FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Liu, SY Michishita, E Park, JY Nunez, N Hursting, SD Barrett, C Horikawa, I AF Liu, SY Michishita, E Park, JY Nunez, N Hursting, SD Barrett, C Horikawa, I TI Analysis of mammalian SIRT6, a homolog of the yeast Sir2 protein, during adipogenesis and calorie-restriction. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 4th Annual Conference on Frontiers in Cancer Prevention Research CY OCT 30-NOV 02, 2005 CL Baltimore, MD C1 NCI, Bethesda, MD 20892 USA. Howard Hughes Med Inst, Chevy Chase, MD USA. NR 0 TC 2 Z9 2 U1 0 U2 3 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 NOV PY 2005 VL 14 IS 11 SU S BP 2731S EP 2731S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 985BN UT WOS:000233351200207 ER PT J AU Adams, K Albanes, D Leitzmann, M Kipnis, V Midthune, D Subar, AF Hollenbeck, A Schatzkin, A AF Adams, K Albanes, D Leitzmann, M Kipnis, V Midthune, D Subar, AF Hollenbeck, A Schatzkin, A TI The fat but fit hypothesis and colon cancer: Does obesity make any difference if you re active? Results from the NIH-AARP study. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 4th Annual Conference on Frontiers in Cancer Prevention Research CY OCT 30-NOV 02, 2005 CL Baltimore, MD C1 NCI, Rockville, MD USA. AARP, Washington, DC USA. RI Albanes, Demetrius/B-9749-2015 NR 0 TC 0 Z9 0 U1 0 U2 1 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 NOV PY 2005 VL 14 IS 11 SU S BP 2732S EP 2732S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 985BN UT WOS:000233351200210 ER PT J AU Hursting, S Nunez, N Libutti, S Keck, V Connor, S Smith, N Varticovski, L Perkins, S Barrett, C AF Hursting, S Nunez, N Libutti, S Keck, V Connor, S Smith, N Varticovski, L Perkins, S Barrett, C TI Obesity, wound healing, and mammary cancer: Impact of ovarian hormone status. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 4th Annual Conference on Frontiers in Cancer Prevention Research CY OCT 30-NOV 02, 2005 CL Baltimore, MD C1 Univ Texas, Austin, TX 78712 USA. NCI, Bethesda, MD 20892 USA. Novartis Inc, Cambridge, MA USA. NR 0 TC 0 Z9 0 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 NOV PY 2005 VL 14 IS 11 SU S BP 2732S EP 2732S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 985BN UT WOS:000233351200209 ER PT J AU Flood, A Cash, B Schatzkin, A Schoenfeld, P AF Flood, A Cash, B Schatzkin, A Schoenfeld, P TI Lifestyle and demographic risk factors for adenomatous polyps in a colorectal cancer screening study of asymptomatic women. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 4th Annual Conference on Frontiers in Cancer Prevention Research CY OCT 30-NOV 02, 2005 CL Baltimore, MD C1 Natl Naval Med Res Inst, Bethesda, MD 20892 USA. Univ Minnesota, Minneapolis, MN USA. NCI, Sch Med, Bethesda, MD USA. Univ Michigan, Ann Arbor, MI USA. NR 0 TC 0 Z9 0 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 NOV PY 2005 VL 14 IS 11 SU S BP 2733S EP 2733S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 985BN UT WOS:000233351200216 ER PT J AU Hou, LF El-Omar, ME Dott, PG Rabkin, C Baccarelli, A Yeager, M Chanock, SJ Zatonski, W Chen, JB Lissowska, J AF Hou, LF El-Omar, ME Dott, PG Rabkin, C Baccarelli, A Yeager, M Chanock, SJ Zatonski, W Chen, JB Lissowska, J TI Polymorphisms in genes involved in Th1-type cell-mediated response and the risk of gastric cancer in a polish population. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 4th Annual Conference on Frontiers in Cancer Prevention Research CY OCT 30-NOV 02, 2005 CL Baltimore, MD C1 NCI, Rockville, MD USA. Univ Aberdeen, Inst Med Sci, Dept Med & Therapeut, Aberdeen, Scotland. Univ Milan, Maggiore Hosp IRCCS Fdn, Milan, Italy. NCI, Core Genotyping Facil, Ctr Adv Technol, Gaithersburg, MD USA. Ctr Canc, Div Canc Epidemiol & Prevent, Warsaw, Poland. M Sklodowska Curie Inst Oncol, Warsaw, Poland. NR 0 TC 0 Z9 0 U1 1 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 NOV PY 2005 VL 14 IS 11 SU S BP 2735S EP 2735S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 985BN UT WOS:000233351200222 ER PT J AU Myers, RE Weinberg, DS Miller-Samuel, S Cocroft, J Manne, SL Wilfond, B AF Myers, RE Weinberg, DS Miller-Samuel, S Cocroft, J Manne, SL Wilfond, B TI Decision counseling and colorectal cancer genetic-environmental risk assessment. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 4th Annual Conference on Frontiers in Cancer Prevention Research CY OCT 30-NOV 02, 2005 CL Baltimore, MD C1 Thomas Jefferson Univ, Philadelphia, PA 19107 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. NHGRI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 NOV PY 2005 VL 14 IS 11 SU S BP 2736S EP 2737S PN 2 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 985BN UT WOS:000233351200229 ER PT J AU Wanke, KL Bergen, AW Sansbury, L Cantwell, M Caporaso, N Lehman, TA Kalidindi, A Modali, R Albert, P Ratnasinghe, L Lanza, E AF Wanke, KL Bergen, AW Sansbury, L Cantwell, M Caporaso, N Lehman, TA Kalidindi, A Modali, R Albert, P Ratnasinghe, L Lanza, E TI Polymorphisms associated with dietary-goal adherence in the polyp prevention trial. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 4th Annual Conference on Frontiers in Cancer Prevention Research CY OCT 30-NOV 02, 2005 CL Baltimore, MD C1 NCI, Bethesda, MD 20892 USA. Bioserve Biotechnol Ltd, Laurel, MD USA. Univ Arkansas, Little Rock, AR 72204 USA. NR 0 TC 0 Z9 0 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 NOV PY 2005 VL 14 IS 11 SU S BP 2737S EP 2738S PN 2 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 985BN UT WOS:000233351200233 ER PT J AU Kamangar, F Dawsey, SM Abnet, CC Pietinen, P Albanes, D Virtamo, J Taylor, PR AF Kamangar, F Dawsey, SM Abnet, CC Pietinen, P Albanes, D Virtamo, J Taylor, PR TI Serum pepsinogens and risk of gastric cardia and noncardia cancers: A prospective study of 22,000 subjects. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 4th Annual Conference on Frontiers in Cancer Prevention Research CY OCT 30-NOV 02, 2005 CL Baltimore, MD C1 NCI, Bethesda, MD 20892 USA. Finland Natl Publ Hlth Inst, Helsinki, Finland. RI Albanes, Demetrius/B-9749-2015 NR 0 TC 0 Z9 0 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 NOV PY 2005 VL 14 IS 11 SU S BP 2738S EP 2739S PN 2 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 985BN UT WOS:000233351200236 ER PT J AU Kassis, JN Guancial, EA Doong, H Virador, V Kohn, EC AF Kassis, JN Guancial, EA Doong, H Virador, V Kohn, EC TI CAIR-1/BAG-3 regulates tumor cell adhesion and migration by modulating signaling of focal adhesion signalosomes. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 4th Annual Conference on Frontiers in Cancer Prevention Research CY OCT 30-NOV 02, 2005 CL Baltimore, MD C1 NCI, Bethesda, MD 20892 USA. NIH, Howard Hughes Med Inst, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 NOV PY 2005 VL 14 IS 11 SU S BP 2743S EP 2744S PN 2 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 985BN UT WOS:000233351200257 ER PT J AU Irons, R Carlson, BA Hatfield, DL Davis, CD AF Irons, R Carlson, BA Hatfield, DL Davis, CD TI Dietary selenium (Se) and selenoproteins are important for protection against aberrant crypt formation in mice expressing a mutant selenocysteine tRNA([Ser]Sec). SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 4th Annual Conference on Frontiers in Cancer Prevention Research CY OCT 30-NOV 02, 2005 CL Baltimore, MD C1 NCI, NIH, Div Canc Prevent, Nutr Sci Res Grp, Bethesda, MD 20892 USA. NCI, NIH, Lab Canc Prevent, Mol Biol Selenium Sect, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 NOV PY 2005 VL 14 IS 11 SU S BP 2744S EP 2745S PN 2 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 985BN UT WOS:000233351200261 ER PT J AU Rogers, CJ Hance, KW Zaharoff, DA Perkins, SN Schlom, J Hursting, SD Greiner, JW AF Rogers, CJ Hance, KW Zaharoff, DA Perkins, SN Schlom, J Hursting, SD Greiner, JW TI Exercise enhances antigen specific immune responses in both systemic and mucosal compartments. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 4th Annual Conference on Frontiers in Cancer Prevention Research CY OCT 30-NOV 02, 2005 CL Baltimore, MD C1 Univ Texas, Austin, TX 78712 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 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 NOV PY 2005 VL 14 IS 11 SU S BP 2747S EP 2747S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 985BN UT WOS:000233351200271 ER PT J AU Granville, CA Tsurutani, J Robertson, M Hollander, MC Linnoila, IR Steinberg, SM Dennis, PA AF Granville, CA Tsurutani, J Robertson, M Hollander, MC Linnoila, IR Steinberg, SM Dennis, PA TI Inhibition of tobacco carcinogen-induced lung tumorigenesis by rapamycin, an inhibitor of mTOR. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 4th Annual Conference on Frontiers in Cancer Prevention Research CY OCT 30-NOV 02, 2005 CL Baltimore, MD C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 NOV PY 2005 VL 14 IS 11 SU S BP 2748S EP 2748S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 985BN UT WOS:000233351200276 ER PT J AU Matthews, CP Young, MR Colburn, NH AF Matthews, CP Young, MR Colburn, NH TI Prevention of human papilloma virus (HPV) E7-driven tumorigenesis by dominant negative AP-1 (TAM67) appears to be mediated by Cox-2 repression. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 4th Annual Conference on Frontiers in Cancer Prevention Research CY OCT 30-NOV 02, 2005 CL Baltimore, MD C1 NCI, Gene Regulat Sect, LCP, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 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 NOV PY 2005 VL 14 IS 11 SU S BP 2748S EP 2749S PN 2 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 985BN UT WOS:000233351200277 ER PT J AU Lou, JR Xiao, Z Stauffer, S Fatima, N Conrads, T Veenstra, T Greenwald, P Ali, I AF Lou, JR Xiao, Z Stauffer, S Fatima, N Conrads, T Veenstra, T Greenwald, P Ali, I TI Identification of celecoxib-modulated proteomic targets in colon cancer cell line, HCT-116. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 4th Annual Conference on Frontiers in Cancer Prevention Research CY OCT 30-NOV 02, 2005 CL Baltimore, MD C1 NCI, Bethesda, MD 20892 USA. SAIC Frederick Inc, Frederick, MD USA. NR 0 TC 0 Z9 0 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 NOV PY 2005 VL 14 IS 11 SU S BP 2750S EP 2750S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 985BN UT WOS:000233351200283 ER PT J AU Wright, ME Virtamo, J Hartman, AM Pietinen, P Edwards, BK Taylor, PR Huttunen, JK Albanes, D AF Wright, ME Virtamo, J Hartman, AM Pietinen, P Edwards, BK Taylor, PR Huttunen, JK Albanes, D TI Effects of alpha-tocopherol and beta-carotene supplementation on upper aerodigestive tract cancers: Results from a large, randomized controlled trial. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 4th Annual Conference on Frontiers in Cancer Prevention Research CY OCT 30-NOV 02, 2005 CL Baltimore, MD C1 NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Rockville, MD USA. Natl Publ Hlth Inst, Dept Epidemiol & Hlth Promot, Helsinki, Finland. NCI, Div Canc Control & Populat Sci, NIH, DHHS, Rockville, MD USA. RI Albanes, Demetrius/B-9749-2015 NR 0 TC 0 Z9 0 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 NOV PY 2005 VL 14 IS 11 SU S BP 2751S EP 2751S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 985BN UT WOS:000233351200290 ER PT J AU Abnet, CC Qiao, YL Kamangar, F Dong, ZW Taylor, PR Mark, SD Fraumeni, JF Dawsey, SM AF Abnet, CC Qiao, YL Kamangar, F Dong, ZW Taylor, PR Mark, SD Fraumeni, JF Dawsey, SM TI Self-reported goiter is associated with a significantly increased risk of gastric adenocarcinoma in a large population-based Chinese cohort. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 4th Annual Conference on Frontiers in Cancer Prevention Research CY OCT 30-NOV 02, 2005 CL Baltimore, MD C1 NCI, Bethesda, MD 20892 USA. Chinese Acad Med Sci, Inst Canc, Beijing 100021, Peoples R China. RI Qiao, You-Lin/B-4139-2012 OI Qiao, You-Lin/0000-0001-6380-0871 NR 0 TC 0 Z9 0 U1 0 U2 1 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 NOV PY 2005 VL 14 IS 11 SU S BP 2753S EP 2753S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 985BN UT WOS:000233351200295 ER PT J AU Berndt, SI Huang, WY Welch, R Chanock, SJ Pinsky, P Weissfeld, JL Hayes, RB AF Berndt, SI Huang, WY Welch, R Chanock, SJ Pinsky, P Weissfeld, JL Hayes, RB TI Transforming growth factor beta 1 (TGF beta 1) polymorphisms and advanced colorectal adenoma. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 4th Annual Conference on Frontiers in Cancer Prevention Research CY OCT 30-NOV 02, 2005 CL Baltimore, MD C1 NCI, Bethesda, MD 20892 USA. SAIC, Frederick, MD USA. Univ Pittsburgh, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 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 NOV PY 2005 VL 14 IS 11 SU S BP 2756S EP 2756S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 985BN UT WOS:000233351200307 ER PT J AU Rogers, S Dowling, E Valle, CG Mikhail, IS Seminara, D AF Rogers, S Dowling, E Valle, CG Mikhail, IS Seminara, D TI The trends and developments in consortia as tools for genetic epidemiology research. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 4th Annual Conference on Frontiers in Cancer Prevention Research CY OCT 30-NOV 02, 2005 CL Baltimore, MD C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 NOV PY 2005 VL 14 IS 11 SU S BP 2757S EP 2757S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 985BN UT WOS:000233351200312 ER PT J AU Forman, MR Schuz, J AF Forman, MR Schuz, J TI Birthweight-for-gestational age and risk of childhood cancers: Identification of new high-risk groups in big, but not high-birthweight, first-born babies. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 4th Annual Conference on Frontiers in Cancer Prevention Research CY OCT 30-NOV 02, 2005 CL Baltimore, MD C1 NCI, Lab Biosyst & Canc, Ctr Canc Res, Bethesda, MD 20892 USA. Univ Mainz, D-6500 Mainz, Germany. Inst Canc Epidemiol, Copenhagen, Denmark. NR 0 TC 0 Z9 0 U1 0 U2 1 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 NOV PY 2005 VL 14 IS 11 SU S BP 2758S EP 2758S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 985BN UT WOS:000233351200317 ER PT J AU Weiss, JM Huang, WY Rinaldi, S Fears, TR Chatterjee, N Chia, D Crawford, ED Kaaks, R Hayes, RB AF Weiss, JM Huang, WY Rinaldi, S Fears, TR Chatterjee, N Chia, D Crawford, ED Kaaks, R Hayes, RB TI IGF-1 and IGFBP-3: Increased risk of prostate cancer among men in the prostate, lung, colorectal, and ovarian (PLCO) cancer screening trial. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 4th Annual Conference on Frontiers in Cancer Prevention Research CY OCT 30-NOV 02, 2005 CL Baltimore, MD C1 NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. Int Agcy Res Canc, F-69372 Lyon, France. Univ Calif Los Angeles, Immunogenet Ctr, Los Angeles, CA USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 1 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 NOV PY 2005 VL 14 IS 11 SU S BP 2759S EP 2760S PN 2 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 985BN UT WOS:000233351200322 ER PT J AU Steele, VE Grubbs, CJ Lubet, RA AF Steele, VE Grubbs, CJ Lubet, RA TI The EGFr inhibitor, Iressa, prevents methylnitrosourea (MNU)-induced mammary carcinogenesis in rats. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 4th Annual Conference on Frontiers in Cancer Prevention Research CY OCT 30-NOV 02, 2005 CL Baltimore, MD C1 NCI, Bethesda, MD 20892 USA. Univ Alabama, Birmingham, AL USA. NR 0 TC 0 Z9 0 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 NOV PY 2005 VL 14 IS 11 SU S BP 2760S EP 2760S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 985BN UT WOS:000233351200325 ER PT J AU Hayes, RB Pinsky, P Riley, T Prorok, P Andriole, GL Crawford, D AF Hayes, RB Pinsky, P Riley, T Prorok, P Andriole, GL Crawford, D TI Prostate cancer incidence following a negative screening exam. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 4th Annual Conference on Frontiers in Cancer Prevention Research CY OCT 30-NOV 02, 2005 CL Baltimore, MD C1 NCI, Bethesda, MD 20892 USA. Informat Management Syst, Rockville, MD USA. Washington Univ, St Louis, MO USA. Univ Colorado, Denver, CO 80202 USA. NR 0 TC 0 Z9 0 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 NOV PY 2005 VL 14 IS 11 SU S BP 2762S EP 2762S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 985BN UT WOS:000233351200334 ER PT J AU Freedman, AN AF Freedman, AN TI Issues in the development, evaluation, and application of cancer risk prediction models. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 4th Annual Conference on Frontiers in Cancer Prevention Research CY OCT 30-NOV 02, 2005 CL Baltimore, MD C1 NCI, Appl Res Program, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 NOV PY 2005 VL 14 IS 11 SU S BP 2764S EP 2764S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 985BN UT WOS:000233351200337 ER PT J AU Szabo, E AF Szabo, E TI To do or not to do: Considerations for agent selection for cancer prevention clinical trials. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 4th Annual Conference on Frontiers in Cancer Prevention Research CY OCT 30-NOV 02, 2005 CL Baltimore, MD C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 NOV PY 2005 VL 14 IS 11 SU S BP 2766S EP 2767S PN 2 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 985BN UT WOS:000233351200343 ER PT J AU Albini, A AF Albini, A TI Angioprevention: Antiangiogenesis in a chemopreventive setting. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 4th Annual Conference on Frontiers in Cancer Prevention Research CY OCT 30-NOV 02, 2005 CL Baltimore, MD C1 Natl Canc Inst, Genoa, Italy. NR 3 TC 0 Z9 0 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 NOV PY 2005 VL 14 IS 11 SU S BP 2779S EP 2780S PN 2 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 985BN UT WOS:000233351200370 ER PT J AU Kohn, EC Boyce, E Kwitkowski, V Corrado, C Alessandro, R Posadas, E AF Kohn, EC Boyce, E Kwitkowski, V Corrado, C Alessandro, R Posadas, E TI Genomic and proteomic applications to cancer signatures and antiangiogenic therapy. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 4th Annual Conference on Frontiers in Cancer Prevention Research CY OCT 30-NOV 02, 2005 CL Baltimore, MD C1 NCI, Bethesda, MD 20892 USA. Univ Palermo, Palermo, Italy. NR 0 TC 0 Z9 0 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 NOV PY 2005 VL 14 IS 11 SU S BP 2780S EP 2780S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 985BN UT WOS:000233351200371 ER PT J AU Chanock, SJ AF Chanock, SJ TI Strategies for candidate SNP and haplotype selection in association studies. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 4th Annual Conference on Frontiers in Cancer Prevention Research CY OCT 30-NOV 02, 2005 CL Baltimore, MD C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 NOV PY 2005 VL 14 IS 11 SU S BP 2782S EP 2783S PN 2 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 985BN UT WOS:000233351200378 ER PT J AU Thomas, G AF Thomas, G TI Selection of SNP for the genome wide search of prostate cancer susceptibility genes. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 4th Annual Conference on Frontiers in Cancer Prevention Research CY OCT 30-NOV 02, 2005 CL Baltimore, MD C1 NCI, Bethesda, MD 20892 USA. Fdn Jean Dausset CEPH, Paris, France. NR 0 TC 0 Z9 0 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 NOV PY 2005 VL 14 IS 11 SU S BP 2782S EP 2782S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 985BN UT WOS:000233351200377 ER PT J AU Meissner, HI AF Meissner, HI TI Trends and determinants of cancer screening uptake. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 4th Annual Conference on Frontiers in Cancer Prevention Research CY OCT 30-NOV 02, 2005 CL Baltimore, MD C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 NOV PY 2005 VL 14 IS 11 SU S BP 2787S EP 2788S PN 2 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 985BN UT WOS:000233351200393 ER PT J AU Hawk, E Viner, J AF Hawk, E Viner, J TI NSAIDs and COXIBs: The burden of proof. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 4th Annual Conference on Frontiers in Cancer Prevention Research CY OCT 30-NOV 02, 2005 CL Baltimore, MD C1 NCI, DCP, Bethesda, MD 20892 USA. NCI, OCTR, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 NOV PY 2005 VL 14 IS 11 SU S BP 2789S EP 2790S PN 2 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 985BN UT WOS:000233351200396 ER PT J AU Szabo, E AF Szabo, E TI Chemoprevention of lung cancer: What's next? SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 4th Annual Conference on Frontiers in Cancer Prevention Research CY OCT 30-NOV 02, 2005 CL Baltimore, MD C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 NOV PY 2005 VL 14 IS 11 SU S BP 2797S EP 2797S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 985BN UT WOS:000233351200412 ER PT J AU Hesse, BW AF Hesse, BW TI Harnessing the power of an intelligent health communication environment. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 4th Annual Conference on Frontiers in Cancer Prevention Research CY OCT 30-NOV 02, 2005 CL Baltimore, MD ID SYSTEMS; CARE C1 NCI, Rockville, MD USA. NR 12 TC 0 Z9 0 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 NOV PY 2005 VL 14 IS 11 SU S BP 2798S EP 2798S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 985BN UT WOS:000233351200414 ER PT J AU Dennis, PA AF Dennis, PA TI Targeting the PI3K/Akt/mTOR pathway for cancer prevention. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 4th Annual Conference on Frontiers in Cancer Prevention Research CY OCT 30-NOV 02, 2005 CL Baltimore, MD ID INHIBITION; RAPAMYCIN; NEOPLASIA C1 NCI, CCR, Bethesda, MD 20892 USA. NR 3 TC 0 Z9 0 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 NOV PY 2005 VL 14 IS 11 SU S BP 2800S EP 2801S PN 2 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 985BN UT WOS:000233351200419 ER PT J AU Travis, LB AF Travis, LB TI The epidemiology of second primary cancers. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 4th Annual Conference on Frontiers in Cancer Prevention Research CY OCT 30-NOV 02, 2005 CL Baltimore, MD C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 NOV PY 2005 VL 14 IS 11 SU S BP 2801S EP 2801S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 985BN UT WOS:000233351200420 ER PT J AU Yancik, R AF Yancik, R TI US demographic imperative: Implication for the science and practice of cancer prevention in older persons. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 4th Annual Conference on Frontiers in Cancer Prevention Research CY OCT 30-NOV 02, 2005 CL Baltimore, MD C1 NIA, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 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 NOV PY 2005 VL 14 IS 11 SU S BP 2808S EP 2808S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 985BN UT WOS:000233351200438 ER PT J AU Yancik, R AF Yancik, R TI Population aging and cancer: A cross-national concern SO CANCER JOURNAL LA English DT Article DE aging and cancer; population aging; cancer burden in older persons; cancer mortality; elderly ID BURDEN AB Although malignant tumors occur at all ages, cancer disproportionately strikes individuals in the age group 65 years and older, Data from the National Cancer Institute Surveillance, Epidemiology, and End Results Program for the most recent five-year period, 1998-2002, reveal that 56% of all newly diagnosed cancer patients and 71% of cancer deaths are in this age group. Median ages of cancer patients at death for the major tumors common to both males and females, all races (lung, colorectal, lymphoma, leukemia, pancreas, stomach, urinary bladder) range from 71 to 77 years. The median age for prostate cancer is 79 years; for ovarian and female breast cancer, the median age is 71 for each tumor. These cancer statistics when cast against the demographic changes occurring in the U.S. population take on urgency and importance for cancer treatment and care in our nation's health care system. The U.S. Census Bureau demographic projections indicate that the number of persons 65 years and older in the United States will double from the current estimate of 35 million persons to a projected 70 million by 2030. Barring any cancer prevention breakthroughs, the expansion of the aged population will likely increase the absolute number of older individuals diagnosed and treated for cancer in coming decades. The United States is not unique as an aging developed industrial nation with a high proportion of the cancer burden in the elderly. Other developed industrial countries have a potentiality for increased cancer incidence and mortality as their populations grow older. This paper, using U.S. Bureau of Census demographic projections and current age standardized death rates per 100,000 population (from Worldwide Cancer Mortality Statistics, Cancer Mondial, WHO, and the International Association for Research on Cancer) compares cancer in the elderly in Italy and the United States. Italy is demographically ranked as the oldest nation in the world. Dimensions of the cancer burden challenge ahead are inferred in the context of two countries with aging populations to underscore the possible increase that demographic factors may have on the magnitude of the cancer problem for older persons in the next 25 years. C1 NIA, Geriatr & Clin Gerontol Program, NIH, NDHHS, Bethesda, MD 20892 USA. RP Yancik, R (reprint author), NIA, Geriatr & Clin Gerontol Program, NIH, NDHHS, Gateway Bldg,Suite 3C307, Bethesda, MD 20892 USA. EM yancikr@nia.nih.gov NR 8 TC 164 Z9 167 U1 1 U2 12 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 NOV-DEC PY 2005 VL 11 IS 6 BP 437 EP 441 DI 10.1097/00130404-200511000-00002 PG 5 WC Oncology SC Oncology GA 000ID UT WOS:000234453600002 PM 16393477 ER PT J AU Murgo, AJ Espinoza-Delgado, I AF Murgo, AJ Espinoza-Delgado, I TI Development of novel anticancer agents in older patients: Pharmacokinetic, pharmacodynamic, and other considerations SO CANCER JOURNAL LA English DT Article DE cancer in the elderly; pharmacokinetics; pharmacodynamics; drug development; novel agents; immune function; dendritic cells ID ACUTE MYELOID-LEUKEMIA; CANCER-TREATMENT TRIALS; ELDERLY-PATIENTS; DENDRITIC CELLS; SERUM CREATININE; IMMUNE-RESPONSE; THERAPY; MIGRATION; NONADHERENCE; CHEMOTHERAPY AB The development of novel anticancer agents in older patients presents both challenges and unique opportunities. Intrapatient variability due to comorbid conditions and the use of multiple concomitant medications may overshadow other age-related differences in pharmacokinetics. The increasing interest in oral agents may be especially problematic in older patients who have difficulty with adherence, particularly if the oral agents are given in combination or according to complex schedules. Polypharmacy, chronic comorbid conditions, and impaired organ reserve in the elderly can lead to pharmacodynamic differences such as increased toxicity and, possibly, reduced efficacy. Hampered immune responsiveness is an important area warranting further research. The development of novel agents to treat older patients with cancer cannot be successfully accomplished without increasing the proportion of elderly patients entered into clinical trials. Furthermore, data obtained from studies in older patients may provide valuable information applicable to the development of novel agents in younger patients and to a better understanding of cancer biology and treatment in general. C1 NCI, NIH, Rockville, MD 20852 USA. NIA, NIH, Bethesda, MD 20892 USA. RP Murgo, AJ (reprint author), NCI, NIH, 6130 Execut Blvd,Suite 7131, Rockville, MD 20852 USA. EM murgoa@mail.nih.gov NR 50 TC 0 Z9 0 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 NOV-DEC PY 2005 VL 11 IS 6 BP 481 EP 487 DI 10.1097/00130404-200511000-00007 PG 7 WC Oncology SC Oncology GA 000ID UT WOS:000234453600007 PM 16393482 ER PT J AU Morin, PJ AF Morin, PJ TI Claudin proteins in human cancer: Promising new targets for diagnosis and therapy SO CANCER RESEARCH LA English DT Review ID CLOSTRIDIUM-PERFRINGENS ENTEROTOXIN; GENE-EXPRESSION PROFILES; TIGHT JUNCTION PROTEINS; OVARIAN-CANCER; PANCREATIC-CANCER; SERIAL ANALYSIS; HEPATOCELLULAR-CARCINOMA; BREAST-CARCINOMA; BARRIER FUNCTION; CYCLIC-AMP AB The tight junction proteins claudins are abnormally regulated in several human cancers. In particular, claudin-3 and claudin-4 are frequently overexpressed in several neoplasias, including ovarian, breast, pancreatic, and prostate cancers. Although the exact roles of these proteins in tumorigenesis are still being uncovered, it is clear that they represent promising targets for cancer detection, diagnosis, and therapy. C1 NIA, Cellular & Mol Biol Lab, NIH, Baltimore, MD 21224 USA. RP Morin, PJ (reprint author), NIA, Cellular & Mol Biol Lab, NIH, Box 12,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM Morinp@grc.nia.nih.gov NR 50 TC 315 Z9 328 U1 1 U2 26 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 NOV 1 PY 2005 VL 65 IS 21 BP 9603 EP 9606 DI 10.1158/0008-5472.CAN-05-2782 PG 4 WC Oncology SC Oncology GA 979TF UT WOS:000232967000001 PM 16266975 ER PT J AU Amornphimoltham, P Patel, V Sodhi, A Nikitakis, NG Sauk, JJ Sausville, EA Molinolo, AA Gutkind, JS AF Amornphimoltham, P Patel, V Sodhi, A Nikitakis, NG Sauk, JJ Sausville, EA Molinolo, AA Gutkind, JS TI Mammalian target of rapamycin, a molecular target in squamous cell carcinomas of the head and neck SO CANCER RESEARCH LA English DT Article ID GROWTH-FACTOR RECEPTOR; HUMAN TUMOR XENOGRAFTS; SIGNALING PATHWAY; ANTITUMOR-ACTIVITY; CANCER-THERAPY; MTOR; INHIBITORS; SURVIVAL; KINASE; GENE AB Emerging knowledge on how the dysregulated function of signaling networks contributes to the malignant growth of squamous cell carcinoma of the head and neck (HNSCC) can now be exploited to identify novel mechanism-based anticancer treatments. In this regard, we have observed that persistent activation of the serine/threonine kinase Akt is a frequent event in HNSCC, and that blockade of its upstream kinase, 3'-phosphoinositide-dependent kinase 1, potently inhibits tumor cell growth. Akt promotes cell proliferation by its ability to coordinate mitogenic signaling with energy- and nutrient-sensing pathways that control protein synthesis through the atypical serine/threonine kinase, mammalian target of rapamycin (mTOR). This kinase, in turn, phosphorylates key eukaryotic translation regulators, including p70-S6 kinase and the eukaryotic translation initiation factor, 4E binding protein 1. Indeed, we show here that aberrant accumulation of the phosphorylated active form of S6, the most downstream target of the Akt-mTOR-p70-S6 kinase pathway, is a frequent event in clinical specimens from patients with HNSCC and their derived cell lines. Of interest, this enhanced level of the phosphorylated active form of S6 was rapidly reduced in HNSCC cell lines and HNSCC xenograft models at clinically relevant doses of rapamycin, which specifically inhibits mTOR. Furthermore, we observed that rapamycin displays a potent antitumor effect in vivo, as it inhibits DNA synthesis and induces the apoptotic death of HNSCC cells, ultimately resulting in tumor regression. These findings identify the Akt-mTOR pathway as a potential therapeutic target for HNSCC, and may provide the rationale for the early clinical evaluation of rapamycin and its analogues in patients with HNSCC. C1 Natl Inst Dent & Craniofacial Res, NIH, Oral & Pharyngeal Canc Branch, Bethesda, MD 20892 USA. Univ Maryland, Dept Diagnost Sci & Pathol, Sch Dent, Baltimore, MD 21201 USA. Univ Maryland, Greenebaum Canc Ctr, Baltimore, MD 21201 USA. RP Gutkind, JS (reprint author), Natl Inst Dent & Craniofacial Res, NIH, Oral & Pharyngeal Canc Branch, Bldg 30,Room 212,Convent Dr, Bethesda, MD 20892 USA. EM sg39v@nih.gov RI Gutkind, J. Silvio/A-1053-2009 NR 60 TC 145 Z9 149 U1 0 U2 7 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 NOV 1 PY 2005 VL 65 IS 21 BP 9953 EP 9961 DI 10.1158/0008-5472.CAN-05-0921 PG 9 WC Oncology SC Oncology GA 979TF UT WOS:000232967000046 PM 16267020 ER PT J AU Guo, ZS Naik, A O'Malley, ME Popovic, P Demarco, R Hu, Y Yin, XY Yang, ST Zeh, HJ Moss, B Lotze, MT Bartlett, DL AF Guo, ZS Naik, A O'Malley, ME Popovic, P Demarco, R Hu, Y Yin, XY Yang, ST Zeh, HJ Moss, B Lotze, MT Bartlett, DL TI The enhanced tumor selectivity of an oncolytic vaccinia lacking the host range and antiapoptosis genes SPI-1 and SPI-2 SO CANCER RESEARCH LA English DT Article ID SERINE PROTEASE INHIBITOR; VIRUS-INFECTED CELLS; RABBITPOX VIRUS; CANCER-THERAPY; B13R SPI-2; APOPTOSIS; DEATH; MECHANISM; POXVIRUS; VIROTHERAPY AB The ability of cancer cells to evade apoptosis may permit survival of a recombinant vaccinia lacking antiapoptotic genes in cancer cells compared with normal cells. We have explored the deletion of two vaccinia virus host range/ antiapoptosis genes, SPI-1 and SPI-2, for their effects on the viral replication and their ability to induce cell death in infected normal and transformed cells in vitro. Indeed, in three paired normal and transformed cell types, the SPI-1 and SPI-2 gene-deleted virus (vSP) preferentially replicates in transformed cells or p53-null cells when compared with their normal counterparts. This selectivity may be derived from the fact that vSP-infected normal cells died faster than infected cancer cells. A fraction of infected cells died with evidence of necrosis as shown by both flow cytometry and detection of high-mobility group B1 protein released from necrotic cells into the culture supernatant. When administered to animals, vSP retains full ability to replicate in tumor tissues, whereas replication in normal tissues is greatly diminished. In a model of viral pathogenesis, mice treated with vSP survived substantially longer when compared with mice treated with the wild-type virus. The mutant virus vSP displayed significant antitumoral effects in an MC38 s.c. tumor model in both nude (P < 0.001) and immunocompetent mice (P < 0.05). We conclude that this recombinant vaccinia vSP shows promise for oncolytic virus therapy. Given its enhanced tumor selectivity, improved safety profile, and substantial oncolytic effects following systemic delivery in murine models, it should also serve as a useful vector for tumor-directed gene therapy. C1 Univ Pittsburgh, Div Surg Oncol, Inst Canc, Pittsburgh, PA 15232 USA. Univ Pittsburgh, Sch Med, Dept Surg, Pittsburgh, PA 15232 USA. Univ Pittsburgh, Inst Mol Med, Pittsburgh, PA 15232 USA. NCI, Surg Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. Sun Yat Sen Univ, Affiliated Hosp 1, Dept Hepatobiliary Surg, Guangzhou, Guangdong, Peoples R China. RP Bartlett, DL (reprint author), Univ Pittsburgh, Div Surg Oncol, Inst Canc, Room 460,Canc Pavil,5150 Ctr Ave, Pittsburgh, PA 15232 USA. EM guozs@upmc.edu FU NCI NIH HHS [CA 100415] NR 52 TC 64 Z9 65 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 NOV 1 PY 2005 VL 65 IS 21 BP 9991 EP 9998 DI 10.1158/0008-5472.CAN-05-1630 PG 8 WC Oncology SC Oncology GA 979TF UT WOS:000232967000050 PM 16267024 ER PT J AU Kaldis, P Aleem, E AF Kaldis, P Aleem, E TI Cell cycle sibling rivalry - Cdc2 vs. Cdk2 SO CELL CYCLE LA English DT Article DE cyclin-dependent kinase; knockout mice; Cdk2; Cdc2; p27; cyclin E ID SKIN TUMOR-DEVELOPMENT; GROWTH-FACTOR-BETA; DEPENDENT KINASES; TARGETED DISRUPTION; PROTEIN-KINASE; MICE LACKING; P27(KIP1); INHIBITOR; P27; PHOSPHORYLATION AB It has been long believed that the cyclin-dependent kinase 2 (Cdk2) binds to cyclin E or cyclin A and exclusively promotes the G(1)/S phase transition and that Cdc2/cyclin B complexes play a major role in mitosis. We now provide evidence that Cdc2 binds to cyclin E ( in addition to cyclin A and B) and is able to promote the G(1)/S transition. This new concept indicates that both Cdk2 and/or Cdc2 can drive cells through G(1)/S phase in parallel. In this review we discuss the classic cell cycle model and how results from knockout mice provide new evidence that refute this model. We focus on the roles of Cdc2 and p27 in regulating the mammalian cell cycle and propose a new model for cell cycle regulation that accommodates these novel findings. C1 NCI, Mouse Canc Genet Program, NCI Frederick, Frederick, MD 21702 USA. RP Kaldis, P (reprint author), NCI, Mouse Canc Genet Program, NCI Frederick, Bldg 560-22-56,1050 Boyles St, Frederick, MD 21702 USA. EM kaldis@ncifcrf.gov RI Kaldis, Philipp/G-2714-2010; OI Kaldis, Philipp/0000-0002-7247-7591; Aleem, Eiman/0000-0002-9215-8213 FU Intramural NIH HHS NR 44 TC 57 Z9 60 U1 1 U2 3 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD NOV PY 2005 VL 4 IS 11 BP 1491 EP 1494 PG 4 WC Cell Biology SC Cell Biology GA 990OB UT WOS:000233752000008 PM 16258277 ER PT J AU Budhu, AS Wang, XW AF Budhu, AS Wang, XW TI Loading and unloading - Orchestrating centrosome duplication and spindle assembly by Ran/Crm1 SO CELL CYCLE LA English DT Article DE nucleophosmin; Crm1; Ran; mitosis; centrosome; hepatocellular carcinoma; liver cancer ID CELL-CYCLE CHECKPOINT; ACUTE MYELOGENOUS LEUKEMIA; NUCLEAR EXPORT SIGNAL; VIRUS-X PROTEIN; CHROMOSOME INSTABILITY; MAMMALIAN-CELLS; NUCLEOPHOSMIN; CANCER; P53; GADD45 AB The cell cycle is an intricate process of DNA replication and cell division that concludes with the formation of two genetically equivalent daughter cells. In this progression, the centrosome is duplicated once and only once during the G(1)/S transition to produce the bipolar spindle and ensure proper chromosome segregation. The presence of multiple centrosomes in cancer cells suggests that this process is mis-regulated during carcinogenesis. This suggests that certain factors exist that license the progression of centrosome duplication and serve to inhibit further duplications during a single cell cycle. Recent studies suggest that the Ran/Crm1 complex not only regulates nucleocytoplasmic transport but is also independently involved in mitotic spindle assembly. Factors that are capable of interacting with Ran/Crm1 through their nuclear export sequences, such as cyclins/ cdks, p53 and Brca1/2, may potentially function as centrosome checkpoints akin to the G(1)/S and G(2)/M checkpoints of the cell cycle. Our recent findings indicate that nucleophosmin, a protein whose trafficking is mediated by the Ran/Crm1 network, is one of such checkpoint factors for maintaining proper centrosome duplication. We propose that Ran/Crm1 may act as a 'loading dock' to coordinate various checkpoint factors in regulating the fidelity of centrosome duplication during cell cycle progression, and the disruption of these processes may lead to genomic instability and an acceleration of oncogenesis. C1 NCI, Liver Carcinogenesis Sect, Human Carcinogenesis Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Wang, XW (reprint author), NCI, Liver Carcinogenesis Sect, Human Carcinogenesis Lab, Ctr Canc Res,NIH, 37 Convent Dr,MSC 4255,Bldg 37, Bethesda, MD 20892 USA. EM xw3u@nih.gov RI Wang, Xin/B-6162-2009 FU NCI NIH HHS [Z01 BC005793-11] NR 49 TC 25 Z9 26 U1 0 U2 1 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD NOV PY 2005 VL 4 IS 11 BP 1510 EP 1514 PG 5 WC Cell Biology SC Cell Biology GA 990OB UT WOS:000233752000013 PM 16294017 ER PT J AU Zhuang, ZP Devouassoux-Shisheboran, M Lubensky, IA Tavassoli, F Vortmeyer, AO AF Zhuang, ZP Devouassoux-Shisheboran, M Lubensky, IA Tavassoli, F Vortmeyer, AO TI Premeiotic origin of teratomas - Is meiosis required for differentiation into mature tissues? SO CELL CYCLE LA English DT Article DE meiosis; tissue differentiation; teratoma; germ cell; immature teratoma; homozygosity; heterozygosity ID BENIGN OVARIAN TERATOMAS; MICRODISSECTION; GENETICS; BIOLOGY; MOUSE AB By virtue of meiotic cell division, primordial germ cells with heterozygous alleles develop into postmeiotic germ cells with homozygous alleles. Female and male germ cells may develop tumors - so-called teratomas - with a unique coexistence of a variety of histological elements from all three embryonic germ layers. 1,2 In particular, mature teratomas consist exclusively of developmentally mature tissues whereas immature teratomas contain variable amounts of mature and immature tissues. In this study, we report genetic analysis of individual tissue components from mature and immature teratomas. The majority of mature teratomas showed consistent and concordant homozygous alleles in all selectively procured tissue components. In a small subset of mature teratomas, we observed discordant homozygous alleles. In contrast, immature teratomatous tissue revealed a heterozygous genotype. Remarkably, mature tissue components within immature teratoma revealed homozygosity. The findings suggest that immature teratomas and at least a subset of mature teratomas may originate from premeiotic cells, and implicate that meiosis may be required for differentiation into mature tissues. C1 NINDS, NIH, Bethesda, MD 20892 USA. INSERM, F-69008 Lyon, France. Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06510 USA. RP Vortmeyer, AO (reprint author), NINDS, NIH, Bldg 10,Room 5D37, Bethesda, MD 20892 USA. EM vortmeyera@mail.nih.gov FU Intramural NIH HHS NR 15 TC 5 Z9 5 U1 1 U2 2 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD NOV PY 2005 VL 4 IS 11 BP 1683 EP 1687 PG 5 WC Cell Biology SC Cell Biology GA 990OB UT WOS:000233752000033 PM 16258281 ER PT J AU Dougherty, GW Adler, HJ Rzadzinska, A Gimona, M Tomita, Y Lattig, MC Merritt, RC Kachar, B AF Dougherty, GW Adler, HJ Rzadzinska, A Gimona, M Tomita, Y Lattig, MC Merritt, RC Kachar, B TI CLAMP, a novel microtubule-associated protein with EB-type calponin homology SO CELL MOTILITY AND THE CYTOSKELETON LA English DT Article DE microtubule-associated protein; cytoskeleton; pillar cells; tubulin ID GUINEA-PIG ORGAN; COCHLEAR EPITHELIAL-CELLS; COLD STABILITY; SUPPORTING CELLS; BINDING DOMAIN; POSTTRANSLATIONAL MODIFICATIONS; FUNCTIONAL DOMAINS; SENSORY EPITHELIUM; FAMILY PROTEINS; ACTIN-BINDING AB Microtubules (MTs) are polymers of a and P tubulin dimers that mediate many cellular functions, including the establishment and maintenance of cell shape. The dynamic properties of MTs may be influenced by tubulin isotype, posttranslational modifications of tubulin, and interaction with microtubule-associated proteins (MAPs). End-binding (EB) family proteins affect MT dynamics by stabilizing MTs, and are the only MAPs reported that bind MTs via a calponin-homology (CH) domain (J Biol Chem 278 (2003) 49721-49731; J Cell Biol 149 (2000) 761766). Here, we describe a novel 27 kDa protein identified from an inner ear organ of Corti library. Structural homology modeling demonstrates a CH domain in this protein similar to EB proteins. Northern and Western blottings confirmed expression of this gene in other tissues, including brain, lung, and testis. In the organ of Corti, this protein localized throughout distinctively large and well-ordered NIT bundles that support the elongated body of mechanically stiff pillar cells of the auditory sensory epithelium. When ectopically expressed in Cos-7 cells, this protein localized along cytoplasmic MTs, promoted NIT bundling, and efficiently stabilized MTs against depolymerization in response to high concentration of nocodazole and cold temperature. We propose that this protein, designated CLAMP, is a novel MAP and represents a new member of the CH domain protein family. C1 NIDCD, Sect Struct Cell Biol, NIH, Bethesda, MD 20892 USA. Ist Ric Farmacol Mario Negri, Consorzio Mario Negri Sud, Dept Cell Biol & Oncol, I-66030 Santa Maria Imbaro, Chieti, Italy. Georgetown Univ, Lombardi Canc Ctr, Washington, DC 20057 USA. NINDS, Sect G Prot Coupled Receptors, NIH, Bethesda, MD 20892 USA. RP Kachar, B (reprint author), NIDCD, Sect Struct Cell Biol, NIH, 50 South Dr,MSC 8027,Bldg 50,Room 4249, Bethesda, MD 20892 USA. EM kacharb@nidcd.nih.gov NR 67 TC 18 Z9 18 U1 0 U2 7 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0886-1544 J9 CELL MOTIL CYTOSKEL JI Cell Motil. Cytoskeleton PD NOV PY 2005 VL 62 IS 3 BP 141 EP 156 DI 10.1002/cm.20093 PG 16 WC Cell Biology SC Cell Biology GA 981GE UT WOS:000233074800002 PM 16206169 ER PT J AU Rzadzinska, A Schneider, M Noben-Trauth, K Bartles, JR Kachar, B AF Rzadzinska, A Schneider, M Noben-Trauth, K Bartles, JR Kachar, B TI Balanced levels of espin are critical for stereociliary growth and length maintenance SO CELL MOTILITY AND THE CYTOSKELETON LA English DT Article DE hair cells; actin; cytoskeleton; actin binding proteins; stereocilia renewal; hearing ID HAIR-CELLS; ACTIN-FILAMENTS; INNER-EAR; POSTNATAL-DEVELOPMENT; MOLECULAR TREADMILL; BUNDLING PROTEIN; HAMSTER COCHLEA; CUTICULAR PLATE; BIRD COCHLEA; JERKER MOUSE AB Hearing and balance depend on microvilli-like actin-based projections of sensory hair cells called stereocilia. Their sensitivity to mechanical displacements on the nanometer scale requires a highly organized hair bundle in which the physical dimension of each stereocilium is tightly controlled. The length and diameter of each stereocilium are established during hair bundle maturation and maintained by life-long continuing dynamic regulation. Here, we studied the role of the actin-bundling protein Espin in stereociliary growth by examining the hair cell stereocilia of Espin-deficient jerker mice (EspN(je)), and the effects of transiently over-expressing Espin in the neuroepithelial cells of the organ of Corti cultures. Using fluorescence scanning confocal and electron microscopy, we found that a lack of Espin results in inhibition of stereociliary growth followed by progressive degeneration of the hair bundle. In contrast, overexpression of Espin induced lengthening of stereocilia and microvilli that mirrored the elongation of the actin filament bundle at their core. Interestingly, Espin deficiency also appeared to influence the localization of Myosin XVa, an unconventional myosin that is normally present at the stereocilia tip at levels proportional to stereocilia length. These results indicate that Espin is important for the growth and maintenance of the actin-based protrusions of inner ear neuroepithelial cells. Cell Motil. C1 NIDCD, Sect Struct Cell Biol, NIH, Bethesda, MD 20892 USA. NIDCD, Neurogenet Sect, NIH, Rockville, MD USA. Northwestern Univ, Feinberg Sch Med, Dept Cell & Mol Biol, Chicago, IL 60611 USA. RP Kachar, B (reprint author), NIDCD, Sect Struct Cell Biol, NIH, Bldg 50,Rm 4249,50 South Dr, Bethesda, MD 20892 USA. EM kacharb@nidcd.nih.gov FU NIDCD NIH HHS [DC004314] NR 27 TC 43 Z9 44 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0886-1544 J9 CELL MOTIL CYTOSKEL JI Cell Motil. Cytoskeleton PD NOV PY 2005 VL 62 IS 3 BP 157 EP 165 DI 10.1002/cm.20094 PG 9 WC Cell Biology SC Cell Biology GA 981GE UT WOS:000233074800003 PM 16206170 ER PT J AU Yeung, ML Bennasser, Y Le, SY Jeang, KT AF Yeung, ML Bennasser, Y Le, SY Jeang, KT TI siRNA, miRNA and HIV: promises and challenges SO CELL RESEARCH LA English DT Review DE small interfering RNA; microRNA; RNA interference; human immunodeficiency virus type-1; RNA-induced silencing complex; suppressor of siRNA; viral miRNA ID VIRUS TYPE-1 REPLICATION; SMALL INTERFERING RNA; CAENORHABDITIS-ELEGANS; C-ELEGANS; MESSENGER-RNAS; MICRORNA GENES; HUMAN-CELLS; POSTTRANSCRIPTIONAL REGULATION; MEDIATED INHIBITION; ENCODED MICRORNAS AB Small interfering RNA (siRNA) and microRNA (miRNA) are small RNAs of 18-25 nucleotides (nt) in length that play important roles in regulating gene expression. They are incorporated into an RNA-induced silencing complex (RISC) and serve as guides for silencing their corresponding target mRNAs based on complementary base-pairing. The promise of gene silencing has led many researchers to consider siRNA as an anti-viral tool. However, in long-term settings, many viruses appear to escape from this therapeutical strategy. An example of this may be seen in the case of human immunodeficiency virus type-1 (HIV-1) which is able to evade RNA silencing by either mutating the siRNA-targeted sequence or by encoding for a partial suppressor of RNAi (RNA interference). On the other hand, because miRNA targeting does not require absolute complementarity of base-pairing, mutational escape by viruses from miRNA-specified silencing may be more difficult to achieve. In this review, we discuss stratagems used by various viruses to avoid the cells' antiviral si/mi-RNA defenses and notions of how viruses might control and regulate host cell genes by encoding viral miRNAs (vmiRNAs). C1 NIAID, Mol Virol Sect, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, Nanobiol Program, NIH, Frederick, MD 21702 USA. RP Jeang, KT (reprint author), Bldg 4,Room 306,9000 Rockville Pike, Bethesda, MD 20892 USA. EM kj7e@nih.gov RI Jeang, Kuan-Teh/A-2424-2008 NR 102 TC 45 Z9 52 U1 0 U2 8 PU INST BIOCHEMISTRY & CELL BIOLOGY PI SHANGHAI PA SIBS, CAS, 319 YUEYAND ROAD, SHANGHAI, 200031, PEOPLES R CHINA SN 1001-0602 J9 CELL RES JI Cell Res. PD NOV-DEC PY 2005 VL 15 IS 11-12 BP 935 EP 946 DI 10.1038/sj.cr.7290371 PG 12 WC Cell Biology SC Cell Biology GA 997XG UT WOS:000234281600021 PM 16354572 ER PT J AU Rezanka, LJ Kenny, JJ Longo, DL AF Rezanka, LJ Kenny, JJ Longo, DL TI Dual isotype expressing B cells [kappa(+)/lambda(+)] arise during the ontogeny of B cells in the bone marrow of normal nontransgenic mice SO CELLULAR IMMUNOLOGY LA English DT Article DE rodent; B cells; antibodies; autoantibodies; repertoire development ID INTERNATIONAL IMMUNOGENETICS DATABASE; REACTIVE LYMPHOCYTES-B; RECOMBINATION ACTIVATING GENES; IMMUNOGLOBULIN LIGHT-CHAINS; CLONAL DELETION; TRANSGENIC MICE; MARGINAL-ZONE; KAPPA-LIGHT; V(D)J RECOMBINATION; POSITIVE SELECTION AB Central to the clonal selection theory is the tenet that a single B cell expresses a single receptor with a single specificity. Previously, based on our work in anti-phosphocholine transgenic mouse models, we suggested that B cells escaped clonal deletion by coexpression of more than one receptor on their cell surface. We argued that '' receptor dilution '' was necessary when: (i) the expressed immunoglobulin receptor is essential for immune protection against pathogens and (ii) this protective receptor is autoreactive and would be clonally deleted, leaving a hole in the B cell repertoire. Here, we demonstrate that dual isotype expressing B cells arise during the normal ontogeny of B cells in the bone marrow and populate both the spleen and peritoneal cavity of nontransgenic mice. Furthermore, single cell analysis of the expressed immunoglobulin light chains suggests that receptor editing may play a role in the generation of a significant fraction of dual isotype expressing B cells. Published by Elsevier Inc. C1 NIA, Immunol Lab, NIH, Baltimore, MD 21224 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Rezanka, LJ (reprint author), NIA, Immunol Lab, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM rezankal@grc.nia.nih.gov FU Intramural NIH HHS NR 84 TC 13 Z9 13 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD NOV PY 2005 VL 238 IS 1 BP 38 EP 48 DI 10.1016/j.cellimm.2005.12.004 PG 11 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 021NV UT WOS:000235990800005 PM 16458869 ER PT J AU Barillas-Mury, C Kumar, S AF Barillas-Mury, C Kumar, S TI Plasmodium-mosquito interactions: a tale of dangerous liaisons SO CELLULAR MICROBIOLOGY LA English DT Review ID MALARIA PARASITE DEVELOPMENT; VECTOR ANOPHELES-GAMBIAE; TIME BOMB MODEL; MIDGUT CELLS; CIRCUMSPOROZOITE PROTEIN; OOKINETE INVASION; SALIVARY-GLAND; SPOROGONIC DEVELOPMENT; FUNCTIONAL GENOMICS; AEDES-AEGYPTI AB To complete their life cycle, Plasmodium parasites must survive the environment in the insect host, cross multiple barriers including epithelial layers, and avoid destruction by the mosquito immune system. Completion of the Anopheles gambiae and Plasmodium falciparum genomes has opened the opportunity to apply high throughput methods to the analysis of gene function. The burst of information generated by these approaches and the use of molecular markers to investigate the cell biology of these interactions is broadening our understanding of this complex system. This review discusses our current understanding of the critical interactions that take place during the journey of Plasmodium through the mosquito host, with special emphasis on the responses of midgut epithelial cells to parasite invasion. C1 NIAID, Mosquito Immun & Vector Competence Unit, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. RP Barillas-Mury, C (reprint author), NIAID, Mosquito Immun & Vector Competence Unit, Lab Malaria & Vector Res, NIH, 12735 Twinbrook Pkwy, Rockville, MD 20852 USA. EM cbarillas@niaid.nih.gov NR 56 TC 22 Z9 23 U1 1 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1462-5814 J9 CELL MICROBIOL JI Cell Microbiol. PD NOV PY 2005 VL 7 IS 11 BP 1539 EP 1545 DI 10.1111/j.1462-5822.2005.00615.x PG 7 WC Cell Biology; Microbiology SC Cell Biology; Microbiology GA 971NP UT WOS:000232391500002 PM 16207241 ER PT J AU Myers, JN O'Neil, KM Walsh, TE Hoffmeister, KJ Venzon, DJ Johnson, BE AF Myers, JN O'Neil, KM Walsh, TE Hoffmeister, KJ Venzon, DJ Johnson, BE TI The pulmonary status of patients with limited-stage small cell lung cancer 15 years after treatment with chemotherapy and chest irradiation SO CHEST LA English DT Article DE lung cancer; oncology; pulmonary function test; radiology; toxicity ID LONG-TERM CHANGES; RADIATION-THERAPY; THORACIC RADIOTHERAPY; HODGKINS-DISEASE; FUNCTION TESTS; FOLLOW-UP; TOXICITY; SURVIVAL; INJURY; PNEUMONITIS AB Study objectives: To describe pulmonary symptoms, signs, pulmonary function, and lung imaging studies in patients with limited-stage small cell lung cancer (SCLC) 2 to 15 years after receiving treatment with chemotherapy and chest radiotherapy. Design: Retrospective review of clinical records and radiographic studies of patients treated in three different prospective combined-modality studies. Setting: Federal hospital. Patients: One hundred fifty-six patients with SCLC who were enrolled between 1974 and 1994. Interventions: Patients with limited-stage SCLC treated on prospective therapeutic studies of combined chemotherapy and radiation therapy were identified. Pulmonary symptoms, physical findings, pulmonary function tests, arterial blood gas measurements, and chest imaging studies were assessed at baseline, and at I to 2 years, at 3 to 5 years, and at > 5 years following the initiation of treatment. Measurements and results: Initial symptoms included cough in 84 (55%), dyspnea in 59 (39%), and sputum production in 26 (17%). Twenty-three patients lived beyond 5 years (15%) without evidence of recurrence. Seven of these 5-year survivors were without pulmonary symptoms. Pulmonary function test results showed no significant changes in percent predicted values for FVC, FEV1, and FEV1/FVC ratio over the time periods reviewed. The percent predicted values for the diffusing capacity of the lung for carbon monoxide decreased from 71% before the start of treatment to 56% (p < 0.032) at I to 2 years. Values improved in most patients beyond 5),Cars after starting treatment. Radiologist interpretations of chest imaging studies were available for 17 of 23 patients surviving > 5),cars. Most patients had minimal to no changes in imaging study findings beyond 5 years. Conclusions: Long-term survivors with limited-stage SCLC who were treated with combined chemotherapy and chest radiotherapy have minimal changes in pulmonary symptoms or function from 5 to 15 years after the start of treatment. A concern for late toxicity from combined-modality therapy should not dissuade clinicians from offering therapy with potentially curative result with minimal to no pulmonary dysfunction. C1 Uniformed Serv Univ Hlth Sci, Dept Med, Bethesda, MD 20814 USA. Natl Naval Med Res Inst, Div Pulm Crit Care, Div Hematol Oncol, Bethesda, MD USA. Montgomery Cty Dept Hlth, Bethesda, MD USA. NCI, Biostat & Data Management Sect, NIH, Bethesda, MD 20892 USA. USN, Med Branch, Bethesda, MD 20084 USA. Dana Farber Canc Inst, Dept Adult Oncol, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. RP Myers, JN (reprint author), Uniformed Serv Univ Hlth Sci, Dept Med, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM JMyers@usuhs.mil RI Venzon, David/B-3078-2008 NR 28 TC 5 Z9 6 U1 0 U2 1 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD NOV PY 2005 VL 128 IS 5 BP 3261 EP 3268 DI 10.1378/chest.128.5.3261 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 987HG UT WOS:000233508400026 PM 16304271 ER PT J AU van Erp, NPH Baker, SD Zhao, M Rudek, M Guchelaar, HJ Nortier, JWR Sparreboom, A Gelderblom, H AF van Erp, NPH Baker, SD Zhao, M Rudek, M Guchelaar, HJ Nortier, JWR Sparreboom, A Gelderblom, H TI Effect of milk thistle (Silybum marianum) on the pharmacokinetics of irinotecan SO CLINICAL CANCER RESEARCH LA English DT Article ID ST-JOHNS-WORT; COMPLEMENTARY/ALTERNATIVE MEDICINE; HERBAL REMEDIES; HEALTH-RISKS; CANCER; METABOLISM; SILYMARIN; INDINAVIR; PREVALENCE; FLAVONOIDS AB Purpose: Milk thistle (Silybum marianum) is one of the most commonly used herbal therapies, and its principal constituent silybin significantly inhibits cytochrome P450 isoform 3A4 (CYP3A4) and UDP glucuronosyltransferase isoform 1A1 (UGT1A1) in vitro. Here, we investigated whether milk thistle affects the pharmacokinetics of irinotecan, a substrate for CYP3A4 and UGT1A1, in humans. Experimental Design: Six cancer patients were treated with irinotecan (dose, 125 mg/m 2) given as a 90-minute infusion once every week. Four days before the second dose, patients received 200 mg milk thistle, thrice a day, for 14 consecutive days. Pharmacokinetic studies of irinotecan and its metabolites 7-ethyl-10-hydroxycamptothecin (SN-38), 7-ethyl-10-[3,4,5-trihydroxy-pyran-2-carboxylic acid]-camptothecin (SN-38-glucuronide), and 7-ethyl-10-[4-N(5-aminopentanoic acid)-1-piperidino]-carbonyloxycamptothecin were done during the first three irinotecan administrations. Results: Short-term (4 days) or more prolonged intake of milk thistle (12 days) had no significant effect on irinotecan clearance (mean, 31.2 versus 25.4 versus 25.6 L/h; P = 0.16). The area under the curve ratio of SN-38 and irinotecan was slightly decreased by milk thistle (2.58% versus 2.23% versus 2.17%; P = 0.047), whereas the relative extent of glucuroniclation of SN-38 was similar (10.8 versus 13.5 versus 13.1; P = 0.64). Likewise, the area under the curve ratio of 7-ethyl-10-[4-N-(5-aminopentanoic acid)-1-peridino]-carbonyloxycamptothecin and irinotecan was unaffected by milk thistle (0.332 versus 0.285 versus 0.337; P = 0.53). The maximum plasma concentrations of silybin ranged between 0.0249 and 0.257 mu mol/L. Conclusions: Silybin concentrations after intake of milk thistle are too low to significantly affect the function of CYP3A4 and UGT1A1 in vivo, indicating that milk thistle is unlikely to alter the disposition of anticancer drugs metabolized by these enzymes. C1 Johns Hospkins, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21231 USA. Leiden Univ, Med Ctr, Dept Clin Pharm & Toxicol, Leiden, Netherlands. Leiden Univ, Med Ctr, Dept Clin Oncol, Leiden, Netherlands. Natl Canc Inst, Clin Pharmacol Res Core, Bethesda, MD USA. RP Baker, SD (reprint author), Johns Hospkins, Sidney Kimmel Comprehens Canc Ctr, Room 1M87,Bunting Blaustein Canc Res Bldg,1650 Or, Baltimore, MD 21231 USA. EM sbaker7@jhmi.edu RI Sparreboom, Alex/B-3247-2008; van Erp, Nielka/A-1907-2016 FU NCCIH NIH HHS [P50 AT00437]; NCI NIH HHS [P30 CA069773] NR 37 TC 67 Z9 70 U1 2 U2 11 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 NOV 1 PY 2005 VL 11 IS 21 BP 7800 EP 7806 DI 10.1158/1078-0432.CCR-05-1288 PG 7 WC Oncology SC Oncology GA 984VC UT WOS:000233331400029 PM 16278402 ER PT J AU McNeel, DG Eickhoff, J Lee, FT King, DM Alberti, D Thomas, JP Friedl, A Kolesar, J Marnocha, R Volkman, J Zhang, JL Hammershaimb, L Zwiebel, JA Wilding, G AF McNeel, DG Eickhoff, J Lee, FT King, DM Alberti, D Thomas, JP Friedl, A Kolesar, J Marnocha, R Volkman, J Zhang, JL Hammershaimb, L Zwiebel, JA Wilding, G TI Phase I trial of a monoclonal antibody specific for alpha(v)beta(3) integrin (MEDI-522) in patients with advanced malignancies, including an assessment of effect on tumor perfusion SO CLINICAL CANCER RESEARCH LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; VASCULAR INTEGRIN ALPHA(V)BETA(3); CELL LUNG-CANCER; COLORECTAL-CANCER; BREAST-CANCER; HUMAN KIDNEY; BEVACIZUMAB; ANGIOGENESIS; VITAXIN; INHIBITOR AB At present, a variety of agents targeting tumor angiogenesis are under clinical investigation as new therapies for patients with cancer. Overexpression of the 003 integrin on tumor vasculature has been associated with an aggressive phenotype of several solid tumor types. Murine models have shown that antibodies targeting the U,133 integrin can affect tumor vasculature and block tumor formation and metastasis. These findings suggest that antibodies directed at alpha(v)beta(3) could be investigated in the treatment of human malignancies. The current phase I dose escalation study evaluated the safety of MEDI-522, a monoclonal antibody specific for the alpha(v)beta(3) integrin, in patients with advanced malignancies. Twenty-five patients with a variety of metastatic solid tumors were treated with MEDI-522 on a weekly basis with doses ranging from 2 to 10 mg/kg/wk. Adverse events were assessed weekly; pharmacokinetic studies were done; and radiographic staging was done every 8 weeks. In addition, dynamic computed tomography imaging was done at baseline and at 8 weeks in patients with suitable target lesions amenable to analysis, to potentially identify the effect of MEDI-522 on tumor perfusion. Treatment was well tolerated, and a maximum tolerated dose was not identified by traditional dose-limiting toxicities. The major adverse events observed were grade 1 and 2 infusion-related reactions (fever, rigors, flushing, injection site reactions, and tachycardia), low-grade constitutional and gastrointestinal symptoms (fatigue, myalgias, and nausea), and asymptomatic hypophosphatemia. Dynamic computed tomography imaging suggested a possible effect on tumor perfusion with an increase in contrast mean transit time from baseline to the 8-week evaluation with increasing doses of MEDI-522. No complete or partial responses were observed. Three patients with metastatic renal cell cancer experienced prolonged stable disease (34 weeks, > 1 and > 2 years) on treatment. With this weekly schedule of administration, and in the doses studied, MEDI-522 seems to be without significant toxicity, may have effects on tumor perfusion, and may have clinical activity in renal cell cancer. These findings suggest the MEDI-522 could be further investigated as an antiangiogenic agent for the treatment of cancer. C1 Univ Wisconsin, Ctr Comprehens Canc, Dept Med, Madison, WI 53792 USA. Univ Wisconsin, Ctr Comprehens Canc, Dept Biostat, Madison, WI 53792 USA. Univ Wisconsin, Ctr Comprehens Canc, Dept Radiol, Madison, WI 53792 USA. Univ Wisconsin, Ctr Comprehens Canc, Dept Pathol, Madison, WI 53792 USA. Univ Wisconsin, Ctr Comprehens Canc, Sch Pharm, Madison, WI 53792 USA. MedImmune Oncol Inc, Gaithersburg, MD USA. NCI, Invest Drug Branch, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. RP McNeel, DG (reprint author), Univ Wisconsin, Ctr Comprehens Canc, Dept Med, K4-518 Clin Sci Ctr,600 Highland Ave, Madison, WI 53792 USA. EM dm3@medicine.wisc.edu FU NCI NIH HHS [N02-CO-124001, U01 CA62491, U01 CA062491]; NCRR NIH HHS [M01 RR03186] NR 31 TC 86 Z9 94 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 NOV 1 PY 2005 VL 11 IS 21 BP 7851 EP 7860 DI 10.1158/1078-0432.CCR-05-0262 PG 10 WC Oncology SC Oncology GA 984VC UT WOS:000233331400035 PM 16278408 ER PT J AU Freidlin, B Simon, R AF Freidlin, B Simon, R TI Adaptive signature design: An adaptive clinical trial design for generating and prospectively testing a gene expression signature for sensitive patients SO CLINICAL CANCER RESEARCH LA English DT Article ID GROWTH-FACTOR RECEPTOR; B-CELL LYMPHOMA; CANCER; SURVIVAL AB Purpose: A new generation of molecularly targeted agents is entering the definitive stage of clinical evaluation. Many of these drugs benefit only a subset of treated patients and may be overlooked by the traditional, broad-eligibility approach to randomized clinical trials. Thus, there is a need for development of novel statistical methodology for rapid evaluation of these agents. Experimental Design: We propose a new adaptive design for randomized clinical trials of targeted agents in settings where an assay or signature that identifies sensitive patients is not available at the outset of the study. The design combines prospective development of a gene expression-based classifier to select sensitive patients with a properly powered test for overall effect. Results: Performance of the adaptive design, relative to the more traditional design, is evaluated in a simulation study. It is shown that when the proportion of patients sensitive to the new drug is low, the adaptive design substantially reduces the chance of false rejection of effective new treatments. When the new treatment is broadly effective, the adaptive design has power to detect the overall effect similar to the traditional design. Formulas are provided to determine the situations in which the new design is advantageous. Conclusion: Development of a gene expression-based classifier to identify the subset of sensitive patients can be prospectively incorporated into a randomized phase III design without compromising the ability to detect an overall effect. C1 NCI, Div Canc Treatment & Diganost, Biomet Res Branch, Bethesda, MD 20892 USA. RP Freidlin, B (reprint author), NCI, Div Canc Treatment & Diganost, Biomet Res Branch, 6130 Execut Blvd,EPN 8122,MSC 7434, Bethesda, MD 20892 USA. EM freidlinb@ctep.nci.nih.gov NR 16 TC 159 Z9 163 U1 1 U2 8 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 NOV 1 PY 2005 VL 11 IS 21 BP 7872 EP 7878 DI 10.1158/1078-0432.CCR-05-0605 PG 7 WC Oncology SC Oncology GA 984VC UT WOS:000233331400038 PM 16278411 ER PT J AU Vallera, DA Brechbiel, MW Burns, LJ Panoskaltsis-Mortari, A Dusenbery, KE Clohisy, DR Vitetta, ES AF Vallera, DA Brechbiel, MW Burns, LJ Panoskaltsis-Mortari, A Dusenbery, KE Clohisy, DR Vitetta, ES TI Radioimmunotherapy of CD22-expressing Daudi tumors in nude mice with a Y-90-labeled anti-CD22 monoclonal antibody SO CLINICAL CANCER RESEARCH LA English DT Article ID NON-HODGKINS-LYMPHOMA; B-CELL LYMPHOMA; CHAIN-CONTAINING IMMUNOTOXINS; ANTIGEN RECEPTOR; IN-VITRO; IDEC-Y2B8 RADIOIMMUNOTHERAPY; RECOMBINANT IMMUNOTOXIN; IBRITUMOMAB TIUXETAN; CD22-DEFICIENT MICE; INVIVO THERAPY AB A study was undertaken to investigate the efficacy of a high affinity, rapidly internalizing anti-CD22 monoclonal antibody for selectively delivering high-energy Y-90 radioactivity to B lymphoma cells in vivo. The antibody, RFB4, was readily labeled with Y-90 using the highly stable chelate, 1B4M-diethylenetriaminepentaacetic acid. Labeled RFB4 selectively bound to the CD22(+) Burkitt's lymphoma cell line Daudi, but not to CD22(-) control cells in vitro as compared with a control antibody, and was more significantly bound (P = 0.03) to Daudi solid tumors growing in athymic nude mice. Biodistribution data correlated well with the antitumor effect. The therapeutic effect of Y-90-labeled anti-CD22 (Y22) was dose-dependent, irreversible, and the best results were achieved in mice receiving a single i.p. dose of 196 mu Ci. These mice displayed a significantly better (P < 0.01) antitumor response than control mice and survived > 200 days with no evidence of tumor. Histology studies showed no significant injury to kidney, liver, or small intestine. Importantly, tumor-bearing mice treated with Y22 had no radiologic bone marrow damage compared with tumor-bearing mice treated with the control-labeled antibody arguing that the presence of CD22(+) tumor protected mice from bone marrow damage. When anti-CD22 radioimmunotherapy was compared to radioimmunotherapy with anti-CD19 and anti-CD45 antibodies, all three antibodies distributed significantly high levels of radioisotope to flank tumors in vivo compared with controls (P < 0.05), induced complete remission, and produced long-term, tumor-free survivors. These findings indicate that anti-CD22 radioimmunotherapy with Y22 is highly effective in vivo against CD22-expressing malignancies and may be a useful therapy for drug-refractory B cell leukemia patients. C1 Univ Minnesota, Ctr Canc, Dept Therapeut Radiol Radiat Oncol, Minneapolis, MN 55455 USA. Univ Minnesota, Ctr Canc, Dept Med, Minneapolis, MN 55455 USA. Univ Minnesota, Ctr Canc, Dept Pediat, Minneapolis, MN 55455 USA. Univ Minnesota, Ctr Canc, Dept Orthoped Surg, Minneapolis, MN 55455 USA. NCI, Radiat Oncol Branch, Radioimmune & Inorgan Chem Sect, Bethesda, MD 20892 USA. Univ Texas, SW Med Ctr, Ctr Canc Immunobiol, Dallas, TX 75230 USA. RP Vallera, DA (reprint author), Univ Minnesota, Ctr Canc, Dept Therapeut Radiol Radiat Oncol, MMC 367, Minneapolis, MN 55455 USA. EM valle001@umn.edu FU NCI NIH HHS [R01-CA36725] NR 55 TC 7 Z9 10 U1 0 U2 1 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 NOV 1 PY 2005 VL 11 IS 21 BP 7920 EP 7928 DI 10.1158/1078-0432.CCR-05-0725 PG 9 WC Oncology SC Oncology GA 984VC UT WOS:000233331400044 PM 16278417 ER PT J AU Dowlati, A Robertson, K Radivoyevitch, T Waas, J Ziats, NP Hartman, P Abdul-Karim, FW Wasman, JK Jesberger, J Lewin, J McCrae, K Ivy, P Remick, SC AF Dowlati, A Robertson, K Radivoyevitch, T Waas, J Ziats, NP Hartman, P Abdul-Karim, FW Wasman, JK Jesberger, J Lewin, J McCrae, K Ivy, P Remick, SC TI Novel phase I dose de-escalation design trial to determine the biological modulatory dose of the antiangiogenic agent SU5416 SO CLINICAL CANCER RESEARCH LA English DT Article ID GROWTH-FACTOR RECEPTOR; THROMBOTIC THROMBOCYTOPENIC PURPURA; ENDOTHELIAL-CELL APOPTOSIS; MICROVESSEL DENSITY; TUMOR ANGIOGENESIS; CANCER-PATIENTS; INHIBITOR; CARCINOMA; METASTASIS; ACTIVATION AB Purpose: To determine the biological modulatory dose of SU5416, we employed a novel trial design, where "dose de-escalation" was based on demonstrable biological changes observed at the maximum tolerated dose. If such an effect was shown, dose de-escalation to a predefined dose level would occur to determine if the lower dose exhibited the same amount of pharmacodynamic effect as the higher dose. Experimental Design: Ten patients with advanced solid tumors were enrolled at each dose level. One of the following pharmacodynamic effects was considered significant: (a) a 35% decrease in microvessel density in sequential tumor biopsies and (b) a 35% decrease in blood flow within tumor as assessed by dynamic contrast-enhanced magnetic resonance imaging. In addition, soluble E-selectin, soluble intercellular adhesion molecule, soluble vascular cell adhesion molecule, and plasma vascular endothelial growth factor were measured sequentially. Results: Nineteen patients were enrolled. Sequential tumor biopsies in all evaluable patients showed an increase in microvessel density. Only one patient met the intended pharmacodynamic end point of > 35% reduction in blood flow. There was a significant increase in both soluble E-selectin and soluble intercellular adhesion molecule levels pretreatment versus levels at the time of removal of patients from study (P = 0.04 and P = 0.0007, respectively). Levels of serum fibrinogen rose with therapy. There was a trend toward increase in plasma vascular endothelial growth factor levels. Conclusion: SU 5416 does not result in decreased blood flow in tumors or a decrease in microvessel density. This corresponds to the lack of clinical activity seen with this agent. Our clinical trial design termed dose de-escalation is a novel approach to determine the in vivo biological effects of targeted therapies in cancer patients. C1 Case Western Reserve Univ, Div Hematol Oncol, Univ Hosp Cleveland, Cleveland, OH 44106 USA. Case Western Reserve Univ, Div Hematol Oncol, Dept Pathol & Radiol, Cleveland, OH 44106 USA. Case Comprehens Canc Ctr, Dev Therapeut Program, Cleveland, OH USA. NCI, Bethesda, MD 20892 USA. RP Dowlati, A (reprint author), Case Western Reserve Univ, Div Hematol Oncol, Univ Hosp Cleveland, 11100 Euclid Ave, Cleveland, OH 44106 USA. EM afshin.dowlati@CASE.edu OI Radivoyevitch, Tomas/0000-0002-9701-1851 FU NCI NIH HHS [K12 CA76917, P30 CA43703, U01 CA62502]; NCRR NIH HHS [M01-RR-00080] NR 26 TC 26 Z9 27 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 NOV 1 PY 2005 VL 11 IS 21 BP 7938 EP 7944 DI 10.1158/1078-0432.CCR-04-2538 PG 7 WC Oncology SC Oncology GA 984VC UT WOS:000233331400046 PM 16278419 ER PT J AU Vanderver, A Schiffmann, R Timmons, MR Kellersberger, KA Fabris, D Hoffman, EP Maletkovic, J Hathout, Y AF Vanderver, A Schiffmann, R Timmons, MR Kellersberger, KA Fabris, D Hoffman, EP Maletkovic, J Hathout, Y TI Decreased asialotransferrin in cerebrospinal fluid of patients with childhood-onset ataxia and central nervous system hypomyelination/vanishing white matter disease SO CLINICAL CHEMISTRY LA English DT Article ID RESONANCE MASS-SPECTROMETRY; PROTEOMIC ANALYSIS; N-GLYCOSYLATION; TRANSFERRIN; IDENTIFICATION; BRAIN; LEUKOENCEPHALOPATHY; LEUKODYSTROPHIES; TECHNOLOGY; DISORDERS AB Background: A biomarker for the diagnosis of childhood-onset ataxia and central nervous system hypomyelination (CACH)/vanishing white matter disease (VWM) would hive clinical utility and pathophysiologic significance. Methods: We used 2-dimensional gel, electrophoresis/ miss spectrometry to compare the cerebrospinal fluid proteome of patients with mutation-confirmed CACH/ VWM with that of unaffected controls. We characterised selected spots by in-gel digestion, matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry, and nanospray Fourier transform mass spectrometry. Results: A specific transferrin spot pattern was detected in the CSF samples of the CACH/VWM group (n = 7), distinguishing them from the control group (n = 23) and revealing that patients with CACH/VWM have a deficiency of the asialo form of transferrin usually present in healthy cerebrospinal fluid. The glycopeptide structure, determined from isolated transferrin spots by use of in-gel digestion and. extraction, was found to be consistent. with earlier reports. Conclusion: The transferrin isoform abnormality in the cerebrospinal fluid of Patients with CACH/VWM appears unique and is a potential clinical diagnostic biomarker. The rapid, efficient diagnosis of this disorder would hive a significant impact on clinical studies exploring,new strategies for the management and treatment of this disease. (c) 2005 American Association for Clinical Chemistry. C1 Childrens Natl Med Ctr, Childrens Res Inst, Ctr Genet Med, Washington, DC 20010 USA. DMNB, NINDS, NIH, Bethesda, MD USA. Univ Maryland Baltimore Cty, Dept Chem & Biochem, Baltimore, MD USA. RP Hathout, Y (reprint author), Childrens Natl Med Ctr, Childrens Res Inst, Ctr Genet Med, 111 Michigan Ave,NW, Washington, DC 20010 USA. EM yhathout@cnmcresearch.org FU Intramural NIH HHS; NICHD NIH HHS [1P30HD40677-01, HD-P30-40677, K12HD001399]; NIGMS NIH HHS [R01-GM643208] NR 35 TC 33 Z9 33 U1 0 U2 3 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD NOV PY 2005 VL 51 IS 11 BP 2031 EP 2042 DI 10.1373/clinchem.2005.055053 PG 12 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 977HJ UT WOS:000232793700006 PM 16155092 ER PT J AU Kacinko, SL Barnes, AJ Schwilke, EW Cone, EJ Moolchan, ET Huestis, MA AF Kacinko, SL Barnes, AJ Schwilke, EW Cone, EJ Moolchan, ET Huestis, MA TI Disposition of cocaine and its metabolites in human sweat after controlled cocaine administration SO CLINICAL CHEMISTRY LA English DT Article ID GAS-CHROMATOGRAPHY; MASS-SPECTROMETRY; PATCH; ABUSE; SALIVA; DRUGS AB Background: Sweat testing is a noninvasive technique for monitoring drug exposure in treatment, criminal justice, and employment settings. Methods: We evaluated cocaine excretion in 9 participants' sweat after they received 3 low doses (75 mg/70 kg) of cocaine HCl subcutaneously within 1 week and, 3 weeks later, 3 high doses (150 mg/70 kg). Six additional participants completed portions of the study. PharmChek (R) sweat patches (n = 1390) were collected throughout a 3-week washout period, reflecting previously self-administered drugs, and during and after controlled dosing. Results: Cocaine was the primary analyte detected-with 24% of patches positive at the gas chromatography-mass spectrometry limit of quantification of 2.5 ng/patch and 7% of patches at the proposed Substance Abuse and Mental Health Services Administration cutoff of 25 ng/patch. Ecgonine methyl ester (EME) was detected more often and at generally higher concentrations than benzoylecgonine. In patches containing both metabolites, there was no statistically significant difference in the benzoylecgonine/EME ratio based on length of patch wear. During washout, 2 participants' weekly patches tested positive ( >= 25 ng/patch) during the first week; one remained positive during week 2; and none were positive during week 3. Cocaine and EME were detectable within 2 h; benzoylecgonine was not detected until 4-8 h after low doses and slightly. sooner. after high doses. The majority of drug was excreted within 24 h. Over 70% of weekly patches worn during low doses were positive for cocaine ( >= 25 ng/patch), increasing to 100% during high doses. Conclusion: Sweat testing is an effective and reliable method of monitoring cocaine exposure. (c) 2005 American Association for Clinical Chemistry. C1 NIDA, Chem & Drug Metab Intramural Res Program, NIH, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD USA. RP Huestis, MA (reprint author), NIDA, Chem & Drug Metab Intramural Res Program, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM mhuestis@intra.nida.nih.gov FU Intramural NIH HHS NR 16 TC 35 Z9 37 U1 2 U2 6 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD NOV PY 2005 VL 51 IS 11 BP 2085 EP 2094 DI 10.1373/clinchem.2005.054338 PG 10 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 977HJ UT WOS:000232793700012 PM 16166169 ER PT J AU Yang, HY Crawford, N Lukes, L Finney, R Lancaster, M Hunter, KW AF Yang, HY Crawford, N Lukes, L Finney, R Lancaster, M Hunter, KW TI Metastasis predictive signature profiles pre-exist in normal tissues SO CLINICAL & EXPERIMENTAL METASTASIS LA English DT Article DE gene expression; metastasis; microarrays; prognostics; proteomics; susceptibility ID GENE-EXPRESSION PROFILES; COMPLEX TRAIT ANALYSIS; BREAST-CANCER; IMPORTANT DETERMINANT; TUMOR; PROGRESSION; MOUSE; MICE; AMYLASE; CLASSIFICATION AB Previous studies from our laboratory have demonstrated that metastatic propensity is significantly influenced by the genetic background upon which tumors arise. We have also established that human gene expression profiles predictive of metastasis are not only present in mouse tumors with both high and low metastatic capacity, but also correlate with genetic background. These results suggest that human metastasis-predictive gene expression signatures may be significantly driven by genetic background, rather than acquired somatic mutations. To test this hypothesis, gene expression profiling was performed on inbred mouse strains with significantly different metastatic efficiencies. Analysis of previously described human metastasis signature gene expression patterns in normal tissues permitted accurate categorization of high or low metastatic mouse genotypes. Furthermore, prospective identification of animals at high risk of metastasis was achieved by using mass spectrometry to characterize salivary peptide polymorphisms in a genetically heterogeneous population. These results strongly support the role of constitutional genetic variation in modulation of metastatic efficiency and suggest that predictive signature profiles could be developed from normal tissues in humans. The ability to identify those individuals at high risk of disseminated disease at the time of clinical manifestation of a primary cancer could have a significant impact on cancer management. C1 NCI, Lab Populat Genet, CCR, NIH, Bethesda, MD 20892 USA. RP Hunter, KW (reprint author), NCI, Lab Populat Genet, CCR, NIH, Bldg 41 Rm 702,41 Lib Dr, Bethesda, MD 20892 USA. EM hunterk@mail.nih.gov FU Intramural NIH HHS; NCI NIH HHS [Z01 CP010146-06] NR 34 TC 69 Z9 73 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0262-0898 J9 CLIN EXP METASTAS JI Clin. Exp. Metastasis PD NOV PY 2005 VL 22 IS 7 BP 593 EP 603 DI 10.1007/s10585-005-6244-6 PG 11 WC Oncology SC Oncology GA 011XZ UT WOS:000235303800009 PM 16475030 ER PT J AU Ponti, G de Leon, MP Maffei, S Pedroni, M Losi, L Di Gregorio, C Gismondi, V Scarselli, A Benatti, P Roncari, B Seidenari, S Pellacani, G Varotti, C Prete, E Varesco, L Roncucci, L AF Ponti, G de Leon, MP Maffei, S Pedroni, M Losi, L Di Gregorio, C Gismondi, V Scarselli, A Benatti, P Roncari, B Seidenari, S Pellacani, G Varotti, C Prete, E Varesco, L Roncucci, L TI Attenuated familial adenomatous polyposis and Muir-Torre syndrome linked to compound biallelic constitutional MYH gene mutations SO CLINICAL GENETICS LA English DT Article DE APC gene; colon cancer; familial polyposis; microsatellite instability; mismatch repair; Muir-Torre syndrome; MYH gene ID SEBACEOUS GLAND TUMORS; BASE EXCISION-REPAIR; DNA MISMATCH-REPAIR; COLORECTAL-CANCER; MICROSATELLITE INSTABILITY; PHENOTYPE; PROTEIN; COLON; ASSOCIATION; EXPRESSION AB Peculiar dermatologic manifestations are present in several heritable gastrointestinal disorders. Muir-Torre syndrome (MTS) is a genodermatosis whose peculiar feature is the presence of sebaceous gland tumors associated with visceral malignancies. We describe one patient in whom multiple sebaceous gland tumors were associated with early onset colon and thyroid cancers and attenuated polyposis coli. Her family history was positive for colonic adenomas. She had a daughter presenting with yellow papules in the forehead region developed in the late infancy. Skin and visceral neoplasms were tested for microsatellite instability and immunohistochemical status of mismatch repair (MMR), APC and MYH proteins. The proband colon and skin tumors were microsatellite stable and showed normal expression of MMR proteins. Cytoplasmic expression of MYH protein was revealed in colonic cancer cells. Compound heterozygosity due to biallelic mutations in MYH, R168H and 379delC, was identified in the proband. The 11-year-old daughter was carrier of the monoallelic constitutional mutation 379delC in the MYH gene; in the sister, the R168H MYH gene mutation was detected. This report presents an interesting case of association between MYH-associated polyposis and sebaceous gland tumors. These findings suggest that patients with MTS phenotype that include colonic polyposis should be screened for MYH gene mutations. C1 Univ Modena & Reggio Emilia, Dept Internal Med, Modena, Italy. Univ Modena & Reggio Emilia, Dept Pathol, Modena, Italy. Carpi Gen Hosp, Div Pathol, Modena, Italy. Natl Canc Inst, Hereditary Tumors Unit, Genoa, Italy. Univ Modena & Reggio Emilia, Dept Dermatol, Modena, Italy. Univ Bologna, Dept Dermatol, I-40138 Bologna, Italy. S Maria delle Croci Hosp, Dept Pathol, Ravenna, Italy. RP Roncucci, L (reprint author), Univ Modena & Reggio Emilia, Policlin, Dipartimento Med & Special Med, Via Pozzo 71, I-41100 Modena, Italy. EM roncucci@unimo.it RI Ponti, Giovanni/A-5565-2012; Losi, Lorena/B-2583-2012; Ponz de Leon, Maurizio/A-9356-2015; Benatti, Piero/C-1052-2015; Pedroni, Monica/C-9384-2015; Roncucci, Luca/L-1392-2016; pellacani, giovanni/E-8573-2011 OI Ponti, Giovanni/0000-0002-1971-7306; Losi, Lorena/0000-0002-8483-3936; Ponz de Leon, Maurizio/0000-0003-4465-1043; Benatti, Piero/0000-0002-6826-1480; Pedroni, Monica/0000-0001-5374-5362; Roncucci, Luca/0000-0002-0410-1760; pellacani, giovanni/0000-0002-7222-2951 NR 34 TC 50 Z9 51 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0009-9163 J9 CLIN GENET JI Clin. Genet. PD NOV PY 2005 VL 68 IS 5 BP 442 EP 447 DI 10.1111/j.1399-0004.2005.00519.x PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 971NU UT WOS:000232392000010 PM 16207212 ER PT J AU Zaoutis, TE Argon, J Chu, J Berlin, JA Walsh, TJ Feudtner, C AF Zaoutis, TE Argon, J Chu, J Berlin, JA Walsh, TJ Feudtner, C TI The epidemiology and attributable outcomes of candidemia in adults and children hospitalized in the United States: A propensity analysis SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID INTENSIVE-CARE-UNIT; BONE-MARROW TRANSPLANTATION; RISK-FACTORS; FUNGAL-INFECTIONS; FLUCONAZOLE PROPHYLAXIS; NOSOCOMIAL CANDIDEMIA; PEDIATRIC-PATIENTS; CONTROLLED TRIAL; AMPHOTERICIN-B; EXCESS LENGTH AB Background. Candida species are the fourth most common cause of bloodstream infection and are the leading cause of invasive fungal infection among hospitalized patients in the United States. However, the frequency and outcomes attributable to the infection are uncertain. This retrospective study set out to estimate the incidence of candidemia in hospitalized adults and children in the United States and to determine attributable mortality, length of hospital stay, and hospital charges related to candidemia. Methods. We used the Nationwide Inpatient Sample 2000 for adult patients and the Kids' Inpatient Database 2000 for pediatric patients. We matched candidemia-exposed and candidemia-unexposed patients by the propensity scores for the probability of candidemia exposure, which were derived from patient characteristics. Attributable outcomes were calculated as the differences in estimates of outcomes between propensity score-matched patients with and without candidemia. Results. In the United States in 2000, candidemia was diagnosed in an estimated 1118 hospital admissions of pediatric patients and 8949 hospital admissions of adult patients, yielding a frequency of 43 cases per 100,000 pediatric admissions (95% confidence interval [CI], 35-52 cases per 100,000 pediatric admissions) and 30 cases per 100,000 adult admissions (95% CI, 26-34 cases per 100,000 adult admissions). In pediatric patients, candidemia was associated with a 10.0% increase in mortality (95% CI, 6.2%-13.8%), a mean 21.1-day increase in length of stay (95% CI, 14.4-27.8 days), and a mean increase in total per-patient hospital charges of $92,266 (95% CI, $65,058 -$119,474). In adult patients, candidemia was associated with a 14.5% increase in mortality (95% CI, 12.1%-16.9%), a mean 10.1-day increase in length of stay (95% CI, 8.9-11.3 days), and a mean increase in hospital charges of $39,331 (95% CI, $33,604-$45,602). Conclusion. The impact of candidemia on excess mortality, increased length of stay, and the burden of cost of hospitalization underscores the need for improved means of prevention and treatment of candidemia in adults and children. C1 Childrens Hosp Philadelphia, Div Infect Dis, Philadelphia, PA 19104 USA. Childrens Hosp Philadelphia, Div Gen Pediat, Pediat Generalists Res Grp, Philadelphia, PA 19104 USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Biostat, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. NCI, Pediat Oncol Branch, Immunocompromised Host Sect, Bethesda, MD 20892 USA. RP Zaoutis, TE (reprint author), Childrens Hosp Philadelphia, Div Infect Dis, 34th & Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM zaoutis@email.chop.edu FU AHRQ HHS [K08 HS00002, U18-HS10399]; NIAID NIH HHS [1K23 AI0629753-01] NR 36 TC 380 Z9 397 U1 1 U2 9 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 NOV 1 PY 2005 VL 41 IS 9 BP 1232 EP 1239 DI 10.1086/496922 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 971BO UT WOS:000232356300008 PM 16206095 ER PT J AU Lukas, SE Wetherington, CL AF Lukas, SE Wetherington, CL TI Sex- and gender-related differences in the neurobiology of drug abuse SO CLINICAL NEUROSCIENCE RESEARCH LA English DT Article DE drug abuse; sex-related differences; menstrual cycle; subjective mood effects; pharmacokinetics; brain imaging; cocaine ID SELF-ADMINISTERED COCAINE; SMOKED COCAINE; MENSTRUAL-CYCLE; ESTROUS-CYCLE; ORAL-CONTRACEPTIVES; LOCOMOTOR-ACTIVITY; WITHDRAWN PATIENTS; LUTEAL PHASES; FEMALE RATS; HUMANS AB Sex-related responses to drugs of abuse add an important dimension to the larger issue of gender-related differences in epidemiology, prevention strategies and treatment. One of the most important factors in collecting such data is controlling for the many demographic, behavioral, physiological, and hormonal differences that exist between mates and females as these may influence the direct effects of a drug and contribute to a progression from use to abuse to dependence. There are a number of factors that make studying female subjects more challenging. Aside from the obvious hormonal and menstrual cycle differences, there are a variety of gender-related issues that are unique to women and alter the drug abuse profile of certain drugs, regardless of the pharmacological effect. Studies have revealed that the pharmacokinetic profiles (secondary to route of administration) may alter the responses to cocaine and may help explain some of the male/female differences that have been observed, especially via the intranasal route. Sex differences appear to be minimal when cocaine is administered i.v. or by inhalation suggesting that rate of absorption may play an important role in the acute effects of cocaine. In summary, difficulties in conducting studies with females can be overcome with careful planning, time and additional expense. Using controlled laboratory studies, important pharmacokinetic and pharmacodynamic differences in drug effects may modulate male/female expectations about psychoactive drug effects and ultimately play a role in the etiology of drug abuse, dependence and how treatment programs should be structured. Finally, the application of new brain imaging techniques has the potential to reveal the mechanism of these sex-related differences. (c) 2005 Published by Elsevier B.V. on behalf of Association for Research in Nervous and Mental Disease. C1 McLean Hosp, Behav Psychopharmacol Res Lab, Belmont, MA 02478 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NIDA, Bethesda, MD 20892 USA. RP Lukas, SE (reprint author), McLean Hosp, Behav Psychopharmacol Res Lab, 115 Mill St, Belmont, MA 02478 USA. EM lukas@mclean.harvard.edu NR 79 TC 5 Z9 6 U1 3 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1566-2772 J9 CLIN NEUROSCI RES JI Clin. Neurosci. Res. PD NOV PY 2005 VL 5 IS 2-4 BP 75 EP 87 DI 10.1016/j.cnr.2005.08.004 PG 13 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 993CV UT WOS:000233931200004 ER PT J AU Dawson, DA Grant, BF Stinson, FS AF Dawson, DA Grant, BF Stinson, FS TI The AUDIT-C: screening for alcohol use disorders and risk drinking in the presence of other psychiatric disorders SO COMPREHENSIVE PSYCHIATRY LA English DT Article ID NATIONAL EPIDEMIOLOGIC SURVEY; GENERAL-POPULATION SAMPLE; IDENTIFICATION TEST AUDIT; UNITED-STATES; SUBSTANCE-ABUSE; PERSONALITY-DISORDERS; BIPOLAR DISORDER; MAJOR DEPRESSION; DARTMOUTH ASSESSMENT; ANXIETY DISORDERS AB This article examines the performance of the AUDIT-C, as embedded in a large national survey, as a screener for alcohol use disorders (AUDs) and risk drinking among individuals with past-year psychopathology. The analysis is based on data collected in personal interviews from a representative population sample of US adults. The Study population consisted of past-year drinkers with any past-year mood disorder (n = 2818), any past-year anxiety disorder (n = 3173), or any personality disorder (n = 4389). Screening performance was evaluated by means of sensitivity, specificity, and areas under receiver operating characteristic curves (AUCs). The AUCs for the AUDIT-C were from 0.888 to 0.893 for alcohol dependence, front 0.864 to 0.876 for any AUD, and from 0.941 to 0.951 for any AUD or risk drinking-all oil a par with those observed in the general population. Among men, cut points of either >= 5 or >= 6 points (the former favoring sensitivity and the latter favoring specificity) were optimal for detecting dependence, and cut points of >= 5 points were optirrial for any AUD and for any AUD or risk drinking. Among women, a cut point of >= 4 points was optimal for the outcomes of both alcohol dependence and any AUD, whereas a cut point of >= 3 points was preferable for detecting any AUD or risk drinking. Published by Elsevier Inc. C1 NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, Bethesda, MD 20892 USA. RP Dawson, DA (reprint author), NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, Fishers Lane MSC 9304, Bethesda, MD 20892 USA. EM ddawson@mail.nih.gov NR 61 TC 53 Z9 54 U1 5 U2 6 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0010-440X J9 COMPR PSYCHIAT JI Compr. Psychiat. PD NOV-DEC PY 2005 VL 46 IS 6 BP 405 EP 416 DI 10.1016/j.comppsych.2005.01.006 PG 12 WC Psychiatry SC Psychiatry GA 987EI UT WOS:000233500800002 PM 16275207 ER PT J AU Dauter, Z AF Dauter, Z TI Use of polynuclear metal clusters in protein crystallography SO COMPTES RENDUS CHIMIE LA English DT Article DE metal clusters; macromolecular crystallography; phasing; anomalous scattering ID LARGE RIBOSOMAL-SUBUNIT; NUCLEOSOME CORE PARTICLE; IRON-SULFUR PROTEINS; RNA-POLYMERASE-II; X-RAY; CRYSTAL-STRUCTURE; ANGSTROM RESOLUTION; 3-DIMENSIONAL STRUCTURE; ELECTRON-DENSITY; ISOMORPHOUS REPLACEMENT AB Application of polynuclear metal clusters for phasing X-ray crystal structures of macromolecules is discussed. Their strong isomorphous and anomalous scattering signal is particularly useful for phasing structures of large macromolecules and complexes, especially at low resolution. The popularity of the metal clusters in macromolecular crystallography is expected to grow in the future. C1 NCI, MCL, Synchrotron Radiat Res Sect, Argonne Natl Lab,Biosci Div, Argonne, IL 60439 USA. RP Dauter, Z (reprint author), NCI, MCL, Synchrotron Radiat Res Sect, Argonne Natl Lab,Biosci Div, Bldg 202,9700 S Cass Ave, Argonne, IL 60439 USA. EM dauter@anl.gov NR 74 TC 13 Z9 13 U1 1 U2 9 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 1631-0748 J9 CR CHIM JI C. R. Chim. PD NOV-DEC PY 2005 VL 8 IS 11-12 BP 1808 EP 1814 DI 10.1016/j.crci.2005.02.032 PG 7 WC Chemistry, Multidisciplinary SC Chemistry GA 980FB UT WOS:000232998500013 ER PT J AU Um, KS Kwak, YS Cho, H Kim, IK AF Um, KS Kwak, YS Cho, H Kim, IK TI Development of an HL7 interface engine, based on tree structure and streaming algorithm, for large-size messages which include image SO COMPUTER METHODS AND PROGRAMS IN BIOMEDICINE LA English DT Article DE HL7; interface engine; discharge summary; MIME; tree structure; streaming algorithm AB A basic assumption of Health Level Seven (HL7) protocol is 'No limitation of message length'. However, most existing commercial HL7 interface engines do limit message length because they use the string array method, which is run in the main memory for the HL7 message parsing process. Specifically, messages with image and multi-media data create a tong string array and thus cause the computer system to raise critical and fatal problem. Consequently, HL7 messages cannot handle the image and multi-media data necessary in modern medical records. This study aims to solve this problem with the 'streaming algorithm' method. This new method for HL7 message parsing applies the character-stream object which process character by character between the main memory and. hard disk device with the consequence that the processing load on main memory could be alleviated. The main functions of this new engine are generating, parsing, validating, browsing, sending, and receiving HL7 messages. Also, the engine can parse and generate XML-formatted HL7 messages. This new HL7 engine successfully exchanged HL7 messages with 10 megabyte size images and discharge summary information between two university hospitals. Published by Elsevier Ireland Ltd. C1 NCI, Ctr Bioinformat, NIH, Rockville, MD 20852 USA. Kyungpook Natl Univ, Sch Med, Dept Med Informat, Taegu 700422, South Korea. RP Um, KS (reprint author), NCI, Ctr Bioinformat, NIH, 6116 Execut Blvd,Suite 403, Rockville, MD 20852 USA. EM umkis@mail.nih.gov NR 16 TC 6 Z9 8 U1 1 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-2607 J9 COMPUT METH PROG BIO JI Comput. Meth. Programs Biomed. PD NOV PY 2005 VL 80 IS 2 BP 126 EP 140 DI 10.1016/j.cmpb.2005.07.004 PG 15 WC Computer Science, Interdisciplinary Applications; Computer Science, Theory & Methods; Engineering, Biomedical; Medical Informatics SC Computer Science; Engineering; Medical Informatics GA 984ER UT WOS:000233285800004 PM 16181703 ER PT J AU St Claire, MB Kennett, MJ Thomas, ML Daly, JW AF St Claire, MB Kennett, MJ Thomas, ML Daly, JW TI The husbandry and care of dendrobatid frogs SO CONTEMPORARY TOPICS IN LABORATORY ANIMAL SCIENCE LA English DT Article ID POISON FROGS; SKIN ALKALOIDS; POPULATION DECLINES; AMPHIBIAN SKIN; PUMILIO; MYOBATRACHIDAE; AUSTRALIA; BEHAVIOR AB Dendrobatid frogs are studied primarily for the bioactive alkaloids found in their skin. Also known as poison-dart frogs, these animals accumulate toxic alkaloids from dietary sources. The function and uses of the many alkaloids, the alkaloid accumulation system, and the basic biology and physiology of the frogs themselves are of research interest. Here we overview the taxonomy of these frogs and some of the unique aspects of their natural biology and reproduction. We also describe the components of a successful laboratory housing system, including temperature, lighting, humidity, ventilation, nutrition, health considerations, and handling. A brief summary of dendrobatid research highlights is provided. C1 NIDDK, Lab Anim Sci Sci, DHHS, NIH, Bethesda, MD 20892 USA. NIDDK, Bioorgan Chem Lab, DHHS, NIH, Bethesda, MD USA. Penn State Univ, Anim Resource Program, University Pk, PA 16802 USA. NIH, Div Vet Resources, ORS, DHHS, Bethesda, MD 20892 USA. RP St Claire, MB (reprint author), NIDDK, Lab Anim Sci Sci, DHHS, NIH, Bethesda, MD 20892 USA. NR 45 TC 2 Z9 2 U1 4 U2 10 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 NOV PY 2005 VL 44 IS 6 BP 8 EP 14 PG 7 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 987FD UT WOS:000233502900001 PM 16370573 ER PT J AU Gozalo, AS Schwiebert, RS Metzner, W Lawson, GW AF Gozalo, AS Schwiebert, RS Metzner, W Lawson, GW TI Spontaneous, generalized lipidosis in captive greater horseshoe bats (Rhinolophus ferrumequinum) SO CONTEMPORARY TOPICS IN LABORATORY ANIMAL SCIENCE LA English DT Article ID CARDIAC LIPIDOSIS; HEARTS; INNERVATION; FLIGHT; CELLS; DIETS; ACID AB During a routine 6-month quarantine period, 3 of 34 greater horseshoe bats (Rhinolophus ferrumequinum) captured in mainland China and transported to the United States for use in echolocation studies were found dead with no prior history of illness. All animals were in good body condition at the time of death. At necropsy, a large amount of white fat was found within the subcutis, especially in the sacrolumbar region. The liver, kidneys, and heart were diffusely tan in color. Microscopic examination revealed that hepatocytes throughout the liver were filled with lipid, and in some areas, lipid granulomas were present. Renal lesions included moderate amounts of lipid in the cortical tubular epithelium and large amounts of protein and lipid within Bowman's capsules in the glomeruli. In addition, one bat had large lipid vacuoles diffusely distributed throughout the myocardium. The exact pathologic mechanism inducing the hepatic, renal, and cardiac lipidosis is unknown. The horseshoe bats were captured during hibernation and immediately transported to the United States. It is possible that the large amount of fat stored coupled with changes in photoperiod, lack of exercise, and/or the stress of captivity might have contributed to altering the normal metabolic processes, leading to anorexia and consequently lipidosis in these animals. C1 Univ Calif Los Angeles, David Geffen Sch Med, Div Lab Anim Med, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Physiol Sci, Los Angeles, CA USA. RP Gozalo, AS (reprint author), NIAID, Comparat Med Branch, 9000 Rockville Pike, Bethesda, MD 20892 USA. FU NIDCD NIH HHS [R01 DC5400] NR 27 TC 3 Z9 3 U1 0 U2 3 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 NOV PY 2005 VL 44 IS 6 BP 49 EP 52 PG 4 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 987FD UT WOS:000233502900009 PM 16370581 ER PT J AU Khil, PR Camerini-Otero, RD AF Khil, PR Camerini-Otero, RD TI Molecular features and functional constraints in the evolution of the mammalian X chromosome SO CRITICAL REVIEWS IN BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Review DE retrotransposition; sex determination; meiotic sex chomosome inactivation; MSCI; epigenetics; sexual antagonism; sex-biased genes ID LYON REPEAT HYPOTHESIS; EARLY MOUSE EMBRYOS; HUMAN Y-CHROMOSOME; SEX-CHROMOSOMES; GENE-EXPRESSION; LINKED GENES; CAENORHABDITIS-ELEGANS; DOSAGE COMPENSATION; COGNITIVE FUNCTION; BIASED EXPRESSION AB Recent advances in genomic sequencing of multiple organisms have fostered significant advances in our understanding of the evolution of the sex chromosomes. The integration of this newly available sequence information with functional data has facilitated a considerable refinement of our conceptual framework of the forces driving this evolution. Here we address multiple functional constraints that were encountered in the evolution of the X chromosome and the impact that this evolutionary history has had on its modern behavior. C1 NIDDK, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA. RP Camerini-Otero, RD (reprint author), NIDDK, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA. EM camerini@ncifcrf.gov OI Khil, Pavel/0000-0002-4903-8777 NR 128 TC 7 Z9 7 U1 1 U2 4 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1040-9238 J9 CRIT REV BIOCHEM MOL JI Crit. Rev. Biochem. Mol. Biol. PD NOV-DEC PY 2005 VL 40 IS 6 BP 313 EP 330 DI 10.1080/10409230500356703 PG 18 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 001DF UT WOS:000234513100001 PM 16338684 ER PT J AU Hartz, AMS Bauer, B Baehr, CH Miller, DS Fricker, G AF Hartz, AMS Bauer, B Baehr, CH Miller, DS Fricker, G TI Drug delivery across the blood-brain barrier SO CURRENT NANOSCIENCE LA English DT Article DE blood-brain barrier; p-glycoprotein; drug delivery systems; nanoparticles; immuno-liposomes ID PREGNANE-X-RECEPTOR; VECTOR-MEDIATED STRATEGY; P-GLYCOPROTEIN EXPRESSION; RENAL PROXIMAL TUBULE; ENDOTHELIAL-CELLS; IN-VITRO; MULTIDRUG-RESISTANCE; TRANSFERRIN RECEPTOR; ENHANCED DELIVERY; NUCLEAR RECEPTORS AB The blood brain barrier, formed by brain capillary endothelial cells, represents the major obstacle for drug entry into the central nervous system. Efforts are ongoing to overcome this barrier without causing permanent damage to brain tissue. The present review attempts to provide key information on cerebral microvessel anatomy, features contributing to barrier function and current approaches in overcoming the blood-brain barrier using cellular and molecular methodologies to transfer drugs to the brain as well as intelligent drug delivery systems. C1 Univ Heidelberg, Inst Pharm & Mol Biotechnol, D-69120 Heidelberg, Germany. NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. RP Fricker, G (reprint author), Univ Heidelberg, Inst Pharm & Mol Biotechnol, D-69120 Heidelberg, Germany. EM gert.fricker@uni-hd.de NR 90 TC 1 Z9 1 U1 5 U2 7 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1573-4137 J9 CURR NANOSCI JI Curr. Nanosci. PD NOV PY 2005 VL 1 IS 3 BP 203 EP 209 DI 10.2174/157341305774642948 PG 7 WC Biotechnology & Applied Microbiology; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary SC Biotechnology & Applied Microbiology; Science & Technology - Other Topics; Materials Science GA 992PA UT WOS:000233894900003 ER PT J AU Jia, L AF Jia, L TI Nanoparticle formulation increases oral bioavailability of poorly soluble drugs: Approaches, experimental evidences and theory SO CURRENT NANOSCIENCE LA English DT Article DE nanoparticle formulation; nanonization; bioavailability ID CARBON NANOTUBES; RAT; DNA; MICROSPHERES; NANOSPHERES; DELIVERY; CARRIER; MUCOSA AB The increasing frequency at which poorly soluble new chemical entities are being discovered raises concerns in the pharmaceutical industry about drugability associated with erratic dissolution and low bioavailability of these hydrophobic compounds. Nanonization provides a plausible pharmaceutical basis for enhancing oral bioavailability and therapeutic effectiveness of these compounds by increasing their surface area. This paper surveys methods available to pharmaceutical manufacturing nanoparticles, including wet chemical processes, media milling, high pressure homogenization, gas-phase synthesis, and form-in-place processes, and elaborates physicochemical rational and gastrointestinal physiological basis upon which nano-drugs can be readily absorbed. Relevant examples are illustrated to show that nano-drugs permeate Caco-2 cell monolayer fast and are well absorbed into animal systemic circulation with high T-max and AUC, resulting in oral bioavailability higher than their counterpart micro-drugs. The size-dependent permeability and bioavailability should be given particular consideration in the development of potent end selective drug candidates with poor aqueous solubility. C1 NCI, EPN, NIH, Dev Therapeut Program, Rockville, MD 20852 USA. RP Jia, L (reprint author), NCI, EPN, NIH, Dev Therapeut Program, Rm 8042,6130 Execut Blvd, Rockville, MD 20852 USA. EM jiale@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 38 TC 30 Z9 30 U1 0 U2 13 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1573-4137 J9 CURR NANOSCI JI Curr. Nanosci. PD NOV PY 2005 VL 1 IS 3 BP 237 EP 243 DI 10.2174/157341305774642939 PG 7 WC Biotechnology & Applied Microbiology; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary SC Biotechnology & Applied Microbiology; Science & Technology - Other Topics; Materials Science GA 992PA UT WOS:000233894900006 PM 19865587 ER PT J AU Jia, L AF Jia, L TI Global governmental investment in nanotechnologies SO CURRENT NANOSCIENCE LA English DT Article DE nanotechnology; governmental nanotechnology funding ID SCIENCE; JAPAN AB Nanotechnologies seem to have huge potential to bring benefits in areas as diverse as drug development, water decontamination, information and communication infrastructures, and the production of stronger, lighter and perfect nanomaterials. This potential attracts global investment from governments and private sectors in nanotechnologies with the hopes that R&D and commercial applications of nanomaterials, nanodevices, nanoparticles and nanodrugs will provide new impetus, after the ebb-tides of biotechnology and dotcom, to turn faltering economies around. The global governmental funding has been actively promoting industrial and academic cooperation to realize big prosperity from the nanotechnologies. This article summarizes historic trends and status of global governmental supports for nanotechnologies. C1 NCI, EPN, NIH, Dev Therapeut Program, Rockville, MD 20852 USA. RP Jia, L (reprint author), NCI, EPN, NIH, Dev Therapeut Program, Rm 8042,6130 Execut Blvd, Rockville, MD 20852 USA. EM jiale@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 12 TC 8 Z9 8 U1 3 U2 12 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1573-4137 J9 CURR NANOSCI JI Curr. Nanosci. PD NOV PY 2005 VL 1 IS 3 BP 263 EP 266 DI 10.2174/157341305774642957 PG 4 WC Biotechnology & Applied Microbiology; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary SC Biotechnology & Applied Microbiology; Science & Technology - Other Topics; Materials Science GA 992PA UT WOS:000233894900009 PM 19865495 ER PT J AU Du, QZ Ito, Y AF Du, QZ Ito, Y TI Review on scale-up of coil column countercurrent chromatographs SO CURRENT PHARMACEUTICAL ANALYSIS LA English DT Review DE coil column countercurrent chromatography; high-speed countercurrent chromatography; cross axis countercurrent chromatography; slow rotary countercurrent chromatography; scale-up; review ID PLANET CENTRIFUGE; PARTITION EFFICIENCY; SEPARATION; EXTRACT; PHASE; PURIFICATION AB Coil column countercurrent chromatography (CC-CCC) has been intensively used for the separation of natural products. Most of these separations have been successfully performed on a laboratory scale. However, scaling-up of this technique for industrial separations is still a challenge. In the present paper scale-up of coil column countercurrent chromatographs with three types of column rotation including high-speed planetary motion around its horizontal axis, cross-axis medium-speed planetary motion and slow rotation around its horizontal axis are reviewed. Up to now, the column capacities of high-speed countercurrent chromatographs, cross-axis countercurrent chromatographs and slow rotary countercurrent chromatographs reach 4.6, 2.5 and 40 liters, respectively. An evaluation scaling-up each type of CC-CCC is made. C1 Zhejiang Gongshang Univ, Inst Food & Biol Engn, Hangzhou 310035, Peoples R China. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Du, QZ (reprint author), Zhejiang Gongshang Univ, Inst Food & Biol Engn, 149 Jiaogong Rd, Hangzhou 310035, Peoples R China. EM qizhendu@mail.hzic.edu.cn NR 34 TC 2 Z9 2 U1 1 U2 5 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1573-4129 J9 CURR PHARM ANAL JI Curr. Pharm. Anal. PD NOV PY 2005 VL 1 IS 3 BP 309 EP 318 DI 10.2174/157341205774597887 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 056MG UT WOS:000238526600008 ER PT J AU Telford, W Murga, M Hawley, T Hawley, R Packard, B Komoriya, A Haas, F Hubert, C AF Telford, W Murga, M Hawley, T Hawley, R Packard, B Komoriya, A Haas, F Hubert, C TI DPSS yellow-green 561-nm lasers for improved fluorochrome detection by flow cytometry SO CYTOMETRY PART A LA English DT Article DE solid state laser; yellow-green laser; phycoerythrin; DsRed ID CELLS AB Introduction: Blue-green 488-nm laser sources are widespread in flow cytometry but suffer some drawbacks for cell analysis, including their excitation of endogenous proteins (resulting in high cellular autofluorescence) and their less-than-optimal coincidence with the excitation maxima of commonly used fluorochromes, including the phycoerythrins (PE). Longer wavelength lasers such as green helium-neons and, more recently, diode-pumped solid state (DPSS) 532-nm sources have previously been employed to overcome these difficulties and improve overall sensitivity for PE. In this study, we evaluate an even longer wavelength DPSS 561-nm for its ability to improve PE and DsRed fluorescent protein detection sensitivity. Methods: A DPSS 561-nm laser emitting at 10 mW was mounted onto a BD LSR II. Mouse thymoma cells labeled with cell surface marker antibodies conjugated to the Rand B-forms of PE were analyzed and compared with conventional 488-nm excitation using the same bandpass filters and signal travel distances. A similar analysis was carried out with cell lines expressing the red fluorescent protein DsRed, several green-yellow excited low molecular weight fluorochromes, and a rhodamine-based caspase substrate. Additionally, cells labeled with PE and co-labeled with fluorescein or simultaneously expressing green fluorescent protein (GFP) were analyzed to determine if PE excitation at 561 nm with simultaneous fluorescein/GFP detection was feasible. Results: The DPSS 561-nm laser gave a several-fold improvement in the fluorochrome to autofluorescence ratios between PE-labeled cells and unlabeled controls. Analysis of cells expressing the fluorescent protein DsRed with the DPSS 561-nm source gave a 6-7-fold improvement in sensitivity over 488-nm excitation, and gave excellent excitation of yellow-green excited fluorochromes and rhodamine-based physiological probes. Yellow-green laser light also caused virtually no impingement on the spatially separated fluorescein/GFP detector, a significant problem with green laser sources, and also allowed simultaneous analysis of GFP and PE with virtually no signal overlap or requirement for color compensation. Conclusions: DPSS 561-nm laser excitation gave significantly improved sensitivity for both PE-labeled and DsRed expressing cells, with little contamination of a typical fluorescein/GFP detector. Published 2005 Wiley-Liss, Inc.(dagger). C1 NCI, Expt Transplantat & Immunol Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. George Washington Univ, Med Ctr, Flow Cytometry Core Facil, Washington, DC 20037 USA. George Washington Univ, Med Ctr, Dept Anat & Cell Biol, Washington, DC 20037 USA. Oncoimmunin Inc, Gaithersburg, MD USA. Melles Griot Laser Grp Inc, Carlsbad, CA USA. RP Telford, W (reprint author), NCI, Expt Transplantat & Immunol Branch, Canc Res Ctr, NIH, Bldg 10 Room 12C121,9000 Rockville Pike, Bethesda, MD 20892 USA. EM teffordw@mail.nih.gov NR 17 TC 49 Z9 55 U1 0 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4922 J9 CYTOM PART A JI Cytom. Part A PD NOV PY 2005 VL 68A IS 1 BP 36 EP 44 DI 10.1002/cyto.20182 PG 9 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 980OH UT WOS:000233027300006 PM 16163703 ER PT J AU Louzao, R Wong, J Denny, T AF Louzao, R Wong, J Denny, T TI Comparison of fingerstick versus venipuncture collection of blood for CD4+T-cell testing SO CYTOMETRY PART B-CLINICAL CYTOMETRY LA English DT Meeting Abstract CT 20th Annual Meeting of the Clinical-Cytometry-Society CY OCT 16-18, 2005 CL Savannah, GA SP Clin Cytometry Soc C1 Univ Med & Dent New Jersey, NIAID, DAIDS, Immunol Qual Assessment Program, Newark, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4949 J9 CYTOM PART B-CLIN CY JI Cytom. Part B-Clin. Cytom. PD NOV PY 2005 VL 68B IS 1 MA 27 BP 63 EP 63 PG 1 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 980CU UT WOS:000232992300034 ER PT J AU Thangaraju, M Rudelius, M Bierie, B Raffeld, M Sharan, S Hennighausen, L Huang, AM Sterneck, E AF Thangaraju, M Rudelius, M Bierie, B Raffeld, M Sharan, S Hennighausen, L Huang, AM Sterneck, E TI C/EBP delta is a crucial regulator of pro-apoptotic gene expression during mammary gland involution SO DEVELOPMENT LA English DT Article DE mammary gland; involution; C/EBP; apoptosis; mouse ID BINDING-PROTEIN-DELTA; WILD-TYPE P53; ACUTE-PHASE RESPONSE; GROWTH-FACTOR-BETA; EPITHELIAL-CELLS; ADIPOCYTE DIFFERENTIATION; SIGNALING PATHWAY; MICE LACKING; STAT3; ACTIVATION AB The STAT3 transcription factor is an important initiator of mammary gland involution in the mouse. This work shows that the STAT3 target gene CCAAT/enhancer binding protein delta (C/EBP delta) is a crucial mediator of proapoptotic gene expression events in mammary epithelial cells. In the absence of C/EBP delta, involution is delayed, the pro-apoptotic genes encoding p53, BAK, IGFBP5 and SGP2/clusterin are not activated, while the anti-apoptotic genes coding for BFL1 and Cyclin D1 are not repressed. Consequently, p53 targets such as survivin, BRCA1, BRCA2 and BAX are not regulated appropriately and protease activation is delayed. Furthermore, expression of MMP3 and C/EBP beta during the second phase of involution is perturbed in the absence of C/EBP delta. In HC11 cells, C/EBP delta alone is sufficient to induce IGFBP5 and SGP2. It also suppresses Cyclin 131 expression and cooperates with p53 to elicit apoptosis. This study places C/EBP delta between STAT3 and several pro- and anti-apoptotic genes promoting the physiological cell death response in epithelial cells at the onset of mammary gland involution. C1 Natl Canc Inst, Lab Prot Dynam & Signaling, Canc Res Ctr, Ft Detrick, MD 21702 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NIDDKD, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA. RP Sterneck, E (reprint author), Med Coll Georgia, Dept Biochem & Mol Biol, Augusta, GA 30912 USA. EM sterneck@ncifcrf.gov FU Intramural NIH HHS NR 75 TC 62 Z9 64 U1 0 U2 9 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 NOV PY 2005 VL 132 IS 21 BP 4675 EP 4685 DI 10.1242/dev.02050 PG 11 WC Developmental Biology SC Developmental Biology GA 987VB UT WOS:000233544400004 PM 16192306 ER PT J AU Li, CL Xu, XL Nelson, DK Williams, T Kuehn, MR Deng, CX AF Li, CL Xu, XL Nelson, DK Williams, T Kuehn, MR Deng, CX TI FGFR1 function at the earliest stages of mouse limb development plays an indispensable role in subsequent autopod morphogenesis SO DEVELOPMENT LA English DT Article DE apoptosis; BMP4; MKP3; DKK1; ALX4 ID GROWTH-FACTOR RECEPTORS; APICAL ECTODERMAL RIDGE; VERTEBRATE LIMB; SONIC-HEDGEHOG; CONDITIONAL INACTIVATION; FEEDBACK LOOP; HOX GENES; MICE; BUD; CHICK AB Fibroblast growth factors (FGFs) and their receptors have been implicated in limb development. However, because of early post-implantation lethality associated with fibroblast growth factor receptor 1 (FGFR1) deficiency, the role of this receptor in limb development remains elusive. To overcome embryonic lethality, we have performed a conditional knockout of Fgfr1 using the Cre-LoxP approach. We show that Cre-mediated deletion of Fgfr1 in limb mesenchyme, beginning at a time point slightly after the first sign of initial budding, primarily affects formation of the first one or two digits. In contrast, deletion of Fgfr1 at an earlier stage, prior to thickening of limb mesenchyme, results in more severe defects, characterized by malformation of the AER, diminished Shh expression and the absence of the majority of the autopod skeletal elements. We show that FGFR1 deficiency does not affect cell proliferation. Instead, it triggers cell death and leads to alterations in expression of a number of genes involved in apoptosis and digit patterning, including increased expression of Bmp4, Dkk1 and Alx4, and downregulation of MKP3. These data demonstrate that FGF/FGFR1 signals play indispensable roles in the early stages of limb initiation, eliciting a profound effect on the later stages of limb development, including cell survival, autopod formation and digit patterning. C1 NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. Univ Colorado, Hlth Sci Ctr, Dept Craniofacial Biol & Cellular & Dev Biol, Denver, CO 80262 USA. Natl Canc Inst, Lab Prot Dynam & Signaling, Canc Res Ctr, Ft Detrick, MD 21702 USA. RP Deng, CX (reprint author), NIDDK, Genet Dev & Dis Branch, NIH, 10-9N105,10 Ctr Dr, Bethesda, MD 20892 USA. EM chuxiad@bdg10.niddk.nih.gov RI Kuehn, Michael/A-4573-2014; deng, chuxia/N-6713-2016 OI Kuehn, Michael/0000-0002-7703-9160; FU Intramural NIH HHS; NIDCR NIH HHS [R01 DE12728] NR 59 TC 41 Z9 41 U1 0 U2 0 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 NOV PY 2005 VL 132 IS 21 BP 4755 EP 4764 DI 10.1242/dev.02065 PG 10 WC Developmental Biology SC Developmental Biology GA 987VB UT WOS:000233544400011 PM 16207751 ER PT J AU Insel, TR AF Insel, TR TI Developmental psychobiology for public health: A bridge for translational research SO DEVELOPMENTAL PSYCHOBIOLOGY LA English DT Review ID MENTAL-ILLNESS; MOUSE GENOME; SCHIZOPHRENIA; PSYCHIATRY; CHILDHOOD; BEHAVIOR; TARGETS; MICE C1 NIMH, Bethesda, MD 20892 USA. RP Insel, TR (reprint author), NIMH, Bethesda, MD 20892 USA. EM insel@mail.nih.gov NR 30 TC 10 Z9 10 U1 0 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0012-1630 J9 DEV PSYCHOBIOL JI Dev. Psychobiol. PD NOV PY 2005 VL 47 IS 3 BP 209 EP 216 DI 10.1002/dev.20089 PG 8 WC Developmental Biology; Psychology SC Developmental Biology; Psychology GA 982BL UT WOS:000233131700003 PM 16252289 ER PT J CA Natl-Inst-Child-Hlth-Human-Dev-Ear TI Oral language and reading: Reply to Bracken (2005) SO DEVELOPMENTAL PSYCHOLOGY LA English DT Article DE emergent literacy; language; literacy AB Early language competence in preschool relates both directly and indirectly to elementary school, reading in both 1st and 3rd grades. Further, comprehensive language skills are more strongly related to early reading than are vocabulary scores alone. In response to a challenge by S. A. Bracken (2005), the current article reaffirms the National Institute of Child Health and Human Development Early Child Care Research Network's (2005) findings. C1 NICHD, Rockville, MD 20852 USA. NR 9 TC 0 Z9 0 U1 0 U2 1 PU AMER PSYCHOLOGICAL ASSOC/EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0012-1649 J9 DEV PSYCHOL JI Dev. Psychol. PD NOV PY 2005 VL 41 IS 6 BP 1000 EP 1002 DI 10.1037/0012-1649.41.6.1000 PG 3 WC Psychology, Developmental SC Psychology GA 990AN UT WOS:000233715700016 ER PT J AU Shearer, J Fueger, PT Bracy, DP Wasserman, DH Rottman, JN AF Shearer, J Fueger, PT Bracy, DP Wasserman, DH Rottman, JN TI Partial gene deletion of heart-type fatty acid-binding protein limits the severity of dietary-induced insulin resistance SO DIABETES LA English DT Article ID MUSCLE GLUCOSE-UPTAKE; HUMAN SKELETAL-MUSCLE; MICE; EXERCISE; RATS; METABOLISM; TISSUES AB The aim of this study was to determine the contribution of heart-type fatty acid-binding protein (H-FABP) to glucose and long-chain fatty acid (LCFA) utilization in dietary-induced insulin resistance. We tested the hypothesis that H-FABP facilitates increases in LCFA flux present in glucose-intolerant states and that a partial reduction in the amount of this protein would compensate for all or part of the impairment. Transgenic H-FABP heterozygotes (HET) and wild-type (WT) littermates were studied following chow diet (CHD) or high-fat diet (HFD) for 12 weeks. Catheters were surgically implanted in the carotid artery and jugular vein for sampling and infusions, respectively. Following 5 days of recovery, mice received either a saline infusion or underwent a euglycemic insulin clamp (4 mU (.) kg(-1 .) min(-1)) for 120 min. At 90 min, a bolus of 2-deoxyglucose and [I-125]-15-(rho-iodophenyl)-3-R,S-methylpentadecanoic acid were administered to obtain indexes of glucose and LCFA utilization. At 120 min, skeletal muscles were excised for tracer determination. All HFD mice were obese and hyperinsulinemic; however, only HFD-WT mice were hyperglycemic. Glucose infusion rates during insulin clamps were 49 +/- 4, 59 +/- 4, 16 +/- 4, and 33 +/- 4 mg (.) kg(-1) (.) min(-1) for CHD-WT, CHD-HET, HFD-WT, and HFD-HET mice, respectively, showing that HET limited the severity of whole-body insulin resistance with HFD. Insulin-stimulated muscle glucose utilization was attenuated in HFD-WT but unaffected in HFD-HET mice. Conversely, rates of LCFA clearance were increased with HFD feeding in RFD-WT but not in HFD-HET mice. In conclusion, a partial reduction in H-FABP protein normalizes fasting glucose levels and improves whole-body insulin sensitivity in HFD-fed mice despite obesity. C1 Vanderbilt Univ, Sch Med, Dept Physiol & Mol Biophys, Nashville, TN 37212 USA. Vanderbilt Univ, Sch Med, Mouse Metab Phenotyping Ctr, Nashville, TN 37212 USA. Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37212 USA. RP Shearer, J (reprint author), Univ Calgary, Fac Med, Ctr Mouse Genom, Rm 2502,3330 Hosp Dr,NW, Calgary, AB T2N 4N1, Canada. EM jshearer@ucalgary.ca RI Fueger, Patrick/G-8956-2013 FU NIDDK NIH HHS [U24-DK-59636, DK-54902] NR 31 TC 22 Z9 23 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 NOV PY 2005 VL 54 IS 11 BP 3133 EP 3139 DI 10.2337/diabetes.54.11.3133 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 980MR UT WOS:000233023100010 PM 16249436 ER PT J AU Rutter, MK Meigs, JB Sullivan, LM D'Agostino, RB Wilson, PW AF Rutter, MK Meigs, JB Sullivan, LM D'Agostino, RB Wilson, PW TI Insulin resistance, the metabolic syndrome, and incident cardiovascular events in the Framingham Offspring Study SO DIABETES LA English DT Article ID HOMEOSTASIS MODEL ASSESSMENT; TREATMENT PANEL-III; CORONARY-HEART-DISEASE; GLUCOSE-TOLERANCE; PLASMA-GLUCOSE; SENSITIVITY; RISK; PREDICTOR; ATHEROSCLEROSIS; CHOLESTEROL AB The metabolic syndrome and insulin resistance have been related to incident cardiovascular disease (CVD), but it is uncertain if metabolic syndrome predicts CVD independent of insulin resistance. Our study sample included 2,898 people without diabetes or CVD at baseline. Metabolic syndrome was defined by the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) criteria. Insulin resistance was defined by the homeostasis model assessment (HOMAIR) and by Gutt et al.'s insulin sensitivity index (ISI0,120). Age- and sex-adjusted proportional hazards regression models assessed the association of baseline metabolic syndrome and insulin resistance to 7-year CVD risk (186 events). Metabolic syndrome and both measures of insulin resistance were individually related to incident CVD (age-and sex-adjusted hazard ratio [HR] for metabolic syndrome [present versus absent]: 2.0 [95% CI 1.5-2.6], P = 0.0001; for HOMA-IR: 1.9 [1.2-2.9], P = 0.003; and for ISI0,120 [both highest versus lowest quartilel: 0.5 [0.3-0.7], P = 0.001). In models adjusted for age, sex, LDL cholesterol, and smoking status and including metabolic syndrome, ISI0,120 levels were independently related to incident CVD (0.5 [0.3-0.8], P = 0.004), whereas HOMA-IR levels were not (1.3 [0.8-2.1], P = 0.24); metabolic syndrome was associated with increased CVD risk in both models (HR 1.6, P <= 0.007 in both). In conclusion, metabolic syndrome and ISI0,120 but not HOMA-IR independently predicted incident CVD. Metabolic syndrome may not capture all the CVD risk associated with insulin resistance. C1 Chester Hosp NHS Trust, Dept Med, Chester CH2 1UL, Cheshire, England. Univ Manchester, Dept Med, Manchester M13 9PL, Lancs, England. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Gen Internal Med Unit, Boston, MA 02114 USA. Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. Med Univ S Carolina, Charleston, SC 29425 USA. Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA. RP Rutter, MK (reprint author), Chester Hosp NHS Trust, Dept Med, Liverpool Rd, Chester CH2 1UL, Cheshire, England. EM martin.rutter@coch.nhs.uk OI Rutter, Martin/0000-0001-6380-539X FU NHLBI NIH HHS [N01-HC-25195, R01-HL 073272] NR 34 TC 164 Z9 173 U1 1 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD NOV PY 2005 VL 54 IS 11 BP 3252 EP 3257 DI 10.2337/diabetes.54.11.3252 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 980MR UT WOS:000233023100026 PM 16249452 ER PT J AU Beisswenger, PJ Drummond, KS Nelson, RG Howell, SK Szwergold, BS Mauer, M AF Beisswenger, PJ Drummond, KS Nelson, RG Howell, SK Szwergold, BS Mauer, M TI Susceptibility to diabetic nephropathy is related to dicarbonyl and oxidative stress SO DIABETES LA English DT Article ID EARLY NATURAL-HISTORY; STRUCTURAL-FUNCTIONAL RELATIONSHIPS; GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE; IN-VIVO; GLOMERULAR STRUCTURE; GLYOXALASE SYSTEM; KIDNEY-FUNCTION; CROSS-LINKING; COMPLICATIONS; METHYLGLYOXAL AB Dicarbonyl and oxidative stress may play important roles in the development of diabetes complications, and their response to hyperglycemia could determine individual susceptibility to diabetic nephropathy. This study examines the relationship of methylglyoxal, 3-deoxyglucosone (3DG), and oxidative stress levels to diabetic nephropathy risk in three populations with diabetes. All subjects in the Overt Nephropathy Progressor/Nonprogressor (ONPN) cohort (n = 14), the Natural History of Diabetic Nephropathy study (NHS) cohort (n = 110), and the Pima Indian cohort (n = 45) were evaluated for clinical nephropathy, while renal structural measures of fractional mesangial volume [Vv(Mes/glom)] and glomerular basement membrane (GBM) width were determined by electron microscopy morphometry in the NHS and Pima Indian cohorts. Methylglyoxal and 3DG levels reflected dicarbonyl stress, while reduced glutathione (GSH) and urine 8-isoprostane (8-IP) measured oxidative stress. Cross-sectional measures of methylglyoxal production by red blood cells incubated in 30 mmol/l glucose were increased in nephropathy progressors relative to nonprogressors in the ONPN (P = 0.027) and also reflected 5-year GBM thickening in the NHS cohort (P = 0.04). As nephropathy progressed in the NHS cohort, in vivo levels of methylglyoxal (P = 0.036), 3DG (P = 0.004), and oxidative stress (8-IP, P = 0.007 and GSH, P = 0.005) were seen, while increased methylglyoxal levels occurred as nephropathy progressed (P = 0.0016) in the type 2 Pima Indian cohort. Decreased glyceraldehyde-3-phosphate dehydrogenase activity also correlated with increased methylglyoxal levels (P = 0.003) in the NHS cohort. In conclusion, progression of diabetic nephropathy is significantly related to elevated dicarbonyl stress and possibly related to oxidative stress in three separate populations, suggesting that these factors play a role in determining individual susceptibility. C1 Dartmouth Coll Sch Med, Dept Med Diabet Endocrinol & Metab, Lebanon, NH 03756 USA. Dartmouth Hitchcock Med Ctr, Dept Med Diabet Endocrinol & Metab, Lebanon, NH 03756 USA. Dartmouth Coll Sch Med, Dept Med, Hanover, NH 03756 USA. Dartmouth Hitchcock Med Ctr, Hanover, NH 03756 USA. McGill Univ, Dept Pediat, Montreal, PQ H3A 2T5, Canada. NIDDK, Phoenix Epidemiol & Clin Res Branch, Phoenix, AZ USA. Univ Minnesota, Dept Pediat, Minneapolis, MN 55455 USA. RP Beisswenger, PJ (reprint author), Dartmouth Coll Sch Med, Dept Med Diabet Endocrinol & Metab, 1 Med Ctr Dr, Lebanon, NH 03756 USA. EM paul.j.beisswenger@dartmouth.edu RI Nelson, Robert/B-1470-2012 FU NIDDK NIH HHS [DK-002933, DK-62901, R01-DK-62995] NR 55 TC 106 Z9 117 U1 1 U2 4 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 NOV PY 2005 VL 54 IS 11 BP 3274 EP 3281 DI 10.2337/diabetes.54.11.3274 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 980MR UT WOS:000233023100029 PM 16249455 ER PT J AU Sorkin, JD Muller, DC Fleg, JL Andres, R AF Sorkin, JD Muller, DC Fleg, JL Andres, R TI The relation of fasting and 2-h postchallenge plasma glucose concentrations to mortality - Data from the Baltimore Longitudinal Study of Aging with a critical review of the literature SO DIABETES CARE LA English DT Review ID CARDIOVASCULAR-DISEASE MORTALITY; DIABETES-MELLITUS; RISK-FACTOR; DIAGNOSTIC-CRITERIA; ALL-CAUSE; HYPERGLYCEMIA; PREDICTOR; WOMEN; MEN AB OBJECTIVE - Under the auspices of the National Institutes of Health, American Diabetes Association, and World Health Organization, expert committees lowered the fasting plasma glucose (FPG) concentration diagnostic for diabetes from 7.8 to 7.0 mmol/l and defined 6.1 - 6.9 mmol/l as impaired fasting glucose (IFG) and < 6.1 mmol/l as normal fasting glucose. In 2003, IFG was lowered to 5.6 - 6.9 mmol/l and normal fasting glucose to < 5.6 mmol/l. Reports of the relationship between glucose concentration and all-cause mortality have been inconsistent. It is not known if the 2-h plasma glucose (2hPG) concentration from an oral glucose tolerance test (OGTT) adds to the predictive power of FPG. RESEARCH DESIGN AND METHODS - We followed 1,236 men for an average of 13.4 years to determine the relationship between both FPG and 2hPG and all-cause mortality. RESULTS - Risk for mortality did not increase until the FPG exceeded 6.1 mmol/l. Risk increased by similar to 40% in the 6.1 - 6.9 mmol/l range and doubled when FPG ranged from 7.0 to 7.7 mmol/l. A combination of the 2hPG and FPG allowed better estimation of risk than the FPG alone. Within any category of FPG, risk generally increased as the 2hPG increased, and within any category of 2hPG, risk generally increased as the FPG increased. CONCLUSIONS - These data support the decision to lower the FPG diagnostic for diabetes from 7.8 to 7.0 mmol/l, show that both IFG and impaired glucose tolerance have risks between the normal and diabetic ranges, and show that the OGTT adds predictive power to that of FPG alone and should not be abandoned. The lowering of IFG to 5.6 mmol/l from 6.1 mmol/l, at least for mortality, is, however, not supported by our results. C1 NIA, Intramural Res Program, Ctr Gerontol Res, Baltimore, MD 21224 USA. Univ Maryland, Sch Med, Baltimore Vet Affairs Hosp Geriat, Baltimore, MD 21201 USA. NHLBI, Clin Trials Sci Res Grp, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. RP Sorkin, JD (reprint author), Univ Maryland, Sch Med, Baltimore VA Med Ctr, Div Gerontol, 10 N Greene St,GRECC,BT-18-GR, Baltimore, MD 21201 USA. EM jsorkin@grecc.umaryland.edu FU Intramural NIH HHS; NIA NIH HHS [K01AG001054] NR 26 TC 104 Z9 109 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 NOV PY 2005 VL 28 IS 11 BP 2626 EP 2632 DI 10.2337/diacare.28.11.2626 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 001PH UT WOS:000234548300004 PM 16249530 ER PT J AU Carnethon, MR Bertoni, AG Shea, S Greenland, P Ni, HY Jacobs, DR Saad, M Liu, K AF Carnethon, MR Bertoni, AG Shea, S Greenland, P Ni, HY Jacobs, DR Saad, M Liu, K TI Racial/ethnic differences in subclinical atherosclerosis among adults with diabetes - The multiethnic study of atherosclerosis SO DIABETES CARE LA English DT Article ID PERIPHERAL ARTERIAL-DISEASE; COMPUTED-TOMOGRAPHY; WHITE SUBJECTS; UNITED-STATES; RISK-FACTORS; PREVALENCE; POPULATION; INDEX; CALCIFICATION; CALCIUM C1 Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. Wake Forest Univ, Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27109 USA. Columbia Univ, Mailman Sch Publ, Dept Epidemiol, New York, NY USA. Columbia Univ, Med Ctr, Dept Gen Med, New York, NY USA. NHLBI, NIH, Bethesda, MD 20892 USA. Univ Minnesota, Sch Publ Hlth, Div Epidemiol, Minneapolis, MN USA. Univ Oslo, Dept Nutr, Oslo, Norway. Univ Calif Los Angeles, Div Endocrinol, Los Angeles, CA USA. RP Carnethon, MR (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, 680 N Lake Shore Dr,Suite 1102, Chicago, IL 60611 USA. EM carnethon@northwestern.edu FU NHLBI NIH HHS [N01-HC-95169, 1K01 HL73249-01, N01-HC-95159, N01-HC-95166] NR 15 TC 36 Z9 37 U1 0 U2 2 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 NOV PY 2005 VL 28 IS 11 BP 2768 EP 2770 DI 10.2337/diacare.28.11.2768 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 001PH UT WOS:000234548300028 PM 16249554 ER PT J AU Kovacs, P Ma, L Hanson, RL Franks, P Stumvoll, M Bogardus, C Baier, LJ AF Kovacs, P Ma, L Hanson, RL Franks, P Stumvoll, M Bogardus, C Baier, LJ TI Genetic variation in UCP2 (uncoupling protein-2) is associated with energy metabolism in Pima Indians SO DIABETOLOGIA LA English DT Article DE energy metabolism; genetics; obesity; type 2 diabetes mellitus; uncoupling protein-2 ID MIDDLE-AGED HUMANS; INSULIN-SECRETION; COMMON POLYMORPHISM; OBESITY; PROMOTER; RISK AB Aims/hypothesis: Uncoupling protein-2 (UCP2) is thought to play a role in insulin secretion and the development of obesity. In this study, we investigated the effects of genetic variation in UCP2 on type 2 diabetes and obesity, as well as on metabolic phenotypes related to these diseases, in Pima Indians. Methods: The coding and untranslated regions of UCP2, and approximately 1 kb of the 5' upstream region, were sequenced in DNA samples taken from 83 extremely obese Pima Indians who were not first-degree relatives. Results: Five variants were identified: (1) a -866G/A in the 5' upstream region; (2) a G/A in exon 2; (3) a C/T resulting in an Ala55Val substitution in exon 4; and (4, 5) two insertion/deletions (ins/del; 45-bp and 3-bp) in the 3' untranslated region. Among the 83 subjects whose DNA was sequenced, the -866G/A was in complete genotypic concordance with the Ala55Val and the 3-bp ins/del polymorphism. The G/A polymorphism in exon 2 was extremely rare. To capture the common variation in this gene for association analyses, the -866G/A variant (as a representative of Ala55Val and the 3-bp ins/del polymorphism) and the 45-bp ins/del were also genotyped for 864 full-blooded Pima Indians. Neither of these variants was associated with type 2 diabetes or body mass index. However, in a subgroup of 185 subjects who had undergone detailed metabolic measurements, these variants were associated with 24-h energy expenditure as measured in a human metabolic chamber (p=0.007 for the 45-bp ins/del and p=0.03 for the -866G/A after adjusting for age, sex, family membership, fat-free mass and fat mass). Conclusions/interpretation: Our data indicate that variation in UCP2 may play a role in energy metabolism, but this gene does not contribute significantly to the aetiology of type 2 diabetes and/or obesity in Pima Indians. C1 Univ Leipzig, Dept Med 3, D-04103 Leipzig, Germany. NIDDK, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ USA. RP Kovacs, P (reprint author), Univ Leipzig, Dept Med 3, Philipp Rosenthal Str 27, D-04103 Leipzig, Germany. EM Peter.Kovacs@medizin.uni-leipzig.de RI Hanson, Robert/O-3238-2015 OI Hanson, Robert/0000-0002-4252-7068 NR 10 TC 31 Z9 33 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD NOV PY 2005 VL 48 IS 11 BP 2292 EP 2295 DI 10.1007/s00125-005-1934-9 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 983QW UT WOS:000233248200016 PM 16167150 ER PT J AU Kohn, EC Travers, LA Kassis, J Broome, U Klominek, J AF Kohn, EC Travers, LA Kassis, J Broome, U Klominek, J TI Malignant effusions are sources of fibronectin and other promigratory and proinvasive components SO DIAGNOSTIC CYTOPATHOLOGY LA English DT Article; Proceedings Paper CT 31st European Congress of Cytology CY OCT 02-05, 2005 CL Paris, FRANCE DE metastasis; ovarian cancer; proteolysis; motility ID AUTOCRINE MOTILITY FACTOR; OVARIAN-CARCINOMA CELLS; MATRIX METALLOPROTEINASES; LYSOPHOSPHATIDIC ACID; SEROUS EFFUSIONS; IV COLLAGENASE; EXTRACELLULAR-MATRIX; NONMALIGNANT ASCITES; MESOTHELIAL CELLS; GROWTH-FACTORS AB Metastatic dissemination is the primary cause of death in ovarian cancer (OvCa) patients, and dissemination to pleural and peritoneal effusions is a common clinical event. Effusion samples were collected from 15 OvCa patients. Twenty-six samples were collected prospectively, two were archival, and eight were taken from patients with other malignancies. Tweny-nine samples were from malignant ascites, and seven specimens were pleural fluids. In addition, six ascites and two pleural fluids from? noncancer patients were studied as effusion controls. Effusion supernatants were tested for migration-stimulation activity, using A2058 human melanoma cells as the index responder cell. Malignant samples induced a 400-1200% increase in migration. Sixty percent of the migration was inhibited by incubation of the maligant fluid with antifibronectin (FN) antibody. in contrast to 75% inhibition of control fluid-stimulated migration (P = 0.017). Gelatin zymography and Western blot analyses showed that latent and activated MMP-2 and MMP-9 collagenases, and tissue inhibitor of metalloproteinase-2 (TIMP-2) were present ill all malignant fluids. Serial samples vvere taken from several patients, and a trend for correlation between MMPs and clinical behavior of the tumors was shown. Free TIMP-2 correlated with CA-125 levels in two patients for whom serial samples were available. The demonstration of promigratory and proinvasive activity in malignant effusions is consistent with their association with other metastatic disease in OvCa patients and their, function as a haven for metastatic cells. C1 NCI, Canc Res Ctr, Pathol Lab, Mol Signaling Sect, Bethesda, MD 20892 USA. Huddinge Hosp, Karolinska Inst, S-14186 Huddinge, Sweden. RP Kohn, EC (reprint author), NCI, Canc Res Ctr, Pathol Lab, Mol Signaling Sect, 10 Ctr Dr MSC 1500, Bethesda, MD 20892 USA. EM eklb@nih.gov NR 40 TC 16 Z9 16 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 8755-1039 J9 DIAGN CYTOPATHOL JI Diagn. Cytopathol. PD NOV PY 2005 VL 33 IS 5 BP 300 EP 308 DI 10.1002/dc.20279 PG 9 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 981DV UT WOS:000233068500004 PM 16240400 ER PT J AU Kassis, J Klominek, J Kohn, EC AF Kassis, J Klominek, J Kohn, EC TI Tumor microenvironment: What can effusions teach us? SO DIAGNOSTIC CYTOPATHOLOGY LA English DT Article; Proceedings Paper CT 31st European Congress of Cytology CY OCT 02-05, 2005 CL Paris, FRANCE DE mesothelial cells; LPA; ovarian cancer; VEGF ID ENDOTHELIAL GROWTH-FACTOR; LYSOPHOSPHATIDIC ACID LPA; MATRIX METALLOPROTEINASES; OVARIAN-CARCINOMA; MALIGNANT EFFUSIONS; PLEURAL EFFUSIONS; SEROUS EFFUSIONS; EXTRACELLULAR-MATRIX; MESOTHELIAL CELLS; NECROSIS-FACTOR AB Malignant effusions, which are composed of malignant pleural and peritoneal fluid, are an unusual manifestation of cancer and frequently portend a poor prognosis. Neoplastic cells that disseminate into cavities containing effusions are highly metastatic and possess a strong autonomous proliferative drive while concurrently being stimulatory of exudative effusions. Most effusions will respond to transient therapeutic intervention, including the obliteration of potential space via pleurodesis. Cure, however, is rare, thus making effusions a biologically, biochemically, and clinically important topic of study. The local microenvironment that supports malignant growth, invasion, and dissemination of the solid primary tumor into the vasculature is composed of activated stroma that includes scaffolding consisting of materials that promote the tumor function, and vascular structures to provide conduits for travel and nutrient delivery. Less is understood about the tumor-cell microenvironment in malignant effusions. The fluid nature of such a microenvironment when compared with the solid primary tumor may have significant implications for disease dissemination and progression. Dissecting the signaling activity and components of such microenvironments will improve our understanding and ultimately our ability to provide better patient care. C1 NCI, Ctr Canc Res, Pathol Lab, Mol Signaling Sect, Bethesda, MD 20892 USA. Huddinge Hosp, Karolinska Inst, S-14186 Huddinge, Sweden. RP Kohn, EC (reprint author), NCI, Ctr Canc Res, Pathol Lab, Mol Signaling Sect, 10 Ctr Dr,MSC 1500, Bethesda, MD 20892 USA. EM eklb@nih.gov NR 35 TC 31 Z9 31 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 8755-1039 J9 DIAGN CYTOPATHOL JI Diagn. Cytopathol. PD NOV PY 2005 VL 33 IS 5 BP 316 EP 319 DI 10.1002/dc.20280 PG 4 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 981DV UT WOS:000233068500006 PM 16240401 ER PT J AU Chou, SP Grant, BF Dawson, DA Stinson, FS Saha, T Pickering, RP AF Chou, SP Grant, BF Dawson, DA Stinson, FS Saha, T Pickering, RP TI Twelve-month prevalence and changes in driving after drinking: United States, 1991-1992 and 2001-2002 SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE alcohol-impaired driving; drinking and driving; sociodemographic characteristics; high risk subgroups; changes in drinking and driving ID HEAVY DRINKING; ALCOHOL-USE; RISK; PATTERNS; AGE; POPULATION; STUDENTS; DRIVERS AB Background: Drinking and driving has been identified as one of the most important contributors of motor vehicle fatalities. This paper addressed the existing gap in our public health knowledge regarding the Current prevalence of driving after drinking and how this has changed over the past decade. Methods: Prevalence rates of drinking and driving in 2001-2002, and changes in those prevalence rates between 1991-1992 and 2001-2002 were examined in two large nationally representative surveys of the U.S. population. Results: overall, the prevalence of driving after drinking was 2.9% in 2001-2002 representing approximately six million U.S. adults. This rate was about three quarters of the rate observed in 1991-1992 (3.7%), reflecting a 22% reduction. Generally, the male-female differentials in the rate of driving after drinking decreased over the past decade. However, the sex ratios increased substantially for underaged youth over the past decade, reflecting the sharp decrease in prevalence of driving after drinking among 18-20-year-old women. Constant and emerging subgroups at high risk for drinking and driving included Whites, Native Americans, males, underaged young adults and 21-25-year-olds. Conclusions: The results of this study highlighted the need to continue to monitor prevalence and changes in driving after drinking. Results are discussed in the context of strengthening existing prevention and intervention efforts and developing new programs with the sociodemographic differentials observed in this Study in mind. Published by Elsevier Ireland Ltd. C1 NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, Dept Hlth & Human Serv,NIH, Bethesda, MD 20892 USA. RP Chou, SP (reprint author), NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, Dept Hlth & Human Serv,NIH, Room 3073,MS 9304,5635 Fishers Lane, Bethesda, MD 20892 USA. EM pchou@mail.nih.gov NR 31 TC 25 Z9 25 U1 0 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD NOV 1 PY 2005 VL 80 IS 2 BP 223 EP 230 DI 10.1016/j.drugalcdep.2005.03.013 PG 8 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 980MO UT WOS:000233022800008 PM 16216703 ER PT J AU Kim, C Cho, YC Kang, CH Kim, MG Lee, HS Cho, EG Park, D AF Kim, C Cho, YC Kang, CH Kim, MG Lee, HS Cho, EG Park, D TI Filamin is essential for shedding of the transmembrane serine protease, epithin SO EMBO REPORTS LA English DT Article DE ectodomain shedding; epithin; filamin; actin filaments; PMA ID ACTIVATION; LOCALIZATION; MATRIPTASE; INHIBITORS; CANCER; ALPHA; CELLS AB Epithin is a type II transmembrane serine protease that exists in a soluble and membrane-bound form. Shedding is thought to be important in regulating its action, but little is known regarding the intracellular events that trigger such shedding. Here, we show that phorbol myristate acetate (PMA) causes the release of epithin. It also causes accumulation of the protein at the site of cell - cell contacts, and this accumulation is dependent on the formation of cortical actin. In addition, we have identified the actin-binding protein, filamin, as the linker between epithin and the actin cytoskeleton. The interaction of epithin and filamin was enhanced by PMA, and epithin was not released from filamin-deficient M2 cells. We also show that the release of epithin does not require its own activity and is blocked by a metalloprotease inhibitor, GM6001. These results show that filamin has an essential role in shedding by linking epithin to the as yet unidentified metalloprotease-shedding enzyme(s). C1 Seoul Natl Univ, Sch Biol Sci, Seoul 151742, South Korea. NIAID, Thym Mol Dev Unit, Cellular & Mol Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Park, D (reprint author), Seoul Natl Univ, Sch Biol Sci, Seoul 151742, South Korea. EM depark@snu.ac.kr NR 16 TC 24 Z9 24 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1469-221X J9 EMBO REP JI EMBO Rep. PD NOV PY 2005 VL 6 IS 11 BP 1045 EP 1051 DI 10.1038/sj.embor.7400534 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 979TE UT WOS:000232966900013 PM 16170303 ER PT J AU Aviles, JM Aviles, RJ AF Aviles, JM Aviles, RJ TI Advances in cardiac biomarkers SO EMERGENCY MEDICINE CLINICS OF NORTH AMERICA LA English DT Article ID ACUTE CORONARY SYNDROMES; ACUTE MYOCARDIAL-INFARCTION; BRAIN NATRIURETIC PEPTIDE; ISCHEMIA-MODIFIED ALBUMIN; CONGESTIVE-HEART-FAILURE; PUBLIC-HEALTH PRACTICE; ST-SEGMENT ELEVATION; SOLUBLE CD40 LIGAND; TROPONIN-I LEVELS; ACUTE CHEST-PAIN AB The diagnostic and prognostic roles of new and established cardiac biomarkers are continually changing. This update article discusses clinical diagnosis as a framework for directing biomarker testing. Markers are reviewed in the settings of acute coronary syndromes, decompensated heart failure, and noncardiac clinical scenarios. C1 Boston Univ, Sch Med, Quincy Med Ctr, Dept Emergency Med, Quincy, MA 02169 USA. NHLBI, Cardiovasc Branch, Div Intramural Res, NIH, Bethesda, MD 20892 USA. RP Aviles, JM (reprint author), Boston Univ, Sch Med, Quincy Med Ctr, Dept Emergency Med, Quincy, MA 02169 USA. EM javil001@umaryland.edu NR 67 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0733-8627 J9 EMERG MED CLIN N AM JI Emerg. Med. Clin. N. Am. PD NOV PY 2005 VL 23 IS 4 BP 959 EP + DI 10.1016/j.emc.2005.07.016 PG 18 WC Emergency Medicine SC Emergency Medicine GA 979ZM UT WOS:000232983700003 PM 16199333 ER PT J AU Arnold, JT Blackman, MR AF Arnold, JT Blackman, MR TI Does DHEA exert direct effects on androgen and estrogen receptors, and does it promote or prevent prostate cancer? SO ENDOCRINOLOGY LA English DT Editorial Material ID DEHYDROEPIANDROSTERONE-SULFATE; ADRENAL ANDROGENS; GENE-EXPRESSION; IN-VIVO; BETA; CELLS; PROLIFERATION; CARCINOMA; MEN; DIHYDROTESTOSTERONE C1 NIH, Natl Ctr Complementary & Alternat Med, Endocrine Sect, Clin Invest Lab, Bethesda, MD 20892 USA. RP Arnold, JT (reprint author), NIH, Natl Ctr Complementary & Alternat Med, Endocrine Sect, Clin Invest Lab, Bethesda, MD 20892 USA. NR 37 TC 20 Z9 20 U1 1 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD NOV PY 2005 VL 146 IS 11 BP 4565 EP 4567 DI 10.1210/en.2005-0901 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 974IP UT WOS:000232585200001 PM 16227445 ER PT J AU Ward, MH deKok, TM Levallois, P Brender, J Gulis, G Nolan, BT VanDerslice, J AF Ward, MH deKok, TM Levallois, P Brender, J Gulis, G Nolan, BT VanDerslice, J TI Workgroup report: Drinking-water nitrate and health-recent findings and research needs SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE adverse reproductive outcomes; methemoglobinemia; neoplasms; nitrate; nitrite; N-nitroso compounds; water pollution ID N-NITROSO COMPOUNDS; NEURAL-TUBE DEFECTS; CHILDHOOD DIABETES-MELLITUS; INFLAMMATORY-BOWEL-DISEASE; NON-HODGKINS-LYMPHOMA; NITRIC-OXIDE; CANCER-RISK; RED MEAT; ENDOGENOUS FORMATION; ULCERATIVE-COLITIS AB Human alteration of the nitrogen cycle has resulted in steadily accumulating nitrate in our water resources. The U.S. maximum contaminant level and World Health Organization guidelines for nitrate in drinking water were promulgated to protect infants from developing methemoglobinemia, an acute condition. Some scientists have recently suggested that the regulatory limit for nitrate is overly conservative; however, they have not thoroughly considered chronic health outcomes. In August 2004, a symposium on drinking-water nitrate and health was held at the International Society for Environmental Epidemiology meeting to evaluate nitrate exposures and associated health effects in relation to the current regulatory limit. The contribution of drinking-water nitrate toward endogenous formation of N-nitroso compounds was evaluated with a focus toward identifying subpopulations with increased rates of nitrosation. Adverse health effects may be the result of a complex interaction of the amount of nitrate ingested, the concomitant ingestion of nitrosation cofactors and precursors, and specific medical conditions that increase nitrosation. Workshop participants concluded that more experimental studies are needed and that a particularly fruitful approach may be to conduct epidemiologic studies among susceptible subgroups with increased endogenous nitrosation. The few epidemiologic studies that have evaluated intake of nitrosation precursors and/or nitrosation inhibitors have observed elevated risks for colon cancer and neural tube defects associated with drinking-water nitrate concentrations below the regulatory limit. The role of drinking-water nitrate exposure as a risk factor for specific cancers, reproductive outcomes, and other chronic health effects must be studied more thoroughly before changes to the regulatory level for nitrate in drinking water can be considered. C1 NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv,NIH, Bethesda, MD 20892 USA. Univ Maastricht, Dept Hlth Risk Anal & Toxicol, Maastricht, Netherlands. Ctr Hosp Univ Quebec, Inst Natl Sante Publ Quebec, Quebec City, PQ, Canada. Ctr Hosp Univ Quebec, Unite Rech Sante Publ, Quebec City, PQ, Canada. Texas state Univ, Dept Hlth Serv Res, San Marcos, TX USA. Univ Trnava, Dept Publ Hlth, Trnava, Slovakia. Univ So Denmark, Dept Hlth Promot Res, Odense, Denmark. US Geol Survey, Reston, VA 22092 USA. Washington State Dept Hlth, Olympia, WA USA. RP Ward, MH (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv,NIH, 6120 Execut Blvd,EPS 8104, Bethesda, MD 20892 USA. EM wardm@mail.nih.gov RI Gulis, Gabriel/E-4505-2013; de Kok, Theo/G-6213-2014 NR 99 TC 260 Z9 273 U1 14 U2 96 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 EI 1552-9924 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD NOV PY 2005 VL 113 IS 11 BP 1607 EP 1614 DI 10.1289/ehp.8043 PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 979BI UT WOS:000232916700046 PM 16263519 ER PT J AU Reinlib, L AF Reinlib, L TI Meeting report: Structural determination of environmentally responsive proteins SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE Environmental Genome Project; gene-environment interactions; protein structure; structural biology ID DATABASE; DESIGN; GENOME; SNP AB The three-dimensional structure of gene products continues to be a missing lynchpin between linear genome sequences and our understanding of the normal and abnormal function of proteins and pathways. Enhanced activity in this area is likely to lead to better understanding of how discrete changes in molecular patterns and conformation underlie functional changes in protein complexes and, with it, sensitivity of an individual to an exposure. The National Institute of Environmental Health Sciences convened a workshop of experts in structural determination and environmental health to solicit advice for future research in structural resolution relative to environmentally responsive proteins and pathways. The highest priorities recommended by the workshop were to support studies of structure, analysis, control, and design of conformational and functional states at molecular resolution for environmentally responsive molecules and complexes; promote understanding of dynamics, kinetics, and ligand responses; investigate the mechanisms and steps in posttranslational modifications, protein partnering, impact of genetic polymorphisms on structure/function, and ligand interactions; and encourage integrated experimental and computational approaches. The workshop participants also saw value in improving the throughput and purity of protein samples and macromolecular assemblies; developing optimal processes for design, production, and assembly of macromolecular complexes; encouraging studies on protein-protein and macromolecular interactions; and examining assemblies of individual proteins and their functions in pathways of interest for environmental health. C1 Natl Inst Environm Hlth Sci, Susceptibil & Populat Hlth Branch, Div Extramural Res & Training, US Dept HHS,NIH, Res Triangle Pk, NC 27709 USA. RP Reinlib, L (reprint author), Natl Inst Environm Hlth Sci, Susceptibil & Populat Hlth Branch, Div Extramural Res & Training, US Dept HHS,NIH, Room 3453,79 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM reinlib@niehs.nih.gov NR 20 TC 0 Z9 0 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 NOV PY 2005 VL 113 IS 11 BP 1622 EP 1626 DI 10.1289/ehp.8129 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 979BI UT WOS:000232916700048 PM 16263521 ER PT J AU Schwartz, DA AF Schwartz, DA TI The NIEHS responds to hurricane katrina SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material C1 NIEHS, Res Triangle Pk, NC 27709 USA. RP Schwartz, DA (reprint author), NIEHS, Res Triangle Pk, NC 27709 USA. EM david.schwartz@niehs.nih.gov NR 0 TC 4 Z9 4 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 NOV PY 2005 VL 113 IS 11 BP A722 EP A722 PG 1 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 979BI UT WOS:000232916700002 PM 16263489 ER PT J AU Chen, AM Zhang, J Zhou, LF Gao, ES Chen, L Rogan, WJ Wolff, MS AF Chen, AM Zhang, J Zhou, LF Gao, ES Chen, L Rogan, WJ Wolff, MS TI DDT serum concentration and menstruation among young Chinese women SO ENVIRONMENTAL RESEARCH LA English DT Article DE DDT; DDE; menstruation; endocrine disruptor; reproduction ID BREAST-CANCER RISK; POLYCHLORINATED-BIPHENYLS; CYCLE LENGTH; BLOOD-LEVELS; MILK; LACTATION; EXPOSURE; ORGANOCHLORINES; HYDROCARBONS; PESTICIDES AB High DDE and DDT concentrations were found to be associated with shortened menstrual cycle length in Laotian immigrants to the United States. We examined this issue in a sample of young Chinese women. A total of 60 women aged 20-24 years were enrolled in three maternal and child health clinics (20 from urban, 20 from suburban, 20 from rural) in Shanghai, China, and vicinity, in 1998. Of these women, 47 who did not use hormonal contraceptives and had valid menstrual cycle characteristics were included in the analysis for associations among serum DDE and DDT concentration and menstrual cycle length, duration of menses, and heaviness of menstrual flow. In univariate analysis, higher p,p'-DDE concentration was associated with longer menstrual cycle length (0.66 day per 10pg/L, 95% confidence interval [CI]: 0.21, 1.11 day). With adjustment for age, body mass index, education, occupation, and resident location, the estimate was 0.42 day (95% CI: -0.35, 1.19 day). p,p'-DDE was not associated with duration of menses or heaviness of menstrual flow. Neither p,p'-DDT nor o,p'-DDT were associated with menstrual cycle length, duration of menses or heaviness of menstrual flow. The study largely suggests no association between DDE and DDT concentrations and menstrual cycle characteristics in young Chinese women, though the weak-to-no correlation of DDE with menstrual cycle length merits further study. Published by Elsevier Inc. C1 NICHHD, Epidemiol Branch, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. Natl Inst Environm Hlth Sci, Epidemiol Branch, Dept Hlth & Human Serv, NIH, Res Triangle Pk, NC USA. Shanghai Inst Planned Parenthood Res, Dept Reprod Epidemiol & Social Sci, Shanghai, Peoples R China. Mt Sinai Sch Med, Dept Community & Prevent Med, New York, NY USA. RP Zhang, J (reprint author), NICHHD, Epidemiol Branch, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. EM zhangj@mail.nih.gov RI Rogan, Walter/I-6034-2012 OI Rogan, Walter/0000-0002-9302-0160 NR 31 TC 15 Z9 15 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 0013-9351 J9 ENVIRON RES JI Environ. Res. PD NOV PY 2005 VL 99 IS 3 BP 397 EP 402 DI 10.1016/j.envres.2004.12.015 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 993MA UT WOS:000233957000013 PM 16307982 ER PT J AU Desai, MY Lai, SH Barmet, C Weiss, RG Stuber, M AF Desai, MY Lai, SH Barmet, C Weiss, RG Stuber, M TI Reproducibility of 3D free-breathing magnetic resonance coronary vessel wall imaging SO EUROPEAN HEART JOURNAL LA English DT Article DE coronary artery vessel wall imaging; magnetic resonance imaging; reproducibility ID RANDOMIZED CONTROLLED-TRIAL; MR-ANGIOGRAPHY; ATHEROSCLEROSIS; RESOLUTION; HEART AB Aims Although the coronary artery vessel wall can be imaged non-invasively using magnetic resonance imaging (MRI), the in vivo reproducibility of wall thickness measures has not been previously investigated. Using a refined magnetization preparation scheme, we sought to assess the reproducibility of three-dimensional (3D) free-breathing black-blood coronary MRI in vivo. Methods and results MRI vessel wall scans parallel to the right coronary artery (RCA) were obtained in 18 healthy individuals (age range 25-43, six women), with no known history of coronary artery disease, using a 3D dual-inversion navigator-gated black-blood spiral imaging sequence. Vessel wall scans were repeated 1 month later in eight subjects. The visible vessel wall segment and the wall thickness were quantitatively assessed using a semi-automatic tool and the intra-observer, inter-observer, and inter-scan reproducibilities were determined. The average imaged length of the RCA vessel wall was 44.5 +/- 7 mm. The average wall thickness was 1.6 +/- 0.2 mm. There was a highly significant intra-observer (r=0.97), inter-observer (r=0.94), and inter-scan (r=0.90) correlation for wall thickness (all P < 0.001). There was also a significant agreement for intra-observer, inter-observer, and inter-scan measurements on Bland-Altman analysis. The intra-class correlation coefficients for intra-observer (r=0.97), inter-observer (r=0.92), and inter-scan (r=0.86) analyses were also excellent. Conclusion The use of black-blood free-breathing 3D MRI in conjunction with semi-automated analysis software allows for reproducible measurements of right coronary arterial vessel-wall thickness. This technique may be well-suited for non-invasive longitudinal studies of coronary atherosclerosis. C1 Johns Hopkins Univ, Sch Med, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD 21287 USA. Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21287 USA. Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21287 USA. Johns Hopkins Univ, Sch Med, Dept Elect Engn, Baltimore, MD 21287 USA. NIH, Bethesda, MD 20892 USA. Univ Zurich, Inst Biomed Engn, Zurich, Switzerland. ETH, Zurich, Switzerland. RP Stuber, M (reprint author), Johns Hopkins Univ, Sch Med, Russell H Morgan Dept Radiol & Radiol Sci, JHOC 4243,601,N Caroline St, Baltimore, MD 21287 USA. EM mstuber@mri.jhu.edu RI Stuber, Matthias/B-2949-2010 OI Stuber, Matthias/0000-0001-9843-2028 FU NHLBI NIH HHS [HL61912] NR 27 TC 27 Z9 30 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD NOV PY 2005 VL 26 IS 21 BP 2320 EP 2324 DI 10.1093/eurheartj/ehi357 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 976QI UT WOS:000232747900020 PM 15972291 ER PT J AU Hodge, DR Hurt, EM Farrar, WL AF Hodge, DR Hurt, EM Farrar, WL TI The role of IL-6 and STAT3 in inflammation and cancer SO EUROPEAN JOURNAL OF CANCER LA English DT Review DE inflammation; STATs; IL-6; cancer; JAK; kinase inhibitor; resistance to chemotherapy ID AUTOCRINE GROWTH-FACTOR; MULTIPLE-MYELOMA CELLS; MARROW STROMAL CELLS; NF-KAPPA-B; BALB/C MICE; DNA-BINDING; IN-VITRO; ACTIVATING MUTATIONS; SIGNALING PATHWAYS; NEGATIVE REGULATOR AB The defense of the host from foreign pathogens is the commonly accepted function of the vertebrate immune system. A complex system consisting of many differing cells and structures communicating by both soluble and cell bound ligands, serves to protect the host from infection, and plays a role in preventing the development of certain types of tumours. Numerous signalling pathways are involved in the coordination of the immune system, serving both to activate and attenuate its responses to attack. The ability of the immune system, specifically those cells involved in acute inflammatory responses, to mediate the directed (and sometimes indirect) killing of cells and pathogens, make it a potential threat to host survival. Furthermore, the production and release of various survival factors such as the pleiotropic cytokine IL-6, a major mediator of inflammation and activator of signal transducer and activator of transcription 3, serves to block apoptosis in cells during the inflammatory process, keeping them alive in very toxic environments. Unfortunately, these same pathways serve also to maintain cells progressing towards neoplastic growth, protecting them from cellular apoptotic deletion and chemotherapeutic drugs. Here, we discuss the relationships between cancer and inflammation, and some of the molecular mechanisms involved in mediating the unintended consequences of host defense and tumour survival. (c) 2005 Elsevier Ltd. All rights reserved. C1 NCI, Canc Res Ctr, Cytokine Mol Mechanisms Sect, Lab Mol Immunoregulat, Frederick, MD 21702 USA. NCI, SAIC Frederick, Basic Res Program, Frederick, MD 21702 USA. RP Farrar, WL (reprint author), NCI, Canc Res Ctr, Cytokine Mol Mechanisms Sect, Lab Mol Immunoregulat, POB B,Bldg 560,Rm 31-76, Frederick, MD 21702 USA. EM farrar@mail.ncifcrf.gov NR 103 TC 417 Z9 454 U1 14 U2 66 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD NOV PY 2005 VL 41 IS 16 BP 2502 EP 2512 DI 10.1016/j.ejca.2005.08.016 PG 11 WC Oncology SC Oncology GA 987MT UT WOS:000233522700011 PM 16199153 ER PT J AU Terpos, E Rezvani, K Basu, S Milne, AE Rose, PE Scott, GL Rahemtulla, A Samson, D Apperley, JF AF Terpos, E Rezvani, K Basu, S Milne, AE Rose, PE Scott, GL Rahemtulla, A Samson, D Apperley, JF TI Plasmacytoma relapses in the absence of systemic progression post-high-dose therapy for multiple myeloma SO EUROPEAN JOURNAL OF HAEMATOLOGY LA English DT Article DE plasmacytoma; multiple myeloma; transplantation; relapse ID BONE-MARROW-TRANSPLANTATION; STEM-CELL TRANSPLANTATION; GRAFT-VERSUS-MYELOMA; MYELOABLATIVE ALLOGENEIC TRANSPLANTATION; CENTRAL-NERVOUS-SYSTEM; EXTRAMEDULLARY RELAPSE; SINGLE-CENTER; THALIDOMIDE; REMISSION; ANGIOGENESIS AB Autologous (ASCT) and allogeneic stem cell transplantations (alloBMT) are well-established therapies for multiple myeloma. However, patients continue to relapse at a constant rate. We present here 15 out of 163 patients who underwent SCT and relapsed with plasmacytomas only without evidence of bone marrow disease progression (14/147 post-ASCT and 1/16 post-alloBMT). The median time from SCT to plasmacytoma relapse was 24 months. The sites of plasmacytoma included bone, skin, rectum, and testicles. Five patients were treated with local radiotherapy, while seven patients received a combination of radiotherapy and chemotherapy or thalidomide, and two patients received chemotherapy alone with or without thalidomide. The recipient of alloBMT was initially treated with VAD-chemotherapy and local radiotherapy followed by a mini-allograft from the original donor. Eleven patients died at a median of 10 months following diagnosis of the plasmacytoma. Four are still alive, 12-20 months post-plasmacytoma diagnosis. These cases of unconventional disease recurrence are likely to be seen due to sub-clinical seeding of tumour cells suggestive of the presence of an extramedullary (EM) clone of plasma cells with a high degree of chemoresistance. We also review all the available data in the literature for the optimal therapy for patients with isolated EM relapse. C1 Hammersmith Hosp, Imperial Coll London, Fac Med, Dept Haematol, London W12 0NN, England. NHLBI, Stem Cell Allotransplantat Sect, Haematol Branch, NIH, Bethesda, MD 20892 USA. Wolverhampton Gen Hosp, Dept Haematol, Wolverhampton, W Midlands, England. N Hampshire Hosp, Dept Haematol, Basingstoke, Hants, England. Warwick Hosp, Dept Haematol, Warwick, England. Bristol Royal Infirm & Gen Hosp, Dept Haematol, Bristol, Avon, England. RP Apperley, JF (reprint author), Hammersmith Hosp, Imperial Coll London, Fac Med, Dept Haematol, Du Cane Rd, London W12 0NN, England. EM j.apperley@imperial.ac.uk NR 38 TC 40 Z9 43 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0902-4441 J9 EUR J HAEMATOL JI Eur. J. Haematol. PD NOV PY 2005 VL 75 IS 5 BP 376 EP 383 DI 10.1111/j.1600-0609.2005.00531.x PG 8 WC Hematology SC Hematology GA 968MN UT WOS:000232166700003 PM 16191086 ER PT J AU Hakim, FT Gress, RE AF Hakim, FT Gress, RE TI Reconstitution of the lymphocyte compartment after lymphocyte depletion: A key issue in clinical immunology SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Editorial Material DE cytokines; homeostasis; immune deficiency ID STEM-CELL TRANSPLANTATION; REGULATORY T-CELLS; HOMEOSTATIC PROLIFERATION; MULTIPLE-SCLEROSIS; THYMIC OUTPUT; AUTOIMMUNITY; REPERTOIRE; EXPANSION; ADULTS; CHEMOTHERAPY AB Loss of existing T cell populations is a significant clinical problem following cytoreductive therapies or in disease states such as HIV. Characterization of the pathways of T cell regeneration, their limitations and regulation, is central to the development of new approaches for the correction of T cell lymphopenia. Recently, there has been an increasing appreciation that subsets of T cells differ not only in requirements for homeostasis, but in the mechanisms of initial generation and later reconstitution of lost populations. In this issue, Cox et al. determine that variations in cytokine/chemokine levels may affect the biology of T cell recovery which impacts on the development of treatment strategies for lymphopenia. C1 NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Hakim, FT (reprint author), NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. EM fhakim@helix.nih.gov NR 26 TC 20 Z9 22 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 NOV PY 2005 VL 35 IS 11 BP 3099 EP 3102 DI 10.1002/eji.200535385 PG 4 WC Immunology SC Immunology GA 987MQ UT WOS:000233522400003 PM 16231288 ER PT J AU Itoh, Y Wang, Z Ishida, H Eichelberg, K Fujimoto, N Makino, J Ogasawara, K Germain, RN AF Itoh, Y Wang, Z Ishida, H Eichelberg, K Fujimoto, N Makino, J Ogasawara, K Germain, RN TI Decreased CD4 expression by polarized T helper 2 cells contributes to suboptimal TCR-induced phosphorylation and reduced Ca2+ signaling SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE Th1/Th2 cells; T cell receptors; signal transduction; cytokines; protein kinases/phosphatases ID PROTEIN-TYROSINE KINASES; MHC MOLECULE LIGANDS; T-CELLS; IL-4 PRODUCTION; PARTIAL AGONISTS; RECEPTOR LIGAND; GENE-EXPRESSION; TH2 CELLS; TRANSDUCTION; ANERGY AB Polarized Th1 and Th2 cells expressing the same TCR produce distinct biochemical responses to ligand engagement. Compared to Th1 cells, Th2 cells show altered substrate tyrosine phosphorylation and a diminished or transient Ca2+ response. Here we demonstrate that agonist stimulation of Th1 cells leads to the predominant appearance of fully phosphorylated (p23) TCR zeta, substantial phosphorylation of zeta- associated protein 70 (ZAP-70), and strong elevation of intracellular Ca2+, whereas agonist stimulation of Th2 cells expressing an identical TCR results in an elevated p21:p23 TCR zeta ratio, little or no detectable ZAP-70 phosphorylation, and a more limited elevation in intracellular Ca2+. Th2 cells consistently had twofold lower surface CD4 expression as compared to Th1 cells with the same TCR. When CD4 levels in Th2 cells were raised to Th1 levels using retroviral gene transfer, the transduced cells showed greater generation of p23 phospho-zeta, measurable phosphorylation of ZAP-70, and increased Ca2+ responses. These findings suggest that the apparent qualitative differences in TCR signaling characterizing Th1 versus Th2 cells are largely the result of modest quantitative variation in CD4 expression, with decreased CD4 expression playing a significant role in attenuating the proximal signaling responsiveness of Th2 cells to TCR ligands. C1 NIAID, Lymphocyte Biol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. Shiga Univ Med Sci, Dept Pathol, Shiga, Japan. Shiga Univ Med Sci, Dept Dermatol, Shiga, Japan. Shiga Univ Med Sci, Dept Internal Med, Shiga, Japan. RP Germain, RN (reprint author), NIAID, Lymphocyte Biol Sect, Immunol Lab, NIH, Bldg 10 Rm 11N311,10 Ctr Dr MSC-1892, Bethesda, MD 20892 USA. EM rgermain@nih.gov FU Intramural NIH HHS; NIAID NIH HHS [Z01 AI000758-08] NR 37 TC 12 Z9 12 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 NOV PY 2005 VL 35 IS 11 BP 3187 EP 3195 DI 10.1002/eji.200526064 PG 9 WC Immunology SC Immunology GA 987MQ UT WOS:000233522400012 PM 16276482 ER PT J AU Izquierdo, A Murray, EA AF Izquierdo, A Murray, EA TI Opposing effects of amygdala and orbital prefrontal cortex lesions on the extinction of instrumental responding in macaque monkeys SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE emotion; frustration; inhibitory control; perseveration; reversal learning ID AUDITORY SECONDARY REINFORCEMENT; RHESUS-MONKEYS; BASOLATERAL AMYGDALA; ORBITOFRONTAL CORTEX; EMOTIONAL RESPONSES; NEUROTOXIC LESIONS; UNILATERAL LESIONS; PRIMATE AMYGDALA; LIMBIC LESIONS; FRONTAL-CORTEX AB Extinction is a well-known behavioural phenomenon that allows organisms to respond flexibly to a changing environment. Although recent work implicates the amygdala and orbital prefrontal cortex (PFo) in extinction of Pavlovian conditioned fear and aversion, much less is known about the neural bases of instrumental extinction. To explore the contribution of the macaque amygdala to flexible responding in the face of changing reward contingency, we tested the effects of selective, excitotoxic lesions of the amygdala on extinction of an instrumental response. For comparison, we evaluated the effects of ablation of PFo on the same task. Amygdala lesions facilitated the extinction of instrumental responses, whereas lesions of PFo had the opposite effect. C1 NIMH, Sect Neurobiol Learning & Memory, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA. RP Murray, EA (reprint author), NIMH, Sect Neurobiol Learning & Memory, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA. EM murraye@mail.nih.gov OI Murray, Elisabeth/0000-0003-1450-1642 FU Intramural NIH HHS NR 41 TC 71 Z9 71 U1 4 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD NOV PY 2005 VL 22 IS 9 BP 2341 EP 2346 DI 10.1111/j.1460-9568.2005.04434.x PG 6 WC Neurosciences SC Neurosciences & Neurology GA 979XN UT WOS:000232978500022 PM 16262672 ER PT J AU Hoffman, AF Macgill, AM Smith, D Oz, M Lupica, CR AF Hoffman, AF Macgill, AM Smith, D Oz, M Lupica, CR TI Species and strain differences in the expression of a novel glutamate-modulating cannabinoid receptor in the rodent hippocampus SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE C57BL mouse; CB1 cannabinoid receptor; CD1 mouse; electrophysiology; knockout; Sprague Dawley rat ID LONG-TERM POTENTIATION; SYNAPTIC-TRANSMISSION; RAT HIPPOCAMPUS; KNOCKOUT MICE; INHIBITION; INTERNEURONS; MECHANISMS AB A novel, non-CB1 cannabinoid receptor has been defined by the persistence of inhibition of glutamatergic EPSPs by the cannabinoid receptor agonist WIN55,212-2 in mice lacking the cloned CB1 receptor (CB1(-/-)) (Hajos et al., 2001). This novel receptor was also distinguished from CB1 by its sensitivity to the antagonist SR141716A and its insensitivity to the antagonist AM251 (Hajos & Freund, 2002). We have chosen to refer to this putative receptor as CBsc due to its identification on Schaffer collateral axon terminals in the hippocampus. We examined properties of CBsc receptors in Sprague Dawley (SD) rats and two strains of wild-type (WT) mice (C57BL/6J and CD1) used as backgrounds for two independent lines of CB1(-/-) mice (Ledent et al., 1999; Zimmer et al., 1999). The inhibition of synaptic glutamate release by WIN55,212-2 was observed in hippocampal slices from WT CD1 mice and SD rats but was absent in WT C57 mice. We also found that AM251 and SR141716A antagonized the effect of WIN55,212-2 in hippocampal slices from CD1 mice and SD rats demonstrating a lack of selectivity of these ligands for CB1 and CBsc receptors in these animals. The results indicate that the glutamate-modulating CBsc cannabinoid receptor is present in the hippocampi of CD1 mice and SD rats but not in C57BL/6J mice. Thus, we have identified animal models that may permit the study of cannabinoids independently of the novel CBsc receptor (C57(CB1+/+)), the CBsc receptor independently of the cloned CB1 receptor (CD1(CB1-/-)), or in the absence of both receptors (C57(CB1-/-)). C1 NIDA, Neurophysiol Sect, Cellular Neurobiol Branch, Intramural Res Program,NIH,Dept HHS, Baltimore, MD 21224 USA. Oberlin Coll, Dept Neurosci, Oberlin, OH 44074 USA. RP Lupica, CR (reprint author), NIDA, Neurophysiol Sect, Cellular Neurobiol Branch, Intramural Res Program,NIH,Dept HHS, POB 5180, Baltimore, MD 21224 USA. EM clupica@intra.nida.nih.gov RI Oz, Murat/E-2148-2012; Hoffman, Alexander/H-3035-2012 OI Hoffman, Alexander/0000-0002-2676-0628 FU Intramural NIH HHS; NIDA NIH HHS [Z01 DA000457-04] NR 21 TC 43 Z9 45 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD NOV PY 2005 VL 22 IS 9 BP 2387 EP 2391 DI 10.1111/j.1460-9568.2005.04401.x PG 5 WC Neurosciences SC Neurosciences & Neurology GA 979XN UT WOS:000232978500028 PM 16262678 ER PT J AU Mohedano-Moriano, A Martinez-Marcos, A Munoz, M Arroyo-Jimenez, MM Marcos, P Artacho-Perula, E Blaizot, X Insausti, R AF Mohedano-Moriano, A Martinez-Marcos, A Munoz, M Arroyo-Jimenez, MM Marcos, P Artacho-Perula, E Blaizot, X Insausti, R TI Reciprocal connections between olfactory structures and the cortex of the rostral superior temporal sulcus in the Macaca fascicularis monkey SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE association cortex; neuroanatomy; nonhuman primate; olfactory cortex; rostral temporal lobe ID CORTICAL AFFERENT INPUT; RHESUS-MONKEY; MACAQUE MONKEY; ENTORHINAL CORTEX; VISUAL AREA; FUNCTIONAL-PROPERTIES; FRONTAL-CORTEX; PROJECTIONS; ORGANIZATION; NEURONS AB Convergence of sensory modalities in the nonhuman primate cerebral cortex is still poorly understood. We present an anatomical tracing study in which polysensory association cortex located at the fundus and upper bank of the rostral superior temporal sulcus presents reciprocal connections with primary olfactory structures. At the same time, projections from this polysensory area reach multiple primary olfactory centres. Retrograde (Fast Blue) and anterograde (biotinylated dextran-amine and H-3-amino acids) tracers were injected into primary olfactory structures and rostral superior temporal sulcus. Retrograde tracers restricted to the anterior olfactory nucleus resulted in labelled neurons in the rostral portion of the upper bank and fundus of superior temporal sulcus. Injections of biotinylated dextran-amine at the fundus and upper bank of the superior temporal sulcus confirmed this projection by labelling axons in the dorsal and lateral portions of the anterior olfactory nucleus, as well as piriform, periamygdaloid and entorhinal cortices. Retrograde tracer injections at the rostral superior temporal sulcus resulted in neuronal labelling in the anterior olfactory nucleus, piriform, periamygdaloid and entorhinal cortices, thus providing confirmation of the reciprocity between primary olfactory structures and the cortex at the rostral superior temporal sulcus. The reciprocal connections between the rostral part of superior temporal sulcus and primary olfactory structures represent a convergence for olfactory and other sensory modalities at the cortex of the rostral temporal lobe. C1 Univ Castilla La Mancha, Sch Med, Dept Hlth Sci, Human Neuroanat Lab, Albacete 02006, Spain. Univ Castilla La Mancha, CRIB, Albacete 02006, Spain. NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA. RP Insausti, R (reprint author), Univ Castilla La Mancha, Sch Med, Dept Hlth Sci, Human Neuroanat Lab, Avda de Almansa S-N, Albacete 02006, Spain. EM ricardo.insausti@uclm.es RI Munoz, Monica/C-9189-2009; MARTINEZ-MARCOS, ALINO/L-5127-2014; Munoz-Lopez, Monica/F-3154-2016; Mohedano-Moriano, Alicia/L-1121-2016; OI MARTINEZ-MARCOS, ALINO/0000-0003-3691-3605; Mohedano-Moriano, Alicia/0000-0003-4904-6774; Munoz Lopez, Monica/0000-0002-5530-2394; Marcos Rabal, Maria del Pilar/0000-0001-6303-1654 NR 59 TC 16 Z9 16 U1 2 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD NOV PY 2005 VL 22 IS 10 BP 2503 EP 2518 DI 10.1111/j.1460-9568.2005.04443.x PG 16 WC Neurosciences SC Neurosciences & Neurology GA 987JG UT WOS:000233513600012 PM 16307593 ER PT J AU Aggleton, JP Vann, SD Saunders, RC AF Aggleton, JP Vann, SD Saunders, RC TI Projections from the hippocampal region to the mammillary bodies in macaque monkeys SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE entorhinal cortex; fornix; hippocampus; hypothalamus; memory; subiculum; temporal lobe ID HORSERADISH-PEROXIDASE; FORNIX SYSTEM; MACACA-FASCICULARIS; ENTORHINAL CORTEX; CYTOARCHITECTONIC ORGANIZATION; POSTERIOR HYPOTHALAMUS; EFFERENT CONNECTIONS; CORTICAL AFFERENTS; PREFRONTAL CORTEX; SQUIRREL-MONKEY AB A combination of anterograde and retrograde tracers mapped the direct hippocampal and parahippocampal inputs to the mammillary bodies in two species of macaque monkey. Dense projections arose from pyramidal cells in layer III of the subiculum and prosubiculum, and terminated in the medial mammillary nucleus. While there was no evidence of an input from the dentate gyrus or fields CA1-3, a small contribution arose from the presubiculum and entorhinal cortices. All of the hippocampal and parahippocampal projections to the mammillary bodies appeared to use the fornix as a route. The caudal portions of the subiculum and prosubiculum contained the greatest numbers of cells projecting to the mammillary bodies. A light contralateral projection to the medial mammillary nucleus was also observed, although this appeared to arise primarily from the more rostral portions of the subiculum and prosubiculum. There was a crude topography within the medial mammillary nucleus, with the caudal subicular projections terminating in the mid and dorsal portions of the nucleus while the rostral subicular and entorhinal projections terminated in the ventral and lateral portions of the medial nucleus. Light ipsilateral projections throughout the lateral mammillary nucleus were sometimes observed. Comparisons with related studies of the macaque brain showed that the dense hippocampal projections to the mammillary bodies arise from a population of subicular cells separate from those that project to the anterior thalamic nuclei, even though the major output from the mammillary bodies is to the anterior thalamic nuclei. Other comparisons revealed underlying similarities with the corresponding projections in the rat brain. C1 Cardiff Univ, Sch Psychol, Cardiff CF10 3AT, S Glam, Wales. NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA. RP Aggleton, JP (reprint author), Cardiff Univ, Sch Psychol, Tower Bldg,Pk Pl, Cardiff CF10 3AT, S Glam, Wales. EM aggleton@cf.ac.uk RI Vann, Seralynne/A-1601-2010; OI Vann, Seralynne/0000-0002-6709-8773; Aggleton, John/0000-0002-5573-1308 NR 51 TC 49 Z9 49 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD NOV PY 2005 VL 22 IS 10 BP 2519 EP 2530 DI 10.1111/j.1460-9568.2005.04450.x PG 12 WC Neurosciences SC Neurosciences & Neurology GA 987JG UT WOS:000233513600013 PM 16307594 ER PT J AU Rossi, PG Beccaro, M Miccinesi, G Borgia, P Montella, M Costantini, M AF Rossi, PG Beccaro, M Miccinesi, G Borgia, P Montella, M Costantini, M CA ISDOC Working Grp TI Dying of cancer: the impact on the family - an Italian mortality follow-back survey, 2002-2003 SO EUROPEAN JOURNAL OF PUBLIC HEALTH LA English DT Meeting Abstract C1 Agcy Publ Hlth, Reg Lazio, Rome, Italy. Natl Canc Inst, Genoa, Italy. Ctr Studio & Prevenz Oncol, I-50131 Florence, Italy. Natl Canc Inst, Naples, Italy. EM giorgirossi@asplazio.it RI Pisanti, Renato/G-6232-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1101-1262 J9 EUR J PUBLIC HEALTH JI Eur. J. Public Health PD NOV PY 2005 VL 15 SU 1 BP 52 EP 52 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 001UI UT WOS:000234567800127 ER PT J AU Fan, J Heller, NM Gorospe, M Atasoy, U Stellato, C AF Fan, J Heller, NM Gorospe, M Atasoy, U Stellato, C TI The role of post-transcriptional regulation in chemokine gene expression in inflammation and allergy SO EUROPEAN RESPIRATORY JOURNAL LA English DT Review DE allergy; chemokines; inflammation; post-transcriptional regulation; RNA stability ID MESSENGER-RNA STABILITY; ACTIVATED PROTEIN-KINASE; AU-RICH ELEMENT; TUMOR-NECROSIS-FACTOR; 3' UNTRANSLATED REGION; AIRWAY EPITHELIAL-CELLS; MONOCYTE CHEMOATTRACTANT PROTEIN-3; ELAV-LIKE PROTEIN; NF-KAPPA-B; BINDING-PROTEIN AB The aim of this review is to discuss recent advances in the understanding of the regulation of chemokine expression occurring during chronic inflammatory conditions, such as allergic diseases. The focus will be on current data, which suggest that post-transcriptional regulation plays a larger role in chemokine gene regulation than previously recognised. In particular, a growing body of data indicates that mechanisms controlling mRNA stability may be relevant in determining, or maintaining, the increased levels of chemokine gene expression in this context. Such regulatory pathways may be important targets of novel anti-inflammatory strategies. C1 Johns Hopkins Univ, Div Clin Immunol & Allergy, Baltimore, MD USA. NIA, NIH, Baltimore, MD 21224 USA. Univ Missouri, Dept Surg Mol Mircobiol & Immunol, Columbia, MO USA. RP Stellato, C (reprint author), John Hopkins Asthma & Allergy, 5501 Hopkins Bayview Circle, Baltimore, MD 21224 USA. EM stellato@jhmi.edu RI Stellato, Cristiana/P-3001-2015 OI Stellato, Cristiana/0000-0002-1294-8355 FU NIAID NIH HHS [AI 060990-01A1, AI-44242-01A2] NR 137 TC 69 Z9 71 U1 1 U2 3 PU EUROPEAN RESPIRATORY SOC JOURNALS LTD PI SHEFFIELD PA 146 WEST ST, STE 2.4, HUTTONS BLDG, SHEFFIELD S1 4ES, ENGLAND SN 0903-1936 J9 EUR RESPIR J JI Eur. Resp. J. PD NOV PY 2005 VL 26 IS 5 BP 933 EP 947 DI 10.1183/09031936.05.00120204 PG 15 WC Respiratory System SC Respiratory System GA 983IH UT WOS:000233224400027 PM 16264057 ER PT J AU Houle, CD Peddada, SD McAllister, KA Ward, T Malphurs, J Gersch, WD Davis, BJ AF Houle, CD Peddada, SD McAllister, KA Ward, T Malphurs, J Gersch, WD Davis, BJ TI Mutant Brca2/p53 mice exhibit altered radiation responses in the developing mammary gland SO EXPERIMENTAL AND TOXICOLOGIC PATHOLOGY LA English DT Article DE Brca2; p53; apoptosis; proliferation; radiation ID BREAST-CANCER; IONIZING-RADIATION; IN-VIVO; HOMOLOGOUS RECOMBINATION; CELL-CYCLE; GAMMA-IRRADIATION; INDUCED APOPTOSIS; TP53 MUTATIONS; MOUSE MODEL; DNA-BINDING AB Appropriate balance between proliferation and apoptosis is critical for mammary gland development and is often altered during tumorigenesis. Carcinogens like radiation induce DNA damage and activate protective responses such as cell cycle arrest and apoptosis. We used mice carrying Brea2(-/-) and/or p53(-/-) mutations to evaluate the individual and combined effects of these genes on cell proliferation and apoptosis in the developing mammary gland. Mice were exposed to 5 Gy of radiation or chamber exposure (controls) followed by injection with BrdU. Mammary glands were collected 6 h post-radiation exposure and evaluated for proliferation (BrdU) and apoptosis (TUNEL) in terminal end buds (TEB) and ducts. Under control conditions, the Brca2 mutation reduced proliferation and apoptosis in TEB but not ducts, whereas the p53 mutation reduced apoptosis in TEB and ducts but did not influence proliferation. Despite these alterations in proliferation and/or apoptosis, neither mutation, either individually or combined, significantly altered the overall balance between the two as measured by the proliferation to apoptosis ratio (growth index). Following irradiation, the Brca2 mutation had no significant effect on proliferation or apoptosis, whereas the p53 mutation resulted in reduced apoptosis in TEB and ducts but did not significantly influence proliferation. Neither mutation by itself altered the growth index in the TEB after irradiation although combined Brca2/p53 mutation caused significantly increased proliferation, reduced apoptosis, and an elevated growth index in TEB and ducts. These results reveal both independent and collaborative growth regulatory roles for Brca2 and p53 under normal and adverse environmental conditions. Additionally, we demonstrate the importance of gene-environment interactions by showing that Brca2- and p53-deficient mice can compensate for their genetic deficiencies under control conditions but not after exposure to radiation. We also demonstrate distinct spatial differences in the cellular functions of Brca2 and p53 and show that combined mutation of both genes is more detrimental than loss of either gene alone. Published by Elsevier GmbH. C1 Natl Inst Environm Hlth Sci, Lab Womens Hlth, NIH, Res Triangle Pk, NC 27709 USA. N Carolina State Univ, Coll Vet Med, Raleigh, NC 27606 USA. Natl Inst Environm Hlth Sci, Biostat Branch, NIH, Res Triangle Pk, NC 27709 USA. RP Houle, CD (reprint author), Expt Pathol Labs Inc, POB 12766, Res Triangle Pk, NC 27709 USA. EM choule@epl-inc.com RI Peddada, Shyamal/D-1278-2012 NR 58 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER GMBH, URBAN & FISCHER VERLAG PI JENA PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY SN 0940-2993 J9 EXP TOXICOL PATHOL JI Exp. Toxicol. Pathol. PD NOV PY 2005 VL 57 IS 2 BP 105 EP 115 DI 10.1016/j.etp.2005.06.001 PG 11 WC Pathology; Toxicology SC Pathology; Toxicology GA 989JB UT WOS:000233667600003 PM 16325521 ER PT J AU Saunders, RC Mishkin, M Aggleton, JP AF Saunders, RC Mishkin, M Aggleton, JP TI Projections from the entorhinal cortex, perirhinal cortex, presubiculum, and parasubiculum to the medial thalamus in macaque monkeys: identifying different pathways using disconnection techniques SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE anterior thalamic nuclei; lateral dorsal thalamic nucleus; fornix; hippocampus; subiculum; thalamus ID LASTING MEMORY IMPAIRMENT; IN-PLACE MEMORY; HIPPOCAMPAL-FORMATION; PARAHIPPOCAMPAL CORTICES; VISUAL RECOGNITION; RHESUS-MONKEYS; EFFERENT PROJECTIONS; ANTEROGRADE AMNESIA; NEUROTOXIC LESIONS; TEMPORAL CORTEX AB The projections from the perirhinal cortex, entorhinal cortex, parasubiculum, and presubiculum to the thalamus were examined using both anterograde and retrograde tracers. Attention focused on the routes taken by these projections, which were delineated by combining surgical tract section with the placement of a tracer. Projections to the anterior thalamic nuclei almost exclusively used the fornix. These relatively light projections, which arose from all areas of the entorhinal cortex, from the presubiculum, parasubiculum, and area 35 of the perirhinal cortex, terminated mainly in the anterior ventral nucleus. In contrast, the projections to the lateral dorsal nucleus from the entorhinal cortex, presubiculum and parasubiculum were denser than those to the anterior thalamic nuclei. The projections to the lateral dorsal nucleus used two routes. While nearly all of the projections from the subicular complex used the fornix, many of the entorhinal cortex projections passed caudally in the temporopulvinar bundle to reach the lateral dorsal nucleus. The perirhinal cortex, as well as the entorhinal cortex, also projects to nucleus medialis dorsalis. These projections exclusively used the external capsule and thence the inferior thalamic peduncle. Other temporal-thalamic projections included those to the medial pulvinar, via the temporopulvinar bundle, from the perirhinal and entorhinal cortices, and those to the paraventricular nucleus from the entorhinal cortex. By identifying these routes, it is possible to appreciate how different lesions might disconnect temporal-diencephalic pathways and so contribute to memory disorders. C1 Cardiff Univ, Sch Psychol, Cardiff CF10 3AT, S Glam, Wales. NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA. RP Aggleton, JP (reprint author), Cardiff Univ, Sch Psychol, Pk Pl, Cardiff CF10 3AT, S Glam, Wales. EM aggleton@cf.ac.uk OI Aggleton, John/0000-0002-5573-1308 NR 73 TC 56 Z9 57 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD NOV PY 2005 VL 167 IS 1 BP 1 EP 16 DI 10.1007/s00221-005-2361-3 PG 16 WC Neurosciences SC Neurosciences & Neurology GA 980NA UT WOS:000233024000001 PM 16143859 ER PT J AU Wechselberger, C Bianco, C Strizzi, L Ebert, AD Kenney, N Sun, YP Salomon, DS AF Wechselberger, C Bianco, C Strizzi, L Ebert, AD Kenney, N Sun, YP Salomon, DS TI Modulation of TGF-beta signaling by EGF-CFC proteins SO EXPERIMENTAL CELL RESEARCH LA English DT Review DE TGF-beta; EGF-CFC proteins; cripto-1; apoptosis; cancer; signal transduction cascades ID MAMMARY EPITHELIAL-CELLS; CERVICAL-CARCINOMA CELLS; HUMAN BREAST CARCINOMAS; GROWTH-FACTOR-ALPHA; TRANSGENIC MICE; GLAND DEVELOPMENT; HUMAN CRIPTO-1; VERTEBRATE DEVELOPMENT; CANCER CELLS; LIPID RAFTS AB Members of the transforming growth factor-beta (TGF-beta) family of ligands exhibit potent growth-suppressive and/or apoptosis-inducing effects on different types of cells. They perform essential roles in the elimination of damaged or abnormal cells from healthy tissues. On the other hand, TGF-beta s have also been shown to act as tumor-promoting cytokines in a number of malignancies that are capable of stimulating extracellular matrix production, cell migration, invasion, angiogenesis, and immune suppression. Dissecting the complex, multifaceted roles of different TGF-beta-related peptides especially during the development of pathological conditions and in carcinogenesis is an area of continuous research and development. The characterization of EGF-CFC proteins as essential co-receptors that contribute to the modulation of the physiological activities of some of the TGF-beta ligands will be beneficial for future medical research and the adaptation and possible readjustment of currently applied therapeutic regimes. (c) 2005 Elsevier Inc. All rights reserved. C1 Upper Austrian Res GmbH, Ctr Biomed Nanotechnol, A-4020 Linz, Austria. NIH, Tumor Growth Factor Sect, Mammary Biol & Tumorigenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA. Dept Gynecol, Charite, D-12200 Berlin, Germany. Hampton Univ, Dept Biol Sci, Hampton, VA 23668 USA. RP Wechselberger, C (reprint author), Upper Austrian Res GmbH, Ctr Biomed Nanotechnol, Scharitzerstr 6-8,4th Floor, A-4020 Linz, Austria. EM christian.wechselberger@uar.at NR 73 TC 4 Z9 4 U1 1 U2 1 PU ELSEVIER INC PI SAN DIEGO PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495, UNITED STATES SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD NOV 1 PY 2005 VL 310 IS 2 BP 249 EP 255 DI 10.1016/j.yexcr.2005.07.023 PG 7 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 980DA UT WOS:000232992900001 PM 16137677 ER PT J AU Dixit, VD Taub, DD AF Dixit, VD Taub, DD TI Ghrelin and immunity: A young player in an old field SO EXPERIMENTAL GERONTOLOGY LA English DT Review DE ghrelin; GHS-R; inflammation; thymus; cytokines; IL-6; frailty; aging ID GROWTH-HORMONE SECRETAGOGUE; CHRONIC HEART-FAILURE; LEFT-VENTRICULAR DYSFUNCTION; REGULATES BONE-FORMATION; AGOUTI-RELATED PROTEIN; T-CELL DEVELOPMENT; PLASMA GHRELIN; FOOD-INTAKE; ISCHEMIA/REPERFUSION INJURY; DILATED CARDIOMYOPATHY AB There is increasing evidence of the coupling of immune status to the metabolic system. The communication between the state of systemic and cellular energy balance to immune compartment is mediated via a complex array of cytokines, hormones and neuropeptides. Ghrelin, a recently described orexigenic peptide hormone, is predominantly produced by the stomach and functions as a positive regulator of the somatotropic axis and a peripheral signal of negative energy balance. Apart from its well-studied metabolic effects, ghrelin also exerts multiple regulatory effects on several other organ systems including the cardiovascular, central nervous and immune systems. Here, we summarize the growing evidence of ghrelin as a significant player in the regulation of inflamtnation and the immune function and the potential therapeutic targeting of ghrelin or its receptor, the growth hormone secretagogue receptor (GHS-R), in various inflammatory and cachexic disease states. Published by Elsevier Inc. C1 US HHS Natl Inst Hlth, Gerontol Res Ctr, Immunol Lab, Clin Immunol Sect,Intramural Res Program, Baltimore, MD 21224 USA. RP Taub, DD (reprint author), US HHS Natl Inst Hlth, Gerontol Res Ctr, Immunol Lab, Clin Immunol Sect,Intramural Res Program, 5600 Nathan Shock Dr,Box 21, Baltimore, MD 21224 USA. EM dixitvd@grc.nia.nih.gov; taubd@grc.nia.nih.gov NR 117 TC 60 Z9 69 U1 1 U2 3 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 NOV PY 2005 VL 40 IS 11 BP 900 EP 910 DI 10.1016/j.exger.2005.09.003 PG 11 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 985YJ UT WOS:000233414500010 PM 16233968 ER PT J AU Kashyap, M Bailey, DP Gomez, G Rivera, J Huff, TF Ryan, JJ AF Kashyap, M Bailey, DP Gomez, G Rivera, J Huff, TF Ryan, JJ TI TGF-beta(1) inhibits late-stage mast cell maturation SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID GROWTH-FACTOR-BETA; TUMOR-NECROSIS-FACTOR; FC-EPSILON-RI; BONE-MARROW; TGF-BETA; DIFFERENTIATION; PROLIFERATION; EXPRESSION; RECEPTOR; RELEASE AB Objective. The objective of this study was to determine the effects of transforming growth factor (TGF)-beta(1), on mast cell development. Materials and Methods. Mast cells were cultured from mouse bone marrow in interleukin (IL)-3 + stem cell factor, in the presence or absence of TGF-beta(1). We assessed mast cell development by measuring the expression of kit, T1/ST2, Fc epsilon RI, and Fc gamma receptors. Cell morphology was determined by histochemical staining. Alterations in Fc epsilon RI subunit expression were measured by Western blot analysis. Adoptive transfer of cultured mast cells into mast cell-deficient W/W-v mice was used to determine if the in vivo environment could reverse the inhibitory effects of TGF-beta(1). Results. TGF-beta(1) decreased Fc epsilon RI, c-kit, T1/ST2, and Fc gamma R expression, and inhibited granule formation in developing mast cells. Accessory cells were not required for this inhibition. Smad3 deficiency did not alter the response of bone marrow cells to TGF-beta(1). TGF-beta(1) inhibited expression of the Fc epsilon RI alpha subunit protein, without decreasing beta or gamma proteins. Mast cells derived in the presence of TGF-beta 1 were functionally impaired, as IgE-mediated cytokine secretion was greatly reduced. The changes in granule formation and surface antigen expression were long-standing, as they were not reversed by transfer to W/W-v mice. Conclusions. TGF beta(1) may contribute to mast cell homeostasis by inhibiting maturation from bone marrow precursors. The effects of TGF-beta(1) result in greatly diminished expression of cell surface markers, reduced granulation, and lack of responsiveness to IgE-mediated activation. Thus TGF-beta(1) can serve as a potent and multifunctional regulator of mast cell maturation. (c) 2005 International Society for Experimental Hematology. Published by Elsevier Inc. C1 Virginia Commonwealth Univ, Dept Biol, Richmond, VA 23284 USA. NIAMSD, Mol Inflammat Sect, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA. RP Ryan, JJ (reprint author), Virginia Commonwealth Univ, Dept Biol, Box 842012, Richmond, VA 23284 USA. EM jjryan@saturn.vcu.edu RI Kashyap, Mohit/F-4534-2011 FU NCI NIH HHS [1R01CA91839]; NIAID NIH HHS [1R01AI43433] NR 44 TC 20 Z9 20 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 NOV PY 2005 VL 33 IS 11 BP 1281 EP 1291 DI 10.1016/j.exphem.2005.07.001 PG 11 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 989ZV UT WOS:000233713800005 PM 16263412 ER PT J AU Drutskaya, MS Ortiz, M Liepinsh, DJ Kuprash, DV Nedospasov, SA Keller, JR AF Drutskaya, MS Ortiz, M Liepinsh, DJ Kuprash, DV Nedospasov, SA Keller, JR TI Inhibitory effects of tumor necrosis factor on hematopoiesis seen in vitro are translated to increased numbers of both committed and multipotent progenitors in TNF-deficient mice SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID BONE-MARROW CULTURES; STEM-CELL FACTOR; FACTOR-ALPHA; RHEUMATOID-ARTHRITIS; FACTOR-RECEPTOR; PSORIATIC-ARTHRITIS; APLASTIC-ANEMIA; PROLIFERATION; P55; ACTIVATION AB Objectives. The effects of TNF deficiency on myelopoiesis were evaluated in long-term (LTBMC) and short-term bone marrow cultures (STBMC) and compared to hematopoietic activity in vivo in TNF-deficient mice. Methods. LTBMC and STBMC were established from bone marrow of TNF-deficient mice in the presence or absence of soluble TNF. Total cell production was measured over time, as well as the number of colony-forming units in culture (CFU-C). Morphology of nonadherent (NA) cells in LTBMC was assessed after 10 weeks. Bone marrow cells (BMC) and peripheral blood (PB) cells were used to determine lineage distribution within the hematopoietic system. BMC were sorted to obtain Lin(-)c-kit(+)Sca-1(-) and Lin(-)c-kit(+)Sca-1(+) cells, which were plated in semisolid media to determine CFU-C numbers or injected into irradiated recipients to determine colony formation in the spleen (CFU-S). Results. TNF-deficient LTBMC and STBMC show increased proliferative capacity, which can be inhibited by exogenous TNF to wild-type levels. Morphological analysis of NA cells from TNF-deficient LTBMC revealed increased numbers of cells at early stages of granulocytic differentiation (myeloblasts/promyelocytes) paralleled by a sharp decrease in the number of terminally differentiated polymorphonuclear neutrophils. Slightly elevated numbers of leukocytes, mainly neutrophils, were detected in PB of TNF-deficient mice. In. bone marrow of TNF-deficient mice a significant increase in the number of both CFU-GM within Lin(-)c-kit(+)Sca-1(-) population and CFU-S within Lin-c-kit+Sca-l+ population was observed. Conclusions. TNF has inhibitory effects on granulocyte-macrophage progenitors in vitro and on committed and primitive hematopoietic progenitors in vivo. However, in adult organism TNF deficiency is mostly compensated and controlled. (c) 2005 International Society for Experimental Hematology. C1 Russian Acad Sci, Engelhardt Inst Mol Biol, Lab Mol Immunol, Moscow 119991, Russia. Natl Canc Inst, Basic Res Program, SAIC Frederick, Frederick, MD USA. Canc Res Ctr, Mol Immunoregulat Lab, Frederick, MD USA. RP Drutskaya, MS (reprint author), Russian Acad Sci, Engelhardt Inst Mol Biol, Lab Mol Immunol, Moscow 119991, Russia. EM maridru@rol.ru RI Nedospasov, Sergei/J-5936-2013; Nedospasov, Sergei/L-1990-2015; Kuprash, Dmitry/O-4899-2015; Nedospasov, Sergei/Q-7319-2016 OI Kuprash, Dmitry/0000-0002-1488-4148; FU NCI NIH HHS [N01-CO-12400] NR 42 TC 6 Z9 7 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 NOV PY 2005 VL 33 IS 11 BP 1348 EP 1356 DI 10.1016/j.exphem.2005.08.001 PG 9 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 989ZV UT WOS:000233713800012 PM 16263419 ER PT J AU Radley, JJ Rocher, AB Janssen, WGM Hof, PR McEwen, BS Morrison, JH AF Radley, JJ Rocher, AB Janssen, WGM Hof, PR McEwen, BS Morrison, JH TI Reversibility of apical dendritic retraction in the rat medial prefrontal cortex following repeated stress SO EXPERIMENTAL NEUROLOGY LA English DT Article ID CA3 PYRAMIDAL NEURONS; CONDITIONED FEAR; WORKING-MEMORY; PROJECTIONS; ATROPHY; MORPHOLOGY; AMYGDALA; NUCLEUS; REORGANIZATION; EXTINCTION AB Apical dendritic retraction and axospinous synapse loss in the medial prefrontal cortex (PFC) are structural alterations that result from repeated restraint stress. Such changes in this brain region may be associated with impaired working memory, altered emotionality, and inability to regulate hypothalamic-pituitary adrenal activity, which in turn may underlie stress-related mental illnesses. In the present study, we examined the persistence of these stress-induced dendritic alterations in the medial PFC following the cessation of stress. Animals received either daily restraint stress for a 3-week period and were then allowed to recover for another 3 weeks, restraint stress for 3 or 6 weeks, or no restraint. Following perfusion and fixation, intracellular iontophoretic injections of Lucifer Yellow were performed in layer II/III pyramidal neurons in slices from the medial PFC, and apical and basal dendritic arbors were reconstructed in three dimensions. We observed a significant reduction in apical dendritic length and branch number following 3 or 6 weeks of repeated stress compared to 3-week stress/3-week recovery. These results suggest that stress-induced dendritic plasticity in the medial PFC is reversible and may have implications for the functional recovery of medial PFC function following prolonged psychological stress. (c) 2005 Elsevier Inc. All rights reserved. C1 CUNY Mt Sinai Sch Med, Dept Neurosci, New York, NY 10029 USA. Rockefeller Univ, Neuroendocrinol Lab, New York, NY 10021 USA. NIMH, Ctr Fear & Anxiety, New York, NY 10003 USA. RP Radley, JJ (reprint author), Salk Inst Biol Studies, Neuronal Struct & Funct Lab, POB 85800, San Diego, CA 92310 USA. EM radley@salk.edu; john.morrison@mssm.edu RI Morrison, John/F-9229-2012 FU NIMH NIH HHS [MH58911] NR 32 TC 144 Z9 147 U1 0 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD NOV PY 2005 VL 196 IS 1 BP 199 EP 203 DI 10.1016/j.expneurol.2005.07.008 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 976SG UT WOS:000232753000022 PM 16095592 ER PT J AU Berman, J AF Berman, J TI Clinical status of agents being developed for leishmaniasis SO EXPERT OPINION ON INVESTIGATIONAL DRUGS LA English DT Review DE fluconazole; imiquimod; leishmaniasis; miltefosine; paromomycin; sitamaquine ID AMERICAN CUTANEOUS LEISHMANIASIS; INTRALESIONAL MEGLUMINE ANTIMONIATE; AMINOSIDINE PAROMOMYCIN OINTMENT; INDIAN VISCERAL LEISHMANIASIS; DOUBLE-BLIND TRIAL; SODIUM STIBOGLUCONATE; TOPICAL PAROMOMYCIN; ORAL FLUCONAZOLE; KALA-AZAR; COMPASSIONATE USE AB Leishmaniasis, which exists in both visceral and cutaneous forms, is currently treated with intramuscular antimony or intravenous amphotericin B. The primary unmet need is for oral therapy. Of the several drugs in clinical development, miltefosine is unique in being an oral agent with efficacy against both forms of the disease. Sitamaquine is an oral agent with substantial but not sufficient efficacy against visceral disease. oral fluconazole has been shown to be more effective than placebo in one instance: for Leishmania major cutane-disease from Saudi Arabia. Paromomycin is in widespread trial. Topical ous paromomycin formulations are being tested for cutaneous disease, and intramuscular paromomycin is in Phase III trial for Indian visceral disease. The most likely replacements for present therapy are oral miltefosine for many of the visceral and cutaneous syndromes, intramuscular paromomycin for visceral disease and topical paromomycin for some forms of cutaneous disease. C1 Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. RP Berman, J (reprint author), Natl Ctr Complementary & Alternat Med, 6707 Democracy Blvd,Suite 401, Bethesda, MD 20892 USA. EM bermanjo@mail.nih.gov NR 55 TC 34 Z9 34 U1 0 U2 3 PU ASHLEY PUBLICATIONS LTD PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1354-3784 J9 EXPERT OPIN INV DRUG JI Expert Opin. Investig. Drugs PD NOV PY 2005 VL 14 IS 11 BP 1337 EP 1346 DI 10.1517/13543784.14.11.1337 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 982BA UT WOS:000233130500003 PM 16255674 ER PT J AU Schreiner, B Voss, J Wischhusen, JR Dombrowski, Y Steinle, A Lochmuller, H Dalakas, M Melms, A Wiendl, H AF Schreiner, B Voss, J Wischhusen, JR Dombrowski, Y Steinle, A Lochmuller, H Dalakas, M Melms, A Wiendl, H TI Expression of toll-like receptors by human muscle cells in vitro and in vivo: TLR3 is highly expressed in inflammatory and HIV myopathies, mediates IL-8 release, and up-regulation of NKG2D-ligands SO FASEB JOURNAL LA English DT Article DE immunobiology of muscle; TLR; myositis; myoblasts ID DOUBLE-STRANDED-RNA; INCLUSION-BODY MYOSITIS; NF-KAPPA-B; MATRIX METALLOPROTEINASES; DIFFERENTIAL EXPRESSION; MONOCLONAL-ANTIBODY; CYTOKINE EXPRESSION; ADHESION MOLECULES; DUCHENNE DYSTROPHY; ENDOTHELIAL-CELLS AB The particular microenvironment of the skeletal muscle can be the site of complex immune reactions. Toll-like receptors (TLRs) mediate inflammatory stimuli from pathogens and endogenous danger signals and link the innate and adaptive immune system. We investigated innate immune responses in human muscle. Analyzing TLR1-9 mRNA in cultured myoblasts and rhabdomyosarcoma cells, we found constitutive expression of TLR3. The TLR3 ligand Poly (I:C), a synthetic analog of dsRNA, and IFN-gamma increased TLR3 levels. TLR3 was mainly localized intracellularly and regulated at the protein level. Poly (I:C) challenge 1) activated nuclear factor-kappa B (NF-kappa B), 2) increased IL-8 release, and 3) up-regulated NKG2D ligands and NK-cell-mediated lysis of muscle cells. We examined muscle biopsy specimens of 6 HIV patients with inclusion body myositis/polymyositis (IBM/ PM), 7 cases of sporadic IBM and 9 nonmyopathic controls for TLR3 expression. TLR3 mRNA levels were elevated in biopsy specimens from patients with IBM and HIV-myopathies. Muscle fibers in inflammatory myopathies expressed TLR3 in close proximity of infiltrating mononuclear cells. Taken together, our study suggests an important role of TLR3 in the immunobiology of muscle, and has substantial implications for the understanding of the pathogenesis of inflammatory myopathies or therapeutic interventions like vaccinations or gene transfer. C1 Univ Tubingen, Dept Gen Neurol, Hertie Inst Clin Brain Res, Tubingen, Germany. NINDS, NIH, Bethesda, MD 20892 USA. Univ Tubingen, Dept Immunol, Inst Cell Biol, Tubingen, Germany. Univ Munich, Genzentrum, Friedrich Baur Inst, Munich, Germany. Univ Munich, Dept Neurol, Munich, Germany. Univ Wurzburg, Dept Neurol & Gynecol, Wurzburg, Germany. RP Julius Maximilians Univ Wurzburg, Clin Res Grp Multiple Sclerosis & Neuroimmunol, Dept Neurol, Josef Schneider Str 11, D-97080 Wurzburg, Germany. EM heinz.wiendl@klinik.uni-wuerzburg.de RI Steinle, Alexander/E-6131-2012; OI Lochmuller, Hanns/0000-0003-2324-8001; Steinle, Alexander/0000-0001-5081-8503 NR 57 TC 2 Z9 2 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD NOV PY 2005 VL 19 IS 13 BP 118 EP + DI 10.1096/fj.05-4342fje PG 22 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 994TC UT WOS:000234053100009 ER PT J AU Appella, E Anderson, CW AF Appella, E Anderson, CW TI Identifying protein interactions - Experimental approaches SO FEBS JOURNAL LA English DT Editorial Material C1 NCI, Chem Immunol Sect, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. Brookhaven Natl Lab, Dept Biol, Long Isl City, NY USA. RP Appella, E (reprint author), NCI, Chem Immunol Sect, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NR 4 TC 0 Z9 0 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1742-464X J9 FEBS J JI FEBS J. PD NOV PY 2005 VL 272 IS 21 BP 5389 EP 5390 DI 10.1111/j.1742-4658.2005.04969.x PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 976ZM UT WOS:000232772200001 ER PT J AU Houtman, JCD Barda-Saad, M Samelson, LE AF Houtman, JCD Barda-Saad, M Samelson, LE TI Examining multiprotein signaling complexes from all angles - The use of complementary techniques to characterize complex formation at the adapter protein, linker for activation of T cells SO FEBS JOURNAL LA English DT Article; Proceedings Paper CT 15th Biennial Conference on Methods in Protein Structure Analysis CY AUG 29-SEP 02, 2004 CL Seattle, WA SP Int Assoc Protein Structure Anal & Proteom DE LAT; multiprotein complexes; signal transduction; T cells; T cell receptor ID ISOTHERMAL TITRATION CALORIMETRY; FC-EPSILON-RI; PHOSPHOLIPASE C-GAMMA-1 PLC-GAMMA-1; ANTIGEN RECEPTOR; TYROSINE PHOSPHORYLATION; MEDIATED ACTIVATION; SH2 DOMAINS; LAT; BINDING; SLP-76 AB Dynamic protein-protein interactions are involved in most physiological processes and, in particular, for the formation of multiprotein signaling complexes at transmembrane receptors, adapter proteins and effector molecules. Because the unregulated induction of signaling complexes has substantial clinical relevance, the investigation of these complexes is an active area of research. These studies strive to answer questions about the composition and function of multiprotein signaling complexes, along with the molecular mechanisms of their formation. In this review, the adapter protein, linker for activation of T cells (LAT), will be employed as a model to exemplify how signaling complexes are characterized using a range of techniques. The intensive investigation of LAT highlights how the systematic use of complementary techniques leads to an integrated understanding of the formation, composition and function of multiprotein signaling complexes that occur at receptors, adapter proteins and effector molecules. C1 NCI, NIH, Lab Cellular & Mol Biol, Bethesda, MD 20892 USA. RP Samelson, LE (reprint author), NCI, NIH, Lab Cellular & Mol Biol, Bethesda, MD 20892 USA. EM samelson@helix.nih.gov FU Intramural NIH HHS; NCI NIH HHS [Z01 BC010304-07] NR 63 TC 27 Z9 30 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1742-464X J9 FEBS J JI FEBS J. PD NOV PY 2005 VL 272 IS 21 BP 5426 EP 5435 DI 10.1111/j.1742-4658.2005.04972.x PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 976ZM UT WOS:000232772200005 PM 16262684 ER PT J AU Rubinstein, YR Furusawa, T Lim, JH Postnikov, YV West, KL Birger, Y Lee, S Nguyen, P Trepel, JB Bustin, M AF Rubinstein, YR Furusawa, T Lim, JH Postnikov, YV West, KL Birger, Y Lee, S Nguyen, P Trepel, JB Bustin, M TI Chromosomal protein HMGN1 modulates the expression of N-cadherin SO FEBS JOURNAL LA English DT Article DE HMG protein; N-cadherin; chromatin; transcription ID CELL-CELL ADHESION; HIGH-MOBILITY; BETA-CATENIN; HISTONE H1; CHROMATIN; BINDING; CANCER; PHOSPHORYLATION; DIFFERENTIATION; EMBRYOGENESIS AB HMGN1 is a nuclear protein that binds to nucleosomes and alters the accessibility of regulatory factors to their chromatin targets. To elucidate its biological function and identify specific HMGN1 target genes, we generated Hmgn1-/- mice. DNA microarray analysis of Hmgn1+/+ and Hmgn1-/- embryonic fibroblasts identified N-cadherin as a potential HMGN1 gene target. RT-PCR and western blot analysis confirmed a linkage between HMGN1 expression and N-cadherin levels. In both transformed and primary mouse embryonic fibroblasts (MEFs), HMGN1 acted as negative regulator of N-cadherin expression. Likewise, the N-cadherin levels in early embryos of Hmgn1-/- mice were higher than those of their Hmgn1+/+ littermates. Loss of HMGN1 increased the adhesiveness, motility and aggregation potential of Hmgn1-/- MEFs, a phenotype consistent with increased levels of N-cadherin protein. Re-expression of wild-type HMGN1, but not of the mutant HMGN1 protein that does not bind to chromatin, in Hmgn1-/- MEFs, decreased the levels of N-cadherin and restored the Hmgn1+/+ phenotype. These studies demonstrate a role for HMGN1 in the regulation of specific gene expression. We suggest that in MEFs, and during early mouse development, the interaction of HMGN1 with chromatin down-regulates the expression of N-cadherin. C1 NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. Andong Natl Univ, Dept Biol, Gyeongsangbuk Do, South Korea. Univ Glasgow, Western Infirm Pathol, Div Canc Sci & Mol Pathol, Glasgow G12 8QQ, Lanark, Scotland. RP Bustin, M (reprint author), NCI, Lab Metab, NIH, Bldg 37,Room 3122, Bethesda, MD 20892 USA. EM bustin@helix.nih.gov RI Bustin, Michael/G-6155-2015 FU Intramural NIH HHS [Z01 BC004496-30] NR 44 TC 16 Z9 16 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1742-464X J9 FEBS J JI FEBS J. PD NOV PY 2005 VL 272 IS 22 BP 5853 EP 5863 DI 10.1111/j.1742-4658.2005.04980.x PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 982FO UT WOS:000233143600018 PM 16279949 ER PT J AU Hediger, ML Hartnett, HJ Louis, GMB AF Hediger, ML Hartnett, HJ Louis, GMB TI Association of endometriosis with body size and figure SO FERTILITY AND STERILITY LA English DT Article DE body figure; body mass index; endometriosis; fetal origin; silhouette ID MILD ENDOMETRIOSIS; WOMEN; RISK; EPIDEMIOLOGY; DIAGNOSIS; ACCURACY; EXPOSURE; CLASSIFICATION; AUTOIMMUNE; MENARCHE AB Objective: To determine whether body size and perceived figure, both current and historical, are associated with a diagnosis of endometriosis on laparoscopy. Design: Cohort study of consecutively identified patients undergoing laparoscopy for tubal sterilization or as a diagnostic procedure. Setting: Two university-affiliated hospitals. Patient(s): A cohort of 84 women aged 18-40 years. Endometriosis was visualised in 32 cases; 52 women (controls) had no visualized endometriosis, including 22 undergoing tubal sterilization and 30 with other gynecologic pathology. Interventions: None. Main Outcome Measures: Body mass index (BMI, kg/m(2)) from self-report and perception of body figure were compared for their ability to predict case status (diagnosed endometriosis), using logistic regression models. Longitudinal trends in BMI based on perceived figure at 5-year intervals from age 15 years were compared using mixed linear models. Results: Based on self-report, women diagnoses with endometriosis were taller, thinner, and had a significantly lower BMI. In this series, cases were likely to be late maturers (menarche at >= 14 y) and late to initiate sexual activity ( >= 21 y), and they were less likely to be gravid, parous, and a current smoker. Adjusting for age (in years), being tall (height >= 68 in), and parity (yes vs. no), a higher current BMI was statistically protective for a diagnosis of endometriosis, regardless of whether BMI was determined by self-report (adjusted odds ratio [AOR] = 0.88, 95% confidence interval [CI] 0.79-0.99) or from perceived figure (AOR = 0.86, 95% CI 0.75-0.99). For every unit increase in BMI (kg/m(2)), there was an approximate 12%-14% decrease in the liklihood of being diagnosed with endometriosis. In an adjusted repeated measures model, BMI was 21.3 +/- 0.6 kg/m(2) (estimate +/- SE) for women with endometriosis, compared with 23.2 +/- 0.4 kg/m(2) for the controls, a difference over all ages of -1.9 +/- 0.8 kg/m(2.) This is a consistent difference of about 10 lb at every age, assuming an average height of about 64.5 in. Conclusion(s): In a laparoscopy cohort, women diagnosed with endometriosis were found to have a lower BMI (leaner body habits), both at the time of diagnosis and historically. That women diagnosed with endometriosis may have a consistently lean physique during adolescence and young adulthood lends support to the suggestion of there being an in utero or early childhood origin for endometriosis. C1 NICHHD, Div Epidemiol Stat & Prevent Res, Epidemiol Branch, NIH, Bethesda, MD 20892 USA. RP Hediger, ML (reprint author), NICHHD, Div Epidemiol Stat & Prevent Res, Epidemiol Branch, NIH, Bldg 6100,Room 7B03,MSC 7510,9000 Rockville Pike, Bethesda, MD 20892 USA. EM hedigerm@exchange.nih.gov OI Buck Louis, Germaine/0000-0002-1774-4490 FU Intramural NIH HHS; NICHD NIH HHS [Z01 HD008730-05]; NIEHS NIH HHS [ES 0904-01] NR 45 TC 73 Z9 75 U1 1 U2 6 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 NOV PY 2005 VL 84 IS 5 BP 1366 EP 1374 DI 10.1016/j.fertnstert.2005.05.029 PG 9 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 985GO UT WOS:000233365500015 PM 16275231 ER PT J AU Parker, JD Sinaii, N Segars, JH Godoy, H Winkel, C Stratton, P AF Parker, JD Sinaii, N Segars, JH Godoy, H Winkel, C Stratton, P TI Adhesion formation after laparoscopic excision of endometriosis and lysis of adhesions SO FERTILITY AND STERILITY LA English DT Article; Proceedings Paper CT 51st Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 24-27, 2004 CL Houston, TX SP Soc Gynecol Invest DE endometriosis; laser surgery; adhesion formation; chronic pelvic pain ID PERITONEAL ADHESIONS; 2ND-LOOK LAPAROSCOPY; NERVE-FIBERS; SURGERY; PREVENTION; REFORMATION AB Objective: To evaluate adhesion reformation after laparoscopic excision of endometriosis and adhesiolysis in women with chronic pelvic pain. Design: Prospective clinical trial. Setting: University hospital. Patient(s): Thirty-eight women with endometriosis and chronic pelvic pan. Intervention(s): A primary and second-look laparoscopy with adhesiolysis and excision of endometriotic lesions with a neodymium yttrium argon garnet surgical laser technologies (SLT) contact laser. Main Outcome Measure(s): Adhesion formation and character (thin, thin and thick, or think). Location of adhesions at a first laparoscopy was compared with de novo or reformation of adhesions and the location of adhesions at a second surgery. Results(s): Adhesions or adhesions combined with endometriotic lesions were significantly more likely to reform at second surgery compared with sites having only an endometriosis lesion. Thick adhesions were associated with a significantly increased likelihood of an adhesion reforming, compared with thin adhesions or thin and thick adhesions. Lesions or adhesions involving the ovary were more likely to be associated with adhesions at a subsequent surgery, compared with lesions in the adjacent ovarian fossa or fallopian tube. Conclusion(s): Most patients developed adhesions after radical surgical excision of endometriosis for pelvic pain. The high incidence of adhesion formation after surgery for endometriosis underscores the importance of optimizing surgical techniques to potentially reduce adhesion formation. C1 NICHHD, Reprod Biol & Med Branch, NIH, Bethesda, MD 20892 USA. NIH, Combined Fed Fellowship Reprod Endocrinol & Infer, Walter Reed Army Med Ctr, Natl Naval Med Ctr, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bethesda, MD 20814 USA. Georgetown Univ, Med Ctr, Dept Obstet & Gynecol, Washington, DC 20057 USA. RP Stratton, P (reprint author), NICHHD, Reprod Biol & Med Branch, NIH, 10 Ctr Dr MSC1109,Bldg 10 CRC,Room 1-13140, Bethesda, MD 20892 USA. EM ps79c@nih.gov FU Intramural NIH HHS NR 26 TC 31 Z9 31 U1 0 U2 1 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 NOV PY 2005 VL 84 IS 5 BP 1457 EP 1461 DI 10.1016/j.fertnstert.2005.04.057 PG 5 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 985GO UT WOS:000233365500028 PM 16275244 ER PT J AU Pastor, CL Vanderhoof, VH Lim, LCL Calis, KA Premkumar, A Guerrero, NT Nelson, LM AF Pastor, CL Vanderhoof, VH Lim, LCL Calis, KA Premkumar, A Guerrero, NT Nelson, LM TI Pilot study investigating the age-related decline in ovarian function of regularly menstruating normal women SO FERTILITY AND STERILITY LA English DT Article DE ovary; aging; inhibin; Mullerian inhibiting substance; anti-Mullerian hormone; antral follicle count; FSH stimulation ID FOLLICLE-STIMULATING-HORMONE; IN-VITRO FERTILIZATION; ANTI-MULLERIAN HORMONE; CITRATE CHALLENGE TEST; INHIBIN-B; POOR RESPONSE; RESERVE TEST; INVITRO FERTILIZATION; PROVEN FERTILITY; REPRODUCTIVE AGE AB Objective: To use a pilot study to investigate markers of the age-related decline in ovarian function of regularly menstruating normal women. Design: Prospective. Setting: Tertiary research center. Patient(s): Healthy volunteers (n = 42) aged 18 to 50 years who had regular ovulatory menstrual cycles and a prior pregnancy. Interventions(s): A single 300 IU dose of human recombinant FSH on day 3 of the menstrual cycle. Main Outcome Measure(s): Antral follicle count by transvaginal ultrasound and basal and FSH-stimulated serum markers. Results(s): Age correlated most strongly with FSH-stimulated inhibin B (r = -0.660), followed by antral follicle count (r = 0.578), basal FSH (r = 0.509), basal Mullerian inhibin B level had the strongest correlation with age Basal serum MIS level had the strongest correlation with total antral follicle count. We confirm a previous report that in normal women, the antral follicle count as determined by transvaginal ultrasound examination correlates better with age than do basal FSH and Basal inhibin B levels. C1 NICHHD, Sect Womens Hlth Res, Dev Endocrinol Branch, Intramural Res Program, Bethesda, MD 20892 USA. NIH, Clin Res Ctr, Bethesda, MD 20892 USA. Specialty Labs, Santa Monica, CA USA. RP Nelson, LM (reprint author), CRC, Room 1-3330,10 Ctr Dr,MSC-1103, Bethesda, MD 20892 USA. EM lawrence_nelson@nih.gov NR 55 TC 13 Z9 14 U1 0 U2 1 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 NOV PY 2005 VL 84 IS 5 BP 1462 EP 1469 DI 10.1016/j.fertnstert.2005.05.024 PG 8 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 985GO UT WOS:000233365500029 PM 16275245 ER PT J AU Whittaker, P San, RHC Clarke, JJ Seifried, HE Dunkel, VC AF Whittaker, P San, RHC Clarke, JJ Seifried, HE Dunkel, VC TI Mutagenicity of chromium picolinate and its components in Salmonella typhimurium and L5178Y mouse lymphoma cells SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE mutagenicity; chromium; chromium picolinate; Salmonella typhimurium; mouse lymphoma ID HAMSTER OVARY CELLS; MAMMALIAN-CELLS; DAMAGE; TRIS(PICOLINATE); MECHANISMS; LOCUS; DNA AB Chromium picolinate is one of the most commonly used chromium dietary supplements available in the United States, and it has been marketed to consumers for use in weight loss, increasing muscle mass, and lowering serum cholesterol. Chromium picolinate is a synthetic compound that provides a bioavailable form of Cr(III) that is absorbed better than dietary chromium. However, there are several reports that it can have adverse effects. In order to study the mechanism of observed cellular toxicity and mutagenicity, chromium picolinate and its component compounds, chromium (III) chloride and picolinic acid, were evaluated in Salmonella typhimurium and L5178Y mouse lymphoma cells. Neither chromium picolinate nor chromium chloride induced a mutagenic response in S. typhimurium. However, in the L5178Y mouse lymphoma mutation assay, chromium picolinate induced mutagenic responses without and with the addition of S9. Published by Elsevier Ltd. C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. BioReliance, Rockville, MD USA. NCI, NIH, Bethesda, MD 20892 USA. RP Whittaker, P (reprint author), US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM paul.whittaker@cfsan.fda.gov FU NCI NIH HHS [N01-CB-87016] NR 21 TC 33 Z9 36 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-6915 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD NOV PY 2005 VL 43 IS 11 BP 1619 EP 1625 DI 10.1016/j.fct.2005.05.003 PG 7 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 971ML UT WOS:000232388300004 PM 16040181 ER PT J AU McClelland, CA Chang, YC Kwon-Chung, KJ AF McClelland, CA Chang, YC Kwon-Chung, KJ TI High frequency transformation of Cryptococcus neoformans and Cryptococcus gattii by Agrobacterium tumefaciens SO FUNGAL GENETICS AND BIOLOGY LA English DT Article DE Cryptococcus neoformans; C. gattii; Agrobacterium tumefaciens; ATMT; transformation; insertional mutagenesis ID MEDIATED-INTEGRATION REMI; T-DNA TRANSFER; INSERTIONAL MUTAGENESIS; ASPERGILLUS-FUMIGATUS; VANCOUVER-ISLAND; GENETIC-ANALYSIS; VAR.-GATTII; 2 VARIETIES; VIRULENCE; TOOL AB Cryptococcus neoformans and Cryptococcus gattii are the causative agents of cryptococcal meningoencephalitis and are amenable to genetic manipulations, making them important models of pathogenic fungi. To improve the efficiency of Agrobacterium tumefaciens mediated transformation (ATMT) in C. neoformans, we optimized various co-cultivation conditions including incubation time and temperature, and bacteria to yeast ratio. ATMT was also applied to both serotypes (B and C) of C gattii. Transformation efficiency by ATMT in C neoformans was comparable to either electroporation or biolistic transformation and gave superior efficiencies in serotypes B and C, but unlike Saccharomyces cerevisiae, adenine auxotrophy did not increase ATMT efficiency in C neoformans or C. gattii. All transformants tested were stable, with a majority containing only a single T-DNA insertion; however, homologous recombination was not observed. Additionally, we isolated adenine auxotrophs containing a single T-DNA insertion in the ADE2 gene for representative serotype B and C strains. Published by Elsevier Inc. C1 NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. RP Kwon-Chung, KJ (reprint author), NIAID, Lab Clin Infect Dis, NIH, Bldg 10,11C304, Bethesda, MD 20892 USA. EM june_kwon_chung@nih.gov FU Intramural NIH HHS NR 48 TC 40 Z9 43 U1 3 U2 10 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1087-1845 J9 FUNGAL GENET BIOL JI Fungal Genet. Biol. PD NOV PY 2005 VL 42 IS 11 BP 904 EP 913 DI 10.1016/j.fgb.2005.07.003 PG 10 WC Genetics & Heredity; Mycology SC Genetics & Heredity; Mycology GA 986BI UT WOS:000233423300003 PM 16260158 ER PT J AU Hu, N Su, H Li, WJ Giffen, C Goldstein, AM Hu, Y Wang, CY Roth, MJ Li, G Dawsey, SM Xu, Y Taylor, PR Emmert-Buck, MR AF Hu, N Su, H Li, WJ Giffen, C Goldstein, AM Hu, Y Wang, CY Roth, MJ Li, G Dawsey, SM Xu, Y Taylor, PR Emmert-Buck, MR TI Allelotyping of esophageal squamous-cell carcinoma on chromosome 13 defines deletions related to family history SO GENES CHROMOSOMES & CANCER LA English DT Article ID ALLELIC LOSS; SHANXI-PROVINCE; CANCER; GENE; CHINA; SUSCEPTIBILITY; REGIONS; IDENTIFICATION; POPULATION; MUTATIONS AB We previously reported that esophageal squamous-cell cancers (ESCC) from Shanxi Province in China show frequent allelic loss on chromosome 13. Moreover, tumors from patients with a positive family history of upper gastrointestinal tumors exhibit more frequent loss of heterozygosity (LOH) on this chromosome than do those from patients without a family history. These results suggest the possibility of a familial ESCC susceptibility gene. To investigate this phenomenon further, we performed an in-depth analysis of allelic-loss data sets from both patients with and without a family history of upper gastrointestinal tumors. Comparisons between deletion frequency and location were made with respect to family history status, risk factors, and clinical/pathologic characteristics of the tumors. The analysis confirmed that tumor LOH was significantly higher in patients with a positive family history than in those who were family-history-negative, and four common deletion regions in these family-history-positive patients were defined. Statistically significant associations were also observed between allelic loss and tumor grade and location, as well as the presence of lymph node metastases. Taken together, these data indicate that a gene or genes on chromosome 13 play an important role in the etiology and progression of ESCC. Published 2005 Wiley-Liss, Inc.(dagger) C1 NCI, Bethesda, MD 20892 USA. Natl Vaccine & Serum Inst, Beijing, Peoples R China. Shanxi Canc Hosp, Shanxi, Peoples R China. Informat Management Serv Inc, Silver Spring, MD USA. RP Taylor, PR (reprint author), NCI, Div Canc Prevent & Control, Genet Epidemiol Branch, 6116 Execut Pl,Rm 705, Bethesda, MD 20892 USA. EM ptaylor@mail.nih.gov; mb184z@nih.gov NR 32 TC 9 Z9 10 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD NOV PY 2005 VL 44 IS 3 BP 271 EP 278 DI 10.1002/gcc.20242 PG 8 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 969QA UT WOS:000232248300006 PM 16015646 ER PT J AU Badenhorst, P Xiao, H Cherbas, L Kwon, SY Voas, M Rebay, I Cherbas, P Wu, C AF Badenhorst, P Xiao, H Cherbas, L Kwon, SY Voas, M Rebay, I Cherbas, P Wu, C TI The Drosophila nucleosome remodeling factor NURF is required for Ecdysteroid signaling and metamorphosis SO GENES & DEVELOPMENT LA English DT Article DE NURF; chromatin remodeling; chromatin; Drosophila; ecdysteroid; ISWI ID GENE-EXPRESSION; ECDYSONE RECEPTOR; TRANSCRIPTIONAL ACTIVATION; GLUCOCORTICOID-RECEPTOR; NUCLEAR RECEPTORS; COMPLEX NURF; IN-VIVO; CHROMATIN; HISTONE; ISWI AB Drosophila NURF is an ISWI-containing ATP-dependent chromatin remodeling complex that regulates transcription by catalyzing nucleosome sliding. To determine in vivo gene targets of NURF, we performed whole genome expression analysis on mutants lacking the NURF-specific subunit NURF301. Strikingly, a large set of ecdysone-responsive targets is included among several hundred NURF-regulated genes. Null Nurf301 mutants do not undergo larval to pupal metamorphosis, and also enhance dominant-negative mutations in ecdysone receptor. Moreover, purified NURF binds EcR in an ecdysone-dependent manner, suggesting it is a direct effector of nuclear receptor activity. The conservation of NURF in mammals has broad implications for steroid signaling. C1 NCI, Lab Mol Cell Biol, NIH, Bethesda, MD 20814 USA. Univ Birmingham, Dept Anat, Inst Biomed Res, Birmingham B15 2TT, W Midlands, England. Indiana Univ, Dept Biol, Bloomington, IN 47405 USA. Indiana Univ, Ctr Genom & Bioinformat, Bloomington, IN 47405 USA. MIT, Whitehead Inst, Cambridge, MA 02142 USA. RP Wu, C (reprint author), NCI, Lab Mol Cell Biol, NIH, Bethesda, MD 20814 USA. EM p.w.badenhorst@bham.ac.uk; carlwu@helix.nih.gov RI Kwon, So Yeon/M-5625-2014; OI Kwon, So Yeon/0000-0002-8490-9101; Badenhorst, Paul/0000-0002-2542-0250 FU Intramural NIH HHS; Wellcome Trust NR 41 TC 89 Z9 93 U1 0 U2 7 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD NOV 1 PY 2005 VL 19 IS 21 BP 2540 EP 2545 DI 10.1101/gad.1342605 PG 6 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 981AP UT WOS:000233059700005 PM 16264191 ER PT J AU Duggal, F Klein, AP Lee, KE Klein, R Bailey-Wilson, JE Klein, BE AF Duggal, F Klein, AP Lee, KE Klein, R Bailey-Wilson, JE Klein, BE TI Identification of novel QTL for Intraocular pressure, which co-localizes with blood pressure loci SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT 14th Annual Meeting of the International-Genetic-Epidemiology-Society CY OCT 23-24, 2005 CL Park City, UT SP Int Genet Epidemiol Soc C1 NHGRI, IDRB, NIH, Baltimore, MD USA. JHMI, Dept Oncol & Pathol, Baltimore, MD USA. Univ Wisconsin, Sch Med, Dept Ophthalmol & Visual Sci, Madison, WI 53706 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD NOV PY 2005 VL 29 IS 3 MA 38 BP 245 EP 245 PG 1 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 981AK UT WOS:000233059200045 ER PT J AU Franks, PW Salbe, AD Ravussin, E Knowler, WC Hanson, RL AF Franks, PW Salbe, AD Ravussin, E Knowler, WC Hanson, RL TI Bivariate analysis of body weight and energy expenditure in young twins SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT 14th Annual Meeting of the International-Genetic-Epidemiology-Society CY OCT 23-24, 2005 CL Park City, UT SP Int Genet Epidemiol Soc C1 NIDDK, Phoenix, AZ USA. PBRC, Baton Rouge, LA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD NOV PY 2005 VL 29 IS 3 MA 53 BP 249 EP 249 PG 1 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 981AK UT WOS:000233059200060 ER PT J AU Gillanders, E Pearson, J Sorant, A Trent, J O-Connell, J Bailey-Wilson, J AF Gillanders, E Pearson, J Sorant, A Trent, J O-Connell, J Bailey-Wilson, J TI On the value of molecular haplotypes in the context of a family-based linkage study SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT 14th Annual Meeting of the International-Genetic-Epidemiology-Society CY OCT 23-24, 2005 CL Park City, UT SP Int Genet Epidemiol Soc C1 NHGRI, IDRB, NIH, Bethesda, MD USA. TGen, Phoenix, AZ USA. Univ Maryland, Baltimore, MD 21201 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD NOV PY 2005 VL 29 IS 3 MA 60 BP 251 EP 251 PG 1 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 981AK UT WOS:000233059200067 ER PT J AU Goldin, LR Landgren, O Engels, EA Pfeiffer, RM AF Goldin, LR Landgren, O Engels, EA Pfeiffer, RM TI Personal and family history of autoimmune conditions and the risk of Hodgkin lymphoma SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT 14th Annual Meeting of the International-Genetic-Epidemiology-Society CY OCT 23-24, 2005 CL Park City, UT SP Int Genet Epidemiol Soc C1 NCI, Div Canc Epidmeiol & Genet, NIH, Bethesda, MD USA. RI Pfeiffer, Ruth /F-4748-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD NOV PY 2005 VL 29 IS 3 MA 61 BP 251 EP 251 PG 1 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 981AK UT WOS:000233059200068 ER PT J AU Goldstein, AM Landi, MT Tsang, S Fraser, MC Munroe, DJ Tucker, MA AF Goldstein, AM Landi, MT Tsang, S Fraser, MC Munroe, DJ Tucker, MA TI Association of MC1R variants and risk of melanoma (MM) in MM-prone families with CDKN2A mutations SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT 14th Annual Meeting of the International-Genetic-Epidemiology-Society CY OCT 23-24, 2005 CL Park City, UT SP Int Genet Epidemiol Soc C1 NCI, DCEG, DHHS, Genet Epidemiol Br,NIH, Bethesda, MD 20892 USA. NCI, Lab Mol Technol, SAIC, DHHS,NIH, Frederick, MD USA. RI Tucker, Margaret/B-4297-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD NOV PY 2005 VL 29 IS 3 MA 62 BP 251 EP 252 PG 2 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 981AK UT WOS:000233059200069 ER PT J AU Guo, CY Lunetta, KL DeStefano, AL Cupples, LA AF Guo, CY Lunetta, KL DeStefano, AL Cupples, LA TI Combined haplotype relative risk (CHRR): A simplified genetic association test combining triads and unrelated subjects SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT 14th Annual Meeting of the International-Genetic-Epidemiology-Society CY OCT 23-24, 2005 CL Park City, UT SP Int Genet Epidemiol Soc C1 Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. NHLBI, Framingham Heart Study, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD NOV PY 2005 VL 29 IS 3 MA 68 BP 253 EP 254 PG 2 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 981AK UT WOS:000233059200075 ER PT J AU Guo, CY Cupples, LA Yang, Q AF Guo, CY Cupples, LA Yang, Q TI Testing informative missingness in family-based linkage and/or association study SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT 14th Annual Meeting of the International-Genetic-Epidemiology-Society CY OCT 23-24, 2005 CL Park City, UT SP Int Genet Epidemiol Soc C1 Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. Boston Univ, Dept Biostat, Boston, MA 02215 USA. NHLBI, Framingham Heart Study, Bethesda, MD 20892 USA. RI Yang, Qiong/G-5438-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD NOV PY 2005 VL 29 IS 3 MA 69 BP 254 EP 254 PG 1 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 981AK UT WOS:000233059200076 ER PT J AU Kraft, P Hunter, D Chanock, S Hoover, R Gerhard, D Thomas, G AF Kraft, P Hunter, D Chanock, S Hoover, R Gerhard, D Thomas, G TI Genome-wide association scans for prostate and breast cancer: design and analysis SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT 14th Annual Meeting of the International-Genetic-Epidemiology-Society CY OCT 23-24, 2005 CL Park City, UT SP Int Genet Epidemiol Soc C1 Harvard Univ, SPH, Prog Mol & Genet Epi, Cambridge, MA 02138 USA. NCI, Bethesda, MD 20892 USA. NCI, Div Canc Epi & Genet, Bethesda, MD 20892 USA. NCI, Off Canc Genom, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD NOV PY 2005 VL 29 IS 3 MA 86 BP 259 EP 259 PG 1 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 981AK UT WOS:000233059200093 ER PT J AU Lin, JP O'Donnell, CJ Cupples, LA AF Lin, JP O'Donnell, CJ Cupples, LA TI A genome-wide scan for quantitative trait loci of serum gamma glutamyltransferase - the Framingham Offspring Study SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT 14th Annual Meeting of the International-Genetic-Epidemiology-Society CY OCT 23-24, 2005 CL Park City, UT SP Int Genet Epidemiol Soc C1 NHLBI, Off Biostat, DECA, Bethesda, MD 20892 USA. NHLBI, Framingham Heart Study, DECA, Bethesda, MD 20892 USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD NOV PY 2005 VL 29 IS 3 MA 103 BP 264 EP 264 PG 1 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 981AK UT WOS:000233059200110 ER PT J AU Nicodemus, KK Egan, MF Meyers, J Rujescu, D Weinberger, DR AF Nicodemus, KK Egan, MF Meyers, J Rujescu, D Weinberger, DR TI Assessing sensitivity and percent agreement of posterior subpopulation assignment across clustering methods using both a multiethnic and Caucasian-based sample SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT 14th Annual Meeting of the International-Genetic-Epidemiology-Society CY OCT 23-24, 2005 CL Park City, UT SP Int Genet Epidemiol Soc C1 NIMH, Genes Cognit & Psychosis Program, CBDB, NIH, Bethesda, MD 20892 USA. Univ Munich, Dept Psychiat, D-8000 Munich, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD NOV PY 2005 VL 29 IS 3 MA 126 BP 271 EP 271 PG 1 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 981AK UT WOS:000233059200133 ER PT J AU Turley-Stoulig, TN Sorant, AJM Bailey-Wilson, JE Mandal, DM AF Turley-Stoulig, TN Sorant, AJM Bailey-Wilson, JE Mandal, DM TI Use of covariates in linkage analysis: Comparison of model-based and model-free methods SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT 14th Annual Meeting of the International-Genetic-Epidemiology-Society CY OCT 23-24, 2005 CL Park City, UT SP Int Genet Epidemiol Soc C1 SE Louisiana Univ, Hammond, LA 70402 USA. NHGRI, NIH, Baltimore, MD USA. Louisiana State Univ, Hlth Sci Ctr, New Orleans, LA 70112 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD NOV PY 2005 VL 29 IS 3 MA 161 BP 281 EP 281 PG 1 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 981AK UT WOS:000233059200168 ER PT J AU Wilk, JB Manning, AK Dupuis, J Cupples, LA Larson, MG Newton-Cheh, C Demissie, S DeStefano, AL Hwang, SJ Liu, C Yang, Q Lunetta, KL AF Wilk, JB Manning, AK Dupuis, J Cupples, LA Larson, MG Newton-Cheh, C Demissie, S DeStefano, AL Hwang, SJ Liu, C Yang, Q Lunetta, KL TI No evidence of major population substructure in the Framingham Heart Study SO GENETIC EPIDEMIOLOGY LA English DT Meeting Abstract CT 14th Annual Meeting of the International-Genetic-Epidemiology-Society CY OCT 23-24, 2005 CL Park City, UT SP Int Genet Epidemiol Soc C1 Boston Univ, Sch Med & Publ Hlth, NHLBI, Framingham Heart Study, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Yang, Qiong/G-5438-2014 NR 0 TC 4 Z9 4 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0741-0395 J9 GENET EPIDEMIOL JI Genet. Epidemiol. PD NOV PY 2005 VL 29 IS 3 MA 177 BP 286 EP 286 PG 1 WC Genetics & Heredity; Mathematical & Computational Biology SC Genetics & Heredity; Mathematical & Computational Biology GA 981AK UT WOS:000233059200184 ER PT J AU Kouprina, N Pavlicek, A Noskov, VN Solomon, G Otstot, J Isaacs, W Carpten, JD Trent, JM Schleutker, J Barrett, JC Jurka, J Larionov, V AF Kouprina, N Pavlicek, A Noskov, VN Solomon, G Otstot, J Isaacs, W Carpten, JD Trent, JM Schleutker, J Barrett, JC Jurka, J Larionov, V TI Dynamic structure of the SPANX gene cluster mapped to the prostate cancer susceptibility locus HPCX at Xq27 SO GENOME RESEARCH LA English DT Article ID DOUBLE-STRAND BREAK; GENOME-WIDE SCAN; X-CHROMOSOME; CELL-LINES; RECOMBINATION CLONING; REPETITIVE ELEMENTS; HUMAN SPERMATOZOA; LINKAGE ANALYSIS; COMPLEX GENOMES; EXPRESSION AB Genetic linkage studies indicate that germline variations in a gene or genes on chromosome Xq27-28 are implicated in prostate carcinogenesis. The linkage peak of prostate cancer overlies a region of -750 kb containin-five SPANX genes (SPANX-A1, -A2, -B, -C, and -D) encoding sperm proteins associated with the nucleus; their expression was also detected in a variety of cancers. SPANX genes are > 95% identical and reside within large segmental duplications (SDs) with a high level of similarity, which confounds mutational analysis of this gene family by routine PCR methods. In this work, we applied transformation-associated recombination cloning (TAR) in yeast to characterize individual SPANX genes from prostate cancer patients showing linkage to Xq27-28 and unaffected controls. Analysis of genomic TAR clones revealed a dynamic nature of the replicated region of linkage. Both frequent gene deletion/duplication and homology-based sequence transfer events were identified within the region and were presumably caused by recombinational interactions between SDs harboring the SPANX genes. These interactions contribute to diversity of the SPANX coding regions in humans. We speculate that the predisposition to prostate cancer in X-linked families is an example of a genomic disease caused by a specific architecture of the SPANX gene cluster. C1 NCI, Lab Biosyst & Canc, Bethesda, MD 20892 USA. Genet Informat Res Inst, Mountain View, CA 94043 USA. NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. Johns Hopkins Univ, Dept Urol, Baltimore, MD 21287 USA. Translat Genom Res Inst, Phoenix, TX 85004 USA. Univ Tampere, Inst Med Technol, Canc Genet Lab, FIN-33014 Tampere, Finland. RP Larionov, V (reprint author), NCI, Lab Biosyst & Canc, Bethesda, MD 20892 USA. EM larionov@mail.nih.gov FU Intramural NIH HHS NR 51 TC 30 Z9 39 U1 0 U2 0 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 NOV PY 2005 VL 15 IS 11 BP 1477 EP 1486 DI 10.1101/gr.4212705 PG 10 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 978QZ UT WOS:000232889400003 PM 16251457 ER PT J AU Zaitlen, NA Kang, HM Feolo, ML Sherry, ST Halperin, E Eskin, E AF Zaitlen, NA Kang, HM Feolo, ML Sherry, ST Halperin, E Eskin, E TI Inference and analysis of haplotypes from combined genotyping studies deposited in dbSNP SO GENOME RESEARCH LA English DT Article ID SINGLE-NUCLEOTIDE POLYMORPHISMS; CANDIDATE GENES; HUMAN GENOME; SEQUENCE VARIATION; RECONSTRUCTION; POPULATIONS; DIVERSITY; PATTERNS; BLOCKS AB In the attempt to understand human variation and the genetic basis of complex disease, a tremendous number of single nucleotide polymorphisms (SNPs) have been discovered and deposited into NCBI's dbSNP public database. More than 2.7 million SNPs in the database have genotype information. This data provides an invaluable resource for understanding the structure of human variation and the design of genetic association Studies. The genotypes deposited to dbSNP are unphased, and thus, the haplotype information is unknown. We applied the phasing method HAP to obtain the haplotype information, block partitions, and tag SNPs for all publicly available genotype data and deposited this information into the dbSNP database. We also deposited the orthologous chimpanzee reference sequence for each predicted haplotype block computed using the UCSC BLASTZ alignments of human and chimpanzee. Using dbSNP, researchers can now easily perform analyses using multiple genotype data sets from the same genomic regions. Dense and sparse genotype data sets from the same region were combined to show that the number of common haplotypes is significantly underestimated in whole genome data sets, while the predicted haplotypes over the common SNPs are consistent between Studies. To validate the accuracy of the predictions, we benchmarked HAP's running time and phasing accuracy against PHASE. Although HAP is slightly less accurate than PHASE, HAP is over 1000 times faster than PHASE, making it Suitable for application to the entire set of genotypes in dbSNP. C1 Univ Calif San Diego, Bioinformat Program, La Jolla, CA 92093 USA. Univ Calif San Diego, Dept Comp Sci, La Jolla, CA 92093 USA. NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. Int Comp Sci Inst, Berkeley, CA 94704 USA. RP Eskin, E (reprint author), Univ Calif San Diego, Bioinformat Program, La Jolla, CA 92093 USA. EM eeskin@cs.ucsd.edu RI Eskin, Eleazar/J-9187-2012 OI Eskin, Eleazar/0000-0003-1149-4758 FU Intramural NIH HHS; NCRR NIH HHS [P41 RR008605, P41 RR08605] NR 22 TC 12 Z9 13 U1 0 U2 0 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 NOV PY 2005 VL 15 IS 11 BP 1594 EP 1600 DI 10.1101/gr.4297805 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 978QZ UT WOS:000232889400016 PM 16251470 ER PT J AU Lin, W Yang, HH Lee, MP AF Lin, W Yang, HH Lee, MP TI Allelic variation in gene expression identified through computational analysis of the dbEST database SO GENOMICS LA English DT Article DE allelic variation; gene expression; statistics; imprinting; EST ID MESSENGER-RNA STABILITY; TRANSCRIPTIONAL REGULATION; REGULATORY VARIATION; GENOME; CLUSTER; SEQUENCES; CANCER; MOUSE AB Differential expression between the two alleles of an individual and between people with different genotypes has been commonly observed. Quantitative differences in gene expression between people may provide the genetic basis for the phenotypic difference between individuals and may be the primary cause of complex diseases. In this paper, we developed a computational method to identify genes that displayed allelic variation in gene expression in human EST libraries. To model allele-specific gene expression, we first identified EST libraries in which both A and B alleles were expressed and then identified allelic variation in gene expression based on the EST counts for each allele using a binomial test. Among 1107 SNPs that had a sufficient number of ESTs for the analysis, 524 (47%) displayed allelic variation in at least one cDNA library. We verified experimentally the allelic variation in gene expression for 6 of these SNPs. The frequency of allelic variation observed in EST libraries was similar to the previous studies using the SNP chip and primer extension method. We found that genes that displayed allelic variation were distributed throughout the human genome and were enriched in certain chromosome regions. The SNPs and genes identified in this study will provide a rich source for evaluating the effects of those SNPs and associated haplotypes in human health and diseases. Published by Elsevier Inc. C1 NCI, Lab Populat Genet, Bethesda, MD 20892 USA. RP Lee, MP (reprint author), NCI, Lab Populat Genet, Bethesda, MD 20892 USA. EM leemax@mail.nih.gov NR 31 TC 11 Z9 12 U1 1 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0888-7543 J9 GENOMICS JI Genomics PD NOV PY 2005 VL 86 IS 5 BP 518 EP 527 DI 10.1016/j.ygeno.2005.05.004 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 978JR UT WOS:000232869900002 PM 15993562 ER PT J AU Cho, YS Griswold, A Campbell, C Min, KT AF Cho, YS Griswold, A Campbell, C Min, KT TI Individual histone deacetylases in Drosophila modulate transcription of distinct genes SO GENOMICS LA English DT Article DE drosophila; HDACs; microarray; aging; HDAC inhibitors ID LIFE-SPAN; MUSCLE DIFFERENTIATION; CAENORHABDITIS-ELEGANS; HUNTINGTONS-DISEASE; MICROARRAY ANALYSIS; YEAST; SIR2; INHIBITORS; GENOME; SEGMENTATION AB Lysine residues on the N-terminal tails of histories in chromatin are the primary targets of histone acetyltransferases (HATs) and histone deacetylases (HDACs) in eukaryotes. Regulation of historic acetylation by these two classes of enzymes plays significant roles in controlling transcriptional activity in cells. Eukaryotic organisms have several different HDACs, but the biological roles of each HDAC are still not clear. To understand the physiological functions of HDACs, we characterized six different Drosophila HDACs, including Rpd3, HDAC3, HDAC4, HDAC6-S, HDAC6-L, and Sir2, by developmental expression pattern, transcriptional profiles of target genes, and sensitivity to HDAC inhibitors. We found that each HDAC has a distinct temporal expression pattern and regulates transcription of a unique set of genes. Furthermore, we demonstrated differential sensitivity of HDACs to inhibitors. These results show that each individual HDAC plays different roles in regulating genes involved in various biological processes. Published by Elsevier Inc. C1 NINDS, Neurogenet Branch, NIH, Bethesda, MD 20892 USA. RP Min, KT (reprint author), NINDS, Neurogenet Branch, NIH, MSC 3705,Bldg 35,Room 2A-002, Bethesda, MD 20892 USA. EM mink@ninds.nih.gov RI Griswold, Anthony/B-7507-2012; OI min, kyung-tai/0000-0003-0983-4258 FU Intramural NIH HHS NR 62 TC 43 Z9 50 U1 2 U2 10 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 NOV PY 2005 VL 86 IS 5 BP 606 EP 617 DI 10.1016/j.ygeno.2005.07.007 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 978JR UT WOS:000232869900009 PM 16137856 ER PT J AU Sparks, SE Ciccone, C Lalor, M Orvisky, E Klootwijk, R Savelkoul, PJ Dalakas, MC Krasnewich, DM Gahl, WA Huizing, M AF Sparks, SE Ciccone, C Lalor, M Orvisky, E Klootwijk, R Savelkoul, PJ Dalakas, MC Krasnewich, DM Gahl, WA Huizing, M TI Use of a cell-free system to determine UDP-N-acetylglucosamine 2-epimerase and N-acetylmannosamine kinase activities in human hereditary inclusion body myopathy SO GLYCOBIOLOGY LA English DT Article DE cell-free transcription-translation; GNE; HIBM; MNK enzymes; sialic acid ID D-GLUCOSAMINE 2-EPIMERASE; RENIN-BINDING PROTEIN; ACID STORAGE DISEASE; 2-EPIMERASE/N-ACETYLMANNOSAMINE KINASE; RIMMED VACUOLES; DISTAL MYOPATHY; GNE GENE; UDP-N-ACETYLGLUCOSAMINE-2-EPIMERASE/N-ACETYLMANNOSAMINE KINASE; BIFUNCTIONAL ENZYME; GLCNAC 2-EPIMERASE AB Hereditary inclusion body myopathy (HIBM) is an autosomal recessive neuromuscular disorder associated with mutations in uridine diphosphate (UDP)-N-acetylglucosamine (GlcNAc) 2-epimerase (GNE)/N-acetylmannosamine (ManNAc) kinase (MNK), the bifunctional and rate-limiting enzyme of sialic acid biosynthesis. We developed individual GNE and MNK enzymatic assays and determined reduced activities in cultured fibroblasts of patients, with HIBM harboring missense mutations in either or both the GNE and MNK enzymatic domains. To assess the effects of individual mutations on enzyme activity, normal and mutated GNE/MNK enzymatic domains were synthesized in a cell-free in vitro transcription-translation system and subjected to the GNE and MNK enzymatic assays. This cell-free system was validated for both GNE and MNK activities, and it revealed that mutations in one enzymatic domain (in GNE, G135V, V216A, and R246W; in MNK, A631V, M712T) affected not only that domain's enzyme activity, but also the activity of the other domain. Moreover, studies of the residual enzyme activity associated with specific mutations revealed a discrepancy between the fibroblasts and the cell-free systems. Fibroblasts exhibited higher residual activities of both GNE and MNK than the cell-free system. These findings add complexity to the tightly regulated system of sialic acid biosynthesis. This cell-free approach can be applied to other glycosylation pathway enzymes that are difficult to evaluate in whole cells because their substrate specificities overlap with those of ancillary enzymes. C1 NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Med Ctr, Dept Oncol, Lombardi Comprehens Canc Ctr, Washington, DC 20007 USA. NINDS, Neuromuscular Dis Sect, NIH, Bethesda, MD 20892 USA. NIH, Intramural Program, Bethesda, MD 20892 USA. RP Huizing, M (reprint author), NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. EM mhuizing@mail.nih.gov NR 46 TC 29 Z9 29 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2005 VL 15 IS 11 BP 1102 EP 1110 DI 10.1093/glycob/cwi100 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 979CP UT WOS:000232920300007 PM 15987957 ER PT J AU Proia, RL AF Proia, RL TI Glycosphingolipids in nervous system development, stability, and disease SO GLYCOBIOLOGY LA English DT Meeting Abstract CT Meeting of the Society-for-Glycobiology CY NOV 09-12, 2005 CL Boston, MA SP Soc Glycobiol C1 NIDDK, NIH, Bethesda, MD 20892 USA. RI Proia, Richard/A-7908-2012 NR 0 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 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2005 VL 15 IS 11 MA 22 BP 1192 EP 1192 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 979CP UT WOS:000232920300035 ER PT J AU Sacks, D Kamhawi, S Ramalho-Ortigao, M Lawyer, P Valenzuela, J AF Sacks, D Kamhawi, S Ramalho-Ortigao, M Lawyer, P Valenzuela, J TI Lipophosphoglycan-galectin interactions controlling sand fly vector competence for Leishmania major SO GLYCOBIOLOGY LA English DT Meeting Abstract CT Meeting of the Society-for-Glycobiology CY NOV 09-12, 2005 CL Boston, MA SP Soc Glycobiol C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. RI Ramalho-Ortigao, Marcelo/E-8225-2011 NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2005 VL 15 IS 11 MA 28 BP 1193 EP 1193 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 979CP UT WOS:000232920300041 ER PT J AU Ramasamy, V Ramakrishnan, B Boeggeman, E Ratner, DM Seeberger, PH Qasba, PK AF Ramasamy, V Ramakrishnan, B Boeggeman, E Ratner, DM Seeberger, PH Qasba, PK TI Oligosaccharide preferences of beta 1,4-galactosyltransferase-I: Crystal structures of Met340His mutant of human beta 1,4-galactosyltransferase-I with a pentasaccharide and trisaccharides of the N-glycan moiety SO GLYCOBIOLOGY LA English DT Meeting Abstract CT Meeting of the Society-for-Glycobiology CY NOV 09-12, 2005 CL Boston, MA SP Soc Glycobiol C1 NCI, Struct Glycobiol Sect, CCR Nanobiol Program, NIH, Frederick, MD 21702 USA. NCI, Basic Res Program, SAIC Frederick Inc, CCR Nanobiol Program,NIH, Frederick, MD 21702 USA. MIT, Dept Chem, Cambridge, MA 02139 USA. ETH Honggerberg, Organ Chem Lab, CH-8093 Zurich, Switzerland. NR 0 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 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2005 VL 15 IS 11 MA 64 BP 1202 EP 1203 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 979CP UT WOS:000232920300077 ER PT J AU Tian, E Ten Hagen, KG AF Tian, E Ten Hagen, KG TI Expression of the UDP-GalNAc: Polypeptide N-acetylgalactosaminyltransferase family is spatially and temporally regulated during Drosophila development SO GLYCOBIOLOGY LA English DT Meeting Abstract CT Meeting of the Society-for-Glycobiology CY NOV 09-12, 2005 CL Boston, MA SP Soc Glycobiol C1 NIDCR, Dev Glycobiol Unit, NIH, Bethesda, MD 20892 USA. NR 0 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 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2005 VL 15 IS 11 MA 130 BP 1218 EP 1218 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 979CP UT WOS:000232920300143 ER PT J AU Zhou, DP Mattner, J Cantu, C Schrantz, N Yin, N Gao, Y Sagiv, Y Hudspeth, K Wu, YP Yamashita, T Teneberg, S Wang, DC Proia, RL Levery, SB Savage, P Teyton, L Bendelac, A AF Zhou, DP Mattner, J Cantu, C Schrantz, N Yin, N Gao, Y Sagiv, Y Hudspeth, K Wu, YP Yamashita, T Teneberg, S Wang, DC Proia, RL Levery, SB Savage, P Teyton, L Bendelac, A TI Metabolic pathways of natural glycolipid ligands for NKT cells in tumor immunity SO GLYCOBIOLOGY LA English DT Meeting Abstract CT Meeting of the Society-for-Glycobiology CY NOV 09-12, 2005 CL Boston, MA SP Soc Glycobiol C1 Univ Chicago, Dept Pathol, Chicago, IL 60637 USA. Howard Hughes Med Inst, Chicago, IL 60637 USA. Scripps Res Inst, La Jolla, CA 92037 USA. Brigham Young Univ, Dept Chem & Biochem, Provo, UT 84602 USA. NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. Univ Gothenburg, Inst Med Biochem, SE-40530 Gothenburg, Sweden. Chinese Acad Sci, Inst Biophys, Beijing 100101, Peoples R China. Univ New Hampshire, Dept Chem, Durham, NH 03824 USA. RI Proia, Richard/A-7908-2012; Zhou, Dapeng/D-3059-2014 OI Zhou, Dapeng/0000-0003-1347-3811 NR 0 TC 1 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2005 VL 15 IS 11 MA 184 BP 1232 EP 1233 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 979CP UT WOS:000232920300197 ER PT J AU Tenno, M Ohtsubo, K Hagen, FK Tabak, LA Marth, JD AF Tenno, M Ohtsubo, K Hagen, FK Tabak, LA Marth, JD TI Threshold contribution to selectin ligand formation by polypeptide GalNAcT-1 directs tissue-specific lymphocyte retention in sustaining humoral immunity SO GLYCOBIOLOGY LA English DT Meeting Abstract CT Meeting of the Society-for-Glycobiology CY NOV 09-12, 2005 CL Boston, MA SP Soc Glycobiol C1 Univ Calif San Diego, Howard Hughes Med Inst, La Jolla, CA 92093 USA. Univ Calif San Diego, Dept Cellular & Mol Biol, La Jolla, CA 92093 USA. Univ Rochester, Sch Med & Dent, Dept Biochem & Biophys, Rochester, NY 14642 USA. NIDDKD, Biol Chem Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2005 VL 15 IS 11 MA 209 BP 1238 EP 1239 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 979CP UT WOS:000232920300222 ER PT J AU Forsythe, ME Hennessey, PT Brodigan, TM Love, DC Ashwell, G Krause, M Hanover, JA AF Forsythe, ME Hennessey, PT Brodigan, TM Love, DC Ashwell, G Krause, M Hanover, JA TI A Caenorhabditis elegans model of insulin resistance: An OGT-1 knockout shows altered macronutrient storage and dauer formation SO GLYCOBIOLOGY LA English DT Meeting Abstract CT Meeting of the Society-for-Glycobiology CY NOV 09-12, 2005 CL Boston, MA SP Soc Glycobiol C1 NIDDKD, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA. NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NR 0 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 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2005 VL 15 IS 11 MA 235 BP 1245 EP 1245 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 979CP UT WOS:000232920300248 ER PT J AU Savelkoul, PJ Sparks, S Rakocevic, G Klootwijk, R Ciccone, C Dalakas, M Krasnewich, D Gahl, W Huizing, M AF Savelkoul, PJ Sparks, S Rakocevic, G Klootwijk, R Ciccone, C Dalakas, M Krasnewich, D Gahl, W Huizing, M TI Evaluation of the glycosylation status of alpha-dystroglycan in hereditary inclusion body myopathy SO GLYCOBIOLOGY LA English DT Meeting Abstract CT Meeting of the Society-for-Glycobiology CY NOV 09-12, 2005 CL Boston, MA SP Soc Glycobiol C1 NHGRI, Sect Human Biochem Genet, Med Genet Branch, NIH, Bethesda, MD 20892 USA. NINDS, Neuromus Dis Sect, NIH, Bethesda, MD 20892 USA. NR 0 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 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2005 VL 15 IS 11 MA 239 BP 1246 EP 1247 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 979CP UT WOS:000232920300252 ER PT J AU Klootwijk, R Savelkoul, PJ Ciccone, C Krasnewich, DM Gahl, WA Huizing, M AF Klootwijk, R Savelkoul, PJ Ciccone, C Krasnewich, DM Gahl, WA Huizing, M TI Design of a quantitative method for detection of allele-specific RNA expression SO GLYCOBIOLOGY LA English DT Meeting Abstract CT Meeting of the Society-for-Glycobiology CY NOV 09-12, 2005 CL Boston, MA SP Soc Glycobiol C1 NHGRI, MGB, NIH, Bethesda, MD 20892 USA. NR 0 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 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2005 VL 15 IS 11 MA 246 BP 1248 EP 1248 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 979CP UT WOS:000232920300259 ER PT J AU Watanabe, T Kitani, A Strober, W AF Watanabe, T Kitani, A Strober, W TI Crohn's disease - NOD2 regulation of Toll-like receptor responses and the pathogenesis of Crohn's disease SO GUT LA English DT Editorial Material ID BACTERIAL MURAMYL DIPEPTIDE; HUMAN MONOCYTIC CELLS; EXPERIMENTAL COLITIS; PANETH CELLS; DIAMINOPIMELIC ACID; HOST RECOGNITION; CARD15 MUTATIONS; TRANSGENIC MICE; SMALL-INTESTINE; DEFENSIN AB NOD2 signalling can both positively and negatively regulate Toll-like receptor (TLR) responses. Previous studies have shown that lack of NOD2 signalling ( in NOD2 knockout mice) leads to increased peptidoglycan induction of interleukin (IL)-12 via TLR2. Studies in this issue of Gut show that lack of NOD2 signalling ( in patients with NOD2 mutations) leads to decreased CpG induction of tumour necrosis factor and IL-8 via TLR9. The first type of abnormality suggests that NOD2 mutations act by enhancing effector T cell function and the second that NOD2 mutations act by impairing regulatory T cell function. We weigh these possibilities. C1 NIAID, Mucosal Immun Sect, Host Def Lab, NIH, Bethesda, MD 20892 USA. RP Strober, W (reprint author), NIAID, Mucosal Immun Sect, Host Def Lab, NIH, Bldg 10 CRC,Room 5W3940,10 Ctr Dr, Bethesda, MD 20892 USA. EM wstrober@niaid.nih.gov NR 43 TC 44 Z9 47 U1 0 U2 5 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 J9 GUT JI Gut PD NOV PY 2005 VL 54 IS 11 BP 1515 EP 1518 DI 10.1136/gut.2005.071795 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 974HJ UT WOS:000232581800003 PM 16227353 ER PT J AU Fuchs, VR Emanuel, EJ AF Fuchs, VR Emanuel, EJ TI Health care reform: Why? What? When? SO HEALTH AFFAIRS LA English DT Article ID SHATTUCK LECTURE; INSURANCE; COVERAGE; PROPOSAL; QUALITY AB Dissatisfaction with the U.S. health care system is widespread, but no consensus has emerged as to how to reform it. The principal methods of finance-employer-based insurance, means-tested insurance, and Medicare-are deeply and irreparably flawed. Policymakers confront two fundamental questions: Should reform be incremental or comprehensive? And should priority be given to reforming the financing system or to improving organization and delivery? We consider here several proposals for incremental reform and three for comprehensive reform: individual mandates with subsidies, single payer, and universal vouchers. Over the long term, reform is likely to come in response to a major war, depression, or large-scale civil unrest. C1 Stanford Univ, Stanford, CA 94305 USA. NIH, Warren G Magnuson Clin Ctr, Dept Clin Bioeth, Bethesda, MD 20892 USA. RP Fuchs, VR (reprint author), Stanford Univ, Stanford, CA 94305 USA. EM fuchs@newage3.stanford.edu NR 45 TC 23 Z9 23 U1 1 U2 4 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD NOV-DEC PY 2005 VL 24 IS 6 BP 1399 EP 1414 DI 10.1377/hlthaff.24.6.1399 PG 16 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 008IM UT WOS:000235033500003 PM 16284011 ER PT J AU Zuvekas, SH Rupp, AE Norquist, GS AF Zuvekas, SH Rupp, AE Norquist, GS TI Update: Special report - The impacts of mental health parity and managed care in one large employer group: A reexamination SO HEALTH AFFAIRS LA English DT Editorial Material ID LONGITUDINAL DATA-ANALYSIS; NATIONAL TRENDS; MODELS AB Although the impacts of carve-outs to managed behavioral health care organizations (MBHOs) and parity mandates on costs are largely settled in the literature, their impacts on access are less clear. Here we reexamine a study published by Samuel Zuvekas and colleagues in this journal, which found that the number of people receiving mental health/substance abuse treatment increased by almost 50 percent after the introduction of mental health parity and an MBHO. Using multivariate panel data methods, we now suggest that secular trends were largely responsible for this increase. C1 AHRQ, Ctr Financing Access & Cost Trends, Rockville, MD USA. NIMH, Mental Hlth Econ Res Program, Bethesda, MD 20892 USA. Univ Mississippi, Med Ctr, Dept Psychiat & Human Behav, Jackson, MS 39216 USA. RP Zuvekas, SH (reprint author), AHRQ, Ctr Financing Access & Cost Trends, Rockville, MD USA. EM szuvekas@ahrq.gov NR 10 TC 7 Z9 7 U1 0 U2 1 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD NOV-DEC PY 2005 VL 24 IS 6 BP 1668 EP 1671 DI 10.1377/hlthaff.24.6.1668 PG 4 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 008IM UT WOS:000235033500033 PM 16284042 ER PT J AU Hampson, LA Emanuel, EJ AF Hampson, LA Emanuel, EJ TI End-of-life care: The authors respond SO HEALTH AFFAIRS LA English DT Letter C1 Univ Michigan, Sch Med, Ann Arbor, MI 48109 USA. NIH, Bethesda, MD 20892 USA. RP Hampson, LA (reprint author), Univ Michigan, Sch Med, Ann Arbor, MI 48109 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD NOV-DEC PY 2005 VL 24 IS 6 BP 1687 EP 1688 DI 10.1377/hlthaff.24.6.1687 PG 2 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 008IM UT WOS:000235033500045 PM 16284050 ER PT J AU Suzman, R Haaga, J AF Suzman, R Haaga, J TI Foreword SO HEALTH AFFAIRS LA English DT Editorial Material C1 NIA, Bethesda, MD 20892 USA. RP Suzman, R (reprint author), NIA, Bethesda, MD 20892 USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD NOV-DEC PY 2005 VL 24 IS 6 BP W5R1 EP W5R3 DI 10.1377/hlthaff.W5.R1 PG 3 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 008IM UT WOS:000235033500051 ER PT J AU Tiro, JA Diamond, PM Perz, CA Fernandez, M Rakowski, W DiClemente, CC Vernon, SW AF Tiro, JA Diamond, PM Perz, CA Fernandez, M Rakowski, W DiClemente, CC Vernon, SW TI Validation of scales measuring attitudes and norms related to mammography screening in women veterans SO HEALTH PSYCHOLOGY LA English DT Article DE mammography; attitudes; subjective norms; construct validation ID HEALTH BELIEF MODEL; BREAST-CANCER; TRANSTHEORETICAL MODEL; DECISIONAL BALANCE; FAMILY-HISTORY; PSYCHOLOGICAL DISTRESS; BEHAVIOR-CHANGE; BARRIERS SCALE; OVARIAN-CANCER; RISK AB Validation of psychosocial measures for use in mammography screening research has been given inadequate attention in the literature. The authors report on the validation of 5 measures examining 4 attitudinal constructs (i.e., pros, cons, outcome expectations, and cancer worries) and I social influence construct (i.e., subjective norms) in a 22-item inventory. The study participants consisted of a national, randomly sampled population of women veterans (n = 2,910). After minor revision of scales, the authors found independent measures for 4 constructs: pros, cons, cancer worries, and subjective norms. The authors concluded that these scales have acceptable psychometric properties; support construct validity; and provide brief, reliable, and valid measures of attitudes toward and norms regarding mammography screening. These scales may be useful for intervention research. C1 Univ Texas, Sch Publ Hlth, Ctr Hlth Promot & Prevent Res, Houston, TX USA. Univ Houston, Dept Psychol, Houston, TX 77004 USA. Brown Univ, Ctr Gerontol & Hlth Care Res, Providence, RI 02912 USA. Univ Maryland Baltimore Cty, Dept Psychol, Baltimore, MD 21228 USA. RP Tiro, JA (reprint author), NCI, Div Canc Control & Populat Sci, 6130 Execut Blvd,EPN 4103A,MSC 7331, Bethesda, MD 20892 USA. EM tiroj@mail.nih.gov OI Tiro, Jasmin/0000-0001-8300-0441 FU NCI NIH HHS [R01 CA76330] NR 79 TC 13 Z9 13 U1 1 U2 5 PU AMER PSYCHOLOGICAL ASSOC/EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0278-6133 J9 HEALTH PSYCHOL JI Health Psychol. PD NOV PY 2005 VL 24 IS 6 BP 555 EP 566 DI 10.1037/0278-6133.24.6.555 PG 12 WC Psychology, Clinical; Psychology SC Psychology GA 986ML UT WOS:000233453600003 PM 16287401 ER PT J AU Schofield, DJ Bartosch, B Shimizu, YK Allander, T Alter, HJ Emerson, SU Cosset, FL Purcell, RH AF Schofield, DJ Bartosch, B Shimizu, YK Allander, T Alter, HJ Emerson, SU Cosset, FL Purcell, RH TI Human monoclonal antibodies that react with the E2 glycoprotein of hepatitis C virus and possess neutralizing activity SO HEPATOLOGY LA English DT Article ID ENVELOPE GLYCOPROTEIN; REPERTOIRE CLONING; PHAGE DISPLAY; CONFORMATIONAL EPITOPES; GAMMA-GLOBULIN; CELL ENTRY; NON-A; BINDING; CD81; PROTEIN AB Active and/or passive immunoprophylaxis against hepatitis C virus (HCV) remain unachieved goals. Monoclonal antibodies might provide one approach to protection. We derived human monoclonal antibodies from the bone marrow of a patient with a well-controlled HCV infection of 22 years duration. Five distinct antibodies reactive with the E2 glycoprotein of the homologous I a strain of HCV were recovered as antigen-binding fragments (FAbs). They demonstrated affinity constants as high as 2 nanomolar. "Neutralization of binding" titers paralleled the affinity constants. All five FAbs reacted with soluble E2 protein only in nonreducing gels, indicating that the relevant epitopes were conformational. The FAbs could be divided into two groups, based on competition analysis. Three of the FAbs neutralized the infectivity of pseudotyped virus particles (pp) bearing the envelope glycoproteins of the homologous HCV strain (genotype 1 a). The three FAbs also neutralized genotype 1b pp and one also neutralized genotype 2a pp. In conclusion, one or more of these monoclonal antibodies may be useful in preventing infections by HCV belonging to genotype I or 2, the most medically important genotypes worldwide. C1 NIAID, Hepatitis Viruses Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. NIAID, Mol Hepatitis Sect, Infect Dis Lab, Bethesda, MD 20892 USA. NIH, Warren G Magnuson Clin Ctr, Dept Transfus Med, Bethesda, MD 20892 USA. INSERM 4412, Lab Vectorol Retrovirale & Therapie Gen, IFR 128, Ecole Normale Super Lyon, F-69008 Lyon, France. Int Med Ctr Japan, Inst Res, Dept Resp Dis, Tokyo, Japan. RP Purcell, RH (reprint author), NIAID, Hepatitis Viruses Sect, Infect Dis Lab, NIH, Bldg 50 Rm 6523,50 S Dr MSC-8009, Bethesda, MD 20892 USA. EM rpurcell@niaid.nih.gov NR 44 TC 48 Z9 50 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD NOV PY 2005 VL 42 IS 5 BP 1055 EP 1062 DI 10.1002/hep.20906 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 979NE UT WOS:000232948100010 PM 16250048 ER PT J AU Mohlke, KL Jackson, AU Scott, LJ Peck, EC Suh, YD Chines, PS Watanabe, RM Buchanan, TA Conneely, KN Erdos, MR Narisu, N Enloe, S Valle, TT Tuomilehto, J Bergman, RN Boehnke, M Collins, FS AF Mohlke, KL Jackson, AU Scott, LJ Peck, EC Suh, YD Chines, PS Watanabe, RM Buchanan, TA Conneely, KN Erdos, MR Narisu, N Enloe, S Valle, TT Tuomilehto, J Bergman, RN Boehnke, M Collins, FS TI Mitochondrial polymorphisms and susceptibility to type 2 diabetes-related traits in Finns SO HUMAN GENETICS LA English DT Article ID MAJOR NONCODING REGION; INSULIN-RESISTANCE; SKELETAL-MUSCLE; GENETICS FUSION; MAPPING GENES; DNA MUTATION; D-LOOP; MELLITUS; VARIANT; FINLAND AB Mitochondria play an integral role in ATP production in cells and are involved in glucose metabolism and insulin secretion, suggesting that variants in the mitochondrial genome may contribute to diabetes susceptibility. In a study of Finnish families ascertained for type 2 diabetes mellitus (T2DM), we genotyped single nucleotide polymorphisms (SNPs) based on phylogenetic networks. These SNPs defined eight major haplogroups and subdivided groups H and U, which are common in Finns. We evaluated association with both diabetes disease status and up to 14 diabetes-related traits for 762 cases, 402 non-diabetic controls, and 465 offspring of genotyped females. Haplogroup J showed a trend toward association with T2DM affected status (OR 1.69, P=0.056) that became slightly more significant after excluding cases with affected fathers (OR 1.77, P=0.045). We also genotyped non-haplogroup-tagging SNPs previously reported to show evidence for association with diabetes or related traits. Our data support previous evidence for association of T16189C with reduced ponderal index at birth and also show evidence for association with reduced birthweight but not with diabetes status. Given the multiple tests performed and the significance levels obtained, this study suggests that mitochondrial genome variants may play at most a modest role in glucose metabolism in the Finnish population. Furthermore, our data do not support a reported maternal inheritance pattern of T2DM but instead show a strong effect of recall bias. C1 Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA. NHGRI, Genome Technol Branch, Bethesda, MD 20892 USA. Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 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. Natl Publ Hlth Inst, Diabet & Genet Epidemiol Unit, Dept Epidemiol & Hlth Promot, Helsinki, Finland. Natl Publ Hlth Inst, Dept Biochem, Helsinki, Finland. Univ Helsinki, Dept Publ Hlth, Helsinki, Finland. So Ostrobothnia Cent Hosp, Seinajoki, Finland. RP Mohlke, KL (reprint author), Univ N Carolina, Dept Genet, 4109-F Neurosci Res Bldg,103 Mason Farm Rd,CB 726, Chapel Hill, NC 27599 USA. EM mohlke@med.unc.edu FU Intramural NIH HHS; NHGRI NIH HHS [HG00376]; NIDDK NIH HHS [DK29867, DK62370, R01 DK029867, DK27619] NR 56 TC 44 Z9 44 U1 2 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD NOV PY 2005 VL 118 IS 2 BP 245 EP 254 DI 10.1007/s00439-005-0046-4 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 993YN UT WOS:000233996300010 PM 16142453 ER PT J AU Yampolsky, LY Kondrashov, FA Kondrashov, AS AF Yampolsky, LY Kondrashov, FA Kondrashov, AS TI Distribution of the strength of selection against amino acid replacements in human proteins SO HUMAN MOLECULAR GENETICS LA English DT Article ID ANCESTRAL POPULATION SIZES; SPECIES DIVERGENCE TIMES; SYNONYMOUS CODON USAGE; HUMAN GENETIC-DISEASE; HUMAN GENOME; EVOLUTION; SUBSTITUTION; DATABASE; DNA; CHIMPANZEES AB The impact of an amino acid replacement on the organism's fitness can vary from lethal to selectively neutral and even, in rare cases, beneficial. Substantial data are available on either pathogenic or acceptable replacements. However, the whole distribution of coefficients of selection against individual replacements is not known for any organism. To ascertain this distribution for human proteins, we combined data on pathogenic missense mutations, on human non-synonymous SNPs and on human-chimpanzee divergence of orthologous proteins. Fractions of amino acid replacements which reduce fitness by > 10(-2), 10(-2)-10(-4), 10(-4)-10(-5) and < 10(-5) are 25, 49, 14 and 12%, respectively. On average, the strength of selection against a replacement is substantially higher when chemically dissimilar amino acids are involved, and the Grantham's index of a replacement explains 35% of variance in the average logarithm of selection coefficients associated with different replacements. Still, the impact of a replacement depends on its context within the protein more than on its own nature. Reciprocal replacements are often associated with rather different selection coefficients, in particular, replacements of non-polar amino acids with polar ones are typically much more deleterious than replacements in the opposite direction. However, differences between evolutionary fluxes of reciprocal replacements are only weakly correlated with the differences between the corresponding selection coefficients. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. E Tennessee State Univ, Dept Biol Sci, Johnson City, TN 37614 USA. Univ Calif San Diego, Sect Ecol Behav & Evolut, La Jolla, CA 92093 USA. RP Kondrashov, AS (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM kondrashov@ncbi.nlm.nih.gov RI Kondrashov, Fyodor Alexeevich/H-6331-2015 OI Kondrashov, Fyodor Alexeevich/0000-0001-8243-4694 NR 38 TC 65 Z9 65 U1 0 U2 7 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 NOV 1 PY 2005 VL 14 IS 21 BP 3191 EP 3201 DI 10.1093/hmg/ddi350 PG 11 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 976QR UT WOS:000232748800008 PM 16174645 ER PT J AU Zhu, JL Madsen, KM Vestergaard, M Olesen, AV Basso, O Olsen, J AF Zhu, JL Madsen, KM Vestergaard, M Olesen, AV Basso, O Olsen, J TI Paternal age and congenital malformations SO HUMAN REPRODUCTION LA English DT Article DE abnormalities; Down's syndrome; paternal age AB BACKGROUND: Spontaneous mutations in germ cells increase with male age, but an association between paternal age and congenital malformations is not well established. We conducted a population-based cohort study to estimate this association. METHODS: A study population of couples and their firstborn children were identified in the Danish Fertility Database between 1980 and 1996 (n = 71 937). Diagnoses of congenital malformations in children were obtained by linkage to the nationwide hospital register (1980-1999). RESULTS: Overall, there were no differences in the prevalence of malformations as a function of paternal age. However, the prevalence of malformations of extremities and syndromes of multiple systems, as well as Down's syndrome, increased with increasing paternal age. For example, in comparison with fathers age 20-29 years, adjusted hazard ratio of syndromes of multiple systems was 1.15 [95% confidence interval (CI) 0.81-1.65] for age 35-39 years, 1.33 (95% CI 0.79-2.25) for age 40-44 years, 1.73 (95% CI 0.82-3.65) for age 45-49 years, and 3.20 (95% CI 1.37-7.48) for age $50 years (test for trend P = 0.01). CONCLUSIONS: Our data suggest that advanced paternal age may be associated with an excess occurrence of some specific malformations. The association could be caused by mutations of the gametes in men induced by biological or environmental factors. C1 Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90095 USA. NIEHS, Epidemiol Branch, Dept Hlth & Human Sev, NIH, Res Triangle Pk, NC 27709 USA. Univ Aarhus, Dept Epidemiol, DK-8000 Aarhus, Denmark. Univ Aarhus, Danish Epidemiol Sci Ctr, DK-8000 Aarhus, Denmark. RP Olsen, J (reprint author), Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, Box 951772, Los Angeles, CA 90095 USA. RI Basso, Olga/E-5384-2010; Vestergaard, Mogens/M-9333-2014 OI Basso, Olga/0000-0001-9298-4921; Vestergaard, Mogens/0000-0001-8830-2174 NR 25 TC 48 Z9 53 U1 1 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD NOV PY 2005 VL 20 IS 11 BP 3173 EP 3177 DI 10.1093/humrep/dei186 PG 5 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 980VG UT WOS:000233045700032 PM 16006461 ER PT J AU Han, SH Quon, MJ Koh, KK AF Han, SH Quon, MJ Koh, KK TI Beneficial vascular and metabolic effects of peroxisome proliferator-activated receptor-alpha activators SO HYPERTENSION LA English DT Review DE fibrates; endothelium; adipose tissue; insulin resistance; cardiovascular diseases ID DENSITY-LIPOPROTEIN CHOLESTEROL; CORONARY-ARTERY-DISEASE; NITRIC-OXIDE SYNTHASE; HUMAN ENDOTHELIAL-CELLS; PPAR-ALPHA; COMBINED HYPERLIPIDEMIA; POSTPRANDIAL LIPEMIA; INSULIN SENSITIVITY; VASOMOTOR FUNCTION; OXIDATIVE STRESS AB Fibric acid is a synthetic ligand of the nuclear receptor peroxisome proliferator-activated receptor (PPAR)-alpha that is highly expressed in skeletal muscle and heart, where it promotes beta-oxidation of fatty acids to mediate hypolipidemic actions. PPAR-alpha regulates expression of key proteins involved in atherogenesis, vascular inflammation, plaque instability, and thrombosis. Thus, PPAR-alpha may exert direct antiatherogenic actions in the vascular wall. Endothelial dysfunction associated with the metabolic syndrome and other insulin-resistant states is characterized by impaired insulin-stimulated nitric oxide production from the endothelium and decreased blood flow to skeletal muscle. Thus, improvement in insulin sensitivity leads to improved endothelial function. This may be an additional mechanism whereby fibrates decrease the incidence of coronary heart disease. Adiponectin is a protein secreted specifically by adipose cells that may couple regulation of insulin sensitivity with energy metabolism and serve to link obesity with insulin resistance. In this review, we discuss the mechanisms underlying the vascular and metabolic effects of fibrates that may act synergistically to prevent or regress atherosclerosis and coronary heart disease. C1 Gil Heart Ctr, Div Cardiol, Gachon Med Sch, Inchon 405760, South Korea. NIH, Diabet Unit, Clin Invest Lab, NCCAM, Bethesda, MD 20892 USA. RP Koh, KK (reprint author), Gil Heart Ctr, Div Cardiol, Gachon Med Sch, 1198 Kuwol Dong, Inchon 405760, South Korea. EM kwangk@ghil.com RI Quon, Michael/B-1970-2008 NR 66 TC 64 Z9 68 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD NOV PY 2005 VL 46 IS 5 BP 1086 EP 1092 DI 10.1161/01.HYP.0000187900.36455.4c PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 987VG UT WOS:000233544900003 PM 16230515 ER PT J AU Cai, T AF Cai, T TI Are IA-2 and RESP18 involved in trait of blood pressure? SO HYPERTENSION LA English DT Letter ID HYPERTENSION C1 Natl Inst Dent & Craniofacial Res, NIH, Expt Med Sect, Oral Infect & Immun Branch, Bethesda, MD USA. RP Cai, T (reprint author), Natl Inst Dent & Craniofacial Res, NIH, Expt Med Sect, Oral Infect & Immun Branch, Bethesda, MD USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD NOV PY 2005 VL 46 IS 5 BP E18 EP E18 DI 10.1161/01.HYP.0000188174.83586.20 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 987VG UT WOS:000233544900409 PM 16216981 ER PT J AU Bornstein, MH Giusti, Z Leach, DB Venuti, P AF Bornstein, MH Giusti, Z Leach, DB Venuti, P TI Maternal reports of adaptive behaviours in young children: Urban-rural and gender comparisons in Italy and United States SO INFANT AND CHILD DEVELOPMENT LA English DT Review DE adaptive behaviour; culture; region; gender ID SEX-DIFFERENCES; COMMUNICATIVE DEVELOPMENT; INFANT TEMPERAMENT; ACTIVITY LEVEL; EXPECTATIONS; LANGUAGE; MOTHER; VARIABILITY; INVENTORY; COGNITION AB We compared how 182 Italian and US American urban and rural firstborn 20-month-old girls and boys cope with the demands of their environment through their adaptive behaviours in everyday activities. Using the Vineland Adaptive Behaviour Scales, we collected maternal reports of children's communication, daily living, socialization, and motor skills. Three sets of main effects (and no interactions) emerged. With respect to country, Italian children scored higher than US American children in adaptive communication and motor skills. With respect to region, urban children showed higher adaptive motor skills than rural children, and rural children showed higher adaptive daily living skills than urban children. Finally, with respect to gender, girls scored higher on an adaptive behaviour composite as well as adaptive communication skills, but boys higher in adaptive motor skills. We set these country, region, and gender main effects in the context of a discussion of developing adaptive behaviours in young children. Copyright (c) 2005 John Wiley & Sons, Ltd. C1 NICHHD, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Bornstein, MH (reprint author), NICHHD, NIH, Dept Hlth & Human Serv, Suite 8030,6705 Rockledge Dr, Bethesda, MD 20892 USA. EM Marc_H_Bornstein@nih.gov RI Putnick, Diane/B-1707-2009; OI Putnick, Diane/0000-0002-6323-749X NR 115 TC 7 Z9 7 U1 1 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1522-7227 J9 INFANT CHILD DEV JI Infant Child Dev. PD NOV PY 2005 VL 14 IS 4 BP 403 EP 424 DI 10.1002/icd.414 PG 22 WC Psychology, Developmental SC Psychology GA 986AC UT WOS:000233419700005 ER PT J AU Darby, C Ananth, SL Tan, L Hinnebusch, BJ AF Darby, C Ananth, SL Tan, L Hinnebusch, BJ TI Identification of gmhA, a Yersinia pestis gene required for flea blockage, by using a Caenorhabditis elegans biofilm system SO INFECTION AND IMMUNITY LA English DT Article ID INNER-CORE LIPOPOLYSACCHARIDE; PIGMENTATION PHENOTYPE; GENOME SEQUENCE; CAUSATIVE AGENT; PLAGUE; PSEUDOTUBERCULOSIS; BACTERIA; BIOSYNTHESIS; CONSTRUCTION; TRANSMISSION AB Yersinia pestis, the cause of bubonic plague, blocks feeding by its vector, the flea. Recent evidence indicates that blockage is mediated by an in vivo biofilm. Y. pestis and the closely related Yersinia pseudotuberculosis also make biofilms on the cuticle of the nematode Caenorhabditis elegans, which block this laboratory animal's feeding. Random screening of Y. pseudotuberculosis transposon insertion mutants with a C. elegans biofilm assay identified gmhA as a gene required for normal biofilms. gmhA encodes phosphoheptose isomerase, an enzyme required for synthesis of heptose, a conserved component of lipopolysaccharide and lipooligosaccharide. A Y. pestis gmhA mutant was constructed and was severely defective for C. elegans biofilm formation and for flea blockage but only moderately defective in an in vitro biofilm assay. These results validate use of the C elegans biofilm system to identify genes and pathways involved in Y. pestis flea blockage. C1 Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA. NIAID, Rocky Mt Labs, Hamilton, MT USA. RP Darby, C (reprint author), Univ Alabama, Dept Microbiol, 1530 3rd Ave S,BBRB Box 19, Birmingham, AL 35294 USA. EM creg@uab.cdu FU NIAID NIH HHS [AI026195, AI057512, R01 AI026195, R01 AI057512, R56 AI057512] NR 26 TC 48 Z9 53 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 NOV PY 2005 VL 73 IS 11 BP 7236 EP 7242 DI 10.1128/IAI.73.11.7236.7242.2005 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 977WI UT WOS:000232833800018 PM 16239518 ER PT J AU Arakawa, T Komesu, A Otsuki, H Sattabongkot, J Udomsangpetch, R Matsumoto, Y Tsuji, N Wu, YM Torii, M Tsuboi, T AF Arakawa, T Komesu, A Otsuki, H Sattabongkot, J Udomsangpetch, R Matsumoto, Y Tsuji, N Wu, YM Torii, M Tsuboi, T TI Nasal immunization with a malaria transmission-blocking vaccine candidate, Pfs25, induces complete protective immunity in mice against field isolates of Plasmodium falciparum SO INFECTION AND IMMUNITY LA English DT Article ID MEROZOITE SURFACE PROTEIN-1; CHOLERA-TOXIN; INTRANASAL IMMUNIZATION; ANTIBODIES; IMMUNOGENICITY; INDUCTION; ANTIGEN; VIVAX; DNA; EXPRESSION AB Malaria transmission-blocking vaccines based on antigens expressed in sexual stages of the parasites are considered one promising strategy for malaria control. To investigate the feasibility of developing noninvasive mucosal transmission-blocking vaccines against Plasmodium falciparum, intranasal immunization experiments with Pichia pastoris-expressed recombinant Pfs25 proteins were conducted. Mice intranasally immunized with the Pfs25 proteins in the presence of a potent mucosal adjuvant cholera toxin induced robust systemic as well as mucosal antibodies. All mouse immunoglobulin G (IgG) subclasses except IgG3 were found in serum at comparable levels, suggesting that the immunization induced mixed Th1 and Th2 responses. Consistent with the expression patterns of the Pfs25 proteins in the parasites, the induced immune sera specifically recognized ookinetes but not gametocytes. In addition, the immune sera recognized Pfs25 proteins with the native conformation but not the denatured forms, indicating that mucosal immunization induced biologically active antibodies capable of recognizing conformational epitopes of native Pfs25 proteins. Feeding Anopheles dirus mosquitoes with a mixture of the mouse immune sera and gametocytemic blood derived from patients infected with P. falciparum resulted in complete interference with oocyst development in mosquito midguts. The observed transmission-blocking activities were strongly correlated with specific serum antibody titers. Our results demonstrated for the first time that a P. falciparum transmission-blocking vaccine candidate is effective against field-isolated parasites and may justify the investigation of noninvasive mucosal vaccination regimens for control of malaria, it prototypical mucosa-unrelated mosquito-borne parasitic disease. C1 Ehime Univ, Cell Free Sci & Technol Res Ctr, Matsuyama, Ehime 7908577, Japan. Univ Ryukyus, Ctr Mol Biosci, Div Mol Microbiol, Nishihara, Okinawa 9030213, Japan. Ehime Univ, Sch Med, Dept Mol Parasitol, Toon, Ehime 7910295, Japan. Armed Forces Res Inst Med Sci, Dept Entomol, Bangkok 10400, Thailand. Mahidol Univ, Fac Sci, Dept Pathobiol, Bangkok 10400, Thailand. Univ Tokyo, Grad Sch Agr & Life Sci, Lab Global Anim Resource Sci, Bunkyo Ku, Tokyo 1138657, Japan. Natl Agr Res Org, Natl Inst Anim Hlth, Parasit Dis Lab, Tsukuba, Ibaraki 3050856, Japan. NIAID, Malaria Vaccine Dev Branch, NIH, Rockville, MD 20852 USA. RP Tsuboi, T (reprint author), Ehime Univ, Cell Free Sci & Technol Res Ctr, 3 Bunkyo Cho, Matsuyama, Ehime 7908577, Japan. EM tsuboi@ccr.ehime-u.ac.jp NR 33 TC 47 Z9 50 U1 9 U2 31 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 NOV PY 2005 VL 73 IS 11 BP 7375 EP 7380 DI 10.1128/IAI.73.11.7375-7380.2005 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 977WI UT WOS:000232833800036 PM 16239536 ER PT J AU Peng, DX Hong, WZ Choudhury, BP Carlson, RW Gu, XX AF Peng, DX Hong, WZ Choudhury, BP Carlson, RW Gu, XX TI Moraxella catarrhalis bacterium without endotoxin, a potential vaccine candidate SO INFECTION AND IMMUNITY LA English DT Article ID NEISSERIA-MENINGITIDIS MUTANT; OUTER-MEMBRANE PROTEIN; BRANHAMELLA-CATARRHALIS; ESCHERICHIA-COLI; LIPID-A; LIPOPOLYSACCHARIDE BIOSYNTHESIS; SEROTYPE-A; HAEMOPHILUS-INFLUENZAE; ACID TRANSFERASE; IMMUNE-RESPONSE AB Lipooligosaccharide (LOS) is a major surface component of Moraxella catarrhalis and a possible virulence factor in the pathogenesis of human infections caused by this organism. The presence of LOS on the bacterium is an obstacle to the development of vaccines derived from whole cells or outer membrane components of the bacterium. An lpxA gene encoding UDP-N-acetylglucosamine acyltransferase responsible for the first step of lipid A biosynthesis was identified by the construction and characterization of an isogenic M. catarrhalis lpxA mutant in strain O35E. The resulting mutant was viable despite the complete loss of LOS. The mutant strain showed significantly decreased toxicity by the Limulus amebocyte lysate assay, reduced resistance to normal human serum, reduced adherence to human epithelial cells, and enhanced clearance in lungs and nasopharynx in a mouse aerosol challenge model. Importantly, the mutant elicited high levels of antibodies with bactericidal activity and provided protection against a challenge with the wild-type strain. These data suggest that the null LOS mutant is attenuated and may be a potential vaccine candidate against M. catarrhalis. C1 Natl Inst Deafness & Other Commun Disorders, Vaccine Res Sect, Rockville, MD 20850 USA. Univ Georgia, Complex Carbohydrate Res Ctr, Athens, GA 30602 USA. RP Gu, XX (reprint author), 5 Res Court,Room 2A31, Rockville, MD 20850 USA. EM guxx@nidcd.nih.gov FU Intramural NIH HHS NR 45 TC 46 Z9 48 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 NOV PY 2005 VL 73 IS 11 BP 7569 EP 7577 DI 10.1128/IAI.73.11.7569-7577.2005 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 977WI UT WOS:000232833800060 PM 16239560 ER PT J AU Hsieh, JC Tham, DM Feng, WJ Huang, F Embaie, S Liu, KY Dean, D Hertle, R FitzGerald, DJ Mrsny, RJ AF Hsieh, JC Tham, DM Feng, WJ Huang, F Embaie, S Liu, KY Dean, D Hertle, R FitzGerald, DJ Mrsny, RJ TI Intranasal immunization strategy to impede pilin-mediated binding of Pseudomonas aeruginosa to airway epithelial cells SO INFECTION AND IMMUNITY LA English DT Article ID EXOTOXIN-A; CYSTIC-FIBROSIS; RECEPTOR-BINDING; ANTIBODY-RESPONSES; CONJUGATE VACCINE; VIRULENCE FACTORS; YOUNG-CHILDREN; STRAINS PAK; IV PILIN; ADHERENCE AB Prevention of pulmonary Pseudomonas aeruginosa infections represents a critical unmet medical need for cystic fibrosis (CF) patients. We have examined the tenet that a mucosal immunization approach can reduce interactions of a piliated form of this opportunistic pathogen with respiratory epithelial cells. Vaccinations were performed using ntPEpilinPAK, a protein chimera composed of a nontoxic form of P. aeruginosa exotoxin A (OPE), where the C-terminal loop amino acid sequence of the PAK strain pilin protein was inserted in place of the ntPE Ib domain. Intranasal (i.n.) immunization of BALB/c mice with ntPEpilinPAK generated both serum and saliva immune responses. A series of in vitro studies showed that diluted samples of saliva obtained from immunized mice reduced pilin-dependent P. aeruginosa binding to polarized human tracheal epithelial cells, protected human pulmonary epithelial cells from cytotoxic actions associated with bacterial challenge, and reduced exotoxin A toxicity. Overall, i.n. administration of ntPEpilinPAK induced mucosal and systemic immune responses that may be beneficial for blocking early stage adhesion and/or infection events of epithelial cell-P. aeruginosa interactions at oropbaryngeal surfaces. C1 Trinity BioSyst Inc, Menlo Pk, CA 94025 USA. Univ Calif San Francisco, Sch Med, Dept Med, San Francisco, CA 94143 USA. Childrens Hosp Oakland, Res Inst, Oakland, CA 94609 USA. NCI, Biotherapy Sect, Mol Biol Lab, CCR, Bethesda, MD 20892 USA. Univ Tubingen, Inst Microbiol & Membrane Physiol, D-72076 Tubingen, Germany. RP Mrsny, RJ (reprint author), Trinity BioSyst Inc, 1455 Adams Dr,Suite 1317, Menlo Pk, CA 94025 USA. EM rmrsny@trinitybiosystems.com FU NIAID NIH HHS [R01 AI039499, AI39499] NR 70 TC 3 Z9 3 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 NOV PY 2005 VL 73 IS 11 BP 7705 EP 7717 DI 10.1128/IAI.73.11.7705-7717.2005 PG 13 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 977WI UT WOS:000232833800075 PM 16239575 ER PT J AU Robuck, PR Wurzelmann, JI AF Robuck, PR Wurzelmann, JI TI Understanding the drug development process SO INFLAMMATORY BOWEL DISEASES LA English DT Article; Proceedings Paper CT Conference on IBD Clinical Trials Course - Principles and Practice CY MAR 11-12, 2005 CL St Petersburg, FL DE drug development; Food and Drug Administration; Investigational New Drug; National Institutes of Health; New Drug Application AB In the United States, new drug development is a complex, highly regulated process that often involves academic institutions, the pharmaceutical industry, and government agencies. Much of the primary and clinical research conducted in the United States is funded by the National Institutes of Health. The Food and Drug Administration (FDA) provides regulatory review and oversight of the drug development process. The Investigational New Drug application is the primary mechanism that the FDA uses to regulate clinical testing in humans. A New Drug Application summarizing all of the data necessary to perform risk/benefit analysis of the new drug is submitted to the FDA for review and approval once sufficient testing has been completed. Recent research into the pathogenesis of inflammatory bowel disease has yielded numerous drug targets resulting in a multitude of molecules and biologic agents under varying stages of development and a consequent need for clinical testing. A thorough understanding of the regulatory development process and the National Institutes of Health funding process is necessary for any investigator involved in clinical trials. C1 NIDDK, Bethesda, MD 20892 USA. GlaxoSmithKline Inc, Res Triangle Pk, NC USA. RP Robuck, PR (reprint author), Crohns & Colitis Fdn Amer, 386 Pk Ave S,17th Floor, New York, NY 10016 USA. EM mmerrick@ccfa.org NR 5 TC 4 Z9 4 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD NOV PY 2005 VL 11 SU 1 BP S13 EP S16 DI 10.1097/01.MIB.0000184851.46440.a3 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 984RM UT WOS:000233322000003 PM 16254477 ER PT J AU Sandler, RS Lewis, JD Robuck, PR Sands, BE AF Sandler, RS Lewis, JD Robuck, PR Sands, BE TI Funding and grantsmanship SO INFLAMMATORY BOWEL DISEASES LA English DT Article; Proceedings Paper CT Conference on IBD Clinical Trials Course - Principles and Practice CY MAR 11-12, 2005 CL St Petersburg, FL DE Crohn's & Colitis Foundation of America; National Institutes of Health; research funding; research grant ID CLINICAL-RESEARCH AB Medical research funding in the United States has 4 predominant sources: the federal government; the pharmaceutical industry; institutions; and private foundations. In each case, the grant application process is the first step in obtaining funding. Successful grant applications are logical, organized, and easy to read. The research question should be both specific and significant. Comprehensive and detailed study methods addressing the study population, timeline, and data collection and management increase the likelihood of obtaining funding. Funding for inflammatory bowel disease preclinical and clinical research is available from the National Institutes of Health and Crohn's & Colitis Foundation of America. C1 Univ N Carolina, Chapel Hill, NC USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. NIDDK, Bethesda, MD USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Sandler, RS (reprint author), Cohns & Colitis Fdn Amer, 386 Pk Ave S,17th Floor, New York, NY 10016 USA. EM mmerrick@ccfa.org NR 3 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD NOV PY 2005 VL 11 SU 1 BP S34 EP S37 DI 10.1097/01.MIB.0000184847.54063.fe PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 984RM UT WOS:000233322000007 ER PT J AU Tremaine, WJ Carlson, MR Isaacs, KL Motil, KJ Robuck, PR Wurzelmann, JI AF Tremaine, WJ Carlson, MR Isaacs, KL Motil, KJ Robuck, PR Wurzelmann, JI TI Ethical issues, safety, and data integrity in clinical trials SO INFLAMMATORY BOWEL DISEASES LA English DT Article; Proceedings Paper CT Conference on IBD Clinical Trials Course - Principles and Practice CY MAR 11-12, 2005 CL St Petersburg, FL ID CONFLICTS-OF-INTEREST AB Published in 1974, the Belmont Report established the ethical principles for conducting clinical research in the United States. The essential concepts are respect for the research participant, beneficence for society at large, and justice (equal access to participation and equal treatment) toward subjects in a research study. These principles are applied through the use of informed consent, risk/benefit assessment, and the impartial selection of study subjects. Strict adherence to these criteria often results in conflicts of interest, which the investigator must anticipate and manage. Investigators must also be thoroughly acquainted with the principles of Good Clinical Practice and regulatory requirements. Recent implementation of the Privacy Rule now requires the investigator to protect not only the safety but the privacy of the research subject. While the regulatory obligations can appear onerous, strict compliance results in clinical research that is safe, scientifically sound, and ethical. C1 Mayo Clin, Coll Med, Rochester, MN USA. EntreMeDica Inc, Encinitas, CA USA. Univ N Carolina, Chapel Hill, NC USA. Baylor Coll Med, Houston, TX 77030 USA. NIDDK, Bethesda, MD 20892 USA. GlaxoSmithKline Inc, Res Triangle Pk, NC USA. RP Tremaine, WJ (reprint author), Crohns & Colitis Fdn Amer, 386 Pk Ave S,17th Floor, New York, NY 10016 USA. EM mmerrick@ccfa.org NR 6 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD NOV PY 2005 VL 11 SU 1 BP S17 EP S21 DI 10.1097/01.MIB.0000184850.46440.ea PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 984RM UT WOS:000233322000004 PM 16254478 ER PT J AU Vadyvaloo, V Otto, M AF Vadyvaloo, V Otto, M TI Molecular genetics of Staphylococcus epidermidis biofilms on indwelling medical devices SO INTERNATIONAL JOURNAL OF ARTIFICIAL ORGANS LA English DT Article DE Staphylococus epidermidis; Biofilms; PIA ID POLYSACCHARIDE INTERCELLULAR ADHESIN; COAGULASE-NEGATIVE STAPHYLOCOCCI; CATHETER-ASSOCIATED INFECTION; FIBRINOGEN-BINDING-PROTEIN; PHENOL-SOLUBLE MODULINS; SEQUENCE ELEMENT IS256; SIGMA-FACTOR SIGMA(B); TEICHOIC-ACID; ICA LOCUS; FIBRONECTIN-BINDING AB Staphylococcus epidermidis is an opportunistic pathogen associated with foreign body infections and nosocomial sepsis. The pathogenicity of S. epidermidis is mostly due to its ability to colonize indwelling polymeric devices and form a thick, multilayered biofilm. Biofilm formation is a major problem in treating S. epidermidis infection as biofilms provide significant resistance to antibiotics and to components of the innate host defenses. Various cell surface associated bacterial factors play a role in adherence and accumulation of the biofilm such as the polysaccharide intercellular adhesin and the autolysin AtIE. Furthermore, recent studies have shown that global regulators such as the agr quorum sensing system, the transcriptional regulator sarA and the alternative sigma factor sigB have an important function in the regulation of biofilm formation. Understanding the many complex mechanisms involved in biofilm formation is a key factor in the search for new anti-staphylococcal therapeutics. (Int J Artif Organs 2005; 28: 1069-78) C1 NIAID, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Vadyvaloo, V (reprint author), NIAID, Rocky Mt Labs, NIH, 903 S 4th St, Hamilton, MT 59840 USA. OI Otto, Michael/0000-0002-2222-4115 NR 93 TC 38 Z9 42 U1 3 U2 7 PU WICHTIG EDITORE PI MILAN PA 72/74 VIA FRIULI, 20135 MILAN, ITALY SN 0391-3988 J9 INT J ARTIF ORGANS JI Int. J. Artif. Organs PD NOV PY 2005 VL 28 IS 11 BP 1069 EP 1078 PG 10 WC Engineering, Biomedical; Transplantation SC Engineering; Transplantation GA 991LF UT WOS:000233814800004 PM 16353113 ER PT J AU Cote, LR Bornstein, MH AF Cote, LR Bornstein, MH TI Child and mother play in cultures of origin, acculturating cultures, and cultures of destination SO INTERNATIONAL JOURNAL OF BEHAVIORAL DEVELOPMENT LA English DT Article ID UNITED-STATES; SYMBOLIC PLAY; AMERICAN PARENTS; PRETEND PLAY; BEHAVIOR; JAPAN; UNIVERSAL; TODDLERS; HOME AB Immigrant (Japanese and South Americans in the United States) families' play was compared to play in families in their countries of origin (Japan and Argentina, respectively) and in a common country of destination (European Americans in the United States). Two hundred and forty 20-month-old children and their mothers participated. Generally, the play of immigrant children and mothers was similar to European American children's and mothers' play. Japanese and Argentine children engaged in more symbolic play, whereas immigrant children engaged in more exploratory play. Likewise, South American immigrant mothers demonstrated and solicited more exploratory play than Argentine mothers. Japanese mothers solicited more symbolic play, and Argentine mothers demonstrated more symbolic play than immigrant mothers. The findings from this study provide insight into the nature of child and mother play generally and that of immigrant children and their mothers specifically and shed light on the parenting climate in which immigrant children are reared. C1 NICHHD, NIH, Bethesda, MD 20892 USA. RP Bornstein, MH (reprint author), NICHHD, NIH, Suite 8030,6705 Rockledge Dr, Bethesda, MD 20892 USA. EM Marc_H_Bornstein@nih.gov NR 63 TC 10 Z9 10 U1 1 U2 6 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0165-0254 J9 INT J BEHAV DEV JI Int. J. Behav. Dev. PD NOV PY 2005 VL 29 IS 6 BP 479 EP 488 DI 10.1080/01650250500147006 PG 10 WC Psychology, Developmental SC Psychology GA 986UJ UT WOS:000233474900002 ER PT J AU Ronckers, CM McCarron, P Ron, E AF Ronckers, CM McCarron, P Ron, E TI Thyroid cancer and multiple primary tumors in the SEER cancer registries SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE multiple primary cancers; thyroid cancer; epidemiology; radiotherapy ID SALIVARY-GLAND TUMORS; RENAL-CELL CARCINOMA; POOLED ANALYSIS; EPIDEMIOLOGIC EVIDENCE; PRIMARY BREAST; FOLLOW-UP; RADIATION; RISK; POPULATION; ACRYLAMIDE AB Thyroid cancer incidence rates have increased steadily in the United States and elsewhere. Radiation exposure at a young age is a strong risk factor, but otherwise the etiology is unclear. To explore etiologic clues, we studied the risk of thyroid cancer after an earlier primary cancer, as well as the risk of developing multiple primaries after an earlier thyroid cancer in the U.S. Surveillance, Epidemiology and End-Results (SEER) cancer registries program (1973-2000). In 2,036,597 patients diagnosed with any invasive cancer who survived for a minimum of 2 months, we observed a 42% increased risk compared to the general population for second thyroid cancer based on 1,366 cases (95% confidence interval (CI) = 35-50%; excess absolute risk (EAR) = 0.38/ 10,000 person-years (PY)). Elevated risks were observed after most cancer sites studied. The most pronounced excess (observed/ expected (O/E) = 2.86) was seen for second thyroid cancers detected in the year after diagnosis of the first cancer. Among 29,456 2-month thyroid cancer survivors, 2,214 second cancers occurred (O/E = 1.11, 95% CI = 1.06-1.15; EAR = 7.64/10,000 PY). Again, the highest risk was seen in the first year (O/E = 1.26). Patients < 40 years of age at diagnosis of thyroid cancer had a 39% increased risk of a second cancer, whereas for older patients the risk was elevated 6%. We observed consistently increased risks for cancers of the breast, prostate, and kidney, and a likely radiation treatment-related excess of leukemia. Based on small numbers of cases, cancers of the salivary glands, trachea, scrotum, adrenal glands, and brain and central nervous system (CNS) also occurred in excess. A decreased risk was observed for smoking-related malignancies. Thyroid cancer is associated with primary cancers of many different organs. Although enhanced medical surveillance likely plays a role, 2-way, positive associations between thyroid cancer and cancers of the breast, prostate, kidney, salivary glands, brain and CNS, scrotum, and leukemia suggest etiologic similarities and possible treatment effects. (c) 2005 Wiley-Liss, Inc. C1 NIH, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, DHHS,NCI, Bethesda, MD 20892 USA. NIH, Div Canc Control & Populat Sci, DHHS, NCI, Bethesda, MD 20892 USA. Queens Univ Belfast, Dept Epidemiol & Publ Hlth, No Ireland Canc Registry, Belfast, Antrim, North Ireland. RP Ronckers, CM (reprint author), NIH, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, DHHS,NCI, Bldg 10, Bethesda, MD 20892 USA. EM ronckerc@mail.nih.gov NR 52 TC 74 Z9 78 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD NOV 1 PY 2005 VL 117 IS 2 BP 281 EP 288 DI 10.1002/ijc.21064 PG 8 WC Oncology SC Oncology GA 968VL UT WOS:000232190900016 PM 15880372 ER PT J AU Devesa, SS Bray, F Vizcaino, AP Parkin, DM AF Devesa, SS Bray, F Vizcaino, AP Parkin, DM TI International lung cancer trends by histologic type: male : female differences diminishing and adenocarcinoma rates rising SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE lung cancer incidence; histology; trends ID CIGARETTE-SMOKING; UNITED-STATES; YOUNG MEN; WOMEN; EPIDEMIOLOGY; EUROPE; COHORT AB Lung cancer rates have peaked among men in many areas of the world, but rates among women continue to rise. Most lung cancers are squamous cell carcinoma, small cell carcinoma, or adenocarcinoma; trends vary according to type. We compiled population-based morphology-specific incidence data from registries contributing to the International Agency for Research on Cancer (IARC) databases. Unspecified cancers and carcinomas were reallocated based on a registry, time period, sex and age group-specific basis. Where available, data from several registries within a country were pooled for analysis. Rates per 100,000 person-years for 1980-1982 to 1995-1997 were age-adjusted by the direct method using the world standard. Squamous cell carcinoma rates among males declined 30% or more in North America and some European countries while changing less dramatically in other areas; small cell carcinoma rates decreased less rapidly. Squamous and small cell carcinoma rates among females generally rose, with the increases especially pronounced in the Netherlands and Norway. In contrast, adenocarcinoma rates rose among males and females in virtually all areas, with the increases among males exceeding 50% in many areas of Europe; among females, rates also rose rapidly and more than doubled in Norway, Italy and France. Rates of all lung cancer types among women and adenocarcinoma among men continue to rise despite declining cigarette use in many Western countries and shifts to filtered/low-tar cigarettes. Renewed efforts toward cessation and prevention are mandatory to curb the prevalence of cigarette smoking and to reduce lung cancer rates eventually. (c) 2005 Wiley-Liss, Inc. C1 NIH, Biostat Branch, Div Canc Epidemiol & Genet, NCI, Bethesda, MD 20892 USA. Int Agcy Res Canc, F-69372 Lyon, France. RP Devesa, SS (reprint author), NIH, Biostat Branch, Div Canc Epidemiol & Genet, NCI, Bldg 10, Bethesda, MD 20892 USA. EM devesas@exchange.nih.gov NR 37 TC 367 Z9 379 U1 2 U2 18 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD NOV 1 PY 2005 VL 117 IS 2 BP 294 EP 299 DI 10.1002/ijc.21183 PG 6 WC Oncology SC Oncology GA 968VL UT WOS:000232190900018 PM 15900604 ER PT J AU Boyce, EA Kohn, EC AF Boyce, EA Kohn, EC TI Ovarian cancer in the proteomics era: diagnosis, prognosis, and therapeutics targets SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER LA English DT Article DE biomarker; mass spectroscopy; ovarian cancer; proteomics ID PHASE PROTEIN MICROARRAYS; BREAST-CANCER; SERUM; DISEASE; MARKERS; TECHNOLOGIES; MANAGEMENT; CARCINOMA; SPECIMENS; WOMEN AB Ovarian cancer is clinically quiet as it plants seeds of metastases in the peritoneal cavity, even during early stages when there is highest potential for cure. The only available biomarker is CA125, which has an unacceptably low sensitivity and specificity for diagnostic use. Highly sensitive and specific tools to further optimize early diagnosis and treatment are needed. We propose that proteomic technologies have an important role to play in the development of these tools. Mass spectrometry platforms, such as surface-enhanced laser desorption/ionization time-of-flight, may be used to mine patient's serum for proteomic signatures that are shed by tumor and stroma. Such signatures could serve as a diagnostic tool during early-stage disease and as a remission-monitoring tool in later-stage disease. Reverse-phase protein microarrays are a new microproteomic tool to profile signaling pathways in ovarian cancer, thus identifying therapeutic targets while simultaneously suggesting prognostic indicators. Proteomic technologies have the capacity to build upon our genomic and clinical understanding of ovarian cancer by moving the focal point to the tumor and its microenvironment. This unique proteomic vantage point allows the creation of tools that will aid clinicians in making rational decisions in the diagnosis and treatment of women with ovarian cancer. C1 NCI, Pathol Lab, Mol Signaling Sect, Ctr Canc Res, Bethesda, MD 20892 USA. RP Kohn, EC (reprint author), NCI, Pathol Lab, Mol Signaling Sect, Ctr Canc Res, 10 Ctr Dr,MSC 1500, Bethesda, MD 20892 USA. EM ek1b@nih.gov OI Carter, Ebony/0000-0002-7620-4929 NR 30 TC 25 Z9 26 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1048-891X J9 INT J GYNECOL CANCER JI Int. J. Gynecol. Cancer PD NOV-DEC PY 2005 VL 15 SU 3 BP 266 EP 273 DI 10.1111/j.1525-1438.2005.00434.x PG 8 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 991HQ UT WOS:000233803600014 PM 16343243 ER PT J AU Duncan, CC Kosmidis, MH Mirsky, AF AF Duncan, CC Kosmidis, MH Mirsky, AF TI Closed head injury-related information processing deficits: An event-related potential analysis SO INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY LA English DT Article; Proceedings Paper CT 12th World Congress of Psychophysiology of the International-Organization-of-Psychophysiology CY SEP 18-23, 2004 CL Thessaloniki, GREECE SP Int Org Psychophysiol DE closed head injury; event-related brain potentials; ERP; P300; N200; N100; information processing; attention; reaction tinie; CPT ID TRAUMATIC BRAIN-INJURY; AUDITORY-EVOKED-POTENTIALS; DIFFUSE AXONAL INJURY; RETROGRADE-AMNESIA; ODDBALL TASK; ELECTROPHYSIOLOGICAL EVIDENCE; POSTTRAUMATIC AMNESIA; MISMATCH NEGATIVITY; CEREBRAL CONCUSSION; NOVELTY DETECTION AB Event-related potentials (ERPs) can elucidate aspects of sensory and cognitive processing that have been compromised due to closed head injury. We present the results of two investigations, one previously unreported, in which we used ERPs to evaluate information processing in head-injury survivors. In the first study, We used visual and auditory reaction time tasks differing in attentional demands to assess processing after head trauma. We found numerous changes in auditory processing in survivors: longer reaction times (but normal accuracy), longer N200 and P300 latencies, and reduced N100 and N200 amplitudes. In contrast, on visual tasks, only reduced N200 amplitude distinguished survivors and controls. To increase attentional demands, in a second study, we administered the continuous performance test (CPT). Survivors performed with lower accuracy than controls on Visual and auditory tasks, and their ERPs were characterized by smaller Visual and auditory N200s and P300s and smaller auditory N100s. We also present a synthesis, derived from a review of the literature, of closed head-injury effects on ERPs. Our own findings are in agreement with that synthesis. Namely, cognitive ERP components are more sensitive than sensory components to the effects of trauma. Specifically, in survivors, the amplitudes of N200 and P300 are often reduced, and their latencies prolonged. In general, as compared with visual ERPs, auditory ERPs may be more Susceptible to the effects of closed head injury, suggesting that the auditory processing system is more Vulnerable than the visual system. We conclude by discussing the potential use Of ERPs to monitor clinical course and recovery in survivors of closed head injury. (c) 2005 Elsevier B.V. All rights reserved. C1 NIMH, SCEN, NIH, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Psychiat, Clin Psychophysiol & Psychopharmacol, Bethesda, MD 20814 USA. Aristotle Univ Thessaloniki, Dept Psychol, GR-54006 Thessaloniki, Greece. RP Duncan, CC (reprint author), NIMH, SCEN, NIH, 5415 W Cedar Lane,Suite 203-B,MSC 2615, Bethesda, MD 20892 USA. EM connieduncan@mail.nih.gov FU Intramural NIH HHS NR 150 TC 30 Z9 33 U1 5 U2 17 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-8760 J9 INT J PSYCHOPHYSIOL JI Int. J. Psychophysiol. PD NOV-DEC PY 2005 VL 58 IS 2-3 BP 133 EP 157 DI 10.1016/j.ijpsycho.2005.05.011 PG 25 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 985MW UT WOS:000233383000006 PM 16203052 ER PT J AU Mirsky, AF Duncan, CC AF Mirsky, AF Duncan, CC TI Pathophysiology of mental illness: A view from the fourth ventricle SO INTERNATIONAL JOURNAL OF PSYCHOPHYSIOLOGY LA English DT Article; Proceedings Paper CT 12th World Congress of Psychophysiology of the International-Organization-of-Psychophysiology CY SEP 18-23, 2004 CL Thessaloniki, GREECE SP Int Org Psychophysiol DE brainstemreticular activating system; fourth ventricle; schizophrenia; absence epilepsy; attention impairment; continuous performance test; neurotransinitters; single neuron analysis; locus coeruleus ID IDIOPATHIC GENERALIZED EPILEPSY; POLYCYSTIC KIDNEY-DISEASE; STEM RETICULAR-FORMATION; CENTRENCEPHALIC EPILEPSY; ORAL-HEALTH; NEUROPSYCHOLOGICAL FINDINGS; PSYCHIATRIC-PATIENTS; SUSTAINED ATTENTION; EVOKED-POTENTIALS; VISUAL-ATTENTION AB The concept of mental disorders as diseases of the brain is as old as the ancient Greek philosopher-physicians. However, for thousands of years, the majority of doctors, as well as laypersons, held strongly to the belief that epilepsy and "madness" (i.e., schizophrenia)-the major disorders discussed in this paper-were caused by demonic "possession." As always, the theory of causation led to apposite therapies: Cast out the devil by whatever means necessary. Later, more enlightened views of etiology led to less punitive "cures," which, to modern sensibilities, still seem barbaric. The 20th century saw the introduction of medications that provide symptomatic relief, if not Cures, for seizure disorders and schizophrenia. In this paper, we consider the etiology of absence (petit mal) epilepsy and schizophrenia based on the pathophysiology underlying the shared symptom of impaired sustained attention. We emphasize the role of abnormal functioning of brainstem structures in the region of the fourth ventricle, whether caused by genetic or environmental factors or a combination thereof Our theorizing relies on the Findings of Lindsley, Magoun, and Moruzzi, who delineated the role of the brainstem reticular activating system in sleep, wakefulness, and consciousness. It also relies on the work of Penfield, Jasper, and Gloor, who sought to illuminate the role of brainstem-thalamus-cortical dysfunction in idiopathic generalized epilepsies. We consider evidence from recent studies that emphasize the phasic attentional functions supported by brainstem structures in the region of the fourth ventricle, and possible genetic links among disorders in which impaired attention is a prominent symptom. Published by Elsevier B.V. C1 NIMH, Sect Clin & Expt Neuropsychol, NIH, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Psychiat, Clin Psychophysiol & Psychopharmacol Lab, Bethesda, MD 20814 USA. RP Mirsky, AF (reprint author), NIMH, Sect Clin & Expt Neuropsychol, NIH, 5415 W Cedar Lane,Suite 203-B,MSC 2615, Bethesda, MD 20892 USA. EM afmirsky@mail.nih.gov FU Intramural NIH HHS NR 91 TC 8 Z9 8 U1 1 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-8760 J9 INT J PSYCHOPHYSIOL JI Int. J. Psychophysiol. PD NOV-DEC PY 2005 VL 58 IS 2-3 BP 162 EP 178 DI 10.1016/j.ijpsycho.2005.06.004 PG 17 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 985MW UT WOS:000233383000008 PM 16213042 ER PT J AU Diner, EK Linehan, M Walther, M AF Diner, EK Linehan, M Walther, M TI Response of papillary renal cell carcinoma in a solitary kidney to high dose interleukin therapy SO INTERNATIONAL JOURNAL OF UROLOGY LA English DT Article DE papillary; kidney neoplasms; interleukin-2; immunotherapy AB Kidney cancer affects 36 000 Americans annually and is responsible for nearly 12 000 deaths every year in the US. Treatment with interleukin-2 (IL-2), the only FDA approved therapy for patients with advanced kidney cancer, is associated with a 10% complete response and a 12% partial response. To date, clear cell renal carcinoma has been the only histological type associated with response to IL-2-based therapy. In the current report, we describe a response to IL-2 therapy in a patient with type I papillary renal carcinoma. C1 NCI, Urol Oncol Branch, CCR, NIH, Bethesda, MD 20892 USA. RP Linehan, M (reprint author), NCI, Urol Oncol Branch, CCR, NIH, Bldg 10,Room 1W-5940,10 Ctr Dr,MSC 1502, Bethesda, MD 20892 USA. EM macw@nih.gov FU Intramural NIH HHS NR 3 TC 5 Z9 5 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0919-8172 J9 INT J UROL JI Int. J. Urol. PD NOV PY 2005 VL 12 IS 11 BP 996 EP 997 DI 10.1111/j.1442-2042.2005.01193.x PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 985WG UT WOS:000233408800011 PM 16351658 ER PT J AU Meleth, AD Agron, E Chan, CC Reed, GF Arora, K Byrnes, G Csaky, KG Ferris, FL Chew, EY AF Meleth, AD Agron, E Chan, CC Reed, GF Arora, K Byrnes, G Csaky, KG Ferris, FL Chew, EY TI Serum inflammatory markers in diabetic retinopathy SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; INTERCELLULAR-ADHESION MOLECULE-1; MONOCYTE CHEMOTACTIC PROTEIN-1; PIGMENT EPITHELIAL-CELLS; BLOOD-RETINA BARRIER; FACTOR-I; PROLIFERATIVE VITREORETINOPATHY; MICROVASCULAR COMPLICATIONS; GENE-EXPRESSION; RANTES AB PURPOSE. To evaluate the association of serum factors with the severity of diabetic retinopathy and to assess their presence in retinal tissue obtained at autopsy. METHODS. The following serum factors of 93 subjects were examined at the National Eye Institute (NEI) clinical center: the chemokines regulated on activation, normal T-cell expressed and presumably secreted ( RANTES)/CCL5, epithelial neutrophil activator (ENA)-78/CXCL5, interferon-induced protein (IP)-10/CXCL10, stromal cell - derived factor (SDF)-1 alpha/CXCLl2, monocyte chemoattractant protein (MCP)-1/CCL2, macrophage inflammatory protein (MIP)-1 alpha/CCL3, interleukin (IL)-8/ CXCL8; the cytokine IL-6; the cell adhesion molecules intercellular adhesion molecule (ICAM-1/CD54) and vascular cell adhesion molecule (VCAM/CD106); and the growth factor vascular endothelial growth factor ( VEGF). Logistic regression was performed to assess the association of these factors with age, sex, severity of retinopathy, hemoglobin A(1C), total cholesterol, creatinine, duration of diabetes, and presence of macular edema. The outcome assessed was severity of retinopathy. Frozen sections of two donor eyes obtained at autopsy from a donor with documented severe nonproliferative diabetic retinopathy and diabetic macular edema and of a normal nondiabetic eye were processed by immunoperoxidase staining with primary antibodies against RANTES, MCP-1, ICAM-1, and LFA-1 alpha/CD11a. RESULTS. The levels of RANTES and SDF-1 alpha were significantly elevated in patients with at least severe nonproliferative diabetic retinopathy compared with those with less severe diabetic retinopathy ( P < 0.001 and 0.007, respectively). Positive immunostaining was observed in the inner retina for MCP-1 and RANTES of the patient with diabetes. Staining was strongly positive throughout the diabetic retina for ICAM-1. Normal retinal tissues showed little reactivity. CONCLUSIONS. Serum chemokines were significantly elevated in patients with at least severe nonproliferative diabetic retinopathy compared with those who had less severe retinopathy. Elevated levels of the chemokines and cell adhesion molecules were also identified in eyes of a donor with ischemic diabetic retinopathy. These findings provide evidence to support the role of inflammation in the pathogenesis of diabetic retinopathy. C1 NEI, Div Epidemiol & Clin Res, NIH, CRC, Bethesda, MD 20892 USA. NEI, Howard Hughes Med Inst, NIH, Bethesda, MD 20892 USA. NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. NEI, Off Sci Director, NIH, Bethesda, MD 20892 USA. Retina Grp Washington, Rockville, MD USA. RP Chew, EY (reprint author), NEI, Div Epidemiol & Clin Res, NIH, CRC, Bldg 10,Room 3-2531,10 Ctr Dr,MSC-1204, Bethesda, MD 20892 USA. EM echew@nei.nih.gov FU Intramural NIH HHS [Z99 EY999999, ZIA EY000414-04] NR 54 TC 130 Z9 152 U1 0 U2 6 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 NOV PY 2005 VL 46 IS 11 BP 4295 EP 4301 DI 10.1167/iovs.04-1057 PG 7 WC Ophthalmology SC Ophthalmology GA 977MH UT WOS:000232807400048 PM 16249511 ER PT J AU Voloboueva, LA Liu, JK Suh, JH Ames, BN Miller, SS AF Voloboueva, LA Liu, JK Suh, JH Ames, BN Miller, SS TI (R)-alpha-lipoic acid protects retinal pigment epithelial cells from oxidative damage SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID ALPHA-LIPOIC ACID; PERFORMANCE LIQUID-CHROMATOGRAPHY; BRAIN MITOCHONDRIAL DECAY; ACETYL-L-CARNITINE; MACULAR DEGENERATION; VITAMIN-E; OLD RATS; METABOLIC ANTIOXIDANT; ION-TRANSPORT; VISION LOSS AB PURPOSE. To determine whether (R)-alpha-lipoic acid ( LA) protects cultured human fetal retinal pigment epithelial (hfRPE) cells against oxidative injury and identify the pathways that may mediate protection. METHODS. Cultured hfRPE cells were pretreated with various concentrations of LA for 14 to 16 hours followed by treatment with a chemical oxidant, tert-butylhydroperoxide (t-BuOOH; 0.8 mM, 3 hours). Reactive oxygen species (ROS) production and cell viability were measured using H2DCF and MTT assays, respectively. RPE cells were evaluated with fluorescent dyes ( SYTOX Orange and SYTO Green; Molecular Probes, Eugene, OR), which differentiate between live and dead cells. Apoptosis was visualized by using the TUNEL assay. Changes in mitochondrial membrane potential were detected by JC-1 dye. Intracellular levels of reduced glutathione (GSH) and oxidized glutathione ( GSSG) were measured by HPLC. Regulation of gamma-glutamylcysteine ligase (GCL), the rate-controlling enzyme of GSH production, was assayed by RT-PCR. RESULTS. Pretreatment of hfRPE cells with LA, 0.2 mM and 0.5 mM, significantly reduced the levels of t-BuOOH-induced intracellular ROS, by 23% and 49%, respectively. LA ( 0.5 mM) prevented oxidant-induced cell death and apoptosis and also increased the viability of oxidant-treated hfRPE cells from 38% to 90% of control. LA upregulated the mRNA expression of GCL, and was protective against t-BuOOH-induced decreases in both mitochondrial membrane potential and intracellular levels of GSH and GSH/GSSG. CONCLUSIONS. The present study suggests that the protective effect of LA involves multiple pathways and that LA could be effective against age-associated increase in oxidative stress and mitochondrial dysfunction in RPE cells. C1 NEI, NIH, Bethesda, MD 20892 USA. Univ Calif Berkeley, Biophys Grad Grp, Berkeley, CA 94720 USA. Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. Childrens Hosp Oakland, Res Inst, Oakland, CA 94609 USA. RP Miller, SS (reprint author), NEI, NIH, 31 Ctr Dr MSC 2510, Bethesda, MD 20892 USA. EM millers@nei.nih.gov FU NCCIH NIH HHS [K05 AT001323-03, K05 AT001323, K05-AT001323]; NEI NIH HHS [EY02205, EY03176, P30 EY003176, R01 EY002205, R21 EY016101, R21 EY016101-01A1, R21 EY016101-02, R37 EY002205]; NIEHS NIH HHS [P30 ES001896, P30-ES01896] NR 74 TC 43 Z9 47 U1 3 U2 10 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 NOV PY 2005 VL 46 IS 11 BP 4302 EP 4310 DI 10.1167/iovs.04-1098 PG 9 WC Ophthalmology SC Ophthalmology GA 977MH UT WOS:000232807400049 PM 16249512 ER PT J AU Fletcher, CV Testa, MA Brundage, RC Chesney, MA Haubrich, R Acosta, EP Martinez, A Jiang, HY Gulick, RM AF Fletcher, CV Testa, MA Brundage, RC Chesney, MA Haubrich, R Acosta, EP Martinez, A Jiang, HY Gulick, RM TI Four measures of antiretroviral medication adherence and virologic response in AIDS clinical trials group study 359 SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE adherence; antiretroviral therapy; pill counts; self-reported adherence; virologic response ID DRUG-RESISTANCE; PROTEASE INHIBITORS; THERAPY; SAQUINAVIR; NELFINAVIR; PREVALENCE; INDINAVIR; RITONAVIR; OUTCOMES; FAILURE AB AIDS Clinical Trials Group (ACTG) 359 was a randomized, partially double-blinded factorial study of 6 antiretroviral regimens, all including saquinavir, among HIV-infected persons in whom prior therapy had failed (n = 258). Counts of remaining saquinavir capsules were determined between weeks 0 and 4; at weeks 4, 8, and 16, self-reported adherence was estimated from 2-day report of doses skipped, therapeutic coverage, and percent of doses taken were determined by electronic monitoring devices applied to saquinavir bottles, and the saquinavir 24-hour area under the curve (AUC) was estimated. Relationships were evaluated among these 4 adherence measures and the primary endpoint of week 16 HIV RNA change. Thirty percent of 254 subjects had HIV RNA : <= 500 copies/mL at week 16. Only self-reported adherence and saquinavir AUC were significantly associated with week 16 HIV RNA change (P = 0.019 and 0.023, respectively), and these measures were higher in subjects with week 16 HIV RNA <= 500 copies/mL (P = 0.03 and 0.008, respectively). The ability to detect a correlation between electronically monitored adherence and virologic response was limited by the small sample size. Self-reported adherence and saquinavir AUC were significant predictors of virologic response, in this evaluation. These findings provide insight into methods of assessing and improving adherence to antiretroviral regimens. C1 Univ Colorado, Hlth Sci Ctr, Dept Clin Pharm, Denver, CO 80262 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Univ Minnesota, Minneapolis, MN USA. NIH, Natl Ctr Complementary & Alternat Med, Rockville, MD USA. Univ Calif San Diego, San Diego, CA 92103 USA. Univ Alabama, Birmingham, AL USA. NIH, Div Aids, Rockville, MD USA. Harvard Univ, Sch Publ Hlth, Stat & Data Anal Ctr, Boston, MA USA. Cornell Univ, Weill Coll Med, New York, NY USA. RP Fletcher, CV (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Clin Pharm, 4200 E 9th Ave,Campus Box C-238, Denver, CO 80262 USA. EM courtney.fletcher@uchsc.edu FU NCRR NIH HHS [RR00070, RR00047]; NIAID NIH HHS [AI32775, AI27666, AI46386, AI51966, K24 AI27670, AI38858, AI38855] NR 21 TC 35 Z9 36 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD NOV 1 PY 2005 VL 40 IS 3 BP 301 EP 306 DI 10.1097/01.qai.0000180078.53321.6a PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 979GF UT WOS:000232929700009 PM 16249704 ER PT J AU Cuthbert, BN AF Cuthbert, BN TI Dimensional models of psychopathology: Research agenda and clinical utility SO JOURNAL OF ABNORMAL PSYCHOLOGY LA English DT Editorial Material DE psychopathology; dimensional approaches; psychiatric diagnosis; internalizing; externalizing ID DSM-V; MOOD DISORDERS; PERSONALITY; DEPRESSION; COMORBIDITY; BEHAVIOR; CORTEX AB This commentary emphasizes the implications for I mental health research agenda that stein from the papers in this special section on dimensional models of psychopathology. These include the need to extend dimensional models to a wider range of psychopathology; the relationship of the dimensions described in these papers, largely based on symptom and self-report measures, to findings from Current research in genetics, neuroimaging, and other domains of neuroscience the need for new scales that can assess the entire range of relevant dimensions with modern psychometric techniques; and ways to employ these dimensions in applied clinical situations. It is concluded that hierarchical dimensional models offer powerful ways of organizing our thinking about psychopathology and will serve to guide many promising avenues of future research. C1 NIMH, Bethesda, MD 20892 USA. RP Cuthbert, BN (reprint author), Univ Minnesota, Dept Psychol, N438C Elliott Hall,75 E River Rd, Minneapolis, MN 55455 USA. EM cuthbert@umn.edu NR 29 TC 33 Z9 33 U1 2 U2 7 PU AMER PSYCHOLOGICAL ASSOC/EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0021-843X J9 J ABNORM PSYCHOL JI J. Abnorm. Psychol. PD NOV PY 2005 VL 114 IS 4 BP 565 EP 569 DI 10.1037/0021-843X.114.4.565 PG 5 WC Psychology, Clinical; Psychology, Multidisciplinary SC Psychology GA 990RK UT WOS:000233760700009 PM 16351380 ER PT J AU Kattan, M Stearns, SC Crain, EF Stout, JW Gergen, PJ Evans, R Visness, CM Gruchalla, RS Morgan, WJ O'Connor, GT Mastin, JP Mitchell, HE AF Kattan, M Stearns, SC Crain, EF Stout, JW Gergen, PJ Evans, R Visness, CM Gruchalla, RS Morgan, WJ O'Connor, GT Mastin, JP Mitchell, HE TI Cost-effectiveness of a home-based environmental intervention for inner-city children with asthma SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE asthma; inner city; cost-effectiveness; asthma intervention; allergen mitigation ID UNITED-STATES; ILLNESS; TRENDS AB Background: Exposure to indoor allergens contributes to increased asthma morbidity. The Inner-City Asthma Study, a randomized trial involving home environmental allergen and irritant remediation among children aged 6 through 11 years with moderate-to-severe asthma, successfully reduced asthma symptoms. A cost-effectiveness analysis can help stakeholders to evaluate the potential costs and benefits of adopting such a program. Objective: We sought to assess the cost-effectiveness of the environmental intervention of the Inner-City Asthma Study. Methods: Incremental cost-effectiveness ratios for a 2-year study period were calculated. Health outcome was measured as symptom-free days. Resource use measures included ambulatory visits, hospitalizations, and pharmaceutical use. CIs were obtained by using bootstrapping. Results: The intervention, which cost $1469 per family, led to statistically significant reductions in symptom days, unscheduled clinic visits, and use of beta-agonist inhalers. Over the year of the intervention and a year of follow-up, the intervention cost was $27.57 per additional symptom-free day (95% CI, $7.46-$67.42). Subgroup analysis showed that targeting the intervention to selected high-risk subgroups did not reduce the incremental cost-effectiveness ratio. Conclusions: A targeted home-based environmental intervention improved health and reduced service use in inner-city children with moderate-to-severe asthma. The intervention is cost-effective when the aim is to reduce asthma symptom days and the associated costs. C1 Mt Sinai Sch Med, Dept Pediat, New York, NY 10029 USA. Univ N Carolina, Dept Hlth Policy & Adm, Chapel Hill, NC USA. Albert Einstein Coll Med, Jacobi Med Ctr, Dept Pediat Emergency Med, Bronx, NY 10467 USA. Univ Washington, Sch Med, Dept Pediat, Seattle, WA 98195 USA. NIAID, Asthma Allergy Inflammat Branch, Div Allergy Immunol Transplantat, NIH, Bethesda, MD 20892 USA. Northwestern Univ, Sch Med, Dept Pediat, Chicago, IL 60611 USA. Northwestern Univ, Sch Med, Dept Med, Chicago, IL 60611 USA. Rho Inc, Chapel Hill, NC USA. Univ Texas, SW Med Ctr Dallas, Dept Med, Dallas, TX 75235 USA. Univ Texas, SW Med Ctr Dallas, Dept Pediat, Dallas, TX 75235 USA. Univ Arizona, Coll Med, Resp Sci Ctr, Tucson, AZ USA. Boston Univ, Sch Med, Boston, MA 02215 USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. RP Kattan, M (reprint author), Mt Sinai Sch Med, Dept Pediat, Box 1202B,1 Gustave L Levy Pl, New York, NY 10029 USA. EM meyer.kattan@mssm.edu OI O'Connor, George/0000-0002-6476-3926 FU NIAID NIH HHS [AI-39761, AI-39769, AI-39776, AI-39785, AI-39789, AI-39900, AI-39901, AI-39902] NR 14 TC 73 Z9 76 U1 1 U2 9 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD NOV PY 2005 VL 116 IS 5 BP 1058 EP 1063 DI 10.1016/j.jaci.2005.07.032 PG 6 WC Allergy; Immunology SC Allergy; Immunology GA 017IG UT WOS:000235686700017 PM 16275376 ER PT J AU Cohen, SG AF Cohen, SG TI Jacques F. A. P. Miller (1931-) SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Biographical-Item C1 NIAID, Hist Med Div, Natl Lib Med, NIH, Bethesda, MD 20892 USA. RP Cohen, SG (reprint author), NIAID, Hist Med Div, Natl Lib Med, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 1 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD NOV PY 2005 VL 116 IS 5 BP 1170 EP 1171 DI 10.1016/j.jaci.2005.03.033 PG 2 WC Allergy; Immunology SC Allergy; Immunology GA 017IG UT WOS:000235686700043 ER PT J AU Depew, MJ Simpson, CA Morasso, M Rubenstein, JLR AF Depew, MJ Simpson, CA Morasso, M Rubenstein, JLR TI Reassessing the Dlx code: the genetic regulation of branchial arch skeletal pattern and development SO JOURNAL OF ANATOMY LA English DT Review DE branchial arch; development; Dlx; genetic; gnathostome; hinge and caps; jaws; pattern; skeleton ID CRANIAL NEURAL CREST; EPITHELIAL-MESENCHYMAL INTERACTIONS; HOMEOBOX GENES; VERTEBRATE HEAD; LIMB DEVELOPMENT; CRANIOFACIAL DEVELOPMENT; MICE LACKING; HOMEOTIC TRANSFORMATION; SIGNALING PATHWAYS; XENOPUS-LAEVIS AB The branchial arches are meristic vertebrate structures, being metameric both between each other within the rostrocaudal series along the ventrocephalic surface of the embryonic head and within each individual arch: thus, just as each branchial arch must acquire a unique identity along the rostrocaudal axis, each structure within the proximodistal axis of an arch must also acquire a unique identity. It is believed that regional specification of metameric structures is controlled by the nested expression of related genes resulting in a regional code, a principal that is though to be demonstrated by the regulation of rostrocaudal axis development in animals exerted by the nested HOM-C/Hox homeobox genes. The nested expression pattern of the Dlx genes within the murine branchial arch ectomesenchyme has more recently led to the proposal of a Dlx code for the regional specification along the proximodistal axis of the branchial arches (i.e. it establishes intra-arch identity). This review re-examines this hypothesis, and presents new work on an allelic series of Dlx loss-of-function mouse mutants that includes various combinations of Dlx1, Dlx2, Dlx3, Dlx5 and Dlx6. Although we confirm fundamental aspects of the hypothesis, we further report a number of novel findings. First, contrary to initial reports, Dlx1, Dlx2 and Dlx1/2 heterozygotes exhibit alterations of branchial arch structures and Dlx2(-/-) and Dlx1/2(-/-) mutants have slight alterations of structures derived from the distal portions of their branchial arches. Second, we present evidence for a role for murine Dlx3 in the development of the branchial arches. Third, analysis of compound Dlx mutants reveals four grades of mandibular arch transformations and that the genetic interactions of cis first-order (e.g. Dlx5 and Dlx6), trans second-order (e.g. Dlx5 and Dlx2) and trans third-order paralogues (e.g. Dlx5 and Dlx1) result in significant and distinct morphological differences in mandibular arch development. We conclude by integrating functions of the Dlx genes within the context of a hypothesized general mechanism for the establishment of pattern and polarity in the first branchial arch of gnathostomes that includes regionally secreted growth factors such as Fgf8 and Bmp and other transcription factors such as Msx1, and is consistent both with the structure of the conserved gnathostome jaw bauplan and the elaboration of this bauplan to meet organismal end-point designs. C1 Guys Hosp, Univ London Kings Coll, Dept Craniofacial Dev, London SE1 9RT, England. NIAMS, Dev Skin Biol Unit, Bethesda, MD USA. Univ Calif San Francisco, Nina Ireland Labs Dev Neurobiol, San Francisco, CA 94143 USA. RP Depew, MJ (reprint author), Guys Hosp, Univ London Kings Coll, Dept Craniofacial Dev, Floors 27-28,London Bridge, London SE1 9RT, England. EM michael.depew@kcl.ac.uk; jlrr@itsa.ucsf.edu FU NIDCD NIH HHS [R01 DC005667]; NIDCR NIH HHS [T32DE07204, T32 DE007204]; NIMH NIH HHS [K05 MH065670] NR 162 TC 161 Z9 168 U1 0 U2 17 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0021-8782 EI 1469-7580 J9 J ANAT JI J. Anat. PD NOV PY 2005 VL 207 IS 5 BP 501 EP 561 PG 61 WC Anatomy & Morphology SC Anatomy & Morphology GA 980EV UT WOS:000232997900007 PM 16313391 ER PT J AU Wakle, MS Joshi, SA Khole, VV AF Wakle, MS Joshi, SA Khole, VV TI Monoclonal antibody from vasectomized mouse identifies a conserved testis-specific antigen TSA70 SO JOURNAL OF ANDROLOGY LA English DT Article DE vasectomy; testicular auto antigen; acrosomal matrix; capacitation ID SPERM PROTEIN SP56; ANTISPERM ANTIBODIES; LEWIS RATS; NEONATAL TOLERIZATION; INFERTILE COUPLES; ACROSOME REACTION; SPERMATOZOA; FERTILIZATION; AUTOANTIBODIES; VASOVASOSTOMY AB Vasectomy results in the occlusion of testicular outflow, leading to autoimmunity characterized by the production of antisperm antibodies (ASA). Reports on the rise in ASA following vasectomy in several species are available; however, not much is known about the specific sperm autoantigens to which postvasectomy antibodies are directed. In the present study, monoclonal antibodies were generated using a vasectomized mouse. One of the monoclonal antibodies, D5E5, identified an approximately 70-kd antigen localized on the principal piece of the tail and also on the tip of the acrosome of mouse sperm. The cognate antigen was expressed postmejotically in a stage-specific manner during spermiogenesis, starting from step 8 of elongating spermatids during spermiogenesis up to mature spermatozoa. The protein was conserved across the species, as observed by its presence in rat, bull, marmoset, and human sperm. Following capacitation, the antigen on the head was seen to shift to the acrosomal region and was lost after the acrosome reaction. However, the localization on tip of the acrosome still persisted, which indicates that the antigen may play a role post-acrosome reaction in sperm egg interaction. Resistance to Triton X-100 solubilization indicates that TSA70 could be an acrosomal matrix protein. In addition, we observed a significant reduction in forward progressive motility of mouse sperm treated in vitro with D5E5. In view of its testis specificity, acrosome and tail localization, and conserved nature, TSA70 is likely to play an important role in sperm function. C1 Natl Inst Res Reprod Hlth, Dept Gamete Immuno Biol, Bombay 400012, Maharashtra, India. NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD USA. RP Khole, VV (reprint author), Natl Inst Res Reprod Hlth, Dept Gamete Immuno Biol, JM St, Bombay 400012, Maharashtra, India. EM vrindakhole@hotmail.com NR 45 TC 5 Z9 5 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 NOV-DEC PY 2005 VL 26 IS 6 BP 761 EP 771 DI 10.2164/jandrol.05045 PG 11 WC Andrology SC Endocrinology & Metabolism GA 974QB UT WOS:000232605400017 PM 16291972 ER PT J AU Groll, AH Mickiene, D Petraitis, V Petraitiene, R Kelaher, A Sarafandi, A Wuerthwein, G Bacher, J Walsh, TJ AF Groll, AH Mickiene, D Petraitis, V Petraitiene, R Kelaher, A Sarafandi, A Wuerthwein, G Bacher, J Walsh, TJ TI Compartmental pharmacokinetics and tissue distribution of the antifungal triazole ravuconazole following intravenous administration of its di-lysine phosphoester prodrug (BMS-379224) in rabbits SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY LA English DT Article; Proceedings Paper CT 42nd Interscience Conference on Antimicrobial Agents and Chemotherapy CY SEP 26-30, 2002 CL SAN DIEGO, CA DE mycoses; chemotherapy; drug development ID IN-VITRO ACTIVITIES; AMPHOTERICIN-B; ORAL TRIAZOLE; CLINICAL-PHARMACOLOGY; EFFICACY; BMS-207147; MODEL; ASPERGILLOSIS; CANDIDIASIS; ER-30346 AB Objectives: Ravuconazole is a broad-spectrum antifungal triazole in clinical development. We investigated the compartmental plasma pharmacokinetics and tissue distribution of ravuconazole following administration of its novel intravenous (iv) di-lysine phosphoester prodrug, BMS-379224. Methods: Normal catheterized rabbits received the prodrug at 1.25, 2.5, 5, 10, 20 and 40 mg/kg once daily as 5 min iv bolus for 8 days. Serial plasma levels were collected at days 1 and 7, and tissues were obtained 30 min after the eighth dose. Concentrations of ravuconazole were determined by a validated HPLC method. Plasma concentration data were fitted to a three-compartment pharmacokinetic model. Pharmacokinetic parameters were estimated by weighted non-linear least squares regression analysis using the WinNonlin computer program. Results: Following single dosing, ravuconazole demonstrated linear plasma pharmacokinetics across the investigated dosage range. C-max, AUC(0-infinity), V-ss, CL and terminal half-life (means +/- SEM) ranged from 2.03 to 58.82 mg/L, 5.80 to 234.21 mg . h/L, 5.16 to 6.43 L/kg, 0.25 to 0.18 L/h/kg and 20.55 to 26.34 h, respectively. Plasma data after multiple dosing revealed non-linear disposition at the 20 and 40 mg/kg dosage levels as evidenced by a dose-dependent decrease in CL (from 0.104-0.147 to 0.030 and 0.022 L/h/kg; P = 0.1053) and an increase in the dose-normalized AUC(0-infinity) (from 2.40-3.01 up to 11.90 and 14.56 mg . h/L; P = 0.0382). Tissue concentrations 30 min after the last dose were highest in the liver (12.91-562.68 mu g/g), adipose tissue (10.57-938.55 mu g/g), lung (5.46-219.12 mu g/g), kidney (3.95-252.44 mu g/g) and brain tissue (2.37-144.85 mu g/g). Conclusions: The pharmacokinetics of ravuconazole fitted best to a three-compartment pharmacokinetic model. The compound revealed non-linear pharmacokinetics at higher dosages, indicating saturable clearance and/or protein binding. Ravuconazole displayed a long elimination half-life and achieved substantial plasma and tissue concentrations including in the brain. C1 NCI, Pediat Oncol Branch, Immunocompromised Host Sect, NIH, Bethesda, MD 20892 USA. Univ Munster, Childrens Hosp, Infect Dis Res Program, Ctr Bone Marrow Transplantat, Munster, Germany. Univ Munster, Childrens Hosp, Dept Pediat Hematol, Munster, Germany. NIH, Surg Serv, Vet Resources Program, Off Res Serv, Bethesda, MD USA. RP Walsh, TJ (reprint author), NCI, Pediat Oncol Branch, Immunocompromised Host Sect, NIH, CRTC-1-575, Bethesda, MD 20892 USA. EM walsht@mail.nih.gov FU Intramural NIH HHS NR 37 TC 11 Z9 13 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-7453 J9 J ANTIMICROB CHEMOTH JI J. Antimicrob. Chemother. PD NOV PY 2005 VL 56 IS 5 BP 899 EP 907 DI 10.1093/jac/dki287 PG 9 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 978VB UT WOS:000232900000017 PM 16172108 ER PT J AU Gray, DE Messer, D Porter, A Ferguson, S Harris, RK Clark, AP Algaier, JW Overstreet, JD Smith, CS AF Gray, DE Messer, D Porter, A Ferguson, S Harris, RK Clark, AP Algaier, JW Overstreet, JD Smith, CS TI Simultaneous quantification of terpenelactones and flavonol aglycones in hydrolyzed Ginkgo biloba extract by liquid chromatography with inline ultraviolet and evaporative light scattering detection SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB We report here a liquid chromatography (LC) method with inline ultraviolet/evaporative light scattering (UV/ELS) detection for the simultaneous quantification of the terpenelactones and flavonol aglycones in a single sample of hydrolyzed Ginkgo biloba extract (GBE). The sample is hydrolyzed by a rapid and convenient oven heating method for 1 h at 90 degrees C with 10% hydrochloric acid. The 1 h hydrolysis was found to be equivalent to the 2.25 h reflux treatment for dry powder extract, where total flavonol glycosides were 28.4 and 28.1%, respectively. Acceptable precision was achieved for total terpenelactones [relative standard deviation (RSD) = 4.8%] by ELS detection, and total flavonol aglycones (RSD = 2.3%) by UV detection. The analytical range was 1.5 to 7.3% (w/w) for the individual terpenelactones (ELS) and 2.5 to 15.0% (w/w) for the individual glycosides (UV) calculated from the aglycones quercetin, kaempferol, and isorhamnetin. This improved method allows for the first time high throughput sample preparation coupled with the quantification of the predominant compounds generally used for quality control of GBE in a single assay. C1 Midwest Res Inst, Kansas City, MO 64110 USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA. RP Gray, DE (reprint author), Midwest Res Inst, 425 Volker Blvd, Kansas City, MO 64110 USA. EM dgray@mriresearch.org FU NIEHS NIH HHS [N01-ES-05457] NR 18 TC 8 Z9 8 U1 0 U2 3 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD NOV-DEC PY 2005 VL 88 IS 6 BP 1613 EP 1620 PG 8 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 990SK UT WOS:000233763300006 PM 16526440 ER PT J AU Shah, JP Phillips, TM Danoff, JV Gerber, LH AF Shah, JP Phillips, TM Danoff, JV Gerber, LH TI An in vivo microanalytical technique for measuring the local biochemical milieu of human skeletal muscle SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE myofascial trigger points; musculoskeletal pain; microdialysis; soft tissue pain; pressure pain threshold ID IMMUNOAFFINITY CAPILLARY-ELECTROPHORESIS; INTRAMUSCULAR INJECTION; ACIDIC SALINE; MICRODIALYSIS; PAIN; HYPERALGESIA; TISSUE AB Myofascial pain associated with myofascial trigger points (MTrPs) is a common cause of nonarticular musculoskeletal pain. Although the presence of MTrPs can be determined by soft tissue palpation, little is known about the mechanisms and biochemical milieu associated with persistent muscle pain. A microanalytical system was developed to measure the in vivo biochemical milieu of muscle in near real time at the subnanogram level of concentration. The system includes a microdialysis needle capable of continuously collecting extremely small samples (similar to 0.5 mu l) of physiological saline after exposure to the internal tissue milieu across a 105-mu m-thick semi-permeable membrane. This membrane is positioned 200 mu m from the tip of the needle and permits solutes of <75 kDa to diffuse across it. Three subjects were selected from each of three groups (total 9 subjects): normal (no neck pain, no MTrP); latent (no neck pain, MTrP present); active (neck pain, MTrP present). The microdialysis needle was inserted in a standardized location in the upper trapezius muscle. Due to the extremely small sample size collected by the microdialysis system, an established microanalytical laboratory, employing immunoaffinity capillary electrophoresis and capillary electrochromatography, performed analysis of selected analytes. Concentrations of protons, bradykinin, calcitonin gene-related peptide, substance P, tumor necrosis factor-alpha, interleukin-1 beta, serotonin, and norepinephrine were found to be significantly higher in the active group than either of the other two groups (P < 0.01). pH was significantly lower in the active group than the other two groups (P < 0.03). In conclusion, the described microanalytical technique enables continuous sampling of extremely small quantities of substances directly from soft tissue, with minimal system perturbation and without harmful effects on subjects. The measured levels of analytes can be used to distinguish clinically distinct groups. C1 NIH, Dept Rehabil Med, Clin Res Ctr, Bethesda, MD 20814 USA. NIH, Ultramicro Anal Immunochem Resource, Div Bioengn & Phys Sci, Off Res Serv, Bethesda, MD 20814 USA. George Washington Univ, Dept Exercise Sci, Washington, DC USA. RP Shah, JP (reprint author), NIH, Dept Rehabil Med, Clin Res Ctr, Bethesda, MD 20814 USA. EM jshah@mail.cc.nih.gov FU Intramural NIH HHS NR 25 TC 259 Z9 263 U1 1 U2 7 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD NOV PY 2005 VL 99 IS 5 BP 1977 EP 1984 DI 10.1152/japplphysiol.00419.2005 PG 8 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 974QZ UT WOS:000232607800046 PM 16037403 ER PT J AU Bordelon, NR Chhabra, R Bucher, JR AF Bordelon, NR Chhabra, R Bucher, JR TI A review of evidence from short-term studies leading to the prediction that diazoaminobenzene (1,3-diphenyltriazine) is a carcinogen SO JOURNAL OF APPLIED TOXICOLOGY LA English DT Review DE micronucleus; electron-spin-resonance; benzene; aniline; urine metabolites; human liver slices; diazoaminobenzene ID BONE-MARROW; ANILINE HYDROCHLORIDE; MICRONUCLEUS TEST; PERIPHERAL-BLOOD; BENZENE; MICE; RATS; METABOLISM; INDUCTION; SALMONELLA AB The National Toxicology Program (NTP) is responsible for providing comprehensive toxicology evaluations of substances, while at the same time incorporating approaches to reduce, refine or replace laboratory animals in routine toxicity/carcinogenicity studies. Consistent with this, a series of metabolism studies in rodents and human liver slices, electron spin resonance spectroscopy (ESR) studies, short-term dermal toxicity studies in rodents, and acute bone marrow micronucleus studies in mice were performed on diazoaminobenzene (DAAB, also known as 1,3-diphenyltriazine). These studies demonstrated that DAAB is metabolized and shares similar genotoxic and toxicological properties to the known human carcinogen, benzene, and the known rodent carcinogen, aniline. These data were used to evaluate the potential carcinogenicity of DAAB without doing a 2-year rodent bioassay. Based on this analysis, DAAB was predicted to be carcinogenic if evaluated in a 2-year rodent bioassay. These data were evaluated to support listing DAAB in the NTP Report on Carcinogens as a substance 'reasonably anticipated to be a human carcinogen'. The purpose of this article is to review the data developed for predicting the carcinogenicity of DAAB. Published in 2005 by John Wiley & Sons, Ltd. C1 NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Bucher, JR (reprint author), NIEHS, Natl Toxicol Program, POB 12233, Res Triangle Pk, NC 27709 USA. EM bucher@niehs.nih.gov NR 44 TC 2 Z9 2 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0260-437X J9 J APPL TOXICOL JI J. Appl. Toxicol. PD NOV-DEC PY 2005 VL 25 IS 6 BP 514 EP 521 DI 10.1002/jat.1087 PG 8 WC Toxicology SC Toxicology GA 984LS UT WOS:000233307000009 PM 16158390 ER PT J AU Pal, D Venkova-Canova, T Srivastava, P Chattoraj, DK AF Pal, D Venkova-Canova, T Srivastava, P Chattoraj, DK TI Multipartite regulation of rctB, the replication initiator gene of Vibrio cholerae chromosome II SO JOURNAL OF BACTERIOLOGY LA English DT Article ID P1 PLASMID REPLICATION; ESCHERICHIA-COLI; DNA-REPLICATION; BACTERIAL PLASMIDS; BAD PROMOTER; PROTEIN; BINDING; ORIGIN; TRANSCRIPTION; CONFORMATION AB Replication initiator proteins in bacteria not only allow DNA replication but also often regulate the rate of replication initiation as well. The regulation is mediated by limiting the synthesis or availability of initiator proteins. The applicability of this principle is demonstrated here for RctB, the replication initiator for the smaller of the two chromosomes of Vibrio cholerae. A strong promoter for the rctB gene named rctBp was identified and found to be autoregulated in Escherichia coli. Promoter activity was lower in V. cholerae than in E. coli, and a part of this reduction is likely to be due to autorepression. Sequences upstream of rctBp, implicated earlier in replication control, enhanced the repression. The action of the upstream sequences required that they be present in cis, implying long-range interactions in the control of the promoter activity. A second gene specific for chromosome II replication, rctA, reduced rctB translation, most likely by antisense RNA control. Finally, optimal rctBp activity was found to be dependent on Dam. Increasing RctB in trans increased the copy number of a miniplasmid carrying oriCII(VC) implying that RctB can be rate limiting for chromosome II replication. The multiple modes of control on RctB are expected to reduce fluctuations in the initiator concentration and thereby help maintain chromosome copy number homeostasis. C1 NCI, Biochem Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Chattoraj, DK (reprint author), NCI, Biochem Lab, Ctr Canc Res, NIH, Bldg 37,Rm 6044, Bethesda, MD 20892 USA. EM chattoraj@nih.gov NR 35 TC 29 Z9 29 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD NOV PY 2005 VL 187 IS 21 BP 7167 EP 7175 DI 10.1128/JB.187.21.7167-7175.2005 PG 9 WC Microbiology SC Microbiology GA 977EV UT WOS:000232786100002 PM 16237000 ER PT J AU Manal, K Chang, CC Hamill, J Stanhope, SJ AF Manal, K Chang, CC Hamill, J Stanhope, SJ TI A three-dimensional data visualization technique for reporting movement pattern deviations SO JOURNAL OF BIOMECHANICS LA English DT Article DE angle-angle plot; color code; joint coupling; parameter-time ID COORDINATION; DYNAMICS; GAIT AB Relative motion plots are the most prevalent method for displaying interjoint coupling. The method, however, is limited when amplitude and timing comparisons of like data are of interest. Another limitation of relative motion plots is that the second parameter (e.g., angle) is included at the expense of a continuous time reference. In this paper, we present a novel method for displaying three-dimensional movement pattern deviations. Parameter-parameter-time data (e.g., knee and hip angle as a function of time) are colorcoded based on the magnitude and direction of the deviation. The color-coded deviations are mapped to an individual's three-dimensional parameter-parameter-time trajectory, resulting in a multi-color, three-dimensional curve depicting how an individual's parameter-parameter-time pattern differs relative to a reference pattern. The algorithmic development of the color-coded parameter-parameter-time display is presented and comparative patient and normative data are reported. (c) 2004 Elsevier Ltd. All rights reserved. C1 Univ Delaware, Biomed Engn Res Ctr, Spencer Lab, Newark, DE 19716 USA. Univ Massachusetts, Amherst, MA 01003 USA. NIH, Phys Disabilities Branch, Bethesda, MD 20892 USA. RP Manal, K (reprint author), Univ Delaware, Biomed Engn Res Ctr, Spencer Lab, 126, Newark, DE 19716 USA. EM manal@udel.edu FU NCRR NIH HHS [RR 16458] NR 12 TC 4 Z9 4 U1 1 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0021-9290 J9 J BIOMECH JI J. Biomech. PD NOV PY 2005 VL 38 IS 11 BP 2151 EP 2156 DI 10.1016/j.jbiomech.2004.10.008 PG 6 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA 972LX UT WOS:000232456400002 PM 16154401 ER PT J AU Collins, MT Lindsay, JR Jain, A Kelly, MH Cutler, CM Weinstein, LS Liu, J Fedarko, NS Winer, KK AF Collins, MT Lindsay, JR Jain, A Kelly, MH Cutler, CM Weinstein, LS Liu, J Fedarko, NS Winer, KK TI Fibroblast growth factor-23 is regulated by l alpha,25-dihydroxyvitamin D SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE fibroblast growth factor-23; fibrous dysplasia; McCune-Albright syndrome; hypoparathyroidism; pseudohypoparathyroidism; phosphate; phosphorus; 1 alpha-hydroxylase; vitamin D; phosphaturia ID FIBROBLAST GROWTH FACTOR-23; DOMINANT HYPOPHOSPHATEMIC RICKETS; VITAMIN-D METABOLISM; FIBROUS DYSPLASIA; PRIMARY HYPERPARATHYROIDISM; ONCOGENIC OSTEOMALACIA; PHOSPHATE HOMEOSTASIS; PARATHYROID-HORMONE; FGF-23; FGF23 AB Introduction: Fibroblast growth factor (FGF)-23 is a recently described hormone that has been shown to be involved in the regulation of phosphate and vitamin D metabolism. The physiologic role of FGF-23 in mineral metabolism and how serum FGF-23 levels are regulated have yet to be elucidated. Three patients with mineral metabolism defects that allowed for the investigation of the regulation of FGF-23 were studied. Materials and Methods: Patient 1 had postsurgical hypoparathyroidism and Munchausen's syndrome and consumed a pharmacologic dose of calcitriol. Patient 2 had postsurgical hypoparathyroidism and fibrous dysplasia of bone. She was treated with increasing doses of calcitriol followed by synthetic PTH(1-34). Patient 3 had pseudohypoparathyroidism type 113 and tertiary hyperparathyroidism. She underwent parathyroidectomy, which was followed by the development of hungry bone syndrome and hypocalcemia, requiring treatment with calcitriol. Serum FGF-23 and serum and urine levels of mineral metabolites were measured in all three patients. Results: Patient 1 had an acute and marked increase in serum FGF-23 (70 to 670 RU/ml; normal range, 18-108 RU/ml) within 24 h in response to high-dose calcitriol administration. Patient 2 showed stepwise increases in serum FGF-23 from 117 to 824 RU/ml in response to increasing serum levels of 1 alpha,25-dihydroxyvitamin D (1,25-D). Finally, before parathyroidectomy, while hypercalcemic, euphosphatemic, with low levels of 1,25-D (10 pg/ml; normal range, 22-67 pg/ml), and with very high serum PTH (863.7 pg/ml; normal range, 6.0-40.0 pg/ml), patient 3 had high serum FGF-23 levels (217 RU/ml). After surgery, while hypocalcemic, euphosphatemic, and with high serum levels of serum 1,25-D (140 pg/ml), FGF-23 levels were higher than preoperative levels (305 RU/ml). It seemed that the phosphaturic effect of FGF-23 was diminished in the absence of PTH or a PTH effect. Conclusions: Serum FGF-23 may be regulated by serum 1,25-D, and its phosphaturic effect may be less in the absence of PTH. C1 Natl Inst Dental & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NIH, Pediat & Reprod Endocrinol Branch, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Johns Hopkins Univ, Dept Med, Div Geriatr Med, Baltimore, MD USA. NIH, Nursing Serv, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NIH, Patient Care Serv, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NIDDKD, Metab Dis Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Johns Hopkins Bayview Med Ctr, Gen Clin Res Ctr, Baltimore, MD USA. Natl Inst Child Hlth, Bethesda, MD USA. NIH, Human Dev Branch, Dept Hlth & Human Serv, Bethesda, MD USA. RP Collins, MT (reprint author), Natl Inst Dental & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM mc247k@nih.gov NR 38 TC 50 Z9 50 U1 0 U2 0 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD NOV PY 2005 VL 20 IS 11 BP 1944 EP 1950 DI 10.1359/JBMR-050718 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 976VO UT WOS:000232761800007 PM 16234967 ER PT J AU Strachan, GD Koike, MA Siman, R Hall, DJ Jordan-Sciutto, KL AF Strachan, GD Koike, MA Siman, R Hall, DJ Jordan-Sciutto, KL TI E2F1 induces cell death, calpain activation, and MDMX degradation in a transcription independent manner implicating a novel role for E2F1 in neuronal loss in SIV encephalitis SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE necrosis; apoptosis; E2F1; SIV; encephalitis; cell cycle; neurodegeneration; calpain; protease; lysosome ID ALZHEIMERS-DISEASE; CATHEPSIN-B; CYCLE REGULATORS; BETA-LAPACHONE; INCREASED EXPRESSION; PARKINSONS-DISEASE; TERMINAL FRAGMENTS; ONCOPROTEIN MDM2; CORTICAL-NEURONS; GROWTH CONTROL AB The E2F1 transcription factor can initiate proliferation or apoptosis, the latter by both transcription-dependent and -independent mechanisms. Recently, an E2F1 mutant lacking the DNA binding domain, E2F1 (180-437), has been implicated in degradation of MDMX and MDM2 proteins via lysosomai proteases. MDM proteins block p53 dependent apoptosis by directly inhibiting p53 stability and function. Here we demonstrate E2F1 (180-437) induces death in HEK293 cells independent of E2F1 transcriptional activation and p53 stabilization. E2F1 (180-437) elevates the activity of the calcium-activated protease, calpain, which is required for E2F1 induced proteolysis of MDMX and E2F1 induced cell loss. To determine if E2F1 could be activating proteolysis via calpains in neurodegeneration, we examined MDMX immunofluorescence in simian immunodeficiency virus encephalitis (SIVE). We found a reciprocal relationship between E2F1 and MDMX staining: in SIVE where E2F1 immunostaining is increased, MDMX is decreased, while in controls where E2F1 immunostaining is low, MDMX is high. Together these experiments support anew function for E2F1 in the activation of calpain proteases and suggest a role for this pathway in SIVE. C1 Univ Penn, Dept Pathol, Sch Dent Med, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Pharmacol, Philadelphia, PA 19104 USA. NIAMS, NIH, Cartilage Biol & Orthopaed Branch, Bethesda, MD USA. RP Jordan-Sciutto, KL (reprint author), Univ Penn, Dept Pathol, Sch Dent Med, 240 S 40th St,Room 312 Levy Res Bldg, Philadelphia, PA 19104 USA. EM Jordan@path.dental.upenn.edu RI Jordan-Sciutto, Kelly/A-1046-2007 NR 63 TC 17 Z9 17 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD NOV 1 PY 2005 VL 96 IS 4 BP 728 EP 740 DI 10.1002/jcb.20574 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 978ES UT WOS:000232857000008 PM 16088944 ER PT J AU De Houwer, A Bornstein, MH Leach, DB AF De Houwer, A Bornstein, MH Leach, DB TI Assessing early communicative ability: a cross-reporter cumulative score for the MacArthur CDI SO JOURNAL OF CHILD LANGUAGE LA English DT Article ID SOCIAL DESIRABILITY; VALIDITY; VOCABULARY; LANGUAGE; SCALE; FORM AB Thirty middle- to upper middle-class monolingual Dutch speaking families consisting of at least a mother and a father completed the Infant Form 'Words and Gestures' of the Dutch adaptation of the MacArthur Communicative Development Inventory for the same child at I; I. Considerable inter- and intrafamily variation emerged in how two (or three) different reporters who are all presumably close to the child assess a particular child's communicative abilities. The greater the child's communicative ability, as rated by any one reporter, the more differences tended to emerge between reporters. In order to take into account multiple reporters' assessments of the same child, we propose the use of a Cumulative CDI Score that credits the child with the best score for any item on the CDI as checked by any single reporter. We conclude that single reporter CDI reports may underestimate the child's communicative knowledge. C1 Univ Antwerp, Dept Commun Sci, B-2610 Antwerp, Belgium. NICHHD, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. RP De Houwer, A (reprint author), Univ Antwerp, Dept Commun Sci, Campus 3 Eiken,Univ Pl 1, B-2610 Antwerp, Belgium. EM annick.dehouwer@ua.ac.be RI Putnick, Diane/B-1707-2009; OI Putnick, Diane/0000-0002-6323-749X FU NIMHD NIH HHS [263-MD-005126, 263-MD-104775] NR 23 TC 28 Z9 28 U1 1 U2 11 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0305-0009 J9 J CHILD LANG JI J. Child Lang. PD NOV PY 2005 VL 32 IS 4 BP 735 EP 758 DI 10.1017/S0305000905007026 PG 24 WC Psychology, Developmental; Linguistics; Psychology, Experimental SC Psychology; Linguistics GA 007HR UT WOS:000234960100002 PM 16429709 ER PT J AU Fox, CS Yang, Q Cupples, LA Guo, CY Atwood, LD Murabito, JM Levy, D Mendelsohn, ME Housman, DE Shearman, AM AF Fox, CS Yang, Q Cupples, LA Guo, CY Atwood, LD Murabito, JM Levy, D Mendelsohn, ME Housman, DE Shearman, AM TI Sex-specific association between estrogen receptor-alpha gene variation and measures of adiposity: The Framingham Heart Study SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID BODY-MASS INDEX; DISEASE RISK-FACTORS; CARDIOVASCULAR-DISEASE; FAT DISTRIBUTION; US ADULTS; LINKAGE; OBESITY; WOMEN; POLYMORPHISMS; POPULATION AB Background: Polymorphisms in estrogen receptor-alpha( ESR1) may be associated with variation in body mass index and waist circumference. However, most prior studies have been limited by sample size and power. Methods: DNA from 1763 unrelated men and women ( mean age, 56 yr) from the Framingham Heart Study offspring cohort was genotyped for four ESR1 polymorphisms: T30C ( rs2077647) in exon 1, PvuII ( rs2234693), and XbaI ( rs 9340799) in intron 1, and C1335G ( rs 1801132) in exon 4. Results: Men homozygous for the PvuII C allele ( frequency, 0.45) had lower waist circumference ( 99.3 cm), compared with TT homozygous men ( 99.8 cm) and heterozygotes ( 100.6 cm) ( P < 0.004). Similar results were obtained with XbaI, which lies in the same linkage disequilibrium block. C1335G also demonstrated a gender- specific association: men with CG or GG genotypes had lower mean body mass index, 27.7 and 27.9 kg/m(2), respectively, compared with 28.6 kg/m(2) among the CC homozygotes ( P < 0.01). No significant associations were seen with T30C, nor were associations observed among women. Conclusions: Polymorphisms in ESR1 are associated with measures of adiposity in men. These associations further support the hypothesis that the intron 1 region of ESR1 influences phenotypes important for cardiovascular risk. C1 NHLBI, Heart Study, Framingham, MA 01702 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Boston Univ, Sch Med, Gen Internal Med Sect, Boston, MA 02118 USA. MIT, Canc Res Ctr, Cambridge, MA 02139 USA. Tufts Univ, New England Med Ctr, Dept Med, Mol Cardiol Res Inst, Boston, MA 02111 USA. Tufts Univ, New England Med Ctr Specialized Ctr Res Ischem He, Boston, MA 02111 USA. NHLBI, NIH, Bethesda, MD 20892 USA. RP Fox, CS (reprint author), 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM foxca@nhlbi.nih.gov RI Yang, Qiong/G-5438-2014; OI Cupples, L. Adrienne/0000-0003-0273-7965; Murabito, Joanne/0000-0002-0192-7516 FU NHLBI NIH HHS [N01-HC-25195] NR 31 TC 45 Z9 47 U1 0 U2 3 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD NOV PY 2005 VL 90 IS 11 BP 6257 EP 6262 DI 10.1210/jc.2005-0670 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 981VI UT WOS:000233115700049 PM 16144952 ER PT J AU Diehr, P Johnson, LL Patrick, DL Psaty, B AF Diehr, P Johnson, LL Patrick, DL Psaty, B TI Methods for incorporating death into health-related variables in longitudinal studies SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE death; longitudinal; years of healthy life; ADL; quality of life; stroke ID SELF-RATED HEALTH; QUALITY-OF-LIFE; OLDER-ADULTS; MORTALITY; SF-36; TIME AB Background and Objectives: Longitudinal studies of health over time may be misleading if some people die. Self-rated health (excellent to poor) and the SF-36 profile scores have been transformed to incorporate death. We applied the same approaches to incorporate death into activities of daily living difficulties (ADLs), IADLs, mini-mental state examination, depressive symptoms, blocks walked per week, bed days, the timed walk, body mass index and blood pressure. Study Design and Setting: The Cardiovascular Health Study of 5,888 older adults, was followed up to 9 years. Mean age was 73 at baseline, and 658 had an incident stroke during follow-up. Methods: We recoded each variable as the probability of being healthy I year in the future (PHF), conditional oil the Current value of the variable. This was done for 11 health variables, using three definitions of healthy, and two estimation models. Deaths were set to zero, and mean PHF was plotted in the 3 years before and after an incident stroke. Results: Analyses without the deaths were too optimistic. The effect of stroke was greatest oil hospitalization, self-rated health, and IADLs. Alternative transformation approaches had slightly different results. Conclusion: These methods provide an additional approach for handling death in longitudinal studies. (c) 2005 Elsevier Inc. All rights reserved. C1 Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Univ Washington, Dept Hlth Sci, Seattle, WA 98195 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. NCCAM, Off Clin & Regulatory Affairs, NIH, Bethesda, MD 20892 USA. RP Diehr, P (reprint author), Univ Washington, Dept Biostat, Box 357232, Seattle, WA 98195 USA. EM pdichr@u.washington.edu FU NHLBI NIH HHS [N01 HC-15103, N01-HC-85079, N01-HC-35129, N01-HC-85086] NR 18 TC 20 Z9 20 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD NOV PY 2005 VL 58 IS 11 BP 1115 EP 1124 DI 10.1016/j.clinepi.2005.05.002 PG 10 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 981MA UT WOS:000233091500007 PM 16223654 ER PT J AU Guo, LY Hu-Li, J Paul, WE AF Guo, LY Hu-Li, J Paul, WE TI Probabilistic regulation of IL-4 production SO JOURNAL OF CLINICAL IMMUNOLOGY LA English DT Article DE cytokines; chromatin; monoallelism; green florescence protein ID LOCUS-CONTROL REGION; STIMULATORY FACTOR-I; TH2 CYTOKINE LOCUS; T-CELL-CLONES; ASYNCHRONOUS REPLICATION; MONOALLELIC EXPRESSION; COORDINATE REGULATOR; V(D)J RECOMBINATION; GENE; ALLELES AB Among a population of uniformly differentiated TH2 cells, only a portion express IL-4 upon stimulation and those that do often express the product of only a single allele. We review the evidence for the basis of IL-4 monoallelism and argue that it depends upon probabilistic expression of the Il4 gene. Further, we argue that probabilistic expression may provide a powerful mechanism through which certain key functions of IL-4, such as immunoglobulin class switching and determination of macrophage phenotype, may be efficiently regulated. C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Paul, WE (reprint author), NIAID, Immunol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM wpaul@niaid.nih.gov FU Intramural NIH HHS NR 33 TC 9 Z9 10 U1 0 U2 0 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0271-9142 J9 J CLIN IMMUNOL JI J. Clin. Immunol. PD NOV PY 2005 VL 25 IS 6 BP 573 EP 581 DI 10.1007/s10875-005-8218-5 PG 9 WC Immunology SC Immunology GA 997UH UT WOS:000234273800007 PM 16380820 ER PT J AU Fichtner-Feigl, S Fuss, IJ Preiss, JC Strober, W Kitani, A AF Fichtner-Feigl, S Fuss, IJ Preiss, JC Strober, W Kitani, A TI Treatment of murine Th1-and Th2-mediated inflammatory bowel disease with NF-kappa B decoy oligonucleotides SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article AB The Th1 and Th2 T cell responses that underlie inflammatory bowel diseases (IBDs) are likely to depend on NF-kappa B transcriptional activity. We explored this possibility in studies in which we determined the capacity of NF-kappa B decoy oligodeoxynucleotides (decoy ODNs) to treat various murine models of IBD. In initial studies, we showed that i.r. (intrarectal) or i.p. administration of decoy ODNs encapsulated in a viral envelope prevented and treated a model of acute trinitrobenzene sulfonic acid-induced (TNBS-induced) colitis, as assessed by clinical course and effect on Th1 cytokine production. In further studies, we showed that NF-kappa B decoy ODNs were also an effective treatment of a model of chronic TNBS-colitis, inhibiting both the production of IL-23/IL-17 and the development of fibrosis that characterizes this model. Treatment of TNBS-induced inflammation by i.r. administration of NF-kappa B decoy ODNs did not inhibit NF-kappa B in extraintestinal organs and resulted in CD4(+) T cell apoptosis, suggesting that such treatment is highly focused and durable. Finally, we showed that NF-kappa B decoy ODNs also prevented and treated oxazolone-colitis and thus affect a Th2-mediated inflammatory process. In each case, decoy administration led to inflammation-clearing effects, suggesting a therapeutic potency applicable to human IBD. OF C1 NIAID, Mucosal Immun Sect, Host Def Lab, NIH, Bethesda, MD 20892 USA. RP Fichtner-Feigl, S (reprint author), NIAID, Mucosal Immun Sect, Host Def Lab, NIH, Bldg 10 Clin Res Ctr 5W-3864,10 Ctr Dr, Bethesda, MD 20892 USA. EM stefan.fichtner@klinik.uni-regensburg.de FU Intramural NIH HHS NR 67 TC 117 Z9 130 U1 0 U2 7 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD NOV PY 2005 VL 115 IS 11 BP 3057 EP 3071 DI 10.1172/JCI24792 PG 15 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 980MH UT WOS:000233022100016 PM 16239967 ER PT J AU Chen, M Gavrilova, O Zhao, WQ Nguyen, A Lorenzo, J Shen, L Nackers, L Pack, S Jou, W Weinstein, LS AF Chen, M Gavrilova, O Zhao, WQ Nguyen, A Lorenzo, J Shen, L Nackers, L Pack, S Jou, W Weinstein, LS TI Increased glucose tolerance and reduced adiposity in the absence of fasting hypoglycemia in mice with liver-specific G(s)alpha deficiency SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID GLUCOSE-6-PHOSPHATASE CATALYTIC SUBUNIT; FORKHEAD TRANSCRIPTION FACTOR; INCREASED INSULIN SENSITIVITY; DEPENDENT DIABETES-MELLITUS; G(S)ALPHA KNOCKOUT MICE; ALPHA-CELL HYPERPLASIA; GLUCAGON RECEPTOR; HEPATIC GLUCONEOGENESIS; COACTIVATOR PGC-1; GENE-TRANSCRIPTION AB The G protein G(s)alpha is essential for hormone-stimulated cAMP generation and is an important metabolic regulator. We investigated the role of liver G(s)-signaling pathways by developing mice with liver-specific G,a deficiency (LGsKO mice). LGsKO mice had increased liver weight and glycogen content and reduced adiposity, whereas survival, body weight, food intake, and metabolic rates at ambient temperature were unaffected. LGsKO mice had increased glucose tolerance with both increased glucose-stimulated insulin secretion and increased insulin sensitivity in liver and muscle. Fed LGsKO mice were hypoglycemic and hypoinsulinemic, with low expression of hepatic gluconeogenic enzymes and PPAR gamma coactivator-1. However, LGsKO mice maintained normal fasting glucose and insulin levels, probably due to prolonged breakdown of glycogen stores and possibly increased extrahepatic gluconeogenesis. Lipid metabolism was unaffected in fed LGsKO mice, but fasted LGsKO mice had increased lipogenic and reduced lipid oxidation gene expression in liver and increased serum triglyceride and FFA levels. LGsKO mice had very high serum glucagon and glucagon-like peptide-1 levels and pancreatic a cell hyperplasia, probably secondary to hepatic glucagon resistance and/or chronic hypoglycemia. Our results define novel roles for hepatic G(s)-signaling pathways in glucose and lipid regulation, which may prove useful in designing new therapeutic targets for diabetes and obesity. C1 NIDDK, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. NIDDK, MOuse Metab Core Lab, NIH, Bethesda, MD 20892 USA. Blanchette Rockefeller Neurosci Inst, Rockville, MD USA. RP Weinstein, LS (reprint author), NIDDK, Metab Dis Branch, NIH, Bldg 10,Room 8C101, Bethesda, MD 20892 USA. EM leew@amb.niddk.nih.gov FU Intramural NIH HHS NR 45 TC 71 Z9 73 U1 0 U2 1 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD NOV PY 2005 VL 115 IS 11 BP 3217 EP 3227 DI 10.1172/JCI24196 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 980MH UT WOS:000233022100031 PM 16239968 ER PT J AU Chun, TW Nickle, DC Justement, JS Large, D Semerjian, A Curlin, ME O'Shea, MA Hallahan, CW Daucher, M Ward, DJ Moir, S Mullins, JI Kovacs, C Fauci, AS AF Chun, TW Nickle, DC Justement, JS Large, D Semerjian, A Curlin, ME O'Shea, MA Hallahan, CW Daucher, M Ward, DJ Moir, S Mullins, JI Kovacs, C Fauci, AS TI HIV-infected individuals receiving effective antiviral therapy for extended periods of time continually replenish their viral reservoir SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article AB The persistence of latently infected, resting CD4(+) T cells is considered to be a major obstacle in preventing the eradication of HIV-1 even in patients who have received effective antiviral therapy for an average duration of 5 years. Although previous studies have suggested that the latent HIV reservoir in the resting CD4+ T cell compartment is virologically quiescent in the absence of activating stimuli, evidence has been mounting to suggest that low levels of ongoing viral replication persist and in turn, prolong the overall half-life of HIV in patients receiving antiviral therapy. Here, we demonstrate the persistence of replication-competent virus in CD4(+)T cells in a cohort of patients who had received uninterrupted antiviral therapy for up to 9.1 years that rendered them consistently aviremic throughout that time. Surprisingly, substantially higher levels of HIV proviral DNA were found in activated CD4(+)T cells when compared with resting CD4(+)T cells in the majority of patients we studied. Phylogenetic analyses revealed evidence for cross infection between the resting and activated CD4(+)T cell compartments, suggesting that ongoing reactivation of latently infected, resting CD4(+)T cells and spread of virus by activated CD4(+)T cells may occur in these patients. Such events may allow continual replenishment of the CD4(+)T cell reservoir and resetting of the half-life of the latently infected, resting CD4(+)T cells despite prolonged periods of aviremia. C1 NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. Univ Washington, Dept Microbiol, Seattle, WA 98195 USA. NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA. Dupont Circle Phys Grp, Washington, DC USA. Univ Toronto, Dept Med, Toronto, ON, Canada. RP Chun, TW (reprint author), NIAID, Immunoregulat Lab, NIH, Bldg 10,Room 6A32,9000 Rockville Pike, Bethesda, MD 20892 USA. EM twchun@nih.gov FU Intramural NIH HHS NR 36 TC 164 Z9 169 U1 0 U2 2 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD NOV PY 2005 VL 115 IS 11 BP 3250 EP 3255 DI 10.1172/JCI26197 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 980MH UT WOS:000233022100034 PM 16276421 ER PT J AU Beignon, AS McKenna, K Skoberne, M Manches, O DaSilva, I Kavanagh, DG Larsson, M Gorelick, RJ Lifson, JD Bhardwaj, N AF Beignon, AS McKenna, K Skoberne, M Manches, O DaSilva, I Kavanagh, DG Larsson, M Gorelick, RJ Lifson, JD Bhardwaj, N TI Endocytosis of HIV-1 activates plasmacytoid dendritic cells via toll-like receptor-viral RNA interactions SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; INTERFERON-PRODUCING CELLS; HERPES-SIMPLEX-VIRUS; HEPATITIS-C VIRUS; IFN-ALPHA; INFECTED INDIVIDUALS; ADAPTIVE IMMUNITY; CPG-DNA; T-CELLS; CHEMOKINE RECEPTORS AB HIV-1 directly activates human plasmacytoid DCs (pDCs) by upregulating the expression of costimulatory and MHC molecules and maturation markers, increasing T cell stimulatory activity, and inducing the production of type I interferons and TNF-alpha. A consequence of this activation is the bystander maturation of myeloid DCs and overall enhancement of antigen-presenting function. However, little is known about the mechanism(s) of pDC activation by HIV-1. Here we demonstrate by in vitro studies that IFN-alpha production by pDC in response to HIV-1 requires at least 2 interactions between the cell and virus. Initially, envelope-CD4 interactions mediate endocytosis of HIV-1, as demonstrated through the use of inhibitors of binding, fusion, endocytosis, and endosomal acidification. Subsequently, endosomally delivered viral nucleic acids, particularly RNA, stimulate pDCs through TLRs, as activation is reproduced with purified genomic RNA but not viral RNA packaging-deficient HIV-1 and blocked with different inhibitory TLR ligands. Finally, by using genetic complementation, we show that TLR7 is the likely primary target. Viral RNA rather than DNA in early retrotranscripts appears to be the active factor in HIV-1 that induces IFN-alpha secretion by pDCs. Since the decline in pDCs in chronic HIV-1 infection is associated with high viral loads and opportunistic infections, exploiting this natural adjuvant activity of HIV-1 RNA might be useful in the development of vaccines for the prevention of AIDS. C1 NYU, Sch Med, New York, NY 10016 USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NCI, AIDS Vaccine Program, Sci Applicat Int Corp, Frederick Inc, Frederick, MD 21701 USA. RP Bhardwaj, N (reprint author), NYU, Sch Med, 550 1St Ave,MSB 507, New York, NY 10016 USA. EM bhardn02@popmail.med.nyu.edu OI BEIGNON, Anne-Sophie/0000-0003-0863-983X FU NCI NIH HHS [N01-CO-124000, CA84512, P01 CA084512]; NIAID NIH HHS [AI44628, AI55274, F32 AI058457, R01 AI044628, R21 AI055274, R37 AI044628]; Wellcome Trust NR 83 TC 394 Z9 416 U1 4 U2 16 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD NOV PY 2005 VL 115 IS 11 BP 3265 EP 3275 DI 10.1172/JCI26032 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 980MH UT WOS:000233022100036 PM 16224540 ER PT J AU Bodaghi, S Wood, LV Roby, G Ryder, C Steinberg, SM Zheng, ZM AF Bodaghi, S Wood, LV Roby, G Ryder, C Steinberg, SM Zheng, ZM TI Could human papillomaviruses be spread through blood? SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID CERVICAL INTRAEPITHELIAL NEOPLASIA; HUMAN-IMMUNODEFICIENCY-VIRUS; POLYMERASE-CHAIN-REACTION; SQUAMOUS-CELL CARCINOMAS; PERIPHERAL-BLOOD; CANCER PATIENTS; MESSENGER-RNA; HPV DNA; INFECTION; TYPE-16 AB The human papillomaviruses (HPVs) are epitheliotropic viruses that require the environment of a differentiating squamous epithelium for their life cycle. HPV infection through abrasion of the skin or sexual intercourse causes benign warts and sometimes cancer. HPV DNA detected in the blood has been interpreted as having originated from metastasized cancer cells. The present study examined HPV DNA in banked, frozen peripheral blood mononuclear cells (PBMCs) from 57 U.S. human immunodeficiency virus (HIV)-infected pediatric patients collected between 1987 and 1996 and in fresh PBMCs from 19 healthy blood donors collected in 2002 to 2003. Eight patients and three blood donors were positive mostly for two subgroups of the HPV type 16 genome. The HPV genome detected in all 11 PBMC samples existed as an episomal form, albeit at a low DNA copy number. Among the eight patients, seven acquired HIV from transfusion (three associated with hemophilia) and one acquired HIV through vertical transmission; this patient also had received a transfusion before sampling. Our data suggest that PBMCs may be HPV carriers and might spread the virus through blood. C1 NCI, HIV & AIDS Malignancy Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Zheng, ZM (reprint author), NCI, HIV & AIDS Malignancy Branch, Canc Res Ctr, NIH, 10 Ctr Dr,Rm 10 S255,MSC-1868, Bethesda, MD 20892 USA. EM zhengt@exchange.nih.gov FU Intramural NIH HHS; NCI NIH HHS [Z01 SC010357-06] NR 47 TC 43 Z9 45 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD NOV PY 2005 VL 43 IS 11 BP 5428 EP 5434 DI 10.1128/JCM.43.11.5428-5434.2005 PG 7 WC Microbiology SC Microbiology GA 984NS UT WOS:000233312200003 PM 16272465 ER PT J AU Nissley, DV Halvas, EK Hoppman, NL Garfinkel, DJ Mellors, JW Strathern, JN AF Nissley, DV Halvas, EK Hoppman, NL Garfinkel, DJ Mellors, JW Strathern, JN TI Sensitive phenotypic detection of minor drug-resistant human immunodeficiency virus type 1 reverse transcriptase variants SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID IN-VIVO; ESCHERICHIA-COLI; PLASMA SAMPLES; SUBTYPE-A; HIV-1; INHIBITORS; PROTEASE; ASSAY; MUTATIONS; SUSCEPTIBILITY AB Detection of drug-resistant variants is important for the clinical management of human immunodeficiency virus type 1 (HIV-1) infection and for studies on the evolution of drug resistance. Here we show that hybrid elements composed of the Saccharomyces cerevisiae retrotransposon Ty1 and the reverse transcriptase (RT) of HIV-1 are useful tools for detecting, monitoring, and isolating drug-resistant reverse transcriptases. This sensitive phenotypic assay is able to detect nonnucleoside reverse transcriptase inhibitor-resistant RT domains derived from mixtures of infectious molecular clones of HIV-1 in plasma and from clinical samples when the variants comprise as little as 0.3 to 1% of the virus population. Our assay can characterize the activities and drug susceptibilities of both known and novel reverse transcriptase variants and should prove useful in studies of the evolution and clinical significance of minor drug-resistant viral variants. C1 SAIC Frederick Inc, NCI, Basic Res Program, Ft Detrick, MD 21702 USA. Univ Pittsburgh, Sch Med, Div Infect Dis, Pittsburgh, PA USA. NCI, Gene Regulat & Chromosome Biol Lab, Frederick, MD 21701 USA. RP Nissley, DV (reprint author), SAIC Frederick Inc, NCI, Basic Res Program, POB B, Ft Detrick, MD 21702 USA. EM nissley@ncifcrf.gov FU NCI NIH HHS [N01CO12400, N01-CO-12400] NR 38 TC 10 Z9 12 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD NOV PY 2005 VL 43 IS 11 BP 5696 EP 5704 DI 10.1128/JCM.43.11.5696-5704.2005 PG 9 WC Microbiology SC Microbiology GA 984NS UT WOS:000233312200045 PM 16272507 ER PT J AU Corby, PM Lyons-Weiler, J Bretz, WA Hart, TC Aas, JA Boumenna, T Goss, J Corby, AL Junior, HM Weyant, RJ Paster, BJ AF Corby, PM Lyons-Weiler, J Bretz, WA Hart, TC Aas, JA Boumenna, T Goss, J Corby, AL Junior, HM Weyant, RJ Paster, BJ TI Microbial risk indicators of early childhood caries SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID MOLECULAR ANALYSIS; DECAY AB The aim of this study was to use molecular identification methods, such as 16S RNA gene sequence and reverse-capture checkerboard hybridization, for identification of the bacteria associated with dental caries and with dental health in a subset of 204 twins aged 1.5 to 7 years old. A total of 448 plaque samples (118 collected from caries-free subjects and 330 from caries-active subjects) were used for analysis. We compared the bacteria found in biofilms of children exhibiting severe dental caries, with different degrees of lesion severity, with those found in biofilms of caries-free children. A panel of 82 bacterial species was selected, and a PCR-based reverse-capture checkerboard method was used for detection. A simple univariate test was used to determine the overabundance and underabundance of bacterial species in the diseased and in the healthy groups. Features identified with this univariate test were used to construct a probabilistic disease prediction model. Furthermore, a method for the analysis of global patterns of gene expression was performed to permit simultaneous analysis of the abundance of significant species by allowing cross-bacterial comparisons of abundance profiles between caries-active and caries-free subjects. Our results suggested that global patterns of microbial abundance in this population are very distinctive. The top bacterial species found to be over-abundant in the caries-active group were Actinomyces sp. strain B 19SC, Streptococcus mutans, and Lactobacillus spp., which exhibited an inverse relationship to beneficial bacterial species, such as Streptococcus parasanguinis, Abiotrophia defectiva, Streptococcus mitis, Streptococcus oralis, and Streptococcus sanguinis. C1 Univ Pittsburgh, Sch Dent Med, Div Pediat & Dev Dent Sci, Pittsburgh, PA 15261 USA. Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. Univ Pittsburgh, Hillman Canc Ctr, Pittsburgh, PA USA. Natl Inst Dent & Craniofacial Res, Div Intramural Clin Res, NIH, Bethesda, MD USA. Forsyth Inst, Boston, MA USA. Univ Oslo, Inst Oral Biol, Oslo, Norway. Twins Inst Genet Res, Montes Claros, Brazil. UNIMONTES, Montes Claros, Brazil. RP Corby, PM (reprint author), Univ Pittsburgh, Sch Dent Med, Div Pediat & Dev Dent Sci, 3501 Terrace St,Room 386, Pittsburgh, PA 15261 USA. EM pcorby@pitt.edu RI Aas, Jorn /A-3805-2008 FU NIDCR NIH HHS [R01 DE015351, DE15351, DE14528, K12 DE014528] NR 13 TC 93 Z9 106 U1 3 U2 16 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD NOV PY 2005 VL 43 IS 11 BP 5753 EP 5759 DI 10.1128/JCM.43.11.5753-5759.2005 PG 7 WC Microbiology SC Microbiology GA 984NS UT WOS:000233312200051 PM 16272513 ER PT J AU Sparreboom, A Baker, SD Verweij, J AF Sparreboom, A Baker, SD Verweij, J TI Paclitaxel repackaged in an albumin-stabilized nanoparticle: Handy or just a dandy? SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID FORMULATION VEHICLES; BOUND PACLITAXEL; CREMOPHOR-FREE; BREAST-CANCER; TAXOL; PHARMACOKINETICS; ABI-007; METABOLISM; RESISTANCE C1 NCI, Bethesda, MD 20892 USA. Erasmus Univ, Ctr Med, Dr Daniel Den Hoed Canc Ctr, Dept Med Oncol, Rotterdam, Netherlands. Sidney Kimmel Comprehens Canc Ctr John Hopkins, Baltimore, MD USA. RP Sparreboom, A (reprint author), NCI, Bethesda, MD 20892 USA. RI Sparreboom, Alex/B-3247-2008 NR 24 TC 16 Z9 17 U1 0 U2 8 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 NOV 1 PY 2005 VL 23 IS 31 BP 7765 EP 7767 DI 10.1200/JCO.2005.03.7135 PG 3 WC Oncology SC Oncology GA 981DE UT WOS:000233066700001 PM 16258080 ER PT J AU Tan-Chiu, E Yothers, G Romond, E Geyer, CE Ewer, M Keefe, D Shannon, RP Swain, SM Brown, A Fehrenbacher, L Vogel, VG Seay, TE Rastogi, P Mamounas, EP Wolmark, N Bryant, J AF Tan-Chiu, E Yothers, G Romond, E Geyer, CE Ewer, M Keefe, D Shannon, RP Swain, SM Brown, A Fehrenbacher, L Vogel, VG Seay, TE Rastogi, P Mamounas, EP Wolmark, N Bryant, J TI Assessment of cardiac dysfunction in a randomized trial comparing doxorubicin and cyclophosphamide followed by paclitaxel, with or without trastuzumab as adjuvant therapy in node-positive, human epidermal growth factor receptor 2-overexpressing breast cancer: NSABP B-31 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 26th Annual San Antonio Breast Cancer Symposium CY DEC 03-06, 2003 CL SAN ANTONIO, TX AB Purpose Trastuzumab is effective in treating human epidermal growth factor receptor 2 (HER2)-positive breast cancer, but it increases frequency of cardiac dysfunction (CID) when used with or after anthracyclines. Patients and Methods National Surgical Adjuvant Breast and Bowel Project trial B-31 compared doxorubicin and cyclophosphamide (AC) followed by paclitaxel with AC followed by paclitaxel plus 52 weeks of trastuzumab beginning concurrently with paclitaxel in patients with node-positive, HER2-positive breast cancer. Initiation of trastuzumab required normal post-AC left ventricular ejection fraction (LVEF) on multiple-gated acquisition scan. If symptoms suggestive of congestive heart failure (CHF) developed, source documents were blindly reviewed by an independent panel of cardiologists to determine whether criteria were met for a cardiac event (CE), which was defined as New York Heart Association class III or IV CHF or possible/probable cardiac death. Frequencies of CEs were compared between arms. Results Among patients with normal post-AC LVEF who began post-AC treatment, five of 814 control patients subsequently had confirmed CEs (four CHFs and one cardiac death) compared with 31 of 850 trastuzumab-treated patients (31 CHFs and no cardiac deaths). The difference in cumulative incidence at 3 years was 3.3% (4.1% for trastuzumab-treated patients minus 0.8% for control patients-, 95% CI, 1.7% to 4.9%). Twenty-seven of the 31 patients in the trastuzumab arm have been followed for ! 6 months after diagnosis of a CE; 26 were asymptomatic at last assessment, and 18 remained on cardiac medication. CHFs were more frequent in older patients and patients with marginal post-AC LVEF. Fourteen percent of patients discontinued trastuzumab because of asymptomatic decreases in LVEF; 4% discontinued trastuzumab because of symptomatic cardiotoxicity. Conclusion Administering trastuzumab with paclitaxel after AC increases incidence of CHF and lesser CID. Potential cardiotoxicity should be carefully considered when discussing benefits and risks of this therapy. C1 Allegheny Canc Ctr, Pittsburgh, PA 15212 USA. Univ Pittsburgh, NSABP, NSABP Biostat Ctr, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Inst Canc, Breast Canc Inst, Pittsburgh, PA 15260 USA. Magee Womens Hosp, Pittsburgh, PA 15213 USA. Canc Res Network Inc, Plantation, FL USA. Univ Kentucky, Markey Canc Ctr, Lexington, KY 40506 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Novartis Pharmaceut Corp, E Hanover, NJ USA. NCI, Canc Therapeut Branch, Bethesda, MD 20892 USA. Kaiser Permanente, Vallejo, CA USA. Atlanta Canc Care, Atlanta, GA USA. Aultman Hosp, Canton, OH USA. RP Geyer, CE (reprint author), Allegheny Canc Ctr, 5th Floor,320 N Ave, Pittsburgh, PA 15212 USA. EM cgeyer@wpahs.org FU NCI NIH HHS [U10-CA-12027, U10-CA-69651] NR 12 TC 432 Z9 447 U1 0 U2 13 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 NOV 1 PY 2005 VL 23 IS 31 BP 7811 EP 7819 DI 10.1200/JCO.2005.02.4091 PG 9 WC Oncology SC Oncology GA 981DE UT WOS:000233066700011 PM 16258083 ER PT J AU Jatoi, I Anderson, WF Rao, SR Devesa, SS AF Jatoi, I Anderson, WF Rao, SR Devesa, SS TI Breast cancer trends among black and white women in the United States SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID RANDOMIZED-TRIALS; MORTALITY; RATES; CHEMOTHERAPY; MAMMOGRAPHY; DISPARITIES; TAMOXIFEN; ETHNICITY; SURVIVAL; OUTCOMES AB Purpose Overall US breast cancer mortality rates are higher among black women than white women, and the disparity is widening. To investigate this disparity, we examined incidence data and changes in mortality trends according to age, year of death (calendar period), and date of birth (birth cohort). Calendar period mortality trends reflect the effects of new medical interventions, whereas birth cohort mortality trends reflect alterations in risk factors. Patients and Methods Incidence data were obtained from the Connecticut and National Cancer Institute Surveillance, Epidemiology, and End Results registries and mortality data were obtained from the National Center for Health Statistics. Changes in age, period, and cohort mortality trends were analyzed with Poisson regression. Results For both races, breast cancer incidence rates for localized and regional disease diverged in the late 1970s. Almost concurrently, overall mortality rates diverged among blacks and whites. For both races, mortality increases with age, but blacks have higher mortality at age younger than 57. The calendar period curves revealed declining mortality for whites over the entire study period. For blacks, calendar period mortality declined until the late 1970s, and then sharply increased. After 1994, calendar period mortality declined for both. For women born between 1872 and 1950, trends in mortality were similar for blacks and whites. For women born after 1950, mortality decreased more rapidly for blacks. Conclusion The widening racial disparity in breast cancer mortality seems attributable to calendar period rather than birth cohort effects. Thus, differences in response or access to newer medical interventions may largely account for these trends. C1 Uniformed Serv Univ Hlth Sci, Dept Surg, Div Canc Epidemiol & Genet, NCI,NIH,Dept Hlth & Human Serv, Bethesda, MD 20814 USA. USN, Ctr Med, Bethesda, MD 20814 USA. RP Jatoi, I (reprint author), Uniformed Serv Univ Hlth Sci, Dept Surg, Div Canc Epidemiol & Genet, NCI,NIH,Dept Hlth & Human Serv, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM ismail.jatoi@us.army.mil NR 33 TC 73 Z9 75 U1 0 U2 4 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 NOV 1 PY 2005 VL 23 IS 31 BP 7836 EP 7841 DI 10.1200/JCO.2004.01.0421 PG 6 WC Oncology SC Oncology GA 981DE UT WOS:000233066700014 PM 16258086 ER PT J AU Karlin, JD Nguyen, D Yang, SX Lipkowitz, S AF Karlin, JD Nguyen, D Yang, SX Lipkowitz, S TI Epidermal growth factor receptor expression in breast cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter ID ERBB-2 C1 Canc Res Ctr, Cellular & Mol Biol Lab, Bethesda, MD USA. NCI, Canc Therapeut Branch, NIH, Bethesda, MD 20892 USA. RP Karlin, JD (reprint author), Canc Res Ctr, Cellular & Mol Biol Lab, Bethesda, MD USA. NR 3 TC 6 Z9 6 U1 0 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 NOV 1 PY 2005 VL 23 IS 31 BP 8118 EP 8119 DI 10.1200/JCO.2005.03.0130 PG 2 WC Oncology SC Oncology GA 981DE UT WOS:000233066700051 PM 16258112 ER PT J AU Berman, DM Wincovitch, S Garfield, S Romeo, MJ AF Berman, DM Wincovitch, S Garfield, S Romeo, MJ TI Grading melanocytic dysplasia in paraffin wax embedded tissue by the nucleic acid index SO JOURNAL OF CLINICAL PATHOLOGY LA English DT Article ID CUTANEOUS MALIGNANT-MELANOMA; ACRIDINE-ORANGE; BRAF MUTATIONS; RNA-CONTENT; LESIONS; NEVI; BENIGN; DNA; DISCRIMINATION; MICROSCOPY AB Background: Although nucleic acid derangements are the hallmark of melanocytic dysplasia, the gold standard for its diagnosis remains the microscopic evaluation of haematoxylin and eosin stained slides. However, light microscopy is subjective and crucial genomic changes do not always show as changes in histology. Aims: To introduce the nucleic acid index (NAI) as a means of analysing nucleic acid derangements in histological sections at the level of the individual cell and within the context of its microenvironment. Methods: Confocal laser scanning microscopy was performed on melanocytic lesions stained with acridine orange (AO), a fluorescent stain for DNA and RNA. The NAI, calculated by measuring the fluorescence intensities of AO in nuclei relative to the surrounding cytoplasm, reflects the concentration of DNA relative to RNA. Results: When applied to benign naevi, dysplastic naevi, and melanoma, a very strong significant association was seen between lower NAI and malignant potential (p < 0.0001). Strong inverse correlations were found between NAI and both mitotic index and Breslow thickness. Interestingly, the NAI for dysplastic naevi is between that of melanoma and most benign naevi, consistent with their intermediate biological behaviour and histological appearance. Conclusion: By providing a quantitative measure for melanocytic neoplasia, the NAI may improve the diagnosis of melanocytic lesions and the selection of treatment. C1 NCI, Pathol Lab, Bethesda, MD 20896 USA. NCI, Expt Carcinogenesis Lab, Bethesda, MD 20892 USA. RP Berman, DM (reprint author), Bristol Myers Squibb Co, Princeton, NJ 08543 USA. EM david.berman@bms.com NR 30 TC 3 Z9 3 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0021-9746 J9 J CLIN PATHOL JI J. Clin. Pathol. PD NOV PY 2005 VL 58 IS 11 BP 1206 EP 1210 DI 10.1136/jcp.2005.026559 PG 5 WC Pathology SC Pathology GA 978RF UT WOS:000232890000017 PM 16254113 ER PT J AU Grant, BF Hasin, DS Blanco, C Stinson, FS Chou, P Goldstein, RB Dawson, DA Smith, S Saha, TD Huang, B AF Grant, BF Hasin, DS Blanco, C Stinson, FS Chou, P Goldstein, RB Dawson, DA Smith, S Saha, TD Huang, B TI The epidemiology of social anxiety disorder in the United States: Results from the national epidemiologic survey on alcohol and related conditions SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Review ID AVOIDANT PERSONALITY-DISORDER; DSM-IV DISORDERS; COMORBIDITY SURVEY REPLICATION; DIAGNOSTIC INTERVIEW SCHEDULE; GENERAL-POPULATION SAMPLE; MENTAL-HEALTH; PSYCHIATRIC-DISORDERS; LIFETIME PREVALENCE; PHOBIA SUBTYPES; CLINICAL INTERVIEWERS AB Objective: To present nationally representative data on 12-month and lifetime prevalence, correlates and comorbidity of social anxiety disorder (SAD) among adults in the United States as determined by the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions. Design: Face-to-face survey. Setting: The United States. Participants: Adults (aged 18 and over) residing in households and group quarters (N = 43,093). Main Outcome Measures: Prevalence and associations of SAD with sociodemographic and psychiatric correlates and Axis I and 11 disorders. Results: The prevalence of 12-month and lifetime DSM-IV SAD was 2.8% (95% CI = 2.5 to 3.1) and 5.0% (95% Cl = 4.6 to 5.4), respectively. Being Native American, being young, or having low income increased risk, while being male, being of Asian, Hispanic, or black race/ethnicity, or living in urban or more populated regions reduced risk. Mean age at onset of SAD was 15.1 years, with a mean duration of 16.3 years. Over 80% of individuals with SAD received no treatment, and the mean age at first treatment was 27.2 years. Current and lifetime SAD were significantly related to other specific psychiatric disorders, most notably generalized anxiety, bipolar 1, and avoidant and dependent personality disorders. The mean number of feared social situations among individuals with SAD was 7.0, with the majority reporting anxiety in performance situations. Conclusions: Social anxiety disorder was associated with substantial unremitting course and extremely early age at onset. Social anxiety disorder often goes untreated, underscoring the need for health care initiatives geared toward increasing recognition and treatment. Comprehensive evaluation of patients with SAD should include a systematic assessment of comorbid disorders, and novel approaches to the treatment of comorbid SAD are needed. C1 NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, Dept Hlth & Human Serv,NIH, Bethesda, MD 90034 USA. Columbia Univ, Dept Epidemiol, New York, NY USA. Columbia Univ, Dept Psychiat, New York, NY USA. New York State Psychiat Inst & Hosp, New York, NY 10032 USA. RP Grant, BF (reprint author), NIAAA, Div Intramural Clin & Biol Res, Lab Epidemiol & Biol Res, NIH, MS 9304,5635 Fishers Lane, Bethesda, MD 20892 USA. EM bgrant@willco.niaaa.nih.gov RI Blanco, Carlos/I-4906-2013; OI Blanco, Carlos/0000-0001-6187-3057; Goldstein, Rise/0000-0002-9603-9473 FU NIAAA NIH HHS [K05 AA 014221]; NIDA NIH HHS [K23 DA 00482, R01 DA 018652, R03 DA 015559] NR 114 TC 264 Z9 266 U1 8 U2 41 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD NOV PY 2005 VL 66 IS 11 BP 1351 EP 1361 PG 11 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 988VI UT WOS:000233628800002 PM 16420070 ER PT J AU Burg, G Kempf, W Cozzio, A Feit, J Willemze, R Jaffe, ES Dummer, R Berti, E Cerroni, L Chimenti, S Diaz-Perez, JL Grange, F Harris, NL Kazakov, DV Kerl, H Kurrer, M Knobler, R Meijer, CJLM Pimpinelli, N Ralfkiaer, E Russell-Jones, R Sander, C Santucci, M Sterry, W Swerdlow, SH Vermeer, MH Wechsler, J Whittaker, S AF Burg, G Kempf, W Cozzio, A Feit, J Willemze, R Jaffe, ES Dummer, R Berti, E Cerroni, L Chimenti, S Diaz-Perez, JL Grange, F Harris, NL Kazakov, DV Kerl, H Kurrer, M Knobler, R Meijer, CJLM Pimpinelli, N Ralfkiaer, E Russell-Jones, R Sander, C Santucci, M Sterry, W Swerdlow, SH Vermeer, MH Wechsler, J Whittaker, S TI WHO/EORTC classification of cutaneous lymphomas 2005: histological and molecular aspects SO JOURNAL OF CUTANEOUS PATHOLOGY LA English DT Review ID T-CELL LYMPHOMA; GRANULOMATOUS-SLACK-SKIN; WORINGER-KOLOPP-DISEASE; OF-THE-LITERATURE; FOLLICULAR MYCOSIS-FUNGOIDES; BCL-2 PROTEIN EXPRESSION; HEAVY-CHAIN GENE; SEZARY-SYNDROME; INTRAVASCULAR LYMPHOMATOSIS; PAGETOID RETICULOSIS AB The new WHO/EORTC classification for cutaneous lymphomas comprises mature T-cell and natural killer (NK)-cell neoplasms, mature B-cell neoplasms, and immature hematopoietic malignancies. It reflects the unique features of lymphoproliferative diseases of the skin, and at the same time it is as compatible as possible with the concepts underlying the WHO classification for nodal lymphomas and the EORTC classification of cutaneous lymphomas. This article reviews the histological, phenotypical, and molecular genetic features of the various nosological entities included in this new classification. These findings always have to be interpreted in the context of the clinical features and biologic behavior. Aim: To review the histological, phenotypical and molecular genetic features of the various nosological entities of the new WHO/EORTC classification for cutaneous lymphomas. Methods: Extensive review of the literature cited in Medline and own data of the authors. Results: The WHO/EORTC classification of cutaneous lymphomas comprises mature T-cell and NK-cell neoplasms, mature B-cell neoplasms and immature hematopoietic malignancies. It reflects the unique features of primary cutaneous lymphoproliferative diseases. Conclusion: This classification is as much as possible compatible with the concept of the WHO classification for nodal lymphomas and the EORTC classification of cutaneous lymphomas. The histological, phenotypical and molecular genetic features always have to be interpreted in the context of the clinical features and biologic behavior. C1 Univ Zurich Hosp, Dept Dermatol, CH-8091 Zurich, Switzerland. Histol Diagnost, Kemp & Pfaltz, Zurich, Switzerland. Univ Hosp Brno, Dept Pathol, Brno, Czech Republic. Leiden Univ, Med Ctr, Netherlands Lab Pathol, Dept Dermatol, Leiden, Netherlands. NCI, NIH, Bethesda, MD 20892 USA. Univ Milan, Dept Dermatol, Milan, Italy. Graz Univ, Dept Dermatol, Graz, Austria. Univ Rome, Dept Dermatol, Rome, Italy. Cruces Hosp, Dept Dermatol, Bilbao, Spain. Univ Reims, Dept Dermatol, Reims, France. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Charles Univ, Med Fac Hosp, Sikls Dept Pathol, Plzen, Czech Republic. Univ Zurich Hosp, Dept Pathol, CH-8091 Zurich, Switzerland. Univ Vienna, Dept Dermatol, Vienna, Austria. Vrije Univ Amsterdam, Med Ctr, Dept Pathol, Amsterdam, Netherlands. Univ Florence, Dept Dermatol Sci, Florence, Italy. Univ Copenhagen, Dept Pathol, Copenhagen, Denmark. St Thomas Hosp, St Johns Inst Dermatol, Skin Tumour Unit, London, England. Allgemeines Krankenhaus St Georg, Dept Dermatol, Hamburg, Germany. Univ Florence, Dept Human Pathol & Oncol, Florence, Italy. Humboldt Univ, Charite, Dept Dermatol, Berlin, Germany. Univ Pittsburgh, Sch Med, Dept Pathol, Div Hematopathol, Pittsburgh, PA USA. Hop Henri Mondor, Dept Pathol, F-94010 Creteil, France. RP Burg, G (reprint author), Univ Zurich Hosp, Dept Dermatol, Gloriastr 31, CH-8091 Zurich, Switzerland. EM g.burg@usz.ch RI Berti, Emilio/F-5256-2012 NR 212 TC 165 Z9 176 U1 1 U2 6 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0303-6987 J9 J CUTAN PATHOL JI J. Cutan. Pathol. PD NOV PY 2005 VL 32 IS 10 BP 647 EP 674 DI 10.1111/j.0303-6987.2005.00495.x PG 28 WC Dermatology; Pathology SC Dermatology; Pathology GA 984OQ UT WOS:000233314600001 PM 16293178 ER PT J AU Chang, J Zhang, C Tani-Ishii, N Shi, S Wang, CY AF Chang, J Zhang, C Tani-Ishii, N Shi, S Wang, CY TI NF-kappa B activation in human dental pulp stem cells by TNF and LPS SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE NF-kappa B; dental pulp stem cells; tumor necrosis factor; LPS; inflammation ID PORPHYROMONAS-GINGIVALIS LIPOPOLYSACCHARIDE; GENE-EXPRESSION; INDUCED APOPTOSIS; PHOSPHORYLATION; INHIBITION; INDUCTION; PROFILES; THERAPY; DEATH AB Post-natal human dental pulp stem cells (DPSCs) represent a unique precursor population in the dental pulp, which has multipotential and can regenerate a dentin/pulp-like structure. Because the dental pulp is frequently infected by oral bacteria due to dental decay, in this study, we examined whether lipopolysaccharide (LPS) and tumor necrosis factor (TNF) activated the immunologic transcription factor nuclear factor kappa B (NF-kappa B) in DPSCs. We found that both TNF and LPS activated the I-kappa B kinase complex (IKK) in DPSCs to induce the phosphorylation and degradation Of I kappa B alpha, resulting in the nuclear translocation of NF-kappa B. Consistently, both TNF and LPS rapidly induced the expression of the NF-kappa B-dependent gene interteukin-8 (IL-8). However, unlike in monocytes, we found that LPS could not induce the phosphorylation of the NF-kappa B active subunit p65 in DPSCs. In summary, our studies suggest that DPSCs may be involved in immune responses during pulpal infection through activating NF-kappa B. C1 Univ Michigan, Lab Mol Signaling & Apoptosis, Dept Biol & Mat Sci, Sch Dent, Ann Arbor, MI 48109 USA. Kanagawa Dent Coll, Div Operat Dent & Endodont, Dept Oral Med, Kanagawa, Japan. Peking Univ, Hlth Sci Ctr, Sch Stomatol, Beijing 100871, Peoples R China. Natl Inst Dent & Craniofacial Res, Sect Oral Biol, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD USA. RP Wang, CY (reprint author), Univ Michigan, Lab Mol Signaling & Apoptosis, Dept Biol & Mat Sci, Sch Dent, 1011 N Univ Ave, Ann Arbor, MI 48109 USA. EM cunywang@umich.edu FU NIDCR NIH HHS [R01 DE 01593, R01 DE 016513, R01 DE015973, R01 DE016513] NR 28 TC 50 Z9 56 U1 1 U2 11 PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD NOV PY 2005 VL 84 IS 11 BP 994 EP 998 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 977KA UT WOS:000232801100005 PM 16246929 ER PT J AU Ozdemir, D Hart, PS Ryu, OH Choi, SJ Ozdemir-Karatas, M Firatli, E Piesco, N Hart, TC AF Ozdemir, D Hart, PS Ryu, OH Choi, SJ Ozdemir-Karatas, M Firatli, E Piesco, N Hart, TC TI MMP20 active-site mutation in hypomaturation Amelogenesis Imperfecta SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE amelogenesis imperfecta; MMP20; proteolytic activity; hypomaturation; enamelysin ID ENAMEL; NOMENCLATURE; PHENOTYPE; MMP-20; IDENTIFICATION; CLASSIFICATION; PROTEINASES; GENOTYPE AB The Amelogenesis Imperfecta (AI) are a group of clinically and genetically heterogeneous disorders that affect enamel formation. To date, mutations in 4 genes have been reported in various types of AI. Mutations in the genes encoding the 2 enamel proteases, matrix metalloproteinase 20 (MMP20) and kallikrein 4 (KLK4), have each been reported in a single family segregating autosomal-recessive hypomaturation AI. To determine the frequency of mutations in these genes, we analyzed 15 Turkish probands with autosomal-recessive hypomaturation AI for MMP20 and KLK4 gene mutations. No KLK4 mutations were found. A novel MMP20 mutation (g.16250T > A) was found in one family. This missense mutation changed the conserved active-site His226 residue of the zinc catalytic domain to Gln (p.H226Q). Zymogram analysis demonstrated that this missense mutation abolished MMP20 proteolytic activity. No MMP20 mutations were found in the remaining 14 probands, underscoring the genetic heterogeneity of hypomaturation AI. C1 NIDCR, NIH, Bethesda, MD 20892 USA. NHGRI, NIH, Bethesda, MD 20892 USA. Istanbul Univ, Sch Dent, Istanbul, Turkey. Univ Pittsburgh, Sch Dent Med, Pittsburgh, PA 15261 USA. RP Hart, TC (reprint author), NIDCR, NIH, 10 Ctr Dr,Bldg 10,Room 5-2531, Bethesda, MD 20892 USA. EM thart@mail.nih.gov RI FIRATLI, Erhan/E-4241-2013; OI FIRATLI, Erhan/0000-0002-4154-6929; Ozdemir-Karatas, Meltem/0000-0001-7132-9936 FU Intramural NIH HHS; NIDCR NIH HHS [T35 DE007336-01] NR 24 TC 79 Z9 83 U1 0 U2 5 PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD NOV PY 2005 VL 84 IS 11 BP 1031 EP 1035 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 977KA UT WOS:000232801100012 PM 16246936 ER PT J AU Ozdemir, D Hart, PS Firatli, E Aren, G Ryu, OH Hart, TC AF Ozdemir, D Hart, PS Firatli, E Aren, G Ryu, OH Hart, TC TI Phenotype of ENAM mutations is dosage-dependent SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE amelogenesis imperfecta; enamel; enamel pitting; gene dosage; enamelin ID DOMINANT AMELOGENESIS IMPERFECTA; NOMENCLATURE; CLASSIFICATION; GENOTYPE; DEFECTS AB Five mutations in the ENAM gene have been found to cause hypoplastic amelogenesis imperfecta (AI), with phenotypes ranging from localized enamel pitting in carriers to severe hypoplastic AI. To determine the generality of ENAM mutations in hypoplastic AI, we sequenced the ENAM gene in ten Turkish families segregating autosomal hypoplastic AI. In two families, ENAM mutations were found. A novel nonsense mutation (g.12663C > A; p.S246X) was identified in one family segregating local hypoplastic AI as a dominant trait. Affected individuals in a second family segregating autosomal-recessive AI were compound heterozygotes for a novel insertion mutation (g.12946_12947insAGTCAGTACCAGTACTGT GTC) and a previously described insertion (g.13185_13186insAG) mutation. Heterozygous carriers of either insertion had a localized enamel-pitting phenotype. These findings substantiate that enamel phenotypes of ENAM mutations may be dose-dependent, with generalized hypoplastic AI segregating as a recessive trait and localized enamel pitting segregating as a dominant trait. C1 NHGRI, Off Clin Director, NIH, Bethesda, MD 20892 USA. NIDCR, Clin Res Core, NIH, Bethesda, MD USA. Istanbul Univ, Sch Dent, Dept Pedodont, Istanbul, Turkey. Istanbul Univ, Sch Dent, Dept Periodontol, Istanbul, Turkey. NIDCR, Sect Craniofacial & Dent Genet, NIH, Bethesda, MD USA. RP Hart, PS (reprint author), NHGRI, Off Clin Director, NIH, Bldg 10 CRC 3-2551,10 Ctr Dr, Bethesda, MD 20892 USA. EM shart@mail.nih.gov RI FIRATLI, Erhan/E-4241-2013 OI FIRATLI, Erhan/0000-0002-4154-6929 FU Intramural NIH HHS; NIDCR NIH HHS [DE 12879, R01 DE012879] NR 24 TC 48 Z9 51 U1 0 U2 2 PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD NOV PY 2005 VL 84 IS 11 BP 1036 EP 1041 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 977KA UT WOS:000232801100013 PM 16246937 ER PT J AU Bretz, WA Corby, PM Schork, NJ Robinson, MT Coelho, M Costa, S Melo, MR Weyant, RJ Hart, TC AF Bretz, WA Corby, PM Schork, NJ Robinson, MT Coelho, M Costa, S Melo, MR Weyant, RJ Hart, TC TI Longitudinal analysis of heritability for dental caries traits SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE genetics; dental caries; epidemiology; twins; longitudinal ID CARIOUS DENTIN; CHILDREN; MATRIX; PHENOTYPE; INVITRO; ENAMEL AB The role of genetic and environmental factors on dental caries progression in young children was determined. A detailed caries assessment was performed in 2 examinations on 314 pairs of twins initially 1.5 to 8 years old. Surface-based caries prevalence rates (SBCPR) and lesion severity (LSI) were computed. Heritability estimates were calculated by SOLAR software. Analyses were performed on all ages combined and by age group (1.5 <= 4; 4-6; > 6). Overall heritability estimates (H) of net increments SBCPRs were H = 30.0 (p < 0.0001), and were greatest for the youngest (H = 30.0) and oldest groups (H = 46.3). Overall LSI heritability estimates [H = 36.1 (p < 0.0001)] were also greatest for the youngest (H = 51.2) and oldest groups (H = 50.6). Similar findings were found for net increments of occlusal surfaces and deep dentinal lesions SBCPRs (H = 46.4-56.2). These findings are consistent with a significant genetic contribution to dental caries progression and severity in both emerging primary and permanent dentitions. C1 Univ Pittsburgh, Sch Dent Med, Div Pediat & Dev Dent Sci, Pittsburgh, PA 15261 USA. Univ Calif San Diego, Sch Med, San Diego, CA 92103 USA. Univ Estadual Montes Claros, Montes Claros, Brazil. Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. RP Bretz, WA (reprint author), Univ Pittsburgh, Sch Dent Med, Div Pediat & Dev Dent Sci, 3501 Terrace St,Room 380, Pittsburgh, PA 15261 USA. EM wab2@pitt.edu FU NIDCR NIH HHS [DE 14528, R01 DE015351, DE 15351, K12 DE014528] NR 21 TC 51 Z9 53 U1 1 U2 12 PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD NOV PY 2005 VL 84 IS 11 BP 1047 EP 1051 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 977KA UT WOS:000232801100015 PM 16246939 ER PT J AU Nguyen, RHN Wilcox, AJ AF Nguyen, RHN Wilcox, AJ TI Terms in reproductive and perinatal epidemiology: I. Reproductive terms SO JOURNAL OF EPIDEMIOLOGY AND COMMUNITY HEALTH LA English DT Editorial Material ID ASSISTED CONCEPTION; HIV-INFECTION; PREGNANCY; SUBFERTILITY; ABC; TRANSITION; MENOPAUSE; OVULATION; ESTROGEN; WOMEN C1 NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. RP Nguyen, RHN (reprint author), NIEHS, Epidemiol Branch, 111 TW Alexander Dr,POB 12233,Mail Drop A3-05, Res Triangle Pk, NC 27709 USA. EM nguyen5@niehs.nih.gov OI Wilcox, Allen/0000-0002-3376-1311 FU Intramural NIH HHS NR 27 TC 10 Z9 10 U1 0 U2 2 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0143-005X J9 J EPIDEMIOL COMMUN H JI J. Epidemiol. Community Health PD NOV PY 2005 VL 59 IS 11 BP 916 EP 919 DI 10.1136/jech.2004.023457 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 975HO UT WOS:000232651800003 PM 16234416 ER PT J AU Elischberger, HB AF Elischberger, HB TI The effects of prior knowledge on children's memory and suggestibility SO JOURNAL OF EXPERIMENTAL CHILD PSYCHOLOGY LA English DT Article DE knowledge; memory; suggestibility; stereotype ID FALSE CHILDHOOD MEMORIES; EVENT MEMORY; INDIVIDUAL-DIFFERENCES; REPEATED EXPERIENCE; TRACE STRENGTH; INFORMATION; RECALL; MISINFORMATION; REPRESENTATION; COMPREHENSION AB In this study, 5- and 6-year-olds were read a story and asked to recall its details. Two independent factors-prestory knowledge and poststory suggestions-were crossed to examine the effects on children's story recall. The results indicated that prestory social knowledge about the story protagonist as well as academic knowledge relating to the content of the story influenced the accuracy of children's recall immediately after the story presentation. Following the suggestive interview, children reported interviewer-provided social and academic misinformation to a greater extent when the misinformation was consistent with their prior knowledge. In contrast, children were more likely to refute misinformation that contradicted their academic knowledge. These findings are discussed in terms of the mechanisms underlying the knowledge-memory and knowledge-suggestibility linkages. Published by Elsevier Inc. C1 Natl Inst Child Hlth & Human Dev, Sect Social & Emot Dev, Bethesda, MD 20892 USA. Univ N Carolina, Dept Psychol, Chapel Hill, NC 27599 USA. RP Elischberger, HB (reprint author), Albion Coll, Dept Psychol, Olin Hall,611 E Porter St, Albion, MI 49224 USA. EM HElischberger@albion.edu NR 78 TC 15 Z9 16 U1 7 U2 12 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-0965 J9 J EXP CHILD PSYCHOL JI J. Exp. Child Psychol. PD NOV PY 2005 VL 92 IS 3 BP 247 EP 275 DI 10.1016/j.jecp.2005.05.002 PG 29 WC Psychology, Developmental; Psychology, Experimental SC Psychology GA 982EU UT WOS:000233141500003 PM 16040045 ER PT J AU Curwin, BD Hein, MJ Sanderson, WT Barr, DB Heederik, D Reynolds, SJ Ward, EM Alavanja, MC AF Curwin, BD Hein, MJ Sanderson, WT Barr, DB Heederik, D Reynolds, SJ Ward, EM Alavanja, MC TI Urinary and hand wipe pesticide levels among farmers and nonfarmers in Iowa SO JOURNAL OF EXPOSURE ANALYSIS AND ENVIRONMENTAL EPIDEMIOLOGY LA English DT Article DE pesticides; exposure; biomonitoring; urine; hand wipe; herbicides; insecticides; farmer ID AGRICULTURAL HEALTH; ATRAZINE EXPOSURE; APPLICATORS; CANCER; INSECTICIDES; METABOLITES; BIOMARKERS; MALATHION AB In the spring and summer of 2001, as part of a larger study investigating farm family pesticide exposure and home contamination in Iowa, urine and hand wipe samples were collected from 24 male farmers and 23 male nonfarmer controls. On two occasions approximately 1 month apart, one hand wipe sample and an evening and morning urine sample were collected from each participant. The samples were analyzed for the parent compound or metabolites of six commonly used agricultural pesticides: alachlor, atrazine, acetochlor, metolachlor, 2,4-dichlorophenoxyacetic acid (2,4- D) and chlorpyrifos. For atrazine, acetochlor, metolachlor and 2,4- D, farmers who reported applying the pesticide had significantly higher urinary metabolite levels than nonfarmers, farmers who did not apply the pesticide, and farmers who had the pesticide commercially applied (P- value < 0.05). Generally, there were no differences in urinary pesticide metabolite levels between nonfarmers, farmers who did not apply the pesticide, and farmers who had the pesticide commercially applied. Among farmers who reported applying 2,4- D themselves, time since application, amount of pesticide applied, and the number of acres to which the pesticide was applied were marginally associated with 2,4- D urine levels. Among farmers who reported applying atrazine themselves, time since application and farm size were marginally associated with atrazine mercapturate urine levels. Farmers who reported using a closed cab to apply these pesticides had higher urinary pesticide metabolite levels, although the difference was not statistically significant. Farmers who reported using closed cabs tended to use more pesticides. The majority of the hand wipe samples were nondetectable. However, detection of atrazine in the hand wipes was significantly associated with urinary levels of atrazine above the median (P- value < 0.01). C1 NIOSH, Div Surveillance Hazard Evaluat & Field Studies, Cincinnati, OH 45226 USA. Univ Iowa, Dept Occupat & Environm Med, Iowa City, IA USA. Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA 30341 USA. Univ Utrecht, Inst Risk Assessment Sci, NL-3508 TC Utrecht, Netherlands. Colorado State Univ, Dept Environm & Radiol Hlth Sci, Ft Collins, CO 80523 USA. Amer Canc Soc, Dept Epidemiol & Surveillance Res, Atlanta, GA 30329 USA. Natl Canc Inst, Bethesda, MD USA. RP Curwin, BD (reprint author), NIOSH, Div Surveillance Hazard Evaluat & Field Studies, 4676 Columbia Pkwy,MS R-14, Cincinnati, OH 45226 USA. EM bcurwin@cdc.gov RI Barr, Dana/E-6369-2011; Barr, Dana/E-2276-2013 NR 35 TC 31 Z9 31 U1 2 U2 15 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1053-4245 J9 J EXPO ANAL ENV EPID JI J. Expo. Anal. Environ. Epidemiol. PD NOV PY 2005 VL 15 IS 6 BP 500 EP 508 DI 10.1038/sj.jea.7500428 PG 9 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 984ZB UT WOS:000233344800006 PM 15841098 ER PT J AU Swartz, KJ AF Swartz, KJ TI Structure and anticipatory movements of the S6 gate in K-v channels SO JOURNAL OF GENERAL PHYSIOLOGY LA English DT Editorial Material ID SHAKER POTASSIUM CHANNEL; GATING CHARGE MOVEMENT; ACTIVATION GATE; VOLTAGE-SENSOR; CRYSTAL-STRUCTURE; OPEN STATE; TRANSITIONS; PORE; MECHANISM; CURRENTS C1 NINDS, Mol Physiol & Biophys Sect, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA. RP Swartz, KJ (reprint author), NINDS, Mol Physiol & Biophys Sect, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA. EM swartzk@ninds.nih.gov FU Intramural NIH HHS [ZIA NS002945-13] NR 43 TC 8 Z9 8 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1295 J9 J GEN PHYSIOL JI J. Gen. Physiol. PD NOV PY 2005 VL 126 IS 5 BP 413 EP 417 DI 10.1085/jgp.200509430 PG 5 WC Physiology SC Physiology GA 986PC UT WOS:000233461200001 PM 16260835 ER PT J AU Beatty, L Jones, D Doctor, L AF Beatty, L Jones, D Doctor, L TI Reducing HIV/AIDS and criminal justice involvement in African Americans as a consequence of drug abuse SO JOURNAL OF HEALTH CARE FOR THE POOR AND UNDERSERVED LA English DT Editorial Material C1 NIDA, NIH, Special Populat Off, Bethesda, MD 20892 USA. NIDA, NIH, Serv Res Branch, Div Epidemiol Serv & Prevent Res, Bethesda, MD 20892 USA. RP Beatty, L (reprint author), NIDA, NIH, Special Populat Off, Bethesda, MD 20892 USA. EM lbeatty@nida.nih.gov NR 4 TC 6 Z9 6 U1 0 U2 0 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4363 USA SN 1049-2089 J9 J HEALTH CARE POOR U JI J. Health Care Poor Underserved PD NOV PY 2005 VL 16 IS 4 SU B BP 1 EP 5 DI 10.1353/hpu.2005.0107 PG 5 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 992IT UT WOS:000233878300001 PM 16327102 ER PT J AU Anderson, JB AF Anderson, JB TI Unraveling health disparities: Examining the dimensions of hypertension and diabetes through community engagement SO JOURNAL OF HEALTH CARE FOR THE POOR AND UNDERSERVED LA English DT Article; Proceedings Paper CT Network Research Conference on Racial Disparities in Health Outcomes CY SEP, 2004 CL Morehouse Sch Med, Natl Ctr Primary Care, Atlanta, GA SP Natl Hist Black Coll & Univ, Res Network for Hlth Serv & Hlth Disparities HO Morehouse Sch Med, Natl Ctr Primary Care DE health disparities; community-based participatory research; stages of change; health attitudes and beliefs AB The contexts of people's lives can perpetuate racial and ethnic health disparities. In this work, community members from four racial/ethnic groups (Hispanic, Native American, African American, Asian) engaged in an investigative process to analyze their own life conditions, and to explore dimensions of their health behaviors and lifestyles when managing diabetes and/or hypertension. Principal conclusions of the researchers: (1) Respondents were knowledgeable about their health conditions, but had no knowledge of health disparities. (2) Respondents felt the media portrays members of racial/ethnic minorities as hopeless and helpless; this discourages them from believing they can live healthier or better lives. (3) The over-abundance of fast food and unhealthy food eateries in minority communities contradicts the advice of the public health industry. (4) The majority of all respondents were in one of two stages relative to their willingness to change unhealthy behaviors: not interested or already doing it. C1 Univ Maryland Baltimore Cty, Baltimore, MD 21228 USA. NICHD, NIH, Bethesda, MD 20892 USA. RP Anderson, JB (reprint author), Univ Maryland Baltimore Cty, Baltimore, MD 21228 USA. EM Andersju@mail.nih.gov NR 28 TC 13 Z9 13 U1 0 U2 2 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4363 USA SN 1049-2089 J9 J HEALTH CARE POOR U JI J. Health Care Poor Underserved PD NOV PY 2005 VL 16 IS 4 SU A BP 91 EP 117 DI 10.1353/hpu.2005.0121 PG 27 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 992IR UT WOS:000233878100009 PM 16327099 ER PT J AU Ayabe, F Katoh, M Inoue, T Kouprina, N Larionov, V Oshimura, M AF Ayabe, F Katoh, M Inoue, T Kouprina, N Larionov, V Oshimura, M TI A novel expression system for genomic DNA loci using a human artificial chromosome vector with transformation-associated recombination cloning SO JOURNAL OF HUMAN GENETICS LA English DT Article DE genomic expression; human artificial chromosome (HAC) vector; transformation-associated recombination (TAR) cloning; TAR-HAC combination system; HPRT (hypoxanthine guanine phosphoribosyl transferase) ID GENE; CELLS; YEAST; DISEASE; CONSTRUCTION; INTEGRATION; SEQUENCE; MICE AB Following the recent completion of the human genome sequence, genomics research has shifted its focus to understanding gene complexity, expression, and regulation. However, in order to investigate such issues, there is a need to develop a practical system for genomic DNA expression. Transformation-associated recombination (TAR) cloning has proven to be a convenient tool for selective isolation of a genetic locus from a complex genome as a circular YAC using recombination in yeast. The human artificial chromosome (HAC) vector containing an acceptor loxP site has served as a platform for the reproducible expression of transgenes. In this study, we describe a system that efficiently expresses a genetic locus in mammalian cells by retrofitting a TAR-YAC with the donor loxP site and loading it onto the HAC vector by the Cre/loxP system. In order to demonstrate functional expression of genomic loci, the entire human hypoxanthine phosphoribosyl transferase (HPRT) locus contained in a 100 kb YAC was loaded onto the HAC vector and was shown to complement the genetic defect in Hprt-deficient CHO cells. Thus, the combination of TAR cloning and the HAC vector may serve as a powerful tool for functional genomic studies. C1 Tottori Univ, Grad Sch Med Sci, Inst Regenerat Med & Biofunct, Dept Biomed Sci, Tottori 6838503, Japan. Tottori Univ, Grad Sch Med Sci, Dept Human Genome Sci, Tottori 6838503, Japan. NCI, Lab Biosyst & Canc, NIH, Bethesda, MD 20892 USA. RP Oshimura, M (reprint author), Tottori Univ, Grad Sch Med Sci, Inst Regenerat Med & Biofunct, Dept Biomed Sci, 86 Nishi Cho, Tottori 6838503, Japan. EM oshimura@grape.med.tottori-u.ac.jp NR 25 TC 20 Z9 21 U1 0 U2 2 PU SPRINGER TOKYO PI TOKYO PA 3-3-13, HONGO, BUNKYO-KU, TOKYO, 113-0033, JAPAN SN 1435-232X J9 J HUM GENET JI J. Hum. Genet. PD NOV PY 2005 VL 50 IS 11 BP 592 EP 599 DI 10.1007/s10038-005-0300-6 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 985LG UT WOS:000233378400007 PM 16231070 ER PT J AU Zelinka, T Strauch, B Petrak, O Holaj, R Vrankova, A Weisserova, H Pacak, K Widimsky, J AF Zelinka, Tomas Strauch, Branislav Petrak, Ondrej Holaj, Robert Vrankova, Alice Weisserova, Hana Pacak, Karel Widimsky, Jiri, Jr. TI Increased blood pressure variability in pheochromocytoma compared to essential hypertension patients SO JOURNAL OF HYPERTENSION LA English DT Article ID BETA-ADRENERGIC RECEPTORS; ORTHOSTATIC HYPOTENSION; PROGNOSTIC-SIGNIFICANCE; ATHEROSCLEROSIS; MANAGEMENT; OHASAMA; DAMAGE AB Objective Catecholamines are responsible for short and long-lasting blood pressure (BP) elevations in pheochromocytoma. We investigated whether in patients with pheochromocytoma this catecholamine excess would result in higher BP variability in comparison with patients suffering from essential hypertension (EH). Design We examined retrospectively 54 (26 treated with alpha(1)-blockers) patients with pheochromocytoma (30 patients also investigated after tumour removal) and 108 (42 treated with alpha(1)-blockers) patients with EH. They all underwent 24-h ambulatory BP monitoring. To assess the BP variability, coefficient of BP variability (SD of average BP/average BP) was used. Results In subjects with pheochromocytoma, a higher coefficient of BP variability was shown compared with EH during the 24-h period (0.12 +/- 0.03 versus 0.10 +/- 0.02, P = 0.003 for systolic BP in the treated group) and mainly during the daytime (0.11/0.13 +/- 0.04/0.03 versus 0.09/0.11 +/- 0.03/0.04, P = 0.007/0.06 for systolic/diastolic BP in the untreated group and 0.12/0.13 +/- 0.04/0.04 versus 0.09/0.12 +/- 0.04/0.02, P < 0.001/0.01 in the treated group). Tumour removal resulted in a decrease of the previously increased 24-h (0.11 +/- 0.03 versus 0.10 +/- 0.03, P = 0.04) and daytime (0.11 +/- 0.03 versus 0.09 W 0.03, P U 0.03) coefficient of systolic BP variation. Twenty-seven subjects with pheochromocytoma and inverted circadian BP rhythm (night-time BP > daytime BP) had a significantly higher 24-h (0.13 +/- 0.03 versus 0.10 +/- 0.03, P < 0.001 for systolic BP) and daytime coefficient of BP variation (0.13/0.15 +/- 0.04/0.03 versus 0.09/0.12 +/- 0.02/0.02, P < 0.001/< 0.001) and also a higher occurrence of the isolated excretion of norepinephrine (14 versus seven subjects, P = 0.05) compared with the 27 subjects with pheochromocytoma without inverted circadian BP rhythm. Conclusion The excess of catecholamines in patients with pheochromocytoma is associated with higher long-term BP variability in comparison with patients suffering from EH especially in subjects with inverted circadian BP rhythm. Tumour removal resulted in the amelioration of the previously increased BP variability. C1 Gen Fac Hosp, Dept Med 3, CZ-12808 Prague 2, Czech Republic. NICHHD, Reprod Endocrinol & Med Branch, NIH, Bethesda, MD 20892 USA. RP Zelinka, T (reprint author), Gen Fac Hosp, Dept Med 3, U Nemocnice 1, CZ-12808 Prague 2, Czech Republic. EM tzeli@lf1.cuni.cz RI Petrak, Ondrej/A-5839-2017; Vrankova, Alice/C-2516-2017; Holaj, Robert/D-4241-2017; Strauch, Branislab/D-4274-2017; Zelinka, Tomas/D-4276-2017 OI Petrak, Ondrej/0000-0001-8992-3562; Vrankova, Alice/0000-0002-2327-2338; Holaj, Robert/0000-0002-9488-9706; Strauch, Branislab/0000-0001-5137-7017; Zelinka, Tomas/0000-0003-3395-8373 NR 28 TC 24 Z9 24 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0263-6352 J9 J HYPERTENS JI J. Hypertens. PD NOV PY 2005 VL 23 IS 11 BP 2033 EP 2039 DI 10.1097/01.hjh.0000185714.60788.52 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 067GT UT WOS:000239290600018 PM 16208146 ER PT J AU Saavedra, JM AF Saavedra, Juan M. TI Studies on genes and hypertension - Reply SO JOURNAL OF HYPERTENSION LA English DT Letter C1 NIMH, Div Intramural Res Programs, Pharmacol Sect, Dept Hlth & Human Serv,NIH, Bethesda, MD 20892 USA. RP Saavedra, JM (reprint author), NIMH, Div Intramural Res Programs, Pharmacol Sect, Dept Hlth & Human Serv,NIH, 10 Ctr Dr,Bldg 10 Room 2D-57, Bethesda, MD 20892 USA. EM saavedrj@mail.nih.gov NR 2 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0263-6352 J9 J HYPERTENS JI J. Hypertens. PD NOV PY 2005 VL 23 IS 11 BP 2110 EP 2111 DI 10.1097/01.hjh.0000186836.63996.0f PG 2 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 067GT UT WOS:000239290600029 ER PT J AU Park, IK Shultz, LD Letterio, JJ Gorham, JD AF Park, IK Shultz, LD Letterio, JJ Gorham, JD TI TGF-beta 1 inhibits T-bet induction by IFN-gamma in murine CD4(+) T cells through the protein tyrosine phosphatase Src homology region 2 domain-containing phosphatase-1 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID GROWTH-FACTOR-BETA; TRANSCRIPTION FACTOR IRF-1; CLASS-II TRANSACTIVATOR; TGF-BETA; GENE-EXPRESSION; IMMUNE-RESPONSES; INTERFERON-GAMMA; TRANSFORMING GROWTH-FACTOR-BETA-1; SIGNAL-TRANSDUCTION; PHOSPHORYLATION AB TGF-beta 1 prevents the development of autoimmune disease by restraining the development of autoreactive Th1 cells. TGF-beta 1 inhibits Th1 development in part by suppressing the expression of T-bet, an IFN-gamma-induced transcription factor that promotes Th1 differentiation, but how TGF-beta 1 suppresses T-bet is not known. In this study we show that TGF-beta 1 suppresses IFN-gamma-induced T-bet expression through the hemopoietic protein tyrosine phosphatase (PTP) Src homology region 2 domain-containing phosphatase-1 (Shp-1). In murine CD4(+) T cells, IFN-gamma rapidly induced the expression of T-bet as well as of IFN regulatory factor-1, another transcription factor important for Th1 development. TGF-beta 1 antagonized the effects of IFN-gamma, inhibiting IFN-gamma's induction of both Th1 transcription factors. In the presence of IFN-gamma, TGF-beta 1 rapidly induced in Th cells the synthesis of the PTP Shp-1, but did not induce Shp-2 or several members of the suppressor of cytokine signaling family of Jak-Stat inhibitors. We tested the requirement for Shp-1 by using T cells from the Shp-1-deficient me(v)/me(v) mouse strain. Shp-1 was required for TGF-beta 1's suppressive effects, because its suppression of T-bet and IFN regulatory factor-1 was completely abrogated in me(v)/me(v) CD4(+) T cells. Receptor-proximal responses to IFN-gamma, such as the induction of Jak-Stat phosphorylation, were inhibited by TGF-beta 1 in wild-type T cells, but not in me(v)/me(v) T cells. Consistent with a direct role for Shp-1, TGF-beta 1's inhibition of IFN-gamma-induced Stat1 phosphorylation was sensitive to the general PTP inhibitor pervanadate. Together, these data show that TGF-beta 1 suppresses IFN-gamma signaling and transcriptional responses in CD4(+) T cells through the PTP Shp-1. C1 Dartmouth Coll Sch Med, Dept Pathol & Microbiol, Lebanon, NH 03756 USA. Dartmouth Coll Sch Med, Dept Immunol, Lebanon, NH 03756 USA. Jackson Lab, Bar Harbor, ME 04609 USA. Natl Inst Hlth, Lab Cell Regulat & Carcinogenesis, Ctr Canc Res, Bethesda, MD 20892 USA. Natl Inst Hlth, Mol Biol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Gorham, JD (reprint author), Dartmouth Coll Sch Med, Dept Pathol & Microbiol, 1 Med Ctr Dr, Lebanon, NH 03756 USA. EM James.D.Gorham@Dartmouth.edu FU NCI NIH HHS [CA20408]; NCRR NIH HHS [P20RR16437]; NIAID NIH HHS [AI053056] NR 42 TC 55 Z9 57 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 NOV 1 PY 2005 VL 175 IS 9 BP 5666 EP 5674 PG 9 WC Immunology SC Immunology GA 977EW UT WOS:000232786300018 PM 16237056 ER PT J AU Yamada, A Sheikh, F Niimi, T DeMayo, FJ Keegan, AD Donnelly, RP Kimura, S AF Yamada, A Sheikh, F Niimi, T DeMayo, FJ Keegan, AD Donnelly, RP Kimura, S TI Induction of uteroglobin-related protein 2 (Ugrp2) gene expression by the Th2 cytokines IL-4 and IL-13 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INTERLEUKIN-4-INDUCED TRANSCRIPTION FACTOR; HUMAN-MONOCYTES; INTERFERON-GAMMA; SIGNAL-TRANSDUCTION; IFN-GAMMA; EPITHELIAL-CELLS; RECEPTOR; STAT6; LUNG; MOUSE AB Uteroglobin-related proteins 1 and 2 (UGRP1 and -2) are thought to play important roles in inflammation and immunologic responses in the lung. In this study we demonstrate that IL-4 and IL-13 enhance Ugrp2 gene expression in the mouse transformed Clara cell line, mtCC, in a time- and dose-dependent manner. Addition of actinomycin D abrogated the IL-4- and IL-13-induced increase of Ugrp2 expression, demonstrating that this increase occurs at the transcriptional level. When mtCC cells were pretreated with IFN-gamma before the addition of IL-4 or IL-13, IL-4- and 13-induced Ugrp2 mRNA increase was markedly decreased. IL-4 and IL-13 induced phosphorylation of STAT6 in mtCC cells, which binds to the proximal STAT-binding element (SBE) in the Ugrp2 gene promoter, leading to transcriptional activation of this gene. Mutations of the proximal SBE abrogated the binding of activated STAT6 to this site and the IL-4-induced increase in Ugrp2 gene promoter activity. IFN-gamma-activated STAT1 binds to the same SBE in the Ugrp2 gene promoter to which STAT6 binds and decreases the binding of STAT6 to this site. Furthermore, an IL-4-induced increase in Ugrp2 expression was not observed in primary cultures of lung cells derived from STAT6-deficient mice. These results indicate that Ugrp2 expression is enhanced by IL-4 and IL-13 through STAT6 binding to the proximal SBE located in the Ugrp2 gene promoter. C1 Natl Inst Hlth, Natl Canc Inst, Lab Metab, Bethesda, MD 20892 USA. US FDA, Ctr Drug Evaluat & Res, Div Therapeut Prot, Rockville, MD 20857 USA. Baylor Coll Med, Dept Mol & Cell Biol, Houston, TX 77030 USA. Univ Maryland, Ctr Vasc & Inflammatory Dis, Baltimore, MD 21201 USA. RP Kimura, S (reprint author), Natl Inst Hlth, Natl Canc Inst, Lab Metab, Bldg 37,Room 3112B, Bethesda, MD 20892 USA. EM shioko@helix.nih.gov FU Intramural NIH HHS [Z01 BC010449-06, Z99 CA999999] NR 56 TC 14 Z9 14 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 NOV 1 PY 2005 VL 175 IS 9 BP 5708 EP 5715 PG 8 WC Immunology SC Immunology GA 977EW UT WOS:000232786300023 PM 16237061 ER PT J AU Foley, JE Jung, U Miera, A Borenstein, T Mariotti, J Eckhaus, M Bierer, BE Fowler, DH AF Foley, JE Jung, U Miera, A Borenstein, T Mariotti, J Eckhaus, M Bierer, BE Fowler, DH TI Ex vivo rapamycin generates donor Th2 cells that potently inhibit graft-versus-host disease and graft-versus-tumor effects via an IL-4-dependent mechanism SO JOURNAL OF IMMUNOLOGY LA English DT Article ID BONE-MARROW-TRANSPLANTATION; T-CELLS; PHOSPHATIDYLINOSITOL 3-KINASE; CYCLE PROGRESSION; ADOPTIVE TRANSFER; IN-VIVO; SIROLIMUS; CD4(+); TYPE-2; DIFFERENTIATION AB Rapamycin (sirolimus) inhibits graft-vs-host disease (GVHD) and polarizes T cells toward Th2 cytokine secretion after allogeneic bone marrow transplantation (BMT). Therefore, we reasoned that ex vivo rapamycin might enhance the generation of donor Th2 cells capable of preventing GVHD after fully MHC-disparate murine BMT. Using anti-CD3 and anti-CD28 costimulation, CD4(+) Th2 cell expansion was preserved partially in high-dose rapamycin (10 mu M; Th2.rapa cells). Th2.rapa cells secreted IL-4 yet had reduced IL-5, IL-10, and IL-13 secretion relative to control Th2 cells. BMT cohorts receiving wild-type (WT) Th2.rapa cells, but not Th2.rapa cells generated from IL-4-deficient (knockout) donors, had marked Th2 skewing post-BMT and greatly reduced donor anti-host T cell alloreactivity. Histologic studies demonstrated that Th2.rapa cell recipients had near complete abrogation of skin, liver, and gut GVHD. Overall survival in recipients of WT Th2.rapa cells, but not IL-4 knockout Th2.rapa cells, was constrained due to marked attenuation of an allogeneic graft-vs-tumor (GVT) effect against host-type breast cancer cells. Delay in Th2.rapa cell administration until day 4, 7, or 14 post-BMT enhanced GVT effects, moderated GVHD, and improved overall survival. Therefore, ex vivo rapamycin generates enhanced donor Th2 cells for attempts to balance GVHD and GVT effects. C1 NCI, NIH, Expt Transplantat & Immuno Branch, Bethesda, MD 20892 USA. NIH, Div Vet Resources, Off Res Serv, Bethesda, MD 20892 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Fowler, DH (reprint author), NCI, NIH, Expt Transplantat & Immuno Branch, 9000 Rockville Pike,Bldg 10,Room 12N226, Bethesda, MD 20892 USA. EM dhfowler@helix.nih.gov FU Intramural NIH HHS NR 54 TC 45 Z9 46 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 NOV 1 PY 2005 VL 175 IS 9 BP 5732 EP 5743 PG 12 WC Immunology SC Immunology GA 977EW UT WOS:000232786300026 PM 16237064 ER PT J AU Allen, S Read, S DiPaolo, R McHugh, RS Shevach, EM Gleeson, PA van Driel, IR AF Allen, S Read, S DiPaolo, R McHugh, RS Shevach, EM Gleeson, PA van Driel, IR TI Promiscuous thymic expression of an autoantigen gene does not result in negative selection of pathogenic T cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ATPASE BETA-SUBUNIT; THYMECTOMY AUTOIMMUNE GASTRITIS; H,K-ATPASE ALPHA-SUBUNIT; TCR TRANSGENIC MICE; EPITHELIAL-CELLS; PARIETAL-CELLS; H+,K+-ADENOSINE TRIPHOSPHATASE; GASTRITOGENIC EPITOPE; TOLERANCE; IDENTIFICATION AB "Promiscuous" thymic expression of peripheral autoantigens can contribute to immunological tolerance in some cases. However, in this study we show that thymic mRNA expression alone cannot predict a contribution to thymic tolerance. Autoimmune gastritis is caused by CD4(+) T cells directed to the alpha (H/K alpha) and beta (H/K beta) subunits of the gastric membrane protein the H+/K+ ATPase. H/K alpha mRNA is expressed in the thymus, but H/K beta expression is barely detectable. In this study,me demonstrate that thymic H/K alpha in wild-type mice or mice that overexpressed H/K alpha did not result in negative selection of pathogenic anti-H/K alpha T cells. However, negative selection of anti-H/K alpha T cells did occur if H/K beta was artificially overexpressed in the thymus. Given that H/K alpha cannot be exported from the endoplasmic reticulum and is rapidly degraded in the absence of H/K beta, we conclude that H/K alpha epitopes are unable to access MHC class II loading compartments in cells of the normal thymus. This work, taken together, with our previous studies, highlights that thymic autoantigen expression does not necessarily result in the induction of tolerance. C1 Univ Melbourne, Dept Biochem, Parkville, Vic 3010, Australia. Univ Melbourne, Bio21 Mol Sci & Biotechnol Inst, Parkville, Vic 3010, Australia. NIAID, Cellular Immunol Sect, NIH, Bethesda, MD 20892 USA. Malaghan Inst Med Res, Wellington, New Zealand. RP van Driel, IR (reprint author), Univ Melbourne, Dept Biochem, Parkville, Vic 3010, Australia. EM i.vandriel@unimelb.edu.au OI van Driel, Ian/0000-0001-5371-120X NR 35 TC 22 Z9 22 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 NOV 1 PY 2005 VL 175 IS 9 BP 5759 EP 5764 PG 6 WC Immunology SC Immunology GA 977EW UT WOS:000232786300029 PM 16237067 ER PT J AU Cohen, CJ Zheng, ZL Bray, R Zhao, YB Sherman, LA Rosenberg, SA Morgan, RA AF Cohen, CJ Zheng, ZL Bray, R Zhao, YB Sherman, LA Rosenberg, SA Morgan, RA TI Recognition of fresh human tumor by human peripheral blood lymphocytes transduced with a bicistronic retroviral vector encoding a murine anti-p53 TCR SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CYTOTOXIC T-LYMPHOCYTES; WILD-TYPE P53; SEQUENCE P53(264-272) PEPTIDE; ANTITUMOR IMMUNE-RESPONSE; MEDIATED GENE-TRANSFER; CELL-TRANSFER THERAPY; LI-FRAUMENI-SYNDROME; RECEPTOR BETA-CHAIN; CANCER-PATIENTS; HIGH-AFFINITY AB The p53 protein is markedly up-regulated in a high proportion of human malignancies. Using an HLA-A2 transgenic mouse model, it was possible to isolate high-avidity murine CTLs that recognize class I-restricted human p53 epitopes. We isolated the alpha- and beta-chain of a TCR from a highly avid murine CTL clone that recognized the human p53(264-272) epitope. These genes were cloned into a retroviral vector that mediated high efficiency gene transfer into primary human lymphocytes. Efficiencies of >90% for gene transfer into lymphocytes were obtained without selection for transduced cells. The p53 TCR-transduced lymphocytes were able to specifically recognize with high-avidity, peptide-pulsed APCs as well as HLA-A2.1(+) cells transfected with either wild-type or mutant p53 protein. p53 TCR-transduced cells demonstrated recognition and killing of a broad spectrum of human tumor cell lines as well as recognition of fresh human tumor cells. Interestingly, both CD8(+) and CD4(+) subsets were capable of recognizing and Ming target cells, stressing the potential application of such a CD8-independent TCR molecule that can mediate both helper and cytotoxic responses. These results suggest that lymphocytes genetically engineered to express anti-p53 TCR may be of value for the adoptive immunotherapy of patients with a variety of common malignancies. C1 NCI, Surg Branch, NIH, Canc Res Ctr, Bethesda, MD 20892 USA. Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA. RP Morgan, RA (reprint author), NCI, Surg Branch, NIH, Canc Res Ctr, Bldg 10,Room 3W5940,10 Ctr Dr,MSC 1201, Bethesda, MD 20892 USA. EM rmorgan@mail.nih.gov FU NCI NIH HHS [Z01 SC003811-31] NR 73 TC 83 Z9 86 U1 1 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 2005 VL 175 IS 9 BP 5799 EP 5808 PG 10 WC Immunology SC Immunology GA 977EW UT WOS:000232786300034 PM 16237072 ER PT J AU Finkelstein, LD Shimizu, Y Schwartzberg, PL AF Finkelstein, LD Shimizu, Y Schwartzberg, PL TI Tec kinases regulate TCR-mediated recruitment of signaling molecules and integrin-dependent cell adhesion SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-CELLS; IMMUNOLOGICAL SYNAPSE; PKC-THETA; RAP1-INDUCED ADHESION; ANTIGEN RECEPTOR; FAMILY KINASES; ACTIVATION; ITK; LFA-1; VAV AB T cells deficient in the Tee kinases Itk or Itk and Rlk exhibit defective TCR-stimulated proliferation, IL-2 production, and activation of phospholipase C-gamma. Evidence also implicates Tee kinases in actin cytoskeleton regulation, which is necessary for cell adhesion and formation of the immune synapse in T lymphocytes. In this study we show that Tee kinases are required for TCR-mediated up-regulation of adhesion via the LFA-1 integrin. We also demonstrate that the defect in adhesion is associated with defective clustering of LFA-1 and talin at the site of interaction of Rlk(-/-)Itk(-/-) and Itk(-/-) T cells with anti-TCR-coated beads. Defective recruitment of Vav1, protein kinase C theta, and Pyk2 was also observed in Rlk(-/-)Itk(-/-) and Itk(-/-) T cells. Stimulation with ICAM-2 in conjunction with anti-TCR-coated beads enhanced polarization of Vav1, protein kinase C theta, and Pyk2 in wild-type cells, demonstrating a role for integrins in potentiating the recruitment of signaling molecules in T cells. Increased recruitment of signaling molecules was most pronounced under conditions of low TCR stimulation. Under these suboptimal TCR stimulation conditions, ICAM-2 could also enhance the recruitment of signaling molecules in Itk(-/-), but not Rlk(-/-)Itk(-/-) T cells. Thus, Tee kinases play key roles in regulating TCR-mediated polarization of integrins and signaling molecules to the site of TCR stimulation as well as the up-regulation of integrin adhesion. C1 NHGRI, NIH, Bethesda, MD 20892 USA. Univ Minnesota, Dept Lab Med & Pathol, Ctr Immunol, Minneapolis, MN 55455 USA. Univ Minnesota, Ctr Canc, Minneapolis, MN 55455 USA. RP Schwartzberg, PL (reprint author), NHGRI, NIH, 49-4A35, Bethesda, MD 20892 USA. EM pains@mail.nih.gov OI Shimizu, Yoji/0000-0001-9760-0288 FU Intramural NIH HHS NR 44 TC 35 Z9 35 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 NOV 1 PY 2005 VL 175 IS 9 BP 5923 EP 5930 PG 8 WC Immunology SC Immunology GA 977EW UT WOS:000232786300047 PM 16237085 ER PT J AU Iribarren, P Chen, KQ Hu, JY Zhang, X Gong, WH Wang, JM AF Iribarren, P Chen, KQ Hu, JY Zhang, X Gong, WH Wang, JM TI IL-4 inhibits the expression of mouse formyl peptide receptor 2, a receptor for amyloid beta(1-42), in a TNF-alpha-Activated microglia SO JOURNAL OF IMMUNOLOGY LA English DT Article ID FORMYL PEPTIDE RECEPTOR-2; ALZHEIMERS-DISEASE; PROTEIN-KINASE; SIGNALING PATHWAYS; UP-REGULATION; MAP KINASE; CELL-LINE; INFLAMMATION; MACROPHAGES; MECHANISMS AB Microglia are phagocytic cells in the CNS and actively participate in proinflammatory responses in neurodegenerative diseases. We have previously shown that TNF-alpha up-regulated the expression of formyl peptide receptor 2 (mFPR2) in mouse microglial cells, resulting in increased chemotactic responses of such cells to mFPR2 agonists, including amyloid beta(1-42) (A beta(42)), a critical pathogenic agent in Alzheimer's disease. In the present study, we found that IL-4, a Th2-type cytokine, markedly inhibited TNF-alpha-induced expression of mFPR2 in microglial cells by attenuating activation of ERK and p38 MAPK as well as NF-kappa B. The effect of IL-4 was not dependent on Stat6 but rather required the protein phosphatase 2A (PP2A) as demonstrated by the capacity of PP2A small interfering RNA to reverse the effect of IL-4 in TNF-alpha-activated microglia. Since both IL-4 and TNF-alpha are produced in the CNS under pathophysiological conditions, our results suggest that IL-4 may play an important role in the maintenance of CNS homeostasis by limiting microglial activation by proinflammatory stimulants. C1 NCI, Mol Immunoregulat Lab, Ctr Canc Res, Frederick, MD 21702 USA. NCI, Expt Immunol Lab, Ctr Canc Res, Frederick, MD 21702 USA. SAIC Frederick, Basic Res Program, Ft Detrick, MD 21702 USA. RP Wang, JM (reprint author), NCI, Mol Immunoregulat Lab, Ctr Canc Res, Bldg 560,Room 31-40, Frederick, MD 21702 USA. EM wangji@mail.ncifcrf.gov RI Zhang, Xia/B-8152-2008 OI Zhang, Xia/0000-0002-9040-1486 NR 42 TC 22 Z9 22 U1 1 U2 6 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 2005 VL 175 IS 9 BP 6100 EP 6106 PG 7 WC Immunology SC Immunology GA 977EW UT WOS:000232786300068 PM 16237106 ER PT J AU Skapenko, A Kalden, JR Lipsky, PE Schulze-Koops, H AF Skapenko, A Kalden, JR Lipsky, PE Schulze-Koops, H TI The IL-4 receptor alpha-chain-binding cytokines, IL-4 and IL-13, induce forkhead box P3-expressing CD25(+)CD4(+) regulatory T cells from CD25(-)CD4(+) precursors SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IMMUNOLOGICAL SELF-TOLERANCE; TRANSCRIPTION FACTOR FOXP3; HUMAN PERIPHERAL-BLOOD; GROWTH-FACTOR-BETA; DENDRITIC CELLS; IN-VIVO; CD4(+) CD25(+); TGF-BETA; RHEUMATOID-ARTHRITIS; AUTOIMMUNE-DISEASE AB The mechanisms underlying the extrathymic generation of CD25(+)CD4 regulatory T cells (Tregs) are largely unknown. In this study the IL-4R alpha-chain-binding cytokines, IL-4 and IL-13, were identified as inducers of CD25(+) Tregs from peripheral CD25(-)CD4 naive T cells. IL-4-induced CD25(+) Tregs phenotypically and functionally resemble naturally occurring Tregs in that they are anergic to mitogenic stimulation, inhibit the proliferation of autologous responder T cells, express high levels of the Forkhead box P3 and the surface receptors glucocorticoid-induced TNFR family-related protein and CTLA-4, and inhibit effector T cells in a contact-dependent, but cytokine-independent, manner. The IL-4-induced generation of peripheral Tregs was independent of the presence of TGF-beta or IL-10, but was dependent on Ag-specific stimulation and B7 costimulation. The significance of the IL-4R alpha-binding cytokines in the generation of Ag-specific Tregs was emphasized in a mouse model of oral tolerance, in which neutralization of IL-4 and IL-13 in mice transgenic for the TCR specific for OVA completely inhibited the expansion of OVA-specific Tregs that can be induced in untreated mice by feeding the nominal Ag. Together, (our results demonstrate that IL-4 and IL-13 play an important role in generating Forkhead box P3-expressing CD25(+) Tregs extrathymically in an Ag-dependent manner and,therefore provide an intriguing link between the well-established immunoregulatory capacity of Th2 cells and the powerful CD25(+) Treg population. Moreover, our findings might provide the basis for the design of novel therapeutic approaches for targeted immunotherapy with Tregs to known Ags in autoimmune diseases or graft-vs-host reactions. C1 Univ Erlangen Nurnberg, Nikolaus Fiebiger Ctr Mol Med, Clin Res Grp 3, D-91054 Erlangen, Germany. Univ Erlangen Nurnberg, Dept Internal Med 3, D-91054 Erlangen, Germany. Univ Erlangen Nurnberg, Inst Clin Immunol, D-91054 Erlangen, Germany. NIH, Natl Inst Arthritis & Musculoskeletal & Skin Dis, Bethesda, MD 20892 USA. RP Schulze-Koops, H (reprint author), Univ Erlangen Nurnberg, Nikolaus Fiebiger Ctr Mol Med, Clin Res Grp 3, Glueckstr 6, D-91054 Erlangen, Germany. EM schulze-koops@med3.imed.uni-erlangen.de NR 55 TC 109 Z9 114 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 NOV 1 PY 2005 VL 175 IS 9 BP 6107 EP 6116 PG 10 WC Immunology SC Immunology GA 977EW UT WOS:000232786300069 PM 16237107 ER PT J AU Mongini, PKA Inman, JK Han, H Kalled, SL Fattah, RJ McCormick, S AF Mongini, PKA Inman, JK Han, H Kalled, SL Fattah, RJ McCormick, S TI Innate immunity and human B cell clonal expansion: Effects on the recirculating B2 subpopulation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; AUTOIMMUNE-DISEASE; CUTTING EDGE; MAST-CELLS; T-CELLS; IN-VIVO; SIGNALING PATHWAY; CYCLE PROGRESSION; SJOGRENS-SYNDROME; ANTIGEN RECEPTOR AB Foci of autoantigen-specific B lymphocytes in nonlymphoid tissues have been associated with development of amoimmune disease. To better understand the genesis of such ectopic lymphoid tissue, this study investigated whether several B cell-tropic innate immune system molecules, known to be elevated in response to inflammatory stimuli, can cooperate in fostering the T cell-independent clonal expansion of mature human B2 cells under conditions of limiting BCR engagement. Notable synergy was observed between BCR coligation with the C3dg-binding CD21/CD19 costimulatory complex, B cell-activating factor belonging to the TNF family (BAFF), and IL-4 in generating B cell progeny with sustained CD86 and DR expression. The synergy was observed over a wide range of BCR:ligand affinities and involved: 1) cooperative effects at promoting early cell cycle progression and viability; 2) BCR:CD21 coligation-promoted increases in BAFF receptors that were highly regulated by IL-4; 3) reciprocal effects of IL-4 and BAFF at dampening daughter cell apoptosis typical of stimulation by BCR:CD21 and either cytokine alone; and 4) BAFF-sustained expression of antiapoptotic Mcl-1 within replicating lymphoblasts. The results suggest that significant clonal proliferation of recirculating B2 cells occurs upon limited binding to C3dg-coated kg in an inflammatory in vivo milieu containing both BAFF and IL-4. When rare autoantigen-presenting B cells undergo such expansions, both B cell and T cell autoimmunity may be promoted. C1 NYU, Med Ctr, Dept Rheumatol, Hosp Joint Dis, New York, NY 10003 USA. NYU, Med Ctr, Dept Pathol, New York, NY 10003 USA. NIH, Immunol Lab, Bethesda, MD 20892 USA. Biogen Idec, Cambridge, MA 02142 USA. New York Eye & Ear Infirm, Dept Pathol, New York, NY 10003 USA. RP Mongini, PKA (reprint author), NYU, Med Ctr, Dept Rheumatol, Hosp Joint Dis, 301 E 17th St, New York, NY 10003 USA. EM patricia.mongini@med.nyu.edu FU NIAID NIH HHS [R01 AI052189] NR 74 TC 15 Z9 15 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 NOV 1 PY 2005 VL 175 IS 9 BP 6143 EP 6154 PG 12 WC Immunology SC Immunology GA 977EW UT WOS:000232786300073 PM 16237111 ER PT J AU Rosenberg, SA Sherry, RM Morton, KE Scharfman, WJ Yang, JC Topalian, SL Royal, RE Kammula, U Restifo, NP Hughes, MS Schwartzentruber, D Berman, DM Schwarz, SL Ngo, LT Mavroukakis, SA White, DE Steinberg, SM AF Rosenberg, SA Sherry, RM Morton, KE Scharfman, WJ Yang, JC Topalian, SL Royal, RE Kammula, U Restifo, NP Hughes, MS Schwartzentruber, D Berman, DM Schwarz, SL Ngo, LT Mavroukakis, SA White, DE Steinberg, SM TI Tumor progression can occur despite the induction of very high levels of self/tumor antigen-specific CD8(+) T cells in patients with melanoma SO JOURNAL OF IMMUNOLOGY LA English DT Article ID RECOMBINANT VACCINIA VIRUS; PHASE-I TRIAL; INCOMPLETE FREUNDS-ADJUVANT; CELLULAR IMMUNE-RESPONSES; COLONY-STIMULATING FACTOR; METASTATIC MELANOMA; PEPTIDE VACCINE; CANCER-PATIENTS; PROSTATE-CANCER; IMMUNOTHERAPY AB The identification of many tumor-associated epitopes as nonmutated "self" Ags led to the hypothesis that the induction of large numbers of self/tumor Ag-specific T cells would be prevented because of central and peripheral tolerance. We report in this study on vaccination efforts in 95 HLA-A*0201 patients at high risk for recurrence of malignant melanoma who received prolonged immunization with the "anchor-modified" synthetic peptide, gp100(209-217(210M)). Vaccination using, this altered peptide immunogen was highly effective at inducing large numbers of self/tumor-Ag reactive T cells in virtually every patient tested, with levels as high as 42% of all CD8(+) T cells assessed by tetramer analysis. From 1 to 10% of all CD8+ cells were tumor-Ag reactive in 44% of patients and levels >10% were generated in 17% of patients. These studies were substantiated using the ELISPOT assay and a bulk cytokine release assay. Although our data regarding "tumor escape" were inconclusive, some patients had growing tumors that expressed Ag and HLA-A*0201 in the presence of high levels of antitumor T cells. There was no difference in the levels of antitumor Ag-specific T cells in patients who recurred compared with those that remained disease-free. Thus, the mere presence of profoundly expanded numbers of vaccine-induced, self/tumor Ag-specific T cells cannot by themselves be used as a "surrogate marker" for vaccine efficacy. Further, the induction of even high levels of antitumor T cells may be insufficient to alter tumor progression. C1 NCI, Surg Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Rosenberg, SA (reprint author), NCI, NIH, Clin Res Ctr, Room 3W-3-3940,10 Ctr Dr, Bethesda, MD 20892 USA. EM sar@nih.gov RI Restifo, Nicholas/A-5713-2008; OI Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [Z01 BC010763-01, Z99 CA999999] NR 36 TC 276 Z9 290 U1 0 U2 7 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 2005 VL 175 IS 9 BP 6169 EP 6176 PG 8 WC Immunology SC Immunology GA 977EW UT WOS:000232786300076 PM 16237114 ER PT J AU Hinrichs, CS Palmer, DC Rosenberg, SA Restifio, NP AF Hinrichs, CS Palmer, DC Rosenberg, SA Restifio, NP TI Glucocorticoids do not inhibit antitumor activity of activated CD8(+) T cells SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE immunotherapy; glucocorticoid; T cell ID VERSUS-HOST-DISEASE; STEROID-RESISTANT ASTHMA; FAS-LIGAND EXPRESSION; FACTOR-KAPPA-B; INDUCED APOPTOSIS; METASTATIC MELANOMA; CANCER REGRESSION; ALLOGENEIC HEPATOCYTES; ALLOGRAFT-REJECTION; TRANSFER THERAPY AB Glucocorticoids are potent immunosuppressive drugs that are generally withheld from cancer patients receiving immunotherapy. We Sought to test the hypothesis that glucocorticoids might interfere with the function of cells after adoptive transfer. We gave dexamethasone, a potent synthetic glucocorticoid, to B16 melanoma-bearing truce receiving the adoptive cell transfer (ACT) of pmel-1 T-cell receptor transgenic CD8(+) cells. Dexamethasone caused a profound lymphodepletion but, surprisingly, did not alter the anti-tumor efficacy of ACT-based regimens whether given before, during, or after ACT. Although dexamethasone radically decreased the number of native CD8(+) splenocytes in recipient mice, it did not affect the numbers of CD8(+) pmel-1 cells derived from ACT in these mice. In vitro proliferation assays revealed acute inhibition of naive pinel-1 CD8(+) cells by dexamethasone without significant effect on activated cells. In vitro interferon (IFN)-gamma release from activated pmel-1 CD8(+) cells showed partial inhibition by dexamethasone, but this effect was relatively minor when compared with the near-complete inhibition of naive cells. Thus, gucocorticoids had a profound inhibitory effect oil naive CD8(+) T cells but had little impact on the proliferation and function of activated CD8(+) pmel-1 T cells. Finally, because glucocorticoids had no effect on tumor regression in this model, it may be possible to use glucocorticoids in some patients receiving ACT-based immunotherapy regimens. C1 NCI, Clin Res Ctr, NIH, Bethesda, MD 20892 USA. RP Restifio, NP (reprint author), NCI, Clin Res Ctr, NIH, Room 3-5816, Bethesda, MD 20892 USA. EM restifon@mail.nih.gov RI Palmer, Douglas/B-9454-2008; OI Palmer, Douglas/0000-0001-5018-5734; Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [Z99 CA999999, Z01 BC010763-01] NR 51 TC 26 Z9 26 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2005 VL 28 IS 6 BP 517 EP 524 DI 10.1097/01.cji.0000177999.95831.7b PG 8 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 978WN UT WOS:000232903800001 PM 16224268 ER PT J AU Wang, QJ Hanada, K Perry-Lalley, D Bettinotti, MP Karpova, T Khong, HT Yang, JC AF Wang, QJ Hanada, K Perry-Lalley, D Bettinotti, MP Karpova, T Khong, HT Yang, JC TI Generating renal cancer-reactive T cells using dendritic cells (DCs) to present autologous tumor SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE dendritic cells; renal cell carcinoma; T cells; apoptosis; necrosis ID APOPTOTIC CELLS; METASTATIC MELANOMA; ANTITUMOR LYMPHOCYTES; CROSS-PRESENTATION; PHASE-II; CARCINOMA; ANTIGEN; VACCINATION; IDENTIFICATION; INTERLEUKIN-2 AB Dendritic cells (DCs) have been used as professional antigen-presenting cells in vitro to prime T-cell responses. In this study, we generated both CD8(+) and CD4(+) renal cell carcinoma (RCC)-reactive T cells using a completely autologous system of DCs presenting engulfed whole-tumor cells. We compared DCs presenting RCC tumor cells in different preparations and found ultraviolet-irradiated apoptotic turner cells to be more immunogenic than necrotic tumor cells or live untreated tumor cells in generating tumor-reactive T cells. In analyzing the T cells generated in this fashion, a CD8(+) RCC-reactive T-cell clone generated from a patient recognized an epitope derived from fibroblast growth factor 5 in the context of human leukocyte antigen (HLA) B44*02. CD4(+) T cells generated from another patient recognized multiple allogeneic RCC lines expressing HLA-DR beta 1*04, indicating a common shared turner antigen presented by HLA-DR beta 1*04. The technique of using DCs to present whole-tumor cells can consistently generate both CD4(+) and CD8(+) RCC-reactive T cells for use in both antigen identification and therapeutic protocols. C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. NIH, Dept Transfus Med, Mol Immunol Lab, Bethesda, MD 20892 USA. NIH, Core Fluorescence Imaging Facil, Bethesda, MD 20892 USA. Univ S Alabama, Canc Res Inst, Mobile, AL 36688 USA. RP Yang, JC (reprint author), NCI, Surg Branch, NIH, 9000 Rockville Pike,Bldg 10-CRC,Rm 3W-3840, Bethesda, MD 20892 USA. EM James_Yang@nih.gov RI Hanada, Ken-ichi/A-4642-2008; Hanada, Ken-ichi/L-2481-2013 OI Hanada, Ken-ichi/0000-0003-2959-1257 FU Intramural NIH HHS NR 33 TC 12 Z9 15 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2005 VL 28 IS 6 BP 551 EP 559 DI 10.1097/01.cji.0000175495.13476.1f PG 9 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 978WN UT WOS:000232903800005 PM 16224272 ER PT J AU Attia, P Maker, AV Haworth, LR Rogers-Freezer, L Rosenberg, SA AF Attia, P Maker, AV Haworth, LR Rogers-Freezer, L Rosenberg, SA TI Inability of a fusion protein of IL-2 and diphtheria toxin (Denileukin Diftitox, DAB(389)IL-2, ONTAK) to eliminate regulatory T lymphocytes in patients with melanoma SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE oncology; regulatory T cells; melanoma ID HIGH-DOSE INTERLEUKIN-2; GENERATED EX-VIVO; IMMUNOLOGICAL SELF-TOLERANCE; NON-HODGKINS-LYMPHOMA; VERSUS-HOST-DISEASE; TGF-BETA; AUTOIMMUNE-DISEASE; METASTATIC MELANOMA; CANCER REGRESSION; IMMUNE-RESPONSES AB Elimination of regulatory T lymphocytes may provide a way to break self-tolerance and unleash the anti-tumor properties of circulating lymphocytes. The use of fusion proteins, which link cytotoxic molecules to receptor targets, provides one approach to this problem. This study examined the ability of a fusion protein of interleukin-2 (IL-2) and diphtheria toxin (Denileukin Diffitox, DAB(389)IL-2, ONTAK) to eliminate regulatory T lymphocytes based on their expression of high-affinity IL-2 receptors. Thirteen patients (12 with metastatic melanoma, 1 with metastatic renal cell carcinoma) were treated at one of the two Food and Drug Administration-approved doses of Denileukin Diffitox (seven patients at 9 mu g/kg, six patients at 18 mu g/kg). None of the patients experienced an objective clinical response. Foxp3 expression did not decrease significantly overall, although it did decrease minimally among patients receiving 18 mu g/kg (-2.01 +/- 0.618 copies of Foxp3/10(3) copies of beta-actin; P = 0.031). Denileukin Diffitox did not decrease the suppressive ability of CD4(+)CD25(+) cells as quantified by an in vitro co-culture suppression assay. Furthermore, the increased numbers of lymphocytes in patients resulting from treatment with IL-2 were not susceptible to Denileukin Diffitox. Administration of Denileukin Diffitox does not appear to eliminate regulatory T lymphocytes or cause regression of metastatic melanoma. C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Rosenberg, SA (reprint author), NCI, Surg Branch, NIH, 10 Ctr Dr,CRC,Rm 3W-3940, Bethesda, MD 20892 USA. EM sar@nih.gov FU NCI NIH HHS [Z01 SC003811-31] NR 61 TC 189 Z9 199 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2005 VL 28 IS 6 BP 582 EP 592 DI 10.1097/01.cji.0000175468.19742.10 PG 11 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 978WN UT WOS:000232903800009 PM 16224276 ER PT J AU Blansfield, JA Beck, KE Tran, K Yang, DC Hughes, MS Kammula, US Royal, RE Topalian, SL Haworth, LR Levy, C Rosenberg, SA Sherry, RM AF Blansfield, JA Beck, KE Tran, K Yang, DC Hughes, MS Kammula, US Royal, RE Topalian, SL Haworth, LR Levy, C Rosenberg, SA Sherry, RM TI Cytotoxic T-Lymphocyte-associated antigen-4 blockage can induce autoimmune hypophysitis in patients with metastatic melanoma and renal cancer SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE anti-CTLA-4 antibody; autoimmunity; autoimmune hypophysitis; melanoma; renal cell cancer; immunotherapy ID THERAPY; LYMPHOPROLIFERATION; ANTIBODY; DISEASE; CTLA-4; MICE AB Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) is an immunoregulatory molecule expressed by activated T cells and resting CD4(+)CD25(+) T cells. In patients with advanced melanoma, Our Group reported that administration of anti-CTLA-4 antibody mediated objective cancer regression in 13% of patients. This study also established that the blockade of CTLA-4 was associated with grade III/IV autoimmune manifestations that included dermatitis, enterocolitis, hepatitis, uveitis, and a single case of hypophysitis. Since this initial report, 7 additional patients with anti-CTLA-4 antibody-induced autoimmune hypophysitis have been accumulated. The characteristics, clinical course, laboratory values, radiographic findings, and treatment of these 8 patients are the focus of this report. C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Sherry, RM (reprint author), NCI, Surg Branch, NIH, CRC,Room 3W-5942,10 Ctr Dr, Bethesda, MD 20892 USA. EM Richard-Sherry@nih.gov FU Intramural NIH HHS [Z01 SC003811-32] NR 16 TC 193 Z9 202 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2005 VL 28 IS 6 BP 593 EP 598 DI 10.1097/01.cji.0000178913.41256.06 PG 6 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 978WN UT WOS:000232903800010 PM 16224277 ER PT J AU Perez-Diez, A Joncker, N Choi, K Chan, W Anderson, C Lantz, O Matzinger, P AF Perez-Diez, A Joncker, N Choi, K Chan, W Anderson, C Lantz, O Matzinger, P TI CD4 cells can be more efficient at tumor rejection than CD8 cells SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 20th Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY NOV 10-13, 2005 CL Alexandria, VA SP Int Soc Biol Therapy Canc C1 NIAID, Ghost Lab, Cellular & Mol Immunol Lab, NIH, Bethesda, MD 20892 USA. Inst Curie, INSERM, U520, Paris, France. Inst Curie, INSERM, Immunol Lab, Paris, France. Univ Alberta, Edmonton, AB, Canada. RI Lantz, Olivier/J-4960-2012 OI Lantz, Olivier/0000-0003-3161-7719 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2005 VL 28 IS 6 BP 617 EP 617 DI 10.1097/01.cji.0000190961.34913.e5 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 978WN UT WOS:000232903800037 ER PT J AU Provenzano, A Selleri, S Ping, J Wang, E Adams, S Panelli, M Leitman, SF Stroncek, DF Marincola, F AF Provenzano, A Selleri, S Ping, J Wang, E Adams, S Panelli, M Leitman, SF Stroncek, DF Marincola, F TI Comprehensive epitope mapping of the Epstein-Barr virus Latent Membrane Protein-2 in ethnically diverse populations SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 20th Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY NOV 10-13, 2005 CL Alexandria, VA SP Int Soc Biol Therapy Canc C1 Univ Hosp ZLF, Dept Surg, Immune Oncol Sect, Basel, Switzerland. NIH, Bethesda, MD 20892 USA. Univ Milan, Dept Human Morphol, Milan, Italy. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2005 VL 28 IS 6 BP 617 EP 617 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 978WN UT WOS:000232903800038 ER PT J AU Robbins, P AF Robbins, P TI Factors that influence responses to adoptive cancer immunotherapy SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 20th Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY NOV 10-13, 2005 CL Alexandria, VA SP Int Soc Biol Therapy Canc C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2005 VL 28 IS 6 BP 617 EP 618 DI 10.1097/01.cji.0000190963.42536.82 PG 2 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 978WN UT WOS:000232903800039 ER PT J AU Arico, E Parlato, S Capone, H Gabriele, L Rivoltini, L Wang, E Panelli, MC Lee, B Marincola, F Belardelli, F AF Arico, E Parlato, S Capone, H Gabriele, L Rivoltini, L Wang, E Panelli, MC Lee, B Marincola, F Belardelli, F TI Microarray analysis for monitoring the response to interferon SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 20th Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY NOV 10-13, 2005 CL Alexandria, VA SP Int Soc Biol Therapy Canc C1 Ist Super Sanita, I-00161 Rome, Italy. Ist Nazl Studio & Cura Tumori, I-20133 Milan, Italy. NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2005 VL 28 IS 6 BP 619 EP 620 DI 10.1097/01.cji.0000190970.95901.21 PG 2 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 978WN UT WOS:000232903800046 ER PT J AU Wrzesinski, C Gattinoni, L Palmer, DC Paulos, CM Yu, ZY Rosenberg, SA Restifo, NP AF Wrzesinski, C Gattinoni, L Palmer, DC Paulos, CM Yu, ZY Rosenberg, SA Restifo, NP TI Hematopoietic stem cell transplant with lymphodepletion augments T cell-based adoptive immunotherapy SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 20th Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY NOV 10-13, 2005 CL Alexandria, VA SP Int Soc Biol Therapy Canc C1 NCI, NIH, Bethesda, MD 20892 USA. RI Restifo, Nicholas/A-5713-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2005 VL 28 IS 6 BP 619 EP 619 DI 10.1097/01.cji.0000190968.11149.79 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 978WN UT WOS:000232903800044 ER PT J AU Jin, P Provenzano, M Panelli, MC Voiculescu, S Zavaglia, K Stroncek, D Marincola, FM Wang, E AF Jin, P Provenzano, M Panelli, MC Voiculescu, S Zavaglia, K Stroncek, D Marincola, FM Wang, E TI Molecular pathways of interleukin-2 SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 20th Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY NOV 10-13, 2005 CL Alexandria, VA SP Int Soc Biol Therapy Canc C1 NIH, Bethesda, MD 20892 USA. Univ Hosp ZLF, Dept Surg, Immune Oncol Sect, Basel, Switzerland. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2005 VL 28 IS 6 BP 621 EP 622 DI 10.1097/01.cji.0000190977.16094.95 PG 2 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 978WN UT WOS:000232903800053 ER PT J AU Lee, BM Smith, K Panelli, MC Wang, E Marincola, F Arico, E AF Lee, BM Smith, K Panelli, MC Wang, E Marincola, F Arico, E TI The alternative nature of type one interferons SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 20th Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY NOV 10-13, 2005 CL Alexandria, VA SP Int Soc Biol Therapy Canc C1 NIH, Bethesda, MD 20892 USA. Ist Super Sanita, I-00161 Rome, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2005 VL 28 IS 6 BP 622 EP 622 DI 10.1097/01.cji.0000190979.23718.79 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 978WN UT WOS:000232903800055 ER PT J AU Salcedo, R Hixon, J Stauffer, J Kha, T Lincoln, E Back, T Kastelein, R Wigginton, J AF Salcedo, R Hixon, J Stauffer, J Kha, T Lincoln, E Back, T Kastelein, R Wigginton, J TI Immunologic and therapeutic synergy of IL-27 and IL-2: Complete regression of neuroblastoma metastases in the liver and bone marrow SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 20th Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY NOV 10-13, 2005 CL Alexandria, VA SP Int Soc Biol Therapy Canc C1 SAIC, POB, Frederick, MD USA. NCI, OPOB, Frederick, MD 21701 USA. DNAX Res Inst Molec & Cellular Biol Inc, Palo Alto, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2005 VL 28 IS 6 BP 625 EP 625 DI 10.1097/01.cji.0000190987.77083.68 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 978WN UT WOS:000232903800063 ER PT J AU Subleski, A Back, TC Ortaldo, JR Wiltrout, RH AF Subleski, A Back, TC Ortaldo, JR Wiltrout, RH TI IL-18 plus IL-12 decreases liver metastases through An NK cell, IFN-gamma dependent mechanism and overcomes NK/T cell mediated suppression SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 20th Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY NOV 10-13, 2005 CL Alexandria, VA SP Int Soc Biol Therapy Canc C1 NCI, Expt Immunol Lab, CCR, Frederick, MD 21701 USA. SAIC Frederick, Intramural Res Support Program, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2005 VL 28 IS 6 BP 626 EP 626 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 978WN UT WOS:000232903800065 ER PT J AU Hixon, J Stauffer, JK Khan, T Salcedo, R Lincoln, E Back, TC Jonak, Z Dar, M Wigginton, JM AF Hixon, J Stauffer, JK Khan, T Salcedo, R Lincoln, E Back, TC Jonak, Z Dar, M Wigginton, JM TI Tumor cell IFN-gamma responsiveness mediates the generation of tumor-specific immunologic reactivity and overall antitumor activity of IL-18 in mice bearing neuroblastoma tumors SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 20th Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY NOV 10-13, 2005 CL Alexandria, VA SP Int Soc Biol Therapy Canc C1 NCI, Pediat Oncol Branch, CCR, Frederick, MD 21701 USA. SAIC Frederick, Intramural Res Support Program, Frederick, MD USA. GlaxoSmithKline Pharmaceut, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2005 VL 28 IS 6 BP 627 EP 627 DI 10.1097/01.cji.0000190994.48374.19 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 978WN UT WOS:000232903800070 ER PT J AU Yazawa, H Ortaldo, JR Back, TC Subleski, JJ Seki, N Reynolds, DM Winkler-Pickett, RT Wiltrout, RH Watanabe, M AF Yazawa, H Ortaldo, JR Back, TC Subleski, JJ Seki, N Reynolds, DM Winkler-Pickett, RT Wiltrout, RH Watanabe, M TI Hydrodynamics-based gene delivery of a novel interleukin-15 plasmid augments natural killer cell activities and suppresses lung metastasis SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 20th Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY NOV 10-13, 2005 CL Alexandria, VA SP Int Soc Biol Therapy Canc C1 NCI, LEI, CCR, Frederick, MD 21701 USA. SAIC Frederick Inc, Intramural Res Support Program, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2005 VL 28 IS 6 BP 627 EP 627 DI 10.1097/01.cji.0000190993.71245.66 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 978WN UT WOS:000232903800069 ER PT J AU Rossi, L Martin, BM Hortin, GL White, RL Foster, M Moharram, R Stroncek, D Wang, E Marincola, FM Panelli, MC AF Rossi, L Martin, BM Hortin, GL White, RL Foster, M Moharram, R Stroncek, D Wang, E Marincola, FM Panelli, MC TI Inflammatory protein profile during systemic high dose interleukin-2 administration SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 20th Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY NOV 10-13, 2005 CL Alexandria, VA SP Int Soc Biol Therapy Canc C1 NIH, DTM, Bethesda, MD 20892 USA. NIMH, NIH, Bethesda, MD 20892 USA. NIH, Dept Clin Chem, Bethesda, MD 20892 USA. Carolinas Hlth Care Org, Med Ctr, Charlotte, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2005 VL 28 IS 6 BP 628 EP 628 DI 10.1097/01.cji.0000190998.01740.e1 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 978WN UT WOS:000232903800074 ER PT J AU Shafer-Weaver, KA Zartiskaya, L Strobl, S Luck, T Baseler, M Malyguine, A AF Shafer-Weaver, KA Zartiskaya, L Strobl, S Luck, T Baseler, M Malyguine, A TI Dueling ELISPOTS: Use of the IFN-gamma, GrB, or dual color IFN-gamma/GrB ELISPOT assay for immunological monitoring SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 20th Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY NOV 10-13, 2005 CL Alexandria, VA SP Int Soc Biol Therapy Canc C1 SAIC Frederick Inc, Clin Serv Program, NCI, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2005 VL 28 IS 6 BP 634 EP 634 DI 10.1097/01.cji.0000191017.67673.f1 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 978WN UT WOS:000232903800093 ER PT J AU Stauffer, JK Greer, B Lincoln, E Back, TC Hixon, JA Whiteford, C Eisenhofer, G Tsokos, M Weiss, W Khan, J Wigginton, JM AF Stauffer, JK Greer, B Lincoln, E Back, TC Hixon, JA Whiteford, C Eisenhofer, G Tsokos, M Weiss, W Khan, J Wigginton, JM TI High-throughput molecular and histopathologic profiling of the tumor microenvironment in a novel transplantable model of murine neuroblastoma: New tools for pediatric drug discovery SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 20th Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY NOV 10-13, 2005 CL Alexandria, VA SP Int Soc Biol Therapy Canc C1 NCI, Pediat Oncol Branch, CCR, Frederick, MD 21701 USA. SAIC Frederick, IRSP, Frederick, MD USA. NINDS, Bethesda, MD 20892 USA. NCI, Pathol Lab, CCR, Bethesda, MD 20892 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. RI Khan, Javed/P-9157-2014 OI Khan, Javed/0000-0002-5858-0488 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2005 VL 28 IS 6 BP 638 EP 639 DI 10.1097/01.cji.0000191032.15201.c1 PG 2 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 978WN UT WOS:000232903800108 ER PT J AU Khan, T Stauffer, JK Williams, R Hixon, JA Salcedo, R Lincoln, E Back, TC Lockett, S Sayers, TJ Wigginton, JM AF Khan, T Stauffer, JK Williams, R Hixon, JA Salcedo, R Lincoln, E Back, TC Lockett, S Sayers, TJ Wigginton, JM TI Proteasome inhibition upregulates the cell surface expression of receptors for IFN-gamma and TNF-alpha on murine neuroblastoma cells and enhances the proapoptotic and overall antitumor activity of systemic cytokine therapy in murine neuroblastoma tumors SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 20th Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY NOV 10-13, 2005 CL Alexandria, VA SP Int Soc Biol Therapy Canc C1 NCI, Frederick, MD 21701 USA. SAIC, Intramural Res Support Program, Frederick, MD USA. SAIC, Image Anal Lab, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2005 VL 28 IS 6 BP 640 EP 640 DI 10.1097/01.cji.0000191036.99953.19 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 978WN UT WOS:000232903800112 ER PT J AU Sayers, TJ Brooks, AD Ramirez, T Elliott, PJ Murphy, WJ AF Sayers, TJ Brooks, AD Ramirez, T Elliott, PJ Murphy, WJ TI The proteasome inhibitor bortezomib sensitizes human tumor cells to TRAIL-mediated apoptosis SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 20th Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY NOV 10-13, 2005 CL Alexandria, VA SP Int Soc Biol Therapy Canc C1 NCI, LEI, Frederick, MD 21701 USA. Univ Nevada, Reno, NV 89557 USA. Combinatorex, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2005 VL 28 IS 6 BP 641 EP 641 DI 10.1097/01.cji.0000191040.30448.8a PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 978WN UT WOS:000232903800116 ER PT J AU Shanker, A Brooks, AD Tristan, CA Sayers, TJ AF Shanker, A Brooks, AD Tristan, CA Sayers, TJ TI Tumor therapy with proteasome inhibitor bortezomib (Velcade, PS-341) plus death receptor (DR5) agonist antibody MD5.1 SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 20th Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY NOV 10-13, 2005 CL Alexandria, VA SP Int Soc Biol Therapy Canc C1 NCI, Basic Res Program, SAIC Frederick Inc, Frederick, MD 21701 USA. NCI, Expt Immunol Lab, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2005 VL 28 IS 6 BP 641 EP 641 DI 10.1097/01.cji.0000191041.30448.c3 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 978WN UT WOS:000232903800117 ER PT J AU Janik, JE O'Mahony, D Morris, JC Leslie, M O'Hagan, D Gao, W Stetler-Stevenson, MA Taylor, M Hammershaimb, L AF Janik, JE O'Mahony, D Morris, JC Leslie, M O'Hagan, D Gao, W Stetler-Stevenson, MA Taylor, M Hammershaimb, L TI Phase I trial of siplizumab in CD2-positive lymphoproliferative disease SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 20th Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY NOV 10-13, 2005 CL Alexandria, VA SP Int Soc Biol Therapy Canc C1 Medimmune Inc, Gaithersburg, MD 20878 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2005 VL 28 IS 6 BP 644 EP 644 DI 10.1097/01.cji.0000191049.06685.a4 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 978WN UT WOS:000232903800125 ER PT J AU Antony, PA Paulos, C Restifo, N AF Antony, PA Paulos, C Restifo, N TI IL-2 paradoxically controls tolerance and immunity to a tumor/self-antigen SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 20th Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY NOV 10-13, 2005 CL Alexandria, VA SP Int Soc Biol Therapy Canc C1 NCI, Surg Branch, Bethesda, MD 20892 USA. RI Restifo, Nicholas/A-5713-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2005 VL 28 IS 6 BP 647 EP 647 DI 10.1097/01.cji.0000191060.11630.7f PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 978WN UT WOS:000232903800136 ER PT J AU Beck, KE Blansfield, JA Tran, KQ Hughes, MS Royal, RE Kammula, US Topalian, SL Sherry, RM Rosenberg, SA Yang, JC AF Beck, KE Blansfield, JA Tran, KQ Hughes, MS Royal, RE Kammula, US Topalian, SL Sherry, RM Rosenberg, SA Yang, JC TI Enterocolitis in patients after antibody blockade of CTLA-4. SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 20th Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY NOV 10-13, 2005 CL Alexandria, VA SP Int Soc Biol Therapy Canc C1 NCI, Surg Branch, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2005 VL 28 IS 6 BP 647 EP 647 DI 10.1097/01.cji.0000191061.11630.36 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 978WN UT WOS:000232903800137 ER PT J AU Daar, ES Lynn, HS Donfield, SM Lail, A O'Brien, SJ Huang, W Winkler, CA AF Daar, ES Lynn, HS Donfield, SM Lail, A O'Brien, SJ Huang, W Winkler, CA CA Hemophila Growth Dev Study TI Stromal cell-derived factor-1 genotype, coreceptor tropism, and HIV type 1 disease progression SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; SYNCYTIUM-INDUCING PHENOTYPE; SDF-1 GENE POLYMORPHISMS; HIV-1-INFECTED INDIVIDUALS; AIDS PROGRESSION; PROGNOSTIC VALUE; CLINICAL-COURSE; T-LYMPHOCYTES; INFECTION; CCR5 AB This study used a well characterized cohort of human immunodeficiency virus type 1 (HIV-1)- infected hemophiliacs to define the relationship between the SDF1-3' A allele, the plasma HIV-1 coreceptor tropism, and the natural history of HIV-1 disease. Subjects heterozygous or homozygous for the SDF1-3' A allele experienced higher rates of decline in CD4(+) T cell counts over time than did those without the allele (P = .009). Moreover, they had an increased risk of progression to acquired immunodeficiency syndrome and death, a relationship that persisted even when baseline plasma HIV-1 RNA levels and CD4(+) T cell counts or CCR5D32 and CCR2-64I genotype were controlled for. This relationship was even stronger in a subgroup of subjects for whom tropism data were available. Subjects with the SDF1-3'A allele were also more likely to have detectable X4-tropic viruses (P = .012), and, when tropism was included in the survival analyses, the effect of the SDF1-3'A allele on disease progression was no longer significant. Therefore, the increased frequency of X4-tropic viruses in subjects carrying the SDF1-3' A allele may explain the observed adverse effect that this allele has on the natural history of HIV-1 disease. C1 Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Div HIV Med, Torrance, CA 90502 USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. ViroLog Inc, San Francisco, CA USA. Rho Inc, Chapel Hill, NC USA. NCI, Lab Genom Divers, Frederick, MD 21701 USA. NCI, Sci Applicat Int Corp, Frederick Canc Res & Dev Ctr, Frederick, MD 21701 USA. Chinese Univ Hong Kong, Sch Publ Hlth, Hong Kong, Hong Kong, Peoples R China. RP Daar, ES (reprint author), Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Div HIV Med, 1124 W Carson St,N-24, Torrance, CA 90502 USA. EM edaar@labiomed.org FU NCI NIH HHS [N01-CO-12400]; NIAID NIH HHS [AI27660, R44 AI048990, AI43638]; NICHD NIH HHS [HD41224] NR 40 TC 16 Z9 17 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD NOV 1 PY 2005 VL 192 IS 9 BP 1597 EP 1605 DI 10.1086/496893 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 970TR UT WOS:000232333000012 PM 16206074 ER PT J AU McKenzie, FE O'Meara, WP Wongsrichanalai, C AF McKenzie, FE O'Meara, WP Wongsrichanalai, C TI White blood cell counts in Plasmodium vivax malaria - Reply SO JOURNAL OF INFECTIOUS DISEASES LA English DT Letter C1 NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. US Naval Med Res Unit 2, Jakarta, Indonesia. RP McKenzie, FE (reprint author), NIH, Fogarty Int Ctr, Bldg 1, Bethesda, MD 20892 USA. NR 7 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 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD NOV 1 PY 2005 VL 192 IS 9 BP 1676 EP 1677 DI 10.1086/496995 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 970TR UT WOS:000232333000028 ER PT J AU Manca, C Tsenova, L Freeman, S Barczak, AK Tovey, M Murray, PJ Barry, C Kaplan, G AF Manca, C Tsenova, L Freeman, S Barczak, AK Tovey, M Murray, PJ Barry, C Kaplan, G TI Hypervirulent M-tuberculosis W/Beijing strains upregulate type IIFNs and increase expression of negative regulators of the Jak-Stat pathway SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH LA English DT Article ID INTERFERON-GAMMA; IFN-GAMMA; LISTERIA-MONOCYTOGENES; VIRAL-INFECTION; IN-VITRO; ALPHA/BETA; MACROPHAGES; MICE; RECEPTOR; CELLS AB The role of type I interferons (IFNs) in the host response to bacterial infections is controversial. Here, we examined the role of IFN-alpha/beta in the murine response to infection with Mycobacterium tuberculosis, using wildtype mice, mice with impaired signaling through the type I IFN receptor (IFNAR), and mice treated to reduce levels of type I IFNs. In this study, we used virulent clinical isolates of M. tuberculosis, including HN878, W4, and CDC1551. Our results indicate that higher levels of type I IFNs are induced by the HN878 and W4 strains. Induction of type I IFNs was associated with lower levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-12 (IL-12) and reduced T cell activation, and associated with decreased survival of the mice infected with HN878 or W4 relative to infection with CDC1551. Infection of mice with HN878 and W4 was also associated with relatively higher levels of mRNA for a number of negative regulators of the Jak-Stat signaling pathway, such as suppressors of cytokine signaling (SOCS) 1, 4, and 5, CD45, protein inhibitor of activated Stat1 (PIAS1), protein tyrosine phosphatase nonreceptor type 1 (Ptpn1), and protein tyrosine phosphatase nonreceptor type substrate 1 (Ptpns1). Taken together, these results suggest that increased type I IFNs may be deleterious for survival of M. tuberculosis-infected mice in association with reduced Th1 immunity. C1 Int Ctr Publ Hlth, Publ Hlth Res Inst, Lab Mycobacteriol Immun & Pathogenesis, Newark, NJ 07103 USA. NIAID, TB Res Sect, NIH, Rockville, MD 20852 USA. CNRS, Inst Andre Lwoff, UPR 9045, Lab Viral Oncol, F-94801 Villejuif, France. St Jude Childrens Res Hosp, Dept Infect Dis, Memphis, TN 38105 USA. RP Kaplan, G (reprint author), Int Ctr Publ Hlth, Publ Hlth Res Inst, Lab Mycobacteriol Immun & Pathogenesis, 225 Warren St, Newark, NJ 07103 USA. EM kaplan@phri.org RI Barry, III, Clifton/H-3839-2012 FU Intramural NIH HHS [Z01 AI000783-11]; NIAID NIH HHS [AI-22616, AI-54338, AI-54361, R01 AI080737] NR 37 TC 130 Z9 135 U1 1 U2 8 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1079-9907 J9 J INTERF CYTOK RES JI J. Interferon Cytokine Res. PD NOV PY 2005 VL 25 IS 11 BP 694 EP 701 DI 10.1089/jir.2005.25.694 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 993LR UT WOS:000233956100005 PM 16318583 ER PT J AU Ha, L Noonan, FP De Fabo, EC Merlino, G AF Ha, L Noonan, FP De Fabo, EC Merlino, G TI Animal models of melanoma SO JOURNAL OF INVESTIGATIVE DERMATOLOGY SYMPOSIUM PROCEEDINGS LA English DT Article; Proceedings Paper CT 53rd Annual Montagns Symposium on the Biology of Skin CY OCT 15-19, 2004 CL Gleneden Beach, OR SP Fdn Basic Cutaneous Res, Fujisawa Healthcare, Genetech, Natl Alopecia Areata Fdn, Oregon Hlth & Sci Univ Canc Inst, Orentreich Fdn Advancement Sci, Procter & Gamble Co, Stiefel Labs Inc, Taisho Pharmaceut Co Ltd, AmGen Med Educ Serv, Cascade Biolog Inc, Natl Psoriasis Fdn, John Wayne Canc Fdn, Novartis Pharmaceut Corp ID ULTRAVIOLET-RADIATION; MALIGNANT-MELANOMA; GROWTH-FACTOR; TUMORS C1 NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. George Washington Univ, Med Ctr, Sch Publ Hlth & Hlth Serv,Lab Pathobiol & Photoim, Dept Environm & Occupat Hlth, Washington, DC 20037 USA. RP Merlino, G (reprint author), NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. EM merlinog@mail.nih.gov NR 17 TC 6 Z9 7 U1 1 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1087-0024 J9 J INVEST DERM SYMP P JI J. Invest. Dermatol. Symp. Proc. PD NOV PY 2005 VL 10 IS 2 BP 86 EP 88 DI 10.1111/j.1087-0024.2005.200409.x PG 3 WC Dermatology SC Dermatology GA 982QF UT WOS:000233176000004 PM 16358815 ER PT J AU Suh, KS Mutoh, M Gerdes, M Yuspa, SH AF Suh, KS Mutoh, M Gerdes, M Yuspa, SH TI CLIC4, an intracellular chloride channel protein, is a novel molecular target for cancer therapy SO JOURNAL OF INVESTIGATIVE DERMATOLOGY SYMPOSIUM PROCEEDINGS LA English DT Article; Proceedings Paper CT 53rd Annual Montagns Symposium on the Biology of Skin CY OCT 15-19, 2004 CL Gleneden Beach, OR SP Fdn Basic Cutaneous Res, Fujisawa Healthcare, Genetech, Natl Alopecia Areata Fdn, Oregon Hlth & Sci Univ Canc Inst, Orentreich Fdn Advancement Sci, Procter & Gamble Co, Stiefel Labs Inc, Taisho Pharmaceut Co Ltd, AmGen Med Educ Serv, Cascade Biolog Inc, Natl Psoriasis Fdn, John Wayne Canc Fdn, Novartis Pharmaceut Corp DE chloride channel; stress; apoptosis; differentiation; cancer therapy ID P53; EXPRESSION; APOPTOSIS; GROWTH; FAMILY; CELLS; P64 AB Chloride intracellular channel (CLIC)4 is a p53- and tumor necrosis factor alpha (TNF alpha)-regulated chloride channel protein that is localized to the mitochondria and cytoplasm of mouse and human keratinocytes. CLIC4 protein increases in differentiating keratinocytes and in keratinocytes exposed to DNA-damaging agents and metabolic inhibitors. Increasing CLIC4 levels by transduction of recombinant CLIC4 causes apoptosis. CLIC4 translocates to the nucleus under a variety of conditions of cell stress, and nuclear CLIC4 is associated with cell cycle arrest and accelerated apoptosis. Reduction of CLIC4 and several other CLIC family members by expressing a doxycycline-regulated CLIC4 antisense also causes apoptosis in squamous cancer cell lines. Expressing antisense CLIC4 in tumors derived from transplanting these cells into nude mice inhibits tumor growth, increases tumor apoptosis, and reduces tumor cell proliferation. Co-administration of TNF alpha intraperitoneally enhances the tumor-inhibitory influence of CLIC4 antisense expression. Together, these results suggest that CLIC4 is important for keratinocyte viability and may be a novel target for anti-cancer therapy. C1 NCI, Cellular Carcinogenesis & Tumor Promot Lab, Canc Res Ctr, Bethesda, MD 20892 USA. RP Yuspa, SH (reprint author), NCI, Cellular Carcinogenesis & Tumor Promot Lab, Canc Res Ctr, Bldg 37,Room 4068,37 Convent Dr MSC-4255, Bethesda, MD 20892 USA. EM yuspa@mail.nih.gov NR 17 TC 31 Z9 36 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1087-0024 J9 J INVEST DERM SYMP P JI J. Invest. Dermatol. Symp. Proc. PD NOV PY 2005 VL 10 IS 2 BP 105 EP 109 DI 10.1111/j.1087-0024.2005.200402.x PG 5 WC Dermatology SC Dermatology GA 982QF UT WOS:000233176000007 PM 16358817 ER PT J AU Gareau, DS Lagowski, J Rossi, VM Viator, JA Merlino, G Kulesz-Martin, M Jacques, SL AF Gareau, DS Lagowski, J Rossi, VM Viator, JA Merlino, G Kulesz-Martin, M Jacques, SL TI Imaging melanoma in a murine model using reflectance-mode confocal scanning laser microscopy and polarized light imaging SO JOURNAL OF INVESTIGATIVE DERMATOLOGY SYMPOSIUM PROCEEDINGS LA English DT Article; Proceedings Paper CT 53rd Annual Montagns Symposium on the Biology of Skin CY OCT 15-19, 2004 CL Gleneden Beach, OR SP Fdn Basic Cutaneous Res, Fujisawa Healthcare, Genetech, Natl Alopecia Areata Fdn, Oregon Hlth & Sci Univ Canc Inst, Orentreich Fdn Advancement Sci, Procter & Gamble Co, Stiefel Labs Inc, Taisho Pharmaceut Co Ltd, AmGen Med Educ Serv, Cascade Biolog Inc, Natl Psoriasis Fdn, John Wayne Canc Fdn, Novartis Pharmaceut Corp DE confocal microscopy; diagnostic imaging; melanoma; mouse; polarization microscopy ID SKIN; CONTRAST AB The light-scattering properties of cutaneous tissues provide optical contrast for imaging the presence and depth of pigmented melanoma in a highly pigmented murine model, the C57/B6 mouse. Early lesions are difficult to identify when viewing black lesions on a black mouse. Two methods were used to image early lesions in this model. (1) A reflectance-mode confocal scanning laser microscope (rCSLM) was built to provide horizontal images (x-y at depth z) and transverse images (x-z at position y) non-invasively in the living mouse. (2) A polarized light imaging (PLI) camera was built using a linearly polarized white light source that viewed the skin through an analyzing linear polarizer oriented either parallel or perpendicular to the illumination's polarization to yield two images, "PAR" and "PER," respectively. The difference image, PAR-PER, eliminated multiply scattered light and yielded an image of the superficial but subsurface tissues based only on photons scattered once or a few times so as to retain their polarization. rCSLM could image melanoma lesions developing below the epidermis. PLI could distinguish superficial from deeper melanoma lesions because the melanin of the superficial lesions attenuated the PAR-PER image, whereas deeper lesions failed to attenuate the PAR-PER image. C1 Oregon Hlth Sci Univ, Dept Dermatol, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Dept Biomed Engn, Portland, OR 97239 USA. NCI, Mol Genet Sect, Mol Biol Lab, Bethesda, MD 20892 USA. RP Jacques, SL (reprint author), Oregon Hlth Sci Univ, Dept Dermatol, OP06,3181 SW Jackson Pk Rd, Portland, OR 97239 USA. EM sjacques@bme.ogi.edu FU NCI NIH HHS [CA98893, CA69533]; NIBIB NIH HHS [EB000224] NR 6 TC 4 Z9 4 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1087-0024 J9 J INVEST DERM SYMP P JI J. Invest. Dermatol. Symp. Proc. PD NOV PY 2005 VL 10 IS 2 BP 164 EP 169 DI 10.1111/j.1087-0024.2005.200408.x PG 6 WC Dermatology SC Dermatology GA 982QF UT WOS:000233176000014 PM 16363066 ER PT J AU Alving, B AF Alving, B TI Barbara Alving, MD SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Editorial Material AB Dr Barbara M. Alving is the acting director of the National Center for Research Resources (NCRR) at the National Institutes of Health (NIH) and the director of the Women's Health Initiative. She also is a professor of medicine at the Uniformed Services University of the Health Sciences in Bethesda, a master in the American College of Physicians, a former member of the Subcommittee on Hematology of the American Board of Internal Medicine, and a previous member of the US Food and Drug Administration's Blood Products Advisory Committee. Dr Alving earned her medical degree cum laude from Georgetown University School of Medicine, where she also completed an internship in internal medicine. She completed residency training in internal medicine and a fellowship in hematology at the Johns Hopkins University Hospital. During her career, she attained the rank of colonel in the US Army, serving as the chief of the Department of Hematology and director of the Division of Medicine at the Walter Reed Army Institute of Research. Subsequently, Dr Alving served as the director of the Medical Oncology/Hematology Section at Washington Hospital Center in Washington, DC. In 1999, Dr Alving joined the National Heart, Lung, and Blood Institute, where she served as the director of the extramural Division of Blood Diseases and Resources, deputy director of the Institute, and acting director In March 2005, she was appointed as NCRR's acting director. NCRR, in coordination with the other Institutes and Centers at the NIH, recently launched an initiative that is designed to transform the way in which clinical and translational research is conducted at academic health centers (AHCs) across the country. As part of the NIH Roadmap, this initiative is intended to advance the academic standing of clinical and translational science as a distinct discipline and to catalyze the development of an academic home for clinical and translational science. Dr Alving provided details on the initiative in a recent interview. C1 NIH, Natl Ctr Res Resources, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. Amer Coll Physicians, Philadelphia, PA 19106 USA. RP Alving, B (reprint author), NIH, Natl Ctr Res Resources, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD NOV PY 2005 VL 53 IS 7 BP 331 EP 333 PG 3 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 994VI UT WOS:000234058900001 PM 16297356 ER PT J AU Shetty, HU Chin, FT Musachio, JL Pike, VW AF Shetty, HU Chin, FT Musachio, JL Pike, VW TI Use of LC-MS-MS for the rapid, specific and sensitive quality control measurement of carrier in a PET radioligand: [F-18]FECNT SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Article DE LC-MS-MS; carrier; [F-18]FECNT; radioligand; PET ID POSITRON-EMISSION-TOMOGRAPHY; MASS-SPECTROMETRY; RADIOPHARMACEUTICALS AB In the production of radioligands for imaging low concentrations of target proteins (e.g. receptors or transporters) in human subjects with positron emission tomography, control of specific radioactivity is necessary for efficacy and safety. Such quality control requires a fast method to be available for measuring carrier (non-radioactive ligand) in each batch of radioligand, preceding its release for administration. Measurement is usually achieved with HPLC equipped with an ultraviolet (UV) absorbance detector. However, this method is not easily applicable to radioligands that have low UV extinction coefficients and are produced at high specific radioactivity, such as [F-18] (2 beta-carbomethoxy-3 beta-(4-chlorophenyl)-8-(2-fluoroethyl)nortropane; [F-18]FECNT). Here we describe a fast, specific and sensitive LC-MS-MS method for measuring carrier in [F-18]FECNT preparations. Small samples of formulated [F-18]FECNT plus an added internal standard (2 beta-carbomethoxy-3 beta-(4-chlorophenyl)-8-(n-propyl)nortropane; INTSTD) are rapidly eluted from a short reverse phase HPLC column into an MS probe. Following electrospray ionization, the molecular ions ([MH](+)) of FECNT (m/z = 326) and INTSTD (m/z = 322) are isolated and energized for collision-induced dissociation. The product ions from FECNT (m/z = 294) and INTSTD (m/z = 290) are monitored selectively. The calibration curve for MS response is linear for FECNT concentrations in the range 2-20 pg/mu l and suitable for reproducibly (RSD 5%) and rapidly (< 3 min) measuring low concentrations of carrier in [F-18]FECNT preparations. Copyright (c) 2005 John Wiley & Sons, Ltd. C1 NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. RP Shetty, HU (reprint author), NIMH, Mol Imaging Branch, NIH, Bldg 10,Rm B3 C351,MSC 1003,10 Ctr Dr, Bethesda, MD 20892 USA. EM shettyu@mail.nih.gov NR 12 TC 2 Z9 2 U1 2 U2 3 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PD NOV PY 2005 VL 48 IS 13 BP 929 EP 940 DI 10.1002/jlcr.1006 PG 12 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 991XF UT WOS:000233847300001 ER PT J AU Lu, SY Hong, J Musachio, JL Chin, FT Vermeulen, ES Wikstrom, HV Pike, VW AF Lu, SY Hong, J Musachio, JL Chin, FT Vermeulen, ES Wikstrom, HV Pike, VW TI Alternative methods for labeling the 5-HT1A receptor agonist, 1-[2-(4-fluorobenzoylamino)ethyl]-4-(7-methoxynaphthyl)piperazine (S14506), with carbon-11 or fluorine-18 SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Article DE agonist; carbon-11; fluorine-18; 5-HT1A; radioligand; microwave ID IN-VIVO EVALUATION; RADIOLIGAND; PET; BIODISTRIBUTION; RADIOTRACER; S-14506 AB 1-[2-(4-Fluorobenzoylamino)ethyl]-4-(7-methoxynaphthyl)piperazine (S14506) is one of the most potent and selective agonists at 5-HT1A receptors. For the purpose of prospective 5-HT1A receptor imaging with positron emission tomography and the investigation of radioligand metabolic pathways, S14506 was labeled with a positron emitter, either carbon-11 (t(1/2)=20.4min) or fluorine-18 (t(1/2)=109.7min), at different positions. Thus, [O-methyl-C-11]S14506 was obtained in a radiosynthesis time of 35min by treating O-desmethyl-S14506 with [C-11]iodomethane and tetrabutylammonium hydroxide in N,N-dimethylformamide. The overall decay-corrected radiochemical yield (RCY) of [O-methyl-C-11]S14506 ranged between 6 and 24% and the specific activity (SA) between 1343 and 3101 Ci/mmol (mean 2390; n=30). [carbonyl-C-11]S14506 was synthesized through a microwave-enhanced direct coupling of in situ generated [C-11]organocarboxymagnesium bromide with amine precursor. RCYs ranged from 10 to 18%. [F-18]S14506 was prepared via nucleophilic aromatic fluoridation of the 4-nitro analog in 14 35% RCY and with SA ranging from 1063 to 2302Ci/mmol (mean 1617; n=14) in a radiosynthesis time of 115min. Heating the radiofluoridation mixture for 5min at 180 degrees C in a single mode microwave cavity gave similar RCY and SA to heating for 30 min in an oil bath at the same temperature. Copyright (c) 2005 John Wiley & Sons, Ltd. C1 NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. Univ Groningen, Dept Med Chem, NL-9713 AV Groningen, Netherlands. RP Lu, SY (reprint author), NIMH, Mol Imaging Branch, NIH, Bldg 10,Room B3 C346,10 Ctr Dr, Bethesda, MD 20892 USA. EM Shuiyu.Lu@mail.nih.gov OI Lu, Shuiyu/0000-0003-0310-4318 NR 25 TC 6 Z9 7 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PD NOV PY 2005 VL 48 IS 13 BP 971 EP 981 DI 10.1002/jlcr.1009 PG 11 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 991XF UT WOS:000233847300004 ER PT J AU Mocellin, S Marincola, FM Young, HA AF Mocellin, S Marincola, FM Young, HA TI Interleukin-10 and the immune response against cancer: a counterpoint SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Review DE tumor-infiltrating macrophages; natural killer cell; tumor-associated antigen; tumor immunology; cytokine ID HUMAN DENDRITIC CELLS; NATURAL-KILLER-CELLS; REGULATORY T-CELLS; MEDIATED TUMOR REJECTION; HUMAN-MELANOMA CELLS; TOLL-LIKE RECEPTOR-2; METASTATIC MELANOMA; LUNG-CANCER; IN-VIVO; IL-10 PRODUCTION AB Although interleukin-10 (IL-10) is commonly regarded as an anti-inflammatory, immunosuppressive cytokine that favors tumor escape from immune surveillance, a wealth of evidence is accumulating that IL-10 also possesses some immunostimulating properties. In fact, IL-10 has the pleiotropic ability of influencing positively and negatively the function of innate and adaptive immunity in different experimental models, which makes it questionable to merely categorize this cytokine as a target of anti-immune escape therapeutic strategies or rather, as an immunological adjuvant in the fight against cancer. Here, we review available data about the immunostimulating anticancer properties of IL-10, and in particular, we focus on the hypothesis that in contrast to what occurs in secondary lymphoid organs, IL-10 overexpression within the tumor microenvironment may catalyze cancer immune rejection. C1 Univ Padua, Dept Oncol & Surg Sci, I-35128 Padua, Italy. Ctr Clin, Immunogenet Lab, Dept Transfus Med, NIH, Bethesda, MD USA. NCI, Canc Res Ctr, Expt Immunol Lab, Frederick, MD USA. RP Mocellin, S (reprint author), Univ Padua, Dept Oncol & Surg Sci, Via Giustiniani 2, I-35128 Padua, Italy. EM mocellins@hotmail.com NR 130 TC 204 Z9 217 U1 1 U2 10 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD NOV PY 2005 VL 78 IS 5 BP 1043 EP 1051 DI 10.1189/jib.0705358 PG 9 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 981NL UT WOS:000233095200002 PM 16204623 ER PT J AU Walsh, JD Kuszweski, J Wang, YX AF Walsh, JD Kuszweski, J Wang, YX TI Determining a helical protein structure using peptide pixels SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article DE RDC; periodicity; planarity; dipolar wave; Xplor-NIH ID RESIDUAL DIPOLAR COUPLINGS; NMR STRUCTURES; WAVES; ALIGNMENT; ACCURACY; MAPS AB The residual dipolar coupling-periodicity planarity correlation makes it possible to determine peptide plane orientations in regular periodic protein secondary structure elements. Each peptide plane orientation represents a "pixel" of protein structure, and is expressed in terms of three angles referred to as tilt, phase, and pitch angles. In this report, we present the novel "3P" (periodicity, planarity, and pixels) method that allows one to determine secondary and tertiary structure of alpha-helical proteins. We demonstrate the 3P method by determining the structure of domain 1 of the receptor-associated protein (RAP) to a backbone accuracy of 1.0 angstrom using RDCs measured in a single alignment medium, together with a minimal number of NOE distance restraints, using a new Xplor-NIH module. Published by Elsevier Inc. C1 NCI Frederick, Struct Biophys Lab, Prot Nucl Acid Interact Sect, NIH, Ft Detrick, MD 21702 USA. CIT, Div Computat Biol, Imaging Sci Lab, NIH, Bethesda, MD 20892 USA. RP Wang, YX (reprint author), NCI Frederick, Struct Biophys Lab, Prot Nucl Acid Interact Sect, NIH, Ft Detrick, MD 21702 USA. EM wangyu@ncifcrf.gov NR 25 TC 9 Z9 9 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 1090-7807 J9 J MAGN RESON JI J. Magn. Reson. PD NOV PY 2005 VL 177 IS 1 BP 155 EP 159 DI 10.1016/j.jmr.2005.06.014 PG 5 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA 974RU UT WOS:000232609900018 PM 16084744 ER PT J AU Kellman, P Chung, YC Simonetti, OP McVeigh, ER Arai, AE AF Kellman, P Chung, YC Simonetti, OP McVeigh, ER Arai, AE TI Multicontrast delayed enhancement provides improved contrast between myocardial infarction and blood pool SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE MRI; delayed enhancement; myocardial infarction; phase sensitive; inversion recovery; SENSE; parallel; MRI; T-2-weighted ID INVERSION-RECOVERY TRUEFISP; QUANTIFICATION; T-2; MRI AB Purpose: To develop and test a delayed-enhancement imaging method for improving the contrast between myocardial infarction (MI) and blood pool. Materials and Methods: The T-2 of blood is significantly longer than that of acute or chronic MI. The proposed multi-contrast delayed-enhancement (MCODE) imaging method produces a series of images with both T, and T2 weightings, which provides both excellent contrast between normal and infarcted myocardium. and between blood and MI. Results: The subendocardial border between MI and blood pool was easily discriminated in the T-2-weighted image. The measured MI-to-blood contrast-to-noise ratio (CNR) was better in the T2-weighted image than in the T-1-weighted image (22.5 +/- 8.7 vs. 2.9 +/- 3.1, mean +/- SD, N = 11, P < 0.001. for TrueFISP, and 19.4 +/- 10.8 vs. 3.9 +/- 2.3, N = 11, P < 0.001. for TurboFLASH). Conclusion: The MCODE method provides a significant improvement in the ability to easily discriminate subendocardial MI by providing a T-2-weighted image with high contrast between blood and MI. MCODE should improve both the detection and accurate sizing of MI. C1 NHLBI, Cardiac Energet Lab, NIH, DHHS, Bethesda, MD 20892 USA. Siemens Med Solut, Chicago, IL USA. Ohio State Univ, Columbus, OH 43210 USA. RP Kellman, P (reprint author), NHLBI, Cardiac Energet Lab, NIH, DHHS, 10 Ctr Dr,MSC-1061,Bldg 10,Room B1D416, Bethesda, MD 20892 USA. EM kellman@nih.gov RI Simonetti, Orlando/E-4098-2011; OI Chung, Yiu-Cho/0000-0003-1003-8320 FU Intramural NIH HHS [Z01 HL004608-08] NR 23 TC 25 Z9 25 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1053-1807 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD NOV PY 2005 VL 22 IS 5 BP 605 EP 613 DI 10.1002/jmri.20426 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 981NT UT WOS:000233096000003 PM 16215969 ER PT J AU Seltzer, JA Bachrach, CA Bianchi, SM Bledsoe, CH Casper, LM Chase-Lansdale, PL DiPrete, TA Hotz, VJ Morgan, SP Sanders, SG Thomas, D AF Seltzer, JA Bachrach, CA Bianchi, SM Bledsoe, CH Casper, LM Chase-Lansdale, PL DiPrete, TA Hotz, VJ Morgan, SP Sanders, SG Thomas, D TI Explaining family change and variation: Challenges for family demographers SO JOURNAL OF MARRIAGE AND FAMILY LA English DT Article DE children; family theory; fertility; intergenerational relationships; marriage; work and family ID MARITAL DISRUPTION; HOUSEHOLD LABOR; UNITED-STATES; CHILDREN; PARENTS; TIME; FERTILITY; MARRIAGE; BEHAVIOR; TRENDS AB Twenty years ago, the National Institute of Child Health and Human Development (NICHD) issued a request for proposals that resulted in the National Survey of Families and Households (NSFH), a unique survey valuable to a wide range of family scholars. This paper describes the efforts of an interdisciplinary group of family demographers to build on the progress enabled by the NSFH and many other theoretical and methodological innovations. Our work, also supported by NICHD, will develop plans for research and data collection to address the central question of what causes family change and variation. We outline the group's initial assessments of orienting frameworks, key aspects of family life to study, and theoretical and methodological challenges for research on family change. Finally, we invite family scholars to follow our progress and to help develop this shared public good. C1 Univ Calif Los Angeles, Dept Sociol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Calif State Populat Res, Los Angeles, CA 90095 USA. NICHHD, Demog & Behav Sci Branch, Bethesda, MD 20892 USA. Univ Maryland, Dept Sociol, College Pk, MD 20742 USA. Northwestern Univ, Dept Anthropol, Evanston, IL 60208 USA. Univ So Calif, Dept Sociol, Los Angeles, CA 90089 USA. Northwestern Univ, Inst Policy Res, Evanston, IL 60208 USA. Columbia Univ, Dept Sociol, New York, NY 10027 USA. Columbia Univ, Inst Social & Econ Res & Policy, New York, NY 10027 USA. Univ Calif Los Angeles, Dept Econ, Los Angeles, CA 90095 USA. Duke Univ, Dept Sociol, Durham, NC 27708 USA. Univ Maryland, Dept Econ, College Pk, MD 20742 USA. Univ Calif Los Angeles, Dept Econ, Los Angeles, CA 90095 USA. RP Seltzer, JA (reprint author), Univ Calif Los Angeles, Dept Sociol, 264 Haines Hall,375 Portola Plaza, Los Angeles, CA 90095 USA. EM seltzery@ucla.edu RI Brower, Susan/C-7090-2009 FU NICHD NIH HHS [R24 HD065563, N01 HD3, N01 HD3-3354, P2C HD065563] NR 94 TC 32 Z9 32 U1 1 U2 17 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-2445 J9 J MARRIAGE FAM JI J. Marriage Fam. PD NOV PY 2005 VL 67 IS 4 BP 908 EP 925 DI 10.1111/j.1741-3737.2005.00183.x PG 18 WC Family Studies; Sociology SC Family Studies; Sociology GA 974RI UT WOS:000232608700010 PM 20376277 ER PT J AU Murphy, CM Huestis, MA AF Murphy, CM Huestis, MA TI LC-ESI-MS/MS analysis for the quantification of morphine, codeine, morphine-3-beta-D-glucuronide, morphine-6-beta-D-glucuronide, and codeine-6-beta-D-glucuronide in human urine SO JOURNAL OF MASS SPECTROMETRY LA English DT Article DE morphine; codeine; glucuronide; electrospray ionization; tandem mass spectrometry ID CHROMATOGRAPHY-MASS-SPECTROMETRY; LIQUID-CHROMATOGRAPHY; BODY-FLUIDS; METABOLITES; HEROIN; MORPHINE-6-GLUCURONIDE; 6-MONOACETYLMORPHINE; COCAINE; HAIR AB A liquid chromatographic-electrospray ionization-tandem mass spectrometric method for the quantification of the opiates morphine, codeine, and their metabolites morphine-3-beta-D-glucuronide (M-3-G), morphine-6-p-beta-glucuronide (M-6-G) and codeine-6-beta-D-glucuronide (C-6-G) in human urine has been developed and validated. Identification and quantification were based on the following transitions: 286 to 201 and 229 for morphine, 300 to 215 and 243 for codeine, 644 to 468 for M-3-G, 462 to 286 for M-6-G, and 476 to 300 for C-6-G. Calibration by linear regression analysis utilized deuterated internal standards and a weighting factor of 1/X. The method was accurate and precise across a linear dynamic range of 25.0 to 4000.0 ng/ml. Pretreatment of urine specimens using solid phase extraction was sufficient to limit matrix suppression to less than 40% for all five analytes. The method proved to be suitable for the quantification of morphine, codeine, and their metabolites in urine specimens collected from opioid-dependent participants enrolled in a methadone maintenance program. Copyright (c) 2005 John Wiley & Sons, Ltd. C1 Natl Inst Drug Abuse, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Huestis, MA (reprint author), Natl Inst Drug Abuse, Intramural Res Program, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM mhuestis@intra.nida.nih.gov FU Intramural NIH HHS NR 11 TC 41 Z9 42 U1 3 U2 11 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1076-5174 J9 J MASS SPECTROM JI J. Mass Spectrom. PD NOV PY 2005 VL 40 IS 11 BP 1412 EP 1416 DI 10.1002/jms.921 PG 5 WC Biophysics; Chemistry, Organic; Spectroscopy SC Biophysics; Chemistry; Spectroscopy GA 986XG UT WOS:000233482400002 PM 16258895 ER PT J AU Karjala, Z Desch, CE Starost, MF AF Karjala, Z Desch, CE Starost, MF TI First description of a new species of Demodex (Acari : demodecidae) from rhesus monkey SO JOURNAL OF MEDICAL ENTOMOLOGY LA English DT Article DE Acari; Demodecidae; hair follicle mite; rhesus monkey; new species ID RE-EVALUATION; REDESCRIPTION; FOLLICULORUM AB Species of Demodex live in hair follicles and sebaceous glands of many species of mammals. Demodex macaci n sp. is described (all life stages) from a captive rhesus monkey, Macaca mulatta (Zimmermann, 1780). Mites were found at all levels of the hair follicles and occasionally in sebaceous glands of the skin of the perineal region. This is the first description of a demodectic hair follicle mite from the primate family Cercopithecidae. C1 NIH, Div Vet Resources, Bethesda, MD 20892 USA. Univ Connecticut, Dept Ecol & Evolutionary Biol, Hartford, CT 06117 USA. RP Karjala, Z (reprint author), NIH, Div Vet Resources, Bldg 28A, Bethesda, MD 20892 USA. NR 13 TC 6 Z9 6 U1 0 U2 4 PU ENTOMOLOGICAL SOCIETY AMERICA PI LANHAM PA 10001 DEREKWOOD LANE, STE 100, LANHAM, MD 20706-4876 USA SN 0022-2585 J9 J MED ENTOMOL JI J. Med. Entomol. PD NOV PY 2005 VL 42 IS 6 BP 948 EP 952 DI 10.1603/0022-2585(2005)042[0948:FDOANS]2.0.CO;2 PG 5 WC Entomology; Veterinary Sciences SC Entomology; Veterinary Sciences GA 983DJ UT WOS:000233211000005 PM 16465733 ER PT J AU Bauer, AJ Stratakis, CA AF Bauer, AJ Stratakis, CA TI The lentiginoses: cutaneous markers of systemic disease and a window to new aspects of tumourigenesis SO JOURNAL OF MEDICAL GENETICS LA English DT Review ID PROTEIN-KINASE-A; PEUTZ-JEGHERS-SYNDROME; GENOTYPE-PHENOTYPE ANALYSES; MESSENGER-RNA TRANSLATION; LHERMITTE-DUCLOS-DISEASE; BANNAYAN-ZONANA-SYNDROME; GERMLINE PTEN MUTATION; TUMOR-SUPPRESSOR GENE; SUBUNIT TYPE 1A; CARNEY-COMPLEX AB Familial lentiginosis syndromes cover a wide phenotypic spectrum ranging from a benign inherited predisposition to develop cutaneous lentigines unassociated with systemic disease, to associations with several syndromes carrying increased risk of formation of hamartomas, hyperplasias, and other neoplasms. The molecular pathways involved in the aetiology of these syndromes have recently been more clearly defined and several major cellular signalling pathways are probably involved: the protein kinase A (PKA) pathway in Carney complex (CNC), the Ras/Erk MAP kinase pathway in LEOPARD/Noonan syndromes, and the mammalian target of rapamycin pathway (mTOR) in Peutz-Jeghers syndrome and the diseases caused by PTEN mutations. Here we discuss the clinical presentation of these disorders and discuss the molecular mechanisms involved. The presence of lentigines in these diseases caused by diverse molecular defects is probably more than an associated clinical feature and likely reflects cross talk and convergence of signalling pathways of central importance to embryogenesis, neural crest differentiation, and end-organ growth and function of a broad range of tissues including those of the endocrine, reproductive, gastrointestinal, cardiac, and integument systems. C1 NICHD, Sect Endocrinol & Genet, DEB, NIH,CRC, Bethesda, MD 20892 USA. Walter Reed Army Med Ctr, Dept Pediat, Washington, DC 20307 USA. RP Stratakis, CA (reprint author), NICHD, Sect Endocrinol & Genet, DEB, NIH,CRC, Bldg 10,Room 1-3330,10 Ctr Dr,MSC 1103, Bethesda, MD 20892 USA. EM stratakc@mail.nih.gov NR 118 TC 28 Z9 30 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD NOV PY 2005 VL 42 IS 11 BP 801 EP 810 DI 10.1136/jmg.2003.017806 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 980XB UT WOS:000233050400001 PM 15958502 ER PT J AU Pittman, AM Myers, AJ Abou-Sleiman, P Fung, HC Kaleem, M Marlowe, L Duckworth, J Leung, D Williams, D Kilford, L Thomas, N Morris, CM Dickson, D Wood, NW Hardy, J Lees, AJ de Silva, R AF Pittman, AM Myers, AJ Abou-Sleiman, P Fung, HC Kaleem, M Marlowe, L Duckworth, J Leung, D Williams, D Kilford, L Thomas, N Morris, CM Dickson, D Wood, NW Hardy, J Lees, AJ de Silva, R TI Linkage disequilibrium fine mapping and haplotype association analysis of the tau gene in progressive supranuclear palsy and corticobasal degeneration SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID RICHARDSON-OLSZEWSKI-SYNDROME; PARKINSONS-DISEASE; DEMENTIA; SELECTION; FTDP-17; IDENTIFICATION; POLYMORPHISM; PHENOTYPE; MUTATION; MAPT AB Background: The haplotype H1 of the tau gene, MAPT, is highly associated with progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). Objective: To investigate the pathogenic basis of this association. Methods: Detailed linkage disequilibrium and common haplotype structure of MAPT were examined in 27 CEPH trios using validated HapMap genotype data for 24 single nucleotide polymorphisms (SNPs) spanning MAPT. Results: Multiple variants of the H1 haplotype were resolved, reflecting a far greater diversity of MAPT than can be explained by the H1 and H2 clades alone. Based on this, six haplotype tagging SNPs (htSNPs) that capture 95% of the common haplotype diversity were used to genotype well characterised PSP and CBD case-control cohorts. In addition to strong association with PSP and CBD of individual SNPs, two common haplotypes derived from these htSNPs were identified that are highly associated with PSP: the sole H2 derived haplotype was underrepresented and one of the common H1 derived haplotypes was highly associated, with a similar trend observed in CBD. There were powerful and highly significant associations with PSP and CBD of haplotypes formed by three H1 specific SNPs. This made it possible to define a candidate region of at least similar to 56 kb, spanning sequences from upstream of MAPT exon 1 to intron 9. On the H1 haplotype background, these could harbour the pathogenic variants. Conclusions: The findings support the pathological evidence that underlying variations in MAPT could contribute to disease pathogenesis by subtle effects on gene expression and/or splicing. They also form the basis for the investigation of the possible genetic role of MAPT in Parkinson's disease and other tauopathies, including Alzheimer's disease. C1 UCL, Reta Lila Weston Inst Neurol Studies, London W1T 4JF, England. Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England. NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. Inst Neurol, Sara Koe PSP Res Ctr, London WC1N 3BG, England. Newcastle Gen Hosp, Inst Ageing & Hlth, Newcastle Upon Tyne NE4 6BE, Tyne & Wear, England. Mayo Clin, Coll Med, Dept Neurosci, Jacksonville, FL 32224 USA. RP Lees, AJ (reprint author), UCL, Reta Lila Weston Inst Neurol Studies, London W1T 4JF, England. EM alees@ion.ucl.ac.uk RI de Silva, Rohan/C-1734-2008; Myers, Amanda/B-1796-2010; Hardy, John/C-2451-2009; Pittman, Alan/D-6231-2012; Lees, Andrew/A-6605-2009; Wood, Nicholas/C-2505-2009; Leung, Doris/R-5447-2016; OI de Silva, Rohan/0000-0002-5052-5775; Myers, Amanda/0000-0002-3100-9396; Wood, Nicholas/0000-0002-9500-3348; Leung, Doris/0000-0002-2558-7798; Dickson, Dennis W/0000-0001-7189-7917 FU Intramural NIH HHS; NIA NIH HHS [AG05128, P50 AG16570, P50-AG08671, U24 AG021886]; NIMH NIH HHS [MH60451]; NINDS NIH HHS [NS39764, P50-NS40256-06]; Parkinson's UK [G-4029] NR 36 TC 137 Z9 138 U1 0 U2 4 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD NOV PY 2005 VL 42 IS 11 BP 837 EP 846 DI 10.1136/jmg.2005.031377 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 980XB UT WOS:000233050400005 PM 15792962 ER PT J AU Ogino, S Wilson, RB Gold, B Flodman, P AF Ogino, S Wilson, RB Gold, B Flodman, P TI Bayesian risk assessment in genetic testing for autosomal dominant disorders with age-dependent penetrance, including hereditary cancer syndromes. SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Meeting Abstract CT Annual Meeting of the Association-for-Molecular-Pathology CY NOV 11-13, 2005 CL Scottsdale, AZ SP Assoc Mol Pathol C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Penn, Philadelphia, PA 19104 USA. Natl Canc Inst Frederick, Frederick, MD USA. Univ Calif Irvine, Irvine, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 1525-1578 J9 J MOL DIAGN JI J. Mol. Diagn. PD NOV PY 2005 VL 7 IS 5 BP 654 EP 655 PG 2 WC Pathology SC Pathology GA 978LA UT WOS:000232873500043 ER PT J AU Grigorenko, BL Nemukhin, AV Cachau, RE Topol, IA Burt, SK AF Grigorenko, BL Nemukhin, AV Cachau, RE Topol, IA Burt, SK TI Computational study of a transition state analog of phosphoryl transfer in the Ras-RasGAP complex: AlFx versus MgF3- SO JOURNAL OF MOLECULAR MODELING LA English DT Article DE GTP hydrolysis; transition state analog; QM/MM modeling ID MOLECULAR MECHANICAL METHOD; SIMULATIONS; SYSTEMS; FIELD; GTP AB The structures of the complexes between Ras.GDP bound to RasGAP in the presence of three probable g-phosphate analogs (AlF3433, AlF- and MgF-) for the transition state (TS) of the hydrolysis of guanosine triphosphate (GTP) by the Ras-RasGAP enzymes have been modeled by quantum mechanical-molecular mechanical (QM/MM) calculations. These simulations contribute to the dispute on the nature of the TS in the hydrolysis reaction, since medium resolution X-ray crystallography cannot discern among stereochemically similar isoelectronic species (e.g., AlF (or MgF)(-). The optimized geometry for each structure has been found starting from experimental coordinates of one of them (PDBID: 1WQ1). Direct comparison of the experimental and computed geometry configurations in the immediate vicinity of the active site suggests that MgF)(3)(3)- is the most likely candidate for the phosphate analog in the experimental structure. C1 Moscow MV Lomonosov State Univ, Dept Chem, Moscow 119992, Russia. NCI, SAIC Frederick, Adv Biomed Comp Ctr, Frederick, MD 21702 USA. RP Nemukhin, AV (reprint author), Moscow MV Lomonosov State Univ, Dept Chem, Moscow 119992, Russia. EM nemukhin@ncifcrf.gov RI Nemukhin, Alexander/P-9662-2015 FU NCI NIH HHS [N01-CO-12400] NR 23 TC 10 Z9 10 U1 0 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1610-2940 J9 J MOL MODEL JI J. Mol. Model. PD NOV PY 2005 VL 11 IS 6 BP 503 EP 508 DI 10.1007/s00894-005-0259-4 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Chemistry, Multidisciplinary; Computer Science, Interdisciplinary Applications SC Biochemistry & Molecular Biology; Biophysics; Chemistry; Computer Science GA 986XH UT WOS:000233482500008 PM 16052311 ER PT J AU Lim, SY Hoshiba, J Salem, N AF Lim, SY Hoshiba, J Salem, N TI An extraordinary degree of structural specificity is required in neural phospholipids for optimal brain function: n-6 docosapentaenoic acid substitution for docosahexaenoic acid leads to a loss in spatial task performance SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE artificial rearing; docosahexaenoic acid; docosapentaenoic acid; Morris water maze; n-3 essential fatty acid deficiency ID POLYUNSATURATED FATTY-ACIDS; ALPHA-LINOLENIC ACID; NEURONAL APOPTOSIS; LEARNING-ABILITY; DEFICIENT RATS; RHESUS-MONKEYS; WATER-MAZE; RETINA; MEMBRANES; LIPIDS AB This study was conducted to determine whether provision of preformed dietary docosapentaenoic acid (DPAn-6) can replace docosahexaenoic acid (DHA) for brain function as assessed by spatial task performance. A newly modified artificial rearing method was employed to generate n-3 fatty acid-deficient rats. Newborn pups were separated from their mothers at 2 days of age and given artificial rat milk containing linoleic acid (LA), or LA supplemented with 1% DHA (DHA), 1% DPAn-6 (DPA) or 1% DHA plus 0.4% DPAn-6 (DHA/DPA). The animals were then weaned onto similar pelleted diets. At adulthood, behavioural tasks were administered and then the brains were collected for fatty acid analysis. The LA and DPA groups showed a lower (63-65%) brain DHA than the dam-reared, DHA and DHA/DPA groups and this loss was largely compensated for by an increase in brain DPAn-6. The brain fatty acid composition in the DPA group was the same as that in the LA group at adulthood. In the Morris water maze, the LA and DPA groups exhibited a longer escape latency than the dam-reared and DHA groups and had a defect in spatial retention. In conclusion, DPAn-6 could not replace DHA for brain function, indicating a highly specific structural requirement for DHA. C1 Korea Maritime Univ, Div Marine Environm & Biosci, Pusan, South Korea. Okayama Univ, Dept Anim Resources, Adv Sci Res Ctr, Okayama, Japan. NIAAA, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD USA. RP 5625 Fishers Lane,Room 3N-07,MSC 9410, Bethesda, MD 20892 USA. EM nsalem@niaaa.nih.gov RI Wilkinson, Stuart/C-2802-2013 FU Intramural NIH HHS NR 44 TC 58 Z9 61 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3042 EI 1471-4159 J9 J NEUROCHEM JI J. Neurochem. PD NOV PY 2005 VL 95 IS 3 BP 848 EP 857 DI 10.1111/j.1471-4159.2005.03427.x PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 972ZZ UT WOS:000232493900022 PM 16135079 ER PT J AU Takase, H Yu, CR Liu, X Fujimoto, C Gery, I Egwuagu, CE AF Takase, H Yu, CR Liu, X Fujimoto, C Gery, I Egwuagu, CE TI Induction of suppressors of cytokine signaling (SOCS) in the retina during experimental autoimmune uveitis (EAU): Potential neuroprotective role of SOCS proteins SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE SOCS; EAU; uveitis; retina; autoimmune disease ID T-CELLS; LINEAGE COMMITMENT; NEGATIVE REGULATORS; MICE LACKING; TH2 CELLS; UVEORETINITIS; DISEASE; TRANSCRIPTION; EXPRESSION; RECEPTOR AB Suppressors of cytokine signaling (SOCS) are implicated in immunopathogenic mechanisms of autoimmune disease. We show here that SOCS expression in retina is temporarily correlated with progression of experimental autoimmune uveitis (EAU), an organ-specific autoimmune disease that serves as model of human uveitis. Peak of EAU correlates with highest SOCS genes expression while disease resolution coincides with their down-regulation. Surprisingly, SOCS5 is constitutively expressed in retina, SOCS5 expression increases significantly during EAU and remains elevated even after disease resolution. Our data suggest that cytokine-inducible SOCS members may be involved in negative regulation of inflammatory cytokines activities during EAU, while constitutively expressed SOCS5 may have neuroprotective functions. Published by Elsevier B.V. C1 NEI, Mol Immunol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. NEI, Expt Immunol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. Tokyo Med & Dent Univ, Grad Sch, Dept Ophthalmol & Visual Sci, Tokyo, Japan. RP Egwuagu, CE (reprint author), NEI, Mol Immunol Sect, Immunol Lab, NIH, Bldg 10,Room 10N116,10 Ctr Dr, Bethesda, MD 20892 USA. EM egwuaguc@nei.nih.gov NR 39 TC 25 Z9 27 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD NOV PY 2005 VL 168 IS 1-2 BP 118 EP 127 DI 10.1016/j.jneuroim.2005.07.021 PG 10 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 980ZB UT WOS:000233055600013 PM 16154209 ER PT J AU Zhu, PJ Stewart, RR McIntosh, JM Weight, FF AF Zhu, PJ Stewart, RR McIntosh, JM Weight, FF TI Activation of nicotinic acetylcholine receptors increases the frequency of spontaneous GABAergic IPSCs in rat basolateral amygdala neurons SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID MEDIAL HABENULA NEURONS; GATED ION CHANNELS; CHOLINERGIC PROJECTIONS; BASAL FOREBRAIN; SYNAPTIC TRANSMISSION; LATERAL NUCLEUS; GABA RELEASE; PHARMACOLOGICAL CHARACTERIZATION; HIPPOCAMPAL-NEURONS; SUBUNIT COMPOSITION AB The basolateral amygdala (BLA) is a critical component of the amygdaloid circuit, which is thought to be involved in fear conditioned responses. Using whole cell patch-clamp recording, we found that activation of nicotinic acetylcholine receptors (nAChRs) leads to an action potential-dependent increase in the frequency of spontaneous GABAergic currents in principal neurons in the BLA. These spontaneous GABAergic currents were abolished by a low-Ca2+/high-Mg2+ bathing solution, suggesting that they are spontaneous inhibitory postsynaptic currents (sIPSCs). Blockade of ionotropic glutamate receptors did not prevent this increased frequency of sIPSCs nor did blockade of alpha(7) nAChRs. Among the nAChR agonists tested, cystisine was more effective at increasing the frequency of the sIPSCs than nicotine or 1,1-dimethyl-4-phenyl piperazinium iodide, consistent with a major contribution of beta(4) nAChR subunits. The nicotinic antagonist, dihydro-beta-erythroidine, was less effective than d-tubocurarine in blocking the increased sIPSC frequency induced by ACh, suggesting that alpha(4)-containing nAChR subunits do not play a major role in the ACh-induced increased sIPSC frequency. Although alpha(2/3/4/7) and beta(2/4) nAChR subunits were found in the BLA by RT-PCR, the agonist and antagonist profiles suggest that the ACh-induced increase in sIPSC frequency involves predominantly alpha(3)beta(4)-containing nAChR subunits. Consistent with this, alpha-conotoxin-AuIB, a nAChR antagonist selective for the alpha(3)beta(4) subunit combination, inhibited the ACh-induced increase in the frequency of sIPSCs. The observations suggest that nicotinic activation increases the frequency of sIPSCs in the BLA by acting mainly on alpha(3)beta(4)-containing nicotinic receptors on GABAergic neurons and may play an important role in the modulation of synaptic transmission in the amygdala. C1 NIAAA, Mol & Cellular Neurobiol Lab, NIH, Bethesda, MD 20892 USA. NIAAA, Lab Integrat Neurosci, NIH, Bethesda, MD 20892 USA. Univ Utah, Dept Biol, Salt Lake City, UT 84112 USA. Univ Utah, Dept Psychiat, Salt Lake City, UT USA. RP Zhu, PJ (reprint author), NIAAA, Mol & Cellular Neurobiol Lab, NIH, 5625 Fishers Ln,Rm TS-28, Bethesda, MD 20892 USA. EM pzhu@mail.nih.gov FU Intramural NIH HHS; NIMH NIH HHS [MH-53631] NR 73 TC 25 Z9 26 U1 1 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD NOV PY 2005 VL 94 IS 5 BP 3081 EP 3091 DI 10.1152/jn.00974.2004 PG 11 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 973NF UT WOS:000232528900010 PM 16033935 ER PT J AU Berman, RA Heiser, LM Saunders, RC Colby, CL AF Berman, RA Heiser, LM Saunders, RC Colby, CL TI Dynamic circuitry for updating spatial representations. I. Behavioral evidence for interhemispheric transfer in the split-brain macaque SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID LATERAL INTRAPARIETAL AREA; SACCADIC EYE-MOVEMENTS; POSTERIOR PARIETAL CORTEX; CORPUS-CALLOSUM; RHESUS-MONKEY; SUPERIOR COLLICULUS; VISUAL SPACE; CEREBRAL COMMISSURES; COROLLARY DISCHARGE; ANTERIOR COMMISSURE AB Internal representations of the sensory world must be constantly adjusted to take movements into account. In the visual system, spatial updating provides a mechanism for maintaining a coherent map of salient locations as the eyes move. Little is known, however, about the pathways that produce updated spatial representations. In the present study, we asked whether direct cortico-cortical links are required for spatial updating. We addressed this question by investigating whether the forebrain commissures - the direct path between the two cortical hemispheres - are necessary for updating visual representations from one hemifield to the other. We assessed spatial updating in two split-brain monkeys using the double-step task, which involves saccades to two sequentially appearing targets. Accurate performance requires that the representation of the second target be updated to take the first saccade into account. We made two central discoveries regarding the pathways that underlie spatial updating. First, we found that split-brain monkeys exhibited a selective initial impairment on double-step sequences that required updating across visual hemifields. Second, and most surprisingly, these impairments were neither universal nor permanent: the monkeys were ultimately able to perform the across-hemifield sequences and, in some cases, this ability emerged rapidly. These findings indicate that direct cortical links provide the main substrate for updating visual representations, but they are not the sole substrate. Rather, a unified and stable representation of visual space is supported by a redundant cortico-subcortical network with a striking capacity for reorganization. C1 Mellon Inst 115, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Ctr Neural Basis Cognit, Pittsburgh, PA USA. NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA. Univ Pittsburgh, Dept Neurosci, Pittsburgh, PA USA. RP Colby, CL (reprint author), Mellon Inst 115, 4400 5th Ave, Pittsburgh, PA 15213 USA. EM ccolby@cnbc.cmu.edu FU NCRR NIH HHS [P41-RR-03631]; NEI NIH HHS [EY-12032] NR 74 TC 23 Z9 23 U1 1 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD NOV PY 2005 VL 94 IS 5 BP 3228 EP 3248 DI 10.1152/jn.00028.2005 PG 21 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 973NF UT WOS:000232528900024 PM 15888534 ER PT J AU Heiser, LM Berman, RA Saunders, RC Colby, CL AF Heiser, LM Berman, RA Saunders, RC Colby, CL TI Dynamic circuitry for updating spatial representations. II. Physiological evidence for interhemispheric transfer in area LIP of the split-brain macaque SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID LATERAL INTRAPARIETAL AREA; FRONTAL EYE FIELD; CORPUS-CALLOSUM; MONKEY; NEURONS; CORTEX; MEMORY; MAINTENANCE; ACTIVATION; ATTENTION AB With each eye movement, a new image impinges on the retina, yet we do not notice any shift in visual perception. This perceptual stability indicates that the brain must be able to update visual representations to take our eye movements into account. Neurons in the lateral intraparietal area ( LIP) update visual representations when the eyes move. The circuitry that supports these updated representations remains unknown, however. In this experiment, we asked whether the forebrain commissures are necessary for updating in area LIP when stimulus representations must be updated from one visual hemifield to the other. We addressed this question by recording from LIP neurons in split-brain monkeys during two conditions: stimulus traces were updated either across or within hemifields. Our expectation was that across-hemifield updating activity in LIP would be reduced or abolished after transection of the forebrain commissures. Our principal finding is that LIP neurons can update stimulus traces from one hemifield to the other even in the absence of the forebrain commissures. This finding provides the first evidence that representations in parietal cortex can be updated without the use of direct cortico-cortical links. The second main finding is that updating activity in LIP is modified in the split-brain monkey: across-hemifield signals are reduced in magnitude and delayed in onset compared with within-hemifield signals, which indicates that the pathways for across-hemifield updating are less effective in the absence of the forebrain commissures. Together these findings reveal a dynamic circuit that contributes to updating spatial representations. C1 Univ Pittsburgh, Dept Neurosci, Pittsburgh, PA USA. Univ Pittsburgh, Ctr Neural Basis Cognit, Pittsburgh, PA USA. NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA. RP Colby, CL (reprint author), 115 Mellon Inst, 4400 5th Ave, Pittsburgh, PA 15213 USA. EM ccolby@cnbc.cmu.edu FU NCRR NIH HHS [P41RR-03631]; NEI NIH HHS [EY-12032, EY-08908] NR 25 TC 27 Z9 27 U1 1 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD NOV PY 2005 VL 94 IS 5 BP 3249 EP 3258 DI 10.1152/jn.00029.2005 PG 10 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 973NF UT WOS:000232528900025 PM 15888533 ER PT J AU Moldakarimov, S Rollenhagen, JE Olson, CR Chow, CC AF Moldakarimov, S Rollenhagen, JE Olson, CR Chow, CC TI Competitive dynamics in cortical responses to visual stimuli SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID SHORT-TERM-MEMORY; BINOCULAR-RIVALRY; RELAY NEURONS; NEURAL THEORY; CORTEX; MACAQUE; VISION; MODEL; MECHANISMS; ATTENTION AB Neurons in the visual cortex of the macaque monkey exhibit a variety of competitive behaviors, including normalization and oscillation, when presented with multiple visual stimuli. Here we argue that a biophysically plausible cortical circuit with opponent inhibition, spike-frequency adaptation, and synaptic depression can account for the full range of behaviors. The governing parameter is the strength of inhibition between competing neuronal pools. As the strength of inhibition is increased, the pattern of network behavior shifts from normalization mode to oscillatory mode, with oscillations occurring at progressively lower frequency until, at the extreme, winner-take-all behavior appears. C1 Univ Pittsburgh, Dept Math, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Neurosci, Pittsburgh, PA 15260 USA. Ctr Neural Basis Cognit, Pittsburgh, PA USA. NIDDKD, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA. RP Chow, CC (reprint author), Univ Pittsburgh, Dept Math, Thackeray 505, Pittsburgh, PA 15260 USA. EM ccchow@pitt.edu RI Chow, Carson/A-7970-2009 FU NEI NIH HHS [R01 EY-11831]; NIMH NIH HHS [P50-MH-64445, K01 MH-01508] NR 30 TC 30 Z9 30 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD NOV PY 2005 VL 94 IS 5 BP 3388 EP 3396 DI 10.1152/jn.00159.2005 PG 9 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 973NF UT WOS:000232528900035 PM 15944239 ER PT J AU Grider, MH Mamounas, LA Le, W Shine, HD AF Grider, MH Mamounas, LA Le, W Shine, HD TI In situ expression of brain-derived neurotrophic factor or neurotrophin-3 promotes sprouting of cortical serotonergic axons following a neurotoxic lesion SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article ID INJURED SPINAL-CORD; NERVE GROWTH-FACTOR; RAT VISUAL-CORTEX; ADULT-RAT; TRANSPORTER; NEURONS; BDNF; PROJECTIONS; SURVIVAL; REGENERATION AB Neurotrophins promote sprouting and elongation of central nervous system (CNS) axons following injury. Consequently, it has been suggested that neurotrophins could be used to repair the CNS by inducing axonal sprouting from nearby intact axons, thereby compensating for the loss of recently injured axons. We tested whether long-term overexpression of neurotrophins in the rat cortex would induce sprouting of cortical serotonergic axons following a neurotoxic injury. After a single subcutaneous injection of para-chloroamphetamine (PCA; 9 mg/ml) that lesions the majority of serotonergic axons in the rat cortex, we injected adenoviral vectors containing cDNAs for brain-derived neurotrophic factor (Adv.BDNF), neurotrophin-3 (Adv.NT-3), or nerve growth factor (Adv.NGF) into the rat frontal cortex. Nine days later, we measured significant increases in the concentration of the respective neurotrophins surrounding the vector injection sites, as measured by ELISA. Immunohistochemical localization of serotonin revealed a fourfold increase in the density of serotonergic fibers surrounding the injection sites of Adv.BDNF and Adv.NT-3, corresponding to a 50% increase in cortical serotonin concentration, compared with a control vector containing the cDNA for enhanced green fluorescent protein (Adv.EGFP). In contrast, there was no difference in serotonergic fiber density or cortical serotonin concentration surrounding the injection of Adv.NGF compared with Adv.EGFR These data demonstrate that localized overexpression of BDNF or NT-3, but not NGF, is sufficient to promote sprouting of serotonergic axons in the cortex following an experimental neurotoxic injury. (c) 2005 Wiley-Liss, Inc. C1 Baylor Coll Med, Dept Neurosci, Houston, TX 77030 USA. Baylor Coll Med, Dept Cell & Gene Therapy, Houston, TX 77030 USA. NINDS, NIH, Bethesda, MD 20892 USA. Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. Baylor Coll Med, Dept Neurosurg, Houston, TX 77030 USA. Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. RP Shine, HD (reprint author), 1 Baylor Plaza,N1130, Houston, TX 77030 USA. EM hshine@bcm.tmc.edu FU NINDS NIH HHS [NS35280] NR 38 TC 25 Z9 25 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD NOV 1 PY 2005 VL 82 IS 3 BP 404 EP 412 DI 10.1002/jnr.20635 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 983GC UT WOS:000233218400011 PM 16206279 ER PT J AU Ammerman, JM Lonser, RR AF Ammerman, JM Lonser, RR TI Transtentorial approach - Response SO JOURNAL OF NEUROSURGERY LA English DT Editorial Material C1 George Washington Univ, Med Ctr, Washington, DC 20037 USA. NINDS, NIH, Bethesda, MD 20892 USA. RP Ammerman, JM (reprint author), George Washington Univ, Med Ctr, Washington, DC 20037 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD NOV PY 2005 VL 103 IS 5 BP 777 EP 777 PG 1 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 979GN UT WOS:000232930500004 ER PT J AU Ammerman, JM Lonser, RR Oldfield, EH AF Ammerman, JM Lonser, RR Oldfield, EH TI Posterior subtemporal transtentorial approach to intraparenchymal lesions of the anteromedial region of the superior cerebellum SO JOURNAL OF NEUROSURGERY LA English DT Article DE tumor; cerebellum; subtemporal approach; surgical technique; transtentorial approach ID LARGE BRIDGING VEINS; INFRATENTORIAL APPROACH; CEREBELLOPONTINE ANGLE; CLINICAL-EXPERIENCE; TECHNICAL NOTE; BRAIN-STEM; SKULL BASE; PRESERVATION; ANEURYSMS; RESECTION AB Object. To overcome the limitations associated with surgical approaches that have been described for accessing intraparenchymal lesions of the anteromedial region of the superior cerebellum, the authors used a posterior subtemporal transtentorial approach to remove tumors in this region. In this paper they describe the surgical technique that they used as well as the operative findings and clinical outcomes observed in patients who underwent resection of tumors in the anteromedial superior cerebellum. Methods. The consecutive patients with anteromedial superior cerebellar tumors who underwent resection performed using the posterior subtemporal transtentorial approach at the National Institutes of Health were included in this study. Clinical, neuroimaging, and operative results were analyzed. Three patients (two men and one woman) with anteromedial superior cerebellar tumors (two hemangioblastomas and one pilocytic astrocytoma) underwent resection via this approach. All the tumors were larger than 3 cm in diameter (range 3.1-3.5 cm). This approach provided excellent surgical access and permitted complete tumor resection in each case. The patients remained neurologically unchanged compared with preoperative baseline findings at the last follow-up examination (conducted at 4, 18, and 42 months postoperatively). One patient displayed a mild transient confusion immediately after surgery, but it resolved within 6 days. Conclusions. The posterior subtemporal transtentorial approach provides excellent access to the anteromedial superior cerebellar region. This approach permits resection of large lesions in this location, while avoiding many of the limitations associated with other approaches to this site. C1 NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. George Washington Univ, Med Ctr, Dept Neurol Surg, Washington, DC 20037 USA. RP Oldfield, EH (reprint author), NINDS, Surg Neurol Branch, NIH, 10 Ctr Dr,Bldg 10,Room 5D37, Bethesda, MD 20892 USA. EM eo10d@nih.gov NR 21 TC 7 Z9 8 U1 1 U2 1 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD NOV PY 2005 VL 103 IS 5 BP 783 EP 788 DI 10.3171/jns.2005.103.5.0783 PG 6 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 979GN UT WOS:000232930500006 PM 16304980 ER PT J AU Merrill, MJ Oldfield, EH AF Merrill, MJ Oldfield, EH TI A reassessment of vascular endothelial growth factor in central nervous system pathology SO JOURNAL OF NEUROSURGERY LA English DT Review DE blood-brain barrier; brain edema; brain injury; brain tumor; vascular permeability factor; vascular endothelial growth factor ID BLOOD-BRAIN-BARRIER; CEREBRAL ARTERIOVENOUS-MALFORMATIONS; VEGF MESSENGER-RNA; SPINAL-CORD-INJURY; INDUCED TRANSCRIPTIONAL ACTIVATION; INTERCELLULAR-ADHESION MOLECULE-1; RECEPTOR TYROSINE KINASE; FACTOR GENE-EXPRESSION; HIPPEL-LINDAU-DISEASE; ACIDIC PROTEIN GENE AB Overexpression of vascular endothelial growth factor (VEGF) is associated with several central nervous system (CNS) diseases and abnormalities, and is often postulated as a causative factor and promising therapeutic target in these settings. The authors' goal was to reassess the contribution of VEGF to the biology and pathology of the CNS. The authors review the literature relating to the following aspects of VEGF: 1) the biology of VEGF in normal brain; 2) the involvement of VEGF in CNS disorders other than tumors (traumatic and ischemic injuries, arteriovenous malformations, inflammation); and 3) the role of VEGF in brain tumor biology (gliomas and the associated vasogenic edema, and hemangioblastomas). The authors conclude the following: first, that VEGF overexpression contributes to the phenotype associated with many CNS disorders, but VEGF is a reactive rather than a causative factor in many cases; and second, that use of VEGF as a therapeutic agent or target is complicated by the effects of VEGF not only on the cerebral vasculature, but also on astrocytes, neurons, and inflammatory cells. In many cases, therapeutic interventions targeting the VEGF/VEGF receptor axis are likely to be ineffective or even detrimental. Clinical manipulation of VEGF levels in the CNS must be approached with caution. C1 NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Merrill, MJ (reprint author), NINDS, Surg Neurol Branch, NIH, Bldg 10,Room 5D-37, Bethesda, MD 20892 USA. EM merrillm@ninds.nih.gov NR 191 TC 27 Z9 28 U1 0 U2 1 PU AMER ASSOC NEUROLOGICAL SURGEONS PI CHARLOTTESVILLE PA UNIV VIRGINIA, 1224 WEST MAIN ST, STE 450, CHARLOTTESVILLE, VA 22903 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD NOV PY 2005 VL 103 IS 5 BP 853 EP 868 DI 10.3171/jns.2005.103.5.0853 PG 16 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 979GN UT WOS:000232930500016 PM 16304990 ER PT J AU Tipre, DN Goldstein, DS AF Tipre, DN Goldstein, DS TI Cardiac and extracardiac sympathetic denervation in Parkinson's disease with orthostatic hypotension and in pure autonomic failure SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE fluorodopamine; ammonia; pure autonomic failure; Parkinson's disease; PET ID MYOCARDIAL BLOOD-FLOW; N-13 AMMONIA; INNERVATION; HEART; 6-FLUORODOPAMINE; FATE AB The uptake of 6-F-18-fluorodopamine by cardiac noradrenergic nerves enables visualization of the sympathetic innervation of the left ventricular myocardium by PET. Patients with Parkinson's disease (PD) and orthostatic hypotension (OH) (PD+OH) or with pure autonomic failure (PAF) have markedly decreased myocardial 6-F-18-fluorodopamine-derived radioactivity, consistent with cardiac sympathetic denervation, a phenomenon that neurochemical, neuropharmacologic, and, most recently, postmortem neuropathologic studies have confirmed. In this study, we examined whether 6-18F-fluorodopamine can visualize sympathetic innervation in extracardiac organs and, if so, whether patients with PD+OH or PAF have neuroimaging evidence of extracardiac noradrenergic denervation. Methods: To validate the method, healthy volunteers underwent 6-18F-fluorodopamine scanning of the head, thorax, and abdomen, with or without treatment with desipramine to block sympathoneural uptake of catecholamines. N-13-Ammonia scanning was used to address possible group differences in 6-18Ffluorodopamine delivery by blood perfusion. Results: Desipramine treatment was associated with decreased 6-F-18-fluorodopamine-derived radioactivity in the heart, renal cortex, and thyroid gland but not in the liver, spleen, renal pelvis, or salivary glands. Both the PD+OH group and the PAF group had decreased 6-18F-fluorodopamine-derived radioactivity in the heart (P < 0.0001) and renal cortex (P = 0.02 and P = 0.005, respectively). The PD+OH group also had decreased radioactivity in the thyroid gland (P = 0.01). Neither group had decreased radioactivity in the other organs, after correction for N-13-ammonia-derived radioactivity. Conclusion: 6-F-18-Fluorodopamine scanning visualizes sympathetic innervation in the heart, renal cortex, and thyroid gland. Both PD+OH and PAF involve decreased noradrenergic innervation that is most prominent in the heart but is also detectable in extracardiac organs. C1 NINDS, Clin Neurocardiol Sect, NIH, Bethesda, MD 20892 USA. RP Tipre, DN (reprint author), Room 6N252,Bldg 10,10 Ctr Dr,MSC-1620, Bethesda, MD 20892 USA. EM dnyanesht@yahoo.com NR 21 TC 32 Z9 33 U1 0 U2 1 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD NOV PY 2005 VL 46 IS 11 BP 1775 EP 1781 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 981NR UT WOS:000233095800007 PM 16269589 ER PT J AU Gangloff, A Hsueh, WA Kesner, AL Kiesewetter, DO Pio, BS Pegram, MD Beryt, M Townsend, A Czernin, J Phelps, ME Silverman, DHS AF Gangloff, A Hsueh, WA Kesner, AL Kiesewetter, DO Pio, BS Pegram, MD Beryt, M Townsend, A Czernin, J Phelps, ME Silverman, DHS TI Estimation of paclitaxel biodistribution and uptake in human-derived xenografts in vivo with F-18-fluoropaclitaxel SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE breast cancer; paclitaxel; F-18; PET; microPET ID POSITRON-EMISSION-TOMOGRAPHY; ADVANCED BREAST-CANCER; MULTIDRUG-RESISTANCE; COLORECTAL-CARCINOMA; PREDICTIVE-VALUE; CHEMOTHERAPY; CELLS; TUMOR; TAXOL; MICE AB Paclitaxel (PAC) is widely used as a chemotherapy drug in the treatment of various malignancies, including breast, ovarian, and lung cancers. We examined the biodistribution of F-18-fluoropaclitaxel (F-18-FPAC) in mice with and without human breast cancer tumor xenografts by use of small-animal-dedicated PET (microPET) and clinically practical semiquantitative methods. We compared the PET data to data derived from direct harvesting and analysis of blood, organs, and breast carcinoma xenografts. Methods: PET data were acquired after tail vein injection of 18F-FPAC in nude mice. Tracer biodistribution in reconstructed images was quantified by region-of-interest analysis. Biodistribution also was assessed by harvesting and analysis of dissected organs, tumors, and blood after coadministration of F-18-FPAC and H-3-PAC. F-18 content in each tissue was assessed with a gamma-well counter, and H-3 content was quantified by scintillation counting of solubilized tissue after 18F radioactive decay. Results: The distributions of F-18-FPAC and H-3-PAC were very similar, with the highest concentrations in the small intestine, the lowest concentrations in the brain, and intermediate concentrations in tumor. Uptake in these and other tissues was not inhibited by the presence of more pharmacologic doses of unlabeled PAC. Administration of the P-glycoprotein modulator cyclosporine doubled the uptake of both F-18-FPAC and H-3-PAC into tumor. Conclusion: PET studies with F-18-FPAC can be used in conjunction with clinically practical quantification methods to yield estimates of PAC uptake in breast cancer tumors and normal organs noninvasively. C1 Univ Calif Los Angeles, Med Ctr, Nucl Med Clin,David Geffen Sch Med, Ahmanson Biol Imaging Div,Dept Mol & Med Pharmaco, Los Angeles, CA 90095 USA. NIH, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Dept Med, David Geffen Sch Med, Div Hematol & Oncol, Los Angeles, CA 90095 USA. RP Silverman, DHS (reprint author), Univ Calif Los Angeles, Med Ctr, Nucl Med Clin,David Geffen Sch Med, Ahmanson Biol Imaging Div,Dept Mol & Med Pharmaco, CHS AR 144,MC694215, Los Angeles, CA 90095 USA. EM dsilver@ucla.edu NR 29 TC 44 Z9 44 U1 1 U2 2 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD NOV PY 2005 VL 46 IS 11 BP 1866 EP 1871 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 981NR UT WOS:000233095800019 PM 16269601 ER PT J AU Cho, SY Ravasi, L Szajek, LP Seidel, J Green, MV Fine, HA Eckelman, WC AF Cho, SY Ravasi, L Szajek, LP Seidel, J Green, MV Fine, HA Eckelman, WC TI Evaluation of Br-76-FBAU as a PET reporter probe for HSV1-tk gene expression imaging using mouse models of human glioma SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE herpes simplex virus type 1 thymidine kinase; Br-76-FBAU; glioma; small-animal PET ID POSITRON-EMISSION-TOMOGRAPHY; THYMIDINE KINASE GENE; IN-VIVO; VITRO; PROLIFERATION; VALIDATION; VECTORS; ANIMALS; FIAU; FHPG AB The utility of 5-Br-76-bromo-2'-fluoro-2'-deoxyuridine (Br-76-FBAU), a uracil analog, as a PET reporter probe for use with the herpes simplex virus type 1 thymidine kinase (HSV1-tk) reporter gene system for gene expression imaging was evaluated in vivo and in vitro using human and rat glioma cells. Methods: Human glioma cell lines U87 and U251 were transcluced with replication-defective adenovirus constitutively expressing HSV1-tk (Ad.TK) or a control expressing green fluorescent protein (Ad.GFP). These cells were incubated with Br-76-FBAU for 20-120 min to determine the percentage of total dose uptake. In vitro uptake of equimolar concentrations (1.8 X 10(-8) mol/L) of Br-76-FBAU and 2'-fluoro-2'-deoxy-5-iodouracil-beta-(D)-arabino-furanoside (C-14-FIAU) was also determined in RG2-TK rat glioma cells stably expressing HSV1-tk and in control RG2 cells at 30-120 min. In vivo uptake of Br-76-FBAU was determined in subcutaneous U87 tumor intratumorally transduced with Ad.TK by ex vivo biodistribution. Uptake in intracranial U87 tumors transduced with Ad.TK expressing HSV1-tk was measured by brain autoradiography. In vivo PET was performed on subcutaneous and intracranial U87 tumors transcluced with Ad.TK and on subcutaneous and intracranial stably expressing RG2-TK tumors. Results: U87 and U251 cells transduced with Ad.TK had significantly increased uptake of Br-76-FBAU compared with cells transcluced with Ad.GFP over 20-120 min. In stably expressing cells at 120 min, 14C-FIAU uptake in RG2-TK tumor cells was 11.3 %ID (percentage injected dose) and in RG2 control cells was 1.7 %ID, and Br-76-FBAU uptake in RG2-TK tumor cells was 14.2 %ID and in RG2 control cells was 1.5 %ID. Ex vivo biodistribution of subcutaneous U87 tumors transduced with Ad.TK accumulated Br-76-FBAU significantly more than in the control Ad.GFP transduced tumor and normal tissue, with the lowest uptake in brain. Autoradiography showed localized uptake in intracranial U87 and U251 cells transduced with Ad.TK. PET image analyses of mice with RG2-TK tumors resulted in an increased tumor-to-background ratio of 13 and 26 from 2 to 6 h after injection, respectively, in intracranial tumors. Conclusion: (76) Er-FBAU accumulates in glioma cells constitutively expressing HSV1-tk by either adenoviral transduction or in stably expressing cell lines both in vitro and in Vivo. Br-76-FBAU shows promise as a PET reporter probe for use with the HSV1-tk in vivo gene expression imaging system. C1 NCI, Neurooncol Branch, NIH, Bethesda, MD 20892 USA. NINCDS, NIH, Bethesda, MD 20892 USA. NIH, PET Dept, Ctr Clin, Bethesda, MD 20892 USA. Univ Milan, Inst Radiol Sci, Milan, Italy. NIH, Dept Nucl Med, Ctr Clin, Bethesda, MD 20892 USA. RP Ravasi, L (reprint author), Natl Inst Biomed Imaging & Bioengn, PET Radiochem Grp, NIH, 10 Ctr Dr,Bldg 10,Room 1C401, Bethesda, MD 20982 USA. EM laura_ravasi@nih.gov NR 28 TC 16 Z9 16 U1 0 U2 0 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD NOV PY 2005 VL 46 IS 11 BP 1923 EP 1930 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 981NR UT WOS:000233095800026 PM 16269608 ER PT J AU Davis, CD Hord, NG AF Davis, CD Hord, NG TI Nutritional "Omics" technologies for elucidating the role(s) of bioactive food components in colon cancer prevention SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT Symposium on Nutrition Omics Technologies for Elucidating the Roles of Bioactive Food Conponents in Colon Cancer Prevention CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Soc Nutr Sci, Diet & Canc & Dietary Bioact Food Conponents Res Interest Sect DE nutrigenomics; nutrigenetics; epigenetics; proteomics; metabolomics ID DNA METHYLATION; METHYLENETETRAHYDROFOLATE REDUCTASE; VASCULAR-DISEASE; FOLATE; CARCINOGENESIS; CELLS; RISK; SUPPLEMENTS; EXPRESSION; NEOPLASIA AB Evidence continues to implicate dietary components and genetic susceptibilities as important determinants of cancer risk and tumor behavior. Variation in cancer incidence among and within populations with similar dietary patterns suggests that an individual's response may reflect interactions with genetic factors, which may modify gene, protein, and metabolite expression patterns. Nutrigenomics, defined as the interaction between nutrition and an individual's genome, will likely provide important clues about responders and norresponders. In this symposium, the role of bioactive food components in colon cancer susceptibility was used to exemplify the application of "omic" technologies for cancer prevention. Topics that were addressed included dietary changes and gene polymorphisms (nutrigenetics), DNA methylation (nutritional epigenomics), gene expression (nutritional transcriptomics), altered formation or bioactivation of proteins (proteomics), and characterizing how the quantity and timing of exposure influence small molecular weight cellular constituents (metabolomics). The final presentation focused on exfoliated cells as a surrogate sample for the evaluation of bioactive food components in cancer prevention. The goal of the symposium was to provide an example of each of the "omic" technologies as they relate to nutrition, cancer risk, and tumor behavior, and to help the participants understand that an integrated framework that simultaneously examines all of the "omic" technologies is needed. C1 NCI, Natl Inst Hlth, Nutr Sci Res Grp, Bethesda, MD 20892 USA. Michigan State Univ, Dept Food Sci & Human Nutr, E Lansing, MI 48824 USA. RP Davis, CD (reprint author), NCI, Natl Inst Hlth, Nutr Sci Res Grp, Bethesda, MD 20892 USA. EM davisci@mail.nih.gov NR 25 TC 27 Z9 32 U1 1 U2 7 PU AMER SOCIETY NUTRITIONAL SCIENCE PI BETHESDA PA 9650 ROCKVILLE PIKE, RM L-2407A, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD NOV PY 2005 VL 135 IS 11 BP 2694 EP 2697 PG 4 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 983VK UT WOS:000233260000034 PM 16251632 ER PT J AU Moser, RP Green, V Weber, D Doyle, C AF Moser, RP Green, V Weber, D Doyle, C TI Psychosocial, correlates of fruit and vegetable consumption among African American men SO JOURNAL OF NUTRITION EDUCATION AND BEHAVIOR LA English DT Article DE African Americans; eating behavior; fruit; male; vegetables ID CORONARY HEART-DISEASE; GENETIC TASTE MARKERS; US ADULTS; HEALTH; PREFERENCES; PREVENTION; CANCER; RISK; FOOD; ACCEPTANCE AB Objective: To determine the best predictors of fruit and vegetable consumption among African American men age 35 years and older. Design: Data (n = 291) from a 2001 nationally representative mail survey commissioned by the American Cancer Society. Participants: 291 African American men age 35 years and older Main Outcome Measures: Dependent variables: (1) total fruits and vegetables without fried potatoes, (2) total fruit with juice, and (3) total vegetables without fried potatoes. Independent variables included 3 blocks of predictors: (1) demographics, (2) a set of psychosocial scales, and (3) intent to change variables based on a theoretical algorithm. Analysis: Linear regression models; analysis of variance for the intent to change group. Alpha = .05. Results: Regression model for total fruits and vegetables, significant psychosocial predictors: social norms, benefits, tangible rewards, and barriers-other. Total fruit with juice: social norms, benefits, tangible rewards. Total vegetables, no fried potatoes: tangible rewards, barriers-other interests. fruit consumption appears to be motivated by perceived benefits and standards set by important people in their lives; vegetable consumption is a function of extrinsic rewards and preferences for high-calorie, fatty foods. The results suggest that communications to increase fruit and vegetable consumption should be crafted to reflect differences in sources of motivation for eating fruits versus eating vegetables. C1 NCI, Behav Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Sci Consulting Grp Inc, Natl Day Better Hlth Program 5 A, Washington, DC USA. Porter Novelli, Washington, DC USA. Amer Canc Soc, Atlanta, GA 30329 USA. RP Moser, RP (reprint author), NCI, Behav Res Program, Div Canc Control & Populat Sci, 6130 Execut Blvd,MSC 7326,Room 4052, Bethesda, MD 20892 USA. EM moserr@mail.nih.gov NR 59 TC 29 Z9 29 U1 3 U2 7 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1499-4046 J9 J NUTR EDUC BEHAV JI J. Nutr. Educ. Behav. PD NOV-DEC PY 2005 VL 37 IS 6 BP 306 EP 314 DI 10.1016/S1499-4046(06)60161-9 PG 9 WC Education, Scientific Disciplines; Nutrition & Dietetics SC Education & Educational Research; Nutrition & Dietetics GA 986XE UT WOS:000233482200006 PM 16242062 ER PT J AU Ali, AA Velasquez, MT Hansen, CT Mohamed, AI Bhathena, SJ AF Ali, AA Velasquez, MT Hansen, CT Mohamed, AI Bhathena, SJ TI Modulation of carbohydrate metabolism and peptide hormones by soybean isoflavones and probiotics in obesity and diabetes SO JOURNAL OF NUTRITIONAL BIOCHEMISTRY LA English DT Article DE metabolism; soybean; isoflavone; probiotics; peptide hormones; obesity; diabetes ID POLYCYSTIC KIDNEY-DISEASE; DIETARY SOY PROTEIN; CARDIOVASCULAR RISK-FACTORS; URIC-ACID CONCENTRATION; LACTOBACILLUS-ACIDOPHILUS; POSTMENOPAUSAL WOMEN; ANIMAL-MODEL; SERUM-LIPIDS; INSULIN-RESISTANCE; PURIFIED DIETS AB Soybean and its isoflavones have been shown to have beneficial effects on carbohydrate and lipid metabolism and on renal function. Probiotics may potentiate the beneficial effects of isoflavones by converting the inactive isoflavone glycoside to aglycones, which are biologically active, thereby producing a synergistic effect. We therefore studied the effects of soybean isoflavones in the presence and absence of probiotics on glucose and triglyceride metabolism and the peptide hormones involved in their metabolism. Lean and obese SHR/N-cp rats were fed AIN-93 diets containing 0.1% soybean isoflavone mixture, 0.1% probiotics mixture or both. Plasma was analyzed for glucose, triglycerides, parameters of renal function and peptide hormones-insulin, leptin, glucagon and ACTH-that are involved in glucose and lipid metabolism. Isoflavones given alone lowered plasma glucose in both phenotypes while triglyceride was decreased only in lean animals. Isoflavones also lowered aspartate amino transferase and alanine amino transferase in both phenotypes. Isoflavones had significant effect on plasma insulin, leptin and glucagon in lean rats but not in obese rats. Thus, our data show that in lean animals, isoflavones have hypoglycemic and hypolipidemic effect, and the effect is mediated by changes in peptide hormones. When lipid levels are very high as in obese rats, isoflavones fail to lower plasma triglyceride levels. Probiotics do not appear to enhance the effect of isoflavones. (c) 2005 Elsevier Inc. All rights reserved. C1 USDA, Beltsville Human Nutr Res Ctr, Phytonutrients Lab, ARS, Beltsville, MD 20705 USA. George Washington Univ, Med Ctr, Dept Med, Washington, DC 20037 USA. NIH, Rockville, MD 20850 USA. Virginia State Univ, Petersburg, VA 23806 USA. RP Bhathena, SJ (reprint author), USDA, Beltsville Human Nutr Res Ctr, Phytonutrients Lab, ARS, Beltsville, MD 20705 USA. EM bhathens@ba.ars.usda.gov NR 71 TC 41 Z9 42 U1 1 U2 22 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0955-2863 J9 J NUTR BIOCHEM JI J. Nutr. Biochem. PD NOV PY 2005 VL 16 IS 11 BP 693 EP 699 DI 10.1016/j.jnutbio.2005.03.011 PG 7 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA 984LN UT WOS:000233306500007 PM 16081264 ER PT J AU Chen, AM Rogan, WJ AF Chen, AM Rogan, WJ TI Improving behavior of lead-exposed children: Micronutrient supplementation, chelation, or prevention SO JOURNAL OF PEDIATRICS LA English DT Editorial Material ID ENVIRONMENTAL LEAD; SCHOOL ENTRY; BLOOD LEAD; THERAPY; IQ C1 NIEHS, Epidemiol Branch, Dept Hlth & Human Serv, NIH, Res Triangle Pk, NC 27709 USA. RP Rogan, WJ (reprint author), NIEHS, Epidemiol Branch, Dept Hlth & Human Serv, NIH, MD A3-05,POB 12233, Res Triangle Pk, NC 27709 USA. EM rogan@niehs.nih.gov RI Rogan, Walter/I-6034-2012 OI Rogan, Walter/0000-0002-9302-0160 NR 14 TC 2 Z9 2 U1 3 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD NOV PY 2005 VL 147 IS 5 BP 570 EP 571 DI 10.1016/j.jpeds.2005.08.044 PG 2 WC Pediatrics SC Pediatrics GA 987EA UT WOS:000233500000005 PM 16291342 ER PT J AU Wendler, D Emanuel, EJ AF Wendler, D Emanuel, EJ TI What is a "minor" increase over minimal risk? SO JOURNAL OF PEDIATRICS LA English DT Editorial Material ID CHILDREN C1 NIH, Dept Clin Bioeth, Ctr Clin, Bethesda, MD 20892 USA. RP Wendler, D (reprint author), NIH, Dept Clin Bioeth, Ctr Clin, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM dwendler@nih.gov NR 9 TC 14 Z9 14 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD NOV PY 2005 VL 147 IS 5 BP 575 EP 578 DI 10.1016/j.jpeds.2005.07.013 PG 4 WC Pediatrics SC Pediatrics GA 987EA UT WOS:000233500000007 PM 16291344 ER PT J AU Nikiforovich, GV Mihalik, B Catt, KJ Marshall, GR AF Nikiforovich, GV Mihalik, B Catt, KJ Marshall, GR TI Molecular mechanisms of constitutive activity: mutations at position 111 of the angiotensin AT(1) receptor SO JOURNAL OF PEPTIDE RESEARCH LA English DT Article DE angiotensin; angiotensin type 1 receptor; constitutively active mutants; molecular modeling ID ANGIOTENSIN-II RECEPTOR; PROTEIN-COUPLED RECEPTORS; 3RD TRANSMEMBRANE DOMAIN; AT(1) RECEPTOR; TYPE-1 RECEPTOR; LIGAND-BINDING; CONFORMATIONAL-CHANGES; ASPARAGINE RESIDUES; ADRENERGIC-RECEPTOR; RHODOPSIN STRUCTURE AB A possible molecular mechanism for the constitutive activity of mutants of the angiotensin type 1 receptor (AT(1)) at position 111 was suggested by molecular modeling. This involves a cascade of conformational changes in spatial positions of side chains along transmembrane helix (TM3) from L112 to Y113 to F117, which in turn, results in conformational changes in TM4 (residues I152 and M155) leading to the movement of TM4 as a whole. The mechanism is consistent with the available data of site-directed mutagenesis, as well as with correct predictions of constitutive activity of mutants L112F and L112C. It was also predicted that the double mutant N111G/L112A might possess basal constitutive activity comparable with that of the N111G mutant, whereas the double mutants N111G/Y113A, N111G/F117A, and N111G/I152A would have lower levels of basal activity. Experimental studies of the above double mutants showed significant constitutive activity of N111G/L112A and N111G/F117A. The basal activity of N111G/I152A was higher than expected, and that of N111G/Y113A was not determined due to poor expression of the mutant. The proposed mechanism of constitutive activity of the AT(1) receptor reveals a novel nonsimplistic view on the general problem of constitutive activity, and clearly demonstrates the inherent complexity of the process of G protein-coupled receptor (GPCR) activation. C1 Washington Univ, Sch Med, Dept Biochem & Mol Biophys, St Louis, MO 63110 USA. NICHHD, Endocrinol & Reprod Res Branch, Bethesda, MD 20892 USA. RP Nikiforovich, GV (reprint author), Washington Univ, Sch Med, Dept Biochem & Mol Biophys, St Louis, MO 63110 USA. EM gregory@ccb.wustl.edu OI Marshall, Garland/0000-0002-3098-0332 FU NIGMS NIH HHS [GM 53630] NR 77 TC 21 Z9 21 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1397-002X J9 J PEPT RES JI J. Pept. Res. PD NOV PY 2005 VL 66 IS 5 BP 236 EP 248 DI 10.1111/j.1399-3011.2005.00293.x PG 13 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 973AB UT WOS:000232494100004 PM 16218991 ER PT J AU Mager, DE Shirey, JD Cox, D Fitzgerald, DJ Abernethy, DR AF Mager, DE Shirey, JD Cox, D Fitzgerald, DJ Abernethy, DR TI Mapping the dose-effect relationship of orbofiban from sparse data with an artificial neural network SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE orbofiban; pharmacodynamics; neural networks; dose-response; mathematical model; population pharmacodynamics; humans ID CHRONIC-RENAL-FAILURE; PHARMACODYNAMICS; ABCIXIMAB; VARIABILITY; ANGIOPLASTY; ANTAGONIST AB A neural network (NN) pharmacodynamic model was developed that correlates the inhibition of ex vivo platelet aggregation by orbofiban, an oral glycoprotein IIb/IIIa antagonist, with the administered dose and patient characteristics. Data were obtained from a Phase-II dose-finding study of orbofiban in patients presenting with acute coronary syndromes. A back-propagation NN was designed to predict drug effect measured at predose and 4 and 6 h on treatment days 1, 28, and 84 (nine responses/ patient). The training set consisted of patients for whom complete response profiles were reported (n = 67), and remaining patients were included in the validation data set (n = 47). The concentration-effect relationship was described additionally using a population direct-effect inhibitory sigmoidal model, and a comparison of the predictive performances of both models was performed. The final NN reasonably described orbofiban pharmacodynamics from sparse data sets without specifying a structural model or drug concentrations. Despite considerable inter-patient variability in response-time profiles, the population model revealed a strong correlation between drug concentration and effect and exhibited greater precision than the NN model. Although the population model showed greater precision, these results suggest that NNs may be useful for individualizing pharmacotherapy when drug concentrations are relatively unpredictable or unavailable. (c) 2005 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 94:2475-2486, 2005. C1 NIA, Ctr Gerontol Res, Clin Invest Lab, Baltimore, MD 21224 USA. Royal Coll Surg, Dept Clin Pharmacol, Dublin, Ireland. Univ Coll Dublin, Dublin, Ireland. RP Abernethy, DR (reprint author), NIA, Ctr Gerontol Res, Clin Invest Lab, Baltimore, MD 21224 USA. EM abernethyd@grc.nia.nih.gov RI Cox, Dermot/A-8465-2008 OI Cox, Dermot/0000-0003-1365-3396 NR 21 TC 6 Z9 7 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0022-3549 J9 J PHARM SCI-US JI J. Pharm. Sci. PD NOV PY 2005 VL 94 IS 11 BP 2475 EP 2486 DI 10.1002/jps.20384 PG 12 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 980PH UT WOS:000233030000011 PM 16200613 ER PT J AU Campbell, VC Kopajtic, TA Newman, AH Katz, JL AF Campbell, VC Kopajtic, TA Newman, AH Katz, JL TI Assessment of the influence of histaminergic actions on cocaine-like effects of 3 alpha-diphenylmethoxytropane analogs SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID DOPAMINE UPTAKE INHIBITORS; H-1 ANTAGONISTS; SQUIRREL-MONKEY; MOUSE-BRAIN; TRANSPORTER; BENZTROPINE; BINDING; METHAMPHETAMINE; LIGANDS; BEHAVIOR AB Previous studies demonstrated that analogs of benztropine (BZT) possess high affinity for the dopamine (DA) transporter (DAT) but generally have behavioral effects different from those of cocaine, suggesting either unique actions at the DA transporter or that another action of these drugs interferes with cocaine-like effects. Because the parent compound has histamineantagonistic effects, the affinity of its analogs for histamine H-1, H-2, and H-3 receptors were compared with DA transporter affinity to assess whether those differences predicted the amount of cocaine-like activity. All of the compounds displaced [H-3] mepyramine from H-1, [I-125] iodoaminopotentidine from H-2, and [H-3]N-alpha-methylhistamine from H-3 histamine receptors with affinities ranging from 15.7 to 37,600, 218 to > 4430, and 4040 to > 150,000 nM, respectively. Affinities at histamine H-1 receptors were, respectively, approximately 25- or 300-fold greater than those at H-2 or H-3 histamine receptors. Relative affinities for H-1 and DAT binding did not reliably predict the degree of cocaine-like stimulation of locomotor activity. In addition, interactions of various histaminic agents with cocaine assessed whether an action at any of the histamine sites could interfere with cocaine-like effects. None of the histaminic agents fully substituted for cocaine in rats trained to discriminate 10 mg/kg cocaine from saline nor did any of the compounds antagonize or otherwise diminish the discriminative stimulus effects of cocaine. The results suggest that affinity for histamine receptors cannot account for the diminished cocainelike effects of the BZT analogs and suggest alternatively that these compounds have actions different from those of cocaine but likely mediated by their interaction with the DAT. C1 NIDA, Intramural Res Program, Psychobiol Sect, NIH, Baltimore, MD 21224 USA. NIDA, Intramural Res Program, Med Chem Sect, NIH, Baltimore, MD 21224 USA. RP Katz, JL (reprint author), NIDA, Intramural Res Program, Psychobiol Sect, NIH, POB 5180, Baltimore, MD 21224 USA. EM jkatz@intra.nida.nih.gov NR 27 TC 23 Z9 23 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD NOV PY 2005 VL 315 IS 2 BP 631 EP 640 DI 10.1124/jpet.105.090829 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 975SD UT WOS:000232681300019 PM 16055673 ER PT J AU Rodd, ZA Bell, RL McQueen, VK Davids, MR Hsu, CC Murphy, JM Li, TK Lumeng, L McBride, WJ AF Rodd, ZA Bell, RL McQueen, VK Davids, MR Hsu, CC Murphy, JM Li, TK Lumeng, L McBride, WJ TI Prolonged increase in the sensitivity of the posterior ventral tegmental area to the reinforcing effects of ethanol following repeated exposure to cycles of ethanol access and deprivation SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID ALCOHOL-PREFERRING RATS; DOPAMINERGIC-NEURONS; WISTAR RATS; NUCLEUS-ACCUMBENS; P RATS; REGIONAL HETEROGENEITY; RECEPTOR ANTAGONISTS; INVOLVEMENT; EXCITATION; AUTORECEPTORS AB The posterior ventral tegmental area (VTA) is a neuroanatomical substrate mediating the reinforcing effects of ethanol in rats. Repeated alcohol deprivations produce robust ethanol intakes of alcohol-preferring (P) rats during relapse and increase the reinforcing effects of oral alcohol self-administration. The objective of this study was to test the hypothesis that alcohol drinking and repeated alcohol deprivations will increase the reinforcing effects of ethanol within the posterior VTA of P rats. Groups of female P rats were used (alcohol-naive, continuous access, and repeatedly deprived). Each rat was implanted with a guide cannula aimed at the posterior VTA. Depression of the active lever produced the infusion of 100 nl of artificial cerebrospinal fluid (CSF) or ethanol (25-300 mg%). Each rat was given only one ethanol concentration during the 4-h sessions conducted every other day. Compared with the infusions of artificial CSF, the alcohol-naive group reliably self-infused 75 and 150 mg% ethanol, but not the lower or higher concentrations. On the other hand, the continuous access group had significantly higher self-infusions of 50, 75, 150, and 300 mg% ethanol compared with artificial CSF infusions. The repeatedly deprived group also self-infused significantly more of 50, 75, 150, and 300 mg% ethanol than artificial CSF; moreover, the number of infusions for all four concentrations was higher in the repeatedly deprived versus the continuous access group. Chronic alcohol drinking by P rats increased the reinforcing effects of ethanol within the posterior VTA, and repeated alcohol deprivations produced a further increase in these reinforcing effects of ethanol. C1 Indiana Univ, Sch Med, Inst Psychiat Res, Dept Psychiat, Indianapolis, IN 46202 USA. Indiana Univ, Sch Med, Dept Biochem, Indianapolis, IN 46202 USA. Indiana Univ, Sch Med, Dept Med, Indianapolis, IN 46202 USA. Indiana Univ Purdue Univ, Dept Psychol, Purdue Sch Sci, Indianapolis, IN 46202 USA. NIAAA, Bethesda, MD USA. RP Rodd, ZA (reprint author), Indiana Univ, Sch Med, Inst Psychiat Res, Dept Psychiat, 791 Union Dr, Indianapolis, IN 46202 USA. EM zrodd@iupui.edu RI Rodd, Zachary/L-1580-2015 OI Rodd, Zachary/0000-0002-8105-1920 FU NIAAA NIH HHS [AA11261, AA07611, AA12262, AA13522, P50 AA007611, R01 AA011261, R01 AA012262, R01 AA012262-06A2, U01 AA013522, U24 AA013522] NR 33 TC 33 Z9 33 U1 1 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD NOV PY 2005 VL 315 IS 2 BP 648 EP 657 DI 10.1124/jpet.105084350 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 975SD UT WOS:000232681300021 PM 16076936 ER PT J AU Bottone, FG Moon, Y Alston-Mills, B Eling, TE AF Bottone, FG Moon, Y Alston-Mills, B Eling, TE TI Transcriptional regulation of activating transcription factor 3 involves the early growth response-1 gene SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; BETA SUPERFAMILY MEMBER; CYCLOOXYGENASE INHIBITORS; ATF3 GENE; ENDOTHELIAL-CELLS; SULINDAC SULFIDE; CARCINOMA CELLS; REPRESSOR ATF3; TARGET GENES; C-JUN AB Previously, our laboratory identified activating transcription factor 3 (ATF3) as up-regulated by nonsteroidal anti- inflammatory drugs using microarray analysis of mRNA from human colorectal cancer cells treated with sulindac sulfide. ATF3 is a transcription factor involved in cell growth, apoptosis, and invasion and is induced by a variety of anticancer and dietary compounds. However, the regulation of ATF3 by anticancer agents is not known. The promoter of ATF3 contains several transcription factor binding sites. We identified three putative Egr-1 binding sites in the promoter of ATF3 and report for the first time that the molecular mechanism responsible for the transcriptional regulation of ATF3 by two divergent pharmaceutical compounds, sulindac sulfide and troglitazone, involved the early growth response gene-1 (Egr-1). For example, overexpression of Egr-1 protein induced ATF3 mRNA 3.5-fold and transcriptional activity of an ATF3 promoter construct more than 20-fold. ATF3 and Egr-1 mRNA and protein and ATF3 promoter activity were induced by these compounds, whereas induction of ATF3 by these compounds was blocked by Egr-1 small interfering RNA. Sulindac sulfide and troglitazone regulated ATF3 promoter activity, which was suppressed when the two Egr-1 sites were mutated. These compounds induced phosphorylation of extracellular signal-regulated kinase1/2 (Erk1/2), whereas a dominant-negative inhibitor of mitogenactivate protein kinase kinase (MEK)1 blocked the induction of ATF3. The MEK1/2 inhibitor PD98059 (2'-amino-3'-methoxyflavone) blocked the induction of ATF3 and Egr-1 mRNA expression and ATF3 promoter activity by these compounds. Therefore, this is a novel first report demonstrating that the expression of ATF3 occurs via Egr-1 downstream of Erk1/2. C1 NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. N Carolina State Univ, Dept Anim Sci, Raleigh, NC 27695 USA. RP Eling, TE (reprint author), POB 12233,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM eling@niehs.nih.gov NR 30 TC 31 Z9 32 U1 0 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD NOV PY 2005 VL 315 IS 2 BP 668 EP 677 DI 10.1124/jpet.089607 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 975SD UT WOS:000232681300023 PM 16079301 ER PT J AU Moon, Y Glasgow, WC Eling, TE AF Moon, Y Glasgow, WC Eling, TE TI Curcumin suppresses interleukin 1 beta-mediated microsomal prostaglandin E synthase 1 by altering early growth response gene 1 and other signaling pathways SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID TRANSCRIPTION FACTOR EGR-1; NF-KAPPA-B; CHEMOPREVENTIVE AGENT CURCUMIN; PHORBOL ESTER; SYNOVIAL FIBROBLASTS; GASTRIC-CANCER; E-2 PRODUCTION; PPAR-GAMMA; IN-VIVO; EXPRESSION AB Curcumin (diferuloylmethane) is one of the phytophenolic compounds found in the turmeric plant with anti-inflammatory and anticarcinogenic activities. One possible mechanism for these activities is the inhibition of prostaglandin ( PG) E 2 formation. In this study and other reports, curcumin suppresses interleukin-1 beta - induced formation of prostaglandin E-2 in a concentration-dependent manner. Interleukin-1 beta-induced microsomal prosta-glandin E synthase 1 (mPGES-1) and cyclooxygenase-2 were attenuated by curcumin at the protein and mRNA levels, but a more dramatic inhibition of mPGES-1 expression was observed at lower concentrations of curcumin in A549 human lung epithelial cells. The inhibition of mPGES-1 expression by curcumin shifted the arachidonic acid profile from PGE(2) to PGF(2 alpha) and 6-keto-PGF(1 alpha) as major metabolites. The expression of early growth response gene 1 (EGR- 1), a key transcription factor of cytokine-induced mPGES-1, was inhibited by curcumin. Incubation with siRNA for EGR-1 inhibited interleukin (IL)-1 beta-induced mPGES-1, and the controlled expression of EGR-1 increased the mPGES-1 expression. Several proinflammatory signaling molecules, such as nuclear factor kappa B (NF-kappa B) and mitogen-activated protein kinases, are also known to affect curcumin-regulated gene expression. Curcumin inhibited I kappa B kappa phosphorylation and degradation and thus reduced the expression of mPGES-1. Curcumin suppressed cytokine-induced mPGES-1 by inhibiting phosphorylation of Jun N-terminal kinase (JNK)1/2. However, EGR-1 expression was suppressed by lower concentrations of curcumin, as compared with JNK1/2 and I kappa B alpha. These results indicate that curcumin inhibits IL-1 beta-induced PGE(2) formation by inhibiting the expression of mPGES-1 that is mediated by suppression of EGR-1 expression as well as NF-kappa B and JNK1/2. C1 NIEHS, Mol Carcinogenesis Lab, Eicosanoid Biochem Sect, NIH, Res Triangle Pk, NC 27709 USA. Mercer Univ, Sch Med, Macon, GA 31207 USA. RP Eling, TE (reprint author), NIEHS, Mol Carcinogenesis Lab, Eicosanoid Biochem Sect, NIH, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM eling@niehs.nih.gov FU Intramural NIH HHS NR 35 TC 33 Z9 34 U1 0 U2 3 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD NOV PY 2005 VL 315 IS 2 BP 788 EP 795 DI 10.1124/jpet.105.084434 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 975SD UT WOS:000232681300036 PM 16081677 ER PT J AU Jia, L Coward, L Gorman, GS Noker, PE Tomaszewski, JE AF Jia, L Coward, L Gorman, GS Noker, PE Tomaszewski, JE TI Pharmacoproteomic effects of isoniazid, ethambutol, and N-geranyl-N '-(2-adamantyl)ethane-1,2-diamine (SQ109) on Mycobacterium tuberculosis H37Rv SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID DRUG DISCOVERY; 2-DIMENSIONAL ELECTROPHORESIS; PROTEOMICS; PROTEINS; GENE; IDENTIFICATION; TECHNOLOGY; EXPRESSION; SEQUENCE; CLONING AB The present study was aimed at fingerprinting pharmacoproteomic alterations of the Mycobacterium tuberculosis H37Rv strain induced by antitubercular drugs isoniazid (INH), ethambutol (EMB), and SQ109 [N-geranyl-N'-(2-adamantyl)ethane-1,2-diamine, a novel 1,2-diamine-based EMB analog], providing new understanding of pharmacoproteomic mechanisms of each and exploring new drug targets. The three drugs produced significant down-regulation of 13 proteins, including immunogenic ModD, Mpt64, with proteins from the Pro-Glu family being inhibited the most. Alternatively, the three drugs up-regulated 17 proteins, including secreted antigenic proteins ESAT-6 and CFP-10. Among these, ESAT-6 and AphC were most affected by INH, whereas EMB had the greatest effect on ESAT-6. All three drugs produced only moderate up-regulation of aerobic and iron metabolism proteins, i.e., electron transfer flavoprotein Fix A and Fix B, and ferritin-like protein BfrB, suggesting that the interruption of microbacterial energy metabolism is not a primary mechanism of action. INH suppressed ATP-dependent DNA/RNA helicase, but up-regulated beta-keto-acyl-acyl carrier protein synthase. These effects may contribute to its bactericidal effects. In contrast, EMB and SQ109 did just the opposite: these drugs up-regulated the helicase and down-regulated the synthase. For most of the H37Rv proteins, similar pharmacoproteomic patterns were found for both EMB and SQ109. None of the drugs significantly regulated expression of chaperonins GroES, GroEL2, and Dnak, suggesting that these drugs do not affect chaperone-mediated nascent polypeptide folding and sorting. The present study identified proteins directly modulated by the actions of INH, EMB, and SQ109 and distinguished INH activity from the diamine antitubercular compounds that inhibit M. tuberculosis H37Rv. C1 NCI, Dev Therapeut Program, NIH, Rockville, MD 20852 USA. So Res Inst, Birmingham, AL 35255 USA. RP Jia, L (reprint author), NCI, Dev Therapeut Program, NIH, Rm 8042,6130 Execut Blvd, Rockville, MD 20852 USA. EM jiale@mail.nih.gov FU NCI NIH HHS [N01-CM-52203, N01-CM-07110] NR 29 TC 31 Z9 34 U1 1 U2 7 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD NOV PY 2005 VL 315 IS 2 BP 905 EP 911 DI 10.1124/jpet.105.087817 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 975SD UT WOS:000232681300049 PM 16085758 ER PT J AU Notenboom, S Miller, DS Kuik, LH Smits, P Russel, FGM Masereeuw, R AF Notenboom, S Miller, DS Kuik, LH Smits, P Russel, FGM Masereeuw, R TI Short-term exposure of renal proximal tubules to gentamicin increases long-term multidrug resistance protein 2 (Abcc2) transport function and reduces nephrotoxicant sensitivity SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID ORGANIC ANION SECRETION; CONJUGATE EXPORT PUMP; PREGNANE-X RECEPTOR; CONSTITUTIVE-ANDROSTANE RECEPTOR; DRUG-METABOLIZING-ENZYMES; NUCLEAR RECEPTORS; MRP2 GENE; MECHANISMS; EXPRESSION; EFFLUX AB We previously showed that the function of renal multidrug resistance protein (Mrp) 2 (Abcc2) is reduced by endothelin (ET)-1 signaling through an ETB receptor, nitric-oxide synthase (NOS), cGMP, and protein kinase C and that this pathway was activated by several nephrotoxicants (Masereeuw et al., 2000; Terlouw et al., 2001; Notenboom et al., 2002, 2004). Here, we determined the long-term effects on Mrp2-mediated transport (luminal fluorescein methotrexate accumulation) of short-term (30 min) exposure to ET-1 and the aminoglycoside antibiotic, gentamicin. Our data show that over the 3 h following exposure, proximal tubules recovered fully from the initial decrease in Mrp2-mediated transport and that transport activity was not changed 9 h later. However, 24 h after exposure, luminal accumulation of an Mrp2 substrate had increased by 50%. Increased transport at 24 h was accompanied by an increased transporter protein content of the luminal plasma membrane as measured by immunostaining. Blocking ET-1 signaling at the ETB receptor or downstream at NOS or guanylyl cyclase abolished both stimulation of transport and increased transporter expression. Thus, regardless of whether signaling was initiated by a short exposure to ET-1 or to a nephrotoxicant, the time course of Mrp2 response to ETB signaling was the same and was multiphasic. Finally, when tubules were exposed to gentamicin for 30 min and removed to gentamicin-free medium for 24 h, they were less sensitive to acute gentamicin toxicity than paired controls not initially exposed to the drug. Thus, short-term exposure to ET-1 or gentamicin resulted in long-term protection against a second insult. C1 Radbound Univ Nijmegen, Med Ctr, Dept Pharmacol & Toxicol, Nijmegen Ctr Mol Life Sci 233, NL-6500 HB Nijmegen, Netherlands. Natl Inst Environm Hlth Sci, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC USA. Mt Desert Isl Biol Lab, Salsbury Cove, ME USA. RP Masereeuw, R (reprint author), Radbound Univ Nijmegen, Med Ctr, Dept Pharmacol & Toxicol, Nijmegen Ctr Mol Life Sci 233, POB 9101, NL-6500 HB Nijmegen, Netherlands. EM r.masereeuw@ncmls.ru.nl RI Russel, Frans/B-3184-2014; Masereeuw, Roos/N-3582-2014; Smits, P.A.B.M./E-2889-2015; OI Russel, Frans/0000-0002-7959-2314; Masereeuw, Rosalinde/0000-0002-1560-1074 NR 40 TC 15 Z9 15 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD NOV PY 2005 VL 315 IS 2 BP 912 EP 920 DI 10.1124/jpet.105.089094 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 975SD UT WOS:000232681300050 PM 16085757 ER PT J AU Klein, RC Yakel, JL AF Klein, RC Yakel, JL TI Paired-pulse potentiation of alpha 7-containing nAChRs in rat hippocampal CA1 stratum radiatum interneurones SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID NICOTINIC ACETYLCHOLINE-RECEPTORS; LONG-TERM POTENTIATION; INTRACELLULAR CALCIUM; SYNAPTIC-TRANSMISSION; CHROMAFFIN CELLS; AXON TERMINALS; DESENSITIZATION; NEURONS; CHANNEL; ALPHA-7 AB Diverse subtypes of nicotinic acetylcholine receptors (nAChRs), including fast-desensitizing alpha 7-containing receptors, are expressed in the CNS. While nAChRs appear to regulate cognitive processing and synaptic plasticity, little is known to date about how this regulation occurs, particularly in brain regions known to be important for cognition. By combining patch-clamp electrophysiology with local photolysis of caged carbachol to rapidly activate the alpha 7-containing nAChRs in rat hippocampal CA1 stratum radiatum interneurones in slices, we describe a novel transient up-regulation of channel function. The nAChRs were activated using a paired-pulse uncaging protocol, where the duration of the UV laser pulses (5-25 ms) and the interval between pulses (200 ins to 30 s) were varied. At relatively long interpulse intervals, we observed a strong (> 75%) decrease in the amplitude of the second response due to desensitization. However, when two pulses were applied at a 200 ms interval, a > 3-fold increase in the amplitude of the second response was observed, a phenomenon referred to here as paired-pulse potentiation. Interestingly, this potentiation appeared to be regulated by [Ca2+](i), and/or Ca2+-dependent processes, as it was significantly enhanced by dialysing cells with either the Ca2+ chelator BAPTA, or with peptide inhibitors of either calcineurin or PKC, and was attenuated by dialysing cells with the CaMKII inhibitor KN-93. No potentiation was observed using caged GABA or glutamate, indicating some specificity for nAChRs. Thus, rat hippocampal alpha 7-containing nAChRs possess a newly described phenomenon of paired-pulse potentiation that may be involved in regulating synaptic plasticity in the hippocampus. C1 NIEHS, Neurobiol Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA. RP Yakel, JL (reprint author), NIEHS, Neurobiol Lab, NIH, DHHS, POB 12233,F2-08,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM yakel@niehs.nih.gov FU Intramural NIH HHS NR 32 TC 20 Z9 20 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD NOV 1 PY 2005 VL 568 IS 3 BP 881 EP 889 DI 10.1113/jphysiol.2005.096081 PG 9 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 983EI UT WOS:000233213500013 PM 16141265 ER PT J AU Jackson, SN Wang, HYJ Woods, AS AF Jackson, SN Wang, HYJ Woods, AS TI Study of the fragmentation patterns of the phosphate-arginine noncovalent bond SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE phosphate-arginine interaction; receptor heteromerization; gas phase stability; fragmentation pathways; noncovalent complexes ID IONIZATION MASS-SPECTROMETRY; RECEPTOR HETEROMERIZATION; ELECTROSTATIC INTERACTION; COMPLEXES; PHOSPHOPEPTIDES; BINDING; MALDI AB Our previous work has highlighted the role of certain amino acid residues, mainly two or more adjacent arginine on one peptide and two or more adjacent glutamate, or aspartate, or a phosphorylated residue on the other in the formation of noncovalent complexes (NCX) between peptides. In the present study, we employ ESI-MS to investigate the gas-phase stability and dissociation pathways of the NCX of a basic peptide VLRRRRKRVN, an epitope from the third intracellular loop of the dopamine D-2 receptor, with the phosphopetide SVSTDpTpSAE, an epitope from the cannabinoid CB1 carboxyl terminus. ESI-MS/MS analysis of the NCX between VLRRRRKRVN and SVSTDpTpSAE suggests two dissociation pathways for the NCX. The major pathway is the disruption of the electrostatic interactions between the Arg residues and the phosphate groups, while an alternative pathway is also recorded, in which the complex is dissociated along the covalent bond between the oxygen from either Thr or Ser and HPO3. To verify the alternative pathway, we have used an ion trap instrument to conduct MS3 analysis on the product ions of both dissociation pathways. C1 NIDA, IRP, NIH, Baltimore, MD 21224 USA. RP Woods, AS (reprint author), NIDA, IRP, NIH, 5500 Nathan Schock Dr, Baltimore, MD 21224 USA. EM awoods@intra.nida.nih.gov FU Intramural NIH HHS NR 15 TC 31 Z9 31 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1535-3893 J9 J PROTEOME RES JI J. Proteome Res. PD NOV-DEC PY 2005 VL 4 IS 6 BP 2360 EP 2363 DI 10.1021/pr050261d PG 4 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 994CH UT WOS:000234007200053 PM 16335986 ER PT J AU Frontera, WR Fuhrer, MJ Jette, AM Chan, L Cooper, RA Duncan, PW Kemp, JD Ottenbacher, KJ Peckham, PH Roth, EJ Tate, DG AF Frontera, WR Fuhrer, MJ Jette, AM Chan, L Cooper, RA Duncan, PW Kemp, JD Ottenbacher, KJ Peckham, PH Roth, EJ Tate, DG TI Rehabilitation medicine summit: Building research capacity - Executive summary SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Editorial Material C1 Harvard Univ, Sch Med, Spaulding Rehabil Hosp, Boston, MA 02114 USA. NIH, Bethesda, MD 20892 USA. Boston Univ, Boston, MA 02215 USA. Univ Washington, Seattle, WA 98195 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. Univ Florida, Gainesville, FL 32611 USA. Powers Pyles Sutter & Verville PC, Washington, DC USA. Univ Texas, Med Branch, Galveston, TX 77555 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Rehabil Inst Chicago, Chicago, IL 60611 USA. Univ Michigan, Ann Arbor, MI 48109 USA. RP Frontera, WR (reprint author), Harvard Univ, Sch Med, Spaulding Rehabil Hosp, 125 Nashua St, Boston, MA 02114 USA. EM wfrontera@partners.org OI Jette, Alan/0000-0002-2117-9973 NR 3 TC 0 Z9 0 U1 0 U2 0 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PD NOV-DEC PY 2005 VL 42 IS 6 BP XI EP XXIV DI 10.1682/JRRD.2005.12.0179 PG 14 WC Rehabilitation SC Rehabilitation GA 047MQ UT WOS:000237883800001 ER PT J AU Hill, JM Syed, MA Arai, AE Powell, TM Paul, JD Zalos, G Read, EJ Khuu, HM Leitman, SF Horne, M Csako, G Dunbar, CE Waclawiw, MA Cannon, RO AF Hill, JM Syed, MA Arai, AE Powell, TM Paul, JD Zalos, G Read, EJ Khuu, HM Leitman, SF Horne, M Csako, G Dunbar, CE Waclawiw, MA Cannon, RO TI Outcomes and risks of granulocyte colony-stimulating factor in patients with coronary artery disease SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID ENDOTHELIAL PROGENITOR CELLS; PERIPHERAL-BLOOD STEM; CYTOKINE-INDUCED MOBILIZATION; C-REACTIVE PROTEIN; G-CSF; ANGINA; NEOVASCULARIZATION; TRANSPLANTATION; ISCHEMIA; THERAPY AB OBJECTIVES Cytokine mobilization of progenitor cells from bone marrow may promote myocardial neovascularization with relief of ischemia. BACKGROUND Patients with coronary artery disease (CAD) have low numbers of endothelial progenitor cells compared with healthy subjects. METHODS Granulocyte colony-stimulating factor (G-CSF), 10 mu g/kg/day for five days, was administered to 16 CAD patients. Progenitor cells were measured by flow cytometry; ischemia was assessed by exercise stress testing and by dobutamine stress cardiac magnetic resonance imaging. RESULTS Granulocyte colony-stimulating factor increased CD34+/CD133+ cells in the circulation from 1.5 +/- 0.2 mu l to 52.4 +/- 10.4 mu l (p < 0.001), similar to the response observed in 15 healthy subjects (75.1 +/- 12.6 mu l, p = 0.173). Indices of platelet and coagulation activation were not changed by treatment, but C-reactive protein increased from 4.5 +/- 1.3 mg/l to 8.6 +/- 1.3 mg/l (p = 0.017). Two patients experienced serious adverse events: 1) non-ST-segment elevation myocardial infarction (MI) 8 h after the fifth G-CSF dose, and 2) MI and death 17 days after treatment. At 1 month after treatment, there was no improvement from baseline values (i.e., reduction) in wall motion score (from 25.7 +/- 2.1 to 28.3 +/- 1.9, p = 0.196) or segments with abnormal perfusion (7.6 +/- 1.1 to 7.7 +/- 1.1, p = 0.916) and a trend towards a greater number of ischemic segments (from 4.5 +/- 0.6 to 6.1 +/- 1.0, p = 0.068). There was no improvement in exercise duration at 1 month (p = 0.37) or at 3 months (p = 0.98) versus baseline. CONCLUSIONS Granulocyte colony-stimulating factor administration to CAD patients mobilizes cells with endothelial progenitor potential from bone marrow, but without objective evidence of cardiac benefit and with the potential for adverse outcomes in some patients. C1 NHLBI, Cardiovasc Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Off Biostat Res, NIH, Bethesda, MD 20892 USA. Univ London Kings Coll, Dept Cardiol, London WC2R 2LS, England. Emory Univ, Div Cardiol, Atlanta, GA 30322 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. Univ Chicago Hosp, Chicago, IL 60637 USA. NIH, Dept Transfus Med, Bethesda, MD 20892 USA. NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA. RP Cannon, RO (reprint author), NHLBI, Cardiovasc Branch, NIH, Bldg 10,Room 7B15,10 Ctr Dr,MSC 1650, Bethesda, MD 20892 USA. EM Jonathan.Hill@kcl.ac.uk; cannonr@nih.gov FU NHLBI NIH HHS [Z01 HL005059-04, Z01 HL005064-02] NR 25 TC 143 Z9 149 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 NOV 1 PY 2005 VL 46 IS 9 BP 1643 EP 1648 DI 10.1016/j.jacc.2005.01.067 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 978XH UT WOS:000232905800004 PM 16256862 ER PT J AU Ryder, KM Shorr, RI Bush, AJ Kritchevsky, SB Harris, T Stone, K Cauley, J Tylavsky, FA AF Ryder, KM Shorr, RI Bush, AJ Kritchevsky, SB Harris, T Stone, K Cauley, J Tylavsky, FA TI Magnesium intake from food and supplements is associated with bone mineral density in healthy older white subjects SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE bone mineral density; nutrition; magnesium; osteoporosis; elderly ID POSTMENOPAUSAL WOMEN; PROTEIN-INTAKE; PARATHYROID-HORMONE; VERTEBRAL FRACTURE; RACIAL-DIFFERENCES; DIETARY-INTAKE; ELDERLY-WOMEN; ENERGY-INTAKE; BLACK-WOMEN; LOW-INCOME AB OBJECTIVES: To determine whether magnesium intake from supplemental and dietary sources is associated with bone mineral density (BMD) in older men and women. DESIGN: Cross-sectional. SETTING: Memphis, Tennessee, and Pittsburgh, Pennsylvania. PARTICIPANTS: Two thousand thirty-eight older black and white men and women aged 70 to 79 at baseline enrolled in the Health, Aging and Body Composition Study. MEASUREMENTS: Dietary intake of magnesium was assessed using a semiquantitative food frequency questionnaire, and supplement data were collected based on a medication inventory. BMD of the whole body was obtained using a fan-beam densitometer. Additional covariates included age, body mass index (BMI), smoking status, alcohol use, physical activity, estrogen use, and supplemental calcium (Ca) and vitamin D use. RESULTS: In white, but not black, men and women, magnesium intake was positively associated with BMD of the whole body after adjustment for age, self-report of osteoporosis or fracture in adulthood, caloric intake, Ca and vitamin D intake, BMI, smoking status, alcohol intake, physical activity, thiazide diuretic use, and estrogen use in women (P=.05 for men and P=.005 for women). BMD was 0.04 g/cm(2) higher in white women and 0.02 g/cm(2) higher in white men in the highest than in the lowest quintile of magnesium intake. CONCLUSION: Greater magnesium intake was significantly related to higher BMD in white women and men. The lack of association observed in black women and men may be related to differences in Ca regulation or in nutrient reporting. C1 Univ Tennessee, Dept Med, Div Gen Internal Med, Hlth Sci Ctr, Memphis, TN 38105 USA. Univ Tennessee, Hlth Sci Ctr, Dept Prevent Med, Memphis, TN 38105 USA. Wake Forest Univ, Sch Med, Sticht Ctr Aging, Winston Salem, NC 27109 USA. NIA, Epidemiol Demog & Biometry Program, Bethesda, MD 20892 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. RP Ryder, KM (reprint author), Univ Tennessee, Dept Med, Div Gen Internal Med, Hlth Sci Ctr, 66 N Pauline St,Suite 381, Memphis, TN 38105 USA. EM kryder@utmem.edu RI Cauley, Jane/N-4836-2015; OI Cauley, Jane/0000-0003-0752-4408; Kritchevsky, Stephen/0000-0003-3336-6781 FU NCRR NIH HHS [K23 RR16047]; NIA NIH HHS [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106] NR 45 TC 41 Z9 45 U1 0 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD NOV PY 2005 VL 53 IS 11 BP 1875 EP 1880 DI 10.1111/j.1532-5415.2005.53561.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 977RH UT WOS:000232820400004 PM 16274367 ER PT J AU Terry, DF Pencina, MJ Vasan, RS Murabito, JM Wolf, PA Hayes, MK Levy, D D'Agostino, RB Benjamin, EJ AF Terry, DF Pencina, MJ Vasan, RS Murabito, JM Wolf, PA Hayes, MK Levy, D D'Agostino, RB Benjamin, EJ TI Cardiovascular risk factors predictive for survival and morbidity-free survival in the oldest-old Framingham Heart Study participants SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Editorial Material DE aged; cohort studies; mortality; risk assessment; comorbidity ID ALL-CAUSE MORTALITY; HEALTH-CARE PROFESSIONALS; MIDDLE-AGED MEN; EXCEPTIONAL LONGEVITY; BLOOD-PRESSURE; CIGARETTE-SMOKING; PHYSICAL-ACTIVITY; LIFE EXPECTANCY; LARGE COHORTS; YOUNG-ADULT AB To examine whether midlife cardiovascular risk factors predict survival and survival free of major comorbidities to the age of 85. Prospective community-based cohort study. Framingham Heart Study, Massachusetts. Two thousand five hundred thirty-one individuals (1,422 women) who attended at least two examinations between the ages of 40 and 50. Risk factors were classified at routine examinations performed between the ages of 40 and 50. Stepwise sex-adjusted logistic regression models predicting the outcomes of survival and survival free of morbidity to age 85 were selected from the following risk factors: systolic and diastolic blood pressure, total serum cholesterol, glucose intolerance, cigarette smoking, education, body mass index, physical activity index, pulse pressure, antihypertensive medication, and electrocardiographic left ventricular hypertrophy. More than one-third of the study sample survived to age 85, and 22% of the original study sample survived free of morbidity. Lower midlife blood pressure and total cholesterol levels, absence of glucose intolerance, nonsmoking status, higher educational attainment, and female sex predicted overall and morbidity-free survival. The predicted probability of survival to age 85 fell in the presence of accumulating risk factors: 37% for men with no risk factors to 2% with all five risk factors and 65% for women with no risk factors to 14% with all five risk factors. Lower levels of key cardiovascular risk factors in middle age predicted overall survival and major morbidity-free survival to age 85. Recognizing and modifying these factors may delay, if not prevent, age-related morbidity and mortality. C1 Boston Univ, Med Ctr, Geriatr Sect, Dept Geriatr, Boston, MA 02118 USA. Boston Univ, Med Ctr, Dept Cardiol, Boston, MA 02118 USA. Boston Univ, Med Ctr, Dept Prevent Med, Boston, MA 02118 USA. Boston Univ, Med Ctr, Dept Gen Internal Med, Boston, MA 02118 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Boston Univ, Dept Math & Stat, Boston, MA 02118 USA. NHLBI, Bethesda, MD 20892 USA. RP Terry, DF (reprint author), Boston Univ, Med Ctr, Geriatr Sect, Dept Geriatr, Boston, MA 02118 USA. EM laterry@bu.edu OI Murabito, Joanne/0000-0002-0192-7516; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [N01-HC-25195, K24-HL-04334]; NIA NIH HHS [1 K08 AG022785]; NINDS NIH HHS [5R01-NS-17950] NR 46 TC 65 Z9 68 U1 0 U2 6 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD NOV PY 2005 VL 53 IS 11 BP 1944 EP 1950 DI 10.1111/j.1532-5415.2005.00465.x PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 977RH UT WOS:000232820400013 PM 16274376 ER PT J AU Kim, SW Schou, UK Peters, CD de Seigneux, S Kwon, TH Knepper, MA Jonassen, TEN Frokiaer, J Nielsen, S AF Kim, SW Schou, UK Peters, CD de Seigneux, S Kwon, TH Knepper, MA Jonassen, TEN Frokiaer, J Nielsen, S TI Increased apical targeting of renal epithelial sodium channel subunits and decreased expression of type 2 11 beta-hydroxysteroid dehydrogenase in rats with CCl4-induced decompensated liver cirrhosis SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID NA-CL COTRANSPORTER; APPARENT MINERALOCORTICOID EXCESS; RENIN-ALDOSTERONE SYSTEM; MEDIATED REGULATION; DOWN-REGULATION; HENLES LOOP; KIDNEY; RETENTION; RECEPTOR; ASCITES AB It was hypothesized that dysregulation of renal epithelial sodium channel (ENaC) subunits and/or 11 beta-hydroxysteroid dehydrogenase (11BHSD2) may play a role in the increased sodium retention in liver cirrhosis (LC). Experimental LC was induced in rats by CCL4 (1 ml/kg, intraperitoneally, twice a week) for 12 wk (protocol 1) or for 11 wk (protocol 2). In both protocols, one group of rats with cirrhosis showed significantly decreased urinary sodium excretion and urinary Na/K ratio (group A), whereas a second group exhibited normal urinary sodium excretion (group B) compared with controls, even though extensive ascites was seen in both groups of rats with cirrhosis. In group A, protein abundance of alpha-ENaC was unchanged, whereas beta-ENaC abundance was decreased in the cortex/outer stripe of outer medulla compared with controls. The gamma-ENaC underwent a complex change associated with increased abundance of the 70-kD band with a concomitant decrease in the main 85-kD band, corresponding to an aldosterone effect. In contrast, no changes in the abundance of ENaC subunit were observed in group B. Immunoperoxidase microscopy revealed an increased apical targeting of alpha-, beta-, and gamma-ENaC subunits in distal convoluted tubule (DCT2), connecting tubule (CNT), and cortical and medullary collecting duct segments in group A but not in group B. Immunolabeling intensity of 11BHSD2 in the DCT2, CNT, and cortical collecting duct was significantly reduced in group A but not in group B, and this was confirmed by immunoblotting. In conclusion, increased apical targeting of ENaC subunits combined with diminished abundance of 11BHSD2 in the DCT2, CNT, and cortical collecting duct is likely to play a role in the sodium retaining stage of liver cirrhosis. C1 Aarhus Univ, Water & Salt Res Ctr, DK-8000 Aarhus, Denmark. Chonnam Natl Univ, Sch Med, Dept Internal Med, Gwanju, South Korea. Kyungpook Natl Univ, Sch Med, Dept Biochem & Cell Biol, Taegu, South Korea. NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD USA. Univ Copenhagen, Panum Inst, Dept Pharmacol, Copenhagen, Denmark. RP Nielsen, S (reprint author), Aarhus Univ, Water & Salt Res Ctr, Bldg 233-234, DK-8000 Aarhus, Denmark. EM sn@ana.au.dk OI Frokiaer, Jorgen/0000-0002-6206-8065 FU Intramural NIH HHS [Z01 HL001285-21, Z99 HL999999] NR 47 TC 24 Z9 24 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2005 VL 16 IS 11 BP 3196 EP 3210 DI 10.1681/ASN.2004080721 PG 15 WC Urology & Nephrology SC Urology & Nephrology GA 978BS UT WOS:000232847800010 PM 16192424 ER PT J AU Greene, T Daugirdas, J Depner, T Allon, M Beck, G Chumlea, C Delmez, J Gotch, F Kusek, JW Levin, N Owen, W Schulman, G Star, R Toto, R Eknoyan, G AF Greene, T Daugirdas, J Depner, T Allon, M Beck, G Chumlea, C Delmez, J Gotch, F Kusek, JW Levin, N Owen, W Schulman, G Star, R Toto, R Eknoyan, G CA Hemodialysis Study Grp TI Association of achieved dialysis dose with mortality in the Hemodialysis Study: An example of "dose-targeting bias" SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID MULTICENTER CLINICAL-TRIAL; UREA REDUCTION RATIO; TO-TREAT ANALYSIS; BYPASS-SURGERY; BODY-SIZE; HEMO; SURVIVAL; PREDICTORS; INDEX; OUTCOMES AB In the intention-to-treat analysis of the Hemodialysis Study, all-cause mortality did not differ significantly between the high versus standard hemodialysis dose groups. The association of mortality with delivered dose within each of the two randomized treatment groups was examined, and implications for observational studies were considered. Time-dependent Cox regression was used to relate the relative risk (RR) for mortality to the running mean of the achieved equilibrated Kt/V (eKt/V) over the preceding 4 mo. eKt/V was categorized by quintiles within each dose group. Analyses were controlled for case-mix factors and baseline anthropometric volume. Within each randomized dose group, mortality was elevated markedly when achieved eKt/V was in the lowest quintile (RR, 1.93; 95% confidence interval [CI], 1.40 to 2.66; P < 0.0001 in the standard-dose group; RR, 2.04; 95% CI, 1.50 to 2.76; P < 0.0001 in the high-dose group; RR relative to the middle quintiles). The mortality rate in the lowest eKt/V quintile of the high-dose group was higher than in the full standard-dose group (RR, 1.59; 95% CI, 1.29 to 1.96; P < 0.0001). Each 0.1 eK/V unit below the group median was associated with a 58% higher mortality in the standard-dose group (P < 0.001) and a 37% higher mortality in the high-dose group (P < 0.001). The magnitude of these dose-mortality effects was seven- to 12-fold higher than the upper limit of the 95% CI from the intention-to-treat analysis. The effects were attenuated in lagged analyses but did not disappear. When dialysis dose is targeted closely, as under the controlled conditions of the Hemodialysis Study, patients with the lowest achieved dose relative to their target dose experience markedly increased mortality, to a degree that is not compatible with a biologic effect of dose. The possibility of similar (albeit smaller) biases should be considered when analyzing observational data sets relating mortality to achieved dose of dialysis. C1 Cleveland Clin Fdn, Dept Quantitat Hlth Sci, Cleveland, OH 44195 USA. Univ Illinois, Sch Med, Chicago, IL USA. Univ Calif Davis, Div Nephrol, Sacramento, CA 95817 USA. Univ Alabama, Birmingham, AL USA. Wright State Univ, Boonshoft Sch Med, Dept Community Hlth, Dayton, OH 45435 USA. Washington Univ, Sch Med, Div Renal, St Louis, MO 63110 USA. Univ Calif San Francisco, Sch Med, San Francisco, CA 94143 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. Beth Israel Deaconess Med Ctr, Renal Res Inst, New York, NY 10003 USA. Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA. Vanderbilt Univ, Ctr Med, Nashville, TN 37232 USA. Univ Texas, SW Med Ctr, Dallas, TX 75230 USA. Baylor Coll Med, Houston, TX 77030 USA. RP Greene, T (reprint author), Cleveland Clin Fdn, Dept Biostat & Epidemiol, Wb-4,9500 Euclid Ave, Cleveland, OH 44195 USA. EM tgreene@bio.ri.ccf.org NR 48 TC 57 Z9 58 U1 0 U2 3 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2005 VL 16 IS 11 BP 3371 EP 3380 DI 10.1681/ASN.2005030321 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 978BS UT WOS:000232847800027 PM 16192421 ER PT J AU Menon, V Greene, T Pereira, AA Wang, XL Beck, GJ Kusek, JW Collins, AJ Levey, AS Sarnak, MJ AF Menon, V Greene, T Pereira, AA Wang, XL Beck, GJ Kusek, JW Collins, AJ Levey, AS Sarnak, MJ TI Glycosylated hemoglobin and mortality in patients with nondiabetic chronic kidney disease SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID IMPAIRED GLUCOSE-TOLERANCE; CORONARY-ARTERY-DISEASE; COLORECTAL-CANCER RISK; CARDIOVASCULAR-DISEASE; METABOLIC SYNDROME; DIABETES-MELLITUS; HEART-DISEASE; RANCHO-BERNARDO; US ADULTS; FOLLOW-UP AB in the general population, hyperglycemia in the absence of diabetes may be associated with increased risk for mortality. Hyperglycemia is prevalent in chronic kidney disease; however, the relationship between glycosylated hemoglobin (HbA(1c)) as a marker of chronic hyperglycemia and outcomes has not been studied in nondiabetic chronic kidney disease. HbA(1c) was measured at baseline in the randomized cohort of the Modification of Diet in Renal Disease Study (n = 840). Participants with diabetes (n = 43), fasting glucose levels > 126 mg/dl (n = 20), or missing HbA(1c) levels (n = 9) were excluded. Survival status until December 2000 was obtained from the National Death Index. Death was classified as cardiovascular (CVD) when the primary cause was International Classification of Disease, Ninth Revision codes 390 to 459. Cox models were performed to assess the relationship of HbA(1c) with all-cause and CVD mortality. Mean (SD) age was 52 (12) years, and mean (SD) GFR was 32 (12) ml/min per 1.73 m(2). Eighty-six percent of participants were white, and 61% were male. Mean (SD) HbA(1c) was 5.6% (0.5). A total of 169 (22%) patients died, 96 (13%) from CVD. After adjustment for randomization assignments and demographic, CVD, and kidney disease factors, HbA(1c) was a predictor of all-cause mortality (hazard ratio per 1% increase 1.73; 95% confidence interval 1.24 to 2.41; P = 0.001). There was a trend toward statistical significance in the relationship between HbA(1c), and CVD mortality (hazard ratio per 1% increase 1.53; 95% confidence interval 0.96 to 2.43; P = 0.07). HbA(1c), is associated with increased mortality in nondiabetic kidney disease. Hyperglycemia may be a potential therapeutic target and HbA(1c) may be important as a risk stratification tool in this high-risk population. C1 Tufts Univ, New England Med Ctr, Dept Med, Div Nephrol, Boston, MA 02111 USA. Cleveland Clin Fdn, Dept Biostat & Epidemiol, Cleveland, OH 44195 USA. NIH, Bethesda, MD 20892 USA. Hennepin Cty Med Ctr, Div Nephrol, Minneapolis, MN 55415 USA. RP Sarnak, MJ (reprint author), Tufts Univ, 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 [K23 DK02904, K23 DK67303, UO1 DK35073] NR 40 TC 37 Z9 39 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2005 VL 16 IS 11 BP 3411 EP 3417 DI 10.1681/ASN.2005050552 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 978BS UT WOS:000232847800032 PM 16207824 ER PT J AU Martinez, AW Recht, NS Hostetter, TH Meyer, TW AF Martinez, AW Recht, NS Hostetter, TH Meyer, TW TI Removal of p-cresol sulfate by hemodialysis SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID PROTEIN-BOUND SOLUTES; CHRONIC-RENAL-FAILURE; UREMIC SOLUTES; VOLATILE PHENOLS; INDOXYL SULFATE; ORAL SORBENT; SERUM; MEMBRANE; TOXINS; CLEARANCE AB Protein-bound solutes are poorly cleared by dialysis. Among the most extensively studied of these solutes is p-cresol, which has been shown to be toxic in vitro. This study examined the form in which p-cresol circulates and quantified its removal by hemodialysis. HPLC analysis of plasma from hemodialysis patients contained a peak whose mobility corresponded to synthetic p-cresol sulfate (PCS) but no detectable unconjugated p-cresol. Treatment with sulfatase resulted in recovery of this peak as p-cresol, confirming its identity. Subsequent studies compared the removal of PCS and another protein-bound solute, indican, to the removal of urea during clinical hemodialysis treatments. PCS and indican were 94 +/- 1% and 93 +/- 2% bound to plasma protein, respectively. Protein-binding caused a predictable decrease in measured dialytic clearance, which averaged 20 +/- 4 ml/min for PCS and 25 +/- 5 ml/min for indican as compared with 260 +/- 20 ml/min for urea. Volumes of distribution for the protein-bound solutes were greater than the plasma volume, averaging 15 +/- 7 L for PCS and 14 +/- 3 L for indican as compared with 37 +/- 7 for urea. Solute reduction ratios were 20 +/- 9% for PCS, 30 +/- 7% for indican, and 69 +/- 5% for urea. We conclude that p-cresol circulates in the form of its sulfate conjugate, PCS. PCS is poorly removed by hemodialysis because its clearance is limited by protein binding and the ratio of its volume of distribution to its clearance is high. C1 Vet Assoc, Dept Med, Palo Alto, CA USA. Stanford Univ, Dept Med, Palo Alto, CA 94304 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. RP Meyer, TW (reprint author), Palo Alto VAHCS, Nephrol 111R,3801 Miranda Ave, Palo Alto, CA 94303 USA. EM twmeyer@stanford.edu FU NIDDK NIH HHS [R01 DK52841] NR 40 TC 132 Z9 140 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2005 VL 16 IS 11 BP 3430 EP 3436 DI 10.1681/ASN.2005030310 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 978BS UT WOS:000232847800034 PM 16120820 ER PT J AU Mendy, M Kirk, GD van der Sande, M Jeng-Barry, A Lesi, OA Hainaut, P Sam, O McConkey, S Whittle, H AF Mendy, M Kirk, GD van der Sande, M Jeng-Barry, A Lesi, OA Hainaut, P Sam, O McConkey, S Whittle, H TI Hepatitis B surface antigenaemia and alpha-foetoprotein detection from dried blood spots: applications to field-based studies and to clinical care in hepatitis B virus endemic areas SO JOURNAL OF VIRAL HEPATITIS LA English DT Article DE alpha-foetoprotein; chronic hepatitis B virus infection; dried blood spot; hepatitis B surface antigen; hepatocellular carcinoma ID CHRONIC LIVER-DISEASE; 2 GAMBIAN VILLAGES; HEPATOCELLULAR-CARCINOMA; WEST-AFRICA; PLASMA DNA; SERUM; DIAGNOSIS; INFECTION; MARKER; CANCER AB In many resource-limited regions with endemic hepatitis B virus (HBV), there is limited infrastructure to collect, process, transport, and store blood samples for identification of persons with chronic HBV infection or with hepatocellular carcinoma (HCC). We describe the application of a simple technique using commercially available kits for detection of HBV surface antigen (HBsAg) and alpha-foetoprotein (AFP) in dried blood spots (DBS) collected on filter paper. Study participants included subjects with and without chronic HBV infection and subjects with HCC or cirrhosis. Three to five blood drops were dried on filter paper. Dried blood (equivalent to 20 mu L) was eluted and tested for HBsAg by Determine(TM) HBsAg and for AFP by counter-current immuno-electrophoresis and radio-immunoassay (RIA). The primary analysis focused on comparison of DBS results to serum testing results as the gold standard. The sensitivity of DBS for detecting chronic HBV infection was 96% (98-98) with specificity of 100% (CI 99-100). Sensitivity of DBS in detecting AFP compared with serum RIA was 73% (60-86) with specificity of 90% (81-98). Both HBsAg and AFP recovery were unaffected when DBS were left at room temperature (30-33 degrees C) and under humid conditions for up to 28 days prior to elution. We conclude that DBS can be reliably used as an economical and logical alternative for detection of HBsAg in chronically infected patients and for AFP-based diagnosis of HCC in clinical situations which preclude adequate collection and processing of blood samples. Both research-oriented field studies and routine clinical care may benefit from application of these techniques in resource-limited settings. C1 MRC Fajara, Banjul, Gambia. MRC, IARC, Gambia Hepatitis Intervent Study, Banjul, Gambia. Int Agcy Res Canc, F-69372 Lyon, France. Govt Gambia, Dept Hlth & Social Welf, Banjul, Gambia. NCI, Viral Epidemiol Branch, NIH, DHHS, Bethesda, MD 20892 USA. RP Mendy, M (reprint author), MRC Fajara, POB 273, Banjul, Gambia. EM mmendy@mrc.gm RI Kirk, Gregory/A-8484-2009; McConkey, Samuel/E-7307-2012; OI McConkey, Samuel/0000-0001-9085-7793 NR 32 TC 19 Z9 20 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1352-0504 J9 J VIRAL HEPATITIS JI J. Viral Hepatitis PD NOV PY 2005 VL 12 IS 6 BP 642 EP 647 DI 10.1111/j.1365-2893.2005.00641.x PG 6 WC Gastroenterology & Hepatology; Infectious Diseases; Virology SC Gastroenterology & Hepatology; Infectious Diseases; Virology GA 975JX UT WOS:000232659300011 PM 16255766 ER PT J AU Bukreyev, A Huang, ZH Yang, LJ Elankumaran, S St Claire, M Murphy, BR Samal, SK Collins, PL AF Bukreyev, A Huang, ZH Yang, LJ Elankumaran, S St Claire, M Murphy, BR Samal, SK Collins, PL TI Recombinant newcastle disease virus expressing a foreign viral antigen is attenuated and highly immunogenic in primates SO JOURNAL OF VIROLOGY LA English DT Article ID RESPIRATORY SYNCYTIAL VIRUS; HEMAGGLUTININ-NEURAMINIDASE PROTEIN; AFRICAN-GREEN MONKEYS; MUCOSAL IMMUNIZATION; INFECTIOUS-DISEASES; RHESUS-MONKEYS; RNA-SYNTHESIS; SENDAI VIRUS; F-PROTEIN; TYPE-3 AB Paramyxoviruses such as human parainfluenza viruses that bear inserts encoding protective antigens of heterologous viruses can induce an effective immunity against the heterologous viruses in experimental animals. However, vectors based on common human pathogens would be expected to be restricted in replication in the adult human population due to high seroprevalence, an effect that would reduce vector immunogenicity. To address this issue, we evaluated Newcastle disease virus (NDV), an avian paramyxovirus that is serotypically distinct from common human pathogens, as a vaccine vector. Two strains were evaluated: the attenuated vaccine strain LaSota (NDV-LS) that replicates mostly in the chicken respiratory tract and the Beaudette C (NDV-BC) strain of intermediate virulence that produces mild systemic infection in chickens. A recombinant version of each virus was modified by the insertion, between the P and M genes, of a gene cassette encoding the human parainfluenza virus type 3 (HPIV3) hemagglutinin-neuraminidase (HN) protein, a test antigen with considerable historic data. The recombinant viruses were administered to African green monkeys (NDV-BC and NDV-LS) and rhesus monkeys (NDV-BC only) by combined intranasal and intratracheal routes at a dose of 10(6.5) PFU per site, with a second equivalent dose administered 28 days later. Little or no virus shedding was detected in nose-throat swabs or tracheal lavages following immunization with either strain. In a separate experiment, direct examination of lung tissue confirmed a highly attenuated, restricted pattern of replication by parental NDV-BC. The serum antibody response to the foreign HN protein induced by the first immunization with either NDV vector was somewhat less than that observed following a wild-type HPIV3 infection; however, the titer following the second dose exceeded that observed with HPIV3 infection, even though HPIV3 replicates much more efficiently than NDV in these animals. NDV appears to be a promising vector for the development of vaccines for humans; one application would be in controlling localized outbreaks of emerging pathogens. C1 NIAID, LID, NIH, Bethesda, MD 20892 USA. Univ Maryland, Virginia Maryland Reg Coll Vet Med, College Pk, MD 20742 USA. Bioqual, Rockville, MD 20850 USA. RP Bukreyev, A (reprint author), NIAID, LID, NIH, 50 South Dr,Rm 6505, Bethesda, MD 20892 USA. EM abukreyev@niaid.nih.gov RI Subbiah, Elankumaran/E-9277-2010 OI Subbiah, Elankumaran/0000-0003-4135-9477 FU Intramural NIH HHS NR 42 TC 67 Z9 75 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 2005 VL 79 IS 21 BP 13275 EP 13284 DI 10.1128/JVI.79.21.13275-13284.2005 PG 10 WC Virology SC Virology GA 975MJ UT WOS:000232666300008 PM 16227250 ER PT J AU Shin, EC Protzer, U Untergasser, A Feinstone, SM Rice, CM Hasselschwert, D Rehermann, B AF Shin, EC Protzer, U Untergasser, A Feinstone, SM Rice, CM Hasselschwert, D Rehermann, B TI Liver-directed gamma interferon gene delivery in chronic hepatitis C SO JOURNAL OF VIROLOGY LA English DT Article ID VIRUS-INFECTION; IMMUNE-RESPONSES; VIRAL CLEARANCE; PLUS RIBAVIRIN; T-CELLS; EXPRESSION; REPLICATION; PERSISTENCE; LYMPHOCYTES; CHIMPANZEES AB Gamma interferon (IFN-gamma) has been shown to inhibit replication of subgenomic and genomic hepatitis C virus (HCV) RNAs in vitro and to noncytolytically suppress hepatitis B virus (HBV) replication in vivo. IFN-gamma is also known for its immunomodulatory effects and as a marker of a successful cellular immune response to HCV. Therapeutic expression of IFN-gamma in the liver may therefore facilitate resolution of chronic hepatitis C, an infection that is rarely resolved spontaneously. To analyze immunomodullatory and antiviral effects of liver-specific IFN-gamma expression in vivo, we intravenously injected two persistently HCV-infected chimpanzees twice with a recombinant, replication-deficient HBV vector and subsequently with a recombinant adenoviral vector. These vectors expressed human IFN-gamma under control of HBV- and liver-specific promoters, respectively. Gene transfer resulted in a transient increase of intrahepatic IFN-gamma mRNA, without increase in serum alanine aminotransferase levels. Ex vivo analysis of peripheral blood lymphocytes demonstrated enhanced CD16 expression on T cells and upregulation of the liver-homing marker CXCR3. Moreover, an increased frequency of HCV-specific T cells was detected ex vivo in the peripheral blood and in vitro in liver biopsy-derived, antigen-nonspecifically expanded T-cell lines. None of these immunologic effects were observed in the third chimpanzee injected with an HBV control vector. Despite these immunologic effects of the experimental vector, however, IFN-gamma gene transfer did not result in a significant and long-lasting decrease of HCV titers. In conclusion, liver-directed IFN-gamma gene delivery resulted in HCV-specific and nonspecific activation of cellular immune responses but did not result in effective control of HCV replication. C1 NIDDK, Liver Dis Branch, NIH, DHHS, Bethesda, MD 20892 USA. Univ Cologne, Mol Infektiol Zentrum Mol Med, IMMIH, Cologne, Germany. US FDA, Ctr Biol Evaluat & Res, Lab Hepatatis Viruses, Bethesda, MD 20014 USA. Rockefeller Univ, Ctr Study Hepatitis C, New York, NY 10021 USA. Univ Louisville, New Iberia Res Ctr, New Iberia, LA USA. RP Rehermann, B (reprint author), NIDDK, Liver Dis Branch, NIH, DHHS, 10 Ctr Dr,Room 9B16, Bethesda, MD 20892 USA. EM Rehermann@nih.gov RI Shin, Eui-Cheol/C-1690-2011 FU NCI NIH HHS [CA85883-01, R01 CA085883] NR 42 TC 17 Z9 20 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 2005 VL 79 IS 21 BP 13412 EP 13420 DI 10.1128/JVI.79.21.13412-13420.2005 PG 9 WC Virology SC Virology GA 975MJ UT WOS:000232666300020 PM 16227262 ER PT J AU Lustig, S Fogg, C Whitbeck, JC Eisenberg, RJ Cohen, GH Moss, B AF Lustig, S Fogg, C Whitbeck, JC Eisenberg, RJ Cohen, GH Moss, B TI Combinations of polyclonal or monoclonal antibodies to proteins of the outer membranes of the two infectious forms of vaccinia virus protect mice against a lethal respiratory challenge SO JOURNAL OF VIROLOGY LA English DT Article ID GREEN FLUORESCENT PROTEIN; DISULFIDE BOND FORMATION; HERPES-SIMPLEX-VIRUS; SMALLPOX VACCINE; IN-VIVO; NEUTRALIZATION; GLYCOPROTEIN; IMMUNITY; ENTRY; LOCALIZATION AB Previous studies demonstrated that antibodies to live vaccinia virus infection are needed for optimal protection against orthopoxvirus infection. The present report is the first to compare the protective abilities of individual and combinations of specific polyclonal and monoclonal antibodies that target proteins of the intracellular (IMV) and extracellular (EV) forms of vaccinia virus. The antibodies were directed to one IMV membrane protein, L1, and to two outer EV membrane proteins, A33 and B5. In vitro studies showed that the antibodies to L1 neutralized IMV and that the antibodies to A33 and B5 prevented the spread of EV in liquid medium. Prophylactic administration of individual antibodies to BALB/c mice partially protected them against disease following intranasal challenge with lethal doses of vaccinia virus. Combinations of antibodies, particularly anti-L1 and -A33 or -L1 and -B5, provided enhanced protection when administered I day before or 2 days after challenge. Furthermore, the protection was superior to that achieved with pooled immune gamma globulin from human volunteers inoculated with live vaccinia virus. In addition, single injections of anti-L1 plus anti-A33 antibodies greatly delayed the deaths of severe combined immunodeficiency mice challenged with vaccinia virus. These studies suggest that antibodies to two or three viral membrane proteins optimally derived from the outer membranes of IMV and EV, may be beneficial for prophylaxis or therapy of orthopoxvirus infections. C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. Univ Penn, Sch Dent, Philadelphia, PA 19104 USA. Univ Penn, Sch Vet Med, Philadelphia, PA 19104 USA. RP Moss, B (reprint author), NIAID, Viral Dis Lab, NIH, 4 Mem Dr,MSC 0445, Bethesda, MD 20892 USA. EM bmoss@nih.gov FU NIAID NIH HHS [AI53044, U54 AI057168] NR 51 TC 86 Z9 87 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 2005 VL 79 IS 21 BP 13454 EP 13462 DI 10.1128/JVI.79.21.13454-13462.2005 PG 9 WC Virology SC Virology GA 975MJ UT WOS:000232666300024 PM 16227266 ER PT J AU Chang, KW Julias, JG Alvord, WG Oh, J Hughes, SH AF Chang, KW Julias, JG Alvord, WG Oh, J Hughes, SH TI Alternate polypurine tracts (PPTs) affect the Rous sarcoma virus RNase H cleavage specificity and reveal a preferential cleavage following a GA dinucleotide sequence at the PPT-U3 junction SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; PLUS-STRAND DNA; HIV-1 REVERSE-TRANSCRIPTASE; IN-VIVO; RETROVIRAL VECTORS; CELL-LINE; TYPE-1; REPLICATION; MUTATIONS; DOMAIN AB Retroviral polypurine tracts (PPTs) serve as primers for plus-strand DNA synthesis during reverse transcription. The generation and removal of the PPT primer requires specific cleavages by the RNase H activity of reverse transcriptases; removal of the PPT primer defines the left end of the linear viral DNA. We replaced the endogenous PPT from RSVP(A)Z, a replication-competent shuttle vector based on Rous sarcoma virus (RSV), with alternate retroviral PPTs and the duck hepatitis B virus "PPT." Viruses in which the endogenous RSV PPT was replaced with alternate PPTs had lower relative titers than the wild-type virus. 2-LTR circle junction analysis showed that the alternate PPTs caused significant decreases in the fraction of viral DNAs with complete (consensus) ends and significant increases in the insertion of part or all of the PPT at the 2-LTR circle junctions. The last two nucleotides in the 3' end of the RSV PPT are GA. Examination of the (mis)cleavages of the alternate PPTs revealed preferential cleavages after GA dinucleotide sequences. Replacement of the terminal 3' A of the RSV PPT with G caused a preferential miscleavage at a GA sequence spanning the PPT-U3 boundary, resulting in the deletion of the terminal adenine normally present at the 5' end of the U3. A reciprocal G-to-A substitution at the 3' end of the murine leukemia virus PPT increased the relative titer of the chimeric RSV-based virus and the fraction of consensus 2-LTR circle junctions. C1 NCI, HIV Drug Resistance Program, Ft Detrick, MD 21702 USA. SAIC Frederick, Basic Res Program, Frederick, MD USA. NCI, Data Management Serv, Ft Detrick, MD 21702 USA. RP Hughes, SH (reprint author), NCI, HIV Drug Resistance Program, POB B,Bldg 539,Rm 130A, Ft Detrick, MD 21702 USA. EM hughes@ncifcrf.gov FU Intramural NIH HHS; NCI NIH HHS [N01CO12400, N01-CO-12400] NR 31 TC 4 Z9 4 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 2005 VL 79 IS 21 BP 13694 EP 13704 DI 10.1128/JVI.79.21.13694-13704.2005 PG 11 WC Virology SC Virology GA 975MJ UT WOS:000232666300047 PM 16227289 ER PT J AU Yedavalli, VSRK Shih, HM Chiang, YP Lu, CY Chang, LY Chen, MY Chuang, CY Dayton, AI Jeang, KT Huang, LM AF Yedavalli, VSRK Shih, HM Chiang, YP Lu, CY Chang, LY Chen, MY Chuang, CY Dayton, AI Jeang, KT Huang, LM TI Human immunodeficiency virus type 1 Vpr interacts with antiapoptotic mitochondrial protein HAX-1 SO JOURNAL OF VIROLOGY LA English DT Article ID ADENINE-NUCLEOTIDE TRANSLOCATOR; APOPTOSIS-INDUCING FACTOR; PROGRAMMED CELL-DEATH; HIV-1 VPR; T-CELLS; MEMBRANE PERMEABILIZATION; NUCLEAR-LOCALIZATION; VIRAL EXPRESSION; EBNA-LP; CYCLE AB Human immunodeficiency virus type 1 viral protein R (Vpr) is required for viral pathogenesis and has been implicated in T-cell apoptosis through its activation of caspase 3 and caspase 9 and perturbation of mitochondrial membrane potential. To understand better Vpr-mitochondria interaction, we report here the identification of antiapoptotic mitochondrial protein HAX-1 as a novel Vpr target. We show that Vpr and HAX-1 physically associate with each other. Overexpression of Vpr in cells dislocates HAX-1 from its normal residence in mitochondria and creates mitochondrion instability and cell death. Conversely, overexpression of HAX-1 suppressed the proapoptotic activity of Vpr. C1 NIAID, Mol Virol Sect, Mol Microbiol Lab, Bethesda, MD 20892 USA. Natl Taiwan Univ Hosp, Acad Sinica, Inst Biomed Sci, Taipei, Taiwan. Natl Taiwan Univ Hosp, Dept Pediat, Taipei, Taiwan. Natl Taiwan Univ Hosp, Dept Internal Med, Taipei, Taiwan. Food & Drug Adm, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Jeang, KT (reprint author), NIH, Bldg 4,Room 306,9000 Rockville Pike, Bethesda, MD 20892 USA. EM kj7e@nih.gov; lmhuang@ha.mc.ntu RI Jeang, Kuan-Teh/A-2424-2008; OI Chang, Luan-Yin/0000-0003-2632-1956; LU, CHUN-YI/0000-0002-5240-2808; Huang, Li-Min/0000-0002-9291-260X NR 61 TC 57 Z9 61 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 2005 VL 79 IS 21 BP 13735 EP 13746 DI 10.1128/JVI.79.21.13735-13746.2005 PG 12 WC Virology SC Virology GA 975MJ UT WOS:000232666300051 PM 16227293 ER PT J AU Dey, AK Khati, M Tang, M Wyatt, R Lea, SM James, W AF Dey, AK Khati, M Tang, M Wyatt, R Lea, SM James, W TI An aptamer that neutralizes R5 strains of human immunodeficiency virus type 1 blocks gp120-CCR5 interaction SO JOURNAL OF VIROLOGY LA English DT Article ID ENVELOPE GLYCOPROTEIN GP120; HIV-1 ENTRY; RECEPTOR-BINDING; STRUCTURAL-CHARACTERIZATION; ANTIBODY 2G12; CELL-FUSION; N-TERMINUS; CCR5; CD4; CARBOHYDRATE AB We recently described the isolation and structural characterization of 2'-fluoropyrimidine-substituted RNA aptamers that bind to gp120 of R5 strains of human immunodeficiency virus type 1 and thereby potently neutralize the infectivity of phylogenetically diverse R5 strains. Here we investigate the physical basis of their antiviral action. We show that both N-linked oligosaccharides and the variable loops V1/V2 and V3 are not required for binding of one aptamer, B40, to gp120. Using surface plasmon resonance binding analyses, we show that the aptamer binds to the CCR5-binding site on gp120 in a relatively CD4-independent manner, providing a mechanistic explanation for its neutralizing potency. C1 Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England. Univ Oxford, Lab Mol Biophys, Dept Biochem, Oxford OX1 3RE, England. NIAID, Vaccines Res Ctr, NIH, Bethesda, MD 20892 USA. RP James, W (reprint author), Univ Oxford, Sir William Dunn Sch Pathol, S Pk Rd, Oxford OX1 3RE, England. EM william.james@pathology.oxford.ac.uk RI Lea, Susan/B-7678-2009; Dey, Antu/A-1305-2013; OI Lea, Susan/0000-0001-9287-8053; james, william/0000-0002-2506-1198 FU Wellcome Trust NR 39 TC 53 Z9 56 U1 0 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 2005 VL 79 IS 21 BP 13806 EP 13810 DI 10.1128/JVI.79.21.13806-13810.2005 PG 5 WC Virology SC Virology GA 975MJ UT WOS:000232666300059 PM 16227301 ER PT J AU Ott, DE Coren, LV Gagliardi, TD AF Ott, DE Coren, LV Gagliardi, TD TI Redundant roles for nucleocapsid and matrix RNA-binding sequences in human immunodeficiency virus type 1 assembly SO JOURNAL OF VIROLOGY LA English DT Article ID MURINE LEUKEMIA-VIRUS; ROUS-SARCOMA-VIRUS; IN-VITRO; GAG POLYPROTEIN; BASIC RESIDUES; GENOMIC RNA; PARTICLE-PRODUCTION; CELLULAR-PROTEINS; TERMINAL DOMAIN; VIRAL-RNA AB RNA appears to be required for the assembly of retroviruses. This is likely due to binding of RNA by multiple Gags, which in turn organizes and stabilizes the Gag-Gag interactions that form the virion. While the nucleocapsid (NC) domain is the most conspicuous RNA-binding region of the human immunodeficiency virus type I (HIV-1) Gag polyprotein, we have previously shown that NC is not strictly required for efficient particle production. To determine if an RNA requirement for HIV-1 assembly exists, we analyzed virions produced by an NC deletion mutant for the presence of RNA. The results revealed that virions without NC still contained significant amounts of RNA. Since these packaged RNAs are probably incorporated by other RNA-binding sequences in Gag, an RNA-binding site in the matrix protein (MA) of Gag was mutated. While this mutation did not interfere with HIV-1 replication, a construct with both MA and NC mutations (MX/NX) failed to produce particles. The MX/NX mutant was rescued in trans by coassembly with several forms of Gag: wild-type Gag, either of the single-mutant Gags, or Gag truncations that contain MA or NC sequences. Addition of basic sequences to the MX/NX mutant partially restored particle production, consistent with a requirement for Gag-RNA binding in addition to Gag-Gag interactions. Together, these results support an RNA-binding requirement for Gag assembly, which relies on binding of RNA by MA or NC sequences to condense, organize, and stabilize the HIV-1 Gag-Gag interactions that form the virion. C1 SAIC Frederick Inc, Basic Res Program, NCI, Frederick, MD 21702 USA. RP Ott, DE (reprint author), SAIC Frederick Inc, Basic Res Program, NCI, Frederick, MD 21702 USA. EM ott@ncifcrf.gov FU NCI NIH HHS [N01-CO-12400, N01CO12400] NR 63 TC 61 Z9 62 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD NOV PY 2005 VL 79 IS 22 BP 13839 EP 13847 DI 10.1128/JVI.79.22.13839-13847.2005 PG 9 WC Virology SC Virology GA 980ER UT WOS:000232997500001 PM 16254319 ER PT J AU Kong, WP Xu, L Stadler, K Ulmer, JB Abrignani, S Rappuoli, R Nabel, GJ AF Kong, WP Xu, L Stadler, K Ulmer, JB Abrignani, S Rappuoli, R Nabel, GJ TI Modulation of the immune response to the severe acute respiratory syndrome spike glycoprotein by gene-based and inactivated virus immunization SO JOURNAL OF VIROLOGY LA English DT Article ID ADENOVIRAL VACCINE VECTOR; TYPE-1 DNA VACCINES; PRIME-PROTEIN BOOST; CD8(+) T-CELLS; SARS-CORONAVIRUS; CPG OLIGODEOXYNUCLEOTIDES; PROTECTIVE IMMUNITY; BALB/C MICE; INTRANASAL IMMUNIZATION; NONHUMAN-PRIMATES AB Although the initial isolates of the severe acute respiratory syndrome (SARS) coronavirus (CoV) are sensitive to neutralization by antibodies through their spike (S) glycoprotein, variants of S have since been identified that are resistant to such inhibition. Optimal vaccine strategies would therefore make use of additional determinants of immune recognition, either through cellular or expanded, cross-reactive humoral immunity. Here, the cellular and humoral immune responses elicited by different combinations of gene-based and inactivated viral particles with various adjuvants have been assessed. The T-cell response was altered by different prime-boost immunizations, with the optimal CD8 immunity induced by DNA priming and replication-defective adenoviral vector boosting. The humoral immune response was enhanced most effectively through the use of inactivated virus with adjuvants, either MF59 or alum, and was associated with stimulation of the CD4 but not the CD8 response. The use of inactivated SARS virus with MF59 enhanced the CD4 and antibody response even after gene-based vaccination. Because both cellular and humoral immune responses are generated by gene-based vaccination and inactivated viral boosting, this strategy may prove useful in the generation of SARS-CoV vaccines. C1 NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. Chiron Corp, Vaccines Res, I-53100 Siena, Italy. RP Nabel, GJ (reprint author), NIAID, Vaccine Res Ctr, NIH, Bldg 40,Room 4502,MSC-3005,40 Convent Dr, Bethesda, MD 20892 USA. EM gnabel@nih.gov OI Abrignani, Sergio/0000-0002-0794-3285 FU Intramural NIH HHS; NIAID NIH HHS [Z01 AI005056-03] NR 78 TC 23 Z9 23 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 2005 VL 79 IS 22 BP 13915 EP 13923 DI 10.1128/JVI.79.22.13915-13923.2005 PG 9 WC Virology SC Virology GA 980ER UT WOS:000232997500009 PM 16254327 ER PT J AU Cai, ZH Zhang, C Chang, KS Jiang, JY Ahn, BC Wakita, T Liang, TJ Luo, GX AF Cai, ZH Zhang, C Chang, KS Jiang, JY Ahn, BC Wakita, T Liang, TJ Luo, GX TI Robust production of infectious hepatitis C virus (HCV) from stably HCV cDNA-transfected human hepatoma cells SO JOURNAL OF VIROLOGY LA English DT Article ID RNA REPLICATION; IN-VITRO; EFFICIENT REPLICATION; SUBGENOMIC REPLICON; SEQUENCE-ANALYSIS; VIRAL-INFECTION; 3 TERMINUS; GENOME; CULTURE; REGION AB Hepatitis C virus (HCV) chronically infects approximately 170 million people worldwide, with an increased risk of developing cirrhosis and hepatocellular carcinoma. The study of HCV replication and pathogenesis has been hampered by the lack of an efficient stable cell culture system and small-animal models of HCV infection and propagation. In an effort to develop a robust HCV infection system, we constructed stable human hepatoma cell lines that contain a chromosomally integrated genotype 2a HCV cDNA and constitutively produce infectious virus. Transcriptional expression of the full-length HCV RNA genome is under the control of a cellular Pol II polymerase promoter at the 5' end and a hepatitis delta virus ribozyme at the 3' end. The resulting HCV RNA was expressed and replicated efficiently, as shown by the presence of high levels of HCV proteins as well as both positive- and negative-strand RNAs in the stable Huh7 cell lines. Stable cell lines robustly produce HCV virions with up to 108 Copies of HCV viral RNA per milliliter (ml) of the culture medium. Subsequent infection of naive Huh7.5 cells with HCV released from the stable cell lines resulted in high levels of HCV proteins and RNAs. Additionally, HCV infection was inhibited by monoclonal antibodies specific to CD81 and the HCV envelope glycoproteins El and E2, and HCV replication was suppressed by alpha interferon. Collectively, these results demonstrate the establishment of a stable HCV culture system that robustly produces infectious virus, which will allow the study of each aspect of the entire HCV life cycle. C1 Univ Kentucky, Coll Med, Dept Microbiol Immunol & Mol Genet, Lexington, KY 40536 USA. Tokyo Metropolitan Inst Neurosci, Dept Microbiol & Immunol, Tokyo 1838526, Japan. NIDDKD, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. RP Luo, GX (reprint author), Univ Kentucky, Coll Med, Dept Microbiol Immunol & Mol Genet, 800 Rose St, Lexington, KY 40536 USA. EM gluo0@uky.edu FU Intramural NIH HHS; NCI NIH HHS [CA093712, R01 CA093712]; NIAID NIH HHS [AI51592, R01 AI051592] NR 44 TC 113 Z9 124 U1 2 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 2005 VL 79 IS 22 BP 13963 EP 13973 DI 10.1128/JVI.79.22.13963-13973.2005 PG 11 WC Virology SC Virology GA 980ER UT WOS:000232997500014 PM 16254332 ER PT J AU Beer, BE Brown, CR Whitted, S Goldstein, S Goeken, R Plishka, R Buckler-White, A Hirsch, VM AF Beer, BE Brown, CR Whitted, S Goldstein, S Goeken, R Plishka, R Buckler-White, A Hirsch, VM TI Immunodeficiency in the absence of high viral load in pig-tailed macaques infected with simian immunodeficiency virus SIVsun or SIVlhoest SO JOURNAL OF VIROLOGY LA English DT Article ID AFRICAN-GREEN MONKEY; CD4(+) T-CELLS; NATURAL INFECTION; IN-VIVO; MANDRILLUS-SPHINX; SOOTY MANGABEYS; DISEASE PROGRESSION; IMMUNE-DEFICIENCY; SIVAGM INFECTION; TANTALUS MONKEYS AB Simian immunodeficiency virus (SIV) is known to result in an asymptomatic infection of its natural African monkey host. However, some SIV strains are capable of inducing AIDS-like symptoms and death upon experimental infection of Asian macaques. To further investigate the virulence of natural SIV isolates from African monkeys, pig-tailed (PT) macaques were inoculated intravenously with either of two recently discovered novel lentiviruses, SIVIhoest and SIVsun. Both viruses were apparently apathogenic in their natural hosts but caused immunodeficiency in PT macaques. Infection was characterized by a progressive loss of CD4(+) lymphocytes in the peripheral blood and lymph nodes, generalized lymphoid depletion, a wasting syndrome, and opportunistic infections, such as Mycobacterium avium or Pneumocystis carinii infections. However, unlike SIVsm/mac infection of macaques, SIVIhoest and SIVsun infections in PT macaques were not accompanied by high viral loads during the chronic disease stage. In addition, no significant correlation between the viral load at set point (12 weeks postinfection) and survival could be found. Five out of eight SIVIhoest-infected and three out of four SIVsun-infected macaques succumbed to AIDS during the first 5 years of infection. Thus, the survival of SIVsun- and SMhoest-infected animals was significantly longer than that of SIVagm- or SIVsm-infected macaques. All PT macaques maintained strong SIV antibody responses despite progression to SIV-induced AIDS. The development of immunodeficiency in the face of low viremia suggests that SIVIhoest and SIVsun infections of macaques may model unique aspects of the pathogenesis of human immunodeficiency virus infection in humans. C1 NIAID, Mol Microbiol Lab, NIH, Rockville, MD 20852 USA. RP Hirsch, VM (reprint author), NIAID, Mol Microbiol Lab, NIH, Bldg 4,Room B1-41,4 Ctr Dr, Rockville, MD 20852 USA. EM vhirsch@niaid.nih.gov NR 69 TC 24 Z9 25 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 2005 VL 79 IS 22 BP 14044 EP 14056 DI 10.1128/JVI.79.22.14044-14056.2005 PG 13 WC Virology SC Virology GA 980ER UT WOS:000232997500021 PM 16254339 ER PT J AU Wang, KN Lau, TY Morales, M Mont, EK Straus, SE AF Wang, KN Lau, TY Morales, M Mont, EK Straus, SE TI Laser-capture microdissection: Refining estimates of the quantity and distribution of latent herpes simplex virus 1 and varicella-zoster virus DNA in human trigeminal ganglia at the single-cell level SO JOURNAL OF VIROLOGY LA English DT Article ID HERPES-SIMPLEX-VIRUS; GENOME COPY NUMBER; TYPE-1 LATENCY; IN-VIVO; SPONTANEOUS REACTIVATION; GENE-EXPRESSION; INFECTED NEURONS; TRANSCRIPT EXPRESSION; INSITU HYBRIDIZATION; MOLECULAR ANALYSIS AB There remains uncertainty and some controversy about the percentages and types of cells in human sensory nerve ganglia that harbor latent herpes simplex virus 1 (HSV-1) and varicella-zoster virus (VZV) DNA. We developed and validated laser-capture microdissection and real-time PCR (LCM/PCR) assays for the presence and copy numbers of HSV-1 gG and VZV gene 62 sequences in single cells recovered from sections of human trigeminal ganglia (TG) obtained at autopsy. Among 970 individual sensory neurons from five subjects, 2.0 to 10.5% were positive for HSV-1 DNA, with a median of 11.3 copies/positive cell, compared with 0.2 to 1.5% of neurons found to be positive by in situ hybridization (ISH) for HSV-1 latency-associated transcripts (LAT), the classical surrogate marker for HSV latency. This indicates a more pervasive latent HSV-1 infection of human TG neurons than originally thought. Combined ISH/LCM/PCR assays revealed that the majority of the latently infected neurons do not accumulate LAT to detectable levels. We detected VZV DNA in 1.0 to 6.9% of individual neurons from 10 subjects. Of the total 1,722 neurons tested, 4.1% were VZV DNA positive, with a median of 6.9 viral genomes/positive cell. After removal by LCM of all visible neurons on a slide, all surrounding nonneuronal cells were harvested and assayed: 21 copies of HSV-1 DNA were detected in similar to 5,200 nonneuronal cells, while nine VZV genomes were detected in similar to 14,200 nonneuronal cells. These data indicate that both HSV-1 and VZV DNAs persist in human TG primarily, if not exclusively, in a moderate percentage of neuronal cells. C1 NIAID, Med Virol Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. RP Wang, KN (reprint author), NIAID, Med Virol Sect, Lab Clin Infect Dis, NIH, Bldg 10,Room 11N-228,10 Ctr Dr, Bethesda, MD 20892 USA. EM kwang@niaid.nih.gov FU Intramural NIH HHS NR 59 TC 75 Z9 78 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 2005 VL 79 IS 22 BP 14079 EP 14087 DI 10.1128/JVI.79.22.14079-14087.2005 PG 9 WC Virology SC Virology GA 980ER UT WOS:000232997500024 PM 16254342 ER PT J AU Ono, A Waheed, AA Joshi, A Freed, EO AF Ono, A Waheed, AA Joshi, A Freed, EO TI Association of human immunodeficiency virus type 1 gag with membrane does not require highly basic sequences in the nucleocapsid: Use of a novel gag multimerization assay SO JOURNAL OF VIROLOGY LA English DT Article ID ROUS-SARCOMA-VIRUS; ASSEMBLY INTERMEDIATE COMPLEXES; GREEN FLUORESCENT PROTEIN; GPI-ANCHORED PROTEINS; C-TERMINAL DOMAIN; CELL-FREE SYSTEM; LIPID RAFTS; IN-VITRO; CAPSID PROTEIN; MATRIX PROTEIN AB Human immunodeficiency virus type 1 (HIV-1) particle production, a process driven by the Gag polyprotein precursor, occurs on the plasma membrane in most cell types. The plasma membrane contains cholesterol-enriched microdomains termed lipid rafts, which can be isolated as detergent-resistant membrane (DRM). Previously, we and others demonstrated that HIV-1 Gag is associated with DRM and that disruption of Gag-raft interactions impairs HIV-1 particle production. However, the determinants of Gag-raft association remain undefined. In this study, we developed a novel epitope-based Gag multimerization assay to examine whether Gag assembly is essential for its association with lipid rafts. We observed that membrane-associated, full-length Gag is poorly detected by immunoprecipitation relative to non-membrane-bound Gag. This poor detection is due to assembly-driven masking of Gag epitopes, as denaturation greatly improves immunoprecipitation. Gag mutants lacking the Gag-Gag interaction domain located in the N terminus of the nucleocapsid (NC) were efficiently immunoprecipitated without denaturation, indicating that the epitope masking is caused by higher-order Gag multimerization. We used this assay to examine the relationship between Gag assembly and Gag binding to total cellular membrane and DRM. Importantly, a multimerization-defective NC mutant displayed wild-type levels of membrane binding and DRM association, indicating that NC-mediated Gag multimerization is dispensable for association of Gag with membrane or DRM. We also demonstrate that different properties of sucrose and iodixanol membrane flotation gradients may explain some discrepancies regarding Gag-raft interactions. This report offers new insights into the association of HIV-1 Gag with membrane and with lipid rafts. C1 NCI, HIV Drug Resistance Program, Virus Cell Interact Sect, Frederick, MD 21701 USA. RP Ono, A (reprint author), Univ Michigan, Sch Med, Dept Microbiol & Immunol, 6706A Med Sci Bldg 2,, Ann Arbor, MI 48109 USA. EM akiraono@umich.edu OI Ono, Akira/0000-0001-7841-851X FU Intramural NIH HHS NR 100 TC 62 Z9 66 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 2005 VL 79 IS 22 BP 14131 EP 14140 DI 10.1128/JVI.79.22.14131-14140.2005 PG 10 WC Virology SC Virology GA 980ER UT WOS:000232997500030 PM 16254348 ER PT J AU Yamanegi, K Tang, S Zheng, ZM AF Yamanegi, K Tang, S Zheng, ZM TI Kaposi's sarcoma-associated herpesvirus K8 beta is derived from a spliced intermediate of K8 pre-mRNA and antagonizes K8 alpha (K-bZIP) to induce p21 and p53 and blocks K8 alpha-CDK2 interaction SO JOURNAL OF VIROLOGY LA English DT Article ID BINDING PROTEIN-ALPHA; MULTICENTRIC CASTLEMANS-DISEASE; REPLICATION-ASSOCIATED PROTEIN; NONSENSE-MEDIATED DECAY; EPSTEIN-BARR-VIRUS; CELL-CYCLE ARREST; DNA-REPLICATION; GENE-EXPRESSION; TERMINATION CODONS; IN-VITRO AB Kaposi's sarcoma-associated herpesvirus (KSHV) is a lymphotropic DNA tumor virus that induces Kaposi's sarcoma and AIDS-related primary effusion lymphoma. KSHV open reading frame 50 and K8 genes in early viral lytic infection express, respectively, a tricistronic and a bicistronic pre-mRNA, which undergo alternative splicing to create two major spliced mRNA isoforms, alpha and beta, by inclusion (beta) or exclusion (alpha) of an intron at nucleotides 75563 to 75645. This intron contains some suboptimal features, which cause the intron 5' splice site (ss) to interact weakly with U1 snRNA and the 3' ss to bind a U2 auxiliary factor, U2AF, with low affinity. Optimization of this intron in K8 (K8 intron 2) promoted the interaction of the 5' ss with U1 and the 3' ss with U2AF, resulting in a substantial increase in intron splicing. Splicing of K8 intron 2 has also been shown to be stimulated by the splicing of a downstream intron. This was confirmed by the insertion of a human P-globin intron into the K8 beta exon 3-exon 4 splice junction, which promoted splicing of K8 beta intron 2 and conversion of the K8 beta mRNA to the K8 alpha mRNA that encodes a K-bZIP protein. Intron 2 contains a premature termination codon, yet the K8 beta mRNA is insensitive to nonsense-mediated mRNA decay, suggesting that the truncated K8 beta protein may have a biological function. Indeed, although the truncated K8 beta protein is missing only a C-terminal leucine zipper domain from the K-bZIP, its expression antagonizes the ability of the K-bZIP to induce p53 and p21 and, blocks, K-bZIP-CDK2 interaction through interfering K8a mRNA production. C1 NCI, Ctr Canc Res, HIV & AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA. RP Zheng, ZM (reprint author), NCI, Ctr Canc Res, HIV & AIDS Malignancy Branch, NIH, 10 Ctr Dr,Rm 10 S255,MSC 1868, Bethesda, MD 20892 USA. EM zhengt@exchange.nih.gov RI Tang, Shuang/F-9115-2014 OI Tang, Shuang/0000-0002-3084-0903 FU Intramural NIH HHS; NCI NIH HHS [Z01 SC010357-06] NR 61 TC 15 Z9 16 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 2005 VL 79 IS 22 BP 14207 EP 14221 DI 10.1128/JVI.79.22.14207-14221.2005 PG 15 WC Virology SC Virology GA 980ER UT WOS:000232997500038 PM 16254356 ER PT J AU Sun, LL Finnegan, CM Kish-Catalone, T Blumenthal, R Garzino-Demo, P Maggiore, GML Berrone, S Kleinman, C Wu, ZB Abdelwahab, S Lu, WY Garzino-Demo, A AF Sun, LL Finnegan, CM Kish-Catalone, T Blumenthal, R Garzino-Demo, P Maggiore, GML Berrone, S Kleinman, C Wu, ZB Abdelwahab, S Lu, WY Garzino-Demo, A TI Human beta-defensins suppress human immunodeficiency virus infection: Potential role in mucosal protection SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN NEUTROPHIL DEFENSINS; HIV-1 INFECTION; ANTIMICROBIAL PEPTIDES; HUMAN BETA-DEFENSIN-3; ALPHA-DEFENSINS; DENDRITIC CELLS; HOST-DEFENSE; PANETH CELLS; IN-VITRO; EXPRESSION AB beta-Defensins are small (3 to 5 kDa in size) secreted antimicrobial and antiviral proteins that are components of innate immunity. beta-Defensins are secreted by epithelial cells, and they are expressed at high levels in several mucosae, including the mouth, where the concentration of these proteins can reach 100 mu g/ml. Because of these properties, we wondered whether they could be part of the defenses that lower oral transmission of human immunodeficiency virus (HIV) compared to other mucosal sites. Our data show that select beta-defensins, especially human beta-defensin 2 (hBD2) and hBD3, inhibit R5 and X4 HIV infection in a dose-dependent manner at doses that are compatible with or below those measured in the oral cavity. We observed that beta-defensin treatment inhibited accumulation of early products of reverse transcription, as detected by PCR. We could not, however, detect any reproducible inhibition of env-mediated fusion, and we did not observe any modulation of HIV coreceptors following treatment with hBD1 and hBD2, in both resting and phytohemagglutinin-activated cells. Our data instead suggest that, besides a direct inactivation of HIV virions, hBD2 inhibits HIV replication in the intracellular environment. Therefore, we speculate that beta-defensins mediate a novel antiretroviral mechanism that contributes to prevention of oral HIV transmission in the oral cavity. Imunnohistochemical data on hBD2 expression in oral mucosal tissue shows that hBD2 is constitutively expressed, forming a barrier layer across the epithelium in healthy subjects, while in HIV-positive subjects levels of hBD2 expression are dramatically diminished. This may predispose HIV-positive subjects to increased incidence of oral complications associated with HIV infection. C1 Univ Maryland, Inst Biotechnol, Div Basic Sci, Inst Human Virol, Baltimore, MD 21201 USA. NCI, Ctr Canc Res, Nanobiol Program, NIH, Frederick, MD 21702 USA. Univ Turin, S Giovanni Battista Hosp, Dept Maxillofacial Surg, Turin, Italy. RP Garzino-Demo, A (reprint author), Univ Maryland, Inst Biotechnol, Div Basic Sci, Inst Human Virol, Room S613,725 W Lombard St, Baltimore, MD 21201 USA. EM garzinod@umbi.umd.edu RI Lu, Wuyuan/B-2268-2010; Abdelwahab, Sayed/P-1481-2016; OI Abdelwahab, Sayed/0000-0002-9636-7485; Garzino Demo, Paolo/0000-0003-0462-2299 FU Intramural NIH HHS; NIAID NIH HHS [AI056264, R21 AI056264]; NIDCR NIH HHS [1R21DE15508-01, R21 DE015508] NR 65 TC 137 Z9 150 U1 1 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 2005 VL 79 IS 22 BP 14318 EP 14329 DI 10.1128/JVI.79.22.14318-14329.2005 PG 12 WC Virology SC Virology GA 980ER UT WOS:000232997500048 PM 16254366 ER PT J AU Warner, H AF Warner, H TI Biology for non-biologists: Use of model organisms to study SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Meeting Abstract CT 57th Annual Meeting of the Gerontological-Society-of-America CY NOV 19-23, 2004 CL Washington, DC SP Gerontol Soc Amer C1 NIA, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD NOV PY 2005 VL 60 IS 11 BP 1359 EP 1359 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 992ZZ UT WOS:000233923800002 ER PT J AU Maggio, D Cherubini, A Lauretani, F Russo, RC Bartali, B Pierandrei, M Ruggiero, C Macchiarulo, MC Giorgino, R Minisola, S Ferrucci, L AF Maggio, D Cherubini, A Lauretani, F Russo, RC Bartali, B Pierandrei, M Ruggiero, C Macchiarulo, MC Giorgino, R Minisola, S Ferrucci, L TI 25(OH)D serum levels decline with age earlier in women than in men and less efficiently prevent compensatory hyperparathyroidism in older adults SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID HORMONE REPLACEMENT THERAPY; VITAMIN-D INSUFFICIENCY; HYPOVITAMINOSIS-D; POSTMENOPAUSAL WOMEN; PARATHYROID-HORMONE; SUN PROTECTION; D DEFICIENCY; POPULATION; PREVALENCE; NUTRITION AB Background. Although a host of factors are known to influence 25-hydroxyvitamin D [25(OH)D] serum levels, few studies addressed the distinctive sex-specific influence of aging, and the age-specific relationship of parathyroid hormone (PTH) with 25(OH)D. The aims of this research were to evaluate changes of 25(OH)D and PTH levels with age in a large population-based sample of men and women and to test the hypothesis that 25(OH)D serum concentrations needed to offset age-associated hyperparathyroidism are significantly higher in older than in younger persons. Methods. In 1107 participants of the InCHIANTI (Invecchiare in Chianti, i.e., Aging in the Chianti area) study, we collected information on dietary intake, daylight exposure, and disability, and measured renal function and serum 25(OH)D and PTH. Results. In women, the age-related decline of 25(OH)D was already evident shortly after age 50, whereas in men it started only after age 70 and was substantially less steep. Age, daylight exposure, winter season, and disability were independent predictors of low 25(OH)D levels. For any given level of 25(OH)D, PTH levels were progressively and consistently higher in older than in younger participants. Conclusions. These findings suggest that the age-associated fall of serum 25(OH)D starts earlier in women than in men and that higher levels of 25(OH)D are required in older compared to younger persons to avoid the age-associated compensatory hyperparathyroidism.. C1 Univ Perugia, Monteluce Policlin, I-06122 Perugia, Italy. INRCA, Lab Clin Epidemiol, Dept Geriatr, Florence, Italy. Procter & Gamble Co, Rome, Italy. Univ Roma La Sapienza, Policlin Umberto I, Dept Clin Sci, Rome, Italy. NIH, Longitudinal Studies Sect, Clin Res Branch, Baltimore, MD USA. RP Maggio, D (reprint author), Univ Perugia, Monteluce Policlin, Via Brunamonti, I-06122 Perugia, Italy. EM dariomaggio1@tin.it RI Lauretani, Fulvio/K-5115-2016; OI Lauretani, Fulvio/0000-0002-5287-9972; Cherubini, Antonio/0000-0003-0261-9897 NR 40 TC 40 Z9 42 U1 0 U2 3 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD NOV PY 2005 VL 60 IS 11 BP 1414 EP 1419 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 992ZZ UT WOS:000233923800021 PM 16339327 ER PT J AU Hicks, GE Simonsick, EM Harris, TB Newman, AB Weiner, DK Nevitt, MA Tylavsky, FA AF Hicks, GE Simonsick, EM Harris, TB Newman, AB Weiner, DK Nevitt, MA Tylavsky, FA TI Trunk muscle composition as a predictor of reduced functional capacity in the health, aging and body composition study: The moderating role of back pain SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID LOWER-EXTREMITY PERFORMANCE; SKELETAL-MUSCLE; RISK-FACTORS; PHYSICAL FUNCTION; OLDER-ADULTS; WOMEN; STRENGTH; MASS; FAT; MEN AB Background. Cross-sectionally, lower trunk muscle attenuation (higher fat infiltration) has been associated with poorer physical function in older adults. We hypothesize that lower trunk muscle attenuation will be associated with lower functional capacity 3 years later and that back pain status will moderate this relationship. Methods. The study sample consisted of a biracial cohort of well functioning men (739) and women (788) aged 70-79 years from the Pittsburgh site of the Health, Aging and Body Composition (Health ABC) study. Computed tomography was used to measure trunk muscle area and attenuation of the lumbar paraspinal, lateral abdominal, and rectus abdominus muscles at baseline. The Health ABC Physical Performance Battery (usual and narrow walk, chair stands, and standing balance) was used to measure functional capacity at the first and fourth annual clinic visits. Results. Regardless of back pain status, average trunk muscle attenuation (but not muscle area) was positively associated with overall physical performance, particularly balance (p < .01), in a fully adjusted model. The association between trunk attenuation and functional capacity was significantly stronger in participants with at least moderate back pain in the year prior to baseline (p < .05 for interaction; attenuation X back pain). Participants with moderate to extreme back pain had a greater decline in function over time (p < .05). Conclusions. Older adults with poorer trunk muscle composition (higher fat infiltration) exhibit reduced functional capacity, especially balance, 3 years later. Improving trunk muscle composition may be an important yet overlooked approach to maintain function and potentially reduce balance impairments, particularly in persons with a history of back pain. C1 Univ Maryland, Sch Med, Dept Phys Therapy & Rehabil Sci, Baltimore, MD 21201 USA. NIH, Clin Res Branch, Baltimore, MD USA. NIH, Lab Epidemiol Demog & Biometry, Baltimore, MD USA. Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Div Geriatr Med, Pittsburgh, PA 15260 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Univ Tennessee, Dept Prevent Med, Memphis, TN USA. RP Hicks, GE (reprint author), Univ Maryland, Sch Med, Dept Phys Therapy & Rehabil Sci, 100 Penn St, Baltimore, MD 21201 USA. EM ghicks@som.umaryland.edu RI Newman, Anne B./C-6408-2013 OI Newman, Anne B./0000-0002-0106-1150 FU NIA NIH HHS [N01-AG-6-2103, N01-AG-6-2101, N01-AG-6-2106] NR 29 TC 56 Z9 58 U1 3 U2 8 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD NOV PY 2005 VL 60 IS 11 BP 1420 EP 1424 PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 992ZZ UT WOS:000233923800022 PM 16339328 ER PT J AU Dannefer, D Uhlenberg, P Foner, A Abeles, RP AF Dannefer, D Uhlenberg, P Foner, A Abeles, RP TI On the shoulders of a giant: The legacy of Matilda White Riley for gerontology SO JOURNALS OF GERONTOLOGY SERIES B-PSYCHOLOGICAL SCIENCES AND SOCIAL SCIENCES LA English DT Article ID SOCIAL-CHANGE; AGE; COHORT; LIFE AB The legacy of Matilda White Riley to the study of aging encompasses multiple disciplines and extends to multiple domains within these disciplines. Although her greatest intellectual legacy is in sociology, she presented a compelling vision of the need for other disciplines to consider the role of social forces in shaping both aging as an individual, lifelong process and age as a feature of culture and social systems. This article reviews Riley's theoretical contributions in four areas: (1) articulating age and social systems; (2) identifying fallacies in the interpretation of research on aging; (3) theorizing about social change and structural lag; and (4) presenting social possibilities related to age integration. We conclude by considering briefly the reach of her legacy beyond sociology-in collaborating across disciplinary boundaries, in encouraging the development of sound longitudinal data archives, and in developing an institutional infrastructure to support and sustain research on aging in the social and behavioral sciences. Although short of physical stature, Riley's contributions to gerontology are enormous. Gerontologists from many disciplinary backgrounds have been informed by and rely upon these insights and thus share the advantage of "standing on the shoulders of a giant." C1 Case Western Reserve Univ, Cleveland, OH 44106 USA. Univ N Carolina, Chapel Hill, NC USA. Rutgers State Univ, New Brunswick, NJ 08903 USA. NIH, Bethesda, MD USA. RP Dannefer, D (reprint author), Case Western Reserve Univ, Cleveland, OH 44106 USA. EM dale.dannerfer@case.edu NR 54 TC 6 Z9 6 U1 1 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5014 J9 J GERONTOL B-PSYCHOL JI J. Gerontol. Ser. B-Psychol. Sci. Soc. Sci. PD NOV PY 2005 VL 60 IS 6 BP S296 EP S304 PG 9 WC Geriatrics & Gerontology; Gerontology; Psychology; Psychology, Multidisciplinary SC Geriatrics & Gerontology; Psychology GA 980GU UT WOS:000233003400009 PM 16260711 ER PT J AU Machado, MO Hirata, RDC Sellitti, DF Iotti, R Iotti, A Cusumano, AM Riordan, GP Coschigano, KT Kopchick, JJ Zuhl, I Nguyen, N Hirata, MH Doi, SQ AF Machado, MO Hirata, RDC Sellitti, DF Iotti, R Iotti, A Cusumano, AM Riordan, GP Coschigano, KT Kopchick, JJ Zuhl, I Nguyen, N Hirata, MH Doi, SQ TI Growth hormone promotes glomerular lipid accumulation in bGH mice SO KIDNEY INTERNATIONAL LA English DT Article DE glomerulosclerosis; cholesterol; triglycerides; HMG-CoA reductase; low-density lipoprotein receptor; scavenger receptor; real time RT-PCR ID LOW-DENSITY-LIPOPROTEIN; DIET-INDUCED HYPERCHOLESTEROLEMIA; HUMAN MESANGIAL CELLS; CHRONIC-RENAL-FAILURE; TRANSGENIC MICE; FACTOR-I; FOCAL GLOMERULOSCLEROSIS; CHOLESTEROL-METABOLISM; RECEPTOR EXPRESSION; SCAVENGER RECEPTOR AB Background. Bovine growth hormone (bGH) transgenic mice develop progressive glomerulosclerosis and exhibit abnormalities in hepatic lipid metabolism. We have previously shown that growth hormone up-regulates the low-density lipoprotein (LDL) receptor and 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) in mouse mesangial cells. However, a role of lipid abnormalities in bGH kidney disease has not yet been demonstrated. Methods. Groups of bGH mice (5 and 11 months old) presenting with, respectively, moderate and severe degrees of glomerulosclerosis were compared to age-matched controls. Neutral lipid content in kidney cortex was determined by oil red-O staining, serum cholesterol, and triglycerides by enzymatic assays, relative mRNA expression of LDL receptors, HMGR, and scavenger receptor by real-time reverse transcription-polymerase chain reaction (RT-PCR), and HMGR protein expression by immunoblotting. Two younger (5 and 12 weeks old) groups of mice were used to study scavenger receptor expression at earlier time points. Results. Serum cholesterol was significantly increased in bGH mice at 5 months, but triglycerides were lower than control levels at both 5 and 11 months. Renal cortex HMGR expression was elevated at the mRNA but not at the protein level in the 11-month-old bGH group compared to controls. However, glomerular neutral lipid staining and scavenger receptor mRNA expression were markedly increased in all bGH mice, including those at 5 weeks of age compared to respective controls. Conclusion. The bGH mouse exhibits an increased mesangial lipid content and elevated scavenger receptor mRNA expression as early as at 5 weeks of age, suggesting that an increased kidney uptake of oxidized LDL could play a role in the development of glomerulosclerosis in this mouse model. C1 Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. Univ Sao Paulo, Sch Pharmaceut Sci, Sao Paulo, Brazil. CEMIC, Dept Pathol, Buenos Aires, DF, Argentina. CEMIC, Nephrol Sect, Buenos Aires, DF, Argentina. NIDCD, Sect Struct Cell Biol, NIH, Bethesda, MD USA. Ohio Univ, Edison Biotechnol Inst, Athens, OH 45701 USA. Ohio Univ, Dept Biomed Sci, Coll Osteopath Med, Athens, OH 45701 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. RP Doi, SQ (reprint author), Uniformed Serv Univ Hlth Sci, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM sdoi@usush.mil RI Hirata, Rosario/A-7284-2011; Hirata, Mario/C-9718-2013 NR 51 TC 11 Z9 13 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD NOV PY 2005 VL 68 IS 5 BP 2019 EP 2028 DI 10.1111/j.1523-1755.2005.00656.x PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 971MQ UT WOS:000232388800038 PM 16221202 ER PT J AU Chu, WS Liang, Q Liu, JL Wei, MQ Winters, M Liotta, L Sandberg, G Gong, MK AF Chu, WS Liang, Q Liu, JL Wei, MQ Winters, M Liotta, L Sandberg, G Gong, MK TI A nondestructive molecule extraction method allowing morphological and molecular analyses using a single tissue section SO LABORATORY INVESTIGATION LA English DT Article DE molecule extraction; tissue section; immunohistochemistry; pathological diagnosis; molecular analysis ID PARAFFIN-EMBEDDED TISSUE; MODELING FORMALIN FIXATION; ANTIGEN RETRIEVAL; PCR AMPLIFICATION; CROSS-LINKING; SPECIMENS; PROTEINS; CANCER; HEAT; RNA AB In clinical practice, molecular analysis of tumor specimens is often restricted by available technology for sample preparation. Virtually all current methods require homogenization of tissues for molecule extraction. We have developed a simple, rapid, nondestructive molecule extraction (NDME) method to extract proteins and nucleic acids directly from a single fixed or frozen tissue section without destroying the tissue morphology. The NDME method is based upon exposure of micron-thick tissue section to extraction buffer with the help of heating and/or intact physical forces ( ultrasound and microwave) to facilitate release of macromolecules into the buffer. The extracted proteins and nucleic acids can be used directly without further purification for downstream SDS-PAGE analysis, immunoblotting, protein array, mass spectra protein profiling, PCR, and RTPCR reactions. Most importantly, the NDME procedure also serves as an antigen retrieval treatment, so that after NDME, the same tissue section can be used for histopathological analyses, such as H&E staining, immunohistochemistry, and in situ hybridization. Thus, the NDME method allows, for the first time, both histological diagnosis and molecular analysis on a single tissue section, whether it is from frozen or fixed tissue specimens. C1 Armed Forces Inst Pathol, Dept Sci Labs, Washington, DC 20306 USA. NCI, Proteom Lab, Pathol Lab, NIH, Bethesda, MD 20892 USA. Bioquick Inc, Silver Spring, MD USA. RP Chu, WS (reprint author), Armed Forces Inst Pathol, Dept Sci Labs, Washington, DC 20306 USA. EM chu@afip.osd.mil FU NCI NIH HHS [1R21 CA091166-01A1] NR 31 TC 49 Z9 49 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD NOV PY 2005 VL 85 IS 11 BP 1416 EP 1428 DI 10.1038/labinvest.3700337 PG 13 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 977MJ UT WOS:000232807600010 PM 16127423 ER PT J AU Hurd, SS Lenfant, C AF Hurd, SS Lenfant, C TI COPD: good lung health is the key SO LANCET LA English DT Editorial Material C1 Global Initiat Chron Obstruct Lung Dis, Gaithersburg, MD 20883 USA. NHLBI, NIH, Bethesda, MD 20892 USA. RP Hurd, SS (reprint author), Global Initiat Chron Obstruct Lung Dis, Gaithersburg, MD 20883 USA. EM shurd@prodigy.net NR 8 TC 4 Z9 5 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 NOV-DEC PY 2005 VL 366 IS 9500 BP 1832 EP 1834 DI 10.1016/S0140-6736(05)67634-9 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 988ZR UT WOS:000233643200006 PM 16310538 ER PT J AU Dunn, DT Gibb, DM Duong, T Babiker, AG Aboulker, IP Bulterys, M Cortina-Borja, M Gabiano, C Galli, L Giaquinto, C Harris, DR Hughes, M McKinney, R Moye, J Newell, ML Pahwa, S Palumbo, P Rudin, C Sharland, M Shearer, W Thompson, B Tookey, P AF Dunn, DT Gibb, DM Duong, T Babiker, AG Aboulker, IP Bulterys, M Cortina-Borja, M Gabiano, C Galli, L Giaquinto, C Harris, DR Hughes, M McKinney, R Moye, J Newell, ML Pahwa, S Palumbo, P Rudin, C Sharland, M Shearer, W Thompson, B Tookey, P CA HIV Paediat Prognostic Markers Col TI Use of total lymphocyte count for informing when to start antiretroviral therapy in HIV-infected children: a meta-analysis of longitudinal data SO LANCET LA English DT Article ID RESOURCE-LIMITED SETTINGS; HIV-1-INFECTED CHILDREN; DISEASE PROGRESSION; AFRICAN CHILDREN; POOR SETTINGS; CD4; AGE; MORTALITY; ZIDOVUDINE; SUBSETS AB Background Total lymphocyte count has been proposed as an alternative to the percentage of CD4+ T-cells to indicate when antiretroviral therapy should be started in children with HIV in resource-poor settings. We aimed to assess thresholds of total lymphocyte count at which antiretroviral therapy should be considered, and compared monitoring of total lymphocyte count with monitoring of CD4-cell percentage. Methods Longitudinal data on 3917 children with HIV infection were pooled from observational and randomised studies in Europe and the USA. The 12-month risks of death and AIDS by most recent total lymphocyte count and age were estimated by parametric survival models, based on measurements before antiretroviral therapy or during zidovudine monotherapy. Risks were derived and compared at thresholds of total lymphocyte count and CD4-cell percentage for starting antiretroviral therapy recommended in WHO 2003 guidelines. Findings Total lymphocyte count was a powerful predictor of the risk of disease progression despite a weak correlation with CD4-cell percentage (r=0.08-0.19 dependent on age). For children older than 2 years, the 12-month risk of death and AIDS increased sharply at values less than 1500-2000 cells per mu L, with little trend at higher values. Younger children had higher risks and total lymphocyte count was less prognostic. Mortality risk was substantially higher at thresholds of total lymphocyte count recommended by WHO than at corresponding thresholds of CD4-cell percentage. When the markers were compared at the threshold values at which mortality risks were about equal, total lymphocyte count was as effective as CD4-cell percentage for identifying children before death, but resulted in an earlier start of antiretroviral therapy. Interpretation In this population, total lymphocyte count was a strong predictor of short-term disease progression, being only marginally less predictive than CD4-cell percentage. Confirmatory studies in resource-poor settings are needed to identify the most cost-effective markers to guide initiation of antiretroviral therapy. C1 MRC, Clin Trials Unit, London NW1 2DA, England. INSERM, SC10, F-75654 Paris, France. Ctr Dis Control & Prevent, Div HIV AIDS Prevent, Atlanta, GA USA. UCL, Inst Child Hlth, London, England. Univ Turin, Dept Paediat, Turin, Italy. Univ Florence, Dept Paediat, Florence, Italy. Univ Padua, Dept Paediat, Padua, Italy. Westat Corp, Rockville, MD 20850 USA. NICHD, Intravenous Immunoglobulin Study Grp, Bethesda, MD 20892 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Duke Univ, Med Ctr, Durham, NC USA. NICHD, NIH, Rockville, MD USA. NICHD, Women & Infants Transmiss Study, Bethesda, MD 20892 USA. N Shore LIJ Res Inst, Manhasset, NY USA. UMDNJ Med Sch, Newark, NJ USA. Univ Childrens Hosp, Basel, Switzerland. Univ London St Georges Hosp, Sch Med, London SW17 0RE, England. Baylor Coll Med, Houston, TX 77030 USA. Clin Trials & Surveys Corp, Baltimore, MD USA. RP Dunn, DT (reprint author), MRC, Clin Trials Unit, 222 Euston Rd, London NW1 2DA, England. EM d.dunn@ctu.mrc.ac.uk RI Tookey, Pat /G-2732-2010; SHCS, int. coll. B/G-4090-2011; Cortina Borja, Mario/A-3847-2009; SHCS, all/G-4072-2011 OI Tookey, Pat /0000-0001-6258-0387; NR 29 TC 29 Z9 29 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD NOV-DEC PY 2005 VL 366 IS 9500 BP 1868 EP 1874 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 988ZR UT WOS:000233643200025 ER PT J AU Launer, LJ AF Launer, LJ TI Regional differences in rates of dementia: MRC-CFAS SO LANCET NEUROLOGY LA English DT Editorial Material ID ATHEROSCLEROSIS; DISEASE C1 NIA, LEDB, IRP, Bethesda, MD USA. RP Launer, LJ (reprint author), NIA, LEDB, IRP, Bethesda, MD USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1474-4422 J9 LANCET NEUROL JI Lancet Neurol. PD NOV PY 2005 VL 4 IS 11 BP 694 EP 695 DI 10.1016/S1474-4422(05)70206-4 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 980GK UT WOS:000233002400005 PM 16239175 ER PT J AU Panlilio, LV Weiss, SJ AF Panlilio, LV Weiss, SJ TI Sensory modality and stimulus control in the pigeon: Cross-species generality of single-incentive selective-association effects SO LEARNING AND MOTIVATION LA English DT Article DE constraints on learning; selective associations; stimulus-reinforcer interactions; appetitive-aversive; interactions; avoidance; food; shock; pigeons ID REINFORCER INTERACTION; SHOCK; RAT; CONSTRAINTS; DOMINANCE; ATTENTION; BLOCKING AB In earlier studies with rats, the effectiveness of the auditory element of a tone-light discriminative stimulus was enhanced when the conditioned incentive value of the compound was negative rather than positive. The present experiment systematically replicated these results in pigeons trained to press a treadle in the presence of a tone-light compound under food-reinforcement or shock-avoidance schedules. Positive incentive value was conditioned to the compound by associating it with either food or relative safety from shock. The compound was made negative in other groups by associating it with shock or the absence of food. When tone and light were presented separately following this training, control by the auditory element was significantly enhanced in the conditions designed to make the compound negative rather than positive. The similarity of this constraint on learning in rats and pigeons suggests that it involves a fundamental attentional and incentive-motivational process with widespread species generality. Published by Elsevier Inc. C1 NIDA, Intramural Res Program, Baltimore, MD USA. American Univ, Dept Psychol, Washington, DC 20016 USA. RP Panlilio, LV (reprint author), NIDA, Intramural Res Program, 5500 Nathan Shock Dr, Baltimore, MD USA. EM lpanlili@irp.nida.nih.gov NR 23 TC 2 Z9 2 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0023-9690 J9 LEARN MOTIV JI Learn. Motiv. PD NOV PY 2005 VL 36 IS 4 BP 408 EP 424 DI 10.1016/j.lmot.2004.11.007 PG 17 WC Psychology, Biological; Psychology, Experimental SC Psychology GA 986YT UT WOS:000233486300003 ER PT J AU Dou, JT Chen, M Dufour, F Alkon, DL Zhao, WQ AF Dou, JT Chen, M Dufour, F Alkon, DL Zhao, WQ TI Insulin receptor signaling in long-term memory consolidation following spatial learning SO LEARNING & MEMORY LA English DT Article ID HIPPOCAMPAL SYNAPTIC PLASTICITY; MAP KINASE CASCADE; GENE-EXPRESSION; WATER MAZE; ALZHEIMERS-DISEASE; AMPA RECEPTORS; DIABETIC RATS; BRAIN; NEURONS; INTERNALIZATION AB Evidence has shown that the insulin and insulin receptor [IR) play a role in cognitive function. However, the detailed mechanisms underlying insulin's action on learning and memory are not yet understood. Here we investigated changes in long-term memory-associated expression of the IR and downstream molecules in the rat hippocampus. After long-term memory consolidation following a water maze learning experience, gene expression of IR showed an up-regulation in the CA1, but a down-regulation in the CA3 region. These were correlated with a significant reduction in hippocampal IR protein levels. Learning-specific increases in levels of downstream molecules Such as IRS-1 and Akt were detected in the synaptic membrane accompanied by decreases in Akt phosphorylation. Translocation of Shc protein to the synaptic membrane and activation of Erk1/2 were also observed after long-term memory formation. Despite the clear memory-correlated alterations in IR signaling pathways, insulin deficits in experimental diabetes mellitus [DM) rats induced by intraperitoneal injections of streptozotocin resulted in only minor memory impairments. This may be due to higher glucose levels in the DM brain, and to compensatory mechanisms from other signaling pathways Such as the insulin-like growth factor-1 receptor (IGF-1R) system. Our results suggest that insulin/1R signaling plays a modulatory role in learning and memory processing, which may be compensated for by alternative pathways in the brain when an insulin deficit occurs. C1 Blanchette Rockefeller Neurosci Inst, Rockville, MD 20850 USA. Northwestern Univ, Dept Neurobiol & Physiol, Evanston, IL 60208 USA. NIDDK, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. Peoples Liberat Army Gen Hosp, Dept Endocrinol, Beijing 100853, Peoples R China. RP Zhao, WQ (reprint author), Blanchette Rockefeller Neurosci Inst, Rockville, MD 20850 USA. EM w-zhao@northwestern.edu NR 46 TC 90 Z9 97 U1 0 U2 5 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 1072-0502 J9 LEARN MEMORY JI Learn. Mem. PD NOV-DEC PY 2005 VL 12 IS 6 BP 646 EP 655 DI 10.1101/lm.88005 PG 10 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 989RY UT WOS:000233692700016 PM 16287721 ER PT J AU Hu, XR Bies, J Wolff, L AF Hu, XR Bies, J Wolff, L TI Interferon beta increases c-Myc proteolysis in mouse monocyte/macrophage leukemia cells SO LEUKEMIA RESEARCH LA English DT Article DE interferon; c-Myc; proteolysis; leukemia; cytokine; growth arrest ID DAUDI CELLS; IN-VIVO; PROTEIN-DEGRADATION; GENE-EXPRESSION; G0/G1 ARREST; CYCLE; PROTEASOME; INHIBITORS; MUTATIONS; ALPHA AB Growth inhibitory activity of interferons (IFNs) has been attributed to several events. These include rapid induction of cyclin-dependent kinase inhibitors, such as those in the Cip/Kip and lnk4 families and clown-regulation of c-myc mRNA and c-Myc transcriptional activity. Here, we report an additional mechanism, involving regulation of Myc protein levels, through which type 1 IFN may halt proliferation of cells. This was discovered using a cell line which constitutively expresses c-myc from a retrovirus vector and which was reported to have undergone deletion of genes encoding the Ink4 tumor suppressors p15 and p16. IFN beta caused a reduction in the steady state level of c-Myc protein by increasing degradation through the 26S proteasome. Our data, as well as that of others, indicate that multiple levels of c-Myc expression can be affected by IFN treatment and this contributes to rapid growth arrest in the G1 phase of the cell cycle. Published by Elsevier Ltd. C1 NCI, Leukemogenesis Sect, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA. RP Wolff, L (reprint author), Bldg 37,Room 4124,37 Convent Dr,MSC 4263, Bethesda, MD 20892 USA. EM lwolff@helix.nih.gov NR 30 TC 4 Z9 5 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2126 J9 LEUKEMIA RES JI Leuk. Res. PD NOV PY 2005 VL 29 IS 11 BP 1307 EP 1314 DI 10.1016/j.leukres.2005.04.002 PG 8 WC Oncology; Hematology SC Oncology; Hematology GA 969OE UT WOS:000232242800013 PM 15939469 ER PT J AU Maoz, D Lee, HJ Deutsch, J Rapoport, SI Bazinet, RP AF Maoz, D Lee, HJ Deutsch, J Rapoport, SI Bazinet, RP TI Immediate no-flow ischemia decreases rat heart nonesterified fatty acid and increases acyl-CoA species concentrations SO LIPIDS LA English DT Article ID COENZYME-A ESTERS; K-ATP CHANNELS; ARACHIDONIC-ACID; BRAIN PHOSPHOLIPIDS; MICROWAVE FIXATION; CANINE MYOCARDIUM; ACETYL-COA; METABOLISM; ACCUMULATION; DECAPITATION AB Tissues changes in FA metabolism can occur quite rapidly in response to ischemia and may require immediate microwave fixation to determine basal concentrations. The present study aimed to quantify the effects of immediate no-flow ischemia on concentrations of individual nonesterified FA (NEFA) and acyl-CoA species in the rat heart. Male CDF 344 rats were anesthetized and decapitated either 5 min prior to being microwaved (5.5 kW, 3.4 s, twice) to produce ischemia or microwaved prior to decapitation (nonischemic). Hearts were then removed and used to measure the concentrations of acyl-CoA species and FA in several lipid classes. The ischemic heart total NEFA concentration was significantly lower than that in the nonischemic heart (11.9 vs. 19.0 nmol/g). Several individual NEFA concentrations were decreased by 31-85%. Ischemic heart total long-chain acyl-CoA concentrations (21.0 nmol/g) were significantly higher than those in nonischemic hearts (11.4 nmol/g). Increased concentrations of individual acyl-CoA species occurred in palmitoyl-CoA, stearoyl-CoA, oleoyl-CoA, and linoleoyl-CoA. Concentrations of short-chain acetyl-CoA and beta-hydroxy-beta-methylglutaryl-CoA were also two- to three-fold higher in ischemic hearts than in nonischemic hearts. The FA concentration in TG and phospholipids generally did not differ between the groups. Decreases in concentrations of individual FA and increases in acyl-CoA species during no-flow ischemia occur very rapidly within the heart. Although it is not clear how these alterations contribute to the pathogenesis of ischemia, it is evident that future studies attempting to quantify basal levels of these metabolites could use microwave fixation. C1 NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. Hebrew Univ Jerusalem, Sch Pharm, Dept Med Chem, David R Bloom Ctr Pharm, IL-91120 Jerusalem, Israel. RP Bazinet, RP (reprint author), NIA, Brain Physiol & Metab Sect, NIH, 9000 Rockville Pike,Bldg 9,Rm 1s 126, Bethesda, MD 20892 USA. EM rbazinet@mail.nih.gov NR 55 TC 5 Z9 6 U1 0 U2 0 PU AMER OIL CHEMISTS SOC A O C S PRESS PI CHAMPAIGN PA 221 W BRADLEY AVE, CHAMPAIGN, IL 61821-1827 USA SN 0024-4201 J9 LIPIDS JI Lipids PD NOV PY 2005 VL 40 IS 11 BP 1149 EP 1154 DI 10.1007/s11745-005-1479-9 PG 6 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA 997JW UT WOS:000234242500007 PM 16459927 ER PT J AU Granone, P Margaritora, S Porziella, V Trodella, L D'Angelilo, RM Ramella, S Russo, P Cesario, A AF Granone, P Margaritora, S Porziella, V Trodella, L D'Angelilo, RM Ramella, S Russo, P Cesario, A TI Comment on "Post-operative radiotherapy in non small cell lung cancer: update of individual patient data" [Lung Cancer 2005;47(1): 81-83] SO LUNG CANCER LA English DT Letter ID METAANALYSIS; STAGE C1 Catholic Univ Rome, Div Gen Thorac Surg, Rome, Italy. Catholic Univ Rome, Dept Radiotherapy, Rome, Italy. Biomed Univ, Dept Radiotherapy, Rome, Italy. Natl Canc Inst, DOMI, Lab Translat Res B Lung Canc, Genoa, Italy. Catholic Univ, Div Gen Thorac Surg, I-00168 Rome, Italy. IRCCS, Clin Resp Pathol Translat Lab, Rome, Italy. RP Cesario, A (reprint author), Catholic Univ Rome, Div Gen Thorac Surg, Rome, Italy. EM atfcesario@rm.unicatt.it RI CESARIO, Alfredo/O-4215-2015; OI CESARIO, Alfredo/0000-0003-4687-0709; D'Angelillo, Rolando M./0000-0003-3636-6429; Ramella, Sara/0000-0002-5782-7717 NR 6 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD NOV PY 2005 VL 50 IS 2 BP 277 EP 278 DI 10.1016/j.lungcan.2005.04.015 PG 2 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 979VR UT WOS:000232973600018 PM 16076510 ER PT J AU Wilbur, WJ Yeganova, L Kim, W AF Wilbur, WJ Yeganova, L Kim, W TI The synergy between PAV and AdaBoost SO MACHINE LEARNING LA English DT Article DE boosting; isotonic regression; convergence; document classification; k nearest neighbors ID LOGISTIC-REGRESSION; ALGORITHMS; MARGINS AB Schapire and Singer's improved version of AdaBoost for handling weak hypotheses with confidence rated predictions represents an important advance in the theory and practice of boosting. Its success results from a more efficient use of information in weak hypotheses during updating. Instead of simple binary voting a weak hypothesis is allowed to vote for or against a classification with a variable strength or confidence. The Pool Adjacent Violators (PAV) algorithm is a method for converting a score into a probability. We show how PAV may be applied to a weak hypothesis to yield a new weak hypothesis which is in a sense an ideal confidence rated prediction and that this leads to an optimal updating for AdaBoost. The result is a new algorithm which we term PAV-AdaBoost. We give several examples illustrating problems for which this new algorithm provides advantages in performance. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Wilbur, WJ (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM wilbur@ncbi.nlm.nih.gov NR 33 TC 5 Z9 5 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0885-6125 J9 MACH LEARN JI Mach. Learn. PD NOV PY 2005 VL 61 IS 1-3 BP 71 EP 103 DI 10.1007/s10994-005-1123-6 PG 33 WC Computer Science, Artificial Intelligence SC Computer Science GA 990XH UT WOS:000233776200003 ER PT J AU Gu, H Stein, EA Yang, YH AF Gu, H Stein, EA Yang, YH TI Nonlinear responses of cerebral blood volume, blood flow and blood oxygenation signals during visual stimulation SO MAGNETIC RESONANCE IMAGING LA English DT Article DE nonlinearity; cerebral blood volume; cerebral blood flow; blood oxygenation; functional MRI ID FUNCTIONAL MRI; BOLD RESPONSE; BRAIN ACTIVATION; IMPULSE-RESPONSE; HUMAN V1; FMRI; DYNAMICS; CORTEX AB Hemodynamic-based functional magnetic resonance imaging (fMRI) techniques provide a great utility for noninvasive functional brain mapping. However, because the hemodynamic signals reflect underlying neural activity indirectly, characterization of these signals following brain activation is essential for experimental design and data interpretation. In this report, the linear (or nonlinear) responses to neuronal activation of three hemodynamic parameters based primarily on changes of cerebral blood volume, blood flow and blood oxygenation were investigated by testing these hemodynamic responses' additivity property. Using a recently developed fMRI technique that acquires vascular space occupancy (VASO), arterial spin labeling (ASL) perfusion and blood oxygenation level-dependent (BOLD) signals simultaneously, the additivity property of the three hemodynamic responses in human visual cortex was assessed using various visual stimulus durations. Experiments on healthy volunteers showed that all three hemodynamic-weighted signals responded nonlinearly to stimulus durations less than 4 s, with the degree of nonlinearity becoming more severe as the stimulus duration decreased. Vascular space occupancy and ASL perfusion signals showed similar nonlinearity properties, whereas the BOLD signal was the most nonlinear. These data suggest that caution should be taken in the interpretation of hemodynamic-based signals in fMRI. Published by Elsevier Inc. C1 Natl Inst Drug Abuse, Neuroimaging Res Branch, NIH, Baltimore, MD 21224 USA. RP Yang, YH (reprint author), Natl Inst Drug Abuse, Neuroimaging Res Branch, NIH, Baltimore, MD 21224 USA. EM yihongyang@intra.nida.nih.gov RI Stein, Elliot/C-7349-2008 NR 20 TC 25 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 0730-725X J9 MAGN RESON IMAGING JI Magn. Reson. Imaging PD NOV PY 2005 VL 23 IS 9 BP 921 EP 928 DI 10.1016/j.mri.2005.09.007 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 996BE UT WOS:000234148600003 PM 16310107 ER PT J AU Karmakar, P Bohr, VA AF Karmakar, P Bohr, VA TI Cellular dynamics and modulation of WRN protein is DNA damage specific SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Article DE DNA damage; DNA repair; WRN distribution; phosphorylation of WRN; acetylation of WRN ID WERNER-SYNDROME PROTEIN; NUCLEOTIDE EXCISION-REPAIR; IN-VIVO; REPLICATION ARREST; MRE11 COMPLEX; NUCLEAR FOCI; S-PHASE; HELICASE; PHOSPHORYLATION; TRANSCRIPTION AB The human premature aging protein Werner (WRN), deficient in Werner syndrome (WS), is localized mainly to the nucleolus in many cell types. DNA damage or replication arrest causes WRN to redistribute from the nucleolus to the nucleoplasm into discrete foci. In this study, we have investigated DNA damage specific cellular redistribution of WRN. In response to agents causing DNA double strand breaks or DNA base damage, WRN is re-distributed from the nucleolus to the nucleoplasm in a reversible manner. However, after ultraviolet (UV) irradiation such redistribution of WRN is largely absent. We also show that WRN is associated with the insoluble protein fraction of cells after exposure to various kinds of DNA damage but not after UV irradiation. Further, we have studied the DNA damage specific post-translational modulation of WRN. Our results show that WRN is acetylated after mytomycin C or methyl methane-sulfonate treatment, but not after UV irradiation. Also, DNA damage specific phosphorylation of WRN is absent in UV irradiated cells. Inhibition of phosphorylation fails to restore WRN localization. Thus, our results suggest that the dynamics of WRN protein trafficking is DNA damage specific and is related to its post-translational modulation. The results also indicate a preferred role of WRN in recombination and base excision repair rather than nucleotide excision repair. Published by Elsevier Ireland Ltd. C1 NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. RP Bohr, VA (reprint author), NIA, Lab Mol Gerontol, NIH, 5600 Nathan Shock Dr,Box 1, Baltimore, MD 21224 USA. EM bohrv@grc.nia.nih.gov NR 37 TC 37 Z9 37 U1 2 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0047-6374 J9 MECH AGEING DEV JI Mech. Ageing Dev. PD NOV PY 2005 VL 126 IS 11 BP 1146 EP 1158 DI 10.1016/j.mad.2005.06.004 PG 13 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 978BI UT WOS:000232846800002 PM 16087220 ER PT J AU Stinstra, JG Shome, S Hopenfeld, B MacLeod, RS AF Stinstra, JG Shome, S Hopenfeld, B MacLeod, RS TI Modelling passive cardiac conductivity during ischaemia SO MEDICAL & BIOLOGICAL ENGINEERING & COMPUTING LA English DT Article DE conductivity; cardiac tissue; bidomain; ischaemia; cardiac modelling; gap junctions ID VENTRICULAR-ARRHYTHMIAS; SUBENDOCARDIAL ISCHEMIA; EPICARDIAL POTENTIALS; MYOCARDIAL-ISCHEMIA; PORCINE HEART; CELL PAIRS; RABBIT; CONNEXIN43; MUSCLE; VOLUME AB The results of a geometric model of cardiac tissue, used to compute the bidomain conductivity tensors during three phases of ischaemia, are described. Ischaemic conditions were simulated by model parameters being changed to match the morphological and electrical changes of three phases of ischaemia reported in literature. The simulated changes included collapse of the interstitial space, cell swelling and the closure of gap junctions. The model contained 64 myocytes described by 2 million tetrahedral elements, to which an external electric field was applied, and then the finite element method was used to compute the associated current density. In the first case, a reduction in the amount of interstitial space led to a reduction in extracellular longitudinal conductivity by about 20%, which is in the range of reported literature values. Moderate cell swelling in the order of 10-20% did not affect extracellular conductivity considerably. To match the reported drop in total tissue conductance reported in experimental studies during the third phase of ischaemia, a ten fold increase in the gap junction resistance was simulated. This ten-fold increase correlates well with the reported changes in gap junction densities in the literature. C1 Univ Utah, Sci Comp & Imaging Inst, Salt Lake City, UT 84112 USA. Univ Utah, Cardiovasc Res & Training Inst, Salt Lake City, UT USA. NHLBI, NIH, Bethesda, MD 20892 USA. Univ Utah, Dept Bioengn, Salt Lake City, UT USA. RP Stinstra, JG (reprint author), Univ Utah, Sci Comp & Imaging Inst, Salt Lake City, UT 84112 USA. EM jeroen@cvrti.utah.edu FU NHLBI NIH HHS [P20 HL68566-01] NR 29 TC 17 Z9 17 U1 0 U2 0 PU PETER PEREGRINUS LTD PI HERTS PA MICHAEL FARADAY HOUSE, SIX HILLS WAY, STEVANAGE, HERTS SG1 2AY, ENGLAND SN 0140-0118 J9 MED BIOL ENG COMPUT JI Med. Biol. Eng. Comput. PD NOV PY 2005 VL 43 IS 6 BP 776 EP 782 DI 10.1007/BF02430957 PG 7 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Mathematical & Computational Biology; Medical Informatics SC Computer Science; Engineering; Mathematical & Computational Biology; Medical Informatics GA 025PB UT WOS:000236277700013 PM 16594306 ER PT J AU O'Hanlon, TP Carrick, DM Arnett, FC Reveille, JD Carrington, M Gao, XJ Oddis, CV Morel, PA Malley, JD Malley, K Dreyfuss, J Shamim, EA Rider, LG Chanock, SJ Foster, CB Bunch, T Plotz, PH Love, LA Miller, FW AF O'Hanlon, TP Carrick, DM Arnett, FC Reveille, JD Carrington, M Gao, XJ Oddis, CV Morel, PA Malley, JD Malley, K Dreyfuss, J Shamim, EA Rider, LG Chanock, SJ Foster, CB Bunch, T Plotz, PH Love, LA Miller, FW TI Immunogenetic risk and protective factors for the idiopathic inflammatory myopathies - Distinct HLA-A, -B, -Cw,-DRB1 and -DQA1 allelic profiles and motifs define clinicopothologic groups in Caucasians SO MEDICINE LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; INCLUSION-BODY MYOSITIS; SYSTEMIC-LUPUS-ERYTHEMATOSUS; GENE-EXPRESSION DATA; RHEUMATOID-ARTHRITIS; AUTOIMMUNE-DISEASE; ETHNIC-GROUPS; HAPLOTYPE; CLASSIFICATION; ASSOCIATION AB The idiopathic inflammatory myopathies (IIM) are systemic connective tissue diseases in which autoimmune pathology is suspected to promote chronic muscle inflammation and weakness. We have performed low to high resolution genotyping to characterize the allelic profiles of HLA-A, -B, -Cw, -DRB1, and -DQA1 loci in a large population of North American Caucasian patients with IIM representing the major clinicopathologic groups (n = 571). We confirmed that alleles of the 8.1 ancestral haplotype were important risk markers for the development of IIM, and a random forests classification analysis suggested that within this haplotype, HLA-B*0801, DRB1*0301 and/or closely linked genes are the principal HLA risk factors. In addition, we identified several novel HLA factors associated distinctly with I or more clinicopathologic groups of IIM. The DQA1*0201 allele and associated peptide-binding Motif ((KLPLFHRL54)-K-47) were exclusive protective factors for the CD8+ T cell-mediated IIM forms of polymyositis (PM) and inclusion body myositis (IBM) (pc < 0.005). In contrast, HLA-A*68 alleles were significant risk factors for dermatomyositis (DM) (pc = 0.0021), a distinct clinical group thought to involve a humorally mediated immunopathology. While the DQA1*0301 allele was detected as a possible risk factor for IIM, PM, and DM patients (p < 0.05), DQA1*03 alleles were protective factors for IBM (pc = 0.0002). Myositis associated with malignancies was the most distinctive group of IIM wherein HLA Class I alleles were the only identifiable susceptibility factors and a shared HLA-Cw peptide-binding motif ((90)AGSHTLQWM(98)) conferred significant risk (pc = 0.019). Together, these data suggest that HLA susceptibility markers distinguish different myositis phenotypes with divergent pathogenetic mechanisms. These variations in associated HLA polymorphisms may reflect responses to unique environmental triggers resulting in the tissue pathospecificity and distinct clinicopathologic syndromes of the IIM. C1 NIEHS, Environm Autoimmun Grp, NIH, DHHS, Bethesda, MD 20892 USA. NIH, Ctr Informat Technol, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NIH, NCI, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NIAMSD, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Univ Texas, Houston Hlth Sci Ctr, Houston, TX USA. SAIC Frederick Natl Canc Inst, Basic Res Program, Frederick, MD USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. Malley Res Programming Inc, Rockville, MD USA. Mayo Clin, Rochester, MN USA. US FDA, Rockville, MD 20857 USA. RP O'Hanlon, TP (reprint author), NIEHS, Environm Autoimmun Grp, NIH, DHHS, 9 Mem Dr,Room 1W101,MSC 0958, Bethesda, MD 20892 USA. EM ohanlont@niehs.nih.gov FU NCI NIH HHS [N01-CO-12400] NR 43 TC 49 Z9 51 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0025-7974 J9 MEDICINE JI Medicine (Baltimore) PD NOV PY 2005 VL 84 IS 6 BP 338 EP 349 DI 10.1097/01.md.0000189818.63141.8c PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 985JJ UT WOS:000233373200002 PM 16267409 ER PT J AU Catellier, DJ Hannan, PJ Murray, DM Addy, CL Conway, TL Yang, S Rice, JC AF Catellier, DJ Hannan, PJ Murray, DM Addy, CL Conway, TL Yang, S Rice, JC TI Imputation of missing data when measuring physical activity by accelerometry SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Article DE EM algorithm; multiple imputation; accelerometer ID ADOLESCENT GIRLS; CHILDREN; DETERMINANTS; PROGRAM; VALUES; SCHOOL; YOUTH AB Purpose: We consider the issue of summarizing accelerometer activity count data accumulated over multiple days when the time interval in which the monitor is worn is not uniform for every subject on every day. The fact that counts are not being recorded during periods in which the monitor is not worn means that many common estimators of daily physical activity are biased downward. Methods: Data from the Trial for Activity in Adolescent Girls (TAAG), a multicenter group-randomized trial to reduce the decline in physical activity among middle-school girls, were used to illustrate the problem of bias in estimation of physical activity due to missing accelerometer data. The effectiveness of two imputation procedures to reduce bias was investigated in a simulation experiment. Count data for an entire day, or a segment of the day were deleted at random or in an informative way with higher probability of missingness at upper levels of body mass index (BMI) and lower levels of physical activity. Results: When data were deleted at random, estimates of activity computed from the observed data and those based on a data set in which the missing data have been imputed were equally unbiased; however, imputation estimates were more precise. When the data were deleted in a systematic fashion, the bias in estimated activity was lower using imputation procedures. Both imputation techniques, single imputation using the EM algorithm and multiple imputation (MI), performed similarly, with no significant differences in bias or precision. Conclusions: Researchers are encouraged to take advantage of software to implement missing value imputation, as estimates of activity are more precise and less biased in the presence of intermittent missing accelerometer data than those derived from an observed data analysis approach. C1 Univ N Carolina, Collaborat Studies Coordinating Ctr, Dept Biostat, Chapel Hill, NC 27514 USA. Univ Minnesota, Div Epidemiol, Minneapolis, MN 55455 USA. Univ Memphis, Dept Psychol, Memphis, TN 38152 USA. Univ S Carolina, Dept Epidemiol & Biostat, Columbia, SC 29208 USA. San Diego State Univ, San Diego, CA 92182 USA. NHLBI, Bethesda, MD 20892 USA. Tulane Univ, New Orleans, LA 70118 USA. RP Catellier, DJ (reprint author), Univ N Carolina, Collaborat Studies Coordinating Ctr, Dept Biostat, 137 E Franklin St, Chapel Hill, NC 27514 USA. EM diane_catellier@unc.edu FU NHLBI NIH HHS [U01HL66857, U01 HL066845, U01 HL066852, U01 HL066853, U01 HL066853-01, U01 HL066855, U01 HL066856, U01 HL066857, U01 HL066858, U01HL66845, U01HL66852, U01HL66853, U01HL66855, U01HL66856, U01HL66858] NR 21 TC 203 Z9 204 U1 2 U2 17 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD NOV PY 2005 VL 37 IS 11 SU S BP S555 EP S562 DI 10.1249/01.mss.0000185651.59486.4e PG 8 WC Sport Sciences SC Sport Sciences GA 988DS UT WOS:000233572400008 PM 16294118 ER PT J AU Masse, LC Fuemmeler, BF Anderson, CB Matthews, CE Trost, SG Catellier, DJ Treuth, M AF Masse, LC Fuemmeler, BF Anderson, CB Matthews, CE Trost, SG Catellier, DJ Treuth, M TI Accelerometer data reduction: A comparison of four reduction algorithms on select outcome variables SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Article DE actigraph; data processing; standardization ID TOTAL-ENERGY EXPENDITURE; PHYSICAL-ACTIVITY LEVELS; HEALTH ENRICHMENT MULTISITE; AFRICAN-AMERICAN GIRLS; DOUBLY-LABELED WATER; BASAL METABOLIC-RATE; SELF-REPORT; ACTIVITY MONITORS; ACTIVITY RECALL; FILIPINO YOUTH AB Purpose: Accelerometers are recognized as a valid and objective tool to assess free-living physical activity. Despite the widespread use of accelerometers, there is no standardized way to process and summarize data from them, which limits our ability to compare results across studies. This paper a) reviews decision rules researchers have used in the past, b) compares the impact of using different decision rules on a common data set, and c) identifies issues to consider for accelerometer data reduction. Methods: The methods sections of studies published in 2003 and 2004 were reviewed to determine what decision rules previous researchers have used to identify wearing period, minimal wear requirement for a valid day, spurious data, number of days used to calculate the outcome variables, and extract bouts of moderate to vigorous physical activity (MVPA). For this study, four data reduction algorithms that employ different decision rules were used to analyze the same data set. Results: The review showed that among studies that reported their decision rules, much variability was observed. Overall, the analyses suggested that using different algorithms impacted several important outcome variables. The most stringent algorithm yielded significantly lower wearing time, the lowest activity counts per minute and counts per day, and fewer minutes of MVPA per day. An exploratory sensitivity analysis revealed that the most stringent inclusion criterion had an impact on sample size and wearing time, which in turn affected many outcome variables. Conclusions: These findings suggest that the decision rules employed to process accelerometer data have a significant impact on important outcome variables. Until guidelines are developed, it will remain difficult to compare findings across studies. C1 NCI, Hlth Promot Res Branch, Behav Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Baylor Coll Med, Dept Pediat, Childrens Nutr Res Ctr, Houston, TX 77030 USA. Vanderbilt Univ, Sch Med, Div Gen Internal Med, Dept Med, Nashville, TN 37212 USA. Kansas State Univ, Dept Kinesiol, Manhattan, KS 66506 USA. Kansas State Univ, Community Hlth Inst, Manhattan, KS 66506 USA. Univ N Carolina, Dept Biostat, Chapel Hill, NC 27515 USA. Johns Hopkins Univ, Ctr Human Nutr, Baltimore, MD 21218 USA. RP Masse, LC (reprint author), NCI, Hlth Promot Res Branch, Behav Res Program, Div Canc Control & Populat Sci, Execut Plaza N,Room 4080,6130 Execut Blvd,MSC 733, Bethesda, MD 20892 USA. EM massel@mail.nih.gov RI Trost, Stewart/B-5948-2012; matthews, Charles/E-8073-2015 OI Trost, Stewart/0000-0001-9587-3944; matthews, Charles/0000-0001-8037-3103 NR 85 TC 310 Z9 311 U1 2 U2 34 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD NOV PY 2005 VL 37 IS 11 SU S BP S544 EP S554 DI 10.1249/01.mss.0000185674.09066.8a PG 11 WC Sport Sciences SC Sport Sciences GA 988DS UT WOS:000233572400007 PM 16294117 ER PT J AU Troiano, RP AF Troiano, RP TI A timely meeting: Objective measurement of physical activity SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Editorial Material C1 NCI, CDR, US Publ Hlth Serv,Risk Factors Monitoring & Metho, Appl Res Program,Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Troiano, RP (reprint author), NCI, CDR, US Publ Hlth Serv,Risk Factors Monitoring & Metho, Appl Res Program,Div Canc Control & Populat Sci, EPN 4005,6130 Execut Blvd,MSC 7344, Bethesda, MD 20892 USA. EM troianor@mail.nih.gov OI Troiano, Richard/0000-0002-6807-989X NR 1 TC 86 Z9 88 U1 0 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD NOV PY 2005 VL 37 IS 11 SU S BP S487 EP S489 DI 10.1249/01.mss.0000185473.32846.c3 PG 3 WC Sport Sciences SC Sport Sciences GA 988DS UT WOS:000233572400001 PM 16294111 ER PT J AU Ward, DS Evenson, KR Vaughn, A Rodgers, AB Troiano, RP AF Ward, DS Evenson, KR Vaughn, A Rodgers, AB Troiano, RP TI Accelerometer use in physical activity: Best practices and research recommendations SO MEDICINE AND SCIENCE IN SPORTS AND EXERCISE LA English DT Article DE accelerometry; physical activity; measurement; best practices; research AB Researchers are increasingly interested in the potential of accelerometers to improve our ability to measure and understand the health impacts of physical activity. Although accelerometers have been available commercially for more than 25 yr, broad consensus about how to use these tools has not been established. At a scientific conference in December 2004, a number of scientists were invited to present papers, serve as reactors or moderators to papers, present posters of original research, or serve as members of an audience knowledgeable about the use of accelerometers. During 2(1)/(2) d, information about best practices of accelerometer use was presented and suggestions for future research were made. From the collective experience of papers presented and discussions held, five areas of accelerometer use were described. This paper summarizes the best practices and future research needs from those five areas: monitor selection, quality, and dependability; monitor use protocols; monitor calibration; analysis of accelerometer data; and integration with other data sources. Suggestions for reporting standards for journal articles also are presented. C1 Univ N Carolina, Sch Publ Hlth, Dept Nutr, Chapel Hill, NC 27599 USA. NCI, Bethesda, MD 20892 USA. RP Ward, DS (reprint author), Univ N Carolina, Sch Publ Hlth, Dept Nutr, 4107 McGavran Greenberg,CB 7461, Chapel Hill, NC 27599 USA. EM dsward@email.unc.edu OI Troiano, Richard/0000-0002-6807-989X NR 14 TC 331 Z9 337 U1 10 U2 43 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0195-9131 J9 MED SCI SPORT EXER JI Med. Sci. Sports Exerc. PD NOV PY 2005 VL 37 IS 11 SU S BP S582 EP S588 DI 10.1249/01.mss.0000185292.71933.91 PG 7 WC Sport Sciences SC Sport Sciences GA 988DS UT WOS:000233572400011 PM 16294121 ER PT J AU Nelson, LM AF Nelson, LM TI The FMR1 premutation and premature ovarian failure SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Meeting Abstract CT 16th Annual Meeting of the North-American-Menopause-Society CY SEP 28-OCT 01, 2005 CL San Diego, CA SP N Amer Menopause Soc C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD NOV-DEC PY 2005 VL 12 IS 6 BP 781 EP 781 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 986MM UT WOS:000233453700037 ER PT J AU Yang, Q Guo, CY Cupples, LA Levy, D Wilson, PWF Fox, CS AF Yang, Q Guo, CY Cupples, LA Levy, D Wilson, PWF Fox, CS TI Genome-wide search for genes affecting serum uric acid levels: the Framingham Heart Study SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID NORTH-AMERICAN POPULATIONS; RESEARCH-CLINICS FAMILY; TRAIT LINKAGE ANALYSIS; CARDIOVASCULAR-DISEASE; QUANTITATIVE-TRAIT; ESSENTIAL-HYPERTENSION; SEGREGATION ANALYSIS; INSULIN; RISK; RESISTANCE AB Serum uric acid levels are associated with hypertension, cardiovascular disease, and renal disease. Uric acid has been shown to be heritable; however, genome-wide linkage analyses have not been reported. Genome-wide multipoint variance components linkage analyses with 401 markers spaced at approximately 10 centimorgan (cM) were conducted on 1258 subjects of the Framingham Heart Study, using the average of two serum uric acid measurements obtained in examinations I and 2 around 1971 and 1979. Covariates in fully adjusted model included sex, age, body mass index (BMI), serum creatinine, alcohol consumption, diabetes, diuretic treatment, and triglycerides. To investigate possible pleiotropic effects between uric acid and covariates that may have a genetic component, bivariate linkage analyses of uric acid with BMI, triglycerides, and glucose were conducted at the uric acid linkage regions. The heritability of uric acid was 0.63. The highest multipoint log-of-the-odds (LOD) score was 3.3 at 50 cM on chromosome 15 for age-sex-adjusted uric acid, but decreased to 1.5 after multivariable adjustment. Additional evidence of linkage was seen on chromosomes 2 (LOD score 1.1 at 4 cM) and 8 (LOD score 1.7 at 6 cM) for multivariable-adjusted uric acid. Pleiotropic effects were only found between uric acid and glucose and BMI at chromosomes 8 and 15 linkage locations, respectively. We have identified several novel loci linked to uric acid. We found possible pleiotropic effects between uric acid and BNI and glucose. Further research is necessary to identify the genes involved in uric acid metabolism and their roles in hypertension, cardiovascular disease, and renal disease. (c) 2005 Elsevier Inc. All rights reserved. C1 Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. Natl Hearat Lung & Blood Inst Framingham Heart St, Framingham, MA 01702 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. Natl Heart Lung & Blood Inst, NIH, Bethesda, MD 20892 USA. RP Yang, Q (reprint author), Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. EM qyang@bu.edu RI Yang, Qiong/G-5438-2014; OI Yang, Qiong/0000-0002-3658-1375; Cupples, L. Adrienne/0000-0003-0273-7965 FU NHLBI NIH HHS [N01-HC-25195] NR 36 TC 56 Z9 65 U1 1 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD NOV PY 2005 VL 54 IS 11 BP 1435 EP 1441 DI 10.1016/j.metabol.2005.05.007 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 984HP UT WOS:000233294000004 PM 16253630 ER PT J AU Reimers, M Heilig, M Sommer, WH AF Reimers, M Heilig, M Sommer, WH TI Gene discovery in neuropharmacological and behavioral studies using Affymetrix microarray data SO METHODS LA English DT Article DE brain; expression microarray; regional hybridization bias; statistical analysis ID PROBE LEVEL DATA; MESSENGER-RNA; EXPRESSION; BRAIN; FOS; ALCOHOLISM; SUMMARIES; MODEL AB We describe methods and software tools for doing data analysis based on Affymetrix microarray data, emphasizing often neglected issues. In our experience with neuroscience studies, experimental design and quality assessment are vital. We also describe in detail the pre-processing methods we have found useful for Affymetrix data. Finally, we summarize the statistical literature and describe some pitfalls in the post-processing analysis. (c) 2005 Elsevier Inc. All rights reserved. C1 NIH, NCI, Mol Pharmacol Lab, Bethesda, MD 20892 USA. NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD USA. RP Reimers, M (reprint author), NIH, NCI, Mol Pharmacol Lab, Bethesda, MD 20892 USA. EM reimersm@mail.nih.gov OI Heilig, Markus/0000-0003-2706-2482; Sommer, Wolfgang/0000-0002-5903-6521 NR 26 TC 14 Z9 14 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 1046-2023 J9 METHODS JI Methods PD NOV PY 2005 VL 37 IS 3 BP 219 EP 228 DI 10.1016/j.ymeth.2005.09.002 PG 10 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 993VF UT WOS:000233982800002 PM 16308151 ER PT J AU Golebiowski, F Kasprzak, KS AF Golebiowski, F Kasprzak, KS TI Inhibition of core histones acetylation by carcinogenic nickel(II) SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article; Proceedings Paper CT 3rd International Conference on Molecular Mechanisms of Metal Toxicity and Carcinogenesis CY SEP 11-15, 2004 CL Morgantown, VA SP Natl Inst Occupat Safety & Hlth, Elementis Chromium, Corpus, Nickel Producers Environm Res Assoc, Nutr 21 Inc Purchase ID GENE-EXPRESSION; EPITHELIAL-CELLS; OXIDATIVE DAMAGE; H4 ACETYLATION; METHYLATION; EXPOSURE; H3 AB Nickel, a well-established human carcinogen, was shown to decrease acetylation of histones H4 and H3 in cultured cells. Such a decrease is expected to suppress gene expression. However, nickel is known to not only suppress but also enhance the expression of many genes. So, perhaps, nickel can alter histone acetylation in a more complex way? In a first step of testing this presumption, we examined acetylation status of histones H2A, H2B, H3 and H4, in human (HAE) and rat (NRK) cells exposed to nickel(II) under various conditions. In both cell lines, acetylation of all four histones was down-regulated by nickel(II) in a concentration- and time-dependent manner. Acetylation of histone H2B was suppressed to greater extent than that of the others, with histone H3 being relatively least affected. The analysis of acetylation status of each of the four lysine sites at the N-terminal tail of histone H2B revealed decreases consistent with those observed in the total acetylation patterns, with the K12 and K20 residues being markedly more affected than K5 and K15 residues. Thus, the decrease in acetylation was to some degree site specific. In NRK cells, the observed uniform down-regulation of histone acetylation was consistent with a marked suppression of global gene transcription measured as [H-3]-uridine incorporation into mRNA. However, in HAE cells, global RNA expression was transiently increased (in 24 h) before dropping below control after longer exposure (3 days). In conclusion, the effects of Ni(II) on histone acetylation are inhibitory, with their extent depending on the dose and exposure time. This uniform inhibition, however, is not consistently reflected in global RNA expression that in HAE cells may include both increase and decrease of the expression, clearly indicating the involvement of factors other than histone acetylation. The observed effects may contribute to neoplastic transformation of Ni(II)-exposed cells. C1 NCI, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. RP Golebiowski, F (reprint author), NCI, Comparat Carcinogenesis Lab, Bldg 538,Room 205E, Frederick, MD 21702 USA. EM filip@ncifcrf.gov NR 20 TC 44 Z9 67 U1 0 U2 4 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0300-8177 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD NOV PY 2005 VL 279 IS 1-2 BP 133 EP 139 DI 10.1007/s11010-005-8285-1 PG 7 WC Cell Biology SC Cell Biology GA 983ME UT WOS:000233235500014 PM 16283522 ER PT J AU Mitsunari, T Nakatsu, F Shioda, N Love, PE Grinberg, A Bonifacino, JS Ohno, H AF Mitsunari, T Nakatsu, F Shioda, N Love, PE Grinberg, A Bonifacino, JS Ohno, H TI Clathrin adaptor AP-2 is essential for early embryonal development SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID LYSOSOMAL MEMBRANE-PROTEINS; POLARIZED EPITHELIAL-CELLS; MEDIATED ENDOCYTOSIS; CAENORHABDITIS-ELEGANS; SORTING SIGNALS; ALPHA-ADAPTIN; SYNAPTIC VESICLES; BINDING-SITE; RECEPTOR; COMPLEX AB The heterotetrameric adaptor protein (AP) complexes AP-1, AP-2, AP-3, and AP-4 play key roles in transport vesicle formation and cargo sorting in post-Golgi trafficking pathways. Studies on cultured mammalian cells have shown that AP-2 mediates rapid endocytosis of a subset of plasma membrane receptors. To determine whether this function is essential in the context of a whole mammalian organism, we carried out targeted disruption of the gene encoding the mu 2 subunit of AP-2 in the mouse. We found that mu 2 heterozygous mutant mice were viable and had an apparently normal phenotype. In contrast, no mu 2 homozygous mutant embryos were identified among blastocysts from intercrossed heterozygotes, indicating that mu 2-deficient embryos die before day 3.5 postcoitus (E3.5). These results indicate that AP-2 is indispensable for early embryonic development, which might be due to its requirement for cell viability. C1 RIKEN, Lab Epithelial Immunobiol, Res Ctr Allergy & Immunol, Yokohama, Kanagawa 2300045, Japan. Kanazawa Univ, Inst Canc Res, Kanazawa, Ishikawa 9200934, Japan. NICHHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. Yokohama City Univ, Int Grad Sch Arts & Sci, Yokohama, Kanagawa 2300045, Japan. RP Ohno, H (reprint author), RIKEN, Lab Epithelial Immunobiol, Res Ctr Allergy & Immunol, 1-7-22 Suehiro, Yokohama, Kanagawa 2300045, Japan. EM ohno@rcai.riken.jp RI Ohno, Hiroshi/L-7899-2014; OI Ohno, Hiroshi/0000-0001-8776-9661; Bonifacino, Juan S./0000-0002-5673-6370 NR 48 TC 63 Z9 66 U1 1 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD NOV PY 2005 VL 25 IS 21 BP 9318 EP 9323 DI 10.1128/MCB.25.21.9318-9323.2005 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 976SW UT WOS:000232754600014 PM 16227583 ER PT J AU Takahashi, Y Karbowski, M Yamaguchi, H Kazi, A Wu, J Sebti, SM Youle, RJ Wang, HG AF Takahashi, Y Karbowski, M Yamaguchi, H Kazi, A Wu, J Sebti, SM Youle, RJ Wang, HG TI Loss of Bif-1 suppresses Bax/Bak conformational change and mitochondrial apoptosis SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID CYTOCHROME-C RELEASE; BCL-2 FAMILY-MEMBERS; ENDOPLASMIC-RETICULUM; MEMBRANE PERMEABILIZATION; CELL-DEATH; PROAPOPTOTIC BAX; OLIGOMERIZES BAK; ENDOPHILIN A1; BH3 DOMAINS; PROTEIN AB Bif-1, a member of the endophilin B protein family, interacts with Bax and promotes interleukin-3 withdrawal-induced Bax conformational change and apoptosis when overexpressed in FL5.12 cells. Here, we provide evidence that Bif-1 plays a regulatory role in apoptotic activation of not only Bax but also Bak and appears to be involved in suppression of tumorigenesis. Inhibition of endogenous Bif-1 expression in HeLa cells by RNA interference abrogated the conformational change of Bax and Bak, cytochrome c release, and caspase 3 activation induced by various intrinsic death signals. Similar results were obtained in Bif-1 knockout mouse embryonic fibroblasts. While Bif-1 did not directly interact with Bak, it heterodimerized with Bax on mitochondria in intact cells, and this interaction was enhanced by apoptosis induction and preceded the Bax conformational change. Moreover, suppression of Bif-1 expression was associated with an enhanced ability of HeLa cells to form colonies in soft agar and tumors in nude mice. Taken together, these findings support the notion that Bif-1 is an important component of the mitochondrial pathway for apoptosis as a novel Bax/Bak activator, and loss of this proapoptotic molecule may contribute to tumorigenesis. C1 Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Drug Discovery Program, Tampa, FL 33612 USA. Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Mol Oncol Program, Tampa, FL 33612 USA. Univ S Florida, Coll Med, Res Inst, Dept Interdisciplinary Oncol, Tampa, FL 33612 USA. NINDS, Biochem Sect, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Wang, HG (reprint author), Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Drug Discovery Program, 12902 Magnolia Dr, Tampa, FL 33612 USA. EM wanghg@moffitt.usf.edu RI Wang, Hong-Gang/A-3018-2015 FU NCI NIH HHS [CA 82197, R01 CA082197] NR 65 TC 119 Z9 120 U1 0 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD NOV PY 2005 VL 25 IS 21 BP 9369 EP 9382 DI 10.1128/MCB.25.21.9369-9382.2005 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 976SW UT WOS:000232754600019 PM 16227588 ER PT J AU de Silanes, IL Galban, S Martindale, JL Yang, XL Mazan-Mamczarz, K Indig, FE Falco, G Zhan, M Gorospe, M AF de Silanes, IL Galban, S Martindale, JL Yang, XL Mazan-Mamczarz, K Indig, FE Falco, G Zhan, M Gorospe, M TI Identification and functional outcome of mRNAs associated with RNA-binding protein TIA-1 SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID AU-RICH ELEMENT; MAMMALIAN STRESS GRANULES; GENE-EXPRESSION; POSTTRANSCRIPTIONAL REGULATION; TRANSLATIONAL SILENCER; HUR; STABILITY; REGULATOR; ALPHA; CYCLOOXYGENASE-2 AB The RNA-binding protein TIA-1 (T-cell intracellular antigen 1) functions as a posttranscriptional regulator of gene expression and aggregates to form stress granules following cellular damage. TIA-1 was previously shown to bind mRNAs encoding tumor necrosis factor alpha (TNF-alpha) and cyclooxygenase 2 (COX-2), but TIA-1 target mRNAs have not been systematically identified. Here, immunoprecipitation (IP) of TIA-1-RNA complexes, followed by microarray-based identification and computational analysis of bound transcripts, was used to elucidate a common motif present among TIA-1 target mRNAs. The predicted TIA-1 motif was a U-rich, 30- to 37-nucleotide (nt)-long bipartite element forming loops of variable size and a bent stem. The TIA-1 motif was found in the TNF-alpha and COX-2 mRNAs and in 3,019 additional UniGene transcripts (similar to 3% of the UniGene database), localizing preferentially to the 3' untranslated region. The interactions between TIA-1 and target transcripts were validated by IP of endogenous mRNAs, followed by reverse transcription and PCR-mediated detection, and by pulldown of biotinylated RNAs, followed by Western blotting. Further studies using RNA interference revealed that TIA-1 repressed the translation of bound mRNAs. In summary, we report a signature motif present in mRNAs that associate with TIA-1 and provide support to the notion that TIA-1 represses the translation of target transcripts. C1 NIA, IRP, LCMB, NIH, Baltimore, MD 21224 USA. NIA, IRP, Res Resources Branch, NIH, Baltimore, MD 21224 USA. NIA, IRP, Genet Lab, NIH, Baltimore, MD 21224 USA. RP Gorospe, M (reprint author), NIA, IRP, LCMB, NIH, Box 12,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM zhanmi@mail.nih.gov; myriam-gorospe@nih.gov RI Lopez de Silanes, Isabel/K-4962-2015 OI Lopez de Silanes, Isabel/0000-0001-6762-9792 NR 43 TC 114 Z9 116 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD NOV PY 2005 VL 25 IS 21 BP 9520 EP 9531 DI 10.1128/MCB.25.21.9520-9531.2005 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 976SW UT WOS:000232754600033 ER PT J AU Wu, Z Kim, HP Xue, HH Liu, H Zhao, KJ Leonard, WJ AF Wu, Z Kim, HP Xue, HH Liu, H Zhao, KJ Leonard, WJ TI Interleukin-21 receptor gene induction in human T cells is mediated by T-cell receptor-induced Sp1 activity SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TRANSCRIPTION FACTOR SP1; DNA-BINDING ACTIVITY; COMMON GAMMA-CHAIN; NF-KAPPA-B; IL-21 RECEPTOR; PROTEIN-KINASE; GROWTH-FACTOR; BETA-CHAIN; ADAPTIVE IMMUNITY; PROMOTER ACTIVITY AB Interleukin-21 (IL-21) plays important roles in regulating the immune response. IL-21 receptor (IL-21R) mRNA is expressed at a low level in human resting T cells but is rapidly induced by mitogenic stimulation. We now investigate the basis for IL21R gene regulation in T cells. We found that the -80 to -20 region critically regulates IL-21R promoter activity and corresponds to a major DNase I-hypersensitive site. Electrophoretic mobility shift assays, DNA affinity chromatography followed by mass spectrometry, and chromatin immunoprecipitation assays revealed that Sp1 binds to this region in vitro and in vivo. Moreover, mutation of the Sp1 motif markedly reduced IL-21R promoter activity, and Sp1 small interfering RNAs effectively diminished IL-21R expression in activated T cells. Interestingly, upon T-cell receptor (TCR) stimulation, T cells increased IL-21R expression and Sp1 protein levels while decreasing Sp1 phosphorylation. Moreover, phosphatase inhibitors that increased phosphorylation of Sp1. diminished IL-21R transcription. These data indicate that TCR-induced IL-21R expression is driven by TCR-mediated augmentation of Sp1 protein levels and may partly depend on the dephosphorylation of Sp1. C1 NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. RP Leonard, WJ (reprint author), NHLBI, Lab Mol Immunol, NIH, Bldg 10,Room 7N252, Bethesda, MD 20892 USA. EM wjl@helix.nih.gov FU Intramural NIH HHS NR 58 TC 30 Z9 32 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD NOV PY 2005 VL 25 IS 22 BP 9741 EP 9752 DI 10.1128/MCB.25.22.9741-9752.2005 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 980VQ UT WOS:000233046700001 PM 16260592 ER PT J AU Dong, JS Lai, R Jennings, JL Link, AJ Hinnebusch, AG AF Dong, JS Lai, R Jennings, JL Link, AJ Hinnebusch, AG TI The novel ATP-binding cassette protein ARB1 is a shuttling factor that stimulates 40S and 60S ribosome biogenesis SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TRANSLATION INITIATION-FACTOR; SACCHAROMYCES-CEREVISIAE; NUCLEAR EXPORT; PRE-RIBOSOMES; KINASE GCN2; MASS-SPECTROMETRY; SUBUNIT BIOGENESIS; IN-VITRO; YEAST; RNA AB ARB1 is an essential yeast protein closely related to members of a subclass of the ATP-binding cassette (ABC) superfamily of proteins that are known to interact with ribosomes and function in protein synthesis or ribosome biogenesis. We show that depletion of ARB1 from Saccharomyces cerevisiae cells leads to a deficit in 18S rRNA and 40S subunits that can be attributed to slower cleavage at the A0, A1, and A2 processing sites in 35S pre-rRNA, delayed processing of 20S rRNA to mature 18S rRNA, and a possible defect in nuclear export of pre-40S subunits. Depletion of ARB1 also delays rRNA processing events in the 60S biogenesis pathway. We further demonstrate that ARB1 shuttles from nucleus to cytoplasm, cosediments with 40S, 60S, and 80S/90S ribosomal species, and is physically associated in vivo with TIF6, LSG1, and other proteins implicated previously in different aspects of 60S or 40S biogenesis. Mutations of conserved ARB1 residues expected to function in ATP hydrolysis were lethal. We propose that ARB1 functions as a mechanochemical ATPase to stimulate multiple steps in the 40S and 60S ribosomal biogenesis pathways. C1 NICHHD, Lab Gene Regulat & Dev, Bethesda, MD 20892 USA. Vanderbilt Univ, Dept Microbiol & Immunol, Sch Med, Nashville, TN 37232 USA. RP Hinnebusch, AG (reprint author), NIH, Bldg 6A,Room B1A13, Bethesda, MD 20892 USA. EM ahinnebusch@nih.gov FU NCI NIH HHS [P50 CA098131, CA098131]; NHLBI NIH HHS [HL68744, P01 HL068744]; NIEHS NIH HHS [R01 ES011993, ES11993]; NIGMS NIH HHS [R01 GM064779, GM64779] NR 78 TC 23 Z9 26 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD NOV PY 2005 VL 25 IS 22 BP 9859 EP 9873 DI 10.1128/MCB.25.22.9859-9873.2005 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 980VQ UT WOS:000233046700011 PM 16260602 ER PT J AU Ward, IM Difilippantonio, S Minn, K Mueller, MD Molina, JR Yu, XC Frisk, CS Ried, T Nussenzweig, A Chen, JJ AF Ward, IM Difilippantonio, S Minn, K Mueller, MD Molina, JR Yu, XC Frisk, CS Ried, T Nussenzweig, A Chen, JJ TI 53BP1 cooperates with p53 and functions as a haploinsufficient tumor suppressor in mice SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID DOUBLE-STRAND BREAKS; DNA-DAMAGE-RESPONSE; CLASS-SWITCH RECOMBINATION; HISTONE H2AX; PROTEIN 53BP1; V(D)J RECOMBINATION; GENE AMPLIFICATION; CHECKPOINT GENES; THYMIC LYMPHOMA; IN-VIVO AB p53 binding protein 1 (53BP1) is a putative DNA damage sensor that accumulates at sites of double-strand breaks (DSBs) in a manner dependent on histone H2AX. Here we show that the loss of one or both copies of 53BP1 greatly accelerates lymphomagenesis in a p53-null background, suggesting that 53BP1 and p53 cooperate in tumor suppression. A subset of 53BP1(-/-) p53(-/-) lymphomas, like those in H2AX(-/-) p53(-/-) mice, were diploid and harbored clonal translocations involving antigen receptor loci, indicating misrepair of DSBs during V(D)J recombination as one cause of oncogenic transformation. Loss of a single 53BP1 allele compromised genomic stability and DSB repair, which could explain the susceptibility of 53BP1(+/-) mice to tumorigenesis. In addition to structural aberrations, there were high rates of chromosomal missegregation and accumulation of aneuploid cells in 53BP1(-/-) p53(+/+) and 53BP1(-/-) p53(-/-) tumors as well as in primary 53BP1(-/-) splenocytes. We conclude that 53BP1 functions as a dosage-dependent caretaker that promotes genomic stability by a mechanism that preserves chromosome structure and number. C1 Mayo Clin & Mayo Fdn, Div Oncol Res, Rochester, MN 55905 USA. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. Mayo Clin & Mayo Fdn, Dept Med Oncol, Rochester, MN 55905 USA. Mayo Clin & Mayo Fdn, Dept Comparat Med, Rochester, MN 55905 USA. NCI, Genet Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Chen, JJ (reprint author), Mayo Clin & Mayo Fdn, Div Oncol Res, Guggenheim 1342, Rochester, MN 55905 USA. EM junjie.chen@mayo.edu FU NCI NIH HHS [CA100109, R01 CA100109] NR 37 TC 58 Z9 61 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD NOV PY 2005 VL 25 IS 22 BP 10079 EP 10086 DI 10.1128/MCB.25.22.10079-10086.2005 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 980VQ UT WOS:000233046700030 PM 16260621 ER PT J AU Ellis, CE Murphy, EJ Mitchell, DC Golovko, MY Scaglia, F Barcelo-Coblijn, GC Nussbaum, RL AF Ellis, CE Murphy, EJ Mitchell, DC Golovko, MY Scaglia, F Barcelo-Coblijn, GC Nussbaum, RL TI Mitochondrial lipid abnormality and electron transport chain impairment in mice lacking alpha-synuclein SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID NADH-UBIQUINONE OXIDOREDUCTASE; CYTOCHROME-C OXIDOREDUCTASE; FATTY-ACID INCORPORATION; GENE-ABLATED MICE; PARKINSONS-DISEASE; NONSYNAPTIC MITOCHONDRIA; BRAIN MITOCHONDRIA; RESPIRATORY-CHAIN; BINDING PROTEINS; BETA-SYNUCLEINS AB The presynaptic protein alpha-synuclein, implicated in Parkinson disease (PD), binds phospholipids and has a role in brain fatty acid (FA) metabolism. In mice lacking alpha-synuclein (Snca(-/-)), total brain steady-state mass of the mitochondria-specific phospholipid, cardiolipin, is reduced 22% and its acyl side chains show a 51% increase in saturated FAs and a 25% reduction in essential n-6, but not n-3, polyunsaturated FAs. Additionally, 23% reduction in phosphatidylglycerol content, the immediate biosynthetic precursor of cardiolipin, was observed without alterations in the content of other brain phospholipids. Consistent with these changes, more ordered lipid head group and acyl chain packing with enhanced rotational motion of diphenylhexatriene (DPH) about its long axis were demonstrated in time-resolved DPH fluorescence lifetime experiments. These abnormalities in mitochondrial membrane properties were associated with a 15% reduction in linked complex I/III activity of the electron transport chain, without reductions in mitochondrial number, complex II/III activity, or individual complex I, II, III, or IV activity. Reduced complex I activity is thought to be a critical factor in the development of PD. Thus, altered membrane composition and structure and impaired complex I/III function in Snca(-/-) brain suggest a relationship between et-synuclein's role in brain lipid metabolism, mitochondrial function, and PD. C1 NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. Univ N Dakota, Dept Pharmacol Physiol & Therapeut, Sch Med & Hlth Sci, Grand Forks, ND 58202 USA. NIAAA, Lab Membrane Biophys & Biochem, NIH, Bethesda, MD 20892 USA. Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. RP Nussbaum, RL (reprint author), NHGRI, Genet Dis Res Branch, NIH, 49 Convent Dr,MSC 4472, Bethesda, MD 20892 USA. EM rlnuss@nhgri.nih.gov FU Intramural NIH HHS; NHGRI NIH HHS [Z01 HG000117-09]; NINDS NIH HHS [1R21 NS043697-01A, R21 NS043697]; PHS HHS [5P20R01-7699-02] NR 78 TC 119 Z9 124 U1 0 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD NOV PY 2005 VL 25 IS 22 BP 10190 EP 10201 DI 10.1128/MCB.25.22.10190-10201.2005 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 980VQ UT WOS:000233046700040 PM 16260631 ER PT J AU Theos, AC Tenza, D Martina, JA Hurbain, I Peden, AA Sviderskaya, EV Stewart, A Robinson, MS Bennett, DC Cutler, DF Bonifacino, JS Marks, MS Raposo, GA AF Theos, AC Tenza, D Martina, JA Hurbain, I Peden, AA Sviderskaya, EV Stewart, A Robinson, MS Bennett, DC Cutler, DF Bonifacino, JS Marks, MS Raposo, GA TI Functions of adaptor protein (AP)-3 and AP-1 in tyrosinase sorting from endosomes to melanosomes SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID HERMANSKY-PUDLAK-SYNDROME; MANNOSE 6-PHOSPHATE RECEPTORS; IMMATURE SECRETORY GRANULES; LYSOSOMAL MEMBRANE-PROTEINS; CLATHRIN-COATED VESICLES; DI-LEUCINE; MOUSE MELANOCYTES; BETA-3A SUBUNIT; LOCUS PROTEIN; PC12 CELLS AB Specialized cells exploit adaptor protein complexes for unique post-Golgi sorting events, providing a unique model system to specify adaptor function. Here, we show that AP-3 and AP-1 function independently in sorting of the melanocyte-specific protein tyrosinase from endosomes to the melanosome, a specialized lysosome-related organelle distinguishable from lysosomes. AP-3 and AP-1 localize in melanocytes primarily to clathrin-coated buds on tubular early endosomes near melanosomes. Both adaptors recognize the tyrosinase dileucine-based melanosome sorting signal, and tyrosinase largely colocalizes with each adaptor on endosomes. In AP-3-deficient melanocytes, tyrosinase accumulates inappropriately in vacuolar and multivesicular endosomes. Nevertheless, a substantial fraction still accumulates on melanosomes, concomitant with increased association with endosomal AP-1. Our data indicate that AP-3 and AP-1 function in partially redundant pathways to transfer tyrosinase from distinct endosomal subdomains to melanosomes and that the AP-3 pathway ensures that tyrosinase averts entrapment on internal membranes of forming multivesicular bodies. C1 Inst Curie, CNRS, Unite Mixte Rech 144, F-75248 Paris, France. Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. Univ Cambridge, Cambridge Inst Med Res, Wellcome Trust, Cambridge CB2 2XY, England. NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. Genentech Inc, San Francisco, CA 94080 USA. Univ London St Georges Hosp, Sch Med, Dept Basic Med Sci, London SW17 ORE, England. UCL, MRC, Mol Cell Biol Lab, Cell Biol Unit, London WC1E BT, England. UCL, Dept Biochem & Mol Biol, London WC1E BT, England. RP Raposo, GA (reprint author), Inst Curie, CNRS, Unite Mixte Rech 144, F-75248 Paris, France. EM g.raposo@curie.fr RI Bennett, Dorothy/C-2418-2008; Sviderskaya, Elena/D-2419-2009; OI Bennett, Dorothy/0000-0002-3639-7527; Marks, Michael/0000-0001-7435-7262; Bonifacino, Juan S./0000-0002-5673-6370 FU NCI NIH HHS [T32 CA 09140, T32 CA009140]; NEI NIH HHS [EY015625, R01 EY015625]; NIAMS NIH HHS [AR048155, R01 AR048155]; Wellcome Trust NR 67 TC 134 Z9 140 U1 1 U2 4 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2005 VL 16 IS 11 BP 5356 EP 5372 DI 10.1091/mbc.E05-07-0626 PG 17 WC Cell Biology SC Cell Biology GA 980NK UT WOS:000233025000028 PM 16162817 ER PT J AU Gillette, WK Esposito, D Frank, PH Zhou, M Yu, LR Jozwik, C Zhang, XY McGowan, B Jacobowitz, DM Pollard, HB Hao, T Hill, DE Vidal, M Conrads, TP Veenstra, TD Hartley, JL AF Gillette, WK Esposito, D Frank, PH Zhou, M Yu, LR Jozwik, C Zhang, XY McGowan, B Jacobowitz, DM Pollard, HB Hao, T Hill, DE Vidal, M Conrads, TP Veenstra, TD Hartley, JL TI Pooled ORF expression technology (POET) - Using proteomics to screen pools of open reading frames for protein expression SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Article ID IMMOBILIZED PH GRADIENTS; ORFEOME VERSION 1.1; FUNCTIONAL GENOMICS; C-ELEGANS; ELECTROPHORESIS; CLONING; STATE; TAGS; DNA AB We have developed a pooled ORF expression technology, POET, that uses recombinational cloning and proteomic methods (two-dimensional gel electrophoresis and mass spectrometry) to identify ORFs that when expressed are likely to yield high levels of soluble, purified protein. Because the method works on pools of ORFs, the procedures needed to subclone, express, purify, and assay protein expression for hundreds of clones are greatly simplified. Small scale expression and purification of 12 positive clones identified by POET from a pool of 688 Caenorhabditis elegans ORFs expressed in Escherichia coli yielded on average 6 times as much protein as 12 negative clones. Larger scale expression and purification of six of the positive clones yielded 47-374 mg of purified protein/liter. Using POET, pools of ORFs can be constructed, and the pools of the resulting proteins can be analyzed and manipulated to rapidly acquire information about the attributes of hundreds of proteins simultaneously. C1 NCI, Prot Express Lab, NIH, SAIC Frederick Inc,Res Technol Program, Frederick, MD 21702 USA. NCI, Lab Proteom & Anal Technol, NIH, SAIC Frederick Inc,Res Technol Program, Frederick, MD 21702 USA. Uniformed Serv Univ Hlth Sci, Dept Anat Physiol & Genet, Bethesda, MD 20814 USA. Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. NIMH, Clin Sci Lab, Bethesda, MD 20892 USA. RP Hartley, JL (reprint author), NCI, Prot Express Lab, NIH, SAIC Frederick Inc,Res Technol Program, POB B, Frederick, MD 21702 USA. EM hartley@ncifcrf.gov RI Hill, David/B-6617-2011 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 21 TC 11 Z9 12 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD NOV PY 2005 VL 4 IS 11 BP 1647 EP 1652 DI 10.1074/mcp.M500128-MCP200 PG 6 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 981ZF UT WOS:000233125800001 PM 16113400 ER PT J AU Hood, BL Darfler, MM Guiel, TG Furusato, B Lucas, DA Ringeisen, BR Sesterhenn, IA Conrads, TP Veenstra, TD Krizman, DB AF Hood, BL Darfler, MM Guiel, TG Furusato, B Lucas, DA Ringeisen, BR Sesterhenn, IA Conrads, TP Veenstra, TD Krizman, DB TI Proteomic analysis of formalin-fixed prostate cancer tissue SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Article ID LASER-CAPTURE MICRODISSECTION; MACROPHAGE-INHIBITORY CYTOKINE-1; TANDEM MASS-SPECTROMETRY; GENE-EXPRESSION PATTERNS; ACID-PHOSPHATASE; EMBEDDED TISSUE; PROTEIN; CARCINOMA; GROWTH; O-18 AB Proteomic analysis of formalin-fixed paraffin-embedded (FFPE) tissue would enable retrospective biomarker investigations of this vast archive of pathologically characterized clinical samples that exist worldwide. These FFPE tissues are, however, refractory to proteomic investigations utilizing many state of the art methodologies largely due to the high level of covalently cross-linked proteins arising from formalin fixation. A novel tissue microdissection technique has been developed and combined with a method to extract soluble peptides directly from FFPE tissue for mass spectral analysis of prostate cancer (PCa) and benign prostate hyperplasia (BPH). Hundreds of proteins from PCa and BPH tissue were identified, including several known PCa markers such as prostate-specific antigen, prostatic acid phosphatase, and macrophage inhibitory cytokine-1. Quantitative proteomic profiling utilizing stable isotope labeling confirmed similar expression levels of prostate-specific antigen and prostatic acid phosphatase in BPH and PCa cells, whereas the expression of macrophage inhibitory cytokine-1 was found to be greater in PCa as compared with BPH cells. C1 Express Pathol Inc, Gaithersburg, MD 20877 USA. NCI, Lab Proteom & Anal Technol, SAIC Frederick Inc, Frederick, MD 21702 USA. Armed Forces Inst Pathol, Dept Genitourinary Pathol, Washington, DC 20306 USA. USN, Res Lab, Washington, DC 20375 USA. RP Veenstra, TD (reprint author), Express Pathol Inc, 9290 Gaither Rd, Gaithersburg, MD 20877 USA. EM veenstra@ncifcrf.gov; d.krizman@expressionpathology.com OI Furusato, Bungo/0000-0003-4614-9882 FU NCI NIH HHS [N01-CO-12400] NR 40 TC 179 Z9 185 U1 0 U2 17 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD NOV PY 2005 VL 4 IS 11 BP 1741 EP 1753 DI 10.1074/mcp.M500102-MCP200 PG 13 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 981ZF UT WOS:000233125800010 PM 16091476 ER PT J AU Shima, Y Zubair, M Ishihara, S Shinohara, Y Oka, S Kimura, S Okamoto, S Minokoshi, Y Suita, S Morohashi, KI AF Shima, Y Zubair, M Ishihara, S Shinohara, Y Oka, S Kimura, S Okamoto, S Minokoshi, Y Suita, S Morohashi, KI TI Ventromedial hypothalamic nucleus-specific enhancer of Ad4BP/SF-1 gene SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID RECEPTOR STEROIDOGENIC FACTOR-1; PROTEIN LINEAGE MARKER; ENDOCRINE DEVELOPMENT; TRANSCRIPTION FACTOR; BASAL TELENCEPHALON; NEURAL PLATE; FACTOR-I; MOUSE; EXPRESSION; NEURONS AB Ad4BP/SF-1 [Ad4 binding protein/steroidogenic factor-1 (designated NR5A1)] is a transcription factor essential for animal reproduction. Based on the phenotypes observed in gene-disrupted mice, Ad4BP/SF-1 is thought to be involved in establishment of the hypothalamic-pituitary-gonadal axis. However, the mechanisms underlying tissue-specific expression of Ad4BP/SF-1 are largely unknown. Here, we investigated the cis-regulatory regions of the mouse Ad4BP/SF-1 gene by transgenic mouse assays, and identified a ventromedial hypothalamic nucleus (VMH)-specific enhancer. The enhancer localized in intron 6 is highly conserved between mouse, human, and chick. The enhancer has the potential to reproduce endogenous gene expression from the fetal ventromedial diencephalon to the adult VMH. The VMH enhancer was characterized by the presence of suppressive and activating elements. Mutation of the former element resulted in ectopic lacZ reporter gene expression in an area dorsal to the intrinsic expression domain and in the ventricular zone, whereas mutations in the latter containing ATTA motifs led to the disappearance of the reporter gene expression, suggesting the involvement of homeobox proteins. Using nuclear extracts prepared from the adult hypothalami, EMSAs identified specific protein binding to the activating elements but not to the suppressive element. C1 Natl Inst Nat Sci, Div Sex Differentiat, Natl Inst Basic Biol, Okazaki, Aichi 4448787, Japan. Japan Sci & Technol Corp, CREST, Kawaguchi 3320012, Japan. Kyushu Univ, Dept Pediat Surg, Grad Sch Med Sci, Higashi Ku, Fukuoka 8128582, Japan. NIH, Lab Metab, Bethesda, MD 20892 USA. Natl Inst Nat Sci, Div Endocrinol & Metab, Dept Dev Physiol, Natl Inst Physiol Sci, Okazaki, Aichi 4448585, Japan. RP Morohashi, KI (reprint author), Natl Inst Nat Sci, Div Sex Differentiat, Natl Inst Basic Biol, Okazaki, Aichi 4448787, Japan. EM moro@nibb.ac.jp NR 49 TC 27 Z9 30 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD NOV PY 2005 VL 19 IS 11 BP 2812 EP 2823 DI 10.1210/me.2004-0431 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 977MQ UT WOS:000232808300013 PM 15994202 ER PT J AU Fowler, JS Logan, J Volkow, ND Wang, GJ AF Fowler, JS Logan, J Volkow, ND Wang, GJ TI Translational neuroimaging: Positron emission tomography studies of monoamine oxidase SO MOLECULAR IMAGING AND BIOLOGY LA English DT Review DE monoamine oxidase; brain; tobacco smoke; PET ID HEALTHY-HUMAN SUBJECTS; PERIPHERAL ORGANS; HUMAN-BRAIN; PARKINSONS-DISEASE; CIGARETTE-SMOKING; L-DEPRENYL; MAO-B; AGGRESSIVE-BEHAVIOR; POINT MUTATION; SMOKERS AB Positron emission tomography (PET) using radiotracers with high molecular specificity is an important scientific tool in studies of monoamine oxidase (MAO), an important enzyme in the regulation of the neurotransmitters dopamine, norepinephrine, and serotonin as well as the dietary amine, tyramine. MAO occurs in two different subtypes, MAO A and MAO B, which have different substrate and inhibitor specificity and which are different gene products. The highly variable subtype distribution with different species makes human studies of special value. MAO A and B can be imaged in the human brain and certain peripheral organs using PET and carbon-11 (half-life 20.4 minutes) labeled mechanism-based irreversible inhibitors, clorgyline and L-deprenyl, respectively. In this article we introduce MAO and describe the development of these radiotracers and their translation from preclinical studies to the investigation of variables affecting MAO in the human brain and peripheral organs. C1 Brookhaven Natl Lab, Upton, NY 11973 USA. Natl Inst Drug Abuse, NIH, Bethesda, MD 20892 USA. RP Fowler, JS (reprint author), Brookhaven Natl Lab, Upton, NY 11973 USA. EM fowler@bnl.gov OI Logan, Jean/0000-0002-6993-9994 FU NCRR NIH HHS [M01RR10710]; NIBIB NIH HHS [EB2630]; NIDA NIH HHS [K 05 DA020001] NR 86 TC 38 Z9 39 U1 1 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1536-1632 J9 MOL IMAGING BIOL JI Mol. Imaging. Biol. PD NOV-DEC PY 2005 VL 7 IS 6 BP 377 EP 387 DI 10.1007/s11307-005-0016-1 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 996CE UT WOS:000234151200001 PM 16265597 ER PT J AU Valjavec-Gratian, M Henderson, TA Hill, TM AF Valjavec-Gratian, M Henderson, TA Hill, TM TI Tus-mediated arrest of DNA replication in Escherichia coli is modulated by DNA supercoiling SO MOLECULAR MICROBIOLOGY LA English DT Article ID R-LOOP FORMATION; TOPOISOMERASE-I; TERMINUS REGION; TER COMPLEX; CHROMOSOME; PROTEIN; MUTATIONS; TRANSCRIPTION; SEQUENCE; PLASMID AB In the absence of RecA, expression of the Tus protein of Escherichia coli is lethal when ectopic Ter sites are inserted into the chromosome in an orientation that blocks completion of chromosome replication. Using this observation as a basis for genetic selection, an extragenic suppressor of Tus-mediated arrest of DNA replication was isolated with diminished ability of Tus to halt DNA replication. Resistance to tus expression mapped to a mutation in the stop codon of the topA gene (topA869), generating an elongated topoisomerase I protein with a marked reduction in activity. Other alleles of topA with mutations in the carboxyl-terminal domain of topoisomerase I, topA10 and topA66, also rendered recA strains with blocking Ter sites insensitive to tus expression. Thus, increased negative supercoiling in the DNA of these mutants reduced the ability of Tus-Ter complexes to arrest DNA replication. The increase in superhelical density did not diminish replication arrest by disrupting Tus-Ter interactions, as Tus binding to Ter sites was essentially unaffected by the topA mutations. The topA869 mutation also relieved the requirement for recombination functions other than recA to restart replication, such as recC, ruvA and ruvC, indicating that the primary effect of the increased negative supercoiling was to interfere with Tus blockage of DNA replication. Introduction of gyrB mutations in combination with the topA869 mutation restored supercoiling density to normal values and also restored replication arrest at Ter sites, suggesting that supercoiling alone modulated Tus activity. We propose that increased negative supercoiling enhances DnaB unwinding activity, thereby reducing the duration of the Tus-DnaB interaction and leading to decreased Tus activity. C1 US Natl Lib Med, Natl Biotechnol Ctr, Bethesda, MD 20894 USA. Univ N Dakota, Sch Med, Dept Microbiol & Immunol, Grand Forks, ND 58202 USA. RP US Natl Lib Med, Natl Biotechnol Ctr, 8600 Rockville Pike, Bethesda, MD 20894 USA. EM tomhill@medicine.nodak.edu NR 51 TC 10 Z9 10 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0950-382X EI 1365-2958 J9 MOL MICROBIOL JI Mol. Microbiol. PD NOV PY 2005 VL 58 IS 3 BP 758 EP 773 DI 10.1111/j.1365-2958.2005.04860.x PG 16 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 973QG UT WOS:000232537100012 PM 16238625 ER PT J AU Skillman, KM Barnard, TJ Peterson, JH Ghirlando, R Bernstein, HD AF Skillman, KM Barnard, TJ Peterson, JH Ghirlando, R Bernstein, HD TI Efficient secretion of a folded protein domain by a monomeric bacterial autotransporter SO MOLECULAR MICROBIOLOGY LA English DT Article ID ESCHERICHIA-COLI; CONDUCTING CHANNEL; MEMBRANE; EXPORT; TRANSLOCATOR; BIOGENESIS; COMPLEX; INVITRO; BINDING; INVIVO AB Bacterial autotransporters are proteins that contain a small C-terminal 'beta domain' that facilitates translocation of a large N-terminal 'passenger domain' across the outer membrane (OM) by an unknown mechanism. Here we used EspP, an autotransporter produced by Escherichia coli O157:H7, as a model protein to gain insight into the transport reaction. Initially we found that the passenger domain of a truncated version of EspP (EspP Delta 1-851) was translocated efficiently across the OM. Blue Native polyacrylamide gel electrophoresis, analytical ultracentrifugation and other biochemical methods showed that EspP Delta 1-851 behaves as a compact monomer and strongly suggest that the channel formed by the beta domain is too narrow to accommodate folded polypeptides. Surprisingly, we found that a folded protein domain fused to the N-terminus of EspP Delta 1-851 was efficiently translocated across the OM. Further analysis revealed that the passenger domain of wild-type EspP also folds at least partially in the periplasm. To reconcile these data, we propose that the EspP beta domain functions primarily to target and anchor the protein and that an external factor transports the passenger domain across the OM. C1 NIDDKD, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA. NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Bernstein, HD (reprint author), NIDDKD, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA. EM harris_bernstein@nih.gov RI Ghirlando, Rodolfo/A-8880-2009 FU Intramural NIH HHS NR 31 TC 78 Z9 79 U1 0 U2 4 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD NOV PY 2005 VL 58 IS 4 BP 945 EP 958 DI 10.1111/j.1365-2958.2005.04885.x PG 14 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 978SR UT WOS:000232893800003 PM 16262782 ER PT J AU Touz, MC Conrad, JT Nash, TE AF Touz, MC Conrad, JT Nash, TE TI A novel palmitoyl acyl transferase controls surface protein palmitoylation and cytotoxicity in Giardia lamblia SO MOLECULAR MICROBIOLOGY LA English DT Article ID TERMINAL CYSTEINE RESIDUES; T-CELL-ACTIVATION; LIPID RAFTS; SECRETORY APPARATUS; ANTIGENIC VARIATION; GENE-EXPRESSION; IDENTIFICATION; ENCYSTATION; PARASITE; DOMAIN AB The intestinal protozoan parasite Giardia lamblia undergoes surface antigenic variation whereby one of a family of structurally related variant-specific surface proteins (VSPs) is replaced in a regulated process by another antigenically distinct VSP. All VSPs are type I membrane proteins that have a conserved hydrophobic sequence terminated by the invariant hydrophilic amino acids, CRGKA. Using transfected Giardia constitutively expressing HA-tagged VSPH7 and incubated with radioactive [H-3]palmitate, we demonstrate that the palmitate is attached to the Cys in the conserved CRGKA tail. Surface location of mutant VSPs lacking either the CRGKA tail or its Cys is identical to that of wild-type VSPH7 but non-palmitoylated mutants fail to undergo complement-independent antibody specific cytotoxicity. In addition, membrane localization of non-palmitoylated mutant VSPH7 changes from a pattern similar to rafts to non-rafts. Palmitoyl transferases (PAT), responsible for protein palmitoylation in other organisms, often possess a cysteine-rich domain containing a conserved DHHC motif (DHHC-CRD). An open reading frame corresponding to a putative 50 kDa Giardia PAT (gPAT) containing a DHHC-CRD motif was found in the Giardia genome database. Expression of epitope-tagged gPAT using a tetracycline inducible vector localized gPAT to the plasma membrane, a pattern similar to that of VSPs. Transfection with gPAT antisense producing vectors inhibits gPAT expression and palmitoylation of VSPs in vitro confirming the function of gPAT. These results show that VSPs are palmitoylated at the cysteine within the conserved tail by gPAT and indicate an essential function of palmitoylation in control of VSP-mediated signalling and processing. C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Nash, TE (reprint author), NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. EM tnash@niaid.nih.gov NR 46 TC 47 Z9 48 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD NOV PY 2005 VL 58 IS 4 BP 999 EP 1011 DI 10.1111/j.1365-2958.2005.04891.x PG 13 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 978SR UT WOS:000232893800007 PM 16262786 ER PT J AU Andoh, T Chock, PB Murphy, DL Chiueh, CC AF Andoh, T Chock, PB Murphy, DL Chiueh, CC TI Role of the redox protein thioredoxin in cytoprotective mechanism evoked by (-)-deprenyl SO MOLECULAR PHARMACOLOGY LA English DT Article ID STRESS-INDUCED APOPTOSIS; MONOAMINE-OXIDASE-B; SUPEROXIDE-DISMUTASE; GLUTATHIONE-PEROXIDASE; PARKINSONS-DISEASE; OXIDATIVE STRESS; DOPAMINERGIC TOXICITY; DEPRENYL PROTECTS; NEUROTOXICITY; NEURONS AB Through the inhibition of monoamine oxidase type B (MAO-B), (-)-deprenyl (selegiline) prevents the conversion of 1-methyl-4- phenyl-1,2,3,6-tetrahydropyridine (MPTP) to the toxic metabolite 1-methyl-4- phenylpyridinium ion (MPP+) and also prevents the neurotoxicity in the dopaminergic neurons in animal models. Cumulative observations suggest that selegiline may also protect against MPP+-induced neurotoxicity, possibly through the induction of pro-survival genes. We have observed that thioredoxin (Trx) mediates the induction of mitochondrial manganese superoxide dismutase (MnSOD) and Bcl-2 during preconditioning-induced hormesis. We therefore investigated whether the redox protein Trx plays any role in the neuroprotective mechanism of selegiline against MPP+-induced cytotoxicity in human SH-SY5Y neuroblastoma cells and also in primary neuronal cultures of mouse midbrain dopaminergic neurons. After confirming that selegiline protects against MPP+-induced cytotoxicity, we observed further that selegiline, at 1 mu M or less, induced Trx for protection against oxidative injury caused by MPP+. The induction of Trx was blocked by protein kinase A (PKA) inhibitor and mediated by a PKA-sensitive phospho-activation of mitogen-activated protein (MAP) kinase Erk1/2 and the transcription factor c-Myc. Selegiline-induced Trx and associated neuroprotection were concomitantly blocked by the antisense against Trx mRNA, but not the sense or antisense mutant phosphothionate oligonucleotides, not only in human SH-SY5Y cells but also in mouse primary neuronal culture of midbrain dopaminergic neurons. Furthermore, the redox cycling of Trx may mediate the protective action of selegiline because the inhibition of Trx reductase by 1-chloro-2,4-dinitrobenzene ameliorated the effect of selegiline. Trx (1 mu M) consistently increased the expression of mitochondrial proteins MnSOD and Bcl-2, supporting cell survival (Andoh et al., 2002). In conclusion, without modifying MAO-B activity, selegiline augments the gene induction of Trx, leading to elevated expression of antioxidative MnSOD and antiapoptotic Bcl-2 proteins for protecting against MPP+-induced neurotoxicity. C1 Taipei Med Univ, Sch Pharm, Ctr Brain Dis & Aging, Taipei 110, Taiwan. NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA. NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. Toyama Med & Pharmaceut Univ, Dept Appl Pharmacol, Toyama, Japan. RP Chiueh, CC (reprint author), Taipei Med Univ, Sch Pharm, Ctr Brain Dis & Aging, 250 Wu Xing St, Taipei 110, Taiwan. EM chiueh@tmu.edu.tw NR 40 TC 18 Z9 22 U1 0 U2 5 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD NOV PY 2005 VL 68 IS 5 BP 1408 EP 1414 DI 10.1124/mol.105.012302 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 977VZ UT WOS:000232832900021 PM 16099847 ER PT J AU Meshorer, E Bryk, B Toiber, D Cohen, J Podoly, E Dori, A Soreq, H AF Meshorer, E Bryk, B Toiber, D Cohen, J Podoly, E Dori, A Soreq, H TI SC35 promotes sustainable stress-induced alternative splicing of neuronal acetylcholinesterase mRNA SO MOLECULAR PSYCHIATRY LA English DT Article DE SC35; stress; acetylcholinesterase; alternative splicing; ASF/SF2 ID AMYOTROPHIC-LATERAL-SCLEROSIS; PREFRONTAL CORTEX; HNRNP A1; IN-VIVO; GENE-EXPRESSION; SR PROTEINS; CELLS; BINDING; TRANSCRIPTION; HIPPOCAMPUS AB Long-lasting alternative splicing of neuronal acetylcholinesterase (AChE) pre-mRNA occurs during neuronal development and following stress, altering synaptic properties. To explore the corresponding molecular events, we sought to identify mRNAs encoding for abundant splicing factors in the prefrontal cortex (PFC) following stress. Here we show elevated levels of the splicing factor SC35 in stressed as compared with naive mice. In cotransfections of COS-1 and HEK293 cells with an AChE minigene allowing 30 splice variations, SC35 facilitated a shift from the primary AChE-S to the stress-induced AChE-R variant, while ASF/SF2 caused the opposite effect. Transfection with chimeric constructs comprising of SC35 and ASF/SF2 RRM/RS domains identified the SC35 RRM as responsible for AChE mRNA's alternative splicing. In poststress PFC neurons, increased SC35 mRNA and protein levels coincided with selective increase in AChE-R mRNA. In the developing mouse embryo, cortical progenitor cells in the ventricular zone displayed transient SC35 elevation concomitant with dominance of AChE-R over AChE-S mRNA. Finally, transgenic mice overexpressing human AChE-R, but not those overexpressing AChE-S, showed significant elevation in neuronal SC35 levels, suggesting a reciprocal reinforcement process. Together, these findings point to an interactive relationship of SC35 with cholinergic signals in the long-lasting consequences of stress on nervous system plasticity and development. C1 Hebrew Univ Jerusalem, Dept Biol Chem, Jerusalem, Israel. Soroka Univ Med Ctr, Dept Neurol, Beer Sheva, Israel. Hebrew Univ Jerusalem, Wolfson Ctr Struct Biol, Jerusalem, Israel. RP Meshorer, E (reprint author), NCI, NIH, 41 Lib Dr, Bethesda, MD 20892 USA. EM meshoree@mail.nih.gov; soreq@cc.huji.ac.il NR 59 TC 60 Z9 60 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD NOV PY 2005 VL 10 IS 11 BP 985 EP 997 DI 10.1038/sj.mp.4001735 PG 13 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 977WA UT WOS:000232833000005 PM 16116489 ER PT J AU Ghosh, MP Zigler, JS AF Ghosh, MP Zigler, JS TI Lack of fiber cell induction stops normal growth of rat lenses in organ culture SO MOLECULAR VISION LA English DT Article ID SERUM-FREE MEDIUM; PROTEIN-SYNTHESIS; OCULAR LENS; PDGF AB Purpose: Lens organ culture has been widely used as a model system for studying cataract induction and prevention. While rat lenses remain transparent and viable for a week or longer in culture, they do not increase in weight. This study was undertaken to determine what accounts for the lack of weight increase. Methods: Lenses from 4-week-old Sprague-Dawley rats were cultured using standard methods. Histological analysis was performed on sections from methacrylate embedded tissue. S-35-labeled amino acids were used to metabolically label lenses in culture for the purpose of analyzing protein synthesis. BrdU labeling was used to assess synthesis of DNA in vivo and in vitro. Results: Lenses from young, rapidly growing rats do not increase in weight after being put into organ culture. Protein synthesis continues in the cultured lenses although at decreased levels as time in culture increases. Lens epithelial cells continue to synthesize DNA as indicated by BrdU labeling, however, the normal migration of epithelial cells from the proliferative zone to the equator does not occur in culture. In the cultured lens, the shape of the lens bow gradually changes, becoming compressed towards the capsule. Conclusions: The differentiation of lens epithelial cells into fibers is arrested in the cultured lens; consequently lenses in organ culture do not grow normally. C1 NEI, Lens & Cataract Biol Sect, Bethesda, MD 20892 USA. RP Zigler, JS (reprint author), NEI, Lens & Cataract Biol Sect, 7 Mem Dr,MSC 0703, Bethesda, MD 20892 USA. EM ziglers@nei.nih.gov FU Intramural NIH HHS NR 20 TC 2 Z9 2 U1 0 U2 0 PU MOLECULAR VISION PI ATLANTA PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E, ATLANTA, GA 30322 USA SN 1090-0535 J9 MOL VIS JI Mol. Vis. PD NOV 1 PY 2005 VL 11 IS 106-7 BP 901 EP 908 PG 8 WC Biochemistry & Molecular Biology; Ophthalmology SC Biochemistry & Molecular Biology; Ophthalmology GA 982DJ UT WOS:000233137800002 PM 16280975 ER PT J AU Chaverri, P Bischoff, JF Evans, HC Hodge, KT AF Chaverri, P Bischoff, JF Evans, HC Hodge, KT TI Regiocrella, a new entomopathogenic genus with a pycnidial anamorph and its phylogenetic placement in the Clavicipitaceae SO MYCOLOGIA LA English DT Article DE ascomycota; evolution; Hypocreales; molecular phylogenetics; systematics ID VERTICILLIUM SECT. PROSTRATA; SP-NOV; INFERENCE; HYPOCREALES; CLAVICEPS; EVOLUTION; EPICHLOE; REVISION; INSECTS; FUNGUS AB A new genus, Regiocrella, is described with two species, R. camerunensis and R. sinensis, based oil specimens collected in Cameroon and China. Both species are parasitic on scale insects (Coccidae, Homoptera). Morphological and molecular evidence place the new genus ill the Clavicipitaceae (Hypocreales), despite its combination of characters that are atypical of that family; Regiocrella is characterized by having perithecia partly immersed in a subiculum, noncapitate asci, unicellular fusiform ascospores and pycnidial-acervular conidiomata. The two new species, R. camerunensis and R. sinensis, are distinguished based on ascospore and perithecium size. Morphological characters were evaluated and compared to other genera in the Clavicipitaceae, especially those parasitic oil scale insects or with pycnidial-acervular anamorphs or synanamorphs (i.e. Aschersonia, Ephelis or Sphacelia): Atkinsonella, Balansia, Claviceps, Epichloe, Hypocrella, Myriogenospora and Neoclaviceps. The phylogenetic relationships of Regiocrella were examined with three gene loci: large Subunit nuclear ribosomal DNA (LSU), translation elongation factor 1-alpha (TEF), and RNA polymerase II subunit I (PPB1). The results of this study Confirm that Regiocrella is distinct from other genera in the Clavicipitaceae and that its two species form a monophyletic group. Regiocrella is shown to be closely related to the scale insect pathogen Hypocrella, and the plant-associated genera Balansia, Claviceps, Epichloe, Myriogenospora and Neoclaviceps. This study also provides insights into the evolution of pycnidial-acervular conidiomata and scale insect parasitism within the Clavicipitaceae. Plant-associated genera form a monophyletic group correlated with Clavicipitaceae subfamily Clavicipitoideae sensu Diehl. We also demonstrate that scale insect parasites have multiple evolutionary origins within the family and genera with pycniclial-acervular anamorphs or synanamorphs have a single origin. C1 Cornell Univ, Dept Plant Pathol, Ithaca, NY 14853 USA. NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. CABI Biosci UK Ctr Ascot, Ascot SL5 7TA, Berks, England. RP Chaverri, P (reprint author), Howard Univ, Dept Biol, 415 Coll St NW, Washington, DC 20059 USA. EM pchaverri@howard.edu OI Chaverri, Priscila/0000-0002-8486-6033 NR 44 TC 17 Z9 18 U1 0 U2 5 PU ALLEN PRESS INC PI LAWRENCE PA 810 E 10TH ST, LAWRENCE, KS 66044 USA SN 0027-5514 J9 MYCOLOGIA JI Mycologia PD NOV-DEC PY 2005 VL 97 IS 6 BP 1225 EP 1237 DI 10.3852/mycologia.97.6.1225 PG 13 WC Mycology SC Mycology GA 042JS UT WOS:000237524800007 PM 16722216 ER PT J AU Chaverri, P Bischoff, JF Liu, M Hodge, KT AF Chaverri, P Bischoff, JF Liu, M Hodge, KT TI A new species of Hypocrella, H-macrostroma, and its phylogenetic relationships to other species with large stromata SO MYCOLOGICAL RESEARCH LA English DT Article ID INFERENCE; EVOLUTION; SETS AB Two specimens of a new species of Hypocrella with large stromata were collected in Bolivia and Costa Rica. The morphology of the new species, H. macrostroma sp. nov., was compared with that of other species with large stromata, i.e. H africana, H. gaertneriana, and H. schizostachyi. In addition, phylogenetic analyses of partial sequences from three genes, large subunit nuclear ribosomal DNA (LSU), translation elongation factor 1-alpha (EF1-alpha), and RNA polymerase II subunit 1 (RPB1), were conducted to determine the relationships of the new species to other species of Hypocrella/ Aschersonia. Phylogenetic analyses show that H. macrostroma belongs to a strongly supported clade that includes H. africana, H. schizostachyi, and Aschersonia insperata, whereas other Hypocrella species belong to two sister clades. Hypocrella macrostroma is described and illustrated, and a lectotype is designated for H. gaertneriana. C1 Cornell Univ, Dept Plant Pathol, Ithaca, NY 14853 USA. NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Chaverri, P (reprint author), USDA ARS, Systemat Bot & Mycol Lab, Rm 304,B-011A,10300 Baltimore Ave, Beltsville, MD 20705 USA. EM priscila@nt.ars-grin.gov OI Chaverri, Priscila/0000-0002-8486-6033 NR 26 TC 12 Z9 12 U1 0 U2 3 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4211 USA SN 0953-7562 J9 MYCOL RES JI Mycol. Res. PD NOV PY 2005 VL 109 BP 1268 EP 1275 DI 10.1017/S0953756205003904 PN 11 PG 8 WC Mycology SC Mycology GA 979UU UT WOS:000232971300009 PM 16279420 ER PT J AU Ross, ED Minton, A Wickner, RB AF Ross, ED Minton, A Wickner, RB TI Prion domains: sequences, structures and interactions SO NATURE CELL BIOLOGY LA English DT Review ID SOLID-STATE NMR; CREUTZFELDT-JAKOB-DISEASE; CHAPERONE PROTEIN HSP104; BETA-AMYLOID FIBRILS; YEAST SUP35 PROTEIN; PRP KNOCKOUT MICE; SACCHAROMYCES-CEREVISIAE; PSI(+) PRION; IN-VITRO; PODOSPORA-ANSERINA AB Mammalian and most fungal infectious proteins ( also known as prions) are self-propagating amyloid, a filamentous beta- sheet structure. A prion domain determines the infectious properties of a protein by forming the core of the amyloid. We compare the properties of known prion domains and their interactions with the remainder of the protein and with chaperones. Ure2p and Sup35p, two yeast prion proteins, can still form prions when the prion domains are shuffled, indicating a parallel in-register beta- sheet structure. C1 NIDDKD, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. RP Ross, ED (reprint author), Colorado State Univ, Dept Biochem & Mol Biol, Ft Collins, CO 80523 USA. EM wickner@helix.nih.gov OI Ross, Eric/0000-0002-6473-9977; Minton, Allen/0000-0001-8459-1247 NR 100 TC 82 Z9 84 U1 2 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD NOV PY 2005 VL 7 IS 11 BP 1039 EP 1044 DI 10.1038/ncb1105-1039 PG 6 WC Cell Biology SC Cell Biology GA 979GM UT WOS:000232930400001 PM 16385730 ER PT J AU Mattson, MP Cutler, RG Jo, DG AF Mattson, MP Cutler, RG Jo, DG TI Alzheimer peptides perturb lipid-regulating enzymes SO NATURE CELL BIOLOGY LA English DT Editorial Material ID C-DISEASE; CERAMIDE; SPHINGOMYELINASE; CHOLESTEROL; ACTIVATION AB An increase in the size of the amyloid beta-peptide (A beta 42 versus A beta 40) may be a key factor in the pathogenesis of Alzheimer's disease. By altering the activities of enzymes involved in the metabolism of cholesterol and sphingomyelin, an increase in the A beta 42: A beta 40 ratio may cause dysfunction and death of neurons. C1 NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. RP Mattson, MP (reprint author), NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. EM mattsonm@grc.nia.nih.gov RI Mattson, Mark/F-6038-2012 NR 16 TC 21 Z9 23 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD NOV PY 2005 VL 7 IS 11 BP 1045 EP 1047 DI 10.1038/ncb1105-1045 PG 3 WC Cell Biology SC Cell Biology GA 979GM UT WOS:000232930400002 PM 16385731 ER PT J AU Ishitani, T Matsumoto, K Chitnis, AB Itoh, M AF Ishitani, T Matsumoto, K Chitnis, AB Itoh, M TI Nrarp functions to modulate neural-crest-cell differentiation by regulating LEF1 protein stability SO NATURE CELL BIOLOGY LA English DT Article ID ANKYRIN-REPEAT PROTEIN; SIGNALING PATHWAY; ZEBRAFISH; EXPRESSION; HOMOLOG; FATE; DOMAIN; NOTCH1; DELTA AB Nrarp (Notch-regulated ankyrin repeat protein) is a small protein that has two ankyrin repeats(1-5). Although Nrarp is known to be an inhibitory component of the Notch signalling pathway that operates in different developmental processes(1,2,4,5), the in vivo roles of Nrarp have not been fully characterized. Here, we show that Nrarp is a positive regulator in the Wnt signalling pathway. In zebrafish, knockdown of Nrarp-a expression by an antisense morpholino oligonucleotide (MO) results in altered Wnt-signalling-dependent neural-crest-cell development. Nrarp stabilizes LEF1 protein, a pivotal transcription factor in the Wnt signalling cascade, by blocking LEF1 ubiquitination. In accordance with this, the knockdown phenotype of lef1 is similar to that of nrarp-a, at least in part, in its effect on the development of multiple tissues in zebrafish. Furthermore, activation of LEF1 does not affect Notch activity or vice versa. These findings reveal that Nrarp independently regulates canonical Wnt and Notch signalling by modulating LEF1 and Notch protein turnover, respectively. C1 Nagoya Univ, Grad Sch Sci, Div Biol Sci, Lab Cell Regulat,Unit Nervous Syst Dev, Nagoya, Aichi 4648602, Japan. Nagoya Univ, Grad Sch Sci, Div Biol Sci, Lab Cell Regulat,Grp Signal Transduct,Chikusa Ku, Nagoya, Aichi 4648602, Japan. Japan Sci & Technol Corp, CREST, Chikusa Ku, Nagoya, Aichi 4648602, Japan. NICHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. RP Itoh, M (reprint author), Nagoya Univ, Grad Sch Sci, Div Biol Sci, Lab Cell Regulat,Unit Nervous Syst Dev, Nagoya, Aichi 4648602, Japan. EM mito@bunshi3.bio.nagoya-u.ac.jp RI Ishitani, Tohru/E-9781-2014 NR 26 TC 45 Z9 50 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD NOV PY 2005 VL 7 IS 11 BP 1106 EP 1112 DI 10.1038/ncb1311 PG 7 WC Cell Biology SC Cell Biology GA 979GM UT WOS:000232930400014 PM 16228014 ER PT J AU Gladwin, MT Schechter, AN Kim-Shapiro, DB Patel, RP Hogg, N Shiva, S Cannon, RO Kelm, M Wink, DA Espey, MG Oldfield, EH Pluta, RM Freeman, BA Lancaster, JR Feelisch, M Lundberg, JO AF Gladwin, MT Schechter, AN Kim-Shapiro, DB Patel, RP Hogg, N Shiva, S Cannon, RO Kelm, M Wink, DA Espey, MG Oldfield, EH Pluta, RM Freeman, BA Lancaster, JR Feelisch, M Lundberg, JO TI The emerging biology of the nitrite anion SO NATURE CHEMICAL BIOLOGY LA English DT Article ID OXIDE SYNTHASE ACTIVITY; REGIONAL BLOOD-FLOW; RELAXING FACTOR; IN-VIVO; ISCHEMIA-REPERFUSION; NITROLINOLEIC ACID; GUANYLATE-CYCLASE; L-ARGININE; NITRATE; HEMOGLOBIN AB Nitrite has now been proposed to play an important physiological role in signaling, blood flow regulation and hypoxic nitric oxide homeostasis. A recent two-day symposium at the US National Institutes of Health highlighted recent advances in the understanding of nitrite biochemistry, physiology and therapeutics. C1 NHLBI, Vasc Med Branch, Bethesda, MD 20892 USA. NIH, Ctr Clin, Dept Crit Care Med, Bethesda, MD 20892 USA. NIDDKD, Bethesda, MD USA. Wake Forest Univ, Dept Phys, Winston Salem, NC 27109 USA. Univ Alabama, Birmingham, AL USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. NHLBI, Vasc Med Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Cardiovasc Branch, NIH, Bethesda, MD 20892 USA. Univ Dusseldorf, D-4000 Dusseldorf, Germany. NCI, NIH, Bethesda, MD 20892 USA. NINDS, Special Neurol Branch, NIH, Bethesda, MD 20892 USA. Univ Pittsburgh, Sch Med, Dept Pharmacol, Pittsburgh, PA 15261 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden. RP Gladwin, MT (reprint author), NHLBI, Vasc Med Branch, Bldg 10, Bethesda, MD 20892 USA. EM mgladwin@nih.gov RI Freeman, Bruce/H-9342-2012; Feelisch, Martin/C-3042-2008; OI Feelisch, Martin/0000-0003-2320-1158; Schechter, Alan N/0000-0002-5235-9408; Patel, Rakesh/0000-0002-1526-4303 NR 57 TC 366 Z9 373 U1 3 U2 35 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1552-4450 J9 NAT CHEM BIOL JI Nat. Chem. Biol. PD NOV PY 2005 VL 1 IS 6 BP 308 EP 314 DI 10.1038/nchembio1105-308 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 979GH UT WOS:000232929900004 PM 16408064 ER PT J AU Wellems, TE Fairhurst, RM AF Wellems, TE Fairhurst, RM TI Malaria-protective traits at odds in Africa? SO NATURE GENETICS LA English DT Editorial Material ID POPULATION-GENETICS; CHILDREN AB Sickle hemoglobin and alpha-thalassemia evolved as two of the most common human genetic polymorphisms because they confer protection against malaria. New evidence suggests that their effects may interfere with each other, raising questions about these hemoglobinopathies and their mechanisms of protection. C1 NIAID, Lab Malaria & Vector Res, Bethesda, MD 20892 USA. RP Wellems, TE (reprint author), NIAID, Lab Malaria & Vector Res, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM twellems@niaid.nih.gov NR 15 TC 5 Z9 5 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD NOV PY 2005 VL 37 IS 11 BP 1160 EP 1162 DI 10.1038/ng1105-1160 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 980VB UT WOS:000233045200004 PM 16254557 ER PT J AU Wynn, TA AF Wynn, TA TI T-H-17: a giant step from T(H)1 and T(H)2 SO NATURE IMMUNOLOGY LA English DT Editorial Material ID AUTOIMMUNE INFLAMMATION; IL-23; INTERLEUKIN-17; CYTOKINE; RECEPTOR; DISTINCT; IL-12; MICE C1 NIAID, NIH, Bethesda, MD 20892 USA. RP Wynn, TA (reprint author), NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM twynn@niaid.nih.gov RI Wynn, Thomas/C-2797-2011 NR 12 TC 103 Z9 115 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD NOV PY 2005 VL 6 IS 11 BP 1069 EP 1070 DI 10.1038/ni1105-1069 PG 3 WC Immunology SC Immunology GA 977WD UT WOS:000232833300004 PM 16239919 ER PT J AU Tolar, P Sohn, HW Pierce, SK AF Tolar, P Sohn, HW Pierce, SK TI The initiation of antigen-induced B cell antigen receptor signaling viewed in living cells by fluorescence resonance energy transfer SO NATURE IMMUNOLOGY LA English DT Article ID LIPID RAFTS; CYTOPLASMIC DOMAIN; LIVE CELLS; TRANSDUCTION; FRET; ACTIVATION; PROTEIN; PHOSPHORYLATION; LYMPHOCYTES; INHIBITION AB Binding of antigen to the B cell antigen receptor (BCR) triggers signaling that ultimately leads to B cell activation. Using quantitative fluorescence resonance energy transfer imaging, we provide evidence here that the BCR is a monomer on the surface of resting cells. Binding of multivalent antigen clustered the BCR, resulting in the simultaneous phosphorylation of and a conformational change in the BCR cytoplasmic domains from a closed to an open form. Notably, the open conformation required immunoreceptor tyrosine-activation motif and continuous Src family kinase activity but not binding of the kinase Syk. Thus, the initiation of BCR signaling is a very dynamic process accompanied by reversible conformational changes induced by Src family kinase activity. C1 NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. RP Pierce, SK (reprint author), NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. EM spierce@nih.gov FU Intramural NIH HHS NR 41 TC 135 Z9 139 U1 2 U2 15 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD NOV PY 2005 VL 6 IS 11 BP 1168 EP 1176 DI 10.1038/ni1262 PG 9 WC Immunology SC Immunology GA 977WD UT WOS:000232833300018 PM 16200067 ER PT J AU Cookson, MR AF Cookson, MR TI Neurons inflict self-harm SO NATURE MEDICINE LA English DT Editorial Material ID SPORADIC PARKINSONS-DISEASE; ALPHA-SYNUCLEIN; S-NITROSYLATION; STRESS C1 NIA, Cell Biol & Gene Express Unit, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. RP Cookson, MR (reprint author), NIA, Cell Biol & Gene Express Unit, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. EM cookson@mail.nih.gov NR 11 TC 2 Z9 2 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD NOV PY 2005 VL 11 IS 11 BP 1159 EP 1161 DI 10.1038/nm1105-1159 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 981VF UT WOS:000233115400023 PM 16270070 ER PT J AU Zhang, H Chua, KS Guimond, M Kapoor, V Brown, MV Fleisher, TA Long, LM Bernstein, D Hill, BJ Douek, DC Berzofsky, JA Carter, CS Read, EJ Helman, LJ Mackall, CL AF Zhang, H Chua, KS Guimond, M Kapoor, V Brown, MV Fleisher, TA Long, LM Bernstein, D Hill, BJ Douek, DC Berzofsky, JA Carter, CS Read, EJ Helman, LJ Mackall, CL TI Lymphopenia and interleukin-2 therapy alter homeostasis of CD4(+) CD25(+) regulatory T cells SO NATURE MEDICINE LA English DT Article ID HIV-INFECTED PATIENTS; TUMOR-IMMUNITY; AUTOIMMUNITY; MICE; TOLERANCE; FOXP3; SELF; TRANSPLANTATION; RECONSTITUTION; EXPANSION AB CD4(+)CD25(+) regulatory T ( T-reg) cells have a crucial role in maintaining immune tolerance. Mice and humans born lacking Treg cells develop severe autoimmune disease(1,2), and depletion of Treg cells in lymphopenic mice induces autoimmunity(3,4). Interleukin ( IL)-2 signaling is required for thymic development(5), peripheral expansion(6) and suppressive activity of T(reg)cells(7). Animals lacking IL-2 die of autoimmunity(8,9), which is prevented by administration of IL-2-responsive T(reg)cells(5). In light of the emerging evidence that one of the primary physiologic roles of IL-2 is to generate and maintain T-reg cells(10), the question arises as to the effects of IL-2 therapy on them. We monitored Treg cells during immune reconstitution in individuals with cancer who did or did not receive IL-2 therapy. CD4(+)CD25(hi) cells underwent homeostatic peripheral expansion during immune reconstitution, and in lymphopenic individuals receiving IL-2, the T-reg cell compartment was markedly increased. Mouse studies showed that IL-2 therapy induced expansion of existent T-reg cells in normal hosts, and IL-2 induced T-reg cell expansion was further augmented by lymphopenia. On a per-cell basis, T-reg cells generated by IL-2 therapy expressed similar levels of FOXP3 and had similar potency for suppression compared to Treg cells present in normal hosts. These studies suggest that IL-2 and lymphopenia are primary modulators of CD4(+)CD25(+) T-reg cell homeostasis. C1 NIH, Pediat Oncol Branch, Bethesda, MD 20892 USA. NIH, Expt Transplantat & Immunol Branch, Canc Res Ctr, Bethesda, MD 20892 USA. NIH, Ctr Clin, Dept Lab Med, Bethesda, MD 20892 USA. NIAID, Vaccine Res Ctr, Bethesda, MD 20892 USA. NIH, Vaccine Branch, Canc Res Ctr, Bethesda, MD 20892 USA. NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. RP Mackall, CL (reprint author), NIH, Pediat Oncol Branch, 10 Ctr Dr, Bethesda, MD 20892 USA. EM cm35c@nih.gov FU Intramural NIH HHS NR 31 TC 263 Z9 279 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD NOV PY 2005 VL 11 IS 11 BP 1238 EP 1243 DI 10.1038/nm1312 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 981VF UT WOS:000233115400037 PM 16227988 ER PT J AU Shaham, Y Hope, BT AF Shaham, Y Hope, BT TI The role of neuroadaptations in relapse to drug seeking SO NATURE NEUROSCIENCE LA English DT Editorial Material ID MESOLIMBIC DOPAMINE SYSTEM; STRESS-INDUCED RELAPSE; COCAINE-SEEKING; NEUROTROPHIC FACTOR; ADDICTION; SENSITIZATION; WITHDRAWAL; INCUBATION; EXPRESSION; GLUTAMATE AB One of the most difficult problems in treating addiction is not withdrawing addicts from drugs, but preventing relapse. Persistent neuroadaptations are thought to underlie aspects of addiction, including relapse. This commentary assesses the degree to which these neuroadaptations, primarily identified in preclinical studies on cocaine, induce relapse. C1 NIDA, Behav Neurosci Branch, Intramural Res Program, NIH,Dept Hlth & Human Serv, Baltimore, MD 21224 USA. RP Shaham, Y (reprint author), NIDA, Behav Neurosci Branch, Intramural Res Program, NIH,Dept Hlth & Human Serv, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM yshaham@intra.nida.nih.gov RI Hope, Bruce/A-9223-2010; shaham, yavin/G-1306-2014 OI Hope, Bruce/0000-0001-5804-7061; FU Intramural NIH HHS NR 30 TC 76 Z9 78 U1 1 U2 12 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD NOV PY 2005 VL 8 IS 11 BP 1437 EP 1439 DI 10.1038/nn1105-1437 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 979TB UT WOS:000232966600011 PM 16251983 ER PT J AU Lovinger, DM Crabbe, JC AF Lovinger, DM Crabbe, JC TI Laboratory models of alcoholism: treatment target identification and insight into mechanisms SO NATURE NEUROSCIENCE LA English DT Review ID CHRONIC ETHANOL EXPOSURE; BINDING-PROTEIN LUSH; DROSOPHILA-MELANOGASTER; SEROTONIN TRANSPORTER; GABA(A) RECEPTORS; MOTOR IMPAIRMENT; C57BL/6J MICE; HIPPOCAMPAL-NEURONS; GENETIC GENOMICS; MOUSE BEHAVIOR AB Laboratory models, including animal tissues and live animals, have proven useful for discovery of molecular targets of alcohol action as well as for characterization of genetic and environmental factors that influence alcohol's neural actions. Here we consider strengths and weaknesses of laboratory models used in alcohol research and analyze the limitations of using animals to model a complex human disease. We describe targets for the neural actions of alcohol, and we review studies in which animal models were used to examine excessive alcohol drinking and to discover genes that may contribute to risk for alcoholism. Despite some limitations of the laboratory models used in alcohol research, these experimental approaches are likely to contribute to the development of new therapies for alcohol abuse and alcoholism. C1 NIAAA, Lab Integrat Neurosci, NIH, Rockville, MD 20852 USA. Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97239 USA. Portland Alcohol Res Ctr, Portland, OR USA. Dept Vet Affairs Med Ctr, Portland, OR USA. RP Lovinger, DM (reprint author), NIAAA, Lab Integrat Neurosci, NIH, Rockville, MD 20852 USA. EM lovindav@mail.nih.gov FU Intramural NIH HHS; NIAAA NIH HHS [AA10760, AA12714, AA13519, P60 AA010760] NR 100 TC 61 Z9 62 U1 3 U2 8 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD NOV PY 2005 VL 8 IS 11 BP 1471 EP 1480 DI 10.1038/nn1581 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 979TB UT WOS:000232966600018 PM 16251990 ER PT J AU Rouach, N Byrd, K Petralia, RS Elias, GM Adesnik, H Tomita, S Karimzadegan, S Kealey, C Bredt, DS Nicoll, RA AF Rouach, N Byrd, K Petralia, RS Elias, GM Adesnik, H Tomita, S Karimzadegan, S Kealey, C Bredt, DS Nicoll, RA TI TARP gamma-8 controls hippocampal AMPA receptor number, distribution and synaptic plasticity SO NATURE NEUROSCIENCE LA English DT Article ID CALCIUM-CHANNEL SUBUNITS; LONG-TERM POTENTIATION; EXCITATORY SYNAPSES; ENDOPLASMIC-RETICULUM; GLUTAMATE RECEPTORS; KAINATE RECEPTORS; MOUSE STARGAZER; CA2+ CHANNELS; MUTANT MOUSE; GENE FAMILY AB Synaptic plasticity involves activity-dependent trafficking of AMPA-type glutamate receptors. Numerous cytoplasmic scaffolding proteins are postulated to control AMPA receptor trafficking, but the detailed mechanisms remain unclear. Here, we show that the transmembrane AMPA receptor regulatory protein (TARP) gamma-8, which is preferentially expressed in the mouse hippocampus, is important for AMPA receptor protein levels and extrasynaptic surface expression. By controlling the number of AMPA receptors, gamma-8 is also important in long-term potentiation, but not long-term depression. This study establishes gamma-8 as a critical protein for basal AMPA receptor expression and localization at extrasynaptic sites in the hippocampus and raises the possibility that TARP-dependent control of AMPA receptors during synapse development and plasticity may be widespread. C1 Univ Calif San Francisco, Dept Mol & Cellular Pharmacol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94143 USA. Natl Inst Deafness & Other Commun Disorders, Neurochem Lab, NIH, Bethesda, MD 20892 USA. RP Nicoll, RA (reprint author), Univ Calif San Francisco, Dept Mol & Cellular Pharmacol, San Francisco, CA 94143 USA. EM nicoll@cmp.ucsf.edu FU Intramural NIH HHS NR 42 TC 135 Z9 140 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD NOV PY 2005 VL 8 IS 11 BP 1525 EP 1533 DI 10.1038/nn1551 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 979TB UT WOS:000232966600027 PM 16222232 ER PT J AU Brown, SL Joseph, J Stopfer, M AF Brown, SL Joseph, J Stopfer, M TI Encoding a temporally structured stimulus with a temporally structured neural representation SO NATURE NEUROSCIENCE LA English DT Article ID PRIMARY AUDITORY-CORTEX; LOCUST ANTENNAL LOBE; OLFACTORY SYSTEM; ODOR PLUMES; MANDUCA-SEXTA; PHEROMONE; RESPONSES; NEURONS; DISCRIMINATION; OSCILLATIONS AB Sensory neural systems use spatiotemporal coding mechanisms to represent stimuli. These time-varying response patterns sometimes outlast the stimulus. Can the temporal structure of a stimulus interfere with, or even disrupt, the spatiotemporal structure of the neural representation? We investigated this potential confound in the locust olfactory system. When odors were presented in trains of nearly overlapping pulses, responses of first-order interneurons (projection neurons) changed reliably, and often markedly, with pulse position as responses to one pulse interfered with subsequent responses. However, using the responses of an ensemble of projection neurons, we could accurately classify the odorants as well as characterize the temporal properties of the stimulus. Further, we found that second-order follower neurons showed firing patterns consistent with the information in the projection-neuron ensemble. Thus, ensemble-based spatiotemporal coding could disambiguate complex and potentially confounding temporally structured sensory stimuli and thereby provide an invariant response to a stimulus presented in various ways. C1 NICHHD, US Natl Inst Hlth, Bethesda, MD 20892 USA. RP Stopfer, M (reprint author), NICHHD, US Natl Inst Hlth, Bldg 35,Room 3A-102, Bethesda, MD 20892 USA. EM stopferm@mail.nih.gov FU Intramural NIH HHS NR 49 TC 82 Z9 83 U1 1 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD NOV PY 2005 VL 8 IS 11 BP 1568 EP 1576 DI 10.1038/nn1559 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 979TB UT WOS:000232966600032 PM 16222230 ER PT J AU Chang, KT Min, KT AF Chang, KT Min, KT TI Drosophila melanogaster homolog of Down syndrome critical region 1 is critical for mitochondrial function SO NATURE NEUROSCIENCE LA English DT Article ID ADENINE-NUCLEOTIDE TRANSLOCATOR; OXIDATIVE STRESS; ALZHEIMERS-DISEASE; SUPEROXIDE PRODUCTION; INHIBITS CALCINEURIN; DSCR1 ADAPT78; MOUSE MODELS; PROTEIN; GENE; PHOSPHORYLATION AB Mitochondrial dysfunction has emerged as a common theme that underlies numerous neurological disorders, including Down syndrome. Down syndrome cultures and tissues show mitochondrial damage such as impaired mitochondrial enzyme activities, defective mitochondrial DNA repairs and accumulation of toxic free radicals, but the cause of mitochondrial dysfunction remains elusive. Here we demonstrate that the Drosophila melanogaster homolog of human Down syndrome critical region gene 1 (DSCR1), nebula (also known as sarah, sra), has a crucial role in the maintenance of mitochondrial function and integrity. We report that nebula protein is located in the mitochondria. An alteration in the abundance of nebula affects mitochondrial enzyme activities, mitochondrial DNA content, and the number and size of mitochondria. Furthermore, nebula interacts with the ADP/ATP translocator and influences its activity. These results identify nebula/DSCR1 as a regulator of mitochondrial function and integrity and further suggest that an increased level of DSCR1 may contribute to the mitochondrial dysfunction seen in Down syndrome. C1 Natl Inst Neurol Disorders & Stroke, Neurogenet Branch, NIH, Bethesda, MD 20892 USA. RP Min, KT (reprint author), Natl Inst Neurol Disorders & Stroke, Neurogenet Branch, NIH, Bethesda, MD 20892 USA. EM mink@mail.nih.gov OI min, kyung-tai/0000-0003-0983-4258 FU Intramural NIH HHS NR 50 TC 49 Z9 52 U1 0 U2 11 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD NOV PY 2005 VL 8 IS 11 BP 1577 EP 1585 DI 10.1038/nn1564 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 979TB UT WOS:000232966600033 PM 16222229 ER PT J AU Ludwig, JA Weinstein, JN AF Ludwig, JA Weinstein, JN TI Biomarkers in cancer staging, prognosis and treatment selection SO NATURE REVIEWS CANCER LA English DT Review ID CELL LUNG-CANCER; GENE-EXPRESSION PROFILES; CIRCULATING TUMOR-CELLS; HISTONE DEACETYLASE INHIBITORS; COMPUTER-AIDED DETECTION; HUMAN PROSTATE-CANCER; HUMAN BREAST-CANCER; BARR-VIRUS DNA; PROMOTER METHYLATION; MOLECULAR CLASSIFICATION AB Advances in genomics, proteomics and molecular pathology have generated many candidate biomarkers with potential clinical value. Their use for cancer staging and personalization of therapy at the time of diagnosis could improve patient care. However, translation from bench to bedside outside of the research setting has proved more difficult than might have been expected. Understanding how and when biomarkers can be integrated into clinical care is crucial if we want to translate the promise into reality. C1 NCI, Genom & Bioinformat Grp, Mol Pharmacol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Weinstein, JN (reprint author), NCI, Genom & Bioinformat Grp, Mol Pharmacol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. EM weinstein@dtpax2.ncifcrf.gov RI Tang, Amy/L-3226-2016 OI Tang, Amy/0000-0002-5772-2878 FU Intramural NIH HHS NR 145 TC 763 Z9 789 U1 23 U2 261 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-175X J9 NAT REV CANCER JI Nat. Rev. Cancer PD NOV PY 2005 VL 5 IS 11 BP 845 EP 856 DI 10.1038/nrc1739 PG 12 WC Oncology SC Oncology GA 979WZ UT WOS:000232977000009 PM 16239904 ER PT J AU Fauci, AS Mavilio, D Kottilil, S AF Fauci, AS Mavilio, D Kottilil, S TI NK cells in HIV infection: Paradigm for protection or targets for ambush SO NATURE REVIEWS IMMUNOLOGY LA English DT Review ID NATURAL-KILLER-CELLS; DEPENDENT CELLULAR CYTOTOXICITY; ACQUIRED-IMMUNODEFICIENCY-SYNDROME; ACTIVE ANTIRETROVIRAL THERAPY; CLASS-I MOLECULES; INTRAVASCULAR DRUG-USERS; BLOOD MONONUCLEAR-CELLS; DENDRITIC CELLS; PERIPHERAL-BLOOD; VIRUS-INFECTION AB Natural killer cells are a crucial component of the innate immune response to certain tumours and to various viruses, fungi, parasites and bacteria. HIV has infected more than 60 million people worldwide and has led to more than 23 million deaths. At present, there are similar to 40 million people who are living with HIV infection, and there were 5 million new infections in 2004. As part of the innate immune system, natural killer cells might have an important role in host defence against HIV infection, as well as in the control of HIV replication in vivo. In this regard, it is important to understand how natural killer cells and HIV interact. This Review focuses on the role of natural killer cells in controlling HIV infection and on the impact of HIV and HIV-viraemia-induced immune activation on natural-killer-cell function. C1 NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Fauci, AS (reprint author), NIAID, Immunoregulat Lab, NIH, Bldg 31,Room 7A04,31 Ctr Dr,MSC 2520, Bethesda, MD 20892 USA. EM afauci@niaid.nih.gov OI Mavilio, Domenico/0000-0001-6147-0952 NR 99 TC 187 Z9 191 U1 0 U2 14 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1733 J9 NAT REV IMMUNOL JI Nat. Rev. Immunol. PD NOV PY 2005 VL 5 IS 11 BP 835 EP + DI 10.1038/nri1711 PG 10 WC Immunology SC Immunology GA 979TC UT WOS:000232966700008 PM 16239902 ER PT J AU Amoils, S AF Amoils, S TI Packing the punch into BCG SO NATURE REVIEWS MICROBIOLOGY LA English DT Editorial Material C1 Univ Zurich Hosp, CH-8091 Zurich, Switzerland. Yale Univ, Sch Med, New Haven, CT 06520 USA. Albert Einstein Coll Med, Bronx, NY USA. Albert Einstein Coll Med, Baltimore, MD USA. Univ Maryland, Biotechnol Inst, Baltimore, MD USA. Stanford Univ, Sch Med, Stanford, CA USA. Univ Dublin Trinity Coll, Dublin 2, Ireland. Univ Oxford, Oxford, England. Univ Aberdeen, Aberdeen, Scotland. Univ Marburg, Marburg, Germany. NIAID, NIH, Bethesda, MD USA. Astrazeneca, Chester, Cheshire, England. Univ Penn, Philadelphia, PA USA. Inst Pasteur, Paris, France. Univ Tokyo, Tokyo, Japan. UCL, London, England. RP Amoils, S (reprint author), Univ Zurich Hosp, CH-8091 Zurich, Switzerland. NR 1 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1740-1526 J9 NAT REV MICROBIOL JI Nat. Rev. Microbiol. PD NOV PY 2005 VL 3 IS 11 BP 827 EP 827 DI 10.1038/nrmicro1301 PG 1 WC Microbiology SC Microbiology GA 979GK UT WOS:000232930200002 ER PT J AU Byeon, IJL Li, HY Song, HY Gronenborn, AM Tsai, MD AF Byeon, IJL Li, HY Song, HY Gronenborn, AM Tsai, MD TI Sequential phosphorylation and multisite interactions characterize specific target recognition by the FHA domain of Ki67 SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Article ID FORKHEAD-ASSOCIATED DOMAIN; CELL-PROLIFERATION; KI-67 PROTEIN; CHECKPOINT PROTEIN; STRUCTURAL BASIS; ANTIBODY KI-67; YEAST RAD53; NMR; ANTIGEN; BINDING AB The forkhead-associated (FHA) domain of human Ki67 interacts with the human nucleolar protein hNIFK, recognizing a 44-residue fragment, hNIFK(226-269), phosphorylated at Thr234. Here we show that high-affinity binding requires sequential phosphorylation by two kinases, CDK1 and GSK3, yielding pThr238, pThr234 and pSer230. We have determined the solution structure of Ki67FHA in complex with the triply phosphorylated peptide hNIFK(226-269)3P, revealing not only local recognition of pThr234 but also the extension of the beta-sheet of the FHA domain by the addition of a beta-strand of hNIFK. The structure of an FHA domain in complex with a biologically relevant binding partner provides insights into ligand specificity and potentially links the cancer marker protein Ki67 to a signaling pathway associated with cell fate specification. C1 NIDDKD, Chem Phys Lab, US NIH, Bethesda, MD 20892 USA. Ohio State Univ, Dept Chem, Columbus, OH 43210 USA. Ohio State Univ, Dept Biochem, Columbus, OH 43210 USA. Ohio State Univ, Ohio State Biochem Program, Columbus, OH 43210 USA. Univ Pittsburgh, Sch Med, Program Struct Biol, Pittsburgh, PA 15261 USA. Acad Sinica, Genom Res Ctr, Taipei 115, Taiwan. RP Gronenborn, AM (reprint author), NIDDKD, Chem Phys Lab, US NIH, Bethesda, MD 20892 USA. EM amg100@pitt.edu; tsai.7@osu.edu OI Tsai, Ming-Daw/0000-0003-1374-0414; Gronenborn, Angela M/0000-0001-9072-3525 FU Intramural NIH HHS; NCI NIH HHS [CA69472, CA87031] NR 43 TC 43 Z9 46 U1 0 U2 7 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1545-9985 J9 NAT STRUCT MOL BIOL JI Nat. Struct. Mol. Biol. PD NOV PY 2005 VL 12 IS 11 BP 987 EP 993 DI 10.1038/nsmb1008 PG 7 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 981VC UT WOS:000233115100012 PM 16244663 ER PT J AU Kobayashi, H Kawamoto, S Brechbiel, MW Bernardo, M Sato, N Waldmann, TA Tagaya, Y Choyke, PL AF Kobayashi, H Kawamoto, S Brechbiel, MW Bernardo, M Sato, N Waldmann, TA Tagaya, Y Choyke, PL TI Detection of lymph node involvement in hematologic malignancies using micromagnetic resonance lymphangiography with a gadolinum-labeled dendrimer nanoparticle SO NEOPLASIA LA English DT Article DE malignant lymphoma; MRI; lymph node; lymphatic flow; nanoparticle ID CONTRAST AGENT; BREAST-CANCER; LYMPHOGRAPHY; MICE; MRI; LYMPHOSCINTIGRAPHY; METASTASES AB Animal models of lymphoma should reflect their counterparts in humans; however, it can be difficult to ascertain whether an induced disease is intralymphatic or extralymphatic based on direct visualization. Current imaging methods are insufficient for identifying lymphatic and intralymphatic involvement. To differentiate intralymphatic from extralymphatic involvement, we have developed a magnetic resonance imaging-based lymphangiography method and tested it on two animal models of lymphoma. A gadolinium (Gd)-labeled dendrimer nanoparticle (generation-6; similar to 220 kDa/similar to 10 nm) was injected interstitially into mice bearing hematologic malignancies to perform dynamic micromagnetic resonance lymphangiography (micro-MRIL). Both a standard T1-weighted 3D fast spoiled gradient echo and a T2/T1-weighted D-fast imaging employing steady-state acquisition (3D-FIESTA-C) were compared in an imaging study to differentiate intralymphatic from extralymphatic involvement of tumors. The lymphatics and lymph nodes were visualized with both methods in all cases. In addition, 3D-FIESTA-C depicted both the lymphatic system and the extralymphatic tumor. In an animal model, 3D-FIESTA-C demonstrated that the bulk of the tumor thought to be intralymphatic was actually extralymphatic. In conclusion, micro-MRL, using Gd-labeled dendrimer nanoparticles with the combined method, can define both the normal and abnormal lymphatics and can distinguish intralymphatic from extralymphatic diseases in mouse models of malignant lymphoma. C1 NCI, Mol Imaging Program, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Radiol, Baltimore, MD 21218 USA. NCI, Radiat Oncol Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. NCI, Mol Imaging Program, Canc Res Ctr, SAIC Frederick,NIH, Frederick, MD 21701 USA. NCI, Metab Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Kobayashi, H (reprint author), NCI, Mol Imaging Program, Canc Res Ctr, NIH, Bldg 10,Room 1 B40,MSC1088,10 Ctr Dr, Bethesda, MD 20892 USA. EM kobayashi@mail.nih.gov NR 31 TC 38 Z9 41 U1 0 U2 5 PU B C DECKER INC PI HAMILTON PA 20 HUGHSON ST SOUTH, PO BOX 620, L C D 1, HAMILTON, ONTARIO L8N 3K7, CANADA SN 1522-8002 J9 NEOPLASIA JI Neoplasia PD NOV PY 2005 VL 7 IS 11 BP 984 EP 991 DI 10.1593/neo.05454 PG 8 WC Oncology SC Oncology GA 994HC UT WOS:000234020800003 PM 16331884 ER PT J AU Lahiri, DK Ge, YW Maloney, B Wavrant-De Vrieze, F Hardy, J AF Lahiri, DK Ge, YW Maloney, B Wavrant-De Vrieze, F Hardy, J TI Characterization of two APP gene promoter polymorphisms that appear to influence risk of late-onset Alzheimer's disease SO NEUROBIOLOGY OF AGING LA English DT Article DE aging; amyloid beta protein; brain; CAT reporter gene; DNA-protein interaction; E12/E47; E47; gel shift assay; polymorphism; PuF; regulatory region; transcription factor ID AMYLOID PRECURSOR PROTEIN; CELL-LINES; DIFFERENTIAL EXPRESSION; MUTATIONAL ANALYSIS; BIPOLAR DISORDER; MESSENGER-RNAS; DOWNS-SYNDROME; IDENTIFICATION; TRANSCRIPTION; REGION AB Alzheimer's disease (AD) is characterized by formation of plaques of amyloid P peptide (A beta). Autosomally-inherited or "familial" AD had been demonstrated only in connection with coding sequence mutations. We characterized DNA-protein interaction and expression influence of two polymorphisms that occur in the promoter (C <->. T at -3829 and T <-> C at - 1023, +1 transcription start site) of the A beta precursor protein (APP) gene. We report distinct functional differences in reporter expression and in DNA-protein interaction for variant sequences in both -3829 and - 1023 polymorphic regions. The -3829T variant has reduced DNA-protein interaction and reporter expression compared to -3829C, while -1023C has greater DNA-protein interaction and reporter expression than -1023T. Our predictions for likely transcription factors for loss of function (-3829T) are ADR1, MIG1, and PuF, and for gain of function (-1023C) are E12/E47, ITF-2, and RFX2. Characterization of the activity of a regulatory polymorphism of the APP gene points towards understanding mechanisms that likely underlie the majority of AD cases and may contribute to promoter-based drug design. (c) 2004 Elsevier Inc. All rights reserved. C1 Indiana Univ, Sch Med, Dept Psychiat, Inst Psychiat Res, Indianapolis, IN 46202 USA. Indiana Univ, Sch Med, Dept Mol & Med Genet, Inst Psychiat Res, Indianapolis, IN 46202 USA. NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. RP Lahiri, DK (reprint author), Indiana Univ, Sch Med, Dept Psychiat, Inst Psychiat Res, 791 N Union Dr, Indianapolis, IN 46202 USA. EM dlahiri@iupui.edu RI Hardy, John/C-2451-2009; Maloney, Bryan/C-4924-2011 OI Maloney, Bryan/0000-0003-2364-9649 FU NIA NIH HHS [AG18379, AG18884] NR 62 TC 34 Z9 35 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD NOV-DEC PY 2005 VL 26 IS 10 BP 1329 EP 1341 DI 10.1016/j.neurobiolaging.2004.11.005 PG 13 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 981DX UT WOS:000233068700001 PM 16243604 ER PT J AU Nakagawa, T Yabe, T Schwartz, JP AF Nakagawa, T Yabe, T Schwartz, JP TI Gene expression profiles of reactive astrocytes cultured from dopamine-depleted striatum SO NEUROBIOLOGY OF DISEASE LA English DT Article DE astrocyte; reactive; gene array; Parkinson's disease ID ENDOTHELIAL GROWTH-FACTOR; NF-KAPPA-B; PARKINSONS-DISEASE; CELL-DENSITY; ENHANCED SURVIVAL; ASTROGLIAL CELLS; TROPHIC ACTIVITY; CARCINOMA-CELLS; MESSENGER-RNA; NEURONS AB We have carried out cDNA array analysis in order to characterize the gene expression profiles of reactive astrocytes from dopamine-depleted striation. Astrocytes were cultured from the striation of normal adult rats (adult astrocytes) or adult rats in which the substantia nigra had been lesioned I week earlier with 6-hydroxydopamine (reactive astrocytes), an animal model for Parkinson's disease. Three antibodies, 19D1, O1E4, and 13A11, known to label only reactive astrocytes in vivo, stained cultured reactive astrocytes but not adult astrocytes. Analysis with cDNA arrays showed that 38 genes were up-regulated and 75 genes down-regulated in reactive astrocytes compared to normal adult astrocytes. The expression of growth factor and transcription factor genes predominated among the up-regulated genes while those for signal transduction molecules, metabolic enzymes, and receptors for growth factors, hormones, and neurotransmitters predominated among the down-regulated genes. These results will allow the field to address the molecular profiles and functions of astrocytes activated in response to dopamine depletion and may be useful for developing new therapies for Parkinson's disease. Published by Elsevier Inc. C1 NINDS, Neurotrop Factors Sect, NIH, DHHS, Bethesda, MD 20892 USA. RP Schwartz, JP (reprint author), NINDS, Neurotrop Factors Sect, NIH, DHHS, Bldg,1Room 135, Bethesda, MD 20892 USA. EM jps@helix.nih.gov NR 34 TC 10 Z9 11 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 0969-9961 J9 NEUROBIOL DIS JI Neurobiol. Dis. PD NOV PY 2005 VL 20 IS 2 BP 275 EP 282 DI 10.1016/j.nbd.2005.03.009 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 981OA UT WOS:000233096700011 PM 16242635 ER PT J AU Liang, ZQ Wang, XX Wang, YM Chuang, DM DiFiglia, M Chase, TN Qin, ZH AF Liang, ZQ Wang, XX Wang, YM Chuang, DM DiFiglia, M Chase, TN Qin, ZH TI Susceptibility of striatal neurons to excitotoxic injury correlates with basal levels of Bcl-2 and the induction of P53 and c-Myc immunoreactivity SO NEUROBIOLOGY OF DISEASE LA English DT Article DE Huntington's disease; excitotoxicity; striatum; apoptosis; neurodegeneration; cholinergic interneurons ID D-ASPARTATE RECEPTORS; KAPPA-B ACTIVATION; HUNTINGTONS-DISEASE GENE; INDUCED CELL-DEATH; QUINOLINIC ACID; RAT STRIATUM; MEDIATED EXCITOTOXICITY; TRANSGENIC MICE; MESSENGER-RNA; CASPASE-3-LIKE PROTEASE AB The present studies evaluated the potential contribution of Bcl-2, p53, and c-Myc to the differential vulnerability of striatal neurons to the excitotoxin quinolinic acid (QA). In normal rat striatum, Bcl-2 immunoreactivity (Bcl-2-i) was most intense in large aspiny interneurons including choline acetyltransferase positive (CAT(+)) and parvalbumin positive (PARV(+)) neurons, but low in a majority of medium-sized neurons. In human brain, intense Bcl-2-i was seen in large striatal neurons but not in medium-sized spiny projection neurons. QA produced degeneration of numerous medium-sized neurons, but not those enriched in Bcl-2-i. Many Bcl-2-i-enriched interneurons including those with CAT(+) and PARV(+) survived QA injection, while medium-sized neurons labeled for calbindin D-28K (CAL D-28(+)) did not. In addition, proapoptotic proteins p53-i and c-Myc-i were robustly induced in medium-sized neurons, but not in most large neurons. The selective vulnerability of striatal medium spiny neurons to degeneration in a rodent model of Huntington's disease appears to correlate with their low levels of Bcl-2-i and high levels of induced p53-i and c-Myc-i. (c) 2005 Elsevier Inc. All rights reserved. C1 Soochow Univ, Sch Med, Dept Pharmacol, Suzhou 215007, Peoples R China. NINDS, Expt Therapeut Branch, NIH, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Lab Cellular Neurobiol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. NIMH, Mol Neurobiol Sect, NIH, Bethesda, MD 20892 USA. RP Qin, ZH (reprint author), Soochow Univ, Sch Med, Dept Pharmacol, 48 Ren Min Rd, Suzhou 215007, Peoples R China. EM qinzh555@peoplepc.com NR 84 TC 18 Z9 18 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0969-9961 J9 NEUROBIOL DIS JI Neurobiol. Dis. PD NOV PY 2005 VL 20 IS 2 BP 562 EP 573 DI 10.1016/j.nbd.2005.04.011 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 981OA UT WOS:000233096700039 PM 15922606 ER PT J AU Xu, S Yang, JH Ll, CQ Zhu, WJ Shen, J AF Xu, S Yang, JH Ll, CQ Zhu, WJ Shen, J TI Metabolic alterations in focally activated primary somatosensory cortex of alpha-chloralose-anesthetized rats measured by H-1 MRS at 11.7 T SO NEUROIMAGE LA English DT Article DE phosphocreatine; lactate; focal activation; forepaw stimulation ID HUMAN VISUAL-CORTEX; MAGNETIC-RESONANCE-SPECTROSCOPY; CEREBRAL-BLOOD-FLOW; VIVO C-13 NMR; HUMAN BRAIN; FOREPAW STIMULATION; GLUCOSE CONSUMPTION; PHOTIC-STIMULATION; ENERGY-METABOLISM; P-31-MR SPECTROSCOPY AB Previously, magnetic resonance spectroscopy studies of alterations in cerebral metabolite concentration during functional activation have been focused on phosphocreatine using (31)p MRS and lactate using H-1 MRS with controversial results. Recently, significant improvements on the spectral resolution and sensitivity of in vivo spectroscopy have been made at ultrahigh magnetic field strength. Using highly resolved localized short-TE H-1 MRS at 11.7 T, we report metabolic responses of rat somatosensory cortex to forepaw stimulation in alpha-chloralose-anesthetized rats. The phosphocreatine/creatine ratio was found to be significantly decreased by 15.1 +/- 4.6% (mean +/- SEM, P < 0.01). Lactate remained very low (similar to<0.3 mu mol/g w/w) with no statistically significant changes observed during forepaw stimulation at a temporal resolution of 10.7 min. An increase in glutamine and a decrease in glutamate and myo-inositol were also detected in the stimulated state. Our results suggest that, under the experimental conditions used in this study, increased energy consumption due to focal activation causes a shift in the creatine kinase reaction towards the direction of adenosine triphosphate production. At the same time, metabolic matching prevails during increased energy consumption with no significant increase in the glycolytic product lactate in the focally activated primary somatosensory cortex of alpha-chloralose-anesthetized rats. Published by Elsevier Inc. C1 NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA. RP Shen, J (reprint author), NIMH, Mol Imaging Branch, Bldg 10,Room 2D51A,9000 Rockville Pike, Bethesda, MD 20892 USA. EM shenj@intra.nimh.nih.gov NR 54 TC 35 Z9 36 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD NOV 1 PY 2005 VL 28 IS 2 BP 401 EP 409 DI 10.1016/j.neuroimage.2005.06.016 PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 977QB UT WOS:000232817200010 PM 16182571 ER PT J AU Kim, DK Tolliver, TJ Huang, SJ Martin, BJ Andrews, AM Wichems, C Holmes, A Lesch, KP Murphy, DL AF Kim, DK Tolliver, TJ Huang, SJ Martin, BJ Andrews, AM Wichems, C Holmes, A Lesch, KP Murphy, DL TI Altered serotonin synthesis, turnover and dynamic regulation in multiple brain regions of mice lacking the serotonin transporter SO NEUROPHARMACOLOGY LA English DT Article DE serotonin transporter; synthesis; homeostasis; tryptophan hydroxylase; gender; knockout mouse ID AUTORECEPTOR-MEDIATED INHIBITION; TYROSINE-HYDROXYLASE ACTIVITY; HUMAN TRYPTOPHAN-HYDROXYLASE; AMINO-ACID DECARBOXYLASE; KNOCK-OUT MICE; 5-HT TRANSPORTER; IN-VIVO; ANTIDEPRESSANT DRUGS; DORSAL RAPHE; MONOAMINE TRANSPORTERS AB To evaluate the consequences of inactivation of the serotonin transporter (SERT) gene on 5-HT homeostasis and function, 5-HT synthesis and turnover rates were measured using the decarboxylase inhibition method in multiple brain regions (frontal cortex, striatum, brainstem, hippocampus and hypothalamus) from mice with a genetic disruption of SERT. 5-HT synthesis rates were increased 30-60% in the different brain regions of SERT -/- mice compared to littermate +/+ control mice despite 55-70% reductions in tissue 5-HT concentrations. Brain regions that possessed a greater capacity to increase synthesis and turnover (frontal cortex, striatum) demonstrated lesser reductions in tissue 5-HT. Female SERT -/- mice had greater increases (79%) in brain 5-HT synthesis than male -/- mice did (25%), a finding associated with higher brain tryptophan concentrations in females. Despite increased 5-HT synthesis, there was no change in either TPH2 or TPH1 mRNA levels or in maximal in vitro TPH activity in the brainstem of SERT -/- mice. Catecholamine homeostasis as reflected in brain tissue concentrations and in synthesis and turnover of dopamine and norepinephrine was unchanged in SERT -/- mice. Taken together, the results demonstrate a markedly altered homeostatic situation in SERT -/- mice that lack 5-HT reuptake, resulting in markedly depleted tissue stores that are inadequately compensated for by increased 5-HT synthesis, with brain region and gender specificity observed. Published by Elsevier Ltd. C1 NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA. Penn State Univ, Dept Vet Sci, University Pk, PA 16802 USA. Penn State Univ, Huck Inst Life Sci, University Pk, PA 16802 USA. Pfizer Inc, Cremorne, NSW, Australia. NIAAA, Lab Integrat Neurosci, Sect Behav Sci & Genet, NIH, Bethesda, MD 20892 USA. Univ Wurzburg, Dept Psychiat & Psychotherapy, Wurzburg, Germany. RP Murphy, DL (reprint author), NIMH, Clin Sci Lab, NIH, Bldg 10,Room 3D41, Bethesda, MD 20892 USA. EM dennismurphy@mail.nih.gov RI Andrews, Anne/B-4442-2011; Lesch, Klaus-Peter/J-4906-2013 OI Andrews, Anne/0000-0002-1961-4833; Lesch, Klaus-Peter/0000-0001-8348-153X FU Intramural NIH HHS NR 71 TC 107 Z9 111 U1 4 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD NOV PY 2005 VL 49 IS 6 BP 798 EP 810 DI 10.1016/j.neuropharm.2005.08.010 PG 13 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 983FW UT WOS:000233217700009 PM 16183083 ER PT J AU Esslinger, CS Agarwal, S Gerdes, J Wilson, PA Davis, ES Awes, AN O'Brien, E Mavencamp, T Koch, HP Poulsen, DJ Rhoderick, JF Chamberlin, AR Kavanaugh, MP Bridges, RJ AF Esslinger, CS Agarwal, S Gerdes, J Wilson, PA Davis, ES Awes, AN O'Brien, E Mavencamp, T Koch, HP Poulsen, DJ Rhoderick, JF Chamberlin, AR Kavanaugh, MP Bridges, RJ TI The substituted aspartate analogue L-beta-threo-benzyl-aspartate preferentially inhibits the neuronal excitatory amino acid transporter EAAT3 SO NEUROPHARMACOLOGY LA English DT Article DE glutamate uptake; transport inhibitors; pharmacophore model; neurotransmitter transporter; molecular modeling ID POSTTRANSCRIPTIONAL REGULATORY ELEMENT; CENTRAL-NERVOUS-SYSTEM; GLUTAMATE TRANSPORTERS; HIGH-AFFINITY; RAT-BRAIN; NONSUBSTRATE INHIBITOR; EXPRESSION; SUBTYPES; SUBSTRATE; SODIUM AB The excitatory amino acid transporters (EAATs) play key roles in the regulation of CNS L-glutamate, especially related to synthesis, signal termination, synaptic spillover, and excitotoxic protection. Inhibitors available to delineate EAAT pharmacology and function are essentially limited to those that non-selectively block all EAATs or those that exhibit a substantial preference for EAAT2. Thus, it is difficult to selectively study the other subtypes, particularly EAAT1 and EAAT3. Structure activity studies on a series of beta-substituted aspartate analogues identify L-beta-benzyl-aspartate (L-beta-BA) as among the first blockers that potently and preferentially inhibits the neuronal EAAT3 subtype. Kinetic analysis of D-[H-3]aspartate uptake into C17.2 cells expressing the hEAATs demonstrate that L-beta-threo-BA is the more potent diastereomer, acts competitively, and exhibits a 10-fold preference for EAAT3 compared to EAAT1 and EAAT2. Electrophysiological recordings of EAAT-mediated currents in Xenopus oocytes identify L-beta-BA as a non-substrate inhibitor. Analyzing L-beta-threo-BA within the context of a novel EAAT2 pharmacophore model suggests: (1) a highly conserved positioning of the electrostatic carboxyl and amino groups; (2) nearby regions that accommodate select structural modifications (cyclopropyl rings, methyl groups, oxygen atoms); and (3) a unique region L-beta-threo-BA occupied by the benzyl moieties Of L-TBOA, L-beta-threo-BA and related analogues. It is plausible that the preference Of L-beta-threo-BA and L-TBOA for EAAT3 and EAAT2, respectively, could reside in the latter two pharmacophore regions. (c) 2005 Elsevier Ltd. All rights reserved. C1 Univ Montana, COBRE, Ctr Struct & Funct Neurosci, Dept Biomed Sci, Missoula, MT 59812 USA. Univ Montana, COBRE, Ctr Struct & Funct Neurosci, Dept Pharmaceut Sci, Missoula, MT 59812 USA. Univ Montana, COBRE, Ctr Struct & Funct Neurosci, Dept Chem, Missoula, MT 59812 USA. Univ Calif Irvine, Dept Chem, Irvine, CA 92627 USA. RP Bridges, RJ (reprint author), Univ Montana, COBRE, Ctr Struct & Funct Neurosci, Dept Biomed Sci, Missoula, MT 59812 USA. EM richard.bridges@umontana.edu FU NCRR NIH HHS [RR15583]; NINDS NIH HHS [R01 NS027600, NS1R13536405, NS33270, NS30570, NS27600] NR 51 TC 37 Z9 39 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD NOV PY 2005 VL 49 IS 6 BP 850 EP 861 DI 10.1016/j.neuropharm.2005.08.009 PG 12 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 983FW UT WOS:000233217700014 PM 16183084 ER PT J AU Greenwood, PM Sunderland, T Putnam, K Levy, J Parasuraman, R AF Greenwood, PM Sunderland, T Putnam, K Levy, J Parasuraman, R TI Scaling of visuospatial attention undergoes differential longitudinal change as a function of APOE genotype prior to old age: Results from the NIMH BIOCARD study SO NEUROPSYCHOLOGY LA English DT Article DE Alzheimer's; APOE; longitudinal; visual search ID APOLIPOPROTEIN-E EPSILON-4; POSITRON-EMISSION-TOMOGRAPHY; POSTERIOR PARIETAL CORTEX; EVENT-RELATED POTENTIALS; ALZHEIMERS-DISEASE; COGNITIVE DECLINE; SPATIAL ATTENTION; VISUAL-SEARCH; NEUROFIBRILLARY CHANGES; ELDERLY INDIVIDUALS AB The effect of apolipoprotein E (APOE) genotype on longitudinal cognitive decline in midlife was investigated with attentional scaling. Healthy individuals (mean age 59.6 years) genotyped for APOE were tested at 3 12-month intervals on a cued visual search task. A random effects model revealed significant interaction in effect of precue size on search speed between APOE-epsilon 4 gene dose and assessment, with longitudinal increases in noncarriers and heterozygotes but longitudinal decreases, in homozygotes. Association of APOE-epsilon 4 with cognitive decline in midlife is consistent with an Alzheimer's disease (AD) prodrome, albeit a decade or more before average age of AD diagnosis. However, cognitive decline in midlife associated with a gene modulating neuronal response to insult argues that the concept of all AD prodrome includes factors that allow as well as cause AD. C1 Catholic Univ Amer, Cognit Sci Lab, Washington, DC 20064 USA. NIMH, Geriatr Psychiat Branch, Bethesda, MD 20892 USA. RP Greenwood, PM (reprint author), George Mason Univ, Dept Psychol, MS 3F5,4400 Univ Dr, Fairfax, VA 22030 USA. EM pgreenw1@gmu.edu FU NIA NIH HHS [AG19653, AG07569, AG12387] NR 75 TC 25 Z9 26 U1 0 U2 3 PU AMER PSYCHOLOGICAL ASSOC/EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0894-4105 J9 NEUROPSYCHOLOGY JI Neuropsychology PD NOV PY 2005 VL 19 IS 6 BP 830 EP 840 DI 10.1037/0894-4105.19.6.830 PG 11 WC Psychology, Clinical; Neurosciences; Psychology SC Psychology; Neurosciences & Neurology GA 993TJ UT WOS:000233977700013 PM 16351359 ER PT J AU Rao, JS Rapoport, SI Bosetti, F AF Rao, JS Rapoport, SI Bosetti, F TI Decrease in the AP-2 DNA-binding activity and in the protein expression of AP-2 alpha and AP-2 beta in frontal cortex of rats treated with lithium for 6 weeks SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE brain; lithium; transcription factors; PKC; AP-2; AP-1 ID SIGNAL-TRANSDUCTION PATHWAYS; CYTOSOLIC PHOSPHOLIPASE A(2); BIPOLAR AFFECTIVE-DISORDER; TRANSCRIPTION FACTOR AP-2; KINASE-C ACTIVITY; GENE-EXPRESSION; ARACHIDONIC-ACID; CEREBRAL-CORTEX; CYCLIC-AMP; NEUROTROPHIC FACTOR AB Lithium chloride (LiCl), when fed to rats for 6 weeks, has been reported to decrease brain mRNA, protein, and activity levels of arachidonic acid (AA)-selective cytosolic phospholipase A(2) (cPLA(2)), without affecting secretory sPLA(2) or Ca2+-independent iPLA(2) We investigated whether transcription factors known to regulate cPLA(2) gene expression are modulated by chronic lithium treatment. Male Fischer-344 rats were fed a LiCl-containing diet for 6 weeks to produce a therapeutically relevant brain lithium concentration. Control animals were fed a LiCl-free diet. Using a gelshift assay, we found that LiCl significantly decreased activating protein 2 (AP-2)-binding activity, and protein levels of the AP-2 alpha and AP-2 beta but not of the AP-2 gamma subunits in the frontal cortex. Activating protein 1 (AP- 1)binding activity was increased, whereas glucocorticoid response element, polyoma enhancer activator 3, and nuclear factor kappa B DNA-binding activities were not changed significantly, Since both cPLA(2) and AP-2 can be activated by protein kinase C (PKC), we examined the frontal cortex protein levels of PKC alpha and PKC epsilon, as well as AA-dependent PKC activity. The protein levels of PKC alpha and PKC e were decreased significantly, as was AA-dependent PKC activity, in the lithium-treated compared to control rats, Our results suggest that the reported decrease in brain gene expression of cPLA(2) by chronic lithium may be mediated by reduced AP-2 transcriptional activity, and that decreased expression of PKC a and PKC e. contributes to lowering the AP-2 activity. C1 NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. RP Rao, JS (reprint author), NIA, Brain Physiol & Metab Sect, NIH, 9000 Rockville Pike,Bldg 9,IS 128, Bethesda, MD 20892 USA. EM jrao@mail.nih.gov RI Rao, Jagadeesh/C-1250-2009 NR 61 TC 36 Z9 36 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD NOV PY 2005 VL 30 IS 11 BP 2006 EP 2013 DI 10.1038/sj.npp.1300740 PG 8 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 977EJ UT WOS:000232784900005 PM 15827566 ER PT J AU Solinas, M Goldberg, SR AF Solinas, M Goldberg, SR TI Motivational effects of cannabinoids and opioids on food reinforcement depend on simultaneous activation of cannabinoid and opioid systems SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE cannabis; opiates; progressive ratio; appetite; anorexigenic; obesity ID RECEPTOR KNOCKOUT MICE; PROGRESSIVE RATIO SCHEDULES; NUCLEUS-ACCUMBENS; 2-ARACHIDONOYL GLYCEROL; ANTAGONIST SR-141716; DOPAMINE RELEASE; SEEKING BEHAVIOR; BETA-ENDORPHIN; CB1 RECEPTORS; MORPHINE AB Strong functional interactions exist between endogenous cannabinoid and opioid systems. Here, we investigated whether cannabinoid-opioid interactions modulate motivational effects of food reinforcement. In rats responding for food under a progressive-ratio schedule, the maximal effort (break point) expended to obtain 45 mg pellets depended on the level of food deprivation, with free-feeding reducing break points and food-deprivation increasing break points. Delta-9-tetrahydrocannabinol (THC; 0.3-5.6 mg/kg intrapeitoneally (i.p.)) and morphine (1-10 mg/kg i.p.) dose-dependently increased break points for food reinforcement, while the cannabinoid CB I receptor antagonist rimonabant (SR-1417 1 6A; 0.3-3 mg/kg i.p.) and the preferential mu-opioid receptor antagonist naloxone (0.3-3 mg/kg i.p.) dose-dependently decreased break points. THC and morphine only increased break points when food was delivered during testing, suggesting that these treatments directly influenced reinforcing effects of food, rather than increasing behavior in a nonspecific manner. Effects of THC were blocked by rimonabant and effects of morphine were blocked by naloxone, demonstrating that THC's effects depended on cannabinoid CB I receptor activation and morphine's effects depended on opioid-receptor activation. Furthermore, THC's effects were blocked by naloxone and morphine's effects were blocked by rimonabant, demonstrating that mu-opioid receptors were involved in the effects of THC and cannabinoid CB I receptors were involved in the effects of morphine on food-reinforced behavior. Thus, activation of both endogenous cannabinoid and opioid systems appears to jointly facilitate motivational effects of food measured under progressive-ratio schedules of reinforcement and this facilitatory modulation appears to critically depend on interactions between these two systems. These findings support the proposed therapeutic utility of cannabinoid agonists and antagonists in eating disorders. C1 NIDA, Preclin Pharmacol Sect, Behav Neurosci Branch, Intramural Res Program,NIH,Dept Hlth & Human Serv, Baltimore, MD USA. RP Solinas, M (reprint author), Univ Poitiers, CNRS 6187, Lab Biol & Physiol Cellulaires, 40 Ave Recteur Pineau, F-86022 Poitiers, France. EM msolinas@intra.nida.nih.gov RI Solinas, Marcello/M-3500-2016 OI Solinas, Marcello/0000-0002-0664-5964 FU Intramural NIH HHS NR 69 TC 92 Z9 94 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD NOV PY 2005 VL 30 IS 11 BP 2035 EP 2045 DI 10.1038/sj.npp.1300720 PG 11 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 977EJ UT WOS:000232784900008 PM 15812567 ER PT J AU Solinas, M Panlilio, LV Tanda, G Makriyannis, A Matthews, SA Goldberg, SR AF Solinas, M Panlilio, LV Tanda, G Makriyannis, A Matthews, SA Goldberg, SR TI Cannabinoid agonists but not inhibitors of endogenous cannabinoid transport or metabolism enhance the reinforcing efficacy of heroin in rats SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE heroin; THC; drug self-administration; progressive-ratio schedule; endocannabinoids; reinforcement ID RECEPTOR KNOCKOUT MICE; ACID AMIDE HYDROLASE; VENTRAL TEGMENTAL AREA; CONDITIONED PLACE PREFERENCE; ANANDAMIDE TRANSPORT; VANILLOID RECEPTORS; CB1 RECEPTOR; NUCLEUS-ACCUMBENS; SUBSTANTIA-NIGRA; DOPAMINE NEURONS AB Accumulating evidence suggests that the endogenous cannabinoid system is involved in the reinforcing effects of heroin, In rats intravenously self-administering heroin, we investigated effects of cannabinoid CB1 receptor agonists and compounds that block transport or metabolism of the endogenous cannabinoid anandamide. The natural cannnabinoid CB1 receptor agonist delta-9-tetrahydrocannabinol (THC, 0.3-3 mg/kg i.p.) did not alter self-administration of heroin under a fixed-ratio one (FRI) schedule, except at a high 3 mg/kg dose which decreased heroin self-administration, Under a progressive-ratio schedule, however, THC dose-dependently increased the number of 50 mu g/kg heroin injections self-administered per session and the maximal ratio completed (break-point), with peak increases at I mg/kg THC. In addition, 1 mg/kg THC increased break-points and injections self-administered over a wide range of heroin injection doses (25- 100 mu g/kg), indicating an increase in heroin's reinforcing efficacy and not its potency. The synthetic cannabinod CB1 receptor agonist WIN55,212-2 (0.3-3 mg/kg i.p.) had effects similar to THC under the progressive-ratio schedule. In contrast, AM-404 (1-10 mg/kg i.p.), an inhibitor of transport of anandamide, and URB-597 (0.01-03 mg/kg i.p,), an inhibitor of the enzyme fatty acid amide hydrolase (FAAH) that degrades anandamide, or their combination, did not increase reinforcing efficacy of heroin at any dose tested. Thus, activation of cannabinoid CB1 receptors facilitates the reinforcing efficacy of heroin and this appears to be mediated by interactions between cannabinoid CB1 receptors and mu-opioid receptors and their signaling pathways, rather than by an opioid-induced release of endogenous cannabinoids. C1 NIDA, Preclin Pharmacol Sect, Behav Neurosci Branch,Intramural Res Program, NIH,Dept Hlth & Human Serv, Baltimore, MD USA. Univ Poitiers, CNRS 6187, Lab Biol & Physiol Cellulaires, Poitiers, France. NIDA, Psychobiol Sect, Med Discovery Res Branch,Intramural Res Program, NIH,Dept Hlth & Human Serv, Baltimore, MD USA. Northeastern Univ, Ctr Drug Discovery, Boston, MA 02115 USA. RP Goldberg, SR (reprint author), NIDA, Preclin Pharmacol Sect, Behav Neurosci Res Branch, Div Intramural Res,NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM sgoldber@intra.nida.nih.gov RI Tanda, Gianluigi/B-3318-2009; Solinas, Marcello/M-3500-2016 OI Tanda, Gianluigi/0000-0001-9526-9878; Solinas, Marcello/0000-0002-0664-5964 FU NIDA NIH HHS [DA03801, DA09158] NR 67 TC 60 Z9 62 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD NOV PY 2005 VL 30 IS 11 BP 2046 EP 2057 DI 10.1038/sj.npp.1300754 PG 12 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 977EJ UT WOS:000232784900009 PM 15870833 ER PT J AU Cadet, JL Jayanthi, S Deng, XL AF Cadet, JL Jayanthi, S Deng, XL TI Methamphetamine-induced neuronal apoptosis involves the activation of multiple death pathways. Review. SO NEUROTOXICITY RESEARCH LA English DT Review DE methamphetamine; neuronal apoptosis; mitochondria; endoplasmic reticulum; Fas; FasL ID DISMUTASE TRANSGENIC MICE; TYROSINE-HYDROXYLASE ACTIVITY; INDUCED NEUROTOXICITY; RAT-BRAIN; ENDOPLASMIC-RETICULUM; STRIATAL DOPAMINE; FREE-RADICALS; CELL-DEATH; INTRACEREBRAL HEMORRHAGE; AMPHETAMINE ABUSE AB The abuse of the illicit drug methamphetamine (METH) is a major concern because it can cause terminal degeneration and neuronal cell death in the brain. METH-induced cell death occurs via processes that resemble apoptosis. In the present review, we discuss the role of various apoptotic events in the causation of METH-induced neuronal apoptosis in vitro and in vivo. Studies using comprehensive approaches to gene expression profiling have allowed for the identification of several genes that are up-regulated or down-regulated after an apoptosis-inducing dose of the drug. Further experiments have also documented the fact that the drug can cause demise of striatal enkephalinergic neurons by cross-talks between mitochondria-, endoplasmic reticulum- and receptor-mediated apoptotic events. These neuropathological observations have also been reported in models of drug-induced neuroplastic alterations used to mimic drug addiction (Nestler, 2001). C1 NIDA, Intramural Res Program, Dept Hlth & Human Serv, Mol Neuropsychiat Branch,NIH, Baltimore, MD 21224 USA. RP Cadet, JL (reprint author), NIDA, Intramural Res Program, Dept Hlth & Human Serv, Mol Neuropsychiat Branch,NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM JCADET@intra.nida.nih.gov FU Intramural NIH HHS NR 106 TC 57 Z9 62 U1 2 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1029-8428 J9 NEUROTOX RES JI Neurotox. Res. PD NOV PY 2005 VL 8 IS 3-4 BP 199 EP 206 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 019AV UT WOS:000235808900001 PM 16371314 ER PT J AU Dinh, B Dove, K Jappar, D Hrabie, JA Davies, KM AF Dinh, B Dove, K Jappar, D Hrabie, JA Davies, KM TI Effect of hydrophobic structure on the catalysis of nitric oxide release from zwitterionic diazeniumdiolates in surfactant and liposome media SO NITRIC OXIDE-BIOLOGY AND CHEMISTRY LA English DT Article DE nitric oxide; diazeniumdiolate; surfactant; liposome ID THROMBORESISTANT; DISSOCIATION; CHEMISTRY; MECHANISM; POLYMERS AB The effect of phospholipid liposomes and surfactant micelles on the rate of nitric oxide release from zwitterionic diazeniumdiolates, (RRN)-R-1-N-2[N(O)NO](-), with significant hydrophobic structure, has been explored. The acid-catalyzed dissociation of NO has been examined in phosphate-buffered solutions of sodium dodecylsulfate (SDS) micelles and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and 1,2-dipalmitoyl-sn-glycero-3-[phospho-(1-glycerol)] sodium salt (DPPG) phospholipid liposomes. The reaction behavior of dibenzylamine-, monobenzylamine-, and dibutylamine-derived substrates [1]: R-1 = C6H5CH2, R-2 = C6H5CH2 NH2+(CH2)(2), 2: R-1 = C6H5CH2, R-2 = NH3+(CH2)(2), and 3: R-1 = n-butyl, R-2 = n-butyl-NH2+(CH2)(6)] has been compared with that of SPER/NO, 4: R-1 = H2N(CH2) 3, R-2 = H2N(CH2) 3NH2+(CH2)(4)]. Catalysis of NO release is observed in both micellar and liposome media. Hydrophobic interactions contribute to micellar binding for 1-3 and appear to be the main factor facilitating catalysis by charge neutral DPPC liposomes. Binding constants for the association of I and 3 with SDS micelles were 3-fold larger than those previously obtained with comparable zwitterionic substrates lacking their hydrophobic structure. Anionic DPPG liposomes were much more effective in catalyzing NO release than either DPPC liposomes or SDS micelles. DPPG liposomes (at 10 mM total lipid) induced a 30-fold increase in the NO dissociation rate of SPER/NO compared to 12- and 14-fold increases in that of I and 3. (c) 2005 Elsevier Inc. All rights reserved. C1 George Mason Univ, Dept Chem & Biochem, Fairfax, VA 22030 USA. SAIC Frederick, Natl Canc Inst, Basic Res Program, Ft Detrick, MD 21702 USA. RP Davies, KM (reprint author), George Mason Univ, Dept Chem & Biochem, Fairfax, VA 22030 USA. EM kdavies@gmu.edu FU NCI NIH HHS [N01-CO-12400]; NHLBI NIH HHS [R15-HL078750-01]; NIGMS NIH HHS [R15 GM61560-01] NR 21 TC 9 Z9 10 U1 1 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1089-8603 J9 NITRIC OXIDE-BIOL CH JI Nitric Oxide-Biol. Chem. PD NOV PY 2005 VL 13 IS 3 BP 204 EP 209 DI 10.1016/j.niox.2005.07.003 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 979BO UT WOS:000232917300007 PM 16122951 ER PT J AU North, KE Almasy, L Goring, HHH Cole, SA Diego, VP Laston, S Cantu, T Williams, JT Howard, BV Lee, ET Best, LG Fabsitz, RR MacCluer, JW AF North, KE Almasy, L Goring, HHH Cole, SA Diego, VP Laston, S Cantu, T Williams, JT Howard, BV Lee, ET Best, LG Fabsitz, RR MacCluer, JW TI Linkage analysis of factors underlying insulin resistance: Strong Heart Family Study SO OBESITY RESEARCH LA English DT Article DE linkage; American Indians; insulin resistance; human chromosome 12; human chromosome 4 ID GENOME-WIDE SCAN; METABOLIC SYNDROME; AMERICAN-INDIANS; CARDIOVASCULAR-DISEASE; BLOOD-PRESSURE; RECEPTOR; PLASMA; CHOLESTEROL; PHENOTYPES; PEDIGREES AB In previous work in non-diabetic participants of the Strong Heart Family Study, we identified three heritable principal components of nine insulin resistance (IR) phenotypes: 1) a glucose/insulin/obesity factor, 2) a blood pressure factor, and 3) a dyslipidemia factor. To localize quantitative trait loci (QTL) potentially influencing these factors, we conducted a genome scan of factor scores in Strong Heart Family Study participants. Approximately 599 men and women, >= 18 years of age, in 32 extended families at three centers (in Arizona, Oklahoma, and North and South Dakota), were examined between 1997 and 1999. We used variance components linkage analysis to identify QTLs for the IR factors. With age, sex, and study center as covariates, we detected linkage of the glucose/insulin/obesity factor to chromosome 4 (robust looarithrut of the odds (LOD) = 2.2), the dyslipidemia factor to chromosome 12 (robust LOD = 2.7), and the blood pressure factor to chromosome I (robust LOD = 1.6). The peak linkage signals identified for these IR factors support several positive findings from other studies and occur in regions harboring interesting candidate genes. The corroboration of existing QTLs will bring us closer to the identification of the functional genes that predispose to IR. C1 Univ N Carolina, Dept Epidemiol, Hill Bank Amer Ctr, Chapel Hill, NC 27514 USA. SW Fdn Biomed Res, Dept Genet, San Antonio, TX 78284 USA. MedStar Res Inst, Washington, DC USA. Univ Oklahoma, Hlth Sci Ctr, Coll Publ Hlth, Ctr Amer Indian Hlth Res, Oklahoma City, OK USA. Missouri Breaks Ind Res Inst, Timber Lake, SD USA. NHLBI, Epidemiol & Biometry Program, Bethesda, MD 20892 USA. RP North, KE (reprint author), Univ N Carolina, Dept Epidemiol, Hill Bank Amer Ctr, 137 E Franklin St,Suite 306, Chapel Hill, NC 27514 USA. EM kari_north@unc.edu OI Diego, Vincent/0000-0002-0007-2085 FU NHLBI NIH HHS [U01 HL41652, U01 HL65520, U01 HL65521, U01 HL41642, U01 HL065520, U01 HL41654]; NIMH NIH HHS [MH059490] NR 34 TC 6 Z9 8 U1 0 U2 0 PU NORTH AMER ASSOC STUDY OBESITY PI SILVER SPRING PA 8630 FENTON ST, SUITE 918, SILVER SPRING, MD 20910 USA SN 1071-7323 J9 OBES RES JI Obes. Res. PD NOV PY 2005 VL 13 IS 11 BP 1877 EP 1884 DI 10.1038/oby.2005.230 PG 8 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 993US UT WOS:000233981300003 PM 16339117 ER PT J AU Hasler, G Lissek, S Ajdacic, V Milos, G Gamma, A Eich, D Rossler, W Angst, J AF Hasler, G Lissek, S Ajdacic, V Milos, G Gamma, A Eich, D Rossler, W Angst, J TI Major depression predicts an increase in long-term body weight variability in young adults SO OBESITY RESEARCH LA English DT Article DE body weight changes; major depression; antidepressants; exercise; weight cycling ID ZURICH COHORT; MASS INDEX; RISK; OBESITY; WOMEN; MEN; POPULATION; OVERWEIGHT; SYMPTOMS; PSYCHOPATHOLOGY AB Objective: To test the hypothesis that major depression predicts an increase in long-term body weight variability (BWV). Research Methods and Procedures: This was a prospective community-based single-age cohort study of young adults (N = 591) followed between the ages of 19 and 40. Following initial screening, information was derived from six subsequent semistructured diagnostic interviews conducted by mental health professionals. Major depression was diagnosed on the basis of DSM criteria. BWV was defined as the root mean square error of a regression line fitted to each individual's BMI values over time. Multiple regression analysis was used to test the association between major depression and BWV while controlling for potentially confounding variables including antidepressant treatment, eating disorder symptoms, and physical activity. We used random effects models to determine the temporal relationship between repeated measures of major depression and body weight change. Results: A highly significant positive association between major depression and BWV was found, whereas major depression was not associated with BMI level or BMI trend. Depression severity showed a dose-response-type relationship with the magnitude of BWV. After controlling for potentially confounding variables including antidepressant use, eating disorder symptoms, smoking, and physical activity, major depression remained a significant predictor of BWV (beta = 0.13, p < 0.001). Longitudinal Analysis revealed a unidirectional association between major depression and a later increase in body weight change rate irrespective of antidepressant medication. Discussion: Results from this study implicate depression as an important risk factor for increased BWV. Given increasing evidence for a link between major depression and both diabetes and cardiovascular disease, current results encourage further research on depression, BWV, and negative health outcomes. C1 NIMH, Intramural Res Program, Mood Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA. Univ Zurich, Hosp Psychiat, Zurich, Switzerland. Univ Zurich, Dept Psychiat, Eating Disorders Unit, Zurich, Switzerland. RP Hasler, G (reprint author), NIMH, Intramural Res Program, Mood Anxiety Disorders Program, NIH, 15K North Dr,Room 200,MSC 2670, Bethesda, MD 20892 USA. EM g.hasler@bluewin.ch RI Lissek, Shmuel/B-6577-2008; Hasler, Gregor/E-4845-2012; OI Hasler, Gregor/0000-0002-8311-0138; Ajdacic-Gross, Vladeta/0000-0002-7032-9237 NR 46 TC 17 Z9 17 U1 0 U2 1 PU NORTH AMER ASSOC STUDY OBESITY PI SILVER SPRING PA 8630 FENTON ST, SUITE 918, SILVER SPRING, MD 20910 USA SN 1071-7323 J9 OBES RES JI Obes. Res. PD NOV PY 2005 VL 13 IS 11 BP 1991 EP 1998 DI 10.1038/oby.2005.244 PG 8 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 993US UT WOS:000233981300017 PM 16339131 ER PT J AU Lee, WJ Colt, JS Heineman, EF McComb, R Weisenburger, DD Lijinsky, W Ward, MH AF Lee, WJ Colt, JS Heineman, EF McComb, R Weisenburger, DD Lijinsky, W Ward, MH TI Agricultural pesticide use and risk of glioma in Nebraska, United States SO OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID ADULT BRAIN-TUMORS; INTERNATIONAL CASE-CONTROL; N-NITROSO COMPOUNDS; PROPORTIONATE MORTALITY; OCCUPATIONAL EXPOSURE; CANCER-MORTALITY; NEW-ZEALAND; FARMERS; SWEDEN; NITROSAMINES AB Background: To evaluate the risk of the adult glioma associated with farming and agricultural pesticide use, the authors conducted a population based case control study in eastern Nebraska. Methods: Telephone interviews were conducted with men and women diagnosed with gliomas (n=251) between 1988 and 1993 and controls (n=498) randomly selected from the same geographical area. Unconditional logistic regression was used to calculate adjusted odds ratios (ORs) for farming and for use of individual and chemical classes of insecticides and herbicides, including pesticides classified as nitrosatable (able to form N-nitroso compounds upon reaction with nitrite). Non-farmers were used as the reference category for all analyses. Results: Among men, ever living or working on a farm and duration of farming were associated with significantly increased risks of glioma (>= 55 years on a farm OR=3.9, 95% CI 1.8 to 8.6); however, positive findings were limited to proxy respondents. Among women, there were no positive associations with farming activities among self or proxy respondents. Specific pesticide families and individual pesticides were associated with significantly increased risks among male farmers; however, most of the positive associations were limited to proxy respondents. For two herbicides and three insecticides, use was positively associated with risk among both self and proxy respondents. Based on a small number of exposed cases, ORs were significantly increased for the herbicides metribuzin (OR=3.4, 95% CI 1.2 to 9.7) and paraquat (OR=11.1, 95% CI 1.2 to 101), and for the insecticides bufencarb (OR=18.9, 95% CI 1.9 to 187), chlorpyrifos (OR=22.6, 95% CI 2.7 to 191), and coumaphos (OR=5.9, 95% CI 1.1 to 32). Conclusion: The authors found significant associations between some specific agricultural pesticide exposures and the risk of glioma among male farmers but not among female farmers in Nebraska; however, most of the positive associations were limited to proxy respondents. These findings warrant further evaluation in prospective cohort studies where issues of recall bias are not a concern. C1 NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. Korea Univ, Coll Med, Dept Prevent Med, Seoul 136701, South Korea. Univ Nebraska, Med Ctr, Omaha, NE USA. RP Ward, MH (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd EPS 8104, Rockville, MD 20852 USA. EM wardm@mail.nih.gov NR 52 TC 1 Z9 1 U1 1 U2 3 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1351-0711 J9 OCCUP ENVIRON MED JI Occup. Environ. Med. PD NOV PY 2005 VL 62 IS 11 DI 10.1136/oem.2005.020230 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 979HJ UT WOS:000232932700008 ER PT J AU Vermeulen, R Kromhout, H AF Vermeulen, R Kromhout, H TI Historical limitations of determinant based exposure groupings in the rubber manufacturing industry SO OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID WORKERS; DUST; STRATEGIES; BITUMEN; TRENDS; FUME AB Aims: To study the validity of using a cross-sectional industry-wide exposure survey to develop exposure groupings for epidemiological purposes that extend beyond the time period in which the exposure data were collected. Methods: Exposure determinants were used to group workers into high, medium, and low exposure groups. The contrast of this grouping and other commonly used grouping schemes based on plant and department within this exposure survey and a previously conducted survey within the same industry ( and factories) were estimated and compared. Results: Grouping of inhalable and dermal exposure based on exposure determinants resulted in the highest, but still modest, contrast (epsilon similar to 0.3). Classifying subjects based on a combination of plant and department resulted in a slightly lower contrast (epsilon similar to 0.2). If the determinant based grouping derived from the 1997 exposure survey was used to classify workers in the 1988 survey the average contrast decreased significantly for both exposures (epsilon similar to 0.1). On the contrary, the exposure classification based on plant and department increased in contrast (from epsilon similar to 0.2 to epsilon similar to 0.3) and retained its relative ranking overtime. Conclusions: Although determinant based groupings seem to result in more efficient groupings within a cross-sectional survey, they have to be used with caution as they might result in significant less contrast beyond the studied population or time period. It is concluded that a classification based on plant and department might be more desirable for retrospective studies in the rubber manufacturing industry, as they seem to have more historical relevance and are most likely more accurately recorded historically than information on exposure determinants in a particular industry. C1 NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Rockville, MD 20892 USA. Univ Utrecht, Inst Risk Assessment Sci, Environm & Occupat Hlth Grp, Utrecht, Netherlands. RP Vermeulen, R (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, 6120 Execut Blvd, Rockville, MD 20892 USA. EM vermeulr@mail.nih.gov RI Kromhout, Hans/A-9159-2008; Vermeulen, Roel/F-8037-2011 OI Vermeulen, Roel/0000-0003-4082-8163 NR 19 TC 2 Z9 2 U1 0 U2 3 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1351-0711 J9 OCCUP ENVIRON MED JI Occup. Environ. Med. PD NOV PY 2005 VL 62 IS 11 DI 10.1136/oem.2004.016329 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 979HJ UT WOS:000232932700009 ER PT J AU Sokolov, MV Smilenov, LB Hall, EJ Panyutin, IG Bonner, WM Sedelnikova, OA AF Sokolov, MV Smilenov, LB Hall, EJ Panyutin, IG Bonner, WM Sedelnikova, OA TI Ionizing radiation induces DNA double-strand breaks in bystander primary human fibroblasts SO ONCOGENE LA English DT Article DE bystander effect; DNA double-strand break; gamma-H2AX ID MEDIATED INTERCELLULAR COMMUNICATION; TARGETED CYTOPLASMIC IRRADIATION; HISTONE H2AX PHOSPHORYLATION; C3H 10T(1)/(2) CELLS; ALPHA-PARTICLES; GENOMIC INSTABILITY; MAMMALIAN-CELLS; NONIRRADIATED CELLS; DAMAGE; INDUCTION AB That irradiated cells affect their unirradiated 'bystander' neighbors is evidenced by reports of increased clonogenic mortality, genomic instability, and expression of DNA-repair genes in the bystander cell populations. The mechanisms underlying the bystander effect are obscure, but genomic instability suggests DNA double-strand breaks (DSBs) may be involved. Formation of DSBs induces the phosphorylation of the tumor suppressor protein, histone H2AX and this phosphorylated form, named gamma-H2AX, forms foci at DSB sites. Here we report that irradiation of target cells induces gamma-H2AX focus formation in bystander cell populations. The effect is manifested by increases in the fraction of cells in a population that contains multiple gamma-H2AX foci. After 18 h coculture with cells irradiated with 20 alpha-particles, the fraction of bystander cells with multiple foci increased 3.7-fold. Similar changes occurred in bystander populations mixed and grown with cells irradiated with gamma-rays, and in cultures containing media conditioned on gamma-irradiated cells. DNA DSB repair proteins accumulated at gamma-H2AX foci, indicating that they are sites of DNA DSB repair. Lindane, which blocks gap-junctions, prevented the bystander effect in mixing but not in media transfer protocols, while c-PTIO and aminoguanidine, which lower nitric oxide levels, prevented the bystander effect in both protocols. Thus, multiple mechanisms may be involved in transmitting bystander effects. These studies show that H2AX phosphorylation is an early step in the bystander effect and that the DNA DSBs underlying gamma-H2AX focus formation may be responsible for its downstream manifestations. C1 NCI, Mol Pharmacol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. NIH, Dept Nucl Med, Ctr Clin, Bethesda, MD 20892 USA. Inst Cell Biol & Genet Engn, Dept Radiat Biol & Biophys, UA-03143 Kiev, Ukraine. Columbia Univ, Coll Phys & Surg, Ctr Radiol Res, New York, NY 10032 USA. RP Bonner, WM (reprint author), NCI, Mol Pharmacol Lab, Canc Res Ctr, NIH, Bldg 37 Room 5050,9000 Rockville Pike, Bethesda, MD 20892 USA. EM bonnerw@mail.nih.gov; sedelnio@mail.nih.gov FU NIBIB NIH HHS [P41-EB002033] NR 46 TC 145 Z9 152 U1 0 U2 11 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD NOV PY 2005 VL 24 IS 49 BP 7257 EP 7265 DI 10.1038/sj.onc.1208886 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 982FA UT WOS:000233142100001 PM 16170376 ER PT J AU Schlom, J Arlen, PM Gulley, JL AF Schlom, J Arlen, PM Gulley, JL TI Novel vaccines for the treatment of gastrointestinal cancers - The Marshall article reviewed SO ONCOLOGY-NEW YORK LA English DT Editorial Material ID COLONY-STIMULATING FACTOR; CARCINOEMBRYONIC ANTIGEN; PROSTATE-CANCER; PHASE-I; IDENTIFICATION; ENHANCE C1 NCI, Tumor Immunol & Biol Lab, Clin Res Grp, Bethesda, MD 20892 USA. NCI, Canc Res Ctr, Clin Immunotherapy Grp, Tumor Immunol & Biol Lab, Bethesda, MD USA. RP Schlom, J (reprint author), NCI, Tumor Immunol & Biol Lab, Clin Res Grp, Bethesda, MD 20892 USA. RI Gulley, James/K-4139-2016 OI Gulley, James/0000-0002-6569-2912 NR 10 TC 0 Z9 0 U1 0 U2 0 PU P R R INC PI MELVILLE PA 48 SOUTH SERVICE RD, MELVILLE, NY 11747 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD NOV PY 2005 VL 19 IS 12 BP 1566 EP + PG 2 WC Oncology SC Oncology GA 052ET UT WOS:000238215000003 ER PT J AU Bachelier, R Xu, XL Li, CL Qiao, WH Furth, PA Lubet, RA Deng, CX AF Bachelier, R Xu, XL Li, CL Qiao, WH Furth, PA Lubet, RA Deng, CX TI Effect of bilateral oophorectomy on mammary tumor formation in BRCA1 mutant mice SO ONCOLOGY REPORTS LA English DT Article DE hormones; mutations; mammary gland ID BREAST-CANCER; MUTATION; GLAND; CELLS; WOMEN; RISK AB Germline mutations of breast cancer-associated gene 1 (BRCA1) predispose women to breast and ovarian cancer. It was recently shown that bilateral oophorectomy decreases breast cancer incidence in BRCA1 mutation carriers. To model human BRCA1 carriers, our laboratory has previously created mice with a conditional knockout of the full-length BRCA1 gene in the mammary epithelium combined with a heterozygous knockout of the p53 tumor suppressor gene. These mice developed ER-negative mammary tumors and were employed to determine the effects of oophorectomy on tumor formation. Individual knockout mice (BRCA1(Co/Co) MMTV-Crep53+/-), following two complete pregnancies, were either oophorectomized or sham treated. Mice were subsequently examined for the development of palpable mammary tumors until they were 12 months of age. Until 135 days post-oophorectomy (255 days of age), the tumor incidence was similar in both oophorectomized and intact mice, approximately 30%. After this time, the increase in tumor incidence was much lower in the oophorectomized mice, while tumor incidence increased in non-oophorectomized mice. The effects of oophorectomy on mammary development in both control and knockout mice were also examined. Oophorectomized mice with a conditional knockout of fulllength BRCA1 in conjunction with a loss of one p53 allele exhibited glandular regression with a reduction in the number of mammary epithelial cells following oophorectomy. This study employed a model that may be relevant for testing agents useful against breast cancer in BRCA1 carriers and a subset of sporadic cancers. The data also show that oophorectomy, if performed significantly prior to the time that tumors arise, appears to be quite effective. C1 NIDDK, Genet Dev & Dis Branch, Bethesda, MD 20892 USA. Georgetown Univ, Dept Oncol, Vincent T Lombardi Canc Res Ctr, Washington, DC 20057 USA. NCI, Div Canc Prevent & Control, Rockville, MD 20852 USA. RP Deng, CX (reprint author), NIDDK, Genet Dev & Dis Branch, Bethesda, MD 20892 USA. EM chuxiad@bdg10.niddk.nih.gov RI deng, chuxia/N-6713-2016 NR 18 TC 17 Z9 19 U1 0 U2 2 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1021-335X J9 ONCOL REP JI Oncol. Rep. PD NOV PY 2005 VL 14 IS 5 BP 1117 EP 1120 PG 4 WC Oncology SC Oncology GA 974KD UT WOS:000232589400003 PM 16211273 ER PT J AU Hemachandra, AH Klebanoff, MA Furth, SL AF Hemachandra, AH Klebanoff, MA Furth, SL TI Racial disparities in the association between birthweight in the full term infant and high blood pressure at age 7 years: Results from the United States Collaborative Perinatal Project SO PEDIATRIC RESEARCH LA English DT Meeting Abstract CT 3rd International Congress on Developmental Origins of Health and Disease CY NOV 16-19, 2005 CL Toronto, CANADA C1 Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA. NICHHD, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD NOV PY 2005 VL 58 IS 5 BP 1009 EP 1009 PG 1 WC Pediatrics SC Pediatrics GA 977CC UT WOS:000232779000032 ER PT J AU Jefferson, WN Padilla-Banks, E Goulding, EH Eddy, EM Newbold, RR AF Jefferson, WN Padilla-Banks, E Goulding, EH Eddy, EM Newbold, RR TI Neonatal exposure to the phytoestrogen genistein adversely affects fertilization rate and oocyte quality later in life SO PEDIATRIC RESEARCH LA English DT Meeting Abstract CT 3rd International Congress on Developmental Origins of Health and Disease CY NOV 16-19, 2005 CL Toronto, CANADA C1 NIEHS, Dev Endocrinol Sect, Mol Toxicol Lab, NIH DHHS RTP, Res Triangle Pk, NC 27709 USA. NIEHS, Gamete Biol Sect, Reprod & Dev Toxicol Lab, NIH DHHS RTP, Res Triangle Pk, NC 27709 USA. N Carolina State Univ, Dept Environm & Mol Toxicol, Raleigh, NC 27695 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD NOV PY 2005 VL 58 IS 5 BP 1025 EP 1026 PG 2 WC Pediatrics SC Pediatrics GA 977CC UT WOS:000232779000093 ER PT J AU Zhang, YW Graubard, BI Longnecker, MP Stanczyk, FZ Klebanoff, MA McGlynn, KA AF Zhang, YW Graubard, BI Longnecker, MP Stanczyk, FZ Klebanoff, MA McGlynn, KA TI Maternal hormone levels and perinatal characteristics: Implications for testicular cancer SO PEDIATRIC RESEARCH LA English DT Meeting Abstract CT 3rd International Congress on Developmental Origins of Health and Disease CY NOV 16-19, 2005 CL Toronto, CANADA C1 Yale Univ, Sch Med, New Haven, CT USA. NIEHS, DHHS, NIH, Res Triangle Pk, NC USA. Univ So Calif, Keck Sch Med, Los Angeles, CA USA. NICHHD, DHHS, NIH, Rockville, MD USA. NCI, DHHS, NIH, Rockville, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD NOV PY 2005 VL 58 IS 5 BP 1047 EP 1047 PG 1 WC Pediatrics SC Pediatrics GA 977CC UT WOS:000232779000166 ER PT J AU Troisi, R Douglass, C Hoover, RN AF Troisi, R Douglass, C Hoover, RN TI A case-control study of early life and growth factors and osteosarcoma SO PEDIATRIC RESEARCH LA English DT Meeting Abstract CT 3rd International Congress on Developmental Origins of Health and Disease CY NOV 16-19, 2005 CL Toronto, CANADA C1 NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. Harvard Sch Dent Med, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD NOV PY 2005 VL 58 IS 5 BP 1048 EP 1049 PG 2 WC Pediatrics SC Pediatrics GA 977CC UT WOS:000232779000171 ER PT J AU Salafia, CM Zhang, J Charles, AK Bresnahan, M Sun, WY Shrout, P Maas, EM AF Salafia, CM Zhang, J Charles, AK Bresnahan, M Sun, WY Shrout, P Maas, EM TI Placental growth and fetal growth: An approach to individualized placental growth-birth weight estimation SO PEDIATRIC RESEARCH LA English DT Meeting Abstract CT 3rd International Congress on Developmental Origins of Health and Disease CY NOV 16-19, 2005 CL Toronto, CANADA C1 Columbia Univ, Coll Phys & Surg, Dept Epidemiol, Mailman Sch Publ Hlth, New York, NY USA. NICHHD, Epidemiol Branch, NIH, Bethesda, MD 20892 USA. New York State Psychiat Inst & Hosp, New York, NY 10032 USA. Princess Margaret Hosp, Dept Pathol, Perth, WA, Australia. NYU, Dept Psychol, New York, NY 10003 USA. EarlyPath Clin & Res Diagnost, Larchmont, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD NOV PY 2005 VL 58 IS 5 BP 1064 EP 1065 PG 2 WC Pediatrics SC Pediatrics GA 977CC UT WOS:000232779000233 ER PT J AU Hemachandra, AH Howards, PP Schisterman, EF Klebanoff, MA AF Hemachandra, AH Howards, PP Schisterman, EF Klebanoff, MA TI Interaction between birth weight and postnatal growth does not increase risk for high blood pressure at age 7 years: Results from the United States collaborative perinatal project SO PEDIATRIC RESEARCH LA English DT Meeting Abstract CT 3rd International Congress on Developmental Origins of Health and Disease CY NOV 16-19, 2005 CL Toronto, CANADA C1 NICHHD, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD NOV PY 2005 VL 58 IS 5 BP 1102 EP 1103 PG 2 WC Pediatrics SC Pediatrics GA 977CC UT WOS:000232779000378 ER PT J AU Marston, SO Graubard, B Forman, M AF Marston, SO Graubard, B Forman, M TI The association between birthweight and puberty onset among girls in the United States SO PEDIATRIC RESEARCH LA English DT Meeting Abstract CT 3rd International Congress on Developmental Origins of Health and Disease CY NOV 16-19, 2005 CL Toronto, CANADA C1 NCI, Div Canc Prevent, NIH, Bethesda, MD 20892 USA. NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD NOV PY 2005 VL 58 IS 5 BP 1119 EP 1119 PG 1 WC Pediatrics SC Pediatrics GA 977CC UT WOS:000232779000436 ER PT J AU Newbold, RR Padilla-Banks, E Snyder, R Jefferson, WN AF Newbold, RR Padilla-Banks, E Snyder, R Jefferson, WN TI Developmental exposure to environmental estrogens is associated with obesity later in life SO PEDIATRIC RESEARCH LA English DT Meeting Abstract CT 3rd International Congress on Developmental Origins of Health and Disease CY NOV 16-19, 2005 CL Toronto, CANADA C1 NIEHS, Mol Toxicol Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD NOV PY 2005 VL 58 IS 5 BP 1126 EP 1126 PG 1 WC Pediatrics SC Pediatrics GA 977CC UT WOS:000232779000460 ER PT J AU Hunter, WM Helou, S Saluja, G Runyan, CW Coyne-Beasley, T AF Hunter, WM Helou, S Saluja, G Runyan, CW Coyne-Beasley, T TI Injury prevention advice in top-selling parenting books SO PEDIATRICS LA English DT Article DE injury prevention; safety; parenting books; TIPP; anticipatory guidance ID YOUNG-CHILDREN; AIR GUN; ADOLESCENTS; KNOWLEDGE; POSITION; FIREARMS; SAFETY AB Objective. Parenting books are a commonly used source of information on how to keep children and adolescents safe from injuries, the leading cause of death and disability for children aged 1 to 18 years. The content and the quality of the messages contained in these books have not been evaluated formally. The objective of this study was to determine the quantity and the quality of injury prevention messages contained in popular parenting books. Methods. Top-selling parenting books for 2 major booksellers were reviewed to determine the presence and the accuracy of injury prevention messages as compared with those recommended by the American Academy of Pediatrics (AAP) through The Injury Prevention Program ( TIPP) for younger children, aged 0 to 12 years, and the American Medical Association (AMA) through its Parent Package for the safety of adolescents. Results. Forty-six parenting books were reviewed, including 41 with messages related to younger children and 19 with messages related to adolescents. These books varied widely with regard to the number of injury prevention messages included. Although some books covered the great majority of TIPP messages for parents of young children, others included very few. In the case of books that address safety for adolescents, no book had more than half of the messages recommended by the AMA. Prevention of burns and motor vehicle injury were the most commonly addressed injury prevention topics in the books focused on younger children, whereas gun safety was the most prevalent injury prevention topic in books that focused on adolescents. Books that were authored by physicians addressed more of the recommended topics and messages than books that were written by authors from other professional backgrounds. The quality of messages was good, ie, consistent with the advice given by the AAP and the AMA. In only a few cases, the parenting books gave injury prevention advice that was inconsistent with recommendations. Conclusions. Overall, books on parenting adolescents are less likely to contain injury prevention messages than those that address younger children. However, the most frequent injury prevention messages for parents of adolescents describe strategies to prevent firearm injury, a leading cause of death for children in this age group. More emphasis should be placed on prevention of motor vehicle injuries, especially as relates to adolescents. Pediatricians and primary care physicians need to be aware of the strengths and weaknesses of parenting manuals in providing adequate guidance related to injury prevention. C1 Univ N Carolina, Injury Prevent Res Ctr, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Social Med, Sch Med, Chapel Hill, NC USA. Univ N Carolina, Sch Med, Dept Pediat, Chapel Hill, NC USA. Univ N Carolina, Sch Med, Dept Internal Med, Chapel Hill, NC USA. Univ N Carolina, Sch Publ Hlth, Dept Hlth Behav & Hlth Educ, Chapel Hill, NC USA. NICHHD, NIH, US Dept HHS, Bethesda, MD 20892 USA. RP Runyan, CW (reprint author), Univ N Carolina, Injury Prevent Res Ctr, bank Amer Bldg,Ste 500,137 E Franklin St, Chapel Hill, NC 27599 USA. EM carol_runyan@unc.edu FU ODCDC CDC HHS [R49/CCR402444 14-18] NR 36 TC 2 Z9 2 U1 3 U2 3 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD NOV PY 2005 VL 116 IS 5 BP 1080 EP 1088 DI 10.1542/peds.2004-1757 PG 9 WC Pediatrics SC Pediatrics GA 979WX UT WOS:000232976800005 PM 16263993 ER PT J AU Williams, DE Cadwell, BL Cheng, YLJ Cowie, CC Gregg, EW Geiss, LS Engelgau, MM Narayan, KMV Imperatore, G AF Williams, DE Cadwell, BL Cheng, YLJ Cowie, CC Gregg, EW Geiss, LS Engelgau, MM Narayan, KMV Imperatore, G TI Prevalence of impaired fasting glucose and its relationship with cardiovascular disease risk factors in US adolescents, 1999-2000 SO PEDIATRICS LA English DT Article DE children and adolescents; hyperglycemia; obesity; prevalence; survey ID DENSITY-LIPOPROTEIN CHOLESTEROL; AFFINITY-CHROMATOGRAPHY; DIABETES-MELLITUS; EXPERT COMMITTEE; LIFE-STYLE; TOLERANCE; CHILDHOOD; GLYCEMIA; INTERVENTION; POPULATION AB Objective. Several studies have reported increases in the occurrence of type 2 diabetes in youths. People with prediabetic states such as impaired fasting glucose (IFG) are at increased risk for developing diabetes and cardiovascular disease (CVD). The objective of this study was to examine the prevalence of IFG and its relationship with overweight and CVD risk factors in a nationally representative sample of US adolescents who were aged 12 to 19 years. Methods. We used data from the 1999 - 2000 National Health and Nutrition Examination Survey ( NHANES). Adolescents who had fasted for 8 hours or more were included in the study (n = 915). IFG was defined as a fasting glucose of 100 to 125 mg/dL. Participants were classified as overweight when their age- and gender-specific BMI was >= 95th percentile and as at-risk for overweight when their BMI was >= 85th and < 95th percentile. Results. In 1999 - 2000, the prevalence of IFG in US adolescents was 7.0% and was higher in boys than in girls (10.0% vs 4.0%). Prevalence of IFG was higher in overweight adolescents (17.8%) but was similar in those with normal weight and those who were at risk for overweight (5.4% vs 2.8%). The prevalence of IFG was significantly different across racial/ethnic groups (13.0%, 4.2%, and 7% in Mexican Americans, non-Hispanic black individuals, and non-Hispanic white individuals, respectively). Adolescents with IFG had significantly higher mean hemoglobin A1c, fasting insulin, total and low-density lipoprotein cholesterol, triglycerides, and systolic blood pressure and lower high-density lipoprotein cholesterol than those with normal fasting glucose concentrations. Conclusions. These data, representing 27 million US adolescents, reveal a very high prevalence of IFG ( 1 in 10 boys and 1 in 25 girls) among adolescents; the condition affects 1 in every 6 overweight adolescents. Adolescents with IFG have features of insulin resistance and worsened CVD risk factors. Evidence for prevention is still forthcoming in this age group. C1 Ctr Dis Control & Prevent, Div Diabet Translat, NCCDPHP, Atlanta, GA 30341 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. RP Williams, DE (reprint author), Ctr Dis Control & Prevent, Div Diabet Translat, NCCDPHP, 4770 Buford Hwy,NE MS-K10, Atlanta, GA 30341 USA. EM dewilliams@cdc.gov RI Narayan, K.M. Venkat /J-9819-2012 OI Narayan, K.M. Venkat /0000-0001-8621-5405 NR 34 TC 99 Z9 104 U1 0 U2 5 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD NOV PY 2005 VL 116 IS 5 BP 1122 EP 1126 DI 10.1542/peds.2004-2001 PG 5 WC Pediatrics SC Pediatrics GA 979WX UT WOS:000232976800010 PM 16263998 ER PT J AU Wootton, SH Gonzalez, BE Pawlak, R Teeter, LD Smith, KC Musser, JM Starke, JR Graviss, EA AF Wootton, SH Gonzalez, BE Pawlak, R Teeter, LD Smith, KC Musser, JM Starke, JR Graviss, EA TI Epidemiology of pediatric tuberculosis using traditional and molecular techniques: Houston, Texas SO PEDIATRICS LA English DT Article DE epidemiology; infectious disease; pediatric; tuberculosis ID FOREIGN-BORN PERSONS; NEW-YORK-CITY; MYCOBACTERIUM-TUBERCULOSIS; UNITED-STATES; STRAIN DIFFERENTIATION; TRANSMISSION DYNAMICS; COMPLEX STRAINS; GENETIC-MARKERS; CHILDREN; POPULATION AB Objective. To investigate the transmission dynamics of pediatric tuberculosis ( TB) by analyzing the clinical characteristics with the molecular profiles of Mycobacterium tuberculosis isolates during a 5-year period. Methods. A retrospective review of a prospective population-based active surveillance and molecular epidemiology project was conducted in private and public pediatric clinics within Houston and Harris County, Texas. The study population consisted of patients who had pediatric TB diagnosed from October 1, 1995, through September 30, 2000. Cases and potential source cases (PSC) were interviewed using a standardized questionnaire. Available Mycobacterium tuberculosis isolates from cases and PSCs were characterized and compared by IS6110 restriction fragment length polymorphism, spoligotyping, and genetic group assignment. Clinical characteristics were described, and molecular characterizations were compared. Data were analyzed by using EpiInfo 6.02b and SAS 8.2. Results. A total of 220 (92%) of 238 pediatric TB cases were included. Epidemiologic and clinical findings were consistent with previous studies. Molecular profiles from 3 cases did not match the profile of PSC. Four previously unknown PSCs were identified using molecular techniques. Fifty-one ( 71.8%) of 71 isolates matched at least 1 other Houston Tuberculosis Initiative TB database isolate and were grouped into 33 molecular clusters. Cases were more likely to be clustered when the patients were younger than 5 years, identified a source case, or were US born. Conclusions. Traditional contact tracing may not always be accurate, and molecular characterization can lead to identification of previously unrecognized source cases. Recent transmission plays a significant role in the transmission of TB to children as evident by the high degree of clustering found in our study population. C1 Baylor Coll Med, Dept Pathol 209E, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Dept Pediat, Infect Dis Sect, Houston, TX 77030 USA. Texas Childrens Hosp, Houston, TX 77030 USA. Univ Texas, Houston Med Sch, Dept Pediat, Houston, TX USA. NIAID, Rocky Mt Labs, NIH, Hamilton, MT 59840 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 [AI 41168]; PHS HHS [N01-A0-02738] NR 39 TC 17 Z9 17 U1 0 U2 1 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD NOV PY 2005 VL 116 IS 5 BP 1141 EP 1147 DI 10.1542/peds.2004-2701 PG 7 WC Pediatrics SC Pediatrics GA 979WX UT WOS:000232976800013 PM 16264001 ER PT J AU Morrison, JA Friedman, LA Harlan, WR Harlan, LC Barton, BA Schreiber, GB Klein, DJ AF Morrison, JA Friedman, LA Harlan, WR Harlan, LC Barton, BA Schreiber, GB Klein, DJ TI Development of the metabolic syndrome in black and white adolescent girls: A longitudinal assessment SO PEDIATRICS LA English DT Article DE metabolic syndrome; adolescence; overweight; insulin resistance; ethnicity ID NUTRITION EXAMINATION SURVEY; BLOOD-INSTITUTE GROWTH; BODY-FAT DISTRIBUTION; 3RD NATIONAL-HEALTH; SYNDROME SYNDROME-X; INSULIN-RESISTANCE; OBESITY; CHOLESTEROL; PREVALENCE; MORTALITY AB Background. The metabolic syndrome, associated with increased risk of type 2 diabetes mellitus and cardiovascular disease, begins to develop during adolescence. Objective. We sought to identify early predictors of the presence of the syndrome at the ages of 18 and 19 years in black and white girls. Methods. Using longitudinal data on participants from 2 centers in the National Heart, Lung, and Blood Institute Growth and Health Study, a 10-year cohort study, we applied cutoffs from the Adult Treatment Panel III to document changes in the prevalence of abnormal syndrome elements and the syndrome in girls aged 9 and 10 years, when cases were rare, and those aged 18 and 19 years, when prevalence had reached 3%. Longitudinal regression models identified early predictors for the presence of the syndrome. Results. Only 1 girl of each race had >= 3 factors at ages 9 and 10 ( 0.2%), but 20 black girls ( 3.5%) and 12 white girls ( 2.3%) had the syndrome 10 years later. Low high-density lipoprotein cholesterol was prevalent throughout the period in both black and white girls. The prevalence of other variables was low at enrollment but increased during follow-up, except for abnormal triglyceride levels in black girls, which remained low throughout follow-up. In multivariate models, early measures of waist circumference and triglyceride level were significant predictors for development of the syndrome. Conclusion. The strong association of central adiposity with the development of the metabolic syndrome suggests that early interventions aimed at managing pre-teen obesity could reduce risk of developing the syndrome. C1 Childrens Hosp, Med Ctr, Div Cardiol, Cincinnati, OH 45229 USA. Childrens Hosp, Med Ctr, Div Endocrinol, Cincinnati, OH 45229 USA. Univ Cincinnati, Med Ctr, Dept Pediat, Cincinnati, OH 45267 USA. Maryland Med Res Inst, Baltimore, MD USA. NIMH, Bethesda, MD 20892 USA. NCI, Bethesda, MD 20892 USA. Westat Corp, Rockville, MD USA. RP Morrison, JA (reprint author), Childrens Hosp, Med Ctr, Div Cardiol, OSB 4,3333 Burnet Ave, Cincinnati, OH 45229 USA. EM john.morrison@cchmc.org OI Barton, Bruce/0000-0001-7878-8895 FU NCRR NIH HHS [M01 RR 08084]; NHLBI NIH HHS [HC-55023-26, HL 48941] NR 23 TC 56 Z9 62 U1 0 U2 1 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD NOV PY 2005 VL 116 IS 5 BP 1178 EP 1182 DI 10.1542/peds.2004-2358 PG 5 WC Pediatrics SC Pediatrics GA 979WX UT WOS:000232976800018 PM 16264006 ER PT J AU Freeman, KB Rice, KC Riley, AL AF Freeman, KB Rice, KC Riley, AL TI Assessment of monoamine transporter inhibition in the mediation of cocaine-induced conditioned taste aversion SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE cocaine; conditioned taste aversion; monoamine transporter inhibition; GBR 12909; desipramine; clomipramine; dopamine; norepinephrine; serotonin ID PHARMACOLOGICAL CHARACTERIZATION; REUPTAKE INHIBITORS; STIMULUS PROPERTIES; RHESUS-MONKEYS; DOPAMINE; NOREPINEPHRINE; RATS; METHYLPHENIDATE; DESIPRAMINE; INVOLVEMENT AB Although the mechanisms of cocaine reward have been well characterizcd, the pharmacological basis of cocaine's aversive effects is less understood. Using the conditioned taste aversion (CTA) preparation, the present study examined the role of monoamine uptake inhibition in cocaine's aversive effects by comparing cocaine to three reuptake inhibitors with relative specificity for the transporters of dopamine (DAT; GBR 12909), norepinephrine (NET; desipramine) and serotonin (SERT, clomipramine). Specifically, 104 male Sprague-Dawley rats were given 20-min access to a novel saccharin solution followed immediately by a subcutaneous injection of cocaine, GBR 12909, desipramine, clomipramine (each at 18, 32 or 50 mg/kg; 12 groups) or drug vehicle (equivolume to the highest cocaine dose). Over trials, cocaine and desipramine each dose-dependently suppressed saccharin consumption and did so in an equivalent manner when matched by dose. However, both GBR 12909 and clomipramine conditioned weaker aversions than cocaine at the two lowest doses (18 and 32 mg/kg). At the highest dose (50 mg/kg), GBR 12909 produced equivalent suppression of saccharin consumption to cocaine while clomipramine's conditioned suppression remained relatively weak at this dose. These results suggest that cocaine's adrenergic actions resulting from NET inhibition may play a more significant role in the mediation of its aversive effects than its actions at DAT and SERT. (c) 2005 Elsevier Inc. All rights reserved. C1 American Univ, Dept Psychol, Psychopharmacol Lab, Washington, DC 20016 USA. NIDDK, Med Chem Lab, NIH, Bethesda, MD 20892 USA. RP Freeman, KB (reprint author), American Univ, Dept Psychol, Psychopharmacol Lab, Washington, DC 20016 USA. EM kf6802a@american.edu NR 40 TC 11 Z9 11 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD NOV PY 2005 VL 82 IS 3 BP 583 EP 589 DI 10.1016/j.pbb.2005.10.014 PG 7 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 002PO UT WOS:000234623700019 PM 16337262 ER PT J AU Sinha, G Leys, J Glorieux, C Thoen, J AF Sinha, G Leys, J Glorieux, C Thoen, J TI Dielectric spectroscopy of aerosil-dispersed liquid crystal embedded in Anopore membranes SO PHYSICAL REVIEW E LA English DT Article ID HYDROPHOBIC AEROSIL; QUENCHED DISORDER; LIGHT-SCATTERING; PHASE-TRANSITION; DYNAMICS; RELAXATION; ORDER; AEROGEL AB The complex dielectric permittivity epsilon(*) values are presented for aerosil-dispersed 4-pentyl-4(')-cyanobiphenyl (5CB) confined in Anopore membranes. The dielectric permittivities are measured in the frequency range from 10(-2) Hz to 1 GHz at temperatures ranging from 50 degrees C down to -20 degrees C. In bulk 5CB, which has only a nematic phase, there exist two main relaxation processes: one due to the rotation of molecules around their short axes for parallel orientation of the director to the probing field and another fast relaxation process due to the librational motion of molecules for perpendicular orientation. Inside Anopore membranes both these main relaxation processes can be observed, but with subtle differences. The relaxation process due to the rotation of molecules around the short axis is faster in Anopores at all temperatures in comparison with the bulk process. Hydrophilic aerosil particles, when dispersed in the liquid-crystal (LC) phase, attach to each other via hydrogen bonds and form a three-dimensional interconnecting aerosil network, thus dividing the LC phase into small domains. Dispersing 5CB with different concentrations of hydrophilic aerosils leads to a decrease in relaxation time with aerosil concentration. In these dispersed systems a slow additional relaxation process emerges. This slow process becomes stronger with higher concentrations of aerosil. From our experiments we conclude that this process is the relaxation of 5CB molecules homeotropically aligned to the surface of the aerosil particles. In the case of 5CB-aerosil dispersions enclosed in Anopore membranes this slow process still exists and increases also with aerosil concentration. The relaxation time of the rotation of the 5CB molecules around their short axis systematically increases in these 5CB-aerosil samples in Anopore membranes with aerosil concentration from the 5CB-Anopore behavior towards the behavior observed for 5CB-aerosil dispersions. We explain the evolution as resulting from opposing tendencies from size effects (in the Anopore membranes) and disorder effects (in the aerosil dispersions). C1 Katholieke Univ Leuven, Lab Akoestiek Therm Fys, Dept Natuurkunde & Sterrenkunde, B-3001 Louvain, Belgium. RP Sinha, G (reprint author), NIH, NIH Bldg 50,Rm 4151,MSC 8027,50 S Dr, Bethesda, MD 20892 USA. EM sinhag@nidcd.nih.gov NR 46 TC 38 Z9 38 U1 1 U2 6 PU AMERICAN PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 1539-3755 J9 PHYS REV E JI Phys. Rev. E PD NOV PY 2005 VL 72 IS 5 AR 051710 DI 10.1103/PhysRevE.72.051710 PN 1 PG 10 WC Physics, Fluids & Plasmas; Physics, Mathematical SC Physics GA 988LQ UT WOS:000233603100038 PM 16383623 ER PT J AU Mahady, GB Pendland, SL Stoia, A Hamill, FA Fabricant, D Dietz, BM Chadwick, LR AF Mahady, GB Pendland, SL Stoia, A Hamill, FA Fabricant, D Dietz, BM Chadwick, LR TI In vitro susceptibility of Helicobacter pylori to botanical extracts used traditionally for the treatment of gastrointestinal disorders SO PHYTOTHERAPY RESEARCH LA English DT Article DE Helicobacter pylori; traditional medicine; herbal; peptic ulcer disease ID UNIDENTIFIED CURVED BACILLI; NONULCER DYSPEPSIA; EFFICACY; INFECTION; GASTRITIS AB The gram-negative bacterium Helicobacter pylori (HP), identified in 1982, is now recognized as the primary etiological factor associated with the development of gastritis and peptic ulcer disease. In addition, HP infections are also associated with chronic gastritis, gastric carcinoma and primary gastric B-cell lymphoma. For centuries, herbals have been used in traditional medicine to treat a wide range of ailments, including gastrointestinal (GI) disorders such as dyspepsia, gastritis and peptic ulcer disease (PUD). However, the mechanism of action by which these botanicals exert their therapeutic effects has not been completely elucidated. As part of an ongoing screening program, the study assessed the in vitro susceptibility of 15 HP strains to botanical extracts, which have a history of traditional use in the treatment of GI disorders. Methanol extracts of Myristica fragrans (seed) had a MIC of 12.5 mu g/mL; Zingiber officinale (ginger rhizome/root) and Rosmarinus officinalis (rosemary leaf) had an MIC of 25 mu g/mL. Methanol extracts of botanicals with a MIC of 50 mu g/mL included Achillea millefolium, Foeniculum vulgare (seed), Passiflora incamata (herb), Origanum majorana (herb) and a (1:1) combination of Curcuma longa (root) and ginger rhizome. Botanical extracts with a MIC of 100 mu g/mL included Carum carvi (seed), Elettaria cardamoinum (seed), Gentiana lutea (roots), Juniper communis (berry), Lavandula angustifolia (flowers), Melissa officinalis (leaves), Mentha piperita (leaves) and Pimpinella anisum (seed). Methanol extracts of Matricaria recutita (flowers) and Ginkgo biloba (leaves) had a MIC > 100 mu g/mL. Copyright (c) 2005 John Wiley & Sons, Ltd. C1 Univ Illinois, Coll Pharm, Program Collaborat Res Pharmaceut Sci, NIH,Ctr Bot Dietary Supplements Res, Chicago, IL 60612 USA. Univ Illinois, Coll Pharm, Dept Pharm Practice, Chicago, IL 60612 USA. RP Mahady, GB (reprint author), Univ Illinois, Coll Pharm, Program Collaborat Res Pharmaceut Sci, NIH,Ctr Bot Dietary Supplements Res, 833 S Wood St,MC 877, Chicago, IL 60612 USA. EM mahady@uic.edu FU NCCIH NIH HHS [R21 AT000412-02] NR 21 TC 71 Z9 83 U1 6 U2 28 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0951-418X J9 PHYTOTHER RES JI Phytother. Res. PD NOV PY 2005 VL 19 IS 11 BP 988 EP 991 DI 10.1002/ptr.1776 PG 4 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 996HO UT WOS:000234165200014 PM 16317658 ER PT J AU Scaffidi, P Gordon, L Misteli, T AF Scaffidi, P Gordon, L Misteli, T TI The cell nucleus and aging: Tantalizing clues and hopeful promises SO PLOS BIOLOGY LA English DT Article ID HUTCHINSON-GILFORD-PROGERIA; LAMIN-A; ARCHITECTURE; LAMINOPATHY; FIBROBLASTS; INSTABILITY; MUTATIONS; PREVENTS; SHAPE C1 NCI, NIH, Bethesda, MD 20892 USA. Brown Med Sch, Providence, RI USA. RP Misteli, T (reprint author), NCI, NIH, Bethesda, MD 20892 USA. EM mistelit@mail.nih.gov NR 22 TC 29 Z9 30 U1 1 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1544-9173 J9 PLOS BIOL JI PLoS. Biol. PD NOV PY 2005 VL 3 IS 11 BP 1855 EP 1859 AR e395 DI 10.1371/journal.pbio.0030395 PG 5 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 988OA UT WOS:000233609300002 PM 16277559 ER PT J AU Mabon, SA Misteli, T AF Mabon, SA Misteli, T TI Differential recruitment of pre-mRNA splicing factors to alternatively spliced transcripts in vivo SO PLOS BIOLOGY LA English DT Article ID INHERITED DEMENTIA FTDP-17; SR PROTEINS; FRONTOTEMPORAL DEMENTIA; HUMAN-DISEASE; SITES; TAU; MECHANISMS; MUTATIONS; PHOSPHORYLATION; OVEREXPRESSION AB Alternative splicing in mammalian cells has been suggested to be largely controlled by combinatorial binding of basal splicing factors to pre-mRNA templates. This model predicts that distinct sets of pre-mRNA splicing factors are associated with alternatively spliced transcripts. However, no experimental evidence for differential recruitment of splicing factors to transcripts with distinct splicing fates is available. Here we have used quantitative single-cell imaging to test this key prediction in vivo. We show that distinct combinations of splicing factors are recruited to sites of alternatively spliced transcripts in intact cells. While a subset of serine/arginine protein splicing factors, including SF2/ASF, SC35, and SRp20, is efficiently recruited to the tau gene when exon 10 is included, these factors are less frequently associated with tau transcription sites when exon 10 is excluded. In contrast, the frequency of recruitment of several other splicing factors is independent of splicing outcome. Mutation analysis of SF2/ASF shows that both protein - protein as well as protein - RNA interactions are required for differential recruitment. The differential behavior of the various splicing factors provides the basis for combinatorial occupancy at pre-mRNAs. These observations represent the first in vivo evidence for differential association of pre-mRNA splicing factors with alternatively spliced transcripts. They confirm a key prediction of a stochastic model of alternative splicing, in which distinct combinatorial sets of generic pre-mRNA splicing factors contribute to splicing outcome. C1 NCI, NIH, Bethesda, MD 20892 USA. RP Misteli, T (reprint author), NCI, NIH, Bethesda, MD 20892 USA. EM mistelit@mail.nih.gov FU Intramural NIH HHS; NCI NIH HHS [Z01 BC010309-07] NR 46 TC 25 Z9 25 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1544-9173 J9 PLOS BIOL JI PLoS. Biol. PD NOV PY 2005 VL 3 IS 11 BP 1893 EP 1901 AR e374 DI 10.1371/journal.pbio.0030374 PG 9 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 988OA UT WOS:000233609300008 PM 16231974 ER PT J AU Altan-Bonnet, G Germain, RN AF Altan-Bonnet, G Germain, RN TI Modeling T cell antigen discrimination based on feedback control of digital ERK responses SO PLOS BIOLOGY LA English DT Article ID CLASS-I COMPLEXES; IMMUNOLOGICAL SYNAPSE; SIGNAL-TRANSDUCTION; POSITIVE SELECTION; ADAPTER PROTEINS; RECEPTOR-BINDING; FOREIGN ANTIGEN; TCR BINDING; ACTIVATION; LIGANDS AB T-lymphocyte activation displays a remarkable combination of speed, sensitivity, and discrimination in response to peptide - major histocompatibility complex (pMHC) ligand engagement of clonally distributed antigen receptors ( T cell receptors or TCRs). Even a few foreign pMHCs on the surface of an antigen-presenting cell trigger effective signaling within seconds, whereas 1 x 10(5) - 1 x 10(6) self-pMHC ligands that may differ from the foreign stimulus by only a single amino acid fail to elicit this response. No existing model accounts for this nearly absolute distinction between closely related TCR ligands while also preserving the other canonical features of T-cell responses. Here we document the unexpected highly amplified and digital nature of extracellular signal-regulated kinase (ERK) activation in T cells. Based on this observation and evidence that competing positive- and negative-feedback loops contribute to TCR ligand discrimination, we constructed a new mathematical model of proximal TCR-dependent signaling. The model made clear that competition between a digital positive feedback based on ERK activity and an analog negative feedback involving SH2 domain-containing tyrosine phosphatase (SHP-1) was critical for defining a sharp ligand-discrimination threshold while preserving a rapid and sensitive response. Several nontrivial predictions of this model, including the notion that this threshold is highly sensitive to small changes in SHP-1 expression levels during cellular differentiation, were confirmed by experiment. These results combining computation and experiment reveal that ligand discrimination by T cells is controlled by the dynamics of competing feedback loops that regulate a high-gain digital amplifier, which is itself modulated during differentiation by alterations in the intracellular concentrations of key enzymes. The organization of the signaling network that we model here may be a prototypic solution to the problem of achieving ligand selectivity, low noise, and high sensitivity in biological responses. C1 NIAID, Lymphocyte Biol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Germain, RN (reprint author), NIAID, Lymphocyte Biol Sect, Immunol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM rgermain@niaid.nih.gov FU Intramural NIH HHS NR 69 TC 232 Z9 236 U1 3 U2 20 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1544-9173 J9 PLOS BIOL JI PLoS. Biol. PD NOV PY 2005 VL 3 IS 11 BP 1925 EP 1938 AR e356 DI 10.1371/journal.pbio.0030356 PG 14 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 988OA UT WOS:000233609300011 PM 16231973 ER PT J AU Sabeti, PC Walsh, E Schaffner, SF Varilly, P Fry, B Hutcheson, HB Cullen, M Mikkelsen, TS Roy, J Patterson, N Cooper, R Reich, D Altshuler, D O'Brien, S Lander, ES AF Sabeti, PC Walsh, E Schaffner, SF Varilly, P Fry, B Hutcheson, HB Cullen, M Mikkelsen, TS Roy, J Patterson, N Cooper, R Reich, D Altshuler, D O'Brien, S Lander, ES TI The case for selection at CCR5-Delta 32 SO PLOS BIOLOGY LA English DT Article ID HUMAN GENOME; NATURAL-SELECTION; HAPLOTYPE RECONSTRUCTION; POSITIVE SELECTION; MAP; ALLELE; GENE; RESISTANCE; SIGNATURES; ORIGIN AB The C-C chemokine receptor 5, 32 base-pair deletion (CCR5-Delta 32) allele confers strong resistance to infection by the AIDS virus HIV. Previous studies have suggested that CCR5-Delta 32 arose within the past 1,000 y and rose to its present high frequency (5% - 14%) in Europe as a result of strong positive selection, perhaps by such selective agents as the bubonic plague or smallpox during the Middle Ages. This hypothesis was based on several lines of evidence, including the absence of the allele outside of Europe and long-range linkage disequilibrium at the locus. We reevaluated this evidence with the benefit of much denser genetic maps and extensive control data. We find that the pattern of genetic variation at CCR5-Delta 32 does not stand out as exceptional relative to other loci across the genome. Moreover using newer genetic maps, we estimated that the CCR5-Delta 32 allele is likely to have arisen more than 5,000 y ago. While such results can not rule out the possibility that some selection may have occurred at C-C chemokine receptor 5 (CCR5), they imply that the pattern of genetic variation seen at CCR5-Delta 32 is consistent with neutral evolution. More broadly, the results have general implications for the design of future studies to detect the signs of positive selection in the human genome. C1 MIT, Broad Inst, Cambridge, MA 02139 USA. Harvard Univ, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. NCI, Lab Genom Divers, Frederick, MD 21701 USA. Loyola Univ, Sch Med, Dept Epidemiol & Prevent Med, Maywood, IL 60153 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Diabet Unit, Ctr Human Genet Res, Boston, MA 02114 USA. MIT, Dept Biol, Cambridge, MA USA. Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA USA. RP Sabeti, PC (reprint author), MIT, Broad Inst, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM pardis@broad.mit.edu RI Mikkelsen, Tarjei/A-1306-2007; Altshuler, David/A-4476-2009; Schaffner, Stephen/D-1189-2011; Varilly, Patrick/C-8118-2013 OI Mikkelsen, Tarjei/0000-0002-8133-3135; Altshuler, David/0000-0002-7250-4107; Varilly, Patrick/0000-0003-4619-8174 NR 32 TC 118 Z9 123 U1 7 U2 37 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1544-9173 J9 PLOS BIOL JI PLoS. Biol. PD NOV PY 2005 VL 3 IS 11 BP 1963 EP 1969 AR e378 DI 10.1371/journal.pbio.0030378 PG 7 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 988OA UT WOS:000233609300015 PM 16248677 ER PT J AU Huerta, MF Farber, GK Wilder, EL Kleinman, DV Grady, PA Schwartz, DA Tabak, LA AF Huerta, MF Farber, GK Wilder, EL Kleinman, DV Grady, PA Schwartz, DA Tabak, LA TI NIH Roadmap interdisciplinary research initiatives SO PLOS COMPUTATIONAL BIOLOGY LA English DT Editorial Material C1 NIMH, Bethesda, MD 20892 USA. Natl Ctr Res Resources, Bethesda, MD USA. NIDDK, Bethesda, MD 20892 USA. Natl Inst Hlth Roadmap Interdisciplinary Res Init, Bethesda, MD USA. NINR, Bethesda, MD 20892 USA. Inst Environm Hlth Sci, Bethesda, MD USA. Natl Inst Dent & Craniofacial Res, Bethesda, MD USA. NIH, Bethesda, MD 20892 USA. RP Huerta, MF (reprint author), NIMH, Bethesda, MD 20892 USA. EM mhuert1@mail.nih.gov NR 2 TC 5 Z9 5 U1 0 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-734X J9 PLOS COMPUT BIOL JI PLoS Comput. Biol. PD NOV PY 2005 VL 1 IS 6 BP 449 EP 449 AR e59 DI 10.1371/journal.pcbi.0010059 PG 1 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA 003WS UT WOS:000234713300002 PM 16322762 ER PT J AU Parker, HG Ostrander, EA AF Parker, HG Ostrander, EA TI Canine genomics and genetics: Running with the pack SO PLOS GENETICS LA English DT Review ID COMPARATIVE CHROMOSOME MAP; LIMITED FOOD-CONSUMPTION; DOMESTIC DOG; HIP-DYSPLASIA; LINKAGE DISEQUILIBRIUM; POPULATION-STRUCTURE; LABRADOR-RETRIEVERS; RADIATION HYBRID; FAMILIARIS; DISEASE AB The domestication of the dog from its wolf ancestors is perhaps the most complex genetic experiment in history, and certainly the most extensive. Beginning with the wolf, man has created dog breeds that are hunters or herders, big or small, lean or squat, and independent or loyal. Most breeds were established in the 1800s by dog fanciers, using a small number of founders that featured traits of particular interest. Popular sire effects, population bottlenecks, and strict breeding programs designed to expand populations with desirable traits led to the development of what are now closed breeding populations, with limited phenotypic and genetic heterogeneity, but which are ideal for genetic dissection of complex traits. In this review, we first discuss the advances in mapping and sequencing that accelerated the field in recent years. We then highlight findings of interest related to disease gene mapping and population structure. Finally, we Summarize novel results oil the genetics of morphologic variation. C1 NHGRI, NIH, Bethesda, MD 20892 USA. RP Ostrander, EA (reprint author), NHGRI, NIH, Bethesda, MD 20892 USA. EM eostrand@mail.nih.gov RI Parker, Heidi/C-6954-2008; OI Ostrander, Elaine/0000-0001-6075-9738 FU Intramural NIH HHS NR 68 TC 65 Z9 66 U1 8 U2 50 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7390 J9 PLOS GENET JI PLoS Genet. PD NOV PY 2005 VL 1 IS 5 BP 507 EP 513 AR e58 DI 10.1371/journal.pgen.0010058 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 003XF UT WOS:000234714900001 PM 16311623 ER PT J AU Kraft, P Pharoah, P Chanock, SJ Albanes, D Kolonel, LN Hayes, RB Altshuler, D Andriole, G Berg, C Boeing, H Burtt, NP Bueno-de-Mesquita, B Calle, EE Cann, H Canzian, F Chen, YC Crawford, DE Dunning, AM Feigelson, HS Freedman, ML Gaziano, JM Giovannucci, E Gonzalez, CA Haiman, CA Hallmans, G Henderson, BE Hirschhorn, JN Hunter, DJ Kaaks, R Key, T Le Marchand, L Ma, J Overvad, K Palli, D Pike, MC Riboli, E Rodriguez, C Setiawan, WV Stampfer, MJ Stram, DO Thomas, G Thun, MJ Travis, R Trichopoulou, A Virtamo, J Wacholder, S AF Kraft, P Pharoah, P Chanock, SJ Albanes, D Kolonel, LN Hayes, RB Altshuler, D Andriole, G Berg, C Boeing, H Burtt, NP Bueno-de-Mesquita, B Calle, EE Cann, H Canzian, F Chen, YC Crawford, DE Dunning, AM Feigelson, HS Freedman, ML Gaziano, JM Giovannucci, E Gonzalez, CA Haiman, CA Hallmans, G Henderson, BE Hirschhorn, JN Hunter, DJ Kaaks, R Key, T Le Marchand, L Ma, J Overvad, K Palli, D Pike, MC Riboli, E Rodriguez, C Setiawan, WV Stampfer, MJ Stram, DO Thomas, G Thun, MJ Travis, R Trichopoulou, A Virtamo, J Wacholder, S TI Genetic variation in the HSD17B1 gene and risk of prostate cancer SO PLOS GENETICS LA English DT Article ID 17-BETA-HYDROXYSTEROID DEHYDROGENASE TYPES; GROWTH-FACTOR-I; BREAST-CANCER; MOLECULAR EPIDEMIOLOGY; MULTIETHNIC COHORT; ANDROGEN RECEPTOR; COMPLEX DISEASES; SRD5A2 GENE; EXPRESSION; POLYMORPHISMS AB Steroid hormones are believed to play an important role in prostate carcinogenesis, but epidemiological evidence linking prostate cancer and steroid hormone genes has been inconclusive, in part due to small sample sizes or incomplete characterization of genetic variation at the locus of interest. Here we report on the results of a comprehensive study of the association between HSD17B1 and prostate cancer by the Breast and Prostate Cancer Cohort Consortium, a large collaborative study. HSD17B1 encodes 17p-hydroxysteroid clehydrogenase 1, an enzyme that converts clihydroepiandrosterone to the testosterone precursor Delta 5-androsterone-3 beta, 17 beta-diol and converts estrone to estradiol. The Breast and Prostate Cancer Cohort Consortium researchers systematically characterized variation in HSD17B1 by targeted resequencing and dense genotyping; selected haplotype-tagging single nucleotide polymorphisms (htSNPs) that efficiently predict common variants in U.S. and European whites, Latinos, Japanese Americans, and Native Hawaiians; and genotyped these htSNPs in 8,290 prostate cancer cases and 9,367 study-, age-, and ethnicity-matched controls. We found no evidence that HSD17B1 htSNPs (including the nonsynonymous coding SNP S312G) or htSNP haplotypes were associated with risk of prostate cancer or tumor stage in the pooled multiethnic sample or in U.S. and European whites. Analyses stratified by age, body mass index, and family history of disease found no subgroup-specific associations between these HSD17B1 htSNPs and prostate cancer. We found significant evidence of heterogeneity in associations between HSD17B1 haplotypes and prostate cancer across ethnicity: one haplotype had a significant (p < 0.002) inverse association with risk of prostate cancer in Latinos and Japanese Americans but showed no evidence of association in African Americans, Native Hawaiians, or whites. However, the smaller numbers of Latinos and Japanese Americans in this study makes these subgroup analyses less reliable. These results suggest that the germline variants in HSD17B1 characterized by these htSNPs do not substantially influence the risk of prostate cancer in U.S. and European whites. C1 Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Boston, MA 02115 USA. Univ Cambridge, CRC Human Canc Genet Res Grp, Cambridge, England. NCI, Core Genotyping Facil, Gaithersburg, MD USA. NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. Univ Hawaii, Canc Res Ctr, Honolulu, HI USA. Harvard Univ, Broad Inst, Cambridge, MA USA. MIT, Cambridge, MA USA. Washington Univ, St Louis, MO USA. NCI, Div Canc Prevent, Bethesda, MD USA. German Inst Human Nutr, Dept Epidemiol, Potsdam, Germany. Whitehead MIT, Ctr Genome Res, Cambridge, MA USA. Natl Inst Publ Hlth & Environm, Ctr Nutr & Hlth, Bilthoven, Netherlands. Natl Home Off, Amer Canc Soc, Dept Epidemiol & Surveillance Res, Atlanta, GA USA. Ctr Etude Polymorphisme Humain, Fdn Jean Dausset, Paris, France. Int Agcy Res Canc, Genet Susceptibil Grp, Lyon, France. Anschutz Canc Pavillon, Aurora, CO USA. Univ Cambridge, Dept Oncol, Cambridge, England. Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. Brigham & Womens Hosp, Div Aging, Dept Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA USA. Hosp Llobregat, Catalan Inst Oncol, Barcelona, Spain. Univ So Calif, Keck Sch Med, Los Angeles, CA USA. Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden. Int Agcy Res Canc, Hormones & Canc Grp, Lyon, France. Canc Res UK, Epidemiol Unit, Oxford, England. Harvard Univ, Sch Med, Dept Med, Brigham & Womens Hosp,Channing Lab, Boston, MA USA. Aarhus Univ Hosp, Aalborg Hosp, Dept Clin Epidemiol, Aalborg, Denmark. CSPO Sci Inst Tuscany, Mol & Nutr Epidemiol Unit, Florence, Italy. Int Agcy Res Canc, Unit Nutr & Canc, Lyon, France. Amer Canc Soc, Atlanta, GA USA. Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Dept Prevent Med, Los Angeles, CA USA. Harvard Univ, Sch Med, Dept Epidemiol, Boston, MA USA. Univ So Calif, Keck Sch Med, Dept Prevent Med, Div Biostat & Genet Epidemiol, Los Angeles, CA USA. Univ Athens, Sch Med, Dept Hyg & Epidemiol, Athens, Greece. Natl Publ Hlth Inst, Canc Prevent Unit, Helsinki, Finland. RP Hayes, RB (reprint author), Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Boston, MA 02115 USA. EM hayesr@mail.nih.gov RI Altshuler, David/A-4476-2009; Chen, Yen-Ching/D-1098-2010; Albanes, Demetrius/B-9749-2015; OI Altshuler, David/0000-0002-7250-4107; Chen, Yen-Ching/0000-0002-8159-7202; Dunning, Alison Margaret/0000-0001-6651-7166; Hayes, Richard/0000-0002-0918-661X; PALLI, Domenico/0000-0002-5558-2437 FU NCI NIH HHS [U01 CA098216, U01 CA098233, U01 CA098710, U01 CA098758, UO1-CA98216, UO1-CA98233, UO1-CA98710, UO1-CA98758, R01 CA097193] NR 56 TC 43 Z9 45 U1 0 U2 0 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7390 EI 1553-7404 J9 PLOS GENET JI PLoS Genet. PD NOV PY 2005 VL 1 IS 5 BP 603 EP 613 AR e68 DI 10.1371/journal.pgen.0010068 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 003XF UT WOS:000234714900010 PM 16311626 ER PT J AU Shelburne, SA Sumby, P Sitkiewicz, I Granville, C DeLeo, FR Musser, JM AF Shelburne, SA Sumby, P Sitkiewicz, I Granville, C DeLeo, FR Musser, JM TI Central role of a bacterial two-component gene regulatory system of previously unknown function in pathogen persistence in human saliva SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE gene expression; Group A Streptococcus; microarray; Streptococcus pyogenes ID GROUP-A STREPTOCOCCUS; CYNOMOLGUS MACAQUES; IMMUNE-RESPONSE; PYOGENES; VIRULENCE; COLONIZATION; INFECTIONS; GROWTH; TRANSCRIPTOME; PHARYNGITIS AB The molecular genetic mechanisms used by bacteria to persist in humans are poorly understood. Group A Streptococcus (GAS) causes the majority of bacterial pharyngitis cases in humans and is prone to persistently inhabit the upper respiratory tract. To gain information about how GAS survives in and infects the oropharynx, we analyzed the transcriptome of a serotype M1 strain grown in saliva. The dynamic pattern of changes in transcripts of genes [spy0874/0875, herein named sptR and sptS (sptR/S), for saliva persistence] encoding a two-component gene regulatory system of unknown function suggested that SptR/S contributed to persistence of GAS in saliva. Consistent with this idea, an isogenic nonpolar mutant strain (Delta sptR) was dramatically less able to survive in saliva compared with the parental strain. Iterative expression microarray analysis of bacteria grown in saliva revealed that transcripts of several known and putative GAS virulence factor genes were decreased significantly in the Delta sptR mutant strain. Compared with the parental strain, the isogenic mutant strain also had altered transcripts of multiple genes encoding proteins involved in complex carbohydrate acquisition and utilization pathways. Western immunoblot analysis and real-time PCR analysis of GAS in throat swabs taken from humans with pharyngitis confirmed the findings. We conclude that SptR/S optimizes persistence of GAS in human saliva, apparently by strategically influencing metabolic pathways and virulence factor production. The discovery of a genetic program that significantly increased persistence of a major human pathogen in saliva enhances understanding of how bacteria survive in the host and suggests new therapeutic strategies. C1 Methodist Hosp, Res Inst, Ctr Mol & Translat Human Infect Dis Res, Houston, TX 77030 USA. Methodist Hosp, Dept Pathol, Houston, TX 77030 USA. Baylor Coll Med, Ctr Human Bacterial Pathogenesis, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Ctr Human Bacterial Pathogenesis, Dept Pathol, Houston, TX 77030 USA. NIAID, Rocky Mt Labs, Lab Human Bacterial Pathogenesis, Hamilton, MT 59840 USA. RP Musser, JM (reprint author), Methodist Hosp, Res Inst, Ctr Mol & Translat Human Infect Dis Res, 6535 Fannin, Houston, TX 77030 USA. EM jmmusser@tmh.tmc.edu RI Sitkiewicz, Izabela/G-5058-2011; OI Sitkiewicz, Izabela/0000-0001-8228-9917; DeLeo, Frank/0000-0003-3150-2516 FU NCRR NIH HHS [K12-RR17665, K12 RR017665]; NIAID NIH HHS [K08 AI064564]; PHS HHS [UO1-A160595, T32-19503] NR 33 TC 57 Z9 60 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 NOV 1 PY 2005 VL 102 IS 44 BP 16037 EP 16042 DI 10.1073/pnas.0505839102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 981LU UT WOS:000233090900058 PM 16249338 ER PT J AU Li, M Rasulova, F Melnikov, EE Rotanova, TV Gustchina, A Maurizi, MR Wlodawer, A AF Li, M Rasulova, F Melnikov, EE Rotanova, TV Gustchina, A Maurizi, MR Wlodawer, A TI Crystal structure of the N-terminal domain of E-coli Lon protease SO PROTEIN SCIENCE LA English DT Article DE ATP-dependent proteases; protein domain; structural genomics ID DEPENDENT PROTEASES; ACTIVE-SITES; CLASSIFICATION; PROTEOLYSIS; REFINEMENT; RESOLUTION; ATPASES; SEARCH; AAA(+); DYAD AB We report here the first crystal structure of the N-terminal domain of an A-type Lon protease. Lon proteases are ubiquitous, multidomain, ATP-dependent enzymes with both highly specific and nonspecific protein binding, unfolding, and degrading activities. We expressed and purified a stable, monomeric 119-amino acid N-terminal subdomain of the Escherichia coli A-type Lon protease and determined its crystal structure at 2.03 angstrom (Protein Data Bank [PDB] code 2ANE). The structure was solved in two crystal forms, yielding 14 independent views. The domain exhibits a unique fold consisting primarily of three twisted P-sheets and a single long alpha-helix. Analysis of recent PDB depositions identified a similar fold in BPP1347 (PDB code IZBO), a 203-amino acid protein of unknown function from Bordetella parapertussis, crystallized as part of a structural genomics effort. BPP1347 shares sequence homology with Lon N-domains and with a family of other independently expressed proteins of unknown functions. We postulate that, as is the case in Lon proteases, this structural domain represents a general protein and polypeptide interaction domain. C1 NCI, Macromol Crystallog Lab, Frederick, MD 21702 USA. SAIC Frederick, Basic Res Program, Frederick, MD 21702 USA. NCI, Cell Biol Lab, Bethesda, MD 20892 USA. Russian Acad Sci, Shemyakin Ovchinnikov Inst Bioorgan Chem, Moscow 117997, Russia. RP Wlodawer, A (reprint author), NCI, Macromol Crystallog Lab, Bldg 536,Room 5, Frederick, MD 21702 USA. EM wlodawer@ncifcrf.gov FU NCI NIH HHS [N01CO12400, N01 CO 12400] NR 28 TC 31 Z9 35 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD NOV PY 2005 VL 14 IS 11 BP 2895 EP 2900 DI 10.1110/ps.051736805 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 980CK UT WOS:000232991300013 PM 16199667 ER PT J AU Brosschot, JF Pieper, S Thayer, JF AF Brosschot, JF Pieper, S Thayer, JF TI Expanding stress theory: Prolonged activation and perseverative cognition SO PSYCHONEUROENDOCRINOLOGY LA English DT Article; Proceedings Paper CT Meeting on Somatisation, Sensitisation and Psychosomatic Medicine held in honor of Holger Ursin CY JUN 02-04, 2004 CL Bergen, NORWAY DE stress theory; prolonged physiological activation; recovery; anticipatory responses; worry; rumination; perseverative cognition ID HEART-RATE-VARIABILITY; CARDIOVASCULAR RECOVERY; CORTISOL SECRETION; DISEASE; MORTALITY; RESPONSES; EXERCISE; HEALTH; SLEEP; REACTIVITY AB Several theories of the stress-disease link have now incorporated prolonged activation. This article argues that these theories stilt tack an important element, that is, the cognitive nature of the mechanism that causes stress responses to be sustained. The perception of stress and the initial response to it do not automatically lead to prolonged activation. The active cognitive representations of stressors need to be prolonged in order to extend their physiological concomitants. We call this mediating process perseverative cognition, and it is manifested in phenomena such as worry, rumination, and anticipatory stress. We summarize evidence suggesting that these phenomena are indeed associated with physiological activation, including cardiovascular, endocrinological and immunological parameters. This evidence is stilt far from sufficient, due to the many methodological insufficiencies in the studies involved. Nevertheless, it makes clear that cognitive phenomena characterized by perseverative cognition may be likely candidates to mediate the effects of stress sources on somatic disease. We also argue that there is a dearth of evidence supporting the role of prolonged activation. There are a limited number of studies demonstrating prolonged activity related to stressors and emotional episodes, and their methodologies often do not allow unambiguous conclusions. Even more important, the crucial assumption that prolonged activation actually leads to pathogenic states and disease has received hardly any attention yet and therefore is stilt largely unsupported. There are only a few studies that showed that anticipatory responses and slow recovery from stress predicted disease states. (c) 2005 Elsevier Ltd. All rights reserved. C1 Leiden Univ, Dept Psychol, Div Clin & Hlth Psychol, NL-2300 RB Leiden, Netherlands. NIA, Baltimore, MD 21224 USA. RP Brosschot, JF (reprint author), Leiden Univ, Dept Psychol, Div Clin & Hlth Psychol, POB 9555, NL-2300 RB Leiden, Netherlands. EM brosschot@fsw.leidenuniv.nl; jt182f@nih.gov NR 34 TC 165 Z9 167 U1 8 U2 54 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4530 J9 PSYCHONEUROENDOCRINO JI Psychoneuroendocrinology PD NOV PY 2005 VL 30 IS 10 BP 1043 EP 1049 DI 10.1016/j.psyneuen.2005.04.008 PG 7 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA 954YB UT WOS:000231190300019 PM 15939546 ER PT J AU Thayer, JF Brosschot, JF AF Thayer, JF Brosschot, JF TI Psychosomatics and psychopathology: looking up and down from the brain SO PSYCHONEUROENDOCRINOLOGY LA English DT Article; Proceedings Paper CT Meeting on Somatisation, Sensitisation and Psychosomatic Medicine held in honor of Holger Ursin CY JUN 02-04, 2004 CL Bergen, NORWAY DE autonomic nervous system; heart rate variability; prefrontal inhibition; emotional regulation; prolonged physiological activation; health ID HEART-RATE-VARIABILITY; PERIOD VARIABILITY; PREFRONTAL CORTEX; WORKING-MEMORY; CARDIOVASCULAR-DISEASE; COGNITIVE FUNCTION; NEGATIVE MOOD; EMOTION; DEPRESSION; BEHAVIOR AB The autonomic nervous system (ANS) plays a rote in a wide range of somatic and mental diseases. Using a model of neurovisceral integration, this article describes how autonomic imbalance and decreased parasympathetic tone in particular may be the final common pathway linking negative affective states and conditions to ill health. The central nervous system (CNS) network that regulates autonomic balance (central autonomic network, CAN) is closely related and partially overlaps with networks serving executive, social, affective, attentional, and motivated behavior (anterior executive region, AER; and Damasio's [Damasio, A.R., 1998. Emotion in the perspective of an integrated nervous system. Brain Res. Rev. 26, 83-86.] 'emotion circuit'). A common reciprocal inhibitory cortico-subcortical neural circuit serves to regulate defensive behavior, including autonomic, emotional and cognitive features. This inhibitory cortico-subcortical circuit may structurally, as well as functionally, link psychological processes with health-related physiology. When the prefrontal cortex is taken 'offline' for whatever reason, parasympathetic inhibitory action is withdrawn and a relative sympathetic dominance associated with disinhibited defensive circuits is released, which can be pathogenic when sustained for long periods. This state is indicated by tow heart rate variability (HRV), which is a marker for low parasympathetic activation and prefrontal hypoactivity. Consistent with this, HRV is associated with a range of psychological and somatic pathological conditions, including immune dysfunction. Finally, we discuss supportive evidence from recent studies of the reflexive startle blink, attention and working memory, which shows that tow HRV predicts hypervigilance and inefficient allocation of attentional and cognitive resources. (c) 2005 Elsevier Ltd. All rights reserved. C1 NIA, GRC, LPC, Baltimore, MD 21224 USA. Leiden Univ, Leiden, Netherlands. RP Thayer, JF (reprint author), NIA, GRC, LPC, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM jt182f@nih.gov NR 71 TC 237 Z9 238 U1 4 U2 48 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4530 J9 PSYCHONEUROENDOCRINO JI Psychoneuroendocrinology PD NOV PY 2005 VL 30 IS 10 BP 1050 EP 1058 DI 10.1016/j.psyneuen.2005.04.014 PG 9 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA 954YB UT WOS:000231190300020 PM 16005156 ER PT J AU Torregrossa, MM Folk, JE Rice, KC Watson, SJ Woods, JH AF Torregrossa, MM Folk, JE Rice, KC Watson, SJ Woods, JH TI Chronic administration of the delta opioid receptor agonist (+)BW373U86 and antidepressants on behavior in the forced swim test and BDNF mRNA expression in rats SO PSYCHOPHARMACOLOGY LA English DT Article DE delta opioid receptor; (+)BW373U86; BDNF; antidepressant; forced swim test; in situ hybridization ID GENE-EXPRESSION; DRUG-TREATMENT; BRAIN; TRKB; ACTIVATION; DEPRESSION; SEIZURES; MODELS; KINASE; LENGTH AB Rationale: Selective delta opioid receptor agonists have been shown to produce antidepressant-like behavioral effects and increase brain-derived neurotrophic factor (BDNF) mRNA expression when given acutely, but the chronic effects of delta agonists have been less well characterized. Objective: The present study examined the effects of chronic exposure to the delta agonist (+)BW 373U86 (BW) on antidepressant-like behavior in the forced swim test and on BDNF mRNA expression in comparison to chronic treatment with the antidepressants fluoxetine, desipramine, bupropion, and tranylcypromine. Methods: Sprague-Dawley rats were treated chronic ally with one of the above treatments and were tested for antidepressant effects in the forced swim test, and assayed for BDNF mRNA expression by in situ hybridization. Results: Acute administration of 10 mg/kg BW produced a significant antidepressant-like effect in the forced swim test, while chronic (8- or 21-day) BW administration did not produce a significant antidepressant-like effect. When 10 mg/kg BW was administered for 8 days, it produced a significant increase in BDNF mRNA expression in the frontal cortex, while having no effect on BDNF expression when given for 21 days. Chronic bupropion and desipramine significantly decreased BDNF expression in the dentate gyrus of the hippocampus, while fluoxetine had no effect in any brain region. Chronic tranylcypromine produced a significant increase in BDNF expression in the CA1 region of the hippocampus. Conclusions: Chronic exposure to BW produces tolerance to most effects, although at differential rates. In addition, increased BDNF mRNA expression does not appear to be a common effect of chronic administration of various antidepressants. C1 Univ Michigan, Sch Med, Dept Pharmacol, Ann Arbor, MI 48109 USA. Univ Michigan, Program Neurosci, Ann Arbor, MI 48109 USA. NIDDK, NIH, DHHS, Bethesda, MD USA. Univ Michigan, Mental Hlth Res Inst, Ann Arbor, MI 48109 USA. RP Woods, JH (reprint author), Univ Michigan, Sch Med, Dept Pharmacol, 1301 MSRB 3, Ann Arbor, MI 48109 USA. EM jhwoods@umich.edu FU NIDA NIH HHS [R01 DA013386, DA13386, P50 DA000254, K21 DA000254, DA07281, T32 DA007281, P01 DA000254, DA00254]; NIMH NIH HHS [P01 MH042251, MH42251] NR 29 TC 20 Z9 21 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD NOV PY 2005 VL 183 IS 1 BP 31 EP 40 DI 10.1007/s00213-005-0113-5 PG 10 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 988BK UT WOS:000233566200004 PM 16220339 ER PT J AU Newton, TF Roache, JD De La Garza, R Fong, T Wallace, CL Li, SH Elkashef, A Chiang, N Kahn, R AF Newton, TF Roache, JD De La Garza, R Fong, T Wallace, CL Li, SH Elkashef, A Chiang, N Kahn, R TI Safety of intravenous methamphetamine administration during treatment with bupropion SO PSYCHOPHARMACOLOGY LA English DT Article DE methamphetamine; bupropion; drug abuse; safety evaluation; pharmacokinetics ID SMOKING-CESSATION; DOPAMINE; DEPENDENCE; RELEASE; COCAINE; MODEL; AMPHETAMINE; IMIPRAMINE; TOXICITY; CYP2D6 AB Rationale: Methamphetamine dependence is a growing problem for which no medication treatments have proven effective. Objectives: We evaluated bupropion, an antidepressant with beneficial effects for the treatment of nicotine dependence, in patients with methamphetamine dependence, to assess the safety and tolerability of methamphetamine administration during bupropion treatment. Methods: Twenty-six participants entered the study and 20 completed the protocol. Participants received intravenous methamphetamine (0, 15, and 30 mg) before and after randomization to twice-daily bupropion (15 0 mg SR) or matched placebo. Dependent measures included cardiovascular effects of methamphetamine, methamphetamine and amphetamine phannacokinetics, and peak and trough plasma concentrations of bupropion and its metabolites. Results: Bupropion treatment was well tolerated, with bupropion- and placebo-treated groups reporting similar rates of adverse events. Methamphetamine administration was associated with expected stimulant cardiovascular effects, and these were not accentuated by bupropion treatment. Instead, there was a trend for bupropion to reduce methamphetamine-associated increases in blood pressure and a statistically significant reduction in methamphetamine-associated increases in heart rate. Pharmacokinetic analysis revealed that bupropion treatment reduced the plasma clearance of methamphetamine and also reduced the appearance of amphetamine in the plasma. Methamphetamine administration did not alter the peak and trough plasma concentrations of bupropion or its metabolites. Conclusions: Methamphetamine administration was well tolerated during bupropion treatment. There was no evidence of additive cardiovascular effects when the drugs were coadministered. This study provides initial evidence for the safety of prescribing bupropion for the treatment of methamphetamine abuse and dependence. The impact of bupropion treatment in patients who abuse larger doses of methamphetamine remains undetermined. C1 Univ Calif Los Angeles, Dept Psychiat & Behav Sci, David Geffen Sch Med, Los Angeles, CA 90024 USA. Univ Texas, Hlth Sci Ctr, Dept Psychiat, Univ Clin Psychopharmacol Lab, San Antonio, TX 78285 USA. Natl Inst Drug Abuse, Div Pharmacotherapies & Med Consequences Drug Abu, Bethesda, MD USA. RP Newton, TF (reprint author), Univ Calif Los Angeles, Dept Psychiat & Behav Sci, David Geffen Sch Med, Los Angeles, CA 90024 USA. EM tnewton@mednet.ucla.edu RI De La Garza, Richard/B-2489-2014; OI De La Garza, Richard/0000-0003-1943-4469; newton, thomas/0000-0002-3198-5901 FU NCRR NIH HHS [RR-00865]; NIDA NIH HHS [DA-08804, DA-00388, DA-18185] NR 28 TC 37 Z9 40 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD NOV PY 2005 VL 182 IS 3 BP 426 EP 435 DI 10.1007/s00213-005-0102-8 PG 10 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 982CQ UT WOS:000233135900013 PM 16163531 ER PT J AU Clark, L Roiser, JP Cools, R Rubinsztein, DC Sahakian, BJ Robbins, TW AF Clark, L Roiser, JP Cools, R Rubinsztein, DC Sahakian, BJ Robbins, TW TI Stop signal response inhibition is not modulated by tryptophan depletion or the serotonin transporter polymorphism in healthy volunteers: implications for the 5-HT theory of impulsivity SO PSYCHOPHARMACOLOGY LA English DT Article; Proceedings Paper CT 12th Annnual Meeting of the Cognitive-Neuroscience-Society CY APR 09-12, 2005 CL New York, NY SP Cognit Neurosci Soc ID MAJOR DEPRESSIVE DISORDER; 5-HYDROXYINDOLEACETIC ACID; CEREBROSPINAL-FLUID; GENETIC-VARIATION; PROMOTER POLYMORPHISM; 1ST-DEGREE RELATIVES; PROLACTIN RESPONSE; CONDUCT DISORDER; RAPID DEPLETION; FAMILY HISTORY AB Rationale: Reduced serotonin neurotransmission is implicated in disorders of impulse control, but the involvement of serotonin in inhibitory processes in healthy human subjects remains unclear. Objectives: To investigate the effects of an acute manipulation of serotonin and genotype at a functional polymorphism in a gene coding for the serotonin transporter (5-HTT) on an established measure of response inhibition. Methods: Serotonin function was reduced by the acute tryptophan depletion (ATD) procedure in a double-blind, crossover design in 42 healthy subjects. The Stop Signal Task (SST) was administered 57 h after drink administration. The influences of 5-HTT polymorphism, gender and trait impulsivity were investigated. Results: ATD was associated with significant depletion of plasma tryptophan levels but did not increase the stop signal reaction time in comparison to the balanced (placebo) amino acid mixture. Subjects possessing the short allele of the 5-HTT polymorphism were not more impulsive on the SST than subjects homozygous for the long allele under placebo conditions and were not disproportionately sensitive to the effects of ATD. There was no effect of gender or trait impulsivity on ATD-induced change. Conclusions: We find no support for the involvement of brain serotonin neurotransmission in this form of inhibitory control in healthy human subjects. C1 Univ Cambridge, Dept Expt Psychol, Cambridge CB2 3EB, England. Univ Cambridge, Dept Psychiat, Sch Clin Med, Cambridge, England. NIMH, Sect Mood & Anxiety Disorders, Rockville, MD 20852 USA. Univ Calif Berkeley, Helen Wills Neurosci Inst, Berkeley, CA 94720 USA. Addenbrookes Hosp, Dept Med Genet, Cambridge Inst Med Res, Cambridge, England. RP Clark, L (reprint author), Univ Cambridge, Dept Expt Psychol, Downing St, Cambridge CB2 3EB, England. EM lc260@cam.ac.uk RI Roiser, Jonathan/A-1791-2010; Cools, Roshan/D-1905-2010 FU Wellcome Trust NR 65 TC 121 Z9 121 U1 4 U2 11 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD NOV PY 2005 VL 182 IS 4 BP 570 EP 578 DI 10.1007/s00213-005-0104-6 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 986NW UT WOS:000233458000014 PM 16163530 ER PT J AU Jutkiewicz, EM Rice, KC Traynor, JR Woods, JH AF Jutkiewicz, EM Rice, KC Traynor, JR Woods, JH TI Separation of the convulsions and antidepressant-like effects produced by the delta-opioid agonist SNC80 in rats SO PSYCHOPHARMACOLOGY LA English DT Article DE delta-opioid receptor; antidepressants; convulsions; forced swim test; rats; SNC80; infusion rate ID LONG-TERM POTENTIATION; SPRAGUE-DAWLEY RATS; ENDOGENOUS ENKEPHALINS; SQUIRREL-MONKEYS; COCAINE; BW373U86; MICE; STIMULATION; RECEPTORS; RESPONSES AB Rationale: Delta-opioid agonists produce a number of behavioral effects, including convulsions, anti-nociception, locomotor stimulation, and anti-depressant-like effects. The development of these compounds as treatments for depression is limited by their convulsive effects. Therefore, determining how to separate the convulsive and antidepressant-like characteristics of these compounds is essential for their potential clinical use. Objective: The present study tests the hypothesis that the rate of delta-opioid agonist administration greatly contributes to the convulsive properties, but not the antidepressant-like effects, of delta-opioid agonists. Materials and methods: The delta-opioid agonist SNC80 (1, 3.2, and 10 mg kg(-1) or vehicle) was administered to Sprague-Dawley rats by intravenous infusion over different durations of time (20 s, 20, or 60 min). Convulsions were measured by observation prior to determining antidepressant-like effects in the forced swim test. Results: Slowing the rate of SNC80 administration minimized delta agonist-induced convulsions without altering the effects of SNC80 in the forced swim test. Conclusions: These data suggest that delta agonist-induced antidepressant properties are independent of convulsive effects, and that it may be possible to eliminate the convulsions produced by delta agonists, further promoting their potential clinical utility. C1 Univ Michigan, Sch Med, Dept Pharmacol, Ann Arbor, MI 48109 USA. NIH, Bethesda, MD 20892 USA. RP Jutkiewicz, EM (reprint author), Univ Michigan, Sch Med, Dept Pharmacol, 1301 MSRB 3, Ann Arbor, MI 48109 USA. EM ejutkiew@umich.edu FU NIDA NIH HHS [P01 DA000254, DA00254, K21 DA000254, P50 DA000254, T32 DA007267, T32 DA07267]; NIGMS NIH HHS [T32 GM007767, T32 GM07767] NR 24 TC 32 Z9 33 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD NOV PY 2005 VL 182 IS 4 BP 588 EP 596 DI 10.1007/s00213-005-0138-9 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 986NW UT WOS:000233458000016 PM 16163520 ER PT J AU Cameron, KA Haarmann, HJ Grafman, J Ruchkin, DS AF Cameron, KA Haarmann, HJ Grafman, J Ruchkin, DS TI Long-term memory is the representational basis for semantic verbal short-term memory SO PSYCHOPHYSIOLOGY LA English DT Article DE semantic; short-term memory; long-term memory; activation; event-related potentials ID EVENT-RELATED POTENTIALS; IMMEDIATE SERIAL-RECALL; WORKING-MEMORY; LEXICAL DECISION; RETRIEVAL THEORY; INFORMATION; REDINTEGRATION; MAINTENANCE; RETENTION; COMPONENT AB The present study supports activation models of verbal short-term memory that include a semantic contribution to the retention process. Event-related brain potentials were used to probe the level of activation of semantic representations of a series of words in a delay interval following their presentation. The levels of activation were compared in two tasks: (1) a short-term memory task that involved a semantic judgment in the recall phase following the delay interval, and (2) a nonmemory control task. The level of semantic activation during the delay interval was higher in the short-term memory task, indicating that enhanced activation of semantic representations is involved in the short-term storage of verbal information. This result implies that activated long-term memory provides a representational basis for semantic verbal short-term memory, and hence supports theories that postulate that short- and long-term stores are not separate. C1 Washington Coll, Dept Psychol, Chestertown, MD USA. Univ Maryland, Ctr Adv Study Living, Neurosci & Cognit Sci Program, College Pk, MD 20742 USA. Natl Inst Neurol Disorders & Stroke, Cognit Neurosci Sect, Bethesda, MD USA. Univ Maryland, Dept Physiol, Baltimore, MD 21201 USA. Univ Maryland, Program Neurosci, Baltimore, MD 21201 USA. RP Ruchkin, DS (reprint author), 4220 Wickford Rd, Baltimore, MD 21210 USA. EM ruchkind@ninds.nih.gov OI Grafman, Jordan H./0000-0001-8645-4457 FU NINDS NIH HHS [NS 11199] NR 55 TC 18 Z9 18 U1 0 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD NOV PY 2005 VL 42 IS 6 BP 643 EP 653 DI 10.1111/j.1469-8986.2005.00357.x PG 11 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 996HV UT WOS:000234165900003 PM 16364060 ER PT J AU Burg, MM Barefoot, J Berkman, L Catellier, DJ Czajkowski, S Saab, P Huber, M DeLillo, V Mitchell, P Skala, J Taylor, CB AF Burg, MM Barefoot, J Berkman, L Catellier, DJ Czajkowski, S Saab, P Huber, M DeLillo, V Mitchell, P Skala, J Taylor, CB CA ENRICHD Invest TI Low perceived social support and post-myocardial infarction prognosis in the enhancing recovery in coronary heart disease clinical trial: The effects of treatment SO PSYCHOSOMATIC MEDICINE LA English DT Article DE social support; acute coronary syndrome; clinical trials ID ACUTE MYOCARDIAL-INFARCTION; RISK-FACTOR; CARDIOVASCULAR-DISEASE; ARTERY DISEASE; FOLLOW-UP; MORTALITY; DEPRESSION; ENRICHD; MEN; INTERVENTION AB Objective: In post hoc analyses, to examine in low perceived social support (LPSS) patients enrolled in the Enhancing Recovery in Coronary Heart Disease (ENRICHD) clinical trial (n = 1503), the pattern of social support following myocardial infarction (MI), the impact of psychosocial intervention on perceived support, the relationship of perceived support at the time of MI to subsequent death and recurrent MI, and the relationship of change in perceived support 6 months after MI to subsequent mortality. Methods: Partner status (partner, no partner) and score (< 12 = low support; > 12 = moderate support) on the ENRICHD Social Support Instrument (ESSI) were used post hoc to define four levels of risk. The resulting 4 LPSS risk groups were compared on baseline characteristics, changes in social support, and medical outcomes to a group of concurrently enrolled acute myocardial infarction patients without depression or LPSS (MI comparison group, n = 408). Effects of treatment assignment on LPSS and death/recurrent MI were also examined. Results: All 4 LPSS risk groups demonstrated improvement in perceived support, regardless of treatment assignment, with a significant treatment effect only seen in the LPSS risk group with no partner and moderate support at baseline. During an average 29-month follow-up, the combined end point of death/nonfatal MI was 10% in the MI comparison group and 23% in the ENRICHD LPSS patients; LPSS conferred a greater risk in unadjusted and adjusted models (HR = 1.74-2.39). Change in ESSI score and/or improvement in perceived social support were not found to predict subsequent mortality. Conclusions: Baseline LPSS predicted death/recurrent MI in the ENRICHD cohort, independent of treatment assignment. Intervention effects indicated a partner surrogacy role for the interventionist and the need for a moderate level of support at baseline for the intervention to be effective. C1 Duke Univ, Dept Psychiat & Behav Sci, Durham, NC USA. Harvard Univ, Dept Soc Human Dev & Hlth, Cambridge, MA 02138 USA. Univ N Carolina, Sch Med, Dept Biostat, Chapel Hill, NC USA. NHLBI, Bethesda, MD 20892 USA. Univ Miami, Dept Psychol, Miami, FL 33152 USA. Univ Arkansas, Coll Publ Hlth, Little Rock, AR 72204 USA. Univ Washington, Sch Nursing, Seattle, WA 98195 USA. Washington Univ, Dept Psychiat, St Louis, MO 63110 USA. Stanford Univ, Dept Psychiat, Palo Alto, CA 94304 USA. RP Burg, MM (reprint author), Columbia Univ, Sch Med, 622 W 168 St,PH 9-941, New York, NY 10032 USA. EM mb2358@columbia.edu FU NHLBI NIH HHS [N01-HC-55144, N01-HC-55140, N01-HC-55141, N01-HC-55142, N01-HC-55143, N01-HC-55145, N01-HC-55146, N01-HC-55147, N01-HC-55148] NR 37 TC 65 Z9 65 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0033-3174 J9 PSYCHOSOM MED JI Psychosom. Med. PD NOV-DEC PY 2005 VL 67 IS 6 BP 879 EP 888 DI 10.1097/01.psy.0000188480.61949.8c PG 10 WC Psychiatry; Psychology; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 989QZ UT WOS:000233690100008 PM 16314592 ER PT J AU Cragg, GM Newman, DJ AF Cragg, GM Newman, DJ TI International collaboration in drug discovery and development from natural sources SO PURE AND APPLIED CHEMISTRY LA English DT Article; Proceedings Paper CT 9th International Chemistry Conference in Africa (ICCA-9) CY AUG 02-07, 2004 CL Arusha, TANZANIA SP African Assoc PUre & Appl Chem, Int Union Pure & Appl Chem DE biodiversity; drug discovery; drug development/costs and timeframes; multidisciplinary collaboration; international collaboration; benefit-sharing ID MOLLUSK ELYSIA-RUFESCENS; COMBINATORIAL LIBRARIES; PRIVILEGED STRUCTURES; ANCISTROCLADUS-KORUPENSIS; MULTIDRUG-RESISTANCE; CYTOTOXIC PEPTIDES; PHASE SYNTHESIS; HALICHONDRIN-B; SOLID-PHASE; BRYOPSIS SP AB Nature has been a source of medicinal agents for thousands of years, and an impressive number of modern drugs have been isolated froth natural sources, particularly plants, with many based on their use in traditional medicine. The past century, however, has seen an increasing role played by microorganisms in the production of the antibiotics and other drugs for the treatment of serious diseases, and more recently, marine organisms have proved to be a rich source of novel bioactive agents. Natural products will continue to play a crucial role in meeting this demand through the expanded investigation of the world's biodiversity, much of which remains unexplored. By using medicinal chemistry, and combinatorial chemical and biosynthetic technology, novel natural product leads will be optimized on the basis of their biological activities to yield effective chemotherapeutic and other bioactive agents. With much of the biological diversity found in tropical and subtropical regions, the investigation of these resources requires multidisciplinary international collaboration in the discovery and development process. Such collaboration can result in substantial short-term benefits accruing to source countries, with the potential for the generation of significant longer-term benefits in the select cases of those agents that proceed into advanced development, and possible commercialization. C1 NCI, Nat Prod Branch, Dev Therapeut Program, Fairview Ctr, Frederick, MD 21702 USA. RP Cragg, GM (reprint author), NCI, Nat Prod Branch, Dev Therapeut Program, Fairview Ctr, Suite 206,POB B, Frederick, MD 21702 USA. EM craggg@mail.nih.gov NR 68 TC 24 Z9 26 U1 0 U2 7 PU INT UNION PURE APPLIED CHEMISTRY PI RES TRIANGLE PK PA 104 TW ALEXANDER DR, PO BOX 13757, RES TRIANGLE PK, NC 27709-3757 USA SN 0033-4545 J9 PURE APPL CHEM JI Pure Appl. Chem. PD NOV PY 2005 VL 77 IS 11 BP 1923 EP 1942 DI 10.1351/pac200577111923 PG 20 WC Chemistry, Multidisciplinary SC Chemistry GA 988DQ UT WOS:000233572200011 ER PT J AU Kossenko, MM Thomas, TL Akleyev, AV Krestinina, LY Startsev, NV Vyushkova, OV Zhidkova, CM Hoffman, DA Preston, DL Davis, E Ron, E AF Kossenko, MM Thomas, TL Akleyev, AV Krestinina, LY Startsev, NV Vyushkova, OV Zhidkova, CM Hoffman, DA Preston, DL Davis, E Ron, E TI The Techa River cohort: Study design and follow-up methods SO RADIATION RESEARCH LA English DT Article ID ATOMIC-BOMB SURVIVORS; CANCER-MORTALITY; RADIATION-EXPOSURE; IONIZING-RADIATION; DOSIMETRY SYSTEM; RECONSTRUCTION; POPULATION; RISK; CONTAMINATION; FALLOUT AB Residents living on the banks of the Techa River in the Southern Urals region of Russia were exposed to radioactive contamination from the Mayak plutonium production and separation facility that discharged liquid radioactive waste into this river. This paper describes the methods used to establish and follow the Extended Techa River Cohort (ETRC), which includes almost 30,000 people living along the Techa River who were exposed to a complex mixture of radionuclides, largely Sr-90 and Cs-137. The system of regular follow-up allows ascertainment of vital status, cause of death and cancer incidence. With over 50 years of follow-up and over 50% deceased, the ETRC now provides a valuable opportunity to study a wide range of health effects, both early and late, associated with protracted internal and external radiation exposures. The wide range of doses allows analysis of the nature of the dose-response relationship based on internal comparisons. Other features of the cohort are the high proportion (40%) exposed under age 20, and the inclusion of both sexes. The limitations of the study include loss to follow-up due to difficulties in tracing some cohort members and migration and incomplete ascertainment of cause of death. (c) 2005 by Radiation Research Society. C1 Hirosoft Int Corp, Eureka, CA 95501 USA. Urals Res Ctr Radiat Med, Chelyabinsk, Russia. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. George Washington Univ, Washington, DC USA. Univ Illinois, Chicago, IL USA. RP Preston, DL (reprint author), Hirosoft Int Corp, 1335 H St, Eureka, CA 95501 USA. EM preston@hirosoft.net FU Intramural NIH HHS; NCI NIH HHS [N01-CP-11014] NR 29 TC 28 Z9 36 U1 0 U2 1 PU RADIATION RESEARCH SOC PI LAWRENCE PA 810 E TENTH STREET, LAWRENCE, KS 66044 USA SN 0033-7587 EI 1938-5404 J9 RADIAT RES JI Radiat. Res. PD NOV PY 2005 VL 164 IS 5 BP 591 EP 601 DI 10.1667/RR3451.1 PG 11 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 978ID UT WOS:000232865900001 PM 16238436 ER PT J AU Krestinina, LY Preston, DL Ostroumova, EV Degteva, MO Ron, E Vyushkova, OV Startsev, NV Kossenko, MM Akleyev, AV AF Krestinina, LY Preston, DL Ostroumova, EV Degteva, MO Ron, E Vyushkova, OV Startsev, NV Kossenko, MM Akleyev, AV TI Protracted radiation exposure and cancer mortality in the Techa River cohort SO RADIATION RESEARCH LA English DT Article ID ATOMIC-BOMB SURVIVORS; DOSIMETRY SYSTEM; DOSE RECONSTRUCTION; GENERAL MUTAGENS; HAZARD FUNCTION; RISK; POPULATION; WORKERS; MODEL; AGE AB In the 1950s many thousands of people living in rural villages on the Techa River received protracted internal and external exposures to ionizing radiation from the release of radioactive material from the Mayak plutonium production complex. The Extended Techa River Cohort includes 29,873 people born before 1950 who lived near the river sometime between 1950 and 1960. Vital status and cause of death are known for most cohort members. Individualized dose estimates have been computed using the Techa River Dosimetry System 2000. The analyses provide strong evidence of long-term carcinogenic effects of protracted low-dose-rate exposures; however, the risk estimates must be interpreted with caution because of uncertainties in the dose estimates. We provide preliminary radiation risk estimates for cancer mortality based on 1,842 solid cancer deaths (excluding bone cancer) and 61 deaths from leukemia. The excess relative risk per gray for solid cancer is 0.92 (95% CI 0.2; 1.7), while those for leukemia, including and excluding chronic lymphocytic leukemia, are 4.2 (CI 95% 1.2; 13) and 6.5 (CI 95% 1.8; 24), respectively. It is estimated that about 2.5% of the solid cancer deaths and 63% of the leukemia deaths are associated with the radiation exposure. (c) 2005 by Radiation Research Society. C1 Hirosoft Int Corp, Eureka, CA 95501 USA. Urals Res Ctr Radiat Med, Chelyabinsk, Russia. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Preston, DL (reprint author), Hirosoft Int Corp, 1335 H St, Eureka, CA 95501 USA. EM preston@hirosoft.net FU NCI NIH HHS [N01-CP11014] NR 40 TC 76 Z9 89 U1 0 U2 6 PU RADIATION RESEARCH SOC PI LAWRENCE PA 810 E TENTH STREET, LAWRENCE, KS 66044 USA SN 0033-7587 EI 1938-5404 J9 RADIAT RES JI Radiat. Res. PD NOV PY 2005 VL 164 IS 5 BP 602 EP 611 DI 10.1667/RR3452.1 PG 10 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 978ID UT WOS:000232865900002 PM 16238437 ER PT J AU Newkirk, MM Goldbach-Mansky, R Senior, BW Klippel, J Schumacher, HR El-Gabalawy, HS AF Newkirk, MM Goldbach-Mansky, R Senior, BW Klippel, J Schumacher, HR El-Gabalawy, HS TI Elevated levels of IgM and IgA antibodies to Proteus mirabilis and IgM antibodies to Escherichia coli are associated with early rheumatoid factor (RF)-positive rheumatoid arthritis SO RHEUMATOLOGY LA English DT Article DE Proteus antibodies; early synovitis; rheumatoid arthritis; rheumatoid factor; spondylarthritis ID TOLL-LIKE RECEPTORS; ANKYLOSING-SPONDYLITIS; ANTIPROTEUS ANTIBODIES; ENTEROBACTERIAL ANTIBODIES; RECENT-ONSET; B-CELLS; KLEBSIELLA; AUTOIMMUNITY; BACTERIA; LIPOPOLYSACCHARIDES AB Objective. Antibodies to Proteus mirabilis were previously detected in patients with established rheumatoid arthritis (RA). We examined the prevalence of antibodies to P. mirabilis and their associations with RA in early synovitis patients. Methods. Two hundred and forty-six patients with inflammatory arthritis for less than 1 yr were prospectively evaluated for 1 yr. Of these patients, 30% had rheumatoid factor (RF)-positive RA, 16% RF-negative RA, 17% a spondyloarthropathy and 37% undifferentiated arthritis. Serum antibodies to P. mirabilis, Escherichia coli and other potentially arthritogenic organisms (Chlamydia, Salmonella, Shigella, Campylobacter, Yersinia and parvovirus B19) and for antibodies specific for immunoglobulin (Ig) G damaged with advanced glycation end-products (anti-IgG-AGE) were measured. Results. IgM and IgA anti-Proteus antibodies were significantly higher in patients with RF-positive RA compared with all other patient groups (P < 0.0005 and P < 0.005). Anti-P. mirabilis IgG, and IgG, IgA, and IgM antibodies to other potentially arthritogenic pathogens did not differ in the patient groups. IgM antibodies to E. coli were elevated in RF-positive RA patients. Anti-P. mirabilis IgM and IgA results were not explained by false-positive reactions, because after absorption of RF there was no decrease in antibodies to Proteus in 10 of 12 patients. Proteus and E. coli antibodies were highest in patients positive for both RF and anti-IgG-AGE antibodies (P < 0.001). Patients with erosions tended to have higher IgA anti-Proteus titres, but no association with the shared HLA epitope or treatment was detected. Conclusion. Anti-P. mirabilis IgM and IgA and anti-E. coli IgM antibody elevations are associated with early seropositive RA and the presence of anti-IgG-AGE antibodies. The role that P. mirabilis or E. coli plays in early RF-positive RA requires further investigation. C1 McGill Univ, Ctr Hlth, Montreal, PQ H3G 1A4, Canada. NIAMSD, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. Univ Dundee, Dept Mol & Cellular Pathol, Dundee, Scotland. Arthrit Fdn, Atlanta, GA USA. Univ Penn, Philadelphia, PA 19104 USA. VA Med Ctr, Philadelphia, PA USA. Univ Manitoba, Div Rheumatol, Winnipeg, MB, Canada. RP Newkirk, MM (reprint author), McGill Univ, Ctr Hlth, 1650 Cedar Ave, Montreal, PQ H3G 1A4, Canada. EM Marianna.newkirk@mcgill.ca NR 41 TC 35 Z9 37 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-0324 J9 RHEUMATOLOGY JI RHEUMATOLOGY PD NOV PY 2005 VL 44 IS 11 BP 1433 EP 1441 DI 10.1093/rheumatology/kei036 PG 9 WC Rheumatology SC Rheumatology GA 978VK UT WOS:000232900900018 PM 16091399 ER PT J AU Artz, L Macaluso, M Meinzen-Derr, J Kelaghan, J Austin, H Fleenor, M Hook, EW Brill, I AF Artz, L Macaluso, M Meinzen-Derr, J Kelaghan, J Austin, H Fleenor, M Hook, EW Brill, I TI A randomized trial of clinician-delivered interventions promoting barrier contraception for sexually transmitted disease prevention SO SEXUALLY TRANSMITTED DISEASES LA English DT Article ID RISK-REDUCTION INTERVENTION; BLACK-ADOLESCENT WOMEN; CONDOM-USE INTENTIONS; PATIENT EDUCATION; HIV RISK; AIDS; ACQUISITION; EFFICACY; BEHAVIOR; STD AB Objective: The objective of this study was to compare 2 interventions promoting condoms and vaginal microbicides to prevent sexually transmitted disease (STD). Study: Women (N = 427) attending an STD clinic were randomly assigned to 2 clinician-delivered interventions and followed up monthly to assess condom/microbicide use and incidence of gonorrhea, chlamydia, and syphilis. Results: During follow up, condom use rates were 69 % (enhanced) and 49% (basic) and microbicide use rates were 44% and 29%, respectively. STD rates did not significantly differ between intervention groups. Perfect condom use (regardless of intervention arm) was associated with a 3-fold decrease in STD rates (relative risk [RR], 0.3; 95% confidence interval [CI], 0.1-0.8). Using a vaginal microbicide during >= 50% of the acts of intercourse was associated with reduced STD rates (RR, 0.5; 95% CI, 0.3-1.0) across intervention groups and condom use categories. Conclusions: The enhanced intervention increased use of condoms and vaginal microbicide; however, STD rates did not decrease because a protective effect was seen only among perfect barrier users, and the enhanced intervention only modestly increased perfect use. C1 Univ Alabama, Sch Publ Hlth, Dept Epidemiol & Int Hlth, Birmingham, AL 35294 USA. Univ Alabama, Sch Med, Dept Med, Div Infect Dis, Birmingham, AL 35294 USA. NICHHD, Contracept & Reprod Evaluat Branch, Bethesda, MD 20892 USA. Emory Univ, Rollins Sch Publ Hlth, Dept Epidemiol, Atlanta, GA 30322 USA. Jefferson Cty Dept Hlth, Birmingham, AL USA. RP Macaluso, M (reprint author), CDC, Div Reprod Hlth, NCCDPHP, 470 Buford Highway,Mail Stop K-34, Atlanta, GA 30341 USA. EM mmacaluso@cdc.gov RI Macaluso, Maurizio/J-2076-2015; Meinzen-Derr, Jareen/N-4805-2015 OI Macaluso, Maurizio/0000-0002-2977-9690; NR 35 TC 14 Z9 14 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0148-5717 J9 SEX TRANSM DIS JI Sex. Transm. Dis. PD NOV PY 2005 VL 32 IS 11 BP 672 EP 679 DI 10.1097/01.olq.0000175404.18098.dd PG 8 WC Infectious Diseases SC Infectious Diseases GA 983VH UT WOS:000233259700005 PM 16254541 ER PT J AU Heflin, CM Siefert, K Williams, DR AF Heflin, CM Siefert, K Williams, DR TI Food insufficiency and women's mental health: Findings from a 3-year panel of welfare recipients SO SOCIAL SCIENCE & MEDICINE LA English DT Article DE food insufficiency; food security; low-income women; mental health; depression; USA ID NUTRITION EXAMINATION SURVEY; UNITED-STATES; PRIMARY-CARE; PSYCHOLOGICAL DISTRESS; PSYCHIATRIC-DISORDERS; MAJOR DEPRESSION; NATIONAL-HEALTH; SELF-ESTEEM; MOTHERS; INSECURITY AB Household food insufficiency is a significant problem in the United States, and has been associated with poor outcomes on mental health indicators among low-income women. However, it is difficult to disentangle the mental health consequences of household food insufficiency from poverty and other shared risk factors. Drawing on theories of the social production of health and disease, research evidence linking food insufficiency with poor mental health, and high rates of food insufficiency among welfare recipients, we examined whether a change in household food insufficiency is associated with a change in women's self-reported mental health in a sample of current and recent welfare recipients over a 3-year period of time, controlling for common risk factors. Data were obtained from a prospective survey of women who were welfare recipients in an urban Michigan county in February 1997 (n = 753). We estimated fixed effect models for changes in mental health status that make use of information on household food insufficiency gathered in the fall of 1997, 1998, and 1999. The relationship between household food insufficiency and respondents' meeting the diagnostic screening criteria for major depression remained highly significant even when controlling for factors known to confer increased risk of depression and time invariant unobserved heterogeneity. These findings add to growing evidence that household food insufficiency has potentially serious consequences for low-income women's mental health. If confirmed by further research, they suggest that the public health burden of depression in welfare recipients and other low-income women could be reduced by policy-level interventions to reduce their exposure to household food insufficiency. (c) 2005 Elsevier Ltd. All rights reserved. C1 Univ Kentucky, Martin Sch Publ Policy, Lexington, KY 40503 USA. Univ Michigan, NIMH, Res Ctr Poverty Risk & Mental Hlth, Ann Arbor, MI 48109 USA. Univ Michigan, Inst Social Res, Ann Arbor, MI 48106 USA. RP Heflin, CM (reprint author), Univ Kentucky, Martin Sch Publ Policy, 429 POT, Lexington, KY 40503 USA. EM cmh@uky.edu; ksiefert@umich.edu; wildavid@umich.edu RI Rishbeth, Clare /H-2151-2011 FU NIMH NIH HHS [R24-MH51361] NR 94 TC 125 Z9 125 U1 5 U2 26 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0277-9536 J9 SOC SCI MED JI Soc. Sci. Med. PD NOV PY 2005 VL 61 IS 9 BP 1971 EP 1982 DI 10.1016/j.socscimed.2005.04.014 PG 12 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 967AM UT WOS:000232063900010 PM 15927331 ER PT J AU Holohan, TV Colestro, J Grippi, J Converse, J Hughes, M AF Holohan, TV Colestro, J Grippi, J Converse, J Hughes, M TI Analysis of diagnostic error in paid malpractice claims with substandard care in a large healthcare system SO SOUTHERN MEDICAL JOURNAL LA English DT Article DE adverse event; diagnostic error; legal; liability; malpractice; medical error; National Practitioner Data Bank ID ADVERSE EVENTS; HOSPITALIZED-PATIENTS; NEGLIGENT CARE; COLORADO; QUALITY; UTAH AB Objective: Although claims databases are not representative of all care delivery, their predisposition toward serious unintended injury can complement resource-intensive chart reviews and guide patient safety initiatives. Materials and Methods: Non-Veterans Health Administration (VA) practitioners reviewed 1,949 VA malpractice claims paid during fiscal years 1998 through 2003. The portion associated with substandard care, the severity of harm, and types of negligence were identified. Results: Negligent adverse events occurred in 37% (n = 723) of paid VA malpractice claims. These had high proportions of serious injury (55%) and morbidity (37%). Diagnostic negligent adverse events were most frequent (45%) and with 41% associated morbidity. The annual incidence of diagnosis-related paid VA malpractice claims was 1.95 per 100,000 patients and predicts that 122 of every 100,000 patients may have diagnostic negligent adverse events. Comparisons against non-VA data suggest this to be a healthcare industry problem. Conclusions: Diagnosis-related negligent adverse events are a serious problem in the healthcare industry. C1 NIH, Bethesda, MD 20892 USA. Vet Hlth Adm, Buffalo, NY USA. Vet Hlth Adm Cent Off, Washington, DC USA. RP Grippi, J (reprint author), Buffalo VA Med Ctr, 3495 Bailey Ave, Buffalo, NY 14215 USA. EM john.grippi@med.va.gov NR 16 TC 16 Z9 16 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0038-4348 J9 SOUTH MED J JI South.Med.J. PD NOV PY 2005 VL 98 IS 11 BP 1083 EP 1087 DI 10.1097/01.smj.0000170729.51651.f7 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 991JX UT WOS:000233811400010 PM 16351028 ER PT J AU Noaksson, K Zoric, N Zeng, XM Rao, MS Hyllner, J Semb, H Kubista, M Sartipy, P AF Noaksson, K Zoric, N Zeng, XM Rao, MS Hyllner, J Semb, H Kubista, M Sartipy, P TI Monitoring differentiation of human embryonic stem cells using real-time PCR SO STEM CELLS LA English DT Article DE human embryonic stem cell; differentiation; real-time polymerase chain reaction; gene expression ID PROLONGED UNDIFFERENTIATED GROWTH; GENE-EXPRESSION; MOLECULAR SIGNATURE; HUMAN BLASTOCYSTS; HUMAN FEEDERS; ES CELLS; LINES; CULTURE; MOUSE; PLURIPOTENCY AB There is a general lack of rapid, sensitive, and quantitative methods for the detection of differentiating human embryonic stem cells (hESCs). Using light microscopy and immunohistochemistry, we observed that morphological changes of differentiating hESCs precede any major alterations in the expression of several commonly used hESC markers (SSEA-3, SSEA-4, TRA-1-60, TRA-1-81, Oct-4, and Nanog). In an attempt to quantify the changes during stochastic differentiation of hESCs, we developed a robust and sensitive multimarker quantitative real-time polymerase chain reaction (QPCR) method. To maximize the sensitivity of the method, we measured the expression of up- and downregulated genes before and after differentiation of the hESCs. Out of the 12 genes assayed, we found it clearly sufficient to determine the relative differentiation state of the cells by calculating a collective expression index based on the mRNA levels of Oct-4, Nanog, Cripto, and (x-fetoprotein. We evaluated the method using different hESC lines maintained in either feeder-dependent or feeder-free culture conditions. The QPCR method is very flexible, and by appropriately selecting reporter genes, the method can be designed for various applications. The combination of QPCR with hESC-based technologies opens novel avenues for high-throughput analysis of hESCs in, for example, pharmacological and cytotoxicity screening. STEM CELLS 2005;23:1460-1467. C1 Cellartis AB, S-41346 Gothenburg, Sweden. TATAA Bioctr, Lundberg Lab, Gothenburg, Sweden. Natl Inst Drug Abuse, Cellular Neurobiol Branch, Dept Hlth & Human Serv, Baltimore, MD USA. NIA, Neurosci Lab, Dept Hlth & Human Serv, Baltimore, MD 21224 USA. Lund Univ, Endocrinol Sect, Lund, Sweden. RP Sartipy, P (reprint author), Cellartis AB, Arvid Wallgens Backe 20, S-41346 Gothenburg, Sweden. EM peter.sartipy@cellartis.com RI Kubista, Mikael/A-5689-2008 OI Kubista, Mikael/0000-0002-2940-352X FU Intramural NIH HHS; NCRR NIH HHS [R24RR019514-01] NR 37 TC 45 Z9 47 U1 0 U2 6 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1066-5099 J9 STEM CELLS JI Stem Cells PD NOV-DEC PY 2005 VL 23 IS 10 BP 1460 EP 1467 DI 10.1634/stemcells.2005-0093 PG 8 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Oncology; Cell Biology; Hematology SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology GA 989XZ UT WOS:000233708700005 PM 16081663 ER PT J AU Beard, WA Wilson, SH AF Beard, WA Wilson, SH TI Syn-full behavior by T7 DNA polymerese SO STRUCTURE LA English DT Editorial Material ID FIDELITY; REPLICATION; INSERTION; INSIGHTS; BETA C1 Natl Inst Environm Hlth Sci, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Beard, WA (reprint author), Natl Inst Environm Hlth Sci, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. NR 10 TC 1 Z9 1 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0969-2126 J9 STRUCTURE JI Structure PD NOV PY 2005 VL 13 IS 11 BP 1580 EP 1582 DI 10.1016/j.str.2005.10.003 PG 3 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 986LT UT WOS:000233451800002 PM 16271879 ER PT J AU Brieba, LG Kokoska, RJ Bebenek, K Kunkel, TA Ellenberger, T AF Brieba, LG Kokoska, RJ Bebenek, K Kunkel, TA Ellenberger, T TI A lysine residue in the fingers subdomain of T7 DNA polymerase modulates the miscoding potential of 8-oxo-7,8-dihydroguanosine SO STRUCTURE LA English DT Article ID STATE KINETIC-ANALYSIS; NUCLEOTIDE INSERTION; STEADY-STATE; REPLICATION FIDELITY; O-HELIX; OXIDATIVE DAMAGE; GAMMA; BETA; BACTERIOPHAGE-T7; CONFORMATION AB 8-Oxo-7,8-dihydroguanosine (8oG) is a highly mutagenic DNA lesion that stably pairs with adenosine, forming 8oG(syn)(.)dA(antt) Hoogsteen base pairs. DNA polymerases show different propensities to insert dCMP or dAMP opposite 8oG, but the molecular mechanisms that determine faithful or mutagenic bypass are poorly understood. Here, we report kinetic and structural data providing evidence that, in T7 DNA polymerase, residue Lys536 is responsible for attenuating the miscoding potential of 8oG. The Lys536AIa polymerase shows a significant increase in mutagenic 8oG bypass versus wild-type polymerase, and a crystal structure of the Lys536A1a mutant reveals a closed complex with an 8oG(syn).dATP mismatch in the polymerase active site, in contrast to the unproductive, open complex previously obtained by using wild-type polymerase. We propose that Lys536 acts as a steric and/or electrostatic filter that attenuates the miscoding potential of 8oG by normally interfering with the binding of 8oG in a syn conformation that pairs with dATP. C1 Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Natl Inst Environm Hlth Scu, Mol Genet Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC USA. Natl Inst Environm Hlth Scu, Struct Biol Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC USA. RP Ellenberger, T (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, 240 Longwood Ave, Boston, MA 02115 USA. EM tome@hms.harvard.edu RI Brieba, Luis/I-8447-2016 OI Brieba, Luis/0000-0002-6073-5207 FU Intramural NIH HHS; NIGMS NIH HHS [GM55390] NR 41 TC 32 Z9 32 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0969-2126 J9 STRUCTURE JI Structure PD NOV PY 2005 VL 13 IS 11 BP 1653 EP 1659 DI 10.1016/j.str.2005.07.020 PG 7 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 986LT UT WOS:000233451800011 PM 16271888 ER PT J AU Aue, G Horne, MK AF Aue, G Horne, MK TI Clinical significance of hypodysfibrinogenemia gamma 326 Cys -> Tyr? SO THROMBOSIS AND HAEMOSTASIS LA English DT Letter ID FIBRINOGEN; PLASMA; VII C1 NIH, Dept Lab Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. NHLBI, Hematol Branch, Bethesda, MD 20892 USA. RP Horne, MK (reprint author), NIH, Dept Lab Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. EM mhorne@mail.cc.nih.gov NR 6 TC 0 Z9 0 U1 0 U2 0 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD NOV PY 2005 VL 94 IS 5 BP 1108 EP 1109 PG 2 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 985LB UT WOS:000233377900034 PM 16363258 ER PT J AU Mentuccia, D Thomas, MJ Coppotelli, G Reinhart, LJ Mitchell, BD Shuldiner, AR Celi, FS AF Mentuccia, D Thomas, MJ Coppotelli, G Reinhart, LJ Mitchell, BD Shuldiner, AR Celi, FS TI The Thr92Ala deiodinase type 2 (DIO2) variant is not associated with type 2 diabetes or indices of insulin resistance in the Old Order of Amish SO THYROID LA English DT Article; Proceedings Paper CT 86th Annual Meeting of the Endocrine-Society CY JUN 12-15, 2004 CL New Orleans, LA SP Endocrine Soc ID IODOTHYRONINE DEIODINASE; PEDIGREES; RECEPTOR; ROLES AB A common polymorphism of the type 2 deiodinase gene (Thr92Ala DIO2) was found to be associated with insulin resistance in a mixed Caucasian population. The aim of this study was to investigate the association of the Thr92Ala DIO2 variant to indices of insulin resistance in the Old Order Amish. A genotype-phenotype association study was performed at the research clinic in Strasburg, Pennsylvania, and the molecular genetics laboratory at the University of Maryland, Baltimore, Maryland, and the National Institutes of Health, Bethesda, Maryland. A total of 1,268 subjects participated in the Amish Family Diabetes Study. An association among the Thr92Ala DIO2 variant and type 2 diabetes, indices of insulin resistance (HOMA-IR), insulin secretion, free thyroid hormones, and thyrotropin (TSH) was found. No association was found among the Thr92Ala DIO2 variant and type 2 diabetes, impaired glucose tolerance, or body mass index (BMI) in the Amish. In nondiabetics (n = 747), the Ala92 allele tended to be associated with decreased rather then increased insulin secretion. No differences were observed in thyroid hormones or TSH. Contrary to prior findings, the Thr92Ala DIO2 variant tends to be associated with increased rather then decreased insulin sensitivity in the Amish. These findings could be secondary to a different genetic background or to environmental factors specific for this population. C1 NIDDK, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Univ Roma Tor Vergata, Dept Med, Div Endocrinol, Rome, Italy. Univ Maryland, Dept Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA. Vet Adm Med Ctr, Geriatr Res & Educ Clin Ctr, Baltimore, MD USA. RP Mentuccia, D (reprint author), NIDDK, Clin Endocrinol Branch, NIH, Bldg 10,CRC,Room 6-3950,10 Ctr Dr,MSC 1613, Bethesda, MD 20892 USA. OI Mitchell, Braxton/0000-0003-4920-4744 FU NIDDK NIH HHS [R01 DK54261] NR 22 TC 24 Z9 24 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1050-7256 J9 THYROID JI Thyroid PD NOV PY 2005 VL 15 IS 11 BP 1223 EP 1227 DI 10.1089/thy.2005.15.1223 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 996DZ UT WOS:000234155900001 PM 16356084 ER PT J AU Tronko, M Kravchenko, V Fink, D Hatch, M Turchin, V McConnell, R Shpak, V Brenner, A Robbins, J Lusanchuk, I Howe, G AF Tronko, M Kravchenko, V Fink, D Hatch, M Turchin, V McConnell, R Shpak, V Brenner, A Robbins, J Lusanchuk, I Howe, G TI Iodine excretion in regions of Ukraine affected by the Chornobyl accident: Experience of the Ukrainian-American Cohort Study of Thyroid Cancer and Other Thyroid Diseases SO THYROID LA English DT Article ID RISK; DEFICIENCY; EXPOSURE; CHILDREN AB Urinary iodine concentrations were measured in 11,926 subjects who are participants in the Ukrainian-American Cohort Study of Thyroid Cancer and Other Thyroid Diseases Following the Chornobyl Accident. Measurements were made in two time periods corresponding to the first and second thyroid screening cycles (1998-2000, 2001-2003). These time periods fall before and after initiation of a government program to increase iodine sufficiency. Median urinary iodine concentrations did increase in the later time period compared to the earlier [47.5 mu g/L, 95% confidence interval (CI) 46.5-48.9 mu g/L versus 41.7 mu g/L, 95% CI 40.4-42.5 mu g/L], but levels remained in the mild-to-moderate iodine deficiency range as defined by the World Health Organization (WHO), indicating the need for further efforts at iodination. In both time periods, urinary iodine levels were found to vary by place of residence and were lower in rural compared to urban areas. Iodine status needs to be considered when evaluating risk of thyroid cancer and other thyroid diseases. C1 NCI, Radiat Epidemiol Branch, DHHS, NIH, Rockville, MD 20852 USA. Ukraine Acad Med Sci, Inst Endocrinol & Metab, Kiev, Ukraine. Columbia Univ, New York, NY USA. NIDDK, NIH, Bethesda, MD USA. RP Tronko, M (reprint author), NCI, Radiat Epidemiol Branch, DHHS, NIH, 6120 Execut Blvd, Rockville, MD 20852 USA. NR 18 TC 19 Z9 19 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1050-7256 J9 THYROID JI Thyroid PD NOV PY 2005 VL 15 IS 11 BP 1291 EP 1297 DI 10.1089/thy.2005.15.1291 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 996DZ UT WOS:000234155900012 PM 16356095 ER PT J AU Allen, S Read, S DiPaolo, R McHugh, RS Shevach, EM Gleeson, PA Van Driel, IR AF Allen, S Read, S DiPaolo, R McHugh, RS Shevach, EM Gleeson, PA Van Driel, IR TI Peripheral rather than thymic events are important in establishing tolerance to gastric autoantigens SO TISSUE ANTIGENS LA English DT Meeting Abstract CT 35th Annual SCientific Meeting of the Australasian-Society-for-Immunology/14th International HLA and Immunogenetics Workshops CY NOV 29-DEC 02, 2005 CL Melbourne, AUSTRALIA SP Australasian Soc Immunol C1 Univ Melbourne, Parkville, Vic 3052, Australia. NIAID, NIH, Cellular Immunol Sect, Immunol Lab, Bethesda, MD 20892 USA. Miltenyi Biotec Inc, Auburn, CA 95602 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0001-2815 J9 TISSUE ANTIGENS JI Tissue Antigens PD NOV PY 2005 VL 66 IS 5 MA 8 BP 345 EP 345 PG 1 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA 987UL UT WOS:000233542700010 ER PT J AU Andoniou, CE Van Dommelen, SLH Voigt, V Andrews, DM Brizard, G Asselin-Paturel, C Delale, T Stacey, KJ Trinchieri, G Degli-Esposti, MA AF Andoniou, CE Van Dommelen, SLH Voigt, V Andrews, DM Brizard, G Asselin-Paturel, C Delale, T Stacey, KJ Trinchieri, G Degli-Esposti, MA TI Beyond plasmacytoid dendritic cells: Conventional CD11b(+) DCs efficiently prime NK cell responses to murine cytomegalovirus SO TISSUE ANTIGENS LA English DT Meeting Abstract CT 35th Annual SCientific Meeting of the Australasian-Society-for-Immunology/14th International HLA and Immunogenetics Workshops CY NOV 29-DEC 02, 2005 CL Melbourne, AUSTRALIA SP Australasian Soc Immunol C1 Lions Eye Inst, Nedlands, WA, Australia. Univ Western Australia, Immunol & Virol Program, Ctr Ophthalmol & Visual Sci, Crawley, WA, Australia. Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. Schering Plough Corp, Lab Immunol Res, Dardilly, France. Univ Queensland, Inst Mol Biosci, Cooperat Res Ctr Chron Infl, Brisbane, Qld, Australia. NIAID, Lab Parasit Dis, Bethesda, MD 20892 USA. RI Degli-Esposti, Mariapia/E-9529-2013; Degli-Esposti, Mariapia/H-9073-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0001-2815 J9 TISSUE ANTIGENS JI Tissue Antigens PD NOV PY 2005 VL 66 IS 5 MA 16 BP 348 EP 348 PG 1 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA 987UL UT WOS:000233542700018 ER PT J AU Feolo, M Mickelson, E Helmberg, W Hoffman, D Pei, J Nisperos, C Schoch, G Hansen, JA AF Feolo, M Mickelson, E Helmberg, W Hoffman, D Pei, J Nisperos, C Schoch, G Hansen, JA TI The international histocompatibility working group (IHWG) human MHC reference panels: Public access to HLA genotype and haplotype data through the DBMHC SO TISSUE ANTIGENS LA English DT Meeting Abstract CT 35th Annual SCientific Meeting of the Australasian-Society-for-Immunology/14th International HLA and Immunogenetics Workshops CY NOV 29-DEC 02, 2005 CL Melbourne, AUSTRALIA SP Australasian Soc Immunol C1 Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. Dept Blutgrp Serol & Transfus Med, Graz, Austria. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0001-2815 J9 TISSUE ANTIGENS JI Tissue Antigens PD NOV PY 2005 VL 66 IS 5 MA 194 BP 413 EP 413 PG 1 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA 987UL UT WOS:000233542700196 ER PT J AU Gao, X Bashirova, A Iversen, AN Phair, J Goedert, JJ Buchbinder, S Hoots, K Vlahov, D Altfeld, M O'Brien, SJ Carrington, M AF Gao, X Bashirova, A Iversen, AN Phair, J Goedert, JJ Buchbinder, S Hoots, K Vlahov, D Altfeld, M O'Brien, SJ Carrington, M TI AIDS restriction HLA allotypes target distinct intervals of HIV-1 pathogenesis SO TISSUE ANTIGENS LA English DT Meeting Abstract CT 35th Annual SCientific Meeting of the Australasian-Society-for-Immunology/14th International HLA and Immunogenetics Workshops CY NOV 29-DEC 02, 2005 CL Melbourne, AUSTRALIA SP Australasian Soc Immunol C1 SAIC FREdrick Inc, Basic Res Program, Frederick, MD 60611 USA. Consolidated Safety Serv Inc, Fairfax, VA 60611 USA. Univ Oxford, Weatherall Inst Mol Med, MRC Human Immunol Unit, Oxford, 20892, England. Northwestern Univ, Howard Brown Hlth Ctr, Chicago, IL USA. Northwestern Univ, Fineberg Sch Med, Chicago, IL USA. NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD USA. San Francisco Dept Publ Hlth, San Francisco, CA USA. Univ Texas, Hlth Sci Ctr, Gulf States Hemophilia Ctr, Houston, TX USA. New York Acad Med, Ctr Urban Epidemiol Studies, New York, NY USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA USA. Natl Canc Inst, Lab Genom Divers, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0001-2815 J9 TISSUE ANTIGENS JI Tissue Antigens PD NOV PY 2005 VL 66 IS 5 MA 223 BP 424 EP 424 PG 1 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA 987UL UT WOS:000233542700225 ER PT J AU Liu, Z Tebbutt, N Lee, F Cavicchiolo, T Gill, S Poon, AMT Hopkins, W Smyth, FE Murone, C MacGregor, D Papenfuss, A Chappell, B Saunder, TH Brechbiel, NW Davis, ID Murphy, R Chong, G Stockert, E Ritter, G AF Liu, Z Tebbutt, N Lee, F Cavicchiolo, T Gill, S Poon, AMT Hopkins, W Smyth, FE Murone, C MacGregor, D Papenfuss, A Chappell, B Saunder, TH Brechbiel, NW Davis, ID Murphy, R Chong, G Stockert, E Ritter, G TI Pharmacokinetics and biodistribution of humanized monoclonal antibody hu3S193 in a phase I trial of patients with advanced epithelial cancers which express the Lewis-gamma antigen SO TISSUE ANTIGENS LA English DT Meeting Abstract CT 35th Annual SCientific Meeting of the Australasian-Society-for-Immunology/14th International HLA and Immunogenetics Workshops CY NOV 29-DEC 02, 2005 CL Melbourne, AUSTRALIA SP Australasian Soc Immunol C1 Ludwig Inst Canc Res, Melbourne Tumour Biol Branch, Heidelberg, Vic, Australia. Austin Hosp, Ctr PET, Heidelberg, Vic 3084, Australia. Austin Hosp, Canc Clin Trial Ctr, Heidelberg, Vic 3084, Australia. Austin Hosp, Heidelberg, Vic 3084, Australia. NIH, Radioimmune & Inorgan Chem Sect, Bethesda, MD 20892 USA. Ludwig Inst Canc Res, New York Branch, New York, NY USA. RI Davis, Ian/A-1430-2012; Papenfuss, Anthony/C-6297-2008 OI Davis, Ian/0000-0002-9066-8244; Papenfuss, Anthony/0000-0002-1102-8506 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0001-2815 J9 TISSUE ANTIGENS JI Tissue Antigens PD NOV PY 2005 VL 66 IS 5 MA 377 BP 481 EP 481 PG 1 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA 987UL UT WOS:000233542700378 ER PT J AU Sanders, MT Tai, TY Bennink, J Yewdell, J Chen, W AF Sanders, MT Tai, TY Bennink, J Yewdell, J Chen, W TI Empty H-2K(k) MHC class I molecules are retained in the ER by the peptide loading complex SO TISSUE ANTIGENS LA English DT Meeting Abstract CT 35th Annual SCientific Meeting of the Australasian-Society-for-Immunology/14th International HLA and Immunogenetics Workshops CY NOV 29-DEC 02, 2005 CL Melbourne, AUSTRALIA SP Australasian Soc Immunol C1 Ludwig Inst Canc Res Austin Hlth, T Cell Lab, Heidelberg, Vic, Australia. NIAID, Viral Dis Lab, Bethesda, MD 20892 USA. RI yewdell, jyewdell@nih.gov/A-1702-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0001-2815 J9 TISSUE ANTIGENS JI Tissue Antigens PD NOV PY 2005 VL 66 IS 5 MA 518 BP 532 EP 532 PG 1 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA 987UL UT WOS:000233542700519 ER PT J AU Van Bockel, D Suzuki, K Warton, K Ammaranond, P Douek, D La Gruta, N Munier, M McGinley, C Nallaiah, K Stanley, K Turner, SJ Zaunders, J Cooper, DA Kelleher, AD AF Van Bockel, D Suzuki, K Warton, K Ammaranond, P Douek, D La Gruta, N Munier, M McGinley, C Nallaiah, K Stanley, K Turner, SJ Zaunders, J Cooper, DA Kelleher, AD TI TCR clonotypic analysis of CMV antigen-specific CD8+ T-cells from formaldehyde fixed peripheral blood SO TISSUE ANTIGENS LA English DT Meeting Abstract CT 35th Annual SCientific Meeting of the Australasian-Society-for-Immunology/14th International HLA and Immunogenetics Workshops CY NOV 29-DEC 02, 2005 CL Melbourne, AUSTRALIA SP Australasian Soc Immunol C1 St Vincents Hosp, Ctr Immunol, HIV Immunovirol Grp, Sydney, NSW, Australia. Univ New S Wales, Natl Ctr HIV Epidemiol & Clin Res, Sydney, NSW, Australia. Corbett Res Pty Ltd, Ctr Immunol, Sydney, NSW, Australia. Univ Melbourne, Dept Microbiol & Immunol, Melbourne, Vic, Australia. Natl Inst Hlth, Vaccine Res Ctr, Bethesda, MD USA. RI Zaunders, John/J-6553-2012 OI Zaunders, John/0000-0002-5912-5989 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0001-2815 J9 TISSUE ANTIGENS JI Tissue Antigens PD NOV PY 2005 VL 66 IS 5 MA 628 BP 573 EP 574 PG 2 WC Cell Biology; Immunology; Pathology SC Cell Biology; Immunology; Pathology GA 987UL UT WOS:000233542700629 ER PT J AU Holsapple, MP Farland, WH Landry, TD Monteiro-Riviere, NA Carter, JM Walker, NJ Thomas, KV AF Holsapple, MP Farland, WH Landry, TD Monteiro-Riviere, NA Carter, JM Walker, NJ Thomas, KV TI Research strategies for safety evaluation of nanomaterials, part II: Toxicological and safety evaluation of nanomaterials, current challenges and data needs SO TOXICOLOGICAL SCIENCES LA English DT Editorial Material DE nanomaterials; nanoscale materials; nanotechnology; risk assessment; toxicology ID ULTRAFINE PARTICLES; TITANIUM-DIOXIDE; PULMONARY RESPONSES; RESPIRATORY-TRACT; INHALED ULTRAFINE; OXIDATIVE STRESS; OXIDE PARTICLES; LUNG INJURY; ZINC-OXIDE; RAT LUNG AB This article summarizes a roundtable discussion held at the 2005 Society of Toxicology Annual Meeting in New Orleans, LA. The purpose of the roundtable was to review the current challenges and data needs for conducting toxicological and safety evaluations for nanomaterials, with the goals of presenting the current state-of-the science on the safety of nanomaterials and bringing together scientists representing government, academia, and industry to identify priorities for developing data to facilitate risk assessments for these materials. In this summary, the unique physicochemical properties associated with nanomaterials are reviewed in the context of the difficulties associated with measuring and characterizing them. In addition, the development of appropriate hazard data, the collection of accurate human and environmental exposure information, and the development of a better fundamental understanding of the modes of action for nanomaterials are discussed as factors that will impact the development of comprehensive toxicological and safety evaluations. C1 ILSI Hlth & Environm Sci Inst, Washington, DC 20005 USA. US EPA, Off Res & Dev, Washington, DC 20460 USA. Dow Chem Co USA, Toxicol & Environm Res & Consulting, Midland, MI 48674 USA. N Carolina State Univ, Ctr Chem Toxicol Res & Pharmacokinet, Raleigh, NC 27606 USA. Procter & Gamble Co, Miami Valley Labs, Cent Prod Safety, Cincinnati, OH 45253 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Thomas, KV (reprint author), ILSI Hlth & Environm Sci Inst, 1 Thomas Circle NW,9th Floor, Washington, DC 20005 USA. EM kthomas@ilsi.org RI Walker, Nigel/D-6583-2012 OI Walker, Nigel/0000-0002-9111-6855 NR 36 TC 113 Z9 126 U1 1 U2 23 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD NOV PY 2005 VL 88 IS 1 BP 12 EP 17 DI 10.1093/toxsci/kfi293 PG 6 WC Toxicology SC Toxicology GA 972BH UT WOS:000232428300003 PM 16120754 ER PT J AU Sanders, JM Burka, LT Smith, CS Black, W James, R Cunningham, ML AF Sanders, JM Burka, LT Smith, CS Black, W James, R Cunningham, ML TI Differential expression of CYP1A, 2B, and 3A genes in the F344 rat following exposure to a polybrominated diphenyl ether mixture or individual components SO TOXICOLOGICAL SCIENCES LA English DT Article DE polybrominated diphenyl ethers; polybrominated dibenzodioxins and dibenzofurans; polychlorinated biphenyls; persistent organic compounds; gene expression; quantitative RT-PCR ID POLYCHLORINATED-BIPHENYLS PCBS; BROMINATED FLAME RETARDANTS; RISK-ASSESSMENT; MECHANISTIC CONSIDERATIONS; HYDROCARBON RECEPTOR; BRAIN-DEVELOPMENT; ENZYME-INDUCTION; DIBENZOFURANS; TIME; CYTOCHROME-P-450 AB Polybrominated diphenyl ethers (PBDEs), used as flame retardants, have been detected in the environment and in mammalian tissues and fluids. Evidence indicates that PBDE mixtures induce CYPs through aryl hydrocarbon receptor (AhR)-dependent and -independent pathways. The present work has investigated the effects of individual components of a commercial PBDE mixture (DE71) on expression of CYP1A1, a biomarker for activation of the AhR (dioxin-like), and CYP2B and CYP3A, biomarkers for activation of the constitutive androstane and pregnanexreceptors (CAR and PXR), respectively, in the rat. Male F344 rats were dosed orally on three consecutive days with either DE71, PBDE components, 2,2',4,4'-tetraBDE (BDE47), 2,2',4,4',5-pentaBDE (BDE99), 2,2',4,4',5,5'-hexaBDE (BDE153), representative polybrominated dibenzofurans (PBDFs) present in DE71, or reference PCBs. Differential expression of target genes was determined in liver 24 h after the last dose. Quantitative PCR analysis indicated up-regulation of CYP1A1 by DE71; however, the response was weak compared to that for dioxin-like PCB126. Individual PBDE components of DE71 up-regulated CYP1A1 only at the highest administered dose (100 mu mol/kg/day). Representative PBDFs efficiently up-regulated CYP1A1; therefore, they, along with other PBDFs and polybrominated dibenzodioxins detected in DE71 and individual PBDE components, may be responsible for most, if not all, dioxin-like properties previously observed for PBDEs. Conversely, PBDEs appear capable of up-regulating CYP2B and CYP3A in rats at doses similar to that for non-dioxin-like PCB153. These results indicate that in vivo PBDE-mediated toxicity would be better categorized by AhR-independent mechanisms, rather than the well-characterized AhR-dependent mechanism associated with exposure to dioxin-like chemicals. C1 NIEHS, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. N Carolina State Univ, Dept Toxicol, Raleigh, NC 27695 USA. Battelle Mem Inst, Columbus, OH 43201 USA. RP Sanders, JM (reprint author), NIEHS, Lab Pharmacol & Chem, POB 12233, Res Triangle Pk, NC 27709 USA. EM sander10@niehs.nih.gov NR 40 TC 93 Z9 98 U1 2 U2 27 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD NOV PY 2005 VL 88 IS 1 BP 127 EP 133 DI 10.1093/toxsci/kfi288 PG 7 WC Toxicology SC Toxicology GA 972BH UT WOS:000232428300015 PM 16107549 ER PT J AU Eskelinen, EL Cuervo, AM Taylor, MRG Nishino, I Blum, JS Dice, JF Sandoval, IV Lippincott-Schwartz, J August, JT Saftig, P AF Eskelinen, EL Cuervo, AM Taylor, MRG Nishino, I Blum, JS Dice, JF Sandoval, IV Lippincott-Schwartz, J August, JT Saftig, P TI Unifying nomenclature for the isoforms of the lysosomal membrane protein LAMP-2 SO TRAFFIC LA English DT Editorial Material DE alternative splicing; isoforms; LAMP1; LAMP-1; LAMP2; LAMP-2; lysosome ID GLYCOPROTEINS; CDNA; CARDIOMYOPATHY; BIOSYNTHESIS; ACCUMULATION; TRAFFICKING; MOVEMENT; H-LAMP-1; SEQUENCE; CLONING AB The present nomenclature of the splice variants of the lysosome-associated membrane protein type 2 (LAMP-2) is confusing. The LAMP-2a isoform is uniformly named in human, chicken, and mouse, but the LAMP-2b and LAMP-2c isoforms are switched in human as compared with mouse and chicken. We propose to change the nomenclature of the chicken and mouse b and c isoforms to agree with that currently used for the human isoforms. To avoid confusion in the literature, we further propose to adopt the use of capital letters for the updated nomenclature of all the isoforms in all three species: LAMP-2A, LAMP-2B, and LAMP-2C. C1 Univ Kiel, Inst Biochem, D-2300 Kiel, Germany. Johns Hopkins Med Singapore, Dept Oncol, Div Biomed Sci, Singapore, Singapore. Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA. NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. Univ Autonoma Madrid, Fac Ciencias, Ctr Biol Mol Severo Ochoa, E-28049 Madrid, Spain. Tufts Univ, Sch Med, Boston, MA 02111 USA. Indiana Univ, Sch Med, Dept Microbiol & Immunol, Indianapolis, IN 46202 USA. Natl Ctr Neurol & Psychiat, Natl Inst Neurosci, Dept Neuromuscular Res, Tokyo, Japan. Univ Colorado, Hlth Sci Ctr, Adult Med Genet Program, Aurora, CO 80010 USA. Albert Einstein Coll Med, Bronx, NY 10461 USA. Univ Helsinki, Dept Biol & Environm Sci, Div Biochem, Helsinki, Finland. RP Eskelinen, EL (reprint author), Univ Kiel, Inst Biochem, Olshausenstr 40, D-2300 Kiel, Germany. EM eeva-liisa.eskelinen@helsinki.fi RI Saftig, Paul/A-7966-2010; OI Eskelinen, Eeva-Liisa/0000-0003-0006-7785; Nishino, Ichizo/0000-0001-9452-112X NR 31 TC 51 Z9 59 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1398-9219 J9 TRAFFIC JI Traffic PD NOV PY 2005 VL 6 IS 11 BP 1058 EP 1061 DI 10.1111/j.1600-0854.2005.00337.x PG 4 WC Cell Biology SC Cell Biology GA 968NQ UT WOS:000232169600010 PM 16190986 ER PT J AU Murphy, E Imahashi, K Steenbergen, C AF Murphy, E Imahashi, K Steenbergen, C TI Bcl-2 regulation of mitochondrial energetics SO TRENDS IN CARDIOVASCULAR MEDICINE LA English DT Review ID DEPENDENT ANION CHANNEL; PERMEABILITY TRANSITION PORE; K-ATP CHANNELS; CELL-DEATH; CYTOCHROME-C; TRANSGENIC MICE; OXIDATIVE-PHOSPHORYLATION; DESMIN CYTOSKELETON; ENERGY-METABOLISM; CARDIAC MYOCYTES AB Recent data suggest that in addition to regulating apoptosis, Bcl-2 (an anti-apoptotic protein overexpressed in B-cell lymphoma) and Bcl-2 family members also regulate mitochondrial and cell physiology. t-Bid, a Bcl-2 family member, has been shown to modulate reorganization of mitochondrial cristae. Bcl-2 appears to regulate voltage-dependent anion channel permeability, which has important consequences for mitochondrial transport of adenine nucleotides, Ca2+, and other metabolites. BAD, a pro-apoptotic Bcl-2 family member, is required for the binding of glucokinase to a mitochondrial complex, and BAD null mice have altered glucose homeostasis. It has been suggested that Bcl-2 family members may regulate important mitochondrial/cell functions and serve as sentinels to detect abnormalities in these pathways and, when the abnormalities are severe enough, to initiate or facilitate cell death. Understanding the physiologic processes controlled by Bcl-2 will be important in understanding cell regulation, and it may also provide new insights into the regulation of apoptosis. C1 Natl Inst Environm Hlth Sci, Lab Signal Transduct, Natl Inst Hlth, Res Triangle Pk, NC 27709 USA. Duke Univ, Dept Pathol, Durham, NC 27706 USA. RP Murphy, E (reprint author), Natl Inst Environm Hlth Sci, Lab Signal Transduct, Natl Inst Hlth, 111 Alexander Dr,Maildrop F2-07, Res Triangle Pk, NC 27709 USA. EM murphy1@niehs.nih.gov FU NHLBI NIH HHS [R01 HL039752] NR 73 TC 32 Z9 37 U1 0 U2 1 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1050-1738 J9 TRENDS CARDIOVAS MED JI Trends Cardiovasc. Med. PD NOV PY 2005 VL 15 IS 8 BP 283 EP 290 AR PII S1050-1738(05)00166-0 DI 10.1016/j.tcm.2005.09.002 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 990TC UT WOS:000233765100003 PM 16297765 ER PT J AU Aoyagi, S Archer, TK AF Aoyagi, S Archer, TK TI Modulating molecular chaperone Hsp90 functions through reversible acetylation SO TRENDS IN CELL BIOLOGY LA English DT Article ID HISTONE MODIFICATIONS; DEACETYLASE; HDAC6 AB The molecular chaperone protein Hsp90 is a key regulator of approximately 100 'client' proteins crucial for numerous cell signaling processes. Consequently, understanding the molecular underpinnings that regulate Hsp90 activity is an important biological endeavor. Exciting new results now suggest that, at least for nuclear receptor activity, Hsp90 function is directly regulated by histone deacetylase 6 (HDAC6). These observations have consequences for various biological processes and potentially important implications for the development of cancer therapeutics. 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 12233,111 Alexander Dr, Res Triangle Pk, NC 27709 USA. EM archer1@niehs.nih.gov FU Intramural NIH HHS NR 16 TC 71 Z9 76 U1 0 U2 1 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0962-8924 J9 TRENDS CELL BIOL JI Trends Cell Biol. PD NOV PY 2005 VL 15 IS 11 BP 565 EP 567 DI 10.1016/j.tcb.2005.09.003 PG 3 WC Cell Biology SC Cell Biology GA 990GV UT WOS:000233732100001 PM 16199163 ER PT J AU Wassermann, EM Grafman, J AF Wassermann, EM Grafman, J TI Recharging cognition with DC brain polarization SO TRENDS IN COGNITIVE SCIENCES LA English DT Review ID DIRECT-CURRENT STIMULATION; HUMAN MOTOR CORTEX; EXCITABILITY; HUMANS; FACILITATION; PERCEPTION AB Electrical direct current (DC) has been applied to the human head throughout history for various reasons and with claims of behavioral effects and clinical benefits. This technique has recently been rediscovered and its effects validated with modern quantitative techniques and experimental designs. Despite the very weak current used, DC polarization applied to specific brain areas can after verbal fluency, motor learning and perceptual thresholds, and can be used in conjunction with transcranial magnetic stimulation. Compact and safe, this old technique seems poised to allow major advances cognitive science and therapy. C1 NINDS, Brain Stimulat Unit, NIH, Bethesda, MD 20892 USA. NINDS, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA. RP Wassermann, EM (reprint author), NINDS, Brain Stimulat Unit, NIH, Bethesda, MD 20892 USA. EM wassermanne@ninds.nih.gov OI Grafman, Jordan H./0000-0001-8645-4457 NR 16 TC 88 Z9 90 U1 0 U2 6 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1364-6613 J9 TRENDS COGN SCI JI TRENDS COGN. SCI. PD NOV PY 2005 VL 9 IS 11 BP 503 EP 505 DI 10.1016/i.tics.2005.09.001 PG 3 WC Behavioral Sciences; Neurosciences; Psychology, Experimental SC Behavioral Sciences; Neurosciences & Neurology; Psychology GA 987YC UT WOS:000233552700001 PM 16182596 ER PT J AU Shah, BH Catt, KJ AF Shah, BH Catt, KJ TI Roles of LPA(3) and COX-2 in implantation SO TRENDS IN ENDOCRINOLOGY AND METABOLISM LA English DT Review ID LYSOPHOSPHATIDIC ACID; EMBRYO IMPLANTATION; CANCER; RECEPTORS; OVARIAN; GROWTH; MOUSE; CELLS AB Lysophosphatidic acid (LPA) is a lipid-derived G-protein-coupled receptor (GPCR) agonist that is involved in a variety of physiological and pathological processes, including cell survival, proliferation and differentiation, cytoskeletal rearrangement, cell-cell interactions, tumorigenesis and cell invasion. LPA also stimulates oocyte maturation, the preimplantation development of two- or four-cell embryos to the blastocyst stage and embryo transport in the oviduct. Recent studies revealed that targeted deletion of the LPA3 receptor results in delayed implantation and altered embryo spacing, and significantly reduced litter size in mice. This was attributable to selective downregulation of uterine cyclooxygenase-2 (COX-2), which generates prostaglandins (PGs) E-2 and I-2. Exogenous administration of PGE(2) or the PGI(2) analogue, carba-prostacyclin, to LPA(3)-deficient female mice rescued delayed implantation but did not prevent defects in embryo spacing. These findings indicate that LPA-induced COX-2 induction has a crucial role in implantation and mammalian reproduction. C1 NICHD, Sect Hormonal Regulat Endocrinol & Reprod Res Bra, NIH, Bethesda, MD 20892 USA. RP Shah, BH (reprint author), NICHD, Sect Hormonal Regulat Endocrinol & Reprod Res Bra, NIH, Bethesda, MD 20892 USA. EM shahb@mail.nih.gov NR 16 TC 14 Z9 18 U1 0 U2 2 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1043-2760 J9 TRENDS ENDOCRIN MET JI Trends Endocrinol. Metab. PD NOV PY 2005 VL 16 IS 9 BP 397 EP 399 DI 10.1016/j.tem.2005.09.009 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 987XY UT WOS:000233552300002 PM 16226033 ER PT J AU Alessandro, R Fontana, S Kohn, E De Leo, G AF Alessandro, R Fontana, S Kohn, E De Leo, G TI Proteomic strategies and their application in cancer research SO TUMORI LA English DT Review DE cancer proteomics; protein microarray; proteomics technologies; tumor markers ID MASS-SPECTROMETRY; BREAST-CANCER; OVARIAN-CANCER; PROTEIN MICROARRAYS; CLINICAL-APPLICATIONS; BIOMARKER DISCOVERY; GEL-ELECTROPHORESIS; COLON-CANCER; CELL LINES; IDENTIFICATION AB The understanding of carcinogenesis and tumor progression on a molecular basis needs a detailed study of proteins as effector molecules and as critical components of the multiple interconnected signaling pathways that drive the neoplastic phenotype. Thus, the proteomic approach represents a powerful tool for the challenge of the post-genomic era. The term "cancer proteome" refers to the collection of proteins expressed by a given cancer cell and should be considered as a highly dynamic entity within the cell, which affects a variety of cellular activities. The emerging proteomic analysis platforms including 2D-PAGE, mass spectrometry technologies, and protein microarrays represent powerful tools to study and understand cancer. These systems aim to not only identify, catalogue, and characterize cancer proteins, but also to unveil how they interact to affect overall tumor progression. Moreover, recent studies on various cancers have reported promising results concerning the detection of novel molecular biomarkers useful in the early diagnosis of cancer and in drug discovery. Thus, a new subdiscipline named clinical proteomics, concomitant with new molecular technologies that are developed, demonstrates promise to discover new cancer biomarkers. The early diagnosis of cancer, even in a premalignant state, is crucial for the successful treatment of this disease. For these reasons, it is clear that the identification of biomarkers for the early diagnosis of cancer should represent one of the main goals of this emergng field of study. C1 Univ Palermo, Dipartimento Biopatol & Metodol Biomed, I-90133 Palermo, Italy. NCI, Mol Signaling Sect, Pathol Lab, Canc Res Ctr, Bethesda, MD 20892 USA. RP Alessandro, R (reprint author), Univ Palermo, Dipartimento Biopatol & Metodol Biomed, Via Divisi 83, I-90133 Palermo, Italy. EM ricale@unipa.it OI Fontana, Simona/0000-0003-4681-2170 NR 60 TC 18 Z9 20 U1 0 U2 0 PU PENSIERO SCIENTIFICO EDITOR PI ROME PA VIA BRADANO 3/C, 00199 ROME, ITALY SN 0300-8916 J9 TUMORI JI Tumori PD NOV-DEC PY 2005 VL 91 IS 6 BP 447 EP 455 PG 9 WC Oncology SC Oncology GA 041GP UT WOS:000237442700001 PM 16457140 ER PT J AU Katz, LM Doyle, JJ Bergemann, R Siegartel, LR Stern, LS Chalfin, D Danis, M Rapoport, J Levy, M AF Katz, LM Doyle, JJ Bergemann, R Siegartel, LR Stern, LS Chalfin, D Danis, M Rapoport, J Levy, M TI Use of a modified recursive partitioning and amalgamation (RECPAM) technique in outcomes research SO VALUE IN HEALTH LA English DT Meeting Abstract C1 Analyt Int, New York, NY USA. Analyt Int, Lorrach, Germany. Montefiore Med Ctr, Port Washington, NY USA. NIH, Bethesda, MD 20892 USA. Mt Holyoke Coll, S Hadley, MA 01075 USA. Brown Univ, Providence, RI 02912 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1098-3015 J9 VALUE HEALTH JI Value Health PD NOV-DEC PY 2005 VL 8 IS 6 BP A1 EP A1 DI 10.1111/j.1524-4733.2005.00062.x PG 1 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 980MD UT WOS:000233021700008 ER PT J AU Shia, J Qin, J Erlandson, RA King, R Illei, P Nobrega, J Yao, D Klimstra, DS AF Shia, J Qin, J Erlandson, RA King, R Illei, P Nobrega, J Yao, D Klimstra, DS TI Malignant mesothelioma with a pronounced myxoid stroma: a clinical and pathological evaluation of 19 cases SO VIRCHOWS ARCHIV LA English DT Article; Proceedings Paper CT 93rd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 06-12, 2004 CL Vancouver, CANADA SP US & Canadian Acad Pathol DE myxoid mesothelioma; epithelioid mesothelioma; survival; immunohistochemistry; electron microscopy ID POSITIVE EPITHELIAL MESOTHELIOMA; PLEURAL MESOTHELIOMA; PROGNOSTIC-FACTORS; EXPERIENCE AB Mesothelioma with a pronounced myxoid stroma has been identified as a morphological pattern that might portend a better prognosis. Reports on this type of cases are few. Its clinical and pathological features are not defined. In this study, we identified 19 such cases from a series of 234 pleural mesotheliomas and performed a comprehensive clinical and pathological analysis. The inclusion criteria were mesotheliomas with at least 50% of the tumor exhibiting a pronounced myxoid stroma that occupied more than 50% of the tumor volume (designated as myxoid mesothelioma). There were ten males and nine females, with a median age of 58 years. Forty seven percent of the patients had probable or definite asbestos exposure. Patients presented at various stages [International Mesothelioma Interest Group (IMIG) stage II, 4; stage III, 9; and stage IV, 6]. Most (16/19) patients were treated by extrapleural pneumonectomy with adjuvant radiation or chemotherapy or both. Overall, the median survival rate was 36 months (median follow-up time, 17 months), and the 2-year survival rate was 79%. Histologically, the tumor cell component was entirely epithelioid without significant cytologic atypia. The myxoid material stained positive for Alcian blue, and the staining diminished after treatment with hyaluronidase in 12 of 12 cases. The tumor cells showed a typical mesothelial immunophenotype. Ultrastructurally, all six tumors examined had typical mesothelial-type surface microvilli and a moderately electron-dense extracellular amorphous material that often formed a haze enmeshing the surface microvilli. Hyaluronic acid-type, fern-like crystals were noted in all cases. These findings show that myxoid mesotheliomas represent a group of epithelioid mesotheliomas that have retained the secretory activity of normal mesothelium. Patients may present at different stages, but survival appears to be superior to that of epithelioid mesotheliomas in general. Our study emphasizes the need for better attention to histologic subtypes, particularly in the context of prognostically or therapeutically oriented investigations of this lethal disease. C1 Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA. Knoxville Dermatol Lab, Knoxville, TN USA. NYU, Med Ctr, Dept Pathol, New York, NY 10016 USA. RP Klimstra, DS (reprint author), Mem Sloan Kettering Canc Ctr, Dept Pathol, 1275 York Ave, New York, NY 10021 USA. EM klimstrd@mskcc.org OI Shia, Jinru/0000-0002-4351-2511 NR 22 TC 8 Z9 10 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0945-6317 J9 VIRCHOWS ARCH JI Virchows Arch. PD NOV PY 2005 VL 447 IS 5 BP 828 EP 834 DI 10.1007/s00428-005-0035-y PG 7 WC Pathology SC Pathology GA 988ZM UT WOS:000233642700008 PM 16021506 ER PT J AU Song, X Tao, YG Zeng, L Deng, XY Lee, LM Gong, JP Wu, Q Cao, Y AF Song, X Tao, YG Zeng, L Deng, XY Lee, LM Gong, JP Wu, Q Cao, Y TI Latent membrane protein 1 encoded by Epstein-Barr virus modulates directly and synchronously cyclin D1 and p16 by newly forming a c-Jun/Jun B heterodimer in nasopharyngeal carcinoma cell line SO VIRUS RESEARCH LA English DT Article DE latent membrane protein 1; nasopharyngeal carcinoma; Epstein-Barr virus; activator protein 1; heterodimer; c-Jun; Jun B; p16; cyclin D1; cell cycle ID NF-KAPPA-B; MEMBRANE-PROTEIN 1; BREAST-CANCER CELLS; TRANSCRIPTION FACTOR; JUN-B; GENE-PRODUCT; DNA-BINDING; IN-VIVO; EXPRESSION; DIFFERENTIATION AB Recently we confirmed that latent membrane protein 1 (LMP1) encoded by Epstein-Barr virus (EBV) accelerates a newly forming active c-Jun/Jun B heterodimer, a transcription factor, but little is known about the target gene regulated by it. In this paper, results indicated that a c-Jun/Jun B heterodimer induced by LMP1 upregulated cyclin D1 promoters activity and expression, on the contrary, downregulated p16, and maladjustment of cyclin D1 and p16 expression accelerated progression of cell cycle. Firstly, we found a c-Jun/Jun B heterodimer regulated synchronously and directly cyclin D1 and p16 in the Tet-on-LMP1-HNE2 cell line, in which LMP1 expression is regulated by Tet-on system. This paper investigated in depth function of the newly forming active c-Jun/Jun B heterodimer, and built new connection between environmental pathogenic factor, signal transduction and cell cycle. (c) 2005 Elsevier B.V. All rights reserved. C1 Cent S Univ, Canc Res Inst, Xiangya Sch Med, Changsha 410078, Peoples R China. Wayne State Univ, Dept Pathol, Sch Med, Detroit, MI 48201 USA. NCI, SAIC Frederick, Lab Mol Technol, Frederick, MD 21702 USA. Tongji Med Univ, Tongji Hosp, Mol Med Ctr, Wuhan 430030, Peoples R China. Xiamen Univ, Sch Life Sci, Key Lab, Minist Educ Cell Biol & Tumor Cell Engn, Xiamen 361005, Peoples R China. RP Cao, Y (reprint author), Cent S Univ, Canc Res Inst, Xiangya Sch Med, 88 Rd Xiangya, Changsha 410078, Peoples R China. EM ycao98@public.cs.hn.cn RI Wu, Q/G-4646-2010 NR 79 TC 12 Z9 14 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1702 EI 1872-7492 J9 VIRUS RES JI Virus Res. PD NOV PY 2005 VL 113 IS 2 BP 89 EP 99 DI 10.1016/j.virusres.2005.04.019 PG 11 WC Virology SC Virology GA 973CK UT WOS:000232500300003 PM 15936839 ER PT J AU Sheliga, BM Chen, KJ FltzGibbon, EJ Miles, FA AF Sheliga, BM Chen, KJ FltzGibbon, EJ Miles, FA TI Initial ocular following in humans: A response to first-order motion energy SO VISION RESEARCH LA English DT Article DE visual motion; energy-based mechanisms; missing fundamental; spatio-temporal filtering ID PURSUIT EYE-MOVEMENTS; HUMAN VISUAL-SYSTEM; 2ND-ORDER MOTION; OPTOKINETIC NYSTAGMUS; BINOCULAR DISPARITY; STEREOSCOPIC CONTOURS; 3-SYSTEMS THEORY; APPARENT MOTION; BRAIN-DAMAGE; HUMAN VISION AB Visual motion is sensed by low-level (energy-based) and high-level (feature-based) mechanisms. Ocular following responses (OFR) were elicited in humans by applying horizontal motion to vertical square-wave gratings lacking the fundamental ("missing fundamental stimulus"). Motion consisted of successive 1/4-wavelength steps, so the features and 4n + I harmonics (where n = integer) shifted forwards, whereas the 4n - I harmonics-including the strongest Fourier component (the 3rd harmonic)-shifted backwards (spatial aliasing). Initial OFR, recorded with the electromagnetic search coil technique, were always in the direction of the 3rd harmonic, e.g., leftward steps resulted in rightward OFR. Thus, the earliest OFR were strongly dependent on the motion of the major Fourier component, consistent with early spatio-temporal filtering prior to motion detection, as in the well-known energy model of motion analysis. Published by Elsevier Ltd. C1 NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. RP Sheliga, BM (reprint author), NEI, Sensorimotor Res Lab, NIH, Bldg 49 Room 2A50,49 Convent Dr, Bethesda, MD 20892 USA. EM bms@lsr.nei.nih.gov FU NEI NIH HHS [Z01 EY000153-22] NR 65 TC 54 Z9 55 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0042-6989 J9 VISION RES JI Vision Res. PD NOV PY 2005 VL 45 IS 25-26 BP 3307 EP 3321 DI 10.1016/j.visres.2005.03.011 PG 15 WC Neurosciences; Ophthalmology SC Neurosciences & Neurology; Ophthalmology GA 985BB UT WOS:000233350000021 PM 15894346 ER PT J AU Macfoy, C Danosus, D Sandit, R Jones, TH Garraffo, HM Spande, TE Daly, JW AF Macfoy, C Danosus, D Sandit, R Jones, TH Garraffo, HM Spande, TE Daly, JW TI Alkaloids of anuran skin: Antimicrobial function? SO ZEITSCHRIFT FUR NATURFORSCHUNG C-A JOURNAL OF BIOSCIENCES LA English DT Article DE alkaloids; antibiotics; antifungals ID POISON FROGS DENDROBATIDAE; AMPHIBIAN SKIN; IMIDAZOLE-ALKYLAMINES; PHENYL-ALKYLAMINES; INDOLE-ALKYLAMINES; AUSTRALIAN FROG; PUMILIOTOXINS; PEPTIDES; PSEUDOPHRYNE; TOADS AB A variety of alkaloids, most of which occur or are structurally related to alkaloids that occur in skin glands of dendrobatid poison frogs, were assayed for antimicrobial activity against the Gram-positive bacterium Bacillus subtilis, the Gram-negative bacterium Escherichia coli and the fungus Candida albicans. Certain pyrrolidines, piperidines and decahydroquinolines, perhydro-histrionicotoxin, and a synthetic pumiliotoxin were active against B. subtilis. Only 2-n-nonylpiperidine was active against E. coli. One pyrrolidine, two piperidines, two decahydroquinolines, and the synthetic pumiliotoxin were active against the fungus C. albicans. The results suggest that certain of the skin alkaloids of poison frogs, in addition to being noxious to predators, may also benefit the frog through protection against skin infections. C1 NIDDKD, Bioorgan Chem Lab, NIH, DHHS, Bethesda, MD 20892 USA. American Univ, Dept Biol, Washington, DC 20016 USA. Virginia Mil Inst, Chem Lab, Lexington, VA 24450 USA. RP Daly, JW (reprint author), NIDDKD, Bioorgan Chem Lab, NIH, DHHS, Bethesda, MD 20892 USA. EM jdaly@nih.gov NR 25 TC 15 Z9 16 U1 0 U2 12 PU VERLAG Z NATURFORSCH PI TUBINGEN PA POSTFACH 2645, W-7400 TUBINGEN, GERMANY SN 0939-5075 J9 Z NATURFORSCH C JI Z.Naturforsch.(C) PD NOV-DEC PY 2005 VL 60 IS 11-12 BP 932 EP 937 PG 6 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 006WA UT WOS:000234927200018 PM 16402556 ER PT J AU Low, AF O'Donnell, CJ Kathiresan, S Everett, B Chae, CU Shaw, SY Ellinor, PT MacRae, CA AF Low, AF O'Donnell, CJ Kathiresan, S Everett, B Chae, CU Shaw, SY Ellinor, PT MacRae, CA TI Aging syndrome genes and premature coronary artery disease SO BMC MEDICAL GENETICS LA English DT Article ID HUTCHINSON-GILFORD PROGERIA; LAMIN-A; HEART-DISEASE; RISK-FACTORS; ASSOCIATION; KLOTHO; SUSCEPTIBILITY; MUTATIONS; DESIGNS; LOCUS AB Background: Vascular disease is a feature of aging, and coronary vascular events are a major source of morbidity and mortality in rare premature aging syndromes. One such syndrome is caused by mutations in the lamin A/C (LMNA) gene, which also has been implicated in familial insulin resistance. A second gene related to premature aging in man and in murine models is the KLOTHO gene, a hypomorphic variant of which (KL-VS) is significantly more common in the first-degree relatives of patients with premature coronary artery disease (CAD). We evaluated whether common variants at the LMNA or KLOTHO genes are associated with rigorously defined premature CAD. Methods: We identified 295 patients presenting with premature acute coronary syndromes confirmed by angiography. A control group of 145 patients with no evidence of CAD was recruited from outpatient referral clinics. Comprehensive haplotyping of the entire LMNA gene, including the promoter and untranslated regions, was performed using a combination of TaqMan(R) probes and direct sequencing of 14 haplotype-tagging single nucleotide polymorphisms (SNPs). The KL-VS variant of the KLOTHO gene was typed using restriction digest of a PCR amplicon. Results: Two SNPs that were not in Hardy Weinberg equilibrium were excluded from analysis. We observed no significant differences in allele, genotype or haplotype frequencies at the LMNA or KLOTHO loci between the two groups. In addition, there was no evidence of excess homozygosity at the LMNA locus. Conclusion: Our data do not support the hypothesis that premature CAD is associated with common variants in the progeroid syndrome genes LMNA and KLOTHO. C1 Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NHLBI, NIH, Bethesda, MD 20892 USA. Framingham Heart Dis Epidemiol Study, Framingham, MA USA. RP MacRae, CA (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. EM mdclowa@nus.edu.sg; codonnell@partners.org; skathiresan@partners.org; beverett@partners.org; cchae@partners.org; sshaw@partners.org; pellinor@partners.org; cmacrae@partners.org FU NHLBI NIH HHS [HL-71632, K23 HL071632]; NIA NIH HHS [R21 AG037925] NR 28 TC 19 Z9 20 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2350 J9 BMC MED GENET JI BMC Med. Genet. PD OCT 31 PY 2005 VL 6 AR 38 DI 10.1186/1471-2350-6-38 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 987XK UT WOS:000233550800001 PM 16262891 ER PT J AU Chae, S Yun, C Um, H Lee, JH Cho, H AF Chae, S Yun, C Um, H Lee, JH Cho, H TI Centrosome amplification and multinuclear phenotypes are Induced by hydrogen peroxide SO EXPERIMENTAL AND MOLECULAR MEDICINE LA English DT Article DE antioxidants; centrosome, giant cells, hydrogen peroxide, reactive oxygen species ID CHROMOSOME INSTABILITY; SIGNAL-TRANSDUCTION; CANCER; CELLS; TELOMERES; OVEREXPRESSION; ONCOPROTEIN; HEPATITIS; STRESS; MICE AB Multinucleated cells resulted from mitosis defect have been noted in pathophysiological states of the cells such as inflammation, senescence and cancer. Since oxidative stress has been known to correlate with these pathophysiological conditions, we tested the effect of H2O2 on the cell cycle progression and formation of multinucleated cells. H2O2 induced a significant delay in cell cycle progression in Chang liver cells. Interestingly, H2O2 actively induced hyper-amplification of centrosomes (n >= 3) and multipolar spindle formation during mitosis and subsequently increased the generation of multinucleated cells. A significant increase of the phospho-ERK level was observed upon H2O2 treatment but PD98059, an MEK1/2 inhibitor, didn't reduce the frequency of cells with hyperamplified centrosomes. On the other hand, treatment of either H2O2 or adriamycin increased intracellular ROS levels and multinucleated cells, which were significantly suppressed by antioxidants, N-acetylcysteine and PDTC. Thus, our results suggest that oxidative stress can trigger centrosome hyperamplification and multinucleated cell formation, which may promote pathophysiological progression. C1 Ajou Univ, Sch Med, Dept Biochem & Mol Biol, Chron Inflammatory Dis Res Ctr, Suwon 442749, South Korea. NICHD, Lab Gene Regulat & Dev, Bethesda, MD USA. RP Cho, H (reprint author), Ajou Univ, Sch Med, Dept Biochem & Mol Biol, Chron Inflammatory Dis Res Ctr, Suwon 442749, South Korea. EM hscho@ajou.ac.kr NR 25 TC 23 Z9 23 U1 0 U2 0 PU KOREAN SOC MED BIOCHEMISTRY MOLECULAR BIOLOGY PI SEOUL PA #812 KOFST, 635-4 YOKSAM-DONG KANGNAM-GU, SEOUL 135-703, SOUTH KOREA SN 1226-3613 J9 EXP MOL MED JI Exp. Mol. Med. PD OCT 31 PY 2005 VL 37 IS 5 BP 482 EP 487 PG 6 WC Biochemistry & Molecular Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Research & Experimental Medicine GA 980PE UT WOS:000233029700012 ER PT J AU Lim, HW Hong, S Jin, W Lim, S Kim, SJ Kang, HJ Park, EH Ahn, K Lim, CJ AF Lim, HW Hong, S Jin, W Lim, S Kim, SJ Kang, HJ Park, EH Ahn, K Lim, CJ TI Up-regulation of defense enzymes is responsible for low reactive oxygen species in malignant prostate cancer cells SO EXPERIMENTAL AND MOLECULAR MEDICINE LA English DT Article DE catalase; glutathione; glutathione reductase; glutathione S-transferase; metastasis; oxidative stress; prostatic neoplasms; thioredoxin ID GLUTATHIONE-S-TRANSFERASE; OXIDATIVE STRESS; HYDROGEN-PEROXIDE; DIFFERENTIAL EXPRESSION; GENE-EXPRESSION; DU145 CELLS; LINES; ANTIOXIDANT; MASPIN; METASTASIS AB Reactive oxygen species (ROS) are involved in a diversity of important phenomena in the process of tumor development. To investigate the alterations of oxidative stress and their related systems in tumor progression, a variety of components in the antioxidative stress defense system were examined in prostate cancer cell lines, PC3 and LNCaP. Cell surface molecules involved in metastasis were expressed highly in PC3 cells compared with LNCaP cells, and strong invasion ability was shown in PC3 cells only. ROS level in LNCaP cells was twice higher than that in PC3 cells, although nitric oxide (NO) level was similar between the two cell lines. The content of GSH increased up to about 2-fold in PC3 compared with LNCaP. Activities of glutathione reductase, thioredoxin reductase, and glutathione S-transferase except catalase are significantly higher in PC3 cells than in LNCaP cells. Furthermore,, oxidative stress-inducing agents caused down-regulation of GSH and glutathione S-transferase much more significantly in LNCaP cells than in PC3 cells. These results imply that malignant tumor cells may maintain low ROS content by preserving relatively high anti-oxidative capacity, even in the presence of stressful agents. C1 Kangweon Natl Univ, Div Life Sci, Chunchon 200701, South Korea. NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. Sookmyung Womens Univ, Coll Pharm, Seoul 140742, South Korea. Baekseok Coll, Dept Hlth & Environm, Cheonan 330705, South Korea. RP Lim, CJ (reprint author), Kangweon Natl Univ, Div Life Sci, Chunchon 200701, South Korea. EM cjlim@kangwon.ac.kr NR 55 TC 24 Z9 26 U1 0 U2 1 PU KOREAN SOC MED BIOCHEMISTRY MOLECULAR BIOLOGY PI SEOUL PA #812 KOFST, 635-4 YOKSAM-DONG KANGNAM-GU, SEOUL 135-703, SOUTH KOREA SN 1226-3613 J9 EXP MOL MED JI Exp. Mol. Med. PD OCT 31 PY 2005 VL 37 IS 5 BP 497 EP 506 PG 10 WC Biochemistry & Molecular Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Research & Experimental Medicine GA 980PE UT WOS:000233029700015 PM 16264276 ER PT J AU Chung, HJ Levens, D AF Chung, HJ Levens, D TI c-myc Expression: Keep the noise down! SO MOLECULES AND CELLS LA English DT Review DE c-myc promoter; extrinsic noise; FBP; intrinsic noise; MYC; TFIIH ID RNA-POLYMERASE-II; SINGLE-STRANDED-DNA; GENE-EXPRESSION; MESSENGER-RNA; BINDING-PROTEIN; TRANSCRIPTION FACTOR; XERODERMA-PIGMENTOSUM; CELL COMPETITION; PROMOTER ESCAPE; SMALL-MOLECULE AB The c-myc proto-oncogene encodes a nuclear protein that is deregulated and/or mutated in most human cancers. Acting primarily as an activator and sometimes as a repressor, MYC protein controls the synthesis of up to 10-15% of genes. The key MYC targets contributing to oncogenesis are incompletely enumerated and it is not known whether pathology arises from the expression of physiologic targets at abnormal levels or from the pathologic response of new target genes that are not normally regulated by MYC. Regardless of which, available evidence indicates that the level of MYC expression is an important determinant of MYC biology. The c-myc promoter has architectural and functional features that contribute to uniform expression and help to prevent or mitigate conditions that might otherwise create noisy expression. Those features include the use of an expanded proximal promoter, the averaging of input from dozens of transcription factors, and real-time feedback using the supercoil-deformable Far UpStream Element (FUSE) as physical sensor of ongoing transcriptional activity, and the FUSE binding protein (FBP) as well as the FBP interacting repressor (FIR) as effectors to enforce normal transcription from the c-myc promoter. C1 NCI, Pathol Lab, Bethesda, MD 20892 USA. RP Chung, HJ (reprint author), NCI, Pathol Lab, Bethesda, MD 20892 USA. EM levens@helix.nih.gov RI Levens, David/C-9216-2009 OI Levens, David/0000-0002-7616-922X NR 80 TC 58 Z9 62 U1 1 U2 8 PU SPRINGER SINGAPORE PTE LTD PI SINGAPORE PA #04-01 CENCON I, 1 TANNERY RD, SINGAPORE 347719, SINGAPORE SN 1016-8478 J9 MOL CELLS JI Mol. Cells PD OCT 31 PY 2005 VL 20 IS 2 BP 157 EP 166 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 980GC UT WOS:000233001400001 PM 16267388 ER PT J AU Pozsgay, V Kubler-Kielb, J Coxon, B Ekborg, G AF Pozsgay, V Kubler-Kielb, J Coxon, B Ekborg, G TI Synthesis of two glycolipid antigens of the causative agent of Lyme disease SO TETRAHEDRON LA English DT Article DE Borrelia burkholderi; cholesterol; glycolipid; Lyme disease; vaccine ID BORRELIA-BURGDORFERI; CHOLESTERYL GLUCOSIDE; ALLYL ETHERS; ISOMERIZATION; ARTHRITIS; ACIDS AB As a prelude to development of a human vaccine against Lyme disease, the first chemical synthesis of glycolipid antigens of Borrelia burkholderi is reported. First, cholesteryl D-D-galactopyranoside was synthesized and was converted to partially protected congeners having the HO-6 group of the galactose moiety unprotected. Treatment of these intermediates with palmitic and oleic acid, respectively, under dehydrative conditions followed by removal of the protecting groups afforded cholesteryl 6-O-palmitoyl/oleoyl-beta-D-galactopyranosides that were identical to the glycolipids isolated from B. burkholderi. Published by Elsevier Ltd. C1 NICHHD, NIH, Bethesda, MD 20892 USA. RP Pozsgay, V (reprint author), NICHHD, NIH, 31 Ctr Dr MSC 2423, Bethesda, MD 20892 USA. EM pozsgayv@mail.nih.gov NR 27 TC 7 Z9 7 U1 0 U2 5 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 OCT 31 PY 2005 VL 61 IS 44 BP 10470 EP 10481 DI 10.1016/j.tet.2005.08.053 PG 12 WC Chemistry, Organic SC Chemistry GA 974DR UT WOS:000232572000006 ER PT J AU Hama, Y Yakushiji, T Iwasaki, Y Kaji, T Isomura, N Kusano, S AF Hama, Y Yakushiji, T Iwasaki, Y Kaji, T Isomura, N Kusano, S TI Small left atrium: An adjunctive sign of hemodynamically compromised massive pulmonary embolism SO YONSEI MEDICAL JOURNAL LA English DT Article DE diagnostic imaging; cardiac output; computed tomography; echocardiography; thrombolytic therapy ID HELICAL CT; SPIRAL CT AB Pulmonary embolism (PE) is a common disease with a high mortality rate due to right ventricular dysfunction and underfilling of the left ventricle. We present a case of a 33-year-old man with hemodynamically compromised massive PE. His left atrium was collapsed with marked dilatation of the fight atrium and ventricle on multi-detector-row CT scans. The patient was treated with an intracatheter injection of a mutant tissue-type plasminogen activator and subsequently showed clinical and radiological improvements. The small left atrial size in combination with a fight ventricular pressure overload was considered to be an adjunctive sign of hemodynamically compromised massive PE. C1 NCI, Radiat Biol Branch, NIH, Bethesda, MD 20892 USA. Natl Def Med Coll, Dept Radiol, Tokorozawa, Saitama 359, Japan. Natl Def Med Coll, Dept Internal Med, Tokorozawa, Saitama 359, Japan. RP Hama, Y (reprint author), NCI, Radiat Biol Branch, NIH, Bldg 10,Room B3B69, Bethesda, MD 20892 USA. EM yjhama2005@yahoo.co.jp FU Intramural NIH HHS NR 13 TC 4 Z9 4 U1 0 U2 1 PU YONSEI UNIV COLLEGE MEDICINE PI SEOUL PA C/O KYUN0-IL IM, M.D., PH.D, SHINCHON DONG 134, SEODAEMOON KU, SEOUL 120-752, SOUTH KOREA SN 0513-5796 J9 YONSEI MED J JI Yonsei Med. J. PD OCT 31 PY 2005 VL 46 IS 5 BP 733 EP 736 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 985XR UT WOS:000233412500023 PM 16259077 ER PT J AU Katki, HA Engels, EA Rosenberg, PS AF Katki, HA Engels, EA Rosenberg, PS TI Assessing uncertainty in reference intervals via tolerance intervals: application to a mixed model describing HIV infection SO STATISTICS IN MEDICINE LA English DT Article DE reference interval; tolerance interval; Bayesian statistics; linear mixed models; growth curves ID HUMAN-IMMUNODEFICIENCY-VIRUS; RNA LEVELS; HEMOPHILIA; TYPE-1; AIDS AB We define the reference interval as the range between the 2.5th and 97.5th percentiles of a random variable. We use reference intervals to compare characteristics of a marker of disease progression between affected populations. We use a tolerance interval to assess uncertainty in the reference interval. Unlike the tolerance interval, the estimated reference interval does not contains the true reference interval with specified confidence (or credibility). The tolerance interval is easy to understand, communicate and visualize. We derive estimates of the reference interval and its tolerance interval for markers defined by features of a linear mixed model. Examples considered are reference intervals for time trends in HIV viral load, and CD4 per cent, in HIV-infected haemophiliac children and homosexual men. We estimate the intervals with likelihood methods and also develop a Bayesian model in which the parameters are estimated via Markov-chain Monte Carlo. The Bayesian formulation naturally overcomes some important limitations of the likelihood model. Published in 2005 by John Wiley & Sons, Ltd. C1 NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA. RP NCI, Div Canc Epidemiol & Genet, NIH, DHHS 6120 Execut Blvd, Rockville, MD 20852 USA. EM katkih@mail.nih.gov RI Katki, Hormuzd/B-4003-2015 NR 26 TC 7 Z9 8 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0277-6715 EI 1097-0258 J9 STAT MED JI Stat. Med. PD OCT 30 PY 2005 VL 24 IS 20 BP 3185 EP 3198 DI 10.1002/sim.2171 PG 14 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 975OL UT WOS:000232671700009 PM 16189804 ER PT J AU Minn, AH Pise-Masison, CA Radonovich, M Brady, JN Wang, P Kendziorski, C Shalev, A AF Minn, AH Pise-Masison, CA Radonovich, M Brady, JN Wang, P Kendziorski, C Shalev, A TI Gene expression profiling in INS-1 cells overexpressing thioredoxin-interacting protein SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE thioredoxin; pancreatic beta-cells; diabetes; apoptosis; insulin secretion; RAB27A; microarray; transcriptional repressor ID UP-REGULATED PROTEIN-1; COMBINED HYPERLIPIDEMIA; INDUCED APOPTOSIS; SOMATOSTATIN RECEPTOR; OXIDATIVE STRESS; GLUCOSE; GROWTH; PAR-4; PATHWAY; RAB27A AB Thioredoxin-interacting protein (TXNIP) is overexpressed in diabetes and has deleterious effects on pancreatic beta-cells and the cardiovascular system. TXNIP is a regulator of the cellular redox state, but has also been suggested to act as a transcriptional repressor. However, the genes and pathways regulated by TXNIP remain unknown. We therefore compared gene expression in INS-1 insulinoma P-cells overexpressing TXNIP and control LacZ-overexpressing cells using the Affymetrix 230A rat chip. Analysis with the Bayes methodology revealed 98 differentially expressed genes, 90 of which were down-regulated, consistent with the predicted role of TXNIP as a repressor. Using the PathwayAssist software, we found that affected genes were involved in cell death/survival and insulin secretion, and confirmed these findings by real-time RT-PCR and by functional studies. Thus, aside from regulating the cellular redox, TXNIP does modulate overall gene transcription and thereby may further enhance beta-cell death and impair insulin secretion. (c) 2005 Elsevier Inc. All rights reserved. C1 Univ Wisconsin, Dept Med, Madison, WI 53706 USA. NCI, NIH, Bethesda, MD 20892 USA. RP Shalev, A (reprint author), Univ Wisconsin, Dept Med, Madison, WI 53706 USA. EM as7@medicine.wisc.edu NR 39 TC 35 Z9 37 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 OCT 28 PY 2005 VL 336 IS 3 BP 770 EP 778 DI 10.1016/j.bbrc.2005.08.161 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 969SM UT WOS:000232255000007 PM 16143294 ER PT J AU Imahashi, K Pott, C Goldhaber, JI Steenbergen, C Philipson, KD Murphy, E AF Imahashi, K Pott, C Goldhaber, JI Steenbergen, C Philipson, KD Murphy, E TI Cardiac-specific ablation of the Na+-Ca2+ exchanger confers protection against ischemia/reperfusion injury SO CIRCULATION RESEARCH LA English DT Article DE Na+-Ca2+ exchange; genetically altered mice; ischemia/reperfusion injury ID SODIUM-CALCIUM EXCHANGE; CYTOSOLIC-FREE CALCIUM; PERFUSED RAT-HEART; NA+-H+ EXCHANGE; INTRACELLULAR NA+; METABOLIC INHIBITION; NA+/CA2+ EXCHANGER; ISCHEMIC-INJURY; REPERFUSION; CONTRACTION AB During ischemia and reperfusion, with an increase in intracellular Na+ and a depolarized membrane potential, Ca2+ may enter the myocyte in exchange for intracellular Na+ via reverse-mode Na+-Ca2+ exchange (NCX). To test the role of Ca2+ entry via NCX during ischemia and reperfusion, we studied mice with cardiac-specific ablation of NCX (NCX-KO) and demonstrated that reverse-mode Ca2+ influx is absent in the NCX-KO myocytes. Langendorff perfused hearts were subjected to 20 minutes of global ischemia followed by 2 hours of reperfusion, during which time we monitored high-energy phosphates using P-31-NMR and left-ventricular developed pressure. In another group of hearts, we monitored intracellular Na+ using Na-23-NMR. Consistent with Ca2+ entry via NCX during ischemia, we found that hearts lacking NCX exhibited less of a decline in ATP during ischemia, delayed ischemic contracture, and reduced maximum contracture. Furthermore, on reperfusion following ischemia, NCX-KO hearts had much less necrosis, better recovery of left-ventricular developed pressure, improved phosphocreatine recovery, and reduced Na+ overload. The improved recovery of function following ischemia in NCX-KO hearts was not attributable to the reduced preischemic contractility in NCX- KO hearts, because when the preischemic workload was matched by treatment with isoproterenol, NCX-KO hearts still exhibited improved postischemic function compared with wild-type hearts. Thus, NCX- KO hearts were significantly protected against ischemia-reperfusion injury, suggesting that Ca2+ entry via reverse-mode NCX is a major cause of ischemia/reperfusion injury. C1 NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. Univ Calif Los Angeles, Dept Physiol, Cardiovasc Res Labs, David Geffen Sch Med, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Med, Cardiovasc Res Labs, David Geffen Sch Med, Los Angeles, CA USA. Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27706 USA. RP Murphy, E (reprint author), NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. EM murphy1@niehs.nih.gov FU NHLBI NIH HHS [HL-39752, HL-48509, R01 HL039752] NR 31 TC 88 Z9 91 U1 1 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD OCT 28 PY 2005 VL 97 IS 9 BP 916 EP 921 DI 10.1161/01.RES.0000187456.06162.cb PG 6 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 978OX UT WOS:000232884000010 PM 16179590 ER PT J AU Santoso, S Orlova, VV Song, KM Sachs, UJ Andrei-Selmer, CL Chavakis, T AF Santoso, S Orlova, VV Song, KM Sachs, UJ Andrei-Selmer, CL Chavakis, T TI The homophilic binding of junctional adhesion molecule-C mediates tumor cell-endothelial cell interactions SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID JAM FAMILY-MEMBERS; IMMUNOGLOBULIN SUPERFAMILY; TRANSENDOTHELIAL MIGRATION; HUMAN PLATELETS; LIGAND; COUNTERRECEPTOR; EXPRESSION; INTEGRINS; RECEPTOR AB The junctional adhesion molecule C(JAM-C) was recently shown to undergo a heterophilic interaction with the leukocyte beta 2 integrin Mac-1, thereby mediating interactions between vascular cells in inflammatory cell recruitment. Here, the homophilic interaction of JAM-C is presented and functionally characterized to mediate tumor cell-endothelial cell interactions. Recombinant soluble JAM-C in fluid phase bound to immobilized JAM-C as assessed in a purified system; moreover, JAM-C-transfected Chinese hamster ovary (CHO) cells adhered to immobilized JAM-C. The homophilic interaction of JAM-C was mediated by the isolated amino-terminal Ig domain (D1), but not the carboxyl-terminal Ig domain (D2), of the molecule. Dimerization of JAM-A is dependent on the sequence RVE in the amino-terminal Ig domain. This motif is conserved in JAM-C (Arg(64)-Ile(65)-Glu(66)), and a single amino acid mutation in this motif (E66R) abolished the homophilic interaction of JAM-C. The lung carcinoma cell line NCI-H522 was found to express JAM-C. NCI-H522 cells adhered to immobilized JAM-C, as well as to JAM-C-transfected CHO cells, but not to mock-transfected CHO cells or to CHO cells transfected with the JAM-Cmutant ( E66R). Adhesion of NCI-H522 cells to JAM-C protein or JAM-C-transfected CHO cells was abolished in the presence of soluble JAM-C or the isolated D1. Furthermore, the adhesion of NCI-H522 cells to endothelial cells was significantly blocked by soluble JAM-C or the isolated D1. Thus, JAM-C undergoes a homophilic interaction via the Arg(64)Ile(65)-Glu(66) motif on the membrane-distal Ig domain of the molecule. The homophilic interaction of JAM-C can mediate tumor cell-endothelial cell interactions and may thereby be involved in the process of tumor cell metastasis. C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. Univ Giessen, Inst Clin Immunol & Transfus Med, D-35392 Giessen, Germany. RP Chavakis, T (reprint author), NCI, Expt Immunol Branch, NIH, 10 Ctr Dr,Rm 4B17, Bethesda, MD 20892 USA. EM chavakist@mail.nih.gov RI Orlova, Valeria/C-6065-2014 OI Orlova, Valeria/0000-0002-1169-2802 NR 29 TC 49 Z9 50 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 OCT 28 PY 2005 VL 280 IS 43 BP 36326 EP 36333 DI 10.1074/jbc.M505059200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 976IM UT WOS:000232726900066 PM 16118203 ER PT J AU Zhu, GZ Fujii, K Liu, Y Codrea, V Herrero, J Shaw, S AF Zhu, GZ Fujii, K Liu, Y Codrea, V Herrero, J Shaw, S TI A single pair of acidic residues in the kinase major groove mediates strong substrate preference for P-2 or P-5 arginine in the AGC, CAMK, and STE kinase families SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DEPENDENT PROTEIN-KINASE; SPECIFICITY DETERMINANTS; PHOSPHORYLATION SITE; RECOGNITION SEQUENCE; PEPTIDE SPECIFICITY; CRYSTAL-STRUCTURE; STRUCTURAL BASIS; BASIC RESIDUES; MOTIFS; IDENTIFICATION AB Most basophilic serine/threonine kinases preferentially phosphorylate substrates with Arg at P - 3 but vary greatly in additional strong preference for Arg at P - 2 or P - 5. The structural basis for P - 2 or P - 5 preference is known for two AGC kinases ( family of protein kinases A, G, and C) in which it is mediated by a single pair of acidic residues ( PEN + 1 and YEM + 1). We sought a general understanding of P - 2 and P - 5Arg preference. The strength of Arg preference at each position was assessed in 15 kinases using a new degenerate peptide library approach. Strong P - 2 or P - 5 Arg preference occurred not only in AGC kinases ( 7 of 8 studied) but also in calmodulin-dependent protein kinase (CAMK, 1 of 3) and Ste20 (STE) kinases ( 2 of 4). Analysis of sequence conservation demonstrated almost perfect correlation between ( a) strong P - 2 or P - 5 Arg preference and (b) acidic residues at both PEN + 1 and YEM + 1. Mutation of two kinases (PKC-theta and p21-activated kinase 1 (PAK1)) confirmed critical roles of both PEN + 1 and YEM + 1 residues in determining strong R-2 Arg preference. PAK kinases were unique in having exceptionally strong Arg preference at P - 2 but lacking strong Arg preference at P - 3. Preference for Arg at P - 2 was so critical to PAK recognition that PAK1 activity was virtually eliminated by mutating the PEN + 1 or YEM + 1 residues. The fact that this specific pair of acidic residues has been repeatedly and exclusively used by evolution for conferring strong Arg preference at two different substrate positions in three different kinase families implies it is uniquely well suited to mediate sufficiently good substrate binding without unduly restricting product release. C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. AxCell Biosci, Newtown, PA 18940 USA. RP Shaw, S (reprint author), NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. EM sshaw@nih.gov FU Intramural NIH HHS NR 46 TC 35 Z9 35 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 OCT 28 PY 2005 VL 280 IS 43 BP 36372 EP 36379 DI 10.1074/jbc.M505031200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 976IM UT WOS:000232726900071 PM 16131491 ER PT J AU Niiya, F Xie, XZ Lee, KS Inoue, H Miki, T AF Niiya, F Xie, XZ Lee, KS Inoue, H Miki, T TI Inhibition of cyclin-dependent kinase 1 induces cytokinesis without chromosome segregation in an ECT2 and MgcRacGAP-dependent manner SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID EXCHANGE FACTOR; LIGHT-CHAIN; CLEAVAGE FURROW; CITRON KINASE; CELL-DIVISION; MYOSIN-II; RHO; PHOSPHORYLATION; SPINDLE; COMPLEX AB Cleavage furrow formation marks the onset of cell division during early anaphase. The small GTPase RhoA and its regulators ECT2 and MgcRacGAP have been implicated in furrow ingression in mammalian cells, but the signaling upstream of these molecules remains unclear. We now show that the inhibition of cyclin-dependent kinase (Cdk) 1 is sufficient to initiate cytokinesis. When mitotically synchronized cells were treated with the Cdk-specific inhibitor BMI-1026, the initiation of cytokinesis was induced precociously before chromosomal separation. Cytokinesis was also induced by the Cdk1-specific inhibitor purvalanol A but not by Cdk2/Cdk5- or Cdk4-specific inhibitors. Consistent with initiation of precocious cytokinesis by Cdk1 inhibition, introduction of anti-Cdk1 monoclonal antibody resulted in cells with aberrant nuclei. Depolymerization of mitotic spindles by nocodazole inhibited BMI-1026-induced precocious cytokinesis. However, in the presence of a low concentration of nocodazole, BMI-1026 induced excessive membrane blebbing, which appeared to be caused by formation of ectopic cleavage furrows. Depletion of ECT2 or MgcRacGAP by RNA interference abolished both of the phenotypes ( precocious furrowing after nocodazole release and excessive blebbing in the presence of nocodazole). RNA interference of RhoA or expression of dominant-negative RhoA efficiently reduced both phenotypes. RhoA was localized at the cleavage furrow or at the necks of blebs. We propose that Cdk1 inactivation is sufficient to activate a signaling pathway leading to cytokinesis, which emanates from mitotic spindles and is regulated by ECT2, MgcRacGAP, and RhoA. Chemical induction of cytokinesis will be a valuable tool to study the initiation mechanism of cytokinesis. C1 NCI, Mol Tumor Biol Sect, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. RP Miki, T (reprint author), NCI, Mol Tumor Biol Sect, Cell Biol Lab, NIH, Bldg 37,Rm 2144,37 Convent Dr, Bethesda, MD 20892 USA. EM toru@helix.nih.gov FU Intramural NIH HHS NR 34 TC 53 Z9 54 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 OCT 28 PY 2005 VL 280 IS 43 BP 36502 EP 36509 DI 10.1074/jbc.M508007200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 976IM UT WOS:000232726900084 PM 16118207 ER PT J AU Gagnon, SJ Borbulevych, OY Davis-Harrison, RL Baxter, TK Clemens, JR Armstrong, KM Turner, RV Damirjian, M Biddison, WE Baker, BM AF Gagnon, SJ Borbulevych, OY Davis-Harrison, RL Baxter, TK Clemens, JR Armstrong, KM Turner, RV Damirjian, M Biddison, WE Baker, BM TI Unraveling a hotspot for TCR recognition on HLA-A2: Evidence against the existence of peptide-independent TCR binding determinants SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE T cell receptors; protein-protein interactions; continuum electrostatics; binding determinants; hot spots ID T-CELL-RECEPTOR; MAJOR HISTOCOMPATIBILITY COMPLEX; PROTEIN-PROTEIN INTERACTIONS; ELECTROSTATIC INTERACTIONS; CROSS-REACTIVITY; STRUCTURAL BASIS; MHC RECOGNITION; HOT-SPOTS; INTERFACES; SELECTION AB T cell receptor (TCR) recognition of peptide takes place in the context of the major histocompatibility complex (MHC) molecule, which accounts for approximately two-thirds of the peptide/MHC buried surface. Using the class 1 MHC HLA-A2 and a large panel of mutants, we have previously shown that surface mutations that disrupt TCR recognition vary with the identity of the peptide. The single exception is Lys66 on the HLA-A2 alpha 1 helix, which when mutated to alanine disrupts recognition for 93% of over 250 different T cell clones or lines, independent of which peptide is bound. Thus, Lys66 could serve as a peptide-independent TCR binding determinant. Here, we have examined the role of Lys66 in TCR recognition of HLA-A2 in detail. The structure of a peptide/HLA-A2 molecule with the K66A mutation indicates that although the mutation induces no major structural changes, it results in the exposure of a negatively charged glutamate (Glu63) underneath Lys66. Concurrent replacement of Glu63 with glutamine restores TCR binding and function for T cells specific for five different peptides presented by HLA-A2. Thus, the positive charge on Lys66 does not serve to guide all TCRs onto the HLA-A2 molecule in a manner required for productive signaling. Furthermore, electrostatic calculations indicate that Lys66 does not contribute to the stability of two TCR-peptide/HLA-A2 complexes. Our findings are consistent with the notion that each TCR arrives at a unique solution of how to bind a peptide/MHC, most strongly influenced by the chemical and structural features of the bound peptide. This would not rule out an intrinsic affinity of TCRs for MHC molecules achieved through multiple weak interactions, but for HLA-A2 the collective mutational data place limits on the role of any single MHC amino acid side-chain in driving TCR binding in a peptide-independent fashion. Published by Elsevier Ltd. C1 Univ Notre Dame, Dept Chem & Biochem, Notre Dame, IN 46556 USA. NINDS, Mol Immunol Sect, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. Univ Notre Dame, Walther Canc Res Ctr, Notre Dame, IN 46556 USA. RP Baker, BM (reprint author), Univ Notre Dame, Dept Chem & Biochem, 251 Nieuwland Sci Hall, Notre Dame, IN 46556 USA. EM bbaker2@nd.edu RI Baker, Brian/B-4584-2009 OI Baker, Brian/0000-0002-0864-0964 FU NIGMS NIH HHS [GM067079] NR 53 TC 27 Z9 28 U1 0 U2 3 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 OCT 28 PY 2005 VL 353 IS 3 BP 556 EP 573 DI 10.1016/j.jmb.2005.08.024 PG 18 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 977PO UT WOS:000232815900009 PM 16197958 ER PT J AU Yamada, T Fischle, W Sugiyama, T Allis, CD Grewal, SIS AF Yamada, T Fischle, W Sugiyama, T Allis, CD Grewal, SIS TI The nucleation and maintenance of heterochromatin by a histone deacetylase in fission yeast SO MOLECULAR CELL LA English DT Article ID H3 LYSINE-9 METHYLATION; HP1 CHROMO DOMAIN; SCHIZOSACCHAROMYCES-POMBE; EPIGENETIC CONTROL; RNAI; PROTEIN; ESTABLISHMENT; METHYLTRANSFERASES; RECOMBINATION; TRANSCRIPTION AB Posttranslational modifications of histories play an essential role in heterochromatin assembly. Whereas the role of Clr4/Suv39h-mediated methylation of histone H3 at lysine 9 (H3K9) in heterochromatin assembly is well studied, the exact function of histone deacetylases (HDACs) in this process is unclear. We show that Clr3, a fission yeast homolog of mammalian class II HDACs, acts in a distinct pathway parallel to RNAi-directed heterochromatin nucleation to recruit Clr4 and mediate H3K9 methylation at the silent mating-type region and centromeres. At the mat locus, Clr3 is recruited at a specific site through a mechanism involving ATF/CREB family proteins. Once recruited, Clr3 spreads across the 20 kb silenced domain that requires its own HDAC activity and heterochromatin proteins including Swi6/HP1. We also demonstrate that Clr3 contributes to heterochromatin maintenance by stabilizing H3K9 trimethylation and by preventing histone modifications associated with active transcription, and that it limits RNA polymerase II accessibility to naturally silenced repeats at heterochromatin domains. C1 NCI, Mol Cell Biol Lab, NIH, Bethesda, MD 20892 USA. Rockefeller Univ, Lab Chromatin Biol, New York, NY 10021 USA. RP Grewal, SIS (reprint author), NCI, Mol Cell Biol Lab, NIH, Bethesda, MD 20892 USA. EM grewals@mail.nih.gov OI Sugiyama, Tomoyasu/0000-0001-5704-6606 FU Intramural NIH HHS NR 51 TC 131 Z9 136 U1 0 U2 5 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD OCT 28 PY 2005 VL 20 IS 2 BP 173 EP 185 DI 10.1016/j.molcel.2005.10.002 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 982HA UT WOS:000233147500004 PM 16246721 ER PT J AU Altshuler, D Brooks, LD Chakravarti, A Collins, FS Daly, MJ Donnelly, P Gibbs, RA Belmont, JW Boudreau, A Leal, SM Hardenbol, P Pasternak, S Wheeler, DA Willis, TD Yu, FL Yang, HM Zeng, CQ Gao, Y Hu, HR Hu, WT Li, CH Lin, W Liu, SQ Pan, H Tang, XL Wang, J Wang, W Yu, J Zhang, B Zhang, QR Zhao, HB Zhao, H Zhou, J Gabriel, SB Barry, R Blumenstiel, B Camargo, A Defelice, M Faggart, M Goyette, M Gupta, S Moore, J Nguyen, H Onofrio, RC Parkin, M Roy, J Stahl, E Winchester, E Ziaugra, L Shen, Y Yao, ZJ Huang, W Chu, X He, YG Jin, L Liu, YF Shen, YY Sun, WW Wang, HF Wang, Y Wang, Y Wang, Y Xiong, XY Xu, L Waye, MMY Tsui, SKW Xue, H Wong, JTF Galver, ILM Fan, JB Murray, SS Oliphant, AR Chee, MS Montpetit, A Chagnon, F Ferretti, V Leboeuf, M Olivier, JF Phillips, MS Roumy, S Sallee, C Verner, A Hudson, TJ Frazer, KA Ballinger, DG Cox, DR Hinds, DA Stuve, LL Kwok, PY Cai, DM Koboldt, DC Miller, RD Pawlikowska, L Taillon-Miller, P Xiao, M Tsui, LC Mak, W Sham, PC Song, YQ Tam, PKH Nakamura, Y Kawaguchi, T Kitamoto, T Morizono, T Nagashima, A Ohnishi, Y Sekine, A Tanaka, T Tsunoda, T Deloukas, P Bird, CP Delgado, M Dermitzakis, ET Gwilliam, R Hunt, S Morrison, J Powell, D Stranger, BE Whittaker, P Bentley, DR Daly, MJ de Bakker, PIW Barrett, J Fry, B Maller, J McCarroll, S Patterson, N Pe'er, I Purcell, S Richter, DJ Sabeti, P Saxena, R Schaffner, SF Varilly, P Stein, LD Krishnan, L Smith, AV Thorisson, GA Chen, PE Cutler, DJ Kashuk, CS Lin, S Abecasis, GR Guan, WH Munro, HM Qin, ZHS Thomas, DJ McVean, G Bottolo, L Eyheramendy, S Freeman, C Marchini, J Myers, S Spencer, C Stephens, M Cardon, LR Clarke, G Evans, DM Morris, AP Weir, BS Tsunoda, T Mullikin, JC Sherry, ST Feolo, M Zhang, HC Zeng, CQ Zhao, H Matsuda, I Fukushima, Y Macer, DR Suda, E Rotimi, CN Adebamowo, CA Ajayi, I Aniagwu, T Marshall, PA Nkwodimmah, C Royal, CDM Leppert, MF Dixon, M Peiffer, A Qiu, RZ Kent, A Kato, K Niikawa, N Adewole, IF Knoppers, BM Foster, MW Clayton, EW Muzny, D Nazareth, L Sodergren, E Weinstock, GM Wheeler, DA Yakub, I Gabriel, SB Richter, DJ Ziaugra, L Birren, BW Wilson, RK Fulton, LL Rogers, J Burton, J Carter, NP Clee, CM Griffiths, M Jones, MC McLay, K Plumb, RW Ross, MT Sims, SK Willey, DL Chen, Z Han, H Kang, L Godbout, M Wallenburg, JC Archeveque, PL Bellemare, G Saeki, K Wang, HG An, DC Fu, HB Li, Q Wang, Z Wang, RW Holden, AL Brooks, LD McEwen, JE Bird, CR Guyer, MS Nailer, PJ Wang, VO Peterson, JL Shi, M Spiegel, J Sung, LM Witonsky, J Zacharia, LF Kennedy, K Jamieson, R Stewart, J AF Altshuler, D Brooks, LD Chakravarti, A Collins, FS Daly, MJ Donnelly, P Gibbs, RA Belmont, JW Boudreau, A Leal, SM Hardenbol, P Pasternak, S Wheeler, DA Willis, TD Yu, FL Yang, HM Zeng, CQ Gao, Y Hu, HR Hu, WT Li, CH Lin, W Liu, SQ Pan, H Tang, XL Wang, J Wang, W Yu, J Zhang, B Zhang, QR Zhao, HB Zhao, H Zhou, J Gabriel, SB Barry, R Blumenstiel, B Camargo, A Defelice, M Faggart, M Goyette, M Gupta, S Moore, J Nguyen, H Onofrio, RC Parkin, M Roy, J Stahl, E Winchester, E Ziaugra, L Shen, Y Yao, ZJ Huang, W Chu, X He, YG Jin, L Liu, YF Shen, YY Sun, WW Wang, HF Wang, Y Wang, Y Wang, Y Xiong, XY Xu, L Waye, MMY Tsui, SKW Xue, H Wong, JTF Galver, ILM Fan, JB Murray, SS Oliphant, AR Chee, MS Montpetit, A Chagnon, F Ferretti, V Leboeuf, M Olivier, JF Phillips, MS Roumy, S Sallee, C Verner, A Hudson, TJ Frazer, KA Ballinger, DG Cox, DR Hinds, DA Stuve, LL Kwok, PY Cai, DM Koboldt, DC Miller, RD Pawlikowska, L Taillon-Miller, P Xiao, M Tsui, LC Mak, W Sham, PC Song, YQ Tam, PKH Nakamura, Y Kawaguchi, T Kitamoto, T Morizono, T Nagashima, A Ohnishi, Y Sekine, A Tanaka, T Tsunoda, T Deloukas, P Bird, CP Delgado, M Dermitzakis, ET Gwilliam, R Hunt, S Morrison, J Powell, D Stranger, BE Whittaker, P Bentley, DR Daly, MJ de Bakker, PIW Barrett, J Fry, B Maller, J McCarroll, S Patterson, N Pe'er, I Purcell, S Richter, DJ Sabeti, P Saxena, R Schaffner, SF Varilly, P Stein, LD Krishnan, L Smith, AV Thorisson, GA Chen, PE Cutler, DJ Kashuk, CS Lin, S Abecasis, GR Guan, WH Munro, HM Qin, ZHS Thomas, DJ McVean, G Bottolo, L Eyheramendy, S Freeman, C Marchini, J Myers, S Spencer, C Stephens, M Cardon, LR Clarke, G Evans, DM Morris, AP Weir, BS Tsunoda, T Mullikin, JC Sherry, ST Feolo, M Zhang, HC Zeng, CQ Zhao, H Matsuda, I Fukushima, Y Macer, DR Suda, E Rotimi, CN Adebamowo, CA Ajayi, I Aniagwu, T Marshall, PA Nkwodimmah, C Royal, CDM Leppert, MF Dixon, M Peiffer, A Qiu, RZ Kent, A Kato, K Niikawa, N Adewole, IF Knoppers, BM Foster, MW Clayton, EW Muzny, D Nazareth, L Sodergren, E Weinstock, GM Wheeler, DA Yakub, I Gabriel, SB Richter, DJ Ziaugra, L Birren, BW Wilson, RK Fulton, LL Rogers, J Burton, J Carter, NP Clee, CM Griffiths, M Jones, MC McLay, K Plumb, RW Ross, MT Sims, SK Willey, DL Chen, Z Han, H Kang, L Godbout, M Wallenburg, JC Archeveque, PL Bellemare, G Saeki, K Wang, HG An, DC Fu, HB Li, Q Wang, Z Wang, RW Holden, AL Brooks, LD McEwen, JE Bird, CR Guyer, MS Nailer, PJ Wang, VO Peterson, JL Shi, M Spiegel, J Sung, LM Witonsky, J Zacharia, LF Kennedy, K Jamieson, R Stewart, J CA Int HapMap Consortium TI A haplotype map of the human genome SO NATURE LA English DT Review ID SINGLE-NUCLEOTIDE POLYMORPHISM; RECENT POSITIVE SELECTION; FACTOR-H POLYMORPHISM; LINKAGE-DISEQUILIBRIUM; MACULAR DEGENERATION; RECOMBINATION RATES; HUMAN-POPULATIONS; SEGMENTAL DUPLICATIONS; MEIOTIC RECOMBINATION; TYROSINE-PHOSPHATASE AB Inherited genetic variation has a critical but as yet largely uncharacterized role in human disease. Here we report a public database of common variation in the human genome: more than one million single nucleotide polymorphisms ( SNPs) for which accurate and complete genotypes have been obtained in 269 DNA samples from four populations, including ten 500-kilobase regions in which essentially all information about common DNA variation has been extracted. These data document the generality of recombination hotspots, a block-like structure of linkage disequilibrium and low haplotype diversity, leading to substantial correlations of SNPs with many of their neighbours. We show how the HapMap resource can guide the design and analysis of genetic association studies, shed light on structural variation and recombination, and identify loci that may have been subject to natural selection during human evolution. C1 Harvard Univ, Broad Inst, Cambridge, MA 02139 USA. MIT, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Simches Res Ctr, Boston, MA 02114 USA. Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA. Baylor Coll Med, Human Genome Sequencing Ctr, Dept Mol & Human Genet, Houston, TX 77030 USA. ParAllele Biosci Inc, San Francisco, CA 94080 USA. Chinese Acad Sci, Beijing Genom Inst, Beijing 100300, Peoples R China. Chinese Natl Human Genome Ctr, Beijing Econ Technol Dev Area, Beijing 100176, Peoples R China. Chinese Natl Human Genome Ctr Shanghai, Shanghai 201203, Peoples R China. Chinese Univ Hong Kong, Dept Biochem, Croucher Lab Human Genom, Shatin, Hong Kong, Peoples R China. Hong Kong Univ Sci & Technol, Dept Biochem, Kowloon, Hong Kong, Peoples R China. Illumina, San Diego, CA 92121 USA. Prognosys Biosci Inc, San Diego, CA 92121 USA. McGill Univ, Montreal, PQ H3A 1A4, Canada. Genome Quebec Innovat Ctr, Montreal, PQ H3A 1A4, Canada. Univ Montreal, Publ Law Res Ctr CRDP, Montreal, PQ H3C 3J7, Canada. Perlegen Sci Inc, Mountain View, CA 94043 USA. Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA. Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA. Univ Hong Kong, Genome Res Ctr, Pokfulam, Hong Kong, Peoples R China. Univ Tokyo, Inst Med Sci, Minato Ku, Tokyo 1088639, Japan. RIKEN, SNP Res Ctr, Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan. Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England. Solexa Ltd, Saffron Walden CB10 1XL, Essex, England. Cold Spring Harbor Lab, New York, NY 11724 USA. Univ Michigan, Ctr Stat Genet, Dept Biostat, Ann Arbor, MI 48109 USA. Univ Calif Santa Cruz, Ctr Biomol Sci & Engn, Santa Cruz, CA 95064 USA. Univ Washington, Dept Stat, Washington, DC 98195 USA. Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England. N Carolina State Univ, Bioinformat Res Ctr, Raleigh, NC 27695 USA. Natl Human Genome Res Inst, US Natl Inst Hlth, Bethesda, MD 20892 USA. US Natl Inst Hlth, Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. Beijing Normal Univ, Beijing 100875, Peoples R China. Hlth Sci Univ Hokkaido, Ishikari, Hokkaido, Japan. Shinshu Univ, Sch Med, Dept Med Genet, Matsumoto, Nagano 3908621, Japan. UNESCO, Bangkok 10110, Thailand. Univ Tsukuba, Eubios Eth Inst, Tsukuba 3058691, Japan. Howard Univ, Natl Human Genome Ctr, Washington, DC 20059 USA. Univ Ibadan, Coll Med, Ibadan, Oyo State, Nigeria. Case Western Reserve Univ, Sch Med, Dept Bioeth, Cleveland, OH 44106 USA. Univ Utah, Eccles Inst Human Genet, Dept Human Genet, Salt Lake City, UT 84112 USA. Chinese Acad Social Sci, Ctr Appl Eth, Beijing 100054, Peoples R China. Genet Interest Grp, London N1 3QP, England. Kyoto Univ, Inst Res Humanities, Sakyo Ku, Kyoto 6068501, Japan. Grad Sch Biostudies, Sakyo Ku, Kyoto 6068501, Japan. Nagasaki Univ, Grad Sch Biomed Sci, Dept Human Genet, Nagasaki 8528523, Japan. Univ Oklahoma, Dept Anthropol, Norman, OK 73019 USA. Vanderbilt Univ, Ctr Genet & Hlth Policy, Nashville, TN 37232 USA. Wellcome Trust Res Labs, London NW1 2BE, England. Washington Univ, Sch Med, Genome Sequencing Ctr, St Louis, MO 63108 USA. Chinese Acad Sci, Beijing 100864, Peoples R China. Genome Canada, Ottawa, ON K2P 1P1, Canada. McGill Univ, Off Technol Transfer, Montreal, PQ H3A 2A7, Canada. Genome Quebec, Montreal, PQ H3B 1S6, Canada. Minist Educ Culture Sports Sci & Technol, Chiyoda Ku, Tokyo 1008959, Japan. Minist Sci & Technol, Beijing 100862, Peoples R China. Human Genet Resource Adm China, Beijing 100081, Peoples R China. SNP Consortium, Deerfield, IL 60015 USA. Novartis Pharmaceut, Biomarker Dev, E Hanover, NJ 07936 USA. US Natl Inst Hlth, Off Technol Transfer, Rockville, MD 20852 USA. Univ Maryland, Sch Law, Baltimore, MD 21201 USA. Frost & Sullivan, Palo Alto, CA 94303 USA. RP Altshuler, D (reprint author), Harvard Univ, Broad Inst, 1 Kendall Sq, Cambridge, MA 02139 USA. EM altshuler@molbio.mgh.harvard.edu; donnelly@stats.ox.ac.uk RI Varilly, Patrick/C-8118-2013; Evans, David/H-6325-2013; de Bakker, Paul/B-8730-2009; Kwok, Pui-Yan/F-7725-2014; Tsunoda, Tatsuhiko/K-2061-2014; Waye 韋妙宜教授, Mary Miu Yee /A-9674-2008; Tsui, Stephen Kwok-Wing/E-4385-2015; Tanaka, Toshihiro/J-9310-2014; Smith, Albert/K-5150-2015; Jin, Li/C-1468-2009; Tam, Paul/C-4405-2009; Deloukas, Panos/B-2922-2013; Dermitzakis, Emmanouil/B-7687-2013; Abecasis, Goncalo/B-7840-2010; Thorisson, Gudmundur/E-7359-2010; Altshuler, David/A-4476-2009; Tsui, Lap-chee/A-1081-2010; Schaffner, Stephen/D-1189-2011; Song, You-Qiang/E-5207-2011; Song, You-qiang/C-4401-2009; Qin, Zhaohui/E-8196-2011; 郑, 征/C-8514-2011 OI Adebamowo, Clement/0000-0002-6571-2880; Abecasis, Goncalo/0000-0003-1509-1825; Xue, Hong/0000-0002-8133-9828; Stranger, Barbara/0000-0001-9021-7331; He, Yungang/0000-0002-2931-2871; Evans, David/0000-0003-0663-4621; Varilly, Patrick/0000-0003-4619-8174; de Bakker, Paul/0000-0001-7735-7858; Kwok, Pui-Yan/0000-0002-5087-3059; Waye 韋妙宜教授, Mary Miu Yee /0000-0002-2582-4917; Tsui, Stephen Kwok-Wing/0000-0003-0686-4259; Tanaka, Toshihiro/0000-0001-6201-9784; Smith, Albert/0000-0003-1942-5845; Belmont, John/0000-0001-7409-3578; Hudson, Thomas/0000-0002-1376-4849; Jin, Li/0000-0002-4546-2415; Deloukas, Panos/0000-0001-9251-070X; Thorisson, Gudmundur/0000-0001-5635-1860; Altshuler, David/0000-0002-7250-4107; Qin, Zhaohui/0000-0002-1583-146X; NR 103 TC 3469 Z9 3579 U1 29 U2 364 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD OCT 27 PY 2005 VL 437 IS 7063 BP 1299 EP 1320 DI 10.1038/nature04226 PG 22 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 977UQ UT WOS:000232829100044 ER PT J AU Berry, DA Cronin, KA Plevritis, SK Fryback, DG Clarke, L Zelen, M Mandelblatt, JS Yakovlev, AY Habbema, JDF Feuer, EJ AF Berry, DA Cronin, KA Plevritis, SK Fryback, DG Clarke, L Zelen, M Mandelblatt, JS Yakovlev, AY Habbema, JDF Feuer, EJ CA CISNET Collaborators TI Effect of screening and adjuvant therapy on mortality from breast cancer SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID RANDOMIZED-TRIALS; UNITED-STATES; SOCIETY GUIDELINES; FOLLOW-UP; MAMMOGRAPHY; TAMOXIFEN; PROGRESS AB BACKGROUND: We used modeling techniques to assess the relative and absolute contributions of screening mammography and adjuvant treatment to the reduction in breast-cancer mortality in the United States from 1975 to 2000. METHODS: A consortium of investigators developed seven independent statistical models of breast-cancer incidence and mortality. All seven groups used the same sources to obtain data on the use of screening mammography, adjuvant treatment, and benefits of treatment with respect to the rate of death from breast cancer. RESULTS: The proportion of the total reduction in the rate of death from breast cancer attributed to screening varied in the seven models from 28 to 65 percent (median, 46 percent), with adjuvant treatment contributing the rest. The variability across models in the absolute contribution of screening was larger than it was for treatment, reflecting the greater uncertainty associated with estimating the benefit of screening. CONCLUSIONS: Seven statistical models showed that both screening mammography and treatment have helped reduce the rate of death from breast cancer in the United States. C1 Univ Texas, MD Anderson Canc Ctr, Dept Biostat & Appl Math, Unit 447, Houston, TX 77030 USA. NCI, Bethesda, MD 20892 USA. Stanford Univ, Stanford, CA 94305 USA. Univ Wisconsin, Madison, WI USA. Cornerstone Syst, Lynden, WA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Georgetown Univ, Washington, DC USA. Univ Rochester, Rochester, NY USA. Erasmus Univ, Med Ctr, Rotterdam, Netherlands. RP Berry, DA (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Biostat & Appl Math, Unit 447, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM dberry@mdanderson.org RI Boer, Rob/E-6473-2015 OI Boer, Rob/0000-0003-0680-001X FU NCI NIH HHS [U01CA69976, CA88177, CA88202, CA88211, CA88248, CA88270, CA88278, CA88283, U01CA63731, U01CA63736, U01CA63740, U01CA70013, U01CA70040, U01CA86076, U01CA86082] NR 27 TC 1113 Z9 1146 U1 6 U2 79 PU MASSACHUSETTS MEDICAL SOC 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 OCT 27 PY 2005 VL 353 IS 17 BP 1784 EP 1792 DI 10.1056/NEJMoa050518 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 977OL UT WOS:000232813000006 PM 16251534 ER PT J AU Uddin, S Hussain, AR Manogaran, PS Al-Hussein, K Platanias, LC Gutierrez, MI Bhatia, KG AF Uddin, S Hussain, AR Manogaran, PS Al-Hussein, K Platanias, LC Gutierrez, MI Bhatia, KG TI Curcumin suppresses growth and induces apoptosis in primary effusion lymphoma SO ONCOGENE LA English DT Article DE PEL; curcumin; cell death; NHL therapy ID FACTOR-KAPPA-B; MULTIPLE-MYELOMA CELLS; CYTOCHROME-C RELEASE; TRANSCRIPTION FACTOR; SIGNAL TRANSDUCER; DIETARY CURCUMIN; IN-VITRO; ACTIVATION; INHIBITION; KINASE AB The mechanisms that regulate induction of the antiapoptotic state and mitogenic signals in primary effusion lymphoma (PEL) are not well known. In efforts to identify novel approaches to block the proliferation of PEL cells, we found that curcumin (diferuloylmethane), a natural compound isolated from the plant Curcuma Ionga, inhibits cell proliferation and induces apoptosis in a dose dependent manner in several PEL cell lines. Such effects of curcumin appear to result from suppression of the constitutively active STAT3 through inhibition of Janus kinase 1 (JAK1). Our data also demonstrate that curcumin induces loss of mitochondrial membrane potential with subsequent release of cytochrome c and activation of caspase-3, followed by polyadenosin-5'-diphosphate-ribose polymerase (PARP) cleavage. Altogether, our findings suggest a novel function for curcumin, acting as a suppressor of JAK-1 and STAT3 activation in PEL cells, leading to inhibition of proliferation and induction of caspase-dependent apoptosis. Therefore, curcumin may have a future therapeutic role in PEL and possibly other malignancies with constitutive activation of STAT3. C1 King Fahad Natl Ctr Childrens Canc & Res, Riyadh 11211, Saudi Arabia. King Faisal Specialist Hosp & Res Ctr, BMR, Riyadh 11211, Saudi Arabia. Northwestern Univ, Sch Med, Div Hematol Oncol, Robert H Lurie Comprehens Canc Ctr, Chicago, IL USA. NCI, Canc Diagnosis Program, Rockville, MD USA. RP Uddin, S (reprint author), King Fahad Natl Ctr Childrens Canc & Res, MBC98-16,POB 3354, Riyadh 11211, Saudi Arabia. EM Shahab@kfshrc.edu.sa; Bhatiak@mail.nih.gov NR 44 TC 78 Z9 79 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD OCT 27 PY 2005 VL 24 IS 47 BP 7022 EP 7030 DI 10.1038/sj.onc.1208864 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 977WC UT WOS:000232833200004 PM 16044161 ER PT J AU Kamrava, M Simpkins, F Alejandro, E Michener, C Meltzer, E Kohn, EC AF Kamrava, M Simpkins, F Alejandro, E Michener, C Meltzer, E Kohn, EC TI Lysophosphatidic acid and endothelin-induced proliferation of ovarian cancer cell lines is mitigated by neutralization of granulin-epithelin precursor (GEP), a prosurvival factor for ovarian cancer SO ONCOGENE LA English DT Article DE ovarian cancer; progranulin; apoptosis; EPAC; signaling ID DEPENDENT PROTEIN-KINASE; GROWTH-FACTOR RECEPTOR; CARCINOMA CELLS; COUPLED RECEPTORS; CYCLIC-AMP; SIGNALING PATHWAYS; ALPHA SUBUNIT; FACTOR PCDGF; ACTIVATION; EPAC AB Granulin-epithelin precursor (GEP/progranulin) is an autocrine growth factor for ovarian cancer. We examined the production and function of GEP and report that: (1) GEP production is regulated by endothelin (ET-1), lysophosphatidic acid (LPA), and cAMP; (2) cAMP signals GEP production through exchange protein activated by cAMP (EPAC); (3) ET-1 and cAMP/EPAC induce GEP through ERK1/2; and (4) neutralization of GEP results in apoptosis. Exposure of HEY-A8 and OVCAR3 ovarian cancer cells to LPA and ET-1 yielded GEP production and secretion in a dose- and time-dependent fashion; neither stimulated significant concentrations of cAMP directly. Stimulation of cAMP production with pertussis and cholera toxin, or forskolin induced GEP in a PKA-independent fashion. EPAC, an intracellular cAMP receptor, is activated specifically by the cAMP analog, 8-CPT-2'-O-Me-cAMP (8-CPT); 8-CPT treatment stimulated GEP production and secretion. The MEK inhibitor, U0126, abrogated GEP production in response to ET-1 and 8-CPT, confirming involvement of MAPK. A partial inhibition of basal and stimulated GEP production was observed when cells were treated with a internal calcium chelator, BAPTA. Neutralizing anti-GEP antibody reversed basal as well as LPA, ET-1 and 8CPT-induced ovarian cancer cell growth and induced apoptosis as demonstrated by caspase-3 and PARP cleavage, DNA fragmentation, and nuclear condensation. These results indicate that GEP is a growth and survival factor for ovarian cancer, induced by LPA and ET-1 and cAMP/EPAC through ERK1/2. C1 NCI, Pathol Lab, Mol Signaling Sect, Canc Res Ctr, Bethesda, MD 20892 USA. NIH, Howard Hughes Med Inst, Res Scholars Program, Bethesda, MD 20892 USA. RP Kohn, EC (reprint author), NCI, Pathol Lab, Mol Signaling Sect, Canc Res Ctr, 10 Ctr Dr MSC 1500, Bethesda, MD 20892 USA. EM ek1b@nih.gov OI Alejandro, Emilyn/0000-0002-7941-8439 NR 47 TC 45 Z9 49 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD OCT 27 PY 2005 VL 24 IS 47 BP 7084 EP 7093 DI 10.1038/sj.onc.1208857 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 977WC UT WOS:000232833200010 PM 16044162 ER PT J AU Kirk, AD Mannon, RB Kleiner, DE Swanson, JS Kampen, RL Cendales, LK Elster, EA Wakefield, T Chamberlain, C Hoffmann, SC Hale, DA AF Kirk, AD Mannon, RB Kleiner, DE Swanson, JS Kampen, RL Cendales, LK Elster, EA Wakefield, T Chamberlain, C Hoffmann, SC Hale, DA TI Results from a human renal allograft tolerance trial evaluating T-cell depletion with alemtuzumab combined with deoxyspergualin SO TRANSPLANTATION LA English DT Article DE alemtuzumab; deoxyspergualin; immunosuppression; rejection; tolerance; transplantation ID KIDNEY-TRANSPLANTATION; HEART ALLOGRAFTS; PANCREAS-KIDNEY; INDUCTION; MONOTHERAPY; IMMUNOSUPPRESSION; UNRESPONSIVENESS; PERITRANSPLANT; IMMUNOTOXIN; CAMPATH-1H AB Background. Perioperative lymphocyte depletion induces allograft tolerance in some animal models, but in humans has only been shown to reduce immunosuppressive requirements. Without maintenance immunosuppression, depleted human renal allograft recipients experience rejection characterized by infiltration of the allograft with monocytes and macrophages. T-cell depletion combined with a brief course of deoxyspergualin (DSG), a drug with inhibitory effects on monocytes and macrophages, induces tolerance in nonhuman primates. We therefore performed a trial to determine if lymphocyte depletion with alemtuzumab combined with DSG would induce tolerance in humans. Methods. Five recipients of live donor kidneys were treated perioperatively with alemtuzumab and DSG and followed postoperatively without maintenance immunosuppression. Patients were evaluated clinically, by flow cytometry, and by protocol biopsies analyzed immunohistochemically and with real-time polymerase chain reaction. Results were compared to previously studied patients receiving alemtuzumab alone or standard immunosuppression. Results. Despite profound T-cell depletion and therapeutic DSG dosing, all alemtuzumab/DSG patients developed reversible rejection that was similar in timing, histology, and transcriptional profile to that seen in patients treated with alemtuzumab alone. Chemokine expression was marked prior to and during rejections. Conclusions. We conclude that treatment with alemtuzumab and DSG does not induce tolerance in humans. Chemokine production may not be adequately suppressed using this approach. C1 NIDDKD, Transplantat Branch, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. Walter Reed Army Med Ctr, Organ Transplant Serv, Washington, DC 20307 USA. RP Kirk, AD (reprint author), Room 5-5752,Bldg 10,Ctr Dr, Bethesda, MD 20892 USA. EM allank@intra.niddk.nih.gov RI Kirk, Allan/B-6905-2012; OI Kleiner, David/0000-0003-3442-4453 NR 20 TC 88 Z9 92 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD OCT 27 PY 2005 VL 80 IS 8 BP 1051 EP 1059 DI 10.1097/01.tp.0000174341.49741.8f PG 9 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 985KF UT WOS:000233375600009 PM 16278585 ER PT J AU Barton, JH Emanuel, EJ AF Barton, JH Emanuel, EJ TI The patents-based pharmaceutical development process: Rationale, problems, and potential reforms SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID DRUG DEVELOPMENT; MARKET; INNOVATION; MEDICINES; INDUSTRY; TRIPS AB The pharmaceutical industry is facing substantial criticism from many directions, including financial barriers to access to drugs in both developed and developing countries, high profits, spending on advertising and marketing, and other issues. Underlying these criticisms are fundamental questions about the value of the current patent-based drug development system. Six major problems with the patent system are (1) recovery of research costs by patent monopoly reduces access to drugs; (2) market demand rather than health needs determines research priorities; (3) resources between research and marketing are misallocated; (4) the market for drugs has inherent market failures; (5) overall investment in drug research and development is too low, compared with profits; and (6) the existing system discriminates against US patients. Potential solutions fall into 3 categories: change in drug pricing through either price controls or tiered pricing; change in drug industry structure through a "buy-out" pricing system or with the public sector acting as exclusive research funder; and change in development incentives through a disease burden incentive system, orphan drug approaches, or requiring new drugs to demonstrate improvement over existing products prior to US Food and Drug Administration approval. We recommend 4 complementary reforms: (1) having no requirement to test new drug products against existing products prior to approval but requiring rigorous comparative postapproval testing; (2) international tiered pricing and systematic safeguards to prevent flow-back; (3) increased government-funded research and buy-out for select conditions; and (4) targeted experiments using other approaches for health conditions in which there has been little progress and innovation over the last few decades. C1 NIH, Dept Clin Bioeth, Ctr Clin, Bethesda, MD 20892 USA. Stanford Univ, Sch Law, Stanford, CA 94305 USA. RP Emanuel, EJ (reprint author), NIH, Dept Clin Bioeth, Ctr Clin, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM eemanuel@nih.gov NR 36 TC 50 Z9 52 U1 2 U2 12 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 OCT 26 PY 2005 VL 294 IS 16 BP 2075 EP 2082 DI 10.1001/jama.294.16.2075 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 977CB UT WOS:000232778900028 PM 16249422 ER PT J AU Zuna, RE Wang, SS Rosenthal, DL Jeronimo, J Schiffman, M Solomon, D AF Zuna, RE Wang, SS Rosenthal, DL Jeronimo, J Schiffman, M Solomon, D CA ALTS Grp TI Determinants of human papillomavirus-negative, low-grade squamous intralepithelial lesions in the Atypical Squamous Cells of Undetermined Significance/low-grade squamous intraepithelial lesions Triage Study (ALTS) SO CANCER CYTOPATHOLOGY LA English DT Article DE human papillomavirus; Hybrid Capture 2; polymerase chain reaction; low-grade squamous intraepithelial lesions; cervical intraepithelial neoplasia ID ASCUS-LSIL TRIAGE; CERVICAL CYTOLOGY; RANDOMIZED-TRIAL; BETHESDA SYSTEM; WOMEN; PAPANICOLAOU; CANCER; REPRODUCIBILITY; CLASSIFICATION; MANAGEMENT AB BACKGROUND. Although low-grade squamous intraepithelial lesions (LSIL) most often are the result of infection by human papillomaviruses (HPV), a small proportion of women with LSIL have negative HPV tests. Using the Atypical Squamous Cells of Undetermined Significance/LSIL Triage Study (ALTS) population, the authors evaluated the significance of HPV-negative LSIL. METHODS. Women with cytologic interpretations of LSIL by referral Papanicolaou (Pap) tests or enrollment ThinPrep tests (range, 1195-1476 women, depending on the specimen type and the reviewer) had HPV testing performed by both Hybrid Capture 2 and polymerase chain reaction (PCR)-based linear array for 27 HPV types. RESULTS. Using 4 independent cytologic definitions of LSIL, only 3-11% of women with LSIL were found to have HPV-negative results on both HPV tests. The demographic characteristics of women with HPV-negative LSIL were consistent with those of a low-risk population; many were age > 35 years, and many reported no or only 1 recent sexual partner. The absolute risk of a histologic diagnosis of cervical intraepithelial neoplasia (CIN) Grade 3/carcinoma during the 2-year trial was lower for women with HPV-negative LSIL (range, 2-4%) compared with the absolute risks for oncogenic HPV-positive women with LSIL (range, 13-19%). However, at the next 6-month follow-up visit, 12%-32% of the women with HPV-negative LSIL had a positive HPV test. Finally, visual inspection of cervigrams demonstrated a clear association between a larger os and negative HPV test results compared with women who had HPV-positive LSIL. This may have influenced HPV sample adequacy. CONCLUSIONS. Based on the ALTS data, the authors found no evidence to support the existence of HPV-negative LSIL as a distinct biologic entity related to the risk of cervical carcinoma. Such results appear to represent cytologic misinterpretations or falsely negative HPV tests. C1 Univ Oklahoma, Hlth Sci Ctr, Dept Pathol, Oklahoma City, OK 73104 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. RP Zuna, RE (reprint author), Univ Oklahoma, Hlth Sci Ctr, Dept Pathol, BMSB 451, Oklahoma City, OK 73104 USA. EM rosemary-zuna@ouhsc.edu FU NCI NIH HHS [CN-55153, CN-55155, CN-55157, CN-55159, CN-55105, CN-55154, CN-55156, CN-55158] NR 23 TC 21 Z9 21 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD OCT 25 PY 2005 VL 105 IS 5 BP 253 EP 262 DI 10.1002/cncr.21232 PG 10 WC Oncology; Pathology SC Oncology; Pathology GA 972SU UT WOS:000232474300001 PM 15991244 ER PT J AU Ashikaga, H Kellman, P Mickelsen, SR McVeigh, ER AF Ashikaga, H Kellman, P Mickelsen, SR McVeigh, ER TI Simple and rapid quantification of mechanical dyssynchrony for cardiac resynchronization therapy SO CIRCULATION LA English DT Meeting Abstract CT 78th Annual Scientific Session of the American-Heart-Association CY NOV 13-16, 2005 CL Dallas, TX SP Amer Heart Assoc C1 NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU S MA 3525 BP U820 EP U820 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956405193 ER PT J AU Aviles, RJ Brennan, ML Katz, R Mann, S Tracy, RP Psaty, BM AF Aviles, RJ Brennan, ML Katz, R Mann, S Tracy, RP Psaty, BM TI Myeloperoxidase (MPO) modulates risk for developing congestive heart failure (CHF) SO CIRCULATION LA English DT Meeting Abstract CT 78th Annual Scientific Session of the American-Heart-Association CY NOV 13-16, 2005 CL Dallas, TX SP Amer Heart Assoc C1 NHLBI, Bethesda, MD 20892 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Univ Washington, Seattle, WA 98195 USA. Univ Vermont, Burlington, VT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU S MA 3382 BP U788 EP U788 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956405050 ER EF