FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Collazo, CM Sher, A Elkins, K AF Collazo, CM Sher, A Elkins, K TI The function of myeloid differentiation factor-88 (MyD88) and Toll-like receptors in Francisella tularensis LVS infection in mice SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 US FDA, CBER, Rockville, MD 20852 USA. NIAID, LPD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A454 EP A454 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470602188 ER PT J AU Desai, RI Katz, JL AF Desai, RI Katz, JL TI Discriminative stimulus effects of SKF 82958 SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NIDA, Psychobiol Lab, Intramural Res Program, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A203 EP A203 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470600975 ER PT J AU Deuster, PA Sutton, EE Poth, M Faraday, M Chrousos, G AF Deuster, PA Sutton, EE Poth, M Faraday, M Chrousos, G TI Alprazolam and DHEA effects on neuroendocrine and metabolic responses to exercise: Potentiation of growth hormone secretion SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. NICHD, Pediat & Reprod Endocrinol Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A680 EP A680 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470603261 ER PT J AU Dixon, LB Peters, U Subar, A Schatzkin, A Hayes, R AF Dixon, LB Peters, U Subar, A Schatzkin, A Hayes, R TI Following the US food guide pyramid is associated with reduced risk of colorectal adenoma: Findings from the prostate, lung, colorectal, and ovarian (PLCO) cancer screening trial SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NYU, New York, NY 10012 USA. NCI, DCEG, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A4 EP A4 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470600020 ER PT J AU Dixon, MO Harland, BF Lanza, E Oberleas, D AF Dixon, MO Harland, BF Lanza, E Oberleas, D TI Are dietary phytate (IP6) and fecal phytate related to colorectal polyp formation and recurrence? SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 Howard Univ, Washington, DC 20059 USA. NCI, Basic Res Lab, Bethesda, MD 20892 USA. Texas Tech Univ, Lubbock, TX 79409 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A477 EP A477 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470602299 ER PT J AU Druey, K Johnson, EN Seaholtz, T Waheed, A Suzuki, N Kreutz, B Kozasa, T Jones, TLZ Brown, JH AF Druey, K Johnson, EN Seaholtz, T Waheed, A Suzuki, N Kreutz, B Kozasa, T Jones, TLZ Brown, JH TI RGS16 inhibits signaling through the G alpha 13-Rho axis SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NIAID, Lab Allerg Dis, NIH, Rockville, MD 20852 USA. GlaxoSmithKline, High Throughput Biol, Res Triangle Pk, NC 27709 USA. USCD, Res Triangle Pk, NC USA. NIDDK, NIH, Bethesda, MD USA. UIC Sch Med, 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A219 EP A219 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470601051 ER PT J AU Durbin, JE Gitiban, N Mertz, SE Durbin, RK Hammond, S Johnson, TR AF Durbin, JE Gitiban, N Mertz, SE Durbin, RK Hammond, S Johnson, TR TI Lung eosinophilia in RSV infection is inhibited by IP-10 induction SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 Ohio State Univ, Coll Med & Publ Hlth, Columbus, OH 43205 USA. Childrens Res Inst, Columbus, OH 43205 USA. NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A458 EP A458 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470602207 ER PT J AU Elnekave, E Mentink-Kane, MM Cheever, AW Wynn, TA AF Elnekave, E Mentink-Kane, MM Cheever, AW Wynn, TA TI IL-13R alpha 2 plays a key regulatory role in the sensitization phase of type-2 immune responses SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20814 USA. Biomed Res Inst, Parasit Dis Lab, Rockville, MD 20852 USA. NIH, LPD, Bethesda, MD 20892 USA. RI Wynn, Thomas/C-2797-2011 NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A462 EP A462 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470602228 ER PT J AU Equils, O Bafica, A Lu, DN Baldwin, G AF Equils, O Bafica, A Lu, DN Baldwin, G TI Toll-like receptor (TLR) 4 mediated macrophage tolerance inhibits the HIV replication SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. NIAID, LPD, NIH, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90024 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A453 EP A453 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470602182 ER PT J AU Fan, F Tao, XL Wang, B Wang, SR Zhou, LD Wang, B Lipsky, PE AF Fan, F Tao, XL Wang, B Wang, SR Zhou, LD Wang, B Lipsky, PE TI Pharmacokinetics of [H-3]-triptolide in rats SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NIMH, NIH, Bethesda, MD 20892 USA. Warren G Magnuson Clin Ctr, Clin Pharmacokinet Res Lab, NIH, 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A604 EP A604 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470602899 ER PT J AU Fan, T Muegge, K AF Fan, T Muegge, K TI Role of Lsh in the regulating of gene imprinting SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NCI, SAIC Frederick Inc, Mol Immunoregulat 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A186 EP A186 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470600896 ER PT J AU Finkelstein, LD Schwartzberg, PL AF Finkelstein, LD Schwartzberg, PL TI Tee kinases are required for TCR-mediated upregulation of integrin receptor adhesion SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NHGRI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A53 EP A53 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470600263 ER PT J AU Foley, JF Singh, SP Reiner, JS Farber, JM AF Foley, JF Singh, SP Reiner, JS Farber, JM TI G alpha o, a Gi protein associated with the CNS, is expressed specifically in memory CD4 T cells and can couple to chemokine receptors SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NIAID, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A469 EP A469 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470602259 ER PT J AU Gadina, M Watford, WT Agnello, D Chen, A Hissong, BD Cheng, TP Denise, LI Husa, M Schwartzberg, P O'Shea, JJ AF Gadina, M Watford, WT Agnello, D Chen, A Hissong, BD Cheng, TP Denise, LI Husa, M Schwartzberg, P O'Shea, JJ TI Cybr, a cytokine-induced, PDZ domain-containing adapter molecule which regulates IFN-gamma production SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 Queens Univ Belfast, Belfast BT9 7BL, Antrim, North Ireland. NIAMS, MIIB, NIH, Bethesda, MD USA. NHGRI, NIH, Bethesda, MD 20892 USA. RI Husa, Matthew/G-4850-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A57 EP A57 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470600281 ER PT J AU Galligan, C Matsuyama, W Matsukawa, A Mizuta, H Hodge, DR Howard, OMZ Yoshimura, T AF Galligan, C Matsuyama, W Matsukawa, A Mizuta, H Hodge, DR Howard, OMZ Yoshimura, T TI Upregulated expression and activation of the orphan chemokine receptor, CCRL2, in rheumatoid arthritis SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NCI, Mol Immunoregulat Lab, Frederick, MD 21702 USA. Kumamoto Univ, Dept Pathol & Expt Med, Kumamoto 860, Japan. Kumamoto Univ, Dept Orthopaed, Kumamoto 860, Japan. 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 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A469 EP A469 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470602261 ER PT J AU Gao, ZG Mamedova, LK Jacobson, KA AF Gao, ZG Mamedova, LK Jacobson, KA TI PIT blocks P2Y1 receptor signaling without affecting ADP binding SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NIDDK, LBC, NIH, Bethesda, MD 20892 USA. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A584 EP A584 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470602798 ER PT J AU Gaussin, V Morley, GE Liu, J Cox, L Hong, C Depre, C Myers, D Mishina, Y Behringer, R Hanks, MC Zwijsen, A Huylebroeck, D Fishman, GI Schneider, M Burch, JB Vatner, SF AF Gaussin, V Morley, GE Liu, J Cox, L Hong, C Depre, C Myers, D Mishina, Y Behringer, R Hanks, MC Zwijsen, A Huylebroeck, D Fishman, GI Schneider, M Burch, JB Vatner, SF TI ALK3 is necessary for atrio-ventricular conduction system development SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 Univ Med & Dent New Jersey, New Jersey Med Sch, Newark, NJ 07103 USA. NYU, New York, NY USA. NIH, Res Triangle Pk, NC USA. Univ Louvain, B-3001 Louvain, Belgium. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Procter & Gamble Co, Mason, OH USA. Baylor Coll Med, Houston, TX 77030 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. NR 0 TC 0 Z9 0 U1 0 U2 5 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A403 EP A404 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470601944 ER PT J AU Goldstein, DS Holmes, C Eldadah, B Pechnik, S Sharabi, Y AF Goldstein, DS Holmes, C Eldadah, B Pechnik, S Sharabi, Y TI Cardiovascular dysautonomia in Parkinson's disease: the triple Whammy causing orthostatic hypotension SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NINDS, Clin Neurocardiol Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A662 EP A662 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470603178 ER PT J AU Gruys, ME Back, TC Murphy, WJ Welniak, L Wiltrout, R AF Gruys, ME Back, TC Murphy, WJ Welniak, L Wiltrout, R TI Subclones of a streptozotocin induced renal cell carcinoma as a new model for investigation of treatments for kidney cancer SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 Ctr Canc Res, NCI, Ft Detrick, MD 21702 USA. SAIC Frederick, IRSP, Frederick, MD USA. Univ Nevada, Sch Med, Ctr Canc Res, Reno, NV 89557 USA. CCR, Lab Expt Immunol, NCI, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A61 EP A61 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470600303 ER PT J AU Hartz, AMS Bauer, B Fricker, G Miller, DS AF Hartz, AMS Bauer, B Fricker, G Miller, DS TI Rapid regulation of p-glycoprotein at the blood-brain barrier: role of endothelin-1 SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NIEHS, LPC, Res Triangle Pk, NC 27709 USA. Univ Heidelberg, Inst Pharm & Mol Biotechnol, Heidelberg, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A676 EP A677 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470603246 ER PT J AU Hashimoto, S Hansen, PB Huang, YG Briggs, JP Schnermann, JB AF Hashimoto, S Hansen, PB Huang, YG Briggs, JP Schnermann, JB TI The role of adenosine A2a receptors in the dilatory response to adenosine in mice SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A293 EP A293 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470601412 ER PT J AU Helebo, F Smith, JL Freebern, WJ Haggerty, CM Collins, I Montano, I McNutt, M Westrup, JC Gardner, K AF Helebo, F Smith, JL Freebern, WJ Haggerty, CM Collins, I Montano, I McNutt, M Westrup, JC Gardner, K TI A promoter array database: a bioinformatics approach SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 INCI, NIH, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A202 EP A202 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470600970 ER PT J AU Hendrix, MJC Seftor, EA Meltzer, PS Kirschmann, DA Margaryan, NV Seftor, REB AF Hendrix, MJC Seftor, EA Meltzer, PS Kirschmann, DA Margaryan, NV Seftor, REB TI The epigenetic effect of the tumor cell microenvironment on the transdifferentiation potential of melanoma cells SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 Univ Iowa, Iowa City, IA 52242 USA. NHGRI, Natl Inst Hlth, Canc Genet Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A21 EP A21 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470600103 ER PT J AU Hodge, DL Subleski, JJ Reynolds, DA Buschman, MD Schill, WB Burkett, MW Malyguine, AM Young, H AF Hodge, DL Subleski, JJ Reynolds, DA Buschman, MD Schill, WB Burkett, MW Malyguine, AM Young, H TI The proinflammatory cytokine IL-18 is a potent inhibitor of apoptosis in natural killer cells SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NCI, Expt Immunol Lab, Frederick, MD 21702 USA. USGS, Leetown Sci Ctr, Leetown, WV USA. Sci Applicat Int Corp, Clin Serv Program, Frederick, MD USA. NCI, FCRDC, Expt Immunol Lab, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A475 EP A475 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470602288 ER PT J AU Horai, R Schwartzberg, PL AF Horai, R Schwartzberg, PL TI Roles of Tec family kinases in antigen-specific responses SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NHGRI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A54 EP A55 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470600269 ER PT J AU Houghtling, RA Dombroski, D Labno, CM Birkhardt, JK Schwartzberg, PL AF Houghtling, RA Dombroski, D Labno, CM Birkhardt, JK Schwartzberg, PL TI Cytoskeleton rearrangement to TCR stimulation utilizes Itk as a scaffold SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NHGRI, GDRB, Cell Signaling Sect, NIH, Bethesda, MD 20892 USA. Univ Chicago, Dept Pathol, Chicago, IL 60637 USA. Univ Penn, Dept Pathol, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A54 EP A54 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470600264 ER PT J AU House, RL Cassady, JP Eisen, EJ Eling, TE Odle, J AF House, RL Cassady, JP Eisen, EJ Eling, TE Odle, J TI Functional genomic characterization of polygenic obese mice fed t10, c12 conjugated linoleic acid (CLA) SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 N Carolina State Univ, Raleigh, NC 27695 USA. NIEHS, Lab Mol Carcinogenesis, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A383 EP A384 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470601846 ER PT J AU Huang, JQ Zhu, HM Muegge, K AF Huang, JQ Zhu, HM Muegge, K TI Lsh, an epigenetic regulator at repetitive elements SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NCI, CCR, SAIC, LMI, Ft Detrick, 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A202 EP A202 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470600969 ER PT J AU Iribarren, P Cui, YH Le, YY Ying, GG Zhang, X Gong, WH Wang, JM AF Iribarren, P Cui, YH Le, YY Ying, GG Zhang, X Gong, WH Wang, JM TI Interleukin 4 down-regulates the expression of formyl peptide receptor 2 in LPS- and TNFalpha-activated murine microglia by inhibiting the activation of mitogen activated protein kinases and NFkappaB SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NCI, Mol Immunoregulat Lab, Frederick, MD 21702 USA. Lauzhou Mil Med Univ, Biochem Sect, Lauzhou, Peoples R China. NCI, Expt Immunol Lab, Frederick, MD 21701 USA. SAIC Frederick, Basic Res Program, Frederick, MD USA. RI Zhang, Xia/B-8152-2008 OI Zhang, Xia/0000-0002-9040-1486 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A472 EP A472 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470602274 ER PT J AU Jankovic, D Kullberg, MC Caspar, P Sher, A AF Jankovic, D Kullberg, MC Caspar, P Sher, A TI Parasite induced Th2 polarization is associated with down-regulated dendritic cell function and transient T cell hyporesponsiveness SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A421 EP A421 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470602029 ER PT J AU Justinova, Z Goldberg, SR AF Justinova, Z Goldberg, SR TI Persistent self-administration behavior is maintained by intravenous injections of the endogenous cannabinoid anandamide in squirrel monkeys SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NIDA, Preclin Pharmacol Sect, IRP, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A581 EP A581 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470602786 ER PT J AU Karabekian, Z Pennesi, G Mattapalill, MJ Caspi, R AF Karabekian, Z Pennesi, G Mattapalill, MJ Caspi, R TI Pathogenic epitope(s) of human retinal soluble antigen (h-SAg) in a humanized model of experimental autoimmune uveitis in HLA class-II transgenic mice SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. Natl Inst Canc Res, Dept Innovat Therapies, Genoa, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A38 EP A38 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470600184 ER PT J AU Katz, JL Moulden, E Newman, AH AF Katz, JL Moulden, E Newman, AH TI Dopamine uptake inhibitors: Self-ad ministration and effects on cocaine SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NIDA, Psychobiol Lab, Intramural Res Program, Baltimore, MD 21224 USA. NIDA, Med Chem Sect, Intramural Res Program, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A204 EP A204 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470600980 ER PT J AU Kaviratne, M Cheever, AW Aliberti, J Hieny, S Hesse, M Feng, C Sher, A Sedgwick, J Wynn, T AF Kaviratne, M Cheever, AW Aliberti, J Hieny, S Hesse, M Feng, C Sher, A Sedgwick, J Wynn, T TI CD200 regulates the host response to type-1 and type-2 cytokine-promoting pathogens by modulating macrophage activation SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NIH, Parasit Dis Lab, Bethesda, MD 20814 USA. Biomed Res Inst, Parasit Dis Lab, Rockville, MD USA. Cornell Univ, Ctr Vet Med, Ithaca, NY USA. DNAZ Res Inst, Palo Alto, CA USA. RI Aliberti, Julio/G-4565-2012; Aliberti, Julio/I-7354-2013 OI Aliberti, Julio/0000-0003-3420-8478 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A420 EP A421 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470602027 ER PT J AU Kim, SH Matsuyama, W Yoshimura, T AF Kim, SH Matsuyama, W Yoshimura, T TI TAB1 beta the major TAB1 isoform in human macrophages and dendritic cells, regulates signaling of both discoidine domain receptor 1 (DDR1) and toll-like receptor 4 (TLR4) SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NCI, Mol Immunoregulat Lab, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A52 EP A52 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470600257 ER PT J AU Kim, YJ Kubofcik, J Nutman, TB AF Kim, YJ Kubofcik, J Nutman, TB TI Constitutive expression of mRNA and cell surface Toll-like receptors by eosinophils SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A420 EP A420 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470602025 ER PT J AU Kobrinsky, E Stevens, L Bentil, S Wray, D Soldatov, NM AF Kobrinsky, E Stevens, L Bentil, S Wray, D Soldatov, NM TI Molecular rearrangements associated with voltage gating of the K(v)2.1 channel SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NIA, NIH, Baltimore, MD 21224 USA. Univ Leeds, Sch Biomed Sci, Leeds LS2 9JT, W Yorkshire, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A226 EP A226 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470601085 ER PT J AU Kole, HK Chi, AW Bolland, S AF Kole, HK Chi, AW Bolland, S TI SHIP1 associates with c-Cbl and modulates T cell receptor function SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A56 EP A56 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470600279 ER PT J AU Krebs-Smith, SM Subar, AF Guenther, P Tooze, JA Midthune, D Kipnis, V Dodd, K AF Krebs-Smith, SM Subar, AF Guenther, P Tooze, JA Midthune, D Kipnis, V Dodd, K TI Food propensity questionnaires (FPQs) in the National Health and Nutrition Examination Survey (NHANES): A step in the evolution of usual dietary intake estimation SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NCI, Bethesda, MD 20892 USA. USDA, Alexandria, VA 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A480 EP A480 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470602315 ER PT J AU Laky, KM Fowlkes, BJ AF Laky, KM Fowlkes, BJ TI Presenilin/Notch signals influence thymocyte differentiation, with distinct effects on alpha beta and gamma delta T cell development SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NIAID, LCMI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A48 EP A48 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470600235 ER PT J AU Le Foll, B Sokoloff, P AF Le Foll, B Sokoloff, P TI Nicotine as a treatment in Parkinson's Disease through regulation of BDNF and dopamine D3 receptor expressions SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NIDA, Intramural Res Program, Behav Neurosci Branch, Preclin Pharmacol Sect, Baltimore, MD 21224 USA. INSERM, U573, Paris, France. RI Le Foll, Bernard/K-2952-2014 OI Le Foll, Bernard/0000-0002-6406-4973 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A583 EP A583 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470602793 ER PT J AU Leak, LV Liotta, LA Calvert, VS Petricoin, EF AF Leak, LV Liotta, LA Calvert, VS Petricoin, EF TI Proteomic analysis of lymphangiogenesis SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 Howard Univ, Washington, DC 20059 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. US FDA, Bethesda, MD 20014 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A259 EP A259 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470601247 ER PT J AU Lee, JS Kritchevsky, SB Harris, T Tylavsky, F Rubin, SM Newman, AB AF Lee, JS Kritchevsky, SB Harris, T Tylavsky, F Rubin, SM Newman, AB TI Short-term (6 month) weight change pattern in a biracial sample of community-dwelling older adults SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 Univ Pittsburgh, Pittsburgh, PA 15217 USA. Wake Forest Univ, Winston Salem, NC 27109 USA. NIA, Bethesda, MD 20892 USA. Univ Tennessee, Memphis, TN USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A133 EP A133 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470600647 ER PT J AU Lee, PR Cohen, J Tendi, E Becker, KG DeVries, GH Fields, RD AF Lee, PR Cohen, J Tendi, E Becker, KG DeVries, GH Fields, RD TI Transcriptional profiling in MPNST-derived Schwann cells SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NICHD, SNSDP, NIH, Bethesda, MD 20892 USA. NIA, DNA Array Unit, NIH, Baltimore, MD USA. Hines VA Hosp, Neurol & Res Serv, Hines, IL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A23 EP A23 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470600112 ER PT J AU Lev, A Reiter, Y Bennink, JR Yewdell, JW AF Lev, A Reiter, Y Bennink, JR Yewdell, JW TI Recognition of MHC class I-influenza virus peptide complexes using human recombinant antibodies with TCR-like specificities SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. Technion, Dept Biol, Haifa, Israel. RI yewdell, jyewdell@nih.gov/A-1702-2012 NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A39 EP A39 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470600189 ER PT J AU Li, HF Wojciechowski, W Li, MS Marshall, S Espinoza-Delgado, I AF Li, HF Wojciechowski, W Li, MS Marshall, S Espinoza-Delgado, I TI Bryostatin-1 enhances the expression of IFN-gamma R2 through an ERK-dependent mechanism SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NIA, NIH, Baltimore, MD 21224 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A472 EP A472 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470602276 ER PT J AU Limke, TL Osborne, J Cai, J Miura, T Rao, M AF Limke, TL Osborne, J Cai, J Miura, T Rao, M TI Characterization of neural stem cells in culture reveals similarities and differences across ages and species SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NIH, NIGMS, Baltimore, MD 21224 USA. NIA, NIH, Baltimore, MD 21224 USA. NIA, Neurosci Lab, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A183 EP A183 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470600885 ER PT J AU Liu, KB Abrams, S AF Liu, KB Abrams, S TI Alterations in Fas expression are characteristic of, but not solely responsible for, enhanced metastatic competence SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NCI, Lab Tumor Immunol & Biol, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A66 EP A66 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470600325 ER PT J AU Lougaris, V Jennings, N Fischer, RT Phillips, T Plebani, A Lipsky, P Grammer, AC AF Lougaris, V Jennings, N Fischer, RT Phillips, T Plebani, A Lipsky, P Grammer, AC TI CD154 engagement on tonsillar B cells induces NF-kB activation, Blimp-1 expression and differentiation to plasma cells SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NIAMS, NIH, Bethesda, MD 20892 USA. NIAMS, B Cell Biol Grp, NIH, Bethesda, MD 20892 USA. Untramicro Analyt Immunochem Resource, Bethesda, MD USA. Univ Brescia, Dept Pediat, Brescia, Italy. NIAMS, Autoimmun Branch, NIH, Bethesda, MD USA. RI Plebani, Alessandro/C-8593-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A439 EP A439 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470602117 ER PT J AU Lyles, J Cai, NS Alston, A Hayes, C Thiriet, N Cadet, JL AF Lyles, J Cai, NS Alston, A Hayes, C Thiriet, N Cadet, JL TI Ecstasy (MDMA)-induced changes in gene expression in the rat brainstem SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NIDA, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A583 EP A583 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470602797 ER PT J AU Maasho, K Masilamani, M Basu, S Valas, R Coligan, JE Borrego, F AF Maasho, K Masilamani, M Basu, S Valas, R Coligan, JE Borrego, F TI TCR signals control the cell surface expression of Leukocyte-associated immunoglobulin-like receptor 1 (LAIR-1) in activated T cells SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NIAID, RCBS, LAD, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A55 EP A55 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470600272 ER PT J AU Mamedova, L Gao, ZG Jacobson, KA AF Mamedova, L Gao, ZG Jacobson, KA TI P2Y(12) receptor activation prevents tumor necrosis factor alpha-induced apoptosis SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NIDDK, LBC, Mol Recognit Sect, NIH, Bethesda, MD 20892 USA. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A584 EP A584 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470602799 ER PT J AU Manigold, T Piccirillo, CA Shin, EC Mihalik, K Rice, CM Feinstone, SM Rehermann, B AF Manigold, T Piccirillo, CA Shin, EC Mihalik, K Rice, CM Feinstone, SM Rehermann, B TI CD4+ CD25+ regulatory T cells control effector functions of HCV-specific memory CD8+ T cells in HCV-recovered chimpanzees SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NIDDK, LDS, NIH, Bethesda, MD 20892 USA. NIAID, NIH, Immunol Lab, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Lab Hepatitis Viruses, Bethesda, MD USA. Rockefeller Univ, Ctr Study Hepatitis C, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A85 EP A85 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470600417 ER PT J AU Masilamani, M Sanni, TB Kabat, J Coligan, JE Borrego, F AF Masilamani, M Sanni, TB Kabat, J Coligan, JE Borrego, F TI Exclusion of lipid rafts and decreased mobility of CD94/NKG2A receptors at the inhibitory NK cell synapse SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NIAID, Lab Allerg Dis, Receptor Cell Biol Sect, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A428 EP A428 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470602064 ER PT J AU McKarns, SC Schwartz, RH AF McKarns, SC Schwartz, RH TI Smad3 is required for TGF-beta 1 to inhibit CD4(+) but not CD8(+) T cell proliferation SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A55 EP A55 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470600274 ER PT J AU Melchers, M van Laar, JM Teng, YKO Grivel, JC Margolis, L Lipsky, PE Grammer, AC AF Melchers, M van Laar, JM Teng, YKO Grivel, JC Margolis, L Lipsky, PE Grammer, AC TI Blocking endogenous CD154-CD40 interactions in human tonsillar organ cultures inhibits differentiation of memory B cells to Ig-secreting cells SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NIAMS, Autoimmun Branch, NIH, Bethesda, MD 20893 USA. NICHD, Lab Cellular & Mol Biophys, NIH, Bethesda, MD USA. RI Melchers, Mark/C-1438-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A439 EP A439 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470602118 ER PT J AU Min, B Hu-Li, J Zhu, J Jankovic, D Prout, M Urban, JF LeGros, G Paul, W AF Min, B Hu-Li, J Zhu, J Jankovic, D Prout, M Urban, JF LeGros, G Paul, W TI Basophils are a major IL-4-producers in helminth infection SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Malaghan Inst Med Res, Wellington, New Zealand. USDA, Beltsville Human Nutr Res Ctr, Nutrient Requirements & Funct Lab, Beltsville, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A422 EP A422 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470602034 ER PT J AU Moharram, R Potolicchio, SJ Velicu, I Martin, BM Henkin, RI AF Moharram, R Potolicchio, SJ Velicu, I Martin, BM Henkin, RI TI Growth factor regulation in human olfactory system function: the role of transcranial magnetic stimulation (TCMS) SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NIMH, LNT, Bethesda, MD 20892 USA. George Washington Univ, Dept Neurol, Washington, DC USA. Ctr Mol Nutr & Sensory Disorder, Washington, DC USA. NR 0 TC 3 Z9 3 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A201 EP A201 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470600962 ER PT J AU Mongini, P Kalled, S Fattah, R Inman, J AF Mongini, P Kalled, S Fattah, R Inman, J TI Human B cell clonal expansion is synergistically augmented upon BCR coligation with CD21 in the presence of IL-4 and BAFF SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NYU Med Ctr, New York, NY 10003 USA. Biogen Idee, Cambridge, MA USA. 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A464 EP A464 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470602234 ER PT J AU Montano, I Freebern, WJ Smith, JL Collins, I Haggerty, CM McNutt, M Dzekunova, I Peterson, D Kawasaki, E Gardner, K AF Montano, I Freebern, WJ Smith, JL Collins, I Haggerty, CM McNutt, M Dzekunova, I Peterson, D Kawasaki, E Gardner, K TI Characterizing p300 function in vivo by profiling drug influenced transcriptional responses SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NCI, NIH, Bethesda, MD 20892 USA. NCI, NCI MicroArray Lab, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A203 EP A203 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470600972 ER PT J AU Murphy, DD AF Murphy, DD TI New views of the neuropathology of Parkinson's disease SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NINDS, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A404 EP A404 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470601946 ER PT J AU Newby, PK Muller, D Tucker, KL AF Newby, PK Muller, D Tucker, KL TI Validation of empirically derived eating patterns with plasma lipid biomarkers: comparison of cluster and factor analysis methods SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr Aging, Boston, MA 02111 USA. NIA, NIH, Baltimore, MD 21224 USA. RI Tucker, Katherine/A-4545-2010 NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A115 EP A115 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470600561 ER PT J AU Nitto, T Dyer, KD Bystrom, J Mejia, RA Wynn, TA Rosenberg, HF AF Nitto, T Dyer, KD Bystrom, J Mejia, RA Wynn, TA Rosenberg, HF TI IL-5 dependent regulation of eosinophil ribonuclease gene expression SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. NIAID, Parasit Dis Lab, NIH, Bethesda, MD USA. RI Wynn, Thomas/C-2797-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A416 EP A416 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470602007 ER PT J AU Ogawa, J Kurihara, H Tada, N Sasaki, T Ichimura, K Sakai, T Morgan, G Yamada, Y Arikawa-Hirasawa, E AF Ogawa, J Kurihara, H Tada, N Sasaki, T Ichimura, K Sakai, T Morgan, G Yamada, Y Arikawa-Hirasawa, E TI The distinct role of laminin-1 in early mouse development SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 Juntendo Univ, Sch Med, Tokyo 1138421, Japan. Max Planck Inst Biochem, Dept Mol Med, Munich, Germany. NIDCR, CDBRB, NIH, Bethesda, MD USA. RI Ogawa, Junko/I-7619-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A386 EP A386 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470601857 ER PT J AU Onaivi, ES Mora, Z Perchuk, A Brandoni, C Leonard, CM Uhl, GR Akinshola, BE AF Onaivi, ES Mora, Z Perchuk, A Brandoni, C Leonard, CM Uhl, GR Akinshola, BE TI An endocannabinoid hypothesis of substance abuse SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NIDA, WPUNJ, NRI, NIH, Haledon, NJ 07508 USA. William Paterson Univ, Wayne, NJ USA. NIDA, Neurobiol Branch, Baltimore, MD USA. Howard Univ, Washington, DC 20059 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A581 EP A581 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470602784 ER PT J AU Pacher, P Mabley, JG Post, H Liaudet, L Batkai, S Kunos, G Szabo, C AF Pacher, P Mabley, JG Post, H Liaudet, L Batkai, S Kunos, G Szabo, C TI Characterization of cardiac function in eNOS and iNOS knockout mice using new Millar pressure-volume conductance system SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 Inotek Pharmaceut Corp, Beverly, MA 01915 USA. NIAAA, NIH, Bethesda, MD USA. RI Batkai, Sandor/G-3889-2010; Batkai, Sandor/H-7983-2014; Liaudet, Lucas/E-1322-2017 OI Liaudet, Lucas/0000-0003-2670-4930 NR 0 TC 1 Z9 1 U1 0 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A274 EP A274 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470601318 ER PT J AU Packer, RK Bender, KT Terris, JM Turban, S Pamnani, MB Schooley, JF Fenton, RA Knepper, MA AF Packer, RK Bender, KT Terris, JM Turban, S Pamnani, MB Schooley, JF Fenton, RA Knepper, MA TI Angiotensin II regulates proximal tubule sodium transporter distribution and expression in male rats SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 George Washington Univ, Washington, DC 20052 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. NHLBI, LKEM, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A730 EP A730 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470603501 ER PT J AU Porter, MA Roberts, MA Wu, ZQ Kelly, J Siegel, RM AF Porter, MA Roberts, MA Wu, ZQ Kelly, J Siegel, RM TI A novel pathway of post-activation T cell survival blocked by v-FLIP SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NIAMS, NIH, Bethesda, MD 20892 USA. NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A56 EP A56 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470600276 ER PT J AU Qi, ZH Morrow, JD Hao, CM Langenbach, R Breyer, MD AF Qi, ZH Morrow, JD Hao, CM Langenbach, R Breyer, MD TI Tissue heterogeneity of angiotensin II effects on prostaglandin (PG) synthesis SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 Vanderbilt Univ, Nashville, TN 37232 USA. NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A687 EP A687 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470603297 ER PT J AU Qiao, HH Beaven, M AF Qiao, HH Beaven, M TI Suppression of toll-like receptor (TLR)-mediated activation of mast cells by dexamethasone SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A432 EP A433 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470602086 ER PT J AU Radimer, K Bindewald, B Picciano, MF Swanson, C AF Radimer, K Bindewald, B Picciano, MF Swanson, C TI Survey methodology for dietary supplements: using NHANES data in conjunction with less detailed collection methods to assign nutrient estimates to reported supplements SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 DHANES, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA. ODS, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A112 EP A112 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470600546 ER PT J AU Radimer, K Bindewald, B Hughes, J Ervin, B Swanson, C Picciano, MF AF Radimer, K Bindewald, B Hughes, J Ervin, B Swanson, C Picciano, MF TI Factors associated with dietary supplement use by adults, NHANES 1999-2000 SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 Natl Ctr Hlth Stat, DHANES, Hyattsville, MD 20782 USA. NIH, ODS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A5 EP A5 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470600025 ER PT J AU Rand-Giovanetti, D Ling, SM Taub, DD Abernethy, DR AF Rand-Giovanetti, D Ling, SM Taub, DD Abernethy, DR TI Biomarkers in animal models of arthritis and physical inactivity SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 Mt Hebron High Sch, Ellicott City, MD 21042 USA. NIA, Clin Res Branch, Baltimore, MD 21224 USA. NIA, NIH, Gerontol Res Ctr, Baltimore, MD 21224 USA. NIA, Clin Invest Lab, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A690 EP A690 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470603310 ER PT J AU Rao, MS Liu, Y AF Rao, MS Liu, Y TI Generation of astrocytes during development SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NIA, Neurosci Lab, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A400 EP A400 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470601928 ER PT J AU Reedy, J Haines, PS Campbell, MK AF Reedy, J Haines, PS Campbell, MK TI Dietary differences among categories of dietary supplement use in colorectal cancer survivors and a comparison population SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NCI, Bethesda, MD USA. Univ N Carolina, Sch Publ Hlth, Chapel Hill, NC 27515 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A477 EP A477 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470602300 ER PT J AU Reiman, RM Hari, DM Mentink-Kane, MM Rosenberg, HF Cheever, AW Wynn, TA AF Reiman, RM Hari, DM Mentink-Kane, MM Rosenberg, HF Cheever, AW Wynn, TA TI The role of IL-5 in cytokine responses and granuloma formation during Schistosoma mansoni infection SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NIAID, LPD, NIH, Bethesda, MD 20892 USA. NIAID, LHD, GIS, NIH, Bethesda, MD 20892 USA. BRI, Schistosomiasis Lab, Rockville, MD USA. RI Wynn, Thomas/C-2797-2011 NR 0 TC 0 Z9 0 U1 0 U2 4 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A90 EP A91 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470600445 ER PT J AU Rodriguez-Galan, MC Young, HA AF Rodriguez-Galan, MC Young, HA TI The effect of interleukin (IL)-12 or IL-12+IL-18 on murine thymic and splenic lymphocytes SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NCI, 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A466 EP A466 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470602245 ER PT J AU Schmit, TE Voyich, JM DeLeo, FR AF Schmit, TE Voyich, JM DeLeo, FR TI Modulation of surface protein expression during phagocytosis-induced apoptosis in human neutrophils SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 Rocky Mt Labs, Lab Human Bacterial Pathogenesis, NIH, Hamilton, MT 59840 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A35 EP A35 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470600168 ER PT J AU Schnor, N Shannon, T Knepper, M Packer, RK AF Schnor, N Shannon, T Knepper, M Packer, RK TI Carbenoxolone inhibition of 11 beta-hydroxysteroid dehydrogenase, type 2, increases blood pressure and abundance of aldosterone-regulated sodium transporters in the rat kidney SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 George Washington Univ, Washington, DC 20052 USA. NHLBI, Lab Kidney & Electrolyte Metab, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A732 EP A732 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470603510 ER PT J AU Seifert, U Liermann, H Racanelli, V Halenius, A Wiese, M Wedemeyer, H Ruppert, T Rispeter, K Henklein, P Sijts, A Hengel, H Kloetzel, P Rehermann, B AF Seifert, U Liermann, H Racanelli, V Halenius, A Wiese, M Wedemeyer, H Ruppert, T Rispeter, K Henklein, P Sijts, A Hengel, H Kloetzel, P Rehermann, B TI Hepatitis C virus mutation affects intracellular proteasomal epitope processing in vitro and in vivo SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 Humboldt Univ, Charity, Dept Biochem, D-10117 Berlin, Germany. Hannover Med Sch, Dept Gastroenterol, Hannover, Germany. NIH, Liver Dis Sect, Bethesda, MD 20892 USA. Robert Koch Inst, D-1000 Berlin, Germany. Klinikum St Georg, Leipzig, Germany. Univ Essen Gesamthsch, Inst Virol, D-4300 Essen 1, Germany. NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A458 EP A458 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470602206 ER PT J AU Shanker, A Schmitt-Verhulst, AM Inderberg-Suso, EM AF Shanker, A Schmitt-Verhulst, AM Inderberg-Suso, EM TI Monoclonal CD8 T lymphocytes recognizing a self tumor associated antigen provide resistance to tumor development in vivo in synergy with NK cells SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NCI, Basic Res Program, SAIC Frederick Inc, Frederick, MD 21702 USA. Ctr Immunol Marseille Luminy, Lab T Cell Activat & Tolerance, Marseille, France. NR 0 TC 2 Z9 2 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A83 EP A83 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470600409 ER PT J AU Shapira, E Kunihiro, Y Zhou, YJ O'Shea, JJ Ben-Sasson, SZ AF Shapira, E Kunihiro, Y Zhou, YJ O'Shea, JJ Ben-Sasson, SZ TI The role of JAK3 in macrophage activation by LPS SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 Hebrew Univ Jerusalem, Hadassah Med Sch, Hadassah Med Ctr, Lautenberg Ctr Gen & Tumor Immunol, IL-91120 Jerusalem, Israel. NIH, Mol Immunol & Inflammat Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A465 EP A465 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470602242 ER PT J AU Sharabi, Y Dendi, R Holmes, C Goldstein, DS AF Sharabi, Y Dendi, R Holmes, C Goldstein, DS TI Baroreflex failure as a late sequela of neck irradiation SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 Chaim Sheba Med Ctr, Hypertens Unit, IL-52621 Tel Hashomer, Israel. NINDS, Clin Neurocardiol Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A662 EP A662 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470603179 ER PT J AU Shin, EC Protzer, U Untergasser, A Hasselschwert, D Rice, CM Feinstone, SM Rehermann, B AF Shin, EC Protzer, U Untergasser, A Hasselschwert, D Rice, CM Feinstone, SM Rehermann, B TI Effect of liver-directed IFN-gamma gene delivery in chronic hepatitis C virus infection SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NIDDK, Liver Dis Sect, NIH, Bethesda, MD 20892 USA. Univ Cologne, Ctr Mol Med, Cologne, Germany. Univ Louisiana, New Iberia Res Ctr, Lafayette, LA USA. Rockefeller Univ, Ctr Study Hepatitis C, New York, NY USA. US FDA, Ctr Biol Evaluat & Res, Lab Hepatitis Viruses, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A91 EP A92 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470600450 ER PT J AU Shizukuda, Y Hwang, PM Birdsall, CW Plehn, JF Sachdev, V AF Shizukuda, Y Hwang, PM Birdsall, CW Plehn, JF Sachdev, V TI Feasibility of pulsed tissue Deoppler velocity imaging in assessing systolic function of murine global heart failure SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NHLBI, Cardiovasc Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A644 EP A644 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470603093 ER PT J AU Singh, SP Foley, JF Liao, F Farber, JM AF Singh, SP Foley, JF Liao, F Farber, JM TI Mutagenesis of unique sequences in CXCR6 reveal novel features of the critical second intracellular loop in chemokine receptor signaling SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NIAID, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A467 EP A468 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470602253 ER PT J AU Sinha, RK Mage, RG AF Sinha, RK Mage, RG TI Developing neonatal rabbit appendix, a primary lymphoid organ, is seeded by immature blood-borne B cells: evidence for roles for CD62L/PNAd, CCR7/CCL21, alfa4beta1 and LFA-1 SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A70 EP A70 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470600346 ER PT J AU Solinas, M Panlilio, L Goldberg, SR AF Solinas, M Panlilio, L Goldberg, SR TI Exposure to delta-9-THC increases subsequent heroin-taking but not heroin's reinforcing efficacy: a self-administration study in rats SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NIDA, Preclin Pharmacol Sect, NIH, DHHS, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A581 EP A581 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470602785 ER PT J AU Song, K Rabin, RL Hill, BJ De Rosa, S Perfetto, SP Reiner, JS Zhang, HWH Foley, JF Marmol, J Douek, DC Roederer, M Farber, JM AF Song, K Rabin, RL Hill, BJ De Rosa, S Perfetto, SP Reiner, JS Zhang, HWH Foley, JF Marmol, J Douek, DC Roederer, M Farber, JM TI CXCR3 and CCR4 reveal polarized early central memory CD4+T cells in humans SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NIAID, LCI, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. NIAID, VRC, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A467 EP A467 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470602251 ER PT J AU Souto-Carneiro, MM Fritsch, R Yanovski, J Lipsky, PE AF Souto-Carneiro, MM Fritsch, R Yanovski, J Lipsky, PE TI Abnormalities in V(D)J rearrangements in patients with X-linked hyper-IgM ectodermal dysplasia syndrome indicate a requirement for the Ikk(gamma)-dependent signaling pathway in V(D)J recombination SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NIAMS, NIH, Bethesda, MD 20892 USA. NICHD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A79 EP A79 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470600389 ER PT J AU Stephens, G McHugh, R Whitters, M Brinster, C Young, D Collins, M Shevach, E AF Stephens, G McHugh, R Whitters, M Brinster, C Young, D Collins, M Shevach, E TI Regulation of CD4+CD25+ suppressor T cell function by GITR/GITR-L SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NIAID, NIH, Bethesda, MD 20892 USA. Wellington Sch Med, Malaghan Inst Med Res, Bethesda, MD USA. Wyeth Res, Inst Genet, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A86 EP A86 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470600421 ER PT J AU Stolzenberg-Solomon, RZ Mason, JB Poirier, LA Choi, SW Selhub, J Crott, J Rothman, N Sinha, R AF Stolzenberg-Solomon, RZ Mason, JB Poirier, LA Choi, SW Selhub, J Crott, J Rothman, N Sinha, R TI Evaluation of integrative biochemical and molecular biomarkers of one-carbon metabolism in healthy SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NCI, DCEG, Rockville, MD 20852 USA. Tufts Univ, HNRC, Boston, MA 02111 USA. US FDA, NCTR, Jefferson, AR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A110 EP A111 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470600539 ER PT J AU Striebel, JF Hasenkrug, KJ AF Striebel, JF Hasenkrug, KJ TI Identification and analysis of the Rfv3 genotype and determination of its mechanism of resistance to retrovirus induced disease SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH,Corvallis High Sch, Corvallis, MT 59828 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A34 EP A34 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470600165 ER PT J AU Subar, AF Dodd, K Thompson, FE Kipnis, V Midthune, D Krebs-Smith, SM AF Subar, AF Dodd, K Thompson, FE Kipnis, V Midthune, D Krebs-Smith, SM TI What, exactly, is the food propensity questionniare?\ SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A481 EP A481 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470602316 ER PT J AU Subbaraol, K Shao, WH Gao, JL Murphy, PM Haribabu, B AF Subbaraol, K Shao, WH Gao, JL Murphy, PM Haribabu, B TI Distinct roles for leukotriene B-4 and n-formyl peptide receptors in host response to infection in mice SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 Univ Louisville, Hlth Sci Ctr, James Graham Brown Canc Ctr, Louisville, KY 40202 USA. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A468 EP A469 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470602258 ER PT J AU Sutton, EE Pillemer, S Chrousos, G Deuster, PA AF Sutton, EE Pillemer, S Chrousos, G Deuster, PA TI Deficient neuroendocrine, metabolic, and physiologic responses to exercise stress in women with fibromyalgia (FMS) SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. NIDCR, Sjogrens Syndrome Clin, Bethesda, MD USA. NICHD, Pediat & Reprod Endocrinol Branch, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A752 EP A752 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470603605 ER PT J AU Tailor, PB Gabriele, L Tamura, T Ozato, K AF Tailor, PB Gabriele, L Tamura, T Ozato, K TI Role of IRF-8/ICSBP in type I interferon induction in dendritic cells SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NICHHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. Ist Super Sanita, Virol Lab, I-00161 Rome, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A463 EP A463 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470602233 ER PT J AU Talaat, KR Domenech, P Nutman, TB AF Talaat, KR Domenech, P Nutman, TB TI Live microfilariae alter the innate response to infectious Mtb in vitro SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NIH, LPD, Bethesda, MD 20892 USA. NIH, LHD, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A88 EP A89 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470600435 ER PT J AU Tooze, JA Dodd, KN Midthune, D Krebs-Smith, SM Subar, AF Kipnis, V AF Tooze, JA Dodd, KN Midthune, D Krebs-Smith, SM Subar, AF Kipnis, V TI Estimating the distribution of usual intake of episodically consumed foods using two 24-hour recalls and a food propensity questionnaire SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NCI, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A481 EP A481 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470602317 ER PT J AU Tzeng, SJ Pierce, S AF Tzeng, SJ Pierce, S TI Fc gamma RIIB1 mediates the negative selection of B lymphocytes in germinal centers SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NIAID, NIH, Immunogenet Lab, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A82 EP A83 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470600405 ER PT J AU Varnai, P Hunyady, L Balla, T AF Varnai, P Hunyady, L Balla, T TI Studies on the local regulatory aspects of inositol(1,4,5)trisphosphate (InsP3) and Ca2+signaling using InsP3-binding proteins targeted to specific intracellular compartments SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Annual Meeting CY APR 17-21, 2004 CL Washington, DC C1 Semmelweis Univ, Dept Physiol, H-1088 Budapest, Hungary. NICHD, ERRB, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A309 EP A309 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470601488 ER PT J AU Venegas, AM Cannons, J Jankovic, D Sommers, C Love, P Sher, A Schwartzberg, P AF Venegas, AM Cannons, J Jankovic, D Sommers, C Love, P Sher, A Schwartzberg, P TI T(h)2 responses in ITK-/- mice over-expressing TXK/RLK SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NHGRI, GDRB, NIH, Bethesda, MD 20892 USA. NAIAD, NIH, Bethesda, MD USA. NCI, NIH, Bethesda, MD 20892 USA. NICHD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A57 EP A57 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470600284 ER PT J AU Vistica, BP Chen, J Takase, H Ham, DI Wawrousek, E Durum, S Chan, CC Gery, I AF Vistica, BP Chen, J Takase, H Ham, DI Wawrousek, E Durum, S Chan, CC Gery, I TI Localized T-lymphoid infiltration in eyes of transgenic mice expressing IL-7 selectively in their lens SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NEI, LI, NIH, Bethesda, MD 20892 USA. NEI, LMDB, NIH, Bethesda, MD 20892 USA. NCI, FCRDC, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A449 EP A450 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470602167 ER PT J AU Ward, JM Smith, CD Lyons, H Anver, M Haines, DC Herring, J Hollingshead, M Gorelick, P AF Ward, JM Smith, CD Lyons, H Anver, M Haines, DC Herring, J Hollingshead, M Gorelick, P TI Fatty liver hepatitis in SCID/NCr mice naturally infected with mouse hepatitis coronavirus SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NCI, Frederick, MD 21702 USA. NCI, SAIC, Frederick, MD 21702 USA. NCI, SAIC, LASP, Frederick, MD 21702 USA. NCI, Biol Testing Branch, 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A557 EP A558 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470602675 ER PT J AU Watanabe, M Yazawa, H Back, T Subleski, J Wiltrout, R Ortaldo, J AF Watanabe, M Yazawa, H Back, T Subleski, J Wiltrout, R Ortaldo, J TI Anti-metastatic effects of interleukin-I2 gene therapy SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NCI CCR, Lab Expt Immunol, Frederick, MD 21702 USA. SAIC, Lab Expt Immunol, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A62 EP A62 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470600306 ER PT J AU Weinstein, BM AF Weinstein, BM TI Imaging developing blood vessels in the zebrafish SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NICHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A1 EP A1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470600007 ER PT J AU Weinstein, SJ Hartman, TJ Stolzenberg-Solomon, R Pietinen, P Barrett, MJ Taylor, PR Virtamo, J Albanes, D AF Weinstein, SJ Hartman, TJ Stolzenberg-Solomon, R Pietinen, P Barrett, MJ Taylor, PR Virtamo, J Albanes, D TI Prostate cancer risk and one-carbon metabolism dietary and serum factors SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NCI, Nutr Epidemiol Branch, Bethesda, MD 20892 USA. Penn State Univ, Dept Nutr, University Pk, PA USA. Natl Publ Hlth Inst, Dept Epidemiol & Hlth Promot, Helsinki, Finland. IMS Inc, Silver Spring, MD USA. DHHS, Ctr Canc Res, NCI, NIH, Rockville, MD USA. RI Albanes, Demetrius/B-9749-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A381 EP A381 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470601835 ER PT J AU Weiss, SJ Kearns, DN Schindler, CW Panlilio, LV AF Weiss, SJ Kearns, DN Schindler, CW Panlilio, LV TI Conditioned inhibition of drug self-administration SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 American Univ, Dept Psychol, Washington, DC 20016 USA. NIDA, Intramural Res Program, NIH, DHHS, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A205 EP A205 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470600985 ER PT J AU Westrup, JC Smith, JL Freebern, WJ Haggerty, CM Collins, I Montano, I Helebo, F Gardner, K AF Westrup, JC Smith, JL Freebern, WJ Haggerty, CM Collins, I Montano, I Helebo, F Gardner, K TI Defining functional roles of HDAC inhibitors by profiling of transcriptional targets SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NCI, NIH, Ctr Adv Technol, Lab Receptor Biol & Gene Express, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A202 EP A202 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470600968 ER PT J AU Wilson, EH Wille, U Hunter, CA AF Wilson, EH Wille, U Hunter, CA TI The role of IL-10 during chronic toxoplasma infection SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 Univ Penn, Dept Pathobiol, Philadelphia, PA 19103 USA. NIAID, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A440 EP A440 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470602123 ER PT J AU Wright, ME Michaud, DS Pietinen, P Taylor, PR Virtamo, J Albanes, D AF Wright, ME Michaud, DS Pietinen, P Taylor, PR Virtamo, J Albanes, D TI Effect of estimated renal net acid excretion (NAE) on bladder cancer risk in a cohort of male smokers SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NCI, Div Canc Epidemiol & Genet, DHHS, NIH, Rockville, MD 20852 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Natl Publ Hlth Inst, Dept Epidemiol & Hlth Promot, Helsinki, Finland. NCI, Canc Res Ctr, DHHS, NIH, Rockville, MD USA. RI Michaud, Dominique/I-5231-2014; Albanes, Demetrius/B-9749-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A477 EP A477 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470602301 ER PT J AU Wu, ZQ Roberts, M Porter, MA Wherry, J Ahmed, R Siegel, RM AF Wu, ZQ Roberts, M Porter, MA Wherry, J Ahmed, R Siegel, RM TI vFLIP blocks the generation of functional memory CD8 cells SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NIH, Bethesda, MD 20892 USA. NIAMS, NIH, Bethesda, MD 20892 USA. Emory Univ, Vaccine Ctr, Atlanta, GA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A437 EP A438 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470602111 ER PT J AU Wynn, TA Hesse, M Sandler, NG Kaviratne, M Hoffmann, KF Chiaramonte, MG Reiman, R Cheever, AW Sypek, JP Mentink-Kane, MM AF Wynn, TA Hesse, M Sandler, NG Kaviratne, M Hoffmann, KF Chiaramonte, MG Reiman, R Cheever, AW Sypek, JP Mentink-Kane, MM TI P selectin suppresses hepatic inflammation and fibrosis in mice by regulating IFN-gamma and the IL-13 decoy receptor SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NIH, Parasit Dis Lab, Bethesda, MD 20892 USA. Wyeth Pharmaceut, Cambridge, MA USA. NIAID, Parasit Dis Lab, Bethesda, MD 20892 USA. RI Wynn, Thomas/C-2797-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A442 EP A442 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470602133 ER PT J AU Yang, GB Obiakor, H Sinha, R Newman, B Mage, R AF Yang, GB Obiakor, H Sinha, R Newman, B Mage, R TI Cloning of rabbit activation-induced deaminase and localization in developing appendix and immunized spleen SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC 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 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A78 EP A79 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470600386 ER PT J AU Yang, YH Weng, NP AF Yang, YH Weng, NP TI Expression of annexin Al in resting and activated CD4+T cells SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NIA, Immunol Lab, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A54 EP A54 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470600266 ER PT J AU Young, NF Bi, YM Wadhwa, S Chen, XD AF Young, NF Bi, YM Wadhwa, S Chen, XD TI Small leucine rich proteoglcyans: Extracellular matrix regulatory molecules that control proliferation, differentiation and apoptosis in skeletal tissue SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A405 EP A405 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470601950 ER PT J AU Yu, LJ Cannons, JL Crotty, S Siminovitch, KA Ahmed, R Schwartzberg, PL AF Yu, LJ Cannons, JL Crotty, S Siminovitch, KA Ahmed, R Schwartzberg, PL TI The role of SAP in T cell-B cell collaboration SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NHGRI, NIH, Bethesda, MD 20892 USA. Emory Univ Med, Dept Microbiol & Immunol, Atlanta, GA USA. Univ Toronto, Dept Med Genet & Microbiol, Toronto, ON, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A435 EP A435 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470602098 ER PT J AU Zhao, CWL Andrews, KW Holden, JM Brandt, MM Spease, C Dwyer, J Picciano, MF AF Zhao, CWL Andrews, KW Holden, JM Brandt, MM Spease, C Dwyer, J Picciano, MF TI Caffeine containing dietary supplements SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. ARS, Nutrient Data Lab, USDA, Beltsville, MD 20705 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A128 EP A128 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470600620 ER PT J AU Zhu, H Huang, J Muegge, K AF Zhu, H Huang, J Muegge, K TI Mouse conditional knockout of the epigenetic regulator, Lsh SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2004 Meeting CY APR 17-21, 2004 CL Washington, DC C1 NCI, SAIC, LMI, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 23 PY 2004 VL 18 IS 4 SU S BP A186 EP A186 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 806ZA UT WOS:000220470600897 ER PT J AU Gorospe, JR Singhal, BS Kainu, T Wu, F Stephan, D Trent, J Hoffman, EP Naidu, S AF Gorospe, JR Singhal, BS Kainu, T Wu, F Stephan, D Trent, J Hoffman, EP Naidu, S TI Indian Agarwal megalencephalic leukodystrophy with cysts is caused by a common MLC1 mutation SO NEUROLOGY LA English DT Article ID MILD CLINICAL COURSE; SUBCORTICAL CYSTS; LEUKOENCEPHALOPATHY AB Background: A distinct clinical syndrome characterized by megalencephaly, mild to moderate cognitive decline, slowly progressive spasticity, ataxia, occasional seizures, and extensive white matter changes with temporal cysts by imaging studies has been described in a particular ethnic group (Agarwals) in India. This disorder is very similar to megalencephalic leukoencephalopathy with subcortical cysts (MLC), a newly characterized leukodystrophy whose molecular basis was recently shown to be mutations in a gene (KIAA0027) that has been renamed MLC1. Objective: To determine if this disorder among the Agarwals is due to mutations in MLC1 by a mutation screening study conducted on affected Agarwal patients. Methods: Genomic DNA from these Indian leukodystrophy patients was screened for mutations in the entire coding region, including the exon-intron boundaries, of the MLC1 gene. Results: Thirty-three affected individuals whose clinical and imaging presentations were consistent with MLC were screened. All were from northern India and included 31 known Agarwals, 1 non-Agarwal, and 1 adopted patient whose ethnicity is unknown. All 31 Agarwal patients tested positive for a homozygous insertion of a cytosine in exon 2. The adopted patient was homozygous for A157E. No mutation in the coding region was found in the non-Agarwal patient. Conclusions: Indian patients with megalencephaly and MRI changes that show extensive white matter changes with temporal cysts should raise suspicion for MLC. Members of the Agarwal ethnic group affected with the disorder present with a mildly progressive course and show a common mutation (320insC) in the MLC1 gene, suggesting a founder effect. C1 Childrens Natl Med Ctr, Med Genet Res Ctr, Washington, DC 20010 USA. NHGRI, NIH, Bethesda, MD 20892 USA. Kennedy Krieger Inst, Neurogenet Unit, Baltimore, MD USA. Bombay Hosp & Med Res Ctr, Dept Neurol, Inst Med Sci, Bombay, Maharashtra, India. RP Gorospe, JR (reprint author), Childrens Natl Med Ctr, Med Genet Res Ctr, 111 Michigan Ave NW, Washington, DC 20010 USA. EM rgorospe@cnmcresearch.org NR 13 TC 37 Z9 37 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAR 23 PY 2004 VL 62 IS 6 BP 878 EP 882 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 805KN UT WOS:000220365300008 PM 15037685 ER PT J AU Ruggieri, PM Najm, I Bronen, R Campos, M Cendes, F Duncan, JS Weiser, HG Theodore, WH AF Ruggieri, PM Najm, I Bronen, R Campos, M Cendes, F Duncan, JS Weiser, HG Theodore, WH TI Neuroimaging of the cortical dysplasias SO NEUROLOGY LA English DT Article; Proceedings Paper CT 11th International Cleveland Clinic-Bethel Epilepsy Symposium CY JUN, 2000 CL Cleveland, OH ID ATTENUATED INVERSION-RECOVERY; TUBEROUS SCLEROSIS; PARTIAL EPILEPSY; MR; MALFORMATIONS; SEQUENCE; CORTEX C1 Cleveland Clin Fdn, Dept Neuroradiol, Cleveland, OH 44195 USA. Cleveland Clin Fdn, Dept Neurol, Cleveland, OH 44195 USA. Yale Univ, Sch Med, Dept Diagnost Radiol & Neurosurg, New Haven, CT USA. Pontificia Univ Catolica Chile, Dept Neurocirugia, Santiago, Chile. UNICAMP, FCM, Dept Neurol, Campinas, SP, Brazil. UCL, Inst Neurol, Dept Clin & Expt Epilepsy, London, England. Univ Spital Zurich, Neurol Klin, Abt Epileptol & Elektronenzephalog, Zurich, Switzerland. NINDS, Clin Epilepsy Sect, NIH, Bethesda, MD 20892 USA. RP Najm, I (reprint author), 9500 Euclid Ave,S51, Cleveland, OH 44195 USA. EM najmi@ccf.org RI Cendes, Fernando/C-1301-2012 OI Cendes, Fernando/0000-0001-9336-9568 NR 26 TC 18 Z9 19 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAR 23 PY 2004 VL 62 IS 6 SU 3 BP S27 EP S29 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 807IM UT WOS:000220495200006 PM 15037675 ER PT J AU Sakchaisri, K Asano, S Yu, LR Shulewitz, MJ Park, CJ Park, JE Cho, YW Veenstra, TD Thorner, J Lee, KS AF Sakchaisri, K Asano, S Yu, LR Shulewitz, MJ Park, CJ Park, JE Cho, YW Veenstra, TD Thorner, J Lee, KS TI Coupling morphogenesis to mitotic entry SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE Cdk1 regulation; mitotic progression; G(2)/M transtion; Saccharomyces cerevisiae ID SACCHAROMYCES-CEREVISIAE; PROTEIN-KINASE; BUDDING-YEAST; CELL-CYCLE; SWE1P DEGRADATION; TYROSINE PHOSPHORYLATION; NEGATIVE REGULATION; DNA-REPLICATION; CHECKPOINT; LOCALIZATION AB In eukaryotes, cyclin B-bound cyclin-dependent protein kinase 1 promotes mitotic entry but is held in check, in part, by Wee1 protein kinase. Timely mitotic entry in budding yeast requires inactivation of Swell (Wee1 ortholog). Perturbations of the septin collar at the bud neck lead to Swe1 stabilization, delaying the G(2)/M transition. Swell is recruited to the neck and hyperphosphorylated before ubiquitin-mediated degradation. Hsl1 kinase (Nim1 ortholog), a negative regulator of Wee1, is required for efficient Swell localization at the neck but seems not to phosphorylate Swe1. Here, we show that two other kinases targeted sequentially to the neck, Cla4/PAK and Cdc5/Polo, are responsible for stepwise phosphorylation and down-regulation of Swell. This mechanism links assembly of a cellular structure to passage into mitosis. C1 NCI, Ctr Canc Res, Lab Metab, NIH, Bethesda, MD 20892 USA. NCI, Mass Spectrometry Ctr, Ft Detrick, MD 21702 USA. Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. Mahidol Univ, Fac Sci, Dept Pharmacol, Bangkok 10400, Thailand. RP Lee, KS (reprint author), NCI, Ctr Canc Res, Lab Metab, NIH, 9000 Rockville Pike,Bldg 37,Room 3118, Bethesda, MD 20892 USA. EM kyunglee@pop.nci.nih.gov RI Cho, Young-Wook /F-8269-2011 FU NIGMS NIH HHS [GM 21841, R01 GM021841] NR 42 TC 88 Z9 90 U1 1 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 23 PY 2004 VL 101 IS 12 BP 4124 EP 4129 DI 10.1073/pnas.0400641101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 806ZQ UT WOS:000220472200026 PM 15037762 ER PT J AU Baric, I Fumic, K Glenn, B Cuk, M Schulze, A Finkelstein, JD James, SJ Mejaski-Bosnjak, V Pazanin, L Pogribny, IP Rados, M Sarnavka, V Scukanec-Spoljar, M Allen, RH Stabler, S Uzelac, L Vugrek, O Wagner, C Zeisel, S Mudd, SH AF Baric, I Fumic, K Glenn, B Cuk, M Schulze, A Finkelstein, JD James, SJ Mejaski-Bosnjak, V Pazanin, L Pogribny, IP Rados, M Sarnavka, V Scukanec-Spoljar, M Allen, RH Stabler, S Uzelac, L Vugrek, O Wagner, C Zeisel, S Mudd, SH TI S-adenosylhomocysteine hydrolase deficiency in a human: A genetic disorder of methionine metabolism SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID GLYCINE N-METHYLTRANSFERASE; TOTAL HOMOCYSTEINE; DNA METHYLATION; PLASMA HOMOCYSTEINE; CREATINE DEFICIENCY; MASS-SPECTROMETRY; FOLATE-DEFICIENCY; COPPER-BINDING; INBORN ERROR; SERUM AB We report studies of a Croatian boy, a proven case of human S-adenosylhomocysteine (AdoHcy) hydrolase deficiency. Psychomotor development was slow until his fifth month; thereafter, virtually absent until treatment was started. He had marked hypotonia with elevated serum creatine kinase and transaminases, prolonged prothrombin time and low albumin. Electron microscopy of muscle showed numerous abnormal myelin figures; liver biopsy showed mild hepatitis with sparse rough endoplasmic reticulum. Brain MRI at 12.7 months revealed white matter atrophy and abnormally slow myelination. Hypermethioninemia was present in the initial metabolic study at age 8 months, and persisted (up to 784 muM) without tyrosine elevation. Plasma total homocysteine was very slightly elevated for an infant to 14.5-15.9 muM. In plasma, S-adenosylmethionine was 30-fold and AdoHcy 150-fold elevated. Activity of AdoHcy hydrolase was approximate to3% of control in liver and was 5-10% of the control values in red blood cells and cultured fibroblasts. We found no evidence of a soluble inhibitor of the enzyme in extracts of the patient's cultured fibroblasts. Additional pretreatment abnormalities in plasma included low concentrations of phosphatidylcholine and choline, with elevations of guanidinoacetate, betaine, dimethylglycine, and cystathionine. Leukocyte DNA was hypermethylated. Gene analysis revealed two mutations in exon 4: a maternally derived stop codon, and a paternally derived missense mutation. We discuss reasons for biochemical abnormalities and pathophysiological aspects of AdoHcy hydrolase deficiency. C1 Univ Zagreb, Hosp Ctr, Dept Pediat, Zagreb 10000, Croatia. Univ Zagreb, Hosp Ctr, Dept Neuropathol, Zagreb 10000, Croatia. Univ Zagreb, Hosp Ctr, Dept Radiol, Zagreb 10000, Croatia. Univ Zagreb, Hosp Ctr, Dept Pathol, Zagreb 10000, Croatia. Univ Zagreb, Hosp Ctr, Clin Inst Lab Diag, Zagreb 10000, Croatia. NIMH, Mol Biol Lab, Bethesda, MD 20892 USA. Univ N Carolina, Sch Publ Hlth, Dept Nutr, Chapel Hill, NC 27599 USA. Univ N Carolina, Sch Med, Chapel Hill, NC 27599 USA. Rudjer Boskovic Inst, Dept Mol Med, Zagreb 10000, Croatia. Univ Colorado, Hlth Sci Ctr, Div Hematol, Denver, CO 80262 USA. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Univ Zagreb, Childrens Hosp, Zagreb 10000, Croatia. Univ Arkansas Med Sci, Dept Pediat, Little Rock, AR 72202 USA. George Washington Univ, Washington, DC 20422 USA. Vet Affairs Med Ctr, Washington, DC 20422 USA. Univ Heidelberg, Childrens Hosp, D-69120 Heidelberg, Germany. Vanderbilt Univ, Dept Biochem, Nashville, TN 37232 USA. Dept Vet Affairs Med Ctr, Nashville, TN 37232 USA. RP Baric, I (reprint author), Univ Zagreb, Hosp Ctr, Dept Pediat, Kispaticeva 12, Zagreb 10000, Croatia. EM ibaric@kbc-zagreb.hr FU NIDDK NIH HHS [DK 15289, DK 55865, R37 DK015289, DK 54849, R01 DK015289, R01 DK055865] NR 52 TC 105 Z9 110 U1 0 U2 12 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 23 PY 2004 VL 101 IS 12 BP 4234 EP 4239 DI 10.1073/pnas.0400658101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 806ZQ UT WOS:000220472200045 PM 15024124 ER PT J AU Wendler, D Miller, FG AF Wendler, D Miller, FG TI Deception in the pursuit of science SO ARCHIVES OF INTERNAL MEDICINE LA English DT Editorial Material ID INFORMED CONSENT; PERCEPTIONS; PSYCHOLOGY; TRIAL C1 NIH, Dept Clin Bioeth, Bethesda, MD 20892 USA. RP Wendler, D (reprint author), NIH, Dept Clin Bioeth, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM dwendler@nih.gov NR 29 TC 45 Z9 46 U1 1 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAR 22 PY 2004 VL 164 IS 6 BP 597 EP 600 DI 10.1001/archinte.164.6.597 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 804QQ UT WOS:000220313600003 PM 15037487 ER PT J AU Shafrir, Y Guy, HR AF Shafrir, Y Guy, HR TI STAM: simple Transmembrane Alignment Method SO BIOINFORMATICS LA English DT Article ID MULTIPLE SEQUENCE ALIGNMENT; X-RAY-STRUCTURE; SECONDARY STRUCTURE; POTASSIUM CHANNEL; CRYSTAL-STRUCTURE; ANGSTROM RESOLUTION; GAP PENALTIES; PROTEIN; PREDICTION; RHODOPSIN AB Motivation: The database of transmembrane protein (TMP) structures is still very small. At the same time, more and more TMP sequences are being determined. Molecular modeling is an interim answer that may bridge the gap between the two databases. The first step in homology modeling is to achieve a good alignment between the target sequences and the template structure. However, since most algorithms to obtain the alignments were constructed with data derived from globular proteins, they perform poorly when applied to TMPs. In our application, we automate the alignment procedure and design it specifically for TMP. We first identify segments likely to form transmembrane alpha-helices. We then apply different sets of criteria for transmembrane and non-transmembrane segments. For example, the penalty for insertion/deletions in the transmembrane segments is much higher than that of a penalty in the loop region. Different substitution matrices are used since the frequencies of occurrence of the various amino acids differ for transmembrane segments and water-soluble domains. Results: This program leads to better models since it does not treat the protein as a single entity with the same properties, but accounts for the different physical properties of the various segments. STAM is the first multisequence alignment program that is directly targeted at transmembrane proteins. C1 NCI, LECB, Bethesda, MD 20892 USA. RP Shafrir, Y (reprint author), NCI, LECB, MSC 5677,12 South Dr, Bethesda, MD 20892 USA. EM yinon@nih.gov NR 34 TC 13 Z9 14 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD MAR 22 PY 2004 VL 20 IS 5 BP 758 EP U644 DI 10.1093/bioinformatics/btg482 PG 38 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 807ER UT WOS:000220485300021 PM 14751993 ER PT J AU Wykoff, CC Sotiriou, C Cockman, ME Ratcliffe, PJ Maxwell, P Liu, E Harris, AL AF Wykoff, CC Sotiriou, C Cockman, ME Ratcliffe, PJ Maxwell, P Liu, E Harris, AL TI Gene array of VHL mutation and hypoxia shows novel hypoxia-induced genes and that cyclin D1 is a VHL target gene SO BRITISH JOURNAL OF CANCER LA English DT Article DE VHL; hypoxia; cyclin D1; hypoxia inducible factor 1; renal ID TUMOR-SUPPRESSOR PROTEIN; RENAL-CELL CARCINOMA; LINDAU-DISEASE; EXPRESSION; IDENTIFICATION; PHENOTYPE; LINE AB Gene expression analysis was performed on a human renal cancer cell line (786-0) with mutated VHL gene and a transfectant with wild-type VHL to analyse genes regulated by VHL and to compare with the gene programme regulated by hypoxia. There was a highly significant concordance of the global gene response to hypoxia and genes suppressed by VHL. Cyclin D1 was the most highly inducible transcript and 14-3-3 epsilon was downregulated. There were some genes regulated by VHL but not hypoxia in the renal cell line, suggesting a VHL role independent of hypoxia. However in nonrenal cell lines they were hypoxia regulated. These included several new pathways regulated by hypoxia, including RNase 6PL, collagen type I alpha 1, integrin alpha 5, ferritin light polypeptide, JM4 protein, transgelin and L1 cell adhesion molecule. These were not found in a recent SAGE analysis of the same cell line. Hypoxia induced downregulation of Cyclin D1 in nonrenal cells via an HIF independent pathway. The selective regulation of Cyclin D I by hypoxia in renal cells may therefore contribute to the tissue selectivity of VHL mutation. C1 John Radcliffe Hosp, Weatherall Inst Mol Med, Oncol Mol Lab, Canc Res UK, Oxford OX3 9DS, England. NCI, Div Clin Sci, Bethesda, MD 20892 USA. Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England. RP Harris, AL (reprint author), John Radcliffe Hosp, Weatherall Inst Mol Med, Oncol Mol Lab, Canc Res UK, Oxford OX3 9DS, England. EM aharris.lab@cancer.org.uk RI Liu, Edison/C-4141-2008; Maxwell, Patrick/C-5557-2008; OI Maxwell, Patrick/0000-0002-0338-2679; Ratcliffe, Peter/0000-0002-2853-806X; Harris, Adrian/0000-0003-1376-8409 NR 27 TC 76 Z9 80 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD MAR 22 PY 2004 VL 90 IS 6 BP 1235 EP 1243 DI 10.1038/sj.bjc.6601657 PG 9 WC Oncology SC Oncology GA 812NT UT WOS:000220846900022 PM 15026807 ER PT J AU van Gijssel, HE Schild, LJ Watt, DL Roth, MJ Wang, GQ Dawsey, SM Albert, PS Qiao, YL Taylor, PR Dong, ZW Poirier, MC AF van Gijssel, HE Schild, LJ Watt, DL Roth, MJ Wang, GQ Dawsey, SM Albert, PS Qiao, YL Taylor, PR Dong, ZW Poirier, MC TI Polycyclic aromatic hydrocarbon-DNA adducts determined by semiquantitative immunohistochemistry in human esophageal biopsies taken in 1985 SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE immunohistochemistry; automated cellular imaging system; Linxian; China; superficial squamous epithelium; basal epithelium ID CANCER RISK; CHINA; LINXIAN; CARCINOGENS; CELLS AB Esophageal endoscopic biopsy samples were obtained in 1985 in Linxian, China, a region with very high esophageal cancer incidence rates, and where ingested food is known to contain substantial amounts of polycyclic aromatic hydrocarbons (PAHs). In this study, the automated cellular imaging system (ACIS) was used for localization and semi-quantitation of PAH-DNA adducts. Fresh tissue sections were cut from archived paraffin blocks and incubated with an antiserum elicited against DNA modified with 7beta,8alpha-dihydroxy-9alpha,10alpha-epoxy-7,8,9,10-tetrahydro-benzo[a]pyrene (BPDE). Nuclear PAH-DNA adduct staining was observed in four out of five human samples incubated with the anti-BPDE-DNA. By visual inspection, nuclei in the basal layer of the esophageal epithelium had higher levels of PAH-DNA adducts compared to those found in the adjacent superficial squamous layer. Nuclear PAH-DNA staining was absent in serial sections incubated with either normal rabbit serum or BPDE-DNA-antiserum previously absorbed with the immunogen BPDE-DNA. Semi-quantitative evaluation by ACIS revealed that per nucleus values for PAH-DNA adducts in the basal layer of the esophageal epithelium were 5- to 40-fold higher than those in the adjacent superficial squamous layer (P < 0.0001, using a random effects model). This pilot study demonstrates the presence of PAH-DNA adducts in archived paraffin-embedded endoscopic esophageal biopsy samples that are close to 20 years old, and suggests that an appropriate set of archived samples could be used to prospectively correlate PAH-DNA adduct formation with risk of esophageal cancer development. (C) 2004 Elsevier B.V. All rights reserved. C1 NIH, Cellular Carcinogenesis & Tumor Promot Lab, Ctr Canc Res, Bethesda, MD 20892 USA. NIH, Canc Prevent Studies Branch, Ctr Canc Res, Bethesda, MD 20892 USA. Chinese Acad Med Sci, Inst Canc, Beijing 100021, Peoples R China. NCI, Biometr Res Branch, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. Valley City State Univ, Valley City, ND 58072 USA. Univ Connecticut, Dept Chem, Storrs, CT 06269 USA. RP Poirier, MC (reprint author), NIH, Cellular Carcinogenesis & Tumor Promot Lab, Ctr Canc Res, Bldg 37,Room 4032,37 Convent Dr,MSC-4255, Bethesda, MD 20892 USA. EM poirierm@exchange.nih.gov RI Qiao, You-Lin/B-4139-2012 OI Qiao, You-Lin/0000-0001-6380-0871 NR 20 TC 25 Z9 26 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD MAR 22 PY 2004 VL 547 IS 1-2 BP 55 EP 62 DI 10.1016/j.mrfmmm.2003.11.010 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 806FD UT WOS:000220418900007 PM 15013699 ER PT J AU Wang, Y Haughey, NJ Mattson, MP Furukawa, K AF Wang, Y Haughey, NJ Mattson, MP Furukawa, K TI Dual effects of ATP on rat hippocampal synaptic plasticity SO NEUROREPORT LA English DT Article DE ATP; calcium; hippocampus; P2X receptors; P2Y receptors; synaptic plasticity ID LONG-TERM POTENTIATION; LOW-FREQUENCY STIMULATION; GTP-BINDING PROTEINS; P2X RECEPTORS; N-ETHYLMALEIMIDE; MOLECULAR PHYSIOLOGY; CA1 NEURONS; RELEASE; ADENOSINE; SLICES AB Although ATP is reported to modulate synaptic plasticity, the mechanism of action of ATP on synaptic transmission is not fully understood. Here we show that ATP enhances long-term potentiation (LTP), and P2X receptor antagonists inhibit this ATP effect, but do not affect paired pulse facilitation (PPF) in rat hippocampal slices. ATP rapidly increases intracellular calcium, and P2X receptor antagonists inhibit this increase in cultured dissociated neurons. These results indicate that ATP enhances LTP via activation of postsynaptic P2X receptors. A pertussis toxin-sensitive G-protein inhibitor significantly attenuates PPF, although it does not affect LTP, indicating that presynaptic P2Y receptors also play an important role in neuronal plasticity. We conclude that ATP modulates synaptic plasticity via dual effects on pre- and post-synaptic mechanisms. C1 NIA, Synapt Physiol Unit, Baltimore, MD 21224 USA. NIA, Cellular & Mol Neurosci Sect, Neurosci Lab, Gerontol Res Ctr, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21287 USA. RP Furukawa, K (reprint author), NIA, Synapt Physiol Unit, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM furukawaka@grc.nia.nih.gov RI Mattson, Mark/F-6038-2012 NR 20 TC 27 Z9 27 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD MAR 22 PY 2004 VL 15 IS 4 BP 633 EP 636 DI 10.1097/01.wnr.0000116970.73984.6a PG 4 WC Neurosciences SC Neurosciences & Neurology GA 871NJ UT WOS:000225140100012 PM 15094466 ER PT J AU Oishi, S Kang, SU Liu, HP Zhang, MC Yang, DJ Deschamps, JR Burke, TR AF Oishi, S Kang, SU Liu, HP Zhang, MC Yang, DJ Deschamps, JR Burke, TR TI Synthesis of alpha,alpha-disubstituted 4-phosphonophenylalanine analogues as conformationally-constrained phosphotyrosyl mimetics SO TETRAHEDRON LA English DT Article DE enantioselective; phosphotyrosyl mimetic; conformational constraint ID SH2 DOMAIN BINDING; PHOSPHATE-CONTAINING LIGANDS; ALPHA-AMINO-ACIDS; O-PHOSPHOTYROSINE; PEPTIDE-SYNTHESIS; DESIGN; INHIBITORS; PEPTIDOMIMETICS; KINASES AB Syntheses of N-Boc (S)-4-(diethylphosphono)-(alpha-methyl)phenylalanine [Boc-(alpha-Me)Phe(4-PO3Et2)-OH] (9) and N-Boc (S)-2amino-6-(diethylphosphono)tetralin-2-carboxylic acid [Boc-Atc(6-PO3Et2)-OH] (18) are reported as conformationally-constrained phosphotyrosyl mimetics suitably protected for peptide synthesis. Both syntheses proceeded through chiral arylhalides that are converted to arylphosphonates by palladium-catalyzed cross coupling with diethylphosphite. These amino acid analogues may be useful in the study of cellular signal transduction processes. (C) 2004 Elsevier Ltd. All rights reserved. C1 NCI, Med Chem Lab, Ctr Canc Res, NIH, Frederick, MD 21702 USA. Univ Michigan, Sch Med, Dept Hematol Oncol, Ann Arbor, MI 48109 USA. USN, Res Lab, Struct Matter Lab, Washington, DC 20375 USA. RP Burke, TR (reprint author), NCI, Med Chem Lab, Ctr Canc Res, NIH, POB B,Bldg 376 Boyles St, Frederick, MD 21702 USA. EM tburke@helix.nih.gov RI Burke, Terrence/N-2601-2014; Oishi, Shinya/C-1350-2011; OI Oishi, Shinya/0000-0002-2833-2539; Deschamps, Jeffrey/0000-0001-5845-0010 NR 29 TC 20 Z9 21 U1 1 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0040-4020 J9 TETRAHEDRON JI Tetrahedron PD MAR 22 PY 2004 VL 60 IS 13 BP 2971 EP 2977 DI 10.1016/j.tet.2004.02.005 PG 7 WC Chemistry, Organic SC Chemistry GA 805UF UT WOS:000220390500007 ER PT J AU Popescu, NC Durkin, ME AF Popescu, NC Durkin, ME TI Rho GTPase activating protein cDNA on chromosome 13q12 is the deleted in liver cancer (DLC2) gene SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Editorial Material C1 NCI, Ctr Canc Res, Expt Carcinogenesis Lab, Bethesda, MD 20892 USA. RP Popescu, NC (reprint author), NCI, Ctr Canc Res, Expt Carcinogenesis Lab, Convent Dr MSC 4262,Bldg 37,Room 4128, Bethesda, MD 20892 USA. EM popescun@mail.nih.gov NR 2 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 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAR 19 PY 2004 VL 315 IS 4 BP 781 EP 781 DI 10.1016/j.bbrc.2004.02.010 PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 801OQ UT WOS:000220105600001 PM 14985079 ER PT J AU Yoshioka, Y Tsutsumi, Y Ikemizu, S Yamamoto, Y Shibata, H Nishibata, T Mukai, Y Okamoto, T Taniai, M Kawamura, M Abe, Y Nakagawa, S Nagata, S Yamagata, Y Mayumi, T AF Yoshioka, Y Tsutsumi, Y Ikemizu, S Yamamoto, Y Shibata, H Nishibata, T Mukai, Y Okamoto, T Taniai, M Kawamura, M Abe, Y Nakagawa, S Nagata, S Yamagata, Y Mayumi, T TI Optimal site-specific PEGylation of mutant TNF-alpha improves its antitumor potency SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID TUMOR-NECROSIS-FACTOR; PHASE-I; POLYETHYLENE-GLYCOL; ADVANCED CANCER; SOLID TUMORS; COPOLYMER; TOXICITY; MICE AB Recently, we created a lysine-deficient mutant tumor necrosis factor-alpha [mTNF-alpha-Lys(-)] with full bioactivity in vitro compared with wild-type TNF-alpha (wTNF-alpha), and site-specific PEGylation of mTNF-alpha-Lys(-) was found to selectively enhance its in vivo antitumor activity. In this study, we attempted to optimize this PEGylation of mTNF-alpha-Lys(-) to further improve its therapeutic potency. mTNF-alpha-Lys(-) was site-specifically modified at its N-terminus with linear polyethylene glycol (LPEG) or branched PEG (BPEG). While randomly mono-PEGylated wTNF-alpha(ran-LPEG(5K)-wTNF-alpha) with 5 kDa of LPEG (LPEG(5K)) had about only 4% in vitro bioactivity of wTNF-a, mono-PEGylated mTNF-alpha-Lys(-) [sp-PEG-mTNF-alpha-Lys(-)] with LPEG(5K), LPEG(20K), BPEG(10K), and BPEG(40K) had 82%, 58%, 93%, and 65% bioactivities of mTNF-alpha-Lys(-), respectively. sp-LPEG-mTNF-alpha-Lys(-) and sp-BPEGIOKmTNF-alpha-Lys(-) had much superior antitumor activity to those of both unmodified TNF-alphas and ran-LPEG(5K)-wTNF-alpha, though sp-BPEG(40K)-mTNF-alpha-Lys(-) did not show in vivo antitumor activity. Thus, the molecular shape and weight of PEG may strongly influence the in vivo antitumor activity of sp-PEG-mTNF-a-Lys(-). alpha 2004 Elsevier Inc. All rights reserved. C1 Osaka Univ, Grad Sch Pharmaceut Sci, Dept Biopharmaceut, Suita, Osaka 5650871, Japan. Kumamoto Univ, Grad Sch Pharmaceut Sci, Dept Biol Struct, Kumamoto 8620973, Japan. NCI, Mol Biol Lab, Ira Pastans Lab, Div Basic Sci,NIH, Bethesda, MD 20892 USA. RP Tsutsumi, Y (reprint author), Osaka Univ, Grad Sch Pharmaceut Sci, Dept Biopharmaceut, 1-6 Yamadaoka, Suita, Osaka 5650871, Japan. EM tsutsumi@phs.osaka-u.ac.jp RI Abe, Yasuhiro/F-5206-2016 OI Abe, Yasuhiro/0000-0002-5931-6590 NR 26 TC 44 Z9 47 U1 1 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAR 19 PY 2004 VL 315 IS 4 BP 808 EP 814 DI 10.1016/j.bbrc.2004.01.125 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 801OQ UT WOS:000220105600006 PM 14985084 ER PT J AU Kurebayashi, S Nakajima, T Kim, SC Chang, CY McDonnell, DP Renaud, JP Jetten, AM AF Kurebayashi, S Nakajima, T Kim, SC Chang, CY McDonnell, DP Renaud, JP Jetten, AM TI Selective LXXLL peptides antagonize transcriptional activation by the retinoid-related orphan receptor ROR gamma SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE retinoid; lymphoma; receptor; ROR; co-activator ID LIGAND-BINDING DOMAIN; X-RAY-STRUCTURE; NUCLEAR RECEPTORS; COACTIVATOR; PROTEIN; BETA; REPRESSION; CHROMATIN; COMPLEXES; ALPHA AB The retinoid-related orphan receptor gamma (RORgamma) has been shown to function as a positive regulator of transcription in many cell lines. Transcriptional activation by nuclear receptors involves recruitment of co-activators that interact with receptors through their LXXLL motifs (NR box). In this study, we analyze the interaction of RORgamma with the co-activator SRC1 and use a series of LXXLL-containing peptides to probe for changes in the conformation of the co-activator interaction surface of the RORgamma LBD. We demonstrate that the H3-4/H12 co-activator interaction surface of RORgamma displays a selectivity for LXXLL peptides that is distinct from those of other nuclear receptors. LXXLL peptides that interacted with RORgamma efficiently antagonized RORgamma-mediated transcriptional activation. Mutations E(502)Q and (YF)-F-500 in H12, and K(334)A, Q(347)A, and (ID)-D-348 in H3 and H4 of RORgamma, severely impact the recruitment of LXXLL peptides. The effects of these mutations are consistent with predictions made on the basis of the structure of the RORgamma(LBD) derived through homology modeling. These peptide antagonists provide a useful tool to analyze the conformation changes in the RORgamma(LBD) and to study RORgamma receptor signaling. Published by Elsevier Inc. C1 Natl Inst Environm Sci, Cell Biol Sect, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA. Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA. Inst Genet & Biol Mol & Cellulaire, Dept Struct Biol & Struct Genom, F-67404 Illkirch Graffenstaden, France. RP Jetten, AM (reprint author), Natl Inst Environm Sci, Cell Biol Sect, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA. EM jetten@niehs.nih.gov OI Renaud, Jean-Paul/0000-0001-9180-5426; Jetten, Anton/0000-0003-0954-4445 NR 27 TC 28 Z9 29 U1 0 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAR 19 PY 2004 VL 315 IS 4 BP 919 EP 927 DI 10.1016/j.bbrc.2004.01.131 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 801OQ UT WOS:000220105600022 PM 14985100 ER PT J AU Leong, GM Subramaniam, N Issa, LL Barry, JB Kino, T Driggers, PH Hayman, MJ Eisman, JA Gardiner, EM AF Leong, GM Subramaniam, N Issa, LL Barry, JB Kino, T Driggers, PH Hayman, MJ Eisman, JA Gardiner, EM TI Ski-interacting protein, a bifunctional nuclear receptor coregulator that interacts with N-CoR/SMRT and p300 SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE SKIP; NcoA-62; N-CoR/SMRT; p300; nuclear receptor; transcription; vitamin D; retinoid X receptor ID VITAMIN-D-RECEPTOR; RETINOID-X-RECEPTOR; MEDIATED TRANSCRIPTION; GENE-EXPRESSION; COACTIVATOR; REPRESSION; FAMILY; CELLS; DIFFERENTIATION; COREPRESSORS AB Ski-interacting protein (SKIP), a vitamin D receptor (VDR) coactivator, also functions as a repressor in Notch signalling in association with the corepressor SMRT. Here we show that SKIP bifunctionally modulates (activates or represses) Retinoid-X receptor (RXR)- and VDR-dependent gene transcription in a cell line-specific manner, with activation in CV-I and repression in P19 cells. The coactivator function of SKIP in these cells appeared to correlate with the relative level and ratio of expression of N-CoR and p300, with greater SKIP activation in higher p300-expressing and lower N-CoR-expressing cell-lines. C-terminal deletion of SKIP (del334-536aa) was associated with strong activation in both CV-1 and P19 cells. The corepressors N-CoR and SMRT and the coregulator p300 interacted with SKIP through the same N-terminal region (1-200aa). Overall these results suggest that transcriptional action of SKIP may depend on distinct functional domains and cell line-specific interactions with both corepressors and coactivators. (C) 2004 Elsevier Inc. All rights reserved. C1 Garvan Inst Med Res, Bone & Mineral Res Program, Sydney, NSW, Australia. NICHHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynaecol, Bethesda, MD 20814 USA. SUNY Stony Brook, Dept Mol Genet & Microbiol, Stony Brook, NY 11794 USA. RP Leong, GM (reprint author), Garvan Inst Med Res, Bone & Mineral Res Program, Sydney, NSW, Australia. EM g.leong@garvan.org.au RI Eisman, John/C-2886-2014 FU NCI NIH HHS [CA28146, CA42573] NR 36 TC 36 Z9 41 U1 1 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAR 19 PY 2004 VL 315 IS 4 BP 1070 EP 1076 DI 10.1016/j.bbrc.2004.02.004 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 801OQ UT WOS:000220105600044 PM 14985122 ER PT J AU Wu, LJC Leenders, AGM Cooperman, S Meyron-Holtz, E Smith, S Land, W Tsai, RYL Berger, UV Sheng, ZH Rouault, TA AF Wu, LJC Leenders, AGM Cooperman, S Meyron-Holtz, E Smith, S Land, W Tsai, RYL Berger, UV Sheng, ZH Rouault, TA TI Expression of the iron transporter ferroportin in synaptic vesicles and the blood-brain barrier SO BRAIN RESEARCH LA English DT Article DE iron transport; synaptic vesicles; endothelial transport; neurodegeneration ID RAT-BRAIN; METABOLISM; ACCUMULATION; DEFICIENCY; CLONING; DISEASE; SYSTEM AB Iron homeostasis in the mammalian brain is an important and poorly understood subject. Transferrin-bound iron enters the endothelial cells of the blood-brain barrier from the systemic circulation, and iron subsequently dissociates from transferrin to enter brain parenchyma by an unknown mechanism. In recent years, several iron transporters, including the iron importer DMT1 (Ireg1, NITP, DCT1) and the iron exporter ferroportin (SLC11A3, Ireg, MTP1) have been cloned and characterized. To better understand brain iron homeostasis, we have characterized the distribution of ferroportin, the presumed intestinal iron exporter, and have evaluated its potential role in regulation of iron homeostasis in the central nervous system. We discovered using in situ hybridization and immunohistochemistry that ferroportin is expressed in the endothelial cells of the blood-brain barrier, in neurons, oligodendrocytes, astrocytes, and the choroid plexus and ependymal cells. In addition, we discovered using techniques of immunoelectron microscopy and biochemical purification of synaptic vesicles that ferroportin is associated with synaptic vesicles. In the blood-brain barrier, it is likely that ferroportin serves as a molecular transporter of iron on the abluminal membrane of polarized endothelial cells. The role of ferroportin in synaptic vesicles is unknown, but its presence at that site may prove to be of great importance in neuronal iron toxicity. The widespread representation of ferroportin at sites such as the blood-brain barrier and synaptic vesicles raises the possibility that trafficking of elemental iron may be instrumental in the distribution of iron in the central nervous system. Published by Elsevier B.V. C1 NICHHD, Cell Biol & Metab Branch, NICHD, Bethesda, MD 20892 USA. NINCDS, Synapt Funct Unit, Bethesda, MD 20892 USA. NINCDS, Synapt Funct Unit, Bethesda, MD 20892 USA. UB In Situ, Natick, MA USA. RP Rouault, TA (reprint author), NICHHD, Cell Biol & Metab Branch, NICHD, Bldg 18T,Room 101, Bethesda, MD 20892 USA. EM trou@helix.nih.gov RI Meyron-Holtz, Esther/B-5991-2013 NR 30 TC 116 Z9 125 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD MAR 19 PY 2004 VL 1001 IS 1-2 BP 108 EP 117 DI 10.1016/j.brainres.2003.10.066 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 812AM UT WOS:000220812400011 PM 14972659 ER PT J AU Xu, Q Wang, YS Dabdoub, A Smallwood, PM Williams, J Woods, C Kelley, MW Jiang, L Tasman, W Zhang, K Nathans, J AF Xu, Q Wang, YS Dabdoub, A Smallwood, PM Williams, J Woods, C Kelley, MW Jiang, L Tasman, W Zhang, K Nathans, J TI Vascular development in the retina and inner ear: Control by Norrin and Frizzled-4, a high-affinity ligand-receptor pair SO CELL LA English DT Article ID FAMILIAL EXUDATIVE VITREORETINOPATHY; SIGNALING PATHWAY; DISEASE; PROTEIN; ANGIOGENESIS; MOUSE; GENE; LOCALIZATION; DROSOPHILA; BINDING AB Incomplete retinal vascularization occurs in both Norrie disease and familial exudative vitreoretinopathy (FEVR). Norrin, the protein product of the Norrie disease gene, is a secreted protein of unknown biochemical function. One form of FEVR is caused by defects in Frizzled-4 (Fz4), a presumptive Writ receptor. We show here that Norrin and Fz4 function as a ligand-receptor pair based on (1) the similarity in vascular phenotypes caused by Norrin and Fz4 mutations in humans and mice, (2) the specificity and high affinity of Norrin-Fz4 binding, (3) the high efficiency with which Norrin induces Fz4- and Lrp-dependent activation of the classical Wnt pathway, and (4) the signaling defects displayed by disease-associated variants of Norrin and Fz4. These data define a Norrin-Fz4 signaling system that plays a central role in vascular development in the eye and ear, and they indicate that ligands unrelated to Writs can act through Fz receptors. C1 Johns Hopkins Univ, Sch Med, Howard Hughes Med Inst, Dept Mol Biol & Genet, Baltimore, MD 21218 USA. Johns Hopkins Univ, Sch Med, Howard Hughes Med Inst, Dept Neurosci, Baltimore, MD 21218 USA. Johns Hopkins Univ, Sch Med, Howard Hughes Med Inst, Dept Ophthalmol, Baltimore, MD 21218 USA. NIDCD, Sect Dev Neurosci, NIH, Rockville, MD 20850 USA. Univ Utah, Program Human Mol Biol & Gneet, Dept Ophthalmol & Visual Sci, Salt Lake City, UT 84112 USA. Wills Eye Hosp & Res Inst, Dept Ophthalmol, Philadelphia, PA 19107 USA. RP Nathans, J (reprint author), Johns Hopkins Univ, Sch Med, Howard Hughes Med Inst, Dept Mol Biol & Genet, Baltimore, MD 21218 USA. EM jnathans@jhmi.edu RI Jiang, Li/C-9537-2012 NR 39 TC 413 Z9 431 U1 4 U2 29 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD MAR 19 PY 2004 VL 116 IS 6 BP 883 EP 895 DI 10.1016/S0092-8674(04)00216-8 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 821YS UT WOS:000221499900013 PM 15035989 ER PT J AU Cui, WW Tomarev, SI Piatigorsky, J Chepelinsky, AB Duncan, MK AF Cui, WW Tomarev, SI Piatigorsky, J Chepelinsky, AB Duncan, MK TI Mafs, Prox1, and Pax6 can regulate chicken beta B1-crystallin gene expression SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID A-CRYSTALLIN GENE; LENS DEVELOPMENT; C-MAF; TRANSCRIPTION FACTORS; HOMEOBOX GENE; TRANSGENIC MICE; MOUSE LENS; MOLECULAR-FEATURES; RESPONSIVE ELEMENT; DELTA-CRYSTALLIN AB During lens fiber cell differentiation, the regulation of crystallin gene expression is coupled with dramatic morphological changes. Here we report that Mafs, Prox1, and Pax6, which are essential transcription factors for normal lens development, bind to three functionally important cis elements, PL1, PL2, and OL2, in the chicken betaB1-crystallin promoter and may cooperatively direct the transcription of this lens fiber cell preferred gene. Gel shift assays demonstrated that Mafs bind to the MARE-like sequences in the PL1 and PL2 elements, whereas Prox1, a sequence-specific DNA-binding protein like its Drosophila homolog Prospero, interacts with the OL2 element. Furthermore, Pax6, a known repressor of the chicken betaB1-crystallin promoter, binds to all three of these cis elements. In transfection assays, Mafs and Prox1 activated the chicken betaB1-crystallin promoter; however, their transactivation ability was repressed when co-transfected with Pax6. Taken together with the known spatiotemporal expression patterns of Mafs, Prox1, and Pax6 in the developing lens, we propose that Pax6 occupies and represses the chicken betaB1-crystallin promoter in lens epithelial cells, and is displaced by Prox1 and Mafs, which activate the promoter, in differentiating cortical fiber cells. C1 Univ Delaware, Dept Biol Sci, Newark, DE 19716 USA. NEI, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RP Duncan, MK (reprint author), Univ Delaware, Dept Biol Sci, Newark, DE 19716 USA. EM duncanm@udel.edu OI Duncan, Melinda/0000-0003-1570-322X FU NEI NIH HHS [EY12221] NR 60 TC 59 Z9 60 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 19 PY 2004 VL 279 IS 12 BP 11088 EP 11095 DI 10.1074/jbc.M312414200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 802IQ UT WOS:000220157600032 PM 14707122 ER PT J AU Deterding, LJ Ramirez, DC Dubin, JR Mason, RP Tomer, KB AF Deterding, LJ Ramirez, DC Dubin, JR Mason, RP Tomer, KB TI Identification of free radicals on hemoglobin from its self-peroxidation using mass spectrometry and immuno-spin trapping - Observation of a histidinyl radical SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HYDROGEN-PEROXIDE; CYTOCHROME-C; CROSS-LINKING; MYOGLOBIN; SITE; METMYOGLOBIN; SUPEROXIDE; OXIDANTS; PEPTIDES; DISEASE AB In an effort to understand the mechanism of radical formation on heme proteins, the formation of radicals on hemoglobin was initiated by reaction with hydrogen peroxide in the presence of the spin trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO). The DMPO nitrone adducts were analyzed by mass spectrometry (MS) and immuno-spin trapping. The spin-trapped protein adducts were then subjected to tryptic digestion and MS analyses. When hemoglobin was reacted with hydrogen peroxide (H2O2) in the presence of DMPO, a DMPO nitrone adduct could be detected by immuno-spin trapping. To verify that DMPO adducts of the protein free radicals had been formed, the reaction mixtures were analyzed by flow injection electrospray ionization mass spectrometry (ESI/MS). The ESI mass spectrum of the hemoglobin/H2O2/DMPO sample shows one adduct each on both the alpha chain and the beta chain of hemoglobin which corresponds in mass to the addition of one DMPO molecule. The nature of the radicals formed on hemoglobin was explored using proteolysis techniques followed by liquid chromatography/mass spectrometry (LC/MS) and tandem mass spectrometry (MS/MS) analyses. The following sites of DMPO addition were identified on hemoglobin: Cys-93 of the beta chain, and Tyr-42, Tyr-24, and His-20 of the alpha chain. Because of the pi-pi interaction of Tyr-24 and His-20, the unpaired electron is apparently delocalized on both the tyrosine and histidine residue (pi-pi stacked pair radical). C1 NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. RP Deterding, LJ (reprint author), NIEHS, Struct Biol Lab, NIH, POB 12233,MD F0-03, Res Triangle Pk, NC 27709 USA. EM deterdi2@niehs.nih.gov RI Tomer, Kenneth/E-8018-2013; RAMIREZ, DARIO/K-3312-2013 OI RAMIREZ, DARIO/0000-0001-6725-3326 NR 37 TC 77 Z9 79 U1 1 U2 9 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 19 PY 2004 VL 279 IS 12 BP 11600 EP 11607 DI 10.1074/jbc.M310704200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 802IQ UT WOS:000220157600093 PM 14699100 ER PT J AU Rishi, V Gal, J Krylov, D Fridriksson, J Boysen, MS Mandrup, S Vinson, C AF Rishi, V Gal, J Krylov, D Fridriksson, J Boysen, MS Mandrup, S Vinson, C TI SREBP-1 dimerization specificity maps to both the helix-loop-helix and leucine zipper domains - Use of a dominant negative SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID COILED-COIL SYSTEM; DNA-BINDING; GENE-EXPRESSION; AMINO-ACID; TRANSCRIPTION FACTOR; B/HLH/Z DOMAIN; PROTEINS; CHOLESTEROL; STABILITY; RECOGNITION AB The mammalian SREBP family contains two genes that code for B-HLH-ZIP proteins that bind sequence-specific DNA to regulate the expression of genes involved in lipid metabolism. We have designed a dominant negative (DN), termed A-SREBP-1, that inhibits the DNA binding of either SREBP protein. A-SREBP-1 consists of the dimerization domain of B-SREBP-1 and a polyglutamic acid sequence that replaces the basic region. A-SREBP-1 heterodimerizes with either B-SREBP-1 or B-SREBP-2, and both heterodimers are more stable than B-SREBP-1 bound to DNA. Circular dichroism thermal denaturation studies show that the B-SREBP-1 . A-SREBP-1 heterodimer is - 9.8 kcal mol(-1) dimer(-1) more stable than the B-SREBP-1 homodimer. EMSA assays demonstrate that A-SREBP-1 can inhibit the DNA binding of either B-SREBP-1 or B-SREBP-2 in an equimolar competition but does not inhibit the DNA binding of the three B-HLH-ZIP proteins MAX, USF, or MITF, even at 100 molar eq. Chimeric proteins containing the HLH domain of SREBP-1 and the leucine zipper from either MAX, USF, or MITF indicate that both the HLH and leucine zipper regions of SREBP-1 contribute to its dimerization specificity. Transient co-transfection studies demonstrate that A-SREBP-1 can inhibit the transactivation of SREBP-1 and SREBP-2 but not USF. A-SREBP-1 may be useful in metabolic diseases where SREBP family members are overexpressed. C1 NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. Gene Log Inc, Gaithersburg, MD 20878 USA. Univ So Denmark, Odense Univ, Dept Biochem & Mol Biol, DK-5230 Odense, Denmark. RP Vinson, C (reprint author), NCI, Lab Metab, NIH, Bldg 37,Rm 3128C, Bethesda, MD 20892 USA. EM Vinsonc@dc37a.nci.nih.gov RI Mandrup, Susanne/B-6693-2008; OI Mandrup, Susanne/0000-0002-0961-5787 NR 35 TC 21 Z9 21 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 19 PY 2004 VL 279 IS 12 BP 11863 EP 11874 DI 10.1074/jbc.M308000200 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 802IQ UT WOS:000220157600123 PM 14702347 ER PT J AU Garman, SC Garboczi, DN AF Garman, SC Garboczi, DN TI The molecular defect leading to Fabry disease: Structure of human alpha-galactosidase SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE alpha-GAL; lysosomal storage disease; Fabry disease; EC 3.2.1.22; alpha-NAGAL ID FULL-LENGTH CDNA; N-ACETYLGALACTOSAMINIDASE; HUMAN-LIVER; GLYCOSIDASE MECHANISMS; CATALYTIC NUCLEOPHILE; REPLACEMENT THERAPY; BACULOVIRUS VECTOR; A-GENE; SEQUENCE; EXPRESSION AB Fabry disease is an X-linked lysosomal storage disease afflicting I in 40,000 males with chronic pain, vascular degeneration, cardiac impairment, and other symptoms. Deficiency in the lysosomal enzyme a-galactosidase (a-GAL) causes an accumulation of its substrate, which ultimately leads to Fabry disease symptoms. Here, we present the structure of the human a-GAL glycoprotein determined by X-ray crystallography. The structure is a homodimer with each monomer containing a (beta/alpha)(8) domain with the active site and an antiparallel beta domain. N-linked carbohydrate appears at six sites in the glycoprotein dimer, revealing the basis for lysosomal transport via the mannose-6-phosphate receptor. To understand how the enzyme cleaves galactose from glycoproteins and glycolipids, we also determined the structure of the complex of a-GAL with its catalytic product. The catalytic mechanism of the enzyme is revealed by the location of two aspartic acid residues (D170 and D231), which act as a nucleophile and an acid/base, respectively. As a point mutation in a-GAL can lead to Fabry disease, we have catalogued and plotted the locations of 245 missense and nonsense mutations in the three-dimensional structure. The structure of human a-GAL brings Fabry disease into the realm of molecular diseases, where insights into the structural basis of the disease phenotypes might help guide the clinical treatment of patients. Published by Elsevier Ltd. C1 NIAID, Struct Biol Sect, Immunogenet Lab, NIH, Rockville, MD 20852 USA. RP Garman, SC (reprint author), NIAID, Struct Biol Sect, Immunogenet Lab, NIH, Twinbrook II,12441 Parklawn Dr, Rockville, MD 20852 USA. EM sgarman@niaid.nih.gov NR 65 TC 171 Z9 186 U1 1 U2 12 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD MAR 19 PY 2004 VL 337 IS 2 BP 319 EP 335 DI 10.1016/j.jmb.2004.01.035 PG 17 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 803MW UT WOS:000220236200008 PM 15003450 ER PT J AU Mohanty, S Zubkov, S Gronenborn, AM AF Mohanty, S Zubkov, S Gronenborn, AM TI The solution NMR structure of Antheraea polyphemus PBP provides new insight into pheromone recognition by pheromone-binding proteins SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE Antheraca polyphemus; PBP; pheromone-binding protein; olfaction; NMR structure ID AUTOMATED NOE ASSIGNMENT; TORSION ANGLE DYNAMICS; MACROMOLECULAR STRUCTURES; SECONDARY STRUCTURE; MAMESTRA-BRASSICAE; SEXUAL ATTRACTION; CHEMICAL-SHIFT; LIGAND-BINDING; SILKWORM MOTH; SPECIFICITY AB Pheromone-binding proteins (PBPs) located in the antennae of male moth species play an important role in olfaction. They are carrier proteins, believed to transport volatile hydrophobic pheromone molecules across the aqueous sensillar lymph to the membrane-bound G protein-coupled olfactory receptor proteins. The roles of PBPs in molecular recognition 2 and the mechanisms of pheromone binding and release are poorly understood. Here, we report the NMR structure of a PBP frorn the giant silk of moth Antheraea polyphemus. This is the first structure of a PBP with specific acetate-binding function in vivo. The protein consists of nine a-helices: ala (residues 2-5), alphalb (8-12), alphalc (16-23), alpha2 (27-34), alpha3a (46-52), alpha3b (54-59), alpha4 (70-79), alpha5 (84-100) and alpha6 (107-125), held together by three disulfide bridges: 19-54, 50-108 and 97-117. A large hydrophobic cavity is located inside the protein, lined with side-chains from all nine helices. The acetate-binding site is located at the narrow end of the cavity formed by the helices alpha3b and alpha4. The pheromone can enter this cavity through an opening between the helix ala, the C-terminal end of the helix alpha6, and the loop between alpha2 and alpha3a. We suggest that Trp37 may play an important role in the initial interaction with the ligand. Our analysis also shows that Asn53 plays the key role in recognition of acetate pheromones specifically, while Phe12, Phe36, Trp37, Phe76, and Phe118 are responsible for non-specific binding, and Leu8 and Ser9 may play a role in ligand chain length recognition. (C) 2004 Elsevier Ltd. All rights reserved. C1 SUNY Stony Brook, Dept Biochem & Cell Biol, Stony Brook, NY 11794 USA. NIDDK, Phys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Mohanty, S (reprint author), SUNY Stony Brook, Dept Biochem & Cell Biol, Stony Brook, NY 11794 USA. EM smita.mohanty@sunysb.edu OI Gronenborn, Angela M/0000-0001-9072-3525 NR 39 TC 55 Z9 67 U1 1 U2 12 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD MAR 19 PY 2004 VL 337 IS 2 BP 443 EP 451 DI 10.1016/j.jmb.2004.01.009 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 803MW UT WOS:000220236200016 PM 15003458 ER PT J AU Lazzaro, BP Sceurman, BK Clark, AG AF Lazzaro, BP Sceurman, BK Clark, AG TI Genetic basis of natural variation in D-melanogaster antibacterial immunity SO SCIENCE LA English DT Article ID GENOTYPE-ENVIRONMENT INTERACTION; GENOME-WIDE ANALYSIS; EVOLUTION; EXPRESSION; PEPTIDE; RESISTANCE; PROTEINS; FAMILY AB Many genes involved in Drosophila melanogaster innate immune processes have been identified, but whether naturally occurring polymorphism in these genes leads to variation in immune competence among wild flies has not been tested. We report here substantial variability among wild-derived D. melanogaster in the ability to suppress infection by a Gram-negative entomopathogen, Serratia marcescens. Variability in immune competence was significantly associated with nucleotide polymorphism in 16 innate immunity genes, corresponding primarily to pathogen recognition and intracellular signaling loci, and substantial epistasis was detected between intracellular signaling and antimicrobial peptide genes. Variation in these genes, therefore, seems to drive variability in immunocompetence among wild Drosophila. C1 Cornell Univ, Dept Entomol, Ithaca, NY 14853 USA. NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. Cornell Univ, Dept Mol Biol & Genet, Ithaca, NY 14853 USA. RP Lazzaro, BP (reprint author), Cornell Univ, Dept Entomol, 4138 Comstock Hall, Ithaca, NY 14853 USA. EM bl89@cornell.edu FU NIAID NIH HHS [AI46402] NR 24 TC 159 Z9 163 U1 2 U2 26 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD MAR 19 PY 2004 VL 303 IS 5665 BP 1873 EP 1876 DI 10.1126/science.1092447 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 804EI UT WOS:000220281600057 PM 15031506 ER PT J AU Woodson, K Hanson, J Tangrea, J AF Woodson, K Hanson, J Tangrea, J TI A survey of gene-specific methylation in human prostate cancer among black and white men SO CANCER LETTERS LA English DT Article DE gene methylation; prostate cancer; early detection; prognosis ID DNA-BASED DETECTION; B RECEPTOR GENE; SUPPRESSOR GENE; CPG ISLAND; HYPERMETHYLATION; PROGRESSION; PROMOTER; GSTP1; CD44; METASTASIS AB Gene methylation is an important molecular event in prostate carcinogenesis that may have diagnostic and prognostic significance. We evaluated the methylation status of eight genes implicated in prostate carcinogenesis. DNA was extracted from archived paraffin-embedded tumor blocks from 90 prostate cancer patients. Gene methylation status of eight genes (GSTP1, RASSF1A, RARP2, CD44, EDNRB, E-cadherin, Annexin-2, and Caveolin-1) was determined using real-time. methylation-sensitive PCR techniques. Differences in gene methylation among race, tumor grade and disease stage were evaluated by chisquare test. Of the eight genes, GSTP1, RASSF1A, and RARP2 methylation was highly prevalent across tumors (> 60% for all three genes) whereas CD44, E-cadherin and EDNRB methylation was less prevalent (33, 24 and 29%, respectively). Annexin-2 and Caveolin-1 were not methylated in any of the tumors examined. Methylation of RARP2, CD44 and E-cadherin was correlated with tumor grade but not stage. Interestingly, methylation of EDNRB, a gene involved in angiogenesis, was correlated with stage of disease but not tumor grade. With the possible exception of CD44, we did not observe differences in gene methylation between racial categories for the genes under study. In summary, our data suggest that evaluation of the methylation of a panel of genes may have diagnostic and prognostic utility in prostate cancer. (C) 2003 Elsevier Ireland Ltd. All rights reserved. C1 NCI, Ctr Canc Res, Canc Prevent Studies Branch, Bethesda, MD 20892 USA. RP Woodson, K (reprint author), NCI, Ctr Canc Res, Canc Prevent Studies Branch, 6116 Execut blvd,MSC 8314, Bethesda, MD 20892 USA. EM kw114v@nih.gov NR 21 TC 49 Z9 54 U1 0 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD MAR 18 PY 2004 VL 205 IS 2 BP 181 EP 188 DI 10.1016/j.canlet.2003.11.027 PG 8 WC Oncology SC Oncology GA 800OJ UT WOS:000220037300007 PM 15036650 ER PT J AU Bergasa, NV Dersch, CM Rothman, RB AF Bergasa, NV Dersch, CM Rothman, RB TI A study of bile acids as opioid receptor ligands in rat brain membranes SO NEUROSCIENCE LETTERS LA English DT Article DE pruritus; cholestasis; central opioidergic neurotransmission; bile acids; itch; opioid receptors ID ORAL NALTREXONE TREATMENT; DOUBLE-BLIND; SPINAL OPIATES; HUMAN SKIN; PRURITUS; MORPHINE; CHOLESTASIS; LOCALIZATION; RESPONSES AB There is evidence to suggest that the pruritus that results from liver disease is mediated, at least in part, by opioid receptor-ligand interactions; a central component has been proposed. Opiate drugs with agonist activity at opioid receptors induce naloxone-reversible pruritus. Bile acids accumulate in tissues in liver disease. We studied the ability of bile acids to displace specific opioid ligands from opioid receptors in rat and guinea pig brain membrane preparation in binding assays. None of the bile acids studied displaced significantly the opioid ligands from their receptors suggesting that bile acids in vitro are not opioid receptor ligands. The results of this study do not support a role of these bile acids as direct pruritogens by an opioid receptor-mediated mechanism. (C) 2003 Elsevier Ireland Ltd. All rights reserved. C1 Columbia Univ Coll Phys & Surg, Div Digest & Liver Dis, New York, NY 10032 USA. NIDA, Clin Psychopharmacol Sect, Div Intramural Res, NIH, Baltimore, MD 21224 USA. RP Bergasa, NV (reprint author), Columbia Univ Coll Phys & Surg, Div Digest & Liver Dis, 630 W 168th St,P&S 10-508, New York, NY 10032 USA. EM nora.bergasa@downstate.edu NR 25 TC 1 Z9 2 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD MAR 18 PY 2004 VL 358 IS 1 BP 68 EP 70 DI 10.1016/j.neulet.2003.12.103 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 802OF UT WOS:000220172100017 PM 15016436 ER PT J AU Simone, C Stiegler, P Forcales, SV Bagella, L De Luca, A Sartorelli, V Giordano, A Puri, AL AF Simone, C Stiegler, P Forcales, SV Bagella, L De Luca, A Sartorelli, V Giordano, A Puri, AL TI Deacetylase recruitment by the C/H3 domain of the acetyltransferase p300 SO ONCOGENE LA English DT Article DE deacetylases; acetyltransferases; p300; HDAC; transcription ID RNA-POLYMERASE-II; CELL-CYCLE ARREST; HISTONE DEACETYLASE; TRANSCRIPTIONAL CONTROL; REPRESS TRANSCRIPTION; DNA-BINDING; ACETYLATION; MYOD; PROTEINS; CBP AB The balance between acetylation and deacetylation of histone and nonhistone proteins controls gene expression in a variety of cellular processes, with transcription being activated by acetyltransferases and silenced by deacetylases. W e report here the formation and enzymatic characterization of a complex between the acetyltransferase p300 and histone deacetylases. The C/ H3 region of p300 was found to co- purify deacetylase activity from nuclear cell extracts. A prototype of class I histone deacetylases, HDAC1, interacts with p300 C/ H3 domain in vitro and in vivo. The p300- binding protein E1A competes with HDAC1 for C/ H3 binding; and, like E1A, HDAC1 overexpression interferes with either activation of Gal4p300 fusion protein or p300- dependent co- activation of two C/ H3- binding proteins, MyoD and p53. The exposure to deacetylase inhibitors could reverse the dominant- negative effect of a C/ H3 fragment insulated from the rest of the molecule, on MyoD- and p53-dependent transcription, whereas inhibition by E1A was resistant to trichostatin A. The se data support the hypothesis that association between acetyltransferases and deacetylases can control the expression of genes implicated in cellular growth and differentiation, and suggest that the dominant- negative effect of the p300 C/ H3 fragment relies on deacetylase recruitment. C1 Univ Roma La Sapienza, Fdn A Cesalpino, DTI, Gene Express Lab, Rome, Italy. Salk Inst Biol Studies, Peptide Biol Lab, La Jolla, CA 92093 USA. Temple Univ, Coll Sci & Technol, Sbarro Inst Canc Res & Mol Med, Philadelphia, PA 19122 USA. IRCCS Neuromed, I-86077 Pozzilli, IS, Italy. NIAMS, Muscle Biol Lab, Muscle Gene Express Grp, NIH, Bethesda, MD 20892 USA. RP Puri, AL (reprint author), Univ Roma La Sapienza, Fdn A Cesalpino, DTI, Gene Express Lab, Rome, Italy. EM plorenzo@salk.edu RI Forcales, Sonia/B-2157-2013; Giordano, Antonio/F-1927-2010; OI Giordano, Antonio/0000-0002-5959-016X; SIMONE, Cristiano/0000-0002-2628-7658; Forcales, Sonia/0000-0002-7111-4959; Puri, Pier Lorenzo/0000-0003-4964-0095 FU Telethon [GFP01009] NR 64 TC 26 Z9 26 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAR 18 PY 2004 VL 23 IS 12 BP 2177 EP 2187 DI 10.1038/sj.onc.1207327 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 804EB UT WOS:000220280900007 PM 14968110 ER PT J AU Weeraratna, AT Becker, D Carr, KM Duray, PH Rosenblatt, KP Yang, S Chen, YD Bittner, M Strausberg, RL Riggins, GJ Wagner, U Kallioniemi, OP Trent, JM Morin, PJ Meltzer, PS AF Weeraratna, AT Becker, D Carr, KM Duray, PH Rosenblatt, KP Yang, S Chen, YD Bittner, M Strausberg, RL Riggins, GJ Wagner, U Kallioniemi, OP Trent, JM Morin, PJ Meltzer, PS TI Generation and analysis of melanoma SAGE libraries: SAGE advice on the melanoma transcriptome SO ONCOGENE LA English DT Article DE SAGE; melanoma; tissue microarray; CD74; calpain; Wnt5a ID GENE-EXPRESSION; SERIAL ANALYSIS; MALIGNANT-MELANOMA; GASTRIC-CANCER; CELL-LINES; PROTEINS; TUMOR; MUTATIONS; BINDING; FAMILY AB In this study, we generated three SAGE libraries from melanoma tissues. Using bioinformatics tools usually applied to microarray data, we identified several genes, including novel transcripts, which are preferentially expressed in melanoma. SAGE results converged with previous microarray analysis on the importance of intracellular calcium and G- protein signaling, and the Wnt/ Frizzled family. We also examined the expression of CD74, which was specifically, albeit not abundantly, expressed in the melanoma libraries using a melanoma progression tissue microarray, and demonstrate that this protein is expressed by melanoma cells but not by benign melanocytes. Many genes involved in intracellular calcium and G- protein signaling were highly expressed in melanoma, results we had observed earlier from microarray studies ( Bittner et al., 2000). One of the genes most highly expressed in our melanoma SAGE libraries was a calcium-regulated gene, calpain 3 ( p94). Immunohistochemical analysis demonstrated that calpain 3 moves from the nuclei of non- neoplastic cells to the cytoplasm of malignant cells, suggesting activation of this intracellular proteinase. Our SAGE results and the clinical validation data demonstrate how SAGE profiles can highlight specific links between signaling pathways as well as associations with tumor progression. This may provide insights into new genes that may be useful for the diagnosis and therapy of melanoma. C1 NIA, Immunol Lab, NIH, Gerontol Res Ctr, Baltimore, MD 21224 USA. Univ Pittsburgh, Dept Pathol, Pittsburgh, PA USA. NCI, Bethesda, MD 20892 USA. NHGRI, Bethesda, MD 20892 USA. Translat Genom Res Inst, Phoenix, AZ USA. Inst Genom Res, Rockville, MD USA. Johns Hopkins Univ, Dept Neurosurg, Baltimore, MD USA. Univ Basel, Inst Pathol, Basel, Switzerland. Univ Turku, Turku, Finland. Tech Res Ctr Finland, Med Biotechnol Grp, Turku, Finland. RP Weeraratna, AT (reprint author), NIA, Immunol Lab, NIH, Gerontol Res Ctr, 5600 Nathan Shock Dr,Box 21, Baltimore, MD 21224 USA. EM weerarat@grc.nia.nih.gov; pmeltzer@nhgri.nih.gov RI Kallioniemi, Olli/H-5111-2011; Kallioniemi, Olli/H-4738-2012 OI Kallioniemi, Olli/0000-0002-3231-0332; Kallioniemi, Olli/0000-0002-3231-0332 NR 45 TC 49 Z9 49 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAR 18 PY 2004 VL 23 IS 12 BP 2264 EP 2274 DI 10.1038/sj.onc.1207337 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 804EB UT WOS:000220280900017 PM 14755246 ER PT J AU Berman, JJ AF Berman, JJ TI Tumor classification: molecular analysis meets Aristotle SO BMC CANCER LA English DT Article ID SYNOVIAL SARCOMA; GENE; CANCER; HYPOTHESIS; DIAGNOSIS; NEOPLASIA AB Background: Traditionally, tumors have been classified by their morphologic appearances. Unfortunately, tumors with similar histologic features often follow different clinical courses or respond differently to chemotherapy. Limitations in the clinical utility of morphology-based tumor classifications have prompted a search for a new tumor classification based on molecular analysis. Gene expression array data and proteomic data from tumor samples will provide complex data that is unobtainable from morphologic examination alone. The growing question facing cancer researchers is, "How can we successfully integrate the molecular, morphologic and clinical characteristics of human cancer to produce a helpful tumor classification?" Discussion: Current efforts to classify cancers based on molecular features ignore lessons learned from millennia of experience in biological classification. A tumor classification must include every type of tumor and must provide a unique place for each tumor within the classification. Groups within a classification inherit the properties of their ancestors and impart properties to their descendants. A classification was prepared grouping tumors according to their histogenetic development. The classification is simple (reducing the complexity of information received from the molecular analysis of tumors), comprehensive (providing a place for every tumor of man), and consistent with recent attempts to characterize tumors by cytogenetic and molecular features. The clinical and research value of this historical approach to tumor classification is discussed. Summary: This manuscript reviews tumor classification and provides a new and comprehensive classification for neoplasia that preserves traditional nomenclature while incorporating information derived from the molecular analysis of tumors. The classification is provided as an open access XML document that can be used by cancer researchers to relate tumor classes with heterogeneous experimental and clinical tumor databases. C1 NCI, Canc Diag Program, Bethesda, MD 20892 USA. RP Berman, JJ (reprint author), NCI, Canc Diag Program, Bethesda, MD 20892 USA. EM bermanj@mail.nih.gov NR 29 TC 14 Z9 17 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2407 J9 BMC CANCER JI BMC Cancer PD MAR 17 PY 2004 VL 4 AR 10 DI 10.1186/1471-2407-4-10 PG 9 WC Oncology SC Oncology GA 821VU UT WOS:000221491900001 PM 15113444 ER PT J AU Mohiddin, SA Fananapazir, L AF Mohiddin, SA Fananapazir, L TI Myocardial bridging in adult and pediatric patients with hypertrophic cardiomyopathy is not associated with poor outcome SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Letter ID SUDDEN-DEATH; CHILDREN C1 NHLBI, Cardiovasc Branch, NIH, Bethesda, MD 20892 USA. RP Mohiddin, SA (reprint author), NHLBI, Cardiovasc Branch, NIH, Room 7B15,Bldg 10, Bethesda, MD 20892 USA. EM mohiddis@nhlbi.nih.gov NR 3 TC 1 Z9 1 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 17 PY 2004 VL 43 IS 6 BP 1133 EP 1133 DI 10.1016/j.jacc.2003.12.031 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 803DS UT WOS:000220212400037 PM 15028383 ER PT J AU Wacholder, S Chanock, S Garcia-Closas, M El ghormli, L Rothman, N AF Wacholder, S Chanock, S Garcia-Closas, M El ghormli, L Rothman, N TI Assessing the probability that a positive report is false: An approach for molecular epidemiology studies SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID POPULATION STRATIFICATION; CANCER RISK; GENETIC ASSOCIATION; BLADDER-CANCER; DISCOVERY RATE; REPAIR GENES; DISEASE; POLYMORPHISMS; METAANALYSIS; VARIANTS AB Too many reports of associations between genetic variants and common cancer sites and other complex diseases are false positives. A major reason for this unfortunate situation is the strategy of declaring statistical significance based on a P value alone, particularly, any P value below .05. The false positive report probability (FPRP), the probability of no true association between a genetic variant and disease given a statistically significant finding, depends not only on the observed P value but also on both the prior probability that the association between the genetic variant and the disease is real and the statistical power of the test. In this commentary, we show how to assess the FPRP and how to use it to decide whether a finding is deserving of attention or "noteworthy." We show how this approach can lead to improvements in the design, analysis, and interpretation of molecular epidemiology studies. Our proposal can help investigators, editors, and readers of research articles to protect themselves from overinterpreting statistically significant findings that are not likely to signify a true association. An FPRP-based criterion for deciding whether to call a finding noteworthy formalizes the process already used informally by investigators-that is, tempering enthusiasm for remarkable study findings with considerations of plausibility. C1 NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. NCI, Core Genotype Facil, NIH, Bethesda, MD 20892 USA. NCI, Hormonal & Reprod Epidemiol Branch, NIH, Bethesda, MD 20892 USA. NCI, Occupat & Environm Epidemiol Branch, NIH, Bethesda, MD 20892 USA. NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Wacholder, S (reprint author), NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. EM wacholder@nih.gov RI Garcia-Closas, Montserrat /F-3871-2015 OI Garcia-Closas, Montserrat /0000-0003-1033-2650 NR 32 TC 1014 Z9 1035 U1 4 U2 39 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD MAR 17 PY 2004 VL 96 IS 6 BP 434 EP 442 DI 10.1093/jnci/djh075 PG 9 WC Oncology SC Oncology GA 803HH UT WOS:000220221700009 PM 15026468 ER PT J AU Waalkes, MP Liu, J Chen, H Xie, YX Achanzar, WE Zhou, YS Cheng, ML Diwan, BA AF Waalkes, MP Liu, J Chen, H Xie, YX Achanzar, WE Zhou, YS Cheng, ML Diwan, BA TI Estrogen signaling in livers of male mice with hepatocellular carcinoma induced by exposure to arsenic in utero SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID CYCLIN D1 OVEREXPRESSION; RECEPTOR-ALPHA GENE; DRINKING-WATER; BREAST-CANCER; DNA HYPOMETHYLATION; INTERNAL CANCERS; TRANSGENIC MICE; F344/NCR RATS; MOUSE-LIVER; EXPRESSION AB Background: Exposure of pregnant mice to inorganic arsenic induces a spectrum of tumors, including hepatocellular carcinoma (HCC), in their adult offspring similar to that induced by exposing adult mice to estrogenic compounds. To investigate whether arsenic exposure in utero causes altered estrogen signaling, we examined expression of estrogen receptor-alpha (ER-alpha), cyclin D1 (an estrogen-responsive hepatic oncogene), and several cytochrome P450 genes (with sexually dimorphic liver expression patterns) in livers from adult male mice with in utero arsenic-induced HCC. Methods: Quantitative real-time reverse transcription-polymerase chain reaction was used to evaluate gene expression in livers of adult male mice that had (i.e., exposed mice; n = 8) or had not (i.e., control mice; n = 5) been exposed to arsenic in utero. DNA methylation status of portions of the ER-alpha and cyclin D1 gene promoters in liver tissue was measured using methylation-specific polymerase chain reaction. Statistical tests were two-sided. Results: ER-alpha mRNA levels were 3.1-fold (95% confidence interval [CI] = 2.0-fold to 4.3-fold) higher in livers of exposed mice than in those of control mice, and cyclin D1 levels were 3.0-fold (95% CI = 1.7-fold to 4.3-fold) higher. Exposed mice showed a feminized expression pattern of several cytochrome P450 genes, expressing the female-dominant CYP2A4 (P = .017 versus control) and CYP2B9 (P < .001) genes at 8.7 and 10.5 times, respectively, the level in control mice and expressing the male-dominant CYP7B1 at approximately one-fourth the level in control mice (P = .0012). Exposed mice exhibited reduced (by approximately 90%) methylation of the ER-α gene promoter in liver DNA as compared with control mice; the cyclin D1 gene promoter was not methylated in either exposed or control mice. Conclusion: Altered estrogen signaling may play a role in induction of HCC by arsenic exposure in utero. Specifically, overexpression of ER-α, potentially through promoter region hypomethylation, in livers of such mice may be linked to the hepatocarcinogenicity of arsenic. C1 NIEHS, Inorgan Carcinogenesis Sect, Comparat Carcinogenesis Lab, NCI, Res Triangle Pk, NC 27709 USA. SW Prefecture Endem Prevent Stn, Guizhou, Peoples R China. Guiyang Med Coll, Guizhou, Peoples R China. NCI, Basic Res Program, SAIC Frederick, Frederick Canc Res & Dev Ctr, Frederick, MD 21701 USA. RP Waalkes, MP (reprint author), NIEHS, Inorgan Carcinogenesis Sect, Comparat Carcinogenesis Lab, NCI, MD F0-09,111 Alexander Dr, Res Triangle Pk, NC 27709 USA. EM waalkes@niehs.nih.gov FU NCI NIH HHS [N01-CO-12400] NR 61 TC 108 Z9 116 U1 0 U2 9 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD MAR 17 PY 2004 VL 96 IS 6 BP 466 EP 474 DI 10.1093/jnci/djh070 PG 9 WC Oncology SC Oncology GA 803HH UT WOS:000220221700013 PM 15026472 ER PT J AU Steeg, PS AF Steeg, PS TI Metastasis suppressor genes SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID NUCLEOSIDE-DIPHOSPHATE KINASE; PROTEIN-COUPLED RECEPTOR; BREAST-CARCINOMA CELLS; PROSTATE-CANCER METASTASIS; LYMPH-NODE METASTASIS; TUMOR-METASTASIS; NM23 EXPRESSION; MELANOMA-CELLS; GROWTH-FACTOR; IN-VITRO C1 NCI, Womens Canc Sect, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Steeg, PS (reprint author), NCI, Womens Canc Sect, Pathol Lab, NIH, Bldg 10,Rm 2A33, Bethesda, MD 20892 USA. EM steegp@mail.nih.gov NR 77 TC 28 Z9 31 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD MAR 17 PY 2004 VL 96 IS 6 AR E4 DI 10.1093/jnci/djh107 PG 11 WC Oncology SC Oncology GA 803HH UT WOS:000220221700019 PM 15026478 ER PT J AU Murabito, JM Nam, BH D'Agostino, RB Lloyd-Jones, DM O'Donnell, CJ Wilson, PWF AF Murabito, JM Nam, BH D'Agostino, RB Lloyd-Jones, DM O'Donnell, CJ Wilson, PWF TI Accuracy of offspring reports of parental cardiovascular disease history: The Framingham offspring study SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID CORONARY-HEART-DISEASE; HIGH BLOOD CHOLESTEROL; FAMILY-HISTORY; MYOCARDIAL-INFARCTION; RISK FACTOR; ARTERY DISEASE; HYPERTENSION; STROKE; MEN AB Background: Family history is used to infer the risk for heart disease; however, little is known about the accuracy of family history reports. Objective: To examine the accuracy of offspring reports of parental cardiovascular disease. Design: Validation study. Setting: Framingham Heart Study. Participants: Offspring participants of the multigenerational Framingham Heart Study with both parents in the original cohort. Measurements: 791 men and 837 women (mean age, 57 years) completed a family history questionnaire from 1995 to 1998. Offspring reports were compared with confirmed medical evidence of parental status, and positive and negative predictive values and likelihood ratios were calculated. Results: Positive reports of high blood pressure, diabetes, and high cholesterol levels in fathers were accurate: Positive predictive values were 83% (95% CI, 80% to 86%), 76% (CI, 70% to 82%), and 78% (CI, 73% to 83%), respectively. Corresponding positive predictive values for reports in mothers were 91% (Cl, 89% to 93%), 79% (CI, 73% to 85%), and 88% (CI, 84% to 92%), respectively. Positive predictive values for reports of paternal heart attack occurring before 55 years of age and for stroke occurring before 65 years of age were 28% (CI, 22% to 34%) and 43% (CI, 33% to 53%), respectively, whereas the positive likelihood ratios were 8.6 (CI, 6.8 to 10.9) and 11.2 (CI, 9.2 to 13.6), respectively. Negative predictive values for parental history reports were greater than 90%, except for high blood pressure and high cholesterol level (negative predictive values, 33% to 55%, and negative likelihood ratios, 0.47 to 0.88). Limitations: This study does not determine whether more accurate measures of family history would meaningfully improve estimation of cardiovascular risk. Conclusions: Negative parental history reports were reliable, except for hypertension and high cholesterol levels. Although reports of parental premature heart attack and stroke had high likelihood ratios, their predictive values were low because the prevalence of these conditions was low in parents. If patients were more aware of their parents' medical illnesses, they might be able to estimate their risk for disease more accurately and perhaps motivate themselves to follow a healthy lifestye. C1 Framingham Heart Dis Epidemiol Study, NHLBI, Framingham, MA 01702 USA. Boston Univ, Massachusetts Gen Hosp, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NHLBI, Bethesda, MD 20892 USA. RP Murabito, JM (reprint author), Framingham Heart Dis Epidemiol Study, NHLBI, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM Joanne@fram.nhlbi.nih.gov RI Lloyd-Jones, Donald/C-5899-2009 FU NHLBI NIH HHS [N01-HC-25195] NR 30 TC 115 Z9 116 U1 0 U2 2 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD MAR 16 PY 2004 VL 140 IS 6 BP 434 EP 440 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 803AU UT WOS:000220204800004 PM 15023709 ER PT J AU Transue, TR Krahn, JM Gabel, SA DeRose, EF London, RE AF Transue, TR Krahn, JM Gabel, SA DeRose, EF London, RE TI X-ray and NMR characterization of covalent complexes of trypsin, borate, and alcohols SO BIOCHEMISTRY LA English DT Article ID GAMMA-GLUTAMYL-TRANSPEPTIDASE; ACID INHIBITOR COMPLEXES; BORIC-ACID; CRYSTAL-STRUCTURE; SERINE PROTEASES; LIGAND COMPLEXES; TISSUE FACTOR; DRUG DESIGN; BINDING; BORON AB An understanding of the physiological and toxicological properties of borate and the utilization of boronic acids in drug development require a basic understanding of borate-enzyme chemistry. We report here the extension of our recent NMR studies indicating the formation of a ternary borate-alcohol-trypsin complex. Crystallographic and solution state NMR studies of porcine trypsin were performed in the presence of borate and either of three alcohols designed to bind to the S1 affinity subsite: 4-aminobutanol, guanidine-3-propanol, and 4-hydroxymethylbenzamidine. Quaternary complexes of trypsin, borate, SI-binding alcohol, and ethylene glycol (a cryoprotectant), as well as a ternary trypsin, borate, and ethylene glycol complex have been observed in the crystalline state. Borate forms ester bonds to Ser195, ethylene glycol (two bonds), and the SI-binding alcohol (if present). Spectra from (1)H and (11)B NMR studies confirm that these complexes also exist in solution and also provide evidence for the formation of ternary trypsin, borate, and S1-subsite alcohol complexes which are not observed in the crystals using our experimental protocols. Analysis of eight crystal structures indicates that formation of an active site borate complex is in all cases accompanied by a significant (similar to4%) increase in the b-axis dimension of the unit cell. Presumably, our inability to observe the ternary complexes in the crystalline state arises from the lower stability of these complexes and consequent inability to overcome the constraints imposed by the lattice contacts. A mechanism for the coupling of the lattice contacts with the active site that involves a conformational rearrangement of Gln192 is suggested. The structures presented here represent the first crystallographic demonstration of covalent binding of an enzyme by borate. C1 NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP London, RE (reprint author), NIEHS, Struct Biol Lab, NIH, POB 12233,MR-01,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM london@niehs.nih.gov NR 54 TC 33 Z9 33 U1 0 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAR 16 PY 2004 VL 43 IS 10 BP 2829 EP 2839 DI 10.1021/bi035782y PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 802DD UT WOS:000220143300017 PM 15005618 ER PT J AU Eaker, ED Sullivan, LM Kelly-Hayes, M D'Agostino, RB Benjamin, EJ AF Eaker, ED Sullivan, LM Kelly-Hayes, M D'Agostino, RB Benjamin, EJ TI Anger and hostility predict the development of atrial fibrillation in men in the Framingham Offspring Study SO CIRCULATION LA English DT Article DE coronary disease; fibrillation; mortality; men; arrhythmia ID CORONARY-HEART-DISEASE; NONFATAL MYOCARDIAL-INFARCTION; FOLLOW-UP; PSYCHOSOCIAL FACTORS; TOTAL MORTALITY; A BEHAVIOR; CHD INCIDENCE; RISK-FACTORS; ATHEROSCLEROSIS; PHYSICIANS AB Background - Conflicting findings in the literature with regard to the ability of type A behavior, expressions of anger, or hostility to predict incident coronary heart disease ( CHD) have created controversy. In addition, there are no prospective studies relating these characteristics to the development of atrial fibrillation (AF). Methods and Results - From 1984 to 1987, 3873 men and women, 18 to 77 years of age, participating in the Framingham Offspring Study, were examined and monitored for 10 years for the incidence of CHD, AF, and total mortality. Measures of type A behavior, anger, hostility, and risk factors for CHD and AF were collected at the baseline examination. After controlling for age, diabetes, hypertension, history of myocardial infarction, history of congestive heart failure, and valvular heart disease in Cox proportional hazards models, trait-anger (RR = 1.1; 95% CI, 1.0 to 1.4; P = 0.04), symptoms of anger ( RR = 1.2; 95% CI, 1.0 to 1.4; P = 0.008), and hostility ( RR = 1.3; 95% CI, 1.1 to 1.5; P = 0.003) were predictive of 10-year incidence of AF in men. After controlling for risk factors for CHD, none of the measures of anger, type A behavior, or hostility were related to incident CHD; however, trait-anger ( RR = 1.2; 95% CI, 1.1 to 1.4; P < 0.01) was related to total mortality in men. None of the psychosocial variables were related to the 3 outcomes in women. Conclusions - This is the first study to examine and demonstrate a predictive relation between measures of anger and hostility to the development of AF in men. As opposed to type A behavior, measures of anger and hostility may be more productive avenues for research in studying the risk of arrhythmias and total mortality in men. C1 Eaker Epidemiol Enterprises LLC, Chili, WI 54420 USA. Boston Univ, Sch Publ Hlth, Dept Math & Stat, Boston, MA USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Cardiol, Boston, MA 02118 USA. NHLBI, Framingham Heart Study, Bethesda, MD 20892 USA. RP Eaker, ED (reprint author), Eaker Epidemiol Enterprises LLC, 8975 Cty Rd 5, Chili, WI 54420 USA. EM eakerepi@tznet.com OI Sullivan, Lisa/0000-0003-0726-7149; Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [N01-HC-25195, 1-R03-HL-67426-01] NR 36 TC 82 Z9 88 U1 3 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 16 PY 2004 VL 109 IS 10 BP 1267 EP 1271 DI 10.1161/01.CIR.0000118535.15205.8F PG 5 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 803EE UT WOS:000220213600013 PM 14993133 ER PT J AU Min, B Foucras, G Meier-Schellersheim, M Paul, WE AF Min, B Foucras, G Meier-Schellersheim, M Paul, WE TI Spontaneous proliferation, a response of naive CD4 T cells determined by the diversity of the memory cell repertoire SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HOMEOSTATIC PROLIFERATION; POSITIVE SELECTION; TRANSGENIC MICE; MHC COMPLEXES; CUTTING EDGE; IN-VIVO; LYMPHOCYTES; SURVIVAL; RECEPTOR; LIGANDS AB T cell numbers are maintained within narrow ranges in vivo. introduction of naive cells into lymphopenic environments results in proliferation and differentiation driven by the recognition of peptide/MHC complexes and by cytokine signaling. This process, often described as homeostatic proliferation, is here referred to as spontaneous proliferation. We show that, although the presence of memory CD4 T cells of broad repertoire efficiently inhibits proliferation/differentiation of naive CD4 T cells, a memory population of similar size comprised of cells with a repertoire of limited diversity fails to do so, implying that cells of a given specificity prevent responses of cells of the same or related specificity. This finding suggests that the immune system has evolved mechanisms to attain a memory cell repertoire of great diversity independently of foreign antigens. C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. Hop Purpan, Inst Claude Preval, Ctr Physiopathol Toulouse Purpan, INSERM,U 563, F-31059 Toulouse, France. RP Paul, WE (reprint author), NIAID, Immunol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM wpaul@niaid.nih.gov NR 33 TC 100 Z9 103 U1 0 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 16 PY 2004 VL 101 IS 11 BP 3874 EP 3879 DI 10.1073/pnas.0400606101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 804QZ UT WOS:000220314500030 PM 15001705 ER PT J AU Cote-Sierra, J Foucras, G Guo, LY Chiodetti, L Young, HA Hu-Li, J Zhu, JF Paul, WE AF Cote-Sierra, J Foucras, G Guo, LY Chiodetti, L Young, HA Hu-Li, J Zhu, JF Paul, WE TI Interleukin 2 plays a central role in Th2 differentiation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID COLONY-STIMULATING FACTOR; MURINE LYMPHOID-CELLS; CD4(+) T-CELLS; IL-4 PRODUCTION; FLOW CYTOFLUOROMETRY; INTERFERON-GAMMA; GROWTH-HORMONE; GENE; EXPRESSION; PROLACTIN AB Differentiation of naive CD4T cells into T helper (Th)2 cells requires signaling through the T cell receptor and an appropriate cytokine environment. IL-4 is critical for such Th2 differentiation. We show that IL-2 plays a central role in this process. The effect of IL-2 on Th2 generation does not depend on its cell growth or survival effects. Stat5a(-/-) cells show diminished differentiation to IL-4 production, and forced expression of a constitutively active form of Stat5a replaces the need for IL-2. In vivo IL-2 neutralization inhibits IL-4 production in two models. Studies of restriction enzyme accessibility and binding of Stat5 to chromatin indicate that IL-2 mediates its effect by stabilizing the accessibility of the 1/4 gene. Thus, IL-2 plays a critical role in the polarization of naive CD4T cells to the Th2 phenotype. C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. NIAID, Cellular & Mol Immunol Lab, NIH, Bethesda, MD 20892 USA. NCI, Expt Immunol Lab, Ctr Canc Res, Frederick, MD 21702 USA. RP Paul, WE (reprint author), NIAID, Immunol Lab, NIH, Bldg 10,Room 11N311,10 Ctr Dr MSC 1892, Bethesda, MD 20892 USA. EM wpaul@niaid.nih.gov RI Young, Howard/A-6350-2008; Zhu, Jinfang/B-7574-2012 OI Young, Howard/0000-0002-3118-5111; NR 40 TC 185 Z9 189 U1 2 U2 10 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 16 PY 2004 VL 101 IS 11 BP 3880 EP 3885 DI 10.1073/pnas.0400339101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 804QZ UT WOS:000220314500031 PM 15004274 ER PT J AU Wang, SQ Stern, MD Rios, E Cheng, HP AF Wang, SQ Stern, MD Rios, E Cheng, HP TI The quantal nature of Ca2+ sparks and in situ operation of the ryanodine receptor array in cardiac cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID CALCIUM-RELEASE CHANNEL; PHYSIOLOGICAL IONIC CONDITIONS; SKELETAL-MUSCLE; SARCOPLASMIC-RETICULUM; ELEMENTARY EVENTS; HEART-CELLS; CURRENTS; MYOCYTES; UNITS AB Intracellular Ca2+ release in many types of cells is mediated by ryanodine receptor Ca2+ release channels (RyRCs) that are assembled into two-dimensional paracrystalline arrays in the endoplasmic/sarcoplasmic reticulum. However, the in situ operating mechanism of the RyRC array is unknown. Here, we found that the elementary Ca2+ release events, Ca2+ sparks from individual RyRC arrays in rat ventricular myocytes, exhibit quantized Ca2+ release flux. Analysis of the quantal property of Ca2+ sparks provided a view of unitary Ca2+ current and gating kinetics of the RyRC in intact cells and revealed that spark activation involves dynamic recruitment of small, variable cohorts of RyRCs. Intriguingly, interplay of RyRCs in multichannel sparks renders an unusual, thermodynamically irreversible mode of channel gating that is unshared by an RyRC acting solo, nor by RyRCs in vitro. Furthermore, an array-based inhibitory feedback, overriding the regenerative Ca2+-induced Ca2+ release of RyRCs, provides a supramolecular mechanism for the microscopic stability of intracellular Ca2+ signaling. C1 NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. Peking Univ, Natl Lab Biomembrane & Membrane Biotechnol, Beijing 100871, Peoples R China. Rush Univ, Dept Physiol & Mol Biophys, Chicago, IL 60612 USA. RP Cheng, HP (reprint author), NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. EM chengp@grc.nia.nih.gov FU NIAMS NIH HHS [R01 AR032808, R01 AR049184] NR 43 TC 86 Z9 96 U1 0 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 16 PY 2004 VL 101 IS 11 BP 3979 EP 3984 DI 10.1073/pnas.0306157101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 804QZ UT WOS:000220314500048 PM 15004280 ER PT J AU Djousse, L Levy, D Benjamin, EJ Blease, SJ Russ, A Larson, MG Massaro, JM D'Agostino, RB Wolf, PA Ellison, RC AF Djousse, L Levy, D Benjamin, EJ Blease, SJ Russ, A Larson, MG Massaro, JM D'Agostino, RB Wolf, PA Ellison, RC TI Long-term alcohol consumption and the risk of atrial fibrillation in the Framingham Study SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID ADRENERGIC ACTIVITY; CARDIAC-RHYTHM; HEART; ARRHYTHMIAS; DRINKING; DISEASE AB Atrial fibrillation (AF) is a major risk factor for stroke. Although acute alcohol intake has been associated with AF, it is not known whether long-term alcohol consumption in moderation is associated with an increased risk of AF. We used a risk set method to assess the relation of long-term alcohol consumption to the risk of AF among participants in the Framingham Study. For each case, up to 5 controls were selected and matched for age, age at baseline examination, sex, cohort, baseline history of hypertension, congestive heart failure, and myocardial infarction. Within each risk set, alcohol consumption was averaged from baseline until the examination preceding the index case of AF. Of the 1,055 cases of AF occurring during. a follow-up of >50 years, 544 were men and 511 were women. in a conditional logistic regression with additional adjustment for systolic blood pressure, age at baseline examination, education, and cumulative history of myocardial, infarction, congestive heart failure, diabetes mellitus, left ventricular hypertrophy, and valvular heart disease, the relative risks were 1.0 (reference), 0.97 (95% confidence interval [CI] 0.78 to 1.22), 1.06 (95% CI 0.80 to 1.38), 1.12 (95% CI 0.80 to 1.55), and 1.34 (95% CI 1.01 to 1.78) for alcohol categories of 0, 0.1 to 12, 12.1 to 24, 24.1 to 36, and >36 g/day, respectively. In conclusion, our data indicate little association between long-term moderate alcohol consumption and the risk of AF, but a significantly increased risk of AF among subjects consuming >36 g/day (approximatively >3 drinks/day). (C) 2004 by Excerpta Medica, Inc. C1 Boston Univ, Sch Med, Prevent Med & Epidemiol Sect, Evans Dept Med, Boston, MA 02118 USA. NHLBI, Framingham Heart Study, Framingham, MA USA. Boston Univ, Sch Publ Hlth, Dept Neurol, Boston, MA USA. Boston Univ, Dept Math, Boston, MA 02215 USA. RP Djousse, L (reprint author), Boston Univ, Sch Med, Prevent Med & Epidemiol Sect, Evans Dept Med, Room B-612,715 Albany St, Boston, MA 02118 USA. EM ldjousse@bu.edu RI Djousse, Luc/F-5033-2017; OI Djousse, Luc/0000-0002-9902-3047; Ellison, Robert Curtis/0000-0002-0582-7467; Massaro, Joseph/0000-0002-2682-4812; Larson, Martin/0000-0002-9631-1254; Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [5K01 HL70444, N01-HC-38038]; NINDS NIH HHS [5R01-NS-1795] NR 18 TC 119 Z9 121 U1 0 U2 5 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD MAR 15 PY 2004 VL 93 IS 6 BP 710 EP 713 DI 10.1016/j.amjcard.2003.12.004 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 803ML UT WOS:000220235100008 PM 15019874 ER PT J AU Simon, JA Murtaugh, MA Gross, MD Loria, CM Hulley, SB Jacobs, DR AF Simon, JA Murtaugh, MA Gross, MD Loria, CM Hulley, SB Jacobs, DR TI Relation of ascorbic acid to coronary artery calcium - The Coronary Artery Risk Development in Young Adults Study SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE antioxidants; ascorbic acid; calcium; cardiovascular diseases ID CARDIOVASCULAR-DISEASE PREVALENCE; LOW-DENSITY-LIPOPROTEIN; VITAMIN-E CONSUMPTION; HEART-DISEASE; US ADULTS; PROSPECTIVE POPULATION; MYOCARDIAL-INFARCTION; PLASMA-CONCENTRATIONS; ANTIOXIDANT VITAMINS; POSTMENOPAUSAL WOMEN AB Ascorbic acid is an antioxidant nutrient possibly related to the development of atherosclerosis. To examine the relation between ascorbic acid and coronary artery calcium, an indicator of subclinical coronary disease, the authors analyzed data from 2,637 African-American and White men and women aged 18-30 years at baseline who were enrolled in the Coronary Artery Risk Development in Young Adults (CARDIA) Study (1985-2001). Participants completed diet histories at enrollment and year 7, and plasma ascorbic acid levels were obtained at year 10. Coronary artery computed tomography was performed at year 15. The authors calculated odds ratios in four biologically relevant plasma ascorbic acid categories, adjusting for possible confounding variables. When compared with men with high plasma ascorbic acid levels, men with low levels to marginally low levels had an increased prevalence of coronary artery calcium (multivariate odds ratio = 2.68, 95% confidence interval: 1.31, 5.48). Among women, the association was attenuated and nonsignificant (multivariate odds ratio = 1.50, 95% confidence interval: 0.58, 3.85). Ascorbic acid intakes from diet alone and diet plus supplements were not associated with coronary artery calcium. Low to marginally low plasma ascorbic acid levels were associated with a higher prevalence of coronary artery calcium among men but not among women. C1 Vet Affairs Med Ctr, Med Serv, Gen Internal Med Sect, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Univ Utah, Sch Med, Dept Family & Prevent Med, Salt Lake City, UT 84112 USA. Univ Minnesota, Sch Publ Hlth, Div Epidemiol, Minneapolis, MN 55455 USA. NHLBI, NIH, Bethesda, MD 20892 USA. Univ Oslo, Inst Nutr Res, Oslo, Norway. RP Simon, JA (reprint author), San Francisco VA Med Ctr, Gen Internal Med Sect 111A1, 4150 Clement St, San Francisco, CA 94121 USA. EM jasimon@itsa.ucsf.edu OI Murtaugh, Maureen/0000-0001-5281-0302 FU NHLBI NIH HHS [HC 48047, HC 48048, HC 48049, HC 48050, HL 53359] NR 37 TC 16 Z9 17 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD MAR 15 PY 2004 VL 159 IS 6 BP 581 EP 588 DI 10.1093/aje/kwh079 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 802RM UT WOS:000220180600007 PM 15003962 ER PT J AU Samelson, EJ Kiel, DP Broe, KE Zhang, YQ Cupples, LA Hannan, MT Wilson, PWF Levy, D Williams, SA Vaccarino, V AF Samelson, EJ Kiel, DP Broe, KE Zhang, YQ Cupples, LA Hannan, MT Wilson, PWF Levy, D Williams, SA Vaccarino, V TI Metacarpal cortical area and risk of coronary heart disease - The Framingham Study SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE bone and bones; coronary disease; incidence; osteoporosis; prospective studies ID BONE-MINERAL DENSITY; POSTMENOPAUSAL WOMEN; HIP FRACTURE; OSTEOPOROTIC FRACTURES; AORTIC CALCIFICATION; ELDERLY-WOMEN; MASS; MEN; MENOPAUSE; MORTALITY AB The objective of this study was to determine the relation between bone mass and the incidence of coronary heart disease in women and men. Participants included 2,059 cohort members of the Framingham Study (1,236 women and 823 men aged 47-80 years) who underwent posteroanterior hand radiography and were free from cardiovascular disease at baseline (1967-1970) and who were then followed for 30 years through the end of 1997 for the incidence of coronary heart disease. The incidence of coronary heart disease decreased from 15.65/1,000 person-years among women in the lowest metacarpal cortical area quartile to 11.76/1,000 person-years among women in the highest quartile (p(trend) = 0.03), and the inverse relation persisted after adjustment for confounders (highest vs. lowest quartile of metacarpal cortical area: hazard ratio = 0.73, 95% confidence interval: 0.53, 1.00; p(trend) = 0.03). In contrast, no association was present in men (highest vs. lowest quartile of metacarpal cortical area: hazard ratio = 1.14, 95% confidence interval: 0.84, 1.56; p(trend) = 0.55). C1 Hebrew Rehabil Ctr Aged, Res & Training Inst, Boston, MA 02131 USA. Harvard Univ, Sch Med, Div Aging, Boston, MA 02115 USA. Boston Univ, Sch Med, Clin Epidemiol Res & Training Unit, Boston, MA 02118 USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. Framingham Heart Dis Epidemiol Study, Boston, MA USA. NHLBI, Bethesda, MD 20892 USA. AstraZeneca LP, Wilmington, DE USA. Emory Sch Med, Dept Med, Div Cardiol, Atlanta, GA USA. Rollins Sch Publ Hlth, Atlanta, GA USA. RP Samelson, EJ (reprint author), Hebrew Rehabil Ctr Aged, Res & Training Inst, 1200 Ctr St, Boston, MA 02131 USA. EM samelson@mail.hrca.harvard.edu OI Cupples, L. Adrienne/0000-0003-0273-7965; Zhang, Yuqing/0000-0001-7954-1149; Kiel, Douglas/0000-0001-8474-0310 FU NHLBI NIH HHS [N01 HC 38038]; NIAMS NIH HHS [R01 AR/AG 41398] NR 49 TC 60 Z9 65 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD MAR 15 PY 2004 VL 159 IS 6 BP 589 EP 595 DI 10.1093/aje/kwh080 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 802RM UT WOS:000220180600008 PM 15003963 ER PT J AU Deng, JP Hu, XZ Yuen, PST Star, RA AF Deng, JP Hu, XZ Yuen, PST Star, RA TI alpha-melanocyte-stimulating hormone inhibits lung injury after renal ischemia/reperfusion SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE inflammation; nuclear factor-kappa B; p38; leukocytes; intracellular adhesion molecule-1; tumor necrosis factor-alpha ID NF-KAPPA-B; ISCHEMIA-REPERFUSION INJURY; NECROSIS-FACTOR-ALPHA; P38 MAP KINASE; EXPERIMENTAL BRAIN INFLAMMATION; ACTIVATED PROTEIN-KINASE; DNA-BINDING; MOLECULAR-MECHANISMS; PULMONARY-EDEMA; RAT LUNG AB Combined acute renal and pulmonary failure has a very high mortality. In animals, lung injury develops after shock or visceral or renal ischemia. a-Melanocyte-stimulating hormone (alpha-MSH) is an anti-inflammatory cytokine, which inhibits inflammatory, apoptotic, and cytotoxic pathways implicated in acute renal injury. We sought to determine if a-MSH inhibits acute lung injury after renal ischemia and to determine the early mechanisms of alpha-MSH action. Mice were subjected to renal ischemia treated with vehicle or alpha-MSH. At early time points, we measured organ histology, leukocyte accumulation, myeloperoxidase activity, activation of nuclear factor-kappaB, p38 mitogen-activated protein kinase, c-Jun, and activator protein-1 pathways, in addition to messenger RNA for intracellular adhesion molecule-1 and tumor necrosis factor-alpha. Renal ischemia rapidly activated kidney and lung nuclear factor-kappaB, p38 mitogen-activated protein kinase, c-Jun, and activator protein-1 pathways, and distant lung injury. a-MSH administration immediately before reperfusion significantly decreased kidney and lung injury and prevented activation of kidney and lung transcription factors and stress response genes, and lung intracellular adhesion molecule-1 and tumor necrosis factor-a at early time points after renal ischemia/reperfusion. We conclude that distant lung injury occurs rapidly after renal ischemia. a-MSH protects against both kidney and lung damage after renal ischemia, in part, by inhibiting activation of transcription factors and stress genes early after renal injury. C1 NIDDKD, Renal Diagnost & Therapeut Unit, NIH, Bethesda, MD 20892 USA. RP Star, RA (reprint author), NIDDKD, Renal Diagnost & Therapeut Unit, NIH, Bldg 10,Room 3N108,10 Ctr Dr, Bethesda, MD 20892 USA. EM Robert_Star@nih.gov RI Yuen, Peter/B-1954-2008 OI Yuen, Peter/0000-0001-9557-3909 NR 70 TC 78 Z9 83 U1 0 U2 2 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR 15 PY 2004 VL 169 IS 6 BP 749 EP 756 DI 10.1164/rccm.200303-372OC PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 802YP UT WOS:000220199100017 PM 14711793 ER PT J AU Vistica, J Dam, J Balbo, A Yikilmaz, E Mariuzza, RA Rouault, TA Schuck, P AF Vistica, J Dam, J Balbo, A Yikilmaz, E Mariuzza, RA Rouault, TA Schuck, P TI Sedimentation equilibrium analysis of protein interactions with global implicit mass conservation constraints and systematic noise decomposition SO ANALYTICAL BIOCHEMISTRY LA English DT Article DE protein interactions; heterogeneous association; protein complexes; analytical ultracentrifugation; molar mass distribution ID MOLECULAR-WEIGHT DISTRIBUTION; RAYLEIGH INTERFERENCE OPTICS; SIZE-DISTRIBUTION ANALYSIS; ANALYTICAL ULTRACENTRIFUGATION; QUANTITATIVE-ANALYSIS; INTEGRAL-EQUATIONS; CRYSTAL-STRUCTURE; SELF-ASSOCIATION; LEAST-SQUARES; HIGH-AFFINITY AB Sedimentation equilibrium is a powerful tool for the characterization of protein self-association and heterogeneous protein interactions. Frequently, it is applied in a configuration with relatively long solution columns and with equilibrium profiles being acquired sequentially at several rotor speeds. The present study proposes computational tools, implemented in the software SEDPHAT, for the global analysis of equilibrium data at multiple rotor speeds with multiple concentrations and multiple optical detection methods. The detailed global modeling of such equilibrium data can be a nontrivial computational problem. It was shown previously that mass conservation constraints can significantly improve and extend the analysis of heterogeneous protein interactions. Here, a method for using conservation of mass constraints for the macromolecular redistribution is proposed in which the effective loading concentrations are calculated from the sedimentation equilibrium profiles. The approach is similar to that described by Roark (Biophys. Chem. 5 (1976) 185-196), but its utility is extended by determining the bottom position of the solution columns from the macromolecular redistribution. For analyzing heterogeneous associations at multiple protein concentrations, additional constraints that relate the effective loading concentrations of the different components or their molar ratio in the global analysis are introduced. Equilibrium profiles at multiple rotor speeds also permit the algebraic determination of radial-dependent baseline profiles, which can govern interference optical ultracentrifugation data, but usually also occur, to a smaller extent, in absorbance optical data. Finally, the global analysis of equilibrium profiles at multiple rotor speeds with implicit mass conservation and computation of the bottom of the solution column provides an unbiased scale for determining molar mass distributions of non-interacting species. The properties of these tools are studied with theoretical and experimental data sets. (C) 2004 Elsevier Inc. All rights reserved. C1 NIH, Div Bioengn & Phys Sci, ORS, OD, Bethesda, MD 20892 USA. Univ Maryland, Inst Biotechnol, Ctr Adv Res Biotechnol, Rockville, MD USA. NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Schuck, P (reprint author), NIH, Div Bioengn & Phys Sci, ORS, OD, Bethesda, MD 20892 USA. EM pschuck@helix.nih.gov OI Dam, Julie/0000-0001-6871-2678; Schuck, Peter/0000-0002-8859-6966 NR 61 TC 231 Z9 231 U1 0 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD MAR 15 PY 2004 VL 326 IS 2 BP 234 EP 256 DI 10.1016/j.ab.2003.12.014 PG 23 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 803BX UT WOS:000220207700012 PM 15003564 ER PT J AU Baczek, T Bucinski, A Ivanov, AR Kaliszan, R AF Baczek, T Bucinski, A Ivanov, AR Kaliszan, R TI Artificial neural network analysis for evaluation of peptide MS/MS spectra in proteomics SO ANALYTICAL CHEMISTRY LA English DT Article ID 2-DIMENSIONAL GEL-ELECTROPHORESIS; AMINO-ACID-SEQUENCES; MASS-SPECTROMETRY; LIQUID-CHROMATOGRAPHY; PROTEIN DATABASE; SACCHAROMYCES-CEREVISIAE; YEAST PROTEOME; IDENTIFICATION; RETENTION; CORRELATE AB The aim of the work was to explore usefulness of artificial neural network (ANN) analysis for the evaluation of proteomics data. The analysis was applied to the data generated by the widely used protein identification program Sequest, completed with several structural parameters readily calculated from peptide molecular formulas. Proteins from yeast cells were identified based on the MS/ MS spectra of peptides. The constructed ANN was demonstrated to classify automatically as either "good" or "bad" the peptide MS/MS spectra otherwise classified manually. An appropriately trained ANN proves to be a high-throughput tool facilitating examination of Sequest's results. ANNs are recommended as a means of automatic processing of large amounts of MS/MS data, which normally must be considered in the analysis of complex mixtures of proteins in proteomics. C1 Med Univ Gdansk, Dept Biopharmaceut & Pharmacodynam, PL-80416 Gdansk, Poland. Polish Acad Sci, Div Food Sci, Inst Anim Reprod & Food Res, PL-10747 Olsztyn, Poland. Harvard Univ, Sch Publ Hlth, Harvard NIEHS Ctr Environm Hlth & Proteom Facil, Boston, MA 02115 USA. RP Baczek, T (reprint author), Med Univ Gdansk, Dept Biopharmaceut & Pharmacodynam, Gen J Hallera 107, PL-80416 Gdansk, Poland. EM tbaczek@amg.gda.pl RI Kaliszan, Roman/E-4784-2011; Bucinski, Adam/F-5565-2014 NR 53 TC 49 Z9 50 U1 2 U2 11 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD MAR 15 PY 2004 VL 76 IS 6 BP 1726 EP 1732 DI 10.1021/ac030297u PG 7 WC Chemistry, Analytical SC Chemistry GA 803IQ UT WOS:000220225200026 PM 15018575 ER PT J AU Suzuki-Inoue, K Wilde, JI Andrews, RK Auger, JM Siraganian, RP Sekiya, F Rhee, SG Watson, SP AF Suzuki-Inoue, K Wilde, JI Andrews, RK Auger, JM Siraganian, RP Sekiya, F Rhee, SG Watson, SP TI Glycoproteins VI and Ib-IX-V stimulate tyrosine phosphorylation of tyrosine kinase Syk and phospholipase C gamma 2 at distinct sites SO BIOCHEMICAL JOURNAL LA English DT Article DE blood platelet; collagen; glycoprotein VI (GPVI); glycoprotein Ib-IX-V (GPIb-IX-V); phospholipase C gamma 2 (PLC gamma 2); von Willebrand factor (vWF) ID RECEPTOR-GAMMA-CHAIN; VON-WILLEBRAND-FACTOR; B-CELL; HUMAN PLATELETS; DEPENDENT PHOSPHORYLATION; ACTIVATION; COLLAGEN; BTK; INVOLVEMENT; C-GAMMA-2 AB Glycoproteins GPVI and GPlb-IX-V stimulate robust tyrosine phosphorylation of Syk and PLCgamma2 (phospholipase Cgamma2) in washed platelets, but only the former stimulates pronounced activation of phospholipase. Using phospho-specific antibodies, we demonstrate that GPVI, but not GPlb-IX-V, stimulates significant tyrosine phosphorylation of Syk at the autophosphorylation site pY525/526, a marker of Syk activity. In addition, GPVI stimulates tyrosine phosphorylation of PLCgamma2 at Tyr(753) and Tyr(759), whereas GPIb-IX-V only induces significant phosphorylation at Tyr(753). Both receptors stimulate tyrosine phosphorylation of Btk at the regulatory Tyr(223) and Tyr(551). Syk and Btk phosphorylate peptides from PLCgamma2 containing Tyr(753) and Tyr(759) respectively, suggesting that they may stimulate phosphorylation at these sites in phospholipase. Studies using PLCgamma2-deficient platelets demonstrated that phospholipase is not required for the activation of integrin aIIbbeta3 by GPIb-IX-V. Our results demonstrate fundamental differences between GPVI and GPIb-IX-V in the regulation of tyrosine phosphorylation of Syk and PLCgamma2 consistent with the functional impairment of phospholipase in signalling by GPIb-IX-V. C1 Univ Oxford, Dept Pharmacol, Oxford OX1 3QT, England. Med Sch Edgbaston, Div Med Sci, Birmingham B15 2TT, W Midlands, England. Natl Inst Dent & Craniofacial Res, Receptors & Signal Transduct Sect, NIH, Bethesda, MD 20892 USA. NHLBI, Lab Cell Signaling, NIH, Bethesda, MD 20892 USA. RP Suzuki-Inoue, K (reprint author), Univ Yamanashi, Fac Med, Clin & Lab Med, Yamanashi 4093898, Japan. EM katsuei@yamanashi.ac.jp RI Watson, Stephen/Q-6292-2016 OI Watson, Stephen/0000-0002-7846-7423 NR 29 TC 33 Z9 34 U1 0 U2 0 PU PORTLAND PRESS PI LONDON PA 59 PORTLAND PLACE, LONDON W1N 3AJ, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD MAR 15 PY 2004 VL 378 BP 1023 EP 1029 DI 10.1042/BJ20031430 PN 3 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 807DB UT WOS:000220481100037 PM 14656219 ER PT J AU Kinyamu, HK Archer, TK AF Kinyamu, HK Archer, TK TI Modifying chromatin to permit steroid hormone receptor-dependent transcription SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION LA English DT Review DE steroid hormone receptor; chromatin; chromatin remodeling; histone modification; proteasome; transcription ID TUMOR VIRUS PROMOTER; HUMAN BREAST-CANCER; MAMMALIAN SWI/SNF COMPLEXES; TATA-BINDING PROTEIN; LONG TERMINAL REPEAT; LINKER HISTONE H1; ESTROGEN-RECEPTOR; NUCLEAR RECEPTOR; GLUCOCORTICOID-RECEPTOR; ANDROGEN RECEPTOR AB Lipophilic hormones, including steroids, exert their physiological effects through binding to high-affinity superfamily of steroid hormone receptor (SR) proteins that function as ligand-dependent DNA binding transcription factors. To date, SR proteins are among a few transcription factors shown to directly interact with higher order chromatin structures to regulate gene expression. To perturb chromatin, SRs employ enzymatic multicomplexes that can either remodel or modify chromatin. Here we examine the current state of knowledge concerning multicomplex chromatin remodeling/modification machines and SR-dependent transcription. We will focus on the role of these protein-protein and chromatin-protein interactions in vivo with the MMTV promoter as a primary model. In addition, we discuss emerging evidence implicating chaperone proteins and proteasome degradation machinery in SR-mediated gene regulation within chromatin. Published by Elsevier B.V. C1 NIEHS, Chromatin & Gene Express Sect, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Archer, TK (reprint author), NIEHS, Chromatin & Gene Express Sect, Mol Carcinogenesis Lab, NIH, POB 12233 MD E4-06,111 Alexander Dr, Res Triangle Pk, NC 27709 USA. EM archer1@niehs.nih.gov NR 212 TC 52 Z9 54 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4781 J9 BBA-GENE STRUCT EXPR JI Biochim. Biophys. Acta-Gene Struct. Expression PD MAR 15 PY 2004 VL 1677 IS 1-3 BP 30 EP 45 DI 10.1016/j.bbaexp.2003.09.015 PG 16 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 804YJ UT WOS:000220333700005 PM 15020043 ER PT J AU Hager, GL Nagaich, AK Johnson, TA Walker, DA John, S AF Hager, GL Nagaich, AK Johnson, TA Walker, DA John, S TI Dynamics of nuclear receptor movement and transcription SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE STRUCTURE AND EXPRESSION LA English DT Review DE nucleus; nuclear receptor; dynamics; chromatin; transcription; cycling ID LIVING CELLS; ESTROGEN-RECEPTOR; GLUCOCORTICOID-RECEPTOR; COACTIVATOR COMPLEXES; IN-VIVO; ORDERED RECRUITMENT; RAPID EXCHANGE; CHROMATIN; PROMOTER; PROTEINS AB Following a hormone signal, steroid/nuclear receptors bind regulatory elements in chromatin and initiate the recruitment of a variety of multi-protein complexes to promoter sequences. These complexes ultimately lead to the recruitment of general transcription factors and the initiation of transcription. Traditional models suggest that these factors remain statically bound to each other and to chromatin until other signals are received to reduce transcription. Recent findings demonstrate that the processes and actions involved are much more complex than traditional models convey, and that the movement of receptors and coactivators is remarkably dynamic. Transcription factors are highly mobile in the nuclear environment, and interact only briefly with target sites in the nucleus. As a result of these transient interactions, promoters move through many states during activation and repression. Two general concepts emerge from current data: (1) Various transcription factors appear to follow "ordered recruitment" to promoters on a time scale of minutes to hours in response to a stimulus. During this response, the proteins that interact with chromatin may cycle on and off the promoter multiple times. (2) During these ordered recruitment cycles, the individual molecules that form functional complexes often exchange rapidly on a time scale of seconds. This rapid exchange of molecules within a formed complex occurs independently of long-term cycling on chromatin. Several processes are implicated in rapid nuclear dynamics, including potential roles for molecular chaperones, the proteasome degradation machinery and chromatin remodeling complexes. (C) 2004 Elsevier B.V. C1 NCI, Lab Receptor Biol & Gene Express, Bethesda, MD 20892 USA. RP Hager, GL (reprint author), NCI, Lab Receptor Biol & Gene Express, Bldg 41,Room B602,41 Lib Dr MSC 5055, Bethesda, MD 20892 USA. EM hagerg@dce41.nei.nih.gov NR 34 TC 70 Z9 70 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4781 J9 BBA-GENE STRUCT EXPR JI Biochim. Biophys. Acta-Gene Struct. Expression PD MAR 15 PY 2004 VL 1677 IS 1-3 BP 46 EP 51 DI 10.1016/j.bbaexp.2003.09.016 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 804YJ UT WOS:000220333700006 PM 15020044 ER PT J AU Hamidi, M Drevets, WC Price, JL AF Hamidi, M Drevets, WC Price, JL TI Glial reduction in amygdala in major depressive disorder is due to oligodendrocytes SO BIOLOGICAL PSYCHIATRY LA English DT Article DE stereology; S-100 beta; human leukocyte antigen; astrocyte; microglia; bipolar disorder ID DORSOLATERAL PREFRONTAL CORTEX; FIBRILLARY ACIDIC PROTEIN; SEVERE MENTAL-ILLNESS; BIPOLAR DISORDER; MOOD DISORDERS; GLUCOSE-METABOLISM; FRONTAL-CORTEX; NEURONAL SIZE; CELL DENSITY; BRAIN AB Background: A previous study reported reductions in glial density and glia/neuron ratio in the amygdala of individuals with major depressive disorder (MDD), without a change in neuronal density. It is not known, however, whether this glial loss is due to astrocytes, oligodendrocytes, or microglia. Methods: Tissue samples, equally from the tight and left hemispheres, were obtained from subjects diagnosed with MDD (n = 8), bipolar disorder (BD) (h = 9), or no psychiatric disorders (n = 10). Sections were stained immunohistochemically for S-100beta (for astrocytes) and human leukocyte antigen (for microglia), and with the Nissl method. in Nissl-stained sections, oligodendrocytes have more compact, darker-stained nuclei, whereas astrocytes and microglia have larger, lighter-stained nuclei, with more granular chromatin. Neurons are larger, with a nucleolus and stained cytoplasm. The density of glia was determined with stereologic methods. Results: The density of total glia and oligodendrocytes in the amygdala was significantly lower in MDD than in control subjects, but not significantly lower in BD compared with control subjects. The decreases were largely accounted for by differences in the left hemisphere. There was no significant decrease in astrocyte or microglia density in MDD or BD subjects. Conclusions: The glial cell reduction previously found in the amygdala in MDD is primarily due to oligodendrocytes. C1 Washington Univ, Sch Med, Dept Anat & Neurobiol, St Louis, MO 63110 USA. NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. RP Price, JL (reprint author), Washington Univ, Sch Med, Dept Anat & Neurobiol, Campus Box 8108,660 S Euclid Ave, St Louis, MO 63110 USA. OI Hamidi, Massihullah/0000-0002-5470-6565 FU NIDCD NIH HHS [DC000093]; NIMH NIH HHS [MH01713] NR 60 TC 187 Z9 201 U1 1 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAR 15 PY 2004 VL 55 IS 6 BP 563 EP 569 DI 10.1016/j.biopsych.2003.11.006 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 801PZ UT WOS:000220109100002 PM 15013824 ER PT J AU Bremner, JD Vermetten, E Vythilingam, M Afzal, N Schmahl, C Elzinga, B Charney, DS AF Bremner, JD Vermetten, E Vythilingam, M Afzal, N Schmahl, C Elzinga, B Charney, DS TI Neural correlates of the classic color and emotional stroop in women with abuse-related posttraumatic stress disorder SO BIOLOGICAL PSYCHIATRY LA English DT Article DE posttraumatic stress disorder; Stroop; emotion; fear; amygdala; hippocampus; anxiety ID POSITRON-EMISSION-TOMOGRAPHY; ANTERIOR CINGULATE CORTEX; MEDIAL PREFRONTAL CORTEX; CHILDHOOD SEXUAL-ABUSE; SCRIPT-DRIVEN IMAGERY; SYMPTOM PROVOCATION; FUNCTIONAL MRI; RAPE VICTIMS; THREAT CUES; PTSD AB Background: The anterior cingulate and medial prefrontal cortex play an important role in the inhibition of responses, as measured by the Stroop task, as well as in emotional regulation. Dysfunction of the anterior cingulate/medial prefrontal cortex has been implicated in posttraumatic stress disorder (PTSD). The purpose of this study was to use the Stroop task as a probe of anterior cingulate function in PTSD. Methods: Women with early childhood sexual abuse-related PTSD (n = 12) and women with abuse but without PTSD (n = 9) underwent positron emission tomograpbic measurement of cerebral blood flow during exposure to control, color Stroop, and emotional Stroop conditions. Results: Women with abuse with PTSD (but not abused non-PTSD women) had a relative decrease in anterior cingulate blood flow during exposure to the emotional (but not color) classic Stroop task. During the color Stroop there were also relatively greater increases in blood flow in non-PTSD compared with PTSD women in right visual association cortex, cuneus, and right inferior parietal lobule. Conclusions. These findings add further evidence for dysfunction of a network of brain regions, including anterior cingulate and visual and parietal cortex, in abuse-related PTSD. C1 Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA 30322 USA. Emory Univ, Sch Med, Dept Radiol, Atlanta, GA 30322 USA. Emory Univ, Sch Med, Atlanta Vet Affairs Med Ctr, Atlanta, GA 30322 USA. NIMH, Mood & Anxiety Disorders Res Program, Bethesda, MD 20892 USA. RP Bremner, JD (reprint author), Emory Univ, Emory Clin Neurosci Res Unit, Emory W Campus,1256 Briarcliff Rd, Atlanta, GA 30306 USA. RI Bremner, James/B-1632-2013; Schmahl, C/E-8760-2012; OI Vermetten, Eric/0000-0003-0579-4404 FU NIMH NIH HHS [R01 MH56120] NR 53 TC 141 Z9 148 U1 7 U2 32 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAR 15 PY 2004 VL 55 IS 6 BP 612 EP 620 DI 10.1016/j.biopsych.2003.10.001 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 801PZ UT WOS:000220109100008 PM 15013830 ER PT J AU Potenza, MN Brodkin, ES Joe, B Luo, XG Remmers, EF Wilder, RL Nestler, EJ Gelernter, J AF Potenza, MN Brodkin, ES Joe, B Luo, XG Remmers, EF Wilder, RL Nestler, EJ Gelernter, J TI Genomic regions controlling corticosterone levels in rats SO BIOLOGICAL PSYCHIATRY LA English DT Article DE stress; addiction; Fischer 344; Lewis; Dark Agouti (DA); genetics; quantitative trait loci; hypothalamic-pituitary-adrenal axis; congenic; drug dependence ID COLLAGEN-INDUCED ARTHRITIS; QUANTITATIVE TRAIT LOCI; CORTICOTROPIN-RELEASING-FACTOR; PITUITARY-ADRENAL AXIS; NEUROPEPTIDE-Y; RHEUMATOID-ARTHRITIS; ALCOHOL DEPENDENCE; BEHAVIORAL-RESPONSES; AUTOIMMUNE-DISEASE; GENETIC DISSECTION AB Background: The identification of genetic,factors controlling stress-responsiveness should advance the understanding of susceptibility to psychiatric illness. Methods: Rat strains, F344/NHsd and LEW/NHsd, which differ in measures of stress-responsiveness and behaviors modeling psychiatric disorders, were bred to generate F, progeny that were used in a quantitative trait loci QTL) analysis to identify genomic regions influencing late-afternoon corticosterone levels. Results: Regions on chromosomes 4 and 10 previously identified as influencing autoimmune phenomena were the most significant QTL observed, reaching suggestive significance at the genome-wide level. Congenic animals targeting these regions with F344/NHsd deoxyribonucleic acid on a DA/Bkl genomic background demonstrated corticosterone levels approximating those of F344/NHsd rats and differing significantly from DA/Bkl rats. Conclusions: Specific genomic regions influence both corticosterone levels and stress-related disease susceptibility. These findings not only represent the first identification of QTL controlling corticosterone levels but also suggest a mechanism underlying genetic differences in stress-responsiveness. C1 Yale Univ, Sch Med, Connecticut Mental Hlth Ctr, Dept Psychiat, New Haven, CT 06519 USA. Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Ctr Neurobiol & Behav, Philadelphia, PA 19104 USA. NIAMSD, NIH, Bethesda, MD 20892 USA. Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX 75230 USA. Univ Texas, SW Med Ctr, Ctr Basic Neurosci, Dallas, TX 75230 USA. RP Potenza, MN (reprint author), Yale Univ, Sch Med, Connecticut Mental Hlth Ctr, Dept Psychiat, Room S-104,34 Pk St, New Haven, CT 06519 USA. FU NIAAA NIH HHS [R01 AA11330]; NIDA NIH HHS [K12-DA00366, R01 DA12849, K12-DA00167, P01 DA08227] NR 38 TC 18 Z9 21 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD MAR 15 PY 2004 VL 55 IS 6 BP 634 EP 641 DI 10.1016/j.biopsych.2003.11.005 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 801PZ UT WOS:000220109100011 PM 15013833 ER PT J AU Roberts, JL Lengi, A Brown, SM Chen, M Zhou, YJ O'Shea, JJ Buckley, RH AF Roberts, JL Lengi, A Brown, SM Chen, M Zhou, YJ O'Shea, JJ Buckley, RH TI Janus kinase 3 (JAK3) deficiency: clinical, immunologic, and molecular analyses of 10 patients and outcomes of stem cell transplantation SO BLOOD LA English DT Article ID SEVERE COMBINED IMMUNODEFICIENCY; INTERLEUKIN-2-RECEPTOR GAMMA-CHAIN; COMBINED IMMUNE-DEFICIENCY; IL-2 RECEPTOR; TYROSINE KINASE; GENE-THERAPY; FERM DOMAIN; FUNCTIONAL COMPONENT; SIGNAL-TRANSDUCTION; PSEUDOKINASE DOMAIN AB We found 10 individuals from 7 unrelated families among 170 severe combined immunodeficiency (SCID) patients who exhibited 9 different Janus kinase 3 (JAK3) mutations. These included 3 missense and 2 nonsense mutations, 1 insertion, and 3 deletions. With the exception of 1 individual with persistence of transplacentally transferred maternal lymphocytes, ail infants presented with a T(-)B(+)NK(-)phenotype. The patient mutations all resulted in abnormal B-cell Janus kinase 3 (JAK3)-dependent interleukin-2 (IL-2)-induced signal transducer and activator of transcription-5 (STAT5) phosphorylation. Additional analyses of mutations permitting protein expression revealed the N-terminal JH7 (del58A) and JH6 (D169E) domain mutations each inhibited receptor binding and catalytic activity, whereas the G589S JH2 mutation abrogated kinase activity but did not affect gammac association. Nine of the 10 patients are currently alive from between 4 years and 18 years following stem cell transplantation, with all exhibiting normal T-cell function. Reconstitution of antibody function was noted in only 3 patients. Natural killer (NK) function was severely depressed at presentation in the 4 patients studied, whereas after transplantation the only individuals with normal NK lytic activity were patients 1 and 5. Hence, bone marrow transplantation is an effective means for reconstitution of T-cell immunity in this defect but is less successful for restoration of B-cell and NK cell functions. (C) 2004 by The American Society of Hematology. C1 Duke Univ, Med Ctr, Dept Pediat, Durham, NC 27710 USA. NIAMSD, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA. RP Roberts, JL (reprint author), Duke Univ, Med Ctr, Dept Pediat, Box 2898, Durham, NC 27710 USA. EM rober060@mc.duke.edu FU NCRR NIH HHS [M01-RR-30]; NIAID NIH HHS [AI42951, AI47605]; NICHD NIH HHS [HD35961] NR 72 TC 59 Z9 64 U1 2 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAR 15 PY 2004 VL 103 IS 6 BP 2009 EP 2018 DI 10.1182/blood-2003-06-2104 PG 10 WC Hematology SC Hematology GA 801VM UT WOS:000220123400014 PM 14615376 ER PT J AU Turville, SG Santos, JJ Frank, I Cameron, PU Wilkinson, J Miranda-Saksena, M Dable, J Stossel, H Romani, N Piatak, M Lifson, JD Pope, M Cunningham, AL AF Turville, SG Santos, JJ Frank, I Cameron, PU Wilkinson, J Miranda-Saksena, M Dable, J Stossel, H Romani, N Piatak, M Lifson, JD Pope, M Cunningham, AL TI Immunodeficiency virus uptake, turnover, and 2-phase transfer in human dendritic cells SO BLOOD LA English DT Article ID CD4(+) T-CELLS; CLASS-II TRANSPORT; C-TYPE LECTIN; DC-SIGN; LANGERHANS CELLS; ENVELOPE GLYCOPROTEIN; MANNOSE RECEPTOR; HIV-1 INFECTION; INTRAVAGINAL INOCULATION; PRODUCTIVE INFECTION AB HIV-1 subverts antigen processing in dendritic cells (DCs) resulting in viral uptake, infection, and transfer to T cells. Although DCs bound monomeric gp120 and HIV-1 similarly, virus rarely colocalized with endolysosomal markers, unlike gp120, suggesting HIV-1 alters endolysosomal trafficking. Virus within DC intracellular compartments rapidly moved to DCCD4(+) lymphocyte synapses when introduced to CD4(+) lymphocyte cultures. Although viral harboring and transfer from nonlysosomal compartments was transient, given DC-associated virus protein, nucleic acids, and infectious HIV-1 transfer to CD4(+), lymphocytes decayed within 24 hours. However a second long-term transfer phase was apparent in immature DCs after 48 hours as a zidovudine-sensitive rise in proviral DNA. Therefore, DCs transfer HIV-1 to CD4(+) lymphocytes in 2 distinct phases. Immature and mature DCs first divert virus from the endolysosomal pathway to the DC-T-cell synapse. Secondly, the later transfer phase from immature DCs is through de novo HIV-1 production. Thus, the controversy of DCs being infected or not infected for the mechanics of viral transfer to CD4(+) lymphocytes can be addressed as a function of time. (C) 2004 by The American Society of Hematology. C1 Westmead Millennium Inst, Ctr Virus Res, Westmead, NSW 2145, Australia. Populat Council, Ctr Biomed Res, New York, NY 10021 USA. Univ Melbourne, Dept Microbiol & Immunol, Parkville, Vic 3052, Australia. Univ Innsbruck, Dept Dermatol & Venerol, A-6020 Innsbruck, Austria. SAIC Frederick, Natl Canc Inst Frederick, AIDS Vaccice Program, Frederick, MD USA. RP Cunningham, AL (reprint author), Westmead Millennium Inst, Ctr Virus Res, POB 412,Darcy Rd, Westmead, NSW 2145, Australia. EM tony_cunningham@wmi.usyd.edu.au OI Cameron , Paul Urquhart/0000-0002-1906-6945; Cunningham, Anthony/0000-0002-6744-5667 FU NCI NIH HHS [N01-CO-124000]; NIAID NIH HHS [R21 AI52060, AI52048, R01 AI40877]; NICHD NIH HHS [P01 HD41752] NR 53 TC 269 Z9 277 U1 1 U2 14 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAR 15 PY 2004 VL 103 IS 6 BP 2170 EP 2179 DI 10.1182/blood-2003-09-3129 PG 10 WC Hematology SC Hematology GA 801VM UT WOS:000220123400035 PM 14630806 ER PT J AU Schiavoni, G Mattei, F Borghi, P Sestili, P Venditti, M Morse, HC Belardelli, F Gabriele, L AF Schiavoni, G Mattei, F Borghi, P Sestili, P Venditti, M Morse, HC Belardelli, F Gabriele, L TI ICSBP is critically involved in the normal development and trafficking of Langerhans cells and dermal dendritic cells SO BLOOD LA English DT Article ID SEQUENCE-BINDING-PROTEIN; COLONY-STIMULATING FACTOR; LYMPH-NODES; IN-VIVO; CONTACT HYPERSENSITIVITY; TRANSCRIPTION FACTOR; IMMUNE-RESPONSES; MYELOID CELLS; CUTTING EDGE; LIFE-SPAN AB Interferon consensus sequence-binding protein (ICSBP) is a transcription factor belonging to the interferon regulatory factor (IRF) family, recently shown to play a critical role in dendritic cell (DC) differentiation. Here, we analyzed the role of ICSBP in the development and trafficking of epidermal Langerhans cells (LCs) and dermal DCs and the implications for initiation of a competent immune response. ICSBP-/- mice exhibited a reduced frequency of LCs and a delayed mobility of DCs from skin that reflected a slower turnover rate in lymph nodes during steady-state conditions. Even under inflammatory changes, ICSBP-/- DCs displayed reduced mobility from skin to lymph nodes and, as a consequence, failed to induce a contact hypersensitivity (CHS) response, suggesting that these DCs were unable to initiate a competent antigen (Ag)-specific T-cell-mediated immunity. Moreover, bone marrow (BM)derived DCs from ICSBP-/- mice exhibited an immature phenotype and a severe reduction of interleukin 12 (IL-12) expression. These BM DCs also showed a marked defect in their migratory response to macrophage inflammatory protein 3alpha (MIP-3alpha), MIP-3beta, and the CC chemokine CCL21/6Ckine, which was paralleled by an impaired expression of the CC chemokine receptors, CCR6 and CCR7. Together, these results indicate that ICSBP is critically required for the development and trafficking of skin DCs, thus playing a critical role in the DC-mediated initiation of T-cell immunity. (C) 2004 by The American Society of Hematology. C1 Ist Super Sanita, Virol Lab, I-00161 Rome, Italy. NIAID, Immunopathol Lab, NIH, Bethesda, MD 20892 USA. RP Gabriele, L (reprint author), Ist Super Sanita, Virol Lab, Viale Regina Elena 299, I-00161 Rome, Italy. EM gabrilci@iss.it RI Mattei, Fabrizio/J-6585-2016; OI Mattei, Fabrizio/0000-0002-5357-7773; Morse, Herbert/0000-0002-9331-3705 NR 49 TC 77 Z9 78 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAR 15 PY 2004 VL 103 IS 6 BP 2221 EP 2228 DI 10.1182/blood-2003-09-3007 PG 8 WC Hematology SC Hematology GA 801VM UT WOS:000220123400041 PM 14615368 ER PT J AU Turcotte, K Gauthier, S Mitsos, LM Shustik, C Copeland, NG Jenkins, NA Fournet, JC Jolicoeur, P Gros, P AF Turcotte, K Gauthier, S Mitsos, LM Shustik, C Copeland, NG Jenkins, NA Fournet, JC Jolicoeur, P Gros, P TI Genetic control of myreloproliferation in BXH-2 mice SO BLOOD LA English DT Article ID MURINE LEUKEMIA VIRUSES; MYCOBACTERIUM-BOVIS BCG; QUANTITATIVE TRAIT LOCI; NATURAL-RESISTANCE; INTRACELLULAR INFECTIONS; MOUSE STRAINS; MAJOR DETERMINANT; FLANKING MARKERS; NRAMP1; SUSCEPTIBILITY AB While studying the unique Nramp1 (Slc11a1)-independent susceptibility to Mycobacterium bovis (BCG) infection of BXH-2 mice, we noted that these mice develop important splenomegaly and enlargement of lymph nodes. Segregation analyses in several F2 crosses showed that splenomegaly segregates as a single recessive trait caused by a novel mutation in BXH-2, independent of the infection. Histologic and fluorescence-activated cell sorter (FACS) analyses indicated that splenomegaly is associated with a large increase in Mac1(+)/GR1(+) (macrophage antigen-1(+)/granulocyte differentiation antigen 1(+)) granulocyte precursors in spleen, lymph nodes, and bone marrow, resembling a myeloproliferative syndrome. This is concomitant to extramedullary erythropoiesis in the spleen, as measured by proportion of Ter119(+) erythroid cells. The locus controlling this myeloproliferative syndrome and splenomegaly was designated Myls and maps to an 18 centimorgan (M) region of chromosome 8, which also contains an integrated copy of an N-ecotropic murine leukemia virus (MuLV) provirus (Emv2). The relationship between Myls, expansion of Mac1(+)/GR1(+) cells, and Emv2 was investigated. Homozygosity at Myls is necessary but not sufficient for Becotropic virus replication in splenocytes, the extent of which appears to be under separate genetic control. Our results suggest a model in which Myls-dependent myeloproliferation in BXH-2 acts as a predisposing factor for the subsequent development of virally induced myeloid leukemia characteristic of this strain. (C) 2004 by The American Society of Hematology. C1 McGill Univ, Dept Biochem, Montreal, PQ H3G 1Y6, Canada. Royal Victoria Hosp, Dept Hematol, Montreal, PQ H3A 1A1, Canada. NCI, Mouse Canc Genet Program, Frederick, MD 21701 USA. Hop Ste Justine, Dept Pathol, Montreal, PQ, Canada. Clin Res Inst Montreal, Dept Biol Mol, Montreal, PQ H2W 1R7, Canada. McGill Univ, Dept Expt Med, Montreal, PQ, Canada. Univ Montreal, Dept Microbiol & Immunol, Montreal, PQ H3C 3J7, Canada. RP Gros, P (reprint author), McGill Univ, Dept Biochem, 3655 Promenade Sir William Osler,Room 907, Montreal, PQ H3G 1Y6, Canada. EM philippe.gros@mcgill.ca NR 29 TC 24 Z9 24 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAR 15 PY 2004 VL 103 IS 6 BP 2343 EP 2350 DI 10.1182/blood-06-1852 PG 8 WC Hematology SC Hematology GA 801VM UT WOS:000220123400056 PM 14630819 ER PT J AU Ilbanez, V Pietrini, P Furey, ML Alexander, GE Millet, P Bokde, ALW Teichberg, D Schapiro, MB Horwitz, B Rapoport, SI AF Ilbanez, V Pietrini, P Furey, ML Alexander, GE Millet, P Bokde, ALW Teichberg, D Schapiro, MB Horwitz, B Rapoport, SI TI Resting state brain glucose metabolism is not reduced in normotensive healthy men during aging, after correction for brain atrophy SO BRAIN RESEARCH BULLETIN LA English DT Article DE aging; glucose; positron; atrophy; human; brain; tomography ID POSITRON EMISSION TOMOGRAPHY; AGE-RELATED DIFFERENCES; HUMAN CEREBRAL METABOLISM; ALZHEIMERS-DISEASE; BLOOD-FLOW; PET; DEMENTIA; VOLUME; PATTERNS; GENDER AB Studies using positron emission tomography (PET) have reported that global and regional values for cerebral blood flow and metabolic rates for glucose (CMRglc and rCMRglc) decline with age in humans. We wished to determine if such decreases could have reflected a partial volume effect (PVE) of cerebral atrophy in the elderly, rather than "intrinsic" reductions per gram brain. We used PET to compare rCMRglc, before and after correcting for the PVE, between 13 healthy older men (aged: 55-82 years) and 11 healthy young men (aged: 22-34 years). PET was performed with F-18-fluoro-2-deoxy-D-glucose while the subjects were in the "resting" state (eyes covered and ears plugged with cotton). The PET scans were normalized to a common brain volume after superimposing them on the subjects' tissue segmented magnetic resonance scans. Analysis showed that rCMRglc in the absence of a PVE correction was significantly less in the older group in insular, frontal, superior temporal cortical. and thalamic regions. Statistical significant differences in rCMRglc, however, were absent after the PVE correction. Thus. statistically significant age reductions in regional brain glucose metabolism, corrected for brain atrophy, are not detectable in healthy normotensive men scanned while in the resting state. (C) 2004 Elsevier Inc. All rights reserved. C1 NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. Neuroimaging Unit, Div Neuropsychiat, Geneva, Switzerland. Univ Pisa, Dept Expt Pathol, Pisa, Italy. Arizona State Univ, Dept Psychol, Arizona Alzheimers Dis Res Ctr, Tempe, AZ USA. Univ Munich, Dept Psychiat, D-8000 Munich, Germany. Cincinnati Childrens Hosp, Med Ctr, Dept Pediat Neurol, Cincinnati, OH USA. NIDCD, Brain Imaging & Modeling Sect, NIH, Bethesda, MD USA. RP Rapoport, SI (reprint author), NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. EM sir@helix.nih.gov RI Millet, Philippe/A-3790-2013; Furey, Maura/H-5273-2013 NR 53 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 0361-9230 J9 BRAIN RES BULL JI Brain Res. Bull. PD MAR 15 PY 2004 VL 63 IS 2 BP 147 EP 154 DI 10.1016/j.brainresbull.2004.02.003 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 822JF UT WOS:000221534600009 ER PT J AU Wang, M Devereux, TR Vikis, HG McCulloch, SD Holliday, W Anna, C Wang, Y Bebenek, K Kunkel, TA Guan, KL You, M AF Wang, M Devereux, TR Vikis, HG McCulloch, SD Holliday, W Anna, C Wang, Y Bebenek, K Kunkel, TA Guan, KL You, M TI Pol iota is a candidate for the mouse pulmonary adenoma resistance 2 locus, a major modifier of chemically induced lung neoplasia SO CANCER RESEARCH LA English DT Article ID DNA-POLYMERASE-IOTA; TUMOR-SUPPRESSOR LOCUS; CHROMOSOME 18Q21; SOMATIC HYPERMUTATION; REPLICATION MACHINERY; URETHANE-INDUCTION; BALB/CBYJ MICE; PAR2 LOCUS; IN-VITRO; CANCER AB this study, we performed systematic candidate gene analyses of the Pulmonary adenoma resistance 2 locus. Differential gene expression in lung tissues and nucleotide polymorphisms in coding regions between A/J and BALB/cJ mice were examined using reverse transcription-PCR and direct sequencing. Although not all genes in the interval were analyzed at this moment due to the recent database updating, we have found that the Pol iota gene, encoding the DNA polymerase iota, contains 25 nucleotide polymorphisms in its coding region between A/J and BALB/cJ mice, resulting in a total of ten amino acid changes. Primer extension assays with purified BALB/cJ and A/J proteins in vitro demonstrate that both forms of Pol iota are active but that they may differ in substrate discrimination, which may affect the formation of Kras2 mutations in mouse lung tumors. Altered expression of POL iota protein and an amino acid-changing nucleotide polymorphism were observed in human lung cancer cells, suggesting a possible role in the development of lung cancer. Thus, our data support the Pol iota gene as a modifier of lung tumorigenesis by altering DNA polymerase activity. C1 Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA. Washington Univ, Sch Med, Alvin J Siteman Canc Ctr, St Louis, MO 63110 USA. NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC USA. NIEHS, Genet Mol Lab, NIH, Res Triangle Pk, NC USA. NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC USA. Univ Michigan, Dept Biol Chem, Ann Arbor, MI 48109 USA. RP You, M (reprint author), Washington Univ, Sch Med, Dept Surg, 660 S Euclid Ave, St Louis, MO 63110 USA. EM youm@msnotes.wustl.edu FU NCI NIH HHS [R01 CA 58554, R01 CA 099147] NR 40 TC 41 Z9 50 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAR 15 PY 2004 VL 64 IS 6 BP 1924 EP 1931 DI 10.1158/0008-5472.CAN-03-3080 PG 8 WC Oncology SC Oncology GA 803RV UT WOS:000220249100007 PM 15026325 ER PT J AU Cheung, AMY Elia, A Tsao, MS Done, S Wagner, KU Hennighausen, L Hakem, R Mak, TW AF Cheung, AMY Elia, A Tsao, MS Done, S Wagner, KU Hennighausen, L Hakem, R Mak, TW TI Brca2 deficiency does not impair mammary epithelium development but promotes mammary adenocarcinoma formation in p53(+/-) mutant mice SO CANCER RESEARCH LA English DT Article ID CANCER SUSCEPTIBILITY GENE; GERM-LINE MUTATIONS; BREAST-CANCER; OVARIAN-CANCER; DNA-REPAIR; P53; RECOMBINATION; EXPRESSION; GLAND; CHROMOSOME AB Brca2 is an important tumor suppressor associated with susceptibility to breast cancer. Although increasing evidence indicates that the primary function of Brca2 is to facilitate the repair of DNA damage via the homologous recombination pathway, how Brca2 prevents breast cancer is largely unknown. To study the role of Brca2 specifically in mammary epithelium development, we crossed mice bearing the conditionally deficient allele Brca2(flox9-10) to mouse mammary tumor virus- or whey acidic protein-Cre transgenic lines. Analysis of these animals showed that Brca2 is not required for epithelial expansion in mammary glands of pregnant mice. In addition, examination of mammary gland involution revealed normal kinetics of mammary alveolar cell apoptosis after weaning of litters. Nevertheless, Brca2-deficient mice developed mammary adenocarcinomas after a long latency (average, 1.6 years). Detailed histopathological analysis of four of these tumors demonstrated that three of them showed abnormal p53 protein expression. A mutation in the p53 gene was detected in one case. Moreover, homozygosity versus heterozygosity for the Brca2 mutation heavily skewed the tumor spectrum toward mammary adenocarcinoma development in p53(+/-) mice. Our data indicate that Brca2 is not essential for mammary epithelium development but that Brca2 deficiency and down-regulated p53 expression can work jointly to promote mammary tumorigenesis. C1 Univ Hlth Network, Adv Med Discovery Inst, Toronto, ON M5G 2C1, Canada. Univ Toronto, Ontario Canc Inst, Toronto, ON, Canada. Univ Toronto, Dept Med Biophys, Toronto, ON, Canada. Univ Nebraska, Med Ctr, Eppley Inst Res Canc & Allied Dis, Omaha, NE 68182 USA. NIDDKD, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA. RP Mak, TW (reprint author), Univ Hlth Network, Adv Med Discovery Inst, 620 Univ Ave,Suite 706, Toronto, ON M5G 2C1, Canada. EM tmak@uhnres.utoronto.ca RI Wagner, Kay-Uwe/B-6044-2009; OI Done, Susan/0000-0002-1770-988X NR 38 TC 24 Z9 24 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAR 15 PY 2004 VL 64 IS 6 BP 1959 EP 1965 DI 10.1158/0008-5472.CAN-03-2270 PG 7 WC Oncology SC Oncology GA 803RV UT WOS:000220249100012 PM 15026330 ER PT J AU Shappell, SB Thomas, GV Roberts, RL Herbert, R Ittmann, MM Rubin, MA Humphrey, PA Sundberg, JP Rozengurt, N Barrios, R Ward, JM Cardiff, RD AF Shappell, SB Thomas, GV Roberts, RL Herbert, R Ittmann, MM Rubin, MA Humphrey, PA Sundberg, JP Rozengurt, N Barrios, R Ward, JM Cardiff, RD TI Prostate pathology of genetically engineered mice: Definitions and classification. The consensus report from the bar harbor meeting of the mouse models of human cancer consortium prostate pathology committee SO CANCER RESEARCH LA English DT Review ID LARGE T-ANTIGEN; PROLIFERATIVE INFLAMMATORY ATROPHY; NEEDLE-BIOPSY SPECIMENS; ACCESSORY SEX-ORGANS; INTRAEPITHELIAL NEOPLASIA; TRANSGENIC MICE; RADICAL PROSTATECTOMY; POSTATROPHIC HYPERPLASIA; PERINEURAL INVASION; TRANSITION ZONE AB The Pathological Classification of Prostate Lesions in Genetically Engineered Mice (GEM) is the result of a directive from the National Cancer Institute Mouse Models of Human Cancer Consortium Prostate Steering Committee to provide a hierarchical taxonomy of disorders of the mouse prostate to facilitate classification of existing and newly created mouse models and the translation to human prostate pathology. The proposed Bar Harbor Classification system is the culmination of three meetings and workshops attended by various members of the Prostate Pathology Committee of the Mouse Models of Human Cancer Consortium. A 2-day Pathology Workshop was held at The Jackson Laboratory in Bar Harbor, Maine, in October 2001, in which study sets of 93 slides from 22 GEM models were provided to individual panel members. The comparison of mouse and human prostate anatomy and disease demonstrates significant differences and considerable similarities that bear on the interpretation of the origin and natural history of their diseases. The recommended classification of mouse prostate pathology is hierarchical, and includes developmental, inflammatory, benign proliferative, and neoplastic disorders. Among the neoplastic disorders, preinvasive, microinvasive, and poorly differentiated neoplasms received the most attention. Specific criteria were recommended and will be discussed. Transitions between neoplastic states were of particular concern. Preinvasive neoplasias of the mouse prostate were recognized as focal, atypical, and progressive lesions. These lesions were designated as mouse prostatic intraepithelial neoplasia (mPIN). Some atypical lesions were identified in mouse models without evidence of progression to malignancy. The panel recommended that mPIN lesions not be given histological grades, but that mPIN be further classified as to the absence or presence of documented associated progression to invasive carcinoma. Criteria for recognizing microinvasion, for classification of invasive gland-forming adenocarcinomas, and for characterizing poorly differentiated tumors, including neuroendocrine carcinomas, were developed and are discussed. The uniform application of defined terminology is essential for correlating results between different laboratories and models. It is recommended that investigators use the Bar Harbor Classification system when characterizing new GEM models or when conducting experimental interventions that may alter the phenotype or natural history of lesion progression in existing models. C1 Univ Calif Davis, Ctr Comparat Med, Davis, CA 95616 USA. NCI, Vet & Tumor Pathol Sect, Off Lab Anim Resources, Frederick, MD 21701 USA. Jackson Lab, Bar Harbor, ME 04609 USA. Washington Univ, Dept Pathol, St Louis, MO 63130 USA. Washington Univ, Dept Urol, St Louis, MO 63130 USA. Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Urol, Boston, MA 02115 USA. Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. Univ Calif Los Angeles, Dept Pathol, Los Angeles, CA 90024 USA. Vanderbilt Univ, Med Ctr, Dept Urol Surg, Nashville, TN USA. Vanderbilt Univ, Med Ctr, Vanderbilt Ingram Canc Ctr, Nashville, TN USA. Vanderbilt Univ, Med Ctr, Vanderbilt Prostate Canc Ctr, Nashville, TN USA. Vanderbilt Univ, Med Ctr, Dept Pathol, Nashville, TN USA. RP Shappell, SB (reprint author), Oppenheimer Urol Reference Lab, 1854 Airlane Dr,Suite 17A, Nashville, TN 37210 USA. EM scottshappell@ourlab.net OI Rubin, Mark/0000-0002-8321-9950 FU NCI NIH HHS [U01 CA 98013] NR 106 TC 349 Z9 356 U1 2 U2 15 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAR 15 PY 2004 VL 64 IS 6 BP 2270 EP 2305 DI 10.1158/0008-5472.CAN-03-0946 PG 36 WC Oncology SC Oncology GA 803RV UT WOS:000220249100055 PM 15026373 ER PT J AU Tsang, KY Palena, C Gulley, J Arlen, P Schlom, J AF Tsang, KY Palena, C Gulley, J Arlen, P Schlom, J TI A human cytotoxic T-lymphocyte epitope and its agonist epitope from the nonvariable number of tandem repeat sequence of MUC-1 SO CLINICAL CANCER RESEARCH LA English DT Article ID POLYMORPHIC EPITHELIAL MUCIN; HUMAN CARCINOEMBRYONIC ANTIGEN; DENDRITIC CELLS; BREAST-CANCER; IN-VIVO; PHASE-I; PEPTIDE; EXPRESSION; VIRUS; IDENTIFICATION AB Purpose: MUC-1/DF-3 remains an attractive target for vaccine therapy. It is overexpressed in the majority of human carcinomas and multiple myeloma. Clinical trials using MUC-1-based vaccines have demonstrated safety, clinical responses, and the induction of T-cell responses directed against MUC-1. Previous studies in experimental models and in clinical trials have demonstrated that altering the amino acid sequence of a "self" epitope can lead to the generation of an enhancer agonist epitope capable of eliciting stronger T-cell responses than the native epitope can. Experimental Design and Results: We describe here the identification of six novel class I HLA-A2 epitopes of MUC-1 that reside outside of the variable number of tandem repeat region. Each is shown to have the ability to activate human T cells as measured by IFN-gamma production. One epitope (ATWGQDVTSV, at amino acid position 92-101 and designated P-92), which demonstrated the highest level of binding to HLA-A2 and which induced the highest level of IFN-gamma in human T cells, was further studied for the generation of potential enhancer agonist epitopes. Of four potential agonists identified, one epitope (A (L) under bar WGQDVTSV, designated P-93L) was identified as an enhancer agonist. Compared with the native P-92 peptide, the P-93L agonist (a) bound HLA-A2 at lower peptide concentrations, (b) demonstrated a higher avidity for HLA-A2 in dissociation assays, (c) when used with antigen-presenting cells, induced the production of more IFN-gamma by T cells than with the use of the native peptide, and (d) was capable of more efficiently generating MUC-1-specific human T-cell lines from normal volunteers and pancreatic cancer patients. Most importantly, the T-cell lines generated using the agonist epitope were more efficient than those generated with the native epitope in the lysis of targets pulsed with the native epitope and in the lysis of HLA-A2 human tumor cells expressing MUC-1. Conclusions: In addition to the identification of novel MUC-1 epitopes outside the variable number of tandem repeat region, the studies reported here describe the first agonist epitope of MUC-1. The employment of this agonist epitope in peptide-, protein-, and vector-based vaccines may well aid in the development of effective vaccines for a range of human cancers. C1 NCI, Tumor Immunol & Biol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Schlom, J (reprint author), NCI, Tumor Immunol & Biol Lab, Canc Res Ctr, NIH, 10 Ctr Dr,Room 8B09,MSC 1750, Bethesda, MD 20892 USA. EM js141c@nih.gov RI Gulley, James/K-4139-2016 OI Gulley, James/0000-0002-6569-2912 NR 60 TC 47 Z9 47 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAR 15 PY 2004 VL 10 IS 6 BP 2139 EP 2149 DI 10.1158/1078-0432.CCR-1011-03 PG 11 WC Oncology SC Oncology GA 804ZW UT WOS:000220337600036 PM 15041735 ER PT J AU Hotez, PJ Remme, JHF Buss, P Alleyne, G Morel, C Breman, JG AF Hotez, PJ Remme, JHF Buss, P Alleyne, G Morel, C Breman, JG TI Combating tropical infectious diseases: Report of the disease control priorities in developing countries project SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material ID LYMPHATIC FILARIASIS; COST-EFFECTIVENESS; DIARRHEAL DISEASE; GLOBAL BURDEN; MALARIA; SCHISTOSOMIASIS; LEISHMANIASIS; TUBERCULOSIS; ELIMINATION; CHALLENGES AB Infectious diseases are responsible for >25% of the global disease toll. The new Disease Control Priorities in Developing Countries Project (DCPP) aims to decrease the burden of these diseases by producing science-based analyses from demographic, epidemiologic, disease intervention, and economic evidence for the purpose of defining disease priorities and implementing control measures. The DCPP recently reviewed selected tropical infectious diseases, examined successful control experiences, and defined unsettled patient treatment, prevention, and research issues. Disease elimination programs against American trypanosomiasis ( Chagas disease), onchocerciasis, lymphatic filariasis, leprosy, trachoma, and measles are succeeding. Dengue, leishmaniasis, African trypanosomiasis, malaria, diarrheal diseases, helminthic infections, and tuberculosis have reemerged because of inadequate interventions and control strategies and the breakdown of health delivery systems. Application of technologies must be cost-effective and intensified research is essential if these and other scourges are to be controlled or eliminated in the 21st century. C1 NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. George Washington Univ, Washington, DC USA. Pan Amer Hlth Org, Washington, DC USA. WHO, CH-1211 Geneva, Switzerland. Fdn Oswaldo Cruz, Rio De Janeiro, Brazil. RP Breman, JG (reprint author), NIH, Fogarty Int Ctr, Bldg 16,Rm 214,16 Ctr Dr,MSC 6705, Bethesda, MD 20892 USA. EM jbreman@nih.gov RI Morel, Carlos/B-4079-2009; OI Hotez, Peter/0000-0001-8770-1042 NR 43 TC 77 Z9 79 U1 1 U2 14 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD MAR 15 PY 2004 VL 38 IS 6 BP 871 EP 878 DI 10.1086/382077 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 800QI UT WOS:000220042400023 PM 14999633 ER PT J AU Keusch, GT AF Keusch, GT TI Global health, personal action SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material C1 NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Keusch, GT (reprint author), Boston Univ Med Campus,715 Albany St,T443W, Boston, MA 02118 USA. EM keuschg@nih.gov NR 5 TC 0 Z9 0 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD MAR 15 PY 2004 VL 38 IS 6 BP 879 EP 880 DI 10.1086/382085 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 800QI UT WOS:000220042400024 PM 14999634 ER PT J AU Bray, M Buller, M AF Bray, M Buller, M TI Looking back at smallpox SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID COWPOX VIRUS CHALLENGE; VACCINIA VIRUS; HAEMORRHAGIC SMALLPOX; VARIOLA VIRUS; PROTECTS MICE; VACCINATION; CIDOFOVIR; INFECTION; COMPLICATIONS; MANAGEMENT AB Smallpox apparently arose through transfer of variola virus to humans from another animal species. By causing a brief infection that required close contact for transmission and engendered solid immunity, the agent was always vulnerable to simple isolation measures. The high replicative fidelity of the viral DNA polymerase limited variola's ability to adapt to humans and preserved orthopoxviral antigenic cross-reactivity, so that vaccinia vaccination protected against smallpox. Host-derived genes encoding immunomodulatory proteins helped shelter viral replication from innate immune responses. Examination of clinical variants suggests that severity of illness was usually determined by host responses during the incubation period. Control of viral replication was aided by early postexposure vaccination and might be strengthened by additional immunological interventions. Massive inflammatory responses were responsible for major features of illness. Some patients with high levels of circulating virus developed hemorrhagic disease resembling septic shock. Continued study of virus-host interactions is needed to defend against genetically modified agents. C1 NIAID, Biodefense Clin Res Branch, OCR OD, NIH, Bethesda, MD 20892 USA. St Louis Univ, Dept Mol Microbiol & Immunol, St Louis, MO 63103 USA. RP Bray, M (reprint author), NIAID, Biodefense Clin Res Branch, OCR OD, NIH, Bethesda, MD 20892 USA. EM mbray@niaid.nih.gov NR 36 TC 36 Z9 38 U1 1 U2 4 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD MAR 15 PY 2004 VL 38 IS 6 BP 882 EP 889 DI 10.1086/381976 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 800QI UT WOS:000220042400026 PM 14999635 ER PT J AU Palella, FJ Cole, SR Chmiel, JS Riddler, SA Visscher, B Dobs, A Williams, C AF Palella, FJ Cole, SR Chmiel, JS Riddler, SA Visscher, B Dobs, A Williams, C TI Anthropometrics and examiner-reported body habitus abnormalities in the Multicenter AIDS Cohort Study SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID HIV-INFECTION; LIPODYSTROPHY; INHIBITOR; THERAPY; VIRUS; MEN AB We undertook anthropometric assessments of 530 HIV-seropositive and 314 HIV-seronegative men in the Multicenter AIDS Cohort Study at a regular visit that occurred between 1 April and 30 September 1999. We found anthropomorphic differences that were independent of age: the 384 seropositive men receiving HAART had diminished body size and higher frequency and severity of body habitus abnormalities, particularly lipoatrophy, compared with the 314 seronegative men. C1 Northwestern Univ, Feinberg Sch Med, Div Infect Dis, Chicago, IL 60611 USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. NIAID, NIH, Rockville, MD USA. Johns Hopkins Univ, Baltimore, MD USA. RP Palella, FJ (reprint author), Northwestern Univ, Feinberg Sch Med, Div Infect Dis, 676 N St Clair,Ste 200, Chicago, IL 60611 USA. EM f-palella@northwestern.edu FU NCRR NIH HHS [5-M01-RR-00722]; NIAID NIH HHS [U01-AI-35043, U01-AI-37984, U01-AI-37613, U01-AI-35042, U01-AI-35040, U01-AI-35039, U01-AI-35041] NR 14 TC 35 Z9 36 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD MAR 15 PY 2004 VL 38 IS 6 BP 903 EP 907 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 800QI UT WOS:000220042400029 PM 14999638 ER PT J AU Zhou, YH Chen, ZC AF Zhou, YH Chen, ZC TI Is the immune system impaired in patients with severe acute respiratory syndrome? SO CLINICAL INFECTIOUS DISEASES LA English DT Letter ID SARS; CORONAVIRUS C1 NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Zhou, YH (reprint author), NIAID, Infect Dis Lab, NIH, Bldg 50,Rm 6535,50 S Dr,MSC-8009, Bethesda, MD 20892 USA. EM yzhou@niaid.nih.gov NR 10 TC 2 Z9 4 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD MAR 15 PY 2004 VL 38 IS 6 BP 921 EP 922 DI 10.1086/382081 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 800QI UT WOS:000220042400033 PM 14999642 ER PT J AU Bry, C Maass, K Miyoshi, K Willecke, K Ott, T Robinson, GW Hennighausen, L AF Bry, C Maass, K Miyoshi, K Willecke, K Ott, T Robinson, GW Hennighausen, L TI Loss of connexin 26 in mammary epithelium during early but not during late pregnancy results in unscheduled apoptosis and impaired development SO DEVELOPMENTAL BIOLOGY LA English DT Article DE connexins; gap junction; mammary gland; apoptosis; alveolar development; differentiation ID GROWTH-FACTOR-ALPHA; BCL-X GENE; TRANSGENIC MICE; HUMAN BREAST; CONDITIONAL DELETION; MOUSE; CELLS; EXPRESSION; GLAND; DIFFERENTIATION AB Gap junctions are intercellular channels that are formed by the protein family of connexins (Cxs). In mammary tissue, Cx26 and Cx32 are present in the secretory epithelium and Cx43 is localized in the myoepithelium. The expression of Cx26 and Cx32 is induced during pregnancy and lactation, respectively, thus suggesting unique roles for them in the functional development of the gland. The requirement for these connexins was explored using several strains of genetically altered mice: mice with an inactivated Cx32 gene, mice in which the Cx43 gene had been replaced with the Cx32 gene (Cx43KI32 mice) and mice in which the Cx26 gene was specifically ablated in mammary epithelium at different stages of development using Cre-loxP-based recombination. Normal mammary development was obtained in Cx32-null mice and in Cx43KI32 mammary tissue. In contrast, loss of Cx26 in mammary epithelium before puberty resulted in abrogated lobulo-alveolar development and increased cell death during pregnancy, which was accompanied by impaired lactation. Loss of Cx26 in mammary epithelium during the later part of pregnancy did not adversely interfere with functional mammary development. These results demonstrate that the presence of Cx26 is critical during early stages but not during the end of pregnancy when the tissue has completed functional differentiation. Cx26 is considered a tumor suppressor gene and Cx26-null mammary tissue was evaluated after five pregnancies. No hyperproliferation or hyperplasia was observed, suggesting that Cx26 does not function as a tumor suppressor. Published by Elsevier Inc. C1 NIDDKD, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA. Univ Bonn, Inst Genet, D-5300 Bonn, Germany. Univ Tokushima, Sch Dent, Dept Biochem, Tokushima 7708504, Japan. RP Hennighausen, L (reprint author), NIDDKD, Lab Genet & Physiol, NIH, 9000 Rockville Pike,Bldg 8,Room 101, Bethesda, MD 20892 USA. EM hennighausen@nih.gov RI Robinson, Gertraud/I-2136-2012; OI Maass, Karen/0000-0001-9815-841X NR 36 TC 34 Z9 34 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD MAR 15 PY 2004 VL 267 IS 2 BP 418 EP 429 DI 10.1016/j.ydbio.2003.11.022 PG 12 WC Developmental Biology SC Developmental Biology GA 805FE UT WOS:000220351400011 PM 15013803 ER PT J AU Gladwin, MT Crawford, JH Patel, RP AF Gladwin, MT Crawford, JH Patel, RP TI The biochemistry of nitric oxide, nitrite, and hemoglobin: Role in blood flow regulation SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Review DE nitrite; hemoglobin; vasodilation; blood flow; oxygen sensing; S-nitroso-hemoglobin; iron-nitrosyl-hemoglobin; free radicals ID ENDOTHELIUM-DEPENDENT RELAXATION; SICKLE-CELL-DISEASE; SMOOTH-MUSCLE RELAXATION; S-NITROSOHEMOGLOBIN; PULMONARY-HYPERTENSION; RELAXING FACTOR; SODIUM-NITRITE; HUMAN-PLASMA; L-ARGININE; SYSTEMIC VASOCONSTRICTION AB Nitric oxide (NO) plays a fundamental role in maintaining normal vasomotor tone. Recent data implicate a critical function for hemoglobin and the erythrocyte in regulating the activity of NO in the vascular compartment. Intravascular hemolysis releases hemoglobin from the red blood cell into plasma (cell-free plasma hemoglobin), which is then able to scavenge endothelium-derived NO 600-fold faster than erythrocytic hemoglobin, thereby disrupting NO homeostasis. This may lead to vasoconstriction, decreased blood flow, platelet activation, increased endothelin-1 expression (ET-1), and end-organ injury, thus suggesting a novel mechanism of disease for hereditary and acquired hemolytic conditions such as sickle cell disease and cardiopulmonary bypass. Furthermore, therapy with NO gas inhalation or infusion of sodium nitrite during hemolysis may attenuate this disruption in vasomotor balance by oxidizing plasma cell-free hemoglobin, thereby preventing the consumption of endogenous NO and the associated pathophysiological changes. In addition to providing an NO scavenging role in the physiological regulation of NO-dependent vasodilation, hemoglobin and the erythrocyte may deliver NO as the hemoglobin deoxygenates. While this process has previously been ascribed to S-nitrosated hemoglobin, recent data from our laboratories suggest that deoxygenated hemoglobin reduces nitrite to NO and vasodilates the human circulation along the physiological oxygen gradient. This newly described role of hemoglobin as a nitrite reductase is discussed in the context of blood flow regulation, oxygen sensing, and nitrite-based therapeutics. (C) 2004 Elsevier Inc. All rights reserved. C1 NIDDKD, NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. NIDDKD, NIH, Biol Chem Lab, Bethesda, MD 20892 USA. Univ Alabama, Dept Pathol, Birmingham, AL USA. Univ Alabama, Ctr Free Radical Biol, Birmingham, AL USA. RP Gladwin, MT (reprint author), NIDDKD, NIH, Dept Crit Care Med, Ctr Clin, Bldg 10,Room 7D-43,10 ctr Dr, Bethesda, MD 20892 USA. EM mgladwin@nih.gov; patel@path.uab.edu OI Patel, Rakesh/0000-0002-1526-4303 FU NHLBI NIH HHS [HL70146] NR 87 TC 226 Z9 238 U1 2 U2 22 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. PD MAR 15 PY 2004 VL 36 IS 6 BP 707 EP 717 DI 10.1016/freeradbiomed.2003.11.032 PG 11 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 803PV UT WOS:000220243900003 PM 14990351 ER PT J AU Raychowdhury, MK Gonzalez-Perrett, S Timpanaro, GA Chasan, B Goldmann, WH Stahl, S Cooney, A Goldin, E Cantiello, HF AF Raychowdhury, MK Gonzalez-Perrett, S Timpanaro, GA Chasan, B Goldmann, WH Stahl, S Cooney, A Goldin, E Cantiello, HF TI Molecular pathophysiology of mucolipidosis type IV: pH dysregulation of the mucolipin-1 cation channel SO HUMAN MOLECULAR GENETICS LA English DT Article ID CAENORHABDITIS-ELEGANS; ABNORMAL TRANSPORT; VESICLE TRANSPORT; LYSOSOMAL PATHWAY; MEMBRANE-PROTEIN; POTENTIAL ROLE; K+ CHANNELS; POLYCYSTIN-2; CELLS; GENE AB Mucolipidosis type IV (MLIV) is an autosomal recessive neurogenetic disorder characterized by developmental abnormalities of the brain and impaired neurological, ophthalmologic and gastric function. Large vacuoles accumulate in various types of cells in MLIV patients. However, the pathophysiology of the disease at the cellular level is still unknown. MLIV is caused by mutations in a recently described gene, MCOLN1, encoding mucolipin-1 (ML1), a 65 kDa protein whose function is also unknown. ML1 shows sequence homology and topological similarities with polycystin-2 and other transient receptor potential (Trp) channels. In this study, we assessed both, whether ML1 has ion channel properties, and whether disease-causing mutations in MCOLN1 have functional differences with the wild-type (WT) protein. ML1 channel function was assessed from endosomal vesicles of null (MCOLN1(-/-)) and ML1 over-expressing cells, and liposomes containing the in vitro translated protein. Evidence from both preparations indicated that WT ML1 is a multiple subconductance non-selective cation channel whose function is inhibited by a reduction of pH. The V446L and DeltaF408 MLIV causing mutations retain channel function but not the sharp inhibition by lowering pH. Atomic force imaging of ML1 channels indicated that changes in pH modified the aggregation of unitary channels. Mutant-ML1 did not change in size on reduction of pH. The data indicate that ML1 channel activity is regulated by a pH-dependent mechanism that is deficient in some MLIV causing mutations of the gene. The evidence also supports a novel role for cation channels in the acidification and normal endosomal function. C1 Massachusetts Gen Hosp E, Renal Unit, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Univ Buenos Aires, Fac Farm & Bioquim, Dept Fisicoquim & Quim Analit, Lab Canales Ionicos, RA-1113 Buenos Aires, DF, Argentina. Univ Buenos Aires, Fac Med, Dept Fisiol, RA-1425 Buenos Aires, DF, Argentina. Boston Univ, Dept Phys, Boston, MA 02215 USA. NIH, Dev & Metab Neurol Branch, Bethesda, MD 20892 USA. RP Cantiello, HF (reprint author), Massachusetts Gen Hosp E, Renal Unit, 149 13th St, Charlestown, MA 02129 USA. EM cantiello@helix.mgh.harvard.edu RI Goldmann, Wolfgang/H-5572-2013; OI Montalbetti, Nicolas/0000-0003-2897-9540 FU NIDDK NIH HHS [T32DK07540C15] NR 58 TC 84 Z9 87 U1 0 U2 2 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 MAR 15 PY 2004 VL 13 IS 6 BP 617 EP 627 DI 10.1093/hmg/ddh067 PG 11 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 801CK UT WOS:000220073800005 PM 14749347 ER PT J AU Li, LY Wartchow, CA Danthi, SN Shen, ZM Dechene, N Pease, J Choi, HS Doede, T Chu, P Ning, SC Lee, DY Bednarski, MD Knox, SJ AF Li, LY Wartchow, CA Danthi, SN Shen, ZM Dechene, N Pease, J Choi, HS Doede, T Chu, P Ning, SC Lee, DY Bednarski, MD Knox, SJ TI A novel antiangiogenesis therapy using an integrin antagonist or anti-FLK-1 antibody coated Y-90-labeled nanoparticles SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE radiotherapy; nanoparticle; integrin; Flk-1 ID ENDOTHELIAL GROWTH-FACTOR; ANGIOGENESIS IN-VIVO; TUMOR ANGIOGENESIS; RANDOMIZED-TRIAL; FACTOR RECEPTOR; BLOOD-VESSELS; HUMAN SKIN; ALPHA(V)BETA(3); CANCER; EXPRESSION AB Purpose: Integrin alpha(v)beta(3) and vascular endothelial growth factor receptor 2 (Flk-1) have been shown to be involved in tumor-induced angiogenesis. Selective targeting of upregulated alpha(v)beta(3) and Flk-1 on the neovasculature of tumors is a novel antiangiogenesis strategy for treating a wide variety of solid tumors. In the studies described here, we investigated the potential therapeutic efficacy of two three-component treatment regimens using two murine tumor models. Methods and Materials: The treatment regimens used nanoparticle (NP) based targeting agents radiolabeled with Y-90. The small molecule integrin antagonist (IA) 4-[2-(3,4,5,6-tetrahydropyrimidin-2-ylamino)ethoxy]benzoyl-2-(5)-aminoethylsulfonylamino-beta-alanine, which binds to the integrin a,,03, and a monoclonal antibody against murine Flk-1 (anti-Flk-1 MAb) were used to target the NPs. Murine tumor models K1735-M2 (melanoma) and CT-26 (colon adenocarcinoma) were used to evaluate the treatment efficacy. Results: In K1735-M2- and CT-26 tumors, a single treatment with IA-NP-Y-90 (14.2 mug/g IA, 5 or 6 muCi/g Y-90) caused a significant tumor growth delay compared to untreated control tumors, as well as tumors treated with IA, IA-NP, and NP-Y-90, respectively (p < 0.025, Wilcoxon test). In K1735-M2 tumors, a single treatment with anti-Flk-1 MAb-NP-Y-90 (0.36 μg/g anti-Flk-1 MAb, 5 μCi/g Y-90) also caused a significant tumor growth delay (p < 0.05, Wilcoxon test) compared to untreated tumors, as well as tumors treated with anti-Flk-1 MAb, anti-Flk-1 MAb-NP, and conventional radioimmunotherapy with Y-90-labeled anti-Flk mAb. Anti-CD31 staining showed a marked decrease in vessel density in tumors treated with anti-Flk-1 MAb-NP-Y-90, which was associated with a high level of apoptotic death in these tumors, as shown by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining. Conclusions: The present studies provide proof of principle that targeted radiotherapy works using different targeting agents on a nanoparticle, to target both the integrin alpha(v)beta(3) and the vascular endothelial growth factor receptor. These encouraging results demonstrate the potential therapeutic efficacy of the IA-NP-Y-90 and anti-Flk-1 MAb-(NPY)-Y-90-complexes as novel therapeutic agents for the treatment of a variety of tumor types. (C) 2004 Elsevier Inc. C1 Stanford Univ, Med Ctr, Dept Radiat Oncol, Stanford, CA 94305 USA. Stanford Univ, Dept Comparat Med, Stanford, CA 94305 USA. Stanford Univ, Dept Radiol, Stanford, CA 94305 USA. Targesome Inc, Palo Alto, CA USA. NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Knox, SJ (reprint author), Stanford Univ, Med Ctr, Dept Radiat Oncol, 300 Pasteur Dr, Stanford, CA 94305 USA. EM sknox@stanford.edu RI Danthi, Simhan/B-7639-2014 NR 38 TC 88 Z9 92 U1 1 U2 14 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. PD MAR 15 PY 2004 VL 58 IS 4 BP 1215 EP 1227 DI 10.1016/j.ijrob.2003.10.057 PG 13 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 801GK UT WOS:000220084200027 PM 15001266 ER PT J AU Dundr, M Hebert, MD Karpova, TS Stanek, D Xu, HZ Shpargel, KB Meier, UT Neugebauer, KM Matera, AG Misteli, T AF Dundr, M Hebert, MD Karpova, TS Stanek, D Xu, HZ Shpargel, KB Meier, UT Neugebauer, KM Matera, AG Misteli, T TI In vivo kinetics of Cajal body components SO JOURNAL OF CELL BIOLOGY LA English DT Article DE Cajal body; gems; coilin; SMN; iFRAP ID SPINAL MUSCULAR-ATROPHY; GREEN FLUORESCENT PROTEIN; SMALL NUCLEAR RNAS; COILED BODIES; SNRNP PROTEIN; GENE-PRODUCT; CANCER-CELLS; SMN PROTEIN; COMPLEX; LOCALIZATION AB Cajal bodies (CBs) are subnuclear domains implicated in small nuclear ribonucleoprotein (snRNP) biogenesis. in most cell types, CBs coincide with nuclear gems, which contain the survival of motor neurons (SMN) complex, an essential snRNP assembly factor. Here, we analyze the exchange kinetics of multiple components of CBs and gems in living cells using photobleaching microscopy. We demonstrate differences in dissociation kinetics of CB constituents and relate them to their functions. Coilin and SMN complex members exhibit relatively long CB residence times, whereas components of snRNPs, small nucleolar RNPs, and factors shared with the nucleolus have significantly shorter residence times. Comparison of the dissociation kinetics of these shared proteins from either the nucleolus or the CB suggests the existence of compartment-specific retention mechanisms. The dynamic properties of several CB components do not depend on their interaction with coilin because their dissociation kinetics are unaltered in residual nuclear bodies of coilin knockout cells. Photobleaching and fluorescence resonance energy transfer experiments demonstrate that coilin and SMN can interact within CBs, but their interaction is not the major determinant of their residence times. These results suggest that CBs and gems are kinetically independent structures. C1 NCI, NIH, Bethesda, MD 20892 USA. NCI, Fluorescence Imaging Facil, Bethesda, MD 20892 USA. Univ Mississippi, Med Ctr, Jackson, MS 39216 USA. Case Western Reserve Univ, Sch Med, Cleveland, OH 44106 USA. Max Planck Inst Mol Cell Biol & Genet, D-03107 Dresden, Germany. Yeshiva Univ Albert Einstein Coll Med, Bronx, NY 10461 USA. RP Dundr, M (reprint author), NCI, NIH, Bethesda, MD 20892 USA. EM dundrm@mail.nih.gov; a.matera@case.edu RI Stanek, David/G-9576-2013; OI Stanek, David/0000-0002-5865-175X; Matera, A. Gregory/0000-0002-6406-0630 FU NIGMS NIH HHS [GM53034, R01 GM053034]; NINDS NIH HHS [NS41617, R01 NS041617] NR 59 TC 117 Z9 118 U1 1 U2 4 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD MAR 15 PY 2004 VL 164 IS 6 BP 831 EP 842 DI 10.1083/jcb.200311121 PG 12 WC Cell Biology SC Cell Biology GA 804HG UT WOS:000220289200005 PM 15024031 ER PT J AU Rzadzinska, AK Schneider, ME Davies, C Riordan, GP Kachar, B AF Rzadzinska, AK Schneider, ME Davies, C Riordan, GP Kachar, B TI An actin molecular treadmill and myosins maintain stereocilia functional architecture and self-renewal SO JOURNAL OF CELL BIOLOGY LA English DT Article DE hair cells; myosin XVa; myosin VIIa; espin; hearing ID HAIR-CELL STEREOCILIA; BUNDLING PROTEINS; FILAMENTS; POLYMERIZATION; ORGANIZATION; DYNAMICS; MOTILITY; HAPPENS; MOUSE; SHAPE AB W e have previously shown that the seemingly static paracrystalline actin core of hair cell stereocilia undergoes continuous turnover. Here, we used the same approach of transfecting hair cells with actin-green fluorescent protein (GFP) and espin-GFP to characterize the turnover process. Actin and espin are incorporated at the paracrystal tip and flow rearwards at the same rate. The flux rates (similar to0.002-0.04 actin subunits s(-1)) were proportional to the stereocilia length so that the entire staircase stereocilia bundle was turned over synchronously. Cytochalasin D caused stereocilia to shorten at rates matching paracrystal turnover. Myosins VI and VIIa were localized alongside the actin paracrystal, whereas myosin XVa was observed at the tips at levels proportional to stereocilia lengths. Electron microscopy analysis of the abnormally short stereocilia in the shaker 2 mice did not show the characteristic tip density. We argue that actin renewal in the paracrystal follows a treadmill mechanism, which, together with the myosins, dynamically shapes the functional architecture of the stereocilia bundle. C1 NIDOCD, Sect Struct Cell Biol, NIH, Bethesda, MD 20892 USA. RP Kachar, B (reprint author), NIDOCD, Sect Struct Cell Biol, NIH, Bldg 50,Rm 4249,50 South Dr, Bethesda, MD 20892 USA. EM Kacharb@nidcd.nih.gov NR 30 TC 186 Z9 191 U1 1 U2 10 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD MAR 15 PY 2004 VL 164 IS 6 BP 887 EP 897 DI 10.1083/jcb.200310055 PG 11 WC Cell Biology SC Cell Biology GA 804HG UT WOS:000220289200010 PM 15024034 ER PT J AU Xie, RH Bryant, GW Sun, GY Nicklaus, MC Heringer, D Frauenheim, T Manaa, MR Smith, VH Araki, Y Ito, O AF Xie, RH Bryant, GW Sun, GY Nicklaus, MC Heringer, D Frauenheim, T Manaa, MR Smith, VH Araki, Y Ito, O TI Excitations, optical absorption spectra, and optical excitonic gaps of heterofullerenes. 1. C-60, C59N+, and C48N12: Theory and experiment SO JOURNAL OF CHEMICAL PHYSICS LA English DT Review ID DENSITY-FUNCTIONAL THEORY; FREQUENCY-DEPENDENT POLARIZABILITIES; ELECTRONIC EXCITATIONS; SILICON NANOCRYSTALS; SI NANOCRYSTALS; RESPONSE THEORY; SOLID C-60; HYDROAZAFULLERENE C59HN; AZAFULLERENE C48N12; QUANTUM CONFINEMENT AB Low-energy excitations and optical absorption spectrum of C-60 are computed by using time-dependent (TD) Hartree-Fock, TD-density functional theory (TD-DFT), TD DFT-based tight-binding (TD-DFT-TB), and a semiempirical Zerner intermediate neglect of diatomic differential overlap method. A detailed comparison of experiment and theory for the excitation energies, optical gap, and absorption spectrum of C-60 is presented. It is found that electron correlations and correlation of excitations play important roles in accurately assigning the spectral features of C-60, and that the TD-DFT method with nonhybrid functionals or a local spin density approximation leads to more accurate excitation energies than with hybrid functionals. The level of agreement between theory and experiment for C-60 justifies similar calculations of the excitations and optical absorption spectrum of a monomeric azafullerene cation C59N+, to serve as a spectroscopy reference for the characterization of carborane anion salts. Although it is an isoelectronic analogue to C-60, C59N+ exhibits distinguishing spectral features different from C-60: (1) the first singlet is dipole-allowed and the optical gap is redshifted by 1.44 eV; (2) several weaker absorption maxima occur in the visible region; (3) the transient triplet-triplet absorption at 1.60 eV (775 nm) is much broader and the decay of the triplet state is much faster. The calculated spectra of C59N+ characterize and explain well the measured ultraviolet-visible (UV-vis) and transient absorption spectra of the carborane anion salt [C59N][Ag(CB11H6Cl6)(2)] [Kim et al., J. Am. Chem. Soc. 125, 4024 (2003)]. For the most stable isomer of C48N12, we predict that the first singlet is dipole-allowed, the optical gap is redshifted by 1.22 eV relative to that of C-60, and optical absorption maxima occur at 585, 528, 443, 363, 340, 314, and 303 nm. We point out that the characterization of the UV-vis and transient absorption spectra of C48N12 isomers is helpful in distinguishing the isomer structures required for applications in molecular electronics. For C59N+ and C48N12 as well as C-60, TD-DFT-TB yields reasonable agreement with TD-DFT calculations at a highly reduced cost. Our study suggests that C-60, C59N+, and C48N12, which differ in their optical gaps, have potential applications in polymer science, biology, and medicine as single-molecule fluorescent probes, in photovoltaics as the n-type emitter and/or p-type base of a p-n junction solar cell, and in nanoelectronics as fluorescence-based sensors and switches. (C) 2004 American Institute of Physics. C1 Natl Inst Stand & Technol, Gaithersburg, MD 20899 USA. NCI, Med Chem Lab, NIH, Frederick, MD 21702 USA. Univ Paderborn, Dept Theoret Phys, D-33098 Paderborn, Germany. Lawrence Livermore Natl Lab, Energet Mat Ctr, Livermore, CA 94551 USA. Queens Univ, Dept Chem, Kingston, ON K7L 3N6, Canada. Tohoku Univ, Inst Multidisciplinary Res Adv Mat, Sendai, Miyagi 9808577, Japan. RP Natl Inst Stand & Technol, Gaithersburg, MD 20899 USA. EM rhxie@nist.gov RI Nicklaus, Marc/N-4183-2014; Frauenheim, Thomas/C-5653-2015; Araki, Yasuyuki/N-5281-2016 OI Frauenheim, Thomas/0000-0002-3073-0616; NR 116 TC 50 Z9 51 U1 3 U2 38 PU AMER INST PHYSICS PI MELVILLE PA 1305 WALT WHITMAN RD, STE 300, MELVILLE, NY 11747-4501 USA SN 0021-9606 EI 1089-7690 J9 J CHEM PHYS JI J. Chem. Phys. PD MAR 15 PY 2004 VL 120 IS 11 BP 5133 EP 5147 DI 10.1063/1.1647532 PG 15 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 803IO UT WOS:000220225000019 PM 15267383 ER PT J AU Byrd, JC Ruppert, AS Mrozek, K Carroll, AJ Edwards, CG Arthur, DC Pettenatti, MJ Stamberg, J Koduru, PRK Moore, JO Mayer, RJ Davey, FR Larson, RA Bloomfield, CD AF Byrd, JC Ruppert, AS Mrozek, K Carroll, AJ Edwards, CG Arthur, DC Pettenatti, MJ Stamberg, J Koduru, PRK Moore, JO Mayer, RJ Davey, FR Larson, RA Bloomfield, CD TI Repetitive cycles of high-dose cytarabine benefit patients with acute myeloid leukemia and inv(16)(p13q22) or t(16;16)(p13;q22): Results from CALGB 8461 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID ACUTE MYELOGENOUS LEUKEMIA; INTENSIVE POSTREMISSION CHEMOTHERAPY; ACUTE NONLYMPHOCYTIC LEUKEMIA; ACUTE MYELOMONOCYTIC LEUKEMIA; AML COOPERATIVE GROUP; CYTOSINE-ARABINOSIDE; CYTOGENETIC ABNORMALITIES; CUMULATIVE INCIDENCE; PROGNOSTIC VALUE; THERAPY AB Purpose To study the impact of repetitive (three to four courses) versus a single course of high-dose cytarabine (HDAC) consolidation therapy on outcome of patients with acute myeloid leukemia (AML) and nv(16)(p13q22) or t(16;16)(p13;q22). Patients and Methods We examined the cumulative incidence of relapse (CIR), relapse-free survival (RFS), and overall survival (OS) for 48 adults younger than 60 years with inv(16)/t(16;16) who had attained a complete remission on one of four consecutive clinical trials and were assigned to receive HDAC consolidation therapy. Twenty-eight patients were assigned to either three or four courses of HDAC, and 20 patients were assigned to one Course of HDAC followed by alternative intensive consolidation therapy. Results Pretreatment features were similar for the two groups. The CIR was significantly decreased in patients assigned to receive three to four cycles of HDAC compared with patients assigned to one course (P = .03; 5-year CIR, 43% v70%, respectively). The difference in RFS also approached statistical significance (P = .06). In a multivariable analysis that adjusted for potential confounding covariates, only treatment assignment (three to four cycles of HDAC) predicted for superior RFS (P = .02). The OS of both groups was similar (P = .93, 5-year OS, 75% for the three to four cycles of HDAC group v70% for the one cycle of HDAC group), reflecting a high success rate with stem-cell transplantation salvage treatment administered among patients in both treatment groups. Conclusion We conclude that, in AML patients with inv(16)/t(16;16), repetitive HDAC therapy decreases the likelihood of relapse compared with consolidation regimens including less HDAC. C1 Ohio State Univ, Div Hematol & Oncol, Columbus, OH 43210 USA. Duke Univ, Med Ctr, Durham, NC USA. Wake Forest Univ, Ctr Med, Winston Salem, NC 27109 USA. Univ Alabama, Birmingham, AL USA. Natl Canc Inst, Bethesda, MD USA. Univ Maryland, Ctr Canc, Baltimore, MD 21201 USA. N Shore Univ Hosp, Manhasset, NY USA. SUNY Upstate Med Univ, Syracuse, NY USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Chicago, Chicago, IL 60637 USA. RP Byrd, JC (reprint author), Ohio State Univ, Div Hematol & Oncol, B302A Starling Loving Hall,320 W 10th Ave, Columbus, OH 43210 USA. EM byrd-3@medctr.osu.edu RI Mrozek, Krzysztof/A-3142-2008; OI Larson, Richard/0000-0001-9168-3203 FU NCI NIH HHS [CA101140, CA16058, CA31946, CA77658] NR 33 TC 107 Z9 112 U1 1 U2 1 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 MAR 15 PY 2004 VL 22 IS 6 BP 1087 EP 1094 DI 10.1200/JCO.2004.07.012 PG 8 WC Oncology SC Oncology GA 804GT UT WOS:000220287900018 PM 15020610 ER PT J AU Akimov, SA Kuzmin, PI Zimmerberg, J Cohen, FS Chizmadzhev, YA AF Akimov, SA Kuzmin, PI Zimmerberg, J Cohen, FS Chizmadzhev, YA TI An elastic theory for line tension at a boundary separating two lipid monolayer regions of different thickness SO JOURNAL OF ELECTROANALYTICAL CHEMISTRY LA English DT Article DE lipid monolayer; raft; line tension; lipid tilt; liquid ordered domain ID GANGLIOSIDE GM1; RAFTS; MEMBRANES; DOMAINS; MODEL; CHOLESTEROL; TILT AB To study theoretically the physics of the interface between liquid ordered ("raft") and liquid disordered domains in biological cells and bilayer lipid membranes, we approximated this complex system by considering the energetics of one planar lipid monolayer leaflet at the interface between two regions of different thickness. Because it is energetically unfavorable to expose the hydrophobic lipid tails of the thicker region to water, lipid molecules deform near the interface in order to diminish the area of the acyl chain-water contact. This deformation is used to calculate the interfacial line tension. Leaflets are treated as a continuous elastic medium and the spatial distribution of deformations and the line tension are obtained by minimizing the total (elastic and hydrophobic) energy of the monolayer. Using reasonable values of elastic and spatial parameters, we found that lipid deformation completely eliminates any hydrophobic contact with water due to thickness differences. The energy of the system is therefore determined exclusively by the elastic deformation of the monolayer. Lipid deformations occur over a narrow region of similar to2-4 nm near the interface boundary. The value of the monolayer line tension is calculated to be similar to0.5kT/nm for a similar to0.5 nm difference in monolayer thickness. This value of the line tension is sufficient to maintain the circular shape of cholesterol-sphingolipid domains observed in lipid bilayer membranes. The energy of interaction of two thick domains separated by a thinner domain is obtained: thick domains attract from a distance of 1-2 nm. (C) 2003 Elsevier B.V. All rights reserved. C1 Russian Acad Sci, AN Frumkin Electrochem Inst, Lab Bioelectrochem, Moscow 119071, Russia. NICHHD, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. Rush Med Coll, Dept Mol Biophys & Physiol, Chicago, IL 60612 USA. RP Chizmadzhev, YA (reprint author), Russian Acad Sci, AN Frumkin Electrochem Inst, Lab Bioelectrochem, Bldg 5,31 Leninsky Prospect, Moscow 119071, Russia. EM chiz@fromru.com RI Chizmadzhev, Yuri/L-1984-2013; Akimov, Sergey/L-2001-2013; Akimov, Sergey/I-6432-2015 NR 16 TC 50 Z9 52 U1 0 U2 4 PU ELSEVIER SCIENCE SA PI LAUSANNE PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND SN 0022-0728 J9 J ELECTROANAL CHEM JI J. Electroanal. Chem. PD MAR 15 PY 2004 VL 564 IS 1-2 BP 13 EP 18 DI 10.1016/j.jelechem.2003.10.030 PG 6 WC Chemistry, Analytical; Electrochemistry SC Chemistry; Electrochemistry GA 801LR UT WOS:000220097900002 ER PT J AU Vogt, A Chuang, PT Hebert, J Hwang, J Lu, Y Kopelovich, L Athar, M Bickers, DR Epstein, EH AF Vogt, A Chuang, PT Hebert, J Hwang, J Lu, Y Kopelovich, L Athar, M Bickers, DR Epstein, EH TI Immunoprevention of basal cell carcinomas with recombinant hedgehog-interacting protein SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE basal cell nevus syndrome; patched; skin cancer; immunization; mouse ID IMIQUIMOD 5-PERCENT CREAM; CYTOTOXIC T-LYMPHOCYTES; SONIC HEDGEHOG; CPG-DNA; AUTOIMMUNE-DISEASE; TUMOR REJECTION; HUMAN HOMOLOG; EXPRESSION; ANTIGEN; MICE AB Basal cell carcinomas (BCCs) are driven by abnormal hedgehog signaling and highly overexpress several hedgehog target genes. We report here our use of one of these target genes, hedgehog-interacting protein (Hip1), as a tumor-associated antigen for immunoprevention of BCCs in Ptchl(+/-) mice treated with ionizing radiation. Hip 1 rnRNA is expressed in adult mouse tissues at levels considerably lower than those in BCCs. Immunization with either of two large recombinant Hip1 polypeptides was well tolerated in Ptch1(+/-) mice, induced B and T cell responses detectable by enzyme-linked immunosorbent assay, Western blot, delayed type hypersensitivity, and enzyme-linked immunospot assay, and reduced the number of BCCs by 42% (P < 0.001) and 32% (P < 0.01), respectively. We conclude that immunization with proteins specifically up-regulated by hedgehog signaling may hold promise as a preventive option for patients such as those with the basal cell nevus syndrome who are destined to develop large numbers of BCCs. C1 Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA. Univ Calif San Francisco, Ctr Comprehens Canc, San Francisco, CA 94143 USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. Columbia Univ, Dept Dermatol, New York, NY 10032 USA. RP Epstein, EH (reprint author), Univ Calif San Francisco, San Francisco Gen Hosp, 1001 Potrero Ave,Bldg 100,Rm 269, San Francisco, CA 94110 USA. EM epsteine@derm.ucsf.edu FU NCI NIH HHS [U19 CA081888, U19 CA81888] NR 47 TC 24 Z9 24 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD MAR 15 PY 2004 VL 199 IS 6 BP 753 EP 761 DI 10.1084/jem.20031190 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 804YW UT WOS:000220335000002 PM 15024045 ER PT J AU Rogozin, IB Diaz, M AF Rogozin, IB Diaz, M TI Cutting edge: DGYW/WRCH is a better predictor of mutability at G : C bases in Ig hypermutation than the widely accepted RGYW/WRCY motif and probably reflects a two-step activation-induced cytidine deaminase-triggered process SO JOURNAL OF IMMUNOLOGY LA English DT Article ID SINGLE-STRANDED-DNA; SOMATIC HYPERMUTATION; ANTIBODY DIVERSIFICATION; IMMUNOGLOBULIN GENES; MUTATION HOTSPOTS; POLYMERASE-ZETA; AID; SEQUENCES; MUTAGENESIS; MECHANISM AB A feature of Ig hypermutation is the presence of hypermutable DNA sequences that are preferentially found in the V regions of Ig genes. Among these, RGYW/WRCY is the most pronounced motif (G.-C is a mutable position; R = A/G, Y = C/T and W = A/T). However, a molecular basis for the high mutability of RGYW was not known until recently. The discovery that activation-induced cytidine deaminase targets the DNA encoding V regions, has enabled the analysis of its targeting properties when expressed outside of the context of hypermutation. We analyzed these data and found evidence that activation-induced cytidine deaminase is the major source of the RGYW mutable motif, but with a new twist: DGYW/WRCH (G:C is the mutable position; D = A/G/T, H = T/C/A) is a better descriptor of the Ig mutation hotspot than RGYW/WRCY We also found evidence that a DNA repair enzyme may play a role in modifying the sequence of hypermutation hotspots. C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. NIEHS, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Rogozin, IB (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 38A,Room 5N505A,8600 Rockville Pike, Bethesda, MD 20894 USA. EM rogozin@ncbi.nlm.nih.gov; diaz@niehs.nih.gov NR 29 TC 99 Z9 101 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 MAR 15 PY 2004 VL 172 IS 6 BP 3382 EP 3384 PG 3 WC Immunology SC Immunology GA 801KY UT WOS:000220096000005 PM 15004135 ER PT J AU Alaniz, RC Sandall, S Thomas, EK Wilson, CB AF Alaniz, RC Sandall, S Thomas, EK Wilson, CB TI Increased dendritic cell numbers impair protective immunity to intracellular bacteria despite augmenting antigen-specific CD8(+) T lymphocyte responses SO JOURNAL OF IMMUNOLOGY LA English DT Article ID LISTERIA-MONOCYTOGENES INFECTION; MYCOBACTERIUM-TUBERCULOSIS INFECTION; LIGAND-TREATED MICE; FLT3 LIGAND; IN-VIVO; RECEPTOR EXPRESSION; ANTITUMOR IMMUNITY; IFN-GAMMA; MACROPHAGES; MATURATION AB Dendritic cells (DCs) reside in tissues, where they function as sentinels, providing an essential link between innate and adaptive immunity. Increasing the numbers of DCs in vivo augments T cell responses, and can cause dramatic CTL-dependent tumor regression. To determine whether greater DC numbers promoted T cell-mediated protection in the context of host defense against intracellular bacteria, we treated mice with Flt3 ligand (Flt3-L) to increase DCs in vivo and challenged them with Listeria monocytogenes. Unexpectedly, after primary challenge with Listeria, the overall control of Listeria infection was impaired in Flt3-L-treated mice, which had greater bacterial burden and mortality than controls. Similar results were obtained when DC numbers were increased by treatment with polyethylene glycol-conjugated GM-CSF rather than Flt3-L and in mice infected with Mycobacterium tuberculosis. Impaired protection was not due to dysfunctional T cell responses, as Flt3-L-treated mice had a greater frequency and absolute number of Ag-specitic CD8(+) T cells, which produced IFN-gamma, exhibited cytolytic activity, and transferred protection. The increased Listeria burden in Flt3-L-treated mice was preferentially associated with DCs, which were unable to kill Listeria and more resistant to CTL lysis compared with macrophages in vitro. Although we cannot exclude the possibility that other potential effects, in addition to increased numbers of DCs, are shared by Flt3-L and polyethylene glycol-conjugated GM-CSF and contributed to the increase in susceptibility observed in treated mice, these results support the notion that DC numbers must be properly controlled within physiological limits to optimize host defense to intracellular bacterial pathogens. C1 Univ Washington, Dept Immunol, Seattle, WA 98195 USA. Univ Washington, NHLBI, Stipends Training Aspiring Researchers Program, Seattle, WA 98195 USA. Amgen Inc, Seattle, WA 98101 USA. RP Wilson, CB (reprint author), Univ Washington, Dept Immunol, Box 357650,1959 NE Pacific St, Seattle, WA 98195 USA. EM cbwilson@u.washington.edu FU NICHD NIH HHS [HD18184] NR 69 TC 34 Z9 38 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 MAR 15 PY 2004 VL 172 IS 6 BP 3725 EP 3735 PG 11 WC Immunology SC Immunology GA 801KY UT WOS:000220096000047 PM 15004177 ER PT J AU McCartney-Francis, N Jin, WW Wahl, SM AF McCartney-Francis, N Jin, WW Wahl, SM TI Aberrant toll receptor expression and endotoxin hypersensitivity in mice lacking a functional TGF-beta 1 signaling pathway SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NF-KAPPA-B; INFLAMMATORY-BOWEL-DISEASE; TGF-BETA; KNOCKOUT MICE; SEPTIC SHOCK; IN-VIVO; ACTIVATION; TLR4; MUTATIONS; PROTEASOME AB TGF-beta1 plays a central role in maintaining normal immune function and deficiency of this potent immunosuppressive molecule is linked to uncontrolled inflammation, cachexia, and multiorgan failure as seen in the TGF-beta1 null mouse. Infiltration of inflammatory cells into vital organs of the null mouse is accompanied by increased gene expression of inflammatory cytokines, including TNF-alpha and IL-1beta, as well as inducible NO synthase, each regulated by NF-kappaB. Treatment with the proteasome inhibitor MG132 to prevent NF-kappaB activation dramatically reduced NO production and expression of inflammatory cytokines. This inflammatory phenotype with NF-kappaB activation in the TGF-beta1 null mouse, in the absence of any identifiable pathogen, suggested activation of innate immune responses. Because Toll-like receptors (TLR) are essential in the activation of innate immunity, we examined inflamed tissue from TGF-beta1 null and wild-type mice for expression of TLR4, the receptor that interacts with bacterial cell wall LPS to initiate an NF-kappaB-dependent signaling pathway, leading to gene transcription of inflammatory mediators. Increased TLR4 mRNA expression observed in TGF-beta1 null mice as well as in mice lacking the TGF-beta transcription factor Smad3 was associated with LPS hyperresponsiveness leading to increased expression of inflammatory cytokines and NO and endotoxemia. Furthermore, mice lacking both TGF-beta1 and a functional TLR4 were resistant to endotoxin shock. Constitutive and/or environmental activation of TLR4 and downstream elements, in the absence of TGF-beta suppression, may impact on innate and adaptive immunity and contribute to massive uncontrolled inflammation. C1 Natl Inst Dent & Craniofacial Res, Cellular Immunol Sect, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. RP McCartney-Francis, N (reprint author), Natl Inst Dent & Craniofacial Res, Cellular Immunol Sect, Oral Infect & Immun Branch, NIH, Bldg 30,Room 326,30 Convent Dr, Bethesda, MD 20892 USA. EM nfrancis@dir.nidcr.nih.gov NR 43 TC 72 Z9 78 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 15 PY 2004 VL 172 IS 6 BP 3814 EP 3821 PG 8 WC Immunology SC Immunology GA 801KY UT WOS:000220096000057 PM 15004187 ER PT J AU Bielekova, B Sung, MH Kadom, N Simon, R McFarland, H Martin, R AF Bielekova, B Sung, MH Kadom, N Simon, R McFarland, H Martin, R TI Expansion and functional relevance of high-avidity myelin-specific CD4(+) T cells in multiple sclerosis SO JOURNAL OF IMMUNOLOGY LA English DT Article ID BASIC-PROTEIN EPITOPE; PROTEOLIPID PROTEIN; HEALTHY-INDIVIDUALS; RECEPTOR REPERTOIRE; NEGATIVE SELECTION; PERIPHERAL-BLOOD; IMMUNE-RESPONSE; AMINO-ACIDS; ANTIGEN; RECOGNITION AB Multiple sclerosis (MS) is an autoimmune disease in which myelin-specific T cells are believed to play a crucial pathogenic role. Nevertheless, so far it has been extremely difficult to demonstrate differences in T cell reactivity to myelin Ag between MS patients and controls. We believe that by using unphysiologically high Ag concentrations previous studies have missed a highly relevant aspect of autoimmune responses, i.e., T cells recognizing Ag with high functional avidity. Therefore, we focused on the characterization of high-avidity myelin-specific CD4(+) T cells in a large cohort of MS patients and controls that was matched demographically and with respect to expression of MHC class II alleles. We demonstrated that their frequency is significantly higher in MS patients while the numbers of control T cells specific for influenza hemagglutinin are virtually identical between the two cohorts; that high-avidity T cells are enriched for previously in vivo-activated cells and are significantly skewed toward a proinflammatory phenotype. Moreover, the immunodominant epitopes that were most discriminatory between MS patients and controls differed from those described previously and were clearly biased toward epitopes with lower predicted binding affinities to HLA-DR molecules, pointing at the importance of thymic selection for the generation of the autoimmune T cell repertoire. Correlations between selected immunological parameters and magnetic resonance imaging markers indicate that the specificity and function of these cells influences phenotypic disease expression. These data have important implications for autoimmunity research and should be considered in the development of Ag-specific therapies in MS. C1 NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. NCI, Biometr Res Branch, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. RP Martin, R (reprint author), NINDS, Neuroimmunol Branch, NIH, Bldg 10,Room 5B-16,10 Ctr Dr,MSC 1400, Bethesda, MD 20892 USA. EM martinr@ninds.nih.gov NR 51 TC 125 Z9 125 U1 1 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 15 PY 2004 VL 172 IS 6 BP 3893 EP 3904 PG 12 WC Immunology SC Immunology GA 801KY UT WOS:000220096000067 PM 15004197 ER PT J AU Barton, LF Runnels, HA Schell, TD Cho, YJ Gibbons, R Tevethia, SS Deepe, GS Monaco, JJ AF Barton, LF Runnels, HA Schell, TD Cho, YJ Gibbons, R Tevethia, SS Deepe, GS Monaco, JJ TI Immune defects in 28-kDa proteasome activator gamma-deficient mice SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-LYMPHOCYTE EPITOPE; MHC CLASS-I; 20S PROTEASOME; ANTIGEN PRESENTATION; HISTOPLASMA-CAPSULATUM; INTERFERON-GAMMA; REG-ALPHA; PULMONARY HISTOPLASMOSIS; MULTICATALYTIC PROTEASE; PA28 AB Protein complexes of the 28-kDa proteasome activator (PA28) family activate the proteasome and may alter proteasome cleavage specificity. Initial investigations have demonstrated a role for the IFN-gamma-inducible PA28alpha/beta complex in Ag processing. Although the noninducible and predominantly nuclear PA28gamma complex has been implicated in affecting proteasome-dependent signaling pathways, such as control of the mitotic cell cycle, there is no previous evidence demonstrating a role for this structure in Ag processing. We therefore generated PA28gamma-deficient mice and investigated their immune function. PA28gamma(-/-) mice display a slight reduction in CD8(+) T cell numbers and do not effectively clear a pulmonary fungal infection. However, T cell responses in two viral infection models appear normal in both magnitude and the hierarchy of antigenic epitopes recognized. We conclude that PA28gamma(-/-) mice, like PA28alpha(-/-)/beta(-/-) mice, are deficient in the processing of only specific Ags. C1 Univ Cincinnati, Dept Mol Genet Biochem & Microbiol, Cincinnati, OH 45267 USA. Univ Cincinnati, Howard Hughes Med Inst, Cincinnati, OH 45267 USA. Univ Cincinnati, Div Infect Dis, Dept Internal Med, Cincinnati, OH 45267 USA. Penn State Univ, Milton S Hershey Coll Med, Dept Microbiol & Immunol, Hershey, PA 17033 USA. NIAID, Viral Immunol Sect, NIH, Bethesda, MD 20892 USA. RP Monaco, JJ (reprint author), Univ Cincinnati, Coll Med, Dept Mol Genet, 231 Albert Sabin Way, Cincinnati, OH 45267 USA. EM monacojj@ucmail.uc.edu FU NCI NIH HHS [CA25000]; NIAID NIH HHS [AI34361, AI42747] NR 48 TC 63 Z9 69 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 15 PY 2004 VL 172 IS 6 BP 3948 EP 3954 PG 7 WC Immunology SC Immunology GA 801KY UT WOS:000220096000073 PM 15004203 ER PT J AU Rajendran, M Inbaraj, JJ Gandhidasan, R Murugesan, R AF Rajendran, M Inbaraj, JJ Gandhidasan, R Murugesan, R TI Photodynamic action of damnacanthal and nordamnacanthal SO JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY A-CHEMISTRY LA English DT Article DE 5,5-dimethyl-1-pyrroline-N-oxide; damnacanthal; singlet oxygen; superoxide anion radical; molecular modelling ID SINGLET OXYGEN PRODUCTION; PROTEIN-KINASE; ANTICANCER AGENTS; MOLECULAR-OXYGEN; SEMIQUINONE; CELLS; PHOTOSENSITIZATION; ILLUMINATION; INHIBITORS; ACTIVATION AB Photodynamic properties of two anthraquinones, damnacanthal (DAM) and nordamnacanthal (NDAM) are studied. Photogeneration of singlet oxygen is monitored by both optical, and EPR methods. In comparison with rose bengal (Phi(1)O(2) for RB = 0.76), singlet oxygen generating efficiencies of DAM and NDAM are determined to be 0.29 and 0.10, respectively. Rate of RNO bleaching is found to be retarded by specific O-1(2) quenchers such as DABCO and NaN3, confirming the involvement of O-1(2) as an active intermediate. Photolysis of DAM and NDAM in DMSO, in the presence of spin trap 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) generates 12-line EPR spectra, characteristic of O-2(.-) adduct. Photogeneration of O-2(.-) is also monitored by optical spectroscopy using SOD inhibitable cytochrome c reduction assay. Our results indicate that DAM possesses high ability to generate reactive oxygen species. Both Type I and Type II paths are involved in the photosensitisation of DAM as well as NDAM. The quantum mechanically calculated lowest unoccupied molecular orbital (LUMO) energies of DAM and NDAM are correlated with the experimental redox potential. (C) 2004 Elsevier B.V. All rights reserved. C1 Madurai Kamaraj Univ, Sch Chem, Madurai 625021, Tamil Nadu, India. NIEHS, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. NMSSVN Coll, Dept Chem, Madurai 625019, Tamil Nadu, India. RP Murugesan, R (reprint author), Madurai Kamaraj Univ, Sch Chem, Madurai 625021, Tamil Nadu, India. EM rammurugesan@yahoo.com NR 48 TC 6 Z9 6 U1 1 U2 4 PU ELSEVIER SCIENCE SA PI LAUSANNE PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND SN 1010-6030 J9 J PHOTOCH PHOTOBIO A JI J. Photochem. Photobiol. A-Chem. PD MAR 15 PY 2004 VL 162 IS 2-3 BP 615 EP 623 DI 10.1016/S1010-6030(03)00415-5 PG 9 WC Chemistry, Physical SC Chemistry GA 806YF UT WOS:000220468500049 ER PT J AU Yang, YL Li, CCH Weissman, AM AF Yang, YL Li, CCH Weissman, AM TI Regulating the p53 system through ubiquitination SO ONCOGENE LA English DT Review DE p53; Mdm2; ubiquitination; molecular targeting; apoptosis ID TUMOR-SUPPRESSOR PROTEIN; EARLY EMBRYONIC LETHALITY; PROLYL ISOMERASE PIN1; STABILIZES P53; MUTANT P53; IN-VIVO; DOWN-REGULATION; DNA-DAMAGE; P53-DEPENDENT APOPTOSIS; MDM2-DEFICIENT MICE AB The tumor suppressor p53 is tightly controlled at low levels in cells by constant ubiquitination and proteasomal degradation. In response to stresses, ubiquitination of p53 is inhibited through diverse pathways, depending on the nature of the stimulus and cell type. This leads to the accumulation and activation of p53, which induces cell cycle arrest and/or apoptosis to prevent cells from transformation. Many studies have indicated that defects of the p53 system are present in most, if not all, human tumor cells. Meanwhile, significant progress has been made in understanding the molecular mechanisms of p53 ubiquitination and the regulation of the p53 system. Therefore, it is possible now to consider targeting ubiquitination as a means to regulate and reactivate p53 in tumors. Emerging evidence suggests that inhibiting the E3 activity of Mdm2, blocking the interaction of p53 and Mdm2, and restoring the function of mutated p53 are potential effective strategies to kill certain tumor cells selectively. It is conceivable that new chemotherapeutic agents based on these studies will be generated in the not-so-distant future. C1 NCI, Regulat Prot Funct Lab, Ctr Canc Res, Frederick, MD 21702 USA. NCI, Lab Canc Prevent, SAIC Frederick, NIH, Frederick, MD 21702 USA. RP Yang, YL (reprint author), NCI, Regulat Prot Funct Lab, Ctr Canc Res, 1050 Boyles St,560-22-64, Frederick, MD 21702 USA. EM yangyili@ncifcrf.gov FU NCI NIH HHS [N01-CA-12400] NR 129 TC 118 Z9 129 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAR 15 PY 2004 VL 23 IS 11 BP 2096 EP 2106 DI 10.1038/sj.onc.1207411 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 803EC UT WOS:000220213400014 PM 15021897 ER PT J AU Gau, SSF Merikangas, KR AF Gau, SSF Merikangas, KR TI Similarities and differences in sleep-wake patterns among adults and their children SO SLEEP LA English DT Article DE parent-child association; sleep-wake patterns; evening type; mood status ID JAPANESE WORKERS; MORNINGNESS-EVENINGNESS; PSYCHIATRIC-DISORDERS; DAYTIME SLEEPINESS; PANIC DISORDER; NONDEPRESSED PATIENTS; EARLY ADOLESCENCE; OBESE CHILDREN; SHIFT SCHEDULE; DISTURBANCE AB Study Objective: To determine associations and differences in sleep-wake patterns among children and their parents and to explore the correlates for sleep-wake patterns among adults. Design: A school-based cross-sectional survey. Participants: Sample included 1479 fourth to eighth graders and their parents, using a multistage sampling method. Interventions: N/A. Measurements and Results: Students and their parents completed a Sleep Habit Questionnaire, which included sleep schedules, a mood scale, and the morningness/eveningness scale. Statistical methods included Pearson and Spearman correlations and analysis of variance using a mixed model. Results showed low correlations in sleep schedules and sleep-wake patterns between children and those parents who did not work shifts or have an evening or night job. Compared to their children, parents tended to go to bed and rise later, have shorter nighttime sleep duration, have less weekend compensation of sleep, and have the morning-type sleep profile. In addition, junior-high students (seventh and eight graders) demonstrated different sleep-wake patterns compared to elementary-school students (fourth to sixth graders). Young age, moodiness, and shift work were associated with tendencies to be the evening type among parent participants. Conclusions: Our findings indicate that age, social demands (school work for children and adolescents and employment type for adults), and mood status are associated with sleep-wake patterns. Future study examining the association between evening-sleep type and neurotic traits and psychopathology in the adult population will be our next step. C1 Natl Taiwan Univ Hosp, Dept Psychiat, Taipei 100, Taiwan. Natl Taiwan Univ, Coll Med, Dept Psychiat, Taipei 100, Taiwan. NIMH, Sect Dev Genet Epidemiol,Mood & Anxiety Disorders, Intramural Res Program, Natl Inst Hlth,Dept Hlth & Human Serv, Bethesda, MD USA. RP Gau, SSF (reprint author), Natl Taiwan Univ Hosp, Dept Psychiat, 7 Chung-Shan S Rd, Taipei 100, Taiwan. EM gaushufe@ntu.edu.tw OI Gau, Susan Shur-Fen/0000-0002-2718-8221 NR 75 TC 24 Z9 24 U1 1 U2 3 PU AMER ACADEMY SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CENTER STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PD MAR 15 PY 2004 VL 27 IS 2 BP 299 EP 304 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 844OT UT WOS:000223168800019 PM 15124726 ER PT J AU Karrow, NA Guo, TL Delclos, KB Newbold, RR Weis, C Germolec, DR White, KL McCay, JA AF Karrow, NA Guo, TL Delclos, KB Newbold, RR Weis, C Germolec, DR White, KL McCay, JA TI Nonylphenol alters the activity of splenic NK cells and the numbers of leukocyte subpopulations in Sprague-Dawley rats: a two-generation feeding study SO TOXICOLOGY LA English DT Article DE nonylphenol (NP); in utero exposure; immunomodulation; rat; feeding study ID ESTROGENIC ACTIVITY; RAINBOW-TROUT; EXPOSURE; 4-NONYLPHENOL; TOXICOLOGY; TOXICITY; IMMUNITY AB Nonylphenol (NP) has been identified at low levels in surface waters throughout North America. This industrial chemical is primarily used for the production of certain non-ionic surfactants, and has been reported to have weak estrogen-like activity. As estrogen has immunoregulatory properties and is crucial for normal fetal development, it was hypothesized that adult and developmental exposures to NP had the potential to adversely affect the immune system. Furthermore, developmental exposure to NP might also produce differential immunomodulation in F-1 male and female rats. Thus, a two-generation feeding study was conducted to evaluate the potential for NP to modulate certain immune parameters. Pregnant female Sprague-Dawley rats were exposed to NP (0, 25, 500, and 2000 ppm) in their feed for 65 days, beginning 7 days into gestation. The F-1 generation male and female offspring were exposed in utero at the respective treatment levels, commencing the 7th day of gestation, and continuing through to 64 days of age. Changes in splenic antibody-forming cell response, natural killer cell activity, and leukocyte numbers were used to evaluate NP immunotoxicity. The results from the present study indicate that dietary exposure to NP can increase splenic natural killer (NK) cell activity and splenocyte subpopulation numbers in the F-1 generation rats, without similar changes to the F-0 generation. The immunological changes that were observed in the F-1 generation also appeared to be gender-specific. (C) 2003 Elsevier Ireland Ltd. All rights reserved. C1 Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, Richmond, VA 23298 USA. US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. NIEHS, Mol Toxicol Lab, Res Triangle Pk, NC 27709 USA. RP White, KL (reprint author), Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, Med Coll Virginia Campus, Richmond, VA 23298 USA. EM kwhite@hsc.vcu.edu FU NIEHS NIH HHS [ES 55094] NR 23 TC 20 Z9 24 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0300-483X J9 TOXICOLOGY JI Toxicology PD MAR 15 PY 2004 VL 196 IS 3 BP 237 EP 245 DI 10.1016/j.tox.2003.11.009 PG 9 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 800EE UT WOS:000220010900007 PM 15036750 ER PT J AU Athar, M An, KP Tang, XW Morel, KD Kim, AL Kopelovich, L Bickers, DR AF Athar, M An, KP Tang, XW Morel, KD Kim, AL Kopelovich, L Bickers, DR TI Photoprotective effects of sulindac against ultraviolet B-induced phototoxicity in the skin of SKH-1 hairless mice SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE sulindac; UVB; prostaglandin; cyclooxygenase; anti-inflammatory activity; surrogate markers; phototoxicity ID CYCLOOXYGENASE-2 INHIBITOR; TOPICAL APPLICATION; TUMOR PROMOTION; PHORBOL ESTER; MOUSE SKIN; CUTANEOUS INFLAMMATION; COX-2 EXPRESSION; CARCINOGENESIS; OVEREXPRESSION; EPIDERMIS AB Sulindac is a nonsteroidal anti-inflammatory drug with demonstrated potency as a chemopreventive agent in animal models of carcinogenesis and in patients with familial adenomatous polyposis. Because tumor promotion is generally associated with exposure to proinflammatory stimuli, it is likely that anti-inflammatory agents may have potent antitumor effects. In human skin, sulindac reduces bradykinin-induced edema. In this study, we tested the hypothesis that the cyclooxygenase inhibitor sulindac can protect against ultraviolet (UVB)-induced injury that is crucial for the induction of cancer. Exposure of SKH-1 hairless mice to two consecutive doses of UVB (230 mJ/cm(2)) induces various inflammatory responses including erythema, edema, epidermal hyperplasia, infiltration of polymorphonuclear leukocytes, etc. Topical application of sulindac (1.25-5.0 mg/0.2 ml acetone) to the dorsal skin of SKH-1 hairless mice either I h before or immediately after UVB exposure substantially inhibited these inflammatory responses in a dose-dependent manner. Oral administration of sulindac in drinking water (160 ppm) for 15 days before and during UVB irradiation similarly reduced these inflammatory responses. These potent anti-inflammatory effects of sulindac suggested the possibility that the drug could inhibit signaling processes that relate to carcinogenic insult by UVB. Accordingly, studies were conducted to assess the efficacy of sulindac in attenuating the expression of UVB-induced early surrogate molecular markers of photodamage and carcinogenesis. UVB exposure enhanced the expression of p53, c-fos, cyclins D1 and A, and PCNA 24 h after irradiation. Treatment of animals with either topical or oral administration of sulindac largely abrogated the expression of these UVB-induced surrogate markers. These results indicate that the cyclooxygenase inhibitor sulindac is effective in reducing UVB-induced events relevant to carcinogenesis and that this category of topically applied or orally administered drugs may prove to be effective chemopreventive agents for reducing the risk of photocarcinogenesis in human populations. (C) 2003 Elsevier Inc. All rights reserved. C1 Columbia Univ Coll Phys & Surg, Dept Dermatol, New York, NY 10032 USA. Columbia Univ Coll Phys & Surg, Skin Dis Ctr, New York, NY 10032 USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. RP Athar, M (reprint author), Columbia Univ Coll Phys & Surg, Dept Dermatol, 630 W 168th St, New York, NY 10032 USA. EM ma493@columbia.edu FU NCI NIH HHS [R03 CA-101061, U19 CA 81888, CA-10106-01, R01 CA-97249-01, N01-CN-15109]; NIAMS NIH HHS [P30 AR 44535] NR 32 TC 23 Z9 24 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD MAR 15 PY 2004 VL 195 IS 3 BP 370 EP 378 DI 10.1016/j.taap.2003.09.030 PG 9 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 804FO UT WOS:000220284800013 PM 15020200 ER PT J AU Best, SM Bloom, ME AF Best, SM Bloom, ME TI Caspase activation during virus infection: more than just the kiss of death? SO VIROLOGY LA English DT Review ID HEPATITIS-C VIRUS; MINK DISEASE PARVOVIRUS; NUCLEOCAPSID PROTEIN; MEDIATED CLEAVAGE; APOPTOSIS; REPLICATION; INHIBITION; REGION; CELLS; 5A C1 NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, Hamilton, MT 59840 USA. RP Best, SM (reprint author), NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, 903 S 4th St, Hamilton, MT 59840 USA. EM sbest@niaid.nih.gov NR 19 TC 30 Z9 31 U1 0 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD MAR 15 PY 2004 VL 320 IS 2 BP 191 EP 194 DI 10.1016/j.virol.2003.11.025 PG 4 WC Virology SC Virology GA 804VS UT WOS:000220326800001 PM 15053016 ER PT J AU Zhang, LP Hayes, RB Guo, WH McHale, CM Yin, SN Wiencke, JK O'Neill, JP Rothman, N Li, GL Smith, MT AF Zhang, LP Hayes, RB Guo, WH McHale, CM Yin, SN Wiencke, JK O'Neill, JP Rothman, N Li, GL Smith, MT TI Lack of increased genetic damage in 1,3-butadiene-exposed Chinese workers studied in relation to EPHX1 and GST genotypes SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS LA English DT Article DE 1,3-butadiene; chromosomal aberrations; fluorescence in situ hybridization; HPRT; GSTs; EPHX1; genotypes ID MICROSOMAL EPOXIDE HYDROLASE; BUTADIENE-POLYMER WORKERS; SYNTHETIC RUBBER WORKERS; HUMAN-LYMPHOCYTES; CHROMOSOMAL-ABERRATIONS; HUMAN SENSITIVITY; LUNG-CANCER; FREQUENCY; SUSCEPTIBILITY; POLYMORPHISMS AB 1,3-Butadiene (BD) is an important industrial chemical and pollutant. Its ability to induce genetic damage and cause hematological malignancies in humans is controversial. We have examined chromosome damage by fluorescence in situ hybridization (FISH) and mutations in the HPRT gene in the blood of Chinese workers exposed to BD. Peripheral blood samples were collected and cultured from 39 workers exposed to 1313 (median level 2 ppm, 6 h time-weighted average) and 38 matched controls in Yanshan, China. No difference in the level of aneuploidy or structural changes in chromosomes 1, 7, 8, and 12 was detected in metaphase cells from exposed subjects in comparison with matched controls, nor was there an increase in the frequency of HPRT mutations in the BD-exposed workers. Because genetic polymorphisms in glutathione S-transferase (GST) enzymes and microsomal epoxide hydrolase (EPHX1) may affect the genotoxic effects of BD and its metabolites, we also related chromosome alterations and gene mutations to GSIT1, GSTM1 and EPHX1 genotypes. Overall, there was no effect of variants in these genotypes on numerical or structural changes in chromosomes 1, 7, 8 and 12 or on HPRT mutant frequency in relation to BD exposure, but the GST genotypes did influence background levels of both hyperdiploidy and HPRT mutant frequency. In conclusion, our data show no increase in chromosomal aberrations or HPRT mutations among workers exposed to BD, even in potentially susceptible genetic subgroups. The study is, however, quite small and the levels of BD exposure are not extremely high, but our findings in China do support those from a similar study conducted in the Czech Republic. Together, these studies suggest that low levels of occupational BD exposure do not pose a significant risk of genetic damage. (C) 2003 Elsevier B.V. All rights reserved. C1 Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Chinese Ctr Dis Control & Prevent, Natl Inst Occupat Hlth & Poison Control, Beijing 100050, Peoples R China. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Univ Vermont, Genet Lab, Burlington, VT 05401 USA. RP Smith, MT (reprint author), Univ Calif Berkeley, Sch Publ Hlth, 140 Warren Hall, Berkeley, CA 94720 USA. EM martynts@uclink.berkeley.edu OI Hayes, Richard/0000-0002-0918-661X FU NIEHS NIH HHS [P42 ES004705, P42ES04705] NR 32 TC 14 Z9 18 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1383-5718 J9 MUTAT RES-GEN TOX EN JI Mutat. Res. Genet. Toxicol. Environ. Mutagen. PD MAR 14 PY 2004 VL 558 IS 1-2 BP 63 EP 74 DI 10.1016/j.mrgentox.2003.11.001 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 800CP UT WOS:000220006800008 PM 15036120 ER PT J AU Kovacs, A Connors, M AF Kovacs, A Connors, M TI HIV-1 and immune control: can we change the course of HIV-1? SO LANCET LA English DT Editorial Material ID HUMAN-IMMUNODEFICIENCY-VIRUS; STRUCTURED TREATMENT INTERRUPTIONS; T-CELL DIFFERENTIATION; ANTIRETROVIRAL THERAPY; INFECTION; LYMPHOCYTES; RESPONSES; EFFECTOR; SUBSETS C1 Univ So Calif, Keck Sch Med, Maternal Child & Adolescent Ctr Infect Dis & Viro, Los Angeles, CA 90033 USA. NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Kovacs, A (reprint author), Univ So Calif, Keck Sch Med, Maternal Child & Adolescent Ctr Infect Dis & Viro, Los Angeles, CA 90033 USA. NR 18 TC 6 Z9 6 U1 0 U2 0 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD MAR 13 PY 2004 VL 363 IS 9412 BP 833 EP 834 DI 10.1016/S0140-6736(04)15770-X PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 803LB UT WOS:000220231500003 PM 15031022 ER PT J AU Sigurdson, AJ Hauptmann, M Chatterjee, N Alexander, BH Doody, MM Rutter, JL Struewing, JP AF Sigurdson, AJ Hauptmann, M Chatterjee, N Alexander, BH Doody, MM Rutter, JL Struewing, JP TI Kin-cohort estimates for familial breast cancer risk in relation to variants in DNA base excision repair, BRCA1 interacting and growth factor genes SO BMC CANCER LA English DT Article ID ACID SUBSTITUTION VARIANTS; ESTIMATING PENETRANCE; XRCC1; POLYMORPHISMS; SUSCEPTIBILITY; PREVALENCE; FREQUENCY; MUTATIONS; ADDUCTS; HUMANS AB Background: Subtle functional deficiencies in highly conserved DNA repair or growth regulatory processes resulting from polymorphic variation may increase genetic susceptibility to breast cancer. Polymorphisms in DNA repair genes can impact protein function leading to genomic instability facilitated by growth stimulation and increased cancer risk. Thus, 19 single nucleotide polymorphisms (SNPs) in eight genes involved in base excision repair (XRCC1, APEX, POLD1), BRCA1 protein interaction (BRIP1, ZNF350, BRCA2), and growth regulation (TGFbeta1, IGFBP3) were evaluated. Methods: Genomic DNA samples were used in Taqman 5'-nuclease assays for most SNPs. Breast cancer risk to ages 50 and 70 were estimated using the kin-cohort method in which genotypes of relatives are inferred based on the known genotype of the index subject and Mendelian inheritance patterns. Family cancer history data was collected from a series of genotyped breast cancer cases (N=748) identified within a cohort of female US radiologic technologists. Among 2,430 female first-degree relatives of cases, 190 breast cancers were reported. Results: Genotypes associated with increased risk were: XRCC1 R194W (WW and RW vs. RR, cumulative risk up to age 70, risk ratio (RR)=2.3; 95% CI 1.3-3.8); XRCC1 R399Q (QQ vs. RR, cumulative risk up to age 70, RR=1.9; 1.1-3.9); and BRIP1 (or BACH1) P919S (SS vs. PP, cumulative risk up to age 50, RR=6.9; 1.6-29.3). The risk for those heterozygous for BRCA2 N372H and APEX D148E were significantly lower than risks for homozygotes of either allele, and these were the only two results that remained significant after adjusting for multiple comparisons. No associations with breast cancer were observed for: APEX Q51H; XRCC1 R280H; IGFPB3-202A>C; TGFbeta1 L10P, P25R, and T2631; BRCA2 N289H and T1915M; BRIP1-64A>C; and ZNF350 (or ZBRK1) 1845C>T, L66P, R501S, and S472P. Conclusion: Some variants in genes within the base-excision repair pathway (XRCC1) and BRCA1 interacting proteins (BRIP1) may play a role as low penetrance breast cancer risk alleles. Previous association studies of breast cancer and BRCA2 N372H and functional observations for APEX D148E ran counter to our findings of decreased risks. Due to the many comparisons, cautious interpretation and replication of these relationships are warranted. C1 NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA. NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA. Univ Minnesota, Div Environm & Occupat Hlth, Minneapolis, MN 55455 USA. NCI, Lab Populat Genet, NIH, DHHS, Bethesda, MD 20892 USA. RP Sigurdson, AJ (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, 6120 Execut Blvd, Bethesda, MD 20892 USA. EM sigurdsa@mail.nih.gov; Hauptmam@mail.nih.gov; Chattern@mail.nih.gov; balex@umn.edu; doodym@mail.nih.gov; rutterj@mail.nih.gov; struewij@mail.nih.gov RI Struewing, Jeffery/C-3221-2008; Struewing, Jeffery/I-7502-2013 OI Struewing, Jeffery/0000-0002-4848-3334 NR 43 TC 56 Z9 61 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2407 J9 BMC CANCER JI BMC Cancer PD MAR 12 PY 2004 VL 4 AR 9 DI 10.1186/1471-2407-4-9 PG 12 WC Oncology SC Oncology GA 820SW UT WOS:000221410600001 PM 15113441 ER PT J AU Mitchum, RD Kiyatkin, EA AF Mitchum, RD Kiyatkin, EA TI Brain hyperthermia and temperature fluctuations during sexual interaction in female rats SO BRAIN RESEARCH LA English DT Article DE female sexual behavior; brain temperature; hyperthermia; neural activity; motivational arousal; medial preoptic area of hypothalamus; nucleus accumbens; rat ID MEDIAL PREOPTIC AREA; NUCLEUS-ACCUMBENS; RATTUS-NORVEGICUS; NEURONAL-ACTIVITY; BEHAVIOR; AROUSAL; HYPOTHALAMUS; STIMULATION; ACTIVATION AB Since the metabolic activity of neural cells is accompanied by heat release, brain temperature monitoring provides insight into behavior-associated changes in neural activity. In the present study, local temperatures Were continuously recorded in several brain structures (nucleus accumbens, medical-preoptic hypothalamus and hippocampus) and a non-locomotor head muscle (musculus temporalis) in a receptive female rat during sexually arousing stimulation and Subsequent copulatory behavior with an experienced male. Placement of the mate into a neighboring compartment increased the female's temperature (similar to 0.8 degreesC) and additional, transient increases (similar to 0.2 degreesC) occurred when the rats were allowed to see and smell each other through a transparent barrier. Temperatures gradually increased further as the male repeatedly mounted and achieved intromissions, peaked 2-3 min after male's ejaculation (0.2-0.4 degreesC), and abruptly dropped until the male initiated a new copulatory cycle. Similar biphasic fluctuations accompanied subsequent copulatory cycles. Although both arousal-related temperature increases and biphasic fluctuations associated with copulatory cycles were evident in each recording location, brain sites showed consistently faster and stronger increases than the muscle, suggesting metabolic brain activation as the primary source of brain temperature fluctuations and a force behind associated changes in brain temperature. Robust brain hyperthermia and the generally similar pattern of phasic temperature fluctuations associated with individual events of sexual interaction found in males and females suggest widespread neural activation (motivational arousal) as a driving force underlying this cooperative motivated behavior in animals of both sexes. Females, however, showed different temperature changes in association with the initial (first Mount or intromission) and final (ejaculation) events of each copulatory cycle, suggesting sex-specific differences in neural activity associated with the initiation and regulation Of Sexual behavior. Published by Elsevier B.V. C1 NIDA, Behav Neurosci Branch, Intramural Res Program, NIH,DHHS, Baltimore, MD 21224 USA. RP Kiyatkin, EA (reprint author), NIDA, Behav Neurosci Branch, Intramural Res Program, NIH,DHHS, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM ekiyatki@intra.nida.nih.gov NR 50 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD MAR 12 PY 2004 VL 1000 IS 1-2 BP 110 EP 122 DI 10.1016/j.brainres.2003.12.024 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 813DP UT WOS:000220888100014 PM 15053959 ER PT J AU Prybylowski, K Wenthold, RJ AF Prybylowski, K Wenthold, RJ TI N-methyl-D-aspartate receptors: Subunit assembly and trafficking to the synapse SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Review ID ER RETENTION SIGNAL; IONOTROPIC GLUTAMATE RECEPTORS; EXTRASYNAPTIC NMDA RECEPTORS; CELL-SURFACE EXPRESSION; PROTEIN-KINASE-C; POSTSYNAPTIC MEMBRANE; EXOCYST COMPLEX; MOLECULAR-BASIS; AMPA RECEPTORS; PSD-95 C1 NIDCD, Neurochem Lab, NIH, Bethesda, MD 20892 USA. RP Prybylowski, K (reprint author), NIDCD, Neurochem Lab, NIH, Bldg 50,Rm 4148, Bethesda, MD 20892 USA. EM prybylow@nidcd.nih.gov NR 60 TC 85 Z9 90 U1 1 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 12 PY 2004 VL 279 IS 11 BP 9673 EP 9676 DI 10.1074/jbc.R300029200 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 800TK UT WOS:000220050400001 PM 14742424 ER PT J AU Qiu, Y Guo, M Huang, SM Stein, R AF Qiu, Y Guo, M Huang, SM Stein, R TI Acetylation of the BETA2 transcription factor by p300-associated factor is important in insulin gene expression SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LOOP-HELIX PROTEINS; HOMEODOMAIN PROTEIN; DNA-BINDING; HISTONE ACETYLTRANSFERASES; ENHANCER ACTIVITY; P300 COACTIVATOR; MAMMALIAN-CELLS; FACTOR GATA-1; II GENE; DIFFERENTIATION AB The BETA2 transcription factor influences islet beta cell development and function. Activation of insulin gene transcription by this member of the basic helix-loop-elix gene family is mediated by p300 through the ability of this coactivator to form a functional bridge between the basal transcriptional apparatus, BETA2, and PDX-1, another key transcription factor. In this report, we examined whether BETA2-mediated stimulation was also directly influenced by the acetyltransferase activities of p300 or the p300-associated factor. BETA2 was specifically and selectively acetylated by p300-associated factor in beta cells. Sites of BETA2 acetylation were found within the loop region of the basic helix-loop-elix DNA binding/dimerization domain and a more C-erminal region involved in activation. Insulin gene transcription was decreased by blocking acetylation of BETA2 because of effects on DNA binding and activation potential. These findings suggest that acetylation of BETA2 plays a role in controlling the activation state of this islet regulatory factor. C1 Vanderbilt Univ, Med Ctr, Dept Physiol & Mol Biophys, Nashville, TN 37215 USA. NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Stein, R (reprint author), Vanderbilt Univ, Med Ctr, Dept Physiol & Mol Biophys, Nashville, TN 37215 USA. EM roland.stein@mcmail.vanderbilt.edu FU NIDDK NIH HHS [P60 DK20593, R01 DK 50203, R01 DK55091] NR 66 TC 24 Z9 30 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 12 PY 2004 VL 279 IS 11 BP 9796 EP 9802 DI 10.1074/jbc.M307577200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 800TK UT WOS:000220050400018 PM 14701848 ER PT J AU Sharma, S Sommers, JA Wu, L Bohr, VA Hickson, ID Brosh, RM AF Sharma, S Sommers, JA Wu, L Bohr, VA Hickson, ID Brosh, RM TI Stimulation of flap endonuclease-1 by the Bloom's syndrome protein SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SYNDROME GENE-PRODUCT; OKAZAKI FRAGMENT MATURATION; ROTHMUND-THOMSON-SYNDROME; TOPOISOMERASE-III-ALPHA; WERNER-SYNDROME PROTEIN; SACCHAROMYCES-CEREVISIAE; SYNDROME HELICASE; DNA-REPLICATION; HOMOLOGOUS RECOMBINATION; MUTATION AVOIDANCE AB Bloom's syndrome (BS) is a rare autosomal recessive genetic disorder associated with genomic instability and an elevated risk of cancer. Cellular features of BS include an accumulation of abnormal replication intermediates and increased sister chromatid exchange. Although it has been suggested that the underlying defect responsible for hyper-recombination in BS cells is a temporal delay in the maturation of DNA replication intermediates, the precise role of the BS gene product, BLM, in DNA metabolism remains elusive. We report here a novel interaction of the BLM protein with the human 5'-flap endonuclease/5'-3' exonuclease (FEN-1), a genome stability factor involved in Okazaki fragment processing and DNA repair. BLM protein stimulates both the endonucleolytic and exonucleolytic cleavage activity of FEN-1 and this functional interaction is independent of BLM catalytic activity. BLM and FEN-1 are associated with each other in human nuclei as shown by their reciprocal co-immunoprecipitation from HeLa nuclear extracts. The BLM-FEN-1 physical interaction is mediated through a region of the BLM C-terminal domain that shares homology with the FEN-1 interaction domain of the Werner syndrome protein, a RecQ helicase family member homologous to BLM. This study provides the first evidence for a direct interaction of BLM with a human nucleolytic enzyme. We suggest that functional interactions between RecQ helicases and Rad2 family nucleases serve to process DNA substrates that are intermediates in DNA replication and repair. C1 NIA, Lab Mol Gerontol, NIH, DHHS, Baltimore, MD 21224 USA. Univ Oxford, Weatherall Inst Mol Med, Canc Res UK Labs, John Radcliffe Hosp, Oxford OX3 9DS, England. Univ Hyderabad, Sch Life Sci, Dept Biochem, Hyderabad 500046, Andhra Pradesh, India. RP Brosh, RM (reprint author), NIA, Lab Mol Gerontol, NIH, DHHS, Baltimore, MD 21224 USA. EM BroshR@grc.nia.gov OI Sharma, Sudha/0000-0003-2765-2482 NR 66 TC 65 Z9 68 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 12 PY 2004 VL 279 IS 11 BP 9847 EP 9856 DI 10.1074/jbc.M309898200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 800TK UT WOS:000220050400024 PM 14688284 ER PT J AU Del Carpio, RV Gonzalez-Nilo, FD Jayaram, H Spencer, E Prasad, BVV Patton, JT Taraporewala, ZF AF Del Carpio, RV Gonzalez-Nilo, FD Jayaram, H Spencer, E Prasad, BVV Patton, JT Taraporewala, ZF TI Role of the histidine triad-like motif in nucleotide hydrolysis by the rotavirus RNA-packaging protein NSP2 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TEMPERATURE-SENSITIVE MUTANTS; VIRUS NONSTRUCTURAL PROTEIN; CASEIN KINASE-II; IN-VIVO; SIMIAN ROTAVIRUS-SA11; PHOSPHOPROTEIN NSP5; BINDING ACTIVITY; PHOSPHORYLATION; LOCALIZATION; MULTIMERS AB Octamers formed by the nonstructural protein NSP2 of rotavirus are proposed to function as molecular motors in the packaging of the segmented double-stranded RNA genome. The octamers have RNA binding, helix unwinding, and Mg2+-dependent NTPase activities and play a crucial role in assembly of viral replication factories (viroplasms). Comparison of x-ray structures has revealed significant structural homology between NSP2 and the histidine triad ( HIT) family of nucleotidyl hydrolases, which in turn has suggested the location of the active site for NTP hydrolysis in NSP2. Consistent with the structural predictions, we show here using site-specific mutagenesis and ATP docking simulations that the active site for NTP hydrolysis is localized to residues within a 25-Angstrom-deep cleft between the C- and N-terminal domains of the NSP2 monomer. Although lacking the precise signature HIT motif (HOHOHOO where O is a hydrophobic residue), our analyses demonstrate that histidines (His(221) and His(225)) represent critical residues of the active site. Similar to events occurring during nucleotide hydrolysis by HIT proteins, NTP hydrolysis by NSP2 was found to produce a short lived phosphorylated intermediate. Evaluation of the biological importance of the NTPase activity of NSP2 by transient expression in mammalian cells showed that such activity has no impact on the ability of NSP2 to induce the hyperphosphorylation of NSP5 or to interact with NSP5 to form viroplasm-like structures. Hence the NTPase activity of NSP2 probably has a role subsequent to the formation of viroplasms, consistent with its suspected involvement in RNA packaging and/or replication. C1 NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. Baylor Coll Med, Verna & Marrs McLean Dept Biochem & Mol Biol, Houston, TX 77030 USA. Univ Santiago Chile, Fac Quim & Biol, Dept Ciencias Quim, Santiago, Chile. Univ Santiago Chile, Virol Lab, Santiago, Chile. RP Taraporewala, ZF (reprint author), NIAID, Infect Dis Lab, NIH, 50 South Dr,MSC 8026,Rm 6314, Bethesda, MD 20892 USA. EM ztarapore@niaid.nih.gov RI Patton, John/P-1390-2014; Gonzalez-Nilo, Fernando/M-5671-2016 OI Gonzalez-Nilo, Fernando/0000-0001-6857-3575 NR 38 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 12 PY 2004 VL 279 IS 11 BP 10624 EP 10633 DI 10.1074/jbc.M311563200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 800TK UT WOS:000220050400116 ER PT J AU Roll-Mecak, A Alone, P Cao, CN Dever, TE Burley, SK AF Roll-Mecak, A Alone, P Cao, CN Dever, TE Burley, SK TI X-ray structure of translation initiation factor eIF2 gamma - Implications for tRNA and eIF2 alpha binding SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CRYSTAL-STRUCTURE; EF-TU; ANOMALOUS DIFFRACTION; SUBUNIT; YEAST; GCN4; COMPLEX; INSIGHTS; REVEALS; SITE AB The x-ray structure of the gamma-subunit of the heterotrimeric translation initiation factor eIF2 has been determined to 2.4-Angstrom resolution. eIF2 is a GTPase that delivers the initiator Met-tRNA to the P site on the small ribosomal subunit during a rate-limiting initiation step in translation. The structure of eIF2gamma closely resembles that of EF1A . GTP, consisting of an N-terminal G domain followed by two beta-barrels arranged in a closed configuration with domain II packed against the G domain in the vicinity of the Switch regions. The G domain of eIF2gamma has an unusual zinc ribbon motif, not previously found in other GTPases. Structure-based site-directed mutagenesis was used to identify two adjacent features on the surface of eIF2gamma that bind the alpha-subunit and Met-tRNA(i)(Met), respectively. These structural, biochemical, and genetic results provide new insights into eIF2 ternary complex assembly. C1 Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10021 USA. Rockefeller Univ, Labs Mol Biophys, New York, NY 10021 USA. NICHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. RP Burley, SK (reprint author), Struct GenomiX Inc, 10505 Roselle St, San Diego, CA 92121 USA. EM stephen_burley@stromix.com OI Dever, Thomas/0000-0001-7120-9678 FU NIGMS NIH HHS [GM61262] NR 35 TC 46 Z9 50 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 12 PY 2004 VL 279 IS 11 BP 10634 EP 10642 DI 10.1074/jbc.M310418200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 800TK UT WOS:000220050400117 PM 14688270 ER PT J AU Lin, Y Choksi, S Shen, HM Yang, QF Hur, GM Kim, YS Tran, JH Nedospasov, SA Liu, ZG AF Lin, Y Choksi, S Shen, HM Yang, QF Hur, GM Kim, YS Tran, JH Nedospasov, SA Liu, ZG TI Tumor necrosis factor-induced nonapoptotic cell death requires receptor-interacting protein-mediated cellular reactive oxygen species accumulation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NF-KAPPA-B; DOMAIN KINASE RIP; SIGNAL-TRANSDUCTION; INDUCED APOPTOSIS; TERMINAL KINASE; JNK ACTIVATION; TNF; PATHWAY; TRAF2; CYTOTOXICITY AB The mechanism of tumor necrosis factor (TNF)-induced nonapoptotic cell death is largely unknown, although the mechanism of TNF-induced apoptosis has been studied extensively. In wild-type mouse embryonic fibroblast cells under a caspase-inhibited condition, TNF effectively induced cell death that morphologically resembled necrosis. In this study, we utilized gene knockout mouse embryonic fibroblasts cells and found that tumor necrosis factor receptor ( TNFR) I mediates TNF-induced necrotic cell death, and that RIP, FADD, and TRAF2 are critical components of the signaling cascade of this TNF-induced necrotic cell death. Inhibitors of NF-kappaB facilitated TNF-induced necrotic cell death, suggesting that NF-kappaB suppresses the necrotic cell death pathway. JNK, p38, and ERK activation seem not to be required for this type of cell death because mitogen-activated protein kinase inhibitors did not significantly affect TNF-induced necrotic cell death. In agreement with the previous reports that the reactive oxygen species (ROS) may play an important role in this type of cell death, the ROS scavenger butylated hydroxyanisole efficiently blocked TNF-induced necrotic cell death. Interestingly, during TNF-induced necrotic cell death, the cellular ROS level was significantly elevated in wild type, but not in RIP-/-, TRAF2(-/-), and FADD(-/-) cells. These results suggest that RIP, TRAF2, and FADD are crucial in mediating ROS accumulation in TNF-induced necrotic cell death. C1 NCI, Cell & Canc Biol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Basic Res Program, Sci Applicat Int Corp, LMI,CCR,NIH, Frederick, MD 21702 USA. RP Lin, Y (reprint author), NCI, Cell & Canc Biol Branch, Ctr Canc Res, NIH, Bldg 10,Rm 6N105,9000 Rockville Pike, Bethesda, MD 20892 USA. EM linyo@mail.nih.gov RI SHEN, Han-Ming/B-5942-2011; Nedospasov, Sergei/J-5936-2013; Nedospasov, Sergei/L-1990-2015; Nedospasov, Sergei/Q-7319-2016 OI SHEN, Han-Ming/0000-0001-7369-5227; NR 47 TC 248 Z9 255 U1 3 U2 13 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 12 PY 2004 VL 279 IS 11 BP 10822 EP 10828 DI 10.1074/jbc.M313141200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 800TK UT WOS:000220050400138 PM 14701813 ER PT J AU Tolstorukov, MY Jernigan, RL Zhurkin, VB AF Tolstorukov, MY Jernigan, RL Zhurkin, VB TI Protein-DNA hydrophobic recognition in the minor groove is facilitated by sugar switching SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE protein-DNA recognition; DNA deformability; hydrophobic interactions; sugar pucker; DNA accessible surface ID CRYSTAL-STRUCTURE; B-DNA; NUCLEIC-ACIDS; GLOBULAR-PROTEINS; STRUCTURAL BASIS; SEX REVERSAL; DOUBLE HELIX; TATA-BOX; SEQUENCE; TRANSITION AB Information readout in the DNA minor groove is accompanied by substantial DNA deformations, such as sugar switching between the two conformational domains, B-like C2'-endo and A-like C3'-endo. The effect of sugar puckering on the sequence-dependent protein-DNA interactions has not been studied systematically, however. Here, we analyzed the structural role of A-like nucleotides in 156 protein-DNA complexes solved by X-ray crystallography and NMR. To this end, a new algorithm was developed to distinguish interactions in the minor groove from those in the major groove, and to calculate the solvent-accessible surface, areas in each groove separately. Based on this approach, we found a striking difference between the sets of amino acids interacting with B-like and A-like nucleotides in the minor groove. Polar amino acids mostly interact with B-nucleotides, while hydrophobic amino acids interact extensively with A-nucleotides (a hydrophobicity-structure correlation). This tendency is consistent with the larger exposure of hydrophobic surfaces in the case of A-like sugars. Overall, the A-like nucleotides aid in achieving protein-induced fit in two major ways. First, hydrophobic clusters formed by several consecutive A-like sugars interact cooperatively with the non-polar surfaces in proteins. Second, the sugar switching occurs in large kinks promoted by direct protein contact, predominantly at the pyrimidine-purine dimeric steps. The sequence preference for the B-to-A sugar repuckering, observed for pyrimidines, suggests that the described DNA deformations contribute to specificity of the protein-DNA recognition in the minor groove. Published by Elsevier Ltd. C1 NCI, Lab Expt & Computat Biol, NIH, Bethesda, MD 20892 USA. Iowa State Univ, Laurence H Baker Ctr Bioinformat & Biol Stat, Ames, IA 50011 USA. RP Zhurkin, VB (reprint author), NCI, Lab Expt & Computat Biol, NIH, Bg 12B,Rm B116, Bethesda, MD 20892 USA. EM zhurkin@nih.gov RI Jernigan, Robert/A-5421-2012 NR 64 TC 47 Z9 51 U1 0 U2 8 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD MAR 12 PY 2004 VL 337 IS 1 BP 65 EP 76 DI 10.1016/j.jmb.2004.01.011 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 800TT UT WOS:000220051300005 PM 15001352 ER PT J AU Ling, H Boudsocq, F Woodgate, R Yang, W AF Ling, H Boudsocq, F Woodgate, R Yang, W TI Snapshots of replication through an abasic lesion: Structural basis for base substitutions and frameshifts SO MOLECULAR CELL LA English DT Article ID FAMILY DNA-POLYMERASE; CRYSTAL-STRUCTURE; ESCHERICHIA-COLI; ERROR-PRONE; SULFOLOBUS-SOLFATARICUS; DIOL EPOXIDE; Y-FAMILY; BYPASS; FIDELITY; MECHANISM AB Dpo4 from S. Solfataricus, a DinB-like Y family polymerase, efficiently replicates DNA past an abasic lesion. We have determined crystal structures of Dpo4 complexed with five different abasic site-containing DNA substrates and find that translesion synthesis is template directed with the abasic site looped out and the incoming nucleotide is opposite the base 5' to the lesion. The ensuing DNA synthesis generates a -1 frameshift when the abasic site remains extrahelical. Template realignment during primer extension is also observed, resulting in base substitutions or even +1 frameshifts. In the case of a +1 frameshift, the extra nucleotide is accommodated in the solvent-exposed minor groove. In addition, the structure of an unproductive Dpo4 ternary complex suggests that the flexible little finger domain facilitates DNA orientation and translocation during translesion synthesis. C1 NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NICHHD, Lab Genom Integrit, NIH, Bethesda, MD 20892 USA. RP Yang, W (reprint author), NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. EM wei.yang@nih.gov RI Ling, Hong/E-3729-2010; Yang, Wei/D-4926-2011 OI Yang, Wei/0000-0002-3591-2195 NR 46 TC 136 Z9 137 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD MAR 12 PY 2004 VL 13 IS 5 BP 751 EP 762 DI 10.1016/S1097-2765(04)00101-7 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 803CK UT WOS:000220209000012 PM 15023344 ER PT J AU Hori, H Nagasawa, H Uto, Y Ohkura, K Kirk, KL Uehara, Y Shimamura, M AF Hori, H Nagasawa, H Uto, Y Ohkura, K Kirk, KL Uehara, Y Shimamura, M TI Design of hypoxia-targeting protein tyrosine kinase inhibitor using an innovative pharmacophore 2-methylene-4-cyclopentene-1,3-dione SO BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS LA English DT Article; Proceedings Paper CT 3rd International Conference on Inhibitors of Protein Kinases (IPK 2003) CY 2003 CL Warsaw, POLAND DE antitumor agent; protein tyrosine kinase inhibitor; tyrphostin AG17; TX-1123; mitochondrial toxicity; hypoxia-targeting PTK inhibitor; 2-methylene4-cyclopentene-1,3-dione ID EHRLICH ASCITES-CARCINOMA; GROWTH-FACTOR-RECEPTOR; INTRATUMOR QUIESCENT CELLS; AG17 INDUCES APOPTOSIS; BIOLOGICAL-ACTIVITIES; TYRPHOSTIN AG17; CANCER-THERAPY; ANTIPROLIFERATIVE AGENTS; RADIOSENSITIZER KIN-806; SIGNAL-TRANSDUCTION AB We review in this report our strategy and tactics for the design of 2-hydroxyarylidene-4-cyclopentene-1,3-diones as protein tyrosine kinase (PTK) inhibitors having low mitochondrial toxicities and/or hypoxia-targeting function. We based our synthetic design on an innovative pharmacophore, 2-methylene-4-cyclopentene-1,3-dione. We first showed the effectiveness of this pharmacophore in the development of 2-methylene-4-cyclopentene-1,3-dione as PTK inhibitor that have lower mitochondrial toxicity than the potent PTK inhibitor tyrphostin AG17 Our results show that the cyclopentenedione-derived TX-1123 is a more potent antitumor tyiphostin and also shows lower mitochondrial toxicity than the malononitrile-derived AG17 The O-methylation product of TX-1123 (TX-1925) retained its tyrphostin-like properties. including mitochondrial toxicity and antitumor activities. However, the methylation product of AG17 (TX-1927) retained its tyrphostin-like antitumor activities, but lost its mitochondrial toxicity. Our comprehensive evaluation of these agents with respect to PTK inhibition, mitochondrial inhibition, antitumor activity, and hepatotoxicity demonstrates thatPTK inhibitors TX-1123 and TX-1925 are more promising candidates for antitumor agents than tyrphostin AGIT Secondly, as a further investigation of the promising power of this 4-cyclopentene-1,3-dione as an innovative pharmacophore, we discuss our strategy of development of hypoxia-targeting PTK inhibitor TX1123 analogues. 2 -nitroimidazole-aminomethylenecyclopentenediones, such as TX-2036, for cancer treatment, especially for pancreatic cancers, which have a high level of hypoxia. (C) 2003 Elsevier B.V. All rights reserved. C1 Univ Tokushima, Fac Engn, Dept Biol Sci & Technol, Tokushima 7708506, Japan. Nagoya Univ, Grad Sch Bioagr Sci, Chikusa Ku, Aichi 4648601, Japan. NIDDKD, Lab Bioorgan Chem, NIH, Bethesda, MD 20892 USA. Natl Inst Infect Dis, Dept Bioact Mol, Shinjuku Ku, Tokyo 1628640, Japan. Tokyo Metropolitan Inst Med Sci, Med R&D Ctr, Bunkyo Ku, Tokyo 1138613, Japan. RP Hori, H (reprint author), Univ Tokushima, Fac Engn, Dept Biol Sci & Technol, Minamijosanjimacho 2, Tokushima 7708506, Japan. EM hori@bio.tokushima-u.ac.jp NR 75 TC 12 Z9 13 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-9639 J9 BBA-PROTEINS PROTEOM JI BBA-Proteins Proteomics PD MAR 11 PY 2004 VL 1697 IS 1-2 SI SI BP 29 EP 38 DI 10.1016/j.bbapap.2003.11.011 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 806PT UT WOS:000220446500004 PM 15023348 ER PT J AU Cho-Chung, YS AF Cho-Chung, YS TI Antisense protein kinase A RI alpha-induced tumor reversion: portrait of a microarray SO BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS LA English DT Article; Proceedings Paper CT 3rd International Conference on Inhibitors of Protein Kinases (IPK 2003) CY 2003 CL Warsaw, POLAND DE antisense; cancer chemotherapy; DNA microarray; gene expression; growth inhibition; oligonucleotide; protein kinase A ID MIXED-BACKBONE OLIGONUCLEOTIDES; RII(BETA) REGULATORY SUBUNIT; MAMMARY EPITHELIAL-CELLS; FIBROBLAST-GROWTH-FACTOR; BREAST-CANCER CELLS; GENE-EXPRESSION; IN-VIVO; DOWN-REGULATION; HL-60 LEUKEMIA; MESSENGER-RNA AB Antisense oligonucleotides can selectively block disease-causing genes due to the specificity of the Watson-Crick base-pairing mechanism of action. A genome-wide view of antisense technology is illustrated via protein kinase A RIalpha antisense. Complementary DNA microarray analysis of the Met antisense-induced expression profile shows the up- and down-regulation of clusters of coordinately expressed genes that define the molecular portrait of a reverted tumor cell phenotype. This global view broadens the horizons of antisense technology; it advances the promise of antisense beyond a single target gene to the whole cell and the whole organism. Along with recent rapid advances in oligonucleotide tech no logies-including new chemical and biological understanding of more sophisticated nucleic acid drugsoligonucleotide-based iene silencing offers not only an exquisitely specific genetic tool for exploring basic science but also an exciting possibility for treating and preventing cancer and other diseases. (C) 2003 Elsevier B.V. All rights reserved. C1 NCI, Ctr Canc Res, Basic Res Lab, Cellular Biochem Sect, Bethesda, MD 20892 USA. RP Cho-Chung, YS (reprint author), NCI, Ctr Canc Res, Basic Res Lab, Cellular Biochem Sect, Bldg 10,Room 5B05,9000 Rockville Pike, Bethesda, MD 20892 USA. EM yc12b@nih.gov FU NCI NIH HHS [N02-BC76212/C2700212] NR 61 TC 17 Z9 17 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-9639 J9 BBA-PROTEINS PROTEOM JI BBA-Proteins Proteomics PD MAR 11 PY 2004 VL 1697 IS 1-2 SI SI BP 71 EP 79 DI 10.1016/j.bbapap.2003.11.014 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 806PT UT WOS:000220446500007 PM 15023351 ER PT J AU Kesavapany, S Li, BS Amin, N Zheng, YL Grant, P Pant, HC AF Kesavapany, S Li, BS Amin, N Zheng, YL Grant, P Pant, HC TI Neuronal cyclin-dependent kinase 5: role in nervous system function and its specific inhibition by the Cdk5 inhibitory peptide SO BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS LA English DT Article; Proceedings Paper CT 3rd International Conference on Inhibitors of Protein Kinases (IPK 2003) CY 2003 CL Warsaw, POLAND DE Cdk5; p35; CIP; phosphorylation; tau; Alzheimer's disease; signal transduction ID MYELIN-ASSOCIATED GLYCOPROTEIN; WEIGHT NEUROFILAMENT PROTEIN; SYNAPTIC VESICLE ENDOCYTOSIS; GLIAL CYTOPLASMIC INCLUSIONS; TANDEM MASS-SPECTROMETRY; REGULATORY SUBUNIT P35; PHOSPHORYLATION SITES; NEURITE OUTGROWTH; ACTIVATOR P35; IN-VIVO AB Cyclin-dependent kinase 5 (Cdk5) is a member of the cyclin-dependent kinase family that is involved in the regulation of the cell cycle. As their name suggests, the Cdks require association with activator proteins called cyclins for their activity. Cdk5, however, is unique to this family of proline-directed serine/threonine kinases on two accounts. Firstly, Cdk5 has not been found to function in the cell cycle and, although expressed in a number of tissues, its activity is restricted to the nervous system. Secondly, unlike the other members of the Cdk family, Cdk5 is not activated by association with a cyclin, although it can bind them. Instead, Cdk5 is activated by the activator proteins p35 and p39 that are structurally distinct from cyclins and have, for the most part, a neuronal-specific expression pattern. In the past decade of research on Cdk5, it is now established that Cdk5 activity is critical for the proper formation and function of the brain. Moreover, its role as a central kinase, phosphorylating its substrates in its 'cross-talk' control of other kinase and signal transduction pathways, has also been determined. In addition to the normal physiological role of Cdk5, the kinase has been implicated in certain neurodegenerative disorders. For example, Cdk5 associates with the proteolytic, more active p25 fragment that is derived through the cleavage of p35. In turn, the p25/Cdk5 complex aberrantly phosphorylates its substrates tau and neurofilaments, which has been implicated in the pathogenesis of these disorders. Here, we attempt to review the past decade of research on Cdk5 from our laboratory and others, on the roles of Cdk5 in nervous system function. Additionally, our research has recently uncovered a possible therapeutic avenue of research, focusing on inhibition of aberrant Cdk5 hyperactivity which may well be used to treat the symptoms of a number of neurodegenerative diseases. The elucidation of a specific inhibitor of p25/Cdk5, termed CIP, also inhibits p25/Cdk5-mediated tau phosphorylation. This may well provide us with avenues of research focusing on the inhibition of pathologically damaging p25/Cdk5 species. (C) 2003 Elsevier B.V. All rights reserved. C1 NINDS, Lab Neurochem, NIH, Bethesda, MD 20892 USA. RP Pant, HC (reprint author), NINDS, Lab Neurochem, NIH, Bldg 36,Room 4D-28, Bethesda, MD 20892 USA. EM panth@ninds.nih.gov NR 120 TC 46 Z9 50 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-9639 J9 BBA-PROTEINS PROTEOM JI BBA-Proteins Proteomics PD MAR 11 PY 2004 VL 1697 IS 1-2 SI SI BP 143 EP 153 DI 10.1016/j.bbapap.2003.11.020 PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 806PT UT WOS:000220446500013 PM 15023357 ER PT J AU Ananthan, S Khare, NK Saini, SK Seitz, LE Bartlett, JL Davis, P Dersch, CM Porreca, F Rothman, RB Bilsky, EJ AF Ananthan, S Khare, NK Saini, SK Seitz, LE Bartlett, JL Davis, P Dersch, CM Porreca, F Rothman, RB Bilsky, EJ TI Identification of opioid ligands possessing mixed mu agonist/delta antagonist activity among pyridomorphinans derived from naloxone, oxymorphone, and hydropmorphone SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID MORPHINE-TOLERANCE; RECEPTOR-BINDING; ANTINOCICEPTIVE TOLERANCE; PHYSICAL-DEPENDENCE; AFFINITY; MICE; NALTRINDOLE; EFFICACY; ANALOGS; OLIGOMERIZATION AB A series of pyridomorphinans derived from naloxone, oxymorphone, and hydromorphone (7a-k) were synthesized and evaluated for binding affinity at the opioid delta, mu, and kappa receptors in brain membranes using radioligand binding assays and for functional activity in vitro using [S-35] GTP-gamma-S binding assays in brain tissues and bioassays using guinea pig ileum (GPI) and mouse vas deferens (MVD) smooth muscle preparations. The pyridine ring unsubstituted pyridomorphinans possessing the oxymorphone and hydromorphone framework displayed nearly equal binding affinity at the mu and delta receptors. Their affinities at the K site were nearly 10-fold less than their binding affinities at the mu and delta sites. Introduction of aryl substituents at the 5'-position on the pyridine ring improved the binding affinity at the delta site while decreasing the binding affinity at the mu site. Nearly all of the ligands possessing an N-methyl group at the 17-position with or without a hydroxyl group at the 14-position of the morphinan moiety displayed agonist activity at the u receptor with varying potencies and efficacies. In the [S-35] GTP-gamma-S binding assays, most of these pyridomorphinans were devoid of any significant agonist activity at the delta and kappa receptors but displayed moderate to potent antagonist activity at the delta receptors. In antinociceptive evaluations using the warm-water tall-withdrawal assay in mice, the pyridomorphinans produced analgesic effects with varying potencies and efficacies when administered by the intracerebroventricular route. Among the ligands studied, the hydromorphone-derived 4-chlorophenylpyridomorphinan 7h was identified as a ligand possessing a promising profile of mixed mu agonist/delta antagonist activity in vitro and in vivo. In a repeated administration paradigm in which the standard mu agonist morphine produces significant tolerance, repeated administration of the mu agonist/delta antagonist ligand 7h produced no tolerance. These results indicate that appropriate molecular manipulations of the morphinan templates could provide ligands with mixed mu agonist/delta antagonist profiles and such ligands may have the potential of emerging as novel analgesic drugs devoid of tolerance, dependence, and related side effects. C1 So Res Inst, Dept Organ Chem, Birmingham, AL 35255 USA. Natl Inst Drug Abuse, Clin Psychopharmacol Sect, IRP, Baltimore, MD 21224 USA. Univ Arizona, Dept Pharmacol, Coll Med, Hlth Sci Ctr, Tucson, AZ 85724 USA. Univ New England, Coll Osteopath Med, Dept Pharmacol, Biddeford, ME 04005 USA. RP Ananthan, S (reprint author), So Res Inst, Dept Organ Chem, Birmingham, AL 35255 USA. EM ananthan@sri.org FU NIDA NIH HHS [DA08883] NR 45 TC 38 Z9 40 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD MAR 11 PY 2004 VL 47 IS 6 BP 1400 EP 1412 DI 10.1021/jm030311v PG 13 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 800OX UT WOS:000220038700012 PM 14998329 ER PT J AU Earl, PL Americo, JL Wyatt, LS Eller, LA Whitbeck, JC Cohen, GH Eisenberg, RJ Hartmann, CJ Jackson, DL Kulesh, DA Martinez, MJ Miller, DM Mucker, EM Shamblin, JD Zwiers, SH Huggins, JW Jahrling, PB Moss, B AF Earl, PL Americo, JL Wyatt, LS Eller, LA Whitbeck, JC Cohen, GH Eisenberg, RJ Hartmann, CJ Jackson, DL Kulesh, DA Martinez, MJ Miller, DM Mucker, EM Shamblin, JD Zwiers, SH Huggins, JW Jahrling, PB Moss, B TI Immunogenicity of a highly attenuated MVA smallpox vaccine and protection against monkeypox SO NATURE LA English DT Article ID VIRUS PROPAGATION; STRAIN MVA; PROTEIN; NEUTRALIZATION; IMMUNIZATION; ANTIBODIES; CHALLENGE; INFECTION; VARIOLA; VECTOR AB The potential use of smallpox as a biological weapon has led to the production and stockpiling of smallpox vaccine and the immunization of some healthcare workers. Another public health goal is the licensing of a safer vaccine that could benefit the millions of people advised not to take the current one because they or their contacts have increased susceptibility to severe vaccine side effects(1). As vaccines can no longer be tested for their ability to prevent smallpox, licensing will necessarily include comparative immunogenicity and protection studies in non-human primates. Here we compare the highly attenuated modified vaccinia virus Ankara (MVA)(2) with the licensed Dryvax vaccine in a monkey model. After two doses of MVA or one dose of MVA followed by Dryvax, antibody binding and neutralizing titres and T-cell responses were equivalent or higher than those induced by Dryvax alone. After challenge with monkeypox virus, unimmunized animals developed more than 500 pustular skin lesions and became gravely ill or died, whereas vaccinated animals were healthy and asymptomatic, except for a small number of transient skin lesions in animals immunized only with MVA. C1 NIAID, NIH, Bethesda, MD 20892 USA. Henry M Jackson Fdn, Rockville, MD 20850 USA. Univ Penn, Sch Dent, Philadelphia, PA 19104 USA. Univ Penn, Sch Vet Med, Philadelphia, PA 19104 USA. USA, Med Res Inst Infect Dis, Frederick, MD 21702 USA. RP Moss, B (reprint author), NIAID, NIH, Bethesda, MD 20892 USA. EM bmoss@nih.gov NR 30 TC 219 Z9 224 U1 1 U2 10 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAR 11 PY 2004 VL 428 IS 6979 BP 182 EP 185 DI 10.1038/nature02331 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 801NW UT WOS:000220103600049 PM 15014500 ER PT J AU Hildesheim, J Belova, GI Tyner, SD Zhou, XW Vardanian, L Fornace, AJ AF Hildesheim, J Belova, GI Tyner, SD Zhou, XW Vardanian, L Fornace, AJ TI Gadd45a regulates matrix metalloproteinases by suppressing Delta Np63 alpha and beta-catenin via p38 MAP kinase and APC complex activation SO ONCOGENE LA English DT Article DE Gadd45a; beta-catenin; Delta Np63 alpha; keratinocyte; UV ID SQUAMOUS-CELL CARCINOMAS; TUMOR PROGRESSION; P63 EXPRESSION; SKIN-CANCER; P53 HOMOLOG; CYCLIN D1; APOPTOSIS; MATRILYSIN; PHOSPHORYLATION; PATHWAY AB The p53-regulated growth arrest and DNA damage-inducible gene product Gadd45a has been recently identified as a key factor protecting the epidermis against ultraviolet radiation (UVR)-induced skin tumors by activating p53 via the stress mitogen-activated protein kinase ( MAPK) signaling pathway. Herein we identify Gadd45a as an important negative regulator of two oncogenes commonly over-expressed in epithelial tumors: the p53 homologue DeltaNp63alpha and beta-catenin. DeltaNp63alpha is one of the several p63 isoforms and is the predominant species expressed in basal epidermal keratinocytes. DeltaNp63alpha lacks the N-terminal transactivation domain and behaves as a dominant-negative factor blocking expression of several p53-effector genes. DeltaNp63alpha also associates with and blocks activation of the adenomatous polyposis coli (APC) destruction complex that targets free cytoplasmic beta-catenin for degradation. While most beta-catenin protein is localized to the cell membrane and is involved in cell-cell adhesion, accumulation of free cytoplasmic beta-catenin will translocate into the nucleus where it functions in a bipartite transcription factor complex, whose targets include invasion and metastasis promoting endopeptidases, matrix metalloproteinases (MMP). We show that Gadd45a not only directly associates with two components of the APC complex, namely protein phosphatase 2A (PP2A) and glycogen synthase kinase 3beta (GSK3beta) but also promotes GSK3b dephosphorylation at Ser9, which is essential for GSK3b activation, and resultant activation of the APC destruction complex. We demonstrate that lack of Gadd45a not only prevents DeltaNp63alpha suppression and GSK3b dephosphorylation but also prevents free cytoplasmic beta-catenin degradation after UV irradiation. The inability of Gadd45a-null keratinocytes to suppress beta-catenin may contribute to the resulting observation of increased MMP expression and activity along with significantly faster keratinocyte migration in Matrigel in vitro and accelerated wound closure in vivo. Furthermore, epidermal keratinocytes treated with p38 MAPK inhibitors, both in vivo and in vitro, behave very similarly to Gadd45a-null keratinocytes after UVR. Similarly, Trp53-null mice are unable to attenuate DeltaNp63alpha expression in epidermal keratinocytes after such stress. These findings demonstrate a dependence on Gadd45a-mediated p38 MAPK and p53 activation for proper modulation of DeltaNp63alpha, GSK3beta, and beta-catenin after irradiation. Taken together, our results indicate that Gadd45a is able to repress DeltaNp63alpha, beta-catenin, and consequently MMP expression by two means: by maintaining UVR-induced p38 MAPK and p53 activation and also by associating with the APC complex. This implicates Gadd45a in the negative regulation of cell migration, and invasion. C1 NCI, Gene Response Sect, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Fornace, AJ (reprint author), NCI, Gene Response Sect, Ctr Canc Res, NIH, Bldg 37,Rm 6144,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. EM af6z@nih.gov RI Fornace, Albert/A-7407-2008 OI Fornace, Albert/0000-0001-9695-085X NR 50 TC 43 Z9 44 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAR 11 PY 2004 VL 23 IS 10 BP 1829 EP 1837 DI 10.1038/sj.onc.1207301 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 801XV UT WOS:000220129500004 PM 14647429 ER PT J AU Justus, BL Falkenstein, P Huston, AL Plazas, MC Ning, H Miller, RW AF Justus, BL Falkenstein, P Huston, AL Plazas, MC Ning, H Miller, RW TI Gated fiber-optic-coupled detector for in vivo real-time radiation dosimetry SO APPLIED OPTICS LA English DT Article ID PLASTIC SCINTILLATION DETECTORS; ENERGY BEAM DOSIMETRY; THEORETICAL CONSIDERATIONS; PHYSICAL CHARACTERISTICS; INDUCED LIGHT; SYSTEM AB Gated detection of the output of a fiber-optic-coupled radiation dosimeter effectively eliminated the direct contribution of Cerenkov radiation to the signal. The radiation source was an external beam radiotherapy machine that provided pulses of 6-MeV x rays. Gated detection was used to discriminate the signal collected during the radiation pulses, including Cerenkov interference, from the signal collected between the radiation pulses due only to phosphorescence from the Cu1+-doped glass detector. Gated detection of the long-lived phosphorescence of the Cu1+-doped glass provided real-time dose measurements that were linear with the absorbed dose and that were accurate for all field sizes studied. (C) 2004 Optical Society of America. C1 USN, Res Lab, Opt Sci Div, Washington, DC 20375 USA. SFA Inc, Largo, MD 20774 USA. NCI, Radiat Oncol Branch, Bethesda, MD 20784 USA. Univ Nacl Colombia, Fac Ciencias, Dept Fis, Bogota, Colombia. RP Justus, BL (reprint author), USN, Res Lab, Opt Sci Div, Code 5611,4555 Overlook Ave,SW, Washington, DC 20375 USA. EM justus@nrl.navy.mil NR 15 TC 47 Z9 47 U1 1 U2 7 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1559-128X EI 2155-3165 J9 APPL OPTICS JI Appl. Optics PD MAR 10 PY 2004 VL 43 IS 8 BP 1663 EP 1668 DI 10.1364/AO.43.001663 PG 6 WC Optics SC Optics GA 800YZ UT WOS:000220064900009 PM 15046169 ER PT J AU Insinga, A Monestiroli, S Ronzoni, S Carbone, R Pearson, M Pruneri, G Viale, G Appella, E Pelicci, P Minucci, S AF Insinga, A Monestiroli, S Ronzoni, S Carbone, R Pearson, M Pruneri, G Viale, G Appella, E Pelicci, P Minucci, S TI Impairment of p53 acetylation, stability and function by an oncogenic transcription factor SO EMBO JOURNAL LA English DT Article DE histone deacetylase; p53; PML; PML-RAR; promyelocytic leukemia ID ACUTE PROMYELOCYTIC LEUKEMIA; ACUTE MYELOID-LEUKEMIA; CHROMOSOMAL-ABNORMALITIES; TRANSGENIC MICE; HEMATOPOIETIC PROGENITORS; P53-DEPENDENT APOPTOSIS; HISTONE DEACETYLASES; PREMATURE SENESCENCE; TUMOR-SUPPRESSOR; STEM-CELLS AB Mutations of p53 are remarkably rare in acute promyelocytic leukemias (APLs). Here, we demonstrate that the APL-associated fusion proteins PML-RAR and PLZF-RAR directly inhibit p53, allowing leukemic blasts to evade p53-dependent cancer surveillance pathways. PML-RAR causes deacetylation and degradation of p53, resulting in repression of p53 transcriptional activity, and protection from p53-dependent responses to genotoxic stress. These phenomena are dependent on the expression of wild-type PML, acting as a bridge between p53 and PML-RAR. Recruitment of histone deacetylase (HDAC) to p53 and inhibition of p53 activity were abrogated by conditions that either inactivate HDACs or trigger HDAC release from the fusion protein, implicating recruitment of HDAC by PML-RAR as the mechanism underlying p53 inhibition. C1 European Inst Oncol, Dept Expt Oncol, I-20141 Milan, Italy. European Inst Oncol, Dept Pathol, I-20141 Milan, Italy. NCI, Cell Biol Lab, Bethesda, MD 20892 USA. IFOM FIRC Inst, Milan, Italy. Univ Milan, Dept Biomol Sci & Biotechnol, Milan, Italy. RP Pelicci, P (reprint author), European Inst Oncol, Dept Expt Oncol, Via Ripamonti 435, I-20141 Milan, Italy. EM pgpelicci@ieo.it; sminucci@ieo.it RI Minucci, Saverio/J-9669-2012 NR 57 TC 82 Z9 87 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0261-4189 J9 EMBO J JI Embo J. PD MAR 10 PY 2004 VL 23 IS 5 BP 1144 EP 1154 DI 10.1038/sj.emboj.7600109 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 810HA UT WOS:000220694200015 PM 14976551 ER PT J AU Nielsen, KH Szamecz, B Valasek, L Jivotovskaya, A Shin, BS Hinnebusch, AG AF Nielsen, KH Szamecz, B Valasek, L Jivotovskaya, A Shin, BS Hinnebusch, AG TI Functions of eIF3 downstream of 48S assembly impact AUG recognition and GCN4 translational control SO EMBO JOURNAL LA English DT Article DE eIF3; GCN4 translational control; multifactor complex (MFC); PRT1; yeast ID TEMPERATURE-SENSITIVE MUTANTS; SACCHAROMYCES-CEREVISIAE; IN-VIVO; MULTIFACTOR COMPLEX; INITIATION-FACTORS; MEDIATE BINDING; MESSENGER-RNA; YEAST; SUBUNITS; GTPASE AB The binding of eIF2-GTP-tRNA(i)(Met) ternary complex (TC) to 40S subunits is impaired in yeast prt1-1 (eIF3b) mutant extracts, but evidence is lacking that TC recruitment is a critical function of eIF3 in vivo. If TC binding was rate-limiting in prt1-1 cells, overexpressing TC should suppress the temperature-sensitive phenotype and GCN4 translation should be strongly derepressed in this mutant, but neither was observed. Rather, GCN4 translation is noninducible in prt1-1 cells, and genetic analysis indicates defective ribosomal scanning between the upstream open reading frames that mediate translational control. prt1-1 cells also show reduced utilization of a near-cognate start codon, implicating eIF3 in AUG selection. Using in vivo cross-linking, we observed accumulation of TC and mRNA/eIF4G on 40S subunits and a 48S 'halfmer' in prt1-1 cells. Genetic evidence suggests that 40S-60S subunit joining is not rate-limiting in the prt1-1 mutant. Thus, eIF3b functions between 48S assembly and subunit joining to influence AUG recognition and reinitiation on GCN4 mRNA. Other mutations that disrupt eIF2-eIF3 contacts in the multifactor complex (MFC) diminished 40S-bound TC, indicating that MFC formation enhances 43S assembly in vivo. C1 NICHHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. RP Hinnebusch, AG (reprint author), NICHHD, Lab Gene Regulat & Dev, NIH, Bldg 6A Room B1A-13, Bethesda, MD 20892 USA. EM ahinnebusch@nih.gov RI Valasek, Leos/I-5743-2014 NR 35 TC 73 Z9 74 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0261-4189 J9 EMBO J JI Embo J. PD MAR 10 PY 2004 VL 23 IS 5 BP 1166 EP 1177 DI 10.1038/sj.emboj.7600116 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 810HA UT WOS:000220694200017 PM 14976554 ER PT J AU Zhang, R Burke, LJ Rasko, JEJ Lobanenkov, V Renkawitz, R AF Zhang, R Burke, LJ Rasko, JEJ Lobanenkov, V Renkawitz, R TI Dynamic association of the mammalian insulator protein CTCF with centrosomes and the midbody SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE CTCF; cell cycle; centrosome; midbody; 2D gel ID THYROID-HORMONE RECEPTOR; POLO-LIKE KINASE; C-MYC GENE; CELL-CYCLE; ENHANCER BLOCKING; MITOTIC SPINDLE; EXPRESSION; PROMOTER; CYTOKINESIS; INHIBITION AB CTCF is a highly conserved, ubiquitously expressed DNA-binding protein that has widespread capabilities in gene regulation. CTCF plays important roles in cell growth regulatory processes and epigenetic functions. Ectopic expression of CTCF results in severe cell growth inhibition at multiple points within the cell cycle, indicating that CTCF levels must be stringently monitored. We have investigated the subcellular localization of CTCF in detail. Interestingly, we observe that CTCF shows a dynamic cell cycle-dependent distribution. Immunofluorescent staining reveals that in interphase CTCF is a nuclear protein, which is mainly excluded from the nucleolus. Strikingly, CTCF is associated with the centrosome during mitosis, especially from metaphase to anaphase. At telophase, CTCF dissociates from the centrosome and localizes to the midbody and the reformed nuclei. The association of CTCF with centrosomes and the midbody is further confirmed by biochemical fractionation. Moreover, subcellular fractions of CTCF show cell cycle and organelle-specific posttranslational modifications, suggesting different roles for CTCF at different stages of the cell cycle. (C) 2003 Elsevier Inc. All rights reserved. C1 Univ Giessen, Inst Genet, D-35392 Giessen, Germany. Univ Sydney, Royal Prince Alfred Hosp, Centenary Inst Canc Med & Cell Biol, Newtown, NSW 2042, Australia. Sydney Canc Ctr, Newtown, NSW 2042, Australia. NIAID, Immunopathol Lab, NIH, Bethesda, MD 20892 USA. RP Renkawitz, R (reprint author), Univ Giessen, Inst Genet, Heinrich Buff Ring 58-62, D-35392 Giessen, Germany. EM Rainer.Reinkawitz@gen.bio.uni-giessen.de RI Rasko, John/F-5754-2013; OI Lobanenkov, Victor/0000-0001-6665-3635 NR 31 TC 28 Z9 29 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD MAR 10 PY 2004 VL 294 IS 1 BP 86 EP 93 DI 10.1016/j.yexer.2003.11.015 PG 8 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 800KX UT WOS:000220028300010 PM 14980504 ER PT J AU Li, R Faria, TN Boehm, M Nabel, EG Gudas, LJ AF Li, R Faria, TN Boehm, M Nabel, EG Gudas, LJ TI Retinoic acid causes cell growth arrest and an increase in p27 in F9 wild type but not in F9 retinoic acid receptor beta(2) knockout cells SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE retinoic acid; retinoic acid receptors; RAR beta(2) knockout; cell cycle; p27; cyclins; Skp2; F9 cells; p21; cell cycle arrest ID EMBRYONAL CARCINOMA-CELLS; BREAST-CANCER CELLS; BRONCHIAL EPITHELIAL-CELLS; RXR-SELECTIVE RETINOIDS; KINASE INHIBITOR P27; LUNG-CANCER; UP-REGULATION; ESOPHAGEAL CANCER; MESSENGER-RNA; NEURONAL DIFFERENTIATION AB We have previously shown that an F9 teratocarcinoma retinoic acid receptor beta(2) (RARbeta(2)) knockout cell line exhibits no growth arrest in response to all-trans-retinoic acid (RA), whereas F9 wild type (Wt), F9 RARalpha(-/-), and F9 RARgamma(-/-) cell lines do growth arrest in response to RA. To examine the role of RARbeta(2) in growth inhibition, we analyzed the cell cycle regulatory proteins affected by RA in F9 Wt and F9 RARbeta(2)(-/-) cells. Flow micro fluorimetry analyses revealed that RA treatment of F9 Wt cells greatly increased the percentage of cells in the G1/G0 phase of the cell cycle. In contrast, RA did not alter the cell cycle distribution profile of RARbeta(2)(-/-) cells. In F9 Wt cells, cyclin D1, D3, and cyclin E protein levels decreased, while cyclin D2 and p27 levels increased after RA treatment. Compared to the F9 Wt cells, the F9 RARbeta(2)(-/-) cells exhibited lower levels of cyclins D I, D2, D3, and E in the absence of RA, but did not exhibit further changes in the levels of these cell cycle regulators after RA addition. Since RA significantly increased the level of p27 protein (approximately 24-fold) in F9 Wt as compared to the F9 RARbeta(2)(-/-) cells, we chose to study p27 in greater detail. The p27 mRNA level and the rate of p27 protein synthesis were increased in RA-treated F9 Wt cells, but not in F9 PARbeta(2)(-/-) cells. Moreover, RA increased the half-life of p27 protein in F9 Wt cells. Reduced expression of RARbeta(2) is associated with the process of carcinogenesis and RARbeta(2) can mediate the growth arrest induced by RA in a variety of cancer cells. Using both genetic and molecular approaches, we have identified some of the molecular mechanisms, such as the large elevation of p27, through which RARbeta(2) mediates these growth inhibitory effects of RA in F9 cells. (C) 2003 Elsevier Inc. All rights reserved. C1 Cornell Univ, Weill Coll Med, Dept Pharmacol, New York, NY 10021 USA. NHLBI, Cardiovasc Branch, NIH, Bethesda, MD 20892 USA. RP Gudas, LJ (reprint author), Cornell Univ, Weill Coll Med, Dept Pharmacol, E409,1300 York Ave, New York, NY 10021 USA. EM ljgudas@med.cornell.edu FU NCI NIH HHS [R01-CA43796] NR 92 TC 24 Z9 27 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD MAR 10 PY 2004 VL 294 IS 1 BP 290 EP 300 DI 10.1016/j.yexcr.2003.11.014 PG 11 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 800KX UT WOS:000220028300028 PM 14980522 ER PT J AU Lubin, JH Wang, ZY Boice, JD Xu, ZY Blot, WJ Wang, LD Kleinerman, RA AF Lubin, JH Wang, ZY Boice, JD Xu, ZY Blot, WJ Wang, LD Kleinerman, RA TI Risk of lung cancer and residential radon in China: Pooled results of two studies SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE radiation epidemiology; case-control studies; lung cancer; radon ID INDOOR RADON; EXPOSURE ASSESSMENT; MEASUREMENT ERROR; SMOKING; SWEDEN; MODELS AB Studies of radon-exposed underground miners predict that residential radon is the second leading cause of lung cancer mortality; however, case-control studies of residential radon have not provided unambiguous evidence of an association. Owing to small expected risks from residential radon and uncertainties in dosimetry, large studies or pooling of multiple studies are needed to fully evaluate effects. We pooled data from 2 case-control studies of residential radon representing 2 large radon studies conducted in China. The studies included 1,050 lung cancer cases and 1,996 controls. In the pooled data, odds ratios (OR) increased significantly with greater radon concentration. Based on a linear model, the OR with 95% confidence intervals (CI) at 100 Becquerel/cubic-meter (Bq/m(3)) was 1.33 (1.01,1.36). For subjects resident in the current home for 30 years or more, the OR at 100 Bq/m(3) was 1.32 (1.07,1.91). Results across studies were consistent with homogeneity. Estimates of ORs were similar to extrapolations from miner data and consistent with published residential radon studies in North American and Europe, suggesting long-term radon exposure at concentrations found in many homes increases lung cancer risk. (C) 2003 Wiley-Liss, Inc. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Liaoning Ctr Dis Control & Prevent, Shenyang, Peoples R China. Int Epidemiol Inst, Shenyang, Peoples R China. Minist Hlth, Beijing, Peoples R China. Minist Hlth, Lab Ind Hyg, Beijing, Peoples R China. RP Lubin, JH (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,MSC-7244, Bethesda, MD 20892 USA. EM lubinj@mail.nih.gov OI Kleinerman, Ruth/0000-0001-7415-2478 NR 35 TC 114 Z9 123 U1 3 U2 15 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 MAR 10 PY 2004 VL 109 IS 1 BP 132 EP 137 DI 10.1002/ijc.11683 PG 6 WC Oncology SC Oncology GA 770NF UT WOS:000188736300019 PM 14735479 ER PT J AU Dagdug, L Weiss, GH AF Dagdug, L Weiss, GH TI Suggested parameter to estimate the region probed by photons in laser-based measurements SO JOURNAL OF MODERN OPTICS LA English DT Article ID TIME-RESOLVED TRANSILLUMINATION; TURBID MEDIUM; PENETRATION; TISSUE; STATISTICS; MEDICINE; DEPTH AB In many biomedical applications of laser radiation to estimate optical parameters in tissue, it is desirable, if not crucial, to describe the region being probed. We suggest a parameter for this purpose, based on a lattice random walk on a simple cubic lattice. It is the expected number of distinct sites visited by a random walker. This is relatively easy to compute, although higher moments are not. Detailed computations are given for a continuous-wave measurement on a semi-infinite medium bounded by an absorbing plane and for a slab geometry required to analyse transillumination experiments. C1 NIH, Math & Stat Comp Lab, Ctr Informat Technol, Bethesda, MD 20892 USA. RP Dagdug, L (reprint author), NIH, Math & Stat Comp Lab, Ctr Informat Technol, Bldg 10, Bethesda, MD 20892 USA. NR 19 TC 1 Z9 1 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0950-0340 EI 1362-3044 J9 J MOD OPTIC JI J. Mod. Opt. PD MAR 10 PY 2004 VL 51 IS 4 BP 469 EP 478 DI 10.1080/0950034031000121740 PG 10 WC Optics SC Optics GA 762QP UT WOS:000187993900001 ER PT J AU Genoud, C Knott, GW Sakata, K Lu, B Welker, E AF Genoud, C Knott, GW Sakata, K Lu, B Welker, E TI Altered synapse formation in the adult somatosensory cortex of brain-derived neurotrophic factor heterozygote mice SO JOURNAL OF NEUROSCIENCE LA English DT Article DE BDNF; barrel; plasticity; synapse; GABA; spine; ultrastructure ID LONG-TERM POTENTIATION; RAT VISUAL-CORTEX; MONOCULAR DEPRIVATION DECREASES; DOMINANCE COLUMN FORMATION; MESSENGER-RNA EXPRESSION; BDNF KNOCKOUT MICE; BARREL CORTEX; DENDRITIC SPINES; HIPPOCAMPAL-NEURONS; CRITICAL PERIOD AB Increased sensory stimulation in the adult whisker-to-barrel pathway induces the expression of BDNF as well as synapse formation in cortical layer IV. Here, we investigated whether BDNF plays a role in the alterations of connectivity between neurons by analyzing the ultrastructure of the BDNF heterozygote mouse, characterized by a reduced level of BDNF expression. Using serial section electron microscopy, we measured synapse density, spine morphology, and synaptic vesicle distribution to show that mice with a reduced level of BDNF have a barrel neuropil that is indistinguishable from wild-type controls. After 24 hr of whisker stimulation, however, there is no indication of synapse formation in the heterozygous mouse. Whereas the balance between excitatory and inhibitory synapses is modified in the controls, it remains constant in the heterozygotes. The distribution of synaptic vesicles in excitatory synapses is the same in heterozygous and wild-type mice and is not influenced by the stimulation paradigm. Spine volume, however, is unchanged by stimulation in the wild-type animals, but does increase significantly in the heterozygous animal. These results provide evidence that, in vivo, BDNF plays an important role in the structural rearrangement of adult cortical circuitry as a consequence of an increased sensory input. C1 Inst Biol Cellulaire & Morphol, CH-1005 Lausanne, Switzerland. NICHHD, Sect Neural Dev & Plast, Bethesda, MD 20892 USA. RP Welker, E (reprint author), Inst Biol Cellulaire & Morphol, Rue Bugnon 9, CH-1005 Lausanne, Switzerland. EM Egbert.Welker@IBCM.unil.ch RI Lu, Bai/A-4018-2012 NR 38 TC 70 Z9 70 U1 0 U2 3 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAR 10 PY 2004 VL 24 IS 10 BP 2394 EP 2400 DI 10.1523/JNEUROSCI.4040-03.2004 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 801XY UT WOS:000220129800006 PM 15014114 ER PT J AU Tessarollo, L Coppola, V Fritzsch, B AF Tessarollo, L Coppola, V Fritzsch, B TI NT-3 replacement with brain-derived neurotrophic factor redirects vestibular nerve fibers to the cochlea SO JOURNAL OF NEUROSCIENCE LA English DT Article DE cochlea; ear; guidance; neurotrophic; neurotropic; vestibular ID NULL MUTANT MICE; INNER-EAR; SYSTEM DEVELOPMENT; SENSORY NEURONS; MESSENGER-RNAS; IN-VIVO; BDNF; INNERVATION; EXPRESSION; RECEPTORS AB Survival of inner ear sensory neurons depends on two neurotrophins, BDNF and NT-3, and their respective receptors, TrkB and TrkC. Because both receptors are present in the same neuron, it has been suggested that BDNF and NT-3 are functionally redundant in promoting neuronal survival. Knock- in of one ligand into the locus of the other one confirmed this hypothesis for the cochlea, leaving open the question of why two neurotrophins are required for proper innervation of the mammalian ear. Here, we show that the precise spatiotemporal pattern of expression of the two neurotrophins is essential for proper patterning of the inner ear innervation. Mice expressing BDNF under the control of the NT-3 promoter develop exuberant projections of vestibular sensory neurons to the basal turn of the cochlea. This projection can be enhanced by combining the transgene with a null mutation of BDNF. However, vestibular fibers rerouted into the cochlea do not reach hair cells and remain outside the organ of Corti, suggesting a chemotactic role for neurotrophins on these fibers. Our data provide genetic evidence that neurotrophins in the ear exert both survival and axon guidance roles. C1 Creighton Univ, Dept Biomed Sci, Omaha, NE 68178 USA. NCI, Neural Dev Grp, Mouse Canc Genet Program, Frederick, MD 21701 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 DC005590-03, R01 DC005590] NR 44 TC 69 Z9 70 U1 0 U2 2 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAR 10 PY 2004 VL 24 IS 10 BP 2575 EP 2584 DI 10.1523/JNEUROSCI.5514-03.2004 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 801XY UT WOS:000220129800025 PM 15014133 ER PT J AU Clore, GM Schwieters, CD AF Clore, GM Schwieters, CD TI How much backbone motion in ubiquitin is required to account for dipolar coupling data measured in multiple alignment media as assessed by independent cross-validation? SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID MOLECULAR-DYNAMICS SIMULATIONS; NUCLEAR MAGNETIC-RESONANCE; PROTEIN-PROTEIN COMPLEXES; LIQUID-CRYSTALLINE PHASE; MODEL-FREE APPROACH; NMR STRUCTURES; DISTANCE RESTRAINTS; ORIENTED MEDIA; STATE NMR; MACROMOLECULES AB The magnitude of backbone internal motions in the small protein ubiquitin that needs to be invoked to account for dipolar coupling data measured in multiple alignment media is investigated using an intuitively straightforward approach. This involves simultaneous refinement of the coordinates (against NOE, torsion angle, and dipolar coupling restraints) and optimization of the magnitudes and orientations of the alignment tensors; by means of torsion angle simulated annealing and Cartesian space minimization. We show that N-H dipolar couplings in 11 different alignment media and N-C', H-N-C', and Calpha-C' dipolar coupling in two alignment media can be accounted for, at approximately the level of uncertainty in the experimental data, by a single structure representation. Extension to a two-member ensemble representation which provides the simplest description of anisotropic motions in the form of a two-site jump model (in which the overall calculated dipolar couplings are the averages of the calculated dipolar couplings of the individual ensemble members), results in modest, but significant, improvements in dipolar coupling R-factors for both the working set of couplings used in the refinement and for the free cross-validated set of Calpha-Halpha dipolar couplings recorded in two alignment media. Extensions to larger ensemble sizes do not result in any R-factor improvement for the cross-validated C(x-H(x dipolar couplings. With a few notable exceptions, the amplitudes of the anisotropic motions are small, with S-2(jump) order parameters greater than or equal to0.8. Moreover, the structural impact of those few residues that do exhibit larger amplitude motions (S2(jump) ranging from 0.3 to 0.8) is minimal and can readily be accommodated by very small backbone atomic rms shifts (<0.5 Angstrom) because of compensatory changes in phi and psi backbone torsion angles. In addition, evidence for correlated motions of N-H bond vectors is observed. For most practical applications, however, refinement of NMR structures against dipolar couplings using a single structure representation is adequate and will not adversely impact coordinate accuracy within the limits of the NMR method. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. NIH, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA. RP Clore, GM (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 5, Bethesda, MD 20892 USA. EM mariusc@intra.niddk.nih.gov; charles.schwieters@nih.gov RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 54 TC 147 Z9 149 U1 1 U2 10 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD MAR 10 PY 2004 VL 126 IS 9 BP 2923 EP 2938 DI 10.1021/ja0386804 PG 16 WC Chemistry, Multidisciplinary SC Chemistry GA 800OY UT WOS:000220038800056 PM 14995210 ER PT J AU Novoradovskaya, N Whitfield, ML Basehore, LS Novoradovsky, A Pesich, R Usary, J Karaca, M Wong, WK Aprelikova, O Fero, M Perou, CM Botstein, D Braman, J AF Novoradovskaya, N Whitfield, ML Basehore, LS Novoradovsky, A Pesich, R Usary, J Karaca, M Wong, WK Aprelikova, O Fero, M Perou, CM Botstein, D Braman, J TI Universal Reference RNA as a standard for microarray experiments SO BMC GENOMICS LA English DT Article ID GENE-EXPRESSION PATTERNS; DNA MICROARRAYS; EXPERIMENTAL-DESIGN; DIVERSITY; TUMORS AB Background: Obtaining reliable and reproducible two-color microarray gene expression data is critically important for understanding the biological significance of perturbations made on a cellular system. Microarray design, RNA preparation and labeling, hybridization conditions and data acquisition and analysis are variables difficult to simultaneously control. A useful tool for monitoring and controlling intra- and inter-experimental variation is Universal Reference RNA (URR), developed with the goal of providing hybridization signal at each microarray probe location ( spot). Measuring signal at each spot as the ratio of experimental RNA to reference RNA targets, rather than relying on absolute signal intensity, decreases variability by normalizing signal output in any two-color hybridization experiment. Results: Human, mouse and rat URR (UHRR, UMRR and URRR, respectively) were prepared from pools of RNA derived from individual cell lines representing different tissues. A variety of microarrays were used to determine percentage of spots hybridizing with URR and producing signal above a user defined threshold (microarray coverage). Microarray coverage was consistently greater than 80% for all arrays tested. We confirmed that individual cell lines contribute their own unique set of genes to URR, arguing for a pool of RNA from several cell lines as a better configuration for URR as opposed to a single cell line source for URR. Microarray coverage comparing two separately prepared batches each of UHRR, UMRR and URRR were highly correlated (Pearson's correlation coefficients of 0.97). Conclusion: Results of this study demonstrate that large quantities of pooled RNA from individual cell lines are reproducibly prepared and possess diverse gene representation. This type of reference provides a standard for reducing variation in microarray experiments and allows more reliable comparison of gene expression data within and between experiments and laboratories. C1 Stratagene, La Jolla, CA 92037 USA. Stanford Univ, Howard Hughes Med Inst, Dept Genet, Stanford, CA 94305 USA. Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Pathol & Lab Med, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. NCI, NIH, Bethesda, MD 20892 USA. Dartmouth Coll, Sch Med, Dept Genet, Hanover, NH 03755 USA. Princeton Univ, Lewis Sigler Inst Integrat Genom, Carl Icahn Lab 140, Princeton, NJ 08544 USA. RP Novoradovskaya, N (reprint author), Stratagene, 11011 N Torrey Pines Rd, La Jolla, CA 92037 USA. EM nnovo@stratagene.com; Michael.Whitfield@Dartmouth.edu; Scott.Basehore@stratagene.com; anovo@stratagene.com; rspesich@genome.stanford.edu; usary@unc.edu; mehmet_karaca@med.unc.edu; Winston.Wong@stratagene.com; apreliko@mail.nih.gov; mfero@genome.stanford.edu; cperou@med.unc.edu; botstein@princeton.edu; Jeff.Braman@stratagene.com RI Karaca, Mehmet/C-2683-2009 OI Karaca, Mehmet/0000-0003-3219-9109 FU NHGRI NIH HHS [F32 HG000220-02, F32 HG000220, F32 HG000220-01, F32 HG000220-03] NR 23 TC 101 Z9 103 U1 0 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PD MAR 9 PY 2004 VL 5 AR 20 DI 10.1186/1471-2164-5-20 PG 13 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 820HQ UT WOS:000221378900001 PM 15113400 ER PT J AU Janket, SJ Qvarnstrom, M Meurman, JH Baird, AE Nuutinen, P Jones, JA AF Janket, SJ Qvarnstrom, M Meurman, JH Baird, AE Nuutinen, P Jones, JA TI Asymptotic dental score and prevalent coronary heart disease SO CIRCULATION LA English DT Article DE oral health; heart diseases; lipoproteins; interleukins; fibrinogen ID C-REACTIVE PROTEIN; CARDIOVASCULAR RISK-FACTORS; PERIODONTAL-DISEASE; MYOCARDIAL-INFARCTION; ORAL-HEALTH; TOOTH LOSS; PREDICTION; STROKE; WOMEN; ATHEROSCLEROSIS AB Background - Oral infections have been postulated to produce cytokines that may contribute to the pathogenesis of coronary heart disease (CHD). We hypothesized that by estimating the combined production of inflammatory mediators attributable to several oral pathologies, we might be able to explain CHD with better precision. Methods and Results - A total of 256 consecutive Finnish cardiac patients from Kuopio University Hospital with angiographically confirmed CHD and 250 age-, gender-, and residence-matched noncardiac patients ( controls) were recruited. All dental factors expected to generate inflammatory mediators, including pericoronitis, dental caries, dentate status, root remnants, and gingivitis, were examined, and an asymptotic dental score ( ADS) was developed by logistic regression analyses with an appropriate weighting scheme according to the likelihood ratio. We validated the explanatory ability of ADS by comparing it to that of the Total Dental Index and examining whether the ADS was associated with known predictors of CHD. A model that included ADS, C-reactive protein, HDL, and fibrinogen offered an explanatory ability that equaled or exceeded that of the Framingham heart score ( C statistic = 0.82 versus 0.80). When ADS was removed from this model, the C-statistic decreased to 0.77, which indicates that the ADS was a significant contributor to the explanatory ability of a logistic model. Conclusions - ADS may be useful as a prescreening tool to promote proactive cardiac evaluation among individuals without overt symptoms of CHD. However, additional prospective study is needed to validate the use of an oral health score as a predictor of incident CHD. C1 Boston Univ, Goldman Sch Grad Dent Med, Dept Gen Dent, Boston, MA 02118 USA. Kuopio Univ Hosp, Dept Otorhinolaryngol Oral Surg, SF-70210 Kuopio, Finland. Kuopio Univ Hosp, Dept Cardiothorac Surg, SF-70210 Kuopio, Finland. Univ Helsinki, Cent Hosp, Dept Oral & Maxillofacial Dis, Helsinki, Finland. NINDS, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. VA Ctr Hlth Qual Outcomes & Econ Res, Bedford, MA USA. RP Janket, SJ (reprint author), Boston Univ, Goldman Sch Grad Dent Med, Dept Gen Dent, 100 E Newton St, Boston, MA 02118 USA. EM sjanket@hsph.harvard.edu OI Janket, Sok-Ja/0000-0003-0078-3992; Jones, Judith/0000-0002-0126-0790; Meurman, Jukka/0000-0001-6702-6836 NR 30 TC 50 Z9 50 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 9 PY 2004 VL 109 IS 9 BP 1095 EP 1100 DI 10.1161/01.CIR.0000118497.44961.1E PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 801FZ UT WOS:000220083100008 PM 14967717 ER PT J AU Sandstrom, DJ Nash, H AF Sandstrom, DJ Nash, H TI Drug targets: Turning the channel (on) for sedation SO CURRENT BIOLOGY LA English DT Editorial Material ID POTASSIUM CHANNELS; C-ELEGANS; RECEPTOR; SUBUNIT; ETHANOL; RESPONSES; ALCOHOL AB Genetic techniques have recently implicated two different ion channels as critical molecular targets for the sedative action of ethanol and intravenous anesthetics. In each case, the target is hyperactivated by the drug. C1 NIMH, NIH, Bethesda, MD 20892 USA. RP Sandstrom, DJ (reprint author), NIMH, NIH, Bldg 36,Rm 1B08,MSC 4034, Bethesda, MD 20892 USA. NR 15 TC 2 Z9 2 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD MAR 9 PY 2004 VL 14 IS 5 BP R185 EP R186 DI 10.1016/j.cub.2004.02.016 PG 2 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 803HQ UT WOS:000220222600011 PM 15028232 ER PT J AU Frank, JA Richert, N Bash, C Stone, L Calabresi, PA Lewis, B Stone, R Howard, T Mcfarland, HF AF Frank, JA Richert, N Bash, C Stone, L Calabresi, PA Lewis, B Stone, R Howard, T Mcfarland, HF TI Interferon-beta-1b slows progression of atrophy in RRMS - Three-year follow-up in NAb- and NAb+ patients SO NEUROLOGY LA English DT Article ID REMITTING MULTIPLE-SCLEROSIS; PLACEBO-CONTROLLED TRIAL; WHOLE-BRAIN ATROPHY; NEUTRALIZING ANTIBODIES; CEREBRAL ATROPHY; QUANTITATIVE-ANALYSIS; ENHANCING LESIONS; WHITE-MATTER; DOUBLE-BLIND; AXONAL LOSS AB Objective: To determine the effect of interferon-beta-1b (IFNbeta-1b) treatment on total contrast-enhancing lesions (CEL), white matter lesion load (WMLL), and cerebral atrophy ( CA) in patients with relapsing - remitting multiple sclerosis (RRMS) using serial monthly MRI. Methods: An open-label baseline-vs-treatment crossover trial was conducted with 30 RRMS patients monitored during a 6-month baseline and up to 36 months on treatment with IFNbeta-1b. Monthly MRI exams and neurologic exams using the Expanded Disability Status Scale (EDSS) were performed. Results: The percentage changes from baseline for years 1, 2, and 3 on IFNbeta-1b were as follows: brain volume (BV) = - 1.35, - 1.48, and - 1.68%; CEL = - 76.5, - 60.1, and - 54.7%; WMLL = - 12.2, - 9.8, and - 10.4%. There was no difference in the BV, CEL, or WMLL for between-year comparisons, and the decrease in BV from year 1 to years 2 and 3 was less than the change from baseline to year 1. EDSS did increase ( p < 0.001) when comparing the last 3 months of baseline (2.8 +/- 2.1) and the last 3 months on IFNβ-1b (3.6 +/- 2.1). Eleven patients developed neutralizing antibody (NAb) during the study. The effect of IFNβ-1b on CEL and WMLL was significantly reduced in NAb+ patients compared with NAb- patients ( p < 0.003). Conclusion: IFNbeta-1b decreases contrast-enhancing lesions and white matter lesion load over 3 years on therapy and slows the progression in cerebral atrophy during years 2 and 3. C1 NINDS, Expt Neuroimaging Sect, Lab Diagnost Radiol Res, NIH, Bethesda, MD 20892 USA. NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. Johns Hopkins Univ, Baltimore, MD USA. Cleveland Clin, Cleveland, OH 44106 USA. RP Frank, JA (reprint author), NINDS, Expt Neuroimaging Sect, Lab Diagnost Radiol Res, NIH, 10 Ctr Dr,MSC 1074,Bldg 10,Rm B1N256, Bethesda, MD 20892 USA. EM jafrank@helix.nih.gov NR 35 TC 59 Z9 59 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAR 9 PY 2004 VL 62 IS 5 BP 719 EP 725 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 801FY UT WOS:000220083000009 PM 15007120 ER PT J AU Bogdanov, EI Heiss, JD Mendelevich, EG Mikhaylov, IM Haass, A AF Bogdanov, EI Heiss, JD Mendelevich, EG Mikhaylov, IM Haass, A TI Clinical and neuroimaging features of "idiopathic" syringomyelia SO NEUROLOGY LA English DT Article ID MALFORMATION; HERNIATION; SYRINX; MR AB In some adult patients with cervical syringomyelia, MRI studies do not identify primary disease within the foramen magnum or spinal canal. To identify the etiology of this idiopathic type of syringomyelia, clinical features and posterior fossa (PF) measurements from 17 of these patients, 17 patients with Chiari I-type syringomyelia, and 32 control subjects were compared. Idiopathic syringomyelia and Chiari I-type syringomyelia manifested central cervical myelopathy and a small PF with narrow CSF spaces, suggesting that they develop by the same mechanism. C1 Kazan State Med Univ, Dept Neurol & Rehabil, Kazan, Russia. Interreg Clin Diagnost Ctr, Kazan, Russia. NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. Univ Saarland, Dept Neurol, D-6650 Homburg, Germany. RP Bogdanov, EI (reprint author), Kazan State Med Univ, Dept Neurol & Rehabil, Butlerov Str 49, Kazan, Russia. EM enver_bogdanov@mail.ru OI Bogdanov, E.I./0000-0001-9332-8053 FU Intramural NIH HHS [ZIA NS003050-05] NR 10 TC 27 Z9 31 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAR 9 PY 2004 VL 62 IS 5 BP 791 EP 794 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 801FY UT WOS:000220083000023 PM 15007134 ER PT J AU Ng, L Goodyear, RJ Woods, CA Schneider, MJ Diamond, E Richardson, GP Kelley, MW St Germain, DL Galton, VA Forrest, D AF Ng, L Goodyear, RJ Woods, CA Schneider, MJ Diamond, E Richardson, GP Kelley, MW St Germain, DL Galton, VA Forrest, D TI Hearing loss and retarded cochlear development in mice lacking type 2 iodothyronine deiodinase SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE deafness; thyroid hormone receptor ID THYROID-HORMONE RECEPTORS; GENE-EXPRESSION; TECTORIAL MEMBRANE; AUDITORY FUNCTION; NEONATAL RATS; RESISTANCE; BETA; HYPOTHYROIDISM; MOUSE; ONSET AB The later stages of cochlear differentiation and the developmental onset of hearing require thyroid hormone. Although thyroid hormone receptors (TRs) are a prerequisite for this process, it is likely that other factors modify TR activity during cochlear development. The mouse cochlea expresses type 2 deiodinase (D2), an enzyme that converts thyroxine, the main form of thyroid hormone in the circulation, into 3,5,3'-triiodothyronine (T3) the major ligand for TRs. Here, we show that D2-deficient mice have circulating thyroid hormone levels that would normally be adequate to allow hearing to develop but they exhibit an auditory phenotype similar to that caused by systemic hypothyroidism or TR deletions. D2-deficient mice have defective auditory function, retarded differentiation of the cochlear inner sulcus and sensory epithelium, and deformity of the tectorial membrane. The similarity of this phenotype to that caused by TR deletions suggests that D2 controls the T3 signal that activates TRs in the cochlea. Thus, D2 is essential for hearing, and the results suggest that this hormone-activating enzyme confers on the cochlea the ability to stimulate its own T3 response at a critical developmental period. C1 CUNY Mt Sinai Sch Med, Dept Human Genet, New York, NY 10029 USA. CUNY Mt Sinai Sch Med, Dept Med, New York, NY 10029 USA. Dartmouth Coll Sch Med, Dept Physiol, Lebanon, NH 03756 USA. Dartmouth Coll Sch Med, Dept Med, Lebanon, NH 03756 USA. Natl Inst Deafness & Other Commun Disorders, Sec Dev Neurosci, NIH, Rockville, MD 20850 USA. Univ Sussex, Sch Biol Sci, Brighton BN1 9QG, E Sussex, England. CUNY Mt Sinai Sch Med, Dept Med, New York, NY 10029 USA. RP Forrest, D (reprint author), CUNY Mt Sinai Sch Med, Dept Human Genet, New York, NY 10029 USA. EM douglas.forrest@mssm.edu FU NICHD NIH HHS [HD-09020, R01 HD009020]; NIDCD NIH HHS [DC-03441, R01 DC003441]; NIDDK NIH HHS [R01 DK042271, DK-42271] NR 35 TC 121 Z9 122 U1 2 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 9 PY 2004 VL 101 IS 10 BP 3474 EP 3479 DI 10.1073/pnas.0307402101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 802LA UT WOS:000220163800028 PM 14993610 ER PT J AU Wexler, NS AF Wexler, NS CA US Venezuala Collaborative Res TI Venezuelan kindreds reveal that genetic and environmental factors modulate Huntington's disease age of onset SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID TRINUCLEOTIDE REPEAT; CAG REPEAT; ASSOCIATION; EXPANSION; FEATURES; LENGTH AB Huntington's disease (HID) is an autosomal dominant neurodegenerative disease caused by a triplet (CAG) expansion mutation. The length of the triplet repeat is the most important factor in determining age of onset of HID, although substantial variability remains after controlling for repeat length. The Venezuelan HID kindreds encompass 18,149 individuals spanning 10 generations, 15,409 of whom are living. Of the 4,384 immortalized lymphocyte lines collected, 3,989 DNAs were genotyped for their HD alleles, representing a subset of the population at greatest genetic risk. There are 938 heterozygotes, 80 people with variably penetrant alleles, and 18 homozygotes. Analysis of the 83 kindreds that comprise the Venezuelan HID kindreds demonstrates that residual variability in age of onset has both genetic and environmental components. We created a residual age of onset phenotype from a regression analysis of the log of age of onset on repeat length. Familial correlations (correlation SE) were estimated for sibling (0.40 +/- 0.09), parent-offspring (0.10 +/- 0.11), avuncular (0.07 +/- 0.11), and cousin (0.15 +/- 0.10) pairs, suggesting a familial origin for the residual variance in onset. By using a variance-components approach with all available familial relationships, the additive genetic heritability of this residual age of onset trait is 38%. A model, including shared sibling environmental effects, estimated the components of additive genetic (0.37), shared environment (0.22), and nonshared environment (0.41) variances, confirming that approximate to40% of the variance remaining in onset age is attributable to genes other than the HID gene and 60% is environmental. C1 Columbia Univ, New York, NY 10032 USA. Univ Ulm, D-89069 Ulm, Germany. Albany Med Coll, Albany, NY 12208 USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. CUNY, New York, NY 10016 USA. Univ Iowa, Iowa City, IA 52242 USA. Thomas Jefferson Univ, Philadelphia, PA 19107 USA. Univ Alabama, Birmingham, AL 35294 USA. Univ Calif Irvine, Irvine, CA 92697 USA. NINDS, NIH, Bethesda, MD 20892 USA. NYU, New York, NY 10016 USA. Hlth & Human Serv Agcy, San Diego, CA 92102 USA. Mt Sinai Med Ctr, Miami Beach, FL 33140 USA. Univ So Calif, Los Angeles, CA 90089 USA. N Shore Univ Hosp, Manhasset, NY 11030 USA. Miami Childrens Hosp, Miami, FL 33155 USA. Univ Rochester, Rochester, NY 14620 USA. Univ S Florida, Tampa, FL 33612 USA. Univ Texas, Houston, TX 77030 USA. Hosp Virgen del Camino, Pamplona 31008, Spain. Univ Calif Los Angeles, Mattel Childrens Hosp, Los Angeles, CA 90095 USA. Univ Zulia, Maracaibo 4011, Venezuela. MIT, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Charlestown, MA 02129 USA. Indiana Univ, Indianapolis, IN 46202 USA. Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England. RP Wexler, NS (reprint author), Columbia Univ, 1051 Riverside Dr, New York, NY 10032 USA. EM wexlern@pi.cpmc.columbia.edu RI Cherny, Stacey/B-3315-2008 OI Cherny, Stacey/0000-0002-0269-3352 NR 32 TC 326 Z9 334 U1 4 U2 24 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 9 PY 2004 VL 101 IS 10 BP 3498 EP 3503 DI 10.1073/pnas.0308479101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 802LA UT WOS:000220163800033 PM 14993615 ER PT J AU Smith, DL Dushoff, J Perencevich, EN Harris, AD Levin, SA AF Smith, DL Dushoff, J Perencevich, EN Harris, AD Levin, SA TI Persistent colonization and the spread of antibiotic resistance in nosocomial pathogens: Resistance is a regional problem SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID INTENSIVE-CARE UNITS; STAPHYLOCOCCUS-AUREUS INFECTIONS; ENTEROCOCCUS-FAECIUM; TRANSMISSION DYNAMICS; MATHEMATICAL-MODELS; HOSPITAL SETTINGS; RISK-FACTORS; METHICILLIN; CARRIAGE; EPIDEMIOLOGY AB Infections with anti biotic-resistant bacteria (ARB) in hospitalized patients are becoming increasingly frequent despite extensive infection-control efforts. Infections with ARB are most common in the intensive care units of tertiary-care hospitals, but the underlying cause of the increases may be a steady increase in the number of asymptomatic carriers entering hospitals. Carriers may shed ARB for years but remain undetected, transmitting ARB to others as they move among hospitals, long-term care facilities, and the community. We apply structured population models to explore the dynamics of ARB, addressing the following questions: (i) What is the relationship between the proportion of carriers admitted to a hospital, transmission, and the risk of infection with ARB? (ii) How do frequently hospitalized patients contribute to epidemics of ARB? (iii) How do transmission in the community, long-term care facilities, and hospitals interact to determine the proportion of the population that is carrying ARB? We offer an explanation for why ARB epidemics have fast and slow phases and why resistance may continue to increase despite infection-control efforts. To successfully manage ARB at tertiary-care hospitals, regional coordination of infection control may be necessary, including tracking asymptomatic carriers through health-care systems. C1 NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. Univ Maryland, Dept Epidemiol & Prevent Med, Sch Med, Baltimore, MD 21201 USA. Princeton Univ, Princeton, NJ 08544 USA. RP Smith, DL (reprint author), NIH, Fogarty Int Ctr, Room 309,Bldg 16,16 Ctr Dr, Bethesda, MD 20892 USA. EM smitdave@helix.nih.gov RI Smith, David/L-8850-2013 OI Smith, David/0000-0003-4367-3849 NR 60 TC 90 Z9 92 U1 2 U2 14 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 9 PY 2004 VL 101 IS 10 BP 3709 EP 3714 DI 10.1073/pnas.0400456101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 802LA UT WOS:000220163800069 PM 14985511 ER PT J AU Zhang, XC Marchand, C Pommier, Y Burke, TR AF Zhang, XC Marchand, C Pommier, Y Burke, TR TI Design and synthesis of photoactivatable aryl diketo acid-containing HIV-1 integrase inhibitors as potential affinity probes SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article ID STRAND TRANSFER; REPLICATION; CELLS AB Aryl diketo acids (ADKs) represent an important new class of HIV-1 integrase (IN) inhibitors. In order to facilitate examination of the structural basis underlying IN.ADK interaction, biphenyl ketone and phenyl azide photophores were incorporated into ADK structures. Of particular note is the novel dual utilization of azide and phenyketone moieties for both enzyme recognition and for crosslinking. The resulting analogues maintained low micromolar inhibitory potency against IN in recombinant in vitro assays. These potential HIV-1 integrase photoaffinity labels may provide useful tools for studying enzyme interactions of the ADK inhibitor class. Published by Elsevier Ltd. C1 NCI, Canc Res Ctr, Med Chem Lab, Frederick, MD 21702 USA. NCI, Lab Mol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Burke, TR (reprint author), NCI, Canc Res Ctr, Med Chem Lab, POB B,Bldg 376 Boyles St, Frederick, MD 21702 USA. EM tburke@helix.nih.gov RI Burke, Terrence/N-2601-2014; Marchand, Christophe/D-8559-2016 NR 13 TC 16 Z9 16 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD MAR 8 PY 2004 VL 14 IS 5 BP 1205 EP 1207 DI 10.1016/j.bmcl.2003.12.064 PG 3 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 779RR UT WOS:000189314800029 PM 14980666 ER PT J AU Yim, JJ Ding, L Schaffer, AA Park, GY Shim, YS Holland, SM AF Yim, JJ Ding, L Schaffer, AA Park, GY Shim, YS Holland, SM TI A microsatellite polymorphism in intron 2 of human Toll-like receptor 2 gene: functional implications and racial differences SO FEMS IMMUNOLOGY AND MEDICAL MICROBIOLOGY LA English DT Article DE toll-like receptor 2; micfosatellite polymorphism; interferon-gamma; GM-CSF ID SYSTEMIC LUPUS-ERYTHEMATOSUS; CELL WALL COMPONENTS; INTERFERON-GAMMA; INNATE IMMUNITY; REPEAT POLYMORPHISM; MATRIX-METALLOPROTEINASE-9 GENE; DINUCLEOTIDE REPEAT; JAPANESE PATIENTS; DROSOPHILA TOLL; CUTTING EDGE AB The human Toll-like receptor 2 (TLR2) mediates responses of both innate and adaptive immunity to Gram-positive bacteria, including mycobacteria. We sought functional polymorphisms in the 5'-untranslated region (UTR) of TLR2. We found a highly polymorphic (GT)n dinucleotide repeat 100 bp upstream of the TLR2 translational start site in intron 2. The numbers of GT repeats varied from 12 to 28. There were significant differences in allele distribution between African Americans and Caucasians (P = 0.008) and between African Americans and Koreans (P = 0.0003). The promoter activities of recombinant promoter-intron2/reporter constructs including the shortest [(GT)n = 12] or longest [(GT)n = 28] alleles were significantly more stimulated when exposed to 200 IU ml(-1) of interferon-gamma than when exposed to 100 IU ml(-1) of GM-CSF (P less than or equal to 0.03). Since TLR2 plays a critical role in the human innate immune response, this functional microsatellite polymorphism. may be important in the pathogenesis of infectious and inflammatory diseases. (C) 2003 Federation of European Microbiological Societies. Published by Elsevier B.V. All rights reserved. C1 NIAID, Immunopathogenesis Sect, Host Def Lab, Dept Hlth & Human Serv,NIH, Bethesda, MD 20892 USA. Natl Ctr Biotechnol Informat, Computat Biol Branch, Dept Hlth & Human Serv, NIH, Bethesda, MD USA. Gachon Med Sch, Gil Med Ctr, Dept Internal Med, Div Pulm, Inchon, South Korea. RP Holland, SM (reprint author), NIAID, Immunopathogenesis Sect, Host Def Lab, Dept Hlth & Human Serv,NIH, Bldg 10,Room 11N103,10 Ctr Dr,MSC 1886, Bethesda, MD 20892 USA. EM smh@nih.gov RI Schaffer, Alejandro/F-2902-2012; Yim, Jae Joon/J-2783-2012 NR 44 TC 48 Z9 50 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0928-8244 J9 FEMS IMMUNOL MED MIC JI FEMS Immunol. Med. Microbiol. PD MAR 8 PY 2004 VL 40 IS 2 BP 163 EP 169 DI 10.1016/S0928-8244(03)00342-0 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 801MO UT WOS:000220100200009 PM 14987735 ER PT J AU Hacke, W Donnan, G Fieschi, C Kaste, M von Kummer, R Broderick, JP Brott, T Frankel, M Grotta, JC Haley, EC Kwiatkowski, T Levine, SR Lewandowski, C Lu, M Lyden, P Marler, JR Patel, S Tilley, BC Albers, G Brott, T Grotta, J Bluhmki, PE Wilhelm, M Hamilton, S AF Hacke, W Donnan, G Fieschi, C Kaste, M von Kummer, R Broderick, JP Brott, T Frankel, M Grotta, JC Haley, EC Kwiatkowski, T Levine, SR Lewandowski, C Lu, M Lyden, P Marler, JR Patel, S Tilley, BC Albers, G Brott, T Grotta, J Bluhmki, PE Wilhelm, M Hamilton, S CA ATLANTIS Study Grp Investigators ECASS Study Grp Investigators NINDS Rt-PA Study Grp Investigato TI Association of outcome with early stroke treatment: pooled analysis of ATLANTIS, ECASS, and NINDS rt-PA stroke trials SO LANCET LA English DT Article ID ACUTE ISCHEMIC-STROKE; TISSUE-PLASMINOGEN ACTIVATOR; ACUTE MYOCARDIAL-INFARCTION; THROMBOLYTIC THERAPY; DOUBLE-BLIND; T-PA; ALTEPLASE; TIME AB Background Quick administration of intravenous recombinant tissue plasminogen activator (rt-PA) after stroke improved outcomes in previous trials. We aimed to analyse combined data for individual patients to confirm the importance of rapid treatment. Methods We pooled common data elements from six randomised placebo-controlled trials of intravenous rt-PA. Using multivariable logistic regression we assessed the relation of the interval from stroke onset to start of treatment (OTT) on favourable 3-month outcome and on the occurrence of clinically relevant parenchymal haemorrhage. Findings Treatment was started within 360 min of onset of stroke in 2775 patients randomly allocated to rt-PA or placebo. Median age was 68 years, median baseline National Institute of Health Stroke Scale (NIHSS) 11, and median OTT 243 min. Odds of a favourable 3-month outcome increased as OTT decreased (p=0.005). Odds were 2.8 (95% CI 1.8-4.5) for 0-90 min, 1.6 (1.1-2.2) for 91-180 min, 1.4 (1.1-1.9) for 181-270 min, and 1.2 (0.9-1.5) for 271-360 min in favour of the rt-PA group. The hazard ratio for death adjusted for baseline NIHSS was not different from 1.0 for the 0-90, 91-180, and 181-270 min intervals; for 271-360 min it was 1.45 (1.02-2.07). Haemorrhage was seen in 82 (5.9%) rt-PA patients and 15 (1.1%) controls (p<0.0001). Haemorrhage was not associated with OTT but was with rt-PA treatment (p=0.0001) and age (p=0.0002). Interpretation The sooner that rt-PA is given to stroke patients, the greater the benefit, especially if started within 90 min. Our results suggest a potential benefit beyond 3 h, but this potential might come with some risks. C1 NINDS, Clin Trial Grp, Rockville, MD 20852 USA. Med Univ Heidelberg, Heidelberg, Germany. Natl Stroke Res Inst, Melbourne, Vic, Australia. Univ Rome, Rome, Italy. Univ Helsinki, Cent Hosp, FIN-00014 Helsinki, Finland. Tech Univ Dresden, D-8027 Dresden, Germany. Univ Cincinnati, Ctr Stroke Res, Cincinnati, OH 45221 USA. Mayo Clin, Rochester, MN USA. Emory Univ, Sch Med, Atlanta, GA 30322 USA. Univ Texas, Houston Med Ctr, Houston, TX USA. Univ Virginia Hlth Syst, Charlottesville, VA USA. Long Isl Jewish Med Ctr, New Hyde Pk, NY 11042 USA. CUNY Mt Sinai Sch Med, New York, NY 10029 USA. Henry Ford Hlth Syst, Detroit, MI USA. Henry Ford Hosp, Detroit, MI 48202 USA. Univ Calif San Diego, Stroke Ctr, La Jolla, CA 92093 USA. Med Univ S Carolina, Charleston, SC 29425 USA. RP Marler, JR (reprint author), NINDS, Clin Trial Grp, 6001 Execut Blvd,Room 2216, Rockville, MD 20852 USA. EM marlerj@ninds.nih.gov RI DONNAN, GEOFFREY/A-9947-2008; bashzar, salman/R-5748-2016 FU NINDS NIH HHS [N01-NS-02378, N01-NS-02373, N01-NS-02374, N01-NS-02376, N01-NS-02377, N01-NS-02379, N01-NS-02380, N01-NS-02381, N01-NS-02382, N01-NS-2-2343] NR 25 TC 1425 Z9 1512 U1 10 U2 47 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 EI 1474-547X J9 LANCET JI Lancet PD MAR 6 PY 2004 VL 363 IS 9411 BP 768 EP 774 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 801JK UT WOS:000220092000007 PM 15016487 ER PT J AU Jang, YS Lee, MY Choi, SH Kim, MY Chin, H Jeong, SW Kim, IK Kwon, OJ AF Jang, YS Lee, MY Choi, SH Kim, MY Chin, H Jeong, SW Kim, IK Kwon, OJ TI Expression of B/K protein in the hippocampus of kainate-induced rat seizure model SO BRAIN RESEARCH LA English DT Article DE immunohistochemistry; neurotoxicity; endoplasmic reticulum ID ENDOPLASMIC-RETICULUM STRESS; BRAIN; IDENTIFICATION; ISCHEMIA; SYNAPTOTAGMINS; INDUCTION; DOMAIN; GRP78; CELLS; DEATH AB B/K protein is a newly identified member of double C2-like domain protein family. We examined the expression of B/K protein in the hippocampus of kainate-induced rat seizure model. Intraperitoneal injection of kainate increased the immunoreactivity to B/K protein in the CA1 to CA3 of the hippocampus. B/K protein expression began to increase at 6 h, reached the maximum at 12 h, and then returned nearly to the normal level at 72 h after the injection of kainate (12 mg/kg), and it was also dependent on the dose of kainate between 4 and 16 mg/kg. In electron microscopic and subcellular fractionation studies, B/K protein was localized in the endoplasmic reticulum (ER) of the hippocampus. Kainate also induced the expression of BiP, a typical ER stress marker protein, in the hippocampus and the cortex, and it was coexpressed with B/K protein. Moreover, thapsigargin-induced ER stress caused upregulation of B/K protein expression in PC12 cells. In conclusion, our data showing the induction of both B/K protein expression and ER stress response in the hippocampus of kainate seizure model, and ER-specific expression and ER stress-induced expression of B/K strongly suggest the possible role of B/K protein in epileptogenesis or epilepsy-induced neuronal damage. Published by Elsevier B.V. C1 Catholic Univ Korea, Coll Med, Dept Biochem, Seoul 137701, South Korea. Catholic Univ Korea, Coll Med, Dept Anat, Seoul 137701, South Korea. PetaGen Inc, R&D Ctr, Seoul 120140, South Korea. NEI, NIH, Bethesda, MD 20892 USA. RP Kwon, OJ (reprint author), Catholic Univ Korea, Coll Med, Dept Biochem, 505 Banpo Dong, Seoul 137701, South Korea. EM ojkwon@cmc.cuk.ac.kr NR 26 TC 5 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD MAR 5 PY 2004 VL 999 IS 2 BP 203 EP 211 DI 10.1016/j.braines.2003.11.047 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 775ZX UT WOS:000189091500007 PM 14759499 ER PT J AU Fortini, ME AF Fortini, ME TI PAR-1 for the course of neurodegeneration SO CELL LA English DT Editorial Material ID TAU; KINASE; POLARITY; MARK AB The large number of kinases that phosphorylate the microtubule binding protein tau has posed a challenge to understanding their individual roles in turning this protein into a killer of neurons. A study in this issue of Cell (Nishimura et al., 2004) uses an elegant fusion of loss-of-function genetics and transgenic overexpression to make the case that the PAR-1 kinase stands at the head of a temporally ordered series of tau phosphorylations. C1 NCI, Mol Genet Sect, Frederick, MD 21702 USA. RP Fortini, ME (reprint author), NCI, Mol Genet Sect, Bldg 560,Romm 22-12, Frederick, MD 21702 USA. NR 10 TC 4 Z9 4 U1 1 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD MAR 5 PY 2004 VL 116 IS 5 BP 631 EP 632 DI 10.1016/S0092-8674(04)00207-7 PG 2 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 821YQ UT WOS:000221499700001 PM 15006343 ER PT J AU Janicki, SM Tsukamoto, T Salghetti, SE Tansey, WP Sachidanandam, R Prasanth, KV Ried, T Shav-Tal, Y Bertrand, E Singer, RH Spector, DL AF Janicki, SM Tsukamoto, T Salghetti, SE Tansey, WP Sachidanandam, R Prasanth, KV Ried, T Shav-Tal, Y Bertrand, E Singer, RH Spector, DL TI From silencing to gene expression: Real-time analysis in single cells SO CELL LA English DT Article ID POSITION-EFFECT VARIEGATION; FACIOSCAPULOHUMERAL MUSCULAR-DYSTROPHY; HETEROCHROMATIN PROTEIN-1 BINDS; LIVING HUMAN-CELLS; HP1 CHROMO DOMAIN; HISTONE H3; MAMMALIAN-CELLS; RAPID EXCHANGE; DROSOPHILA-MELANOGASTER; LYSINE-9 METHYLATION AB We have developed an inducible system to visualize gene expression at the levels of DNA, RNA and protein in living cells. The system is composed of a 200 copy transgene array integrated into a euchromatic region of chromosome 1 in human U20S cells. The condensed array is heterochromatic as it is associated with HP1, histone H3 methylated at lysine 9, and several histone methyltransferases. Upon transcriptional induction, HP1alpha is depleted from the locus and the histone variant H3.3 is deposited suggesting that histone exchange is a mechanism through which heterochromatin is transformed into a transcriptionally active state. RNA levels at the transcription site increase immediately after the induction of transcription and the rate of synthesis slows over time. Using this system, we are able to correlate changes in chromatin structure with the progression of transcriptional activation allowing us to obtain a real-time integrative view of gene expression. C1 Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA. Utsunomiya Univ, Utsunomiya, Tochigi 321, Japan. NCI, Genet Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Albert Einstein Coll Med, Dept Anat & Struct Biol, Bronx, NY 10461 USA. Albert Einstein Coll Med, Dept Cell Biol, Bronx, NY 10461 USA. CNRS, Inst Genet Mol Montpellier, F-34293 Montpellier, France. RP Spector, DL (reprint author), Cold Spring Harbor Lab, 1 Bungtown Rd, Cold Spring Harbor, NY 11724 USA. EM spector@cshl.edu FU NIBIB NIH HHS [R01 EB002060]; NIGMS NIH HHS [GM067728, GM42694, R01 GM067728] NR 83 TC 396 Z9 407 U1 3 U2 22 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD MAR 5 PY 2004 VL 116 IS 5 BP 683 EP 698 DI 10.1016/S0092-8674(04)00171-0 PG 16 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 821YQ UT WOS:000221499700009 PM 15006351 ER PT J AU Kumar, S Nussinov, R AF Kumar, S Nussinov, R TI Different roles of electrostatics in heat and in cold: Adaptation by citrate synthase SO CHEMBIOCHEM LA English DT Article DE citrate synthases; electrostatic interactions; protein structures; psychrophiles; thermophiles ID SALT BRIDGES; PSYCHROPHILIC ENZYMES; CRYSTAL-STRUCTURE; HYPERTHERMOPHILIC PROTEINS; ANTARCTIC BACTERIUM; PYROCOCCUS-FURIOSUS; ION-PAIRS; STABILITY; THERMOSTABILITY; DEHYDROGENASE AB Electrostatics ploys a major role in,in heat adaptation by thermophilic proteins. Here we ask whether electrostatics similarly contributes to cold adaptation in psychrophilic proteins. We compare the sequences and structures of citrate synthases from the psychrophile Arthobacter Ds2-3R, from chicken, and from the hyperthermophile Pyrococcus furiosus. The three enzymes shore similar packing, burial of nonpolar surface area, and main-chain hydrogen bonding. However, both psychrophilic and hyperthermophilic citrate synthases contain more charged residues, salt bridges, and salt-bridge networks than the mesophile. The electrostatic free-energy contributions toward protein-stability by individual charged residues show greater variabilities in the psychrophilic citrate synthase than in the hyperthermophilic enzyme. The charged residues in the active-site regions of the psychrophile are more destabilizing than those in the active-site regions of the hyperthermophile. In the hyperthermophilic enzyme, salt bridges and their networks largely cluster in the active-site regions and at the. dimer interface. In contrast, in the psychrophile, they are more dispersed throughout the structure. On average, salt bridges and their networks provide greater electrostatic stabilization to the thermophilic citrate synthase at 100degreesC than to the psychrophilic enzyme at 0degreesC. Electrostatics appears to play an important role in both heat and cold adaptation of citrate synthase. However, remarkably, the role may be different in the two types of enzyme: In the hyperthermophile, it may contribute to the integrity of both the protein dimer and the active site by possibly countering conformational disorder at high temperatures. On the other hand, in the psychrophile at low temperatures, electrostatics may contribute to enhance protein solvation and to ensure active-site flexibility. C1 NCI, Basic Res Program, SAIC Frederick Inc, Lab Expt & Computat Biol, Frederick, MD 21702 USA. Tel Aviv Univ, Sackler Fac Med, Dept Human Genet & Mol Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel. RP Nussinov, R (reprint author), NCI, Basic Res Program, SAIC Frederick Inc, Lab Expt & Computat Biol, Bldg 469,Room 151, Frederick, MD 21702 USA. EM ruthn@ncifcrf.gov OI Kumar, Sandeep/0000-0003-2840-6398 FU NCI NIH HHS [N01-CO-12400] NR 59 TC 60 Z9 61 U1 0 U2 7 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1439-4227 J9 CHEMBIOCHEM JI Chembiochem PD MAR 5 PY 2004 VL 5 IS 3 BP 280 EP 290 DI 10.1002/cbic.200300627 PG 11 WC Biochemistry & Molecular Biology; Chemistry, Medicinal SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 802XS UT WOS:000220196800008 PM 14997520 ER PT J AU Ratner, DM Adams, EW Su, J O'Keefe, BR Mrksich, M Seeberger, PH AF Ratner, DM Adams, EW Su, J O'Keefe, BR Mrksich, M Seeberger, PH TI Probing protein-carbohydrate interactions with microarrays of synthetic oligosaccharides SO CHEMBIOCHEM LA English DT Article DE carbohydrate chips; carbohydrates; lectins; microarrays; proteins ID SELF-ASSEMBLED MONOLAYERS; CYANOVIRIN-N; ENVELOPE GLYCOPROTEINS; INACTIVATING PROTEIN; BINDING; ARRAYS; GP120 C1 MIT, Dept Chem, Cambridge, MA 02139 USA. Univ Chicago, Dept Chem, Chicago, IL 60637 USA. Univ Chicago, Inst Biophys Dynam, Chicago, IL 60637 USA. NCI, Mol Targets Discovery Program, Ctr Canc Res, Frederick, MD 21702 USA. RP Seeberger, PH (reprint author), ETH Honggerberg HCI F315, Organ Chem Lab, Wolfgang Pauli Str 10, CH-8093 Zurich, Switzerland. EM seeberger@org.chem.ethz.ch RI Mrksich, Milan/G-2469-2011 NR 28 TC 151 Z9 156 U1 0 U2 13 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1439-4227 J9 CHEMBIOCHEM JI Chembiochem PD MAR 5 PY 2004 VL 5 IS 3 BP 379 EP 382 DI 10.1002/cbic.200300804 PG 4 WC Biochemistry & Molecular Biology; Chemistry, Medicinal SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 802XS UT WOS:000220196800020 PM 14997532 ER PT J AU Calzada, MJ Zhou, L Sipes, JM Zhang, J Krutzsch, HC Iruela-Arispe, ML Annis, DS Mosher, DF Roberts, DD AF Calzada, MJ Zhou, L Sipes, JM Zhang, J Krutzsch, HC Iruela-Arispe, ML Annis, DS Mosher, DF Roberts, DD TI alpha(4)beta(1) integrin mediates selective endothelial cell responses to thrombospondins 1 and 2 in vitro and modulates angiogenesis in vivo SO CIRCULATION RESEARCH LA English DT Article DE adhesion; proliferation; migration; angiogenesis; peptides ID MESSENGER-RNA EXPRESSION; GROWTH-FACTOR; ALPHA(3)BETA(1) INTEGRIN; ALPHA-4-BETA-1 INTEGRIN; PROMOTES ANGIOGENESIS; TUMOR-GROWTH; ADHESION; BREAST; PROLIFERATION; INHIBITION AB We examined the function of alpha(4)beta(1) integrin in angiogenesis and in mediating endothelial cell responses to the angiogenesis modulators, thrombospondin-1 and thrombospondin-2. alpha(4)beta(1) supports adhesion of venous endothelial cells but not of microvascular endothelial cells on immobilized thrombospondin-1, vascular cell adhesion molecule-1, or recombinant N-terminal regions of thrombospondin-1 and thrombospondin-2. Chemotactic activities of this region of thrombospondin-1 and thrombospondin-2 are also mediated by beta(4)beta(1), whereas antagonism of fibroblast growth factor-2-stimulated chemotaxis is not mediated by this region. Immobilized N-terminal regions of thrombospondin-1 and thrombospondin-2 promote endothelial cell survival and proliferation in an alpha(4)beta(1)-dependent manner. Soluble alpha(4)beta(1) antagonists inhibit angiogenesis in the chick chorioallantoic membrane and neovascularization of mouse muscle explants. The latter inhibition is thrombospondin-1-dependent and not observed in explants from thrombospondin-1 (-/-) mice. Antagonizing alpha(4)beta(1) may in part block proangiogenic activities of thrombospondin-1 and thrombospondin-2, because N-terminal regions of thrombospondin-1 and thrombospondin-2 containing the alpha(4)beta(1) binding sequence stimulate angiogenesis in vivo. Therefore, alpha(4)beta(1) is an important endothelial cell receptor for mediating motility and proliferative responses to thrombospondins and for modulation of angiogenesis. C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Dept Mol Cell & Dev Biol, Los Angeles, CA USA. Univ Wisconsin, Dept Med, Madison, WI USA. RP Roberts, DD (reprint author), NCI, Pathol Lab, NIH, Bldg 10,Room 2A33,10 Ctr Dr, Bethesda, MD 20892 USA. EM droberts@helix.nih.gov RI Roberts, David/A-9699-2008; Zhang, Jiaying/M-4845-2016 OI Roberts, David/0000-0002-2481-2981; Zhang, Jiaying/0000-0003-2725-1259 FU NCPDCID CDC HHS [2R01NIH-NCI-CA-6562-]; NHLBI NIH HHS [HL54462, HL56396] NR 49 TC 64 Z9 67 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD MAR 5 PY 2004 VL 94 IS 4 BP 462 EP 470 DI 10.1161/01.RES.0000115555.05668.93 PG 9 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 800NF UT WOS:000220034300008 PM 14699013 ER PT J AU Korn, ED AF Korn, ED TI The discovery of unconventional myosins: Serendipity or luck? SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HEAVY-CHAIN KINASE; ACTIVATED LIPOPROTEIN LIPASE; ACTIN-BASED MOTILITY; ACANTHAMOEBA MYOSIN; F-ACTIN; PHOSPHORYLATION SITES; MG2&-ATPASE ACTIVITY; COFACTOR PROTEIN; CLEARING FACTOR; TAIL DOMAINS C1 NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Korn, ED (reprint author), NHLBI, Cell Biol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. EM edk@nih.gov NR 70 TC 3 Z9 3 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 5 PY 2004 VL 279 IS 10 BP 8517 EP 8525 DI 10.1074/jbc.X300010200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 778XD UT WOS:000189265900001 PM 14724268 ER PT J AU Cha, MK Kim, WC Lim, CJ Kim, K Kim, IH AF Cha, MK Kim, WC Lim, CJ Kim, K Kim, IH TI Escherichia coli periplasmic thiol peroxidase acts as lipid hydroperoxide peroxidase and the principal antioxidative function during anaerobic growth SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID OXIDATIVE STRESS; PEROXIREDOXINS; PROTEINS; FAMILY; PURIFICATION; MECHANISM; REDUCTASE; PATHWAYS AB To clarify the enzymatic property of Escherichia coli periplasmic thiol peroxidase (p20), the specific peroxidase activity toward peroxides was compared with other bacterial thiol peroxidases. p20 has the most substrate preference and peroxidase activity toward organic hydroperoxide. Furthermore, p20 exerted the most potent lipid peroxidase activity. Despite that the mutation of p20 caused the highest susceptibility toward organic hydroperoxide and heat stress, the cellular level of p20 did not respond to the exposure of oxidative stress. Expression level of p20 during anaerobic growth was sustained at the similar to50% level compared with that of the aerobic growth. Viability of aerobic p20Delta without glucose was reduced to the similar to65% level of isogenic strains, whereas viability of aerobic p20Delta with 0.5% glucose supplement was sustained. The deletion of p20 resulted in a gradual loss of the cell viability during anaerobic growth. At the stationary phase, the viability of p20Delta was down to similar to10% level of parent strains. An analysis of the protein carbonyl contents of p20Delta as a marker for cellular oxidation indicates that severe reduction of viability of anaerobic p20Delta was caused by cumulative oxidative stress. P20Delta showed hypersensitivity toward membrane-soluble organic hydroperoxides. An analysis of protein carbonyl and lipid hydroperoxide contents in the membrane of the stress-imposed p20Delta demonstrates that the severe reduction of viability was caused by cumulative oxidative stress on the membrane. Taken together, present data uncover in vivo function for p20 as a lipid hydroperoxide peroxidase and demonstrate that, as the result, p20 acts as the principal antioxidant in the anaerobic habitats. C1 Paichai Univ, Dept Biochem, Taejon 302735, South Korea. NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. Kangweon Natl Univ, Dept Biochem, Chunchon 200701, South Korea. Chonnam Natl Univ, Dept Food & Nutr, Kwangjoo 50075, South Korea. RP Kim, IH (reprint author), Paichai Univ, Dept Biochem, 439-6 Doma 2 Dong, Taejon 302735, South Korea. EM ihkim@mail.paichai.ac.kr NR 30 TC 40 Z9 43 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 5 PY 2004 VL 279 IS 10 BP 8769 EP 8778 DI 10.1074/jbc.M312388200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 778XD UT WOS:000189265900031 PM 14676195 ER PT J AU Lewis, J Burstein, E Reffey, SB Bratton, SB Roberts, AB Duckett, CS AF Lewis, J Burstein, E Reffey, SB Bratton, SB Roberts, AB Duckett, CS TI Uncoupling of the signaling and caspase-inhibitory properties of X-linked inhibitor of apoptosis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NF-KAPPA-B; SERINE-PROTEASE OMI/HTRA2; STRUCTURAL BASIS; CYTOCHROME-C; BIR DOMAIN; BACULOVIRAL-INHIBITOR; ENDOTHELIAL-CELLS; NMR STRUCTURE; XIAP; IAP AB In addition to its well described function as an enzymatic inhibitor of specific caspases, X-linked inhibitor of apoptosis (X-linked IAP or XIAP) can function as a cofactor in Smad, NF-kappaB, and JNK signaling pathways. However, caspases themselves have been shown to regulate the activity of a number of signaling cascades, raising the possibility that the effect of XIAP in these pathways is indirect. Here we examine this question by introducing point mutations in XIAP predicted to disrupt the ability of the molecule to bind to and inhibit caspases. We show that whereas these mutant variants of XIAP lost caspase-inhibitory activity, they maintained their ability to activate Smad, NF-kappaB, and JNK signaling pathways. Indeed, the signaling properties of the molecule were mapped to domains not directly involved in caspase binding and inhibition. The activation of NF-kappaB by XIAP was dependent on the E3 ubiquitin ligase activity of the RING domain. On the other hand, the ability of XIAP to activate Smad-dependent signaling was mapped to the third baculoviral IAP repeat (BIR) and loop regions of the molecule. Thus, the antiapoptotic and signaling properties of XIAP can be uncoupled. C1 Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA. Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI 48109 USA. Sci Applicat Int Corp, Conressionally Directed Med Res Program, Biomed Technol Div, MCMRPLF, Ft Detrick, MD 21702 USA. Univ Texas, Coll Pharm, Ctr Mol & Cellular Toxicol, Austin, TX 78718 USA. NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bethesda, MD 20892 USA. RP Duckett, CS (reprint author), Rm 5315,1301 Catherine, Ann Arbor, MI 48109 USA. EM colind@umich.edu RI Burstein, Ezra/B-7247-2016 OI Burstein, Ezra/0000-0003-4341-6367 NR 51 TC 71 Z9 78 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 5 PY 2004 VL 279 IS 10 BP 9023 EP 9029 DI 10.1074/jbc.M312891200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 778XD UT WOS:000189265900062 PM 14701799 ER PT J AU Ye, RQ Goodarzi, AA Kurz, EU Saito, S Higashimoto, Y Lavin, MF Appella, E Anderson, CW Lees-Miller, SP AF Ye, RQ Goodarzi, AA Kurz, EU Saito, S Higashimoto, Y Lavin, MF Appella, E Anderson, CW Lees-Miller, SP TI The isoflavonoids genistein and quercetin activate different stress signaling pathways as shown by analysis of site-specific phosphorylation of ATM, p53 and histone H2AX SO DNA REPAIR LA English DT Article DE p53; genistein; quercetin; isoflavonoid; DNA damage; phosphorylation ID DOUBLE-STRAND BREAKS; HUMAN-MELANOMA CELLS; ATAXIA-TELANGIECTASIA; PROTEIN-KINASE; DNA-DAMAGE; POSTTRANSLATIONAL MODIFICATIONS; IONIZING-RADIATION; CANCER CELLS; IN-VITRO; FLAVONOIDS AB The ataxia-telangiectasia mutated (ATM) protein kinase is activated in response to ionizing radiation (IR) and activates downstream DNA-damage signaling pathways. Although the role of ATM in the cellular response to ionizing radiation has been well characterized, its role in response to other DNA-damaging agents is less well defined. We previously showed that genistein, a naturally occurring isoflavonoid, induced increased ATM protein kinase activity, ATM-dependent phosphorylation of p53 on serine 15 and activation of the DNA-binding properties of p53. Here. we show that genistein also induces phosphorylation of p53 at serines 6, 9, 20,46, and 392, and that genistein-induced accumulation and phosphorylation of p53 is reduced in two ATM-deficient human cell lines. Also, we show that genistein induces phosphorylation of ATM on serine 1981 and phosphorylation of histone H2AX on serine 139. The related bioflavonoids, daidzein and biochanin A, did not induce either phosphorylation of p53 or ATM at these sites. Like genistein, quercetin induced phosphorylation of ATM on serine 198 1, and ATM-dependent phosphorylation of histone H2AX on serine 139; however, p53 accumulation and phosphorylation on serines 6, 9, 15, 20, 46, and 392 occurred in ATM-deficient cells, indicating that ATM is not required for quercetin-induced phosphorylation of p53. Our data suggest that genistein and quercetin induce different DNA-damage induced signaling pathways that, in the case of genistein, are highly ATM-dependent but, in the case of quercetin, may be ATM-dependent only for some downstream targets. (C) 2003 Elsevier B.V. All rights reserved. C1 Univ Calgary, Dept Biochem & Mol Biol, Calgary, AB T2N 4N1, Canada. NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. PO Royal Brisbane Hosp, Queensland Inst Med Res, Brisbane, Qld 4029, Australia. Brookhaven Natl Lab, Dept Biol, Upton, NY 11973 USA. RP Lees-Miller, SP (reprint author), Univ Calgary, Dept Biochem & Mol Biol, 3330 Hosp Dr,NW, Calgary, AB T2N 4N1, Canada. EM leesmill@ucalgary.ca RI Lavin, Martin/F-5961-2014 OI Lavin, Martin/0000-0002-5940-4769 NR 44 TC 46 Z9 50 U1 0 U2 14 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1568-7864 J9 DNA REPAIR JI DNA Repair PD MAR 4 PY 2004 VL 3 IS 3 BP 235 EP 244 DI 10.1016/j.dnarep.2003.10.014 PG 10 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 776BD UT WOS:000189094400004 PM 15177039 ER PT J AU McCulloch, SD Kokoska, RJ Masutani, C Iwai, S Hanaoka, F Kunkel, TA AF McCulloch, SD Kokoska, RJ Masutani, C Iwai, S Hanaoka, F Kunkel, TA TI Preferential cis-syn thymine dimer bypass by DNA polymerase eta occurs with biased fidelity SO NATURE LA English DT Article ID LESION-BYPASS; XERODERMA-PIGMENTOSUM; CRYSTAL-STRUCTURE; ERROR-PRONE; POL-ETA; YEAST; SITE; GENE; SPECIFICITY; MUTAGENESIS AB Human DNA polymerase eta (Pol eta) modulates susceptibility to skin cancer by promoting DNA synthesis past sunlight-induced cyclobutane pyrimidine dimers that escape nucleotide excision repair (NER)(1,2). Here we have determined the efficiency and fidelity of dimer bypass. We show that Pol eta copies thymine dimers and the flanking bases with higher processivity than it copies undamaged DNA, and then switches to less processive synthesis. This ability of Pol eta to sense the dimer location as synthesis proceeds may facilitate polymerase switching before and after lesion bypass. Pol eta bypasses a dimer with low fidelity and with higher error rates at the 3' thymine than at the 5' thymine. A similar bias is seen with Sulfolobus solfataricus DNA polymerase 4, which forms a Watson-Crick base pair at the 3' thymine of a dimer but a Hoogsteen base pair at the 5' thymine (ref. 3). Ultraviolet-induced mutagenesis is also higher at the 3' base of dipyrimidine sequences(4-6). Thus, in normal people and particularly in individuals with NER-defective xeroderma pigmentosum who accumulate dimers, errors made by Pol eta uring dimer bypass could contribute to mutagenesis and skin cancer. C1 NIEHS, Genet Mol Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA. NIEHS, Struct Biol Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA. Osaka Univ, Grad Sch Frontier Biosci, Suita, Osaka 5650871, Japan. Japan Sci & Technol Corp, CREST, Suita, Osaka 5650871, Japan. Osaka Univ, Grad Sch Engn Sci, Div Chem, Osaka 5608531, Japan. RIKEN, Discovery Res Inst, Wako, Saitama 3510198, Japan. RP Kunkel, TA (reprint author), NIEHS, Genet Mol Lab, NIH, DHHS, POB 12233, Res Triangle Pk, NC 27709 USA. EM kunkel@niehs.nih.gov RI Masutani, Chikahide/I-6160-2014 NR 28 TC 174 Z9 179 U1 1 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAR 4 PY 2004 VL 428 IS 6978 BP 97 EP 100 DI 10.1038/nature02352 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 780GK UT WOS:000189363800043 PM 14999287 ER PT J AU Beauchamp, MS Lee, KE Argall, BD Martin, A AF Beauchamp, MS Lee, KE Argall, BD Martin, A TI Integration of auditory and visual information about objects in superior temporal sulcus SO NEURON LA English DT Article ID HUMAN CEREBRAL-CORTEX; HUMAN NEURAL SYSTEMS; MACAQUE MONKEY; HUMAN BRAIN; AUDIOVISUAL INTEGRATION; MANIPULATABLE OBJECTS; HEMISPHERIC LESIONS; CROSSMODAL BINDING; PROCESSING STREAMS; PREFRONTAL CORTEX AB Two categories of objects in the environment-animals and man-made manipulable objects (tools)-are easily recognized by either their auditory or visual features. Although these features differ across modalities, the brain integrates them into a coherent percept. In three separate fMRI experiments, posterior superior temporal sulcus and middle temporal gyrus (pSTS/MTG) fulfilled objective criteria for an integration site. pSTS/MTG showed signal increases in response to either auditory or visual stimuli and responded more to auditory or visual objects than to meaningless (but complex) control stimuli. pSTS/MTG showed an enhanced response when auditory and visual object features were presented together, relative to presentation in a single modality. Finally, pSTS/MTG responded more to object identification than to other components of the behavioral task. We suggest that pSTS/MTG is specialized for integrating different types of information both within modalities (e.g., visual form, visual motion) and across modalities (auditory and visual). C1 NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. RP Beauchamp, MS (reprint author), NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. EM mbeauchamp@nih.gov RI Argall, Brenna/G-2543-2011; martin, alex/B-6176-2009 NR 90 TC 372 Z9 373 U1 5 U2 31 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD MAR 4 PY 2004 VL 41 IS 5 BP 809 EP 823 DI 10.1016/S0896-6273(04)00070-4 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 821KD UT WOS:000221458200015 PM 15003179 ER PT J AU Fidani, L Goulas, A Crook, R Petersen, RC Tangalos, E Kotsis, A Hardy, J AF Fidani, L Goulas, A Crook, R Petersen, RC Tangalos, E Kotsis, A Hardy, J TI An association study of the cholesteryl ester transfer protein TaqI B polymorphism with late onset Alzheimer's disease SO NEUROSCIENCE LETTERS LA English DT Article DE Alzheimer's disease; cholesteryl ester transfer protein; apolipoprotein E; lipoprotein lipase; polymorphism; genetics ID LIPOPROTEIN-LIPASE; COMMON VARIANT; GENE; RISK; ALLELE; HEART; BRAIN AB Cholesteryl ester transfer protein (CETP) is reportedly able to affect the amount of cholesterol available for deposition and/or removal from peripheral tissues, in its capacity to mediate the transfer of cholesterol from high density lipoprotein (HDL) to very low density lipoprotein, in exchange for triacylglycerols from the latter. The TaqI B polymorphism of the human CETP gene has been associated with decreased CETP mass and an increase in HDL-cholesterol. While many studies have addressed the atherogenic or anti-atherogenic potential of this polymorphism, little is known about its effect on neurodegeneration, despite the fact that CETP is expressed in the brain and the disturbance of cholesterol homeostasis appears to be an important factor in the pathogenesis of Alzheimer's disease (AD). In this report, we have compared the distribution of the TaqI B polymorphism in an independent population of 102 clinically diagnosed late onset AD patients and a spousal control group of 97 individuals. We have also examined the possible interaction between this polymorphism and two other polymorphisms suspected of affecting cholesterol flux, namely apolipoprotein E APOE epsilon4, and lipoprotein lipase LPLS447X. No statistically significant differences have emerged with respect to either genotype or allele frequencies between the AD and control populations. CETP TaqI B did not interact significantly with either APOE epsilon4 or LPLS447X, in this study. (C) 2003 Elsevier Ireland Ltd. All rights reserved. C1 Aristotle Univ Thessaloniki, Sch Med, Dept Gen Biol, Thessaloniki 54124, Greece. Aristotle Univ Thessaloniki, Sch Med, Dept Pharmacol, Thessaloniki 54124, Greece. Mayo Clin, Dept Neurol, Rochester, MN 55905 USA. Mayo Clin, Dept Community Med, Rochester, MN 55905 USA. Mayo Clin, Dept Neurol, Rochester, MN 55905 USA. NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. Reta Lila Weston Inst Neurol, London WC2, England. RP Fidani, L (reprint author), 6 D Gounari Str, Thessaloniki 54621, Greece. EM lfidani@med.auth.gr RI Hardy, John/C-2451-2009 FU NIA NIH HHS [AG 06786, AG 16574, AG 21013] NR 19 TC 20 Z9 21 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD MAR 4 PY 2004 VL 357 IS 2 BP 152 EP 154 DI 10.1016/j.neulet.2003.11.071 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 780KZ UT WOS:000189381000019 PM 15036597 ER PT J AU Williams, CF Klinzman, D Yamashita, TE Xiang, JH Polgreen, PM Rinaldo, C Liu, CL Phair, J Margolick, JB Zdunek, D Hess, G Stapleton, JT AF Williams, CF Klinzman, D Yamashita, TE Xiang, JH Polgreen, PM Rinaldo, C Liu, CL Phair, J Margolick, JB Zdunek, D Hess, G Stapleton, JT TI Persistent GB virus C infection and survival in HIV-infected men SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID HEPATITIS-G VIRUS; MULTICENTER AIDS COHORT; C/HEPATITIS-G VIRUS; DISEASE PROGRESSION; RNA; COINFECTION; HEMOPHILIA; TRANSMISSION; ASSOCIATION; PREVALENCE AB BACKGROUND: GB virus C (GBV-C), which is not known to be pathogenic in humans, replicates in lymphocytes, inhibits the replication of human immunodeficiency virus (HIV) in vitro, and has been associated with a decreased risk of death among HIV-positive persons in some, but not all, studies. Previous studies did not control for differences in the duration of HIV or GBV-C infection. METHODS: We evaluated 271 men who were participants in the Multicenter Acquired Immunodeficiency Syndrome Cohort Study for GBV-C viremia (by means of a reverse-transcriptase-polymerase-chain-reaction assay) or E2 antibody (by means of an enzyme-linked immunosorbent assay) 12 to 18 months after seroconversion to positivity for HIV (the early visit); a subgroup of 138 patients was also evaluated 5 to 6 years after HIV seroconversion (the late visit). RESULTS: GBV-C infection was detected in 85 percent of men with HIV seroconversion on the basis of the presence of E2 antibody (46 percent) or GBV-C RNA (39 percent). Only one man acquired GBV-C viremia between the early and the late visit, but 9 percent of men had clearance of GBV-C RNA between these visits. GBV-C status 12 to 18 months after HIV seroconversion was not significantly associated with survival; however, men without GBV-C RNA 5 to 6 years after HIV seroconversion were 2.78 times as likely to die as men with persistent GBV-C viremia (95 percent confidence interval, 1.34 to 5.76; P=0.006). The poorest prognosis was associated with the loss of GBV-C RNA (relative hazard for death as compared with men with persistent GBV-C RNA, 5.87; P=0.003). CONCLUSIONS: GBV-C viremia was significantly associated with prolonged survival among HIV-positive men 5 to 6 years after HIV seroconversion, but not at 12 to 18 months, and the loss of GBV-C RNA by 5 to 6 years after HIV seroconversion was associated with the poorest prognosis. Understanding the mechanisms of interaction between GBV-C and HIV may provide insight into the progression of HIV disease. C1 NIAID, Epidemiol Branch, Div AIDS, Bethesda, MD 20892 USA. Univ Iowa, Iowa City, IA USA. Iowa City Vet Affairs Med Ctr, Iowa City, IA USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA. Univ Calif Los Angeles, Los Angeles, CA USA. Northwestern Univ, Howard Brown Hlth Ctr, Chicago, IL 60611 USA. Roche Diagnost, Penzberg, Germany. Roche Diagnost, Mannheim, Germany. RP Stapleton, JT (reprint author), UIHC, GH, SW 34-P, Iowa City, IA 52242 USA. EM jack-stapleton@uiowa.edu FU NCRR NIH HHS [5-M01-RR-00722]; NIAID NIH HHS [AI 250478, AI 27661, UO1-AI-35039, UO1-AI-35040, UO1-AI-35041, UO1-AI-35042, UO1-AI-35043, UO1-AI-37613, UO1-AI-37984] NR 36 TC 174 Z9 181 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 4 PY 2004 VL 350 IS 10 BP 981 EP 990 DI 10.1056/NEJMoa030107 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 780GH UT WOS:000189363600006 PM 14999110 ER PT J AU Balow, JE Austin, HA AF Balow, JE Austin, HA TI Maintenance therapy for lupus nephritis - Something old, something new SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID CONTROLLED TRIAL; CYCLOPHOSPHAMIDE; PREDNISONE C1 NIDDKD, Kidney Dis Sect, Bethesda, MD 20892 USA. RP Balow, JE (reprint author), NIDDKD, Kidney Dis Sect, Bethesda, MD 20892 USA. NR 9 TC 19 Z9 26 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 4 PY 2004 VL 350 IS 10 BP 1044 EP 1046 DI 10.1056/NEJMe048010 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 780GH UT WOS:000189363600014 PM 14999117 ER PT J AU Hortin, GL AF Hortin, GL TI Prolactinomas SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID MACROPROLACTIN C1 NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Hortin, GL (reprint author), NIH, Ctr Clin, Bethesda, MD 20892 USA. EM ghortin@mail.cc.nih.gov NR 4 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 4 PY 2004 VL 350 IS 10 BP 1055 EP 1055 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 780GH UT WOS:000189363600027 ER PT J AU Bruce, ML Ten Have, TR Reynolds, CF Katz, II Schulberg, HC Mulsant, BH Brown, GK McAvay, GJ Pearson, JL Alexopoulos, GS AF Bruce, ML Ten Have, TR Reynolds, CF Katz, II Schulberg, HC Mulsant, BH Brown, GK McAvay, GJ Pearson, JL Alexopoulos, GS TI Reducing suicidal ideation and depressive symptoms in depressed older primary care patients - A randomized controlled trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID LATE-LIFE DEPRESSION; LOGISTIC-REGRESSION MODELS; IMPROVING PRIMARY-CARE; BINARY RESPONSE DATA; MAJOR DEPRESSION; GERIATRIC DEPRESSION; CONSENSUS STATEMENT; QUALITY IMPROVEMENT; MINOR DEPRESSION; TERM TREATMENT AB Context Suicide rates are highest in late life; the majority of older adults who die by suicide have seen a primary care physician in preceding months. Depression is the strongest risk factor for late-life suicide and for suicide's precursor, suicidal ideation. Objective To determine the effect of a primary care intervention on suicidal ideation and depression in older patients. Design and Setting Randomized controlled trial known as PROSPECT (Prevention of Suicide in Primary Care Elderly: Collaborative Trial) with patient recruitment from 20 primary care practices in New York City, Philadelphia, and Pittsburgh regions, May 1999 through August 2001. Participants Two-stage, age-stratified (60-74, greater than or equal to75 years) depression screening of randomly sampled patients; enrollment included patients who screened positive and a random sample of screened negative patients. This analysis included patients with a depression diagnosis (N=598). Intervention Treatment guidelines tailored for the elderly with care management compared with usual care. Main Outcome Measures Assessment of suicidal ideation and depression severity at baseline, 4 months, 8 months, and 12 months. Results Rates of suicidal ideation declined faster (P=.01) in intervention patients compared with usual care patients; at 4 months, in the intervention group, raw rates of suicidal ideation declined 12.9% points (29.4% to 16.5%) compared with 3.0% points (20.1% to 17.1% in usual care [P=.01]). Among patients reporting suicidal ideation, resolution of ideation was faster among intervention patients (P=.03); differences peaked at 8 months (70.7% vs 43.9% resolution; P=.005). Intervention patients had a more favorable course of depression in both degree and speed of symptom reduction; group difference peaked at 4 months. The effects on depression were not significant among,, patients with minor depression unless suicidal ideation was present. Conclusions Evidence of the intervention's effectiveness in community-based primary care with a heterogeneous sample of depressed patients introduces new challenges related to its sustainability and dissemination. The intervention's effectiveness in reducing suicidal ideation, regardless of depression severity, reinforces its role as a prevention strategy to reduce risk factors for suicide in late life. C1 Univ Pittsburgh, Dept Psychiat, WPIC, Sch Med, Pittsburgh, PA 15213 USA. Cornell Univ, Weill Med Coll, Dept Psychiat, White Plains, NY USA. Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Mental Illness Res Educ & Clin Ctr, Philadelphia, PA USA. VA Pittsburgh Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA. NIMH, Div Intervent & Serv Res, Bethesda, MD 20892 USA. RP Reynolds, CF (reprint author), Univ Pittsburgh, Dept Psychiat, WPIC, Sch Med, Room 1135-E,3811 Ohara St, Pittsburgh, PA 15213 USA. EM ReynoldsCF@msx.upmc.edu FU NIMH NIH HHS [K01 MH01613, K02 MH01634, P30 MH52129, P30 MH52247, P30 MH68638, R01 MH59366, R01 MH59380, R01 MH59381] NR 76 TC 553 Z9 560 U1 5 U2 39 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAR 3 PY 2004 VL 291 IS 9 BP 1081 EP 1091 DI 10.1001/jama.291.9.1081 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 780AQ UT WOS:000189348900025 PM 14996777 ER PT J AU Nienborg, H Bridge, H Parker, AJ Cumming, BG AF Nienborg, H Bridge, H Parker, AJ Cumming, BG TI Receptive field size in V1 neurons limits acuity for perceiving disparity modulation SO JOURNAL OF NEUROSCIENCE LA English DT Article DE vision; binocular disparity; awake behaving macaque; striate cortex; stereopsis; receptive field size ID BINOCULAR DEPTH DISCRIMINATION; TEMPORAL-FREQUENCY-SELECTIVITY; CATS STRIATE CORTEX; CORTICAL AREA V1; SIMPLE CELLS; ORIENTATION DISPARITY; HORIZONTAL DISPARITY; NEURAL MECHANISM; 3D ORIENTATION; ENERGY MODELS AB Disparity selectivity in the striate cortex has generally been studied with uniform disparity fields covering the receptive field (RF). In four awake behaving monkeys, we quantitatively characterized the spatial three-dimensional structure of 55 V1 RFs using random dot stereograms in which disparity varied as a sinusoidal function of vertical position ("corrugations"). At low spatial frequencies, this produced a modulation in neuronal firing at the temporal frequency of the stimulus. As the spatial frequency increased, the modulation reduced. The mean response rate changed little and was close to that produced by a uniform stimulus at the mean disparity of the corrugation. In 48 of 55 (91%) neurons, the modulation strength was a lowpass function of spatial frequency. These results are compatible with a response determined only by the weighted mean of the disparities of the dots (the weights being set by the RF envelope) and suggest that there is no disparity-based surround inhibition or selectivity for disparity gradients. This simple weighting scheme predicts a relationship between RF size and the high-frequency cutoff. Comparison with independent measurements of RF size was compatible with this. All of this behavior closely matches the binocular energy model. The mean cutoff frequency, 0.5 cycles per degree, is similar to equivalent measures of decline in human psychophysical sensitivity for such depth corrugations as a function of frequency (Tyler, 1974; Prince and Rogers, 1998; Banks et al., 2004). This suggests that human cyclopean acuity for disparity modulations is limited by the selectivity of V1 neurons. This in turn is primarily limited by the RF size, because we find no sensitivity for disparity gradients or other disparity differences within the RFs. C1 NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. Univ Oxford, Physiol Lab, Oxford OX1 3PT, England. RP Nienborg, H (reprint author), 49-2A50 Convent Dr, Bethesda, MD 20892 USA. EM hn@lsr.nei.nih.gov RI Parker, Andrew/I-7867-2013; OI Parker, Andrew/0000-0001-5800-0407; Bridge, Holly/0000-0002-8089-6198 NR 46 TC 47 Z9 48 U1 0 U2 3 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAR 3 PY 2004 VL 24 IS 9 BP 2065 EP 2076 DI 10.1523/JNEUROSCI.3887-03.2004 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 780PX UT WOS:000189391500001 PM 14999058 ER PT J AU Lei, SB McBain, CJ AF Lei, SB McBain, CJ TI Two loci of expression for long-term depression at hippocampal mossy fiber-interneuron synapses SO JOURNAL OF NEUROSCIENCE LA English DT Article DE AMPA; depression; hippocampus; interneuron; synapse; glutamate ID AMPA RECEPTOR TRAFFICKING; MULTIVESICULAR RELEASE; SYNAPTIC-TRANSMISSION; TRANSMITTER RELEASE; CEREBELLAR STELLATE; QUANTAL ANALYSIS; RAT HIPPOCAMPUS; NEURONS; MECHANISMS; PLASTICITY AB Two distinct forms of long-term depression (LTD) exist at mossy fiber synapses between dentate gyrus granule cells and hippocampal CA3 stratum lucidum interneurons. Although induction of each form of LTD requires an elevation of postsynaptic intracellular Ca2+, at Ca2+-impermeable AMPA receptor (CI-AMPAR) synapses, induction is NMDA receptor (NMDAR) dependent, whereas LTD at Ca2+-permeable AMPA receptor (CP-AMPAR) synapses is NMDAR independent. However, the expression locus of either form of LTD is not known. Using a number of criteria, including the coefficient of variation, paired-pulse ratio, AMPA-NMDA receptor activity, and the low-affinity AMPAR antagonist gamma-D-glutamyl-glycine, we demonstrate that LTD expression at CP-AMPAR synapses is presynaptic and results from reduced transmitter release, whereas LTD expression at CI-AMPAR synapses is postsynaptic. The N-ethylmaleimide-sensitive fusion protein-AP2-clathrin adaptor protein 2 inhibitory peptide pep2m occluded LTD expression at CI-AMPAR synapses but not at CP-AMPAR synapses, confirming that CI-AMPAR LTD involves postsynaptic AMPAR trafficking. Thus, mossy fiber innervation of CA3 stratum lucidum interneurons occurs via two parallel systems targeted to either Ca2+-permeable or Ca2+-impermeable AMPA receptors, each with a distinct expression locus for long-term synaptic plasticity. C1 NICHHD, Lab Cellular & Synapt Neurophysiol, NIH, Bethesda, MD 20892 USA. RP NICHHD, Lab Cellular & Synapt Neurophysiol, NIH, Room 5A72,Bldg 49,Convent Dr, Bethesda, MD 20892 USA. EM mcbainc@mail.nih.gov RI yu, yan/C-2322-2012 NR 61 TC 62 Z9 65 U1 0 U2 0 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD MAR 3 PY 2004 VL 24 IS 9 BP 2112 EP 2121 DI 10.1523/JNEUROSCI.4645-03.2004 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 780PX UT WOS:000189391500005 PM 14999062 ER PT J AU Laskey, WK Selzer, F Cohen, H Holmes, D Wilensky, R Williams, D Detre, K AF Laskey, WK Selzer, F Cohen, H Holmes, D Wilensky, R Williams, D Detre, K CA NHLBI Dynamic Registry TI Temporal variation in fatal percutaneous coronary intervention outcomes: A report from the National Heart, Lung, and Blood Institute Dynamic Registry SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 54th Annual Scientific Session of the American-College-of-Cardiology CY MAR 07-10, 2004 CL New Orleans, LA SP Amer Coll Cardiol C1 Natl Naval Med Res Inst, NHLBI, Dyanm Registry, Bethesda, MD USA. Univ Pittsburgh, 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 3 PY 2004 VL 43 IS 5 SU A BP 97A EP 97A DI 10.1016/S0735-1097(04)90404-4 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 780NW UT WOS:000189388500406 ER PT J AU Tocchetti, CG Katori, T Zaccolo, M Mancardi, D Belardi, DF Miranda, KM Wink, DA Kass, DA Paolocci, N AF Tocchetti, CG Katori, T Zaccolo, M Mancardi, D Belardi, DF Miranda, KM Wink, DA Kass, DA Paolocci, N TI The HNO/nitric oxide donor Angeli's salt enhances myocyte contractility in a PKA-dependent manner SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 54th Annual Scientific Session of the American-College-of-Cardiology CY MAR 07-10, 2004 CL New Orleans, LA SP Amer Coll Cardiol C1 Johns Hopkins Univ, Baltimore, MD USA. NIH, Bethesda, MD 20892 USA. RI Miranda, Katrina/B-7823-2009; Zaccolo, Manuela/B-3802-2011 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 3 PY 2004 VL 43 IS 5 SU A BP 156A EP 156A DI 10.1016/S0735-1097(04)90661-4 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 780NW UT WOS:000189388500663 ER PT J AU Dyke, CK Kellman, P Ingkanisorn, WP Rhoads, KL Aletras, AH Arai, AE AF Dyke, CK Kellman, P Ingkanisorn, WP Rhoads, KL Aletras, AH Arai, AE TI Clinical characteristics and prevalence of pericardial effusion using cardiac magnetic resonance imaging SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 54th Annual Scientific Session of the American-College-of-Cardiology CY MAR 07-10, 2004 CL New Orleans, LA SP Amer Coll Cardiol C1 NHLBI, 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 3 PY 2004 VL 43 IS 5 SU A BP 202A EP 202A DI 10.1016/S0735-1097(04)90860-1 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 780NW UT WOS:000189388500862 ER PT J AU Shizukuda, Y Sachdev, V Brenneman, CL Birdsall, CW Fananapazir, L Plehn, JF AF Shizukuda, Y Sachdev, V Brenneman, CL Birdsall, CW Fananapazir, L Plehn, JF TI Role of left atrial contractile function in functional capacity of patients with hypertrophic nonobstructive cardiomyopathy SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 54th Annual Scientific Session of the American-College-of-Cardiology CY MAR 07-10, 2004 CL New Orleans, LA SP Amer Coll Cardiol C1 NHLBI, 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 3 PY 2004 VL 43 IS 5 SU A BP 216A EP 216A DI 10.1016/S0735-1097(04)90917-5 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 780NW UT WOS:000189388500919 ER PT J AU Katori, T Tocchetti, CG Miranda, KM Champion, HC Fukuto, JM Wink, DA Kass, DA Paolocci, N AF Katori, T Tocchetti, CG Miranda, KM Champion, HC Fukuto, JM Wink, DA Kass, DA Paolocci, N TI The novel organic nitroxyl donor, isopropylamine/nitric oxide exerts beta-independent positive inotropy/lusitropy in failing hearts SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 54th Annual Scientific Session of the American-College-of-Cardiology CY MAR 07-10, 2004 CL New Orleans, LA SP Amer Coll Cardiol C1 Johns Hopkins Univ, Baltimore, MD USA. NIH, Bethesda, MD 20892 USA. RI Miranda, Katrina/B-7823-2009 NR 0 TC 1 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 3 PY 2004 VL 43 IS 5 SU A BP 218A EP 218A DI 10.1016/S0735-1097(04)90925-4 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 780NW UT WOS:000189388500927 ER PT J AU Deans, KJ Minneci, PC Banks, SM Solomon, MA MacGillivray, TE Hoffman, WD Natanson, C Vlahakes, GJ AF Deans, KJ Minneci, PC Banks, SM Solomon, MA MacGillivray, TE Hoffman, WD Natanson, C Vlahakes, GJ TI Coronary artery bypass grafting without cardiopulmonary bypass increases survival rate and decreases morbidity: A meta-analysis SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 54th Annual Scientific Session of the American-College-of-Cardiology CY MAR 07-10, 2004 CL New Orleans, LA SP Amer Coll Cardiol C1 NIH, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 1 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 3 PY 2004 VL 43 IS 5 SU A BP 268A EP 268A DI 10.1016/S0735-1097(04)91139-4 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 780NW UT WOS:000189388501141 ER PT J AU Ingkanisorn, WP Hirsch, GA Dyke, CK Aletras, AH Kellman, P Arai, AE AF Ingkanisorn, WP Hirsch, GA Dyke, CK Aletras, AH Kellman, P Arai, AE TI Aortic gadolinium enhancement is associated with myocardial infarction, aging, and decreased aortic distensibility SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 54th Annual Scientific Session of the American-College-of-Cardiology CY MAR 07-10, 2004 CL New Orleans, LA SP Amer Coll Cardiol C1 NHLBI, 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 3 PY 2004 VL 43 IS 5 SU A BP 321A EP 321A DI 10.1016/S0735-1097(04)91359-9 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 780NW UT WOS:000189388501361 ER PT J AU Hashimoto, I Barber, BJ Jones, M Li, XK Sahn, DJ AF Hashimoto, I Barber, BJ Jones, M Li, XK Sahn, DJ TI Regional spectrum of tissue Doppler-derived myocardial acceleration during isovolumic relaxation and its relationship to peak filling SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 54th Annual Scientific Session of the American-College-of-Cardiology CY MAR 07-10, 2004 CL New Orleans, LA SP Amer Coll Cardiol C1 Oregon Hlth & Sci Univ, Portland, OR USA. NHLBI, 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 3 PY 2004 VL 43 IS 5 SU A BP 342A EP 342A DI 10.1016/S0735-1097(04)91449-0 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 780NW UT WOS:000189388501451 ER PT J AU Owens, DS Dyke, CK Arai, AE Plehn, JF AF Owens, DS Dyke, CK Arai, AE Plehn, JF TI Two-dimensional point-to-point measurements and best slice algorithm improve accuracy of echocardiographic left ventricular mass determination: A magnetic resonance imaging correlation in humans SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 54th Annual Scientific Session of the American-College-of-Cardiology CY MAR 07-10, 2004 CL New Orleans, LA SP Amer Coll Cardiol C1 NHLBI, 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 3 PY 2004 VL 43 IS 5 SU A BP 342A EP 342A DI 10.1016/S0735-1097(04)91447-7 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 780NW UT WOS:000189388501449 ER PT J AU Rhoads, KL Hsu, LY Ingkanisorn, WP Dyke, CK Syed, MA Kansal, P Aletras, AH Arai, AE AF Rhoads, KL Hsu, LY Ingkanisorn, WP Dyke, CK Syed, MA Kansal, P Aletras, AH Arai, AE TI The limits of quantifiable differences in dipyridamole stress magnetic resonance imaging perfusion defects in human subjects with coronary artery disease SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 54th Annual Scientific Session of the American-College-of-Cardiology CY MAR 07-10, 2004 CL New Orleans, LA SP Amer Coll Cardiol C1 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 3 PY 2004 VL 43 IS 5 SU A BP 353A EP 354A DI 10.1016/S0735-1097(04)91495-7 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 780NW UT WOS:000189388501497 ER PT J AU Shizukuda, Y Sachdev, V Ernst, I Nichols, JS Jison, M Brown, B Blackwelder, W Rodgers, GP Castro, O Ognibene, FP Plehn, JP Gladwin, MT AF Shizukuda, Y Sachdev, V Ernst, I Nichols, JS Jison, M Brown, B Blackwelder, W Rodgers, GP Castro, O Ognibene, FP Plehn, JP Gladwin, MT TI Pulmonary hypertension is strongly associated with mortality in sickle cell disease: Comparison of echocardiographic outcome predictors SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 54th Annual Scientific Session of the American-College-of-Cardiology CY MAR 07-10, 2004 CL New Orleans, LA SP Amer Coll Cardiol C1 NHLBI, Bethesda, MD 20892 USA. Howard Univ, Washington, DC 20059 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 3 PY 2004 VL 43 IS 5 SU A BP 421A EP 422A DI 10.1016/S0735-1097(04)91779-2 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 780NW UT WOS:000189388501782 ER PT J AU Powell, TM Paul, JD Hill, JM Read, EJ McCoy, PJ Cannon, RO AF Powell, TM Paul, JD Hill, JM Read, EJ McCoy, PJ Cannon, RO TI Granulocyte-colony stimulating factor mobilizes and activates endothelial progenitor cells in patients with coronary artery disease SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 54th Annual Scientific Session of the American-College-of-Cardiology CY MAR 07-10, 2004 CL New Orleans, LA SP Amer Coll Cardiol C1 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 3 PY 2004 VL 43 IS 5 SU A BP 458A EP 458A DI 10.1016/S0735-1097(04)91935-3 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 780NW UT WOS:000189388501938 ER PT J AU Halcox, J Zalos, G Charakida, M Quyyumi, AA AF Halcox, J Zalos, G Charakida, M Quyyumi, AA TI Obesity predicts coronary endothelial dysfunction independently of inflammation, atherosclerosis, and conventional risk factors SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 54th Annual Scientific Session of the American-College-of-Cardiology CY MAR 07-10, 2004 CL New Orleans, LA SP Amer Coll Cardiol C1 NIH, Bethesda, MD 20892 USA. Inst Child Hlth, London, England. NR 0 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 3 PY 2004 VL 43 IS 5 SU A BP 485A EP 485A DI 10.1016/S0735-1097(04)92050-5 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 780NW UT WOS:000189388502053 ER PT J AU Campia, U Sullivan, G Bryant, MB Cardillo, C Quon, MJ Panza, JA AF Campia, U Sullivan, G Bryant, MB Cardillo, C Quon, MJ Panza, JA TI Vascular endothelin-1 activity correlates with low-density lipoprotein cholesterol levels, but not with insulin sensitivity in hypercholesterolemic patients SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 54th Annual Scientific Session of the American-College-of-Cardiology CY MAR 07-10, 2004 CL New Orleans, LA SP Amer Coll Cardiol C1 NIH, Bethesda, MD 20892 USA. RI Quon, Michael/B-1970-2008 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 3 PY 2004 VL 43 IS 5 SU A BP 490A EP 490A DI 10.1016/S0735-1097(04)92073-6 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 780NW UT WOS:000189388502076 ER PT J AU Chuang, ML Salton, CJ Kissinger, KV O'Donnell, CJ Levy, D Manning, WJ AF Chuang, ML Salton, CJ Kissinger, KV O'Donnell, CJ Levy, D Manning, WJ TI Does indexation to fat-free mass eliminate or reverse gender differences in left ventricular mass? SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 54th Annual Scientific Session of the American-College-of-Cardiology CY MAR 07-10, 2004 CL New Orleans, LA SP Amer Coll Cardiol C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NHLBI, Framingham Heart Study, Framingham, MA 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 3 PY 2004 VL 43 IS 5 SU A BP 512A EP 512A DI 10.1016/S0735-1097(04)92170-5 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 780NW UT WOS:000189388502173 ER PT J AU Levy, D Kannel, WB AF Levy, D Kannel, WB TI Editorial comment - Postoperative atrial fibrillation and mortality: Do the risks merit changes in clinical practice? SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material ID HEART-FAILURE; MANAGEMENT; POPULATION C1 NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. Boston Univ, Sch Med, Div Cardiol, Boston, MA 02118 USA. Boston Univ, Sch Med, Div Prevent Med, Boston, MA 02118 USA. NHLBI, Bethesda, MD 20892 USA. RP Levy, D (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave, Framingham, MA 01702 USA. EM Dan@fram.nhlbi.nih.gov FU NHLBI NIH HHS [N01-HC-25195] NR 17 TC 21 Z9 23 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 3 PY 2004 VL 43 IS 5 BP 749 EP 751 DI 10.1016/j.jacc.2003.12.011 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 779AP UT WOS:000189273700006 PM 14998611 ER PT J AU Mosca, L Appel, LJ Benjamin, EJ Berra, K Chandra-Strobos, N Fabunmi, RP Grady, D Haan, CK Hayes, SN Judelson, DR Keenan, NL McBride, P Oparil, S Ouyang, P Oz, MC Mendelsohn, ME Pasternak, RC Pinn, VW Robertson, RM Schenck-Gustafsson, K Sila, CA Smith, SC Sopko, G Taylor, AL Walsh, BW Wenger, NK Williams, CL AF Mosca, L Appel, LJ Benjamin, EJ Berra, K Chandra-Strobos, N Fabunmi, RP Grady, D Haan, CK Hayes, SN Judelson, DR Keenan, NL McBride, P Oparil, S Ouyang, P Oz, MC Mendelsohn, ME Pasternak, RC Pinn, VW Robertson, RM Schenck-Gustafsson, K Sila, CA Smith, SC Sopko, G Taylor, AL Walsh, BW Wenger, NK Williams, CL CA Expert Panel Writing Grp TI Evidence-based guidelines for cardiovascular disease prevention in women SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Review DE AHA Scientific Statements; prevention; women; cardiovascular diseases; risk factors ID CORONARY-HEART-DISEASE; ACUTE MYOCARDIAL-INFARCTION; RANDOMIZED CONTROLLED-TRIAL; HORMONE REPLACEMENT THERAPY; HIGH-RISK PATIENTS; NONRHEUMATIC ATRIAL-FIBRILLATION; CONVERTING-ENZYME-INHIBITOR; PLACEBO-CONTROLLED TRIAL; DENSITY-LIPOPROTEIN CHOLESTEROL; FACTOR INTERVENTION TRIAL C1 Amer Heart Assoc, Dallas, TX 75231 USA. Amer Coll Cardiol, Bethesda, MD 20814 USA. Amer Coll Obstetricians & Gynecologists, Washington, DC 20090 USA. Amer Med Womens Assoc, Alexandria, VA 22314 USA. Assoc Black Cardiologists, Atlanta, GA 30303 USA. Ctr Dis Control & Prevent, Atlanta, GA USA. NHLBI, Bethesda, MD 20892 USA. Soc Thorac Surg, Chicago, IL 60611 USA. RP Amer Heart Assoc, Dallas, TX 75231 USA. OI Hayes, Sharonne/0000-0003-3129-362X; Benjamin, Emelia/0000-0003-4076-2336 NR 509 TC 52 Z9 53 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD MAR 3 PY 2004 VL 43 IS 5 BP 900 EP 921 DI 10.1016/j.jacc.2004.02.001 PG 22 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 779AP UT WOS:000189273700030 PM 14998635 ER PT J AU Kaye, FJ Harbour, JW AF Kaye, FJ Harbour, JW TI For whom the bell tolls: Susceptibility to common adult cancers in retinoblastoma survivors SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID ISOLATED UNILATERAL RETINOBLASTOMA; 2ND NONOCULAR TUMORS; LUNG-CANCER; MUTATIONS; NEOPLASMS; GENE; RISK; RB C1 Natl Naval Med Res Inst, Bethesda, MD 20889 USA. NCI, Genet Branch, Ctr Canc Res, Bethesda, MD 20892 USA. Washington Univ, Sch Med, Dept Ophthalmol & Visual Sci, Ocular Oncol Serv, St Louis, MO 63110 USA. RP Kaye, FJ (reprint author), Natl Naval Med Res Inst, Bldg 8,Rm 5101,8901 Wisconsin Ave, Bethesda, MD 20889 USA. EM fkaye@helix.nih.gov RI kaye, frederic/E-2437-2011 NR 17 TC 19 Z9 20 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD MAR 3 PY 2004 VL 96 IS 5 BP 342 EP 343 DI 10.1093/jnci/djh080 PG 2 WC Oncology SC Oncology GA 801IV UT WOS:000220090500001 PM 14996847 ER PT J AU Ganz, PA Kwan, L Stanton, AL Krupnick, JL Rowland, JH Meyerowitz, BE Bower, JE Belin, TR AF Ganz, PA Kwan, L Stanton, AL Krupnick, JL Rowland, JH Meyerowitz, BE Bower, JE Belin, TR TI Quality of life at the end of primary treatment of breast cancer: First results from the moving beyond cancer randomized trial SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID RECEIVING ADJUVANT CHEMOTHERAPY; COGNITIVE FUNCTION; PSYCHOLOGICAL DISTRESS; DYADIC ADJUSTMENT; COMMUNITY SAMPLE; LONG-TERM; WOMEN; SURVIVORS; THERAPY; IMPACT AB Background: During the last decade, survival rates for breast cancer have increased as a result of earlier detection and increased use of adjuvant therapy. Limited data exist on the psychosocial aspects of the transitional period between the end of primary treatment and survivorship. We investigated the baseline psychosocial status of women enrolled in a randomized trial testing two psychosocial interventions for women at the end of primary treatment. Methods: Participants, identified within I month after surgery (registration), provided demographic information and limited measures of quality of life. They were followed until they finished primary treatment (enrollment), at which time they completed a mailed baseline survey that included standardized measures of quality of life (including standardized scales of physical and emotional functioning), mood, symptoms, and sexual functioning. A total of 558 patients (mean age = 56.9 years) were enrolled in the study between July 1, 1999, and June 30, 2002. Health outcomes were examined according to treatment received: mastectomy with and without chemotherapy, and lumpectomy with and without chemotherapy. All statistical tests were two-sided. Results: Among all treatment groups, patients who had a mastectomy had the poorest physical functioning at registration (P<.001) and at enrollment (P = .05). At enrollment, mood and emotional functioning were similar among all patients, with no differences by type of treatment received. At enrollment, symptoms, including muscle stiffness, breast sensitivity, aches and pains, tendency to take naps, and difficulty concentrating, were common among patients in all groups and were statistically significantly associated with poor physical functioning and emotional well-being. Sexual functioning was worse for women who received chemotherapy than for those who did not, regardless of type of surgery (P<.001). Conclusions: At the end of primary treatment for breast cancer, women in all treatment groups report good emotional functioning but report decreased physical functioning, particularly among women who have a mastectomy or receive chemotherapy. Clinical interventions to address common symptoms associated with treatment should be considered to improve physical and emotional functioning at the end of primary treatment for breast cancer. C1 Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Div Canc Prevent & Control Res, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Inst Neuropsychiat, Cousins Ctr Psychoneuroimmunol, Los Angeles, CA 90095 USA. Georgetown Univ, Med Ctr, Dept Psychiat, Washington, DC 20007 USA. NCI, Off Canc Survivorship, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Univ So Calif, Dept Sociol, Los Angeles, CA 90089 USA. RP Ganz, PA (reprint author), Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Div Canc Prevent & Control Res, A2-125 CHS,Box 956900, Los Angeles, CA 90095 USA. EM pganz@ucla.edu FU NCI NIH HHS [R01-CA63028] NR 59 TC 266 Z9 278 U1 3 U2 39 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD MAR 3 PY 2004 VL 96 IS 5 BP 376 EP 387 DI 10.1093/jnci/djh060 PG 12 WC Oncology SC Oncology GA 801IV UT WOS:000220090500010 PM 14996859 ER PT J AU Woodson, K Flood, A Green, L Tangrea, JA Hanson, J Cash, B Schatzkin, A Schoenfeld, P AF Woodson, K Flood, A Green, L Tangrea, JA Hanson, J Cash, B Schatzkin, A Schoenfeld, P TI Loss of insulin-like growth factor-II imprinting and the presence of screen-detected colorectal adenomas in women SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID FREQUENT LOSS; CANCER; IGF2; GENE; HETEROZYGOSITY; EXPRESSION; OCCURS AB Loss of imprinting (LOI) of insulin-like growth factor-II (IGF-II) may be an inherited epigenetic trait that is polymorphic in the population, and its presence may predispose an individual to the development of colorectal cancer. We evaluated the association between LOI of IGF-II in normal colonic mucosal samples and adenomas in women participating in a colonoscopy screening study. Among 40 participants, 11 (27.5%) had LOI of IGF-II in their normal colonic mucosal tissue. After adjusting for body mass index and family history of colorectal cancer, LOI status was associated with a fivefold increased risk of adenoma formation (odds ratio = 5.2, 95% confidence interval = 1.0 to 26.7). On average, IGF-II expression was more than threefold higher among women with LOI of IGF-II than among women with normal imprinting status. Our findings support the hypothesis that LOI of IGF-II is an epigenetic trait polymorphic in the population and suggest that LOI of IGF-II may play a role in colorectal cancer. These findings are intriguing and need to be confirmed in larger studies. C1 NCI, Canc Prevent Studies Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. Univ Minnesota, Div Epidemiol, Minneapolis, MN 55455 USA. Natl Naval Med Res Inst, Bethesda, MD USA. Vet Affairs Med Ctr, Ctr Excellence Hlth Outcomes Res, Ann Arbor, MI USA. Univ Michigan, Sch Med, Div Gastroenterol, Ann Arbor, MI USA. RP Woodson, K (reprint author), NCI, Canc Prevent Studies Branch, Canc Res Ctr, NIH, 6116 Execut Blvd,Suite 705,MSC 8314, Bethesda, MD 20892 USA. EM kw114v@nih.gov FU NIDDK NIH HHS [K23DK060040] NR 14 TC 59 Z9 62 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD MAR 3 PY 2004 VL 96 IS 5 BP 407 EP 410 DI 10.1093/jnci/djh042 PG 4 WC Oncology SC Oncology GA 801IV UT WOS:000220090500014 PM 14996863 ER PT J AU Lowy, DR Nardelli-Haefliger, D Hildesheim, A Schiller, JT AF Lowy, DR Nardelli-Haefliger, D Hildesheim, A Schiller, JT TI Re: Specific antibody levels at the cervix during the menstrual cycle of women vaccinated with human papillomavirus 16 virus-like particles - Response SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter C1 NCI, Cellular Oncol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. CHU Vaudois, Dept Gynecol, CH-1011 Lausanne, Switzerland. RP Lowy, DR (reprint author), NCI, Cellular Oncol Lab, Ctr Canc Res, NIH, Bldg 37,Rm 4106, Bethesda, MD 20892 USA. EM drl@helix.nih.gov NR 3 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD MAR 3 PY 2004 VL 96 IS 5 BP 413 EP 414 DI 10.1093/jnci.djh072 PG 2 WC Oncology SC Oncology GA 801IV UT WOS:000220090500018 ER PT J AU Thompson, BL Erickson, K Schulkin, J Rosen, JB AF Thompson, BL Erickson, K Schulkin, J Rosen, JB TI Corticosterone facilitates retention of contextually conditioned fear and increases CRH mRNA expression in the amygdala SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE corticosterone; fear conditioning; memory; amygdala; CRH ID CORTICOTROPIN-RELEASING HORMONE; ACOUSTIC STARTLE REFLEX; PARAVENTRICULAR NUCLEUS; BASOLATERAL AMYGDALA; LONG-TERM; MEMORY CONSOLIDATION; STRIA TERMINALIS; ALLOSTATIC LOAD; GENE-EXPRESSION; RHESUS-MONKEYS AB The present study examined the effects of glucocorticoid administration on emotional memory and on corticotropin-releasing hormone (CRH) mRNA expression in the central nucleus of the amygdala (CeA) and the paraventricular nucleus of the hypothalamus (PVN). This was tested by administering repeated corticosterone (CORT) within a contextual fear conditioning paradigm. Rats received 2.5 mg/kg (s.c.) CORT or placebo twice a day for five and a half days and, 2h after the last injection, rats were given one-trial contextual fear conditioning. When tested for retention of conditioned fear 6 days later, the CORT-treated rats displayed more fear-conditioned freezing in the retention test than vehicle-treated rats, which was not accounted for by an increase in footshock responsivity nor elevated plasma CORT. Another group of rats was fear conditioned prior to CORT administration, followed 24 h later by the five and a half days of CORT, and tested 6 days later; conditioned fear was not enhanced in these rats. Finally, CORT administration produced an increase of CRH mRNA in the CeA and a decrease in the PVN. The data suggest that repeated administration of CORT given before fear conditioning facilitates the acquisition of emotional memory, whereas CORT given after consolidation does not increase emotional memory. (C) 2003 Elsevier B.V. All rights reserved. C1 Univ Delaware, Dept Psychol, Newark, DE 19716 USA. Univ Delaware, Neurosci Program, Newark, DE 19716 USA. NIMH, Mood & Anxiety Disorders Program, NIH, DHHS, Bethesda, MD 20814 USA. Georgetown Univ, Sch Med, Dept Physiol & Biophys, Washington, DC 20007 USA. NIMH, Clin Neuroendocrinol Branch, DHHS, Bethesda, MD 20892 USA. RP Rosen, JB (reprint author), Univ Delaware, Dept Psychol, 108 Wolf Hall, Newark, DE 19716 USA. EM jrosen@udel.edu FU NIDA NIH HHS [1 R03 DA12607-01] NR 48 TC 66 Z9 69 U1 2 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-4328 J9 BEHAV BRAIN RES JI Behav. Brain Res. PD MAR 2 PY 2004 VL 149 IS 2 BP 209 EP 215 DI 10.1016/S0166-4328(03)00216-X PG 7 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 775UU UT WOS:000189079700009 PM 15129783 ER PT J AU Sauna, ZE Andrus, MB Turner, TM Ambudkar, SV AF Sauna, ZE Andrus, MB Turner, TM Ambudkar, SV TI Biochemical basis of polyvalency as a strategy for enhancing the efficacy of P-glycoprotein (ABCB1) modulators: Stipiamide homodimers separated with defined-length spacers reverse drug efflux with greater efficacy SO BIOCHEMISTRY LA English DT Article ID MULTIDRUG-RESISTANCE REVERSAL; INDEXED COMBINATORIAL LIBRARY; ATP HYDROLYSIS; CATALYTIC CYCLE; FUNCTIONAL-CHARACTERIZATION; CYTOPLASMIC LEAFLET; NONNATURAL POLYENES; EXPRESSION SYSTEM; PLASMA-MEMBRANE; BINDING SITE AB Human P-glycoprotein (Pgp) is as an ATP-dependent efflux pump for a variety of chemotherapeutic drugs. The aim of this study is to evaluate whether Pgp modulators can be engineered to exhibit high-affinity binding using polyvalency. Five bivalent homodimeric polyenes based on stipiamide linked with polyethylene glycol ethers in the range of 3-50 Angstrom were synthesized and quantitatively characterized for their effect on Pgp function. The stipiamide homodimers displaced [I-125]iodoarylazidoprazoin (IAAP), an analogue of the Pgp substrate prazosin. A minimal spacer of 11 Angstrom is necessary for inhibition of IAAP labeling, beyond which there is an inverse correlation between the length of the spacer and the IC50 for the displacement of IAAP. ATP hydrolysis by Pgp on the other hand is stimulated by the dimers with spacers of up to 22 Angstrom, whereas dimers with longer spacers inhibit ATP hydrolysis. Finally, the homodimers reverse Pgp-mediated drug efflux in intact cells overexpressing Pgp, and 11 Angstrom is a threshold beyond which the effectiveness of the homodimers increases exponentially and levels off at 33 Angstrom. We demonstrate that dimerization and identification of an optimal spacer length increase by 11-fold the affinity of stipiamide, and this is reflected in the efficacy with which Pgp-mediated drug efflux is reversed. These results suggest that polyvalency could be a useful strategy for the development of more potent Pgp modulators. C1 NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Brigham Young Univ, Dept Chem & Biochem, Provo, UT 84602 USA. RP Ambudkar, SV (reprint author), NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bldg 37,Room 1B-22,37 Convent Dr, Bethesda, MD 20892 USA. EM ambudkar@helix.nih.gov RI Ambudkar, Suresh/B-5964-2008 NR 59 TC 45 Z9 46 U1 1 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAR 2 PY 2004 VL 43 IS 8 BP 2262 EP 2271 DI 10.1021/bi035965k PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 777PA UT WOS:000189185700013 PM 14979722 ER PT J AU Huang, CC Venturi, M Majeed, S Moore, MJ Phogat, S Zhang, MY Dimitrov, DS Hendrickson, WA Robinson, J Sodroski, J Wyatt, R Choe, H Farzan, M Kwong, PD AF Huang, CC Venturi, M Majeed, S Moore, MJ Phogat, S Zhang, MY Dimitrov, DS Hendrickson, WA Robinson, J Sodroski, J Wyatt, R Choe, H Farzan, M Kwong, PD TI Structural basis of tyrosine sulfation and V-H-gene usage in antibodies that recognize the HIV type 1 coreceptor-binding site on gp120 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; ENVELOPE GLYCOPROTEIN; NEUTRALIZING ANTIBODIES; CHEMOKINE RECEPTORS; CCR5; EPITOPES; ENTRY; RETROVIRUS; AIDS; SPECIFICITY AB The conserved surface of the HIV-1 gp120 envelope glycoprotein that binds to the HIV-1 coreceptor is protected from humoral recognition by multiple layers of camouflage. Here we present sequence and genomic analyses for 12 antibodies that pierce these defenses and determine the crystal structures of 5. The data reveal mechanisms and atomic-level details for three unusual immune features: posttranslational mimicry of coreceptor by tyrosine sulfation of antibody, an alternative molecular mechanism controlling such sulfation, and highly selective V-H-gene usage. When confronted by extraordinary viral defenses, the immune system unveils novel adaptive capabilities, with tyrosine sulfation enhancing the vocabulary of antigen recognition. C1 NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. Columbia Univ, Dept Biochem & Mol Biophys, New York, NY 10032 USA. Columbia Univ, Howard Hughes Med Inst, New York, NY 10032 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Sch Med, Dept Pediat,Dept Med Microbiol & Mol Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Div Aids, Boston, MA 02115 USA. NCI, NIH, Frederick, MD 21702 USA. Tulane Univ, Med Ctr, Dept Pediat, New Orleans, LA 70112 USA. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Kwong, PD (reprint author), NIAID, Vaccine Res Ctr, NIH, 40 Convent Dr,Bldg 40,Room 4508, Bethesda, MD 20892 USA. EM pdkwong@nih.gov FU NIAID NIH HHS [R01 AI043891] NR 39 TC 166 Z9 173 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 2 PY 2004 VL 101 IS 9 BP 2706 EP 2711 DI 10.1073/pnas.0308527100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 800ZD UT WOS:000220065300014 PM 14981267 ER PT J AU Padilla, PI Pacheco-Rodriguez, G Moss, J Vaughan, M AF Padilla, PI Pacheco-Rodriguez, G Moss, J Vaughan, M TI Nuclear localization and molecular partners of BIG1, a brefeldin A-inhibited guanine nucleotide-exchange protein for ADP-ribosylation factors SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SEC7 DOMAIN; EXPRESSION; CLONING; ARF; IDENTIFICATION; PURIFICATION; ARCHITECTURE; COMPLEX; MATRIX; CELLS AB Brefeldin A-inhibited guanine nucleotide-exchange protein 1 (BIG1) is an approximate to200-kDa brefeldin A-inhibited guanine nucleotide-exchange protein that preferentially activates ADP-ribosylation factor 1 (ARF1) and ARF3. BIG1 was found in cytosol in a multiprotein complex with a similar ARF-activating protein, BIG2, which is also an A kinase-anchoring protein. In HepG2 cells growing with serum, BIG1 was primarily cytosolic and Golgi-associated. After incubation overnight without serum, a large fraction of endogenous BIG1 was in the nuclei. By confocal immunofluorescence microscopy, BIG1 was localized with nucleoporin p62 at the nuclear envelope (probably during nucleocytoplasmic transport) and also in nucleoli, clearly visible against the less concentrated overall matrix staining. BIG1 was also identified by Western blot analyses in purified subnuclear fractions (e.g., nucleoli and nuclear matrix). Antibodies against BIG1, nucleoporin, or nucleolin coimmunoprecipitated the other two proteins from purified nuclei. In contrast, BIG2 was not associated with nuclear BIG1. Also of note, ARF was never detected among proteins precipitated from purified nuclei by anti-BIG1 antibodies, although microscopically the two proteins do appear sometimes to be colocalized in the nucleus. These data are consistent with independent intracellular movements and actions of BIG1 and BIG2, and they are also evidence of the participation of BIG1 in both Golgi and nuclear functions. C1 NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. RP Padilla, PI (reprint author), NHLBI, Pulm Crit Care Med Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. EM padillap@nhlbi.nih.gov NR 30 TC 22 Z9 24 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 2 PY 2004 VL 101 IS 9 BP 2752 EP 2757 DI 10.1073/pnas.0307345101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 800ZD UT WOS:000220065300022 PM 14973189 ER PT J AU Elbi, C Walker, DA Romero, G Sullivan, WP Toft, DO Hager, GL DeFranco, DB AF Elbi, C Walker, DA Romero, G Sullivan, WP Toft, DO Hager, GL DeFranco, DB TI Molecular chaperones function as steroid receptor nuclear mobility factors SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID GREEN FLUORESCENT PROTEIN; LIVING CELLS; GLUCOCORTICOID-RECEPTOR; SUBNUCLEAR TRAFFICKING; PROGESTERONE-RECEPTOR; HORMONE-RECEPTORS; HSP90; COMPLEXES; BINDING; HEAT-SHOCK-PROTEIN-90 AB Live cell imaging has revealed the rapid mobility of steroid hormone receptors within nuclei and their dynamic exchange at transcriptionally active target sites. Although a number of other proteins have been shown to be highly mobile within nuclei, the identity of soluble factors responsible for orchestrating nuclear trafficking remains unknown. We have developed a previously undescribed in situ subnuclear trafficking assay that generates transcriptionally active nuclei, which are depleted of soluble factors required for the nuclear mobility of glucocorticoid (GR) and progesterone receptors (PR). Using this system and a fluorescence recovery after photobleaching technique, we demonstrate that nuclear mobility of GR recovered on incubation with reticulocyte lysate was inhibited by geldanamycin, a drug that blocks the chaperone activity of heat-shock protein 90. Direct proof of molecular chaperone involvement in steroid receptor subnuclear trafficking was provided by the ATIP-dependent recovery of nuclear mobility of GR and PR on incubation with various combinations of purified chaperone and/or cochaperone proteins. Additionally, for both receptors, the inclusion of hormone during the recovery period leads to a retardation of nuclear mobility. Thus, our results provide a description of soluble nuclear mobility factors and furthermore demonstrate a previously unrecognized role for molecular chaperones in the regulation of steroid receptor function within the nucleus. C1 NCI, Lab Receptor Biol & Gene Express, Bethesda, MD 20892 USA. Univ Pittsburgh, Sch Med, Dept Pharmacol, Pittsburgh, PA 15261 USA. Mayo Grad Sch, Dept Biochem & Mol Biol, Rochester, MN 55905 USA. RP Hager, GL (reprint author), NCI, Lab Receptor Biol & Gene Express, Bldg 41,Room B602, Bethesda, MD 20892 USA. EM hagerg@exchange.nih.gov; dod1@pitt.edu NR 44 TC 105 Z9 110 U1 1 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 2 PY 2004 VL 101 IS 9 BP 2876 EP 2881 DI 10.1073/pnas.0400116101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 800ZD UT WOS:000220065300043 PM 14978266 ER PT J AU de Silanes, IL Zhan, M Lal, A Yang, XL Gorospe, M AF de Silanes, IL Zhan, M Lal, A Yang, XL Gorospe, M TI Identification of a target RNA motif for RNA-binding protein HuR SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE mRNA stability; posttranscriptional; gene expression; ribonucleoprotein; complex; cDNA array ID FACTOR MESSENGER-RNAS; GENE-EXPRESSION; RICH ELEMENT; 3'-UNTRANSLATED REGION; UNTRANSLATED REGION; CDNA ARRAYS; TRANSLATION; STABILITY; HEL-N1; DIFFERENTIATION AB HuR, a protein that binds to specific mRNA subsets, is increasingly recognized as a pivotal posttranscriptional regulator of gene expression. Here, HuR was immunoprecipitated under conditions that preserved HuR-RNA interactions, and HuR-bound target mRNAs were identified by cDNA array hybridization. Analysis of primary sequences and secondary structures shared among HuR targets led to the identification of a 17- to 20-base-long RNA motif rich in uracils. This HuR motif was found in almost all mRNAs previously reported to be HuR targets, was located preferentially within 3' untranslated regions of all unigene transcripts examined, and was conserved in >50% of human and mouse homologous genes. Importantly, the HuR motif allowed the successful prediction and subsequent validation of novel HuR targets from gene databases. This study describes an HuR target RNA motif and presents a general strategy for identifying target motifs for IRNA-binding proteins. C1 NIA, Intramural Res Program, Res Resources Branch, NIH, Baltimore, MD 21224 USA. NIA, Intramural Res Program, Cellular & Mol Biol Lab, NIH, Baltimore, MD 21224 USA. RP Gorospe, M (reprint author), NIA, Intramural Res Program, Res Resources Branch, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM myriam-gorospe@nih.gov RI Lopez de Silanes, Isabel/K-4962-2015 OI Lopez de Silanes, Isabel/0000-0001-6762-9792 NR 46 TC 174 Z9 176 U1 2 U2 11 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 2 PY 2004 VL 101 IS 9 BP 2987 EP 2992 DI 10.1073/pnas.0306453101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 800ZD UT WOS:000220065300062 ER PT J AU Voutetakis, A Kok, MR Zheng, CY Bossis, I Wang, JH Cotrim, AP Marracino, N Goldsmith, CM Chiorini, JA Loh, YP Nieman, LK Baum, BJ AF Voutetakis, A Kok, MR Zheng, CY Bossis, I Wang, JH Cotrim, AP Marracino, N Goldsmith, CM Chiorini, JA Loh, YP Nieman, LK Baum, BJ TI Reengineered salivary glands are stable endogenous bioreactors for systemic gene therapeutics SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID RECOMBINANT ADENOASSOCIATED VIRUS; IN-VIVO; BETA-THALASSEMIA; VECTORS; DELIVERY; ERYTHROPOIETIN; MUSCLE; MICE; EXPRESSION; SECRETION AB The use of critical-for-life organs (e.g., liver or lung) for systemic gene therapeutics can lead to serious safety concerns. To circumvent such issues, we have considered salivary glands (SGs) as an alternative gene therapeutics target tissue. Given the high secretory abilities of SGs, we hypothesized that administration of low doses of recombinant adeno-associated virus (AAV) vectors would allow for therapeutic levels of transgene-encoded secretory proteins in the bloodstream. We administered 10(9) particles of an AAV vector encoding human erythropoietin (hEPO) directly to individual mouse submandibular SGs. Serum hEPO reached maximum levels 8-12 weeks after gene delivery and remained relatively stable for 54 weeks (longest time studied). Hematocrit levels were similarly increased. Moreover, these effects proved to be vector dose-dependent, and even a dosage as low as 10(8) particles per animal led to significant increases in hEPO and hematocrit levels. Vector DNA was detected only within the targeted SGs, and levels of AAV copies within SGs were highly correlated with serum hEPO levels (r = 0.98). These results show that SGs appear to be promising targets with potential clinical applicability for systemic gene therapeutics. C1 US Dept HHS, NICHHD, Pediat & Reprod endocrinol Branch, NIH, Bethesda, MD 20892 USA. US Dept HHS, Natl Inst Dent & Craniofacial Res, Gene Therapy & Therapeut Branch, NIH, Bethesda, MD 20892 USA. US Dept HHS, NICHHD, Dev Neurobiol Lab, Sect Cellular Neurobiol,NIH, Bethesda, MD 20892 USA. Acad Med Ctr, Dept Clin Immunol, NL-1100 DD Amsterdam, Netherlands. RP Baum, BJ (reprint author), US Dept HHS, NICHHD, Pediat & Reprod endocrinol Branch, NIH, Bethesda, MD 20892 USA. EM bbaum@dir.nidcr.nih.gov NR 39 TC 68 Z9 71 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 2 PY 2004 VL 101 IS 9 BP 3053 EP 3058 DI 10.1073/pnas.0400136101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 800ZD UT WOS:000220065300073 PM 14978265 ER PT J AU Bera, TK Das, S Maeda, H Beers, R Wolfgang, CD Kumar, V Hahn, Y Lee, BK Pastan, I AF Bera, TK Das, S Maeda, H Beers, R Wolfgang, CD Kumar, V Hahn, Y Lee, BK Pastan, I TI NGEP, a gene encoding a membrane protein detected only in prostate cancer and normal prostate SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID BREAST-CANCER; EXPRESSION; RECEPTOR; HOMOLOGY; DATABASE; ANTIGEN; TESTIS; CELLS AB We identified a gene (NGEP) that is expressed only in prostate cancer and normal prostate. The two NGEP transcripts are 0.9 kb and 3.5 kb in size and are generated by a differential splicing event. The short variant (NGEP-S) is derived from four exons and encodes a 20-kDa intracellular protein. The long form (NGEP-L) is derived from 18 exons and encodes a 95-kDa protein that is predicted to contain seven-membrane-spanning regions. In situ hybridization shows that NGEP mRNA is localized in epithelia[ cells of normal prostate and prostate cancers. Immunocytochemical analysis of cells transfected with NGEP cDNAs containing a Myc epitope tag at the carboxyl terminus shows that the protein encoded by the short transcript is localized in the cytoplasm, whereas the protein encoded by the long transcript is present on the plasma membrane. Because of its selective expression in prostate cancer and its presence on the cell surface, NGEP-L is a promising target for the antibody-based therapies of prostate cancer. C1 NCI, Mol Biol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Pastan, I (reprint author), NCI, Mol Biol Lab, Canc Res Ctr, NIH, 37 Convent Dr,Room 5106, Bethesda, MD 20892 USA. EM pastani@mail.nih.gov NR 21 TC 46 Z9 52 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 2 PY 2004 VL 101 IS 9 BP 3059 EP 3064 DI 10.1073/pnas.0308746101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 800ZD UT WOS:000220065300074 PM 14981236 ER PT J AU Kouprina, N Mullokandov, M Rogozin, IB Collins, NK Solomon, G Otstot, J Risinger, JI Koonin, EV Barrett, JC Larionov, V AF Kouprina, N Mullokandov, M Rogozin, IB Collins, NK Solomon, G Otstot, J Risinger, JI Koonin, EV Barrett, JC Larionov, V TI The SPANX gene family of cancer/testis-specific antigens: Rapid evolution and amplification in African great apes and hominids SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID SEGMENTAL DUPLICATIONS; REPRODUCTIVE PROTEINS; GENOMIC ORGANIZATION; HUMAN SPERMATOZOA; CELL-LINES; EXPRESSION; SELECTION; LOCALIZATION; SUBSTITUTION; ALIGNMENT AB Human sperm protein associated with the nucleus on the X chromosome (SPANX) genes comprise a gene family with five known members (SPANX-A1, -A2, -B, -C and -D), encoding cancer/testis-specific antigens that are potential targets for cancer immunotherapy. These highly similar paralogous genes cluster on the X chromosome at Xq27. We isolated and sequenced primate genomic clones homologous to human SPANX Analysis of these clones and search of the human genome sequence revealed an uncharacterized group of genes, SPANX-N, which are present in all primates as well as in mouse and rat. In humans, four SPANX-N genes comprise a series of tandem duplicates at Xq27; a fifth member of this subfamily is located at Xp11. Similarly to SPANX-A/D, human SPANX-N genes are expressed in normal testis and some melanoma cell lines; testis-specific expression of SPANX is also conserved in mouse. Analysis of the taxonomic distribution of the long and short forms of the intron indicates that SPANX-N is the ancestral form, from which the SPANX-A/D subfamily evolved in the common ancestor of the hominoid lineage. Strikingly, the coding sequences of the SPANX genes evolved much faster than the intron and the 5' untranslated region. There is a strong correlation between the rates of evolution of synonymous and nonsynonymous codon positions, both of which are accelerated 2-fold or more compared to the noncoding sequences. Thus, evolution of the SPANX family appears to have involved positive selection that affected not only the protein sequence but also the synonymous sites in the coding sequence. C1 NCI, Lab Biosyst & Canc, Bethesda, MD 20892 USA. Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA. NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. RP Larionov, V (reprint author), NCI, Lab Biosyst & Canc, Bethesda, MD 20892 USA. EM larionov@mail.nih.gov NR 34 TC 45 Z9 58 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 2 PY 2004 VL 101 IS 9 BP 3077 EP 3082 DI 10.1073/pnas.0308532100 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 800ZD UT WOS:000220065300077 PM 14973187 ER PT J AU Grimm, D Tilly, K Byram, R Stewart, PE Krum, JG Bueschel, DM Schwan, TG Policastro, PF Elias, AF Rosa, PA AF Grimm, D Tilly, K Byram, R Stewart, PE Krum, JG Bueschel, DM Schwan, TG Policastro, PF Elias, AF Rosa, PA TI Outer-surface protein C of the Lyme disease spirochete: A protein induced in ticks for infection of mammals SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID BORRELIA-BURGDORFERI; CRYSTAL-STRUCTURE; GENE-EXPRESSION; OSPC; ANTIGEN; IXODIDAE; ANTIBODY; FAMILY; ACARI; MICE AB Environmentally responsive synthesis of surface proteins represents a hallmark of the infectious cycle of the Lyme disease agent, Borrelia burgdorferi. Here we created and analyzed a B. burgdorferi mutant lacking outer-surface protein C (OspC), an abundant Osp that spirochetes normally synthesize in the tick vector during the blood meal and down-regulate after transmission to the mammal. We demonstrate that B. burgdorferi strictly requires OspC to infect mice but not to localize or migrate appropriately in the tick. The induction of a spirochetal virulence factor preceding the time and host in which it is required demonstrates a developmental sequence for transmission of this arthropod-borne pathogen. C1 NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIAID, Hamilton, MT 59840 USA. Univ Wyoming, Dept Mol Biol, Laramie, WY 82071 USA. RP Rosa, PA (reprint author), NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIAID, 903 S 4th St, Hamilton, MT 59840 USA. EM prosa@niaid.nih.gov NR 43 TC 271 Z9 278 U1 1 U2 10 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 2 PY 2004 VL 101 IS 9 BP 3142 EP 3147 DI 10.1073/pnas.0306845101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 800ZD UT WOS:000220065300088 PM 14970347 ER PT J AU Elefteriou, F Takeda, S Ebihara, K Magre, J Patano, N Kim, CA Ogawa, Y Liu, X Ware, SM Craigen, WJ Robert, JJ Vinson, C Nakao, K Capeau, J Karsenty, G AF Elefteriou, F Takeda, S Ebihara, K Magre, J Patano, N Kim, CA Ogawa, Y Liu, X Ware, SM Craigen, WJ Robert, JJ Vinson, C Nakao, K Capeau, J Karsenty, G TI Serum leptin level is a regulator of bone mass SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID POSTMENOPAUSAL WOMEN; LIFE-SPAN; MICE; RECEPTORS; DENSITY; OSTEOPOROSIS; EXPRESSION; METABOLISM; ELEGANS; PROTEIN AB Leptin is a powerful inhibitor of bone formation in vivo. This antiosteogenic function involves leptin binding to its receptors on ventromedial hypothalamic neurons, the autonomous nervous system and beta-adrenergic receptors on osteoblasts. However, the mechanisms whereby leptin controls the function of ventromedial hypothalamic antiosteogenic neurons remain unclear. In this study, we compared the ability of leptin to regulate body weight and bone mass and show that leptin antiosteogenic and anorexigenic functions are affected by similar amounts of leptin. Using a knock-in of LacZ in the leptin locus, we failed to detect any leptin synthesis in the central nervous system. However, increasing serum leptin level, even dramatically, reduced bone mass. Conversely, reducing serum-free leptin level by overexpressing a soluble receptor for leptin increased bone mass. Congruent with these results, the high bone mass of lipodystrophic mice could be corrected by restoring serum leptin level, suggesting that leptin is an adipocyte product both necessary and sufficient to control bone mass. Consistent with the high bone mass phenotype of lipodystrophic mice, we observed an advanced bone age, an indirect reflection of premature bone formation, in lipodystrophic patients. Taken together, these results indicate that adipocyte-derived circulating leptin is a determinant of bone formation and suggests that leptin antiosteogenic function is conserved in vertebrates. C1 Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. Baylor Coll Med, Bone Dis Program Texas, Houston, TX 77030 USA. Kyoto Univ, Grad Sch Med, Dept Med & Clin Sci, Kyoto 6068507, Japan. Univ Paris 06, INSERM U402, F-75012 Paris, France. Genet Inst Crianca, BR-05403900 Sao Paulo, Brazil. Tokyo Med & Dent Univ, Ctr Excellence Program Frontier Res Mol Destruct, Tokyo 1010062, Japan. Med Res Inst, Dept Mol Med & Metab, F-75730 Paris, France. Hop Necker Enfants Malad, Dept Pediat Diabetol, F-75730 Paris, France. NCI, Biochem Lab, Bethesda, MD 20892 USA. RP Karsenty, G (reprint author), Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. EM karsenty@bcm.tmc.edu RI takeda, shu/B-5195-2012; MAGRE, Jocelyne/D-4788-2015 FU NIDDK NIH HHS [DK 5883] NR 27 TC 200 Z9 216 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 2 PY 2004 VL 101 IS 9 BP 3258 EP 3263 DI 10.1073/pnas.0308744101 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 800ZD UT WOS:000220065300108 PM 14978271 ER PT J AU Pandit, SD Li, KCP AF Pandit, SD Li, KCP TI A primer on molecular biology for imagers: II. Transcription and gene expression SO ACADEMIC RADIOLOGY LA English DT Article C1 NIH, Mol Imaging Lab, Dept Diagnost Radiol, Ctr Clin, Bethesda, MD 20892 USA. RP Pandit, SD (reprint author), NIH, Mol Imaging Lab, Dept Diagnost Radiol, Ctr Clin, 10-1N306,9000 Rockville Pike, Bethesda, MD 20892 USA. EM spandit@mail.cc.nih.gov NR 12 TC 8 Z9 8 U1 0 U2 0 PU ASSOC UNIV RADIOLOGISTS PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523-2251 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD MAR PY 2004 VL 11 IS 3 BP 333 EP 344 DI 10.1016/S1076-6332(03)00716-5 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 779CF UT WOS:000189277500012 PM 15035524 ER PT J AU Deschamps, JR Coop, A Parrish, DA Rice, KC AF Deschamps, JR Coop, A Parrish, DA Rice, KC TI 7 beta, 14 beta-epoxyhydrocodone-6,6-dimethoxy ketal: an unusual oxetane-containing opioid SO ACTA CRYSTALLOGRAPHICA SECTION E-STRUCTURE REPORTS ONLINE LA English DT Article ID ANALGESIC NARCOTIC-ANTAGONISTS; CRYSTAL C1 USN, Res Lab, Struct Matter Lab, Washington, DC 20375 USA. NIDDKD, Med Chem Lab, NIH, Bethesda, MD 20892 USA. RP Deschamps, JR (reprint author), USN, Res Lab, Struct Matter Lab, Code 6030, Washington, DC 20375 USA. EM deschamps@nrl.navy.mil OI Deschamps, Jeffrey/0000-0001-5845-0010 NR 9 TC 0 Z9 0 U1 0 U2 2 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1600-5368 J9 ACTA CRYSTALLOGR E JI Acta Crystallogr. Sect. E.-Struct Rep. Online PD MAR PY 2004 VL 60 BP O331 EP O333 DI 10.1107/S1600536804002077 PN 3 PG 3 WC Crystallography SC Crystallography GA 778XC UT WOS:000189265800051 ER PT J AU Shpargel, KB Makishima, T Griffith, AJ AF Shpargel, KB Makishima, T Griffith, AJ TI Col11a1 and Col11a2 mRNA expression in the developing mouse cochlea: Implications for the correlation of hearing loss phenotype with mutant type XI collagen genotype SO ACTA OTO-LARYNGOLOGICA LA English DT Article DE basilar membrane; deafness; DFNA13; extracellular matrix; genetic; Marshall syndrome; Stickler syndrome; tectorial membrane ID TECTORIAL MEMBRANE; STICKLER-SYNDROME; MARSHALL-SYNDROME; II COLLAGEN; INNER-EAR; GENE; MUTATIONS; LOCUS; COL2A1 AB Objective - Mutations in the fibrillar collagen genes COL11A1 and COL11A2 can cause sensorineural hearing loss associated with Stickler syndrome. There is a correlation of hearing loss severity, onset, progression and affected frequencies with the underlying mutated collagen gene. We sought to determine whether differences in spatial or temporal expression of these genes underlie this correlation, and to identify the cochlear cell populations expressing these genes and the structures likely to be affected by mutations. Materials and Methods - We used in situ hybridization analysis of C57BL/6J mouse temporal bones. Results - Similar, diffuse expression of Col11a1 and Col11a2 mRNA was first observed in the cochlear duct at embryonic Day 15.5, with increasingly focal hybridization being noted at postnatal Days 1 and 5 in the greater epithelial ridge and lateral wall of the cochlea. The greater epithelial ridge appeared to be the main, if not only, source of mRNA encoding Col11a1 and Col11a2 in the tectorial membrane. At postnatal Day 13, Col11a1 and Col11a2 expression became more focal and co-localized in the inner sulcus, Claudius' cells and cells of Boettcher. Conclusions - We did not observe spatial or temporal differences in mRNA expression that could account for the auditory phenotype - genotype correlation. The expression patterns suggest essential roles for Col11a1 and Col11a2 in the basilar or tectorial membranes. C1 Natl Inst Deafness & Other Commun Disorders, NIH, Sect Gene Struct & Funct, Rockville, MD 20850 USA. Natl Inst Deafness & Other Commun Disorders, NIH, Hearing Sect, Rockville, MD 20850 USA. RP Griffith, AJ (reprint author), Natl Inst Deafness & Other Commun Disorders, NIH, Sect Gene Struct & Funct, 5 Res Court,Room 2A-01, Rockville, MD 20850 USA. EM griffita@nidcd.nih.gov FU NIDCD NIH HHS [Z01-DC00060-02] NR 25 TC 13 Z9 14 U1 1 U2 3 PU TAYLOR & FRANCIS AS PI OSLO PA CORT ADELERSGT 17, PO BOX 2562, SOLLI, 0202 OSLO, NORWAY SN 0001-6489 J9 ACTA OTO-LARYNGOL JI Acta Oto-Laryngol. PD MAR PY 2004 VL 124 IS 3 BP 242 EP 248 DI 10.1080/00016480410016162 PG 7 WC Otorhinolaryngology SC Otorhinolaryngology GA 810FS UT WOS:000220690800004 PM 15141750 ER PT J AU Bennett, GG Merritt, MM Edwards, CL Sollers, JJ AF Bennett, GG Merritt, MM Edwards, CL Sollers, JJ TI Perceived racism and affective responses to ambiguous interpersonal interactions among African American men SO AMERICAN BEHAVIORAL SCIENTIST LA English DT Article DE racism; discrimination; emotions; stress; ethnicity ID CARDIOVASCULAR REACTIVITY; DISCRIMINATION AB The current study examined affective responses to ambiguous interpersonal interactions containing both ambiguous and overtly racist content. Participants included 74 African American males (ages 18-47), half of whom heard a depiction of a negative social interaction with blatantly racist content (BRC). The remaining participants heard a similar scenario containing no racist content (NRC). Negative affect scores were higher for those in the BRC group, yet individuals in the ambiguous (NRC) condition who reported perceptions of racism in the scenario showed greater negative affect reactivity than those who saw no racism in the scenario. Among those in the NRC group, self-reported past experiences with racial discrimination moderated the effect of perceived racism on negative affect. The authors conclude that the perception of racial discrimination, in particular when evaluating ambiguous situations, may have profound affective consequences for Black men. C1 Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Boston, MA 02115 USA. NIA, Gerontol Res Ctr, Bethesda, MD 20892 USA. Duke Univ, Dept Med, Div Hematol, Durham, NC 27706 USA. Duke Univ, Dept Psychiat, Durham, NC 27706 USA. RP Bennett, GG (reprint author), Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 15 TC 27 Z9 27 U1 3 U2 6 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0002-7642 J9 AM BEHAV SCI JI Am. Behav. Sci. PD MAR PY 2004 VL 47 IS 7 BP 963 EP 976 DI 10.1177/0002764203261070 PG 14 WC Psychology, Clinical; Social Sciences, Interdisciplinary SC Psychology; Social Sciences - Other Topics GA 772QZ UT WOS:000188853900007 ER PT J AU Ellison, RC Zhang, YQ Qureshi, MM Knox, S Arnett, DK Province, MA AF Ellison, RC Zhang, YQ Qureshi, MM Knox, S Arnett, DK Province, MA CA Investigators NHLBI Family Heart TI Lifestyle determinants of high-density lipoprotein cholesterol: The National Heart, Lung, and Blood Institute Family Heart Study SO AMERICAN HEART JOURNAL LA English DT Article ID APOLIPOPROTEIN-A-I; ESTER TRANSFER PROTEIN; PLASMA TRIGLYCERIDE CLEARANCE; MODERATE ALCOHOL INTAKE; HEPATIC LIPASE; CIGARETTE-SMOKING; HDL CHOLESTEROL; PROLONGED EXERCISE; SEDENTARY MEN; CONSUMPTION AB Background While genetic factors are major determinants of high-density lipoprotein cholesterol (HIDL-C), environmental factors also play a role. The latter include 3 modifiable lifestyle factors: alcohol consumption, physical activity, and smoking. Methods We compared the relative effects of alcohol, physical activity, and smoking on HDL-C levels, using data from 2309 subjects (1226 women and 1083 men), aged 25 to 91 years, from randomly selected families, participating in the National Heart, Lung, and Blood Institute Family Heart Study. Results Alcohol consumption was associated with the largest increment in HDL-C (an increase of 9.0-13.1 mg/dL from nondrinker to highest categories); physical activity with a more modest increment (an increase of 3.0-3.3 mg/dL from lowest to highest categories); and cigarette smoking with a large decrement in women (a decrease of 9.9 mg/dL) and a modest one in men (a decrease of 2.6 mg/dL) between nonsmoker and greater than or equal to20 cigarettes per day categories. The 3 lifestyle behaviors plus age, body mass index, education, and current estrogen use explained 22.4% and 18.2% of the total variance of HDL-C for women and men, respectively. Alcohol accounted for 28.6% of this variance among women and 50.1% among men; smoking accounted for 6.7% and 3.3%, respectively, and physical activity for 2.7% and 3.6%, respectively, among women and men. Age, body mass index, education, and current estrogen use explained the remaining 62.0% and 43.0%, respectively, of the variance attributed to environmental factors. Conclusions This study suggests that, among lifestyle behaviors, alcohol consumption is the more important correlate of HDL-cholesterol. C1 Boston Univ, Sch Med, Evans Dept Med, Prevent Med & Epidemiol Sect, Boston, MA 02118 USA. Boston Univ, Sch Publ Hlth, Boston, MA USA. NHLBI, Div Epidemiol & Clin Applicat, Rockville, MD USA. Univ Minnesota, Sch Publ Hlth, Minneapolis, MN USA. Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA. RP Ellison, RC (reprint author), Boston Univ, Sch Med, Evans Dept Med, Prevent Med & Epidemiol Sect, Room B-612,715 Albany St, Boston, MA 02118 USA. EM ellison@bu.edu OI Ellison, Robert Curtis/0000-0002-0582-7467; Zhang, Yuqing/0000-0001-7954-1149 FU NHLBI NIH HHS [U01 HL56568, U01 HL56563, U01 HL56564, U01 HL56565, U01 HL56566, U01 HL56567, U01 HL56569] NR 55 TC 94 Z9 99 U1 1 U2 4 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD MAR PY 2004 VL 147 IS 3 BP 529 EP 535 DI 10.1016/j.ahj.2003.10.033 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 807ZM UT WOS:000220539400030 PM 14999205 ER PT J AU Salbe, AD DelParigi, A Pratley, RE Drewnowski, A Tataranni, PA AF Salbe, AD DelParigi, A Pratley, RE Drewnowski, A Tataranni, PA TI Taste preferences and body weight changes in an obesity-prone population SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE taste perceptions; hedonic responses; obesity; Pima Indians; palatability and weight gain; food intake ID X-RAY ABSORPTIOMETRY; PIMA-INDIANS; FOOD-INTAKE; ENERGY-INTAKE; FAT; DOPAMINE; SWEET; RESPONSIVENESS; DETERMINANTS; CONSUMERS AB Background: Taste preferences for highly palatable foods rich in sugar and fat may underlie the current epidemic of obesity. Objective: This study aimed to determine whether the hedonic response to sweet and creamy solutions differs between whites and Pima Indians and whether a preference for these tastes predicts weight gain. Design: One hundred twenty-three Pima Indian and 64 white volunteers taste tested solutions of nonfat milk (0.1% fat), whole milk (3.5% fat), half and half (11.3% fat), and cream (37.5% fat) containing 0%, 5%, 10%, or 20% sugar by weight. Solutions were rated for perceived sweetness, creaminess, and pleasantness (hedonic response) on a 100-mm visual analogue scale. Follow-up body weight was measured in 75 Pima Indians 5.5 +/- 3.0 y ((x) over bar +/- SD) after baseline taste testing. Results: The Pima Indians had a significantly (P = 0.006) lower hedonic response than did the whites (repeated-measures analysis of variance). Neither body size (P = 0.56) nor adiposity (P = 0.86) was a significant predictor of the hedonic response. There was a positive correlation (r = 0.28, P = 0.01) between the maximal hedonic response at baseline and subsequent weight gain in the Pima Indians. Conclusion: Although the Pima Indians liked sweet and creamy solutions less than the whites did, a heightened hedonic response for these solutions among the Pima Indians was associated with weight gain. C1 NIDDKD, Clin Diabet & Nutr Sect, Phoenix Epidemiol & CLin Res Branch, NIH, Phoenix, AZ 85016 USA. Univ Washington, Nutr Sci Program, Seattle, WA 98195 USA. RP Salbe, AD (reprint author), NIDDK, NIH, CDNS, 4212 N 16th St,Room 541, Phoenix, AZ 85016 USA. EM arline_salbe@nih.gov FU NCI NIH HHS [CA61680] NR 39 TC 74 Z9 77 U1 1 U2 10 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD MAR PY 2004 VL 79 IS 3 BP 372 EP 378 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 777RD UT WOS:000189190600005 PM 14985209 ER PT J AU Farmer, TW Price, LSN O'Neal, KK Leung, MC Goforth, JB Cairns, BD Reese, LRE AF Farmer, TW Price, LSN O'Neal, KK Leung, MC Goforth, JB Cairns, BD Reese, LRE TI Exploring risk in early adolescent African American youth SO AMERICAN JOURNAL OF COMMUNITY PSYCHOLOGY LA English DT Article DE adolescence; configurations; adjustment; African American ID CHILDREN; CONFIGURATIONS; AGGRESSION; VIOLENCE; IMPACT; BOYS AB Two studies were conducted to explore the degree to which single- and multiple-risk profiles were evident in samples of African American early adolescents in low-income inner-city, rural, and suburban schools. Study 1 examined early adolescent risk status (i.e., single, multiple) in relation to later adjustment in a representative sample (70% European American, 30% African American). Youthwhoexperienced a single risk in early adolescence had moderately increased levels of school dropout and criminal arrests, whereas youth with multiple risks (i.e., combination of 2 or more risks) had significantly increased levels of school dropout, criminal arrests, and teen parenthood. Study 2 examined the extent to which single- and multiple-risk profiles were evident in cross-sectional samples of African American youth from low-income inner-city and rural areas. About one fourth of both the inner-city and rural samples of African American youth were composed of youth in the single- risk category. A significantly greater proportion of boys in the inner-city sample (20%) than boys in the rural sample (13%) experienced multiple risks. Girls across the rural and inner-city samples did not differ in terms of risk. Overall, more than 60% of African American youth in these two low-income samples did not evidence risk for later adjustment problems. Implications for research and intervention are discussed. C1 Univ N Carolina, Ctr Dev Sci, Chapel Hill, NC 27599 USA. NIMH, Dev Psychopathol & Prevent Res Branch, Rockville, MD 20857 USA. Ctr Dis Control & Prevent, Natl Ctr Injury Prevent & Control, Atlanta, GA USA. RP Farmer, TW (reprint author), Univ N Carolina, Ctr Dev Sci, CB 8115, Chapel Hill, NC 27599 USA. EM tfarmer@email.unc.edu FU NIMH NIH HHS [MH52429]; ODCDC CDC HHS [R49CCR419824, U81CCU416369] NR 19 TC 22 Z9 23 U1 2 U2 4 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0091-0562 J9 AM J COMMUN PSYCHOL JI Am. J. Community Psychol. PD MAR PY 2004 VL 33 IS 1-2 BP 51 EP 59 DI 10.1023/B:AJCP.0000014318.16652.30 PG 9 WC Public, Environmental & Occupational Health; Psychology, Multidisciplinary; Social Work SC Public, Environmental & Occupational Health; Psychology; Social Work GA 770EH UT WOS:000188709900006 PM 15055754 ER PT J AU Platz, EA Leitzmann, MF Rimm, EB Willett, WC Giovannucci, E AF Platz, EA Leitzmann, MF Rimm, EB Willett, WC Giovannucci, E TI Alcohol intake, drinking patterns, and risk of prostate cancer in a large prospective cohort study SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE alcohol drinking; cohort studies; ethanol; prostatic neoplasms; risk ID LIFE-STYLE FACTORS; GROWTH-FACTOR-I; UNITED-STATES; RAT-LIVER; PHYSICAL-ACTIVITY; OXIDATIVE STRESS; DIETARY-FAT; CONSUMPTION; MEN; ETHANOL AB Alcohol drinking has been extensively studied in relation to prostate cancer, yet findings on the direction of the association are equivocal. Previous studies have not examined drinking patterns. Thus, the authors prospectively evaluated the associations between these factors and risk of incident prostate cancer (n = 2,479) in a cohort study of 47,843 US men (1986-1998). The men completed a questionnaire at baseline that included information on consumption of specific types of alcohol and frequency of use. The authors estimated hazard ratios using Cox proportional hazards regression for average alcohol intake and number of days per week on which alcohol was consumed stratified by average weekly intake (<105 g/week vs. greater than or equal to105 g/week). Compared with nondrinking, the hazard ratio for consumption increased slightly from an average of 5.0-14.9 g/day (hazard ratio (HR) = 1.05, 95% confidence interval (CI): 0.94, 1.18) to 30.0-49.9 g/day (HR = 1.13, 95% CI: 0.96, 1.33), but it was not increased at greater than or equal to50 g/day (HR = 1.00, 95% CI: 0.77, 1.31) after adjustment for recent smoking and other factors. Compared with abstainers, risk was greatest among men who consumed an average of greater than or equal to105 g/week but who drank on only 1-2 days per week (HR = 1.64, 95% CI: 1.13, 2.38). These results suggest that moderate or greater alcohol consumption is not a strong contributor to prostate cancer risk, except possibly in men who consume large amounts infrequently. C1 Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, James Buchanan Brady Urol Inst, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21205 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Channing Lab, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Platz, EA (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Room E6138,615 N Wolfe St, Baltimore, MD 21205 USA. EM eplatz@jhsph.edu FU NCI NIH HHS [CA55075]; NHLBI NIH HHS [HL35464]; NIAAA NIH HHS [AA11181] NR 63 TC 45 Z9 47 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD MAR 1 PY 2004 VL 159 IS 5 BP 444 EP 453 DI 10.1093/aje/kwh062 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 800WM UT WOS:000220058400002 PM 14977640 ER PT J AU Zheng, TZ Holford, TR Leaderer, B Zhang, YW Zahm, SH Flynn, S Tallini, G Zhang, B Zhou, KY Owens, PH Lan, Q Rothman, N Boyle, P AF Zheng, TZ Holford, TR Leaderer, B Zhang, YW Zahm, SH Flynn, S Tallini, G Zhang, B Zhou, KY Owens, PH Lan, Q Rothman, N Boyle, P TI Diet and nutrient intakes and risk of non-Hodgkin's lymphoma in Connecticut women SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE case-control studies; diet; dietary fats; lymphoma, non-Hodgkin; proteins; risk factors; women ID VITAMIN SUPPLEMENT USE; TIME TRENDS; UNITED-STATES; LEUKEMIA; PROTEIN; MEN AB A population-based case-control study (601 cases and 717 controls) was conducted in 1995-2001 among Connecticut women to evaluate the relation between diet and nutrient intakes and the risk of non-Hodgkin's lymphoma (NHL). When the highest quartile of intake was compared with the lowest, the authors found an increased risk of NHL associated with animal protein (odds ratio = 1.7, 95% confidence interval: 1.2, 2.4) and saturated fat (odds ratio = 1.9, 95% confidence interval: 1.1, 2.3) but a reduced risk for polyunsaturated fat (odds ratio = 0.6, 95% confidence interval: 0.4, 0.9) and no relation for vegetable protein and monounsaturated fat. An increased risk was also observed for higher intakes of retinol, eggs, and dairy products. On the other hand, a reduced risk was found for higher intakes of dietary fiber and for several fruit and vegetable items. Risk of NHL associated with diet and nutrient intakes appeared to vary based on NHL subtype. An association between dietary intake and NHL risk is biologically plausible because diets high in protein and fat may lead to altered immunocompetence, resulting in an increased risk of NHL. The antioxidant or inhibiting nitrosation reaction properties of vegetables and fruits may result in a reduced risk. Further investigation of the role of dietary intakes on the risk of NHL is warranted. C1 Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06510 USA. McGill Univ, Dept Epidemiol & Biostat, Montreal, PQ, Canada. Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06510 USA. European Inst Oncol, Dept Epidemiol & Biostat, Milan, Italy. RP Zheng, TZ (reprint author), 129 Church St,Suite 700, New Haven, CT 06510 USA. EM tongzhang.zheng@yale.edu RI Boyle, Peter/A-4380-2014; OI Boyle, Peter/0000-0001-6251-0610; Tallini, Giovanni/0000-0003-0113-6682 FU NCI NIH HHS [CA62006-05] NR 33 TC 90 Z9 91 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD MAR 1 PY 2004 VL 159 IS 5 BP 454 EP 466 DI 10.1093/aje/kwh067 PG 13 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 800WM UT WOS:000220058400003 PM 14977641 ER PT J AU Kirk, GD de Sanjose, S Ott, M AF Kirk, GD de Sanjose, S Ott, M CA Epilymph-Spain Study Grp TI Impact of race on the association between diabetes and HCV SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Letter ID C VIRUS-INFECTION; HEPATITIS-C; MELLITUS; PREVALENCE C1 NCI, Viral Epidemiol Branch, NIH, DHHS, Bethesda, MD 20892 USA. Inst Catala Oncol, Barcelona, Spain. Univ Calif San Francisco, Gladstone Inst Virol & Immunol, San Francisco, CA 94143 USA. RP Kirk, GD (reprint author), NCI, Viral Epidemiol Branch, NIH, DHHS, Bethesda, MD 20892 USA. RI Kirk, Gregory/A-8484-2009; de Sanjose Llongueras, Silvia/H-6339-2014 NR 8 TC 1 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 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD MAR PY 2004 VL 99 IS 3 BP 564 EP 564 DI 10.1111/j.1572-0241.2004.04068.x PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 805QR UT WOS:000220381300030 PM 15056103 ER PT J AU Hediger, ML Overpeck, MD Scheidt, PC Ledsky, R Ramcharran, D AF Hediger, ML Overpeck, MD Scheidt, PC Ledsky, R Ramcharran, D TI Pubertal status and risk behaviors in US adolescents: findings from the Health Behaviour in School-aged Children survey. SO AMERICAN JOURNAL OF HUMAN BIOLOGY LA English DT Meeting Abstract C1 NICHD, DESPR, NIH, US Dept HHS, Bethesda, MD USA. NR 0 TC 0 Z9 0 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 1042-0533 J9 AM J HUM BIOL JI Am. J. Hum. Biol. PD MAR-APR PY 2004 VL 16 IS 2 MA 31 BP 207 EP 208 PG 2 WC Anthropology; Biology SC Anthropology; Life Sciences & Biomedicine - Other Topics GA 800CL UT WOS:000220006400044 ER PT J AU Adegoke, OJ Blair, A Shu, XO Sanderson, M Addy, CL Dosemeci, M Zheng, W AF Adegoke, OJ Blair, A Shu, XO Sanderson, M Addy, CL Dosemeci, M Zheng, W TI Agreement of job-exposure matrix (JEM) assessed exposure and self-reported exposure among adult leukemia patients and controls in Shanghai SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE agreement; job-exposure matrix; self-report; occupational exposures; leukemia; Shanghai ID OCCUPATIONAL-EXPOSURE; RETROSPECTIVE ASSESSMENT; LUNG-CANCER; WORKERS; COHORT; CHINA; TERM AB Background Estimating a person's history of occupational exposure in case-control studies is difficult. Methods Percent agreement between selected self-reported occupational exposures and job-exposure matrix (JEM) exposure assessment for all participants and various subgroups of a population-based case-control interview study of 486 leukemia subjects and 502 healthy controls in Shanghai was evaluated. Results With JEM as the "gold standard," the sensitivities for self-reported exposures ranged from 0.75 to 0.98. However, that for pesticide exposure was 0.44 in subjects >51 years old. Self-reported exposures specificities ranged from 0.87 to 0.99. Agreement between self-reported exposures and JEM assessment was good (kappa coefficients [kappa]: 0.48-0.84). Variations in agreement for benzene exposure between males and females as well as between the direct interview and surrogate interview subgroups were observed. Conclusions The levels of agreement between self-report and JEM in this study suggest that self-reported exposures are a suitable method for assessing occupational exposures in this population. (C) 2004 Wiley-Liss, Inc. C1 Meharry Med Coll, Sch Med, Dept Surg, Nashville, TN 37208 USA. NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20850 USA. Vanderbilt Univ, Dept Med, Nashville, TN 37232 USA. Vanderbilt Univ, Vanderbilt Ingram Canc Ctr, Nashville, TN 37232 USA. Univ Texas, Sch Publ Hlth, Brownsville, TX 78520 USA. Univ S Carolina, Norman J Arnold Sch Publ Hlth, Dept Epidemiol & Biostat, Columbia, SC 29208 USA. RP Adegoke, OJ (reprint author), Meharry Med Coll, Sch Med, Dept Surg, 1005 Dr DB Todd Jr Blvd, Nashville, TN 37208 USA. EM oadegoke@mmc.edu FU AHRQ HHS [R24HS116401-01RISP]; NCI NIH HHS [1U54-CA9140801] NR 23 TC 9 Z9 10 U1 3 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD MAR PY 2004 VL 45 IS 3 BP 281 EP 288 DI 10.1002/ajim.10351 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 804GZ UT WOS:000220288500007 PM 14991855 ER PT J AU Gibb, HJ Lees, PSJ Pinsky, P AF Gibb, HJ Lees, PSJ Pinsky, P TI Re: The carcinogenicity risk assessment of chromium compounds SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Letter C1 US EPA, Natl Ctr Environm Assessment, Washington, DC 20460 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD 21218 USA. NCI, Bethesda, MD 20892 USA. RP Gibb, HJ (reprint author), US EPA, Natl Ctr Environm Assessment, 8601D,1200 Penn Ave NW, Washington, DC 20460 USA. EM gibb.herman@epa.gov NR 4 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD MAR PY 2004 VL 45 IS 3 BP 310 EP 310 DI 10.1002/ajim.10338 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 804GZ UT WOS:000220288500012 ER PT J AU Hay, BN Martin, JE Karp, B Davis, J Darnell, D Solomon, B Turner, M Holland, SM Puck, JM AF Hay, BN Martin, JE Karp, B Davis, J Darnell, D Solomon, B Turner, M Holland, SM Puck, JM TI Familial immunodeficiency vasculitis, myoclonus, and with cutaneous cognitive impairment SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE immunodeficiency; myoclonus; vasculitis ID HYPER-IGE SYNDROME; RECURRENT INFECTIONS; CHOLESTEROL; CHROMOSOME; POPULATION; DELETION; PATIENT; MEN AB We report a family with five of six siblings (including identical male twins) with a novel constellation of immunologic and neurologic impairments. Affected subjects experienced severe dermatitis starting around 9 months of age, Stevens-Johnson syndrome in early childhood, and extreme elevations of IgE (9,400-43,000 IU/ml). The oldest sibling died at age 27 of respiratory failure following recurrent, severe pneumonias. All four surviving affected siblings have had chronic sinusitis or otitis, cutaneous vasculitis, and recurrent bacterial pneumonias leading to bronchiectasis. Neurologic features in all five siblings included oral motor deficits, dysarthria, low average IQ (70-80), and essential myoclonus. Four had documented ataxia and/or mild sensory loss with increased patellar but diminished ankle reflexes. The nonconsanguineous parents and one sibling had none of the above findings, consistent with autosomal recessive inheritance. This primary immunodeficiency with distinctive neurological impairments represents a new syndrome. Published 2003 Wiley-Liss, Inc.(dagger) C1 NHGRI, NIH, Bethesda, MD 20892 USA. NIAID, NIH, Bethesda, MD 20892 USA. NINDS, NIH, Bethesda, MD 20892 USA. NIH, Warren G Magnuson Clin Ctr, Dept Rehabil Med, Speech Pathol Sect, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. RP Puck, JM (reprint author), NHGRI, NIH, Bldg 49,Room 4A14,49 Convent Dr, Bethesda, MD 20892 USA. EM jpuck@mail.nih.gov NR 18 TC 6 Z9 6 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 0148-7299 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD MAR 1 PY 2004 VL 125A IS 2 BP 145 EP 151 DI 10.1002/ajmg.a.20595 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 800CZ UT WOS:000220007800005 PM 14981714 ER PT J AU Levine, RJ Qian, C LeShane, ES Yu, KF England, LJ Schisterman, EF Wataganara, T Romero, R Bianchi, DW AF Levine, RJ Qian, C LeShane, ES Yu, KF England, LJ Schisterman, EF Wataganara, T Romero, R Bianchi, DW TI Two-stage elevation of cell-free fetal DNA in maternal sera before onset of preeclampsia SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE cell-free fetal DNA; C-reactive protein; preeclampsia; placenta; inflammation ID DEVELOP PREECLAMPSIA; OXIDATIVE STRESS; PREGNANT-WOMEN; HUMAN PLACENTA; PLASMA; CLEARANCE; CALCIUM; TRIAL AB Objective: The purpose was to determine Whether preeclampsia (PE) is caused by microfragments of syncytial trophoblast shed into the maternal circulation that stimulate an exaggerated inflammatory response. Study design: A nested case control study was performed within the Calcium for Preeclampsia Prevention trial cohort of healthy nulliparous women. Each preeclampsia case was matched to I normotensive control. One hundred twenty pairs were randomly chosen for analysis of serum cell-free fetal DNA (cffDNA), a marker of placental debris, and C-reactive protein (CRP), a marker of inflammation, in all 658 specimens obtained before labor. Results: At 29 to 41 weeks of gestation, cffDNA concentrations were significantly higher after preeclampsia than before (219 vs 112 genome equivalents [GE]/mL, P <.001). Before preeclampsia, cffDNA in cases exceeded controls at 17 to 28 weeks (36 vs 16 GE/mL, P<.001), but at 29 to 41 weeks, only within 3 weeks before preeclampsia (176 vs 75 GE/mL, P<.001). CRP serum concentrations were neither associated with cffDNA nor elevated before preeclampsia. Conclusion: Preeclampsia is accompanied by a 2-stage elevation of fetal DNA, but not by elevation of CRP. Elevated cffDNA at 17 to 28 weeks may be due toplacental necrosis and apoptosis. Subsequent elevations may reflect impaired DNA elimination. The 2-stage elevation suggests the possibility of measurement of fetal DNA both to screen for preeclampsia, and to indicate impending clinical disease. (C) 2004 Elsevier Inc. All rights reserved. C1 NICHHD, Div Epidemiol Stat & Prevent Res, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. Allied Technol Grp, Rockville, MD USA. Tufts Univ, New England Med Ctr, Dept Pediat, Div Genet, Boston, MA 02111 USA. Tufts Univ, New England Med Ctr, Dept Obstet & Gynecol, Div Genet, Boston, MA 02111 USA. Tufts Univ, Sch Med, Boston, MA 02111 USA. NICHHD, Dept Hlth & Human Serv, Perinatol Res Branch, Detroit, MI USA. RP Levine, RJ (reprint author), NICHHD, Div Epidemiol Stat & Prevent Res, Dept Hlth & Human Serv, NIH, Bldg 6100,Room 7B03, Bethesda, MD 20892 USA. EM LevineRJ@mail.nih.gov OI Wataganara, Tuangsit/0000-0001-7172-053X; Schisterman, Enrique/0000-0003-3757-641X FU NICHD NIH HHS [N01-HD-1-3121, N01-HD-2-3154, N01-HD-5-3246] NR 28 TC 128 Z9 142 U1 1 U2 4 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD MAR PY 2004 VL 190 IS 3 BP 707 EP 713 DI 10.1016/j.ajog.2003.12.019 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 808OH UT WOS:000220577900020 PM 15042003 ER PT J AU Dombrowski, MP Schatz, M Wise, R Thom, EA Landon, M Mabie, W Newman, RB McNellis, D Hauth, JC Lindheimer, M Caritis, SN Leveno, KJ Meis, P Miodovnik, M Wapner, RJ Varner, MW O'Sullivan, MJ Conway, DL AF Dombrowski, MP Schatz, M Wise, R Thom, EA Landon, M Mabie, W Newman, RB McNellis, D Hauth, JC Lindheimer, M Caritis, SN Leveno, KJ Meis, P Miodovnik, M Wapner, RJ Varner, MW O'Sullivan, MJ Conway, DL CA Natl Inst Child Hlth Human Dev Mat Natl Heart Lung Blood Inst TI Randomized trial of inhaled beclomethasone dipropionate versus theophylline for moderate asthma during pregnancy SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 21st Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 05-10, 2001 CL RENO, NV SP Soc Maternal Fetal Med ID BUDESONIDE; MILD; MECHANISMS; MORBIDITY; SEVERITY AB Objective: This study was undertaken to compare the efficacy of inhaled beclomethasone dipropionate to oral theophylline for the prevention of asthma exacerbation(s) requiring medical intervention. Study design: A prospective, double-blind, double placebo-controlled randomized clinical trial of pregnant women with moderate asthma was performed. Results: There was no significant difference (P = .554) in the proportion of asthma exacerbations among the 194 women in the beclomethasone cohort (18.0%) versus the 191 in the theophylline cohort (20.4%; risk ratio [RR] = 0.9, 95% CI = 0:6-1.3). The beclomethasone cohort had significantly lower incidences of discontinuing study medications caused by side effects (RR = 0.3, 95% CI = 0.1-0.9; P = .016), and proportion of study visits with forced expiratory volume expired in 1 second (FEV1) less than 80% predicted (0.284 +/- 0.331 vs 0.284 +/- 0.221, P = .039). There were no significant differences in treatment failure, compliance, or proportion of peak expiratory flow rate less than 80% predicted. There were no significant differences in maternal or perinatal outcomes. Conclusion: The treatment of moderate asthma with inhaled beclomethasone versus oral theophylline resulted in similar rates of asthma exacerbations and similar obstetric and perinatal outcomes. These results favor the use of inhaled corticosteroids for moderate asthma during pregnancy because of the improved FEV1 and because theophylline had more side effects and requires serum monitoring. (C) 2004 Elsevier Inc. All rights reserved. C1 Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA. Kaiser Permanente, Dept Allergy, San Diego, CA USA. Johns Hopkins Univ, Dept Pulm Med, Baltimore, MD USA. George Washington Univ, Ctr Biostat, Washington, DC USA. Ohio State Univ, Dept Obstet & Gynecol, Columbus, OH 43210 USA. Univ Tennessee, Memphis, TN USA. Med Coll S Carolina, Dept Obstet & Gynecol, Charleston, SC USA. NICHHD, Bethesda, MD 20892 USA. Univ Alabama, Dept Obstet & Gynecol, Birmingham, AL 35294 USA. Univ Chicago, Dept Obstet & Gynecol, Chicago, IL 60637 USA. Univ Pittsburgh, Magee Womens Hosp, Dept Obstet & Gynecol, Pittsburgh, PA 15213 USA. Univ Texas, SW Med Ctr, Dept Obstet & Gynecol, Dallas, TX 75235 USA. Wake Forest Univ, Dept Obstet & Gynecol, Winston Salem, NC 27109 USA. Univ Cincinnati, Dept Obstet & Gynecol, Cincinnati, OH USA. Thomas Jefferson Univ, Dept Obstet & Gynecol, Philadelphia, PA 19107 USA. Univ Utah, Dept Obstet & Gynecol, Salt Lake City, UT USA. Univ Miami, Dept Obstet & Gynecol, Miami, FL 33152 USA. Univ Texas, Dept Obstet & Gynecol, San Antonio, TX 78285 USA. RP Dombrowski, MP (reprint author), St Johns Hosp, Dept Obstet & Gynecol, 22151 Moross Rd,Suite 313, Detroit, MI 48236 USA. EM Mitchell.Dombrowski@stjohn.org RI Varner, Michael/K-9890-2013 OI caritis, steve/0000-0002-2169-0712; Wise, Robert/0000-0002-8353-2349; Varner, Michael/0000-0001-9455-3973 FU NICHD NIH HHS [HD34122, HD21410, HD21414, HD21434, HD27860, HD27861, HD27869, HD27883, HD27889, HD27905, HD27915, HD27917, HD34116, HD34136, HD34208, HD36801] NR 24 TC 52 Z9 56 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD MAR PY 2004 VL 190 IS 3 BP 737 EP 744 DI 10.1016/j.ajog.2003.09.071 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 808OH UT WOS:000220577900024 PM 15042007 ER PT J AU How, HY Sibai, B Lindheimer, M Caritis, S Hauth, J Klebanoff, M MacPherson, C Van Dorsten, P Miodovnik, M Landon, M Paul, R Meis, P Thurnau, G Dombrowski, M Robertsf, J AF How, HY Sibai, B Lindheimer, M Caritis, S Hauth, J Klebanoff, M MacPherson, C Van Dorsten, P Miodovnik, M Landon, M Paul, R Meis, P Thurnau, G Dombrowski, M Robertsf, J TI Is early-pregnancy proteinuria associated with an increased rate of preeclampsia in women with pregestational diabetes mellitus? SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE early-pregnancy proteinuria; pregestational diabetes mellitus; preeclampsia ID URINARY ALBUMIN EXCRETION; CEREBROSPINAL-FLUID; HYPERTENSION AB Objective: The purpose of this study was to determine whether the rate of preeclampsia in pregnant diabetic women is increased in those women with early-pregnancy proteinuria of 190 to 499 mg/24 hours compared with women with proteinuria of < 190 mg/24 hours. Study design: Secondary analysis was performed with relevant data from 194 pregnant women with type 1 and type 2 diabetes mellitus whose condition required insulin and who were enrolled previously in a multicenter trial of low-dose aspirin for the prevention of preeclampsia. The women Were assigned to 1 of 3 groups, based on the level of proteinuria at enrollment (13-26 weeks of gestation). Group 1 comprised women with < 190 mg protein/24 hours (n = 94); group 2 comprised women with 190 to 499 mg protein/24 hours (n = 35); and group 3 comprised women with greater than or equal to 500 mg protein/24 hours (n = 65). The rate of preeclampsia, according to strict predefined criteria, was then determined. Results: The rate of preeclampsia, was not increased statistically significantly in patients with early-pregnancy proteinuria of 190 to 499 mg/24 hours (7/35 women; 20%) when compared with women with proteinuria, of < 190 mg/24 hours (16/94 women; 17%). Conclusion: We did not find an increased rate of preeclampsia in women with pregestational diabetes mellitus with early-pregnancy proteinuria of 190 to 499 mg/24 hours when compared with women with pregestational diabetes mellitus with proteinuria of < 190 mg/24 hours. (C) 2004 Elsevier Inc. All rights reserved. C1 NICHD, Network Maternal Fetal Med Units, Bethesda, MD USA. RP How, HY (reprint author), NICHD, Network Maternal Fetal Med Units, Bethesda, MD USA. OI caritis, steve/0000-0002-2169-0712 FU NICHD NIH HHS [HD19897, HD21410, HD21414, HD21434, HD27860, HD27861, HD27869, HD27883, HD27889, HD27905, HD27915, HD27917, HD36801] NR 15 TC 6 Z9 7 U1 1 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD MAR PY 2004 VL 190 IS 3 BP 775 EP 778 DI 10.1016/j.ajog.2003.11.031 PG 4 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 808OH UT WOS:000220577900030 PM 15042013 ER PT J AU Al-Attar, L Berrocal, A Warman, R Dubovy, S Paredes, A Chan, CC Davis, J AF Al-Attar, L Berrocal, A Warman, R Dubovy, S Paredes, A Chan, CC Davis, J TI Diagnosis by polymerase chain reaction of ocular posttransplant lymphoproliferative disorder after pediatric renal transplantation SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID DNA; INFECTION AB PURPOSE: To report diagnosis by polymerase chain reaction of intraocular posttransplant lymphoproliferative disorder in a pediatric renal transplant patient. DESIGN: Observational case report. METHODS: Retrospective review. RESULTS: An 11-year-old girl developed infectious mono. nucleosis 15 months after renal transplantation for focal segmental sclerosis. Papillitis and hypopyon uveitis developed 8 months later, followed by iris nodules. Diagnosis of intraocular posttransplant lymphoproliferative disorder was made by polymerase chain reaction of aqueous humor for Epstein-Barr virus and confirmed by histopathology of an iris biopsy specimen. Infiltrating iris lymphocytes in the biopsy specimen were positive for Epstein-Barr DNA. Polymerase chain reaction also revealed gene rearrangement of the variable region of the heavy immunoglobulin chain, consistent with a monoclonal B-lymphocyte population. Iris nodules resolved with reduction in immunosuppressive medication. CONCLUSION: Polymerase chain reaction for Epstein-Barr virus may be helpful in diagnosis of intraocular posttransplant lymphoproliferative disorder. (C) 2004 by Elsevier Inc. All rights reserved. C1 Univ Miami, Bascom Palmer Eye Inst, Sch Med, Dept Ophthalmol, Miami, FL 33136 USA. Miami Childrens Hosp, Miami, FL USA. NEI, Immunol Lab, Bethesda, MD 20892 USA. RP Davis, J (reprint author), Univ Miami, Bascom Palmer Eye Inst, Sch Med, Dept Ophthalmol, 900 NW 17th St, Miami, FL 33136 USA. EM jdavis@med.miami.edu NR 6 TC 5 Z9 5 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD MAR PY 2004 VL 137 IS 3 BP 569 EP 571 DI 10.1016/j.ajo.2003.08.013 PG 3 WC Ophthalmology SC Ophthalmology GA 804VF UT WOS:000220325500031 PM 15013889 ER PT J AU Andrade, RE Muccioli, C Farah, ME Nussenblatt, RB Belfort, R AF Andrade, RE Muccioli, C Farah, ME Nussenblatt, RB Belfort, R TI Intravitreal triamcinolone in the treatment of serous retinal detachment in Vogt-Koyanagi-Harada syndrome SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID UVEITIS; DISEASE AB PURPOSE: To report the use of intravitreal injection of acetonide during the acute phase of Vogt-Koyanagi-Harada disease. DESIGN: Prospective interventional case series. METHODS: Three eyes from two patients at the acute phase of Vogt-Koyanagi-Harada disease with serous retinal detachments were treated with a 4-mg intravitreal injection of triamcinolone acetonide. The following variables were evaluated: visual acuity, intraocular pressure, and height of the serous retinal detachment using optical coherence tomography. RESULTS: The optical coherence tomography images showed a marked decrease in the retinal detachment in the first week after the injection with subsequent return to normal retinal thickness in all eyes. CONCLUSIONS: Intravitreal triamcinolone acetonide provides short-term improvement in visual acuity and serous retinal detachments associated with Vogt-Koyanagi-Harada disease. These findings should be followed by future studies to evaluate long-term effects. (C) 2004 by Elsevier Inc. All rights reserved. C1 Univ Fed Sao Paulo, Dept Ophthalmol, IPEPO, Inst Visao, Sao Paulo, Brazil. NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Andrade, RE (reprint author), Av Dr Altino Arantes 574,Ap 83, BR-04042003 Sao Paulo, Brazil. EM rafaelernane@uol.com.br RI Belfort Jr, Rubens/E-2252-2012; Muccioli, Cristina/C-3419-2013 OI Belfort Jr, Rubens/0000-0002-8422-3898; NR 4 TC 46 Z9 52 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD MAR PY 2004 VL 137 IS 3 BP 572 EP 574 DI 10.1016/j.ajo.2003.08.035 PG 3 WC Ophthalmology SC Ophthalmology GA 804VF UT WOS:000220325500032 PM 15013890 ER PT J AU Gujral, JS Liu, J Farhood, A Hinson, JA Jaeschke, H AF Gujral, JS Liu, J Farhood, A Hinson, JA Jaeschke, H TI Functional importance of ICAM-1 in the mechanism of neutrophil-induced liver injury in bile duct-ligated mice SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE hepatotoxicity; chlorotyrosine-protein adducts; 4-hydroxynonenal adducts; oxidant stress ID INTERCELLULAR-ADHESION MOLECULE-1; ISCHEMIA-REPERFUSION INJURY; MURINE ENDOTOXIN-SHOCK; TUMOR-NECROSIS-FACTOR; PEROXIDASE-DEFICIENT MICE; PARENCHYMAL-CELL INJURY; BILIARY OBSTRUCTION; RAT-LIVER; LEUKOCYTE RECRUITMENT; LIPID-PEROXIDATION AB Cholestasis-induced liver injury during bile duct obstruction causes an acute inflammatory response. To further characterize the mechanisms underlying the neutrophil-induced cell damage in the bile duct ligation (BDL) model, we performed experiments using wild-type (WT) and ICAM-1-deficient mice. After BDL for 3 days, increased ICAM-1 expression was observed along sinusoids, along portal veins, and on hepatocytes in livers of WT animals. Neutrophils accumulated in sinusoids [358 +/- 44 neutrophils/20 high-power fields (HPF)] and >50% extravasated into the parenchymal tissue. Plasma alanine transaminase (ALT) levels increased by 23-fold, and severe liver cell necrosis (47 +/- 11% of total cells) was observed. Chlorotyrosine-protein adducts (a marker for neutrophil-derived hypochlorous acid) and 4-hydroxynonenal adducts (a lipid peroxidation product) were detected in these livers. Neutrophils also accumulated in the portal venules and extravasated into the portal tracts. However, no evidence for chlorotyrosine or 4-hydroxynonenal protein adducts was detected in portal tracts. ICAM-1-deficient mice showed 67% reduction in plasma ALT levels and 83% reduction in necrosis after BDL compared with WT animals. The total number of neutrophils in the liver was reduced (126 +/- 25/20 HPF), and 85% of these leukocytes remained in sinusoids. Moreover, these livers showed minimal staining for chlorotyrosine and 4-hydroxynonenal adducts, indicating a substantially reduced oxidant stress and a diminished cytokine response. Thus neutrophils relevant for the aggravation of acute cholestatic liver injury in BDL mice accumulate in hepatic sinusoids, extravasate into the tissue dependent on ICAM-1, and cause cell damage involving reactive oxygen formation. C1 Univ Arizona, Coll Med, Liver Res Inst, Tucson, AZ 85724 USA. Univ Arkansas Med Sci, Dept Pharmacol & Toxicol, Little Rock, AR 72205 USA. NIEHS, Inorgan Carcinogenesis Sect, NCI, Res Triangle Pk, NC 27709 USA. Univ Texas, Hlth Sci Ctr, Dept Pathol, Houston, TX 77030 USA. RP Jaeschke, H (reprint author), Univ Arizona, Coll Med, Liver Res Inst, 1501 N Campbell Ave,Rm 6309, Tucson, AZ 85724 USA. EM Jaeschke@email.arizona.edu FU NIAAA NIH HHS [AA-12916]; NIGMS NIH HHS [GM-58884] NR 55 TC 81 Z9 86 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD MAR PY 2004 VL 286 IS 3 BP G499 EP G507 DI 10.1152/ajpgi.00318.2003 PG 9 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 771KD UT WOS:000188783400017 PM 14563671 ER PT J AU Ahn, D Cheng, L Moon, C Spurgeon, H Lakatta, EG Talan, MI AF Ahn, D Cheng, L Moon, C Spurgeon, H Lakatta, EG Talan, MI TI Induction of myocardial infarcts of a predictable size and location by branch pattern probability-assisted coronary ligation in C57BL/6 mice SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE heart; anatomy; method; cardiovascular physiology ID LEFT-VENTRICULAR FUNCTION; ECHOCARDIOGRAPHIC-ASSESSMENT; MURINE MODEL; MOUSE; HEART; EVOLUTION AB The ability to create experimental myocardial infarctions of reproducible size and location is tantamount to progress in multiple facets of ischemic heart disease research. Branches of the mouse left main descending coronary artery penetrate the myocardium close to their origin and require "blind" ligation. Our objective was to develop a technique for ligation of nonvisible coronary artery branches to permit the reliable creation of infarcts of uniformly small size and location. From latex castings of the left coronary artery of C57BL/6J mice (n = 53), we calculated the highest probability for the location of branch points of two of three left ventricular (LV) branches distal to the origin of the left main descending artery. On the basis of these anatomic probabilities, we blindly ligated two areas that were likely to be locations of these nonvisible LV branches. We were successful in producing two types of small transmural myocardial infarctions (16.04 +/- 3.64 and 4.68 +/- 1.47% of the LV) in 57% of attempts. Thus our branch pattern probability-assisted method permits routine creation of small infarcts of uniform size in the mouse. C1 NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP Talan, MI (reprint author), NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM talanm@grc.nia.nih.gov NR 18 TC 32 Z9 33 U1 1 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 EI 1522-1539 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD MAR PY 2004 VL 286 IS 3 BP H1201 EP H1207 DI 10.1152/ajpheart.00862.2003 PG 7 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 771KB UT WOS:000188783200049 PM 14766681 ER PT J AU Morrison, LE Whittaker, RJ Klepper, RE Wawrousek, EF Glembotski, CC AF Morrison, LE Whittaker, RJ Klepper, RE Wawrousek, EF Glembotski, CC TI Roles for alpha B-crystallin and HSPB2 in protecting the myocardium from ischemia-reperfusion-induced damage in a KO mouse model SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE small heat shock protein; necrosis; apoptosis; glutathione; knockout mouse ID HEAT-SHOCK-PROTEIN; INDUCED CELL-DEATH; TNF-ALPHA; RABBIT CARDIOMYOCYTES; GLUTATHIONE LEVELS; CARDIAC MYOCYTES; OXIDATIVE STRESS; SKELETAL-MUSCLE; A-CRYSTALLIN; PHOSPHORYLATION AB Overexpression studies have shown that the small heat shock proteins (sHSP) protect the myocardium from ischemia-reperfusion (I/R)-induced damage. However, gene deletion studies are necessary to demonstrate whether sHSPs are required for protection. The genes for alphaB-crystallin (alphaBC) and HSPB2, two sHSPs that are expressed in high levels in the heart, are in close proximity to one another; as a result, both genes were disrupted in a recently generated knockout (KO) mouse line. The alphaBC/HSPB2 KO mouse line is currently the only model that features disruption of sHSPs normally expressed in the heart. Accordingly, we examined the cardiac morphology, function, and response to I/R-induced stress in alphaBC-HSPB2 KO mice. Initial gross, light microscopic and echocardiographic characterization showed that the morphological and functional properties of hearts from adult KO mice were indistinguishable from age-matched wild-type (WT) mice. Electron microscopy showed that, compared with WT mouse hearts, KO mouse heart sarcomeres were relatively normal. Isolated perfused KO mouse hearts displayed normal contractility; however, when compared with WT, after I/R, KO mouse hearts exhibited a twofold reduction in contractile recovery, as well as increased necrosis and apoptosis. Additionally, when compared with WT, KO mouse hearts exhibited 43% less reduced glutathione, which is known to protect from I/R-induced damage. Thus, whereas neither alphaBC nor HSPB2 is essential for myocardial development and function under nonstressful conditions, one or both are required for maximal functional recovery and protection from I/R-induced necrosis and apoptosis. C1 San Diego State Univ, Dept Biol, San Diego, CA 92182 USA. San Diego State Univ, Inst Heart, San Diego, CA 92182 USA. NEI, NIH, Bethesda, MD 20892 USA. RP Glembotski, CC (reprint author), San Diego State Univ, Dept Biol, San Diego, CA 92182 USA. EM cglembotski@sciences.sdsu.edu RI Wawrousek, Eric/A-4547-2008 FU NHLBI NIH HHS [HL-63975]; NINDS NIH HHS [NS/HL-25037] NR 54 TC 69 Z9 78 U1 1 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 EI 1522-1539 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD MAR PY 2004 VL 286 IS 3 BP H847 EP H855 DI 10.1152/ajpheart.00715.2003 PG 9 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 771KB UT WOS:000188783200005 PM 14592939 ER PT J AU Spencer, LT Paone, G Krein, PM Rouhani, FN Rivera-Nieves, J Brantly, ML AF Spencer, LT Paone, G Krein, PM Rouhani, FN Rivera-Nieves, J Brantly, ML TI Role of human neutrophil peptides in lung inflammation associated with alpha(1)-antitrypsin deficiency SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE pulmonary emphysema; granulocytes; alveolar macrophages; serpins ID BRONCHOALVEOLAR LAVAGE FLUID; EPITHELIAL LINING FLUID; ALVEOLAR MACROPHAGES; CYSTIC-FIBROSIS; DEFENSINS; ELASTASE; LEUKOTRIENE-B4; CYTOTOXICITY; ANTIBIOTICS; EMPHYSEMA AB Individuals with alpha(1)-antitrypsin (alpha(1)-AT) deficiency are at risk for early-onset destructive lung disease as a result of insufficient lower respiratory tract alpha(1)-AT and an increased burden of neutrophil products such as elastase. Human neutrophil peptides (HNP), the most abundant protein component of neutrophil azurophilic granules, represent another potential inflammatory component in lung disease characterized by increased numbers of activated or deteriorating neutrophils. The purpose of this study was to determine the role of HNP in lower respiratory tract inflammation and destruction occuring in alpha(1)-AT deficiency. alpha(1)-AT-deficient individuals (n = 33) and healthy control subjects (n = 21) were evaluated by bronchoalveolar lavage. HNP concentrations were significantly higher in alpha(1)-AT-deficient individuals ( 1,976 +/- 692 vs. 29 +/- 12 nM, P < 0.0001), and levels correlated with markers of neutrophil-mediated lung inflammation. In vitro, HNP produced a dose-dependent cytotoxic effect on alveolar macrophages and stimulated production of the potent neutrophil chemoattractants leukotriene B-4 and interleukin-8 by alveolar macrophages, with a 6- to 10-fold increase in chemoattractant production over negative control cultures (P < 0.05). A synergistic effect was noted between HNP and neutrophil elastase with regard to leukotriene B-4 production. Importantly, the proinflammatory effects of HNP were blocked by alpha(1)-AT. HNP likely play an important role in amplifying and maintaining neutrophil-mediated inflammation in the lungs. C1 Univ Florida, Coll Med, Dept Pediat, Div Pulm Dis, Gainesville, FL 32610 USA. Univ Florida, Coll Med, Dept Med, Div Pulm & Crit Care Med, Gainesville, FL 32610 USA. NHLBI, Clin Studies Sect, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. RP Spencer, LT (reprint author), Univ Florida, Coll Med, Dept Pediat, Div Pulm Dis, POB 100296, Gainesville, FL 32610 USA. EM spenclt@peds.ufl.edu FU NHLBI NIH HHS [IZ01 HL-002538, 1K23 HL -04213, 1K24 HL-04456001AA2N] NR 23 TC 58 Z9 61 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD MAR 1 PY 2004 VL 286 IS 3 BP L514 EP L520 DI 10.1152/ajplung.00099.2003 PG 7 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 770TL UT WOS:000188746900009 PM 14594730 ER PT J AU Tarpey, MM Wink, DA Grisham, MB AF Tarpey, MM Wink, DA Grisham, MB TI Methods for detection of reactive metabolites of oxygen and nitrogen: in vitro and in vivo considerations SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Review DE free radical; nitric oxide; superoxide; hydrogen peroxide; peroxynitrite ID ELECTRON-SPIN-RESONANCE; CYPRIDINA LUCIFERIN ANALOG; MANGANESE SUPEROXIDE-DISMUTASE; OXIDATIVE STRESS MEASUREMENTS; POLYUNSATURATED FATTY-ACIDS; FREE-RADICAL FORMATION; NITRIC-OXIDE SYNTHASE; HYDROGEN-PEROXIDE; ENDOTHELIAL-CELLS; CYTOCHROME-C AB Facile detection of reactive oxygen and nitrogen species in biologic systems is often problematic. This is a result of the numerous cellular mechanisms, both enzymatic and nonenzymatic involved in their catabolism/decomposition, the complex and overlapping nature of their reactivities, as well as the often limited intracellular access of detector systems. This review describes approaches to the direct and indirect measurement of different reactive metabolites of oxygen and nitrogen. Particular attention to a method's applicability for in vivo determinations will be addressed. C1 Louisiana State Univ, Hlth Sci Ctr, Dept Cellular & Mol Physiol, Shreveport, LA 71130 USA. Univ Alabama, Dept Anesthesiol, Birmingham, AL 35294 USA. Univ Alabama, Ctr Free Rad Biol, Birmingham, AL 35294 USA. NCI, Radiat Biol Branch, Bethesda, MD 20814 USA. RP Grisham, MB (reprint author), Louisiana State Univ, Hlth Sci Ctr, Dept Cellular & Mol Physiol, 1501 Kings Highway, Shreveport, LA 71130 USA. EM mgrish@lsuhsc.edu FU NHLBI NIH HHS [HL-66110]; NIDDK NIH HHS [DK-43785, DK-64023] NR 147 TC 307 Z9 320 U1 4 U2 50 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD MAR 1 PY 2004 VL 286 IS 3 BP R431 EP R444 DI 10.1152/ajpregu.00361.2003 PG 14 WC Physiology SC Physiology GA 770TQ UT WOS:000188747300002 PM 14761864 ER PT J AU Wang, WD Li, CL Kwon, TH Miller, RT Knepper, MA Frokiaer, J Nielsen, S AF Wang, WD Li, CL Kwon, TH Miller, RT Knepper, MA Frokiaer, J Nielsen, S TI Reduced expression of renal Na(+) transporters in rats with PTH-induced hypercalcemia SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE calcium-sensing receptor; hypercalcemia; parathyroid hormone; sodium transport; urinary concentrating mechanism ID THICK ASCENDING LIMB; CALCIUM-SENSING RECEPTOR; PARATHYROID-HORMONE; SODIUM-TRANSPORT; PROXIMAL TUBULE; I-COTRANSPORTERS; REABSORPTION; KIDNEY; CAMP; INHIBITION AB The purpose of this study was to evaluate whether the natriuresis and polyuria seen in parathyroid hormone (PTH)-induced hypercalcemia are associated with dysregulation of renal Na transporters. Rats were infused with three different doses of human PTH [PTH (1-34); 7.5, 10, and 15 mug . kg(-1) . day(-1) sc] or vehicle for 48 h using osmotic minipumps. The rats treated with PTH developed significant hypercalcemia ( plasma total calcium levels: 2.71 +/- 0.03, 2.77 +/- 0.02, and 3.42 +/- 0.06 mmol/l, respectively, P < 0.05 compared with corresponding controls). The rats with severe hypercalcemia induced by high-dose PTH developed a decreased glomerular filtration rate (GFR), increased urine output, reduced urinary osmolality, increased urinary Na excretion, and fractional excretion of Na. This was associated with downregulation ( calculated as a fraction of control levels) of whole kidney expression of type 2 Na-P(i) cotransporter (NaPi-2; 16 +/- 6%), type 3 Na/H exchanger (NHE3; 42 +/- 7%), Na-K-ATPase (55 +/- 2%), and bumetanide-sensitive Na-K-2Cl cotransporter (BSC- 1; 25 +/- 4%). In contrast, an upregulation of the Ca(2+)-sensing receptor (CaR) was observed. Rats treated with moderate-dose PTH exhibited unchanged GFR but decreased urinary concentration. The whole kidney expression of NHE3 ( 52 +/- 8%) and NaPi-2 ( 26 +/- 5%) was persistently decreased, whereas BSC- 1 and Na-K-ATPase protein levels were not altered. CaR expression was also increased. Moreover, rats treated with low-dose PTH showed very mild hypercalcemia but unchanged GFR, normal urinary concentration, and unchanged expression of Na transporters and CaR. In conclusion, the reduced expression of major renal Na transporters is likely to play a role in the increased urinary Na excretion and decreased urinary concentration in rats with PTH-induced hypercalcemia. Moreover, the increase in the CaR in the thick ascending limb ( TAL) may indicate a potential role of the CaR in inhibiting Na transport in the TAL. C1 Univ Aarhus, Inst Anat, Water & Salt Res Ctr, DK-8000 Aarhus C, Denmark. Kyungpook Natl Univ, Sch Med, Dept Biochem, Taegu 700422, South Korea. Case Western Reserve Univ, Louis Stokes Vet Affairs Med Ctr, Dept Med, Cleveland, OH 44106 USA. NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. RP Nielsen, S (reprint author), Univ Aarhus, Inst Anat, Water & Salt Res Ctr, Bldg 233, DK-8000 Aarhus C, Denmark. EM sn@ana.au.dk FU Intramural NIH HHS [Z01 HL001285-21, Z99 HL999999] NR 49 TC 24 Z9 24 U1 1 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD MAR 1 PY 2004 VL 286 IS 3 BP F534 EP F545 DI 10.1152/ajprenal.00044.2003 PG 12 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 770DG UT WOS:000188707500014 PM 14625199 ER PT J AU Winterer, G Coppola, R Goldberg, TE Egan, MF Jones, DW Sanchez, CE Weinberger, DR AF Winterer, G Coppola, R Goldberg, TE Egan, MF Jones, DW Sanchez, CE Weinberger, DR TI Prefrontal broadband noise, working memory, and genetic risk for schizophrenia SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Review ID POSITRON-EMISSION TOMOGRAPHY; EVENT-RELATED POTENTIALS; CORTICAL NETWORK MODEL; DELAY-PERIOD ACTIVITY; CEREBRAL BLOOD-FLOW; PHYSIOLOGICAL DYSFUNCTION; INTRACEREBRAL POTENTIALS; VISUAL-STIMULI; RARE TARGET; DOPAMINERGIC MODULATION AB Objective: It has been suggested that increased variability of prefrontal physiological responses may represent a fundamental mechanism underlying frontal lobe deficits in schizophrenia. Increased response variability ("noise") is thought to result from impaired phase resetting of stimulus-induced dynamic changes of ongoing rhythmic oscillations (field potentials) generated in the apical dendrites of pyramidal neurons. In the present study, the authors explored whether this particular physiological abnormality predicts working memory performance and is related to the genetic risk for schizophrenia. Method: Prefrontal response variability of discrete frequency components was investigated across a broad frequency range (0.5-45.0 Hz) during processing of an oddball paradigm in patients with schizophrenia (N=66), their clinically unaffected siblings (N=115), and healthy comparison subjects (N=89). Results: As hypothesized, prefrontal noise was negatively correlated with working memory performance across all subjects. in addition, it was observed that prefrontal noise possesses trait characteristics and is strongly associated with genetic risk for schizophrenia. Conclusions: Frontal lobe-related cognitive function depends on the ability to synchronize cortical pyramidal neurons, which is in part genetically controlled. Increased prefrontal "noise" is an intermediate phenotype related to genetic susceptibility for schizophrenia. C1 NIMH, Unit Mol Neuroimaging, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. RP Winterer, G (reprint author), NIMH, Unit Mol Neuroimaging, Clin Brain Disorders Branch, Bldg 10,Rm 4S229A,MSC 1379, Bethesda, MD 20892 USA. EM wintereg@intra.nimh.nih.gov NR 106 TC 138 Z9 138 U1 0 U2 4 PU AMER PSYCHIATRIC PRESS, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD MAR PY 2004 VL 161 IS 3 BP 490 EP 500 DI 10.1176/appi.ajp.161.3.490 PG 11 WC Psychiatry SC Psychiatry GA 818WU UT WOS:000221276000015 PM 14992975 ER PT J AU Fee, E Brown, TM AF Fee, E Brown, TM TI "An eventful epoch in the history of your lives" SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material C1 NIH, Natl Lib Med, Hist Med Div, Bethesda, MD 20892 USA. Univ Rochester, Dept Hist, Rochester, NY USA. Univ Rochester, Dept Community & Prevent Med, Rochester, NY USA. RP Fee, E (reprint author), Bldg 38,Room 1E21,8600 Rockville Pike, Bethesda, MD 20894 USA. EM elizabeth_fee@nim.nih.gov NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD MAR PY 2004 VL 94 IS 3 BP 367 EP 367 DI 10.2105/AJPH.94.3.367 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 779TQ UT WOS:000189317400005 PM 14998795 ER PT J AU Reyes, L Shelton, M Riggs, M Brown, MB AF Reyes, L Shelton, M Riggs, M Brown, MB TI Rat strains differ in susceptibility to maternal and fetal infection with Mycoplasma pulmonis SO AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY LA English DT Article DE chorioamnionitis; fetal infection; genital mycoplasmosis; Mycoplasma pulmonis ID SPRAGUE-DAWLEY RATS; UREAPLASMA-UREALYTICUM; INFLAMMATORY RESPONSE; PREMATURE RUPTURE; PRETERM; MEMBRANES AB PROBLEM: Vaginally infected Sprague-Dawley (SD) rats are more susceptible to adverse pregnancy outcomes than Wistar (WIS) rats. We postulated that SD rats have enhanced hematogenous spread of Mycoplasma pulmonis to fetal tissues. METHOD OF STUDY: WIS and SD dams were infected intravenously with 10(7), 10(6), and 10(5) colony-forming units of M. pulmonis at gestation day 14. Dams and six randomly selected fetuses were cultured at days 15, 16, 17, and 18 of gestation. RESULTS: In the high-dose group, 100% of fetuses were colonized regardless of rat strain. Significantly higher numbers of M. pulmonis were isolated from placenta (low dose, P < 0.0001; medium dose, P < 0.024; high dose, P < 0.0001), amniotic fluid (low dose, P < 0.003; medium dose, P < 0.017), and fetuses (low dose, P < 0.0011) of SD rats. Spread of M. pulmonis to the amniotic fluid and fetus occurred 1 day earlier in SD rats. CONCLUSIONS: The difference in susceptibility between the two rat strains cannot be explained by hematogenous spread alone. The relative resistance to adverse pregnancy outcomes in WIS rats may be a function of a more robust innate immune system. These rat strains may represent an animal model to address host resistance factors to intrauterine infection. C1 Univ Florida, Coll Vet Med, Dept Pathobiol, Gainesville, FL 32611 USA. NICHHD, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD 20892 USA. RP Reyes, L (reprint author), Univ Florida, Coll Vet Med, Dept Pathobiol, Gainesville, FL 32611 USA. EM lreyes@vpha.health.ufl.edu FU NIAID NIH HHS [R01-AI45875-01] NR 20 TC 5 Z9 6 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 8755-8920 J9 AM J REPROD IMMUNOL JI Am. J. Reprod. Immunol. PD MAR PY 2004 VL 51 IS 3 BP 211 EP 219 DI 10.1111/j.1600-0897.2004.00144.x PG 9 WC Immunology; Reproductive Biology SC Immunology; Reproductive Biology GA 802QL UT WOS:000220177900005 PM 15209390 ER PT J AU Miller, FG Silverman, HJ AF Miller, FG Silverman, HJ TI The ethical relevance of the standard of care in the design of clinical trials SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID RESPIRATORY-DISTRESS-SYNDROME; PLACEBO-CONTROLLED TRIALS; ACUTE LUNG INJURY; TIDAL VOLUMES; DEVELOPING-COUNTRIES; PATIENT SAFETY; METAANALYSIS; DECLARATION; EQUIPOISE; HELSINKI C1 NIH, Ctr Clin, Dept Clin Bioeth, Bethesda, MD 20892 USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. RP Miller, FG (reprint author), NIH, Ctr Clin, Dept Clin Bioeth, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM fmiller@nih.gov NR 31 TC 31 Z9 32 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR 1 PY 2004 VL 169 IS 5 BP 562 EP 564 DI 10.1164/rccm.200311-1577CP PG 3 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 778PE UT WOS:000189249300008 PM 14701713 ER PT J AU McNally, M Mannon, RB Javor, ED Swanson, SJ Hale, DA Gorden, P Kirk, AD AF McNally, M Mannon, RB Javor, ED Swanson, SJ Hale, DA Gorden, P Kirk, AD TI Successful renal transplantation in a patient with congenital generalized lipodystrophy: A case report SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article ID GLOMERULONEPHRITIS; DISEASE C1 Natl Naval Med Res Inst, Dept Surg, Bethesda, MD 20889 USA. NIDDKD, NIH, US Dept HHS, Bethesda, MD 20892 USA. RP Kirk, AD (reprint author), Natl Naval Med Res Inst, Dept Surg, Bethesda, MD 20889 USA. EM AllanK@intra.niddk.nih.gov RI Kirk, Allan/B-6905-2012 NR 21 TC 10 Z9 10 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAR PY 2004 VL 4 IS 3 BP 447 EP 449 DI 10.1111/j.1600-6143.2004.00358.x PG 3 WC Surgery; Transplantation SC Surgery; Transplantation GA 774MY UT WOS:000188988100023 PM 14962001 ER PT J AU Milleron, RS Ribeiro, JMC Elnaime, D Soong, L Lanzaro, GC AF Milleron, RS Ribeiro, JMC Elnaime, D Soong, L Lanzaro, GC TI Negative effect of antibodies against maxadilan on the fitness of the sand fly vector of American visceral leishmaniasis SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID LUTZOMYIA-LONGIPALPIS DIPTERA; MOSQUITO FEEDING SUCCESS; HOST BEHAVIOR; BOOPHILUS-MICROPLUS; SANDFLIES DIPTERA; BLOOD-SUCKING; PSYCHODIDAE; SALIVA; ANOPHELES; PEPTIDE AB Lutzomyia longipalpis expresses a salivary protein called maxadilan (MAX) that functions to dilate vertebrate blood vessels and thereby to facilitate the sand fly's acquisition of blood. We hypothesized that antibodies specific for one of many MAX variants would inhibit vasodilatory function of that variant. In vitro and in vivo experiments showed that antibodies against a specific MAX variant decreased vasodilatory function. More specifically, antibodies against MAX blocked vasodilation of a constricted rabbit aorta. Additionally, a strain of Lu. longipalpis, with a nearly uniform MAX genotype, obtained a larger blood meat from naive BALB/c mice compared with mice that were either immunized with a homologous MAX genotype or sensitized to bites of flies from the same strain. Those flies taking blood from mice sensitized by sand fly bites also laid significantly fewer eggs than when they took blood from naive mice. These results have potential epidemiologic importance in light of the potential use of MAX in a vaccine or as part of a diagnostic test because they imply that a uniform MAX genotype is selected against by the vertebrate host immune response and that antigenic diversity is selected for. C1 Univ Texas, Div Pharmacol & Toxicol, Coll Pharm, Ctr Mol Cellular Toxicol, Austin, TX 78712 USA. NIAID, Med Entomol Sect, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. Univ Calif Davis, Dept Entomol, Davis, CA 95616 USA. Univ Texas, Dept Microbiol, Galveston, TX 77555 USA. Univ Texas, Dept Immunol, Med Branch, Galveston, TX 77555 USA. Univ Texas, Med Branch, Dept Pathol, Galveston, TX 77550 USA. Univ Texas, Med Branch, Collaborating Ctr Trop Dis, WHO, Galveston, TX 77550 USA. NIAID, Med Entomol Sect, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. RP Milleron, RS (reprint author), Univ Texas, Div Pharmacol & Toxicol, Coll Pharm, Ctr Mol Cellular Toxicol, 1 Univ Stn, Austin, TX 78712 USA. EM rania@uts.cc.utexas.edu; jribeiro@nih.gov; daelnaiem@ucdavis.edu; lysoong@utmb.edu; gclanzaro@ucdavis.edu OI Ribeiro, Jose/0000-0002-9107-0818 FU NIAID NIH HHS [AI-39540, T32 AI-075261] NR 48 TC 33 Z9 34 U1 0 U2 3 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD MAR PY 2004 VL 70 IS 3 BP 278 EP 285 PG 8 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 802YM UT WOS:000220198800009 PM 15031517 ER PT J AU Wu, XS Sun, JY Evers, AS Crowder, M Wu, LG AF Wu, XS Sun, JY Evers, AS Crowder, M Wu, LG TI Isoflurane inhibits transmitter release and the presynaptic action potential SO ANESTHESIOLOGY LA English DT Article ID POSTSYNAPTIC GLUTAMATE RECEPTORS; HIPPOCAMPAL PYRAMIDAL NEURONS; TERM SYNAPTIC DEPRESSION; CENTRAL-NERVOUS-SYSTEM; AUDITORY BRAIN-STEM; VOLATILE ANESTHETICS; TRAPEZOID BODY; MEDIAL NUCLEUS; THALAMOCORTICAL NEURONS; INHALATION ANESTHETICS AB Background: isoflurane inhibits the excitatory postsynaptic current (EPSC) at many synapses. Accumulated evidence suggests the involvement of a presynaptic mechanism. However, the extent of the presynaptic contribution has not been quantitatively studied. Furthermore, the mechanism underlying the presynaptic contribution remains unclear. Methods: To estimate the presynaptic contribution, the authors compared the effects of isoflurane on the presynaptic capacitance jump, which is proportional to vesicle release, and the postsynaptic glutamate receptor-mediated EPSC at a calyx-type synapse in rat brainstem. The authors determined whether isoflurane affects the waveform of the action potential recorded from nerve terminals. By studying the relation between the EPSC and the presynaptic action potential at the same synapse, the authors determined whether isoflurane inhibits the EPSC by decreasing the presynaptic action potential. Results: lsoflurane at 0.35-1-05 mm reduced the EPSC and the presynaptic capacitance jump to a similar degree without affecting the miniature EPSC (an indicator of quantal size), suggesting that isoflurane inhibits the EPSC predominantly by reducing glutamate release. isoflurane reduced the presynaptic action potential by approximately 3-8%. The EPSC was proportional to the presynaptic action potential amplitude raised to a power of 10.2. Based on this relation, inhibition of the presynaptic action potential contributed to 62-78% of isoflurane-induced inhibition of the EPSC. Conclusions: isoflurane inhibits the EPSC predominantly by inhibition of transmitter release. lsoflurane reduces the presynaptic action potential amplitude, which may contribute significantly to its inhibitory effect on the EPSC. C1 NINDS, Bethesda, MD 20892 USA. Washington Univ, Sch Med, Dept Anesthesiol, St Louis, MO 63130 USA. RP Wu, LG (reprint author), NINDS, 36 Convent Dr,Room 1C12, Bethesda, MD 20892 USA. EM wu1@ninds.nih.gov FU NIGMS NIH HHS [R01-GM59781, P01-GM47969, R01 GM059781, R01-GM65358] NR 44 TC 81 Z9 85 U1 2 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD MAR PY 2004 VL 100 IS 3 BP 663 EP 670 DI 10.1097/00000542-200403000-00029 PG 8 WC Anesthesiology SC Anesthesiology GA 778QF UT WOS:000189251700028 PM 15108983 ER PT J AU Vupputuri, S Soucie, JM McClellan, W Sandler, DP AF Vupputuri, S Soucie, JM McClellan, W Sandler, DP TI History of kidney stones as a possible risk factor for chronic kidney disease SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE kidney calculi; kidney diseases; risk factors; retrospective studies; adult; human ID STAGE RENAL-DISEASE; CHRONIC PYELONEPHRITIS; DIABETES-MELLITUS; BLOOD-PRESSURE; NEPHROLITHIASIS; INSUFFICIENCY; FAILURE; CALCULI; UROLITHIASIS; HYPERCALCIURIA AB Purpose: The incidence of treated end-stage renal disease has increased progressively in the United States over the past several decades. It has been suggested that kidney stones may be a contributing factor for a small percentage of these patients. Methods: We conducted a case-control study utilizing 548 hospital cases and 514 age, race and gender-matched community controls. The main outcome measure was diagnosis of chronic kidney disease, assessed by comprehensive chart review. History of kidney stones and other co-variables were obtained during telephone interviews. Results: This study revealed 16.8% of cases and 6.4% of controls with reported history of kidney stones. The odds ratios (adjusted for confounding variables) for chronic kidney disease (overall), diabetic nephropathy and interstitial nephritis for patients with kidney stones were 1.9 (95% CI: 1.1, 3.3), 2.5 (95% CI: 0.87, 7.0) and 3.4 (95% CI: 1.5, 7-4), respectively. After stratifying by hypertensive status this increased risk persisted only for study participants reporting no history of hypertension. Conclusion: Kidney stones may play a role in the development of chronic kidney disease. Our study suggests that the prevention of kidney stones may be a means of delaying the onset of chronic kidney disease, however, further studies are needed to make conclusive recommendations. (C) 2003 Elsevier Inc. All rights reserved. C1 NIEHS, Epidemiol Branch, Dept Hlth & Human Serv, NIH, Res Triangle Pk, NC 27709 USA. Emory Univ, Sch Med, Dept Epidemiol, Div Renal, Atlanta, GA 30322 USA. Emory Univ, Sch Med, Dept Med, Div Renal, Atlanta, GA 30322 USA. RP Vupputuri, S (reprint author), NIEHS, Epidemiol Branch, Dept Hlth & Human Serv, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM vupputu1@niehs.nih.gov OI Sandler, Dale/0000-0002-6776-0018 NR 53 TC 46 Z9 48 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD MAR PY 2004 VL 14 IS 3 BP 222 EP 228 DI 10.1016/S1047-2797(03)00126-1 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 780KK UT WOS:000189379700011 PM 15036227 ER PT J AU Oota, H Pakstis, AJ Bonne-Tamir, B Goldman, D Grigorenko, E Kajuna, SLB Karoma, NJ Kungulilo, S Lu, RB Odunsi, K Okonofua, F Zhukova, OV Kidd, JR Kidd, KK AF Oota, H Pakstis, AJ Bonne-Tamir, B Goldman, D Grigorenko, E Kajuna, SLB Karoma, NJ Kungulilo, S Lu, RB Odunsi, K Okonofua, F Zhukova, OV Kidd, JR Kidd, KK TI The evolution and population genetics of the ALDH2 locus: random genetic drift, selection, and low levels of recombination SO ANNALS OF HUMAN GENETICS LA English DT Article ID ALDEHYDE DEHYDROGENASE POLYMORPHISM; ALLELE FREQUENCY DATABASE; HUMAN LIPOPROTEIN-LIPASE; LINKAGE DISEQUILIBRIUM; ALCOHOL SENSITIVITY; HAPLOTYPE STRUCTURE; INDIAN POPULATIONS; MITOCHONDRIAL-DNA; MESSENGER-RNAS; HUMAN GENOME AB The catalytic deficiency of human aldehyde dehydrogenase 2 (ALDH2) is caused by a nucleotide substitution (G1510A; Glu487Lys) in exon 12 of the ALDH2 locus. This SNP, and four non-coding SNPs, including one in the promoter, span 40 kb of ALDH2; these and one downstream STRP have been tested in 37 worldwide populations. Only four major SNP-defined haplotypes account for almost all chromosomes in all populations. A fifth haplotype harbours the functional variant and is only found in East Asians. Though the SNPs showed virtually no historic recombination, LD values are quite variable because of varying haplotype frequencies, demonstrating that LD is a statistical abstraction and not a fundamental aspect of the genome, and is not a function solely of recombination. Among populations, different sets of tagging SNPs, sometimes not overlapping, can be required to identify the common haplotypes. Thus, solely because haplotype frequencies vary, there is no common minimum set of tagging SNPs globally applicable. The F-st values of the promoter region SNP and the functional SNP were about two S.D. above the mean for a reference distribution of 117 autosomal biallelic markers. These high F-st values may indicate selection has operated at these or very tightly linked sites. C1 Yale Univ, Sch Med, Dept Genet, New Haven, CT 06520 USA. Tel Aviv Univ, Sackler Sch Med, Dept Human Genet, IL-69978 Tel Aviv, Israel. NIAAA, Neurogenet Lab, Rockville, MD 20852 USA. Yale Univ, Dept Psychol, New Haven, CT 06520 USA. Hubert Kairuki Mem Univ, Dar Es Salaam, Tanzania. Muhimbili Univ, Coll Hlth Sci, Dar Es Salaam, Tanzania. Tri Serv Gen Hosp, Dept Psychiat, Natl Def Med Ctr, Taipei, Taiwan. Roswell Pk Canc Inst, Dept Gynecol Oncol, Buffalo, NY 14263 USA. Univ Benin, Fac Med, Dept Obstet & Gynecol, Benin, Nigeria. RAS, NI Vavilov Inst Gen Genet, Moscow, Russia. RP Kidd, KK (reprint author), Yale Univ, Sch Med, Dept Genet, SHM I-351,333 Cedar St,POB 208005, New Haven, CT 06520 USA. EM kidd@biomed.med.yale.edu RI Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 FU NIAAA NIH HHS [AA09379]; NIGMS NIH HHS [GM57672] NR 58 TC 73 Z9 76 U1 2 U2 15 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0003-4800 J9 ANN HUM GENET JI Ann. Hum. Genet. PD MAR PY 2004 VL 68 BP 93 EP 109 DI 10.1046/j.1529-8817.2003.00060.x PN 2 PG 17 WC Genetics & Heredity SC Genetics & Heredity GA 802ZD UT WOS:000220200500002 PM 15008789 ER PT J AU Murase, N Duque, J Mazzocchio, R Cohen, LG AF Murase, N Duque, J Mazzocchio, R Cohen, LG TI Influence of interhemispheric interactions on motor function in chronic stroke SO ANNALS OF NEUROLOGY LA English DT Article ID TRANSCRANIAL MAGNETIC STIMULATION; FOLLOW-UP; CORTICOSPINAL EXCITABILITY; SENSORIMOTOR CORTEX; EVOKED-POTENTIALS; REACTION-TIME; RECOVERY; ACTIVATION; REORGANIZATION; INHIBITION AB In patients with chronic stroke, the primary motor cortex of the intact hemisphere (M1(intact) (hemisphere)) may influence functional recovery, possibly through transcallosal effects exerted over M1 in the lesioned hemisphere (M1(lesioned) (hemisphere)). Here, we studied interhemispheric inhibition (IHI) between M1(intact) (hemisphere) and M1(lesioned hemisphere) in the process of generation of a voluntary movement by the paretic hand in patients with chronic subcortical stroke and in healthy volunteers. IHI was evaluated in both hands preceding the onset of unilateral voluntary index finger movements (paretic hand in patients, right hand in controls) in a simple reaction time paradigm. IHI at rest and shortly after the Go signal were comparable in patients and controls. Closer to movement onset, IHI targeting the moving index finger turned into facilitation in controls but remained deep in patients, a finding that correlated with poor motor performance. These results document an abnormally high interhemispheric inhibitory drive from M1(intact) (hemisphere) to M1(lesioned hemisphere) in the process of generation of a voluntary movement by the paretic hand. It is conceivable that this abnormality could adversely influence motor recovery in some patients with subcortical stroke, an interpretation consistent with models of interhemispheric competition in motor and sensory systems. C1 NINDS, Human Cortical Physiol Sect, NIH, Bethesda, MD 20817 USA. Univ Tokushima, Dept Neurol, Fac Med, Tokushima 770, Japan. Univ Louvain, Neurophysiol Lab, Brussels, Belgium. Univ Siena, Dept Neurol Sci, Clin Neurophysiol Sect, I-53100 Siena, Italy. RP Cohen, LG (reprint author), NINDS, Human Cortical Physiol Sect, NIH, Bethesda, MD 20817 USA. EM cohenl@ninds.nih.gov RI Mazzocchio, Riccardo/H-4223-2012 OI Mazzocchio, Riccardo/0000-0002-0628-2868 NR 44 TC 636 Z9 660 U1 2 U2 33 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD MAR PY 2004 VL 55 IS 3 BP 400 EP 409 DI 10.1002/ana.10848 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 779BM UT WOS:000189275800012 PM 14991818 ER PT J AU Vermeulen, R Li, GL Lan, Q Dosemeci, M Rappaport, SM Xu, BH Smith, MT Zhang, LP Hayes, RB Linet, M Mu, RD Wang, L Xu, JN Yin, SN Rothman, N AF Vermeulen, R Li, GL Lan, Q Dosemeci, M Rappaport, SM Xu, BH Smith, MT Zhang, LP Hayes, RB Linet, M Mu, RD Wang, L Xu, JN Yin, SN Rothman, N TI Detailed exposure assessment for a molecular epidemiology study of benzene in two shoe factories in China SO ANNALS OF OCCUPATIONAL HYGIENE LA English DT Article DE benzene; China; exposure assessment; glues; molecular epidemiology; principal component analysis; shoe manufacturing; toluene ID RISK ASSESSMENT; OCCUPATIONAL EXPOSURE; WORKERS; LEUKEMIA; MORTALITY; COHORT AB Objectives: We carried out a detailed exposure assessment of benzene and toluene in two shoe factories in Tianjin, China. Our goal was to identify workers with a broad range of benzene exposures, for an epidemiologic study relating exposure to early biologic effects. Methods: A comprehensive exposure survey program was initiated. Over a period of 16 months, 2783 personal solvent exposure samples were collected in two workplaces from 250 workers. Mixed-effects models were used to identify factors affecting exposure. Principal component analyses (PCA) and subsequent regression analyses on the scores of the identified principal components were used to relate potential co-exposures to various exposure sources present in the workplace. Results: The mean benzene exposure level was 21.86 p.p.m. (10th-90th percentiles 5.23-50.63 p.p.m.) in the smaller shoe factory (factory A) and 3.46 p.p.m. (10th-90th percentiles 0.20-7.00 p.p.m.) in the larger shoe factory (factory B). Within-factory exposure levels differed among job titles and were higher for subjects directly involved in handling glues. In contrast, mean toluene levels were relatively similar in the two factories (factory A, 9.52 p.p.m.; factory B,15.88 p.p.m.). A seasonal trend was identified for both benzene and toluene in factory B. This could be explained in part by changes in air movement and ventilation patterns occurring during the year. A seasonal trend was not present in the smaller shoe factory, where general ventilation was absent. Supplemental analysis showed that exposure levels to other hydrocarbons were low (less than or equal to5 p.p.m.), less than 5% of their respective ACGIH threshold limit values, and generally comparable in the two factories. PCA showed that co-exposures in factory B could largely be explained by glue sources that were used in distinct areas in the workplace. Conclusions: We demonstrated the occurrence of a broad range of benzene exposure levels in two shoe manufacturing factories in Tianjin, China. Benzene and toluene exposures were determined in part by the degree of contact with glues, the benzene and toluene content of each glue, air movement and ventilation patterns. The availability of long-term monthly personal monitoring data provides an excellent opportunity to estimate individual exposures at different times during the 1 yr period of observation. C1 NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA. Natl Inst Occupat Hlth & Poison Control, China CDC, Beijing, Peoples R China. Univ N Carolina, Chapel Hill, NC USA. Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Rockville, MD USA. Tianjin Ctr Hlth & Dis Prevent, Tianjin, Peoples R China. RP Vermeulen, R (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, 6120 Execut Blvd, Bethesda, MD 20892 USA. EM vermeulr@mail.nih.gov RI Vermeulen, Roel/F-8037-2011 OI Vermeulen, Roel/0000-0003-4082-8163 FU NIEHS NIH HHS [P30 ES01896, P42 ES04705, P42ES05948, R01 ES06721] NR 25 TC 45 Z9 48 U1 1 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0003-4878 J9 ANN OCCUP HYG JI Ann. Occup. Hyg. PD MAR PY 2004 VL 48 IS 2 BP 105 EP 116 DI 10.1093/annhyg/meh005 PG 12 WC Public, Environmental & Occupational Health; Toxicology SC Public, Environmental & Occupational Health; Toxicology GA 807HI UT WOS:000220492200002 PM 14990432 ER PT J AU Feldman, ED Pingpank, JF Alexander, HR AF Feldman, ED Pingpank, JF Alexander, HR TI Regional treatment options for patients with ocular melanoma metastatic to the liver SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article DE regional therapy; liver metastases; chemoembolization; isolation perfusion; intra-arterial chemotherapy; immunotherapy ID ISOLATED HEPATIC PERFUSION; TUMOR-NECROSIS-FACTOR; UVEAL MELANOMA; CHOROIDAL MELANOMA; PHASE-I; INTRAARTERIAL CHEMOTHERAPY; HEPATOCELLULAR-CARCINOMA; POLYVINYL SPONGE; VENOUS ISOLATION; SURVIVAL AB Ocular melanoma is the most common primary ocular malignancy and has a significant predilection for metastasis to the liver. More than 40% of patients have hepatic metastases present at initial diagnosis, and the liver becomes involved in up to 95% of individuals who develop metastatic disease. The median survival of patients after diagnosis of liver metastasis ranges from 2 to 7 months. Metastatic disease localized to the liver has proven to be resistant to most available chemotherapy and immunotherapy regimens. Recognition of the grave prognosis associated with liver metastasis from ocular melanoma has led to the evaluation of new regional treatment modalities primarily designed to control tumor progression in the liver, including hepatic arterial chemotherapy, hepatic artery chemoembolization, regional immunotherapy, isolated hepatic perfusion, and percutaneous hepatic perfusion. This article reviews the efficacy, outcomes, and morbidities of the multiple locoregional therapies available today. C1 NCI, Surg Metab Sect, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Alexander, HR (reprint author), NCI, Surg Metab Sect, Surg Branch, NIH, Bldg 10,Room 2B07, Bethesda, MD 20892 USA. EM richard_alexander@nih.gov NR 56 TC 50 Z9 51 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD MAR PY 2004 VL 11 IS 3 BP 290 EP 297 DI 10.1245/ASO.2004.07.004 PG 8 WC Oncology; Surgery SC Oncology; Surgery GA 780KX UT WOS:000189380800012 PM 14993024 ER PT J AU Holland, DT DiFrancesco, R Stone, J Hamzeh, F Connor, JD Morse, GD AF Holland, DT DiFrancesco, R Stone, J Hamzeh, F Connor, JD Morse, GD TI Quality assurance program for clinical measurement of antiretrovirals: AIDS Clinical Trials Group proficiency testing program for pediatric and adult pharmacology laboratories SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; TANDEM MASS-SPECTROMETRY; PROTEASE INHIBITORS; HIV-1-INFECTED PATIENTS; TREATMENT FAILURE; PLASMA-LEVELS; THERAPY; ZIDOVUDINE; INDINAVIR; LAMIVUDINE AB Clinical trials designed to compare antiretroviral regimens, investigate therapeutic drug monitoring, or measure pharmacometrics often include protease inhibitors (PIs), normucleoside reverse transcriptase inhibitors (NNRTIs), and nucleoside reverse transcriptase inhibitors, requiring the measurement of these antiretrovirals in plasma. Within the adult and pediatric AIDS Clinical Trials Group (ACTG), a network of Pharmacology Support Laboratories (PSLs) is a component of the group laboratory infrastructure and conducts these types of pharmacologic assays. The adult ACTG has developed a comprehensive quality assurance program for the conduct of clinical pharmacology protocols, one component of which is the antiretroviral proficiency testing (PT) program that has been implemented between the adult and pediatric pharmacology laboratories of the ACTG. PT testing samples were prepared and distributed in July 2001, February 2002, and July 2002. High, medium, and low concentrations of PIs (indinavir, saquinavir, amprenavir, lopinavir, ritonavir, and nelfinavir) and NNRTIs (nevirapine and efavirenz) were added to drug-free EDTA plasma and distributed, on dry ice, to eight ACTG PSLs. One testing laboratory used liquid chromatography-tandem mass spectrometry, and seven used high-performance liquid chromatography-UV analysis. A result was considered acceptable if it was within 20% deviation of the assigned concentration. For all concentrations of PIs evaluated, 96% of samples tested (430 of 448 measurements) met the acceptance criteria. For both NNRTIs, 100% of samples tested (140 of 140 measurements) met the acceptance criteria. In conclusion, the PT program results presented demonstrate excellent interlaboratory agreement for all antiretrovirals tested and provide support for the merger of plasma concentration data among laboratories for large clinical trials. C1 NIAID, Adult & Pediat AIDS Clin Trials Grp, Pharmacol Lab Comm, Pedia AIDS Clin Trials Grp,Div AIDS,NIH, Bethesda, MD 20892 USA. RP Morse, GD (reprint author), SUNY Buffalo, Sch Pharm & Pharmaceut Sci, AACTG Pharmacol Support Lab, Room 317,Hochstetter Hall, Buffalo, NY 14260 USA. EM emorse@acsu.buffalo.edu FU NCRR NIH HHS [S1RR14572] NR 17 TC 53 Z9 53 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD MAR PY 2004 VL 48 IS 3 BP 824 EP 831 DI 10.1128/AAC.48.3.824-831.2004 PG 8 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 780BQ UT WOS:000189351700018 PM 14982771 ER PT J AU Zhang, MY Shu, Y Sidorov, I Dimitrov, DS AF Zhang, MY Shu, Y Sidorov, I Dimitrov, DS TI Identification of a novel CD4i human monoclonal antibody Fab that neutralizes HIV-1 primary isolates from different clades SO ANTIVIRAL RESEARCH LA English DT Article DE HIV; antibody; phage display; gp120; inhibitors; vaccines ID IMMUNODEFICIENCY-VIRUS TYPE-1; BINDING-SITE; GP120; GLYCOPROTEIN; EPITOPE; 2G12; GP41; 2F5 AB A new human monoclonal antibody (hmAb), designated m 16, was selected by sequential antigen panning (SAP) of a human phage display library against recombinant soluble HIV-1 envelope glycoproteins (Envs) (gp140s) and their complexes with soluble CD4. It bound with high (nM) affinity to gp120 and gp140; the binding was further enhanced by interactions of the Envs with CD4. m16 inhibited cell fusion mediated by the Envs of 9 HIV-1 isolates from clades A, B, E and G with potency on average comparable to that of the broadly neutralizing human monoclonal antibody Fab X5. The identification of a new hmAb with broad neutralizing activity that exhibits differential inhibitory profile suggests a potential for its use as a component of anti-HIV-1 treatments. Published by Elsevier B.V. C1 NCI, Human Immunovirol & Computat Biol Grp, LECB, CCR,NIH, Frederick, MD 21702 USA. NCI, BRP, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Dimitrov, DS (reprint author), NCI, Human Immunovirol & Computat Biol Grp, LECB, CCR,NIH, Frederick, MD 21702 USA. EM dimitrov@ncifcrf.gov OI Sidorov, Igor/0000-0001-6519-4983 FU NCI NIH HHS [N01-CO-12400] NR 20 TC 18 Z9 20 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD MAR PY 2004 VL 61 IS 3 BP 161 EP 164 DI 10.1016/j.antiviral.2003.09.009 PG 4 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA 776RP UT WOS:000189131000003 PM 15168796 ER PT J AU Lee, DW Jang, HJ Choe, EA Kim, BC Lee, SJ Kim, SB Hong, YH Pyun, YR AF Lee, DW Jang, HJ Choe, EA Kim, BC Lee, SJ Kim, SB Hong, YH Pyun, YR TI Characterization of a thermostable L-arabinose (D-galactose) isomerase from the hyperthermophilic eubacterium Thermotoga maritima SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID ESCHERICHIA-COLI; D-TAGATOSE; GLUCOSE-ISOMERASE; PURIFICATION; CLONING; BIOCONVERSION; EXPRESSION; SEQUENCE; ENZYME; NEAPOLITANA AB The araA gene encoding L-arabinose isomerase (AI) from the hyperthermophilic bacterium Thermotoga maritima was cloned and overexpressed in Escherichia coli as a fusion protein containing a C-terminal hexahistidine sequence. This gene encodes a 497-amino-acid protein with a calculated molecular weight of 56,658. The recombinant enzyme was purified to homogeneity by heat precipitation followed by Ni2+ affinity chromatography. The native enzyme was estimated by gel filtration chromatography to be a homotetramer with a molecular mass of 232 kDa. The purified recombinant enzyme had an isoelectric point of 5.7 and exhibited maximal activity at 90degreesC and pH 7.5 under the assay conditions used. Its apparent K-m values for L-arabinose and D-galactose were 31 and 60 mM, respectively; the apparent V.., values (at 90degreesC) were 41.3 U/mg (L-arabinose) and 8.9 U/mg (D-galactose), and the catalytic efficiencies (k(cat)/K-m) of the enzyme were 74.8 mM(-1) (.)min(-1) (L-arabinose) and 8.5 mM(-1) (.) min(-1) (D-galactose). Although the T. maritima AI exhibited high levels of amino acid sequence similarity (>70%) to other heat-labile mesophilic AIs, it had greater thermostability and higher catalytic efficiency than its mesophilic counterparts at elevated temperatures. In addition, it was more thermostable in the presence of Mn2+ and/or Co2+ than in the absence of these ions. The enzyme carried out the isomerization Of D-galactose to D-tagatose with a conversion yield of 56% for 6 h at 80degreesC. C1 Yonsei Univ, Coll Engn, Dept Biotechnol & Bioprod Res Ctr, Seoul 120749, South Korea. NIA, Diabet Sect, Clin Invest Lab, NIH, Baltimore, MD 21224 USA. Univ Massachusetts, Dept Microbiol, Amherst, MA 01003 USA. RP Pyun, YR (reprint author), Yonsei Univ, Coll Engn, Dept Biotechnol & Bioprod Res Ctr, Shinchon Dong 134, Seoul 120749, South Korea. EM yrpyun@yonsei.ac.kr RI jang, hyeung jin/C-8022-2013 NR 32 TC 78 Z9 88 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD MAR PY 2004 VL 70 IS 3 BP 1397 EP 1404 DI 10.1128/AEM.70.3.1397-1404.2004 PG 8 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 802HO UT WOS:000220154800019 PM 15006759 ER PT J AU Roberts, KP Lamb, ME Sternberg, KJ AF Roberts, KP Lamb, ME Sternberg, KJ TI The effects of rapport-building style on children's reports of a staged event SO APPLIED COGNITIVE PSYCHOLOGY LA English DT Article; Proceedings Paper CT Biennial Meeting of the American-Psychology-Law-Society CY MAR, 2000 CL NEW ORLEANS, LA SP Amer Psychol Law Soc ID ABUSE VICTIMS; SEXUAL ABUSE; INVESTIGATIVE INTERVIEWS; FORENSIC INTERVIEWS/; INFORMATION; MEMORIES; AGE AB Three- to nine-year-old children (n = 144) interacted with a photographer and were interviewed about the event either a week or a month later. The informativeness and accuracy of information provided following either open-ended or direct rapport building were compared. Children in the open-ended rapport-building condition provided more accurate reports than children in the direct rapport-building condition after both short and long delays. Open-ended rapport-building led the three- to four-year-olds to report more errors in response to the first recall question about the event, but they went on to provide more accurate reports in the rest of the interview than counterparts in the direct rapport-building condition. These results suggest that forensic interviewers should attempt to establish rapport with children using an open-ended style. Published in 2004 by John Wiley Sons, Ltd. C1 NICHHD, Sect Social & Emot Dev, Rockledge Ctr 1, Bethesda, MD 20892 USA. RP Lamb, ME (reprint author), NICHHD, Sect Social & Emot Dev, Rockledge Ctr 1, Suite 8048,6705 Rockledge Dr, Bethesda, MD 20892 USA. EM Michael_Lamb@nih.gov NR 21 TC 52 Z9 52 U1 3 U2 13 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0888-4080 J9 APPL COGNITIVE PSYCH JI Appl. Cogn. Psychol. PD MAR PY 2004 VL 18 IS 2 BP 189 EP 202 DI 10.1002/acp.957 PG 14 WC Psychology, Experimental SC Psychology GA 808BW UT WOS:000220545600005 ER PT J AU Stadtman, ER AF Stadtman, ER TI Cyclic oxidation and reduction of methionine residues of proteins in antioxidant defense and cellular regulation SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article; Proceedings Paper CT Annual Meeting of the Oxygen Club of California (OCC) CY MAR 10-13, 2004 CL SANTA BARBARA, CALIFORNIA SP Linus Pauling Inst, Soc Free Rad Res Int ID ALKYL HYDROPEROXIDE REDUCTASE; S-OXIDASE ACTIVITY; SULFOXIDE REDUCTASE; ESCHERICHIA-COLI; SALMONELLA-TYPHIMURIUM; SUBSTRATE STEREOSPECIFICITY; KIDNEY MICROSOMES; RABBIT LIVER; DAMAGE; MECHANISM C1 NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Stadtman, ER (reprint author), NHLBI, Biochem Lab, NIH, Bldg 50,Room 2140,50 S Dr,MSC-8012, Bethesda, MD 20892 USA. EM erstadtman@nih.gov NR 53 TC 43 Z9 44 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD MAR 1 PY 2004 VL 423 IS 1 BP 2 EP 5 DI 10.1016/j.abb.2003.10.001 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 774FT UT WOS:000188969700002 PM 14989257 ER PT J AU Polidori, MC Mecocci, P Levine, M Frei, B AF Polidori, MC Mecocci, P Levine, M Frei, B TI Short-term and long-term vitamin C supplementation in humans dose-dependently increases the resistance of plasma to ex vivo lipid peroxidation SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article; Proceedings Paper CT Annual Meeting of the Oxygen Club of California (OCC) CY MAR 10-13, 2004 CL SANTA BARBARA, CALIFORNIA SP Linus Pauling Inst, Soc Free Rad Res Int DE vitamin C; oxidative stress; supplementation; lipid peroxidation ID HUMAN-BLOOD-PLASMA; LOW-DENSITY-LIPOPROTEIN; RECOMMENDED DIETARY ALLOWANCE; STRESS IN-VIVO; ASCORBIC-ACID; BIOMARKER F-2-ISOPROSTANES; ANTIOXIDANT; DISEASE; DAMAGE; PROOXIDANT AB To assess the effects of short-term and long-term vitamin C supplementation in humans on plasma antioxidant status and resistance to oxidative stress, plasma was obtained from 20 individuals before and 2 h after oral administration of 2 g of vitamin C, or from eight subjects enrolled in a vitamin C depletion-repletion study using increasing daily doses of vitamin C from 30 to 2500 mg. Plasma concentrations of ascorbate, but not other physiological antioxidants, increased significantly after short-term supplementation, and increased progressively in the long-term study with increasing vitamin C doses of up to 1000 mg/day. Upon incubation of plasma with a free radical initiator, ascorbate concentrations were positively correlated with the lag phase preceding detectable lipid peroxidation. We conclude that vitamin C supplementation in humans dose-dependently increases plasma ascorbate concentrations and, thus, the resistance of plasma to-lipid peroxidation ex vivo. Plasma and body saturation with vitamin C in humans appears desirable to maximize antioxidant protection and lower risk of oxidative damage. (C) 2003 Elsevier Inc. All rights reserved. C1 Oregon State Univ, Linus Pauling Inst, Corvallis, OR 97331 USA. Univ Dusseldorf, Inst Biochem & Mol Biol 1, Dusseldorf, Germany. Perugia Univ Hosp, Inst Gerontol & Geriatr, Perugia, Italy. NIDDK, Mol & Clin Nutr Sect, Digest Dis Branch, NIH, Bethesda, MD USA. RP Frei, B (reprint author), Oregon State Univ, Linus Pauling Inst, Corvallis, OR 97331 USA. EM balz.frei@oregonstate.edu FU NCCIH NIH HHS [AT00066]; NHLBI NIH HHS [HL60886] NR 27 TC 40 Z9 43 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD MAR 1 PY 2004 VL 423 IS 1 BP 109 EP 115 DI 10.1016/j.abb.2003.12.019 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 774FT UT WOS:000188969700016 PM 14871474 ER PT J AU Uhl, GR Grow, RW AF Uhl, GR Grow, RW TI The burden of complex genetics in brain disorders SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID POPULATION-BASED TWIN; GENERALIZED ANXIETY DISORDER; ALZHEIMERS-DISEASE; MULTIPLE-SCLEROSIS; PARKINSONS-DISEASE; ALCOHOL DEPENDENCE; ABUSE-VULNERABILITY; MAJOR DEPRESSION; SUBSTANCE-ABUSE; FOLLOW-UP AB Background: Few data estimate the impact of complex genetics in neuropsychiatric illness, making it likely that this impact could be underappreciated. Objective: To provide estimates of the impact of complex genetics in neuropsychiatric disorders in the United States, based on estimates of disease costs to US society, disease heritability, and mendelian contributions to disease. Data Sources, Study Selection, and Data Extraction: Costs were estimated from literature sources and Lewin-National Foundation for Brain Research estimates updated for population growth and consumer price index inflation. Heritability estimates came from available twin data. Estimates of mendelian contributions came from the Online Mendelian Inheritance in Man database and our perspectives. Conclusions: Brain and nervous system disorders may cost the United States as much as $1.2 trillion annually, and affect many millions of Americans each year. Twin data suggest that more than 40% of the societal burden of brain disorders is likely to be genetically mediated. Most of this disease burden arises from complex multigene genetics as well as from environmental influences. The large sizes of these complex genetic burdens should encourage careful molecular and clinical work to link disease-vulnerability allelic variants with the pathogenesis, nosologic characteristics, prevention, diagnostics, and therapeutics of brain disorders. C1 NIDA, Mol Neurobiol Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21218 USA. RP Uhl, GR (reprint author), NIDA, Mol Neurobiol Branch, Intramural Res Program, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM guhl@intra.nida.nih.gov NR 75 TC 95 Z9 98 U1 1 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD MAR PY 2004 VL 61 IS 3 BP 223 EP 229 DI 10.1001/archpsyc.61.3.223 PG 7 WC Psychiatry SC Psychiatry GA 800YY UT WOS:000220064800002 PM 14993109 ER PT J AU Carmody, AB Otto, M AF Carmody, AB Otto, M TI Specificity grouping of the accessory gene regulator quorum-sensing system of Staphylococcus epidermidis is linked to infection SO ARCHIVES OF MICROBIOLOGY LA English DT Article DE Staphylococcus epidermidis; infection; quorum-sensing ID AGR SYSTEM; PHEROMONE; AUREUS; PEPTIDE; INHIBITION AB Staphylococcus epidermidis represents the most frequent pathogen involved in nosocomial infections and infections of indwelling medical devices. The strain-to-strain variation of the gene encoding the quorum-sensing pheromone of S. epidermidis as well as the correlation between specificity groups and origin from infection were determined. The pro-pheromone gene was highly conserved and showed infrequent, non-synonymous, single-nucleotide polymorphisms that led to conservative amino acid exchanges only. Importantly, one specificity group was significantly more frequent among strains isolated from infection. The finding that quorum-sensing specificity groups are linked to infection demonstrates the relevance of quorum-sensing for virulence in this critical human pathogen and contributes to the scientific basis needed for the development of quorum-sensing-targeting drugs. 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. EM motto@niaid.nih.gov OI Otto, Michael/0000-0002-2222-4115 NR 15 TC 14 Z9 14 U1 2 U2 4 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0302-8933 J9 ARCH MICROBIOL JI Arch. Microbiol. PD MAR PY 2004 VL 181 IS 3 BP 250 EP 253 DI 10.1007/s00203-003-0644-2 PG 4 WC Microbiology SC Microbiology GA 777UV UT WOS:000189198000009 PM 14714104 ER PT J AU Berman, JJ AF Berman, JJ TI Zero-check - A zero-knowledge protocol for reconciling patient identities across institutions SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID CONFIDENTIALITY AB Context.-Large, multi-institutional studies often involve merging data records that have been de-identified to protect patient privacy. Unless patient identities can be reconciled across institutions, individuals with records held in different institutions will be falsely "counted" as multiple persons when databases are merged. Objective.-The purpose of this article is to describe a protocol that can reconcile individuals with records in multiple institutions. Design.-Institution A and Institution B each create a random character string and send it to the other institution. Each institution receives the random string from the other institution and sums it with their own random string, producing a random string common to both institutions (RandA+B). Each institution takes a unique patient identifier and sums it with RandA+B. The product is a random character string that is identical across institutions when the patient is identical in both institutions. A comparison protocol can be implemented as a zero-knowledge transaction, ensuring that neither institution obtains any knowledge of its own patient or of the patient compared at another institution. Results.-The protocol can be executed at high computational speed. No encryption algorithm or 1-way hash algorithm is employed, and there is no need to protect the protocol from discovery. Conclusion.-A zero-knowledge protocol for reconciling patients across institutions is described. This protocol is one of many computational tools that permit pathologists to safely share clinical and research data. C1 NCI, Canc Diag Program, NIH, Rockville, MD 20892 USA. RP Berman, JJ (reprint author), NCI, Canc Diag Program, NIH, EPN-6028,6130 Execut Blvd, Rockville, MD 20892 USA. EM bermanj@mail.nih.gov NR 12 TC 19 Z9 19 U1 0 U2 0 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD MAR PY 2004 VL 128 IS 3 BP 344 EP 346 PG 3 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 801OL UT WOS:000220105100018 PM 14987147 ER PT J AU Berman, JJ AF Berman, JJ TI Pathology abbreviated - A long review of short terms SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Review AB Context.-Abbreviations are used frequently in pathology reports and medical records. Efforts to identify and organize free-text concepts must correctly interpret medical abbreviations. During the past decade, the author has collected more than 12 000 medical abbreviations, concentrating on terms used or interpreted by pathologists. Objective.-The purpose of the study is to provide readers with a listing of abbreviations. The listing of abbreviations is reviewed for the purpose of determining the variety of ways that long forms are shortened. Design.-Abbreviations fell into different classes. These classes seemed amenable to distinct algorithmic approaches to their correct expansions. A discussion of these abbreviation classes was included to assist informaticians who are searching for ways to write software that expands abbreviations found in medical text. Classes were separated by the algorithmic approaches that could be used to map abbreviations to their correct expansions. A Perl implementation was developed to automatically match expansions with Unified Medical Language System concepts. Measurements.-The abbreviation list contained 12 097 terms; 5772 abbreviations had unique expansions. There were 6325 polysemous abbreviation/expansion pairs. The expansions of 8599 abbreviations mapped to Unified Medical Language System concepts. Three hundred twenty-four abbreviations could be confused with unabbreviated words. Two hundred thirteen abbreviations had different expansions depending on whether the American or the British spellings were used. Nine hundred seventy abbreviations ended in the letter "s." Results.-There were 6 nonexclusive groups of abbreviations classed by expansion algorithm, as follows: (1) ephemeral; (2) hyponymous; (3) monosemous; (4) polysemous; (5) masqueraders of common words; and (6) fatal (abbreviations whose incorrect expansions could easily result in clinical errors). Conclusion.-Collecting and classifying abbreviations creates a logical approach to the development of class-specific algorithms designed to expand abbreviations. A large listing of medical abbreviations is placed into the public domain. The most current version is available at http://www.pathologyinformatics.org/downloads/abbtwo.htm. C1 NCI, Canc Diag Program, NIH, Rockville, MD 20892 USA. RP Berman, JJ (reprint author), NCI, Canc Diag Program, NIH, EPN-6028,6130 Execut Blvd, Rockville, MD 20892 USA. EM bermanj@mail.nih.gov NR 5 TC 9 Z9 9 U1 1 U2 1 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD MAR PY 2004 VL 128 IS 3 BP 347 EP 352 PG 6 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 801OL UT WOS:000220105100019 PM 14987146 ER PT J AU Wormser, U Sintov, A Brodsky, B Casillas, RP Nyska, A AF Wormser, U Sintov, A Brodsky, B Casillas, RP Nyska, A TI Protective effect of topical iodine containing anti-inflammatory drugs against sulfur mustard-induced skin lesions SO ARCHIVES OF TOXICOLOGY LA English DT Article DE sulfur mustard; mustard gas; skin toxicity; dermatotoxicity; iodine; anti-inflammatory agents ID EAR VESICANT MODEL; CHEMICAL WARFARE AGENT; NITRIC-OXIDE SYNTHASE; HAIRLESS GUINEA-PIGS; ORGAN-CULTURE; ARGININE ANALOGS; RABBIT SKIN; HISTOPATHOLOGIC FEATURES; INFLAMMATORY MEDIATORS; CLOBETASOL PROPIONATE AB Previous studies have shown the antidotal efficacy of topical iodine at 15 and 30 min post-exposure to sulfur mustard (SM). Here we demonstrate efficacy at longer intervals (20, 30, 45, and 60 min, respectively, for data) using an improved topical povidone-iodine preparation termed N66, which contains steroidal and non-steroidal anti-inflammatory agents. In the mouse, N66 reduced severity of ear edema by 43, 47, 44, and 36%; ear epidermal ulceration by 74, 58, 45, and 58%; and epidermal necrosis by 54, 34, 26, and 31% at the respective time points. A similar effect was observed with encrustation. The healing marker, grade of acanthotic area, showed dramatic increases of 39.6-, 25.3-, 20.9-, and 22-fold. Severity of the dermal parameters, acute inflammation and dermal necrosis, was reduced by 63, 34, 34, and 38% and 80, 54, 54, and 59%, respectively. In guinea pig skin, topical treatment with N66 45 min post-exposure reduced the SM-induced ulceration area by 75%. The histological parameters subepidermal microblister formation, epidermal ulceration, epidermal necrosis, and encrustation were reduced by 63, 61, 41, and 41%, respectively. The healing marker, grade of acanthotic area, was elevated by 73%. N66 induced a statistically significant reduction in two dermal markers for tissue damage: acute inflammation (33%) and dermal necrosis (48%). Reduced skin damage was also observed in areas adjacent the treated sites. The pharmacologically active components of N66 showed additive effect. These findings suggest that the povidone-iodine preparation combined with anti-inflammatory agents functions as a potent antidote against skin lesions induced by SM at relatively long intervals between exposure and treatment. C1 Hebrew Univ Jerusalem, Inst Life Sci, IL-91904 Jerusalem, Israel. Hebrew Univ Jerusalem, Davis R Bloom Ctr Pharm, IL-91904 Jerusalem, Israel. Hebrew Univ Jerusalem, Fac Med, Dept Pharmacol, Sch Pharm, IL-91172 Jerusalem, Israel. Ben Gurion Univ Negev, Inst Appl Res, IL-84105 Beer Sheva, Israel. Battelle Mem Inst, Med Res & Evaluat Facil, Columbus, OH 43201 USA. NIEHS, Lab Expt Pathol, Res Triangle Pk, NC 27713 USA. RP Wormser, U (reprint author), Hebrew Univ Jerusalem, Inst Life Sci, Berman Bldg, IL-91904 Jerusalem, Israel. EM wormser@cc.huji.ac.il NR 56 TC 15 Z9 15 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0340-5761 J9 ARCH TOXICOL JI Arch. Toxicol. PD MAR PY 2004 VL 78 IS 3 BP 156 EP 166 DI 10.1007/s00204-003-0523-2 PG 11 WC Toxicology SC Toxicology GA 804KX UT WOS:000220298700005 PM 14618300 ER PT J AU Brewer, HB AF Brewer, HB TI High-density lipoproteins: A new potential therapeutic target for the prevention of cardiovascular disease SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Editorial Material ID ESTER TRANSFER PROTEIN; APOLIPOPROTEIN-A-I; CORONARY-HEART-DISEASE; CELLULAR CHOLESTEROL EFFLUX; TRANSGENIC MICE; ATHEROSCLEROTIC LESIONS; ABCA1 TRANSPORTER; CONTROLLED-TRIAL; GENE-EXPRESSION; X-RECEPTOR C1 NHLBI, Mol Dis Branch, NIH, Bethesda, MD 20892 USA. RP Brewer, HB (reprint author), NHLBI, Mol Dis Branch, NIH, Bldg 10,Room 7N115, Bethesda, MD 20892 USA. EM bryan@mdb.nhlbi.nih.gov NR 66 TC 93 Z9 100 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD MAR PY 2004 VL 24 IS 3 BP 387 EP 391 DI 10.1161/01.ATV.0000121505.88326.d2 PG 5 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 800UI UT WOS:000220052800001 PM 15003970 ER PT J AU Mosca, L Appel, LJ Benjamin, EJ Berra, K Chandra-Strobos, N Fabunmi, RP Grady, D Haan, CK Hayes, SN Judelson, DR Keenan, NL McBride, P Oparil, S Ouyang, P Oz, MC Mendelsohn, ME Pasternak, RC Pinn, VW Robertson, RM Schenck-Gustafsson, K Sila, CA Smith, SC Sopko, G Taylor, AL Walsh, BW Wenger, NK Williams, CL AF Mosca, L Appel, LJ Benjamin, EJ Berra, K Chandra-Strobos, N Fabunmi, RP Grady, D Haan, CK Hayes, SN Judelson, DR Keenan, NL McBride, P Oparil, S Ouyang, P Oz, MC Mendelsohn, ME Pasternak, RC Pinn, VW Robertson, RM Schenck-Gustafsson, K Sila, CA Smith, SC Sopko, G Taylor, AL Walsh, BW Wenger, NK Williams, CL CA Expert Panel Writing Grp TI Evidence-based guidelines for cardiovascular disease prevention in women SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Review ID CORONARY-HEART-DISEASE; ACUTE MYOCARDIAL-INFARCTION; RANDOMIZED CONTROLLED-TRIAL; HORMONE REPLACEMENT THERAPY; HIGH-RISK PATIENTS; NONRHEUMATIC ATRIAL-FIBRILLATION; CONVERTING-ENZYME-INHIBITOR; FACTOR INTERVENTION TRIAL; PLACEBO-CONTROLLED TRIAL; TIME PHYSICAL-ACTIVITY C1 Amer Heart Assoc, Dallas, TX 75231 USA. Amer Coll Cardiol, Bethesda, MD 20814 USA. Amer Coll Obstetricians & Gynecologists, Washington, DC 20090 USA. Amer Med Womens Assoc, Alexandria, VA 22314 USA. Assoc Black Cardiologists, Atlanta, GA 30328 USA. Ctr Dis Control & Prevent, Atlanta, GA USA. NHLBI, Bethesda, MD 20892 USA. Soc Thorac Surg, Chicago, IL 60611 USA. RP Amer Heart Assoc, Dallas, TX 75231 USA. NR 515 TC 60 Z9 63 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1079-5642 EI 1524-4636 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD MAR PY 2004 VL 24 IS 3 BP E29 EP E50 DI 10.1161/01.ATV.0000114834.85476.81 PG 22 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 800UI UT WOS:000220052800041 PM 15003974 ER PT J AU Preston, KL Urnbricht, A Schroeder, JR Abreu, ME Epstein, DH Pickworth, WB AF Preston, KL Urnbricht, A Schroeder, JR Abreu, ME Epstein, DH Pickworth, WB TI Cyclazocine: comparison to hydromorphone and interaction with cocaine SO BEHAVIOURAL PHARMACOLOGY LA English DT Article DE cyclazocine; kappa opioids; humans; opioids; cocaine; hydromorphone ID KAPPA-OPIOID RECEPTOR; DISCRIMINATIVE STIMULUS PROPERTIES; INTRAVENOUS COCAINE; NUCLEUS-ACCUMBENS; RHESUS-MONKEYS; NARCOTIC ANTAGONIST; LOCOMOTOR-ACTIVITY; OVERDOSE VICTIMS; HUMAN VOLUNTEERS; AGONIST U69593 AB Kappa-opioid agonists produce neurobiological and behavioral effects opposite to those of cocaine and may be useful for the treatment of cocaine dependence. To evaluate the kappa- and mu-agonist effects of cyclazocine and to test whether cyclazocine pretreatment would attenuate the effects of cocaine, healthy, male and female, experienced opiate and cocaine users (n=13) were enrolled in a two-phase study. In Phase 1, placebo, cyclazocine (0.2, 0.4 and 0.8 mg) and the mu-agonist hydromorphone (5 and 15 mg) were administered orally in six 4.5-hour sessions separated by at least 72 h. In Phase 2, cocaine (100 mg intranasal) was given 2 h after oral pretreatment with cyclazocine (0, 0.1, 0.2, 0.4, 0.8 and 0 mg, in that order) in each of six sessions conducted daily Monday to Friday and the following Monday. Physiological, subjective and behavioral measures were collected in each session. Nine participants completed Phase 1; eight completed Phase 2. Hydromorphone (15 mg) produced prototypic mu-agonist effects. Cyclazocine exhibited only modest kappa-like effects. Cyclazocine also had only modest, non-dose-related effects on response to cocaine. However, cocaine effects were consistently lower on the last administration (cyclazocine 0 mg pretreatment) following 4 days of cyclazocine pretreatment compared to the first administration (0 mg pretreatment). This finding is unlikely to be fully attributable to cocaine tolerance and is not accounted for by pharmacokinetic changes; plasma concentrations of cocaine were not altered by cyclazocine. This study is suggestive but not strongly supportive for the use of kappa-opiate drugs to diminish acute effects of cocaine administration or for the use of these kappa agonists in drug abuse treatment applications. C1 NIDA, Intramural Res Program, NIH, US Dept HHS, Baltimore, MD 21224 USA. RP Preston, KL (reprint author), NIDA, Intramural Res Program, NIH, US Dept HHS, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM kpreston@intra.nida.nih.gov RI Preston, Kenzie/J-5830-2013 OI Preston, Kenzie/0000-0003-0603-2479 NR 76 TC 12 Z9 13 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0955-8810 J9 BEHAV PHARMACOL JI Behav. Pharmacol. PD MAR PY 2004 VL 15 IS 2 BP 91 EP 102 DI 10.1097/01.fbp.0000125793.85076.47 PG 12 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 818WP UT WOS:000221275500001 PM 15096909 ER PT J AU Gao, ZG Jeong, LS Moon, HR Kim, HO Choi, WJ Shin, DH Elhalem, E Comin, MJ Melman, N Mamedova, L Gross, AS Rodriguez, JB Jacobson, KA AF Gao, ZG Jeong, LS Moon, HR Kim, HO Choi, WJ Shin, DH Elhalem, E Comin, MJ Melman, N Mamedova, L Gross, AS Rodriguez, JB Jacobson, KA TI Structural determinants of efficacy at A(3) adenosine receptors: modification of the ribose moiety SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE nucleosides : A(3) adenosine receptor agonist; A(3) adenosine receptor antagonist; adenylyl cyclase; phospholipase C; partial agonist ID SELECTIVE AGONISTS; HIGH-AFFINITY; IB-MECA; DERIVATIVES; LIGANDS; BINDING; A(1); ACTIVATION; INHIBITOR; ISCHEMIA AB We have found previously that structural features of adenosine derivatives, particularly at the N-6- and 2-positions of adenine, determine the intrinsic efficacy as A(3) adenosine receptor (AR) agonists. Here, we have probed this phenomenon with respect to the ribose moiety using a series of ribose-modified adenosine derivatives, examining binding affinity and activation of the human A3 AR expressed in CHO cells. Both 2'- and 3'-hydroxyl groups in the ribose moiety contribute to A(3) AR binding and activation, with 2'-OH being more essential. Thus. the 2'-fluoro substitution eliminated both binding and activation, while a 3'-fluoro substitution led to only a partial reduction of potency and efficacy at the A3 AR. A 5'-uronamide group, known to restore full efficacy in other derivatives, failed to fully overcome the diminished efficacy of 3'-fluoro derivatives. The 4'-thio substitution, which generally enhanced A3 AR potency and selectivity, resulted in 5'-CH2OH analogues (10 and 12) which were partial agonists of the A(3) AR. Interestingly, the shifting of the N-6-(3-iodobenzyl)adenine moiety from the 1'- to 4'-position had a minor influence on A3 AR selectivity, but transformed 15 into a potent antagonist (16) (K-i = 4.3 nM). Compound 16 antagonized human A(3) AR agonist-induced inhibition of cyclic AMP with a K-B value of 3.0 nM. A novel apio analogue (20) of neplanocin A, was a full A3 AR agonist. The affinities of selected, novel analogues at rat ARs were examined, revealing species differences. In summary, critical structural determinants for human A3 AR activation have been identified, which should prove useful for further understanding the mechanism of receptor activation and development of more potent and selective full agonists, partial agonists and antagonists for A3 ARs. (C) 2003 Elsevier Inc. All ri.ghts reserved. C1 NIDDKD, Bioorgan Chem Lab, Mol Recognit Sect, NIH, Bethesda, MD 20892 USA. Ewha Womans Univ, Coll Pharm, Med Chem Lab, Seoul 120750, South Korea. Univ Buenos Aires, Fac Ciencias Exactas & Nat, Dept Quim Organ, RA-1428 Buenos Aires, DF, Argentina. RP Jacobson, KA (reprint author), NIDDKD, Bioorgan Chem Lab, Mol Recognit Sect, NIH, Bethesda, MD 20892 USA. EM kajacobs@hefix.nih.gov RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031117-20] NR 29 TC 32 Z9 32 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD MAR 1 PY 2004 VL 67 IS 5 BP 893 EP 901 DI 10.1016/j.bcp.2003.10.006 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 778CY UT WOS:000189222600010 PM 15104242 ER PT J AU Sharpe, JC Arnoult, D Youle, RJ AF Sharpe, JC Arnoult, D Youle, RJ TI Control of mitochondrial permeability by Bcl-2 family members SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Review DE Bax; Bid; mitochondrion; channel ID CYTOCHROME-C RELEASE; PHOSPHOLIPID-BILAYER MEMBRANES; APOPTOSIS-INDUCING FACTOR; CHANNEL-FORMING ACTIVITY; CASPASE ACTIVATION; TRANSITION PORE; CELL-DEATH; INTRACELLULAR-LOCALIZATION; BAX OLIGOMERIZATION; PROAPOPTOTIC BAX AB Programmed cell death (apoptosis) is regulated by the Bcl-2 family of proteins. Although it remains unclear how these family members control apoptosis, they clearly have the capacity to regulate the permeability of intracellular membranes to ions and proteins. Proapoptotic members of the Bcl-2 family, especially Bax and Bid, have been extensively analyzed for the ability to form channels in membranes and to regulate preexisting channels. Anti-apoptotic members of the family tend to have the opposing effects on membrane channel formation. The molecular mechanisms of the different models for the permeabilization of membranes by the Bcl-2 family members and the regulation of Bcl-2 family member subcellular localizations are discussed. (C) 2003 Elsevier B.V. All rights reserved. C1 NINDS, Biochem Sect, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Youle, RJ (reprint author), NINDS, Biochem Sect, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. EM youle@helix.nih.gov NR 73 TC 249 Z9 269 U1 3 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4889 J9 BBA-MOL CELL RES JI Biochim. Biophys. Acta-Mol. Cell Res. PD MAR 1 PY 2004 VL 1644 IS 2-3 BP 107 EP 113 DI 10.1016/j.bbamcr.2003.10.016 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 801VE UT WOS:000220122600005 PM 14996495 ER PT J AU Akimov, SA Chimadzhev, YA Zimmerberg, J Cohen, FS Kuzmin, PI AF Akimov, SA Chimadzhev, YA Zimmerberg, J Cohen, FS Kuzmin, PI TI Line tension at a boundary of two lipid monolayers of different thickness SO BIOLOGICHESKIE MEMBRANY LA Russian DT Article ID GANGLIOSIDE GM1; RAFTS; CHOLESTEROL; MEMBRANES; DOMAINS; MODEL; BILAYERS; TILT AB The line tension (excessive energy per unit length) of the contact of two planar lipid monolayers of different equilibrium thickness is calculated. Since the exposure of hydrophobic lipid tails to water is energetically unfavorable their packing in the boundary vicinity is different from that for homogeneous monolayer. In order to diminish an area of acyl chains-water contact lipid molecules deform - compress or stretch, accumulating energy. Calculations are carried out under assumption that monolayers could be considered as a continuous elastic media characterized by two moduli of elasticity - area compression/stretching modulus K-a and tilt modulus K-t Spatial distribution of deformations and line tension are obtained by minimization of total (elastic and hydrophobic) energy. For reasonable values of the parameters it is shown that hydrophobic core-water contact is absolutely eliminated, so the energy of the system is exclusively determined by the elastic deformations of monolayers in the narrow region of similar to2-4 nm width in the vicinity of the boundary. The value of the line tension obtained is similar to0.2-0.5 kT/nm for the monolayer heights difference similar to0.3-0.5 nm. This value is sufficient to support circular shape of cholesterol-sphingomyelin domains and is in a good agreement with available experimental data. C1 Russian Acad Sci, AN Frumkin Electrochem Inst, Moscow 119071, Russia. NICHHD, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. Rush Med Coll, Dept Physiol & Mol Biophys, Chicago, IL 60612 USA. RP Akimov, SA (reprint author), Russian Acad Sci, AN Frumkin Electrochem Inst, Moscow 119071, Russia. EM krot@fromru.com RI Akimov, Sergey/L-2001-2013; Akimov, Sergey/I-6432-2015 NR 16 TC 2 Z9 2 U1 0 U2 0 PU MEZHDUNARODNAYA KNIGA PI MOSCOW PA 39 DIMITROVA UL., 113095 MOSCOW, RUSSIA SN 0233-4755 J9 BIOL MEMBRANY JI Biol. Membr. PD MAR-APR PY 2004 VL 21 IS 2 BP 151 EP 156 PG 6 WC Cell Biology SC Cell Biology GA 815AS UT WOS:000221015800009 ER PT J AU Marchetti, F Bishop, JB Cosentino, L Moore, D Wyrobek, AJ AF Marchetti, F Bishop, JB Cosentino, L Moore, D Wyrobek, AJ TI Paternally transmitted chromosomal aberrations in mouse zygotes determine their embryonic fate SO BIOLOGY OF REPRODUCTION LA English DT Article DE developmental biology; embryo; fertilization; sperm; toxicology ID MAMMALIAN GERM-CELLS; MALE-MICE; DOMINANT-LETHAL; PARENTAL ORIGIN; HERITABLE TRANSLOCATIONS; STRUCTURAL-CHANGES; HUMAN ANEUPLOIDY; DNA-REPLICATION; DOSE-RESPONSE; BONE-MARROW AB The developmental consequences of chromosomal aberrations in embryos include spontaneous abortions, morphological defects, inborn abnormalities, and genetic/chromosomal diseases. Six germ-cell mutagens with different modes of action and spermatogenic stage sensitivities were used to investigate the relationship between the types of cytogenetic damage in zygotes with their subsequent risk of postimplantation death and of birth as a translocation carrier. Independent of the mutagen used, over 98% of paternally transmitted aberrations were chromosome type, rather than chromatid type, indicating that they were formed during the period between exposure of male germ cells and initiation of the first S phase after fertilization. There were consistent one-to-one agreements between the proportions of a) zygotes with unstable aberrations and the frequencies of dead embryos after implantation (slope = 0.87, confidence interval [CI]: 0.74, 1.16) and b) zygotes with reciprocal translocations and the frequency of translocation carriers at birth (slope = 0.74, CI: 0.48, 2.11). These findings suggest that chromosomal aberrations in zygotes are highly predictive of subsequent abnormal embryonic development and that development appears to proceed to implantation regardless of the presence of chromosomal abnormalities. Our findings support the hypothesis that, for paternally transmitted chromosomal aberrations, the fate of the embryo is already set by the end of G1 of the first cell cycle of development. C1 Lawrence Livermore Natl Lab, Biol & Biotechnol Res Program, Livermore, CA 94550 USA. NIEHS, Res Triangle Pk, NC 27709 USA. Univ Calif San Francisco, Ctr Comprehens Canc, San Francisco, CA 94120 USA. RP Marchetti, F (reprint author), Lawrence Livermore Natl Lab, Biol & Biotechnol Res Program, L-488,7000 East Ave, Livermore, CA 94550 USA. EM marchetti2@llnl.gov OI Marchetti, Francesco/0000-0002-9435-4867 FU NIEHS NIH HHS [ES 09117-03, ES 8016-5] NR 68 TC 37 Z9 39 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD MAR PY 2004 VL 70 IS 3 BP 616 EP 624 DI 10.1095/biolreprod.103.023044 PG 9 WC Reproductive Biology SC Reproductive Biology GA 776ZX UT WOS:000189150400010 PM 14585809 ER PT J AU Raimondi, S Benhamou, S Coutelle, C Hayes, R Kiemeney, L Lazarus, P Le Marchand, L Morita, S Povey, A Romkes, M Zijno, A Taioli, E AF Raimondi, S Benhamou, S Coutelle, C Hayes, R Kiemeney, L Lazarus, P Le Marchand, L Morita, S Povey, A Romkes, M Zijno, A Taioli, E TI Association of metabolic gene polymorphisms with alcohol consumption in controls SO BIOMARKERS LA English DT Article DE pooled analysis; epidemiology; diet ID ALDEHYDE DEHYDROGENASE GENOTYPES; LUNG-CANCER RISK; NAD(P)H-QUINONE OXIDOREDUCTASE; CYTOCHROME P-4502E1; ADH2-ASTERISK-2 ALLELE; DRINKING BEHAVIOR; MESSENGER-RNA; JAPANESE MEN; CYP2E1 GENE; ETHANOL AB The objectives were to study the association between metabolic genes involved in alcohol metabolism (CYP2E1 RsaI, CYP2E1 DraI, ADH1C, NQO1) and alcohol consumption in a large sample of healthy controls. Healthy subjects were selected from the International Collaborative Study on Genetic Susceptibility to Environmental Carcinogens (GSEC). Subjects with information on both alcohol consumption and at least one of the studied polymorphisms were included in the analysis (n = 2224). Information on the amount of alcohol consumption was available for a subset of subjects ( n = 844). None of the studied genes was significantly associated with drinking habits. A significant heterogeneity with age was observed when studying the association between CYP2E1 RsaI and alcohol drinking. CYP2E1 RsaI polymorphism was significantly associated with being a never drinker at older ages ( odds ratio [ OR] 2.4, 95% confidence interval [CI] 1.2 - 4.8; at ages above 68 years), while the association was reversed at ages below 47 years ( OR 0.5, 95% CI 0.2 - 1.4). For subjects with detailed information on alcohol intake, no association between alcohol quantity and polymorphisms in metabolic genes was observed; subjects carrying the NQO1 polymorphism tended to drink more than subjects carrying the wild-type alleles. Therefore, no significant association between CYP2E1 RsaI, CYP2E1 DraI, ADH1C, NQO1 polymorphisms and alcohol consumption was observed in healthy controls. C1 Osped Policlin Milano, IRCCS, Mol & Genet Epidemiol Unit, I-20122 Milan, Italy. INSERM, Evry, France. Evry Univ, Evry, France. Univ Bordeaux 2, F-33076 Bordeaux, France. Genet Res Inst, Milan, Italy. NCI, Occupat & Environm Epidemiol Branch, Bethesda, MD 20892 USA. Univ Med Ctr Nijmegen, Nijmegen, Netherlands. Penn State Coll Med, Penn State Canc Inst, Hershey, PA USA. Univ Hawaii, Honolulu, HI 96822 USA. Yao Municipal Hosp, Osaka, Japan. Univ Manchester, Ctr Environm & Occupat Hlth, Manchester, Lancs, England. Univ Pittsburgh, Pittsburgh, PA USA. Ist Super Sanita, I-00161 Rome, Italy. RP Taioli, E (reprint author), Osped Policlin Milano, IRCCS, Mol & Genet Epidemiol Unit, Via F Sforza 35, I-20122 Milan, Italy. EM epidemiologia@policlinico.mi.it RI Kiemeney, Lambertus/D-3357-2009; Zijno, Andrea/H-9562-2014; Raimondi, Sara/J-5236-2016; OI Kiemeney, Lambertus/0000-0002-2368-1326; Raimondi, Sara/0000-0003-4673-9049; Garte, Seymour/0000-0003-3284-5975; Hayes, Richard/0000-0002-0918-661X NR 47 TC 3 Z9 4 U1 0 U2 2 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1354-750X J9 BIOMARKERS JI Biomarkers PD MAR PY 2004 VL 9 IS 2 BP 180 EP 189 DI 10.1080/13547500410001728381 PG 10 WC Biotechnology & Applied Microbiology; Toxicology SC Biotechnology & Applied Microbiology; Toxicology GA 847OQ UT WOS:000223405200005 PM 15370874 ER PT J AU Washburn, NR Yamada, KM Simon, CG Kennedy, SB Amis, EJ AF Washburn, NR Yamada, KM Simon, CG Kennedy, SB Amis, EJ TI High-throughput investigation of osteoblast response to polymer crystallinity: influence of nanometer-scale roughness on proliferation SO BIOMATERIALS LA English DT Article DE cell proliferation; crystallinity; osteoblast; nanotopography ID IN-VITRO; CELL-GROWTH; FIBRONECTIN; SURFACES; BIOCOMPATIBILITY; PHOSPHORYLATION; SUBSTRATUM; EXPRESSION; PAXILLIN; PROTEINS AB A high-throughput method for analyzing cellular response to crystallinity in a polymer material is presented. Variations in crystallinity lead to changes in surface roughness on nanometer length scales, and it is shown that cells are exquisitely sensitive to these changes. Gradients of polymer crystallinity were fabricated on films Of poly(L-lactic acid) using a gradient in annealing temperature. The resultant morphologies were characterized using an atomic force microscope. Root-mean-square (rms) roughness values ranging from 0.5 to 13 nm were created on a single sample. MCM-E1 osteoblastic cells were cultured for 1, 3 and 5 d, and the number of cells was measured using automated fluorescence microscopy. It is shown that the rate of proliferation on the smooth regions of the films is much greater than that on the rough regions, and a monotonic variation in rate is observed as a function of roughness. The critical rms roughness, above which a statistically significant reduction in rate of proliferation occurs, was approximately 1.1 nm. Fluorescence microscopy measurements on immunostained cells indicate there is no significant change in cell area, the number or type of adhesions formed, or the degree of actin polymerization. Results from enzyme-linked immunofluorescence assays indicated that there was no detectable change in adhesion protein accessibility, suggesting the cells directly respond to substrate topography. The use of the gradient library approach yielded the functional dependence of cell proliferation on nanometer-scale roughness and gave a sensitive estimate of the critical roughness for which a decrease in proliferation is observed. (C) 2003 Elsevier Ltd. All rights reserved. C1 Natl Inst Stand & Technol, Div Polymers, Gaithersburg, MD 20899 USA. Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. RP Washburn, NR (reprint author), Natl Inst Stand & Technol, Div Polymers, Gaithersburg, MD 20899 USA. RI Luong-Van, Emma/A-8685-2012; OI Yamada, Kenneth/0000-0003-1512-6805 NR 26 TC 185 Z9 188 U1 5 U2 32 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 J9 BIOMATERIALS JI Biomaterials PD MAR-APR PY 2004 VL 25 IS 7-8 BP 1215 EP 1224 DI 10.1016/j.biomaterials.2003.08.043 PG 10 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 753PJ UT WOS:000187239500009 PM 14643595 ER PT J AU Freedman, LS Fainberg, V Kipnis, V Midthune, D Carroll, RJ AF Freedman, LS Fainberg, V Kipnis, V Midthune, D Carroll, RJ TI A new method for dealing with measurement error in explanatory variables of regression models SO BIOMETRICS LA English DT Article DE case-control study; classification trees; cohort study; errors-in-variables; linear discriminant analysis; logistic regression; measurement error; regression calibration ID LOGISTIC-REGRESSION; SERUM AB We introduce a new method, moment reconstruction, of correcting for measurement error in covariates in regression models. The central idea is similar to regression calibration in that the values of the covariates that are measured with error are replaced by "adjusted" values. In regression calibration the adjusted value is the expectation of the true value conditional on the measured value. In moment reconstruction the adjusted value is the variance-preserving empirical Bayes estimate of the true value conditional on the outcome variable. The adjusted values thereby have the same first two moments and the same covariance with the outcome variable as the unobserved "true" covariate values. We show that moment reconstruction is equivalent to regression calibration in the case of linear regression, but leads to different results for logistic regression. For case-control studies with logistic regression and covariates that are normally distributed within cases and controls, we show that the resulting estimates of the regression coefficients are consistent. In simulations we demonstrate that for logistic regression, moment reconstruction carries less bias than regression calibration, and for case-control studies is superior in mean-square error to the standard regression calibration approach. Finally, we give an example of the use of moment reconstruction in linear discriminant analysis and a nonstandard problem where we wish to adjust a classification tree for measurement error in the explanatory variables. C1 Bar Ilan Univ, Dept Math & Stat, IL-52900 Ramat Gan, Israel. NCI, Biometry Res Grp, Div Canc Prevent, Bethesda, MD 20892 USA. Texas A&M Univ, Dept Stat, College Stn, TX 77843 USA. RP Freedman, LS (reprint author), Bar Ilan Univ, Dept Math & Stat, IL-52900 Ramat Gan, Israel. EM freedml@macs.biu.ac.il FU NCI NIH HHS [CA-57030]; NIEHS NIH HHS [P30-ES09106] NR 18 TC 22 Z9 22 U1 0 U2 6 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0006-341X J9 BIOMETRICS JI Biometrics PD MAR PY 2004 VL 60 IS 1 BP 172 EP 181 DI 10.1111/j.0006-341X.2004.00164.x PG 10 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 805RW UT WOS:000220384400021 PM 15032787 ER PT J AU Pinsky, PF AF Pinsky, PF TI An early- and late-stage convolution model for disease natural history SO BIOMETRICS LA English DT Article DE cancer; lead time; natural history; screening; stage ID PROSTATE-CANCER; SCREENING PROGRAMS; LEAD-TIME AB The standard convolution model of disease natural history posits an asymptomatic (preclinical) and a symptomatic (clinical) state. An augmented model includes, in both the preclinical and clinical states, an early and late stage of disease. In the case of cancer, the early stage would generally correspond to the organ-confined stages before there is evidence of cancer spread. We compute the number of screen-detected (preclinical) and clinical cases in the early and late stages expected under a given screening program and show how the model can be fit to data from a screening trial using maximum likelihood. We also develop expressions for sojourn time, lead time, and overdiagnosis in the context of the model, where each of the above concepts incorporates disease stage. As an example, we fit the model to data from the Mayo Lung Cancer Screening trial. C1 NCI, Div Canc Prevent, Bethesda, MD 20892 USA. RP Pinsky, PF (reprint author), NCI, Div Canc Prevent, 6130 Executive Blvd,EPN 3064, Bethesda, MD 20892 USA. EM pinskyp@mail.nih.gov NR 12 TC 7 Z9 7 U1 0 U2 2 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0006-341X J9 BIOMETRICS JI Biometrics PD MAR PY 2004 VL 60 IS 1 BP 191 EP 198 DI 10.1111/j.0006-341X.2004.00023.x PG 8 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 805RW UT WOS:000220384400023 PM 15032789 ER PT J AU Pfeiffer, RM Mbulaiteye, S Engels, E AF Pfeiffer, RM Mbulaiteye, S Engels, E TI A model to estimate risk of infection with human herpesvirus 8 associated with transfusion from cross-sectional data SO BIOMETRICS LA English DT Article DE age at transfusion data; current-status data; mixture models; multistate models ID DISEASE AB In cross-Sectional studies of infectious diseases, the data typically consist of: age at the time of study, status (presence or absence) of infection, and a chronology of events possibly associated with the disease. Motivated by a study of how human herpesvirus 8 (HHV-8) is transmitted among children with sickle cell anemia in Uganda, we have developed a flexible parametric approach for combining current-status data with a history of blood transfusions. We model heterogeneity in transfusion- associated risk by a child-specific random effect. We present an extension of the model to accommodate the fact that there is no gold standard for HHV-8 infection and infection status was assessed by a serological assay. The parameters are estimated via maximum likelihood. Finally, we present results from applying various parameterizations of the model to the Ugandan study. C1 NCI, Biostat Branch, Bethesda, MD 20892 USA. NCI, Viral Epidemiol Branch, Bethesda, MD 20892 USA. RP Pfeiffer, RM (reprint author), NCI, Biostat Branch, Bethesda, MD 20892 USA. EM pfeiffer@mail.nih.gov RI Pfeiffer, Ruth /F-4748-2011 NR 17 TC 6 Z9 6 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0006-341X J9 BIOMETRICS JI Biometrics PD MAR PY 2004 VL 60 IS 1 BP 249 EP 256 DI 10.1111/j.0006-341X.2004.00168.x PG 8 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 805RW UT WOS:000220384400030 PM 15032796 ER PT J AU Schenck, HA Lenkowski, PW Choudhury-Mukherjee, I Ko, SH Stables, JP Patel, MK Brown, ML AF Schenck, HA Lenkowski, PW Choudhury-Mukherjee, I Ko, SH Stables, JP Patel, MK Brown, ML TI Design, synthesis and evaluation of novel hydroxyamides as orally available anticonvulsants SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE amides; alcohols; ion channel; calcium channel ID CALCIUM CHANNELS; EPILEPSY; DERIVATIVES; ACRYLAMIDE; MECHANISMS; RECEPTOR; KETONES; BINDING; ACID AB Themisone, also known as Atrolactamide, was found, in the 1950s, to be a very potent anticonvulsant. It was hypothesized that the -CF3 substitution would maintain the anticonvulsant activity. Anticonvulsant testing of our novel compounds by the National Institute of Health's Anticonvulsant Screening Project of the Antiepileptic Drug Discovery Program identified analogue 1, 3,3,3-trifluoro-2-hydroxy-2-phenyi-propionamide, to have potent anticonvulsant activity (MES ED50 of 9.9 mg/kg, ScMET ED50 of 34 mg/kg and TD50 of 100 mg/kg). Therefore, a diverse range of analogues were synthesized utilizing multiple synthetic pathways to explore the structure-activity relationship. Patch clamp electrophysiology experiments demonstrate that compound 1 is an effective T-type calcium channel blocker. Altogether, these results suggest these compounds as a class of orally available anticonvulsants. (C) 2003 Published by Elsevier Ltd. C1 Univ Virginia, Dept Chem, Charlottesville, VA 22904 USA. Univ Virginia, Dept Anesthesiol, Charlottesville, VA 22908 USA. NIH, Div Neurol Dis & Stroke, Bethesda, MD 20824 USA. RP Brown, ML (reprint author), Univ Virginia, Dept Chem, Mccormick Rd,POB 400319, Charlottesville, VA 22904 USA. NR 28 TC 56 Z9 57 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD MAR 1 PY 2004 VL 12 IS 5 BP 979 EP 993 DI 10.1016/j.bmc.2003.12.011 PG 15 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 779RQ UT WOS:000189314700017 PM 14980611 ER PT J AU Lee, J Kim, SY Park, S Lim, JO Kim, JM Kang, M Lee, J Kang, SU Choi, HK Jin, MK Welter, JD Szabo, T Tran, R Pearce, LV Toth, A Blumberg, PM AF Lee, J Kim, SY Park, S Lim, JO Kim, JM Kang, M Lee, J Kang, SU Choi, HK Jin, MK Welter, JD Szabo, T Tran, R Pearce, LV Toth, A Blumberg, PM TI Structure-activity relationships of simplified resiniferatoxin analogues with potent VR1 agonism elucidates an active conformation of RTX for VR1 binding SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE vanilloid receptor 1; resiniferatoxin ID VANILLOID RECEPTOR AGONISTS; HIGH-AFFINITY ANTAGONISTS; ROOT GANGLION NEURONS; CAPSAICIN RECEPTOR; DIRECT PHOSPHORYLATION; ANALGESIC AGENTS; PAIN; ACID; PHARMACOLOGY; SENSITIVITY AB We previously described a series of N-(3-acyloxy-2-benzylpropyl) homovanillate and N'-(4-hydroxy-3-methoxybenzyl) thiourea derivatives that were potent VR1 agonists with high-affinities and excellent analgesic profiles. The design of these simplified RTX analogues was based on our RTX-derived pharmacophore model which incorporates the 4-hydroxy-3-methoxyphenyl (A-region), C-20-ester (B-region), orthophenyl (C1-region) and C-3-keto (C2-region) groups of RTX. For the purpose of optimizing the spatial arrangement of the four principal pharmacophores on the lead agonists (1-4), we have modified the distances in the parent C-region, 3-acyloxy-2-benzylpropyl groups, by lengthening or shortening one carbon to vary the distances between the pharmacophores. We find that two of the amides, 4 and 19, possess EC50 values < 1 nM for induction of calcium influx in the VR1-CHO cells. As observed previously, the structure-activity relations for inhibition of RTX binding to VR1 and for induction of calcium uptake were distinct, presumably reflecting both intrinsic and methodological factors. In order to find the active conformation of VR1 ligands, the energy-minimized conformations of seven selected agonists were determined and the positions of their four pharmacophores were matched with those of five low energy RTX conformations. The rms values for the overlaps in the pharmacophores were calculated and correlated with the measured binding affinities (K-i) and calcium influx (EC50) values. The binding affinities of the agonists correlated best with the RMS values derived from RTX conformation E (r(2) = 0.92), predicting a model of the active conformation of RTX and related vanilloids for binding to VR1. Poorer correlation was obtained between any of the conformations and the EC50 values for calcium influx. (C) 2004 Elsevier Ltd. All rights reserved. C1 Seoul Natl Univ, Coll Pharm, Pharmaceut Sci Res Inst, Med Chem Lab, Seoul 151742, South Korea. NCI, Canc Res Ctr, Cellular Carcinogenesis & Tumor Promot Lab, NIH, Bethesda, MD 20892 USA. RP Lee, J (reprint author), Seoul Natl Univ, Coll Pharm, Pharmaceut Sci Res Inst, Med Chem Lab, Shinlim Dong, Seoul 151742, South Korea. EM jeewoo@snu.ac.kr RI Toth, Attila/F-4859-2010; Kang, Myungshim /K-5331-2014; OI Toth, Attila/0000-0001-6503-3653; Kang, Myungshim /0000-0002-4778-8240; Lee, Jiyoun/0000-0003-3819-5889 NR 41 TC 10 Z9 11 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD MAR 1 PY 2004 VL 12 IS 5 BP 1055 EP 1069 DI 10.1016/j.bmc.2003.12.005 PG 15 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 779RQ UT WOS:000189314700025 PM 14980619 ER PT J AU Zorrilla, S Jimenez, M Lillo, P Rivas, GN Minton, AR AF Zorrilla, S Jimenez, M Lillo, P Rivas, GN Minton, AR TI Sedimentation equilibrium in a solution containing an arbitrary number of solute species at arbitrary concentrations: theory and application to concentrated solutions of ribonuclease SO BIOPHYSICAL CHEMISTRY LA English DT Article DE thermodynamic nonideality; reversible association; ribonuclease ID SELF-ASSOCIATION; ANALYTICAL ULTRACENTRIFUGATION; THERMODYNAMIC NONIDEALITY; MACROMOLECULAR SOLUTIONS; HEMOGLOBIN-S; PROTEIN; CONSEQUENCES; VOLUME; CYTOPLASM; DIMER AB Simple expressions are derived describing the equilibrium concentration gradient of each species in a solution containing an arbitrary number of solute species at arbitrary concentration, as a function of the concentration of all species. Quantitative relationships between the species gradients and experimentally observable signal gradients are presented. The expressions are model-free and take into account both attractive and repulsive interactions between all species. In order to analyze data obtained from strongly nonideal solutions, a statistical thermodynamic model for repulsive solute-solute interactions is required. The relations obtained are utilized to analyze the dependence of the equilibrium gradient of ribonuclease A in phosphate-buffered saline, pH 7.4, upon total protein concentration. Experimental results are interpreted in the context of a model for weak self-association leading to the formation of significant amounts of oligomers at total protein concentrations exceeding 25 g/l. (C) 2003 Elsevier B.V. All rights reserved. C1 NIH, Lab Biochem & Genet, Bethesda, MD 20892 USA. CSIC, Inst Quim Fis Rocasolano, E-28006 Madrid, Spain. CSIC, Ctr Invest Biol, E-28006 Madrid, Spain. RP Minton, AR (reprint author), NIH, Lab Biochem & Genet, Bldg 8,Room 226, Bethesda, MD 20892 USA. EM minton@helix.nih.gov RI Zorrilla, Silvia/J-9771-2014; Jimenez Sarmiento, Mercedes/K-2691-2014; Lillo, M. Pilar/O-2556-2013; OI Zorrilla, Silvia/0000-0002-6309-9058; Jimenez Sarmiento, Mercedes/0000-0003-2006-1903; Lillo, M. Pilar/0000-0001-8582-4591; Minton, Allen/0000-0001-8459-1247; Rivas, German/0000-0003-3450-7478 NR 36 TC 27 Z9 27 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-4622 J9 BIOPHYS CHEM JI Biophys. Chem. PD MAR 1 PY 2004 VL 108 IS 1-3 BP 89 EP 100 DI 10.1016/j.bpc.2003.10.012 PG 12 WC Biochemistry & Molecular Biology; Biophysics; Chemistry, Physical SC Biochemistry & Molecular Biology; Biophysics; Chemistry GA 808VE UT WOS:000220595800009 PM 15043923 ER PT J AU Schuck, P AF Schuck, P TI A model for sedimentation in inhomogeneous media. I. Dynamic density gradients from sedimenting co-solutes SO BIOPHYSICAL CHEMISTRY LA English DT Article DE sedimentation velocity; analytical ultracentrifugation; finite element methods; density gradient centrifugation; isopycnic separation; size distributions; Lamm equation ID PROTEIN-PROTEIN INTERACTIONS; SIZE-DISTRIBUTION ANALYSIS; ANALYTICAL ULTRACENTRIFUGATION; LAMM EQUATION; INTERACTING PARTICLES; VELOCITY EXPERIMENTS; GENERALIZED SYSTEMS; SUCROSE GRADIENTS; DNA; COEFFICIENTS AB Macromolecular sedimentation in inhomogeneous media is of great practical importance. Dynamic density gradients have a long tradition in analytical ultracentrifugation, and are frequently used in preparative ultracentrifugation. In this paper, a new theoretical model for sedimentation in inhomogeneous media is presented, based on finite element solutions of the Lamm equation with spatial and temporal variation of the local solvent density and viscosity. It is applied to macromolecular sedimentation in the presence of a dynamic density gradient formed by the sedimentation of a co-solute at high concentration. It is implemented in the software SEDFIT for the analysis of experimental macromolecular concentration distributions. The model agrees well with the measured sedimentation profiles of a protein in a dynamic cesium chloride gradient, and may provide a measure for the effects of hydration or preferential solvation parameters. General features of protein sedimentation in dynamic density gradients are described. (C) 2003 Published by Elsevier B.V. C1 NIH, OD, ORS, Div Bioengn & Phys Sci, Bethesda, MD 20892 USA. RP Schuck, P (reprint author), NIH, OD, ORS, Div Bioengn & Phys Sci, Bldg 13,Room 3N17,13 South Dr, Bethesda, MD 20892 USA. EM pschuck@helix.nih.gov OI Schuck, Peter/0000-0002-8859-6966 NR 51 TC 51 Z9 51 U1 3 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-4622 EI 1873-4200 J9 BIOPHYS CHEM JI Biophys. Chem. PD MAR 1 PY 2004 VL 108 IS 1-3 BP 187 EP 200 DI 10.1016/j.bpc.2003.10.016 PG 14 WC Biochemistry & Molecular Biology; Biophysics; Chemistry, Physical SC Biochemistry & Molecular Biology; Biophysics; Chemistry GA 808VE UT WOS:000220595800015 PM 15043929 ER PT J AU Schuck, P AF Schuck, P TI A model for sedimentation in inhomogeneous media. II. Compressibility of aqueous and organic solvents SO BIOPHYSICAL CHEMISTRY LA English DT Article DE sedimentation velocity; analytical ultracentrifugation; finite element methods; density gradient centrifugation; compressible solvents; size distributions; polymers; Lamm equation ID RAPID PRECISION INTERFEROMETRY; SIZE-DISTRIBUTION ANALYSIS; ANALYTICAL ULTRACENTRIFUGATION; LAMM EQUATION; COEFFICIENT DISTRIBUTION; DIFFERENTIAL-EQUATION; MALATE-DEHYDROGENASE; VELOCITY EXPERIMENTS; GLOBULAR-PROTEINS; BOUNDARY ANALYSIS AB The effects of solvent compressibility on the sedimentation behavior of macromolecules as observed in analytical ultracentrifugation are examined. Expressions for the density and pressure distributions in the solution column are derived and combined With the finite element solution of the Lamm equation in inhomogeneous media to predict the macromolecular concentration distributions under different conditions. Independently, analytical expressions are derived for the sedimentation of non-diffusing particles in the limit of low compressibility Both models are quantitatively consistent and predict solvent compressibility to result in, a reduction of the sedimentation rate along the solution column and a continuous accumulation of solutes in the plateau region. For both organic and aqueous solvents, the calculated deviations from the sedimentation in incompressible media can be very large and substantially above the measurement error. Assuming conventional configurations used for sedimentation velocity experiments in analytical ultracentrifugation, neglect of the compressibility of water leads to systematic errors underestimating sedimentation coefficients by approximately 1% at a rotor speeds of 45 000 rpm, but increasing to 2-5% with increasing rotor speeds and decreasing macromolecular. size. The proposed finite element solution of the Lamm equation can be used to take solvent compressibility quantitatively into account in direct boundary models for discrete species, sedimentation coefficient distributions or molar mass distributions. Using the analytical expressions for the sedimentation of non-diffusing particles, the Is-g*(s) distribution of apparent sedimentation coefficients is extended to the analysis of sedimentation in compressible solvents. The consideration of solvent compressibility is highly relevant not only when using organic solvents, but also in aqueous solvents when precise sedimentation coefficients are needed, for example, for hydrodynamic modeling. (C) 2003 Published by Elsevier B.V. C1 NIH, OD, ORS, Div Bioengn & Phys Sci, Bethesda, MD 20892 USA. RP Schuck, P (reprint author), NIH, OD, ORS, Div Bioengn & Phys Sci, Bldg 13,Rm 3N17,13 South Dr, Bethesda, MD 20892 USA. EM pschuck@helix.nih.gov OI Schuck, Peter/0000-0002-8859-6966 NR 61 TC 20 Z9 20 U1 2 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-4622 J9 BIOPHYS CHEM JI Biophys. Chem. PD MAR 1 PY 2004 VL 108 IS 1-3 BP 201 EP 214 DI 10.1016/j.bpc.2003.10.017 PG 14 WC Biochemistry & Molecular Biology; Biophysics; Chemistry, Physical SC Biochemistry & Molecular Biology; Biophysics; Chemistry GA 808VE UT WOS:000220595800016 PM 15043930 ER PT J AU Petrache, HI Tristram-Nagle, S Gawrisch, K Harries, D Parsegian, VA Nagle, JF AF Petrache, HI Tristram-Nagle, S Gawrisch, K Harries, D Parsegian, VA Nagle, JF TI Structure and fluctuations of charged phosphatidylserine bilayers in the absence of salt SO BIOPHYSICAL JOURNAL LA English DT Article ID PROTEIN-KINASE-C; X-RAY-DIFFRACTION; NUCLEAR-MAGNETIC-RESONANCE; THERMAL-MECHANICAL FLUCTUATIONS; GIANT COLLECTIVE FLUCTUATIONS; VESICLE UNBINDING TRANSITION; H-2 NMR-SPECTROSCOPY; LIPID-BILAYERS; ACYL-CHAIN; PHOSPHOLIPID-BILAYERS AB Using x-ray diffraction and NMR spectroscopy, we present structural and material properties of phosphatidylserine (PS) bilayers that may account for the well documented implications of PS headgroups in cell activity. At 30degreesC, the 18-carbon monounsaturated DOPS in the fluid state has a cross-sectional area of 65.3 Angstrom(2) which is remarkably smaller than the area 72.5 Angstrom(2) of the DOPC analog, despite the extra electrostatic repulsion expected for charged PS headgroups. Similarly, at 20degreesC, the 14-carbon disaturated DMPS in the gel phase has an area of 40.8 Angstrom(2) vs. 48.1 Angstrom(2) for DMPC. This condensation of area suggests an extra attractive interaction, perhaps hydrogen bonding, between PS headgroups. Unlike zwitterionic lipids, stacks of PS bilayers swell indefinitely as water is added. Data obtained for osmotic pressure versus interbilayer water spacing for fluid phase DOPS are well fit by electrostatic interactions calculated for the Gouy-Chapman regime. It is shown that the electrostatic interactions completely dominate the fluctuational pressure. Nevertheless, the x-ray data definitively exhibit the effects of fluctuations in fluid phase DOPS. From our measurements of fluctuations, we obtain the product of the bilayer bending modulus K-c and the smectic compression modulus B. At the same interbilayer separation, the interbilayer fluctuations are smaller in DOPS than for DOPC, showing that B and/or K-c are larger. Complementing the x-ray data, P-31-chemical shift anisotropy measured by NMR suggest that the DOPS headgroups are less sensitive to osmotic pressure than DOPC headgroups, which is consistent with a larger K-c in DOPS. Quadrupolar splittings for D2O decay less rapidly with increasing water content for DOPS than for DOPC, indicating greater perturbation of interlamellar water and suggesting a greater interlamellar hydration force in DOPS. Our comparisons between bilayers of PS and PC lipids with the same chains and the same temperature enable us to focus on the effects of these headgroups on bilayer properties. C1 NICHHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. Carnegie Mellon Univ, Dept Biol Sci, Pittsburgh, PA 15213 USA. NIAAA, Dept Biol Sci, NIH, Rockville, MD 20852 USA. Carnegie Mellon Univ, Dept Phys, Pittsburgh, PA 15213 USA. RP Petrache, HI (reprint author), NICHHD, Lab Phys & Struct Biol, NIH, Bldg 9,Rm 1E116, Bethesda, MD 20892 USA. EM horia@helix.nih.gov RI Harries, Daniel/F-7016-2012; Tristram-Nagle, Prof. Stephanie/N-7811-2014; Nagle, John/B-1917-2015 OI Harries, Daniel/0000-0002-3057-9485; Tristram-Nagle, Prof. Stephanie/0000-0003-2271-7056; Nagle, John/0000-0002-9844-5934 FU NIGMS NIH HHS [GM44976, R01 GM044976] NR 78 TC 169 Z9 170 U1 4 U2 56 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD MAR PY 2004 VL 86 IS 3 BP 1574 EP 1586 DI 10.1016/S0006-3495(04)74225-3 PG 13 WC Biophysics SC Biophysics GA 780JK UT WOS:000189377400026 PM 14990484 ER PT J AU Zhang, J Troendle, J Meikle, S Klebanoff, MA Rayburn, WF AF Zhang, J Troendle, J Meikle, S Klebanoff, MA Rayburn, WF TI Isolated oligohydramnios is not associated with adverse perinatal outcomes SO BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY LA English DT Article ID AMNIOTIC-FLUID INDEX; WEEKS GESTATION; HIGH-RISK; ANTEPARTUM; PREGNANCY; PREDICTION; WEIGHT; VOLUME; GROWTH AB Objective To examine fetal growth and perinatal outcomes in pregnancies with isolated oligohydramnios. Design A cohort study. Setting Multiple clinics and hospitals. Population Low risk pregnant women. Methods We used data from the multicentre clinical trial of Routine Antenatal Diagnostic Imaging with UltraSound (RADIUS), in which 15,151 low risk pregnant women were randomly assigned to the ultrasound screening group or the control group. Women in the screening group underwent sonographic exams at 15-22 and 31-35 weeks of gestation. Both groups could have clinically indicated sonographic exams at any rime. Main outcome measures We used changes of fetal weight z-score to assess whether fetal growth was compromised from the diagnosis of oligohydramnios until delivery, using a repeated-measures regression. We used a combined perinatal index as an indicator of adverse perinatal outcome, which consisted of severe perinatal morbidity and mortality. Results Oligohydramnios (amniotic fluid index less than or equal to 5 cm) was diagnosed in 1.5% (113/7617) of women with ultrasound screening compared with 0.8% (57/7534) among the controls. Approximately half of the oligohydramnios cases in the screening group were isolated with no clearly associated factors (e.g. premature rupture of the fetal membranes, congenital anomalies, diabetes, hypertension, postdate and intrauterine growth restriction). Fetal weight centiles in isolated oligohydramnios cases did not change significantly from diagnosis until delivery. Pregnancies with isolated oligohydramnios had perinatal outcomes similar to pregnancies with a normal amniotic fluid index. Conclusion Isolated oligohydramnios is not associated with impaired fetal growth or an increased risk of adverse perinatal outcomes. C1 NICHHD, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, Dept Hlth & Human Serv,NIH, Bethesda, MD 20892 USA. NICHHD, Ctr Res Mothers & Children, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. Univ New Mexico, Hlth Sci Ctr, Dept Obstet & Gynecol, Albuquerque, NM 87131 USA. RP Zhang, J (reprint author), NICHHD, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, Dept Hlth & Human Serv,NIH, NIH Bldg 6100,Room 7B03, Bethesda, MD 20892 USA. FU NICHD NIH HHS [HD 19897, HD 21017, HD 21140] NR 18 TC 44 Z9 53 U1 0 U2 3 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 1470-0328 J9 BJOG-INT J OBSTET GY JI BJOG PD MAR PY 2004 VL 111 IS 3 BP 220 EP 225 DI 10.1111/j.1471-0528.2004.00060.x PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 780CQ UT WOS:000189354100006 PM 14961882 ER PT J AU Markovic, I Stantchev, TS Fields, KH Tiffany, LJ Tomic, M Weiss, CD Broder, CC Strebel, K Clouse, KA AF Markovic, I Stantchev, TS Fields, KH Tiffany, LJ Tomic, M Weiss, CD Broder, CC Strebel, K Clouse, KA TI Thiol/disulfide exchange is a prerequisite for CXCR4-tropic HIV-1 envelope-mediated T-cell fusion during viral entry SO BLOOD LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; PROTEIN-DISULFIDE-ISOMERASE; MEMBRANE-FUSION; PLASMA-MEMBRANE; INFLUENZA HEMAGGLUTININ; DETERGENT-RESISTANT; SURFACE ASSOCIATION; LIPID RAFTS; CD4; MICRODOMAINS AB Attachment of gp120 to CD4 during HIV-1 entry triggers structural rearrangement in gp120 that enables binding to an appropriate coreceptor. Following coreceptor engagement, additional conformational changes occur in the envelope (Env), resulting in fusion of virion and cell membranes. Catalysts with redox-isomerase activity, such as protein disulfide isomerase (PDI), facilitate Env conversion from its inactive to its fusion-competent conformation. We report here that anti-PDI agents effectively block CXCR4 Env-mediated fusion and spread of virus infection. Exogenously added PDI, in turn, can rescue fusion from this blockade. We further find that PDI facilitates thiol/disulfide rearrangement in gp120 during conformational change, whereas inhibition of this redox shuffling prevents gp41 from assuming the fusogenic 6-helix bundle conformation. At the virus-cell contact site, gp120 induces assembly of PDI, CD4, and CXCR4 into a tetramolecular protein complex serving as a portal for viral entry. Our findings support the hypothesis that Env conformational change depends on a well-coordinated action of a tripartite system in which PDI works in concert with the receptor and the coreceptor to effectively lower the activation energy barrier required for Env conformational rearrangement. (C) 2004 by The American Society of Hematology. C1 CDER, Bethesda, MD USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. Uniformed Serv Univ Hlth Sci, F Edward Hebert Sch Med, Bethesda, MD 20814 USA. NICHHD, Bethesda, MD 20892 USA. NIAID, NIH, Bethesda, MD 20892 USA. RP Markovic, I (reprint author), Bldg 29B,Rm 3E18,29 Lincoln Dr, Bethesda, MD 20892 USA. EM markovic@cber.fda.gov RI Weiss, Carol/F-6438-2011; Tomic, Melanija/C-3371-2016 OI Weiss, Carol/0000-0002-9965-1289; NR 44 TC 90 Z9 96 U1 0 U2 7 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAR 1 PY 2004 VL 103 IS 5 BP 1586 EP 1594 DI 10.1182/blood-2003-05-1390 PG 9 WC Hematology SC Hematology GA 778NM UT WOS:000189247700013 PM 14592831 ER PT J AU Bhanu, NV Trice, TA Lee, YT Miller, JL AF Bhanu, NV Trice, TA Lee, YT Miller, JL TI A signaling mechanism for growth-related expression of fetal hemoglobin SO BLOOD LA English DT Article ID ACTIVATED PROTEIN-KINASE; STEM-CELL FACTOR; ERYTHROID PROGENITOR CELLS; DEPENDENT ACTIVATION; SODIUM-BUTYRATE; NITRIC-OXIDE; ERYTHROPOIESIS; ADULT; PHOSPHORYLATION; INHIBITION AB Increases in fetal hemoglobin have been identified after birth in several clinical settings associated with stressed or malignant erythropoiesis. To better understand the relationship between the expression of this fetal protein and growth, donated human erythrold progenitor cells were cultured in the presence of erythropoietin (EPO) plus the growth-modifying cytokine stem cell factor (SCF), and several growth-related signaling pathways were interrogated. Only the MEK1/2 inhibitor (PD98059) demonstrated significant effects on fetal hemoglobin. In the absence of PD98059, levels of fetal hemoglobin averaged 27.4% +/- 7.9% in EPO+SCF compared with 1.26% +/- 1.7% in EPO alone (P = .02). A linear dose response in levels of fetal hemoglobin to PD98059 was detected (0.16 muM = 27.13%, 0.8 muM = 19.6%, 4 muM = 12.2%, 20 muM = 1.54%). Western blot analyses revealed that SCF was required for phosphorylation of MEK and p44MAPK in this setting, and quantitative polymerase chain reaction demonstrated a significant increase in gamma-globin mRNA. Particular perturbations of growth-related signaling may also function to activate tissue-specific genes normally expressed during fetal development. This concept may be relevant for the development of new treatment rationales for beta hemoglobinopathies. (C) 2004 by The American Society of Hematology. C1 NIDDKD, Biol Chem Lab, NIH, Bethesda, MD 20892 USA. RP Miller, JL (reprint author), NIDDKD, Biol Chem Lab, NIH, Bethesda, MD 20892 USA. EM jm7f@nih.gov NR 37 TC 26 Z9 26 U1 1 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAR 1 PY 2004 VL 103 IS 5 BP 1929 EP 1933 DI 10.1182/blood-2003-05-1624 PG 5 WC Hematology SC Hematology GA 778NM UT WOS:000189247700060 PM 14592835 ER PT J AU Socie, G Rosenberg, P Gluckman, E Alter, B AF Socie, G Rosenberg, P Gluckman, E Alter, B TI How can we quantify the risk of squamous cell cancer (SCC) and death in transplanted versus non-transplanted patients with Fanconi's Anaemia SO BONE MARROW TRANSPLANTATION LA English DT Meeting Abstract CT 30th Annual Meeting of the European-Group-for-Blood-and-Marrow-Transplantation/20th Meeting of the EBMT-Nurses-Group/3rd Meeting of the EBMT-Data-Management-Group CY MAR 28-31, 2004 CL Barcelona, SPAIN SP European Grp Blood & Marrow Transplantat, EBMT Nurses Grp, EBMT Data management Grp C1 Hop St Louis, Paris, France. NCI, Rockville, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD MAR PY 2004 VL 33 SU 1 BP S27 EP S27 PG 1 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 812PH UT WOS:000220850900074 ER PT J AU Ramsey, NF Jansma, JM Jager, G Van Raalten, T Kahn, RS AF Ramsey, NF Jansma, JM Jager, G Van Raalten, T Kahn, RS TI Neurophysiological factors in human information processing capacity SO BRAIN LA English DT Article DE working memory; information processing capacity; fMRI; individual variation; multitasking; automatization ID WORKING-MEMORY; NEURAL BASIS; INDIVIDUAL-DIFFERENCES; VISUAL EXPERIENCE; PREFRONTAL CORTEX; BRAIN ACTIVITY; TASK; FMRI; AUTOMATIZATION; PERFORMANCE AB What determines how well an individual can manage the complexity of information processing demands when several tasks have to be executed simultaneously? Various theoretical frameworks address the mechanisms of information processing and the changes that take place when processes become automated, and brain regions involved in various types of information processing have been identified, as well as sequences of events in the brain. The neurophysiological substrate of human information processing capacity, i.e. the amount that can be processed simultaneously, is, however, unresolved, as is the basis of inter-individual variability in capacity. Automatization of cognitive functions is known to increase capacity to process additional tasks, but behavioural indices of automatization are poor predictors of processing capacity in individuals. Automatization also leads to a decline of brain activity in the working memory system. In this study, we test the hypothesis that processing capacity is closely related to the way that the brain adjusts to practice of a single cognitive task, i.e. to the changes in neuronal activity that accompany automatization as measured with functional MRI (fMRI). Using a task that taxes the working memory system, and is sensitive to automatization, performance improved while activity in the network declined, as expected. The key finding is that the magnitude of automatization-induced reduction of activity in this system was a strong predictor for the ability to perform two different working memory tasks simultaneously (after scanning). It explained 60% of the variation in information processing capacity across individuals. In contrast, the behavioural measures of automatization did not predict this. We postulate that automatization involves at least two partially independent neurophysiological mechanisms, i.e. (i) streamlining of neuronal communication which improves performance on a single task; and (ii) functional trimming of neuronal ensembles which enhances the capacity to accommodate processing of additional tasks, potentially by facilitating rapid switching of instruction sets or contexts. Finally, this study shows that fMRI can provide information that predicts behavioural output, which is not provided by overt behavioural measures. C1 Univ Med Ctr Utrecht, Dept Psychiat, Rudolf Magnus Inst Neurosci, Funct Neuroimaging Sect, NL-3584 CX Utrecht, Netherlands. NINDS, Lab Funct & Mol Imaging, Bethesda, MD 20892 USA. RP Ramsey, NF (reprint author), Univ Med Ctr Utrecht, Dept Psychiat, Rudolf Magnus Inst Neurosci, Funct Neuroimaging Sect, Room A-01-126,Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands. EM n.ramsey@azu.nl NR 37 TC 43 Z9 43 U1 1 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD MAR PY 2004 VL 127 BP 517 EP 525 DI 10.1093/brain/awh060 PN 3 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 801PW UT WOS:000220108800006 PM 14691061 ER PT J AU Pereira, MG Volchan, E Oliveira, L Machado-Pinheiro, W Rodrigues, JA Nepomuceno, FVP Pessoa, L AF Pereira, MG Volchan, E Oliveira, L Machado-Pinheiro, W Rodrigues, JA Nepomuceno, FVP Pessoa, L TI Behavioral modulation by mutilation pictures in women SO BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH LA English DT Article DE emotion; behavior; reaction time; sex differences; affective stimulus ID AUTOMATIC EVALUATION; SEX-DIFFERENCES; VISUAL-CORTEX; ATTENTION; ACTIVATION; STIMULI; EMOTION; TIME AB Previous studies have shown that women are more emotionally expressive than men. It is unclear, however, if women are also more susceptible to the emotional modulation of behavior imposed by an affective stimulus. To investigate this issue, we devised a task in which female subjects performed six sequential trials of visual target detection following the presentation of emotional (mutilation and erotic) or neutral pictures (domestic utensils and objects) and compared the data obtained in the present study with those described in a previous study with male subjects. The experiment consisted of three blocks of 24 pictures and each block had an approximate duration of 4 min. Our sample consisted of 36 subjects (age range: 18 to 26 years) and each subject performed all blocks. Trials following the presentation of mutilation pictures (283 ms) had significantly slower reaction times than those following neutral (270 ms) pictures. None of the trials in the "pleasant block"(271 ms) was significantly different from those in the "neutral block". The increase in reaction time observed in the unpleasant block may be related in part to the activation of motivational systems leading to an avoidance behavior. The interference effect observed in this study was similar to the pattern previously described for men. Thus, although women may be more emotionally expressive, they were not more reactive to aversive stimuli than men, as measured by emotional interference in a simple reaction time task. C1 Univ Fed Rio de Janeiro, Dept Neurobiol, Inst Biofis, Rio De Janeiro, RJ, Brazil. Univ Fed Fluminense, Dept Fisiol & Farmacol, Niteroi, RJ, Brazil. NIMH, Bethesda, MD 20892 USA. RP Pereira, MG (reprint author), Univ Fed Rio de Janeiro, Dept Neurobiol, Inst Biofis, Rio De Janeiro, RJ, Brazil. EM mfortes@biof.ufrj.br RI Volchan, Eliane/C-5792-2013 NR 38 TC 13 Z9 15 U1 3 U2 4 PU ASSOC BRAS DIVULG CIENTIFICA PI SAO PAULO PA FACULDADE MEDICINA, SALA 21, 14049 RIBEIRAO PRETO, SAO PAULO, BRAZIL SN 0100-879X J9 BRAZ J MED BIOL RES JI Brazilian J. Med. Biol. Res. PD MAR PY 2004 VL 37 IS 3 BP 353 EP 362 DI 10.1590/S0100-879X2004000300011 PG 10 WC Biology; Medicine, Research & Experimental SC Life Sciences & Biomedicine - Other Topics; Research & Experimental Medicine GA 805MY UT WOS:000220371600011 PM 15060703 ER PT J AU Srinivasan, R Chakrabarti, S Walsh, T Igarashi, T Takahashi, Y Kleiner, D Donohue, T Shalabi, R Carvallo, C Barrett, AJ Geller, N Childs, R AF Srinivasan, R Chakrabarti, S Walsh, T Igarashi, T Takahashi, Y Kleiner, D Donohue, T Shalabi, R Carvallo, C Barrett, AJ Geller, N Childs, R TI Improved survival in steroid-refractory acute graft versus host disease after non-myeloablative allogeneic transplantation using a daclizumab-based strategy with comprehensive infection prophylaxis SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE acute graft versus host disease; steroid-refractory; allogeneic transplant; infliximab; daclizumab ID STEM-CELL TRANSPLANTATION; BONE-MARROW-TRANSPLANTATION; ANTI-THYMOCYTE GLOBULIN; RESISTANT ACUTE; ANTITHYMOCYTE GLOBULIN; RETROSPECTIVE ANALYSIS; FUNGAL-INFECTIONS; ALPHA ANTIBODY; RISK-FACTORS; THERAPY AB Approximately 15% of patients undergoing non-myeloablative allogeneic haematopoietical cell transplantation (NMHCT) develop steroid-refractory acute-graft versus host disease (aGVHD), a usually fatal complication. We encountered 18 cases of steroid-refractory aGVHD in 146 patients, undergoing NMHCT from a related human leucocyte antigen-compatible donor following cyclophosphamide/fludarabine-based conditioning. Our initial cohort of steroid-refractory aGVHD patients treated with antithymocyte globulin (ATG) and mycophenolate mofetil (regimen-1: n = 6) had high GVHD-related mortality. Therefore, we investigated an alternative strategy for subsequent patients developing this complication (regimen-2: n = 12), consisting of daclizumab (alone or combined with infliximab/ATG) and targeted broad spectrum antibacterial and aspergillus prophylaxis in conjunction with rapid tapering of steroids to minimize opportunistic infections. In a retrospective analysis, patients receiving regimen-2 were significantly more likely to have complete resolution of GVHD compared with those receiving regimen-1 [12/12 (100%) vs. 1/6 (17%); P < 0.001]. When compared with those receiving regimen-1, regimen-2 patients also had a higher probability of survival at day 100 (100% vs. 50%) and day 200 (73% vs. 17%) post-transplant, and improved overall survival (median 453 d vs. 42 d from aGVHD onset; P < 0.0001). GVHD-related mortality was 89% for regimen-1 patients vs. 17% for regimen-2 patients (P < 0.0001). These data suggest that a co-ordinated approach using immunoregulatory monoclonal antibodies, pre-emptive antimicrobial therapy and judicious steroid withdrawal can dramatically improve outcome in steroid-refractory aGVHD. C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. NCI, Pathol Lab, Bethesda, MD 20892 USA. NIH, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. RP Childs, R (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10,Rm 7C103,MSC1652,9000 Rockville Pike, Bethesda, MD 20892 USA. EM childsr@nih.gov RI Takahashi, Yoshiyuki/I-1929-2012; OI Kleiner, David/0000-0003-3442-4453 NR 50 TC 58 Z9 61 U1 0 U2 2 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD MAR PY 2004 VL 124 IS 6 BP 777 EP 786 DI 10.1111/j.1365-2141.2004.04856.x PG 10 WC Hematology SC Hematology GA 779KR UT WOS:000189294500010 PM 15009066 ER PT J AU Freeman, HP AF Freeman, HP TI Poverty, culture, and social injustice determinants of cancer disparities SO CA-A CANCER JOURNAL FOR CLINICIANS LA English DT Editorial Material ID RACIAL-DIFFERENCES; LUNG-CANCER C1 NCI, Ctr Reduce Canc Hlth Disparities, Rockville, MD USA. RP Freeman, HP (reprint author), NCI, Ctr Reduce Canc Hlth Disparities, Rockville, MD USA. NR 16 TC 118 Z9 122 U1 4 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0007-9235 J9 CA-CANCER J CLIN JI CA-Cancer J. Clin. PD MAR-APR PY 2004 VL 54 IS 2 BP 72 EP 77 PG 6 WC Oncology SC Oncology GA 958XZ UT WOS:000231482800004 PM 15061597 ER PT J AU Ward, E Jemal, A Cokkinides, V Singh, GK Cardinez, C Ghafoor, A Thun, M AF Ward, E Jemal, A Cokkinides, V Singh, GK Cardinez, C Ghafoor, A Thun, M TI Cancer disparities by race/ethnicity and socioeconomic status SO CA-A CANCER JOURNAL FOR CLINICIANS LA English DT Article ID OF-LIFE CARE; AFRICAN-AMERICAN; US; MORTALITY; WOMEN; OLDER; END; INFECTION; OUTCOMES; SOCIETY AB This article highlights disparities in cancer incidence, mortality, and relation to race/ethnicity, and census data on poverty in the county or census tract of The incidence and survival data derive from the National Cancer Institute's (NCI) Epidemiology, and End Results (SEER) Program; mortality data are from the National Health Statistics (NCHS); data on the prevalence of major cancer risk factors and screening are from the National Health Interview Survey (NHIS) conducted by NCHS. cancer sites combined, residents of poorer counties (those with greater than or equal to the population below the poverty line) have 13% higher death rates from cancer in men higher rates in women compared with more affluent counties (less than 10% below the line). Differences in cancer survival account for part of this disparity. Among both men women, five-year survival for all cancers combined is 10 percentage points lower persons who live in poorer than in more affluent census tracts. Even when census tract rate is accounted for, however, African American, American Indian/Alaskan Native, and Pacific Islander men and African American and American Indian/Alaskan Native women lower five-year survival than non-Hispanic Whites. More detailed analyses of selected show large variations in cancer survival by race and ethnicity. Opportunities to reduce disparities exist in prevention (reductions in tobacco use, physical inactivity, and obesity), detection (mammography, colorectal screening, Pap tests), treatment, and palliative care. C1 Amer Canc Soc, Dept Epidemiol & Surveillance Res, Atlanta, GA 30329 USA. Amer Canc Soc, Dept Epidemiol & Surveillance Res, Atlanta, GA 30329 USA. NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Ward, E (reprint author), Amer Canc Soc, Dept Epidemiol & Surveillance Res, Atlanta, GA 30329 USA. NR 49 TC 700 Z9 709 U1 12 U2 64 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0007-9235 J9 CA-CANCER J CLIN JI CA-Cancer J. Clin. PD MAR-APR PY 2004 VL 54 IS 2 BP 78 EP 93 PG 16 WC Oncology SC Oncology GA 958XZ UT WOS:000231482800005 PM 15061598 ER PT J AU Shabat, S Nyska, A Long, PH Goelman, G Abramovitch, R Ezov, N Levin-Harrus, T Peddada, S Redlich, M Yedgar, S Nyska, M AF Shabat, S Nyska, A Long, PH Goelman, G Abramovitch, R Ezov, N Levin-Harrus, T Peddada, S Redlich, M Yedgar, S Nyska, M TI Osteonecrosis in a chemically induced rat model of human hemolytic disorders associated with thrombosis - A new model for avascular necrosis of bone SO CALCIFIED TISSUE INTERNATIONAL LA English DT Article DE rat; thrombosis; 2-butoxyethanol; osteonecrosis; MRI ID SICKLE-CELL-DISEASE; FEMALE F344 RATS; MONOBUTYL ETHER 2-BUTOXYETHANOL; BETA-THALASSEMIA MAJOR; GROWTH-PLATE; HYPERCOAGULABLE STATE; INHALATION EXPOSURE; HISTOLOGIC-FINDINGS; FEMORAL-HEAD; INFARCTION AB Bone injury occurs in human hemolytic disorders associated with thrombosis, such as betathalassemia and sickle cell disease. Exposure of rats to 2-butoxyethanol (BE) has been associated with hemolytic anemia, disseminated thrombosis, and infarction in multiple organs including bone. This rat model apparently mimics acute hemolysis and thrombosis in humans. To elucidate the extent of bone injury, male and female Fischer F344 rats were given 4 daily doses of 250 mg BE/5 ml water/kg of body weight. Tail vertebrae were studied by histopathology and magnetic resonance imaging (MRI). Thrombosis and infarction were seen in both sexes, but females were more severely affected. Lesions were characterized by extensive medullary fat necrosis, granulomatous inflammation, fibroplasia, growth plate degeneration, and new woven bone formation adjacent to necrotic bone trabeculae. MRI mean and standard deviation tissue-density data for both sexes indicated a significant (P less than or equal to 0.05) decrease following 4-days treatment and a significant increase (P less than or equal to 0.05) following an additional 24 days without treatment. Thus, MRI was useful in revealing BE-induced bone injury, which was predominantly necrotic initially and subsequently regenerative with proliferation of connective tissue and bone following postischemia recovery. C1 Sapir Med Ctr, Dept Orthopaed Surg, IL-44281 Kefar Sava, Israel. NIEHS, Lab Expt Pathol, Res Triangle Pk, NC 27709 USA. Charles River Co, Pathol Associates, W Chester, OH 45069 USA. Hadassah Hebrew Univ Hosp, Dept Biophys & Nucl Med, Human Biol Res Ctr, MRI Lab, IL-91120 Jerusalem, Israel. Harlan Biotech Israel Ltd, IL-76326 Rehovot, Israel. NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. Hebrew Univ Jerusalem, Fac Med Dent, Dept Orthodont, IL-91120 Jerusalem, Israel. Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Biochem, IL-91120 Jerusalem, Israel. RP Shabat, S (reprint author), Sapir Med Ctr, Dept Orthopaed Surg, 48 Tchernichovsky St, IL-44281 Kefar Sava, Israel. EM drshabat@hotmail.com RI Peddada, Shyamal/D-1278-2012 NR 51 TC 11 Z9 13 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0171-967X J9 CALCIFIED TISSUE INT JI Calcif. Tissue Int. PD MAR PY 2004 VL 74 IS 3 BP 220 EP 228 DI 10.1007/s00223-003-0068-7 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 803TF UT WOS:000220252700001 PM 14517720 ER PT J AU Wang, SS Sherman, ME Hildesheim, A Lacey, JV Devesa, S AF Wang, SS Sherman, ME Hildesheim, A Lacey, JV Devesa, S TI Cervical adenocarcinoma and squamous cell carcinoma incidence trends among white women and black women in the United States for 1976-2000 SO CANCER LA English DT Article DE cervix; adenocarcinoma; squamous cell carcinoma; incidence; black; white; epidemiology ID CANCER SCREENING PRACTICES; ORAL-CONTRACEPTIVE USE; UTERINE CERVIX; IN-SITU; ADENOSQUAMOUS CARCINOMA; HUMAN-PAPILLOMAVIRUS; INCREASING INCIDENCE; INCIDENCE RATES; RISK-FACTORS; YOUNG-WOMEN AB BACKGROUND. Although cervical carcinoma incidence and mortality rates have declined in the U.S. greatly since the introduction of the Papanicolaou smear, this decline has not been uniform for all histologic subtypes. Therefore, the authors assessed the differential incidence rates of squamous cell carcinoma (SCC) and adenocarcinoma (AC) of the cervix by race and disease stage for the past 25 years. METHODS. Data from nine population-based cancer registries participating in the U.S. Surveillance, Epidemiology, and End Results (SEER) Program were used to compute incidence rates for cervical carcinoma diagnosed during 1976-2000 by histologic subtype (SCC and AC), race (black and white), age, and disease stage (in situ, localized, regional, or distant). RESULTS. in black women and white women, the overall incidence of invasive SCC declined over time, and the majority of tumors that are detected currently are in situ and localized carcinomas in young women. The incidence of in situ SCC increased sharply in the early 1990s. AC in situ (AIS) incidence rates increased, especially among young women. In black women, invasive AC incidence rose linearly with age. CONCLUSIONS. Changes in screening, endocervical sampling, nomenclature, and improvements in treatment likely explain the increased in situ cervical SCC incidence in white women and black women. Increasing AIS incidence over the past 20 years in white women has not yet translated into a decrease in invasive AC incidence. Etiologic factors may explain the rising invasive cervical AC incidence in young white women; rising cervical AC incidence with age in black women may reflect either lack of effective screening or a differential disease etiology. (C) 2004 American Cancer Society. C1 NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Wang, SS (reprint author), NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS MSC 7234, Bethesda, MD 20892 USA. EM wangso@mail.nih.gov NR 60 TC 204 Z9 224 U1 0 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD MAR 1 PY 2004 VL 100 IS 5 BP 1035 EP 1044 DI 10.1002/cncr.20064 PG 10 WC Oncology SC Oncology GA 775XB UT WOS:000189085000021 PM 14983500 ER PT J AU Sherman, ME Mink, PJ Curtis, R Cote, TR Brooks, S Hartge, P Devesa, S AF Sherman, ME Mink, PJ Curtis, R Cote, TR Brooks, S Hartge, P Devesa, S TI Survival among women with borderline ovarian tumors and ovarian carcinoma - A population-based analysis SO CANCER LA English DT Article DE ovary; neoplasia; borderline; low malignant potential; survival; serous; mucinous ID MICROPAPILLARY SEROUS CARCINOMA; K-RAS MUTATIONS; PSEUDOMYXOMA-PERITONEI; CIGARETTE-SMOKING; MUCINOUS TUMORS; RISK-FACTORS; CLINICOPATHOLOGICAL ANALYSIS; HISTOLOGIC TYPE; INTESTINAL-TYPE; UNITED-STATES AB BACKGROUND. Serous and mucinous ovarian tumors of low malignant potential (LMP-S and LMP-M, respectively) are noninvasive tumors that portend excellent survival when confined to the ovary. Comparison of the survival for women with LMP tumors staged as distant with women who have carcinoma may have important implications for diagnostic terminology and clinical management. METHODS. The authors compared relative survival rates among patients diagnosed with ovarian tumors during the period 1988-1999 (with follow-up through 2000) by histologic type, disease stage, tumor grade (for carcinomas), and patient age, using data from the Surveillance, Epidemiology, and End Results Program. RESULTS. The overall relative survival rate at 10 years (+/- 1.96 standard errors) was 96.9% +/- 2.3% for women with LMP-S tumors, 30.4% +/- 1.7% for women with serous carcinoma (CA-S); 94.0% +/- 3.1% for women with LMP-M tumors, and 64.7% +/- 3.4% for women with mucinous carcinoma (CA-M). The survival rate at 10 years for women with distant-stage LMP-S tumors was 89.9% +/- 5.3%, compared with 96.1% +/- 8.6% for women with well differentiated, localized CA-S. The survival rate for women with distant-stage LMP-M tumors at 5 years was 85.5% +/- 9.0%, compared with 95.5% +/- 3.4% for women with well differentiated, localized CA-M (data for 10 years were limited). Mucinous ovarian neoplasms were associated with all excess of second malignancies of the digestive tract. CONCLUSIONS. Relative survival among women with distant-stage LMP tumors was not 100% and resembled the survival of women who had carcinoma exhibiting favorable prognostic features (localized stage). Future studies of women with high-stage LMP tumors are required to clarify the pathogenesis of extraovarian lesions and their implications for management and prognosis. Published 2004 by the American Cancer Society.* C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Exponent, Washington, DC USA. US FDA, Therapeut & Blood Safety Branch, Rockville, MD 20857 USA. Univ Maryland, Sch Med, Dept Obstet & Gynecol, Baltimore, MD 21201 USA. RP Sherman, ME (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Room 7080, Bethesda, MD 20892 USA. EM shermanm@mail.nih.gov NR 47 TC 78 Z9 82 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD MAR 1 PY 2004 VL 100 IS 5 BP 1045 EP 1052 DI 10.1002/cncr.20080 PG 8 WC Oncology SC Oncology GA 775XB UT WOS:000189085000022 PM 14983501 ER PT J AU Camphausen, K Tofilon, PJ AF Camphausen, K Tofilon, PJ TI Combining radiation and molecular targeting in cancer therapy SO CANCER BIOLOGY & THERAPY LA English DT Review DE molecular targets; radiotherapy; HSP90; Ras; EGFR ID SQUAMOUS-CELL CARCINOMAS; MAMMARY-CARCINOMA; TUMOR RESISTANCE; EGR-1 PROMOTER; RAS ONCOGENES; RECEPTOR; RADIOSENSITIZATION; RADIOTHERAPY; EXPRESSION; GENE AB Radiotherapy continues to remain a major treatment modality for solid tumors. However, advances in fundamental radiobiology suggest that improvements in tumor control can be achieved through strategies that combine radiation and molecular targeting. One approach is to target a specific molecule involved in tumor cell survival after irradiation, which is currently being clinically evaluated using inhibitors of EGFR or Ras. Because of tumor heterogeneity and the existence of multiple tumor radio-resistance pathways, an extension of this approach being investigated at the pre-clinical level is to use Hsp90 inhibitors as a means of reducing the levels of multiple radioresponse regulatory proteins. In addition, it may also be possible to target normal tissue processes, such as angiogenesis, to enhance the radioresponse of tumors. Finally, an alternative approach to combining radiation and molecular targeting is to exploit radiation-induced gene expression to induce targets for other modalities or to increase their effectiveness. C1 NCI, Radiat Oncol Branch, Imaging & Mol Therapeut Sect, Bethesda, MD 20892 USA. NCI, Mol Radiat Therapeut Branch, Bethesda, MD 20892 USA. RP Camphausen, K (reprint author), NCI, Radiat Oncol Branch, Imaging & Mol Therapeut Sect, 10 Ctr Dr,Bldg 10,Room B3B69, Bethesda, MD 20892 USA. EM camphauk@mail.nih.gov NR 44 TC 32 Z9 32 U1 0 U2 0 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD MAR PY 2004 VL 3 IS 3 BP 247 EP 250 PG 4 WC Oncology SC Oncology GA 840ZN UT WOS:000222899200001 PM 15107611 ER PT J AU Glick, AB AF Glick, AB TI TGF beta 1, back to the future - Revisiting its role as a transforming growth factor SO CANCER BIOLOGY & THERAPY LA English DT Review DE TGF beta 1; tumor progression; metastasis; mouse models; neovascularization; EMT ID BREAST-CANCER CELLS; EPITHELIAL-MESENCHYMAL TRANSITION; FACTOR-BETA; TGF-BETA; DISEASE PROGRESSION; TUMOR PROGRESSION; PROSTATE-CANCER; IN-VIVO; FUNCTIONAL-CHARACTERIZATION; COLORECTAL-CANCER AB TGFbeta1 was initially identified in culture media from transformed cells as part of a factor that could produce a transformed phenotype in a nontransformed cell line. Subsequently this activity was separated into TGFbeta and TGFalpha, an EGF receptor ligand. With the discovery that TGFbeta1 was a potent growth inhibitor of epithelial cells, and the identification of inactivating mutations within the TGFbeta1 signaling pathway in cancers it became clear that TGFbeta1 signaling is a tumor suppressor pathway for early stages of cancer. However many human carcinomas overexpress TGFbeta1 and this is associated with poor patient prognosis and increased frequency of metastasis. Similar results have been obtained with tumor cell lines and experimental animal models. Thus stage specific duality of function is the emerging paradigm for the role of TGFbeta1 in cancer. This review will focus on the evidence for TGFbeta1 as a tumor promoting and metastasis factor and examine the biological and molecular basis for these effects. It is proposed that the switch from tumor suppressor to oncogene reflects genetic or epigenetic alterations in signaling pathways in tumor cells that alter the readout from the TGFbeta1 pathway. C1 NCI, Cellular Carcinogenesis & Tumor Promot Lab, Canc Res Ctr, Bethesda, MD 20289 USA. RP Glick, AB (reprint author), NCI, Cellular Carcinogenesis & Tumor Promot Lab, Canc Res Ctr, Bld 37,Room 4060C, Bethesda, MD 20289 USA. EM glicka@dc37a.nci.nih.gov NR 92 TC 43 Z9 49 U1 0 U2 4 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD MAR PY 2004 VL 3 IS 3 BP 276 EP 283 DI 10.4161/cbt.3.3.849 PG 8 WC Oncology SC Oncology GA 840ZN UT WOS:000222899200005 PM 15034302 ER PT J AU Singh, A Figg, WD AF Singh, A Figg, WD TI Upregulation of the androgen receptor during prostate cancer progression SO CANCER BIOLOGY & THERAPY LA English DT Article DE androgen receptor; prostate; cancer; resistance; microarray ID FAILURE; THERAPY; GENE AB The androgen receptor is one of the central factors in mediating prostate cancer progression and is an important target for treatment. Several possible mechanisms have been put forth as to how it promotes this process. In the January 2004 issue of Nature Medicine, Chen et al. report that the androgen receptor is consistently upregulated as hormone sensitive prostate cancer changes to a hormone refractory state. They also show that this change is intricately involved during the development of resistance to androgen ablation therapy. C1 NCI, Canc Therapeut Branch, Canc Res Ctr, Bethesda, MD 20892 USA. Howard Hughes Med Inst, Chevy Chase, MD USA. RP Figg, WD (reprint author), NCI, Canc Therapeut Branch, Canc Res Ctr, Bldg 10,Room 5A01 MSC 1910,9000 Rockville Pike, Bethesda, MD 20892 USA. EM wdfigg@helix.nih.gov RI Figg Sr, William/M-2411-2016 NR 11 TC 1 Z9 1 U1 0 U2 0 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD MAR PY 2004 VL 3 IS 3 BP 284 EP 285 DI 10.4161/cbt.3.3.785 PG 2 WC Oncology SC Oncology GA 840ZN UT WOS:000222899200006 PM 14764990 ER PT J AU LeRoith, D Helman, L AF LeRoith, D Helman, L TI The new kid on the block(ade) of the IGF-1 receptor SO CANCER CELL LA English DT Article ID GROWTH-FACTOR-I; TRANSFORMATION; FIBROBLASTS; CANCER; TUMOR; GENE AB The insulin-like growth factors (IGF) system, and particularly the IGF-1 receptor, has recently become the subject of major interest in the arena of cancer research. Its involvement in cancer cell growth and survival makes the system an excellent target as potential adjunct therapy to standard chemotherapy. C1 NIDDK, Diabet Branch, Pediat Oncol Branch, NCI, Bethesda, MD 20892 USA. RP LeRoith, D (reprint author), NIDDK, Diabet Branch, Pediat Oncol Branch, NCI, Bethesda, MD 20892 USA. EM derek@helix.nih.gov NR 10 TC 65 Z9 69 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD MAR PY 2004 VL 5 IS 3 BP 201 EP 202 DI 10.1016/S1535-6108(04)00054-6 PG 2 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 807UN UT WOS:000220526500001 PM 15050909 ER PT J AU Crawford, YG Gauthier, ML Joubel, A Mantei, K Kozakiewicz, K Afshari, CA Tlsty, TD AF Crawford, YG Gauthier, ML Joubel, A Mantei, K Kozakiewicz, K Afshari, CA Tlsty, TD TI Histologically normal human mammary epithelia with silenced p16(INK4a) overexpress COX-2, promoting a premalignant program SO CANCER CELL LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; SELECTIVE CYCLOOXYGENASE-2 INHIBITOR; BREAST-CANCER; UP-REGULATION; ASPIRIN USE; CELLS; EXPRESSION; SENESCENCE; APOPTOSIS; GROWTH AB Breast tissue from healthy women contains variant mammary epithelial cells (vHMEC) exhibiting p16(INK4a) promoter hypermethylation both in vivo and in vitro. When continuously cultured, vHMEC acquire telomeric dysfunction and produce the types of chromosomal abnormalities seen in premalignant lesions of cancer. We find that late passage vHMEC express elevated prostaglandin cyclo-oxygenase 2 (COX-2), which contributes to increased prostaglandin synthesis, angiogenic activity, and invasive ability. These data demonstrate the existence of human mammary epithelial cells with the potential to acquire multiple genomic alterations and phenotypes associated with malignant cells. Moreover, COX-2 overexpression coincides with focal areas of p16(INK4a) hypermethylation in vivo, creating ideal candidates as precursors to breast cancer. These putative precursors can be selectively eliminated upon exposure to COX-2 inhibitors in vitro. C1 Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Ctr Comprehens Canc, San Francisco, CA 94143 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Tlsty, TD (reprint author), Univ Calif San Francisco, Dept Pathol, San Francisco, CA 94143 USA. EM ttlsty@itsa.ucsf.edu NR 41 TC 105 Z9 105 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD MAR PY 2004 VL 5 IS 3 BP 263 EP 273 DI 10.1016/S1535-6108(04)00023-6 PG 11 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 807UN UT WOS:000220526500010 PM 15050918 ER PT J AU Krouse, RS Rosenfeld, KE Grant, M Aziz, N Byock, I Sloan, J Casarett, D AF Krouse, RS Rosenfeld, KE Grant, M Aziz, N Byock, I Sloan, J Casarett, D TI Palliative care research: Issues and opportunities SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Editorial Material ID MALIGNANT BOWEL OBSTRUCTION; QUALITY-OF-LIFE; CANCER CARE; GUIDELINES C1 So Arizona Vet Affairs Hlth Care Syst, Dept Surg, Tucson, AZ 85723 USA. Univ Arizona, Tucson, AZ 85721 USA. W Los Angeles Vet Affairs Med Ctr, Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. City Hope Natl Med Ctr, Dept Nursing Res & Educ, Duarte, CA 91010 USA. NCI, Off Canc Survivorship, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Dartmouth Hitchcock Med Ctr, Sect Palliat Med, Hanover, NH USA. Mayo Canc Ctr, Stat Unit, Rochester, MN USA. Univ Penn, Ctr Hlth Equ Res & Promot, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Univ Penn, Div Geriatr, Philadelphia, PA 19104 USA. RP Krouse, RS (reprint author), So Arizona Vet Affairs Hlth Care Syst, Dept Surg, Surg Care Line 2-112, Tucson, AZ 85723 USA. EM robert.krouse@med.va.gov NR 17 TC 20 Z9 21 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAR PY 2004 VL 13 IS 3 BP 337 EP 339 PG 3 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 801FE UT WOS:000220081000001 PM 15006905 ER PT J AU Morton, LM Engels, EA Holford, TR Leaderer, B Zhang, YW Zahm, SH Boyle, P Zhang, B Flynn, S Tallini, G Owens, PH Zheng, TZ AF Morton, LM Engels, EA Holford, TR Leaderer, B Zhang, YW Zahm, SH Boyle, P Zhang, B Flynn, S Tallini, G Owens, PH Zheng, TZ TI Hepatitis C virus and risk of non-Hodgkin lymphoma: A population-based case-control study among Connecticut women SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID B-CELL LYMPHOMAS; LYMPHOPROLIFERATIVE DISORDERS; MIXED CRYOGLOBULINEMIA; MALIGNANT-CELLS; INFECTION; PREVALENCE; HCV; RECEPTOR; THERAPY AB Objective: Previous epidemiologic studies of hepatitis C virus (HCV) infection and B-cell non-Hodgkin lymphoma (B-NHL) have yielded conflicting results, perhaps due to differences in the classification of B-NHL and the choice of non-population-based control groups that may not reflect the background population prevalence of HCV. To further investigate the link between HCV and NHL, we conducted HCV testing on serum samples of 998 women (464 cases; 534 controls) from a population-based case-control study of women in Connecticut. Methods: Serum samples were screened for HCV antibodies using an enzyme immunoassay; positive samples were confirmed by additional testing for HCV antibodies and for serum HCV RNA. Results: Approximately 2% (8 of 464) of cases and 1% (5 of 534) of controls tested positive for HCV. The risk of NHL associated with HCV infection appeared to be concentrated among B-cell lymphomas [odds ratio (OR) 2.0; 95% confidence interval (CI) 0.6, 8.2], particularly among follicular lymphomas (OR 4.1, 95% CI 0.8, 19.4). Conclusion: The primary strength of this study is our use of a population-based study design, although the low prevalence of HCV among women in Connecticut resulted in wide CIs for the estimated association between HCV and B-NHL subtypes. Our study suggests that HCV may be associated with increased risk of development of B-NHL, and that this risk may vary by B-NHL subtype among women. Due to the relatively low prevalence of HCV in our study population and the scarcity of population-based epidemiologic research on this subject, our study highlights the need for additional large, population-based studies of the role of HCV in the etiology of B-NHL. C1 Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT USA. Yale Univ, Sch Med, Dept Pathol, New Haven, CT USA. European Inst Oncol, Dept Epidemiol & Biostat, Milan, Italy. NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD USA. McGill Univ, Dept Epidemiol & Biostat, Montreal, PQ, Canada. RP Zheng, TZ (reprint author), 129 Church St,Suite 700, New Haven, CT 06510 USA. EM tongzhang.zheng@yale.edu RI Boyle, Peter/A-4380-2014; Morton, Lindsay/B-5234-2015; OI Boyle, Peter/0000-0001-6251-0610; Morton, Lindsay/0000-0001-9767-2310; Tallini, Giovanni/0000-0003-0113-6682 FU NCI NIH HHS [CA62006-05] NR 50 TC 34 Z9 36 U1 1 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAR PY 2004 VL 13 IS 3 BP 425 EP 430 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 801FE UT WOS:000220081000015 PM 15006919 ER PT J AU Stolzenberg-Solomon, RZ Limburg, P Pollak, M Taylor, PR Virtamo, J Albanes, D AF Stolzenberg-Solomon, RZ Limburg, P Pollak, M Taylor, PR Virtamo, J Albanes, D TI Insulin-like growth factor (IGF)-1, IGF-binding protein-3, and pancreatic cancer in male smokers SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID FACTOR BINDING-PROTEIN-3 CONCENTRATIONS; FACTOR-I; TRIAL COHORT; SERUM; RISK; AUTOCRINE; MEN; DETERMINANTS; EXPRESSION; RECEPTOR AB To investigate whether insulin-like growth factor (IGF)-1 and IGF-binding protein-3 (IGFBP-3) are prospectively associated with exocrine pancreatic cancer, we conducted a nested case-control study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort of 29,133 male Finnish smokers, aged 50-69 years. To avoid the potential influence of subclinical cancer on IGF-1 And IGFBP-3, all subjects in this study were alive without clinical evidence of cancer during their 5th year of the cohort follow-up. Four hundred randomly selected cohort controls and 93 incident pancreatic adenocarcinoma cases that occurred between their 5th follow-up year through 1997 (i.e., up to 12.7 years of follow-up) were included in this study. Concentrations of IGF-1 and IGFBP-3 were measured in-serum samples obtained at baseline using ELISA. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression models, adjusted for confounders. Neither IGF-1, IGFBP-3, nor the IGF-1:IGFBP-3 molar ratio was significantly associated with pancreatic cancer: highest compared to lowest tertile, OR = 0.67, 95% CI 0.37-1.21, P trend = 0.17, OR = 0.70, 95% CI 0.38-1.27, P trend = 0.12; and OR = 0.85, 95% CI 0.50-1.46, P trend = 0.54, respectively. Our results do not support the hypothesis that serum IGF-1 and IGFBP-3 concentrations are associated with pancreatic cancer risk among male smokers. Further studies are necessary to evaluate these associations in other populations. C1 NCI, NIH, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Mayo Clin, Div Gastroenterol & Hepatol, Rochester, MN USA. Jewish Gen Hosp, Canc Prevent Program, Montreal, PQ, Canada. McGill Univ, Montreal, PQ, Canada. NCI, Div Clin Sci, Canc Prevent Studies Branch, Bethesda, MD USA. Natl Publ Hlth Inst, Dept Epidemiol & Hlth Promot, Helsinki, Finland. RP Stolzenberg-Solomon, RZ (reprint author), NCI, NIH, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Suite 320,EPS Room 7039,MSC 7232, Bethesda, MD 20892 USA. EM rs221z@nih.gov RI Pollak, Michael/G-9094-2011; Albanes, Demetrius/B-9749-2015 OI Pollak, Michael/0000-0003-3047-0604; FU CCR NIH HHS [N01-RC-45035]; NCI NIH HHS [N01-CN-45165] NR 33 TC 31 Z9 32 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAR PY 2004 VL 13 IS 3 BP 438 EP 444 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 801FE UT WOS:000220081000017 PM 15006921 ER PT J AU Habis, AH Vernon, SD Lee, DR Verma, M Unger, ER AF Habis, AH Vernon, SD Lee, DR Verma, M Unger, ER TI Molecular quality of exfoliated cervical cells: Implications for molecular epidemiology and biomarker discovery SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID SCATTERING SUBMICROSCOPIC PARTICLES; HIGHLY FLUORESCENT ANALOGS; POLYMERASE CHAIN-REACTION; BIOLOGICAL APPLICATIONS; TRACER LABELS; SAMPLES; RNA; TRANSCRIPTS AB The biologic sample collected in molecular epidemiology studies must accurately reflect the disease being studied and have sufficient molecular quality for the intended assays. Noninvasive sampling methods, such as scrapes or brushes, are increasingly used. In this study, we evaluate the impact of sample collection media and extraction methods on the quality and yield of RNA from routine exfoliated cervical cytology. Excess cellular material remaining on the cytologic collection device after preparation of the routine screening Papanicolaou smear was placed in a variety of collection media and extracted using two commercial kits. The collection media had the largest impact on the yield and quality of RNA as evaluated by denaturing agarose gel electrophoresis and image analysis. Two collection media, PAXgene and PreservCyt, yielded RNA from most samples. The RNA showed some degree of degradation as evidenced by the reduced size of the higher molecular weight ribosomal band. However, with a sensitive gold particle-based detection method, reproducible microarray results were obtained using this RNA. C1 US PHS, US Dept Hlth & Human Serv, Ctr Dis Control & Prevent, Atlanta, GA USA. NCI, Canc Biomarkers Res Grp, Bethesda, MD 20892 USA. RP Unger, ER (reprint author), Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Div Viral & Rickettsial Dis, Viral Exanthems & Herpesvirus Branch, 1600 Clifton Rd,Mailstop G-41, Atlanta, GA 30333 USA. EM eru0@cdc.gov OI Unger, Elizabeth/0000-0002-2925-5635 FU NCI NIH HHS [Y1-CN-0101-01] NR 13 TC 31 Z9 35 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAR PY 2004 VL 13 IS 3 BP 492 EP 496 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 801FE UT WOS:000220081000025 PM 15006929 ER PT J AU O'Brien, TR Kirk, G Zhang, MD AF O'Brien, TR Kirk, G Zhang, MD TI Hepatocellular carcinoma: Paradigm of preventive oncology SO CANCER JOURNAL LA English DT Article DE epidemiology; hepatitis B virus; hepatitis C virus; hepatocellular carcinoma; liver; oncology; prevention; public health; treatment; vaccine ID HEPATITIS-C VIRUS; B-VIRUS; UNITED-STATES; PROTEOMIC PATTERNS; ALPHA-FETOPROTEIN; NATURAL-HISTORY; VIRAL-HEPATITIS; NON-A; INFECTION; CANCER AB Morbidity and mortality from hepatocellular carcinoma (HCC), which is primarily caused by hepatitis B virus or hepatitis C virus, can be prevented. Public health interventions have eliminated transfusion transmission of these viruses and, in endemic countries with effective hepatitis B virus vaccination programs, have greatly reduced incident hepatitis B virus infections (and HCC) in children. Antiviral treatment can eliminate detectable hepatitis C virus in 50%-80% of chronically infected patients, presumably reducing their risk of cancer. HCC survival rates remain universally poor, but early detection and treatment in developed countries has improved survival in selected patients. Despite these advances, worldwide HCC rates remain high, and additional preventive efforts are needed. The most important opportunity is wider distribution of hepatitis B virus vaccine in endemic areas. Development of an HCV vaccine, improved antiviral therapies, and better methods for HCC detection would also help decrease morbidity and mortality from HCC. HCC prevention efforts provide a paradigm for preventive oncology in cancers of viral etiology. C1 NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept HHS, Rockville, MD 20852 USA. RP O'Brien, TR (reprint author), NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept HHS, 6120 Execut Blvd,Room 8016,MSC 7248, Rockville, MD 20852 USA. EM obrient@exchange.nih.gov NR 64 TC 10 Z9 11 U1 0 U2 0 PU JONES AND BARTLETT PUBLISHERS PI SUDBURY PA 40 TALL PINE DR, SUDBURY, MA 01776 USA SN 1528-9117 J9 CANCER J JI Cancer J. PD MAR-APR PY 2004 VL 10 IS 2 BP 67 EP 73 PG 7 WC Oncology SC Oncology GA 815FE UT WOS:000221027400002 PM 15130266 ER PT J AU Elaraj, DM Alexander, HR AF Elaraj, DM Alexander, HR TI Current role of hepatic artery infusion and isolated liver perfusion for the treatment of colorectal cancer liver metastases SO CANCER JOURNAL LA English DT Article DE neoplasm metastases; liver; colorectal neoplasms; perfusion; regional; isolation perfusion; hyperthermia ID PROSPECTIVE RANDOMIZED TRIAL; TUMOR-NECROSIS-FACTOR; PHARMACOLOGICAL EVALUATION; INTRAARTERIAL FLOXURIDINE; REGIONAL CHEMOTHERAPY; SURGICAL RESECTION; NATURAL-HISTORY; FOLINIC ACID; CARCINOMA; FLUOROURACIL AB There are many treatment options for patients with metastatic colorectal carcinoma confined to the liver. Surgical resection alone can result in significant prolongation of survival in patients with favorable prognostic factors. Randomized studies of hepatic artery infusion therapy after complete resection of liver metastases have demonstrated improvements in hepatic recurrence-free survival but no impact on overall survival. Randomized trials evaluating the treatment of unresectable disease with hepatic artery infusion therapy have demonstrated higher response rates (31%-50%) than those seen with systemic chemotherapy (8%-20%) but no survival benefit. Vascular isolation and perfusion of the liver with chemotherapy with or without biologic agents under hyperthermic conditions is another regional modality that has been explored for the treatment of unresectable colorectal cancer liver metastases. Large series report high partial response rates (68%-77%), with responses being achieved in patients with advanced tumor burden and in those who have disease progression through prior treatment of hepatic metastases. C1 NCI, Surg Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Alexander, HR (reprint author), NCI, Surg Branch, Canc Res Ctr, NIH, Bldg 10,Room 2B07,9000 Rockville Pike, Bethesda, MD 20892 USA. EM Richard_Alexander@nih.gov NR 42 TC 11 Z9 11 U1 0 U2 1 PU JONES AND BARTLETT PUBLISHERS PI SUDBURY PA 40 TALL PINE DR, SUDBURY, MA 01776 USA SN 1528-9117 J9 CANCER J JI Cancer J. PD MAR-APR PY 2004 VL 10 IS 2 BP 128 EP 138 DI 10.1097/00130404-200403000-00008 PG 11 WC Oncology SC Oncology GA 815FE UT WOS:000221027400008 PM 15130272 ER PT J AU Sharkey, MS Lizee, G Gonzales, MI Patel, S Topalian, SL AF Sharkey, MS Lizee, G Gonzales, MI Patel, S Topalian, SL TI CD4(+) T-cell recognition of mutated B-RAF in melanoma patients harboring the V599E mutation SO CANCER RESEARCH LA English DT Article ID BRAF MUTATIONS; PEPTIDES; ANTIGEN; CANCER AB The potential of antigen-directed cancer immunotherapy has not been fully realized, perhaps because many commonly targeted tumor associated proteins are not essential to maintaining the malignant cell phenotype. A constitutively activating mutation in the signaling molecule BRAF is expressed frequently in melanomas and may play an important role in the biology of this disease. A 29-mer B-Raf peptide incorporating the V599E mutation was used for in vitro stimulation of lymphocytes derived from melanoma patients, generating MHC class II-restricted CD4(+) T cells specific for this peptide as well as for melanoma cells expressing B-Raf V599E. Mutated B-Raf exemplifies targets that may be ideal for immunotherapy. C1 NCI, Surg Branch, NIH, Canc Res Ctr, Bethesda, MD 20892 USA. RP Topalian, SL (reprint author), NCI, Surg Branch, NIH, Canc Res Ctr, 10-2B47, Bethesda, MD 20892 USA. EM Suzanne_Topalian@nih.gov NR 16 TC 38 Z9 38 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAR 1 PY 2004 VL 64 IS 5 BP 1595 EP 1599 DI 10.1158/0008-5472.CAN-03-3231 PG 5 WC Oncology SC Oncology GA 780DY UT WOS:000189357800007 PM 14996715 ER PT J AU Wang, Y Zhang, ZQ Yan, Y Lemon, WJ LaRegina, M Morrison, C Lubet, R You, M AF Wang, Y Zhang, ZQ Yan, Y Lemon, WJ LaRegina, M Morrison, C Lubet, R You, M TI A chemically induced model for squamous cell carcinoma of the lung in mice: Histopathology and strain susceptibility SO CANCER RESEARCH LA English DT Article ID K-RAS ONCOGENE; LINKAGE DISEQUILIBRIUM; BRONCHIAL EPITHELIUM; CIGARETTE-SMOKING; CHARCOAL POWDER; CANCER; MOUSE; TUMORS; ACTIVATION; INDUCTION AB Lung cancer, primarily associated with tobacco use, is the leading cause of cancer morbidity and mortality in the United States. Squamous cell carcinoma (SCC) is one of the four major histological types of lung cancer. Although there are several established models for lung adenoma and adenocarcinomas, there is no well-established mouse model for lung SCC. We treated eight different inbred strains of mice with N-nitroso-tris-chloroethylurea by skin painting and found that this regimen induced lung SCCs in five strains of mouse (SWR/J, NIH Swiss, A/J, BALB/cJ, and FVB/J) but not in the others (AKR/J,129/svJ, and C57BL/6J). Mouse lung SCCs have similar histopathological features and keratin staining to human SCC. Moreover, a wide spectrum of abnormal lung squamous phenotypes including hyperplasia, metaplasia, carcinoma in situ, and invasive carcinoma, were observed. There are strain-specific differences in susceptibility to Lsec induction by N-nitroso-tris-chloroethylurea with NIH Swiss, A/J, and SWR/J mice developing scores of SCCs whereas the resistant strains AKR/J, 129/svJ, and C57BL/6J failed to develop any SCCs. FVB/J and BALB/cJ mice had an intermediate response. We conducted whole-genome linkage disequilibrium analysis in seven strains of mice, divided into three phenotype categories of susceptibility, using Fisher's exact test applied to 6,128 markers in publically available databases. Three markers were found significantly associated with susceptibility to SCC with the P < 0.05. They were D1Mit169, D3Mit178, and D18Mit91. Interestingly, none of these sites overlap with the major susceptibility loci associated with lung adenoma/adenocarcinoma development in mice. The mouse SCC described here is highly significant for preclinical studies of lung cancer chemopreventive agents because most human trials have been conducted against precancerous lesions for SCC. Furthermore, this model can be used in determining genetic modifiers that contribute to susceptibility or resistance to lung SCC development. C1 Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA. Washington Univ, Sch Med, Siteman Canc Ctr, St Louis, MO 63110 USA. Washington Univ, Sch Med, Div Comparat Med, St Louis, MO 63110 USA. Ohio State Univ, Ctr Comprehens Canc, Dept Pathol, Columbus, OH 43210 USA. NCI, Chemoprevent Agent Dev Res Grp, Rockville, MD USA. RP You, M (reprint author), Washington Univ, Sch Med, Dept Surg, 660 S Euclid Ave, St Louis, MO 63110 USA. EM youm@msnotes.wustl.edu FU NCI NIH HHS [N01CN25104, R01CA58554, R01CA96103] NR 39 TC 61 Z9 64 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAR 1 PY 2004 VL 64 IS 5 BP 1647 EP 1654 DI 10.1158/0008-5472.CAN-03-3273 PG 8 WC Oncology SC Oncology GA 780DY UT WOS:000189357800015 PM 14996723 ER PT J AU Sredni, B Weil, M Khomenok, G Lebenthal, I Teitz, S Mardor, Y Ram, Z Orenstein, A Kershenovich, A Michowiz, S Cohen, YI Rappaport, ZH Freidkin, I Albeck, M Longo, DL Kalechman, Y AF Sredni, B Weil, M Khomenok, G Lebenthal, I Teitz, S Mardor, Y Ram, Z Orenstein, A Kershenovich, A Michowiz, S Cohen, YI Rappaport, ZH Freidkin, I Albeck, M Longo, DL Kalechman, Y TI Ammonium trichloro(dioxoethylene-o,o ')tellurate (AS101) sensitizes tumors to chemotherapy by inhibiting the tumor interleukin 10 autocrine loop SO CANCER RESEARCH LA English DT Article ID COLON-CANCER PATIENTS; NON-HODGKINS-LYMPHOMA; IMMUNOMODULATOR AS101; T-CELLS; PROGNOSTIC-SIGNIFICANCE; SERUM INTERLEUKIN-10; SIGNAL TRANSDUCER; CYTOTOXIC DRUGS; MELANOMA-CELLS; GROWTH-FACTOR AB Cancer cells of different solid and hematopoietic tumors express growth factors in respective stages of tumor progression, which by autocrine and paracrine effects enable them to grow autonomously. Here we show that the murine B16 melanoma cell line and two human primary cultures of stomach adenocarcinoma and glioblastoma multiforme (GBM) constitutively secrete interleukin (IL)-10 in an autocrine/paracrine manner. This cytokine is essential for tumor cell proliferation because its neutralization decreases clonogenicity of malignant cells, whereas addition of recombinant IL-10 increases cell proliferation. The immunomodulator ammonium trichloro(dioxoethylene-o,o')tellurate (AS101) decreased cell proliferation by inhibiting IL-10. This activity was abrogated by exogenous addition of recombinant IL-10. IL-10 inhibition by AS101 results in dephosphorylation of Stat3, followed by reduced expression of Bcl-2. Moreover, these activities of AS101 are associated with sensitization of tumor cells to chemotherapeutic drugs, resulting in their increased apoptosis. More importantly, AS101 sensitizes the human aggressive GBM tumor to paclitaxel both in vitro and in vivo by virtue of IL-10 inhibition. AS101 sensitizes GBM cells to paclitaxel at concentrations that do not affect tumor cells. This sensitization can also be obtained by transfection of GBM cells with IL-10 antisense oligonucleotides. Sensitization of GBM tumors to paclitaxel (Taxol) in vivo was obtained by either AS101 or by implantation of antisense IL-10-transfected cells. The results indicate that the IL-10 autocrine/paracrine loop plays an important role in the resistance of certain tumors to chemotherapeutic drugs. Therefore, anti-IL-10 treatment modalities with compounds such as AS101, combined with chemotherapy, may be effective in the treatment of certain malignancies. C1 Bar Ilan Univ, Fac Life Sci, CAIR Inst, IL-52900 Ramat Gan, Israel. Asaf Hrofeh Med Ctr, Dept Surg, Zerifin, Israel. Shebe Med Ctr, Ctr Adv Technol, Tel Hashomer, Israel. Tel Aviv Med Ctr & Sch Med, Dept Neurosurg, IL-64239 Tel Aviv, Israel. Rabin Med Ctr, Petah Tiqwa, Israel. Schneider Childrens Med Ctr Israel, Inst Pediat Hematol Oncol, Petah Tiqwa, Israel. Natl Inst Aging, Ctr Gerontol Res, Baltimore, MD USA. RP Sredni, B (reprint author), Bar Ilan Univ, Fac Life Sci, CAIR Inst, IL-52900 Ramat Gan, Israel. EM srednib@mail.biu.ac.il NR 47 TC 62 Z9 71 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAR 1 PY 2004 VL 64 IS 5 BP 1843 EP 1852 DI 10.1158/0008-5472.CAN-03-3179 PG 10 WC Oncology SC Oncology GA 780DY UT WOS:000189357800040 PM 14996748 ER PT J AU Bottone, FG Martinez, JM Alston-Mills, B Eling, TE AF Bottone, FG Martinez, JM Alston-Mills, B Eling, TE TI Gene modulation by Cox-1 and Cox-2 specific inhibitors in human colorectal carcinoma cancer cells SO CARCINOGENESIS LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; FAMILIAL ADENOMATOUS POLYPOSIS; NSAID-ACTIVATED GENE; HUMAN COLON; CYCLOOXYGENASE INHIBITORS; SULINDAC SULFIDE; MURINE MODEL; RANDOMIZED-TRIAL; OVARIAN-CANCER; MIN MOUSE AB Cox-1 and Cox-2 specific inhibitors exert chemo-preventative activity. However, the exact mechanisms for this activity remain unclear. Increasing evidence suggests that non-steroidal anti-inflammatory drugs regulate gene expression, which may be responsible, in part, for this activity. In this study, human colorectal carcinoma HCT-116 cells were treated with the Cox-1 specific inhibitor SC-560 and the Cox-2 specific inhibitor SC-58125 to evaluate their ability to induce apoptosis, inhibit cell proliferation, inhibit growth on soft agar and modulate gene expression. The Cox-1 specific inhibitor, SC-560 significantly induced apoptosis and inhibited the growth of HCT-116 cells on soft agar, an in vitro assay for tumorigenicity. SC-58125 moderately induced apoptosis and inhibited growth on soft agar at higher concentrations than were required for SC-560. Previously, we reported that the potent chemo-preventative drug sulindac sulfide altered the expression of eight genes including several transcription factors that may be linked to this drug's chemo-preventative activity. HCT-116 cells were treated with various concentrations of SC-560 or SC-58125 and changes in the expression of these eight genes were determined by real-time reverse transcription- polymerase chain reaction. SC-560 modulated mRNA expression of the eight genes studied. In contrast, SC-58125 required similar to5-10-fold higher concentrations to achieve similar degrees of gene modulation in six of eight genes. Changes in protein expression by SC-560 also occurred for five of these genes with antibodies available (NAG-1, ATF3, C/EBPbeta, MAD2 and MSX1). In conclusion, this is the first report to suggest that like sulindac sulfide, the Cox-1 specific inhibitor SC-560 appears to elicit chemo-preventative activity by altering gene expression, while the chemo-preventative effects of SC-58125 are complex and probably work through these and other mechanisms, such as the inhibition of Cox-2. C1 NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Computat Biol & Risk Anal, NIH, Res Triangle Pk, NC 27709 USA. N Carolina State Univ, Dept Anim Sci, Raleigh, NC 27695 USA. RP Eling, TE (reprint author), NIEHS, Mol Carcinogenesis Lab, NIH, POB 12233,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM eling@niehs.nih.gov NR 49 TC 40 Z9 41 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD MAR PY 2004 VL 25 IS 3 BP 349 EP 357 DI 10.1093/carcin/bgh016 PG 9 WC Oncology SC Oncology GA 800WR UT WOS:000220058900007 PM 14633654 ER PT J AU Koonin, EV AF Koonin, EV TI A non-adaptationist perspective on evolution of genomic complexity or the continued dethroning of man SO CELL CYCLE LA English DT Article DE genomic complexity; entropy; genone evolution; introns; neutral evolution; population size reduction ID TRANSPOSABLE ELEMENTS; EUKARYOTIC EVOLUTION; INTRON POSITIONS; GENE LOSS; DIVERGENCE; ORIGIN AB A new, non-adaptationist theory of evolution of genomic complexity was recently proposed by Lynch and Conery.(1) This concept holds that increase in complexity seen in eukaryotic genomes is a 'syndrome' caused by increase in genome entropy, which is inevitably triggered by reduction of population size. Here, I discuss the definitions of genomic entropy and complexity and the evidence supporting the entropic theory of genome complexity evolution, including new observations on concordant gain and loss of genes and introns in eukaryotic genomes. I further consider the far-reaching biological and philosophical implications of this theory. 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, 8600 Rockville Pike,Bldg 38A, Bethesda, MD 20894 USA. EM koonin@ncbi.nlm.nih.gov NR 28 TC 23 Z9 23 U1 0 U2 1 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD MAR PY 2004 VL 3 IS 3 BP 280 EP 285 PG 6 WC Cell Biology SC Cell Biology GA 833TF UT WOS:000222361400016 PM 14726650 ER PT J AU Appierto, V Villani, MG Cavadini, E Lotan, R Vinson, C Formelli, F AF Appierto, V Villani, MG Cavadini, E Lotan, R Vinson, C Formelli, F TI Involvement of c-Fos in fenretinide-induced apoptosis in human ovarian carcinoma cells SO CELL DEATH AND DIFFERENTIATION LA English DT Article DE retinoids; fenretinide; c-Fos; AP-1; apoptosis ID RETINOID N-(4-HYDROXYPHENYL) RETINAMIDE; ACID RECEPTOR-BETA; GROWTH-INHIBITION; TOPICAL TREATMENT; UP-REGULATION; EXPRESSION; CANCER; INDUCTION; LINES; AP-1 AB Fenretinide (HPR), a synthetic retinoid that exhibits lower toxicity than other retinoids, has shown preventive and therapeutic activity against ovarian tumors. Although the growth inhibitory effects of HPR have been ascribed to its ability to induce apoptosis, little is known about the molecular mechanisms involved. Since the proto-oncogene c-Fos has been implicated in apoptosis induction, we analyzed its role in mediating HPR response in a human ovarian carcinoma cell line (A2780) sensitive to HPR apoptotic effect. In these cells, HPR treatment caused induction of c-Fos expression, whereas such an effect was not observed in cells made resistant to HPR-induced apoptosis (A2780/HPR). Moreover, in a panel of other human ovarian carcinoma cell lines, c-Fos inducibility and HPR sensitivity were closely associated. Ceramide, which is involved in HPR-induced apoptosis, was also involved in c-Fos induction because its upregulation by HPR was reduced by fumonisin B-1, a ceramide synthase inhibitor. The causal relationship between c-Fos induction and apoptosis was established by the finding of an increased apoptotic rate in cells overexpressing c-Fos. Similarly to that observed for c-Fos expression, HPR treatment increased c-Jun expression in HPR-sensitive but not in HPR-resistant cells, suggesting the involvement of the transcription factor activating protein 1 (AP-1) in HPR-induced apoptosis. In gene reporter experiments, HPR stimulated AP-1 transcriptional activity and potentiated the AP-1 activity induced by 12-tetradecanoylphorbol 13-acetate. Furthermore, inhibition of AP-1 DNA binding, by transfecting A2780 cells with a dominant-negative Fos gene, caused decreased sensitivity to HPR apoptotic effects. Overall, the results indicate that c-Fos plays a role in mediating HPR-induced growth inhibition and apoptosis in ovarian cancer cells and suggest that c-Fos regulates these processes as a member of the AP-1 transcription factor. C1 Ist Nazl Studio & Cura Tumori, Dept Expt Oncol, Chemoprevent Unit, Milan, Italy. Univ Texas, MD Anderson Canc Ctr, Dept Thorac & Head & Neck Med Oncol, Houston, TX 77030 USA. NIH, Lab Metab, Bethesda, MD 20892 USA. RP Appierto, V (reprint author), Ist Nazl Studio & Cura Tumori, Dept Expt Oncol, Chemoprevent Unit, Milan, Italy. EM valentina.appierto@istitutotumori.mi.it RI Appierto, Valentina/B-9325-2017 OI Appierto, Valentina/0000-0002-8726-6981 NR 48 TC 20 Z9 20 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1350-9047 J9 CELL DEATH DIFFER JI Cell Death Differ. PD MAR PY 2004 VL 11 IS 3 BP 270 EP 279 DI 10.1038/sj.cdd.4401349 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 774GR UT WOS:000188971900004 PM 14647238 ER PT J AU Stadtman, ER AF Stadtman, ER TI Sixty years of research: from soil science and the browning of dried apricots to the biochemistry of metabolism SO CELLULAR AND MOLECULAR LIFE SCIENCES LA English DT Biographical-Item C1 NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Stadtman, ER (reprint author), NHLBI, Biochem Lab, NIH, Bldg 50,Room 2140,50 South Dr,MSC-8012, Bethesda, MD 20892 USA. EM erstadtman@nih.gov NR 1 TC 1 Z9 1 U1 0 U2 4 PU BIRKHAUSER VERLAG AG PI BASEL PA VIADUKSTRASSE 40-44, PO BOX 133, CH-4010 BASEL, SWITZERLAND SN 1420-682X J9 CELL MOL LIFE SCI JI Cell. Mol. Life Sci. PD MAR PY 2004 VL 61 IS 6 BP 625 EP 628 DI 10.1007/s00018-003-3409-9 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 807JG UT WOS:000220497200001 PM 15052406 ER PT J AU Vuong, C Voyich, JM Fischer, ER Braughton, KR Whitney, AR DeLeo, FR Otto, M AF Vuong, C Voyich, JM Fischer, ER Braughton, KR Whitney, AR DeLeo, FR Otto, M TI Polysaccharide intercellular adhesin (PIA) protects Staphylococcus epidermidis against major components of the human innate immune system SO CELLULAR MICROBIOLOGY LA English DT Article ID GROUP-A STREPTOCOCCUS; ANTIMICROBIAL PEPTIDES; BACTERIAL BIOFILMS; MOLECULAR-BASIS; INFECTIONS; AUREUS; ADHESIN/HEMAGGLUTININ; PATHOGENESIS; RESISTANCE; DEFENSINS AB The skin commensal and opportunistic pathogen Staphylococcus epidermidis is the leading cause of nosocomial and biofilm-associated infections. Little is known about the mechanisms by which S. epidermidis protects itself against the innate human immune system during colonization and infection. We used scanning electron microscopy to demonstrate that the exopolysaccharide intercellular adhesin (PIA) resides in fibrous strands on the bacterial cell surface, and that lack of PIA production results in complete loss of the extracellular matrix material that has been suggested to mediate immune evasion. Phagocytosis and killing by human polymorphonuclear leucocytes was significantly increased in a mutant strain lacking PIA production compared with the wild-type strain. The mutant strain was also significantly more susceptible to killing by major antibacterial peptides of human skin, cationic human beta-defensin 3 and LL-37, and anionic dermcidin. PIA represents the first defined factor of the staphylococcal biofilm matrix that protects against major components of human innate host defence. C1 NIAID, Lab Human Bacterial Pathogenesis, NIH, Rocky Mt Labs, Hamilton, MT 59840 USA. NIAID, Intracellular Parasites Lab, NIH, Rocky Mt Labs, Hamilton, MT 59840 USA. RP Otto, M (reprint author), NIAID, Lab Human Bacterial Pathogenesis, NIH, Rocky Mt Labs, 903 S 4th St, Hamilton, MT 59840 USA. EM motto@niaid.nih.gov OI DeLeo, Frank/0000-0003-3150-2516; Otto, Michael/0000-0002-2222-4115 NR 26 TC 284 Z9 305 U1 10 U2 33 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 1462-5814 J9 CELL MICROBIOL JI Cell Microbiol. PD MAR PY 2004 VL 6 IS 3 BP 269 EP 275 DI 10.1111/j.1462-5822.2004.00367.x PG 7 WC Cell Biology; Microbiology SC Cell Biology; Microbiology GA 771XK UT WOS:000188811200007 PM 14764110 ER PT J AU Blaizot, X Martinez-Marcos, A Arroyo-Jimenez, MD Marcos, P Artacho-Perula, E Munoz, M Chavoix, C Insausti, R AF Blaizot, X Martinez-Marcos, A Arroyo-Jimenez, MD Marcos, P Artacho-Perula, E Munoz, M Chavoix, C Insausti, R TI The parahippocampal gyrus in the baboon: Anatomical, cytoarchitectonic and magnetic resonance imaging (MRI) studies SO CEREBRAL CORTEX LA English DT Article DE entorhinal; functional neuroanatomy; magnetic resonance imaging; memory; monkey; perirhinal; posterior parahippocampal; temporal pole ID POSITRON-EMISSION-TOMOGRAPHY; VISUAL RECOGNITION MEMORY; MEDIAL TEMPORAL-LOBES; ENTORHINAL CORTEX; ALZHEIMERS-DISEASE; RHINAL CORTEX; HIPPOCAMPAL-FORMATION; HUMAN-BRAIN; UNANESTHETIZED MONKEYS; CORTICAL PROJECTIONS AB The parahippocampal gyrus, located at the medial temporal lobe, is a key structure in declarative memory processing. We have analyzed the general organization of the parahippocampal gyrus in the baboon, a nonhuman primate species relatively close to human. This region is rostrocaudally made up of the temporopolar, perirhinal, entorhinal (divided into seven subfields) and posterior parahippocampal (areas TH and TF) cortices. The basic analysis has been performed in three brains, serially sectioned and stained with thionin, myelin stain, acetylcholinesterase and parvalbumin, to determine cytoarchitectonic boundaries. Borders of all subfields were charted onto camera lucida drawings, and two-dimensional maps of the surface and topography of the parahippocampal gyrus were made. Finally, the limits of each parahippocampal area were then transposed on corresponding MR images (commonly used for in vivo PET or functional MRI activation studies) of two animals for precise identification. The general cytoarchitectonic features of the baboon parahippocampal gyrus are similar to macaques, but the size of temporopolar cortex and the laminar organization of perirhinal and posterior parahippocampal cortices resemble humans more than macaque species. In conclusion, the size and structure of the baboon parahippocampal cortex makes this species very appropriate for experimental studies on memory function. C1 Univ Castilla La Mancha, Dept Hlth Sci, Sch Med, Lab Human Neuroanat, Albacete 02071, Spain. CRIB, Albacete, Spain. NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA. Univ Basse Normandie, CHU Caen, Caen, France. RP Insausti, R (reprint author), Univ Castilla La Mancha, Dept Hlth Sci, Sch Med, Lab Human Neuroanat, Ave Almansa S-N, Albacete 02071, Spain. EM ricardo.insausti@uclm.es RI Munoz, Monica/C-9189-2009; MARTINEZ-MARCOS, ALINO/L-5127-2014; chavoix, chantal/O-1125-2015; OI MARTINEZ-MARCOS, ALINO/0000-0003-3691-3605; Munoz Lopez, Monica/0000-0002-5530-2394 NR 64 TC 14 Z9 14 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD MAR PY 2004 VL 14 IS 3 BP 231 EP 246 DI 10.1093/cercor/bhg123 PG 16 WC Neurosciences SC Neurosciences & Neurology GA 771NB UT WOS:000188791300001 PM 14754864 ER PT J AU Jiang, GH Jankowiak, R Grubor, N Banasiewicz, M Small, GJ Skorvaga, M Van Houten, B States, JC AF Jiang, GH Jankowiak, R Grubor, N Banasiewicz, M Small, GJ Skorvaga, M Van Houten, B States, JC TI Supercoiled DNA promotes formation of intercalated cis-N-2-deoxyguanine adducts and base-stacked trans-N-2-deoxyguanine adducts by (+)-7R,8S-dihydrodiol-9S,10R-epoxy-7,8,9,10-tetra-hydrobenzo[a]pyrene SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID NUCLEOTIDE EXCISION-REPAIR; POLYACRYLAMIDE-GEL ELECTROPHORESIS; P-32 POSTLABELING ASSAY; DIOL-EPOXIDE; ESCHERICHIA-COLI; ANTI-BENZOPYRENE DIOLEPOXIDE; I SENSITIVITY; SMOKERS LUNG; BENZOPYRENE; CONFORMATION AB The highly reactive and mutagenic benzo[a]pyrene metabolite, (+)-7R,8S-dihydroxy-9S,10R-epoxy- 7,8,9, 10-tetrahydrobenzo [a] pyrene (BPDE), forms predominantly N-2-deoxyguanine DNA adducts in two stereoisomeric configurations (cis and trans). In previous in vitro assays using oligonucleotide substrates site specifically modified with cis- and trans-BPDE adducts, the nucleotide excision repair (NER) systems of eukaryotes and prokaryotes incise cis-BPDE adducts more efficiently than trans-BPDE adducts [Hess, et al. (1997) Mol. Cell Blol 17, 7069; Zou, et al. (2001) Biochemistry 40, 2923). We investigated the influence of DNA secondary structure on stereospecificity of BPDE adduct formation, and incision of BPDE adducts by the prokaryotic UvrABC NER endonuclease was examined. BPDE adducts formed at low density on supercoiled plasmids were incised 6-7-fold better by the thermoresistant Bacillus caldotenax UvrABC than were BPDE adducts formed on linear DNA. Linearizing supercoiled plasmid DNAs after BPDE adduct formation did not diminish incision efficiency. These results suggested that configuration and/or conformation of adducts formed on linear and supercoiled DNAs differed. This hypothesis was confirmed by low temperature fluorescence spectroscopy of adducted supercoiled and linear DNAs. Spectroscopic results indicated that intercalated cis-BPDE adducts as well as base-stacked trans-BPDE adducts formed more abundantly in supercoiled DNA than in linear DNA. A higher cis to trans adduct ratio in supercoiled DNA was confirmed by high resolution [P-32]postlabeling analyses. These results demonstrate that DNA secondary structure influences both configuration and conformation of BPDE adducts formed at low density (similar to1 adduct/kbp) and suggests that the ratio of cis- to trans-BPDE adducts and amount of base-stacked trans adducts formed under physiological exposure conditions may be higher than inferred from high dose experiments. C1 Univ Louisville, Dept Pharmacol & Toxicol, Louisville, KY 40292 USA. US DOE, Ames Lab, Ames, IA 50011 USA. Iowa State Univ, Dept Chem, Ames, IA 50011 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP States, JC (reprint author), Univ Louisville, Dept Pharmacol & Toxicol, Louisville, KY 40292 USA. EM jcstates@louisville.edu RI States, J./H-4246-2011 FU NIEHS NIH HHS [1R01-ES06460] NR 38 TC 12 Z9 13 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD MAR PY 2004 VL 17 IS 3 BP 330 EP 339 DI 10.1021/tx034184h PG 10 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 804MU UT WOS:000220303600007 PM 15025503 ER PT J AU Mijal, RS Thomson, NM Fleischer, NL Pauly, GT Moschel, RC Kanugula, S Fang, QM Pegg, AE Peterson, LA AF Mijal, RS Thomson, NM Fleischer, NL Pauly, GT Moschel, RC Kanugula, S Fang, QM Pegg, AE Peterson, LA TI The repair of the tobacco specific nitrosamine derived adduct O-6-[4-oxo-4-(3-pyridyl)butyl]guanine by O-6-alkylguanine-DNA alkyltransferase variants SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID HUMAN O6-ALKYLGUANINE-DNA ALKYLTRANSFERASE; ESCHERICHIA-COLI ADA; A/J MICE; O-6-METHYLGUANINE-DNA METHYLTRANSFERASE; O(6)-ALKYLGUANINE-DNA ALKYLTRANSFERASE; CHEMICAL CARCINOGENESIS; LUNG-TUMORS; DEUTERIUM SUBSTITUTION; DNA ADDUCTS; MOUSE LUNG AB The tobacco specific nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), a potent pulmonary carcinogen, both methylates and pyridyloxobutylates DNA. Both reaction pathways generate promutagenic O-6-alkylguanine adducts. These adducts, O-6-methylguanine (O-6-mG) and O-6- [4-oxo-4-(3-pyridyl)butyl] guanine (O-6-pobG), are repaired by O-6-alkylguanineDNA alkyltransferase (AGT). In this report, we demonstrate that pyridyloxobutyl DNA adducts are repaired by AGT in a reaction that results in pyridyloxobutyl transfer to the active site cysteine. Because minor changes within the binding pocket of AGT can alter the ability of this protein to repair bulky O-6-alkylguanine adducts relative to O-6-mG, we explored the ability of AGTs from different species as well as several human AGT variants and mutants to discriminate between O-6-mG or O-6-pobG adducts. We incubated proteins with equal molar amounts of oligodeoxynucleotides containing site specifically incorporated O-6-mG or O-6-pobG and measured repair. Bacterial AGTs poorly repaired O-6-pobG. Mouse and rat AGT repaired both adducts at comparable rates. Wild-type human AGT, variant I143V/K178R, and mutant N157H repaired O-6-mG approximately twice as fast as O-6-pobG. Human variant G160R and mutants P140K, Y158H, G156A, and E166G did not repair O-6-pobG until all of the O-6-mG was removed. To understand the role of adduct structure on relative repair rates, the competition experiments were repeated with two other bulky O-6-alkylguanine adducts, O-6-butylguanine (O-6-buG) and O-6-benzylguanine (O-6-bzG). The proteins displayed similar repair preference of O-6-mG relative to O-6-buG as observed with O-6-pobG. In contrast, all of the mammalian proteins, except the mutant P140K, preferentially repaired O-6-bzG. These studies indicate that the rate of repair of O-6-pobG is highly dependent on protein structure. Inefficient repair of O-6-pobG by bacterial AGT explains the high mutagenic activity of this adduct in bacterial systems. In addition, differences observed in the repair of this adduct by mammalian proteins may translate into differences in sensitivity to the mutagenic and carcinogenic effects of NNK or other pyridyloxobutylating nitrosamines. C1 Univ Minnesota, Div Environm & Occupat Hlth, Minneapolis, MN 55455 USA. Univ Minnesota, Ctr Canc, Minneapolis, MN 55455 USA. NCI, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. Penn State Univ, Milton S Hershey Med Ctr, Coll Med, Dept Cellular & Mol Physiol, Hershey, PA 17033 USA. RP Peterson, LA (reprint author), Univ Minnesota, Div Environm & Occupat Hlth, Minneapolis, MN 55455 USA. EM peter431@umn.edu RI Fang, Qingming/B-6839-2008; OI Fang, Qingming/0000-0002-4006-0636; Peterson, Lisa/0000-0001-8715-4480 FU NCI NIH HHS [CA-18137, CA-59887]; NIEHS NIH HHS [ES-10956] NR 64 TC 46 Z9 48 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD MAR PY 2004 VL 17 IS 3 BP 424 EP 434 DI 10.1021/tx0342417 PG 11 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 804MU UT WOS:000220303600018 PM 15025514 ER PT J AU Hang, HC Yu, C Ten Hagen, KG Tian, E Winans, KA Tabak, LA Bertozzi, CR AF Hang, HC Yu, C Ten Hagen, KG Tian, E Winans, KA Tabak, LA Bertozzi, CR TI Small molecule inhibitors of mucin-type O-linked glycosylation from a uridine-based library SO CHEMISTRY & BIOLOGY LA English DT Article ID POLYPEPTIDE N-ACETYLGALACTOSAMINYLTRANSFERASE; ACETYL-D-GALACTOSAMINE; ALPHA-D-GALACTOSAMINE; BOVINE UDP-GALNAC; SIALYL-LEWIS-X; CDNA CLONING; OLIGOSACCHARYL TRANSFERASE; DROSOPHILA-MELANOGASTER; ACCEPTOR SPECIFICITY; EXPRESSION PATTERNS AB The polypeptide N-acetyl-alpha-galactosaminyltransferases (ppGalNAcTs, also abbreviated ppGaNTases) initiate mucin-type O-linked glycosylation and therefore play pivotal roles in cell-cell communication and protection of tissues. In order to develop new tools for studying mucin-type O-linked glycosylation, we screened a 1338 member uridine-based library to identify small molecule inhibitors of ppGalNAcTs. Using a high-throughput enzyme-linked lectin assay (ELLA), two inhibitors of murine ppGalNAcT-1 (K-I similar to 8 muM) were identified that also inhibit several other members of the family. The compounds did not inhibit other mammalian glycosyltransferases or nucleotide sugar utilizing enzymes, suggesting selectivity for the ppGalNAcTs. Treatment of cells with the compounds abrogated mucin-type O-linked glycosylation but not N-linked glycosylation and also induced apoptosis. These uridine analogs represent the first generation of chemical tools to study the functions of mucin-type O-linked glycosylation. C1 Univ Calif Berkeley, Ctr New Direct Organ Synth, Dept Chem, Berkeley, CA 94720 USA. Univ Calif Berkeley, Ctr New Direct Organ Synth, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. Univ Calif Berkeley, Ctr New Direct Organ Synth, Howard Hughes Med Inst, Berkeley, CA 94720 USA. NIDDK, Sect Biol Chem, NIH, Bethesda, MD USA. RP Bertozzi, CR (reprint author), Univ Calif Berkeley, Ctr New Direct Organ Synth, Dept Chem, Berkeley, CA 94720 USA. EM crb@berkeley.edu FU NIGMS NIH HHS [GM66047] NR 65 TC 36 Z9 36 U1 1 U2 9 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-5521 J9 CHEM BIOL JI Chem. Biol. PD MAR PY 2004 VL 11 IS 3 BP 337 EP 345 DI 10.1016/j.chembiol.2004.02.023 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 807LL UT WOS:000220502900010 PM 15123263 ER PT J AU Wallace, D Hildesheim, A Pinto, LA AF Wallace, D Hildesheim, A Pinto, LA TI Comparison of benchtop microplate beta counters with the traditional gamma counting method for measurement of chromium-51 release in cytotoxic assays SO CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY LA English DT Article ID CELL-MEDIATED CYTOTOXICITY; PERIPHERAL-BLOOD; CR-51 RELEASE; VITRO; RESPONSES; VIRUSES AB The most traditional method used to measure the lytic activity of cytotoxic T lymphocytes or natural killer (NK) cells is the chromium release assay (CRA). No study has been reported that systematically compares the traditional gamma counting method with various benchtop microplate scintillation formats to measure chromium release. Here we investigated the utilization of microplate beta counters in comparison with the traditional gamma counting method to quantitate antigen-specific cytolysis, lymphokine-activated killer (LAK) activity, and NK activity in the CRA. Supernatants from standard CRA (n = 7) were directly transferred to a 96-well microplate containing either a solid scintillant (Lumaplate) or a liquid scintillant (flexible beta plate). Samples were quantified by using two benchtop microplate beta counters, Wallac Microbeta Trilux (Lumalux and Trilux methods, respectively) and Packard TopCount instruments (TopCount method). These results were then compared with data from an identical assay run in parallel using the traditional gamma counting method (LKB). The lytic activity for influenza virus-stimulated effectors measured in the benchtop microplate beta counters using Lumalux and Trilux methods exhibited excellent correlations with the one measured in the traditional LKB (r = 0.967 and 0.968, respectively). The TopCount method demonstrated a similar correlation (r = 0.966). Similar findings were observed for LAK and NK activity. The 96-well microplate format, specifically the dry-scintillant Lumaplates, offers several advantages over the traditional gamma counting format. Most notable are the reductions in sample volume needed and in the total sample preparation and counting time. Furthermore, this system reduces the amount of dry and mixed radioactive waste generated while using the same instrument for gamma- and beta-emitting isotopes. C1 NCI, SAIC, HPV Immunol Lab, Ft Detrick, MD 21702 USA. NIH, Div Canc Epidemiol & Genet, Bethesda, MD USA. RP Pinto, LA (reprint author), NCI, SAIC, HPV Immunol Lab, POB B,Bldg 469, Ft Detrick, MD 21702 USA. EM lpinto@ncifcrf.gov FU NCI NIH HHS [N01-CO-12400, N01CO12400] NR 13 TC 9 Z9 11 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1071-412X J9 CLIN DIAGN LAB IMMUN JI Clin. Diagn. Lab. Immunol. PD MAR PY 2004 VL 11 IS 2 BP 255 EP 260 DI 10.1128/CDLI.11.2.255-260.2004 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 807DV UT WOS:000220483100005 PM 15013972 ER PT J AU Castle, PE Rodriguez, AC Bowman, FP Herrero, R Schiffman, M Bratti, MC Morera, LA Schust, D Crowley-Nowick, P Hildesheim, A AF Castle, PE Rodriguez, AC Bowman, FP Herrero, R Schiffman, M Bratti, MC Morera, LA Schust, D Crowley-Nowick, P Hildesheim, A TI Comparison of ophthalmic sponges for measurements of immune markers from cervical secretions SO CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY LA English DT Article ID HUMAN-PAPILLOMAVIRUS; COLLECTION; CYTOKINES; VIRUS; WOMEN AB Measurements of cervical immunity are important for evaluating immune responses to infections of the cervix and to vaccines for preventing those infections. Three ophthalmic sponges, Weck-Cel, Ultracell, and Merocel, were loaded in vitro with interieukin-1beta (IL-10), IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-15, IL-18, gamma interferon (IFN-gamma), granulocyte-macrophage colony-stimulating factor (GM-CSF), immunoglobulin A (IgA), or IgG, and sponges were extracted and evaluated for total recovery by enzyme-linked immunosorbent assay (ELISA). There was excellent (>75%) recovery for all immune markers from all three devices except for IL-6, which was poorly recovered (<60%) for all sponge types, IFN-gamma, which was poorly recovered from both Weck-Cel and Ultracell sponges but was completely recovered from Merocel sponges, and IL-4, which was poorly recovered from Weck-Cel sponges but was completely recovered from Ultracell or Merocel sponges. We then compared the absolute recovery of selected markers (IL-10, IL-12, IgG, and IgA) from cervical secretion specimens collected from women using each type of sponge. There were no significant differences in the recoveries of IL-10, IL-12, and IgG from cervical specimens collected by any type of ophthalmic sponge, but there was reduced IgA recovery from Merocel sponges. However, the variability in these measurements attributable to sponge types (1 to 3%) was much less than was attributable to individuals (45 to 72%), suggesting that differences in sponge type contribute only in a minor way to these measurements. We infer from our data that the three collection devices are adequate for the measurements of IL-10, IL-2, IL-5, IL-12, IL-15, IL-18, and IgG. Merocel may be a better ophthalmic sponge for the collection of cervical secretions and measurements of IL-4, IL-8, IL-10, GM-CSF, and IFN-gamma, but our data from clinical specimens, not in vitro-loaded sponges, suggested the possibility of reduced recovery of IgA. These findings require confirmation. C1 NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. Proyecto Epidemiol Guanacaste, San Jose, Costa Rica. Harvard Univ, Sch Med, Brigham & Womens Hosp, Fearing Res Lab,Dept Obstet, Boston, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Fearing Res Lab,Dept Gynecol, Boston, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Fearing Res Lab,Dept Reprod Biol, Boston, MA USA. RP Castle, PE (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, DHHS, 6120 Execut Blvd,MSC 7234, Bethesda, MD 20892 USA. EM castlep@mail.nih.gov NR 19 TC 20 Z9 20 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1071-412X J9 CLIN DIAGN LAB IMMUN JI Clin. Diagn. Lab. Immunol. PD MAR PY 2004 VL 11 IS 2 BP 399 EP 405 DI 10.1128/CDLI.11.2.399-405.2004 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 807DV UT WOS:000220483100027 PM 15013994 ER PT J AU Mulshine, JL Atkinson, JC Greer, RO Papadimitrakopoulou, VA Van Waes, C Rudy, S Martin, JW Steinberg, SM Liewehr, DJ Avis, I Linnoila, RI Hewitt, S Lippman, SM Frye, R Cavanaugh, PF AF Mulshine, JL Atkinson, JC Greer, RO Papadimitrakopoulou, VA Van Waes, C Rudy, S Martin, JW Steinberg, SM Liewehr, DJ Avis, I Linnoila, RI Hewitt, S Lippman, SM Frye, R Cavanaugh, PF TI Randomized, double-blind, placebo-controlled phase IIB trial of the cyclooxygenase inhibitor ketorolac as an oral rinse in oropharyngeal leukoplakia SO CLINICAL CANCER RESEARCH LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; GASTROINTESTINAL CLINICAL EVENTS; GINGIVAL CREVICULAR FLUID; UPPER AERODIGESTIVE TRACT; ACTINIC KERATOSES; PERIODONTAL-DISEASE; HELICOBACTER-PYLORI; ASPIRIN USE; BONE LOSS; CANCER AB Purpose: Nonselective cyclooxygenase (COX) inhibitors have been reported to decrease the frequency of upper aerodigestive cancers. Ketorolac tromethamine oral rinse has been shown to resolve another COX-dependent process, periodontal disease, without incurring gastrointestinal side effects. This trial evaluated if a topically delivered oral rinse containing ketorolac was as safe as and more effective than oral rinse alone in reducing the area of oral leukoplakia. Experimental Design: 57 patients were randomized (2:1 ratio) in a double-blind, placebo-controlled study of ketorolac (10 ml of a 0.1% ketorolac rinse solution; n = 38) or placebo (10 ml of rinse solution; n = 19) given twice daily for 30 s over 90 days. Primary end point was evaluated visually obtaining bidimensional measurement of the size of leukoplakia lesion(s) at entry and at 90 days. Secondary end point was histological assessment of the leukoplakia as sampled by serial punch biopsy and independently reviewed by three pathologists. Results: The patients included 67% males, 11% nonCaucasian, and 86% used tobacco with no significant differences between the two arms. Both rinses were well tolerated with good compliance, and there was no significant difference in adverse events (P = 0.27). Major response rate (complete response and partial response) was 30% for ketorolac and 32% for the placebo arm. There was no significant difference in change in histology between the two arms. Conclusion: Local delivery of a COX-containing oral rinse was well tolerated but produced no significant reduction in the extent of leukoplakia compared with the placebo. However, the favorable response rate to placebo arm remains unexplained and additional investigation of the tissue penetration with ketorolac is warranted. C1 NCI, Cell & Canc Biol Branch, Upper Aerodigest Chemoprevent Fac, Canc Res Ctr,Intervent Sect,NIH, Bethesda, MD 20892 USA. Procter & Gamble Co, Over Counter Hlth Care Technol Div, Mason, OH USA. Natl Inst Deafness & Other Commun Disorders, Head & Neck Surg Branch, Bethesda, MD USA. Univ Texas, MD Anderson Canc Ctr, Dept Clin Canc Prevent, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Head & Neck Surg, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Thorac Head & Neck Med Oncol, Houston, TX 77030 USA. Univ Colorado, Ctr Canc, Denver, CO 80262 USA. Univ Colorado, Sch Dent, Div Oral Pathol & Oncol, Denver, CO 80262 USA. Natl Inst Dent & Craniofacial Res, Clin Res core, Bethesda, MD USA. NCI, Dept Pathol, NIH, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, NIH, Bethesda, MD 20892 USA. RP Mulshine, JL (reprint author), NCI, Cell & Canc Biol Branch, Upper Aerodigest Chemoprevent Fac, Canc Res Ctr,Intervent Sect,NIH, Bldg 10,room 12N226, Bethesda, MD 20892 USA. EM mulshinj@mail.nih.gov OI Hewitt, Stephen/0000-0001-8283-1788 FU NCI NIH HHS [P50-CA58187, P50-CA70907-06] NR 63 TC 43 Z9 46 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAR 1 PY 2004 VL 10 IS 5 BP 1565 EP 1573 DI 10.1158/1078-0432.CCR-1020-3 PG 9 WC Oncology SC Oncology GA 801IH UT WOS:000220089100004 PM 15014005 ER PT J AU Ueki, T Hsing, AW Gao, YT Wang, BS Shen, MC Cheng, JR Deng, J Fraumeni, JF Rashid, A AF Ueki, T Hsing, AW Gao, YT Wang, BS Shen, MC Cheng, JR Deng, J Fraumeni, JF Rashid, A TI Alterations of p16 and prognosis in biliary tract cancers from a population-based study in China SO CLINICAL CANCER RESEARCH LA English DT Article ID TUMOR-SUPPRESSOR GENE; CELL-CYCLE CONTROL; HEPATOCELLULAR-CARCINOMA; PANCREATIC ADENOCARCINOMA; MOLECULAR EPIDEMIOLOGY; HOMOZYGOUS DELETIONS; SOMATIC MUTATIONS; NITRIC-OXIDE; METHYLATION; INACTIVATION AB Purpose: Biliary tract cancer is an uncommon malignancy with a poor survival rate. We evaluated p16 gene alteration as a prognostic marker for this disease. Experimental Design: We studied p16 gene alterations by sequencing, methylation, and loss of heterozygosity of chromosome 9p in 118 biliary tract carcinomas, including 68 gallbladder cancers, 33 extrahepatic bile duct cancers, and 17 ampullary cancers. Survival was evaluated in 57 patients with gallbladder carcinomas, 27 with bile duct carcinomas, and 16 with ampullary carcinomas with and without somatic p16 alterations detected by two different methods. Results: p16 gene alterations including silent mutations were present in 61.8% gallbladder cancers, 54.5% bile duct cancers, and 70.6% ampullary cancers. p16 gene nonsilent mutations, p16 methylation, and loss of chromosome 9p21-22 that targets p14, p15, and p16 genes were present in 13 of 53 (24.5%), 8 of 54 (14.8%), and 32 of 44 (72.7%) gallbladder tumors; 5 of 25 (20.0%), 5 of 31 (16.1%), and 12 of 21 (57.1%) bile duct tumors; and 3 of 13 (23.1%), 6 of 15 (40.0%), and 8 of 16 (50.0%) ampullary tumors, respectively. The mean survival of patients with gallbladder cancers without p16 alterations was 21.5 +/- 14.8 months compared with 12.1 +/- 11.4 months for patients with p16 alterations (P = 0.02). Conclusions: Alteration of p16 gene alone or in combination with alterations of other tumor suppressor genes on chromosome 9p is a prognostic indicator in gallbladder carcinoma, with more favorable survival rates associated with carcinomas lacking p16 gene alterations. C1 Univ Texas, MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Ctr Oncol, Baltimore, MD 21205 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Shanghai Canc Inst, Shanghai, Peoples R China. Zhongshan Hosp, Dept Gen Surg, Shanghai, Peoples R China. Shanghai Canc Hosp, Dept Pathol, Shanghai, Peoples R China. RP Rashid, A (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Pathol, Box 85,1515 Holcombe Blvd, Houston, TX 77030 USA. EM arashid@mdanderson.org NR 52 TC 33 Z9 35 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAR 1 PY 2004 VL 10 IS 5 BP 1717 EP 1725 DI 10.1158/1078-0432.CCR-1137-3 PG 9 WC Oncology SC Oncology GA 801IH UT WOS:000220089100023 PM 15014024 ER PT J AU Vitolo, JM Cotrim, AP Sowers, AL Russo, A Wellner, RB Pillemer, SR Mitchell, JB Baum, BJ AF Vitolo, JM Cotrim, AP Sowers, AL Russo, A Wellner, RB Pillemer, SR Mitchell, JB Baum, BJ TI The stable nitroxide tempol facilitates salivary gland protection during head and neck irradiation in a mouse model SO CLINICAL CANCER RESEARCH LA English DT Article ID RAT SUBMANDIBULAR-GLANDS; SUPEROXIDE-DISMUTASE; X-IRRADIATION; PAROTID-GLAND; RADIATION; RADIOPROTECTION; WR-2721; CANCER; DAMAGE; SECRETION AB Purpose: Radiotherapy is commonly used to treat a majority of patients with head and neck cancers. The long-term radiation-induced reduction of saliva output significantly contributes to the posttreatment morbidity experienced by these patients. The purpose of this study was to test the ability of the stable-free radical Tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl), an established radioprotector, to prevent radiation-induced salivary hypofunction in mice. Experimental Design: The heads of C3H mice were exposed to a range of single radiation doses with or without an i.p. injection of 275 mg/kg Tempol 10 min before treatment. Salivary gland output was assessed 8 weeks postirradiation. Results: Radiation caused a dose-dependent reduction in salivary flow in this model. Tempol treatment alone significantly reduced radiation-induced salivary hypofunction. The combination of Tempol with mouth/nose shielding showed essentially complete radiation protection at 15 Gy and similar to75% protection at 17.5 Gy. Conclusions: This study demonstrates for the first time that significant radioprotection of the salivary glands is possible with Tempol in C3H mice. C1 Natl Inst Dent & Craniofacial Res, Gene Therapy & Therapeut Branch, NIH, Bethesda, MD 20892 USA. NCI, Radiat Biol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Baum, BJ (reprint author), Natl Inst Dent & Craniofacial Res, Gene Therapy & Therapeut Branch, NIH, Bldg 10,Room 1N113,MSC-1190, Bethesda, MD 20892 USA. EM bbaum@dir.nidcr.nih.gov NR 47 TC 52 Z9 55 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAR 1 PY 2004 VL 10 IS 5 BP 1807 EP 1812 DI 10.1158/1078-0432.CCR-03-0194 PG 6 WC Oncology SC Oncology GA 801IH UT WOS:000220089100034 PM 15014035 ER PT J AU Nguyen, DM Schrump, WD Chen, GA Tsai, W Nguyen, P Trepel, JB Schrump, DS AF Nguyen, DM Schrump, WD Chen, GA Tsai, W Nguyen, P Trepel, JB Schrump, DS TI Abrogation of p21 expression by flavopiridol enhances depsipeptide-mediated apoptosis in malignant pleural mesothelioma cells SO CLINICAL CANCER RESEARCH LA English DT Article ID HISTONE DEACETYLASE INHIBITOR; DEPENDENT KINASE INHIBITOR; 3/P21 COMPLEX-FORMATION; HUMAN LEUKEMIA-CELLS; LUNG-CANCER CELLS; PROTOONCOGENE EXPRESSION; DIFFERENTIAL MODULATION; MOLECULAR INTERVENTION; GROWTH ARREST; P53 STABILITY AB Purpose: Recent insights regarding the pathogenesis of malignant pleural mesothelioma (MPM) provide new opportunities for targeted molecular therapies for this highly lethal disease. The present study was undertaken to examine the effects of the histone deacetylase inhibitor, Depsipeptide (DP) FK228, in conjunction with the cyclin-dependent kinase inhibitor, Flavopiridol (FLA), in cultured MPM cells. Experimental Design: Proliferation and apoptosis in drug-treated, virally transduced, or control cells were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and Apo-bromodeoxyuridine techniques. Western blot and ELISA techniques were used to examine signal transduction and cell cycle-related protein levels in MPM cells exposed to DP and/or FLA in the presence or absence of calphostin, phorbol-12,13-dibutyrate, 5,6-dichloro-1-beta-D-ribofuranosyl-benzimidazole, or adenoviral p21 transduction. Results: DP (1-50 ng/ml x 6 h) or FLA (100-200 nM x 72 h) alone, mediated low-level, dose-dependent growth inhibition in MPM cells. In contrast, sequential DP/FLA treatment mediated marked growth inhibition and apoptosis in these cell lines. The cytotoxic effects of DP/FLA were considerably less pronounced in cultured normal cells. The proapoptotic effects of DP/FLA treatment coincided with inhibition of DP-mediated induction of p21 by FLA. Overexpression of p21 by adenoviral gene transfer techniques rendered MPM cells refractory to the cytotoxic effects of this treatment regimen. In p21 reporter assays, promoter activation by DP was antagonized by FLA. The magnitude of inhibition of DP-mediated p21 induction by FLA exceeded that observed with the pTEFb antagonist 5,6-dichloro-1-beta-D-ribofuranosyl-benzimidazole. Calphostin C abrogated p21 induction mediated by DP and enhanced DP-mediated apoptosis in a manner comparable with FLA in MPM cells; in contrast, phorbol-12,13-dibutyrate blocked FLA-mediated inhibition of p21 induction by DP and markedly protected these cells from the apoptotic effects of sequential DP/FLA. Conclusions: FLA abrogates DP-mediated induction of p21 expression, in part, via inhibition of protein kinase C signaling and markedly potentiates the cytotoxic effects of DP in MPM cells. C1 NCI, Thorac Oncol Sect, Surg Branch, NIH, Bethesda, MD 20892 USA. NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. NCI, Med Oncol Clin Res Unit, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Schrump, DS (reprint author), NCI, Thorac Oncol Sect, Surg Branch, NIH, Bldg 10,Room 2B-07,10 Ctr Dr, Bethesda, MD 20892 USA. EM David_Schrump@nih.gov NR 53 TC 70 Z9 72 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAR 1 PY 2004 VL 10 IS 5 BP 1813 EP 1825 DI 10.1158/1078-0432.CCR-0901-3 PG 13 WC Oncology SC Oncology GA 801IH UT WOS:000220089100035 PM 15014036 ER PT J AU Fowler, DH Foley, J Hou, JWS Odom, J Castro, K Steinberg, SM Gea-Banacloche, J Kasten-Sportes, C Gress, RE Bishop, MR AF Fowler, Daniel H. Foley, Jason Hou, Jeannie Whit-Shan Odom, Jeanne Castro, Kate Steinberg, Seth M. Gea-Banacloche, Juan Kasten-Sportes, Claude Gress, Ronald E. Bishop, Michael R. TI Clinical "Cytokine Storm" as Revealed by Monocyte Intracellular Flow Cytometry: Correlation of Tumor Necrosis Factor alpha With Severe Gut Graft-Versus-Host Disease SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article AB Background & Aims: Gut graft-versus-host disease (GVHD) contributes significantly to lethality after allogeneic hematopoietic stem-cell transplantation (HSCT). In murine models, macrophage secretion of interleukin 1 alpha (IL-1 alpha) and tumor necrosis factor alpha (TNF-alpha) contributes to gut GVHD pathogenesis. To help characterize whether human gut GVHD has similar biological characteristics, monocyte IL-1 alpha and TNF-alpha production were evaluated after HSCT. Methods: Patients withrefractory hematologic malignancy (n = 17) underwent reduced-intensity conditioning, HLA-matched sibling HSCT, and cyclosporine A GVHD prophylaxis. After HSCT, monocyte IL-1 alpha and TNF-alpha levels were measured using intracellular flow cytometry (IC-FCM), and results were correlated with clinical GVHD. Results: Incidences of acute GVHD were none (n = 3), grades I-II (n = 9), or grades III-IV (n = 5; each case with stage 2-3 gut GVHD). Posttransplantation monocyte IL-1 alpha production (percentage of CD14(+) IL-1(+) cells) increased significantly from 8.7% +/- 3.7% (week 2) to 40.3% +/- 7.3% (week 4; P = 0.0065) and was not associated with GVHD severity (P = 1.00). Conversely, increases in monocyte TNF-alpha were quantitatively reduced and temporally delayed, from 0.6% +/- 0.2% (week 2) to 3.6% +/- 1.4% (week 6; P = 0.076). Most importantly, elevation of monocyte TNF-alpha level correlated with increased gut GVHD severity (P = 0.0041); increases in monocyte TNF-alpha levels typically preceded the onset of gut GVHD symptoms. Conclusions: Human gut GVHD after reduced-intensity allogeneic HSCT is associated with monocyte cytokine secretion initially involving IL-1 alpha, followed by TNF-alpha. Serial measurement of monocyte cytokines, in particular, TNF-alpha, by IC-FCM may represent a noninvasive method for GVHD monitoring, potentially allowing the identification of patients appropriate for early-intervention strategies. C1 [Fowler, Daniel H.; Foley, Jason; Hou, Jeannie Whit-Shan; Odom, Jeanne; Castro, Kate; Gea-Banacloche, Juan; Kasten-Sportes, Claude; Gress, Ronald E.; Bishop, Michael R.] NCI, Dept Expt Transplantat & Immunol, Ctr Canc Res, Bethesda, MD 20892 USA. [Steinberg, Seth M.] NCI, Biostat & Data Management Sect, Ctr Canc Res, Bethesda, MD 20892 USA. RP Fowler, DH (reprint author), NIH, 9000 Rockville Pike,Bldg 10,Room 12N226, Bethesda, MD 20892 USA. EM hfowler@helix.nih.gov NR 47 TC 32 Z9 36 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD MAR PY 2004 VL 2 IS 3 BP 237 EP 245 DI 10.1053/S1542-3565(04)00011-4 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA V19KO UT WOS:000208071500008 PM 15017608 ER PT J AU Wu, YR Lin, HY Chen, CM Gwinn-Hardy, K Ro, LS Wang, YC Li, SH Hwang, JC Fang, K Hsieh-Li, HM Li, ML Tung, LC Su, MT Lee-Chen, G Lee-Chen, G AF Wu, YR Lin, HY Chen, CM Gwinn-Hardy, K Ro, LS Wang, YC Li, SH Hwang, JC Fang, K Hsieh-Li, HM Li, ML Tung, LC Su, MT Lee-Chen, G Lee-Chen, G TI Genetic testing in spinocerebellar ataxia in Taiwan: expansions of trinucleotide repeats in SCA8 and SCA17 are associated with typical Parkinson's disease SO CLINICAL GENETICS LA English DT Article DE genetic testing; phenotypical variability; SCA8 and SCA17; trinucleotide-repeat expansion ID TATA-BINDING PROTEIN; MACHADO-JOSEPH-DISEASE; CAG-REPEAT; CEREBELLAR-ATAXIA; CLINICAL ANALYSIS; CTG EXPANSION; ALLELES; LOCUS; POLYGLUTAMINE; FAMILIES AB DNA tests in normal subjects and patients with ataxia and Parkinson's disease (PD) were carried out to assess the frequency of spinocerebellar ataxia (SCA) and to document the distribution of SCA mutations underlying ethnic Chinese in Taiwan. MJD/SCA3 (46%) was the most common autosomal dominant SCA in the Taiwanese cohort, followed by SCA6 (18%) and SCA1 (3%). No expansions of SCA types 2, 10, 12, or dentatorubropallidoluysian atrophy (DR-PLA) were detected. The clinical phenotypes of these affected SCA patients were very heterogeneous. All of them showed clinical symptoms of cerebellar ataxia, with or without other associated features. The frequencies of large normal alleles are closely associated with the prevalence of SCA1, SCA2, MJD/SCA3, SCA6, and DRPLA among Taiwanese, Japanese, and Caucasians. Interestingly, abnormal expansions of SCA8 and SCA 17 genes were detected in patients with PD. The clinical presentation for these patients is typical of idiopathic PD with the following characteristics: late onset of disease, resting tremor in the limbs, rigidity, bradykinesia, and a good response to levodopa. This study appears to be the first report describing the PD phenotype in association with an expanded allele in the TATA-binding protein gene and suggests that SCA8 may also be a cause of typical PD. C1 Natl Taiwan Normal Univ, Dept Life Sci, Taipei 117, Taiwan. Chang Gung Mem Hosp, Dept Neurol 2, Taipei 10591, Taiwan. NINDS, Neurogenet Branch, Parkinsons Unit, Bethesda, MD 20892 USA. RP Lee-Chen, G (reprint author), Natl Taiwan Normal Univ, Dept Life Sci, Taipei 117, Taiwan. EM cmchen@adm.cgmh.org.tw; +43019@cc.ntnul.edu.tn RI Gwinn, Katrina/C-2508-2009 NR 47 TC 52 Z9 53 U1 1 U2 5 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0009-9163 J9 CLIN GENET JI Clin. Genet. PD MAR PY 2004 VL 65 IS 3 BP 209 EP 214 DI 10.1111/j.0009-9163.2004.00213.x PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 780JA UT WOS:000189376300008 PM 14756671 ER PT J AU Roederer, M Brenchley, JM Betts, MR De Rosa, SC AF Roederer, M Brenchley, JM Betts, MR De Rosa, SC TI Flow cytometric analysis of vaccine responses: how many colors are enough? SO CLINICAL IMMUNOLOGY LA English DT Article DE flow cytometry; vaccines; fluorescence parameters ID CD8(+) T-CELLS; DISTRIBUTION DIFFERENCES/; SUBSETS; MEMORY; NAIVE; IDENTIFICATION; LYMPHOCYTES; PHENOTYPE; HIV-1 AB The past 5 years have seen an explosion in technological advances related to measuring immunogenicity. Specifically, two distinct areas of development have led to considerably more detailed analysis of T cell responses: first, the ability to measure over a dozen distinct antigens expressed by individual cells simultaneously (12-color flow cytometry); and second, a host of assays that rapidly and viably identify antigen-specific T cells. Together, these technologies reveal the complex heterogeneity of an immune response generated during infection or after vaccine challenge. The next 5 years will see the determination of which underlying variables will be most important to quantifying vaccine efficacy. In this manuscript, we discuss these technologies, with a focus on assisting in the design and implementation of inummogenicity trials for future vaccine efforts. (C) 2003 Elsevier Inc. All rights reserved. C1 NIAID, Immunotechnol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Roederer, M (reprint author), NIAID, Immunotechnol Sect, Vaccine Res Ctr, NIH, 40 Convent Dr,Room 5509, Bethesda, MD 20892 USA. EM Roederer@nih.gov RI Roederer, Mario/G-1887-2011 NR 19 TC 44 Z9 48 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD MAR PY 2004 VL 110 IS 3 BP 199 EP 205 DI 10.1016/j.clim.2003.11.015 PG 7 WC Immunology SC Immunology GA 812HY UT WOS:000220831800002 PM 15047198 ER PT J AU Beisel, CE Morens, DM AF Beisel, CE Morens, DM TI Variant Creutzfeldt-Jakob disease and the acquired and transmissible spongiform encephalopathies SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID RESISTANT PRION PROTEIN; CONGO RED; SCRAPIE; BSE; INHIBITION; AGENT; PROPAGATION; HUMANS; SHEEP; KURU AB In 1995 a fatal epidemic of spongiform encephalopathy appeared in Great Britain. The new epidemic condition was clinically and pathologically similar to Creutzfeldt-Jakob disease (CJD), a rare sporadic encephalopathy, and was called "variant CJD" (vCJD). The vCJD epidemic was detected by active epidemiologic surveillance, which had been set up in response to a British epizootic of another new disease called "bovine spongiform encephalopathy" (BSE). Widespread cattle exposure to the BSE agent (a prion) had presumably been occurring in Britain since about 1982, when changes in the rendering process allowed infected material to contaminate cattle feed. Concern that the bovine disease might transmit to humans via beef consumption led to the active surveillance program. Tragically, BSE transmission to humans appears to have led to over 100 cases of vCJD. Millions of affected cattle were eventually slaughtered throughout Europe. Cattle are now routinely tested for BSE at 24-30 months of age, and affected herds are destroyed. These measures have exponentially reduced the BSE epizootic. Britain and other European countries that received contaminated beef or cattle feed nevertheless remain concerned about the combination of nearly universal past human exposure in Britain, variable exposure elsewhere, an unknown incubation period, vCJD case totals that continue to mount, and worst-case predictions that extend to many thousands of eventual human cases. C1 NIAID, NIH, Bethesda, MD 20892 USA. RP Morens, DM (reprint author), NIAID, NIH, 6610 Rockledge Dr, Bethesda, MD 20892 USA. EM dmorens@niaid.nih.gov NR 41 TC 18 Z9 22 U1 0 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD MAR 1 PY 2004 VL 38 IS 5 BP 697 EP 704 DI 10.1086/381028 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 777EY UT WOS:000189163900014 PM 14986255 ER PT J AU Dean, RM Bishop, MR AF Dean, RM Bishop, MR TI Allogeneic hematopoietic stem cell transplantation for lymphoma SO CLINICAL LYMPHOMA LA English DT Review ID BONE-MARROW-TRANSPLANTATION; NON-HODGKINS-LYMPHOMA; CHRONIC LYMPHOCYTIC-LEUKEMIA; LOW-GRADE LYMPHOMA; HIGH-DOSE THERAPY; MINIMAL RESIDUAL DISEASE; 1ST COMPLETE REMISSION; TREATMENT-RELATED MORTALITY; DONOR LEUKOCYTE INFUSIONS; GRAFT-VERSUS-MALIGNANCY AB For patients with relapsed or refractory Hodgkin's or non-Hodgkin's lymphomas, allogeneic hematopoietic stem cell transplantation (HSCT) is a treatment option when autologous HSCT fails to achieve durable remission or is deemed inappropriate. Allogeneic HSCT can result in long-term survival even in patients with refractory lymphomas. The efficacy of allogeneic HSCT is attributed, at least in part, to an immune-mediated graft-versus-lymphoma (GVL) effect that can also be associated with significant toxicity resulting from graft-versus-host disease. However, clinical evidence of a potent GVL effect is inconsistent. Reduced-intensity conditioning before allogeneic HSCT can facilitate the use of this treatment in older patients and those at high risk. The decrease in toxicity with reduced-intensity regimens may be associated with a loss of antitumor effects. Patients with lymphoma should be selected for allogeneic HSCT on the basis of characteristics that strongly influence transplant outcomes, including histology, chemosensitivity, and donor source. C1 NCI, Canc Res Ctr, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. RP Dean, RM (reprint author), Bldg 10,Room 12N226,10 Ctr Dr,MSC 1906, Bethesda, MD 20892 USA. EM robert.dean@nih.gov NR 111 TC 3 Z9 4 U1 0 U2 0 PU CANCER INFORMATION GROUP, LP PI DALLAS PA 3535 WORTH ST, SAMMONS TOWER, STE 4802, DALLAS, TX 75246 USA SN 1526-9655 J9 CLIN LYMPHOMA JI Clin. Lymphoma PD MAR PY 2004 VL 4 IS 4 BP 238 EP 249 DI 10.3816/CLM.2004.n.004 PG 12 WC Oncology SC Oncology GA 811OH UT WOS:000220780700008 PM 15072616 ER PT J AU Walsh, TJ Groll, A Hiemenz, J Fleming, R Roilides, E Anaissie, E AF Walsh, TJ Groll, A Hiemenz, J Fleming, R Roilides, E Anaissie, E TI Infections due to emerging and uncommon medically important fungal pathogens SO CLINICAL MICROBIOLOGY AND INFECTION LA English DT Review DE emerging pathogens; fungal infections; immunocompromised ID BONE-MARROW TRANSPLANT; IN-VITRO ACTIVITY; PENICILLIUM-MARNEFFEI INFECTION; HUMAN-IMMUNODEFICIENCY-VIRUS; BLASTOSCHIZOMYCES-CAPITATUS INFECTION; TRICHODERMA-LONGIBRACHIATUM INFECTION; APIOSPERMUM PSEUDALLESCHERIA-BOYDII; TRICHOSPORON-BEIGELII INFECTION; PAECILOMYCES SPECIES INFECTIONS; LIPOSOMAL AMPHOTERICIN-B AB The emergence of less common but medically important fungal pathogens contributes to the rate of morbidity and mortality, especially in the increasingly expanding population of immunocompromised patients. These pathogens include septate filamentous fungi (e.g., Fusarium spp., Scedosporium spp., Trichoderma spp.), nonseptate Zygomycetes, the endemic dimorphic pathogen Penicillium marneffei, and non-Cryptococcus, non-Candida pathogenic yeast (e.g., Trichosporon spp.). The medical community is thus called upon to acquire an understanding of the microbiology, epidemiology and pathogenesis of these previously uncommon pathogens in order to become familiar with the options for prevention and treatment. C1 NCI, Immunocompromised Host Sect, Pediat Oncol Branch, Bethesda, MD 20892 USA. Wilhelms Univ Med Ctr, Div Pediat Hematol Oncol, Munster, Germany. Med Coll Georgia, Div Hematol Oncol, Augusta, GA 30912 USA. Boston Univ, Med Ctr, Div Infect Dis, Boston, MA USA. Univ Thessaloniki, Dept Pediat, GR-54006 Thessaloniki, Greece. Univ Arkansas Med Sci, Myeloma & Transplantat Res Ctr, Little Rock, AR 72205 USA. RP Walsh, TJ (reprint author), NCI, Immunocompromised Host Sect, Pediat Oncol Branch, Bldg 10,Room 13 N240,9000 Rockville Pike, Bethesda, MD 20892 USA. EM walsht@mail.nih.gov NR 174 TC 296 Z9 322 U1 7 U2 29 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 1198-743X J9 CLIN MICROBIOL INFEC JI Clin. Microbiol. Infect. PD MAR PY 2004 VL 10 SU 1 BP 48 EP 66 DI 10.1111/j.1470-9465.2004.00839.x PG 19 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA 803UW UT WOS:000220257000006 PM 14748802 ER PT J AU Menon, V Wang, X Greene, I Beck, GJ Kusek, JW Marcovina, SM Levey, AS Sarnak, MJ AF Menon, V Wang, X Greene, I Beck, GJ Kusek, JW Marcovina, SM Levey, AS Sarnak, MJ TI Factors associated with serum leptin in patients with chronic kidney disease SO CLINICAL NEPHROLOGY LA English DT Article DE chronic kidney disease; glomerular filtration rate; leptin; C-reactive protein ID CHRONIC-RENAL-FAILURE; AMBULATORY PERITONEAL-DIALYSIS; C-REACTIVE PROTEIN; BODY-FAT CONTENT; PLASMA LEPTIN; HEMODIALYSIS-PATIENTS; MALNUTRITION; HYPERLEPTINEMIA; INFLAMMATION; EXPRESSION AB Background and aims: Serum leptin levels are elevated in patients with kidney failure. Data on the associations of serum leptin and on the relationship of leptin with both kidney function and inflammation, are limited in patients with reduced glomerular filtration rate (GFR). We evaluated the independent associations of serum leptin in patients with reduced GFR. Material and methods: Serum leptin and C-reactive protein (CRP) were measured in samples from 798 participants of the Modification of Diet in Renal Disease Study. Multivariable analysis was used to evaluate the independent effects of kidney function and CRP on leptin levels. Results: Median (interquartile range) of serum leptin was 9.1 ng/ml (14.0). Female gender, higher percent body fat, higher insulin levels, older age, lower GFR and higher CRP were associated with higher serum leptin levels and explained 51% of the variability in the logarithm of serum leptin levels. After adjusting for the other variables, a 10 ml/min/1.73 m(2) lower GFR was associated with 6% higher mean serum leptin levels. Percent body fat and gender, explained 45% of the variability in serum leptin levels. Conclusions: Level of kidney function and CRP are associated with serum leptin in patients with reduced GFR. However, there is a stronger association between serum leptin and indices of body fat and gender in patients in the earlier stages of chronic kidney disease. 50% of the variability remains unexplained in patients with reduced GFR. C1 Tufts New England Med Ctr, Dept Med, Div Nephrol, Boston, MA 02111 USA. Tufts New England Med Ctr, Dept Med, Div Clin Care Res, Boston, MA 02111 USA. Cleveland Clin Fdn, Dept Biostat & Epidemiol, Cleveland, OH 44195 USA. NIH, Bethesda, MD 20892 USA. Univ Washington, Sch Med, NW Lipid Res Labs, Seattle, WA USA. RP Sarnak, MJ (reprint author), Tufts New England Med Ctr, Dept Med, Div Nephrol, 750 Washington St,NEMC 391, Boston, MA 02111 USA. EM msarnak@tufts-nemc.org FU NIDDK NIH HHS [1 K23 DK02904, UO1 DK 35073] NR 32 TC 11 Z9 16 U1 0 U2 0 PU DUSTRI-VERLAG DR KARL FEISTLE PI OBERHACHING PA BAJUWARENRING 4, D-82041 OBERHACHING, GERMANY SN 0301-0430 J9 CLIN NEPHROL JI Clin. Nephrol. PD MAR PY 2004 VL 61 IS 3 BP 163 EP 169 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 779MN UT WOS:000189304500001 PM 15077866 ER PT J AU Tsipouri, V Curtin, JA Nolan, PM Vizor, L Parsons, CA Clapham, CM Latham, ID Rooke, LJ Martin, JE Peters, J Hunter, AJ Rogers, D Rastan, S Brown, SDM Fisher, EMC Spurr, NK Gray, IC AF Tsipouri, V Curtin, JA Nolan, PM Vizor, L Parsons, CA Clapham, CM Latham, ID Rooke, LJ Martin, JE Peters, J Hunter, AJ Rogers, D Rastan, S Brown, SDM Fisher, EMC Spurr, NK Gray, IC TI Three novel pigmentation mutants generated by genome-wide random ENU mutagenesis in the mouse SO COMPARATIVE AND FUNCTIONAL GENOMICS LA English DT Article DE mouse; pigmentation mutant; ethylnitrosourea; mutagenesis; linkage ID GENE-FUNCTION; MICE; MIGRATION; MUTATION; DISEASE AB Three mutant mice with pigmentation phenotypes were recovered from a genomewide random mouse chemical mutagenesis study. White toes (Whto; MGI:1861986), Belly spot and white toes (Bswt; MGI:2152776) and Dark footpads 2 (Dfp2; MGI:1861991) were identified following visual inspection of progeny from a male exposed to the point mutagen ethylnitrosourea (ENU). In order to rapidly localize the causative mutations, genome-wide linkage scans were performed on pooled DNA samples from backcross animals for each mutant line. Whto was mapped to proximal mouse chromosome (Mmu) 7 between Cen (the centromere) and D7Mit112 (8.0 cM from the centromere), Bswt was mapped to centric Mmul between D1MU214 (32.1 cM) and D1Mit480 (32.8 cM) and Dfp2 was mapped to proximal Mmu4 between Cen and D4Mit18 (5.2 cM). Whto, Bswt and Dfp2 may provide novel starting points in furthering the elucidation of genetic and biochemical pathways relevant to pigmentation and associated biological processes. Copyright (C) 2004 John Wiley Sons, Ltd. C1 GlaxoSmithKline Pharmaceut, Harlow CM19 5AW, Essex, England. Univ London Imperial Coll Sci & Technol, Dept Neurogenet, London W2 1PG, England. MRC, Mammalian Genet Unit, Didcot OX11 0RD, Oxon, England. Mouse Genome Ctr, Didcot OX11 0RD, Oxon, England. Univ London Queen Mary & Westfield Coll, Dept Histopathol, London E1 4NS, England. RP Tsipouri, V (reprint author), NHGRI, NIH, Bethesda, MD 20892 USA. EM vtsip@mail.nih.gov OI Nolan, Patrick/0000-0001-5550-0334; Curtin, John/0000-0001-6299-9110 NR 20 TC 1 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1531-6912 J9 COMP FUNCT GENOM JI Compar. Funct. Genom. PD MAR PY 2004 VL 5 IS 2 BP 123 EP 127 DI 10.1002/cfg.382 PG 5 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 825UK UT WOS:000221783700002 PM 18629060 ER PT J AU Medjahed, D Lemkin, PF Smythers, GW Munroe, DJ AF Medjahed, D Lemkin, PF Smythers, GW Munroe, DJ TI Looking for cancer clues in publicly accessible databases SO COMPARATIVE AND FUNCTIONAL GENOMICS LA English DT Review DE cancer pathways; TMAP; VIRTUAL2D ID 2-DIMENSIONAL ELECTROPHORESIS; PROTEOMICS; EXPRESSION; PROTEINS AB What started out as a mere attempt to tentatively identify proteins in experimental cancer-related 2D-PAGE maps developed into VIRTUAL2D, a web-accessible repository for theoretical pI/MW charts for 92 organisms. Using publicly available expression data, we developed a collection of tissue-specific plots based on differential gene expression between normal and diseased states. We use this comparative cancer proteomics knowledge base, known as the tissue molecular anatomy project (TMAP), to uncover threads of cancer markers common to several types of cancer and to relate this information to established biological pathways. Published in 2004 by John Wiley Sons, Ltd. C1 NCI, SAIC, Lab Mol Technol, Frederick, MD 21701 USA. Sci Applicat Int Corp, Frederick, MD USA. RP Medjahed, D (reprint author), NCI, SAIC, Lab Mol Technol, 915 Tollhouse Ave,Suite 211,POB B, Frederick, MD 21701 USA. EM medjahed@ncifcrf.gov NR 7 TC 2 Z9 2 U1 1 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1531-6912 J9 COMP FUNCT GENOM JI Compar. Funct. Genom. PD MAR PY 2004 VL 5 IS 2 BP 196 EP 200 DI 10.1002/cfg.378 PG 5 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 825UK UT WOS:000221783700011 PM 18629065 ER PT J AU Stewart, JM Blakely, JA Karpowicz, PA Kalanxhi, E Thatcher, BJ Martin, BM AF Stewart, JM Blakely, JA Karpowicz, PA Kalanxhi, E Thatcher, BJ Martin, BM TI Unusually weak oxygen binding, physical properties, partial sequence, autoxidation rate and a potential phosphorylation site of beluga whale (Delphinapterus leucas) myoglobin SO COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY B-BIOCHEMISTRY & MOLECULAR BIOLOGY LA English DT Article DE beluga; myoglobin; phylogeny oxygen binding; autoxidation; Delphinapterus leucas; phosphorylation ID PLASMA LACTATE; WHITE WHALES; MUSCLE; OXYMYOGLOBIN; SPECTROSCOPY; METABOLISM; ENZYMES; ACIDS AB We purified myoglobin from beluga whale (Delphinapterus leucas) muscle (longissimus dorsi) with size exclusion and cation exchange chromatographies. The molecular mass was determined by mass spectrometry (17, 081 Da) and the isoelectric pH (9.4) by capillary isoelectric focusing. The near-complete amino acid sequence was determined and a phylogeny indicated that beluga was in the same clad as Dall's and harbor porpoises. There were consensus motifs for a phosphorylation site on the protein surface with the most likely site at serine-117. This motif was common to all cetacean myoglobins examined. Two oxygen-binding studies at 37 degreesC indicated dissociation constants (20.5 and 23.6 muM) 5.7-6.6 times larger than horse myoglobin (3.6 muM). The autoxidation rate of beluga myoglobin at 37 degreesC, pH 7.2 was 0.218+/-0.028 h(-1), 1/3 larger than reported for myoglobin of terrestrial mammals. There was no clear sequence change to explain the difference in oxygen binding or autoxidation although substitutions (N66 and T67) in an invariant rich sequence (HGNTV) distal to the heme may play a role. Structural models based on the protein sequence and constructed on topologies of known templates (horse and sperm whale crystal structures) were not adequate to assess perturbation of the heme pocket. (C) 2004 Elsevier Inc. All rights reserved. C1 Mt Allison Univ, Dept Biol, Biochem Programme, Sackville, NB E4L 1G7, Canada. Prot Solut, Stratford, ON N5A 7P6, Canada. NIMH, Lab Neurotoxicol, NIH, Bethesda, MD 20892 USA. RP Stewart, JM (reprint author), Mt Allison Univ, Dept Biol, Biochem Programme, Flemingon Bldg,63B York St, Sackville, NB E4L 1G7, Canada. EM jstewart@mta.ca RI Karpowicz, Phillip/C-3334-2016; OI Stewart, John/0000-0003-3116-4174 NR 25 TC 15 Z9 17 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1096-4959 J9 COMP BIOCHEM PHYS B JI Comp. Biochem. Physiol. B-Biochem. Mol. Biol. PD MAR PY 2004 VL 137 IS 3 BP 401 EP 412 DI 10.1016/j.cbpc.2003.01.007 PG 12 WC Biochemistry & Molecular Biology; Zoology SC Biochemistry & Molecular Biology; Zoology GA 810CD UT WOS:000220681500012 PM 15050527 ER PT J AU Goulding, DR Blankenship-Paris, TL Lewbart, GA Myers, PH Demianenko, TK Clark, JA Forsythe, DB AF Goulding, DR Blankenship-Paris, TL Lewbart, GA Myers, PH Demianenko, TK Clark, JA Forsythe, DB TI Gill trematodes (flukes) in wild-caught killifish (Fundulus heteroclitus) SO CONTEMPORARY TOPICS IN LABORATORY ANIMAL SCIENCE LA English DT Article ID BEHAVIOR AB Three wild caught killifish (Fundulus heteroclitus) on an Institutional Animal Care and Use Committee-approved protocol were found dead within 2 days after being received. The fish were housed in two separate aquaria. Aquarium water was evaluated, and pH, salinity, ammonia, nitrate, and nitrite levels were within acceptable parameters. Several remaining fish appeared to be slow-moving and were presented for necropsy. Multiple, scattered, ulcerated skin lesions (diameter, 1 to 5 mm) were noted at necropsy and were cultured. No pathogenic bacteria were isolated. Wet-mount samples of the gills revealed multiple cysts at the gill margins, each containing a motile organism. No other gill parasites were detected. A diagnosis of trematodiasis was made. The cysts were identified as encysted metacercariae of a digenetic trematode. We surmise that the large numbers of gill flukes combined with the stress of recent shipment likely caused the observed morbidity and mortality. C1 NIEHS, Comparat Med Branch, Res Triangle Pk, NC 27709 USA. N Carolina State Univ, Coll Vet Med, Dept Clin Sci, Raleigh, NC 27606 USA. RP Goulding, DR (reprint author), NIEHS, Comparat Med Branch, MD C1-06, Res Triangle Pk, NC 27709 USA. NR 9 TC 1 Z9 1 U1 0 U2 2 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1060-0558 J9 CONTEMP TOP LAB ANIM JI Contemp. Top. Lab. Anim. Sci. PD MAR PY 2004 VL 43 IS 2 BP 32 EP 34 PG 3 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 804NB UT WOS:000220304300008 PM 15053506 ER PT J AU Silverman, HJ Miller, FG AF Silverman, HJ Miller, FG TI Control group selection in critical care randomized controlled trials evaluating interventional strategies: An ethical assessment SO CRITICAL CARE MEDICINE LA English DT Review DE research ethics; human experimentation; critical care; human subject protection; research subjects ID ACUTE LUNG INJURY; RESPIRATORY-DISTRESS-SYNDROME; TIDAL VOLUMES; ILL PATIENTS; CLINICAL-TRIALS; METAANALYSIS; DESIGN; VENTILATION; THERAPY; SEPSIS AB Background: Ethical concern has been raised with critical care randomized controlled trials in which the standard of care reflects a broad range of clinical practices. Commentators have argued that trials without an unrestricted control group, in which standard practices are implemented at the discretion of the attending physician, lack the ability to redefine the standard of care and might expose subjects to excessive harms due to an inability to stop early. Objective: To develop a framework for analyzing control group selection for critical care trials. Method: Ethical analysis. Results: A key ethical variable in trial design is the extent with which the control group adequately reflects standard care practices. Such a control group might incorporate either the "unrestricted" practices of physicians or a protocol that specifies and restricts the parameters of standard practices. Control group selection should be determined with respect to the following ethical objectives of trial design: 1) clinical value, 2) scientific validity, 3) efficiency and feasibility, and 4) protection of human subjects. Because these objectives may conflict, control group selection will involve trade-offs and compromises. Trials using a protocolized rather than an unrestricted standard care control group will likely have enhanced validity. However, if the protocolized control group lacks representativeness to standard care practices, then trials that use such groups will offer less clinical value and could provide less assurance of protecting subjects compared with trials that use unrestricted control groups. For trials evaluating contrasting strategies that do not adequately represent standard practices, use of a third group that is more representative of standard practices will enhance clinical value and increase the ability to stop early if needed to protect subjects. These advantages might come at the expense of efficiency and feasibility. Conclusion: Weighing and balancing the competing ethical objectives of trial design should be done for each trial. C1 Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA. NIH, Dept Clin Bioeth, Bethesda, MD 20892 USA. RP Silverman, HJ (reprint author), Univ Maryland, Sch Med, Dept Med, 10 S Pine St,Suite 800, Baltimore, MD 21201 USA. EM hsilverm@medicine.umaryland.edu NR 35 TC 38 Z9 39 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD MAR PY 2004 VL 32 IS 3 BP 852 EP 857 DI 10.1097/01.CCM.0000114814.62759.06 PG 6 WC Critical Care Medicine SC General & Internal Medicine GA 805MA UT WOS:000220369200036 PM 15090973 ER PT J AU Ward, MM AF Ward, MM TI Patient-centered care and health outcomes SO CURRENT OPINION IN RHEUMATOLOGY LA English DT Review C1 NIAMS, Intramural Res Program, NIH, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Ward, MM (reprint author), NIAMS, Intramural Res Program, NIH, US Dept Hlth & Human Serv, Bldg 10,Room 9S205,10 Ctr Dr,MSC 1828, Bethesda, MD 20892 USA. EM wardm1@mail.nih.gov NR 6 TC 8 Z9 8 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8711 J9 CURR OPIN RHEUMATOL JI CURR. OPIN. RHEUMATOL. PD MAR PY 2004 VL 16 IS 2 BP 89 EP 90 DI 10.1097/00002281-200403000-00002 PG 2 WC Rheumatology SC Rheumatology GA 779FV UT WOS:000189285400001 PM 14770090 ER PT J AU Ward, MM AF Ward, MM TI Outcome measurement: health status and quality of life SO CURRENT OPINION IN RHEUMATOLOGY LA English DT Review DE outcome measures; health status; health-related quality of life; pain; arthritis ID OSTEOARTHRITIS HAND INDEX; RHEUMATOID-ARTHRITIS; ANKYLOSING-SPONDYLITIS; ASSESSMENT QUESTIONNAIRE; KNEE OSTEOARTHRITIS; CONSTRUCT-VALIDITY; CLINICAL-PRACTICE; RATING-SCALE; RESPONSIVENESS; RELIABILITY AB Measures of health-related quality of life, which assess patients' symptoms, their functioning, and their satisfaction with their health status, have received increased attention. Quality-of-life measures specifically developed for patients with rheumatoid arthritis and ankylosing spondylitis have been reported, and generic quality-of-life measures have been validated in patients with diverse rheumatic diseases. Although many studies have assessed the psychometric properties of health status measures, few studies have focused on the interpretation and meaning of questionnaire results. New measures should identify the unique role they occupy in patient assessment. C1 NIAMS, Intramural Res Program, NIH, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Ward, MM (reprint author), NIAMS, Intramural Res Program, NIH, US Dept Hlth & Human Serv, Bldg 10,Room 9S205,10 Ctr Dr,MSC 1828, Bethesda, MD 20892 USA. EM wardm1@mail.nih.gov NR 51 TC 18 Z9 23 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8711 J9 CURR OPIN RHEUMATOL JI CURR. OPIN. RHEUMATOL. PD MAR PY 2004 VL 16 IS 2 BP 96 EP 101 DI 10.1097/00002281-200403000-00004 PG 6 WC Rheumatology SC Rheumatology GA 779FV UT WOS:000189285400003 PM 14770092 ER PT J AU Iida, T Lilly, MA AF Iida, T Lilly, MA TI missing oocyte encodes a highly conserved nuclear protein required for the maintenance of the meiotic cycle and oocyte identity in Drosophila SO DEVELOPMENT LA English DT Article DE meiosis; oogenesis; Drosophila; synaptonemal complex; oocyte differentiation ID BIC-D; OOGENESIS; GENE; DIFFERENTIATION; MELANOGASTER; ORB; RECOMBINATION; GERMLINE; MEIOSIS; SPECIFICATION AB In Drosophila, a single oocyte develops within a 16-cell germline cyst. Although all 16 cells initiate meiosis and undergo premeiotic S phase, only the oocyte retains its meiotic chromosome configuration and remains in the meiotic cycle. The other 15 cells in the cyst enter the endocycle and develop as polyploid nurse cells. A longstanding goal in the field has been to identify factors that are concentrated or activated in the oocyte, that promote meiotic progression and/or the establishment of the oocyte identity. We present the characterization of the missing oocyte gene, an excellent candidate for a gene directly involved in the differentiation of the oocyte nucleus. The missing oocyte gene encodes a highly conserved protein that preferentially accumulates in pro-oocyte nuclei in early prophase of meiosis 1. In missing oocyte mutants, the oocyte enters the endocycle and develops as a polyploid nurse cell. Genetic interaction studies indicate that missing oocyte influences meiotic progression prior to pachytene and may interact with pathways that control DNA metabolism. Our data strongly suggest that the product of the missing oocyte gene acts in the oocyte nucleus to facilitate the execution of the unique cell cycle and developmental programs that produce the mature haploid gamete. C1 NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Lilly, MA (reprint author), NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. EM mlilly@helix.nih.gov OI Lilly, Mary/0000-0003-1564-619X NR 48 TC 16 Z9 18 U1 0 U2 4 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD MAR PY 2004 VL 131 IS 5 BP 1029 EP 1039 DI 10.1242/dev.01001 PG 11 WC Developmental Biology SC Developmental Biology GA 805HS UT WOS:000220358000007 PM 14973288 ER PT J AU Meyer, SE Carlson, GA Wiggs, EA Martinez, PE Ronsaville, DS Klimes-Dougan, B Gold, PW Radke-Yarrow, M AF Meyer, SE Carlson, GA Wiggs, EA Martinez, PE Ronsaville, DS Klimes-Dougan, B Gold, PW Radke-Yarrow, M TI A prospective study of the association among impaired executive functioning, childhood attentional problems, and the development of bipolar disorder SO DEVELOPMENT AND PSYCHOPATHOLOGY LA English DT Article ID CARD SORTING TEST; DEFICIT-HYPERACTIVITY DISORDER; MANIC-DEPRESSIVE ILLNESS; DORSOLATERAL PREFRONTAL CORTEX; POSITRON EMISSION TOMOGRAPHY; FRONTAL-LOBE FUNCTIONS; NEUROPSYCHOLOGICAL FUNCTION; DIAGNOSTIC INTERVIEW; TEST-PERFORMANCE; SCHIZOPHRENIA AB Studies of adults who have been diagnosed with, and treated for, bipolar disorder have shown that these patients exhibit impairment on measures of executive functioning. However, it is unclear whether executive dysfunction precedes the diagnosis of bipolar illness, or develops subsequent to its onset. Moreover, investigators have failed to control for the effects of premorbid attentional problems on cognitive performance in these patients. The present authors explored these questions using data from a longitudinal prospective study of individuals at risk for major mood disorder. Results revealed that 67% of participants who met criteria for bipolar disorder in young adulthood showed impairment on the Wisconsin Card Sorting Test (WCST) when they were assessed during adolescence, as compared with 17% of individuals with no major mood diagnosis, and 19% with unipolar depression. This association between performance on the WCST and bipolar illness was not accounted for by high rates of premorbid attentional disturbance. In fact, among participants with early attentional problems, only those who ultimately developed bipolar disorder exhibited impairment on the WCST. Early attentional problems that preceded unipolar depression or no mood disorder were not associated with executive dysfunction. C1 Univ Calif Los Angeles, Neuropsychiat Inst & Hosp, Los Angeles, CA 90024 USA. Univ Minnesota, Minneapolis, MN 55455 USA. NIMH, Bethesda, MD 20892 USA. SUNY Stony Brook, Stony Brook, NY 11794 USA. Catholic Univ Amer, Washington, DC 20064 USA. RP Meyer, SE (reprint author), Univ Calif Los Angeles, Neuropsychiat Inst & Hosp, 760 Westwood Plaza,Room 48-241, Los Angeles, CA 90024 USA. EM semeyer@mednet.ucla.edu NR 63 TC 88 Z9 90 U1 6 U2 19 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4211 USA SN 0954-5794 J9 DEV PSYCHOPATHOL JI Dev. Psychopathol. PD SPR PY 2004 VL 16 IS 2 BP 461 EP 476 DI 10.1017/S095457940404461X PG 16 WC Psychology, Developmental SC Psychology GA 849XM UT WOS:000223574900013 PM 15487606 ER PT J AU Kalinowski, RR Berlot, CH Jones, TLZ Ross, LF Jaffe, LA Mehlmann, LM AF Kalinowski, RR Berlot, CH Jones, TLZ Ross, LF Jaffe, LA Mehlmann, LM TI Maintenance of meiotic prophase arrest in vertebrate oocytes by a G(s) protein-mediated pathway SO DEVELOPMENTAL BIOLOGY LA English DT Article DE meiotic prophase arrest; oocyte maturation; heterotrimeric G proteins; zebrafish; Xenopus; mouse ID BETA-GAMMA-SUBUNITS; FOLLICLE-STIMULATING-HORMONE; XENOPUS-LAEVIS OOCYTES; ADENYLYL-CYCLASE; PROGESTERONE-RECEPTOR; MOUSE OOCYTES; DEPENDENT ACTIVATION; MOLECULAR-CLONING; COUPLED RECEPTORS; BRACHYDANIO-RERIO AB Maintenance of meiotic prophase arrest in fully grown vertebrate oocytes depends on an elevated level of cAMP in the oocyte. To investigate how the cAMP level is regulated, we examined whether the activity of an oocyte G protein of the family that stimulates adenylyl cyclase, G(s) is required to maintain meiotic arrest. Microinjection of a dominant negative form of G(s) into Xenopus and mouse oocytes, or microinjection of an antibody that inhibits the G(s) G protein into zebrafish oocytes, caused meiosis to resume. Together with previous studies, these results support the conclusion that G(s)-regulated generation of cAMP by the oocyte is a common mechanism for maintaining meiotic prophase arrest in vertebrate oocytes. (C) 2003 Elsevier Inc. All rights reserved. C1 Univ Connecticut, Ctr Hlth, Dept Cell Biol, Farmington, CT 06032 USA. Geisinger Med Clin, Weis Ctr Res, Danville, PA 17822 USA. NIDDKD, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. RP Mehlmann, LM (reprint author), Univ Connecticut, Ctr Hlth, Dept Cell Biol, Farmington, CT 06032 USA. EM bkalinowski@neuron.uchc.edu; chberlot@geisinger.edu; tlzj@helix.nih.gov; lross@neuron.uchc.edu; ljaffe@neuron.uchc.edu; lmehlman@neuron.uchc.edu NR 75 TC 52 Z9 57 U1 2 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD MAR 1 PY 2004 VL 267 IS 1 BP 1 EP 13 DI 10.1016/j.ydbio.2003.11.011 PG 13 WC Developmental Biology SC Developmental Biology GA 779CU UT WOS:000189278700001 PM 14975713 ER PT J AU Liu, CQ Knezevic, V Mackem, S AF Liu, CQ Knezevic, V Mackem, S TI Ventral tail bud mesenchyme is a signaling center for tail paraxial mesoderm induction SO DEVELOPMENTAL DYNAMICS LA English DT Article DE paraxial mesoderm; mesoderm induction; ventral tail bud mesenchyme; ventral ectodermal ridge (VER); signaling center; chick embryo ID T-BOX GENES; CHICK-EMBRYO; PRIMITIVE STREAK; XENOPUS-LAEVIS; VERTEBRATE EMBRYO; ECTODERMAL RIDGE; NEURAL INDUCTION; POSTERIOR REGION; CELL MOVEMENTS; HOMEOBOX GENE AB A large body of evidence from several systems indicates that formation of the vertebrate tail is morphogenetically continuous with gastrulation, including neural inducing activity in descendants of the gastrula organizer. However, the signaling centers and molecular events regulating tail mesoderm induction and its organized elongation remain poorly defined. In mammals, the ventral ectoderm ridge (VER) is essential to maintain ongoing formation of paraxial mesoderm and somitogenesis in cultures of intact tail. Avian tail buds contain a similar VER structure. Here, we report that the chick ventral tail bud operates as a signaling center for paraxial mesoderm induction. By using "organizer" style grafting assays to early host embryos, we found that ventral tail bud was able to induce elongated paraxial mesodermal extensions and that the ventral tail bud mesenchyme underlying the VER is both necessary and sufficient for the induction in this assay system. Our observations combined with those of others suggest that interplay between several different signaling centers in the amniote tail bud regulates the coordinate induction and elongation of axial and paraxial structures in the developing tail. Developmental Dynamics 229-600-606, 2004. Published 2004 Wiley-Liss, Inc.dagger C1 NCI, Ctr Canc Res, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Mackem, S (reprint author), NCI, Ctr Canc Res, Pathol Lab, NIH, Bldg 10-Room 2A33, Bethesda, MD 20892 USA. EM smack@helix.nih.gov RI Liu, Chunqiao/O-3391-2013 OI Liu, Chunqiao/0000-0002-0299-7401 FU NICHD NIH HHS [N01 HD-7-3263] NR 44 TC 8 Z9 8 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 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD MAR PY 2004 VL 229 IS 3 BP 600 EP 606 DI 10.1002/dvdy.20017 PG 7 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 780EP UT WOS:000189359600021 PM 14991715 ER PT J AU Cordon, IM Pipe, ME Sayfan, L Melinder, A Goodman, GS AF Cordon, IM Pipe, ME Sayfan, L Melinder, A Goodman, GS TI Memory for traumatic experiences in early childhood SO DEVELOPMENTAL REVIEW LA English DT Review DE memory; development; trauma; children; infancy; infantile amnesia ID POSTTRAUMATIC-STRESS-DISORDER; LONG-TERM RECALL; CHILDRENS MEMORY; EXPLICIT MEMORY; INFANT MEMORY; AUTOBIOGRAPHICAL MEMORY; EYEWITNESS MEMORY; IMPLICIT MEMORY; COGNITIVE NEUROSCIENCE; AMYGDALA STIMULATION AB Traumatic experiences in early childhood raise important questions about memory development in general and about the durability and accessibility of memories for traumatic events in particular. We discuss memory for early childhood traumatic events, from a developmental perspective, focusing on those factors that may equally influence memories for both traumatic and non-traumatic events and those factors that may uniquely affect memories of traumatic events and possibly memory development generally. To obtain a more complete understanding of trauma-related memory, we draw on both the scientific and clinical literatures. These literatures indicate commonalities across memories for traumatic and non-traumatic events as well as potentially unique influences on trauma memory. (C) 2003 Elsevier Inc. All rights reserved. C1 Univ Calif Davis, Davis, CA 95616 USA. NICHHD, Bethesda, MD 20892 USA. Univ Oslo, N-0316 Oslo, Norway. RP Goodman, GS (reprint author), Univ Calif Davis, Davis, CA 95616 USA. EM ggoodman@ucdavis.edu NR 207 TC 51 Z9 52 U1 1 U2 16 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0273-2297 J9 DEV REV JI Dev. Rev. PD MAR PY 2004 VL 24 IS 1 BP 101 EP 132 DI 10.1016/j.dr.2003.09.003 PG 32 WC Psychology, Developmental SC Psychology GA 771XG UT WOS:000188810900005 ER PT J AU Yan, LZ Figueroa, DJ Austin, CP Liu, Y Bugianesi, RM Slaughter, RS Kaczorowski, GJ Kohler, MG AF Yan, LZ Figueroa, DJ Austin, CP Liu, Y Bugianesi, RM Slaughter, RS Kaczorowski, GJ Kohler, MG TI Expression of voltage-gated potassium channels in human and rhesus pancreatic islets SO DIABETES LA English DT Article ID DEPENDENT K+ CHANNELS; BETA-CELLS; INSULIN-SECRETION; ALPHA-SUBUNITS; KV2.1; HYPOGLYCEMIA; CURRENTS; SULFONYLUREAS; ACTIVATION; SUBFAMILY AB Voltage-gated potassium channels (Kv channels) are involved in repolarization of excitable cells. In pancreatic beta-cells, prolongation of the action potential by block of delayed rectifier potassium channels would be expected to increase intracellular free calcium and to promote insulin release in a glucose-dependent manner. However, the specific Kv channel subtypes responsible for repolarization in beta-cells, most importantly in humans, are not completely resolved. In this study, we have investigated the expression of 26 subtypes from Kv subfamilies in human islet mRNA. The results of the RT-PCR analysis were extended by in situ hybridization and/or immunohistochemical analysis on sections from human or Rhesus pancreas. Cell-specific markers were used to show that Kv2.1, Kv3.2, Kv6.2, and Kv9.3 are expressed in beta-cells, that Kv3.1 and Kv6.1 are expressed in alpha-cells, and that Kv2.2 is expressed in delta-cells. This study suggests that more than one Kv channel subtype might contribute to the beta-cell delayed rectifier current and that this current could be formed by heterotetramers of active and silent subunits. C1 Merck Res Labs, Dept Ion Channels, Rahway, NJ 07065 USA. Merck Res Labs, Dept Mol & Invest Toxicol, W Point, PA USA. Merck Res Labs, Dept Neurosci, W Point, PA USA. NHGRI, Bethesda, MD 20892 USA. Merck Res Labs, Dept Bioinformat, W Point, PA USA. RP Yan, LZ (reprint author), Merck Res Labs, Dept Ion Channels, RY80N-C31, Rahway, NJ 07065 USA. EM lizhen_yan@merek.com; martin_kohler@merck.com NR 54 TC 60 Z9 63 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD MAR PY 2004 VL 53 IS 3 BP 597 EP 607 DI 10.2337/diabetes.53.3.597 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 779NV UT WOS:000189307500012 PM 14988243 ER PT J AU de Courten, BV Weyer, C Stefan, N Horton, M DelParigi, A Havel, P Bogardus, C Tataranni, PA AF de Courten, BV Weyer, C Stefan, N Horton, M DelParigi, A Havel, P Bogardus, C Tataranni, PA TI Parasympathetic blockade attenuates augmented pancreatic polypeptide but not insulin secretion in Pima Indians SO DIABETES LA English DT Article ID PARACETAMOL ABSORPTION TEST; NERVOUS-SYSTEM; OBESE; HYPERINSULINEMIA; RESISTANCE; VAGAL; POPULATION; RISK; STIMULATION; DYSFUNCTION AB There is evidence from animal models of obesity and type 2 diabetes that increased parasympathetic vagal input to the pancreas contributes to hyperinsulinemia. Compared with Caucasians, Pima Indians have a high risk of type 2 diabetes And exhibit marked hiperinsulinemia and elevated plasma levels of pancreatic polypeptide (PP), an islet hormone considered a surrogate marker of parasympathetic nervous system (PNS) drive to the pancreas. To test if hyperinsulinemia in Pima Indians is due to increased vagal input to the beta-cell, we examined the effect of PNS blockade in 17 Caucasian (aged 35 +/- 8 years, body fat 23 +/- 7% [mean +/- SD]) and 17 Pima Indian males (aged 28 +/- 8 years, body fat 29 +/- 5%) with normal glucose tolerance. Each participant underwent four consecutive standardized liquid meal tests (64% carbohydrate, 22% fat, and 14% protein) during which a primed infusion of atropine was administered for 120 min at the following doses: 0, 2.5, 5, and 10 mug . kg fat-free mass (FFM)(-1) . h(-1). Areas under the curve for early (AUC(0-30 min)) and total (AUC(0-120 min)) postprandial insulin and PP secretory responses ere calculated. Early postprandial insulin and PP secretory responses were higher in Pima Indians compared with those of Caucasians (both P = 0.01). Secretion of insulin and PP was inhibited by atropine (both P < 0.001). Increasing doses of atropine attenuated the ethnic difference in PP (P = 0.01) but not in early insulin secretory responses (P = 0.6),an effect that was not due to differences in gastric emptying rate (acetaminophen test) and/or circulating glucose. Similar results were observed for total secretory responses. These results confirm that compared with Caucasians, Pima Indians have an exaggerated PNS drive to pancreatic F-cells that secrete PP. However, the hyperinsulinemia of this population does not appear to be due to increased vagal input to pancreatic beta-cells. C1 NIDDKD, Clin Diabet & Nutr Sect, NIH, Phoenix, AZ 85016 USA. Phoenix Indian Med Ctr, Dept Ophthalmol, Phoenix, AZ USA. Univ Calif Davis, Dept Nutr, Davis, CA 95616 USA. RP Tataranni, PA (reprint author), NIDDKD, Clin Diabet & Nutr Sect, NIH, 4212 N 16th St,Rm 5-41, Phoenix, AZ 85016 USA. EM antoniot@mail.nih.gov OI de Courten, Barbora/0000-0001-8760-2511 NR 32 TC 18 Z9 18 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 EI 1939-327X J9 DIABETES JI Diabetes PD MAR PY 2004 VL 53 IS 3 BP 663 EP 671 DI 10.2337/diabetes.53.3.663 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 779NV UT WOS:000189307500019 ER PT J AU Schmidt, R Laurier, LJ Nilsson, LG Pajak, A Sans, S Berger, K Breteler, MM de Ridder, M Dufouil, C Fuhrer, R Giampaoli, S Hofman, A AF Schmidt, R Laurier, LJ Nilsson, LG Pajak, A Sans, S Berger, K Breteler, MM de Ridder, M Dufouil, C Fuhrer, R Giampaoli, S Hofman, A CA CASCADE Consortium TI Magnetic resonance imaging of the brain in diabetes - The Cardiovascular Determinants of Dementia (CASCADE) study SO DIABETES LA English DT Article ID WHITE-MATTER HYPERINTENSITIES; AUSTRIAN STROKE PREVENTION; ELDERLY-PEOPLE; BLOOD-PRESSURE; RISK-FACTORS; ALZHEIMERS-DISEASE; HEALTH; MRI; MELLITUS; POPULATION AB Diabetic patients are at increased risk for stroke, but little is known about the presence of other brain lesions. We studied the association of magnetic resonance imaging-detected brain lesions to diabetes in 1,252 individuals aged 65-75 years who were randomly selected from eight European population registries or defined working populations. All scans were centrally read for brain abnormalities, including infarcts, white matter lesions, and atrophy. We used a three-point scale to rate periventricular white matter lesions, and the volume of subcortical lesions was calculated according to their number and size. Subjective grading of cortical atrophy by lobe and summation of the lobar grades resulted in a total cortical atrophy score. The mean of three linear measurements of the ventricular diameter relative to the intracranial cavity defined the severity of subcortical atrophy. After adjustment for possible confounders, diabetes was associated with cortical brain atrophy but not with any focal brain lesions or subcortical atrophy. There was a strong interaction of diabetes and hypertension, such that the association between diabetes and cortical atrophy existed only in hypertensive but not in normotensive participants. Cognitive and pathological data are needed to determine the clinical significance of these findings as well as to understand the mechanisms underlying these associations. C1 Med Univ Graz, Dept Neurol, A-8036 Graz, Austria. NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA. Erasmus Med Ctr, Dept Epidemiol & Biometry, Rotterdam, Netherlands. Stockholm Univ, Dept Psychol, S-10691 Stockholm, Sweden. Jagiellonian Univ, Sch Med, Inst Publ Hlth, Dept Epidemiol & Populat Studies, Krakow, Poland. Dept Hlth & Social Secur, Inst Hlth Studies, Barcelona, Spain. Univ Munster, Inst Epidemiol & Social Med, D-4400 Munster, Germany. Hop La Pitie Salpetriere, INSERM, U360, Paris, France. Univ Coll, Dept Epidemiol & Publ Hlth, London, England. Ist Super Sanita, Epidemiol & Biostat Lab, I-00161 Rome, Italy. RP Schmidt, R (reprint author), Med Univ Graz, Dept Neurol, Auenbruggerpl 22, A-8036 Graz, Austria. EM reinhold.schmidt@uni-graz.at RI Dufouil, Carole/J-4968-2012; Breteler, Monique /J-5058-2014 NR 45 TC 156 Z9 160 U1 0 U2 7 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD MAR PY 2004 VL 53 IS 3 BP 687 EP 692 DI 10.2337/diabetes.53.3.687 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 779NV UT WOS:000189307500022 PM 14988253 ER PT J AU Silander, K Scott, LJ Valle, TT Mohlke, KL Stringham, HM Wiles, KR Duren, WL Doheny, KF Pugh, EW Chines, P Narisu, N White, PP Fingerlin, TE Jackson, AU Li, C Ghosh, S Magnuson, VL Colby, K Erdos, MR Hill, JE Hollstein, P Humphreys, KM Kasad, RA Lambert, J Lazaridis, KN Lin, G Morales-Mena, A Patzkowski, K Pfahl, C Porter, R Rha, D Segal, L Suh, YD Tovar, J Unni, A Welch, C Douglas, JA Epstein, MP Hauser, ER Hagopian, W Buchanan, TA Watanabe, RM Bergman, RN Tuomilehto, J Collins, FS Boehnke, M AF Silander, K Scott, LJ Valle, TT Mohlke, KL Stringham, HM Wiles, KR Duren, WL Doheny, KF Pugh, EW Chines, P Narisu, N White, PP Fingerlin, TE Jackson, AU Li, C Ghosh, S Magnuson, VL Colby, K Erdos, MR Hill, JE Hollstein, P Humphreys, KM Kasad, RA Lambert, J Lazaridis, KN Lin, G Morales-Mena, A Patzkowski, K Pfahl, C Porter, R Rha, D Segal, L Suh, YD Tovar, J Unni, A Welch, C Douglas, JA Epstein, MP Hauser, ER Hagopian, W Buchanan, TA Watanabe, RM Bergman, RN Tuomilehto, J Collins, FS Boehnke, M TI A large set of Finnish affected sibling pair families with type 2 diabetes suggests susceptibility loci on chromosomes 6, 11, and 14 SO DIABETES LA English DT Article ID MELLITUS GENETICS FUSION; AUTOSOMAL GENOME SCAN; INSULIN-RESISTANCE; LINKAGE ANALYSIS; CALPAIN-10 GENE; SPOT-14 PROTEIN; MAPPING GENES; WIDE SEARCH; SIB PAIRS; FINLAND AB The aim of the Finland-United States Investigation of NIDDM Genetics (FUSION) study is to identify genes that predispose to type 2 diabetes or are responsible for variability in diabetes-related traits via a positional cloning and positional candidate gene approach. In a previously published genome-wide scan of 478 Finnish affected sibling pair (ASP) families (FUSION 1), the strongest linkage results were on chromosomes 20 and 11. We now report a second genome-wide scan using an independent set of 242 Finnish ASP families (FUSION 2), a detailed analysis of the combined set of 737 FUSION 1+2 families (495 updated FUSION 1 families), and fine mapping of the regions of chromosomes 11 and 20. The strongest FUSION 2 linkage results were on chromosomes 6 (maximum logarithm of odds score [MLS]=2.30 at 95 cM) and 14 (MLS=1.80 at 57 cM). For the combined FUSION 1+2 families, three results were particularly notable: chromosome 11 (MLS=2.98 at 82 cM), chromosome 14 (MLS=2.74 at 58 cM), and chromosome 6 (MLS=2.66 at 96 cM). We obtained smaller FUSION 1+2 MLSs on chromosomes X (MLS=1.27 at 152 cM) and 20p (MLS=1.21 at 20 cM). Among the 10 regions that showed nominally significant evidence for linkage in FUSION 1, four (on chromosomes 6, 11, 14, and X) also showed evidence for linkage in FUSION 2 and stronger evidence for linkage in the combined FUSION 1+2 sample. C1 Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA. NHGRI, Genome Technol Branch, Bethesda, MD 20892 USA. Natl Publ Hlth Inst, Dept Epidemiol & Hlth Promot, Diabet & Genet Epidemiol Unit, Helsinki, Finland. Natl Publ Hlth Inst, Dept Biochem, Helsinki, Finland. Johns Hopkins Sch Med, Inst Med Genet, Ctr Inherited Dis Res, Baltimore, MD USA. Pacific NW Res Inst, Seattle, WA USA. Univ So Calif, Keck Sch Med, Dept Med, Los Angeles, CA USA. Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA. Univ So Calif, Keck Sch Med, Dept Physiol & Biophys, Los Angeles, CA USA. Univ Helsinki, Dept Publ Hlth, Helsinki, Finland. RP Boehnke, M (reprint author), Univ Michigan, Sch Publ Hlth, Dept Biostat, 1420 Washington Hts, Ann Arbor, MI 48109 USA. EM boehnke@umich.edu RI Li, Chun/B-8388-2012 FU NHGRI NIH HHS [N01-HG-65403, HG00040, HG00376]; NIDDK NIH HHS [DK09525, DK27619, DK29867, DK62370, R01 DK029867]; NIOSH CDC HHS [OH95-C-N030] NR 50 TC 52 Z9 53 U1 1 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD MAR PY 2004 VL 53 IS 3 BP 821 EP 829 DI 10.2337/diabetes.53.3.821 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 779NV UT WOS:000189307500038 PM 14988269 ER PT J AU Rotimi, CN Chen, GJ Adeyemo, AA Furbert-Harris, P Guass, D Zhou, J Berg, K Adegoke, O Amoah, A Owusu, S Acheampong, J Agyenim-Boateng, K Eghan, BA Oli, J Okafor, G Ofoegbu, E Osotimehin, B Abbiyesuku, F Johnson, T Rufus, T Fasanmade, O Kittles, R Daniel, H Chen, YX Dunston, G Collins, FS AF Rotimi, CN Chen, GJ Adeyemo, AA Furbert-Harris, P Guass, D Zhou, J Berg, K Adegoke, O Amoah, A Owusu, S Acheampong, J Agyenim-Boateng, K Eghan, BA Oli, J Okafor, G Ofoegbu, E Osotimehin, B Abbiyesuku, F Johnson, T Rufus, T Fasanmade, O Kittles, R Daniel, H Chen, YX Dunston, G Collins, FS TI A genome-wide search for type 2 diabetes susceptibility genes in West Africans - The Africa America Diabetes Mellitus (AADM) study SO DIABETES LA English DT Article ID LINKAGE ANALYSIS; CHROMOSOME 20Q; PREVALENCE; LOCUS; MUTATIONS; NIDDM AB The incidence of type 2 diabetes is growing rapidly, not only in developed countries but also worldwide. We chose to study type 2 diabetes in West Africa, where diabetes is less common than in the U.S., reasoning that in an environment where calories are less abundant, incident cases of type 2 diabetes might carry a proportionately greater genetic component. Through the Africa America Diabetes Mellitus (AADM) study, we carried out a genome-wide linkage analysis of type 2 diabetes in a cohort of 343 affected sibling pairs (6911 individuals) enrolled from five West African centers in two countries (Ghana: Accra and Kumasi; Nigeria: Enugu, Ibadan, and Lagos). A total of 390 polymorphic markers were genotyped, and multipoint linkage analysis was conducted using the GENEHUNTER-PLUS and ASM programs. Suggestive evidence of linkage was observed in four regions on three chromosomes (12, 19, and 20). The two largest logarithm of odds scores of 2.63 and 1.92 for chromosomes 20q13.3 and 12q24, respectively, are particularly interesting because these regions have been reported to harbor diabetes susceptibility genes in several other populations and ethnic groups. Given the history of forced migration of West African populations during the slave trade, these results should have considerable relevance to the study of type 2 diabetes in African Americans. C1 Howard Univ, Coll Med, Natl Human Genome Ctr, Genet Epidemiol Unit,Dept Microbiol, Washington, DC 20059 USA. Univ Ibadan, Coll Med, Ibadan, Nigeria. NHGRI, NIH, Bethesda, MD 20892 USA. Univ Ghana, Sch Med, Dept Med, Accra, Ghana. Univ Sci & Technol Kumasi, Dept Med, Kumasi, Ghana. Univ Nigeria, Teaching Hosp, Dept Med, Enugu, Nigeria. Univ Lagos, Coll Med, Endocrine & Metab Unit, Lagos, Nigeria. RP Rotimi, CN (reprint author), Howard Univ, Coll Med, Natl Human Genome Ctr, Genet Epidemiol Unit,Dept Microbiol, 2216 6th St NW, Washington, DC 20059 USA. EM crotimi@howard.edu NR 21 TC 46 Z9 47 U1 0 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD MAR PY 2004 VL 53 IS 3 BP 838 EP 841 DI 10.2337/diabetes.53.3.838 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 779NV UT WOS:000189307500040 PM 14988271 ER PT J AU Fox, CS Sullivan, L D'Agostino, RB Wilson, PWF AF Fox, CS Sullivan, L D'Agostino, RB Wilson, PWF TI The significant effect of diabetes duration on coronary heart disease morality - The Framingham Heart Study SO DIABETES CARE LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; CARDIOVASCULAR-DISEASE; RATE-VARIABILITY; BYPASS SURGERY; PIMA-INDIANS; MELLITUS; PREVALENCE; MORTALITY; IMPACT; RISK AB OBJECTIVE - The risk of coronary heart disease (CHD) in type 2 diabetes is two- to threefold higher than in the general population, but the effect of diabetes duration on CHD risk has not been well characterized. We hypothesized that duration of diabetes is an important predictor of incident CHD among people with diabetes. RESEARCH DESIGN AND METHODS- The duration of diabetes (fasting glucose 126 mg/dl, random glucose greater than or equal to200 mg/dl, or use of an oral hypoglycemic agent or insulin) was assessed in participants with diabetes in the original and offspring cohorts of the Framingham Heart Study. Only subjects with diabetes diagnosed between the ages of 30 and 74 years, without a history of ketoacidosis, and free of cardiovascular disease at the baseline evaluation were included. Cox proportional hazards models were used to estimate the hazard ratio of incident CHD events and mortality over a 12-year follow-up period; models were adjusted for known CHD risk factors. RESULTS- Among 588 person-exams with diabetes (mean age 58 +/- 9 years, 56% men), there were 86 CHD events, including 36 deaths. After adjustment for age, sex, and CHD risk factors, the risk of CHD was 1.38 times higher for each 10-year increase in duration of diabetes (95% CI 0.99-1.92), and the risk for CHD death was 1.86 times higher (1.17-2.93) for the same increase in duration of diabetes. CONCLUSIONS- Duration of diabetes increases the risk of CHD death independent of coexisting risk factors. Further research is necessary to understand the pathophysiology of this increased risk. C1 NHLBI, Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA. NHLBI, NIH, Framingham, MA 01702 USA. Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. Boston Univ, Sch Med, Boston, MA 02215 USA. RP Fox, CS (reprint author), NHLBI, Framingham Heart Dis Epidemiol Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM caroline@fram.nhlbi.nih.gov FU NHLBI NIH HHS [N01-HC-25195] NR 33 TC 110 Z9 115 U1 0 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD MAR PY 2004 VL 27 IS 3 BP 704 EP 708 DI 10.2337/diacare.27.3.704 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 779NU UT WOS:000189307400011 PM 14988289 ER PT J AU Rewers, M Zaccaro, D D'Agostino, R Haffner, S Saad, MF Selby, JV Bergman, R Savage, P AF Rewers, M Zaccaro, D D'Agostino, R Haffner, S Saad, MF Selby, JV Bergman, R Savage, P CA Insulin Resistance Atherosclerosis TI Insulin sensitivity, insulinemia, and coronary artery disease - The insulin resistance atherosclerosis study SO DIABETES CARE LA English DT Article ID DEPENDENT-DIABETES-MELLITUS; ISCHEMIC-HEART-DISEASE; MINIMAL MODEL ANALYSIS; BETA-CELL FUNCTION; GLUCOSE-TOLERANCE; PLASMA-INSULIN; RISK-FACTORS; HYPERINSULINEMIA; DYSLIPIDEMIA; NIDDM AB OBJECTIVE- The aim of this study was to evaluate whether low insulin sensitivity (S;) measured using a modified frequently sampled intravenous glucose tolerance test with minimal model analysis is associated with coronary artery disease (CAD) independent of other cardiovascular risk factors. RESEARCH DESIGN AND METHODS- We studied 1,482 women and men, age 40-69 years old, African American (28%), Hispanic (34%), or non-Hispanic white (38%), with normal (45%), impaired (23%), or diabetic (32%) glucose tolerance. CAD defined as confirmed past myocardial infarction, coronary artery bypass graft, coronary angioplasty, or presence of a major Q-wave was found in 91 participants. RESULTS- The odds ratio (OR) for CAD was greatest among individuals in the two lowest quintiles of S-i (2.4, 95% CI 1.0-5.6 and 4.7, 2.1-10.7) compared with the highest S-i quintile. After adjusting for demographic and cardiovascular risk factors, a decrement from the 75th to 25th percentile in S-i was associated with a 56% increase in CAD (P = 0.028). Similar increments in fasting or 2-h insulin levels were associated with, respectively, only 15 (NS) and 3% (NS) increases in CAD. The association between S-i and CAD was partially mediated by insulin, HDL cholesterol and triglyceride levels, hypertension, diabetes, and obesity, but not LDL cholesterol or cigarette smoking. CONCLUSIONS- Low S-i is associated with CAD independently of and stronger than plasma insulin levels. Part of the association is accounted for by dyslipidemia, hypertension, diabetes, and obesity. C1 Univ Colorado, Hlth Sci Ctr, Barbara Davis Ctr, Denver, CO 80262 USA. Wake Forest Univ, Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27109 USA. Univ Texas, Dept Med, San Antonio, TX 78285 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. Univ So Calif, Dept Physiol & Biophys, Los Angeles, CA USA. Kaiser Res Ctr, Div Res, Oakland, CA USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. RP Rewers, M (reprint author), Univ Colorado, Hlth Sci Ctr, Barbara Davis Ctr, B-140,4200 E 9th Ave, Denver, CO 80262 USA. EM marian.rewers@uchsc.edu RI Dagostino Jr, Ralph/C-4060-2017 OI Dagostino Jr, Ralph/0000-0002-3550-8395 FU NCRR NIH HHS [M01-RR-43]; NHLBI NIH HHS [HL-47889, HL-47890, HL-47892, HL-47902, U01-HL-47887] NR 41 TC 75 Z9 77 U1 1 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD MAR PY 2004 VL 27 IS 3 BP 781 EP 787 DI 10.2337/diacare.27.3.781 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 779NU UT WOS:000189307400024 PM 14988302 ER PT J AU Faucette, SR Wang, HB Hamilton, GA Jolley, SL Gilbert, D Lindley, C Yan, BF Negishi, M LeCluyse, EL AF Faucette, SR Wang, HB Hamilton, GA Jolley, SL Gilbert, D Lindley, C Yan, BF Negishi, M LeCluyse, EL TI Regulation of CYP2B6 in primary human hepatocytes by prototypical inducers SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID PREGNANE-X-RECEPTOR; HUMAN CYTOCHROME P4502B6; HUMAN LIVER-MICROSOMES; CONSTITUTIVE ANDROSTANE RECEPTOR; RESPONSIVE ENHANCER MODULE; NUCLEAR RECEPTOR; CATALYTIC-ACTIVITY; PRIMARY CULTURES; GENE-EXPRESSION; IFOSFAMIDE ACTIVATION AB The objectives of this study were to evaluate the ability of 14 compounds, which differentially activate human pregnane X receptor (hPXR), to induce CYP2B6 expression and to compare CYP2B6 and CYP3A4 concentration- and time-dependent induction by select inducers. Three primary human hepatocyte preparations were treated daily for 3 days with three concentrations of all compounds. Additional concentration- and/or time-response studies were conducted with clotrimazole, phenytoin, phenobarbital, and rifampin in six preparations. CYP2B6 and CYP3A4 protein and activities were assessed by Western blotting, bupropion hydroxylation, and testosterone 6beta-hydroxylation, respectively. To evaluate hPXR activation by the 14 compounds, reporter gene assays were conducted using Huh7 cells cotransfected with hPXR and a CYP2B6 (NR1)(5)-LUC reporter plasmid. Clotrimazole, phenobarbital, rifampin, and ritonavir strongly induced CYP2B6 and activated hPXR; dexamethasone t-butylacetate and sulfinpyrazone induced CYP2B6 weakly and activated hPXR moderately; paclitaxel strongly activated hPXR but did not increase CYP2B6 expression; carbamazepine and phenytoin moderately or strongly increased CYP2B6 expression but weakly activated hPXR; and dexamethasone, methotrexate, probenecid, sulfadimidine, and troleandomycin demonstrated weak or negligible effects on CYP2B6 and hPXR. EC50 values for CYP2B6 and CYP3A4 induction by clotrimazole, phenobarbital, phenytoin, and rifampin were strongly correlated (r(2) = 0.99) and were statistically indistinguishable for clotrimazole, phenytoin, and rifampin. Kinetic constants governing time-dependent induction by phenobarbital and rifampin were also similar between CYP2B6 and CYP3A4. These results indicate that CYP2B6 is highly inducible by known CYP3A4 inducers and suggest that hPXR is a major determinant of CYP2B6-inducible expression for many, but not all, compounds evaluated in this study. C1 Univ N Carolina, Sch Pharm, Div Drug Delivery & Disposit, Chapel Hill, NC 27599 USA. Univ N Carolina, Sch Pharm, Div Pharmacotherapy, Chapel Hill, NC 27599 USA. Univ Rhode Isl, Dept Biomed Sci, Kingston, RI 02881 USA. NIEHS, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP LeCluyse, EL (reprint author), Univ N Carolina, Sch Pharm, Div Drug Delivery & Disposit, CB 7360,Kerr Hall, Chapel Hill, NC 27599 USA. EM ed_lecluyse@unc.edu OI LeCluyse, Edward/0000-0002-2149-8990 FU NIDDK NIH HHS [DK061652] NR 49 TC 120 Z9 125 U1 0 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD MAR 1 PY 2004 VL 32 IS 3 BP 348 EP 358 DI 10.1124/dmd.32.3.348 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 776EW UT WOS:000189104600010 PM 14977870 ER PT J AU Hanya, G Matsubara, M Sugiura, H Hayakawa, S Goto, S Tanaka, T Soltis, J Noma, N AF Hanya, G Matsubara, M Sugiura, H Hayakawa, S Goto, S Tanaka, T Soltis, J Noma, N TI Mass mortality of Japanese macaques in a western coastal forest of Yakushima SO ECOLOGICAL RESEARCH LA English DT Article DE disease; intertroop competition; Japanese macaque; mass mortality; Yakushima ID MACACA-FUSCATA-YAKUI; TROOP EXTINCTION; 2 POPULATIONS; SIKA-DEER; ISLAND; BABOONS; CONSERVATION; COMPETITION; STRATEGIES; ECOLOGY AB The mass mortality of wild Japanese macaques (Macaca fuscata Blyth) was observed in a warm temperate forest of Yakushima, southern Japan. Demographic changes of eight troops between August 1998 and August 1999 were studied and 56% of macaques disappeared from the five intensively studied troops. Mortality varied among troops: two troops became extinct, while another troop did not decrease in size. The rate of mortality of the other troops was between 33 and 80%. The variation in mortality among the troops was either the outcome of local concentrations of mortality or of intertroop competition. The rate of mortality decreased with increasing distance from the two extinct troops and with increasing troop size; these two factors could not be separated statistically. The direct cause of death was diagnosed as pneumonia for four out of five fresh carcasses. The fleshy fruit production in autumn 1998 was the lowest in 14 years, and macaques had relied on leaves earlier than in usual years. It was exceptionally hot and dry in the summer of 1998. The exceptionally poor fruit production and hot summer of this year, with the resulting shortage of high-quality foods, was consistent with the scenario that mass mortality was due to the poor nutritional conditions. However, the possibility that epidemics caused the mass mortality cannot be ruled out. Our findings proved that primates in a seemingly stable habitat experience fluctuations in demographic parameters under natural conditions. C1 Kyoto Univ, Primate Res Inst, Inuyama, Aichi 4848506, Japan. Kyoto Univ, Grad Sch Sci, Dept Zool, Kyoto 6068502, Japan. Nihon Univ, Inst Humanities & Social Sci, Tokyo 1568550, Japan. NIH, Poolesville, MD 20837 USA. Univ Shiga Prefecture, Shiga, 5228533, Japan. RP Hanya, G (reprint author), Kyoto Univ, Primate Res Inst, Inuyama, Aichi 4848506, Japan. EM hanya@pri.kyoto-u.ac.jp RI Matsubara, Miki/G-1491-2011 NR 43 TC 10 Z9 10 U1 2 U2 17 PU BLACKWELL PUBLISHING ASIA PI CARLTON PA 54 UNIVERSITY ST, P O BOX 378, CARLTON, VICTORIA 3053, AUSTRALIA SN 0912-3814 J9 ECOL RES JI Ecol. Res. PD MAR PY 2004 VL 19 IS 2 BP 179 EP 188 DI 10.1111/j.1440-1703.2003.00622.x PG 10 WC Ecology SC Environmental Sciences & Ecology GA 802PV UT WOS:000220176300005 ER PT J AU Lyon, GR Chhabra, V AF Lyon, GR Chhabra, V TI The science of reading research SO EDUCATIONAL LEADERSHIP LA English DT Article ID DIFFICULTIES AB To prevent reading failure, educators must understand and act on scientific evidence. C1 Natl Inst Child Hlth & Human Dev, Child Dev & Behav Branch, Rockville, MD USA. RP Lyon, GR (reprint author), Natl Inst Child Hlth & Human Dev, Child Dev & Behav Branch, Rockville, MD USA. EM lyonr@mail.nih.gov; chhabrav@mail.nih.gov NR 27 TC 8 Z9 8 U1 2 U2 3 PU ASSOC SUPERVISION CURRICULUM DEVELOPMENT PI ALEXANDRIA PA 1703 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0013-1784 J9 EDUC LEADERSHIP JI Educ. Leadership PD MAR PY 2004 VL 61 IS 6 BP 12 EP 17 PG 6 WC Education & Educational Research SC Education & Educational Research GA 801EX UT WOS:000220080300003 ER PT J AU Rodriguez, CI Cheng, JG Liu, L Stewart, CL AF Rodriguez, CI Cheng, JG Liu, L Stewart, CL TI Cochlin, a secreted von Willebrand factor type a domain-containing factor, is regulated by leukemia inhibitory factor in the uterus at the time of embryo implantation SO ENDOCRINOLOGY LA English DT Article ID SENSORINEURAL HEARING-LOSS; EXTRACELLULAR-MATRIX; SUBTRACTIVE HYBRIDIZATION; BLASTOCYST IMPLANTATION; MOUSE MODEL; CAUSE DFNA9; GENE; DEAFNESS; MUTATION; COMMON AB Embryo implantation is a required step in the reproduction of all mammals. In mice, a transient rise in the uterine expression of leukemia inhibitory factor (LIF) occurs on d 4 of pregnancy and is essential for embryo implantation. However, which genes are regulated by LIF in the uterus at implantation has not been determined. We performed a subtractive hybridization assay between luminal epithelial (LE) mRNAs from d 3 and 4 of pregnancy to find genes up-regulated on d 4 and which would be potentially regulated by LIF. One candidate, Coch-5b2, was up-regulated on the day of implantation. Coch mRNA localized to the LE of wild-type mice and was not detected in uteri from Lif-deficient mice. Treatment of LE with LIF, both in vitro and in vivo, resulted in the up-regulation of Coch. Coch is also highly expressed in other tissues, including the spleen and inner ear, but only in the uterus is Coch expression regulated by LIF. Mice were derived in which Coch was either deleted or tagged with a LacZ reporter. In mice carrying the tagged Coch gene, expression of Coch was detected in the LE and also at the site of embryo implantation. However, mice in which the Coch gene was deleted were normal, showing no overt defects in their reproduction. Although loss of Coch expression is not essential to reproduction in mice, it may serve as a useful marker for assessing the state of uterine receptivity in response to LIF at the onset of implantation. C1 NCI, Canc & Dev Biol Lab, Div Basic Sci, Frederick, MD 21702 USA. RP Stewart, CL (reprint author), NCI, Canc & Dev Biol Lab, Div Basic Sci, Bldg 539,Room 121, Frederick, MD 21702 USA. EM stewartc@ncifcrf.gov RI Rodriguez, Clara/E-4835-2012; Rodriguez, Clara/E-5402-2012 NR 49 TC 31 Z9 33 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD MAR 1 PY 2004 VL 145 IS 3 BP 1410 EP 1418 DI 10.1210/en.2003-1361 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 775HW UT WOS:000189035500052 PM 14657014 ER PT J AU Tong, ZB Gold, L De Pol, A Vanevski, K Dorward, H Sena, P Palumbo, C Bondy, CA Nelson, LM AF Tong, ZB Gold, L De Pol, A Vanevski, K Dorward, H Sena, P Palumbo, C Bondy, CA Nelson, LM TI Developmental expression and subcellular localization of mouse MATER, an oocyte-specific protein essential for early development SO ENDOCRINOLOGY LA English DT Article ID PREIMPLANTATION EMBRYO DEVELOPMENT; ZONA-PELLUCIDA; GENE-EXPRESSION; MESSENGER-RNA; MITOCHONDRIA; TRANSITION; UNMASKING; DIVERSITY; PATTERN; OVARIAN AB We reported previously that Mater is a maternal effect gene that is required for early embryonic development beyond the two-cell stage in mice. Here we show the expressional profile of Mater and its protein during oogenesis and embryogenesis as well as its subcellular localization in oocytes. Mater mRNA was detectable earliest in oocytes of type 2 follicles, whereas MATER protein appeared earliest in oocytes of type 3a primary follicles. Both mRNA and protein accumulated during oocyte growth. In situ hybridization showed that Mater mRNA appeared progressively less abundant in oocytes beyond type 5a primary follicles. By ribonuclease protection assay, Mater mRNA was abundant in germinal vesicle oocytes, but was undetectable in all stages of preimplantation embryos. In contrast, the protein persisted throughout preimplantation development. Immunogold electron microscopic analysis revealed that MATER was located in oocyte mitochondria and nucleoli, and close to nuclear pores. Taken together, our data indicate that Mater gene transcription and protein translation are active during oogenesis, but appear inactive during early embryogenesis. Thus, Mater and its protein are expressed in a manner typical of maternal effect genes. The presence of MATER protein in mitochondria and nucleoli suggests that it may participate in both cytoplasmic and nuclear events during early development. C1 NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NIDDKD, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. Univ Modena & Riggio Emilia, Fac Med & Chirurg, Dept Anat & Histol, I-41100 Modena, Italy. RP Tong, ZB (reprint author), NICHHD, Dev Endocrinol Branch, NIH, Bldg 10Room 10N262, Bethesda, MD 20892 USA. EM tongz@exchange.nih.gov RI Palumbo, Carla/E-5802-2012; Sena, Paola/G-9394-2016; OI Palumbo, Carla/0000-0003-0587-0112; Sena, Paola/0000-0003-4724-8786; DE POL, Anto/0000-0003-4279-5422 NR 37 TC 64 Z9 68 U1 0 U2 4 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD MAR 1 PY 2004 VL 145 IS 3 BP 1427 EP 1434 DI 10.1210/en.2003-031160 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 775HW UT WOS:000189035500054 PM 14670992 ER PT J AU Jahnke, GD Choksi, NY Moore, JA Shelby, MD AF Jahnke, GD Choksi, NY Moore, JA Shelby, MD TI Thyroid toxicants: Assessing reproductive health effects SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE chemical screening; chemical testing; developmental; perinatal exposure; reproductive; thyroid gland; thyroid hormones; toxicology ID SERTOLI-CELLS; HORMONE; DISEASE; SYSTEM; MODEL; MICE; RAT AB A thyroid toxicant workshop sponsored by the National Toxicology Program Center for the Evaluation of Risks to Human Reproduction convened on 28-29 April 2003 in Alexandria, Virginia. The purpose of this workshop was to examine and discuss chemical-induced thyroid dysfunction in experimental animals and the relevance of reproductive and developmental effects observed for prediction of adverse effects in humans. Presentations highlighted and compared reproductive and developmental effects of thyroid hormones in humans and rodents. Rodent models of thyroid system dysfunction were presented. Animal testing protocols were reviewed, taking into account protocol designs that allow extrapolation to possible human health effects. Potential screening methods to assess toxicant-induced thyroid dysfunction were outlined, and postnatal bioassays of thyroid-related effects were discussed. C1 US Dept HHS, NIEHS, NIH, NTP,CERHR, Res Triangle Pk, NC 27709 USA. Sci Int Inc, Res Triangle Pk, NC USA. Sci Int Inc, Alexandria, VA USA. RP Jahnke, GD (reprint author), US Dept HHS, NIEHS, NIH, NTP,CERHR, POB 12233,MD EC-32, Res Triangle Pk, NC 27709 USA. EM jahnke@niehs.nih.gov FU NIEHS NIH HHS [N01 ES 85425] NR 29 TC 45 Z9 47 U1 1 U2 4 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD MAR PY 2004 VL 112 IS 3 BP 363 EP 368 DI 10.1289/ehp.6637 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 800SJ UT WOS:000220047700037 PM 14998754 ER PT J AU Quandt, SA Arcury, TA Rao, P Snively, BM Camann, DE Doran, AM Yau, AY Hoppin, JA Jackson, DS AF Quandt, SA Arcury, TA Rao, P Snively, BM Camann, DE Doran, AM Yau, AY Hoppin, JA Jackson, DS TI Agricultural and residential pesticides in wipe samples from farmworker family residences in North Carolina and Virginia SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE agriculture; children; exposure; house dust; Latino ID EXPOSURE ASSESSMENT; CHILDREN; COMMUNITY; WORKERS; CHLORPYRIFOS; ENVIRONMENT; PREGNANCY; PATHWAYS; COHORT AB Children of farmworkers can be exposed to pesticides through multiple pathways, including agricultural take-home and drift as well as residential applications. Because farmworker families often live in poor-quality housing, the exposure from residential pesticide use may be substantial. We measured eight locally reported agricultural pesticides and 13 pesticides commonly found in U.S. houses in residences of 41 farmworker families with at least one child < 7 years of age in western North Carolina and Virginia. Wipe samples were taken from floor surfaces, toys, and children's hands. We also collected interview data on possible predictors of pesticide presence, including characteristics of the household residents, cleaning practices, and characteristics of the home. All families were Spanish-speaking, primarily from Mexico. Results indicate that six agricultural and 11 residential pesticides were found in the homes, with agricultural, residential, or both present in 95% of homes sampled. In general, residential pesticides were more commonly found. Presence of both types of pesticides on the floor was positively associated with detection on toys or hands. Agricultural pesticide detection was associated with housing adjacent to agricultural fields. Residential pesticide detection was associated with houses judged difficult to clean. Although the likelihood of agricultural pesticide exposure has been considered high for farmworker families, these results indicate that residential pesticide use and exposure in this population merit further study. C1 Wake Forest Univ, Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27157 USA. Wake Forest Univ, Sch Med, Dept Family & Community Med, Winston Salem, NC 27157 USA. SW Res Inst, San Antonio, TX USA. NIEHS, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Quandt, SA (reprint author), Wake Forest Univ, Sch Med, Dept Publ Hlth Sci, Med Ctr Blvd,Piedmont Pl 2,Suite 512, Winston Salem, NC 27157 USA. EM squandt@wfubmc.edu NR 29 TC 82 Z9 87 U1 2 U2 15 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD MAR PY 2004 VL 112 IS 3 BP 382 EP 387 DI 10.1289/ehp.6554 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 800SJ UT WOS:000220047700040 PM 14998757 ER PT J AU Toraason, M Albertini, R Bayard, S Bigbee, W Blair, A Boffetta, P Bonassi, S Chanock, S Christiani, D Eastmond, D Hanash, S Henry, C Kadlubar, F Mirer, F Nebert, D Rapport, S Rest, K Rothman, N Ruder, A Savage, R Schulte, P Siemiatycki, J Shields, P Smith, M Tolbert, P Vermeulen, R Vineis, P Wacholder, S Ward, E Waters, M Weston, A AF Toraason, M Albertini, R Bayard, S Bigbee, W Blair, A Boffetta, P Bonassi, S Chanock, S Christiani, D Eastmond, D Hanash, S Henry, C Kadlubar, F Mirer, F Nebert, D Rapport, S Rest, K Rothman, N Ruder, A Savage, R Schulte, P Siemiatycki, J Shields, P Smith, M Tolbert, P Vermeulen, R Vineis, P Wacholder, S Ward, E Waters, M Weston, A TI Applying new biotechnologies to the study of occupational cancer - A workshop summary SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE biomarkers; chemical exposure; epidemiology; gene-environment interactions; genomics; occupational cancer; polymorphisms; proteomics; risk assessment; toxicogenomics AB As high-throughput technologies in genomics, transcriptomics, and proteomics evolve, questions arise about their use in the assessment of occupational cancers. To address these questions, the National Institute for Occupational Safety and Health, the National Cancer Institute, the National Institute of Environmental Health Sciences, and the American Chemistry Council sponsored a workshop 8-9 May 2002 in Washington, DC. The workshop brought together 80 international specialists whose objective was to identify the means for best exploiting new technologies to enhance methods for laboratory investigation, epidemiologic evaluation, risk assessment, and prevention of occupational cancer. The workshop focused on identifying and interpreting markers for early biologic effect and inherited modifiers of risk. C1 NIOSH, Cincinnati, OH 45226 USA. Univ Vermont, Burlington, VT USA. Occupat Safety & Hlth Adm, Washington, DC USA. Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. NCI, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. Int Agcy Res Canc, F-69372 Lyon, France. Natl Inst Canc Res, Genoa, Italy. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Univ Calif Riverside, Riverside, CA 92521 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Amer Chem Council, Arlington, VA USA. Natl Ctr Toxicol Res, Jefferson, AR USA. United Auto Workers Union, Int Union, Hlth & Safety Dept, Detroit, MI USA. Univ Cincinnati, Cincinnati, OH USA. Univ N Carolina, Chapel Hill, NC USA. NIOSH, Washington, DC USA. Univ Montreal, Montreal, PQ, Canada. Georgetown Univ, Washington, DC USA. Univ Calif Berkeley, Berkeley, CA 94720 USA. Emory Univ, Atlanta, GA 30322 USA. Univ Turin, Turin, Italy. Amer Canc Soc, Atlanta, GA 30329 USA. NIEHS, Dept Hlth & Human Serv, NIH, Res Triangle Pk, NC 27709 USA. NIOSH, Morgantown, WV 26505 USA. RP Toraason, M (reprint author), NIOSH, C23,4676 Columbia Pkwy, Cincinnati, OH 45226 USA. EM mtoraason@cdc.gov RI Waters, Martha/B-7441-2011; Shields, Peter/I-1644-2012; Ruder, Avima/I-4155-2012; Tolbert, Paige/A-5676-2015; Vermeulen, Roel/F-8037-2011; OI Ruder, Avima/0000-0003-0419-6664; Vermeulen, Roel/0000-0003-4082-8163; bonassi, stefano/0000-0003-3833-6717 NR 5 TC 21 Z9 23 U1 0 U2 3 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD MAR PY 2004 VL 112 IS 4 BP 413 EP 416 DI 10.1289/txg.6343 PG 4 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 807BS UT WOS:000220477600012 PM 15033588 ER PT J AU Chu, TM Deng, SB Wolfinger, R Paules, RS Hamadeh, HK AF Chu, TM Deng, SB Wolfinger, R Paules, RS Hamadeh, HK TI Cross-site comparison of gene expression data reveals high similarity SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE cross-site comparison; gene expression; hepatotoxicity; ILSI; toxicogenomics ID OLIGONUCLEOTIDE ARRAYS; NORMALIZATION AB Consistency and coherence of gene expression data across multiple sites depends on several factors such as platform (oligo, cDNA, etc.), environmental conditions at each laboratory, and data quality. The Hepatotoxicity Working Group of the International Life Sciences Institute Health and Environmental Sciences Institute consortium on the application of genomics to mechanism-based risk assessment is investigating these factors by comparing high-density gene expression data sets generated on two sets of RNA from methapyrilene (MP) experiments conducted at Abbott Laboratories and Boehringer-Ingelheim Pharmaceuticals, Inc. using a single platform (Affymetrix Rat Genome U34A GeneChip) at seven different sites. This article focuses on the evaluation of data quality and statistical models that facilitate the comparison of such data sets at the probe level. We present methods for exploring and quantitatively assessing differences in the data, with the principal goal being the generation of lists of site-insensitive genes responsive to low and high doses of MP. A combination of numerical and graphical techniques reveals important patterns and partitions of variability in the data, including the magnitude of the site effects. Although the site effects are significantly large in the analysis results, they appear to be primarily additive and therefore can be adjusted in the statistical calculations in a way that does not bias conclusions regarding treatment differences. C1 Amgen Inc, Newbury Pk, CA 91320 USA. SAS Inst Inc, Cary, NC USA. NIEHS, Dept Hlth & Human Serv, NIH, Res Triangle Pk, NC 27709 USA. RP Hamadeh, HK (reprint author), Amgen Inc, 1 Amgen Ctr Dr,Mail Drop 5-1-A, Newbury Pk, CA 91320 USA. EM hhamadeh@amgen.com NR 13 TC 36 Z9 41 U1 0 U2 1 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD MAR PY 2004 VL 112 IS 4 BP 449 EP 455 DI 10.1289/txg.6787 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 807BS UT WOS:000220477600018 PM 15033594 ER PT J AU Kramer, JA Pettit, SD Amin, RP Bertram, TA Car, B Cunningham, M Curtiss, SW Davis, JW Kind, C Lawton, M Naciff, JM Oreffo, V Roman, RJ Sistare, FD Stevens, J Thompson, K Vickers, AE Wild, S Afsharif, CA AF Kramer, JA Pettit, SD Amin, RP Bertram, TA Car, B Cunningham, M Curtiss, SW Davis, JW Kind, C Lawton, M Naciff, JM Oreffo, V Roman, RJ Sistare, FD Stevens, J Thompson, K Vickers, AE Wild, S Afsharif, CA TI Overview of the application of transcription profiling using selected nephrotoxicants for toxicology assessment SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE cisplatin; gentamicin; nephrotoxicity; puromycin; risk assessment ID GENTAMICIN AB Microarrays allow for the simultaneous measurement of changes in the levels of thousands of messenger RNAs within a single experiment. As such, the potential for the application of transcription profiling to preclinical safety assessment and mechanism-based risk assessment is profound. However, several practical and technical challenges remain. Among these are nomenclature issues, platform-specific data formats, and the lack of uniform analysis methods and tools. Experiments were designed to address biological, technical, and methodological variability, to evaluate different approaches to data analysis, and to understand the application of the technology to other profiling methodologies and to mechanism-based risk assessment. These goals were addressed using experimental information derived from analysis of the biological response to three mechanistically distinct nephrotoxins: cisplatin, gentamicin, and puromycin aminonucleoside. In spite of the technical challenges, the transcription profiling data yielded mechanistically and topographically valuable information. The analyses detailed in the articles from the Nephrotoxicity Working Group of the International Life Sciences Institute Health and Environmental Sciences Institute suggest at least equal sensitivity of microarray technology compared to traditional end points. Additionally, microarray analysis of these prototypical nephrotoxicants provided an opportunity for the development of candidate bridging biomarkers of nephrotoxicity. The potential future extension of these applications for risk assessment is also discussed. C1 ILSI Hlth & Environm Sci Inst, Washington, DC 20005 USA. Pfizer Inc, St Louis, MO USA. Pfizer Inc, Groton, CT 06340 USA. NIEHS, Dept Hlth & Human Serv, NIH, Res Triangle Pk, NC USA. Bristol Myers Squibb Co, Wilmington, DE USA. Schering Plough Res Inst, Lafayette, NJ USA. AstraZeneca, Charnwood, Leics, England. Procter & Gamble Co, Miami Valley Labs, Cincinnati, OH USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. US FDA, Ctr Drug Evaluat & Res, Laurel, MD USA. Eli Lilly & Co, Greenfield, IN 46140 USA. Novartis Pharmaceut Corp, E Hanover, NJ USA. Amgen Inc, Thousand Oaks, CA 91320 USA. RP Pettit, SD (reprint author), ILSI Hlth & Environm Sci Inst, 1 Thomas Circle NW,9th Floor, Washington, DC 20005 USA. EM spettit@ilsi.org NR 16 TC 39 Z9 47 U1 1 U2 3 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD MAR PY 2004 VL 112 IS 4 BP 460 EP 464 DI 10.1289/txg.6673 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 807BS UT WOS:000220477600020 PM 15033596 ER PT J AU Amin, RA Vickers, AE Sistare, F Thompson, KL Roman, RJ Lawton, M Kramer, J Hamadeh, HK Collins, J Grissom, S Bennett, L Tucker, CJ Wild, S Kind, C Oreffo, V Davis, JW Curtiss, S Naciff, JM Cunningham, M Tennant, R Stevens, J Car, B Bertram, TA Afsharil, CA AF Amin, RA Vickers, AE Sistare, F Thompson, KL Roman, RJ Lawton, M Kramer, J Hamadeh, HK Collins, J Grissom, S Bennett, L Tucker, CJ Wild, S Kind, C Oreffo, V Davis, JW Curtiss, S Naciff, JM Cunningham, M Tennant, R Stevens, J Car, B Bertram, TA Afsharil, CA TI Identification of putative gene-based markers of renal toxicity SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE biomarkers; cisplatin; gentamicin; microarrays; nephrotoxicity; proximal tubule; puromycin; toxicogenomics ID PROSTAGLANDIN-D SYNTHASE; KIDNEY INJURY MOLECULE-1; LIPOCALIN PROTEIN FAMILY; RETINOL-BINDING PROTEIN; BETA-TRACE PROTEIN; MESSENGER-RNA; OSTEOPONTIN EXPRESSION; INDUCED NEPHROTOXICITY; MICROARRAY ANALYSIS; EPITHELIAL-CELLS AB This study, designed and conducted as part of the International Life Sciences Institute working group on the Application of Genomics and Proteomics, examined the changes in the expression profile of genes associated with the administration of three different nephrotoxicants-cisplatin, gentamicin, and puromycin-to assess the usefulness of microarrays in the understanding of mechanism(s) of nephrotoxicity. Male Sprague-Dawley rats were treated with daily doses of puromycin (5-20 mg/kg/day for 21 days), gentamicin (2-240 mg/kg/day for 7 days), or a single dose of cisplatin (0.1-5 mg/kg). Groups of rats were sacrificed at various times after administration of these compounds for standard clinical chemistry, urine analysis, and histological evaluation of the kidney. RNA was extracted from the kidney for microarray analysis. Principal component analysis and gene expression-based clustering of compound effects confirmed sample separation based on dose, time, and degree of renal toxicity. In addition, analysis of the profile components revealed some novel changes in the expression of genes that appeared to be associated with injury in specific portions of the nephron and reflected the mechanism of action of these various nephrotoxicants. For example, although puromycin is thought to specifically promote injury of the podocytes in the glomerulus, the changes in gene expression after chronic exposure of this compound suggested a pattern similar to the known proximal tubular nephrotoxicants cisplatin and gentamicin; this prediction was confirmed histologically. We conclude that renal gene expression profiling coupled with analysis of classical end points affords promising opportunities to reveal potential new mechanistic markers of renal toxicity. C1 NIEHS, Dept Hlth & Human Serv, NIH, Res Triangle Pk, NC 27709 USA. Novartis Pharmaceut Corp, E Hanover, NJ USA. US FDA, Ctr Drug Evaluat & Res, Laurel, MD USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. Physiogenix Inc, Milwaukee, WI USA. Pfizer Inc, St Louis, MO USA. Pfizer Inc, Groton, CT 06340 USA. Amgen Inc, Thousand Oaks, CA 91320 USA. Schering Plough Res Inst, Lafayette, NJ USA. Procter & Gamble Co, Miami Valley Labs, Cincinnati, OH USA. Eli Lilly & Co, Indianapolis, IN 46285 USA. Bristol Myers Squibb Co, Wilmington, DE USA. RP Afsharil, CA (reprint author), NIEHS, Dept Hlth & Human Serv, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM cafshari@amgen.com NR 80 TC 155 Z9 174 U1 1 U2 6 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD MAR PY 2004 VL 112 IS 4 BP 465 EP 479 DI 10.1289/txg.6683 PG 15 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 807BS UT WOS:000220477600021 PM 15033597 ER PT J AU Thompson, KL Afshari, CA Amin, RA Bertram, TA Car, B Cunningham, M Kind, C Kramer, JA Lawton, M Mirsky, M Naciff, JM Oreffo, V Pine, PS Sistare, FD AF Thompson, KL Afshari, CA Amin, RA Bertram, TA Car, B Cunningham, M Kind, C Kramer, JA Lawton, M Mirsky, M Naciff, JM Oreffo, V Pine, PS Sistare, FD TI Identification of platform-independent gene expression markers of cisplatin nephrotoxicity SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE cisplatin; cross-platform; kidney; microarrays; nephrotoxicity ID GLOBAL ANALYSIS; PROFILES AB Within the International Life Sciences Institute Committee on Genomics, a working group was formed to focus on the application of microarray technology to preclinical assessments of drug-induced nephrotoxicity. As part of this effort, Sprague-Dawley rats were treated with the nephrotoxicant cisplatin at doses of 0.3-5 mg/kg over a 4- to 144-hr time course. RNA prepared from these animals was run on a variety of microarray formats at multiple sites. A set of 93 differentially expressed genes associated with cisplatin-induced renal injury was identified on the National Institute of Environmental Health Sciences (NIEHS) custom cDNA microarray platform using quadruplicate measurements of pooled animal RNA. The reproducibility of this profile of statistically significant gene changes on other platforms, in pooled and individual animal replicate samples, and in an independent study was investigated. A good correlation in response between platforms was found among the 48 genes in the NIEHS data set that could be matched to probes on the Affymetrix RGU34A array by UniGene identifier or sequence alignment. Similar results were obtained with genes that could be linked between the NIEHS and Incyte or PHASE-1 arrays. The degree of renal damage induced by cisplatin in individual animals was commensurate with the number of differentially expressed genes in this data set. These results suggest that gene profiles linked to specific types of tissue injury or mechanisms of toxicity and identified in well-performed replicated microarray experiments may be extrapolatable across platform technologies, laboratories, and in-life studies. C1 US FDA, CDER, Div Appl Pharmacol Res, Silver Spring, MD 20993 USA. Amgen Inc, Thousand Oaks, CA 91320 USA. NIEHS, Dept Hlth & Human Serv, NIH, Res Triangle Pk, NC 27709 USA. Pfizer Inc, St Louis, MO USA. Pfizer Inc, Groton, CT 06340 USA. Bristol Myers Squibb Co, Wilmington, DE USA. AstraZeneca Res & Dev, Charnwood, Leics, England. Procter & Gamble Co, Cincinnati, OH USA. RP Thompson, KL (reprint author), US FDA, CDER, Div Appl Pharmacol Res, HFD-910,Life Sci Bldg 64,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Thompsonk@cder.fda.gov NR 19 TC 54 Z9 59 U1 0 U2 2 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD MAR PY 2004 VL 112 IS 4 BP 488 EP 494 DI 10.1289/txg.6676 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 807BS UT WOS:000220477600023 PM 15033599 ER PT J AU Mattes, WB Pettit, SD Sansone, SA Bushel, PR Waters, MD AF Mattes, WB Pettit, SD Sansone, SA Bushel, PR Waters, MD TI Database development in toxicogenomics: Issues and efforts SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE ArrayExpress; bioinformatics; CEBS; database; EBI; HESI; MIAME; NCT; toxicogenomics ID GENE-EXPRESSION; MICROARRAY DATA; DATA-MANAGEMENT; HYBRIDIZATION; TECHNOLOGIES; INFORMATION; TOXICOLOGY; REPOSITORY; STANDARDS; PATTERNS AB The marriage of toxicology and genomics has created not only opportunities but also novel informatics challenges. As with the larger field of gene expression analysis, toxicogenomics faces the problems of probe annotation and data comparison across different array platforms. Toxicogenomics studies are generally built on standard toxicology studies generating biological end point data, and as such, one goal of toxicogenomics is to detect relationships between changes in gene expression and in those biological parameters. These challenges are best addressed through data collection into a well-designed toxicogenomics database. A successful publicly accessible toxicogenomics database will serve as a repository for data sharing and as a resource for analysis, data mining, and discussion. It will offer a vehicle for harmonizing nomenclature and analytical approaches and serve as a reference for regulatory organizations to evaluate toxicogenomics data submitted as part of registrations. Such a database would capture the experimental context of in vivo studies with great fidelity such that the dynamics of the dose response could be probed statistically with confidence. This review presents the collaborative efforts between the European Molecular Biology Laboratory-European Bioinformatics Institute ArrayExpress, the International Life Sciences Institute Health and Environmental Science Institute, and the National Institute of Environmental Health Sciences National Center for Toxigenomics Chemical Effects in Biological Systems knowledge base. The goal of this collaboration is to establish public infrastructure on an international scale and examine other developments aimed at establishing toxicogenomics databases. In this review we discuss several issues common to such databases: the requirement for identifying minimal descriptors to represent the experiment, the demand for standardizing data storage and exchange formats, the challenge of creating standardized nomenclature and ontologies to describe biological data, the technical problems involved in data upload, the necessity of defining parameters that assess and record data quality, and the development of standardized analytical approaches. C1 Pfizer Inc, Groton, CT 06340 USA. ILSI Hlth & Environm Sci Inst, Washington, DC USA. European Mol Biol Lab, European Bioinformat Inst, Hinxton, England. NIEHS, Natl Ctr Toxicogenom, Dept Hlth & Human Serv, NIH, Res Triangle Pk, NC 27709 USA. RP Mattes, WB (reprint author), GeneLog Inc, 610 Profess Dr, Gaithersburg, MD 20879 USA. EM wmattes@genelogic.com OI Sansone, Susanna-Assunta/0000-0001-5306-5690 NR 38 TC 80 Z9 89 U1 1 U2 11 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD MAR PY 2004 VL 112 IS 4 BP 495 EP 505 DI 10.1289/txg.6697 PG 11 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 807BS UT WOS:000220477600024 PM 15033600 ER PT J AU Goehl, TJ Burkhart, JG AF Goehl, TJ Burkhart, JG TI Note from the editors: Online submission begins this month SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material C1 US Dept HHS, NIEHS, NIH, Res Triangle Pk, NC USA. RP Goehl, TJ (reprint author), US Dept HHS, NIEHS, NIH, Res Triangle Pk, NC USA. EM goehl@niehs.nih.gov; burkhart@niehs.nih.gov NR 0 TC 1 Z9 1 U1 0 U2 0 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD MAR PY 2004 VL 112 IS 3 BP A146 EP A146 PG 1 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 800SJ UT WOS:000220047700003 ER PT J AU Olden, K AF Olden, K TI Relevance of the National Institutes of Health Roadmap initiatives to the field of environmental health SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material C1 US Dept HHS, NIEHS, NIH, Res Triangle Pk, NC USA. RP Olden, K (reprint author), US Dept HHS, NIEHS, NIH, Res Triangle Pk, NC USA. EM olden@niehs.nih.gov NR 0 TC 0 Z9 1 U1 0 U2 0 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD MAR PY 2004 VL 112 IS 3 BP A145 EP A146 PG 2 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 800SJ UT WOS:000220047700002 PM 15049301 ER PT J AU Zhang, J Christianson, RE Torfs, CP AF Zhang, J Christianson, RE Torfs, CP TI Fetal trisomy 21 and maternal preeclampsia SO EPIDEMIOLOGY LA English DT Article ID SYNCYTIOTROPHOBLAST MICROVILLOUS MEMBRANES; HUMAN CHORIONIC-GONADOTROPIN; DOWNS-SYNDROME; DNA CONCENTRATIONS; OXIDATIVE STRESS; PREGNANT-WOMEN; UNITED-STATES; SERUM INHIBIN; ACTIVIN-A; PLASMA AB Background: Placental trophoblast shedding into maternal circulation has been hypothesized as a potential cause of preeclampsia. Because pregnancies with a trisomy 21 fetus also have high levels of fetal cells and cell-free fetal DNA in maternal circulation, we examined whether trisomy 21 pregnancies have a higher risk of preeclampsia than euploid pregnancies. Methods: We used 2 population-based databases. We identified 7763 pregnancies with a singleton trisomy 21-affected fetus and 15,293 matched euploid gestations from the U.S. Natality files for the period 1995-1999. The second database consisted of 665 pregnancies with fetal trisomy 21 and 987 euploid controls in a population-based Down syndrome study in California. In the latter study, women were interviewed by telephone regarding characteristics and pregnancy complications. Gestational hypertension and preeclampsia are the outcomes of this study. Results: The U.S. Natality files showed that in nulliparous women fetal trisomy 21 was associated with a reduced risk of pregnancy-induced hypertension (adjusted relative risk [aRR] = 0.67; 95% confidence interval [CI] = 0.53 to 0.85). Findings from the California study confirmed this association in nulliparous women, and further revealed that the decrease in overall risk of pregnancy-induced hypertension was mainly the result of a large reduction in the risk of preeclampsia (aRR = 0.19; CI = 0.04 to 0.88) rather than in gestational hypertension by itself (0.83; 0.37 to 1.84). Neither dataset showed these effects among multiparous pregnancies. Conclusion: Fetal trisomy 21 is associated with a reduced, rather than increased, risk of preeclampsia, specifically in nulliparous women. C1 NICHHD, Epidemiol Branch, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. Inst Publ Hlth, Berkeley, CA USA. RP Zhang, J (reprint author), NICHHD, Epidemiol Branch, Dept Hlth & Human Serv, NIH, Bldg 6100,Room 7B03, Bethesda, MD 20892 USA. EM jim_zhang@nih.gov NR 28 TC 7 Z9 7 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD MAR PY 2004 VL 15 IS 2 BP 195 EP 201 DI 10.1097/01.ede.0000112141.09008.37 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 779GL UT WOS:000189286900012 PM 15127912 ER PT J AU Weinberg, C AF Weinberg, C TI Arsenic and drinking water SO EPIDEMIOLOGY LA English DT Letter C1 NIEHS, Res Triangle Pk, NC 27709 USA. RP Weinberg, C (reprint author), NIEHS, Mail Drop A3-03,Box 12233, Res Triangle Pk, NC 27709 USA. EM weinberg@niehs.nih.gov NR 2 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD MAR PY 2004 VL 15 IS 2 BP 255 EP 255 DI 10.1097/01.ede.0000112147.22515.f7 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 779GL UT WOS:000189286900024 PM 15127923 ER PT J AU Theodore, WH Kelley, K Toczek, MT Gaillard, WD AF Theodore, WH Kelley, K Toczek, MT Gaillard, WD TI Epilepsy duration, febrile seizures, and cerebral glucose metabolism SO EPILEPSIA LA English DT Article DE epilepsy duration; febrile seizures; cerebral glucose metabolism ID TEMPORAL-LOBE EPILEPSY; HIPPOCAMPAL ATROPHY; BLOOD-FLOW; FDG-PET; HYPOMETABOLISM; CHILDREN; BINDING; ONSET; LONG; MRI AB Purpose: Studies using magnetic resonance imaging have shown that reduced hippocampal volume is associated with a history of febrile seizures, the duration of epilepsy. and the number of generalized tonic-clonic seizures. It is uncertain whether these factors have the same influence on functional as on structural measures of the integrity of the epileptogenic zone. Methods: We used positron emission tomography (PET) with fluorine IS 2-deoxyglucose to study 91 patients with temporal lobe seizure foci localized by ictal video-EEG. PET was performed in the awake interictal resting state with ears plugged and eyes patched. We recorded surface EEG during injection (5 mCi) and the 30-min uptake period. We used a standard template to analyze PET scans. Results: A significant negative relation was found between the duration of epilepsy and hippocampal glucose metabolism ipsilateral to the epileptic focus. Patients with a history of either any febrile seizures, or complex. or prolonged febrile seizures, did not have greater hypometabolism ipsilateral to the epileptic focus than did patients without a febrile seizure history. We found no effect of generalized tonic-clonic seizure history. Conclusions: Longer epilepsy duration is associated with greater hypometabolism. Suggesting that epilepsy is a progressive disease. C1 NIH, Clin Epilepsy Sect, Bethesda, MD 20892 USA. Childrens Natl Med Ctr, Dept Neurol, Washington, DC 20010 USA. RP Theodore, WH (reprint author), NIH Bldg 10,Room 5N-250, Bethesda, MD 20892 USA. EM theodorw@ninds.nih.gov NR 20 TC 29 Z9 29 U1 0 U2 3 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD MAR PY 2004 VL 45 IS 3 BP 276 EP 279 DI 10.1111/j.0013-9580.2004.51803.x PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 802WG UT WOS:000220193000012 PM 15009230 ER PT J AU Sundstroma, J Sullivan, L Selhub, J Benjamin, EJ D'Agostino, RB Jacques, PF Rosenberg, IH Levy, D Wilson, PWF Vasan, RS AF Sundstroma, J Sullivan, L Selhub, J Benjamin, EJ D'Agostino, RB Jacques, PF Rosenberg, IH Levy, D Wilson, PWF Vasan, RS TI Relations of plasma homocysteine to left ventricular structure and function: the Framingham Heart Study SO EUROPEAN HEART JOURNAL LA English DT Article DE heart failure; left ventricular hypertrophy; left ventricular remodelling; metabolism; echocardiography ID ENDOTHELIAL DYSFUNCTION; HYPERTENSIVE RATS; FOLIC-ACID; DISEASE; RISK; HYPERTROPHY; DETERMINANTS; ASSOCIATION; PRESSURE; FAILURE AB Aims Hyperhomocysteinaemia is a risk factor for congestive heart failure, especially in women. We investigated if homocysteine promotes left ventricular (LV) remodelling. Methods and results We examined cross-sectional relations of plasma total homocysteine to echocardiographic LV structure and function in 2697 Framingham Heart Study participants (mean age 58 years, 58% women) free of heart failure and previous myocardial infarction. Adjusting for age and height, plasma homocysteine was positively related to LV mass, wall thickness, and relative wall thickness in women (p = 0.0004-0.04), but not in men (p = 0.28-0.68). Adjusting additionally for other clinical covariates, the relations of plasma homocysteine to LV mass and wall thickness in women remained statistically significant, but the relation to relative watt thickness became of borderline significance (1.92 g, 0.01 cm, and 0.29% increase, respectively, for a 1-SD increase in ln[homocysteine], p = 0.01-0.08). LV mass and watt thickness were higher in the fourth quartile of plasma homocysteine compared to the lower three in all models in women (p = 0.0003-0.02), but not in men (p = 0.25-0.78). Plasma homocysteine was not related to left atrial. size or LV fractional shortening in either sex. Conclusion In our community-based sample, plasma homocysteine was directly related to LV mass and wall thickness in women but not in men. (C) 2004 The European Society of Cardiology. Published by Elsevier Ltd. All rights reserved. C1 Framingham Heart Dis Epidemiol Study, Framingham, MA 01701 USA. Boston Univ, Sch Med, Dept Prevent Med, Boston, MA 02118 USA. Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02118 USA. Boston Univ, Dept Math, Boston, MA 02215 USA. Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr Aging, Boston, MA 02111 USA. NHLBI, Bethesda, MD 20892 USA. RP Vasan, RS (reprint author), Framingham Heart Dis Epidemiol Study, Framingham, MA 01701 USA. EM vasan@fram.nhlbi.nih.gov RI Sundstrom, Johan/A-6286-2009; OI Sundstrom, Johan/0000-0003-2247-8454; Ramachandran, Vasan/0000-0001-7357-5970; Sullivan, Lisa/0000-0003-0726-7149; Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [N01-HC-25195, 1K24HL04334, 1R01HL67288-01, N01-HV-28178, R01HL71039]; NINDS NIH HHS [5R01-NS-17950] NR 33 TC 64 Z9 75 U1 0 U2 2 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD MAR PY 2004 VL 25 IS 6 BP 523 EP 530 DI 10.1016/j.ehj.2004.01.008 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 812JI UT WOS:000220835400012 PM 15039133 ER PT J AU Misteli, T AF Misteli, T TI Genome function in space and time SO EUROPEAN JOURNAL OF CELL BIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Deutschen-Gesellschaft-fur-Zellbiologie CY MAR 24-27, 2004 CL Berlin, Germany SP Deutsch Gesell Zellbiol C1 NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU URBAN & FISCHER VERLAG PI JENA PA BRANCH OFFICE JENA, P O BOX 100537, D-07705 JENA, GERMANY SN 0171-9335 J9 EUR J CELL BIOL JI Eur. J. Cell Biol. PD MAR PY 2004 VL 83 SU 54 BP 21 EP 21 PG 1 WC Cell Biology SC Cell Biology GA 812EX UT WOS:000220823900009 ER PT J AU Wedig, T Mucke, N Marekov, LN Steinert, PM Aebi, U Herrmann, H AF Wedig, T Mucke, N Marekov, LN Steinert, PM Aebi, U Herrmann, H TI Unravelling the mechanism of vimentin unit-length filament (ULF) formation and intermediate filament (IF) growth SO EUROPEAN JOURNAL OF CELL BIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Deutschen-Gesellschaft-fur-Zellbiologie CY MAR 24-27, 2004 CL Berlin, Germany SP Deutsch Gesell Zellbiol C1 DKFZ, Heidelberg, Germany. NIAMS, NIH, Skin Biol Lab, Bethesda, MD USA. ME Mueller Inst, Biozentrum, Basel, Switzerland. NR 0 TC 0 Z9 0 U1 0 U2 2 PU URBAN & FISCHER VERLAG PI JENA PA BRANCH OFFICE JENA, P O BOX 100537, D-07705 JENA, GERMANY SN 0171-9335 J9 EUR J CELL BIOL JI Eur. J. Cell Biol. PD MAR PY 2004 VL 83 SU 54 BP 49 EP 49 PG 1 WC Cell Biology SC Cell Biology GA 812EX UT WOS:000220823900094 ER PT J AU Wiese, C Rolletschek, A Kania, G Zahanich, I Heubach, J Blyszczuk, P Navarrete-Santos, A Boheler, KR Wobus, AM AF Wiese, C Rolletschek, A Kania, G Zahanich, I Heubach, J Blyszczuk, P Navarrete-Santos, A Boheler, KR Wobus, AM TI Signals from mouse embryonic fibroblasts in vitro reprogram adult intestinal epithelial cells into multipotent nestin-expressing progenitor cells SO EUROPEAN JOURNAL OF CELL BIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Deutschen-Gesellschaft-fur-Zellbiologie CY MAR 24-27, 2004 CL Berlin, Germany SP Deutsch Gesell Zellbiol C1 IPK, In Vitro Differentiat Grp, D-06466 Gatersleben, Germany. Tech Univ Dresden, D-8027 Dresden, Germany. Univ Halle Wittenberg, D-4010 Halle Saale, Germany. NIA, Gerontol Res Ctr, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU URBAN & FISCHER VERLAG PI JENA PA BRANCH OFFICE JENA, P O BOX 100537, D-07705 JENA, GERMANY SN 0171-9335 J9 EUR J CELL BIOL JI Eur. J. Cell Biol. PD MAR PY 2004 VL 83 SU 54 BP 71 EP 71 PG 1 WC Cell Biology SC Cell Biology GA 812EX UT WOS:000220823900159 ER PT J AU Soares, ML Coelho, T Sousa, A Holmgren, GS Saraiva, MJ Kastner, DL Buxbaum, JN AF Soares, ML Coelho, T Sousa, A Holmgren, GS Saraiva, MJ Kastner, DL Buxbaum, JN TI Haplotypes and DNA sequence variation within and surrounding the transthyretin gene: genotype-phenotype correlations in familial amyloid polyneuropathy (V30M) in Portugal and Sweden SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Article DE transthyretin; familial amyloid polyneuropathy; V30M mutation; haplotypes; phenotypic heterogeneity; disease onset ID AGE-OF-ONSET; MUTATION; DISEASE; COMMON AB Familial amyloid polyneuropathy (FAP) is a lethal autosomal dominant disorder in which fibrils derived from mutant forms of transthyretin (TTR), the normal plasma carrier of thyroxine (T4) and retinol-binding protein, are deposited in tissues. Over 80 TTR sequence variants are associated with FAP, but the aminoacid substitutions alone do not completely explain the variability in disease penetrance, pathology and clinical course. To analyze the factors possibly contributing to this phenotypic variability, we characterized the variations within the wild-type and mutant (Val30Met) TTR genes and their flanking sequences by performing extended microsatellite haplotype analyses, sequencing and single-nucleotide polymorphism haplotyping of genomic DNA from Portuguese and Swedish carriers of V30M. We identified 10 new polymorphisms in the TTR untranslated regions, eight resulting from single-base substitutions and two arising from insertion/deletions in dinucleotide repeat sequences. The data suggest that the onset of symptoms of FAP V30M may be modulated by an interval downstream of TTR on the accompanying noncarrier chromosome ( defined by microsatellites D18S457 and D18S456), but not by the immediately 5'- and 3'-flanking sequences of TTR. During the course of these studies, we also encountered the first instance in which the previously described intragenic haplotype III may be associated with V30M FAP in the Portuguese population. C1 Scripps Res Inst, Dept Mol & Expt Med, Div Rheumatol Res, La Jolla, CA 92037 USA. Scripps Res Inst, Dept Mol & Expt Med, WM Keck Autoimmune Dis Ctr, La Jolla, CA 92037 USA. IBMC, Amyloid Unit, Oporto, Portugal. Ctr Estudos Paramiloidose, Oporto, Portugal. IBMC, Neuropsychophysiol Unit, Oporto, Portugal. Inst Ciencias Biomed Abel Salazar, Oporto, Portugal. IBMC, UnIGENe, Oporto, Portugal. Umea Univ, Dept Clin Genet, S-90187 Umea, Sweden. NIAMSD, Genet & Genom Branch, Bethesda, MD 20892 USA. RP Buxbaum, JN (reprint author), Scripps Res Inst, Dept Mol & Expt Med, Div Rheumatol Res, 10550 N Torrey Pines Rd,MEM-230, La Jolla, CA 92037 USA. EM jbux@scripps.edu RI Lima, Marta/C-7042-2009; Saraiva, Maria Joao/K-3907-2013; Sousa, Alda/K-4372-2013 OI Saraiva, Maria Joao/0000-0002-3360-6899; Sousa, Alda/0000-0001-5441-1815 FU NIA NIH HHS [R01 AG19259] NR 25 TC 26 Z9 26 U1 2 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1018-4813 J9 EUR J HUM GENET JI Eur. J. Hum. Genet. PD MAR PY 2004 VL 12 IS 3 BP 225 EP 237 DI 10.1038/sj.ejhg.5201095 PG 13 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 775UA UT WOS:000189078000010 PM 14673473 ER PT J AU Chen, X Murakami, T Oppenheim, JJ Howard, DMZ AF Chen, X Murakami, T Oppenheim, JJ Howard, DMZ TI Differential response of murine CD4(+)CD25(+) and CD4(+)CD25(-) T cells to dexamethasone-induced cell death SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE dexamethasone; T cell; CD4(+)CD25(+); cell death ID GLUCOCORTICOID-INDUCED APOPTOSIS; INDUCED TNF RECEPTOR; VERSUS-HOST DISEASE; REGULATORY CELLS; 1-ALPHA,25-DIHYDROXYVITAMIN D-3; GENE-EXPRESSION; MICE; POPULATION; ACTIVATION; TOLERANCE AB To evaluate the in vivo effect of immunosuppressive glucocorticoids on CD4(+)CD25(+) T regulatory cells, we injected dexamethasone (Dex) into BALB/c mice. Administration of Dex enhanced the proportion of CD4(+)CD25(+) cells and the ratio of CD4(+)CD25(+) cells to CD4(+)CD25(-) cells in the lymphoid organs, especially in the thymus. This correlates with our in vitro observation that CD4(+)CD25(+) T cells express higher levels of glucocorticoid receptor and Bcl-2, and are therefore more resistant to Dex-mediated cell death than CD4(+)CD25(-) T cells. Furthermore, IL-2 selectively protected CD4(+)CD25(-) T cells from Dex-induced cell death, while IL-7 and IL-15 did not exert preferential protective effects. Dex-treated CD4(+)CD25(+) T cells expressed higher levels of intracellular CTLA-4 and surface glucocorticoid-induced TNF receptor than fresh CD4(+)CD25(+) T cells, but still failed to respond to TCR stimulation and inhibited proliferation of CD4(+)CD25(-) T cells. These results suggest that, in addition to suppressing cytokine transcription, Dex treatment is permissive for the survival of functional CD4(+)CD25(-) T regulatory cells, and this property may contribute to the anti-inflammatory and immunosuppressive efficacy of glucocorticoids. Our data also suggest that selective protection of CD4(+)CD25(+) T cell from apoptosis may constitute a role in immune tolerance for IL-2. C1 NCI, Mol Immunoregulat Lab, Ctr Canc Res, Ft Detrick, MD 21702 USA. SAIC Frederick Inc, Basic Res Program, Frederick, MD USA. RP Howard, DMZ (reprint author), NCI, Mol Immunoregulat Lab, Ctr Canc Res, POB B,Bldg 560,Room 31-19, Ft Detrick, MD 21702 USA. EM howardz@mail.ncifcrf.gov RI Howard, O M Zack/B-6117-2012; Chen, Xin/I-6601-2015 OI Howard, O M Zack/0000-0002-0505-7052; Chen, Xin/0000-0002-2628-4027 FU NCI NIH HHS [N01-CO-12400] NR 42 TC 113 Z9 132 U1 0 U2 1 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD MAR PY 2004 VL 34 IS 3 BP 859 EP 869 DI 10.1002/eji.2003.24506 PG 11 WC Immunology SC Immunology GA 802WH UT WOS:000220193100027 PM 14991616 ER PT J AU Lobito, AA Lopes, MF Lenardo, MJ AF Lobito, AA Lopes, MF Lenardo, MJ TI Ectopic T cell receptor expression causes B cell immunodeficiency in transgenic mice SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE TCR transgenic; ER stress; B cell development; apoptosis ID LOCUS-CONTROL REGION; MOUSE BONE-MARROW; BETA-CHAIN GENES; ENDOPLASMIC-RETICULUM; ANTIGEN RECEPTOR; NEGATIVE SELECTION; ALPHA/DELTA LOCUS; ALPHA-CHAIN; AUTOIMMUNITY; DEGRADATION AB Mice expressing transgenic T cell receptors (TCR) are used to explore important questions in immunity. However, transgene expression may have unexpected effects. We previously reported a B cell immunodeficiency, comprising decreased B cell numbers and diminished antibody responses, in mice that express a transgenic TCR specific for nicotinic acetylcholine receptor; the mice were generated using cassette vectors designed specifically for transgenic TCR expression [see Kouskoff et al. J. Immunol. Methods 1995. 180: 273-280]. We now show data suggesting that this defect is due to the expression and accumulation of TCR alpha and beta chains inside B cells and induction of an endoplasmic reticulum stress response, causing apoptosis at the pre B-I and later B cell stage. Thus, inappropriate transgene expression can profoundly affect B cells, leading to a previously undescribed mechanism of immunodeficiency. C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Lenardo, MJ (reprint author), NIAID, Immunol Lab, NIH, Bldg 10,Room 11N311,10 Ctr Dr, Bethesda, MD 20892 USA. EM lenardo@nih.gov RI lopes, marcela/E-2201-2012 OI lopes, marcela/0000-0002-4508-0505 NR 33 TC 2 Z9 2 U1 0 U2 0 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD MAR PY 2004 VL 34 IS 3 BP 890 EP 898 DI 10.1002/eji.200324675 PG 9 WC Immunology SC Immunology GA 802WH UT WOS:000220193100030 PM 14991619 ER PT J AU Sonntag, KC Simantov, R Kim, KS Isacson, O AF Sonntag, KC Simantov, R Kim, KS Isacson, O TI Temporally induced Nurr1 can induce a non-neuronal dopaminergic cell type in embryonic stem cell differentiation SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE dopaminergic; ES cell differentiation; J1-rtTA; Nurr1; Tet-system ID ORPHAN NUCLEAR RECEPTOR; TYROSINE-HYDROXYLASE GENE; IN-VITRO; TRANSGENE EXPRESSION; ADENOVIRAL VECTORS; PARKINSONS-DISEASE; PROGENITOR CELLS; RESPONSE ELEMENT; MAMMALIAN-CELLS; CULTURED-CELLS AB The nuclear transcription factor Nurr1 is involved in the development and maintenance of the midbrain dopaminergic (DA) neuronal phenotype. We analysed the cellular and biological effects of Nurr1 during embryonic stem (ES) cell differentiation using the ROSA26-engineered Tet-inducible ES cell line J1-rtTA that does not express transgenes in mature neurons. Induction of Nurr1 at nestin-positive precursor and later stages of ES cell differentiation produced a non-neuronal DA cell type including functional DA transporters. In these cells, we found a clear correlation between Nurr1 and TH gene expression and specific midbrain DA cellular markers such as AADC, AHD2 and calbindin. Nurr1 did not alter gene expression of non-DA neuronal phenotypes and did not influence other midbrain developmental transcription factors, such as Otx1, Otx2, En-1, GBX2, Pitx3 and lmx1b. In addition, Nurr1 expression was required for maintenance of the DA phenotype and mediated up-regulation of the tyrosine kinase Ret and associated trophic factor GDNF-family receptors alpha 1, 2, and 4. This demonstrates that Nurr1 is sufficient to induce and maintain a midbrain-like DA biochemical and functional cellular phenotype independent of neurogenesis. C1 Harvard Univ, Sch Med, Neuroregenerat Labs, McLean Hosp, Belmont, MA 02478 USA. Harvard Univ, Sch Med, Udall Parkinsons Dis Res Ctr Excellence, McLean Hosp, Belmont, MA 02478 USA. Harvard Univ, Sch Med, Mol Neurobiol Lab, McLean Hosp, Belmont, MA 02478 USA. RP Isacson, O (reprint author), Harvard Univ, Sch Med, Neuroregenerat Labs, McLean Hosp, MRC 120,115 Mill St, Belmont, MA 02478 USA. EM isacson@hms.harvard.edu FU NIMH NIH HHS [MH48866, R01 MH048866, R29 MH048866]; NINDS NIH HHS [P50 NS039793, P50 NS039793-05]; PHS HHS [P50 N539793] NR 54 TC 60 Z9 64 U1 0 U2 3 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD MAR PY 2004 VL 19 IS 5 BP 1141 EP 1152 DI 10.1111/j.1460-9568.2004.03204.x PG 12 WC Neurosciences SC Neurosciences & Neurology GA 802QA UT WOS:000220176800003 PM 15016073 ER PT J AU Wrenn, CC Kinney, JW Marriott, LK Holmes, A Harris, AP Saavedra, MC Starosta, G Innerfield, CE Jacoby, AS Shine, J Iismaa, TP Wenk, GL Crawley, JN AF Wrenn, CC Kinney, JW Marriott, LK Holmes, A Harris, AP Saavedra, MC Starosta, G Innerfield, CE Jacoby, AS Shine, J Iismaa, TP Wenk, GL Crawley, JN TI Learning and memory performance in mice lacking the GAL-R1 subtype of galanin receptor SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE conditioned fear; knockout; learning; social transmission of food preference; memory; water maze ID OVEREXPRESSING TRANSGENIC MICE; NICTITATING-MEMBRANE RESPONSE; ALZHEIMERS-DISEASE; PHARMACOLOGICAL CHARACTERIZATION; MOLECULAR-CLONING; MESSENGER-RNA; BEHAVIORAL CHARACTERIZATION; FUNCTIONAL-CHARACTERIZATION; GENOMIC ORGANIZATION; FEEDING-BEHAVIOR AB The neuropeptide galanin induces performance deficits in a wide range of cognitive tasks in rodents. Three G-protein-coupled galanin receptor subtypes, designated GAL-R1, GAL-R2 and GAL-R3, have been cloned. The present study examined the role of GAL-R1 in cognition by testing mice with a null mutation in Galr1 on several different types of learning and memory tasks. Assessments of general health, neurological reflexes, sensory abilities and motor functions were conducted as control measures. Mutant mice were unimpaired in social transmission of food preference and the Morris water maze. In tests of fear conditioning, mutant mice were unimpaired in a delay version of cued fear conditioning. However, mice homozygous for the null mutation were impaired in a trace version of cued fear conditioning. Mutant mice were unimpaired in contextual fear conditioning, whether training was by the delay or trace protocol. General health, neurological reflexes, sensory abilities and motor functions did not differ across genotypes, indicating that the trace fear conditioning deficit was not an artifact of procedural disabilities. The findings of normal performance on several cognitive tasks and a selective deficit in trace cued fear conditioning in homozygous GAL-R1 mutant mice are discussed in terms of hypothesized roles of the GAL-R1 subtype. The generally normal phenotype of GAL-R1 null mutants supports the use of this line for identification of the receptor subtypes that mediate the cognitive deficits produced by exogenous galanin. C1 NIMH, Lab Behav Neurosci, Bethesda, MD 20892 USA. Univ Arizona, Div Neural Syst Memory & Ageing, Tucson, AZ USA. St Vincents Hosp, Garvan Inst Med Res, Sydney, NSW 2010, Australia. RP Wrenn, CC (reprint author), NIMH, Lab Behav Neurosci, Bethesda, MD 20892 USA. EM wrennc@intra.nimh.nih.gov OI Marriott, Lisa/0000-0001-6390-3053 FU NIA NIH HHS [AG10546] NR 91 TC 52 Z9 54 U1 2 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD MAR PY 2004 VL 19 IS 5 BP 1384 EP 1396 DI 10.1111/j.1460.9568.2004.03214.x PG 13 WC Neurosciences SC Neurosciences & Neurology GA 802QA UT WOS:000220176800026 PM 15016096 ER PT J AU von Buchholtz, L Elischer, A Tareilus, E Gouka, R Kaiser, C Breer, H Conzelmann, S AF von Buchholtz, L Elischer, A Tareilus, E Gouka, R Kaiser, C Breer, H Conzelmann, S TI RGS21 is a novel regulator of G protein signalling selectively expressed in subpopulations of taste bud cells SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE bitter; Rattus norvegicus; RGS protein; signal transduction; sweet ID GTPASE-ACTIVATING PROTEINS; SWEET TASTE; BITTER TASTE; ALPHA-GUSTDUCIN; INOSITOL 1,4,5-TRISPHOSPHATE; MAMMALIAN SWEET; RECEPTOR-CELLS; UMAMI TASTE; TRANSDUCTION; FAMILY AB G-protein-mediated signalling processes are involved in sweet and bitter taste transduction. In particular, the G protein a-subunit gustducin has been implicated in these processes. One of the limiting factors for the time-course of cellular responses induced by tastants is therefore the intrinsic GTPase activity of a-gustducin, which determines the lifetime of the active G protein complex. In several signalling systems specific 'regulator of G protein signalling' (RGS) proteins accelerate the GTPase activity of G protein alpha-subunits. Using differential screening approaches, we have identified a novel FIGS protein termed RGS21, which represents the smallest known member of this protein family. Reverse transcription polymerase chain reaction and in situ hybridization experiments demonstrated that RGS21 is expressed selectively in taste tissue where it is found in a subpopulation of sensory cells. Furthermore, it is coexpressed in individual taste cells with bitter and sweet transduction components including a-gustducin, phospholipase Cbeta2, T1R2/ T1R3 sweet taste receptors and T2R bitter taste receptors. In vitro binding assays demonstrate that RGS21 binds U-gustducin in a conformation-dependent manner and has the potential to interact with the same Galpha subtypes as T1R receptors. These results suggest that RGS21 could play a regulatory role in bitter as well as sweet taste transduction processes. C1 Univ Hohenheim, Inst Physiol, D-70599 Stuttgart, Germany. Unilever Res Labs Vlaardingen, NL-3130 AC Vlaardingen, Netherlands. LION Biosci, D-69120 Heidelberg, Germany. RP von Buchholtz, L (reprint author), NIH, 10 Ctr Dr,MSC 1188, Bethesda, MD 20892 USA. EM lars@von-buchholtz.com NR 55 TC 15 Z9 15 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD MAR PY 2004 VL 19 IS 6 BP 1535 EP 1544 DI 10.1111/j.1460-9568.2004.03257.x PG 10 WC Neurosciences SC Neurosciences & Neurology GA 807RV UT WOS:000220519500011 PM 15066150 ER PT J AU McCrae, RR Costa, PT Hrebickova, M Urbanek, T Martin, TA Oryol, VE Rukavishnikov, AA Senin, IG AF McCrae, RR Costa, PT Hrebickova, M Urbanek, T Martin, TA Oryol, VE Rukavishnikov, AA Senin, IG TI Age differences in personality traits across cultures: Self-report and observer perspectives SO EUROPEAN JOURNAL OF PERSONALITY LA English DT Article; Proceedings Paper CT Annual Convention of the American-Psychological-Association CY 2003 CL Toronto, CANADA SP Amer Psychol Assoc ID LIFE-SPAN; ADULTHOOD; STABILITY AB Using self-report measures, longitudinal studies in the US and cross-sectional studies from many cultures suggest that the broad factors of Neuroticism, Extraversion, and Openness to Experience decline. from adolescence to adulthood, whereas Agreeableness and Conscientiousness increase. Data are inconsistent on the rate of change during adulthood, and on the generalizability of self-report findings to informant ratings. We analysed cross-sectional data from self-reports and informant ratings on the Revised NEO Personality Inventory in Czech (N = 705) and Russian (N = 800) samples. Some curvilinear effects were found, chiefly in the Czech sample; informant data generally replicated self-reports, although the, effects were weaker. Although many of the details are not yet clear there appear to be pan-cultural trends in personality development that are consistent with the hypothesis of intrinsic maturation. Copyright (C) 2004 John Wiley Sons, Ltd. C1 Yaroslavl State Univ, Yaroslavl, Russia. Susquehanna Univ, Selinsgrove, PA USA. Acad Sci Czech Republ, Inst Psychol, Brno, Czech Republic. NIA, NIH, DHHS, Baltimore, MD 21224 USA. RP McCrae, RR (reprint author), Gerontol Res Ctr, Box 03,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM jeffm@lpc.grc.nia.nih.gov RI Urbanek, Tomas/G-9427-2014; Hrebickova, Martina/H-4410-2014; OI Urbanek, Tomas/0000-0002-8807-4869; Hrebickova, Martina/0000-0003-4356-567X; Costa, Paul/0000-0003-4375-1712 NR 28 TC 43 Z9 43 U1 0 U2 7 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0890-2070 J9 EUR J PERSONALITY JI Eur. J. Personal. PD MAR PY 2004 VL 18 IS 2 BP 143 EP 157 DI 10.1002/per.510 PG 15 WC Psychology, Social SC Psychology GA 811BC UT WOS:000220746400005 ER PT J AU Hardy, J AF Hardy, J TI Genetic evidence that the amounts of pathogenic proteins matter in the pathogeneses of Alzheimer's and Parkinson's diseases SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT Workshop on Neuropsychopharmacology for Young Scientific in Europe CY MAR 12-14, 2004 CL Nice, FRANCE SP European Coll Neuropsychopharmcol RP Hardy, J (reprint author), NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD MAR PY 2004 VL 14 SU 1 BP S1 EP S1 DI 10.1016/S0924-977X(04)90000-4 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 805OT UT WOS:000220376300002 ER PT J AU De Cabo, R Cabello, R Rios, M Lopez-Lluch, G Ingram, DK Lane, MA Navas, P AF De Cabo, R Cabello, R Rios, M Lopez-Lluch, G Ingram, DK Lane, MA Navas, P TI Calorie restriction attenuates age-related alterations in the plasma membrane antioxidant system in rat liver SO EXPERIMENTAL GERONTOLOGY LA English DT Article DE caloric restriction; coenzyme Q; plasma membrane ID OXIDATIVE DNA-DAMAGE; COENZYME-Q; LIFE-SPAN; VITAMIN-E; SACCHAROMYCES-CEREVISIAE; ASCORBATE STABILIZATION; ELECTRON-TRANSPORT; FOOD RESTRICTION; SKELETAL-MUSCLE; CELLS AB Aging is associated with increased production of reactive oxygen species and oxidation-induced damage to intracellular structures and membranes. Caloric restriction (CR) is the only non-genetic method proven to extend lifespan in mammals. Although the mechanisms of CR remain to be clearly elucidated, reductions in oxidative stress have been shown to increase lifespan in several model systems. Oxidative stress can be attenuated by CR. Mitochondria and plasma membrane (PM) are normal sources of free radicals. The PM has a trans-membrane redox system that provides electrons to recycle lipophilic antioxidants, such as alpha-tocopherol and coenzyme Q (CoQ). The idea developed in this study is that the PM is intimately involved in cellular physiology controlling the relationship of the cell to its environment. PM is the key for protecting cellular integrity during aging. Specifically, we have investigated age-related alterations and the effects of CR in the trans-PM redox (antioxidant) system in rat liver. We found that age-related declines in the ratio of CoQ(10)/CoQ(9) and alpha-tocopherol in liver PM were attenuated by CR compared to those fed ad libitum (AL). CoQ-dependent NAD(P)H dehydrogenases were increased in CR old rat liver PMs. As a consequence, the liver PM of CR old rats was more resistant to oxidative stress-induced lipid peroxidation than AL rats. Thus, our results suggest that CR induces a higher capacity to oxidize NAD(P)H in the PM of old rat livers and as a result, a higher resistance to oxidative stress-induced damage. (C) 2004 Elsevier Inc. All rights reserved. C1 NIA, Lab Expt Gerontol, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. Univ Pablo Olavide, Ctr Andaluz Biol Desarrollo, Seville 41013, Spain. RP De Cabo, R (reprint author), NIA, Lab Expt Gerontol, Gerontol Res Ctr, NIH, Box 10,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM decabora@grc.nia.nih.gov RI de Cabo, Rafael/E-7996-2010; Lopez-Lluch, Guillermo/N-4742-2014; de Cabo, Rafael/J-5230-2016; OI Lopez-Lluch, Guillermo/0000-0001-9830-8502; de Cabo, Rafael/0000-0002-3354-2442; , rafael/0000-0003-2830-5693 NR 41 TC 79 Z9 79 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0531-5565 J9 EXP GERONTOL JI Exp. Gerontol. PD MAR PY 2004 VL 39 IS 3 BP 297 EP 304 DI 10.1016/j.exger.2003.12.003 PG 8 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 804DJ UT WOS:000220279100003 PM 15036389 ER PT J AU Plasilova, M Risitano, AM O'Keefe, CL Rodriguez, A Wlodarski, M Young, NS Maciejewski, J AF Plasilova, M Risitano, AM O'Keefe, CL Rodriguez, A Wlodarski, M Young, NS Maciejewski, J TI Shared and individual specificities of immunodominant cytotoxic T-cell clones in paroxysmal nocturnal hemoglobinuria as determined by molecular analysis SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID MARROW FAILURE SYNDROMES; V-BETA REPERTOIRE; APLASTIC-ANEMIA; BONE-MARROW; FLOW-CYTOMETRY; MYELODYSPLASTIC SYNDROME; CDR3 MOTIFS; IN-VITRO; LYMPHOCYTES; TCR AB Objective. Similar immune mechanisms have been suggested to operate in aplastic anemia (AA) and paroxysmal nocturnal hemoglobinuria (PNH), and the presence of PNH clones in AA may indicate that an immune reaction directed against hematopoietic stem cells may be responsible for the immune selection pressure leading to PNH evolution. We previously described expansions of selective cytotoxic T-lymphocyte (CTL) clones in AA patients. Materials and Methods. We applied a molecular analysis of the T-cell receptor repertoire to study the characteristics of CTL response in patients with various forms of PNH. Immunodominant T-cell clones were detected using combined flow cytometric and molecular analysis of the variable beta (VB) chain and CDR3 representation, followed by determination of the frequency of individual CDR3 clonotypes. Clonotypic polymerase chain reaction (PCR) was performed to establish clonotypic utilization pattern. Results. In patients with a past history of AA, and when subgrouped by current blood counts as "hypoproliferative" PNH patients (in contrast to purely hemolytic form of PNH), more pronounced skewing of VB family utilization was found, consistent with T-cell responses involving several immunodominant CTL clones. Sequences of the PNH-derived clonotypes were used to design PCR-based assays for the utilization analysis of individual clones in PNH patients. The clonotypic distribution pattern established by this PCR method indicated that immunodominant T-cell specificities were shared between some patients but also may be found at low frequencies in controls. Conclusion. Analysis of the CDR3 sequence pattern as a marker for expanded immunodominant clonotypes may have an application in the study of T-cell responses in PNH. (C) 2004 International Society for Experimental Hematology. Published by Elsevier Inc. C1 Cleveland Clin Fdn, Expt Hematol & Hematopoiesis Sect, Taussig Canc Ctr, Cleveland, OH 44195 USA. Univ Naples Federico II, Div Hematol, Naples, Italy. NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Maciejewski, J (reprint author), Cleveland Clin Fdn, Expt Hematol & Hematopoiesis Sect, Taussig Canc Ctr, 9500 Euclid Ave,R40, Cleveland, OH 44195 USA. EM maciejj@cc.ccf.org OI Wlodarski, Marcin/0000-0001-6638-9643 FU NHLBI NIH HHS [R01 HL073429-01A1] NR 43 TC 15 Z9 17 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD MAR PY 2004 VL 32 IS 3 BP 261 EP 269 DI 10.1016/j.exphem.2003.11.011 PG 9 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 814HK UT WOS:000220965600004 PM 15003311 ER PT J AU Sodhi, A Montaner, S Gutkind, JS AF Sodhi, A Montaner, S Gutkind, JS TI Does dysregulated expression of a deregulated viral GPCR trigger Kaposi's sarcomagenesis? SO FASEB JOURNAL LA English DT Article DE Kaposi's sarcoma-associated herpesvirus; human herpesvirus-8; G-protein-coupled receptor; HIV ID PROTEIN-COUPLED RECEPTOR; NF-KAPPA-B; CONSTITUTIVE ACTIVITY; ENDOTHELIAL-CELLS; HERPESVIRUS; ACTIVATION; INFECTION; KINASE; INTERLEUKIN-8; ANGIOGENESIS AB In 1994, the Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8) was identified as the etiologic agent of Kaposi's sarcoma (KS). KSHV has since been associated with two additional AIDS-related malignancies: primary effusion lymphomas (PEL) and multicentric Castleman's disease (MCD). Although molecular characterization of the KSHV genome has revealed several candidate oncogenes, infection with KSHV alone is not sufficient to cause KS, suggestive of an accomplice in KS initiation. Recent experimental evidence supports a key role for a particular KSHV gene, a constitutively-active G-protein-coupled receptor (vGPCR), in the development of KS. However, it is unclear how a lytic gene expressed in cells destined to die can cause cancer. Here we propose that dysregulation of the viral gene program may lead to nonlytic vGPCR expression. Several candidate cofactors (e.g., HIV-1 Tat, inflammation, aborted lytic cycle progression) are identified that may trigger vGPCR dysregulation, enabling oncogenic signaling pathways up-regulated by vGPCR, combined with the paracrine secretions from vGPCR-expressing cells, to promote the initiation of KS. If KS is indeed dependent on vGPCR dysregulation, then the development of new therapeutic modalities specifically targeting this viral protein or its downstream targets may ultimately prove to be the most effective treatment strategy for this enigmatic disease. C1 Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA. RP Sodhi, A (reprint author), NIDR, Cell Growth Regulat Sect, Oral & Pharyngeal Canc Branch, NIH, 30 Convent Dr,Bldg 30,Room 211, Bethesda, MD 20892 USA. EM asodhi@nidcr.nih.gov; sg39v@nih.gov RI Gutkind, J. Silvio/A-1053-2009 NR 33 TC 47 Z9 50 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR PY 2004 VL 18 IS 3 BP 422 EP 427 DI 10.1096/fj.03-1035hyp PG 6 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 807TC UT WOS:000220522800035 PM 15003988 ER PT J AU Andringa, G Lam, KY Chegary, M Wang, X Chase, TN Bennett, MC AF Andringa, G Lam, KY Chegary, M Wang, X Chase, TN Bennett, MC TI Tissue trans glutaminase catalyzes the formation of alpha-synuclein crosslinks in Parkinson's disease SO FASEB JOURNAL LA English DT Article DE crosslinking; protein aggregation; human; brain; substantia nigra ID ALZHEIMERS-DISEASE; BODY FORMATION; LEWY BODIES; TRANSGLUTAMINASE; PROTEIN; FIBRINOGEN; MEMBRANE; STABILIZATION; AGGREGATION; PATHOLOGY AB In Parkinson's disease (PD), conformational changes in the alpha-synuclein monomer precede the formation of Lewy bodies. We examined postmortem PD and undiseased (control) substantia nigra for evidence of pathological crosslinking of alpha-synuclein by tissue transglutaminase (tTG) using immunohistochemistry, immunoprecipitation, and Western blot. Consistent with previous reports, we found that both tTG and its substrate-characteristic N-epsilon-(gamma-glutamyl)-lysine crosslink are increased in PD nigral dopamine neurons. Furthermore, both the tTG protein and its substrate crosslink coprecipitated with alpha-synuclein in extracts of PD substantia nigra. Unexpectedly, the isodipeptide crosslink was detected in the alpha-synuclein monomer as well as in higher molecular mass oligomers of alpha-synuclein. Although the intramolecularly crosslinked alpha-synuclein monomer was present in control tissue, it was highly enriched in PD substantia nigra. Conversely, significantly less uncrosslinked alpha-synuclein remained in the postimmunoprecipitate lysate of PD tissue than in control. Crosslinked alpha-synuclein, formed at the expense of the total alpha-synuclein monomer, correlated with disease progression. These results demonstrate that much of the alpha-synuclein monomer in PD nigra is crosslinked by tTG and thus may be functionally impaired. This modification appears to be an early step in PD pathogenesis, preceding the aggregation of alpha-synuclein in Lewy bodies. C1 Natl Inst Neurol Disorders & Stroke, Expt Therapeut Branch, NIH, Bethesda, MD 20892 USA. Blanchette Rockefeller Neurosci Inst, Rockville, MD USA. RP Chase, TN (reprint author), Natl Inst Neurol Disorders & Stroke, Expt Therapeut Branch, NIH, Bldg 10,Room 5C-103, Bethesda, MD 20892 USA. EM Chaset@ninds.nih.gov NR 39 TC 76 Z9 76 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR PY 2004 VL 18 IS 3 BP 932 EP + DI 10.1096/fj.03-0829fje PG 28 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 807TC UT WOS:000220522800031 PM 15001552 ER PT J AU Baird, DD AF Baird, DD TI More than one fertile ovulation per cycle? SO FERTILITY AND STERILITY LA English DT Letter C1 NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. RP Baird, DD (reprint author), NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. OI Baird, Donna/0000-0002-5544-2653 NR 3 TC 1 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 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD MAR PY 2004 VL 81 IS 3 BP 729 EP 729 DI 10.1016/j.fertnstert.2003.12.003 PG 1 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 802RJ UT WOS:000220180300056 PM 15037442 ER PT J AU Bezrukov, SM AF Bezrukov, SM TI Noise analysis in studies of protein dynamics and molecular transport SO FLUCTUATION AND NOISE LETTERS LA English DT Article DE ion channels; single molecules; fluctuations; bacterial porins ID PARTICLE NUMBER FLUCTUATIONS; STOCHASTIC RESONANCE; MEMBRANE CHANNEL; ION-CHANNEL; KINETICS; BINDING; PORES; CONDUCTANCE; MALTOPORIN; POLYMERS AB Understanding the role of noise at cellular and higher hierarchical levels depends on our knowledge of the physical mechanism of its generation. Conversely, noise is a rich source of information about these mechanisms. Using channel-forming protein molecules reconstituted into artificial 5-nm thick insulating lipid films, it is possible to investigate noise in single-molecule experiments and to relate its origins to protein function. Recent progress in this field is reviewed with an emphasis on how this experimental technique can be used to study low-frequency protein dynamics, including not only reversible ionization of sites on the channel-forming protein molecule, but also molecular mechanisms of 1/f-noise generation. Several new applications of the single-molecule noise analysis to membrane transport problems are also addressed. Among those is a study on antibiotic translocation across bacterial walls. High-resolution recording of ionic current through the single channel, formed by the general bacterial porin, OmpF, enables us to resolve single-molecule events of antibiotic translocation. C1 NICHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. RP Bezrukov, SM (reprint author), NICHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. EM bezrukov@helix.nih.gov NR 34 TC 6 Z9 6 U1 0 U2 0 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA JOURNAL DEPT PO BOX 128 FARRER ROAD, SINGAPORE 912805, SINGAPORE SN 0219-4775 J9 FLUCT NOISE LETT JI Fluct. Noise Lett. PD MAR PY 2004 VL 4 IS 1 BP L23 EP L31 DI 10.1142/S0219477504001641 PG 9 WC Mathematics, Interdisciplinary Applications; Physics, Applied SC Mathematics; Physics GA 831OU UT WOS:000222204900004 ER PT J AU Stewart, GS Fenton, RA Thevenod, F Smith, CP AF Stewart, GS Fenton, RA Thevenod, F Smith, CP TI Urea movement across mouse colonic plasma membranes is mediated by UT-A urea transporters SO GASTROENTEROLOGY LA English DT Article ID RAT-KIDNEY; NITROGEN-BALANCE; NORMAL MEN; PROTEIN; LOCALIZATION; CLONING; COTRANSPORTER; EXPRESSION; SALVAGE; TESTIS AB Background&Aims: Urea is a major nitrogen source for commensal bacteria that inhabit the large intestine. UT-A urea transporters mediate urea movement across plasma membranes. The aim of this study was to determine whether UT-A proteins are expressed in the mouse colon and, if so, whether they have a functional role in transcellular urea transport. Methods: Mouse colonic UT-A transporters were investigated with Northern blot analysis, immunoblotting, immunolocalization, and refractive light flux experiments. Results: Northern blot analysis showed that 4 UT-A transcripts were present in mouse colon. Two peptide-targeted-polyclonal antibodies showed the presence of UT-A immunoreactive proteins in mouse colon. Antiserum ML446 targeted to the N-terminus of mouse UT-A1 detected proteins of 34 and 48 kilodaltons. Antiserum ML194 targeted to the C-terminus of mouse UT-A1 detected proteins of 48, 75, and 100 kilodaltons. Immunolocalization studies using ML446 showed the presence of UT-A proteins in cells throughout the colonic crypts. ML194 specifically stained cells located in the proliferative and stem regions of the lower portion of colonic crypts. Differential centrifugation and immunoblotting of colonic epithelia showed that UT-A proteins were present in plasma membrane-enriched fractions. Refractive light flux experiments using colonic plasma membrane vesicles showed a significant urea flux, which was completely inhibited by the UT-A inhibitor phloretin. Conclusions: Functional UT-A transporters are expressed in the plasma membranes of mouse colon, indicating that these proteins may play a key role in host/bacterial interaction. C1 Univ Manchester, Sch Biol Sci, Manchester M13 9PT, Lancs, England. NHLBI, Kidney & Electrolyte Metab Lab, Bethesda, MD 20892 USA. Univ Witten Herdecke, Dept Physiol, Witten, Germany. RP Smith, CP (reprint author), Univ Manchester, Sch Biol Sci, G-38,Stopford Bldg,Oxford Rd, Manchester M13 9PT, Lancs, England. EM cpsmith@man.ac.uk NR 33 TC 19 Z9 20 U1 0 U2 5 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 MAR PY 2004 VL 126 IS 3 BP 765 EP 773 DI 10.1053/j.gastro.2003.11.045 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 802RC UT WOS:000220179600020 PM 14988831 ER PT J AU Sedegah, M Charoenvit, Y Minh, L Belmonte, M Majam, VF Abot, S Ganeshan, H Kumar, S Bacon, DJ Stowers, A Narum, DL Carucci, DJ Rogers, WO AF Sedegah, M Charoenvit, Y Minh, L Belmonte, M Majam, VF Abot, S Ganeshan, H Kumar, S Bacon, DJ Stowers, A Narum, DL Carucci, DJ Rogers, WO TI Reduced immunogenicity of DNA vaccine plasmids in mixtures SO GENE THERAPY LA English DT Article DE DNA vaccine; Plasmodium falciparum; multivalent vaccine ID ANTIGENIC-COMPETITION; T-CELL; PROTECTIVE EFFICACY; IMMUNE-RESPONSE; MALARIA; IMMUNIZATION; PROTEIN; EXPRESSION; MULTISTAGE; INDUCTION AB We measured the ability of nine DNA vaccine plasmids encoding candidate malaria vaccine antigens to induce antibodies and interferon-gamma responses when delivered alone or in a mixture containing all nine plasmids. We further examined the possible immunosuppressive effect of individual plasmids, by assessing a series of mixtures in which each of the nine vaccine plasmids was replaced with a control plasmid. Given alone, each of the vaccine plasmids induced significant antibody titers and, in the four cases for which appropriate assays were available, IFN-gamma responses. Significant suppression or complete abrogation of responses were seen when the plasmids were pooled in a nine-plasmid cocktail and injected in a single site. Removal of single genes from the mixture frequently reduced the observed suppression. Boosting with recombinant poxvirus increased the antibody response in animals primed with either a single gene or the mixture, but, even after boosting, responses were higher in animals primed with single plasmids than in those primed with the nine-plasmid mixture. Boosting did not overcome the suppressive effect of mixing for IFN-gamma responses. Interactions between components in a multiplasmid DNA vaccine may limit the ability to use plasmid pools alone to induce responses against multiple targets simultaneously. C1 US Med Res Unit 3, Dept State, Washington, DC 20521 USA. US Med Res Ctr, Malaria Program, Silver Spring, MD USA. Univ Maryland, Sch Med, Dept Microbiol, Baltimore, MD USA. NIAID, Parasit Dis Lab, NIH, Bethesda, MD USA. EntreMed Inc, Rockville, MD USA. RP Rogers, WO (reprint author), US Med Res Unit 3, Dept State, 2020 Accra Pl, Washington, DC 20521 USA. RI Belmonte, Maria/A-8032-2011 NR 20 TC 62 Z9 62 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0969-7128 J9 GENE THER JI Gene Ther. PD MAR PY 2004 VL 11 IS 5 BP 448 EP 456 DI 10.1038/sj.gt.3302139 PG 9 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 774WE UT WOS:000189008600004 PM 14973538 ER PT J AU Pastorino, S Carta, L Puppo, M Melillo, G Bosco, MC Varesio, L AF Pastorino, S Carta, L Puppo, M Melillo, G Bosco, MC Varesio, L TI Picolinic acid- or desferrioxamine-inducible autocrine activation of macrophages engineered to produce IFN gamma: an approach for gene therapy SO GENE THERAPY LA English DT Article DE picolinic acid; macrophages; interferon-gamma; desferrioxamine; shuttle vectors ID HYPOXIA-RESPONSIVE ELEMENT; OXIDE SYNTHASE PROMOTER; RETROVIRAL VECTOR; INTERFERON-GAMMA; EXPRESSION; CELLS; TRYPTOPHAN; CATABOLITE; INDUCTION; PATHWAY AB Macrophage (Mphi)-based vectors are highly mobile cellular shuttles designed to deliver therapeutic genes within the tissues. We engineered a mouse Mf cell line to express the murine interferon-gamma (IFNgamma) under the control of an inducible promoter containing the hypoxia-responsive element, which can be triggered by hypoxia and other stimuli. We show that this Mphi vector can be induced to produce IFNgamma under normoxic conditions by stimulation with picolinic acid (PA), a catabolite of tryptophan, or desferrioxamine (DFX), an iron-chelating drug. The Mphi vector responds to IFNgamma with the induction of IRF-1 and of other IFNgamma-inducible genes, the expression of Ia antigens and induction of phagocytic activity. Inducible nitric oxygen synthase gene expression, nitric oxide production, as well as TNFalpha secretion were enhanced by PA or DFX as the sole stimuli. None of the above responses could be triggered individually by PA or DFX in control, normal Mphi, indicating that the Mphi vector overcame the need for costimulatory molecules derived from the immune system for its full activation. Furthermore, we demonstrate that extracellular iron can downregulate such response, thereby identifying an additional tool for the fine tuning of the Mphi vector response to stimulation. C1 G Gaslini Inst Children, Mol Biol Lab, I-16147 Genoa, Italy. NCI, DTP Tumor Hypoxia Program, NIH, Frederick, MD 21701 USA. RP Varesio, L (reprint author), G Gaslini Inst Children, Mol Biol Lab, Lgo G Gaslini 5, I-16147 Genoa, Italy. RI Bosco, Maria Carla/J-7928-2016; varesio, luigi/J-8261-2016 OI Bosco, Maria Carla/0000-0003-1857-7193; varesio, luigi/0000-0001-5659-2218 NR 34 TC 4 Z9 4 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0969-7128 J9 GENE THER JI Gene Ther. PD MAR PY 2004 VL 11 IS 6 BP 560 EP 568 DI 10.1038/sj.gt.3302217 PG 9 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 780PU UT WOS:000189391200008 PM 14961065 ER PT J AU Hu, N Wang, CY Su, H Li, WJ Emmert-Buck, MR Li, G Roth, MJ Tang, ZZ Lu, N Giffen, C Albert, PS Taylor, PR Goldstein, AM AF Hu, N Wang, CY Su, H Li, WJ Emmert-Buck, MR Li, G Roth, MJ Tang, ZZ Lu, N Giffen, C Albert, PS Taylor, PR Goldstein, AM TI High frequency of CDKN2A alterations in esophageal squamous cell carcinoma from a high-risk Chinese population SO GENES CHROMOSOMES & CANCER LA English DT Article ID TUMOR-SUPPRESSOR GENE; HIGH-INCIDENCE AREA; ALLELIC LOSS; HOMOZYGOUS DELETION; FAMILY-HISTORY; CANCER; MUTATIONS; P16; METHYLATION; P16(INK4A) AB dBecause previous studies have shown that loss of heterozygosity (LOH) is common on chromosome arm 9p in esophageal squamous cell carcinoma (ESCC) and that genetic alterations in CDKN2A and CDKN2B on 9p are also common, we sought to determine whether LOH and these genetic alterations are related. We performed LOH studies on chromosome bands 9p21-p22 and searched for genetic alterations of CDKN2A and CDKN2B in 56 ESCCs from a high-risk Chinese population. Seventy-three percent of patients were found to have LOH at one or more loci on chromosome bands 9p21-p22, and LOH occurred more frequently in patients with a family history of upper gastrointestinal cancer than in those with a negative family history (P = 0.01, global permutation test). CDKN2A mutations (point mutations, deletions, insertions) were observed in 25% (14 of 56) of cases, and the LOH pattern was significantly different for individuals with and without a CDKN2A mutation (P = 0.01, global test). Three new single nucleotide polymorphisms (SNPs) and 2 previously reported SNPs were identified in this group of patients. Intragenic allelic loss at polymorphic sites in CDKN2A was detected in 32% (18 of 56) of patients. Seven of the 56 (13%) cases exhibited what is considered classic evidence (n = 4) or showed potential evidence (n = 3) of biallelic inactivation. Only one alteration was observed in CDKN2B, G171A in the 5' untranslated region. Both mutation and intragenic allelic loss in CDKN2A appear to play a role in the development of ESCC. (C) 2003 Wiley-Liss, Inc. (C) 2003 Wiley-Liss, Inc. C1 NCI, Canc Prevent Studies Branch, Canc Res Ctr, Bethesda, MD 20892 USA. Natl Vaccine & Serum Inst, Beijing, Peoples R China. Shanxi Canc Hosp, Shanxi, Peoples R China. Chinese Acad Med Sci, Canc Inst & Hosp, Beijing 100037, Peoples R China. Informat Management Serv Inc, Silver Spring, MD USA. NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Taylor, PR (reprint author), NCI, Canc Prevent Studies Branch, Canc Res Ctr, 6116 Execut Blvd,Room 705, Bethesda, MD 20892 USA. EM ptaylor@mail.nih.gov; goldstea@mail.nih.gov NR 41 TC 18 Z9 23 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 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD MAR PY 2004 VL 39 IS 3 BP 205 EP 216 DI 10.1002/gcc.10315 PG 12 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 772AN UT WOS:000188818300004 PM 14732922 ER PT J AU Wickner, RB Edskes, HK Roberts, BT Baxa, U Pierce, MM Ross, ED Brachmann, A AF Wickner, RB Edskes, HK Roberts, BT Baxa, U Pierce, MM Ross, ED Brachmann, A TI Prions: proteins as genes and infectious entities SO GENES & DEVELOPMENT LA English DT Review ID YEAST SACCHAROMYCES-CEREVISIAE; FUNGUS PODOSPORA-ANSERINA; CREUTZFELDT-JAKOB-DISEASE; TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES; CHAIN RELEASE FACTOR; DE-NOVO APPEARANCE; PSI+ PRION; GUANIDINE-HYDROCHLORIDE; SCRAPIE AGENT; SUP35 PROTEIN C1 NIDDKD, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. RP Wickner, RB (reprint author), NIDDKD, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. EM wickner@helix.nih.gov RI Brachmann, Andreas/I-2241-2013; OI Brachmann, Andreas/0000-0001-7980-8173; Ross, Eric/0000-0002-6473-9977 NR 147 TC 54 Z9 55 U1 0 U2 9 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD MAR 1 PY 2004 VL 18 IS 5 BP 470 EP 485 DI 10.1101/gad.1177104 PG 16 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 806BR UT WOS:000220409900002 PM 15037545 ER PT J AU Malagon, F Tong, AH Shafer, BK Strathern, JN AF Malagon, F Tong, AH Shafer, BK Strathern, JN TI Genetic interactions of DST1 in Saccharomyces cerevisiae suggest a role of TFIIS in the initiation-elongation transition SO GENETICS LA English DT Review ID RNA-POLYMERASE-II; FACILITATED TRANSCRIPT CLEAVAGE; PROTEIN PHOSPHATASE 2A; EXPRESSION IN-VIVO; YEAST HRS1 GENE; MESSENGER-RNA; MEDIATOR COMPLEX; FACTOR-SII; C-MYC; FUNCTIONAL-ORGANIZATION AB THIS promotes the intrinsic ability of RNA polymerase 11 to cleave the T-end of the newly synthesized RNA. This stimulatory activity of TFIIS, which is dependent upon Rpb9, facilitates the resumption of transcription elongation when the polymerase stalls or arrests. While THIS has a pronounced effect on transcription elongation in vitro, the deletion of DST1 has no major effect on cell viability. In this work we used a genetic approach to increase our knowledge of the role of TFIIS in vivo. We showed that: (1) dst1 and rpb9 mutants have a synthetic growth defective phenotype when combined with fyv4, gim5, htz1, yal011w, ybr231c, soh1, vps71, and vps72 mutants that is exacerbated during germination or at high salt concentrations; (2) TFIIS and Rpb9 are essential when the cells are challenged with microtubule-destabilizing drugs; (3) among the SDO (synthetic with Dst one), SOH1 shows the strongest genetic interaction with DST1; (4) the presence of multiple copies of TAF14, SUA7, GAL11, RTS1, and TYS1 alleviate the growth phenotype of dst1 soh1 mutants; and (5) SRB5 and SIN4 genetically interact with DST1. We propose that THIS is required under stress conditions and that TFIIS is important for the transition between initiation and elongation in vivo. C1 NCI, Gene Regulat & Chromosome Biol Lab, Frederick, MD 21702 USA. Univ Toronto, Banting & Best Dept Med Res, Toronto, ON M5G 1L6, Canada. Univ Toronto, Dept Med Genet & Microbiol, Toronto, ON M5S 1A8, Canada. RP NCI, Gene Regulat & Chromosome Biol Lab, Bldg 539,Rm 151,POB B, Frederick, MD 21702 USA. EM strather@ncifcrf.gov RI Malagon, Francisco/A-7059-2013 NR 157 TC 38 Z9 38 U1 1 U2 6 PU GENETICS SOCIETY AMERICA PI BETHESDA PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA SN 0016-6731 EI 1943-2631 J9 GENETICS JI Genetics PD MAR PY 2004 VL 166 IS 3 BP 1215 EP 1227 DI 10.1534/genetics.166.3.1215 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA 814BL UT WOS:000220950100010 PM 15082542 ER PT J AU Matsuzaki, H Loi, H Dong, S Tsai, YY Fang, J Law, J Di, XJ Liu, WM Yang, G Liu, GY Huang, J Kennedy, GC Ryder, TB Marcus, GA Walsh, PS Shriver, MD Puck, JM Jones, KW Mei, R AF Matsuzaki, H Loi, H Dong, S Tsai, YY Fang, J Law, J Di, XJ Liu, WM Yang, G Liu, GY Huang, J Kennedy, GC Ryder, TB Marcus, GA Walsh, PS Shriver, MD Puck, JM Jones, KW Mei, R TI Parallel genotyping of over 10,000 SNPs using a one-primer assay on a high-density oligonucleotide array SO GENOME RESEARCH LA English DT Article ID SINGLE-NUCLEOTIDE POLYMORPHISMS; HUMAN GENOME; LINKAGE ANALYSIS; DISEASE; MAP; DNA; IDENTIFICATION; MICROARRAYS AB The analysis of single nucleotide polymorphisms (SNPs) is increasingly utilized to investigate the genetic causes of complex human diseases. Here we present a high-throughout genotyping platform that uses a one-primer assay to genotype over 10,000 SNPs per individual oil a single oligonucleotide array. This approach uses restriction digestion to fractionate the genome, followed by amplification of a specific fractionated Subset of the genome. The resulting reduction in genome complexity enables allele-specific hybridization to the array. The selection of SNPs was primarily determined by computer-predicted lengths of restriction fragments containing the SNPs, and Was further driven by strict empirical measurements Of accuracy, reproducibility, and average call rate, which we estimate to be >9.5%, >99.9%, and >95%, respectively. With average heterozygosity of 0.38 and genome scan resolution of 0.31 cM, the SNP array is a viable alternative to panels of rnicrosatellites (STRs). As a demonstration of the utility of the genotyping platform in whole-genome scans, we have replicated and refined a linkage region on chromosome 2p for chronic mucocutaneous candidiasis and thyroid disease, previously identified using a panel of microsatellite (STR) markers. C1 Affymetrix Inc, Santa Clara, CA 95051 USA. Johns Hopkins Univ, Sch Med, CIDR, Baltimore, MD 21224 USA. Penn State Univ, Dept Anthropol, University Pk, PA 16802 USA. Natl Human Genome Inst, Genet & Mol Biol Branch, Bethesda, MD 20892 USA. RP Mei, R (reprint author), Affymetrix Inc, Santa Clara, CA 95051 USA. EM rui_mei@affymetrix.com NR 30 TC 202 Z9 215 U1 0 U2 9 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD MAR PY 2004 VL 14 IS 3 BP 414 EP 425 DI 10.1101/gr.2014904 PG 12 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 780PB UT WOS:000189389100010 PM 14993208 ER PT J AU Wang, ZN Fan, HT Yang, HH Hu, Y Buetow, KH Lee, MP AF Wang, ZN Fan, HT Yang, HH Hu, Y Buetow, KH Lee, MP TI Comparative sequence analysis of imprinted genes between human and mouse to reveal imprinting signatures SO GENOMICS LA English DT Article DE imprinting; motif; comparative genomics; logistic regression model ID BECKWITH-WIEDEMANN-SYNDROME; GENOMIC DNA; CPG ISLAND; REGION; DOMAIN; 11P15; RELAXATION; ELEMENTS; CANCER; LOCUS AB We performed a comparative genomic sequence analysis between human and mouse for 24 imprinted genes on human chromosomes 1, 6, 7, 11, 13, 14, 15, 18, 19, and 20. The MEME program was used to search for motifs within conserved sequences among the imprinted genes and we then used the MAST program to analyze for the presence or absence of motifs in the imprinted genes and 128 nonimprinted genes. Our analysis identified 15 motifs that were significantly enriched in the imprinted genes. We generated a logistic regression model by combining multiple motifs as input variables and the 24 imprinted genes and the 128 nonimprinted genes as a training set. The accuracy, sensitivity, and specificity of our model were 98, 92, and 99%, respectively. The model was further validated by an open test on 12 additional imprinted genes. The motifs identified in this study are novel imprinting signatures, which should improve our understanding of genomic imprinting and the role of genomic imprinting in human diseases. Published by Elsevier Inc. C1 NCI, Lab Populat Genet, Bethesda, MD 20892 USA. RP Lee, MP (reprint author), NCI, Lab Populat Genet, 41 Lib Dr,Room D702C, Bethesda, MD 20892 USA. EM leemax@mail.nih.gov NR 21 TC 18 Z9 19 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD MAR PY 2004 VL 83 IS 3 BP 395 EP 401 DI 10.1016/j.ygeno.2003.09.007 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 776CA UT WOS:000189096400006 PM 14962665 ER PT J AU Semba, RD Guralnik, JM Chaves, P Ricks, MO Fried, LP AF Semba, RD Guralnik, JM Chaves, P Ricks, MO Fried, LP TI Iron status and anemia in a population-based study of women with and without disability living in the community: the Women's Health and Aging Studies SO HAEMATOLOGICA LA English DT Letter DE aging; women; community; iron status; anemia ID DEFICIENCY; PREVALENCE AB Iron status and associated risk factors were assessed in a population-based study of 684 community-dwelling women, 70-79 years old. Iron deficiency, iron deficiency anemia, and elevated iron stores were found in 5.8%, 3.8%, and 9.0% of women, respectively. The prevalence of both anemia and iron deficiency anemia increased significantly with increasing disability. C1 Johns Hopkins Med Inst, Baltimore, MD 21205 USA. NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. Univ Estado Rio De Janeiro, Ctr Studies Aging & Care Elderly, Rio De Janeiro, Brazil. RP Semba, RD (reprint author), 550 N Broadway,Suite 700, Baltimore, MD 21205 USA. EM rdsembo@jhmi.edu FU NCRR NIH HHS [RR00722]; NIA NIH HHS [N01-AG12112., R01 AG11703-01A1]; NIAID NIH HHS [R01 AI41956] NR 10 TC 6 Z9 6 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOLOGICA JI Haematologica PD MAR PY 2004 VL 89 IS 3 BP 357 EP 358 PG 2 WC Hematology SC Hematology GA 801VT UT WOS:000220124100018 PM 15020276 ER PT J AU Belsky, J Booth, CL Bradley, R Burchinal, M Campbell, SB Clarke-Stewart, KA Cox, M Friedman, SL Hirsh-Pasek, K Huston, A Knoke, B Marshall, N McCartney, K O'Brien, M Owen, MT Payne, C Pianta, R Spieker, S Vandell, DL Weinraub, M AF Belsky, J Booth, CL Bradley, R Burchinal, M Campbell, SB Clarke-Stewart, KA Cox, M Friedman, SL Hirsh-Pasek, K Huston, A Knoke, B Marshall, N McCartney, K O'Brien, M Owen, MT Payne, C Pianta, R Spieker, S Vandell, DL Weinraub, M CA NICHD Early Child Care Res Network TI Multiple pathways to early academic achievement SO HARVARD EDUCATIONAL REVIEW LA English DT Article ID AMERICAN CHILDREN; PRESCHOOL; SCHOOL; CONSEQUENCES; INSTRUCTION; COMPETENCE; EDUCATION; BEHAVIOR; JAPANESE; CHINESE AB Using data from the National Institute of Child Health and Human Development (NICHD) Study of Early Child Care and Youth Development, the NICHD Early Child Care Research Network (ECCRN) constructed a structural model predicting reading and mathematics achievement in first-grade children from parenting, childcare, and first-grade schooling environments, which is presented in this article. The model provided a strong fit for the data, and parenting emerged as the strongest single contextual predictor of children's achievement. Nevertheless, the child-care and first-grade schooling contexts independently contributed to children's academic performance. There were also a number of indirect pathways of prediction that combined environmental and child factors. Overall, results confirmed that multiple factors act in concert over the school transition period to shape children's reading and mathematics skills. C1 NICHD, Early Child Care Res Network, CRMC, Rockville, MD 20852 USA. Univ London, London WC1E 7HU, England. Univ Washington, Seattle, WA 98195 USA. Univ Arkansas, Little Rock, AR 72204 USA. Univ N Carolina, Chapel Hill, NC USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. Univ Calif Irvine, Irvine, CA USA. Temple Univ, Philadelphia, PA 19122 USA. Univ Texas, Austin, TX 78712 USA. Res Triangle Inst, Res Triangle Pk, NC 27709 USA. Wellesley Coll, Wellesley, MA 02181 USA. Harvard Univ, Cambridge, MA 02138 USA. Univ N Carolina, Greensboro, NC 27412 USA. Univ Texas, Dallas, TX 75230 USA. Univ Virginia, Charlottesville, VA 22903 USA. Univ Wisconsin, Madison, WI USA. RP Belsky, J (reprint author), NICHD, Early Child Care Res Network, CRMC, 6100 Execut Blvd,4B05, Rockville, MD 20852 USA. RI Marshall, Nancy/C-3428-2012 NR 66 TC 55 Z9 55 U1 5 U2 17 PU HARVARD GRADUATE SCHOOL EDUCATION PI CAMBRIDGE PA HARVARD UNIV GUTMAN LIBRARY, STE 349, 6 APPIAN WAY, CAMBRIDGE, MA 02138 USA SN 0017-8055 J9 HARVARD EDUC REV JI Harv. Educ. Rev. PD SPR PY 2004 VL 74 IS 1 BP 1 EP 29 PG 29 WC Education & Educational Research SC Education & Educational Research GA 812PV UT WOS:000220852300001 ER PT J AU Wynn, TA Hesse, M Sandler, NG Kaviratne, M Hoffmann, KF Chiaramonte, MG Reiman, R Cheever, AW Sypek, JP Mentink-Kanel, MM AF Wynn, TA Hesse, M Sandler, NG Kaviratne, M Hoffmann, KF Chiaramonte, MG Reiman, R Cheever, AW Sypek, JP Mentink-Kanel, MM TI P-selectin suppresses hepatic inflammation and fibrosis in mice by regulating interferon gamma and the IL-13 decoy receptor SO HEPATOLOGY LA English DT Article ID PULMONARY GRANULOMA-FORMATION; SCHISTOSOMA-MANSONI; MURINE SCHISTOSOMIASIS; EOSINOPHIL RECRUITMENT; AIRWAY INFLAMMATION; ENDOTHELIAL-CELLS; T-HELPER-2 CELLS; IMMUNE-RESPONSE; DEFICIENT MICE; TH2 CELLS AB The selectin family of cell adhesion molecules is widely thought to promote inflammatory reactions by facilitating leukocyte recruitment. However, it was unexpectedly found that mice with targeted deletion of the P-selectin gene (PsKO mice) developed unpolarized type 1/type 2 cytokine responses and severely aggravated liver pathology following infection with the type 2-promoting pathogen Schistosoma mansoni. In fact, liver fibrosis, which is dependent on interleukin 13 (IL-13), increased by a factor of more than 6, despite simultaneous induction of the antifibrotic cytokine interferon gamma (IFN-gamma). Inflammation, as measured by granuloma size, also increased significantly in the absence of P-selectin. When infected PsKO mice were treated with neutralizing anti-IFN-gamma monoclonal antibodies, however, granuloma size was restored to wild-type levels; this finding revealed the potent proinflammatory role of IFN-gamma when expressed concomitantly with IL-13. Untreated PsKO mice also exhibited a significant (sixfold) reduction in decoy IL-13 receptor (IL-13 receptor alpha-2) expression when compared with infected wild-type animals. It is noteworthy, however, that when decoy receptor activity was restored in PsKO mice by treatment with soluble IL-13 receptor alpha-2-Fc, the exacerbated fibrotic response was completely inhibited. Thus, reduced expression of the decoy IL-13 receptor mediated by the elevated type 1 cytokine response probably accounts for the enhanced activity of IL-13 in PsKO mice and for the resultant increase in collagen deposition. In conclusion, the current study has revealed the critical role of P-selectin in the progression of chronic liver disease caused by schistosome parasites. By suppressing IFN-gamma and up-regulating the decoy IL-13 receptor, P-selectin dramatically inhibits the pathologic tissue remodeling that results from chronic type 2 cytokine-mediated inflammation. C1 NIAID, Immunopathogenesis Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Biomed Res Inst, Rockville, MD 20852 USA. Wyeth Res, Cambridge, MA USA. RP Wynn, TA (reprint author), NIAID, Immunopathogenesis Sect, Parasit Dis Lab, NIH, Bldg 50,Rm 6154,MSC 8003, Bethesda, MD 20892 USA. EM tuynn@niaid.nih.gov RI Wynn, Thomas/C-2797-2011; OI Utay, Netanya/0000-0002-6407-8670 NR 50 TC 23 Z9 25 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD MAR PY 2004 VL 39 IS 3 BP 676 EP 687 DI 10.1002/hep.20102 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 806IP UT WOS:000220427900014 PM 14999686 ER PT J AU Shenoy, G Kim, P Goodwin, M Nguyen, QA Barry, CE Dowd, CS AF Shenoy, G Kim, P Goodwin, M Nguyen, QA Barry, CE Dowd, CS TI Synthesis and spectroscopic differentiation of 2-and 4-alkoxythiotetronic acids SO HETEROCYCLES LA English DT Article ID TETRONIC ACIDS; MARINE SPONGE; THIOLACTOMYCIN; SESTERTERPENE; ETHERS AB O-Alkylation of thiotetronic acids gives a mixture of 2- and 4-position enol ether products. Comparison of the physical data revealed that UV spectroscopy was the most reliable method of distinguishing between these related ethers. We have determined that 4-position ethers have a distinct absorption between 235-240 rim, while 2-position ethers have two absorbance peaks, one between 205-220 rim and the other between 305-310 nm. This report describes the synthesis and unambiguous characterization of 2- and 4-methoxy-3,5-dimethylthiotetronic acids. The UV absorption properties of several other pairs of thiotetronic acid ethers confirm that these differences are general features that provide a simple method for distinguishing between 2- and 4-substituted isomers. C1 NIAID, TB Res Sect, Rockville, MD 20852 USA. RP Shenoy, G (reprint author), NIAID, TB Res Sect, Rockville, MD 20852 USA. EM cdowd@niaid.nih.gov RI Barry, III, Clifton/H-3839-2012 FU Intramural NIH HHS [Z01 AI000693-13] NR 20 TC 15 Z9 15 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 MAR 1 PY 2004 VL 63 IS 3 BP 519 EP 527 PG 9 WC Chemistry, Organic SC Chemistry GA 779XL UT WOS:000189327400003 PM 16733529 ER PT J AU Belyakov, IM Berzofsky, JA AF Belyakov, IM Berzofsky, JA TI Immunobiology of mucosal HIV infection and the basis for development of a new generation of mucosal AIDS vaccines SO IMMUNITY LA English DT Review ID SIMIAN IMMUNODEFICIENCY VIRUS; CYTOTOXIC T-LYMPHOCYTES; LYMPH-NODE IMMUNIZATION; CHEMOKINE RECEPTOR 9; DENDRITIC CELLS; PEYERS PATCH; IMMUNE-RESPONSES; RHESUS MACAQUES; SIV INFECTION; CPG MOTIFS AB Mucosal tissues are the primary site of natural HIV transmission and a major reservoir for HIV replication. Targeting immune responses to the mucosal entry site before viral dissemination could protect and also clear viral reservoirs. Recent understanding of mucosal HIV transmission and of chemokines and integrins in mucosal trafficking can aid design of new strategies to enhance AIDS vaccine efficacy. C1 NCI, Vaccine Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Belyakov, IM (reprint author), NCI, Vaccine Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM belyakov@mail.nih.gov NR 53 TC 97 Z9 106 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD MAR PY 2004 VL 20 IS 3 BP 247 EP 253 DI 10.1016/S1074-7613(04)00053-6 PG 7 WC Immunology SC Immunology GA 821EJ UT WOS:000221442600003 PM 15030769 ER PT J AU Dittmer, U He, H Messer, RJ Schimmer, S Olbrich, ARM Ohlen, C Greenberg, PD Stromnes, IM Iwashiro, M Sakaguchi, S Evans, LH Peterson, KE Yang, GJ Hasenkrug, KJ AF Dittmer, U He, H Messer, RJ Schimmer, S Olbrich, ARM Ohlen, C Greenberg, PD Stromnes, IM Iwashiro, M Sakaguchi, S Evans, LH Peterson, KE Yang, GJ Hasenkrug, KJ TI Functional impairment of CD8(+) T cells by regulatory T cells during persistent retroviral infection SO IMMUNITY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; HEPATITIS-C VIRUS; GAMMA-INTERFERON; FRIEND-VIRUS; PERFORIN EXPRESSION; DISEASE PROGRESSION; EFFECTOR FUNCTION; LEISHMANIA-MAJOR; HIV-1 INFECTION; HELPER TYPE-1 AB The establishment of viral persistence generally requires evasion of the host CD8(+) T cell response. Here we describe a form of evasion wherein the CD8(+) T cells are fully capable of recognizing their cognate antigen but their effector functions are suppressed by regulatory T cells. Virus-specific CD8(+) T cells adoptively transferred into mice persistently infected with Friend virus proliferated and appeared activated, but failed to produce IFNgamma or reduce virus loads. Cotransfer experiments revealed that a subpopulation of CD4(+) T cells from persistently infected mice suppressed IFNgamma production by the CD8(+) T cells. Treatment of persistently infected mice with anti-GITR antibody to ameliorate suppression by regulatory T cells significantly improved IFNgamma production by transferred CD8(+) T cells and allowed a significant reduction in viral loads. The results indicate that CD4(+) regulatory T cells contribute to viral persistence and demonstrate an immunotherapy for treating chronic retroviral infections. C1 NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, Natl Inst Hlth, Hamilton, MT 59840 USA. Univ Klinikum Essen, Inst Virol, D-45122 Essen, Germany. Univ Washington, Dept Med & Immunol, Seattle, WA 98195 USA. Kyoto Univ, Dept Expt Pathol, Inst Frontier Med Sci, Kyoto 6068507, Japan. RP Hasenkrug, KJ (reprint author), NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, Natl Inst Hlth, Hamilton, MT 59840 USA. EM khasenkrug@nih.gov RI Sakaguchi, Shimon/C-9535-2009; Peterson, Karin/D-1492-2016 OI Peterson, Karin/0000-0003-4177-7249 NR 52 TC 232 Z9 243 U1 1 U2 4 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD MAR PY 2004 VL 20 IS 3 BP 293 EP 303 DI 10.1016/S1074-7613(04)00054-8 PG 11 WC Immunology SC Immunology GA 821EJ UT WOS:000221442600007 PM 15030773 ER PT J AU Costa, DJ Favali, C Clarencio, J Afonso, L Conceicao, V Miranda, JC Titus, RG Valenzuela, J Barral-Netto, M Barral, A Brodskyn, CI AF Costa, DJ Favali, C Clarencio, J Afonso, L Conceicao, V Miranda, JC Titus, RG Valenzuela, J Barral-Netto, M Barral, A Brodskyn, CI TI Lutzomyia longipalpis salivary gland homogenate impairs cytokine production and costimulatory molecule expression on human monocytes and dendritic cells SO INFECTION AND IMMUNITY LA English DT Article ID TUMOR-NECROSIS-FACTOR; SAND FLY SALIVA; LEISHMANIA-MAJOR INFECTION; EXPERIMENTAL CUTANEOUS LEISHMANIASIS; DELAYED-TYPE HYPERSENSITIVITY; PROTEIN PHOSPHATASE-ACTIVITY; NITRIC-OXIDE PRODUCTION; VECTOR SALIVA; FACTOR-ALPHA; TNF-ALPHA AB In this report, we describe an investigation of the effects of Lutzomyia longipalpis sand fly salivary gland homogenates (SGH) on cytokine production and expression of costimulatory molecules on human monocytes, macrophages (Mphis), and dendritic cells (DCs). SGH of L. longipalpis induced an increase in interleukin-6 (IL-6), IL-8 and IL-12p40 production but a decrease in tumor necrosis factor alpha and IL-10 production by lipopolysaccharida (LPS)-stimulated monocytes. We also examined the expression of costimulatory molecules on the surface of monocytes, Mphis, and DCs. Whereas SGH affected the expression of these molecules on monocytes and Mphis, it had little effect on these molecules on DCs. However, when DCs were generated from human monocytes in the presence of SGH, SGH inhibited the expression of costimulatory molecules. In addition, a decrease in the maturation of DCs induced by CD40L was observed in the presence of SGH. Finally, preincubating SGH with human sera containing anti-SGH-specific antibodies abolished the effects of SGH on cytokine production by LPS-stimulated monocytes. C1 Ctr Pesquisa Goncalo Moniz, FIOCRUZ, Lab Imunoparasitol, BR-40295001 Salvador, BA, Brazil. Univ Fed Bahia, Inst Ciencias Saude, Salvador, BA, Brazil. Univ Fed Bahia, Fac Med, Salvador, BA, Brazil. Immunol Invest Inst Salvador, Salvador, BA, Brazil. Colorado State Univ, Coll Vet Med & Biomed Sci, Dept Microbiol Immunol & Pathol, Ft Collins, CO 80523 USA. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Brodskyn, CI (reprint author), Ctr Pesquisa Goncalo Moniz, FIOCRUZ, Lab Imunoparasitol, Rua Waldemar Falcao 121, BR-40295001 Salvador, BA, Brazil. EM brodskyn@cpqgm.fiocruz.br RI Barral Netto, Manoel/B-3904-2009; Barral, Aldina/B-4191-2009; Favali, Cecilia/C-1028-2009; Brodskyn, Claudia/A-9970-2010; Clarencio, Jorge/H-3940-2012 OI Barral Netto, Manoel/0000-0002-5823-7903; Barral, Aldina/0000-0002-7177-464X; FU NIAID NIH HHS [AI30639, P50 AI030639] NR 45 TC 29 Z9 29 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 MAR PY 2004 VL 72 IS 3 BP 1298 EP 1305 DI 10.1128/IAI.72.3.1298-1305.2004 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 778ZH UT WOS:000189270800010 PM 14977931 ER PT J AU Zuckert, WR Lloyd, JE Stewart, PE Rosa, PA Barbour, AG AF Zuckert, WR Lloyd, JE Stewart, PE Rosa, PA Barbour, AG TI Cross-species surface display of functional spirochetal lipoproteins by recombinant Borrelia burgdorferi SO INFECTION AND IMMUNITY LA English DT Article ID LYME-DISEASE SPIROCHETE; CRYSTAL-STRUCTURE; RELAPSING FEVER; ESCHERICHIA-COLI; PROTEIN-A; CIRCULAR PLASMID; IN-VITRO; HERMSII; SEQUENCE; MICE AB Surface-exposed lipoproteins of relapsing fever (RF) and Lyme borreliosis Borrelia spirochetes mediate certain interactions of the bacteria with their arthropod and vertebrate hosts. RF spirochetes such as Borrelia hermsii serially evade the host's antibody response by multiphasic antigenic variation of Vsp and Vlp proteins. Furthermore, the expression of Vsp1 and Vsp2 by Borrelia turicatae is associated with neurotropism and higher blood densities, respectively. In contrast to RF Borrelia species, the Lyme borreliosis spirochete Borrelia burgdorferi is amenable to genetic manipulation. To facilitate structure-function analyses of RF surface lipoproteins, we used recombinant plasmids to introduce full-length vsp1 and vsp2 as well as two representative vlp genes into B. burgdorferi cells. Recombinant B. burgdorferi cells constitutively expressed the proteins under the control of the B. burgdorferi flaB promoter. Antibody and protease accessibility assays indicated proper surface exposure and folding. Expression of Vsp1 and Vsp2 conferred glycosaminoglycan binding to recombinant B. burgdorferi cells that was similar to that observed with purified recombinant proteins and B. turicatae expressing native Vsp. These data demonstrate that the lipoprotein modification and export mechanisms in the genus Borrelia are conserved. They also validate the use of recombinant B. burgdorferi in studies of surface lipoprotein structure-function and the biogenesis of spirochete membranes. C1 Univ Kansas, Med Ctr, Dept Microbiol Mol Genet & Immunol, Kansas City, KS 66160 USA. Univ Calif Irvine, Dept Microbiol & Mol Genet, Irvine, CA 92697 USA. Univ Calif Irvine, Dept Med, Irvine, CA 92697 USA. NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Zuckert, WR (reprint author), Univ Kansas, Med Ctr, Dept Microbiol Mol Genet & Immunol, 3025 Wahl Hall W,3901 Rainbow Blvd, Kansas City, KS 66160 USA. EM wzueckert@kumc.edu RI Barbour, Alan/B-3160-2009 OI Barbour, Alan/0000-0002-0719-5248 FU NCRR NIH HHS [P20 RR016443, RR16443]; NIAID NIH HHS [AI24424, R01 AI024424, R37 AI024424] NR 56 TC 25 Z9 25 U1 0 U2 1 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 MAR PY 2004 VL 72 IS 3 BP 1463 EP 1469 DI 10.1128/IAI.72.3.1463-1469.2004 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 778ZH UT WOS:000189270800030 PM 14977951 ER PT J AU Seshu, J Boylan, JA Gherardini, FC Skare, JT AF Seshu, J Boylan, JA Gherardini, FC Skare, JT TI Dissolved oxygen levels alter gene expression and antigen profiles in Borrelia burgdorferi SO INFECTION AND IMMUNITY LA English DT Article ID LYME-DISEASE SPIROCHETE; OXIDATIVE STRESS; MAMMALIAN HOST; TRANSCRIPTIONAL ACTIVATOR; RESPONSE REGULATOR; ANIMAL-MODEL; PROTEIN; DNA; ADAPTATION; INFECTION AB The Lyme disease spirochete, Borrelia burgdorferi, encounters many environmental signals as it cycles between the arthropod vector and mammalian hosts, including temperature, pH, and other host factors. To test the possibility that dissolved oxygen modulates gene expression in B. burgdorferi, spirochetes were exposed to differential levels of dissolved oxygen, and distinct alterations were observed at both the transcriptional and translational levels. Specifically NapA, a Dps/Dpr homologue involved in the oxidative stress response in other bacteria, was reduced when B. burgdorferi was grown under oxygen-limiting conditions. In contrast, several immunoreactive proteins were altered when tested with infection-derived sera from different hosts. Specifically, OspC, DbpA, and VlsE were synthesized at greater levels when cells were grown in limiting oxygen, whereas VraA was reduced. The levels of oxygen in the medium did not affect OspA production. Real-time reverse transcription-PCR analysis of RNA isolated from infectious isolates of strains B31 and cN40 indicated that the expression of ospC, dbpA, and vlsE increased while napA expression decreased under dissolved-oxygen-limiting conditions, whereas flaB was not affected. The reverse transcription-PCR results corroborated the immunoblot analyses and indicated that the increase in OspC, DbpA, and VlsE was due to regulation at the transcriptional level of the genes encoding these antigens. These results indicate that dissolved oxygen modulates gene expression in B. burgdorferi and imply that the redox environment may be an additional regulatory cue that spirochetes exploit to adapt to the disparate niches that they occupy in nature. C1 Texas A&M Univ, Syst Hlth Sci Ctr, Dept Med Microbiol & Immunol, College Stn, TX 77843 USA. NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, Hamilton, MT 59840 USA. RP Skare, JT (reprint author), Texas A&M Univ, Syst Hlth Sci Ctr, Dept Med Microbiol & Immunol, 407 Reynolds Med Bldg, College Stn, TX 77843 USA. EM jskare@tamu.edu FU NIAID NIH HHS [AI-42345, R01 AI042345] NR 40 TC 54 Z9 54 U1 1 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 MAR PY 2004 VL 72 IS 3 BP 1580 EP 1586 DI 10.1128/IAI.72.3.1580-1586.2004 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 778ZH UT WOS:000189270800043 PM 14977964 ER PT J AU Taylor, DW Zhou, A Marsillio, LE Thuita, LW Leke, EB Branch, O Gowda, DC Long, C Leke, RFG AF Taylor, DW Zhou, A Marsillio, LE Thuita, LW Leke, EB Branch, O Gowda, DC Long, C Leke, RFG TI Antibodies that inhibit binding of Plasmodium falciparum-infected erythrocytes to chondroitin sulfate A and to the C terminus of merozoite surface protein 1 correlate with reduced placental malaria in cameroonian women SO INFECTION AND IMMUNITY LA English DT Article ID BLOOD-STAGE ANTIGENS; PREGNANT-WOMEN; CIRCUMSPOROZOITE PROTEIN; PARASITE ADHESION; ADHERENCE; RESPONSES; IDENTIFICATION; PROTEOGLYCANS; MALAWI AB Plasmodium falciparum-infected erythrocytes often sequester in the placenta of pregnant women, producing placental malaria, a condition that can compromise the health of the developing fetus. Scientists are hopeful that a vaccine can be developed to prevent this condition. Immunological mechanisms responsible for eliminating parasites from the placenta remain unclear, but antibodies to the carboxyl-terminal 19-kDa segment of the merozoite surface protein 1 (MSP1-19), the ring-infected erythrocyte surface antigen (RESA), and an erythrocyte-surface ligand that binds chondroitin sulfate A (CSA-L) have been implicated. In addition, antibodies to sporozoite and liver-stage antigens could reduce initial parasite burdens. This study sought to determine if antibodies to the circumsporozoite protein (CSP), liver-stage antigen 1 (LSA1), RESA, MSP1-19, or CSA-L correlated with either the absence of placental parasites or low placental parasitemias. Using a frequency-matched case-control study design, we compared antibody levels in women (gravidity 1 to 11) with and without placental malaria. Results showed that women who were antibody negative for MSP1-19 were at a higher risk of having placental malaria than women with antibodies (P < 0.007). Furthermore, an association between high levels of antibodies that blocked the binding of infected erythrocytes to CSA and low placental parasitemias was observed (P = 0.02). On the other hand, women with high antibody levels at term to CSP, LSA1, and RESA were more likely to have placental malaria than antibody-negative women. Since antibodies to MSP1-19 and CSA-L were associated with reduced placental malaria, both antigens show promise for inclusion in a vaccine for women of child-bearing age. C1 Georgetown Univ, Dept Biol, Reiss Sci Ctr, Washington, DC 20057 USA. Univ Alabama, Dept Geog Med, Birmingham, AL USA. Penn State Univ, Coll Med, Dept Biochem & Mol Biol, Hershey, PA USA. Az Data Clin Inc, Rockville, MD USA. NIAID, Malaria Vaccine Dev Univ, NIH, Rockville, MD USA. Univ Yaounde 1, Ctr Biotechnol, Fac Med & Biomed Sci, Yaounde, Cameroon. RP Taylor, DW (reprint author), Georgetown Univ, Dept Biol, Reiss Sci Ctr, Room 406,37th & O St,NW, Washington, DC 20057 USA. EM taylordw@georgetown.edu FU NIAID NIH HHS [AI-45086, R01 AI045086, R21 AI045086, U01 AI035839, U01 AI043888, UO1 AI 35839, UO1AI 43888] NR 25 TC 20 Z9 22 U1 0 U2 1 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 MAR PY 2004 VL 72 IS 3 BP 1603 EP 1607 DI 10.1128/IAI.72.3.1603-1607.2004 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 778ZH UT WOS:000189270800046 PM 14977967 ER PT J AU Reid, SD Montgomery, AG Musser, JM AF Reid, SD Montgomery, AG Musser, JM TI Identification of srv, a PrfA-like regulator of group a Streptococcus that influences virulence SO INFECTION AND IMMUNITY LA English DT Article ID LISTERIA-MONOCYTOGENES VIRULENCE; HUMAN SEROLOGIC RESPONSE; CRP-FNR FAMILY; PLEIOTROPIC ACTIVATOR; GENE-TRANSCRIPTION; TARGET SEQUENCES; RECEPTOR PROTEIN; EXPRESSION; PYOGENES; INACTIVATION AB We have identified a Crp/Fnr-like transcriptional regulator of Streptococcus pyogenes that when inactivated attenuates virulence. The gene, named srv for streptococcal regulator of virulence, encodes a 240-amino-acid protein with 53% amino acid similarity to PrfA, a transcriptional activator of virulence in Listeria monocytogenes. C1 NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Reid, SD (reprint author), Wake Forest Univ, Sch Med, Dept Microbiol & Immunol, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM sreid@wfubmc.edu NR 36 TC 18 Z9 18 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 MAR PY 2004 VL 72 IS 3 BP 1799 EP 1803 DI 10.1128/IAI.72.3.1799-1803.2004 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 778ZH UT WOS:000189270800069 PM 14977990 ER PT J AU Tramont, EC AF Tramont, EC TI The impact of syphilis on humankind SO INFECTIOUS DISEASE CLINICS OF NORTH AMERICA LA English DT Article AB Until the advent of penicillin and the antibiotic era in the mid-20th century, syphilis was a prevalent disease, infecting between 8% and 14% of the population living in urban areas. The disease progressed to a chronic illness in up to 25% of patients, and its late neurologic manifestations had a profound affect on Western history when it infected societal leaders; on societal morays as a means to curb the disease; and on public health practices. Syphilis was a major impetus for the advent of strict informed consent policies. C1 NIAID, Div AIDS, NIH, Bethesda, MD 20892 USA. RP Tramont, EC (reprint author), NIAID, Div AIDS, NIH, 6700B Rockledge Dr, Bethesda, MD 20892 USA. EM etramont@niaid.nih.gov NR 21 TC 3 Z9 4 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0891-5520 J9 INFECT DIS CLIN N AM JI Infect. Dis. Clin. North Am. PD MAR PY 2004 VL 18 IS 1 BP 101 EP + DI 10.1016/S0891-5520(03)00092-8 PG 11 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 816DK UT WOS:000221090400009 PM 15081507 ER PT J AU Gius, D Mattson, D Bradbury, CM Smart, DK Spitz, DR AF Gius, D Mattson, D Bradbury, CM Smart, DK Spitz, DR TI Thermal stress and the disruption of redox-sensitive signalling and transcription factor activation: possible role in radiosensitization SO INTERNATIONAL JOURNAL OF HYPERTHERMIA LA English DT Article DE hyperthermia; signalling; AP-1; NF-kappa B; redox regulation ID DNA-BINDING ACTIVITY; HEAT-SHOCK RESPONSE; NF-KAPPA-B; P38 MAP KINASE; CHINESE-HAMSTER FIBROBLASTS; NECROSIS-FACTOR-ALPHA; IMMEDIATE-EARLY GENES; SOFT-TISSUE SARCOMAS; OXIDATIVE STRESS; IONIZING-RADIATION AB In spite of ongoing research efforts, the specific mechanism(s) of heat-induced alterations in the cellular response to ionizing radiation (IR) remain ambiguous, in part because they likely involve multiple mechanisms and potential targets. One such group of potential targets includes a class of cytoplasmic signalling and/or nuclear transcription factors known as immediate early response genes, which have been suggested to perform cytotoxic as well as cytoprotective roles during cancer therapy. One established mechanism regulating the activity of these early response elements involves changes in cellular oxidation/reduction (redox) status. After establishing common alterations in early response genes by oxidative stress and heat exposure, one could infer that heat shock may have similarities to other forms of environmental antagonists that induce oxidative stress. In this review, recent evidence supporting a mechanistic link between heat shock and oxidative stress will be summarized. In addition, the hypothesis that one mechanism whereby heat shock alters cellular responses to anticancer agents (including hyperthermic radiosensitization) is through heat-induced disruption of redox-sensitive signalling factors will be discussed. C1 NCI, Mol Radiat Oncol Sect, Radiat Oncol Branch, Radiat Oncol Sci Program,Ctr Canc Res,NIH, Bethesda, MD 20892 USA. Univ Iowa, Dept Radiat Oncol, Free Rad & Radiat Biol Program, Med Labs B180, Iowa City, IA 52242 USA. RP Gius, D (reprint author), NCI, Mol Oncol Sect, Radiat Oncol Branch, Radiat Oncol Sci Program,Ctr Canc Res,NIH, Bldg 10,Room B3B69,9000 Rockville Pike, Bethesda, MD 20892 USA. EM giusd@mail.nih.gov FU NCI NIH HHS [P01CA66081]; NHLBI NIH HHS [R01HL51469] NR 98 TC 9 Z9 9 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0265-6736 J9 INT J HYPERTHER JI Int. J. Hyperthermia PD MAR PY 2004 VL 20 IS 2 BP 213 EP 223 DI 10.1080/02656730310001619505 PG 11 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 800ST UT WOS:000220048700011 PM 15195515 ER PT J AU Mattson, D Bradbury, CM Bisht, KS Curry, HA Spitz, DR Gius, D AF Mattson, D Bradbury, CM Bisht, KS Curry, HA Spitz, DR Gius, D TI Heat shock and the activation of AP-1 and inhibition of NF-kappa B DNA-binding activity: possible role of intracellular redox status SO INTERNATIONAL JOURNAL OF HYPERTHERMIA LA English DT Article DE thermal stress; signalling; AP-1; NF-kappa B ID RADIATION-INDUCED ACTIVATION; PROTEIN-KINASE ACTIVATION; CHINESE-HAMSTER CELLS; HUMAN TUMOR-CELLS; P38 MAP KINASE; IONIZING-RADIATION; OXIDATIVE STRESS; GLUCOSE DEPRIVATION; HYDROGEN-PEROXIDE; GENE-EXPRESSION AB The early response genes comprising the AP-1 and NF-kappaB transcription factors are induced by environmental stress and thought to modulate responses to injury processes through the induction of target genes. Exposure to heat and ionizing radiation (IR) has been shown to affect signalling machinery involved in AP-1 and NF-kappaB activation. Furthermore, regulation of the signalling pathways leading to the activation of these transcription factors has been linked to changes in intracellular oxidation/reduction (redox) reactions. The hypothesis is proposed that exposure to thermal stress and/or IR might alter metabolic processes impacting upon cellular redox state and thereby modify the activity of redox-sensitive transcription factors such as AP-1 and NF-kappaB. Gel electromobility shift assays (EMSA) demonstrated that heat shock-induced AP-1 DNA-binding activity but inhibited IR-induced activation of NF-kappaB. A time course showed that activation of the AP-1 complex occurs between 4 and 5 h following thermal stress, and inhibition of IR-induced NF-kappaB activation also occurs during this time interval. Using a redox-sensitive fluorescent probe [5-(and -6)-carboxy-2',7'-dichlorodihydrofluorescein diacetate], a shift to 40% less intracellular dye oxidation was observed in HeLa cells 0-4 h post-heat shock (45degreesC, 15 min) relative to cells held at 37degreesC. This was followed by a shift to greater dye oxidation between 4 and 12 h after treatment (about 1.8-fold) that returned to control levels by 24 h post-heating. These results show changes in DNA-binding activity closely paralleled apparent heat-induced changes in the intracellular redox state. Taken together, these results provide correlative evidence for disruption of redox-sensitive IR-induced signalling pathways by heat shock and support the hypothesis that this mechanism might play a role in heat-induced alterations in radiation response. C1 NCI, Sect Mol Radiat Oncol, Radiat Oncol Branch, Radiat Oncol Sci Program,Ctr Canc Res,NIH, Bethesda, MD 20892 USA. Univ Iowa, Dept Radiat Oncol, Free Rad & Radiat Biol Program, Med Labs B180, Iowa City, IA USA. Washington Univ, Dept Radiat Oncol, Div Radiat & Canc Biol, Sch Med,Mallinckrodt Inst Radiol, St Louis, MO 63108 USA. RP Gius, D (reprint author), NCI, Sect Mol Radiat Oncol, Radiat Oncol Branch, Radiat Oncol Sci Program,Ctr Canc Res,NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM giusd@mail.nih.gov FU NCI NIH HHS [1 K08 CA72602-01, P01 CA66081]; NHLBI NIH HHS [R01 HL51469] NR 46 TC 15 Z9 16 U1 0 U2 2 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0265-6736 J9 INT J HYPERTHER JI Int. J. Hyperthermia PD MAR PY 2004 VL 20 IS 2 BP 224 EP 233 DI 10.1080/02656730310001619956 PG 10 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 800ST UT WOS:000220048700012 PM 15195516 ER PT J AU Pradel, G Hayton, K Bonawitz, A Mejia, C Templeton, T AF Pradel, G Hayton, K Bonawitz, A Mejia, C Templeton, T TI A multi-domain adhesion protein family expressed in Plasmodium falciparum gametocytes is essential for sporozolite midgut to salivary gland transition SO INTERNATIONAL JOURNAL OF MEDICAL MICROBIOLOGY LA English DT Meeting Abstract CT 21st Congress of the German-Society-of-Parasitology CY MAR 17-20, 2004 CL Univ Wurzburg, Wurzburg, GERMANY SP German Soc Parasitol HO Univ Wurzburg C1 Cornell Univ, Weill Med Coll, Dept Microbiol & Immunol, Ithaca, NY 14853 USA. NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU URBAN & FISCHER VERLAG PI JENA PA BRANCH OFFICE JENA, P O BOX 100537, D-07705 JENA, GERMANY SN 1438-4221 J9 INT J MED MICROBIOL JI Int. J. Med. Microbiol. PD MAR PY 2004 VL 293 SU 38 BP 97 EP 97 PG 1 WC Microbiology; Virology SC Microbiology; Virology GA 836XQ UT WOS:000222589900142 ER PT J AU Dancey, J AF Dancey, J TI Epidermal growth factor receptor inhibitors in clinical development SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT Symposium on Epidermal Growth Factor Receptor Inhibitors and Cancer Therapeutics CY JUN 04, 2002 CL PHILADELPHIA, PENNSYLVANIA SP Radiat Therapy Oncol Grp, AstraZeneca Phamaceut, Bristrol-Meyers Squibb/Imclone Syst, Genentech, Novartis Oncol, Abgenix/Amgen, Wyeth Oncol DE epidermal growth factor receptor; inhibitors; review ID TYROSINE KINASE INHIBITOR; PHASE-I; MONOCLONAL-ANTIBODY; CANCER-THERAPY; ABX-EGF; ZD1839; CARCINOMAS; IRESSA; TRIAL; CELLS AB In cancer cells, aberrant signaling through the epidermal growth factor receptor (EGFR) activates pathways that stimulate many of the properties associated with neoplasia, including proliferation, migration, stromal invasion, tumor angiogenesis, and resistance to cell death-inducing signals. Because of the frequency of abnormalities in receptor signaling in human cancers, the EGFR is an attractive target for therapeutic development. Monoclonal antibodies and small molecule tyrosine kinase inhibitors are the two classes of agents that are the furthest advanced in clinical development. Although pharmacologic and mechanistic differences exist between the two classes, the results of preclinical studies suggest that both inhibit proliferation, have little normal tissue toxicity, and are additive/synergistic with standard therapies. The results from early clinical trials have indicated that both classes of agents are well tolerated and have antitumor activity. However, the first Phase III studies to be completed have not shown an improvement in survival with the addition of the monoclonal antibody C225 to cisplatin in patients with head-and-neck carcinoma or the addition of the kinase inhibitor ZD1839 to chemotherapy in patients with advanced lung cancer. Ongoing and future studies must address issues related to the selection of patients for study, dose and schedule of administration, monotherapy vs. combination treatment, and combinations with standard and investigational agents. (C) 2004 Elsevier Inc. C1 NCI, Invest Drug Branch, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. RP Dancey, J (reprint author), NCI, Invest Drug Branch, Canc Therapy Evaluat Program, Execut Plaza N,6130 Execut Blvd,Rm 7131, Bethesda, MD 20892 USA. EM danceyj@ctep.nci.nih.gov NR 40 TC 21 Z9 25 U1 1 U2 1 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. PD MAR 1 PY 2004 VL 58 IS 3 BP 1003 EP 1007 DI 10.1016/j.ijrobp.2003.07.011 PG 5 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 773QP UT WOS:000188934600046 PM 14967462 ER PT J AU El Sahly, HM Wright, JA Soini, H Bui, TT Williams-Bouyer, N Escalante, P Musser, JM Graviss, EA AF El Sahly, HM Wright, JA Soini, H Bui, TT Williams-Bouyer, N Escalante, P Musser, JM Graviss, EA TI Recurrent tuberculosis in Houston, Texas: a population-based study SO INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE LA English DT Article; Proceedings Paper CT 39th Annual Meeting of the Infectious-Diseases-Society-of-America CY OCT 25-28, 2001 CL SAN FRANCISCO, CA SP Infect Dis Soc Amer DE genotyping; molecular epidemiology; re-infection ID HUMAN-IMMUNODEFICIENCY-VIRUS; DRUG-RESISTANT TUBERCULOSIS; DIRECTLY OBSERVED THERAPY; MYCOBACTERIUM-TUBERCULOSIS; PULMONARY TUBERCULOSIS; EXOGENOUS REINFECTION; INFECTION; RELAPSE; DISEASE; TRIAL AB OBJECTIVE: To determine the predictors of recurrence of tuberculosis (TB), the drug resistance pattern of Mycobacterium tuberculosis strains recovered from recurrent TB patients, and the frequency of re-infection with a new M. tuberculosis strain among patients with recurrent disease. DESIGN: A population-based, retrospective case-control study using the Houston Tuberculosis Initiative database. RESULTS: We found that, among 100 patients with recurrent TB who completed adequate therapy for a first episode of TB, not receiving directly observed therapy, pulmonary disease, HIV/AIDS diagnosis, not having a family physician, being unemployed and using public transportation were predictors of recurrent disease. There was a significant increase in drug-resistant M. tuberculosis strains in the second episode of disease compared to the first episode (21.3% vs. 8.2%, P = 0.04). Exogenous re-infection with a new strain of M. tuberculosis was found to cause 24-31% of recurrent TB. CONCLUSION: Recurrent TB in Houston is associated with a significant increase in drug-resistant M. tuberculosis strains. Re-infection with a new M. tuberculosis strain causes a significant proportion of recurrent TB in an area of low TB incidence. Patients with HIV/AIDS constitute a population at increased risk of disease recurrence. C1 Baylor Coll Med, Dept Pathol 209E, Houston, TX 77030 USA. Univ Calif San Francisco, Keck Sch Med, Dept Med, Los Angeles, CA USA. NIH, Lab Human Bacterial Pathogenesis, Hamilton, MT USA. RP Graviss, EA (reprint author), Baylor Coll Med, Dept Pathol 209E, 1 Baylor Plaza, Houston, TX 77030 USA. EM egraviss@bcm.tmc.edu FU NIAID NIH HHS [N01-AO-02738] NR 38 TC 25 Z9 26 U1 0 U2 0 PU INT UNION AGAINST TUBERCULOSIS LUNG DISEASE (I U A T L D) PI PARIS PA 68 BOULEVARD SAINT-MICHEL,, 75006 PARIS, FRANCE SN 1027-3719 J9 INT J TUBERC LUNG D JI Int. J. Tuberc. Lung Dis. PD MAR PY 2004 VL 8 IS 3 BP 333 EP 340 PG 8 WC Infectious Diseases; Respiratory System SC Infectious Diseases; Respiratory System GA 817FZ UT WOS:000221164700010 PM 15139472 ER PT J AU He, MG Zeng, JW Liu, YZ Xu, JJ Pokharel, GP Ellwein, LB AF He, MG Zeng, JW Liu, YZ Xu, JJ Pokharel, GP Ellwein, LB TI Refractive error and visual impairment in urban children in southern China SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID SINGAPOREAN CHILDREN; MYOPIA PROGRESSION; SHUNYI DISTRICT; SCHOOLCHILDREN; POPULATION AB PURPOSE. To assess the prevalence of refractive error and visual impairment in school-age children in a metropolitan area of southern China. METHODS. Random selection of geographically defined clusters was used to identify children 5 to 15 years of age in Guangzhou. Children in 22 clusters were enumerated through a door-to-door survey and examined in 71 schools and 19 community facilities from October 2002 to January 2003. The examination included visual acuity measurements, ocular motility evaluation, retinoscopy, and autorefraction under cycloplegia and examination of the external eye, anterior segment, media, and fundus. RESULTS. A total of 5053 children living in 4814 households were enumerated, and 4364 (86.4%) were examined. The prevalence of uncorrected, presenting, and best-corrected visual acuity 20/40 or worse in the better eye was 22.3%, 10.3%, and 0.62%, respectively. Refractive error was the cause in 94.9% of the 2335 eyes with reduced vision, amblyopia in 1.9%, other causes in 0.4%, and unexplained causes in the remaining 2.8%. External and anterior segment abnormalities were seen in 1496 (34.3%) children, mainly minor conjunctival abnormalities. Media and fundus abnormalities were observed in 32 (0.73%) children. Myopia (spherical equivalent of at least -0.50 D in either eye) measured with retinoscopy affected 73.1% of children 15 years of age, 78.4% with autorefraction. The prevalence of myopia was 3.3% in 5-year-olds with retinoscopy and 5.7% with autorefraction. Females had a significantly higher risk of myopia. Hyperopia (+2.00 D or more) measured with retinoscopy was present in 16.7% of 5-year-olds, 17.0% with autorefraction. The prevalence of hyperopia was below 1% in 15-year-olds, with both methods. Astigmatism (cylinder of greater than or equal to0.75 D) was present in 33.6% of children with retinoscopy and in 42.7% with autorefraction. CONCLUSIONS. The prevalence of reduced vision because of myopia is high in school-age children living in metropolitan Guangzhou, representing an important public health problem. One third of these children do not have the necessary corrective spectacles. Effective strategies are needed to eliminate this easily treated cause of significant visual impairment. C1 NEI, NIH, Bethesda, MD 20892 USA. Zhongshan Ophthalm Ctr, Guangzhou, Peoples R China. World Hlth Org, Prevent Blindness & Deafness, Geneva, Switzerland. RP Ellwein, LB (reprint author), NEI, NIH, 31 Ctr Dr,MSC 2510, Bethesda, MD 20892 USA. EM ellweinl@nei.nih.gov OI He, Mingguang/0000-0002-6912-2810 FU NEI NIH HHS [N0-EY-2103] NR 20 TC 330 Z9 354 U1 5 U2 44 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR PY 2004 VL 45 IS 3 BP 793 EP 799 DI 10.1167/iovs.03-1051 PG 7 WC Ophthalmology SC Ophthalmology GA 776QZ UT WOS:000189129200015 PM 14985292 ER PT J AU Ham, DI Kim, SJ Chen, J Vistica, BP Fariss, RX Lee, RS Wawrousek, EF Takase, H Yu, CR Egwuagu, CE Chan, CC Gery, I AF Ham, DI Kim, SJ Chen, J Vistica, BP Fariss, RX Lee, RS Wawrousek, EF Takase, H Yu, CR Egwuagu, CE Chan, CC Gery, I TI Central immunotolerance in transgenic mice expressing a foreign antigen under control of the rhodopsin promoter SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID T-CELL TOLERANCE; NEO-SELF ANTIGEN; THYMIC EPITHELIAL-CELLS; NEGATIVE SELECTION; AUTOIMMUNE UVEORETINITIS; GENE-EXPRESSION; B-CELLS; INDUCTION; DISEASE; AUTOANTIGENS AB PURPOSE. Different conclusions have been reached in recent studies concerning the immune response or tolerance of transgenic (Tg) mice expressing foreign antigens under control of retinal antigen promoters. The present study was aimed at analyzing the state of tolerance in Tg mice expressing hen egg lysozyme (HEL) under control of the rhodopsin promoter. METHODS. Tg mice expressing HEL under control of the rhodopsin promoter (RhHEL-Tg) were generated and tested by conventional methods for immune responses against HEL. These Tg mice were also mated with Tg mice expressing HEL-specific receptor on their T lymphocytes and the double-Tg mice were examined for increased apoptosis in their thymi by the TUNEL assay, as well as for loss of HEL-specific T cells, by flow cytometry and proliferative response. The presence of HEL mRNA in mouse thymi was determined by RTPCR. RESULTS. RhHEL-Tg mice developed tolerance to HEL, shown by reduced cellular and humoral responses to HEL, as well as by the failure of ocular inflammation to develop after immunization with HEL. RhHEL-Tg mice expressed HEL mRNA in their thymus, and the tolerogenic mechanism in these mice was shown to be thymic deletion of HEL-specific T cells by the following observations in the double-Tg mice: (1) increased apoptosis in their thymi, (2) remarkable reduction in the proportion of the HEL-specific T cells, and (3) loss of lymphocyte response to low concentrations of HEL. CONCLUSIONS. Tg mice expressing HEL under control of the rhodopsin promoter develop a tolerance for the foreign antigen, apparently as a result of thymic expression of HEL and deletion of T cells specific to this antigen. C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. NEI, Lab Mech Ocular Dis, NIH, Bethesda, MD 20892 USA. NEI, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. Sungkyunkwan Univ, Dept Ophthalmol, Sch Med, Seoul, South Korea. Howard Hughes Med Inst, NIH, Res Scholars Program, Bethesda, MD 20817 USA. RP Gery, I (reprint author), NEI, Immunol Lab, NIH, Bldg 10,Room 10N112, Bethesda, MD 20892 USA. EM igery@helix.nih.gov RI Wawrousek, Eric/A-4547-2008 NR 32 TC 18 Z9 19 U1 0 U2 3 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR PY 2004 VL 45 IS 3 BP 857 EP 862 DI 10.1167/iovs.03-1028 PG 6 WC Ophthalmology SC Ophthalmology GA 776QZ UT WOS:000189129200026 PM 14985302 ER PT J AU Tan, FG Donovan, AK Ledee, DR Zelenka, PS Fariss, RN Chepelinsky, AB AF Tan, FG Donovan, AK Ledee, DR Zelenka, PS Fariss, RN Chepelinsky, AB TI gamma E-crystallin recruitment to the plasma membrane by specific interaction between lens MIP/aquaporin-0 and gamma E-crystallin SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID MAJOR INTRINSIC PROTEIN; EYE LENS; GENE FAMILY; MOUSE LENS; RAT LENS; CONGENITAL CATARACTS; MURINE CATARACT; MIP; MUTATION; EXPRESSION AB PURPOSE. Major intrinsic protein (MIP), also called aquaporin-0, is essential for lens transparency and is specifically expressed in the lens fiber cell membranes. The goal of the current study was to identify and characterize proteins that interact with MIP and to elucidate the role of these interactions in MIP functions. METHODS. The C-terminal 74-amino-acid fragment of MIP was used as bait to screen a rat lens cDNA yeast two-hybrid library. The full-length MIP was expressed as enhanced green fluorescent protein (EGFP)-tagged or myc-tagged proteins, and gammaE-crystallin was expressed as FLAG-tagged or red fluorescent protein (HcRed)-tagged proteins, respectively, in the RK13 rabbit kidney epithelial cell line. Protein-protein interactions were analyzed by coimmunoprecipitation assays and visualized by confocal fluorescence microscopy. RESULTS. gammaE-Crystallin, a water-soluble protein that is specifically expressed in lens fibers, was identified as a binding protein to the MIP C-terminal peptide. Coimmunoprecipitation assays demonstrated that gammaE-crystallin interacts specifically with full-length MIP in mammalian cells. MIP did not interact with gammaD-crystallin, another member of the highly conserved gamma-crystallin gene family. Confocal fluorescence microscopy demonstrated that MIP interacted with gammaE-crystallin in individual mammalian cells and that this interaction resulted in the recruitment of gammaE-crystallin from the cytoplasm to the plasma membrane. CONCLUSIONS. These experiments provide the first demonstration of MIP interaction with other lens proteins at the molecular level and raise the possibility of a structural role of MIP in the organization of gamma-crystallins in lens fibers. C1 NEI, NIH, Mol & Dev Biol Lab, Bethesda, MD 20892 USA. NEI, NIH, Lab Mechanisms Ocular Dis, Bethesda, MD 20892 USA. RP Chepelinsky, AB (reprint author), NEI, NIH, Mol & Dev Biol Lab, 7 Med Dr,MSC 0704,Bldg 7,Room 105, Bethesda, MD 20892 USA. EM abc@helix.nih.gov NR 47 TC 1 Z9 1 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR PY 2004 VL 45 IS 3 BP 863 EP 871 PG 9 WC Ophthalmology SC Ophthalmology GA 776QZ UT WOS:000189129200027 ER PT J AU Ebong, S Yu, CR Carper, DA Chepelinsky, AB Egwuagu, CE AF Ebong, S Yu, CR Carper, DA Chepelinsky, AB Egwuagu, CE TI Activation of STAT signaling pathways and induction of suppressors of cytokine signaling (SOCS) proteins in mammalian lens by growth factors SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID FIBER CELL-DIFFERENTIATION; TRANSGENIC MICE; MOUSE LENS; TRANSCRIPTION FACTORS; GENE-EXPRESSION; INHIBITION; DRUG AB PURPOSE. This study was conducted to examine whether the effects of growth factors are mediated in the lens by Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathways and whether they induce expression of suppressors of cytokine signaling (SOCS), a novel family of feedback regulators of cytokine and growth factor activities. METHODS. STAT activation and SOCS expression were analyzed in transgenic or wild-type mouse lens and lens epithelial cells stimulated with growth factors by immunohistochemistry, RTPCR, Northern, Western, proliferation, or transient reporter assays. RESULTS. STATs were constitutively expressed at low levels and activated by insulin-like growth factor (IGF)-1, platelet-derived growth factor (PDGF)-aa, and FGF-1 or -2 in the lens. The Intensity of STAT signaling increased at high FGF-2 concentration and FGFs act in synergy with IGF-1 or PDGFaa to enhance STAT signaling and SOCS expression. Growth factor-induced proliferation of lens cells is inhibited by AG-490, a specific inhibitor of JAK2/STAT3. CONCLUSIONS. This is the first report that FGFs activate STAT pathways in the lens and that SOCS proteins are constitutively expressed and upregulated by growth factors in this tissue. Physiological relevance of STAT pathways in the lens is underscored by inhibition of lens cell proliferation by inhibitors of JAK/STAT pathways and by the aberrant proliferation of lens epithelium in the posterior pole of transgenic mice with constitutively activated STAT1 in the lens. Common activation of STAT pathways by FGF-1, FGF-2, IGF-1, or PDGFaa and their synergistic activation of STATs and SOCS in lens cells suggest that activities and crosstalk between these factors are sensitive to the steady state levels of activated STATs in the lens and may be under feedback regulation by SOCS family proteins. C1 NEI, Mol Immunol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. NEI, Lab Mechanisms Ocular Dis, NIH, Bethesda, MD 20892 USA. NEI, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RP Egwuagu, CE (reprint author), NEI, Mol Immunol Sect, Immunol Lab, NIH, Bldg 10,Room 10N116,10 Ctr Dr, Bethesda, MD 20892 USA. EM emeka@helix.nih.gov NR 30 TC 24 Z9 27 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR PY 2004 VL 45 IS 3 BP 872 EP 878 DI 10.1167/iovs.03-0311 PG 7 WC Ophthalmology SC Ophthalmology GA 776QZ UT WOS:000189129200028 PM 14985304 ER PT J AU Wohl, DA Pilcher, CD Evans, S Revuelta, M McComsey, G Yang, YJ Zackin, R Alston, B Welch, S Basar, M Kashuba, A Kondo, P Martinez, A Giardini, J Quinn, J Littles, M Wingfield, H Koletar, SL AF Wohl, DA Pilcher, CD Evans, S Revuelta, M McComsey, G Yang, YJ Zackin, R Alston, B Welch, S Basar, M Kashuba, A Kondo, P Martinez, A Giardini, J Quinn, J Littles, M Wingfield, H Koletar, SL CA Adult AIDS Clinical Trials Grp A51 TI Absence of sustained hyperlactatemia in HIV-infected patients with risk factors for mitochondrial toxicity SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE hyperlactatemia; lactate; nucleosides analogues; mitochondrial toxicity ID LACTIC-ACIDOSIS; ANTIRETROVIRAL THERAPY; DIDANOSINE THERAPY; HEPATIC STEATOSIS; LACTATE LEVELS; PANCREATITIS; STAVUDINE AB Background: The prevalence of asymptomatic hyperlactatemia among HIV-infected individuals has been reported to be 4% to 36%. This variability may reflect differences in the definition of and risk factors for hyperlactatemia and/or techniques for venous lactate collection. Methods: We examined the prevalence of elevated venous lactate collected in accordance with Adult AIDS Clinical Trials Group (AACTG) guidelines among HIV-infected and nucleoside analogue-treated subjects with risk factors associated with hyperlactatemia. Sustained hyperlactaternia was defined as 2 consecutive levels greater than or equal to1.5 but less than or equal to4 times the upper limit of normal (ULN) within 30 days. Results: Eighty-three subjects were enrolled. Two thirds had greater than or equal to2 risk factors, with 11% having >4 risk factors. The median entry venous lactate level was 1.2 mmol/L (range: 0.7-5.1 mmol/L). Two subjects had a lactate level >1.5 times the ULN: 1 with a value of 2.1 times the ULN at entry and a week 2 level of 1.2 times the ULN and a second subject with a week 2 value of 1.9 times the ULN but an entry level of 1.4 times the ULN. The latter subject developed symptomatic lactic acidosis 3 weeks following study discontinuation. Conclusions: Sustained asymptomatic hyperlactatemia among subjects with risk factors associated with hyperlactaternia was not observed when venous lactate was measured in a standardized fashion. One case of hyperlactaternia that evolved into symptomatic lactic acidosis was diagnosed soon after the completion of the study, however. Our findings indicate that asymptomatic hyperlactaternia is either very rare or an artifact of collection technique. C1 Univ N Carolina, Dept Med, Chapel Hill, NC USA. Harvard Univ, Sch Publ Hlth, Stat & Data Anal Ctr, Boston, MA 02115 USA. Beth Israel Med Ctr, Dept Med, New York, NY 10003 USA. Case Western Reserve Univ, Dept Med, Cleveland, OH 44106 USA. Case Western Reserve Univ, Dept Pediat, Cleveland, OH 44106 USA. NIH, Div Aids, Bethesda, MD USA. Social & Sci Syst, Silver Spring, MD USA. Frontier Sci & Technol Res Fdn Inc, Complicat Sect, Amherst, NY USA. Univ N Carolina, Sch Pharm, Div Pharmacotherapy, Chapel Hill, NC USA. Univ Hawaii, Retrovirol Res Lab, Honolulu, HI 96822 USA. NIH, Pharmacol Affairs Branch, Div Aids, Bethesda, MD USA. Frontier Sci & Technol Res Fdn Inc, Amherst, NY USA. Univ Penn, AIDS Clin Trials Unit, Philadelphia, PA USA. Mt Sinai Sch Med, AIDS Clin Trials Unit, New York, NY USA. Univ Alabama, AIDS Clin Trials Unit, Birmingham, AL USA. Ohio State Univ, Dept Med, Columbus, OH 43210 USA. RP Wohl, DA (reprint author), 211A W Cameron Ave, Chapel Hill, NC 27599 USA. EM wohl@med.unc.edu FU NCRR NIH HHS [RR00080, RR00046]; NIAID NIH HHS [AI-46370, 9P30 AI50410, AI-25924, AI-25868-15, AI-25879] NR 28 TC 12 Z9 13 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD MAR 1 PY 2004 VL 35 IS 3 BP 274 EP 278 DI 10.1097/00126334-200403010-00008 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 804WA UT WOS:000220327600008 PM 15076242 ER PT J AU Miyanaga, M Kiyosawa, M Takase, H Eishi, Y Shen, DF Chan, CC Mochizuki, M AF Miyanaga, M Kiyosawa, M Takase, H Eishi, Y Shen, DF Chan, CC Mochizuki, M TI Microdissection and gene rearrangement analysis of paraffin-embedded specimens of orbital malignant lymphoma SO JAPANESE JOURNAL OF OPHTHALMOLOGY LA English DT Article DE immunoglobulin gene rearrangement; microdissection; orbital malignant lymphoma; paraffin-embedded specimen; polymerase chain reaction ID POLYMERASE-CHAIN-REACTION; B-CELL LYMPHOMA; INTRAOCULAR LYMPHOMA; DIAGNOSIS; TISSUES; IMMUNOHISTOCHEMISTRY; HYPERPLASIA; ANTIBODIES; UTILITY AB Purpose: To determine whether a definite diagnosis of malignant lymphoma can be made from paraffin-embedded archived orbital specimens by gene rearrangement analysis using microdissection and polymerase chain reaction (PCR). Methods: Specimens from four patients with histopathologically diagnosed orbital malignant lymphoma were examined. The malignant cells were microdissected off the paraffin-embedded specimens. DNA was extracted from the cells, and the immunoglobulin heavy chain (IgH) gene was amplified by PCR. Gene rearrangements were detected by using primers for the third framework (FR3A), the second framework (FR2A), and the complementary determining region 3 (CDR3). Translocation of the B-cell lymphoma/leukemia-2 (bcl-2) gene was also examined. Results: Malignant cells were present on the slides of the paraffin-embedded specimens of three of four cases. The specimens from these three cases showed IgH rearrangements for FR3A, FR2A, and CDR3. A bcl-2-associated translocation was also detected in one case. Conclusions: Gene rearrangement analysis is applicable to paraffin-embedded archived orbital specimens to confirm a diagnosis of malignant lymphoma. The advantage of this method is that only a small specimen is needed because the detection sensitivity is high. (C) Japanese Ophthalmological Society 2004. C1 Tokyo Med & Dent Univ, Grad Sch, Dept Ophthalmol & Visual Sci, Bunkyo Ku, Tokyo 11398591, Japan. Tokyo Med & Dent Univ, Grad Sch, Dept Surg Pathol, Tokyo 11398591, Japan. NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Kiyosawa, M (reprint author), Tokyo Med & Dent Univ, Grad Sch, Dept Ophthalmol & Visual Sci, Bunkyo Ku, 1-5-45 Yushima, Tokyo 11398591, Japan. EM m.kiyosawa.oph@tmd.ac.jp NR 21 TC 1 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 0021-5155 J9 JPN J OPHTHALMOL JI Jpn. J. Ophthalmol. PD MAR-APR PY 2004 VL 48 IS 2 BP 123 EP 127 DI 10.1007/s10384-003-0038-7 PG 5 WC Ophthalmology SC Ophthalmology GA 810VB UT WOS:000220730700006 PM 15060790 ER PT J AU Tohen, M Zarate, CA Hennen, J Khalsa, HMK Strakowski, SM Gebre-Medhin, P Salvatore, P Baldessarini, RJ AF Tohen, M Zarate, CA Hennen, J Khalsa, HMK Strakowski, SM Gebre-Medhin, P Salvatore, P Baldessarini, RJ TI Prediction of recovery and recurrence in patients with first episode mania SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Meeting Abstract C1 Lilly Res Labs, Indianapolis, IN USA. Harvard Univ, Sch Med, Consolidated Dept Psychiat, Boston, MA USA. Harvard Univ, Sch Med, Neurosci Program, Boston, MA USA. McLean Hosp, Int Consortium Bipolar Diosorders Res, Belmont, MA 02178 USA. NIMH, Mood Disorders Res Unit, Bethesda, MD 20892 USA. Univ Cincinnati, Dept Psychiat, Cincinnati, OH USA. Univ Med Ctr, Inst Psychiat, Fac Med, Parma, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD MAR PY 2004 VL 78 SU 1 BP S5 EP S6 PG 2 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 808UN UT WOS:000220594100007 ER PT J AU Netzel-Arnett, S Haudenschild, CC Bugge, TH Antalis, TM AF Netzel-Arnett, S Haudenschild, CC Bugge, TH Antalis, TM TI On the biological function of testisin: A membrane serine protease expressed specifically during spermatogenesis SO JOURNAL OF ANDROLOGY LA English DT Meeting Abstract CT 29th Annual Meeting of the American-Society-of-Andrology (ASA 2004) CY APR 17-20, 2004 CL Baltimore, MD SP Amer Soc Androl C1 Amer Red Cross, Jerome H Holland Lab Biomed Res, Rockville, MD USA. Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC ANDROLOGY, INC PI LAWRENCE PA C/O ALLEN PRESS, INC PO BOX 368, LAWRENCE, KS 66044 USA SN 0196-3635 J9 J ANDROL JI J. Androl. PD MAR-APR PY 2004 SU S MA 51 BP 55 EP 55 PG 1 WC Andrology SC Endocrinology & Metabolism GA 803LE UT WOS:000220231800052 ER PT J AU Gaponenko, V Sarma, SP Altieri, AS Horita, DA Li, J Byrd, RA AF Gaponenko, V Sarma, SP Altieri, AS Horita, DA Li, J Byrd, RA TI Improving the accuracy of NMR structures of large proteins using pseudocontact shifts as long-range restraints SO JOURNAL OF BIOMOLECULAR NMR LA English DT Article DE deuteration; ILV-labeling; NMR structural accuracy; pseudocontact shifts; residual dipolar coupling; STAT4 ID RESIDUAL DIPOLAR COUPLINGS; NUCLEAR-MAGNETIC-RESONANCE; LIQUID-CRYSTALLINE MEDIUM; DE-NOVO DETERMINATION; CHEMICAL-SHIFT; BACKBONE STRUCTURE; GLOBAL FOLDS; MACROMOLECULES; SPECTROSCOPY; DOMAIN AB We demonstrate improved accuracy in protein structure determination for large (greater than or equal to 30 kDa), deuterated proteins (e.g. STAT4(NT)) via the combination of pseudocontact shifts for amide and methyl protons with the available NOEs in methyl-protonated proteins. The improved accuracy is cross validated by Q-factors determined from residual dipolar couplings measured as a result of magnetic susceptibility alignment. The paramagnet is introduced via binding to thiol-reactive EDTA, and multiple sites can be serially engineered to obtain data from alternative orientations of the paramagnetic anisotropic susceptibility tensor. The technique is advantageous for systems where the target protein has strong interactions with known alignment media. C1 NCI, Struct Biophys Lab, Frederick, MD 21702 USA. RP Byrd, RA (reprint author), NCI, Struct Biophys Lab, POB B, Frederick, MD 21702 USA. EM rabyrd@ncifcrf.gov RI Byrd, R. Andrew/F-8042-2015; OI Byrd, R. Andrew/0000-0003-3625-4232; Horita, David/0000-0002-9563-107X NR 36 TC 67 Z9 67 U1 0 U2 15 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0925-2738 J9 J BIOMOL NMR JI J. Biomol. NMR PD MAR PY 2004 VL 28 IS 3 BP 205 EP 212 DI 10.1023/B:JNMR.0000013706.09264.36 PG 8 WC Biochemistry & Molecular Biology; Spectroscopy SC Biochemistry & Molecular Biology; Spectroscopy GA 768FD UT WOS:000188532200001 PM 14752254 ER PT J AU Bryce, DL Bax, A AF Bryce, DL Bax, A TI Application of correlated residual dipolar couplings to the determination of the molecular alignment tensor magnitude of oriented proteins and nucleic acids SO JOURNAL OF BIOMOLECULAR NMR LA English DT Article DE alignment tensor; dipolar coupling; histogram; liquid crystal; molecular alignment; powder pattern; residual dipolar couplings; RNA ID LIQUID-CRYSTALLINE PHASE; MALTODEXTRIN-BINDING-PROTEIN; DIRECT STRUCTURE REFINEMENT; BIOLOGICAL MACROMOLECULES; POLYACRYLAMIDE GELS; HETERONUCLEAR NMR; ROTATING SOLIDS; WEIGHT PROTEINS; MODEL PEPTIDES; MAGNETIC-FIELD AB Residual dipolar couplings (RDC) between nuclear spins in partially aligned samples offer unique insights into biomacromolecular structure and dynamics. To fully benefit from the RDC data, accurate knowledge of the magnitude (D-a) and rhombicity (R) of the molecular alignment tensor, A, is important. An extended histogram method (EHM) is presented which extracts these parameters more effectively from dipolar coupling data. The method exploits the correlated nature of RDCs for structural elements of planar geometry, such as the one-bond C-13'(i)- C-13(i)alpha, C-13(i)'- N-15(i+1), and N-15(i+1)- H-1(i+1)N couplings in peptide bonds of proteins, or suitably chosen combinations of D-1(C1'H1'), D-1(C2'H2)', D-1(C1'C2)', D-2(C2'H1)', D-2(C1'H2'), and D-3(H1'H2') couplings in nucleic acids, to generate an arbitrarily large number of synthetic RDCs. These synthetic couplings result in substantially improved histograms and resulting values of D-a and R, compared with histograms generated solely from the original sets of correlated RDCs, particularly when the number of planar fragments for which couplings are available is small. An alternative method, complementary to the EHM, is also described, which uses a systematic grid search procedure, based on least-squares fitting of sets of correlated RDCs to structural elements of known geometry, and provides an unambiguous lower limit for the degree of molecular alignment. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Bax, A (reprint author), NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. EM bax@nih.gov RI Bryce, David/A-3534-2008 OI Bryce, David/0000-0001-9989-796X NR 60 TC 32 Z9 32 U1 0 U2 3 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0925-2738 J9 J BIOMOL NMR JI J. Biomol. NMR PD MAR PY 2004 VL 28 IS 3 BP 273 EP 287 DI 10.1023/B:JNMR.0000013701.16162.0c PG 15 WC Biochemistry & Molecular Biology; Spectroscopy SC Biochemistry & Molecular Biology; Spectroscopy GA 768FD UT WOS:000188532200007 PM 14752260 ER PT J AU Leet, AI Magur, E Lee, JS Wientroub, S Robey, PG Collins, MT AF Leet, AI Magur, E Lee, JS Wientroub, S Robey, PG Collins, MT TI Fibrous dysplasia in the spine: Prevalence of lesions and association with scoliosis SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID THORACIC SPINE; LUMBAR SPINE AB Background: Lesions of fibrous dysplasia involving the spine and scoliosis are thought to be uncommon entities in patients with polyostotic fibrous dysplasia and McCune-Albright syndrome. By examining bone scans of a relatively large cohort of patients with these disorders, we sought to determine the prevalence of spinal involvement and any association with scoliosis. Methods: Sixty-two patients with polyostotic fibrous dysplasia were studied. There were twenty-three male and thirty-nine female patients, and they had a mean age of twenty-five years (range, four to eighty years). Technetium-99m-methylene diphosphonate (MDP) bone scans of the patients were evaluated for evidence of increased uptake in the spine. The presence or absence of scoliosis or a level pelvis and the distribution of other lesions in the skeleton were noted. Results: Thirty-nine (63%) of sixty-two patients were found to have seventy-six lesions of fibrous dysplasia in the spine. Fifty-four lesions (71%) demonstrated increased uptake in the posterior aspects of the spine. Most lesions were located in the lumbar spine (thirty-two lesions) and the thoracic spine (twenty-seven), with less frequent involvement in the sacrum (ten) and cervical spine (six). Twenty-five (40%) of the sixty-two patients had scoliosis; seventeen had a thoracolumbar curve; six, a lumbar curve; and two, a thoracic curve. Seven patients had curves that could not be accurately measured by bone scanning and, therefore, could not be classified. Thirty patients (48%) had no evidence of scoliosis. Thus, the prevalence of scoliosis in patients with polyostotic fibrous dysplasia was between 40% and 52%. There was a strong correlation between spinal lesions and scoliosis (p < 0.001) and pelvic asymmetry (p < 0.05). Back pain was an uncommon symptom. Two patients had a neurologic abnormality; neither abnormality was related to the location of the lesions or the curve. Conclusions: Spinal lesions and scoliosis may be more common in patients with polyostotic fibrous dysplasia than has been previously reported. Since there is a strong correlation between a spinal lesion and scoliosis, these patients should be screened clinically for scoliosis. Level of Evidence: Prognostic study, Level II-1 (retrospective study). See Instructions to Authors for a complete description of levels of evidence. C1 Georgetown Univ, Dept Orthopaed, Washington, DC 20007 USA. Univ Calif San Francisco, Dept Oral & Maxillofacial Surg, San Francisco, CA 94143 USA. Tel Aviv Souraksy Med Ctr, Dana Childrens Hosp, Dept Pediat Orthoped Surg, IL-64239 Tel Aviv, Israel. Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD USA. RP Leet, AI (reprint author), Johns Hopkins Med, Dept Orthopaed, 601 N Caroline St,Room 5255, Baltimore, MD 21287 USA. EM aleet1@jhmi.edu RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 24 TC 32 Z9 34 U1 0 U2 1 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD MAR PY 2004 VL 86A IS 3 BP 531 EP 537 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 779AF UT WOS:000189272900011 PM 14996879 ER PT J AU Baysac, MAS Horowitz, AM Ma, DS AF Baysac, MAS Horowitz, AM Ma, DS TI Oral cancer information in health education textbooks SO JOURNAL OF CANCER EDUCATION LA English DT Article ID KNOWLEDGE; NECK; HEAD; RISK AB Background. Previous studies have reported a lack of knowledge and misinformation about oral cancer, its risk factors, and preventive methods among the general public. This study evaluated the quality, completeness, and accuracy of oral cancer information in 26 health education (elementary to high school) textbooks. Methods. Twenty-six health education textbooks were purchased and evaluated. Results. A deficiency in the amount, accuracy, and quality of oral cancer information in grade school and high school textbooks was evident. Conclusion. Current health texts do not provide adequate information to educate future adults about oral cancer prevention and early detection. C1 NIDCR, NIH, Bethesda, MD 20892 USA. Univ Calif San Francisco, Sch Dent, San Francisco, CA 94143 USA. RP Horowitz, AM (reprint author), NIDCR, NIH, 45 Ctr Dr,Room 4AS-37A, Bethesda, MD 20892 USA. EM Alice.Horowitz@nih.gov NR 24 TC 4 Z9 4 U1 0 U2 2 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 0885-8195 J9 J CANCER EDUC JI J. Cancer Educ. PD SPR PY 2004 VL 19 IS 1 BP 12 EP 16 DI 10.1207/s15430154jce1901_07 PG 5 WC Oncology; Education, Scientific Disciplines; Public, Environmental & Occupational Health SC Oncology; Education & Educational Research; Public, Environmental & Occupational Health GA 814ZT UT WOS:000221013300006 PM 15059751 ER PT J AU Mongeau, SW Horowitz, AM Horowitz, AM AF Mongeau, SW Horowitz, AM Horowitz, AM TI Assessment of reading level and content adequacy of oral cancer educational materials from USAF dental clinics SO JOURNAL OF CANCER EDUCATION LA English DT Article ID KNOWLEDGE; NECK; HEAD; RISK AB Background. The threat of oral cancer has generated growing concern among the military health community that its beneficiaries have access to appropriate printed health materials. This study addresses the reading level and content adequacy of printed oral cancer literature collected from 82 United States Air Force (USAF) dental clinics. Methods. Materials were subjected to a readability formula and information content analysis. Results. Readability ranged from 7th to 13th grade, consistent with the lowest grade level (high school) required for USAF personnel. Adequacy of the content of materials was highly variable. Conclusion. Few oral cancer items were retrieved, most were old, and many included misleading or incorrect information. C1 NIDCR, NIH, Bethesda, MD 20892 USA. RP Horowitz, AM (reprint author), NIDCR, NIH, 45 Ctr Dr,Room 4AS-37A, Bethesda, MD 20892 USA. EM Alice.Horowitz@nih.gov NR 28 TC 3 Z9 4 U1 0 U2 1 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 0885-8195 J9 J CANCER EDUC JI J. Cancer Educ. PD SPR PY 2004 VL 19 IS 1 BP 29 EP 36 DI 10.1207/s15430154jce1901_09 PG 8 WC Oncology; Education, Scientific Disciplines; Public, Environmental & Occupational Health SC Oncology; Education & Educational Research; Public, Environmental & Occupational Health GA 814ZT UT WOS:000221013300008 PM 15059753 ER EF