FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Koh, C Heller, T Haynes-Williams, V Hara, K Feld, J Rotman, Y Ghany, MG Liang, TJ Hoofnagle, JH AF Koh, Christopher Heller, Theo Haynes-Williams, Vanessa Hara, Koji Feld, Jordan Rotman, Yaron Ghany, Marc G. Liang, T. Jake Hoofnagle, Jay H. TI CLINICAL, VIROLOGICAL, BIOCHEMICAL OUTCOMES AFTER 20 YEARS OF SUSTAINED VIROLOGICAL RESPONSE (SVR) IN CHRONIC HEPATITIS C: THE NIH EXPERIENCE SO HEPATOLOGY LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 29-NOV 02, 2010 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Koh, Christopher; Heller, Theo; Haynes-Williams, Vanessa; Hara, Koji; Feld, Jordan; Rotman, Yaron; Ghany, Marc G.; Liang, T. Jake; Hoofnagle, Jay H.] NIDDK, Liver Dis Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2010 VL 52 IS 4 SU S MA 228 BP 436A EP 437A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 740EY UT WOS:000288775600234 ER PT J AU Feld, JJ Li, QS Hu, ZY Cherepanov, VA Thomas, E Liang, TJ AF Feld, Jordan J. Li, Qisheng Hu, Zongyi Cherepanov, Vera A. Thomas, Emmanuel Liang, T. Jake TI IDENTIFICATION OF ANTI-HEPATITIS C VIRUS INTERFERON-STIMULATED GENES USING A FUNCTIONAL GENOMICS APPROACH SO HEPATOLOGY LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 29-NOV 02, 2010 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Feld, Jordan J.; Cherepanov, Vera A.] Univ Toronto, Toronto Western Liver Ctr, Toronto, ON, Canada. [Feld, Jordan J.; Li, Qisheng; Hu, Zongyi; Thomas, Emmanuel; Liang, T. Jake] NIDDK, Liver Dis Branch, NIH, Bethesda, MD USA. RI Li, Qisheng/K-1909-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2010 VL 52 IS 4 SU S MA 244 BP 445A EP 445A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 740EY UT WOS:000288775600250 ER PT J AU Speliotes, EK Yerges-Armstrong, LM Wu, J Hernaez, R Kim, LJ Palmer, C Harris, TB Eiriksdottir, G Garcia, ME Launer, LJ Nalls, MA Clark, JM Mitchell, BD Shuldiner, AR Butler, JL Hoffmann, U Massaro, JM O'Donnell, CJ Sahani, DV Carri, J Feitosa, MF Gudnason, V Fox, CS Smith, AV Kao, WHL Hirschhorn, JN Borecki, IB AF Speliotes, Elizabeth K. Yerges-Armstrong, Laura M. Wu, Jun Hernaez, Ruben Kim, Lauren J. Palmer, Cameron Harris, Tamara B. Eiriksdottir, Gudny Garcia, Melissa E. Launer, Lenore J. Nalls, Michael A. Clark, Jeanne M. Mitchell, Braxton D. Shuldiner, Alan R. Butler, Johannah L. Hoffmann, Udo Massaro, Joseph M. O'Donnell, Christopher J. Sahani, Dushyant V. Carri, Jeffrey Feitosa, Mary F. Gudnason, Vilmundur Fox, Caroline S. Smith, Albert V. Kao, Wen Hong L. Hirschhorn, Joel N. Borecki, Ingrid B. TI GENOME-WIDE ASSOCIATION ANALYSIS IDENTIFIES VARIANTS ASSOCIATED WITH NONALCOHOLIC FATTY LIVER DISEASE THAT HAVE DISTINCT EFFECTS ON SERUM LIPIDS SO HEPATOLOGY LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 29-NOV 02, 2010 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Speliotes, Elizabeth K.; Butler, Johannah L.] Broad Inst, Cambridge, MA USA. [Yerges-Armstrong, Laura M.; Mitchell, Braxton D.; Shuldiner, Alan R.] Univ Maryland, Sch Med, Dept Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA. [Wu, Jun; Feitosa, Mary F.; Borecki, Ingrid B.] Washington Univ, Div Stat Genom, St Louis, MO USA. [Hernaez, Ruben; Kao, Wen Hong L.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Hernaez, Ruben; Clark, Jeanne M.] Johns Hopkins Univ Hosp, Div Gen Internal Med, Baltimore, MD 21287 USA. [Kim, Lauren J.; Harris, Tamara B.; Garcia, Melissa E.; Launer, Lenore J.] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, NIH, Bethesda, MD 20892 USA. [Palmer, Cameron; Butler, Johannah L.; Hirschhorn, Joel N.] Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. [Palmer, Cameron; Butler, Johannah L.; Hirschhorn, Joel N.] Childrens Hosp, Div Genet, Boston, MA 02115 USA. [Palmer, Cameron; Butler, Johannah L.; Hirschhorn, Joel N.] Childrens Hosp, Program Genom, Boston, MA 02115 USA. [Eiriksdottir, Gudny; Gudnason, Vilmundur; Smith, Albert V.] Iceland Heart Assoc, IS-201 Kopavogur, Iceland. [Nalls, Michael A.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Clark, Jeanne M.; Kao, Wen Hong L.] Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA. [Shuldiner, Alan R.] Vet Adm Med Ctr, GRECC, Baltimore, MD 21218 USA. [Hoffmann, Udo; Sahani, Dushyant V.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Massaro, Joseph M.; O'Donnell, Christopher J.; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Massaro, Joseph M.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [O'Donnell, Christopher J.; Fox, Caroline S.] NHLBI, Div Intramural Res, Bethesda, MD 20892 USA. [Carri, Jeffrey] Wake Forest Univ, Sch Med, Dept Radiol Sci, Winston Salem, NC 27109 USA. [Carri, Jeffrey] Wake Forest Univ, Sch Med, Dept Internal Med Cardiol, Winston Salem, NC 27109 USA. [Carri, Jeffrey] Wake Forest Univ, Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27109 USA. [Gudnason, Vilmundur] Univ Iceland, IS-101 Reykjavik, Iceland. [Hirschhorn, Joel N.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. RI Hernaez, Ruben/C-4039-2014; Gudnason, Vilmundur/K-6885-2015; Feitosa, Mary/K-8044-2012 OI Hernaez, Ruben/0000-0002-1518-4020; Gudnason, Vilmundur/0000-0001-5696-0084; Feitosa, Mary/0000-0002-0933-2410 NR 0 TC 1 Z9 1 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2010 VL 52 IS 4 SU S MA 254 BP 450A EP 450A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 740EY UT WOS:000288775600260 ER PT J AU Korrapati, M Ryan, P Chakraborty, M Agrawal, N Pohl, L AF Korrapati, Midhun Ryan, Pauline Chakraborty, Mala Agrawal, Nidhi Pohl, Lance TI ROLE OF INTERLEUKIN-4 AND AUTOPHAGY IN A MOUSE MODEL OF HALOTHANE-INDUCED LIVER INJURY SO HEPATOLOGY LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 29-NOV 02, 2010 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Korrapati, Midhun; Ryan, Pauline; Chakraborty, Mala; Agrawal, Nidhi; Pohl, Lance] NHLBI, Mol & Cellular Toxicol Sect, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2010 VL 52 IS 4 SU S MA 268 BP 456A EP 456A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 740EY UT WOS:000288775600274 ER PT J AU Mi, LJ Karsdon, J Huang, WM Zhang, JH Manheimer, F Tran, TT Brown, RS Ghany, MG AF Mi, Li-Jun Karsdon, Jeffrey Huang, William M. Zhang, Jinghua Manheimer, Forrest Tran, Tram T. Brown, Robert S. Ghany, Marc G. TI OUTCOMES OF EIGHT CHINESE-AMERICANS PREGNANT PATIENTS WITH CHRONIC HEPATITIS B (CHB) TREATED WITH TENOFOVIR DF (TDF) DURING PREGNANCY SO HEPATOLOGY LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 29-NOV 02, 2010 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Mi, Li-Jun; Karsdon, Jeffrey; Huang, William M.; Zhang, Jinghua; Manheimer, Forrest] New York Downtown Hosp, New York, NY USA. [Tran, Tram T.] Cedars Sinai Med Ctr, Liver Dis & Transplant Ctr, Los Angeles, CA 90048 USA. [Brown, Robert S.] New York Presbyterian Med Ctr, Div Abdominal Organ Transplantat, New York, NY USA. [Ghany, Marc G.] NIH, Liver Dis Branch, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2010 VL 52 IS 4 SU S MA 372 BP 505A EP 505A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 740EY UT WOS:000288775600377 ER PT J AU Everson, GT Hoefs, JC Niemann, CU Olthoff, KM Dupuis, R Milne, N Herman, A Lauriski, S Gillespie, BW Lok, AS Baisden, K Everhart, JE AF Everson, Gregory T. Hoefs, John C. Niemann, Claus U. Olthoff, Kim M. Dupuis, Robert Milne, Norah Herman, Andrea Lauriski, Shannon Gillespie, Brenda W. Lok, Anna S. Baisden, Katherine Everhart, James E. TI FUNCTIONAL ELEMENTS ASSOCIATED WITH HEPATIC REGENERATION IN LIVING DONORS AFTER RIGHT LOBECTOMY - A SUB-STUDY OF THE ADULT TO ADULT LIVING DONOR LIVER TRANSPLANTATION COHORT (A2ALL) STUDY SO HEPATOLOGY LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 29-NOV 02, 2010 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Everson, Gregory T.; Herman, Andrea; Lauriski, Shannon] Univ Colorado, Dept Med, Aurora, CO USA. [Hoefs, John C.] Univ Calif Irvine, Dept Med, Orange, CA 92668 USA. [Niemann, Claus U.] Univ Calif San Francisco, Dept Anesthesia & Perioperat Care, San Francisco, CA 94143 USA. [Niemann, Claus U.] Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA. [Olthoff, Kim M.] Univ Penn, Dept Surg, Philadelphia, PA 19104 USA. [Dupuis, Robert] Univ N Carolina, Sch Pharm, Chapel Hill, NC USA. [Milne, Norah] Univ Calif Irvine, Dept Radiol, Orange, CA 92668 USA. [Gillespie, Brenda W.] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. [Lok, Anna S.] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. [Baisden, Katherine] Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA. [Everhart, James E.] NIDDK, Div Digest Dis & Nutr, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2010 VL 52 IS 4 SU S MA 500 BP 569A EP 569A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 740EY UT WOS:000288775600505 ER PT J AU Woo, HG Coulouarn, C Thorgeirsson, SS AF Woo, Hyun Goo Coulouarn, Cedric Thorgeirsson, Snorri S. TI IDENTIFICATION OF REGULATORY MICRORNAS FOR HEPATOCELLULAR CARCINOMA PROGRESSION SO HEPATOLOGY LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 29-NOV 02, 2010 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Woo, Hyun Goo] Ajou Univ Sch Med, Dept Physiol, Suwon, South Korea. [Woo, Hyun Goo; Coulouarn, Cedric; Thorgeirsson, Snorri S.] NCI, Expt Carcinogenesis Lab, Bethesda, MD 20892 USA. RI Coulouarn, Cedric/E-5472-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2010 VL 52 IS 4 SU S MA 529 BP 580A EP 580A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 740EY UT WOS:000288775600531 ER PT J AU Renz, M Lippincott-Schwartz, J Arias, IM AF Renz, Malte Lippincott-Schwartz, Jennifer Arias, Irwin M. TI ASIALOGLYCOPROTEIN RECEPTOR OLIGOMERIZATION, LIGAND BINDING AND FUNCTION SO HEPATOLOGY LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 29-NOV 02, 2010 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Renz, Malte; Lippincott-Schwartz, Jennifer] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, Sect Organelle Biol, NIH, Bethesda, MD USA. [Renz, Malte; Arias, Irwin M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, Unit Cellular Polar, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2010 VL 52 IS 4 SU S MA 545 BP 586A EP 587A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 740EY UT WOS:000288775600546 ER PT J AU Fu, D Wakabayashi, Y Lippincott-Schwartz, J Arias, IM AF Fu, Dong Wakabayashi, Yoshiyuki Lippincott-Schwartz, Jennifer Arias, Irwin M. TI NEW FUNCTION OF BILE ACID - REGULATION OF POLARITY AND CELLULAR ENERGY SO HEPATOLOGY LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 29-NOV 02, 2010 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Fu, Dong; Wakabayashi, Yoshiyuki; Lippincott-Schwartz, Jennifer; Arias, Irwin M.] NICHD, NIH, Bethesda, MD USA. RI Fu, Dong /J-1426-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2010 VL 52 IS 4 SU S MA 561 BP 593A EP 593A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 740EY UT WOS:000288775600561 ER PT J AU Katsounas, A Trippler, M Bein, S Lempicki, RA Gerken, G Schlaak, JF AF Katsounas, Antonios Trippler, Martin Bein, Sabine Lempicki, Richard A. Gerken, Guido Schlaak, Joerg F. TI HEAT SHOCK 22KDA PROTEIN 8 (HSPB8) INDUCED SYSTEMIC TOLL-LIKE-RECEPTOR (TLR) 4-DEPENDENT IMMUNE ACTIVATION IS ASSOCIATED WITH SEVERE HEPATIC FIBROSIS IN CHRONIC HEPATITIS C VIRUS INFECTION (CHCV) SO HEPATOLOGY LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 29-NOV 02, 2010 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Katsounas, Antonios; Lempicki, Richard A.] NCI, LIB, SAIC Inc, Frederick, MD 21701 USA. [Katsounas, Antonios; Trippler, Martin; Bein, Sabine; Gerken, Guido; Schlaak, Joerg F.] Univ Hosp Essen, Dept Gastroenterol & Hepatol, Essen, Germany. RI Lempicki, Richard/E-1844-2012 OI Lempicki, Richard/0000-0002-7059-409X NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2010 VL 52 IS 4 SU S MA 609 BP 613A EP 613A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 740EY UT WOS:000288775600608 ER PT J AU Neuschwander-Tetri, BA Sanyal, AJ Chalasani, NP Kowdley, KV McCullough, AJ Diehl, AM Bass, NM Lavine, JE Loomba, R Brunt, EM Kleiner, DE Donithan, M Van Natta, M Tonascia, J Unalp, A Clark, JM Robuck, PR AF Neuschwander-Tetri, Brent A. Sanyal, Arun J. Chalasani, Naga P. Kowdley, Kris V. McCullough, Arthur J. Diehl, Anna Mae Bass, Nathan M. Lavine, Joel E. Loomba, Rohit Brunt, Elizabeth M. Kleiner, David E. Donithan, Michele Van Natta, Mark Tonascia, James Unalp, Aynur Clark, Jeanne M. Robuck, Patricia R. TI CHANGES IN ALT AND VITAMIN E LEVELS AND HISTOLOGICAL RESPONSE IN PATIENTS WITH NASH TREATED WITH VITAMIN E IN THE PIVENS TRIAL SO HEPATOLOGY LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 29-NOV 02, 2010 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Neuschwander-Tetri, Brent A.] St Louis Univ, St Louis, MO 63103 USA. [Sanyal, Arun J.] Virginia Commonwealth Univ, Richmond, VA USA. [Chalasani, Naga P.] Indiana Univ, Indianapolis, IN 46204 USA. [Kowdley, Kris V.] Virginia Mason Inst, Seattle, WA USA. [McCullough, Arthur J.] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Diehl, Anna Mae] Duke Univ, Durham, NC USA. [Bass, Nathan M.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Lavine, Joel E.] Columbia Univ, New York, NY USA. [Loomba, Rohit] Univ Calif San Diego, San Diego, CA 92103 USA. [Brunt, Elizabeth M.] Washington Univ, St Louis, MO USA. [Kleiner, David E.] NCI, Bethesda, MD 20892 USA. [Donithan, Michele; Van Natta, Mark; Tonascia, James; Unalp, Aynur; Clark, Jeanne M.] Johns Hopkins Univ, Baltimore, MD USA. [Robuck, Patricia R.] NIDDKD, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 3 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2010 VL 52 IS 4 SU S MA 626 BP 620A EP 621A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 740EY UT WOS:000288775600625 ER PT J AU Murphy, AA Kottilil, S Yang, J Lempicki, RA Sneller, M AF Murphy, Alison A. Kottilil, Shyam Yang, Jun Lempicki, Richard A. Sneller, Michael TI PATHOGENIC B CELL EXPANSION OBSERVED IN HCV MIXED CRYOGLOBULINEMIC VASCULITIS PATIENTS RESULTS IN ACTIVATION OF MONOCYTES AND INNATE IMMUNE ACTIVATION SO HEPATOLOGY LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 29-NOV 02, 2010 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Murphy, Alison A.; Kottilil, Shyam; Sneller, Michael] NIAID, LIR, NIH, Bethesda, MD 20892 USA. [Yang, Jun; Lempicki, Richard A.] NCI, SAIC Frederick, Frederick, MD 21701 USA. RI Lempicki, Richard/E-1844-2012 OI Lempicki, Richard/0000-0002-7059-409X NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2010 VL 52 IS 4 SU S MA 735 BP 671A EP 671A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 740EY UT WOS:000288775601054 ER PT J AU Li, QS Zhang, YY Hu, ZY Lan, KH Liang, TJ AF Li, Qisheng Zhang, Yong-Yuan Hu, Zongyi Lan, Keng-Hsin Liang, T. Jake TI SYSTEMS BIOLOGY OF HOST DEPENDENCIES IN COMPLETE LIFECYCLE OF HEPATITIS C VIRUS SO HEPATOLOGY LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 29-NOV 02, 2010 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Li, Qisheng; Zhang, Yong-Yuan; Hu, Zongyi; Lan, Keng-Hsin; Liang, T. Jake] NIDDK, Liver Dis Branch, NIH, Bethesda, MD USA. RI Li, Qisheng/K-1909-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2010 VL 52 IS 4 SU S MA 852 BP 731A EP 731A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 740EY UT WOS:000288775601171 ER PT J AU Sugalski, JM Rodriguez, B Moir, S Anthony, DD AF Sugalski, Julia M. Rodriguez, Benigno Moir, Susan Anthony, Donald D. TI PERIPHERAL BLOOD B CELL SUBSET SKEWING IS ASSOCIATED WITH ALTERED CELL CYCLING, INTRINSIC RESISTANCE TO APOPTOSIS AND REFLECTS A STATE OF IMMUNE ACTIVATION IN CHRONIC HCV INFECTION SO HEPATOLOGY LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 29-NOV 02, 2010 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Sugalski, Julia M.; Rodriguez, Benigno; Anthony, Donald D.] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Moir, Susan] NIAID, Immunoregulat Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2010 VL 52 IS 4 SU S MA 860 BP 734A EP 734A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 740EY UT WOS:000288775601179 ER PT J AU Thomas, E Gonzalez, VD Noureddin, M Rotman, Y Liang, TJ AF Thomas, Emmanuel Gonzalez, Veronica D. Noureddin, Mazen Rotman, Yaron Liang, T. Jake TI CHARACTERIZATION OF THE INTERFERON LAMBDA (IL28/29) ANTIVIRAL PATHWAY IN CELL CULTURE, HUMAN AND CHIMPANZEE MODELS OF HCV INFECTION SO HEPATOLOGY LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 29-NOV 02, 2010 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Thomas, Emmanuel; Gonzalez, Veronica D.; Noureddin, Mazen; Rotman, Yaron; Liang, T. Jake] NIDDK, NIH, LDB, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2010 VL 52 IS 4 SU S MA 876 BP 741A EP 742A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 740EY UT WOS:000288775601195 ER PT J AU Trehanpati, N Kottilil, S Murphy, AA Zhang, XZ Sarin, SK AF Trehanpati, Nirupma Kottilil, Shyam Murphy, Alison A. Zhang, Xiaozhen Sarin, Shiv K. TI INCREASED TALL-1/B-CELL ACTIVATING FACTOR (BAFF) EXPRESSION AS A MECHANISM FOR ABERRANT B CELL FUNCTION IN HCV INFECTED PATIENTS SO HEPATOLOGY LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 29-NOV 02, 2010 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Kottilil, Shyam; Murphy, Alison A.; Zhang, Xiaozhen] NIAID, LIR, NIH, Bethesda, MD 20892 USA. [Trehanpati, Nirupma; Sarin, Shiv K.] Inst Livver & Biliary Sci, New Delhi, India. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2010 VL 52 IS 4 SU S MA 894 BP 749A EP 749A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 740EY UT WOS:000288775601213 ER PT J AU Osinusi, A Murphy, AA Masur, H Polis, MA Kottilil, S AF Osinusi, Anu Murphy, Alison A. Masur, Henry Polis, Michael A. Kottilil, Shyam TI TH-17 CYTOKINES PROMOTE INTERFERON RESPONSIVENESS IN HIV/HCV COINFECTED PATIENTS WHO ACHIEVED SUSTAINED VIROLOGIC RESPONSE SO HEPATOLOGY LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 29-NOV 02, 2010 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Osinusi, Anu; Murphy, Alison A.; Polis, Michael A.; Kottilil, Shyam] NIAID, LIR, NIH, Bethesda, MD 20892 USA. [Masur, Henry] NIH, CCMD, CC, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2010 VL 52 IS 4 SU S MA 946 BP 776A EP 777A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 740EY UT WOS:000288775601264 ER PT J AU Derbala, MF Amer, AM Shebl, F John, A Amin, A John, A Sharma, M Alkaabi, SR Al Dweik, NZ Pasic, FI Yaqoob, R Butt, MT Almohanadi, M AF Derbala, Moutaz F. Amer, Aliaa M. Shebl, Fatma John, Anil Amin, Ashraf John, Anjum Sharma, Manik Alkaabi, Saad R. Al Dweik, Nazeeh Z. Pasic, Fuad I. Yaqoob, Rafie Butt, Mohammed T. Almohanadi, Muneera TI HEPATITIS C GENOTYPE 4 WITH NORMAL TRANSAMINASES AND SCHISTOSOMIASIS CO-INFECTION: HISTOLOGICAL CHANGES, RESPONSE RATE, LATE RELAPSE, AND HEMATOLOGICAL ADVERSE EFFECT SO HEPATOLOGY LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 29-NOV 02, 2010 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Derbala, Moutaz F.] Hamad Hosp Weill Cornell Med Coll Qatar, Doha, Qatar. [Amer, Aliaa M.] Hamad Hosp, Hematol Sect, Dept Lab Med & Pathol, Doha, Qatar. [Shebl, Fatma] Natl Canc Inst, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. [John, Anjum] Hamad Hosp, Med Res Ctr, Doha, Qatar. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2010 VL 52 IS 4 SU S MA 960 BP 783A EP 783A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 740EY UT WOS:000288775601278 ER PT J AU Ahlenstiel, G Edlich, B Hogdal, L Rotman, Y Noureddin, M Feld, JJ Titerence, RH Liang, TJ Rehermann, B AF Ahlenstiel, Golo Edlich, Birgit Hogdal, Leah Rotman, Yaron Noureddin, Mazen Feld, Jordan J. Titerence, Rachel H. Liang, T. Jake Rehermann, Barbara TI INTERFERON-ALFA/RIBAVIRIN THERAPY INDUCES RAPID CHANGES IN NATURAL KILLER CELL PHENOTYPE AND FUNCTION IN VIVO SO HEPATOLOGY LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 29-NOV 02, 2010 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Ahlenstiel, Golo; Edlich, Birgit; Hogdal, Leah; Rotman, Yaron; Noureddin, Mazen; Feld, Jordan J.; Titerence, Rachel H.; Liang, T. Jake; Rehermann, Barbara] NIDDK, Liver Dis Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2010 VL 52 IS 4 SU S MA 981 BP 794A EP 794A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 740EY UT WOS:000288775601299 ER PT J AU Gottwein, JM Scheel, TK Jensen, TB Mikkelsen, LS Ghanem, L Bukh, J AF Gottwein, Judith M. Scheel, Troels K. Jensen, Tanja B. Mikkelsen, Lotte S. Ghanem, Lubna Bukh, Jens TI GENOTYPE SPECIFIC STUDIES OF EFFICACY OF LEAD COMPOUND HCV PROTEASE AND NS5A INHIBITORS USING NOVEL CELL CULTURE INFECTIOUS HCV RECOMBINANTS EXPRESSING NS3/NS4A PROTEASE, NS4A, OR NS5A OF GENOTYPES 1-7 SO HEPATOLOGY LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 29-NOV 02, 2010 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Gottwein, Judith M.; Scheel, Troels K.; Jensen, Tanja B.; Mikkelsen, Lotte S.; Ghanem, Lubna; Bukh, Jens] Univ Copenhagen, Hvidovre Hosp, Copenhagen Hepatitis C Program CO HEP, Dept Infect Dis, DK-1168 Copenhagen, Denmark. [Gottwein, Judith M.; Scheel, Troels K.; Jensen, Tanja B.; Mikkelsen, Lotte S.; Ghanem, Lubna; Bukh, Jens] Univ Copenhagen, Hvidovre Hosp, Clin Res Ctr, DK-1168 Copenhagen, Denmark. [Gottwein, Judith M.; Scheel, Troels K.; Jensen, Tanja B.; Mikkelsen, Lotte S.; Ghanem, Lubna; Bukh, Jens] Univ Copenhagen, Hvidovre Hosp, Fac Hlth Sci, Dept Int Hlth Immunol & Microbiol, DK-1168 Copenhagen, Denmark. [Gottwein, Judith M.; Scheel, Troels K.; Jensen, Tanja B.; Mikkelsen, Lotte S.; Ghanem, Lubna; Bukh, Jens] Univ Copenhagen, Hvidovre, Denmark. [Gottwein, Judith M.; Scheel, Troels K.; Jensen, Tanja B.; Mikkelsen, Lotte S.; Ghanem, Lubna; Bukh, Jens] Univ Copenhagen, Copenhagen, Denmark. [Bukh, Jens] NIAID, Infect Dis Lab, Hepatitis Viruses Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2010 VL 52 IS 4 SU S MA 1026 BP 816A EP 816A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 740EY UT WOS:000288775601344 ER PT J AU Kawaguchi, K Faulk, KN Honda, M Kaneko, S Purcell, RH Emerson, SU AF Kawaguchi, Kazunori Faulk, Kristina N. Honda, Masao Kaneko, Shuichi Purcell, Robert H. Emerson, Suzanne U. TI HVR1 QUASISPECIES SELECTION AND NEUTRALIZATION BY ANTI-HVR1 OF HCV IN CELL CULTURE ARE STRONGLY INFLUENCED BY MUTATIONS IN THE E1E2 REGION OUTSIDE OF HVR1 SO HEPATOLOGY LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 29-NOV 02, 2010 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Kawaguchi, Kazunori; Faulk, Kristina N.; Purcell, Robert H.; Emerson, Suzanne U.] NIAID, Mol Hepatitis & Hepatitis Viruses Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Kawaguchi, Kazunori; Honda, Masao; Kaneko, Shuichi] Kanazawa Univ, Kanazawa, Ishikawa, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2010 VL 52 IS 4 SU S MA 1030 BP 818A EP 818A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 740EY UT WOS:000288775601348 ER PT J AU Shebl, FM Maeder, DL Shao, YW Prokunina-Olsson, L Schadt, E O'Brien, TR AF Shebl, Fatma M. Maeder, Dennis L. Shao, Yongwu Prokunina-Olsson, Ludmila Schadt, Eric O'Brien, Thomas R. TI ABSENT HCV INFECTION, IL28B GENOTYPE IS NOT ASSOCIATED WITH INTERFERON STIMULATED GENE EXPRESSION IN LIVER SO HEPATOLOGY LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 29-NOV 02, 2010 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Shebl, Fatma M.; Maeder, Dennis L.; Prokunina-Olsson, Ludmila; O'Brien, Thomas R.] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. [Maeder, Dennis L.] NCI, Core Genotyping Facil, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21701 USA. [Shao, Yongwu] Informat Management Serv Inc, Silver Spring, MD USA. [Schadt, Eric] Pacific Biosci, Menlo Pk, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2010 VL 52 IS 4 SU S MA LB-19 BP 884A EP 884A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 740EY UT WOS:000288775601487 ER PT J AU Koh, C Chernick, M Zhao, XC Eccleston, J Sakiani, S Hoofnagle, JH Heller, T AF Koh, Christopher Chernick, Milica Zhao, Xiongce Eccleston, Jason Sakiani, Sasan Hoofnagle, Jay H. Heller, Theo TI LONG TERM FOLLOW-UP OF ADULT CYSTIC FIBROSIS PATIENTS: NONINVASIVE MARKERS PREDICT A SECOND WAVE OF LIVER DISEASE SO HEPATOLOGY LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 29-NOV 02, 2010 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Koh, Christopher; Eccleston, Jason; Sakiani, Sasan; Hoofnagle, Jay H.; Heller, Theo] NIDDK, Liver Dis Branch, NIH, Baltimore, MD USA. [Chernick, Milica; Zhao, Xiongce] NIDDK, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2010 VL 52 IS 4 SU S MA 1202 BP 905A EP 905A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 740EY UT WOS:000288775601532 ER PT J AU Wang, H Lafdil, F Park, O Yin, S Gao, B Gao, B AF Wang, Hua Lafdil, Fouad Park, Ogyi Yin, Shi Gao, Bin Gao, Bin TI OPPOSING FUNCTIONS OF SIGNAL TRANSDUCER AND ACTIVATOR OF TRANSCRIPTION 3 IN LIVER TUMORIGENESIS SO HEPATOLOGY LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 29-NOV 02, 2010 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Wang, Hua; Lafdil, Fouad; Park, Ogyi; Yin, Shi; Gao, Bin; Gao, Bin] NIAAA, Lab Liver Dis, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2010 VL 52 IS 4 SU S MA 1274 BP 937A EP 938A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 740EY UT WOS:000288775601604 ER PT J AU Becker, D Sfakianakis, I Krupp, M Staib, F Victor, A Blettner, M Maass, T Thorgeirsson, SS Galle, PR Teufel, A AF Becker, Diana Sfakianakis, Ioannis Krupp, Markus Staib, Frank Victor, Anja Blettner, Maria Maass, Thorsten Thorgeirsson, Snorri S. Galle, Peter R. Teufel, Andreas TI GENETIC SIGNATURES SHARED IN EMBRYONIC LIVER DEVELOPMENT AND LIVER CANCER DEFINE PROGNOSTICALLY RELEVANT SUBGROUPS IN HCC SO HEPATOLOGY LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 29-NOV 02, 2010 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Becker, Diana; Sfakianakis, Ioannis; Krupp, Markus; Staib, Frank; Maass, Thorsten; Galle, Peter R.; Teufel, Andreas] Johannes Gutenberg Univ Mainz, Dept Med 1, D-6500 Mainz, Germany. [Thorgeirsson, Snorri S.] NCI, LEC, NIH, Bethesda, MD 20892 USA. [Victor, Anja; Blettner, Maria] Johannes Gutenberg Univ Mainz, IMBEI, Mainz, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2010 VL 52 IS 4 SU S MA 1296 BP 947A EP 947A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 740EY UT WOS:000288775601626 ER PT J AU Kitade, M Factor, VM Marquardt, JU Holczbauer, A Lee, YH Conner, EA Thorgeirsson, SS AF Kitade, Mitsuteru Factor, Valentina M. Marquardt, Jens U. Holczbauer, Agnes Lee, Yun-Han Conner, Elizabeth A. Thorgeirsson, Snorri S. TI THE ROLE OF C-MET AND EGFR SIGNALING IN LIVER PROGENITOR CELL BIOLOGY SO HEPATOLOGY LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 29-NOV 02, 2010 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Kitade, Mitsuteru; Factor, Valentina M.; Marquardt, Jens U.; Holczbauer, Agnes; Lee, Yun-Han; Conner, Elizabeth A.; Thorgeirsson, Snorri S.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2010 VL 52 IS 4 SU S MA 1344 BP 968A EP 968A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 740EY UT WOS:000288775601674 ER PT J AU Kurbanov, F Martin, MP Qi, Y Goedert, JJ Hussain, SK Kirk, GD Hoots, WK Buchbinder, S Thomas, DL Carrington, M Thio, CL AF Kurbanov, Fuat Martin, Maureen P. Qi, Ying Goedert, James J. Hussain, Shehnaz K. Kirk, Gregory D. Hoots, W. K. Buchbinder, Susan Thomas, David L. Carrington, Mary Thio, Chloe L. TI AN IL28B SNP THAT IS ASSOCIATED WITH HCV OUTCOME IS NOT ASSOCIATED WITH HBV OR HIV OUTCOME SO HEPATOLOGY LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 29-NOV 02, 2010 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Kurbanov, Fuat; Kirk, Gregory D.; Thomas, David L.; Thio, Chloe L.] Johns Hopkins Univ, Sch Med, Div Infect Dis, Baltimore, MD 21205 USA. [Martin, Maureen P.; Qi, Ying; Carrington, Mary] NCI, Expt Immunol Lab, SAIC Frederick Inc, Frederick, MD 21701 USA. [Goedert, James J.] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. [Hussain, Shehnaz K.] Univ Calif Los Angeles, Los Angeles, CA USA. [Hoots, W. K.] NHLBI, Div Blood Dis & Resources, Bethesda, MD 20892 USA. [Buchbinder, Susan] Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2010 VL 52 IS 4 SU S MA 1408 BP 997A EP 997A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 740EY UT WOS:000288775602028 ER PT J AU Ki, SH Park, O Zheng, MQ Morales, O Kolls, J Bataller, R Gao, B AF Ki, Sung Hwan Park, Ogyi Zheng, Mingquan Morales, Oriol Kolls, Jay Bataller, Ramon Gao, Bin TI INTERLEUKIN-22 TREATMENT AMELIORATES ALCOHOLIC LIVER INJURY IN A MURINE MODEL OF CHRONIC PLUS BINGE ETHANOL FEEDING: ROLE OF STAT3 SO HEPATOLOGY LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 29-NOV 02, 2010 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Ki, Sung Hwan; Park, Ogyi; Gao, Bin] NIAAA, NIH, Bethesda, MD USA. [Zheng, Mingquan; Kolls, Jay] Louisiana State Univ, New Orleans, LA USA. [Morales, Oriol; Bataller, Ramon] Hosp Clin Barcelona, Liver Unit, Barcelona, Spain. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2010 VL 52 IS 4 SU S MA 1665 BP 1115A EP 1115A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 740EY UT WOS:000288775602285 ER PT J AU Katsounas, A McLaughlin, M Kleiner, DE Heller, T Hu, XJ Zheng, X Yang, J Huang, DW Lempicki, RA Kovacs, JA Morse, C AF Katsounas, Antonios McLaughlin, Mary Kleiner, David E. Heller, Theo Hu, Xiaojun Zheng, Xin Yang, Jun Huang, Da Wei Lempicki, Richard A. Kovacs, Joseph A. Morse, Caryn TI HEPATIC GENE EXPRESSION PROFILES IN HIV-PATIENTS WITHOUT HEPATITIS B OR C CO-INFECTION EXPERIENCING SERUM TRANSAMINASE ELEVATIONS DURING ANTIRETROVIRAL THERAPY (ART) SO HEPATOLOGY LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 29-NOV 02, 2010 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Katsounas, Antonios; Hu, Xiaojun; Zheng, Xin; Yang, Jun; Huang, Da Wei; Lempicki, Richard A.] SAIC Inc, LIB, NCI Frederick, Frederick, MD USA. [McLaughlin, Mary; Morse, Caryn] NIAID, LIR, NIH, Bethesda, MD 20892 USA. [Kleiner, David E.] NCI, Pathol Lab, Bethesda, MD 20892 USA. [Heller, Theo] NIDDK, LDB, NIH, Bethesda, MD USA. [Kovacs, Joseph A.] NIH, Ctr Clin, Bethesda, MD 20892 USA. RI Lempicki, Richard/E-1844-2012 OI Lempicki, Richard/0000-0002-7059-409X NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2010 VL 52 IS 4 SU S MA 1693 BP 1127A EP 1127A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 740EY UT WOS:000288775602313 ER PT J AU Wang, C Zhang, XZ Osinusi, A Masur, H Fishbein, D Kottilil, S AF Wang, Crystal Zhang, Xiaozhen Osinusi, Anu Masur, Henry Fishbein, Dawn Kottilil, Shyam TI AUGMENTATION OF INTERFERON SIGNALING PATHWAY BY NITAZOXANIDE: A NOVEL THERAPEUTIC STRATEGY FOR RELAPSERS TO PEG-INTERFERON AND RIBAVIRIN THERAPY SO HEPATOLOGY LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 29-NOV 02, 2010 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Wang, Crystal; Zhang, Xiaozhen; Osinusi, Anu; Kottilil, Shyam] NIAID, LIR, NIH, Bethesda, MD 20892 USA. [Masur, Henry] NIH, CCMD, CC, Bethesda, MD 20892 USA. [Fishbein, Dawn] NIH, SAIC Frederick Inc, CMRP, CCMD, Frederick, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2010 VL 52 IS 4 SU S MA 1878 BP 1213A EP 1213A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 740EY UT WOS:000288775602496 ER PT J AU Thomas, E Li, QS Liang, TJ AF Thomas, Emmanuel Li, Qisheng Liang, T. Jake TI TOWARDS THE IDENTIFICATION OF GENES INVOLVED IN THE ANTIVIRAL ACTIVITY OF RIBAVIRIN AGAINST HCV INFECTION SO HEPATOLOGY LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 29-NOV 02, 2010 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Thomas, Emmanuel; Li, Qisheng; Liang, T. Jake] NIDDK, NIH, LDB, Bethesda, MD USA. RI Li, Qisheng/K-1909-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2010 VL 52 IS 4 SU S MA 1882 BP 1215A EP 1215A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 740EY UT WOS:000288775602500 ER PT J AU Dutta, A Guralnik, J Wallace, R Melzer, D AF Dutta, A. Guralnik, J. Wallace, R. Melzer, D. TI EARLY LIFE PREDICTORS OF EXCEPTIONAL SURVIVAL IN THE IOWA EPESE-STUDY SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Dutta, A.; Melzer, D.] Univ Exeter, Exeter, Devon, England. [Guralnik, J.] NIA, Bethesda, MD USA. [Wallace, R.] Univ Iowa, Iowa City, IA USA. OI Dutta, Ambarish/0000-0002-4019-7472 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 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 19 EP 19 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006701091 ER PT J AU Wallace, RB Dutta, A Guralnik, J Melzer, D AF Wallace, R. B. Dutta, A. Guralnik, J. Melzer, D. TI IOWA 2: BLOOD BIOCHEMISTRY AND THE PREDICTION OF SURVIVAL IN THE IOWA-EPESE SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Dutta, A.; Melzer, D.] Univ Exeter, Exeter, Devon, England. [Guralnik, J.] NIA, Bethesda, MD 20892 USA. [Wallace, R. B.] Univ Iowa, Iowa City, IA USA. OI Dutta, Ambarish/0000-0002-4019-7472 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 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 20 EP 20 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006701093 ER PT J AU Ward, RE Boudreau, R Rosano, C Newman, MA Goodpaster, B Harris, T Newman, AB Strotmeyer, ES AF Ward, R. E. Boudreau, R. Rosano, C. Newman, M. A. Goodpaster, B. Harris, T. Newman, A. B. Strotmeyer, E. S. TI LEG POWER AND FUNCTIONAL MOBILITY IN THE OLDEST OLD: THE HEALTH, AGING AND BODY COMPOSITION STUDY SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Ward, R. E.; Boudreau, R.; Rosano, C.; Newman, M. A.; Goodpaster, B.; Newman, A. B.; Strotmeyer, E. S.] Univ Pittsburgh, Pittsburgh, PA USA. [Harris, T.] NIA, Bethesda, MD 20892 USA. RI Strotmeyer, Elsa/F-3015-2014 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 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 41 EP 41 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006701196 ER PT J AU Watson, NL Harris, TB Kritchevsky, SB Satterfield, S Hue, TF Newman, AB AF Watson, N. L. Harris, T. B. Kritchevsky, S. B. Satterfield, S. Hue, T. F. Newman, A. B. TI LONGITUDINAL LOSS OF LEAN MASS AND MORTALITY RISK IN OLDER ADULTS SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Watson, N. L.; Newman, A. B.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Harris, T. B.] NIA, Intramural Res Program, Bethesda, MD 20892 USA. [Kritchevsky, S. B.] Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA. [Satterfield, S.] Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA. [Hue, T. F.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Newman, A. B.] Univ Pittsburgh, Dept Med, Pittsburgh, PA 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 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 41 EP 41 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006701194 ER PT J AU Manini, T Patel, K Bauer, DC Ziv, E Schoeller, D Mackey, D Newman, AB Harris, TB AF Manini, T. Patel, K. Bauer, D. C. Ziv, E. Schoeller, D. Mackey, D. Newman, A. B. Harris, T. B. TI EUROPEAN ANCESTRY AND RESTING METABOLIC RATE IN OLDER PERSONS SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Manini, T.] Univ Florida, Gainesville, FL USA. [Schoeller, D.] Univ Wisconsin, Madison, WI USA. [Patel, K.; Harris, T. B.] NIA, Bethesda, MD 20892 USA. [Newman, A. B.] Univ Pittsburgh, Pittsburgh, PA USA. [Bauer, D. C.; Ziv, E.; Mackey, D.] Univ San Francisco, San Francisco, CA 94117 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 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 44 EP 44 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006701207 ER PT J AU Barr, R AF Barr, R. TI NIA SYMPOSIUM: TRAINING OPPORTUNITIES IN AGING RESEARCH - A RUN THROUGH THE NIA AND NIH MAZE SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Barr, R.] NIA, 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 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 59 EP 59 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006701280 ER PT J AU Harden, J AF Harden, J. TI NIA SYMPOSIUM: INTERACTIVE ROUNDTABLE DISCUSSIONS ON RESEARCH AND CARE ACROSS THE AGE CONTINUUM SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Harden, J.] NIA, 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 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 59 EP 59 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006701279 ER PT J AU Chang, M Saczynski, J Sigurdsson, S Gudnason, V Harris, TB Launer, LJ Jonsson, PV AF Chang, M. Saczynski, J. Sigurdsson, S. Gudnason, V. Harris, T. B. Launer, L. J. Jonsson, P. V. TI THE ASSOCIATION BETWEEN MIDLIFE BODY MASS INDEX AND BRAIN VOLUME IN LATE LIFE: AGE GENE/ENVIRONMENT SUSCEPTIBILITY - REYKJAVIK STUDY SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Chang, M.; Jonsson, P. V.] Landspitali Univ Hosp, Reykjavik, Iceland. [Saczynski, J.] Univ Massachusetts, Sch Med, Worcester, MA USA. [Sigurdsson, S.; Gudnason, V.] Iceland Heart Assoc, Kopavogur, Iceland. [Gudnason, V.; Jonsson, P. V.] Univ Iceland, Reykjavik, Iceland. [Harris, T. B.; Launer, L. J.] NIA, Bethesda, MD 20892 USA. RI Gudnason, Vilmundur/K-6885-2015 OI Gudnason, Vilmundur/0000-0001-5696-0084 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 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 82 EP 82 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006701394 ER PT J AU Harris, T AF Harris, T. TI RESILIENCE AND RESERVE IN OLD AGE: FIXED OR FLUID? SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Harris, T.] NIA, 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 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 89 EP 89 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006701422 ER PT J AU Rooks, RN Harris, TB AF Rooks, R. N. Harris, T. B. TI WHO WORKS AMONG OLDER BLACK AND WHITE, WELL-FUNCTIONING ADULTS IN THE HEALTH ABC STUDY? SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Rooks, R. N.] Univ Colorado, Denver, CO 80202 USA. [Harris, T. B.] Natl Inst Aging, Bethesda, MD 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 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 122 EP 122 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006701587 ER PT J AU Ko, S Ling, SM Schreiber, C Nesbitt, M Ferrucci, L AF Ko, S. Ling, S. M. Schreiber, C. Nesbitt, M. Ferrucci, L. TI IMPACT OF KNEE OA ON GAIT AND MECHANICAL WORK EXPENDITURE IN OLDER ADULTS: THE BLSA GAIT LAB SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Ko, S.; Ling, S. M.; Schreiber, C.; Nesbitt, M.; Ferrucci, L.] NIA, NIH, Baltimore, MD 21224 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 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 125 EP 125 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006701600 ER PT J AU Schrack, J Simonsick, EM Chaves, PH Ferrucci, L AF Schrack, J. Simonsick, E. M. Chaves, P. H. Ferrucci, L. TI WALKING SPEED AND ENERGETIC EFFICIENCY IN OLDER ADULTS SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Schrack, J.; Chaves, P. H.] Johns Hopkins Sch Publ Hlth, Baltimore, MD USA. [Schrack, J.; Simonsick, E. M.; Ferrucci, L.] NIA, NIH, Baltimore, MD 21224 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 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 125 EP 125 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006701599 ER PT J AU Simonsick, EM Schrack, J Ferrucci, L AF Simonsick, E. M. Schrack, J. Ferrucci, L. TI THYROID FUNCTION AND WALKING-RELATED PERFORMANCE AND ENERGETICS IN LATE LIFE SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Simonsick, E. M.; Schrack, J.; Ferrucci, L.] NIA, Baltimore, MD 21224 USA. [Simonsick, E. M.; Schrack, J.] Johns Hopkins Med Inst, Baltimore, MD 21205 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 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 125 EP 125 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006701601 ER PT J AU Strotmeyer, ES Boudreau, R Zivkovic, S Vinik, AI Schwartz, AV Satterfield, S Harris, TB Newman, AB AF Strotmeyer, E. S. Boudreau, R. Zivkovic, S. Vinik, A. I. Schwartz, A. V. Satterfield, S. Harris, T. B. Newman, A. B. TI DO TRADITIONAL OR NON-TRADITIONAL RISK FACTORS FOR NEUROPATHY PREDICT NERVE FUNCTION DECLINE IN OLDER ADULTS? SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Strotmeyer, E. S.; Boudreau, R.; Zivkovic, S.; Newman, A. B.] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA. [Vinik, A. I.] Eastern Virginia Med Sch, Norfolk, VA 23501 USA. [Schwartz, A. V.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Satterfield, S.] Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA. [Harris, T. B.] NIA, Bethesda, MD 20892 USA. [Newman, A. B.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. RI Strotmeyer, Elsa/F-3015-2014 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 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 129 EP 129 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006701617 ER PT J AU Deshpande, N Metter, E Ferrucci, L AF Deshpande, N. Metter, E. Ferrucci, L. TI SENSORY-MOTOR AND PSYCHOSOCIAL DETERMINANTS OF ADAPTIVE LOCOMOTOR PERFORMANCE: THE INCHIANTI STUDY SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Deshpande, N.] Queens Univ, Kingston, ON, Canada. [Metter, E.; Ferrucci, L.] NIA, NIH, Baltimore, MD 21224 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 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 130 EP 131 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006701624 ER PT J AU Evans, J AF Evans, J. TI OPPORTUNITIES AND NEW DIRECTIONS IN TRANSLATIONAL NEUROSCIENCE AND BEHAVIORAL SCIENCE RESEARCH IN GERIATRIC MENTAL HEALTH SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Evans, J.] NIMH, 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 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 156 EP 157 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006701752 ER PT J AU Niederehe, G AF Niederehe, G. TI THE NIH CONTEXT: TRENDS, RECENT DEVELOPMENTS, AND THE GRANTS PROCESS SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Niederehe, G.] NIMH, Geriatr Res Branch, 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 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 156 EP 156 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006701751 ER PT J AU Niederehe, G Evans, J AF Niederehe, G. Evans, J. TI OPPORTUNITIES AND NEW DIRECTIONS IN GERIATRIC MENTAL HEALTH INTERVENTION RESEARCH SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Niederehe, G.; Evans, J.] NIMH, Geriatr Res Branch, 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 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 157 EP 157 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006701753 ER PT J AU Crasto, C Semba, R Sun, K Dalal, MS Bandinelli, S Guralnik, J Ferrucci, L AF Crasto, C. Semba, R. Sun, K. Dalal, M. S. Bandinelli, S. Guralnik, J. Ferrucci, L. TI RELATIONSHIP OF INFLAMMATION AND ANTIOXIDANTS WITH ENDOGENOUS SECRETORY RECEPTOR FOR ADVANCED GLYCATION END PRODUCTS IN OLDER COMMUNITY-DWELLING ADULTS SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Crasto, C.; Semba, R.; Sun, K.; Dalal, M. S.] Johns Hopkins, Baltimore, MD USA. [Bandinelli, S.] Azienda Sanitaria Firenze, Florence, Italy. [Guralnik, J.] NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA. [Ferrucci, L.] NIA, Longitudinal Studies Sect, Clin Res Branch, NIH, Baltimore, MD 21224 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 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 182 EP 182 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006701874 ER PT J AU Dalal, MS Semba, R Sun, K Bandinelli, S Varadhan, R Walston, J Guralnik, J Ferrucci, L AF Dalal, M. S. Semba, R. Sun, K. Bandinelli, S. Varadhan, R. Walston, J. Guralnik, J. Ferrucci, L. TI ENDOGENOUS SECRETORY RECEPTOR FOR ADVANCED GLYCATION END PRODUCTS AND CHRONIC KIDNEY DISEASE SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Dalal, M. S.; Semba, R.; Sun, K.; Varadhan, R.; Walston, J.] Johns Hopkins Med Inst, Baltimore, MD 21205 USA. [Guralnik, J.] NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA. [Ferrucci, L.] NIA, Longitudinal Studies Sect, Clin Res Branch, NIH, Baltimore, MD 21224 USA. [Bandinelli, S.] Azienda Sanitaria Firenze, Florence, Italy. 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 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 182 EP 182 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006701873 ER PT J AU Cauley, JA Houston, DK Barbour, K Boudreau, R Bauer, DC Tylavsky, FA Harrris, TB Kritchevsky, SB AF Cauley, J. A. Houston, D. K. Barbour, K. Boudreau, R. Bauer, D. C. Tylavsky, F. A. Harrris, T. B. Kritchevsky, S. B. TI VITAMIN D STATUS AND THE RISK OF FRACTURE SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Cauley, J. A.; Barbour, K.; Boudreau, R.] Univ Pittsburgh, Pgh, PA USA. [Houston, D. K.; Kritchevsky, S. B.] Wake Forest Univ, Winston Salem, NC 27109 USA. [Bauer, D. C.] Univ Tennessee, Memphis, TN USA. [Tylavsky, F. A.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Harrris, T. B.] NIA, Bethesda, WA 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 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 218 EP 218 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006702164 ER PT J AU Houston, DK Neiberg, R Tooze, J Hausman, DB Cauley, JA Bauer, DC Harris, T Kritchevsky, SB AF Houston, D. K. Neiberg, R. Tooze, J. Hausman, D. B. Cauley, J. A. Bauer, D. C. Harris, T. Kritchevsky, S. B. TI VITAMIN D STATUS AND INCIDENT MOBILITY LIMITATION IN COMMUNITY-DWELLING OLDER ADULTS SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Houston, D. K.; Neiberg, R.; Tooze, J.; Kritchevsky, S. B.] Wake Forest Univ, Sticht Ctr Aging, Sch Med, Winston Salem, NC 27109 USA. [Hausman, D. B.] Univ Georgia, Athens, GA 30602 USA. [Cauley, J. A.] Univ Pittsburgh, Pittsburgh, PA USA. [Bauer, D. C.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Harris, T.] NIA, 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 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 218 EP 218 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006702163 ER PT J AU Kritchevsky, SB Houston, DK Neiberg, R Tooze, J Hausman, DB Cauley, JA Bauer, DC Harris, T AF Kritchevsky, S. B. Houston, D. K. Neiberg, R. Tooze, J. Hausman, D. B. Cauley, J. A. Bauer, D. C. Harris, T. TI SERUM 25-HYDROXYVITAMIN D, PARATHYROID HORMONE AND MORTALITY IN COMMUNITY-DWELLING OLDER ADULTS SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Kritchevsky, S. B.; Houston, D. K.; Neiberg, R.; Tooze, J.] Wake Forest Univ, Sch Med, Sticht Ctr Aging, Winston Salem, NC 27109 USA. [Hausman, D. B.] Univ Georgia, Athens, GA 30602 USA. [Cauley, J. A.] Univ Pittsburgh, Pittsburgh, PA USA. [Bauer, D. C.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Harris, T.] NIA, 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 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 218 EP 218 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006702165 ER PT J AU Harris, TB Newman, AB Goodpaster, B Kritchevsky, SB Satterfield, S Cummings, SR Visser, M AF Harris, T. B. Newman, A. B. Goodpaster, B. Kritchevsky, S. B. Satterfield, S. Cummings, S. R. Visser, M. TI MAKING SENSE OF BODY MASS INDEX AND BODY COMPOSITION RISK IN OLD AGE: THE HEALTH AGING, AND BODY COMPOSITION STUDY SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Harris, T. B.] NIA, Lab Epidemiol Demog & Biometry, IRP, Bethesda, MD 20892 USA. [Newman, A. B.; Goodpaster, B.] Univ Pittsburgh, Pittsburgh, PA USA. [Kritchevsky, S. B.] Wake Forest Univ, Winston Salem, NC 27109 USA. [Satterfield, S.] U Tennessee Memphis, Memphis, TN USA. [Cummings, S. R.] San Francisco Pacific Med Ctr, San Francisco, CA USA. [Visser, M.] Vjre Univ, Amsterdam, Netherlands. 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 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 246 EP 246 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006702301 ER PT J AU Kim, L Koster, A Eiriksdottir, G Sigurdsson, S Chaves, PH Launer, LJ Gudnason, V Harris, T AF Kim, L. Koster, A. Eiriksdottir, G. Sigurdsson, S. Chaves, P. H. Launer, L. J. Gudnason, V. Harris, T. TI JOINT ASSOCIATION OF VISCERAL AND THIGH SUBCUTANEOUS FAT WITH THE METABOLIC SYNDROME: THE AGES-REYKJAVIK STUDY SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Kim, L.; Koster, A.; Launer, L. J.; Harris, T.] NIA, NIH, Bethesda, MD 20892 USA. [Eiriksdottir, G.; Sigurdsson, S.; Gudnason, V.] Iceland Heart Assoc, Kopavogur, Iceland. [Kim, L.; Chaves, P. H.] Johns Hopkins Univ, Baltimore, MD USA. [Gudnason, V.] Univ Iceland, Kopavogur, Iceland. RI Gudnason, Vilmundur/K-6885-2015 OI Gudnason, Vilmundur/0000-0001-5696-0084 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 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 246 EP 246 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006702299 ER PT J AU Steholm, S Sallinen, J Koster, A Rantanen, T Sainio, P Heliovaara, M Koskinen, S AF Steholm, S. Sallinen, J. Koster, A. Rantanen, T. Sainio, P. Heliovaara, M. Koskinen, S. TI ASSOCIATION BETWEEN WEIGHT HISTORY AND MUSCLE STRENGTH IN OLDER ADULTS SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Steholm, S.; Sainio, P.; Heliovaara, M.; Koskinen, S.] Natl Inst Hlth & Welf, Dept Hlth Funct Capac & Welf, Turku, Finland. [Sallinen, J.; Rantanen, T.] Univ Jyvaskyla, Gerontol Res Ctr, Jyvaskyla, Finland. [Koster, A.] NIA, Lab Epidemiol Demog & Biometry, 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 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 246 EP 246 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006702298 ER PT J AU Leveille, SG Kiely, D Jones, R Shmerling, RH Guralnik, J Bean, JF AF Leveille, S. G. Kiely, D. Jones, R. Shmerling, R. H. Guralnik, J. Bean, J. F. TI CHRONIC MUSCULOSKELETAL PAIN CONTRIBUTES TO ONSET OR WORSENING OF DISABILITY IN AN OLDER POPULATION SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Leveille, S. G.] Univ Massachusetts, Boston, MA 02125 USA. [Leveille, S. G.; Jones, R.; Shmerling, R. H.; Bean, J. F.] Harvard Univ, Sch Med, Boston, MA USA. [Kiely, D.; Jones, R.] Hebrew SeniorLife, Boston, MA USA. [Shmerling, R. H.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Guralnik, J.] NIA, Bethesda, MD 20892 USA. [Bean, J. F.] Spaulding Cambridge Outpatient Ctr, Cambridge, MA USA. RI Bean, Jonathan/F-5798-2017 OI Bean, Jonathan/0000-0001-8385-8210 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 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 247 EP 247 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006702304 ER PT J AU Rosano, C Aizenstein, H Fiocco, AJ Newman, AB Du, Y Venkatraman, V Harris, T Yaffe, K AF Rosano, C. Aizenstein, H. Fiocco, A. J. Newman, A. B. Du, Y. Venkatraman, V. Harris, T. Yaffe, K. TI OVERT AND COVERT BRAIN IMAGING CHARACTERISTICS OF ADULTS WHO MAINTAIN COGNITIVE FUNCTION VERY LATE IN LIFE SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Rosano, C.; Aizenstein, H.; Newman, A. B.; Du, Y.; Venkatraman, V.] Univ Pittsburgh, Pittsburgh, PA USA. [Fiocco, A. J.; Yaffe, K.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Harris, T.] 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 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 247 EP 247 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006702303 ER PT J AU Bernard, M Liggins, C Niederehe, G Hafner-Eaton, C AF Bernard, M. Liggins, C. Niederehe, G. Hafner-Eaton, C. TI INSTITUTE OF MEDICINE'S (IOM) "RETOOLING FOR AN AGING AMERICA" - NATIONAL INSTITUTES OF HEALTH (NIH)'S INVESTMENT IN DEVELOPING INNOVATIVE MODELS OF CARE (MOCS) SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Bernard, M.; Liggins, C.] NIA, Bethesda, MD 20892 USA. [Niederehe, G.] NIMH, Bethesda, MD 20892 USA. [Hafner-Eaton, C.] NINR, 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 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 251 EP 251 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006702322 ER PT J AU Watson, NL Rosano, C Hardy, SE Boudreau, R Simonsick, EM Satterfield, S Ayonayon, HN Newman, AB AF Watson, N. L. Rosano, C. Hardy, S. E. Boudreau, R. Simonsick, E. M. Satterfield, S. Ayonayon, H. N. Newman, A. B. TI RATES OF DECLINE IN COGNITIVE AND PHYSICAL PERFORMANCE PREDICT MORTALITY IN OLDER ADULTS SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Watson, N. L.; Rosano, C.; Boudreau, R.; Newman, A. B.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Hardy, S. E.; Newman, A. B.] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. [Simonsick, E. M.] NIA, Intramural Res Program, Baltimore, MD 21224 USA. [Satterfield, S.] Univ Tennessee Hlth Sci Ctr, Memphis, TN USA. [Ayonayon, H. N.] Univ Calif San Francisco, San Francisco, CA 94143 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 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 254 EP 254 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006702334 ER PT J AU Sanders, J Iannaccone, A Boudreau, R Conley, Y Hsueh, W Cawthon, RM Harris, T Newman, AB AF Sanders, J. Iannaccone, A. Boudreau, R. Conley, Y. Hsueh, W. Cawthon, R. M. Harris, T. Newman, A. B. TI THE ASSOCIATION OF LENS TRANSPARENCY AND CATARACT WITH TELOMERE LENGTH IN OLDER ADULTS SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Sanders, J.; Boudreau, R.; Conley, Y.; Newman, A. B.] Univ Pittsburgh, Pittsburgh, PA USA. [Iannaccone, A.] Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA. [Hsueh, W.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Cawthon, R. M.] Univ Utah, Salt Lake City, UT USA. [Harris, T.] NIA, 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 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 266 EP 266 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006702393 ER PT J AU Perera, S Studenski, S Brach, J Wallace, RB Patel, K Guralnik, J AF Perera, S. Studenski, S. Brach, J. Wallace, R. B. Patel, K. Guralnik, J. TI PREDICTING 10-YEAR MORTALITY: A CLASSIFICATION TREE ANALYSIS OF EPESE DATA SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Perera, S.; Studenski, S.; Brach, J.] Univ Pittsburgh, Div Geriatr Med, Pittsburgh, PA USA. [Patel, K.; Guralnik, J.] NIA, Bethesda, MD 20892 USA. [Wallace, R. B.] Univ Iowa, Iowa City, IA USA. RI Perera, Subashan/D-7603-2014 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 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 294 EP 294 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006702528 ER PT J AU Espeland, MA Haan, MN Yaffe, K Gaussoin, SA Resnick, SM Rossouw, JE Shumaker, SA AF Espeland, M. A. Haan, M. N. Yaffe, K. Gaussoin, S. A. Resnick, S. M. Rossouw, J. E. Shumaker, S. A. TI RELATIONSHIP OF RETINOPATHY TO REGIONAL BRAIN VOLUMES AND COGNITIVE FUNCTION SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Espeland, M. A.; Gaussoin, S. A.] Wake Forest Univ Hlth Sci, Dept Biostat Sci, Winston Salem, NC 27109 USA. [Haan, M. N.; Yaffe, K.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Resnick, S. M.] NIA, Intramural Res Program, Baltimore, MD 21224 USA. [Rossouw, J. E.] NHLBI, Bethesda, MD 20892 USA. [Shumaker, S. A.] Wake Forest Univ Hlth Sci, Div Publ Hlth Sci, Winston Salem, NC 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 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 308 EP 308 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006702596 ER PT J AU Rapp, S Espeland, MA Manson, JE Resnick, S Bryan, NR Coker, LH Phillips, L Stefanick, ML AF Rapp, S. Espeland, M. A. Manson, J. E. Resnick, S. Bryan, N. R. Coker, L. H. Phillips, L. Stefanick, M. L. TI EDUCATIONAL ATTAINMENT, MRI CHANGES AND COGNITIVE FUNCTION IN POSTMENOPAUSAL WOMEN SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Rapp, S.] Wake Forest Univ, Sch Med, Dept Psychiat, Winston Salem, NC 27109 USA. [Espeland, M. A.] Wake Forest Univ, Sch Med, Dept Biostat, Winston Salem, NC 27109 USA. [Manson, J. E.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Resnick, S.] NIA, Baltimore, MD 21224 USA. [Bryan, N. R.] Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA. [Coker, L. H.] Wake Forest Univ, Sch Med, Dept Social Sci & Hlth Policy, Winston Salem, NC 27109 USA. [Phillips, L.] Emory Univ, Dept Internal Med, Atlanta, GA 30322 USA. [Stefanick, M. L.] Stanford Univ, Stanford Prevent Ctr, Stanford, CA 94305 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 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 308 EP 308 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006702597 ER PT J AU Chiles, N Phillips, CL Guralnik, J Patel, K AF Chiles, N. Phillips, C. L. Guralnik, J. Patel, K. TI DIABETES, PERIPHERAL NERVE FUNCTION, AND PHYSICAL FUNCTION IN OLDER ADULTS SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Chiles, N.] Univ Maryland, Baltimore, MD 21201 USA. [Phillips, C. L.; Guralnik, J.; Patel, K.] NIA, Lab Epidemiol Demog & Biometry, 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 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 335 EP 336 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006702724 ER PT J AU Bandinelli, S Corsi, A Lauretani, F Vazzana, R Kisialiou, A Milaneschi, Y Guralnik, J Ferrucci, L AF Bandinelli, S. Corsi, A. Lauretani, F. Vazzana, R. Kisialiou, A. Milaneschi, Y. Guralnik, J. Ferrucci, L. TI OLIVE OIL INTAKE AND LONGEVITY IN OLDER ITALIANS SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Bandinelli, S.] Azienda Sanitaria Firenze, Florence, Italy. [Corsi, A.; Lauretani, F.; Kisialiou, A.] Tuscany Hlth Reg Agcy, Florence, Italy. [Milaneschi, Y.; Ferrucci, L.] NIA, Baltimore, MD 21224 USA. [Vazzana, R.] Univ G DAnnunzio, Chieti, Italy. [Guralnik, J.] NIA, 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 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 339 EP 339 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006702739 ER PT J AU Milaneschi, Y Shardell, M Corsi, A Vazzana, R Bandinelli, S Guralnik, J Ferrucci, L AF Milaneschi, Y. Shardell, M. Corsi, A. Vazzana, R. Bandinelli, S. Guralnik, J. Ferrucci, L. TI VITAMIN D AND AND RISK OF ELEVATED DEPRESSIVE SYMPTOMS IN OLDER PERSONS: THE INCHIANTI STUDY SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Milaneschi, Y.; Ferrucci, L.] NIA, Baltimore, MD 21224 USA. [Shardell, M.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Corsi, A.] Tuscany Hlth Reg Agcy, Florence, Italy. [Vazzana, R.] Univ G DAnnunzio, Chieti, Italy. [Bandinelli, S.] Azienda Sanitaria Firenze, Florence, Italy. [Guralnik, J.] NIA, 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 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 339 EP 339 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006702740 ER PT J AU Patel, K Vidal, J Garcia, M Eiriksdottir, G Gudnason, V Harrris, TB Launer, LJ AF Patel, K. Vidal, J. Garcia, M. Eiriksdottir, G. Gudnason, V. Harrris, T. B. Launer, L. J. TI RED CELL DISTRIBUTION WIDTH AND BRAIN TISSUE VOLUMES, CEREBRAL INFARCTS, AND COGNITIVE FUNCTION SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Patel, K.; Vidal, J.; Garcia, M.; Harrris, T. B.; Launer, L. J.] NIA, Bethesda, MD 20892 USA. [Eiriksdottir, G.; Gudnason, V.] Iceland Heart Assoc, Kopavogur, Iceland. [Gudnason, V.] Univ Iceland, Reykjavik, Iceland. RI Gudnason, Vilmundur/K-6885-2015 OI Gudnason, Vilmundur/0000-0001-5696-0084 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 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 340 EP 340 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006702743 ER PT J AU Sellars, B Watson, NL Spencer, S Rooks, RN Rubin, S Satterfield, S Harris, TB Newman, AB AF Sellars, B. Watson, N. L. Spencer, S. Rooks, R. N. Rubin, S. Satterfield, S. Harris, T. B. Newman, A. B. TI THE INFLUENCE OF SOCIAL SUPPORT AND REGION ON CO-MORBIDITY AND MORTALITY: AN EXAMPLE OF THE BIOECOLOGICAL MODEL OF HUMAN DEVELOPMENT SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Sellars, B.; Watson, N. L.; Newman, A. B.] Univ Pittsburgh, Pittsburgh, PA USA. [Spencer, S.] Univ S Carolina, Columbia, SC 29208 USA. [Rooks, R. N.] Univ Colorado, Denver, CO 80202 USA. [Rubin, S.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Satterfield, S.] Univ Tennessee, Memphis, TN USA. [Harris, T. B.] NIA, Bethesda, MD 20892 USA. 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 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 406 EP 406 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006703185 ER PT J AU Sheu, Y Newman, AB Cawthon, P Harris, T Tylavsky, FA Cauley, JA AF Sheu, Y. Newman, A. B. Cawthon, P. Harris, T. Tylavsky, F. A. Cauley, J. A. TI BONE AGE-A NOVEL INDEX OF AGE BASED ON BONE MINERAL DENSITY SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Sheu, Y.; Newman, A. B.; Cauley, J. A.] Univ Pittsburgh, Pittsburgh, PA USA. [Cawthon, P.] Calif Pacific Med Ctr, San Francisco, CA USA. [Harris, T.] NIH, Bethesda, MD 20892 USA. [Tylavsky, F. A.] Univ Tennessee, Memphis, TN 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 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 413 EP 414 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006703219 ER PT J AU Newman, AB Boudreau, R Arnold, A Fried, LF Cauley, JA Harris, T AF Newman, A. B. Boudreau, R. Arnold, A. Fried, L. F. Cauley, J. A. Harris, T. TI RATES OF AGING-CROSS-SYSTEM CORRELATIONS AND MORTALITY RISK SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Newman, A. B.] Sch Med, Pittsburgh, PA USA. [Newman, A. B.] Univ Pittsburgh, Grad Sch Publ Hlth, Div Geriatr Med, Pittsburgh, PA USA. [Arnold, A.] Univ Washington, Seattle, WA 98195 USA. [Harris, T.] NIA, Bethesda, MD 20892 USA. 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 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 414 EP 414 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006703221 ER PT J AU Bellizzi, K Reeve, B AF Bellizzi, K. Reeve, B. TI A PROSPECTIVE STUDY OF THE IMPACT OF CANCER ON HEALTH AND FUNCTION OF OLDER CANCER SURVIVORS SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Bellizzi, K.] UConn, HDFS, Storrs, CT USA. [Reeve, B.] NCI, 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 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 415 EP 415 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006703225 ER PT J AU Ashida, S Hadley, D Giroux, A Skapinsky, K Devlin, H Koehly, LM AF Ashida, S. Hadley, D. Giroux, A. Skapinsky, K. Devlin, H. Koehly, L. M. TI SOCIAL ROLES OF OLDER MEMBERS WITHIN THE SOCIAL NETWORK SYSTEMS OF FAMILIES AFFECTED BY A HEREDITARY CANCER SYNDROME SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Ashida, S.; Hadley, D.; Giroux, A.; Skapinsky, K.; Devlin, H.; Koehly, L. M.] NHGRI, NIH, Bethesda, MD 20892 USA. [Devlin, H.] Coll New Jersey, Ewing, NJ USA. 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 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 431 EP 431 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006703308 ER PT J AU Rosano, C Aizenstein, H Venkatraman, V Taylor, C Yaffe, K Harris, T Kritchevsky, SB Newman, AB AF Rosano, C. Aizenstein, H. Venkatraman, V. Taylor, C. Yaffe, K. Harris, T. Kritchevsky, S. B. Newman, A. B. TI COVERT BRAIN CHARACTERISTICS OF PARKINSONIAN SIGNS: A DIFFUSION TENSOR IMAGING STUDY OF THE HEALTH AGING AND BODY COMPOSITION (HEALTH ABC) COHORT SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Rosano, C.; Aizenstein, H.; Venkatraman, V.; Taylor, C.; Newman, A. B.] Univ Pittsburgh, Pittsburgh, PA USA. [Yaffe, K.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Harris, T.] NIH, Bethesda, MD 20892 USA. [Kritchevsky, S. B.] Wake Forest Univ, Winston Salem, NC 27109 USA. 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 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 436 EP 436 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006703332 ER PT J AU Alley, D Hsu, F Walkup, MP Shardell, M Pahor, M Studenski, S Guralnik, J Harris, T AF Alley, D. Hsu, F. Walkup, M. P. Shardell, M. Pahor, M. Studenski, S. Guralnik, J. Harris, T. TI EFFECT OF PHYSICAL ACTIVITY ON HOSPITALIZATION-ASSOCIATED FUNCTIONAL DECLINE: THE LIFE PILOT STUDY SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Alley, D.; Shardell, M.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Hsu, F.; Walkup, M. P.] Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. [Pahor, M.] Univ Florida, Gainesville, FL USA. [Studenski, S.] Univ Pittsburgh, Pittsburgh, PA USA. [Guralnik, J.; Harris, T.] NIA, 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 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 439 EP 439 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006703347 ER PT J AU Koster, A Bankoski, A McClain, JJ Brychta, RJ Caserotti, P Harris, T AF Koster, A. Bankoski, A. McClain, J. J. Brychta, R. J. Caserotti, P. Harris, T. TI SEDENTARY PATTERNS ASSOCIATED WITH METABOLIC SYNDROME INDEPENDENT OF PHYSICAL ACTIVITY SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Koster, A.; Bankoski, A.; Caserotti, P.; Harris, T.] NIA, Bethesda, MD 20892 USA. [McClain, J. J.] NCI, Bethesda, MD 20892 USA. [Brychta, R. J.] NIDDKD, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 440 EP 440 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006703349 ER PT J AU Szanton, SL Tanner, E Agree, E Boyd, C Weiss, C Guralnik, J Gitlin, LN AF Szanton, S. L. Tanner, E. Agree, E. Boyd, C. Weiss, C. Guralnik, J. Gitlin, L. N. TI A MULTI-COMPONENT PILOT TO ENHANCE AGING-IN-PLACE CAPACITY FOR LOW-INCOME OLDER ADULTS SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Szanton, S. L.; Tanner, E.; Agree, E.; Boyd, C.; Weiss, C.] Johns Hopkins Univ, Sch Nursing, Baltimore, MD USA. [Guralnik, J.] NIA, Bethesda, MD 20892 USA. [Gitlin, L. N.] Thomas Jefferson Univ, Philadelphia, PA 19107 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 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 465 EP 465 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006703465 ER PT J AU Lin, FR Metter, E O'Brien, RJ Resnick, S Zonderman, AB Ferrucci, L AF Lin, F. R. Metter, E. O'Brien, R. J. Resnick, S. Zonderman, A. B. Ferrucci, L. TI HEARING LOSS AND INCIDENT DEMENTIA SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Metter, E.; Resnick, S.; Zonderman, A. B.; Ferrucci, L.] NIA, Baltimore, MD 21224 USA. [O'Brien, R. J.] Johns Hopkins Sch Med, Baltimore, MD USA. [Lin, F. R.] Johns Hopkins, Otolaryngol Head & Neck Surg, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 3 U2 8 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 543 EP 544 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006703833 ER PT J AU Chinnasamy, N Davis, JL Rao, M Schrump, DS Speiser, DE Rosenberg, SA Morgan, RA AF Chinnasamy, Nachimuthu Davis, Jeremy L. Rao, Mahadev Schrump, David S. Speiser, Daniel E. Rosenberg, Steven A. Morgan, Richard A. TI Development of HLA-A2 Restricted TCR Against Cancer Testis Antigen SSX-2 for Adoptive Immunotherapy of Cancer SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract C1 [Chinnasamy, Nachimuthu; Davis, Jeremy L.; Rao, Mahadev; Schrump, David S.; Rosenberg, Steven A.; Morgan, Richard A.] NCI, Surg Branch, Bethesda, MD 20892 USA. [Speiser, Daniel E.] Univ Lausanne Hosp, Ludwig Inst Canc Res Ltd, Lausanne, Switzerland. RI Speiser, Daniel/F-2173-2013 NR 0 TC 1 Z9 1 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD OCT PY 2010 VL 33 IS 8 BP 860 EP 860 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 653XQ UT WOS:000282131800017 ER PT J AU Lagisetty, KH Burns, W Zheng, ZL Rosenberg, SA Morgan, RA AF Lagisetty, Kiran H. Burns, William Zheng, Zhili Rosenberg, Steven A. Morgan, Richard A. TI Development of a Chimeric Antigen Receptor for Prostate Cancer Stem Cell Antigen for Adoptive Cell Therapy of Cancer SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract C1 [Lagisetty, Kiran H.; Zheng, Zhili; Rosenberg, Steven A.; Morgan, Richard A.] NCI, Surg Branch, Bethesda, MD 20892 USA. [Burns, William] Johns Hopkins Med, Dept Surg, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD OCT PY 2010 VL 33 IS 8 BP 862 EP 862 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 653XQ UT WOS:000282131800022 ER PT J AU Yang, SC Zhang, L Zheng, ZL Park, T Rosenberg, SA Morgan, RA AF Yang, Shicheng Zhang, Ling Zheng, Zhili Park, Tristen Rosenberg, Steven A. Morgan, Richard A. TI Generating Potent Anti-Tumor CD62Lhigh CD8+T Cells for Adoptive Immunotherapy SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract C1 [Yang, Shicheng; Zhang, Ling; Zheng, Zhili; Park, Tristen; Rosenberg, Steven A.; Morgan, Richard A.] Natl Canc Inst, Surg Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD OCT PY 2010 VL 33 IS 8 BP 866 EP 867 PG 2 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 653XQ UT WOS:000282131800036 ER PT J AU Zhang, L Abate-Daga, D Davis, JL Chinnasamy, N Rosenberg, SA Morgan, RA AF Zhang, Ling Abate-Daga, Daniel Davis, Jeremy L. Chinnasamy, Nachimuthu Rosenberg, Steven A. Morgan, Richard A. TI Improving Adoptive Cell Therapy by Blocking the TGF beta Pathway at the Tumor Environment SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract C1 [Zhang, Ling; Abate-Daga, Daniel; Davis, Jeremy L.; Chinnasamy, Nachimuthu; Rosenberg, Steven A.; Morgan, Richard A.] NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD OCT PY 2010 VL 33 IS 8 BP 867 EP 867 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 653XQ UT WOS:000282131800037 ER PT J AU Zheng, ZL Morgan, RA AF Zheng, Zhili Morgan, Richard A. TI Protein L: A Novel Reagent for Universal Detection of Chimeric Antigen Receptor (CAR) Expression by Flow Cytometry SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract C1 [Zheng, Zhili; Morgan, Richard A.] Natl Inst Hlth, Surg Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD OCT PY 2010 VL 33 IS 8 BP 867 EP 867 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 653XQ UT WOS:000282131800038 ER PT J AU Greten, TF Hoechst, B Zhao, F Gamrekelashvili, J Manns, M Korangy, F AF Greten, Tim F. Hoechst, Bastian Zhao, Fei Gamrekelashvili, Jaba Manns, Michael Korangy, Firouzeh TI Induction of Different CD4+T Cell Subsets by HLA-DR-Myeloid Derived Suppressor Cells and CD14+HLA-DR+ Monocytes SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract C1 [Greten, Tim F.; Hoechst, Bastian; Zhao, Fei; Gamrekelashvili, Jaba; Manns, Michael; Korangy, Firouzeh] Hannover Med Sch, D-3000 Hannover, Germany. [Greten, Tim F.; Zhao, Fei; Gamrekelashvili, Jaba; Korangy, Firouzeh] NCI, Med Oncol Brnach, NIH, Bethesda, MD USA. RI Greten, Tim/B-3127-2015 OI Greten, Tim/0000-0002-0806-2535 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD OCT PY 2010 VL 33 IS 8 BP 869 EP 869 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 653XQ UT WOS:000282131800044 ER PT J AU Samara, RN Dong, YJ Abdalla, M Mkrtichyan, M Ozbun, L Jiang, YF Qian, JH Khleif, S AF Samara, Raed N. Dong, Yujun Abdalla, Maher Mkrtichyan, Mikayel Ozbun, Laurent Jiang, Yufei Qian, Jiahua Khleif, Samir TI CD4+Foxp3+Regulatory T Cells are Dependent on PI3K Pathway Allowing for Their Selective Inhibition SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract C1 [Samara, Raed N.; Dong, Yujun; Abdalla, Maher; Mkrtichyan, Mikayel; Ozbun, Laurent; Jiang, Yufei; Qian, Jiahua; Khleif, Samir] NCI, Vaccine Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD OCT PY 2010 VL 33 IS 8 BP 873 EP 873 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 653XQ UT WOS:000282131800056 ER PT J AU Castiello, L Finn, MW Marincola, FM Krensky, AM Clayberger, C Stroncek, DF Sabatino, M AF Castiello, Luciano Finn, Michael W. Marincola, Francesco M. Krensky, Alan M. Clayberger, Carol Stroncek, David F. Sabatino, Marianna TI Global Gene Expression Analysis of 15 kD Granulysin Stimulated Monocytes Compared to GM-CSF SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract C1 [Castiello, Luciano; Marincola, Francesco M.; Stroncek, David F.; Sabatino, Marianna] NCI, Dept Transfus Med, NIH, Washington, DC USA. [Finn, Michael W.; Krensky, Alan M.; Clayberger, Carol] NCI, Lab Cellular & Mol Biol, NIH, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD OCT PY 2010 VL 33 IS 8 BP 875 EP 875 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 653XQ UT WOS:000282131800061 ER PT J AU Thomas, JM Pos, Z Wang, RY Wang, E Lussow, P Alter, HJ Marincola, FM AF Thomas, Jaime M. Pos, Zoltan Wang, Richard Y. Wang, Ena Lussow, Paolo Alter, Harvey J. Marincola, Francesco M. TI High-Throughput Analysis of Plasmacytoid Dendritic Cells Reveals Differential Responses to Discrete Viral Entities SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract C1 [Thomas, Jaime M.; Pos, Zoltan; Wang, Richard Y.; Wang, Ena; Alter, Harvey J.; Marincola, Francesco M.] NIH, Dept Transfus Med, Infect Dis & Immunogenet Sect, Ctr Clin, Bethesda, MD 20892 USA. [Lussow, Paolo] NIAID, Immunoregulat Lab, Immunopathogenesis Sect, 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 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD OCT PY 2010 VL 33 IS 8 BP 880 EP 880 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 653XQ UT WOS:000282131800077 ER PT J AU Forget, MA Turcotte, S Lapointe, R AF Forget, Marie-Andree Turcotte, Simon Lapointe, Rejean TI Immune Response Against DKK1 in Common Cancers SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract C1 [Forget, Marie-Andree; Lapointe, Rejean] Ctr Hosp Univ Montreal CRCHUM, Montreal, PQ, Canada. [Forget, Marie-Andree; Lapointe, Rejean] Univ Montreal, Inst Canc Montreal, Montreal, PQ H2L 4M1, Canada. [Turcotte, Simon] 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 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD OCT PY 2010 VL 33 IS 8 BP 896 EP 896 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 653XQ UT WOS:000282131800129 ER PT J AU Jiang, Q Weiss, JM Ortaldo, JR Back, T Guichard, S Thakurta, A Wiltrout, RH AF Jiang, Qun Weiss, Jonathan M. Ortaldo, John R. Back, Timothy Guichard, Sylvie Thakurta, Anjan Wiltrout, Robert H. TI Enhanced Anti-tumor Effect of Combination Therapy With Anti-CD40 Antibody and the mTOR Kinase Inhibitor AZD8055 SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract C1 [Jiang, Qun; Weiss, Jonathan M.; Ortaldo, John R.; Back, Timothy; Wiltrout, Robert H.] NCI, Frederick, MD 21701 USA. [Guichard, Sylvie; Thakurta, Anjan] AstraZeneca, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD OCT PY 2010 VL 33 IS 8 BP 898 EP 898 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 653XQ UT WOS:000282131800136 ER PT J AU Maccalli, C Di Tomaso, T Wang, E Mazzoleni, S Sovena, G Galli, R Marincola, FM Parmiani, G AF Maccalli, Cristina Di Tomaso, Tiziano Wang, Ena Mazzoleni, Stefania Sovena, Gloria Galli, Rossella Marincola, Francesco M. Parmiani, Giorgio TI Immunomodulation of T Cell-Mediated Activity by Cancer Stem Cells Isolated from Human Glioblastoma SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract C1 [Mazzoleni, Stefania; Galli, Rossella] San Raffaele Fdn Sci Inst, Neural Stem Cell Unit, Milan, Italy. [Wang, Ena; Marincola, Francesco M.] NIH, Dept Transfus Med, 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 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD OCT PY 2010 VL 33 IS 8 BP 902 EP 902 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 653XQ UT WOS:000282131800146 ER PT J AU OEntas, RJ Wellstein, A Morgan, RA Mackall, CL AF Oentas, Rimas J. Wellstein, Anton Morgan, Richard A. Mackall, Crystal L. TI Designing a New Chimeric Antigen Receptor for the Tumor Antigen ALK SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract C1 [Oentas, Rimas J.; Mackall, Crystal L.] NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. [Morgan, Richard A.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. [Wellstein, Anton] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD OCT PY 2010 VL 33 IS 8 BP 905 EP 905 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 653XQ UT WOS:000282131800157 ER PT J AU Rossi, GR Vahanian, NN Morris, JC Malyguine, A Strobl, S Tennant, L Ramsey, J Link, CJ AF Rossi, Gabriela R. Vahanian, Nicholas N. Morris, John C. Malyguine, Anatoli Strobl, Susan Tennant, Lucinda Ramsey, Jay Link, Charles J. TI Immunological Findings in a Phase II Immunotherapy Study Using Allogeneic Lung Cancer Cells Modified to Express Alpha(1,3)Gal Epitopes in Patients with Advanced Non-Small Cell Lung Cancer SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract C1 [Rossi, Gabriela R.; Vahanian, Nicholas N.; Tennant, Lucinda; Ramsey, Jay; Link, Charles J.] NewLink Genet, Tumor Immunol, Ames, IA USA. [Morris, John C.] NCI, Metab Branch, Bethesda, MD 20892 USA. [Malyguine, Anatoli; Strobl, Susan] SAIC, CMI, 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 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD OCT PY 2010 VL 33 IS 8 BP 908 EP 908 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 653XQ UT WOS:000282131800164 ER PT J AU Taylor, J Mossoba, ME Massey, PR Onda, M Pastan, I Fowler, DH AF Taylor, Justin Mossoba, Miriam E. Massey, Paul R. Onda, Masanori Pastan, Ira Fowler, Daniel H. TI Pentostatin Plus Cyclophosphamide to Eliminate Immunogenicity of Anti-Mesothelin Immunotoxin (SS1P) SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract C1 [Taylor, Justin; Mossoba, Miriam E.; Massey, Paul R.; Onda, Masanori; Pastan, Ira; Fowler, Daniel H.] Natl Canc Inst, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD OCT PY 2010 VL 33 IS 8 BP 911 EP 911 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 653XQ UT WOS:000282131800173 ER PT J AU Wang, E Gogas, H Monaco, A Uccellini, L Floudas, CS Metaxas, Y Dafni, U Fountzilas, G Spyropoulou-Vlachou, M Marincola, FM AF Wang, Ena Gogas, Helen Monaco, Alessandro Uccellini, Lorenzo Floudas, Charalampos S. Metaxas, Yanis Dafni, Urania Fountzilas, George Spyropoulou-Vlachou, Maria Marincola, Francesco M. TI Evaluation of FOXP3 Microsatellite Polymorphisms in High-Risk Melanoma Patients Receiving Adjuvant Interferon SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract C1 [Wang, Ena; Monaco, Alessandro; Uccellini, Lorenzo; Marincola, Francesco M.] NIH, Dept Transfus Med, Bethesda, MD 20892 USA. [Gogas, Helen; Floudas, Charalampos S.; Metaxas, Yanis; Dafni, Urania; Fountzilas, George; Spyropoulou-Vlachou, Maria] Hellen Cooperat Oncol Grp, Athens, Greece. RI Monaco, Alessandro/O-5338-2015 OI Monaco, Alessandro/0000-0002-9941-7003 NR 0 TC 0 Z9 0 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD OCT PY 2010 VL 33 IS 8 BP 912 EP 912 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 653XQ UT WOS:000282131800176 ER PT J AU Zhang, YJ Hansen, JK Xiang, LM Kawa, S Onda, M Ho, M Hassan, R Pastan, I AF Zhang, Yujian Hansen, Johanna K. Xiang, Laiman Kawa, Seiji Onda, Masanori Ho, Mitchell Hassan, Raffit Pastan, Ira TI A Flow Cytometry Method to Quantitate Internalized Immunotoxins In Vivo Explains Taxol and Immunotoxin Synergy SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract C1 [Zhang, Yujian; Hansen, Johanna K.; Xiang, Laiman; Kawa, Seiji; Onda, Masanori; Ho, Mitchell; Hassan, Raffit; Pastan, Ira] NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD OCT PY 2010 VL 33 IS 8 BP 914 EP 914 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 653XQ UT WOS:000282131800183 ER PT J AU Shears, SB AF Shears, S. B. TI CLC3 AND THE REGULATION OF TRANSMEMBRANE CHLORIDE ION FLUXES BY INOSITOL PHOSPHATES SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 [Shears, S. B.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD OCT PY 2010 VL 115 SU 1 BP 60 EP 60 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 649YS UT WOS:000281812600158 ER PT J AU Fujita, T Goldman-Nedergaard, N Chen, M Xu, Q Peng, W Liu, W Jensen, T Pei, Y Wang, F Han, X Chen, JF Schnermann, J Takano, T Bekar, L Tieu, K Nedergaard, M AF Fujita, T. Goldman-Nedergaard, N. Chen, M. Xu, Q. Peng, W. Liu, W. Jensen, T. Pei, Y. Wang, F. Han, X. Chen, J. F. Schnermann, J. Takano, T. Bekar, L. Tieu, K. Nedergaard, M. TI ADENOSINE A1 RECEPTORS MEDIATE LOCAL ANTI-NOCICEPTIVE EFFECTS OF ACUPUNCTURE SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 [Fujita, T.; Goldman-Nedergaard, N.; Chen, M.; Xu, Q.; Peng, W.; Liu, W.; Jensen, T.; Pei, Y.; Wang, F.; Han, X.; Takano, T.; Bekar, L.; Tieu, K.; Nedergaard, M.] Univ Rochester, Med Ctr, Ctr Translat Neuromed, Rochester, NY USA. [Chen, J. F.] Boston Univ, Sch Med, Dept Neurol, Boston, MA USA. [Schnermann, J.] NIDDK, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 10 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD OCT PY 2010 VL 115 SU 1 BP 76 EP 76 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 649YS UT WOS:000281812600199 ER PT J AU Anderson, NLR Andrews, M Bent, KN Douglas, MK Elhammoumi, CV Keenan, C Kemppainen, JK Lipson, JG Martin, CT Mattson, S AF Anderson, Nancy L. R. Andrews, Margaret Bent, Katherine N. Douglas, Marilyn K. Elhammoumi, Cheryl V. Keenan, Colleen Kemppainen, Jeanne K. Lipson, Juliene G. Martin, Carolyn Thompson Mattson, Susan TI Culturally Based Health and Illness Beliefs and Practices Across the Life Span SO JOURNAL OF TRANSCULTURAL NURSING LA English DT Article C1 [Douglas, Marilyn K.; Lipson, Juliene G.] Univ Calif San Francisco, Sch Nursing, San Francisco, CA 94143 USA. [Anderson, Nancy L. R.; Keenan, Colleen] Univ Calif Los Angeles, Sch Nursing, Los Angeles, CA 90024 USA. [Andrews, Margaret] Univ Michigan Flint, Sch Hlth Profess & Studies, Flint, MI USA. [Bent, Katherine N.] NIH, Healthcare Delivery & Methodol Integrated Review, Bethesda, MD 20892 USA. [Elhammoumi, Cheryl V.] E Carolina Univ, Coll Nursing, Greenville, NC USA. [Martin, Carolyn Thompson] Univ N Carolina, Wilmington, NC 28401 USA. Calif State Univ Stanislaus, Turlock, CA 95382 USA. Arizona State Univ, Tempe, AZ USA. RP Douglas, MK (reprint author), Univ Calif San Francisco, Sch Nursing, San Francisco, CA 94143 USA. EM martydoug@comcast.net FU California Endowment [20082226]; Health Resources and Services Administration [D11 HPO9759] FX The California Endowment (grant number 20082226) and Health Resources and Services Administration (grant number D11 HPO9759). NR 0 TC 2 Z9 2 U1 2 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1043-6596 J9 J TRANSCULT NURS JI J. Transcult. Nurs. PD OCT PY 2010 VL 21 IS 4 SU 1 BP 152S EP 235S DI 10.1177/1043659610381094 PG 84 WC Nursing SC Nursing GA 672LV UT WOS:000283585800006 ER PT J AU Plenz, D AF Plenz, Dietmar TI THEORETICAL NEUROSCIENCE A leak-proof model SO NATURE PHYSICS LA English DT News Item ID NEURONAL AVALANCHES; NETWORKS C1 NIMH, Sect Crit Brain Dynam, Porter Neurosci Res Ctr, Bethesda, MD 20892 USA. RP Plenz, D (reprint author), NIMH, Sect Crit Brain Dynam, Porter Neurosci Res Ctr, Bethesda, MD 20892 USA. EM plenzd@mail.nih.gov NR 9 TC 2 Z9 2 U1 0 U2 7 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1745-2473 J9 NAT PHYS JI Nat. Phys. PD OCT PY 2010 VL 6 IS 10 BP 717 EP 718 PG 2 WC Physics, Multidisciplinary SC Physics GA 672GC UT WOS:000283570000003 ER PT J AU Cofield, SS Conwit, R Barsan, W Quinn, J AF Cofield, Stacey S. Conwit, Robin Barsan, William Quinn, James TI Recruitment and Retention of Patients into Emergency Medicine Clinical Trials SO ACADEMIC EMERGENCY MEDICINE LA English DT Article DE emergency medicine; clinical trials ID PILOT DOSE-ESCALATION; ACUTE ISCHEMIC-STROKE; ADVANCED LIFE-SUPPORT; DEPARTMENT VISITS; FOLLOW-UP; INFORMED-CONSENT; RANDOMIZED-TRIAL; CARDIAC-ARREST; SEPTIC SHOCK; ENROLLMENT AB The emergency medicine (EM) and prehospital environments are unlike any other clinical environments and require special consideration to allow the successful implementation of clinical trials. This article reviews the specific issues involved in EM clinical trials and provides strategies from EM and non-EM trials to maximize recruitment and retention. While the evidence supporting some of these strategies is deficient, addressing recruitment and retention issues with specific strategies will help researchers deal with these issues in their funding applications and in turn develop the necessary infrastructure to participate in EM clinical trials. ACADEMIC EMERGENCY MEDICINE 2010; 17:1104-1112 (C) 2010 by the Society for Academic Emergency Medicine. C1 [Quinn, James] Stanford Univ, Div Emergency Med, Palo Alto, CA 94304 USA. [Cofield, Stacey S.] Univ Alabama, Dept Biostat, Birmingham, AL 35294 USA. [Conwit, Robin] NINDS, NIH, Silver Spring, MD USA. [Barsan, William] Univ Michigan, Dept Emergency Med, Ann Arbor, MI 48109 USA. RP Quinn, J (reprint author), Stanford Univ, Div Emergency Med, Palo Alto, CA 94304 USA. EM quinnj@stanford.edu FU NINDS NIH HHS [U10 NS058929, U10 NS058929-03] NR 64 TC 11 Z9 11 U1 1 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD OCT PY 2010 VL 17 IS 10 BP 1104 EP 1112 DI 10.1111/j.1553-2712.2010.00866.x PG 9 WC Emergency Medicine SC Emergency Medicine GA 663IR UT WOS:000282877400011 PM 21040112 ER PT J AU Summers, RM AF Summers, Ronald M. TI Dose Reduction in CT: The Time Is Now SO ACADEMIC RADIOLOGY LA English DT Editorial Material ID CANCER-RISKS; RADIATION PROTECTION; COMPUTED-TOMOGRAPHY; CROHNS-DISEASE; IMAGE QUALITY; EXPOSURE C1 NIH, Bethesda, MD 20892 USA. RP Summers, RM (reprint author), NIH, Clin Ctr Bldg 10 Room 1C368X MSC 1182, Bethesda, MD 20892 USA. EM rms@nih.gov FU Intramural NIH HHS [ZIA CL040004-07] NR 24 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 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD OCT PY 2010 VL 17 IS 10 BP 1201 EP 1202 DI 10.1016/j.acra.2010.08.001 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 653PQ UT WOS:000282109500001 PM 20832022 ER PT J AU Stains, CI Furman, JL Porter, JR Rajagopal, S Li, YX Wyatt, RT Ghosh, I AF Stains, Cliff I. Furman, Jennifer L. Porter, Jason R. Rajagopal, Srivats Li, Yuxing Wyatt, Richard T. Ghosh, Indraneel TI A General Approach for Receptor and Antibody-Targeted Detection of Native Proteins Utilizing Split-Luciferase Reassembly SO ACS CHEMICAL BIOLOGY LA English DT Article ID FRAGMENT COMPLEMENTATION ASSAYS; GREEN FLUORESCENT PROTEIN; IN-VIVO; MONOCLONAL-ANTIBODY; CRYSTAL-STRUCTURE; LIVING SUBJECTS; CANCER-THERAPY; BREAST-CANCER; CD4 RECEPTOR; COMPLEX AB The direct detection of native proteins in heterogeneous solutions remains a challenging problem. Standard methodologies rely on a separation step to circumvent nonspecific signal generation, We hypothesized that a simple and general method for the detection of native proteins in solution could be achieved through ternary complexation, where the conditional signal generation afforded by split-protein reporters could be married to the specificity afforded by either native receptors or specific antibodies. Toward this goal, we describe a solution phase split-luciferase assay for native protein detection, where we fused fragmented halves of firefly luciferase to separate receptor fragments or single-chain antibodies, allowing for conditional luciferase complementation in the presence of several biologically significant protein targets. To demonstrate the utility of this strategy, we have developed and validated assay platforms for the vascular endothelial growth factor, the gp120 coat protein from HIV-1, and the human epidermal growth factor receptor 2 (HER2), a marker for breast cancer. The specificities of the recognition elements, CD4 and the 17b single-chain antibody, employed in the gp120 sensor allowed us to parse gp120s from different clades. Our rationally designed HER2 sensing platform was capable of discriminating between HER2 expression levels in several tumor cell lines. In addition, luminescence from reassembled luciferase was linear across a panel of cell lines with increasing HER2 expression. We envision that the proof of principle studies presented herein may allow for the potential detection of a broad range of biological analytes utilizing ternary split-protein systems. C1 [Stains, Cliff I.; Furman, Jennifer L.; Porter, Jason R.; Rajagopal, Srivats; Ghosh, Indraneel] Univ Arizona, Dept Chem & Biochem, Tucson, AZ 85721 USA. [Li, Yuxing; Wyatt, Richard T.] NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. RP Ghosh, I (reprint author), Univ Arizona, Dept Chem & Biochem, 1306 E Univ Blvd, Tucson, AZ 85721 USA. EM ghosh@email.arizona.edu RI Li, Yuxing/E-6696-2015 OI Li, Yuxing/0000-0001-6035-1206 FU National Institutes of Health (NIH) [5T32GM008804-05, R01AI068414] FX J.L.F. and J.R.P. were supported by a National Institutes of Health Institutional Training Grant (5T32GM008804-05). We thank the NIH for support (R01AI068414). We thank P. Longo, K. Block, and B. Fritz for helpful discussions; S. Rana for initial Flt-1 constructs, B. Olenyuk for providing the MCF7 cell line, D. Leahy for providing the HER2 ECD expressing Led l cell line, and the NIH AIDS repository for HIV-1 reagents. NR 60 TC 16 Z9 16 U1 0 U2 21 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1554-8929 J9 ACS CHEM BIOL JI ACS Chem. Biol. PD OCT PY 2010 VL 5 IS 10 BP 943 EP 952 DI 10.1021/cb100143m PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 663XW UT WOS:000282924500005 PM 20681584 ER PT J AU Nuss, JE Dong, YX Wanner, LM Ruthel, G Wipf, P Gussio, R Vennerstrom, JL Bavari, S Burnett, JC AF Nuss, Jonathan E. Dong, Yuxiang Wanner, Laura M. Ruthel, Gordon Wipf, Peter Gussio, Rick Vennerstrom, Jonathan L. Bavari, Sina Burnett, James C. TI Pharmacophore Refinement Guides the Design of Nanomolar-Range Botulinum Neurotoxin Serotype A Light Chain Inhibitors SO ACS MEDICINAL CHEMISTRY LETTERS LA English DT Article DE Botulinum neurotoxin; small molecule inhibitor; gas-phase pharmacophore; rational design; biothreat agent ID PROTEOLYTIC ACTIVITY; ANALOGS; BINDING; TOXIN AB Botulinum neurotoxins (BoNTs) are the deadliest of microbial toxins. The enzyme's zinc(II) metalloprotease, referred to as the light chain (LC) component, inhibits acetylcholine release into neuromuscular junctions, resulting in the disease botulism. Currently, no therapies counter BoNT poisoning postneuronal intoxication; however it is hypothesized that small molecules may be used to inhibit BoNT LC activity in the neuronal cytosol. Herein, we describe the pharmacophore-based design and chemical synthesis of potent [non-zinc(II) chelating] small molecule (nonpeptidic) inhibitors (SMNPIs) of the BoNT serotype-A LC (the most toxic of the BoNT serotype LCs). Specifically the three-dimensional superimpositions of 2-[4-(4-amidinephenoxy)-phenyl]indole-6-amidine-based SMNPI regionisomers [K(i) = 0.600 mu M (+/-0.100 mu M)], with a novel lead bis-[3-amide-5-(imidazolino) phenyl]terephthalamide (BAIPT)-based SMNPI [K(i) = 8.52 mu M (+/-0.53 mu M)], resulted in a refined four zone pharmacophore. The refined model guided the design of BAIPT-based SMNPIs possessing K(i) values = 0.572 (+/-0.041 mu M) and 0.900 mu M (0.078 mu M). C1 [Nuss, Jonathan E.; Wanner, Laura M.; Ruthel, Gordon; Bavari, Sina] USA, Med Res Inst Infect Dis, Frederick, MD 21702 USA. [Dong, Yuxiang; Vennerstrom, Jonathan L.] Univ Nebraska Med Ctr, Coll Pharm, Dept Pharmaceut Sci, Omaha, NE 68198 USA. [Wipf, Peter] Univ Pittsburgh, Dept Chem, Pittsburgh, PA 15260 USA. [Wipf, Peter] Univ Pittsburgh, Combinatorial Chem Ctr, Pittsburgh, PA 15260 USA. [Gussio, Rick] Natl Canc Inst Frederick, Dev Therapeut Program, Frederick, MD 21702 USA. [Burnett, James C.] Natl Canc Inst Frederick, Target Struct Based Drug Discovery Grp, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Bavari, S (reprint author), USA, Med Res Inst Infect Dis, Frederick, MD 21702 USA. EM sina.bavari@us.army.mil; burnettjames@mail.nih.gov FU Defense Threat Reduction Agency [3.10084_09_RD_B]; MRMC [Y3CM 100505]; NCI, National Institutes of Health; National Cancer Institute, National Institutes of Health [HHSN261200800001E] FX The presented research was supported by Defense Threat Reduction Agency project 3.10084_09_RD_B and also Agreement Y3CM 100505 (MRMC and NCI, National Institutes of Health) for J.C.B. Furthermore, for J.C.B.. in accordance with SAIC-Frederick. Inc., contractual requirements, this project has been funded in whole or in part with federal Funds from the National Cancer Institute, National Institutes of Health, under Contract HHSN261200800001E. NR 21 TC 12 Z9 12 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1948-5875 J9 ACS MED CHEM LETT JI ACS Med. Chem. Lett. PD OCT PY 2010 VL 1 IS 7 BP 301 EP 305 DI 10.1021/ml100056v PG 5 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 666FY UT WOS:000283100900001 PM 21116458 ER PT J AU Krishna, SS Aravind, L Bakolitsa, C Caruthers, J Carlton, D Miller, MD Abdubek, P Astakhova, T Axelrod, HL Chiu, HJ Clayton, T Deller, MC Duan, LA Feuerhelm, J Grant, JC Han, GW Jaroszewski, L Jin, KK Klock, HE Knuth, MW Kumar, A Marciano, D McMullan, D Morse, AT Nigoghossian, E Okach, L Reyes, R Rife, CL van den Bedem, H Weekes, D Xu, QP Hodgson, KO Wooley, J Elsliger, MA Deacon, AM Godzik, A Lesley, SA Wilson, IA AF Krishna, S. Sri Aravind, L. Bakolitsa, Constantina Caruthers, Jonathan Carlton, Dennis Miller, Mitchell D. Abdubek, Polat Astakhova, Tamara Axelrod, Herbert L. Chiu, Hsiu-Ju Clayton, Thomas Deller, Marc C. Duan, Lian Feuerhelm, Julie Grant, Joanna C. Han, Gye Won Jaroszewski, Lukasz Jin, Kevin K. Klock, Heath E. Knuth, Mark W. Kumar, Abhinav Marciano, David McMullan, Daniel Morse, Andrew T. Nigoghossian, Edward Okach, Linda Reyes, Ron Rife, Christopher L. van den Bedem, Henry Weekes, Dana Xu, Qingping Hodgson, Keith O. Wooley, John Elsliger, Marc-Andre Deacon, Ashley M. Godzik, Adam Lesley, Scott A. Wilson, Ian A. TI The structure of SSO2064, the first representative of Pfam family PF01796, reveals a novel two-domain zinc-ribbon OB-fold architecture with a potential acyl-CoA-binding role SO ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY AND CRYSTALLIZATION COMMUNICATIONS LA English DT Article ID DNA-BINDING; MACROMOLECULAR CRYSTALLOGRAPHY; PROTEIN CRYSTALS; DIFFRACTION DATA; GENOMICS; IDENTIFICATION; REFINEMENT; GENERATION; MECHANISM; EVOLUTION AB SSO2064 is the first structural representative of PF01796 (DUF35), a large prokaryotic family with a wide phylogenetic distribution. The structure reveals a novel two-domain architecture comprising an N-terminal, rubredoxin-like, zinc ribbon and a C-terminal, oligonucleotide/oligosaccharide-binding (OB) fold domain. Additional N-terminal helical segments may be involved in protein-protein interactions. Domain architectures, genomic context analysis and functional evidence from certain bacterial representatives of this family suggest that these proteins form a novel fatty-acid-binding component that is involved in the biosynthesis of lipids and polyketide antibiotics and that they possibly function as acyl-CoA-binding proteins. This structure has led to a re-evaluation of the DUF35 family, which has now been split into two entries in the latest Pfam release (v.24.0). C1 [Krishna, S. Sri; Astakhova, Tamara; Duan, Lian; Jaroszewski, Lukasz; Morse, Andrew T.; Wooley, John; Godzik, Adam] Univ Calif San Diego, Ctr Res Biol Syst, La Jolla, CA 92093 USA. [Krishna, S. Sri; Bakolitsa, Constantina; Jaroszewski, Lukasz; Weekes, Dana; Godzik, Adam] Burnham Inst Med Res, Program Bioinformat & Syst Biol, La Jolla, CA USA. [Aravind, L.] NIH, Bethesda, MD 20892 USA. [Caruthers, Jonathan; Miller, Mitchell D.; Axelrod, Herbert L.; Chiu, Hsiu-Ju; Jin, Kevin K.; Kumar, Abhinav; Reyes, Ron; Rife, Christopher L.; van den Bedem, Henry; Xu, Qingping; Deacon, Ashley M.] SLAC Natl Accelerator Lab, Stanford Synchrotron Radiat Lightsource, Menlo Pk, CA USA. [Carlton, Dennis; Clayton, Thomas; Deller, Marc C.; Han, Gye Won; Marciano, David; Elsliger, Marc-Andre; Lesley, Scott A.; Wilson, Ian A.] Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA. [Abdubek, Polat; Feuerhelm, Julie; Klock, Heath E.; Knuth, Mark W.; McMullan, Daniel; Nigoghossian, Edward; Okach, Linda; Lesley, Scott A.] Novartis Res Fdn, Prot Sci Dept, Genom Inst, San Diego, CA USA. EM wilson@scripps.edu RI Godzik, Adam/A-7279-2009 OI Godzik, Adam/0000-0002-2425-852X FU NIH National Institute of General Medical Sciences Protein Structure Initiative [U54 GM074898]; Department of Energy, Office of Biological and Environmental Research; National Institutes of Health; National Institutes of Health (National Center for Research Resources); National Institutes of Health (National Institute of General Medical Sciences) FX This work was supported by the NIH National Institute of General Medical Sciences Protein Structure Initiative, Grant No. U54 GM074898. Portions of this research were carried out at the Stanford Synchrotron Radiation Lightsource (SSRL). The SSRL is a national user facility operated by Stanford University on behalf of the US Department of Energy, Office of Basic Energy Sciences. The SSRL Structural Molecular Biology Program is supported by the Department of Energy, Office of Biological and Environmental Research and by the National Institutes of Health (National Center for Research Resources, Biomedical Technology Program and the National Institute of General Medical Sciences). Genomic DNA from S. solfataricus DSM 1617 (ATCC No. 35092D-5) was obtained from the American Type Culture Collection (ATCC). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of General Medical Sciences or the National Institutes of Health. NR 45 TC 7 Z9 7 U1 0 U2 10 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1744-3091 J9 ACTA CRYSTALLOGR F JI Acta Crystallogr. F-Struct. Biol. Cryst. Commun. PD OCT PY 2010 VL 66 BP 1160 EP 1166 DI 10.1107/S1744309110002514 PN 10 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA 658QA UT WOS:000282503300005 PM 20944206 ER PT J AU Miller, MD Aravind, L Bakolitsa, C Rife, CL Carlton, D Abdubek, P Astakhova, T Axelrod, HL Chiu, HJ Clayton, T Deller, MC Duan, LA Feuerhelm, J Grant, JC Han, GW Jaroszewski, L Jin, KK Klock, HE Knuth, MW Kozbial, P Krishna, SS Kumar, A Marciano, D McMullan, D Morse, AT Nigoghossian, E Okach, L Reyes, R van den Bedem, H Weekes, D Xu, QP Hodgson, KO Wooley, J Elsliger, MA Deacon, AM Godzik, A Lesley, SA Wilson, IA AF Miller, Mitchell D. Aravind, L. Bakolitsa, Constantina Rife, Christopher L. Carlton, Dennis Abdubek, Polat Astakhova, Tamara Axelrod, Herbert L. Chiu, Hsiu-Ju Clayton, Thomas Deller, Marc C. Duan, Lian Feuerhelm, Julie Grant, Joanna C. Han, Gye Won Jaroszewski, Lukasz Jin, Kevin K. Klock, Heath E. Knuth, Mark W. Kozbial, Piotr Krishna, S. Sri Kumar, Abhinav Marciano, David McMullan, Daniel Morse, Andrew T. Nigoghossian, Edward Okach, Linda Reyes, Ron van den Bedem, Henry Weekes, Dana Xu, Qingping Hodgson, Keith O. Wooley, John Elsliger, Marc-Andre Deacon, Ashley M. Godzik, Adam Lesley, Scott A. Wilson, Ian A. TI Structure of the first representative of Pfam family PF04016 (DUF364) reveals enolase and Rossmann-like folds that combine to form a unique active site with a possible role in heavy-metal chelation SO ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY AND CRYSTALLIZATION COMMUNICATIONS LA English DT Article ID CRYSTAL-STRUCTURE; MACROMOLECULAR CRYSTALLOGRAPHY; PROTEIN CRYSTALS; DIFFRACTION DATA; RESOLUTION; GENOMICS; BINDING; CONSERVATION; REFINEMENT; INSIGHTS AB The crystal structure of Dhaf4260 from Desulfitobacterium hafniense DCB-2 was determined by single-wavelength anomalous diffraction (SAD) to a resolution of 2.01 angstrom using the semi-automated high-throughput pipeline of the Joint Center for Structural Genomics (JCSG) as part of the NIGMS Protein Structure Initiative (PSI). This protein structure is the first representative of the PF04016 (DUF364) Pfam family and reveals a novel combination of two well known domains (an enolase N-terminal-like fold followed by a Rossmann-like domain). Structural and bioinformatic analyses reveal partial similarities to Rossmann-like methyltransferases, with residues from the enolase-like fold combining to form a unique active site that is likely to be involved in the condensation or hydrolysis of molecules implicated in the synthesis of flavins, pterins or other siderophores. The genome context of Dhaf4260 and homologs additionally supports a role in heavy-metal chelation. C1 [Miller, Mitchell D.; Rife, Christopher L.; Axelrod, Herbert L.; Chiu, Hsiu-Ju; Jin, Kevin K.; Kumar, Abhinav; Reyes, Ron; van den Bedem, Henry; Xu, Qingping; Deacon, Ashley M.] SLAC Natl Accelerator Lab, Stanford Synchrotron Radiat Lightsource, Menlo Pk, CA USA. [Aravind, L.] NIH, Bethesda, MD 20892 USA. [Bakolitsa, Constantina; Jaroszewski, Lukasz; Kozbial, Piotr; Krishna, S. Sri; Weekes, Dana; Godzik, Adam] Burnham Inst Med Res, Program Bioinformat & Syst Biol, La Jolla, CA USA. [Carlton, Dennis; Clayton, Thomas; Deller, Marc C.; Han, Gye Won; Marciano, David; Elsliger, Marc-Andre; Lesley, Scott A.; Wilson, Ian A.] Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA. [Abdubek, Polat; Feuerhelm, Julie; Grant, Joanna C.; Klock, Heath E.; Knuth, Mark W.; McMullan, Daniel; Nigoghossian, Edward; Okach, Linda; Lesley, Scott A.] Novartis Res Fdn, Prot Sci Dept, Genom Inst, San Diego, CA USA. [Astakhova, Tamara; Duan, Lian; Jaroszewski, Lukasz; Krishna, S. Sri; Morse, Andrew T.; Wooley, John; Godzik, Adam] Univ Calif San Diego, Ctr Res Biol Syst, La Jolla, CA 92093 USA. EM wilson@scripps.edu RI Godzik, Adam/A-7279-2009 OI Godzik, Adam/0000-0002-2425-852X FU National Institutes of General Medical Sciences Protein Structure Initiative [P50 GM62411, U54 GM074898]; Department of Energy, Office of Biological and Environmental Research; National Institutes of Health; National Institutes of Health (National Center for Research Resources); National Institutes of Health (National Institute of General Medical Sciences) FX This work was supported by National Institutes of General Medical Sciences Protein Structure Initiative grant Nos. P50 GM62411 and U54 GM074898. Portions of this research were carried out at the Stanford Synchrotron Radiation Lightsource (SSRL). The SSRL is a national user facility operated by Stanford University on behalf of the US Department of Energy, Office of Basic Energy Sciences. The SSRL Structural Molecular Biology Program is supported by the Department of Energy, Office of Biological and Environmental Research and by the National Institutes of Health (National Center for Research Resources, Biomedical Technology Program and the National Institute of General Medical Sciences). D. hafniense DCB-2 was a gift from Drs Tamara Cole and Jim Tiedje, Michigan State University, East Lansing, Michigan, USA. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of General Medical Sciences or the National Institutes of Health. NR 42 TC 0 Z9 0 U1 0 U2 6 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1744-3091 J9 ACTA CRYSTALLOGR F JI Acta Crystallogr. F-Struct. Biol. Cryst. Commun. PD OCT PY 2010 VL 66 BP 1167 EP 1173 DI 10.1107/S1744309110007517 PN 10 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA 658QA UT WOS:000282503300006 PM 20944207 ER PT J AU Koonin, EV AF Koonin, Eugene V. TI New variants of known folds: do they bring new biology? SO ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY AND CRYSTALLIZATION COMMUNICATIONS LA English DT Article ID STRUCTURAL GENOMICS; FAMILY; PROTEINS; EVOLUTION; DATABASE; DOMAINS; YEAZ AB New distinct versions of known protein folds provide a powerful means of protein-function prediction that complements sequence and genomic context analysis. These structures do not supplant direct biochemical experiments, but are indispensable for the complete characterization of proteins. C1 NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Koonin, EV (reprint author), NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. EM koonin@ncbi.nlm.nih.gov NR 26 TC 2 Z9 2 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1744-3091 J9 ACTA CRYSTALLOGR F JI Acta Crystallogr. F-Struct. Biol. Cryst. Commun. PD OCT PY 2010 VL 66 BP 1226 EP 1229 DI 10.1107/S1744309110013242 PN 10 PG 4 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA 658QA UT WOS:000282503300014 PM 20944215 ER PT J AU Hardy, R Cooper, R Shah, I Harridge, S Guralnik, J Kuh, D AF Hardy, Rebecca Cooper, Rachel Shah, Imran Harridge, Stephen Guralnik, Jack Kuh, Diana TI Is chair rise performance a useful measure of leg power? SO AGING CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Chair rises; leg extensor power; physical performance; standing balance ID MIDLIFE PHYSICAL PERFORMANCE; LOWER-EXTREMITY FUNCTION; FUNCTIONAL PERFORMANCE; OLDER-PEOPLE; BIRTH COHORT; STRENGTH; WOMEN; DISABILITY; MOBILITY; HEALTH AB Background and aims: Chair rise performance, which is simple to assess in a home or clinic setting, has been used as a method of predicting leg power deficit in older adults. More recently, chair rise performance has been assessed in younger populations as a baseline for assessment of subsequent age-related declines in function and power. However, as rising from a chair repeatedly not only requires lower limb strength and power but also good balance and coordination, it may not be purely a measure of leg power especially among these younger, well functioning groups who are yet to experience age-related declines and deficits in function. The aim of this study was to assess whether chair rise performance can be considered as a predictor of leg power, and hence of deficits in this, in men and women in mid-life. We assessed the relationship of chair rise performance with leg extensor power (LEP), measured using the Nottingham Power Rig (NPR), and with standing balance performance. Methods: LEP was measured in a clinic setting in a sub-sample of 81 men and 93 women from the MRC National Survey of Health and Development, a nationally representative cohort born in Britain in 1946. The time taken to rise from a chair 10 times and standing balance time were assessed during home visits at the same age. Results: Increasing LEP was associated with better chair rise performance among those who completed 10 chair rises in >= 15 seconds, after adjustment for body size (p=0.008). Better standing balance performance was associated with better chair rise performance in men, but not women. Conclusions: That LEP and standing balance are both related to chair rise time in men suggests that chair rise time should not be thought of purely as a proxy measure of leg power in middle-aged populations. This has implications for longitudinal studies which want to study age-related decline in chair rise performance. (Aging Clin Exp Res 2010; 22: 412-418) (C) 2010, Editrice Kurtis C1 [Hardy, Rebecca; Cooper, Rachel; Shah, Imran; Kuh, Diana] UCL, Div Populat Hlth, MRC, Unit Lifelong Hlth & Ageing, London WC1B 5JU, England. [Harridge, Stephen] Kings Coll London, Div Appl Biomed Res, London WC2R 2LS, England. [Guralnik, Jack] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. RP Hardy, R (reprint author), UCL, Div Populat Hlth, MRC, Unit Lifelong Hlth & Ageing, 33 Bedford Pl, London WC1B 5JU, England. EM r.hardy@nshd.mrc.ac.uk OI Harridge, Stephen/0000-0002-8203-0769; Cooper, Rachel/0000-0003-3370-5720 FU UK Medical Research Council; NIH, National Institute on Aging FX This research was supported by the UK Medical Research Council and in part by the Intramural Research Program of the NIH, National Institute on Aging. NR 19 TC 9 Z9 9 U1 3 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1594-0667 EI 1720-8319 J9 AGING CLIN EXP RES JI Aging Clin. Exp. Res. PD OCT-DEC PY 2010 VL 22 IS 5-6 BP 412 EP 418 PG 7 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 751IX UT WOS:000289611800009 PM 21422795 ER PT J AU Lauretani, F Ceda, GP Maggio, M Nardelli, A Saccavini, M Ferrucci, L AF Lauretani, Fulvio Ceda, Gian Paolo Maggio, Marcello Nardelli, Anna Saccavini, Marsilio Ferrucci, Luigi TI Capturing side-effect of medication to identify persons at risk of delirium SO AGING CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Cause and prevention; cholinergic deficiency; delirium ID ANTICHOLINERGIC PROPERTIES; ALZHEIMERS-DISEASE; HYPOTHESIS; DEMENTIA; DRUGS AB Delirium, an acute confusional state characterized by decline in attention and cognition, is a common, life-threatening, but potentially preventable clinical syndrome among older persons. Deficits in cholinergic function have been postulated to cause delirium and cognitive decline. In particular, an imbalance between levels of acetylcholine and monoamine (such as dopamine) may cause delirium. We describe two cases of delirium in hospitalized older patients, supporting the "cholinergic deficiency hypothesis". In the first patient, hypo-reactive delirium developed a few hours after a dose of the long-acting opiate tramadol (a drug with anticholinergic effect) as analgesic for pain related to advanced peripheral artery disease. In the second patient, with vascular parkinsonism plus pre-frontal cortex vascular lesions, hyper-reactive delirium developed a few hours after a prescribed administration of L-dopa. These symptoms disappeared completely on the following day. These two "natural" experiments support the hypothesis that both hypo-reactive and hyper-active delirium may be caused by a reduction in cholinergic signaling. (Aging Clin Exp Res 2010; 22: 456-458) (C) 2010, Editrice Kurtis C1 [Ferrucci, Luigi] NIA, Longitudinal Studies Sect, NIH, Baltimore, MD 21224 USA. RP Lauretani, F (reprint author), Univ Hosp Parma, Dept Geriatr & Rehabil, Lab Movement Anal, Geriatr Unit, Via Gramsci 14, I-43100 Parma, Italy. EM flauretani@ao.pr.it RI Lauretani, Fulvio/K-5115-2016; OI Lauretani, Fulvio/0000-0002-5287-9972; Ceda, Gian Paolo/0000-0002-9648-8295 NR 11 TC 9 Z9 9 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1594-0667 EI 1720-8319 J9 AGING CLIN EXP RES JI Aging Clin. Exp. Res. PD OCT-DEC PY 2010 VL 22 IS 5-6 BP 456 EP 458 PG 3 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 751IX UT WOS:000289611800015 PM 21422797 ER PT J AU El-Bassel, N Wingood, G Wyatt, GE Jemmott, JB Pequegnat, W Landis, JR Gilbert, L Remien, RH Witte, S Wu, E DiClemente, R Myers, H Jemmott, LS Metzger, D Brown, T Greene, Q Helker, C Robinson, N Allen-Taylor, L Appleby, D Crowley, E Ashton, D Goddard, DA Daniel, T Henderson, T Rivkin, I Green, CM Brently, J Cheraquit, RD Gray, D Hakim, L Sarfo, B Saunders, K Simmons, D Wilson, K Braxton, ND Camp, C Conner, A Gibson, J Harmon, A Latham, T Pennick-Walters, T Rucker, K Steinback, S Williams, P Williams, R Williams, S Chancy, K Levels, F Thomas, N Bennett, R Bryson, S Curtis, S Jones, M Jones, P Moore, M Patterson, C Penn, M Samuel, A Shine, R Stevenson, R Tate, R Taylor, M Wroton, C Johnson, P Matthews, L Mendoza, R Winkle, A Daugherty, J Er, D Felix, L Hailemeskal, M Howard, T Hoyte, T Smith, J Smith, L DeMorst, L Regan, R Rogers, E Carter, K Collier, C Croom, M Samuel, D Sosa, J Taylor, B Bryan, TS Robinson-Simpson, L Camp, C Loeb, T Williams, J Gueits, L Bayer, C Caliendo, A Freeman, S Ingersoll, J Maslankowski, L McGee-Smith, D Moorer, P Mott, M Woodard, B Bannerman, C Blake, W Bratts, T Copeland, O De Jesus-Sosa, D Faly, A Hailemeskal, M Hoyte, T Hsu, J Irobunda, H Johnson, S Napoleon, F Williams, K Combs, S MacDonald, M Roy, L White, D Woods, P Wyatt, C AF El-Bassel, Nabila Wingood, Gina Wyatt, Gail E. Jemmott, John B., III Pequegnat, Willo Landis, J. Richard Gilbert, Louisa Remien, Robert H. Witte, Susan Wu, Elwin DiClemente, Ralph Myers, Hector Jemmott, Loretta Sweet Metzger, David Brown, Trina Greene, Quincy Helker, Christopher Robinson, Nancy Allen-Taylor, Lynne Appleby, Dina Crowley, Evelyn Ashton, Deidre Goddard, Dawn A. Daniel, Tamu Henderson, Tina Rivkin, Inna Green, Cynthia M. Brently, Jeffery Cheraquit, Rebecca D. Gray, Deborah Hakim, Linda Sarfo, Bright Saunders, Kijana Simmons, Dawn Wilson, Keisha Braxton, Nikia D. Camp, Christina Conner, Anita Gibson, Jevon Harmon, Alvin Latham, Teaniese Pennick-Walters, Tiffany Rucker, Kenneth Steinback, Shammara Williams, Phillip Williams, Richard Williams, Shauni Chancy, Kevin Levels, Frank Thomas, Nathaniel Bennett, Reginald Bryson, Shirley Curtis, Salema Jones, Michelle Jones, Phyllis Moore, Malachi Patterson, Charles Penn, Marcia Samuel, Alicia Shine, Randy Stevenson, Ralph Tate, Robert Taylor, Michael Wroton, Charlotte Johnson, Pearl Matthews, Lisa Mendoza, Rhonda Winkle, Allan Daugherty, Jill Er, Deja Felix, Linda Hailemeskal, Meklit Howard, Toya Hoyte, Tamika Smith, Jamie Smith, Lisa DeMorst, Les Regan, Rotrease Rogers, Elsa Carter, Karen Collier, Calvin Croom, Mikia Samuel, Dionna Sosa, Joseph Taylor, Brian Bryan, Tamara S. Robinson-Simpson, LaShun Camp, Christina Loeb, Tamra Williams, John Gueits, Lynette Bayer, Cynthia Caliendo, Angela Freeman, Shalonda Ingersoll, Jessica Maslankowski, Lisa McGee-Smith, Debra Moorer, Patrice Mott, Michelle Woodard, Bennie Bannerman, Claudette Blake, Warren Bratts, Tiffany Copeland, Olivia De Jesus-Sosa, Daisy Faly, Adefunke Hailemeskal, Meklit Hoyte, Tamika Hsu, Janet Irobunda, Heather Johnson, Shakaria Napoleon, Frandy Williams, Karen Combs, Sonya MacDonald, Mathew Roy, Lolita White, Dalena Woods, Pandora Wyatt, Crystal CA NIMH Multisite HIV STD Prevention Steering Committee Co-Investigators Scarlett Bellamy Data Coordinating Ctr Project Directors Angela Ankoma Facilitators Jeffery Brently TI Concordant and Discordant Reports on Shared Sexual Behaviors and Condom Use Among African American Serodiscordant Couples in Four Cities SO AIDS AND BEHAVIOR LA English DT Article DE HIV; Serodiscordant; Concordance; Discordance; African American couples ID HETEROSEXUAL COUPLES; RELIABILITY; HISTORIES; PARTNERS; SATISFACTION; AGREEMENT AB This paper examines the concordance of reported shared sexual behaviors, including condom use, among 535 heterosexual, African American, serodiscordant couples and identifies factors that might predict discordant reports. Percentages of agreement, Kappa and McNemar's statistics and conditional probability indices are used to measure concordance. Logistic regression models identify predictors of couples' discordant sexual reports. Analyses revealed Kappa statistics for reporting anal sex, fellatio and cunnilingus indicated moderate to substantial agreement. The effects of demographics and the couples' relationship contexts on concordance of reported sexual behaviors were found to vary somewhat by gender and type of sexual behavior. Findings showed that concordance of reporting between the couples was consistent for the past 90 and 30 days. Findings from this paper provide new scientific insights into the knowledge base of self-reported couples' data and suggest that these data can be used to evaluate their accuracy and serve as a proxy for validity. C1 [Wyatt, Gail E.; Henderson, Tina; Rivkin, Inna; Chancy, Kevin; Levels, Frank; Thomas, Nathaniel; DeMorst, Les; Regan, Rotrease; Bryan, Tamara S.; Williams, John; McGee-Smith, Debra; De Jesus-Sosa, Daisy; Williams, Karen] Univ Calif Los Angeles, Los Angeles, CA 90024 USA. [Pequegnat, Willo] NIMH, Bethesda, MD 20892 USA. RI Metzger, David/D-9499-2012 NR 25 TC 8 Z9 8 U1 0 U2 4 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1090-7165 EI 1573-3254 J9 AIDS BEHAV JI AIDS Behav. PD OCT PY 2010 VL 14 IS 5 BP 1011 EP 1022 DI 10.1007/s10461-010-9699-7 PG 12 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 654KU UT WOS:000282168000004 ER PT J AU Wingood, G El-Bassel, N Wingood, G Wyatt, GE Jemmott, JB Pequegnat, W Landis, JR Bellamy, S Gilbert, L Remien, RH Witte, S Wu, E DiClemente, R Myers, H Jemmott, LS Metzger, D Brown, T Greene, Q Helker, C Robinson, N Allen-Taylor, L Appleby, D Crowley, E Ashton, D Goddard, DA Daniel, T Henderson, T Rivkin, I Green, CM Brently, J Cheraquit, RD Gray, D Hakim, L Sarfo, B Saunders, K Simmons, D Wilson, K Braxton, ND Camp, C Conner, A Gibson, J Harmon, A Latham, T Pennick-Walters, T Rucker, K Steinback, S Williams, P Williams, R Williams, S Chancy, K Levels, F Thomas, N Bennett, R Bryson, S Curtis, S Jones, M Jones, P Moore, M Patterson, C Penn, M Samuel, A Shine, R Stevenson, R Tate, R Taylor, M Wroton, C Griffith, D Johnson, P Matthews, L Mendoza, R Winkle, A Daugherty, J Er, D Felix, L Hailemeskal, M Howard, T Hoyte, T Smith, J Smith, L DeMorst, L Regan, R Rogers, E Carter, K Collier, C Croom, M Samuel, D Sosa, J Taylor, B Bryan, TS Robinson-Simpson, L Camp, C Loeb, T Williams, J Gueits, L Bayer, C Caliendo, A Freeman, S Ingersoll, J Maslankowski, L McGee-Smith, D Moorer, P Mott, M Woodard, B Bannerman, C Blake, W Bratts, T Copeland, O De Jesus-Sosa, D Faly, A Hailemeskal, M Hoyte, T Hsu, J Irobunda, H Johnson, S Napoleon, F Williams, K Combs, S MacDonald, M Roy, L White, D Woods, P Wyatt, C AF Wingood, Gina El-Bassel, Nabila Wingood, Gina Wyatt, Gail E. Jemmott, John B., III Pequegnat, Willo Landis, J. Richard Bellamy, Scarlett Gilbert, Louisa Remien, Robert H. Witte, Susan Wu, Elwin DiClemente, Ralph Myers, Hector Jemmott, Loretta Sweet Metzger, David Brown, Trina Greene, Quincy Helker, Christopher Robinson, Nancy Allen-Taylor, Lynne Appleby, Dina Crowley, Evelyn Ashton, Deidre Goddard, Dawn A. Daniel, Tamu Henderson, Tina Rivkin, Inna Green, Cynthia M. Brently, Jeffery Cheraquit, Rebecca D. Gray, Deborah Hakim, Linda Sarfo, Bright Saunders, Kijana Simmons, Dawn Wilson, Keisha Braxton, Nikia D. Camp, Christina Conner, Anita Gibson, Jevon Harmon, Alvin Latham, Teaniese Pennick-Walters, Tiffany Rucker, Kenneth Steinback, Shammara Williams, Phillip Williams, Richard Williams, Shauni Chancy, Kevin Levels, Frank Thomas, Nathaniel Bennett, Reginald Bryson, Shirley Curtis, Salema Jones, Michelle Jones, Phyllis Moore, Malachi Patterson, Charles Penn, Marcia Samuel, Alicia Shine, Randy Stevenson, Ralph Tate, Robert Taylor, Michael Wroton, Charlotte Griffith, Derryck Johnson, Pearl Matthews, Lisa Mendoza, Rhonda Winkle, Allan Daugherty, Jill Er, Deja Felix, Linda Hailemeskal, Meklit Howard, Toya Hoyte, Tamika Smith, Jamie Smith, Lisa DeMorst, Les Regan, Rotrease Rogers, Elsa Carter, Karen Collier, Calvin Croom, Mikia Samuel, Dionna Sosa, Joseph Taylor, Brian Bryan, Tamara S. Robinson-Simpson, LaShun Camp, Christina Loeb, Tamra Williams, John Gueits, Lynette Bayer, Cynthia Caliendo, Angela Freeman, Shalonda Ingersoll, Jessica Maslankowski, Lisa McGee-Smith, Debra Moorer, Patrice Mott, Michelle Woodard, Bennie Bannerman, Claudette Blake, Warren Bratts, Tiffany Copeland, Olivia De Jesus-Sosa, Daisy Faly, Adefunke Hailemeskal, Meklit Hoyte, Tamika Hsu, Janet Irobunda, Heather Johnson, Shakaria Napoleon, Frandy Williams, Karen Combs, Sonya MacDonald, Mathew Roy, Lolita White, Dalena Woods, Pandora Wyatt, Crystal CA NIMH Multisite HIV STD Prevention TI Risky Sexual Behavior and Correlates of STD Prevalence Among African American HIV Serodiscordant Couples SO AIDS AND BEHAVIOR LA English DT Article DE HIV; Serodiscordant; African-American couples ID TRANSMITTED-DISEASES; TRICHOMONAS-VAGINALIS; UNITED-STATES; WOMEN; HEALTH; TRIAL; ADOLESCENTS; INFECTIONS; BELIEFS; AIDS AB This paper reports baseline behavioral and biological data collected from a cohort of 535 African American HIV serodiscordant couples enrolled in the Eban study across four urban metro areas. Data were collected on (1) the prevalence of risky sexual behaviors that occur within a couple and with concurrent sexual partners, (2) the STD prevalence for each member of the couple and (3) the correlates of STDs in the male partner as well as in the female partner. Presentation of the sociodemographic characterization and HIV risk behavior profiles of African American HIV serodiscordant couples represents an important initial description of a hidden, vulnerable population. Future research should be conducted with diverse samples of African American couples (i.e., younger couples, non-stable couples) to explore other potential correlates of STD prevalence. C1 [Wingood, Gina; Myers, Hector; Henderson, Tina; Rivkin, Inna; Chancy, Kevin; Levels, Frank; Thomas, Nathaniel; DeMorst, Les; Regan, Rotrease; Rogers, Elsa; Loeb, Tamra; Williams, John; McGee-Smith, Debra; De Jesus-Sosa, Daisy; Williams, Karen] Univ Calif Los Angeles, Los Angeles, CA 90024 USA. [Pequegnat, Willo] NIMH, Bethesda, MD 20892 USA. RI Metzger, David/D-9499-2012 NR 38 TC 6 Z9 6 U1 1 U2 7 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1090-7165 EI 1573-3254 J9 AIDS BEHAV JI AIDS Behav. PD OCT PY 2010 VL 14 IS 5 BP 1023 EP 1031 DI 10.1007/s10461-010-9698-8 PG 9 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 654KU UT WOS:000282168000005 ER PT J AU El-Bassel, N Wingood, G Wyatt, GE Jemmott, JB Pequegnat, W Landis, JR Bellamy, S Gilbert, L Remien, RH Witte, S Wu, E DiClemente, R Myers, H Jemmott, LS Metzger, D Brown, T Greene, Q Helker, C Robinson, N Allen-Taylor, L Appleby, D Crowley, E Ankoma, A Ashton, D Goddard, DA Daniel, T Henderson, T Rivkin, I Green, CM Brently, J Cheraquit, RD Gray, D Hakim, L Sarfo, B Saunders, K Simmons, D Wilson, K Braxton, ND Camp, C Conner, A Gibson, J Harmon, A Latham, T Pennick-Walters, T Rucker, K Steinback, S Williams, P Williams, R Williams, S Chancy, K Levels, F Thomas, N Bennett, R Bryson, S Curtis, S Jones, M Jones, P Moore, M Patterson, C Penn, M Samuel, A Shine, R Stevenson, R Tate, R Taylor, M Wroton, C Griffith, D Johnson, P Matthews, L Mendoza, R Winkle, A Daugherty, J Er, D Felix, L Hailemeskal, M Howard, T Hoyte, T Smith, J Smith, L DeMorst, L Regan, R Rogers, E Carter, K Collier, C Croom, M Samuel, D Sosa, J Taylor, B Tamara Robinson-Simpson, L Camp, C Loeb, T Williams, J Gueits, L Bayer, C Caliendo, A Freeman, S Ingersoll, J Maslankowski, L McGee-Smith, D Moorer, P Mott, M Woodard, B Bannerman, C Blake, W Bratts, T Copeland, O De Jesus-Sosa, D Faly, A Hailemeskal, M Hoyte, T Hsu, J Irobunda, H Johnson, S Napoleon, F Williams, K Combs, S MacDonald, M Roy, L White, D Woods, P Wyatt, C AF El-Bassel, Nabila Wingood, Gina Wyatt, Gail E. Jemmott, John B., III Pequegnat, Willo Landis, J. Richard Bellamy, Scarlett Gilbert, Louisa Remien, Robert H. Witte, Susan Wu, Elwin DiClemente, Ralph Myers, Hector Jemmott, Loretta Sweet Metzger, David Brown, Trina Greene, Quincy Helker, Christopher Robinson, Nancy Allen-Taylor, Lynne Appleby, Dina Crowley, Evelyn Ankoma, Angela Ashton, Deidre Goddard, Dawn A. Daniel, Tamu Henderson, Tina Rivkin, Inna Green, Cynthia M. Brently, Jeffery Cheraquit, Rebecca D. Gray, Deborah Hakim, Linda Sarfo, Bright Saunders, Kijana Simmons, Dawn Wilson, Keisha Braxton, Nikia D. Camp, Christina Conner, Anita Gibson, Jevon Harmon, Alvin Latham, Teaniese Pennick-Walters, Tiffany Rucker, Kenneth Steinback, Shammara Williams, Phillip Williams, Richard Williams, Shauni Chancy, Kevin Levels, Frank Thomas, Nathaniel Bennett, Reginald Bryson, Shirley Curtis, Salema Jones, Michelle Jones, Phyllis Moore, Malachi Patterson, Charles Penn, Marcia Samuel, Alicia Shine, Randy Stevenson, Ralph Tate, Robert Taylor, Michael Wroton, Charlotte Griffith, Derryck Johnson, Pearl Matthews, Lisa Mendoza, Rhonda Winkle, Allan Daugherty, Jill Er, Deja Felix, Linda Hailemeskal, Meklit Howard, Toya Hoyte, Tamika Smith, Jamie Smith, Lisa DeMorst, Les Regan, Rotrease Rogers, Elsa Carter, Karen Collier, Calvin Croom, Mikia Samuel, Dionna Sosa, Joseph Taylor, Brian Tamara Robinson-Simpson, LaShun Camp, Christina Loeb, Tamra Williams, John Gueits, Lynette Bayer, Cynthia Caliendo, Angela Freeman, Shalonda Ingersoll, Jessica Maslankowski, Lisa McGee-Smith, Debra Moorer, Patrice Mott, Michelle Woodard, Bennie Bannerman, Claudette Blake, Warren Bratts, Tiffany Copeland, Olivia De Jesus-Sosa, Daisy Faly, Adefunke Hailemeskal, Meklit Hoyte, Tamika Hsu, Janet Irobunda, Heather Johnson, Shakaria Napoleon, Frandy Williams, Karen Combs, Sonya MacDonald, Mathew Roy, Lolita White, Dalena Woods, Pandora Wyatt, Crystal CA NIMH Multisite HIV STD Prevention TI The Contribution of Male and Female Partners' Substance Use to Sexual Risks and STDs Among African American HIV Serodiscordant Couples SO AIDS AND BEHAVIOR LA English DT Article DE HIV; Serodiscordant; Substance use; STDs; African-American couples ID INJECTION-DRUG USERS; ALCOHOL-CONSUMPTION; YOUNG-ADULTS; CONDOM USE; INFECTION; WOMEN; BEHAVIOR; PREVALENCE; SMOKERS; YOUTH AB Growing evidence suggests that drug and alcohol use are fueling the heterosexual transmission of HIV among African Americans. This study aims to examine the relative contribution of drug and alcohol use of male and female partners to risks of heterosexual transmission of HIV among 535 African American HIV serodiscordant couples (N = 1,070 participants) who participated in an HIV prevention trial. Associations found between use of drugs and alcohol by one or both partners and sexual risk indicators varied by type of substance and whether male or female partner or both partners reported use. The findings suggest multiple ways in which substance use of male and female partners may be contributing to the heterosexual transmission of HIV and other STDs among African Americans and underscore the need for HIV prevention strategies to address dyadic patterns of substance use that lead to sexual risks. C1 [Wyatt, Gail E.; Myers, Hector; Henderson, Tina; Rivkin, Inna; Chancy, Kevin; Levels, Frank; Thomas, Nathaniel; DeMorst, Les; Regan, Rotrease; Rogers, Elsa; Loeb, Tamra; Williams, John; McGee-Smith, Debra; De Jesus-Sosa, Daisy; Williams, Karen] Univ Calif Los Angeles, Los Angeles, CA 90024 USA. [Pequegnat, Willo] NIMH, Bethesda, MD 20892 USA. RI Metzger, David/D-9499-2012 NR 25 TC 8 Z9 8 U1 1 U2 7 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1090-7165 J9 AIDS BEHAV JI AIDS behav. PD OCT PY 2010 VL 14 IS 5 BP 1045 EP 1054 DI 10.1007/s10461-010-9695-y PG 10 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 654KU UT WOS:000282168000007 ER PT J AU Conroy, SA Laeyendecker, O Redd, AD Collinson-Streng, A Kong, XR Makumbi, F Lutalo, T Sewankambo, N Kiwanuka, N Gray, RH Wawer, MJ Serwadda, D Quinn, TC AF Conroy, Samantha A. Laeyendecker, Oliver Redd, Andrew D. Collinson-Streng, Aleisha Kong, Xiangrong Makumbi, Fredrick Lutalo, Tom Sewankambo, Nelson Kiwanuka, Noah Gray, Ronald H. Wawer, Maria J. Serwadda, David Quinn, Thomas C. CA Rakai Hlth Sci Program TI Changes in the Distribution of HIV Type 1 Subtypes D and A in Rakai District, Uganda Between 1994 and 2002 SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID DISEASE PROGRESSION; INFECTION; RECOMBINANTS; TANZANIA; DIVERSITY; VARIANTS; EPIDEMIC; KINSHASA; CONGO AB HIV-1 subtype D (HIV-1D) progresses to disease faster and has lower transmissibility than subtype A (HIV-1A). We examined whether these differences could lead to a population level change in the distribution of these subtypes over time. HIV-1 viral RNA was extracted from stored serum samples from HIV-positive subjects participating in a population-based cohort study in Rakai, Uganda in 1994 and 2002. Portions of the viral proteins gag and gp41 were sequenced and subtyped. HIV-1 subtype assignments were generated for 773 subjects in 1994 and 812 subjects in 2002. The change in subtype distribution of the population as a whole as well as quartile age groups were examined for significant changes using a linear model. There was a significant decrease in the proportion of subjects infected with HIV-1D from 70.2% to 62.4% and a significant increase in subjects infected with HIV-1A from 16.7% to 23.3% over the 8-year period (p = 0.005). The most marked changes in proportion of HIV-1D and A were seen in the younger individuals (<25 and 25-30 years; p < 0.05). The percentages of subjects infected with HIV-1C and recombinant subtypes did not change significantly. Over this 8-year period, the overall viral population in this region evolved toward the less virulent HIV-1A strain, most likely as a consequence of the faster disease progression and lower transmissibility of HIV-1D. C1 [Laeyendecker, Oliver; Quinn, Thomas C.] Johns Hopkins Univ, Sch Med, Baltimore, MD 21205 USA. [Conroy, Samantha A.; Laeyendecker, Oliver; Redd, Andrew D.; Collinson-Streng, Aleisha; Quinn, Thomas C.] NIAID, Immunoregulat Lab, Div Intramural Res, NIH, Baltimore, MD USA. [Kong, Xiangrong; Gray, Ronald H.; Wawer, Maria J.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA. [Makumbi, Fredrick; Lutalo, Tom; Kiwanuka, Noah] Rakai Hlth Sci Program, Rakai, Uganda. [Sewankambo, Nelson] Makerere Univ, Sch Med, Kampala, Uganda. [Kiwanuka, Noah; Serwadda, David] Makerere Univ, Sch Publ Hlth, Kampala, Uganda. RP Quinn, TC (reprint author), Johns Hopkins Univ, Sch Med, Rangos Bldg,Room 530,855 N Wolfe St, Baltimore, MD 21205 USA. EM tquinn2@jhmi.edu RI Laeyendecker, Oliver/B-9331-2009; OI Sewankambo, Nelson/0000-0001-9362-053X; Laeyendecker, Oliver/0000-0002-6429-4760 FU Division of Intramural Research, NIAID, NIH; NIAID [R01 A134826, R01 A134265]; NICHD [5P30HD06826]; World Bank STI Project, Uganda; Henry M. Jackson Foundation; Fogarty Foundation [5D43TW00010]; Bill and Melinda Gates Institute for Population and Reproductive Health [HM114622-HM115320, HM115321-HM115893] FX The authors would like to thank all the participants of the Rakai cohort and the staff of the Rakai health science program. We would also like to thank Susanna Lamers for her technical expertise. This study was supported in part by funding from the Division of Intramural Research, NIAID, NIH; NIAID Grants R01 A134826 and R01 A134265); NICHD (Grant 5P30HD06826); the World Bank STI Project, Uganda; the Henry M. Jackson Foundation; the Fogarty Foundation (Grant 5D43TW00010); and the Bill and Melinda Gates Institute for Population and Reproductive Health at J. H. U. All sequence data have been submitted to GenBank (ascension numbers for the gp41 sequences: HM114622-HM115320 and for the p24 sequences: HM115321-HM115893). NR 24 TC 22 Z9 22 U1 1 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2010 VL 26 IS 10 BP 1087 EP 1091 DI 10.1089/aid.2010.0054 PG 5 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 665OC UT WOS:000283044200438 PM 20925575 ER PT J AU Aboud, S Bakari, M Francis, J Buma, D Moshiro, C Aris, EA Lyamuya, EF Janabi, M Godoy-Ramirez, K Earl, P Robb, M Marovich, M Michael, N Wahren, B Pallangyo, K Biberfeld, G Mhalu, F Sandstrom, E AF Aboud, S. Bakari, M. Francis, J. Buma, D. Moshiro, C. Aris, E. A. Lyamuya, E. F. Janabi, M. Godoy-Ramirez, K. Earl, P. Robb, M. Marovich, M. Michael, N. Wahren, B. Pallangyo, K. Biberfeld, G. Mhalu, F. Sandstrom, E. TI Broad and strong immune responses in a trial of a heterologous DNA prime MVA boost HIV vaccine among healthy Tanzanian volunteers SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT AIDS Vaccine 2010 CY SEP 28-OCT 01, 2010 CL Atlanta, GA C1 [Aboud, S.; Bakari, M.; Moshiro, C.; Lyamuya, E. F.; Pallangyo, K.; Mhalu, F.] Muhimbili Univ Hlth & Allied Sci, Dar Es Salaam, Tanzania. [Francis, J.] Natl Inst Med Res, Dar Es Salaam, Tanzania. [Buma, D.; Aris, E. A.; Janabi, M.] Muhimbili Natl Hosp, Dar Es Salaam, Tanzania. [Godoy-Ramirez, K.] Swedish Inst Infect Dis Control SMI, Solna, Sweden. [Earl, P.] NIAID, NIH, Bethesda, MD 20892 USA. [Robb, M.; Marovich, M.; Michael, N.] Walter Reed Army Inst Res, Rockville, MD USA. [Wahren, B.; Biberfeld, G.] Karolinska Inst, Swedish Inst Infect Dis Control, Stockholm, Sweden. [Sandstrom, E.] Karolinska Inst Sodersjukhuset, Stockholm, Sweden. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2010 VL 26 IS 10 BP A10 EP A10 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 665OC UT WOS:000283044200023 ER PT J AU Alexandre, KB Gray, ES Moore, PL Pantophlet, R Chikwamba, R McMahon, J O'Keefe, B Morris, L AF Alexandre, K. B. Gray, E. S. Moore, P. L. Pantophlet, R. Chikwamba, R. McMahon, J. O'Keefe, B. Morris, L. TI Binding of the mannose-specific lectin, Griffithsin, to HIV-1 gp120 exposes the CD4-binding site SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT AIDS Vaccine 2010 CY SEP 28-OCT 01, 2010 CL Atlanta, GA C1 [Alexandre, K. B.; Gray, E. S.; Moore, P. L.; Morris, L.] Natl Inst Communicable Dis, Johannesburg, Gauteng, South Africa. [Pantophlet, R.] Simon Fraser Univ, Fac Hlth Sci, Vancouver, BC, Canada. [Chikwamba, R.] Ctr Sci & Ind Res, Pretoria, Gauteng, South Africa. [McMahon, J.; O'Keefe, B.] NCI, Ctr Canc Res, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2010 VL 26 IS 10 BP A124 EP A124 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 665OC UT WOS:000283044200317 ER PT J AU Amara, R Kwa, S Lai, L Siddiqui, M Wyatt, L Kozlowski, P Montefiori, D Hirsch, V Moss, B Robinson, H AF Amara, R. Kwa, S. Lai, L. Siddiqui, M. Wyatt, L. Kozlowski, P. Montefiori, D. Hirsch, V. Moss, B. Robinson, H. TI CD40L expressed on virus-like particles adjuvants prevention of acquisition mediated by a DNA/MVA vaccine SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT AIDS Vaccine 2010 CY SEP 28-OCT 01, 2010 CL Atlanta, GA C1 [Amara, R.; Kwa, S.; Lai, L.; Siddiqui, M.; Wyatt, L.; Robinson, H.] Emory Univ, Atlanta, GA 30322 USA. [Kozlowski, P.] Louisiana State Univ, New Orleans, LA USA. [Montefiori, D.] Duke Univ, Med Ctr, Durham, NC USA. [Hirsch, V.; Moss, B.] NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2010 VL 26 IS 10 BP A16 EP A16 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 665OC UT WOS:000283044200037 ER PT J AU Bar, KJ Decker, JM Ganusov, VV Li, H McLellan, JS Yang, Y Pavlicek, JW Keele, BF Gao, F Perelson, AS Kwong, PD Hahn, BH Shaw, GM AF Bar, K. J. Decker, J. M. Ganusov, V. V. Li, H. McLellan, J. S. Yang, Y. Pavlicek, J. W. Keele, B. F. Gao, F. Perelson, A. S. Kwong, P. D. Hahn, B. H. Shaw, G. M. TI Molecular targets and potency of HIV-1 neutralization revealed by dynamic assessment of transmitted/founder virus antibody recognition and escape SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT AIDS Vaccine 2010 CY SEP 28-OCT 01, 2010 CL Atlanta, GA C1 [Bar, K. J.; Decker, J. M.; Li, H.; Hahn, B. H.; Shaw, G. M.] Univ Alabama, Birmingham, AL USA. [Ganusov, V. V.] Univ Tennessee, Knoxville, TN USA. [McLellan, J. S.; Yang, Y.; Kwong, P. D.] NIAID, NIH, Bethesda, MD 20892 USA. [Pavlicek, J. W.; Gao, F.] Duke Univ, Med Ctr, Durham, NC USA. [Keele, B. F.] SAIC Frederick, Frederick, MD USA. [Perelson, A. S.] Los Alamos Natl Lab, Los Alamos, NM USA. RI McLellan, Jason/A-6874-2010 NR 0 TC 1 Z9 1 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2010 VL 26 IS 10 BP A11 EP A12 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 665OC UT WOS:000283044200026 ER PT J AU Bonsignori, M Hwang, K Chen, X Tsao, C Bilska, M Fang, W Marshall, D Whitesides, JF Crump, JA Sam, N Saidi, K Kepler, TB Wu, X Mascola, JR Nabel, GJ Pancera, M Zhu, J Kwong, PD Sodroski, J Lavine, C Yang, X Feng, G Montefiori, DC Liao, H Haynes, BF AF Bonsignori, M. Hwang, K. Chen, X. Tsao, C. Bilska, M. Fang, W. Marshall, D. Whitesides, J. F. Crump, J. A. Sam, N. Saidi, K. Kepler, T. B. Wu, X. Mascola, J. R. Nabel, G. J. Pancera, M. Zhu, J. Kwong, P. D. Sodroski, J. Lavine, C. Yang, X. Feng, G. Montefiori, D. C. Liao, H. Haynes, B. F. TI Immunoregulation of HIV-1 broadly neutralizing antibody responses: deciphering maturation paths for antibody induction SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT AIDS Vaccine 2010 CY SEP 28-OCT 01, 2010 CL Atlanta, GA C1 [Bonsignori, M.; Hwang, K.; Chen, X.; Tsao, C.; Marshall, D.; Whitesides, J. F.; Feng, G.; Liao, H.; Haynes, B. F.] Duke Univ, Med Ctr, Duke Human Vaccine Inst, Durham, NC USA. [Bilska, M.; Fang, W.; Montefiori, D. C.] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. [Crump, J. A.; Sam, N.] Kilimanjaro Christian Med Ctr, Moshi, Tanzania. [Saidi, K.] Harvard Univ, Sch Publ Hlth, Dept Populat & Int Hlth, Boston, MA 02115 USA. [Kepler, T. B.] Duke Univ, Med Ctr, Ctr Computat Immunol, Durham, NC USA. [Wu, X.; Mascola, J. R.; Nabel, G. J.; Pancera, M.; Zhu, J.; Kwong, P. D.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Sodroski, J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Lavine, C.; Yang, X.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. RI Bonsignori, Mattia/C-6745-2008 NR 0 TC 1 Z9 1 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2010 VL 26 IS 10 BP A153 EP A153 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 665OC UT WOS:000283044200391 ER PT J AU Bosinger, SE Klatt, NR Silvestri, G AF Bosinger, S. E. Klatt, N. R. Silvestri, G. TI Systems biology analysis of CD8-lymphocyte depletion in SIV-infected rhesus macaques SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT AIDS Vaccine 2010 CY SEP 28-OCT 01, 2010 CL Atlanta, GA C1 [Bosinger, S. E.; Silvestri, G.] Univ Penn Emory Univ, Philadelphia, PA USA. [Klatt, N. R.] NIAID, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2010 VL 26 IS 10 BP A114 EP A115 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 665OC UT WOS:000283044200291 ER PT J AU Brave, A Nilsson, C Biberfeld, G Earl, P Gudmundsdotter, L Hejdeman, B Marovich, M Michael, N Moss, B Petterson, S Polonis, V Robb, M Sandstrom, E Wahren, B AF Brave, A. Nilsson, C. Biberfeld, G. Earl, P. Gudmundsdotter, L. Hejdeman, B. Marovich, M. Michael, N. Moss, B. Petterson, S. Polonis, V. Robb, M. Sandstrom, E. Wahren, B. TI Vaccine-induced seropositivity (VISP) following immunization of healthy individuals with HIV DNA and recombinant modified vaccinia virus Ankara SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT AIDS Vaccine 2010 CY SEP 28-OCT 01, 2010 CL Atlanta, GA C1 [Brave, A.; Nilsson, C.; Biberfeld, G.; Gudmundsdotter, L.; Petterson, S.; Wahren, B.] Karolinska Inst, Solna, Sweden. [Brave, A.; Nilsson, C.; Biberfeld, G.; Gudmundsdotter, L.; Petterson, S.; Wahren, B.] Swedish Inst Infect Dis Control, Solna, Sweden. [Earl, P.; Moss, B.] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. [Hejdeman, B.; Sandstrom, E.] Stockholm S Hosp, Karolinska Inst, Stockholm, Sweden. [Marovich, M.; Michael, N.; Polonis, V.; Robb, M.] Walter Reed Army Inst Res, US Mil HIV Res Program, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2010 VL 26 IS 10 BP A11 EP A11 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 665OC UT WOS:000283044200024 ER PT J AU Brown, G Larkin, BD Little, S Johnson, D AF Brown, G. Larkin, B. D. Little, S. Johnson, D. TI Social, Behavioral, and Biological Factors experienced by Black and Hispanic Women that can Impact Participation in HIV Vaccine Trials Network Research SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT AIDS Vaccine 2010 CY SEP 28-OCT 01, 2010 CL Atlanta, GA C1 [Brown, G.] NIH, Bethesda, MD 20892 USA. [Larkin, B. D.] VRC, Washington, DC USA. [Little, S.] AED, Washington, DC USA. [Johnson, D.] VRC, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2010 VL 26 IS 10 BP A107 EP A108 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 665OC UT WOS:000283044200273 ER PT J AU Buonaguro, L Tornesello, M Marincola, FM Buonaguro, FM AF Buonaguro, L. Tornesello, M. Marincola, F. M. Buonaguro, F. M. TI Systems biology approach to predict immunogenicity of HIV vaccine SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT AIDS Vaccine 2010 CY SEP 28-OCT 01, 2010 CL Atlanta, GA C1 [Buonaguro, L.; Tornesello, M.; Buonaguro, F. M.] Ist Nazl Tumori, Naples, Italy. [Marincola, F. M.] NIH, Bethesda, MD 20892 USA. RI Tornesello, Maria Lina/A-1564-2009 OI Tornesello, Maria Lina/0000-0002-3523-3264 NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2010 VL 26 IS 10 BP A77 EP A78 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 665OC UT WOS:000283044200191 ER PT J AU Cheng, C Wang, L Gall, JG Nason, M Schwartz, RM Nabel, GJ AF Cheng, C. Wang, L. Gall, J. G. Nason, M. Schwartz, R. M. Nabel, G. J. TI The effect of Ad5 capsid- and fiber- specific neutralizing antibodies on vaccine-induced immunity and outcome in the STEP trial SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT AIDS Vaccine 2010 CY SEP 28-OCT 01, 2010 CL Atlanta, GA C1 [Cheng, C.; Wang, L.; Nason, M.; Schwartz, R. M.; Nabel, G. J.] NIH, VRC, Bethesda, MD 20892 USA. [Gall, J. G.] GenVec, Gaithersburg, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2010 VL 26 IS 10 BP A160 EP A160 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 665OC UT WOS:000283044200410 ER PT J AU Cofano, EB AF Cofano, E. Brocca TI Vaccination based on mucosal priming with replication-competent Adenovirus-SIV recombinants induces SIV-specific memory B cells in rhesus macaques SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT AIDS Vaccine 2010 CY SEP 28-OCT 01, 2010 CL Atlanta, GA C1 [Cofano, E. Brocca] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2010 VL 26 IS 10 BP A146 EP A146 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 665OC UT WOS:000283044200376 ER PT J AU Dai, K Wu, L Schmidt, SD Wu, X Shi, W Zhu, J Georgiev, I Boyington, JC Zhou, T Louder, MK McLellan, JS Kwong, PD Mascola, JR Yang, Z Nabel, J AF Dai, K. Wu, L. Schmidt, S. D. Wu, X. Shi, W. Zhu, J. Georgiev, I. Boyington, J. C. Zhou, T. Louder, M. K. McLellan, J. S. Kwong, P. D. Mascola, J. R. Yang, Z. Nabel, J. TI Elicitation of Neutralizing Antibodies Targeting to the CD4 Binding Site Using a Trimeric gp140 Immunogen SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT AIDS Vaccine 2010 CY SEP 28-OCT 01, 2010 CL Atlanta, GA C1 [Dai, K.; Wu, L.; Schmidt, S. D.; Wu, X.; Shi, W.; Zhu, J.; Georgiev, I.; Boyington, J. C.; Zhou, T.; Louder, M. K.; McLellan, J. S.; Kwong, P. D.; Mascola, J. R.; Yang, Z.; Nabel, J.] NIAID, VRC, NIH, Bethesda, MD 20892 USA. RI McLellan, Jason/A-6874-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2010 VL 26 IS 10 BP A159 EP A160 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 665OC UT WOS:000283044200409 ER PT J AU Dey, B Lagenaur, LA Villarroel, VA Bundoc, V Berger, E AF Dey, B. Lagenaur, L. A. Villarroel, V. A. Bundoc, V. Berger, E. TI A Bifunctional Designer Protein with Potential for HIV Prevention: Concepts and Implications SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT AIDS Vaccine 2010 CY SEP 28-OCT 01, 2010 CL Atlanta, GA C1 [Dey, B.; Lagenaur, L. A.; Villarroel, V. A.; Bundoc, V.; Berger, E.] NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2010 VL 26 IS 10 BP A97 EP A97 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 665OC UT WOS:000283044200244 ER PT J AU Duerr, A Huang, Y Moodie, Z Lawrence, D Robertson, M Buchbinder, S AF Duerr, A. Huang, Y. Moodie, Z. Lawrence, D. Robertson, M. Buchbinder, S. TI Analysis of the relative risk of HIV acquisition among Step study participants with extended follow-up SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT AIDS Vaccine 2010 CY SEP 28-OCT 01, 2010 CL Atlanta, GA C1 [Duerr, A.; Huang, Y.; Moodie, Z.] HIV Vaccine Trials Network, Seattle, WA USA. [Lawrence, D.] NIAID, Vaccine Clin Res Branch, VRP, DAIDS,NIH,DHHS, Bethesda, MD 20892 USA. [Robertson, M.] Merck & Co Inc, N Wales, PA USA. [Buchbinder, S.] San Francisco Dept Publ Hlth, HIV Res Sect, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2010 VL 26 IS 10 BP A9 EP A10 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 665OC UT WOS:000283044200021 ER PT J AU Fadda, L McVicar, D Carrington, M Altfeld, M AF Fadda, L. McVicar, D. Carrington, M. Altfeld, M. TI The role of HIV-1 peptide specificity in modulating KIR plus Natural Killer (NK) cell function SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT AIDS Vaccine 2010 CY SEP 28-OCT 01, 2010 CL Atlanta, GA C1 [Fadda, L.; Altfeld, M.] MIT & Harvard, MGH, Ragon Inst, Charlestown, MA USA. [McVicar, D.; Carrington, M.] NCI, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2010 VL 26 IS 10 BP A21 EP A21 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 665OC UT WOS:000283044200050 ER PT J AU Feng, Y Lybarger, E Mascola, J Wyatt, R AF Feng, Y. Lybarger, E. Mascola, J. Wyatt, R. TI Biophysical, antigenic and immunological analysis of HIV-1 Env constructs designed to focus the B cell response on conserved elements SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT AIDS Vaccine 2010 CY SEP 28-OCT 01, 2010 CL Atlanta, GA C1 [Feng, Y.; Wyatt, R.] IAVI, San Diego, CA USA. [Lybarger, E.; Mascola, J.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RI Feng, Yu/A-3396-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2010 VL 26 IS 10 BP A27 EP A27 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 665OC UT WOS:000283044200064 ER PT J AU Ferrari, G Korber, B Turnbull, E Liu, MK Goonetilleke, N Salazar, J Betts, M Gray, CM Roederer, M McMichael, A Weinhold, K AF Ferrari, G. Korber, B. Turnbull, E. Liu, M. K. Goonetilleke, N. Salazar, J. Betts, M. Gray, C. M. Roederer, M. McMichael, A. Weinhold, K. CA CHAVI 001 Team TI High magnitude and multifunctionality epitope-specific CD8+T-cell responses are associated are associated with selection of escape mutants in acute HIV infection SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT AIDS Vaccine 2010 CY SEP 28-OCT 01, 2010 CL Atlanta, GA C1 [Ferrari, G.; Weinhold, K.] Duke Univ, Med Ctr, Durham, NC USA. [Korber, B.] Los Alamos Natl Lab, Div Theoret, Los Alamos, NM USA. [Turnbull, E.] Univ Oxford, Jenner Inst, Compton, England. [Liu, M. K.; Goonetilleke, N.; McMichael, A.] Univ Oxford, Weatherall Inst Mol Med, Oxford, England. [Salazar, J.] Univ Alabama, Birmingham, AL USA. [Betts, M.] Univ Penn, Philadelphia, PA 19104 USA. [Gray, C. M.] Natl Inst Communicable Dis, Dept HIV Immunol, Johannesburg, South Africa. [Roederer, M.] NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2010 VL 26 IS 10 BP A5 EP A6 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 665OC UT WOS:000283044200011 ER PT J AU Ferrari, MG Pal, R Bowen, B Hudacik, L Thompson, D Lee, E Galmin, L Weiss, D Lewis, B Wyatt, L Earl, P Kalyanaraman, V Cristillo, A Markham, P VanCott, T AF Ferrari, M. G. Pal, R. Bowen, B. Hudacik, L. Thompson, D. Lee, E. Galmin, L. Weiss, D. Lewis, B. Wyatt, L. Earl, P. Kalyanaraman, V. Cristillo, A. Markham, P. VanCott, T. TI Efficacy of prime-boost vaccination via parental and mucosal routes against heterologous mucosal SHIV challenge SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT AIDS Vaccine 2010 CY SEP 28-OCT 01, 2010 CL Atlanta, GA C1 [Ferrari, M. G.; Pal, R.; Bowen, B.; Hudacik, L.; Thompson, D.; Lee, E.; Galmin, L.; Weiss, D.; Lewis, B.; Kalyanaraman, V.; Cristillo, A.; Markham, P.; VanCott, T.] Adv BioSci Labs, Kensington, MD USA. [Wyatt, L.; Earl, P.] NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2010 VL 26 IS 10 BP A165 EP A166 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 665OC UT WOS:000283044200424 ER PT J AU Finstad, S Zhang, G Jin, C Linde, C Hagan, E de la Rosa, M Zahn, R Wang, X Reimann, K Gaufin, T Apetrei, C Pandrea, I Miller, C McCune, J Picker, L Lifson, J Piatak, M Alter, G Veazey, R Barouch, D Hessell, A Burton, D Nimmerjahn, F Alam, M Haynes, B Gelman, R Brusic, V Letvin, N Schmitz, J AF Finstad, S. Zhang, G. Jin, C. Linde, C. Hagan, E. de la Rosa, M. Zahn, R. Wang, X. Reimann, K. Gaufin, T. Apetrei, C. Pandrea, I. Miller, C. McCune, J. Picker, L. Lifson, J. Piatak, M. Alter, G. Veazey, R. Barouch, D. Hessell, A. Burton, D. Nimmerjahn, F. Alam, M. Haynes, B. Gelman, R. Brusic, V. Letvin, N. Schmitz, J. TI Effect of Fc gamma-receptor polymorphisms in rhesus macaques on SIVmac251 setpoint viremia SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT AIDS Vaccine 2010 CY SEP 28-OCT 01, 2010 CL Atlanta, GA C1 [Zhang, G.; Brusic, V.] Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA. [Gaufin, T.; Veazey, R.] Tulane Univ, Tulane Natl Primate Res Ctr, Covington, LA USA. [Apetrei, C.; Pandrea, I.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Miller, C.] Calif Natl Primate Res Ctr, Davis, CA USA. [McCune, J.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Picker, L.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Lifson, J.; Piatak, M.] SAIC Frederick Inc, Natl Canc Inst Frederick, Frederick, MD USA. [Alter, G.] Massachusetts Gen Hosp, Ragon Inst, Charlestown, MA USA. [Barouch, D.] Beth Israel Deaconess Med Ctr, Div Vaccine Res, Boston, MD USA. [Hessell, A.; Burton, D.] Scripps Res Inst, La Jolla, CA 92037 USA. [Nimmerjahn, F.] Univ Erlangen Nurnberg, Erlangen, Germany. [Alam, M.; Haynes, B.] Duke Univ, Med Ctr, Durham, NC USA. [Finstad, S.; Jin, C.; Linde, C.; Hagan, E.; de la Rosa, M.; Zahn, R.; Wang, X.; Reimann, K.; Letvin, N.; Schmitz, J.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RI Nimmerjahn, Falk/J-4986-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2010 VL 26 IS 10 BP A20 EP A20 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 665OC UT WOS:000283044200048 ER PT J AU Gaekwad, J Kong, L Kwong, P Schief, W Dey, B Wyatt, R AF Gaekwad, J. Kong, L. Kwong, P. Schief, W. Dey, B. Wyatt, R. TI Stabilized, hyperglycosylated HIV-1 envelope glycoprotein immunogens designed to elicit antibodies against the CD4 binding site SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT AIDS Vaccine 2010 CY SEP 28-OCT 01, 2010 CL Atlanta, GA C1 [Gaekwad, J.; Kong, L.; Wyatt, R.] Scripps Res Inst, IAVI Neutralizing Antibody Ctr, San Diego, CA USA. [Kwong, P.] NIAID, Vaccine Res Ctr, Bethesda, MD 20892 USA. [Schief, W.] Univ Washington, Dept Biochem, Seattle, WA 98195 USA. [Dey, B.] NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2010 VL 26 IS 10 BP A88 EP A88 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 665OC UT WOS:000283044200219 ER PT J AU Graham, BS Ledgerwood, JE Novik, L Enama, ME Hendel, CS Nason, MC Koup, RA Mascola, JR Nabel, GJ AF Graham, B. S. Ledgerwood, J. E. Novik, L. Enama, M. E. Hendel, C. S. Nason, M. C. Koup, R. A. Mascola, J. R. Nabel, G. J. TI Safety and Immunogenicity of a rAd35-EnvA Prototype HIV-1 Vaccine in Combination with rAd5-EnvA in Healthy Adults (VRC 012) SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT AIDS Vaccine 2010 CY SEP 28-OCT 01, 2010 CL Atlanta, GA C1 [Graham, B. S.; Ledgerwood, J. E.; Novik, L.; Enama, M. E.; Hendel, C. S.; Nason, M. C.; Koup, R. A.; Mascola, J. R.; Nabel, G. J.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2010 VL 26 IS 10 BP A160 EP A161 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 665OC UT WOS:000283044200411 ER PT J AU Graham, BS Ledgerwood, JE Novik, L Enama, ME Hubka, S Koup, RA Nason, MC Mascola, JR Nabel, GJ AF Graham, B. S. Ledgerwood, J. E. Novik, L. Enama, M. E. Hubka, S. Koup, R. A. Nason, M. C. Mascola, J. R. Nabel, G. J. TI Safety and Immunogenicity of VRC rAd5 HIV-1 Vaccine Delivered Intramuscularly (IM) by Needle or Biojector Injections in Healthy Adults (VRC 015) SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT AIDS Vaccine 2010 CY SEP 28-OCT 01, 2010 CL Atlanta, GA C1 [Graham, B. S.; Ledgerwood, J. E.; Novik, L.; Enama, M. E.; Hubka, S.; Koup, R. A.; Nason, M. C.; Mascola, J. R.; Nabel, G. J.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2010 VL 26 IS 10 BP A93 EP A93 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 665OC UT WOS:000283044200233 ER PT J AU Guenaga, F Dosenovic, P Ofek, G Baker, D Schief, W Kwong, P Hedestam, GK Wyatt, R AF Guenaga, F. Dosenovic, P. Ofek, G. Baker, D. Schief, W. Kwong, P. Hedestam, G. Karlsson Wyatt, R. TI Computationally Designed Epitope-Scaffolds Focus the Humoral Immune Response to the HIV-1 2F5 Conserved Neutralization Determinant SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT AIDS Vaccine 2010 CY SEP 28-OCT 01, 2010 CL Atlanta, GA C1 [Guenaga, F.; Wyatt, R.] Scripps Res Inst, IAVI Neutralizing Antibody Ctr, San Diego, CA USA. [Dosenovic, P.; Hedestam, G. Karlsson] Karolinska Inst, Stockholm, Sweden. [Ofek, G.; Kwong, P.] NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. [Baker, D.; Schief, W.] Univ Washington, Seattle, WA 98195 USA. RI Baker, David/K-8941-2012 OI Baker, David/0000-0001-7896-6217 NR 0 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2010 VL 26 IS 10 BP A139 EP A139 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 665OC UT WOS:000283044200357 ER PT J AU Hallengard, D Applequist, S Nystrom, S Maltais, A Marovich, M Moss, B Earl, P Nihlmark, K Wahren, B Brave, A AF Hallengard, D. Applequist, S. Nystrom, S. Maltais, A. Marovich, M. Moss, B. Earl, P. Nihlmark, K. Wahren, B. Brave, A. TI Priming with plasmid DNA by electroporation and boosting with recombinant vaccinia virus Ankara induces polyfunctional immune responses in mice SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT AIDS Vaccine 2010 CY SEP 28-OCT 01, 2010 CL Atlanta, GA C1 [Hallengard, D.; Wahren, B.; Brave, A.] Karolinska Inst, Solna, Sweden. [Applequist, S.; Nystrom, S.] Karolinska Inst, Ctr Infect Med, S-10401 Stockholm, Sweden. [Marovich, M.] Walter Reed Army Inst Res, Rockville, MD USA. [Moss, B.; Earl, P.] NIAID, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2010 VL 26 IS 10 BP A92 EP A92 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 665OC UT WOS:000283044200230 ER PT J AU Harris, LD Klatt, NR Vinton, C Briant, JA Tabb, B Ladell, K Lifson, J Estes, JD Price, DA Hirsch, VM Brenchley, JM AF Harris, L. D. Klatt, N. R. Vinton, C. Briant, J. A. Tabb, B. Ladell, K. Lifson, J. Estes, J. D. Price, D. A. Hirsch, V. M. Brenchley, J. M. TI Mechanisms Underlying gamma delta T cell Subset Perturbations in SIV-infected Asian rhesus macaques SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT AIDS Vaccine 2010 CY SEP 28-OCT 01, 2010 CL Atlanta, GA C1 [Harris, L. D.; Klatt, N. R.; Vinton, C.; Briant, J. A.; Hirsch, V. M.; Brenchley, J. M.] NIAID, Bethesda, MD 20892 USA. [Tabb, B.; Lifson, J.; Estes, J. D.] SAIC Frederick Inc, NCI, AIDS & Canc Virus Program, Frederick, MD USA. [Ladell, K.; Price, D. A.] Cardiff Univ, Sch Med, Cardiff, S Glam, Wales. RI Ladell, Kristin/K-2475-2013; Price, David/C-7876-2013; Ladell, Kristin/C-8301-2013 OI Price, David/0000-0001-9416-2737; Ladell, Kristin/0000-0002-9856-2938 NR 0 TC 0 Z9 0 U1 0 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2010 VL 26 IS 10 BP A80 EP A80 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 665OC UT WOS:000283044200197 ER PT J AU Jalah, R Patel, V Kulkarni, V Valentin, A Alicea, C Rosati, M von Gegerfelt, A Sardesai, NY Bess, J Montefiori, DC Lifson, JD Pavlakis, GN Felber, BK AF Jalah, R. Patel, V. Kulkarni, V. Valentin, A. Alicea, C. Rosati, M. von Gegerfelt, A. Sardesai, N. Y. Bess, J. Montefiori, D. C. Lifson, J. D. Pavlakis, G. N. Felber, B. K. TI Improvement of humoral immune responses in macaques using DNA/viral particle combination vaccine SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT AIDS Vaccine 2010 CY SEP 28-OCT 01, 2010 CL Atlanta, GA C1 [Jalah, R.; Patel, V.; Kulkarni, V.; Valentin, A.; Alicea, C.; Rosati, M.; von Gegerfelt, A.; Pavlakis, G. N.; Felber, B. K.] NCI, Frederick, MD 21701 USA. [Sardesai, N. Y.] Inovio Biomed Corp, Blue Bell, PA USA. [Bess, J.; Lifson, J. D.] SAIC Frederick Inc, AIDS & Canc Virus Program, Frederick, MD USA. [Montefiori, D. C.] Duke Univ, Med Ctr, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2010 VL 26 IS 10 BP A118 EP A118 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 665OC UT WOS:000283044200300 ER PT J AU Kanekiyo, M Panet, A Xu, L Boyington, JC Louder, MK Yang, Z Mascola, JR Nabel, GJ AF Kanekiyo, M. Panet, A. Xu, L. Boyington, J. C. Louder, M. K. Yang, Z. Mascola, J. R. Nabel, G. J. TI Molecular design and biochemical characterization of HIV-1 clade C Env gp120 derivatives SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT AIDS Vaccine 2010 CY SEP 28-OCT 01, 2010 CL Atlanta, GA C1 [Kanekiyo, M.; Panet, A.; Xu, L.; Boyington, J. C.; Louder, M. K.; Yang, Z.; Mascola, J. R.; Nabel, G. J.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2010 VL 26 IS 10 BP A156 EP A157 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 665OC UT WOS:000283044200401 ER PT J AU Klatt, NR Harris, L Vinton, C Morcock, D Tabb, B Sung, H Lifson, J Martin, M Levine, A Alter, G Estes, J Brenchley, J AF Klatt, N. R. Harris, L. Vinton, C. Morcock, D. Tabb, B. Sung, H. Lifson, J. Martin, M. Levine, A. Alter, G. Estes, J. Brenchley, J. TI SIV infection results in loss of IL-17-producing NK cells in mucosal tissues, which contributes to damage to the mucosal barrier SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT AIDS Vaccine 2010 CY SEP 28-OCT 01, 2010 CL Atlanta, GA C1 [Klatt, N. R.; Harris, L.; Vinton, C.; Martin, M.; Brenchley, J.] NIAID, NIH, Bethesda, MD 20892 USA. [Morcock, D.; Tabb, B.; Lifson, J.; Estes, J.] NCI, SAIC Inc, Frederick, MD 21701 USA. [Sung, H.; Levine, A.] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Alter, G.] Harvard Univ, Ragon Inst, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2010 VL 26 IS 10 BP A22 EP A22 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 665OC UT WOS:000283044200053 ER PT J AU Ko, S Kong, W Wang, L Cheng, C Gall, J King, C Nabel, GJ AF Ko, S. Kong, W. Wang, L. Cheng, C. Gall, J. King, C. Nabel, G. J. TI Recombinant simian adenovirus vectors for the development of alternative Ad5 HIV vaccines SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT AIDS Vaccine 2010 CY SEP 28-OCT 01, 2010 CL Atlanta, GA C1 [Ko, S.; Kong, W.; Wang, L.; Cheng, C.; Nabel, G. J.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Gall, J.; King, C.] GenVec Inc, Gaithersburg, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2010 VL 26 IS 10 BP A118 EP A118 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 665OC UT WOS:000283044200301 ER PT J AU Kulkarni, V Valentin, A Yan, J Rolland, M Le Gall, S Mothe, B Ganneru, B Patel, V Zhang, G Rosati, M Pankhong, P Elliott, S Harris, A Manocheewa, S Sardesai, NY Weiner, DB Brander, C Pavlakis, GN Felber, BK Mullins, JI AF Kulkarni, V. Valentin, A. Yan, J. Rolland, M. Le Gall, S. Mothe, B. Ganneru, B. Patel, V. Zhang, G. Rosati, M. Pankhong, P. Elliott, S. Harris, A. Manocheewa, S. Sardesai, N. Y. Weiner, D. B. Brander, C. Pavlakis, G. N. Felber, B. K. Mullins, J. I. TI Conserved Elements Vaccine for HIV-1 p24gag is immunogenic in mice and macaques SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT AIDS Vaccine 2010 CY SEP 28-OCT 01, 2010 CL Atlanta, GA C1 [Kulkarni, V.; Valentin, A.; Ganneru, B.; Patel, V.; Zhang, G.; Rosati, M.; Pavlakis, G. N.; Felber, B. K.] NCI, Frederick, MD 21701 USA. [Yan, J.; Pankhong, P.; Elliott, S.; Harris, A.; Weiner, D. B.] Univ Penn, Philadelphia, PA 19104 USA. [Rolland, M.; Manocheewa, S.; Mullins, J. I.] Univ Washington, Seattle, WA 98195 USA. [Le Gall, S.] Ragon Inst, Boston, MA USA. [Mothe, B.; Brander, C.] IrsiCaixa HI VACAT, Barcelona, Spain. [Sardesai, N. Y.] Inovio Biomed Corp, Blue Bell, PA USA. RI Weiner, David/H-8579-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2010 VL 26 IS 10 BP A120 EP A120 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 665OC UT WOS:000283044200306 ER PT J AU Kwong, PD Yang, Y Zhou, T Burton, DR Koff, WC Phogat, S Poignard, P Simek, M Louder, M McKee, K Nabel, GJ Wu, L Yang, Z Hogerkorp, C Roederer, M Wu, X Mascola, JR AF Kwong, P. D. Yang, Y. Zhou, T. Burton, D. R. Koff, W. C. Phogat, S. Poignard, P. Simek, M. Louder, M. McKee, K. Nabel, G. J. Wu, L. Yang, Z. Hogerkorp, C. Roederer, M. Wu, X. Mascola, J. R. TI Affinity maturation allows VRC01-like antibodies to converge on a common mode of effective HIV-1 neutralization SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT AIDS Vaccine 2010 CY SEP 28-OCT 01, 2010 CL Atlanta, GA C1 [Kwong, P. D.; Yang, Y.; Zhou, T.; Louder, M.; McKee, K.; Nabel, G. J.; Wu, L.; Yang, Z.; Hogerkorp, C.; Roederer, M.; Wu, X.; Mascola, J. R.] NIADI, Vaccine Res Ctr, NIH, Bethesda, MD USA. [Burton, D. R.; Koff, W. C.; Phogat, S.; Poignard, P.; Simek, M.] Int AIDS Vaccine Initiat, La Jolla, CA USA. RI Zhou, Tongqing/A-6880-2010; poignard, pascal/N-6678-2013 OI Zhou, Tongqing/0000-0002-3935-4637; NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2010 VL 26 IS 10 BP A31 EP A32 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 665OC UT WOS:000283044200074 ER PT J AU Lai, L Kwa, S Siddiqui, M Chennareddi, L Montefiori, D Kozlowski, P Wyatt, L Moss, B Robinson, H Amara, R AF Lai, L. Kwa, S. Siddiqui, M. Chennareddi, L. Montefiori, D. Kozlowski, P. Wyatt, L. Moss, B. Robinson, H. Amara, R. TI Preclinical Studies on DNA/MVA Vaccines, Co-expressed GM-CSF, a Strong Adjuvant for Prevention of Acquisition SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT AIDS Vaccine 2010 CY SEP 28-OCT 01, 2010 CL Atlanta, GA C1 [Lai, L.; Kwa, S.; Siddiqui, M.; Chennareddi, L.; Amara, R.] Emory Univ, Atlanta, GA 30322 USA. [Montefiori, D.] Duke Univ, Med Ctr, Durham, NC USA. [Kozlowski, P.] LSUHSC, Gene Therapy Program, New Orleans, LA USA. [Wyatt, L.; Moss, B.] NIAID, NIH, Bethesda, MD 20892 USA. [Robinson, H.] Geovax Labs Inc, Atlanta, GA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2010 VL 26 IS 10 BP A92 EP A93 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 665OC UT WOS:000283044200231 ER PT J AU Li, Q Duan, L Southern, P Piatak, M Lifson, J Reeves, R Johnson, R Haase, A AF Li, Q. Duan, L. Southern, P. Piatak, M. Lifson, J. Reeves, R. Johnson, R. Haase, A. TI Dissecting the Protective Mechanisms in Cervicovaginal Tissues of SIVmac239 Gamma nef-Vaccinated Macaques against Pathogenic SIV Challenge SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT AIDS Vaccine 2010 CY SEP 28-OCT 01, 2010 CL Atlanta, GA C1 [Li, Q.] Univ Minnesota, Shoreview, MN USA. [Duan, L.; Southern, P.; Haase, A.] Univ Minnesota, Sch Med, Dept Microbiol, Minneapolis, MN 55455 USA. [Piatak, M.; Lifson, J.] NCI, AIDS & Canc Virus Program, SAIC Frederick Inc, Frederick, MD 21701 USA. [Reeves, R.; Johnson, R.] Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Southborough, MA 01772 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2010 VL 26 IS 10 BP A22 EP A22 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 665OC UT WOS:000283044200052 ER PT J AU Li, Y Walker, LM Wu, X O'Dell, S Guenaga, J Chakrabarti, B Feng, Y Schmidt, S McKee, K Louder, MK Wycuff, D Burton, D Wyatt, RT Mascola, JR AF Li, Y. Walker, L. M. Wu, X. O'Dell, S. Guenaga, J. Chakrabarti, B. Feng, Y. Schmidt, S. McKee, K. Louder, M. K. Wycuff, D. Burton, D. Wyatt, R. T. Mascola, J. R. TI Mechanism of neutralization by monoclonal antibody VRC01, a CD4 binding site directed neutralizing antibody with extensive neutralization breadth SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT AIDS Vaccine 2010 CY SEP 28-OCT 01, 2010 CL Atlanta, GA C1 [Li, Y.; Wu, X.; O'Dell, S.; Schmidt, S.; McKee, K.; Louder, M. K.; Wycuff, D.; Mascola, J. R.] NIAID, NIH, Bethesda, MD 20892 USA. [Walker, L. M.; Guenaga, J.; Chakrabarti, B.; Feng, Y.; Burton, D.; Wyatt, R. T.] Scripps Res Inst, La Jolla, CA 92037 USA. [Walker, L. M.; Guenaga, J.; Chakrabarti, B.; Feng, Y.; Burton, D.; Wyatt, R. T.] Neutralizing Antibody Ctr, Int AIDS Vaccine Initiat IAVI, La Jolla, CA USA. RI Feng, Yu/A-3396-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2010 VL 26 IS 10 BP A24 EP A24 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 665OC UT WOS:000283044200057 ER PT J AU Liu, J Keele, BF Liu, H Keating, S Norris, PJ Carville, A Mansfield, KG Tomaras, GD Haynes, BF Letvin, NL Hahn, BH Shaw, GM Barouch, DH AF Liu, J. Keele, B. F. Liu, H. Keating, S. Norris, P. J. Carville, A. Mansfield, K. G. Tomaras, G. D. Haynes, B. F. Letvin, N. L. Hahn, B. H. Shaw, G. M. Barouch, D. H. TI Low Dose Mucosal SIV Infection Restricts Early Replication Kinetics and Transmitted Virus Variants in Rhesus Monkeys SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT AIDS Vaccine 2010 CY SEP 28-OCT 01, 2010 CL Atlanta, GA C1 [Liu, J.] Harvard Univ, Sch Med, Boston, MA USA. [Keele, B. F.] NCI, SAIC Frederick, Frederick, MD 21701 USA. [Liu, H.; Hahn, B. H.; Shaw, G. M.] Univ Alabama, Birmingham, AL USA. [Keating, S.; Norris, P. J.] Blood Syst Res Inst, San Francisco, CA USA. [Keating, S.; Norris, P. J.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Carville, A.; Mansfield, K. G.] Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Southborough, MA 01772 USA. [Tomaras, G. D.; Haynes, B. F.] Duke Univ, Med Ctr, Duke Human Vaccine Inst, Durham, NC USA. [Letvin, N. L.] Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis, Boston, MA 02215 USA. [Barouch, D. H.] MGH MIT & Harvard, Ragon Inst, BIDMC, Div Vaccine Res, Boston, MA USA. RI Tomaras, Georgia/J-5041-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2010 VL 26 IS 10 BP A29 EP A29 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 665OC UT WOS:000283044200070 ER PT J AU Liu, L Cimbro, R Lusso, P Berger, EA AF Liu, L. Cimbro, R. Lusso, P. Berger, E. A. TI Mechanism of V3 Epitope Masking Within the HIV-1 Env Trimer SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT AIDS Vaccine 2010 CY SEP 28-OCT 01, 2010 CL Atlanta, GA C1 [Cimbro, R.; Lusso, P.] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2010 VL 26 IS 10 BP A55 EP A56 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 665OC UT WOS:000283044200133 ER PT J AU McVey, D Kahl, C Limbach, P Balsley, N Fultz, M Hiriyanna, S Glenn, A Hoffman, C McCullough, T Moore, V Semonova, E Kumar, SV Cheng, C Kong, W Ko, S Wang, L Nabel, GJ Gall, J AF McVey, D. Kahl, C. Limbach, P. Balsley, N. Fultz, M. Hiriyanna, S. Glenn, A. Hoffman, C. McCullough, T. Moore, V. Semonova, E. Kumar, S. Vinod Cheng, C. Kong, W. Ko, S. Wang, L. Nabel, G. J. Gall, J. TI Simian Adenoviruses as Vaccine Vectors for HIV SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT AIDS Vaccine 2010 CY SEP 28-OCT 01, 2010 CL Atlanta, GA C1 [Cheng, C.; Kong, W.; Ko, S.; Wang, L.; Nabel, G. J.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [McVey, D.; Kahl, C.; Limbach, P.; Balsley, N.; Fultz, M.; Hiriyanna, S.; Glenn, A.; Hoffman, C.; McCullough, T.; Moore, V.; Semonova, E.; Kumar, S. Vinod; Gall, J.] GenVec Inc, Gaithersburg, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2010 VL 26 IS 10 BP A127 EP A128 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 665OC UT WOS:000283044200326 ER PT J AU Mendoza, D Migueles, SA Rood, JE Doria-Rose, NA Franchini, G Schneider, D Trivett, MT Trubey, CM Coalter, V Rakasz, EG Watkins, DI Lifson, JD Connors, M AF Mendoza, D. Migueles, S. A. Rood, J. E. Doria-Rose, N. A. Franchini, G. Schneider, D. Trivett, M. T. Trubey, C. M. Coalter, V. Rakasz, E. G. Watkins, D. I. Lifson, J. D. Connors, M. TI Cytotoxic Capacity of SIV-Specific-CD8+T Cells from SIV-Infected Rhesus Macaques Measured Against Primary Autologous CD4+T Cells SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT AIDS Vaccine 2010 CY SEP 28-OCT 01, 2010 CL Atlanta, GA C1 [Mendoza, D.; Migueles, S. A.; Rood, J. E.; Doria-Rose, N. A.; Connors, M.] NIAID, NIH, Bethesda, MD 20892 USA. [Franchini, G.] NCI, Vaccine Branch, NIH, Bethesda, MD 20892 USA. [Schneider, D.; Trivett, M. T.; Trubey, C. M.; Coalter, V.; Lifson, J. D.] SAIC Frederick Inc, AIDS & Canc Virus Program, Frederick, MD USA. [Rakasz, E. G.; Watkins, D. I.] Univ Wisconsin, Dept Pathol & Lab Med, Madison, WI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2010 VL 26 IS 10 BP A42 EP A42 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 665OC UT WOS:000283044200100 ER PT J AU Moodley, R Alter, G Werner, L Mlisana, K Martin, MP Rosa, DDA Gray, C Carrington, M Walker, B Karim, SS Altfeld, M Ndung'u, T AF Moodley, R. Alter, G. Werner, L. Mlisana, K. Martin, M. P. Rosa, D. D. Assa Gray, C. Carrington, M. Walker, B. Karim, S. S. Altfeld, M. Ndung'u, T. TI Ligand Dependant Increase in KIR Gene Expression in Primary HIV-1 Infection SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT AIDS Vaccine 2010 CY SEP 28-OCT 01, 2010 CL Atlanta, GA C1 [Moodley, R.; Ndung'u, T.] Univ KwaZulu Natal, Durban, Kwazulu Natal, South Africa. [Alter, G.] MIT, MGH, Ragon Inst, Boston, MA USA. [Alter, G.] Harvard Infect Dis Unit, Boston, MA USA. [Werner, L.; Mlisana, K.; Karim, S. S.] CAPRISA, Durban, Kwazulu Natal, South Africa. [Martin, M. P.; Carrington, M.] NCI, SAIC Frederick, Frederick, MD 21701 USA. [Rosa, D. D. Assa; Gray, C.] NICD, Johannesburg, South Africa. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2010 VL 26 IS 10 BP A12 EP A13 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 665OC UT WOS:000283044200028 ER PT J AU Mullins, JI Pavlakis, GN Felber, BK Brander, C Le Gall, S Weiner, D Stone, G Rolland, M Kulkarni, V Mothe, B Yan, J Heckerman, D Ganneru, B Zhang, G Singh, A Rosati, M Pankhong, P Lanxon-Cookson, E Swain, V Elliot, S Manocheewa, S Zhang, S Gonzalez, T Zamarreno, J Llano, A Ibarrondo, J Herrero, J Palou, E Clotet, B Gel, S AF Mullins, J. I. Pavlakis, G. N. Felber, B. K. Brander, C. Le Gall, S. Weiner, D. Stone, G. Rolland, M. Kulkarni, V. Mothe, B. Yan, J. Heckerman, D. Ganneru, B. Zhang, G. Singh, A. Rosati, M. Pankhong, P. Lanxon-Cookson, E. Swain, V. Elliot, S. Manocheewa, S. Zhang, S. Gonzalez, T. Zamarreno, J. Llano, A. Ibarrondo, J. Herrero, J. Palou, E. Clotet, B. Gel, S. TI A Global AIDS Vaccine Based on Conserved Elements of the Viral Proteome SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT AIDS Vaccine 2010 CY SEP 28-OCT 01, 2010 CL Atlanta, GA C1 [Mullins, J. I.; Rolland, M.; Lanxon-Cookson, E.; Swain, V.; Manocheewa, S.] Univ Washington, Seattle, WA 98195 USA. [Pavlakis, G. N.; Felber, B. K.; Kulkarni, V.; Ganneru, B.; Zhang, G.; Singh, A.; Rosati, M.] NCI, Frederick, MD 21701 USA. [Brander, C.; Mothe, B.; Gonzalez, T.; Zamarreno, J.; Llano, A.; Ibarrondo, J.; Herrero, J.; Palou, E.; Clotet, B.] Irsi Caixa HIVACAT, Barcelona, Spain. [Le Gall, S.; Zhang, S.] Ragon Inst, Boston, MA USA. [Weiner, D.; Yan, J.; Pankhong, P.; Elliot, S.] Univ Penn, Philadelphia, PA 19104 USA. [Stone, G.] Univ Miami, Miami, FL USA. [Heckerman, D.] Microsoft Res, Los Angeles, CA USA. [Gel, S.] Fundacio Lluita Sida, Barcelona, Spain. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2010 VL 26 IS 10 BP A2 EP A2 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 665OC UT WOS:000283044200002 ER PT J AU Olshevsky, U Pegu, A McTamney, P Yang, Z McKee, K Mascola, J Nabel, G AF Olshevsky, U. Pegu, A. McTamney, P. Yang, Z. McKee, K. Mascola, J. Nabel, G. TI Neutralization of HIV-1 by an IgM antibody expressing the VRC01 V region SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT AIDS Vaccine 2010 CY SEP 28-OCT 01, 2010 CL Atlanta, GA C1 [Olshevsky, U.; Pegu, A.; McTamney, P.; Yang, Z.; McKee, K.; Mascola, J.; Nabel, G.] NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2010 VL 26 IS 10 BP A155 EP A155 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 665OC UT WOS:000283044200397 ER PT J AU Parker, S Elizaga, M Kim, D Metch, B Allen, M De Rosa, S Hural, J Torres, K Boyer, J Joseph, P Weiner, DB Kalams, S AF Parker, S. Elizaga, M. Kim, D. Metch, B. Allen, M. De Rosa, S. Hural, J. Torres, K. Boyer, J. Joseph, P. Weiner, D. B. Kalams, S. TI Phase I trial of a prophylactic HIV-1 gag-pol-env DNA plasmid vaccine with IL-12 or IL-15 DNA molecular adjuvants (HVTN 070) SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT AIDS Vaccine 2010 CY SEP 28-OCT 01, 2010 CL Atlanta, GA C1 [Parker, S.] Univ Alabama, Birmingham, AL USA. [Elizaga, M.; Metch, B.; De Rosa, S.; Hural, J.; Torres, K.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. [Kim, D.] Takeda Pharmaceut N Amer, Deerfield, IL USA. [Allen, M.] NIAID, Bethesda, MD 20892 USA. [Boyer, J.; Weiner, D. B.] Univ Penn, Philadelphia, PA 19104 USA. [Joseph, P.] GHESKIO Ctr, Port Au Prince, Haiti. [Kalams, S.] Vanderbilt Univ, Nashville, TN USA. RI Weiner, David/H-8579-2014 NR 0 TC 0 Z9 0 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2010 VL 26 IS 10 BP A91 EP A91 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 665OC UT WOS:000283044200228 ER PT J AU Patel, V Kulkarni, V Jalah, R Valentin, A Alicea, C Rosati, M von Gegerfelt, A Sardesai, NY Robert-Guroff, M Montefiori, DC Ohlen, C Pavlakis, GN Felber, BK AF Patel, V. Kulkarni, V. Jalah, R. Valentin, A. Alicea, C. Rosati, M. von Gegerfelt, A. Sardesai, N. Y. Robert-Guroff, M. Montefiori, D. C. Ohlen, C. Pavlakis, G. N. Felber, B. K. TI Improved DNA vaccination achieves long-lasting immune responses in macaques SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT AIDS Vaccine 2010 CY SEP 28-OCT 01, 2010 CL Atlanta, GA C1 [Patel, V.; Kulkarni, V.; Jalah, R.; Valentin, A.; Alicea, C.; Rosati, M.; von Gegerfelt, A.; Ohlen, C.; Pavlakis, G. N.; Felber, B. K.] NCI, Frederick, MD 21701 USA. [Sardesai, N. Y.] Inovio Biomed Corp, Blue Bell, PA USA. [Robert-Guroff, M.] NCI, Bethesda, MD 20892 USA. [Montefiori, D. C.] Duke Univ, Med Ctr, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2010 VL 26 IS 10 BP A120 EP A121 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 665OC UT WOS:000283044200307 ER PT J AU Pavlakis, GN Valentin, A Rosati, M Patel, V Jalah, R Kulkarni, V Alicea, C von Gegerfelt, A Sardesai, NY Montefiori, DC Lifson, JD Felber, BK AF Pavlakis, G. N. Valentin, A. Rosati, M. Patel, V. Jalah, R. Kulkarni, V. Alicea, C. von Gegerfelt, A. Sardesai, N. Y. Montefiori, D. C. Lifson, J. D. Felber, B. K. TI DNA and combination vaccines achieve high levels of long lasting and protective cellular and humoral responses SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT AIDS Vaccine 2010 CY SEP 28-OCT 01, 2010 CL Atlanta, GA C1 [Sardesai, N. Y.] Inovio Biomed Corp, Blue Bell, PA USA. [Montefiori, D. C.] Duke Univ, Med Ctr, Durham, NC USA. [Lifson, J. D.] NCI, SAIC, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2010 VL 26 IS 10 BP A123 EP A124 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 665OC UT WOS:000283044200315 ER PT J AU Qureshi, H Genesca, M Fritts, L Li, J Casimiro, DR Shiver, JW Bett, AJ DiPasquale, J Guroff, MR McChesney, MB Miller, CJ AF Qureshi, H. Genesca, M. Fritts, L. Li, J. Casimiro, D. R. Shiver, J. W. Bett, A. J. DiPasquale, J. Guroff, M. R. McChesney, M. B. Miller, C. J. TI Transient but recurrent CD4+T cell activation, T cell immunity and neutralizing antibody responses after Ad5 infection of rhesus macaques SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT AIDS Vaccine 2010 CY SEP 28-OCT 01, 2010 CL Atlanta, GA C1 [Qureshi, H.; Genesca, M.; Fritts, L.; Li, J.; McChesney, M. B.; Miller, C. J.] Calif Natl Primate Res Ctr, Davis, CA USA. [Qureshi, H.; Genesca, M.; Fritts, L.; Li, J.; Miller, C. J.] CCM, Davis, CA USA. [Casimiro, D. R.; Shiver, J. W.; Bett, A. J.] Merck Res Labs, West Point, PA USA. [DiPasquale, J.; Guroff, M. R.] NCI, NIH, Vaccine Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2010 VL 26 IS 10 BP A121 EP A121 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 665OC UT WOS:000283044200308 ER PT J AU Smalls-Mantey, AR Klein, RM Doria-Rose, NA Laub, LB Rood, JE Migueles, SA Mascola, JR Sattentau, QJ Connors, M AF Smalls-Mantey, A. R. Klein, R. M. Doria-Rose, N. A. Laub, L. B. Rood, J. E. Migueles, S. A. Mascola, J. R. Sattentau, Q. J. Connors, M. TI HIV-Specific Antibodies Mediate Rapid Antibody-Dependent Cellular Cytotoxicity Against Primary HIV-Infected CD4+T Cells SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT AIDS Vaccine 2010 CY SEP 28-OCT 01, 2010 CL Atlanta, GA C1 [Mascola, J. R.] NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. [Sattentau, Q. J.] Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2010 VL 26 IS 10 BP A80 EP A81 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 665OC UT WOS:000283044200199 ER PT J AU Tsao, C Liao, H Ma, B Chen, H Foulger, AS Lu, X Jaeger, F Hahn, B Shaw, G Swanstrom, R Cohen, M Kamanga, G Mascola, J Montefiori, D Alam, MS Haynes, BF AF Tsao, C. Liao, H. Ma, B. Chen, H. Foulger, A. S. Lu, X. Jaeger, F. Hahn, B. Shaw, G. Swanstrom, R. Cohen, M. Kamanga, G. Mascola, J. Montefiori, D. Alam, M. S. Haynes, B. F. TI Antigenicity and immunogenicity of transmitted/founder HIV envelope oligomers compared to chronic HIV envelopes SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT AIDS Vaccine 2010 CY SEP 28-OCT 01, 2010 CL Atlanta, GA C1 [Tsao, C.; Liao, H.; Ma, B.; Chen, H.; Foulger, A. S.; Lu, X.; Jaeger, F.; Alam, M. S.; Haynes, B. F.] Duke Human Vaccine Inst, Durham, NC USA. [Hahn, B.; Shaw, G.] Univ Alabama, Div Hematol Oncol, Birmingham, AL 35294 USA. [Swanstrom, R.] Univ N Carolina, Ctr AIDS Res, Chapel Hill, NC USA. [Cohen, M.] Univ N Carolina, Ctr Infect Dis, Chapel Hill, NC USA. [Kamanga, G.] Univ N Carolina Project, Lilongwe, Malawi. [Mascola, J.] NIH, Bethesda, MD 20892 USA. [Montefiori, D.] Duke Med Ctr, Lab AIDS Vaccine Res & Dev, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2010 VL 26 IS 10 BP A26 EP A26 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 665OC UT WOS:000283044200062 ER PT J AU von Gegerfelt, A Valentin, A Alicea, C Van Rompay, KK Marthas, ML Montefiori, DC Pavlakis, GN Felber, BK AF von Gegerfelt, A. Valentin, A. Alicea, C. Van Rompay, K. K. Marthas, M. L. Montefiori, D. C. Pavlakis, G. N. Felber, B. K. TI SIV-Specific Cytotoxic CD4+T Cells and Humoral Responses Control Rebounding Viremia in CD8-Depleted Macaques Infected with Rev-Independent SIV SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT AIDS Vaccine 2010 CY SEP 28-OCT 01, 2010 CL Atlanta, GA C1 [Van Rompay, K. K.; Marthas, M. L.] Univ Calif Davis, Calif Natl Primate Res Ctr, Davis, CA 95616 USA. [Montefiori, D. C.] Duke Univ, Med Ctr, Durham, NC USA. [von Gegerfelt, A.; Valentin, A.; Alicea, C.; Pavlakis, G. N.; Felber, B. K.] NCI, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2010 VL 26 IS 10 BP A112 EP A112 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 665OC UT WOS:000283044200285 ER PT J AU Wilks, AB Carville, A Sircar, P Seaman, MS Barouch, DH Nabel, GJ Letvin, NL Permar, S AF Wilks, A. B. Carville, A. Sircar, P. Seaman, M. S. Barouch, D. H. Nabel, G. J. Letvin, N. L. Permar, S. TI Vaccine-elicited SIV-specific cellular and humoral immune responses in breast milk of lactating rhesus monkeys after systemic SIV vaccination SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT AIDS Vaccine 2010 CY SEP 28-OCT 01, 2010 CL Atlanta, GA C1 [Carville, A.] New England Reg Primate Res Ctr, Southborough, MA 01772 USA. [Nabel, G. J.] NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. [Wilks, A. B.; Sircar, P.; Seaman, M. S.; Barouch, D. H.; Letvin, N. L.; Permar, S.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2010 VL 26 IS 10 BP A85 EP A86 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 665OC UT WOS:000283044200213 ER PT J AU Wu, L Yang, Z Ko, S Shi, W Chen, X Wu, X O'Dell, S Louder, M Nguyen, R Perfetto, S Roederer, M Mascola, JR Nabel, GJ AF Wu, L. Yang, Z. Ko, S. Shi, W. Chen, X. Wu, X. O'Dell, S. Louder, M. Nguyen, R. Perfetto, S. Roederer, M. Mascola, J. R. Nabel, G. J. TI Development of monoclonal antibodies specific for affinity matured and germ line variants of the potent anti-HIV neutralization antibody VRC01 SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT AIDS Vaccine 2010 CY SEP 28-OCT 01, 2010 CL Atlanta, GA C1 [Wu, L.; Yang, Z.; Ko, S.; Shi, W.] NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2010 VL 26 IS 10 BP A153 EP A153 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 665OC UT WOS:000283044200392 ER PT J AU Wu, X Wang, C Zhu, J O'Dell, S Keele, B Pham, K Yang, Z Zhou, T Imamichi, H Doria-Rose, N Kwong, PD Hoxie, JA Connors, M Shaw, GM Mascola, JR AF Wu, X. Wang, C. Zhu, J. O'Dell, S. Keele, B. Pham, K. Yang, Z. Zhou, T. Imamichi, H. Doria-Rose, N. Kwong, P. D. Hoxie, J. A. Connors, M. Shaw, G. M. Mascola, J. R. TI Characterization of HIV-1 envelope variants from slow progressors who developed broadly neutralizing CD4-binding site antibodies against HIV-1 SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT AIDS Vaccine 2010 CY SEP 28-OCT 01, 2010 CL Atlanta, GA C1 [Imamichi, H.; Doria-Rose, N.; Connors, M.] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. [Keele, B.] NCI, NIH, Frederick, MD 21701 USA. [Pham, K.; Shaw, G. M.] Univ Alabama, Birmingham, AL USA. [Hoxie, J. A.] Univ Penn, Philadelphia, PA 19104 USA. RI Zhou, Tongqing/A-6880-2010 OI Zhou, Tongqing/0000-0002-3935-4637 NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2010 VL 26 IS 10 BP A56 EP A56 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 665OC UT WOS:000283044200134 ER PT J AU Xu, L Boyington, JC Zhou, T Zhu, J Wu, L Louder, MK Akahata, W Kwong, PD Mascola, JR Yang, Z Nabel, GJ AF Xu, L. Boyington, J. C. Zhou, T. Zhu, J. Wu, L. Louder, M. K. Akahata, W. Kwong, P. D. Mascola, J. R. Yang, Z. Nabel, G. J. TI Optimization of the Outer Domain of gp120 as an HIV-1 Vaccine Immunogen SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT AIDS Vaccine 2010 CY SEP 28-OCT 01, 2010 CL Atlanta, GA C1 [Xu, L.; Boyington, J. C.; Zhou, T.; Zhu, J.] NIAID, NIH, VRC, Bethesda, MD 20892 USA. RI Zhou, Tongqing/A-6880-2010 OI Zhou, Tongqing/0000-0002-3935-4637 NR 0 TC 1 Z9 1 U1 0 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2010 VL 26 IS 10 BP A166 EP A167 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 665OC UT WOS:000283044200427 ER PT J AU Yang, Z Schief, WR Zhou, T Schmidt, SD Wu, L Xu, L Wu, X Mckee, K Sijy, O Louder, MK Doria-Rose, N Connors, M Kwong, PD Mascola, JR Nabel, GJ AF Yang, Z. Schief, W. R. Zhou, T. Schmidt, S. D. Wu, L. Xu, L. Wu, X. Mckee, K. Sijy, O. Louder, M. K. Doria-Rose, N. Connors, M. Kwong, P. D. Mascola, J. R. Nabel, G. J. TI Detection and Characterization of CD4 BS Antibodies in Human Sera Using Resurfaced Stabilized Cores SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT AIDS Vaccine 2010 CY SEP 28-OCT 01, 2010 CL Atlanta, GA C1 [Yang, Z.; Zhou, T.; Schmidt, S. D.; Wu, L.; Xu, L.; Wu, X.; Mckee, K.; Sijy, O.; Louder, M. K.; Kwong, P. D.; Mascola, J. R.; Nabel, G. J.] NIAID, Vector Core Lab, VRC, NIH, Bethesda, MD 20892 USA. [Schief, W. R.] Univ Washington, Dept Biochem, Seattle, WA 98195 USA. [Doria-Rose, N.; Connors, M.] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2010 VL 26 IS 10 BP A153 EP A154 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 665OC UT WOS:000283044200393 ER PT J AU Zhu, Z Qin, HR Chen, W Zhao, Q Fouda, G Schutte, R Shen, X Liao, H Ofek, G Owens, J Streaker, E Wang, Y Kwong, PD Montefiori, DC Haynes, BF Tomaras, GD Dimitrov, DS AF Zhu, Z. Qin, H. R. Chen, W. Zhao, Q. Fouda, G. Schutte, R. Shen, X. Liao, H. Ofek, G. Owens, J. Streaker, E. Wang, Y. Kwong, P. D. Montefiori, D. C. Haynes, B. F. Tomaras, G. D. Dimitrov, D. S. TI New broadly neutralizing human monoclonal antibodies targeting the 2F5 epitope SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT AIDS Vaccine 2010 CY SEP 28-OCT 01, 2010 CL Atlanta, GA C1 [Zhu, Z.; Qin, H. R.; Chen, W.; Zhao, Q.; Shen, X.; Liao, H.; Owens, J.; Streaker, E.; Wang, Y.; Dimitrov, D. S.] NCI Frederick NIH, Frederick, MD USA. [Fouda, G.; Schutte, R.; Montefiori, D. C.; Haynes, B. F.; Tomaras, G. D.] Human Vaccine Inst, Durham, NC USA. [Ofek, G.; Kwong, P. D.] Vaccine Res Ctr, Bethesda, MD USA. RI Tomaras, Georgia/J-5041-2016 NR 0 TC 2 Z9 2 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2010 VL 26 IS 10 BP A14 EP A15 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 665OC UT WOS:000283044200034 ER PT J AU Szabo, G Wands, JR Eken, A Osna, NA Weinman, SA Machida, K Wang, HJ AF Szabo, Gyongyi Wands, Jack R. Eken, Ahmet Osna, Natalia A. Weinman, Steven A. Machida, Keigo Wang, H. Joe TI Alcohol and Hepatitis C Virus-Interactions in Immune Dysfunctions and Liver Damage SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Review DE Antigen-Presenting Cells; CD4+T Cells; CD8+T Cells; Cytotoxic T Lymphocytes (CTL); Cytokines; CYP2E1; Dendritic Cells (DCs); HCV; HCV Core Protein; NS5a Protein; Hepatocytes; Hepatocellular Carcinoma (HCC); Innate and Adaptive Immunity; Lieber-DeCarli diet; Lipopolysaccharide (LPS); Mitochondrial Ca2+; Mitochondrial Dysfunction; Mn-Superoxide Dismutase (SOD2); Proteasome; Reactive Oxygen Species (ROS); Toll-Like Receptor 4 (TLR4); Transgenic Mice ID INDUCED OXIDATIVE STRESS; CANCER STEM-CELLS; MANGANESE SUPEROXIDE-DISMUTASE; CYTOKINE-EXPRESSING PLASMIDS; CHRONIC ETHANOL-CONSUMPTION; NONSTRUCTURAL PROTEIN 4A; CHRONIC HCV INFECTION; CORE PROTEIN; HEPATOCELLULAR-CARCINOMA; DENDRITIC CELLS AB Hepatitis C virus infection affects 170 million people worldwide, and the majority of individuals exposed to HCV develop chronic hepatitis leading to progressive liver damage, cirrhosis, and hepatocellular cancer. The natural history of HCV infection is influenced by genetic and environmental factors of which chronic alcohol use is an independent risk factor for cirrhosis in HCV-infected individuals. Both the hepatitis C virus and alcohol damage the liver and result in immune alterations contributing to both decreased viral clearance and liver injury. This review will capture the major components of the interactions between alcohol and HCV infection to provide better understanding for the molecular basis of the dangerous combination of alcohol use and HCV infection. Common targets of HCV and alcohol involve innate immune recognition and dendritic cells, the critical cell type in antigen presentation and antiviral immunity. In addition, both alcohol and HCV affect intracellular processes critical for hepatocyte and immune cell functions including mitochondrial and proteasomal activation. Finally, both chronic alcohol use and hepatitis C virus infection increase the risk of hepatocellular cancer. The common molecular mechanisms underlying the pathological interactions between alcohol and HCV include the modulation of cytokine production, lipopolysaccharide (LPS)-TLR4 signaling, and reactive oxygen species (ROS) production. LPS-induced chronic inflammation is not only a major cause of progressive liver injury and fibrosis, but it can also contribute to modification of the tissue environment and stem cells to promote hepatocellular cancer development. Alteration of these processes by alcohol and HCV produces an environment of impaired antiviral immune response, greater hepatocellular injury, and activation of cell proliferation and dedifferentiation. C1 [Szabo, Gyongyi] Univ Massachusetts, Sch Med, Dept Med, Worcester, MA USA. [Wands, Jack R.; Eken, Ahmet] Brown Alpert Med Sch, Liver Res Ctr, Providence, RI USA. [Wands, Jack R.; Eken, Ahmet] Rhode Isl Hosp, Providence, RI USA. [Osna, Natalia A.] Univ Nebraska Med Ctr, Dept Internal Med, Omaha, NE USA. [Osna, Natalia A.] VA Med Ctr, Omaha, NE USA. [Weinman, Steven A.] Univ Kansas, Med Ctr, Ctr Liver, Kansas City, KS 66103 USA. [Weinman, Steven A.] Univ Kansas, Med Ctr, Dept Internal Med, Kansas City, KS 66103 USA. [Machida, Keigo] Univ So Calif, Keck Sch Med, So Calif Res Ctr ALPD & Cirrhosis, Los Angeles, CA 90033 USA. [Machida, Keigo] Univ So Calif, Keck Sch Med, Dept Mol Microbiol, Los Angeles, CA 90033 USA. [Machida, Keigo] Univ So Calif, Keck Sch Med, Dept Immunol, Los Angeles, CA 90033 USA. [Wang, H. Joe] NIAAA, Div Metab & Hlth Effects HJW, NIH, Bethesda, MD 20892 USA. RP Szabo, G (reprint author), LRB215 Univ Massachusetts, Sch Med, Dept Med, 364 Plantat St, Worcester, MA 01605 USA. EM gyongyi.Szabo@umassmed.edu; wangh4@mail.nih.gov RI Weinman, Steven/E-7012-2011; OI Machida, Keigo/0000-0002-9721-8553; Eken, Ahmet/0000-0002-5816-0686 FU NIH/NIAAA [AA014372, AA-008169, AA-02666, AA017232, AA012863] FX The research reported here was supported by grants from NIH/NIAAA, #AA014372 to GS, #AA-008169 and AA-02666 to JRW, #AA017232 to NAO, and #AA012863 to SAW. NR 135 TC 38 Z9 38 U1 0 U2 8 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD OCT PY 2010 VL 34 IS 10 BP 1675 EP 1686 DI 10.1111/j.1530-0277.2010.01255.x PG 12 WC Substance Abuse SC Substance Abuse GA 656FW UT WOS:000282313600003 PM 20608905 ER PT J AU Hingson, RW AF Hingson, Ralph W. TI Commentary on Nelson, Toomey, Lenk, et al. (2010): "Implementation of NIAAA College Drinking Task Force Recommendations: How Are Colleges Doing 6 Years Later?" SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Editorial Material ID EXCESSIVE ALCOHOL-CONSUMPTION; STUDENT DRINKING; PREVENTION TRIAL; RANDOMIZED-TRIAL; PHYSICIAN ADVICE; INTERVENTIONS; HARMS; IDENTIFICATION; AVAILABILITY; MORTALITY C1 NIAAA, Div Epidemiol & Prevent Res, Bethesda, MD USA. RP Hingson, RW (reprint author), NIAAA, Div Epidemiol & Prevent Res, 5635 Fishers Lane,Room 2077, Bethesda, MD USA. EM rhingson@mail.nih.gov NR 43 TC 3 Z9 3 U1 1 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD OCT PY 2010 VL 34 IS 10 BP 1694 EP 1698 DI 10.1111/j.1530-0277.2010.01315.x PG 5 WC Substance Abuse SC Substance Abuse GA 656FW UT WOS:000282313600005 PM 20860613 ER PT J AU Bousquet, J Schunemann, HJ Zuberbier, T Bachert, C Baena-Cagnani, CE Bousquet, PJ Brozek, J Canonica, GW Casale, TB Demoly, P Gerth van Wijk, R Ohta, K Bateman, ED Calderon, M Cruz, AA Dolen, WK Haughney, J Lockey, RF Lotvall, J O'Byrne, P Spranger, O Togias, A Bonini, S Boulet, LP Camargos, P Carlsen, KH Chavannes, NH Delgado, L Durham, SR Fokkens, WJ Fonseca, J Haahtela, T Kalayci, O Kowalski, ML Larenas-Linnemann, D Li, J Mohammad, Y Mullol, J Naclerio, R O'Hehir, RE Papadopoulos, N Passalacqua, G Rabe, KF Pawankar, R Ryan, D Samolinski, B Simons, FER Valovirta, E Yorgancioglu, A Yusuf, OM Agache, I Ait-Khaled, N Annesi-Maesano, I Beghe, B Ben Kheder, A Blaiss, MS Boakye, DA Bouchard, J Burney, PG Busse, WW Chan-Yeung, M Chen, Y Chuchalin, AG Costa, DJ Custovic, A Dahl, R Denburg, J Douagui, H Emuzyte, R Grouse, L Humbert, M Jackson, C Johnston, SL Kaliner, MA Keith, PK Kim, YY Klossek, JM Kuna, P Le, LT Lemiere, C Lipworth, B Mahboub, B Malo, JL Marshall, GD Mavale-Manuel, S Meltzer, EO Morais-Almeida, M Motala, C Naspitz, C Nekam, K Niggemann, B Nizankowska-Mogilnicka, E Okamoto, Y Orru, MP Ouedraogo, S Palkonen, S Popov, TA Price, D Rosado-Pinto, J Scadding, GK Sooronbaev, TM Stoloff, SW Toskala, E van Cauwenberge, P Vandenplas, O van Weel, C Viegi, G Virchow, JC Wang, DY Wickman, M Williams, D Yawn, BP Zar, HJ Zernotti, M Zhong, N AF Bousquet, J. Schunemann, H. J. Zuberbier, T. Bachert, C. Baena-Cagnani, C. E. Bousquet, P. J. Brozek, J. Canonica, G. W. Casale, T. B. Demoly, P. Gerth van Wijk, R. Ohta, K. Bateman, E. D. Calderon, M. Cruz, A. A. Dolen, W. K. Haughney, J. Lockey, R. F. Lotvall, J. O'Byrne, P. Spranger, O. Togias, A. Bonini, S. Boulet, L. P. Camargos, P. Carlsen, K. H. Chavannes, N. H. Delgado, L. Durham, S. R. Fokkens, W. J. Fonseca, J. Haahtela, T. Kalayci, O. Kowalski, M. L. Larenas-Linnemann, D. Li, J. Mohammad, Y. Mullol, J. Naclerio, R. O'Hehir, R. E. Papadopoulos, N. Passalacqua, G. Rabe, K. F. Pawankar, R. Ryan, D. Samolinski, B. Simons, F. E. R. Valovirta, E. Yorgancioglu, A. Yusuf, O. M. Agache, I. Ait-Khaled, N. Annesi-Maesano, I. Beghe, B. Ben Kheder, A. Blaiss, M. S. Boakye, D. A. Bouchard, J. Burney, P. G. Busse, W. W. Chan-Yeung, M. Chen, Y. Chuchalin, A. G. Costa, D. J. Custovic, A. Dahl, R. Denburg, J. Douagui, H. Emuzyte, R. Grouse, L. Humbert, M. Jackson, C. Johnston, S. L. Kaliner, M. A. Keith, P. K. Kim, Y. Y. Klossek, J. M. Kuna, P. Le, L. T. Lemiere, C. Lipworth, B. Mahboub, B. Malo, J. L. Marshall, G. D. Mavale-Manuel, S. Meltzer, E. O. Morais-Almeida, M. Motala, C. Naspitz, C. Nekam, K. Niggemann, B. Nizankowska-Mogilnicka, E. Okamoto, Y. Orru, M. P. Ouedraogo, S. Palkonen, S. Popov, T. A. Price, D. Rosado-Pinto, J. Scadding, G. K. Sooronbaev, T. M. Stoloff, S. W. Toskala, E. van Cauwenberge, P. Vandenplas, O. van Weel, C. Viegi, G. Virchow, J. C. Wang, D. Y. Wickman, M. Williams, D. Yawn, B. P. Zar, H. J. Zernotti, M. Zhong, N. CA WHO Collaborating Ctr Asthma Rhini TI Development and implementation of guidelines in allergic rhinitis - an ARIA-GA2LEN paper SO ALLERGY LA English DT Article DE ARIA; asthma; EAACI; EFA; GA2LEN; IPCRG; rhinitis ID NONALLERGIC RHINITIS; CONTROLLED-TRIAL; SEVERE ASTHMA; PRIMARY-CARE; RANDOMIZED-TRIALS; CONSORT STATEMENT; GRADING QUALITY; 2008 UPDATE; RECOMMENDATIONS; PREVALENCE AB P>The links between asthma and rhinitis are well characterized. The Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines stress the importance of these links and provide guidance for their prevention and treatment. Despite effective treatments being available, too few patients receive appropriate medical care for both diseases. Most patients with rhinitis and asthma consult primary care physicians and therefore these physicians are encouraged to understand and use ARIA guidelines. Patients should also be informed about these guidelines to raise their awareness of optimal care and increase control of the two related diseases. To apply these guidelines, clinicians and patients need to understand how and why the recommendations were made. The goal of the ARIA guidelines is to provide recommendations about the best management options for most patients in most situations. These recommendations should be based on the best available evidence. Making recommendations requires the assessment of the quality of available evidence, deciding on the balance between benefits and downsides, consideration of patients' values and preferences, and, if applicable, resource implications. Guidelines must be updated as new management options become available or important new evidence emerges. Transparent reporting of guidelines facilitates understanding and acceptance, but implementation strategies need to be improved. C1 [Bousquet, J.] Hop Arnaud Villeneuve, Serv Malad Resp, Univ Hosp, F-34295 Montpellier 5, France. [Bousquet, J.] INSERM, CESP Ctr Res Epidemiol & Populat Hlth, U1018, Villejuif, France. [Schunemann, H. J.; Brozek, J.] McMaster Univ, Dept Clin Epidemiol & Biostat, Hamilton, ON, Canada. [Schunemann, H. J.; Brozek, J.] McMaster Univ, Dept Med, Hamilton, ON, Canada. [Zuberbier, T.] Charite, Allergy Ctr Charite, D-13353 Berlin, Germany. [Bachert, C.; van Cauwenberge, P.] Univ Ghent, B-9000 Ghent, Belgium. [Baena-Cagnani, C. E.; Zernotti, M.] Catholic Univ Cordoba, Fac Med, Cordoba, Argentina. [Baena-Cagnani, C. E.] Univ Genoa, Fac Specializat Resp Med, Genoa, Italy. [Bousquet, P. J.] Univ Nimes Hosp, F-30006 Nimes, France. [Canonica, G. W.; Passalacqua, G.] Univ Genoa, Allergy & Resp Dis Clin, Genoa, Italy. [Casale, T. B.] Creighton Univ, Omaha, NE 68178 USA. [Demoly, P.] Univ Hosp Montpellier, INSERM, U657, Hop Arnaud Villeneuve, Montpellier, France. [Gerth van Wijk, R.] Erasmus MC, Dept Internal Med, Sect Allergol, Rotterdam, Netherlands. [Ohta, K.] Teikyo Univ, Sch Med, Tokyo 173, Japan. [Bateman, E. D.] Univ Cape Town, Fac Hlth Sci, ZA-7925 Cape Town, South Africa. [Calderon, M.] Univ London Imperial Coll Sci Technol & Med, Allergy Unit, London, England. [Cruz, A. A.] Univ Fed Bahia, Fac Med Bahia, Salvador, Brazil. [Cruz, A. A.] CNPq, Salvador, Brazil. [Dolen, W. K.] Med Coll Georgia, Augusta, GA 30912 USA. [Haughney, J.; Ryan, D.; Price, D.] Univ Aberdeen, Aberdeen, Scotland. [Lockey, R. F.] Univ S Florida, Coll Med, Div Allergy & Immunol, Tampa, FL USA. [Lotvall, J.] Univ Gothenburg, Gothenburg, Sweden. [Spranger, O.; Palkonen, S.] EFA European Federat Allergy & Airways Dis Patien, Brussels, Belgium. [Togias, A.] NIAID, Bethesda, MD USA. [Bonini, S.] Univ Naples 2, INMM CNR, Rome, Italy. [Boulet, L. P.; Bouchard, J.] Univ Laval, Laval, PQ, Canada. [Boulet, L. P.] Hop Laval, Inst Cardiol & Pneumol, Laval, PQ, Canada. [Camargos, P.] Univ Fed Minas Gerais, Univ Hosp, Sch Med, Belo Horizonte, MG, Brazil. [Carlsen, K. H.] Ullevaal Univ Hosp, Dept Paediat, Oslo, Norway. [Carlsen, K. H.] Univ Oslo, Fac Med, Oslo, Norway. [Chavannes, N. H.] Leiden Univ, Med Ctr, Dept Publ Hlth & Primary Care, Leiden, Netherlands. [Delgado, L.] Univ Porto, Fac Med, P-4100 Oporto, Portugal. [Durham, S. R.; Burney, P. G.; Johnston, S. L.] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London, England. [Fokkens, W. J.] Univ Amsterdam, Acad Med Ctr, NL-1105 AZ Amsterdam, Netherlands. [Fonseca, J.] Univ Porto, Sch Med, CUF CINTESIS, Hosp S Joao & Inst, P-4100 Oporto, Portugal. [Haahtela, T.] Helsinki Univ Hosp, Skin & Allergy Hosp, Helsinki, Finland. [Kalayci, O.] Hacettepe, Pediat Allergy & Asthma Unit, Ankara, Turkey. [Kowalski, M. L.] Med Univ Lodz, Dept Immunol Rheumatol & Allergy, Lodz, Poland. [Larenas-Linnemann, D.] Hosp Med Sur, Dept Allergy, Mexico City, DF, Mexico. [Li, J.] Guangzhou Med Sch, Affiliated Hosp 1, Guangzhou Inst Resp Dis, Guangzhou, Guangdong, Peoples R China. [Mohammad, Y.] Tishreen Univ, Sch Med, Latakia, Syria. [Mullol, J.] Hosp Clin Univ, IDIBAPS, CIBERES, Barcelona, Catalonia, Spain. [Naclerio, R.] Univ Chicago, Chicago, IL 60637 USA. [O'Hehir, R. E.] Monash Univ, Melbourne, Vic 3004, Australia. [O'Hehir, R. E.] Alfred Hosp, Melbourne, Vic 3004, Australia. [Papadopoulos, N.] Univ Athens, Allergy Res Ctr, Athens, Greece. [Rabe, K. F.] Leiden Univ, Med Ctr, Dept Pulmonol, Leiden, Netherlands. [Pawankar, R.] Nippon Med Sch, Bunkyo Ku, Tokyo 113, Japan. [Ryan, D.] Woodbrook Med Ctr, Loughborough, Leics, England. [Samolinski, B.] Med Univ Warsaw, Warsaw, Poland. [Simons, F. E. R.] Univ Manitoba, Winnipeg, MB, Canada. [Valovirta, E.] Terveystalo Turku, Turku, Finland. [Yorgancioglu, A.] Celal Bayar Univ, Sch Med, Dept Pulmonol, Manisa, Turkey. [Yusuf, O. M.] Allergy & Asthma Inst, Islamabad, Pakistan. [Agache, I.] Transylvania Univ, Brasov, Romania. [Ait-Khaled, N.] The Union, Paris, France. [Annesi-Maesano, I.] INSERM, EPAR, U707, Paris, France. [Annesi-Maesano, I.] UPMC, UMR S, EPAR, Paris, France. [Beghe, B.] Univ Modena & Reggio Emilia, Dept Oncol Haematol & Resp Dis, Modena, Italy. [Ben Kheder, A.] Hop Mami Ariana, Ariana, Tunisia. [Blaiss, M. S.] Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA. [Boakye, D. A.] Univ Ghana, Coll Hlth Sci, Noguchi Mem Inst Med Res, Legon, Accra, Ghana. [Bouchard, J.] Hop Malbaie, Malbaie, PQ, Canada. [Busse, W. W.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA. [Chan-Yeung, M.] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Chen, Y.] Natl Cooperat Grp Pediat Res Asthma, Asthma Clin & Educ Ctr Capital Inst Pediat, Beijing, Peoples R China. [Chuchalin, A. G.] Russian Resp Soc, Moscow, Russia. [Chuchalin, A. G.] Pulmonol Res Inst, Moscow, Russia. [Costa, D. J.] Univ Montpellier, Primary Care Dept, F-34059 Montpellier, France. [Custovic, A.] Univ Manchester, Manchester, Lancs, England. [Dahl, R.] Aarhus Univ Hosp, DK-8000 Aarhus, Denmark. [Denburg, J.] McMaster Univ, AllerGen NCE, Hamilton, ON, Canada. [Douagui, H.] Univ Beni Messous, Ctr Hosp Univ, Algiers, Algeria. [Emuzyte, R.] Vilnius State Univ, Fac Med, Vilnius, Lithuania. [Grouse, L.] Univ Washington, Sch Med, Seattle, WA USA. [Humbert, M.] Univ Paris Sud, Hop Antoine Beclere, Clamart, France. [Jackson, C.] Univ St Andrews, Bute Med Sch, St Andrews, Fife, Scotland. [Kaliner, M. A.] George Washington Univ, Sch Med, Washington, DC USA. [Kaliner, M. A.] Inst Asthma & Allergy, Chevy Chase, MD USA. [Kim, Y. Y.] Seoul Natl Univ Hosp, Seoul 110744, South Korea. [Klossek, J. M.] Univ Poitiers, Poitiers, France. [Kuna, P.] Med Univ Lodz, Barlicki Univ Hosp, Lodz, Poland. [Le, L. T.] Univ Med & Pharm, Ho Chi Minh City, Vietnam. [Lemiere, C.; Malo, J. L.] Univ Montreal, Montreal, PQ, Canada. [Lemiere, C.; Malo, J. L.] Hop Sacre Coeur Montreal, Montreal, PQ, Canada. [Lipworth, B.] Univ Dundee, Dundee, Scotland. [Mahboub, B.] Univ Sharjah, Sharjah, U Arab Emirates. [Marshall, G. D.] Univ Mississippi, Jackson, MS 39216 USA. [Mavale-Manuel, S.] Childrens Hosp, Maputo, Mozambique. [Meltzer, E. O.] Univ Calif San Diego, Allergy & Asthma Med Grp, San Diego, CA 92103 USA. [Meltzer, E. O.] Univ Calif San Diego, Res Ctr, San Diego, CA 92103 USA. [Morais-Almeida, M.] CUF Descobertas Hosp, Immunoallergy Dept, Lisbon, Portugal. [Motala, C.] Red Cross War Mem Childrens Hosp, Cape Town, South Africa. [Motala, C.] UCT, Sch Child & Adolescent Hlth, Cape Town, South Africa. [Naspitz, C.] Univ Fed Sao Paulo, Sao Paulo, Brazil. [Nekam, K.] Hosp Hospitaller Bros Buda, Budapest, Hungary. [Niggemann, B.] German Red Cross Hosp Berlin, Berlin, Germany. [Nizankowska-Mogilnicka, E.] Jagiellonian Univ, Sch Med, Krakow, Poland. [Okamoto, Y.] Chiba Univ, Chiba, Japan. [Popov, T. 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[Williams, D.] Univ N Carolina, Sch Pharm, Chapel Hill, NC USA. [Yawn, B. P.] Univ Minnesota, Olmsted Med Ctr, Rochester, MN USA. [Zar, H. J.] Univ Cape Town, Dept Paediat & Child Hlth, Cape Town, South Africa. RP Bousquet, J (reprint author), Hop Arnaud Villeneuve, Serv Malad Resp, Univ Hosp, 371 Ave Doyen Gaston Giraud, F-34295 Montpellier 5, France. EM jean.bousquet@inserm.fr RI Cruz, Alvaro/I-1676-2012; Delgado, Luis/L-8035-2013; Fonseca, Joao/B-7562-2008; Chavannes, Niels/F-1148-2011; Annesi-Maesano, Isabella/D-9173-2016; van Weel, Chris/D-4375-2009; Johnston, Sebastian/I-2423-2012; O'Hehir, Robyn/H-3627-2011; Dahl, Ronahl/F-8170-2013; jackson, cathy/H-4869-2013; Casale, Thomas/K-4334-2013; Custovic, Adnan/A-2435-2012; FMUP, CINTESIS/C-6631-2014 OI Popov, Todor/0000-0001-5052-5866; Price, David/0000-0002-9728-9992; Cruz, Alvaro/0000-0002-7403-3871; Delgado, Luis/0000-0003-2375-9071; Papadopoulos, Nikolaos/0000-0002-2508-3872; Bousquet, Philippe Jean/0000-0002-0217-5483; Bonini, Sergio/0000-0003-0079-3031; O'Byrne, Paul/0000-0003-0979-281X; Lotvall, Jan/0000-0001-9195-9249; Fonseca, Joao/0000-0002-0887-8796; Chavannes, Niels/0000-0002-8607-9199; van Weel, Chris/0000-0003-3653-4701; O'Hehir, Robyn/0000-0002-3489-7595; Casale, Thomas/0000-0002-3149-7377; Custovic, Adnan/0000-0001-5218-7071; FMUP, CINTESIS/0000-0001-7248-2086 FU EU [FOOD-CT-2004-506378] FX Members of GA2LEN (Global Allergy and Asthma European Network), supported by the Sixth EU Framework program for research, contract no FOOD-CT-2004-506378. NR 60 TC 57 Z9 60 U1 2 U2 25 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0105-4538 EI 1398-9995 J9 ALLERGY JI Allergy PD OCT PY 2010 VL 65 IS 10 BP 1212 EP 1221 DI 10.1111/j.1398-9995.2010.02439.x PG 10 WC Allergy; Immunology SC Allergy; Immunology GA 647PQ UT WOS:000281631500002 PM 20887423 ER PT J AU Ferrari, R Kapogiannis, D Huey, ED Grafman, J Hardy, J Momeni, P AF Ferrari, Raffaele Kapogiannis, Dimitrios Huey, Edward D. Grafman, Jordan Hardy, John Momeni, Parastoo TI Novel Missense Mutation in Charged Multivesicular Body Protein 2B in a Patient With Frontotemporal Dementia SO ALZHEIMER DISEASE & ASSOCIATED DISORDERS LA English DT Article DE dementia; FTD; CHMP2B; gene; missense mutation ID LOBAR DEGENERATION; ESCRT-III; NEURODEGENERATIVE DISEASE; CHMP2B MUTATIONS; CHROMOSOME-3; AUTOPHAGY; CONSENSUS; COMPLEX; FTD-3; MICE AB Frontotemporal dementia (FTD) is the second major cause of dementia in persons below the age of 65 years after Alzheimer disease. FTD is clinically, pathologically, and genetically heterogeneous and has been associated with mutations in different genes located on chromosomes 17, 9, and 3. In our study we report a novel heterozygous g. 26218G > A variant in exon 6 of charged multivesicular body protein 2B (CHMP2B), predicted to cause the amino acid change p.Ser187Asn, in one patient diagnosed with FTD. We were not able to determine the mode of inheritance of the mutation as we did not have access to the genetically informative family members of the proband; those who were screened did not carry the variant. We did not find this variant in 273 White controls although we did find it in 6 of 94 African-American controls. Most of the mutations in CHMP2B which are considered pathogenic lead to partial deletion of the C-terminus region of CHMP2B protein. Based on previous reports and on our current data, missense mutations in this gene seem unlikely to be pathogenic. The pathogenicity of CHMP2B mutations requires further investigation. C1 [Ferrari, Raffaele; Momeni, Parastoo] Texas Tech Univ, Hlth Sci Ctr, Dept Internal Med, Lubbock, TX 79430 USA. [Momeni, Parastoo] Texas Tech Univ, Hlth Sci Ctr, Dept Pharmacol & Neurosci, Lubbock, TX 79430 USA. [Grafman, Jordan] Natl Inst Neurol Disorders & Stroke Bldg, Cognit Neurosci Sect, Bethesda, MD USA. [Hardy, John] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Kapogiannis, Dimitrios; Huey, Edward D.] NIA, NIH, Clin Res Branch, Baltimore, MD 21224 USA. [Huey, Edward D.] Isl Jewish Healthcare Syst, N Shore Long, Litwin Zucker Ctr Res Alzheimers Dis & Memory Dis, Manhasset, NY USA. [Ferrari, Raffaele; Hardy, John] UCL, Inst Neurol, Dept Mol Neurosci, London, England. [Ferrari, Raffaele; Hardy, John] UCL, Inst Neurol, Reta Lila Weston Labs, London, England. RP Momeni, P (reprint author), Texas Tech Univ, Hlth Sci Ctr, Dept Internal Med, 3601 4th St STOP 9410, Lubbock, TX 79430 USA. EM parastoo.momeni@ttuhsc.edu RI Hardy, John/C-2451-2009; OI Grafman, Jordan H./0000-0001-8645-4457 FU South Plains Foundation; National Institutes of Health (NIH)/The National Institute on Aging (NIA)/The National Institute of Neurological Disorders and Stroke (NINDS); NINDS [1K99NS060766-01]; Litwin-Zucker Center for Research on Alzheimer's Disease and Memory Disorders FX Parastoo Momeni molecular genetics work is funded by the office of the Dean of the School of Medicine, Department of Internal Medicine, at Texas Tech Health Sciences Center and a grant from South Plains Foundation. This study was supported by the intramural programs of The National Institutes of Health (NIH)/The National Institute on Aging (NIA)/The National Institute of Neurological Disorders and Stroke (NINDS; J.G. and E. D. H.), NINDS grant 1K99NS060766-01 (E. D. H.), and the Litwin-Zucker Center for Research on Alzheimer's Disease and Memory Disorders (E. D. H. and P.D.). NR 37 TC 3 Z9 3 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-0341 J9 ALZ DIS ASSOC DIS JI Alzheimer Dis. Assoc. Dis. PD OCT-DEC PY 2010 VL 24 IS 4 BP 397 EP 401 DI 10.1097/WAD.0b013e3181df20c7 PG 5 WC Clinical Neurology; Pathology SC Neurosciences & Neurology; Pathology GA 681JN UT WOS:000284308100014 PM 20592581 ER PT J AU Kong, MH Peterson, ED Fonarow, GC Sanders, GD Yancy, CW Russo, AM Curtis, AB Sears, SF Thomas, KL Campbell, S Carlson, MD Chiames, C Cook, NL Hayes, DL LaRue, M Hernandez, AF Lyons, EL Al-Khatib, SM AF Kong, Melissa H. Peterson, Eric D. Fonarow, Gregg C. Sanders, Gillian D. Yancy, Clyde W. Russo, Andrea M. Curtis, Anne B. Sears, Samuel F., Jr. Thomas, Kevin L. Campbell, Susan Carlson, Mark D. Chiames, Chris Cook, Nakela L. Hayes, David L. LaRue, Michelle Hernandez, Adrian F. Lyons, Edward L. Al-Khatib, Sana M. TI Addressing disparities in sudden cardiac arrest care and the underutilization of effective therapies SO AMERICAN HEART JOURNAL LA English DT Article ID IMPLANTABLE-CARDIOVERTER-DEFIBRILLATORS; CONGESTIVE-HEART-FAILURE; LEFT-VENTRICULAR DYSFUNCTION; QUALITY-OF-CARE; MYOCARDIAL-INFARCTION; RACIAL-DIFFERENCES; UNITED-STATES; IMPROVE HF; EJECTION FRACTION; RANDOMIZED-TRIAL AB Sudden cardiac arrest (SCA) is the most common cause of death in the Unites States. Despite its major impact on public health, significant challenges exist at the patient, provider, public, and policy levels with respect to raising more widespread awareness and understanding of SCA risks, identifying patients at risk for SCA, addressing barriers to SCA care, and eliminating disparities in SCA care and outcomes. To address many of these challenges, the Duke Center for the Prevention of Sudden Cardiac Death at the Duke Clinical Research Institute (Durham, NC) held a think tank meeting on December 7, 2009, convening experts on this issue from clinical cardiology, cardiac electrophysiology, health policy and economics, the US Food and Drug Administration, the Centers for Medicare and Medicaid Services, the Agency for Health Care Research and Quality, and device and pharmaceutical manufacturers. The specific goals of the meeting were to examine existing educational tools on SCA for patients, health care providers, and the public and explore ways to enhance and disseminate these tools; to propose a framework for improved identification of patients at risk of SCA; and to review the latest data on disparities in SCA care and explore ways to reduce these disparities. This article summarizes the discussions that occurred at the meeting. (Am Heart J 2010; 160: 605-618.e1.) C1 [Kong, Melissa H.; Peterson, Eric D.; Sanders, Gillian D.; Thomas, Kevin L.; Hernandez, Adrian F.; Al-Khatib, Sana M.] Duke Univ, Med Ctr, Div Cardiol, Durham, NC 27710 USA. [Kong, Melissa H.; Peterson, Eric D.; Sanders, Gillian D.; Thomas, Kevin L.; Hernandez, Adrian F.; Al-Khatib, Sana M.] Duke Clin Res Inst, Durham, NC USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, Ahmanson UCLA Cardiomyopathy Ctr, Los Angeles, CA USA. [Yancy, Clyde W.] Baylor Univ, Baylor Heart & Vasc Inst, Dallas, TX USA. [Russo, Andrea M.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Cooper Univ Hosp, Camden, NJ 08103 USA. [Curtis, Anne B.] Univ S Florida, Tampa, FL USA. [Sears, Samuel F., Jr.] E Carolina Univ, Dept Psychol & Cardiovasc Sci, Greenville, NC USA. [Campbell, Susan] WomenHeart Natl Coalit Women Heart Dis, Washington, DC USA. [Carlson, Mark D.] St Jude Med, St Paul, MN USA. [Chiames, Chris] Sudden Cardiac Arrest Assoc, Washington, DC USA. [Cook, Nakela L.] NHLBI, NIH, Bethesda, MD 20892 USA. [Hayes, David L.] Mayo Clin, Div Cardiovasc Dis, Rochester, MN USA. [LaRue, Michelle] Natl Alliance Hispan Hlth, Washington, DC USA. [Lyons, Edward L.] GE Healthcare, Princeton, PA USA. RP Kong, MH (reprint author), Duke Univ, Med Ctr, Div Cardiol, DUMC Box 31294, Durham, NC 27710 USA. EM kong0017@mc.duke.edu RI Hernandez, Adrian F./A-7818-2016 OI sears, samuel/0000-0002-7863-3591; Hernandez, Adrian F./0000-0003-3387-9616 FU Medtronic; Biotronik; NHLBI; Agency of Healthcare Research and Quality; St Jude Medical; Sanofi-Aventis; Biosense Webster; Johnson Johnson; Amylin; Merck Co; NIH [5-T32-DK-007731-15]; Bristol Myers Squibb; Lilly; Boston Scientific FX Sana M. Al-Khatib: receives research funding and speaking fees from Medtronic and Biotronik. She also receives research funding from the NHLBI and from the Agency of Healthcare Research and Quality.; Susan Campbell: none.; Mark Carlson: none.; Chris Chiames: none.; Nakela L. Cook: the views expressed in this paper do not necessarily reflect the views or official positions of the NHLBI, the National Institutes of Health (NIH), or the Department of Health and Human Services (DHHS).; Anne B. Curtis: receives research funding from Medtronic and St Jude Medical and consulting, speakers' bureau, and/or fellowship support from Medtronic, St Jude Medical, Biotronik, Sanofi-Aventis, and Biosense Webster.; Gregg C. Fonarow: receives research funding from NHLBI; serves as a consultant for Novartis, Medtronic, and St Jude Medical; and receives honoraria from GlaxoSmithKline, St Jude Medical, and Medtronic.; David L. Hayes: serves on an advisory board for St Jude Medical, Boston Scientific, and Pixel Velocity and receives honoraria for speaking from St Jude Medical, Boston Scientific, Medtronic, Sorin Medical, Biotronik, and Blackwell-Futura.; Adrian F. Hernandez: receives research support from Johnson & Johnson, Amylin, and Merck & Co and receives honoraria from Amgen, AstraZeneca, and Medtronic.; Melissa H. Kong: receives research funding from Biotronik and was supported by a Ruth L. Kirschstein-National Research Service Award NIH (grant 5-T32-DK-007731-15). The contents of this work are solely the responsibility of the authors and do not necessarily represent the official views of the NIH.; Edward L. Lyons: none.; Eric D. Peterson: receives research funding from Bristol Myers Squibb, Sanofi-Aventis, Merck, Lilly, and Johnson & Johnson.; Andrea M. Russo: receives research funding from Medtronic, Boston Scientific, and Biotronik and honoraria from Medtronic, Boston Scientific, and St Jude Medical.; Gillian D. Sanders: receives research funding from Medtronic.; Samuel F. Sears, Jr.: receives research funding from Medtronic and St Jude Medical and honoraria from Medtronic, Boston Scientific, St Jude Medical, and Biotronik and serves as a consultant to Medtronic.; Kevin L. Thomas: receives research funding from Medtronic and honoraria from St Jude Medical and serves on an advisory board for Medtronic and Boston Scientific.; Clyde W. Yancy: none. NR 54 TC 8 Z9 8 U1 0 U2 6 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD OCT PY 2010 VL 160 IS 4 BP 605 EP U240 DI 10.1016/j.ahj.2010.07.011 PG 15 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 660WN UT WOS:000282677300009 PM 20934553 ER PT J AU Carson, P Fiuzat, M O'Connor, C Anand, I Plehn, J Lindenfeld, JA Silver, M White, M Miller, A Davis, G Robertson, AD Bristow, M Gottlieb, S AF Carson, Peter Fiuzat, Mona O'Connor, Christopher Anand, Inder Plehn, Jonathan Lindenfeld, Jo Ann Silver, Marc White, Michel Miller, Alan Davis, Gordon Robertson, Alastair D. Bristow, Michael Gottlieb, Stephen TI Determination of hospitalization type by investigator case report form or adjudication committee in a large heart failure clinical trial (beta-Blocker Evaluation of Survival Trial [BEST]) SO AMERICAN HEART JOURNAL LA English DT Article ID INFARCTION END-POINTS; MYOCARDIAL-INFARCTION; EVENTS COMMITTEE; DEATH; MODE; BUCINDOLOL; MORBIDITY; OUTCOMES; THERAPY; IMPACT AB Background End point committees are routinely used to adjudicate efficacy and safety end points in clinical trials. The 2,708-patient beta-Blocker Evaluation of Survival Trial (BEST) originally determined hospitalization type via investigator case report forms (CRFs), which captured whether a hospitalization was due to worsening heart failure (HF). Recently, the BEST End Points Committee (EPC) completed a blinded adjudication of all hospitalizations, allowing a comparison of the CRF method to the EPC method of determining hospitalization type. We sought to compare the investigator-determined mode of hospitalizations with the adjudicated events, to quantify the degree of agreement, and to compare the clinical trial results by method of event classification. Methods The BEST EPC reviewed all 5,086 hospitalizations that occurred in BEST. Events were identified using investigator-reported hospitalizations, as well as those documented by FDA Form 3500 (MedWatch) reports. Results The investigators identified more HF hospitalization events than adjudication (2,466 vs 1,729, P < .0001, paired analysis). Eight hundred thirty-four (34%) HF hospitalizations identified in CRFs were not confirmed by adjudication. Ninety-seven (6%) adjudicated events were not identified by the investigator reported method. One thousand six hundred thirty-two events were similarly identified by both methods. Conclusions The EPC adjudication identified fewer HF hospitalizations than did the investigator reported method with no change in the hazard ratio for this end point. Our findings suggest that independent end point committees may improve reliability through reduced variance, thus providing similar outcome results with fewer events and no increase in CIs. (Am Heart J 2010; 160: 649-54.) C1 [Fiuzat, Mona] Duke Univ, Med Ctr, Div Clin Pharmacol, Durham, NC 27710 USA. [Carson, Peter] Dept Vet Affairs, Washington, DC USA. [Fiuzat, Mona; Davis, Gordon; Bristow, Michael] ARCA Biopharma, Broomfield, CO USA. [Anand, Inder] Dept Vet Affairs, Minneapolis, MN USA. [Plehn, Jonathan] NHLBI, Washington, DC USA. [Lindenfeld, Jo Ann; Robertson, Alastair D.; Bristow, Michael] Univ Colorado, Hlth Sci Ctr, Denver, CO USA. [Silver, Marc] Advocate Christ Med Ctr, Oak Lawn, IL USA. [White, Michel] Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada. [Miller, Alan] Univ Florida, Hlth Sci Ctr, Jacksonville, FL 32209 USA. [Gottlieb, Stephen] Univ Maryland, Baltimore, MD 21201 USA. RP Fiuzat, M (reprint author), Duke Univ, Med Ctr, Div Clin Pharmacol, Durham, NC 27710 USA. EM mona.fiuzat@duke.edu RI bristow, michael/G-7850-2011 NR 17 TC 11 Z9 11 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD OCT PY 2010 VL 160 IS 4 BP 649 EP 654 DI 10.1016/j.ahj.2010.07.004 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 660WN UT WOS:000282677300014 PM 20934558 ER PT J AU Khan, AM Sullivan, L McCabe, E Levy, D Vasan, RS Wang, TJ AF Khan, Abigail May Sullivan, Lisa McCabe, Elizabeth Levy, Daniel Vasan, Ramachandran S. Wang, Thomas J. TI Lack of association between serum magnesium and the risks of hypertension and cardiovascular disease SO AMERICAN HEART JOURNAL LA English DT Article ID CORONARY-HEART-DISEASE; BLOOD-PRESSURE; DIETARY MAGNESIUM; ATHEROSCLEROSIS-RISK; NUTRITIONAL FACTORS; INCIDENT HYPERTENSION; INSULIN-RESISTANCE; NATIONAL SAMPLE; ARTERY-DISEASE; DOUBLE-BLIND AB Background Experimental studies have linked hypomagnesemia with the development of vascular dysfunction, hypertension, and atherosclerosis. Prior clinical studies have yielded conflicting results but were limited by the use of self-reported magnesium intake or short follow-up periods. Methods We examined the relationship between serum magnesium concentration and incident hypertension, cardiovascular disease (CVD), and mortality in 3,531 middle-aged adult participants in the Framingham Heart Study offspring cohort. Analyses were performed using Cox proportional hazards regressions, adjusted for traditional CVD risk factors. Results Follow-up was 8 years for new-onset hypertension (551 events) and 20 years for CVD (554 events). There was no association between baseline serum magnesium and the development of hypertension (multivariable-adjusted hazards ratio per 0.15 mg/dL 1.03, 95% CI 0.92-1.15, P = .61), CVD (0.83, 95% CI 0.49-1.40, P = .49), or all-cause mortality (0.77, 95% CI 0.41-1.45, P = .42). Similar findings were observed in categorical analyses, in which serum magnesium was modeled in categories (<1.5, 1.5-2.2, >2.2 mg/dL) or in quartiles. Conclusions In conclusion, data from this large, community-based cohort do not support the hypothesis that low serum magnesium is a risk factor for developing hypertension or CVD. (Am Heart J 2010; 160: 715-20.) C1 [Khan, Abigail May; McCabe, Elizabeth; Wang, Thomas J.] Harvard Univ, Massachusetts Gen Hosp, Div Cardiol, Dept Med,Med Sch, Boston, MA 02114 USA. [Sullivan, Lisa; Levy, Daniel; Vasan, Ramachandran S.; Wang, Thomas J.] Framingham Heart Dis Epidemiol Study, Framingham, MA USA. [Sullivan, Lisa] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Levy, Daniel; Vasan, Ramachandran S.] Boston Med Ctr, Epidemiol Sect, Boston, MA USA. [Levy, Daniel; Vasan, Ramachandran S.] Boston Med Ctr, Sect Prevent Med, Boston, MA USA. [Levy, Daniel] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA. [Vasan, Ramachandran S.] Boston Med Ctr, Cardiol Sect, Boston, MA USA. RP Wang, TJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Div Cardiol, Dept Med,Med Sch, GRB 800,55 Fruit St, Boston, MA 02114 USA. EM tjwang@partners.org OI Ramachandran, Vasan/0000-0001-7357-5970; Sullivan, Lisa/0000-0003-0726-7149 FU NHLBI NIH HHS [K24 HL004334, N01 HC025195, N01HC25195, R01 HL086875] NR 50 TC 29 Z9 30 U1 0 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD OCT PY 2010 VL 160 IS 4 BP 715 EP 720 DI 10.1016/j.ahj.2010.06.036 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 660WN UT WOS:000282677300022 PM 20934566 ER PT J AU Shomaker, LB Tanofsky-Kraff, M Zocca, JM Courville, A Kozlosky, M Columbo, KM Wolkoff, LE Brady, SM Crocker, MK Ali, AH Yanovski, SZ Yanovski, JA AF Shomaker, Lauren B. Tanofsky-Kraff, Marian Zocca, Jaclyn M. Courville, Amber Kozlosky, Merel Columbo, Kelli M. Wolkoff, Laura E. Brady, Sheila M. Crocker, Melissa K. Ali, Asem H. Yanovski, Susan Z. Yanovski, Jack A. TI Eating in the absence of hunger in adolescents: intake after a large-array meal compared with that after a standardized meal SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article ID SENSORY-SPECIFIC SATIETY; ENERGY-INTAKE; HISPANIC CHILDREN; AFRICAN-AMERICAN; PUBERTAL CHANGES; PORTION SIZE; FOOD; OVERWEIGHT; BEHAVIOR; GIRLS AB Background: Eating in the absence of hunger (EAH) is typically assessed by measuring youths' intake of palatable snack foods after a standard meal designed to reduce hunger. Because energy intake required to reach satiety varies among individuals, a standard meal may not ensure the absence of hunger among participants of all weight strata. Objective: The objective of this study was to compare adolescents' EAH observed after access to a very large food array with EAH observed after a standardized meal. Design: Seventy-eight adolescents participated in a randomized crossover study during which EAH was measured as intake of palatable snacks after ad libitum access to a very large array of lunch-type foods (>10,000 kcal) and after a lunch meal standardized to provide 50% of the daily estimated energy requirements. Results: The adolescents consumed more energy and reported less hunger after the large-array meal than after the standardized meal (P values < 0.001). They consumed approximate to 70 kcal less EAH after the large-array meal than after the standardized meal (295 +/- 18 compared with 365 +/- 20 kcal; P < 0.001), but EAH intakes after the large-array meal and after the standardized meal were positively correlated (P values < 0.001). The body mass index z score and overweight were positively associated with EAH in both paradigms after age, sex, race, pubertal stage, and meal intake were controlled for (P values <= 0.05). Conclusion: EAH is observable and positively related to body weight regardless of whether youth eat in the absence of hunger from a very large-array meal or from a standardized meal. This trial was registered at clinicaltrials.gov as NCT00631644. Am J Clin Nutr 2010;92:697-703. C1 [Shomaker, Lauren B.; Tanofsky-Kraff, Marian; Columbo, Kelli M.; Wolkoff, Laura E.] Uniformed Serv Univ Hlth Sci, Dept Med & Clin Psychol, Bethesda, MD 20814 USA. [Shomaker, Lauren B.; Tanofsky-Kraff, Marian; Zocca, Jaclyn M.; Columbo, Kelli M.; Wolkoff, Laura E.; Brady, Sheila M.; Crocker, Melissa K.; Ali, Asem H.; Yanovski, Susan Z.; Yanovski, Jack A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Unit Growth & Obes, Program Dev Endocrinol & Genet, NIH, Bethesda, MD USA. [Courville, Amber; Kozlosky, Merel] NIH, Dept Nutr, Ctr Clin, Bethesda, MD 20892 USA. [Ali, Asem H.; Yanovski, Susan Z.] NIDDKD, Div Digest Dis & Nutr, NIH, Bethesda, MD 20892 USA. RP Shomaker, LB (reprint author), Uniformed Serv Univ Hlth Sci, Dept Med & Clin Psychol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM shomakel@mail.nih.gov RI Kauk, Rachel/H-3622-2012; OI Yanovski, Jack/0000-0001-8542-1637 FU National Institute of Child Health and Human Development [IF32HD056762, Z01-HD-00641]; National Institute of Diabetes and Digestive and Kidney Diseases [IR01DK080906]; Uniformed Services University of the Health Sciences [R072IC]; National Center on Minority Health and Health Disparities; Office of Behavioral and Social Sciences Research FX Supported by National Research Service Award IF32HD056762 from the National Institute of Child Health and Human Development (to LBS), National Institute of Diabetes and Digestive and Kidney Diseases grant IR01DK080906 and Uniformed Services University of the Health Sciences grant R072IC (to MT-K), and Intramural Research Program grant Z01-HD-00641 from the National Institute of Child Health and Human Development with supplemental funding from the National Center on Minority Health and Health Disparities and the Office of Behavioral and Social Sciences Research (to JAY). NR 33 TC 37 Z9 37 U1 1 U2 8 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD OCT PY 2010 VL 92 IS 4 BP 697 EP 703 DI 10.3945/ajcn.2010.29812 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 655FU UT WOS:000282234100005 PM 20720255 ER PT J AU Furtado, JD Campos, H Sumner, AE Appel, LJ Carey, VJ Sacks, FM AF Furtado, Jeremy D. Campos, Hannia Sumner, Anne E. Appel, Lawrence J. Carey, Vincent J. Sacks, Frank M. TI Dietary interventions that lower lipoproteins containing apolipoprotein C-III are more effective in whites than in blacks: results of the OmniHeart trial SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article ID CORONARY-HEART-DISEASE; TRIGLYCERIDE-RICH LIPOPROTEINS; CARDIOVASCULAR RISK-FACTORS; INSULIN-RESISTANCE; ENDOTHELIAL-CELLS; ETHNIC-DIFFERENCES; AFRICAN-AMERICANS; TRANSGENIC MICE; MONOCYTIC CELLS; BLOOD-PRESSURE AB Background: Blacks have lower average triglyceride and LDL cholesterol concentrations than do whites but higher rates of coronary heart disease. Apolipoprotein (apo) C-III in VLDL and LDL stimulates atherogenie processes in vascular cells. In blacks, the concentration of lipoproteins with apo C-III is unknown, and the response to dietary strategies that lower triglyceride and apo C-III has not been investigated Objective: We compared the concentration of and dietary effects on apo C-III containing lipoproteins in blacks and whites. Design: In a randomized, 3-period feeding study [OmniHeart (Optimal Macronutrient Intake Trial to Prevent Heart Disease)] we measured lipoprotein concentrations in 89 blacks and 73 whites who consumed self-selected diets (baseline) and after 3 healthful diets emphasizing carbohydrate, unsaturated fat, or protein. Participants had prehypertension or hypertension, and 79% were overweight or obese. Results: While consuming self-selected diets, blacks had lower apo C-III in total plasma, VLDL, and LDL than did whites. Unsaturated fat and protein diets lowered plasma apo C-III (16% and 18%, respectively) and triglyceride (12% and 21%, respectively) in whites but not in blacks, reducing racial differences. Most important, blacks had a lower concentration of atherogenic LDL with apo C-III at baseline and after study diets (34-41% lower, P < 0.02). The molar ratio of apo E to apo B was higher in blacks than in whites in total plasma and LDL at baseline and after the study diets. Conclusions: Blacks have lower concentrations of atherogenic lipoproteins that contain apo C-III than do whites when consuming diverse diets and an attenuated dietary response of triglyceride and apo C-III. Dietary efforts to lower triglyceride and apo C-III may be more effective in whites than in blacks. The OmniHeart Trial was registered at www.clinicaltrials.gov as NCT00051350. Am J Clin Nutr 2010;92:714-22. C1 [Furtado, Jeremy D.; Campos, Hannia; Sacks, Frank M.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Appel, Lawrence J.] Johns Hopkins Med Inst, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD 21205 USA. [Sumner, Anne E.] NIDDKD, NIH, Bethesda, MD USA. [Carey, Vincent J.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. RP Furtado, JD (reprint author), 665 Huntington Ave,Bldg 1,Room 202, Boston, MA 02115 USA. EM jfurtado@hsph.harvard.edu FU National Institutes of Health [HL67098, DK63214, HL68712, RR02635]; NIDDK (Bethesda, MD) FX Funding for this study was provided through grants HL67098, DK63214, HL68712, and RR02635 from the National Institutes of Health. The following companies donated food: The Almond Board, International Tree Nut Council, Olivio Premium Products Inc, and The Peanut Institute. AES was supported by the intramural program of NIDDK (Bethesda, MD). NR 40 TC 9 Z9 10 U1 0 U2 3 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD OCT PY 2010 VL 92 IS 4 BP 714 EP 722 DI 10.3945/ajcn.2009.28532 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 655FU UT WOS:000282234100007 PM 20826623 ER PT J AU Kant, AK Graubard, BI AF Kant, Ashima K. Graubard, Barry I. TI Contributors of water intake in US children and adolescents: associations with dietary and meal characteristics-National Health and Nutrition Examination Survey 2005-2006 SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article ID SUGAR-SWEETENED BEVERAGES; BODY-MASS INDEX; GERMAN CHILDREN; NUTRIENT INTAKE; DRINKING-WATER; FLUID INTAKE; CONSUMPTION; WEIGHT; PROVISION; PATTERNS AB Background: Little is known about the association of contributors of total water intake with dietary characteristics in US children. Objective: We examined intakes of total water and its contributors and their associations with diet and meal reporting in children and adolescents. Design: Dietary data for children 2-19 y of age (n = 3978) from the National Health and Nutrition Examination Survey 2005-2006 were used to compute usual intake of total water. The association of total water and its contributors with sociodemographic characteristics and dietary and meal attributes was examined by using multiple regression analysis. Results: The adjusted mean intakes of total water in Americans aged 2-5, 6-11, and 12-19 y were 1.4, 1.6, and 2.4 L, respectively. The mean usual intake of total water was generally less than the Adequate Intake; overall, more boys reported intakes of at least the Adequate Intake. The percentage of total water intake from plain water increased with age. Plain water intake was inversely associated with the intake of beverage moisture and the energy density of foods; conversely, beverage moisture was positively associated with dietary energy, fat, and the energy density of foods. Associations of water contributors with meal patterns (number of eating occasions, reporting of breakfast or snack) were inconsistent across age groups. Nearly 80% of food moisture, >66% of beverage moisture, and approximate to 30%] of plain water were reported with main meals. Conclusions: Intake of total water over 24 h from different contributors varied by age. Qualitative differences in dietary intake in association with the amount of plain water and beverage moisture in the recalls were observed. American children and adolescents consumed more than two-thirds of their daily beverages with main meals. Am J Clin Nutr 2010;92:887-96. C1 [Kant, Ashima K.] CUNY Queens Coll, Dept Family Nutr & Exercise Sci, Flushing, NY 11367 USA. [Graubard, Barry I.] NCI, Div Canc Epidemiol & Genet, Biostat Branch, NIH, Bethesda, MD 20892 USA. RP Kant, AK (reprint author), CUNY Queens Coll, Dept Family Nutr & Exercise Sci, Remsen Hall,Room 306E, Flushing, NY 11367 USA. EM ashima.kant@qc.cuny.edu FU Department of Health and Human Services, National Cancer Institute, NIH FX Supported in part by the intramural research program of the Department of Health and Human Services, National Cancer Institute, NIH (to BIG). NR 38 TC 56 Z9 61 U1 0 U2 7 PU AMER SOC NUTRITION-ASN PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0002-9165 EI 1938-3207 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD OCT PY 2010 VL 92 IS 4 BP 887 EP 896 DI 10.3945/ajcn.2010.29708 PG 10 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 655FU UT WOS:000282234100028 PM 20685949 ER PT J AU Lai, JP Sandhu, DS Moser, CD Sanderson, S Roberts, LR AF Lai, Jinping Sandhu, Dalbir S. Moser, Catherine D. Sanderson, Schuyler Roberts, Lewis R. TI Sulfatase 2 (SULF2) Protects Hepatocellular Carcinoma Cells Against Apoptosis Induced by PI3K Inhibitor LY294002 SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Clinical-Pathology CY OCT 27-31, 2010 CL San Francisco, CA SP Amer Soc Clin Pathol C1 [Lai, Jinping] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. [Sandhu, Dalbir S.; Moser, Catherine D.; Roberts, Lewis R.] Mayo Clin, Div Gastroenterol & Hepatol, Rochester, MN USA. [Sanderson, Schuyler] Mayo Clin, Dept Pathol, Rochester, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD OCT PY 2010 VL 134 IS 4 MA 49 BP 677 EP 677 PG 1 WC Pathology SC Pathology GA 652NN UT WOS:000282013900065 ER PT J AU Watters, JL Park, Y Hollenbeck, A Schatzkin, A Albanes, D AF Watters, Joanne L. Park, Yikyung Hollenbeck, Albert Schatzkin, Arthur Albanes, Demetrius TI Alcoholic Beverages and Prostate Cancer in a Prospective US Cohort Study SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE alcoholic beverages; prostatic neoplasms ID RED WINE CONSUMPTION; CIGARETTE-SMOKING; PHYSICAL-ACTIVITY; HORMONE LEVELS; RISK; MEN; METAANALYSIS; HEALTH; ASSOCIATION; DRINKING AB Despite numerous investigations, the correlation between alcohol consumption and prostate cancer risk remains uncertain. This report investigated the association between alcohol use and prostate cancer risk in a prospective cohort study of 294,707 US men aged 50-71 years in 1995-1996. Cox proportional hazards regression models with hazard ratios and 95% confidence intervals were adjusted for characteristics including age, race, body mass index, physical activity, and family history of prostate cancer, as well as testing for prostate-specific antigen and a digital rectal examination. There were 15,327 nonadvanced and 1,900 advanced prostate cancers identified through 2003 and 514 fatal cases through 2005. Risk of nonadvanced prostate cancer was 25% higher for men consuming >= 6 drinks daily (hazard ratio = 1.25, 95% confidence interval: 1.13, 1.37), 19% higher for men consuming 3-<6 drinks daily, and 6% higher for men consuming up to 3 drinks daily, compared with nondrinkers. The association between alcohol consumption and nonadvanced prostate cancer risk did not differ appreciably by age, family history of prostate cancer, smoking status, body mass index, or self-reported prostate-specific antigen testing and digital rectal examination (the latter available for >60% of respondents). The authors observed no association between alcohol intake and advanced prostate cancer and an inverse association with fatal prostate cancer among heavy drinkers. These findings suggest that higher alcohol consumption modestly increases nonadvanced prostate cancer risk. C1 [Watters, Joanne L.; Park, Yikyung; Schatzkin, Arthur; Albanes, Demetrius] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Hollenbeck, Albert] AARP, Washington, DC USA. RP Watters, JL (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, 6120 Execut Blvd,EPS Suite 320, Bethesda, MD 20892 USA. EM wattersj@mail.nih.gov RI Albanes, Demetrius/B-9749-2015; OI Park, Yikyung/0000-0002-6281-489X FU National Cancer Institute, National Institutes of Health, Bethesda, Maryland FX The study was funded by the Intramural Research Program of the National Cancer Institute, National Institutes of Health, Bethesda, Maryland. NR 31 TC 16 Z9 16 U1 0 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD OCT 1 PY 2010 VL 172 IS 7 BP 773 EP 780 DI 10.1093/aje/kwq200 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 654KJ UT WOS:000282166900006 PM 20813803 ER PT J AU Friesen, MC Demers, PA Spinelli, JJ Eisen, EA Lorenzi, MF Le, ND AF Friesen, Melissa C. Demers, Paul A. Spinelli, John J. Eisen, Ellen A. Lorenzi, Maria F. Le, Nhu D. TI Chronic and Acute Effects of Coal Tar Pitch Exposure and Cardiopulmonary Mortality Among Aluminum Smelter Workers SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE air pollutants; cohort studies; heart diseases; occupational diseases; polycyclic hydrocarbons, aromatic ID POLYCYCLIC AROMATIC-HYDROCARBONS; REDUCTION PLANT WORKERS; ISCHEMIC-HEART-DISEASE; PARTICULATE AIR-POLLUTION; OCCUPATIONAL-EXPOSURE; MYOCARDIAL-INFARCTION; CANCER EXPERIENCE; ASPHALT WORKERS; JANUARY 1; NOISE AB Air pollution causes several adverse cardiovascular and respiratory effects. In occupational studies, where levels of particulate matter and polycyclic aromatic hydrocarbons (PAHs) are higher, the evidence is inconsistent. The effects of acute and chronic PAH exposure on cardiopulmonary mortality were examined within a Kitimat, Canada, aluminum smelter cohort (n = 7,026) linked to a national mortality database (1957-1999). No standardized mortality ratio was significantly elevated compared with the province's population. Smoking-adjusted internal comparisons were conducted using Cox regression for male subjects (n = 6,423). Ischemic heart disease (IHD) mortality (n = 281) was associated with cumulative benzo[a]pyrene (B(a)P) exposure (hazard ratio = 1.62, 95% confidence interval: 1.06, 2.46) in the highest category. A monotonic but nonsignificant trend was observed with chronic B(a)P exposure and acute myocardial infarction (n = 184). When follow-up was restricted to active employment, the hazard ratio for IHD was 2.39 (95% confidence interval: 0.95, 6.05) in the highest cumulative B(a)P category. The stronger associations observed during employment suggest that risk may not persist after exposure cessation. No associations with recent or current exposure were observed. IHD was associated with chronic (but not current) PAH exposure in a high-exposure occupational setting. Given the widespread workplace exposure to PAHs and heart disease's high prevalence, even modest associations produce a high burden. C1 [Friesen, Melissa C.; Eisen, Ellen A.] Univ Calif Berkeley, Sch Publ Hlth, Environm Hlth Sci Div, Berkeley, CA 94720 USA. [Demers, Paul A.] Univ British Columbia, Sch Environm Hlth, Vancouver, BC V5Z 1M9, Canada. [Spinelli, John J.; Lorenzi, Maria F.; Le, Nhu D.] British Columbia Canc Agcy, Canc Control Res Program, Vancouver, BC V5Z 4E6, Canada. RP Friesen, MC (reprint author), NCI, Occupat & Environm Epidemiol Branch, 6120 Execut Blvd, Bethesda, MD 20892 USA. EM friesenmc@mail.nih.gov RI Spinelli, John/B-6210-2013; Friesen, Melissa/A-5362-2009 FU Alcan, Inc.; WorkSafe British Columbia; Alcan-Canadian Auto Workers Advisory Committee; Richard Lapointe FX This research was supported by grants from Alcan, Inc. and WorkSafe British Columbia (formerly the Workers' Compensation Board of British Columbia).; The authors thank the Alcan-Canadian Auto Workers Advisory Committee and Richard Lapointe for their support. They greatly appreciate the assistance provided by staff at the Kitimat operation in the collection of exposure data (Barry Boudreault and Jim Thorne) and work history data (Siok Yeok). The authors also thank WorkSafe British Columbia for providing the personal air samples collected by inspectors. Additionally, they thank the research staff who assisted with this study: Donna Kan, Raymond Fang, Barbara Jamieson, Dianne Oleniuk, Jade Vo, Heather Neidig, Nela Walter, Elena Papadakis, Zenaida Abanto, and Sharon Tamaro.; This research was funded in part by Alcan, Inc. The study design, analyses, and manuscript preparation were conducted independently. This study was carried out with logistical support from an advisory committee consisting of company and union representatives. NR 49 TC 15 Z9 15 U1 1 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD OCT 1 PY 2010 VL 172 IS 7 BP 790 EP 799 DI 10.1093/aje/kwq208 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 654KJ UT WOS:000282166900008 PM 20702507 ER PT J AU Freedman, LS Tasevska, N Kipnis, V Schatzkin, A Mares, J Tinker, L Potischman, N AF Freedman, Laurence S. Tasevska, Natasa Kipnis, Victor Schatzkin, Arthur Mares, Julie Tinker, Lesley Potischman, Nancy TI Gains in Statistical Power From Using a Dietary Biomarker in Combination With Self-reported Intake to Strengthen the Analysis of a Diet-Disease Association: An Example From CAREDS SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE carotenoids; cataract; lutein; ranks; sample size ID HEALTH; CAROTENOIDS; CATARACT; CANCER; EYE AB A major problem in detecting diet-disease associations in nutritional cohort studies is measurement error in self-reported intakes, which causes loss of statistical power. The authors propose using biomarkers correlated with dietary intake to strengthen analyses of diet-disease hypotheses and to increase statistical power. They consider combining self-reported intakes and biomarker levels using principal components or a sum of ranks and relating the combined measure to disease in conventional regression analyses. They illustrate their method in a study of the inverse association of dietary lutein plus zeaxanthin with nuclear cataracts, using serum lutein plus zeaxanthin as the biomarker, with data from the Carotenoids in Age-Related Eye Disease Study (United States, 2001-2004). This example demonstrates that the combined measure provides higher statistical significance than the dietary measure or the serum measure alone, and it potentially provides sample savings of 8%-53% over analysis with dietary intake alone and of 6%-48% over analysis with serum level alone, depending on the definition of the outcome variable and the choice of confounders entered into the regression model. The authors conclude that combining appropriate biomarkers with dietary data in a cohort can strengthen the investigation of diet-disease associations by increasing the statistical power to detect them. C1 [Freedman, Laurence S.] Gertner Inst Epidemiol, Biostat Unit, IL-52161 Tel Hashomer, Israel. [Tasevska, Natasa; Schatzkin, Arthur] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Kipnis, Victor] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. [Mares, Julie] Univ Wisconsin, Sch Med & Publ Hlth, Dept Ophthalmol & Visual Sci, Madison, WI USA. [Tinker, Lesley] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. [Potischman, Nancy] NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Freedman, LS (reprint author), Gertner Inst Epidemiol, Biostat Unit, IL-52161 Tel Hashomer, Israel. EM lsf@actcom.co.il FU National Institutes of Health, Bethesda, Maryland [HHSN261200633000]; National Institutes of Health; National Eye Institute [EY013018, EY016886]; National Heart, Lung, and Blood Institute; Research to Prevent Blindness FX This work was supported by the National Institutes of Health, Bethesda, Maryland (under contract HHSN261200633000 to L. S. F.) and by National Institutes of Health and The National Eye Institute grants EY013018 and EY016886; the National Heart, Lung, and Blood Institute (for support of the WHI); and Research to Prevent Blindness. NR 12 TC 16 Z9 17 U1 0 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD OCT 1 PY 2010 VL 172 IS 7 BP 836 EP 842 DI 10.1093/aje/kwq194 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 654KJ UT WOS:000282166900013 PM 20716705 ER PT J AU Pronk, A Ji, BT Shu, XO Gao, YT Zheng, W Chow, WH AF Pronk, Anjoeka Ji, Bu-Tian Shu, Xiao-Ou Gao, Yu-Tang Zheng, Wei Chow, Wong-Ho TI Untitled REPLY SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Letter C1 [Pronk, Anjoeka; Ji, Bu-Tian; Chow, Wong-Ho] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Shu, Xiao-Ou; Zheng, Wei] Vanderbilt Univ, Vanderbilt Ingram Canc Ctr, Div Epidemiol, Dept Med,Vanderbilt Epidemiol Ctr,Sch Med, Nashville, TN 37232 USA. [Gao, Yu-Tang] Shanghai Canc Inst, Dept Epidemiol, Shanghai 200032, Peoples R China. RP Pronk, A (reprint author), NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. EM choww@mail.nih.gov NR 3 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD OCT 1 PY 2010 VL 172 IS 7 BP 867 EP 868 DI 10.1093/aje/kwq276 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 654KJ UT WOS:000282166900022 ER PT J AU Noureddin, M Ghany, MG AF Noureddin, Mazen Ghany, Marc G. TI Treatment of Patients With HCV-Related Cirrhosis With Peginterferon and Ribavirin: Swinging the Pendulum Toward Treatment SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Editorial Material ID CHRONIC HEPATITIS-C; RANDOMIZED CONTROLLED-TRIAL; VIRUS-RELATED CIRRHOSIS; SUSTAINED VIROLOGICAL RESPONSE; PLUS RIBAVIRIN; PEGYLATED INTERFERON; COMBINATION THERAPY; ADVANCED FIBROSIS; ALPHA-2A; EFFICACY AB Patients with hepatitis C virus-related cirrhosis are at increased risk for hepatic decompensation and hepatocellular carcinoma (HCC). They also responded less well to standard therapy compared with those without cirrhosis. Several recent studies have demonstrated that patients with cirrhosis can be safely treated and those who achieve a sustained virological response have better clinical outcomes compared with nonresponders. These results support treatment for patients with compensated cirrhosis. In addition, cirrhotic patients should be monitored after a sustained virological response is obtained, because some patients remain at risk for complications of liver disease, particularly HCC. Newer, more effective therapy is needed for patients with cirrhosis. C1 [Noureddin, Mazen; Ghany, Marc G.] NIDDKD, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. RP Ghany, MG (reprint author), NIDDKD, Liver Dis Branch, NIH, Bldg 10,Room 9B-16,10 Ctr Dr,MSC 1800, Bethesda, MD 20892 USA. EM marcg@intra.niddk.nih.gov NR 20 TC 3 Z9 3 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2010 VL 105 IS 10 BP 2174 EP 2176 DI 10.1038/ajg.2010.288 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 659US UT WOS:000282593000010 PM 20927065 ER PT J AU Laiyemo, A Tapscott, D Fullum, T Lanza, E Schatzkin, A Smoot, D Cross, A AF Laiyemo, Adeyinka Tapscott, Denia Fullum, Terrence Lanza, Elaine Schatzkin, Arthur Smoot, Duane Cross, Amanda TI The Association of Obesity with Short- and Long-Term Risk of Adenoma Recurrence: Analysis of the Polyp Prevention Trial and Continued Follow-Up Study SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 75th Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 15-20, 2010 CL San Antonio, TX SP Amer Coll Gastroenterol C1 [Laiyemo, Adeyinka; Tapscott, Denia; Fullum, Terrence; Smoot, Duane] Howard Univ, Washington, DC 20059 USA. [Lanza, Elaine; Schatzkin, Arthur; Cross, Amanda] NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2010 VL 105 SU 1 MA 1496 BP S555 EP S556 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 663VG UT WOS:000282917701683 ER PT J AU Romero, Y Francis, D Grothe, R Jung, KW Namasivayam, V Crowell, M Enders, F Diehl, N Dabade, T Murray, J Alexander, J Adamson, S DeJesus, R Majka, A Prasad, G O'Neil, A Katzka, D Van Norstrand, M Abdalla, A McElhiney, J Geno, D Pasha, S Fredericksen, M Arora, A AF Romero, Yvonne Francis, Dawn Grothe, Rayna Jung, Kee Wook Namasivayam, Vikneswaran Crowell, Michael Enders, Felicity Diehl, Nancy Dabade, Tushar Murray, Joseph Alexander, Jeffrey Adamson, Steven DeJesus, Ramona Majka, Andrew Prasad, Ganapathy O'Neil, Angela Katzka, David Van Norstrand, Michael Abdalla, Adil McElhiney, Judith Geno, Debra Pasha, Shabana Fredericksen, Mary Arora, Amindra TI Randomized Open-label Trial to Assess the Impact of Dosage Timing of Omeprazole/Sodium Bicarbonate (Zegerid 40 mg) on Healing of Severe Reflux Esophagitis: A Progress Report SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 75th Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 15-20, 2010 CL San Antonio, TX SP Amer Coll Gastroenterol C1 [Romero, Yvonne; Francis, Dawn; Grothe, Rayna; Jung, Kee Wook; Namasivayam, Vikneswaran; Enders, Felicity; Dabade, Tushar; Murray, Joseph; Alexander, Jeffrey; Adamson, Steven; DeJesus, Ramona; Majka, Andrew; Prasad, Ganapathy; O'Neil, Angela; Katzka, David; Geno, Debra; Fredericksen, Mary; Arora, Amindra] Mayo Clin, Rochester, MN USA. [Crowell, Michael; Pasha, Shabana] Mayo Clin, Scottsdale, AZ USA. [Diehl, Nancy] Mayo Clin, Jacksonville, FL 32224 USA. [Van Norstrand, Michael] FSH Mayo Clin, La Crosse, WI USA. [Abdalla, Adil] NIDDK, NIH, Rockville, MD USA. [McElhiney, Judith] Gunderson Lutheran Hlth Syst, La Crosse, WI USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2010 VL 105 SU 1 MA 59 BP S22 EP S22 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 663VG UT WOS:000282917700060 ER PT J AU Senadhi, V Arora, D Arora, M Dutta, S AF Senadhi, Viplove Arora, Deepika Arora, Manish Dutta, Sudhir TI A Mysterious Cause of Upper Gastrointestinal Bleeding Presenting Surreptitiously SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 75th Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 15-20, 2010 CL San Antonio, TX SP Amer Coll Gastroenterol C1 [Senadhi, Viplove] Johns Hopkins Univ, Sinai Hosp, Baltimore, MD USA. [Arora, Deepika] N Gen Hosp, Mt Sinai Sch Med, New York, NY USA. [Arora, Manish] Univ Maryland, Sch Med, Div Gastroenterol, Baltimore, MD 21201 USA. [Arora, Manish] NIH, Baltimore, MD USA. [Dutta, Sudhir] Sinai Hosp, Div Gastroenterol, Baltimore, MD 21215 USA. RI Senadhi, Viplove/F-1817-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2010 VL 105 SU 1 MA 725 BP S262 EP S262 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 663VG UT WOS:000282917700719 ER PT J AU Senadhi, V Arora, D Arora, M Mackrell, P AF Senadhi, Viplove Arora, Deepika Arora, Manish Mackrell, Peter TI Recurrent Gastrointestinal Bleeding from an Occult Source SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 75th Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 15-20, 2010 CL San Antonio, TX SP Amer Coll Gastroenterol C1 [Senadhi, Viplove] Johns Hopkins Univ, Sinai Hosp, Baltimore, MD USA. [Arora, Deepika] Mt Sinai Sch Med, N Gen Hosp, New York, NY USA. [Arora, Manish] Univ Maryland, Sch Med, Div Gastroenterol, Washington, DC USA. [Arora, Manish] NIH, Washington, DC USA. [Mackrell, Peter] Sinai Hosp, Dept Vasc Surg, Baltimore, MD 21215 USA. RI Senadhi, Viplove/F-1817-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2010 VL 105 SU 1 MA 1003 BP S363 EP S363 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 663VG UT WOS:000282917701191 ER PT J AU Donsante, A Johnson, P Jansen, LA Kaler, SG AF Donsante, Anthony Johnson, Paul Jansen, Laura A. Kaler, Stephen G. TI Somatic Mosaicism in Menkes Disease Suggests Choroid Plexus-Mediated Copper Transport to the Developing Brain SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE somatic mosaicism; Menkes disease; ATP7A; copper metabolism; choroid plexus ID CEREBROSPINAL-FLUID; CANDIDATE GENE; BLOOD; DIAGNOSIS; BARRIER; DEFICIENCY; EXPRESSION; ATPASES; ENCODES; PATTERN AB The primary mechanism of copper transport to the brain is unknown, although this process is drastically impaired in Menkes disease, an X-linked neurodevelopmental disorder caused by mutations in an evolutionarily conserved copper transporter, ATP7A. Potential central nervous system entry routes for copper include brain capillary endothelial cells that originate from mesodermal angioblasts and form the blood-brain barrier, and the choroid plexuses, which derive from embryonic ectoderm, and form the blood-cerebrospinal fluid barrier. We exploited a rare (and first reported) example of somatic mosaicism for an ATP7A mutation to shed light on questions about copper transport into the developing brain. In a 20-month-old Menkes disease patient evaluated before copper treatment, blood copper, and catecholamine concentrations were normal, whereas levels in cerebrospinal fluid were abnormal and consistent with his neurologically severe phenotype. We documented disparate levels of mosaicism for an ATP7A missense mutation, P1001L, in tissues derived from different embryonic origins; allele quantitation showed P1001L in approximately 27% of DNA samples from blood cells (mesoderm-derived) and 88% from cultured fibroblasts (ectoderm-derived). These findings imply that the P1001L mutation in the patient preceded formation of the three primary embryonic lineages at gastrulation, with the ectoderm layer ultimately harboring a higher percentage of mutation-bearing cells than mesoderm or endoderm. Since choroid plexus epithelia are derived from neuroectoderm, and brain capillary endothelial cells from mesodermal angioblasts, the clinical and biochemical findings in this infant support a critical role for the blood-CSF barrier (choroid plexus epithelia) in copper entry to the developing brain. Published (C) 2010 Wiley-Liss, Inc.(dagger) C1 [Donsante, Anthony; Johnson, Paul; Kaler, Stephen G.] Eunice Kennedy Shriver NICHD, Unit Human Copper Metab, Program Mol Med, NIH, Bethesda, MD 20892 USA. [Jansen, Laura A.] Univ Washington, Div Pediat Neurol, Seattle Childrens Hosp Res Inst, Seattle, WA 98195 USA. RP Kaler, SG (reprint author), Eunice Kennedy Shriver NICHD, Unit Human Copper Metab, Program Mol Med, NIH, Bldg 10,Room 10N313,10 Ctr Dr MSC 1853, Bethesda, MD 20892 USA. EM kalers@mail.nih.gov FU NIH FX We gratefully acknowledge the patient and his family for participation in this study. This work was supported by the NIH intramural research program. NR 49 TC 22 Z9 23 U1 1 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD OCT PY 2010 VL 152A IS 10 BP 2529 EP 2534 DI 10.1002/ajmg.a.33632 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 666GX UT WOS:000283103700013 PM 20799318 ER PT J AU Chetty-John, S Piwnica-Worms, K Bryant, J Bernardini, I Fischer, RE Heller, T Gahl, WA Gunay-Aygun, M AF Chetty-John, Shilpa Piwnica-Worms, Katie Bryant, Joy Bernardini, Ise Fischer, Roxanne E. Heller, Theo Gahl, William A. Gunay-Aygun, Meral TI Fibrocystic Disease of Liver and Pancreas; Under-Recognized Features of the X-Linked Ciliopathy Oral-Facial-Digital Syndrome Type 1 (OFD I) SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE oral facial digital type I; ciliopathy; pancreatic cysts; polycytsic kidney disease; congenital hepatic fibrosis; caroli disease ID POLYCYSTIC KIDNEY-DISEASE; STAGE RENAL-DISEASE; OROFACIODIGITAL SYNDROME; PATIENT; MALFORMATIONS; ABNORMALITIES; PATHOGENESIS; MECHANISMS; PROGNOSIS; FAILURE AB OFD I is an X-linked dominant male-lethal ciliopathy characterized by prominent external features including oral clefts, hamartomas or cysts of the tongue, and digital anomalies. Although these external features are easy to recognize and often lead to diagnosis in early childhood, visceral findings in OFD I, especially the fibrocystic liver and pancreas disease, are under-recognized. In addition, while the occurrence of polycystic kidney disease (PKD) in OFD I is well known, few patients are evaluated and monitored for this complication. We report on two adult females diagnosed with OFD I in infancy, but not evaluated for visceral involvement. In adulthood, they were incidentally found to have severe hypertension and chronic renal insufficiency due to undiagnosed PKD. A pancreatic cystic lesion, also discovered incidentally, was thought to be malignant and led to consideration of major surgery. We present NIH evaluations, including documentation of OFD I mutations, extreme beading of the intrahepatic bile ducts, pancreatic cysts, and tabulate features of reported OFD I cases having hepatic, pancreatic, and renal cystic disease. Liver and pancreas are not routinely evaluated in OFD I patients. Increased awareness and lifelong monitoring of visceral complications, particularly involving the liver, pancreas, and kidney, are essential for timely and accurate treatment. Published 2010 Wiley-Liss, Inc.(dagger) C1 [Chetty-John, Shilpa; Piwnica-Worms, Katie; Bryant, Joy; Bernardini, Ise; Fischer, Roxanne E.; Gahl, William A.; Gunay-Aygun, Meral] NHGRI, NIH, Med Genet Branch, Bethesda, MD 20892 USA. [Heller, Theo] NIDDK, NIH, Bethesda, MD USA. [Gunay-Aygun, Meral] NIH, Off Rare Dis Res, Off Director, Bethesda, MD 20892 USA. RP Gunay-Aygun, M (reprint author), NHGRI, NIH, Med Genet Branch, 10 Ctr Dr 10C103A, Bethesda, MD 20892 USA. EM mgaygun@mail.nih.gov FU National Human Genome Research Institute; NIH Clinical Center FX Grant sponsor: National Human Genome Research Institute; Grant sponsor: NIH Clinical Center. NR 35 TC 11 Z9 11 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD OCT PY 2010 VL 152A IS 10 BP 2640 EP 2645 DI 10.1002/ajmg.a.33666 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 666GX UT WOS:000283103700032 PM 20818665 ER PT J AU Staretz-Chacham, O Choi, JH Wakabayashi, K Lopez, G Sidransky, E AF Staretz-Chacham, Orna Choi, Jae Hyuk Wakabayashi, Kazuyo Lopez, Grisel Sidransky, Ellen TI Psychiatric and Behavioral Manifestations of Lysosomal Storage Disorders SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Review DE lysosomal storage disorders; behavioral abnormalities; psychiatric disorders; genetic disorders; enzyme deficiency ID TAY-SACHS-DISEASE; NEURONAL CEROID-LIPOFUSCINOSIS; MUCOPOLYSACCHARIDOSIS TYPE-III; ADULT GM2 GANGLIOSIDOSIS; NIEMANN-PICK-DISEASE; SANFILIPPO TYPE-B; METACHROMATIC LEUKODYSTROPHY; GAUCHER-DISEASE; FABRY-DISEASE; BETA-MANNOSIDOSIS AB The different lysosomal storage disorders (LSDs) manifest with a wide spectrum of clinical presentations. Most of these disorders are typically diagnosed early in life, due to the severity of the associated phenotypes. However, it is important to appreciate that some of the LSDs present later in adolescence or adulthood. The diverse findings triggering the initial diagnosis, as well as the range of manifestations arising later during the disease course, contribute to the complexity of these issues. Clinical presentations occurring at a more advanced age, especially psychiatric and behavioral manifestations, can be overlooked or misdiagnosed. This review describes different psychiatric and behavioral manifestations encountered in individuals with LSDs, including psychosis, schizophrenia, mood disorders, aggressiveness, early-onset dementia, and conduct disorder. Twelve different disorders are presented, including descriptions of their associated biochemical abnormalities, clinical presentations, pathology, epidemiology, and genetics. In addition, discussions of neurocognitive, behavioral, and psychiatric findings are outlined for each disorder. A greater awareness of these features may help to reduce missed diagnoses, to avoid unnecessary, invasive and expensive testing, and to facilitate an earlier detection of these rare disorders. Earlier diagnosis can enable the implementation of appropriate interventions and improve genetic counseling. (c) 2010 Wiley-Liss, Inc. C1 [Choi, Jae Hyuk; Wakabayashi, Kazuyo; Lopez, Grisel; Sidransky, Ellen] NHGRI, Sect Mol Neurogenet, Med Genet Branch, NIH, Bethesda, MD 20892 USA. [Staretz-Chacham, Orna] NHGRI, Off Clin Director, NIH, Bethesda, MD 20892 USA. RP Sidransky, E (reprint author), NHGRI, Sect Mol Neurogenet, Med Genet Branch, NIH, Bldg 35,Room 1A213,35 Convent Dr,MSC 3708, Bethesda, MD 20892 USA. EM sidranse@mail.nih.gov NR 82 TC 7 Z9 7 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD OCT PY 2010 VL 153B IS 7 BP 1253 EP 1265 DI 10.1002/ajmg.b.31097 PG 13 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 658KS UT WOS:000282489500001 PM 20872765 ER PT J AU Knight, J Rochberg, NS Saccone, SF Nurnberger, JI Rice, JP AF Knight, Jo Rochberg, Nanette S. Saccone, Scott F. Nurnberger, John I., Jr. Rice, John P. CA NIMH Genetics Initiative Bipolar TI An Investigation of Candidate Regions for Association With Bipolar Disorder SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE bipolar disorder; genetics; association ID GENOME-WIDE ASSOCIATION; LINKAGE ANALYSES; CHROMOSOMES 6Q; RECENT ISSUES; I DISORDER; GENETICS; LOCI; SCHIZOPHRENIA; SUSCEPTIBILITY; DEPRESSION AB We performed a case-control study of 1,000 cases and 1,028 controls on 1,509 markers, 1,139 of which were located in a 8 Mb region on chromosome 6 (105-113 Mb). This region has shown evidence of involvement in bipolar disorder (BP) in a number of other studies. We find association between BP and two SNPs in the gene LACE1. SNP rs9486880 and rs11153113 (both have P-values of 2 x 10(-5)). Both P-values are in the top 5% of the distribution derived from null simulations (P 0.02 and 0.01, respectively). LACE is a good candidate for BP; it is an ATPase. We genotyped 173 other markers in 17 other positional and/or functional loci but found no further evidence of association with BP. (c) 2010 Wiley-Liss, Inc. C1 [Knight, Jo] Guys Hosp, Dept Med & Mol Genet, Kings Coll London, Sch Med, London SE1 9RT, England. [Knight, Jo] Kings Coll London, NIHR, Biomed Res Ctr, Guys & St Thomas NHS Fdn Trust, London WC2R 2LS, England. [Rochberg, Nanette S.; Saccone, Scott F.; Rice, John P.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. NIMH, Clin Sci Lab, Intramural Res Program, US Dept HHS,NIH, Bethesda, MD 20892 USA. Univ Penn, Philadelphia, PA 19104 USA. Rush Univ, Med Ctr, Dept Psychiat, Chicago, IL 60612 USA. NIMH, Unit Genet Basis Mood & Anxiety Disorders, Mood & Anxiety Disorders Program, US Dept HHS,NIH, Bethesda, MD 20892 USA. Univ Iowa, Dept Psychiat, Carver Coll Med, Iowa City, IA 52242 USA. [Nurnberger, John I., Jr.] Indiana Univ, Sch Med, Dept Psychiat, Indianapolis, IN 46202 USA. [NIMH Genetics Initiative Bipolar] Howard Univ, Dept Psychiat, Washington, DC 20059 USA. RP Knight, J (reprint author), Guys Hosp, Dept Med & Mol Genet, Kings Coll London, Sch Med, 8th Floor Tower Wing, London SE1 9RT, England. EM jo.knight@kcl.ac.uk RI Knight, Jo/F-4946-2011; OI Nurnberger, John/0000-0002-7674-1767; McMahon, Francis/0000-0002-9469-305X; Knight, Joanne/0000-0002-7148-1660 FU National Institute for Health Research (NIHR); NIH [5R01MH059534-08, U24 MH068457]; National Institute of Mental Health FX Grant sponsor: National Institute for Health Research (NIHR); Grant sponsor: NIH; Grant numbers: 5R01MH059534-08, U24 MH068457; Grant sponsor: National Institute of Mental Health. NR 37 TC 2 Z9 2 U1 2 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD OCT PY 2010 VL 153B IS 7 BP 1292 EP 1297 DI 10.1002/ajmg.b.31100 PG 6 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 658KS UT WOS:000282489500005 PM 20872768 ER PT J AU Chetty-John, S Zhang, J Chen, Z Albert, P Sun, LP Klebanoff, M Grewal, U AF Chetty-John, Shilpa Zhang, Jun Chen, Zhen Albert, Paul Sun, Liping Klebanoff, Mark Grewal, Una TI Long-term physical and neurologic development in newborn infants with isolated single umbilical artery SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 30th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 01-06, 2010 CL Chicago, IL SP Soc Maternal Fetal Med, Univ Texas Med Branch, Dept Obstetrics & Gynecology DE growth; longitudinal; neurodevelopment; single umbilical artery ID GROWTH ASSESSMENT AB OBJECTIVE: This study compared birth parameters and the longitudinal course in physical and neurologic development between children with 2 and 3 vessel umbilical cords. STUDY DESIGN: Our study of the Collaborative Perinatal Project included singletons of at least 24 weeks' gestation with single umbilical artery at birth and no identifiable congenital anomalies. Demographics that were collected included maternal age, race, smoking status, and socioeconomic index. Delivery data included gestational age, birth-weight, Apgar scores, placental weight, and umbilical cord insertion and length. Growth and neurodevelopmental parameters were collected at various intervals from birth to 7 years. RESULTS: There were 263 infants with isolated single umbilical artery and 41,415 infants with 3 vessel cords. A random effect model that controlled for potential confounders did not show clinically significant differences in the physical and neurodevelopment measures between these groups. CONCLUSION: Our study shows no evidence of differential longitudinal physical growth or neurologic outcomes between infants with 2 or 3 vessel cords. C1 [Chetty-John, Shilpa] NHGRI, NIH, Bethesda, MD 20892 USA. [Zhang, Jun; Chen, Zhen; Albert, Paul; Sun, Liping; Klebanoff, Mark; Grewal, Una] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD 20892 USA. RP Chetty-John, S (reprint author), Stanford Univ, Med Ctr, Dept OB Gyn, 300 Pasteur Dr,Room HH333, Stanford, CA 94305 USA. EM schetty@stanford.edu FU Intramural NIH HHS [Z99 HD999999] NR 18 TC 2 Z9 4 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD OCT PY 2010 VL 203 IS 4 AR 368.e1 DI 10.1016/j.ajog.2010.06.031 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 655WT UT WOS:000282287000040 PM 20723870 ER PT J AU Romero, R Friel, LA Edwards, DRV Kusanovic, JP Hassan, SS Mazaki-Tovi, S Vaisbuch, E Kim, CJ Erez, O Chaiworapongsa, T Pearce, BD Bartlett, J Salisbury, BA Anant, MK Vovis, GF Lee, MS Gomez, R Behnke, E Oyarzun, E Tromp, G Williams, SM Menon, R AF Romero, Roberto Friel, Lara A. Edwards, Digna R. Velez Kusanovic, Juan Pedro Hassan, Sonia S. Mazaki-Tovi, Shali Vaisbuch, Edi Kim, Chong Jai Erez, Offer Chaiworapongsa, Tinnakorn Pearce, Brad D. Bartlett, Jacquelaine Salisbury, Benjamin A. Anant, Madan Kumar Vovis, Gerald F. Lee, Min Seob Gomez, Ricardo Behnke, Ernesto Oyarzun, Enrique Tromp, Gerard Williams, Scott M. Menon, Ramkumar TI A genetic association study of maternal and fetal candidate genes that predispose to preterm prelabor rupture of membranes (PROM) SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE chorioamnionitis; DNA variants; extracellular matrix; genetic association study; genomics; genotype; haplotype; high dimensional biology; matrix metalloproteinase; parturition; prematurity; preterm prelabor rupture of membranes; single-nucleotide polymorphism ID TUMOR-NECROSIS-FACTOR; INTERLEUKIN-1 RECEPTOR ANTAGONIST; MIDTRIMESTER AMNIOTIC-FLUID; FACTOR-ALPHA GENE; PROINFLAMMATORY CYTOKINE POLYMORPHISMS; MULTIFACTOR-DIMENSIONALITY REDUCTION; SINGLE NUCLEOTIDE POLYMORPHISMS; HARDY-WEINBERG EQUILIBRIUM; EHLERS-DANLOS-SYNDROME; FALSE DISCOVERY RATE AB OBJECTIVE: We sought to determine whether maternal/fetal single-nucleotide polymorphisms (SNPs) in candidate genes are associated with preterm prelabor rupture of membranes (pPROM). STUDY DESIGN: A case-control study was conducted in patients with pPROM (225 mothers and 155 fetuses) and 599 mothers and 628 fetuses with a normal pregnancy; 190 candidate genes and 775 SNPs were studied. Single locus/haplotype association analyses were performed; false discovery rate was used to correct for multiple testing (q(star) = 0.15). RESULTS: First, a SNP in tissue inhibitor of metalloproteinase 2 in mothers was significantly associated with pPROM (odds ratio, 2.12; 95% confidence interval, 1.47-3.07; P = .000068), and this association remained significant after correction for multiple comparisons. Second, haplotypes for Alpha 3 type IV collagen isoform precursor in the mother were associated with pPROM ( global P = .003). Third, multilocus analysis identified a 3-locus model, which included maternal SNPs in collagen type I alpha 2, defensin alpha 5 gene, and endothelin 1. CONCLUSION: DNA variants in a maternal gene involved in extracellular matrix metabolism doubled the risk of pPROM. C1 [Romero, Roberto; Friel, Lara A.; Kusanovic, Juan Pedro; Hassan, Sonia S.; Mazaki-Tovi, Shali; Vaisbuch, Edi; Kim, Chong Jai; Erez, Offer; Chaiworapongsa, Tinnakorn] Wayne State Univ, Hutzel Womens Hosp, Perinatol Res Branch,NIH,Dept Hlth & Human Serv, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Detroit, MI 48201 USA. [Romero, Roberto; Friel, Lara A.; Kusanovic, Juan Pedro; Hassan, Sonia S.; Mazaki-Tovi, Shali; Vaisbuch, Edi; Kim, Chong Jai; Erez, Offer; Chaiworapongsa, Tinnakorn] Wayne State Univ, Hutzel Womens Hosp, Perinatol Res Branch,NIH,Dept Hlth & Human Serv, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. [Romero, Roberto; Tromp, Gerard] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI 48201 USA. [Romero, Roberto; Friel, Lara A.; Kusanovic, Juan Pedro; Hassan, Sonia S.; Mazaki-Tovi, Shali; Vaisbuch, Edi; Erez, Offer; Chaiworapongsa, Tinnakorn] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI 48201 USA. [Kim, Chong Jai] Wayne State Univ, Dept Pathol, Detroit, MI 48201 USA. [Edwards, Digna R. Velez] Vanderbilt Univ, Vanderbilt Epidemiol Ctr, Inst Med & Publ Hlth, Nashville, TN USA. [Edwards, Digna R. Velez] Vanderbilt Univ, Dept Obstet & Gynecol, Nashville, TN USA. [Bartlett, Jacquelaine; Williams, Scott M.] Vanderbilt Univ, Ctr Human Genet Res, Nashville, TN USA. [Williams, Scott M.] Vanderbilt Univ, Dept Mol Physiol & Biophys, Nashville, TN USA. [Pearce, Brad D.; Menon, Ramkumar] Emory Univ, Dept Epidemiol, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. [Salisbury, Benjamin A.; Anant, Madan Kumar] PGxHlth LLC, New Haven, CT USA. [Vovis, Gerald F.] Helix Therapeut LLC, New Haven, CT USA. [Lee, Min Seob] Genaissance Pharmaceut Inc, New Haven, CT USA. [Gomez, Ricardo; Behnke, Ernesto] Pontificia Univ Catolica Chile, Dept Obstet & Gynecol, Ctr Perinatal Diag & Res, Sotero del Rio Hosp, Santiago, Chile. RP Romero, R (reprint author), Wayne State Univ, Hutzel Womens Hosp, Perinatol Res Branch,NIH,Dept Hlth & Human Serv, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, 3990 John R,Box 4, Detroit, MI 48201 USA. EM prbchiefstaff@med.wayne.edu RI Williams, Scott/B-9491-2012; Velez Edwards, Digna/C-1090-2012; Tromp, Gerard/B-2677-2017; OI Tromp, Gerard/0000-0002-7761-0806; Vaisbuch, Edi/0000-0002-8400-9031; Salisbury, Benjamin/0000-0003-0796-6492 FU Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services FX This research was supported, in part, by the Perinatology Research Branch, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services. NR 195 TC 2 Z9 5 U1 1 U2 12 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD OCT PY 2010 VL 203 IS 4 AR 361.e1 DI 10.1016/j.ajog.2010.05.026 PG 30 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 655WT UT WOS:000282287000034 PM 20673868 ER PT J AU Zhang, J Troendle, J Reddy, UM Laughon, SK Branch, DW Burkman, R Landy, HJ Hibbard, JU Haberman, S Ramirez, MM Bailit, JL Hoffman, MK Gregory, KD Gonzalez-Quintero, VH Kominiarek, M Learman, LA Hatjis, CG van Veldhuisen, P AF Zhang, Jun Troendle, James Reddy, Uma M. Laughon, S. Katherine Branch, D. Ware Burkman, Ronald Landy, Helain J. Hibbard, Judith U. Haberman, Shoshana Ramirez, Mildred M. Bailit, Jennifer L. Hoffman, Matthew K. Gregory, Kimberly D. Gonzalez-Quintero, Victor H. Kominiarek, Michelle Learman, Lee A. Hatjis, Christos G. van Veldhuisen, Paul CA Consortium Safe Labor TI Contemporary cesarean delivery practice in the United States SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE cesarean delivery; induction; labor; vaginal birth after previous cesarean ID VAGINAL BIRTH; PREGNANCY OUTCOMES; PERINATAL HEALTH; GLOBAL SURVEY; LABOR; SECTION; RATES AB OBJECTIVE: To describe contemporary cesarean delivery practice in the United States. STUDY DESIGN: Consortium on Safe Labor collected detailed labor and delivery information from 228,668 electronic medical records from 19 hospitals across the United States, 2002-2008. RESULTS: The overall cesarean delivery rate was 30.5%. The 31.2% of nulliparous women were delivered by cesarean section. Prelabor repeat cesarean delivery due to a previous uterine scar contributed 30.9% of all cesarean sections. The 28.8% of women with a uterine scar had a trial of labor and the success rate was 57.1%. The 43.8% women attempting vaginal delivery had induction. Half of cesarean for dystocia in induced labor were performed before 6 cm of cervical dilation. CONCLUSION: To decrease cesarean delivery rate in the United States, reducing primary cesarean delivery is the key. Increasing vaginal birth after previous cesarean rate is urgently needed. Cesarean section for dystocia should be avoided before the active phase is established, particularly in nulliparous women and in induced labor. C1 [Zhang, Jun; Troendle, James; Reddy, Uma M.; Laughon, S. Katherine] NICHHD, NIH, Bethesda, MD 20892 USA. [Branch, D. Ware] Intermountain HealthCare & Univ Utah, Salt Lake City, UT USA. [Burkman, Ronald] Baystate Med Ctr, Springfield, MA USA. [Landy, Helain J.] Georgetown Univ Hosp, MedStar Hlth, Washington, DC 20007 USA. [Hibbard, Judith U.] Univ Illinois, Chicago, IL USA. [Haberman, Shoshana] Maimonides Hosp, Brooklyn, NY 11219 USA. [Ramirez, Mildred M.] Univ Texas Hlth Sci Ctr Houston, Houston, TX USA. [Bailit, Jennifer L.] MetroHlth Med Ctr, Cleveland, OH USA. [Hoffman, Matthew K.] Christiana Care Hlth Syst, Wilmington, DE USA. [Gregory, Kimberly D.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Gonzalez-Quintero, Victor H.] Univ Miami, Miami, FL USA. [Kominiarek, Michelle; Learman, Lee A.] Indiana Univ, Clarian Hlth, Indianapolis, IN 46204 USA. [Hatjis, Christos G.] Akron City Hosp, Summa Hlth Syst, Akron, OH USA. [van Veldhuisen, Paul] EMMES Corp, Rockville, MD USA. RP Zhang, J (reprint author), NICHHD, NIH, Bethesda, MD 20892 USA. OI Grantz, Katherine/0000-0003-0276-8534 FU Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health [HHSN267200603425C] FX The Consortium on Safe Labor was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, through Contract no. HHSN267200603425C. NR 26 TC 57 Z9 59 U1 1 U2 13 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD OCT PY 2010 VL 203 IS 4 AR 326.e1 DI 10.1016/j.ajog.2010.06.058 PG 10 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 655WT UT WOS:000282287000019 PM 20708166 ER PT J AU Singh, S Vinson, C Gurley, CM Nolen, GT Beggs, ML Nagarajan, R Wagner, EF Parham, DM Peterson, CA AF Singh, Shalini Vinson, Charles Gurley, Cathy M. Nolen, Greg T. Beggs, Marjorie L. Nagarajan, Radhakrishnan Wagner, Erwin F. Parham, David M. Peterson, Charlotte A. TI Impaired Wnt Signaling in Embryonal Rhabdomyosarcoma Cells from p53/c-fos Double Mutant Mice SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID CHILDRENS ONCOLOGY GROUP; BETA-CATENIN; GROWTH-FACTOR; C-FOS; SKELETAL-MUSCLE; TUMOR-GROWTH; EXPRESSION; AP-1; GENE; TUMORIGENESIS AB Rhabdomyosarcoma is a primitive neoplasm with a poorly understood etiology that exhibits features of fetal skeletal muscle. It represents the most frequent malignant soft tissue sarcoma affecting the pediatric population and is often treated very aggressively. Embryonal rhabdomyosarcoma (ERMS) and alveolar rhabdomyosarcoma constitute the two major subtypes and exhibit different molecular features. We investigated one potential molecular basis for ERMS by using cells derived from tumors produced in p53(-/-)/c-fos(-/-)mice. This model closely recapitulates the timing, location, molecular markers, and histology seen in human ERMS. A combined chromatin immunoprecipitation/promoter microarray approach was used to identify promoters bound by the c-Jun-containing AP-1 complex In the tumor-derived cells that lacked c-Fos. Identification of the Wnt2 gene and its overexpression in ERMS cells was confirmed in human rhabdomyosarcoma cell lines and prompted further analysis of the Wnt signaling pathway. Contrary to our expectations, the canonical Wnt/beta-catenin signaling pathway was down-regulated in ERMS cells compared with normal myoblasts, and activating this pathway promoted myogenic differentiation. Furthermore, the identification of both survivin and sfrp2 through promoter and expression analyses suggested that increased resistance to apoptosis was associated with the inhibition of the Wnt signaling pathway. These results suggest that altered AP-1 activity that leads to the down-regulation of the Wnt pathway may contribute to the inhibition of myogenic differentiation and resistance to apoptosis in ERMS cases. (Am J Pathol 2010, 177:2055-2066. DOI: 10.2353/ajpath.2010.091195) C1 [Peterson, Charlotte A.] Univ Kentucky, Coll Hlth Sci, Lexington, KY USA. [Parham, David M.] Univ Oklahoma, Hlth Sci Ctr, Dept Pathol, Oklahoma City, OK USA. [Wagner, Erwin F.] Ctr Nacl Invest Oncol, Madrid, Spain. [Vinson, Charles] NCI, NIH, Bethesda, MD 20892 USA. [Singh, Shalini; Gurley, Cathy M.; Nolen, Greg T.; Beggs, Marjorie L.; Nagarajan, Radhakrishnan] Univ Arkansas Med Sci, Dept Geriatr, Little Rock, AR 72205 USA. RP Peterson, CA (reprint author), 900 S Limestone,CTW 105, Lexington, KY 40536 USA. EM cpete4@uky.edu RI Wagner, Erwin/G-9637-2012 OI Wagner, Erwin/0000-0001-7872-0196 FU National Institutes of Health [AG20941]; University of Arkansas for Medical Sciences Microarray Facility FX Supported by grant AG20941 to C.A.P. from the National Institutes of Health and by the University of Arkansas for Medical Sciences Microarray Facility through Act 1, The Arkansas Tobacco Settlement Proceeds Act of 2000. NR 65 TC 15 Z9 19 U1 2 U2 3 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD OCT PY 2010 VL 177 IS 4 BP 2055 EP 2066 DI 10.2353/ajpath.2010.091195 PG 12 WC Pathology SC Pathology GA 658NG UT WOS:000282496100047 PM 20829439 ER PT J AU Gaskins, RB LaGasse, LL Liu, J Shankaran, S Lester, BM Bada, HS Bauer, CR Das, A Higgins, RD Roberts, M AF Gaskins, Ronnesia B. LaGasse, Linda L. Liu, Jing Shankaran, Seetha Lester, Barry M. Bada, Henrietta S. Bauer, Charles R. Das, Abhik Higgins, Rosemary D. Roberts, Mary TI Small for Gestational Age and Higher Birth Weight Predict Childhood Obesity in Preterm Infants SO AMERICAN JOURNAL OF PERINATOLOGY LA English DT Article DE Childhood obesity; premature birth; infant SGA; birth weight; exercise; prenatal drug exposure ID MATERNAL LIFE-STYLE; BODY-MASS INDEX; CORONARY-HEART-DISEASE; CATCH-UP GROWTH; UNITED-STATES; FETAL-GROWTH; CARDIOVASCULAR-DISEASE; PROSPECTIVE COHORT; OVERWEIGHT STATUS; POSTNATAL-GROWTH AB We sought to determine the association between small for gestational age (SGA), birth weight, and childhood obesity within preterm polysubstance exposed children. We sampled 312 preterm children with 11-year body mass index (BMI; age- and sex-specific) data from the Maternal Lifestyle Study (51% girls, 21.5% SGA, 46% prenatal cocaine, and 55% tobacco exposed). Multinomial regression analyzed the association between 11-year obesity (OBE) and overweight (OW) and SGA, birth weight, first-year growth velocity, diet, and physical activity variables. Overall, 24% were OBE (BMI for age >= 95th percentile) and 16.7% were OW (BMI >= 85th and <95th percentiles). In adjusted analyses, SGA was associated with OW (odds ratio [OR] = 3.4, confidence interval [CI] 1.5 to 7.5). Higher birth weight was associated with OBE (OR 1.8, CI 1.3 to 2.4) and OW (OR 1.4, CI 1.1 to 2.0). Growth velocity was associated with OBE (OR = 2.7, CI 1.8 to 4.0) and OW(OR = 1.6, CI 1.1 to 2.4). Low exercise was associated with OBE (OR = 2.1, CI 1.0 to 4.4) and OW (OR = 2.1, CI 1.0 to 4.5). There was no effect of substance exposure on obesity outcomes. Many (41%) of these high-risk preterm 11-year-olds were obese/overweight. Multiple growth-related processes may be involved in obesity risk for preterm children, including fetal programming as indicated by the SGA effect. C1 [Gaskins, Ronnesia B.; LaGasse, Linda L.; Liu, Jing; Lester, Barry M.; Roberts, Mary] Women & Infants Hosp Rhode Isl, Brown Ctr Study Children Risk, Brown Alpert Med Sch, Providence, RI 02905 USA. [Shankaran, Seetha] Wayne State Univ, Dept Pediat, Detroit, MI 48202 USA. [Bada, Henrietta S.] Univ Kentucky, Lexington, KY USA. [Bauer, Charles R.] Univ Miami, Leonard M Miller Sch Med, Miami, FL USA. [Das, Abhik] RTI Int, Rockville, MD USA. [Higgins, Rosemary D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. RP Gaskins, RB (reprint author), Women & Infants Hosp Rhode Isl, Brown Ctr Study Children Risk, Brown Alpert Med Sch, 101 Dudley St, Providence, RI 02905 USA. EM Ronnesia_Gaskins@brown.edu FU National Institutes of Health; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); National Institute on Drug Abuse (NIDA); Administration on Children, Youth, and Families; Center for Substance Abuse and Treatment; NIDA; NICHD; National Institute of Mental Health (NIMH) FX The National Institutes of Health; the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); the National Institute on Drug Abuse (NIDA); the Administration on Children, Youth, and Families; and the Center for Substance Abuse and Treatment provided grant support for recruiting subjects into the Maternal Lifestyle Study in 1993 to 1995. NIDA and NICHD provided funding to conduct follow-up examinations in five phases: at 1, 4, 8, 10, 12, 18, 24, and 36 months' corrected age (phase I and phase II); at 31/2, 4, 41/2, 5, 51/2, 6, and 7 years of age (phase III); and at 8, 9, 10, and 11 years of age (phase IV). NICHD, NIDA, and the National Institute of Mental Health (NIMH) provided continuing funding to conduct follow-up examinations at ages 12, 13, 14, 15, and 16 years (phase V). The funding agencies provided overall oversight of study conduct, but all data analyses and interpretation were completed independent of the funding agencies. We are indebted to our medical and nursing colleagues and the infants and their parents who agreed to take part in this study. NR 72 TC 14 Z9 14 U1 0 U2 7 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0735-1631 J9 AM J PERINAT JI Am. J. Perinatol. PD OCT PY 2010 VL 27 IS 9 BP 721 EP 730 DI 10.1055/s-0030-1253555 PG 10 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 658XR UT WOS:000282528500008 PM 20408111 ER PT J AU Incerti, M Vink, J Roberson, R Abebe, D Spong, CY AF Incerti, Maddalena Vink, Joy Roberson, Robin Abebe, Daniel Spong, Catherine Y. TI Treatment with Neuropeptides Attenuates c-fos Expression in a Mouse Model of Fetal Alcohol Syndrome SO AMERICAN JOURNAL OF PERINATOLOGY LA English DT Article DE Fetal alcohol syndrome (FAS); c-fos; oxidative stress; NAPVSIPQ (NAP); SALLRSIPA (SAL) ID VASOACTIVE-INTESTINAL-PEPTIDE; DEPENDENT NEUROTROPHIC FACTOR; IMMEDIATE-EARLY GENE; NEUROPROTECTIVE PEPTIDE; LEARNING-DEFICITS; OXIDATIVE STRESS; HIPPOCAMPUS; RAT; MEMORY; NEUROTOXICITY AB Fetal alcohol syndrome (FAS) is the most common nongenetic cause of mental retardation and is characterized by neurodevelopmental anomalies. C-fos is a cellular marker of transcriptional activity in the stress-signal pathway. Previously, we showed the treatment with NAP (NAPVSIPQ) + SAL (SALLRSIPA) reversed the learning deficit after prenatal alcohol exposure in FAS. Our objective was to evaluate if the mechanism of actions of NAP + SAL involves the stress-signal pathway differentiating c-fos expression in mouse brains after prenatal alcohol exposure. C57Bl6/J mice were treated with alcohol (0.03 mL/g) or placebo on gestational day 8. On postnatal day 40, in utero alcohol-exposed males were treated via gavage with 40 mu g D-NAP and 40 mu g D-SAL (n = 6) or placebo (n = 4); controls were gavaged with placebo daily (n = 12). After learning evaluation, hippocampus, cerebellum, and cortex were isolated. Calibrator-normalized relative realtime polymerase chain reaction and Western blot analysis were performed. Statistics included analysis of variance and post hoc Fisher analysis. Adult treatment with NAP + SAL restored the down-regulation of c-fos in the hippocampus after prenatal alcohol exposure (p < 0.05), but not in the cerebellum. There was no difference in c-fos expression in the cortex. Adult treatment with NAP + SAL restored the down-regulation of c-fos expression in hippocampus attenuating the alcohol-induced alteration of the stress-signal pathway. C1 [Incerti, Maddalena; Vink, Joy; Roberson, Robin; Abebe, Daniel; Spong, Catherine Y.] Eunice Kennedy Shriver NICHD, NIH, Unit Perinatal & Dev Neurobiol, Bethesda, MD 20892 USA. [Incerti, Maddalena] Univ Milano Bicocca, Dept Obstet & Gynecol, Monza, Italy. [Vink, Joy] Columbia Univ, Med Ctr, Div Maternal Fetal Med, New York, NY USA. RP Incerti, M (reprint author), Eunice Kennedy Shriver NICHD, NIH, Unit Perinatal & Dev Neurobiol, Bldg 9 Room 1W125,9 Mem Dr, Bethesda, MD 20892 USA. EM maddalena.incerti@gmail.com FU DIR of Eunice Kennedy Shriver National Institute of Child Health and Human Development FX The research was supported by the DIR of Eunice Kennedy Shriver National Institute of Child Health and Human Development. NR 30 TC 2 Z9 2 U1 1 U2 4 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0735-1631 J9 AM J PERINAT JI Am. J. Perinatol. PD OCT PY 2010 VL 27 IS 9 BP 743 EP 748 DI 10.1055/s-0030-1253558 PG 6 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 658XR UT WOS:000282528500011 PM 20446212 ER PT J AU Shoemaker, LL Lenker, JA Fuhrer, MJ Jutai, JW Demers, L DeRuyter, F AF Shoemaker, Laura L. Lenker, James A. Fuhrer, Marcus J. Jutai, Jeffrey W. Demers, Louise DeRuyter, Frank TI Development and Evaluation of a New Taxonomy of Mobility-Related Assistive Technology Devices SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Article DE Assistive Technology Devices; Taxonomy; Outcomes Research; Mobility Research ID BLACK-BOX; REHABILITATION; OUTCOMES AB Shoemaker LL, Lenker JA, Fuhrer MJ, Jutai JW, Demers L, DeRuyter F: Development and evaluation of a new taxonomy of mobility-related assistive technology devices. Am J Phys Med Rehabil 2010; 89:795-808. Objective: This article reports on the development of a new taxonomy for mobility-related assistive technology devices. Design: A prototype taxonomy was created based on the extant literature. Five mobility device experts were engaged in a modified Delphi process to evaluate and refine the taxonomy. Results: Multiple iterations of expert feedback and revision yielded consensual agreement on the structure and terminology of a new mobility device taxonomy. The taxonomy uses a hierarchical framework to classify ambulation aids and wheeled mobility devices, including their key features that impact mobility. Five attributes of the new taxonomy differentiate it from previous mobility-related device classifications: (1) hierarchical structure, (2) primary device categories are grouped based on their intended mobility impact, (3) comprehensive inclusion of technical features, (4) a capacity to assimilate reimbursement codes, and (5) availability of a detailed glossary. Conclusions: The taxonomy is intended to support assistive technology outcomes research. The taxonomy will enable researchers to capture mobility-related assistive technology device interventions with precision and provide a common terminology that will allow comparisons among studies. The prominence of technical features within the new taxonomy will hopefully promote research that helps clinicians predict how devices will perform, thus aiding clinical decision making and supporting funding recommendations. C1 [Lenker, James A.] SUNY Buffalo, Dept Rehabil Sci, Sch Publ Hlth & Hlth Profess, Buffalo, NY 14214 USA. [Shoemaker, Laura L.] Wascana Rehabil Ctr, Adult Program, Regina, SK, Canada. [Fuhrer, Marcus J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 21046 USA. [Jutai, Jeffrey W.] Univ Ottawa, Interdisciplinary Sch Hlth Sci, Ottawa, ON, Canada. [Demers, Louise] Univ Montreal, Fac Med, Montreal Geriatr Univ Inst, Res Ctr, Montreal, PQ H3C 3J7, Canada. [Demers, Louise] Univ Montreal, Fac Med, Sch Rehabil, Montreal, PQ H3C 3J7, Canada. [DeRuyter, Frank] Duke Univ, Med Ctr, Dept Surg, Div Speech Pathol & Audiol, Durham, NC 27710 USA. RP Lenker, JA (reprint author), SUNY Buffalo, Dept Rehabil Sci, Sch Publ Hlth & Hlth Profess, 515 Kimball Tower,3435 Main St, Buffalo, NY 14214 USA. OI Jutai, Jeffrey/0000-0002-7294-1323 FU National Institute on Disability and Rehabilitation Research (NIDRR) [H133A060062] FX This work was supported in part by the National Institute on Disability and Rehabilitation Research (NIDRR) under Grant #H133A060062. A portion of this material was presented at the 2009 International Seating Symposium, March 11-14, 2009, Orlando, Florida. Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article. NR 26 TC 2 Z9 2 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0894-9115 J9 AM J PHYS MED REHAB JI Am. J. Phys. Med. Rehabil. PD OCT PY 2010 VL 89 IS 10 BP 795 EP 808 DI 10.1097/PHM.0b013e3181f1bbcd PG 14 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 652XA UT WOS:000282043600002 PM 20855980 ER PT J AU Zhang, Y Cao, CM Xiao, RP AF Zhang, Yan Cao, Chun-Mei Xiao, Rui-Ping TI Kinase activity-independent anchoring function of protein kinase C-delta. Focus on "Protein kinase C-delta regulates the subcellular localization of Shc in H2O2-treated cardiomyocytes" SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article ID PROTEOLYTIC ACTIVATION; PKC-DELTA; CELLS; APOPTOSIS; EPSILON; HEART; RAT; PROTECTION; ISOFORMS; ISOTYPES C1 [Xiao, Rui-Ping] NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. [Zhang, Yan; Cao, Chun-Mei; Xiao, Rui-Ping] Peking Univ, Inst Mol Med, Beijing 100871, Peoples R China. [Xiao, Rui-Ping] Peking Univ, Ctr Drug Discovery, Sch Chem Biol & Biotechnol, Shenzhen Grad Sch, Shenzhen, Peoples R China. RP Xiao, RP (reprint author), NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM xiaor@mail.nih.gov RI Zhang, Yan/B-2831-2012 NR 32 TC 0 Z9 0 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD OCT PY 2010 VL 299 IS 4 BP C733 EP C735 DI 10.1152/ajpcell.00301.2010 PG 3 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 653YE UT WOS:000282133500004 PM 20686076 ER PT J AU Berglund, ED Kang, L Lee-Young, RS Hasenour, CM Lustig, DG Lynes, SE Donahue, EP Swift, LL Charron, MJ Wasserman, DH AF Berglund, Eric D. Kang, Li Lee-Young, Robert S. Hasenour, Clinton M. Lustig, Daniel G. Lynes, Sara E. Donahue, E. Patrick Swift, Larry L. Charron, Maureen J. Wasserman, David H. TI Glucagon and lipid interactions in the regulation of hepatic AMPK signaling and expression of PPAR alpha and FGF21 transcripts in vivo(Retracted article. See vol.311,pg.E850,2016) SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article; Retracted Publication DE adenosine 5 '-monophosphate-activated protein kinase; peroxisome proliferator-activated receptor-alpha; fibroblast growth factor 21 ID ACTIVATED PROTEIN-KINASE; ACETYL-COA CARBOXYLASE; GLUCOSE-METABOLISM; FATTY-ACIDS; INSULIN SENSITIVITY; PROLONGED EXERCISE; ENERGY-STATE; SHORT-TERM; RAT-LIVER; MICE AB Berglund ED, Kang L, Lee-Young RS, Hasenour CM, Lustig DG, Lynes SE, Donahue EP, Swift LL, Charron MJ, Wasserman DH. Glucagon and lipid interactions in the regulation of hepatic AMPK signaling and expression of PPAR alpha and FGF21 transcripts in vivo. Am J Physiol Endocrinol Metab 299: E607-E614, 2010. First published July 27, 2010; doi: 10.1152/ajpendo.00263.2010.-Hepatic glucagon action increases in response to accelerated metabolic demands and is associated with increased whole body substrate availability, including circulating lipids. The hypothesis that increases in hepatic glucagon action stimulate AMP-activated protein kinase (AMPK) signaling and peroxisome proliferator-activated receptor-alpha (PPAR alpha) and fibroblast growth factor 21 (FGF21) expression in a manner modulated by fatty acids was tested in vivo. Wild-type (gcgr(+/+)) and glucagon receptor-null (gcgr(-/-)) littermate mice were studied using an 18-h fast, exercise, and hyperglucagonemic-euglycemic clamps plus or minus increased circulating lipids. Fasting and exercise in gcgr(+/+), but not gcgr(-/-) mice, increased hepatic phosphorylated AMPK alpha at threonine 172 (p-AMPK(Thr172)) and PPAR alpha and FGF21 mRNA. Clamp results in gcgr(+/+) mice demonstrate that hyperlipidemia does not independently impact or modify glucagon-stimulated increases in hepatic AMP/ATP, p-AMPK(Thr172), or PPAR alpha and FGF21 mRNA. It blunted glucagon-stimulated acetyl-CoA carboxylase phosphorylation, a downstream target of AMPK, and accentuated PPAR alpha and FGF21 expression. All effects were absent in gcgr(-/-) mice. These findings demonstrate that glucagon exerts a critical regulatory role in liver to stimulate pathways linked to lipid metabolism in vivo and shows for the first time that effects of glucagon on PPAR alpha and FGF21 expression are amplified by a physiological increase in circulating lipids. C1 [Berglund, Eric D.; Kang, Li; Lee-Young, Robert S.; Hasenour, Clinton M.; Lustig, Daniel G.; Lynes, Sara E.; Donahue, E. Patrick; Wasserman, David H.] Vanderbilt Univ, Sch Med, Dept Mol Physiol & Biophys, Nashville, TN 37212 USA. [Swift, Larry L.] Vanderbilt Univ, Sch Med, Dept Pathol, Nashville, TN 37212 USA. [Wasserman, David H.] Vanderbilt Univ, Sch Med, NIH, Mouse Metab Phenotyping Ctr, Nashville, TN 37212 USA. [Charron, Maureen J.] Albert Einstein Coll Med, Dept Biochem, Brooklyn, NY USA. RP Wasserman, DH (reprint author), 823 Light Hall, Nashville, TN 37232 USA. EM david.wasserman@vanderbilt.edu FU National Institute of Diabetes and Digestive and Kidney Diseases [DK-50277, DK-59637]; National Institutes of Health [DK-07563] FX This work was supported by National Institute of Diabetes and Digestive and Kidney Diseases Grants DK-50277 and DK-59637 to D. H. Wasserman. E. D. Berglund was supported by an National Institutes of Health T32 Molecular Endocrinology Training Program Grant (DK-07563 awarded to R. O'Brien). NR 51 TC 52 Z9 54 U1 1 U2 6 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 EI 1522-1555 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD OCT PY 2010 VL 299 IS 4 BP E607 EP E614 DI 10.1152/ajpendo.00263.2010 PG 8 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 673MF UT WOS:000283666700011 PM 20663988 ER PT J AU Matsumoto, T Hess, S Kajiyama, H Sakairi, T Saleem, MA Mathieson, PW Nojima, Y Kopp, JB AF Matsumoto, Takayuki Hess, Sonja Kajiyama, Hiroshi Sakairi, Toru Saleem, Moin A. Mathieson, Peter W. Nojima, Yoshihisa Kopp, Jeffrey B. TI Proteomic analysis identifies insulin-like growth factor-binding protein-related protein-1 as a podocyte product SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE proteomics; secretory protein; human immunodeficiency virus-associated nephropathy ID EPITHELIAL-CELLS; GLOMERULAR PODOCYTES; BREAST-CANCER; EXPRESSION; IGFBP-RP1; MAC25; GLOMERULOSCLEROSIS; PROGRESSION; SENESCENCE; APOPTOSIS AB Matsumoto T, Hess S, Kajiyama H, Sakairi T, Saleem MA, Mathieson PW, Nojima Y, Kopp JB. Proteomic analysis identifies insulin-like growth factor-binding protein-related protein-1 as a podocyte product. Am J Physiol Renal Physiol 299: F776-F784, 2010. First published July 14, 2010; doi:10.1152/ajprenal.00597.2009.-The podocyte secretory proteome may influence the phenotype of adjacent podocytes, endothelial cells, parietal epithelial cells, and tubular epithelial cells but has not been systematically characterized. We have initiated studies to characterize this proteome, with the goal of further understanding the podocyte cell biology. We cultured differentiated conditionally immortalized human podocytes and subjected the proteins in conditioned medium to mass spectrometry. At a false discovery rate of <3%, we identified 111 candidates from conditioned medium, including 44 proteins that have signal peptides or are described as secreted proteins in the UniProt database. As validation, we confirmed that one of these proteins, insulin-like growth factor-binding protein-related protein-1 (IGFBP-rP1), was expressed in mRNA and protein of cultured podocytes. In addition, transforming growth factor-beta 1 stimulation increased IGFBP-rP1 in conditioned medium. We analyzed IGFBP-rP1 glomerular expression in a mouse model of human immunodeficiency virus-associated nephropathy. IGFBP-rP1 was absent from podocytes of normal mice and was expressed in podocytes and pseudocrescents of transgenic mice, where it was coexpressed with desmin, a podocyte injury marker. We conclude that IGFBP-rP1 may be a product of injured podocytes. Further analysis of the podocyte secretory proteome may identify biomarkers of podocyte injury. C1 [Matsumoto, Takayuki; Kajiyama, Hiroshi; Sakairi, Toru; Kopp, Jeffrey B.] NIDDK, Kidney Dis Sect, Kidney Dis Branch, NIH,US Dept HHS, Bethesda, MD USA. [Hess, Sonja] NIDDK, Prote & Mass Spectrometry Facil, NIH, US Dept HHS, Bethesda, MD USA. [Matsumoto, Takayuki; Nojima, Yoshihisa] Gunma Univ, Grad Sch Med, Dept Med & Clin Sci, Gunma, Japan. [Saleem, Moin A.; Mathieson, Peter W.] Univ Bristol, Childrens Renal Unit, Bristol, Avon, England. [Saleem, Moin A.; Mathieson, Peter W.] Univ Bristol, Acad Renal Unit, Bristol, Avon, England. RP Kopp, JB (reprint author), 10 Ctr Dr, Bethesda, MD 20892 USA. EM jbkopp@nih.gov RI Hess, Sonja/K-4842-2013; OI Hess, Sonja/0000-0002-5904-9816; Kopp, Jeffrey/0000-0001-9052-186X FU National Institute of Diabetes and Digestive and Kidney Diseases FX This work was supported by the National Institute of Diabetes and Digestive and Kidney Diseases Intramural Research Program. NR 36 TC 7 Z9 7 U1 2 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD OCT PY 2010 VL 299 IS 4 BP F776 EP F784 DI 10.1152/ajprenal.00597.2009 PG 9 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 658IP UT WOS:000282484000011 PM 20630940 ER PT J AU Sakairi, T Abe, Y Jat, PS Kopp, JB AF Sakairi, Toru Abe, Yoshifusa Jat, Parmijit S. Kopp, Jeffrey B. TI Cell-cell contact regulates gene expression in CDK4-transformed mouse podocytes SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE cyclin-dependent kinase 4; SV40 large T antigen; nephrin; synaptopodin; Wilms tumor-1; P-cadherin ID LARGE-T-ANTIGEN; EPITHELIAL-CELLS; LINES; NEPHRIN; SIMIAN-VIRUS-40; IMMORTALIZATION; TRANSCRIPTION; TEMPERATURE; PATHWAY; DISEASE AB Sakairi T, Abe Y, Jat PS, Kopp JB. Cell-cell contact regulates gene expression in CDK4-transformed mouse podocytes. Am J Physiol Renal Physiol 299: F802-F809, 2010. First published July 28, 2010; doi:10.1152/ajprenal.00205.2010.-We transformed mouse podocytes by ectopic expression of cyclin-dependent kinase 4 (CDK4). Compared with podocytes transformed with a thermo-sensitive SV40 large T antigen mutant tsA58U19 (tsT podocytes), podocytes transformed with CDK4 (CDK4 podocytes) exhibited significantly higher expression of nephrin mRNA. Synaptopodin mRNA expression was significantly lower in CDK4 podocytes and in tsT podocytes under growth-permissive conditions (33 degrees C) compared with tsT podocytes under growth-restricted conditions (37 degrees C), which suggests a role for cell cycle arrest in synaptopodin mRNA expression. Confluent CDK4 podocytes showed significantly higher mRNA expression levels for nephrin, synaptopodin, Wilms tumor 1, podocalyxin, and P-cadherin compared with subconfluent cultures. We carried out experiments to clarify roles of various factors in the confluent podocyte cultures; our findings indicate that cell-cell contact promotes expression of five podocyte marker genes studied, that cellular quiescence increases synaptopodin and podocalyxin mRNA expression, and that soluble factors play a role in nephrin mRNA expression. Our findings suggest that CDK4 podocytes are useful tools to study podocyte biology. Furthermore, the role of cell-cell contact in podocyte gene expression may have relevance for podocyte function in vivo. C1 [Kopp, Jeffrey B.] NIDDKD, Kidney Dis Sect, Kidney Dis Branch, NIH, Bethesda, MD 20892 USA. [Jat, Parmijit S.] UCL, Inst Neurol, Dept Neurodegenerat Dis, London, England. RP Kopp, JB (reprint author), NIDDKD, Kidney Dis Sect, Kidney Dis Branch, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA. EM jbkopp@nih.gov OI Kopp, Jeffrey/0000-0001-9052-186X FU National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health [ZO1-DK-043308] FX This study was supported by Intramural Research Program, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health under Grant ZO1-DK-043308. NR 32 TC 4 Z9 4 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD OCT PY 2010 VL 299 IS 4 BP F802 EP F809 DI 10.1152/ajprenal.00205.2010 PG 8 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 658IP UT WOS:000282484000014 PM 20668098 ER PT J AU Angst, J Cui, LH Swendsen, J Rothen, S Cravchik, A Merikangas, KR AF Angst, Jules Cui, Lihong Swendsen, Joel Rothen, Stephane Cravchik, Anibal Merikangas, Kathleen R. TI Major Depressive Disorder With Subthreshold Bipolarity in the National Comorbidity Survey Replication SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID WORLD-HEALTH-ORGANIZATION; SPECTRUM DISORDERS; PRIVATE-PRACTICE; RATING-SCALE; II-DISORDER; NCS-R; PREVALENCE; VALIDITY; VERSION; MANIA AB Objective: There is growing clinical and epidemiologic evidence that major mood disorders form a spectrum from major depressive disorder to pure mania. The authors examined the prevalence and clinical correlates of major depressive disorder with subthreshold bipolarity compared with pure major depressive disorder in the National Comorbidity Survey Replication (NCS-R). Method: The NCS-R is a nationally representative face-to-face household survey of the U.S. population conducted between February 2001, and April 2003. Lifetime history of mood disorders, symptoms, and clinical indicators of severity were collected using version 3.0 of the World Health Organization's Composite International Diagnostic Interview. Results: Nearly 40% of study participants with a history of major depressive disorder had a history of subthreshold hypomania. This subgroup had a younger age at onset, more episodes of depression, and higher rates of comorbidity than those without a history of hypomania and lower levels of clinical severity than those with bipolar II disorder. Conclusions: These findings demonstrate heterogeneity in major depressive disorder and support the validity of inclusion of subthreshold mania in the diagnostic classification. The broadening of criteria for bipolar disorder would have important implications for research and clinical practice. C1 [Merikangas, Kathleen R.] NIMH, Intramural Res Program, Genet Epidemiol Res Branch, Bethesda, MD 20892 USA. Zurich Univ Psychiat Hosp, Dept Psychiat, Zurich, Switzerland. Natl Sci Res Ctr CNRS 5231, Bordeaux, France. Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. Univ Hosp Ctr, Dept Psychiat, Lausanne, Switzerland. Univ Lausanne, Lausanne, Switzerland. Univ Hosp Geneva, Dept Psychiat, Geneva, Switzerland. RP Merikangas, KR (reprint author), NIMH, Intramural Res Program, Genet Epidemiol Res Branch, 35 Convent Dr,MSC 3720, Bethesda, MD 20892 USA. EM merikank@mail.nih.gov RI Rothen, Stephane/E-8325-2014 OI Rothen, Stephane/0000-0003-3891-277X FU Bristol-Myers Squibb; Eli Lilly; GlaxoSmithKline; Johnson & Johnson Pharmaceuticals; Ortho-McNeil; Pfizer; Sanofi-Aventis; NIMH [U01-MH60220]; National Institute of Drug Abus; Substance Abuse and Mental Health Services Administration; Robert Wood Johnson Foundation [044708]; John W. Alden Trust; French National Center for Scientific Research FX Dr. Kessler has served in an advisory or consulting capacity for Eli Lilly, GlaxoSmithKline, Kaiser Permanente, Pfizer, Sanofi-Aventis, Shire, and Wyeth-Ayerst and has received research support for epidemiological studies from Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Johnson & Johnson Pharmaceuticals, Ortho-McNeil, Pfizer, and Sanofi-Aventis. Dr. Angst has served in advisory or speaking capacities for AstraZeneca, Eli Lilly, Janssen Cilag, and Sanofi-Aventis.; The National Comorbidity Survey Replication was supported by NIMH grant U01-MH60220 with supplemental support from the National Institute of Drug Abuse; the Substance Abuse and Mental Health Services Administration; grant 044708 from the Robert Wood Johnson Foundation; and the John W. Alden Trust. Manuscript preparation was supported by NIMH's Intramural Research Program (for Ms. Cui and Drs. Cravchik, Rothen, and Merikangas) and an ATIP award (to Dr. Swendsen) from the French National Center for Scientific Research. NR 39 TC 159 Z9 160 U1 4 U2 17 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD OCT PY 2010 VL 167 IS 10 BP 1194 EP 1201 DI 10.1176/appi.ajp.2010.09071011 PG 8 WC Psychiatry SC Psychiatry GA 656XP UT WOS:000282374700011 PM 20713498 ER PT J AU Hasler, G van der Veen, JW Grillon, C Drevets, WC Shen, J AF Hasler, Gregor van der Veen, Jan Willem Grillon, Christian Drevets, Wayne C. Shen, Jun TI Effect of Acute Psychological Stress on Prefrontal GABA Concentration Determined by Proton Magnetic Resonance Spectroscopy SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID AMINOBUTYRIC-ACID LEVELS; CEREBRAL-BLOOD-FLOW; PANIC DISORDER; SOMATOSENSORY CORTEX; RECEPTOR-BINDING; CORTICAL GABA; MOUSE BRAIN; IN-VIVO; RATS; TRANSAMINASE AB Objective: Impaired function of the central gamma-aminobutyric acid (GABA) system, which provides the brain's major inhibitory pathways, is thought to play an important role in the pathophysiology of anxiety disorders. The effect of acute psychological stress on the human GABA-ergic system is still unknown, however. The purpose of this study was to determine the effect of acute stress on prefrontal GABA levels. Method: A recently developed noninvasive magnetic resonance spectroscopy method was used to measure changes in the GABA concentration of the prefrontal cortex in 10 healthy human subjects during a threat-of-shock condition and during a safe condition (two sessions on different days). The main outcome measure was the mean GABA concentration within a 3x3x2-cm(3) voxel selected from the medial prefrontal cortex. Results: Prefrontal GABA decreased by approximately 18% in the threat-of-shock condition relative to the safe condition. This reduction was specific to GABA, since the concentrations of N-acetyl-aspartate, choline-containing compounds, and glutamate/glutamine levels obtained in the same spectra did not change significantly. Conclusions: This result appeared compatible with evidence from preclinical studies in rodents, which showed rapid presynaptic down-regulation of GABAergic neurotransmission in response to acute psychological stress. The molecular mechanism and functional significance of this reduced inhibitory effect of acute psychological stress in relation to impaired GABA-ergic function in anxiety disorders merit further investigation. C1 [Hasler, Gregor] Univ Bern, Psychiat Univ Hosp, CH-3000 Bern 60, Switzerland. NIMH, Sect Neuroimaging Mood & Anxiety Disorders, Bethesda, MD 20892 USA. NIMH, Sect Magnet Resonance Spectroscopy, Bethesda, MD 20892 USA. RP Hasler, G (reprint author), Univ Bern, Psychiat Univ Hosp, Bolligenstr 111, CH-3000 Bern 60, Switzerland. EM g.hasler@bluewin.ch RI Hasler, Gregor/E-4845-2012 OI Hasler, Gregor/0000-0002-8311-0138 FU Intramural NIH HHS [ZIA MH002798-09] NR 41 TC 38 Z9 39 U1 1 U2 7 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD OCT PY 2010 VL 167 IS 10 BP 1226 EP 1231 DI 10.1176/appi.ajp.2010.09070994 PG 6 WC Psychiatry SC Psychiatry GA 656XP UT WOS:000282374700015 PM 20634372 ER PT J AU Resnik, DB AF Resnik, David B. TI Urban Sprawl, Smart Growth, and Deliberative Democracy SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID BUILT ENVIRONMENT; PHYSICAL-ACTIVITY; PUBLIC-HEALTH; OBESITY AB Urban sprawl is an increasingly common feature of the built environment in the United States and other industrialized nations. Although there is considerable evidence that urban sprawl has adverse affects on public health and the environment, policy frameworks designed to combat sprawl-such as smart growth-have proven to be controversial, making implementation difficult. Smart growth has generated considerable controversy because stakeholders affected by urban planning policies have conflicting interests and divergent moral and political viewpoints. In some of these situations, deliberative democracy-an approach to resolving controversial public-policy questions that emphasizes open, deliberative debate among the affected parties as an alternative to voting-would be a fair and effective way to resolve urban-planning issues. (Am J Public Health. 2010;100: 1852-1856. doi:10.2105/AJPH.2009.182501) C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. RP Resnik, DB (reprint author), NIEHS, NIH, Box 12233,Mail Drop CU 03, Res Triangle Pk, NC 27709 USA. EM resnikd@niehs.nih.gov FU National Institute for Environmental Health Sciences, National Institutes of Health FX This research was supported by the Intramural Program of the National Institute for Environmental Health Sciences, National Institutes of Health. NR 42 TC 6 Z9 6 U1 2 U2 21 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD OCT PY 2010 VL 100 IS 10 BP 1852 EP 1856 DI 10.2105/AJPH.2009.182501 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 656SC UT WOS:000282355900011 PM 20724685 ER PT J AU Roth, GA Fee, E AF Roth, Ginny A. Fee, Elizabeth TI A Soldier's Hero: Edith Cavell (1865-1915) SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Biographical-Item C1 [Roth, Ginny A.; Fee, Elizabeth] NIH, Hist Med Div, Natl Lib Med, Bethesda, MD 20894 USA. RP Roth, GA (reprint author), NIH, Hist Med Div, Natl Lib Med, 8600 Rockville Pike,MSC 3819,Bldg 38,Room 1E21, Bethesda, MD 20894 USA. EM ginny.roth@nih.gov NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD OCT PY 2010 VL 100 IS 10 BP 1865 EP 1866 DI 10.2105/AJPH.2009.188599 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 656SC UT WOS:000282355900015 PM 20724678 ER PT J AU Prevots, DR Shaw, PA Strickland, D Jackson, LA Raebel, MA Blosky, MA de Oca, RM Shea, YR Seitz, AE Holland, SM Olivier, KN AF Prevots, D. Rebecca Shaw, Pamela A. Strickland, Daniel Jackson, Lisa A. Raebel, Marsha A. Blosky, Mary Ann de Oca, Ruben Montes Shea, Yvonne R. Seitz, Amy E. Holland, Steven M. Olivier, Kenneth N. TI Nontuberculous Mycobacterial Lung Disease Prevalence at Four Integrated Health Care Delivery Systems SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE epidemiology; prevalence; nontuberculous mycobacteria; atypical mycobacteria ID AVIUM-COMPLEX; UNITED-STATES; HIV-INFECTION; CLARITHROMYCIN; EPIDEMIOLOGY AB Rationale: Single-site clinic-based studies suggest an increasing prevalence of pulmonary nontuberculous mycobacteria (NTM) disease, but systematic data are lacking. Objectives: To describe prevalence and trends for NTM lung disease at four geographically diverse integrated heath care delivery systems in the United States. Methods: We abstracted mycobacterial culture results from electronic laboratory databases and linked to other datasets containing clinical and demographic information. Possible cases were defined as a single positive NTM pulmonary isolate, and definite cases were defined as two positive sputum cultures, or one positive culture from a bronchoalveolar lavage or lung biopsy. Annual prevalence was calculated using United States census data; average annual prevalence is presented for 2004-2006. Poisson regression models were used to estimate the annual percent change in prevalence. Measurements and Main Results: A total of 28,697 samples from 7,940 patients were included in the analysis. Of these, 3,988 (50%) were defined as possible cases, and 1,865 (47%) of these were defined as definite cases. Average annual (2004-2006) site-specific prevalence ranged from 1.4 to 6.6 per 100,000. Prevalence was 1.1- to 1.6-fold higher among women relative to men across sites. The prevalence of NTM lung disease was increasing significantly at the two sites where trends were studied, by 2.6% per year among women and 2.9% per year among men. Among persons aged greater than or equal to 60 years, annual prevalence increased from 19.6 per 100,000 during 1994-1996 to 26.7 per 100,000 during 2004-2006. Conclusions: The epidemiology of nontuberculous mycobacterial lung disease is changing, with a predominance of women and increasing prevalence at the sites studied. C1 [Prevots, D. Rebecca; de Oca, Ruben Montes; Seitz, Amy E.; Holland, Steven M.; Olivier, Kenneth N.] NIAID, NIH, Lab Clin Infect Dis, Bethesda, MD 20892 USA. [Shaw, Pamela A.] NIAID, NIH, Biostat Res Branch, Bethesda, MD 20892 USA. [Strickland, Daniel] Kaiser Permanente So Calif, Res & Evaluat Unit, Pasadena, CA USA. [Jackson, Lisa A.] Grp Hlth Res Inst, Grp Hlth, Seattle, WA USA. [Raebel, Marsha A.] Kaiser Permanente Colorado, Inst Hlth Res, Denver, CO USA. [Blosky, Mary Ann] Geisinger Hlth Syst, Geisinger Ctr Hlth Res, Danville, PA USA. [de Oca, Ruben Montes] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA. RP Prevots, DR (reprint author), NIAID, NIH, Lab Clin Infect Dis, Qrtrs 15B-1,8 West Dr,MSC 2665, Bethesda, MD 20892 USA. EM rprevots@niaid.nih.gov FU National Institute of Allergy and Infectious Diseases, National Institutes of Health; NTM Info and Research; Sanofi-Aventis; NIH; Wyeth; Novartis; GlaxoSmithKline; Sanofi Pasteur; Centers for Disease Control and Prevention; ICON FX Supported in part by the Intramural Research Program of the National Institute of Allergy and Infectious Diseases, National Institutes of Health, and by a grant from NTM Info and Research, a 501C3 nonprofit organization devoted to pulmonary nontuberculous mycobacteria disease.; D.R.P. is an employee of the National Institutes of Health (NIH). P.A.S. is an employee of the NIH. D.S. is a full-time employee of the Southern California Permanente Medical Group, and received more than $100,001 from Sanofi-Aventis in industry-sponsored grants for the study of diabetes medications and cancer risk and $5,000 in contract funds from the NIH. L.A.J. received $10,001-$50,000 from Wyeth, $5,001-$10,000 from Novartis, and $1,001-$5,000 from GlaxoSmithKline in consultancy fees; more than $100,001 from Wyeth, more than $100,001 from Sanofi Pasteur, more than $100,001 from Novartis, and more than $100,001 from GlaxoSmithKline in industry-sponsored grants; and more than $100,001 from the NIH and more than $100,001 from the Centers for Disease Control and Prevention in sponsored grants. M.A.R.'s primary employer is the Kaiser Foundation Health Plan of Colorado and received $50,001-$100,000 from ICON in industry-sponsored grants for a research project on Clostridium difficile prevalence. M.A.B. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. R.M.D.O. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. Y.R.S. is employed by the NIH as a Microbiologist at NIH/DLM/Micro service. A.E.S. is employed by the NIH as a contractor through Kelly Services. S.M.H. is an employee of the NIH. K.N.O. is an employee of the NIH. NR 24 TC 163 Z9 168 U1 1 U2 5 PU AMER THORACIC SOC PI NEW YORK PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD OCT 1 PY 2010 VL 182 IS 7 BP 970 EP 976 DI 10.1164/rccm.201002-0310OC PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 660UZ UT WOS:000282673200018 PM 20538958 ER PT J AU Bluemke, DA AF Bluemke, David A. TI MRI of Nonischemic Cardiomyopathy SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE arrhythmogenic right ventricular dysplasia; cardiomyopathy; hypertrophic cardiomyopathy; MRI; myocardium ID CARDIOVASCULAR MAGNETIC-RESONANCE; RIGHT-VENTRICULAR DYSPLASIA; HYPERTROPHIC CARDIOMYOPATHY; HEART-FAILURE; FAT DETECTION; DIAGNOSIS; DYSPLASIA/CARDIOMYOPATHY; ENHANCEMENT; MANAGEMENT; ARRHYTHMIA AB OBJECTIVE. The purpose of this article is to present current clinical and research issues in MRI evaluation of nonischemic cardiomyopathy, a diverse set of diseases, many of which have a genetic basis. CONCLUSION. Cardiac cine MRI along with delayed myocardial enhancement MRI and other MRI techniques can provide information beyond echocardiography for tissue characterization. MRI is increasingly being used for evaluation of genetically positive, phenotypically negative patients as well as for risk stratification. C1 Natl Inst Biomed Imaging & Bioengn, NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Bluemke, DA (reprint author), Natl Inst Biomed Imaging & Bioengn, NIH, Ctr Clin, 10 Ctr Dr,Room 1C 355, Bethesda, MD 20892 USA. EM bluemked@nih.gov OI Bluemke, David/0000-0002-8323-8086 FU Intramural NIH HHS [ZIA EB000072-01] NR 26 TC 11 Z9 12 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD OCT PY 2010 VL 195 IS 4 BP 935 EP 940 DI 10.2214/AJR.10.4222 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 652TU UT WOS:000282033600021 PM 20858821 ER PT J AU Shao, HP Xi, LQ Raffeld, M Pittaluga, S Dunleavy, K Wilson, WH Spector, N Milito, C Morais, JC Jaffe, ES AF Shao, Haipeng Xi, Liqiang Raffeld, Mark Pittaluga, Stefania Dunleavy, Kieron Wilson, Wyndham H. Spector, Nelson Milito, Cristiane Morais, Jose Carlos Jaffe, Elaine S. TI Nodal and Extranodal Plasmacytomas Expressing Immunoglobulin A An Indolent Lymphoproliferative Disorder With a Low Risk of Clinical Progression SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE extramedullary plasmacytoma; IgA; lymph node; plasma cell myeloma ID B-CELL LYMPHOMA; SYSTEMIC-LUPUS-ERYTHEMATOSUS; GROWTH-FACTOR-BETA; MULTIPLE-MYELOMA; EXTRAMEDULLARY PLASMACYTOMA; CASTLEMANS-DISEASE; SOLITARY PLASMACYTOMA; DIFFERENTIATION; HYPERPLASIA; BONE AB Plasmacytomas expressing immunoglobulin A are rare and not well characterized. In this study, 9 cases of IgA-positive plasmacytoma presenting in lymph node and 3 in extranodal sites were analyzed by morphology, immunohistochemistry, and polymerase chain reaction examination of immunoglobulin heavy and kappa light chain genes. Laboratory features were correlated with clinical findings. There were 7 males and 5 females; age range was 10 to 66 years (median, 32 y). Six of the patients were younger than 30 years of age, 5 of whom had nodal disease. About 67% (6 of 9) of the patients with nodal disease had evidence of immune system dysfunction, including human immunodeficiency virus infection, T-cell deficiency, autoantibodies, arthritis, Sjogren syndrome, and decreased B cells. An IgA M-spike was detected in 6 of 11 cases, and the M-protein was nearly always less than 30 g/L. All patients had an indolent clinical course without progression to plasma cell myeloma. Histologically, nodal IgA plasmacytomas showed an interfollicular or diffuse pattern of plasma cell infiltration. The plasma cells were generally of mature Marschalko type with little or mild pleomorphism and exclusive expression of monotypic IgA. There was an equal expression of kappa and lambda light chains (ratio 6: 6). Clonality was showed in 9 of 12 cases: by polymerase chain reaction in 7 cases, by cytogenetic analysis in 1 case, and by immunofixation in 1 case. Clonality did not correlate with pattern of lymph node infiltration. Our results suggest that IgA plasmacytomas may represent a distinct form of extramedullary plasmacytoma characterized by younger age at presentation, frequent lymph node involvement, and low risk of progression to plasma cell myeloma. C1 [Shao, Haipeng; Xi, Liqiang; Raffeld, Mark; Pittaluga, Stefania; Dunleavy, Kieron; Wilson, Wyndham H.; Jaffe, Elaine S.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Shao, Haipeng; Xi, Liqiang; Raffeld, Mark; Pittaluga, Stefania; Dunleavy, Kieron; Wilson, Wyndham H.; Jaffe, Elaine S.] NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Spector, Nelson; Milito, Cristiane; Morais, Jose Carlos] Univ Fed Rio de Janeiro, Dept Med Oncol, Rio De Janeiro, Brazil. [Spector, Nelson; Milito, Cristiane; Morais, Jose Carlos] Univ Fed Rio de Janeiro, Dept Pathol, Rio De Janeiro, Brazil. RP Jaffe, ES (reprint author), NCI, Pathol Lab, Ctr Canc Res, NIH, Bldg 10,Room 2B42,10 Ctr Dr, Bethesda, MD 20892 USA. EM ejaffe@mail.nih.gov OI Jaffe, Elaine/0000-0003-4632-0301 FU Center for Cancer Research, National Cancer Institute, NIH FX This work was supported by funding from the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, NIH. NR 49 TC 10 Z9 10 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD OCT PY 2010 VL 34 IS 10 BP 1425 EP 1435 DI 10.1097/PAS.0b013e3181f17d0d PG 11 WC Pathology; Surgery SC Pathology; Surgery GA 653WL UT WOS:000282128500004 PM 20871216 ER PT J AU Ellis, RD Sagara, I Durbin, A Dicko, A Shaffer, D Miller, L Assadou, MH Kone, M Kamate, B Guindo, O Fay, MP Diallo, DA Doumbo, OK Emanuel, EJ Millum, J AF Ellis, Ruth D. Sagara, Issaka Durbin, Anna Dicko, Alassane Shaffer, Donna Miller, Louis Assadou, Mahamadoun H. Kone, Mamady Kamate, Beh Guindo, Ousmane Fay, Michael P. Diallo, Dapa A. Doumbo, Ogobara K. Emanuel, Ezekiel J. Millum, Joseph TI Comparing the Understanding of Subjects Receiving a Candidate Malaria Vaccine in the United States and Mali SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID INFORMED-CONSENT; CLINICAL-TRIALS; AFRICA; COMMUNICATION; COMPREHENSION; CHILDREN; QUALITY; PHASE-1 AB Initial responses to questionnaires used to assess participants' understanding of informed consent for malaria vaccine trials conducted in the United States and Mali were tallied. Total scores were analyzed by age, sex, literacy (if known), and location. Ninety-two percent (92%) of answers by United States participants and 85% of answers by Malian participants were correct. Questions more likely to be answered incorrectly in Mali related to risk, and to the type of vaccine. For adult participants, independent predictors of higher scores were younger age and female sex in the United States, and male sex in Mali. Scores in the United States were higher than in Mali (P = 0.005). Despite this difference participants at both sites were well informed overall. Although interpretation must be qualified because questionnaires were not intended as research tools and were not standardized among sites, these results do not support concerns about systematic low understanding among research participants in developing versus developed countries. C1 [Millum, Joseph] NIH, Fogarty Int Ctr, Ctr Clin, Dept Bioeth, Bethesda, MD 20892 USA. [Ellis, Ruth D.; Miller, Louis] NIAID, MVDB, NIH, Rockville, MD USA. Univ Bamako, Fac Med Pharm & Dent, MRTC, Bamako, Mali. [Durbin, Anna; Shaffer, Donna] Johns Hopkins Ctr Immunizat Res, Washington, DC USA. [Fay, Michael P.] NIAID, Biostat Res Branch, NIH, Bethesda, MD USA. [Emanuel, Ezekiel J.] NIH, Ctr Clin, Dept Bioeth, Bethesda, MD 20892 USA. RP Millum, J (reprint author), NIH, Fogarty Int Ctr, Ctr Clin, Dept Bioeth, Bldg 10,1C118 10 Ctr Dr, Bethesda, MD 20892 USA. EM ellisru@niaid.nih.gov; isagara@icermali.org; adurbin@jhsph.edu; adicko@icermali.org; dshaffer@jhsph.edu; lmiller@niaid.nih.gov; mmaiga@icermali.org; mamady@icermali.org; bkamate@icermali.org; guindoous@icermali.org; mfay@niaid.nih.gov; dadiallo@icermali.org; okd@icermali.org; EEmanuel@cc.nih.gov; millumj@cc.nih.gov OI Fay, Michael P./0000-0002-8643-9625 FU National Institutes of Health, National Institute of Allergy and Infectious Diseases (NIAID) FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases (NIAID). NR 27 TC 8 Z9 8 U1 0 U2 1 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD OCT PY 2010 VL 83 IS 4 BP 868 EP 872 DI 10.4269/ajtmh.2010.10-0062 PG 5 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 663DF UT WOS:000282862500027 PM 20889881 ER PT J AU Bennuru, S Maldarelli, G Kumaraswami, V Klion, AD Nutman, TB AF Bennuru, Sasisekhar Maldarelli, Grace Kumaraswami, V. Klion, Amy D. Nutman, Thomas B. TI Elevated Levels of Plasma Angiogenic Factors Are Associated with Human Lymphatic Filarial Infections SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID VASCULAR ENDOTHELIAL GROWTH; EXCRETORY-SECRETORY PRODUCTS; ADULT WUCHERERIA-BANCROFTI; BRUGIA-MALAYI; FACTOR RECEPTOR-1; DIETHYLCARBAMAZINE; EXPRESSION; VEGF; ANGIOPOIETIN-1; ALBENDAZOLE AB Lymphatic dilatation, dysfunction, and lymphangiogenesis are hallmarks of patent lymphatic filariasis, observed even in those with subclinical microfilaremia, through processes associated, in part, by vascular endothelial growth factors (VEGFs). A panel of pro-angiogenic factors was measured in the plasma of subjects from filaria-endemic regions using multiplexed immunological assays. Compared with endemic normal control subjects, those with both subclinical microfilaremia, and those with longstanding lymphedema had significantly elevated levels of VEGF-A,VEGF-C, VEGF-D, and angiopoeitins (Ang-1/Ang-2), with only levels of basic fibroblast growth factor (bFGF) and placental growth factor (PIGF) being elevated only if lymphedema was evident. Furthermore, levels of these factors 1-year post-treatment with doxycycline were similar to pretreatment levels suggesting a minimal role, if any, for Wolbachia. Our data support the concept that filarial infection per se is associated with elevated levels of most of the known pro-angiogenic factors, with only a few being associated with the serious pathologic consequences associated with Wuchereria bancrofti infection. C1 [Bennuru, Sasisekhar; Maldarelli, Grace; Klion, Amy D.; Nutman, Thomas B.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. [Kumaraswami, V.] ICMR, TB Res Ctr, Madras, Tamil Nadu, India. RP Bennuru, S (reprint author), NIAID, Parasit Dis Lab, NIH, 4 Ctr Dr,Bldg 4,Rm B1-05, Bethesda, MD 20892 USA. EM bennurus@niaid.nih.gov; grace.maldarelli@gmail.com; kumaraswami@gmail.com; aklion@niaid.nih.gov; tnutman@niaid.nih.gov OI Klion, Amy/0000-0002-4986-5326 NR 51 TC 8 Z9 8 U1 0 U2 2 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD OCT PY 2010 VL 83 IS 4 BP 884 EP 890 DI 10.4269/ajtmh.2010.10-0039 PG 7 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 663DF UT WOS:000282862500031 PM 20889885 ER PT J AU Liu, Y Tuleouva, N Ramanculov, E Revzin, A AF Liu, Ying Tuleouva, Nazgul Ramanculov, Erlan Revzin, Alexander TI Aptamer-Based Electrochemical Biosensor for Interferon Gamma Detection SO ANALYTICAL CHEMISTRY LA English DT Article ID HUMAN CYTOKINES; DNA; SENSORS; RNA; OLIGONUCLEOTIDES; QUANTITATION; APTASENSORS; MOLECULES; INFECTION; ELISPOT AB In this paper, we describe the development of an electrochemical DNA aptamer-based biosensor for detection of interferon (IFN)-gamma. A DNA hairpin containing IFN-gamma-binding aptamer was thiolated, conjugated with methylene blue (MB) redox tag, and immobilized on a gold electrode by self-assembly. Binding of IFN-gamma caused the aptamer hairpin to unfold, pushing MB redox molecules away from the electrode and decreasing electron-transfer efficiency. The change in redox current was quantified using square wave voltammetry (SWV) and was found to be highly sensitive to IFN-gamma concentration. The limit of detection for optimized biosensor was 0.06 nM with linear response extending to 10 nM. This aptasensor was specific to IFN-gamma in the presence of overabundant serum proteins. Importantly, the same aptasensor could be regenerated by disrupting aptamer IFN-gamma complex in urea buffer and reused multiple times. Unlike standard sandwich immunoassays, the aptasensor described here allowed one to detect IFN-gamma binding directly without the need for multiple washing steps and reagents. An electrochemical biosensor for simple and sensitive detection of IFN-gamma demonstrated in this paper will have future applications in immunology, cancer research, and infectious disease monitoring. C1 [Liu, Ying; Tuleouva, Nazgul; Revzin, Alexander] Univ Calif Davis, Dept Biomed Engn, Davis, CA 95616 USA. [Tuleouva, Nazgul; Ramanculov, Erlan] Natl Biotechnol Ctr, Astana, Kazakhstan. RP Revzin, A (reprint author), Univ Calif Davis, Dept Biomed Engn, 451 Hlth Sci Dr,2519, Davis, CA 95616 USA. EM arevzin@ucdavis.edu RI Liu, Ying/C-7656-2012; Ramanculov, Erlan/E-2823-2013 FU NIH [REB006519Z]; NSF FX We thank Prof. Yohei Yokobayshi in the Department of Biomedical Engineering at UC Davis for helpful discussions and comments. We also thank Dr. Eugene Kamarchik, Dr. Dianlu Jiang, and Dr. Weitao Jia for their help and advice. This work was supported financially by an NSF EFRI award and by an NIH grant (REB006519Z) awarded to A.R. NR 38 TC 116 Z9 119 U1 6 U2 120 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD OCT 1 PY 2010 VL 82 IS 19 BP 8131 EP 8136 DI 10.1021/ac101409t PG 6 WC Chemistry, Analytical SC Chemistry GA 655NT UT WOS:000282257400037 PM 20815336 ER PT J AU O'Neill, SC McBride, CM Alford, SH Kaphingst, KA AF O'Neill, Suzanne C. McBride, Colleen M. Alford, Sharon Hensley Kaphingst, Kimberly A. TI Preferences for Genetic and Behavioral Health Information: The Impact of Risk Factors and Disease Attributions SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Article DE Genetic testing; Attribution; Family history; Behavioral risk factors ID COLORECTAL-CANCER; PERCEIVED RISK; PHYSICAL-ACTIVITY; SELF-REGULATION; PUBLIC-HEALTH; SEEKING; HERITABILITY; ENVIRONMENT; PERCEPTIONS; NUTRITION AB Increased availability of genetic risk information may lead the public to give precedence to genetic causation over behavioral/environmental factors, decreasing motivation for behavior change. Few population-based data inform these concerns. We assess the association of family history, behavioral risks, and causal attributions for diseases and the perceived value of pursuing information emphasizing health habits or genes. 1,959 healthy adults completed a survey that assessed behavioral risk factors, family history, causal attributions of eight diseases, and health information preferences. Participants' causal beliefs favored health behaviors over genetics. Interest in behavioral information was higher than in genetic information. As behavioral risk factors increased, inclination toward genetic explanations increased; interest in how health habits affect disease risk decreased. Those at greatest need for behavior change may hold attributions that diminish interest in information for behavior change. Enhancing understanding of gene-environment influences could be explored to increase engagement with health information. C1 [O'Neill, Suzanne C.; McBride, Colleen M.; Kaphingst, Kimberly A.] NHGRI, NIH, Social & Behav Res Branch, Bethesda, MD 20892 USA. [Alford, Sharon Hensley] Henry Ford Hlth Syst, Detroit, MI USA. RP O'Neill, SC (reprint author), Georgetown Univ, Lombardi Comprehens Canc Ctr, Canc Control Program, 3300 Whitehaven St,Suite 4100, Washington, DC 20007 USA. EM sco4@georgetown.edu FU Intramural NIH HHS; NCI NIH HHS [U19 CA 079689, P30 CA051008, U19 CA079689]; NHGRI NIH HHS [HHSN268200782096C] NR 59 TC 23 Z9 23 U1 1 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD OCT PY 2010 VL 40 IS 2 BP 127 EP 137 DI 10.1007/s12160-010-9197-1 PG 11 WC Psychology, Multidisciplinary SC Psychology GA 648SA UT WOS:000281713100001 PM 20532842 ER PT J AU Magnani, JW Johnson, VM Sullivan, LM Lubitz, SA Schnabel, RB Ellinor, PT Benjamin, EJ AF Magnani, Jared W. Johnson, Victor M. Sullivan, Lisa M. Lubitz, Steven A. Schnabel, Renate B. Ellinor, Patrick T. Benjamin, Emelia J. TI P-Wave Indices: Derivation of Reference Values from the Framingham Heart Study SO ANNALS OF NONINVASIVE ELECTROCARDIOLOGY LA English DT Article DE electrocardiogram; P waves; epidemiology; reference values ID GENERAL-HOSPITAL POPULATION; ATRIAL-FIBRILLATION; INTERATRIAL BLOCK; RISK PROFILE; DISPERSION; INTERVAL; ELECTROCARDIOGRAM; HYPERTENSION; PREVALENCE; FAILURE AB Methods: We randomly selected 20 men and 20 women from 10-year age intervals between < 25 years to 76-85 years from the Framingham Heart Study Original and Offspring Cohorts, excluding subjects with prevalent cardiovascular disease, hypertension, diabetes or obesity. The total included 295 subjects; eligibility in women > 75 years was limited by exclusion criteria. We used a digital measurement technique with demonstrated intrarater reproducibility to determine P-wave indices. P-wave indices examined included the maximum, mean, lead II and PR durations, dispersion, and the standard deviation of duration. Results: All P-wave indices were significantly (P < 0.0001) correlated with advancing age. Means of all P-wave indices were lower in women as compared to men. PR-interval duration was strongly correlated with maximum, mean, and lead II mean P-wave durations. In multivariable models adjusting for significant anthropometric and clinical associations risk factors, significant differences persisted by age and sex in P-wave indices. Conclusions. In our healthy sample without cardiovascular disease, hypertension, diabetes, or obesity, men and older subjects had longer mean P-wave indices. Our description of P-wave indices establishes reference values for future comparative studies and facilitates the classification of P-wave indices. Ann Noninvasive Electrocardiol 2010;15(4):344-352. C1 [Magnani, Jared W.; Benjamin, Emelia J.] Boston Univ, Sch Med, Sect Cardiovasc Med, Boston, MA 02118 USA. [Magnani, Jared W.; Benjamin, Emelia J.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Johnson, Victor M.; Sullivan, Lisa M.] Boston Univ, Sch Publ Hlth, Dept Stat, Boston, MA USA. [Lubitz, Steven A.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Lubitz, Steven A.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Schnabel, Renate B.] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Mainz, Germany. [Benjamin, Emelia J.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA. [Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. RP Benjamin, EJ (reprint author), Boston Univ, Sch Med & Publ Hlth, Framingham Heart Study, 73 Mt Wayte Ave, Framingham, MA 01702 USA. EM emelia@bu.edu RI Schnabel, Renate/F-6527-2014; OI Sullivan, Lisa/0000-0003-0726-7149; Benjamin, Emelia/0000-0003-4076-2336 FU American Heart Association [09FTF2190028, RC1 HL101056, HL092577] FX Funding: This research was funded by American Heart Association Award 09FTF2190028; RC1 HL101056; HL092577. NR 29 TC 15 Z9 15 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1082-720X J9 ANN NONINVAS ELECTRO JI Ann. Noninvasive Electrocardiol. PD OCT PY 2010 VL 15 IS 4 BP 344 EP 352 DI 10.1111/j.1542-474X.2010.00390.x PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 666BG UT WOS:000283082200008 PM 20946557 ER PT J AU Stewart, PA Coble, JB Vermeulen, R Schleiff, P Blair, A Lubin, J Attfield, M Silverman, DT AF Stewart, Patricia A. Coble, Joseph B. Vermeulen, Roel Schleiff, Patricia Blair, Aaron Lubin, Jay Attfield, Michael Silverman, Debra T. TI The Diesel Exhaust in Miners Study: I. Overview of the Exposure Assessment Process SO ANNALS OF OCCUPATIONAL HYGIENE LA English DT Article DE diesel exhaust; elemental carbon; exposure assessment; miners ID OCCUPATIONAL-EXPOSURE; ELEMENTAL CARBON; RETROSPECTIVE EXPOSURE; TRUCKING INDUSTRY; WORKERS; PARTICLES; HEAVY; DUST AB This report provides an overview of the exposure assessment process for an epidemiologic study that investigated mortality, with a special focus on lung cancer, associated with diesel exhaust (DE) exposure among miners. Details of several components are provided in four other reports. A major challenge for this study was the development of quantitative estimates of historical exposures to DE. There is no single standard method for assessing the totality of DE, so respirable elemental carbon (REC), a component of DE, was selected as the primary surrogate in this study. Air monitoring surveys at seven of the eight study mining facilities were conducted between 1998 and 2001 and provided reference personal REC exposure levels and measurements for other agents and DE components in the mining environment. (The eighth facility had closed permanently prior to the surveys.) Exposure estimates were developed for mining facility/department/job/year combinations. A hierarchical grouping strategy was developed for assigning exposure levels to underground jobs [based on job titles, on the amount of time spent in various areas of the underground mine, and on similar carbon monoxide (CO, another DE component) concentrations] and to surface jobs (based on the use of, or proximity to, diesel-powered equipment). Time trends in air concentrations for underground jobs were estimated from mining facility-specific prediction models using diesel equipment horsepower, total air flow rates exhausted from the underground mines, and, because there were no historical REC measurements, historical measurements of CO. Exposures to potentially confounding agents, i.e. respirable dust, silica, radon, asbestos, and non-diesel sources of polycyclic aromatic hydrocarbons, also were assessed. Accuracy and reliability of the estimated REC exposures levels were evaluated by comparison with several smaller datasets and by development of alternative time trend models. During 1998-2001, the average measured REC exposure level by facility ranged from 40 to 384 mu g m(-3) for the underground workers and from 2 to 6 mu g m(-3) for the surface workers. For one prevalent underground job, 'miner operator', the maximum annual REC exposure estimate by facility ranged up to 685% greater than the corresponding 1998-2001 value. A comparison of the historical CO estimates from the time trend models with 1976-1977 CO measurements not used in the modeling found an overall median relative difference of 29%. Other comparisons showed similar levels of agreement. The assessment process indicated large differences in REC exposure levels over time and across the underground operations. Method evaluations indicated that the final estimates were consistent with those from alternative time trend models and demonstrated moderate to high agreement with external data. C1 [Stewart, Patricia A.; Coble, Joseph B.; Vermeulen, Roel; Blair, Aaron; Lubin, Jay; Silverman, Debra T.] US Natl Canc Inst, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Schleiff, Patricia; Attfield, Michael] US Natl Inst Occupat Safety & Hlth, Surveillance Branch, Div Resp Dis Studies, Morgantown, WV 26505 USA. RP Silverman, DT (reprint author), US Natl Canc Inst, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. EM silvermd@mail.nih.gov RI Vermeulen, Roel/F-8037-2011 OI Vermeulen, Roel/0000-0003-4082-8163 FU National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics; National Institute for Occupational Safety and Health, Division of Respiratory Disease Studies FX Intramural Research Program of the National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics, and the National Institute for Occupational Safety and Health, Division of Respiratory Disease Studies. NR 33 TC 36 Z9 36 U1 2 U2 15 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0003-4878 J9 ANN OCCUP HYG JI Ann. Occup. Hyg. PD OCT PY 2010 VL 54 IS 7 BP 728 EP 746 DI 10.1093/annhyg/meq022 PG 19 WC Public, Environmental & Occupational Health; Toxicology SC Public, Environmental & Occupational Health; Toxicology GA 666DY UT WOS:000283093500002 PM 20876233 ER PT J AU Coble, JB Stewart, PA Vermeulen, R Yereb, D Stanevich, R Blair, A Silverman, DT Attfield, M AF Coble, Joseph B. Stewart, Patricia A. Vermeulen, Roel Yereb, Daniel Stanevich, Rebecca Blair, Aaron Silverman, Debra T. Attfield, Michael TI The Diesel Exhaust in Miners Study: II. Exposure Monitoring Surveys and Development of Exposure Groups SO ANNALS OF OCCUPATIONAL HYGIENE LA English DT Article DE diesel exhaust; miners; elemental carbon; exposure assessment; job groups ID ELEMENTAL CARBON; PARTICULATE MATTER AB Air monitoring surveys were conducted between 1998 and 2001 at seven non-metal mining facilities to assess exposure to respirable elemental carbon (REC), a component of diesel exhaust (DE), for an epidemiologic study of miners exposed to DE. Personal exposure measurements were taken on workers in a cross-section of jobs located underground and on the surface. Air samples taken to measure REC were also analyzed for respirable organic carbon (ROC). Concurrent measurements to assess exposure to nitric oxide (NO) and nitrogen dioxide (NO(2)), two gaseous components of DE, were also taken. The REC measurements were used to develop quantitative estimates of average exposure levels by facility, department, and job title for the epidemiologic analysis. Each underground job was assigned to one of three sets of exposure groups from specific to general: (i) standardized job titles, (ii) groups of standardized job titles combined based on the percentage of time in the major underground areas, and (iii) larger groups based on similar area carbon monoxide (CO) air concentrations. Surface jobs were categorized based on their use of diesel equipment and proximity to DE. A total of 779 full-shift personal measurements were taken underground. The average REC exposure levels for underground jobs with five or more measurements ranged from 31 to 58 mu g m(-3) at the facility with the lowest average exposure levels and from 313 to 488 mu g m(-3) at the facility with the highest average exposure levels. The average REC exposure levels for surface workers ranged from 2 to 6 mu g m(-3) across the seven facilities. There was much less contrast in the ROC compared with REC exposure levels measured between surface and underground workers within each facility, as well as across the facilities. The average ROC levels underground ranged from 64 to 195 mu g m(-3), while on the surface, the average ROC levels ranged from 38 to 71 mu g m(-3) by facility, an similar to 2- to 3-fold difference. The average NO and NO(2) levels underground ranged from 0.20 to 1.49 parts per million (ppm) and from 0.10 to 0.60 ppm, respectively, and were similar to 10 times higher than levels on the surface, which ranged from 0.02 to 0.11 ppm and from 0.01 to 0.06 ppm, respectively. The ROC, NO, and NO(2) concentrations underground were correlated with the REC levels (r = 0.62, 0.71, and 0.62, respectively). A total of 80% of the underground jobs were assigned an exposure estimate based on measurements taken for the specific job title or for other jobs with a similar percentage of time spent in the major underground work areas. The average REC exposure levels by facility were from 15 to 64 times higher underground than on the surface. The large contrast in exposure levels measured underground versus on the surface, along with the differences between the mining facilities and between underground jobs within the facilities resulted in a wide distribution in the exposure estimates for evaluation of exposure-response relationships in the epidemiologic analyses. C1 [Yereb, Daniel; Stanevich, Rebecca; Attfield, Michael] US Natl Inst Occupat Safety & Hlth, Surveillance Branch, Div Resp Dis Studies, Morgantown, WV 26505 USA. [Coble, Joseph B.; Stewart, Patricia A.; Vermeulen, Roel; Blair, Aaron; Silverman, Debra T.] US Natl Canc Inst, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Attfield, M (reprint author), US Natl Inst Occupat Safety & Hlth, Surveillance Branch, Div Resp Dis Studies, Morgantown, WV 26505 USA. EM mda1@cdc.gov RI Vermeulen, Roel/F-8037-2011 OI Vermeulen, Roel/0000-0003-4082-8163 FU National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics; National Institute for Occupational Safety and Health, Division of Respiratory Disease Studies FX Intramural Research Program of the National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics, and the National Institute for Occupational Safety and Health, Division of Respiratory Disease Studies. NR 21 TC 27 Z9 27 U1 1 U2 21 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0003-4878 J9 ANN OCCUP HYG JI Ann. Occup. Hyg. PD OCT PY 2010 VL 54 IS 7 BP 747 EP 761 DI 10.1093/annhyg/meq024 PG 15 WC Public, Environmental & Occupational Health; Toxicology SC Public, Environmental & Occupational Health; Toxicology GA 666DY UT WOS:000283093500003 PM 20876232 ER PT J AU Vermeulen, R Coble, JB Yereb, D Lubin, JH Blair, A Portengen, L Stewart, PA Attfield, M Silverman, DT AF Vermeulen, Roel Coble, Joseph B. Yereb, Daniel Lubin, Jay H. Blair, Aaron Portengen, Lutzen Stewart, Patricia A. Attfield, Michael Silverman, Debra T. TI The Diesel Exhaust in Miners Study: III. Interrelations between Respirable Elemental Carbon and Gaseous and Particulate Components of Diesel Exhaust derived from Area Sampling in Underground Non-metal Mining Facilities SO ANNALS OF OCCUPATIONAL HYGIENE LA English DT Article DE carbon dioxide; carbon monoxide; diesel exhaust; elemental carbon; miners; nitric oxide; nitrogen dioxide; particulates ID OCCUPATIONAL-EXPOSURE; MATTER AB Diesel exhaust (DE) has been implicated as a potential lung carcinogen. However, the exact components of DE that might be involved have not been clearly identified. In the past, nitrogen oxides (NO(x)) and carbon oxides (CO(x)) were measured most frequently to estimate DE, but since the 1990s, the most commonly accepted surrogate for DE has been elemental carbon (EC). We developed quantitative estimates of historical exposure levels of respirable elemental carbon (REC) for an epidemiologic study of mortality, particularly lung cancer, among diesel-exposed miners by back-extrapolating 1998-2001 REC exposure levels using historical measurements of carbon monoxide (CO). The choice of CO was based on the availability of historical measurement data. Here, we evaluated the relationship of REC with CO and other current and historical components of DE from side-by-side area measurements taken in underground operations of seven non-metal mining facilities. The Pearson correlation coefficient of the natural log-transformed (Ln)REC measurements with the Ln(CO) measurements was 0.4. The correlation of REC with the other gaseous, organic carbon (OC), and particulate measurements ranged from 0.3 to 0.8. Factor analyses indicated that the gaseous components, including CO, together with REC, loaded most strongly on a presumed 'Diesel exhaust' factor, while the OC and particulate agents loaded predominantly on other factors. In addition, the relationship between Ln(REC) and Ln(CO) was approximately linear over a wide range of REC concentrations. The fact that CO correlated with REC, loaded on the same factor, and increased linearly in log-log space supported the use of CO in estimating historical exposure levels to DE. C1 [Vermeulen, Roel; Coble, Joseph B.; Lubin, Jay H.; Blair, Aaron; Stewart, Patricia A.; Silverman, Debra T.] US Natl Canc Inst, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Yereb, Daniel; Attfield, Michael] US Natl Inst Occupat Safety & Hlth, Surveillance Branch, Div Resp Dis Studies, Morgantown, WV 26505 USA. [Vermeulen, Roel; Portengen, Lutzen] Univ Utrecht, Inst Risk Assessment Sci, Utrecht, Netherlands. RP Silverman, DT (reprint author), US Natl Canc Inst, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. EM silvermd@mail.nih.gov RI Vermeulen, Roel/F-8037-2011 OI Vermeulen, Roel/0000-0003-4082-8163 FU National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics; National Institute for Occupational Safety and Health, Division of Respiratory Disease Studies FX Intramural Research Program of the National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics, and the National Institute for Occupational Safety and Health, Division of Respiratory Disease Studies. NR 22 TC 24 Z9 24 U1 0 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0003-4878 J9 ANN OCCUP HYG JI Ann. Occup. Hyg. PD OCT PY 2010 VL 54 IS 7 BP 762 EP 773 DI 10.1093/annhyg/meq023 PG 12 WC Public, Environmental & Occupational Health; Toxicology SC Public, Environmental & Occupational Health; Toxicology GA 666DY UT WOS:000283093500004 PM 20876234 ER PT J AU Vermeulen, R Coble, JB Lubin, JH Portengen, L Blair, A Attfield, MD Silverman, DT Stewart, PA AF Vermeulen, Roel Coble, Joseph B. Lubin, Jay H. Portengen, Lutzen Blair, Aaron Attfield, Michael D. Silverman, Debra T. Stewart, Patricia A. TI The Diesel Exhaust in Miners Study: IV. Estimating Historical Exposures to Diesel Exhaust in Underground Non-metal Mining Facilities SO ANNALS OF OCCUPATIONAL HYGIENE LA English DT Article DE elemental carbon; miners; exposure assessment; carbon monoxide; diesel exhaust ID PARTICULATE MATTER; RETROSPECTIVE EXPOSURE; ELEMENTAL CARBON; DUST; VALIDATION AB We developed quantitative estimates of historical exposures to respirable elemental carbon (REC) for an epidemiologic study of mortality, including lung cancer, among diesel-exposed miners at eight non-metal mining facilities [the Diesel Exhaust in Miners Study (DEMS)]. Because there were no historical measurements of diesel exhaust (DE), historical REC (a component of DE) levels were estimated based on REC data from monitoring surveys conducted in 1998-2001 as part of the DEMS investigation. These values were adjusted for underground workers by carbon monoxide (CO) concentration trends in the mines derived from models of historical CO (another DE component) measurements and DE determinants such as engine horsepower (HP; 1 HP = 0.746 kW) and mine ventilation. CO was chosen to estimate historical changes because it was the most frequently measured DE component in our study facilities and it was found to correlate with REC exposure. Databases were constructed by facility and year with air sampling data and with information on the total rate of airflow exhausted from the underground operations in cubic feet per minute (CFM) (1 CFM = 0.0283 m(3) min(-1)), HP of the diesel equipment in use (ADJ HP), and other possible determinants. The ADJ HP purchased after 1990 (ADJ HP(1990+)) was also included to account for lower emissions from newer, cleaner engines. Facility-specific CO levels, relative to those in the DEMS survey year for each year back to the start of dieselization (1947-1967 depending on facility), were predicted based on models of observed CO concentrations and log-transformed (Ln) ADJ HP/CFM and Ln(ADJ HP(1990+)). The resulting temporal trends in relative CO levels were then multiplied by facility/department/job-specific REC estimates derived from the DEMS surveys personal measurements to obtain historical facility/department/job/year-specific REC exposure estimates. The facility-specific temporal trends of CO levels (and thus the REC estimates) generated from these models indicated that CO concentrations had been generally greater in the past than during the 1998-2001 DEMS surveys, with the highest levels ranging from 100 to 685% greater (median: 300%). These levels generally occurred between 1970 and the early 1980s. A comparison of the CO facility-specific model predictions with CO air concentration measurements from a 1976-1977 survey external to the modeling showed that our model predictions were slightly lower than those observed (median relative difference of 29%; range across facilities: 49 to -25%). In summary, we successfully modeled past CO concentration levels using selected determinants of DE exposure to derive retrospective estimates of REC exposure. The results suggested large variations in REC exposure levels both between and within the underground operations of the facilities and over time. These REC exposure estimates were in a plausible range and were used in the investigation of exposure-response relationships in epidemiologic analyses. C1 [Vermeulen, Roel; Coble, Joseph B.; Lubin, Jay H.; Blair, Aaron; Silverman, Debra T.; Stewart, Patricia A.] US Natl Canc Inst, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Portengen, Lutzen] Univ Utrecht, Inst Risk Assessment Sci, NL-3584 CK Utrecht, Netherlands. [Attfield, Michael D.] US Natl Inst Occupat Safety & Hlth, Surveillance Branch, Div Resp Dis Studies, Morgantown, WV 26505 USA. RP Silverman, DT (reprint author), US Natl Canc Inst, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. EM silvermd@mail.nih.gov RI Vermeulen, Roel/F-8037-2011 OI Vermeulen, Roel/0000-0003-4082-8163 FU National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics; National Institute for Occupational Safety and Health, Division of Respiratory Disease Studies FX Intramural Research Program of the National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics, and the National Institute for Occupational Safety and Health, Division of Respiratory Disease Studies. NR 32 TC 36 Z9 36 U1 2 U2 16 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0003-4878 J9 ANN OCCUP HYG JI Ann. Occup. Hyg. PD OCT PY 2010 VL 54 IS 7 BP 774 EP 788 DI 10.1093/annhyg/meq025 PG 15 WC Public, Environmental & Occupational Health; Toxicology SC Public, Environmental & Occupational Health; Toxicology GA 666DY UT WOS:000283093500005 PM 20876235 ER PT J AU Kerr, D O'Connell, MJ Lavery, IC Gray, R Yothers, G Quirke, P Lopatin, M Clark-Langone, K Lee, M Wolmark, N AF Kerr, D. O'Connell, M. J. Lavery, I. C. Gray, R. Yothers, G. Quirke, P. Lopatin, M. Clark-Langone, K. Lee, M. Wolmark, N. TI CONSIDERATIONS IN THE DEVELOPMENT AND VALIDATION OF GENOMIC TESTS FOR CANCER RECURRENCE AND TREATMENT BENEFIT SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 35th European-Society-for-Medical-Oncology (ESMO) Congress CY OCT 08-12, 2010 CL Milan, ITALY SP European Soc Med Oncol C1 [Kerr, D.] Univ Oxford, Dept Clin Pharmacol, Oxford, England. [O'Connell, M. J.; Yothers, G.; Wolmark, N.] Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA. [Lavery, I. C.] Cleveland Clin, Cleveland, OH 44106 USA. [Gray, R.] Univ Birmingham, Birmingham, W Midlands, England. [Quirke, P.] Leeds Inst Mol Med, Leeds, W Yorkshire, England. [Lee, M.] Genom Hlth Inc, Oncol Dev, Redwood City, CA USA. 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 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD OCT PY 2010 VL 21 SU 8 BP 44 EP 44 PG 1 WC Oncology SC Oncology GA 666LE UT WOS:000283115900102 ER PT J AU Crea, F Fornaro, L Paolicchi, E Masi, G Loupakis, F Salvatore, L Farrar, WL Falcone, A Danesi, R AF Crea, F. Fornaro, L. Paolicchi, E. Masi, G. Loupakis, F. Salvatore, L. Farrar, W. L. Falcone, A. Danesi, R. TI AN EZH2 POLYMORPHISM PREDICTS PROGRESSION-FREE SURVIVAL (PFS) IN METASTATIC COLORECTAL CANCER (CRC) PATIENTS TREATED WITH FIRST-LINE FOLFIRI PLUS BEVACIZUMAB (BV) SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 35th European-Society-for-Medical-Oncology (ESMO) Congress CY OCT 08-12, 2010 CL Milan, ITALY SP European Soc Med Oncol C1 [Crea, F.; Paolicchi, E.; Danesi, R.] Univ Pisa, Div Pharmacol, Pisa, Italy. [Fornaro, L.; Masi, G.; Loupakis, F.; Salvatore, L.] Azienda Osped Univ Pisana, Uo Oncol Med Univ 2, Pisa, Italy. [Farrar, W. L.] NCI, Canc Stem Cell Sect, Lab Canc Prevent, Frederick, MD 21701 USA. RI Crea, Francesco /I-8383-2015 NR 0 TC 0 Z9 0 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD OCT PY 2010 VL 21 SU 8 BP 65 EP 65 PG 1 WC Oncology SC Oncology GA 666LE UT WOS:000283115900183 ER PT J AU Cappuzzo, F Ciuleanu, T Park, K Wu, Y Giaccone, G AF Cappuzzo, F. Ciuleanu, T. Park, K. Wu, Y. Giaccone, G. TI ERLOTINIB MAINTENANCE THERAPY IN PATIENTS WITH STABLE DISEASE AFTER FIRST-LINE PLATINUM-DOUBLET CHEMOTHERAPY FOR ADVANCED NSCLC SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 35th European-Society-for-Medical-Oncology (ESMO) Congress CY OCT 08-12, 2010 CL Milan, ITALY SP European Soc Med Oncol C1 [Cappuzzo, F.] Osped Civile, Livorno, Italy. [Ciuleanu, T.] Oncol Inst Ion Chircuta, Cluj Napoca, Romania. [Park, K.] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Div Hem Onc,Dept Med, Seoul, South Korea. [Wu, Y.] Guangdong Gen Hosp, Guangdong Lung Canc Inst, Guangzhou, Guangdong, Peoples R China. [Giaccone, G.] NCI, Chief Med Oncol Branch, CCR, NIH, Bethesda, MD 20892 USA. RI Ciuleanu, Tudor Eliade/C-3996-2011 NR 0 TC 2 Z9 2 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD OCT PY 2010 VL 21 SU 8 BP 124 EP 124 PG 1 WC Oncology SC Oncology GA 666LE UT WOS:000283115900384 ER PT J AU Lee, JM Kohn, EC AF Lee, J. -M. Kohn, E. C. TI Proteomics as a guiding tool for more effective personalized therapy SO ANNALS OF ONCOLOGY LA English DT Article DE Ovarian cancer; proteomics; therapy ID PHASE PROTEIN MICROARRAYS; OVARIAN-CANCER; LUNG-CANCER; COLORECTAL-CANCER; MASS-SPECTROMETRY; BIOMARKER; VALIDATION; CARCINOMAS; MUTATIONS; GEFITINIB AB Ovarian cancer remains the deadliest gynecological malignancy in the Western world and is most often diagnosed at a rarely curable late stage. Examination of protein end points has been employed as an investigative mechanism to guide targeted therapy and to stratify ovarian cancer. Proteomics allows characterization of the proteins and the associated protein and peptide modifications. This has given us insight into the perturbations of signaling pathways within tumor cells and has improved the discovery of new drug targets and possible prognostic indicators of outcome and disease response to therapy. Development of validated assays that survey the genetic and/or proteomic make-up of an individual tumor will add greatly to the histological classification of the tumor and may lead to different treatment approaches tailored to the unique expression pattern of each individual patient. It is anticipated that application of proteomics may bring to reality the clinical adoption of molecular stratification, e.g. not, 'is the gene overexpressed?', but 'is the pathway upregulated?' This will be successful if validated peptide biomarkers are applied for patient selection prospectively and with inclusion of preplanned biological correlates. These events will guide future directions of proteomics as a selector and as a validator and will guide how we integrate proteomics information daily into patient care and into selecting therapy of advanced and recurrent ovarian cancer and other cancers. C1 [Lee, J. -M.; Kohn, E. C.] NCI, Mol Signaling Sect, Med Oncol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Lee, JM (reprint author), 10 Ctr Dr MSC1906,Bldg 10,Room 12N-226, Bethesda, MD 20892 USA. EM leej6@mail.nih.gov FU Center for Cancer Research, National Cancer Institute, USA FX This work was supported by the Intramural Program of the Center for Cancer Research, National Cancer Institute, USA. NR 26 TC 18 Z9 18 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD OCT PY 2010 VL 21 SU 7 BP 205 EP 210 DI 10.1093/annonc/mdq375 PG 6 WC Oncology SC Oncology GA 666FK UT WOS:000283099200001 ER PT J AU Wells, SA Robinson, BG Gagel, RF Dralle, H Fagin, JA Santoro, M Baudin, E Vasselli, J Read, J Schlumberger, M AF Wells, S. A. Robinson, B. G. Gagel, R. F. Dralle, H. Fagin, J. A. Santoro, M. Baudin, E. Vasselli, J. Read, J. Schlumberger, M. TI VANDETANIB IN LOCALLY ADVANCED OR METASTATIC MEDULLARY THYROID CANCER (MTC): A RANDOMIZED, DOUBLE-BLIND PHASE III TRIAL (ZETA) SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 35th European-Society-for-Medical-Oncology (ESMO) Congress CY OCT 08-12, 2010 CL Milan, ITALY SP European Soc Med Oncol C1 [Wells, S. A.] Natl Canc Inst, Thyroid Oncol Clin, Bethesda, MD USA. [Robinson, B. G.] Univ Sydney, Kolling Inst Med Res, Sydney, NSW 2006, Australia. [Gagel, R. F.] UTMD Anderson Canc Ctr, Houston, TX USA. [Dralle, H.] Univ Halle Wittenberg, Halle, Germany. [Fagin, J. A.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Santoro, M.] Univ Naples Federico II, Dipartimento Biol & Patol Cellulare & Mol, Naples, Italy. [Baudin, E.; Schlumberger, M.] Inst Gustave Roussy, Villejuif, France. [Vasselli, J.] AstraZeneca, Clin Res Oncol, Wilmington, DE USA. [Read, J.] AstraZeneca, Biostat, Macclesfield, Cheshire, England. NR 0 TC 1 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD OCT PY 2010 VL 21 SU 8 BP 315 EP 315 PG 1 WC Oncology SC Oncology GA 684YX UT WOS:000284592300208 ER PT J AU Chuang, E Wiener, N Christos, P Kessler, R Cobham, M Donovan, D Goldberg, GL Caputo, T Doyle, A Vahdat, L Sparano, JA AF Chuang, E. Wiener, N. Christos, P. Kessler, R. Cobham, M. Donovan, D. Goldberg, G. L. Caputo, T. Doyle, A. Vahdat, L. Sparano, J. A. TI Phase I trial of ixabepilone plus pegylated liposomal doxorubicin in patients with adenocarcinoma of breast or ovary dagger double dagger SO ANNALS OF ONCOLOGY LA English DT Article DE breast cancer; ixabepilone; liposomal doxorubicin; ovarian cancer ID EPOTHILONE-B ANALOG; MICROTUBULE-STABILIZING AGENTS; CLINICAL-TRIAL; SOLID TUMORS; III TRIAL; CANCER; BMS-247550; ANTHRACYCLINE; PHARMACOKINETICS; CARDIOTOXICITY AB Methods: Patients with recurrent ovarian or breast carcinoma received PLD every 3 or 4 weeks plus five different dose schemas of ixabepilone in cohorts of three to six patients. Results: Thirty patients received a total of 142 treatment cycles of the PLD-ixabepilone combination. The recommended phase II dose and schedule of ixabepilone was 16 mg/m(2) on days 1, 8, and 15 plus PLD 30 mg/m(2) given on day 1, repeated every 4 weeks. Hand-foot syndrome and mucositis were dose limiting when both ixabepilone and PLD were given every 3 or 4 weeks. Objective responses were observed in 3 of 13 patients (23%) with breast cancer and 5 of 17 patients (29%) with ovarian cancer. Conclusion: Ixabepilone may be safely combined with PLD, but tolerability is highly dependent upon the scheduling of both agents. This combination demonstrated efficacy in patients with breast and ovarian cancer and merits further evaluation in these settings. C1 [Chuang, E.; Wiener, N.; Kessler, R.; Cobham, M.; Donovan, D.; Vahdat, L.] Weill Cornell Med Coll, Dept Med, New York, NY 10065 USA. [Christos, P.] Weill Cornell Med Coll, Div Biostat & Epidemiol, Dept Publ Hlth, New York, NY 10065 USA. [Goldberg, G. L.] Albert Einstein Coll Med, Dept Obstet & Gynecol, Montefiore Med Ctr, Bronx, NY 10467 USA. [Caputo, T.] Weill Cornell Med Coll, Dept Obstet & Gynecol, New York, NY USA. [Doyle, A.] Natl Canc Inst, Canc Therapy Evaluat Program, Bethesda, MD USA. [Sparano, J. A.] Albert Einstein Coll Med, Dept Med & Gynecol, Montefiore Med Ctr, Bronx, NY 10467 USA. RP Chuang, E (reprint author), Weill Cornell Med Coll, Dept Med, 425 E 61st St, New York, NY 10065 USA. EM elc2007@med.cornell.edu FU Bristol Myers Squibb FX LV has received research funding and has served on advisory boards for Bristol Myers Squibb. JAS has served as a consultant for Bristol Myers Squibb and for Johnson and Johnson and has received honoraria from Bristol Myers Squibb. The other authors have no conflicts of interests. NR 27 TC 4 Z9 4 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD OCT PY 2010 VL 21 IS 10 BP 2075 EP 2080 DI 10.1093/annonc/mdq080 PG 6 WC Oncology SC Oncology GA 654LA UT WOS:000282168600021 PM 20357034 ER PT J AU Hopping, SB Janjanin, S Tanna, N Joshi, AS AF Hopping, Steven B. Janjanin, Sasa Tanna, Neil Joshi, Arjun S. TI The S-Plus lift: a short-scar, long-flap rhytidectomy SO ANNALS OF THE ROYAL COLLEGE OF SURGEONS OF ENGLAND LA English DT Article DE Rhytidectomy; Face-lift; SMAS; SMASeetomy; Purse-string suture; Imbrication ID SMAS; SMASECTOMY; FACELIFT; MIDFACE; SUTURE AB INTRODUCTION As rhytidectomy is one of the most elective surgical procedures, there is a strong trend toward less aggressive operative techniques. The authors introduce the S-Plus lift, a 'long flap' superficial musculo-aponeurotic system (SMAS) imbrication technique that diminishes risks, decreases recovery time, and yields long-lasting results. PATIENTS AND METHODS This paper describes a novel approach to mid-facial rejuvenation that combines the limited incision of an S-lift with two SMASectomies, purse-string suture imbrication of the extended supraplatysmal plane (ESP) and SMAS, and malar soft tissue suspension. SMAS excisions are performed pre-auricularly, and in the region overlying the anterior edge of the parotid gland. Purse-string imbrication sutures are designed to close the SMAS defects, pull the soft tissues of the neck upward, pull the jowl and lower face posteriorly and superiorly, and tighten the platysma. Ancillary purse-string suture lifts the malar fat pad and cheek soft tissues vertically, which achieves mid-face fullness and lifting. Compared to S-lift, the technique extends its efficacy in those patients who have moderate-to-severe mid-facial laxity, prominent nasolabial folds, and platysma redundancy. RESULTS A review of 144 consecutive S-Plus lifts performed by a single surgeon (SBH), with at least 6 months of follow-up, was performed. Over a 3-year period, 130 (90.3%) females and 14 (9.7%) males underwent S-Plus lift. S-Plus lift as primary rhytidectomy was performed in 132 (91.7%) and as secondary in 12 (8.3%) cases. Complication rate was low and comparable with other techniques of rhytidectomy. CONCLUSIONS The S-Plus lift is a novel, hybrid technique with pleasing results, short down-time, and high patient satisfaction rate. The technique combines two SMASectomies with purse-string suture imbrication of the ESP and SMAS, and malar fat suture suspension. C1 [Janjanin, Sasa] Zagreb Clin Hosp Ctr, Univ Dept Otorhinolaryngol Head & Neck Surg, HR-10000 Zagreb, Croatia. [Hopping, Steven B.; Tanna, Neil; Joshi, Arjun S.] George Washington Univ, Div Otolaryngol Head & Neck Surg, Washington, DC USA. [Hopping, Steven B.] Ctr Cosmet Surg, Washington, DC USA. [Hopping, Steven B.] Washington Hair Inst, Washington, DC USA. [Janjanin, Sasa] NIAMSD, NIH, Bethesda, MD 20892 USA. RP Janjanin, S (reprint author), Zagreb Clin Hosp Ctr, Univ Dept Otorhinolaryngol Head & Neck Surg, Kispaticeva 12, HR-10000 Zagreb, Croatia. EM s_janjanin@yahoo.com NR 19 TC 3 Z9 4 U1 0 U2 1 PU ROYAL COLL SURGEONS ENGLAND PI LONDON PA 35-43 LINCOLN'S INN FIELDS, LONDON WC2A 3PN, ENGLAND SN 0035-8843 J9 ANN ROY COLL SURG JI Ann. R. Coll. Surg. Engl. PD OCT PY 2010 VL 92 IS 7 BP 577 EP 582 DI 10.1308/003588410X12699663904439 PG 6 WC Surgery SC Surgery GA 662JW UT WOS:000282804600009 PM 20594404 ER PT J AU Robey, RW Massey, PR Amiri-Kordestani, L Bates, SE AF Robey, Robert W. Massey, Paul R. Amiri-Kordestani, Laleh Bates, Susan E. TI ABC Transporters: Unvalidated Therapeutic Targets in Cancer and the CNS SO ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY LA English DT Article DE ABC transporters; drug resistance; P-glycoprotein ID ACUTE-MYELOID-LEUKEMIA; CELL LUNG-CANCER; BINDING CASSETTE TRANSPORTERS; BLOOD-BRAIN-BARRIER; IMATINIB MESYLATE GLEEVEC; HEREDITARY BREAST-CANCER; P-GLYCOPROTEIN; RESISTANCE PROTEIN; MULTIDRUG-RESISTANCE; DRUG-RESISTANCE AB The discovery of the multidrug transporter P-glycoprotein (Pgp) over 35 years ago in drug resistant cells prompted several decades of work attempting to overcome drug resistance by inhibition of drug efflux. Despite convincing laboratory data showing that drug transport can be inhibited in vitro, efforts to translate this discovery to the clinic have not succeeded. Since overexpression of Pgp and related transporters including ABCG2 and members of the ABCC family have been linked with poor outcome, it remains a reasonable hypothesis that this poor outcome is linked to reduction of drug exposure by efflux, and thus to drug resistance. In this review, we will discuss the question of whether ABC transporters mediate drug resistance in cancer through a reduction in drug accumulation in tumors, and whether the "Pgp inhibition hypothesis" might be wrong. The hypothesis, which holds that increased chemotherapy effectiveness can be achieved by inhibiting Pgp-mediated drug efflux has only been validated in model systems. Possible explanations for the failure to validate this clinically include the existence of other factors impacting of drug accumulation and uptake in tumors. Despite these difficulties, a potential role has emerged for drug transporters as therapeutic targets in the central nervous system (CNS). Both lines of investigation point to the need for imaging agents to facilitate the study of drug accumulation in human cancer. This is a critical need for targeted therapies, where an important dose-response relationship is likely to exist, and where drug resistance renders many of the novel targeted agents ineffective in a subset of patients. C1 [Robey, Robert W.; Massey, Paul R.; Amiri-Kordestani, Laleh; Bates, Susan E.] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Bates, SE (reprint author), NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA. EM sebates@helix.nih.gov NR 70 TC 47 Z9 49 U1 3 U2 11 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1871-5206 J9 ANTI-CANCER AGENT ME JI Anti-Cancer Agents Med. Chem. PD OCT PY 2010 VL 10 IS 8 BP 625 EP 633 PG 9 WC Oncology; Chemistry, Medicinal SC Oncology; Pharmacology & Pharmacy GA 734FD UT WOS:000288318500006 PM 21189132 ER PT J AU Walsh, TJ Driscoll, T Milligan, PA Wood, ND Schlamm, H Groll, AH Jafri, H Arrieta, AC Klein, NJ Lutsar, I AF Walsh, Thomas J. Driscoll, Timothy Milligan, Peter A. Wood, Nolan D. Schlamm, Haran Groll, Andreas H. Jafri, Hasan Arrieta, Antonio C. Klein, Nigel J. Lutsar, Irja TI Pharmacokinetics, Safety, and Tolerability of Voriconazole in Immunocompromised Children SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID INVASIVE FUNGAL-INFECTIONS; ANTIFUNGAL AGENT; INTRAVENOUS VORICONAZOLE; AMPHOTERICIN-B; ASPERGILLOSIS; EXPERIENCE; THERAPY; EPIDEMIOLOGY; MYCOSES AB The pharmacokinetics of voriconazole in children receiving 4 mg/kg intravenously (i.v.) demonstrate substantially lower plasma exposures (as defined by area under the concentration-time curve [AUC]) than those in adults receiving the same therapeutic dosage. These differences in pharmacokinetics between children and adults limit accurate prediction of pediatric voriconazole exposure based on adult dosages. We therefore studied the pharmacokinetics and tolerability of higher dosages of an i.v.-to-oral regimen of voriconazole in immunocompromised children aged 2 to <12 years in two dosage cohorts for the prevention of invasive fungal infections. The first cohort received 4 mg/kg i.v. every 12 h (q12h), then 6 mg/kg i.v. q12h, and then 4 mg/ kg orally (p.o.) q12h; the second received 6 mg/ kg i.v. q12h, then 8 mg/ kg i. v. q12h, and then 6 mg/ kg p.o. q12h. The mean values for the AUC over the dosing interval (AUC(tau)) for 4 mg/ kg and 6 mg/ kg i.v. in cohort 1 were 11,827 and 22,914 ng . h/ml, respectively, whereas the mean AUC(tau) values for 6 mg/ kg and 8 mg/ kg i.v. in cohort 2 were 17,249 and 29,776 ng . h/ml, respectively. High interpatient variability was observed. The bioavailability of the oral formulation in children was approximately 65%. The safety profiles were similar in the two cohorts and age groups. The most common treatment-related adverse event was increased gamma glutamyl transpeptidase levels. There was no correlation between adverse events and voriconazole exposure. In summary, voriconazole was tolerated to a similar degree regardless of dosage and age; the mean plasma AUC(tau) for 8 mg/ kg i. v. in children approached that for 4 mg/ kg i. v. in adults, thus representing a rationally selected dosage for the pediatric population. C1 [Walsh, Thomas J.] Cornell Univ, Weill Cornell Med Coll, Transplantat Oncol Infect Dis Program, New York, NY 10065 USA. [Walsh, Thomas J.] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. [Driscoll, Timothy] Duke Univ, Dept Pediat, Durham, NC 27706 USA. [Driscoll, Timothy] Duke Univ, Duke Clin Res Inst, Durham, NC USA. [Milligan, Peter A.; Schlamm, Haran; Lutsar, Irja] Pfizer Ltd, Sandwich CT13 9NJ, Kent, England. [Wood, Nolan D.; Schlamm, Haran] Pfizer Inc, New York, NY USA. [Groll, Andreas H.] Univ Munster, Munster, Germany. [Jafri, Hasan] Univ Texas SW Med Ctr Dallas, Simmons Canc Ctr, Dallas, TX 75390 USA. [Arrieta, Antonio C.] Childrens Hosp Orange Cty, Orange, CA 92668 USA. [Klein, Nigel J.] UCL, Inst Child Hlth, London, England. [Lutsar, Irja] Univ Tartu, Inst Med Microbiol, EE-50090 Tartu, Estonia. RP Walsh, TJ (reprint author), Cornell Univ, Weill Cornell Med Coll, Transplantat Oncol Infect Dis Program, 1300 York Ave,Rm A-21, New York, NY 10065 USA. EM thw2003@med.cornell.edu RI lutsar, irja/H-3177-2015 NR 29 TC 46 Z9 49 U1 1 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD OCT PY 2010 VL 54 IS 10 BP 4116 EP 4123 DI 10.1128/AAC.00896-10 PG 8 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 651EI UT WOS:000281907200011 PM 20660687 ER PT J AU Sala, C Dhar, N Hartkoorn, RC Zhang, M Ha, YH Schneider, P Cole, ST AF Sala, Claudia Dhar, Neeraj Hartkoorn, Ruben C. Zhang, Ming Ha, Young Hwan Schneider, Patricia Cole, Stewart T. TI Simple Model for Testing Drugs against Nonreplicating Mycobacterium tuberculosis SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID ATP HOMEOSTASIS; PERSISTENCE; INFECTION; LATENCY; ABSENCE; PA-824 AB Nonreplicating or dormant cells of Mycobacterium tuberculosis constitute a challenge to tuberculosis (TB) therapy because of their tolerance or phenotypic resistance to most drugs. Here, we propose a simple model for testing drugs against nongrowing cells that exploits the 18b strain of M. tuberculosis, a streptomycin (STR)-dependent mutant. Optimal conditions were established that allowed 18b cells to replicate in the presence of STR and to survive, but not multiply, following withdrawal of STR. In the presence of the antibiotic, M. tuberculosis 18b was susceptible to the currently approved TB drugs, isoniazid (INH) and rifampin (RIF), and to the experimental drugs TMC207, PA-824, meropenem (MER), benzothiazinone (BTZ), and moxifloxacin (MOXI). After STR depletion, the strain displayed greatly reduced susceptibility to the cell wall inhibitors INH and BTZ but showed increased susceptibility to RIF and PA-824, while MOXI and MER appeared equipotent under both conditions. The same potency ranking was found against nonreplicating M. tuberculosis 18b after in vivo treatment of chronically infected mice with five of these drugs. Despite the growth arrest, strain 18b retains significant metabolic activity in vitro, remaining positive in the resazurin reduction assay. Upon adaption to a 96-well format, this assay was shown to be suitable for high-throughput screening with strain 18b to find new inhibitors of dormant M. tuberculosis. C1 [Sala, Claudia; Dhar, Neeraj; Hartkoorn, Ruben C.; Zhang, Ming; Schneider, Patricia] Ecole Polytech Fed Lausanne, Global Hlth Inst, CH-1015 Lausanne, Switzerland. [Ha, Young Hwan] NIAID, TB Res Sect, LCID, NIH, Bethesda, MD 20892 USA. RP Cole, ST (reprint author), Ecole Polytech Fed Lausanne, Global Hlth Inst, Stn 19, CH-1015 Lausanne, Switzerland. EM stewart.cole@epfl.ch RI Dhar, Neeraj/K-8171-2013 OI Dhar, Neeraj/0000-0002-5887-8137 FU Leprosy and Tuberculosis of the New York Community Trust; Swiss National Science Foundation [31003A-125061]; European Commission [LHSP-CT-2005-018923, HEALTH-F3-2007-201762] FX R. C. Hartkoorn was the recipient of a postdoctoral fellowship from the Heiser Program for Research in Leprosy and Tuberculosis of the New York Community Trust. This work was funded in part by the Swiss National Science Foundation (31003A-125061) and the European Commission (LHSP-CT-2005-018923, HEALTH-F3-2007-201762). NR 35 TC 58 Z9 59 U1 0 U2 13 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD OCT PY 2010 VL 54 IS 10 BP 4150 EP 4158 DI 10.1128/AAC.00821-10 PG 9 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 651EI UT WOS:000281907200016 PM 20679505 ER PT J AU Gordon, O Slenters, TV Brunetto, PS Villaruz, AE Sturdevant, DE Otto, M Landmann, R Fromm, KM AF Gordon, Oliver Slenters, Tunde Vig Brunetto, Priscilla S. Villaruz, Amer E. Sturdevant, Daniel E. Otto, Michael Landmann, Regine Fromm, Katharina M. TI Silver Coordination Polymers for Prevention of Implant Infection: Thiol Interaction, Impact on Respiratory Chain Enzymes, and Hydroxyl Radical Induction SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID POLYSACCHARIDE INTERCELLULAR ADHESIN; HYDROGEN-PEROXIDE FORMATION; MUREIN HYDROLASE ACTIVITY; ESCHERICHIA-COLI; STAPHYLOCOCCUS-EPIDERMIDIS; ETHANEDIYL BIS(ISONICOTINATE); PENICILLIN TOLERANCE; BIOFILM FORMATION; JOINT INFECTIONS; AUREUS AB Prosthetic joint replacements are used increasingly to alleviate pain and improve mobility of the progressively older and more obese population. Implant infection occurs in about 5% of patients and entails significant morbidity and high social costs. It is most often caused by staphylococci, which are introduced perioperatively. They are a source of prolonged seeding and difficult to treat due to antibiotic resistance; therefore, infection prevention by prosthesis coating with nonantibiotic-type anti-infective substances is indicated. A renewed interest in topically used silver has fostered development of silver nanoparticles, which, however, present a potential health hazard. Here we present new silver coordination polymer networks with tailored physical and chemical properties as nanostructured coatings on metallic implant substrates. These compounds exhibited strong biofilm sugar-independent bactericidal activity on in vitro-grown biofilms and prevented murine Staphylococcus epidermidis implant infection in vivo with slow release of silver ions and limited transient leukocyte cytotoxicity. Furthermore, we describe the biochemical and molecular mechanisms of silver ion action by gene screening and by targeting cell metabolism of S. epidermidis at different levels. We demonstrate that silver ions inactivate enzymes by binding sulfhydryl (thiol) groups in amino acids and promote the release of iron with subsequent hydroxyl radical formation by an indirect mechanism likely mediated by reactive oxygen species. This is the first report investigating the global metabolic effects of silver in the context of a therapeutic application. We anticipate that the compounds presented here open a new treatment field with a high medical impact. C1 [Gordon, Oliver; Landmann, Regine] Univ Basel Hosp, Dept Biomed, CH-4056 Basel, Switzerland. [Slenters, Tunde Vig; Brunetto, Priscilla S.; Fromm, Katharina M.] Univ Fribourg, Dept Chem, CH-1700 Fribourg, Switzerland. [Villaruz, Amer E.; Otto, Michael] NIAID, NIH, Bethesda, MD 20892 USA. [Sturdevant, Daniel E.] NIAID, Res Technol Branch, Genom Unit, Rocky Mt Labs,NIH, Hamilton, MT 59840 USA. RP Landmann, R (reprint author), Univ Basel, Klingelbergstr 61, CH-4056 Basel, Switzerland. EM regine.landmann@unibas.ch; katharina.fromm@unifr.ch RI Carpenter, Dan/A-5404-2012; OI Otto, Michael/0000-0002-2222-4115 FU Swiss National Science Foundation [205320-121813]; NCCR Nano; FriMat; National Institute of Allergy and infectious Disease, U.S. National Institutes of Health FX This study was supported by the Swiss National Science Foundation (grant no. 205320-121813 to K.M.F.), the NCCR Nano, FriMat, and the Intramural Research Program of the National Institute of Allergy and Infectious Disease, U.S. National Institutes of Health (to M.O.). NR 50 TC 121 Z9 122 U1 8 U2 59 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 EI 1098-6596 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD OCT PY 2010 VL 54 IS 10 BP 4208 EP 4218 DI 10.1128/AAC.01830-09 PG 11 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 651EI UT WOS:000281907200023 PM 20660682 ER PT J AU Meng, H Zhang, RP Yang, HL Fan, Q Su, XZ Miao, J Cui, LW Yang, ZQ AF Meng, Hao Zhang, Rongping Yang, Henglin Fan, Qi Su, Xinzhuan Miao, Jun Cui, Liwang Yang, Zhaoqing TI In Vitro Sensitivity of Plasmodium falciparum Clinical Isolates from the China-Myanmar Border Area to Quinine and Association with Polymorphism in the Na+/H+ Exchanger SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID TRANSMEMBRANE PROTEIN PFCRT; CHLOROQUINE RESISTANCE; DRUG-RESISTANCE; MEFLOQUINE RESISTANCE; MULTIDRUG-RESISTANCE; PFMDR1 GENE; COPY NUMBER; MALARIA; MUTATIONS; THAILAND AB Quinine resistance (QNR) in Plasmodium falciparum has been detected in many regions of the world where malaria is endemic. Genetic polymorphisms in at least four genes are implicated in QN susceptibility, and their significance often depends on the genetic background of the parasites. In this study, we have culture-adapted 60 P. falciparum clinical isolates from the China-Myanmar border and assessed their in vitro responses to QN. Our results showed that >50% of the parasite isolates displayed reduced sensitivity to QN, with a half-maximal inhibitory concentration (IC50) above 500 nM. Genotyping of pfcrt found that an overwhelming proportion of the parasite population had the chloroquine-resistant genotype, whereas pfmdr1 mutation genotypes and gene amplification were rare. Genotyping of the P. falciparum Na+/H+ exchanger gene (pfnhe1) at the minisatellite ms4760 locus identified 10 haplotypes. Haplotype 7, which harbors three copies of the DNNND repeat, was the most predominant, accounting for nearly half of the parasite isolates. Correlation studies did not reveal significant associations of the polymorphisms in pfcrt and pfmdr1 genes with QN response. However, the ms4760 haplotypes were highly associated with in vitro QN responses. In particular, parasite isolates with an increased DNNND copy number tended to have significantly reduced QN susceptibility, whereas parasite isolates with a higher NHNDNHNNDDD copy number had increased QN susceptibility. This study provided further support for the importance of pfnhe1 polymorphisms in influencing QNR in P. falciparum. C1 [Miao, Jun; Cui, Liwang] Penn State Univ, Dept Entomol, University Pk, PA 16802 USA. [Meng, Hao; Fan, Qi; Yang, Zhaoqing] Kunming Med Univ, Dept Parasitol, Kunming 650500, Yunnan Province, Peoples R China. [Meng, Hao; Zhang, Rongping] Kunming Med Univ, Sch Pharmaceut Sci, Kunming 650500, Yunnan Province, Peoples R China. [Yang, Henglin] Yunnan Inst Parasit Dis, Puer 665000, Yunnan Province, Peoples R China. [Fan, Qi] Liaoning Acad Agr Sci, Dalian Inst Biotechnol, Dalian 116024, Liaoning Prov, Peoples R China. [Su, Xinzhuan] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. RP Cui, LW (reprint author), Penn State Univ, Dept Entomol, 501 ASI Bldg, University Pk, PA 16802 USA. EM luc2@psu.edu; zhaoqingy@yahoo.com RI Miao, Jun/F-5340-2010; OI Su, Xinzhuan/0000-0003-3246-3248 FU NIAID, NIH [1R01AI075429]; National Natural Science Foundation of China [30960050] FX This work was supported by 1R01AI075429 from NIAID, NIH, by the National Natural Science Foundation of China (no. 30960050). NR 51 TC 35 Z9 35 U1 1 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD OCT PY 2010 VL 54 IS 10 BP 4306 EP 4313 DI 10.1128/AAC.00321-10 PG 8 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 651EI UT WOS:000281907200034 PM 20643902 ER PT J AU Zhu, WM Murray, PR Huskins, WC Jernigan, JA McDonald, LC Clark, NC Anderson, KF McDougal, LK Hageman, JC Olsen-Rasmussen, M Frace, M Alangaden, GJ Chenoweth, C Zervos, MJ Robinson-Dunn, B Schreckenberger, PC Reller, LB Rudrik, JT Patel, JB AF Zhu, Wenming Murray, Patrick R. Huskins, W. Charles Jernigan, John A. McDonald, Lawrence C. Clark, Nancye C. Anderson, Karen F. McDougal, Linda K. Hageman, Jeff C. Olsen-Rasmussen, Melissa Frace, Mike Alangaden, George J. Chenoweth, Carol Zervos, Marcus J. Robinson-Dunn, Barbara Schreckenberger, Paul C. Reller, L. Barth Rudrik, James T. Patel, Jean B. TI Dissemination of an Enterococcus Inc18-Like vanA Plasmid Associated with Vancomycin-Resistant Staphylococcus aureus SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID SEX-PHEROMONE; STREPTOCOCCUS-FAECALIS; IDENTIFICATION; MICHIGAN; PIP501; AGGREGATION; PRECURSORS; EMERGENCE; SEQUENCES; BIOFILM AB Of the 9 vancomycin-resistant Staphylococcus aureus (VRSA) cases reported to date in the literature, 7 occurred in Michigan. In 5 of the 7 Michigan VRSA cases, an Inc18-like vanA plasmid was identified in the VRSA isolate and/or an associated vancomycin-resistant Enterococcus (VRE) isolate from the same patient. This plasmid may play a critical role in the emergence of VRSA. We studied the geographical distribution of the plasmid by testing 1,641 VRE isolates from three separate collections by PCR for plasmid-specific genes traA, repR, and vanA. Isolates from one collection (phase 2) were recovered from surveillance cultures collected in 17 hospitals in 13 states. All VRE isolates from 2 Michigan institutions (n = 386) and between 60 and 70 VRE isolates (n = 883) from the other hospitals were tested. Fifteen VRE isolates (3.9%) from Michigan were positive for an Inc18-like vanA plasmid (9 E. faecalis [12.5%], 3 E. faecium [1.0%], 2 E. avium, and 1 E. raffinosus). Six VRE isolates (0.6%) from outside Michigan were positive (3 E. faecalis [2.7%] and 3 E. faecium [0.4%]). Of all E. faecalis isolates tested, 6.0% were positive for the plasmid, compared to 0.6% for E. faecium and 3.0% for other spp. Fourteen of the 15 plasmid-positive isolates from Michigan had the same Tn1546 insertion site location as the VRSA-associated Inc18-like plasmid, whereas 5 of 6 plasmid-positive isolates from outside Michigan differed in this characteristic. Most plasmid-positive E. faecalis isolates demonstrated diverse patterns by PFGE, with the exception of three pairs with indistinguishable patterns, suggesting that the plasmid is mobile in nature. Although VRE isolates with the VRSA-associated Inc18-like vanA plasmid were more common in Michigan, they remain rare. Periodic surveillance of VRE isolates for the plasmid may be useful in predicting the occurrence of VRSA. C1 [Zhu, Wenming; Jernigan, John A.; McDonald, Lawrence C.; Clark, Nancye C.; Anderson, Karen F.; McDougal, Linda K.; Hageman, Jeff C.; Patel, Jean B.] Ctr Dis Control & Prevent, Div Healthcare Qual Promot, Atlanta, GA 30333 USA. [Olsen-Rasmussen, Melissa; Frace, Mike] Ctr Dis Control & Prevent, Div Sci Resources, Atlanta, GA 30333 USA. [Murray, Patrick R.] Natl Inst Hlth Clin Ctr, Bethesda, MD USA. [Huskins, W. Charles] Mayo Clin, Coll Med, Rochester, MN USA. [Alangaden, George J.] Detroit Med Ctr, Detroit, MI USA. [Chenoweth, Carol] Univ Michigan, Ann Arbor, MI 48109 USA. [Zervos, Marcus J.] Henry Ford Hosp, Detroit, MI 48202 USA. [Robinson-Dunn, Barbara] William Beaumont Hosp, Royal Oak, MI 48072 USA. [Schreckenberger, Paul C.] Loyola Univ, Ctr Med, Maywood, IL 60153 USA. [Reller, L. Barth] Duke Univ, Med Ctr, Durham, NC USA. [Rudrik, James T.] Michigan Dept Community Hlth, Lansing, MI USA. RP Zhu, WM (reprint author), Ctr Dis Control & Prevent, Div Healthcare Qual Promot, 1600 Clifton Rd,MS G08, Atlanta, GA 30333 USA. EM waz7@cdc.gov; vzp4@cdc.gov OI Huskins, W. Charles/0000-0002-9989-175X NR 33 TC 46 Z9 46 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD OCT PY 2010 VL 54 IS 10 BP 4314 EP 4320 DI 10.1128/AAC.00185-10 PG 7 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 651EI UT WOS:000281907200035 PM 20660665 ER PT J AU Chen, WZ Xiao, XD Wang, YP Zhu, ZY Dimitrov, DS AF Chen, Weizao Xiao, Xiaodong Wang, Yanping Zhu, Zhongyu Dimitrov, Dimiter S. TI Bifunctional fusion proteins of the human engineered antibody domain m36 with human soluble CD4 are potent inhibitors of diverse HIV-1 isolates SO ANTIVIRAL RESEARCH LA English DT Article DE HIV-1; Engineered antibody domain; Soluble CD4; Fusion protein; Half life; Effector function ID IMMUNODEFICIENCY-VIRUS TYPE-1; GP120 ENVELOPE GLYCOPROTEIN; HUMAN MONOCLONAL-ANTIBODIES; CORECEPTOR-BINDING-SITE; TYROSINE SULFATION; NEUTRALIZATION; RECEPTOR; SCD4-17B; COMPLEX AB Currently used antiretroviral therapy is highly successful but there is still a need for new effective and safe prophylactics and therapeutics. We have previously identified and characterized a human engineered antibody domain (eAd), m36, which exhibits potent broadly neutralizing activity against HIV-1 by targeting a highly conserved CD4 binding-induced (CD4i) structure on the viral envelope glycoprotein (Env) gp120. m36 has very small size (similar to 15 kDa) but is highly specific and is likely to be safe in long-term use thus representing a novel class of potentially promising HIV-1 inhibitors. Major problems with the development of m36 as a candidate therapeutic are possible short serum half life and lack of effector functions that could be important for effective protection in vivo. Fusion of m36 to human IgG1 Fc resulted in dramatically diminished neutralization potency most likely due to the sterically restricted nature of the m36 epitope that limits access of large molecules. To confer effector functions and simultaneously increase the potency, we first matured m36 by panning and screening a mutant library for mutants with increased binding to gp120. We next fused m36 and its mutants with the first two domains (soluble CD4, sCD4) of the human CD4 using a polypeptide linker. Our results showed that the selected m36 mutants and the sCD4 fusion proteins exhibited more potent antiviral activities than m36. The m36-sCD4 fusion proteins with human IgG1 Fc showed even higher potency likely due to their bivalency and increased avidity although with a greater increase in molecular size. Our data suggest that m36 derivatives are promising HIV-1 candidate therapeutics and tools to study highly conserved gp120 structures with implications for understanding mechanisms of entry and design of vaccine immunogens and small-molecule inhibitors. Published by Elsevier B.V. C1 [Chen, Weizao] NCI Frederick, Prot Interact Grp, CCRNP, CCR,NIH, Frederick, MD 21702 USA. [Wang, Yanping; Zhu, Zhongyu] Sci Applicat Int Corp Frederick Inc, Basic Res Program, Frederick, MD 21702 USA. RP Chen, WZ (reprint author), NCI Frederick, Prot Interact Grp, CCRNP, CCR,NIH, Bldg 469,Rm 144, Frederick, MD 21702 USA. EM chenw3@mail.nih.gov FU National Institutes of Health (NIH); NIH, National Cancer Institute, Center for Cancer Research; National Cancer Institute, NIH [N01-CO-12400]; Gates Foundation FX We thank Christopher Broder, Gerald Quinnan, Dennis Burton, Barton Haynes and Tim Fouts for providing reagents. This project was supported by the Intramural AIDS Targeted Antiviral Program of the National Institutes of Health (NIH), by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research, by federal funds from the National Cancer Institute, NIH, under contract N01-CO-12400, and by the Gates Foundation (D.S.D.). NR 23 TC 18 Z9 18 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD OCT PY 2010 VL 88 IS 1 BP 107 EP 115 DI 10.1016/j.antiviral.2010.08.004 PG 9 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA 669ZH UT WOS:000283388400014 PM 20709110 ER PT J AU Zhang, DM Vangala, K Jiang, DP Zou, SG Pechan, T AF Zhang, Dongmao Vangala, Karthikeshwar Jiang, Dongping Zou, Sige Pechan, Tibor TI Drop Coating Deposition Raman Spectroscopy of Fluorescein Isothiocyanate Labeled Protein SO APPLIED SPECTROSCOPY LA English DT Article DE Fluorescein isothiocyanate; FITC; Bovine serum albumin; BSA; Drop coating deposition Raman sampling; DCDR; Photobleaching; Fluorescence; Protein-dye conjugation ID BOVINE SERUM-ALBUMIN; ABSORPTION-COEFFICIENT; MAGNETIC PARTICLES; ENERGY-TRANSFER; SURFACE; SPECTRA; QUANTIFICATION; MICROSCOPY; MOLECULES; RATIO AB Using bovine serum albumin (BSA) as the model protein, normal Raman spectra of fluorescein isothiocyanate (FITC) conjugated protein were systematically studied for the first time using both solution and the drop coating deposition Raman (DCDR) sampling techniques. The FITC-BSA Raman spectra are dominated by the FITC Raman features that are strongly pH dependent. Current DCDR detection sensitivity obtained with a 10:1 FITC-BSA conjugate is 45 fmol in terms of total protein consumption and similar to 15 attomol at laser probed volume. Unlike the FITC BSA solution Raman spectra, where the FITC Raman features are photostable, concurrent FITC fluorescence and Raman photobleaching is observed in the DCDR spectra of FITC-BSA. While the FITC Raman photobleaching follows a single exponential decay function with a time constant independent of the FITC labeling ratio, the fluorescence background photobleaching is much more complicated and it depends strongly on the FITC labeling ratio and sample conditions. Mechanistically, the FITC Raman photobleaching is believed to be due to photochemical reaction of the FITC molecules in the electronically excited state. The FITC fluorescence photobleaching involves both concentration quenching and photochemical quenching, and the latter may involve a photochemical intermediate that is fluorescence inactive but Raman active. C1 [Zhang, Dongmao; Vangala, Karthikeshwar; Jiang, Dongping] Mississippi State Univ, Dept Chem, Mississippi State, MS 39762 USA. [Zou, Sige] NIA, NIH, Baltimore, MD 21224 USA. [Pechan, Tibor] Mississippi State Univ, Life Sci & Biotechnol Inst, Mississippi State, MS 39762 USA. RP Zhang, DM (reprint author), Mississippi State Univ, Dept Chem, Mississippi State, MS 39762 USA. EM dz33@msstate.edu FU Mississippi State University; National Institute on Aging, NIH FX This work was supported in part by start-up funding provided to D.M.Z. from Mississippi State University, and by the Intramural Research Program of the National Institute on Aging, NIH, to S.Z. The authors thank Ms. Laura Lewis for editorial assistance. NR 48 TC 6 Z9 6 U1 4 U2 35 PU SOC APPLIED SPECTROSCOPY PI FREDERICK PA 5320 SPECTRUM DRIVE SUITE C, FREDERICK, MD 21703 USA SN 0003-7028 J9 APPL SPECTROSC JI Appl. Spectrosc. PD OCT PY 2010 VL 64 IS 10 BP 1078 EP 1085 PG 8 WC Instruments & Instrumentation; Spectroscopy SC Instruments & Instrumentation; Spectroscopy GA 663AN UT WOS:000282855500002 PM 20925976 ER PT J AU Baykal, D Irrechukwu, O Lin, PC Fritton, K Spencer, RG Pleshko, N AF Baykal, Doruk Irrechukwu, Onyi Lin, Ping-Chang Fritton, Kate Spencer, Richard G. Pleshko, Nancy TI Nondestructive Assessment of Engineered Cartilage Constructs Using Near-Infrared Spectroscopy SO APPLIED SPECTROSCOPY LA English DT Article DE Near-infrared spectroscopy; NIR spectroscopy; Fourier transform infrared spectroscopy; FT-IR spectroscopy; Partial least squares; PLS; Multivariate analysis; Cartilage; Tissue engineering ID AUTOLOGOUS CHONDROCYTE IMPLANTATION; ARTICULAR-CARTILAGE; MAGNETIZATION-TRANSFER; NIR SPECTROSCOPY; TISSUE; COLLAGEN; MRI; WATER; KNEE; T-2 AB Noninvasive assessment of engineered cartilage properties would enable better control of the developing tissue towards the desired structural and compositional endpoints through optimization of the biochemical environment in real time. The objective of this study is to assess the matrix constituents of cartilage using near-infrared spectroscopy (NIRS), a technique that permits full-depth assessment of developing engineered tissue constructs. Mid-infrared (mid-IR) and NIR data were acquired from full-thickness cartilage constructs that were grown up to 4 weeks with and without mechanical stimulation. Correlations were assessed between established mid-IR peak areas that reflect the relative amount of collagen (amide I, amide II, and 1338 cm(-1)) and proteoglycan (PG), (850 cm(-1)), and the integrated area of the NIR water absorbance at 5190 cm(-1). This analysis was performed to evaluate whether simple assessment of the NIR water absorbance could yield information about matrix development. It was found that an increase in the mid-IR PG absorbance at 850 cm(-1) correlated with the area of the NIR water peak (Spearman's rho = 0.95, p < 0.0001). In the second analysis, a partial least squares method (PLSI) was used to assess whether an extended NIR spectral range (5400-3800 cm(-1)) could be utilized to predict collagen and proteoglycan content of the constructs based on mid-IR absorbances. A subset of spectra was randomly selected as an independent prediction set in this analysis. Average of the normalized root mean square errors of prediction of first-derivative NIR spectral models were 7% for 850 cm(-1) (PG), 11% for 1338 cm(-1) (collagen), 8% for amide II (collagen), and 8% for amide I (collagen). These results demonstrate the ability of NIRS to monitor macromolecular content of cartilage constructs and is the first step towards employing NIR to assess engineered cartilage in situ. C1 [Pleshko, Nancy] Temple Univ, Philadelphia, PA 19122 USA. [Baykal, Doruk] Drexel Univ, Philadelphia, PA 19104 USA. [Irrechukwu, Onyi; Lin, Ping-Chang; Spencer, Richard G.] NIA, NIH, Baltimore, MD 21224 USA. [Fritton, Kate] Exponent Inc, Philadelphia, PA 19104 USA. RP Pleshko, N (reprint author), Temple Univ, Philadelphia, PA 19122 USA. EM npleshko@temple.edu OI Lin, Ping-Chang/0000-0003-0918-4072 FU NIH [EB000744, AR056145]; NIH National Institute on Aging FX This study was supported by NIH EB000744, AR056145, and in part by the Intramural Research Program of the NIH National Institute on Aging. NR 50 TC 24 Z9 25 U1 2 U2 14 PU SOC APPLIED SPECTROSCOPY PI FREDERICK PA 5320 SPECTRUM DRIVE SUITE C, FREDERICK, MD 21703 USA SN 0003-7028 J9 APPL SPECTROSC JI Appl. Spectrosc. PD OCT PY 2010 VL 64 IS 10 BP 1160 EP 1166 PG 7 WC Instruments & Instrumentation; Spectroscopy SC Instruments & Instrumentation; Spectroscopy GA 663AN UT WOS:000282855500013 PM 20925987 ER PT J AU Nicodemus, KK Law, AJ Radulescu, E Luna, A Kolachana, B Vakkalanka, R Rujescu, D Giegling, I Straub, RE McGee, K Gold, B Dean, M Muglia, P Callicott, JH Tan, HY Weinberger, DR AF Nicodemus, Kristin K. Law, Amanda J. Radulescu, Eugenia Luna, Augustin Kolachana, Bhaskar Vakkalanka, Radhakrishna Rujescu, Dan Giegling, Ina Straub, Richard E. McGee, Kate Gold, Bert Dean, Michael Muglia, Pierandrea Callicott, Joseph H. Tan, Hao-Yang Weinberger, Daniel R. TI Biological Validation of Increased Schizophrenia Risk With NRG1, ERBB4, and AKT1 Epistasis via Functional Neuroimaging in Healthy Controls SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID NITRIC-OXIDE SYNTHASE; NO SIGNIFICANT ASSOCIATION; FAMILY-BASED ASSOCIATION; NEUREGULIN-1 GENE; INTERMEDIATE PHENOTYPES; JAPANESE POPULATION; SCOTTISH POPULATION; SUSCEPTIBILITY GENE; EUROPEAN-ANCESTRY; WORKING-MEMORY AB Context: NRG1 is a schizophrenia candidate gene and plays an important role in brain development and neural function. Schizophrenia is a complex disorder, with etiology likely due to epistasis. Objective: To examine epistasis between NRG1 and selected N-methyl-D-aspartate glutamate pathway partners implicated in its effects, including ERBB4, AKT1, DLG4, NOS1, and NOS1AP. Design: Schizophrenia case-control sample analyzed using machine learning algorithms and logistic regression with follow-up using neuroimaging on an independent sample of healthy controls. Participants: A referred sample of schizophrenic patients (n = 296) meeting DSM-IV criteria for schizophrenia spectrum disorder and a volunteer sample of controls for case-control comparison (:1 = 365) and a separate volunteer sample of controls for neuroimaging (n=172). Main Outcome Measures: Epistatic association between single-nucleotide polymorphisms (SNPs) and case-control status; epistatic association between SNPs and the blood oxygen level dependent physiological response during working memory measured by functional magnetic resonance imaging. Results: We observed interaction between NRG1 5' and 3' SNPs rs4560751 and rs3802160 (likelihood ratio test P=.00020) and schizophrenia, which was validated using functional magnetic resonance imaging of working memory in healthy controls; carriers of risk-associated genotypes showed inefficient processing in the dorsolateral prefrontal cortex (P=.015, familywise error corrected). We observed epistasis between NRG1 (rs10503929; Thr286/289/294Met) and its receptor ERBB4 (rs1026882; likelihood ratio test P=.035); a 3-way interaction with these 2 SNPs and AKT1 (rs2494734) was also observed (odds ratio, 27.13; 95% confidence interval, 3.30-223.03; likelihood ratio test P=.042). These same 2-and 3-way interactions were further biologically validated via functional magnetic resonance imaging: healthy individuals carrying risk genotypes for NRG1 and ERBB4, or these 2 together with AKT1, were disproportionately less efficient in dorsolateral prefrontal cortex processing. Lower-level interactions were not observed between NRG1/ERBB4 and AKT1 in association or neuroimaging, consistent with biological evidence that NRG1 X ERBB4 interaction modulates downstream AKT1 signaling. Conclusion: Our data suggest complex epistatic effects implicating an NRG1 molecular pathway in cognitive brain function and the pathogenesis of schizophrenia. Arch Gen Psychiatry. 2010;67(10):991-1001 C1 [Nicodemus, Kristin K.; Law, Amanda J.; Radulescu, Eugenia; Luna, Augustin; Kolachana, Bhaskar; Vakkalanka, Radhakrishna; Straub, Richard E.; Callicott, Joseph H.; Tan, Hao-Yang; Weinberger, Daniel R.] NIMH, Genes Cognit & Psychosis Program, Intramural Res Program, NIH, Bethesda, MD 20892 USA. [Nicodemus, Kristin K.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. [Nicodemus, Kristin K.] Univ Oxford, Dept Clin Pharmacol, Oxford, England. [Law, Amanda J.] Univ Oxford, Warneford Hosp, Dept Psychiat, Oxford, England. [Rujescu, Dan; Giegling, Ina] Univ Munich, Dept Psychiat, Sect Mol & Clin Neurobiol, D-8000 Munich, Germany. [McGee, Kate; Gold, Bert; Dean, Michael] NCI, Expt Immunol Lab, Frederick, MD 21701 USA. [Muglia, Pierandrea] GlaxoSmithKline Inc, Verona, Italy. RP Weinberger, DR (reprint author), NIMH, Genes Cognit & Psychosis Program, Intramural Res Program, NIH, Room 4S-235,10 Ctr Dr, Bethesda, MD 20892 USA. EM weinberd@mail.nih.gov RI Law, Amanda/G-6372-2012; Callicott, Joseph/C-9102-2009 OI Callicott, Joseph/0000-0003-1298-3334 FU GlaxoSmithKline; National Institute of Mental Health FX Financial Disclosure: Dr Muglia is a full-time employee of GlaxoSmithKline, who have filed patent applications for SNPs associated with schizophrenia (US patent applications 20080176239 and 20080176240 and international application number PCT/EP2008/050477). The recruitment of the German patients was partially supported by GlaxoSmithKline.; Funding/Support: This work was supported by the National Institute of Mental Health Intramural Research Program. Dr Law, is a Medical Research Council UK Career Development Fellow. NR 58 TC 69 Z9 70 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD OCT PY 2010 VL 67 IS 10 BP 991 EP 1001 PG 11 WC Psychiatry SC Psychiatry GA 663VD UT WOS:000282917400002 PM 20921115 ER PT J AU Umhau, JC Momenan, R Schwandt, ML Singley, E Lifshitz, M Doty, L Adams, LJ Vengeliene, V Spanagel, R Zhang, Y Shen, J George, DT Hommer, D Heilig, M AF Umhau, John C. Momenan, Reza Schwandt, Melanie L. Singley, Erich Lifshitz, Marie Doty, Linda Adams, Lauren J. Vengeliene, Valentina Spanagel, Rainer Zhang, Yan Shen, Jun George, David T. Hommer, Daniel Heilig, Markus TI Effect of Acamprosate on Magnetic Resonance Spectroscopy Measures of Central Glutamate in Detoxified Alcohol-Dependent Individuals A Randomized Controlled Experimental Medicine Study SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID CORTICOTROPIN-RELEASING-FACTOR; AMINOBUTYRIC-ACID LEVELS; BINGE ETHANOL EXPOSURE; AMINO-ACIDS; WITHDRAWAL; BRAIN; CONSUMPTION; DEPRESSION; SYSTEM; GLUTAMATE/GLUTAMINE AB Context: Acamprosate is approved for the treatment of alcoholism, but its mechanism of action remains unclear. Results of animal studies suggest that a persistent hyperglutamatergic state contributes to the pathogenesis of alcoholism and that acamprosate may exert its actions by intervening in this process. Human translation of these findings is lacking. Objective: To examine whether acamprosate modulates indices of central glutamate levels in recently abstinent alcohol-dependent patients as measured using proton nuclear magnetic resonance spectroscopy ((1)H-MRS). Design: A 4-week, double-blind, placebo-controlled, randomized controlled experimental medicine study, with (1)H-MRS measures obtained on days 4 and 25. Setting: An inpatient research unit at the NIH Clinical Center. Patients: Thirty-three patients who met the DSM-IV criteria for alcohol dependence and who were admitted for medically supervised withdrawal from ongoing alcohol use. Intervention: Four weeks of acamprosate (initial oral loading followed by 1998 mg daily) or 'matched placebo, initiated at the time of admission. Main Outcome Measures: The glutamate to creatine ratio as determined using single-voxel (1)H-MRS in the anterior cingulate. Exploratory neuroendocrine, biochemical, and behavioral outcomes were also collected, as were safety- and tolerability-related measures. Results: There was a highly significant suppression of the glutamate to creatine ratio across time by acamprosate (time X treatment interaction: F(1,29)= 13.5, P<.001). Cerebrospinal fluid levels of glutamate obtained in a subset of patients 4 weeks into abstinence were uncorrelatecl with the MRS measures and unaffected by treatment but were strongly correlated (R(2)=0.48, P<.001) with alcohol dependence severity. Other exploratory outcomes, including repeated dexamethasone corticotropin-releasing hormone tests, and psychiatric ratings were unaffected. Among tolerability measures, gastrointestinal symptoms were significantly greater in acamprosate-treated individuals, in agreement with the established profile of acamprosate. Conclusion: The MRS measures of central glutamate are reduced across time when acamprosate therapy is initiated at the onset of alcohol abstinence. C1 [Heilig, Markus] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD 20892 USA. [Vengeliene, Valentina; Spanagel, Rainer] Cent Inst Mental Hlth, Dept Psychopharmacol, D-6800 Mannheim, Germany. [Zhang, Yan; Shen, Jun] NIMH, Bethesda, MD 20892 USA. RP Heilig, M (reprint author), NIAAA, Lab Clin & Translat Studies, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA. EM markus.heilig@mail.nih.gov RI Schwandt, Melanie/L-9866-2016 FU National Institute on Alcohol Abuse and Alcoholism FX Funding/Support: This study was supported by intramural research funding from the National Institute on Alcohol Abuse and Alcoholism. NR 45 TC 55 Z9 56 U1 0 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD OCT PY 2010 VL 67 IS 10 BP 1069 EP 1077 PG 9 WC Psychiatry SC Psychiatry GA 663VD UT WOS:000282917400011 PM 20921123 ER PT J AU Kitano, H Kageyama, SI Hewitt, SM Hayashi, R Doki, Y Ozaki, Y Fujino, S Takikita, M Kubo, H Fukuoka, J AF Kitano, Haruhisa Kageyama, Shun-Ichiro Hewitt, Stephen M. Hayashi, Ryuji Doki, Yoshinori Ozaki, Yoshitomo Fujino, Shozo Takikita, Mikiko Kubo, Hajime Fukuoka, Junya TI Podoplanin Expression in Cancerous Stroma Induces Lymphangiogenesis and Predicts Lymphatic Spread and Patient Survival SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID CELL LUNG-CANCER; INVASIVE BREAST-CARCINOMA; CENTRAL-NERVOUS-SYSTEM; PROGNOSTIC-FACTOR; POOR-PROGNOSIS; COLORECTAL-CARCINOMA; ENHANCED EXPRESSION; MICROVESSEL DENSITY; TISSUE MICROARRAYS; MARKER PODOPLANIN AB Context.-Podoplanin is a mucin-type glycoprotein and a lymphatic endothelial marker. Immunohistochemical staining for podoplanin is currently used as a routine pathologic diagnosis tool in Japan to identify lymphatic invasion of cancer cells. Recent reports suggest that podoplanin and other proangiogenic molecules are expressed in stromal fibroblasts and myofibroblasts. Objective.-To analyze the distribution of podoplanin expression in tumor stroma and its clinical and biologic significance. Design.-We performed immunohistochemistry for podoplanin on tissue microarrays from 1350 cases of 14 common cancer types. Results.-Two hundred eighty-seven of 662 cases (43%) showed podoplanin expression in the stromal cells within cancer nests. Stromal podoplanin expression in 14 common cancer types was significantly associated with tumor stage (P < .001), lymph node metastases (P < .001), lymphatic invasion (P = .02), and venous invasion (P < .001). The stromal cells positive for podoplanin were also positive for alpha-smooth muscle actin but negative for desmin, confirming a myofibroblasts phenotype. In contrast, myofibroblasts in inflammatory fibrotic lung diseases were podoplanin negative. Lymphatic vessel density was greater in the stromas with podoplanin expression than in the stroma lacking podoplanin-expressing stromal cells (P = .01). Survival data were available for non-small cell lung cancer. Stromal podoplanin expression was associated with poorer prognosis in adenocarcinoma (P < .001) and remains statistically significant after adjustment for sex, age, and stage (P = .01). Conclusion.-Our data indicate that podoplanin expression in stromal myofibroblasts may function as a proangiogenic biomarker and may serve as a predictive marker of lymphatic/vascular spread of cancer cells and a prognostic marker of patient survival. (Arch Pathol Lab Med. 2010;134:1520-1527) C1 [Kitano, Haruhisa; Kageyama, Shun-Ichiro; Fukuoka, Junya] Toyama Univ Hosp, Pathol Lab, Toyama 9300194, Japan. [Kitano, Haruhisa; Ozaki, Yoshitomo; Fujino, Shozo] Shiga Univ Med Sci, Dept Surg, Otsu, Shiga 52021, Japan. [Hewitt, Stephen M.; Takikita, Mikiko] NCI, Tissue Array Res Program, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Hayashi, Ryuji] Toyama Univ, Dept Internal Med, Toyama 930, Japan. [Doki, Yoshinori] Toyama Univ, Dept Surg, Toyama 930, Japan. [Kubo, Hajime] Kyoto Univ Hosp, Dept Surg, Div Gastrointestinal Surg, Kyoto 606, Japan. RP Fukuoka, J (reprint author), Toyama Univ Hosp, Toyama Tissue Microarray Lab, Dept Surg Pathol, 2630 Sugitani, Toyama 9300194, Japan. EM fukuokaj@med.u-toyama.ac.jp OI Hewitt, Stephen/0000-0001-8283-1788 FU Japanese Ministry of Health, Labor and Welfare FX We express our gratitude for technical support given by our excellent technicians: Mr Takashi Hori, MT, MS, Satoshi Ejiri, MT, and Yuta Sakai, MT, and Ms Naoko Kumagai, MS, Chieko Kiya, MT, and Kanako Nakagawa, MT. We also like to thank Ms Noriko Kanamori, BA, for her huge contribution of composing the TMA. We also appreciate Drs Kazuhiro Nomoto, MD, PhD, Masakiyo Sasahara, MD, PhD, and Yasuo Takano, MD, PhD, for their support. This work was partly funded by the Japanese Ministry of Health, Labor and Welfare. NR 50 TC 34 Z9 36 U1 0 U2 4 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD OCT PY 2010 VL 134 IS 10 BP 1520 EP 1527 PG 8 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 661UQ UT WOS:000282754100019 PM 20923309 ER PT J AU Shin, EJ Hong, JS Kim, HC AF Shin, Eun-Joo Hong, Jau-Shyong Kim, Hyoung-Chun TI Neuropsychopharmacological Understanding for Therapeutic Application of Morphinans SO ARCHIVES OF PHARMACAL RESEARCH LA English DT Review DE Dextromethorphan and its analogs; Naloxone; Neuroprotective effects; Neuropsychotoxicity ID METHYL-D-ASPARTATE; NIGRAL DOPAMINERGIC-NEURONS; MICROGLIAL NADPH-OXIDASE; SIGMA-BINDING-SITES; GUINEA-PIG BRAIN; KAINIC ACID; PARKINSONS-DISEASE; OPIOID RECEPTORS; INDUCED SEIZURES; RAT HIPPOCAMPUS AB Morphinans are a class of compounds containing the basic structure of morphine. It is well-known that morphinans possess diverse pharmacological effects on the central nervous system. This review will demonstrate novel neuroprotective effects of several morphinans such as, dextromethorphan, its analogs and naloxone on the models of multiple neurodegenerative disease by modulating glial activation associated with the production of a host of proinflammatory and neurotoxic factors, although dextromethorphan possesses neuropsycotoxic potentials. The neuroprotective effects and the therapeutic potential for the treatment of excitotoxic and inflammatory neurodegenerative diseases, and underlying mechanism of morphinans are discussed. C1 [Shin, Eun-Joo; Kim, Hyoung-Chun] Kangwon Natl Univ, Neuropsychopharmacol & Toxicol Program, Coll Pharm, Chunchon 200701, South Korea. [Hong, Jau-Shyong] NIEHS, Neuropharmacol Sect, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. RP Kim, HC (reprint author), Kangwon Natl Univ, Neuropsychopharmacol & Toxicol Program, Coll Pharm, Chunchon 200701, South Korea. EM kimhc@kangwon.ac.kr OI Kim, Hyoung-Chun/0000-0003-0420-795X FU Ministry of Science and Technology, Republic of Korea [2010K00812] FX This study was supported by a grant from the Brain Research Center from 21st Century Frontier Research Program (# 2010K00812) funded by the Ministry of Science and Technology, Republic of Korea. NR 99 TC 1 Z9 1 U1 0 U2 4 PU PHARMACEUTICAL SOC KOREA PI SEOUL PA 1489-3 SUHCHO-DONG, SUHCHO-KU, SEOUL 137-071, SOUTH KOREA SN 0253-6269 J9 ARCH PHARM RES JI Arch. Pharm. Res. PD OCT PY 2010 VL 33 IS 10 SI SI BP 1575 EP 1587 DI 10.1007/s12272-010-1009-4 PG 13 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 672DM UT WOS:000283563200011 PM 21052935 ER PT J AU Anzinger, JJ Chang, J Xu, Q Buono, C Li, YF Leyva, FJ Park, BC Greene, LE Kruth, HS AF Anzinger, Joshua J. Chang, Janet Xu, Qing Buono, Chiara Li, Yifu Leyva, Francisco J. Park, Bum-Chan Greene, Lois E. Kruth, Howard S. TI Native Low-Density Lipoprotein Uptake by Macrophage Colony-Stimulating Factor-Differentiated Human Macrophages Is Mediated by Macropinocytosis and Micropinocytosis SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE atherosclerosis; macrophages; LDL; macropinocytosis; micropinocytosis ID MONOCYTE-DERIVED MACROPHAGES; FLUID-PHASE PINOCYTOSIS; FOAM CELL-FORMATION; HORSERADISH-PEROXIDASE; CULTURED-CELLS; H+-ATPASE; ATHEROSCLEROTIC LESIONS; ALVEOLAR MACROPHAGES; ENDOCYTIC PATHWAY; MOUSE MACROPHAGES AB Objective-To examine the pinocytotic pathways mediating native low-density lipoprotein (LDL) uptake by human macrophage colony-stimulating factor-differentiated macrophages (the predominant macrophage phenotype in human atherosclerotic plaques). Methods and Results-We identified the kinase inhibitor SU6656 and the Rho GTPase inhibitor toxin B as inhibitors of macrophage fluid-phase pinocytosis of LDL. Assessment of macropinocytosis by time-lapse microscopy revealed that both drugs almost completely inhibited macropinocytosis, although LDL uptake and cholesterol accumulation by macrophages were only partially inhibited (approximately 40%) by these agents. Therefore, we investigated the role of micropinocytosis in mediating LDL uptake in macrophages and identified bafilomycin A1 as an additional partial inhibitor (approximately 40%) of macrophage LDL uptake that targeted micropinocytosis. When macrophages were incubated with both bafilomycin A1 and SU6656, inhibition of LDL uptake was additive (reaching 80%), showing that these inhibitors target different pathways. Microscopic analysis of fluid-phase uptake pathways in these macrophages confirmed that LDL uptake occurs through both macropinocytosis and micropinocytosis. Conclusion-Our findings show that human macrophage colony-stimulating factor-differentiated macrophages take up native LDL by macropinocytosis and micropinocytosis, underscoring the importance of both pathways in mediating LDL uptake by these cells. (Arterioscler Thromb Vasc Biol. 2010;30:2022-2031.) C1 [Anzinger, Joshua J.; Chang, Janet; Xu, Qing; Buono, Chiara; Li, Yifu; Leyva, Francisco J.; Kruth, Howard S.] NHLBI, Expt Atherosclerosis Sect, NIH, Bethesda, MD 20892 USA. [Park, Bum-Chan; Greene, Lois E.] NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Kruth, HS (reprint author), NHLBI, Expt Atherosclerosis Sect, NIH, Bldg 10,Room 5N-113,10 Ctr Dr,MSC 1422, Bethesda, MD 20892 USA. EM kruthh@nhlbi.nih.gov FU National Heart, Lung, and Blood Institute, National Institutes of Health FX This study was supported by the Intramural Research Program, National Heart, Lung, and Blood Institute, National Institutes of Health. NR 62 TC 25 Z9 25 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD OCT PY 2010 VL 30 IS 10 BP 2022 EP U318 DI 10.1161/ATVBAHA.110.210849 PG 31 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 650VV UT WOS:000281882800023 PM 20634472 ER PT J AU Reis, JP Loria, CM Steffen, LM Zhou, X van Horn, L Siscovick, DS Jacobs, DR Carr, JJ AF Reis, Jared P. Loria, Catherine M. Steffen, Lyn M. Zhou, Xia van Horn, Linda Siscovick, David S. Jacobs, David R., Jr. Carr, J. Jeffrey TI Coffee, Decaffeinated Coffee, Caffeine, and Tea Consumption in Young Adulthood and Atherosclerosis Later in Life The CARDIA Study SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE antioxidants; atherosclerosis; calcification; carotid arteries; diet; epidemiology; nutrition ID CORONARY-HEART-DISEASE; REVERSES ENDOTHELIAL DYSFUNCTION; LOW-DENSITY-LIPOPROTEIN; E-DEFICIENT MICE; CARDIOVASCULAR-DISEASE; BLOOD-PRESSURE; MYOCARDIAL-INFARCTION; ARTERY-DISEASE; RISK-FACTOR; GREEN AB Objective-To determine the association of coffee, decaffeinated coffee, caffeine, and tea consumption in young adulthood with the presence and progression of coronary artery calcified (CAC) plaque and carotid intima-media thickness later in life. Methods and Results-The Coronary Artery Risk Development in Young Adults (CARDIA) Study is a cohort of 5115 white and black adults who were aged 18 to 30 years when they completed a baseline clinic examination from 1985 to 1986. Subsequent examinations were conducted 2, 5, 7, 10, 15, and 20 years later. After multivariable adjustment, no association was observed between average coffee, decaffeinated coffee, or caffeine consumption (years 0 and 7) and presence of CAC (score, >0 Agatston units at year 15 or 20), CAC progression (incident CAC at year 20 or increase in CAC score by >= 20 Agatston units), or high carotid intima-media thickness (>80th percentile, year 20). However, tea consumption displayed a nonsignificant trend for an inverse association with CAC (P = 0.08 for trend) and an inverse association with CAC progression (P = 0.04 for trend) but no association with high carotid intima-media thickness (P > 0.20 for trend). Stratification of the coffee analyses by sex, race, or smoking yielded similar nonsignificant patterns. Conclusion-We observed no substantial association between coffee or caffeine intake and coronary and carotid atherosclerosis. However, our results suggested an inverse association between tea and CAC but not carotid atherosclerosis. (Arterioscler Thromb Vasc Biol. 2010; 30: 2059-2066.) C1 [Reis, Jared P.; Loria, Catherine M.] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA. [Steffen, Lyn M.; Zhou, Xia; Jacobs, David R., Jr.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [van Horn, Linda] Feinberg Sch Med, Dept Prevent Med, Chicago, IL USA. [Siscovick, David S.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA. [Siscovick, David S.] Univ Washington, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA USA. [Jacobs, David R., Jr.] Univ Oslo, Dept Nutr, Oslo, Norway. [Carr, J. Jeffrey] Wake Forest Univ, Dept Radiol, Sch Med, Winston Salem, NC 27109 USA. RP Reis, JP (reprint author), NHLBI, Div Cardiovasc Sci, 6701 Rockledge Dr,Ste 10197, Bethesda, MD 20892 USA. EM reisjp@mail.nih.gov RI Carr, John/A-1938-2012 OI Carr, John/0000-0002-4398-8237 FU University of Alabama at Birmingham [N01-HC95095, N01-HC48047]; Kaiser Foundation Research Institute [N01-HC48050]; Northwestern University [N01-HC48049]; University of Minnesota [N01-HC48048] FX The CARDIA Study is conducted and supported by the National Heart, Lung, and Blood Institute in collaboration with the University of Alabama at Birmingham (N01-HC95095 and N01-HC48047), the Kaiser Foundation Research Institute (N01-HC48050), Northwestern University (N01-HC48049), and the University of Minnesota (N01-HC48048). NR 53 TC 18 Z9 20 U1 1 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD OCT PY 2010 VL 30 IS 10 BP 2059 EP 2066 DI 10.1161/ATVBAHA.110.208280 PG 8 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 650VV UT WOS:000281882800028 PM 20616310 ER PT J AU Kang, JG Sung, HJ Jawed, SI Brenneman, CL Rao, YN Sher, S Facio, FM Biesecker, LG Quyyumi, AA Sachdev, V Hwang, PM AF Kang, Ju-Gyeong Sung, Ho Joong Jawed, Sarah I. Brenneman, Cynthia L. Rao, Yesoda N. Sher, Salman Facio, Flavia M. Biesecker, Leslie G. Quyyumi, Arshed A. Sachdev, Vandana Hwang, Paul M. TI FOS expression in blood as a LDL-independent marker of statin treatment SO ATHEROSCLEROSIS LA English DT Article DE FOS; Atherosclerosis; Statin; Inflammation; Pleiotropic; Gene expression; Monocyte; Macrophage; Blood; Biomarker ID CORONARY-ARTERY-DISEASE; C-FOS; ATHEROSCLEROSIS; MECHANISMS AB Objectives: The expression of FOS, a gene critical for monocyte and macrophage function, can be inhibited by statins through the disruption of a cholesterol-independent signaling pathway. In this pilot study, we hypothesized that blood FOS mRNA levels will be sensitive to statin treatment independent of LDL cholesterol levels. Methods: Three cohorts at increased risk of or with cardiovascular disease (CVD) were studied. Blood FOS mRNA levels were measured before and after statin treatment or in patients under stable treatment. Results: Statin treatment for three months significantly reduced blood FOS mRNA and LDL cholesterol levels. However, in subjects with similar LDL levels achieved by different doses of long term statin treatment, there was an inverse relationship between statin dose and FOS expression. Conclusions: FOS mRNA levels appear to be a sensitive marker of statin treatment that is dissociated from cholesterol levels. Published by Elsevier Ireland Ltd. C1 [Hwang, Paul M.] NHLBI, Translat Med Branch, Cardiol Sect, NIH, Bethesda, MD 20892 USA. [Facio, Flavia M.; Biesecker, Leslie G.] NHGRI, NIH, Bethesda, MD 20892 USA. [Sher, Salman; Quyyumi, Arshed A.] Emory Univ, Sch Med, Dept Med, Atlanta, GA USA. RP Hwang, PM (reprint author), NHLBI, Translat Med Branch, Cardiol Sect, NIH, Bldg 10-CRC,Rm 5-5330, Bethesda, MD 20892 USA. EM hwangp@mail.nih.gov RI Library, Woodruff Health/A-6096-2012 FU Pfizer; NHLBI; NHGRI; NIH; National Center for Research Resources (NCRR) [M01-RR00039] FX Dr. Quyyumi has received research funding from Pfizer, which manufactures atorvastatin, a product related to the research described in this paper and has received honoraria as a consultant. The terms of this arrangement have been reviewed and approved by Emory University in accordance with its conflict of interest policies.; The authors wish to thank Drs. Ping-yuan Wang, Myron A. Waclawiw, Michael Sack and Toren Finkel for helpful discussions. We also thank Amy Linn, Danielle Singer, Paul Gobourne and Laurel Mendelsohn and Dr. George Csako for sample and data collection. This research was supported by the Intramural Research Program of the NHLBI and NHGRI, NIH, and the National Center for Research Resources (NCRR) Grant M01-RR00039 for the Emory General Clinical Research Center (GCRC). NR 15 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD OCT PY 2010 VL 212 IS 2 BP 567 EP 570 DI 10.1016/j.atherosclerosis.2010.06.023 PG 4 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 660WZ UT WOS:000282678500036 PM 20619839 ER PT J AU Cerbulo-Vazquez, A Zavala, M Perez-Palacios, GA Jenkins, SL Giavedoni, LD Hodara, VL Romero, R Wimmer, RD Irles, C Nathanielsz, PW AF Cerbulo-Vazquez, A. Zavala, M. Perez-Palacios, G. A. Jenkins, S. L. Giavedoni, Luis D. Hodara, Vida L. Romero, R. Wimmer, Ralf D. Irles, Claudine Nathanielsz, Peter W. TI Baboon fetal arterial endothelial cells are more responsive to challenge by tumor necrosis factor alpha (TNF-alpha) than baboon fetal umbilical vein endothelial cells SO ATHEROSCLEROSIS LA English DT Letter ID MATERNAL HYPERCHOLESTEROLEMIA; EXPRESSION; GENE C1 [Cerbulo-Vazquez, A.; Zavala, M.; Jenkins, S. L.; Wimmer, Ralf D.; Nathanielsz, Peter W.] Univ Texas Hlth Sci Ctr San Antonio, Ctr Pregnancy & Newborn Res, San Antonio, TX 78229 USA. [Cerbulo-Vazquez, A.; Wimmer, Ralf D.] SSA, Inst Nacl Perinatol, Dept Biol Celular, Mexico City 11000, DF, Mexico. [Giavedoni, Luis D.; Hodara, Vida L.; Wimmer, Ralf D.] SW Fdn Biomed Res, Dept Immunol, San Antonio, TX 78227 USA. [Giavedoni, Luis D.; Hodara, Vida L.; Wimmer, Ralf D.] SW Fdn Biomed Res, Immunol Core Lab, Dept Virol & Immunol, SW Natl Primate Res Ctr, San Antonio, TX 78227 USA. [Wimmer, Ralf D.; Irles, Claudine] SSA, Inst Nacl Perinatol, Dept Bioquim & Biol Mol, Mexico City 11000, DF, Mexico. [Romero, R.; Wimmer, Ralf D.] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. [Romero, R.; Wimmer, Ralf D.] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA. [Romero, R.; Wimmer, Ralf D.] Wayne State Univ, Dept Obstet & Gynecol, Hutzel Hosp, Detroit, MI USA. [Romero, R.; Wimmer, Ralf D.] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA. RP Nathanielsz, PW (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Ctr Pregnancy & Newborn Res, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM nathanielsz@uthscsa.edu OI Nathanielsz, Peter/0000-0001-8410-6280 FU Intramural NIH HHS [Z01 HD002400-17]; NICHD NIH HHS [HD 21350-17, P01 HD021350, P01 HD021350-19] NR 15 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD OCT PY 2010 VL 212 IS 2 BP 701 EP 703 DI 10.1016/j.atherosclerosis.2010.06.030 PG 3 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 660WZ UT WOS:000282678500059 PM 20638065 ER PT J AU Shi, CS Kehrl, JH AF Shi, Chong-Shan Kehrl, John H. TI Traf6 and A20 differentially regulate TLR4-induced autophagy by affecting the ubiquitination of Beclin 1 SO AUTOPHAGY LA English DT Editorial Material DE autophagy; toll-like receptor; ubiquirin; Beclin 1; A20; TRAF6 AB Toll-like receptor 4 (TLR4) signaling triggers autophagy, which has been linked to both adaptive and innate immunity. Engagement of TLR4 recruits to the receptor complex Beclin 1, a key component of a class III phosphatidylinositol 3-kinase complex (PI3KC3) that initiates autophagosome formation. Recently, we found that tumor necrosis factor receptor (TNFR)-associated factor 6 (TRAF6)-mediates Lys(63) (K63)-linked ubiquitination of Beclin 1 is crucial for TLR4-triggered autophagy in macrophages. We identified two TRAF6-binding motifs in Beclin 1 that facilitate the binding of TRAF6 and the ubiquitination of Beclin 1. A lysine located in the Bcl-2 homology 3 (BH3) domain of Beclin 1 serves as a major site for K63-linked ubiquitination. Opposing TRAF6, the deubiquitinating enzyme A20 reduces the extent of K63-linked ubiquitination of Beclin 1 and limits the induction of autophagy in response to TLR4 signaling. Furthermore, treatment of macrophages with either interferon gamma or interleukin-1 triggers the K63-linked ubiquitination of Beclin 1 and the formation of autophagosomes. These results indicate that the status of K63-linked ubiquitination of Beclin 1 plays a key role in regulating autophagy during inflammatory responses. C1 [Shi, Chong-Shan; Kehrl, John H.] NIAID, B Cell Mol Immunol Sect, Lab lmmunoregulat, NIH, Bethesda, MD 20892 USA. RP Kehrl, JH (reprint author), NIAID, B Cell Mol Immunol Sect, Lab lmmunoregulat, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM jkehrl@niaid.nih.gov OI Kehrl, John/0000-0002-6526-159X FU Intramural NIH HHS NR 0 TC 29 Z9 31 U1 0 U2 5 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1554-8627 J9 AUTOPHAGY JI Autophagy PD OCT 1 PY 2010 VL 6 IS 7 BP 986 EP 987 DI 10.4161/auto.6.7.13288 PG 2 WC Cell Biology SC Cell Biology GA 661ED UT WOS:000282705400028 PM 20798608 ER PT J AU Macbeth, AH Stepp, JE Lee, HJ Young, WS Caldwell, HK AF Macbeth, Abbe H. Stepp, Jennifer E. Lee, Heon-Jin Young, W. Scott, III Caldwell, Heather K. TI Normal Maternal Behavior, but Increased Pup Mortality, in Conditional Oxytocin Receptor Knockout Females SO BEHAVIORAL NEUROSCIENCE LA English DT Article DE conditional knockout; stress; maternal behavior; aggression ID VASOPRESSIN IMMUNOREACTIVITY; ARGININE-VASOPRESSIN; AGGRESSIVE-BEHAVIOR; GENE-EXPRESSION; LACTATING RATS; MILK EJECTION; FEAR BEHAVIOR; PRAIRIE VOLES; HOUSE MICE; BRAIN AB Oxytocin (Oxt) and the Oxt receptor (Oxtr) are implicated in the onset of maternal behavior in a variety of species. Recently, we developed two Oxtr knockout lines: a total body knockout (Oxtr(-/-)) and a conditional Oxtr knockout (Oxtr(FB/FR)) in which the Oxtr is lacking only in regions of the forebrain, allowing knockout females to potentially nurse and care for their biological offspring. In the current study, we assessed maternal behavior of postpartum Oxtr(FB/FB) females toward their own pups and maternal behavior of virgin Oxtr(-/-) females toward foster pups and compared knockouts of both lines to wildtype (Oxtr(+/+)) littermates. We found that both Oxtr(-/-) and Oxtr(FB/FB) females appear to have largely normal maternal behaviors. However, with first litters, approximately 40% of the Oxtr(FB/FB) knockout dams experienced high pup mortality, compared to fewer than 10% of the Oxtr(+/+) dams. We then went on to test whether or not this phenotype occurred in subsequent litters or when the dams were exposed to an environmental disturbance. We found that regardless of the degree of external disturbance, Oxtr(FB/FB) females lost more pups on their first and second litters compared to wildtype females. Possible reasons for higher pup mortality in Oxtr(FB/FB) females are discussed. C1 [Macbeth, Abbe H.; Stepp, Jennifer E.; Young, W. Scott, III] NIMH, Sect Neural Gene Express 3, NIH, Bethesda, MD 20892 USA. [Lee, Heon-Jin] Kyungpook Natl Univ, Sch Dent, Taegu, South Korea. [Caldwell, Heather K.] Kent State Univ, Neuroendocrinol & Behav Lab, Dept Biol Sci, Kent, OH USA. [Caldwell, Heather K.] Kent State Univ, Sch Biomed Sci, Kent, OH USA. RP Young, WS (reprint author), 9000 Rockville Pike,Bldg 49,Room 5A51, Bethesda, MD 20892 USA. EM wsy@mail.nih.gov RI Young, W Scott/A-9333-2009; OI Young, W Scott/0000-0001-6614-5112; , Heon-Jin/0000-0002-1911-5014 FU NIMH [Z01-MH-002498-21] FX We thank James Heath for technical assistance and Selen Tolu and Anna Brownstein for assistance with behavioral testing and scoring. This research was supported in part by the NIMH Intramural Research Program (Z01-MH-002498-21). NR 65 TC 30 Z9 32 U1 2 U2 11 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0735-7044 J9 BEHAV NEUROSCI JI Behav. Neurosci. PD OCT PY 2010 VL 124 IS 5 BP 677 EP 685 DI 10.1037/a0020799 PG 9 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 660VE UT WOS:000282673800011 PM 20939667 ER PT J AU Kim, P Leckman, JF Mayes, LC Feldman, R Wang, X Swain, JE AF Kim, Pilyoung Leckman, James F. Mayes, Linda C. Feldman, Ruth Wang, Xin Swain, James E. TI The Plasticity of Human Maternal Brain: Longitudinal Changes in Brain Anatomy During the Early Postpartum Period SO BEHAVIORAL NEUROSCIENCE LA English DT Article DE maternal brain; maternal behavior; postpartum; brain structure; neuroimaging ID STRUCTURAL-CHANGES; MORPHOMETRIC MRI; NEURAL SUBSTRATE; BEHAVIOR; RAT; STRESS; ATTACHMENT; EXPERIENCE; DEPRESSION; PHYSIOLOGY AB Animal studies suggest that structural changes occur in the maternal brain during the early postpartum period in regions such as the hypothalamus, amygdala, parietal lobe, and prefrontal cortex and such changes are related to the expression of maternal behaviors. In an attempt to explore this in humans, we conducted a prospective longitudinal study to examine gray matter changes using voxel-based morphometry on high resolution magnetic resonance images of mothers' brains at two time points: 2-4 weeks postpartum and 3-4 months postpartum. Comparing gray matter volumes across these two time points, we found increases in gray matter volume of the prefrontal cortex, parietal lobes, and midbrain areas. Increased gray matter volume in the midbrain including the hypothalamus, substantia nigra. and amygdala was associated with maternal positive perception of her baby. These results suggest that the first months of motherhood in humans are accompanied by structural changes in brain regions implicated in maternal motivation and behaviors. C1 [Kim, Pilyoung] Cornell Univ, Dept Human Dev, Ithaca, NY 14853 USA. [Kim, Pilyoung; Leckman, James F.; Mayes, Linda C.; Feldman, Ruth; Swain, James E.] Yale Univ Sch Med, Child Study Ctr, Program Risk Resilience & Recovery, New Haven, CT USA. [Feldman, Ruth] Bar Ilan Univ, Leslie & Susan Gonda Brain Sci Ctr, IL-52100 Ramat Gan, Israel. [Wang, Xin; Swain, James E.] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA. RP Kim, P (reprint author), NIMH, NIH, 9000 Rockville Pike,Bldg 15K,Rm 208, Bethesda, MD 20892 USA. EM pilyoung.kim@nih.gov RI Swain, James/F-7270-2013 OI Swain, James/0000-0001-8440-0658 FU College of Human Ecology Graduate Research Grant, Cornell University; US-Israel binational science foundation; Institute for the Study of Unlimited Love; National Alliance for Research on Schizophrenia and Depression; National Institute of Mental Health [K05MH076273]; National Institute of Drug Abuse [5K05DA020091]; Associates of the Yale Child Study Center FX This work was supported by College of Human Ecology Graduate Research Grant, Cornell University (PK); the US-Israel binational science foundation (2005-273, RF, JFL), the Institute for the Study of Unlimited Love (JES, JFL): the National Alliance for Research on Schizophrenia and Depression (RE JES), the National Institute of Mental Health (JFL: K05MH076273), the National Institute of Drug Abuse (LCM: 5K05DA020091), and the Associates of the Yale Child Study Center. We thank Dr. Gary W. Evans. Dr. Cindy Hazan, and Dr. Richard Depue for their helpful comments. NR 48 TC 94 Z9 97 U1 2 U2 27 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0735-7044 J9 BEHAV NEUROSCI JI Behav. Neurosci. PD OCT PY 2010 VL 124 IS 5 BP 695 EP 700 DI 10.1037/a0020884 PG 6 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 660VE UT WOS:000282673800013 PM 20939669 ER PT J AU Liu, Y Kawai, K Khashabi, S Deng, CX Liu, YH Yiu, S AF Liu, Ying Kawai, Kirio Khashabi, Shabnam Deng, Chuxia Liu, Yi-Hsin Yiu, Samuel TI Inactivation of Smad4 leads to impaired ocular development and cataract formation SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Smad4; Ocular development; Lens; Eyelid closure failure ID EYELID CLOSURE; LENS INDUCTION; NULL MUTATION; OPTIC FISSURE; MOUSE EMBRYO; MICE; DEFECTS; BMP7; DIFFERENTIATION; EXPRESSION AB Purpose: Signaling by members of the TGF beta superfamily of molecules is essential for embryonic development and homeostasis. Smad4, a key intracellular mediator in TGF beta signaling, forms transcriptional activator complexes with Activin-, BMP-, and TGF beta-restricted Smad proteins. However, the functional role of Smad4 in controlling different visual system compartments has not been fully investigated. Methods: Using the Pax6 promoter-driven Cre transgenic, smad4 was conditionally inactivated in the lens, cornea and ectoderm of the eyelids. Standard histological and molecular analytical approaches were employed to reveal morphological and cellular changes. Results: Inactivation of Smad4 in the lens led to microphthalmia and cataract formation in addition to the persistent adhesion of the retina to the lens and the iris to the cornea. Inactivation of Smad4 from the ectoderm of the eyelid and cornea caused disruption to eyelid fusion and proper development of the corneal epithelium and corneal stroma. Conclusions: Smad4 is required for the development and maintenance of the lens in addition to the proper development of the cornea, eyelids, and retina. (C) 2010 Elsevier Inc. All rights reserved. C1 [Liu, Ying; Kawai, Kirio; Khashabi, Shabnam; Liu, Yi-Hsin; Yiu, Samuel] Univ So Calif, Keck Sch Med, Dept Ophthalmol, Los Angeles, CA 90033 USA. [Liu, Ying; Kawai, Kirio; Khashabi, Shabnam; Liu, Yi-Hsin; Yiu, Samuel] Univ So Calif, Keck Sch Med, Doheny Eye Inst, Los Angeles, CA 90033 USA. [Liu, Ying] Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, State Key Ophthalm Lab, Guangzhou 510060, Guangdong, Peoples R China. [Deng, Chuxia] NIDDK, Biochem & Metab Lab, NIH, Bethesda, MD 20892 USA. RP Liu, Y (reprint author), Univ So Calif, Keck Sch Med, Dept Ophthalmol, Los Angeles, CA 90033 USA. EM yingliu@doheny.org RI deng, chuxia/N-6713-2016 FU China Scholarship Council FX We wish to thank Dr. Peter Gruss and Dr. David Beebe for supplying us with the Le-Cre transgenic animal, Dr. Xun Xu and Dr. Yang Chai for providing us with the initial breeding pairs of foxed Smad4 animals, and Dr. Samuel Zigler for his supply of anti-crystallin antibodies. Dr.Ying Liu is supported by a grant from the China Scholarship Council. NR 28 TC 6 Z9 8 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD OCT 1 PY 2010 VL 400 IS 4 BP 476 EP 482 DI 10.1016/j.bbrc.2010.08.065 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 662YP UT WOS:000282850500005 PM 20735985 ER PT J AU Bargo, S Raafat, A McCurdy, D Amirjazil, I Shu, YM Traicoff, J Plant, J Vonderhaar, BK Callahan, R AF Bargo, Sharon Raafat, Ahmed McCurdy, David Amirjazil, Idean Shu, Youmin Traicoff, June Plant, Joshua Vonderhaar, Barbara K. Callahan, Robert TI Transforming acidic coiled-coil protein-3 (Tacc3) acts as a negative regulator of Notch signaling through binding to CDC10/Ankyrin repeats SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Taac3; Notch; CDC10/Ankyrin repeats; Protein-protein interaction; Yeast two-hybrid ID MAMMARY EPITHELIAL-CELLS; HISTONE ACETYLTRANSFERASES; GENE FAMILY; INTRACELLULAR REGION; ACTIVATED NOTCH4; EXPRESSION; TUMORIGENESIS; MEMBER; MORPHOGENESIS; LOCALIZATION AB We have identified the transforming acidic coiled-coil protein-3 (Tacc3) as a binding partner for Notch4/Int3 and were able to show that it binds to the intracellular domain (ICD) of all members of the Notch receptor family. Members of the Tacc family reside at the centrosomes and associates with microtubules. Recent studies suggest that Tacc3 also contributes to the regulation of gene transcription. Tacc3 specifically interacts with the Notch4/Int3 CDC10/Ankyrin repeats and to a lesser extent, with residues C-terminal to these repeats in the ICD. Dual label immunofluorescence of mouse mammary tissue shows Tacc3 co-localizes with the Notch3 ICD. Co-immunoprecipitation of endogenous Notch and Tacc3 proteins from NIH3T3 cell extracts, lung and mammary gland confirms that these two proteins interact under physiological conditions. In addition, knock down of Tacc3 in NIH3T3 cells leads to the up-regulation of Hey2, a target gene for Notch signaling. The affinity of Tacc3 binding to Notch4/Int3 ICD is similar to that between Rbpj and Notch4/Int3 ICD. Notch4/Int3 ICD-Tacc3 interaction results in the inhibition of transcription from a Hes1-Luciferase reporter vector in COS-1 cells. The inhibition was reversed in these cells by increasing the levels of Rbpj. Taken together, these results suggest that Tacc3 is a negative regulator of the Notch signaling pathway. Published by Elsevier Inc. C1 [Callahan, Robert] NCI, Mammary Biol & Tumorigenesis Lab, NIH, Bethesda, MD 20892 USA. RP Callahan, R (reprint author), NCI, Mammary Biol & Tumorigenesis Lab, NIH, 37 Convent Dr,Bldg 37,Rm 1118, Bethesda, MD 20892 USA. EM rc54d@nih.gov FU NIH, National Cancer Institute, Center for Cancer Research FX We are indebted to K.T. Jeang (NIAID, NIH) for the TAXI, TAT1, and TAT2 expression vectors, and Dr. Ryoichiro Kageyama (Kyoto University) for the Hes1-Luciferase vector. This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 28 TC 10 Z9 10 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 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD OCT 1 PY 2010 VL 400 IS 4 BP 606 EP 612 DI 10.1016/j.bbrc.2010.08.111 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 662YP UT WOS:000282850500027 PM 20804727 ER PT J AU Li, F Patterson, AD Hofer, CC Krausz, KW Gonzalez, FJ Idle, JR AF Li, Fei Patterson, Andrew D. Hoefer, Constance C. Krausz, Kristopher W. Gonzalez, Frank J. Idle, Jeffrey R. TI Comparative metabolism of cyclophosphamide and ifosfamide in the mouse using UPLC-ESI-QT0FMS-based metabolomics SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE Ifosfamide; Cyclophosphamide; Metabolomics; Ultra-performance liquid chromatography; Time-of-flight mass spectrometry; Tandem mass spectrometry ID CHROMATOGRAPHY-PHOTOGRAPHY-DENSITOMETRY; BIOLOGICALLY-ACTIVE METABOLITE; CONTINUOUS-INFUSION; MASS-SPECTROMETRY; METHYLENE-BLUE; PHOSPHORAMIDE MUSTARD; URINARY METABOLITES; MAGNETIC-RESONANCE; CANCER-PATIENTS; IDENTIFICATION AB Ifosfamide (IF) and cyclophosphamide (CP) are common chemotherapeutic agents. Interestingly, while the two drugs are isomers, only IF treatment is known to cause nephrotoxicity and neurotoxicity. Therefore, it was anticipated that a comparison of IF and CP drug metabolites in the mouse would reveal reasons for this selective toxicity. Drug metabolites were profiled by ultra-performance liquid chromatography-linked electrospray ionization quadrupole time-of-flight mass spectrometry (UPLC-ESI-QTOFMS), and the results analyzed by multivariate data analysis. Of the total 23 drug metabolites identified by UPLC-ESI-QTOFMS for both IF and CP, five were found to be novel. Ifosfamide preferentially underwent N-dechloroethylation, the pathway yielding 2-chloroacetaldehyde, while cyclophosphamide preferentially underwent ring-opening, the pathway yielding acrolein (AC). Additionally, S-carboxymethylcysteine and thiodiglycolic acid, two downstream IF and CP metabolites, were produced similarly in both IF- and CP-treated mice. This may suggest that other metabolites, perhaps precursors of thiodiglycolic acid, may be responsible for IF encephalopathy and nephropathy. (C) 2010 Elsevier Inc. All rights reserved. C1 [Idle, Jeffrey R.] Charles Univ Prague, Inst Pharmacol, Fac Med 1, Prague 12800 2, Czech Republic. [Li, Fei; Patterson, Andrew D.; Krausz, Kristopher W.; Gonzalez, Frank J.; Idle, Jeffrey R.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20852 USA. [Hoefer, Constance C.] DMPKORE, D-85057 Ingolstadt, Germany. RP Idle, JR (reprint author), Charles Univ Prague, Inst Pharmacol, Fac Med 1, Albertov 4, Prague 12800 2, Czech Republic. EM lif3@mail.nih.gov; andrewpatterson@mail.nih.gov; c.hoefer@dmpkore.com; krauszk@intra.nci.nih.gov; fjgonz@helix.nih.gov; idlejr@mail.nih.gov RI Patterson, Andrew/G-3852-2012; Li, Fei/F-6849-2013 OI Patterson, Andrew/0000-0003-2073-0070; FU Center for Cancer Research, National Cancer Institute, National Institutes of Health; U.S. Smokeless Tobacco Company FX This work was supported in part by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health. JRI is grateful to the U.S. Smokeless Tobacco Company for a grant for collaborative research. The authors thank Professor Adrian Kupfer, University of Bern, for helpful discussions. NR 67 TC 31 Z9 34 U1 1 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD OCT 1 PY 2010 VL 80 IS 7 BP 1063 EP 1074 DI 10.1016/j.bcp.2010.06.002 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 645CP UT WOS:000281428800014 PM 20541539 ER PT J AU Preabrazhenskaya, YV Kim, IY Stadtman, TC AF Preabrazhenskaya, Y. V. Kim, I. Y. Stadtman, T. C. TI Binding of ATP and Its Derivatives to Selenophosphate Synthetase from Escherichia coli (Retraction of vol 74, pg 910, 2009) SO BIOCHEMISTRY-MOSCOW LA English DT Correction C1 [Preabrazhenskaya, Y. V.; Kim, I. Y.; Stadtman, T. C.] NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. [Preabrazhenskaya, Y. V.] Grodno State Univ, Dept Biol & Ecol, Grodno 230015, Byelarus. RP Preabrazhenskaya, YV (reprint author), NHLBI, Biochem Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM yuliya.preabrazh@gmail.com NR 1 TC 0 Z9 0 U1 1 U2 8 PU MAIK NAUKA/INTERPERIODICA/SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013-1578 USA SN 0006-2979 J9 BIOCHEMISTRY-MOSCOW+ JI Biochem.-Moscow PD OCT PY 2010 VL 75 IS 10 BP 1302 EP 1302 DI 10.1134/S0006297910100135 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 672BO UT WOS:000283558200013 ER PT J AU McCann, TE Kosaka, N Mitsunaga, M Choyke, PL Gildersleeve, JC Kobayashi, H AF McCann, Thomas E. Kosaka, Nobuyuki Mitsunaga, Makoto Choyke, Peter L. Gildersleeve, Jeffrey C. Kobayashi, Hisataka TI Biodistribution and Excretion of Monosaccharide-Albumin Conjugates Measured with in Vivo Near-Infrared Fluorescence Imaging SO BIOCONJUGATE CHEMISTRY LA English DT Article ID FUCOSE-CONTAINING GLYCOPROTEINS; SERUM-ALBUMIN; HEPATIC LECTINS; BINDING; LIVER; RECEPTORS; ANTIBODY; IN-111; CANCER; I-125 AB Target specific small molecules as modulators of drug delivery may play a significant role in the future development of therapeutics. Small molecules can alter the in vivo pharmacokinetics of therapeutic macromolecules leading to more efficient drug delivery with less systemic toxicity. The potential of creating a more effective drug delivery system through glycosylation has led, for instance, to the addition of galactose to increase drug delivery to the liver. However, there are many other monosaccharides with potentially useful targeting properties that require further characterization. Here, we investigate the potential of glycosylation to guide molecular therapies using five different monosaccharides conjugated to human serum albumin (HSA). Additionally, we investigate how the amount of glycosylation may alter the pharmacokinetic profile of HSA. We introduce the use of in vivo near-infrared optical imaging to characterize the effect of differential glycosylation on the pharmacokinetics of macromolecules. C1 [McCann, Thomas E.; Kosaka, Nobuyuki; Mitsunaga, Makoto; Choyke, Peter L.; Kobayashi, Hisataka] NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Gildersleeve, Jeffrey C.] NCI, Biol Chem Lab, Ctr Canc Res, NIH, Frederick, MD 21702 USA. RP Kobayashi, H (reprint author), NCI, Mol Imaging Program, Ctr Canc Res, NIH, Bldg 10,Room B3B69,MSC1088, Bethesda, MD 20892 USA. EM kobayash@mail.nih.gov RI Gildersleeve, Jeffrey/N-3392-2014 FU NIH, National Cancer Institute, Center for Cancer Research; Pfizer Inc; NIH FX This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. This research year was made possible through the Clinical Research Training Program, a public private partnership supported jointly by the NIH and Pfizer Inc (via a grant to the Foundation for NIH from Pfizer Inc). NR 20 TC 11 Z9 13 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD OCT PY 2010 VL 21 IS 10 BP 1925 EP 1932 DI 10.1021/bc100313p PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 666FZ UT WOS:000283101000027 PM 20853850 ER PT J AU Hurst, S AF Hurst, Samia TI WHAT 'EMPIRICAL TURN IN BIOETHICS'? SO BIOETHICS LA English DT Article DE ethics; empirical research; ethical theory; methodology; interdisciplinary communication ID ETHICS; FUTURE; OUGHT AB Uncertainty as to how we should articulate empirical data and normative reasoning seems to underlie most difficulties regarding the 'empirical turn' in bioethics. This article examines three different ways in which we could understand 'empirical turn'. Using real facts in normative reasoning is trivial and would not represent a 'turn'. Becoming an empirical discipline through a shift to the social and neurosciences would be a turn away from normative thinking, which we should not take. Conducting empirical research to inform normative reasoning is the usual meaning given to the term 'empirical turn'. In this sense, however, the turn is incomplete. Bioethics has imported methodological tools from empirical disciplines, but too often it has not imported the standards to which researchers in these disciplines are held. Integrating empirical and normative approaches also represents true added difficulties. Addressing these issues from the standpoint of debates on the fact-value distinction can cloud very real methodological concerns by displacing the debate to a level of abstraction where they need not be apparent. Ideally, empirical research in bioethics should meet standards for empirical and normative validity similar to those used in the source disciplines for these methods, and articulate these aspects clearly and appropriately. More modestly, criteria to ensure that none of these standards are completely left aside would improve the quality of empirical bioethics research and partly clear the air of critiques addressing its theoretical justification, when its rigour in the particularly difficult context of interdisciplinarity is what should be at stake. C1 [Hurst, Samia] Geneva Sch Med, Inst Biomed Eth, CH-1211 Geneva 4, Switzerland. [Hurst, Samia] Univ Hosp Geneva, Clin Eth Council, Geneva, Switzerland. [Hurst, Samia] NIH, Dept Clin Bioeth, Bethesda, MD USA. RP Hurst, S (reprint author), Geneva Sch Med, Inst Biomed Eth, CMU 1 Rue Michel Servet, CH-1211 Geneva 4, Switzerland. EM samia.hurst@unige.ch RI Hurst, Samia/A-9661-2008 OI Hurst, Samia/0000-0002-1980-5226 FU Institute for Biomedical Ethics at the University of Geneva; Swiss National Science Foundation [3233B0-107266/1] FX The author warmly thanks Alex Mauron PhD and the anonymous reviewers for very insightful and constructive comments, as well as her students. This work was funded by the Institute for Biomedical Ethics at the University of Geneva, and by the Swiss National Science Foundation (grant 3233B0-107266/1). The funding sources were not involved in the study design, in the collection, analysis, and interpretation of data, in the writing of the report or in the decision to submit the paper for publication. NR 34 TC 14 Z9 14 U1 1 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0269-9702 J9 BIOETHICS JI Bioethics PD OCT PY 2010 VL 24 IS 8 BP 439 EP 444 DI 10.1111/j.1467-8519.2009.01720.x PG 6 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 647RH UT WOS:000281635800008 PM 19438442 ER PT J AU Liu, BH Yu, H Tu, K Li, C Li, YX Li, YY AF Liu, Bao-Hong Yu, Hui Tu, Kang Li, Chun Li, Yi-Xue Li, Yuan-Yuan TI DCGL: an R package for identifying differentially coexpressed genes and links from gene expression microarray data SO BIOINFORMATICS LA English DT Article ID CANCER AB Gene coexpression analysis was developed to explore gene interconnection at the expression level from a systems perspective, and differential coexpression analysis (DCEA), which examines the change in gene expression correlation between two conditions, was accordingly designed as a complementary technique to traditional differential expression analysis (DEA). Since there is a shortage of DCEA tools, we implemented in an R package 'DCGL' five DCEA methods for identification of differentially coexpressed genes and differentially coexpressed links, including three currently popular methods and two novel algorithms described in a companion paper. DCGL can serve as an easy-to-use tool to facilitate differential coexpression analyses. C1 [Liu, Bao-Hong; Li, Yi-Xue] Tongji Univ, Sch Life Sci & Technol, Shanghai 200092, Peoples R China. [Liu, Bao-Hong; Yu, Hui; Li, Yi-Xue; Li, Yuan-Yuan] Chinese Acad Sci, Shanghai Inst Biol Sci, Bioinformat Ctr, Key Lab Syst Biol, Shanghai 200031, Peoples R China. [Liu, Bao-Hong; Yu, Hui; Li, Yi-Xue; Li, Yuan-Yuan] Shanghai Ctr Bioinformat Technol, Shanghai 200235, Peoples R China. [Tu, Kang] NHLBI, NIH, Bethesda, MD USA. [Li, Chun] Vanderbilt Univ, Sch Med, Dept Biostat, Ctr Human Genet Res, Nashville, TN 37232 USA. RP Li, YX (reprint author), Tongji Univ, Sch Life Sci & Technol, Shanghai 200092, Peoples R China. EM yxli@scbit.org; yyli@scbit.org RI Li, Chun/B-8388-2012 FU Shanghai Institutes for Biological Sciences; Chinese Academy of Sciences [2008KIP207]; National '973' Basic Research Program [2006CB0D1203, 2006CB0D1205]; National Natural Science Foundation of China [30770497, 31000380]; National Key Technologies RD Program [2007AA02Z331, 2009ZX10603] FX Shanghai Institutes for Biological Sciences; Chinese Academy of Sciences (2008KIP207); the National '973' Basic Research Program (2006CB0D1203, 2006CB0D1205); the National Natural Science Foundation of China (30770497, 31000380); National Key Technologies R&D Program (2007AA02Z331 and 2009ZX10603). NR 4 TC 43 Z9 44 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD OCT PY 2010 VL 26 IS 20 BP 2637 EP 2638 DI 10.1093/bioinformatics/btq471 PG 2 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 661SZ UT WOS:000282749700026 PM 20801914 ER PT J AU Tarabeux, J Champagne, N Brustein, E Hamdan, FF Gauthier, J Lapointe, M Maios, C Piton, A Spiegelman, D Henrion, E Millet, B Rapoport, JL DeLisi, LE Joober, R Fathalli, F Fombonne, E Mottron, L Forget-Dubois, N Boivin, M Michaud, JL Lafreniere, RG Drapeau, P Krebs, MO Rouleau, GA AF Tarabeux, Julien Champagne, Nathalie Brustein, Edna Hamdan, Fadi F. Gauthier, Julie Lapointe, Mathieu Maios, Claudia Piton, Amelie Spiegelman, Dan Henrion, Edouard Millet, Bruno Rapoport, Judith L. DeLisi, Lynn E. Joober, Ridha Fathalli, Fend Fombonne, Eric Mottron, Laurent Forget-Dubois, Nadine Boivin, Michel Michaud, Jacques L. Lafreniere, Ronald G. Drapeau, Pierre Krebs, Marie-Odile Rouleau, Guy A. CA Synapse Dis Team TI De Novo Truncating Mutation in Kinesin 17 Associated with Schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Article DE De novo; KIF17; kinesin; NMDA; schizophrenia; synapse ID FAMILY-BASED ASSOCIATION; MOTOR PROTEIN KIF17; SYNAPTIC PLASTICITY; NEUROPSYCHIATRIC DISORDERS; SUBUNIT COMPOSITION; MESSENGER-RNA; GENE; RECEPTORS; IDENTIFICATION; EXPRESSION AB Background: Schizophrenia (SCZ) is one of the most disabling psychiatric disorders. It is thought to be due to a complex interplay between polygenic and various environmental risk factors, although recent reports on genomic copy number variations suggest that a fraction of the cases could result from variably penetrant de novo variants. The gene encoding the synaptic motor protein kinesin 17 (KIF17) involved in glutamatergic synapse is a candidate gene for SCZ. Methods: As part of our Synapse to Disease project, we resequenced KIF17 in a cohort of individuals with sporadic SCZ (188 subjects). Additional populations included autism spectrum disorder (142 subjects), nonsyndromic mental retardation (95 subjects), and control subjects (568 subjects). Functional validation of the human mutation was done in developing zebrafish. Results: Here we report the identification of a de novo nonsense truncating mutation in one patient with SCZ, in kinesin 17, a synaptic motor protein. No de novo or truncating KIF17 mutations were found in the additional samples. We further validated the pathogenic nature of this mutation by knocking down its expression in zebrafish embryos, which resulted in a developmental defect. Conclusions: Together our findings suggest that disruption of KIF17, although rare, could result in a schizophrenia phenotype and emphasize the possible involvement of rare de novo mutations in this disorder. C1 [Rouleau, Guy A.] Univ Montreal, CHUM Res Ctr, Ctr Excellence Neur, Montreal, PQ H2L 2W5, Canada. [Tarabeux, Julien; Gauthier, Julie; Spiegelman, Dan; Henrion, Edouard; Lafreniere, Ronald G.; Rouleau, Guy A.] Univ Montreal, Dept Med, Montreal, PQ H2L 2W5, Canada. [Tarabeux, Julien; Millet, Bruno; Krebs, Marie-Odile] INSERM, Lab Pathophysiol Psychiat Dis, Ctr Psychiat & Neurosci, F-75654 Paris, France. [Tarabeux, Julien; Millet, Bruno; Krebs, Marie-Odile] Univ Paris 05, Ctr Evaluat & Rech Clin, Hop St Anne, Paris, France. [Champagne, Nathalie; Brustein, Edna; Lapointe, Mathieu; Maios, Claudia; Drapeau, Pierre] Univ Montreal, Dept Pathol & Cell Biol, Montreal, PQ H2L 2W5, Canada. [Champagne, Nathalie; Brustein, Edna; Lapointe, Mathieu; Maios, Claudia; Drapeau, Pierre; Synapse Dis Team] Univ Montreal, Le Grp Rech Syst Nerveux Cent, Montreal, PQ H2L 2W5, Canada. Univ Montreal, Res Ctr, Ctr Hosp Univ St Justine, Montreal, PQ H2L 2W5, Canada. [Hamdan, Fadi F.; Michaud, Jacques L.] Univ Montreal, Dept Med Genet, Montreal, PQ H2L 2W5, Canada. Ctr Hosp Guillaume Regnier, Serv Hosp Univ Psychiat, Rennes, France. [Rapoport, Judith L.] NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. [DeLisi, Lynn E.] Harvard Univ, Sch Med, Boston Vet Affairs Healthcare Syst, Brockton, MA 02401 USA. [Joober, Ridha; Fathalli, Fend] McGill Univ, Dept Psychiat, Douglas Mental Hlth Univ Inst, Montreal, PQ, Canada. [Fombonne, Eric] McGill Univ, Montreal Childrens Hosp, Dept Psychiat, Montreal, PQ H3H 1P3, Canada. [Mottron, Laurent] Univ Montreal, Ctr Rech Fernand Seguin, Hop Riviere des Prairies, Montreal, PQ H2L 2W5, Canada. [Forget-Dubois, Nadine; Boivin, Michel] Univ Laval, Canada Res Chair Child Social Dev, Res Unit Childrens Psychosocial Maladjustment, Quebec City, PQ, Canada. RP Rouleau, GA (reprint author), Univ Montreal, CHUM Res Ctr, Ctr Excellence Neur, 2099 Alexandre De Seve St,Rm Y-3633, Montreal, PQ H2L 2W5, Canada. EM guy.rouleau@umontreal.ca RI Boivin, Michel/J-3652-2013; Forget-Dubois, Nadine/A-4811-2013; OI Forget-Dubois, Nadine/0000-0002-4285-3293; Piton, Amelie/0000-0003-0408-7468 FU Genome Canada; Genome Quebec; Universite de Montreal; Canadian Foundation for Innovation; Universite Paris Descartes; Canadian Institutes of Health Research; Fondation Pierre Deniker FX This work was supported by Genome Canada and Genome Quebec and received cofunding from Universite de Montreal for the Synapse to Disease project as well as funding from the Canadian Foundation for Innovation. JT receives a scholarship from the Universite Paris Descartes (joint program Universite Paris Descartes-Universite de Montreal). GAR holds the Canada Research Chair in Genetics of the Nervous System; PD holds the Canada Research Chair in Neuroscience. JLM is a recipient of the Clinical Investigator Award of Canadian Institutes of Health Research. The Synapse to Disease team is composed of the following additional members: Isabelle Bachand, Marjolaine Chicoine Melanie Cote, Kathleen Daignault, Anne Desjarlais, Ousmane Diallo, Sylvia Dobrzeniecka, Joanilie Duguay Marina Dots, Philippe Jolivet, Liliane Karamera, Frederic Kuku, Karine Lachapelle, Guy Laliberte, Sandra Laurent, Annie Levert, Meijiang Liao, Claude Marineau, Carlos Marino, Anne Noreau, Huashan Peng, Annie Raymond, Annie Reynolds, Daniel Rochefort, Judith St-Onge, Pascale Thibodeau, Kazuya Tsurudome, Yan Yang, Sophie Leroy, Katia Ossian Melanie Chayet, and F. Mouaffak.; We thank all the families involved in this study. We also thank Dr. Chawki Benkelfat for several helpful discussions. A portion of the Schizophrenia cohort was collected through the Collaborative Network for Family Study in Psychiatry ("Reseau d'etude familiale en Psychiatry"), supported by the Fondation Pierre Deniker. We also acknowledge the efforts of the members of the Genome Quebec Innovation Centre Sequencing (Pierre Lepage, Sebastien Brunet, and Hao Fan Yam) and Bioinformatic (Louis Letourneau and Louis Dumond Joseph) groups. NR 53 TC 26 Z9 26 U1 6 U2 17 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD OCT 1 PY 2010 VL 68 IS 7 BP 649 EP 656 DI 10.1016/j.biopsych.2010.04.018 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 656SM UT WOS:000282356900010 PM 20646681 ER PT J AU Zhang, XC Stein, EA Hong, LE AF Zhang, Xiaochu Stein, Elliot A. Hong, L. Elliot TI Smoking and Schizophrenia Independently and Additively Reduce White Matter Integrity Between Striatum and Frontal Cortex SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Addiction; diffusion tensor imaging (DTI); fractional anisotropy (FA); nicotine; schizophrenia; white matter ID CIGARETTE-SMOKING; BIPOLAR DISORDER; DIFFUSION; MEMORY; IMPAIRMENTS; COGNITION AB Background: Although schizophrenia patients are at high risk for tobacco use, the neurobiological basis of this comorbid association is not clear. White matter abnormalities have been described independently in schizophrenia and smoking cohorts. We sought to determine whether smoking and schizophrenia are associated with similar white matter abnormalities that could be biomarkers for the high risk of smoking in schizophrenia. Methods: Whole brain white matter integrity (fractional anisotropy) was measured in 46 schizophrenia patients (32 smokers and 14 nonsmokers) and 69 healthy age-matched control subjects (48 smokers and 21 nonsmokers). Results: Schizophrenia and smoking status were independently and additively associated with reduced fractional anisotropy in left anterior thalamic radiation/anterior limb of the internal capsule, and significant fractional anisotropy decreases were identified in the bilateral uncinate fasciculus/inferior fronto-occipital fasciculus in schizophrenia and the left prefrontal area in smoking status separately. Conclusions: Common and distinct patterns of impaired white matter are associated with schizophrenia and smoking. Particularly, the anatomic congruence of an additive white matter abnormality in the anterior thalamic radiation/anterior limb of the internal capsule suggests that this abnormal fiber connectivity between frontal cortex and striatum/thalamus may be a biomarker for the increased comorbid smoking in schizophrenia patients. C1 [Hong, L. Elliot] Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, Dept Psychiat, Baltimore, MD 21228 USA. [Zhang, Xiaochu; Stein, Elliot A.] NIDA, Neuroimaging Res Branch, NIH, Baltimore, MD USA. RP Hong, LE (reprint author), Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, Dept Psychiat, Box 21247, Baltimore, MD 21228 USA. EM ehong@mprc.umaryland.edu RI Zhang, Xiaochu/O-9592-2014 OI Zhang, Xiaochu/0000-0002-7541-0130 FU National Institute on Drug Abuse, National Institute on Health [MH70644, N01-da-5-9909]; Maryland Cigarette Restitution Fund Program Other Tobacco-Related Diseases Research Grant FX This research was supported by the Intramural Research Program of the National Institute on Drug Abuse, National Institute on Health, and Grant Nos. MH70644, N01-da-5-9909, and the Maryland Cigarette Restitution Fund Program Other Tobacco-Related Diseases Research Grant. We thank Brittany Buchholz, Kimberly Modo, and Loretta Spurgeon for their assistance in the conduct of the study. NR 20 TC 22 Z9 23 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD OCT 1 PY 2010 VL 68 IS 7 BP 674 EP 677 DI 10.1016/j.biopsych.2010.06.018 PG 4 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 656SM UT WOS:000282356900014 PM 20678753 ER PT J AU Bufalari, I Sforza, A Cesari, P Aglioti, SM Fourkas, AD AF Bufalari, I. Sforza, A. Cesari, P. Aglioti, S. M. Fourkas, A. D. TI Motor imagery beyond the joint limits: A transcranial magnetic stimulation study SO BIOLOGICAL PSYCHOLOGY LA English DT Article DE Motor imagery; Transcranial magnetic stimulation; Impossible movements; Motor excitability; Metacarpo-phalangeal joint ID IMAGINED HAND MOVEMENTS; EVOKED-POTENTIALS MEPS; CORTICOSPINAL EXCITABILITY; IMPOSSIBLE MOVEMENTS; CORTEX EXCITABILITY; FMRI; FACILITATION; POSTURE; REPRESENTATIONS; MODULATION AB The processes and neural bases used for motor imagery are also used for the actual execution of correspondent movements. Humans, however, can imagine movements they cannot perform. Here we explored whether plausibility of movements is mapped on the corticospinal motor system and whether the process is influenced by visuomotor vs. kinesthetic-motor first person imagery strategy. Healthy subjects imagined performing possible or biomechanically impossible right index finger movements during single pulse TMS of the left motor cortex. We found an increase of corticospinal excitability during motor imagery which was higher for impossible than possible movements and specific for the muscle involved in the actual execution of the imagined movement. We expand our previous action observation studies, suggesting that the plausibility of a movement is computed in regions upstream the primary motor cortex, and that motor imagery is a higher-order process not fully constrained by the rules that govern motor execution. (c) 2010 Elsevier B.V. All rights reserved. C1 [Bufalari, I.; Sforza, A.; Aglioti, S. M.] Univ Roma La Sapienza, Dept Psychol, I-00185 Rome, Italy. [Bufalari, I.; Sforza, A.; Aglioti, S. M.] IRCCS Fdn Santa Lucia, I-00100 Rome, Italy. [Cesari, P.] Univ Verona, Fac Exercise & Sport Sci, I-37131 Verona, Italy. [Fourkas, A. D.] NINDS, Human Cort Physiol Sect, NIH, Bethesda, MD 20892 USA. RP Bufalari, I (reprint author), Univ Roma La Sapienza, Dept Psychol, Via Marsi 78, I-00185 Rome, Italy. EM ilaria.bufalari@gmail.com; salvatoremaria.aglioti@uniroma1.it RI Bufalari, Ilaria/J-5810-2016 OI Bufalari, Ilaria/0000-0001-8675-5436 FU Italian Institute of Technology; Ministero Italian Universita' e Ricerca (MIUR) FX This research was supported by grants from the Project SEED (Italian Institute of Technology) and Ministero Italian Universita' e Ricerca (MIUR) to SMA. Thanks to Michela Romani and Stefano Facchini for their help in a preliminary phase of the study. NR 51 TC 5 Z9 5 U1 0 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-0511 J9 BIOL PSYCHOL JI Biol. Psychol. PD OCT PY 2010 VL 85 IS 2 BP 283 EP 290 DI 10.1016/j.biopsycho.2010.07.015 PG 8 WC Psychology, Biological; Behavioral Sciences; Psychology; Psychology, Experimental SC Psychology; Behavioral Sciences GA 664ZI UT WOS:000283002400013 PM 20688131 ER PT J AU Kroger, N Bacher, U Bader, P Bottcher, S Borowitz, MJ Dreger, P Khouri, I Olavarria, E Radich, J Stock, W Vose, JM Weisdorf, D Willasch, A Giralt, S Bishop, MR Wayne, AS AF Kroeger, Nicolaus Bacher, Ulrike Bader, Peter Boettcher, Sebastian Borowitz, Michael J. Dreger, Peter Khouri, Issa Olavarria, Eduardo Radich, Jerald Stock, Wendy Vose, Julie M. Weisdorf, Daniel Willasch, Andre Giralt, Sergio Bishop, Michael R. Wayne, Alan S. TI NCI First International Workshop on the Biology, Prevention, and Treatment of Relapse after Allogeneic Hematopoietic Stem Cell Transplantation: Report from the Committee on Disease-Specific Methods and Strategies for Monitoring Relapse Following Allogeneic Stem Cell Transplantation. Part II: Chronic Leukemias, Myeloproliferative Neoplasms, and Lymphoid Malignancies SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Allogeneic stem cell transplantation; Minimal residual disease; Chimerism; Chronic leukemias; Myeloproliferative neoplasms; lymphoid malignancies ID CHRONIC LYMPHOCYTIC-LEUKEMIA; CHRONIC MYELOID-LEUKEMIA; MINIMAL RESIDUAL DISEASE; POLYMERASE-CHAIN-REACTION; BONE-MARROW-TRANSPLANTATION; CHRONIC MYELOGENOUS LEUKEMIA; BCR-ABL TRANSCRIPTS; POSITRON-EMISSION-TOMOGRAPHY; GRAFT-VERSUS-LEUKEMIA; ADVANCED MULTIPLE-MYELOMA AB Relapse has become the major cause of treatment failure after allogeneic hematopoietic stem cell transplantation. Outcome of patients with clinical relapse after transplantation generally remains poor, but intervention prior to florid relapse improves outcome for certain hematologic malignancies. To detect early relapse or minimal residual disease, sensitive methods such as molecular genetics, tumor-specific molecular primers, fluorescence in situ hybridization (FISH), and multiparameter flow cytometry (MFC) are commonly used after allogeneic stem cell transplantation to monitor patients, but not all of them are included in the commonly employed disease-specific response criteria. The highest sensitivity and specificity can be achieved by molecular monitoring of tumor- or patient-specific markers measured by polymerase chain reaction-based techniques, but not all diseases have such targets for monitoring. Similar high sensitivity can be achieved by determination of recipient-donor chimerism, but its specificity regarding detection of relapse is low and differs substantially among diseases. Here, we summarize the current knowledge about the utilization of such sensitive monitoring techniques in chronic leukemias, myeloproliferative neoplasms, and lymphoid malignancies based on tumor-specific markers and cell chimerism and how these methods might augment the standard definitions of posttransplant remission, persistence, progression, relapse, and the prediction of relapse. Critically important is the need for standardization of the different residual disease techniques and to assess the clinical relevance of minimal residual disease and chimerism surveillance in individual diseases, which in turn must be followed by studies to assess the potential impact of specific interventional strategies. Biol Blood Marrow Transplant 16: 1325-1346 (2010) (c) 2010 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved. C1 [Bader, Peter; Willasch, Andre] Univ Hosp Frankfurt, Dept Pediat Hematol Oncol, Frankfurt, Germany. [Boettcher, Sebastian] Univ Hosp Schleswig Holstein, Dept Med 2, Kiel, Germany. [Borowitz, Michael J.] Johns Hopkins Univ, Dept Pathol, Baltimore, MD USA. [Dreger, Peter] Univ Heidelberg, Dept Med 5, D-6900 Heidelberg, Germany. [Khouri, Issa; Giralt, Sergio] Univ Texas Houston, MD Anderson Canc Ctr, Div Hematol, Houston, TX 77030 USA. [Olavarria, Eduardo] Hosp Navarra, Serv Hematol, Pamplona, Spain. [Radich, Jerald] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. [Stock, Wendy] Univ Chicago, Chicago, IL 60637 USA. [Kroeger, Nicolaus; Bacher, Ulrike] Univ Med Ctr Hamburg Eppendorf, Dept Stem Cell Transplantat, Hamburg, Germany. [Vose, Julie M.] Univ Nebraska Med Ctr, Omaha, NE USA. [Weisdorf, Daniel] Univ Minnesota, Minneapolis, MN USA. [Bishop, Michael R.] Natl Canc Inst, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD USA. [Wayne, Alan S.] Natl Canc Inst, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD USA. RP Kroger, N (reprint author), Clin Stem Cell Transplantat, Ctr Oncol, Univ Med Ctr, Martinistr 52, D-20246 Hamburg, Germany. EM nkroeger@uke.uni-hamburg.du; waynea@mail.nih.gov NR 157 TC 17 Z9 19 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD OCT PY 2010 VL 16 IS 10 BP 1325 EP 1346 DI 10.1016/j.bbmt.2010.07.001 PG 22 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 653EQ UT WOS:000282071500001 PM 20637879 ER PT J AU Imanguli, MM Atkinson, JC Mitchell, SA Avila, DN Bishop, RJ Cowen, EW Datiles, MB Hakim, FT Kleiner, DE Krumlauf, MC Pavletici, SZ AF Imanguli, Matin M. Atkinson, Jane C. Mitchell, Sandra A. Avila, Daniele N. Bishop, Rachel J. Cowen, Edward W. Datiles, Manuel B. Hakim, Frances T. Kleiner, David E. Krumlauf, Michael C. Pavletici, Steven Z. TI Salivary Gland Involvement in Chronic Graft-Versus-Host Disease: Prevalence, Clinical Significance, and Recommendations for Evaluation SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE CGVHD; Sicca syndrome; Xerostomia; Xerophthalmia; Sjogren's syndrome ID CONSENSUS DEVELOPMENT PROJECT; BONE-MARROW-TRANSPLANTATION; WORKING GROUP-REPORT; STEM-CELL TRANSPLANTATION; TERM FOLLOW-UP; SJOGRENS-SYNDROME; SICCA-SYNDROME; CRITERIA; DIAGNOSIS; PATHOLOGY AB Although xerostomia is a commonly reported complaint in patients with chronic graft-versus-host disease (cGVHD), criteria for evaluating the prevalence and characteristics of salivary gland involvement have not been well defined in this patient population. Previous studies also have made no distinction between salivary and mucosal oral cGVHD. We systematically evaluated signs and symptoms of sicca in a large cohort of patients with cGVHD (n = 101) using instruments widely used to study Sjogren's syndrome. Xerostomia was reported by 77% of the patients and was associated with xerophthalmia in all but I case. The salivary flow rate was <= 0.2 mL/min in 27%, and <= 0.1 mL/min in 16%. Histopathological changes, consisting of mononuclear infiltration and/or fibrosis/atrophy, were present in all patients with salivary dysfunction. Importantly, there was no correlation of salivary and oral mucosal involvement in cGVHD. Patients with cGVHD-associated salivary gland involvement had diminished oral cavity-specific quality of life and lower body mass index. Salivary gland involvement is a common and clinically distinct manifestation of cGVHD. Formal evaluation of salivary function using standardized criteria is needed, and this could be incorporated as an outcome measure in clinical trials of cGVHD. Biol Blood Marrow Transplant 16: 1362-1369 (2010) Published by Elsevier Inc. on behalf of American Society for Blood and Marrow Transplantation C1 [Imanguli, Matin M.; Avila, Daniele N.; Hakim, Frances T.; Krumlauf, Michael C.; Pavletici, Steven Z.] NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Atkinson, Jane C.] Natl Inst Dent & Craniofacial Res, Clin Trials Program, NIH, Bethesda, MD USA. [Mitchell, Sandra A.] Natl Inst Hlth Clin Ctr, NIH, Bethesda, MD USA. [Bishop, Rachel J.; Datiles, Manuel B.] NEI, Consult Sect, Clin Branch, NIH, Bethesda, MD 20892 USA. [Cowen, Edward W.] NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. [Kleiner, David E.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Imanguli, MM (reprint author), NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, NIH, 10 Ctr Dr,12C121, Bethesda, MD 20892 USA. EM mimanguli@mail.nih.gov OI Datiles, Manuel III B./0000-0003-4660-1664; Kleiner, David/0000-0003-3442-4453 FU National Cancer Institute; National Eye Institute; National Institute of Dental and Craniofacial Research FX The authors thank all of the members of the NIH chronic GVHD clinic and study group for their help with data collection, particularly Jeanne Odom, Niveen Atlam, and Bazetta Black lock Schuver. They also thank Dr. Seth Steinberg for critical reading of the manuscript and valuable comments on the statistical methods used in the article. Finally, they are grateful to all the patients who volunteered for this study. This work was supported by the Intramural Research Programs of the National Cancer Institute, the National Eye Institute, and the National Institute of Dental and Craniofacial Research. NR 31 TC 30 Z9 31 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD OCT PY 2010 VL 16 IS 10 BP 1362 EP 1369 DI 10.1016/j.bbmt.2010.03.023 PG 8 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 653EQ UT WOS:000282071500004 PM 20353829 ER PT J AU Sitzmann, BD Leone, EH Mattison, JA Ingram, DK Roth, GS Urbanski, HF Zelinski, MB Ottinger, MA AF Sitzmann, Brandon D. Leone, Erin H. Mattison, Julie A. Ingram, Donald K. Roth, George S. Urbanski, Henryk F. Zelinski, Mary B. Ottinger, Mary Ann TI Effects of Moderate Calorie Restriction on Testosterone Production and Semen Characteristics in Young Rhesus Macaques (Macaca mulatta) SO BIOLOGY OF REPRODUCTION LA English DT Article DE calorie restriction; rhesus macaque; semen collection; sperm; testis; testosterone ID CHROMATIN-STRUCTURE ASSAY; BODY-MASS INDEX; DIETARY RESTRICTION; BONNET MONKEYS; QUALITY; PARAMETERS; IMPACT; SPERMATOZOA; COLLECTION; PRIMATES AB We have previously reported a modest influence of moderate calorie restriction (CR) on testicular gene expression in young adult rhesus macaques (Macaca mulatta); however, it is unclear if these modifications correspond to subsequent changes in testicular function or sperm physiology. This study extends our earlier findings to examine potential physiological differences due to this differential gene expression. Animals were subjected to 30% CR (CR, n = 5) or were fed a standard control diet (CON, n = 5) starting during their peripubertal period. Circulating testosterone (T) levels were measured across a 24-h period after 7 yr of dietary treatment and were found to be similar in CR and CON males; however, maintenance of daily minimum T levels was significantly higher in the CR animals. Semen collection was performed on the same cohort of animals three times per male (CR, n = 4; CON, n = 4) after 8 yr of treatment, and samples were assessed by a variety of measures. Parameters, including semen quality and sperm cell viability and function, showed less variability in semen samples taken from CR males, but overall testicular function and sperm quality were comparable regardless of diet. There is mounting evidence that CR may promote health and longevity in a wide range of organisms, including nonhuman primates. Importantly, our data suggest that moderate CR has no obvious lasting detrimental effect on testicular function and sperm parameters in young adult primates and may in fact help maintain higher levels of circulating T. C1 [Sitzmann, Brandon D.; Leone, Erin H.; Ottinger, Mary Ann] Univ Maryland, Dept Anim & Avian Sci, College Pk, MD 20742 USA. [Sitzmann, Brandon D.; Urbanski, Henryk F.; Zelinski, Mary B.] Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Beaverton, OR USA. [Mattison, Julie A.; Ingram, Donald K.] NIA, Lab Expt Gerontol, NIH, Baltimore, MD 21224 USA. [Ingram, Donald K.; Ottinger, Mary Ann] Louisiana State Univ Syst, Pennington Biomed Res Ctr, Nutr Neurosci & Aging Lab, Baton Rouge, LA USA. [Roth, George S.] GeroScience Inc, Pylesville, MD USA. [Urbanski, Henryk F.] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97201 USA. [Urbanski, Henryk F.] Oregon Hlth & Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97201 USA. RP Ottinger, MA (reprint author), Univ Maryland, Dept Anim & Avian Sci, College Pk, MD 20742 USA. EM maottinger@umresearch.umd.edu FU National Institutes of Health [AG-19914, AG-21380, AG-21382, AG-29612, HD-18185, HD-29186, RR-00163] FX Supported by National Institutes of Health grants AG-19914, AG-21380, AG-21382, AG-29612, HD-18185, HD-29186, and RR-00163. Additional support was provided by the Department of Animal and Avian Sciences at the University of Maryland and the Intramural Research Program of the National Institute on Aging. NR 64 TC 12 Z9 13 U1 1 U2 5 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD OCT PY 2010 VL 83 IS 4 BP 635 EP 640 DI 10.1095/biolreprod.110.084186 PG 6 WC Reproductive Biology SC Reproductive Biology GA 654JI UT WOS:000282163900016 PM 20610809 ER PT J AU Lopez, G Sidransky, E AF Lopez, Grisel Sidransky, Ellen TI Autosomal recessive mutations in the development of Parkinson's disease SO BIOMARKERS IN MEDICINE LA English DT Review DE ATP13A2; DJ1; Gaucher disease; genetics; glucocerebrosidase; parkin; Parkinson's disease; PINK1; recessive; susceptibility ID EARLY-ONSET PARKINSONISM; GAUCHER-DISEASE; ALPHA-SYNUCLEIN; GLUCOCEREBROSIDASE MUTATIONS; PYRAMIDAL DEGENERATION; PROTEASOME INHIBITION; JUVENILE PARKINSONISM; OXIDATIVE STRESS; PINK1 MUTATIONS; DOWN-REGULATION AB Although Parkinson's disease was long considered a nongenetic disorder, it is now clear that there are multiple predisposing genes, and that the disorder can exhibit either Mendelian or non-Mendelian modes of inheritance. The identification of several of these genes has provided important insights into the pathogenesis of this common complex disorder. This article presents an overview of the genes associated with autosomal recessive Parkinson's disease, including Parkin (PARK2), PINK1 (PARK6), DJ1 (PARK7) and ATP13A2 (PARK9). Recently, it was recognized that mutations in the gene encoding glucocerebrosidase, the enzyme deficient in Gaucher disease, are associated with an increased incidence of parkinsonism. While Gaucher disease is an autosomal recessive inherited disorder, patients with Parkinson's disease can be Gaucher heterozygotes or homozygotes. Elucidating the basis for this association may shed light on new disease mechanisms that contribute to the development of parkinsonism. C1 [Lopez, Grisel; Sidransky, Ellen] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. RP Sidransky, E (reprint author), NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. EM sidranse@mail.nih.gov NR 66 TC 8 Z9 8 U1 1 U2 1 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1752-0363 J9 BIOMARK MED JI Biomark. Med. PD OCT PY 2010 VL 4 IS 5 BP 713 EP 721 DI 10.2217/BMM.1096 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 673DD UT WOS:000283638000007 PM 20945983 ER PT J AU Gungormus, M Branco, M Fong, H Schneider, JP Tamerler, C Sarikaya, M AF Gungormus, Mustafa Branco, Monica Fong, Hanson Schneider, Joel P. Tamerler, Candan Sarikaya, Mehmet TI Self assembled bi-functional peptide hydrogels with biomineralization-directing peptides SO BIOMATERIALS LA English DT Article DE Biomineralization; Biomimetic material; Peptide; Hydrogel; Scaffold; Hydroxyapatite ID BETA-SHEET PEPTIDES; MOLECULAR BIOMIMETICS; BONE REGENERATION; COLLAGEN; BIOMATERIALS; SCAFFOLDS; HAIRPIN; DESIGN; POLYPEPTIDES; DEGRADATION AB A peptide-based hydrogel has been designed that directs the formation of hydroxyapatite. MDG1, a twenty-seven residue peptide, undergoes triggered folding to form an unsymmetrical beta-hairpin that self-assembles in response to an increase in solution ionic strength to yield a mechanically rigid, self supporting hydrogel. The C-terminal portion of MDG1 contains a heptapeptide (MLPHHGA) capable of directing the mineralization process. Circular dichroism spectroscopy indicates that the peptide folds and assembles to form a hydrogel network rich in beta-sheet secondary structure. Oscillatory rheology indicates that the hydrogel is mechanically rigid (G'(similar to)-2500 Pa) before mineralization. In separate experiments, mineralization was induced both biochemically and with cementoblast cells. Mineralization-domain had little effect on the mechanical rigidity of the gel. SEM and EDXS show that MDG1 gels are capable of directing the formation of hydroxapatite. Control hydrogels, prepared by peptides either lacking the mineral-directing portion or reversing its sequence, indicated that the heptapeptide is necessary and its actions are sequence specific. Published by Elsevier Ltd. C1 [Gungormus, Mustafa; Fong, Hanson; Tamerler, Candan; Sarikaya, Mehmet] Univ Washington, Seattle, WA 98195 USA. [Branco, Monica; Schneider, Joel P.] NCI, Ctr Canc Res, Biol Chem Lab, Frederick, MD 21701 USA. RP Sarikaya, M (reprint author), Univ Washington, Seattle, WA 98195 USA. EM musgun@u.washington.edu; monica.branco@nih.gov; hfong@u.washington.edu; Joel.Schneider@nih.gov; Candan@u.washington.edu; sarikaya@u.washington.edu RI Gungormus, Mustafa/F-2814-2011; Schneider, Joel/N-2610-2014; OI Tamerler, Candan/0000-0001-7055-1156 FU National Science Foundation through the Genetically Engineered Materials Science & Engineering Center (GEMSEC); MRSEC at UW; NSF-NIRT; NIDCR-NIH [R01 DE01638601] FX This work was supported (MG, HF, CT, MS) mainly by the National Science Foundation through the Genetically Engineered Materials Science & Engineering Center (GEMSEC), an MRSEC at UW and partially by NSF-NIRT. This work was also supported (MB, JPS) by funding from the NIDCR-NIH grant, R01 DE01638601. We acknowledge the cell lines provided by Martha Somerman (UW-Periodontics). NR 50 TC 49 Z9 50 U1 10 U2 109 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 J9 BIOMATERIALS JI Biomaterials PD OCT PY 2010 VL 31 IS 28 BP 7266 EP 7274 DI 10.1016/j.biomaterials.2010.06.010 PG 9 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 642DE UT WOS:000281183000007 PM 20591477 ER PT J AU Nordstrom, RJ Almutairi, A Hillman, EMC AF Nordstrom, Robert J. Almutairi, Adah Hillman, Elizabeth M. C. TI Feature Issue Introduction: Bio-Optics in Clinical Applications, Nanotechnology, and Drug Discovery SO BIOMEDICAL OPTICS EXPRESS LA English DT Article AB The editors introduce the Biomedical Optics Express feature issue, "Bio-Optics in Clinical Applications, Nanotechnology, and Drug Discovery," which combines three technical areas from the 2010 Optical Society of America (OSA), Biomedical Optics (BIOMED) Topical Meeting held on 11-14 April in Miami, FL and includes contributions from conference attendees. (C) 2010 Optical Society of America C1 [Nordstrom, Robert J.] NCI, Canc Imaging Program, NIH, Bethesda, MD 20892 USA. [Almutairi, Adah] Univ Calif San Diego, Lab Biorespons Mat, La Jolla, CA 92093 USA. [Hillman, Elizabeth M. C.] Columbia Univ, Dept Biomed Engn, New York, NY USA. [Hillman, Elizabeth M. C.] Columbia Univ, Dept Radiol, New York, NY USA. RP Nordstrom, RJ (reprint author), NCI, Canc Imaging Program, NIH, 6130 Execut Blvd, Bethesda, MD 20892 USA. NR 7 TC 1 Z9 1 U1 0 U2 3 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 2156-7085 J9 BIOMED OPT EXPRESS JI Biomed. Opt. Express PD OCT 1 PY 2010 VL 1 IS 3 BP 746 EP 747 PG 2 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA V21LM UT WOS:000208209100001 ER PT J AU Yu, BB Saczynski, JS Launer, L AF Yu, Binbing Saczynski, Jane S. Launer, Lenore TI Multiple imputation for estimating the risk of developing dementia and its impact on survival SO BIOMETRICAL JOURNAL LA English DT Article DE Competing risk; Dementia; Illness-death model; Interval censoring; Multiple imputation ID INTERVAL-CENSORED DATA; AGE-SPECIFIC INCIDENCE; PENALIZED LIKELIHOOD APPROACH; ILLNESS-DEATH MODEL; MULTISTATE MODELS; COARSENED OBSERVATIONS; ALZHEIMERS-DISEASE; ASSOCIATION; PREVALENCE; REGRESSION AB Dementia, Alzheimer's disease in particular, is one of the major causes of disability and decreased quality of life among the elderly and a leading obstacle to successful aging. Given the profound impact on public health, much research has focused on the age-specific risk of developing dementia and the impact on survival. Early work has discussed various methods of estimating age-specific incidence of dementia, among which the illness-death model is popular for modeling disease progression. In this article we use multiple imputation to fit multi-state models for survival data with interval censoring and left truncation. This approach allows semi-Markov models in which survival after dementia depends on onset age. Such models can be used to estimate the cumulative risk of developing dementia in the presence of the competing risk of dementia-free death. Simulations are carried out to examine the performance of the proposed method. Data from the Honolulu Asia Aging Study are analyzed to estimate the age-specific and cumulative risks of dementia and to examine the effect of major risk factors on dementia onset and death. C1 [Yu, Binbing; Launer, Lenore] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Saczynski, Jane S.] Univ Massachusetts, Sch Med, Meyers Primary Care Inst, Div Geriatr, Worcester, MA 01605 USA. RP Yu, BB (reprint author), NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. EM yubi@mail.nih.gov FU National Institute on Aging FX The research was supported in part by the Intramural Research Program of the National Institute on Aging. The simulation used the high-performance computational capabilities of the Biowulf Linux cluster at the National Institutes of Health (http://biowulf.nih.gov). The authors wish to thank two anonymous reviewers for their helpful comments. NR 27 TC 5 Z9 5 U1 0 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0323-3847 EI 1521-4036 J9 BIOMETRICAL J JI Biom. J. PD OCT PY 2010 VL 52 IS 5 BP 616 EP 627 DI 10.1002/bimj.200900266 PG 12 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 677RC UT WOS:000284008500004 PM 20976693 ER PT J AU Lee, HW Kim, HO Choi, WJ Choi, S Lee, JH Park, SG Yoo, L Jacobson, KA Jeong, LS AF Lee, Hyuk Woo Kim, Hea Ok Choi, Won Jun Choi, Sun Lee, Jin Hee Park, Seul-gi Yoo, Lena Jacobson, Kenneth A. Jeong, Lak Shin TI Design, synthesis, and binding of homologated truncated 4 '-thioadenosine derivatives at the human A(3) adenosine receptors SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE Homologation; A(3) adenosine receptor; Binding affinity; Truncated 4 '-thioadenosine ID STRUCTURAL DETERMINANTS; SELECTIVE AGONISTS; HIGHLY POTENT; LIGANDS; D-4'-THIOADENOSINE; ANTAGONISTS; EFFICACY AB We synthesized homologated truncated 4'-thioadenosine analogues 3 in which a methylene (CH2) group was inserted in place of the glycosidic bond of a potent and selective A(3) adenosine receptor antagonist 2. The analogues were designed to induce maximum binding interaction in the binding site of the A(3) adenosine receptor. However, all homologated nucleosides were devoid of binding affinity at all subtypes of adenosine receptors, indicating that free rotation through the single bond allowed the compound to adopt an indefinite number of conformations, disrupting the favorable binding interaction essential for receptor recognition. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Lee, Hyuk Woo; Choi, Won Jun; Jeong, Lak Shin] Ewha Womans Univ, Dept Bioinspired Sci, Coll Pharm, Seoul 120750, South Korea. [Kim, Hea Ok; Choi, Sun; Lee, Jin Hee; Park, Seul-gi; Jeong, Lak Shin] Ewha Womans Univ, Coll Pharm, Med Chem Lab, Seoul 120750, South Korea. [Choi, Won Jun] Dongguk Univ, Coll Pharm, Kyonggi Do 410774, South Korea. [Yoo, Lena; Jacobson, Kenneth A.] Natl Inst Diabet Digest Dis & Kidney Dis, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Jeong, LS (reprint author), Ewha Womans Univ, Dept Bioinspired Sci, Coll Pharm, 11-1 Seodaemun Gu, Seoul 120750, South Korea. EM lakjeong@ewha.ac.kr RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Korea Research Foundation [NRF-2008-314-E00304]; NIDDK; Ewha Womans University FX This work was supported by the grant from the Korea Research Foundation (NRF-2008-314-E00304) and the NIDDK Intramural Research Program. H. W. L. acknowledges the research professor fellowship from the Ewha Womans University (2009). NR 14 TC 8 Z9 8 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD OCT 1 PY 2010 VL 18 IS 19 BP 7015 EP 7021 DI 10.1016/j.bmc.2010.08.018 PG 7 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 651YN UT WOS:000281964300008 PM 20826090 ER PT J AU Kim, EJ Love, DC Darout, E Abdo, M Rempel, B Withers, SG Rablen, PR Hanover, JA Knapp, S AF Kim, Eun Ju Love, Dona C. Darout, Etzer Abdo, Mohannad Rempel, Brian Withers, Stephen G. Rablen, Paul R. Hanover, John A. Knapp, Spencer TI OGA inhibition by GlcNAc-selenazoline SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE Woollins reagent; Post-translational modification; Lipophilicity; Hyperglycemia; N-Acetylhexosaminidase; Transcription factor; Transition state ID LINKED N-ACETYLGLUCOSAMINE; O-GLCNACASE; INSULIN-RESISTANCE; TRANSCRIPTIONAL ACTIVITY; STRUCTURAL INSIGHTS; KINETIC-ANALYSIS; FOXO1 INCREASES; NAG-THIAZOLINE; MECHANISM; GLUCOSE AB The title compound, which differs from the powerful O-GlcNAcase (OGA) inhibitor GlcNAc-thiazoline only at the chalcogen atom (Se for S), is a much weaker inhibitor in a direct OGA assay. In human cells, however, the selenazoline shows comparable ability to induce hyper-O-GlcNAc-ylation, and the two show similar reduction of insulin-stimulated translocation of glucose transporter 4 in differentiated 3T3 adipocytes. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Love, Dona C.; Hanover, John A.] NIDDK, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA. [Kim, Eun Ju] Daegu Univ, Dept Sci Educ Chem Major, Gyeongbuk 712714, South Korea. [Darout, Etzer; Abdo, Mohannad; Knapp, Spencer] Rutgers State Univ, Dept Chem & Chem Biol, Piscataway, NJ USA. [Rempel, Brian; Withers, Stephen G.] Univ British Columbia, Dept Chem, Vancouver, BC V6T 1Z1, Canada. [Rablen, Paul R.] Swarthmore Coll, Dept Chem & Biochem, Swarthmore, PA 19081 USA. RP Hanover, JA (reprint author), NIDDK, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA. EM spencer.knapp@rutgers.edu FU NIH [AI055760]; Henry Dreyfus Teacher-Scholar; UNCF-Merck; Canadian Institutes for Health Research; Natural Science and Engineering Research Council; National Institute of Diabetes and Digestive and Kidney Diseases, NIH; National Research Foundation of Korea [20090065] FX We are grateful to NIH (SK, AI055760) and the Henry Dreyfus Teacher-Scholar Awards Program (P.R.R.) for partial financial support, UNCF-Merck for a graduate fellowship to E.D., the Canadian Institutes for Health Research and the Natural Science and Engineering Research Council (S.G.W. and B.R.), the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases, NIH (J.A.H.), and the National Research Foundation of Korea (EJK, 20090065). NR 45 TC 7 Z9 7 U1 0 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD OCT 1 PY 2010 VL 18 IS 19 BP 7058 EP 7064 DI 10.1016/j.bmc.2010.08.010 PG 7 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 651YN UT WOS:000281964300014 PM 20822912 ER PT J AU Shinkre, BA Kumar, TS Gao, ZG Deflorian, F Jacobson, KA Trenkle, WC AF Shinkre, Bidhan A. Kumar, T. Santhosh Gao, Zhan-Guo Deflorian, Francesca Jacobson, Kenneth A. Trenkle, William C. TI Synthesis and evaluation of 1,2,4-triazolo[1,5-c]pyrimidine derivatives as A(2A) receptor-selective antagonists SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE Nucleoside; G Protein-coupled receptor; Molecular modelling; Adenosine receptor; Radioligand binding ID ADENOSINE RECEPTOR; PARKINSONS-DISEASE; POTENT; RADIOLIGAND; RAT; DESIGN; BRAIN AB Movement disorders such as Parkinson's disease and Huntington's disease are serious life-limiting and debilitating movement disorders. Their onset typically occurs from mid-life to late in life, and effective diagnostic techniques for detecting and following the disease course are lacking. Our goal is to develop receptor imaging agents for positron emission tomography (PET) that selectively target the most relevant subtype of adenosine receptors (AR) that are highly expressed in the striatum, that is, the A(2A) AR. To further this goal, we have synthesized and characterized pharmacologically a family of high affinity A(2A) AR ligands, based on the known antagonist, SCH 442416 (R = -Me), which have structural variability on the terminus (R = -Et, -i-Pr, -allyl, and others). A O-fluoroethyl analogue suitable for use as a PET tracer had a K-i value of 12.4 nM and was highly selective for the A(2A) AR in comparison to the A(1) and A(3) ARs. Published by Elsevier Ltd. C1 [Kumar, T. Santhosh; Gao, Zhan-Guo; Deflorian, Francesca; Jacobson, Kenneth A.] NIDDKD, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. [Shinkre, Bidhan A.; Trenkle, William C.] NIDDKD, Chem Biol Unit, Lab Cell Biol & Biochem, NIH,NIDDK,LCBB, Bethesda, MD 20892 USA. RP Jacobson, KA (reprint author), NIDDKD, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. EM wtrenkle@niddk.nih.gov RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU NIH, National Institute of Diabetes and Digestive and Kidney Diseases FX This research was supported in part by the Intramural Research Program of the NIH, National Institute of Diabetes and Digestive and Kidney Diseases. We thank Dale Kiesewetter, Abesh Bhattacharjee, and Lixin Lang (NIH, NIBIB) for helpful discussion. NR 25 TC 11 Z9 11 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD OCT 1 PY 2010 VL 20 IS 19 BP 5690 EP 5694 DI 10.1016/j.bmcl.2010.08.021 PG 5 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 648ZY UT WOS:000281735600019 PM 20801028 ER PT J AU Mills, JL AF Mills, James L. TI Malformations in Infants of Diabetic Mothers SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Article ID CONGENITAL HEART-DISEASE; INSULIN; PREGNANCY; CHILDREN; WOMEN; BORN; RATS; MICE AB Maternal insulin-dependent diabetes has long been associated with congenital malformations. As other causes of mortality and morbidity have been eliminated or reduced, malformations have become increasingly prominent. Although there is not universal agreement, the great majority of investigators find a two- to threefold increase in malformations in infants of insulin-dependent diabetic mothers. This increase is not seen in infants of gestational diabetics. It probably is not present in women whose diabetes can be controlled by diet or oral hypoglycemic agents. The risk does not appear to be primarily genetic since diabetic fathers do not have an increased number of malformed offspring. Most studies show a generalized increase in malformations involving multiple organ systems. Multiple malformations seem to be more common in diabetic than nondiabetic infants. Caudal regression has the strongest association with diabetes, occurring roughly 200 times more frequently in infants of diabetic mothers than in other infants. The teratogenic mechanism in diabetes is not known. Hyperglycemia may be important but human studies focusing on the period of organogenesis are lacking. Hypoglycemia has also been suggested based mainly on animal experiments. Insulin appears unlikely. Numerous other factors including vascular disease, hypoxia, ketone and amino acid abnormalities, glycosylation of proteins, or hormone imbalances could be teratogenic. None has been studied in sufficient detail to make a judgment. A large-scale prospective study is required to determine early fetal loss rates, correlate metabolic status during organogenesis with outcome, and assess the effect of diabetic control on malformation rates. C1 NICHD, EBRP, NICHHD, NIH, Bethesda, MD 20205 USA. RP Mills, JL (reprint author), NICHD, EBRP, NICHHD, NIH, Landow Bldg,Room 8B06, Bethesda, MD 20205 USA. FU Intramural NIH HHS [Z99 HD999999] NR 39 TC 2 Z9 2 U1 0 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD OCT PY 2010 VL 88 IS 10 SI SI BP 769 EP 778 PG 10 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 673DH UT WOS:000283638500003 PM 20973049 ER PT J AU Grauer, O Wolff, D Bertz, H Greinix, H Kuhl, JS Lawitschka, A Lee, SJ Pavletic, SZ Holler, E Kleiter, I AF Grauer, Oliver Wolff, Daniel Bertz, Hartmut Greinix, Hildegard Kuehl, Joern-Sven Lawitschka, Anita Lee, Stephanie J. Pavletic, Steven Z. Holler, Ernst Kleiter, Ingo TI Neurological manifestations of chronic graft-versus-host disease after allogeneic haematopoietic stem cell transplantation: report from the Consensus Conference on Clinical Practice in chronic graft-versus-host disease SO BRAIN LA English DT Review DE chronic graft-versus-host disease; allogeneic haematopoietic stem cell transplantation; neurologic manifestations; supportive care ID BONE-MARROW-TRANSPLANTATION; GUILLAIN-BARRE-SYNDROME; CENTRAL-NERVOUS-SYSTEM; DONOR LYMPHOCYTE INFUSION; INFLAMMATORY DEMYELINATING POLYNEUROPATHY; CHRONIC MYELOID-LEUKEMIA; SOLID-ORGAN TRANSPLANTATION; IMMUNE-MEDIATED MYELOPATHY; WORKING GROUP-REPORT; MYASTHENIA-GRAVIS AB A major obstacle of allogeneic haematopoietic stem cell transplantation is graft-versus-host disease, an immune-mediated disorder that affects multiple tissues and organs with varying severity. Neurological complications of acute and chronic graft-versus-host disease are rare but can produce severe clinical problems with significant morbidity and mortality. In this article, we review neurological manifestations of chronic graft-versus-host disease that comprise immune-mediated neuropathies, myasthenia gravis and myositis in the peripheral nervous system and various cerebrovascular complications, demyelination and immune-mediated encephalitis in the central nervous system. The National Institutes of Health consensus on criteria for clinical trials in chronic graft-versus-host disease recommended that the diagnosis of chronic graft-versus-host disease of the nervous system can be made only when other organs are affected by graft-versus-host disease and frequent neurological differential diagnoses such as drug-induced toxicities or opportunistic infections are excluded. The Consensus Conference on Clinical Practice in chronic graft-versus-host disease, held in autumn 2009 in Regensburg, aimed to summarize the literature and to provide guidelines for the diagnostic approach in children and adults with neurological manifestations of chronic graft-versus-host disease. Moreover, we present therapeutic recommendations and their level of evidence for the management of these complications. Overlapping symptoms and comorbidities after allogeneic haematopoietic stem cell transplantation and the limited knowledge about the underlying biological mechanisms of chronic graft-versus-host disease affecting the nervous system emphasize the need for further experimental and clinical investigations. C1 [Grauer, Oliver; Kleiter, Ingo] Univ Med Ctr Regensburg, Dept Neurol, D-93053 Regensburg, Germany. [Wolff, Daniel; Holler, Ernst] Univ Med Ctr Regensburg, Dept Haematol & Internal Oncol, D-93053 Regensburg, Germany. [Bertz, Hartmut] Univ Med Ctr Freiburg, Dept Haematol & Oncol, D-79106 Freiburg, Germany. [Greinix, Hildegard] Med Univ Vienna, Dept Internal Med 1, A-1090 Vienna, Austria. [Lawitschka, Anita] St Anna Childrens Hosp, A-1090 Vienna, Austria. [Kuehl, Joern-Sven] Charite Campus Virchow Klinikum, Dept Paediat Haematol & Oncol, D-13353 Berlin, Germany. [Lee, Stephanie J.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA. [Pavletic, Steven Z.] Natl Canc Inst, Ctr Canc Res, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. RP Kleiter, I (reprint author), Univ Med Ctr Regensburg, Dept Neurol, Univ Str 84, D-93053 Regensburg, Germany. EM ingo.kleiter@klinik.uni-regensburg.de NR 138 TC 40 Z9 42 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD OCT PY 2010 VL 133 BP 2852 EP 2865 DI 10.1093/brain/awq245 PN 10 PG 14 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 657OX UT WOS:000282423100004 PM 20846944 ER PT J AU Deep-Soboslay, A Hyde, TM Callicott, JP Lener, MS Verchinski, BA Apud, JA Weinberger, DR Elvevag, B AF Deep-Soboslay, Amy Hyde, Thomas M. Callicott, Joseph P. Lener, Marc S. Verchinski, Beth A. Apud, Jose A. Weinberger, Daniel R. Elvevag, Brita TI Handedness, heritability, neurocognition and brain asymmetry in schizophrenia SO BRAIN LA English DT Article DE schizophrenia; handedness; neurocognition; brain asymmetry ID REVERSED CEREBRAL ASYMMETRY; MONOZYGOTIC TWINS; PLANUM TEMPORALE; HAND PREFERENCE; BIOLOGICAL RELATIVES; GENETIC RISK; DISORDER; LANGUAGE; MRI; LATERALIZATION AB Higher rates of non-right-handedness (i.e. left- and mixed-handedness) have been reported in schizophrenia and have been a centrepiece for theories of anomalous lateralization in this disorder. We investigated whether non-right-handedness is (i) more prevalent in patients as compared with unaffected siblings and healthy unrelated control participants; (ii) familial; (iii) associated with disproportionately poorer neurocognition; and (iv) associated with grey matter volume asymmetries. We examined 1445 participants (375 patients with schizophrenia, 502 unaffected siblings and 568 unrelated controls) using the Edinburgh Handedness Inventory, a battery of neuropsychological tasks and structural magnetic resonance imaging data. Patients displayed a leftward shift in Edinburgh Handedness Inventory laterality quotient scores as compared with both their unaffected siblings and unrelated controls, but this finding disappeared when sex was added to the model. Moreover, there was no evidence of increased familial risk for non-right-handedness. Non-right-handedness was not associated with disproportionate neurocognitive disadvantage or with grey matter volume asymmetries in the frontal pole, lateral occipital pole or temporal pole. Non-right-handedness was associated with a significant reduction in left asymmetry in the superior temporal gyrus in both patients and controls. Our data neither provide strong support for 'atypical' handedness as a schizophrenia risk-associated heritable phenotype nor that it is associated with poorer neurocognition or anomalous cerebral asymmetries. C1 [Deep-Soboslay, Amy; Hyde, Thomas M.; Callicott, Joseph P.; Lener, Marc S.; Verchinski, Beth A.; Apud, Jose A.; Weinberger, Daniel R.; Elvevag, Brita] NIMH, CBDB, NIH, Bethesda, MD 20892 USA. RP Elvevag, B (reprint author), NIMH, CBDB, NIH, 10 Ctr Dr,MSC 1379, Bethesda, MD 20892 USA. EM brita@elvevaag.net RI Callicott, Joseph/C-9102-2009 OI Callicott, Joseph/0000-0003-1298-3334 FU National Institute of Mental Health, National Institutes of Health FX Intramural Research Program of the National Institute of Mental Health, National Institutes of Health. NR 70 TC 24 Z9 24 U1 3 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD OCT PY 2010 VL 133 BP 3113 EP 3122 DI 10.1093/brain/awq160 PN 10 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 657OX UT WOS:000282423100024 PM 20639549 ER PT J AU Dey, S Soliman, AS Hablas, A Seifeldein, IA Ismail, K Ramadan, M El-Hamzawy, H Wilson, ML Banerjee, M Boffetta, P Harford, J Merajver, SD AF Dey, Subhojit Soliman, Amr S. Hablas, Ahmad Seifeldein, Ibrahim A. Ismail, Kadry Ramadan, Mohamed El-Hamzawy, Hesham Wilson, Mark L. Banerjee, Mousumi Boffetta, Paolo Harford, Joe Merajver, Sofia D. TI Urban-rural differences in breast cancer incidence in Egypt (1999-2006) SO BREAST LA English DT Article DE Breast cancer; Incidence; Urban-rural; xenoestrogens; Egypt ID PERSISTENT ORGANIC POLLUTANTS; PASSIVE AIR SAMPLERS; BISPHENOL-A; ORGANOCHLORINE PESTICIDES; POLYCHLORINATED-BIPHENYLS; US POPULATION; WASTE-WATER; ENVIRONMENT; EXPOSURE; MORTALITY AB Objective: To describe urban rural differences in breast cancer incidence in Gharbiah, Egypt and to investigate if these differences could be explained by known risk factors of breast cancer. Methods: We used data from the population-based cancer registry of Gharbiah, Egypt to assess breast cancer incidence from 1999 through 2006. The Egyptian census provided data on district-specific population, age, and urban rural classification. Incidence patterns of breast cancer by district and age-specific urban rural differences were analyzed. Results: Overall, incidence rate of breast cancer was three to four times higher in urban areas than in rural areas (60.9/10(5)-year for urban areas versus 17.8/10(5)-year for rural areas; IRR = 3.73, 95% CI = 3.30, 4.22). Urban areas had consistently higher incidence of breast cancer across all age-groups for all years. Higher incidence of breast cancer was also seen in the more developed districts of Tanta and El-Mehalla. Conclusions: Higher incidence of breast cancer in urban and more developed populations might be related to higher exposure to xenoestrogens, as well as other endocrine disruptors and genotoxic substances. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Dey, Subhojit; Soliman, Amr S.; Wilson, Mark L.] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA. [Hablas, Ahmad; Ismail, Kadry] Gharbiah Canc Soc, Tanta, Gharbiah, Egypt. [Seifeldein, Ibrahim A.; Ramadan, Mohamed; El-Hamzawy, Hesham] Tanta Canc Ctr, Tanta, Gharbiah, Egypt. [Banerjee, Mousumi] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA. [Boffetta, Paolo] Mt Sinai Sch Med, Tisch Canc Inst, New York, NY USA. [Harford, Joe] NCI, Off Int Affairs, Bethesda, MD 20892 USA. [Merajver, Sofia D.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. RP Dey, S (reprint author), Univ Michigan, Sch Publ Hlth, Dept Epidemiol, 109 Observ St, Ann Arbor, MI 48109 USA. EM subhojit@umich.edu FU Middle East Cancer Consortium, National Cancer Institute, Bethesda [R25 CA112383, R03 CA117350,5, R03 CA117355, P30 CA46592]; Burroughs Wellcome Fund; Breast Cancer Research Foundation; Department of Epidemiology, University of Michigan School of Public Health; Rackham Graduate School of the University of Michigan FX This work was supported by the Middle East Cancer Consortium, National Cancer Institute, Bethesda [R25 CA112383, R03 CA117350,5 P30 CA46592], the Burroughs Wellcome Fund [SDM], and the Breast Cancer Research Foundation [SDM]. Block Grant of the Department of Epidemiology, University of Michigan School of Public Health; and the Travel Grant of the Rackham Graduate School of the University of Michigan to [SD]. NR 45 TC 27 Z9 28 U1 0 U2 4 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0960-9776 J9 BREAST JI Breast PD OCT PY 2010 VL 19 IS 5 BP 417 EP 423 DI 10.1016/j.breast.2010.04.005 PG 7 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 673XF UT WOS:000283696800021 PM 20452771 ER PT J AU Soldati, R Wargon, V Cerliani, JP Giulianelli, S Vanzulli, SI Gorostiaga, MA Bolado, J do Campo, P Molinolo, A Vollmer, G Lanari, C AF Soldati, Rocio Wargon, Victoria Pablo Cerliani, Juan Giulianelli, Sebastian Ines Vanzulli, Silvia Alicia Gorostiaga, Maria Bolado, Julieta do Campo, Pablo Molinolo, Alfredo Vollmer, Guenter Lanari, Claudia TI Inhibition of mammary tumor growth by estrogens: is there a specific role for estrogen receptors alpha and beta? SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Aif, apoptosis; Bax; Bcl-xl; Breast cancer; Caspase-9; DPN; Estrogen receptors alpha; Estrogen receptors beta; Mammary carcinomas; PPT; Progesterone receptors; Tumor regression ID BREAST-CANCER-CELLS; APOPTOSIS-INDUCING FACTOR; ER-BETA; GENE-EXPRESSION; PROGESTERONE-RECEPTORS; EXPERIMENTAL-MODEL; DUCTAL CARCINOMAS; IN-VIVO; REGRESSION; ESTRADIOL AB To evaluate the extent to which each estrogen receptor (ER) subtype contributes to the stimulation or to the inhibition of mammary tumor growth, we evaluated the effects of specific agonists in MC4-L2 cells, which are stimulated by 17 beta-estradiol (E(2)), and in mammary carcinomas of the MPA mouse breast cancer model, which are inhibited by E(2). Both express ER alpha and ER beta. In MC4-L2 cells, 4,4',4 ''-(4-propyl-(1H)-pyrazole-1,3,5-triyl) trisphenol (PPT; ER alpha agonist) and (4-hydroxy-phenyl)-propionitrile (DPN; ER beta agonist) stimulated cell proliferation, whereas the opposite occurred in C4-HI primary cultures. The inhibitory effect was associated with a decrease in ER alpha and cyclin D1 expression and an increase in progesterone receptor (PR) expression as well as in the Bax/Bcl-xl ratio. In vivo, mice carrying C4-HI or 32-2-HI tumors were treated with E(2), PPT or DPN (3 mg/kg/day) or with vehicle. PPT and DPN inhibited tumor size, as did E(2), during the first 72 h. After a few days, DPN-treated tumors started to grow again, while PPT-treated tumors remained quiescent for a longer period of time. A pronounced decrease in the mitotic index and an increase in the apoptotic index was associated with tumor regresion. All treated tumors showed: (a) an increase in integrin alpha 6 and Bax expression, (b) an increased stromal laminin redistribution, and (c) a decrease in ERa, Bcl-xl and Bcl-2 expression (P < 0.001). Apoptosis-inducing factor (Aif) expression was increased in DPN-treated tumors, while active caspase 9 was up-regulated in PPT-treated mice, demonstrating the involvement of the intrinsic apoptotic pathway in estrogen-induced regression in this model. In conclusion, our data indicate that although there may be some preferences for activation pathways by the different agonists, the stimulatory or inhibitory effects triggered by estrogens are cell-context dependent rather than ER isoform dependent. C1 [Soldati, Rocio; Wargon, Victoria; Pablo Cerliani, Juan; Giulianelli, Sebastian; Alicia Gorostiaga, Maria; Bolado, Julieta; do Campo, Pablo; Lanari, Claudia] Natl Res Council Argentina CONICET, Inst Expt Biol & Med IBYME, Lab Hormonal Carcinogenesis, RA-1428 Buenos Aires, DF, Argentina. [Ines Vanzulli, Silvia] Natl Acad Med Buenos Aires, Buenos Aires, DF, Argentina. [Molinolo, Alfredo] Natl Inst Dent & Craniofacial Res, NIH, Oral & Pharyngeal Canc Branch, Bethesda, MD USA. [Vollmer, Guenter] Tech Univ Dresden, Dept Biol, Lab Mol Cell Physiol & Endocrinol, D-01062 Dresden, Germany. RP Lanari, C (reprint author), Natl Res Council Argentina CONICET, Inst Expt Biol & Med IBYME, Lab Hormonal Carcinogenesis, RA-1428 Buenos Aires, DF, Argentina. EM clanari@dna.uba.ar FU Fundacion Sales and SECyT [PICT 05, 05-14406, PICT 05-05-38302]; DFG [Vo410/6-4]; Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD FX We are very grateful to Dr. F Parborell for her advice on apoptosis evaluation and to Laboratorios Craveri, Buenos Aires for providing MPA depot. The authors declare that they have no competing interests. This work was supported by Fundacion Sales and SECyT (PICT 05, 05-14406). DAAD-SECYT supported short visits for RS to Germany and to GV to Buenos Aires. RS was awarded by Avon Foundation for data presentation at the AACR, Breast Cancer Meeting at San Diego 2007.; Sales Foundation, SECyT (PICT 05-05-38302), DFG Vo410/6-4. Dr. Molinolo is supported by the Intramural Research Program of the Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD. NR 62 TC 5 Z9 6 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD OCT PY 2010 VL 123 IS 3 BP 709 EP 724 DI 10.1007/s10549-009-0659-8 PG 16 WC Oncology SC Oncology GA 651BQ UT WOS:000281900000010 PM 20012353 ER PT J AU Goldin, LR Lanasa, MC Slager, SL Cerhan, JR Vachon, CM Strom, SS Camp, NJ Spector, LG Leis, JF Morrison, VA Glenn, M Rabe, KG Achenbach, SJ Algood, SD Abbasi, F Fontaine, L Yau, M Rassenti, LZ Kay, NE Call, TG Hanson, CA Weinberg, JB Marti, GE Caporaso, NE AF Goldin, Lynn R. Lanasa, Mark C. Slager, Susan L. Cerhan, James R. Vachon, Celine M. Strom, Sara S. Camp, Nicola J. Spector, Logan G. Leis, Jose F. Morrison, Vicki A. Glenn, Martha Rabe, Kari G. Achenbach, Sara J. Algood, Sallie D. Abbasi, Fatima Fontaine, Laura Yau, Michelle Rassenti, Laura Z. Kay, Neil E. Call, Timothy G. Hanson, Curtis A. Weinberg, J. Brice Marti, Gerald E. Caporaso, Neil E. TI Common occurrence of monoclonal B-cell lymphocytosis among members of high-risk CLL families SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE chronic lymphocytic leukaemia; high risk families; monoclonal B-cell lymphocytosis; flow cytometry ID NATURAL-HISTORY; FLOW-CYTOMETRY; LEUKEMIA; BLOOD; GUIDELINES; DIAGNOSIS; RELATIVES; CLONES AB P>Monoclonal B-cell lymphocytosis (MBL) is an asymptomatic haematological condition characterized by low absolute levels of B-cell clones with a surface immunophenotype similar to that of chronic lymphocytic leukaemia (CLL). In the general population, MBL increases with age with a prevalence of 5-9% in individuals over age 60 years. It has been reported to be higher among first-degree relatives from CLL families. We report results of multi-parameter flow cytometry among 505 first-degree relatives with no personal history of lymphoproliferative disease from 140 families having at least two cases of CLL. Seventeen percent of relatives had MBL. Age was the most important determinant where the probability for developing MBL by age 90 years was 61%. MBL clustered in certain families but clustering was independent of the number of known CLL cases in a family. As is the case with CLL, males had a significantly higher risk for MBL than did females (P = 0 center dot 04). MBL patients had significantly higher mean absolute lymphocyte counts (2 center dot 4 x 109/l) and B-cell counts (0 center dot 53 x 109/l) than those with a normal B-cell immuno-phenotype. Our findings show that MBL occurs at a very high rate in high risk CLL families. Both the age and gender distribution of MBL are parallel to CLL, implying a shared inherited risk. C1 [Goldin, Lynn R.] NCI, Genet Epidemiol Branch, DCEG, Bethesda, MD 20892 USA. [Lanasa, Mark C.; Algood, Sallie D.; Weinberg, J. Brice] Duke Univ, Med Ctr, Durham, NC USA. [Slager, Susan L.; Cerhan, James R.; Vachon, Celine M.; Rabe, Kari G.; Achenbach, Sara J.; Kay, Neil E.; Call, Timothy G.; Hanson, Curtis A.] Mayo Clin, Coll Med, Rochester, MN USA. [Strom, Sara S.] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA. [Camp, Nicola J.; Glenn, Martha] Univ Utah, Salt Lake City, UT USA. [Spector, Logan G.; Morrison, Vicki A.] Univ Minnesota, Minneapolis, MN USA. [Leis, Jose F.] Mayo Clin Arizona, Phoenix, AZ USA. [Morrison, Vicki A.] VA Med Ctr, Minneapolis, MN USA. [Abbasi, Fatima; Marti, Gerald E.] US FDA, Cellular & Tissue Therapy Branch, CBER, OCTGC, Rockville, MD USA. [Fontaine, Laura] Westat Corp, Rockville, MD USA. [Rassenti, Laura Z.] Moores UCSD Canc Ctr, La Jolla, CA USA. [Weinberg, J. Brice] VA Med Ctr, Durham, NC USA. RP Goldin, LR (reprint author), NCI, Genet Epidemiol Branch, DCEG, 6120 Execut Blvd,Rm 7008,MSC 7236, Bethesda, MD 20892 USA. EM goldinl@mail.nih.gov OI Cerhan, James/0000-0002-7482-178X; Spector, Logan/0000-0003-2516-0222 FU National Cancer Institute, National Institutes of Health, Bethesda, Maryland; National Cancer Institute [CA118444, CA116237, CA137941, N01-PC-35141]; Leukemia and Lymphoma Society [61006]; Veterans Affairs Research Service; National Institutes of Health [AI-51445] FX This material is based upon work supported by the Intramural Program of the National Cancer Institute, National Institutes of Health, Bethesda, Maryland, and by grants CA118444 and CA116237 from the National Cancer Institute. JBW is also supported in part by grant CA137941 from the National Cancer Institute, grant # 61006 from the Leukemia and Lymphoma Society, and the Veterans Affairs Research Service. MCL is a Fellow of the Leukemia and Lymphoma Society of America. Flow cytometry was performed in the Duke Human Vaccine Institute Flow Cytometry Core Facility that is supported by the National Institutes of Health award AI-51445. Data collection in Utah was made possible by the Utah Population DataBase (UPDB) and the Utah Cancer Registry (UCR). Partial support for all data in the UPDB was provided by the University of Utah Huntsman Cancer Institute. The UCR is funded by contract N01-PC-35141 from the NCI's SEER program with additional support from the Utah State Department of Health and the University of Utah. NR 22 TC 29 Z9 31 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD OCT PY 2010 VL 151 IS 2 BP 152 EP 158 DI 10.1111/j.1365-2141.2010.08339.x PG 7 WC Hematology SC Hematology GA 656XN UT WOS:000282374500004 PM 20738309 ER PT J AU Luke, NS DeVito, MJ Shah, I El-Masri, HA AF Luke, Nicholas S. DeVito, Michael J. Shah, Imran El-Masri, Hisham A. TI Development of a Quantitative Model of Pregnane X Receptor (PXR) Mediated Xenobiotic Metabolizing Enzyme Induction SO BULLETIN OF MATHEMATICAL BIOLOGY LA English DT Article DE Nuclear receptors; Mathematical model; Gene induction ID CYP3A4 GENE-EXPRESSION; NUCLEAR RECEPTORS; INTERINDIVIDUAL VARIABILITY; DRUG-INTERACTIONS; LIVER; RIFAMPICIN; TRANSCRIPTION; ACTIVATION; PATHWAYS; LIGANDS AB The pregnane X receptor plays an integral role in the regulation of hepatic metabolism. It has been shown to regulate CYP3A4, which is the most abundant cytochrome P450 in the human liver. With its large and flexible ligand-binding domain, PXR can be activated by an enormous range of relatively small, hydrophobic, exogenous compounds. Upon activation, PXR partners with the retinoid X receptor (RXR) to form a heterodimer. The newly formed heterodimer binds to an appropriate DNA response element, causing increased transcription. This leads to an induction in the level of CYP3A4. These mechanistic steps are included into a biologically-based mathematical model. The quantitative model predicts fold level inductions of CYP3A4 mRNA and protein in response to PXR activation. Model parameter values have been taken from literature when appropriate. Unknown parameter values are estimated by optimizing the model results to published in vivo and in vitro data sets. A sensitivity analysis is performed to evaluate the model structure and identify future data needs which would be critical to revising the model. C1 [Luke, Nicholas S.] N Carolina Agr & Tech State Univ, Dept Math, Greensboro, NC 27411 USA. [DeVito, Michael J.] NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. [El-Masri, Hisham A.] US EPA, ORD, NHEERL, Integrated Syst Toxicol Div, Res Triangle Pk, NC 27711 USA. [Shah, Imran] US EPA, ORD, Natl Ctr Computat Toxicol, Res Triangle Pk, NC 27711 USA. RP Luke, NS (reprint author), N Carolina Agr & Tech State Univ, Dept Math, Greensboro, NC 27411 USA. EM luke@ncat.edu; Michael.Devito@nih.gov; shah.imran@epa.gov; el-masri.hisham@epa.gov NR 41 TC 2 Z9 3 U1 3 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0092-8240 J9 B MATH BIOL JI Bull. Math. Biol. PD OCT PY 2010 VL 72 IS 7 BP 1799 EP 1819 DI 10.1007/s11538-010-9508-5 PG 21 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA 657QR UT WOS:000282427900007 PM 20151218 ER PT J AU Minasian, LM Carpenter, WR Weiner, BJ Anderson, DE McCaskill-Stevens, W Nelson, S Whitman, C Kelaghan, J O'Mara, AM Kaluzny, AD AF Minasian, Lori M. Carpenter, William R. Weiner, Bryan J. Anderson, Darrell E. McCaskill-Stevens, Worta Nelson, Stefanie Whitman, Cynthia Kelaghan, Joseph O'Mara, Ann M. Kaluzny, Arnold D. TI Translating Research Into Evidence-Based Practice The National Cancer Institute Community Clinical Oncology Program SO CANCER LA English DT Review DE translational research; evidence-based medicine; research and technology; organization and delivery of care; quality of care ID HER2-POSITIVE BREAST-CANCER; RECEPTOR-POSITIVE TUMORS; PREVENTION TRIAL SELECT; HEALTH-CARE; COLORECTAL-CANCER; VITAMIN-E; ADJUVANT CHEMOTHERAPY; IMPLEMENTING EVIDENCE; MONOCLONAL-ANTIBODY; MEDICAL-CARE AB The recent rapid acceleration of basic science is reshaping both our clinical research system and our healthcare delivery system. The pace and growing volume of medical discoveries are yielding exciting new opportunities, yet we continue to face old challenges to maintain research progress and effectively translate research into practice. The National Institutes of Health and individual government programs increasingly are emphasizing research agendas that involve evidence development, comparative-effectiveness research among heterogeneous populations, translational research, and accelerating the translation of research into evidence-based practice as well as building successful research networks to support these efforts. For more than 25 years, the National Cancer Institute Community Clinical Oncology Program has successfully extended research into the community and facilitated the translation of research into evidence-based practice. By describing its keys to success, this article provides practical guidance to cancer-focused, provider-based research networks as well as those in other disciplines. Cancer 2010;116:4440-9. (C) 2010 American Cancer Society. C1 [Carpenter, William R.; Weiner, Bryan J.; Kaluzny, Arnold D.] Univ N Carolina, Dept Hlth Policy & Management, Gillings Sch Global Publ Hlth, Chapel Hill, NC 27599 USA. [Minasian, Lori M.; McCaskill-Stevens, Worta; Whitman, Cynthia; Kelaghan, Joseph; O'Mara, Ann M.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. [Carpenter, William R.; Weiner, Bryan J.; Kaluzny, Arnold D.] Univ N Carolina, Cecil G Sheps Ctr Hlth Serv Res, Chapel Hill, NC 27599 USA. [Carpenter, William R.; Weiner, Bryan J.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Carpenter, William R.] N Carolina Comprehens Canc Program, Raleigh, NC USA. [Anderson, Darrell E.; Nelson, Stefanie] Sci Consulting Grp Inc, Gaithersburg, MD USA. RP Carpenter, WR (reprint author), Univ N Carolina, Dept Hlth Policy & Management, Gillings Sch Global Publ Hlth, 1102A McGavran Greenberg Hall,CB 7411, Chapel Hill, NC 27599 USA. EM bill.carpenter@unc.edu RI Carpenter, William/E-5125-2013 FU NCI NIH HHS [HHSN261200800726P]; PHS HHS [HHSN261200800726P] NR 62 TC 40 Z9 40 U1 0 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD OCT 1 PY 2010 VL 116 IS 19 BP 4440 EP 4449 DI 10.1002/cncr.25248 PG 10 WC Oncology SC Oncology GA 655QA UT WOS:000282263300003 PM 20572032 ER PT J AU Choi, BS Alberti, DB Schelman, WR Kolesar, JM Thomas, JP Marnocha, R Eickhoff, JC Ivy, SP Wilding, G Holen, KD AF Choi, Brian S. Alberti, Dona B. Schelman, William R. Kolesar, Jill M. Thomas, James P. Marnocha, Rebecca Eickhoff, Jens C. Ivy, S. Percy Wilding, George Holen, Kyle D. TI The maximum tolerated dose and biologic effects of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP) in combination with irinotecan for patients with refractory solid tumors SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE Triapine (R); 3-AP; Irinotecan; ABCB1; UGT1A1 ID RIBONUCLEOTIDE REDUCTASE INHIBITOR; PHASE-I; OVARIAN-CANCER; TRIAPINE; TRIAL; POLYMORPHISMS AB Purpose 3-AP is a ribonucleotide reductase inhibitor and has been postulated to act synergistically with other chemotherapeutic agents. This study was conducted to determine the toxicity and antitumor activity of 3-AP with irinotecan. Correlative studies included pharmacokinetics and the effects of ABCB1 and UGT1A1 polymorphisms. Methods The treatment plan consisted of irinotecan on day 1 with 3-AP on days 1-3 of a 21-day cycle. Starting dose was irinotecan 150 mg/m2 and 3-AP 85 mg/m2 per day. Polymorphisms of ABCB1 were evaluated by pyrosequencing. Drug concentrations were determined by HPLC. Results Twenty-three patients were enrolled, 10 men and 13 women. Tumor types included seven patients with pancreatic cancer, four with lung cancer, two with cholangiocarcinoma, two with mesothelioma, two with ovarian cancer, and six with other malignancies. Two patients experienced dose-limiting toxicity (DLT) at dose level 1, requiring amendment of the dose-escalation scheme. Maximal tolerated dose (MTD) was determined to be 3-AP 60 mg/m2 per day and irinotecan 200 mg/m2. DLTs consisted of hypoxia, leukopenia, fatigue, infection, thrombocytopenia, dehydration, and ALT elevation. One partial response in a patient with refractory non-small cell lung cancer was seen. Genotyping suggests that patients with wild-type ABCB1 have a higher rate of grade 3 or 4 toxicity than those with ABCB1 mutations. Conclusions The MTD for this combination was 3-AP 60 mg/m2 per day on days 1-3 and irinotecan 200 mg/m2 on day 1 every 21 days. Antitumor activity in a patient with refractory non-small cell lung cancer was noted at level 1. C1 [Choi, Brian S.; Alberti, Dona B.; Schelman, William R.; Kolesar, Jill M.; Marnocha, Rebecca; Eickhoff, Jens C.; Wilding, George; Holen, Kyle D.] Univ Wisconsin, Paul P Carbone Comprehens Canc Ctr, Madison, WI 53792 USA. [Thomas, James P.] Ohio State Univ, Columbus, OH 43210 USA. [Ivy, S. Percy] NCI, Invest Drug Branch, Canc Therapy Evaluat Program, Div Canc Treatment & Ctr, Bethesda, MD 20892 USA. RP Holen, KD (reprint author), Univ Wisconsin, Paul P Carbone Comprehens Canc Ctr, 600 Highland Ave,K4-528, Madison, WI 53792 USA. EM kdh@medicine.wisc.edu FU NCI [U01CA062491]; NIH [1ULRR025011]; CTEP Translational Research Initiative [24XS090] FX This study was supported by the following grants: U01CA062491 "Early Clinical Trials of Anti-Cancer Agents with Phase I Emphasis", NCI; 1ULRR025011 "Clinical and Translational Science Award of the National Center for Research Resources", NIH; CTEP Translational Research Initiative Funding 24XS090. The authors would like to thank Marcy Pomplun and Zhisheng Jiang of the University of Wisconsin Paul P. Carbone Comprehensive Cancer Center (UWCCC) Analytical Instrumentation Laboratory for Pharmacokinetics, Pharmacodynamics & Pharmacogenetics (3P Lab) for support in the acquisition of 3-AP pharmacokinetics for this research. The authors would also like to thank the nurses and research specialists of the UWCCC Phase I Program for their efforts in conducting and managing this trial. NR 22 TC 9 Z9 9 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD OCT PY 2010 VL 66 IS 5 BP 973 EP 980 DI 10.1007/s00280-010-1250-z PG 8 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 638VH UT WOS:000280924900019 PM 20127092 ER PT J AU Alam, SS Cantwell, MM Cardwell, CR Cook, MB Murray, LJ AF Alam, Shama S. Cantwell, Marie M. Cardwell, Chris R. Cook, Michael B. Murray, Liam J. TI Maternal body mass index and risk of testicular cancer in male offspring: A systematic review and meta-analysis SO CANCER EPIDEMIOLOGY LA English DT Review DE Epidemiology; Maternal; Meta-analysis; Obesity; Pregnancy; Review; Systematic; Testicular neoplasms ID GERM-CELL CANCER; ESTROGEN EXPOSURE; BIRTH-ORDER; PARITY; PREGNANCY; WEIGHT; COHORT; AGE; CRYPTORCHIDISM; DISORDERS AB Objectives: To date a number of studies have examined the association between maternal weight and testicular cancer risk although results have been largely inconsistent. This systematic review and meta-analysis investigated the nature of this association. Methods: Search strategies were conducted in Ovid Medline (1950-2009), Embase (1980-2009), Web of Science (1970-2009), and CINAHL (1937-2009) using keywords for maternal weight (BMI) and testicular cancer. Results: The literature search produced 1689 hits from which 63 papers were extracted. Only 7 studies met the pre-defined criteria. Random effects meta-analyses were conducted. The combined unadjusted OR (95% Cl) of testicular cancer in the highest reported category of maternal BMI compared with the moderate maternal BMI was 0.82 (0.65-1.02). The Cochran's Q P value was 0.82 and the corresponding I(2) was 0%, both indicating very little variability among studies. The combined unadjusted OR (95% Cl) for testicular cancer risk in the lowest reported category of maternal BMI compared to a moderate maternal BMI category was 0.88 (0.65-1.20). The Cochran's Q P value was 0.05 and the corresponding I(2) was 54%, indicating evidence of statistical heterogeneity. The combined unadjusted OR (95% Cl) of testicular cancer risk per unit increase in maternal BMI was 1.01 (0.97-1.06). The Cochran's Q test had a P value of 0.05 and the corresponding I(2) was 55% indicating evidence of statistical heterogeneity. Conclusion: This meta-analysis, which included a small number of studies, showed that a higher maternal weight does not increase the risk of testicular cancer in male offspring. Though an inverse association between high maternal BMI and testicular cancer risk was detected, it was not statistically significant. Further primary studies with adjustment for appropriate confounders are required. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Alam, Shama S.; Cantwell, Marie M.; Cardwell, Chris R.; Murray, Liam J.] Queens Univ Belfast, Ctr Publ Hlth, Canc Epidemiol & Hlth Serv Res Grp, Belfast BT12 6BA, Antrim, North Ireland. [Cook, Michael B.] NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Alam, SS (reprint author), Queens Univ Belfast, Ctr Publ Hlth, Canc Epidemiol & Hlth Serv Res Grp, Grosvenor Rd, Belfast BT12 6BA, Antrim, North Ireland. EM salam01@qub.ac.uk RI Cook, Michael/A-5641-2009; OI Cook, Michael/0000-0002-0533-7302; Cardwell, Chris/0000-0002-2689-4335 FU Intramural NIH HHS [Z99 CA999999, NIH0013132602] NR 44 TC 3 Z9 4 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1877-7821 J9 CANCER EPIDEMIOL JI Cancer Epidemiol. PD OCT PY 2010 VL 34 IS 5 BP 509 EP 515 DI 10.1016/j.canep.2010.07.006 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 677FO UT WOS:000283974700001 PM 20800565 ER PT J AU Kabat, GC Park, Y Hollenbeck, AR Schatzkin, A Rohan, TE AF Kabat, Geoffrey C. Park, Yikyung Hollenbeck, Albert R. Schatzkin, Arthur Rohan, Thomas E. TI Intake of fruits and vegetables, and risk of endometrial cancer in the NIH-AARP Diet and Health Study SO CANCER EPIDEMIOLOGY LA English DT Article DE Fruit and vegetable intake; Endometrial cancer; Phytochemicals; Cohort studies ID FOOD-FREQUENCY QUESTIONNAIRE; RETIRED-PERSONS DIET; NATIONAL-INSTITUTES; UNITED-STATES; AMERICAN-ASSOCIATION; PROBLEMATIC ASPECTS; PHYSICAL-ACTIVITY; UTERINE CORPUS; CONSUMPTION; MECHANISMS AB Background: Fruits and vegetables contain a wide variety of phytochemicals which may have anti-carcinogenic effects. Although the results of case-control studies have suggested a possible protective effect of fruit and vegetable intake on the risk of endometrial carcinoma, few cohort studies have examined this association. Materials and methods: We used data from the NIH-AARP Diet and Health Study to assess the association of fruit and vegetable consumption, as well as intake of specific botanical groupings of fruits and vegetables, with endometrial cancer risk among 112,088 women who completed a food-frequency questionnaire at baseline, in 1995-1996. During 8 years of follow-up 1142 incident cases of endometrial cancer were ascertained. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (95% Cl). Results: After adjustment for covariates, HRs for the highest compared to the lowest quintile of total fruit and total vegetable intake were 1.30 (95% Cl 1.04-1.61, P for trend 0.05) and 1.09 (95% Cl 0.90-1.33, P for trend 0.55), respectively. No inverse associations were observed for intake of any of 13 botanical groupings of fruits and vegetables. Conclusions: Results from this large prospective study do not support a protective role of a high intake of fruits or vegetables on the risk of endometrial cancer in older women. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Kabat, Geoffrey C.; Rohan, Thomas E.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10461 USA. [Park, Yikyung; Schatzkin, Arthur] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20801 USA. [Hollenbeck, Albert R.] AARP, Washington, DC 20049 USA. RP Kabat, GC (reprint author), Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, 1300 Morris Pk Ave, Bronx, NY 10461 USA. EM Geoffrey.kabat@einstein.yu.edu; parkyik@mail.nih.gov; ahollenbeck@aarp.org; Schatzka@exchange.nih.gov; Thomas.rohan@einstein.yu.edu OI Park, Yikyung/0000-0002-6281-489X FU Intramural NIH HHS [ZIA CP010196-05] NR 50 TC 7 Z9 7 U1 1 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1877-7821 J9 CANCER EPIDEMIOL JI Cancer Epidemiol. PD OCT PY 2010 VL 34 IS 5 BP 568 EP 573 DI 10.1016/j.canep.2010.06.005 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 677FO UT WOS:000283974700009 PM 20619761 ER PT J AU Gaudet, MM Falk, RT Gierach, GL Lacey, JV Graubard, BI Dorgan, JF Brinton, LA AF Gaudet, Mia M. Falk, Roni T. Gierach, Gretchen L. Lacey, James V., Jr. Graubard, Barry I. Dorgan, Joanne F. Brinton, Louise A. TI Do adipokines underlie the association between known risk factors and breast cancer among a cohort of United States women? SO CANCER EPIDEMIOLOGY LA English DT Article DE Breast cancer; Adipokines; Obesity; Biomarkers; Epidemiology ID ADIPOSE-TISSUE; PLASMINOGEN-ACTIVATOR; SERUM ADIPONECTIN; METABOLIC SYNDROME; RESISTIN LEVELS; CELLS; ESTROGEN; RELEASE; FAT AB Introduction: Obesity is a well-established risk factor for postmenopausal breast cancer, but mechanisms underlying the association are unclear. Adipocyte-derived, cytokine-like adipokines have been suggested as contributory factors. To evaluate their association with breast cancer risk factors and breast cancer risk, we conducted a nested case-control study of 234 postmenopausal breast cancer cases and 234 controls in a cohort of U.S. women with prospectively-collected serum samples obtained in the mid 1970s and followed for up to 25 years. Methods: Adiponectin, absolute plasminogen activator inhibitor-1 (aPAI-1), and resistin were measured by a multiplex immunoassay. Sex hormones were available for 67 cases and 67 controls. Results: Among controls, we found that lower levels of adiponectin and higher levels of aPAI-1 were correlated with increasing levels of estradiol (Spearman r = 0.26, p-value = 0.033; r = 0.42, p = 0.0003), decreasing levels of sex hormone binding globulin (r = 0.38, p = 0.0013; r = 0.32, p = 0.0076), and increasing body mass index (BMI) (r = 0.31, p = <0.0001: r = 0.39, p = <0.0001). Hormones were not associated with resistin. Among the relatively small percentage of women using postmenopausal hormones at the time of blood collection (13.7%), aPAI-1 levels were higher than in non-users (p = 0.0054). Breast cancer risk was not associated with circulating levels of adiponectin (age-adjusted p for linear trend = 0.43), aPAI-1 (p = 0.78), or resistin (p = 0.91). The association was not confounded by BMI, parity, age at first full-term birth, age at menopause, current postmenopausal hormone use, and circulating sex steroid hormones. Furthermore, adipokine associations were not modified by BMI (p > 0.05). The lack of association with risk may be due to measurement error of the laboratory assays. Discussion: lower levels of adiponectin and higher levels of aPAI-1 measured in prospectively-collected serum from postmenopausal women were associated with increasing BMI but not breast cancer risk. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Gaudet, Mia M.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. [Falk, Roni T.; Gierach, Gretchen L.; Lacey, James V., Jr.; Graubard, Barry I.; Brinton, Louise A.] NCI, Div Canc Epidemiol & Biostat, Rockville, MD USA. [Dorgan, Joanne F.] Fox Chase Canc Ctr, Div Populat Sci, Philadelphia, PA 19111 USA. RP Gaudet, MM (reprint author), 307 E 63th St,3rd Floor, New York, NY 10021 USA. EM mia.gaudet@einstein.yu.edu RI Brinton, Louise/G-7486-2015; Gierach, Gretchen/E-1817-2016 OI Brinton, Louise/0000-0003-3853-8562; Gierach, Gretchen/0000-0002-0165-5522 FU Intramural NIH HHS [ZIA CP010126-14] NR 26 TC 25 Z9 26 U1 1 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1877-7821 J9 CANCER EPIDEMIOL JI Cancer Epidemiol. PD OCT PY 2010 VL 34 IS 5 BP 580 EP 586 DI 10.1016/j.canep.2010.05.014 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 677FO UT WOS:000283974700011 PM 20579950 ER PT J AU Graubard, BI Freedman, AN Gail, MH AF Graubard, Barry I. Freedman, Andrew N. Gail, Mitchell H. TI Five-Year and Lifetime Risk of Breast Cancer among U.S. Subpopulations: Implications for Magnetic Resonance Imaging Screening SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID FAMILY-HISTORY; SOCIETY GUIDELINES; ASSESSMENT MODELS; GAIL MODEL; WOMEN; PREDICTION; VALIDATION; MRI AB Background: Guidelines from the American Cancer Society recommend annual breast magnetic resonance imaging (MRI) screening for women with a projected lifetime risk of >= 20% based on risk models that use family history. Because MRI screening is costly and has limited specificity, estimates of the numbers of U. S. women with >= 20% breast cancer risk would be useful. Methods: We used data from the 2000 and 2005 National Health Interview Survey and the National Cancer Institute (NCI) Breast Cancer Risk Assessment Tool (i.e., Gail model 2 with a revision for African Americans) to calculate estimates of U. S. women by age and race/ethnicity categories with a lifetime absolute breast cancer risk of >= 20%. Distributions of 5-year and lifetime absolute risk of breast cancer were compared across demographic groups. Results: We estimated that 1.09% (95% confidence interval, 0.95-1.24%) of women age 30 to 84 years have a lifetime absolute breast cancer risk of >= 20%, which translates to 880,063 U. S. women eligible for MRI screening. The 5-year risks are highest for white non-Hispanics and lowest for Hispanics. The lifetime risks decrease with age and are generally highest for white non-Hispanics, lower for African American non-Hispanic, and lowest for Hispanics. Conclusion: We provide national estimates of the number of U. S. women who would be eligible for MRI breast screening and distributions of 5-year and lifetime risks of breast cancer using the NCI Breast Cancer Risk Assessment Tool. Impact: These estimates inform the potential resources and public health demand for MRI screening and chemopreventive interventions that might be required for U. S. women. Cancer Epidemiol Biomarkers Prev; 19(10); 2430-6. (C) 2010 AACR. C1 [Graubard, Barry I.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Freedman, Andrew N.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Graubard, BI (reprint author), NCI, Biostat Branch, Div Canc Epidemiol & Genet, Execut Plaza S Room 8024,6120 Execut Blvd, Bethesda, MD 20892 USA. EM graubarb@mail.nih.gov NR 30 TC 12 Z9 12 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 OCT PY 2010 VL 19 IS 10 BP 2430 EP 2436 DI 10.1158/1055-9965.EPI-10-0324 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 659TT UT WOS:000282590500003 PM 20841391 ER PT J AU Woditschka, S Habel, LA Udaltsova, N Friedman, GD Sieh, W AF Woditschka, Stephan Habel, Laurel A. Udaltsova, Natalia Friedman, Gary D. Sieh, Weiva TI Lipophilic Statin Use and Risk of Breast Cancer Subtypes SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID PROGESTERONE-RECEPTOR STATUS; COLLABORATIVE REANALYSIS; METAANALYSIS; ESTROGEN; EXPRESSION; LOVASTATIN; MAMMARY; GROWTH; PREVENTION; DATABASE AB Background/Aims: Statins are widely used and of high interest as potential chemopreventive agents for cancer. Preclinical studies suggest that lipophilic statins have anticancer properties targeting hormone receptor (HR)-negative breast cancer. Few epidemiologic studies have investigated the relationship between lipophilic statin use and risk for breast cancer, stratified by HR status. We conducted a large case-control study within Kaiser Permanente of Northern California (KPNC) to determine whether chronic use of lipophilic statins is associated with decreased risk of HR-negative breast cancer or other breast cancer subtypes. Methods: We identified 22,488 breast cancer cases diagnosed from 1997 to 2007, and 224,860 controls matched to cases based upon birth year and duration of KPNC pharmacy coverage. Use of lipophilic statins was ascertained using the comprehensive electronic pharmacy records of KPNC. Results: We found no association between lipophilic statin use (>= 2 y versus never) and overall breast cancer risk (odds ratio(adj), 1.02; 95% CI, 0.97-1.08) in conditional logistic regression models adjusted for oral contraceptive and hormone therapy use. Women who used lipophilic statins did not have a decreased risk of HR-negative breast cancer (odds ratio(adj), 0.98; 95% CI, 0.84-1.14) nor altered risk of HR-positive disease (odds ratio(adj), 1.03; 95% CI, 0.97-1.10). Furthermore, lipophilic statin use was not associated with risk of any of the intrinsic subtypes, luminal A, luminal B, human epidermal growth factor receptor 2 positive/estrogen receptor negative, or triple negative. Conclusions: Our results do not support an association of lipophilic statin use with the risk for breast cancer in general or with risks of HR-negative or other breast cancer subtypes specifically. Impact: These findings do not confirm previous reports of a possible preventive association. Cancer Epidemiol Biomarkers Prev; 19(10); 2479-87. (c) 2010 AACR. C1 [Habel, Laurel A.; Udaltsova, Natalia; Friedman, Gary D.] Kaiser Permanente Med Care Program, Div Res, Oakland, CA 94612 USA. [Woditschka, Stephan] NCI, Canc Prevent Fellowship Program, NIH, Bethesda, MD 20892 USA. [Woditschka, Stephan; Habel, Laurel A.; Friedman, Gary D.; Sieh, Weiva] Stanford Univ Sch Med, Dept Hlth Res & Policy, Stanford, CA USA. RP Habel, LA (reprint author), Kaiser Permanente Med Care Program, Div Res, 2000 Broadway, Oakland, CA 94612 USA. EM lah@dor.kaiser.org FU Kaiser Foundation Research Institute; University of North Carolina from Sanofi-Aventis; Genomic Health, Inc.; Bio Theranostics through the Kaiser Foundation Research Institute; Genentech through the Kaiser Foundation Research Institute; Merck through the Kaiser Foundation Research Institute; National Cancer Institute [R01 CA 098838]; Office of the Director, National Cancer Institute FX L.A. Habel is about to receive a research grant through the Kaiser Foundation Research Institute and the University of North Carolina from Sanofi-Aventis to examine risk for breast and other cancers associated with medications used to treat diabetes and has research grants from Genomic Health, Inc., and Bio Theranostics through the Kaiser Foundation Research Institute to examine gene expression profiles and breast cancer outcomes, from Genentech through the Kaiser Foundation Research Institute to examine patient and tumor factors associated with HER2 status, and from Merck through the Kaiser Foundation Research Institute to examine risk for herpes zoster among cancer patients.; Grant R01 CA 098838 from the National Cancer Institute, (L.A. Habel, G. D. Friedman), and support from the Cancer Prevention Fellowship Program, Office of the Director, National Cancer Institute (S. Woditschka). NR 40 TC 15 Z9 15 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 OCT PY 2010 VL 19 IS 10 BP 2479 EP 2487 DI 10.1158/1055-9965.EPI-10-0524 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 659TT UT WOS:000282590500009 PM 20729289 ER PT J AU Lam, TK Ruczinski, I Helzlsouer, KJ Shugart, YY Caulfield, LE Alberg, AJ AF Lam, Tram Kim Ruczinski, Ingo Helzlsouer, Kathy J. Shugart, Yin Yao Caulfield, Laura E. Alberg, Anthony J. TI Cruciferous Vegetable Intake and Lung Cancer Risk: A Nested Case-Control Study Matched on Cigarette Smoking SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID S-TRANSFERASE POLYMORPHISMS; DIETARY ISOTHIOCYANATES; BETA-CAROTENE; SULFORAPHANE; CONSUMPTION; SMOKERS; FRUIT; QUESTIONNAIRES; ANTIOXIDANTS; PERSPECTIVE AB Background: Due predominantly to cigarette smoking, lung cancer is the leading cancer-related cause of death worldwide. Cruciferous vegetables may reduce lung cancer risk. The association between intake of cruciferous vegetables and lung cancer risk was investigated in the CLUE II study, a community-based cohort established in 1989. Methods: We matched 274 incident cases of lung cancer diagnosed from 1990 to 2005 to 1,089 cancer-free controls on age, sex, and cigarette smoking. Dietary information was collected at baseline. Multivariable odds ratios (OR) and 95% confidence intervals (95% CI) were calculated using conditional logistic regression. Results: Intake of cruciferous vegetables was inversely associated with lung cancer risk (highest-versus-lowest fourth: OR(Q4vsQ1), 0.57; 95% CI, 0.38-0.85; P-trend = 0.01). The inverse associations held true for former smokers (OR(Q4vsQ1), 0.49; 95% CI, 0.27-0.92; P-trend = 0.05) and current smokers (OR(Q4vsQ1), 0.52; 95% CI, 0.29-0.95; P-trend = 0.02). Conclusions: After carefully controlling for cigarette smoking, higher intake of cruciferous vegetable was associated with lower risk of lung cancer. Impact: The observed inverse association coupled with accumulating evidence suggests that intake of cruciferous vegetables is inversely associated with lung cancer risk, and this association seems to hold true beyond the confounding effects of cigarette smoking. Cancer Epidemiol Biomarkers Prev; 19(10); 2534-40. (C) 2010 AACR. C1 [Alberg, Anthony J.] Med Univ S Carolina, Hollings Canc Ctr, Charleston, SC 29425 USA. [Alberg, Anthony J.] Med Univ S Carolina, Dept Med, Div Biostat & Epidemiol, Charleston, SC 29425 USA. [Lam, Tram Kim; Helzlsouer, Kathy J.; Alberg, Anthony J.] Johns Hopkins Univ Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Ruczinski, Ingo] Johns Hopkins Univ Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA. [Caulfield, Laura E.] Johns Hopkins Univ Bloomberg Sch Publ Hlth, Ctr Human Nutr, Dept Int Hlth, Baltimore, MD USA. [Helzlsouer, Kathy J.] Mercy Med Ctr, Baltimore, MD USA. [Lam, Tram Kim] NCI, Canc Prevent Fellowship Program, Off Prevent Oncol, Canc Prevent Div, Rockville, MD USA. [Lam, Tram Kim] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Shugart, Yin Yao] NIMH, Genom Res Branch, Div Neurosci & Basic Behav Sci, NIH, Bethesda, MD 20892 USA. [Helzlsouer, Kathy J.] George W Comstock Ctr Publ Hlth Res & Prevent, Hagerstown, MD USA. RP Alberg, AJ (reprint author), Med Univ S Carolina, Hollings Canc Ctr, 86 Jonathan Lucas St,POB 250955, Charleston, SC 29425 USA. EM alberg@musc.edu FU Institutional Research Epidemiology Fellowship [T32CA009314]; National Institute of Aging [5U01AG018033]; National Cancer Institute [CA105069] FX Institutional Research Epidemiology Fellowship grant T32CA009314, National Institute of Aging grant 5U01AG018033, and National Cancer Institute grant CA105069. This report is based, at least in part, on information provided by the Maryland Cancer Registry, Maryland Department of Health and Mental Health. NR 39 TC 20 Z9 21 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 OCT PY 2010 VL 19 IS 10 BP 2534 EP 2540 DI 10.1158/1055-9965.EPI-10-0475 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 659TT UT WOS:000282590500015 PM 20841387 ER PT J AU Tsai, HT Cross, AJ Graubard, BI Oken, M Schatzkin, A Caporaso, NE AF Tsai, Huei-Ting Cross, Amanda J. Graubard, Barry I. Oken, Martin Schatzkin, Arthur Caporaso, Neil E. TI Dietary Factors and Risk of Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma: A Pooled Analysis of Two Prospective Studies SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID NON-HODGKIN-LYMPHOMA; DESIGN; WOMEN AB Background: Other than male sex, family history, advanced age, and race, risk factors for chronic lymphocytic leukemia and small lymphocytic lymphoma (CLL/SLL) are unknown. Very few studies have investigated diet in relation to these leukemias, and no consistent associations are known. Methods: Using two large prospective population-based studies, we evaluated the relationship between diet and CLL/SLL risk. Among 525,982 men and women free of cancer at enrollment, we identified 1,129 incident CLL/SLL cases during 11.2 years of follow-up. Results: We found no associations between total fat, saturated fat, fiber, red meat, processed meat, fruit, or vegetable intake and risk of CLL/SLL. We noted a suggestive positive association between body mass index and CLL/SLL (hazard ratio, 1.30; 95% confidence interval, 0.99-1.36). Conclusion: We did not find any associations between food or nutrient intake and CLL/SLL. Impact: Our large prospective study indicates that diet may not play a role in CLL/SLL development. Cancer Epidemiol Biomarkers Prev; 19(10); 2680-4. (C) 2010 AACR. C1 [Caporaso, Neil E.] NCI, Pharmacogenet Sect, Genet Epidemiol Branch, Div Canc Epidemiol & Genet,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Tsai, Huei-Ting] Georgetown Univ, Med Ctr, Canc Control Program, Washington, DC 20007 USA. [Oken, Martin] Univ Minnesota, Div Hematol Oncol & Transplantat, Minneapolis, MN USA. RP Caporaso, NE (reprint author), NCI, Pharmacogenet Sect, Genet Epidemiol Branch, Div Canc Epidemiol & Genet,Dept Hlth & Human Serv, EPS 7002,6120 Execut Blvd, Bethesda, MD 20892 USA. EM caporaso@nih.gov FU Intramural NIH HHS [Z01 CP010152-08] NR 9 TC 12 Z9 12 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD OCT PY 2010 VL 19 IS 10 BP 2680 EP 2684 DI 10.1158/1055-9965.EPI-10-0585 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 659TT UT WOS:000282590500032 PM 20929883 ER PT J AU Goff, SL Johnson, LA Black, MA Xu, H Zheng, ZL Cohen, CJ Morgan, RA Rosenberg, SA Feldman, SA AF Goff, Stephanie L. Johnson, Laura A. Black, Mary A. Xu, Hui Zheng, Zhili Cohen, Cyrille J. Morgan, Richard A. Rosenberg, Steven A. Feldman, Steven A. TI Enhanced receptor expression and in vitro effector function of a murine-human hybrid MART-1-reactive T cell receptor following a rapid expansion SO CANCER IMMUNOLOGY IMMUNOTHERAPY LA English DT Article DE Melanoma; MART-1; T cell receptor; Retrovirus; Gene therapy; Immunotherapy ID METASTATIC MELANOMA; CANCER REGRESSION; GENE-TRANSFER; ADOPTIVE IMMUNOTHERAPY; ENGINEERED LYMPHOCYTES; ANTITUMOR-ACTIVITY; REACTIVE TCR; TUMOR; ANTIGEN; RECOGNITION AB Peripheral blood lymphocytes (PBL) genetically modified to express T cell receptors (TCR) specific to known melanoma antigens, such as melanoma antigen recognized by T cells-1 (MART-1), and gp100 can elicit objective tumor regression when administered to patients with metastatic melanoma. It has also been demonstrated that modifications within the constant regions of a fully human TCR can enhance surface expression and stability without altering antigen specificity. In this study, we evaluated the substitution of murine constant regions for their human counterpart within the DMF5 MART-1-specific TCR. Unlike previous studies, all modified TCRs were inserted into retroviral vectors and analyzed for expression and function following a clinical transduction protocol. PBL were transduced with retroviral supernatant generated from stable packaging lines encoding melanoma-specific TCRs. This protocol resulted in high levels of antigen-specific T cells without the need for additional peptide stimulation and selection. Both the human and murinized TCR efficiently transduced PBL; however, the murinized TCR exhibited significantly higher tetramer binding, mean fluorescence intensity, as well as, increased in vitro effector function following our clinical transduction and expansion protocol. Additional TCR modifications including insertion of a second disulfide bond or the linker modifications evaluated herein did not significantly enhance TCR expression or subsequent in vitro effector function. We conclude that the substitution of a human constant region with a murine constant region was sufficient to increase receptor expression and tetramer binding as well as antitumor activity of the DMF5 TCR and could be a tool to augment other antigen-specific TCR. C1 [Goff, Stephanie L.; Johnson, Laura A.; Black, Mary A.; Xu, Hui; Zheng, Zhili; Cohen, Cyrille J.; Morgan, Richard A.; Rosenberg, Steven A.; Feldman, Steven A.] NCI, Surg Branch, NIH, ACRF, Bethesda, MD 20892 USA. RP Feldman, SA (reprint author), NCI, Surg Branch, NIH, ACRF, 1B37A,10 Ctr Dr, Bethesda, MD 20892 USA. EM feldmanst@mail.nih.gov RI Johnson, Laura/H-4861-2013 FU Intramural NIH HHS [ZIC BC010989-02] NR 30 TC 14 Z9 15 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-7004 J9 CANCER IMMUNOL IMMUN JI Cancer Immunol. Immunother. PD OCT PY 2010 VL 59 IS 10 BP 1551 EP 1560 DI 10.1007/s00262-010-0882-5 PG 10 WC Oncology; Immunology SC Oncology; Immunology GA 630FM UT WOS:000280258500011 PM 20628878 ER PT J AU Harris, PJ Takebe, N Ivy, SP AF Harris, Pamela Jo Takebe, Naoko Ivy, S. Percy TI Molecular Conversations and the Development of the Hair Follicle and Basal Cell Carcinoma SO CANCER PREVENTION RESEARCH LA English DT Review ID SONIC-HEDGEHOG; STEM-CELLS; SIGNALING PATHWAY; BETA-CATENIN; EXPRESSION; CYCLE; SKIN; EPIDERMIS; GENES; TUMORIGENESIS AB The understanding of the anatomy and development of fetal and adult hair follicles and the molecular study of the major embryonic pathways that regulate the hair follicle have led to exciting discoveries concerning the development of basal cell carcinoma (BCC). These studies have shed light on the major roles of Sonic hedgehog (Shh) signaling and its interactions with the insulin-like growth factor (IGF) axis in BCC development. New work, for example, explores a link between Shh signaling and IGF binding protein-2 (IGFBP-2) in the hair follicle as it transforms into BCC. IGFBP-2 was overexpressed in specific hair follicle cells of mice with ectopically activated Shh signaling [keratin 14 (K14)-Cre: patched homologue 1 (Cre: Ptch1)(lox/lox) mice]. Ptch1 deletion resulted in both an expansion of the stem cell niche and inhibition of cell differentiation. In transformed hair follicles, IGFBP-2 mediates epidermal progenitor cell expansion. Evidence also indicated that IGFBP-2 is expressed in human BCC. Cancer Prev Res; 3(10); 1217-21. (c) 2010 AACR. C1 [Harris, Pamela Jo; Takebe, Naoko; Ivy, S. Percy] NCI, Canc Therapy Evaluat Program, NIH, Bethesda, MD 20892 USA. RP Ivy, SP (reprint author), NCI, Canc Therapy Evaluat Program, NIH, 6130 Execut Plaza N,Suite 7131, Bethesda, MD 20892 USA. EM ivyp@ctep.nci.nih.gov NR 31 TC 8 Z9 9 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 J9 CANCER PREV RES JI Cancer Prev. Res. PD OCT PY 2010 VL 3 IS 10 BP 1217 EP 1221 DI 10.1158/1940-6207.CAPR-10-0210 PG 5 WC Oncology SC Oncology GA 658TC UT WOS:000282511300002 PM 20858758 ER PT J AU Chen, M Hildebrandt, MAT Clague, J Kamat, AM Picornell, A Chang, J Zhang, XF Izzo, J Yang, HS Lin, J Gu, JA Chanock, S Kogevinas, M Rothman, N Silverman, DT Garcia-Closas, M Grossman, HB Dinney, CP Malats, N Wu, XF AF Chen, Meng Hildebrandt, Michelle A. T. Clague, Jessica Kamat, Ashish M. Picornell, Antoni Chang, Joshua Zhang, Xiaofan Izzo, Julie Yang, Hushan Lin, Jie Gu, Jian Chanock, Stephen Kogevinas, Manolis Rothman, Nathaniel Silverman, Debra T. Garcia-Closas, Montserrat Grossman, H. Barton Dinney, Colin P. Malats, Nuria Wu, Xifeng TI Genetic Variations in the Sonic Hedgehog Pathway Affect Clinical Outcomes in Non-Muscle-Invasive Bladder Cancer SO CANCER PREVENTION RESEARCH LA English DT Article ID TRANSITIONAL-CELL CARCINOMA; CALMETTE-GUERIN IMMUNOTHERAPY; FALSE DISCOVERY RATES; STEM-CELLS; BCG IMMUNOTHERAPY; PANCREATIC-CANCER; SIGNALING PATHWAY; IN-SITU; RECURRENCE; ACTIVATION AB Sonic hedgehog (Shh) pathway genetic variations may affect bladder cancer risk and clinical outcomes. Therefore, we genotyped 177 single-nucleotide polymorphisms (SNP) in 11 Shh pathway genes in a study including 803 bladder cancer cases and 803 controls. We assessed SNP associations with cancer risk and clinical outcomes in 419 cases of non-muscle-invasive bladder cancer (NMIBC) and 318 cases of muscle-invasive and metastatic bladder cancer (MiMBC). Only three SNPs (GLI3 rs3823720, rs3735361, and rs10951671) reached nominal significance in association with risk (P <= 0.05), which became nonsignificant after adjusting for multiple comparisons. Nine SNPs reached a nominally significant individual association with recurrence of NMIBC in patients who received transurethral resection (TUR) only (P <= 0.05), of which two (SHH rs1233560 and GLI2 rs11685068) were replicated independently in 356 TUR-only NMIBC patients, with P values of 1.0 x 10(-3) (SHH rs1233560) and 1.3 x 10(-3) (GLI2 rs11685068). Nine SNPs also reached a nominally significant individual association with clinical outcome of NMIBC patients who received Bacillus Calmette-Guerin (BCG; P <= 0.05), of which two, the independent GLI3 variants rs6463089 and rs3801192, remained significant after adjusting for multiple comparisons (P = 2 x 10(-4) and 9 x 10(-4), respectively). The wildtype genotype of either of these SNPs was associated with a lower recurrence rate and longer recurrence-free survival (versus the variants). Although three SNPs (GLI2 rs735557, GLI2 rs4848632, and SHH rs208684) showed nominal significance in association with overall survival in MiMBC patients (P <= 0.05), none remained significant after multiple-comparison adjustments. Germ-line genetic variations in the Shh pathway predicted clinical outcomes of TUR and BCG for NMIBC patients. Cancer Prev Res; 3(10); 1235-45. (c) 2010 AACR. C1 [Wu, Xifeng] Univ Texas MD Anderson Canc Ctr, Unit 1340, Dept Epidemiol, Houston, TX 77030 USA. [Kamat, Ashish M.; Grossman, H. Barton; Dinney, Colin P.] Univ Texas MD Anderson Canc Ctr, Dept Urol, Houston, TX 77030 USA. [Izzo, Julie] Univ Texas MD Anderson Canc Ctr, Dept Expt Therapeut, Houston, TX 77030 USA. [Picornell, Antoni; Malats, Nuria] Spanish Natl Canc Res Ctr, Genet & Mol Epidemiol Grp, Madrid, Spain. [Chanock, Stephen; Rothman, Nathaniel; Silverman, Debra T.; Garcia-Closas, Montserrat] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Kogevinas, Manolis] Ctr Res Environm Epidemiol CREAL, Barcelona, Spain. [Kogevinas, Manolis] Municipal Inst Med Res, Barcelona, Spain. [Kogevinas, Manolis] CIBERESP, Barcelona, Spain. [Kogevinas, Manolis] Natl Sch Publ Hlth, Athens, Greece. RP Wu, XF (reprint author), Univ Texas MD Anderson Canc Ctr, Unit 1340, Dept Epidemiol, 1155 Pressler Blvd, Houston, TX 77030 USA. EM xwu@mdanderson.org RI Garcia-Closas, Montserrat /F-3871-2015; Malats, Nuria/H-7041-2015; Kogevinas, Manolis/C-3918-2017 OI Garcia-Closas, Montserrat /0000-0003-1033-2650; Malats, Nuria/0000-0003-2538-3784; FU NIH [U01 CA 127615, R01 CA 74880, P50 CA 91846, R01 CA 131335] FX NIH grants U01 CA 127615, R01 CA 74880, P50 CA 91846, and R01 CA 131335. NR 60 TC 26 Z9 26 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 EI 1940-6215 J9 CANCER PREV RES JI Cancer Prev. Res. PD OCT PY 2010 VL 3 IS 10 BP 1235 EP 1245 DI 10.1158/1940-6207.CAPR-10-0035 PG 11 WC Oncology SC Oncology GA 658TC UT WOS:000282511300004 PM 20858759 ER PT J AU Yu, W Cline, M Maxwell, LG Berrigan, D Rodriguez, G Warri, A Hilakivi-Clarke, L AF Yu, Wei Cline, Mark Maxwell, Larry G. Berrigan, David Rodriguez, Gustavo Warri, Anni Hilakivi-Clarke, Leena TI Dietary Vitamin D Exposure Prevents Obesity-Induced Increase in Endometrial Cancer in Pten(+/-) Mice SO CANCER PREVENTION RESEARCH LA English DT Article ID ESTROGEN-RECEPTOR-ALPHA; BETA ER-BETA; BREAST-CANCER; GENE-EXPRESSION; INSULIN HYPERSENSITIVITY; RELATIVE EXPRESSION; BODY-COMPOSITION; ADIPOSE-TISSUE; MUTANT MICE; PTEN AB The possibility that dietary vitamin D-3 (VD3) exposure inhibits endometrial carcinogenesis in an animal model and modifies the enhanced risk of endometrial carcinoma associated with obesity was investigated. At 4 weeks of age, Pten(+/-) and wild-type mice were each divided into four treatment groups and fed AIN93G control diet, or AIN93G-based diet containing either 25,000 international units of VD3 per kilogram of diet, 58% fat to induce obesity (high fat), or high fat and 25,000 international units of VD3 per kilogram of diet. Mice were kept on these diets until they were sacrificed at week 28. Although VD3 did not affect endometrial cancer risk, it inhibited obesity-induced increase in endometrial lesions. Specifically, high-fat diet increased focal glandular hyperplasia with atypia and malignant lesions from 58% in the control diet-fed Pten(+/-) mice to 78% in obese mice. Dietary VD3 decreased the incidence of endometrial pathology in obese Pten(+/-) mice to 25% (P < 0.001). VD3 altered the endometrial expression of 25-hydroxylase, 1 alpha-hydroxylase, and vitamin D receptor in the wild-type and Pten(+/-) mice. Estrogen receptor-a mRNA levels were higher (P < 0.014) and progesterone receptor protein levels in the luminal epithelium were lower (P < 0.04) in the endometrium of control diet-fed Pten(+/-) than wild-type mice, but the expression of these receptors was not affected by the dietary exposures. VD3 reversed the obesity-induced increase in osteopontin (P < 0.001) and significantly increased E-cadherin expression (P < 0.019) in the endometrium of obese Pten(+/-) mice. Our data confirm the known association between obesity and endometrial cancer risk. Dietary exposure to VD3 inhibited the carcinogenic effect of obesity on the endometrium. This protective effect was linked to a reduction in the expression of osteopontin and increase in E-cadherin. Cancer Prev Res; 3(10); 1246-58. (c) 2010 AACR. C1 [Yu, Wei; Warri, Anni; Hilakivi-Clarke, Leena] Georgetown Univ, Dept Oncol, Washington, DC 20057 USA. [Maxwell, Larry G.] Gynecol Dis Ctr, Integrated Div Gynecol Oncol, Washington, DC USA. [Cline, Mark] Wake Forest Univ, Sch Med, Dept Pathol Comparat Med, Winston Salem, NC 27109 USA. [Berrigan, David] NCI, Bethesda, MD 20892 USA. [Rodriguez, Gustavo] Northwestern Univ, NorthShore Univ Hlth Syst, Div Gynecol Oncol, Chicago, IL 60611 USA. RP Hilakivi-Clarke, L (reprint author), Georgetown Univ, Dept Oncol, Res Bldg,Room E407,3970 Reservoir Rd NW, Washington, DC 20057 USA. EM clarkel@georgetown.edu FU National Cancer Institute [U54 CA100970]; Department of Defense Telemedicine and Advanced Technology Center [W81XWH-05-2-0005] FX National Cancer Institute (U54 CA100970) and the Department of Defense Telemedicine and Advanced Technology Center, Award Number W81XWH-05-2-0005. The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of Defense. NR 67 TC 6 Z9 7 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 J9 CANCER PREV RES JI Cancer Prev. Res. PD OCT PY 2010 VL 3 IS 10 BP 1246 EP 1258 DI 10.1158/1940-6207.CAPR-10-0088 PG 13 WC Oncology SC Oncology GA 658TC UT WOS:000282511300005 PM 20858763 ER PT J AU Fabian, CJ Kimler, BF Zalles, CM Klemp, JR Petroff, BK Khan, QJ Sharma, P Setchell, KDR Zhao, XH Phillips, TA Metheny, T Hughes, JR Yeh, HW Johnson, KA AF Fabian, Carol J. Kimler, Bruce F. Zalles, Carola M. Klemp, Jennifer R. Petroff, Brian K. Khan, Qamar J. Sharma, Priyanka Setchell, Kenneth D. R. Zhao, Xueheng Phillips, Teresa A. Metheny, Trina Hughes, Jennifer R. Yeh, Hung-Wen Johnson, Karen A. TI Reduction in Ki-67 in Benign Breast Tissue of High-Risk Women with the Lignan Secoisolariciresinol Diglycoside SO CANCER PREVENTION RESEARCH LA English DT Article ID FINE-NEEDLE-ASPIRATION; DIETARY PHYTOESTROGEN INTAKE; ESTROGEN-RECEPTOR STATUS; SERUM ENTEROLACTONE CONCENTRATION; CANCER RISK; POSTMENOPAUSAL WOMEN; MAMMALIAN LIGNANS; GROWTH-FACTOR; MAMMOGRAPHIC DENSITIES; PROLIFERATIVE ACTIVITY AB Preclinical and correlative studies suggest reduced breast cancer with higher lignan intake or blood levels. We conducted a pilot study of modulation of risk biomarkers for breast cancer in premenopausal women after administration of the plant lignan secoisolariciresinol given as the diglycoside (SDG). Eligibility criteria included regular menstrual cycles, no oral contraceptives, a >3-fold increase in 5-year risk, and baseline Ki-67 of >= 2% in areas of hyperplasia in breast tissue sampled by random periareolar fine-needle aspiration (RPFNA) during the follicular phase of the menstrual cycle. SDG (50 mg/d) was given for 12 months, followed by repeat RPFNA. The primary end point was change in Ki-67. Secondary end points included change in cytomorphology, mammographic breast density, serum bioavailable estradiol and testosterone insulin-like growth factor-I and IGF-binding protein-3, and plasma lignan levels. Forty-five of 49 eligible women completed the study with excellent compliance (median = 96%) and few serious side effects (4% grade 3). Median plasma enterolactone increased similar to 9-fold, and total lignans increased 16-fold. Thirty-six (80%) of the 45 evaluable subjects showed a decrease in Ki-67, from a median of 4% (range, 2-16.8%) to 2% (range, 0-15.2%; P < 0.001, Wilcoxon signed rank test). A decrease from baseline in the proportion of women with atypical cytology (P = 0.035) was also observed. Based on favorable risk biomarker modulation and lack of adverse events, we are initiating a randomized trial of SDG versus placebo in premenopausal women. Cancer Prev Res; 3(10); 1342-50. (c) 2010 AACR. C1 [Fabian, Carol J.; Klemp, Jennifer R.; Petroff, Brian K.; Khan, Qamar J.; Sharma, Priyanka; Phillips, Teresa A.; Metheny, Trina; Hughes, Jennifer R.] Univ Kansas, Med Ctr, Dept Internal Med, Kansas City, KS 66160 USA. [Kimler, Bruce F.] Univ Kansas, Med Ctr, Dept Radiat Oncol, Kansas City, KS 66160 USA. [Yeh, Hung-Wen] Univ Kansas, Med Ctr, Dept Biostat, Kansas City, KS 66160 USA. [Zalles, Carola M.] Cedar Pk Reg Med Ctr, Cedar Pk, TX USA. [Setchell, Kenneth D. R.; Zhao, Xueheng] Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA. [Johnson, Karen A.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. RP Fabian, CJ (reprint author), Univ Kansas, Med Ctr, Dept Internal Med, 3901 Rainbow Blvd, Kansas City, KS 66160 USA. EM cfabian@kumc.edu FU National Cancer Institute, NIH [R21 CA117847] FX National Cancer Institute, NIH grant R21 CA117847. NR 83 TC 17 Z9 17 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 J9 CANCER PREV RES JI Cancer Prev. Res. PD OCT PY 2010 VL 3 IS 10 BP 1342 EP 1350 DI 10.1158/1940-6207.CAPR-10-0022 PG 9 WC Oncology SC Oncology GA 658TC UT WOS:000282511300014 PM 20724470 ER PT J AU Patel, KR Brown, VA Jones, DJL Britton, RG Hemingway, D Miller, AS West, KP Booth, TD Perloff, M Crowell, JA Brenner, DE Steward, WP Gescher, AJ Brown, K AF Patel, Ketan R. Brown, Victoria A. Jones, Donald J. L. Britton, Robert G. Hemingway, David Miller, Andrew S. West, Kevin P. Booth, Tristan D. Perloff, Marjorie Crowell, James A. Brenner, Dean E. Steward, William P. Gescher, Andreas J. Brown, Karen TI Clinical Pharmacology of Resveratrol and Its Metabolites in Colorectal Cancer Patients SO CANCER RESEARCH LA English DT Article ID ABERRANT CRYPT FOCI; CHEMOPREVENTIVE AGENT RESVERATROL; TRANS-RESVERATROL; HEALTHY-VOLUNTEERS; WINE; ABSORPTION; HUMANS; CELLS; BIOAVAILABILITY; PROLIFERATION AB Resveratrol is a phytochemical with chemopreventive activity in preclinical rodent models of colorectal carcinogenesis. Antiproliferation is one of the many chemopreventive modes of action it has been shown to engage in. Concentrations of resveratrol, which can be achieved in human tissues after p.o. administration, have not yet been defined. The purpose of this study was to measure concentrations of resveratrol and its metabolites in the colorectal tissue of humans who ingested resveratrol. Twenty patients with histologically confirmed colorectal cancer consumed eight daily doses of resveratrol at 0.5 or 1.0 g before surgical resection. Resveratrol was found to be well tolerated. Normal and malignant biopsy tissue samples were obtained before dosing. Parent compound plus its metabolites resveratrol-3-O-glucuronide, resveratrol-4'-O-glucuronide, resveratrol-3-O-sulfate, resveratrol-4'-O-sulfate, resveratrol sulfate glucuronide, and resveratrol disulfate were identified by high-performance liquid chromatography (HPLC) with UV or mass spectrometric detection in colorectal resection tissue. Quantitation was achieved by HPLC/UV. Cell proliferation, as reflected by Ki-67 staining, was compared in preintervention and postintervention tissue samples. Resveratrol and resveratrol-3- O-glucuronide were recovered from tissues at maximal mean concentrations of 674 and 86.0 nmol/g, respectively. Levels of resveratrol and its metabolites were consistently higher in tissues originating in the right side of the colon compared with the left. Consumption of resveratrol reduced tumor cell proliferation by 5% (P = 0.05). The results suggest that daily p.o. doses of resveratrol at 0.5 or 1.0 g produce levels in the human gastrointestinal tract of an order of magnitude sufficient to elicit anticarcinogenic effects. Resveratrol merits further clinical evaluation as a potential colorectal cancer chemopreventive agent. Cancer Res; 70(19); 7392-9. (C) 2010 AACR. C1 [Patel, Ketan R.] Univ Leicester, Canc Biomarkers & Prevent Grp, Dept Canc Studies & Mol Med, RKCSB,LRI, Leicester LE2 7LX, Leics, England. [Booth, Tristan D.] Pharmascience Inc, Montreal, PQ, Canada. [Perloff, Marjorie; Crowell, James A.] NCI, Chemoprevent Agent Dev Res Grp, Bethesda, MD 20892 USA. [Brenner, Dean E.] Univ Michigan, Sch Med, Dept Internal Med, Ann Arbor, MI USA. [Brenner, Dean E.] Univ Michigan, Sch Med, Dept Pharmacol, Ann Arbor, MI 48109 USA. [Brenner, Dean E.] VA Med Ctr, Ann Arbor, MI USA. RP Patel, KR (reprint author), Univ Leicester, Canc Biomarkers & Prevent Grp, Dept Canc Studies & Mol Med, RKCSB,LRI, Leicester LE2 7LX, Leics, England. EM kp23@le.ac.uk FU US National Cancer Institute [NCI-N01-CN-25025]; Cancer Research UK [C325/A6691]; Experimental Cancer Medicine Centre FX US National Cancer Institute contract NCI-N01-CN-25025, Cancer Research UK program grant C325/A6691, and an Experimental Cancer Medicine Centre grant (Cancer Research UK and UK Department of Health). NR 25 TC 185 Z9 189 U1 4 U2 31 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 OCT 1 PY 2010 VL 70 IS 19 BP 7392 EP 7399 DI 10.1158/0008-5472.CAN-10-2027 PG 8 WC Oncology SC Oncology GA 660MM UT WOS:000282647700004 PM 20841478 ER PT J AU Vineis, P Schatzkin, A Potter, JD AF Vineis, Paolo Schatzkin, Arthur Potter, John D. TI Models of carcinogenesis: an overview SO CARCINOGENESIS LA English DT Review ID PROSTATE-CANCER; LUNG-CANCER; GENE-EXPRESSION; MULTISTAGE CARCINOGENESIS; NUCLEAR-ORGANIZATION; INSULIN-RESISTANCE; COLORECTAL-CANCER; CIGARETTE-SMOKING; MALIGNANT BREAST; TISSUE STRUCTURE AB At least five coherent models of carcinogenesis have been proposed in the history of cancer research in the last century. Model 1 is mainly centered around mutations, and its main focus is on the chemical environment, radiation and viruses. Model 2 has to do mainly with genome instability and it focuses on familiality. Model 3 is based on non-genotoxic mechanisms, and clonal expansion and epigenetics are its main features. We propose a fourth model, which can encompass the previous three, based on the concept of a 'Darwinian' cell selection (we clarify that the term Darwinian needs to be used cautiously, being a short cut for 'somatic cellular selection'). Finally, a fifth model has recently become popular, based on the concept of 'tissue organization'. We describe examples of the five models and how they have been formalized mathematically. The five models largely overlap, both scientifically and historically, but for the sake of clarity, it is useful to treat them separately. We also argue that the five models can be included into a simpler scheme, i.e. two types of models: (i) biological changes in the epithelium alone lead to malignancy and (ii) changes in stroma/extracellular matrix are necessary (along with changes in epithelium) for malignancy. Our description, though simplified, looks realistic, it is able to capture the historical sequence of carcinogenesis theories in the last century and can serve as a frame to make research hypotheses more explicit. C1 [Vineis, Paolo] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, MRC HPA Ctr Environm & Hlth, Dept Epidemiol & Publ Hlth, London W2 1PG, England. [Schatzkin, Arthur] Natl Canc Inst, Div Canc Epidemiol & Genet, Bethesda, MD 20886 USA. [Potter, John D.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. RP Vineis, P (reprint author), Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, MRC HPA Ctr Environm & Hlth, Dept Epidemiol & Publ Hlth, Norfolk Pl, London W2 1PG, England. EM p.vineis@imperial.ac.uk OI Potter, John/0000-0001-5439-1500 NR 83 TC 46 Z9 47 U1 0 U2 15 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD OCT PY 2010 VL 31 IS 10 BP 1703 EP 1709 DI 10.1093/carcin/bgq087 PG 7 WC Oncology SC Oncology GA 661TD UT WOS:000282750100001 PM 20430846 ER PT J AU Olivo-Marston, SE Mechanic, LE Mollerup, S Bowman, ED Remaley, AT Forman, MR Skaug, V Zheng, YL Haugen, A Harris, CC AF Olivo-Marston, Susan E. Mechanic, Leah E. Mollerup, Steen Bowman, Elise D. Remaley, Alan T. Forman, Michele R. Skaug, Vidar Zheng, Yun-Ling Haugen, Aage Harris, Curtis C. TI Serum estrogen and tumor-positive estrogen receptor-alpha are strong prognostic classifiers of non-small-cell lung cancer survival in both men and women SO CARCINOGENESIS LA English DT Article ID HORMONE REPLACEMENT THERAPY; ESR1 GENE AMPLIFICATION; REPRODUCTIVE FACTORS; BREAST-CANCER; CHINESE WOMEN; EXPRESSION; BETA; RISK; ADENOCARCINOMA; SEX AB The role of tumor estrogen receptors (ERs) and serum estrogen in lung cancer is inconclusive. We investigated the hypothesis that ERs and functional single-nucleotide polymorphisms in the estrogen biosynthesis pathway are associated with poorer lung cancer survival. Lung cancer patients (n = 305) from a National Cancer Institute-Maryland (NCI-MD) case-case cohort in the Baltimore metropolitan area were used as a test cohort. To validate, 227 cases from the NCI-MD case-control cohort and 293 cases from a Norwegian lung cancer cohort were studied. Information on demographics, tobacco and reproductive histories was collected in an interviewer-administered questionnaire. Serum estrogen, progesterone, tumor messenger RNA expression of hormone receptors and germ line DNA polymorphisms were analyzed for associations with lung cancer survival. Patients in the highest tertile of serum estrogen had worse survival in all three cohorts (P combined < 0.001). Furthermore, the variant allele of estrogen receptor alpha (ER-alpha) polymorphism (rs2228480) was significantly associated with increased tumor ER-alpha levels and worse survival in all three cohorts [hazard ratio (HR) = 2.59, 95% confidence interval (CI): 1.20- 4.01; HR = 1.76, 95% CI: 1.08-2.87 and HR = 2.85, 95% CI: 1.31-4.36). Other polymorphisms associated with lower serum estrogen correlated with improved survival. Results were independent of gender and hormone replacement therapy. We report a significant association of increased serum estrogen with poorer survival among lung cancer male and female patients. Understanding the genetic control of estrogen biosynthesis and response in lung cancer could lead to improved prognosis and therapy. C1 [Olivo-Marston, Susan E.; Mechanic, Leah E.; Bowman, Elise D.; Harris, Curtis C.] NCI, Human Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Olivo-Marston, Susan E.] Ohio State Univ, Coll Publ Hlth, Div Epidemiol, Columbus, OH 43210 USA. [Mollerup, Steen; Skaug, Vidar; Haugen, Aage] Natl Inst Occupat Hlth, Dept Toxicol, Oslo, Norway. [Remaley, Alan T.] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Forman, Michele R.] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. [Zheng, Yun-Ling] Georgetown Univ, Dept Oncol, Washington, DC 20057 USA. RP Harris, CC (reprint author), NCI, Human Carcinogenesis Lab, Ctr Canc Res, NIH, Bldg 37,Room 3068,37 Convent Dr,MSC 4258, Bethesda, MD 20892 USA. EM curtis_harris@nih.gov FU National Institutes of Health, National Cancer Institute, Center for Cancer Research; Norwegian Cancer Society [0971]; National Cancer Institute FX Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research and the Norwegian Cancer Society (0971); National Cancer Institute Cancer Prevention Fellowship to S. O.-M. NR 53 TC 35 Z9 35 U1 0 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD OCT PY 2010 VL 31 IS 10 BP 1778 EP 1786 DI 10.1093/carcin/bgq156 PG 9 WC Oncology SC Oncology GA 661TD UT WOS:000282750100011 PM 20729390 ER PT J AU Kovalchuk, O Zemp, FJ Filkowski, JN Altamirano, AM Dickey, JS Jenkins-Baker, G Marino, SA Brenner, DJ Bonner, WM Sedelnikova, OA AF Kovalchuk, Olga Zemp, Franz J. Filkowski, Jody N. Altamirano, Alvin M. Dickey, Jennifer S. Jenkins-Baker, Gloria Marino, Stephen A. Brenner, David J. Bonner, William M. Sedelnikova, Olga A. TI microRNAome changes in bystander three-dimensional human tissue models suggest priming of apoptotic pathways SO CARCINOGENESIS LA English DT Article ID INDUCED GENOMIC INSTABILITY; DOUBLE-STRAND BREAKS; IONIZING-RADIATION; C-MYC; EXPRESSION PATTERNS; CANCER CELLS; IN-VITRO; TRAIL; GENE; EXPOSURE AB The radiation-induced bystander effect (RIBE) is a phenomenon whereby unexposed cells exhibit molecular symptoms of stress exposure when adjacent or nearby cells are traversed by ionizing radiation (IR). Recent data suggest that RIBE may be epigenetically mediated by microRNAs (miRNAs), which are small regulatory molecules that target messenger RNA transcripts for translational inhibition. Here, we analyzed microRNAome changes in bystander tissues after alpha-particle microbeam irradiation of three-dimensional artificial human tissues using miRNA microarrays. Our results indicate that IR leads to a deregulation of miRNA expression in bystander tissues. We report that major bystander end points, including apoptosis, cell cycle deregulation and DNA hypomethylation, may be mediated by altered expression of miRNAs. Specifically, c-MYC-mediated upregulation of the miR-17 family was associated with decreased levels of E2F1 and RB1, suggesting a switch to a proliferative state in bystander tissues, while priming these cells for impending death signals. Upregulation of the miR-29 family resulted in decreased levels of its targets DNMT3a and MCL1, consequently affecting DNA methylation and apoptosis. Altered expression of miR-16 led to changes in expression of BCL2, suggesting modulation of apoptosis. Thus, our data clearly show that miRNAs play a profound role in the manifestation of late RIBE end points. In summary, this study creates a roadmap for understanding the role of microRNAome in RIBE and for developing novel RIBE biomarkers. C1 [Kovalchuk, Olga; Zemp, Franz J.; Filkowski, Jody N.; Altamirano, Alvin M.] Univ Lethbridge, Dept Biol Sci, Lethbridge, AB T1K 3M4, Canada. [Dickey, Jennifer S.; Bonner, William M.; Sedelnikova, Olga A.] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Jenkins-Baker, Gloria; Marino, Stephen A.; Brenner, David J.] Columbia Univ, Ctr Radiol Res, Radiat Accelerator Res Facil, New York, NY 10032 USA. RP Kovalchuk, O (reprint author), Univ Lethbridge, Dept Biol Sci, 4401 Univ Dr, Lethbridge, AB T1K 3M4, Canada. EM olga.kovalchuk@uleth.ca FU National Science and Engineering Research Council of Canada; National Institute of Biomedical Imaging and Bioengineering [NIBIB 5 P41 EB002033-12]; National Cancer Institute, Center for Cancer Research, National Institutes of Health (NIH); NIAID; National Cancer Institute, Center for Cancer Research, NIH FX National Science and Engineering Research Council of Canada to O.K., F.J.Z., J.F., A.A.; The National Institute of Biomedical Imaging and Bioengineering to G.J.-B., S.A.M., D.J.B. (NIBIB 5 P41 EB002033-12); Intramural Research Program of the National Cancer Institute, Center for Cancer Research, National Institutes of Health (NIH) and the NIAID Radiation/Nuclear Countermeasures Program; the Intramural Research Program of the National Cancer Institute, Center for Cancer Research, NIH to J.S.D., W.M.B., O.A.S. NR 58 TC 28 Z9 33 U1 0 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD OCT PY 2010 VL 31 IS 10 BP 1882 EP 1888 DI 10.1093/carcin/bgq119 PG 7 WC Oncology SC Oncology GA 661TD UT WOS:000282750100023 PM 20643754 ER PT J AU Hodgson, R AF Hodgson, Robert, Jr. TI Translating the New Testament: Text, Translation, Theology SO CATHOLIC BIBLICAL QUARTERLY LA English DT Book Review C1 [Hodgson, Robert, Jr.] Amer Bible Soc, Nida Inst Bibl Scholarship, New York, NY 10023 USA. RP Hodgson, R (reprint author), Amer Bible Soc, Nida Inst Bibl Scholarship, New York, NY 10023 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU CATHOLIC BIBLICAL ASSOC AMER PI WASHINGTON PA CATHOLIC UNIV AMERICA, 620 MICHIGAN AVE, NE, WASHINGTON, DC 20064 USA SN 0008-7912 EI 2163-2529 J9 CATH BIBLICAL QUART JI Cathol. Biblic. Q. PD OCT PY 2010 VL 72 IS 4 BP 877 EP 879 PG 3 WC Religion SC Religion GA V38OP UT WOS:000209353000068 ER PT J AU Pavri, R Gazumyan, A Jankovic, M Di Virgilio, M Klein, I Ansarah-Sobrinho, C Resch, W Yamane, A San-Martin, BR Barreto, V Nieland, TJ Root, DE Casellas, R Nussenzweig, MC AF Pavri, Rushad Gazumyan, Anna Jankovic, Mila Di Virgilio, Michela Klein, Isaac Ansarah-Sobrinho, Camilo Resch, Wolfgang Yamane, Arito San-Martin, Bernardo Reina Barreto, Vasco Nieland, Thomas J. Root, David E. Casellas, Rafael Nussenzweig, Michel C. TI Activation-Induced Cytidine Deaminase Targets DNA at Sites of RNA Polymerase II Stalling by Interaction with Spt5 SO CELL LA English DT Article ID CLASS-SWITCH RECOMBINATION; SINGLE-STRANDED-DNA; TRANSCRIPTION ELONGATION-FACTOR; ANTIBODY DIVERSIFICATION ENZYME; PROTEIN-KINASE-A; CENTER B-CELLS; SOMATIC HYPERMUTATION; C-MYC; IMMUNOGLOBULIN GENES; P-TEFB AB Activation-induced cytidine deaminase (AID) initiates antibody gene diversification by creating U:G mismatches. However, AID is not specific for antibody genes; Off-target lesions can activate oncogenes or cause chromosome translocations. Despite its importance in these transactions little is known about how AID finds its targets. We performed an shRNA screen to identify factors required for class switch recombination (CSR) of antibody loci. We found that Spt5, a factor associated with stalled RNA polymerase II (Pol II) and single stranded DNA (ssDNA), is required for CSR. Spt5 interacts with AID, it facilitates association between AID and Pol II, and AID recruitment to its Ig and non-Ig targets. ChIP-seq experiments reveal that Spt5 colocalizes with AID and stalled Pol II. Further, Spt5 accumulation at sites of Pol II stalling is predictive of AID-induced mutation. We propose that AID is targeted to sites of Pol II stalling in part via its association with Spt5. C1 [Pavri, Rushad; Gazumyan, Anna; Jankovic, Mila; Di Virgilio, Michela; Klein, Isaac; San-Martin, Bernardo Reina; Barreto, Vasco; Nussenzweig, Michel C.] Rockefeller Univ, Lab Mol Immunol, New York, NY 10065 USA. [Gazumyan, Anna; Nussenzweig, Michel C.] Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10065 USA. [Ansarah-Sobrinho, Camilo; Resch, Wolfgang; Yamane, Arito; Casellas, Rafael] NCI, Natl Inst Arthrit & Musculoskeletal & Skin Dis NI, Ctr Canc Res, Bethesda, MD 20892 USA. [San-Martin, Bernardo Reina] Univ Strasbourg, INSERM U964, CNRS UMR7104, IGBMC, F-67404 Illkirch Graffenstaden, France. [Barreto, Vasco] Inst Gulbenkian Ciencias, Lab Epigenet Soma, P-2780156 Oeiras, Portugal. [Nieland, Thomas J.] MIT, Broad Inst, RNAi Platform, Cambridge, MA 02142 USA. RP Nussenzweig, MC (reprint author), Rockefeller Univ, Lab Mol Immunol, New York, NY 10065 USA. EM casellar@mail.nih.gov; nussen@mail.rockefeller.edu RI Yamane, Arito/A-2959-2013; Barreto, Vasco/D-4275-2012; Reina-San-Martin, Bernardo/I-9484-2016 OI Barreto, Vasco/0000-0002-0010-8607; Reina-San-Martin, Bernardo/0000-0003-2083-6166 FU Cancer Research Institute; NIH [AI037526] FX We thank members of the Nussenzweig lab for helpful discussions, Klara Velinzon for FACS sorting, and Tom Eisenreich and David Bosque for animal management. We thank Drs Jayanta Chaudhuri and Urszula Nowak for ChIP protocols and anti-AID antibody, Dr. Sohail Malik for generously providing purified recombinant DSIF and Dr. Alan Derr for assistance with informatics. M.D.V. is a fellow of the American-Italian Cancer Foundation. R.P was a recipient of The Irvington Institute Postdoctoral Fellowship of the Cancer Research Institute. The work was supported by NIH grant (AI037526) to M.C.N.M.C.N. is a Howard Hughes Medical Institute Investigator. NR 87 TC 177 Z9 181 U1 1 U2 17 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD OCT 1 PY 2010 VL 143 IS 1 BP 122 EP 133 DI 10.1016/j.cell.2010.09.017 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 656UC UT WOS:000282362000019 PM 20887897 ER PT J AU Zhang, JH Panicker, LM Seigneur, EM Lin, L House, CD Morgan, W Chen, WC Mehta, H Haj-Ali, M Yu, ZX Simonds, WF AF Zhang, J-H Panicker, L. M. Seigneur, E. M. Lin, L. House, C. D. Morgan, W. Chen, W. C. Mehta, H. Haj-Ali, M. Yu, Z-X Simonds, W. F. TI Cytoplasmic polyadenylation element binding protein is a conserved target of tumor suppressor HRPT2/CDC73 SO CELL DEATH AND DIFFERENTIATION LA English DT Article DE Akt1S1; longevity; Paf1 complex; parafibromin; PRAS40 ID FAMILIAL ISOLATED HYPERPARATHYROIDISM; RNA-POLYMERASE-II; CELLULAR SENESCENCE; PAF1 COMPLEX; HRPT2 GENE; PARAFIBROMIN; CPEB; DROSOPHILA; TRANSCRIPTION; TRANSLATION AB Parafibromin, a tumor suppressor protein encoded by HRPT2/CDC73 and implicated in parathyroid cancer and the hyperparathyroidism-jaw tumor (HPT-JT) familial cancer syndrome, is part of the PAF1 transcriptional regulatory complex. Parafibromin has been implicated in apoptosis and growth arrest, but the mechanism by which its loss of function promotes neoplasia is poorly understood. In this study we report that a hypomorphic allele of hyrax (hyx), the Drosophila homolog of HRPT2/CDC73, rescues the loss-of-ventral-eye phenotype of lobe (Akt1s1). Such rescue is consistent with previous reports that hyx/parafibromin is required for the nuclear transduction of Wingless (Wg)/Wnt signals and that Wg signaling antagonizes lobe function. A screen using double hyx/lobe heterozygotes identified an additional interaction with orb and orb2, the homologs of mammalian cytoplasmic polyadenylation element binding protein (CPEB), a translational regulatory protein. Hyx and orb2 heterozygotes lived longer and were more resistant to starvation than controls. In mammalian cells, knockdown of parafibromin expression reduced levels of CPEB1. Chromatin immunoprecipitation (ChIP) showed occupancy of CPEB1 by endogenous parafibromin. Bioinformatic analysis revealed a significant overlap between human transcripts potentially regulated by parafibromin and CPEB. These results show that parafibromin may exert both transcriptional and, through CPEB, translational control over a subset of target genes and that loss of parafibromin (and CPEB) function may promote tumorigenesis in part by conferring resistance to nutritional stress. Cell Death and Differentiation (2010) 17, 1551-1565; doi:10.1038/cdd.2010.32; published online 26 March 2010 C1 [Simonds, W. F.] NIDDKD, Metab Dis Branch, NIH, Bethesda, MD 20892 USA. [Chen, W. C.] NIDDKD, Genom Core Lab, Bethesda, MD 20892 USA. [Yu, Z-X] NHLBI, Genet & Dev Biol Ctr, NIH, Bethesda, MD 20892 USA. RP Simonds, WF (reprint author), NIDDKD, Metab Dis Branch, NIH, Bldg 10 Room 8C-101,10 Ctr Dr MSC 1752, Bethesda, MD 20892 USA. EM wfs@helix.nih.gov FU National Institute of Diabetes and Digestive and Kidney Diseases FX We are grateful to Sunita Agarwal and Stephen Marx for encouragement and helpful discussions. This research was supported by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases. NR 34 TC 12 Z9 13 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1350-9047 EI 1476-5403 J9 CELL DEATH DIFFER JI Cell Death Differ. PD OCT PY 2010 VL 17 IS 10 BP 1551 EP 1565 DI 10.1038/cdd.2010.32 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 649CQ UT WOS:000281745200004 PM 20339377 ER PT J AU Linkous, A Yazlovitskaya, E AF Linkous, Amanda Yazlovitskaya, Eugenia TI Cytosolic phospholipase A2 as a mediator of disease pathogenesis SO CELLULAR MICROBIOLOGY LA English DT Review ID CELL LUNG-CANCER; IRRADIATED VASCULAR ENDOTHELIUM; COLLAGEN-INDUCED ARTHRITIS; PSEUDOMONAS-AERUGINOSA; IONIZING-RADIATION; TRANSEPITHELIAL MIGRATION; TUMOR ANGIOGENESIS; SHIGELLA-FLEXNERI; ARACHIDONIC-ACID; MICE DEFICIENT AB P>As efficient catalysts, enzymes help maintain a variety of biological and chemical transformations necessary for cellular metabolism and normal physiology. Unfortunately, pathogenic microbes can also exploit enzymatic reactions in an attempt to spread infection. Cytosolic phospholipase A2 (cPLA(2)) is an enzyme that is responsible for the hydrolysis of membrane phospholipids such as phosphatidylcholine. Following activation, cPLA(2) cleaves phosphatidylcholine to yield free fatty acid and lysophosphatidylcholine. Both of these products and their downstream metabolites initiate a network of signalling cascades that influence cellular viability and inflammation. Recent observations have shown that viral and bacterial agents often target this intricate organization of signalling molecules. This review briefly discusses the role of cPLA(2) in the biological response to disease-causing pathogens and injury, the immunological process and tumour progression. C1 [Yazlovitskaya, Eugenia] Vanderbilt Univ, Dept Med, Div Nephrol, Nashville, TN 37232 USA. [Yazlovitskaya, Eugenia] Vanderbilt Univ, Vanderbilt Ingram Canc Ctr, Nashville, TN 37232 USA. [Linkous, Amanda] NCI, Neurooncol Branch, NIH, Bethesda, MD 20892 USA. RP Yazlovitskaya, E (reprint author), Vanderbilt Univ, Dept Med, Div Nephrol, Nashville, TN 37232 USA. EM eugenia.yazlovitskaya@vanderbilt.edu NR 62 TC 34 Z9 35 U1 0 U2 11 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1462-5814 J9 CELL MICROBIOL JI Cell Microbiol. PD OCT PY 2010 VL 12 IS 10 BP 1369 EP 1377 DI 10.1111/j.1462-5822.2010.01505.x PG 9 WC Cell Biology; Microbiology SC Cell Biology; Microbiology GA 647RL UT WOS:000281636200001 PM 20642808 ER PT J AU Belov, GA Kovtunovych, G Jackson, CL Ehrenfeld, E AF Belov, George A. Kovtunovych, Gennadiy Jackson, Catherine L. Ehrenfeld, Ellie TI Poliovirus replication requires the N-terminus but not the catalytic Sec7 domain of ArfGEF GBF1 SO CELLULAR MICROBIOLOGY LA English DT Article ID NUCLEOTIDE-EXCHANGE FACTOR; ADP-RIBOSYLATION FACTORS; TATA-BINDING PROTEIN; POLYMERASE-II TRANSCRIPTION; BREFELDIN-A; RNA-POLYMERASE; MEMBRANE ASSOCIATION; 3C PROTEASE; COPI COAT; CIS-GOLGI AB P>Viruses are intracellular parasites whose reproduction relies on factors provided by the host. The cellular protein GBF1 is critical for poliovirus replication. Here we show that the contribution of GBF1 to virus replication is different from its known activities in uninfected cells. Normally GBF1 activates the ADP-ribosylation factor (Arf) GTPases necessary for formation of COPI transport vesicles. GBF1 function is modulated by p115 and Rab1b. However, in polio-infected cells, p115 is degraded and neither p115 nor Rab1b knock-down affects virus replication. Poliovirus infection is very sensitive to brefeldin A (BFA), an inhibitor of Arf activation by GBF1. BFA targets the catalytic Sec7 domain of GBF1. Nevertheless the BFA block of polio replication is rescued by expression of only the N-terminal region of GBF1 lacking the Sec7 domain. Replication of BFA-resistant poliovirus in the presence of BFA is uncoupled from Arf activation but is dependent on GBF1. Thus the function(s) of this protein essential for viral replication can be separated from those required for cellular metabolism. C1 [Belov, George A.; Ehrenfeld, Ellie] NIAID, Bethesda, MD 20892 USA. [Kovtunovych, Gennadiy] NICHHD, Bethesda, MD 20892 USA. [Jackson, Catherine L.] CNRS, Lab Enzymol & Biochim Struct, F-91198 Gif Sur Yvette, France. RP Ehrenfeld, E (reprint author), NIAID, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM eehrenfeld@niaid.nih.gov RI Jackson, Catherine/A-3421-2013; Belov, George/B-4625-2008 OI Jackson, Catherine/0000-0002-0843-145X; Belov, George/0000-0002-0892-1731 FU NIAID, National Institutes of Health FX This work was supported in part by the intramural programme of the NIAID, National Institutes of Health. We thank members of Elizabeth Stzul's laboratory for reagents and helpful discussion of p115 experiments. We thank Marie-Pierre Golinelli-Cohen for construction of plasmids and for critical reading of the manuscript. NR 60 TC 33 Z9 34 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1462-5814 J9 CELL MICROBIOL JI Cell Microbiol. PD OCT PY 2010 VL 12 IS 10 BP 1463 EP 1479 DI 10.1111/j.1462-5822.2010.01482.x PG 17 WC Cell Biology; Microbiology SC Cell Biology; Microbiology GA 647RL UT WOS:000281636200008 PM 20497182 ER PT J AU Mustafa, T Walsh, J Grimaldi, M Eiden, LE AF Mustafa, Tomris Walsh, James Grimaldi, Maurizio Eiden, Lee E. TI PAC1hop receptor activation facilitates catecholamine secretion selectively through 2-APB-sensitive Ca2+ channels in PC12 cells SO CELLULAR SIGNALLING LA English DT Article DE PACAP; Calcium; Secretion; Chromaffin; PC12; 2-APB ID ADRENAL CHROMAFFIN CELLS; ADENYLATE-CYCLASE; CALCIUM-CHANNELS; SIGNAL-TRANSDUCTION; POLYPEPTIDE PACAP; SPLICE VARIANTS; CYCLIC-AMP; INFLUX; ELEVATION; RELEASE AB PACAP is a critical regulator of long-term catecholamine secretion from the adrenal medulla in vivo, however the receptor or pathways for Ca2+ entry triggering acute and sustained secretion have not been adequately characterized. We have previously cloned the bovine adrenal chromaffin cell PAC1 receptor that contains the molecular determinants required for PACAP-induced Ca2+ elevation and is responsible for imparting extracellular Ca2+ influx-dependent secretory competence in PC12 cells. Here, we use this cell model to gain mechanistic insights into PAC1hop-dependent Ca2+ pathways responsible for catecholamine secretion. PACAP-modulated extracellular Ca2+ entry in PC12 cells could be partially blocked with nimodipine, an inhibitor of L-type VGCCs and partially blocked by 2-APB, an inhibitor and modulator of various transient receptor potential (TRP) channels. Despite the co-existence of these two modes of Ca2+ entry, sustained catecholamine secretion in PC12 cells was exclusively modulated by 2-APB-sensitive Ca2+ channels. While IP3 generation occurred after PACAP exposure, most PACAP-induced Ca2+ mobilization involved release from ryanodine-gated cytosolic stores. 2-APB-sensitive Ca2+ influx, and subsequent catecholamine secretion was however not functionally related to intracellular Ca2+ mobilization and store depletion. The reconstituted PAC1hop-expessing PC12 cell model therefore recapitulates both PACAP-induced Ca2+ release from ER stores and extracellular Ca2+ entry that restores PACAP-induced secretory competence in neuroendocrine cells. We demonstrate here that although bPAC1hop receptor occupancy induces Ca2+ entry through two independent sources. VGCCs and 2-APB-sensitive channels, only the latter contributes importantly to sustained vesicular catecholamine release that is a fundamental characteristic of this neuropeptide system. These results emphasize the importance of establishing functional linkages between Ca2+ signaling pathways initiated by pleotrophic signaling molecules such as PACAP, and physiologically important downstream events, such as secretion, triggered by them. Published by Elsevier Inc. C1 [Mustafa, Tomris; Walsh, James; Eiden, Lee E.] Natl Inst Mental Hlth, Mol Neurosci Sect, Lab Cellular & Mol Regulat, Bethesda, MD 20892 USA. [Grimaldi, Maurizio] So Res Inst, Neuropharmacol Lab, Dept Biochem, Drug Discovery Div, Birmingham, AL 35205 USA. RP Eiden, LE (reprint author), Natl Inst Mental Hlth, Mol Neurosci Sect, Lab Cellular & Mol Regulat, Bldg 49,Room 5A-68,9000 Rockville Pike, Bethesda, MD 20892 USA. EM eidenl@mail.nih.gov OI Grimaldi, Maurizio/0000-0002-7331-7055; Eiden, Lee/0000-0001-7524-944X FU National Institute of Mental Health [ZO1-MH002386-23] FX This is work is supported by National Institute of Mental Health-Intramural Research Program Project ZO1-MH002386-23. Dr Tomris Mustafa and Jamie Walsh additionally supported by the Julius Axelrod Fellowship from the National Institute of Mental Health-Intramural Research Program. We would like to thank Chang-Mei Hsu and David Huddleston for technical assistance (Section on Molecular Neuroscience, NIMH). We also thank Dr Tamas Balla and Dr James T. Russell (NICHD, NIH-Intramural Research Program) for advice and consultation in preparation of this report. NR 29 TC 12 Z9 12 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0898-6568 J9 CELL SIGNAL JI Cell. Signal. PD OCT PY 2010 VL 22 IS 10 BP 1420 EP 1426 DI 10.1016/j.cellsig.2010.05.005 PG 7 WC Cell Biology SC Cell Biology GA 634ZK UT WOS:000280625000004 PM 20471475 ER PT J AU Harel, A Gilaie-Dotan, S Malach, R Bentin, S AF Harel, Assaf Gilaie-Dotan, Sharon Malach, Rafael Bentin, Shlomo TI Top-Down Engagement Modulates the Neural Expressions of Visual Expertise SO CEREBRAL CORTEX LA English DT Article DE fMRI; object recognition; top-down effects; visual cortex; visual expertise ID FUSIFORM FACE AREA; LATERAL OCCIPITAL COMPLEX; HUMAN EXTRASTRIATE CORTEX; VENTRAL TEMPORAL CORTEX; OBJECT RECOGNITION; SELECTIVE ATTENTION; CORTICAL NETWORK; PERCEPTION; FMRI; ACTIVATION AB Perceptual expertise is traditionally associated with enhanced brain activity in response to objects of expertise in category-selective visual cortex, primarily face-selective regions. We reevaluated this view by investigating whether the brain activity associated with expertise in object recognition is limited to category-selective cortex and specifically whether the extent of expertise-related activity manifests automatically or whether it can be top-down modulated. We conducted 2 functional magnetic resonance imaging studies comparing changes in hemodynamic activity associated with car expertise in a conventional 1-back task (Experiment 1) and when the task relevance of cars was explicitly manipulated (Experiment 2). Whole-brain analysis unveiled extensive expertise-related activity throughout the visual cortex, starting as early as V1 and extending into nonvisual areas. However, when the cars were task irrelevant, the expertise-related activity drastically diminished, indeed, becoming similar to the activity elicited by cars in novices. We suggest that expertise entails voluntary top-down engagement of multiple neural networks in addition to stimulus-driven activation associated with perceptual mechanisms. C1 [Harel, Assaf; Bentin, Shlomo] Hebrew Univ Jerusalem, Dept Psychol, IL-91905 Jerusalem, Israel. [Gilaie-Dotan, Sharon; Malach, Rafael] Weizmann Inst Sci, Dept Neurobiol, IL-76100 Rehovot, Israel. [Bentin, Shlomo] Hebrew Univ Jerusalem, Ctr Neural Computat, IL-91904 Jerusalem, Israel. RP Harel, A (reprint author), NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. EM assaf.harel@nih.gov OI Harel, Assaf/0000-0002-4899-6156 FU National Institute of Mental Health [R01 MH 64458]; Israel Foundations Trustees Program for the Advancement of Research in the Social Sciences FX National Institute of Mental Health (R01 MH 64458 to S.B.); Israel Foundations Trustees Program for the Advancement of Research in the Social Sciences (Research Grant for Doctoral Students in the Social Sciences to A.H.). NR 54 TC 37 Z9 37 U1 2 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD OCT PY 2010 VL 20 IS 10 BP 2304 EP 2318 DI 10.1093/cercor/bhp316 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 648SX UT WOS:000281715500005 PM 20133358 ER PT J AU Seitz, AE Olivier, KN Steiner, CA de Oca, RM Holland, SM Prevots, DR AF Seitz, Amy E. Olivier, Kenneth N. Steiner, Claudia A. de Oca, Ruben Montes Holland, Steven M. Prevots, D. Rebecca TI Trends and Burden of Bronchiectasis-Associated Hospitalizations in the United States, 1993-2006 SO CHEST LA English DT Article ID ORPHAN DISEASE; COST AB Background: Current data on bronchiectasis prevalence, trends, and risk factors are lacking; such data are needed to estimate the burden of disease and for improved medical care and public health resource allocation. The objective of the present study was to estimate the trends and burden of bronchiectasis-associated hospitalizations in the United States. Methods: We extracted hospital discharge records containing International Classification of Diseases, 9th Revision, Clinical Modification codes for bronchiectasis (494, 494.0, and 494.1) as any discharge diagnosis from the State Inpatient Databases from the Agency for Healthcare Research and Quality. Discharge records were extracted for 12 states with complete and continuous reporting from 1993 to 2006. Results: The average annual age-adjusted hospitalization rate from 1993 to 2006 was 16.5 hospitalizations per 100,000 population. From 1993 to 2006, the age-adjusted rate increased significantly, with an average annual percentage increase of 2.4% among men and 3.0% among women. Women and persons aged >60 years had the highest rate of bronchiectasis-associated hospitalizations. The median cost for inpatient care was 7,827 US dollars (USD) (range, 13-543,914 USD). Conclusions: The average annual age-adjusted rate of bronchiectasis-associated hospitalizations increased from 1993 to 2006. This study furthers the understanding of the impact of bronchiectasis and demonstrates the need for further research to identify risk factors and reasons for the increasing burden. CHEST 2010; 138(4):944-949 C1 [Seitz, Amy E.; Olivier, Kenneth N.; de Oca, Ruben Montes; Holland, Steven M.; Prevots, D. Rebecca] NIAID, NIH, Bethesda, MD 20892 USA. [Steiner, Claudia A.] Agcy Healthcare Res & Qual, Rockville, MD USA. RP Prevots, DR (reprint author), NIAID, NIH, 8 W Dr,MSC 2665, Bethesda, MD 20892 USA. EM rprevots@niaid.nih.gov FU National Institutes of Health, National Institute of Allergy and Infectious Diseases FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases. NR 21 TC 64 Z9 71 U1 1 U2 3 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD OCT PY 2010 VL 138 IS 4 BP 944 EP 949 DI 10.1378/chest.10-0099 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 664YQ UT WOS:000283000500031 PM 20435655 ER PT J AU Musunuru, K Post, WS Herzog, W Shen, HQ O'Connell, JR McArdle, PF Ryan, KA Gibson, Q Cheng, YC Clearfield, E Johnson, AD Tofler, G Yang, QO O'Donnell, CJ Becker, DM Yanek, LR Becker, LC Faraday, N Bielak, LF Peyser, PA Shuldiner, AR Mitchell, BD AF Musunuru, Kiran Post, Wendy S. Herzog, William Shen, Haiqing O'Connell, Jeffrey R. McArdle, Patrick F. Ryan, Kathleen A. Gibson, Quince Cheng, Yu-Ching Clearfield, Elizabeth Johnson, Andrew D. Tofler, Geoffrey Yang, Qiong O'Donnell, Christopher J. Becker, Diane M. Yanek, Lisa R. Becker, Lewis C. Faraday, Nauder Bielak, Lawrence F. Peyser, Patricia A. Shuldiner, Alan R. Mitchell, Braxton D. TI Association of Single Nucleotide Polymorphisms on Chromosome 9p21.3 With Platelet Reactivity A Potential Mechanism for Increased Vascular Disease SO CIRCULATION-CARDIOVASCULAR GENETICS LA English DT Article DE genetics; cardiovascular diseases; coronary disease; stroke; blood platelets ID CORONARY-ARTERY-DISEASE; GENOME-WIDE ASSOCIATION; MYOCARDIAL-INFARCTION; HEART-DISEASE; 4 SNPS; ISCHEMIC-STROKE; CONFER RISK; LOCUS; ATHEROSCLEROSIS; SUSCEPTIBILITY AB Background-Genome-wide association studies have identified a locus on chromosome 9p21.3 to be strongly associated with myocardial infarction/coronary artery disease and ischemic stroke. To gain insights into the mechanisms underlying these associations, we hypothesized that single nucleotide polymorphisms (SNPs) in this region would be associated with platelet reactivity across multiple populations. Methods and Results-Subjects in the initial population included 1402 asymptomatic Amish adults in whom we measured platelet reactivity (n=788) and coronary artery calcification (CAC) (n=939). Platelet reactivity on agonist stimulation was measured by impedance aggregometry, and CAC was measured by electron beam CT. Twenty-nine SNPs at the 9p21.3 locus were genotyped using the Affymetrix 500K array. Twelve correlated SNPs in the locus were significantly associated with platelet reactivity (all P <= 0.001). The SNP most strongly associated with platelet reactivity, rs10965219 (P=0.0002), also was associated with CAC (P=0.002) along with 9 other SNPs (all P<0.004). Association of rs10965219 with platelet reactivity persisted after adjustment for CAC, a measure of underlying atherosclerotic burden known to affect platelet reactivity. We then tested rs10965219 for association with platelet function in 2364 subjects from the Framingham Heart Study and 1169 subjects from the Genetic Study of Aspirin Responsiveness. The rs10965219 G allele (frequency approximate to 51% across all 3 populations) was significantly associated with higher platelet reactivity in the Framingham Heart Study (P=0.001) and trended toward higher reactivity in the Genetic Study of Aspirin Responsiveness (P=0.087); the combined P value for metaanalysis was 0.0002. Conclusions-These results suggest that risk alleles at 9p21.3 locus may have pleiotropic effects on myocardial infarction/coronary artery disease and stroke risk, possibly through their influence on platelet reactivity. (Circ Cardiovasc Genet. 2010;3:445-453.) C1 [Shen, Haiqing; O'Connell, Jeffrey R.; McArdle, Patrick F.; Ryan, Kathleen A.; Gibson, Quince; Cheng, Yu-Ching; Clearfield, Elizabeth; Shuldiner, Alan R.; Mitchell, Braxton D.] Univ Maryland, Div Endocrinol Diabet & Nutr, Sch Med, Baltimore, MD 21201 USA. [Musunuru, Kiran; Post, Wendy S.; Herzog, William; Becker, Lewis C.] Johns Hopkins Univ, Sch Med, Dept Med, Div Cardiol, Baltimore, MD 21205 USA. [Becker, Diane M.; Yanek, Lisa R.] Johns Hopkins Univ, Dept Med, Div Gen Internal Med, Baltimore, MD USA. [Faraday, Nauder] Johns Hopkins Univ, Dept Med, Dept Anesthesiol Crit Care Med, Baltimore, MD USA. [Bielak, Lawrence F.; Peyser, Patricia A.] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA. [Shuldiner, Alan R.] Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Baltimore, MD 21218 USA. [Johnson, Andrew D.; Yang, Qiong; O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Johnson, Andrew D.; O'Donnell, Christopher J.] NHLBI, Div Intramural Res, Bethesda, MD 20892 USA. [Tofler, Geoffrey] Univ Sydney, Royal N Shore Hosp, Sydney, NSW 2006, Australia. [Yang, Qiong] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. RP Mitchell, BD (reprint author), Univ Maryland, Div Endocrinol Diabet & Nutr, Sch Med, 660 W Redwood St,Room 492, Baltimore, MD 21201 USA. EM bmitchel@medicine.umaryland.edu RI Johnson, Andrew/G-6520-2013; Yang, Qiong/G-5438-2014; OI Mitchell, Braxton/0000-0003-4920-4744 FU National Institutes of Health (NIH) [U01 HL72515, R01 HL088119]; University of Maryland General Clinical Research Center [M01 RR 16500]; American Federation of Aging Research; Mid-Atlantic Nutrition and Obesity Research Center [P30 DK072488]; Baltimore Veterans Administration Medical Center Geriatric Research and Education Clinical Center; National Heart, Lung, and Blood Institute (NHLBI) through the PROGENI [U01 HL72518]; STAMPEED [R01 HL087698-01]; NHLBI FHS [N01-HC-25195]; Affymetrix, Inc [N02-HL-6-4278, R01 HL48157]; Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center FX This work was supported by National Institutes of Health (NIH) research grants U01 HL72515 and R01 HL088119, a University of Maryland General Clinical Research Center grant (M01 RR 16500), and the Paul Beeson Physician Faculty Scholars in Aging Program of the American Federation of Aging Research. Partial funding also was provided by the Mid-Atlantic Nutrition and Obesity Research Center (P30 DK072488) and the Baltimore Veterans Administration Medical Center Geriatric Research and Education Clinical Center. GeneSTAR was supported by the National Heart, Lung, and Blood Institute (NHLBI) through the PROGENI (U01 HL72518) and STAMPEED (R01 HL087698-01) consortia. This research was conducted in part using data and resources from the NIH NHLBI FHS and Boston University School of Medicine and was supported by the NHLBI FHS (Contract No. N01-HC-25195) and its contract with Affymetrix, Inc, for genotyping services (Contract No. N02-HL-6-4278) and through R01 HL48157. The analyses reflect resource development and intellectual input from the FHS investigators participating in the SNP Health Association Resource (SHARe) project. A portion of this research used the Linux Cluster for Genetic Analysis (LinGA-II) funded by the Robert Dawson Evans Endowment of the Department of Medicine at Boston University School of Medicine and Boston Medical Center. NR 43 TC 33 Z9 37 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1942-325X J9 CIRC-CARDIOVASC GENE JI Circ.-Cardiovasc. Genet. PD OCT PY 2010 VL 3 IS 5 BP 445 EP 453 DI 10.1161/CIRCGENETICS.109.923508 PG 9 WC Cardiac & Cardiovascular Systems; Genetics & Heredity SC Cardiovascular System & Cardiology; Genetics & Heredity GA 666ZX UT WOS:000283163100008 PM 20858905 ER PT J AU Preuss, M Konig, IR Thompson, JR Erdmann, J Absher, D Assimes, TL Blankenberg, S Boerwinkle, E Chen, L Cupples, LA Hall, AS Halperin, E Hengstenberg, C Holm, H Laaksonen, R Li, MY Marz, W McPherson, R Musunuru, K Nelson, CP Burnett, MS Epstein, SE O'Donnell, CJ Quertermous, T Rader, DJ Roberts, R Schillert, A Stefansson, K Stewart, AFR Thorleifsson, G Voight, BF Wells, GA Ziegler, A Kathiresan, S Reilly, MP Samani, NJ Schunkert, H AF Preuss, Michael Koenig, Inke R. Thompson, John R. Erdmann, Jeanette Absher, Devin Assimes, Themistocles L. Blankenberg, Stefan Boerwinkle, Eric Chen, Li Cupples, L. Adrienne Hall, Alistair S. Halperin, Eran Hengstenberg, Christian Holm, Hilma Laaksonen, Reijo Li, Mingyao Maerz, Winfried McPherson, Ruth Musunuru, Kiran Nelson, Christopher P. Burnett, Mary Susan Epstein, Stephen E. O'Donnell, Christopher J. Quertermous, Thomas Rader, Daniel J. Roberts, Robert Schillert, Arne Stefansson, Kari Stewart, Alexandre F. R. Thorleifsson, Gudmar Voight, Benjamin F. Wells, George A. Ziegler, Andreas Kathiresan, Sekar Reilly, Muredach P. Samani, Nilesh J. Schunkert, Heribert CA CARDIoGRAM Consortium TI Design of the Coronary ARtery DIsease Genome-Wide Replication And Meta-Analysis (CARDIoGRAM) Study A Genome-Wide Association Meta-analysis Involving More Than 22 000 Cases and 60 000 Controls SO CIRCULATION-CARDIOVASCULAR GENETICS LA English DT Article DE coronary artery disease; myocardial infarction; meta-analysis; genetics ID MYOCARDIAL-INFARCTION; SUSCEPTIBILITY LOCUS; VARIANT; ATHEROSCLEROSIS; HEART; 9P21; RISK AB Background-Recent genome-wide association studies (GWAS) of myocardial infarction (MI) and other forms of coronary artery disease (CAD) have led to the discovery of at least 13 genetic loci. In addition to the effect size, power to detect associations is largely driven by sample size. Therefore, to maximize the chance of finding novel susceptibility loci for CAD and MI, the Coronary ARtery DIsease Genome-wide Replication And Meta-analysis (CARDIoGRAM) consortium was formed. Methods and Results-CARDIoGRAM combines data from all published and several unpublished GWAS in individuals with European ancestry; includes >22 000 cases with CAD, MI, or both and >60 000 controls; and unifies samples from the Atherosclerotic Disease VAscular functioN and genetiC Epidemiology study, CADomics, Cohorts for Heart and Aging Research in Genomic Epidemiology, deCODE, the German Myocardial Infarction Family Studies I, II, and III, Ludwigshafen Risk and Cardiovascular Heath Study/AtheroRemo, MedStar, Myocardial Infarction Genetics Consortium, Ottawa Heart Genomics Study, PennCath, and the Wellcome Trust Case Control Consortium. Genotyping was carried out on Affymetrix or Illumina platforms followed by imputation of genotypes in most studies. On average, 2.2 million single nucleotide polymorphisms were generated per study. The results from each study are combined using meta-analysis. As proof of principle, we meta-analyzed risk variants at 9p21 and found that rs1333049 confers a 29% increase in risk for MI per copy (P=2x10(-20)). Conclusion-CARDIoGRAM is poised to contribute to our understanding of the role of common genetic variation on risk for CAD and MI. (Circ Cardiovasc Genet. 2010;3:475-483.) C1 [Assimes, Themistocles L.; Quertermous, Thomas] Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA. [Blankenberg, Stefan] Johannes Gutenberg Univ Mainz, Med Klin & Poliklin, Mainz, Germany. [Boerwinkle, Eric] Univ Texas Houston, Hlth Sci Ctr, Ctr Human Genet, Houston, TX USA. [Boerwinkle, Eric] Inst Mol Med, Houston, TX USA. [Chen, Li; McPherson, Ruth; Roberts, Robert; Stewart, Alexandre F. R.] Univ Ottawa, John & Jennifer Ruddy Canadian Cardiovasc Gen Ctr, Ottawa, ON, Canada. Boston Univ, Dept Biostat & Epidemiol, Boston, MA 02215 USA. [O'Donnell, Christopher J.] NHLBI, Framingham, MA USA. [Hall, Alistair S.] Univ Leeds, LIGHT Res Inst, Fac Med & Hlth, Leeds, W Yorkshire, England. [Halperin, Eran] Tel Aviv Univ, Blavatnik Sch Comp Sci, IL-69978 Tel Aviv, Israel. [Halperin, Eran] Tel Aviv Univ, Dept Mol Microbiol & Biotechnol, IL-69978 Tel Aviv, Israel. [Halperin, Eran] Int Comp Sci Inst, Berkeley, CA 94704 USA. [Hengstenberg, Christian] Univ Regensburg, Klin & Poliklin Innere Med 2, Regensburg, Germany. [Laaksonen, Reijo] Tampere Univ Hosp, Ctr Sci, Tampere, Finland. [Li, Mingyao] Univ Penn, Philadelphia, PA 19104 USA. [Maerz, Winfried] Synlab Ctr, Lab Diagnost Heidelberg, Heidelberg, Germany. [Maerz, Winfried] Med Univ Graz, Inst Clin Med, Graz, Austria. [Maerz, Winfried] Med Univ Graz, Chem Lab Diagnost, Graz, Austria. [Maerz, Winfried] Univ Heidelberg, Inst Publ Hlth Social & Prevent Med, Fac Med Mannheim, Heidelberg, Germany. [Musunuru, Kiran; Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiac Unit, Boston, MA 02114 USA. [Musunuru, Kiran; Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Musunuru, Kiran; Voight, Benjamin F.; Kathiresan, Sekar] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Voight, Benjamin F.; Kathiresan, Sekar] MIT, Program Med & Populat Genet, Cambridge, MA 02139 USA. [Musunuru, Kiran; Voight, Benjamin F.; Kathiresan, Sekar] MIT, Broad Inst Harvard, Cambridge, MA 02139 USA. [Burnett, Mary Susan; Epstein, Stephen E.] Washington Hosp Ctr, Cardiovasc Res Inst, MedStar Res Inst, Washington, DC 20010 USA. [O'Donnell, Christopher J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Rader, Daniel J.; Reilly, Muredach P.] Univ Penn, Sch Med, Inst Translat Med & Therapeut, Philadelphia, PA 19104 USA. [Rader, Daniel J.; Reilly, Muredach P.] Univ Penn, Cardiovasc Inst, Philadelphia, PA 19104 USA. [Voight, Benjamin F.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Univ Leicester, Dept Cardiovasc Sci, Glenfield Hosp, Leicester, Leics, England. RP Schunkert, H (reprint author), Univ Lubeck, Med Klin 2, Ratzeburger Allee 160, D-23538 Lubeck, Germany. EM njs@le.ac.uk; heribert.schunkert@uk-sh.de RI Voight, Benjamin/F-1775-2011; Stewart, Alexandre/A-5677-2011; Laaksonen, Reijo/D-6323-2014; Konig, Inke/A-4544-2009; Erdmann, Jeanette/A-4417-2009; Erdmann, Jeanette/P-7513-2014 OI Ziegler, Andreas/0000-0002-8386-5397; Cupples, L. Adrienne/0000-0003-0273-7965; Stewart, Alexandre/0000-0003-2673-9164; Erdmann, Jeanette/0000-0002-4486-6231 FU Reynold's Foundation; National Heart, Lung, and Blood Institute (NHLBI) [HL087647]; Boehringer Ingelheim; PHILIPS Medical Systems; Government of Rheinland-Pfalz; Johannes-Gutenberg University of Mainz; Fondation de France, the French Ministry of Research; Institut National de la Sante et de la Recherche Medicale; National Institutes of Health (NIH) NHLBI [R01HL089650-02]; Deutsche Forschungsgemeinschaft; German Federal Ministry of Education and Research (BMBF); German National Genome Research Network; European Union (EU) [LSHM-CT-2006-037593, LSHM-CT-2004-503485, HEALTH-F2-2008-201668]; German Federal Ministry of Education and Research; Sanofi/Aventis; Roche; Dade Behring/Siemens; AstraZeneca; US NIH; NHLBI; Broad Institute Center for Genotyping and Analysis; National Center for Research Resources [U54 RR020278]; Cardiovascular Institute of the University of Pennsylvania; MedStar Research Institute; Washington Hospital Center; GlaxoSmithKline; University of Pennsylvania School of Medicine; Canadian Institutes of Health Research (CIHR) [MOP82810, MOP172605, MOP77682]; Canadian Funds for Innovation (CFI) [11966]; Heart and Stroke Foundation of Ontario [NA6001]; Wellcome Trust; BHF; UK Medical Research Council; Leicester National Institute of Health Research Biomedical Research Unit in Cardiovascular Disease; NGFNplus; BMBF; NIH/National Human Genome Research Institute (NHGRI); NIH/NHLBI; National Cancer Institute Division of Cancer Epidemiology and Genetics; Heart & Stroke Funds Ontario; CFI; Cystic Fibrosis Foundation; Cancer Immunology and Hematology Branch; Institute for Biomedical Sciences, Academia Sinica, Taipei, Taiwan; Academia Sinica; Pfizer; CIHR; [R01HG004517] FX The ADVANCE study was supported by a grant from the Reynold's Foundation and National Heart, Lung, and Blood Institute (NHLBI) grant HL087647. Genetic analyses of CADomics were supported by a research grant from Boehringer Ingelheim. Recruitment and analysis of the CADomics cohort was supported by grants from Boehringer Ingelheim and PHILIPS Medical Systems; by the Government of Rheinland-Pfalz in the context of the "Stiftung Rheinland-Pfalz fur Innovation"; by the research program "Wissen schafft Zukunft"; by the Johannes-Gutenberg University of Mainz in the context of the "Schwerpunkt Vaskulare Pravention" and the "MAIFOR grant 2001"; and by grants from the Fondation de France, the French Ministry of Research, and the Institut National de la Sante et de la Recherche Medicale.; The deCODE CAD/MI Study was sponsored by National Institutes of Health (NIH) NHLBI grant R01HL089650-02. The GerMIFS I-III (KORA) were supported by the Deutsche Forschungsgemeinschaft and the German Federal Ministry of Education and Research (BMBF) in the context of the German National Genome Research Network (NGFN-2 and NGFN-plus) and the European Union (EU)-funded integrated project Cardiogenics (LSHM-CT-2006-037593). The KORA research platform was initiated and financed by the GSF-National Research Centre for Environment and Health, which is funded by the German Federal Ministry of Education and Research and of the State of Bavaria. LURIC has received funding from the EU framework 6-funded Integrated Project "Bloodomics" (LSHM-CT-2004-503485); from the EU framework 7-funded Integrated Project AtheroRemo (HEALTH-F2-2008-201668); and from Sanofi/Aventis, Roche, Dade Behring/Siemens, and AstraZeneca. The MIGen study was funded by the US NIH and NHLBI's STAMPEED genomics research program, and genotyping was partially funded by The Broad Institute Center for Genotyping and Analysis, which is supported by grant U54 RR020278 from the National Center for Research Resources. Recruitment of PennCATH was supported by the Cardiovascular Institute of the University of Pennsylvania. Recruitment of the MedStar sample was supported in part by the MedStar Research Institute and the Washington Hospital Center and a research grant from GlaxoSmithKline. Genotyping of PennCATH and MedStar was performed at the Center for Applied Genomics at the Children's Hospital of Philadelphia and supported by GlaxoSmithKline through an Alternate Drug Discovery Initiative research alliance award (to Drs Reilly and Rader) with the University of Pennsylvania School of Medicine. The OHGS was supported by Canadian Institutes of Health Research (CIHR) #MOP82810 (to Dr Roberts), Canadian Funds for Innovation (CFI) #11966 (to Dr Roberts), Heart and Stroke Foundation of Ontario #NA6001 (to Dr McPherson), CIHR #MOP172605 (to Dr McPherson), and CIHR #MOP77682 (to Dr Stewart). The WTCCC study was funded by the Wellcome Trust. Recruitment of cases for the WTCCC study was carried out by the British Heart Foundation (BHF) Family Heart Study Research Group and supported by the BHF and the UK Medical Research Council. Dr Samani holds a chair funded by the BHF. Dr Samani also is supported by the Leicester National Institute of Health Research Biomedical Research Unit in Cardiovascular Disease.; Dr Absher reports receiving an NIH research grant for the ADVANCE study. Dr Assimes reports receiving an NIH research grant for the ADVANCE study. Dr Blankenberg reports receiving research grants from NGFNplus for Atherogenomics and from BMBF for CADomics. Dr Boerwinkle received research support from NIH/National Human Genome Research Institute (NHGRI), GWA for gene-environment interaction effects influencing CGD; NIH/NHLBI, Molecular epidemiology of essential hypertension; NIH/NHLBI, Genome-wide association for loci influencing coronary heart disease; NIH/NHLBI, Genetics of hypertension-associated treatment; NIH/NHLBI, Modeling DNA diversity in reverse cholesterol transport; NIH/NHLBI, 20-year changes in fitness and cardiovascular disease risk; NIH/NHLBI, Genetic epidemiology of sodium-lithium countertransport; NIH/National Institute of General Medical Sciences (NIGMS), Pharmacogenomic evaluation of antihypertensive responses; NIH/NIGMS, Genomic approaches to common chronic disease; NIH/NHLBI, Genes of the CYP450-derived eicosanoids in subclinical atherosclerosis; NIH/NHGRI-University of North Carolina, Chapel Hill, Genetic epidemiology of causal variants across the life course; and NIH/NHLBI, Building on GWAS for NHLBI-diseases: the CHARGE consortium. Dr Cupples reports receiving research grants from NIH/NHLBI, The Framingham Heart Study; NIH/NHLBI, Genome-wide association study of cardiac structure and function; NIH/NHLBI, Functional evaluation of GWAS loci for cardiovascular intermediate phenotypes; and NIH/NHLBI, Building on GWAS for NHLBI-diseases: the CHARGE consortium. Dr Halperin reports receiving research grants from NIH, subcontract Genome-wide association study of Non Hodgkin's lymphoma; ISF, Efficient design and analysis of disease association studies; EU, consultant AtheroRemo; NSF, Methods for sequencing based associations; BSF, Searching for causal genetic variants in breast cancer and honoraria from Scripps Institute, UCLA. Dr Halperin also reports ownership interest in Navigenics. Dr Hengstenberg reports receiving research grants for EU Cardiogenics. Dr Holm reports receiving a research grant from NIH; providing expert witness consultation for the district court of Reykjavik; serving as member of the editorial board for decodeme, a service provided by deCODE Genetics; and employment with deCODE Genetics. Dr Li reports receiving research grant R01HG004517 and other research support in the form of coinvestigator on several NIH-funded grants and receiving honoraria from National Cancer Institute Division of Cancer Epidemiology and Genetics. Dr McPherson reports receiving research grants from Heart & Stroke Funds Ontario, CIHR, and CFI. Dr Rader reports receiving research grant support from GlaxoSmithKline. Dr Roberts reports receiving research grants from the Cystic Fibrosis Foundation, NIH, and Cancer Immunology and Hematology Branch; membership on the speakers bureau for AstraZeneca; receiving honoraria from Several; and serving as consultant/advisory board member for Celera. Dr Stewart reports receiving research grant support from CIHR, Genome-wide scan to identify coronary artery disease genes, and CIHR, Genetic basis of salt-sensitive hypertension in humans; other research support from CFI: Infrastructure support; and honoraria from the Institute for Biomedical Sciences, Academia Sinica, Taipei, Taiwan. Dr Thorleifsson is an employee of deCODE Genetics.; Dr Thorsteinsdottir reports receiving research grants from NIH and EU; serving as an expert witness for a US trial; having stock options at deCODE Genetics; and havng employment with deCODE Genetics. Dr Kathiresan reports receiving research grants from Pfizer, Discovery of type 2 diabetes genes, and Alnylam, Function of new lipid genes, and serving as consultant/advisory board member for DAIICHI SANKYO Merck. Dr Reilly reports receiving research grant support from GlaxoSmithKline. Dr Schunkert reports receiving research grants from the EU, project Cardiogenics; NGFN, project Atherogenomics; and CADnet BMBF. M. Preuss, L. Chen, and Drs Knig, Thompson, Erdmann, Hall, Laaksonen, Murz, Musunuru, Nelson, Burnett, Epstein, O'Donnell, Quertermous, Schillert, Stefansson, Voight, Wells, Ziegler, and Samani have no conflicts to disclose.; Genotyping of PennCATH and MedStar was supported by GlaxoSmithKline. Dawn M. Waterworth, Max C. Walker, and Vincent Mooser are employees of GlaxoSmithKline. PennCath/MedStar investigators acknowledge the support of Eliot Ohlstein, Dan Burns and Allen Roses at GlaxoSmithKline. NR 20 TC 89 Z9 92 U1 1 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1942-325X J9 CIRC-CARDIOVASC GENE JI Circ.-Cardiovasc. Genet. PD OCT PY 2010 VL 3 IS 5 BP 475 EP U186 DI 10.1161/CIRCGENETICS.109.899443 PG 31 WC Cardiac & Cardiovascular Systems; Genetics & Heredity SC Cardiovascular System & Cardiology; Genetics & Heredity GA 666ZX UT WOS:000283163100012 PM 20923989 ER PT J AU El Sahly, HM Patel, SM Atmar, RL Lanford, TA Dube, T Thompson, D Sim, BKL Long, C Keitel, WA AF El Sahly, H. M. Patel, S. M. Atmar, R. L. Lanford, T. A. Dube, T. Thompson, D. Sim, B. K. L. Long, C. Keitel, W. A. TI Safety and Immunogenicity of a Recombinant Nonglycosylated Erythrocyte Binding Antigen 175 Region II Malaria Vaccine in Healthy Adults Living in an Area Where Malaria Is Not Endemic SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID APICAL MEMBRANE ANTIGEN-1; PLASMODIUM-FALCIPARUM; INHIBITORY ANTIBODIES; INVASION PATHWAYS; CLINICAL MALARIA; STAGE; PROTECTION; ELICITS; PROTEIN; DOMAIN AB Erythrocyte binding antigen region II (EBA-175) is a conserved antigen of Plasmodium falciparum that is involved in binding of the parasite to the host's erythrocytes. We evaluated the safety and immunogenicity of a recombinant EBA-175 vaccine with aluminum phosphate adjuvant in healthy young adults living in the United States. Eighteen subjects/group received ascending doses (5, 20, 80, or 160 mu g) of the vaccine at 0, 1, and 6 months; 8 subjects received placebo. Most of the injection site and systemic reactions were mild to moderate in intensity. After 2 or 3 doses of the vaccine at any concentration, antibody levels measured by enzyme-linked immunosorbent assay were significantly higher than those for the placebo group. Sera from subjects who received 3 doses of the vaccine at any concentration inhibited the growth of erythrocyte-stage P. falciparum at low levels compared to sera from placebo recipients or preimmune sera. In conclusion, the EBA-175 vaccine with adjuvant was safe and immunogenic in malaria-naive subjects. C1 [El Sahly, H. M.; Patel, S. M.; Atmar, R. L.; Lanford, T. A.; Keitel, W. A.] Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. [El Sahly, H. M.; Patel, S. M.; Atmar, R. L.; Keitel, W. A.] Baylor Coll Med, Dept Med, Infect Dis Sect, Houston, TX 77030 USA. [Long, C.] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. [Dube, T.; Thompson, D.] EMMES Corp, Rockville, MD USA. [Sim, B. K. L.] Prot Potential LLC, Rockville, MD USA. RP El Sahly, HM (reprint author), Baylor Coll Med, Dept Mol Virol & Microbiol, 1 Baylor Plaza,BCM-MS280, Houston, TX 77030 USA. EM hanae@bcm.edu FU PATH/Malaria Vaccine Initiative; National Institute of Allergy and Infectious Diseases [N01-AI-25465] FX The GIA Reference Center is supported by the PATH/Malaria Vaccine Initiative. Funding for this project was provided by the National Institute of Allergy and Infectious Diseases (contract N01-AI-25465 to W. A. Keitel) and, in part, by the Intramural Program of the National Institute of Allergy and Infectious Diseases. NR 42 TC 31 Z9 31 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1556-6811 J9 CLIN VACCINE IMMUNOL JI Clin. Vaccine Immunol. PD OCT PY 2010 VL 17 IS 10 BP 1552 EP 1559 DI 10.1128/CVI.00082-10 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 675TN UT WOS:000283858700009 PM 20702657 ER PT J AU Krolewiecki, AJ Ramanathan, R Fink, V McAuliffe, I Cajal, SP Won, K Juarez, M Di Paolo, A Tapia, L Acosta, N Lee, R Lammie, P Abraham, D Nutman, TB AF Krolewiecki, Alejandro J. Ramanathan, Roshan Fink, Valeria McAuliffe, Isabel Cajal, Silvana P. Won, Kimberly Juarez, Marisa Di Paolo, Adriana Tapia, Laura Acosta, Norma Lee, Rogan Lammie, Patrick Abraham, David Nutman, Thomas B. TI Improved Diagnosis of Strongyloides stercoralis Using Recombinant Antigen-Based Serologies in a Community-Wide Study in Northern Argentina SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID LUCIFERASE IMMUNOPRECIPITATION SYSTEMS; INFECTION; SEROEPIDEMIOLOGY; SPECIFICITY; SENSITIVITY; POPULATION; ASSAY AB The serodiagnosis of Strongyloides stercoralis infection by enzyme-linked immunosorbent assays based on crude antigen (CrAg-ELISA), while useful, has been limited by the reliance on crude parasite extracts. Newer techniques such as the luciferase immunoprecipitation system assay (LIPS), based on a 31-kDa recombinant antigen (termed NIE) from S. stercoralis and/or the recombinant antigen S. stercoralis immunoreactive antigen (SsIR), or the NIE-ELISA have shown promise in controlled settings. We compared each of these serologic assays in individuals from both regions of the world in which S. stercoralis is endemic and those in which it is not. A comprehensive stool evaluation (sedimentation concentration, Baermann concentration with charcoal cultures, agar plate, and Harada-Mori) and four different serologic techniques using CrAg-ELISA or recombinant NIE-ELISA as well as LIPS using NIE alone or in combination with a second recombinant antigen (NIE/SsIR-LIPS) were compared among individuals with parasitologically proven infection (n = 251) and healthy controls from regions of the world in which the infection is nonendemic (n = 11). Accuracy was calculated for each assay. The prevalence of S. stercoralis infection was 29.4% among Argentinean stool samples (n = 228). Sedimentation concentration and Baermann were the most sensitive stool-based methods. NIE-LIPS showed the highest sensitivity (97.8%) and specificity (100%) of the serologic assays. The calculated negative predictive value was highest for both the NIE-LIPS and CrAg-ELISA (>97%) irrespective of disease prevalence. No cross-reactivity with soil-transmitted helminths was noted. NIE-LIPS compares favorably against the current CrAg-ELISA and stool evaluation, providing additional accuracy and ease of performance in the serodiagnosis of S. stercoralis infections irrespective of disease prevalence. C1 [Krolewiecki, Alejandro J.; Fink, Valeria] Fdn Huesped, Area Invest Clin, Buenos Aires, DF, Argentina. [Ramanathan, Roshan; Nutman, Thomas B.] NIAID, Clin Parasitol Unit, Bethesda, MD 20892 USA. [Ramanathan, Roshan; Nutman, Thomas B.] NIAID, Helminth Immunol Sect, Parasit Dis Lab, Bethesda, MD 20892 USA. [McAuliffe, Isabel; Won, Kimberly; Lammie, Patrick] US Ctr Dis Control & Prevent, CGH, DPDM, PDB, Atlanta, GA 30341 USA. [Krolewiecki, Alejandro J.; Cajal, Silvana P.; Juarez, Marisa; Di Paolo, Adriana; Acosta, Norma] Univ Nacl Salta, Inst Invest Enfermedades Trop, San Ramon Nueva Oran, Salta, Argentina. [Tapia, Laura] Hosp San Vicente Paul, San Ramon Nueva Oran, Salta, Argentina. [Lee, Rogan] Westmead Hosp, ICPMR, Parasitol Unit, Westmead, NSW 2145, Australia. [Abraham, David] Thomas Jefferson Univ, Dept Microbiol & Immunol, Kimmel Canc Ctr, Philadelphia, PA 19107 USA. RP Krolewiecki, AJ (reprint author), Pje Angel Peluffo 3932,C1202ABB, Buenos Aires, DF, Argentina. EM alekrol@huesped.org.ar NR 29 TC 46 Z9 48 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1556-6811 J9 CLIN VACCINE IMMUNOL JI Clin. Vaccine Immunol. PD OCT PY 2010 VL 17 IS 10 BP 1624 EP 1630 DI 10.1128/CVI.00259-10 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 675TN UT WOS:000283858700019 PM 20739501 ER PT J AU Gattinoni, L Ji, Y Restifo, NP AF Gattinoni, Luca Ji, Yun Restifo, Nicholas P. TI Wnt/beta-Catenin Signaling in T-Cell Immunity and Cancer Immunotherapy SO CLINICAL CANCER RESEARCH LA English DT Article ID TRANSCRIPTION FACTOR GATA-3; MEMORY STEM-CELLS; BETA-CATENIN; IN-VIVO; WNT PATHWAY; ADOPTIVE IMMUNOTHERAPY; MOLECULAR SWITCH; EFFECTOR; DIFFERENTIATION; SURVIVAL AB Wnt ligands are lipid-modified secreted glycoproteins that regulate embryonic development, cell fate specification, and the homeostasis of self-renewing adult tissues. In addition to its well-established role in thymocyte development, recent studies have indicated that Wnt/beta-catenin signaling is critical for the differentiation, polarization, and survival of mature T lymphocytes. Here, we describe our current understanding of Wnt signaling in the biology of post-thymic T cells, and discuss how harnessing the Wnt/beta-catenin pathway might improve the efficacy of vaccines, T-cell-based therapies, and allogeneic stem cell transplantation for the treatment of patients with cancer. Clin Cancer Res; 16( 19); 4695-701. (C) 2010 AACR. C1 [Gattinoni, Luca; Ji, Yun; Restifo, Nicholas P.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Restifo, NP (reprint author), NCI, Ctr Canc Res, NIH, Bldg 10,Room 3-6257, Bethesda, MD 20892 USA. EM restifo@nih.gov RI Gattinoni, Luca/A-2281-2008; Ji, Yun/B-7245-2009; Restifo, Nicholas/A-5713-2008; OI Gattinoni, Luca/0000-0003-2239-3282; Ji, Yun/0000-0001-6340-7009; Restifo, Nicholas P./0000-0003-4229-4580 FU NIH, National Cancer Institute, Center for Cancer Research FX Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 69 TC 37 Z9 40 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 EI 1557-3265 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT 1 PY 2010 VL 16 IS 19 BP 4695 EP 4701 DI 10.1158/1078-0432.CCR-10-0356 PG 7 WC Oncology SC Oncology GA 660MO UT WOS:000282647900003 PM 20688898 ER PT J AU Pastorino, F Loi, M Sapra, P Becherini, P Cilli, M Emionite, L Ribatti, D Greenberger, LM Horak, ID Ponzoni, M AF Pastorino, Fabio Loi, Monica Sapra, Puja Becherini, Pamela Cilli, Michele Emionite, Laura Ribatti, Domenico Greenberger, Lee M. Horak, Ivan D. Ponzoni, Mirco TI Tumor Regression and Curability of Preclinical Neuroblastoma Models by PEGylated SN38 (EZN-2208), a Novel Topoisomerase I Inhibitor SO CLINICAL CANCER RESEARCH LA English DT Article ID HIGH-RISK NEUROBLASTOMA; REFRACTORY SOLID TUMORS; THERAPEUTIC-EFFICACY; XENOGRAFT MODELS; PHASE-II; LIPOSOMAL CHEMOTHERAPY; IRINOTECAN CPT-11; CANCER; ANGIOGENESIS; TOPOTECAN AB Purpose: Treatment of neuroblastoma is successful in less than half of patients with high-risk disease. The antitumor activity of a water soluble pegylated SN38 drug conjugate, EZN-2208, was compared with CPT-11 (a prodrug for SN38) in preclinical models of human neuroblastoma. Experimental Design: The in vitro cytotoxicity of EZN-2208 was tested by counting trypan blue dye- and Annexin V-positive cells, whereas its therapeutic efficacy was evaluated, in terms of survival, and antitumor and antiangiogenic activities, in s.c. luciferase-transfected, pseudometastatic, and orthotopic neuroblastoma animal models. Results: EZN-2208 was about 100-fold more potent than CPT-11 in vitro, by inducing apoptosis/necrosis and p53 expression and by reducing hypoxia-inducible factor (HIF)-1 alpha/HIF-2 alpha expression. EZN-2208 gave superior antitumor effects compared with CPT-11 in neuroblastoma xenografts. EZN-2208 treatment always resulted in lack of tumor detection at the end of trials whereas only small therapeutic effects were observed with CPT-11, as assessed by luciferase assay or tumor size, or even by staining histologic sections of tumors with antibodies recognizing neuroblastoma cells and cell proliferation. In a neuroblastoma model resistant to doxorubicin, cisplatin, vincristine, fenretinide, and topotecan, EZN-2208 induced 100% curability. It also blocked tumor relapse after topotecan-vincristine-doxorubicin combined treatment. Mechanistic experiments showed statistically significantly enhanced terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling and Histone H2ax staining as well as decreased vascular endothelial growth factor, CD31, matrix metalloproteinase (MMP)-2, and MMP-9 expression in tumors removed from EZN-2208-treated mice and radiating vessels invading the tumor implanted onto the chorioallantoic membranes. Conclusions: EZN-2208 should be considered a most promising novel antineuroblastoma agent. An ongoing phase I study in pediatric patients should identify the optimal dose for a phase II study. Clin Cancer Res; 16(19); 4809-21. (C) 2010 AACR. C1 [Pastorino, Fabio; Loi, Monica; Becherini, Pamela; Ponzoni, Mirco] G Gaslini Childrens Hosp, Expt Therapies Unit, Lab Oncol, I-16148 Genoa, Italy. [Cilli, Michele; Emionite, Laura] Natl Canc Inst, Anim Res Facil, Genoa, Italy. [Sapra, Puja; Greenberger, Lee M.; Horak, Ivan D.] Enzon Pharmaceut, Piscataway, NJ USA. [Ribatti, Domenico] Univ Bari, Dept Human Anat, Bari, Italy. RP Pastorino, F (reprint author), G Gaslini Childrens Hosp, Expt Therapy Unit, Lab Oncol, I-16148 Genoa, Italy. EM fabiopastorino@ospedale-gaslini.ge.it RI Ponzoni, Mirco/J-7713-2016 OI Ponzoni, Mirco/0000-0002-6164-4286 FU Enzon Phamaceuticals; Associazione Italiana per la Ricerca sul Cancro (AIRC, MFAG and IG); Fondazione Italiana per la Lotta al Neuroblastoma FX Enzon Phamaceuticals, Associazione Italiana per la Ricerca sul Cancro (AIRC, MFAG and IG), and the Fondazione Italiana per la Lotta al Neuroblastoma. NR 50 TC 36 Z9 38 U1 1 U2 14 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 OCT 1 PY 2010 VL 16 IS 19 BP 4809 EP 4821 DI 10.1158/1078-0432.CCR-10-1354 PG 13 WC Oncology SC Oncology GA 660MO UT WOS:000282647900014 PM 20702613 ER PT J AU Hong, JJ Rosenberg, SA Dudley, ME Yang, JC White, DE Butman, JA Sherry, RM AF Hong, Jenny J. Rosenberg, Steven A. Dudley, Mark E. Yang, James C. White, Donald E. Butman, John A. Sherry, Richard M. TI Successful Treatment of Melanoma Brain Metastases with Adoptive Cell Therapy SO CLINICAL CANCER RESEARCH LA English DT Article ID INFILTRATING LYMPHOCYTE-CULTURES; GAMMA-KNIFE RADIOSURGERY; CANCER REGRESSION; MALIGNANT-MELANOMA; AUTOIMMUNITY; RADIOTHERAPY; MANAGEMENT; ANTIGEN AB Purpose: To determine the objective response rate and response duration of melanoma brain metastases to adoptive cell therapy (ACT) with autologous antitumor lymphocytes plus interleukin-2 following a lymphodepleting preparative regimen. Methods: Between 2000 and 2009, 264 patients with metastatic melanoma received ACT, consisting of cyclophosphamide and fludarabine with or without total body irradiation, followed by the infusion of autologous tumor-infiltrating lymphocytes (TIL) or autologous peripheral blood lymphocytes retrovirally transduced to express a T-cell receptor (TCR) that recognized the melanocyte differentiation antigens gp-100 or MART-1. From this group, 26 patients were retrospectively identified to have had untreated brain metastases and extracranial disease before receiving ACT. The response rate and duration of melanoma brain metastases, as well as the overall response rate, response duration, and survival for these patients, are presented. Results: Seventeen of these 26 patients received ACT with TIL. Seven of these patients (41%) achieved a complete response in the brain, and six patients achieved an overall partial response. In the nine patients that received TCR-transduced lymphocytes, two patients achieved a complete response in the brain (22%) and one of these two achieved an overall partial response. One patient developed a tumor-associated subarachnoid hemorrhage during the thrombocytopenic phase of therapy and had an uneventful metastatectomy. Conclusion: ACT with a nonmyeloablative preparative regimen using either TIL- or TCR gene-transduced cells and interleukin-2 can mediate complete and durable regression of melanoma brain metastases. This strategy can be used safely in selected patients with metastatic melanoma to the brain. Clin Cancer Res; 16(19); 4892-8. (C) 2010 AACR. C1 [Sherry, Richard M.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. [Butman, John A.] NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Sherry, RM (reprint author), NCI, Surg Branch, NIH, 10 Ctr Dr,MSC 1201,CRC 3-5942, Bethesda, MD 20892 USA. EM sherryr@mail.nih.gov RI Butman, John/A-2694-2008; Butman, John/J-2780-2013 OI Butman, John/0000-0002-1547-9195 NR 26 TC 67 Z9 70 U1 0 U2 5 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 OCT 1 PY 2010 VL 16 IS 19 BP 4892 EP 4898 DI 10.1158/1078-0432.CCR-10-1507 PG 7 WC Oncology SC Oncology GA 660MO UT WOS:000282647900022 PM 20719934 ER PT J AU Vickers, KC Palmisano, BT Remaley, AT AF Vickers, Kasey C. Palmisano, Brian T. Remaley, Alan T. TI The Role of Noncoding "Junk DNA" in Cardiovascular Disease SO CLINICAL CHEMISTRY LA English DT Editorial Material C1 [Vickers, Kasey C.; Palmisano, Brian T.; Remaley, Alan T.] NHLBI, NIH, Pulm & Vasc Med Branch, Lipoprot Metab Sect, Bethesda, MD 20892 USA. RP Remaley, AT (reprint author), NHLBI, NIH, Pulm & Vasc Med Branch, Lipoprot Metab Sect, Bldg 10,Rm 7N-115,10 Ctr Dr, Bethesda, MD 20892 USA. EM aremaley@cc.nih.gov OI Palmisano, Brian T./0000-0002-2140-1060 NR 5 TC 1 Z9 2 U1 0 U2 9 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 OCT PY 2010 VL 56 IS 10 BP 1518 EP 1520 DI 10.1373/clinchem.2010.147603 PG 3 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 655SL UT WOS:000282269700003 PM 20639473 ER PT J AU Lin, JP Vitek, L Schwertner, HA AF Lin, Jing-Ping Vitek, Libor Schwertner, Harvey A. TI Serum Bilirubin and Genes Controlling Bilirubin Concentrations as Biomarkers for Cardiovascular Disease SO CLINICAL CHEMISTRY LA English DT Review ID CORONARY-ARTERY-DISEASE; HEME OXYGENASE-1 GENE; ISCHEMIC-HEART-DISEASE; SINGLE NUCLEOTIDE POLYMORPHISMS; GENOME-WIDE ASSOCIATION; ALBUMIN-BOUND BILIRUBIN; LOW-DENSITY-LIPOPROTEIN; CRIGLER-NAJJAR-SYNDROME; GILBERTS-SYNDROME; MICROSATELLITE POLYMORPHISM AB BACKGROUND: Serum bilirubin has been consistently shown to be inversely related to cardiovascular disease (CVD). Recent studies showed serum bilirubin to be associated with CVD-related factors such as diabetes, metabolic syndrome, and body mass index. Although the association of serum bilirubin with CVD has been found in both retrospective and prospective studies, less information is available on the role of genes that control bilirubin concentrations and their association with CVD. CONTENT: In this review, we provide detailed information on the identity of the major genes that control bilirubin concentrations and their association with serum bilirubin concentrations and CVD risk. We also update the results of the major studies that have been performed on the association between serum bilirubin, CVD, and CVD-related diseases such as diabetes or metabolic syndrome. Studies consistently indicate that bilirubin concentrations are inversely associated with different types of CVD and CVD-related diseases. A conditional linkage study indicates that UGT1A1 is the major gene controlling serum bilirubin concentrations, and this finding has been confirmed in recent genomewide association studies. Studies also indicate that individuals homozygous for UGT1A1*28 have a significantly lower risk of developing CVD than carriers of the wild-type alleles. SUMMARY: Serum bilirubin has a protective effect on CVD and CVD-related diseases, and UGT1A1 is the major gene controlling serum bilirubin concentrations. Pharmacologic, nonpharmacologic, or genetic interventions that increase serum bilirubin concentrations could provide more direct evidence on the role of bilirubin in CVD prevention. (c) 2010 American Association for Clinical Chemistry C1 [Schwertner, Harvey A.] Wilford Hall USAF Med Ctr, San Antonio, TX 78236 USA. [Lin, Jing-Ping] NHLBI, Off Biostat Res, Div Cardiovasc Sci, NIH, Bethesda, MD 20892 USA. [Vitek, Libor] Charles Univ Prague, Dept Internal Med 4, Fac Med 1, Prague, Czech Republic. [Vitek, Libor] Charles Univ Prague, Inst Clin Biochem & Lab Diagnost, Fac Med 1, Prague, Czech Republic. RP Schwertner, HA (reprint author), Wilford Hall USAF Med Ctr, 2200 Bergquist Dr, San Antonio, TX 78236 USA. EM harvey.schwertner@lackland.af.mil RI Vitek, Libor/A-2645-2008 OI Vitek, Libor/0000-0002-5318-0151 FU Czech Ministry of Education [MSM 0021620807, ME849]; Czech Ministry of Health [NS 9770-4-28] FX Research Funding: L. Vitek, grants MSM 0021620807 and ME849 from the Czech Ministry of Education and NS 9770-4-28 from the Czech Ministry of Health. NR 79 TC 64 Z9 66 U1 1 U2 4 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 OCT PY 2010 VL 56 IS 10 BP 1535 EP 1543 DI 10.1373/clinchem.2010.151043 PG 9 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 655SL UT WOS:000282269700009 PM 20693308 ER PT J AU Odgerel, Z van der Ven, PFM Furst, DO Goldfarb, LG AF Odgerel, Zagaa van der Ven, Peter F. M. Fuerst, Dieter O. Goldfarb, Lev G. TI DNA sequencing errors in molecular diagnostics of filamin myopathy SO CLINICAL CHEMISTRY AND LABORATORY MEDICINE LA English DT Article DE filamin C (FLNC) gene; filaminopathy; mutation-screening; myofibrillar myopathy; pseudogene ID Z-DISC; MUSCLE; PROTEIN; DIMERIZATION; PHENOTYPE; INTERACTS; MYOTILIN; ISOFORM; FLNC AB Background: Filamin myopathy is a neuromuscular disorder manifesting with predominantly limb-girdle muscle weakness and in many patients with diaphragm paralysis and cardiomyopathy, caused by mutations in the filamin C (FLNC) gene. Molecular diagnosis of filamin myopathy based on direct DNA sequencing of coding exons is compromised by the presence of a high homology pseudogene (pseFLNC) located approximately 53.6 kb downstream of the functional FLNC gene on chromosome 7q. Methods: Molecular cloning, RT-PCR and real-time PCR methods were used to detect sequence differences between the FLNC and pseFLNC that are implicated in known or potential molecular diagnostic errors. Overall, 50 patients with a phenotype resembling filamin myopathy have been screened for mutations in FLNC. Results: FLNC sequence inconsistencies caused by the interference from pseFLNC were identified and diagnostic errors involving, in particular, the detection of the most frequent disease-causing FLNC p.W2710X mutation resolved. Mismatches between the FLNC and pseFLNC sequences were tabulated for future use. Conclusions: We devise a strategy that allows one to discern mutations occurring in the functional FLNC from those harbored in pseFLNC, thus preventing possible complications in future research and patient genetic testing. Clin Chem Lab Med 2010;48:1409-14. C1 [Odgerel, Zagaa; Goldfarb, Lev G.] Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD 20892 USA. [van der Ven, Peter F. M.; Fuerst, Dieter O.] Univ Bonn, Dept Mol Cell Biol, Inst Cell Biol, D-5300 Bonn, Germany. RP Goldfarb, LG (reprint author), Natl Inst Neurol Disorders & Stroke, NIH, Room 4S06,5625 Fishers Lane,MSC 9404, Bethesda, MD 20892 USA. EM GoldfarbL@ninds.nih.gov FU National Institute of Neurological Disorders and Stroke, National Institutes of Health; German Research Foundation [DFG/FOR1228]; German Ministry of Education and Research (BMBF) FX This work was supported in part by the Intramural Research Program of the National Institute of Neurological Disorders and Stroke, National Institutes of Health (Z.O. and L.G.G.) and the German Research Foundation (DFG/FOR1228). D.O.F. and P.F.M.v.d.V are members of the German muscular dystrophy network (MD-NET 2) funded by the German Ministry of Education and Research (BMBF). NR 21 TC 8 Z9 8 U1 0 U2 0 PU WALTER DE GRUYTER & CO PI BERLIN PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY SN 1434-6621 J9 CLIN CHEM LAB MED JI Clin. Chem. Lab. Med. PD OCT PY 2010 VL 48 IS 10 BP 1409 EP 1414 DI 10.1515/CCLM.2010.272 PG 6 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 667IJ UT WOS:000283186200008 PM 20578970 ER PT J AU Solomon, BD Bous, SM Bianconi, S Pineda-Alvarez, DE AF Solomon, Benjamin D. Bous, Sophia M. Bianconi, Simona Pineda-Alvarez, Daniel E. TI Consideration of VACTERL association in patients with trisomy 21 SO CLINICAL DYSMORPHOLOGY LA English DT Article ID DOWN-SYNDROME C1 [Solomon, Benjamin D.; Bous, Sophia M.; Pineda-Alvarez, Daniel E.] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. [Bianconi, Simona] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Endocrinol & Genet, NIH, Bethesda, MD USA. RP Solomon, BD (reprint author), NHGRI, Med Genet Branch, NIH, Bldg 35,Room 1B-207, Bethesda, MD 20892 USA. EM solomonb@mail.nih.gov FU Division of Intramural Research, National Human Genome Research Institute, National Institutes of Health, Department of Health and Human Services, USA FX This study was supported by the Division of Intramural Research, National Human Genome Research Institute, National Institutes of Health, Department of Health and Human Services, USA. The authors thank the patients and families involved, and they also thank Dr Maximilian Muenke for his support and mentorship. NR 6 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0962-8827 J9 CLIN DYSMORPHOL JI Clin. Dysmorphol. PD OCT PY 2010 VL 19 IS 4 BP 209 EP 211 DI 10.1097/MCD.0b013e32833b2b9c PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 648EG UT WOS:000281672600009 PM 20512033 ER PT J AU Yuan, LP Santi, M Rushing, EJ Cornelison, R MacDonald, TJ AF Yuan, Liangping Santi, Mariarita Rushing, Elisabeth J. Cornelison, Robert MacDonald, Tobey J. TI ERK activation of p21 activated kinase-1 (Pak1) is critical for medulloblastoma cell migration SO CLINICAL & EXPERIMENTAL METASTASIS LA English DT Article DE ERK; Medullobastoma; Migration; Pak1; PDGF ID ACTIN STRESS FIBERS; BREAST-CANCER CELLS; MALIGNANT BRAIN-TUMORS; RHO GTPASES; SIGNALING PATHWAYS; FOCAL COMPLEXES; IN-VIVO; EXPRESSION; KINASE; RAC AB We previously identified that overexpression of the platelet-derived growth factor receptor (PDGFR) is associated with metastatic medulloblastoma (MB) and showed that PDGF treatment increases ERK activity and promotes MB cell migration. In this study, we investigated whether ERK regulates Rac1/Pak1 signaling and is critically linked to MB cell migration. Herein we demonstrate that PDGF-BB treatment of MB cells induces concomitant activation of PDGFR beta, MEK1/ERK, Rac1 and Pak1, but suppresses Rho activity, which together significantly promotes cell migration. Conversely, cells transfected with either PDGFR beta or Pak1 siRNA or treated with an inhibitor of Rac1 (NSC23766) or N-myristoyltransferase-1 (Tris-dipalladium) are unable to activate Rac1 or Pak1 in response to PDGF, and consequently, are unable to undergo PDGF-mediated cell migration. Furthermore, we also demonstrate that either chemical inhibition of MEK/ERK (U0126) or stable downregulation of PDGFR beta by shRNA similarly results in the loss of PDGF-induced ERK phosphorylation and abolishes Rac1/Pak1 activation and cell migration in response to PDGF. However, specific depletion of Pak1 by siRNA has no effect on PDGF-induced ERK phosphorylation, indicating that in MB cells ERK signaling is Pak1-independent, but PDGF-induced migration is dependent on ERK-mediated activation of Pak1. Finally, using tissue microarrays, we detect phosphorylated Pak1 in 53% of medulloblastomas and show that immunopositivity is associated with unfavorable outcome. We conclude that Rac1/Pak1 signaling is critical to MB cell migration and is functionally dependent on PDGFR beta/ERK activity. C1 [Yuan, Liangping; MacDonald, Tobey J.] Emory Univ, Sch Med, Aflac Ctr Canc & Blood Disorders, Emory Childrens Ctr, Atlanta, GA 30322 USA. [Santi, Mariarita] Childrens Hosp Philadelphia, Dept Pathol, Philadelphia, PA 19104 USA. [Rushing, Elisabeth J.] Armed Forces Inst Pathol, Dept Neuropathol, Washington, DC 20306 USA. [Cornelison, Robert] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. RP MacDonald, TJ (reprint author), Emory Univ, Sch Med, Aflac Ctr Canc & Blood Disorders, Emory Childrens Ctr, 2015 Uppergate Dr NE,Room 442, Atlanta, GA 30322 USA. EM tobey.macdonald@emory.edu RI MacDonald, Tobey/D-4554-2013 FU NIH [CA111835] FX Liangping Yuan, Mariarita Santi and Tobey J. MacDonald are supported by NIH R01 grant CA111835. NR 58 TC 21 Z9 21 U1 0 U2 5 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0262-0898 J9 CLIN EXP METASTAS JI Clin. Exp. Metastasis PD OCT PY 2010 VL 27 IS 7 BP 481 EP 491 DI 10.1007/s10585-010-9337-9 PG 11 WC Oncology SC Oncology GA 654NX UT WOS:000282176300003 PM 20526801 ER PT J AU Seeff, LB Everson, GT Morgan, TR Curto, TM Lee, WM Ghany, MG Shiffman, ML Fontana, RJ Di Bisceglie, AM Bonkovsky, HL Dienstag, JL AF Seeff, Leonard B. Everson, Gregory T. Morgan, Timothy R. Curto, Teresa M. Lee, William M. Ghany, Marc G. Shiffman, Mitchell L. Fontana, Robert J. Di Bisceglie, Adrian M. Bonkovsky, Herbert L. Dienstag, Jules L. CA HALT-C Trial Grp TI Complication Rate of Percutaneous Liver Biopsies Among Persons With Advanced Chronic Liver Disease in the HALT-C Trial SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article DE Liver Biopsy; Complications; Adverse Event; Serious Adverse Events; Bleeding; Platelet Count; INR ID CHRONIC HEPATITIS-C; COAGULATION; RISK; INTERFERON; THERAPY; AUDIT; MODEL AB BACKGROUND & AIMS: Although percutaneous liver biopsy is a standard diagnostic procedure, it has drawbacks, including risk of serious complications. It is not known whether persons with advanced chronic liver disease have a greater risk of complications from liver biopsy than patients with more mild, chronic liver disease. The safety and complications of liver biopsy were examined in patients with hepatitis C-related bridging fibrosis or cirrhosis who were enrolled in the Hepatitis C Antiviral Long-Term Treatment against Cirrhosis trial. METHODS: Standard case report forms from 2740 liver biopsies performed at 10 study sites between 2000 and 2006 were reviewed for serious adverse events, together with information from questionnaires completed by investigators about details of biopsy techniques used at each hospital. RESULTS: There were 29 serious adverse events (1.1%); the most common was bleeding (16 cases; 0.6%). There were no biopsy-related deaths. The bleeding rare was higher among patients with platelet counts of 60,000/mm(3) or less and among those with an international normalized ratio of 1.3 or greater, although none of the patients with an international normalized ratio greater than 1.5 bled. Excluding subjects with a platelet count of 60,000/mm(3) or less would have reduced the bleeding rate by 25% (4 of 16), eliminating only 2.8% (77 of 2740) of biopsies. Operator experience, the type of needle used, or the performance of the biopsy under ultrasound guidance did not influence the frequencies of adverse events. CONCLUSIONS: Approximately 0.5% of persons with hepatitis C and advanced fibrosis experienced potentially serious bleeding after liver biopsy; risk increased significantly in patients with platelet counts of 60,000/mm(3) or less. C1 [Seeff, Leonard B.] NIDDK, Div Digest Dis & Nutr, NIH, US Dept HHS, Bethesda, MD 20892 USA. [Ghany, Marc G.] NIDDK, Liver Dis Branch, NIH, US Dept HHS, Bethesda, MD 20892 USA. [Everson, Gregory T.] Univ Colorado Denver, Sch Med, Div Gastroenterol & Hepatol, Sect Hepatol, Aurora, CO USA. [Morgan, Timothy R.] Univ Calif Irvine, Div Gastroenterol, Irvine, CA USA. [Morgan, Timothy R.] VA Long Beach Healthcare Syst, Gastroenterol Serv, Long Beach, CA USA. [Curto, Teresa M.] New England Res Inst, Watertown, MA 02172 USA. [Lee, William M.] Univ Texas SW Med Ctr Dallas, Div Digest & Liver Dis, Dallas, TX 75390 USA. [Shiffman, Mitchell L.] Bon Secours Hlth Syst, Liver Inst Virginia, Newport News, VA USA. [Shiffman, Mitchell L.] Bon Secours Hlth Syst, Liver Inst Virginia, Richmond, VA USA. [Fontana, Robert J.] Univ Michigan, Sch Med, Dept Internal Med, Div Gastroenterol, Ann Arbor, MI USA. [Di Bisceglie, Adrian M.] St Louis Univ, Sch Med, Div Gastroenterol & Hepatol, St Louis, MO USA. [Bonkovsky, Herbert L.] Univ Connecticut, Ctr Hlth, Dept Med, Farmington, CT USA. [Bonkovsky, Herbert L.] Univ Connecticut, Ctr Hlth, Dept Mol & Struct Biol, Farmington, CT USA. [Bonkovsky, Herbert L.] Univ Connecticut, Ctr Hlth, Liver Biliary Pancreat Ctr, Farmington, CT USA. [Dienstag, Jules L.] Harvard Univ, Massachusetts Gen Hosp, Med Serv, Gastrointestinal Unit, Boston, MA 02115 USA. [Dienstag, Jules L.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Seeff, LB (reprint author), NIDDK, Div Digest Dis & Nutr, NIH, US Dept HHS, 31A Ctr Dr,Room 9A27, Bethesda, MD 20892 USA. EM seeffl@extra.niddk.nih.gov FU National Institute of Diabetes & Digestive & Kidney Diseases; Hoffmann-La Roche, Inc FX This study was supported by the National Institute of Diabetes & Digestive & Kidney Diseases (contract numbers are listed above). Additional support was provided by the National Institute of Allergy and Infectious Diseases, the National Cancer Institute, the National Center for Minority Health and Health Disparities, and by General Clinical Research Center and Clinical and Translational Science Center grants from the National Center for Research Resources, National Institutes of Health (grant numbers are listed above). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health. Additional funding to conduct this study was supplied by Hoffmann-La Roche, Inc, through a Cooperative Research and Development Agreement with the National Institutes of Health. NR 31 TC 96 Z9 100 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD OCT PY 2010 VL 8 IS 10 BP 877 EP 883 DI 10.1016/j.cgh.2010.03.025 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 665NM UT WOS:000283042500014 PM 20362695 ER PT J AU Izumi, K Culler, D Solomon, BD Muenke, M Parikh, AS AF Izumi, K. Culler, D. Solomon, B. D. Muenke, M. Parikh, A. S. TI Submicroscopic familial chromosomal translocation between 7q and 12p mimicking an autosomal dominant holoprosencephaly syndrome SO CLINICAL GENETICS LA English DT Letter ID SONIC HEDGEHOG GENE C1 [Izumi, K.; Culler, D.; Parikh, A. S.] Univ Hosp Case Med Ctr, Ctr Human Genet, Cleveland, OH 44106 USA. [Izumi, K.; Culler, D.; Parikh, A. S.] Case Western Reserve Univ, Dept Genet, Cleveland, OH 44106 USA. [Izumi, K.; Parikh, A. S.] Rainbow Babies & Childrens Hosp, Dept Pediat, Cleveland, OH 44106 USA. [Solomon, B. D.; Muenke, M.] NHGRI, NIH, Med Genet Branch, Bethesda, MD 20892 USA. RP Izumi, K (reprint author), Univ Hosp Case Med Ctr, Ctr Human Genet, Cleveland, OH 44106 USA. EM Kosuke.Izumi@UHhospitals.org FU Intramural NIH HHS [ZIA HG000209-10] NR 6 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0009-9163 J9 CLIN GENET JI Clin. Genet. PD OCT PY 2010 VL 78 IS 4 BP 402 EP 404 DI 10.1111/j.1399-0004.2010.01437.x PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 647TE UT WOS:000281641300016 PM 20412079 ER PT J AU Semba, RD Patel, KV Ferrucci, L Sun, K Roy, CN Guralnik, JM Fried, LP AF Semba, Richard D. Patel, Kushang V. Ferrucci, Luigi Sun, Kai Roy, Cindy N. Guralnik, Jack M. Fried, Linda P. TI Serum antioxidants and inflammation predict red cell distribution width in older women: The Women's Health and Aging Study I SO CLINICAL NUTRITION LA English DT Article DE Carotenoids; Interleukin-6; Oxidative stress; Red cell distribution width; Selenium; Vitamin E ID GLUTATHIONE-PEROXIDASE; OXIDATIVE STRESS; BLOOD COMPONENTS; BOWEL-DISEASE; BETA-CAROTENE; SELENIUM; SUPPLEMENTATION; DAMAGE; MORTALITY; BIOMARKERS AB Background & aims: Red cell distribution width (ROW), a measure of heterogeneity in the size of circulating erythrocytes, is associated with some chronic diseases and predicts mortality. Although oxidative damage and inflammation have been theorized to affect ROW, the relationships of antioxidants and inflammation with RDW have not been well characterized. The aims were to determine whether total serum carotenoids, alpha-tocopherol, selenium, protein carbonyls, and interleukin-6 (IL-6) are associated with ROW and predict RDW over time. Methods: ROW was measured at baseline, 12 months, and 24 months follow-up in 786 moderately to severely disabled community-dwelling women, aged >= 65 years, in the Women's Health and Aging Study I in Baltimore, Maryland. Results: Selenium was significantly associated with RDW at baseline and predicted RDW over two years' follow-up in separate multivariate mixed-effects models that adjusted for other covariates. As expected, the addition of IL-6 to the models attenuated the association of serum selenium with ROW, as low antioxidant levels are known to upregulate IL-6. Total carotenoids were associated with RDW at baseline and one year follow-up. Protein carbonyls and a-tocopherol were not significantly associated with ROW. Conclusion: Serum selenium is an independent predictor of ROW and may potentially mediate effects on RDW through IL-6. (C) 2010 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved. C1 [Semba, Richard D.; Sun, Kai; Roy, Cindy N.; Fried, Linda P.] Johns Hopkins Univ, Sch Med, Baltimore, MD 21287 USA. [Patel, Kushang V.; Guralnik, Jack M.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Ferrucci, Luigi] NIA, Clin Res Branch, Bethesda, MD 20892 USA. RP Semba, RD (reprint author), Johns Hopkins Univ, Sch Med, 400 N Broadway,Room M015, Baltimore, MD 21287 USA. EM rdsemba@jhmi.edu FU National Institute on Aging [R01 AG027012, R01 AG029148]; National Institute on Aging, National Institutes of Health FX This work was supported by National Institute on Aging Grants R01 AG027012, R01 AG029148 and the Intramural Research Program, National Institute on Aging, National Institutes of Health. The funding agency had no role in the conduct of the study or the data analysis. The study hypothesis and design were conceived by RDS, KVP, LF, and JMG. Funding was obtained by RDS, LF, and LPF. The data analysis was conducted by KS. The manuscript was written by RDS with substantial contributions to the paper by KVP, LF, KS, CNR, JMG, and LPF. All authors contributed to the final manuscript. NR 32 TC 94 Z9 97 U1 0 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0261-5614 J9 CLIN NUTR JI Clin. Nutr. PD OCT PY 2010 VL 29 IS 5 BP 600 EP 604 DI 10.1016/j.clnu.2010.03.001 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 673BE UT WOS:000283632400009 PM 20334961 ER PT J AU Maggio, M Ceda, GP Lauretani, F Bandinelli, S Dall'Aglio, E Guralnik, JM Paolisso, G Semba, RD Nouvenne, A Borghi, L Ceresini, G Ablondi, F Benatti, M Ferrucci, L AF Maggio, Marcello Ceda, Gian Paolo Lauretani, Fulvio Bandinelli, Stefania Dall'Aglio, Elisabetta Guralnik, Jack M. Paolisso, Giuseppe Semba, Richard D. Nouvenne, Antonio Borghi, Loris Ceresini, Graziano Ablondi, Fabrizio Benatti, Mario Ferrucci, Luigi TI Association of plasma selenium concentrations with total IGF-1 among older community-dwelling adults: The InCHIANTI study SO CLINICAL NUTRITION LA English DT Article DE Aging; Total IGF-1; Selenium ID GROWTH-FACTOR-I; MUSCLE STRENGTH; INFLAMMATION; WOMEN AB Background & aims: Insulin-like growth factor (IGF-1) stimulates cell proliferation and inhibits cell apoptosis. Recent studies underline its importance as anabolic hormone and nutritional marker in older individuals. IGF-1 synthesis and bioactivity are modulated by nutritional factors including selenium intake. However, whether circulating IGF-1 levels are positively influenced by plasma selenium, one of the most important human antioxidants, is still unknown. Methods: Selenium and total IGF-1 were measured in 951 men and women >= 65 years from the InCHIANTI study, Tuscany, Italy. Results: Means (SD) of plasma selenium and total IGF-1 were 0.95 (0.15) mu mol/L and 113.4 (31.2) ng/mL, respectively. After adjustment for age and sex, selenium levels were positively associated with total IGF-1 (13 SE: 43.76 +/- 11.2, p = 0.0001). After further adjustment for total energy and alcohol intake, serum alanine aminotransferase (ALT), congestive heart failure, selenium remained significantly associated with IGF-1 (beta +/- SE: 36.7 +/- 12.2, p = 0.003). The association was still significant when IL-6 was introduced in the model (beta +/- SE: 40.1 +/- 12.0, p = 0.0008). Conclusions: We found an independent, positive and significant association between selenium and IGF-1 serum levels in community dwelling older adults. (C) 2010 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved. C1 [Maggio, Marcello; Ceda, Gian Paolo; Dall'Aglio, Elisabetta; Ceresini, Graziano; Ablondi, Fabrizio] Univ Parma, Dept Internal Med & Biomed Sci, Sect Geriatr, I-43100 Parma, Italy. [Maggio, Marcello; Ceda, Gian Paolo; Lauretani, Fulvio; Ceresini, Graziano] Univ Hosp Parma, Geriatr Rehabil Dept, Parma, Italy. [Bandinelli, Stefania] Geriatr Unit, Florence, Italy. [Guralnik, Jack M.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Paolisso, Giuseppe] Univ Naples 2, VI Unit Internal Med, Dept Geriatr Med & Metab Dis, Naples, Italy. [Semba, Richard D.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Nouvenne, Antonio; Borghi, Loris] Univ Parma, Dept Clin Sci, I-43100 Parma, Italy. [Ferrucci, Luigi] NIA, Natl Inst Hlth, Intramural Res Program, Longitudinal Studies Sect,Clin Res Branch, Baltimore, MD 21224 USA. RP Maggio, M (reprint author), Univ Parma, Dept Internal Med & Biomed Sci, Sect Geriatr, Via Gramsci 14, I-43100 Parma, Italy. EM marcellomaggio2001@yahoo.it RI Lauretani, Fulvio/K-5115-2016; OI Paolisso, Giuseppe/0000-0002-2137-455X; Lauretani, Fulvio/0000-0002-5287-9972; Ceda, Gian Paolo/0000-0002-9648-8295; Nouvenne, Antonio/0000-0002-2680-2242 FU National Institute on Aging [N01-AG-916413, N01-AG-821336, N01-AG-5-0002]; NIA [R01 AG027012]; National Institute on Aging, NIH FX This work was supported by National Institute on Aging Contracts N01-AG-916413, N01-AG-821336, N01-AG-5-0002, and NIA Grant R01 AG027012. This research was supported in part by the Intramural Research Program, National Institute on Aging, NIH. NR 14 TC 13 Z9 13 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0261-5614 J9 CLIN NUTR JI Clin. Nutr. PD OCT PY 2010 VL 29 IS 5 BP 674 EP 677 DI 10.1016/j.clnu.2010.03.012 PG 4 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 673BE UT WOS:000283632400020 PM 20416996 ER PT J AU Nelson, SJ Schulman, JL AF Nelson, Stuart J. Schulman, Jacque-Lynne TI Orthopaedic Literature and MeSH SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article AB Since 1916 there has been a recognized demand for a method of classification of orthopaedic literature inclusive enough to permit the proper collection and retrieval of all literature on the subject. Today, MEDLINE, available through the PubMed interface, has become the de facto standard for organization and retrieval of medical literature. The Medical Subject Headings (MeSH), used to provide indexing and assist in searching, are partly responsible for this standard. Understanding how MeSH is built and maintained may lead the user to a better understanding of how to use MEDLINE, and what to expect from the indexing of an article. The purpose of this review is to provide an understanding of the organization of large quantities of indexed material, the indexing process and the considerations involved in developing an indexing vocabulary. Successful terminology development and use, a prerequisite for any sharing of information by electronic means, depends on both user (how the user is expected to use the system) and information (how the information is organized) models. MEDLINE has a simple user model and a simpler information model. The user is expected to determine what is relevant and which MeSH descriptors are appropriate. While MEDLINE through PubMed is a success as viewed by the number of hits, further improvements will depend on better, faster indexing with a controlled terminology. Terminology development requires careful consideration of the nature of the subject, how users employ the terminology, the overall purpose of the terminology, and the framework of the systems in which it is used. For the future, understanding terminology development might enable the user to comprehend some of the issues involved in sharing of other information by electronic means. Further improvements in the availability and accessibility of medical literature will depend on continued maintenance and development of MeSH, as well as on refinement of the indexing process. C1 [Nelson, Stuart J.; Schulman, Jacque-Lynne] Natl Lib Med, Lib Operat, Bethesda, MD 20894 USA. RP Nelson, SJ (reprint author), Natl Lib Med, Lib Operat, 8600 Rockville Pike,Room B2E17, Bethesda, MD 20894 USA. EM nelsonst@mail.nih.gov NR 13 TC 5 Z9 5 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD OCT PY 2010 VL 468 IS 10 BP 2621 EP 2626 DI 10.1007/s11999-010-1387-4 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 650IT UT WOS:000281843200010 PM 20623263 ER PT J AU Mattson, MP Kapogiannis, D Greig, NH AF Mattson, M. P. Kapogiannis, D. Greig, N. H. TI Tweaking Energy Metabolism to Prevent and Treat Neurological Disorders SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Editorial Material C1 [Mattson, M. P.; Greig, N. H.] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. [Kapogiannis, D.] NIA, Clin Res Branch, 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 FU Intramural NIH HHS [Z99 AG999999, ZIA AG000975-03] NR 0 TC 5 Z9 5 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD OCT PY 2010 VL 88 IS 4 BP 437 EP 439 DI 10.1038/clpt.2010.135 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 653CR UT WOS:000282064000007 PM 20856237 ER PT J AU Simon, R AF Simon, Richard TI Clinical trials for predictive medicine: new challenges and paradigms SO CLINICAL TRIALS LA English DT Article; Proceedings Paper CT Annual Conference on Statistical Issues on Clinical Trials - Statistical Issues in Developing Targeted Therapies CY APR 29, 2009 CL Univ Pennsylvania, Philadelphia, PA SP Amer Stat Assoc, Soc Clinical Trials HO Univ Pennsylvania ID REQUIRING PROLONGED OBSERVATION; ADAPTIVE SIGNATURE DESIGN; GENE-EXPRESSION SIGNATURE; BREAST-CANCER; SUBSET; EFFICIENCY; PATIENT AB Background Developments in biotechnology and genomics have increased the focus of biostatisticians on prediction problems. This has led to many exciting developments for predictive modeling where the number of variables is larger than the number of cases. Heterogeneity of human diseases and new technology for characterizing them presents new opportunities and challenges for the design and analysis of clinical trials. Purpose In oncology, treatment of broad populations with regimens that do not benefit most patients is less economically sustainable with expensive molecularly targeted therapeutics. The established molecular heterogeneity of human diseases requires the development of new paradigms for the design and analysis of randomized clinical trials as a reliable basis for predictive medicine [Simon R. An agenda for clinical trials: clinical trials in the genomic era. Clin Trials 2004; 1: 468-70, Simon R. New challenges for 21st century clinical trials. Clin Trials 2007; 4: 167-9.]. Results We have reviewed prospective designs for the development of new therapeutics with candidate predictive biomarkers. We have also outlined a prediction based approach to the analysis of randomized clinical trials that both preserves the type I error and provides a reliable internally validated basis for predicting which patients are most likely or unlikely to benefit from the new regimen. Conclusions Developing new treatments with predictive biomarkers for identifying the patients who are most likely or least likely to benefit makes drug development more complex. But for many new oncology drugs it is the only science based approach and should increase the chance of success. It may also lead to more consistency in results among trials and has obvious benefits for reducing the number of patients who ultimately receive expensive drugs which expose them risks of adverse events but no benefit. This approach also has great potential value for controlling societal expenditures on health care. Development of treatments with predictive biomarkers requires major changes in the standard paradigms for the design and analysis of clinical trials. Some of the key assumptions upon which current methods are based are no longer valid. In addition to reviewing a variety of new clinical trial designs for co-development of treatments and predictive biomarkers, we have outlined a prediction based approach to the analysis of randomized clinical trials. This is a very structured approach whose use requires careful prospective planning. It requires further development but may serve as a basis for a new generation of predictive clinical trials which provide the kinds of reliable individualized information which physicians and patients have long sought, but which have not been available from the past use of post-hoc subset analysis. Clinical Trials 2010; 7: 516-524. http://ctj.sagepub.com C1 NCI, Biometr Res Branch, Bethesda, MD 20892 USA. RP Simon, R (reprint author), NCI, Biometr Res Branch, 9000 Rockville Pike,MSC7434, Bethesda, MD 20892 USA. EM rsimon@nih.gov FU NCI NIH HHS [R13 CA132565] NR 23 TC 37 Z9 38 U1 1 U2 2 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1740-7745 J9 CLIN TRIALS JI Clin. Trials PD OCT PY 2010 VL 7 IS 5 BP 516 EP 524 DI 10.1177/1740774510366454 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 653KK UT WOS:000282089800002 PM 20338899 ER PT J AU Liu, AY Liu, CL Li, QZ Yu, KF Yuan, VW AF Liu, Aiyi Liu, Chunling Li, Qizhai Yu, Kai F. Yuan, Vivian W. TI A threshold sample-enrichment approach in a clinical trial with heterogeneous subpopulations SO CLINICAL TRIALS LA English DT Article; Proceedings Paper CT Annual Conference on Statistical Issues on Clinical Trials - Statistical Issues in Developing Targeted Therapies CY APR 29, 2009 CL Univ Pennsylvania, Philadelphia, PA SP Amer Stat Assoc, Soc Clinical Trials HO Univ Pennsylvania ID PREECLAMPSIA; PREVENTION; SUBGROUP; CALCIUM AB Background Large comparative clinical trials usually target a wide-range of patients population in which subgroups exist according to certain patients' characteristics. Often, scientific knowledge or existing empirical data support the assumption that patients' improvement is larger among certain subgroups than others. Such information can be used to design a more cost-effective clinical trial. Purpose The goal of the article is to use such information to design a more cost-effective clinical trial. Methods A two-stage sample-enrichment design strategy is proposed that begins with enrollment from certain subgroup of patients and allows the trial to be terminated for futility in that subgroup. Results Simulation studies show that the two-stage sample-enrichment strategy is cost-effective if indeed the null hypothesis of no treatment improvement is true, as also so illustrated with data from a completed trial of calcium to prevent preeclampsia. Limitations Feasibility of the proposed enrichment design relies on the knowledge prior to the start of the trial that certain patients can benefit more than others from the treatment. Prolonged accrual and longer-waited outcomes may hinder utilization of the proposed design. Conclusions The two-stage sample-enrichment approach borrows strength from treatment heterogeneity among target patients in a large-scale comparative clinical trial, and is more cost-effective if the treatment arms are indeed of no difference. Clinical Trials 2010; 7: 537-545. http://ctj.sagepub.com C1 [Liu, Aiyi; Liu, Chunling; Yu, Kai F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Rockville, MD 20852 USA. [Li, Qizhai] Chinese Acad Sci, Acad Math & Syst Sci, Beijing, Peoples R China. [Yuan, Vivian W.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Liu, AY (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Rockville, MD 20852 USA. EM liua@mail.nih.gov RI Liu, Chunling/A-4827-2015; OI Liu, Chunling/0000-0003-3410-445X; Liu, Aiyi/0000-0002-6618-5082 FU Intramural NIH HHS [Z99 HD999999] NR 9 TC 14 Z9 14 U1 0 U2 2 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1740-7745 J9 CLIN TRIALS JI Clin. Trials PD OCT PY 2010 VL 7 IS 5 BP 537 EP 545 DI 10.1177/1740774510378695 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 653KK UT WOS:000282089800004 PM 20685769 ER PT J AU Joo, J Geller, NL French, B Kimmel, SE Rosenberg, Y Ellenberg, JH AF Joo, Jungnam Geller, Nancy L. French, Benjamin Kimmel, Stephen E. Rosenberg, Yves Ellenberg, Jonas H. TI Prospective alpha allocation in the clarification of optimal anticoagulation through genetics (COAG) trial SO CLINICAL TRIALS LA English DT Article; Proceedings Paper CT Annual Conference on Statistical Issues on Clinical Trials - Statistical Issues in Developing Targeted Therapies CY APR 29, 2009 CL Univ Pennsylvania, Philadelphia, PA SP Amer Stat Assoc, Soc Clinical Trials HO Univ Pennsylvania ID CLINICAL-TRIALS; WARFARIN; THERAPY; CYP2C9; OUTCOMES AB Background The Clarification of Optimal Anticoagulation through Genetics (COAG) trial is a large, multicenter, double-blinded, randomized trial to determine whether use of a genotype-guided dosing algorithm (using clinical and genetic information) to initiate warfarin treatment will improve anticoagulation status when compared to a dosing algorithm using only clinical information. Purpose This article describes prospective alpha allocation and balanced alpha allocation for the design of the COAG trial. Methods The trial involves two possibly heterogeneous populations, which can be distinguished by the difference in warfarin dose as predicted by the two algorithms. A statistical approach is detailed, which allows an overall comparison as well as a comparison of the primary endpoint in the subgroup for which sufficiently different doses are predicted by the two algorithms. Methods of allocating alpha for these analyses are given - a prospective alpha allocation and allocating alpha so that the two analyses have equal power, which we call a 'balanced alpha allocation.' Results We show how to include an analysis of the primary endpoint in a subgroup as a co-primary analysis. Power can be improved by incorporating the correlation between the overall and subgroup analyses in a prospective alpha allocation approach. Balanced alpha allocation for the full cohort and subgroup tests to achieve the same desired power for both of the primary analyses is discussed in detail. Limitations In the COAG trial, it is impractical to stratify the randomization on subgroup membership because genetic information may not be available at the time of randomization. If imbalances in the treatment arms in the subgroup are found, they will need to be addressed. Conclusions The design of the COAG trial assures that the subgroup in which the largest treatment difference is expected is elevated to a co-primary analysis. Incorporating the correlation between the full cohort and the subgroup analyses provides an improvement in power for the subgroup comparison, and further improvement may be achieved via a balanced alpha allocation approach when the parameters involved in the sample size calculation are reasonably well estimated. Clinical Trials 2010; 7: 597-604. http://ctj.sagepub.com C1 [Joo, Jungnam; Geller, Nancy L.] NHLBI, Off Biostat Res, NIH, Bethesda, MD 20892 USA. [French, Benjamin; Kimmel, Stephen E.; Ellenberg, Jonas H.] Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Rosenberg, Yves] NHLBI, Atherothrombosis & Coronary Artery Dis Branch, Bethesda, MD 20892 USA. RP Joo, J (reprint author), NHLBI, Off Biostat Res, NIH, 6701 Rockledge Dr,MSC 7913, Bethesda, MD 20892 USA. EM jooj@nhlbi.nih.gov FU None [HHSN268200800003C]; PHS HHS [HHSN268200800003C] NR 24 TC 16 Z9 17 U1 0 U2 1 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1740-7745 J9 CLIN TRIALS JI Clin. Trials PD OCT PY 2010 VL 7 IS 5 BP 597 EP 604 DI 10.1177/1740774510381285 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 653KK UT WOS:000282089800010 PM 20693186 ER PT J AU Ellenberg, JH Wang, SJ Geller, N Liu, AY Ellenberg, S Zhou, A Simon, R AF Ellenberg, Jonas H. Wang, Sue-Jane Geller, Nancy Liu, Aiyi Ellenberg, Susan Zhou, Andrew Simon, Richard TI Prospective alpha allocation in the clarification of optimal anticoagulation through genetics (COAG) trial Floor Discussion I SO CLINICAL TRIALS LA English DT Editorial Material ID CLINICAL-TRIALS C1 [Ellenberg, Jonas H.; Ellenberg, Susan] Univ Penn, Philadelphia, PA 19104 USA. [Geller, Nancy] NHLBI, Bethesda, MD 20892 USA. [Simon, Richard] NCI, Bethesda, MD 20892 USA. RP Ellenberg, JH (reprint author), Univ Penn, Philadelphia, PA 19104 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1740-7745 J9 CLIN TRIALS JI Clin. Trials PD OCT PY 2010 VL 7 IS 5 BP 605 EP 607 DI 10.1177/1740774510380505 PG 3 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 653KK UT WOS:000282089800011 ER PT J AU Mietlowski, B Sargent, D Chen, A Lee, JJ Zhou, A Li, DG Kim, SS Simon, R Day, R AF Mietlowski, Bill Sargent, Dan Chen, Adam Lee, J. Jack Zhou, Andrew Li, Dongguang Kim, Sun Soo Simon, Richard Day, Roger TI Prospective alpha allocation in the clarification of optimal anticoagulation through genetics (COAG) trial Floor Discussion II SO CLINICAL TRIALS LA English DT Editorial Material C1 [Chen, Adam] Eli Lilly & Co, Indianapolis, IN USA. [Zhou, Andrew] Univ Washington, Seattle, WA 98195 USA. [Simon, Richard] NCI, Bethesda, MD 20892 USA. [Day, Roger] Univ Pittsburgh, Pittsburgh, PA 15260 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1740-7745 J9 CLIN TRIALS JI Clin. Trials PD OCT PY 2010 VL 7 IS 5 BP 608 EP 610 DI 10.1177/1740774510380507 PG 3 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 653KK UT WOS:000282089800012 ER PT J AU Ellenberg, S Ruberg, S Simon, R Wang, SJ Xu, LA Anderson, K AF Ellenberg, Susan Ruberg, Stephen Simon, Richard Wang, Sue-Jane Xu, Li-an Anderson, Keaven TI Prospective alpha allocation in the clarification of optimal anticoagulation through genetics (COAG) trial Closing discussion SO CLINICAL TRIALS LA English DT Editorial Material C1 [Ellenberg, Susan] Univ Penn, Philadelphia, PA 19104 USA. [Ruberg, Stephen] Eli Lilly & Co, Indianapolis, IN USA. [Simon, Richard] NCI, Bethesda, MD 20892 USA. [Wang, Sue-Jane] US FDA, Rockville, MD 20857 USA. [Xu, Li-an] Bristol Myers Squibb Co, New York, NY 10154 USA. RP Ellenberg, S (reprint author), Univ Penn, Philadelphia, PA 19104 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1740-7745 J9 CLIN TRIALS JI Clin. Trials PD OCT PY 2010 VL 7 IS 5 BP 611 EP 616 DI 10.1177/1740774510380503 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 653KK UT WOS:000282089800013 ER PT J AU Brining, DL Mattoon, JS Kercher, L LaCasse, RA Safronetz, D Feldmann, H Parnell, MJ AF Brining, Douglas L. Mattoon, John S. Kercher, Lisa LaCasse, Rachael A. Safronetz, David Feldmann, Heinz Parnell, Michael J. TI Thoracic Radiography as a Refinement Methodology for the Study of H1N1 Influenza in Cynomologus Macaques (Macaca fascicularis) SO COMPARATIVE MEDICINE LA English DT Article ID CT FINDINGS; INFECTION; VACCINES; VIRUS AB Recent advances in the technology associated with digital radiography have created new opportunities for biomedical research applications. Here we evaluated the use of thoracic radiography as a noninvasive refinement methodology for the cynomologus macaque (Macaca fascicularis) model of H1N1 infection. Thoracic radiographic evaluations of macaques infected with any of 3 strains of emerging H1N1 swine-associated influenza virus isolated during the recent pandemic were compared with those of macaques infected with the currently circulating Kawasaki strain of H1N1 influenza. Ventrodorsal, right, and left lateral thoracic radiographs were obtained at days 0, 1, 6, 8, 11, and 14 after infection. A board-certified veterinary radiologist who was blinded to the study design evaluated the images. Numeric scores of extent and severity of lung involvement assigned to each radiograph were compared and demonstrated a significant and substantial difference among groups. The radiographic evaluation allowed for noninvasive assessment of lung involvement, disease onset, progression, and resolution of radiographic changes associated with H1N1 influenza infection. C1 [Brining, Douglas L.; Kercher, Lisa; LaCasse, Rachael A.; Parnell, Michael J.] NIAID, Rocky Mt Vet Branch, NIH, Hamilton, MT USA. [Safronetz, David; Feldmann, Heinz] NIAID, Virol Lab, Rocky Mt Labs, Div Intramural Res,Natl Inst Hlth, Hamilton, MT USA. [Mattoon, John S.] Washington State Univ, Dept Vet Clin Sci, Pullman, WA 99164 USA. RP Brining, DL (reprint author), NIAID, Rocky Mt Vet Branch, NIH, Hamilton, MT USA. FU Division of Intramural Research of National Institute of Allergy and Infectious Diseases, NIH FX This research was supported by the Division of Intramural Research of National Institute of Allergy and Infectious Diseases, NIH We thank Barry Rockx, Friederike Feldmann, Don Gardner, Andrea Marzi, Hideki Ebihara, Anthony York, William Shupert, and Dan Long for their scientific contributions to the larger swine-origin H1N1 influenza pathogenesis study We also thank Edward Schreckendgust, Rocky Rivera, Sandy Skorupa, and Kathleen Meuchel for their assistance with animal care and sample collection We are thankful to Martha Nason and Anita Mora for their assistance with the statistical evaluation of the radiographic scores and preparation of the radiographic images, respectively NR 21 TC 19 Z9 19 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1532-0820 J9 COMPARATIVE MED JI Comparative Med. PD OCT PY 2010 VL 60 IS 5 BP 389 EP 395 PG 7 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 669YB UT WOS:000283385000009 PM 21262125 ER PT J AU Della Sala, S Grafman, J AF Della Sala, Sergio Grafman, Jordan TI Cortex 2009 5-year and 2-year Impact Factor: 4.1 SO CORTEX LA English DT Editorial Material C1 [Della Sala, Sergio] Univ Edinburgh, Dept Psychol, Edinburgh EH8 9JZ, Midlothian, Scotland. [Grafman, Jordan] Natl Inst Neurol Disorders & Stroke, Cognit Neurosci Sect, Bethesda, MD USA. RP Della Sala, S (reprint author), Univ Edinburgh, Dept Psychol, 7 George Sq, Edinburgh EH8 9JZ, Midlothian, Scotland. EM sergio@ed.ac.uk OI Grafman, Jordan H./0000-0001-8645-4457 NR 6 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER MASSON PI MILANO PA VIA PALEOCAPA 7, 20121 MILANO, ITALY SN 0010-9452 J9 CORTEX JI Cortex PD OCT PY 2010 VL 46 IS 9 BP 1069 EP 1069 DI 10.1016/j.cortex.2010.07.002 PG 1 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 659JA UT WOS:000282561600001 ER PT J AU Memoli, MJ AF Memoli, Matthew J. TI pH1N1 influenza A: Timing is everything SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE influenza A; pandemic; flu; influenza pathology; H1N1; 1918; swine influenza ID H1N1 INFLUENZA; PREGNANT-WOMEN; VIRUS; INFECTION C1 NIAID, Viral Pathogenesis & Evolut Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Memoli, MJ (reprint author), NIAID, Viral Pathogenesis & Evolut Sect, Infect Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. FU Intramural NIH HHS [Z99 AI999999] NR 18 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD OCT PY 2010 VL 38 IS 10 BP 2081 EP 2082 DI 10.1097/CCM.0b013e3181ee4061 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 652XB UT WOS:000282043800033 PM 20856004 ER PT J AU Kalil, AC Sun, JF Florescu, DF AF Kalil, Andre C. Sun, Junfeng Florescu, Diana F. TI The importance of detecting cytomegalovirus infections in studies evaluating new therapies for severe sepsis SO CRITICAL CARE MEDICINE LA English DT Article; Proceedings Paper CT Conference on Thinking Outside the Box CY MAR, 2010 CL Brussels, BELGIUM DE cytomegalovirus; sepsis; trial design; immunocompromised; survival outcome ID TUMOR-NECROSIS-FACTOR; ACTIVATED PROTEIN-C; TRANSPLANT RECIPIENTS; IMMUNOCOMPETENT MICE; REACTIVATION; STRATEGIES; EFFICACY; DISEASE; SAFETY AB Cytomegalovirus infection is present in the majority of the population and is associated with substantial morbidity and mortality in immunocompromised patients. Recently, this viral infection has also been reported in nonimmunocompromised critically ill patients. We hypothesize that active cytomegalovirus infection may confound survival outcomes in severe sepsis trials. Scenarios based on three published studies on activated protein C were used as real examples for statistical simulations looking for how much bias in favor of or against activated protein C would be observed in single-arm studies (scenario 1), phase II trials (scenario 2A/2B), and phase III trials (scenario 3A/3B). Scenario 1 simulations evaluated a single-arm study and demonstrated that confounding biases could cause an absolute decrease of 5.7% to an increase of 6.1% on mortality rates of similar studies. Scenarios 2A and 3A evaluated phase II and III trials assuming that activated protein C is truly effective; they showed that trials with an imbalance on the proportion of active cytomegalovirus infection between study arms could lead to false-negative rates (beta errors) in up to 25% of phase II trials and up to 42% of phase III trials. Scenarios 2B and 3B assumed that activated protein C was truly ineffective; they showed that imbalanced cytomegalovirus infection between arms would cause false-positive rates (beta errors) in up to 5% of phase II and up to 7% of all phase III trials. The inclusion of an imbalanced proportion of patients with active cytomegalovirus infection may severely compromise the reliability of outcome results of severe sepsis trials independent of their design. Even randomized trials could have a much higher probability of false-negative rates for a new therapy than designed. Future severe sepsis trials should consider including active cytomegalovirus infection as a prospective covariate. (Crit Care Med 2010; 38[Suppl.]:S663-S667) C1 [Kalil, Andre C.; Florescu, Diana F.] Univ Nebraska Med Ctr, Dept Med, Omaha, NE USA. [Sun, Junfeng] NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. RP Kalil, AC (reprint author), Univ Nebraska Med Ctr, Dept Med, Omaha, NE USA. EM akalil@unmc.edu NR 14 TC 5 Z9 6 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD OCT PY 2010 VL 38 SU S BP S663 EP S667 DI 10.1097/CCM.0b013e3181f20319 PG 5 WC Critical Care Medicine SC General & Internal Medicine GA 745EP UT WOS:000289148900024 PM 21164412 ER PT J AU Falk-Krzesinski, HJ Borner, K Contractor, N Fiore, SM Hall, KL Keyton, J Spring, B Stokols, D Trochim, W Uzzi, B AF Falk-Krzesinski, Holly J. Boerner, Katy Contractor, Noshir Fiore, Stephen M. Hall, Kara L. Keyton, Joann Spring, Bonnie Stokols, Daniel Trochim, William Uzzi, Brian TI Advancing the Science of Team Science SO CTS-CLINICAL AND TRANSLATIONAL SCIENCE LA English DT Article DE editorial; editorials; translational research ID COLLABORATION AB The First Annual International Science of Team Science (SciTS) Conference was held in Chicago, IL April 22-24, 2010. This article presents a summary of the Conference proceedings. Clin Trans Sci 2010; Volume 3: 263-266. C1 [Falk-Krzesinski, Holly J.] Northwestern Univ, Clin & Translat Sci NUCATS Inst, Res Team Support, Chicago, IL 60611 USA. [Boerner, Katy] Indiana Univ, SLIS, Cyberinfrastruct Network Sci Ctr, Bloomington, IL USA. [Contractor, Noshir] Northwestern Univ, Dept Ind Engn & Management Sci, Evanston, IL 60208 USA. [Fiore, Stephen M.] Univ Cent Florida, Dept Philosophy, Orlando, FL 32816 USA. [Fiore, Stephen M.] Univ Cent Florida, Inst Simulat & Training, Orlando, FL 32816 USA. [Hall, Kara L.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. [Keyton, Joann] N Carolina State Univ, Dept Commun, Raleigh, NC 27695 USA. [Spring, Bonnie] Northwestern Univ, Dept Prevent Med, Chicago, IL 60611 USA. [Stokols, Daniel] Univ Calif Irvine, Dept Planning Policy & Design, Irvine, CA USA. [Stokols, Daniel] Univ Calif Irvine, Dept Psychol & Social Behav, Irvine, CA USA. [Trochim, William] Cornell Univ, Dept Policy Anal & Management, Ithaca, NY USA. [Uzzi, Brian] Northwestern Univ, Dept Management & Org, Kellogg Sch Management, Evanston, IL USA. RP Falk-Krzesinski, HJ (reprint author), Northwestern Univ, Clin & Translat Sci NUCATS Inst, Res Team Support, Chicago, IL 60611 USA. EM h-falk@northwestern.edu RI Contractor, Noshir/B-7456-2009; Falk-Krzesinski, Holly/E-8870-2011; OI Falk-Krzesinski, Holly/0000-0001-8112-2445; Fiore, Stephen/0000-0003-3529-1322 FU National Institutes of Health [UL1RR025741, U24RR029822]; National Science Foundation [0915602]; Bill and Sheila Lambert; Lambert Family Communication Conference of the School of Communication at Northwestern University FX The authors comprised the Program Committee for the First Annual International SciTS Conference. The authors acknowledge fellow committee member J. Cummings of the Fuqua School of Business, Duke University, for his role in helping shape the ideas presented herein. We also wish to thank Latonia Trimuel for her role as Conference Manager and Elizabeth Kollross for editorial input on the manuscript, both at the NUCATS Institute, Northwestern University. This publication and the Conference were made possible by grant award UL1RR025741 and NIH U24RR029822 from the National Institutes of Health (NCRR CTSA and ARRA programs); by grant award 0915602 from the National Science Foundation (SES, SBE Directorate); by conference support from the NIH National Cancer Institute, Division of Cancer Control and Population Sciences; and by a philanthropic donation from Bill and Sheila Lambert, sponsors of the Lambert Family Communication Conference of the School of Communication at Northwestern University. NR 31 TC 38 Z9 38 U1 8 U2 36 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1752-8054 J9 CTS-CLIN TRANSL SCI JI CTS-Clin. Transl. Sci. PD OCT PY 2010 VL 3 IS 5 BP 263 EP 266 DI 10.1111/j.1752-8062.2010.00223.x PG 4 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 671MF UT WOS:000283509500018 PM 20973925 ER PT J AU Roschke, AV Kirsch, IR AF Roschke, Anna V. Kirsch, Ilan R. TI Targeting Karyotypic Complexity and Chromosomal Instability of Cancer Cells SO CURRENT DRUG TARGETS LA English DT Review DE Aneuploidy; chromosomal instability; cancer; anticancer drugs; NCI-60; karyotypic abnormalities; CIN; chromosomal instability phenotype ID MEROTELIC KINETOCHORE ORIENTATION; COMPARATIVE GENOMIC HYBRIDIZATION; IN-SITU HYBRIDIZATION; GENE-EXPRESSION; MAMMALIAN-CELLS; MITOTIC ARREST; MICROTUBULE DYNAMICS; COLORECTAL CANCERS; SPINDLE CHECKPOINT; ANTITUMOR-ACTIVITY AB Multiple karyotypic abnormalities and chromosomal instability are characteristic features of many cancers that are relatively resistant to chemotherapeutic agents currently used in the clinic. These same features represent potentially targetable "states" that are essentially tumor specific. The assessment of the chromosomal state of a cancer cell population may provide a guide for the selection or development of drugs active against aggressive and intractable cancers. C1 [Roschke, Anna V.; Kirsch, Ilan R.] NCI, Genet Branch, Ctr Canc Res, Bethesda, MD 20889 USA. RP Roschke, AV (reprint author), NCI, Genet Branch, Ctr Canc Res, Bldg NNMC8,Room 5101, Bethesda, MD 20889 USA. EM roschkea@mail.nih.gov FU Intramural NIH HHS [Z01 BC010930-01, Z99 CA999999] NR 99 TC 18 Z9 18 U1 1 U2 1 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1389-4501 J9 CURR DRUG TARGETS JI Curr. Drug Targets PD OCT PY 2010 VL 11 IS 10 BP 1341 EP 1350 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 692VM UT WOS:000285183900016 PM 20840077 ER PT J AU Salit, RB Bishop, MR Pavletic, SZ AF Salit, Rachel B. Bishop, Michael R. Pavletic, Steven Z. TI Allogeneic Hematopoietic Stem Cell Transplantation: Does It Have a Place in Treating Hodgkin Lymphoma? SO CURRENT HEMATOLOGIC MALIGNANCY REPORTS LA English DT Article DE Hodgkin lymphoma; Treatment; Stem cell transplantation; Reduced-intensity conditioning; Graft-versus-lymphoma effect AB Although the majority of patients with Hodgkin lymphoma achieve sustained remission with frontline treatment, there is still a subset of patients with much less favorable prognosis. The current standard of care for Hodgkin lymphoma patients with relapsed or refractory disease is autologous stem cell transplantation. However, no randomized trial has compared autologous stem cell transplantation with allogeneic stem cell transplantation prospectively, and most studies comparing allogeneic stem cell transplantation with historical controls of autologous stem cell transplantation use a myeloablative conditioning reference group. With the more frequent use of reduced-intensity conditioning transplantation in recent studies, the role for allogeneic stem cell transplantation in Hodgkin lymphoma patients is being redefined. In contrast to other types of lymphomas, Hodgkin lymphoma patients are younger at diagnosis, which makes a curative strategy such as allogeneic stem cell transplantation particularly appealing. This review examines the role of allogeneic stem cell transplantation in Hodgkin lymphoma by looking at both retrospective and prospective analyses in the era of reduced-intensity conditioning transplantation, donor lymphocyte infusions, and biologically based treatments. C1 [Salit, Rachel B.] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA. [Bishop, Michael R.; Pavletic, Steven Z.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Salit, RB (reprint author), NCI, Med Oncol Branch, NIH, Bldg 10 Hatfield CRC,Room 3-3121, Bethesda, MD 20892 USA. EM salitr@mail.nih.gov NR 43 TC 4 Z9 4 U1 1 U2 1 PU CURRENT MEDICINE GROUP PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1558-8211 J9 CURR HEMATOL MALIG R JI Curr. Hematol. Malig. Rep. PD OCT PY 2010 VL 5 IS 4 BP 229 EP 238 DI 10.1007/s11899-010-0065-7 PG 10 WC Oncology; Hematology SC Oncology; Hematology GA V25PM UT WOS:000208489900008 PM 20730513 ER PT J AU Ma, BY Nussinov, R AF Ma, Buyong Nussinov, Ruth TI Enzyme dynamics point to stepwise conformational selection in catalysis SO CURRENT OPINION IN CHEMICAL BIOLOGY LA English DT Review ID PURINE NUCLEOSIDE PHOSPHORYLASE; TRANSITION-STATE ANALOGS; DIHYDROFOLATE-REDUCTASE; ENERGY LANDSCAPE; SINGLE-MOLECULE; INDUCED-FIT; FLUCTUATING ENZYMES; ACTIVE-SITES; BINDING; DNA AB Recent data increasingly reveal that conformational dynamics are indispensable to enzyme function throughout the catalytic cycle, in substrate recruiting, chemical transformation, and product release. Conformational transitions may involve conformational selection and induced fit, which can be viewed as a special case in the catalytic network. NMR, X-ray crystallography, single-molecule FRET, and simulations clearly demonstrate that the free enzyme dynamics already encompass all the conformations necessary for substrate binding, preorganization, transition-state stabilization, and product release. Conformational selection and substate population shift at each step of the catalytic turnover can accommodate enzyme specificity and efficiency. Within such a framework, entropy can have a larger role in conformational dynamics than in direct energy transfer in dynamically promoted catalysis. C1 [Ma, Buyong; Nussinov, Ruth] SAIC Frederick Inc, Basic Sci Program, Ctr Canc Res Nanobiol Program, NCI Frederick, Ft Detrick, MD 21702 USA. [Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Dept Human Genet & Mol Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel. RP Ma, BY (reprint author), SAIC Frederick Inc, Basic Sci Program, Ctr Canc Res Nanobiol Program, NCI Frederick, Ft Detrick, MD 21702 USA. EM mabuyong@mail.nih.gov; ruthnu@helix.nih.gov RI Ma, Buyong/F-9491-2011 OI Ma, Buyong/0000-0002-7383-719X FU National Cancer Institute, National Institutes of Health [HHSN261200800001E]; NIH, NCI, Center for Cancer Research FX This project has been funded in whole or in part with Federal funds from the National Cancer Institute, National Institutes of Health, under contract number HHSN261200800001E. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. This research was supported (in part) by the Intramural Research Program of the NIH, NCI, Center for Cancer Research. NR 61 TC 110 Z9 113 U1 5 U2 63 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1367-5931 J9 CURR OPIN CHEM BIOL JI Curr. Opin. Chem. Biol. PD OCT PY 2010 VL 14 IS 5 BP 652 EP 659 DI 10.1016/j.cbpa.2010.08.012 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 676MQ UT WOS:000283916300014 PM 20822947 ER PT J AU Zhu, XG Cheng, SY AF Zhu, Xuguang Cheng, Sheue-yann TI New insights into regulation of lipid metabolism by thyroid hormone SO CURRENT OPINION IN ENDOCRINOLOGY DIABETES AND OBESITY LA English DT Article DE lipid metabolism; mouse models; mutations; thyroid hormone; thyroid hormone receptors ID BROWN ADIPOSE-TISSUE; GENE-EXPRESSION; TR-BETA; RECEPTOR; MICE; RESISTANCE; ADIPOGENESIS; MUTATION; LIVER; THERMOGENESIS AB Purpose of review Thyroid hormone (3,3',5-triiodo-L-thyronine) plays an important role in thermogenesis and maintenance of lipid homeostasis. The present article reviews the evidence that 3,3',5-triiodo-L-thyronine regulates lipid metabolism via thyroid hormone receptors, focusing particularly on in-vivo findings using genetically engineered mice. Recent findings That lipid metabolism is regulated via thyroid hormone receptor isoforms in a tissue-dependent manner was recently uncovered by using knockin mutant mice harboring an identical mutation in the Thra gene (Thra1(PV) mouse) or the Thrb gene (Thrb(PV) mouse). The mutation in the Thra gene dramatically decreases the mass of both white adipose tissue and liver. In contrast, the mutation in the Thrb gene markedly increases the mass of liver with an excess depot of lipids, but no significant abnormality is observed in white adipose tissue. Molecular studies show that the expression of lipogenic genes is decreased in white adipose tissue of Thra1(PV) mice, but not in Thrb(PV) mice. Markedly increased lipogenic enzyme expression, and decreased fatty acid beta-oxidation activity contribute to the adipogenic steatosis and lipid accumulation in the liver of Thrb(PV) mice. In contrast, reduced expression of genes critical for lipogenesis mediates decreased liver mass with lipid scarcity in Thra1(PV) mice. Summary Studies using Thra1(PV) and Thrb(PV) mice indicate that apo-thyroid hormone receptor-beta and apo-thyroid hormone receptor-alpha-1 mediate distinct deleterious effects on lipid metabolism. Thus, both thyroid hormone receptor isoforms contribute to the pathogenesis of lipid abnormalities in hypothyroidism, but in a target tissue-dependent manner. These studies suggest that thyroid hormone receptor isoform-specific ligands could be designed as therapeutic targets for lipid abnormalities. C1 [Zhu, Xuguang; Cheng, Sheue-yann] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Cheng, SY (reprint author), NCI, Mol Biol Lab, Ctr Canc Res, NIH, 37 Convent Dr,Room 5128, Bethesda, MD 20892 USA. EM chengs@mail.nih.gov FU Center for Cancer Research, National Cancer Institute, National Institutes of Health FX The present research was supported by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute, National Institutes of Health. We thank Dr Gregory Brent for critical reading of this article and for his valuable suggestions. We wish to thank all colleagues and collaborators who have contributed to the work described in this review. NR 33 TC 26 Z9 29 U1 0 U2 15 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1752-296X J9 CURR OPIN ENDOCRINOL JI Curr. Opin. Endocrinol. Diabetes Obes. PD OCT PY 2010 VL 17 IS 5 BP 408 EP 413 DI 10.1097/MED.0b013e32833d6d46 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 691FJ UT WOS:000285065400004 PM 20644471 ER PT J AU Chappert, P Schwartz, RH AF Chappert, Pascal Schwartz, Ronald H. TI Induction of T cell anergy: integration of environmental cues and infectious tolerance SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID TRANSCRIPTION FACTOR FOXP3; DENDRITIC CELLS; TGF-BETA; RETINOIC-ACID; IN-VIVO; REGULATORY CELLS; CUTTING EDGE; SIGNAL-TRANSDUCTION; IMMUNE SUPPRESSION; CYCLE PROGRESSION AB Anergy is a state of long-term hyporesponsiveness in T cells that is characterized by an active repression of TCR signaling and IL-2 expression [1] Several forms of anergy have been described and the past few years have brought to light an increasing number of anergic factors' involved in the induction and the active maintenance of the state in lymphocytes The role of mTOR and other related metabolic sensors and regulators has recently emerged as of particular importance in broadening our view of anergy-inducing signals We will discuss the role of these molecules in regulating the choice between anergy and activation a decision faced by all T cells undergoing TCR stimulation We will then explore the relationship between the induction of anergy and the induction of regulatory T cells as well as the potential crosstalk responsible for the phenomenon of infectious tolerance C1 [Chappert, Pascal; Schwartz, Ronald H.] NIAID, Cellular & Mol Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Schwartz, RH (reprint author), NIAID, Cellular & Mol Immunol Lab, NIH, 4-111 Ctr Dr MSC 0420, Bethesda, MD 20892 USA. OI chappert, pascal/0000-0002-9799-4608 FU Division of Intramural Research National Institute of Allergy and Infectious Diseases National Institutes of Health FX The authors thank Dr Nevil Singh for critical reading and helpful discussion of this review The authors were supported by the Division of Intramural Research National Institute of Allergy and Infectious Diseases National Institutes of Health NR 70 TC 53 Z9 54 U1 0 U2 7 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD OCT PY 2010 VL 22 IS 5 BP 552 EP 559 DI 10.1016/j.coi.2010.08.005 PG 8 WC Immunology SC Immunology GA 684QL UT WOS:000284564300002 PM 20869863 ER PT J AU Clatworthy, MR Espeli, M Torpey, N Smith, KGC AF Clatworthy, M. R. Espeli, M. Torpey, N. Smith, K. G. C. TI The generation and maintenance of serum alloantibody SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID FC-GAMMA-RIIB; RENAL-ALLOGRAFT RECIPIENTS; INCOMPATIBLE KIDNEY-TRANSPLANTATION; ANTIENDOTHELIAL CELL ANTIBODIES; SUBCAPSULAR SINUS MACROPHAGES; FOLLICULAR DENDRITIC CELLS; HUMORAL IMMUNE-RESPONSE; DONOR-SPECIFIC ANTIBODY; CLASS-I ALLOANTIGENS; HLA-DR PHENOTYPE AB Donor-specific alloantibodies (DSA) mediate hyperacute and acute antibody-mediated rejection (AMR) which can lead to early graft damage and loss and are also associated with chronic AMR and reduced long-term graft survival Such alloantibodies can be generated by previous exposure to major histocompatibility (MHC)antigens (usually via blood transfusions previous allografts or pregnancy) or can occur de novo after transplantation Recent studies also suggest that non-MHC antibodies including those recognising major histocompatibility complex class l-related chain A (MICA) MICB, vimentin angiotensin II type I receptor may also have an adverse impact on allograft outcomes In this review we consider how the dose route and context of antigen exposure influences DSA induction and describe factors which control the generation maintenance and survival of alloantibody-producing plasma cells Finally we discuss the implications of these variables on therapeutic approaches to DSA C1 [Clatworthy, M. R.; Espeli, M.; Smith, K. G. C.] Univ Cambridge, Cambridge Inst Med Res, Sch Clin Med, Cambridge CB2 0XY, England. [Clatworthy, M. R.; Espeli, M.; Torpey, N.; Smith, K. G. C.] Univ Cambridge, Cambridge Sch Clin Med, Dept Med, Cambridge CB2 0XY, England. [Clatworthy, M. R.] NIAID, Lymphocyte Biol Sect, NIH, Bethesda, MD 20892 USA. RP Smith, KGC (reprint author), Univ Cambridge, Cambridge Inst Med Res, Sch Clin Med, Box 139 Addenbrookes Hosp Hills Rd, Cambridge CB2 0XY, England. FU Wellcome Trust [081020] NR 124 TC 19 Z9 19 U1 1 U2 3 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD OCT PY 2010 VL 22 IS 5 BP 669 EP 681 DI 10.1016/j.coi.2010.08.018 PG 13 WC Immunology SC Immunology GA 684QL UT WOS:000284564300018 PM 20932734 ER PT J AU Renvoise, B Blackstone, C AF Renvoise, Benoit Blackstone, Craig TI Emerging themes of ER organization in the development and maintenance of axons SO CURRENT OPINION IN NEUROBIOLOGY LA English DT Article ID HEREDITARY SPASTIC PARAPLEGIA; SMOOTH ENDOPLASMIC-RETICULUM; AMYOTROPHIC-LATERAL-SCLEROSIS; GREEN FLUORESCENT PROTEIN; MEMBRANE-PROTEINS; CONTINUOUS NETWORK; CALCIUM STORES; ANIMAL-CELLS; NEURONS; ATLASTIN AB The endoplasmic reticulum (ER) is a continuous membrane system comprising the nuclear envelope, polyribosome-studded peripheral sheets, and a polygonal network of smooth tubules extending throughout the cell. Though protein biosynthesis, transport, and quality control in the ER have been extensively studied, mechanisms underlying the heterogeneous architecture of the ER have been clarified more recently. These insights have increased interest in ER morphology changes associated with the development of neuronal axons and dendrites as well as their integration with presynaptic and postsynaptic signaling pathways. A number of proteins involved in shaping and distributing the ER network are mutated in neurological disorders, particularly the hereditary spastic paraplegias, emphasizing the importance of proper ER morphology for the establishment and maintenance of highly polarized neurons. C1 [Renvoise, Benoit; Blackstone, Craig] NINDS, Cellular Neurol Unit, Neurogenet Branch, NIH, Bethesda, MD 20892 USA. RP Blackstone, C (reprint author), NINDS, Cellular Neurol Unit, Neurogenet Branch, NIH, Bethesda, MD 20892 USA. EM blackstc@ninds.nih.gov FU National Institute of Neurological Disorders and Stroke, National Institutes of Health FX This research was supported by the Intramural Research Program of the National Institute of Neurological Disorders and Stroke, National Institutes of Health. NR 57 TC 23 Z9 24 U1 1 U2 11 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-4388 J9 CURR OPIN NEUROBIOL JI Curr. Opin. Neurobiol. PD OCT PY 2010 VL 20 IS 5 BP 531 EP 537 DI 10.1016/j.conb.2010.07.001 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 671DS UT WOS:000283481100002 PM 20678923 ER PT J AU Ramakrishnan, B Qasba, PK AF Ramakrishnan, Boopathy Qasba, Pradman K. TI Structure-based evolutionary relationship of glycosyltransferases: a case study of vertebrate beta 1,4-galactosyltransferase, invertebrate beta 1,4-N-acetylgalactosaminyltransferase and alpha-polypeptidyl-N-acetylgalactosaminyltransferase SO CURRENT OPINION IN STRUCTURAL BIOLOGY LA English DT Review ID EHLERS-DANLOS-SYNDROME; UDP-GALNAC; CAENORHABDITIS-ELEGANS; ENZYMATIC CHARACTERIZATION; DROSOPHILA-MELANOGASTER; LACTOSE SYNTHETASE; MOLECULAR-CLONING; GENE; BETA; IDENTIFICATION AB Cell surface glycans play important cellular functions and are synthesized by glycosyltransferases Structure and function studies show that the donor sugar specificity of the invertebrate beta 1,4-N-acetyl-glactosaminyltransferase (beta 4GaINAc-T) and the vertebrate beta 1 4-galactosyltransferase I (beta 4Gal-T1) are related by a single amino acid residue change Comparison of the catalytic domain crystal structures of the beta 4Gal-T1 and the alpha-polypeptidyl-GaINAc-T (alpha ppGaINAc-T) shows that their protein structure and sequences are similar Therefore, it seems that the invertebrate beta 4GaINAc-T and the catalytic domain of alpha ppGaINAc-T might have emerged from a common primordial gene When vertebrates emerged from invertebrates the amino acid that determines the donor sugar specificity of the invertebrate beta 4GaINAc-T might have mutated thus converting the enzyme to a beta 4Gal-T1 in vertebrates C1 [Ramakrishnan, Boopathy; Qasba, Pradman K.] NCI, Struct Glycobiol Sect, Ctr Canc Res, Nanobiol Program, Frederick, MD 21702 USA. [Ramakrishnan, Boopathy] NCI, Basic Res Program, SAIC Frederick Inc, Ctr Canc Res,Nanobiol Program, Frederick, MD 21702 USA. RP Qasba, PK (reprint author), NCI, Struct Glycobiol Sect, Ctr Canc Res, Nanobiol Program, Frederick, MD 21702 USA. FU National Cancer Institute National Institutes of Health [HHSN261(sic)00800001E]; NIH National Cancer Institute Center for Cancer Research FX We thank Dr Nathan Sharon from Weizmann Institute of Science Israel for encouraging us to write this review and for his valuable comments on the manuscript The writing of this review was funded in whole or in part with Federal funds from the National Cancer Institute National Institutes of Health under contract HHSN261(sic)00800001E The content of this publication does not necessarily reflect the view or policies of the Department of Health and Human Services nor does mention of trade names commercial products or organizations imply endorsement by the US government This research was supported [in part] by the Intramural Research Program of the NIH National Cancer Institute Center for Cancer Research NR 42 TC 5 Z9 5 U1 1 U2 5 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-440X J9 CURR OPIN STRUC BIOL JI Curr. Opin. Struct. Biol. PD OCT PY 2010 VL 20 IS 5 BP 536 EP 542 DI 10.1016/j.sbi.2010.07.004 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 686DL UT WOS:000284676900002 PM 20705453 ER PT J AU Chruszcz, M Domagalski, M Osinski, T Wlodawer, A Minor, W AF Chruszcz, Maksymilian Domagalski, Marcin Osinski, Tomasz Wlodawer, Alexander Minor, Wladek TI Unmet challenges of structural genomics SO CURRENT OPINION IN STRUCTURAL BIOLOGY LA English DT Article ID PROTEIN CRYSTALLIZATION; DRUG DISCOVERY; ANTIBACTERIAL DISCOVERY; THERMOTOGA-MARITIMA; RE-REFINEMENT; PREDICTION; DATABASE; PDB; CRYSTALLOGRAPHY; OPTIMIZATION AB Structural genomics (SG) programs have developed during the last decade many novel methodologies for faster and more accurate structure determination These new tools and approaches led to the determination of thousands of protein structures The generation of enormous amounts of experimental data resulted in significant improvements in the understanding of many biological processes at molecular levels However the amount of data collected so far is so large that traditional analysis methods are limiting the rate of extraction of biological and biochemical information from 3D models This situation has prompted us to review the challenges that remain unmet by SG, as well as the areas in which the potential impact of SG could exceed what has been achieved so far C1 [Chruszcz, Maksymilian; Domagalski, Marcin; Osinski, Tomasz; Minor, Wladek] Univ Virginia, Dept Mol Physiol & Biol Phys, Charlottesville, VA 22908 USA. [Wlodawer, Alexander] NCI, Prot Struct Sect, Macromol Crystallog Lab, Frederick, MD 21702 USA. RP Minor, W (reprint author), Univ Virginia, Dept Mol Physiol & Biol Phys, 1340 Jefferson Pk, Charlottesville, VA 22908 USA. RI Chruszcz, Maksymilian/E-6407-2011; Minor, Wladek/F-3096-2014; OI Chruszcz, Maksymilian/0000-0001-7521-5485; Minor, Wladek/0000-0001-7075-7090 FU National Institute of Allergy and Infectious Diseases [GM74942, GM53163]; National Institutes of Health Department of Health and Human Services [HHSN272200700058O]; NIH National Cancer Institute Center for Cancer Research FX The authors would like to thank Matthew Zimmerman Ian Wilson Jack Johnson Tom Ierwilliger Steve Almo Samar Hasnain Wayne Anderson Andizej Joachimiak Zbyszek Dauter and Heping Zheng for valuable comments on the manuscript We especially thank Dr Almo for turning our attention to structure libraries used for modeling studies This work was supported by grants GM74942 GM53163 with Federal funds from the National Institute of Allergy and Infectious Diseases National Institutes of Health Department of Health and Human Services under Contract No HHSN272200700058O and by the Intramural Research Program of the NIH National Cancer Institute Center for Cancer Research NR 80 TC 22 Z9 24 U1 0 U2 12 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-440X J9 CURR OPIN STRUC BIOL JI Curr. Opin. Struct. Biol. PD OCT PY 2010 VL 20 IS 5 BP 587 EP 597 DI 10.1016/j.sbi.2010.08.001 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 686DL UT WOS:000284676900009 PM 20810277 ER PT J AU Grothaus, PG Cragg, GM Newman, DJ AF Grothaus, Paul G. Cragg, Gordon M. Newman, David J. TI Plant Natural Products in Anticancer Drug Discovery SO CURRENT ORGANIC CHEMISTRY LA English DT Article DE Plant-derived natural products; anticancer; antitumor; targeted agents; endophytes ID ARYL-HYDROCARBON RECEPTOR; CYCLIN-DEPENDENT KINASES; ENDOPHYTIC FUNGUS; ANTINEOPLASTIC AGENTS; ANTITUMOR-ACTIVITY; CLINICAL-TRIALS; CELL-LINES; IN-VITRO; CANCER; ACTIVATION AB Plant-derived natural products have been an important source of several clinically useful anti-cancer agents. Plants continue to play a major role in drug discovery as evidenced by the number of promising new agents in clinical development based on selective activity against cancer-related molecular targets. Due to improvements in tumor targeting technology, some agents which failed in earlier clinical studies are also stimulating renewed interest. We wish to draw the attention of readers to the rapidly evolving recognition that a significant number of natural product drugs/leads are possibly produced by endophytic fungi and microbes residing in the plant tissues. We consider that this area of natural product research should be expanded significantly. C1 [Grothaus, Paul G.; Cragg, Gordon M.; Newman, David J.] NCI, Nat Prod Branch, Dev Therapeut Program, Div Canc Treatment & Diag,Fairview Ctr, Frederick, MD 21702 USA. RP Grothaus, PG (reprint author), NCI, Nat Prod Branch, Dev Therapeut Program, Div Canc Treatment & Diag,Fairview Ctr, Suite 206,POB B, Frederick, MD 21702 USA. EM grothausp@mail.nih.gov NR 93 TC 18 Z9 19 U1 3 U2 36 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1385-2728 J9 CURR ORG CHEM JI Curr. Org. Chem. PD OCT PY 2010 VL 14 IS 16 BP 1781 EP 1791 PG 11 WC Chemistry, Organic SC Chemistry GA 688BY UT WOS:000284825800009 ER PT J AU Trinchieri, G Gyulai, Z Salcedo, R Jones, Y Lyakh, L Pickett, RW Smith, L Dai, RM Mason, A Cataisson, C Yuspa, S AF Trinchieri, Giorgio Gyulai, Zsofia Salcedo, Rosalba Jones, Yava Lyakh, Lyudmila Pickett, Robin Winkler Smith, Loretta Dai, Ren Ming Mason, Anna Cataisson, Christophe Yuspa, Stuart TI Innate resistance, inflammation, and carcinogenesis SO CYTOKINE LA English DT Meeting Abstract CT 8th Joint Conference of the International-Cytokine-Society/International-Society-for-and-Cytokine-Re search CY OCT 03-07, 2010 CL Chicago, IL SP Int Cytokine Soc, Int Soc Interferon & Cytokine Res C1 [Trinchieri, Giorgio; Gyulai, Zsofia; Salcedo, Rosalba; Jones, Yava; Lyakh, Lyudmila; Pickett, Robin Winkler; Smith, Loretta; Dai, Ren Ming; Mason, Anna] NCI, Canc & Inflammat Program, CCR, Frederick, MD 21701 USA. [Cataisson, Christophe; Yuspa, Stuart] NCI, Cell Biol & Genet Lab, CCR, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD OCT-NOV PY 2010 VL 52 IS 1-2 SI SI BP 1 EP 1 DI 10.1016/j.cyto.2010.07.010 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 657NC UT WOS:000282418400002 ER PT J AU Hodge, DL Berthet, C Subleski, J Coppola, V Shirota, H Buschman, M Razzook, C Young, HA AF Hodge, Deborah L. Berthet, Cyril Subleski, Jeff Coppola, Vincenzo Shirota, Hidekazu Buschman, Matthew Razzook, Catherine Young, Howard A. TI Targeted removal of IFN-gamma 3 ' untranslated region AU-rich element alters B cell function resulting in lupus-like disease in C57BL6 mice SO CYTOKINE LA English DT Meeting Abstract CT 8th Joint Conference of the International-Cytokine-Society/International-Society-for-and-Cytokine-Re search CY OCT 03-07, 2010 CL Chicago, IL SP Int Cytokine Soc, Int Soc Interferon & Cytokine Res C1 [Hodge, Deborah L.; Subleski, Jeff; Shirota, Hidekazu; Buschman, Matthew; Razzook, Catherine; Young, Howard A.] NCI, Expt Immunol Lab, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21702 USA. [Berthet, Cyril; Coppola, Vincenzo] NCI, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21702 USA. RI Coppola, Vincenzo/E-2917-2011 OI Coppola, Vincenzo/0000-0001-6163-1779 NR 0 TC 0 Z9 0 U1 0 U2 2 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD OCT-NOV PY 2010 VL 52 IS 1-2 SI SI BP 5 EP 5 DI 10.1016/j.cyto.2010.07.025 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 657NC UT WOS:000282418400013 ER PT J AU Durum, SK Li, WQ Hixon, JA Felber, B Steidler, L Hanson, ML AF Durum, Scott K. Li, Wen Qing Hixon, Julie A. Felber, Barbara Steidler, Lothar Hanson, Miranda L. TI Lactococcus lactis expressing IL-27: Therapeutic promise in inflammatory bowel disease SO CYTOKINE LA English DT Meeting Abstract CT 8th Joint Conference of the International-Cytokine-Society/International-Society-for-and-Cytokine-Re search CY OCT 03-07, 2010 CL Chicago, IL SP Int Cytokine Soc, Int Soc Interferon & Cytokine Res C1 [Durum, Scott K.; Li, Wen Qing; Hixon, Julie A.; Felber, Barbara; Hanson, Miranda L.] NCI, Frederick, MD 21701 USA. [Steidler, Lothar] ActoGenix, Ghent, Belgium. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD OCT-NOV PY 2010 VL 52 IS 1-2 SI SI BP 11 EP 11 DI 10.1016/j.cyto.2010.07.048 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 657NC UT WOS:000282418400033 ER PT J AU Ozato, K Sarai, N Patel, M Ayithan, N Tamura, T AF Ozato, Keiko Sarai, Naoyuki Patel, Mira Ayithan, Natarajan Tamura, Tomohiko TI Chromatin dynamics in interferon signaling: Analysis of the histone H3.3 deposition SO CYTOKINE LA English DT Meeting Abstract CT 8th Joint Conference of the International-Cytokine-Society/International-Society-for-and-Cytokine-Re search CY OCT 03-07, 2010 CL Chicago, IL SP Int Cytokine Soc, Int Soc Interferon & Cytokine Res C1 [Ozato, Keiko; Sarai, Naoyuki; Patel, Mira; Ayithan, Natarajan] NICHD, Program Genom Differentiat, NIH, Bethesda, MD USA. [Tamura, Tomohiko] Yokohama City Univ, Sch Med, Yokohama, Kanagawa 232, Japan. RI Patel, Mira/A-3013-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD OCT-NOV PY 2010 VL 52 IS 1-2 SI SI BP 15 EP 15 DI 10.1016/j.cyto.2010.07.065 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 657NC UT WOS:000282418400048 ER PT J AU Patel, M Debrosse, M Smith, M Dev, A WalterHuynh Tamura, T Heightman, T Ozato, K AF Patel, Mira Debrosse, Maxime Smith, Matthew Dev, Anup WalterHuynh Tamura, Tomohiko Heightman, Tom Ozato, Keiko TI Transcriptional regulation of interferon stimulated genes: Role of chromatin binding protein Brd4 SO CYTOKINE LA English DT Meeting Abstract CT 8th Joint Conference of the International-Cytokine-Society/International-Society-for-and-Cytokine-Re search CY OCT 03-07, 2010 CL Chicago, IL SP Int Cytokine Soc, Int Soc Interferon & Cytokine Res C1 [Patel, Mira; Debrosse, Maxime; Smith, Matthew; Dev, Anup; WalterHuynh; Ozato, Keiko] NICHD, Program Genom Differentiat, NIH, Bethesda, MD USA. [Tamura, Tomohiko] Yokohama City Univ, Sch Med, Yokohama, Kanagawa, Japan. [Heightman, Tom] Univ Oxford, Struct Genom Consortium, Oxford, England. RI Patel, Mira/A-3013-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD OCT-NOV PY 2010 VL 52 IS 1-2 SI SI BP 16 EP 16 DI 10.1016/j.cyto.2010.07.071 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 657NC UT WOS:000282418400054 ER PT J AU Oopenheim, PJ Tewary, P de la Rosa, G De Yang, AF Oopenheim, Post J. Tewary, Poonam de la Rosa, Gonzalo De Yang TI Alarmins activate immune responses by inducing dendritic cell chemotaxis and maturation SO CYTOKINE LA English DT Meeting Abstract CT 8th Joint Conference of the International-Cytokine-Society/International-Society-for-and-Cytokine-Re search CY OCT 03-07, 2010 CL Chicago, IL SP Int Cytokine Soc, Int Soc Interferon & Cytokine Res C1 [Oopenheim, Post J.; Tewary, Poonam; de la Rosa, Gonzalo] NCI Frederick, CCR, C1P, Mol Immunoregulat Lab, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD OCT-NOV PY 2010 VL 52 IS 1-2 SI SI BP 19 EP 19 DI 10.1016/j.cyto.2010.07.084 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 657NC UT WOS:000282418400066 ER PT J AU Rachman, Y Leonard, WJ AF Rachman, Yrina Leonard, Warren J. TI The importance of STAT5 activation in thymic stromal lymphopoietin mediated signaling in mouse and human T cells SO CYTOKINE LA English DT Meeting Abstract CT 8th Joint Conference of the International-Cytokine-Society/International-Society-for-and-Cytokine-Re search CY OCT 03-07, 2010 CL Chicago, IL SP Int Cytokine Soc, Int Soc Interferon & Cytokine Res C1 [Rachman, Yrina; Leonard, Warren J.] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD OCT-NOV PY 2010 VL 52 IS 1-2 SI SI BP 20 EP 20 DI 10.1016/j.cyto.2010.07.086 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 657NC UT WOS:000282418400068 ER PT J AU Hanson, ML Nixon, JA Li, WQ Felber, BK Anver, MR Steidler, L Durum, SK AF Hanson, Miranda L. Nixon, Julie A. Li, Wenqing Felber, Barbara K. Anver, Miriam R. Steidler, Lothar Durum, Scott K. TI Lactococcus lactis expressing IL-27: A potential therapeutic for inflammatory bowel disease SO CYTOKINE LA English DT Meeting Abstract CT 8th Joint Conference of the International-Cytokine-Society/International-Society-for-and-Cytokine-Re search CY OCT 03-07, 2010 CL Chicago, IL SP Int Cytokine Soc, Int Soc Interferon & Cytokine Res C1 [Hanson, Miranda L.; Nixon, Julie A.; Li, Wenqing; Durum, Scott K.] NCI, Mol Immunoregulat Lab, Canc Inflammat Program, Ctr Canc Res, Frederick, MD 21701 USA. [Felber, Barbara K.] NCI, Human Retrovirus Pathogenesis Sect, Vaccine Branch, Ctr Canc Res, Frederick, MD 21701 USA. [Anver, Miriam R.] NCI, LASP, SAIC, Ctr Canc Res, Frederick, MD 21701 USA. [Steidler, Lothar] ActoGenix NV, Zwijnaarde, Belgium. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD OCT-NOV PY 2010 VL 52 IS 1-2 SI SI BP 22 EP 23 DI 10.1016/j.cyto.2010.07.099 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 657NC UT WOS:000282418400081 ER PT J AU Puronen, CE Thompson, WL Imamichi, H Beq, S Hodge, JN Rehm, C DerSimonian, R Brenchley, JM Sereti, I AF Puronen, Camille E. Thompson, William L. Imamichi, Hiromi Beq, Stephanie Hodge, Jessica N. Rehm, Catherine DerSimonian, Rebecca Brenchley, Jason M. Sereti, Irini TI Decreased IL-7 responsiveness of T lymphocytes in patients with idiopathic CD4 lymphopenia SO CYTOKINE LA English DT Meeting Abstract CT 8th Joint Conference of the International-Cytokine-Society/International-Society-for-and-Cytokine-Re search CY OCT 03-07, 2010 CL Chicago, IL SP Int Cytokine Soc, Int Soc Interferon & Cytokine Res C1 [Puronen, Camille E.; Thompson, William L.; Imamichi, Hiromi; Hodge, Jessica N.; Rehm, Catherine; Sereti, Irini] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. [Beq, Stephanie] Cytheris, Issy Les Moulineaux, France. [DerSimonian, Rebecca] NIAID, Biostat Branch, NIH, Bethesda, MD 20892 USA. [Brenchley, Jason M.] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD OCT-NOV PY 2010 VL 52 IS 1-2 SI SI BP 23 EP 24 DI 10.1016/j.cyto.2010.07.104 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 657NC UT WOS:000282418400086 ER PT J AU Liu, Y Yang, Y Yao, XH Huang, JA Gong, WH Chen, KQ Bian, XW Wang, JM AF Liu, Ying Yang, Yan Yao, Xiaohong Huang, Jian Gong, Wanghua Chen, Keqiang Bian, Xiuwu Wang, Ji Ming TI Identification of Annexin 1 (Anx A1) as a necrotic glioblastoma cell-derived chemotactic agonist for the G protein-coupled receptor FPR (FPR1) SO CYTOKINE LA English DT Meeting Abstract CT 8th Joint Conference of the International-Cytokine-Society/International-Society-for-and-Cytokine-Re search CY OCT 03-07, 2010 CL Chicago, IL SP Int Cytokine Soc, Int Soc Interferon & Cytokine Res C1 [Liu, Ying; Yang, Yan; Chen, Keqiang; Wang, Ji Ming] NCI, Mol Immunoregulat Lab, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21702 USA. [Yang, Yan] Ocean Univ China, Coll Marine Life Sci, Qingdao 266003, Peoples R China. [Yao, Xiaohong; Huang, Jian; Bian, Xiuwu] Third Mil Med Univ, Dept Pathophysiol, Chongqing 400038, Peoples R China. [Yao, Xiaohong; Huang, Jian; Bian, Xiuwu] Third Mil Med Univ, Inst Pathol, Chongqing 400038, Peoples R China. [Gong, Wanghua] SAIC Frederick, Basic Res Program, Frederick, MD 21702 USA. RI Bian, Xiuwu/F-1569-2011; Bian, Xiu-wu/D-4736-2017 OI Bian, Xiu-wu/0000-0003-4383-0197 NR 0 TC 0 Z9 0 U1 0 U2 2 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD OCT-NOV PY 2010 VL 52 IS 1-2 SI SI BP 24 EP 25 DI 10.1016/j.cyto.2010.07.108 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 657NC UT WOS:000282418400090 ER PT J AU Sisler, JD Szelag, M Potla, R Zhang, QF Szczepanek, K Derecka, M Wegrzyn, J Dulak, J Zou, WX Hamed, H Shutt, T Cichy, J Chen, XM Baker, DP Dent, P Feldman, GM Shadel, G Larner, AC AF Sisler, Jennifer D. Szelag, Magdalena Potla, Ramesh Zhang, Qifang Szczepanek, Karol Derecka, Marta Wegrzyn, Joanna Dulak, Jozef Zou, Wenxin Hamed, Hossein Shutt, Timothy Cichy, Joanna Chen, Xiaomin Baker, Darren P. Dent, Paul Feldman, Gerald M. Shadel, Gerald Larner, Andrew C. TI The role of STAT1 in regulation of mitochondrial gene expression SO CYTOKINE LA English DT Meeting Abstract CT 8th Joint Conference of the International-Cytokine-Society/International-Society-for-and-Cytokine-Re search CY OCT 03-07, 2010 CL Chicago, IL SP Int Cytokine Soc, Int Soc Interferon & Cytokine Res C1 [Sisler, Jennifer D.; Szelag, Magdalena; Zhang, Qifang; Szczepanek, Karol; Derecka, Marta; Wegrzyn, Joanna; Hamed, Hossein; Dent, Paul; Larner, Andrew C.] Virginia Commonwealth Univ, Dept Biochem & Mol Biol, Richmond, VA 23298 USA. [Sisler, Jennifer D.; Szelag, Magdalena; Zhang, Qifang; Szczepanek, Karol; Derecka, Marta; Wegrzyn, Joanna; Hamed, Hossein; Dent, Paul; Larner, Andrew C.] Virginia Commonwealth Univ, Massey Canc Ctr, Richmond, VA 23298 USA. [Potla, Ramesh] Natl Inst Neurol Disorders & Stroke, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. [Szelag, Magdalena; Szczepanek, Karol; Wegrzyn, Joanna; Dulak, Jozef] Jagiellonian Univ, Dept Med Biotechnol, Fac Biochem Biophys & Biotechnol, Krakow, Poland. [Zou, Wenxin; Chen, Xiaomin] Univ Texas MD Anderson Canc Ctr, Dept Biochem & Mol Biol, Houston, TX 77030 USA. [Shutt, Timothy; Shadel, Gerald] Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06520 USA. [Baker, Darren P.] Biogen Idec Inc, Cambridge Ctr 14, Cambridge, MA 02142 USA. [Feldman, Gerald M.; Larner, Andrew C.] US FDA, Lab Mol & Dev Immunol, Div Monoclonal Antibodies, Off Biotechnol Prod,CDER, Bethesda, MD 20892 USA. [Derecka, Marta; Cichy, Joanna] Jagiellonian Univ, Dept Immunol, Fac Biochem Biophys & Biotechnol, Krakow, Poland. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD OCT-NOV PY 2010 VL 52 IS 1-2 SI SI BP 29 EP 29 DI 10.1016/j.cyto.2010.07.130 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 657NC UT WOS:000282418400112 ER PT J AU Morrow, AN Schmeisser, H Tsuno, T Zoon, KC AF Morrow, A. N. Schmeisser, H. Tsuno, T. Zoon, K. C. TI Role for ISGF3 in the antiviral activity of interferon gamma SO CYTOKINE LA English DT Meeting Abstract CT 8th Joint Conference of the International-Cytokine-Society/International-Society-for-and-Cytokine-Re search CY OCT 03-07, 2010 CL Chicago, IL SP Int Cytokine Soc, Int Soc Interferon & Cytokine Res C1 [Morrow, A. N.; Schmeisser, H.; Tsuno, T.; Zoon, K. C.] NIAID, Cytokine Biol Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD OCT-NOV PY 2010 VL 52 IS 1-2 SI SI BP 30 EP 31 DI 10.1016/j.cyto.2010.07.136 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 657NC UT WOS:000282418400118 ER PT J AU Dickensheets, H Sheikh, F Pos, Z Marincola, F Donnelly, RP AF Dickensheets, Harold Sheikh, Faruk Pos, Zoltan Marincola, Francesco Donnelly, Raymond P. TI COmparative analysis of responsiveness to IFN-alpha and IFN-lambda by normal human bronchial epithelial cells and hepatocytes SO CYTOKINE LA English DT Meeting Abstract CT 8th Joint Conference of the International-Cytokine-Society/International-Society-for-and-Cytokine-Re search CY OCT 03-07, 2010 CL Chicago, IL SP Int Cytokine Soc, Int Soc Interferon & Cytokine Res C1 [Dickensheets, Harold; Sheikh, Faruk; Donnelly, Raymond P.] US FDA, Ctr Drug Evaluat & Res, Div Therapeut Proteins, Bethesda, MD 20014 USA. [Pos, Zoltan; Marincola, Francesco] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD OCT-NOV PY 2010 VL 52 IS 1-2 SI SI BP 34 EP 34 DI 10.1016/j.cyto.2010.07.151 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 657NC UT WOS:000282418400133 ER PT J AU Savan, R Legiewicz, M Bindewald, E McFarland, AP Orr, S Schwerk, J Yalamanchili, R Hakim, S Kronfli, A Ramakrishnan, K Anderson, S Shapiro, B LeGrice, S Young, HA AF Savan, Ram Legiewicz, Michal Bindewald, Eckart McFarland, Adelle P. Orr, Selinda Schwerk, Johannes Yalamanchili, Rajesh Hakim, Shakeeb Kronfli, Anthony Ramakrishnan, Karthika Anderson, Stephen Shapiro, Bruce LeGrice, Stuart Young, Howard A. TI miRNA interacts with AU-rich elements stabilizing interferon gamma gene SO CYTOKINE LA English DT Meeting Abstract CT 8th Joint Conference of the International-Cytokine-Society/International-Society-for-and-Cytokine-Re search CY OCT 03-07, 2010 CL Chicago, IL SP Int Cytokine Soc, Int Soc Interferon & Cytokine Res C1 [Savan, Ram; McFarland, Adelle P.; Orr, Selinda; Schwerk, Johannes; Yalamanchili, Rajesh; Hakim, Shakeeb; Kronfli, Anthony; Ramakrishnan, Karthika; Anderson, Stephen; Young, Howard A.] NIH, Canc & Inflammat Program, Expt Immunol Lab, Ctr Canc Res, Frederick, MD USA. [Legiewicz, Michal; LeGrice, Stuart] NCI, HIV Drug Resistance Program, Ctr Canc Res, Frederick, MD 21701 USA. [Bindewald, Eckart; Shapiro, Bruce] NCI, Nanobiol Program, Ctr Canc Res, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD OCT-NOV PY 2010 VL 52 IS 1-2 SI SI BP 38 EP 39 DI 10.1016/j.cyto.2010.07.160 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 657NC UT WOS:000282418400146 ER PT J AU Baron, S Finbloom, J Horowitz, J Bekisz, J Morrow, A Zhao, TM Fey, S Schmeisser, H Balinski, C Zoon, K AF Baron, Samuel Finbloom, Joel Horowitz, Julie Bekisz, Joe Morrow, Angel Zhao, Tongmao Fey, Sam Schmeisser, Hana Balinski, Corey Zoon, Kathryn TI Antiproliferative activity of interferon activated monocytes against high concentrations of human tumor cells SO CYTOKINE LA English DT Meeting Abstract CT 8th Joint Conference of the International-Cytokine-Society/International-Society-for-and-Cytokine-Re search CY OCT 03-07, 2010 CL Chicago, IL SP Int Cytokine Soc, Int Soc Interferon & Cytokine Res C1 [Baron, Samuel; Finbloom, Joel; Horowitz, Julie; Bekisz, Joe; Morrow, Angel; Zhao, Tongmao; Fey, Sam; Schmeisser, Hana; Balinski, Corey; Zoon, Kathryn] NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD OCT-NOV PY 2010 VL 52 IS 1-2 SI SI BP 41 EP 41 DI 10.1016/j.cyto.2010.07.174 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 657NC UT WOS:000282418400153 ER PT J AU Zhang, X Brann, TW Lidie, KB Zhou, M Oguariri, RM Yang, J Fullmer, B Zheng, X Degray, GS Imamichi, H Huang, DW Lempicki, RA Baseler, MW Veenstra, TD Young, HA Lane, HC Imamichi, T AF Zhang, Xing Brann, Terrence W. Lidie, Kristy B. Zhou, Ming Oguariri, Raphael M. Yang, Jun Fullmer, Brandie Zheng, Xin Degray, Gerald S. Imamichi, Hiromi Huang, Da-Wei Lempicki, Richard A. Baseler, Michael W. Veenstra, Timothy D. Young, Howard A. Lane, H. Clifford Imamichi, Tomozumi TI Ku70 is a novel cytosolic DNA sensor and induces type-III IFN rather than Type-I IFN SO CYTOKINE LA English DT Meeting Abstract CT 8th Joint Conference of the International-Cytokine-Society/International-Society-for-and-Cytokine-Re search CY OCT 03-07, 2010 CL Chicago, IL SP Int Cytokine Soc, Int Soc Interferon & Cytokine Res C1 [Zhang, Xing; Brann, Terrence W.; Lidie, Kristy B.; Oguariri, Raphael M.; Imamichi, Tomozumi] NCI, Lab Human Retrovirol, Clin Serv Program, Appl & Dev Directorate,SAIC Frederick Inc, Frederick, MD 21701 USA. [Zhou, Ming; Veenstra, Timothy D.] NCI, Lab Proteom & Analyt Technol, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21701 USA. [Yang, Jun; Fullmer, Brandie; Zheng, Xin; Huang, Da-Wei; Lempicki, Richard A.] NCI, Lab Immunopathogenesis & Bioinformat, CSP, ADD,SAIC Frederick Inc, Frederick, MD 21701 USA. [Degray, Gerald S.] NCI, Virus Isolat Lab, CSP, ADD,SAIC Frederick Inc, Frederick, MD 21701 USA. [Imamichi, Hiromi; Lane, H. Clifford] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. [Baseler, Michael W.] NCI, AIDS Monitoring Lab, CSP, ADD,SAIC Frederick Inc, Frederick, MD 21701 USA. [Young, Howard A.] NCI, Expt Immunol Lab, Ctr Canc Res, Frederick, MD 21701 USA. RI Lempicki, Richard/E-1844-2012 OI Lempicki, Richard/0000-0002-7059-409X NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD OCT-NOV PY 2010 VL 52 IS 1-2 SI SI BP 42 EP 43 DI 10.1016/j.cyto.2010.07.179 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 657NC UT WOS:000282418400157 ER PT J AU Soender, SU Saret, S Tang, WH Paun, A Claudio, E Siebenlist, U AF Soender, Soeren U. Saret, Sun Tang, Wanhu Paun, Andrea Claudio, Estefania Siebenlist, Ulrich TI IL-17A signaling: Roles of NF-kappa B and the adaptor protein CIKS SO CYTOKINE LA English DT Meeting Abstract CT 8th Joint Conference of the International-Cytokine-Society/International-Society-for-and-Cytokine-Re search CY OCT 03-07, 2010 CL Chicago, IL SP Int Cytokine Soc, Int Soc Interferon & Cytokine Res C1 [Soender, Soeren U.; Saret, Sun; Tang, Wanhu; Paun, Andrea; Claudio, Estefania; Siebenlist, Ulrich] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD OCT-NOV PY 2010 VL 52 IS 1-2 SI SI BP 59 EP 59 DI 10.1016/j.cyto.2010.07.248 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 657NC UT WOS:000282418400224 ER PT J AU Kubota, T Kubota, M Xu, S Takeda, M Shuai, K Kato, A Ozato, K AF Kubota, Toru Kubota, Mayumi Xu, Sean Takeda, Makoto Shuai, Ke Kato, Atsushi Ozato, Keiko TI PIASy inhibits virus induced Type I interferon production SO CYTOKINE LA English DT Meeting Abstract CT 8th Joint Conference of the International-Cytokine-Society/International-Society-for-and-Cytokine-Re search CY OCT 03-07, 2010 CL Chicago, IL SP Int Cytokine Soc, Int Soc Interferon & Cytokine Res C1 [Kubota, Toru; Takeda, Makoto; Kato, Atsushi] Natl Inst Infect Dis, Dept Virol 3, Tokyo, Japan. [Kubota, Mayumi] Natl Inst Infect Dis, Dept Bacterial Pathogenesis & Infect Control, Tokyo, Japan. [Xu, Sean; Ozato, Keiko] NICHHD, NIH, Bethesda, MD 20892 USA. [Shuai, Ke] Univ Calif, Dept Biol Chem, Angels, CA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD OCT-NOV PY 2010 VL 52 IS 1-2 SI SI BP 60 EP 60 DI 10.1016/j.cyto.2010.07.253 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 657NC UT WOS:000282418400229 ER PT J AU Clark, CR Schmeisser, H Mejido, J Balinsky, CA Morrow, AN Zhao, T Zoon, KC AF Clark, Christopher R. Schmeisser, H. Mejido, J. Balinsky, C. A. Morrow, A. N. Zhao, T. Zoon, K. C. TI Characterization of IFIT3 as a novel antiviral protein SO CYTOKINE LA English DT Meeting Abstract CT 8th Joint Conference of the International-Cytokine-Society/International-Society-for-and-Cytokine-Re search CY OCT 03-07, 2010 CL Chicago, IL SP Int Cytokine Soc, Int Soc Interferon & Cytokine Res C1 [Clark, Christopher R.; Schmeisser, H.; Mejido, J.; Balinsky, C. A.; Morrow, A. N.; Zhao, T.; Zoon, K. C.] NIAID, Cytokine Biol Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD OCT-NOV PY 2010 VL 52 IS 1-2 SI SI BP 62 EP 62 DI 10.1016/j.cyto.2010.07.262 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 657NC UT WOS:000282418400238 ER PT J AU Waldmann, TA AF Waldmann, Thomas A. TI IL-15 for the treatment of metastatic malignant melanoma and metastatic renal cell cancer SO CYTOKINE LA English DT Meeting Abstract CT 8th Joint Conference of the International-Cytokine-Society/International-Society-for-and-Cytokine-Re search CY OCT 03-07, 2010 CL Chicago, IL SP Int Cytokine Soc, Int Soc Interferon & Cytokine Res C1 [Waldmann, Thomas A.] NCI, Metab Branch, CCR, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD OCT-NOV PY 2010 VL 52 IS 1-2 SI SI BP 68 EP 68 DI 10.1016/j.cyto.2010.07.287 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 657NC UT WOS:000282418400262 ER PT J AU Savan, R Reynolds, DA McFarland, AP Feigenbaum, L Ramakrishnan, K Shirota, H Klinman, DM Dunleavy, K Pittaluga, S Anderson, SK Donnelly, RP Wilson, WH Young, H AF Savan, Ram Reynolds, Della A. McFarland, Adelle P. Feigenbaum, Lionel Ramakrishnan, Karthika Shirota, Hidekazu Klinman, Dennis M. Dunleavy, Kieron Pittaluga, Stefania Anderson, Stephen K. Donnelly, Raymond P. Wilson, Wyndham H. Young, Howard TI A novel role of IL-22R1 as a possible driver of inflammation in ALK(+) anaplastic large cell lymphoma SO CYTOKINE LA English DT Meeting Abstract CT 8th Joint Conference of the International-Cytokine-Society/International-Society-for-and-Cytokine-Re search CY OCT 03-07, 2010 CL Chicago, IL SP Int Cytokine Soc, Int Soc Interferon & Cytokine Res C1 [Savan, Ram; Reynolds, Della A.; McFarland, Adelle P.; Ramakrishnan, Karthika; Shirota, Hidekazu; Klinman, Dennis M.; Anderson, Stephen K.; Young, Howard] NCI, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21702 USA. [Feigenbaum, Lionel] NCI, Lab Anim Sci Program, Ctr Canc Res, Frederick, MD 21702 USA. [Dunleavy, Kieron; Wilson, Wyndham H.] NCI, Metab Branch, Lymphoma Therapeut Sect, Ctr Canc Res, Bethesda, MD 20892 USA. [Pittaluga, Stefania] NCI, Pathol Lab, Hematopathol Sect, Ctr Canc Res, Bethesda, MD 20892 USA. [Donnelly, Raymond P.] US FDA, Div Therapeut Prot, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD OCT-NOV PY 2010 VL 52 IS 1-2 SI SI BP 69 EP 69 DI 10.1016/j.cyto.2010.07.291 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 657NC UT WOS:000282418400266 ER PT J AU Taylor, RT Lubick, KJ Best, SM AF Taylor, R. Travis Lubick, Kirk J. Best, Sonia M. TI TRIM79, A novel interferon stimulated gene, restricts flavivirus replication by degrading the viral RNA polymerase SO CYTOKINE LA English DT Meeting Abstract CT 8th Joint Conference of the International-Cytokine-Society/International-Society-for-and-Cytokine-Re search CY OCT 03-07, 2010 CL Chicago, IL SP Int Cytokine Soc, Int Soc Interferon & Cytokine Res C1 [Taylor, R. Travis; Lubick, Kirk J.; Best, Sonia M.] NIAID, Virol Lab, Rocky Mt Labs, DIR,NIH, Hamilton, MT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD OCT-NOV PY 2010 VL 52 IS 1-2 SI SI BP 70 EP 71 DI 10.1016/j.cyto.2010.07.297 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 657NC UT WOS:000282418400271 ER PT J AU Thomas, E Gonzalez, VD Modi, AA Noureddin, M Rotman, Y Liang, TJ AF Thomas, Emmanuel Gonzalez, Veronica D. Modi, Ankit A. Noureddin, Mazen Rotman, Yaron Liang, T. Jake TI Characterization of the interferon lambda (IL28/29) antiviral pathway in cell culture, human and chimpanzee models of HCV infection SO CYTOKINE LA English DT Meeting Abstract CT 8th Joint Conference of the International-Cytokine-Society/International-Society-for-and-Cytokine-Re search CY OCT 03-07, 2010 CL Chicago, IL SP Int Cytokine Soc, Int Soc Interferon & Cytokine Res C1 [Thomas, Emmanuel; Gonzalez, Veronica D.; Modi, Ankit A.; Noureddin, Mazen; Rotman, Yaron; Liang, T. Jake] NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD OCT-NOV PY 2010 VL 52 IS 1-2 SI SI BP 71 EP 71 DI 10.1016/j.cyto.2010.07.298 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 657NC UT WOS:000282418400272 ER PT J AU Tsuno, T Mejido, J Zhao, T Phillips, T Bekisz, J Zoon, KC AF Tsuno, Takaya Mejido, Josef Zhao, Togmao Phillips, Terry Bekisz, Joseph Zoon, Kathryn C. TI The anti-proliferative activity of IFN-alpha mediated by BID through TRAIL SO CYTOKINE LA English DT Meeting Abstract CT 8th Joint Conference of the International-Cytokine-Society/International-Society-for-and-Cytokine-Re search CY OCT 03-07, 2010 CL Chicago, IL SP Int Cytokine Soc, Int Soc Interferon & Cytokine Res C1 [Tsuno, Takaya; Mejido, Josef; Zhao, Togmao; Phillips, Terry; Bekisz, Joseph; Zoon, Kathryn C.] NIAID, Cytokine Biol Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD OCT-NOV PY 2010 VL 52 IS 1-2 SI SI BP 75 EP 75 DI 10.1016/j.cyto.2010.07.435 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 657NC UT WOS:000282418400285 ER PT J AU Hoshino, T Sakazaki, Y Kawayama, T Imaoka, H Kinoshita, T Sawada, M Oda, H Okamoto, M Young, HA Aizawa, H AF Hoshino, Tomoaki Sakazaki, Yuki Kawayama, Tomotaka Imaoka, Haruki Kinoshita, Takashi Sawada, Masanori Oda, Hanako Okamoto, Masaki Young, Howard A. Aizawa, Hisamichi TI Role of proinflammatory cytokines in respiratory diseases SO CYTOKINE LA English DT Meeting Abstract CT 8th Joint Conference of the International-Cytokine-Society/International-Society-for-and-Cytokine-Re search CY OCT 03-07, 2010 CL Chicago, IL SP Int Cytokine Soc, Int Soc Interferon & Cytokine Res C1 [Hoshino, Tomoaki; Sakazaki, Yuki; Kawayama, Tomotaka; Imaoka, Haruki; Kinoshita, Takashi; Sawada, Masanori; Oda, Hanako; Okamoto, Masaki; Aizawa, Hisamichi] Kurume Univ, Sch Med, Dept Internal Med, Kurume, Fukuoka 830, Japan. [Young, Howard A.] NCI, Canc & Inflammat Program, Expt Immunol Lab, Ctr Canc Res, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD OCT-NOV PY 2010 VL 52 IS 1-2 SI SI BP 76 EP 76 DI 10.1016/j.cyto.2010.07.316 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 657NC UT WOS:000282418400287 ER PT J AU Robertson, SJ Best, SM AF Robertson, Shelly J. Best, Sonja M. TI Tick-borne flavivirus infection of dendritic cells inhibits IL-12 production SO CYTOKINE LA English DT Meeting Abstract CT 8th Joint Conference of the International-Cytokine-Society/International-Society-for-and-Cytokine-Re search CY OCT 03-07, 2010 CL Chicago, IL SP Int Cytokine Soc, Int Soc Interferon & Cytokine Res C1 [Robertson, Shelly J.; Best, Sonja M.] NIAID, Virol Lab, Rocky Mt Labs, DIR,NIH, Hamilton, MT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD OCT-NOV PY 2010 VL 52 IS 1-2 SI SI BP 79 EP 79 DI 10.1016/j.cyto.2010.07.328 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 657NC UT WOS:000282418400298 ER PT J AU Bax, H Freeman, AF Hsu, AP Browne, SK Marciano, BE Paulson, M Fowler, C Ding, L Sampaio, EP Holland, SM AF Bax, H. Freeman, A. F. Hsu, A. P. Browne, S. K. Marciano, B. E. Paulson, M. Fowler, C. Ding, L. Sampaio, E. P. Holland, S. M. TI Therapeutic exploitation of shared IFN gamma and IFN alpha signaling for mycobacterial disease SO CYTOKINE LA English DT Meeting Abstract CT 8th Joint Conference of the International-Cytokine-Society/International-Society-for-and-Cytokine-Re search CY OCT 03-07, 2010 CL Chicago, IL SP Int Cytokine Soc, Int Soc Interferon & Cytokine Res C1 [Bax, H.; Freeman, A. F.; Hsu, A. P.; Browne, S. K.; Marciano, B. E.; Paulson, M.; Fowler, C.; Ding, L.; Sampaio, E. P.; Holland, S. M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD OCT-NOV PY 2010 VL 52 IS 1-2 SI SI BP 80 EP 80 DI 10.1016/j.cyto.2010.07.332 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 657NC UT WOS:000282418400301 ER PT J AU Cardone, M Mason, A Riboldi, E Stewart, CA Gerosa, F Trinchieri, G Lyakh, L AF Cardone, Marco Mason, Anna Riboldi, Elena Stewart, Charles A. Gerosa, Franca Trinchieri, Giorgio Lyakh, Lyudmila TI Role of IL-1 and TNF in human monocyte-derived dendritic cell responses following beta-glucan and LPS stimulation SO CYTOKINE LA English DT Meeting Abstract CT 8th Joint Conference of the International-Cytokine-Society/International-Society-for-and-Cytokine-Re search CY OCT 03-07, 2010 CL Chicago, IL SP Int Cytokine Soc, Int Soc Interferon & Cytokine Res C1 [Cardone, Marco; Mason, Anna; Riboldi, Elena; Stewart, Charles A.; Trinchieri, Giorgio; Lyakh, Lyudmila] NCI, Canc Immunobiol Sect, Expt Immunol Lab, Canc & Inflammat Program,CCR, Frederick, MD 21702 USA. [Gerosa, Franca] Univ Verona, Immunol Sect, Dept Pathol, Verona, Italy. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD OCT-NOV PY 2010 VL 52 IS 1-2 SI SI BP 83 EP 84 DI 10.1016/j.cyto.2010.07.347 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 657NC UT WOS:000282418400315 ER PT J AU Hong, CW Luckey, M Adams, AJ Park, JH AF Hong, Changwan Luckey, Megan Adams, Anthony J. Park, Jung-Hyun TI Active regulation of common gamma chain expression is critical for T cell development and homeostasis SO CYTOKINE LA English DT Meeting Abstract CT 8th Joint Conference of the International-Cytokine-Society/International-Society-for-and-Cytokine-Re search CY OCT 03-07, 2010 CL Chicago, IL SP Int Cytokine Soc, Int Soc Interferon & Cytokine Res C1 [Hong, Changwan; Luckey, Megan; Adams, Anthony J.; Park, Jung-Hyun] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RI Park, Jung Hyun /B-5712-2015; Davis, Megan/F-5339-2015 OI Park, Jung Hyun /0000-0002-9547-9055; NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD OCT-NOV PY 2010 VL 52 IS 1-2 SI SI BP 86 EP 86 DI 10.1016/j.cyto.2010.07.358 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 657NC UT WOS:000282418400325 ER PT J AU Wan, ECK Leonard, WJ AF Wan, Edwin C. K. Leonard, Warren J. TI IL-21 induces apoptosis of splenic conventional dendritic cells through STAT3 and BIM and can be rescued by GM-CSF SO CYTOKINE LA English DT Meeting Abstract CT 8th Joint Conference of the International-Cytokine-Society/International-Society-for-and-Cytokine-Re search CY OCT 03-07, 2010 CL Chicago, IL SP Int Cytokine Soc, Int Soc Interferon & Cytokine Res C1 [Wan, Edwin C. K.; Leonard, Warren J.] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD OCT-NOV PY 2010 VL 52 IS 1-2 SI SI BP 87 EP 87 DI 10.1016/j.cyto.2010.07.367 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 657NC UT WOS:000282418400333 ER PT J AU Murphy, AA Zhang, XZ Yang, J Donnelly, R Young, H Lempicki, RA Kottilil, S AF Murphy, Alison A. Zhang, Xiaozhen Yang, Jun Donnelly, Raymond Young, Howard Lempicki, Richard A. Kottilil, Shyam TI Differential transcriptosome profiles and antiviral effect of interferon-lambda and interferon-alpha on HCV-infected and uninfected hepatoma cells SO CYTOKINE LA English DT Meeting Abstract CT 8th Joint Conference of the International-Cytokine-Society/International-Society-for-and-Cytokine-Re search CY OCT 03-07, 2010 CL Chicago, IL SP Int Cytokine Soc, Int Soc Interferon & Cytokine Res C1 [Murphy, Alison A.; Zhang, Xiaozhen; Kottilil, Shyam] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. [Yang, Jun; Lempicki, Richard A.] SAIC Frederick, Frederick, MD USA. [Donnelly, Raymond] US FDA, CDER, Bethesda, MD 20014 USA. [Young, Howard] NCI, Expt Immunol Lab, Ctr Canc Res, Frederick, MD 21702 USA. RI Lempicki, Richard/E-1844-2012 OI Lempicki, Richard/0000-0002-7059-409X NR 0 TC 0 Z9 0 U1 0 U2 2 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD OCT-NOV PY 2010 VL 52 IS 1-2 SI SI BP 92 EP 92 DI 10.1016/j.cyto.2010.07.389 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 657NC UT WOS:000282418400353 ER PT J AU Tuleuova, N Ramankulov, E Revzin, A AF Tuleuova, Nazgul Ramankulov, Erlan Revzin, Alexander TI Micropatterning aptamer beacons on cell culture surfaces for detection of cytokine release SO CYTOKINE LA English DT Meeting Abstract CT 8th Joint Conference of the International-Cytokine-Society/International-Society-for-and-Cytokine-Re search CY OCT 03-07, 2010 CL Chicago, IL SP Int Cytokine Soc, Int Soc Interferon & Cytokine Res C1 [Tuleuova, Nazgul; Revzin, Alexander] Univ Calif Davis, Dept Biomed Engn, Davis, CA 95616 USA. [Tuleuova, Nazgul; Ramankulov, Erlan] Natl Biotechnol Ctr, Astana, Kazakhstan. RI Ramanculov, Erlan/E-2823-2013 NR 0 TC 1 Z9 1 U1 1 U2 12 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD OCT-NOV PY 2010 VL 52 IS 1-2 SI SI BP 97 EP 97 DI 10.1016/j.cyto.2010.07.414 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 657NC UT WOS:000282418400378 ER PT J AU Bergamaschi, C Ganneru, B Rosati, M Usami, O Valentin, A Beach, RK Alicea, C Felber, BK Pavlakis, GN AF Bergamaschi, Cristina Ganneru, Brunda Rosati, Margherita Usami, Osamu Valentin, Antonio Beach, Rachel K. Alicea, Candido Felber, Barbara K. Pavlakis, George N. TI Heterodimeric IL-15/IL-15R alpha accelerates immune reconstitution in lymphopenic mice SO CYTOKINE LA English DT Meeting Abstract CT 8th Joint Conference of the International-Cytokine-Society/International-Society-for-and-Cytokine-Re search CY OCT 03-07, 2010 CL Chicago, IL SP Int Cytokine Soc, Int Soc Interferon & Cytokine Res C1 [Alicea, Candido; Felber, Barbara K.] NCI, Human Retrovirus Pathogenesis Sect, Vaccine Branch, Ctr Canc Res, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD OCT-NOV PY 2010 VL 52 IS 1-2 SI SI BP 100 EP 100 DI 10.1016/j.cyto.2010.07.424 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 657NC UT WOS:000282418400386 ER PT J AU Sereti, I AF Sereti, Irini TI Cytokine-based therapies in HIV infection: Lessons from IL-2 and expectations from IL-7 SO CYTOKINE LA English DT Meeting Abstract CT 8th Joint Conference of the International-Cytokine-Society/International-Society-for-and-Cytokine-Re search CY OCT 03-07, 2010 CL Chicago, IL SP Int Cytokine Soc, Int Soc Interferon & Cytokine Res C1 [Sereti, Irini] NIH, Dept Infect Dis, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD OCT-NOV PY 2010 VL 52 IS 1-2 SI SI BP 100 EP 100 DI 10.1016/j.cyto.2010.07.422 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 657NC UT WOS:000282418400385 ER PT J AU Zdanov, A AF Zdanov, Alexander TI Structural analysis of cytokines comprising the IL-10 family SO CYTOKINE & GROWTH FACTOR REVIEWS LA English DT Review DE Class II cytokines; Interleukin-10; Ligand/receptor interactions; Helix bundle; Signal transduction ID DIFFERENTIATION-ASSOCIATED GENE; I INTERFERON FAMILY; VIRUS PROTEIN BCRF1; X-RAY-DIFFRACTION; CRYSTAL-STRUCTURE; INTERLEUKIN-10 FAMILY; RECEPTOR COMPLEXES; MELANOMA DIFFERENTIATION; HELICAL CYTOKINES; INDUCIBLE FACTOR AB Interleukin-10 (IL-10) family of cytokines includes a number of its viral homologs and eight cellular cytokines (IL-19, IL-20, IL-22, IL-24, IL-26, IL-28A, IL-28B, and IL-29). The latter three proteins are also known as IFN-lambda 2, IFN-lambda 3, and IFN-lambda 1, and are recognized as type III (or lambda) interferons. Most of the cellular homologs of IL-10 are monomeric in solution, whereas IL-10 and its viral homologs are intercalated dimers consisting of two helical bundle domains topologically similar to the monomeric members of the family. A classical four-helix bundle, a signature element of all helical cytokines, is always found as part of the domain of each member of the IL-10 family. The only crystal structures of these cytokine receptors that have been determined to date are for their extracellular domains (ECDs). Each ECD consists of two beta-sandwich domains connected in the middle by a linkage. Signal transduction occurs when a cytokine binds to its two appropriate receptor chains. IL-10 and its viral homologs use the same IL-10 receptor system, whereas the cellular homologs of IL-10 use their own receptors, which in some cases may overlap and be used in different pairwise combinations. The known structures of binary complexes allowed for marking of the receptor binding site, which always includes helix A, loop AB and helix F (IL-10 notations) on the side of a ligand, loops of the N-terminal and C-terminal domains directed toward the ligand, and the interdomain linkage of the ECD. An analysis of the published structures of both the binary and ternary complexes of all helical cytokines allowed for the generation of a model of the signaling complex of IL-10. The receptor binding site I of the high affinity receptor IL-10R1 is exactly the same as in the crystal structure of the binary IL-10/sIL-10R1 complex, whereas the receptor binding site 11 is located on the surface of the first and the third helices of the four-helix bundle. The receptor/receptor interface, or site III, is formed between the C-terminal domains of IL-10R1 and IL-10R2. Published by Elsevier Ltd. C1 [Zdanov, Alexander] NCI, Macromol Crystallog Lab, Ctr Canc Res, Frederick, MD 21702 USA. EM wlodawer@nih.gov FU NIH, National Cancer Institute, Center for Cancer Research FX This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. Special thanks go to Dr. Alexander Wlodawer for accurately proofreading the manuscript. NR 96 TC 27 Z9 31 U1 1 U2 11 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1359-6101 J9 CYTOKINE GROWTH F R JI Cytokine Growth Factor Rev. PD OCT PY 2010 VL 21 IS 5 SI SI BP 325 EP 330 DI 10.1016/j.cytogfr.2010.08.003 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 705IU UT WOS:000286122900002 PM 20846897 ER PT J AU Donnelly, RP Sheikh, F Dickensheets, H Savan, R Young, HA Walter, MR AF Donnelly, Raymond P. Sheikh, Faruk Dickensheets, Harold Savan, Ram Young, Howard A. Walter, Mark R. TI Interleukin-26: An IL-10-related cytokine produced by Th17 cells SO CYTOKINE & GROWTH FACTOR REVIEWS LA English DT Review DE IL-26; Th17 cells; IL-20R1; STAT3; Inflammation ID HUMAN IL-10 RECEPTOR; CRYSTAL-STRUCTURE; INTERFERON-GAMMA; CUTTING EDGE; SEQUENCE ALIGNMENT; COMMON CHAIN; IL-22; EXPRESSION; COMPLEX; IDENTIFICATION AB IL-26 is classified as a member of the IL-10 cytokine family because it has limited sequence homology to IL-10 and the IL-10-related cytokines. The human IL-26 gene, IL26, is located on chromosome 12q15 between the genes for two other important class-2 cytokines, IFNG (IFN-gamma) and IL22 (IL-22). IL-26 is often co-expressed with IL-22 by activated T cells, especially Th17 cells. It signals through a heterodimeric receptor complex composed of the IL-20R1 and IL-10R2 chains. I1-26 receptors are primarily expressed on non-hematopoietic cell types, particularly epithelial cells. Signaling through IL-26 receptor complexes results in the activation of STAT1 and STAT3 with subsequent induction of IL-26-responsive genes. The biological functions of IL-26 have only begun to be defined. Published by Elsevier Ltd. C1 [Donnelly, Raymond P.; Sheikh, Faruk; Dickensheets, Harold] US FDA, Div Therapeut Prot, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. [Savan, Ram; Young, Howard A.] NCI, Expt Immunol Lab, Canc & Inflammat Program, NIH, Frederick, MD 21702 USA. [Walter, Mark R.] Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA. RP Donnelly, RP (reprint author), US FDA, Div Therapeut Prot, Ctr Drug Evaluat & Res, Bldg 29A,Room 3B15,29 Lincoln Dr, Bethesda, MD 20892 USA. EM Raymond.Donnelly@fda.hhs.gov FU National Institutes of Health (NIH) [AI47300, AI47300-08S]; National Cancer Institute (NCI) FX This work was supported in part by U.S. Public Health Service Grants AI47300 and AI47300-08S from the National Institutes of Health (NIH) to M.R.W and by the Intramural Research Program of the National Cancer Institute (NCI). NR 53 TC 33 Z9 35 U1 3 U2 15 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1359-6101 J9 CYTOKINE GROWTH F R JI Cytokine Growth Factor Rev. PD OCT PY 2010 VL 21 IS 5 SI SI BP 393 EP 401 DI 10.1016/j.cytogfr.2010.09.001 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 705IU UT WOS:000286122900008 PM 20947410 ER PT J AU Clark, AJ Romero, R Petty, HR AF Clark, Andrea J. Romero, Roberto Petty, Howard R. TI Improved Detection of Nicotinamide Adenine Dinucleotide Phosphate Oscillations Within Human Neutrophils SO CYTOMETRY PART A LA English DT Article DE microfluorometry; autofluorescence; cell shape; metabolism ID FLUORESCENCE MICROSCOPY; YEAST-CELLS; NAD(P)H AB Kinetic studies of nicotinamide adenine dinucleotide phosphate autofluorescence have been conducted in adherent neutrophils using an improved microscopic photometry system incorporating low noise excitation and detection systems. Dynamic autofluorescence oscillations were found with periods ranging from similar to 4 min to similar to 10 s. The largest portion of the population of oscillating neutrophils (32%) had periods near 2 min. The next largest group at 25% exhibited periods of 1 min or less. These oscillations could not be accounted for by instrument artifacts, cell shape changes away from the focal plane, or other factors. They disappeared when detergent was added to oscillating cells. Higher-frequency oscillations disappeared as cells changed shape, indicating a correlation between these two processes. This approach provides a reliable method to monitor this cellular property. (C) 2010 International Society for Advancement of Cytometry C1 [Clark, Andrea J.; Petty, Howard R.] Univ Michigan, Dept Ophthalmol & Visual Sci, Sch Med, Ann Arbor, MI 48105 USA. [Romero, Roberto] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, Div Intramural Res, NIH, Bethesda, MD USA. [Romero, Roberto] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol Res Branch, Div Intramural Res, NIH, Detroit, MI USA. [Romero, Roberto] Wayne State Univ, Ctr Mol Med & Genet, Detroit, MI USA. [Romero, Roberto] Detroit Med Ctr, Hutzel Womens Hosp, Detroit, MI USA. [Petty, Howard R.] Univ Michigan, Sch Med, Dept Microbiol & Immunol, Ann Arbor, MI 48109 USA. RP Petty, HR (reprint author), Univ Michigan, Dept Ophthalmol & Visual Sci, Sch Med, 1000 Wall St, Ann Arbor, MI 48105 USA. EM hpetty@umich.edu FU Division of Intramural Research of the Eunice Kennedy Schriver National Institute of Child Health and Human Development, NIH, DHHS [N01-HD-2-3342, WSU04055] FX Grant sponsor: Division of Intramural Research of the Eunice Kennedy Schriver National Institute of Child Health and Human Development, NIH, DHHS; Grant numbers: contract N01-HD-2-3342 and subcontract WSU04055. NR 16 TC 0 Z9 0 U1 1 U2 2 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 OCT PY 2010 VL 77A IS 10 BP 976 EP 982 DI 10.1002/cyto.a.20961 PG 7 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 664ZV UT WOS:000283003900011 PM 21290472 ER PT J AU Adams, DK Flierl, GR AF Adams, Diane K. Flierl, Glenn R. TI Modeled interactions of mesoscale eddies with the East Pacific Rise: Implications for larval dispersal SO DEEP-SEA RESEARCH PART I-OCEANOGRAPHIC RESEARCH PAPERS LA English DT Article DE Vortex dynamics; Mesoscale eddies; Hydrothermal vents; Larval dispersal; Ridge topography ID BAROTROPIC ROSSBY WAVES; SEA HYDROTHERMAL VENTS; TROPICAL PACIFIC; AGULHAS RINGS; OCEAN; EDDY; EVOLUTION; RIDGE; VARIABILITY; TOPOGRAPHY AB Larval transport from distant populations is essential for maintenance and renewal of populations in patchy and disturbed ecosystems such as deep-sea hydrothermal vents. We use quasi-geostrophic modeling to consider the potential for long-distance dispersal of hydrothermal vent larvae in mesoscale eddies interacting with the northern East Pacific Rise. Modeled eddy dynamics were similar to the observed propagation dynamics of Tehuantepec eddies, including their ability to cross the ridge. Simulated surface anticyclones were associated with coherent cyclones in the deep layer with relatively strong current velocities that could significantly increase the dispersal potential of passive particles. Eddy interactions with ridge topography further enhanced tracer dispersal along the ridge axis through shearing and elongation of the eddy core. Simulations suggest that the passage of an eddy would result in local loss from the vent field and aggregate transport with potential enhancement of dispersal between vent fields separated by up to 270 km. Based on the latitude at which most Tehuantepec eddies cross the ridge, eddy-induced flows would enhance connectivity between the 13 degrees N, 11 degrees N, and 9 degrees N vent fields along the East Pacific Rise asymmetrically with higher transport from northern vent fields to southern vent fields. Published by Elsevier Ltd. C1 [Adams, Diane K.] Woods Hole Oceanog Inst, Woods Hole, MA 02543 USA. [Flierl, Glenn R.] MIT, Cambridge, MA 02139 USA. RP Adams, DK (reprint author), Natl Inst Dent & Craniofacial Res, NIH, 30 Convent Dr, Bethesda, MD 20892 USA. EM dadams@whoi.edu; glenn@lake.mit.edu RI Adams, Diane/E-7831-2015 OI Adams, Diane/0000-0001-6638-5781 FU National Science Foundation [OCE-0424953]; National Defense Science and Engineering Graduate fellowship FX We are grateful to Lauren Mullineaux, Susan Mills, Carly Strasser, Stace Beaulieu, Irene Garcia-Berdeal, Jesus Pineda, and Tim Shank for discussions at various stages of research and manuscript preparation. M.I.T.'s Project Athena provided computational resources. Comments from four anonymous reviewers improved the manuscript. Funding was provided by National Science Foundation Grant OCE-0424953 to L.S. Mullineaux and a National Defense Science and Engineering Graduate fellowship to D.K.A. NR 64 TC 10 Z9 10 U1 0 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0967-0637 EI 1879-0119 J9 DEEP-SEA RES PT I JI Deep-Sea Res. Part I-Oceanogr. Res. Pap. PD OCT PY 2010 VL 57 IS 10 BP 1163 EP 1176 DI 10.1016/j.dsr.2010.06.009 PG 14 WC Oceanography SC Oceanography GA 667PR UT WOS:000283206600002 ER PT J AU Molloy, CA Kalkwarf, HJ Manning-Courtney, P Mills, JL Hediger, ML AF Molloy, Cynthia A. Kalkwarf, Heidi J. Manning-Courtney, Patricia Mills, James L. Hediger, Mary L. TI Plasma 25(OH)D concentration in children with autism spectrum disorder SO DEVELOPMENTAL MEDICINE AND CHILD NEUROLOGY LA English DT Letter ID VITAMIN-D; ADOLESCENTS; EPILEPSY C1 [Molloy, Cynthia A.] Univ Cincinnati, Med Ctr, Coll Med, Cincinnati Childrens Hosp,Div Neurol,Dept Pediat, Cincinnati, OH 45267 USA. [Molloy, Cynthia A.] Univ Cincinnati, Coll Med, Div Dev & Behav Pediat DDBP, Cincinnati, OH 45267 USA. [Kalkwarf, Heidi J.] Univ Cincinnati, Med Ctr, Coll Med,Div Gen & Community Pediat, Cincinnati Childrens Hosp,Dept Pediat, Cincinnati, OH 45267 USA. [Manning-Courtney, Patricia] Cincinnati Childrens Hosp, Med Ctr, DDBP, Kelly OLeary Ctr Autism Spectrum Disorders, Cincinnati, OH USA. [Mills, James L.; Hediger, Mary L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD USA. RP Molloy, CA (reprint author), Univ Cincinnati, Med Ctr, Coll Med, Cincinnati Childrens Hosp,Div Neurol,Dept Pediat, Cincinnati, OH 45267 USA. EM cynthia.molloy@cchmc.org FU NCATS NIH HHS [UL1 TR000077]; NCRR NIH HHS [M01 RR008084, M01 RR08084]; NICHD NIH HHS [Z01 HD008742] NR 12 TC 18 Z9 19 U1 1 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0012-1622 J9 DEV MED CHILD NEUROL JI Dev. Med. Child Neurol. PD OCT PY 2010 VL 52 IS 10 BP 969 EP 971 DI 10.1111/j.1469-8749.2010.03704.x PG 3 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 647TI UT WOS:000281641800025 PM 20497452 ER PT J AU Sosenko, JM Skyler, JS Krischer, JP Greenbaum, CJ Mahon, J Rafkin, LE Cuthbertson, D Cowie, C Herold, K Eisenbarth, G Palmer, JP AF Sosenko, Jay M. Skyler, Jay S. Krischer, Jeffrey P. Greenbaum, Carla J. Mahon, Jeffrey Rafkin, Lisa E. Cuthbertson, David Cowie, Catherine Herold, Kevan Eisenbarth, George Palmer, Jerry P. CA Diabet Prevention Trial Type 1 TI Glucose Excursions Between States of Glycemia With Progression to Type 1 Diabetes in the Diabetes Prevention Trial-Type 1 (DPT-1) SO DIABETES LA English DT Article ID INSULIN-RESISTANCE; PARTICIPANTS AB OBJECTIVE We characterized fluctuations between states of glycemia in progressors to type 1 diabetes and studied whether those fluctuations are related to the early C-peptide response to oral glucose. RESEARCH DESIGN AND METHODS Oral glucose tolerance tests (OGTTs) from differing states of glycemia were compared within individuals for glucose and C-peptide. Dysglycemic OGTTs (DYSOGTTs) were compared with normal OGTTs (NLOGTT), while transient diabetic OGTTs (TDOGTTs) were compared with subsequent nondiabetic OGTTs and with OGTTs performed at diagnosis. RESULTS Of 135 progressors with four or more OGTTs, 30 (22%) went from NLOGTTs to DYSOGTTs at least twice. Area under the curve (AUC) glucose values from the second NLOGTT were higher (P < 0.001) than values from the first NLOGTr. Among 98 progressors whose DYSOGTTs and NLOGTTs were synchronized for the time before diagnosis, despite higher glucose levels (P < 0.01 at all time points) in the DYSOGTTs, 30- to 0-min C-peptide difference values changed little. Likewise, 30- to 0-min C-peptide difference values did not differ between TDOGTTs and subsequent (within 3 months) nondiabetic OGTTs in 55 progressors. In contrast, as glucose levels increased overall from the first to last OGTTs before diagnosis (P < 0.001 at every time point, n = 207), 30- to 0-min C-peptide difference values decreased (P < 0.001). CONCLUSIONS Glucose levels fluctuate widely as they gradually increase overall with progression to type 1 diabetes. As glucose levels increase, the early C-peptide response declines. In contrast, glucose fluctuations are not related to the early C-peptide response. This suggests that changes in insulin sensitivity underlie the glucose fluctuations. Diabetes 59:2386-2389, 2010 C1 [Sosenko, Jay M.; Skyler, Jay S.; Rafkin, Lisa E.] Univ Miami, Div Endocrinol, Miami, FL 33152 USA. [Krischer, Jeffrey P.] Univ S Florida, Div Informat & Biostat, Tampa, FL USA. [Greenbaum, Carla J.] Benaroya Res Inst Virginia Mason, Seattle, WA USA. [Mahon, Jeffrey] Univ Western Ontario, Dept Epidemiol & Biostat, London, ON N6A 3K7, Canada. [Cuthbertson, David] Univ S Florida, Pediat Epidemiol Ctr, Tampa, FL USA. [Cowie, Catherine] NIDDKD, NIH, Bethesda, MD 20892 USA. [Herold, Kevan] Yale Univ, Sch Med, New Haven, CT USA. [Eisenbarth, George] Univ Colorado, HLA DNA Lab, Aurora, CO USA. [Palmer, Jerry P.] Univ Washington, Vet Adm Puget Sound Hlth Care Syst, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. RP Sosenko, JM (reprint author), Univ Miami, Div Endocrinol, Miami, FL 33152 USA. EM jsosenko@med.miami.edu RI Skyler, Jay/F-4211-2016 FU National Institutes of Health through the National Institute of Diabetes and Digestive and Kidney Diseases; National Institutes of Health through the National Institute of Allergy and Infectious Diseases; National Institutes of Health through the National Institute of Child Health and Human Development; General Clinical Research Centers Program; Juvenile Diabetes Research Foundation International; American Diabetes Association FX This work was funded by the National Institutes of Health through the National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Allergy and Infectious Diseases, National Institute of Child Health and Human Development, and General Clinical Research Centers Program; the Juvenile Diabetes Research Foundation International; and the American Diabetes Association. NR 15 TC 20 Z9 20 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD OCT PY 2010 VL 59 IS 10 BP 2386 EP 2389 DI 10.2337/db10-0534 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 667PJ UT WOS:000283205700010 PM 20682683 ER PT J AU Zhao, AZ Ohara-Imaizumi, M Brissova, M Benninger, RKP Xu, YW Hao, YH Abramowitz, J Boulay, G Powers, AC Piston, D Jiang, MS Nagamatsu, S Birnbaumer, L Gu, GQ AF Zhao, Aizhen Ohara-Imaizumi, Mica Brissova, Marcella Benninger, Richard K. P. Xu, Yanwen Hao, Yuhan Abramowitz, Joel Boulay, Guylain Powers, Alvin C. Piston, David Jiang, Meisheng Nagamatsu, Shinya Birnbaumer, Lutz Gu, Guoqiang TI G alpha o Represses Insulin Secretion by Reducing Vesicular Docking in Pancreatic beta-Cells SO DIABETES LA English DT Article ID ISLET-ACTIVATING PROTEIN; B-CELLS; SOMATOSTATIN INHIBITION; PRESYNAPTIC INHIBITION; GRANULE EXOCYTOSIS; MEMBRANE-PROTEIN; ADP-RIBOSYLATION; GAMMA-DIMERS; MOUSE; MECHANISMS AB OBJECTIVE Pertussis toxin uncoupling-based studies have shown that Gal and G alpha o can inhibit insulin secretion in pancreatic beta-cells. Yet it is unclear whether G alpha i and G alpha o operate through identical mechanisms and how these G-protein-mediated signals inhibit insulin secretion in vivo. Our objective is to examine whether/how G alpha o regulates islet development and insulin secretion in beta-cells. RESEARCH DESIGN AND METHODS Immunoassays were used to analyze the G alpha o expression in mouse pancreatic cells. G alpha o was specifically inactivated in pancreatic progenitor cells by pancreatic cell-specific gene deletion. Hormone expression and insulin secretion in response to different stimuli were assayed in vivo and in vitro. Electron microscope and total internal reflection fluorescence-based assays were used to evaluate how G alpha o regulates insulin vesicle docking and secretion in response to glucose stimulation. RESULTS Islet cells differentiate properly in G alpha o(-/-) mutant mice. G alpha o inactivation significantly enhances insulin secretion both in vivo and in isolation. G alpha o nullizygous beta-cells contain an increased number of insulin granules docked on the cell plasma membrane, although the total number of vesicles per beta-cell remains unchanged. CONCLUSIONS-G alpha o is not required for endocrine islet cell differentiation, but it regulates the number of insulin vesicles docked on the beta-cell membrane. Diabetes 59:2522-2529, 2010 C1 [Zhao, Aizhen; Xu, Yanwen; Hao, Yuhan; Gu, Guoqiang] Vanderbilt Univ, Med Ctr, Program Dev Biol, Nashville, TN 37203 USA. [Zhao, Aizhen; Xu, Yanwen; Hao, Yuhan; Gu, Guoqiang] Vanderbilt Univ, Med Ctr, Dept Cell & Dev Biol, Nashville, TN USA. [Ohara-Imaizumi, Mica; Nagamatsu, Shinya] Kyorin Univ, Sch Med Mitaka, Dept Biochem, Tokyo, Japan. [Brissova, Marcella; Benninger, Richard K. P.; Powers, Alvin C.; Piston, David] Vanderbilt Univ, Med Ctr, Dept Mol Physiol & Biophys, Nashville, TN USA. [Brissova, Marcella; Powers, Alvin C.] Vanderbilt Univ, Med Ctr, Dept Med, Div Endocrinol Diabet & Metab, Nashville, TN USA. [Brissova, Marcella; Powers, Alvin C.] VA Tennessee Valley Healthcare Syst, Nashville, TN USA. [Abramowitz, Joel; Birnbaumer, Lutz] Natl Inst Environm Hlth Sci, Transmembrane Signaling Grp, Neurobiol Lab, NIH,Dept Hlth & Human Serv, Res Triangle Pk, NC USA. [Boulay, Guylain] Univ Sherbrooke, Sch Med, Dept Pharmacol, Sherbrooke, PQ J1H 5N4, Canada. [Jiang, Meisheng] Univ Calif Los Angeles, Dept Mol & Med Pharmacol, Los Angeles, CA USA. RP Gu, GQ (reprint author), Vanderbilt Univ, Med Ctr, Program Dev Biol, Nashville, TN 37203 USA. EM guoqiang.gu@vanderbilt.edu RI Abramowitz, Joel/A-2620-2015; OI benninger, richard/0000-0002-5063-6096 FU National Institutes of Health [DK-069771, DK-53434, Z01-ES-101643, DK-66636, DK-69603, DK-63439]; JDRF [2009-371]; VA Research Service; Vanderbilt Mouse Metabolic Phenotyping Center [DK-59637]; Vanderbilt Diabetes Research and Training Center [DK-20593]; KAKENHI [C-20570189, 21113523, B-20390260]; Sumitomo Foundation; Research Foundation for Opto-Science and Technology FX This research was supported by grants from the National Institutes of Health (DK-069771 to M.J., DK-53434 to D.P.), JDRF (2009-371 to G.G.), and by the Intramural Research Program of the National Institutes of Health (Z01-ES-101643 to L.B.). A.C.P. was supported by grants from the JDRF, the VA Research Service, the National Institutes of Health (DK-66636, DK-69603, and DK-63439), the Vanderbilt Mouse Metabolic Phenotyping Center (DK-59637), and the Vanderbilt Diabetes Research and Training Center (DK-20593). S.N. was supported by the following resource: KAKENHI (C-20570189, 21113523 to M.O.-I., B-20390260 to S.N.), Sumitomo Foundation (to Astellas Foundation for Research on Metabolic Disorders (M.O.-I.), and Research Foundation for Opto-Science and Technology (M.O.-I.). TEM was performed in the Vanderbilt EM core facility, with help from Denny Kerns, Matt Stephenson, and Mary Dawes. The color print fee cost was covered by JDRF. NR 48 TC 11 Z9 11 U1 0 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD OCT PY 2010 VL 59 IS 10 BP 2522 EP 2529 DI 10.2337/db09-1719 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 667PJ UT WOS:000283205700025 PM 20622165 ER PT J AU Jablonski, KA McAteer, JB de Bakker, PIW Franks, PW Pollin, TI Hanson, RL Saxena, R Fowler, S Shuldiner, AR Knowler, WC Altshuler, D Florez, JC AF Jablonski, Kathleen A. McAteer, Jarred B. de Bakker, Paul I. W. Franks, Paul W. Pollin, Toni I. Hanson, Robert L. Saxena, Richa Fowler, Sarah Shuldiner, Alan R. Knowler, William C. Altshuler, David Florez, Jose C. CA Diabet Prevention Program Res Grp TI Common Variants in 40 Genes Assessed for Diabetes Incidence and Response to Metformin and Lifestyle Intervention in the Diabetes Prevention Program SO DIABETES LA English DT Article ID WIDE ASSOCIATION SCAN; CATION TRANSPORTER 1; ADMIXTURE MAP; LOCI; DISEASE; REQUIREMENT; DISCOVERY; MELLITUS AB OBJECTIVE-Genome-wide association studies have begun to elucidate the genetic architecture of type 2 diabetes. We examined whether single nucleotide polymorphisms (SNPs) identified through targeted complementary approaches affect diabetes incidence in the at-risk population of the Diabetes Prevention Program (DPP) and whether they influence a response to preventive interventions. RESEARCH DESIGN AND METHODS-We selected SNPs identified by prior genome-wide association studies for type 2 diabetes and related traits, or capturing common variation in 40 candidate genes previously associated with type 2 diabetes, implicated in monogenic diabetes, encoding type 2 diabetes drug targets or drug-metabolizing/transporting enzymes, or involved in relevant physiological processes. We analyzed 1,590 SNPs for association with incident diabetes and their interaction with response to metformin or lifestyle interventions in 2,994 DPP participants. We controlled for multiple hypothesis testing by assessing false discovery rates. RESULTS-We replicated the association of variants in the metformin transporter gene SLC47A1 with metformin response and detected nominal interactions in the AMP kinase (AMPK) gene STK11, the AMPK subunit genes PRKAA1 and PRK4.A2, and a missense SNP in SLC22A1, which encodes another metformin transporter. The most significant association with diabetes incidence occurred in the AMPK subunit gene PRKAG2 (hazard ratio 1.24, 95% CI 1.09-1.40, P = 7 x 10(-4)). Overall, there were nominal associations with diabetes incidence at 85 SNPs and nominal interactions with the metformin and lifestyle interventions at 91 and 69 mostly nonoverlapping SNPs, respectively. The lowest P values were consistent with experiment-wide 33% false discovery rates. CONCLUSIONS-We have identified potential genetic determinants of metformin response. These results merit confirmation in independent samples. Diabetes 59:2672-2681, 2010 C1 [McAteer, Jarred B.; Saxena, Richa; Altshuler, David; Florez, Jose C.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Jablonski, Kathleen A.; Fowler, Sarah] George Washington Univ, Ctr Biostat, Rockville, MD USA. [McAteer, Jarred B.; de Bakker, Paul I. W.; Saxena, Richa; Altshuler, David; Florez, Jose C.] Broad Inst, Prograrn Med & Populat Genet, Cambridge, MA USA. [de Bakker, Paul I. W.; Altshuler, David; Florez, Jose C.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [de Bakker, Paul I. W.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Franks, Paul W.] Umea Univ Hosp, Genet Epidemiol & Clin Res Grp, Dept Publ Hlth & Clin Med, Div Med, S-90185 Umea, Sweden. [Franks, Paul W.] Lund Univ, Dept Clin Sci, Malmo, Sweden. [Pollin, Toni I.; Shuldiner, Alan R.] Univ Maryland, Sch Med, Dept Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA. [Hanson, Robert L.; Knowler, William C.] Natl Inst Diabet & Digest & Kidney Dis, Diabet Epidemiol & Clin Res Sect, Phoenix, AZ USA. [Shuldiner, Alan R.] Vet Adm Med Ctr, Geriatr Res & Educ Clin Ctr, Baltimore, MD 21218 USA. [Altshuler, David] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. [Altshuler, David; Florez, Jose C.] Massachusetts Gen Hosp, Diabet Res Ctr, Diabet Unit, Dept Med, Boston, MA 02114 USA. RP Florez, JC (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. EM dppmail@biostat.bsc.gwu.edu RI Altshuler, David/A-4476-2009; de Bakker, Paul/B-8730-2009; Hanson, Robert/O-3238-2015; OI Altshuler, David/0000-0002-7250-4107; de Bakker, Paul/0000-0001-7735-7858; Hanson, Robert/0000-0002-4252-7068; Franks, Paul/0000-0002-0520-7604 FU Doris Duke Charitable Foundation; Novo Nordisk; Swedish Heart-Lung Foundation; Swedish Diabetes Association; Pahlssons Foundation; Swedish Research Council; Umea University; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health; NIDDK; Indian Health Service; Office of Research on Minority Health; National Institute of Child Health and Human Development; National Institute on Aging; Office of Research on Women's Health; Centers for Disease Control and Prevention; American Diabetes Association; [R01 DK072041] FX The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health provided funding to the clinical centers and the coordinating center for the design and conduct of the study and collection, management, analysis, and interpretation of the data. The Southwestern American Indian Centers were supported directly by the NIDDK and the Indian Health Service. The General Clinical Research Center Program, National Center for Research Resources, and the Department of Veterans Affairs supported data collection at many of the clinical centers. Funding for data collection and participant support was also provided by the Office of Research on Minority Health, the National Institute of Child Health and Human Development, the National Institute on Aging, the Office of Research on Women's Health, the Centers for Disease Control and Prevention, and the American Diabetes Association. Bristol-Myers Squibb and Parke-Davis provided medication. This research was also supported in part by the intramural research program of the NIDDK. Life Scan, Health O Meter, Hoechst Marion Roussel, Merck-Medco Managed Care, Merck and Company, Nike Sports Marketing, Slim Fast Foods, and Quaker Oats donated materials, equipment, or medicines for concomitant conditions. McKesson BioServices, Matthews Media Group, and the Henry M. Jackson Foundation provided support services under subcontract with the coordinating center. A complete list of centers, investigators, and staff can be found in the online appendix.; This work was funded by R01 DK072041 to K.A.J., T.I.P., A.R.S., D.A., and J.C.F. J.C.F. is also supported by the Massachusetts General Hospital and a Clinical Scientist Development Award by the Doris Duke Charitable Foundation. This work was partially supported by a Doris Duke Charitable Foundation Distinguished Scientist Clinical Award to D.A. P.W.F. was supported in part by grants from Novo Nordisk, the Swedish Heart-Lung Foundation, the Swedish Diabetes Association, Pahlssons Foundation, the Swedish Research Council, and a Career Development Award from Umea University. J.C.F. received consulting honoraria from Publicis Healthcare, Merck, bioStrategies, XOMA, and Daiichi-Sankyo and has been a paid invited speaker at internal scientific seminars hosted by Pfizer and Alnylam Pharmaceuticals. NR 35 TC 106 Z9 111 U1 0 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD OCT PY 2010 VL 59 IS 10 BP 2672 EP 2681 DI 10.2337/db10-0543 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 667PJ UT WOS:000283205700042 PM 20682687 ER PT J AU Mann, DM Carson, AP Shimbo, D Fonseca, V Fox, CS Muntner, P AF Mann, Devin M. Carson, April P. Shimbo, Daichi Fonseca, Vivian Fox, Caroline S. Muntner, Paul TI Impact of A1C Screening Criterion on the Diagnosis of Pre-Diabetes Among U.S. Adults SO DIABETES CARE LA English DT Article ID IMPAIRED FASTING GLUCOSE; NUTRITION EXAMINATION SURVEY; DIABETES-MELLITUS; NATIONAL-HEALTH; RISK; US; POPULATION; PREVENTION; TOLERANCE; DISEASE AB OBJECTIVE - New clinical practice recommendations include A C as an alternative to fasting glucose as a diagnostic test for identifying pre-diabetes. The impact of these new recommendations on the diagnosis of pre-diabetes is unknown. RESEARCH DESIGN AND METHODS Data from the National Health and Nutrition Examination Survey 1999-2006 (n=7,029) were analyzed to determine the percentage and number of U.S. adults without diabetes classified as having pre-diabetes by the elevated A1C (5.7-6.4%) and by the impaired fasting glucose (IFG) (fasting glucose 100-125 mg/dl) criterion separately. Test characteristics (sensitivity, specificity, and positive and negative predictive values) using IFG as the reference standard were calculated. RESULTS The prevalence of pre-diabetes among U.S. adults was 12.6% by the A1C criterion and 28.2% by the fasting glucose criterion. Only 7.7, of U.S. adults, reflecting 61 and 27% of those with pre-diabetes by A1C and fasting glucose, respeciively, had pre-diabetes according to both definitions. A1C used alone would reclassify 37.6 million Americans with LEG to not having pre-diabetes and 8.9 million without IFG to having pre-diabetes (46.5 million reclassified). Using IFG as the reference standard, pre-diabetes by the A1C criterion has 27% sensitivity, 93% specificity, 61% positive predictive value, and 77% negative predictive value. CONCLUSIONS - Using A1C as the pre-diabetes criterion would reclassify the prediabetes diagnosis of nearly 50 million Americans. It is imperative that clinicians and health systems understand the differences and similarities in using A1C or IFG in diagnosis of pre-diabetes. C1 [Mann, Devin M.] Mt Sinai Sch Med, Dept Med, Div Gen Internal Med, New York, NY USA. [Carson, April P.; Muntner, Paul] Univ Alabama, Dept Epidemiol & Med, Birmingham, AL USA. [Shimbo, Daichi] Columbia Univ, Dept Med, Div Gen Internal Med, Med Ctr, New York, NY USA. [Fonseca, Vivian] Tulane Univ, Div Endocrinol, New Orleans, LA 70118 USA. [Fonseca, Vivian] Tulane Univ, Dept Med, New Orleans, LA 70118 USA. [Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Fox, Caroline S.] Brigham & Womens Hosp, Dept Endocrinol & Metab, Boston, MA 02115 USA. [Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA. RP Mann, DM (reprint author), Mt Sinai Sch Med, Dept Med, Div Gen Internal Med, New York, NY USA. EM devin.mann@mssm.edu OI Mann, Devin/0000-0002-2099-0852 NR 22 TC 68 Z9 70 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 OCT PY 2010 VL 33 IS 10 BP 2190 EP 2195 DI 10.2337/dc10-0752 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 667PD UT WOS:000283205100012 PM 20628087 ER PT J AU Yeung, EH Zhang, CL Hediger, ML Wactawski-Wende, J Schisterman, EF AF Yeung, Edwina H. Zhang, Cuilin Hediger, Mary L. Wactawski-Wende, Jean Schisterman, Enrique F. TI Racial Differences in the Association Between Sex Hormone-Binding Globulin and Adiposity in Premenopausal Women The BioCycle study SO DIABETES CARE LA English DT Article ID MENSTRUAL-CYCLE; OBESITY; AGE AB OBJECTIVE - To assess the associations between measures of adiposity and sex hormone binding globulin (SHBG) and to evaluate whether such associations differ by race. RESEARCH DESIGN AND METHODS - Adiposity was measured by anthropometry and dual-energy X-ray absorptiometry among women (146 white, 50 black, and 25 Asian) aged 18-44 years in the BioCycle study. SHBG was repeatedly measured over one to two menstrual cycles. The ratio of trunkal to leg fat WO was used to assess upper to lower body adiposity. RESULTS - Among whites, all adiposity measures were significantly and inversely associated with SHBG. Among blacks, BMI (beta = -0.032), waist circumference (beta = -0.016), and T/L (beta = -0.033) were significantly associated with SHBG, whereas total and trunkal fat, were not (P interaction with race <0.04). Among Asians, measures of central and upper body fat were significantly associated with SHBG (e.g., T/L, beta = -0.84) but not BMI. CONCLUSIONS - Associations between SHBG and adiposity differ by race among premenopausal women. Diabetes Care 33:2274-2276, 2010 C1 [Yeung, Edwina H.; Zhang, Cuilin; Hediger, Mary L.; Schisterman, Enrique F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD USA. [Wactawski-Wende, Jean] SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14260 USA. RP Schisterman, EF (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD USA. EM schistee@mail.nih.gov RI Perez , Claudio Alejandro/F-8310-2010; Yeung, Edwina/F-5992-2015; OI Perez , Claudio Alejandro/0000-0001-9688-184X; Yeung, Edwina/0000-0002-3851-2613; Schisterman, Enrique/0000-0003-3757-641X FU Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health FX This work was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health. NR 15 TC 6 Z9 6 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD OCT PY 2010 VL 33 IS 10 BP 2274 EP 2276 DI 10.2337/dc10-0670 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 667PD UT WOS:000283205100027 PM 20664018 ER PT J AU Hafner, A Tinel, A Dai, J Rosenzweig, T DeCabo, R Yankner, B Sinclair, DA AF Hafner, A. Tinel, A. Dai, J. Rosenzweig, T. DeCabo, R. Yankner, B. Sinclair, D. A. TI Sirtuins as modulators of metabolism and longevity SO DIABETES OBESITY & METABOLISM LA English DT Meeting Abstract C1 [Hafner, A.; Tinel, A.; Dai, J.; Rosenzweig, T.; Yankner, B.; Sinclair, D. A.] Harvard Univ, Sch Med, Dept Pathol, Paul F Glenn Labs Biol Mech Aging, Boston, MA 02115 USA. [DeCabo, R.] NIA, NIH, Bethesda, MD 20892 USA. RI de Cabo, Rafael/J-5230-2016 OI de Cabo, Rafael/0000-0002-3354-2442 NR 0 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1462-8902 J9 DIABETES OBES METAB JI Diabetes Obes. Metab. PD OCT PY 2010 VL 12 SU 1 BP 9 EP 9 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 656XE UT WOS:000282373600012 ER PT J AU Quon, MJ AF Quon, M. J. TI Relationships between insulin resistance and endothelial dysfunction: from cells to humans SO DIABETES OBESITY & METABOLISM LA English DT Meeting Abstract C1 [Quon, M. J.] NIH, Diabet Unit, Clin Invest Lab, NCCAM, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1462-8902 J9 DIABETES OBES METAB JI Diabetes Obes. Metab. PD OCT PY 2010 VL 12 SU 1 BP 23 EP 24 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 656XE UT WOS:000282373600029 ER PT J AU McLaughlin, IM Isao, P Reaven, GM Sherman, A Cushman, SW AF McLaughlin, I. M. Isao, P. Reaven, G. M. Sherman, A. Cushman, S. W. TI Clinical implications of the small and large fat cells SO DIABETES OBESITY & METABOLISM LA English DT Meeting Abstract C1 [McLaughlin, I. M.; Isao, P.; Reaven, G. M.] Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA. [Sherman, A.; Cushman, S. W.] NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1462-8902 J9 DIABETES OBES METAB JI Diabetes Obes. Metab. PD OCT PY 2010 VL 12 SU 1 BP 28 EP 29 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 656XE UT WOS:000282373600035 ER PT J AU Liu, A Sonmez, A Yee, G Bazuine, M Arroyo, M Sherman, A McLaughlin, T Reaven, G Cushman, S Tsao, P AF Liu, Alice Sonmez, Alper Yee, Gail Bazuine, Merlijn Arroyo, Matilde Sherman, Arthur McLaughlin, Tracey Reaven, Gerald Cushman, Samuel Tsao, Philip TI Differential adipogenic and inflammatory properties of small adipocytes in Zucker Obese and Lean rats SO DIABETES & VASCULAR DISEASE RESEARCH LA English DT Article DE Adipose cell size; inflammation; insulin resistance; obesity ID ADIPOSE-CELL-SIZE; TUMOR-NECROSIS-FACTOR; INSULIN-RESISTANCE; GLUCOSE-METABOLISM; CARDIOVASCULAR-DISEASE; IMPAIRED ADIPOGENESIS; GENETIC OBESITY; FATTY RAT; TISSUE; EXPRESSION AB We recently reported that a preponderance of small adipose cells, decreased expression of cell differentiation markers, and enhanced inflammatory activity in human subcutaneous whole adipose tissue were associated with insulin resistance To test the hypothesis that small adipocytes exhibited these differential properties, we characterised small adipocytes from epididymal adipose tissue of Zucker Obese (ZO) and Lean (ZL) rats Rat epididymal fat pads were removed and adipocytes isolated by collagenase digestion Small adipocytes were separated by sequential filtration through nylon meshes Adipocytes were fixed in osmium tetroxide for cell size distribution analysis via Beckman Coulter Multisizer Quantitative real-time PCR for cell differentiation and inflammatory genes was performed Small adipocytes represented a markedly greater percentage of the total adipocyte population in ZO than ZL rats (58 +/- 4% vs 12 +/- 3%, p<0 00 1) In ZO rats, small as compared with total adipocytes had 4-fold decreased adiponectin, and 4-fold increased visfatin and IL-6 levels Comparison of small adipocytes in ZO versus ZL rats revealed 3-fold decreased adiponectin and PPAR gamma levels, and 2 5-fold increased IL-6 In conclusion, ZO rat adipose tissue harbours a large proportion of small adipocytes that manifest impaired cell differentiation and pro-inflammatory activity, two mechanisms by which small adipocytes may contribute to insulin resistance C1 [Liu, Alice; McLaughlin, Tracey] Stanford Univ, Med Ctr, Dept Med, Div Endocrinol, Stanford, CA 94305 USA. [Sonmez, Alper; Yee, Gail; Reaven, Gerald; Tsao, Philip] Stanford Univ, Med Ctr, Dept Med, Div Cardiovasc Med, Stanford, CA 94305 USA. [Bazuine, Merlijn; Arroyo, Matilde; Sherman, Arthur; Cushman, Samuel] NIDDKD, NIH, Bethesda, MD USA. RP Liu, A (reprint author), Stanford Univ, Med Ctr, Dept Med, Div Endocrinol, 300 Pasteur Dr,Room S 025, Stanford, CA 94305 USA. OI Sonmez, Alper/0000-0002-9309-7715 FU NIH/NIDDK [1 R01 DK071309-01, 5 R01 DK071333-04, 5 F32 DK079578-02]; NIDDK FX Funding for this study was provided by study grants NIH/NIDDK 1 R01 DK071309-01, 5 R01 DK071333-04, 5 F32 DK079578-02, and by the NIDDK Intramural Research Program NR 37 TC 11 Z9 11 U1 0 U2 2 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1479-1641 J9 DIABETES VASC DIS RE JI Diabetes Vasc. Dis. Res. PD OCT PY 2010 VL 7 IS 4 BP 311 EP 318 DI 10.1177/1479164110386126 PG 8 WC Endocrinology & Metabolism; Peripheral Vascular Disease SC Endocrinology & Metabolism; Cardiovascular System & Cardiology GA 691LG UT WOS:000285080700008 PM 20961992 ER PT J AU Stuart, M Papini, D Benvenuti, F Nerattini, M Roccato, E Macellari, V Stanhope, S Macko, R Weinrich, M AF Stuart, Mary Papini, Donato Benvenuti, Francesco Nerattini, Marco Roccato, Enrico Macellari, Velio Stanhope, Steven Macko, Richard Weinrich, Michael TI Methodological issues in monitoring health services and outcomes for stroke survivors: A case study SO DISABILITY AND HEALTH JOURNAL LA English DT Article DE Stroke; Outcomes; Equity; Administrative data ID POSTACUTE REHABILITATION; INFORMATION-TECHNOLOGY; COPENHAGEN STROKE; ISCHEMIC-STROKE; MOTOR RECOVERY; IMPACT; CARE; COSTS; COMMUNITY; EXERCISE AB Background: Obtaining comprehensive health outcomes and health services utilization data on stroke patients has been difficult. This research grew out of a memorandum of understanding between the National Institutes of Health and the Istituto Superiore di Sanita (its Italian equivalent) to foster collaborative research on rehabilitation. Objective: The purpose of this study was to pilot a methodology using administrative data to monitor and improve health outcomes for stroke survivors in Tuscany. Methods: This study used qualitative and quantitative methods to study health resources available to and used by stroke survivors during the first 12 months poststroke in two Italian health authorities (AUSLs 10 and 11). Mortality rates were used as an outcome measure. Results: Number of inpatient days, number of prescriptions, and prescription costs were significantly higher for patients in AUSL 10 compared with AUSL 11. There was no significant difference between mortality rates. Conclusion: Using administrative data to monitor process and outcomes for chronic stroke has the potential to save money and improve outcomes. However, measures of functional impairment and more sensitive outcome measures than mortality are important. Additional recommendations for enhanced data collection and reporting are discussed. (C) 2010 Elsevier Inc. All rights reserved. C1 [Stuart, Mary] Univ Maryland, Hlth Adm & Policy Program, Baltimore, MD 21250 USA. [Stuart, Mary; Macko, Richard] Dept Vet Affairs, Baltimore, MD 21201 USA. [Papini, Donato] Agenzia Sanit Reg, I-40127 Regione Emilia Romagna, Italy. [Benvenuti, Francesco] Azienda Unita Sanit Locale 11, Dipartmento Riabilitaz, I-50053 Regione Oscana, Empoli, Italy. [Nerattini, Marco] Azienda Osped Univ Senese, Direz Gen, I-53100 Siena, Italy. [Roccato, Enrico] Azienda Unita Sanit Locale 11, Direz Sanit, I-50053 Regione Toscana, Empoli, Italy. [Macellari, Velio] Ist Super Sanita, I-00161 Rome, Italy. [Stanhope, Steven] Univ Delaware, Dept Hlth Nutr & Exercise Sci, Newark, DE 19716 USA. [Macko, Richard] Univ Maryland, Dept Neurol, Div Gerontol, Baltimore, MD 21201 USA. [Macko, Richard] Univ Maryland, Dept Med, Div Gerontol, Baltimore, MD 21201 USA. [Weinrich, Michael] NICHHD, Natl Ctr Med Rehabil Res, NIH, Bethesda, MD 20892 USA. RP Stuart, M (reprint author), Univ Maryland, Hlth Adm & Policy Program, Baltimore, MD 21250 USA. EM stuart@umbc.edu FU Azienda Unita Sanitaria Locale 10 and 11; Regione Toscana; Istituto Superiore di Sanita, Roma, Italy FX None of the authors has any financial competing interests. Drs. Papini, Benvenuti, and Roccato and Mr. Nerattini are employed by Health Authorities in Italy. We want to acknowledge the support of Alessandro Reggiani, Azienda Unita Sanitaria Locale 11, Regione Toscana, and Dr. Carlo Tomassini (previously at Azienda Unita Sanitaria Locale 10 in Florence), Aziende Ospedaliera Universitaria Senese, Siena, Italy, who provided administrative support for this study. This study was financially supported in part by the Azienda Unita Sanitaria Locale 10 and 11, Regione Toscana, and Istituto Superiore di Sanita, Roma, Italy, within the project "Obtaining Optimally Functional Recovery and Efficient Managed Care for the Chronic Stroke Population" (convenzione N. 530/F20/2). Independent observers were provided by the Baltimore Veterans Administration GRECC, Stroke REAP, Exercise and Robotics Center of Excellence, and the University of Maryland, Baltimore County. We thank the John E. Fogarty International Center and the National Center for Medical Rehabilitation Research at NICHD for providing travel support. The following individuals reviewed data from the stroke pilot study and made recommendations regarding future enhancements: Douglas Bradham, Ph.D., Division of Healthcare Outcomes Research, Department of Preventive Medicine and Epidemiology, University of Maryland Medical School; Donald Steinwachs, Ph.D., Director of the Health Services Research and Development Center, Johns Hopkins Bloomberg School of Hygiene and Public Health; Alex Dromerick, M.D., National Rehabilitation Hospital, Washington, DC; Andrew Kramer, M.D., Division of Health Care Policy and Research, Department of Medicine, University of Colorado Health Sciences Center; and Pamela Duncan, Ph.D., Director of Research, Division of Physical Therapy, Duke University. NR 56 TC 3 Z9 3 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-6574 J9 DISABIL HEALTH J JI Disabil. Health J. PD OCT PY 2010 VL 3 IS 4 BP 271 EP 281 DI 10.1016/j.dhjo.2009.11.003 PG 11 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health; Rehabilitation SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Rehabilitation GA 668QR UT WOS:000283285200009 PM 21057665 ER PT J AU Iida, Y Kim, JH Kazuki, Y Hoshiya, H Takiguchi, M Hayashi, M Erliandri, I Lee, HS Samoshkin, A Masumoto, H Earnshaw, WC Kouprina, N Larionov, V Oshimura, M AF Iida, Yuichi Kim, Jung-Hyun Kazuki, Yasuhiro Hoshiya, Hidetoshi Takiguchi, Masato Hayashi, Masahiro Erliandri, Indri Lee, Hee-Sheung Samoshkin, Alex Masumoto, Hiroshi Earnshaw, William C. Kouprina, Natalay Larionov, Vladimir Oshimura, Mitsuo TI Human Artificial Chromosome with a Conditional Centromere for Gene Delivery and Gene Expression SO DNA RESEARCH LA English DT Article DE human artificial chromosome; conditional centromere; gene delivery ID STEM-CELLS; THERAPY; CONSTRUCTION; GENERATION; CLONING; MICE AB Human artificial chromosomes (HACs), which carry a fully functional centromere and are maintained as a single-copy episome, are not associated with random mutagenesis and offer greater control over expression of ectopic genes on the HAC. Recently, we generated a HAC with a conditional centromere, which includes the tetracycline operator (tet-O) sequence embedded in the alphoid DNA array. This conditional centromere can be inactivated, loss of the alphoid(tet-O)) (tet-O HAC) by expression of tet-repressor fusion proteins. In this report, we describe adaptation of the tet-O HAC vector for gene delivery and gene expression in human cells. A loxP cassette was inserted into the tet-O HAC by homologous recombination in chicken DT40 cells following a microcell-mediated chromosome transfer (MMCT). The tet-O HAC with the loxP cassette was then transferred into Chinese hamster ovary cells, and EGFP transgene was efficiently and accurately incorporated into the tet-O HAC vector. The EGFP transgene was stably expressed in human cells after transfer via MMCT. Because the transgenes inserted on the tet-O HAC can be eliminated from cells by HAC loss due to centromere inactivation, this HAC vector system provides important novel features and has potential applications for gene expression studies and gene therapy. C1 [Iida, Yuichi; Kazuki, Yasuhiro; Hoshiya, Hidetoshi; Takiguchi, Masato; Hayashi, Masahiro; Oshimura, Mitsuo] Tottori Univ, Dept Biomed Sci, Inst Regenerat Med & Biofunct, Grad Sch Med Sci, Tottori 680, Japan. [Kim, Jung-Hyun; Erliandri, Indri; Lee, Hee-Sheung; Samoshkin, Alex; Kouprina, Natalay; Larionov, Vladimir] NCI, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA. [Masumoto, Hiroshi] Kazusa DNA Res Inst, Dept Human Genome Res, Lab Cell Engn, Chiba 2920818, Japan. [Earnshaw, William C.] Univ Edinburgh, Wellcome Trust Ctr Cell Biol, Edinburgh EH9 3JR, Midlothian, Scotland. RP Oshimura, M (reprint author), Tottori Univ, Dept Biomed Sci, Inst Regenerat Med & Biofunct, Grad Sch Med Sci, Nishi Cho, Tottori 680, Japan. EM oshimura@grape.med.tottori-u.ac.jp FU Ministry of Education, Culture, Sports, Science and Technology of Japan; Wellcome Trust; NIH, National Cancer Institute, Center for Cancer Research FX This study was supported by the 21st Century COE program from the Ministry of Education, Culture, Sports, Science and Technology of Japan (M.O.), the Grand-in-Aid for Scientific Research from Ministry of Education, Culture, Sports, Science and Technology of Japan (M.O. and H.M.). Work in the WCE lab was supported by The Wellcome Trust. This research was also supported by the intramural research program of the NIH, National Cancer Institute, Center for Cancer Research. NR 26 TC 32 Z9 32 U1 2 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1340-2838 J9 DNA RES JI DNA Res. PD OCT PY 2010 VL 17 IS 5 BP 293 EP 301 DI 10.1093/dnares/dsq020 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 673AT UT WOS:000283631300004 PM 20798231 ER PT J AU Hon, YY Sun, H Dejam, A Gladwin, MT AF Hon, Yuen Yi Sun, He Dejam, Andre Gladwin, Mark T. TI Characterization of Erythrocytic Uptake and Release and Disposition Pathways of Nitrite, Nitrate, Methemoglobin, and Iron-Nitrosyl Hemoglobin in the Human Circulation SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID AUTOCATALYTIC OXIDATION; ISCHEMIA-REPERFUSION; OXIDE; OXYHEMOGLOBIN; DEOXYHEMOGLOBIN; METABOLISM; MECHANISM; REDUCTASE; KINETICS; BLOOD AB Nitrite-hemoglobin reactions have been studied extensively in vitro, but there is a lack of information on the kinetics of nitrite and its metabolites in humans. In this study, we developed a nine-compartment physiological pharmacokinetic model to describe the in vivo erythrocytic uptake and release and disposition pathways of nitrite, nitrate, methemoglobin, and iron-nitrosyl hemoglobin in the human circulation. Our model revealed that nitrite entered erythrocytes rapidly with a rate constant of 0.256 min(-1) (i.e., half-life = 2.71 min). The formation of iron-nitrosyl hemoglobin from nitrite, which involves the reduction of nitrite by deoxyhemoglobin to generate nitric oxide (NO) and reaction of NO with deoxyhemoglobin to form iron-nitrosyl hemoglobin, occurred rapidly as well (k = 2.02 min(-1); half-life = 0.343 min = 21 s). The disposition kinetics of methemoglobin was complex. Nitrate formation occurred primarily in erythrocytes through the nitrite-oxyhemoglobin reaction and was higher when nitrite was administered intra-arterially than intravenously. Nitrate reduction was an insignificant metabolic pathway. This study is the first to comprehensively evaluate the kinetics of nitrite and its metabolites in humans and provides unique insights into the rapid equilibrium of nitrite into erythrocytes and conversion to NO in the red cell, which is kinetically associated with vasodilation. C1 [Hon, Yuen Yi] NIH, Clin Pharmacokinet Res Lab, Ctr Clin, Dept Pharm, Bethesda, MD 20892 USA. [Dejam, Andre; Gladwin, Mark T.] NIH, NHLBI, Vasc Med Branch, Bethesda, MD 20892 USA. [Sun, He] Tianjin Univ, Sch Pharmaceut Sci & Technol, Tianjin 300072, Peoples R China. RP Hon, YY (reprint author), NIH, Clin Pharmacokinet Res Lab, Ctr Clin, Dept Pharm, Bldg 10,Rm 1C240,10 Ctr Dr, Bethesda, MD 20892 USA. EM chon@cc.nih.gov FU National Institutes of Health Clinical Center; National Heart, Lung, and Blood Institute FX This work was supported by the Intramural Research Program of the National Institutes of Health Clinical Center and National Heart, Lung, and Blood Institute. NR 30 TC 12 Z9 12 U1 3 U2 14 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD OCT PY 2010 VL 38 IS 10 BP 1707 EP 1713 DI 10.1124/dmd.110.034355 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 651ZQ UT WOS:000281969200012 PM 20634335 ER PT J AU Sinnott, B Ron, E Schneider, AB AF Sinnott, Bridget Ron, Elaine Schneider, Arthur B. TI Exposing the Thyroid to Radiation: A Review of Its Current Extent, Risks, and Implications SO ENDOCRINE REVIEWS LA English DT Review ID ATOMIC-BOMB SURVIVORS; FINE-NEEDLE-ASPIRATION; POPULATION-BASED COHORT; SOLID CANCER INCIDENCE; DIAGNOSTIC X-RAYS; COMPUTED-TOMOGRAPHY; IONIZING-RADIATION; UNITED-STATES; PEDIATRIC-PATIENTS; CHILDHOOD-CANCER AB Radiation exposure of the thyroid at a young age is a recognized risk factor for the development of differentiated thyroid cancer lasting for four decades and probably for a lifetime after exposure. Medical radiation exposure, however, occurs frequently, including among the pediatric population, which is especially sensitive to the effects of radiation. In the past, the treatment of benign medical conditions with external radiation represented the most significant thyroid radiation exposures. Today, diagnostic medical radiation represents the largest source of man-made radiation exposure. Radiation exposure related to the use of computerized tomography is rising exponentially, particularly in the pediatric population. There is direct epidemiological evidence of a small but significant increased risk of cancer at radiation doses equivalent to computerized tomography doses used today. Paralleling the increasing use of medical radiation is an increase in the incidence of papillary thyroid cancer. At present, it is unclear how much of this increase is related to increased detection of subclinical disease from the increased utilization of ultrasonography and fine-needle aspiration, how much is due to a true increase in thyroid cancer, and how much, if any, can be ascribed to medical radiation exposure. Fortunately, the amount of radiation exposure from medical sources can be reduced. In this article we review the sources of thyroid radiation exposure, radiation risks to the thyroid gland, strategies for reducing radiation exposure to the thyroid, and ways that endocrinologists can participate in this effort. Finally, we provide some suggestions for future research directions. (Endocrine Reviews 31: 756-773, 2010) C1 [Schneider, Arthur B.] Univ Illinois, Dept Med, Sect Endocrinol Diabet & Metab, Coll Med, Chicago, IL 60612 USA. [Sinnott, Bridget] Mercy Hosp, Dept Med, Chicago, IL 60616 USA. [Sinnott, Bridget] Med Ctr, Chicago, IL 60616 USA. [Ron, Elaine] Natl Canc Inst, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RP Schneider, AB (reprint author), Univ Illinois, Dept Med, Sect Endocrinol Diabet & Metab, Coll Med, 1819 W Polk St MC 640, Chicago, IL 60612 USA. EM abschnei@uic.edu FU National Institutes of Health; National Cancer Institute [CA 21815] FX E.R. is supported by the intramural research program of the National Institutes of Health, and the research of A.B.S. has been supported by a grant from the National Cancer Institute (CA 21815). NR 167 TC 48 Z9 50 U1 0 U2 5 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0163-769X EI 1945-7189 J9 ENDOCR REV JI Endocr. Rev. PD OCT PY 2010 VL 31 IS 5 BP 756 EP 773 DI 10.1210/er.2010-0003 PG 18 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 660XS UT WOS:000282681600005 PM 20650861 ER PT J AU Olivero, OA Larramendy, M Soloneski, S Menck, CFM Matta, J Folle, GA Zamorano-Ponce, E Spivak, G AF Olivero, Ofelia A. Larramendy, Marcelo Soloneski, Sonia Menck, Carlos F. M. Matta, Jaime Folle, Gustavo A. Zamorano-Ponce, Enrique Spivak, Graciela TI Impact of EMS Outreach: Successful Developments in Latin America SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Editorial Material DE pesticides; centrosomes; chromatin organization; breast cancer; DNA repair mutants ID OVARY CHO CELLS; DITHIOCARBAMATE PESTICIDE ZINEB; UV-SENSITIVE SYNDROME; COMMERCIAL FORMULATION; DNA-DAMAGE; IN-VITRO; CAULOBACTER-CRESCENTUS; GENOTOXIC EVALUATION; HERBICIDE DICAMBA; REPAIR AB This collection of articles was inspired by the long-standing relationship between the Environmental Mutagen Society and Latin American scientists, and by the program for the 39th Environmental Mutagen Society meeting in Puerto Rico in 2008, which included a symposium featuring "South of the border" scientists. This collection, compiled by Graciela Spivak and Ofelia Olivero, both originally from Argentina, highlights scientists who work in or were trained in Latin American countries and in Puerto Rico in a variety of scientific specialties related to DNA repair and cancer susceptibility, genomic organization and stability, genetic diversity, and environmental contaminants. Environ. Mol. Mutagen. 51:763-773, 2010. (c) 2010 Wiley-Liss, Inc. C1 [Spivak, Graciela] Stanford Univ, Dept Biol, Stanford, CA 94305 USA. [Olivero, Ofelia A.] Natl Canc Inst, NIH, Lab Canc Biol & Genet, Carcinogen DNA Interact Sect, Bethesda, MD USA. [Larramendy, Marcelo; Soloneski, Sonia] Univ Nacl La Plata, Fac Ciencias Nat & Museo, Catedra Citol, La Plata, Buenos Aires, Argentina. [Menck, Carlos F. M.] Univ Sao Paulo, Inst Biomed Sci, Dept Microbiol, Sao Paulo, Brazil. [Matta, Jaime] Ponce Sch Med, Dept Pharmacol Physiol & Toxicol, Ponce, PR USA. [Folle, Gustavo A.] Inst Invest Biol Clemente Estable, Dept Genet, Montevideo, Uruguay. [Zamorano-Ponce, Enrique] Univ Bio Bio, Fac Ciencias, Dept Ciencias Bas, Lab Genet Toxicol GENETOX, Biobio, Chile. RP Spivak, G (reprint author), Stanford Univ, Dept Biol, 371 Serra Mall, Stanford, CA 94305 USA. EM gspivak@stanford.edu RI Menck, Carlos/G-6321-2011; OI Spivak, Graciela/0000-0001-6093-5965; Menck, Carlos FM/0000-0003-1941-0694 FU Intramural NIH HHS [Z99 CA999999]; NCI NIH HHS [U56 CA126379, SC1 CA157250]; NIGMS NIH HHS [S06 GM008103] NR 49 TC 0 Z9 0 U1 0 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD OCT-DEC PY 2010 VL 51 IS 8-9 SI SI BP 763 EP 773 DI 10.1002/em.20563 PG 11 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 666GI UT WOS:000283102100005 PM 20213840 ER PT J AU Witt, KL Moorman, PG Kovalchuk, O Holland, N Block, G Andreassen, PR AF Witt, Kristine L. Moorman, Patricia G. Kovalchuk, Olga Holland, Nina Block, Gladys Andreassen, Paul R. TI Genetics and Women's Health Issues-The Commitment of EMS to Women Scientists and Gender-Associated Disease Topics SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Editorial Material DE ovarian cancer; breast cancer; BRCA1; microRNA; epigenetics; DNA repair; obesity; oxidative stress ID OVARIAN-CANCER SUSCEPTIBILITY; C-REACTIVE PROTEIN; BREAST-CANCER; OXIDATIVE STRESS; VITAMIN-C; DRUG-USE; BRCA2; PALB2; POLYMORPHISMS; RISK AB This manuscript presents an overview of a symposium held at the 2009 annual meeting of the Environmental Mutagen Society (EMS) in St. Louis, MO. The symposium was sponsored by the Women in the Environmental Mutagen Society (WEMS) special interest group, and it covered current molecular genetics technologies and their impact on diagnosis and treatment of diseases that primarily or differentially affect women. Four speakers presented ground-breaking new information from such areas as cancer genetics, gene-environment interactions, epigenetics, DNA repair, and molecular epidemiology. Although cancer was a primary focus of the symposium, other health issues such as obesity and cardiovascular disease were addressed. The rapid evolution in genomic technologies discussed in this symposium should provide new tools to explore some of the critical questions raised by the research projects described in this article. This symposium demonstrates that EMS provides a forum for the presentation, discussion, and extension of the data generated by the investigators featured in this article and other researchers engaged in the study of the molecular mechanisms and gene-environment interactions that impact women's health. Environ. Mol. Mutagen. 51:774-780, 2010. (c) 2010 Wiley-Liss, Inc. C1 [Witt, Kristine L.] NIEHS, Natl Toxicol Program, NIH, Res Triangle Pk, NC 27709 USA. [Moorman, Patricia G.] Duke Univ, Dept Community & Family Med, Durham, NC USA. [Kovalchuk, Olga] Univ Lethbridge, Dept Biol Sci, Lethbridge, AB T1K 3M4, Canada. [Holland, Nina; Block, Gladys] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. [Andreassen, Paul R.] Cincinnati Childrens Hosp, Med Ctr, Div Expt Hematol & Canc, Cincinnati, OH USA. RP Witt, KL (reprint author), NIEHS, Natl Toxicol Program, NIH, POB 12233,Mail Drop K2-15, Res Triangle Pk, NC 27709 USA. EM witt@niehs.nih.gov RI Block, Gladys/E-3304-2010 FU Canadian Institutes of Health Research; Intramural NIH HHS; NCI NIH HHS [R01 CA076016, R01-CA76016]; NCRR NIH HHS [M01 RR001271, NCI M01-RR01271]; NIDDK NIH HHS [R01 DK062378, R01-DK062378]; NIEHS NIH HHS [P01 ES009605, P01-ES009605, R01 ES012503, R01-ES012503] NR 37 TC 0 Z9 0 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD OCT-DEC PY 2010 VL 51 IS 8-9 SI SI BP 774 EP 780 DI 10.1002/em.20607 PG 7 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 666GI UT WOS:000283102100006 PM 20740639 ER PT J AU Ward, EM Schulte, PA Straif, K Hopf, NB Caldwell, JC Carreon, T DeMarini, DM Fowler, BA Goldstein, BD Hemminki, K Hines, CJ Pursiainen, KH Kuempel, E Lewtas, J Lunn, RM Lynge, E McElvenny, DM Muhle, H Nakajima, T Robertson, LW Rothman, N Ruder, AM Schubauer-Berigan, MK Siemiatycki, J Silverman, D Smith, MT Sorahan, T Steenland, K Stevens, RG Vineis, P Zahm, SH Zeise, L Cogliano, VJ AF Ward, Elizabeth M. Schulte, Paul A. Straif, Kurt Hopf, Nancy B. Caldwell, Jane C. Carreon, Tania DeMarini, David M. Fowler, Bruce A. Goldstein, Bernard D. Hemminki, Kari Hines, Cynthia J. Pursiainen, Kirsti Husgafvel Kuempel, Eileen Lewtas, Joellen Lunn, Ruth M. Lynge, Elsebeth McElvenny, Damien M. Muhle, Hartwig Nakajima, Tamie Robertson, Larry W. Rothman, Nathaniel Ruder, Avima M. Schubauer-Berigan, Mary K. Siemiatycki, Jack Silverman, Debra Smith, Martyn T. Sorahan, Tom Steenland, Kyle Stevens, Richard G. Vineis, Paolo Zahm, Shelia Hoar Zeise, Lauren Cogliano, Vincent J. TI Research Recommendations for Selected IARC-Classified Agents SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Review DE animal; carcinogen; carcinogenesis; epidemiology; human; IARC; mechanisms of carcinogenicity; occupational ID POLYCHLORINATED-BIPHENYLS PCBS; REFRACTORY CERAMIC FIBER; PARTICLE SURFACE-AREA; NESTED CASE-CONTROL; LUNG-CANCER; BREAST-CANCER; OCCUPATIONAL-EXPOSURE; TITANIUM-DIOXIDE; OXIDATIVE STRESS; RISK-ASSESSMENT AB OBJECTIVES: There are some common occupational agents and exposure circumstances for which evidence of carcinogenicity is substantial but not yet conclusive for humans. Our objectives were to identify research gaps and needs for 20 agents prioritized for review based on evidence of widespread human exposures and potential carcinogenicity in animals or humans. DATA SOURCES: For each chemical agent (or category of agents), a systematic review was conducted of new data published since the most recent pertinent International Agency for Research on Cancer (IARC) Monograph meeting on that agent. DATA EXTRACTION: Reviewers were charged with identifying data gaps and general and specific approaches to address them, focusing on research that would be important in resolving classification uncertainties. An expert meeting brought reviewers together to discuss each agent and the identified data gaps and approaches. DATA SYNTHESIS: Several overarching issues were identified that pertained to multiple agents; these included the importance of recognizing that carcinogenic agents can act through multiple toxicity pathways and mechanisms, including epigenetic mechanisms, oxidative stress, and immuno- and hormonal modulation. CONCLUSIONS: Studies in occupational populations provide important opportunities to understand the mechanisms through which exogenous agents cause cancer and intervene to prevent human exposure and/or prevent or detect cancer among those already exposed. Scientific developments are likely to increase the challenges and complexities of carcinogen testing and evaluation in the future, and epidemiologic studies will be particularly critical to inform carcinogen classification and risk assessment processes. C1 [Ward, Elizabeth M.] Amer Canc Soc, Epidemiol & Surveillance Res, Atlanta, GA 30303 USA. [Schulte, Paul A.; Carreon, Tania; Hines, Cynthia J.; Kuempel, Eileen; Ruder, Avima M.; Schubauer-Berigan, Mary K.] NIOSH, Cincinnati, OH 45226 USA. [Straif, Kurt; Cogliano, Vincent J.] Int Agcy Res Canc, F-69372 Lyon, France. [Hopf, Nancy B.] Inst Univ Romand Sante Travail, Lausanne, Switzerland. [Caldwell, Jane C.; DeMarini, David M.] US EPA, Res Triangle Pk, NC 27711 USA. [Fowler, Bruce A.] Agcy Tox Subst & Dis Registry, Chamblee, GA USA. [Goldstein, Bernard D.] Univ Pittsburgh, Pittsburgh, PA USA. [Hemminki, Kari] German Canc Res Ctr, D-6900 Heidelberg, Germany. [Pursiainen, Kirsti Husgafvel] Finnish Inst Occupat Hlth, Helsinki, Finland. [Lewtas, Joellen] Univ Washington, Seattle, WA 98195 USA. [Lunn, Ruth M.] Natl Inst Environm Hlth Sci, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC USA. [Lynge, Elsebeth] Univ Copenhagen, Copenhagen, Denmark. [McElvenny, Damien M.] Univ Cent Lancashire, Lancaster, Lancs, England. [Muhle, Hartwig] Fraunhofer Inst Toxicol & Expt Med, Hannover, Germany. [Nakajima, Tamie] Nagoya Univ, Grad Sch Med, Nagoya, Aichi 4648601, Japan. [Robertson, Larry W.] Univ Iowa, Iowa City, IA USA. [Rothman, Nathaniel; Silverman, Debra; Zahm, Shelia Hoar] NCI, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Siemiatycki, Jack] Univ Montreal Hosp Res Ctr, Montreal, PQ, Canada. [Smith, Martyn T.] Univ Calif Berkeley, Berkeley, CA 94720 USA. [Sorahan, Tom] Univ Birmingham, Inst Occupat & Environm Med, Birmingham, W Midlands, England. [Steenland, Kyle] Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. [Stevens, Richard G.] Univ Connecticut, Ctr Hlth, Farmington, CT USA. [Vineis, Paolo] Univ London Imperial Coll Sci Technol & Med, London, England. [Zeise, Lauren] Calif Environm Protect Agcy, Oakland, CA USA. RP Ward, EM (reprint author), Amer Canc Soc, Epidemiol & Surveillance Res, 250 Williams St, Atlanta, GA 30303 USA. EM elizabeth.ward@cancer.org RI Schubauer-Berigan, Mary/B-3149-2009; Ruder, Avima/I-4155-2012; Zahm, Shelia/B-5025-2015; OI Schubauer-Berigan, Mary/0000-0002-5175-924X; Ruder, Avima/0000-0003-0419-6664; Lynge, Elsebeth/0000-0003-4785-5236 FU American Cancer Society; National Institute for Occupational Safety and Health; International Agency for Research on Cancer; National Institute of Environmental Health Sciences [National Institutes of Health (NIH)]; Division of Cancer Epidemiology and Genetics, National Cancer Institute (NIH) FX This research was supported by the American Cancer Society, the National Institute for Occupational Safety and Health, the Monographs Program of the International Agency for Research on Cancer, the Intramural Research Program of the National Institute of Environmental Health Sciences [National Institutes of Health (NIH)], and the Division of Cancer Epidemiology and Genetics, National Cancer Institute (NIH). NR 112 TC 38 Z9 39 U1 2 U2 15 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD OCT PY 2010 VL 118 IS 10 BP 1355 EP 1362 DI 10.1289/ehp.0901828 PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 656YL UT WOS:000282376900024 PM 20562050 ER PT J AU Vazquez-Prokopec, GM Eng, JLV Kelly, R Mead, DG Kolhe, P Howgate, J Kitron, U Burkot, TR AF Vazquez-Prokopec, Gonzalo M. Eng, Jodi L. Vanden Kelly, Rosmarie Mead, Daniel G. Kolhe, Priti Howgate, James Kitron, Uriel Burkot, Thomas R. TI The Risk of West Nile Virus Infection Is Associated with Combined Sewer Overflow Streams in Urban Atlanta, Georgia, USA SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE arbovirus; Culex quinquefasciatus; risk factors; spatial clustering; spatial epidemiology; urban pollution ID LOUIS ENCEPHALITIS-VIRUS; CULEX-PIPIENS MOSQUITOS; DIPTERA-CULICIDAE; QUINQUEFASCIATUS DIPTERA; SOUTHERN CALIFORNIA; UNITED-STATES; TRANSMISSION; HOST; EPIDEMIOLOGY; LANDSCAPES AB BACKGROUND: At present, the factors favoring transmission and amplification of West Nile Virus (WNV) within urban environments are poorly understood. In urban Atlanta, Georgia, the highly polluted waters of streams affected by combined sewer overflow (CSO) represent significant habitats for the WNV mosquito vector Culex quinquefasciatus. However, their contribution to the risk of WNV infection in humans and birds remains unclear. OBJECTIVES: Our goals were to describe and quantify the spatial distribution of WNV infection in mosquitoes, humans, and corvids, such as blue jays and American crows that are particularly susceptible to WNV infection, and to assess the relationship between WNV infection and proximity to CSO-affected streams in the city of Atlanta, Georgia. MATERIALS AND METHODS: We applied spatial statistics to human, corvid, and mosquito WNV surveillance data from 2001 through 2007. Multimodel analysis was used to estimate associations of WNV infection in Cx. quinquefasciatus, humans, and dead corvids with selected risk factors including distance to CSO streams and catch basins, land cover, median household income, and housing characteristics. RESULTS: We found that WNV infection in mosquitoes, corvids, and humans was spatially clustered and statistically associated with CSO-affected streams. WNV infection in Cx. quinquefasciatus was significantly higher in CSO compared with non-CSO streams, and WNV infection rates among humans and corvids were significantly associated with proximity to CSO-affected streams, the extent of tree cover, and median household income. CONCLUSIONS: Our study strongly suggests that CSO-affected streams are significant sources of Cx. quinquefasciatus mosquitoes that may facilitate WNV transmission to humans within urban environments. Our findings may have direct implications for the surveillance and control of WNV in other urban centers that continue to use CSO systems as a waste management practice. C1 [Vazquez-Prokopec, Gonzalo M.] Emory Univ, Dept Environm Studies, Math & Sci Ctr, Atlanta, GA 30322 USA. [Eng, Jodi L. Vanden; Burkot, Thomas R.] Ctr Dis Control & Prevent, Atlanta, GA USA. [Kelly, Rosmarie] Georgia Div Publ Hlth, Atlanta, GA USA. [Mead, Daniel G.] Univ Georgia, Athens, GA 30602 USA. [Kolhe, Priti; Howgate, James] Fulton Cty Dept Hlth & Wellness, Atlanta, GA USA. [Kitron, Uriel] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Vazquez-Prokopec, GM (reprint author), Emory Univ, Dept Environm Studies, Math & Sci Ctr, 400 Dowman Dr,5th Floor,Suite E536, Atlanta, GA 30322 USA. EM gmvazqu@emory.edu RI Burkot, Thomas/C-6838-2013; Mead, Daniel/F-7501-2013 FU Centers for Disease Control and Prevention (CDC); Emory University (Department of Environmental Studies internal support); Science and Technology Directorate; U.S. Department of Homeland Security; Fogarty International Center; National Institutes of Health FX This work was supported in part by the Centers for Disease Control and Prevention (CDC) and Emory University (Department of Environmental Studies internal support), Research and Policy for Infectious Disease Dynamics (RAPIDD) program of the Science and Technology Directorate, U.S. Department of Homeland Security, and the Fogarty International Center, National Institutes of Health. NR 47 TC 14 Z9 14 U1 1 U2 36 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 OCT PY 2010 VL 118 IS 10 BP 1382 EP 1388 DI 10.1289/ehp.1001939 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 656YL UT WOS:000282376900028 PM 20529765 ER PT J AU Engel, J McDermott, MP Wiebe, S Langfitt, JT Erba, G Gardiner, I Stern, J Dewar, S Sperling, MR Jacobs, M Kieburtz, K AF Engel, Jerome, Jr. McDermott, Michael P. Wiebe, Samuel Langfitt, John T. Erba, Giuseppe Gardiner, Irenita Stern, John Dewar, Sandra Sperling, Michael R. Jacobs, Margaret Kieburtz, Karl CA Early Randomized Surgical Epilepsy TI Design considerations for a multicenter randomized controlled trial of early surgery for mesial temporal lobe epilepsy SO EPILEPSIA LA English DT Article DE Temporal lobe epilepsy; Early surgery; Randomized controlled trial ID QUALITY-OF-LIFE; ANTIEPILEPTIC DRUGS; REFRACTORY EPILEPSY; SURGICAL-TREATMENT; LOBECTOMY; RELIABILITY; INVENTORY; CHILDREN; SEIZURES; VALIDITY AB P>Purpose: To describe the trial design for the multicenter Early Randomized Surgical Epilepsy Trial (ERSET). Patients with pharmacoresistant epilepsy are generally referred for surgical treatment an average of two decades after onset of seizures, often too late to avoid irreversible disability. ERSET was designed to assess the safety and efficacy of early surgical intervention compared to continued pharmacotherapy. Methods: ERSET is a randomized controlled, parallel group clinical trial with blinded outcome adjudication. Participants are patients with mesial temporal lobe epilepsy (MTLE) older than the age of 12 who have had pharmacoresistant seizures for not > 2 years and are determined by detailed evaluation to be surgical candidates prior to randomization. The primary outcome measure is seizure freedom in the second year of a 2-year follow-up period. Health-related quality of life (HRQOL), neurocognitive function, ancillary outcomes, and adverse events were also measured. Results: Significant methodologic problems addressed by the study design included the following: recruitment of participants early in the course of epilepsy; establishment of operational definitions for "pharmacoresistant" and "early"; and standardization of diagnostic testing, medical treatment, and surgical interventions across multiple centers. Discussion: Rigorous trial designs to assess surgical interventions in epilepsy are necessary to provide evidence to guide treatment. This article is the first of a series; trial results will be reported in subsequent publications. C1 [Engel, Jerome, Jr.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Engel, Jerome, Jr.] Univ Calif Los Angeles, Dept Neurobiol, Los Angeles, CA 90095 USA. [Engel, Jerome, Jr.] Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. [Engel, Jerome, Jr.] Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90024 USA. [McDermott, Michael P.] Univ Rochester, Dept Biostat and Computat Biol, Rochester, NY USA. [McDermott, Michael P.; Langfitt, John T.; Erba, Giuseppe; Kieburtz, Karl] Univ Rochester, Dept Neurol, Rochester, NY USA. [Wiebe, Samuel] Univ Calgary, Dept Clin Neurosci, Calgary, AB, Canada. [Erba, Giuseppe; Gardiner, Irenita] Univ Rochester, Dept Pediat, Rochester, NY USA. [Sperling, Michael R.] Thomas Jefferson Univ, Dept Neurol, Philadelphia, PA 19107 USA. [Jacobs, Margaret] NINDS, NIH, Bethesda, MD 20892 USA. RP Engel, J (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, 710 Westwood Plaza, Los Angeles, CA 90095 USA. EM engel@ucla.edu RI shengkun, yu/B-8440-2012; French, Jacqueline/G-6795-2013 OI French, Jacqueline/0000-0003-2242-8027 FU National Institutes of Neurological Disorders and Stroke [R21 NS037897, U01 NS042372] FX This work was supported by grants R21 NS037897 and U01 NS042372 from the National Institutes of Neurological Disorders and Stroke. NR 44 TC 15 Z9 16 U1 3 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD OCT PY 2010 VL 51 IS 10 BP 1978 EP 1986 DI 10.1111/j.1528-1167.2010.02641.x PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 660KE UT WOS:000282639700007 PM 20550556 ER PT J AU Theodore, WH AF Theodore, William H. TI The postictal state: Effects of age and underlying brain dysfunction SO EPILEPSY & BEHAVIOR LA English DT Review DE Postictal; Children; Elderly; Metabolism; Blood flow; Lesion; Focal neurologic signs ID POSITRON-EMISSION-TOMOGRAPHY; TEMPORAL-LOBE EPILEPSY; CEREBRAL-BLOOD-FLOW; COMPLEX PARTIAL SEIZURES; CLINICAL-MANIFESTATIONS; OCCIPITAL EPILEPSY; PSYCHOTIC EPISODES; OXYGEN-METABOLISM; CHILDREN; CHILDHOOD AB There is relatively little information on the underlying parameters that affect clinical features of the postictal period. Age-related physiological changes, including alterations in cerebral blood flow and metabolism, neurotransmitter function, and responses of the brain to seizure activity may affect postictal clinical phenomena. Some conclusions can be drawn. Elderly adults and children, particularly in the presence of diffuse cerebral dysfunction, may have more prolonged postictal confusion. Postictal dysphasia strongly suggests a dominant hemisphere focus, more often temporal, and Todd's paralysis is always contralateral to the epileptogenic zone. Much additional information could be derived from the vast amount of video/EEG monitoring data available. Published by Elsevier Inc. C1 NIH, Clin Epilepsy Sect, Bethesda, MD 20892 USA. RP Theodore, WH (reprint author), NIH, Clin Epilepsy Sect, Bldg 10,Room 7C-103, Bethesda, MD 20892 USA. EM theodorw@ninds.nih.gov NR 54 TC 11 Z9 12 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 1525-5050 J9 EPILEPSY BEHAV JI Epilepsy Behav. PD OCT PY 2010 VL 19 IS 2 BP 118 EP 120 DI 10.1016/j.yebeh.2010.06.031 PG 3 WC Behavioral Sciences; Clinical Neurology; Psychiatry SC Behavioral Sciences; Neurosciences & Neurology; Psychiatry GA 667OV UT WOS:000283204300006 PM 20724220 ER PT J AU Krauss, G Theodore, WH AF Krauss, Gregory Theodore, William H. TI Treatment strategies in the postictal state SO EPILEPSY & BEHAVIOR LA English DT Review DE Seizures; Delirium; Postictal; Psychosis; Epilepsy; Treatment ID ANTIEPILEPTIC DRUGS; PSYCHOTIC EPISODES; EPILEPSY; SEIZURES; DISORDERS; POST; PSYCHOPATHOLOGY; AGGRESSION; DELIRIUM AB Postictal behaviors and symptoms often require special assessment and treatment. We review risk factors for postictal delirium and psychosis and management of agitated and confused behaviors in patients after seizures. Medical and emergency staff require careful training to manage behaviors associated with postictal delirium and psychosis in order to protect patients while their confusion resolves. Treatment of postictal states requires recognition of underlying neurological and systemic disorders associated with seizures and delirium such as metabolic disorders and nonconvulsive seizures. There is incomplete information about the causes and optimal treatments for seizure-related psychosis, however, postictal behaviors can usually be managed safely. (C) 2010 Elsevier Inc. All rights reserved. C1 [Krauss, Gregory] Johns Hopkins Univ, Dept Neurol, Sch Med, Baltimore, MD 21287 USA. [Theodore, William H.] NIH, Clin Epilepsy Sect, Bethesda, MD 20892 USA. RP Krauss, G (reprint author), Johns Hopkins Univ, Dept Neurol, Sch Med, 600 N Wolfe St,Meyer 2-147, Baltimore, MD 21287 USA. EM gkrauss@jhmi.edu FU Intramural NIH HHS [Z01 NS002236-33] NR 39 TC 11 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 1525-5050 J9 EPILEPSY BEHAV JI Epilepsy Behav. PD OCT PY 2010 VL 19 IS 2 BP 188 EP 190 DI 10.1016/j.yebeh.2010.06.030 PG 3 WC Behavioral Sciences; Clinical Neurology; Psychiatry SC Behavioral Sciences; Neurosciences & Neurology; Psychiatry GA 667OV UT WOS:000283204300023 PM 20719574 ER PT J AU Charmandari, E Kino, T AF Charmandari, Evangelia Kino, Tomoshige TI Chrousos syndrome: a seminal report, a phylogenetic enigma and the clinical implications of glucocorticoid signalling changes SO EUROPEAN JOURNAL OF CLINICAL INVESTIGATION LA English DT Review DE Glucocorticoid receptor; primary generalized glucocorticoid resistance; glucocorticoid signal transduction ID LIGAND-BINDING DOMAIN; PRIMARY CORTISOL RESISTANCE; RECEPTOR GENE; POINT MUTATION; HORMONE RESISTANCE; STEROID-RECEPTOR; PUBERTAL CHANGES; EVOLUTION; GR; EXPLOITATION AB P>Background Glucocorticoids regulate a broad spectrum of physiologic functions and play important roles in resting and stress homeostasis. Their actions are mediated by the nuclear glucocorticoid receptor (GR). Design Using a patient as a stimulus, we reviewed briefly the area of Primary Generalized Glucocorticoid Resistance in man and nonhuman primates. Results In man, Primary Generalized Glucocorticoid Resistance is a rare sporadic or familial syndrome characterized by target-tissue insensitivity to glucocorticoids and compensatory elevations in adrenocorticotropic hormone (ACTH), leading to increased secretion of cortisol and adrenal steroids with mineralocorticoid and/or androgenic activity, and causing hypermineralocorticoidism and hyperandrogenism without Cushing stigmata. The presentation, diagnosis and therapy of this condition are summarized. Many or, most likely, all New World primates have markedly elevated cortisol and ACTH, and resistance to dexamethasone suppression, without any pathology. These primates in fact have 'pan-steroid/sterol' resistance, including all five steroid hormones and 1,25-dihydroxy-vitamin D. In humans, the molecular basis of Primary Generalized Glucocorticoid Resistance has been mainly ascribed to recent mutations in the GR gene, which impair glucocorticoid signal transduction. In contrast, in the primates, steroid/sterol signalling systems have adapted under yet unknown selective pressures or genetic drift over many million years. Of course, other molecules of the signaling pathways may also be involved in both states. There are now a host of human states associated with tissue-specific pathologic glucocorticoid target tissue changes. These include allergic, autoimmune, inflammatory and lymphoproliferative disorders. Conclusions In recognition of Professor George P. Chrousos' extensive ground-breaking research in this field, and for the sake of brevity, we propose that 'Chrousos syndrome' is used instead of 'Primary Generalized Familial or Sporadic Glucocorticoid Resistance'. C1 [Charmandari, Evangelia] Acad Athens, Biomed Res Fdn, Clin Res Ctr, Div Endocrinol & Metab, Athens 11527, Greece. [Charmandari, Evangelia] Univ Athens, Sch Med, Aghia Sophia Childrens Hosp, Div Endocrinol Metab & Diabet,Dept Pediat 1, GR-11527 Athens, Greece. [Charmandari, Evangelia; Kino, Tomoshige] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, Unit Mol Hormone Act, NIH, Bethesda, MD 20892 USA. RP Charmandari, E (reprint author), Acad Athens, Biomed Res Fdn, Clin Res Ctr, Div Endocrinol & Metab, 4 Soranou Tou Efessiou St, Athens 11527, Greece. EM evangelia.charmandari@googlemail.com RI Charmandari, Evangelia/B-6701-2011 FU Biomedical Research Foundation of the Academy of Athens, Athens, Greece; Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA FX Literary work of this article was in part funded by the Biomedical Research Foundation of the Academy of Athens, Athens, Greece, and the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, 20892, USA. NR 39 TC 21 Z9 22 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0014-2972 J9 EUR J CLIN INVEST JI Eur. J. Clin. Invest. PD OCT PY 2010 VL 40 IS 10 BP 932 EP 942 DI 10.1111/j.1365-2362.2010.02336.x PG 11 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 648QU UT WOS:000281709800009 PM 20649902 ER PT J AU Rouleau, JL Michler, RE Velazquez, EJ Oh, JK O'Connor, CM Desvigne-Nickens, P Sopko, G Lee, KL Jones, RH AF Rouleau, Jean L. Michler, Robert E. Velazquez, Eric J. Oh, Jae K. O'Connor, Christopher M. Desvigne-Nickens, Patrice Sopko, George Lee, Kerry L. Jones, Robert H. TI The STICH trial: evidence-based conclusions SO EUROPEAN JOURNAL OF HEART FAILURE LA English DT Editorial Material ID SURGICAL VENTRICULAR RESTORATION; CONGESTIVE-HEART-FAILURE; MYOCARDIAL-INFARCTION; RECONSTRUCTION; SURVIVAL; SURGERY; SHAPE C1 [Rouleau, Jean L.] Univ Montreal, Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada. [Michler, Robert E.] Albert Einstein Coll Med, Montefiore Med Ctr, New York, NY USA. [Velazquez, Eric J.; O'Connor, Christopher M.; Jones, Robert H.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. [Oh, Jae K.] Mayo Clin, Rochester, MN USA. [Desvigne-Nickens, Patrice; Sopko, George; Lee, Kerry L.] NHLBI, NIH, Bethesda, MD 20892 USA. RP Rouleau, JL (reprint author), Univ Montreal, Montreal Heart Inst, 5000 Rue Belanger E, Montreal, PQ H1T 1C8, Canada. EM jean.rouleau@umontreal.ca NR 16 TC 8 Z9 10 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1388-9842 J9 EUR J HEART FAIL JI Eur. J. Heart Fail. PD OCT PY 2010 VL 12 IS 10 BP 1028 EP 1030 DI 10.1093/eurjhf/hfq140 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 654MI UT WOS:000282172000007 PM 20861132 ER PT J AU FitzGerald, LM McDonnell, SK Carlson, EE Langeberg, W McIntosh, LM Deutsch, K Ostrander, EA Schaid, DJ Stanford, JL AF FitzGerald, Liesel M. McDonnell, Shannon K. Carlson, Erin E. Langeberg, Wendy McIntosh, Laura M. Deutsch, Kerry Ostrander, Elaine A. Schaid, Daniel J. Stanford, Janet L. TI Genome-wide linkage analyses of hereditary prostate cancer families with colon cancer provide further evidence for a susceptibility locus on 15q11-q14 SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Article DE prostate cancer; colon cancer; linkage analysis; pleiotropic effects; hereditary ID COLORECTAL-CANCER; BREAST-CANCER; INTERNATIONAL CONSORTIUM; SUGGESTIVE EVIDENCE; GENETIC-LINKAGE; CHROMOSOME 1P36; SCAN; RISK; ASSOCIATION; AGGRESSIVENESS AB The search for susceptibility loci in hereditary prostate cancer (HPC) is challenging because of locus and disease heterogeneity. One approach to reduce disease heterogeneity is to stratify families on the basis of the occurrence of multiple cancer types. This method may increase the power for detecting susceptibility loci, including those with pleiotropic effects. We have completed a genome-wide SNP linkage analysis of 96 HPC families, each of which has one or more first-degree relatives with colon cancer (CCa), and further analyzed the subset of families with two or more CCa cases (n=27). When only a prostate cancer (PCa) phenotype was considered to be affected, we observed suggestive evidence for linkage (LOD >= 1.86) at 15q14, 18q21 and 19q13 in all families, and at 1p32 and 15q11-q14 in families with two or more CCa cases. When both the PCa and CCa phenotypes were considered affected, suggestive evidence for linkage was observed at 11q25, 15q14 and 18q21 in all families, and at 1q31, 11q14 and 15q11-14 in families with two or more CCa cases. The strongest linkage signal was identified at 15q14 when both PCa and CCa phenotypes were considered to be affected in families with two or more CCa cases (recessive HLOD=3.88). These results provide further support for the presence of HPC susceptibility loci on chromosomes 11q14, 15q11-q14 and 19q13 and highlight loci at 1q31, 11q, 15q11-14 and 18q21 as having possible pleiotropic effects. This study shows the benefit of using a comprehensive family cancer history to create more genetically homogenous subsets of HPC families for linkage analyses. European Journal of Human Genetics (2010) 18, 1141-1147; doi: 10.1038/ejhg.2010.49; published online 21 April 2010 C1 [FitzGerald, Liesel M.; Langeberg, Wendy; McIntosh, Laura M.; Stanford, Janet L.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA. [McDonnell, Shannon K.; Carlson, Erin E.; Schaid, Daniel J.] Mayo Clin, Div Biostat, Rochester, MN USA. [Ostrander, Elaine A.] Inst Syst Biol, Seattle, WA USA. [Ostrander, Elaine A.] NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. [Stanford, Janet L.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. RP Stanford, JL (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, M4-B874,POB 19024, Seattle, WA 98109 USA. EM jstanfor@fhcrc.org OI Ostrander, Elaine/0000-0001-6075-9738 FU National Cancer Institute [RO1-CA080122, P50-CA097186]; Fred Hutchinson Cancer Research Center FX We thank all the men and women who are participating in the PROGRESS study for their time, effort and cooperation. We also thank the study staff for help with ongoing data collection and processing. This work was supported by grants RO1-CA080122 and P50-CA097186 from the National Cancer Institute, with additional support from the Fred Hutchinson Cancer Research Center. Genotyping services were provided by the Center for Inherited Disease Research at Johns Hopkins University (contract N01-HG-65403 from the National Institutes of Health). We acknowledge the Prostate Cancer Foundation and the Intramural Program of the National Human Genome Research Institute. NR 57 TC 5 Z9 5 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1018-4813 J9 EUR J HUM GENET JI Eur. J. Hum. Genet. PD OCT PY 2010 VL 18 IS 10 BP 1141 EP 1147 DI 10.1038/ejhg.2010.49 PG 7 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 653KI UT WOS:000282089600012 PM 20407467 ER PT J AU Cai, Y Xiong, K Zhang, XM Cai, HB Luo, XG Feng, JC Clough, RW Struble, RG Patrylo, PR Chu, YP Kordower, JH Yan, XX AF Cai, Yan Xiong, Kun Zhang, Xue-Mei Cai, Huaibin Luo, Xue-Gang Feng, Jia-Chun Clough, Richard W. Struble, Robert G. Patrylo, Peter R. Chu, Yaping Kordower, Jeffrey H. Yan, Xiao-Xin TI beta-Secretase-1 elevation in aged monkey and Alzheimer's disease human cerebral cortex occurs around the vasculature in partnership with multisystem axon terminal pathogenesis and beta-amyloid accumulation SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE aging; dementia; hypometabolism; neuritic plaque; neuroplasticity; non-human primate ID MILD COGNITIVE IMPAIRMENT; A-BETA; CEREBROSPINAL-FLUID; PLAQUE PATHOGENESIS; DYSTROPHIC NEURITES; SECRETASE BACE1; TRANSGENIC MICE; RHESUS-MONKEYS; BRAIN; PROTEIN AB Alzheimer's disease (AD) is the most common dementia-causing disorder in the elderly; it may be related to multiple risk factors, and is characterized pathologically by cerebral hypometabolism, paravascular beta-amyloid peptide (A beta) plaques, neuritic dystrophy, and intra-neuronal aggregation of phosphorylated tau. To explore potential pathogenic links among some of these lesions, we examined beta-secretase-1 (BACE1) alterations relative to A beta deposition, neuritic pathology and vascular organization in aged monkey and AD human cerebral cortex. Western blot analyses detected increased levels of BACE1 protein and beta-site-cleavage amyloid precursor protein C-terminal fragments in plaque-bearing human and monkey cortex relative to controls. In immunohistochemistry, locally elevated BACE1 immunoreactivity (IR) occurred in AD but not in control human cortex, with a trend for increased overall density among cases with greater plaque pathology. In double-labeling preparations, BACE1 IR colocalized with immunolabeling for A beta but not for phosphorylated tau. In perfusion-fixed monkey cortex, locally increased BACE1 IR co-existed with intra-axonal and extracellular A beta IR among virtually all neuritic plaques, ranging from primitive to typical cored forms. This BACE1 labeling localized to swollen/sprouting axon terminals that might co-express one or another neuronal phenotype markers (GABAergic, glutamatergic, cholinergic, or catecholaminergic). Importantly, these BACE1-labeled dystrophic axons resided near to or in direct contact with blood vessels. These findings suggest that plaque formation in AD or normal aged primates relates to a multisystem axonal pathogenesis that occurs in partnership with a potential vascular or metabolic deficit. The data provide a mechanistic explanation for why senile plaques are present preferentially near the cerebral vasculature. C1 [Zhang, Xue-Mei; Clough, Richard W.; Patrylo, Peter R.; Yan, Xiao-Xin] So Illinois Univ, Sch Med Carbondale, Dept Anat, Carbondale, IL 62901 USA. [Cai, Yan; Xiong, Kun; Luo, Xue-Gang] Cent S Univ, Xiangya Med Sch, Dept Anat & Neurobiol, Changsha, Hunan, Peoples R China. [Cai, Yan; Patrylo, Peter R.] So Illinois Univ, Sch Med, Dept Physiol, Carbondale, IL 62901 USA. [Zhang, Xue-Mei; Feng, Jia-Chun] Jilin Univ, Hosp 1, Dept Neurol, Changchun 130023, Jilin, Peoples R China. [Cai, Huaibin] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Struble, Robert G.] So Illinois Univ, Sch Med, Ctr Alzheimers Dis, Carbondale, IL 62901 USA. [Chu, Yaping; Kordower, Jeffrey H.] Rush Univ, Med Ctr, Dept Neurol Sci, Chicago, IL 60612 USA. RP Yan, XX (reprint author), So Illinois Univ, Sch Med Carbondale, Dept Anat, 1135 Lincoln Dr,2069 Life Sci 3, Carbondale, IL 62901 USA. EM xyan@siumed.edu RI Cai, Huaibin/H-3359-2013 OI Cai, Huaibin/0000-0002-8596-6108 FU Illinois Department of Public Health; National Institute of Health [1R21NS056371]; Southern Illinois University Center for Alzheimer's disease and related disorders; National Institute on Aging FX This study was supported in part by the Illinois Department of Public Health (X. X. Yan), the National Institute of Health (1R21NS056371 to P. R. Patrylo and X. X. Yan), the Southern Illinois University Center for Alzheimer's disease and related disorders (X. X. Yan, P. R. Patrylo, and R. G. Struble), and the intramural program of the National Institute on Aging (H. Cai). We thank Elan Pharmaceuticals and Haruhiko Akiyama and Peter Davis for providing A beta and p-Tau (PHF1) antibodies. NR 58 TC 29 Z9 30 U1 0 U2 9 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD OCT PY 2010 VL 32 IS 7 BP 1223 EP 1238 DI 10.1111/j.1460-9568.2010.07376.x PG 16 WC Neurosciences SC Neurosciences & Neurology GA 659NG UT WOS:000282572700018 PM 20726888 ER PT J AU Kimura, Y Simeon, FG Hatazawa, J Mozley, PD Pike, VW Innis, RB Fujita, M AF Kimura, Yasuyuki Simeon, Fabrice G. Hatazawa, Jun Mozley, P. David Pike, Victor W. Innis, Robert B. Fujita, Masahiro TI Biodistribution and radiation dosimetry of a positron emission tomographic ligand, F-18-SP203, to image metabotropic glutamate subtype 5 receptors in humans SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING LA English DT Article DE mGluR5; PET; Dosimetry; Defluorination ID HUMAN PET; RADIOLIGAND; BRAIN; GLUTATHIONE; C-11-ABP688; RAT AB A new PET ligand, 3-fluoro-5-(2-(2-F-18-(fluoromethyl)-thiazol-4-yl)ethynyl)benzonitrile (F-18-SP203), is a positron emission tomographic radioligand selective for metabotropic glutamate subtype 5 receptors. The purposes of this study were to estimate the radiation-absorbed doses of F-18-SP203 in humans and to determine from the distribution of radioactivity in bone structures with various proportions of bone and red marrow whether F-18-SP203 undergoes defluorination. Whole-body images were acquired for 5 h after injecting F-18-SP203 in seven healthy humans. Urine was collected at various time points. Radiation-absorbed doses were estimated by the Medical Internal Radiation Dose scheme. After injecting F-18-SP203, the two organs with highest radiation exposure were urinary bladder wall and gallbladder wall, consistent with both urinary and fecal excretion. In the skeleton, most of the radioactivity was in bone structures that contain red marrow and not in those without red marrow. Although the dose to red marrow (30.9 mu Sv/MBq) was unusually high, the effective dose (17.8 mu Sv/MBq) of F-18-SP203 was typical of that of other F-18 radiotracers. F-18-SP203 causes an effective dose in humans typical of several other F-18 radioligands and undergoes little defluorination. C1 [Kimura, Yasuyuki; Simeon, Fabrice G.; Pike, Victor W.; Innis, Robert B.; Fujita, Masahiro] NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA. [Hatazawa, Jun] Osaka Univ, Grad Sch Med, Dept Nucl Med & Tracer Kinet, Osaka, Japan. [Mozley, P. David] Merck Res Labs, West Point, PA USA. RP Fujita, M (reprint author), NIMH, Mol Imaging Branch, 10 Ctr Dr, Bethesda, MD 20892 USA. EM fujitam@mail.nih.gov RI Kimura, Yasuyuki/D-4459-2016 OI Kimura, Yasuyuki/0000-0002-7927-9483 FU National Institute of Mental Health [Z01-MH-002795-07, Z01-MH-002852-04] FX This research was supported by the Intramural Program of the National Institute of Mental Health (projects Z01-MH-002795-07 and Z01-MH-002852-04). We thank Leah P. Dickstein, Maria D. Ferraris Araneta, Gerald L. Hodges, Nobuyo Kimura, Barbara Scepura, Cheryl Wallisch, Yi Zhang, Jeih-San Liow, Robert L. Gladding, Amira K. Brown, and the staff of the PET Department for successful completion of the studies; and Dr. Michael G. Stabin for his suggestions concerning the data analysis; and PMOD Technologies (Zurich, Switzerland) for providing its image analysis and modeling software. NR 25 TC 21 Z9 21 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1619-7070 J9 EUR J NUCL MED MOL I JI Eur. J. Nucl. Med. Mol. Imaging PD OCT PY 2010 VL 37 IS 10 BP 1943 EP 1949 DI 10.1007/s00259-010-1447-8 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 647DX UT WOS:000281597700017 PM 20585776 ER PT J AU Anderson, AL Harris, TB Houston, DK Tylavsky, FA Lee, JS Sellmeyer, DE Sahyoun, NR AF Anderson, Amy L. Harris, Tamara B. Houston, Denise K. Tylavsky, Frances A. Lee, Jung Sun Sellmeyer, Deborah E. Sahyoun, Nadine R. TI Relationships of dietary patterns with body composition in older adults differ by gender and PPAR-gamma Pro12Ala genotype SO EUROPEAN JOURNAL OF NUTRITION LA English DT Article DE Diet; Dietary patterns; Body composition; Older adults; PPAR-gamma Pro12Ala genotype ID ACTIVATED RECEPTOR-GAMMA-2 GENE; TYPE-2 DIABETES-MELLITUS; PRO 12ALA POLYMORPHISM; MASS INDEX; PPAR-GAMMA-2 GENE; WAIST CIRCUMFERENCE; FAT DISTRIBUTION; INSULIN SENSITIVITY; RISK-FACTORS; OBESITY AB Dietary patterns may better capture the multifaceted effects of diet on body composition than individual nutrients or foods. The objective of this study was to investigate the dietary patterns of a cohort of older adults, and examine relationships of dietary patterns with body composition. The influence of a polymorphism in the peroxisome proliferator-activated receptor-gamma (PPAR-gamma) gene was considered. The Health, Aging and Body Composition (Health ABC) Study is a prospective cohort study of 3,075 older adults. Participants' body composition and genetic variation were measured in detail. Food intake was assessed with a semi-quantitative food frequency questionnaire (Block Dietary Data Systems, Berkeley, CA), and dietary patterns of 1,809 participants with complete data were derived by cluster analysis. Six clusters were identified, including a 'Healthy foods' cluster characterized by higher intake of low-fat dairy products, fruit, whole grains, poultry, fish and vegetables. An interaction was found between dietary patterns and PPAR-gamma Pro12Ala genotype in relation to body composition. While Pro/Pro homozygous men and women in the 'Healthy foods' cluster did not differ significantly in body composition from those in other clusters, men with the Ala allele in the 'Healthy foods' cluster had significantly lower levels of adiposity than those in other clusters. Women with the Ala allele in the 'Healthy foods' cluster differed only in right thigh intermuscular fat from those in other clusters. Relationships between diet and body composition in older adults may differ by gender and by genetic factors such as PPAR-gamma Pro12Ala genotype. C1 [Anderson, Amy L.; Sahyoun, Nadine R.] Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. [Harris, Tamara B.] NIA, NIH, Bethesda, MD 20892 USA. [Houston, Denise K.] Wake Forest Univ, Sticht Ctr Aging, Winston Salem, NC 27157 USA. [Tylavsky, Frances A.] Univ Tennessee, Dept Prevent Med, Memphis, TN 38103 USA. [Lee, Jung Sun] Univ Georgia, Dept Foods & Nutr, Athens, GA 30602 USA. [Sellmeyer, Deborah E.] Univ Calif San Francisco, Div Endocrinol, San Francisco, CA 94115 USA. RP Anderson, AL (reprint author), Univ Maryland, Dept Nutr & Food Sci, 0112 Skinner Bldg, College Pk, MD 20742 USA. EM amylouiseanderson@yahoo.com FU National Institute on Aging [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106]; NIH, National Institute on Aging FX ALA, NRS and TBH were responsible for the study concept and research design. ALA and NRS drafted the article. DKH, FAT, JSL, DES and TBH critically reviewed the article and contributed important intellectual content. National Institute on Aging contracts N01-AG-6-2101, N01-AG-6-2103, and N01-AG-6-2106. This research was supported in part by the Intramural Research Program of the NIH, National Institute on Aging. NR 47 TC 14 Z9 16 U1 0 U2 4 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1436-6207 J9 EUR J NUTR JI Eur. J. Nutr. PD OCT PY 2010 VL 49 IS 7 BP 385 EP 394 DI 10.1007/s00394-010-0096-9 PG 10 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 654ON UT WOS:000282177900001 PM 20174813 ER PT J AU Kalra, A Garde, S Hummer, G AF Kalra, A. Garde, S. Hummer, G. TI Lubrication by molecularly thin water films confined between nanostructured membranes SO EUROPEAN PHYSICAL JOURNAL-SPECIAL TOPICS LA English DT Article ID BOUNDARY LUBRICATION; LAYERING TRANSITIONS; SUBNANOMETER FILMS; CARBON NANOTUBE; LIQUID-FILMS; DYNAMICS; FLUIDITY; SURFACES; DEPENDENCE; SIMULATION AB We use molecular dynamics simulations to study thermal sliding of two nanostructured surfaces separated by nanoscale water films. We find that friction at molecular separations is determined primarily by the effective free energy landscape for motion in the plane of sliding, which depends sensitively on the surface character and the molecular structure of the confined water. Small changes in the surface nanostructure can have dramatic effects on the apparent rheology. Whereas porous and molecularly rough interfaces of open carbon nanotube membranes are found to glide with little friction, a comparably smooth interface of end-capped nanotubes is effectively stuck. The addition of salt to the water layer is found to reduce the sliding friction. Surprisingly, the intervening layers of water remain fluid in all cases, even in the case of high apparent friction between the two membranes. C1 [Kalra, A.; Garde, S.] Rensselaer Polytech Inst, Howard P Isermann Dept Chem & Biol Engn, Troy, NY 12180 USA. [Kalra, A.; Hummer, G.] NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Kalra, A (reprint author), Shell Oil Co, Houston, TX 77252 USA. EM gardes@rpi.edu; gerhard.hummer@nih.gov RI Garde, Shekhar/C-3060-2008; Hummer, Gerhard/A-2546-2013 OI Hummer, Gerhard/0000-0001-7768-746X FU National Science Foundation NSEC [DMR 0642573]; NIH, NIDDK FX G.H. thanks Prof. J. C. Rasaiah for many stimulating discussions. S.G. was supported partially by the National Science Foundation NSEC grant (DMR 0642573). G.H. was supported by the Intramural Research Program of the NIH, NIDDK. NR 34 TC 9 Z9 9 U1 2 U2 25 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1951-6355 J9 EUR PHYS J-SPEC TOP JI Eur. Phys. J.-Spec. Top. PD OCT PY 2010 VL 189 IS 1 BP 147 EP 154 DI 10.1140/epjst/e2010-01317-9 PG 8 WC Physics, Multidisciplinary SC Physics GA 678SQ UT WOS:000284101100012 ER PT J AU Huijben, S Nelson, WA Wargo, AR Sim, DG Drew, DR Read, AF AF Huijben, Silvie Nelson, William A. Wargo, Andrew R. Sim, Derek G. Drew, Damien R. Read, Andrew F. TI CHEMOTHERAPY, WITHIN-HOST ECOLOGY AND THE FITNESS OF DRUG-RESISTANT MALARIA PARASITES SO EVOLUTION LA English DT Article DE Competitive release; Plasmodium chabaudi; selection coefficient; transmission; within-host fitness ID PLASMODIUM-FALCIPARUM MALARIA; MIXED-GENOTYPE INFECTIONS; REVERSE-TRANSCRIPTION PCR; ANTIMALARIAL RESISTANCE; GAMETOCYTE PRODUCTION; COMPETITIVE RELEASE; CHABAUDI INFECTIONS; PLUS PYRIMETHAMINE; GENETIC DIVERSITY; SEX-RATIO AB A major determinant of the rate at which drug-resistant malaria parasites spread through a population is the ecology of resistant and sensitive parasites sharing the same host. Drug treatment can significantly alter this ecology by removing the drug-sensitive parasites, leading to competitive release of resistant parasites. Here, we test the hypothesis that the spread of resistance can be slowed by reducing drug treatment and hence restricting competitive release. Using the rodent malaria model Plasmodium chabaudi, we found that low-dose chemotherapy did reduce competitive release. A higher drug dose regimen exerted stronger positive selection on resistant parasites for no detectable clinical gain. We estimated instantaneous selection coefficients throughout the course of replicate infections to analyze the temporal pattern of the strength and direction of within-host selection. The strength of selection on resistance varied through the course of infections, even in untreated infections, but increased immediately following drug treatment, particularly in the high-dose groups. Resistance remained under positive selection for much longer than expected from the half life of the drug. Although there are many differences between mice and people, our data do raise the question whether the aggressive treatment regimens aimed at complete parasite clearance are the best resistance-management strategies for humans. C1 [Huijben, Silvie; Sim, Derek G.; Read, Andrew F.] Penn State Univ, Ctr Infect Dis Dynam, Dept Biochem, University Pk, PA 16827 USA. [Huijben, Silvie; Sim, Derek G.; Read, Andrew F.] Penn State Univ, Dept Entomol, University Pk, PA 16827 USA. [Huijben, Silvie; Wargo, Andrew R.; Sim, Derek G.; Drew, Damien R.; Read, Andrew F.] Univ Edinburgh, Sch Biol Sci, Edinburgh EH9 3JT, Midlothian, Scotland. [Nelson, William A.] Queens Univ, Dept Biol, Kingston, ON K7L 3N6, Canada. [Wargo, Andrew R.] Univ Washington, Dept Biol, Seattle, WA 98195 USA. [Drew, Damien R.] Walter & Eliza Hall Inst Med Res Biotechnol Ctr, Bundoora, Vic 3086, Australia. [Read, Andrew F.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Huijben, S (reprint author), Penn State Univ, Ctr Infect Dis Dynam, Dept Biochem, University Pk, PA 16827 USA. EM suh18@psu.edu RI Nelson, William/D-1405-2013 FU Darwin Trust of the University of Edinburgh; National Institute of General Medical Sciences [R01GM089932] FX We thank the Darwin Trust of the University of Edinburgh for supporting SH, the Wellcome Trust for supporting the experiments reported here, the BBSRC for supporting the development of the quantitative strain-specific gametocyte protocols, T. Day and the Banff International Research Station for Mathematical Innovation and Discovery for getting AR and WN talking, K. Paaijmans and two anonymous reviewers for comments on the MS, and A. Bell, V. Barclay, B. Chan, J. de Roode, and E. Levri and members of the RAPIDD program of the Science & Technology Directorate, Department of Homeland Security, and the Fogarty International Center, National Institutes of Health for stimulating discussion. MS completion was supported by Award Number R01GM089932 from the National Institute of General Medical Sciences. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of General Medical Sciences or the National Institutes of Health. NR 84 TC 35 Z9 35 U1 6 U2 22 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0014-3820 J9 EVOLUTION JI Evolution PD OCT PY 2010 VL 64 IS 10 BP 2952 EP 2968 DI 10.1111/j.1558-5646.2010.01068.x PG 17 WC Ecology; Evolutionary Biology; Genetics & Heredity SC Environmental Sciences & Ecology; Evolutionary Biology; Genetics & Heredity GA 659NN UT WOS:000282573800011 PM 20584075 ER PT J AU Jumpertz, R Wiesner, T Bluher, M Engeli, S Batkai, S Wirtz, H Bosse-Henck, A Stumvoll, M AF Jumpertz, R. Wiesner, T. Blueher, M. Engeli, S. Batkai, S. Wirtz, H. Bosse-Henck, A. Stumvoll, M. TI Circulating Endocannabinoids and N-acyl-ethanolamides in Patients with Sleep Apnea - Specific Role of Oleoylethanolamide SO EXPERIMENTAL AND CLINICAL ENDOCRINOLOGY & DIABETES LA English DT Article DE endocannabinoids; oleoylethanolamide; anandamide; 2-arachidonyl-glycerol; sleep apnea ID ADIPOSE-TISSUE; ENERGY-BALANCE; SYSTEM; ANANDAMIDE; OBESITY; METABOLISM; ACTIVATION; DYSREGULATION; ADIPOCYTES; BRAIN AB Objective: The endocannabinoid system promotes diverse effects on fat and glucose metabolism as well as on energy balance and sleep regulation. The role of N-acylethanolamides like oleoylethanolamide (OEA) and other endo-cannabinoids such as anandamide (AEA) and 2-arachidonyl-glycerol (2-AG) has not yet been investigated in patients with sleep apnea. Design and Methods: We measured circulating OEA, AEA and 2-AG in patients with sleep apnea (n = 20) and healthy control subjects (n = 57). Respiratory distress index (RDI) as measured by polysomnography was used as a quantitative index of sleep apnea. Results: In patients with sleep apnea OEA serum concentrations were significantly higher than in control subjects (8.4 pmol/ml (95 % CI 6.9;9.9) vs. 4.0 (3.5;4.5); p < 0.0001, adjusted for body mass index (BMI), fasting insulin, HDL and LDL cholesterol). In contrast, AEA (2.9 (95 % CI 1.9;3.9) vs. 1.8 (1.4;2.1), p = 0.09) and 2-AG (20.0 (-14.5;54.5) vs. 32.8 (21.4;44.2), p = 0.56) were not significantly different between patients with sleep apnea and control subjects after adjustment. In the sleep apnea group, OEA serum concentrations were associated with RDI (r(2) = 0.28, p = 0.02) and BMI (r(2) = 0.32, p = 0.01). However, OEA was not associated with BMI in the control group (p = 0.10). Conclusions: These results indicate that among the three analyzed fatty acid derivatives, OEA plays a specific role in patients with sleep apnea. Together with animal data, the 2-fold elevation of OEA serum concentrations could be interpreted as a neuroprotective mechanism against chronic oxidative stressors and a mechanism to promote wakefulness in patients with nocturnal sleep deprivation and daytime hypersomnolence. C1 [Jumpertz, R.; Wiesner, T.; Blueher, M.; Wirtz, H.; Bosse-Henck, A.; Stumvoll, M.] Univ Leipzig, Dept Internal Med, D-04103 Leipzig, Germany. [Engeli, S.; Batkai, S.] Hannover Med Sch, Inst Clin Pharmacol, D-3000 Hannover, Germany. [Batkai, S.] NIAAA, NIH, Bethesda, MD USA. RP Stumvoll, M (reprint author), Univ Leipzig, Dept Internal Med, Liebigstr 18, D-04103 Leipzig, Germany. EM michael.stumvoll@medizin.uni-leipzig.de RI Batkai, Sandor/G-3889-2010; Batkai, Sandor/H-7983-2014 FU DFG (Deutsche Forschungsgemeinschaft) [KFO 152] FX This study was supported by the DFG (Deutsche Forschungsgemeinschaft; KFO 152). NR 30 TC 9 Z9 9 U1 0 U2 1 PU JOHANN AMBROSIUS BARTH VERLAG MEDIZINVERLAGE HEIDELBERG GMBH PI STUTTGART PA RUEDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0947-7349 J9 EXP CLIN ENDOCR DIAB JI Exp. Clin. Endocrinol. Diabet. PD OCT PY 2010 VL 118 IS 9 BP 591 EP 595 DI 10.1055/s-0030-1253344 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 664WB UT WOS:000282992900004 PM 20429051 ER PT J AU Thorsell, A AF Thorsell, Annika TI Brain neuropeptide Y and corticotropin-releasing hormone in mediating stress and anxiety SO EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Article; Proceedings Paper CT Annual FASEB Experimental Biology Meeting CY APR 21, 2009 CL San Diego, CA DE neuropeptide Y; corticotropin-releasing hormone; anxiety; stress ID FACTOR RECEPTOR-1 ANTAGONIST; FEAR-POTENTIATED STARTLE; ANXIOLYTIC-LIKE ACTION; PARAVENTRICULAR NUCLEUS; BASOLATERAL AMYGDALA; RESTRAINT STRESS; MESSENGER-RNAS; CONFLICT TEST; ANTISENSE OLIGODEOXYNUCLEOTIDES; PANCREATIC-POLYPEPTIDE AB Neuropeptides such as neuropeptide Y (NPY) and corticotropin-releasing hormone (CRH) have been implicated not only in acute regulation of stress/anxiety-related behaviors, but adaptations and changes in these neuropeptide systems may also participate in the regulation of behavior and endocrine responses during chronic stress. NPY is an endogenous anxiolytic neuropeptide, while CRH has anxiogenic properties upon central administration. Changes in these neuropeptide systems may contribute to disease states and give us indications for putative treatment targets for stress/anxiety disorders as well as alcohol/drug dependence. In this review, we briefly present these two systems and review their involvement in mediating the responses to acute and chronic stressors, as well as their possible roles in the development and progression of stress/anxiety disorders. We suggest that neuropeptides may be attractive in treatment development for stress/anxiety disorders, as well as for alcohol/drug dependence, based on their specificity and activity following exposure to external challenges, i.e. stressors, and their differential adaptations during transition from an acute to a chronic stress exposure state. C1 NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD 20892 USA. RP Thorsell, A (reprint author), NIAAA, Lab Clin & Translat Studies, NIH, 10 Ctr Dr,10 CRC-1E-5330, Bethesda, MD 20892 USA. EM thorsella@mail.nih.gov OI Thorsell, Annika/0000-0003-3535-3845 NR 90 TC 42 Z9 42 U1 1 U2 5 PU SOC EXPERIMENTAL BIOLOGY MEDICINE PI MAYWOOD PA 195 WEST SPRING VALLEY AVE, MAYWOOD, NJ 07607-1727 USA SN 1535-3702 J9 EXP BIOL MED JI Exp. Biol. Med. PD OCT PY 2010 VL 235 IS 10 BP 1163 EP 1167 DI 10.1258/ebm.2010.009331 PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 670VN UT WOS:000283455500004 PM 20881320 ER PT J AU Katz, SI AF Katz, Stephen I. TI The current status of investigative dermatology II SO EXPERIMENTAL DERMATOLOGY LA English DT Editorial Material C1 NIAMSD, NIH, Bethesda, MD 20892 USA. RP Katz, SI (reprint author), NIAMSD, NIH, Bethesda, MD 20892 USA. EM katzs@mail.nih.gov NR 1 TC 2 Z9 2 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0906-6705 J9 EXP DERMATOL JI Exp. Dermatol. PD OCT PY 2010 VL 19 IS 10 BP 857 EP 859 DI 10.1111/j.1600-0625.2010.01178.x PG 3 WC Dermatology SC Dermatology GA 651TB UT WOS:000281948900002 PM 20872993 ER PT J AU Foki, T Pirker, W Klinger, N Geissler, A Rath, J Steinkellner, T Hoellinger, I Gruber, S Haubenberger, D Lehrner, J Pusswald, G Trattnig, S Auff, E Beisteiner, R AF Foki, T. Pirker, W. Klinger, N. Geissler, A. Rath, J. Steinkellner, T. Hoellinger, I. Gruber, S. Haubenberger, D. Lehrner, J. Pusswald, G. Trattnig, S. Auff, E. Beisteiner, R. TI FMRI correlates of apraxia in Parkinson's disease patients OFF medication SO EXPERIMENTAL NEUROLOGY LA English DT Article DE fMRI; Parkinson's disease; Apraxia; Impaired dexterity; Coin rotation ID LIMB-KINETIC APRAXIA; MILD COGNITIVE IMPAIRMENT; FIELD BOLD-FMRI; CORTICOBASAL DEGENERATION; MIRROR MOVEMENTS; LESIONS; DEXTERITY; LEVODOPA; GESTURES; LANGUAGE AB Impairment of hand dexterity in Parkinson's disease (PD) is usually attributed to bradykinesia. Recently, behavioral studies illustrated that decreased dexterity might also be due to limb-kinetic apraxia (LkA), as demonstrated by impaired performance in a coin rotation task. Here, we provide a first investigation on whether functional magnetic resonance imaging (fMRI) may reveal specific brain activation patterns for PD patients with impaired performance in a coin rotation task. We compared coin rotation as an apraxia task to simple finger tapping as a bradykinesia task in ten PD patients OFF medication and matched healthy controls. In addition to a tendency for general overactivation, PD patients showed a perirolandic dissociation with precentral overactivation and postcentral underactivation. This finding significantly separated PD patients from healthy controls. (C) 2010 Elsevier Inc. All rights reserved. C1 [Beisteiner, R.] Med Univ Vienna, Study Grp Clin fMRI, Dept Neurol, MR Ctr Excellence, A-1090 Vienna, Austria. [Trattnig, S.] Med Univ Vienna, Dept Radiol, A-1090 Vienna, Austria. [Haubenberger, D.] NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Beisteiner, R (reprint author), Med Univ Vienna, Study Grp Clin fMRI, Dept Neurol, MR Ctr Excellence, Wahringer Gurtel 18-20, A-1090 Vienna, Austria. EM thomas.foki@meduniwien.ac.at; walter.pirker@meduniwien.ac.at; nicolaus.klinger@meduniwien.ac.at; alexander.geissler@meduniwien.ac.at; jakob.rath@meduniwien.ac.at; tomsteinkellner@hotmail.com; ilse.hoellinger@meduniwien.ac.at; n0543161@students.meduniwien.ac.at; dietrich.haubenberger@meduniwien.ac.at; johann.lehrner@meduniwien.ac.at; Gisela.pusswald@meduniwien.ac.at; siegfried.trattnig@meduniwien.ac.at; eduard.auff@meduniwien.ac.at; roland.beisteiner@meduniwien.ac.at OI Lehrner, Johann/0000-0001-8270-9272 FU Austrian Science Fund [P18057]; Department of Neurology, Medical University of Vienna, Austria FX The study was supported by the Austrian Science Fund (P18057) and the Department of Neurology, Medical University of Vienna, Austria. There was no other sponsor or funding organization. The funding sources did not have any particular role in the study design; the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. NR 44 TC 9 Z9 9 U1 0 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD OCT PY 2010 VL 225 IS 2 BP 416 EP 422 DI 10.1016/j.expneurol.2010.07.019 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 654SV UT WOS:000282191500022 PM 20659452 ER PT J AU Hyun, DH Mughal, MR Yang, H Lee, JH Ko, EJ Hunt, ND de Cabo, R Mattson, MP AF Hyun, Dong-Hoon Mughal, Mohamed R. Yang, Hyunwon Lee, Ji Hyun Ko, Eun Joo Hunt, Nicole D. de Cabo, Rafael Mattson, Mark P. TI The plasma membrane redox system is impaired by amyloid beta-peptide and in the hippocampus and cerebral cortex of 3xTgAD mice SO EXPERIMENTAL NEUROLOGY LA English DT Article DE Alzheimer's disease; Plasma membrane redox system; Oxidative stress; Coenzyme Q; Amyloid beta-peptide ID TRANSGENIC MOUSE MODEL; ALZHEIMERS-DISEASE; LIPID-PEROXIDATION; OXIDATIVE STRESS; A-BETA; CALORIC RESTRICTION; BEHAVIORAL DEFICITS; HYDROGEN-PEROXIDE; RAT-LIVER; IN-VITRO AB Membrane-associated oxidative stress has been implicated in the synaptic dysfunction and neuronal degeneration that occurs in Alzheimer's disease (AD), but the underlying mechanisms are unknown. Enzymes of the plasma membrane redox system (PMRS) provide electrons for energy metabolism and recycling of antioxidants. Here, we show that activities of several PMRS enzymes are selectively decreased in plasma membranes from the hippocampus and cerebral cortex of 3xTgAD mice, an animal model of AD. Our results that indicate the decreased PMRS enzyme activities are associated with decreased levels of coenzyme Q(10) and increased levels of oxidative stress markers. Neurons overexpressing the PMRS enzymes (NQO1 or cytochrome b5 reductase) exhibit increased resistance to amyloid beta-peptide (A beta). If and to what extent A beta is the cause of the impaired PMRS enzymes in the 3xTgAD mice is unknown. Because these mice also express mutant tau and presenilin-1, it is possible that one or more of the PMRS could be adversely affected by these mutations. Nevertheless, the results of our cell culture studies clearly show that exposure of neurons to A beta 1-42 is sufficient to impair PMRS enzymes. The impairment of the PMRS in an animal model of AD, and the ability of PMRS enzyme activities to protect neurons against A beta-toxicity, suggest enhancement PMRS function as a novel approach for protecting neurons against oxidative damage in AD and related disorders. (C) 2010 Elsevier Inc. All rights reserved. C1 [Hyun, Dong-Hoon; Lee, Ji Hyun; Ko, Eun Joo] Ewha Womans Univ, Dept Life Sci, Div Life & Pharmaceut Sci, Seoul 120750, South Korea. [Hyun, Dong-Hoon; Mughal, Mohamed R.; Mattson, Mark P.] NIA, Neurosci Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Yang, Hyunwon] Seoul Womens Univ, Div Environm & Life Sci, Seoul 139774, South Korea. [Hunt, Nicole D.; de Cabo, Rafael] NIA, Lab Expt Gerontol, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Mattson, Mark P.] Johns Hopkins Univ, Dept Neurosci, Sch Med, Baltimore, MD 21205 USA. RP Hyun, DH (reprint author), Ewha Womans Univ, Dept Life Sci, Div Life & Pharmaceut Sci, Seoul 120750, South Korea. EM hyundh@ewha.ac.kr RI Mattson, Mark/F-6038-2012; de Cabo, Rafael/J-5230-2016 OI de Cabo, Rafael/0000-0002-3354-2442 FU National Institute on Aging, National Institutes of Health, USA; Ewha Womans University, South Korea FX We thank Jose Manuel Villalba (Universidad de Cordoba, Spain) and David Ross (University of Colorado at Denver. USA) for providing antibodies against b5R and NQO1, respectively. We thank Alan Sartorelli (Yale University School of Medicine, USA) for giving pBE8 and pCB6 plasmid vectors. This research was supported by the Intramural Research Program of the National Institute on Aging, National Institutes of Health, USA, and by the Ewha Womans University Research Grant of 2007, South Korea. NR 53 TC 22 Z9 22 U1 0 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD OCT PY 2010 VL 225 IS 2 BP 423 EP 429 DI 10.1016/j.expneurol.2010.07.020 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 654SV UT WOS:000282191500023 PM 20673763 ER PT J AU Bates, AH Mu, JB Jiang, HY Fairhurst, RM Su, XZ AF Bates, Adam H. Mu, Jianbing Jiang, Hongying Fairhurst, Rick M. Su, Xin-zhuan TI Use of magnetically purified Plasmodium falciparum parasites improves the accuracy of erythrocyte invasion assays SO EXPERIMENTAL PARASITOLOGY LA English DT Article DE Plasmodium falciparum; Parasite purification; Erythrocyte invasion; Magnetic column ID PURIFICATION; DISRUPTION; SEPARATION; MALARIA; PATHWAY; STAGE; BLOOD AB Merozoite invasion of erythrocytes is a crucial step for the asexual cycle of Plasmodium falciparum. Multiple invasion pathways, which involve different ligand-receptor interactions, have been identified in P. falciparum by examining the entry of purified parasite into erythrocytes with different surface receptors, either mutant or under different enzyme treatments. The most critical step for a successful invasion assay is the isolation of erythrocytes infected with viable schizonts. Here, we applied a magnetic column to purify the schizonts for the erythrocyte invasion assay. Comparing to Percoll-sorbitol purification method, this modified approach showed great improvement on reproducibility and reliability of invasion assay, particularly for short-term, culture-adapted parasite isolates. The magnetic purification method is an excellent alternative for parasite isolates that do not tolerate or with unknown sensitivity to Percoll-sorbitol exposure. Published by Elsevier Inc. C1 [Bates, Adam H.; Mu, Jianbing; Jiang, Hongying; Fairhurst, Rick M.; Su, Xin-zhuan] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. RP Mu, JB (reprint author), Natl Inst Hlth, Lab Malaria & Vector Res, 12735 Twinbrook Pkwy,Room 3E-32C, Rockville, MD 20852 USA. EM jmu@niaid.nih.gov OI Su, Xinzhuan/0000-0003-3246-3248 FU Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health FX This study was supported by the Intramural Research Program of the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. We thank Dr. Deepak Gaur for advice on invasion assays. NR 12 TC 4 Z9 4 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 0014-4894 J9 EXP PARASITOL JI Exp. Parasitol. PD OCT PY 2010 VL 126 IS 2 BP 278 EP 280 DI 10.1016/j.exppara.2010.05.007 PG 3 WC Parasitology SC Parasitology GA 638HX UT WOS:000280885500029 PM 20493844 ER PT J AU Duffy, A Greten, T AF Duffy, Austin Greten, Tim TI Developing better treatments in hepatocellular carcinoma SO EXPERT REVIEW OF GASTROENTEROLOGY & HEPATOLOGY LA English DT Article DE cirrhosis; hepatocellular carcinoma; sorafenib; targeted therapy; translational; trial design ID ENDOTHELIAL GROWTH-FACTOR; RANDOMIZED CONTROLLED-TRIAL; PHASE-II TRIAL; PLUS OXALIPLATIN GEMOX; COMBINATION CHEMOTHERAPY; INCREASED EXPRESSION; ANTITUMOR-ACTIVITY; TUMOR PROGRESSION; TARGETED THERAPY; 1ST-LINE THERAPY AB The marked heterogeneity of hepatocellular carcinoma (HCC), particularly with regard to the etiology and severity of the underlying cirrhosis, makes clinical trial design in this disease very challenging. In addition, despite the global burden of HCC, there have been relatively few randomized studies. The major advance in medical therapy in HCC has been the benefit of sorafenib, as demonstrated in two Phase III studies. However, the benefit is small, and new therapies to augment or replace sorafenib are urgently needed. These newer therapies, as well as the progress made in two important areas - clinical trial design and molecular characterization - are the subject of this article. C1 [Duffy, Austin; Greten, Tim] NCI, Med Oncol Branch, Bethesda, MD 20892 USA. RP Greten, T (reprint author), NCI, Med Oncol Branch, 9000 Rockville Pike,10-13N240G, Bethesda, MD 20892 USA. RI Greten, Tim/B-3127-2015 OI Greten, Tim/0000-0002-0806-2535 FU NIH, National Cancer Institute, Center for Cancer Research FX The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products or organizations imply endorsement by the US Government. This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 80 TC 13 Z9 14 U1 0 U2 0 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1747-4124 EI 1747-4132 J9 EXPERT REV GASTROENT JI Expert Rev. Gastroenterol. Hepatol. PD OCT PY 2010 VL 4 IS 5 BP 551 EP 560 DI 10.1586/EGH.10.58 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 860YF UT WOS:000297983700010 PM 20932140 ER PT J AU Lee, CR Imig, JD Edin, ML Foley, J DeGraff, LM Bradbury, JA Graves, JP Lih, FB Clark, J Myers, P Perrow, AL Lepp, AN Kannon, MA Ronnekleiv, OK Alkayed, NJ Falck, JR Tomer, KB Zeldin, DC AF Lee, Craig R. Imig, John D. Edin, Matthew L. Foley, Julie DeGraff, Laura M. Bradbury, J. Alyce Graves, Joan P. Lih, Fred B. Clark, James Myers, Page Perrow, A. Ligon Lepp, Adrienne N. Kannon, M. Alison Ronnekleiv, Oline K. Alkayed, Nabil J. Falck, John R. Tomer, Kenneth B. Zeldin, Darryl C. TI Endothelial expression of human cytochrome P450 epoxygenases lowers blood pressure and attenuates hypertension-induced renal injury in mice SO FASEB JOURNAL LA English DT Article DE CYP2J2; CYP2C8; epoxygenase; EETs; transgenic ID SOLUBLE EPOXIDE HYDROLASE; SALT-SENSITIVE HYPERTENSION; ARACHIDONIC-ACID METABOLISM; ANGIOTENSIN-II; NITRIC-OXIDE; EPOXYEICOSATRIENOIC ACIDS; HYPERPOLARIZING FACTORS; CORONARY-ARTERIES; MOLECULAR-CLONING; GENE-EXPRESSION AB Renal cytochrome P450 (CYP)-derived epoxyeicosatrienoic acids (EETs) regulate sodium transport and blood pressure. Although endothelial CYP-derived EETs are potent vasodilators, their contribution to the regulation of blood pressure remains unclear. Consequently, we developed transgenic mice with endothelial expression of the human CYP2J2 and CYP2C8 epoxygenases to increase endothelial EET biosynthesis. Compared to wild-type littermate controls, an attenuated afferent arteriole constrictor response to endothelin-1 and enhanced dilator response to acetylcholine was observed in CYP2J2 and CYP2C8 transgenic mice. CYP2J2 and CYP2C8 transgenic mice demonstrated modestly, but not significantly, lower mean arterial pressure under basal conditions compared to wild-type controls. However, mean arterial pressure was significantly lower in both CYP2J2 and CYP2C8 transgenic mice during coadministration of N-nitro-L-arginine methyl ester and indomethacin. In a separate experiment, a high-salt diet and subcutaneous angiotensin II was administered over 4 wk. The angiotensin/high-saltinduced increase in systolic blood pressure, proteinuria, and glomerular injury was significantly attenuated in CYP2J2 and CYP2C8 transgenic mice compared to wild-type controls. Collectively, these data demonstrate that increased endothelial CYP epoxygenase expression attenuates afferent arteriolar constrictor reactivity and hypertension-induced increases in blood pressure and renal injury in mice. We conclude that endothelial CYP epoxygenase function contributes to the regulation of blood pressure.-Lee, C. R., Imig, J. D., Edin, M. E., Foley, J., DeGraff, L. M., Bradbury, J. A., Graves, J. P., Lih, F. B., Clark, J., Myers, P., Perrow, A. L., Lepp, A. N., Kannon, M. A., Ronnekleiv, O. K., Alkayed, N. J., Falck, J. R., Tomer, K. B., Zeldin, D. C. Endothelial expression of human cytochrome P450 epoxygenases lowers blood pressure and attenuates hypertension-induced renal injury in mice. FASEB J. 24, 3770-3781 (2010). www.fasebj.org C1 [Lee, Craig R.; Edin, Matthew L.; Foley, Julie; DeGraff, Laura M.; Bradbury, J. Alyce; Graves, Joan P.; Lih, Fred B.; Clark, James; Myers, Page; Perrow, A. Ligon; Tomer, Kenneth B.; Zeldin, Darryl C.] NIEHS, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA. [Lee, Craig R.; Kannon, M. Alison] Univ N Carolina, Div Pharmacotherapy & Expt Therapeut, Eshelman Sch Pharm, Chapel Hill, NC USA. [Imig, John D.; Lepp, Adrienne N.] Med Coll Wisconsin, Dept Physiol, Milwaukee, WI 53226 USA. [Ronnekleiv, Oline K.; Alkayed, Nabil J.] Oregon Hlth & Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97201 USA. [Alkayed, Nabil J.] Oregon Hlth & Sci Univ, Dept Anesthesiol & Perioperat Med, Portland, OR 97201 USA. [Falck, John R.] Univ Texas SW Med Ctr Dallas, Dept Biochem, Dallas, TX 75390 USA. RP Zeldin, DC (reprint author), NIEHS, Div Intramural Res, NIH, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM zeldin@niehs.nih.gov RI Tomer, Kenneth/E-8018-2013; OI Imig, John/0000-0002-9668-2899; Falck, John/0000-0002-9219-7845; Edin, Matthew/0000-0002-7042-500X; Lee, Craig/0000-0003-3595-5301 FU American Heart Association; U.S. National Institutes of Health (NIH) [DK38826]; Advancing a Healthier Wisconsin; Robert A. Welch Foundation; NIH [P01 NS049210, GM31278]; NIH, National Institute of Environmental Health Sciences (NIEHS) [Z01 ES050167, Z01 ES025034] FX The authors gratefully acknowledge the technical assistance of Dr. Taiping Jia in completion of the in situ hybridization studies, and Drs. Anton Jetten and Robert Langenbach for their helpful comments during the preparation of this manuscript. This publication was made possible by a Beginning Grant-in-Aid from the American Heart Association to C.R.L.; U.S. National Institutes of Health (NIH) grant DK38826 and an Advancing a Healthier Wisconsin grant to J.D.I.; NIH grant P01 NS049210 to O.K.R. and N.J.A.; NIH grant GM31278 and support from the Robert A. Welch Foundation to J.R.F., and funds from the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (NIEHS) to K.B.T. (Z01 ES050167) and D.C.Z. (Z01 ES025034). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIEHS or NIH. D.C.Z. is a coinventor on U.S. Patent 6,531,506 B1 (issued March 11, 2003), Inhibition of Epoxide Hydrolases for the Treatment of Hypertension, and on U.S. Patent 6,916,843 B1 (issued July 12, 2005), Anti-inflammatory Actions of Cytochrome P450 Epoxygenase-Derived Eicosanoids. J.D.I. is a coinventor on U.S. Patent 7,550,617 (issued June 23, 2009), Compositions and Methods for the Treatment of Renal and Cardiovascular Disease. No other authors have conflicts of interest to disclose. NR 53 TC 76 Z9 76 U1 0 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD OCT PY 2010 VL 24 IS 10 BP 3770 EP 3781 DI 10.1096/fj.10-160119 PG 12 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 690LI UT WOS:000285005900016 PM 20495177 ER PT J AU Elson, AET Dotson, CD Egan, JM Munger, SD AF Elson, Amanda E. T. Dotson, Cedrick D. Egan, Josephine M. Munger, Steven D. TI Glucagon signaling modulates sweet taste responsiveness SO FASEB JOURNAL LA English DT Article DE proglucagon; glucagon receptor; gustation; 7B2; behavior ID VASOACTIVE-INTESTINAL-PEPTIDE; RECEPTOR-CELLS; GUSTATORY RESPONSIVENESS; PROHORMONE CONVERTASE-2; COEXPRESSION PATTERNS; BITTER TASTE; ALPHA-CELLS; NULL MICE; RAT; BUDS AB The gustatory system provides critical information about the quality and nutritional value of food before it is ingested. Thus, physiological mechanisms that modulate taste function in the context of nutritional needs or metabolic status could optimize ingestive decisions. We report that glucagon, which plays important roles in the maintenance of glucose homeostasis, enhances sweet taste responsiveness through local actions in the mouse gustatory epithelium. Using immunohistochemistry and confocal microscopy, we found that glucagon and its receptor (GlucR) are coexpressed in a subset of mouse taste receptor cells. Most of these cells also express the T1R3 taste receptor implicated in sweet and/or umami taste. Genetic or pharmacological disruption of glucagon signaling in behaving mice indicated a critical role for glucagon in the modulation of taste responsiveness. Scg5(-/-) mice, which lack mature glucagon, had significantly reduced responsiveness to sucrose as compared to wild-type littermates in brief-access taste tests. No significant differences were seen in responses to prototypical salty, sour, or bitter stimuli. Taste responsiveness to sucrose was similarly reduced upon acute and local disruption of glucagon signaling by the GlucR antagonist L-168,049. Together, these data indicate a role for local glucagon signaling in the peripheral modulation of sweet taste responsiveness.-Elson, A.E.T., Dotson, C.D., Egan, J.M., Munger, S.D. Glucagon signaling modulates sweet taste responsiveness. FASEB J. 24, 3960-3969 (2010). www.fasebj.org C1 [Elson, Amanda E. T.; Dotson, Cedrick D.; Munger, Steven D.] Univ Maryland, Sch Med, Dept Anat & Neurobiol, Baltimore, MD 21201 USA. [Egan, Josephine M.] NIA, NIH, Baltimore, MD 21224 USA. RP Munger, SD (reprint author), Univ Maryland, Sch Med, Dept Anat & Neurobiol, 20 S Penn St,Rm S251, Baltimore, MD 21201 USA. EM smung001@umaryland.edu OI Elson, Amanda/0000-0002-5744-5954 FU National Institute on Deafness and Communication Disorders [DC010110, DC010113]; Ajinomoto Amino Acid Research Program; National Institute on Aging FX The authors thank Iris Lindberg (University of Maryland School of Medicine) and the S.D.M. laboratory for helpful comments on the manuscript, and Iris Lindberg, Maureen Charron (Albert Einstein School of Medicine, New York, NY, USA), and Charles Zuker (Columbia University, New York, NY, USA) for generous gifts of reagents. This work was supported by the National Institute on Deafness and Communication Disorders (DC010110, S. D. M.; DC010113, A.E.T.E.), the Ajinomoto Amino Acid Research Program (S.D.M.) and the National Institute on Aging Intramural Program (J.M.E.). NR 60 TC 33 Z9 34 U1 1 U2 8 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD OCT PY 2010 VL 24 IS 10 BP 3960 EP 3969 DI 10.1096/fj.10-158105 PG 10 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 690LI UT WOS:000285005900033 PM 20547661 ER PT J AU Neumann, S Geras-Raaka, E Marcus-Samuels, B Gershengorn, MC AF Neumann, Susanne Geras-Raaka, Elizabeth Marcus-Samuels, Bernice Gershengorn, Marvin C. TI Persistent cAMP signaling by thyrotropin (TSH) receptors is not dependent on internalization SO FASEB JOURNAL LA English DT Article DE G-protein-coupled receptors; receptor-mediated endocytosis; sustained signaling; beta-arrestin-2; dynamin ID HORMONE RECEPTOR; ENDOCYTOSIS; DYNAMIN; ALPHA AB Evidence was presented that thyrotropin [thyroid-stimulating hormone (TSH)]-stimulated persistent cAMP signaling is dependent on receptor (with G-protein alpha subunits and adenylyl cyclase) internalization. Because it is not clear whether G proteins and adenylyl cyclase internalize with receptors, we tested whether persistent cAMP signaling by TSH receptor (TSHR) is dependent on internalization. We measured persistent TSHR signaling as an accumulation of cAMP in HEK-EM293 cells permanently expressing human TSHRs incubated with isobutylmethylxanthine for 30 min after washing the cells to remove unbound TSH, and TSHR internalization by fluorescence microscopy using Alexa-tagged TSH and binding assays using (125)I-TSH. TSHRs, but not the closely related lutropin or follitropin receptors, exhibit persistent cAMP signaling. TSHRs were not internalized by 30 min incubation with unlabeled TSH; however, expression of beta-arrestin-2 promoted TSHR internalization that was inhibited by dynasore, a dynamin inhibitor. Expression of beta-arrestin-2 had no effect on TSHR cAMP signaling, dynasore inhibited TSHR cAMP signaling in the absence or presence of TSHR internalization, and expression of a dominant-negative mutant dynamin, which inhibited internalization, had no effect on persistent cAMP signaling. Persistent cAMP signaling was specifically inhibited by a small molecule TSHR antagonist. We conclude that TSHRs do not have to be internalized to exhibit persistent cAMP signaling.-Neumann, S., Geras-Raaka, E., Marcus-Samuels, B., Gershengorn, M. C. Persistent cAMP signaling by thyrotropin (TSH) receptors is not dependent on internalization. FASEB J. 24, 3992-3999 (2010). www.fasebj.org C1 [Neumann, Susanne; Geras-Raaka, Elizabeth; Marcus-Samuels, Bernice; Gershengorn, Marvin C.] NIDDK, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Gershengorn, MC (reprint author), NIDDK, Clin Endocrinol Branch, NIH, 50 South Dr, Bethesda, MD 20892 USA. EM marving@intra.niddk.nih.gov FU U.S. National Institutes of Health [1 Z01 DK011006] FX This research was supported by the Intramural Research Program of the U.S. National Institutes of Health (1 Z01 DK011006). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 18 TC 12 Z9 12 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD OCT PY 2010 VL 24 IS 10 BP 3992 EP 3999 DI 10.1096/fj.10-161745 PG 8 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 690LI UT WOS:000285005900036 PM 20538910 ER PT J AU Cruse, G Kaur, D Leyland, M Bradding, P AF Cruse, Glenn Kaur, Davinder Leyland, Mark Bradding, Peter TI A novel Fc epsilon RI beta-chain truncation regulates human mast cell proliferation and survival SO FASEB JOURNAL LA English DT Article DE MS4A2; IgE receptor; cell cycle; G2 phase; cell membrane ID AFFINITY IGE RECEPTOR; B-LYMPHOCYTES; ACTIVATION; CD20; IDENTIFICATION; EXPRESSION; SUBUNIT; HTM4; PROGRESSION; TRYPTASE AB Mast cells contribute to allergy through IgE-dependent activation via the high-affinity IgE receptor Fc epsilon RI. The role of the Fc epsilon RI beta chain (MS4A2) in mast cell function is not understood fully, although it serves to amplify Fc epsilon RI-dependent signaling. We demonstrate the expression of a novel MS4A2 truncation lacking exon 3 in human mast cells termed MS4A2(trunc). MS4A2(trunc) gene expression was regulated negatively by the mast cell growth factor stem cell factor (SCF), and its expression was not detected in the SCF receptor gain-of-function human mast cell line HMC-1. Unlike MS4A2, MS4A2(trunc) did not traffic to the cytoplasmic membrane but instead was associated with the nuclear membrane. Overexpression of MS4A2(trunc) induced human lung mast cell death and profoundly inhibited HMC-1 cell proliferation by inducing G(2)-phase cell cycle arrest and apoptosis. Thus, we have identified a novel splice variant of MS4A2 that might be important in the regulation of human mast cell proliferation and survival. This finding demonstrates that the MS4A2 gene has multiple roles, extending beyond the regulation of acute allergic responses. By understanding the mechanisms regulating its function, it might be possible to induce its expression in mast cells in vivo, which could lead to better treatments for diseases such as mastocytosis and asthma.-Cruse, G., Kaur, D., Leyland, M., Bradding, P. A novel Fc epsilon RI beta-chain truncation regulates human mast cell proliferation and survival. FASEB J. 24, 4047-4057 (2010). www.fasebj.org C1 [Leyland, Mark] Univ Leicester, Dept Biochem, Leicester LE1 7RH, Leics, England. [Cruse, Glenn; Kaur, Davinder; Bradding, Peter] Glenfield Gen Hosp, Inst Lung Hlth, Dept Infect Immun & Inflammat, Glenfield, England. RP Cruse, G (reprint author), NIAID, Lab Allerg Dis, NIH, Bldg 10,Rm 11C205,10 Ctr Dr,MSC 1881, Bethesda, MD 20892 USA. EM glenncruse@hotmail.com RI Cruse, Glenn/B-4597-2012 FU Novartis Pharmaceuticals FX This study was funded in part by an unrestricted Ph.D. studentship (G.C.) from Novartis Pharmaceuticals. The authors are grateful to the Midlands Lung Tissue Consortium for the coordination of human lung tissue retrieval. The authors also thank Ryan Murray-Slater and Michelle Powell for assistance with the mast cell isolation and the Wolfson Foundation Light Microscopy Facility (Department of Biochemistry, University of Leicester) for the use of the scanning confocal microscope. NR 42 TC 15 Z9 17 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD OCT PY 2010 VL 24 IS 10 BP 4047 EP 4057 DI 10.1096/fj.10-158378 PG 11 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 690LI UT WOS:000285005900040 PM 20554927 ER PT J AU Gemmill, JAL Stratton, P Cleary, SD Ballweg, ML Sinaii, N AF Gemmill, Julie Anne L. Stratton, Pamela Cleary, Sean D. Ballweg, Mary Lou Sinaii, Ninet TI Cancers, infections, and endocrine diseases in women with endometriosis SO FERTILITY AND STERILITY LA English DT Article DE Cancer; infectious disease; endocrine disease; endometriosis ID HOSPITAL DISCHARGE DIAGNOSIS; OVARIAN-CANCER; MEDICAL CONDITIONS; BREAST-CANCER; RISK; HISTORY; POLYMORPHISM; SUSCEPTIBILITY; INFERTILITY; MELANOMA AB Objective: To assess the prevalence of patient-reported, physician-diagnosed comorbid conditions in women with endometriosis. Design: Cross-sectional study of self-reported survey data. Setting: Academic research. Patient(s): Four thousand three hundred thirty-one Endometriosis Association (EA) members reporting surgically diagnosed endometriosis. Intervention(s): None. Main Outcome Measure(s): Self-reported, physician-diagnosed infectious diseases, cancers, and endocrine diseases. Result(s): Nearly two-thirds of women reported one or more of the assessed conditions. Recurrent upper respiratory infections and recurrent vaginal infections were common and more likely in women responding to the EA survey. Melanoma was reported by 0.7% (n = 29), breast cancer by 0.4% (n = 16), and ovarian cancer by 0.2% (n = 10). While ovarian cancer and melanoma were significantly more common than in the general population, breast cancer was surprisingly less common. Addison's disease and Cushing's syndrome were rare (0.2% and 0.1%, respectively). Conclusion(s): Respondents reported a higher prevalence of recurrent upper respiratory or vaginal infections, melanoma, and ovarian cancer than the general population. These findings document other potential associations related to the immune system, which may help focus future research into this disease. (Fertil Steril (R) 2010;94:1627-31. (C) 2010 by American Society for Reproductive Medicine.) C1 [Sinaii, Ninet] NIH, Biostat & Clin Epidemiol Serv, Ctr Clin, Bethesda, MD 20891 USA. [Gemmill, Julie Anne L.; Stratton, Pamela; Sinaii, Ninet] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod Endocrinol, NIH, Bethesda, MD USA. [Cleary, Sean D.] George Washington Univ, Dept Epidemiol & Biostat, Sch Publ Hlth & Hlth Serv, Washington, DC USA. [Ballweg, Mary Lou] Endometriosis Assoc Int Headquarters, Milwaukee, WI USA. RP Sinaii, N (reprint author), NIH, Biostat & Clin Epidemiol Serv, Ctr Clin, 10 Ctr Dr,Bldg 10,Room 2N-228, Bethesda, MD 20891 USA. EM sinaiin@mail.nih.gov FU Zeneca Pharmaceuticals; Eunice Kennedy Shriver National Institute of Child Health and Human Development; Clinical Center, National Institute of Health, Bethesda, Maryland; Endometriosis Association, International Headquarters, Milwaukee, Wisconsin; Endometriosis Association FX The 1998 Endometriosis Association Survey was supported by an unrestricted educational grant from Zeneca Pharmaceuticals. The research for this study was supported by the Intramural Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Clinical Center, National Institute of Health, Bethesda, Maryland, and the Endometriosis Association, International Headquarters, Milwaukee, Wisconsin.; The authors thank the Endometriosis Association for supporting the study and use of their 1998 survey data and the Eunice Kennedy Shriver National Institute of Child Health and Human Development Clinical Trials Database Team. They also thank Ms. Rebecca Greene, Ms. Nancy Kim, and Ms. Shannon Liu for entering the survey data and helping to prepare them for analysis. NR 29 TC 25 Z9 26 U1 1 U2 3 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 OCT PY 2010 VL 94 IS 5 BP 1627 EP 1631 DI 10.1016/j.fertnstert.2009.07.1698 PG 5 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 654IB UT WOS:000282160600011 PM 19945097 ER PT J AU Hubayter, ZR Popat, V Vanderhoof, VH Ndubizu, O Johnson, D Mao, E Calis, KA Troendle, JF Nelson, LM AF Hubayter, Ziad R. Popat, Vaishali Vanderhoof, Vien H. Ndubizu, Obioma Johnson, Diane Mao, Edie Calis, Karim A. Troendle, James F. Nelson, Lawrence M. TI A prospective evaluation of antral follicle function in women with 46,XX spontaneous primary ovarian insufficiency SO FERTILITY AND STERILITY LA English DT Article DE Primary ovarian insufficiency; hypergonadotropic hypogonadism; premature ovarian failure; premature menopause; lutienized Graafian follicle ID NORMAL MENSTRUAL-CYCLE; STIMULATING-HORMONE; HYPERGONADOTROPIC AMENORRHEA; GONADOTROPIN SUPPRESSION; OVULATION INDUCTION; CLINICAL-FEATURES; CONTROLLED-TRIAL; FAILURE; CELLS; ANDROSTENEDIONE AB Objective: To assess ovarian follicle function in women with 46,XX spontaneous primary ovarian insufficiency. Design: Case-control with nested prospective cohort. Setting: Clinical Research Center, National Institutes of Health. Patient(s): Women with primary ovarian insufficiency without estrogen replacement for 2 weeks (N = 97) and regularly menstruating control women (N = 42). Intervention(s): Single injection of 300 IU hrFSH. Main Outcome Measure(s): Change in serum estradiol at 24 hours. Result(s): Antral follicles >= 3 mm were detected in 73% (69/95) of patients; both serum estradiol and progesterone levels correlated significantly with maximum follicle diameter in these women. Patients with a maximum follicle diameter >= 8 mm had significantly higher serum estradiol and progesterone levels and significantly lower FSH and LH levels compared with patients without such follicles. In controls estradiol levels increased significantly after FSH administration, but in patients this was not the case despite the presence of an antral follicle >= 8 mm. Conclusion(s): Most women with 46, XX spontaneous primary ovarian insufficiency have antral follicles detectable by ultrasound, suggesting that down-regulation of FSH receptors is not the predominant mechanism of follicle dysfunction. Evidence of progesterone secretion by antral follicles >= 8 mm in these patients is consistent with prior histologic evidence that follicle luteinization is the predominant mechanism of follicle dysfunction in this condition. Prospective controlled investigation designed to improve ovulatory function and fertility in these women is indicated. (Fertil Steril (R) 2010;94:1769-74. (C)2010 by American Society for Reproductive Medicine.) C1 [Hubayter, Ziad R.; Popat, Vaishali; Vanderhoof, Vien H.; Ndubizu, Obioma; Nelson, Lawrence M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Integrat Reprod Med Unit, Intramural Res Program Reprod & Adult Endocrinol, Bethesda, MD 20892 USA. [Troendle, James F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biotatist & Bioinformat Branch, Bethesda, MD USA. [Johnson, Diane; Mao, Edie; Calis, Karim A.] NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Nelson, LM (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Integrat Reprod Med Unit, Intramural Res Program Reprod & Adult Endocrinol, CRC 1-3330,10 Ctr Dr,MSC 1103, Bethesda, MD 20892 USA. EM Lawrence_Nelson@nih.gov FU National Institute of Child Health and Human Development, National Institutes of Health FX Supported by the Intramural Research Program of the National Institute of Child Health and Human Development, National Institutes of Health. Vien H. Vanderhoof and Lawrence M. Nelson are Commissioned Officers in the United States Public Health Service. NR 40 TC 15 Z9 16 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 OCT PY 2010 VL 94 IS 5 BP 1769 EP 1774 DI 10.1016/j.fertnstert.2009.10.023 PG 6 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 654IB UT WOS:000282160600037 PM 19939372 ER PT J AU Brinton, LA Moghissi, KS Westhoff, CL Lamb, EJ Scoccia, B AF Brinton, Louise A. Moghissi, Kamran S. Westhoff, Carolyn L. Lamb, Emmet J. Scoccia, Bert TI Cancer risk among infertile women with androgen excess or menstrual disorders (including polycystic ovary syndrome) SO FERTILITY AND STERILITY LA English DT Article DE Androgen excess; PCOS; uterine cancer; breast cancer; ovarian cancer; risk ID OVULATION-STIMULATING DRUGS; STEIN-LEVENTHAL SYNDROME; TERM-FOLLOW-UP; ENDOMETRIAL CANCER; BREAST-CANCER; UNITED-STATES; CARCINOMA; ADENOCARCINOMA; ASSOCIATION; POPULATION AB Objective: To define relationships of androgen excesses to cancer risk. Design: Retrospective cohort study. Setting: Five large infertility practices. Patient(s): Among 12,193 women evaluated for infertility during 1965-1988 and traced for cancer incidence through 1999, 2,560 had androgen excess or menstrual disorders; among these, 412 met established criteria for polycystic ovary syndrome. Intervention(s): None. Main Outcome Measure(s): Cancer incidence. Derivation of standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) for cancer risk comparisons with the general population and rate ratios (RRs) for comparisons with other infertility patients. Result(s): Androgen excess/menstrual disorder patients showed significant SIRs for breast (1.31; 95% CI, 1.051.62) and uterine (2.02; 95% CI, 1.13-3.34) cancers and melanoma (1.96; 95% CI, 1.12-3.18). Significant associations for breast and uterine cancers were restricted to primary infertility patients (respective SIRs of 1.53 and 3.48). After adjustment for other cancer predictors, the only excess risk was for uterine cancer among primary infertility patients. Compared with women with secondary infertility and no androgen excess/menstrual disorder, those with primary infertility and a disorder had an RR of 1.88 (95% CI, 0.82-4.32). Cancer risks among the women with polycystic ovary syndrome or androgen excess disorders appeared to be similar to those in the more comprehensive group. Conclusion(s): Previous findings linking androgen excess disorders to elevated uterine cancer risks might largely reflect underlying risk profiles. (Fertil Steril (R) 2010;94:1787-92. (C)2010 by American Society for Reproductive Medicine.) C1 [Brinton, Louise A.] NCI, Rockville, MD USA. [Moghissi, Kamran S.] Wayne State Univ, Detroit, MI USA. [Westhoff, Carolyn L.] Columbia Univ, New York, NY USA. [Lamb, Emmet J.] Stanford Univ, Stanford, CA 94305 USA. [Scoccia, Bert] Univ Illinois, Chicago, IL USA. RP Brinton, LA (reprint author), 6120 Execut Blvd,Room 5018, Rockville, MD 20852 USA. EM brinton@nih.gov RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 FU National Cancer Institute, National Institutes of Health FX Supported by funds from the intramural research program of the National Cancer Institute, National Institutes of Health. NR 38 TC 10 Z9 10 U1 0 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 OCT PY 2010 VL 94 IS 5 BP 1787 EP 1792 DI 10.1016/j.fertnstert.2009.10.012 PG 6 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 654IB UT WOS:000282160600040 PM 19939368 ER PT J AU Patisaul, HB Jefferson, W AF Patisaul, Heather B. Jefferson, Wendy TI The pros and cons of phytoestrogens SO FRONTIERS IN NEUROENDOCRINOLOGY LA English DT Review DE Soy; Isoflavones; Genistein; Equol; Endocrine disruption; Estrogen; ER alpha; ER beta; Brain; Hypothalamus ID ESTROGEN-RECEPTOR-BETA; BREAST-CANCER RISK; ANTEROVENTRAL PERIVENTRICULAR NUCLEUS; SPRAGUE-DAWLEY RATS; GONADOTROPIN-RELEASING-HORMONE; SOY INFANT FORMULA; TESTICULAR DYSGENESIS SYNDROME; RANDOMIZED CONTROLLED-TRIAL; SEXUALLY DIMORPHIC NUCLEUS; DEPENDENT GENE-EXPRESSION AB Phytoestrogens are plant derived compounds found in a wide variety of foods, most notably soy. A litany of health benefits including a lowered risk of osteoporosis, heart disease, breast cancer, and menopausal symptoms, are frequently attributed to phytoestrogens but many are also considered endocrine disruptors, indicating that they have the potential to cause adverse health effects as well. Consequently, the question of whether or not phytoestrogens are beneficial or harmful to human health remains unresolved. The answer is likely complex and may depend on age, health status, and even the presence or absence of specific gut microflora. Clarity on this issue is needed because global consumption is rapidly increasing. Phytoestrogens are present in numerous dietary supplements and widely marketed as a natural alternative to estrogen replacement therapy. Soy infant formula now constitutes up to a third of the US market, and soy protein is now added to many processed foods. As weak estrogen agonists/antagonists with molecular and cellular properties similar to synthetic endocrine disruptors such as Bisphenol A (BPA), the phytoestrogens provide a useful model to comprehensively investigate the biological impact of endocrine disruptors in general. This review weighs the evidence for and against the purported health benefits and adverse effects of phytoestrogens. (C) 2010 Published by Elsevier Inc. C1 [Patisaul, Heather B.] N Carolina State Univ, Dept Biol, Raleigh, NC 27695 USA. NIEHS, Lab Reprod & Dev Toxicol, Res Triangle Pk, NC 27709 USA. RP Patisaul, HB (reprint author), N Carolina State Univ, Dept Biol, Raleigh, NC 27695 USA. EM heather_patisaul@ncsu.edu FU Intramural NIH HHS [Z99 ES999999] NR 303 TC 164 Z9 169 U1 13 U2 90 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-3022 J9 FRONT NEUROENDOCRIN JI Front. Neuroendocrinol. PD OCT PY 2010 VL 31 IS 4 SI SI BP 400 EP 419 DI 10.1016/j.yfrne.2010.03.003 PG 20 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 676EZ UT WOS:000283894200002 PM 20347861 ER PT J AU Mackenzie, GG Sun, Y Huang, LQ Xie, GA Ouyang, N Gupta, RC Johnson, F Komninou, D Kopelovich, L Rigas, B AF Mackenzie, Gerardo G. Sun, Yu Huang, Liqun Xie, Gang Ouyang, Nengtai Gupta, Ramesh C. Johnson, Francis Komninou, Despina Kopelovich, Levy Rigas, Basil TI Phospho-Sulindac (OXT-328), a Novel Sulindac Derivative, Is Safe and Effective in Colon Cancer Prevention in Mice SO GASTROENTEROLOGY LA English DT Article DE Colon Cancer; Phospho-Sulindac; Sulindac; Polyamines; Reactive Oxygen Species ID POLYAMINES; APOPTOSIS; INDUCTION; ASPIRIN; CELLS; TUMORIGENESIS; STRESS; GROWTH AB BACKGROUND & AIMS: Nonsteroidal anti-inflammatory drugs (NSAIDs) are effective cancer chemopreventive agents. However, chronic administration of NSAIDs is associated with significant side effects, mainly of the gastrointestinal tract. Given these limitations, we synthesized phospho-sulindac (P-S; OXT-328), a novel sulindac derivative. METHODS: Here, we evaluated the safety and efficacy of P-S in preclinical models, including its mechanism of action with human colon cancer cell (HCCC) lines and animal tumor models. RESULTS: (1) Compared with sulindac, P-S is much more potent in inhibiting the growth of cultured HCCCs and more efficacious in preventing the growth of HT-29 xenografts in nude mice. P-S also prevents the growth of intestinal tumors in Apc/Min mice. (2) In combination with difluoromethylornithine (DFMO), P-S reduced tumor multiplicity in Apc/Min mice by 90%. (3) P-S is much safer than sulindac as evidenced by its in vitro toxicologic evaluation and animal toxicity studies. Mechanistically, P-S increases the intracellular levels of reactive oxygen and nitrogen species, which are key early mediators of its chemopreventive effect. Moreover, P-S induces spermidine/ spermine N(1)-acetyltransferase enzymatic activity, and together with DFMO it reduces polyamine levels in vitro and in vivo. CONCLUSIONS: P-S displays considerable safety and efficacy, two pharmacologic properties that are essential for a potential cancer chemopreventive agent, and thus merits further evaluation. C1 [Rigas, Basil] SUNY Stony Brook, Canc Prevent Div, HSC, Dept Med, Stony Brook, NY 11794 USA. [Gupta, Ramesh C.; Johnson, Francis] Chem Master Int Inc, Stony Brook, NY USA. [Komninou, Despina] Medicon Inc, Stony Brook, NY USA. [Kopelovich, Levy] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. RP Rigas, B (reprint author), SUNY Stony Brook, Canc Prevent Div, HSC, Dept Med, T17-080 Stony Brook, Stony Brook, NY 11794 USA. EM basil.rigas@stonybrook.edu FU [R01-CA139453]; [N01-CN-43302 WA#7] FX This study was supported by grant R01-CA139453; N01-CN-43302 WA#7. NR 17 TC 34 Z9 34 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD OCT PY 2010 VL 139 IS 4 BP 1320 EP 1332 DI 10.1053/j.gastro.2010.06.044 PG 13 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 656WV UT WOS:000282372700042 PM 20600034 ER PT J AU Shebl, FM Maeder, D Shao, YW Prokunina-Olsson, L Schadt, EE O'Brien, TR AF Shebl, Fatma M. Maeder, Dennis Shao, Yongwu Prokunina-Olsson, Ludmila Schadt, Eric E. O'Brien, Thomas R. TI In the Absence of HCV Infection, Interferon Stimulated Gene Expression in Liver Is Not Associated With IL28B Genotype SO GASTROENTEROLOGY LA English DT Letter ID CHRONIC HEPATITIS-C; THERAPY C1 [Shebl, Fatma M.; Prokunina-Olsson, Ludmila] NCI, Div Canc Epidemiol & Genet, Natl Inst Hlth,Lab Translat Genom, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Maeder, Dennis] SAIC Frederick Inc, Adv Technol Program, Core Genotyping Facil, Frederick, MD USA. [Shao, Yongwu] Informat Management Serv Inc, Silver Spring, MD USA. [Schadt, Eric E.] Washington Pacific Biosci, Sage Bionetworks Seattle, Menlo Pk, CA USA. RP Shebl, FM (reprint author), NCI, Div Canc Epidemiol & Genet, Natl Inst Hlth,Lab Translat Genom, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. FU Intramural NIH HHS [, NIH0014113921]; PHS HHS [HHSN261200800001E, NIH0014113921] NR 7 TC 15 Z9 15 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD OCT PY 2010 VL 139 IS 4 BP 1422 EP 1424 DI 10.1053/j.gastro.2010.07.055 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 656WV UT WOS:000282372700050 PM 20800110 ER PT J AU Cotto, JH Davis, E Dowling, GJ Elcano, JC Staton, AB Weiss, SRB AF Cotto, Jessica H. Davis, Elisabeth Dowling, Gayathri J. Elcano, Jennifer C. Staton, Anna B. Weiss, Susan R. B. TI Gender Effects on Drug Use, Abuse, and Dependence: A Special Analysis of Results From the National Survey on Drug Use and Health SO GENDER MEDICINE LA English DT Article DE psychotherapeutics; gender differences; NSDUH; dependence; environmental risk; addiction ID MALE-FEMALE DIFFERENCES; EPIDEMIOLOGIC SURVEY; SUBSTANCE-ABUSE; SEX-DIFFERENCES; NONMEDICAL USE; USE DISORDERS; ALCOHOL; WOMEN; VULNERABILITY; COMORBIDITY AB Background: Gender is increasingly being studied for risk and protective factors underlying substance abuse and addiction. Objective: The aim of this study was to assess gender differences in rates of substance abuse and dependence among drug users. Methods: A national population sample was examined, focusing on 2 age groups (youths, aged 12-17 years, and young adults, aged 18-25 years) and several commonly abused substances (alcohol, marijuana, and nonmedical prescription medication use). Combined annual data from the National Survey on Drug Use and Health (NSDUH), aggregated from 200272005, were used for gender comparisons of rates of substance use, as well as abuse and dependence, among users. Results: Overall rates of substance use were significantly higher for males than for females (P < 0.01 for all substances except sedatives and tranquilizers); however, patterns of use, abuse, or dependence among users differed by age group and drug. Interestingly, patterns for youths differed from the overall population and from young adults. Girls exceeded boys in their use of alcohol (P < 0.01) and their nonmedical use of psychotherapeutics (ie, prescription-type pain relievers, stimulants, tranquilizers, sedatives) (P < 0.01); among users, girls were significantly more likely to be dependent on the latter (P < 0.01). Boys reported significantly greater use and abuse of and dependence on marijuana (P < 0.01). In the young adults, the proportion of female users reporting dependence on cocaine or psychotherapeutics was significantly higher than for male users (P < 0.01), who nonetheless reported significantly greater use of these drugs (P < 0.01). Among users, males generally exceeded females in meeting abuse criteria (P < 0.01 for marijuana among 12- to 17-year-olds and for alcohol, marijuana, and psychotherapeutics among 18- to 25-year-olds), with some exceptions mainly in the youngest cohort. Conclusions: In this national population sample of youths and young adults, these findings suggest that gender, age, and substance of abuse may all play a role in the observed patterns of drug use, abuse, and dependence. Understanding the reasons for these differences and continuing to evaluate these patterns over time could help in the development of targeted and more effective prevention and treatment interventions. (Gend Med. 2010;7:402-413) (C) 2010 Excerpta Medica Inc. C1 [Cotto, Jessica H.; Davis, Elisabeth; Dowling, Gayathri J.; Elcano, Jennifer C.; Staton, Anna B.; Weiss, Susan R. B.] NIDA, Bethesda, MD 20892 USA. RP Elcano, JC (reprint author), NIDA, 6001 Execut Blvd,Suite 5230, Bethesda, MD 20892 USA. EM elcanoj@nida.nih.gov NR 26 TC 58 Z9 59 U1 2 U2 16 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 1550-8579 J9 GENDER MED JI Gend. Med. PD OCT PY 2010 VL 7 IS 5 BP 402 EP 413 DI 10.1016/j.genm.2010.09.004 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 680SK UT WOS:000284254500003 PM 21056867 ER PT J AU Tsai, MJ Pan, HA Liou, DY Weng, CF Hoffer, BJ Cheng, H AF Tsai, M-J Pan, H-A Liou, D-Y Weng, C-F Hoffer, B. J. Cheng, H. TI Adenoviral gene transfer of bone morphogenetic protein-7 enhances functional recovery after sciatic nerve injury in rats SO GENE THERAPY LA English DT Article DE BMP7 gene therapy; peripheral nerve injury; neuroprotection; Schwann cell proliferation ID REMOTE VECTOR DELIVERY; PERIPHERAL-NERVE; SPINAL-CORD; SCHWANN-CELLS; PROSTACYCLIN SYNTHASE; NEUROTROPHIC FACTORS; SYMPATHETIC NEURONS; DENDRITIC GROWTH; IN-VIVO; REGENERATION AB Bone morphogenetic proteins (BMPs), members of the transforming growth factor-beta subfamily, function as instructive signals for neuronal lineage commitment and promote neuronal differentiation. However, the mechanism of BMP7 action in vivo after peripheral nerve injury is poorly understood. This study examines the efficacy of gene transfer of adenoviral (Ad) BMP7 on peripheral neuropathy. Transgene expression was found in both Ad-infected sciatic nerves and their respective remote neurons, indicating Ad transduction by a retrograde transport. After AdBMP7 infection to nerves, the sciatic nerves were crushed or transected. Hind limb functional behavior, including rotarod test and sciatic functional index, were conducted in rats weekly after nerve injury. Interestingly, enhanced BMP7 expression significantly improved hind limb functional recovery in AdBMP7-transduced rats when compared with AdGFP-transduced nerve-crushed or transected rats. Furthermore, AdBMP7 transduction reduced injury-induced macrophage activation, nerve demyelination and axonal degeneration. By contrast, AdBMP7 infection did not affect the hyperalgesia paw-withdrawal latency after nerve injury. We further examined the effect of AdBMP7 infection on sciatic nerve explant and Schwann cell cultures. Enhanced cell proliferation was significantly increased by AdBMP7 transduction in both cultures. Taken together, BMP7 overexpression by Ad gene transfer was beneficial in both nerves and Schwann cells on functional recovery after sciatic nerve injury in rats. Gene Therapy (2010) 17, 1214-1224; doi:10.1038/gt.2010.72; published online 3 June 2010 C1 [Tsai, M-J; Pan, H-A; Liou, D-Y; Cheng, H.] Taipei Vet Gen Hosp, Neurol Inst, Dept Neurosurg, Neural Regenerat Lab, Taipei 11217, Taiwan. [Tsai, M-J; Liou, D-Y; Cheng, H.] Taipei Vet Gen Hosp, Neurol Inst, Ctr Neural Regenerat, Taipei 11217, Taiwan. [Pan, H-A; Weng, C-F] Natl Dong Hwa Univ, Inst Biotechnol, Hualien 974, Taiwan. [Hoffer, B. J.] NIDA, NIH, Baltimore, MD USA. [Cheng, H.] Natl Yang Ming Univ, Dept Pharmacol, Sch Med, Taipei 112, Taiwan. [Cheng, H.] Natl Yang Ming Univ, Fac Med, Sch Med, Taipei 112, Taiwan. [Cheng, H.] Natl Yang Ming Univ, Inst Brain Sci, Sch Med, Taipei 112, Taiwan. RP Cheng, H (reprint author), Taipei Vet Gen Hosp, Neurol Inst, Dept Neurosurg, Neural Regenerat Lab, 322 Shih Pai Rd,Sec 2, Taipei 11217, Taiwan. EM cfweng@mail.ndhu.edu.tw; hc_cheng@vghtpe.gov.tw FU Republic of China (ROC) National Science Council [NSC96-2628-B-010-002-my3, NSC 97-3112-B-010-010]; Taipei Veterans General Hospital [V97S6-001, V98S6-001]; ROC Ministry of Education FX This work was supported by grants from the Republic of China (ROC) National Science Council (NSC96-2628-B-010-002-my3 and NSC 97-3112-B-010-010), from Taipei Veterans General Hospital (V97S6-001&V98S6-001) and a grant from the ROC Ministry of Education, Aim for the Top University Plan, Taiwan. We also acknowledge the excellent technical support of Ms Hsin-Chun Yang and Hsin-Jung Lee. NR 49 TC 10 Z9 11 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0969-7128 J9 GENE THER JI Gene Ther. PD OCT PY 2010 VL 17 IS 10 BP 1214 EP 1224 DI 10.1038/gt.2010.72 PG 11 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 664GO UT WOS:000282948600005 PM 20520648 ER PT J AU Zeng, XK Chauhan, C Hou, SX AF Zeng, Xiankun Chauhan, Chhavi Hou, Steven X. TI Characterization of Midgut Stem Cell- and Enteroblast-Specific Gal4 Lines in Drosophila SO GENESIS LA English DT Article DE Drosophila; intestinal stem cell; enteroblast; Gal4 lines ID BACTERIAL-INFECTION; NOTCH; PROLIFERATION; EXPRESSION; FATES AB The homeostasis of Drosophila midgut is maintained by multipotent intestinal stem cells (ISCs), each of which gives rise to a new ISC and an immature daughter cell, enteroblast (EB), after one asymmetric cell division. In Drosophila, the Gal4-UAS system is widely used to manipulate gene expression in a tissue-or cell-specific manner, but in Drosophila midgut, there are no ISC- or EB-specific Gal4 lines available. Here we report the generation and characterization of Dl-Gal4 and Su(H)GBE-Gal4 lines, which are expressed specifically in the ISCs and EBs separately. Additionally, we demonstrate that Dl-Gal4 and Su(H)GBE-Gal4 are expressed in adult midgut progenitors (AMPs) and niche peripheral cells (PCs) separately in larval midgut. These two Gal4 lines will serve as invaluable tools for navigating ISC behaviors. genesis 48:607-611,2010. dagger Published (C) 2010 Wiley-Liss, Inc. C1 [Zeng, Xiankun; Chauhan, Chhavi; Hou, Steven X.] Natl Canc Inst Frederick, Mouse Canc Genet Program, NIH, Frederick, MD USA. RP Zeng, XK (reprint author), Natl Canc Inst Frederick, Mouse Canc Genet Program, NIH, Frederick, MD USA. EM zengx2@mail.nih.gov RI Chauhan, Chhavi/A-9398-2011 FU National Institutes of Health, National Cancer Institute FX Contract grant sponsor: Intramural Research Program of the National Institutes of Health, National Cancer Institute NR 20 TC 43 Z9 43 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1526-954X J9 GENESIS JI Genesis PD OCT PY 2010 VL 48 IS 10 BP 607 EP 611 DI 10.1002/dvg.20661 PG 5 WC Developmental Biology; Genetics & Heredity SC Developmental Biology; Genetics & Heredity GA 671DE UT WOS:000283479400005 PM 20681020 ER PT J AU Klar, AJS AF Klar, Amar J. S. TI The Yeast Mating-Type Switching Mechanism: A Memoir SO GENETICS LA English DT Editorial Material ID HM-ALPHA LOCI; SACCHAROMYCES-CEREVISIAE; GENES; INTERCONVERSION; ALLELE AB It has been 33 years since I first presented results of genetic experiments that established the gene transposition model as the mechanism of mating-type switching in the budding yeast Saccharomyces cerevisiae at the Cold Spring Harbor Laboratory (CSHL) Yeast Genetics meeting in August 1977. Over two decades ago the Genetics Perspectives editors solicited a perspective on my participation in the studies that deciphered the mechanism of mating-type switching and revealed the phenomenon of gene silencing in yeast. Although flattered at the time, I thought that preparation of such an article called for a more seasoned researcher who had benefitted from seeing his contributions stand the test of time. Now realizing that our discovery of the transposition of a mutation from the HMa locus into the MAT (mating type) locus has provided the genetic evidence that established the gene transposition model, and having witnessed our conclusions confirmed by subsequent molecular studies, I decided that perhaps this is a good time to recount the chronology of events as they unfolded for me decades ago. C1 NCI, Dev Genet Sect, Gene Regulat & Chromosome Biol Lab, NIH, Frederick, MD 21702 USA. RP Klar, AJS (reprint author), NCI, Dev Genet Sect, Gene Regulat & Chromosome Biol Lab, NIH, Frederick, MD 21702 USA. EM klara@mail.nih.gov FU Intramural NIH HHS NR 21 TC 7 Z9 7 U1 1 U2 8 PU GENETICS SOC AM PI BETHESDA PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA SN 0016-6731 J9 GENETICS JI Genetics PD OCT PY 2010 VL 186 IS 2 BP 443 EP 449 DI 10.1534/genetics.110.122531 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 662KY UT WOS:000282807400001 PM 20940334 ER PT J AU Clayton, EW Smith, M Fullerton, SM Burke, W McCarty, CA Koenig, BA McGuire, AL Beskow, LM Dressler, L Lemke, AA Ramos, EM Rodriguez, LL AF Clayton, Ellen Wright Smith, Maureen Fullerton, Stephanie M. Burke, Wylie McCarty, Catherine A. Koenig, Barbara A. McGuire, Amy L. Beskow, Laura M. Dressler, Lynn Lemke, Amy A. Ramos, Erin M. Rodriguez, Laura Lyman CA EMERGE Consortium TI Confronting real time ethical, legal, and social issues in the Electronic Medical Records and Genomics (eMERGE) Consortium SO GENETICS IN MEDICINE LA English DT Editorial Material ID INTERNATIONAL HAPMAP PROJECT; GENETIC RESEARCH; INFORMED-CONSENT; COMMUNITY ENGAGEMENT; PARTICIPANTS; RECOMMENDATIONS; CONSULTATION; POPULATIONS; PROTECTION; LESSONS C1 [Clayton, Ellen Wright] Vanderbilt Univ, Ctr Biomed Eth & Soc, Nashville, TN 37203 USA. [Smith, Maureen; Lemke, Amy A.] Northwestern Univ, Feinberg Sch Med, NW Univ Clin & Translat Sci Inst, Ctr Genet Med, Chicago, IL 60611 USA. [Fullerton, Stephanie M.; Burke, Wylie] Univ Washington, Dept Bioeth & Humanities, Seattle, WA 98195 USA. [McCarty, Catherine A.] Marshfield Clin Res Fdn, Ctr Human Genet, Marshfield, WI USA. [Koenig, Barbara A.] Mayo Clin, Coll Med, Rochester, MN USA. [McGuire, Amy L.] Baylor Coll Med, Ctr Med Eth & Hlth Policy, Houston, TX 77030 USA. [Beskow, Laura M.] Duke Univ, Ctr Genome Eth Law & Policy, Duke Inst Genome Sci & Policy, Durham, NC USA. [Dressler, Lynn] Univ N Carolina, UNC Eshelman Sch Pharm, Inst Pharmacogen & Individualized Therapy, Chapel Hill, NC USA. [Ramos, Erin M.; Rodriguez, Laura Lyman] NHGRI, Bethesda, MD 20892 USA. RP Clayton, EW (reprint author), Vanderbilt Univ, Ctr Biomed Eth & Soc, 2525 W End Ave,Suite 400, Nashville, TN 37203 USA. EM ellen.clayton@vanderbilt.edu OI Clayton, Ellen/0000-0002-0308-4110; Fullerton, Stephanie/0000-0002-0938-6048 FU NHGRI NIH HHS [U01-HG-004608, U01 HG004599, U01 HG004608, U01 HG006375, U01HG004609, U01-HG-04599, U01 HG004603, U01 HG004609, U01-HG-004610, U01-HG-04603, U01 HG004610] NR 43 TC 30 Z9 30 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1098-3600 J9 GENET MED JI Genet. Med. PD OCT PY 2010 VL 12 IS 10 BP 616 EP 620 DI 10.1097/GIM.0b013e3181efdbd0 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 664HH UT WOS:000282950500003 PM 20733502 ER PT J AU Gitlin, JM Fischbeck, K Crawford, TO Cwik, V Fleischman, A Gonye, K Heine, D Hobby, K Kaufmann, P Keiles, S MacKenzie, A Musci, T Prior, T Lloyd-Puryear, M Sugarman, EA Terry, SF Urv, T Wang, C Watson, M Yaron, Y Frosst, P Howell, RR AF Gitlin, Jonathan M. Fischbeck, Kenneth Crawford, Thomas O. Cwik, Valerie Fleischman, Alan Gonye, Karla Heine, Deborah Hobby, Kenneth Kaufmann, Petra Keiles, Steven MacKenzie, Alex Musci, Thomas Prior, Thomas Lloyd-Puryear, Michele Sugarman, Elaine A. Terry, Sharon F. Urv, Tiina Wang, Ching Watson, Michael Yaron, Yuval Frosst, Phyllis Howell, R. Rodney TI Carrier testing for spinal muscular atrophy SO GENETICS IN MEDICINE LA English DT Editorial Material DE spinal muscular atrophy; carrier screening; national standards; policy; meeting report AB Spinal muscular atrophy is the most common fatal hereditary disease among newborns and infants. There is as yet no effective treatment. Although a carrier test is available, currently there is disagreement among professional medical societies who proffer standards of care as to whether or not carrier screening for spinal muscular atrophy should be offered as part of routine reproductive care. This leaves health care providers without clear guidance. In fall 2009, a meeting was held by National Institutes of Health to examine the scientific basis for spinal muscular atrophy carrier screening and to consider the issues that accompany such screening. In this article, the meeting participants summarize the discussions and conclude that pan-ethnic carrier screening for spinal muscular atrophy is technically feasible and that the specific study of implementing a spinal muscular atrophy carrier screening program raises broader issues about determining the scope and specifics of carrier screening in general. Genet Med 2010:12(10):621-622. C1 [Gitlin, Jonathan M.; Frosst, Phyllis] NHGRI, Bethesda, MD 20892 USA. [Crawford, Thomas O.] Johns Hopkins Univ, Baltimore, MD 21218 USA. [MacKenzie, Alex] Univ Ottawa, Ottawa, ON K1N 6N5, Canada. [Prior, Thomas] Ohio State Univ, Columbus, OH 43210 USA. [Lloyd-Puryear, Michele] US Hlth Resources & Serv Adm, Rockville, MD 20857 USA. [Wang, Ching] Stanford Univ, Med Ctr, Stanford, CA 94305 USA. [Yaron, Yuval] Tel Aviv Sourasky Med Ctr, Tel Aviv, Israel. [Howell, R. Rodney] Univ Miami, Miller Sch Med, Coral Gables, FL 33124 USA. RP Gitlin, JM (reprint author), NHGRI, 31 Ctr Dr,4B09, Bethesda, MD 20892 USA. EM gitlinjm@mail.nih.gov RI Gitlin, Jonathan/H-4492-2011; Crawford, Thomas/E-6307-2012 FU Intramural NIH HHS [ZIA NS003037-04] NR 5 TC 12 Z9 12 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1098-3600 J9 GENET MED JI Genet. Med. PD OCT PY 2010 VL 12 IS 10 BP 621 EP 622 DI 10.1097/GIM.0b013e3181ef6079 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA 664HH UT WOS:000282950500004 PM 20808230 ER PT J AU Sapp, JC Nishimura, D Johnston, JJ Stone, EM Heon, E Sheffield, VC Biesecker, LG AF Sapp, Julie C. Nishimura, Darryl Johnston, Jennifer J. Stone, Edwin M. Heon, Elise Sheffield, Val C. Biesecker, Leslie G. TI Recurrence risks for Bardet-Biedl syndrome: Implications of locus heterogeneity SO GENETICS IN MEDICINE LA English DT Editorial Material DE genetic heterogeneity; recurrence risks; carrier frequency; rod-cone dystrophy; obesity ID SYNDROME GENE; IDENTIFICATION; INHERITANCE; MUTATIONS; GENOMICS; PROTEIN; OBESITY; BBS2 AB Purpose: Bardet-Biedl syndrome is a pleiotropic multiple anomaly syndrome inherited in an autosomal recessive pattern. It is now known that this disorder has locus heterogeneity, with causative mutations identified in as many as 14 genes. The aim of this study was to derive locus-specific recurrence risk estimates for family members of a proband affected with Bardet-Biedl syndrome. Methods: Mutation data from 187 probands affected with Bardet-Biedl syndrome were used. The authors counted the relative proportion of families with mutations at each of 10 loci and estimated locus-specific carrier rates for mutations using Hardy-Weinberg principles and an aggregate population frequency of 1/100,000 for the phenotype. Locus-specific recurrence risks were calculated for relatives of an affected proband. Results: Locus-specific carrier frequencies range from 1/250 to 1/2200, and the risks for an offspring of the sibling of an affected individual range from 1/1,500 to 1/13,000. The estimate of this risk derived under a locus homogeneity model is 1/960. Conclusion: Variation of recurrence risks of this magnitude may have implications for genetic counseling of families with affected individuals, in particular about prenatal testing and other reproductive options. Similar analyses to determine locus-specific carrier frequencies for other phenotypes with significant locus heterogeneity may yield similarly relevant results. Genet Med 2010:12(10):623-627. C1 [Sapp, Julie C.; Johnston, Jennifer J.; Biesecker, Leslie G.] NHGRI, NIH, Bethesda, MD 20892 USA. [Nishimura, Darryl; Sheffield, Val C.] Univ Iowa Hosp & Clin, Dept Pediat, Div Med Genet, Iowa City, IA 52242 USA. [Stone, Edwin M.] Univ Iowa Hosp & Clin, Dept Ophthalmol, Iowa City, IA 52242 USA. [Heon, Elise] Hosp Sick Children, Dept Ophthalmol & Vis Sci, Toronto, ON M5G 1X8, Canada. RP Sapp, JC (reprint author), NHGRI, NIH, 10 Ctr Dr,Bldg 10,Room 3C710, Bethesda, MD 20892 USA. EM sappj@mail.nih.gov FU Howard Hughes Medical Institute; Intramural NIH HHS [ZIA HG200328-06]; NEI NIH HHS [R01-EY-11298, R01 EY011298, R01 EY017168] NR 23 TC 7 Z9 7 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1098-3600 J9 GENET MED JI Genet. Med. PD OCT PY 2010 VL 12 IS 10 BP 623 EP 627 DI 10.1097/GIM.0b013e3181f07572 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 664HH UT WOS:000282950500005 PM 20949666 ER PT J AU Estecio, MRH Gallegos, J Vallot, C Castoro, RJ Chung, W Maegawa, S Oki, Y Kondo, Y Jelinek, J Shen, LL Hartung, H Aplan, PD Czerniak, BA Liang, SD Issa, JPJ AF Estecio, Marcos R. H. Gallegos, Juan Vallot, Celine Castoro, Ryan J. Chung, Woonbok Maegawa, Shinji Oki, Yasuhiro Kondo, Yutaka Jelinek, Jaroslav Shen, Lanlan Hartung, Helge Aplan, Peter D. Czerniak, Bogdan A. Liang, Shoudan Issa, Jean-Pierre J. TI Genome architecture marked by retrotransposons modulates predisposition to DNA methylation in cancer SO GENOME RESEARCH LA English DT Article ID CPG ISLAND METHYLATION; EMBRYONIC STEM-CELLS; MYELODYSPLASTIC SYNDROME; TRANSPOSABLE ELEMENTS; GENE-EXPRESSION; MOUSE; POLYCOMB; PROMOTER; REGIONS; HYPERMETHYLATION AB Epigenetic silencing plays an important role in cancer development. An attractive hypothesis is that local DNA features may participate in differential predisposition to gene hypermethylation. We found that, compared with methylation-resistant genes, methylation-prone genes have a lower frequency of SINE and LINE retrotransposons near their transcription start site. In several large testing sets, this distribution was highly predictive of promoter methylation. Genome-wide analysis showed that 22% of human genes were predicted to be methylation-prone in cancer; these tended to be genes that are down-regulated in cancer and that function in developmental processes. Moreover, retrotransposon distribution marks a larger fraction of methylation-prone genes compared to Polycomb group protein (PcG) marking in embryonic stem cells; indeed, PcG marking and our predictive model based on retrotransposon frequency appear to be correlated but also complementary. In summary, our data indicate that retrotransposon elements, which are widespread in our genome, are strongly associated with gene promoter DNA methylation in cancer and may in fact play a role in influencing epigenetic regulation in normal and abnormal physiological states. C1 [Estecio, Marcos R. H.; Castoro, Ryan J.; Chung, Woonbok; Maegawa, Shinji; Jelinek, Jaroslav; Issa, Jean-Pierre J.] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA. [Gallegos, Juan; Liang, Shoudan] Univ Texas MD Anderson Canc Ctr, Dept Bioinformat & Computat Biol, Houston, TX 77030 USA. [Vallot, Celine] Inst Curie, CNRS, UMR 144, F-75248 Paris 05, France. [Oki, Yasuhiro] Aichi Canc Ctr Hosp & Res Inst, Dept Hematol & Cell Therapy, Nagoya, Aichi 4648681, Japan. [Kondo, Yutaka] Aichi Canc Ctr Hosp & Res Inst, Div Mol Oncol, Nagoya, Aichi 4648681, Japan. [Shen, Lanlan] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. [Hartung, Helge; Aplan, Peter D.] NCI, Genet Branch, Ctr Canc Res, NIH, Bethesda, MD 20889 USA. [Czerniak, Bogdan A.] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. RP Estecio, MRH (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA. EM mestecio@mdanderson.org; jpissa@mdanderson.org RI Jelinek, Jaroslav/D-2282-2012; Aplan, Peter/K-9064-2016; OI Jelinek, Jaroslav/0000-0002-2533-0220; Castoro, Ryan/0000-0002-3242-3775 FU Leukemia Specialized Program of Research Excellence [P50 CA100632]; National Institutes of Health [R01 CA098006, U01 CA085078] FX This work was supported by the Leukemia Specialized Program of Research Excellence grant P50 CA100632, the National Institutes of Health grants R01 CA098006 and U01 CA085078, and the NIH intramural research program. J.P.J.I. is an American Cancer Society Clinical Research Professor. We thank Stephanie P. Deming for editorial help. NR 50 TC 52 Z9 54 U1 2 U2 10 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD OCT PY 2010 VL 20 IS 10 BP 1369 EP 1382 DI 10.1101/gr.107318.110 PG 14 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 656XS UT WOS:000282375000007 PM 20716667 ER PT J AU Teer, JK Bonnycastle, LL Chines, PS Hansen, NF Aoyama, N Swift, AJ Abaan, HO Albert, TJ Margulies, EH Green, ED Collins, FS Mullikin, JC Biesecker, LG AF Teer, Jamie K. Bonnycastle, Lori L. Chines, Peter S. Hansen, Nancy F. Aoyama, Natsuyo Swift, Amy J. Abaan, Hatice Ozel Albert, Thomas J. Margulies, Elliott H. Green, Eric D. Collins, Francis S. Mullikin, James C. Biesecker, Leslie G. CA NISC Comparative Sequencing TI Systematic comparison of three genomic enrichment methods for massively parallel DNA sequencing SO GENOME RESEARCH LA English DT Article ID MULTIPLEX AMPLIFICATION; HYBRID SELECTION; EXON CAPTURE; HYBRIDIZATION AB Massively parallel DNA sequencing technologies have greatly increased our ability to generate large amounts of sequencing data at a rapid pace. Several methods have been developed to enrich for genomic regions of interest for targeted sequencing. We have compared three of these methods: Molecular Inversion Probes (MIP), Solution Hybrid Selection (SHS), and Microarray-based Genomic Selection (MGS). Using HapMap DNA samples, we compared each of these methods with respect to their ability to capture an identical set of exons and evolutionarily conserved regions associated with 528 genes (2.61 Mb). For sequence analysis, we developed and used a novel Bayesian genotype-assigning algorithm, Most Probable Genotype (MPG). All three capture methods were effective, but sensitivities (percentage of targeted bases associated with high-quality genotypes) varied for an equivalent amount of pass-filtered sequence: for example, 70% (MIP), 84% (SHS), and 91% (MGS) for 400 Mb. In contrast, all methods yielded similar accuracies of >99.84% when compared to Infinium 1M SNP BeadChip-derived genotypes and >99.998% when compared to 30-fold coverage whole-genome shotgun sequencing data. We also observed a low false-positive rate with all three methods; of the heterozygous positions identified by each of the capture methods, >99.57% agreed with 1M SNP BeadChip, and >98.840% agreed with the whole-genome shotgun data. In addition, we successfully piloted the genomic enrichment of a set of 12 pooled samples via the MGS method using molecular bar codes. We find that these three genomic enrichment methods are highly accurate and practical, with sensitivities comparable to that of 30-fold coverage whole-genome shotgun data. C1 [Teer, Jamie K.; Bonnycastle, Lori L.; Chines, Peter S.; Hansen, Nancy F.; Swift, Amy J.; Abaan, Hatice Ozel; Margulies, Elliott H.; Green, Eric D.; Collins, Francis S.; Mullikin, James C.; Biesecker, Leslie G.; NISC Comparative Sequencing] NHGRI, NIH, Bethesda, MD 20892 USA. [Aoyama, Natsuyo; Albert, Thomas J.] Roche NimbleGen Inc, Madison, WI 53719 USA. RP Collins, FS (reprint author), NHGRI, NIH, Bethesda, MD 20892 USA. EM collinsf@mail.nih.gov; mullikin@mail.nih.gov; leslieb@helix.nih.gov FU National Human Genome Research Institute FX This study was supported by the Intramural Research Program of the National Human Genome Research Institute. We express our gratitude to Darryl Leja for his assistance with figure preparation. We thank Agilent Technologies for providing SureSelect probes and Illumina Inc. for genotyping data from the Infinium Human 1Mv1.0 BeadChip. We also thank Emily Turner and Jay Shendure at the University of Washington and Sheila Fisher and Chad Nussbaum at the Broad Institute for ongoing discussions relating to MIP and SHS, respectively. We also thank several individuals for their help with MGS: Kari Kubalanza for technical assistance with the pilot study, Narisu Narisu for help with interim analyses, and Mike Erdos for ongoing discussions. NR 25 TC 117 Z9 118 U1 0 U2 16 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD OCT PY 2010 VL 20 IS 10 BP 1420 EP 1431 DI 10.1101/gr.106716.110 PG 12 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 656XS UT WOS:000282375000012 PM 20810667 ER PT J AU Stenholm, S Simonsick, EM Ferrucci, L AF Stenholm, S. Simonsick, E. M. Ferrucci, L. TI SECULAR TRENDS IN BODY WEIGHT: EVIDENCE OF AN EPIDEMIC OF INCREASING FATNESS FROM THE BLSA SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Simonsick, E. M.; Ferrucci, L.] NIA, Baltimore, MD 21224 USA. [Stenholm, S.] Natl Inst Hlth & Welf, Turku, Finland. RI Stenholm, Sari/G-6940-2011 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 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 124 EP 125 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006701597 ER PT J AU Ferrucci, L Schrack, J Stenholm, S Metter, EJ Simonsick, EM AF Ferrucci, L. Schrack, J. Stenholm, S. Metter, E. J. Simonsick, E. M. TI ANTHROPOMETRIC PREDICTORS OF RESTING METABOLIC RATE (RMR) IN HEALTHY OLDER PERSONS SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Ferrucci, L.; Schrack, J.; Metter, E. J.; Simonsick, E. M.] NIA, Baltimore, MD 21224 USA. [Schrack, J.; Simonsick, E. M.] Johns Hopkins Med Inst, Baltimore, MD 21205 USA. [Stenholm, S.] Natl Inst Hlth & Welf, Turku, Finland. RI Stenholm, Sari/G-6940-2011 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 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 125 EP 125 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006701598 ER PT J AU Koster, A Kim, LJ Eiriksdottir, G Gudnason, V Aspelund, T Launer, LJ Harris, T AF Koster, A. Kim, L. J. Eiriksdottir, G. Gudnason, V. Aspelund, T. Launer, L. J. Harris, T. TI FAT DISTRIBUTION AND MORTALITY: THE AGES-REYKJAVIK STUDY SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Koster, A.; Kim, L. J.; Launer, L. J.; Harris, T.] NIA, Bethesda, MD 20892 USA. [Eiriksdottir, G.; Gudnason, V.; Aspelund, T.] Iceland Heart Assoc, Reykjavik, Iceland. RI Aspelund, Thor/F-4826-2011; Aspelund, Thor/C-5983-2008; Gudnason, Vilmundur/K-6885-2015 OI Aspelund, Thor/0000-0002-7998-5433; Gudnason, Vilmundur/0000-0001-5696-0084 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 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 246 EP 246 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006702300 ER PT J AU Casanova, R Espeland, MA Goveas, J Davatzikos, C Gaussoin, SA Wagner, B Maldjian, JA Resnick, SM AF Casanova, R. Espeland, M. A. Goveas, J. Davatzikos, C. Gaussoin, S. A. Wagner, B. Maldjian, J. A. Resnick, S. M. TI APPLICATION OF MACHINE LEARNING METHODS TO DESCRIBE THE EFFECTS OF CONJUGATED EQUINE ESTROGENS THERAPY ON REGION-SPECIFIC BRAIN VOLUMES SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Casanova, R.; Espeland, M. A.; Gaussoin, S. A.] Wake Forest Univ Hlth Sci, Dept Biostat Sci, Winston Salem, NC USA. [Goveas, J.] Med Coll Wisconsin, Dept Psychiat, Milwaukee, WI 53226 USA. [Davatzikos, C.] Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA. [Wagner, B.; Maldjian, J. A.] Wake Forest Univ Hlth Sci, Dept Radiol, Winston Salem, NC USA. [Resnick, S. M.] NIA, Baltimore, MD 21224 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 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 308 EP 309 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006702598 ER PT J AU Tanaka, T Semba, R Walston, JD Singleton, A Hernandez, D Bandinelli, S Ferrucci, L AF Tanaka, T. Semba, R. Walston, J. D. Singleton, A. Hernandez, D. Bandinelli, S. Ferrucci, L. TI GENETICS OF OXIDATIVE STRESS: AGER GENE VARIANTS AND ADVANCED GLYCATION END PRODUCT RECEPTOR SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Tanaka, T.; Singleton, A.; Hernandez, D.; Ferrucci, L.] NIA, Baltimore, MD USA. [Semba, R.; Walston, J. D.] Johns Hopkins Univ, Baltimore, MD USA. [Bandinelli, S.] Azienda Sanitaria Firenze, Florence, Italy. RI Singleton, Andrew/C-3010-2009 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 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 340 EP 340 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006702741 ER PT J AU Tolea, M Costa, PT Terracciano, A Ferrucci, L Faulkner, K Coday, M Ayonayon, HN Simonsick, E AF Tolea, M. Costa, P. T. Terracciano, A. Ferrucci, L. Faulkner, K. Coday, M. Ayonayon, H. N. Simonsick, E. TI PERSONALITY AND WALKING SPEED DECLINE: FINDINGS FROM THE HEALTH, AGING AND BODY COMPOSITION STUDY SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Tolea, M.; Costa, P. T.; Terracciano, A.; Ferrucci, L.; Simonsick, E.] NIA, Baltimore, MD 21224 USA. [Faulkner, K.] NIOSH, Natl Personal Protect Technol Lab OD, Atlanta, GA USA. [Coday, M.] Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA. [Ayonayon, H. N.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RI terracciano, antonio/B-1884-2008 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 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 340 EP 340 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006702742 ER PT J AU Flaherty, JH Dong, B Wu, H Zhang, Y Malmstrom, T Guralnik, J Morley, JE AF Flaherty, J. H. Dong, B. Wu, H. Zhang, Y. Malmstrom, T. Guralnik, J. Morley, J. E. TI STRESS-RELATED MORTALITY AFTER A MAJOR EARTHQUAKE AMONG CHINESE NONAGENARIANS SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Malmstrom, T.] St Louis Univ, Dept Neurol & Psychiat, St Louis, MO 63103 USA. [Flaherty, J. H.] St Louis VA GRECC, St Louis, MO USA. [Dong, B.; Wu, H.; Zhang, Y.] Sichuan Univ, W China Hosp, Chengdu 610064, Sichuan, Peoples R China. [Guralnik, J.] NIA, NIH, Baltimore, MD 21224 USA. RI morley, john/F-9177-2011 OI morley, john/0000-0001-6444-2965 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 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 370 EP 371 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006703014 ER PT J AU Chang, M Saczynski, J Aspelund, T Gudnason, V Harris, TB Launer, LJ Jonsson, PV AF Chang, M. Saczynski, J. Aspelund, T. Gudnason, V. Harris, T. B. Launer, L. J. Jonsson, P. V. TI THE ASSOCIATION BETWEEN MIDLIFE BODY MASS INDEX AND COGNITIVE FUNCTION IN LATE LIFE: AGE GENE/ENVIRONMENT SUSCEPTIBILITY - REYKJAVIK STUDY SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Chang, M.; Jonsson, P. V.] Landspitali Univ Hosp, Reykjavik, Iceland. [Saczynski, J.] Univ Massachusetts, Worcester, MA 01605 USA. [Aspelund, T.; Gudnason, V.; Jonsson, P. V.] Univ Iceland, Reykjavik, Iceland. [Aspelund, T.; Gudnason, V.] Iceland Heart Assoc, Kopavogur, Iceland. [Harris, T. B.; Launer, L. J.] NIA, Bethesda, MD 20892 USA. RI Aspelund, Thor/F-4826-2011; Aspelund, Thor/C-5983-2008; Gudnason, Vilmundur/K-6885-2015 OI Aspelund, Thor/0000-0002-7998-5433; Gudnason, Vilmundur/0000-0001-5696-0084 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 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 441 EP 441 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006703353 ER PT J AU Fontana, RJ Dienstag, JL Bonkovsky, HL Sterling, RK Naishadham, D Goodman, ZD Lok, ASF Wright, EC Su, GL AF Fontana, Robert J. Dienstag, Jules L. Bonkovsky, Herbert L. Sterling, Richard K. Naishadham, Deepa Goodman, Zachary D. Lok, Anna S. F. Wright, Elizabeth C. Su, Grace L. CA HALT-C Trial Grp TI Serum fibrosis markers are associated with liver disease progression in non-responder patients with chronic hepatitis C SO GUT LA English DT Article ID COMPENSATED CIRRHOSIS; INTERFERON THERAPY; RANDOMIZED-TRIAL; HYALURONIC-ACID; YKL-40; STEATOSIS; RIBAVIRIN; VIRUS; PEGINTERFERON; VARIABILITY AB Objectives The aim of this study was to explore the association of serum fibrosis marker levels with the risk of clinical and histological disease progression in a large cohort of patients with chronic hepatitis C (CHC). Methods 462 prior non-responders to peginterferon and ribavirin enrolled in the randomised phase of the Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) Trial had baseline and annual serum samples tested for hyaluronic acid (HA), N-terminal peptide of procollagen type 3, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) and YKL-40. All patients underwent a pretreatment liver biopsy and follow-up biopsies at years 2 and 4. Histological progression was defined as a >= 2 point increase in Ishak fibrosis score in patients without cirrhosis. Clinical outcomes included development of decompensation, hepatocellular cancer, death or an increase in the CTP (Child-Turcotte-Pugh) score to >= 7. Results Mean patient age was 49.5 years and 39% had histological cirrhosis at entry. Baseline HA, YKL-40 and TIMP-1 levels combined with other laboratory parameters were all significantly associated with clinical outcomes in the 69 (15%) patients with disease progression (p<0.0001). The best multivariate model to predict clinical outcomes included baseline bilirubin, albumin, international normalised ratio (INR) and YKL-40 levels. All of the baseline serum fibrosis marker levels were also significantly associated with histological fibrosis progression that developed in 70 (33%) of the 209 patients with cirrhosis (p<0.0001). However, baseline HA and platelet counts were best at predicting histological progression (area under the curve (AUC)=0.663). Conclusion Pretreatment serum fibrosis marker levels are significantly increased in patients with CHC at risk of clinical and histological disease progression. If validated in additional cohorts, measurement of these markers could help identify patients with CHC who would benefit from more frequent and intensive monitoring. C1 [Fontana, Robert J.] Univ Michigan, Dept Internal Med, Taubman Ctr 3912, Sch Med, Ann Arbor, MI 48109 USA. [Dienstag, Jules L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit,Med Serv, Boston, MA USA. [Dienstag, Jules L.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Bonkovsky, Herbert L.] Univ Connecticut, Ctr Hlth, Dept Med, Storrs, CT 06269 USA. [Bonkovsky, Herbert L.] Univ Connecticut, Ctr Hlth, Dept Mol & Struct Biol, Storrs, CT 06269 USA. [Bonkovsky, Herbert L.] Univ Connecticut, Ctr Hlth, Liver Biliary Pancreat Ctr, Storrs, CT 06269 USA. [Sterling, Richard K.] Virginia Commonwealth Univ Med Ctr, Hepatol Sect, Richmond, VA USA. [Naishadham, Deepa] Tufts Univ New England Med Ctr, Boston, MA USA. [Wright, Elizabeth C.] NIDDKD, NIH, Dept Hlth & Human Serv, Baltimore, MD USA. RP Fontana, RJ (reprint author), Univ Michigan, Dept Internal Med, Taubman Ctr 3912, Sch Med, Ann Arbor, MI 48109 USA. EM rfontana@med.umich.edu OI Yang, Shuman/0000-0002-9638-0890 FU National Institute of Diabetes & Digestive & Kidney Diseases; National Center for Research Resources, National Institutes of Health; Hoffmann-La Roche; National Institutes of Health; University of Massachusetts Medical Center, Worcester, Massachusetts [N01-DK-9-2326]; University of Connecticut Health Center, Farmington, Connecticut [M01RR-06192]; Massachusetts General Hospital, Boston, Massachusetts (Harvard Clinical and Translational Science Center) [N01-DK-9-2319, M01RR-01066, 1 UL1 RR025758-01]; University of Michigan Medical Center, Ann Arbor, Michigan (Michigan Center for Clinical and Health Research) [N01-DK-9-2323, M01RR-00042, 1 UL1 RR024986]; Virginia Commonwealth University Health System, Richmond, Virginia [N01-DK-9-2322, M01RR-00065]; National Institute of Diabetes and Digestive and Kidney Diseases, Division of Digestive Diseases and Nutrition, Bethesda, Maryland; New England Research Institutes, Watertown, Massachusetts [N01-DK-9-2328]; Armed Forces Institute of Pathology, Washington, DC FX This study was supported by the National Institute of Diabetes & Digestive & Kidney Diseases (contract numbers are listed below). Additional support was provided by the National Institute of Allergy and Infectious Diseases (NIAID), the National Cancer Institute, the National Center for Minority Health and Health Disparities and by General Clinical Research Center and Clinical and Translational Science Center grants from the National Center for Research Resources, National Institutes of Health (grant numbers are listed below). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center for Research Resources or the National Institutes of Health. Additional funding to conduct this study was supplied by Hoffmann-La Roche, through a Cooperative Research and Development Agreement (CRADA) with the National Institutes of Health. In addition to the authors of this manuscript, the following individuals were instrumental in the planning, conduct and/or care of patients enrolled in this study at each of the participating institutions as follows: University of Massachusetts Medical Center, Worcester, Massachusetts (contract N01-DK-9-2326), Gyongyi Szabo, Barbara F Banner, Maureen Cormier, Donna Giansiracusa; University of Connecticut Health Center, Farmington, Connecticut (grant M01RR-06192), Gloria Borders, Michelle Kelley; Massachusetts General Hospital, Boston, Massachusetts (contract N01-DK-9-2319, grant M01RR-01066; grant 1 UL1 RR025758-01, Harvard Clinical and Translational Science Center), Raymond T Chung, Andrea E Reid, Atul K Bhan, Wallis A Molchen, Cara C Gooch; University of Michigan Medical Center, Ann Arbor, Michigan (contract N01-DK-9-2323, grant M01RR-00042, grant 1 UL1 RR024986, Michigan Center for Clinical and Health Research), Joel K Greenson, Pamela A Richtmyer, R Tess Bonham; Virginia Commonwealth University Health System, Richmond, Virginia (contract N01-DK-9-2322, grant M01RR-00065), Mitchell L Shiffman, Melissa J Contos, A Scott Mills, Charlotte Hofmann, Paula Smith; National Institute of Diabetes and Digestive and Kidney Diseases, Division of Digestive Diseases and Nutrition, Bethesda, Maryland, James E. Everhart, Leonard B Seeff, Patricia R Robuck, Jay H Hoofnagle; New England Research Institutes, Watertown, Massachusetts (contract N01-DK-9-2328), Kristin K Snow, Margaret C Bell, Teresa M Curto; Armed Forces Institute of Pathology, Washington, DC, Fanny Monge, Michelle Parks; Data and Safety Monitoring Board Members: (Chair) Gary L. Davis, Guadalupe Garcia-Tsao, Michael Kutner, Stanley M. Lemon, Robert P. Perrillo. NR 44 TC 52 Z9 53 U1 1 U2 2 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 OCT PY 2010 VL 59 IS 10 BP 1401 EP 1409 DI 10.1136/gut.2010.207423 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 660RN UT WOS:000282661300020 PM 20675691 ER PT J AU Ghosh, S Albitar, L LeBaron, R Welch, WR Samimi, G Birrer, MJ Berkowitz, RS Mok, SC AF Ghosh, Sue Albitar, Lina LeBaron, Richard Welch, William R. Samimi, Goli Birrer, Michael J. Berkowitz, Ross S. Mok, Samuel C. TI Up-regulation of stromal versican expression in advanced stage serous ovarian cancer SO GYNECOLOGIC ONCOLOGY LA English DT Article DE Versican; Stroma; Ovarian cancer ID EXTRACELLULAR-MATRIX; DIFFERENTIAL EXPRESSION; CELL INVASION; TUMORS; HYALURONAN; ISOFORMS AB Objective. The purpose of this study is to examine the role of versican (VCAN) in advanced stage serous ovarian cancer by investigating its expression, its function, and its correlation with clinical outcomes. Methods. Microarray analysis was performed on RNA isolated from tumor and stromal components of advanced stage serous ovarian cancer and normal ovarian epithelial tissue to identify genes up-regulated in ovarian tumor stroma. Validation studies using immunohistochemistry and quantitative real-time PCR (Q-RTPCR) was performed on one of the up-regulated genes, VCAN. Immunolocalization of VCAN (n = 111) and CD31 (n = 56) was done on serous ovarian tumors. CD31 staining was performed to examine microvessel density (MVD). Q-RT-PCR was performed on 65 samples to evaluate the differential expression of VCAN isoforms. Cell proliferation and invasion assays were performed to examine how V1-treated ovarian cancer cell lines and an endothelial cell line would differ from controls. Univariate survival analyses were done with VCAN expression. Correlation analysis was done with CD31, platinum resistance, and clinical data. Results. Validation studies using Q-RT-PCR and immunohistochemistry showed significantly higher VCAN V1 isoform expression in ovarian cancer stroma compared with normal ovarian stroma and ovarian cancer cells. Correlation studies showed stromal VCAN expression was associated with poorer overall and progression-free survival, platinum resistance, and increased MVD. VCAN-treated ovarian cancer and endothelial cells showed increased invasion potential. Conclusions. VCAN overexpression is associated with increased MVD and invasion potential, which may lead to poorer overall and progression-free survival and platinum resistance. (C) 2010 Elsevier Inc. All rights reserved. C1 [Mok, Samuel C.] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol, Houston, TX 77030 USA. [Ghosh, Sue; Berkowitz, Ross S.] Brigham & Womens Hosp, Div Gynecol Oncol, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. [Albitar, Lina] Brigham & Womens Hosp, Dept Med, Genet Lab, Boston, MA 02115 USA. [LeBaron, Richard] Univ Texas San Antonio, Dept Biol, San Antonio, TX USA. [Welch, William R.] Brigham & Womens Hosp, Dept Pathol, Div Womens & Perinatal Pathol, Boston, MA 02115 USA. [Samimi, Goli] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Birrer, Michael J.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Mok, SC (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol, T4-3908,1515 Holcombe Blvd, Houston, TX 77030 USA. EM scmok@mdanderson.org RI LeBaron, Richard/K-4722-2013 OI LeBaron, Richard/0000-0002-7770-305X FU Dana-Farber/Harvard Cancer Center [P50CA165009]; National Institute of Health [P50CA083639, RO1CA133057, R33CA103595]; Department of Health and Human Services; Gillette Center For Women's Cancer; Adler Foundation, Inc.; Edgar Astrove Fund; Ovarian Cancer Research Fund, Inc.; Morse Family Fund; Natalie Pihl Fund; Ruth N. White Research Fellowship; Friends of Dana-Farber Cancer Institute; Robert and Deborah First Fund; National Cancer Institute FX This study was supported in part by the Dana-Farber/Harvard Cancer Center Ovarian Cancer SPORE grant P50CA165009, the M.D. Anderson Ovarian Cancer SPORE grant P50CA083639, RO1CA133057 and R33CA103595 from National Institute of Health, Department of Health and Human Services, Gillette Center For Women's Cancer, Adler Foundation, Inc., Edgar Astrove Fund, the Ovarian Cancer Research Fund, Inc., the Morse Family Fund, the Natalie Pihl Fund, the Ruth N. White Research Fellowship, Friends of Dana-Farber Cancer Institute, the Robert and Deborah First Fund, and the intramural research program of the National Cancer Institute. NR 26 TC 24 Z9 26 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 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD OCT PY 2010 VL 119 IS 1 BP 114 EP 120 DI 10.1016/j.ygyno.2010.05.029 PG 7 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 657AN UT WOS:000282382500020 PM 20619446 ER PT J AU Rasmussen, T Haaber, J Dah, IM Knudsen, LM Kerndrup, GB Lodahl, M Johnsen, HE Kuehl, M AF Rasmussen, Thomas Haaber, Jacob Dah, Inger Marie Knudsen, Lene M. Kerndrup, Gitte B. Lodahl, Marianne Johnsen, Hans E. Kuehl, Michael TI Identification of translocation products but not K-RAS mutations in memory B cells from patients with multiple myeloma SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Article DE multiple myeloma; monoclonal gammopathy of undetermined significance; memory B cells; K-RAS; clonotype ID POLYMERASE-CHAIN-REACTION; MALIGNANT PLASMA-CELL; BONE-MARROW; MONOCLONAL GAMMOPATHY; UNDETERMINED SIGNIFICANCE; QUANTITATIVE-ANALYSIS; ACTIVATING MUTATIONS; PERIPHERAL-BLOOD; MESSENGER-RNA; CD19(+) CELLS AB Background Several laboratories have shown that cells with a memory B-cell phenotype can have the same clonotype as multiple myeloma tumor cells. Design and Methods The aim of this study was to determine whether some memory B cells have the same genetic alterations as their corresponding multiple myeloma malignant plasma cells. The methodology included sorting multiple myeloma or memory B cells into RNA stabilizing medium for generation of subset-specific polymerase chain reaction complementary DNA libraries from one or 100 cells. Results Cells with the phenotype of tumor plasma cells (CD38(++)CD19(-)CD45(-/+)CD56(-/+/++)) or memory B cells (CD38(-)/CD19(+)/CD27(+)) were isolated by flow activated cell sorting. In samples from all four patients with multiple myeloma and from two of the three with monoclonal gammopathy of undetermined significance, we identified memory B cells expressing multiple myeloma-specific oncogenes (FGER3; IGH-MMSET; CCND1 high) dysregulated by an IGH translocation in the respective tumor plasma cells. By contrast, in seven patients with multiple myeloma, each of whom had tumor plasma cells with a K-RAS61 mutation, a total of 32,400 memory B cells were analyzed using a sensitive allele-specific, competitive blocker polymerase chain reaction assay, but no K-RAS mutations were identified. Conclusions The increased expression of a specific "early" oncogene of multiple myeloma (monoclonal gammopathy of undetermined significance) in some memory B cells suggests that dysregulation of the oncogene occurs in a precursor B-cell that can generate memory B cells and transformed plasma cells. However, if memory B cells lack "late" oncogene (K-RAS) mutations but express the "early" oncogene, they cannot be involved in maintaining the multiple myeloma tumor, but presumably represent a clonotypic remnant that is only partially transformed. C1 [Kuehl, Michael] NCI, Genet Branch, Ctr Canc Res, NIH,Bethesda Naval Hosp, Bethesda, MD 20889 USA. [Rasmussen, Thomas; Knudsen, Lene M.; Lodahl, Marianne; Johnsen, Hans E.] Univ Copenhagen, Herlev Hosp, Dept Hematol, DK-2730 Herlev, Denmark. [Haaber, Jacob; Knudsen, Lene M.; Kerndrup, Gitte B.] Odense Univ Hosp, Dept Hematol, DK-5000 Odense, Denmark. [Dah, Inger Marie] Univ Hosp, Sect Hematol, Tromso, Norway. [Johnsen, Hans E.] Aarhus Univ Hosp, Aalborg Hosp, Dept Hematol, Aarhus, Denmark. RP Kuehl, M (reprint author), NCI, Genet Branch, Ctr Canc Res, NIH,Bethesda Naval Hosp, Bldg 8,Room 5101, Bethesda, MD 20889 USA. EM wmk@helix.nih.gov FU Danish Cancer Society [DP 00006, DP 22-00-0314, DP 2002-04]; Multiple Myeloma Research Foundation [2003-4]; EU [LSHC-CT-2006-037602]; NIH, National Cancer Institute, Center for Cancer Research FX this project was supported in part by the Danish Cancer Society, grant number DP 00006 to TR and DP 22-00-0314 and DP 2002-04 to HEJ. HE) was supported by a senior grant from the Multiple Myeloma Research Foundation 2003-4 and EU 6th FP to MSC-NET (LSHC-CT-2006-037602) and MK was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 47 TC 27 Z9 28 U1 0 U2 4 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD OCT PY 2010 VL 95 IS 10 BP 1730 EP 1737 DI 10.3324/haematol.2010.024778 PG 8 WC Hematology SC Hematology GA 668MV UT WOS:000283275000017 PM 20511669 ER PT J AU Simpson, LA Peterson, L Lannon, CM Murphy, SB Goodman, C Ren, ZX Zajicek, A AF Simpson, Lisa A. Peterson, Laura Lannon, Carole M. Murphy, Sharon B. Goodman, Clifford Ren, Zhaoxia Zajicek, Anne TI Special Challenges In Comparative Effectiveness Research On Children's And Adolescents' Health SO HEALTH AFFAIRS LA English DT Article ID SERVICES RESEARCH; CLINICAL-TRIALS; STRATEGIES; CARE; POLICY AB The United States is undertaking a major expansion of comparative effectiveness research, with the potential to achieve systemwide improvements in health care quality, outcomes, and resource allocation. However, to achieve these improvements in children's health and health care, comparative effectiveness research needs to be targeted, designed, conducted, and reported in ways that are responsive to the unique circumstances of children and adolescents. These include clinically important differences in the type and course of disease in children; demographic differences between the overall child and adult population in the United States, such as racial and ethnic makeup; and methodological issues involving study design. Our overarching point is that the base of evidence in pediatrics must not fall even further behind that for the adult population in an era of rapid advancement and funding of comparative effectiveness research. C1 [Simpson, Lisa A.; Lannon, Carole M.] Cincinnati Childrens Hosp, Child Policy Res Ctr, Med Ctr, Cincinnati, OH USA. [Peterson, Laura] Univ Penn, Wharton Sch, Philadelphia, PA 19104 USA. [Lannon, Carole M.] Univ Cincinnati, Cincinnati, OH 45221 USA. [Murphy, Sharon B.] Natl Acad Sci, Inst Med, Washington, DC 20418 USA. [Ren, Zhaoxia] Eunice Kennedy Shriver Child Hlth & Human Dev NIC, Obstet & Pediat Pharmacol Branch, Natl Inst Hlth, Bethesda, MD USA. [Zajicek, Anne] NICHD, Obstet & Pediat Pharmacol Branch, Bethesda, MD USA. RP Simpson, LA (reprint author), Cincinnati Childrens Hosp, Child Policy Res Ctr, Med Ctr, Cincinnati, OH USA. EM lisa.simpson@cchmc.org FU Eunice Kennedy Shriver National Institute of Child Health and Human Development FX This study was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, to support the Obstetric and Pediatric Pharmacology Branch in its work related to the Best Pharmaceuticals for Children Act. The views expressed in this article represent the opinions of the authors and not necessarily those of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The two authors from Cincinnati Children's Hospital Medical Center are affiliated with the pediatric Center for Education and Research on Therapeutics. The authors acknowledge Adam Carle and Eric Caplan for comments and input on a draft of a report that served as a source for this article. NR 33 TC 14 Z9 14 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 OCT PY 2010 VL 29 IS 10 BP 1849 EP 1856 DI 10.1377/hlthaff.2010.0594 PG 8 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 658TZ UT WOS:000282513600015 PM 20921485 ER PT J AU Weiss, ES Taber, SK Breslau, ES Lillie, SE Li, YL AF Weiss, Elisa S. Taber, Shahnaz K. Breslau, Erica S. Lillie, Sarah E. Li, Yuelin TI The Role of Leadership and Management in Six Southern Public Health Partnerships: A Study of Member Involvement and Satisfaction SO HEALTH EDUCATION & BEHAVIOR LA English DT Article DE public health partnerships; partnership leadership; partnership research; partnership evaluation ID COMMUNITY-BASED COALITIONS; GOVERNANCE PROCESSES; UNITED-STATES; PROMOTION; PARTICIPATION; PREVENTION; CAPACITY; COLLABORATION; FRAMEWORK; SYNERGY AB Research has led to greater understanding of what is needed to create and sustain well-functioning public health partnerships. However, a partnership's ability to foster an environment that encourages broad member involvement in discussions, decision making, and activities has received scant empirical attention. This study examined the relationship between partnership members' perceptions of how well leadership and management facilitated their involvement, and their satisfaction with their role and influence within the partnership. Data came from 60 individuals who participated in two waves of a quantitative process evaluation of six southern interorganizational partnerships, formed as part of a national pilot project to increase cervical and breast cancer screening rates. Results suggested that environments fostering broad partner involvement were associated with measures of member satisfaction, controlling for other partnership characteristics. Findings indicated that facilitation of member involvement deserves increased consideration from researchers and practitioners as an indicator of the quality of partnership functioning. C1 [Weiss, Elisa S.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. [Taber, Shahnaz K.; Breslau, Erica S.; Lillie, Sarah E.] NCI, Bethesda, MD 20892 USA. [Li, Yuelin] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Weiss, ES (reprint author), Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, 3300 Kossuth Ave, Bronx, NY 10467 USA. EM elisa.weiss@einstein.yu.edu OI Lillie, Sarah/0000-0001-9854-7191 NR 78 TC 10 Z9 10 U1 2 U2 9 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1090-1981 J9 HEALTH EDUC BEHAV JI Health Educ. Behav. PD OCT PY 2010 VL 37 IS 5 BP 737 EP 752 DI 10.1177/1090198110364613 PG 16 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 660KK UT WOS:000282641000008 PM 20930135 ER PT J AU Gerstenblith, MR Goldstein, AM Tucker, MA AF Gerstenblith, Meg R. Goldstein, Alisa M. Tucker, Margaret A. TI Hereditary Genodermatoses with Cancer Predisposition SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article DE Genodermatoses; Nevoid basal cell carcinoma syndrome; Neurofibromatosis type 1; Neurofibromatosis type 2; Tuberous sclerosis; Melanoma; Xeroderma pigmentosum; Dyskeratosis congenita ID TUBEROUS SCLEROSIS COMPLEX; BASAL-CELL CARCINOMA; BILATERAL ACOUSTIC NEUROFIBROMATOSIS; GENOTYPE-PHENOTYPE CORRELATIONS; MELANOMA-PRONE FAMILIES; POPULATION-BASED PREVALENCE; POLYCYSTIC KIDNEY-DISEASE; GENOME-WIDE ASSOCIATION; GERM-LINE MUTATIONS; CDKN2A MUTATIONS AB In this article hereditary genodermatoses with cancer predisposition are reviewed, including nevoid basal cell carcinoma syndrome, neurofibromatosis types 1 and 2, tuberous sclerosis complex, xeroderma pigmentosum, and dyskeratosis congenita. Hereditary melanoma is also included, though it differs from the others in several respects. The underlying genetic aberrations causing these syndromes are largely known, allowing novel treatments to be developed for some of these disorders. Early recognition and diagnosis allows for close follow-up and surveillance for associated malignancies. C1 [Gerstenblith, Meg R.; Goldstein, Alisa M.; Tucker, Margaret A.] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RP Gerstenblith, MR (reprint author), NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bldg EPS,Room 7003,6120 Execut Blvd, Bethesda, MD 20892 USA. EM gerstenblithm@gmail.com RI Tucker, Margaret/B-4297-2015 FU NIH, National Cancer Institute, Division of Cancer Epidemiology and Genetics FX This study was supported by the Intramural Research Program of NIH, National Cancer Institute, Division of Cancer Epidemiology and Genetics. NR 196 TC 9 Z9 9 U1 0 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8588 EI 1558-1977 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD OCT PY 2010 VL 24 IS 5 BP 885 EP + DI 10.1016/j.hoc.2010.06.003 PG 23 WC Oncology; Hematology SC Oncology; Hematology GA 654GK UT WOS:000282156300007 PM 20816579 ER PT J AU Sterling, RK Wright, EC Morgan, TR Seeff, LB Hoefs, JC Di Bisceglie, AM Dienstag, JL Lok, AS AF Sterling, Richard K. Wright, Elizabeth C. Morgan, Timothy R. Seeff, Leonard B. Hoefs, John C. Di Bisceglie, Adrian M. Dienstag, Jules L. Lok, Anna S. TI FREQUENCY OF ELEVATED HEPATOCELLULAR CARCINOMA (HCC) BIOMARKERS (AFP, AFP-L3, AND DCP) IN PATIENTS WITH CHRONIC HEPATITIS C (CHC)AND ADVANCED FIBROSIS WITH AND WITHOUT HCC SO HEPATOLOGY LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 29-NOV 02, 2010 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Sterling, Richard K.] Virginia Commonwealth Univ, Div Gastroenterol & Hepatol, Richmond, VA USA. [Wright, Elizabeth C.; Seeff, Leonard B.] NIDDK, NIH, Bethesda, MD USA. [Morgan, Timothy R.] VA Long Beach Healthcare Syst, Long Beach, CA USA. [Hoefs, John C.] Univ Calif Irvine, Ann Arbor, MI USA. [Di Bisceglie, Adrian M.] St Louis Univ, St Louis, MO 63103 USA. [Dienstag, Jules L.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. [Lok, Anna S.] Univ Michagan, Ann Arbor, MI USA. NR 0 TC 3 Z9 3 U1 1 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2010 VL 52 IS 4 SU S MA 18 BP 328A EP 328A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 740EY UT WOS:000288775600019 ER PT J AU Lavine, JE Schwimmer, JB Molleston, JP Chalasani, NP Rosenthal, P Murray, KF Abrams, SH Scheimann, AO Sanyal, AJ Brunt, EM Kleiner, DE Robuck, PR Van Natta, M Unalp, A Tonascia, J AF Lavine, Joel E. Schwimmer, Jeffrey B. Molleston, Jean P. Chalasani, Naga P. Rosenthal, Philip Murray, Karen F. Abrams, Stephanie H. Scheimann, Ann O. Sanyal, Arun J. Brunt, Elizabeth M. Kleiner, David E. Robuck, Patricia R. Van Natta, Mark Unalp, Aynur Tonascia, James TI VITAMIN E, METFORMIN OR PLACEBO FOR TREATMENT OF NONALCOHOLIC FATTY LIVER DISEASE IN CHILDREN SO HEPATOLOGY LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 29-NOV 02, 2010 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Lavine, Joel E.] Columbia Univ, New York, NY USA. [Schwimmer, Jeffrey B.] Univ Calif San Diego, San Diego, CA 92103 USA. [Molleston, Jean P.; Chalasani, Naga P.] Indiana Univ, Indianapolis, IN 46204 USA. [Rosenthal, Philip] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Murray, Karen F.] Univ Washington, Seattle, WA 98195 USA. [Abrams, Stephanie H.] Baylor Univ, Houston, TX 77030 USA. [Sanyal, Arun J.] Virginia Commonwealth Univ, Richmond, VA USA. [Brunt, Elizabeth M.] Washington Univ, St Louis, MO USA. [Kleiner, David E.] NIH, Bethesda, MD 20892 USA. [Robuck, Patricia R.] NIDDK, Bethesda, MD USA. [Van Natta, Mark; Unalp, Aynur; Tonascia, James] Johns Hopkins, Data Coordinating Ctr, Baltimore, MD USA. [Scheimann, Ann O.] Johns Hopkins, Pediat, Baltimore, MD USA. NR 0 TC 3 Z9 3 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2010 VL 52 IS 4 SU S MA 110 BP 374A EP 375A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 740EY UT WOS:000288775600111 ER PT J AU O'Brien, TR Everhart, JE Chung, RT Morgan, TR Bonkovsky, HL Shao, YW Lok, AS Shiffman, ML Sninsky, J Pfeiffer, R AF O'Brien, Thomas R. Everhart, James E. Chung, Raymond T. Morgan, Timothy R. Bonkovsky, Herbert L. Shao, Yongwu Lok, Anna S. Shiffman, Mitchell L. Sninsky, John Pfeiffer, Ruth TI AN IL28B GENOTYPE-BASED MODEL FOR PERSONALIZED PREDICTION OF RESPONSE TO PEGYLATED-INTERFERON-ALFA AND RIBAVIRIN IN THE TREATMENT OF CHRONIC HEPATITIS C SO HEPATOLOGY LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 29-NOV 02, 2010 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [O'Brien, Thomas R.; Pfeiffer, Ruth] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Everhart, James E.] NIDDK, Div Digest Dis & Nutr, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. [Chung, Raymond T.] Massachusetts Gen Hosp, Gastrointestinal Unit, Med Serv, Boston, MA 02114 USA. [Morgan, Timothy R.] Univ Calif Irvine, Div Gastroenterol, Irvine, CA USA. [Morgan, Timothy R.] VA Long Beach Healthcare Syst, Gastroenterol Serv, Long Beach, CA USA. [Bonkovsky, Herbert L.] Carolinas Med Ctr, Charlotte, NC 28203 USA. [Shao, Yongwu] Informat Management Serv Inc, Silver Spring, MD USA. [Lok, Anna S.] Univ Michigan, Med Ctr, Div Gastroenterol, Ann Arbor, MI USA. [Sninsky, John] Bon Secours Hlth Syst, Liver Inst Virginia, Newport News, VA USA. [Sninsky, John] Celera Corp, Alameda, CA USA. RI Pfeiffer, Ruth /F-4748-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2010 VL 52 IS 4 SU S MA 127 BP 382A EP 382A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 740EY UT WOS:000288775600128 ER PT J AU Noureddin, M Rotman, Y Feld, J Thomas, E Koh, C Abdalla, A Holz, L Park, SH Park, Y Ghany, MG Doo, E Heller, T Rehermann, B Hoofnagle, JH Liang, TJ AF Noureddin, Mazen Rotman, Yaron Feld, Jordan Thomas, Emmanuel Koh, Christopher Abdalla, Adil Holz, Lauren Park, Su-Hyung Park, Yoon Ghany, Marc G. Doo, Edward Heller, Theo Rehermann, Barbara Hoofnagle, Jay H. Liang, T. Jake TI EFFECTS OF RIBAVIRIN MONOTHERAPY ON ALT, HCV VIRAL LEVELS, SERUM CYTOKINES, AND HEPATIC INTERFERON-STIMULATED GENE EXPRESSION IN CHRONIC HEPATITIS C SO HEPATOLOGY LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 29-NOV 02, 2010 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Noureddin, Mazen; Rotman, Yaron; Feld, Jordan; Thomas, Emmanuel; Koh, Christopher; Abdalla, Adil; Holz, Lauren; Park, Su-Hyung; Park, Yoon; Ghany, Marc G.; Doo, Edward; Heller, Theo; Rehermann, Barbara; Hoofnagle, Jay H.; Liang, T. Jake] NIDDK, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2010 VL 52 IS 4 SU S MA 908 BP 756A EP 756A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 740EY UT WOS:000288775601227 ER PT J AU Shah, SR Marcellin, P Foster, GR Manns, MP Patel, K Kottilil, S Pulkstenis, E Subramanian, M Nelson, DR Zeuzem, S AF Shah, Samir R. Marcellin, Patrick Foster, Graham R. Manns, Michael P. Patel, Keyur Kottilil, Shyam Pulkstenis, Erik Subramanian, Mani Nelson, David R. Zeuzem, Stefan TI PREDICTORS OF RELAPSE IN GENOTYPE 3 INFECTED CHRONIC HCV PATIENTS WHO ACHIEVE RAPID VIROLOGIC RESPONSE SO HEPATOLOGY LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 29-NOV 02, 2010 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Shah, Samir R.] Jaslok Hosp & Res Ctr, Mumbai, Maharashtra, India. [Marcellin, Patrick] Breach Candy Hosp, Mumbai, Maharashtra, India. [Marcellin, Patrick] Hop Beaujon, Clichy, France. [Foster, Graham R.] Royal London Hosp, London E1 1BB, England. [Manns, Michael P.] Hannover Med Sch, D-30623 Hannover, Germany. [Patel, Keyur] Duke Univ, Med Ctr, Durham, NC USA. [Patel, Keyur] Duke Clin Res Inst, Durham, NC USA. [Kottilil, Shyam] Natl Inst Allergy & Infect Dis, Bethesda, MD USA. [Pulkstenis, Erik] Human Genome Sci Inc, Rockville, MD USA. [Nelson, David R.] Univ Florida, Gainesville, FL USA. [Zeuzem, Stefan] Klinikum Johann Wolfgang Goethe Univ Hosp, Med Klin 1, Frankfurt, Germany. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2010 VL 52 IS 4 SU S MA 991 BP 799A EP 799A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 740EY UT WOS:000288775601309 ER PT J AU Jeong, WI Park, O Suh, YG Byun, JS Park, SY Kim, JK Ko, H Wang, H Miller, AM Gao, B AF Jeong, Won-Il Park, Ogyi Suh, Yang-gun Byun, Jin-Seok Park, So-Young Kim, Ja Kyung Ko, Hyojin Wang, Hua Miller, Andrew M. Gao, Bin TI SUPPRESSION OF INNATE IMMUNITY (NK CELL/IFN-gamma) IN THE ADVANCED STAGES OF LIVER FIBROSIS IN MICE SO HEPATOLOGY LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 29-NOV 02, 2010 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Jeong, Won-Il; Suh, Yang-gun; Byun, Jin-Seok; Park, So-Young] Korea Adv Inst Sci & Technol, Grad Sch Med Sci & Engn, Taejon 305701, South Korea. [Kim, Ja Kyung] Yonsei Univ, Coll Med, Dept Internal Med, Seoul, South Korea. [Ko, Hyojin] Gwangju Inst Sci & Technol, Kwangju, South Korea. [Jeong, Won-Il; Park, Ogyi; Wang, Hua; Miller, Andrew M.; Gao, Bin] NIAAA, Sect Liver Biol LPS, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2010 VL 52 IS 4 SU S MA 2013 BP 1276A EP 1276A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 740EY UT WOS:000288775602631 ER PT J AU Santoro, N Kursawe, R D'Adamo, E Dykas, DJ Zhang, CK Bale, AE Cali, AM Narayan, D Shaw, MM Pierpont, B Savoye, M Lartaud, D Eldrich, S Cushman, SW Zhao, HY Shulman, GI Caprio, S AF Santoro, Nicola Kursawe, Romy D'Adamo, Ebe Dykas, Daniel J. Zhang, Clarence K. Bale, Allen E. Cali, Anna M. Narayan, Deepak Shaw, Melissa M. Pierpont, Bridget Savoye, Mary Lartaud, Derek Eldrich, Samuel Cushman, Samuel W. Zhao, Hongyu Shulman, Gerald I. Caprio, Sonia TI A Common Variant in the Patatin-Like Phospholipase 3 Gene (PNPLA3) Is Associated with Fatty Liver Disease in Obese Children and Adolescents SO HEPATOLOGY LA English DT Article ID HEPATIC INSULIN-RESISTANCE; MESSENGER-RNA EXPRESSION; HUMAN ADIPOSE-TISSUE; GLUCOSE-TOLERANCE; SENSITIVITY INDEXES; ADIPONUTRIN GENE; FAMILY-MEMBERS; STEATOSIS; MICE; ADIPOCYTES AB The genetic factors associated with susceptibility to nonalcoholic fatty liver disease (NAFLD) in pediatric obesity remain largely unknown. Recently, a nonsynonymous single-nucleotide polymorphism (rs738409), in the patatin-like phospholipase 3 gene (PNPL43) has been associated with hepatic steatosis in adults. In a multiethnic group of 85 obese youths, we genotyped the PNLPA3 single-nucleotide polymorphism, measured hepatic fat content by magnetic resonance imaging and insulin sensitivity by the insulin clamp. Because PNPLA3 might affect adipogenesis/lipogenesis, we explored the putative association with the distribution of adipose cell size and the expression of some adipogenic/lipogenic genes in a subset of subjects who underwent a subcutaneous fat biopsy. Steatosis was present in 41% of Caucasians, 23% of African Americans, and 66% of Hispanics. The frequency of PNPLA3(rs738409) G allele was 0.324 in Caucasians, 0.183 in African Americans, and 0.483 in Hispanics. The prevalence of the G allele was higher in subjects showing hepatic steatosis. Surprisingly, subjects carrying the G allele showed comparable hepatic glucose production rates, peripheral glucose disposal rate, and glycerol turnover as the CC homozygotes. Carriers of the G allele showed smaller adipocytes than those with CC genotype (P = 0.005). Although the expression of PNPLA3, PNPLA2, PPARy.2(peroxisome proliferator-activated receptor gamma 2), SREBPIc(sterol regulatory element binding protein. 1c), and ACACA(acetyl coenzyme A carboxylase) was not different between genotypes, carriers of the G allele showed lower leptin (LEP)(P = 0.03) and sirtuin 1 (SIRT1) expression (P = 0.04). Conclusion: A common variant of the PNPL43 gene confers susceptibility to hepatic steatosis in obese youths without increasing the level of hepatic and peripheral insulin resistance. The rs738409 PNPLA3 G allele is associated with morphological changes in adipocyte cell size. (HEIwrowcy 2010;52:1281-1290) C1 [Santoro, Nicola; Kursawe, Romy; D'Adamo, Ebe; Cali, Anna M.; Shaw, Melissa M.; Pierpont, Bridget; Savoye, Mary; Lartaud, Derek; Eldrich, Samuel; Caprio, Sonia] Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06520 USA. [Dykas, Daniel J.; Bale, Allen E.] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06520 USA. [Narayan, Deepak] Yale Univ, Sch Med, Dept Plast Surg, New Haven, CT 06520 USA. [D'Adamo, Ebe] Univ G dAnnunzio, Dept Pediat, Chieti, Italy. [Zhang, Clarence K.; Zhao, Hongyu] Yale Univ, Ctr Stat Genom & Prote, New Haven, CT 06520 USA. [Shulman, Gerald I.] Howard Hughes Med Inst, Dept Cellular & Mol Physiol, New Haven, CT 06510 USA. [Shulman, Gerald I.] Howard Hughes Med Inst, Dept Internal Med, New Haven, CT 06510 USA. [Cushman, Samuel W.] NIDDK, NIH, Diabet Branch, New Haven, CT USA. RP Caprio, S (reprint author), Yale Univ, Sch Med, Dept Pediat, 330 Cedar St,POB 208064, New Haven, CT 06520 USA. EM sonia.caprio@yale.edu OI Santoro, Nicola/0000-0001-6437-4173 FU National Institutes of Health [R01-HD40787, R01-HD28016, K24-HD01464, R01 DK49230]; CTSA [ULI RR0249139] FX This study was supported by grants from the National Institutes of Health (MN): (R01-HD40787, R01-HD28016, and K24-HD01464 to S.C. R01 DK49230 to G.I.S.), and by CTSA Grant Number ULI RR0249139.fiwni the National Center fir Research Resources (NCRR), a component of NIH; and ROIEB006494 (Bioimage Suite), and Distinguished (finical Scientist Awards from the American Diabetes Association (to S. C). S. WC is supported by the Intramural Research Program of the NIH, NIDDK NR 41 TC 94 Z9 94 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 OCT PY 2010 VL 52 IS 4 BP 1281 EP 1290 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 660BK UT WOS:000282613000015 PM 20803499 ER PT J AU Ki, SH Park, O Zheng, MQ Morales-Ibanez, O Kolls, JK Bataller, R Gao, B AF Ki, Sung Hwan Park, Oygi Zheng, Mingquan Morales-Ibanez, Oriol Kolls, Jay K. Bataller, Ramon Gao, Bin TI Interleukin-22 Treatment Ameliorates Alcoholic Liver Injury in a Murine Model of Chronic-Binge Ethanol Feeding: Role off Signal Transducer and Activator of Transcription 3 SO HEPATOLOGY LA English DT Article ID FATTY LIVER; HEPATIC STEATOSIS; DISEASE; MICE; IL-22; DIET; SENSITIZATION; REGENERATION; HEPATECTOMY; PATHWAYS AB Interleukin-22 (IL-22), a recently identified member of the IL-10 family of cytokines that is produced by Th17 and natural killer cells, plays an important role in controlling bacterial infection, homeostasis, and tissue repair. Here, we tested the effect of IL-22 on alcohol-induced liver injury in a murine model of chronic-binge ethanol feeding. Feeding male C57BL/6 mice with a Lieber-DeCarli diet containing 5% ethanol for 10 days, followed by a single dose of ethanol (5 g/kg body weight) by gavage, induces significant fatty liver and liver injury with peak serum levels of approximately 250 IU/L alanine atninotransferase and 420 IU/L aspartate aminotransferase 9 hours after gavage. Moreover, chronic-binge ethanol administration increases expression of hepatic and serum inflammatory cytokines and hepatic oxidatiNe stress. Using this model, we demonstrate that treatment with IL-22 recombinant protein activates hepatic signal transducer and activator of transcription 3 (STAT3) and ameliorates al coholic fatty liver, liver injury, and hepatic oxidative stress. Administration with IL-22 adenovirus also prevents alcohol-induced steatosis and liver injury. Deletion of STAT3 in hepatocytes abolishes the hepatoprotection provided by IL-22 in alcoholic liver injury. In addition, IL-22 treatment down-regulates the hepatic expression of fatty acid transport protein, but up-regulates several antioxidant, antiapoptotic, and antimicrobial genes. Finally, expression of IL-22 receptor 1 is up-regulated whereas IL-22 is undetectable in the livers from mice with chronic-binge ethanol feeding or patients with alcoholic hepatitis. Conclusion: Chronicbinge ethanol feeding may be a useful model to study the early stages of alcoholic liver injury. IL-22 treatment could be a potential therapeutic option to ameliorate alcoholic liver disease, due to its antioxidant, antiapoptotic, antisteatotic, proliferative, and antimicrobial effects with the added benefit of potentially few side effects. (HEPAT0LOGY 2010;52:1291-1300) C1 [Ki, Sung Hwan; Park, Oygi; Gao, Bin] NIAAA, Lab Liver Dis, NIH, Bethesda, MD 20892 USA. [Ki, Sung Hwan] Chosun Univ, Coll Pharm, Kwangju, South Korea. [Zheng, Mingquan; Kolls, Jay K.] Louisiana State Univ, Hlth Sci Ctr, Dept Genet, New Orleans, LA USA. [Morales-Ibanez, Oriol; Bataller, Ramon] Hosp Clin Barcelona, Liver Unit, Inst Invest Biomed August Pi & Sunyer, Ctr Invest Biomed Red Enfermedades Hepat & Digest, Barcelona, Catalonia, Spain. RP Gao, B (reprint author), NIAAA, Lab Liver Dis, NIH, 5625 Fishers Lane, Bethesda, MD 20892 USA. EM bgao@mail.nih.gov FU NIAAA, NIH FX This work was supported by the intramural program of NIAAA, NIH. NR 37 TC 141 Z9 157 U1 2 U2 19 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2010 VL 52 IS 4 BP 1291 EP 1300 DI 10.1002/hep.23837 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 660BK UT WOS:000282613000016 PM 20842630 ER PT J AU Speliotes, EK Massaro, JM O'Donnell, CJ Fox, CS AF Speliotes, Elizabeth K. Massaro, Joseph M. O'Donnell, Christopher J. Fox, Caroline S. TI Uric Acid Potentially Links Fatty Liver and High Blood Pressure Reply SO HEPATOLOGY LA English DT Letter C1 [Speliotes, Elizabeth K.] Massachusetts Gen Hosp, Dept Gastroenterol, Boston, MA 02114 USA. [O'Donnell, Christopher J.] Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA. [Speliotes, Elizabeth K.] Harvard & Massachusetts Inst technol, Dept Med & Populat Genet, Broad Inst, Cambridge, MA USA. [Speliotes, Elizabeth K.; Massaro, Joseph M.; O'Donnell, Christopher J.; Fox, Caroline S.] NHLBI, Framingham, MA USA. [Speliotes, Elizabeth K.; Massaro, Joseph M.; O'Donnell, Christopher J.; Fox, Caroline S.] Boston Univ, Framingham Heart Study, Framingham, MA USA. [Massaro, Joseph M.] Boston Univ, Dept Biostat, Boston, MA 02215 USA. [Fox, Caroline S.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Fox, Caroline S.] Brigham & Womens Hosp, Dept Endocrinol, Boston, MA 02115 USA. RP Speliotes, EK (reprint author), Massachusetts Gen Hosp, Dept Gastroenterol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 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 OCT PY 2010 VL 52 IS 4 BP 1519 EP 1519 DI 10.1002/hep.23887 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 660BK UT WOS:000282613000044 ER PT J AU Chantry, CJ Cervia, JS Hughes, MD Alvero, C Hodge, J Borum, P Moye, J AF Chantry, C. J. Cervia, J. S. Hughes, M. D. Alvero, C. Hodge, J. Borum, P. Moye, J., Jr. CA PACTG 1010 Team TI Predictors of growth and body composition in HIV-infected children beginning or changing antiretroviral therapy SO HIV MEDICINE LA English DT Article DE antiretroviral therapy; body composition; CD4; children; fat redistribution; growth; HIV; viral load ID HUMAN-IMMUNODEFICIENCY-VIRUS; FAT-FREE MASS; VIRAL LOAD; 1-INFECTED CHILDREN; PROTEASE INHIBITORS; WOMEN; BORN; REDISTRIBUTION; LIPODYSTROPHY; ADOLESCENTS AB Objectives The aim of the study was to describe growth and body composition changes in HIV-positive children after they had initiated or changed antiretroviral therapy (ART) and to correlate these with viral, immune and treatment parameters. Methods Ninety-seven prepubertal HIV-positive children were observed over 48 weeks upon beginning or changing ART. Anthropometry and bioelectrical impedance analysis results were compared with results from the National Health and Nutrition Examination Survey 1999-2002 (NHANES) to generate z-scores and with results for HIV-exposed, uninfected children from the Women and Infants Transmission Study (WITS). Multivariate analysis was used to evaluate associations between growth and body composition and disease parameters. Results All baseline lean and fat mass measures were below those of controls from NHANES. Weight, height and fat free mass (FFM) index (FFM/height2) z-scores increased over time (P=0.004, 0.037 and 0.027, respectively) and the waist:height ratio z-score decreased (P=0.045), but body mass index and per cent body fat z-scores did not change. Measures did not increase more than in uninfected WITS controls. In multivariate analysis, baseline height, mid-thigh circumference and FFM z-scores related to CD4 percentage (P=0.029, P=0.008 and 0.020, respectively) and change in FFM and FFM index z-scores to CD4 percentage increase (P=0.010 and 0.011, respectively). Compared with WITS controls, baseline differences in height and mid-thigh muscle circumference were also associated with CD4 percentage. Case-control differences in change in both subscapular skinfold (SSF) thickness and the SSF:triceps skinfold ratio were inversely associated with viral suppression. No measures related to ART class(es) at baseline or over time. Conclusions In these HIV-positive children, beginning or changing ART was associated with improved growth and lean body mass (LBM), as indicated by FFM index. Height and LBM related to CD4 percentage at baseline and over time. Altered fat distribution and greater central adiposity were associated with detectable virus but not ART class(es) received. C1 [Chantry, C. J.] Univ Calif Davis, Med Ctr, Dept Pediat, Sacramento, CA 95817 USA. [Cervia, J. S.] Albert Einstein Coll Med, Bronx, NY 10467 USA. [Hughes, M. D.; Alvero, C.] Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA. [Hodge, J.] Frontier Sci & Technol Res Fdn Inc, Amherst, NY USA. [Borum, P.] Univ Florida, Gainesville, FL USA. [Moye, J., Jr.] NICHD, NIH, Bethesda, MD USA. RP Chantry, CJ (reprint author), Univ Calif Davis, Med Ctr, Dept Pediat, 2516 Stockton Blvd, Sacramento, CA 95817 USA. EM caroline.chantry@ucdmc.ucdavis.edu OI moye, john/0000-0001-9976-8586 FU Pediatric AIDS Clinical Trials Group of the National Institute of Allergy and Infectious Diseases; Pediatric/Perinatal HIV Clinical Trials Network of the National Institute of Child Health and Human Development, National Institutes of Health, Bethesda MD FX The authors would like to acknowledge the children who participated in this study and their families, the entire protocol 1010 team for their contributions and support and Jie Chin for statistical support. We are also grateful to the Women and Infant Transmission Study for sharing data on matched, uninfected children. This study was supported in part by the Pediatric AIDS Clinical Trials Group of the National Institute of Allergy and Infectious Diseases and the Pediatric/Perinatal HIV Clinical Trials Network of the National Institute of Child Health and Human Development, National Institutes of Health, Bethesda MD. The following sites and individuals have contributed to this study: Howard University: S. Rana, P. Yu, S. Dangol, J. Roa; Bronx Lebanon Hospital Center; St. Jude Children's Hospital: M. Donohoe, K. Knapp, N. Patel, J. Utech; Baylor Texas Children's Hospital: K. Owl, M. Dobmeier, M. Paul, C. Hanson; Children's Hospital of Boston; Harlem Hospital: E. Abrams, D. Calo, M. Fere, S. Champion; North Broward Hospital District; Jacobi Medical Center: A. Wiznia, M. Chin, K. Dorio, J. Abadi; University of Florida: J. Sleasman, R. Lawrence, C. Delany; Children's Hospital LA: T. Dunaway, L. Heller; University of Maryland: J. Farley, M. MacFadden; State University of New York at Stony Brook: S. Nachman, M. Davi, C. Seifert, S. Muniz; Metropolitan Hospital Center: M. Bamji, I. Pathak, S. Manwani; Children's Hospital, Oakland: A. Petru, T. Courville, K. Gold, S. Bessler; Harbor-UCLA Medical Center: M. Keller, K. Zangwill, J. Hayes, A. Gagajena; Columbia Presbyterian Medical Center: A. Higgins, M. Foca; University of Miami: C. Goldberg, M. Bissainthe, C. Mitchell, G. Scott; New York University School of Medicine: T. Hastings, M. Mintor, N. Deygoo, W. Borkowsky; University of Illinois: K. Rich; K. Hayani, J. Camacho; Children's Hospital University of Colorado, Denver: E. McFarland, M. Levin, C. Salbenblatt, E. Barr; Medical College of Georgia: W. Foshee, C. Mani, C. White, B. Kiernan; Johns Hopkins University: S. Marvin, A. Ruff; Duke University: R. McKinney, Y. Choi, L. Ferguson, J. Swetnam; Children's National Medical Center; San Juan City Hospital: M. Acevedo, M. Gonzales, C. Martinez Betancoult, F. Pabon; Yale University School of Medicine: D. Schroeder, S. Romano, M.J. Aquino-de Jesus; Los Angeles County Medical Center: J. Homans, Y. Rodriquez, A. Kovacs; University of Puerto Rico: I. Febo Rodriquez, L. Lugo, I. Heyer, C. Martinez; University of Massachusetts Medical School: K. Luzuriaga. NR 30 TC 6 Z9 6 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1464-2662 J9 HIV MED JI HIV Med. PD OCT PY 2010 VL 11 IS 9 BP 573 EP 583 DI 10.1111/j.1468-1293.2010.00823.x PG 11 WC Infectious Diseases SC Infectious Diseases GA 647WU UT WOS:000281652100004 PM 20345880 ER PT J AU Lock, M McGorray, S Auricchio, A Ayuso, E Beecham, EJ Blouin-Tavel, V Bosch, F Bose, M Byrne, BJ Caton, T Chiorini, JA Chtarto, A Clark, KR Conlon, T Darmon, C Doria, M Douar, A Flotte, TR Francis, JD Francois, A Giacca, M Korn, MT Korytov, I Leon, X Leuchs, B Lux, G Melas, C Mizukami, H Moullier, P Muller, M Ozawa, K Philipsberg, T Poulard, K Raupp, C Riviere, C Roosendaal, SD Samulski, RJ Soltys, SM Surosky, R Tenenbau, L Thomas, DL van Montfort, B Veres, G Wright, JF Xu, YL Zelenaia, O Zentilin, L Snyder, RO AF Lock, Martin McGorray, Susan Auricchio, Alberto Ayuso, Eduard Beecham, E. Jeffrey Blouin-Tavel, Veronique Bosch, Fatima Bose, Mahuya Byrne, Barry J. Caton, Tina Chiorini, John A. Chtarto, Abdelwahed Clark, K. Reed Conlon, Thomas Darmon, Christophe Doria, Monica Douar, Anne Flotte, Terence R. Francis, Joyce D. Francois, Achille Giacca, Mauro Korn, Michael T. Korytov, Irina Leon, Xavier Leuchs, Barbara Lux, Gabriele Melas, Catherine Mizukami, Hiroaki Moullier, Philippe Mueller, Marcus Ozawa, Keiya Philipsberg, Tina Poulard, Karine Raupp, Christina Riviere, Christel Roosendaal, Sigrid D. Samulski, R. Jude Soltys, Steven M. Surosky, Richard Tenenbau, Liliane Thomas, Darby L. van Montfort, Bart Veres, Gabor Wright, J. Fraser Xu, Yili Zelenaia, Olga Zentilin, Lorena Snyder, Richard O. TI Characterization of a Recombinant Adeno-Associated Virus Type 2 Reference Standard Material SO HUMAN GENE THERAPY LA English DT Article ID GENE-THERAPY; VIRAL VECTORS; PURIFICATION; SEROTYPE-2; CAPSIDS; TRIAL AB A recombinant adeno-associated virus serotype 2 Reference Standard Material (rAAV2 RSM) has been produced and characterized with the purpose of providing a reference standard for particle titer, vector genome titer, and infectious titer for AAV2 gene transfer vectors. Production and purification of the reference material were carried out by helper virus-free transient transfection and chromatographic purification. The purified bulk material was vialed, confirmed negative for microbial contamination, and then distributed for characterization along with standard assay protocols and assay reagents to 16 laboratories worldwide. Using statistical transformation and modeling of the raw data, mean titers and confidence intervals were determined for capsid particles ({X}, 9.18 x 10(11) particles/ml; 95% confidence interval [CI], 7.89 x 10(11) to 1.05 x 10(12) particles/ml), vector genomes ({X}, 3.28 x 10(10) vector genomes/ml; 95% CI, 2.70 x 10(10) to 4.75 x 10(10) vector genomes/ml), transducing units ({X}, 5.09 x 10(8) transducing units/ml; 95% CI, 2.00 x 10(8) to 9.60 x 10(8) transducing units/ml), and infectious units ({X}, 4.37 x 10(9) TCID(50) IU/ml; 95% CI, 2.06 x 10(9) to 9.26 x 10(9) TCID(50) IU/ml). Further analysis confirmed the identity of the reference material as AAV2 and the purity relative to nonvector proteins as greater than 94%. One obvious trend in the quantitative data was the degree of variation between institutions for each assay despite the relatively tight correlation of assay results within an institution. This relatively poor degree of interlaboratory precision and accuracy was apparent even though attempts were made to standardize the assays by providing detailed protocols and common reagents. This is the first time that such variation between laboratories has been thoroughly documented and the findings emphasize the need in the field for universal reference standards. The rAAV2 RSM has been deposited with the American Type Culture Collection and is available to the scientific community to calibrate laboratory-specific internal titer standards. Anticipated uses of the rAAV2 RSM are discussed. C1 [Snyder, Richard O.] Univ Florida, Coll Med, Dept Mol Genet & Microbiol, Gainesville, FL 32610 USA. [Lock, Martin; Korn, Michael T.] Univ Penn, Dept Pathol & Lab Med, Gene Therapy Program, Philadelphia, PA 19104 USA. [McGorray, Susan] Univ Florida, Coll Med, Dept Epidemiol & Hlth Policy Res, Gainesville, FL 32610 USA. [Auricchio, Alberto] Univ Naples Federico 2, Dept Pediat, I-80131 Naples, Italy. [Auricchio, Alberto; Doria, Monica] Telethon Inst Genet & Med TIGEM, I-80131 Naples, Italy. [Ayuso, Eduard; Bosch, Fatima; Leon, Xavier] Univ Autonoma Barcelona, Sch Vet Med, Ctr Anim Biotechnol & Gene Therapy, Bellaterra 08193, Spain. [Ayuso, Eduard; Bosch, Fatima; Leon, Xavier] Univ Autonoma Barcelona, Sch Vet Med, Dept Biochem & Mol Biol, Bellaterra 08193, Spain. [Beecham, E. Jeffrey; Samulski, R. Jude; Soltys, Steven M.] Univ N Carolina, Gene Therapy Ctr, Chapel Hill, NC 27599 USA. [Blouin-Tavel, Veronique; Darmon, Christophe; Francois, Achille; Moullier, Philippe] CHU Nantes, INSERM, UMR649, F-44007 Nantes, France. [Bose, Mahuya; Caton, Tina; Francis, Joyce D.; Snyder, Richard O.] Univ Florida, Ctr Excellence Regenerat Hlth Biotechnol, Gainesville, FL 32611 USA. [Byrne, Barry J.; Snyder, Richard O.] Univ Florida, Dept Pediat, Div Cellular & Mol Therapy, Gainesville, FL 32610 USA. [Byrne, Barry J.; Conlon, Thomas; Korytov, Irina; Philipsberg, Tina] Univ Florida, Powell Gene Therapy Ctr Vector Core, Gainesville, FL 32611 USA. [Chiorini, John A.] Natl Inst Dent & Craniofacial Res, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD 20892 USA. [Chtarto, Abdelwahed; Melas, Catherine; Tenenbau, Liliane] Free Univ Brussels, Lab Expt Neurosurg, B-1070 Brussels, Belgium. [Chtarto, Abdelwahed; Melas, Catherine; Tenenbau, Liliane] Free Univ Brussels, Multidisciplinary Res Inst, B-1070 Brussels, Belgium. [Clark, K. Reed] Nationwide Childrens Hosp, Res Inst, Ctr Gene Therapy, Columbus, OH 43205 USA. [Clark, K. Reed] Ohio State Univ, Dept Pediat, Columbus, OH 43210 USA. [Douar, Anne; Poulard, Karine; Riviere, Christel] Genethon, F-91000 Evry, France. [Flotte, Terence R.] Univ Massachusetts, Sch Med, Gene Therapy Ctr, Worcester, MA 01655 USA. [Flotte, Terence R.] Univ Massachusetts, Dept Pediat, Worcester, MA 01655 USA. [Giacca, Mauro; Zentilin, Lorena] ICGEB, Mol Med Lab, I-34149 Trieste, Italy. [Leuchs, Barbara; Mueller, Marcus; Raupp, Christina] German Canc Res Ctr, Infect & Canc Program, D-69120 Heidelberg, Germany. [Lux, Gabriele] Pharmazeut Fabrik Dr Reckeweg, D-64625 Bensheim, Germany. [Mizukami, Hiroaki; Ozawa, Keiya] Jichi Med Univ, Ctr Mol Med, Div Genet Therapeut, Shimotsuke 3290498, Japan. [Roosendaal, Sigrid D.; van Montfort, Bart] Amsterdam Mol Therapeut, NL-1100 Amsterdam, Netherlands. [Surosky, Richard; Xu, Yili] Sangamo BioSci, Richmond, CA 94804 USA. [Thomas, Darby L.; Veres, Gabor] Appl Genet Technol, Alachua, FL 32615 USA. [Wright, J. Fraser; Zelenaia, Olga] Childrens Hosp Philadelphia, Ctr Cellular & Mol Therapeut, Philadelphia, PA 19104 USA. [Wright, J. Fraser] Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. RP Snyder, RO (reprint author), Univ Florida, Coll Med, Dept Mol Genet & Microbiol, 1600 SW Archer Rd, Gainesville, FL 32610 USA. EM rsnyder@cerhb.ufl.edu RI Clark, Kelly/E-2900-2011; Mizukami, Hiroaki/D-7674-2013; Giacca, Mauro/J-9287-2016; Tenenbaum, Liliane/O-5917-2016; OI BOSCH, FATIMA/0000-0002-7705-5515; Mizukami, Hiroaki/0000-0001-8954-874X; Giacca, Mauro/0000-0003-2927-7225; Tenenbaum, Liliane/0000-0003-4619-9660; AURICCHIO, Alberto/0000-0002-0832-2472 FU NIH [P30-DK-047757, U42RR11148]; Fondazione Telethon FX Current and former members of the Executive Committee: Denise Gavin-FDA (nonvoting member); Daniel Rosenblum-NIH NCRR (nonvoting member); Keith Carson-International Society for BioProcess Technology; Parris Burd-Bayer Corporation; Olivier Danos-Genethon; Maritza McIntyre-FDA (nonvoting member); Richard Knazek-NIH NCRR (nonvoting member). Manufacturing committee: Guang Ping Gao-University of Pennsylvania; Philip Cross-Harvard Medical School; Anna Salvetti-CHU Hotel Dieu, Nantes, France; Sue Washer-Applied Genetic Technologies; Guang Qu-Avigen. Quality committee: Marie Printz-Ceregene; Paul Husak-Cell Genesys; Scott McPhee-Thomas Jefferson University; Jurg Sommer-Avigen; Jim Marich-Cell Genesys. We acknowledge the technical help of the following during the testing phase: Mark Potter-PGTC Vector Core; Gitte Kitlen-PGTC Quality Control; Lynn Combee-PGTC Toxicology Core; Cheryl Roberts-PGTC Toxicology Core; Tanja Finnas-AMT; Martha Hoekstra-AMT. We are grateful to James Wilson-University of Pennsylvania for supporting the beta testing through NIH grant P30-DK-047757 and an SRA from GlaxoSmithKline. We are also indebted to Peggy Fahnestock and Liz Kerrigan at the ATCC for coordinating the distribution of materials to testing laboratories. This work was supported by NIH grant U42RR11148. We acknowledge the generosity of the ATCC, Nunc, Aldevron, Corning, Fisher Thermo Scientific, the Indiana University Vector Production Facility, HyClone, Mediatech, Progen, and the Williamsburg Bioprocessing Foundation. Richard Surosky is employed by a company that may have interest in these vectors for therapeutic purposes. Richard Snyder owns equity in a gene therapy company that is commercializing AAV for gene therapy applications. NR 26 TC 41 Z9 42 U1 1 U2 7 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD OCT PY 2010 VL 21 IS 10 BP 1273 EP 1285 DI 10.1089/hum.2009.223 PG 13 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 664JF UT WOS:000282955500006 PM 20486768 ER PT J AU Morgan, R AF Morgan, R. TI Cancer immunotherapy with genetically modified lymphocytes SO HUMAN GENE THERAPY LA English DT Meeting Abstract CT 18th Annual Congress of the European-Society-of-Gene-and-Cell-Therapy CY OCT 22-25, 2010 CL Milan, ITALY C1 [Morgan, R.] NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD OCT PY 2010 VL 21 IS 10 BP 1358 EP 1359 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 664JF UT WOS:000282955500017 ER PT J AU Donsante, A Yi, L Zerfas, P Brinster, L Sullivan, P Goldstein, D Prohaska, J Centeno, J Kaler, SG AF Donsante, A. Yi, L. Zerfas, P. Brinster, L. Sullivan, P. Goldstein, D. Prohaska, J. Centeno, J. Kaler, S. G. TI Transduction of choroid plexus epithelia is crucial for gene therapy rescue in a murine model of Menkes disease SO HUMAN GENE THERAPY LA English DT Meeting Abstract CT 18th Annual Congress of the European-Society-of-Gene-and-Cell-Therapy CY OCT 22-25, 2010 CL Milan, ITALY C1 [Donsante, A.; Yi, L.; Kaler, S. G.] NICHD, Program Mol Med, NIH, Bethesda, MD 20892 USA. [Brinster, L.] NIH, Div Vet Resources, Off Res Serv, OD, Bethesda, MD 20892 USA. [Sullivan, P.; Goldstein, D.] NINDS, Clin Neurocardiol Sect, NIH, Bethesda, MD 20892 USA. [Prohaska, J.] Univ Minnesota, Dept Biochem & Mol Biol, Duluth, MN 55812 USA. [Centeno, J.] US Armed Forces Inst Pathol, Div Biophys Toxicol, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD OCT PY 2010 VL 21 IS 10 BP 1425 EP 1426 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 664JF UT WOS:000282955500200 ER PT J AU Chandler, RJ Chandrasekaran, S Venditti, CP AF Chandler, R. J. Chandrasekaran, S. Venditti, C. P. TI AAV8 Gene Transfer Rescues a Neonatal Lethal Murine Model of Proprionic Acidemia SO HUMAN GENE THERAPY LA English DT Meeting Abstract CT 18th Annual Congress of the European-Society-of-Gene-and-Cell-Therapy CY OCT 22-25, 2010 CL Milan, ITALY C1 [Chandler, R. J.; Chandrasekaran, S.; Venditti, C. P.] NHGRI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD OCT PY 2010 VL 21 IS 10 BP 1456 EP 1456 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 664JF UT WOS:000282955500282 ER PT J AU Raza, MH Riazuddin, S Drayna, D AF Raza, Muhammad Hashim Riazuddin, Sheikh Drayna, Dennis TI Identification of an autosomal recessive stuttering locus on chromosome 3q13.2-3q13.33 SO HUMAN GENETICS LA English DT Article ID LINKAGE AB Stuttering is a common speech disorder with substantial genetic contributions. To better understand the genetic factors involved in stuttering, we performed a genome-wide linkage study in a newly-ascertained consanguineous stuttering family from Pakistan. A linkage scan in this family using parametric linkage analysis revealed significant linkage only on chromosome 3q13.2-3q13.33, with a maximum two-point LOD score of 4.23 under an autosomal recessive model of inheritance. C1 [Drayna, Dennis] NIDCD, NIH, Rockville, MD 20850 USA. [Raza, Muhammad Hashim; Drayna, Dennis] Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD USA. [Raza, Muhammad Hashim; Riazuddin, Sheikh] Univ Punjab, Ctr Excellence Mol Biol, Lahore, Pakistan. RP Drayna, D (reprint author), NIDCD, NIH, 5 Res Court, Rockville, MD 20850 USA. EM drayna@nidcd.nih.gov NR 7 TC 15 Z9 18 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD OCT PY 2010 VL 128 IS 4 BP 461 EP 463 DI 10.1007/s00439-010-0871-y PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 650OK UT WOS:000281858700011 PM 20706738 ER PT J AU Chi, ZL Yasumoto, F Sergeev, Y Minami, M Obazawa, M Kimura, I Takada, Y Iwata, T AF Chi, Zai-Long Yasumoto, Fumie Sergeev, Yuri Minami, Masayoshi Obazawa, Minoru Kimura, Itaru Takada, Yuichiro Iwata, Takeshi TI Mutant WDR36 directly affects axon growth of retinal ganglion cells leading to progressive retinal degeneration in mice SO HUMAN MOLECULAR GENETICS LA English DT Article ID OPEN-ANGLE GLAUCOMA; NORMAL-TENSION GLAUCOMA; DNA-SEQUENCE VARIANTS; DBA/2J MICE; TRANSGENIC MICE; GERMAN PATIENTS; IRIS ATROPHY; GENE; IDENTIFICATION; MUTATIONS AB Primary open-angle glaucoma (POAG) is one of the three principal subtypes of glaucoma and among the leading cause of blindness worldwide. POAG is defined by cell death of the retinal ganglion cells (RGCs) and surrounding neuronal cells at higher or normal intraocular pressure (IOP). Coded by one of the three genes responsible for POAG, WD repeat-containing protein 36 (WDR36) has two domains with a similar folding. To address whether WDR36 is functionally important in the retina, we developed four transgenic mice strains overexpressing a wild-type (Wt) and three mutant variants of D606G, deletion of amino acids at positions 605-607 (Del605-607) and at 601-640 (Del601-640) equivalent to the location of the D658G mutation observed in POAG patients. A triple amino acid deletion of mouse Wdr36 at positions 605-607 corresponding to the deletion at positions 657-659 in humans developed progressive retinal degeneration at the peripheral retina with normal IOP. RGCs and connecting amacrine cell synapses were affected at the peripheral retina. Axon outgrowth rate of cultured RGC directly isolated from transgenic animal was significantly reduced by the Wdr36 mutation compared with Wt. Molecular modeling of wild and mutant mouse Wdr36 revealed that deletion at positions 605-607 removed three residues and a hydrogen bond, required to stabilize anti-parallel beta-sheet of the 6th beta-propeller in the second domain. We concluded that WDR36 plays an important functional role in the retina homeostasis and mutation to this gene can cause devastating retinal damage. These data will improve understanding of the functional property of WDR36 in the retina and provide a new animal model for glaucoma therapeutics. C1 [Chi, Zai-Long; Yasumoto, Fumie; Minami, Masayoshi; Obazawa, Minoru; Kimura, Itaru; Takada, Yuichiro; Iwata, Takeshi] Natl Hosp Org, Natl Inst Sensory Organs, Tokyo Med Ctr, Div Mol & Cellular Biol,Meguro Ku, Tokyo 1528902, Japan. [Sergeev, Yuri] NEI, NIH, Ophthalm Genet & Visual Funct Branch, Bethesda, MD 20892 USA. RP Iwata, T (reprint author), Natl Hosp Org, Natl Inst Sensory Organs, Tokyo Med Ctr, Div Mol & Cellular Biol,Meguro Ku, 2-5-1 Higashigaoka, Tokyo 1528902, Japan. EM iwatatakeshi@kankakuki.go.jp FU Japan Ministry of Health, Labour, and Welfare; Japan Ministry of Education, Culture, Sports, Science and Technology; Ministry of Health, Labour, and Welfare of Japan; Ministry of Education, Culture, Sports, Science and Technology of Japan FX This research was supported in part by the grants to T. I. by the Japan Ministry of Health, Labour, and Welfare, the Japan Ministry of Education, Culture, Sports, Science and Technology and Grant-in-Aid for JSPS fellows for Z.-L.C. Funding to pay the Open Access Charge was provided by the Ministry of Health, Labour, and Welfare of Japan and the Ministry of Education, Culture, Sports, Science and Technology of Japan. NR 33 TC 19 Z9 19 U1 1 U2 6 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 OCT PY 2010 VL 19 IS 19 BP 3806 EP 3815 DI 10.1093/hmg/ddq299 PG 10 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 648UD UT WOS:000281718900010 PM 20631153 ER PT J AU Uhrigshardt, H Singh, A Kovtunovych, G Ghosh, M Rouault, TA AF Uhrigshardt, Helge Singh, Anamika Kovtunovych, Gennadiy Ghosh, Manik Rouault, Tracey A. TI Characterization of the human HSC20, an unusual DnaJ type III protein, involved in iron-sulfur cluster biogenesis SO HUMAN MOLECULAR GENETICS LA English DT Article ID ESCHERICHIA-COLI; SCAFFOLD PROTEIN; SACCHAROMYCES-CEREVISIAE; REGULATORY PROTEIN-1; MITOCHONDRIAL HSP70; CHAPERONE SYSTEM; 4FE-4S CLUSTER; HUMAN-CELLS; ISCU; HOMEOSTASIS AB The importance of mitochondrial iron-sulfur cluster (ISC) biogenesis for human health has been well established, but the roles of some components of this critical pathway still remain uncharacterized in mammals. Among them is human heat shock cognate protein 20 (hHSC20), the putative human homolog of the specialized DnaJ type co-chaperones, which are crucial for bacterial and fungal ISC assembly. Here, we show that the human HSC20 protein can complement for its counterpart in yeast, Jac1p, and interacts with its proposed human partners, hISCU and hHSPA9. hHSC20 is expressed in various human tissues and localizes mainly to the mitochondria in HeLa cells. However, small amounts were also detected extra-mitochondrially. RNA interference-mediated depletion of hHSC20 specifically reduced the activities of both mitochondrial and cytosolic ISC-containing enzymes. The recovery of inactivated ISC enzymes was markedly delayed after an oxidative insult of hHSC20-deficient cells. Conversely, overexpression of hHSC20 substantially protected cells from oxidative insults. These results imply that hHSC20 is an integral component of the human ISC biosynthetic machinery that is particularly important in the assembly of ISCs under conditions of oxidative stress. A cysteine-rich N-terminal domain, which clearly distinguishes hHSC20 from the specialized DnaJ type III proteins of fungi and most bacteria, was found to be important for the integrity and function of the human co-chaperone. C1 [Uhrigshardt, Helge; Singh, Anamika; Kovtunovych, Gennadiy; Ghosh, Manik; Rouault, Tracey A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Mol Med, NIH, Bethesda, MD 20892 USA. [Uhrigshardt, Helge] Johns Hopkins Univ, Sch Med, JHU Bayview Prote Ctr, Baltimore, MD 21224 USA. RP Rouault, TA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Mol Med, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM rouault@mail.nih.gov FU Eunice Kennedy Shriver National Institute of Child Health and Human Development FX This work was supported by the intramural program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. NR 95 TC 31 Z9 35 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 EI 1460-2083 J9 HUM MOL GENET JI Hum. Mol. Genet. PD OCT PY 2010 VL 19 IS 19 BP 3816 EP 3834 DI 10.1093/hmg/ddq301 PG 19 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 648UD UT WOS:000281718900011 PM 20668094 ER PT J AU Johanneson, B McDonnell, SK Karyadi, DM Quignon, P McIntosh, L Riska, SM FitzGerald, LM Johnson, G Deutsch, K Williams, G Tillmans, LS Stanford, JL Schaid, DJ Thibodeau, SN Ostrander, EA AF Johanneson, Bo McDonnell, Shannon K. Karyadi, Danielle M. Quignon, Pascale McIntosh, Laura Riska, Shaun M. FitzGerald, Liesel M. Johnson, Gregory Deutsch, Kerry Williams, Gabrielle Tillmans, Lori S. Stanford, Janet L. Schaid, Daniel J. Thibodeau, Stephen N. Ostrander, Elaine A. TI Family-based association analysis of 42 hereditary prostate cancer families identifies the Apolipoprotein L3 region on chromosome 22q12 as a risk locus SO HUMAN MOLECULAR GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY GENES; INTERNATIONAL CONSORTIUM; LINKAGE; SCAN; PEDIGREES; GENETICS; APOPTOSIS; VARIANTS; DISEASE AB Multiple genome-wide scans for hereditary prostate cancer (HPC) have identified susceptibility loci on nearly every chromosome. However, few results have been replicated with statistical significance. One exception is chromosome 22q, for which five independent linkage studies yielded strong evidence for a susceptibility locus in HPC families. Previously, we refined this region to a 2.53 Mb interval, using recombination mapping in 42 linked pedigrees. We now refine this locus to a 15 kb interval, spanning Apolipoprotein L3 (APOL3), using family-based association analyses of 150 total prostate cancer (PC) cases from two independent family collections with 506 unrelated population controls. Analysis of the two independent sets of PC cases highlighted single nucleotide polymorphisms (SNPs) within the APOL3 locus showing the strongest associations with HPC risk, with the most robust results observed when all 150 cases were combined. Analysis of 15 tagSNPs across the 5' end of the locus identified six SNPs with P-values < 2 x 10(-4). The two independent sets of HPC cases highlight the same 15 kb interval at the 5' end of the APOL3 gene and provide strong evidence that SNPs within this 15 kb interval, or in strong linkage disequilibrium with it, contribute to HPC risk. Further analyses of this locus in an independent population-based, case-control study revealed an association between an SNP within the APOL3 locus and PC risk, which was not confirmed in the Cancer Genetic Markers of Susceptibility data set. This study further characterizes the 22q locus in HPC risk and suggests that the role of this region in sporadic PC warrants additional studies. C1 [Johanneson, Bo; Karyadi, Danielle M.; Quignon, Pascale; Johnson, Gregory; Williams, Gabrielle; Ostrander, Elaine A.] NHGRI, NIH, Bethesda, MD 20892 USA. [McDonnell, Shannon K.; Riska, Shaun M.; Schaid, Daniel J.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN 55905 USA. [McIntosh, Laura; FitzGerald, Liesel M.; Stanford, Janet L.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA. [Deutsch, Kerry] Inst Syst Biol, Seattle, WA 98103 USA. [Stanford, Janet L.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. [Tillmans, Lori S.; Thibodeau, Stephen N.] Mayo Clin, Coll Med, Dept Lab Med, Rochester, MN 55905 USA. [Tillmans, Lori S.; Thibodeau, Stephen N.] Mayo Clin, Coll Med, Dept Pathol, Rochester, MN 55905 USA. RP Ostrander, EA (reprint author), NHGRI, NIH, 50 S Dr,Bldg 50,Room 5351, Bethesda, MD 20892 USA. EM eostrand@mail.nih.gov OI Ostrander, Elaine/0000-0001-6075-9738 FU US Public Health Service, National Institutes of Health [RO1 CA080122, RO1 CA056678, RO1 CA092579, P50 CA097186, RO1 CA72818]; National Institutes of Health [N01-HG-65403] FX This work was supported by the US Public Health Service, National Institutes of Health grants [RO1 CA080122, RO1 CA056678, RO1 CA092579 to J.L.S.], [P50 CA097186 supports L. M. F.] and [RO1 CA72818 to S.N.T. and D.J.S.]. PROGRESS investigators also acknowledge additional support from the Prostate Cancer Foundation and the Fred Hutchinson Cancer Research Center. Mayo Clinic investigators [S.N.T., S. K. M., S. M. R., D.J.S.] acknowledge additional support from the Ralph C. Wilson Medical Research Foundation. E.A.O., B.J., D.M.K., P.Q., G.J. and G.W. acknowledge support from the Intramural Program of the National Institutes of Health. Genotyping services were provided by the Center for Inherited Disease Research (CIDR). CIDR is fully funded through a federal contract from the National Institutes of Health to The Johns Hopkins University, Contract Number N01-HG-65403. NR 45 TC 8 Z9 8 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD OCT PY 2010 VL 19 IS 19 BP 3852 EP 3862 DI 10.1093/hmg/ddq283 PG 11 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 648UD UT WOS:000281718900014 PM 20631155 ER PT J AU Canzian, F Cox, DG Setiawan, VW Stram, DO Ziegler, RG Dossus, L Beckmann, L Blanche, H Barricarte, A Berg, CD Bingham, S Buring, J Buys, SS Calle, EE Chanock, SJ Clavel-Chapelon, F DeLancey, JOL Diver, WR Dorronsoro, M Haiman, CA Hallmans, G Hankinson, SE Hunter, DJ Husing, A Isaacs, C Khaw, KT Kolonel, LN Kraft, P Le Marchand, L Lund, E Overvad, K Panico, S Peeters, PHM Pollak, M Thun, MJ Tjonneland, A Trichopoulos, D Tumino, R Yeager, M Hoover, RN Riboli, E Thomas, G Henderson, BE Kaaks, R Feigelson, HS AF Canzian, Federico Cox, David G. Setiawan, V. Wendy Stram, Daniel O. Ziegler, Regina G. Dossus, Laure Beckmann, Lars Blanche, Helene Barricarte, Aurelio Berg, Christine D. Bingham, Sheila Buring, Julie Buys, Saundra S. Calle, Eugenia E. Chanock, Stephen J. Clavel-Chapelon, Francoise DeLancey, John Oliver L. Diver, W. Ryan Dorronsoro, Miren Haiman, Christopher A. Hallmans, Goeran Hankinson, Susan E. Hunter, David J. Huesing, Anika Isaacs, Claudine Khaw, Kay-Tee Kolonel, Laurence N. Kraft, Peter Le Marchand, Loic Lund, Eiliv Overvad, Kim Panico, Salvatore Peeters, Petra H. M. Pollak, Michael Thun, Michael J. Tjonneland, Anne Trichopoulos, Dimitrios Tumino, Rosario Yeager, Meredith Hoover, Robert N. Riboli, Elio Thomas, Gilles Henderson, Brian E. Kaaks, Rudolf Feigelson, Heather Spencer TI Comprehensive analysis of common genetic variation in 61 genes related to steroid hormone and insulin-like growth factor-I metabolism and breast cancer risk in the NCI breast and prostate cancer cohort consortium SO HUMAN MOLECULAR GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; BASE-LINE CHARACTERISTICS; ESTROGEN PLUS PROGESTIN; POSTMENOPAUSAL WOMEN; CIRCULATING LEVELS; IGF-I; MULTIETHNIC COHORT; BINDING-PROTEINS; DEHYDROEPIANDROSTERONE-SULFATE; CONFER SUSCEPTIBILITY AB There is extensive evidence that increases in blood and tissue concentrations of steroid hormones and of insulin-like growth factor I (IGF-I) are associated with breast cancer risk. However, studies of common variation in genes involved in steroid hormone and IGF-I metabolism have yet to provide convincing evidence that such variants predict breast cancer risk. The Breast and Prostate Cancer Cohort Consortium (BPC3) is a collaboration of large US and European cohorts. We genotyped 1416 tagging single nucleotide polymorphisms (SNPs) in 37 steroid hormone metabolism genes and 24 IGF-I pathway genes in 6292 cases of breast cancer and 8135 controls, mostly Caucasian, postmenopausal women from the BPC3. We also imputed 3921 additional SNPs in the regions of interest. None of the SNPs tested was significantly associated with breast cancer risk, after correction for multiple comparisons. The results remained null when cases and controls were stratified by age at diagnosis/recruitment, advanced or nonadvanced disease, body mass index, with or without in situ cases; or restricted to Caucasians. Among 770 estrogen receptor-negative cases, an SNP located 3' of growth hormone receptor (GHR) was marginally associated with increased risk after correction for multiple testing (P-trend = 1.5 x 10(-4)). We found no significant overall associations between breast cancer and common germline variation in 61 genes involved in steroid hormone and IGF-I metabolism in this large, comprehensive study. Although previous studies have shown that variations in these genes can influence endogenous hormone levels, the magnitude of the effect of single SNPs does not appear to be sufficient to alter breast cancer risk. C1 [Canzian, Federico; Dossus, Laure; Beckmann, Lars; Huesing, Anika; Kaaks, Rudolf] German Canc Res Ctr, D-69120 Heidelberg, Germany. [Cox, David G.; Hunter, David J.; Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Cox, David G.] Ctr Leon Berard, INSERM U590, Lyon, France. [Cox, David G.; Riboli, Elio] Imperial Coll, Fac Med, Sch Publ Hlth, London, England. [Setiawan, V. Wendy; Stram, Daniel O.; Haiman, Christopher A.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA. [Ziegler, Regina G.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Berg, Christine D.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. [Blanche, Helene] Fdn Jean Dausset CEPH, Biol Resource Ctr, Paris, France. [Barricarte, Aurelio] Publ Hlth Inst Navarra, Pamplona, Spain. [Bingham, Sheila; Khaw, Kay-Tee] Univ Cambridge, Sch Clin Med, Inst Publ Hlth, Dept Publ Hlth & Primary Care, Cambridge, England. [Buring, Julie; Hankinson, Susan E.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. [Buring, Julie; Hankinson, Susan E.] Harvard Univ, Sch Med, Boston, MA USA. [Buys, Saundra S.; Feigelson, Heather Spencer] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. [Calle, Eugenia E.; DeLancey, John Oliver L.; Diver, W. Ryan; Thun, Michael J.] Amer Canc Soc, Dept Epidemiol, Atlanta, GA 30329 USA. [Clavel-Chapelon, Francoise] Inst Gustave Roussy, Villejuif, France. [Dorronsoro, Miren] Dept Publ Hlth Guipuzcoa, San Sebastian, Spain. [Hallmans, Goeran] Umea Univ, Umea, Sweden. [Isaacs, Claudine] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA. [Kolonel, Laurence N.; Le Marchand, Loic] Univ Hawaii, Canc Res Ctr, Honolulu, HI 96813 USA. [Lund, Eiliv] Univ Tromso, Inst Community Med, Tromso, Norway. [Overvad, Kim] Aarhus Univ Hosp, Aalborg, Denmark. [Panico, Salvatore] Univ Naples Federico II, Naples, Italy. [Peeters, Petra H. M.] Univ Med Ctr, Julius Ctr, Utrecht, Netherlands. [Pollak, Michael] McGill Univ, Dept Oncol, Montreal, PQ, Canada. [Tjonneland, Anne] Danish Canc Soc, Inst Canc Epidemiol, Copenhagen, Denmark. [Trichopoulos, Dimitrios] Acad Athens, Bur Epidemiol Res, Athens, Greece. [Tumino, Rosario] Civile MP Arezzo Hosp, Dept Oncol, Canc Regis & Histopathol Unit, Ragusa, Italy. [Yeager, Meredith] SAIC Frederick Inc, Core Genotyping Facil, Adv Technol Program, Frederick, MD USA. [Feigelson, Heather Spencer] Kaiser Permanente, Inst Hlth Res, Denver, CO USA. RP Kaaks, R (reprint author), German Canc Res Ctr, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany. EM r.kaaks@dkfz.de; heather.s.feigelson@kp.org RI Cox, David/A-2023-2009; Pollak, Michael/G-9094-2011; Dossus, Laure/B-2875-2013; Clavel-Chapelon, Francoise/G-6733-2014; Panico, Salvatore/K-6506-2016 OI Cox, David/0000-0002-2152-9259; Pollak, Michael/0000-0003-3047-0604; Dossus, Laure/0000-0003-2716-5748; Panico, Salvatore/0000-0002-5498-8312 FU US National Institutes of Health, National Cancer Institute [U01-CA98233, U01-CA98710, U01-CA98216, U01-CA98758]; NIH/National Cancer Institute, Division of Cancer Epidemiology and Genetics FX This work was supported by the US National Institutes of Health, National Cancer Institute (cooperative agreements U01-CA98233 to D.J.H., U01-CA98710 to M.J. T., U01-CA98216 to E.R. and R.K., and U01-CA98758 to B. E. H., and Intramural Research Program of NIH/National Cancer Institute, Division of Cancer Epidemiology and Genetics). NR 84 TC 29 Z9 29 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 EI 1460-2083 J9 HUM MOL GENET JI Hum. Mol. Genet. PD OCT PY 2010 VL 19 IS 19 BP 3873 EP 3884 DI 10.1093/hmg/ddq291 PG 12 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 648UD UT WOS:000281718900016 PM 20634197 ER PT J AU Eijgelsheim, M Newton-Cheh, C Sotoodehnia, N de Bakker, PIW Muller, M Morrison, AC Smith, AV Isaacs, A Sanna, S Dorr, M Navarro, P Fuchsberger, C Nolte, IM de Geus, EJC Estrada, K Hwang, SJ Bis, JC Ruckert, IM Alonso, A Launer, LJ Hottenga, JJ Rivadeneira, F Noseworthy, PA Rice, KM Perz, S Arking, DE Spector, TD Kors, JA Aulchenko, YS Tarasov, KV Homuth, G Wild, SH Marroni, F Gieger, C Licht, CM Prineas, RJ Hofman, A Rotter, JI Hicks, AA Ernst, F Najjar, SS Wright, AF Peters, A Fox, ER Oostra, BA Kroemer, HK Couper, D Volzke, H Campbell, H Meitinger, T Uda, M Witteman, JCM Psaty, BM Wichmann, HE Harris, TB Kaab, S Siscovick, DS Jamshidi, Y Uitterlinden, AG Folsom, AR Larson, MG Wilson, JF Penninx, BW Snieder, H Pramstaller, PP van Duijn, CM Lakatta, EG Felix, SB Gudnason, V Pfeufer, A Heckbert, SR Stricker, BHC Boerwinkle, E O'Donnell, CJ AF Eijgelsheim, Mark Newton-Cheh, Christopher Sotoodehnia, Nona de Bakker, Paul I. W. Mueller, Martina Morrison, Alanna C. Smith, Albert V. Isaacs, Aaron Sanna, Serena Doerr, Marcus Navarro, Pau Fuchsberger, Christian Nolte, Ilja M. de Geus, Eco J. C. Estrada, Karol Hwang, Shih-Jen Bis, Joshua C. Rueckert, Ina-Maria Alonso, Alvaro Launer, Lenore J. Hottenga, Jouke Jan Rivadeneira, Fernando Noseworthy, Peter A. Rice, Kenneth M. Perz, Siegfried Arking, Dan E. Spector, Tim D. Kors, Jan A. Aulchenko, Yurii S. Tarasov, Kirill V. Homuth, Georg Wild, Sarah H. Marroni, Fabio Gieger, Christian Licht, Carmilla M. Prineas, Ronald J. Hofman, Albert Rotter, Jerome I. Hicks, Andrew A. Ernst, Florian Najjar, Samer S. Wright, Alan F. Peters, Annette Fox, Ervin R. Oostra, Ben A. Kroemer, Heyo K. Couper, David Voelzke, Henry Campbell, Harry Meitinger, Thomas Uda, Manuela Witteman, Jacqueline C. M. Psaty, Bruce M. Wichmann, H-Erich Harris, Tamara B. Kaeaeb, Stefan Siscovick, David S. Jamshidi, Yalda Uitterlinden, Andre G. Folsom, Aaron R. Larson, Martin G. Wilson, James F. Penninx, Brenda W. Snieder, Harold Pramstaller, Peter P. van Duijn, Cornelia M. Lakatta, Edward G. Felix, Stephan B. Gudnason, Vilmundur Pfeufer, Arne Heckbert, Susan R. Stricker, Bruno H. Ch. Boerwinkle, Eric O'Donnell, Christopher J. TI Genome-wide association analysis identifies multiple loci related to resting heart rate SO HUMAN MOLECULAR GENETICS LA English DT Article ID RECTIFIER POTASSIUM CHANNEL; CARDIAC-PACEMAKER CELLS; QT INTERVAL DURATION; MYOSIN HEAVY-CHAIN; MIDDLE-AGED MEN; COMMON VARIANTS; FUNCTIONAL EXPRESSION; ADRENERGIC-RECEPTOR; GENETIC-VARIANTS; RISK-FACTOR AB Higher resting heart rate is associated with increased cardiovascular disease and mortality risk. Though heritable factors play a substantial role in population variation, little is known about specific genetic determinants. This knowledge can impact clinical care by identifying novel factors that influence pathologic heart rate states, modulate heart rate through cardiac structure and function or by improving our understanding of the physiology of heart rate regulation. To identify common genetic variants associated with heart rate, we performed a meta-analysis of 15 genome-wide association studies (GWAS), including 38 991 subjects of European ancestry, estimating the association between age-, sex- and body mass-adjusted RR interval (inverse heart rate) and similar to 2.5 million markers. Results with P < 5 x 10(-8) were considered genome-wide significant. We constructed regression models with multiple markers to assess whether results at less stringent thresholds were likely to be truly associated with RR interval. We identified six novel associations with resting heart rate at six loci: 6q22 near GJA1; 14q12 near MYH7; 12p12 near SOX5, c12orf67, BCAT1, LRMP and CASC1; 6q22 near SLC35F1, PLN and c6orf204; 7q22 near SLC12A9 and UfSp1; and 11q12 near FADS1. Associations at 6q22 400 kb away from GJA1, at 14q12 MYH6 and at 1q32 near CD34 identified in previously published GWAS were confirmed. In aggregate, these variants explain similar to 0.7% of RR interval variance. A multivariant regression model including 20 variants with P < 10(-5) increased the explained variance to 1.6%, suggesting that some loci falling short of genome-wide significance are likely truly associated. Future research is warranted to elucidate underlying mechanisms that may impact clinical care. C1 [Eijgelsheim, Mark; Isaacs, Aaron; Rivadeneira, Fernando; Aulchenko, Yurii S.; Hofman, Albert; Witteman, Jacqueline C. M.; Uitterlinden, Andre G.; van Duijn, Cornelia M.; Stricker, Bruno H. Ch.] Erasmus MC, Dept Epidemiol, NL-3000 CA Rotterdam, Netherlands. [Estrada, Karol; Rivadeneira, Fernando; Uitterlinden, Andre G.; Stricker, Bruno H. Ch.] Erasmus MC, Dept Internal Med, NL-3000 CA Rotterdam, Netherlands. [Kors, Jan A.; Stricker, Bruno H. Ch.] Erasmus MC, Dept Med Informat, NL-3000 CA Rotterdam, Netherlands. [Oostra, Ben A.] Erasmus MC, Dept Clin Genet, NL-3000 CA Rotterdam, Netherlands. [Newton-Cheh, Christopher; Noseworthy, Peter A.] Massachusetts Gen Hosp, Ctr Human Genet Res, Cardiovasc Res Ctr, Boston, MA 02114 USA. [O'Donnell, Christopher J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Newton-Cheh, Christopher; de Bakker, Paul I. W.] Broad Inst Harvard & MIT, Program Med Populat Genet, Cambridge, MA USA. [Newton-Cheh, Christopher; Hwang, Shih-Jen; Larson, Martin G.; O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Sotoodehnia, Nona] Univ Washington, Sch Med, Dept Med, Div Cardiol, Seattle, WA 98195 USA. [Sotoodehnia, Nona; Bis, Joshua C.; Psaty, Bruce M.; Siscovick, David S.; Heckbert, Susan R.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. [Psaty, Bruce M.; Siscovick, David S.; Heckbert, Susan R.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. [de Bakker, Paul I. W.] Brighams & Womens Hosp, Div Genet, Dept Med, Boston, MA USA. [Mueller, Martina; Wichmann, H-Erich; Kaeaeb, Stefan] German Res Ctr Environm Hlth, Helmholtz Ctr Munich, Inst Epidemiol, Neuherberg, Germany. [Mueller, Martina; Rueckert, Ina-Maria; Gieger, Christian; Peters, Annette; Wichmann, H-Erich] Univ Munich, Inst Med Informat Biometry & Epidemiol, Chair Epidemiol, Univ Hosp Grosshadern, Munich, Germany. [Mueller, Martina] Univ Munich, Dept Med 1, Univ Hosp Grosshadern, Munich, Germany. [Morrison, Alanna C.; Boerwinkle, Eric] Univ Texas Hlth Sci Ctr, Ctr Human Genet, Houston, TX USA. [Smith, Albert V.; Gudnason, Vilmundur] Iceland Heart Assoc Res Inst, Kopavogur, Iceland. [Sanna, Serena; Uda, Manuela] Cittadella Univ Monserrato, Ist Neurogenet & Neurofarmacol, Consiglio Nazl Ric, Cagliari, Italy. [Doerr, Marcus; Felix, Stephan B.] Ernst Moritz Arndt Univ Greifswald, Dept Internal Med B, Greifswald, Germany. [Homuth, Georg; Ernst, Florian] Ernst Moritz Arndt Univ Greifswald, Interfac Inst Genet & Funct Genom, Greifswald, Germany. [Voelzke, Henry] Ernst Moritz Arndt Univ Greifswald, Inst Community Med, Greifswald, Germany. [Navarro, Pau; Wright, Alan F.] Western Gen Hosp, MRC Human Genet Unit, Inst Genet & Mol Med, Edinburgh EH4 2XU, Midlothian, Scotland. [Fuchsberger, Christian; Marroni, Fabio; Hicks, Andrew A.; Pramstaller, Peter P.] European Acad Bozen Bolzano EURAC, Inst Med Genet, Bolzano, Italy. [Nolte, Ilja M.; Snieder, Harold] Univ Groningen, Univ Med Ctr Groningen, Unit Genet Epidemiol & Bioinformat, Dept Epidemiol, NL-9713 AV Groningen, Netherlands. [de Geus, Eco J. C.; Hottenga, Jouke Jan] Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands. [Alonso, Alvaro; Folsom, Aaron R.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA. [Launer, Lenore J.; Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Perz, Siegfried] Helmholtz Zentrum Munchen, Inst Biol & Med Imaging, Munich, Germany. [Arking, Dan E.] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD USA. [Arking, Dan E.] Johns Hopkins Univ, Sch Med, Dept Med, Div Cardiol, Baltimore, MD 21205 USA. [Spector, Tim D.; Jamshidi, Yalda; Snieder, Harold] St Thomas Hosp, Dept Twin Res, Kings Coll London, London, England. [Spector, Tim D.; Jamshidi, Yalda; Snieder, Harold] St Thomas Hosp, Genet Epidemiol Unit, Kings Coll London, London, England. [Tarasov, Kirill V.; Najjar, Samer S.; Lakatta, Edward G.] NIA, Cardiovasc Sci Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. [Wild, Sarah H.; Campbell, Harry; Wilson, James F.] Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland. [Marroni, Fabio] Inst Appl Genom, Udine, Italy. [Licht, Carmilla M.; Penninx, Brenda W.] Vrije Univ Amsterdam Med Ctr, Dept Psychiat, Amsterdam, Netherlands. [Prineas, Ronald J.] EPICARE Ctr, Salem, NC USA. [Hofman, Albert; Witteman, Jacqueline C. M.; Uitterlinden, Andre G.; van Duijn, Cornelia M.; Stricker, Bruno H. Ch.] Netherlands Genom Initiat Sponsored Netherlands C, Rotterdam, Netherlands. [Rotter, Jerome I.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA. [Fox, Ervin R.] Univ Mississippi, Med Ctr, Div Cardiol, Jackson, MS 39216 USA. [Kroemer, Heyo K.] Ctr Pharmacol & Expt Therapeut, Dept Pharmacol, Greifswald, Germany. [Couper, David] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA. [Meitinger, Thomas; Pfeufer, Arne] Helmholtz Ctr Munich, Inst Human Genet, Munich, Germany. [Meitinger, Thomas; Pfeufer, Arne] Tech Univ Munich, Klinikum Rechts Isar, Inst Human Genet, D-8000 Munich, Germany. [Psaty, Bruce M.; Heckbert, Susan R.] Grp Hlth Res Inst, Seattle, WA USA. [Wichmann, H-Erich] Univ Munich, Klinikum Grosshadern, D-8000 Munich, Germany. [Jamshidi, Yalda] St Georges Univ London, London, England. [Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. [Pramstaller, Peter P.] Gen Cent Hosp, Dept Neurol, Bolzano, Italy. [Pramstaller, Peter P.] Med Univ Lubeck, Dept Neurol, D-23538 Lubeck, Germany. [Gudnason, Vilmundur] Univ Iceland, Reykjavik, Iceland. [Stricker, Bruno H. Ch.] Inspectorate Hlth Care, The Hague, Netherlands. [O'Donnell, Christopher J.] NHLBI, Bethesda, MD 20892 USA. RP Stricker, BHC (reprint author), Erasmus MC, Dept Epidemiol, POB 2040, NL-3000 CA Rotterdam, Netherlands. EM b.stricker@erasmusmc.nl; odonnellc@nhlbi.nih.gov RI Meitinger, Thomas/O-1318-2015; Rivadeneira, Fernando/O-5385-2015; Smith, Albert/K-5150-2015; Hicks, Andrew/E-9518-2017; Alonso, Alvaro/A-4917-2010; Aulchenko, Yurii/M-8270-2013; de Bakker, Paul/B-8730-2009; Pramstaller, Peter/C-2357-2008; Peters, Annette/A-6117-2011; Gudnason, Vilmundur/K-6885-2015; Wilson, James F/A-5704-2009; de Geus, Eco/M-9318-2015; Fuchsberger, Christian/C-9646-2010; Max, Mad/E-5238-2010; Kaab, Stefan/H-3915-2012; Rice, Kenneth/A-4150-2013; Pfeufer, Arne/B-6634-2013; OI Rivadeneira, Fernando/0000-0001-9435-9441; Smith, Albert/0000-0003-1942-5845; Hicks, Andrew/0000-0001-6320-0411; Larson, Martin/0000-0002-9631-1254; Marroni, Fabio/0000-0002-1556-5907; Fuchsberger, Christian/0000-0002-5918-8947; sanna, serena/0000-0002-3768-1749; Jamshidi, Yalda/0000-0003-0151-6482; Alonso, Alvaro/0000-0002-2225-8323; Aulchenko, Yurii/0000-0002-7899-1575; de Bakker, Paul/0000-0001-7735-7858; Gudnason, Vilmundur/0000-0001-5696-0084; Wilson, James F/0000-0001-5751-9178; de Geus, Eco/0000-0001-6022-2666; Max, Mad/0000-0001-6966-6829; Rice, Kenneth/0000-0001-5779-4495; Gieger, Christian/0000-0001-6986-9554 FU Chief Scientist Office [CZB/4/710]; Medical Research Council [MC_U127561128, MC_U127592696]; None [NIH2000501635]; PHS HHS [2000501635] NR 65 TC 62 Z9 63 U1 0 U2 8 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 OCT PY 2010 VL 19 IS 19 BP 3885 EP 3894 DI 10.1093/hmg/ddq303 PG 10 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 648UD UT WOS:000281718900017 PM 20639392 ER PT J AU Johnston, JJ Sapp, JC Turner, JT Amor, D Aftimos, S Aleck, KA Bocian, M Bodurtha, JN Cox, GF Curry, CJ Day, R Donnai, D Field, M Fujiwara, I Gabbett, M Gal, M Graham, JM Hedera, P Hennekam, RCM Hersh, JH Hopkin, RJ Kayserili, H Kidd, AMJ Kimonis, V Lin, AE Lynch, SA Maisenbacher, M Mansour, S McGaughran, J Mehta, L Murphy, H Raygada, M Robin, NH Rope, AF Rosenbaum, KN Schaefer, GB Shealy, A Smith, W Soller, M Sommer, A Stalker, HJ Steiner, B Stephan, MJ Tilstra, D Tomkins, S Trapane, P Tsai, ACH Van Allen, MI Vasudevan, PC Zabel, B Zunich, J Black, GCM Biesecker, LG AF Johnston, Jennifer J. Sapp, Julie C. Turner, Joyce T. Amor, David Aftimos, Salim Aleck, Kyrieckos A. Bocian, Maureen Bodurtha, Joann N. Cox, Gerald F. Curry, Cynthia J. Day, Ruth Donnai, Dian Field, Michael Fujiwara, Ikuma Gabbett, Michael Gal, Moran Graham, John M., Jr. Hedera, Peter Hennekam, Raoul C. M. Hersh, Joseph H. Hopkin, Robert J. Kayserili, Hulya Kidd, Alexa M. J. Kimonis, Virginia Lin, Angela E. Lynch, Sally Ann Maisenbacher, Melissa Mansour, Sahar McGaughran, Julie Mehta, Lakshmi Murphy, Helen Raygada, Margarita Robin, Nathaniel H. Rope, Alan F. Rosenbaum, Kenneth N. Schaefer, G. Bradley Shealy, Amy Smith, Wendy Soller, Maria Sommer, Annmarie Stalker, Heather J. Steiner, Bernhard Stephan, Mark J. Tilstra, David Tomkins, Susan Trapane, Pamela Tsai, Anne Chun-Hui Van Allen, Margot I. Vasudevan, Pradeep C. Zabel, Bernhard Zunich, Janice Black, Graeme C. M. Biesecker, Leslie G. TI Molecular Analysis Expands the Spectrum of Phenotypes Associated with GLI3 Mutations SO HUMAN MUTATION LA English DT Article DE GLI3; Greig syndrome; Pallister-Hall syndrome; oral-facial-digital syndrome ID PALLISTER-HALL-SYNDROME; FACIAL-DIGITAL SYNDROME; GREIG CEPHALOPOLYSYNDACTYLY SYNDROME; MORPHOLOGY STANDARD TERMINOLOGY; POLYDACTYLY TYPE-IV; SYNDROME TYPE-VI; HYPOTHALAMIC HAMARTOMA; ACROCALLOSAL SYNDROME; GENE; PATIENT AB A range of phenotypes including Greig cephalopolysyndactyly and Pallister-Hall syndromes (GCPS, PHS) are caused by pathogenic mutation of the GLI3 gene. To characterize the clinical variability of GLI3 mutations, we present a subset of a cohort of 174 probands referred for GLI3 analysis. Eighty-one probands with typical GCPS or PHS were previously reported, and we report the remaining 93 probands here. This includes 19 probands (12 mutations) who fulfilled clinical criteria for GCPS or PHS, 48 probands (16 mutations) with features of GCPS or PHS but who did not meet the clinical criteria (sub-GCPS and sub-PHS), 21 probands (6 mutations) with features of PHS or GCPS and oral-facial- digital syndrome, and 5 probands (1 mutation) with nonsyndromic polydactyly. These data support previously identified genotype-phenotype correlations and demonstrate a more variable degree of severity than previously recognized. The finding of GLI3 mutations in patients with features of oral-facial-digital syndrome supports the observation that GLI3 interacts with cilia. We conclude that the phenotypic spectrum of GLI3 mutations is broader than that encompassed by the clinical diagnostic criteria, but the genotype-phenotype correlation persists. Individuals with features of either GCPS or PHS should be screened for mutations in GLI3 even if they do not fulfill clinical criteria. Hum Mutat 31:1142-1154, 2010. (C) 2010 Wiley-Liss, Inc. C1 [Johnston, Jennifer J.; Sapp, Julie C.; Turner, Joyce T.; Biesecker, Leslie G.] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. [Amor, David] Royal Childrens Hosp, Murdoch Childrens Res Inst, Parkville, Vic 3052, Australia. [Aftimos, Salim] Auckland City Hosp, No Reg Genet Serv, Auckland, New Zealand. [Aleck, Kyrieckos A.] St Josephs Hosp, Phoenix, AZ USA. [Bocian, Maureen; Kimonis, Virginia] Univ Calif Irvine, Dept Pediat, Med Ctr, Div Genet & Metab, Orange, CA 92668 USA. [Bodurtha, Joann N.] Virginia Commonwealth Univ, Dept Human & Mol Genet Pediat Obstet Gynecol Epid, Richmond, VA USA. [Cox, Gerald F.] Harvard Univ, Sch Med, Div Genet, Boston, MA USA. [Cox, Gerald F.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. [Cox, Gerald F.] Genzyme Corp, Clin Res, Cambridge, MA USA. [Curry, Cynthia J.] Genet Med Cent Calif Univ Calif, San Francisco, CA USA. [Day, Ruth] Cheshire & Merseyside Clin Genet Serv, Liverpool, Merseyside, England. [Donnai, Dian; Murphy, Helen; Black, Graeme C. M.] Univ Manchester, Manchester Acad Heath Sci Ctr, Cent Manchester Univ Hosp NHS Fdn Trust, Manchester, Lancs, England. [Field, Michael] Nepean Hosp, Dept Clin Genet, Penrith, NSW, Australia. [Fujiwara, Ikuma] Tohoku Univ Sch Med, Tohoku Univ Hosp, Dept Pediat, Sendai, Miyagi, Japan. [Gabbett, Michael; McGaughran, Julie] Univ Queensland, Sch Med, Brisbane, Qld, Australia. [Gabbett, Michael; McGaughran, Julie] Royal Brisbane & Womens Hosp, Brisbane, Qld, Australia. [Gal, Moran] Shaare Zedek Med Ctr, Inst Med Genet, Jerusalem, Israel. [Graham, John M., Jr.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pediat, Med Genet Inst,Cedars Sinai Med Ctr, Los Angeles, CA 90095 USA. [Hedera, Peter] Vanderbilt Univ, Dept Neurol, Nashville, TN USA. [Hennekam, Raoul C. M.] Univ Amsterdam, Acad Med Ctr, Dept Pediat, Meibergdreef, Az Amsterdam, Netherlands. [Hersh, Joseph H.] Univ Louisville, Sch Med, Dept Pediat, Louisville, KY 40292 USA. [Hopkin, Robert J.] Cincinnati Childrens Hosp Med Ctr, Div Human Genet, Cincinnati, OH USA. [Kayserili, Hulya] Istanbul Univ, Istanbul Fac Med, Dept Med Genet, Istanbul, Turkey. [Kidd, Alexa M. J.] Canterbury Hlth Labs, Christchurch, New Zealand. [Lin, Angela E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Lynch, Sally Ann] Our Ladys Childrens Hosp, Natl Ctr Med Genet, Dublin 12, Ireland. [Maisenbacher, Melissa; Stalker, Heather J.] Univ Florida, Dept Pediat, Div Genet & Metab, Gainesville, FL USA. [Mansour, Sahar] Univ London, SW Thames Reg Genet Serv, London, England. [Mehta, Lakshmi] Mt Sinai Sch Med, Dept Genet & Genom Sci, Div Med Genet, New York, NY USA. [Raygada, Margarita] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Clin & Dev Genom, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA. [Robin, Nathaniel H.] Univ Alabama, Dept Genet & Pediat, Birmingham, AL USA. [Rope, Alan F.] Univ Utah Sch Med, Div Med Genet, Salt Like City, UT USA. [Rosenbaum, Kenneth N.] Childrens Natl Med Ctr, Dept Med Genet, Washington, DC 20010 USA. [Schaefer, G. Bradley] Univ Arkansas Med Sci, Arkansas Childrens Hosp, Dept Genet & Pediat, Sect Genet & Metab,Dept Pediat, Little Rock, AR 72205 USA. [Shealy, Amy] Cleveland Clin, Genom Med Inst, Cleveland, OH 44106 USA. [Smith, Wendy] Barbara Bush Childrens Hosp Maine Med Ctr, Portland, ME USA. [Soller, Maria] Univ Lund Hosp, Div Clin Genet, Univ & Reg Labs Reg Skane, S-22185 Lund, Sweden. [Sommer, Annmarie] Ohio State Univ Coll Med, Dept Pediat, Columbus, OH USA. [Sommer, Annmarie] Nationwide Childrens Hosp, Columbus, OH USA. [Steiner, Bernhard] Univ Zurich, Inst Med Genet, CH-8603 Schwerzenbach, Switzerland. [Stephan, Mark J.] Madigan Army Med Ctr, Dept Pediat, Tacoma, WA 98431 USA. [Tilstra, David] CentraCare Clin, Dept Pediat, St Cloud, MN USA. [Tomkins, Susan] Univ Hosp Bristol, Bristol, Avon, England. [Trapane, Pamela] Univ Iowa Hosp & Clin, Dept Pediat, Iowa City, IA 52242 USA. [Tsai, Anne Chun-Hui] Univ Colorado, Hlth Sci Ctr, Dept Pediat, Denver, CO 80262 USA. [Van Allen, Margot I.] Univ British Columbia, Dept Med Genet, Vancouver, BC, Canada. [Vasudevan, Pradeep C.] Univ Leicester, Univ Hosp Leicester NHS Trust, Leicester, Leics, England. [Zabel, Bernhard] Univ Hosp Freiburg, Dept Pediat, Freiburg, Germany. [Zunich, Janice] Indiana Univ Sch Med NW, Genet Ctr, Gary, IN USA. RP Johnston, JJ (reprint author), NHGRI, Genet Dis Res Branch, NIH, Bldg 49,Room 4C64, Bethesda, MD 20892 USA. EM jjohnsto@mail.nih.gov RI Gabbett, Michael/C-3228-2012; McGaughran, Julie/A-2563-2012; OI Black, Graeme/0000-0001-8727-6592; Hopkin, Robert/0000-0003-0770-5516 FU SHARE's Childhood Disability Center; Steven Spielberg Pediatric Research Center; NIH/NICHD [HD22657]; Medical Genetics NIH/NIGMS [5-T32-GM08243]; National Human Genome Research Institute of the National Institutes of Health FX The authors thank the following genetic professionals for referring patients to our study: William P. Allen, David J. Aughton, Christopher Cunniff, Sally Davies, William B. Dobyns, Linda Genen, Daniel Gruskin, Ketil Heimdal, Gail Herman, Jodi Hoffman, Helen Hughes, LaDonna Immken, Jeffrey Innis, Ian Krantz, David Manchester, Elizabeth McPherson, Thomas Morgan, Maximilian Muenke, Tracy Oh, Melissa Parisi, Betsy Peach, Lynda Pollack, Nazneen Rahman, Miranda Splitt and LuAnn Weik. Grant sponsors: SHARE's Childhood Disability Center, the Steven Spielberg Pediatric Research Center, the NIH/NICHD Program Project Grant; grant number: HD22657; the Medical Genetics NIH/NIGMS Training Program Grant; grant number: 5-T32-GM08243 (all to J. M. G). Grant sponsor: funding from the Intramural Research Program of the National Human Genome Research Institute of the National Institutes of Health. We also acknowledge the Manchester NIHR Biomedical research Centre. Disclaimer: The opinions and assertions contained herein are the views of the authors and are not to be construed as official or as reflecting the views of the United States Department of Defense. NR 35 TC 33 Z9 33 U1 0 U2 9 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PD OCT PY 2010 VL 31 IS 10 BP 1142 EP 1154 DI 10.1002/humu.21328 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA 660OW UT WOS:000282653900008 PM 20672375 ER PT J AU Zhang, HP Legro, RS Zhang, J Zhang, L Chen, XA Huang, H Casson, PR Schlaff, WD Diamond, MP Krawetz, SA Coutifaris, C Brzyski, RG Christman, GM Santoro, N Eisenberg, E AF Zhang, Heping Legro, Richard S. Zhang, Jeffrey Zhang, Leon Chen, Xiang Huang, Hao Casson, Peter R. Schlaff, William D. Diamond, Michael P. Krawetz, Stephen A. Coutifaris, Christos Brzyski, Robert G. Christman, Gregory M. Santoro, Nanette Eisenberg, Esther CA Reprod Med Network TI Decision trees for identifying predictors of treatment effectiveness in clinical trials and its application to ovulation in a study of women with polycystic ovary syndrome SO HUMAN REPRODUCTION LA English DT Article DE PCOS; ovulation induction; decision trees; treatment effectiveness ID NORMOGONADOTROPIC OLIGOAMENORRHEIC INFERTILITY; CLOMIPHENE CITRATE INDUCTION; PREGNANCY COMPLICATIONS; METFORMIN; WEIGHT AB Double-blind, randomized clinical trials are the preferred approach to demonstrating the effectiveness of one treatment against another. The comparison is, however, made on the average group effects. While patients and clinicians have always struggled to understand why patients respond differently to the same treatment, and while much hope has been held for the nascent field of predictive biomarkers (e.g. genetic markers), there is still much utility in exploring whether it is possible to estimate treatment efficacy based on demographic and baseline variables. The pregnancy in polycystic ovary syndrome (PPCOS) study was a prospective, multi-center, randomized clinical trial comparing three ovulation induction regimens: clomiphene citrate (CC), metformin and the combination of the two. There were 446 women who ovulated in response to the treatments among the entire 626 participants. In this report, we focus on the 418 women who received CC (alone or combined with metformin) to determine if readily available baseline physical characteristics and/or easily obtainable baseline measures could be used to distinguish treatment effectiveness in stimulating ovulation. We used a recursive partitioning technique and developed a node-splitting rule to build decision tree models that reflected within-node and within-treatment responses. Overall, the combination of CC plus metformin resulted in an increased incidence of ovulation compared with CC alone. This is particularly so in women with relatively larger left ovarian volumes (>= 19.5 cubic cm), and a left ovarian volume < 19.5 cubic cm was related to treatment outcomes for all subsequent nodes. Women who were older, who had higher baseline insulin, higher waist-to-hip circumference ratio or higher sex hormone-binding globulin levels had better ovulatory rates with CC alone than with the combination of CC plus metformin. Polycystic ovary syndrome (PCOS) is a phenotypically diverse condition. Both baseline laboratory and clinical parameters can predict the ovulatory response in women with PCOS undergoing ovulation induction. Without a priori hypotheses with regard to any predictors, the observation regarding left ovary volume is novel and worthy of further investigation and validation. C1 [Zhang, Heping; Chen, Xiang; Huang, Hao] Yale Univ, Dept Epidemiol & Publ Hlth, Sch Med, New Haven, CT 06520 USA. [Legro, Richard S.] Penn State Univ, Dept Obstet & Gynecol, Hershey, PA USA. [Zhang, Jeffrey; Zhang, Leon] Guilford High Sch, Guilford, CT USA. [Casson, Peter R.] Univ Vermont, Dept Med & Obstet & Gynecol, Burlington, VT USA. [Schlaff, William D.; Santoro, Nanette] Univ Colorado, Dept Obstet & Gynecol, Denver, CO 80202 USA. [Diamond, Michael P.; Krawetz, Stephen A.] Wayne State Univ, Dept Obstet, Detroit, MI USA. [Diamond, Michael P.; Krawetz, Stephen A.] Wayne State Univ, Dept Gynecol, Detroit, MI USA. [Coutifaris, Christos] Univ Penn, Philadelphia, PA 19104 USA. [Brzyski, Robert G.] Univ Texas Hlth Sci Ctr San Antonio, Dept Obstet & Gynecol, San Antonio, TX 78229 USA. [Christman, Gregory M.] Univ Michigan, Dept Obstet & Gynecol, Reprod Sci Program, Ann Arbor, MI 48109 USA. [Eisenberg, Esther] NICHHD, Reprod Sci Branch, Bethesda, MD 20892 USA. RP Zhang, HP (reprint author), Yale Univ, Dept Epidemiol & Publ Hlth, Sch Med, New Haven, CT 06520 USA. EM heping.zhang@yale.edu OI Diamond, Michael/0000-0001-6353-4489 FU NIH/NICHD [U10HD055925, U10 HD038992, U10 HD038998, U10 HD027049, U10 HD039005, U10 HD055936, U10 HD055942, H10 HD055944] FX This work was supported in part by NIH/NICHD grantsU10HD055925 (H.Z.), U10 HD038992 (R. L.), U10 HD038998 (W. S.), U10 HD027049 (C. C.), U10 HD039005 (M. D.), U10 HD055936 (G. C.), U10 HD055942 (R. B.) and H10 HD055944 (P. C.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NICHD or NIH. NR 29 TC 15 Z9 15 U1 0 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 OCT PY 2010 VL 25 IS 10 BP 2612 EP 2621 DI 10.1093/humrep/deq210 PG 10 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 651WX UT WOS:000281959200025 PM 20716558 ER PT J AU Selby, JV Lee, J Swain, BE Tavel, HM Ho, PM Margolis, KL O'Connor, PJ Fine, L Schmittdiel, JA Magid, DJ AF Selby, Joe V. Lee, Janelle Swain, Bix E. Tavel, Heather M. Ho, P. Michael Margolis, Karen L. O'Connor, Patrick J. Fine, Lawrence Schmittdiel, Julie A. Magid, David. J. TI Trends in Time to Confirmation and Recognition of New-Onset Hypertension, 2002-2006 SO HYPERTENSION LA English DT Article DE hypertension; electronic health records; registries; early detection; screening ID AMBULATORY BLOOD-PRESSURE; CARDIOVASCULAR-DISEASE; DIABETES-MELLITUS; RISK; MANAGEMENT; CARE; VARIABILITY; POPULATION; ADULTS; TRIAL AB Achieving full benefits of blood pressure control in populations requires prompt recognition of previously undetected hypertension. In 2003, the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure provided definitions of hypertension and recommended that single elevated readings be confirmed within 1 to 2 months. We sought to determine whether the time required to confirm and recognize (ie, diagnose and/or treat) new-onset hypertension decreased from 2002 to 2006 for adult members of 2 large integrated healthcare delivery systems, Kaiser Permanente Northern California and Colorado. Using electronically stored office blood pressure readings, physician diagnoses, and pharmacy prescriptions, we identified 200 587 patients with new-onset hypertension (2002-2006) marked by 2 consecutive elevated blood pressure readings in previously undiagnosed, untreated members. Mean confirmation intervals (time from the first to second consecutive elevated reading) declined steadily from 103 to 89 days during this period. For persons recognized within 12 months after confirmation, the mean interval to recognition declined from 78 to 61 days. However, only 33% of individuals were recognized within 12 months. One third were never recognized during observed follow-up. For these patients, most subsequent blood pressure recordings were not elevated. Higher initial blood pressure levels, history of previous cardiovascular disease, and older age were associated with shorter times to recognition. Times to confirmation and recognition of new-onset hypertension have become shorter in recent years, especially for patients with higher cardiovascular disease risk. Variability in office-based blood pressure readings suggests that further improvements in recognition and treatment may be achieved with more specific automated approaches to identifying hypertension. (Hypertension. 2010;56:605-611.) C1 [Selby, Joe V.; Lee, Janelle; Swain, Bix E.; Schmittdiel, Julie A.] Kaiser Permanente No Calif, Div Res, Oakland, CA USA. [Tavel, Heather M.; Magid, David. J.] Kaiser Permanente Colorado, Inst Hlth Res, Denver, CO USA. [Ho, P. Michael] Denver Vet Affairs Med Ctr, Denver, CO USA. [Ho, P. Michael] Univ Colorado, Denver, CO 80202 USA. [Margolis, Karen L.; O'Connor, Patrick J.] HealthPartners Res Fdn, Minneapolis, MN USA. [Fine, Lawrence] NHLBI, NIH, Bethesda, MD 20892 USA. RP Selby, JV (reprint author), Kaiser Permanente, Div Res, 2000 Broadway, Oakland, CA 94612 USA. EM joe.selby@kp.org FU National Heart, Lung, and Blood Institute [U19HL091179]; Office of Research in Women's Health Building Interdisciplinary Careers [K12HD052163]; Veterans' Affairs Research and Development [05-026-2] FX This study was supported by the National Heart, Lung, and Blood Institute (award No. U19HL091179). J.A.S. is supported by the Office of Research in Women's Health Building Interdisciplinary Careers in Women's Health K12 Career Development Award (K12HD052163). P.M.H. is supported by a Veterans' Affairs Research and Development Career Development Award (05-026-2). NR 27 TC 21 Z9 21 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD OCT PY 2010 VL 56 IS 4 BP 605 EP 611 DI 10.1161/HYPERTENSIONAHA.110.153528 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 650VL UT WOS:000281881400011 PM 20733092 ER PT J AU Sutin, AR Scuteri, A Lakatta, EG Tarasov, KV Ferrucci, L Costa, PT Schlessinger, D Uda, M Terracciano, A AF Sutin, Angelina R. Scuteri, Angelo Lakatta, Edward G. Tarasov, Kirill V. Ferrucci, Luigi Costa, Paul T., Jr. Schlessinger, David Uda, Manuela Terracciano, Antonio TI Trait Antagonism and the Progression of Arterial Thickening Women With Antagonistic Traits Have Similar Carotid Arterial Thickness as Men SO HYPERTENSION LA English DT Article DE intima-media thickness; antagonism; anger; atherosclerosis; personality ID CORONARY-HEART-DISEASE; INTIMA-MEDIA THICKNESS; ATHEROSCLEROSIS RISK; METABOLIC SYNDROME; CARDIOVASCULAR REACTIVITY; ANGIOGRAPHIC FINDINGS; PERSONALITY-TRAITS; SOCIAL SUPPORT; ANGER-IN; HOSTILITY AB A large body of evidence links antagonism-related traits with cardiovascular outcomes, but less is known about how psychological traits are associated with intermediate markers of cardiovascular disease. Using a large, community-based sample from Sardinia, Italy (n = 5614), this study examined how trait antagonism (low agreeableness) and its facets are associated with carotid artery intima-media thickness, a measure of arterial thickening. Controlling for demographic and cardiovascular risk factors, low agreeableness and, in particular, low straightforwardness and low compliance, were associated with greater carotid thickening, measured concurrently and prospectively, and with increases in intima-media thickness over 3 years. Indeed, those in the bottom 10% of agreeableness had a 40% increase in risk for elevated intima-media thickness. Although men have thicker arterial walls, women with antagonistic traits had similar carotid thickening as antagonistic men. Antagonistic individuals, especially those who are manipulative and aggressive, have greater increases in arterial thickening, independent of traditional cardiovascular risk factors. (Hypertension. 2010;56:617-622.) C1 [Sutin, Angelina R.] NIA, Lab Personal & Cognit, NIH, DHHS, Baltimore, MD 21224 USA. [Scuteri, Angelo] Ist Nazl Ricovero & Cura Anziani, UOC Geriatria, Rome, Italy. [Uda, Manuela] CNR, Ist Neurogenet & Neurofarmacol, Cagliari, Italy. RP Sutin, AR (reprint author), NIA, Lab Personal & Cognit, NIH, DHHS, 251 Bayview Blvd, Baltimore, MD 21224 USA. EM sutina@mail.nih.gov RI terracciano, antonio/B-1884-2008; OI Costa, Paul/0000-0003-4375-1712 FU NIH, National Institute on Aging FX This research was supported entirely by the Intramural Research Program of the NIH, National Institute on Aging. NR 37 TC 16 Z9 16 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD OCT PY 2010 VL 56 IS 4 BP 617 EP 622 DI 10.1161/HYPERTENSIONAHA.110.155317 PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 650VL UT WOS:000281881400013 PM 20713913 ER PT J AU Jennings, BL Sahan-Firat, S Estes, AM Das, K Farjana, N Fang, XR Gonzalez, FJ Malik, KU AF Jennings, Brett L. Sahan-Firat, Seyhan Estes, Anne M. Das, Kanak Farjana, Nasreen Fang, Xiao R. Gonzalez, Frank J. Malik, Kafait U. TI Cytochrome P450 1B1 Contributes to Angiotensin II-Induced Hypertension and Associated Pathophysiology SO HYPERTENSION LA English DT Article DE angiotensin II; cytochrome P450 1B1; Cyp1b1(-/-) mice; blood pressure; cardiac and vascular hypertrophy; vascular reactivity; endothelial function ID SMOOTH-MUSCLE-CELLS; CENTRAL-NERVOUS-SYSTEM; ARACHIDONIC-ACID; BLOOD-PRESSURE; 20-HYDROXYEICOSATETRAENOIC ACID; CARDIOVASCULAR-DISEASES; DEPENDENT HYPERTENSION; SUPEROXIDE-PRODUCTION; OXIDATIVE STRESS; NADPH OXIDASE AB Hypertension is the leading cause of cardiovascular diseases, and angiotensin II is one of the major components of the mechanisms that contribute to the development of hypertension. However, the precise mechanisms for the development of hypertension are unknown. Our recent study showing that angiotensin II-induced vascular smooth muscle cell growth depends on cytochrome P450 1B1 led us to investigate its contribution to hypertension caused by this peptide. Angiotensin II was infused via miniosmotic pump into rats (150 ng/kg per minute) or mice (1000 mu g/kg per day) for 13 days resulting in increased blood pressure, increased cardiac and vascular hypertrophy, increased vascular reactivity to vasoconstrictor agents, increased vascular reactive oxygen species production, and endothelial dysfunction in both species. The increase in blood pressure and associated pathophysiological changes were minimized by the cytochrome P450 1B1 inhibitor 2,3',4,5'-tetramethoxystilbene in both species and was markedly reduced in Cyp1b1(-/-) mice. These data suggest that cytochrome P450 1B1 contributes to angiotensin II-induced hypertension and associated pathophysiological changes. Moreover, 2,3',4,5'-tetramethoxystilbene, which prevents both cytochrome P450 1B1-dependent and -independent components of angiotensin II-induced hypertension and inhibits associated pathophysiological changes could be clinically useful in the treatment of hypertension and associated cardiovascular and inflammatory diseases. (Hypertension. 2010;56:667-674.) C1 [Jennings, Brett L.; Sahan-Firat, Seyhan; Estes, Anne M.; Das, Kanak; Farjana, Nasreen; Fang, Xiao R.; Malik, Kafait U.] Univ Tennessee, Ctr Hlth Sci, Dept Pharmacol, Coll Med, Memphis, TN 38163 USA. [Gonzalez, Frank J.] NCI, Lab Metab, Bethesda, MD 20892 USA. RP Malik, KU (reprint author), Univ Tennessee, Ctr Hlth Sci, Dept Pharmacol, Coll Med, 874 Union Ave, Memphis, TN 38163 USA. EM kmalik@uthsc.edu FU National Institutes of Health, National Heart, Lung, and Blood Institute [R01-19134-34]; Neuroscience Institute, University of Tennessee Health Science Center; Scientific and Technical Research Council of Turkey FX The described project was supported by grant R01-19134-34 (to K.U.M.) from the National Institutes of Health, National Heart, Lung, and Blood Institute. B.L.J. was supported in part by a fellowship from the Neuroscience Institute, University of Tennessee Health Science Center. S.S.-F. was supported by the Scientific and Technical Research Council of Turkey. NR 49 TC 31 Z9 32 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD OCT PY 2010 VL 56 IS 4 BP 667 EP U204 DI 10.1161/HYPERTENSIONAHA.110.154518 PG 33 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 650VL UT WOS:000281881400020 PM 20805442 ER PT J AU Vaquero, JJ Udias, JM Seidel, J Espana, S Desco, M AF Vaquero, Juan J. Udias, Jose M. Seidel, Jurgen Espana, Samuel Desco, Manuel TI Effects of the Super Bialkali Photocathode on the Performance Characteristics of a Position-Sensitive Depth-of-Interaction PET Detector Module SO IEEE TRANSACTIONS ON NUCLEAR SCIENCE LA English DT Article DE Gamma-ray detector; PET; photomultiplier ID SCANNER AB Super Bialkali (SBA) photocathode is a new technology that improves the spectral response characteristics of position sensitive PMTs, boosting their quantum efficiency up to 35%. In this experiment, two SBA tubes were introduced into a production line of PET detectors mixed with the regular tubes. The detectors were assembled using the standard factory protocols for detector mounting, calibration and testing. We report an evaluation of the improvement introduced by the SBA photocathode comparing the spatial and energy resolution and the depth-of-interaction (DOI) performance of PET detector modules with DOI capabilities. We conclude that the superior performance of the SBA tube may enable the use of arrays with a larger number of crystals of smaller footprint, thus potentially improving the detector intrinsic spatial resolution without degrading the energy resolution or the phoswich (DOI) discrimination capability. C1 [Vaquero, Juan J.] Hosp Gen Gregorio Maranon, Unidad Med & Cirugia Expt, E-28007 Madrid, Spain. [Udias, Jose M.] Univ Complutense, Dept Fis Atom, Grp Fis Nucl Mol & Nucl, E-28040 Madrid, Spain. [Seidel, Jurgen] NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA. [Seidel, Jurgen] SAIC Frederick Inc, Frederick, MD 21702 USA. [Desco, Manuel] Hosp Gen Gregorio Maranon, Unidad Med & Cirugia Expt, E-28007 Madrid, Spain. [Desco, Manuel] Univ Carlos III Madrid, Dept Bioingn, E-28911 Madrid, Spain. RP Vaquero, JJ (reprint author), Hosp Gen Gregorio Maranon, Unidad Med & Cirugia Expt, E-28007 Madrid, Spain. EM juanjo@mce.hggm.es; jose@nuc2.fis.ucm.es; johnnybgoode@mac.com; samuel@nuc1.fis.ucm.es; desco@mce.hggm.es RI Udias, Jose/A-7523-2010; Vaquero, Juan Jose/D-3033-2009; Desco, Manuel/D-2822-2009; Espana, Samuel/E-9240-2010 OI Udias, Jose/0000-0003-3714-764X; Vaquero, Juan Jose/0000-0001-9200-361X; Desco, Manuel/0000-0003-0989-3231; Espana, Samuel/0000-0001-9092-4597 FU CENIT Program (Ministerio de Industria); Comunidad de Madrid program [ARTEMIS-P2009/DPI-1802, TEC2007-64731/TCM]; RETIC-RECAVA, ISCIII; National Cancer Institute, National Institutes of Health [HHSN261200800001E] FX Manuscript received October 13, 2009; revised January 26, 2010; accepted May 26, 2010. Date of publication July 19, 2010; date of current version October 15, 2010. This work was supported in part by the CENIT Program (Ministerio de Industria), Comunidad de Madrid program ARTEMIS-P2009/DPI-1802, TEC2007-64731/TCM (Ministerio de Educacion y Ciencia), and the RETIC-RECAVA, ISCIII. The contribution of J. Seidel wa supported in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract HHSN261200800001E. The content of this work does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. NR 14 TC 2 Z9 2 U1 2 U2 4 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0018-9499 J9 IEEE T NUCL SCI JI IEEE Trans. Nucl. Sci. PD OCT PY 2010 VL 57 IS 5 BP 2437 EP 2441 DI 10.1109/TNS.2010.2052367 PN 1 PG 5 WC Engineering, Electrical & Electronic; Nuclear Science & Technology SC Engineering; Nuclear Science & Technology GA 670QE UT WOS:000283441600004 ER PT J AU Vendetti, S Davidson, TS Veglia, F Riccomi, A Negri, DRM Lindstedt, R Pasquali, P Shevach, EM De Magistris, MT AF Vendetti, Silvia Davidson, Todd S. Veglia, Filippo Riccomi, Antonella Negri, Donatella R. M. Lindstedt, Ragnar Pasquali, Paolo Shevach, Ethan M. De Magistris, Maria Teresa TI Polyclonal Treg cells enhance the activity of a mucosal adjuvant SO IMMUNOLOGY AND CELL BIOLOGY LA English DT Article DE adjuvant; antigen-specific T-regulatory cells (Treg); cholera toxin; polyclonal Treg ID REGULATORY T-CELLS; CUTTING EDGE; AUTOIMMUNE-DISEASE; FUNCTIONAL INACTIVATION; PROTECTIVE IMMUNITY; INFECTED MICE; CD4(+)CD25(+); RESPONSES; DEPLETION; LUPUS AB The efficacy of vaccines can be greatly improved by adjuvants that enhance and modify the magnitude and the duration of the immune response. Several approaches to design rational adjuvants are based on the suppression of regulatory T-cell (Treg) function. Here, we evaluated whether removal or addition of Treg at the time of vaccination with tetanus toxoid and the mucosal adjuvant cholera toxin (CT), would affect immune responses. We found that depletion/inactivation of CD4(+)CD25(+) Treg, either by treatment of BALB/c mice with anti-CD25 monoclonal antibodies or by adoptive transfer of CD4(+)CD25(-) T lymphocytes depleted of CD4(+)CD25(+) Treg into nu/nu mice, impaired antibody production after mucosal immunization in the presence of CT. Conversely, transfer of polyclonal, but not Ag-specific, CD4(+)CD25(+)Foxp3(+) Treg to normal BALB/c mice enhanced CT-induced antibody responses. An increased titer of both immunoglobulin IgG1 and IgG2a antibody subclasses was found, however, the ratio between IgG1/IgG2a with or without polyclonal Treg was comparable, suggesting that polyclonal Treg influence the magnitude, but not the quality of the immune response. Recipients of polyclonal Treg that had been immunized with CT had an increased number of Ag-specific CD4(+) T cells with an activated phenotype (CD44(hi)) in the draining lymph nodes. This accumulation of Ag-specific CD4(+) T lymphocytes could favour the germinal centre formation and may promote T-dependent B-cell responses. Overall, our study indicates that Foxp3(+) Treg can not only function as suppressor cells but also as helper T cells, depending on the type of immune response being evaluated and the microenvironment in which the response is generated. C1 [Vendetti, Silvia; Veglia, Filippo; Riccomi, Antonella; Negri, Donatella R. M.; De Magistris, Maria Teresa] Ist Super Sanita, Dept Infect Parasit & Immune Mediated Dis, I-00161 Rome, Italy. [Davidson, Todd S.; Shevach, Ethan M.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Lindstedt, Ragnar] Sigma Tau SpA Res & Dev, Dept Immunol, Pomezia, Italy. [Pasquali, Paolo] Ist Super Sanita, Dept Vet Publ Hlth & Food Safety, I-00161 Rome, Italy. RP Vendetti, S (reprint author), Ist Super Sanita, Dept Infect Parasit & Immune Mediated Dis, Viale Regina Elena 299, I-00161 Rome, Italy. EM vendetti@iss.it RI VENDETTI, SILVIA/M-4369-2015; Negri, Donatella/M-4362-2015 OI VENDETTI, SILVIA/0000-0002-8443-496X; Negri, Donatella/0000-0002-3437-9288 FU ISS/NIH [530/0F24]; NIAID, NIH FX We thank Dr JG Chai and Dr G Lombardi for helpful discussions. This work was supported by Grant from the collaboration program ISS/NIH, no. 530/0F24 and by funds from the Intramural Program of the NIAID, NIH. NR 39 TC 15 Z9 15 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0818-9641 J9 IMMUNOL CELL BIOL JI Immunol. Cell Biol. PD OCT PY 2010 VL 88 IS 7 BP 698 EP 706 DI 10.1038/icb.2010.76 PG 9 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 665DA UT WOS:000283014200005 PM 20585335 ER PT J AU Barallon, R Bauer, SR Butler, J Capes-Davis, A Dirks, WG Elmore, E Furtado, M Kline, MC Kohara, A Los, GV MacLeod, RAF Masters, JRW Nardone, M Nardone, RM Nims, RW Price, PJ Reid, YA Shewale, J Sykes, G Steuer, AF Storts, DR Thomson, J Taraporewala, Z Alston-Roberts, C Kerrigan, L AF Barallon, Rita Bauer, Steven R. Butler, John Capes-Davis, Amanda Dirks, Wilhelm G. Elmore, Eugene Furtado, Manohar Kline, Margaret C. Kohara, Arihiro Los, Georgyi V. MacLeod, Roderick A. F. Masters, John R. W. Nardone, Mark Nardone, Roland M. Nims, Raymond W. Price, Paul J. Reid, Yvonne A. Shewale, Jaiprakash Sykes, Gregory Steuer, Anton F. Storts, Douglas R. Thomson, Jim Taraporewala, Zenobia Alston-Roberts, Christine Kerrigan, Liz TI Recommendation of short tandem repeat profiling for authenticating human cell lines, stem cells, and tissues SO IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL LA English DT Review DE Cell authentication; STR profiling; Consensus standard; Quality control ID CONTAMINATION AB Cell misidentification and cross-contamination have plagued biomedical research for as long as cells have been employed as research tools. Examples of misidentified cell lines continue to surface to this day. Efforts to eradicate the problem by raising awareness of the issue and by asking scientists voluntarily to take appropriate actions have not been successful. Unambiguous cell authentication is an essential step in the scientific process and should be an inherent consideration during peer review of papers submitted for publication or during review of grants submitted for funding. In order to facilitate proper identity testing, accurate, reliable, inexpensive, and standardized methods for authentication of cells and cell lines must be made available. To this end, an international team of scientists is, at this time, preparing a consensus standard on the authentication of human cells using short tandem repeat (STR) profiling. This standard, which will be submitted for review and approval as an American National Standard by the American National Standards Institute, will provide investigators guidance on the use of STR profiling for authenticating human cell lines. Such guidance will include methodological detail on the preparation of the DNA sample, the appropriate numbers and types of loci to be evaluated, and the interpretation and quality control of the results. Associated with the standard itself will be the establishment and maintenance of a public STR profile database under the auspices of the National Center for Biotechnology Information. The consensus standard is anticipated to be adopted by granting agencies and scientific journals as appropriate methodology for authenticating human cell lines, stem cells, and tissues. C1 [Elmore, Eugene] Univ Calif Irvine, Dept Radiat Oncol, Irvine, CA 92697 USA. [Barallon, Rita; Thomson, Jim] LGC, Teddington TW11 0LY, Middx, England. [Bauer, Steven R.] FDA Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Off Cellular Tissue & Gene Therapies, Bethesda, MD 20892 USA. [Butler, John; Kline, Margaret C.] NIST, Biochem Sci Div 831, Adv Chem Sci Lab 227, Gaithersburg, MD 20899 USA. [Capes-Davis, Amanda] Childrens Med Res Inst, CellBank Australia, Westmead, NSW, Australia. [Dirks, Wilhelm G.; MacLeod, Roderick A. F.] DSMZ German Collect Microorganisms & Cell Culture, D-38124 Braunschweig, Germany. [Furtado, Manohar; Shewale, Jaiprakash] Appl Markets Genet Syst Life Technol, Foster City, CA 94404 USA. [Kohara, Arihiro] Natl Inst Biomed Innovat, Dept Biomed Resources, Lab Cell Cultures, Osaka 5670085, Japan. [Los, Georgyi V.] Univ Wisconsin, Neurosci Training Program, Madison, WI 53706 USA. [Masters, John R. W.] UCL, Inst Urol, London W1W 7EJ, England. [Nardone, Mark] NIH, Biotrac Program, Fdn Adv Educ Sci, Bethesda, MD 20892 USA. [Nardone, Roland M.] Catholic Univ Amer, Washington, DC 20064 USA. [Nims, Raymond W.] RMC Pharmaceut Solut Inc, Longmont, CO 80501 USA. [Price, Paul J.] D Finit Cell Technol, Charleston, SC 29407 USA. [Steuer, Anton F.] BioReliance, Rockville, MD 20850 USA. [Storts, Douglas R.] Promega Corp, Nucle Acid Technol, Madison, WI 53711 USA. [Taraporewala, Zenobia] FDA Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Off Cellular Tissue & Gene Therapies, Rockville, MD 20852 USA. [Reid, Yvonne A.; Sykes, Gregory; Alston-Roberts, Christine; Kerrigan, Liz] Amer Type Culture Collect, Manassas, VA 20110 USA. RP Elmore, E (reprint author), Univ Calif Irvine, Dept Radiat Oncol, B146D, Irvine, CA 92697 USA. EM eelmore@uci.edu RI Butler, John/C-7812-2011; Bauer, Steven/G-5559-2012; OI Bauer, Steven/0000-0003-2831-846X; Capes-Davis, Amanda/0000-0003-4184-6339 NR 15 TC 38 Z9 39 U1 2 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1071-2690 J9 IN VITRO CELL DEV-AN JI In Vitro Cell. Dev. Biol.-Anim. PD OCT PY 2010 VL 46 IS 9 BP 727 EP 732 DI 10.1007/s11626-010-9333-z PG 6 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 672OC UT WOS:000283594200001 PM 20614197 ER PT J AU Spring, MD Chelimo, K Tisch, DJ Sumba, PO Rochford, R Long, CA Kazura, JW Moormann, AM AF Spring, Michele D. Chelimo, Kiprotich Tisch, Daniel J. Sumba, Peter Odada Rochford, Rosemary Long, Carole A. Kazura, James W. Moormann, Ann M. TI Allele Specificity of Gamma Interferon Responses to the Carboxyl-Terminal Region of Plasmodium falciparum Merozoite Surface Protein 1 by Kenyan Adults with Naturally Acquired Immunity to Malaria SO INFECTION AND IMMUNITY LA English DT Article ID T-CELL RESPONSES; BLOOD-STAGE VACCINE; WESTERN KENYA; INTERLEUKIN-10 RESPONSES; ADHESIVE PROTEIN; PROTECTIVE ROLE; ANTIGEN 1; FRAGMENT; ANTIBODIES; IDENTIFICATION AB Cross-sectional seroepidemiological studies of populations naturally exposed to Plasmodium falciparum suggest an association between protection from malaria and circulating antibodies to the carboxyl terminus of merozoite surface protein 1 (MSP1). Questions remain regarding the significance of cell-mediated immunity to MSP1 in conferring protection and inducing immunologic memory. Vaccine constructs have been based on the 42-kDa recombinant MSP1 protein (MSP1(42)), which includes the 19-kDa (MSP1(19)) and 33-kDa (MSP1(33)) fragments containing the major B-and T-cell epitopes, respectively. To evaluate T-cell responses to the MSP1(33) fragment, two libraries of overlapping 18-mer peptides from the 3D7 and FVO MSP1(33) regions were used to screen a cohort of asymptomatic Kenyan adults. Gamma interferon (IFN-gamma) measured by enzyme-linked immunospot assay (ELISPOT) at multiple time points assessed the magnitude and stability of these responses. The percentage of individuals with IFN-gamma responses to single MSP1(33) peptides ranged from nil to 24%, were clustered among a subset of peptides, and were not consistently recalled over time. In comparison to peptide responses, IFN-gamma ELISPOT responses to recombinant MSP1(42) were more prevalent, more frequently elicited by the 3D7 as opposed to the FVO allele, and more stable over time. The prevailing MSP1(33) genotype infection was 3D7, with few mixed infections and no sole FVO infections. This study demonstrates that immunity against MSP1(33) after cumulative natural infections consists of low-magnitude and difficult-to-detect IFN-gamma responses. Although immunity against MSP1 alone will not confer protection against malaria, demonstrating a relative and sustained increase in T-cell immunity to MSP1 after vaccination would be a reasonable measurement of vaccine responsiveness. C1 [Spring, Michele D.; Tisch, Daniel J.; Kazura, James W.; Moormann, Ann M.] Case Western Reserve Univ, Ctr Global Hlth & Dis, Cleveland, OH 44106 USA. [Chelimo, Kiprotich; Sumba, Peter Odada] Kenya Govt Med Res Ctr, Kisumu, Kenya. [Tisch, Daniel J.] Case Western Reserve Univ, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA. [Rochford, Rosemary] SUNY Upstate Med Ctr, Syracuse, NY USA. [Long, Carole A.] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. RP Moormann, AM (reprint author), Univ Massachusetts, Med Sch Biotech 2, 373 Plantat St,Suite 318, Worcester, MA 01605 USA. EM ann.moormann@umassmed.edu FU National Institutes of Health [1R01-AI43906, 5R01-CA102667, FIC-1D43TW006576, T32-AI007427] FX This work was supported by National Institutes of Health, 1R01-AI43906 (J.W.K. and A.M.M.), 5R01-CA102667 (R.R.), FIC-1D43TW006576 (K.C. and P.O.S.), and T32-AI007427 (M.D.S.). NR 46 TC 6 Z9 6 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 OCT PY 2010 VL 78 IS 10 BP 4431 EP 4441 DI 10.1128/IAI.00415-10 PG 11 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 652KB UT WOS:000282004200035 PM 20696832 ER PT J AU Fishman, NO Henderson, DK AF Fishman, Neil O. Henderson, David K. CA Soc Healthcare Epidemiology Amer TI Letter in Response to the New SHEA Guideline for Healthcare Workers with Hepatitis B Virus, Hepatitis C Virus, and/or Human Immunodeficiency Virus Reply SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Letter ID PHYSICIANS; MANAGEMENT C1 [Fishman, Neil O.] Univ Penn, Sch Med, Philadelphia, PA 19104 USA. [Henderson, David K.] NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Fishman, NO (reprint author), 1300 Wilson Blvd,Suite 300, Arlington, VA 22209 USA. NR 8 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 0899-823X J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD OCT PY 2010 VL 31 IS 10 BP 1093 EP 1095 DI 10.1086/656560 PG 4 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 646SR UT WOS:000281563600022 ER PT J AU Eichacker, PQ Natanson, C AF Eichacker, Peter Q. Natanson, Charles TI Evaluating guidelines for critical care: a need for detail SO INTENSIVE CARE MEDICINE LA English DT Editorial Material ID CLINICAL-PRACTICE GUIDELINES; QUALITY C1 [Eichacker, Peter Q.; Natanson, Charles] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. RP Eichacker, PQ (reprint author), NIH, Dept Crit Care Med, Ctr Clin, Bldg 10,Room 2C145, Bethesda, MD 20892 USA. EM peichacker@mail.cc.nih.gov NR 9 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0342-4642 J9 INTENS CARE MED JI Intensive Care Med. PD OCT PY 2010 VL 36 IS 10 BP 1631 EP 1632 DI 10.1007/s00134-010-1978-2 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 651TN UT WOS:000281950100001 PM 20734188 ER PT J AU Fuhrman, BJ Xu, X Falk, RT Hankinson, SE Veenstra, TD Keefer, LK Ziegler, RG AF Fuhrman, Barbara J. Xu, Xia Falk, Roni T. Hankinson, Susan E. Veenstra, Timothy D. Keefer, Larry K. Ziegler, Regina G. TI Stability of 15 estrogens and estrogen metabolites in urine samples under processing and storage conditions typically used in epidemiologic studies SO INTERNATIONAL JOURNAL OF BIOLOGICAL MARKERS LA English DT Article DE Estradiol; Estrogen metabolites; Estrogens; Stability; Urine ID CHROMATOGRAPHY-MASS SPECTROMETRY; BREAST-CANCER RISK; AMERICAN WOMEN; HORMONE-LEVELS; REPRODUCIBILITY; PROFILE; ASSAY AB Background: In preparation for large-scale epidemiologic studies of the role of estrogen metabolism in the etiology of breast and other cancers, we examined the stability of estrogens and estrogen metabolites (EM) in urine during processing and storage protocols. Methods: Fifteen EM were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS) in first morning urines from 3 premenopausal women. Linear regression was used to model log EM concentrations for each woman, with and without adding ascorbic acid (0.1% w/v), during storage at 4 degrees C (7-8 time points, up to 48 hours), during long-term storage at -80 degrees C (10 time points, up to 1 year), and by freeze-thaw cycles (up to 3). Results: Without ascorbic acid, concentrations (pmol/mL) of nearly all EM changed <1% per 24 hours of storage at 4 degrees C, and <1% during storage at -80 degrees C for 1 year; similarly, thawing and refreezing samples 3 times was not consistently associated with losses for any EM. Ascorbic acid had no clear beneficial effect on EM stability in these experiments. Conclusions: Given the large inter-individual variability in urinary EM concentrations, changes of the magnitude observed here are unlikely to cause substantial misclassification. Furthermore, processing and storage conditions studied here are adequate for use in epidemiologic studies. C1 [Fuhrman, Barbara J.; Falk, Roni T.; Ziegler, Regina G.] NCI, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Xu, Xia; Veenstra, Timothy D.] NCI, Lab Prote & Analyt Technol, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21701 USA. [Hankinson, Susan E.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Hankinson, Susan E.] Harvard Univ, Sch Med, Boston, MA USA. [Keefer, Larry K.] NCI, Comparat Carcinogenesis Lab, Ctr Canc Res, Frederick, MD 21701 USA. RP Fuhrman, BJ (reprint author), NCI, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, Execut Plaza S,Room 5100, Bethesda, MD 20892 USA. EM fuhrmanb@mail.nih.gov RI Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 FU Center for Cancer Research, National Cancer Institute; Division of Cancer Epidemiology and Genetics, National Cancer Institute; National Institutes of Health; National Cancer Institute [N01-CO-12400] FX Financial support: This project has been funded by the Intramural Research Programs of the Center for Cancer Research and Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, and with federal funds from the National Cancer Institute under Contract N01-CO-12400 to SAIC-Frederick, Inc. NR 22 TC 8 Z9 8 U1 0 U2 4 PU WICHTIG EDITORE PI MILAN PA 72/74 VIA FRIULI, 20135 MILAN, ITALY SN 0393-6155 J9 INT J BIOL MARKER JI Int. J. Biol. Markers PD OCT-DEC PY 2010 VL 25 IS 4 BP 185 EP 194 DI 10.5301/JBM.2010.6086 PG 10 WC Biotechnology & Applied Microbiology; Oncology SC Biotechnology & Applied Microbiology; Oncology GA 700MU UT WOS:000285748300002 PM 21161939 ER PT J AU Mettu, RKR Wan, YW Habermann, JK Ried, T Guo, NL AF Mettu, Rama K. R. Wan, Ying-Wooi Habermann, Jens K. Ried, Thomas Guo, Nancy Lan TI A 12-gene genomic instability signature predicts clinical outcomes in multiple cancer types SO INTERNATIONAL JOURNAL OF BIOLOGICAL MARKERS LA English DT Article DE Genomic instability; Gene expression signatures; Breast cancer; Ovarian cancer; Colon cancer; Non-small cell lung cancer ID GENE-EXPRESSION SIGNATURE; II COLON-CANCER; BREAST-CANCER; PROGNOSTIC-SIGNIFICANCE; CARCINOMAS; CELLS; APOPTOSIS; SURVIVAL; TUMORS; LUNG AB Background and aims: Genomic instability, as reflected in specific chromosomal aneuploidies and variation in the nuclear DNA content, is a defining feature of human carcinomas. It is solidly established that the degree of genomic instability influences clinical outcome. We have recently identified a 12-gene expression signature that discerned genomically stable from unstable breast carcinomas. This gene expression signature was also useful to predict, with high accuracy, the clinical course in independent multiple published breast cancer cohorts. From a biological point of view, this result confirmed the central role of genomic instability for a tumor's ability to adapt to external challenges and selective pressure, and hence for continued survival fitness. This prompted us to investigate whether this genomic instability signature could also predict clinical outcome in other cancer types of epithelial origin, including colorectal tumors, non-small cell lung carcinomas, and ovarian cancer. Results: The results show that the gene expression signature that defines genomic instability and poor outcome in breast cancer contributes significantly more accurate (p<0.05 compared with random prediction) prognostic information in multiple cancer types independent of established clinical parameters. The 12-gene genomic instability signature stratified patients into high-and low-risk groups with distinct postoperative survival in three non-small cell lung cancer cohorts (n=637) in Kaplan-Meier analyses (log-rank p<0.05). It predicted recurrence in colon cancer patients (n=92) with an overall accuracy greater than 69% (p=0.04) in cross-cohort validation. It quantified relapse-free survival in ovarian cancer (n=124; log-rank p<0.05). Functional pathway analysis revealed interactions between the 12 signature genes and well-known cancer hallmarks. Conclusion: The degree of genomic instability has diagnostic and prognostic implications. It is tempting to speculate that pursuing genomic instability therapeutically could provide entry points for a target that is unique to cancer cells. C1 [Mettu, Rama K. R.; Wan, Ying-Wooi; Guo, Nancy Lan] W Virginia Univ, Mary Babb Randolph Canc Ctr Community Med, Morgantown, WV 26506 USA. [Habermann, Jens K.; Ried, Thomas] NCI, Genet Branch, NIH, Bethesda, MD 20892 USA. [Habermann, Jens K.] Univ Hosp Schleswig Holstein, Dept Surg, Lubeck, Germany. [Habermann, Jens K.] Karolinska Inst, Karolinska Biom Ctr, Stockholm, Sweden. RP Guo, NL (reprint author), W Virginia Univ, Mary Babb Randolph Canc Ctr Community Med, Morgantown, WV 26506 USA. EM riedt@mail.nih.gov; lguo@hsc.wvu.edu RI Habermann, Jens/E-2968-2010 FU National Cancer Institute; National Library of Medicine, NIH [R01LM009500]; NCRR, NIH [P20 RR16440] FX This research is supported by the following grants: T.R. by the National Cancer Institute (Intramural Research Program); N.L.G. by the National Library of Medicine (R01LM009500) and NCRR (P20 RR16440 and Supplement) from the NIH. NR 38 TC 12 Z9 12 U1 0 U2 6 PU WICHTIG EDITORE PI MILAN PA 72/74 VIA FRIULI, 20135 MILAN, ITALY SN 0393-6155 J9 INT J BIOL MARKER JI Int. J. Biol. Markers PD OCT-DEC PY 2010 VL 25 IS 4 BP 219 EP 228 DI 10.5301/JBM.2010.6079 PG 10 WC Biotechnology & Applied Microbiology; Oncology SC Biotechnology & Applied Microbiology; Oncology GA 700MU UT WOS:000285748300007 PM 21161944 ER PT J AU Farsaci, B Sabzevari, H Higgins, JP Di Bari, MG Takai, S Schlom, J Hodge, JW AF Farsaci, Benedetto Sabzevari, Helen Higgins, Jack P. Di Bari, Maria Giovanna Takai, Shinji Schlom, Jeffrey Hodge, James W. TI Effect of a small molecule BCL-2 inhibitor on immune function and use with a recombinant vaccine SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE vaccine; tumor immunotherapy; GX15-070; small molecule inhibitor; lung cancer ID CHRONIC LYMPHOCYTIC-LEUKEMIA; HUMAN CARCINOEMBRYONIC ANTIGEN; MIMETIC GX15-070 OBATOCLAX; T-CELL-ACTIVATION; PHASE-I; COSTIMULATORY MOLECULES; INFLUENZA NUCLEOPROTEIN; ESTABLISHED TUMORS; FAMILY INHIBITOR; PROSTATE-CANCER AB Small molecule BCL-2 inhibitors are being examined as monotherapy in phase I/II clinical trials for several types of tumors. However, few data are available about the effect of BCL-2 inhibitors on immune function. The aims of our study were to investigate the effect of a small molecule BCL-2 inhibitor on immune function and determine the most effective way of combining this inhibitor with a recombinant vaccine to treat tumors. The in vitro effect of the pan-BCL-2 inhibitor GX15-070 was assessed in mouse CD8 T lymphocytes at 2 different stages of activation as well as regulatory T lymphocytes (Treg). The in vivo effect of GX15-070 after recombinant vaccinia/fowlpox CEA-TRICOM vaccination was analyzed in tumor-infiltrating lymphocytes, and in splenocytes of mice bearing subcutaneous tumors. The therapeutic efficacy of such sequential therapy was measured as a reduction of pulmonary tumor nodules. Activated mature CD8 T lymphocytes were more resistant to GX15-070 as compared to early-activated cells. Treg function was significantly decreased after treatment with the BCL-2 inhibitor. In vivo, GX15-070 was given after vaccination so as to not negatively impact the induction of vaccine-mediated immunity, resulting in increased intratumoral activated CD8:Treg ratio and significant reduction of pulmonary tumor nodules. Our study is the first to show the effect of a small molecule BCL-2 inhibitor on the immune system and following a vaccine. It is also the first to demonstrate the efficacy of this sequence in reducing tumors in mouse models, providing a rationale for the design of combinational clinical studies. C1 [Farsaci, Benedetto; Sabzevari, Helen; Higgins, Jack P.; Di Bari, Maria Giovanna; Takai, Shinji; Schlom, Jeffrey; Hodge, James W.] NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Schlom, J (reprint author), NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, 10 Ctr Dr,Room 8B09, Bethesda, MD 20892 USA. EM js141c@nih.gov RI Farsaci, Benedetto/L-9837-2014; Hodge, James/D-5518-2015 OI Farsaci, Benedetto/0000-0001-8275-2561; Hodge, James/0000-0001-5282-3154 FU NIH FX Grant sponsor: NIH (Intramural Research Program) NR 38 TC 20 Z9 20 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0020-7136 EI 1097-0215 J9 INT J CANCER JI Int. J. Cancer PD OCT 1 PY 2010 VL 127 IS 7 BP 1603 EP 1613 DI 10.1002/ijc.25177 PG 11 WC Oncology SC Oncology GA 643ZM UT WOS:000281340200011 PM 20091862 ER PT J AU Fleisher, JM Fleming, LE Solo-Gabriele, HM Kish, JK Sinigalliano, CD Plano, L Elmir, SM Wang, JD Withum, K Shibata, T Gidley, ML Abdelzaher, A He, GQ Ortega, C Zhu, XF Wright, M Hollenbeck, J Backer, LC AF Fleisher, Jay M. Fleming, Lora E. Solo-Gabriele, Helena M. Kish, Jonathan K. Sinigalliano, Christopher D. Plano, Lisa Elmir, Samir M. Wang, John D. Withum, Kelly Shibata, Tomoyuki Gidley, Maribeth L. Abdelzaher, Amir He, Guoqing Ortega, Cristina Zhu, Xiaofang Wright, Mary Hollenbeck, Julie Backer, Lorraine C. TI The BEACHES Study: health effects and exposures from non-point source microbial contaminants in subtropical recreational marine waters SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Article DE Gastrointestinal illness; respiratory illness; skin illness; indicator organisms; enterococci; recreational water quality ID GASTROINTESTINAL ILLNESS; FECAL CONTAMINATION; DOMESTIC SEWAGE; COASTAL WATERS; QUALITY; GASTROENTERITIS; ENVIRONMENT; INDICATORS; RISK; GUIDELINES AB Methods A total of 1303 adult regular bathers were randomly assigned to bather and non-bather groups, with subsequent follow-up for reported illness, in conjunction with extensive environmental sampling of indicator organisms (enterococci). Results Bathers were 1.76 times more likely to report gastrointestinal illness [95% confidence interval (CI) 0.94-3.30; P = 0.07]; 4.46 times more likely to report acute febrile respiratory illness (95% CI 0.99-20.90; P = 0.051) and 5.91 times more likely to report a skin illness (95% CI 2.76-12.63; P < 0.0001) relative to non-bathers. Evidence of a dose-response relationship was found between skin illnesses and increasing enterococci exposure among bathers [1.46 times (95% CI 0.97-2.21; P = 0.07) per increasing log(10) unit of enterococci exposure], but not for gastrointestinal or respiratory illnesses. Conclusions This study indicated that bathers may be at increased risk of several illnesses relative to non-bathers, even in the absence of any known source of domestic sewage impacting the recreational marine waters. There was no dose-response relationship between gastroenteritis and increasing exposure to enterococci, even though many current water-monitoring standards use gastroenteritis as the major outcome illness. C1 [Fleisher, Jay M.] Nova SE Univ COM MPH, Ft Lauderdale, FL 33328 USA. [Fleisher, Jay M.; Fleming, Lora E.; Solo-Gabriele, Helena M.; Kish, Jonathan K.; Sinigalliano, Christopher D.; Plano, Lisa; Elmir, Samir M.; Wang, John D.; Withum, Kelly; Shibata, Tomoyuki; Gidley, Maribeth L.; Abdelzaher, Amir; He, Guoqing; Ortega, Cristina; Zhu, Xiaofang; Wright, Mary; Hollenbeck, Julie] Univ Miami, Rosenstiel Sch, Oceans & Human Hlth Ctr, NSF,NIEHS, Miami, FL USA. [Fleming, Lora E.; Plano, Lisa] Univ Miami, Miller Sch Med, Sch Med, Miami, FL 33136 USA. [Solo-Gabriele, Helena M.; Shibata, Tomoyuki; Abdelzaher, Amir; He, Guoqing; Ortega, Cristina; Wright, Mary] Univ Miami, Coll Engn, Coral Gables, FL 33124 USA. [Sinigalliano, Christopher D.; Shibata, Tomoyuki; Gidley, Maribeth L.] NOAA, Atlantic Oceanog & Meteorol Lab, Miami, FL 33149 USA. [Elmir, Samir M.] Miami Dade Cty Publ Hlth Dept, Miami, FL USA. [Backer, Lorraine C.] Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA USA. RP Fleisher, JM (reprint author), Nova SE Univ COM MPH, 3200 S Univ Dr, Ft Lauderdale, FL 33328 USA. EM jmfleish@nova.edu RI Sinigalliano, Christopher/A-8760-2014; gidley, maribeth/B-8335-2014 OI Sinigalliano, Christopher/0000-0002-9942-238X; gidley, maribeth/0000-0001-9583-8073 FU National Center for Environmental Health (NCEH), Centers for Disease Control and Prevention (CDC); Florida Dept of Health (FL DOH) through Florida Dept of Environmental Protection (FL DEP); EPA; National Science Foundation (NSF); National Institute of Environmental Health Sciences (NIEHS) Oceans and Human Health Center at the University of Miami Rosenstiel School [NSF 0CE0432368, NIEHS P50 ES12736]; NSF REU in Oceans and Human Health; NSF SGER in Oceans and Human Health [NSF SGER 0743987] FX National Center for Environmental Health (NCEH), Centers for Disease Control and Prevention (CDC); Florida Dept of Health (FL DOH) through monies from the Florida Dept of Environmental Protection (FL DEP); the EPA Internship Program; the National Science Foundation (NSF) and the National Institute of Environmental Health Sciences (NIEHS) Oceans and Human Health Center at the University of Miami Rosenstiel School (NSF 0CE0432368) and (NIEHS P50 ES12736) and NSF REU in Oceans and Human Health and the NSF SGER (NSF SGER 0743987) in Oceans and Human Health. NR 38 TC 54 Z9 58 U1 2 U2 18 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0300-5771 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD OCT PY 2010 VL 39 IS 5 BP 1291 EP 1298 DI 10.1093/ije/dyq084 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 676RA UT WOS:000283932000025 PM 20522483 ER PT J AU Minig, L Velazco, A Lamm, M Velez, JI Venturini, NC Testa, R AF Minig, Lucas Velazco, Andrea Lamm, Marina Velez, Jorge Ivan Caroppo Venturini, Nadia Testa, Roberto TI Evaluation of laparoscopic management of gynecologic emergencies by residents SO INTERNATIONAL JOURNAL OF GYNECOLOGY & OBSTETRICS LA English DT Article DE Gynecologic emergencies; Gynecologic endoscopy teaching; Laparoscopic treatment; Structured residency training endoscopy teaching curriculum ID ADNEXAL TORSION; ECTOPIC PREGNANCY; HOSPITAL STAY; SURGERY; PROGRAM; HEMOPERITONEUM; LAPAROTOMY; RISK AB Objective: To evaluate the feasibility of laparoscopic management of women with gynecologic emergencies by the residents and the chief resident in an organized resident training program. Methods: A retrospective study of patients with gynecologic emergencies who underwent laparoscopic surgery between January 1, 1999, and May 31, 2006 was done. Results: For the 369 patients included, the mean operative time of 74+/-31.35 minutes was significantly increased by advanced patient age (P<0.001), pelvic inflammatory disease with or without tuba-ovarian abscess (PID+/-TOA) (P<0.050), the first semester of chief residency (P<0.050), and conversion to laparotomy (P<0.001). Mean length of hospital stay was 40+/-24 hours. Factors such as advanced patient age (P<0.001), prolonged length of surgery (P<0.001), PID+/-TOA (P<0.001), first semester of chief residency (P<0.050), conversion to laparotomy (P<0.001), and blood transfusion (P<0.050) significantly increased the length of hospital stay. The conversion rate to laparotomy was 4.6% (n=17), and it was significantly associated with advanced women age (OR 1.11; 95% CI, 1.05-1.17, P<0.001) and PID+/-TOA (OR 6.04; 95%CI, 2.17-16.62, P<0.001). Postoperative complications were recorded in 3 (0.81%) patients. Conclusion: Laparoscopic management of gynecologic emergencies by senior residents and a chief resident within an organized resident training program is feasible. These results reinforce the relevance of a well-structured residency endoscopic training program. (C) 2010 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved. C1 [Minig, Lucas; Velazco, Andrea; Lamm, Marina; Caroppo Venturini, Nadia; Testa, Roberto] Hosp Italiano Buenos Aires, Dept Gynecol, Buenos Aires, DF, Argentina. [Minig, Lucas] Natl Canc Inst, Div Canc Treatment & Diag, NIH, Bethesda, MD USA. [Caroppo Venturini, Nadia] European Inst Oncol, Dept Gynecol, Prevent Unit Div, Milan, Italy. [Velez, Jorge Ivan] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. RP Minig, L (reprint author), Hosp Italiano Buenos Aires, Dept Gynecol, Buenos Aires, DF, Argentina. EM lucasminig@yahoo.com FU National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA FX This research was supported, in part, by the Intramural Research Program of the National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA. NR 22 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0020-7292 J9 INT J GYNECOL OBSTET JI Int. J. Gynecol. Obstet. PD OCT PY 2010 VL 111 IS 1 BP 62 EP 67 DI 10.1016/j.ijgo.2010.05.006 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 661NN UT WOS:000282735100015 PM 20579997 ER PT J AU Chen, M Voeller, D Marquez, VE Kaye, FJ Steeg, PS Giaccone, G Zajac-Kaye, M AF Chen, Min Voeller, Donna Marquez, Victor E. Kaye, Frederic J. Steeg, Patricia S. Giaccone, Giuseppe Zajac-Kaye, Maria TI Enhanced growth inhibition by combined DNA methylation/HDAC inhibitors in lung tumor cells with silenced CDKN2A SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE DNA methylation; HDAC inhibition; zebularine; depsipeptide; CDKN2A; lung cancer ID HISTONE DEACETYLASE INHIBITOR; CANCER-CELLS; 5-AZA-2'-DEOXYCYTIDINE DECITABINE; DEPSIPEPTIDE FR901228; EPIGENETIC THERAPY; CYTIDINE DEAMINASE; P16(INK4) PROTEIN; GENE-EXPRESSION; IN-VITRO; PHASE-I AB Aberrant hypermethylation at CpG sites within the CDKN2A gene is associated with silencing and has been proposed as a target for reactivation using both DNA methylation and histone deacetylation inhibitors. This study investigates the role of selecting tumor samples with a silenced as compared to deleted CDKN2A locus when assessing the efficacy of DNA methyltransferase inhibitor, zebularine, combined with the HDAC inhibitor, depsipeptide. Non-small cell lung cancer cell lines with defined CDKN2A status were analyzed by MTS assay to determine the effect of zebularine or zebularine combined with depsipeptide on tumor cell growth. We observed that zebularine treatment resulted in inhibition of cell growth in 11 out of 12 lung cancer cell lines with silenced CDKN2A, but no cell growth inhibition was detected in the 7 lung cancer cell lines tested with deleted CDKN2A (p>0.001). In addition, we found that the combination of 30 mu M zebularine and 6 or 7 nM depsipeptide resulted in a synergistic inhibition of cell growth in tumor cells with silenced CDKN2A (p<0.001, CI=0.70 and 0.57, respectively) but not in tumor cells with deleted CDKN2A. In conclusion, tumor cells with methylated CDKN2A are more sensitive to zebularine than cell lines with deleted CDKN2A and the combination of zebularine/depsipeptide results in a synergistic effect on cell growth inhibition that is also linked with the presence of silenced CDKN2A. Thus, combination of DNA methyltransferase and HDAC inhibitors may be a potential treatment for lung cancer patients, but careful selection of patients will be needed to optimize the benefit of this regimen. C1 [Zajac-Kaye, Maria] Univ Florida, Coll Med, Dept Med, Gainesville, FL 32610 USA. [Zajac-Kaye, Maria] Univ Florida, Dept Anat & Cell Biol, Gainesville, FL 32610 USA. [Chen, Min; Voeller, Donna; Giaccone, Giuseppe; Zajac-Kaye, Maria] NCI, Med Oncol Branch, Bethesda, MD 20892 USA. [Marquez, Victor E.] NCI, Med Chem Lab, Bethesda, MD 20892 USA. [Kaye, Frederic J.] NCI, Genet Branch, Bethesda, MD 20892 USA. [Steeg, Patricia S.] NCI, Pharmacol Lab, Bethesda, MD 20892 USA. RP Zajac-Kaye, M (reprint author), Univ Florida, Coll Med, Dept Med, Canc & Genet Res Complex,Room 360,2033 Mowry Rd, Gainesville, FL 32610 USA. EM mzajackaye@ufl.edu RI kaye, frederic/E-2437-2011; Giaccone, Giuseppe/E-8297-2017 OI Giaccone, Giuseppe/0000-0002-5023-7562 FU National Institutes of Health, National Cancer Institute; Department of Medicine and Department of Anatomy and Cell Biology of University of Florida, Gainesville, Florida FX We thank Carmen Allegra for critical reading of this manuscript and CTEP, DCTD, NCI for providing depsipeptide and zebularine. This research was supported, in part, by the Intramural Research Program of the National Institutes of Health, National Cancer Institute and by Department of Medicine and Department of Anatomy and Cell Biology of University of Florida, Gainesville, Florida. NR 47 TC 9 Z9 10 U1 0 U2 2 PU SPANDIDOS PUBL LTD PI ATHENS PA POB 18179, ATHENS, 116 10, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD OCT PY 2010 VL 37 IS 4 BP 963 EP 971 DI 10.3892/ijo_00000747 PG 9 WC Oncology SC Oncology GA 651HY UT WOS:000281920000023 PM 20811718 ER PT J AU Choong, NW Kozloff, M Taber, D Hu, HS Wade, J Ivy, P Karrison, TG Dekker, A Vokes, EE Cohen, EEW AF Choong, Nicholas W. Kozloff, Mark Taber, David Hu, H. Shawn Wade, James, III Ivy, Percy Karrison, Theodore G. Dekker, Allison Vokes, Everett E. Cohen, Ezra E. W. TI Phase II study of sunitinib malate in head and neck squamous cell carcinoma SO INVESTIGATIONAL NEW DRUGS LA English DT Article DE Head and neck cancer; Squamous cell carcinoma; Chemotherapy; Sunitinib; Multitargeted tyrosine kinase inhibitor ID ENDOTHELIAL-GROWTH-FACTOR; TYROSINE KINASE INHIBITOR; LYMPH-NODE METASTASIS; FACTOR-C; ANTITUMOR-ACTIVITY; FACTOR RECEPTORS; FACTOR-B; FACTOR-A; IN-VIVO; EXPRESSION AB Background Sunitinib is an orally administered multitargeted tyrosine kinase inhibitor of RET, VEGFR, PDGFR, and c-KIT. We conducted a phase II trial to evaluate the tolerability and efficacy of sunitinib in metastatic and/or recurrent SCCHN patients. Methods Patients who had received no more than two prior chemotherapy regimens were eligible and, depending on ECOG performance status (PS), were entered into either Cohort A (PS 0-1) or Cohort B (PS 2). Sunitinib was administered in 6-week cycles at 50 mg daily for 4 weeks followed by 2 weeks off. Primary endpoint for Cohort A was objective tumor response. A Simon two-stage design required twelve patients to be enrolled in the first stage and if 1 or fewer responses were observed, further study of this cohort would be terminated due to lack of treatment efficacy. Primary endpoint of Cohort B was to determine the feasibility of sunitinib in patients with ECOG performance status 2. Results Twenty-two patients were accrued (Cohort A - 15 patients, Cohort B - 7 patients). Median age in cohort A and B was 56 and 61 years, respectively. Grade 3 hematologic toxicities encountered were lymphopenia (18%), neutropenia (14%) and thrombocytopenia (5%). There was only one incidence of grade 4 hematologic toxicity which was thrombocytopenia. Fatigue and anorexia were the most common non-hematologic toxicities. Grade 3 fatigue occurred in 23% of patients. The only grade 4 non-hematologic toxicity was one incidence of gastrointestinal hemorrhage. Non-fatal hemorrhagic complications occurred in 8 patients: epistaxis (3 patients), pulmonary hemorrhage (2 patients), gastrointestinal hemorrhage (2 patients) and tumor hemorrhage (1 patient). Four patients were not evaluable for tumor response (Cohort A - 3patients, Cohort B - 1 pt). One partial response was observed in the entire study. Dose reduction was required in 5 patients (Cohort A - 3 patients for grd 3 fatigue, grd 3 mucositis and recurrent grd 3 neutropenia; Cohort B - 2 patients for grd 3 fatigue and grd 3 nausea). Median time to progression for cohort A and B were 8.4 and 10.5 weeks, respectively. Median overall survival for cohort A and B was 21 and 19 weeks, respectively. Conclusions Sunitinib had low single agent activity in SCCHN necessitating early closure of cohort A at interim analysis. Sunitinib was well tolerated in PS 2 patients. Further evaluation of single agent sunitinib in head and neck is not supported by the results of this trial. C1 [Choong, Nicholas W.; Cohen, Ezra E. W.] Univ Chicago, Med Ctr, Hematol Oncol Sect, Chicago, IL 60637 USA. [Choong, Nicholas W.; Dekker, Allison; Vokes, Everett E.; Cohen, Ezra E. W.] Univ Chicago, Med Ctr, Phase Network 2, Chicago, IL 60637 USA. [Choong, Nicholas W.] Med Coll Wisconsin, Div Neoplast Dis, Milwaukee, WI 53226 USA. [Kozloff, Mark] Ingalls Hosp, Harvey, IL 60430 USA. [Hu, H. Shawn] David C Pratt Canc Ctr, St Louis, MO 63141 USA. [Ivy, Percy] NCI, Invest Drug Branch, Canc Therapy Evaluat Program, Div Canc Treatments & Diag, Rockville, MD 20852 USA. [Karrison, Theodore G.] Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA. [Vokes, Everett E.; Cohen, Ezra E. W.] Univ Chicago, Canc Res Ctr, Chicago, IL 60637 USA. [Taber, David] Michiana Hematol Oncol, South Bend, IN 46601 USA. [Wade, James, III] Canc Care Specialists, Decatur, IL 62526 USA. RP Cohen, EEW (reprint author), Univ Chicago, Med Ctr, Hematol Oncol Sect, MC 2115,5841 S Maryland Ave, Chicago, IL 60637 USA. EM nchoong@mcw.edu; ecohen@medicine.bsd.uchicago.edu FU NIH [NO1 CM-07003-74]; UCCRC Cancer Center FX This study was supported by NIH Cooperative Contract NO1 CM-07003-74 and UCCRC Cancer Center Grant. NR 27 TC 38 Z9 38 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0167-6997 J9 INVEST NEW DRUG JI Invest. New Drugs PD OCT PY 2010 VL 28 IS 5 BP 677 EP 683 DI 10.1007/s10637-009-9296-7 PG 7 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 627UV UT WOS:000280069800016 PM 19649772 ER PT J AU Larrayoz, IM Huang, JD Lee, JW Pascual, I Rodriguez, IR AF Larrayoz, Ignacio M. Huang, Jiahn-Dar Lee, Jung Wha Pascual, Iranzu Rodriguez, Ignacio R. TI 7-Ketocholesterol-Induced Inflammation: Involvement of Multiple Kinase Signaling Pathways via NF kappa B but Independently of Reactive Oxygen Species Formation SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID SMOOTH-MUSCLE-CELLS; HUMAN ATHEROSCLEROTIC LESIONS; GROWTH-FACTOR EXPRESSION; LOW-DENSITY-LIPOPROTEIN; ENDOTHELIAL-CELLS; OXIDIZED LDL; HUMAN MACROPHAGES; PKC-ZETA; APOPTOSIS; OXYSTEROLS AB PURPOSE. 7-Ketocholesterol (7KCh) accumulates in oxidized lipoprotein deposits and is known to be involved in macrophage foam cell formation and atherosclerosis. 7-KCh is present in the primate retina and is associated with oxidized lipoprotein deposits located in the choriocapillaris, Bruch's membrane, and retinal pigment epithelium (RPE). 7-KCh can also be formed in the retina as a consequence of light-induced iron release. The purpose of this study was to examine the signaling pathways involved in the 7KCh-mediated inflammatory response focusing on three cytokines, VEGF, IL-6, and IL-8 METHODS. ARPE-19 cells were treated with 7KCh solubilized in hydroxypropyl-beta-cyclodextrin.Cytokines were quantified by qRT-PCR (mRNA) and ELISA (protein) using commercially available products. NF kappa B activation was determined by I kappa B alpha mRNA induction RESULTS. Treatment of ARPE-19 cells with 15 mu M 7KCh markedly induced the expression of VEGF, IL-6, and IL-8. No increase in NOX-4 expression or ROS formation was detected. 7KCh induced the phosphorylation of ERK1/2 and p38MAPK, and inhibitors to these kinases markedly reduced the cytokine expression but did not affect the I kappa B alpha mRNA expression. By contrast, inhibition of PI3K and PKC zeta significantly decreased the cytokine and I kappa B alpha mRNA expression. Inhibition of the I kappa B kinase complex essentially ablated all cytokine induction CONCLUSIONS. 7KCh induces cytokines via three kinase signaling pathways, AKT-PKC zeta-NF kappa B, p38 MAPK, and ERK. The MAPK/ERK pathways seem to preferentially enhance cytokine induction downstream from NF kappa B activation. The results of this study suggest that 7KCh activates these pathways through interactions in the plasma membrane, but the mechanism(s) remains unknown. (Invest Ophthalmol Vis Sci. 2010;51:4942-4955) DOI:10.1167/iovs.09-4854 C1 [Larrayoz, Ignacio M.; Huang, Jiahn-Dar; Lee, Jung Wha; Pascual, Iranzu; Rodriguez, Ignacio R.] NEI, NIH, Sect Mech Retinal Dis, LRCMB, Bethesda, MD 20892 USA. RP Rodriguez, IR (reprint author), NEI, NIH, Sect Mech Retinal Dis, LRCMB, 6 Ctr Dr,MSC0608, Bethesda, MD 20892 USA. EM rodriguezi@nei.nih.gov RI Larrayoz, Ignacio/I-5613-2012 OI Larrayoz, Ignacio/0000-0003-1629-152X FU National Eye Institute FX Supported by the National Eye Institute Intramural Research Program. NR 73 TC 29 Z9 30 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD OCT PY 2010 VL 51 IS 10 BP 4942 EP 4955 DI 10.1167/iovs.09-4854 PG 14 WC Ophthalmology SC Ophthalmology GA 655UI UT WOS:000282275500011 PM 20554621 ER PT J AU Wojciechowski, R Bailey-Wilson, JE Stambolian, D AF Wojciechowski, Robert Bailey-Wilson, Joan E. Stambolian, Dwight TI Association of Matrix Metalloproteinase Gene Polymorphisms with Refractive Error in Amish and Ashkenazi Families SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID MESSENGER-RNA LEVELS; TREE SHREW SCLERA; FORM-DEPRIVATION MYOPIA; OLD ORDER AMISH; OCULAR REFRACTION; HERITABILITY; LINKAGE; POPULATION; RECOVERY; GENOME AB PURPOSE. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are involved in scleral extracellular matrix remodeling and have shown differential expression in experimental myopia. The genetic association of refractive error and polymorphisms in MMP and TIMP genes in Old Order Amish (AMISH) and Ashkenazi Jewish (ASHK) families was investigated. METHODS. Individuals from 55 AMISH and 63 ASHK families participated in the study. Ascertainment was designed to enrich the families for myopia; the mean spherical equivalent (MSE) refractive error (SD) was -1.61 (2.72) D in the AMISH, and -3.56 (3.32) D in the ASHK. One hundred forty-six common haplotype tagging SNPs covering 14 MMP and 4 TIMP genes were genotyped in 358 AMISH and 535 ASHK participants. Association analyses of MSE and the spherical component of refraction (SPH) were performed separately for the AMISH and the ASHK. Bonferroni-corrected significance thresholds and local false discovery rates were used to account for multiple testing. RESULTS. After they were filtered for quality-control, 127 SNPs were included in the analyses. No polymorphisms showed statistically significant association to refraction in the ASHK (minimum P = 0.0132). In AMISH, two SNPs showed evidence of association with refractive phenotypes: rs1939008 (P = 0.00016 for SPH); and rs9928731 (P = 0.00026 for SPH). These markers were each estimated to explain <5% of the variance of SPH in the AMISH sample. CONCLUSIONS. Statistically significant genetic associations of ocular refraction to polymorphisms near MMP1 and within MMP2 were identified in the AMISH but not among the ASHK families. The results suggest that the MMP1 and MMP2 genes are involved in refractive variation in the AMISH. Genetic and/or environmental heterogeneity most likely contribute to differences in association results between ethnic groups. (Invest Ophthalmol Vis Sci. 2010;51:4989-4995) DOI:10.1167/iovs.10-5474 C1 [Wojciechowski, Robert; Bailey-Wilson, Joan E.] NHGRI, Inherited Dis Res Branch, NIH, Baltimore, MD 21224 USA. [Stambolian, Dwight] Univ Penn, Dept Ophthalmol, Philadelphia, PA 19104 USA. [Stambolian, Dwight] Univ Penn, Dept Genet, Philadelphia, PA 19104 USA. RP Wojciechowski, R (reprint author), NHGRI, Inherited Dis Res Branch, NIH, 333 Cassell Dr,Suite 1200, Baltimore, MD 21224 USA. EM robwoj@mail.nih.gov OI Bailey-Wilson, Joan/0000-0002-9153-2920; Wojciechowski, Robert/0000-0002-9593-4652 FU U.S. Public Health National Eye Institute [EY020483]; National Human Genome Research Institute, NIH; NIH [N01-HG-65403] FX Supported by U.S. Public Health National Eye Institute Grant EY020483 (DS) and in part by funds from the intramural program of the National Human Genome Research Institute, NIH (RW, JEB-W). Genotyping services were provided by the Center for Inherited Disease Research (CIDR) which is fully funded through Federal Contract N01-HG-65403 from the NIH to Johns Hopkins University. NR 48 TC 11 Z9 12 U1 0 U2 3 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD OCT PY 2010 VL 51 IS 10 BP 4989 EP 4995 DI 10.1167/iovs.10-5474 PG 7 WC Ophthalmology SC Ophthalmology GA 655UI UT WOS:000282275500017 PM 20484597 ER PT J AU Gallagher-Colombo, S Maminishkis, A Tate, S Grunwald, GB Philp, NJ AF Gallagher-Colombo, Shannon Maminishkis, Arvydas Tate, Susan Grunwald, Gerald B. Philp, Nancy J. TI Modulation of MCT3 Expression during Wound Healing of the Retinal Pigment Epithelium SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID MONOCARBOXYLATE TRANSPORTERS; NEURAL RETINA; CELLS; MEMBRANE; CD147; TISSUE; RPE; DIFFERENTIATION; GLYCOPROTEIN; BASIGIN AB PURPOSE. MCT3 is a proton-coupled monocarboxylate transporter preferentially expressed in the basolateral membrane of the retinal pigment epithelium (RPE) and has been shown to play an important role in regulating pH and lactate concentrations in the outer retina. Decreased expression of MCT3 in response to trauma or disease could contribute to pathologic changes in the retina. The present study followed the expression of MCT3 after wounding and re-epithelialization of chick RPE explant and human fetal (hf) RPE cultures. METHODS. Immunofluorescence microscopy and immunoblotting were performed to determine changes in MCT expression after scratch wounding and re-epithelialization of chick RPE/choroid explant cultures and hfRPE cell monolayers. RESULTS. MCT3 expression and basolateral polarity were maintained in chick RPE/choroid explant cultures and hfRPE monolayers. Wounding resulted in loss of MCT3 and the upregulation of MCT4 expression in migrating cells at the edge of the wound. On re-epithelialization, MCT3 was detected in chick and hfRPE cells when cells became hexagonally packed and pigmented. However, in hfRPE cells, MCT4 was consistently expressed throughout the epithelial monolayer. RPE cells at the edges of chick explants and hfRPE cultures with a free edge expressed MCT4 but not MCT3. CONCLUSIONS. Wounding of RPE monolayers resulted in dedifferentiation of the cells at the edge of the wound, as evidenced by a loss of MCT3 and increased MCT4 expression. Collectively, these findings suggest that both cell-cell and cell-substrate interactions are essential in directing and maintaining differentiation of the RPE and expression of MCT3. (Invest Ophthalmol Vis Sci. 2010;51:5343-5350) DOI:10.1167/iovs.09-5028 C1 [Gallagher-Colombo, Shannon; Tate, Susan; Grunwald, Gerald B.; Philp, Nancy J.] Thomas Jefferson Univ, Jefferson Med Coll, Dept Pathol Anat & Cell Biol, Philadelphia, PA 19107 USA. [Maminishkis, Arvydas] NEI, NIH, Bethesda, MD 20892 USA. RP Philp, NJ (reprint author), Thomas Jefferson Univ, Jefferson Med Coll, Dept Pathol Anat & Cell Biol, 1020 Locust St, Philadelphia, PA 19107 USA. EM nancy.philp@jefferson.edu OI Gallagher-Colombo, Shannon/0000-0001-5078-9431 FU National Eye Institute [EY012042, EY06658]; National Institutes on Alcohol Abuse and Alcoholism [AA07463] FX Supported by National Eye Institute Grants EY012042 (NJP) and EY06658 (GBG); and National Institutes on Alcohol Abuse and Alcoholism Training Grant AA07463 (SG-C). NR 29 TC 15 Z9 15 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD OCT PY 2010 VL 51 IS 10 BP 5343 EP 5350 DI 10.1167/iovs.09-5028 PG 8 WC Ophthalmology SC Ophthalmology GA 655UI UT WOS:000282275500063 PM 20505202 ER PT J AU Doyle, M Weinberg, N Pohost, GM Merz, CNB Shaw, LJ Sopko, G Fuisz, A Rogers, WJ Walsh, EG Johnson, BD Sharaf, BL Pepine, CJ Mankad, S Reis, SE Vido, DA Rayarao, G Bittner, V Tauxe, L Olson, MB Kelsey, SF Biederman, RWW AF Doyle, Mark Weinberg, Nicole Pohost, Gerald M. Merz, C. Noel Bairey Shaw, Leslee J. Sopko, George Fuisz, Anthon Rogers, William J. Walsh, Edward G. Johnson, B. Delia Sharaf, Barry L. Pepine, Carl J. Mankad, Sunil Reis, Steven E. Vido, Diane A. Rayarao, Geetha Bittner, Vera Tauxe, Lindsey Olson, Marian B. Kelsey, Sheryl F. Biederman, Robert W. W. TI Prognostic Value of Global MR Myocardial Perfusion Imaging in Women With Suspected Myocardial Ischemia and No Obstructive Coronary Disease Results From the NHLBI-Sponsored WISE (Women's Ischemia Syndrome Evaluation) Study SO JACC-CARDIOVASCULAR IMAGING LA English DT Article DE magnetic resonance; perfusion; women ID CARDIOVASCULAR MAGNETIC-RESONANCE; CARDIAC SYNDROME-X; ARTERY-DISEASE; CHEST-PAIN; HEART-DISEASE; PILOT PHASE; TASK-FORCE; CARDIOLOGY AB OBJECTIVES The purpose of this study was to assess the prognostic value of global magnetic resonance (MR) myocardial perfusion imaging (MPI) in women with suspected myocardial ischemia and no obstructive (stenosis <50%) coronary artery disease (CAD). BACKGROUND The prognostic value of global MR-MPI in women without obstructive CAD remains unknown. METHODS Women (n = 100, mean age 57 +/- 11 years, age range 31 to 76 years), with symptoms of myocardial ischemia and with no obstructive CAD, as assessed by coronary angiography, underwent MR-MPI and standard functional assessment. During follow-up (34 +/- 16 months), time to first adverse event (death, myocardial infarction, or hospitalization for worsening anginal symptoms) was analyzed using global MPI and left ventricular ejection fraction (EF) data. RESULTS Adverse events occurred in 23 (23%) women. Using univariable Cox proportional hazards regression modeling, variables found to be predictive of adverse events were global MR-MPI average uptake slope (p < 0.05), the ratio of MR-MPI peak signal amplitude to uptake slope (p < 0.05), and EF (p < 0.05). Two multivariable Cox models were formed, 1 using variables that were performance site dependent: ratio of MR-MPI peak amplitude to uptake slope together with EF (chi square: 13, p < 0.005); and a model using variables that were performance site independent: MR-MPI slope and EF (chi square: 12, p < 0.005). Each of the 2 multivariable models remained predictive of adverse events after adjustment for age, disease history, and Framingham risk score. For each of the Cox models, patients were categorized as high risk if they were in the upper quartile of the model and as not high risk otherwise. Kaplan-Meier analysis of time to event was performed for high risk versus not high risk for site-dependent (log rank: 15.2, p < 0.001) and site-independent (log rank: 13.0, p < 001) models. CONCLUSIONS Among women with suspected myocardial ischernia and no obstructive CAD, MR-MPI-determined global measurements of normalized uptake slope and peak signal uptake, together with global functional assessment of EF, appear to predict prognosis. (J Am Coll Cardiol Img 2010;3: 1030-6) (C) 2010 by the American College of Cardiology Foundation C1 [Doyle, Mark] Allegheny Gen Hosp, Div Cardiol, CV MRI Ctr, Pittsburgh, PA 15212 USA. [Sopko, George] NHLBI, NIH, Bethesda, MD 20892 USA. [Fuisz, Anthon] Washington Hosp Ctr, Dept Med, Washington, DC 20010 USA. [Pohost, Gerald M.] Univ So Calif, Keck Med Ctr, Los Angeles, CA USA. [Rogers, William J.; Bittner, Vera; Tauxe, Lindsey] Univ Alabama, Birmingham, AL USA. [Johnson, B. Delia; Reis, Steven E.; Olson, Marian B.; Kelsey, Sheryl F.] Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA. [Walsh, Edward G.; Sharaf, Barry L.] Brown Univ, Providence, RI 02912 USA. [Weinberg, Nicole; Merz, C. Noel Bairey; Shaw, Leslee J.] Cedars Sinai Med Ctr, Div Cardiol, Los Angeles, CA 90048 USA. [Pepine, Carl J.] Univ Florida, Gainesville, FL USA. RP Doyle, M (reprint author), Allegheny Gen Hosp, Div Cardiol, CV MRI Ctr, 320 East North Ave, Pittsburgh, PA 15212 USA. EM mdoyle@wpahs.org RI Library, Woodruff Health/A-6096-2012; Reis, Steven/J-3957-2014; OI Bittner, Vera/0000-0001-9456-850X FU National Heart, Lung, and Blood Institutes [N01-HV-68161, N01-HV-68162, N01-HV-68163, N01-HV-68164, RO1-HL-073412-01]; Gustavus and Louis Pfeiffer Research Foundation; [U0164829]; [U01 HL649141]; [U01 HL649241] FX This work was supported by contracts from the National Heart, Lung, and Blood Institutes, nos. N01-HV-68161, N01-HV-68162, N01-HV-68163, N01-HV-68164, and RO1-HL-073412-01, grants U0164829, U01 HL649141, and U01 HL649241, and grants from the Gustavus and Louis Pfeiffer Research Foundation, The Women's Guild of Cedars-Sinai Medical Center, The Ladies Hospital Aid Society of Western Pennsylvania, QMED, Inc., the Edythe L. Broad Endowment, and the Barbra Streisand Women's Cardiovascular Research and Education Program. Bracco Diagnostics, Inc. provided the ProH\ance contrast agent. The authors have reported that they have no relationships to disclose. H. William Strauss, MD, served as Guest Editor for this article. NR 23 TC 32 Z9 32 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-878X J9 JACC-CARDIOVASC IMAG JI JACC-Cardiovasc. Imag. PD OCT PY 2010 VL 3 IS 10 BP 1030 EP 1036 DI 10.1016/j.jcmg.2010.07.008 PG 7 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 672ED UT WOS:000283564900005 PM 20947048 ER PT J AU Lee, TH Chafets, DM Biggar, RJ McCune, JM Busch, MP AF Lee, Tzong-Hae Chafets, Daniel M. Biggar, Robert J. McCune, Joseph M. Busch, Michael P. TI The Role of Transplacental Microtransfusions of Maternal Lymphocytes in In Utero HIV Transmission SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HIV; maternal-fetal transmission; microchimerism; polymerase chain reaction; placenta ID MOTHER-TO-CHILD; IMMUNODEFICIENCY-VIRUS TYPE-1; POLYMERASE-CHAIN-REACTION; BLOOD COMPONENTS; FILTER-PAPER; TRIAL; MICROCHIMERISM; CONCORDANCE; ZIDOVUDINE; REGIMENS AB Background: The mechanisms of HIV transmission from mothers to infants are poorly understood. A possible mechanism of in utero transmission is transplacental transfer of HIV-infected maternal leukocytes into the fetal circulation during pregnancy. Objective: To determine if the frequency of in utero HIV infection correlates with presence or levels of maternal cells (MCs) in placenta-derived cord blood. Methods: DNA was extracted from dried cord blood spots (DBS) from newborns born to HIV+ mothers and corresponding maternal DBS specimens. Paired mother-infant samples were probed to identify unique maternal sequences targeted by 24 allele-specific real-time polymerase chain reaction assays. Infant DBS-derived DNA was then probed in replicate analyses for noninherited maternal allelic sequences. Rates of detection and levels of MCs in DBS samples of HIV(+) and HIV(-) newborns were compared. Results: Of 114 mother-infant pairs with informative alleles, 38 newborns were HIV(+) and 76 HIV(-), based on detection of HIV DNA/RNA at birth. MC were detected in 23 of 38 HIV(+) newborns (60.5%) and in 47 of 76 HIV(-) newborns (61.8%). The mean and median concentrations of nucleated MCs in DBS for the HIV(+)/MC(+) newborns (n = 23) were 0.33% and 0.27%, respectively, compared with 0.09% and 0.10% for the HIV(-)/MC(+) newborns (n = 47) (2-sample T test for means: P = 0.78). Conclusions: There was no significant difference in rates of detection or concentrations of MC in DBS between HIV(+) and HIV(-) newborns. Therefore, we could not demonstrate a correlation between MC in DBS, assumed to reflect levels of in utero maternal-fetal cell trafficking, and the risk of in utero HIV transmission. C1 [Lee, Tzong-Hae; Chafets, Daniel M.; Busch, Michael P.] UCSF, Blood Syst Res Inst, San Francisco, CA 94118 USA. [Biggar, Robert J.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Biggar, Robert J.] State Serum Inst, Dept Epidemiol Res, Copenhagen, Denmark. [McCune, Joseph M.] UCSF, Dept Med, Div Expt Med, San Francisco, CA 94118 USA. [Busch, Michael P.] UCSF, Dept Lab Med, San Francisco, CA 94118 USA. RP Busch, MP (reprint author), UCSF, Blood Syst Res Inst, 270 Masonic Ave, San Francisco, CA 94118 USA. EM mbusch@bloodsystems.org FU NHLBI [R01-HL-083388, R37 AI40312, DPI OD00329]; NIH FX These studies were supported in part by R01-HL-083388, NHLBI (D.M.C., T.H.L., and M.B.), R37 AI40312, and DPI OD00329 (J.M.M.). J.M.M. is a recipient of the NIH Director's Pioneer Award Program, part of the NIH Roadmap for Medical Research. NR 21 TC 5 Z9 6 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD OCT 1 PY 2010 VL 55 IS 2 BP 143 EP 147 DI 10.1097/QAI.0b013e3181eb301e PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 658QI UT WOS:000282504100007 PM 20683195 ER PT J AU Weinberg, A Song, LY Walker, R Allende, M Fenton, T Patterson-Bartlett, J Nachman, S Kemble, G Yi, TT Defechereux, P Wara, D Read, JS Levin, M AF Weinberg, Adriana Song, Lin-Ye Walker, Robert Allende, Maria Fenton, Terence Patterson-Bartlett, Julie Nachman, Sharon Kemble, George Yi, Ting-Ting Defechereux, Patricia Wara, Diane Read, Jennifer S. Levin, Myron CA IMPAACT P1057 Team TI Anti-Influenza Serum and Mucosal Antibody Responses After Administration of Live Attenuated or Inactivated Influenza Vaccines to HIV-Infected Children SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE antibodies; HIV-infected children; influenza vaccines; viral shedding ID CULTURE-CONFIRMED INFLUENZA; INTRAVENOUS-DRUG-USERS; YOUNG-CHILDREN; VIRUS VACCINE; EFFICACY; TRIVALENT; PREVENTION; SAFETY; IMMUNOGENICITY; IMMUNIZATION AB Background: Live-attenuated influenza vaccine (LAIV) prevents more cases of influenza in immune-competent children than the trivalent inactivated vaccine (TIV). We compared the antibody responses to LAIV or TIV in HIV-infected children. Methods: Blood and saliva obtained at enrollment, 4 and 24 weeks postimmunization from 243 HIV-infected children randomly assigned to TIV or LAIV were analyzed. Results: Both vaccines increased the anti-influenza neutralizing antibodies at 4 and 24 weeks postimmunization. At 4 weeks postimmunization, TIV recipients had 2-fold to 3-fold higher neutralizing antibody titers than LAIV recipients, but the proportions of subjects with protective titers (>= 1:40) were similar between treatment groups (96%-100% for influenza A and 81%-88% for influenza B). Both vaccines increased salivary homotypic IgG antibodies, but not IgA antibodies. Both vaccines also increased serum heterosubtypic antibodies. Among HIV-specific characteristics, the baseline viral load correlated best with the antibody responses to either vaccine. We used LAIV-virus shedding as a surrogate of influenza infection. Influenza-specific humoral and mucosal antibody levels were significantly higher in nonshedders than in shedders. Conclusions: LAIV and TIV generated homotypic and heterosubtypic humoral and mucosal antibody responses in HIV-infected children. High titers of humoral or mucosal antibodies correlated with protection against viral shedding. C1 [Weinberg, Adriana] Univ Colorado Denver, Clin Virol Lab, Dept Pediat, Aurora, CO 80045 USA. [Song, Lin-Ye; Fenton, Terence] Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA. [Walker, Robert; Allende, Maria; Kemble, George; Yi, Ting-Ting] MedImmune Inc, Gaithersburg, MD USA. [Nachman, Sharon] SUNY Stony Brook, Dept Pediat Infect Dis, Stony Brook, NY 11794 USA. [Defechereux, Patricia; Wara, Diane] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA. [Read, Jennifer S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA. RP Weinberg, A (reprint author), Univ Colorado Denver, Clin Virol Lab, Dept Pediat, Mail Stop 8604,12700 E 19th Ave,Room 11126, Aurora, CO 80045 USA. EM adriana.weinberg@ucdenver.edu FU National Center for Research Resources, NIH [5 MO1-RR00069]; National Institute of Allergy and Infectious Diseases [N01-HD-3-3162, U01AI068632, 1 U01 AI068616]; Eunice Kennedy Shriver National Institute of Child Health and Human Development [N01-HD-3-3345, N01-HD-33162]; MedImmune LLC FX Supported by grant number 5 MO1-RR00069, General Clinical Research Centers Program, National Center for Research Resources, NIH; N01-HD-3-3162 and by grant number U01AI068632 and 1 U01 AI068616 from the National Institute of Allergy and Infectious Diseases; and N01-HD-3-3345 and contract N01-HD-33162 (AW) from the Eunice Kennedy Shriver National Institute of Child Health and Human Development; and by MedImmune LLC. NR 29 TC 18 Z9 18 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 EI 1077-9450 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD OCT 1 PY 2010 VL 55 IS 2 BP 189 EP 196 DI 10.1097/QAI.0b013e3181e46308 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 658QI UT WOS:000282504100014 PM 20581690 ER PT J AU Levin, MJ Moscicki, AB Song, LY Fenton, T Meyer, WA Read, JS Handelsman, EL Nowak, B Sattler, CA Saah, A Radley, DR Esser, MT Weinberg, A AF Levin, Myron J. Moscicki, Anna-Barbara Song, Lin-Ye Fenton, Terrence Meyer, William A., III Read, Jennifer S. Handelsman, Edward L. Nowak, Barbara Sattler, Carlos A. Saah, Alfred Radley, David R. Esser, Mark T. Weinberg, Adriana CA IMPAACT P1047 Protocol Team TI Safety and Immunogenicity of a Quadrivalent Human Papillomavirus (Types 6, 11, 16, and 18) Vaccine in HIV-Infected Children 7 to 12 Years Old SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HPV vaccine; HIV infection; HPV antibody response ID SQUAMOUS INTRAEPITHELIAL LESIONS; IMMUNODEFICIENCY-VIRUS-INFECTION; ACTIVE ANTIRETROVIRAL THERAPY; RANDOMIZED CONTROLLED-TRIAL; PARTICLE VACCINE; RISK-FACTORS; YOUNG-WOMEN; NEUTRALIZING EPITOPES; ANTIBODY-RESPONSES; CLINICAL-TRIALS AB Background: Quadrivalent human papillomavirus vaccine (QHPV) is >95% effective in preventing infection with vaccine-type human papillomavirus. The safety and immunogenicity of QHPV are unknown in HIV-infected children. Methods: HIV-infected children (N = 126)-age >7 to <12 years, with a CD4% >= 15-and on stable antiretroviral therapy if CD4% was <25-were blindly assigned to receive a dose of QHPV or placebo (3: 1 ratio) at 0, 8, and 24 weeks. Adverse events were evaluated after each dose. Serum antibody against QHPV antigens was measured by a competitive Luminex immunoassay 1 month after the third QHPV dose. Results: The safety profile of QHPV was similar in the 2 study arms and to that previously reported for QHPV recipients. QHPV did not alter the CD4% or plasma HIV RNA. Seroconversion to all 4 antigens occurred in >96% of QHPV recipients and in no placebo recipients. Geometric mean titer was >27 to 262 times greater than the seropositivity cutoff value, depending on the antigen, but was 30%-50% lower against types 6 and 18 than those of age-similar historical controls. Conclusions: QHPV was safe and immunogenic in this cohort of HIV-infected children. Efficacy trials are warranted. C1 [Levin, Myron J.; Weinberg, Adriana] Univ Colorado Denver, Sch Med, Dept Pediat, Aurora, CO 80045 USA. [Moscicki, Anna-Barbara] Univ Calif San Francisco, Sch Med, Dept Pediat, San Francisco, CA 94143 USA. [Song, Lin-Ye; Fenton, Terrence] Harvard Univ, Sch Publ Hlth, Stat & Data Anal Ctr, Boston, MA 02115 USA. [Meyer, William A., III] Quest Diagnost, Baltimore, MD USA. [Read, Jennifer S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. [Handelsman, Edward L.] NIAID, NIH, Bethesda, MD 20892 USA. [Nowak, Barbara] Frontier Sci & Technol Res, Amherst, NY USA. [Sattler, Carlos A.; Saah, Alfred; Radley, David R.] Merck Res Labs, Wayne, PA USA. [Esser, Mark T.] PPD Vaccines & Biol Lab, N Wales, PA USA. RP Levin, MJ (reprint author), Univ Colorado Denver, Sch Med, Dept Pediat, Mail Stop C227,Bldg 401,1784 Racine St,Room R09-1, Aurora, CO 80045 USA. EM myron.levin@ucdenver.edu FU National Institute of Allergy and Infectious Diseases (NIAID) [U01 AI068632]; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); National Institute of Mental Health (NIMH) [AI068632]; Statistical and Data Analysis Center at Harvard School of Public Health under National Institute of Allergy and Infectious Diseases [5 U01 AI41110]; Pediatric AIDS Clinical Trials Group (PACTG); International Maternal Pediatric Adolescent AIDS Clinical Trials Group (IMPAACT) Group [1 U01 AI068616] FX Overall support for the International Maternal Pediatric Adolescent AIDS Clinical Trials Group (IMPAACT) was provided by the National Institute of Allergy and Infectious Diseases (NIAID) [U01 AI068632], the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), and the National Institute of Mental Health (NIMH) [AI068632]. Supported by the Statistical and Data Analysis Center at Harvard School of Public Health, under the National Institute of Allergy and Infectious Diseases cooperative agreement #5 U01 AI41110 with the Pediatric AIDS Clinical Trials Group (PACTG) and #1 U01 AI068616 with the International Maternal Pediatric Adolescent AIDS Clinical Trials Group (IMPAACT) Group. NR 42 TC 65 Z9 65 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD OCT 1 PY 2010 VL 55 IS 2 BP 197 EP 204 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 658QI UT WOS:000282504100015 PM 20574412 ER PT J AU Burstein, M Ginsburg, GS Tein, JY AF Burstein, Marcy Ginsburg, Golda S. Tein, Jenn-Yun TI Parental Anxiety and Child Symptomatology: An Examinzation of Additive and Interactive Effects of Parent Psychopathology SO JOURNAL OF ABNORMAL CHILD PSYCHOLOGY LA English DT Article DE Parent psychopathology symptoms; Child anxiety; Child depression; Child externalizing ID ANTISOCIAL-BEHAVIOR; HIGH-RISK; DEPRESSED MOTHERS; MAJOR DEPRESSION; PANIC DISORDER; FAMILY; TRANSMISSION; COMORBIDITY; ASSOCIATIONS; PREVALENCE AB The current study examined relations between parent anxiety and child anxiety, depression, and externalizing symptoms. In addition, the study tested the additive and interactive effects of parent anxiety with parent depression and externalizing symptoms in relation to child symptoms. Forty-eight parents with anxiety disorders and 49 parents without any psychiatric disorder participated with one of their children (ages 6 to 14 years; 46.4% male; 75.8% Caucasian). Parent anxiety was related to both child anxiety and depression, but not child externalizing symptoms. Hierarchical regression analyses showed that only parent externalizing symptoms had additive effects, beyond parent anxiety symptoms, in relation to child anxiety symptoms. Further, parent anxiety symptoms moderated the relationship between parent and child externalizing symptoms, such that the strength of this relationship was reduced in the presence of high levels of parent anxiety symptoms. Results of this study illuminate the role of parent comorbidity in understanding relations between parent and child symptoms. C1 [Burstein, Marcy; Ginsburg, Golda S.] Johns Hopkins Univ Hosp, Div Child & Adolescent Psychiat, Sch Med, Baltimore, MD 21287 USA. [Tein, Jenn-Yun] Arizona State Univ, Prevent Res Ctr, Tempe, AZ 85287 USA. RP Burstein, M (reprint author), NIMH, Sect Dev Genet Epidemiol, 35 Convent Dr,Bldg 35,Room 1A104,MSC 3720, Bethesda, MD 20814 USA. EM bursteinme@mail.nih.gov FU NIMH NIH HHS [K23 MH063427, K23MH6342702, R01 MH077312, T32MH020033] NR 57 TC 21 Z9 21 U1 1 U2 8 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0091-0627 J9 J ABNORM CHILD PSYCH JI J. Abnorm. Child Psychol. PD OCT PY 2010 VL 38 IS 7 BP 897 EP 909 DI 10.1007/s10802-010-9415-0 PG 13 WC Psychology, Clinical; Psychology, Developmental SC Psychology GA 655SD UT WOS:000282268900002 PM 20432062 ER PT J AU Gungor, D Bornstein, MH AF Gungor, Derya Bornstein, Marc H. TI Culture-general and -specific associations of attachment avoidance and anxiety with perceived parental warmth and psychological control among Turk and Belgian adolescents SO JOURNAL OF ADOLESCENCE LA English DT Article DE Adolescents; Peer attachment; Psychological control; Parental warmth; Attachment styles; Culture ID CLOSE RELATIONSHIPS; PEER RELATIONS; YOUNG-ADULTS; ADJUSTMENT; SELF; STYLES; REPRESENTATIONS; PATTERNS; MODELS; PERFECTIONISM AB Both the adolescent peer attachment and perceived parenting style literatures emphasize the role of the quality of the parent-child relationship in children's healthy adjustment beyond the family, but few studies have investigated links between adolescents' peer attachment and perceptions of parenting. We investigate relations of adolescents' perceptions of warmth and psychological control from parents with avoidance and anxiety in attachment to close friends in two contrasting cultures. Altogether, 262 Turk and 263 Belgian youth between 14 and 18 years of age participated. Cross-culturally, attachment avoidance was negatively related to maternal warmth, and attachment anxiety positively related to maternal and paternal control and negatively to paternal warmth. Beyond these general relations, attachment avoidance was associated with paternal psychological control in Belgians but not in Turks. The study provides cross-cultural evidence for specific relations between peer attachment and perceived parenting and suggests a culture-specific pathway for the development of attachment avoidance. (C) 2009 The Association for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved. C1 [Gungor, Derya] Katholieke Univ Leuven, Ctr Social & Cultural Psychol, B-3000 Louvain, Belgium. [Bornstein, Marc H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Dept Hlth & Human Serv, Eunice, LA USA. RP Gungor, D (reprint author), Katholieke Univ Leuven, Ctr Social & Cultural Psychol, Tiensestr 102 Bus 03727, B-3000 Louvain, Belgium. EM Derya.Gungor@psy.kuleuven.be FU Intramural NIH HHS NR 50 TC 9 Z9 11 U1 3 U2 23 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0140-1971 J9 J ADOLESCENCE JI J. Adolesc. PD OCT PY 2010 VL 33 IS 5 BP 593 EP 602 DI 10.1016/j.adolescence.2009.12.005 PG 10 WC Psychology, Developmental SC Psychology GA 670EX UT WOS:000283405100003 PM 20079527 ER PT J AU Madkour, AS Farhat, T Halpern, CT Godeau, E Gabhainn, SN AF Madkour, Aubrey S. Farhat, Tilda Halpern, Carolyn T. Godeau, Emmanuelle Gabhainn, Saoirse N. TI Early Adolescent Sexual Initiation as a Problem Behavior: A Comparative Study of Five Nations SO JOURNAL OF ADOLESCENT HEALTH LA English DT Article DE Adolescent; Sexual behavior; Problem behavior theory; Cross-national ID RISK BEHAVIOR; FAMILY-STRUCTURE; HEALTH BEHAVIOR; INTERCOURSE; ADULTHOOD; DRINKING; DECISION; DEBUT; GIRLS AB Purpose: Using a Problem Behavior Theory framework, this article examines the extent to which psychosocial correlates of early sexual initiation (before age 16) vary across developed nations. Methods: Fifteen-year-old participants (n = 5,624) in the 1997-1998 World Health Organization collaborative Health Behavior in School-Aged Children survey (Finland, Scotland, France, and Poland) and the 1996 U.S. Add Health survey self-reported substance use (alcohol and tobacco), school attachment, positive parental communication, and early sexual intercourse experience. Stratifying by gender, we performed univariate, bivariate, and multivariable analyses controlling for family socioeconomic status, family structure, and nation fixed effects. Results: Self-reported early sexual experience, substance use, school attachment, and positive communication with parents varied significantly across nations for both boys and girls. In both crude and adjusted analyses, substance use was positively associated with early sexual experience among boys and girls across nations, although associations were stronger in Europe than in the United States (adjusted odds ratio [AOR]; range, 1.56-3.74). School attachment was similarly inversely related to early sexual experience among boys and girls across nations (AOR range, .63.94). However, positive parent communication was significantly inversely related to early sexual experience only among U.S. females (AOR .50). Conclusions: Findings overall supported the fit of early adolescent sexual initiation as a risk behavior within a Problem Behavior Theory framework cross-nationally, suggesting that similar factors could be targeted to prevent early sexual initiation across some developed nations. However, further research is warranted examining the temporality of these relationships. (C) 2010 Society for Adolescent Health and Medicine. All rights reserved. C1 [Madkour, Aubrey S.] Tulane Sch Publ Hlth & Trop Med, Dept Community Hlth Sci, New Orleans, LA 70112 USA. [Farhat, Tilda] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Prevent Res Branch, Div Epidemiol Stat & Prevent Res, Bethesda, MD USA. [Halpern, Carolyn T.] Univ N Carolina, Dept Maternal & Child Hlth, Chapel Hill, NC USA. [Halpern, Carolyn T.] Univ N Carolina, Carolina Populat Ctr, Chapel Hill, NC USA. [Godeau, Emmanuelle] Univ Toulouse 3, INSERM, UMR, U558, Toulouse, France. [Godeau, Emmanuelle] Serv Med Rectorat Acad Toulouse, Toulouse, France. [Gabhainn, Saoirse N.] Natl Univ Ireland, Sch Hlth Sci, Hlth Promot Res Ctr, Galway, Ireland. RP Madkour, AS (reprint author), Tulane Sch Publ Hlth & Trop Med, Dept Community Hlth Sci, 1440 Canal St,TW-19, New Orleans, LA 70112 USA. EM aspriggs@tulane.edu FU Eunice Kennedy Shriver National Institute of Child Health and Human Development [P01-HD31921]; Carolina Population Center, NICHD NRSA [NIH-NICHD T32-HD07168] FX This research uses data from Add Health, a program project designed by J. Richard Udry, Peter S. Bearman, and Kathleen Mullan Harris, and funded by a grant P01-HD31921 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, with cooperative funding from 17 other agencies. Special acknowledgment is due Ronald R. Rindfuss and Barbara Entwisle for assistance in the original design. Persons interested in obtaining data files from Add Health should contact Add Health, Carolina Population Center, 123 W. Franklin Street, Chapel Hill, NC 27516-2524 (addhealth@unc.edu). No direct support was received from grant P01-HD31921 for this analysis.; Dr. Madkour's time on this project was partially supported by the Carolina Population Center, NICHD NRSA predoctoral traineeship, grant number NIH-NICHD T32-HD07168. An earlier version of this manuscript was presented at the 2009 Population Association of America Annual Meeting. NR 37 TC 38 Z9 41 U1 0 U2 16 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1054-139X J9 J ADOLESCENT HEALTH JI J. Adolesc. Health PD OCT PY 2010 VL 47 IS 4 BP 389 EP 398 DI 10.1016/j.jadohealth.2010.02.008 PG 10 WC Psychology, Developmental; Public, Environmental & Occupational Health; Pediatrics SC Psychology; Public, Environmental & Occupational Health; Pediatrics GA 653QT UT WOS:000282112500011 PM 20864009 ER PT J AU Mueller-Pfeiffer, C Martin-Soelch, C Blair, JR Carnier, A Kaiser, N Rufer, M Schnyder, U Hasler, G AF Mueller-Pfeiffer, C. Martin-Soelch, C. Blair, J. R. Carnier, A. Kaiser, N. Rufer, M. Schnyder, U. Hasler, G. TI Impact of emotion on cognition in trauma survivors: What is the role of posttraumatic stress disorder? SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE Posttraumatic stress disorder; Stress disorders; Anxiety disorders; Behavior; Emotion regulation; Attention ID ATTENTION; PERFORMANCE; ANXIETY AB Background: Cognitive theories of anxiety disorders postulate an increased attentional bias to environmental cues associated with threat that underlies the exaggerated fear response. The role of trauma, which may represent strong competitive advantage for attention, remains unclear. We investigated the influence of trauma exposure and the presence of anxiety/stress disorders on the impact of emotional distractors on cognitive performance. Methods: Fourteen trauma-exposed subjects with PTSD, 12 trauma-exposed subjects with anxiety disorders other than PTSD, 12 trauma-exposed healthy subjects and 19 non-trauma-exposed healthy controls participated in this study. The impact of emotion on cognition was determined by the Affective Stroop task that measures the effect of irrelevant emotional distractors on the speed of operant responding. Results: The speed of cognitive performance was significantly reduced in the presence of negative distractors versus neutral or positive distractors in subjects with PTSD, while there was no significant influence of the distractor type on performance in the other diagnostic groups (diagnosis-by-distractor type interaction, p<0.001). While negative distractors induced the same levels of anxiety and depersonalization in subjects with PTSD and subjects with other anxiety disorders, distractor-induced depersonalization was associated with slowing of cognitive performance in PTSD (p = 0.02) but not in other groups. Limitations: Different types of anxiety disorders in the non-PTSD group might reduce the selectivity of the results; some subjects received medication possibly impacting on their cognitive functioning. Conclusions: The cognitive impairments in the presence of negative distractors specifically found in PTSD call for research into novel psychotherapeutic approaches, e.g. attentional training, for PTSD. (C) 2010 Elsevier By. All rights reserved. C1 [Mueller-Pfeiffer, C.; Martin-Soelch, C.; Carnier, A.; Rufer, M.; Schnyder, U.] Univ Zurich Hosp, Dept Psychiat, CH-8091 Zurich, Switzerland. [Mueller-Pfeiffer, C.] Ctr Educ & Res COEUR, Psychiat Serv Cty St Gallen N, CH-9500 Wil, Switzerland. [Blair, J. R.] NIMH, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA. [Kaiser, N.] Clienia Littenheid AG, Dept Psychotherapy, CH-9573 Littenheid, Switzerland. [Hasler, G.] Psychiat Univ Hosp, CH-3000 Bern 60, Switzerland. RP Mueller-Pfeiffer, C (reprint author), Univ Zurich Hosp, Dept Psychiat, Culmannstr 8, CH-8091 Zurich, Switzerland. EM christoph.mueller-pfeiffer@access.uzh.ch; g.hasler@bluewin.ch RI Hasler, Gregor/E-4845-2012; OI Hasler, Gregor/0000-0002-8311-0138; Rufer, Michael/0000-0003-4964-4213 FU Department of Psychiatry, University Hospital, Zurich, Switzerland FX There was no external study sponsor. Funding for this study was provided by internal means of the Department of Psychiatry, University Hospital, Zurich, Switzerland. NR 20 TC 19 Z9 20 U1 1 U2 17 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD OCT PY 2010 VL 126 IS 1-2 BP 287 EP 292 DI 10.1016/j.jad.2010.03.006 PG 6 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 658KD UT WOS:000282488000039 PM 20417971 ER PT J AU Liu, AH Jaramillo, R Sicherer, SH Wood, RA Bock, SA Burks, AW Massing, M Cohn, RD Zeldin, DC AF Liu, Andrew H. Jaramillo, Renee Sicherer, Scott H. Wood, Robert A. Bock, S. Allan Burks, A. Wesley Massing, Mark Cohn, Richard D. Zeldin, Darryl C. TI National prevalence and risk factors for food allergy and relationship to asthma: Results from the National Health and Nutrition Examination Survey 2005-2006 SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Asthma; eczema; egg; food allergy; food sensitization; food-specific serum IgE; peanut; hay fever; milk; prevalence; risk; shrimp ID UNITED-STATES; IGE CONCENTRATIONS; TELEPHONE SURVEY; CHILDREN; CHALLENGES; LIFE; HYPERSENSITIVITY; POPULATION; REACTIVITY; EXERCISE AB Background: The national prevalence and patterns of food allergy (FA) in the United States are not well understood. Objective: We developed nationally representative estimates of the prevalence of and demographic risk factors for FA and investigated associations of FA with asthma, hay fever, and eczema. Methods: A total of 8203 participants in the National Health and Nutrition Examination Survey 2005-2006 had food-specific serum IgE measured to peanut, cow's milk, egg white, and shrimp. Food-specific IgE and age-based criteria were used to define likely FA (LFA), possible FA, and unlikely FA and to develop estimates of clinical FA. Self-reported data were used to evaluate demographic risk factors and associations with asthma and related conditions. Results: In the United States, the estimated prevalence of clinical FA was 2.5% (peanut, 1.3%; milk, 0.4%; egg, 0.2%; shrimp, 1.0%; not mutually exclusive). Risk of possible FA/LFA was increased in non-Hispanic blacks (odds ratio, 3.06; 95% CI, 2.14-4.36), males (1.87; 1.32-2.66), and children (2.04; 1.42-2.93). Study participants with doctor-diagnosed asthma (vs no asthma) exhibited increased risk of all measures of food sensitization. Moreover, in those with LFA, the adjusted odds ratio for current asthma (3.8; 1.5-10.7) and an emergency department visit for asthma in the past year (6.9; 2.4-19.7) were both notably increased. Conclusion: Population-based serologic data on 4 foods indicate an estimated 2.5% of the US population has FA, and increased risk was found for black subjects, male subjects, and children. In addition, FA could be an under-recognized risk factor for problematic asthma. (J Allergy Clin Immunol 2010;126:798-806.) C1 [Liu, Andrew H.; Bock, S. Allan] Natl Jewish Hlth, Denver, CO 80206 USA. [Liu, Andrew H.; Bock, S. Allan] Univ Colorado, Denver Sch Med, Denver, CO 80202 USA. [Jaramillo, Renee; Massing, Mark; Cohn, Richard D.] SRA Int Inc, Durham, NC USA. [Sicherer, Scott H.] Mt Sinai Sch Med, Jaffe Food Allergy Inst, New York, NY USA. [Wood, Robert A.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Burks, A. Wesley] Duke Univ, Med Ctr, Durham, NC USA. [Zeldin, Darryl C.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA. RP Liu, AH (reprint author), Natl Jewish Hlth, 1400 Jackson St K1023, Denver, CO 80206 USA. EM liua@njhealth.org RI Osborne, Nicholas/N-4915-2015 OI Osborne, Nicholas/0000-0002-6700-2284 FU NIH, National Institute of Environmental Health Sciences; NIH/NIAID; Food Allergy Initiative; FAAN; NIH; National Jewish Health; Food Allergy and the Anaphylaxis Network; Wallace Research Foundation FX Supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences.; Disclosure of potential conflict of interest: S. H. Sicherer is a consultant for the Food Allergy Initiative and has received research support from NIH/NIAID, Food Allergy Initiative, and FAAN. R. A. Wood has received research support from the NIH and is on the medical advisory board for FAAN. S. A. Bock has received research support from National Jewish Health. A. W. Burks is a consultant for ActoGeniX NV, Intelliject, McNeil Nutritionals, and Novartis; is a minority stockholder for Allertein and MastCell Inc; is on the advisory board for Dannon CO Probiotics; is on the expert panel for Nutricia; has received research support from the National Institutes of Health, the Food Allergy and the Anaphylaxis Network, and the Wallace Research Foundation; has served as an expert witness on the topic of food allergies; is on the medical board of directors for FAAN; is on the Dermatological Allergy Committee for the ACAAI; is a Study Section Member for the NIH/HAI; and is on the reviewer board for the Journal of Allergy and Clinical Immunology and the FDA. The rest of the authors have declared that they have no conflict of interest. NR 31 TC 194 Z9 200 U1 4 U2 19 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD OCT PY 2010 VL 126 IS 4 BP 798 EP U186 DI 10.1016/j.jaci.2010.07.026 PG 22 WC Allergy; Immunology SC Allergy; Immunology GA 658SP UT WOS:000282510000018 PM 20920770 ER PT J AU Roufosse, F de Lavareille, A Schandene, L Cogan, E Georgelas, A Wagner, L Xi, LQ Raffeld, M Goldman, M Gleich, GJ Klion, A AF Roufosse, Florence de Lavareille, Aurore Schandene, Liliane Cogan, Elie Georgelas, Ann Wagner, Lori Xi, Liqiang Raffeld, Mark Goldman, Michel Gleich, Gerald J. Klion, Amy TI Mepolizumab as a corticosteroid-sparing agent in lymphocytic variant hypereosinophilic syndrome SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE CD3(-)CD4(+); lymphocytic variant HES; clonal T-cell; TARC; IL-5; mepolizumab ID ACTIVATION-REGULATED CHEMOKINE; T-CELLS; IDIOPATHIC EOSINOPHILIA; DISEASE-ACTIVITY; SERUM THYMUS; INTERLEUKIN-5; TARC/CCL17; EXPRESSION; LEVEL; TARC AB Background: Mepolizumab, a monoclonal anti-IL-5 antibody, is an effective corticosteroid-sparing agent for patients with Fip1-like 1/platelet-derived growth factor receptor a fusion (F/P)-negative hypereosinophilic syndrome (HES). Lymphocytic variant hypereosinophilic syndrome (L-HES) is characterized by marked overproduction of IL-5 by dysregulated T cells. Objective: To determine whether patients with L-HES respond to mepolizumab in terms of corticosteroid tapering and eosinophil depletion to the same extent as corticosteroid-responsive F/P-negative patients with HES and a normal T-cell profile. Methods: Patients enrolled in the mepolizumab trial were evaluated for L-HES on the basis of T-cell phenotyping and T-cell receptor gene rearrangement patterns, and their serum thymus-and-activation-regulated chemokine (TARC) levels were measured. Response to treatment was compared in patient subgroups based on results of these analyses. Results: Lymphocytic variant HES was diagnosed in 13 of 63 patients with HES with complete T-cell assessments. The ability to taper corticosteroids on mepolizumab was similar in patients with L-HES and those with a normal T-cell profile, although a lower proportion of patients with L-HES maintained eosinophil levels below 600/mu L. Increased serum TARC levels (> 1000 pg/mL) had no significant impact on the ability to reduce corticosteroid doses, but a lower proportion of patients with elevated TARC achieved eosinophil control on mepolizumab. Conclusion: Mepolizumab is an effective corticosteroid-sparing agent for patients with L-HES. In some cases however, eosinophil levels remain above 600/mL, suggesting incomplete neutralization of overproduced IL-5 or involvement of other eosinophilopoietic factors. (J Allergy Clin Immunol 2010;126:828-35.) C1 [Roufosse, Florence; Cogan, Elie] Univ Libre Bruxelles, Erasme Hosp, Dept Internal Med, B-1070 Brussels, Belgium. [de Lavareille, Aurore; Schandene, Liliane] Univ Libre Bruxelles, Erasme Hosp, Immunol Lab, B-1070 Brussels, Belgium. [Roufosse, Florence; Goldman, Michel] Univ Libre Bruxelles, Inst Med Immunol, Gosselies, Belgium. [Georgelas, Ann; Wagner, Lori; Gleich, Gerald J.] Univ Utah, Dept Dermatol, Salt Lake City, UT USA. [Gleich, Gerald J.] Univ Utah, Dept Med & Pediat, Salt Lake City, UT USA. [Xi, Liqiang; Raffeld, Mark] NCI, Pathol Lab, Bethesda, MD 20892 USA. [Klion, Amy] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Roufosse, F (reprint author), Univ Libre Bruxelles, Erasme Hosp, Dept Internal Med, 808 Route Lennik, B-1070 Brussels, Belgium. EM froufoss@ulb.ac.be OI Klion, Amy/0000-0002-4986-5326 FU Belgian National Fund for Scientific Research (FNRS) [3.4.582.05.4, 7.4.573.08]; David and Alice Van Buuren Foundation (Universite Libre de Bruxelles); National Institutes of Health; National Cancer Institute [AI-061097]; National Institute of Allergy and Infectious Diseases; GlaxoSmithKline FX GlaxoSmithKline purchased the mAbs for flow cytometry and sponsored the MHE100185 clinical trial (Clinicaltrials.gov identifier: NCT00086658) through which patients were recruited for the current study. This study was supported by the Belgian National Fund for Scientific Research (FNRS) through FRSM grant 3.4.582.05.4 and Televie grant 7.4.573.08. F and received funding from the David and Alice Van Buuren Foundation (Universite Libre de Bruxelles). This work was supported, in part, by the Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases and National Cancer Institute, and work at the University of Utah was supported through National Institutes of Health grant AI-061097.; Disclosure of potential conflict of interest: F. Roufosse, L. Schandene, and A. Georgelas have received research support from GlaxoSmithKline. G. J. Gleich is an equity holder of Ception Therapeutics and has received research support from GlaxoSmithKline. The rest of the authors have declared that they have no conflict of interest. NR 22 TC 34 Z9 36 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD OCT PY 2010 VL 126 IS 4 BP 828 EP U240 DI 10.1016/j.jaci.2010.06.049 PG 11 WC Allergy; Immunology SC Allergy; Immunology GA 658SP UT WOS:000282510000022 PM 20810155 ER PT J AU Concheiro, M Jones, HE Johnson, RE Choo, R Shakleya, DM Huestis, MA AF Concheiro, Marta Jones, Hendree E. Johnson, Rolley E. Choo, Robin Shakleya, Diaa M. Huestis, Marilyn A. TI Umbilical Cord Monitoring of In Utero Drug Exposure to Buprenorphine and Correlation with Maternal Dose and Neonatal Outcomes SO JOURNAL OF ANALYTICAL TOXICOLOGY LA English DT Article ID PREGNANT-WOMEN; AMNIOTIC-FLUID; FETAL EXPOSURE; HUMAN MECONIUM; COCAINE; TISSUE; METABOLITES; METHADONE; MATRICES; ABUSE C1 [Huestis, Marilyn A.] NIDA, IRP, NIH, BRC, Baltimore, MD 21224 USA. [Concheiro, Marta] Univ Santiago de Compostela, Dept Anat Patol & Ciencias Forenses, Santiago De Compostela, Spain. [Jones, Hendree E.; Johnson, Rolley E.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. [Johnson, Rolley E.] Reckitt Benckiser Pharmaceut Inc, Richmond, VA USA. [Choo, Robin] Univ Pittsburgh, Dept Nat Sci, Titusville, PA USA. RP Huestis, MA (reprint author), NIDA, IRP, NIH, BRC, 251 Bayview Blvd,Suite 200,Room 05A721, Baltimore, MD 21224 USA. EM mhuestis@intra.nida.nih.gov FU National Institute on Drug Abuse (NIDA), National Institutes of Health; NIDA [RO1 DA12220] FX This research was supported by the Intramural Research Program of the National Institute on Drug Abuse (NIDA), National Institutes of Health, and NIDA grant RO1 DA12220. NR 27 TC 13 Z9 13 U1 0 U2 2 PU PRESTON PUBL INC PI NILES PA 6600 W TOUHY AVE, NILES, IL 60714-4588 USA SN 0146-4760 J9 J ANAL TOXICOL JI J. Anal. Toxicol. PD OCT PY 2010 VL 34 IS 8 SI SI BP 498 EP 505 PG 8 WC Chemistry, Analytical; Toxicology SC Chemistry; Toxicology GA 654SS UT WOS:000282191200010 PM 21819795 ER PT J AU Dauter, Z Jaskolski, M AF Dauter, Zbigniew Jaskolski, Mariusz TI How to read (and understand) Volume A of International Tables for Crystallography: an introduction for nonspecialists SO JOURNAL OF APPLIED CRYSTALLOGRAPHY LA English DT Article DE symmetry; space groups; International Tables for Crystallography; crystallographic education AB Since fewer and fewer students get proper crystallographic education at the undergraduate level, the responsibility to promote and propagate this knowledge must be directed to alternative channels. It is not a marginal issue, because the language of crystallography is rather hermetic and, without proper support, it might disappear from the collective scientific knowledge, so that in the next generation there would be no-one able to use it properly, to say nothing about advancing the field. Black-box crystallography might be useful in some situations, but it cannot replace well informed, conscious scientific pursuits by properly trained specialists. Without sufficient understanding of crystallographic terms and principles, the now thriving branch of structural research would wither, and this could have particularly lamentable consequences for structural biology. The purpose of this article is to teach non-initiated persons, primarily structural biologists, how to interpret the information contained in the fundamental Volume A of International Tables for Crystallography (ITA). An excellent and comprehensive overview of many issues concerning crystal symmetry is presented in a book by Burns & Glazer (Space Groups for Solid State Scientists, 2nd ed. New York: Academic Press, 1990), also explaining the contents of ITA, but this text is unfortunately not popular among structural biologists. There are several superb handbooks explaining the foundations of structural crystallography but they usually do it without direct reference to ITA. There is also a comprehensive introduction included in ITA, but it is written in rather hermetic language and is, therefore, not suitable for nonspecialists with no training in exact sciences. This article, which uses simple language to explain all the terms encountered on the space-group pages of ITA, is meant to bridge this growing gap in crystallographic instruction. The explanations are illustrated with actual examples taken directly from the pages of ITA. C1 [Dauter, Zbigniew] NCI, Synchrotron Radiat Res Sect, Macromol Crystallog Lab, Argonne Natl Lab, Argonne, IL 60439 USA. [Jaskolski, Mariusz] Adam Mickiewicz Univ Poznan, Fac Chem, Dept Crystallog, Poznan, Poland. [Jaskolski, Mariusz] Polish Acad Sci, Inst Bioorgan Chem, Ctr Biocrystallog Res, Poznan, Poland. RP Dauter, Z (reprint author), NCI, Synchrotron Radiat Res Sect, Macromol Crystallog Lab, Argonne Natl Lab, Argonne, IL 60439 USA. EM zdauter@anl.gov; mariuszj@amu.edu.pl NR 8 TC 4 Z9 4 U1 4 U2 31 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0021-8898 J9 J APPL CRYSTALLOGR JI J. Appl. Crystallogr. PD OCT PY 2010 VL 43 BP 1150 EP 1171 DI 10.1107/S0021889810026956 PN 5 PG 22 WC Chemistry, Multidisciplinary; Crystallography SC Chemistry; Crystallography GA 652IU UT WOS:000281998200004 ER PT J AU Zulkifli, L Akai, M Yoshikawa, A Shimojima, M Ohta, H Guy, HR Uozumi, N AF Zulkifli, Lalu Akai, Masaro Yoshikawa, Asuka Shimojima, Mie Ohta, Hiroyuki Guy, H. Robert Uozumi, Nobuyuki TI The KtrA and KtrE Subunits Are Required for Na+-Dependent K+ Uptake by KtrB across the Plasma Membrane in Synechocystis sp. Strain PCC 6803 SO JOURNAL OF BACTERIOLOGY LA English DT Article ID POTASSIUM TRANSPORTER HKT1; UPTAKE SYSTEM KTRAB; VIBRIO-ALGINOLYTICUS; HIGH-AFFINITY; GLYCINE RESIDUES; SP PCC-6803; SELECTIVITY; MUTATIONS; CHANNELS; COMPLEX AB The Na+-dependent K+ uptake KtrABE system is essential for the adaptation of Synechocystis to salinity stress and high osmolality. While KtrB forms the K+-translocating pore, the role of the subunits KtrA and KtrE for Ktr function remains elusive. Here, we characterized the role of KtrA and KtrE in Ktr-mediated K+ uptake and in modulating Na+ dependency. Expression of KtrB alone in a K+ uptake-deficient Escherichia coli strain conferred low K+ uptake activity that was not stimulated by Na+. Coexpression of both KtrA and KtrE with KtrB increased the K+ transport activity in a Na+-dependent manner. KtrA and KtrE were found to be localized to the plasma membrane in Synechocystis. Site-directed mutagenesis was used to analyze the role of single charged residues in KtrB for Ktr function. Replacing negatively charged residues facing the extracellular space with residues of the opposite charge increased the apparent K-m for K+ in all cases. However, none of the mutations eliminated the Na+ dependency of Ktr-mediated K+ transport. Mutations of residues on the cytoplasmic side had larger effects on K+ uptake activity than those of residues on the extracellular side. Further analysis revealed that replacement of R262, which is well conserved among Ktr/Trk/HKT transporters in the third extracellular loop, by Glu abolished transport activity. The atomic-scale homology model indicated that R262 might interact with E247 and D261. Based on these data, interaction of KtrA and KtrE with KtrB increased the K+ uptake rate and conferred Na+ dependency. C1 [Zulkifli, Lalu; Akai, Masaro; Yoshikawa, Asuka; Uozumi, Nobuyuki] Tohoku Univ, Dept Biomol Engn, Grad Sch Engn, Sendai, Miyagi 9808579, Japan. [Shimojima, Mie; Ohta, Hiroyuki] Tokyo Inst Technol, Ctr Biol Resources & Informat, Midori Ku, Yokohama, Kanagawa 2268501, Japan. [Guy, H. Robert] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Uozumi, N (reprint author), Tohoku Univ, Dept Biomol Engn, Grad Sch Engn, Aobayama 6-6-07, Sendai, Miyagi 9808579, Japan. EM uozumi@biophy.che.tohoku.ac.jp RI Shimojima, Mie/B-5880-2015; Ohta, Hiroyuki/B-1840-2014 OI Shimojima, Mie/0000-0003-3172-8638; FU MEXT [17078005, 20-08103, 20246044, 22020002, 22380056]; JSPS; Salt Science Research Foundation FX This work was supported in part by Grants-in-Aid for Scientific Research (17078005, 20-08103, 20246044, 22020002, and 22380056) from MEXT and JSPS and by the Salt Science Research Foundation. NR 39 TC 10 Z9 11 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD OCT PY 2010 VL 192 IS 19 BP 5063 EP 5070 DI 10.1128/JB.00569-10 PG 8 WC Microbiology SC Microbiology GA 650QW UT WOS:000281866900027 PM 20656904 ER PT J AU Moretz, SE Lampson, BC AF Moretz, Samuel E. Lampson, Bert C. TI A Group IIC-Type Intron Interrupts the rRNA Methylase Gene of Geobacillus stearothermophilus Strain 10 SO JOURNAL OF BACTERIOLOGY LA English DT Article ID STEM-LOOP MOTIF; REVERSE TRANSCRIPTASES; RETROELEMENTS; KAUSTOPHILUS; RECOGNITION; TERMINATORS; EUBACTERIA; DIVERSITY; BACTERIA; SEQUENCE AB Group IIC introns insert next to the stem-loop structure of rho-independent transcription terminators, thus avoiding intact genes. The insertion sites of 17 copies of the G.st.I1 intron from Geobacillus stearothermophilus were compared. One copy of the intron was found to interrupt an open reading frame (ORF) encoding an rRNA methylase. C1 [Lampson, Bert C.] E Tennessee State Univ, Dept Hlth Sci, Johnson City, TN 37614 USA. [Moretz, Samuel E.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. RP Lampson, BC (reprint author), E Tennessee State Univ, Dept Hlth Sci, Box 70673, Johnson City, TN 37614 USA. EM Lampson@etsu.edu OI Lampson, Bert/0000-0003-2529-0254 FU College of Public Health, East Tennessee State University; Takara Bio Inc. FX This work was generously supported by a grant from the College of Public Health, East Tennessee State University, and a grant from Takara Bio Inc. (B.C.L.). NR 21 TC 2 Z9 2 U1 0 U2 0 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 OCT PY 2010 VL 192 IS 19 BP 5245 EP 5248 DI 10.1128/JB.00633-10 PG 4 WC Microbiology SC Microbiology GA 650QW UT WOS:000281866900046 PM 20675491 ER PT J AU Someya, A Moss, J Nagaoka, I AF Someya, Akimasa Moss, Joel Nagaoka, Isao TI The Guanine Nucleotide Exchange Protein for ADP-ribosylation Factor 6, ARF-GEP100/BRAG2, Regulates Phagocytosis of Monocytic Phagocytes in an ARF6-dependent Process SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RECEPTOR-MEDIATED PHAGOCYTOSIS; PLASMA-MEMBRANE; ACTIN CYTOSKELETON; ARF6 ACTIVATION; PHOSPHOLIPASE-D; CELL-ADHESION; GROWTH-FACTOR; MACROPHAGES; COMPONENTS; EFFECTOR AB Phagocytosis is a complex multistep process requiring diverse signaling and regulatory molecules. ADP-ribosylation factor 6 (ARF6), a small GTPase, is known to regulate membrane trafficking and the actin cytoskeketon at the plasma membrane and functions as a regulatory molecule of phagocytosis. ARF activity is regulated by cycling between GDP-bound and GTP-bound forms. ARF activation is catalyzed by guanine nucleotide exchange factors (GEFs) that facilitate GTP binding. We had earlier reported a 100-kDa ARF-GEF, termed ARF-guanine nucleotide exchange protein 100, GEP100, that preferentially activates ARF6 and was also described by Dunphy et al. (Dunphy, J. L., Moravec, R., Ly, K., Lasell, T. K., Melancon, P., and Casanova, J. E. (2006) Curr. Biol. 16, 315-320) as brefeldin A-resistant ARF-GEF2 (BRAG2). We have now examined a role for GEP100 in phagocytosis. Stable depletion of GEP100 decreased phagocytosis of serum-treated zymosan and IgG-coated latex beads by human monocyte-macrophage-like U937 cells differentiated with phorbol 12-myristate 13-acetate. Decrease of phagocytic activity by RNAi was not rescued by GEP100 Delta Sec7, a deletion mutant lacking the ARF-activating domain. GEP100-depleted cells also exhibited reduced F-actin fibers around internalized particles. Attachment of these particles to cells and amounts of C3bi and Fc gamma receptors, however, were not affected by GEP100 depletion. On immunofluorescence microscopy, GEP100 and ARF6 were concentrated and partially colocalized around internalized particles. Phagocytosis by GEP100-depleted cells was not further affected by depletion of ARF6. Phagocytic activity of GEP100-depleted cells was, however, rescued by expression of the constitutively active ARF6Q67N mutant but not by the dominant-negative ARF6T27N mutant. These data are consistent with the conclusion that GEP100 functions in phago-cytosis via its role in ARF6-dependent actin remodeling. C1 [Someya, Akimasa] Juntendo Univ, Sch Med, Dept Host Def & Biochem Res, Bunkyo Ku, Tokyo 1138421, Japan. [Moss, Joel] NHLBI, Translat Med Branch, NIH, Bethesda, MD 20892 USA. RP Someya, A (reprint author), Juntendo Univ, Sch Med, Dept Host Def & Biochem Res, Bunkyo Ku, 2-1-1 Hongo, Tokyo 1138421, Japan. EM someya@juntendo.ac.jp FU National Institutes of Health, NHLBI; Ministry of Education, Culture, Sports, Science, and Technology of Japan FX This work was supported, in whole or in part, by the Intramural Research Program, National Institutes of Health, NHLBI. This work was also supported by the "High-Tech Research Center" Project for Private Universities (a matching fund subsidy from the Ministry of Education, Culture, Sports, Science, and Technology of Japan). NR 48 TC 6 Z9 6 U1 1 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 1 PY 2010 VL 285 IS 40 BP 30698 EP 30707 DI 10.1074/jbc.M110.107458 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 653YS UT WOS:000282135500038 PM 20601426 ER EF