FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Aviles, RJ Thompson, RB Ozturk, C Raval, AN DeSilva, R Stine, A Wright, V Raman, VK Balaban, RS Lederman, RJ AF Aviles, RJ Thompson, RB Ozturk, C Raval, AN DeSilva, R Stine, A Wright, V Raman, VK Balaban, RS Lederman, RJ TI Heterogeneous skeletal muscle perfusion recovery after stenting: Insight into regional ischemic blood flow control SO CIRCULATION LA English DT Meeting Abstract CT 78th Annual Scientific Session of the American-Heart-Association CY NOV 13-16, 2005 CL Dallas, TX SP Amer Heart Assoc C1 NHLBI, NIH, Bethesda, MD 20892 USA. Univ Alberta, Edmonton, AB T6G 2M7, Canada. RI Ozturk, Cengizhan/A-6177-2016 OI Ozturk, Cengizhan/0000-0002-6966-0774 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU S MA 1790 BP U417 EP U418 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956402372 ER PT J AU Bensimhon, DR Ellis, SJ Leifer, ES Brawner, CA Whellan, DJ Pina, IL Keteyian, SJ Kraus, WE Fleg, JL O'Connor, CM AF Bensimhon, DR Ellis, SJ Leifer, ES Brawner, CA Whellan, DJ Pina, IL Keteyian, SJ Kraus, WE Fleg, JL O'Connor, CM TI Low heart rate reserve and presence of paced rhythm predict poor exercise tolerance in heart failure patients: Preliminary data from HF-ACTION SO CIRCULATION LA English DT Meeting Abstract CT 78th Annual Scientific Session of the American-Heart-Association CY NOV 13-16, 2005 CL Dallas, TX SP Amer Heart Assoc C1 Duke Univ, Ctr Med, Durham, NC USA. Duke Univ, Clin Res Inst, Durham, NC USA. NHLBI, NIH, Bethesda, MD 20892 USA. Henry Ford Hosp, Detroit, MI 48202 USA. Jefferson Med Coll, Philadelphia, PA 19107 USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU S MA 2800 BP U654 EP U654 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956404104 ER PT J AU Bluemke, DA Kronmal, RA Lima, JA Olson, J Burke, G Folsom, A AF Bluemke, DA Kronmal, RA Lima, JA Olson, J Burke, G Folsom, A TI Incident congestive heart failure in the MESA study: Relationship to left ventricular mass SO CIRCULATION LA English DT Meeting Abstract CT 78th Annual Scientific Session of the American-Heart-Association CY NOV 13-16, 2005 CL Dallas, TX SP Amer Heart Assoc C1 Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Univ Washington, Seattle, WA 98195 USA. NHLBI, Bethesda, MD 20892 USA. Wake Forest Univ Hlth Sci, Winston Salem, NC USA. Univ Minnesota, Div Epidemiol, Minneapolis, MN 55455 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU S MA 3714 BP U866 EP U866 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956406111 ER PT J AU Bray, PF Mathias, RA Herrera-Galeano, JE Yanek, LR Faraday, N Hasan, AA Wilson, AF Becker, LC Becker, DM AF Bray, PF Mathias, RA Herrera-Galeano, JE Yanek, LR Faraday, N Hasan, AA Wilson, AF Becker, LC Becker, DM TI Heritability of platelet reactivity in white and African American subjects at moderately high risk of coronary artery disease SO CIRCULATION LA English DT Meeting Abstract CT 78th Annual Scientific Session of the American-Heart-Association CY NOV 13-16, 2005 CL Dallas, TX SP Amer Heart Assoc C1 Baylor Coll Med, Houston, TX 77030 USA. NHGRI, Baltimore, MD USA. Johns Hopkins Med Inst, Baltimore, MD 21205 USA. NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU S MA 443 BP U128 EP U129 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956400388 ER PT J AU Butler, J Zhu, YW Fazio, S Vaughan, D Figaro, K Goodpaster, B Bauer, D Holvoet, P Harris, T Rekeneire, NC Rubin, S Ding, JZ Rodondi, N Kritchevsky, S AF Butler, J Zhu, YW Fazio, S Vaughan, D Figaro, K Goodpaster, B Bauer, D Holvoet, P Harris, T Rekeneire, NC Rubin, S Ding, JZ Rodondi, N Kritchevsky, S TI Metabolic syndrome predicts adverse cardiovascular risk among the elderly SO CIRCULATION LA English DT Meeting Abstract CT 78th Annual Scientific Session of the American-Heart-Association CY NOV 13-16, 2005 CL Dallas, TX SP Amer Heart Assoc C1 Vanderbilt Univ, Med Ctr, Nashville, TN USA. Univ Tennessee, Memphis, TN 38163 USA. Univ Pittsburgh, Pittsburgh, PA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Catholic Univ Louvain, B-3000 Louvain, Belgium. NIA, NIH, Bethesda, MD 20892 USA. Wake Forest Univ, Winston Salem, NC 27109 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU S MA 3633 BP U847 EP U847 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956406030 ER PT J AU Cao, JJ Biggs, ML Barzilay, J Konen, J Psaty, BM Kuller, L Bleyer, AJ Olson, J Wexler, J Summerson, J Cushman, M AF Cao, JJ Biggs, ML Barzilay, J Konen, J Psaty, BM Kuller, L Bleyer, AJ Olson, J Wexler, J Summerson, J Cushman, M TI Microalbuminuria and the risk of cardiovascular events and all-cause mortality in the elderly, The cardiovascular health study SO CIRCULATION LA English DT Meeting Abstract CT 78th Annual Scientific Session of the American-Heart-Association CY NOV 13-16, 2005 CL Dallas, TX SP Amer Heart Assoc C1 NIH, Bethesda, MD 20892 USA. Univ Washington, Seattle, WA 98195 USA. Emory Univ, Atlanta, GA 30322 USA. Pfizer Inc, Ann Arbor, MI USA. Univ Pittsburgh, Pittsburgh, PA USA. Wake Forest Univ, Winston Salem, NC 27109 USA. Medstar Hlth, Baltimore, MD USA. Univ Vermont, Burlington, VT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU S MA 3632 BP U847 EP U847 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956406029 ER PT J AU Cao, JJ Sigurdsson, S Vincent, P Padmanabhan, S Holly, J Launer, L Aletras, AH Eiriksdottir, G Thorgeirsson, G Aspelund, T Gudnason, V Harris, T Arai, AE AF Cao, JJ Sigurdsson, S Vincent, P Padmanabhan, S Holly, J Launer, L Aletras, AH Eiriksdottir, G Thorgeirsson, G Aspelund, T Gudnason, V Harris, T Arai, AE TI The prevalence of infarct and non-infarct as the etiology in impaired left ventricular systolic function in the elderly: A gadolinium enhanced cardiac MRI study SO CIRCULATION LA English DT Meeting Abstract CT 78th Annual Scientific Session of the American-Heart-Association CY NOV 13-16, 2005 CL Dallas, TX SP Amer Heart Assoc C1 NIH, Bethesda, MD 20892 USA. Iceland Heart Assoc, Reykjavik, Iceland. RI Aspelund, Thor/C-5983-2008; Aspelund, Thor/F-4826-2011; 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 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU S MA 2458 BP U574 EP U574 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956403379 ER PT J AU Chavakis, E Hain, A Bianchi, ME Dimmeler, S AF Chavakis, E Hain, A Bianchi, ME Dimmeler, S TI High mobility group box protein 1 stimulates migration and adhesion of endothelial progenitor cells via integrin-dependent pathways SO CIRCULATION LA English DT Meeting Abstract CT 78th Annual Scientific Session of the American-Heart-Association CY NOV 13-16, 2005 CL Dallas, TX SP Amer Heart Assoc C1 Univ Frankfurt, Med Clin, Frankfurt A M, Germany. San Raffaele Univ, Milan, Italy. NCI, Expt Immunol Branch, 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 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU S MA 1063 BP U261 EP U261 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956401301 ER PT J AU Chesley, A Bind, E Crider, D Boheler, K Crow, MT AF Chesley, A Bind, E Crider, D Boheler, K Crow, MT TI The apoptosis repressor with CARD (ARC) blocks the mitochondrial death pathway in cardiomyocytes by interfering with assembly of the mitochondrial fission complex SO CIRCULATION LA English DT Meeting Abstract CT 78th Annual Scientific Session of the American-Heart-Association CY NOV 13-16, 2005 CL Dallas, TX SP Amer Heart Assoc C1 Johns Hopkins Univ, Sch Med, Baltimore, MD USA. NIA, NIH, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU S MA 1113 BP U271 EP U271 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956401351 ER PT J AU Claudel, T Inoue, Y Duez, H Percevault, F van der Weide, J Gonzalez, FJ Omiecinski, CJ Staels, B Kuipers, F AF Claudel, T Inoue, Y Duez, H Percevault, F van der Weide, J Gonzalez, FJ Omiecinski, CJ Staels, B Kuipers, F TI Constitutive androstane receptor negatively regulates human apolipoprotein A-1 expression SO CIRCULATION LA English DT Meeting Abstract CT 78th Annual Scientific Session of the American-Heart-Association CY NOV 13-16, 2005 CL Dallas, TX SP Amer Heart Assoc C1 UMCG Groningen, Groningen, Netherlands. Natl Canc Inst, Met Lab, Ctr Canc Res, NIH, Bethesda, MD USA. Inst Pasteur, INSERM, UR 545, F-59019 Lille, France. St Jansdal Hosp, Dept Clin Chem, Harderwijk, Netherlands. Penn State Univ, Dept Vet Sci, University Pk, PA 16802 USA. RI Staels, Bart/N-9497-2016 OI Staels, Bart/0000-0002-3784-1503 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU S MA 938 BP U234 EP U234 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956401176 ER PT J AU Cook, NR Cutler, JA Obarzanek, E Buring, JE Rexrode, KM Whelton, PK AF Cook, NR Cutler, JA Obarzanek, E Buring, JE Rexrode, KM Whelton, PK TI Sodium excretion in the trials of hypertension prevention (TOHP) and subsequent cardiovascular disease SO CIRCULATION LA English DT Meeting Abstract CT 78th Annual Scientific Session of the American-Heart-Association CY NOV 13-16, 2005 CL Dallas, TX SP Amer Heart Assoc C1 Brigham & Womens Hosp, Boston, MA 02115 USA. NHLBI, Bethesda, MD 20892 USA. Tulane Univ, New Orleans, LA 70118 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU S MA 3795 BP U895 EP U896 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956406192 ER PT J AU Daviglus, ML Greenland, P Liu, K Psaty, B Arnold, AM Schreiner, P Saad, MF Blumenthal, RS Olson, J Burke, G AF Daviglus, ML Greenland, P Liu, K Psaty, B Arnold, AM Schreiner, P Saad, MF Blumenthal, RS Olson, J Burke, G TI Benefits of favorable risk factor profile (low risk) on subclinical atherosclerosis are found across age, gender, ethnic, and education groups: The multi-ethnic study of atherosclerosis (MESA) SO CIRCULATION LA English DT Meeting Abstract CT 78th Annual Scientific Session of the American-Heart-Association CY NOV 13-16, 2005 CL Dallas, TX SP Amer Heart Assoc C1 Northwestern Univ, Chicago, IL 60611 USA. Univ Washington, Seattle, WA 98195 USA. Univ Minnesota, Minneapolis, MN USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. NHLBI, Bethesda, MD 20892 USA. Wake Forest Univ, Winston Salem, NC 27109 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU S MA 3588 BP U837 EP U837 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956405256 ER PT J AU de Simone, G Gottdiener, JS Chinali, M Marino, EK Maurer, M Manolio, T AF de Simone, G Gottdiener, JS Chinali, M Marino, EK Maurer, M Manolio, T TI Incident congestive heart failure in elderly subjects with inapprorpiate left ventricular mass: The cardiovascular health study SO CIRCULATION LA English DT Meeting Abstract CT 78th Annual Scientific Session of the American-Heart-Association CY NOV 13-16, 2005 CL Dallas, TX SP Amer Heart Assoc C1 Federico II Univ Hosp, Naples, Italy. Univ Maryland, Baltimore, MD 21201 USA. Univ Washington, Washington, DC USA. Columbia Univ, New York, NY 10027 USA. NIH, Bethesda, MD 20892 USA. RI Chinali, Marcello/H-5794-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU S MA 1988 BP U468 EP U468 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956402570 ER PT J AU Doyle, M Pohost, GM Shaw, LJ Sopko, G Kortright, E Vido, DA Kelsey, SF Johnson, BD Rogers, WJ Reis, SE Olson, MB Sharaf, BL Pepine, CJ Mankad, S Biederman, RW AF Doyle, M Pohost, GM Shaw, LJ Sopko, G Kortright, E Vido, DA Kelsey, SF Johnson, BD Rogers, WJ Reis, SE Olson, MB Sharaf, BL Pepine, CJ Mankad, S Biederman, RW TI Internal, not external, ventricular energy utilization measured by MRI, coupled with coronary artery disease, assess risk in women: the NHLBI-sponsored women's ischemia syndrome evaluation (WISE) study SO CIRCULATION LA English DT Meeting Abstract CT 78th Annual Scientific Session of the American-Heart-Association CY NOV 13-16, 2005 CL Dallas, TX SP Amer Heart Assoc C1 Univ So Calif, Los Angeles, CA USA. ACRI, Atlanta, GA USA. NHLBI, NIH, Washington, DC USA. Univ New Orleans, New Orleans, LA 70148 USA. Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. Epidemiol Data Ctr, Pittsburgh, PA USA. Univ Alabama, Birmingham, AL USA. Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. Rhode Isl Hosp, Providence, RI USA. Univ Florida, Gainesville, FL USA. RI Reis, Steven/J-3957-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU S MA 3395 BP U791 EP U791 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956405063 ER PT J AU Drukteinis, JS Fabsitz, RR Best, LG Howard, BV Devereux, R AF Drukteinis, JS Fabsitz, RR Best, LG Howard, BV Devereux, R TI Cardiac and systemic hemodynamic characteristics of hypertension in adolescents and young adults: The strong heart family study SO CIRCULATION LA English DT Meeting Abstract CT 78th Annual Scientific Session of the American-Heart-Association CY NOV 13-16, 2005 CL Dallas, TX SP Amer Heart Assoc C1 Cornell Univ, Weill Med Coll, New York, NY 10021 USA. NHLBI, NIH, DECA, Bethesda, MD 20892 USA. Missour Breaks Ind Res Inc, Timber Lakes, SD USA. MedStar Res Inst, Hyattsville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU S MA 3709 BP U864 EP U865 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956406106 ER PT J AU El-Bizri, N Wang, LL Martinez, EC Urashima, T Mishina, Y Rabinovitch, M AF El-Bizri, N Wang, LL Martinez, EC Urashima, T Mishina, Y Rabinovitch, M TI Vascular defects and embryonic lethality in transgenic mice with endothelial cell-specific deletion of the bone morphogenetic protein type IA receptor (BMPR-IA) SO CIRCULATION LA English DT Meeting Abstract CT 78th Annual Scientific Session of the American-Heart-Association CY NOV 13-16, 2005 CL Dallas, TX SP Amer Heart Assoc C1 Stanford Univ, Palo Alto, CA 94304 USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. RI Martinez, Eliana/A-4782-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU S MA 553 BP U152 EP U152 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956400498 ER PT J AU Fox, CS Coady, S Sorlie, PD D'Agostino, RB Vasan, RS Meigs, JB Levy, D Savage, PJ AF Fox, CS Coady, S Sorlie, PD D'Agostino, RB Vasan, RS Meigs, JB Levy, D Savage, PJ TI Trends in diabetes as a cardiovascular disease risk factor: The Framingham Heart Study SO CIRCULATION LA English DT Meeting Abstract CT 78th Annual Scientific Session of the American-Heart-Association CY NOV 13-16, 2005 CL Dallas, TX SP Amer Heart Assoc C1 NHLBI, Framingham Heart Study, Framingham, MA USA. Boston Univ, Med Ctr, Boston, MA 02215 USA. NHLBI, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU S MA 3674 BP U856 EP U856 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956406071 ER PT J AU Hamburg, NM Larson, MG Vita, JA Meigs, JB Keyes, MJ Widlansky, ME Fox, CS Mitchell, GF Levy, D Vasan, RS Benjamin, EJ AF Hamburg, NM Larson, MG Vita, JA Meigs, JB Keyes, MJ Widlansky, ME Fox, CS Mitchell, GF Levy, D Vasan, RS Benjamin, EJ TI Metabolic syndrome, insulin resistance and brachial artery vasodilator function in the framingham heart study SO CIRCULATION LA English DT Meeting Abstract CT 78th Annual Scientific Session of the American-Heart-Association CY NOV 13-16, 2005 CL Dallas, TX SP Amer Heart Assoc C1 Boston Univ, Sch Med, Boston, MA 02118 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NHLBI Framingham Heart Study, Framingham, MA USA. Cardiovasc Engn Inc, Holliston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU S MA 3616 BP U843 EP U843 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956406013 ER PT J AU Hiroi, Y Kim, HH Cheng, SY Moskowitz, MA Liao, JK AF Hiroi, Y Kim, HH Cheng, SY Moskowitz, MA Liao, JK TI Stroke protection by rapid, non-genomic actions of thyroid hormone SO CIRCULATION LA English DT Meeting Abstract CT 78th Annual Scientific Session of the American-Heart-Association CY NOV 13-16, 2005 CL Dallas, TX SP Amer Heart Assoc C1 Natl Inst Hlth, Bethesda, MD USA. Massachusetts Gen Hosp, Charlestown, MA USA. Brigham Womens HOsp, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU S MA 716 BP U185 EP U185 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956400661 ER PT J AU Iantorno, M Schinzari, F Tesauro, M Rizza, S Melina, D Lauro, D Cardillo, C AF Iantorno, M Schinzari, F Tesauro, M Rizza, S Melina, D Lauro, D Cardillo, C TI Ghrelin improves endothelial function in patients with metabolic syndrome SO CIRCULATION LA English DT Meeting Abstract CT 78th Annual Scientific Session of the American-Heart-Association CY NOV 13-16, 2005 CL Dallas, TX SP Amer Heart Assoc C1 NIH, Bethesda, MD 20892 USA. Catholic Univ Rome, Sch Med, Rome, Italy. Univ Roma Tor Vergata, Sch Med, Rome, Italy. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU S MA 3172 BP U740 EP U741 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956404476 ER PT J AU Iesaki, T Arikawa-Hirasawa, E Nakamura, T Njaman, W Kosaki, K Yamada, Y Daida, H AF Iesaki, T Arikawa-Hirasawa, E Nakamura, T Njaman, W Kosaki, K Yamada, Y Daida, H TI Vascular hypercontraction and endothelial dysfunction in perlecan-null mouse aorta SO CIRCULATION LA English DT Meeting Abstract CT 78th Annual Scientific Session of the American-Heart-Association CY NOV 13-16, 2005 CL Dallas, TX SP Amer Heart Assoc C1 Juntendo Univ, Dept Cardiol, Tokyo, Japan. Juntendo Univ, Dept Neurol, Tokyo, Japan. Juntendo Univ, Dept Physiol, Tokyo, Japan. Natl Inst Dent & Craniofacial Res, CDBRB, 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 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU S MA 1569 BP U366 EP U366 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956402151 ER PT J AU Imahashi, K Steenbergen, C Philipson, KD Murphy, E AF Imahashi, K Steenbergen, C Philipson, KD Murphy, E TI Cardiac-specific ablation of the Na+/Ca2+ exchanger confers protection against ischemia-reperfusion injury SO CIRCULATION LA English DT Meeting Abstract CT 78th Annual Scientific Session of the American-Heart-Association CY NOV 13-16, 2005 CL Dallas, TX SP Amer Heart Assoc C1 Duke Univ, Durham, NC USA. NIEHS, Res Triangle Pk, NC 27709 USA. Univ Calif Los Angeles, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU S MA 1288 BP U309 EP U310 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956401526 ER PT J AU Lee, CR North, KE Bray, MS Fornage, M Seubert, JM Couper, DJ Heiss, G Zeldin, DC AF Lee, CR North, KE Bray, MS Fornage, M Seubert, JM Couper, DJ Heiss, G Zeldin, DC TI Genetic variation in soluble epoxide hydrolase (EPHX2) and risk of coronary heart disease: An atherosclerosis risk in communities (ARIC) study SO CIRCULATION LA English DT Meeting Abstract CT 78th Annual Scientific Session of the American-Heart-Association CY NOV 13-16, 2005 CL Dallas, TX SP Amer Heart Assoc C1 Univ N Carolina, Chapel Hill, NC USA. Baylor Coll Med, Houston, TX 77030 USA. Univ Texas, Hlth Sci Ctr, Houston, TX USA. NIEHS, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU S MA 3801 BP U897 EP U897 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956406198 ER PT J AU Lee, CR North, KE Bray, MS Fornage, M Seubert, JM Couper, DJ Heiss, G Zeldin, DC AF Lee, CR North, KE Bray, MS Fornage, M Seubert, JM Couper, DJ Heiss, G Zeldin, DC TI Genetic variation in soluble epoxide hydrolase (EPHX2) and risk of coronary heart disease: An atherosclerosis risk in communities (ARIC) study SO CIRCULATION LA English DT Meeting Abstract CT 78th Annual Scientific Session of the American-Heart-Association CY NOV 13-16, 2005 CL Dallas, TX SP Amer Heart Assoc C1 Univ N Carolina, Chapel Hill, NC USA. Baylor Coll Med, Houston, TX 77030 USA. Univ Texas, Hlth Sci Ctr, Houston, TX USA. NIEHS, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU S BP U39 EP U39 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956400035 ER PT J AU Liu, LJ Joyce, C Vaisman, B Basso, F Amar, MJ Shamburek, RD Santamarina-Fojo, S AF Liu, LJ Joyce, C Vaisman, B Basso, F Amar, MJ Shamburek, RD Santamarina-Fojo, S TI Contribution of hepatic and extrahepatic ABCA1 to plasma HDL-C and apoB-containing lipoprotein cholesterol in transgenic mice SO CIRCULATION LA English DT Meeting Abstract CT 78th Annual Scientific Session of the American-Heart-Association CY NOV 13-16, 2005 CL Dallas, TX SP Amer Heart Assoc C1 NHLBI, MDB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU S MA 897 BP U226 EP U226 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956401136 ER PT J AU McLeod, CJ McCoy, JP Aziz, A Sack, MN AF McLeod, CJ McCoy, JP Aziz, A Sack, MN TI Inducible mitochondrial uncoupling - An endogenous regulatory mechanism augmenting tolerance to cardiac ischemia SO CIRCULATION LA English DT Meeting Abstract CT 78th Annual Scientific Session of the American-Heart-Association CY NOV 13-16, 2005 CL Dallas, TX SP Amer Heart Assoc C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU S MA 1172 BP U284 EP U284 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956401410 ER PT J AU Melenovsky, V Borlaug, BA Hay, I Rosen, B Corretti, M Ferrucci, L Najjar, SS Kass, DA AF Melenovsky, V Borlaug, BA Hay, I Rosen, B Corretti, M Ferrucci, L Najjar, SS Kass, DA TI Atrial Dilation/Dysfunction: A defining feature of heart failure with normal ejection fraction (HFnEF) SO CIRCULATION LA English DT Meeting Abstract CT 78th Annual Scientific Session of the American-Heart-Association CY NOV 13-16, 2005 CL Dallas, TX SP Amer Heart Assoc C1 Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. NIA, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU S MA 3535 BP U823 EP U823 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956405203 ER PT J AU Merz, CB Johnson, BD Kaizar, EE Stanzyk, F Sharaf, B Bittner, V Berga, SL Braunstein, GD Azziz, R Hodgson, TK Pepine, CJ Kelsey, SF Sopko, G AF Merz, CB Johnson, BD Kaizar, EE Stanzyk, F Sharaf, B Bittner, V Berga, SL Braunstein, GD Azziz, R Hodgson, TK Pepine, CJ Kelsey, SF Sopko, G TI Endogenous androgens and coronary artery disease in women: A report from the NHLBI-sponsored WISE study SO CIRCULATION LA English DT Meeting Abstract CT 78th Annual Scientific Session of the American-Heart-Association CY NOV 13-16, 2005 CL Dallas, TX SP Amer Heart Assoc C1 Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. Univ Pittsburgh, Pittsburgh, PA USA. Univ So Calif, Pittsburgh, PA USA. Univ So Calif, Los Angeles, CA USA. Brown Univ, Providence, RI 02912 USA. Univ Alabama, Birmingham, AL USA. Emory Univ, Atlanta, GA 30322 USA. NHLBI, Bethesda, MD 20892 USA. RI Azziz, Ricardo/N-7229-2014 OI Azziz, Ricardo/0000-0002-3917-0483 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU S MA 2964 BP U690 EP U690 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956404268 ER PT J AU Mitchell, GF DeStefano, AL Larson, MG Benjamin, EJ Chen, MH Ramachandran, VS Vita, JA Levy, D AF Mitchell, GF DeStefano, AL Larson, MG Benjamin, EJ Chen, MH Ramachandran, VS Vita, JA Levy, D TI Heritability and a genome-wide linkage scan for arterial stiffness, wave reflection and mean arterial pressure: The Framingham study SO CIRCULATION LA English DT Meeting Abstract CT 78th Annual Scientific Session of the American-Heart-Association CY NOV 13-16, 2005 CL Dallas, TX SP Amer Heart Assoc C1 Cardiovasc Engn Inc, Waltham, MA USA. Boston Univ, Sch Publ Hlth, Boston, MA USA. Boston Univ, Sch Med, Boston, MA USA. NHLBI Framingham Heart Study, Framingham, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU S MA 3640 BP U849 EP U849 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956406037 ER PT J AU Najjar, SS Gerstenblith, G Shetty, V Morrell, CH Schulman, SP Becker, LC Ferrucci, L Lakatta, EG Fleg, JL AF Najjar, SS Gerstenblith, G Shetty, V Morrell, CH Schulman, SP Becker, LC Ferrucci, L Lakatta, EG Fleg, JL TI The prognostic significance of exercise-induced myocardial ischemia or its absence in asymptomatic volunteers: The Baltimore longitudinal study of aging SO CIRCULATION LA English DT Meeting Abstract CT 78th Annual Scientific Session of the American-Heart-Association CY NOV 13-16, 2005 CL Dallas, TX SP Amer Heart Assoc C1 Johns Hopkins Univ, Baltimore, MD USA. Natl Inst Aging, Baltimore, MD USA. Natl Heart Lung & Blood Inst, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU S MA 3046 BP U709 EP U709 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956404350 ER PT J AU Neufeld, EB O'Brien, KG Demosky, SJ Stonik, JA Sabol, SL Malide, D Combs, CA Remaley, AT Santamarina-Fojo, S Brewer, HB AF Neufeld, EB O'Brien, KG Demosky, SJ Stonik, JA Sabol, SL Malide, D Combs, CA Remaley, AT Santamarina-Fojo, S Brewer, HB TI ABCG1-modifed plasma membrane lipid domains mediate cellular cholesterol efflux to HDL SO CIRCULATION LA English DT Meeting Abstract CT 78th Annual Scientific Session of the American-Heart-Association CY NOV 13-16, 2005 CL Dallas, TX SP Amer Heart Assoc C1 NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU S MA 587 BP U158 EP U158 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956400532 ER PT J AU Oparil, S Davis, B Nwachuku, C Pressel, S AF Oparil, S Davis, B Nwachuku, C Pressel, S TI Stroke results in the antihypertensive and lipid lowering treatment to prevent heart attack trial SO CIRCULATION LA English DT Meeting Abstract CT 78th Annual Scientific Session of the American-Heart-Association CY NOV 13-16, 2005 CL Dallas, TX SP Amer Heart Assoc C1 Univ Alabama, Birmingham, AL USA. Univ Texas, Sch Publ Hlth, Houston, TX USA. NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU S MA 2018 BP U475 EP U475 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956402600 ER PT J AU Owens, DS Arena, RA Smith, K Mohiddin, SA McAreavey, D Bacharach, SL Ulisney, KL Fananapazir, L Hadi, M Plehn, JF AF Owens, DS Arena, RA Smith, K Mohiddin, SA McAreavey, D Bacharach, SL Ulisney, KL Fananapazir, L Hadi, M Plehn, JF TI Indices of ventricular relaxation are not related to objective measures of exercise capacity in non-obstructive hypertrophic cardiomyopathy SO CIRCULATION LA English DT Meeting Abstract CT 78th Annual Scientific Session of the American-Heart-Association CY NOV 13-16, 2005 CL Dallas, TX SP Amer Heart Assoc C1 NHLBI, NIH, Cardiovasc Branch, Bethesda, MD 20892 USA. Virginia Commonwealth Univ Med Coll Virginia, Richmond, VA 23298 USA. NIH, Ctr Clin, Bethesda, MD 20892 USA. RI Arena, Ross/A-3141-2008 OI Arena, Ross/0000-0002-6675-1996 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU S MA 2852 BP U665 EP U665 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956404156 ER PT J AU Padmanabhan, S Shizukuda, Y Aletras, AH Mordini, F Ingkanisorn, WP Cao, J Tripodi, D Rosing, DR Bolan, CD Leitman, SF Arai, AE AF Padmanabhan, S Shizukuda, Y Aletras, AH Mordini, F Ingkanisorn, WP Cao, J Tripodi, D Rosing, DR Bolan, CD Leitman, SF Arai, AE TI Myocardial iron is not significantly abnormal in patients with minimally symptomatic hereditary hemochromatosis SO CIRCULATION LA English DT Meeting Abstract CT 78th Annual Scientific Session of the American-Heart-Association CY NOV 13-16, 2005 CL Dallas, TX SP Amer Heart Assoc C1 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 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU S MA 3401 BP U794 EP U794 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956405078 ER PT J AU Park, SW Kuller, L Kanaya, A Shorr, R Nathalie, DR Harris, T Newman, A AF Park, SW Kuller, L Kanaya, A Shorr, R Nathalie, DR Harris, T Newman, A TI Diabetes mellitus is not a CHO risk equivalent in older adults aged 70 to 79 years SO CIRCULATION LA English DT Meeting Abstract CT 78th Annual Scientific Session of the American-Heart-Association CY NOV 13-16, 2005 CL Dallas, TX SP Amer Heart Assoc C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Pittsburgh, Pittsburgh, PA USA. Univ Tennessee, Memphis, TN USA. NIA, Bethesda, MD 20892 USA. RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU S MA 3665 BP U854 EP U854 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956406062 ER PT J AU Raghahavachari, N Villagra, J Harris, A Logun, C Xu, X Munson, P Kato, G Solomon, MA Danner, RA Gladwin, MT AF Raghahavachari, N Villagra, J Harris, A Logun, C Xu, X Munson, P Kato, G Solomon, MA Danner, RA Gladwin, MT TI Amplified profiling of platelet transcriptome in sickle cell disease reveals global activation and dysregulated arginine processing SO CIRCULATION LA English DT Meeting Abstract CT 78th Annual Scientific Session of the American-Heart-Association CY NOV 13-16, 2005 CL Dallas, TX SP Amer Heart Assoc C1 NIH, CCMD, Bethesda, MD 20892 USA. NIH, CIT, Bethesda, MD 20892 USA. NHLBI, CCMD, NIH, Bethesda, MD 20892 USA. RI Kato, Gregory/I-7615-2014 OI Kato, Gregory/0000-0003-4465-3217 NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU S MA 441 BP U128 EP U128 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956400386 ER PT J AU Raghavachari, N Khan, SS Elshal, M Barb, J Logun, C Munson, PJ Gladwin, MT McCoy, JP Danner, RL Solomon, MA AF Raghavachari, N Khan, SS Elshal, M Barb, J Logun, C Munson, PJ Gladwin, MT McCoy, JP Danner, RL Solomon, MA TI Transcript profiling of peripheral blood circulating endothelial cells SO CIRCULATION LA English DT Meeting Abstract CT 78th Annual Scientific Session of the American-Heart-Association CY NOV 13-16, 2005 CL Dallas, TX SP Amer Heart Assoc C1 NIH, CCMD, Bethesda, MD 20892 USA. NHLBI, NIH, Bethesda, MD 20892 USA. NIH, CIT, Bethesda, MD 20892 USA. NIH, CCMD, NHLBI, Bethesda, MD 20892 USA. RI Elshal, Mohamed/H-7953-2012 NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU S MA 1134 BP U275 EP U276 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956401372 ER PT J AU Rodrigo, ME Benjamin, M Carlow, A Annavajjhala, V Dejam, A Paul, JD Powell, TM Thompson, M McCoy, JP Zalos, G Murphy, M Hill, JM Gladwin, M Orlic, D Cannon, RO AF Rodrigo, ME Benjamin, M Carlow, A Annavajjhala, V Dejam, A Paul, JD Powell, TM Thompson, M McCoy, JP Zalos, G Murphy, M Hill, JM Gladwin, M Orlic, D Cannon, RO TI Contribution of nitric oxide to endothelial progenitor cell mobilization, survival and differentiation potential in patients with coronary artery disease undergoing cardiac rehabilitation SO CIRCULATION LA English DT Meeting Abstract CT 78th Annual Scientific Session of the American-Heart-Association CY NOV 13-16, 2005 CL Dallas, TX SP Amer Heart Assoc C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU S MA 3754 BP U886 EP U886 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956406151 ER PT J AU Roman, MJ Kizer, JR Ali, T Lee, ET Galloway, JM Fabsitz, RR Henderson, JA Howard, BV AF Roman, MJ Kizer, JR Ali, T Lee, ET Galloway, JM Fabsitz, RR Henderson, JA Howard, BV TI Central blood pressure better predicts cardiovascular events than does peripheral blood pressure: The strong heart study SO CIRCULATION LA English DT Meeting Abstract CT 78th Annual Scientific Session of the American-Heart-Association CY NOV 13-16, 2005 CL Dallas, TX SP Amer Heart Assoc C1 Cornell Univ, Weill Med Ctr, New York, NY 10021 USA. Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. Univ Arizona, Tucson, AZ USA. NHLBI, Bethesda, MD 20892 USA. Black Hills Ctr Amer Indian Hlth, Rapid City, SD USA. MedStar Res Inst, 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 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU S MA 3621 BP U844 EP U844 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956406018 ER PT J AU Russo, AM Poole, JE Anderson, J Hellkamp, A Boineau, R Domanski, M Mark, DB Lee, KL Bardy, GH AF Russo, AM Poole, JE Anderson, J Hellkamp, A Boineau, R Domanski, M Mark, DB Lee, KL Bardy, GH TI The sudden cardiac death in heart failure trial: Are there differences between men and women? SO CIRCULATION LA English DT Meeting Abstract CT 78th Annual Scientific Session of the American-Heart-Association CY NOV 13-16, 2005 CL Dallas, TX SP Amer Heart Assoc C1 Univ Penn, Philadelphia, PA 19104 USA. Univ Washington, Seattle, WA 98195 USA. Seattle Inst Cardiac Res, Seattle, WA USA. Duke Univ, Durham, NC USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU S MA 2524 BP U592 EP U592 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956403445 ER PT J AU Ruttmann, E Brant, LJ Concin, H Diem, G Rapp, K Weiland, SK Ulmer, H AF Ruttmann, E Brant, LJ Concin, H Diem, G Rapp, K Weiland, SK Ulmer, H TI Gamma-glutamyl transferase and the risk for fatal cardio- and cerebrovascular events in a cohort of 163,944 Austrian men and women SO CIRCULATION LA English DT Meeting Abstract CT 78th Annual Scientific Session of the American-Heart-Association CY NOV 13-16, 2005 CL Dallas, TX SP Amer Heart Assoc C1 Innsbruck Med Univ, Dept Cardiac Surg, Innsbruck, Austria. NIA, Ctr Gerontol Res, Baltimore, MD 21224 USA. Agcy Prevent & Social Med, Bregenz, Austria. Univ Ulm, Dept Epidemiol, D-89069 Ulm, Germany. Innsbruck Med Univ, Dept Med Stat Informat & Hlth Econ, Innsbruck, Austria. RI Ruttmann, Elfriede/D-6501-2011; vhmpp, aks/F-9756-2012; Ulmer, Hanno/C-3488-2011 OI Ulmer, Hanno/0000-0001-5911-1002 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU S MA 3726 BP U868 EP U868 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956406123 ER PT J AU Schulz, C Konrad, I Bueltmann, A Rudellus, M Ungerer, M Massberg, S AF Schulz, C Konrad, I Bueltmann, A Rudellus, M Ungerer, M Massberg, S TI Glycoprotein VI mediates platelet adhesion to endothelial cells in vivo SO CIRCULATION LA English DT Meeting Abstract CT 78th Annual Scientific Session of the American-Heart-Association CY NOV 13-16, 2005 CL Dallas, TX SP Amer Heart Assoc C1 Tech Univ Munich, D-8000 Munich, Germany. Procorde GmbH, Munich, Germany. NCI, Canc Res Ctr, Bethesda, MD 20892 USA. Univ Tubingen, Tubingen, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU S MA 309 BP U93 EP U93 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956400255 ER PT J AU Segal, JB Herrera-Galeano, JE Faraday, N Yanek, LR Moy, TF Hasan, AA Bray, PF Becker, LC Becker, DM AF Segal, JB Herrera-Galeano, JE Faraday, N Yanek, LR Moy, TF Hasan, AA Bray, PF Becker, LC Becker, DM TI Platelet responsiveness to aspirin differs by sex in families with a history of premature coronary artery disease SO CIRCULATION LA English DT Meeting Abstract CT 78th Annual Scientific Session of the American-Heart-Association CY NOV 13-16, 2005 CL Dallas, TX SP Amer Heart Assoc C1 NHLBI, Bethesda, MD 20892 USA. Baylor Coll Med, Houston, TX 77030 USA. Johns Hopkins Med Inst, Baltimore, MD 21205 USA. RI Segal, Jodi/A-2863-2009 OI Segal, Jodi/0000-0003-3978-9662 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU S MA 3771 BP U890 EP U890 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956406168 ER PT J AU Shaw, L Johnson, BD Cooper-DeHoff, R Bittner, V Kelsey, S Reis, S Sopko, G Pepine, C Sharaf, B Merz, NB AF Shaw, L Johnson, BD Cooper-DeHoff, R Bittner, V Kelsey, S Reis, S Sopko, G Pepine, C Sharaf, B Merz, NB TI Importance of socioeconomic status as a predictor of cardiovascular outcome in women SO CIRCULATION LA English DT Meeting Abstract CT 78th Annual Scientific Session of the American-Heart-Association CY NOV 13-16, 2005 CL Dallas, TX SP Amer Heart Assoc C1 Cedars Sinai Med Ctr, W Hollywood, CA USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. Univ Florida, Gainesville, FL USA. Univ Alabama, Birmingham, AL USA. Univ Pittsburgh, Pittsburgh, PA USA. NHLBI, NIH, Bethesda, MD 20892 USA. Cedars Sinai Med Ctr, W Hollywood, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU S MA 3746 BP U884 EP U884 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956406143 ER PT J AU Sirenko, SG Crider, DG Boheler, KR Stern, MD Lakatta, EG Maltsev, VA AF Sirenko, SG Crider, DG Boheler, KR Stern, MD Lakatta, EG Maltsev, VA TI Cardionnyocytes derived from mouse embryonic stem cells express multiple types developmentally regulated local Ca2+ releases SO CIRCULATION LA English DT Meeting Abstract CT 78th Annual Scientific Session of the American-Heart-Association CY NOV 13-16, 2005 CL Dallas, TX SP Amer Heart Assoc C1 NIA, IRP, NAH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU S MA 173 BP U65 EP U65 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956400119 ER PT J AU Stein, JH Wu, JW Aberg, JA McGovern, ME Deeg, MA Shriver, SL Alston, BL Greenwald, M Lee, D Dube, MP AF Stein, JH Wu, JW Aberg, JA McGovern, ME Deeg, MA Shriver, SL Alston, BL Greenwald, M Lee, D Dube, MP TI Safety and efficacy of extended-release niacin for the treatment of dyslipidemia in patients with human immunodeficiency virus infection: A multicenter study (AIDS clinical trials group study A5148) SO CIRCULATION LA English DT Meeting Abstract CT 78th Annual Scientific Session of the American-Heart-Association CY NOV 13-16, 2005 CL Dallas, TX SP Amer Heart Assoc C1 Univ Wisconsin, Sch Med, Madison, WI USA. Harvard Univ, Boston, MA 02115 USA. CUNY, New York, NY 10021 USA. Kos Pharmaceut, Weston, FL USA. Indiana Univ, Indianapolis, IN 46204 USA. Social & Sci Syst Inc, Silver Spring, MD USA. NIH, Bethesda, MD 20892 USA. Univ Calif San Diego, San Diego, CA 92103 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU S MA 3787 BP U894 EP U894 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956406184 ER PT J AU Sun, JH Picht, E Bers, D Steenbergen, C Murphy, E AF Sun, JH Picht, E Bers, D Steenbergen, C Murphy, E TI S-nitrosylation of the L-type Ca2+ channel is involved in cardioprotection in female hearts SO CIRCULATION LA English DT Meeting Abstract CT 78th Annual Scientific Session of the American-Heart-Association CY NOV 13-16, 2005 CL Dallas, TX SP Amer Heart Assoc C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. Loyola Univ, Dept Physiol, Stritch Sch Med, Maywood, IL 60153 USA. Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. RI Bers, Donald/C-4507-2012 NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU S MA 649 BP U171 EP U171 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956400594 ER PT J AU Taylor, J Fox, E Taylor, H Han, H Arnett, D Myerson, M AF Taylor, J Fox, E Taylor, H Han, H Arnett, D Myerson, M TI Left ventricular geometric patterns in African-Americans: Clinical correlates and influences on systolic and diastolic dysfunction SO CIRCULATION LA English DT Meeting Abstract CT 78th Annual Scientific Session of the American-Heart-Association CY NOV 13-16, 2005 CL Dallas, TX SP Amer Heart Assoc C1 Univ Mississippi, Ctr Med, Jackson, MS 39216 USA. Jackson Heart Study, Jackson, MS USA. Univ Alabama, Birmingham, AL USA. NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU S MA 3595 BP U838 EP U839 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956405263 ER PT J AU Thakore, AH Guo, CY Larson, MG Corey, D Wang, TJ Vasan, RS D'Agostino, RB Lipinska, I Keaney, JF Benjamin, EJ O'Donnell, CJ AF Thakore, AH Guo, CY Larson, MG Corey, D Wang, TJ Vasan, RS D'Agostino, RB Lipinska, I Keaney, JF Benjamin, EJ O'Donnell, CJ TI Association of multiple inflammatory markers with carotid intimal medial thickness and stenosis: The Framingham heart study SO CIRCULATION LA English DT Meeting Abstract CT 78th Annual Scientific Session of the American-Heart-Association CY NOV 13-16, 2005 CL Dallas, TX SP Amer Heart Assoc C1 Boston Med Ctr, Boston, MA USA. NHLBI, Framingham Heart Study, Framingham, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU S MA 607 BP U162 EP U162 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956400552 ER PT J AU Thompson, M Rodrigo, ME Benjamin, M Carlow, A Powell, TM Paul, JD McCoy, JP Zalos, G Orlic, D Hill, JM Cannon, RO AF Thompson, M Rodrigo, ME Benjamin, M Carlow, A Powell, TM Paul, JD McCoy, JP Zalos, G Orlic, D Hill, JM Cannon, RO TI Endothelial progenitor cell mobilization during cardiac rehabilitation: Need for continued exercise after completion of program SO CIRCULATION LA English DT Meeting Abstract CT 78th Annual Scientific Session of the American-Heart-Association CY NOV 13-16, 2005 CL Dallas, TX SP Amer Heart Assoc C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU S MA 3753 BP U886 EP U886 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956406150 ER PT J AU Tocchetti, CG Wang, W Valdivia, HH Aon, MA Katori, T Zaccolo, M O'Rourke, B Froehlich, JP Cheng, HP Paolocci, N AF Tocchetti, CG Wang, W Valdivia, HH Aon, MA Katori, T Zaccolo, M O'Rourke, B Froehlich, JP Cheng, HP Paolocci, N TI Nitroxyl anion: A novel thiol-sensitive positive inotrope that enhances SR Ca2+ release and uptake in cardiomyocytes SO CIRCULATION LA English DT Meeting Abstract CT 78th Annual Scientific Session of the American-Heart-Association CY NOV 13-16, 2005 CL Dallas, TX SP Amer Heart Assoc C1 Johns Hopkins Univ, Baltimore, MD 21218 USA. NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. Univ Wisconsin, Sch Med, Dept Physiol, Madison, WI 53706 USA. Dulbecco Telethon Inst, I-20127 Padua, Italy. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. RI Zaccolo, Manuela/B-3802-2011 NR 0 TC 3 Z9 4 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU 2 MA 1553 BP U363 EP U363 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956402135 ER PT J AU Wang, MY Zhao, D Spinetti, G Zhang, J Jiang, LQ Pintus, G Monticone, RE Lakatta, EG AF Wang, MY Zhao, D Spinetti, G Zhang, J Jiang, LQ Pintus, G Monticone, RE Lakatta, EG TI MMP2 activates TGF-beta 1 and augments T beta RII signaling within the aged arterial wall: Relevance to matrix deposition with aging SO CIRCULATION LA English DT Meeting Abstract CT 78th Annual Scientific Session of the American-Heart-Association CY NOV 13-16, 2005 CL Dallas, TX SP Amer Heart Assoc C1 NIA, NIH, Baltimore, MD 21224 USA. RI Pintus, Gianfranco /C-2975-2009 NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU S MA 623 BP U165 EP U166 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956400568 ER PT J AU White, LW Yanek, LR Yoho, AC Moy, TF Hasan, AA Faraday, N Becker, DM AF White, LW Yanek, LR Yoho, AC Moy, TF Hasan, AA Faraday, N Becker, DM TI Adherence to low dose daily aspirin therapy in families with a history of premature coronary disease SO CIRCULATION LA English DT Meeting Abstract CT 78th Annual Scientific Session of the American-Heart-Association CY NOV 13-16, 2005 CL Dallas, TX SP Amer Heart Assoc C1 Johns Hopkins Med Inst, Baltimore, MD 21205 USA. NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU S MA 2062 BP U485 EP U485 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956402644 ER PT J AU Xiao, BL Jiang, MT Yang, DM Obayashi, M Sutherland, C Walsh, M Ter Keurs, H Chang, HP Chen, W AF Xiao, BL Jiang, MT Yang, DM Obayashi, M Sutherland, C Walsh, M Ter Keurs, H Chang, HP Chen, W TI Characterization of a novel PKA site, Ser-2030, and a multiple protein kinase phosophorylation site, Ser-2808, reveals no PKA hyperphosphorylation of RyR2 in heart failure SO CIRCULATION LA English DT Meeting Abstract CT 78th Annual Scientific Session of the American-Heart-Association CY NOV 13-16, 2005 CL Dallas, TX SP Amer Heart Assoc C1 Univ Calgary, Calgary, AB, Canada. Med Coll Wisconsin, Milwaukee, WI 53226 USA. NIH, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU S MA 448 BP U130 EP U130 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956400393 ER PT J AU Xu, JQS Howard, BV Begum, M Mattil, C Fabsitz, RR Lee, ET AF Xu, JQS Howard, BV Begum, M Mattil, C Fabsitz, RR Lee, ET TI Dietary intake and glylcemic control in a population based sample of American Indian men and women with diabetes: The strong heart study SO CIRCULATION LA English DT Meeting Abstract CT 78th Annual Scientific Session of the American-Heart-Association CY NOV 13-16, 2005 CL Dallas, TX SP Amer Heart Assoc C1 Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. Medstar Res Inst, Hyattsville, MD USA. NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU S MA 3635 BP U848 EP U848 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956406032 ER PT J AU Yar, O Mordini, F Calloway, NH Pinnow, EE Wolf, W Raya, V Fuisz, AR AF Yar, O Mordini, F Calloway, NH Pinnow, EE Wolf, W Raya, V Fuisz, AR TI The prognostic value of stress perfusion cardiac MRI SO CIRCULATION LA English DT Meeting Abstract CT 78th Annual Scientific Session of the American-Heart-Association CY NOV 13-16, 2005 CL Dallas, TX SP Amer Heart Assoc C1 Washington Hosp Ctr, Washington, DC 20010 USA. NIH, Bethesda, MD 20892 USA. Georgetown Univ Hosp, Washington, DC 20007 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU S MA 2457 BP U574 EP U574 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956403378 ER PT J AU Yoshimitsu, M Siatskas, C Liang, SB Rasaiah, VI Poeppl, AG Higuchi, K Ramsubir, S Takenaka, T Murray, GJ Tei, C Brady, RO Medin, JA AF Yoshimitsu, M Siatskas, C Liang, SB Rasaiah, VI Poeppl, AG Higuchi, K Ramsubir, S Takenaka, T Murray, GJ Tei, C Brady, RO Medin, JA TI Long-term and sustained correction in hearts of Fabry mice receiving lentivirally transduced hematopoietic stem/progenitor cells SO CIRCULATION LA English DT Meeting Abstract CT 78th Annual Scientific Session of the American-Heart-Association CY NOV 13-16, 2005 CL Dallas, TX SP Amer Heart Assoc C1 Kagoshima Univ, Dept Cardiovasc Resp & Metab Med, Kagoshima 890, Japan. Univ Toronto, Hlth Network, Ontario Canc Inst, Toronto, ON, Canada. NINDS, Dev & Metab Neurol Branch, 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 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU S MA 147 BP U59 EP U59 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956400093 ER PT J AU Zernecke, A Liehn, EA Gao, JL Kuziel, WA Murphy, PM Weber, C AF Zernecke, A Liehn, EA Gao, JL Kuziel, WA Murphy, PM Weber, C TI Deficiency in CCR5 but not CCR1 protects against neointima formation in apolipoprotein E-deficient mice SO CIRCULATION LA English DT Meeting Abstract CT 78th Annual Scientific Session of the American-Heart-Association CY NOV 13-16, 2005 CL Dallas, TX SP Amer Heart Assoc C1 Univ Hosp Aachen, Dept Mol Cardiovasc Rsch, Aachen, Germany. NIAID, Lab Mol Immunol, Bethesda, MD 20892 USA. Prot Design Labs, Fremont, CA USA. RI Liehn, Elisa/D-9623-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU S MA 437 BP U127 EP U127 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956400382 ER PT J AU Zhu, WZ Yang, DM Crow, MT Xiao, RP AF Zhu, WZ Yang, DM Crow, MT Xiao, RP TI Activation of CaMKII at mitochondria triggers apoptotic cardiomyocyte death SO CIRCULATION LA English DT Meeting Abstract CT 78th Annual Scientific Session of the American-Heart-Association CY NOV 13-16, 2005 CL Dallas, TX SP Amer Heart Assoc C1 Johns Hopkins Univ, Baltimore, MD 21218 USA. NIA, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU S MA 1437 BP U338 EP U338 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956402020 ER PT J AU Zhu, WZ Zhang, SJ Koch, WJ Xiao, RP AF Zhu, WZ Zhang, SJ Koch, WJ Xiao, RP TI beta ARK1 directs beta 2-adrenergic receptor to Gi signaling SO CIRCULATION LA English DT Meeting Abstract CT 78th Annual Scientific Session of the American-Heart-Association CY NOV 13-16, 2005 CL Dallas, TX SP Amer Heart Assoc C1 NIA, Baltimore, MD 21224 USA. Thomas Jefferson Univ, Philadelphia, PA 19107 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU S MA 121 BP U53 EP U54 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956400067 ER PT J AU Zieman, SJ Gerstenblith, G Schulman, SP Najjar, SS Cosgriff, R Townsend, SM Capriotti, A Fleg, JL Lakatta, EG AF Zieman, SJ Gerstenblith, G Schulman, SP Najjar, SS Cosgriff, R Townsend, SM Capriotti, A Fleg, JL Lakatta, EG TI Maximum exercise capacity depends on total arterial systemic compliance and both are improved by L-arginine SO CIRCULATION LA English DT Meeting Abstract CT 78th Annual Scientific Session of the American-Heart-Association CY NOV 13-16, 2005 CL Dallas, TX SP Amer Heart Assoc C1 Johns Hopkins Med Inst, Baltimore, MD 21205 USA. NIA, Ctr Gerontol Res, NIH, Baltimore, MD 21224 USA. NHLBI, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU S MA 2178 BP U511 EP U511 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956403100 ER PT J AU Nishigaki, K Hanson, C Jelacic, T Thompson, D Ruscetti, S AF Nishigaki, K Hanson, C Jelacic, T Thompson, D Ruscetti, S TI Friend spleen focus-forming virus transforms rodent fibroblasts in cooperation with a short form of the receptor tyrosine kinase Stk SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE fibroblast transformation; retroviral envelope protein ID JAAGSIEKTE SHEEP RETROVIRUS; TRUNCATED FORM; ENVELOPE GLYCOPROTEIN; CELL-LINE; ERYTHROLEUKEMIA; PROTEINS; MUTATIONS; ENCODES; GENE AB Friend spleen focus-forming virus (SFFV) causes rapid erythroleukemia in mice due to expression of its unique envelope glycoprotein, gp55. Erythroid cells expressing SFFV gp55 proliferate in the absence of their normal regulator erythropoietin (Epo) because of constitutive activation of Epo signal transduction pathways. Although SFFV infects many cell types, deregulation of cell growth occurs only when SFFV infects erythroid cells, suggesting that these cells express unique proteins that the virus requires to mediate its biological effects. Not only do erythroid cells express the Epo receptor (EpoR), but those from mice susceptible to SFFV-induced erythroleukemia also express a short form of the receptor tyrosine kinase Stk (sf-Stk). In erythroid cells, SFFV gp55 interacts with the EpoR complex and sf-Stk, leading to activation of the kinase and constitutive activation of signal transducing molecules. In this study, we demonstrate that SFFV gp55 can also deregulate the growth of nonerythroid cells when it is coexpressed with sf-Stk. Expression of SFFV gp55 in rodent fibroblasts engineered to express sf-Stk induced their transformation, as demonstrated by focus formation and anchorage-independent growth in vitro. This transformation by SFFV gp55 requires the kinase activity of sf-Stk and the presence of its extracellular domain but not expression of the EpoR or the tyrosine kinase Jak2, which is required for activation of signal transduction pathways through the EpoR. Thus, expression of SFFV gp55 in nonerythroid cells coexpressing sf-Stk results in their uncontrolled growth, demonstrating a previously unrecognized mechanism for retrovirus transformation of rodent fibroblasts and providing insight into SFFV-induced disease. C1 NCI, Lab Canc Prevent, Frederick, MD 21702 USA. RP Ruscetti, S (reprint author), NCI, Lab Canc Prevent, Bldg 469,Room 205, Frederick, MD 21702 USA. EM ruscetti@ncifcrf.gov NR 25 TC 16 Z9 17 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 25 PY 2005 VL 102 IS 43 BP 15488 EP 15493 DI 10.1073/pnas.0506570102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 979GC UT WOS:000232929400041 PM 16223879 ER PT J AU Wu, TH Chen, J Murphy, TF Green, BA Gu, XX AF Wu, TH Chen, J Murphy, TF Green, BA Gu, XX TI Investigation of nontypeable Haemophilus influenzae outer membrane protein P6 as a new carrier for lipooligosaccharide conjugate vaccines SO VACCINE LA English DT Article DE P6; carrier; LOS; conjugate vaccine; nontypeable Haemophilus influenzae ID OUTER-MEMBRANE PROTEIN; TETANUS TOXOID CONJUGATE; OTITIS-MEDIA; HEMOPHILUS-INFLUENZAE; DETOXIFIED LIPOOLIGOSACCHARIDE; INTRANASAL IMMUNIZATION; CAPSULAR POLYSACCHARIDE; ANTIBODY-RESPONSE; IMMUNE-RESPONSES; IMMUNOLOGICAL PROPERTIES AB Nontypeable Haemophilus influenzae (NTHi) outer membrane protein P6 was used as a new protein carrier for NTHi detoxified lipooligosaccharide (dLOS) conjugates due to its conservation and potential to elicit bactericidal antibodies. P6 was covalently conjugated to dLOS of strain 9274 through adipic acid dihydrazide with different ratios of dLOS to P6, which resulted in two conjugate formulations with weight ratios of dLOS to P6 of 3.7 for dLOS-P6 (I) and 1.6 for dLOS-P6 (II). Binding activity of the conjugates was examined by an enzyme-linked immunosorbent assay with mouse monoclonal antibodies specific to LOS and P6 and a rabbit anti-P6 serum. The results showed that the conjugates bound not only to the LOS antibody but also to both P6 antibodies, suggesting that the conjugates retained epitopes of both LOS and P6 antigens. Animal studies revealed that dLOS-P6 (II) induced high levels of anti-LOS and anti-P6 IgGs in mice and rabbits. However, dLOS-P6 (I) induced lower levels of anti-LOS IgGs in mice and rabbits and anti-P6 IgGs in rabbits with no anti-P6 IgGs in mice. In addition, all rabbit, but not mouse, antisera elicited by the conjugates showed bactericidal activity against the homologous strain, and two of them elicited by each conjugate plus Ribi adjuvant showed cross-bactericidal activity against three of five major serotype stains. These data indicate that P6 could serve as an effective carrier for dLOS or other carbohydrate conjugates and that the ratio of carbohydrate to P6 might contribute to immune responses in vivo. Published by Elsevier Ltd. C1 Natl Inst Deafness & Other Commun Disorders, Vaccine Res Sect, Rockville, MD USA. Johns Hopkins Sch Med, Wilmer Eye Inst, Baltimore, MD USA. SUNY Buffalo, Div Infect Dis, Buffalo, NY 14260 USA. Wyeth Vaccines, Pearl River, NY USA. RP Gu, XX (reprint author), Natl Inst Deafness & Other Commun Disorders, Vaccine Res Sect, Rockville, MD USA. EM guxx@nidcd.nih.gov NR 43 TC 11 Z9 15 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD OCT 25 PY 2005 VL 23 IS 44 BP 5177 EP 5185 DI 10.1016/j.vaccine.2005.06.014 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 976KU UT WOS:000232733100007 PM 16039021 ER PT J AU Ble, A Fink, JC Woodman, RC Klausner, MA Windham, BG Guralnik, JM Ferrucci, L AF Ble, A Fink, JC Woodman, RC Klausner, MA Windham, BG Guralnik, JM Ferrucci, L TI Renal function, erythropoietin, and anemia of older persons - The InCHIANTI study SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH; PHYSICAL PERFORMANCE; UNITED-STATES; EPIDEMIOLOGY; POPULATION; INSUFFICIENCY; PREVALENCE; FAILURE; DECLINE AB Background: In the older population, anemia has been associated with poor outcomes including disability and mortality. Understanding the mechanisms leading to anemia is essential to plan better treatment and prevention strategies. We tested the hypothesis that the age-related decline in kidney function is associated with an increased prevalence of anemia and that such an increase is accompanied by a concomitant decrement in erythro-poietin levels. Methods: Data were from the InCHIANTI study, a population-based study performed in a sample of community-dwelling older (>= 65 years) persons living in Italy. This analysis included 1005 participants with complete data on hemoglobin and erythropoietin levels and markers of renal function. Results: The prevalence of anemia according to the World Health Organization criteria (hemoglobin level < 12 g/dL for women and < 13 g/dL for men) was 12.0% and increased with age in both sexes. After adjusting for age, diseases, and other confounders, only participants with a creatinine clearance (CrCl) of 30 mL/min or lower (<= 0.50 mL/s) had a higher prevalence of anemia compared with those with a CrCl higher than 90 mL/min (> 1.50 mL/s) (P <.01). Consistently, participants with a CrCl of 30 mL/min or lower (<= 0.50 mL/s) had significantly lower age- and hemoglobin-adjusted erythropoietin endogenous levels, After excluding men and women with CrCl of 30 mL/min or lower (<= 0.50 mLs) and adjusting for confounders, we found a trend toward an increase in prevalence of anemia with decreasing renal function; however-it was not statistically significant. Conclusions: Severe age-related decline in renal function is associated with a reduced erythropoietin secretion and anemia. Whether moderate kidney impairment in older persons is associated with a progressively increasing risk of anemia remains to be determined. C1 NIA, Longitudinal Studies Sect, NIH, Baltimore, MD 21224 USA. Univ Maryland Med Syst, Div Nephrol, Baltimore, MD USA. Ortho Biotech Clin Affairs, LLC, Bridgewater, NJ USA. NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA. RP Ferrucci, L (reprint author), Harbor Hosp, NIA, 5th Floor,3001 S Hanover St, Baltimore, MD 21225 USA. EM ferruccilu@grc.nia.nih.gov OI Fink, Jeffrey/0000-0002-5622-5052 FU NIMHD NIH HHS [263 MD 9164 13, 263 MD 821336] NR 22 TC 62 Z9 67 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD OCT 24 PY 2005 VL 165 IS 19 BP 2222 EP 2227 DI 10.1001/archinte.165.19.2222 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 976US UT WOS:000232759500009 PM 16246987 ER PT J AU Jee, SH Boulware, LE Guallar, E Suh, I Appel, LJ Miller, ER AF Jee, SH Boulware, LE Guallar, E Suh, I Appel, LJ Miller, ER TI Direct, progressive association of cardiovascular risk factors with incident proteinuria - Results from the Korea Medical Insurance Corporation (KMIC) Study SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID DEPENDENT DIABETES-MELLITUS; CORONARY-HEART-DISEASE; STAGE RENAL-DISEASE; BLOOD-PRESSURE; SERUM-CHOLESTEROL; PROGNOSTIC-SIGNIFICANCE; PROSPECTIVE COHORT; CIGARETTE-SMOKING; KIDNEY-DISEASE; MEN AB Background: Proteinuria is a major risk factor for the progression of kidney disease and the development of cardiovascular disease. Little is known, however, about risk factors for incident proteinuria. Methods: We conducted a 10-year prospective cohort study of 104 523 Korean men and 52 854 women, aged 35 to 59 years, who attended Korea Medical Insurance Corporation health examinations and who did not have proteinuria at baseline. Incident proteinuria was assessed at biennial examinations during the next 10 years. We performed Cox proportional hazards analyses. Results: During 10 years of follow-up, proteinuria developed in 3951 men (3.8%) and 1527 women (2.9%). The adjusted relative risk (RR) of proteinuria associated with diabetes was 3.27 (95% confidence interval [CI], 2.98-3.58) in men and 2.60 (95% CI, 1.98-3.43) in women; with body mass index (calculated as weight in kilograms divided by the square of height in meters), it was 1.43 (95% CI, 1.35-1.50) in men and 1.45 (95% CI, 1.35-1.55) in women per 5-U increment. Compared with subjects with serum cholesterol levels of less than 200 mg/dL (< 5.18 mmol/L), the adjusted RRs associated with serum cholesterol levels of 200 to 239 mg/dL (5.18-6.19 mmol/L) and 240 mg/dL or more (>= 6.22 mmol/L) were 1.13 (95% CI, 1.05-1.21) and 1.40 (95% CI, 1.27-1.54), respectively, in men and 1.14 (95% CI, 1.01-1.28) and 1.22 (95% CI, 1.00-1.37), respectively, in women. Persons with stages I and 2 hypertension had a greater adjusted RR of incident proteinuria compared with those with normal blood pressure (1.62 [95% CI, 1.47-1.79] and 2.06 [95% CI, 1.81-2.34], respectively, in men and 1.37 [95% CI, 1.14-1.65] and 2.10 [95% CI, 1.59-2.76], respectively, in women). Conclusions: Fasting glucose and cholesterol levels, body mass index, and blood pressure were direct and independent predictors of incident proteinuria in Korean adults. These associations were present even at low levels of exposure, emphasizing the importance of early detection and management of these modifiable risk factors. C1 Yonsei Univ, Grad Sch Publ Hlth, Dept Epidemiol & Hlth Promot, Seoul 120749, South Korea. Yonsei Univ, Coll Med, Dept Prevent Med & Publ Hlth, Seoul 120749, South Korea. Johns Hopkins Sch Med, Dept Med, Baltimore, MD USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. Johns Hopkins Med Inst, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD 21205 USA. RP Miller, ER (reprint author), NIA, Clin Res Branch, Intramural Res Program, 3001 S Hanover St, Baltimore, MD 21225 USA. EM ermiller@jhmi.edu RI Guallar, Eliseo/D-3807-2014 OI Guallar, Eliseo/0000-0002-4471-9565 NR 50 TC 26 Z9 27 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD OCT 24 PY 2005 VL 165 IS 19 BP 2299 EP 2304 DI 10.1001/archinte.165.19.2299 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 976US UT WOS:000232759500021 PM 16246998 ER PT J AU Bobay, BG Andreeva, A Mueller, GA Cavanagh, J Murzin, AG AF Bobay, BG Andreeva, A Mueller, GA Cavanagh, J Murzin, AG TI Revised structure of the AbrB N-terminal domain unifies a diverse superfamily of putative DNA-binding proteins SO FEBS LETTERS LA English DT Article DE NMR solution structure; protein-DNA interactions; structural genomics; structural classification of proteins ID STATE REGULATOR ABRB; ESCHERICHIA-COLI; SEQUENTIAL ASSIGNMENT; CRYSTAL-STRUCTURE; DATABASE; SYSTEM; RECOGNITION; HOMOLOGY; PLASMID; MODULE AB New relationships found in the process of updating the structural classification of proteins (SCOP) database resulted in the revision of the structure of the N-terminal, DNA-binding domain of the transition state regulator AbrB. The dimeric AbrB domain shares a common fold with the addiction antidote MazE and the subunit of uncharacterized protein MraZ implicated in cell division and cell envelope formation. It has a detectable sequence similarity to both MazE and MraZ thus providing an evolutionary link between the two proteins. The putative DNA-binding site of AbrB is found on the same face as the DNA-binding site of MazE and appears similar, both in structure and sequence, to the exposed conserved region of MraZ. This strongly suggests that MraZ also binds DNA and allows for a consensus model of DNA recognition by the members of this novel protein superfamily. (c) 2005 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies. C1 MRC, Ctr Prot Engn, Cambridge CB2 2QH, England. N Carolina State Univ, Dept Mol & Struct Biochem, Raleigh, NC 27695 USA. Natl Inst Environm Hlth Res, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. RP Cavanagh, J (reprint author), MRC, Ctr Prot Engn, Hills Rd, Cambridge CB2 2QH, England. EM john_cavanagh@ncsu.edu; agm@mrc-lmb.cam.ac.uk OI Bobay, Benjamin/0000-0003-4775-3686 FU Intramural NIH HHS; NIGMS NIH HHS [GM55769] NR 30 TC 28 Z9 28 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD OCT 24 PY 2005 VL 579 IS 25 BP 5669 EP 5674 DI 10.1016/j.febslet.2005.09.045 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 977ST UT WOS:000232824200038 PM 16223496 ER PT J AU Ostroumova, OS Malev, VV Kaulin, YA Gurnev, PA Takemoto, JY Schagina, L AF Ostroumova, OS Malev, VV Kaulin, YA Gurnev, PA Takemoto, JY Schagina, L TI Voltage-dependent synchronization of gating of syringomycin E ion channels SO FEBS LETTERS LA English DT Article DE bilayer lipid membrane; syringomycin E; ion channels; cluster organization of ion channels ID PLANAR LIPID BILAYERS; SYRINGAE PV. SYRINGAE; CLUSTER ORGANIZATION; CONDUCTANCE STATES; CHLORIDE CHANNELS; K+ CHANNELS; SINGLE; MEMBRANES; LIPODEPSIPEPTIDE; SYRINGOPEPTIN AB Antifungal lipodepsipeptide syringomycin E (SRE) forms two major conductive states in lipid bilayers: "small" and "large". Large SRE channels are cluster of several small ones, demonstrating synchronous opening and closure. To get insight into the mechanism of such synchronization we investigated how transmembrane potential, membrane surface charge, and ionic strength affect the number of small SIZE channels synchronously functioning in the cluster. Here, we report that the large SIZE channels can be presented as 3-8 simultaneously gating small channels. The increase in the absolute value of the transmembrane potential (from 50 to 200 mV) decreases the number of synchronously gated channels in the clusters. Voltage-dependence of channel synchronization was influenced by the ionic strength of the bathing solution, but not by membrane surface charge. We propose a mechanism for the voltage-dependent cluster behavior that involves a voltage-induced reorientation of lipid dipoles associated with the channel pores. (c) 2005 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies. C1 Russian Acad Sci, Inst Cytol, St Petersburg 194064, Russia. St Petersburg State Univ, St Petersburg, Russia. Thomas Jefferson Univ, Jefferson Med Coll, Dept Pathol Anat & Cell Biol, Philadelphia, PA 19107 USA. NICHHD, NIH, Bethesda, MD 20892 USA. Utah State Univ, Logan, UT 84322 USA. RP Kaulin, YA (reprint author), Russian Acad Sci, Inst Cytol, St Petersburg 194064, Russia. EM yuri.kaulin@jefferson.edu RI Ostroumova, Olga/N-8636-2013; Takemoto, Jon/A-5309-2011 OI Takemoto, Jon/0000-0001-9919-9168 NR 26 TC 8 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD OCT 24 PY 2005 VL 579 IS 25 BP 5675 EP 5679 DI 10.1016/j.febslet.2005.08.087 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 977ST UT WOS:000232824200039 PM 16219309 ER PT J AU Sheng, Y Li, J Dufau, ML Tsai-Morris, CH AF Sheng, Y Li, J Dufau, ML Tsai-Morris, CH TI The gonadotropin-regulated long-chain acyl CoA synthetase gene: A novel downstream Sp1/Sp3 binding element critical for transcriptional promoter activity SO GENE LA English DT Article DE GR-LACS; genomic organization; transcription; testis ID RNA-POLYMERASE-II; TATA; ADRENOLEUKODYSTROPHY; INITIATOR; CLONING; BETA; DPE; SP1 AB The 79 kD gonadotropin-regulated testicular long chain acyl-CoA synthetase gene (GR-LACS) is a hormone-regulated member of the acyl-CoA synthetase family that is expressed abundantly in Leydig cells and to a lesser extent in germinal cells of the adult testis. GR-LACS possesses an ATP/AMP binding domain and the fatty acyl-CoA synthetase (FACS) signature motif, To gain insights into the transcriptional regulation of GR-LACS in gonadal cells, we determined the genomic organization of the gene, including the Upstream flanking sequences. The mouse GR-LACS gene spans over at least 45 kb and the coding region is encoded by exons 1-14. All exon intron junction sites correspond to the consensus splice sequence GT-AG. Exon 7 and 11 comprise the conserved ATP/AMP binding domain and the FACS signature motif, respectively. Primer extension and S I nuclease analyses demonstrated flour transcriptional start sites located at -266/-216 bp 5' to the ATG codon. The minimal promoter domain resides within -254/-217 bp 5' to ATG codon. and upstream sequences to -404 bp (-1035/-405 bp) contribute to the inhibition of transcription in the expressing mouse Leydig tumor cells, Removal of -217/-1 bp, containing a 23 nt GC rich sequence (-112/-90) with an Sp1/Sp3 binding element, within the 1st exon of this TATA-less promoter, significantly reduced GR-LACS gene transcription, Transcriptional activity was abolished by a 2 nt mutation of this element. Thus, functional analyses of this promoter domain indicate that transcription of GR-LACS gene requires an Sp1/Sp3 binding element downstream of the transcriptional start sites which is essential for basal promoter activity, Published by Elsevier B.V. C1 NICHD, ERRB, Sect Mol Endocrinol, NIH, Bethesda, MD 20892 USA. RP Tsai-Morris, CH (reprint author), NICHD, ERRB, Sect Mol Endocrinol, NIH, Bldg 49-6A-36,49 Convent Dr,MSC 4510, Bethesda, MD 20892 USA. EM morrisch@mail.nih.gov NR 20 TC 6 Z9 7 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD OCT 24 PY 2005 VL 360 IS 1 BP 20 EP 26 DI 10.1016/j.gene.2005.07.006 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 980FQ UT WOS:000233000000002 PM 16125341 ER PT J AU Wu, XS Tsan, GL Hammer, JA AF Wu, XS Tsan, GL Hammer, JA TI Melanophilin and myosin Va track the microtubule plus end on EB1 SO JOURNAL OF CELL BIOLOGY LA English DT Article ID MELANOSOME TRANSPORT; IN-VIVO; SLAC2-A/MELANOPHILIN; MELANOCYTES; PROTEINS; RECEPTOR; SPINDLE; RAB27A; FAMILY; APC AB In mouse melanocytes, myosin Va is recruited onto the surface of melanosomes by a receptor complex containing Rab27a that is present in the melanosome membrane and melanophilin (Mlp), which links myosin Va to Rab27a. In this study, we show that Mlp is also a microtubule plus end-tracking protein or +TIP. Moreover, myosin Va tracks the plus end in a Mlp-dependent manner. Data showing that overexpression and short inhibitory RNA knockdown of the +TIP EB1 have opposite effects on Mlp-microtubule interaction, that Mlp interacts directly with EB1, and that deletion from Mlp of a region similar to one in the adenomatous polyposis coli protein involved in EB1 binding blocks Mlp's ability to plus end track argue that Mlp tracks the plus end directly by hitchhiking on EB1. These results identify a novel +TIP and indicate that vertebrate cells possess a +TIP complex that is similar to the Myo2p-Kar9p-Bim1p complex in yeast. We suggest that the +TIP complex identified in this study may serve to focus the transfer of melanosomes from microtubules to actin at the microtubule plus end. C1 NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Hammer, JA (reprint author), NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. EM hammerj@nhlbi.nih.gov NR 16 TC 67 Z9 70 U1 0 U2 4 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD OCT 24 PY 2005 VL 171 IS 2 BP 201 EP 207 DI 10.1083/jcb.200503028 PG 7 WC Cell Biology SC Cell Biology GA 981UH UT WOS:000233113000005 PM 16247022 ER PT J AU Freudzon, L Norris, RP Hand, AR Tanaka, S Saeki, Y Jones, TLZ Rasenick, MM Berlot, CH Mehlmann, LM Jaffe, LA AF Freudzon, L Norris, RP Hand, AR Tanaka, S Saeki, Y Jones, TLZ Rasenick, MM Berlot, CH Mehlmann, LM Jaffe, LA TI Regulation of meiotic prophase arrest in mouse oocytes by GPR3, a constitutive activator of the G(s) G protein SO JOURNAL OF CELL BIOLOGY LA English DT Article ID INDUCED SUBCELLULAR REDISTRIBUTION; ADENYLATE-CYCLASE; FOLLICULAR-FLUID; FLUORESCENT PROTEIN; COUPLED RECEPTORS; MOLECULAR-CLONING; MAMMALIAN OOCYTES; ALPHA-SUBUNITS; KINASE-A; IN-VITRO AB he arrest of meiotic prophase in mouse oocytes within antral follicles requires the G protein G(s) and an orphan member of the G protein-coupled receptor family, GPR3. To determine whether GPR3 activates G(s), the localization of G(alpha s) in follicle-enclosed oocytes from Gpr3(+/+) and Gpr3(-/-) mice was compared by using immunofluorescence and G(alpha s) GFP. GPR3 decreased the ratio of G(alpha s) in the oocyte plasma membrane versus the cytoplasm and also decreased the amount of G(alpha s) in the oocyte. Both of these properties indicate that GPR3 activates G(s). The follicle cells around the oocyte are also necessary to keep the oocyte in prophase, suggesting that they might activate GPR3. However, GPR3-dependent G(s) activity was similar in follicle-enclosed and follicle-free oocytes. Thus, the maintenance of prophase arrest depends on the constitutive activity of GPR3 in the oocyte, and the follicle cell signal acts by a means other than increasing GPR3 activity. C1 Univ Connecticut, Ctr Hlth, Dept Cell Biol, Farmington, CT 06032 USA. Univ Connecticut, Ctr Hlth, Dept Pediat Dent, Farmington, CT 06032 USA. Ohio State Univ, Dept Neurol Surg, Columbus, OH 43210 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. Univ Illinois, Dept Physiol & Biophys, Chicago, IL 60612 USA. Univ Illinois, Dept Psychiat, Chicago, IL 60612 USA. Weis Ctr Res, Geisinger Clin, Danville, PA 17822 USA. RP Jaffe, LA (reprint author), Univ Connecticut, Ctr Hlth, Dept Cell Biol, Farmington, CT 06032 USA. EM ljaffe@neuron.uchc.edu RI Tanaka, Shigeru/O-3908-2015 FU NCRR NIH HHS [P41 RR013186, RR13186]; NICHD NIH HHS [HD14939, R37 HD014939, R01 HD014939]; NIDDK NIH HHS [R01 DK073499, DK073499]; NIGMS NIH HHS [GM50369, R01 GM050369, R29 GM050369]; NIMH NIH HHS [R01 MH039595, MH39595]; NINDS NIH HHS [NS445140] NR 53 TC 56 Z9 57 U1 1 U2 4 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD OCT 24 PY 2005 VL 171 IS 2 BP 255 EP 265 DI 10.1083/jcb.200506194 PG 11 WC Cell Biology SC Cell Biology GA 981UH UT WOS:000233113000010 PM 16247026 ER PT J AU Giddens, AC Boshoff, HIM Franzblau, SG Barry, CE Copp, BR AF Giddens, AC Boshoff, HIM Franzblau, SG Barry, CE Copp, BR TI Antimycobacterial natural products: synthesis and preliminary biological evaluation of the oxazole-containing alkaloid texaline SO TETRAHEDRON LETTERS LA English DT Article DE texaline; alkaloid; tuberculosis; natural product ID TB AB Texaline, an antimycobacterial oxazole-containing alkaloid previously isolated from Amyris texana and A. elemifera, and related compounds have been synthesized in order to explore aspects of the structure-anti tuberculosis activity relationship. While texaline was found to be inactive in our assays, simpler diaryloxazoles were more active whilst also exhibiting modest toxic selectivity, leading to their identification as potential lead compounds. (c) 2005 Elsevier Ltd. All rights reserved. C1 Univ Auckland, Dept Chem, Auckland, New Zealand. NIAID, TB Res Sect, NIH, Rockville, MD 20852 USA. Univ Illinois, Coll Pharm, Inst TB Res, Chicago, IL 60612 USA. RP Copp, BR (reprint author), Univ Auckland, Dept Chem, Private Bag 92019, Auckland, New Zealand. EM b.copp@auckland.ac.nz RI Copp, Brent/D-3706-2009; Barry, III, Clifton/H-3839-2012; OI Copp, Brent/0000-0001-5492-5269; Franzblau, Scott/0000-0002-8698-0243 NR 14 TC 45 Z9 45 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0040-4039 J9 TETRAHEDRON LETT JI Tetrahedron Lett. PD OCT 24 PY 2005 VL 46 IS 43 BP 7355 EP 7357 DI 10.1016/j.tetlet.2005.08.119 PG 3 WC Chemistry, Organic SC Chemistry GA 972EQ UT WOS:000232437400016 ER PT J AU Berlin, CM LaKind, JS Fenton, SE Wang, RY Bates, MN Brent, RL Condon, M Crase, BL Dourson, ML Ettinger, AS Foos, B Furst, P Giacoia, GP Goldstein, DA Haynes, SG Hench, KD Kacew, S Koren, G Lawrence, RA Mason, A McDiarmid, MA Moy, G Needham, LL Paul, IM Pugh, LC Qian, ZM Salamone, L Selevan, SG Sonawane, B Tarzian, AJ Tully, MR Uhl, K AF Berlin, CM LaKind, JS Fenton, SE Wang, RY Bates, MN Brent, RL Condon, M Crase, BL Dourson, ML Ettinger, AS Foos, B Furst, P Giacoia, GP Goldstein, DA Haynes, SG Hench, KD Kacew, S Koren, G Lawrence, RA Mason, A McDiarmid, MA Moy, G Needham, LL Paul, IM Pugh, LC Qian, ZM Salamone, L Selevan, SG Sonawane, B Tarzian, AJ Tully, MR Uhl, K TI Conclusions and recommendations of the expert panel: Technical Workshop on Human Milk Surveillance and Biomonitoring for Environmental Chemicals in the United States SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES LA English DT Article; Proceedings Paper CT Workshop on Human Milk Surveillance and Research on Environmental Chemicals in the United States CY SEP 24-26, 2004 CL Pennsylvania State Univ, Coll Med, Hershey, PA HO Pennsylvania State Univ, Coll Med C1 Penn State Univ, Milton S Hershey Med Ctr, Coll Med, Dept Pediat, Hershey, PA 17033 USA. LaKind Associates LLC, Catonsville, MD USA. US EPA, Natl Hlth & Environm Effects Res Lab, Off Res & Dev, Res Triangle Pk, NC 27711 USA. Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA USA. Univ Calif Berkeley, Sch Publ Hlth, Div Environm Hlth Sci, Berkeley, CA 94720 USA. AI duPont Hosp Children, Wilmington, DE USA. Univ Maryland, Sch Med, Occupat Hlth Program, Baltimore, MD 21201 USA. Amer Acad Pediat, Div Community Hlth Serv, Breastfeeding Initiat, Elk Grove Village, IL USA. Toxicol Excellence Risk Assessment, Cincinnati, OH USA. Harvard Univ, Sch Publ Hlth, Exposure Epidemiol & Risk Program, Boston, MA 02115 USA. US EPA, Off Childrens Hlth Protect, Washington, DC 20460 USA. Chem & Vet Control Lab, Munster, Germany. NICHHD, Pediat Pharmacol Res Unit Network, NIH, Rockville, MD USA. Monsanto Co, St Louis, MO USA. Dept Hlth & Human Serv, Off Womens Hlth, Washington, DC USA. US PHS, Div Perinatal Syst, Rockville, MD USA. US Hlth Resources & Serv Adm, Womens Hlth Maternal & Child Hlth Bur, Rockville, MD 20857 USA. Univ Ottawa, Dept Pharmacol, Ottawa, ON, Canada. Univ Western Ontario, Hosp Sick Children Mol Toxicol, Div Clin Pharmacol & Toxicol, London, ON N6A 3K7, Canada. Univ Rochester, Breastfeeding & Human Lactat Study Ctr, Golisano Childrens Hosp, Rochester, NY USA. Res Fdn Hlth & Environm Effects, Arlington, VA USA. WHO, CH-1211 Geneva, Switzerland. Penn State Univ, Milton S Hershey Med Ctr, Coll Med, Dept Pediat, Hershey, PA 17033 USA. Penn State Univ, Milton S Hershey Med Ctr, Coll Med, Dept Hlth Evaluat Sci, Hershey, PA 17033 USA. Johns Hopkins Univ, Sch Nursing, Baltimore, MD USA. Amer Chem Council, Hlth Prod & Sci Policy Team, Arlington, VA USA. US EPA, Natl Ctr Environm Assessment, Off Res & Dev, Washington, DC 20460 USA. Eth & Res Consultant, Baltimore, MD USA. Univ Maryland, Sch Law, Law & Hlth Care Program, Baltimore, MD 21201 USA. Univ Maryland, Sch Nursing, Baltimore, MD 21201 USA. Univ N Carolina Hlth Care, N Carolina Womens Hosp, Human Milk Banking Associat N Amer, Chapel Hill, NC USA. US FDA, Ctr Drug Evaluat & Res, Off New Drugs, Pregnancy Labeling Team, Rockville, MD 20857 USA. RP Berlin, CM (reprint author), Penn State Univ, Milton S Hershey Med Ctr, Coll Med, Childrens Hosp,Dept Pediat, MC HO85,POB 850, Hershey, PA 17033 USA. EM cmb6@psu.edu OI Paul, Ian/0000-0002-6344-8609 NR 2 TC 11 Z9 11 U1 0 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1528-7394 J9 J TOXICOL ENV HEAL A JI J. Toxicol. Env. Health Part A PD OCT 22 PY 2005 VL 68 IS 20 BP 1825 EP 1831 DI 10.1080/15287390500226896 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 969ZV UT WOS:000232275900007 PM 16176920 ER PT J AU Monje, P Hernandez-Losa, J Lyons, RJ Castellone, MD Gutkind, JS AF Monje, P Hernandez-Losa, J Lyons, RJ Castellone, MD Gutkind, JS TI Regulation of the transcriptional activity of c-Fos by ERK: A novel role for the prolyl isomerase Pin1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACTIVATED PROTEIN-KINASE; SIGNAL-TRANSDUCTION PATHWAYS; CELLULAR-TRANSFORMATION; GROWTH-FACTOR; JUN PROMOTER; PHOSPHORYLATION; AP-1; DOMAINS AB The activation of the activating protein-1 (AP-1) family of transcription factors, including c-Fos and c-Jun family members, is one of the earliest nuclear events induced by growth factors that stimulate extracellular signal-regulated kinases (ERKs). In the case of c-Fos, the activation of ERK leads to an increased expression of c-fos mRNA. In turn, we have recently shown that ERK phosphorylates multiple residues within the carboxyl-terminal transactivation domain (TAD) of c-Fos, thus resulting in its increased transcriptional activity. However, how ERK-dependent phosphorylation regulates c-Fos function is still poorly understood. In this regard, it has been recently observed that the prolyl isomerase Pin1 can interact with proteins phosphorylated on serine or threonine residues that precede prolines (pS/T-P), such as the transcription factors p53 and c-Jun, thereby controlling their activity by promoting the cis-trans isomerization of these pS/T-P bonds. Here, we found that Pin1 binds c-Fos through specific pS/T-P sites within the c-Fos TAD, and that this interaction results in an enhanced transcriptional response of c-Fos to polypeptide growth factors that stimulate ERK. Our findings suggest that c-Fos represents a novel target for the isomerizing activity of Pin1 and support a role for Pin1 in the mechanism by which c-Jun and c-Fos can cooperate to regulate AP-1-dependent gene transcription upon phosphorylation by mitogen-activated kinase (MAPK) family members. C1 NIDCR, Oral & Pharyngeal Canc Branch, NIH, DHHS, Bethesda, MD 20892 USA. RP Gutkind, JS (reprint author), NIDCR, Oral & Pharyngeal Canc Branch, NIH, DHHS, 30 Convent Dr,Bldg 30,Rm 211, Bethesda, MD 20892 USA. EM sg39v@nih.gov RI Gutkind, J. Silvio/A-1053-2009; Javier, Hernandez Losa/C-1173-2008; OI Javier, Hernandez Losa/0000-0003-1526-3201; CASTELLONE, MARIADOMENICA/0000-0003-0507-8037 FU Intramural NIH HHS NR 17 TC 135 Z9 139 U1 1 U2 11 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 21 PY 2005 VL 280 IS 42 BP 35081 EP 35084 DI 10.1074/jbc.C500353200 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 973ZN UT WOS:000232561200003 PM 16123044 ER PT J AU Grinchuk, O Kozmik, Z Wu, XF Tomarev, S AF Grinchuk, O Kozmik, Z Wu, XF Tomarev, S TI The Optimedin gene is a downstream target of Pax6 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRABECULAR MESHWORK CELLS; OLFACTOMEDIN-RELATED PROTEIN; HOMEOBOX-CONTAINING GENE; SEQUENCE TAG ANALYSIS; OPEN-ANGLE GLAUCOMA; DNA-BINDING; ALPHA-LATROTOXIN; SECRETED GLYCOPROTEIN; EXPRESSION PROFILE; COUPLED RECEPTORS AB The Optimedin gene, also known as Olfactomedin 3, encodes an olfactomedin domain-containing protein. There are two major splice variants of the Optimedin mRNA, Optimedin A and Optimedin B, transcribed from different promoters. The expression pattern of the Optimedin A variant in the eye and brain overlaps with that for Pax6, which encodes a protein containing the paired and homeobox DNA-binding domains. The Pax6 gene plays a critical role for the development of eyes, central nervous system, and endocrine glands. The proximal promoter of the Optimedin A variant contains a putative Pax6 binding site in position -86/-70. Pax6 binds this site through the paired domain in vitro as judged by electrophoretic mobility shift assay. Mutations in this site eliminate Pax6 binding as well as stimulation of the Optimedin promoter activity by Pax6 in transfection experiments. Pax6 occupies the binding site in the proximal promoter in vivo as demonstrated by the chromatin immunoprecipitation assay. Altogether these results identify the Optimedin gene as a downstream target regulated by Pax6. Although the function of optimedin is still not clear, it is suggested to be involved in cell-cell adhesion and cell attachment to the extracellular matrix. Pax6 regulation of Optimedin in the eye and brain may directly affect multiple developmental processes, including cell migration and axon growth. C1 NEI, Sect Mol Mech Glaucoma, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. Acad Sci Czech Republ, Inst Mol Genet, CR-14220 Prague, Czech Republic. RP Tomarev, S (reprint author), Bldg 7,Rm 103,7 Mem Dr,MSC 0704, Bethesda, MD 20892 USA. EM tomarevs@nei.nih.gov RI Kozmik, Zbynek/G-3581-2014; Kozmik, Zbynek/I-8807-2014 FU Intramural NIH HHS NR 76 TC 21 Z9 22 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 21 PY 2005 VL 280 IS 42 BP 35228 EP 35237 DI 10.1074/jbc.M506195200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 973ZN UT WOS:000232561200020 PM 16115881 ER PT J AU Tzeng, SJ Bolland, S Inabe, K Kurosaki, T Pierce, SK AF Tzeng, SJ Bolland, S Inabe, K Kurosaki, T Pierce, SK TI The B cell inhibitory Fc receptor triggers apoptosis by a novel c-Abl family kinase-dependent pathway SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TYROSINE KINASES; ANTIGEN RECEPTOR; DISEASE; SIGNALS AB The inhibitory Fc receptors function to regulate the antigen-driven activation and expansion of lymphocytes. In B cells, the Fc gamma RIIB1 is a potent inhibitor of B cell antigen receptor (BCR) signaling when coligated to the BCR by engagement of antigen-containing immune complexes. Inhibition is mediated by the recruitment of the inositol phosphatase, SHIP, to the Fc gamma RIIB1 phosphorylated tyrosine-based inhibitory motif (ITIM). Here we show that BCR-independent aggregation of the Fc gamma RIIB1 transduces an ITIM- and SHIP-independent proapoptotic signal that is dependent on members of the c-Abl tyrosine kinase family. These results define a novel Abl family kinase-dependent Fc gamma RIIB1 signaling pathway that functions independently of the BCR in controlling antigen-driven B cell responses. C1 NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. Kansai Med Univ, Inst Liver Res, Dept Mol Genet, Moriguchi, Osaka 5708506, Japan. RIKEN, Res Ctr Allergy & Immunol, Lab Lymphocyte Differentiat, Tsurumi Ku, Kanagawa 2300045, Japan. RP Pierce, SK (reprint author), NIAID, Immunogenet Lab, NIH, Twinbrook 2,12441 Parklawn Dr,Rm 200B,MSC 8180, Rockville, MD 20852 USA. EM spierce@nih.gov RI Kurosaki, Tomohiro/D-1306-2009; OI Kurosaki, Tomohiro/0000-0002-6352-304X; Tzeng, Shiang-Jong/0000-0003-1633-020X FU Intramural NIH HHS NR 20 TC 39 Z9 42 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 21 PY 2005 VL 280 IS 42 BP 35247 EP 35254 DI 10.1074/jbc.M505308200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 973ZN UT WOS:000232561200022 PM 16115887 ER PT J AU Lievremont, JP Numaga, T Vazquez, G Lemonnier, L Hara, Y Mori, E Trebak, M Moss, SE Bird, GS Mori, Y Putney, JW AF Lievremont, JP Numaga, T Vazquez, G Lemonnier, L Hara, Y Mori, E Trebak, M Moss, SE Bird, GS Mori, Y Putney, JW TI The role of canonical transient receptor potential 7 in B-cell receptor-activated channels SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SMOOTH-MUSCLE-CELLS; CAPACITATIVE CALCIUM-ENTRY; INDUCED CA2+ ENTRY; TRANSIENT RECEPTOR; TRPC3 CHANNELS; CATION ENTRY; ENDOPLASMIC-RETICULUM; RELEASE; LYMPHOCYTES; EXPRESSION AB Phospholipase C signaling stimulates Ca2+ entry across the plasma membrane through multiple mechanisms. Ca2+ store depletion stimulates store- operated Ca2+- selective channels, or alternatively, other phospholipase C- dependent events activate Ca2+- permeable non- selective cation channels. Transient receptor potential 7 ( TRPC7) is a non- selective cation channel that can be activated by both mechanisms when ectopically expressed, but the regulation of native TRPC7 channels is not known. We knocked out TRPC7 in DT40 B- cells, which expresses both forms of Ca2+ entry. No difference in the store- operated current I-crac was detected between TRPC7 (-/-) and wild- type cells. Wild- type cells demonstrated non-store-operated cation entry and currents in response to activation of the B- cell receptor or protease- activated receptor 2, intracellular dialysis with GTP gamma S, or application of the synthetic diacylglycerol oleyl- acetyl- glycerol. These responses were absent in TRPC7 (-/-) cells but could be restored by transfection with human TRPC7. In conclusion, in B- lymphocytes, TRPC7 appeared to participate in the formation of ion channels that could be activated by phospholipase C- linked receptors. This represents the first demonstration of a physiological function for endogenous TRPC7 channels. C1 NIEHS, Dept Hlth & Human Serv, NIH, Res Triangle Pk, NC 27709 USA. Kyoto Univ, Grad Sch Engn, Dept Synthet Chem & Biol Chem, Mol Biol Lab, Kyoto 6158510, Japan. UCL, Inst Ophthalmol, Div Cell Biol, London EC1V 9EL, England. RP Putney, JW (reprint author), NIEHS, Dept Hlth & Human Serv, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM putney@niehs.nih.gov RI Trebak, Mohamed/E-7405-2014 NR 31 TC 35 Z9 41 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 21 PY 2005 VL 280 IS 42 BP 35346 EP 35351 DI 10.1074/jbc.M507606200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 973ZN UT WOS:000232561200033 PM 16123040 ER PT J AU Kang, SG Dimitrova, MN Ortega, JQ Ginsburg, A Maurizi, MR AF Kang, SG Dimitrova, MN Ortega, JQ Ginsburg, A Maurizi, MR TI Human mitochondrial ClpP is a stable heptamer that assembles into a tetradecamer in the presence of ClpX SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ATP-DEPENDENT PROTEASES; ESCHERICHIA-COLI; MOLECULAR CHAPERONE; REGULATORY SUBUNITS; DEGRADATION MACHINE; PROTEIN-BINDING; BACTERIAL CLPX; AMINO-ACID; PROTEOLYSIS; SPECIFICITY AB The functional form of ClpP, the proteolytic component of ATP-dependent Clp proteases, is a hollow- cored particle composed of two heptameric rings joined face- to- face forming an aqueous chamber containing the proteolytic active sites. We have found that isolated human mitochondrial ClpP ( hClpP) is stable as a heptamer and remains a monodisperse species ( s(20,w) 7.0 S; M-app 169, 200) at concentrations >= 3 mg/ ml. Heptameric hClpP has no proteolytic activity and very low peptidase activity. In the presence of ATP, hClpX interacts with hClpP forming a complex, which by equilibrium sedimentation measurements has a M-app of 1 x 10(6). Electron microscopy confirmed that the complex consisted of a double ring of hClpP with an hClpX ring axially aligned on each end. The hClpXP complex has protease activity and greatly increased peptidase activity, indicating that interaction with hClpX affects the conformation of the hClpP catalytic active site. A mutant of hClpP, in which a cysteine residue was introduced into the handle region at the interface between the two rings formed stable tetradecamers under oxidizing conditions but spontaneously dissociated into two heptamers upon reduction. Thus, hClpP rings interact transiently but very weakly in solution, and hClpX must exert an allosteric effect on hClpP to promote a conformation that stabilizes the tetradecamer. These data suggest that hClpX can regulate the appearance of hClpP peptidase activity in mitochondria and might affect the nature of the degradation products released during ATP- dependent proteolytic cycles. C1 NCI, Cell Biol Lab, Bethesda, MD 20892 USA. NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. NIAMS, Struct Biol Lab, NIH, Bethesda, MD 20892 USA. RP Maurizi, MR (reprint author), NCI, Cell Biol Lab, Bldg 37 Rm 2128,37 Convent Dr, Bethesda, MD 20892 USA. EM mmaurizi@helix.nih.gov FU Intramural NIH HHS NR 45 TC 47 Z9 55 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 21 PY 2005 VL 280 IS 42 BP 35424 EP 35432 DI 10.1074/jbc.M507240200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 973ZN UT WOS:000232561200042 PM 16115876 ER PT J AU Lazarus, BD Roos, MD Hanover, JA AF Lazarus, BD Roos, MD Hanover, JA TI Mutational analysis of the catalytic domain of O-linked N-acetylglucosaminyl transferase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RNA-POLYMERASE-II; GIBBERELLIN SIGNAL-TRANSDUCTION; GLCNAC TRANSFERASE; INSULIN-RESISTANCE; TETRATRICOPEPTIDE REPEATS; NUCLEAR-PORE; CRYSTAL-STRUCTURE; BETA-GLUCOSYLTRANSFERASE; SUBSTRATE-SPECIFICITY; CYTOSOLIC PROTEINS AB O-Linked N-acetylglucosaminyltransferase (OGT) catalyzes the transfer of O-linked GlcNAc to serine/threonine residues of a variety of target proteins, many of which have been implicated in such diseases as diabetes and neurodegeneration. The addition of O-GlcNAc to proteins occurs in response to fluctuations in cellular concentrations of UDP-GlcNAc, which result from nutrients entering the hexosamine biosynthetic pathway. However, the molecular mechanisms involved in sugar nucleotide recognition and transfer to protein are poorly understood. We employed site-directed mutagenesis to target potentially important amino acid residues within the two conserved catalytic domains of OGT(CDI and CDII), followed by an in vitro glycosylation assay to evaluate N-acetylglucosaminyltransferase activity after bacterial expression. Although many of the amino acid substitutions caused inactivation of the enzyme, we identified three amino acid residues ( two in CD I and one in CD II) that produced viable enzymes when mutated. Structure-based homology modeling revealed that these permissive mutants may be either in or near the sugar nucleotide-binding site. Our findings suggest a model in which the two conserved regions of the catalytic domain, CDI and CDII, contribute to the formation of a UDP-GlcNAc-binding pocket that catalyzes the transfer of O-GlcNAc to substrate proteins. Identification of viable OGT mutants may facilitate examination of its role in nutrient sensing and signal transduction cascades. C1 NIDDK, Lab Cell Biol & Biochem, NIH, Bethesda, MD 20897 USA. RP Hanover, JA (reprint author), NIDDK, Lab Cell Biol & Biochem, NIH, Bldg 8,Rm 402,9000 Rockville Pike, Bethesda, MD 20897 USA. EM jah@helix.nih.gov NR 62 TC 25 Z9 26 U1 1 U2 9 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 21 PY 2005 VL 280 IS 42 BP 35537 EP 35544 DI 10.1074/jbc.M504948200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 973ZN UT WOS:000232561200055 PM 16105839 ER PT J AU Arnoult, D Grodet, A Lee, YJ Estaquier, J Blackstone, C AF Arnoult, D Grodet, A Lee, YJ Estaquier, J Blackstone, C TI Release of OPA1 during apoptosis participates in the rapid and complete release of cytochrome c and subsequent mitochondrial fragmentation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CELL-DEATH; FUSION; FISSION; BAX; ASSOCIATION; DYSFUNCTION; DYNAMICS; DRP1 AB Mitochondria are important participants in apoptosis, releasing cytochrome c into the cytoplasm and undergoing extensive fragmentation. However, mechanisms underlying these processes remain unclear. Here, we demonstrate that cytochrome c release during apoptosis precedes mitochondrial fragmentation. Unexpectedly, OPA1, a dynamin- like GTPase of the mitochondrial intermembrane space important for maintaining cristae structure, is co-released with cytochrome c. To mimic the loss of OPA1 occurring after its release, we knocked down OPA1 expression using RNA interference. This triggered structural changes in the mitochondrial cristae and caused increased fragmentation by blocking mitochondrial fusion. Because cytochrome c is mostly sequestered within cristae folds but released rapidly and completely during apoptosis, we examined the effect of OPA1 loss on cytochrome c release, demonstrating that it is accelerated. Thus, our results suggest that an initial mitochondrial leak of OPA1 leads to cristae structural alterations and exposure of previously sequestered protein pools, permitting continued release in a feed- forward manner to completion. Moreover, our findings indicate that the resulting OPA1 depletion causes a block in mitochondrial fusion, providing a compelling mechanism for the prominent increase in mitochondrial fragmentation seen during apoptosis. C1 NINDS, Cellular Neurol Unit, NIH, Bethesda, MD 20892 USA. NINDS, Biochem Sect, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. Inst Pasteur, Unite Physiopathol Infect Lentivirales, F-75724 Paris, France. Univ Paris 07, INSERM, U327, F-75018 Paris, France. RP Blackstone, C (reprint author), NINDS, Cellular Neurol Unit, NIH, Bethesda, MD 20892 USA. EM blackstc@ninds.nih.gov OI Estaquier, Jerome/0000-0002-9432-8044 FU Intramural NIH HHS; Wellcome Trust NR 27 TC 163 Z9 167 U1 1 U2 8 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 21 PY 2005 VL 280 IS 42 BP 35742 EP 35750 DI 10.1074/jbc.M505970200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 973ZN UT WOS:000232561200077 PM 16115883 ER PT J AU Tarran, R Button, B Picher, M Paradiso, AM Ribeiro, CM Lazarowski, ER Zhang, LQ Collins, PL Pickles, RJ Fredberg, JJ Boucher, RC AF Tarran, R Button, B Picher, M Paradiso, AM Ribeiro, CM Lazarowski, ER Zhang, LQ Collins, PL Pickles, RJ Fredberg, JJ Boucher, RC TI Normal and cystic fibrosis airway surface liquid homeostasis - The effects of phasic shear stress and viral infections SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RESPIRATORY SYNCYTIAL VIRUS; TRANSMEMBRANE CONDUCTANCE REGULATOR; HUMAN BRONCHIAL EPITHELIA; ION-TRANSPORT; MUCOCILIARY CLEARANCE; MUCUS CLEARANCE; LUNG-DISEASE; WILD-TYPE; PERICILIARY LIQUID; CHLORIDE SECRETION AB Mammalian airways normally regulate the volume of a thin liquid layer, the periciliary liquid ( PCL), to facilitate the mucus clearance component of lung defense. Studies under standard ( static) culture conditions revealed that normal airway epithelia possess an adenosine-regulated pathway that blends Na+ absorption and Cl- secretion to optimize PCL volume. In cystic fibrosis ( CF), the absence of CF transmembrane conductance regulator results in a failure of adenosine regulation of PCL volume, which is predicted to initiate mucus stasis and infection. However, under conditions that mimic the phasic motion of the lung in vivo, ATP release into PCL was increased, CF ion transport was rebalanced, and PCL volume was restored to levels adequate for lung defense. This ATP signaling system was vulnerable, however, to insults that trigger CF bacterial infections, such as viral ( respiratory syncitial virus) infections, which up- regulated extracellular ATPase activity and abolished motion- dependent ATP regulation of CF PCL height. These studies demonstrate ( i) how the normal coordination of opposing ion transport pathways to maintain PCL volume is disrupted in CF, ( ii) the hitherto unknown role of phasic motion in regulating key aspects of normal and CF innate airways defense, and ( iii) that maneuvers directed at increasing motion- induced nucleotide release may be therapeutic in CF patients. C1 Univ N Carolina, Cyct Fibrosis Pulm Res & Treatment Ctr, Chapel Hill, NC 27599 USA. NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Tarran, R (reprint author), Univ N Carolina, Cyct Fibrosis Pulm Res & Treatment Ctr, Chapel Hill, NC 27599 USA. EM robert_tarran@med.unc.edu RI Ribeiro, Carla Maria/A-6955-2009 FU NHLBI NIH HHS [R01 HL074158, HL074158, HL34322, HL60280, P01 HL034322, P50 HL060280, R01 HL076303, R01 HL076303-01A2] NR 61 TC 202 Z9 205 U1 1 U2 21 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 21 PY 2005 VL 280 IS 42 BP 35751 EP 35759 DI 10.1074/jbc.M505832200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 973ZN UT WOS:000232561200078 PM 16087672 ER PT J AU Omelchenko, MV Wolf, YI Gaidamakova, EK Matrosova, VY Vasilenko, A Zhai, M Daly, MJ Koonin, EV Makarova, KS AF Omelchenko, MV Wolf, YI Gaidamakova, EK Matrosova, VY Vasilenko, A Zhai, M Daly, MJ Koonin, EV Makarova, KS TI Comparative genomics of Thermus thermophilus and Deinococcus radiodurans: divergent routes of adaptation to thermophily and radiation resistance SO BMC EVOLUTIONARY BIOLOGY LA English DT Article ID HORIZONTAL GENE-TRANSFER; IONIZING-RADIATION; EXTREME RADIORESISTANCE; TEMPERATURE ADAPTATION; PYROCOCCUS-FURIOSUS; THERMOTOGA-MARITIMA; PROTEIN SEQUENCES; FERRITIN HOMOLOG; COG DATABASE; DNA-SEQUENCE AB Background: Thermus thermophilus and Deinococcus radiodurans belong to a distinct bacterial clade but have remarkably different phenotypes. T. thermophilus is a thermophile, which is relatively sensitive to ionizing radiation and desiccation, whereas D. radiodurans is a mesophile, which is highly radiation- and desiccation-resistant. Here we present an in-depth comparison of the genomes of these two related but differently adapted bacteria. Results: By reconstructing the evolution of Thermus and Deinococcus after the divergence from their common ancestor, we demonstrate a high level of post-divergence gene flux in both lineages. Various aspects of the adaptation to high temperature in Thermus can be attributed to horizontal gene transfer from archaea and thermophilic bacteria; many of the horizontally transferred genes are located on the single megaplasmid of Thermus. In addition, the Thermus lineage has lost a set of genes that are still present in Deinococcus and many other mesophilic bacteria but are not common among thermophiles. By contrast, Deinococcus seems to have acquired numerous genes related to stress response systems from various bacteria. A comparison of the distribution of orthologous genes among the four partitions of the Deinococcus genome and the two partitions of the Thermus genome reveals homology between the Thermus megaplasmid (pTT27) and Deinococcus megaplasmid (DR177). Conclusion: After the radiation from their common ancestor, the Thermus and Deinococcus lineages have taken divergent paths toward their distinct lifestyles. In addition to extensive gene loss, Thermus seems to have acquired numerous genes from thermophiles, which likely was the decisive contribution to its thermophilic adaptation. By contrast, Deinococcus lost few genes but seems to have acquired many bacterial genes that apparently enhanced its ability to survive different kinds of environmental stresses. Notwithstanding the accumulation of horizontally transferred genes, we also show that the single megaplasmid of Thermus and the DR177 megaplasmid of Deinococcus are homologous and probably were inherited from the common ancestor of these bacteria. C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. Uniformed Serv Univ Hlth Sci, F Edward Hebert Sch Med, Dept Pathol, Bethesda, MD 20814 USA. RP Makarova, KS (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. EM omelchen@ncbi.nlm.nih.gov; wolf@ncbi.nlm.nih.gov; egaidamakova@usuhs.mil; vmatrosova@usuhs.mil; avasilenko@usuhs.mil; mzhai@usuhs.mil; mdaly@usuhs.mil; koonin@ncbi.nlm.nih.gov; makarova@ncbi.nlm.nih.gov NR 98 TC 95 Z9 98 U1 3 U2 18 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2148 J9 BMC EVOL BIOL JI BMC Evol. Biol. PD OCT 20 PY 2005 VL 5 AR 57 DI 10.1186/1471-2148-5-57 PG 22 WC Evolutionary Biology; Genetics & Heredity SC Evolutionary Biology; Genetics & Heredity GA 979DQ UT WOS:000232923000001 PM 16242020 ER PT J AU Agtini, MD Soeharno, R Lesmana, M Punjabi, NH Simanjuntak, C Wangsasaputra, F Nurdin, D Pulungsih, SP Rofiq, A Santoso, H Pujarwoto, H Sjahrurachman, A Sudarmono, P von Seidlein, L Deen, JL Ali, M Lee, H Kim, DR Han, OP Park, JK Ingerani, AS Oyofo, BA Campbell, JR Beecham, HJ Corwin, AL Clemens, JD AF Agtini, MD Soeharno, R Lesmana, M Punjabi, NH Simanjuntak, C Wangsasaputra, F Nurdin, D Pulungsih, SP Rofiq, A Santoso, H Pujarwoto, H Sjahrurachman, A Sudarmono, P von Seidlein, L Deen, JL Ali, M Lee, H Kim, DR Han, OP Park, JK Ingerani, AS Oyofo, BA Campbell, JR Beecham, HJ Corwin, AL Clemens, JD TI The burden of diarrhoea, shigellosis, and cholera in North Jakarta, Indonesia: findings from 24 months surveillance SO BMC INFECTIOUS DISEASES LA English DT Article ID VIBRIO-PARAHAEMOLYTICUS; YOUNG-CHILDREN; GLOBAL PROBLEM; ENDEMIC AREA; DISEASE; MAGNITUDE AB Background: In preparation of vaccines trials to estimate protection against shigellosis and cholera we conducted a two-year community-based surveillance study in an impoverished area of North Jakarta which provided updated information on the disease burden in the area. Methods: We conducted a two-year community-based surveillance study from August 2001 to July 2003 in an impoverished area of North Jakarta to assess the burden of diarrhoea, shigellosis, and cholera. At participating health care providers, a case report form was completed and stool sample collected from cases presenting with diarrhoea. Results: Infants had the highest incidences of diarrhoea (759/ 1 000/ year) and cholera (4/1 000/ year). Diarrhea incidence was significantly higher in boys under 5 years (387/ 1 000/ year) than girls under 5 years (309/ 1 000/ year; p < 0.001). Children aged 1 to 2 years had the highest incidence of shigellosis (32/1 000/ year). Shigella flexneri was the most common Shigella species isolated and 73% to 95% of these isolates were resistant to ampicillin, trimethoprim-sulfamethoxazole, chloramphenicol and tetracycline but remain susceptible to nalidixic acid, ciprofloxacin, and ceftriaxone. We found an overall incidence of cholera of 0.5/1 000/ year. Cholera was most common in children, with the highest incidence at 4/1 000/ year in those less than 1 year of age. Of the 154 V. cholerae O1 isolates, 89 (58%) were of the El Tor Ogawa serotype and 65 (42%) were El Tor Inaba. Thirty-four percent of patients with cholera were intravenously rehydrated and 22% required hospitalization. V. parahaemolyticus infections were detected sporadically but increased from July 2002 onwards. Conclusion: Diarrhoea causes a heavy public health burden in Jakarta particularly in young children. The impact of shigellosis is exacerbated by the threat of antimicrobial resistance, whereas that of cholera is aggravated by its severe manifestations. C1 Int Vaccine Inst, Seoul, South Korea. NICHHD, Bethesda, MD 20892 USA. Natl Inst Hlth Res & Dev, Jakarta, Indonesia. Minist Hlth, Jakarta, Indonesia. USN, Med Res Unit 2, Jakarta, Indonesia. Minist Hlth, Infect Dis Hosp Sulianti Saroso, Jakarta, Indonesia. Univ Indonesia, Dept Microbiol, Jakarta, Indonesia. RP von Seidlein, L (reprint author), Int Vaccine Inst, Seoul, South Korea. EM magdarina@yahoo.com; rooswanti@litbang.depkes.go.id; murad@namru2.org; narain@namru2.org; cyrushs@hotmail.com; ferry@namru2.med.navy.mil; ferry@namru2.med.navy.mil; rspiss@idola.net.id; rofiq@idola.net.id; santoso@hotmail.com; ferry@hotmail.com; Sjahrurachman@idola.net.id; ferry@namru2.med.navy.mil; lseidlein@ivi.int; jdeen@ivi.int; mali@ivi.int; hjlee@ivi.int; drkim@ivi.int; qphan@ivi.int; jkpark@ivi.int; ingerani@hotmail.com; oyofoba@namru2.med.navy.mil; campbelljr@namru2.med.navy.mil; beechamjh@namru2.med.navy.mil; corwinal@namru2.med.navy.mil; jclemens@ivi.int RI Ali, Mohammad/E-2365-2017 OI Ali, Mohammad/0000-0003-1410-388X NR 28 TC 54 Z9 56 U1 1 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2334 J9 BMC INFECT DIS JI BMC Infect. Dis. PD OCT 20 PY 2005 VL 5 AR 89 DI 10.1186/1471-2334-5-89 PG 11 WC Infectious Diseases SC Infectious Diseases GA 979ZA UT WOS:000232982500001 PM 16242013 ER PT J AU Kim, SA Jacobson, KA Kim, HS AF Kim, SA Jacobson, KA Kim, HS TI New synthetic approach to the bicyclo[3.1.0]hexane ring system from (+)-(1R,4R)-4-(benzyloxymethyl)-4-(hydroxymethyl)cyclopent-2-enol SO BULLETIN OF THE KOREAN CHEMICAL SOCIETY LA English DT Article DE bicyclo[3.1.0]hexane; northern nucleoside; adenosine receptor agonists; antagonists ID (CYTOSINE C5)-METHYLTRANSFERASE; BIOLOGICAL-ACTIVITY; ANALOGS; NUCLEOSIDES; POTENT; OLIGONUCLEOTIDES C1 Wonkwang Univ, Coll Pharm, Iksan 570749, Jeonbuk, South Korea. NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Kim, HS (reprint author), Wonkwang Univ, Coll Pharm, Iksan 570749, Jeonbuk, South Korea. EM hankidad@wonkwang.ac.kr RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 NR 18 TC 2 Z9 2 U1 0 U2 2 PU KOREAN CHEMICAL SOC PI SEOUL PA 635-4 YEOGSAM-DONG, KANGNAM-GU, SEOUL 135-703, SOUTH KOREA SN 0253-2964 J9 B KOR CHEM SOC JI Bull. Korean Chem. Soc. PD OCT 20 PY 2005 VL 26 IS 10 BP 1503 EP 1504 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 983DS UT WOS:000233211900008 ER PT J AU Warren, KE Aikin, AA Libucha, M Widemann, BC Fox, E Packer, RJ Balis, FM AF Warren, KE Aikin, AA Libucha, M Widemann, BC Fox, E Packer, RJ Balis, FM TI Phase I study of O-6-benzylguanine and temozolomide administered daily for 5 days to pediatric patients with solid tumors SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 8th Annual Meeting of the Society-for-Neuro-Oncology CY NOV 13-16, 2003 CL Keystone, CO SP Soc Neuro Oncol ID O-6-ALKYLGUANINE-DNA ALKYLTRANSFERASE ACTIVITY; ANTITUMOR IMIDAZOTETRAZINES; GLIOBLASTOMA-MULTIFORME; DNA-REPAIR; O6-ALKYLGUANINE-DNA ALKYLTRANSFERASE; MALIGNANT GLIOMA; MISMATCH REPAIR; ADVANCED CANCER; BRAIN-TUMORS; 1ST RELAPSE AB Purpose This pediatric phase I trial of O-6-benzylguanine (O(6)BG) and temozolomide (TMZ) on a daily schedule for 5 days, every 28 days was performed to determine the maximum-tolerated dose of TMZ when given with a biologically active dose of O(6)BG and to define the toxicity profile of the combination in children with solid tumors. Patients and Methods Patients <= 21 years old with refractory solid tumors were eligible. O(6)BG was administered intravenously over 60 minutes daily for 5 days. TMZ was administered orally 30 minutes after completion of each O(6)BG infusion. Starting doses of O(6)BG and TMZ were 60 mg/m(2)/d and 28 mg/m(2)/d, respectively. O(6)BG was escalated to 90 and 120 mg/m(2)/d; TMZ was subsequently escalated to 40, 55, 75, and 100 mg/m(2)/d. Cycles were repeated every 28 days. Results Forty-one patients were enrolled; 32 patients were assessable for toxicity. The combination of O(6)BG and TMZ was tolerable at TMZ doses less than half of the conventional dose of 200 mg/m(2)/d. Myelosuppression occurred sporadically at all dose levels and was the dose-limiting toxicity (DLT) at 100 mg/m(2)/d of TMZ combined with 120 mg/m2/d O(6)BG. Nonhematologic toxicities were generally mild. Evidence of antitumor activity was observed at 120 mg/ O(6)BG combined with TMZ doses of 55 mg/m(2)/d and above. Conclusion The recommended doses of O'BG administered with TMZ on a 5-day schedule in children are 120 mg/m(2)/d of O(6)BG and 75 mg/m(2)/d of TMZ. Evidence of activity was observed at these doses. Myelosuppression was the DLT. C1 Natl Canc Inst, Neurooncol Branch, Bethesda, MD 20892 USA. RP Warren, KE (reprint author), Natl Canc Inst, Neurooncol Branch, Bldg 82,Room 219,9030 Old Georgetown Rd, Bethesda, MD 20892 USA. EM warrenk@mail.nih.gov NR 50 TC 35 Z9 35 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD OCT 20 PY 2005 VL 23 IS 30 BP 7646 EP 7653 DI 10.1200/JCO.2005.02.0024 PG 8 WC Oncology SC Oncology GA 979IJ UT WOS:000232935300039 PM 16234526 ER PT J AU Blaney, SM Berg, SL Balis, F Poplack, D AF Blaney, SM Berg, SL Balis, F Poplack, D TI Mafosfamide: A new intra-CSF chemotherapy? Reply SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter C1 Baylor Coll Med, Texas Childrens Canc Ctr, Houston, TX 77030 USA. NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. Baylor Coll Med, Texas Childrens Canc Ctr, Houston, TX 77030 USA. RP Blaney, SM (reprint author), Baylor Coll Med, Texas Childrens Canc Ctr, Houston, TX 77030 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD OCT 20 PY 2005 VL 23 IS 30 BP 7749 EP 7749 DI 10.1200/JCO.2005.02.8803 PG 1 WC Oncology SC Oncology GA 979IJ UT WOS:000232935300056 ER PT J AU de Jong, FA Engels, FK Mathijssen, RHJ van Zuylen, L Verweij, J Peters, RPH Sparreboom, A AF de Jong, FA Engels, FK Mathijssen, RHJ van Zuylen, L Verweij, J Peters, RPH Sparreboom, A TI Medicinal cannabis in oncology practice: Still a bridge too far? Reply SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter C1 Erasmus Univ, Med Ctr, Dr Daniel Denhoed Canc Ctr, Dept Med Oncol, Rotterdam, Netherlands. Vrije Univ Amsterdam, Dept Internal Med, Med Ctr, NL-1081 HV Amsterdam, Netherlands. NCI, Clin Pharmacol Res Core, Bethesda, MD 20892 USA. RP de Jong, FA (reprint author), Erasmus Univ, Med Ctr, Dr Daniel Denhoed Canc Ctr, Dept Med Oncol, Rotterdam, Netherlands. RI Sparreboom, Alex/B-3247-2008; de Jong, Floris/F-5486-2011 NR 4 TC 1 Z9 1 U1 0 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD OCT 20 PY 2005 VL 23 IS 30 BP 7756 EP 7756 DI 10.1200/JCO.2005.02.7672 PG 1 WC Oncology SC Oncology GA 979IJ UT WOS:000232935300064 ER PT J AU Salganik, MP Hardie, DL Swart, B Dandie, GW Zola, H Shaw, S Shapiro, H Tinckam, K Milford, EL Wand, MP AF Salganik, MP Hardie, DL Swart, B Dandie, GW Zola, H Shaw, S Shapiro, H Tinckam, K Milford, EL Wand, MP TI Detecting antibodies with similar reactivity patterns in the HLDA8 blind panel of flow cytometry data SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Article; Proceedings Paper CT 8th International Workshop on Human Leucocyte Differentiation Antigens CY 2004 CL Adelaide, AUSTRALIA DE antibodies; classification; cluster of differentiation; CD; flow cytometry; blind panel; reactivity pattern; kernel smoothing AB The blind panel collected for the 8th Human Leucocyte Differentiation Antigens Workshop (HLDA8; http://www.hlda8.org) included 49 antibodies of known CD specificities and 76 antibodies of unknown specificity. We have identified groups of antibodies. showing similar patterns of reactivity that need to be investigated by biochemical methods to evaluate whether the antibodies within these groups are reacting with the same molecule. Our approach to data analysis was based on the work of Salganik et al. (in press) [Salganik, M.P., Milford E.L., Hardie D.L., Shaw, S., Wand, M.P., in press. Classifying antibodies using flow cytometry data: class prediction and class discovery. Biometrical Journal]. (c) 2005 Elsevier B.V. All rights reserved. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Univ Birmingham, Inst Biomed Res, MRC, Ctr Immune Regulat, Birmingham B15 2TT, W Midlands, England. Womens & Childrens Hosp, Child Hlth Res Inst, Adelaide, SA 5006, Australia. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. Ctr Microbial Cytometry, W Newton, MA 02465 USA. Harvard Univ, Sch Med, Dept Med, Brigham & Womens Hosp, Boston, MA 02115 USA. Univ New S Wales, Sch Math, Dept Stat, Sydney, NSW 2052, Australia. RP Salganik, MP (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, 665 Huntington Ave, Boston, MA 02115 USA. EM salganik@hsph.harvard.edu RI Wand, Matt /F-9413-2012; OI Wand, Matt /0000-0003-2555-896X; Tinckam, Kathryn/0000-0002-6638-2887 NR 17 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD OCT 20 PY 2005 VL 305 IS 1 BP 67 EP 74 DI 10.1016/j.jim.2005.07.002 PG 8 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 977OZ UT WOS:000232814400009 PM 16129446 ER PT J AU Kondrashov, AS AF Kondrashov, AS TI Evolutionary biology - Fruitfly genome is not junk SO NATURE LA English DT Editorial Material ID DROSOPHILA-MELANOGASTER; TRANSPOSABLE ELEMENTS; INTERGENIC REGIONS; MOUSE; PSEUDOGENES; SEQUENCES C1 NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Kondrashov, AS (reprint author), NIH, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. EM kondrashov@ncbi.nlm.nih.gov NR 16 TC 11 Z9 12 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD OCT 20 PY 2005 VL 437 IS 7062 BP 1106 EP 1106 DI 10.1038/4371106a PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 975KD UT WOS:000232660500031 PM 16237433 ER PT J AU Ghedin, E Sengamalay, NA Shumway, M Zaborsky, J Feldblyum, T Subbu, V Spiro, DJ Sitz, J Koo, H Bolotov, P Dernovoy, D Tatusova, T Bao, YM St George, K Taylor, J Lipman, DJ Fraser, CM Taubenberger, JK Salzberg, SL AF Ghedin, E Sengamalay, NA Shumway, M Zaborsky, J Feldblyum, T Subbu, V Spiro, DJ Sitz, J Koo, H Bolotov, P Dernovoy, D Tatusova, T Bao, YM St George, K Taylor, J Lipman, DJ Fraser, CM Taubenberger, JK Salzberg, SL TI Large-scale sequencing of human influenza reveals the dynamic nature of viral genome evolution SO NATURE LA English DT Article ID VIRUS NEURAMINIDASE; ANTIGENIC SITES; REASSORTMENT; PROTEIN; HOSPITALIZATIONS; PB1-F2; ASIA AB Influenza viruses are remarkably adept at surviving in the human population over a long timescale. The human influenza A virus continues to thrive even among populations with widespread access to vaccines, and continues to be a major cause of morbidity and mortality(1,2). The virus mutates from year to year, making the existing vaccines ineffective on a regular basis, and requiring that new strains be chosen for a new vaccine. Less-frequent major changes, known as antigenic shift, create new strains against which the human population has little protective immunity, thereby causing worldwide pandemics. The most recent pandemics include the 1918 'Spanish' flu, one of the most deadly outbreaks in recorded history, which killed 30-50 million people worldwide, the 1957 'Asian' flu, and the 1968 'Hong Kong' flu(3). Motivated by the need for a better understanding of influenza evolution, we have developed flexible protocols that make it possible to apply large-scale sequencing techniques to the highly variable influenza genome. Here we report the results of sequencing 209 complete genomes of the human influenza A virus, encompassing a total of 2,821,103 nucleotides. In addition to increasing markedly the number of publicly available, complete influenza virus genomes, we have discovered several anomalies in these first 209 genomes that demonstrate the dynamic nature of influenza transmission and evolution. This new, large-scale sequencing effort promises to provide a more comprehensive picture of the evolution of influenza viruses and of their pattern of transmission through human and animal populations. All data from this project are being deposited, without delay, in public archives. C1 Inst Genom Res, Rockville, MD 20850 USA. NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. New York State Dept Hlth, Wadsworth Ctr Labs & Res, Albany, NY 12201 USA. Armed Forces Inst Pathol, Dept Mol Pathol, Rockville, MD 20850 USA. Univ Maryland, Inst Adv Comp Studies, Ctr Bioinformat & Computat Biol, College Pk, MD 20742 USA. RP Salzberg, SL (reprint author), Inst Genom Res, 9712 Med Ctr Dr, Rockville, MD 20850 USA. EM salzberg@umd.edu RI Salzberg, Steven/F-6162-2011; OI Salzberg, Steven/0000-0002-8859-7432; Fraser, Claire/0000-0003-1462-2428 NR 27 TC 277 Z9 293 U1 7 U2 62 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD OCT 20 PY 2005 VL 437 IS 7062 BP 1162 EP 1166 DI 10.1038/nature04239 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 975KD UT WOS:000232660500046 PM 16208317 ER PT J AU Romond, EH Perez, EA Bryant, J Suman, VJ Geyer, CE Davidson, NE Tan-Chiu, E Martino, S Paik, S Kaufman, PA Swain, SM Pisansky, TM Fehrenbacher, L Kutteh, LA Vogel, VG Visscher, DW Yothers, G Jenkins, RB Brown, AM Dakhil, SR Mamounas, EP Lingle, WL Klein, PM Ingle, JN Wolmark, N AF Romond, EH Perez, EA Bryant, J Suman, VJ Geyer, CE Davidson, NE Tan-Chiu, E Martino, S Paik, S Kaufman, PA Swain, SM Pisansky, TM Fehrenbacher, L Kutteh, LA Vogel, VG Visscher, DW Yothers, G Jenkins, RB Brown, AM Dakhil, SR Mamounas, EP Lingle, WL Klein, PM Ingle, JN Wolmark, N TI Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID METASTASES; TRIAL; WOMEN; HER2 AB BACKGROUND: We present the combined results of two trials that compared adjuvant chemotherapy with or without concurrent trastuzumab in women with surgically removed HER2-positive breast cancer. METHODS: The National Surgical Adjuvant Breast and Bowel Project trial B-31 compared doxorubicin and cyclophosphamide followed by paclitaxel every 3 weeks (group 1) with the same regimen plus 52 weeks of trastuzumab beginning with the first dose of paclitaxel (group 2). The North Central Cancer Treatment Group trial N9831 compared three regimens: doxorubicin and cyclophosphamide followed by weekly paclitaxel (group A), the same regimen followed by 52 weeks of trastuzumab after paclitaxel (group B), and the same regimen plus 52 weeks of trastuzumab initiated concomitantly with paclitaxel (group C). The studies were amended to include a joint analysis comparing groups 1 and A (the control group) with groups 2 and C (the trastuzumab group). Group B was excluded because trastuzumab was not given concurrently with paclitaxel. RESULTS: By March 15, 2005, 394 events (recurrent, second primary cancer, or death before recurrence) had been reported, triggering the first scheduled interim analysis. Of these, 133 were in the trastuzumab group and 261 in the control group (hazard ratio, 0.48; P<0.0001). This result crossed the early stopping boundary. The absolute difference in disease-free survival between the trastuzumab group and the control group was 12 percent at three years. Trastuzumab therapy was associated with a 33 percent reduction in the risk of death (P=0.015). The three-year cumulative incidence of class III or IV congestive heart failure or death from cardiac causes in the trastuzumab group was 4.1 percent in trial B-31 and 2.9 percent in trial N9831. CONCLUSIONS: Trastuzumab combined with paclitaxel after doxorubicin and cyclophosphamide improves outcomes among women with surgically removed HER2-positive breast cancer. C1 Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA. Univ Kentucky, Lexington, KY USA. N Cent Canc Treatment Grp, Rochester, MN USA. Mayo Clin Jacksonville, Jacksonville, FL 32224 USA. Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. Mayo Clin, Rochester, MN USA. Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Canc Res Network, Plantation, FL USA. Angeles Clin & Res Inst, Santa Monica, CA USA. Dartmouth Hitchcock Med Ctr, Norris Cotton Canc Ctr, Lebanon, NH 03766 USA. NCI, Canc Therapeut Branch, Bethesda, MD 20892 USA. Kaiser Permanente Med Ctr No Calif, Vallejo, CA USA. Oncol Associates Cedar Rapids, Cedar Rapids, IA USA. Wichita Community Clin Oncol Program, Wichita, KS USA. Aultman Hlth Fdn, Canton, OH USA. Genentech Inc, San Francisco, CA USA. RP Geyer, CE (reprint author), Allegheny Canc Ctr, 5th Fl,320 E North Ave, Pittsburgh, PA 15212 USA. EM cgeyer@wpahs.org RI Tang, Amy/L-3226-2016; OI Tang, Amy/0000-0002-5772-2878; Yothers, Greg/0000-0002-7965-7333 FU NCI NIH HHS [U10-CA-021115, U10-CA-12027, U10-CA-25224, U10-CA-31946, U10-CA-32102, U10-CA-37377, U10-CA-69651, U10-CA-69974] NR 17 TC 2940 Z9 3058 U1 42 U2 212 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 20 PY 2005 VL 353 IS 16 BP 1673 EP 1684 DI 10.1056/NEJMoa052122 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 975IC UT WOS:000232653200007 PM 16236738 ER PT J AU Rhen, T Cidlowski, JA AF Rhen, T Cidlowski, JA TI Antiinflammatory action of glucocorticoids - New mechanisms for old drugs SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID FACTOR-KAPPA-B; LIGAND-BINDING DOMAIN; MESSENGER-RNA; UNITED-STATES; RECEPTOR-BETA; CORTICOSTEROID RESISTANCE; INFLAMMATORY RESPONSE; RHEUMATOID-ARTHRITIS; MEDIATED INHIBITION; AUTOIMMUNE-DISEASES C1 NIEHS, Lab Signal Transduct, Res Triangle Pk, NC 27709 USA. Univ N Dakota, Dept Biol, Grand Forks, ND 58202 USA. NIH, US Dept HHS, Bethesda, MD 20892 USA. RP Cidlowski, JA (reprint author), NIEHS, Lab Signal Transduct, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM cidlows1@niehs.rlh.gov NR 92 TC 1103 Z9 1170 U1 13 U2 109 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 20 PY 2005 VL 353 IS 16 BP 1711 EP 1723 DI 10.1056/NEJMra050541 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA 975IC UT WOS:000232653200011 PM 16236742 ER PT J AU Papoutsaki, M Moretti, F Lanza, M Marinari, B Sartorelli, V Guerrini, L Chimenti, S Levrero, M Costanzo, A AF Papoutsaki, M Moretti, F Lanza, M Marinari, B Sartorelli, V Guerrini, L Chimenti, S Levrero, M Costanzo, A TI A p38-dependent pathway regulates Delta Np63 DNA binding to p53-dependent promoters in UV-induced apoptosis of keratinocytes SO ONCOGENE LA English DT Article DE p53; p63; apoptosis; p38; keratinocytes ID JUN NH2-TERMINAL KINASE; P53; P63; PHOSPHORYLATION; STRESS; IRRADIATION; ACTIVATION; EXPRESSION; MUTATIONS; CARCINOMA AB The p53 protein plays a pivotal role in determining the quality of the response to DNA damage through its transcriptional activity. Upon DNA damage, p53 is activated by post-translational modi. cations, binds its cognate sequences on the promoters of its target genes and stimulates transcription. In proliferating keratinocytes, the activity of p53 is blunted by its inhibitor Delta Np63 alpha. Here, we describe a novel mechanism through which Delta Np63 functions in order to prevent the survival and propagation of ultraviolet (UV)-damaged keratinocytes. We found that UVB stimulation induces the rapid phosphorylation of DNp63, which precedes DNp63 transcriptional downregulation and protein degradation, which is mediated by the p38 MAPK. Phosphorylated Delta Np63 has a lower affinity for p53REs and detaches from cell cycle arrest and apoptotic promoters, thus allowing the rapid activation of p53-dependent transcriptional apoptotic program. C1 Univ Roma Tor Vergata, Dept Dermatol, Dermatol Clin, I-00133 Rome, Italy. CRS Regina Elena Canc Ctr, Fondaz A Cesalpino, I-00153 Rome, Italy. NIMAS, Muscle Biol Lab, Muscle Gene Express Grp, NIH, Bethesda, MD USA. Univ Milan, Dipartimento Genet & Biol Microorganismi, I-20122 Milan, Italy. Univ Roma La Sapienza, Dept Internal Med, Rome, Italy. RP Levrero, M (reprint author), Univ Roma Tor Vergata, Dept Dermatol, Dermatol Clin, Viale Oxford 81, I-00133 Rome, Italy. EM levmax@tin.it; antonio.costanzo@uniroma2.it RI Costanzo, Antonio/D-3896-2012; OI Costanzo, Antonio/0000-0001-9697-2557 FU Telethon [E.1325] NR 27 TC 33 Z9 34 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD OCT 20 PY 2005 VL 24 IS 46 BP 6970 EP 6975 DI 10.1038/sj.onc.1208835 PG 6 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 975ZD UT WOS:000232701700011 PM 16007154 ER PT J AU Fekete, CA Applefield, DJ Blakely, SA Shirokikh, N Pestova, T Lorsch, JR Hinnebusch, AG AF Fekete, CA Applefield, DJ Blakely, SA Shirokikh, N Pestova, T Lorsch, JR Hinnebusch, AG TI The eIF1A C-terminal domain promotes initiation complex assembly, scanning and AUG selection in vivo SO EMBO JOURNAL LA English DT Article DE eIF1A; eIF2; GCN4; scanning; translation ID GCN4 TRANSLATIONAL CONTROL; EUKARYOTIC TRANSLATION; PREINITIATION COMPLEX; SACCHAROMYCES-CEREVISIAE; START CODON; MULTIFACTOR COMPLEX; RIBOSOMAL-SUBUNIT; MEDIATE BINDING; YEAST; RECOGNITION AB Translation initiation factor 1A stimulates 40S-binding of the eukaryotic initiation factor 2 (eIF2)/GTP/Met-tRNA(i)(Met) ternary complex (TC) and promotes scanning in vitro. eIF1A contains an OB-fold present in bacterial IF1 plus N- and C-terminal extensions. Truncating the C-terminus (DC) or mutating OB-fold residues (66-70) of eIF1A reduced general translation in vivo but increased GCN4 translation (Gcd(-) phenotype) in a manner suppressed by overexpressing TC. Consistent with this, both mutations diminished 40S-bound TC, eIF5 and eIF3 in vivo, and DC impaired TC recruitment in vitro. The assembly defects of the OB-fold mutation can be attributed to reduced 40S-binding of eIF1A, whereas DC impairs eIF1A function on the ribosome. A substitution in the C-terminal helix (98-101) also reduced 43S assembly in vivo. Rather than producing a Gcd(-) phenotype, however, 98-101 impairs GCN4 derepression in a manner consistent with defective scanning by reinitiating ribosomes. Indeed, 98-101 allows formation of aberrant 48S complexes in vitro and increases utilization of non-AUG codons in vivo. Thus, the OB-fold is crucial for ribosome-binding and the C-terminal domain of eIF1A has eukaryotic-specific functions in TC recruitment and scanning. C1 NICHHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Biophys & Biophys Chem, Baltimore, MD 21205 USA. SUNY Hlth Sci Ctr, Dept Microbiol & Immunol, Brooklyn, NY 11203 USA. RP Hinnebusch, AG (reprint author), NICHHD, Lab Gene Regulat & Dev, NIH, Bldg 6A,Room B1A-13, Bethesda, MD 20892 USA. EM ahinnebusch@nih.gov OI Shirokikh, Nikolay/0000-0001-8249-358X; Lorsch, Jon/0000-0002-4521-4999 NR 44 TC 54 Z9 55 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 0261-4189 J9 EMBO J JI Embo J. PD OCT 19 PY 2005 VL 24 IS 20 BP 3588 EP 3601 DI 10.1038/sj.emboj.7600821 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 981WJ UT WOS:000233118400007 PM 16193068 ER PT J AU Hampson, LA Emanuel, EJ AF Hampson, LA Emanuel, EJ TI Physicians advising investment firms SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 NIH, Dept Clin Bioeth, Ctr Clin, Bethesda, MD 20892 USA. RP Hampson, LA (reprint author), NIH, Dept Clin Bioeth, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. EM lhampson@cc.nih.gov NR 5 TC 1 Z9 1 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD OCT 19 PY 2005 VL 294 IS 15 BP 1897 EP 1897 DI 10.1001/jama.294.15.1897-b PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 974OZ UT WOS:000232602600014 PM 16234491 ER PT J AU Chen, HM Puhl, HL Niu, SL Mitchell, DC Ikeda, SR AF Chen, HM Puhl, HL Niu, SL Mitchell, DC Ikeda, SR TI Expression of Rem2, an RGK family small GTPase, reduces N-type calcium current without affecting channel surface density SO JOURNAL OF NEUROSCIENCE LA English DT Article DE channel; sympathetic; dorsal root ganglion; Rem2; small GTPase; conotoxin ID ALPHA(1)-BETA SUBUNIT INTERACTION; VOLTAGE-DEPENDENT MODULATION; RAT SYMPATHETIC NEURONS; G-PROTEIN; BETA-SUBUNIT; CA2+ CHANNELS; PERIPHERAL NEURONS; INTERACTION DOMAIN; MEMBER; GEM AB Rad, Gem/Kir, Rem, and Rem2 are members of the Ras-related RGK (Rad, Gem, and Kir) family of small GTP-binding proteins. Heterologous expression of RGK proteins interferes with de novo calcium channel assembly/trafficking and dramatically decreases the amplitude of currents arising from preexisting high-voltage-activated calcium channels. These effects probably result from the direct interaction of RGK proteins with calcium channel beta subunits. Among the RGK family, Rem2 is the only member abundantly expressed in neuronal tissues. Here, we examined the ability of Rem2 to modulate endogenous voltage-activated calcium channels in rat sympathetic and dorsal root ganglion neurons. Heterologous expression of Rem2 nearly abolished calcium currents arising from preexisting high-voltage-activated calcium channels without affecting low-voltage-activated calcium channels. Rem2 inhibition of N-type calcium channels required both the Ras homology (core) domain and the polybasic C terminus. Mutation of a putative GTP/Mg2+ binding motif in Rem2 did not affect suppression of calcium currents. Loading neurons with GDP-beta-S via the patch pipette did not reverse Rem2mediated calcium channel inhibition. Finally, [I-125] Tyr(22)-omega-conotoxin GVIA cell surface binding in tsA201 cells stably expressing N- type calcium channels was not altered by Rem2 expression at a time when calcium current was totally abolished. Together, our results support a model in which Rem2 localizes to the plasma membrane via a C- erminal polybasic motif and interacts with calcium channel beta subunits in the preassembled N- type channel, thereby forming a nonconducting species. C1 NIAAA, Lab Mol Physiol, NIH, Bethesda, MD 20892 USA. NIAAA, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD 20892 USA. RP Ikeda, SR (reprint author), NIAAA, Lab Mol Physiol, NIH, Fishers Lane 5625,Room TS11,MSC9411, Bethesda, MD 20892 USA. EM sikeda@mail.nih.gov OI Ikeda, Stephen/0000-0002-4088-9508; Puhl, Henry/0000-0003-3095-7201 FU Intramural NIH HHS NR 52 TC 63 Z9 64 U1 4 U2 23 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD OCT 19 PY 2005 VL 25 IS 42 BP 9762 EP 9772 DI 10.1523/JNEUROSCI.3111-05.2005 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 975NN UT WOS:000232669300021 PM 16237180 ER PT J AU Showalter, BM Reynolds, MM Valdez, CA Saavedra, JE Davies, KM Klose, JR Chmurny, GN Citro, ML Barchi, JJ Merz, SI Meyerhoff, ME Keefer, LK AF Showalter, BM Reynolds, MM Valdez, CA Saavedra, JE Davies, KM Klose, JR Chmurny, GN Citro, ML Barchi, JJ Merz, SI Meyerhoff, ME Keefer, LK TI Diazeniumdiolate ions as leaving groups in anomeric displacement reactions: A protection-deprotection strategy for ionic diazeniumdiolates SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID NITRIC-OXIDE DONORS C1 Natl Canc Inst, Chem Sect, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. Univ Michigan, Dept Chem, Ann Arbor, MI 48109 USA. SAIC Frederick Inc, Natl Canc Inst, Basic Res Program, Frederick, MD 21702 USA. George Mason Univ, Dept Chem, Fairfax, VA 22030 USA. SAIC Frederick Inc, Lab Proteom & Analyt Technol, Natl Canc Inst, Frederick, MD 21702 USA. Natl Canc Inst, Med Chem Lab, Frederick, MD 21702 USA. Michigan Crit Care Consultants Inc, Ann Arbor, MI 48103 USA. RP Keefer, LK (reprint author), Natl Canc Inst, Chem Sect, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. EM keefer@ncifcrf.gov RI Barchi Jr., Joseph/N-3784-2014; Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 FU NCI NIH HHS [N01 CO 12400] NR 10 TC 18 Z9 18 U1 1 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD OCT 19 PY 2005 VL 127 IS 41 BP 14188 EP 14189 DI 10.1021/ja054510a PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 974QD UT WOS:000232605600034 PM 16218605 ER PT J AU Goldstein, AM Tucker, MA AF Goldstein, AM Tucker, MA TI A piece of the melanoma puzzle SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID CDKN2A MUTATIONS; PRONE FAMILIES; ESTIMATING PENETRANCE; KIN-COHORT; RISK; GENETICS; HISTORY C1 NCI, NIH, DHHS, Genet Epidemiol Branch,Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Goldstein, AM (reprint author), NCI, NIH, DHHS, Genet Epidemiol Branch,Div Canc Epidemiol & Genet, Execut Plaza S,Rm 7004,6120 Execut Blvd,MSC 7236, Bethesda, MD 20892 USA. EM goldstea@exchange.nih.gov RI Tucker, Margaret/B-4297-2015 FU Intramural NIH HHS NR 17 TC 2 Z9 2 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD OCT 19 PY 2005 VL 97 IS 20 BP 1486 EP 1487 DI 10.1093/jnci/dji359 PG 2 WC Oncology SC Oncology GA 979OA UT WOS:000232953500001 PM 16234555 ER PT J AU McNutt, MC Tongbai, R Cui, WW Collins, I Freebern, WJ Montano, I Haggerty, CM Chandramouli, GVR Gardner, K AF McNutt, MC Tongbai, R Cui, WW Collins, I Freebern, WJ Montano, I Haggerty, CM Chandramouli, GVR Gardner, K TI Human promoter genomic composition demonstrates non-random groupings that reflect general cellular function SO BMC BIOINFORMATICS LA English DT Article ID FACTOR-BINDING SITES; TRANSCRIPTION FACTOR; INTERLEUKIN-2 PROMOTER; VERTEBRATE GENOMES; CORE PROMOTER; IL-2 PROMOTER; START SITES; CPG ISLANDS; EXPRESSION; ACTIVATION AB Background: The purpose of this study is to determine whether or not there exists nonrandom grouping of cis-regulatory elements within gene promoters that can be perceived independent of gene expression data and whether or not there is any correlation between this grouping and the biological function of the gene. Results: Using ProSpector, a web-based promoter search and annotation tool, we have applied an unbiased approach to analyze the transcription factor binding site frequencies of 1400 base pair genomic segments positioned at 1200 base pairs upstream and 200 base pairs downstream of the transcriptional start site of 7298 commonly studied human genes. Partitional clustering of the transcription factor binding site composition within these promoter segments reveals a small number of gene groups that are selectively enriched for gene ontology terms consistent with distinct aspects of cellular function. Significance ranking of the class-determining transcription factor binding sites within these clusters show substantial overlap between the gene ontology terms of the transcriptions factors associated with the binding sites and the gene ontology terms of the regulated genes within each group. Conclusion: Thus, gene sorting by promoter composition alone produces partitions in which the "regulated" and the "regulators" cosegregate into similar functional classes. These findings demonstrate that the transcription factor binding site composition is non-randomly distributed between gene promoters in a manner that reflects and partially defines general gene class function. C1 NCI, Ctr Adv Technol, Lab Receptor Biol & Gene Express, Bethesda, MD 20892 USA. Univ Texas, SW Med Ctr Dallas, Dallas, TX 75235 USA. Bristol Myers Squibb Co, Syracuse, NY USA. RP Gardner, K (reprint author), NCI, Ctr Adv Technol, Lab Receptor Biol & Gene Express, Bethesda, MD 20892 USA. EM markey.mcnutt@utsouthwestern.edu; tongbair@mail.nih.gov; cuiw@mail.nih.gov; collinsi@mail.nih.gov; freeberw@mail.nih.gov; montanoi@mail.nih.gov; haggertc@mail.nih.gov; chandrag@mail.nih.gov; gardnerk@mail.nih.gov FU Intramural NIH HHS NR 52 TC 5 Z9 5 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD OCT 18 PY 2005 VL 6 AR 259 DI 10.1186/1471-2105-6-259 PG 23 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 979DH UT WOS:000232922100001 PM 16232321 ER PT J AU Chen, QR Bilke, S Khan, J AF Chen, QR Bilke, S Khan, J TI High-resolution cDNA microarray-based comparative genomic hybridization analysis in neuroblastoma SO CANCER LETTERS LA English DT Article DE neuroblastoma; array CGH; microarray; tumor evolution; DNA copy number; genornic alteration; amplification; MYCN ID N-MYC AMPLIFICATION; COPY-NUMBER; ARRAY-CGH; CELL-LINES; BREAST-CANCER; DNA; TUMORS; GENE; DELETION; REVEALS AB Neuroblastoma (NB) is one of the most common pediatric solid tumors and displays a broad variety of genomic alterations. Array-based comparative genomic hybridization (A-CGH) is a novel technology enabling the high-resolution detection of DNA copy number aberrations. In this article, we outline features of this new technology and approaches of data analysis. We focus on stage specific DNA copy number variations in neuroblastoma detected by cDNA array-based comparative genomic hybridization (A-CGH). We also discuss hypothetic evolutionary models of neuroblastoma progression that can be derived from A-CGH data. Published by Elsevier Ireland Ltd. C1 NCI, Oncogenom Sect, Pediat Oncol Branch, Ctr Adv Technol, Gaithersburg, MD 20877 USA. RP Khan, J (reprint author), NCI, Oncogenom Sect, Pediat Oncol Branch, Ctr Adv Technol, 8717 Govt Circle, Gaithersburg, MD 20877 USA. EM chenqi@mail.nih.gov; bilkes@mail.nih.gov; khanjav@mail.nih.gov RI Khan, Javed/P-9157-2014 OI Khan, Javed/0000-0002-5858-0488 NR 50 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD OCT 18 PY 2005 VL 228 IS 1-2 BP 71 EP 81 DI 10.1016/j.canlet.2004.12.056 PG 11 WC Oncology SC Oncology GA 969NN UT WOS:000232241100012 PM 15951107 ER PT J AU Ganesh, SK Nabel, EG AF Ganesh, SK Nabel, EG TI Genomics of in-stent restenosis - Early insights into a complex disease SO CIRCULATION LA English DT Editorial Material DE editorials; atherosclerosis; genes; genetics; restenosis ID CORONARY-ARTERY-DISEASE; C-REACTIVE PROTEIN; INFLAMMATION; ATHEROSCLEROSIS C1 NHLBI, NIH, Bethesda, MD 20892 USA. RP Nabel, EG (reprint author), NHLBI, NIH, Bldg 31,Room 5A52,31 Ctr Dr, Bethesda, MD 20892 USA. EM enabel@nih.gov NR 9 TC 3 Z9 3 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 18 PY 2005 VL 112 IS 16 BP 2378 EP 2379 DI 10.1161/CIRCULATIONAHA.105.574780 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 974QR UT WOS:000232607000001 PM 16230493 ER PT J AU Dries, DL Victor, RG Rame, JE Cooper, RS Wu, XD Zhu, XF Leonard, D Ho, SI Wu, QY Post, W Drazner, MH AF Dries, DL Victor, RG Rame, JE Cooper, RS Wu, XD Zhu, XF Leonard, D Ho, SI Wu, QY Post, W Drazner, MH TI Corin gene minor allele defined by 2 missense mutations is common in blacks and associated with high blood pressure and hypertension SO CIRCULATION LA English DT Article DE atrial natriuretic factor; genes; genetics; hypertension; peptides ID PROATRIAL NATRIURETIC PEPTIDE; AFRICAN-AMERICANS; SERINE-PROTEASE; GENOMIC CONTROL; MOUSE MODELS; MICE LACKING; DISEASE; POPULATION; HEART; PREVALENCE AB Background - The natriuretic peptide system contributes to blood pressure regulation. Atrial and brain natriuretic peptides are cleaved into smaller biologically active molecules by corin, a transmembrane serine protease expressed in cardiomyocytes. Method and Results - This genotype-phenotype genetic association study included replication samples and genomic control to correct for population stratification. Sequencing of the human corin gene identified 2 nonsynonymous, nonconservative single nucleotide polymorphisms (Q568P and T555I) in near-complete linkage disequilibrium, thus describing a single minor I555 (P568) corin gene allele. This allele was present in the heterozygote state in approximate to 12% of blacks but was extremely rare in whites (< 0.5% were homozygous for the minor allele). In our primary population sample, the Dallas Heart Study, after adjustment for potential confounders, including population stratification, the corin I555 (P568) allele remained independently associated with increased risk for prevalent hypertension ( odds ratio, 1.63; 95% CI, 1.11 to 2.38; P = 0.013). The corin I555 ( P568) allele also was associated with higher systolic blood pressure in subjects not using antihypertensive medication in unadjusted (133.7 +/- 20.7 versus 129.4 +/- 17.4 mm Hg; P = 0.029) and adjusted (132.5 +/- 1.6 versus 128.9 +/- 0.6 mm Hg; P = 0.029) analyses. The independent association of the minor corin allele with increased risk for prevalent hypertension was confirmed in the Multi-Ethnic Study of Atherosclerosis ( odds ratio, 1.50; 95% CI, 1.09 to 2.06; P = 0.014). In addition, the association of the minor corin I555 ( P568) allele with higher systolic blood pressure was confirmed in adjusted analysis in the Chicago Genetics of Hypertension Study (125.8 +/- 1.9 versus 121.4 +/- 0.7 mm Hg; P = 0.03). Conclusions - The corin I555 ( P568) allele is common in blacks and is associated with higher blood pressure and an increased risk for prevalent hypertension. C1 Univ Texas, SW Med Ctr, Hypertens Div, Dallas, TX USA. Univ Texas, SW Med Ctr, Donald W Reynolds Cardiovasc Clin Res Ctr, Div Cardiol, Dallas, TX USA. Loyola Univ, Stritch Sch Med, Dept Prevent Med & Epidemiol, Maywood, IL 60153 USA. Johns Hopkins Univ Hosp, Donald W Reynolds Cardiovasc Clin Res Ctr, Baltimore, MD 21287 USA. Johns Hopkins Univ Hosp, Div Cardiol, Baltimore, MD 21287 USA. NHLBI, Cardiovasc Branch, Bethesda, MD 20892 USA. Berlex Biosci, Dept Cardiovasc Res, Richmond, CA USA. RP Dries, DL (reprint author), Hosp Univ Penn, Heart Failure Transplant Grp, 6 Penn Tower,3400 Spruce St, Philadelphia, PA 19104 USA. EM daniel.dries@uphs.upenn.edu FU NHLBI NIH HHS [K23-HL04455]; PHS HHS [47910, R0-1 45508] NR 43 TC 107 Z9 114 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 18 PY 2005 VL 112 IS 16 BP 2403 EP 2410 DI 10.1161/CIRCULATIONAHA.105.568881 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 974QR UT WOS:000232607000006 PM 16216958 ER PT J AU Karginov, VA Nestorovich, EM Moayeri, M Leppla, SH Bezrukov, SM AF Karginov, VA Nestorovich, EM Moayeri, M Leppla, SH Bezrukov, SM TI Blocking anthrax lethal toxin at the protective antigen channel by using structure-inspired drug design SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE infectious diseases; membrane transport; modified cyclodextrins ID SYMMETRICAL TETRAALKYLAMMONIUM IONS; PHOSPHOLIPID-BILAYER MEMBRANES; VOLTAGE-DEPENDENT BLOCK; PLANAR LIPID-BILAYERS; BACILLUS-ANTHRACIS; CYCLODEXTRINS; MICROBIOLOGY; PROTEIN AB Bacillus anthracis secretes three polypepticles: protective antigen (PA), lethal factor (LF), and edema factor (EF), which interact at the surface of mammalian cells to form toxic complexes. LF and EF are enzymes that target substrates within the cytosol; PA provides a heptameric pore to facilitate LF and EF transport into the cytosol. Other than administration of antibiotics shortly after exposure, there is currently no approved effective treatment for inhalational anthrax. Here we demonstrate an approach to disabling the toxin: high-affinity blockage of the PA pore by a rationally designed low-molecular weight compound that prevents LF and EF entry into cells. Guided by the sevenfold symmetry and predominantly negative charge of the PA pore, we synthesized small cyclic molecules of sevenfold symmetry, beta-cyclodextrins chemically modified to add seven positive charges. By channel reconstitution and high-resolution conductance recording, we show that per-6-(3-aminopropylthio)-beta-cyclodextrin interacts strongly with the PA pore lumen, blocking PA-induced transport at subnanomolar concentrations (in 0.1 M KCl). The compound protected RAW 264.7 mouse macrophages from cytotoxicity of anthrax lethal toxin (= PA + LF). More importantly, it completely protected the highly susceptible Fischer F344 rats from lethal toxin. We anticipate that this approach will serve as the basis for a structure-directed drug discovery program to find new and effective treatments for anthrax. C1 NICHHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. Innovat Biol Inc, Manassas, VA 20110 USA. NIAID, Bacterial Toxins & Therapeut Sect, NIH, Bethesda, MD 20892 USA. RP Bezrukov, SM (reprint author), NICHHD, Lab Phys & Struct Biol, NIH, 9000 Rockville Pike,Bldg 9,Room 1N-124B, Bethesda, MD 20892 USA. EM bezrukos@mail.nih.gov FU Intramural NIH HHS; NIAID NIH HHS [1R43AI052894-01, R43 AI052894] NR 31 TC 86 Z9 86 U1 3 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 18 PY 2005 VL 102 IS 42 BP 15075 EP 15080 DI 10.1073/pnas.0507488102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 977NZ UT WOS:000232811800026 PM 16214885 ER PT J AU Wakabayashi, Y Dutt, P Lippincott-Schwartz, J Arias, IM AF Wakabayashi, Y Dutt, P Lippincott-Schwartz, J Arias, IM TI Rab11a and myosin Vb are required for bile canalicular formation in WIF-B9 cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE hepatocyte polarization; plasma membrane segregation ID POLARIZED HEPATIC CELLS; CONJUGATE EXPORT PUMP; CANINE KIDNEY-CELLS; MEMBRANE TRAFFICKING; ABC TRANSPORTERS; APICAL DOMAIN; B CELLS; PROTEINS; LIVER; ACCUMULATION AB Hepatocytes polarize by forming functionally distinct sinusoidal (basolateral) and canalicular (apical) plasma membrane domains. Two distinct routes are used for delivery of membrane proteins to the canaliculus. Proteins having glycosylphosphatidylinositol anchors or single transmembrane domains are targeted to the sinusoical plasma membrane from where they transcytose to the canalicular domain. In contrast, apical ATP-bincling-cassette (ABC) transporters, which are required for energy-dependent biliary secretion of bile acids (ABCB11), phospholipids (ABCB4), and non-bile acid organic anions (ABCC2), lack initial residence in the basolateral plasma membrane and traffic directly from Golgi membranes to the canalicular membrane. While investigating mechanisms of apical targeting in WIF-B9 cells, a polarized hepatic epithelial cell line, we observed that rab11a is required for canalicular formation. Knockdown of rab11a or overexpression of the rab11a-GDP locked form prevented canalicular formation as did overexpression of the myosin Vb motorless tail domain. In WIF-B9 cells, which lack bile canaliculi, apical ABC transporters colocalized with transcytotic membrane proteins in rab11a-containing endosomes and, unlike the transcytotic markers, did not distribute to the plasma membrane. We propose that polarization of hepatocytes (i.e., canalicular biogenesis) requires recruitment of rab11a and myosin Vb to intracellular membranes that contain apical ABC transporters and transcytotic markers, permitting their targeting to the plasma membrane. In this model, polarization is initiated upon delivery of rab11a-myosin Vb-containing membranes to the surface, which causes plasma membrane at the site of delivery to differentiate into apical domain (bile canaliculus). C1 NICHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. Tufts Univ, Sch Med, Dept Physiol, Boston, MA 02111 USA. RP Arias, IM (reprint author), NICHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. EM ariasi@mail.nih.gov FU NIDDK NIH HHS [R01 DK035652, DK-35652, DK-54785, R01 DK054785] NR 35 TC 72 Z9 73 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 18 PY 2005 VL 102 IS 42 BP 15087 EP 15092 DI 10.1073/pnas.0503702102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 977NZ UT WOS:000232811800028 PM 16214890 ER PT J AU Nakatani, Y Konishi, H Vassilev, A Kurooka, H Ishiguro, K Sawada, J Ikura, T Korsmeyer, SJ Qin, J Herlitz, AM AF Nakatani, Y Konishi, H Vassilev, A Kurooka, H Ishiguro, K Sawada, J Ikura, T Korsmeyer, SJ Qin, J Herlitz, AM TI p600, a unique protein required for membrane morphogenesis and cell survival SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE apoptosis; cancer; calmodulin; retinoblastoma protein ID N-END RULE; RETINOBLASTOMA PROTEIN; APOPTOSIS; STABILIZATION; PURIFICATION; DYNAMICS; RECEPTOR; COMPLEX; BIOLOGY; CANCER AB in this article, we identify and characterize p600, a unique 600-kDa retinoblastoma protein- and calmodulin-binding protein. In the nucleus, p600 and retinoblastoma protein seem to act as a chromatin scaffold. In the cytoplasm, p600 and clathrin form a meshwork structure, which could contribute to cytoskeletal organization and membrane morphogenesis. Reduced expression of p600 with interference RNA abrogates integrin-mediated ruffled membrane formation and, furthermore, prevents activation of integrin-mediated survival pathways. Consequently, knockdown of p600 sensitizes cells to apoptosis induced by cell detachment. These findings provide mechanistic insight into the regulation of membrane-proximal events in tumorigenesis. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NICHHD, NIH, Bethesda, MD 20892 USA. Baylor Coll Med, Dept Biochem, Houston, TX 77030 USA. Baylor Coll Med, Dept Cell Biol, Houston, TX 77030 USA. RP Nakatani, Y (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. EM nakatani@mac.com NR 26 TC 32 Z9 35 U1 2 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 18 PY 2005 VL 102 IS 42 BP 15093 EP 15098 DI 10.1073/pnas.0507458102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 977NZ UT WOS:000232811800029 PM 16214886 ER PT J AU Bi, XL Srikanta, D Fanti, L Pimpinelli, S Badugu, R Kellum, R Rong, YKS AF Bi, XL Srikanta, D Fanti, L Pimpinelli, S Badugu, R Kellum, R Rong, YKS TI Drosophila ATM and ATR checkpoint kinases control partially redundant pathways for telomere maintenance SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE Mre11 and Nbs1; telomerase-independent mechanism; telomere capping; telomeric silencing ID ATAXIA-TELANGIECTASIA GENE; DNA-DAMAGE RESPONSE; HETEROCHROMATIN PROTEIN-1; SACCHAROMYCES-CEREVISIAE; CHROMOSOME BREAKAGE; MELANOGASTER; YEAST; COMPLEX; FUSION; REPAIR AB In higher eukaryotes, the ataxia telangiectasia mutated (ATM) and ATM and Rad3-related (ATR) checkpoint kinases play distinct, but partially overlapping, roles in DNA damage response. Yet their interrelated function has not been defined for telomere maintenance. We discover in Drosophila that the two proteins control partially redundant pathways for telomere protection: the loss of ATM leads to the fusion of some telomeres, whereas the loss of both ATM and ATR renders all telomeres susceptible to fusion. The ATM-controlled pathway includes the Mre11 and Nijmegen breakage syndrome complex but not the Chk2 kinase, whereas the ATR-regulated pathway includes its partner ATR-interacting protein but not the Chk1 kinase. This finding suggests that ATM and ATR regulate different molecular events at the telomeres compared with the sites of DNA damage. This compensatory relationship between ATM and ATR is remarkably similar to that observed in yeast despite the fact that the biochemistry of telomere elongation is completely different in the two model systems. We provide evidence suggesting that both the loading of telomere capping proteins and normal telomeric silencing requires ATM and ATR in Drosophila and propose that ATM and ATR protect telomere integrity by safeguarding chromatin architecture that favors the loading of telomere-elongating, capping, and silencing proteins. C1 NCI, Mol Cell Biol Lab, NIH, Bethesda, MD 20892 USA. Univ Roma La Sapienza, Dipartimento Genet & Biol Mol, I-00185 Rome, Italy. Univ Kentucky, Dept Biol, Lexington, KY 40506 USA. RP Rong, YKS (reprint author), NCI, Mol Cell Biol Lab, NIH, Bethesda, MD 20892 USA. EM rongy@mail.nih.gov RI Badugu, RamaKrishna/A-8572-2008; Bi, Xiaolin/E-7469-2010; Bi, Xiaolin/C-7038-2014 OI Bi, Xiaolin/0000-0002-7172-7851; Bi, Xiaolin/0000-0003-2837-9457 FU Intramural NIH HHS; NIGMS NIH HHS [R01 GM059765, GM059765] NR 49 TC 57 Z9 61 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 18 PY 2005 VL 102 IS 42 BP 15167 EP 15172 DI 10.1073/pnas.0504981102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 977NZ UT WOS:000232811800042 PM 16203987 ER PT J AU Wille-Reece, U Flynn, BJ Lore, K Koup, RA Kedl, RM Mattapallil, JJ Weiss, WR Roederer, M Seder, RA AF Wille-Reece, U Flynn, BJ Lore, K Koup, RA Kedl, RM Mattapallil, JJ Weiss, WR Roederer, M Seder, RA TI HIV Gag protein conjugated to a toll-like receptor 7/8 agonist improves the magnitude and quality of Th1 and CD8(+) T cell responses in nonhuman primates SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE vaccine; dendritic cell; cross-presentation; cellular immunity ID PLASMACYTOID DENDRITIC CELLS; CPG OLIGODEOXYNUCLEOTIDES; PROMOTE EXPANSION; INFLUENZA-VIRUS; RHESUS-MONKEYS; I INTERFERON; SUBSETS; ACTIVATION; IMMUNITY; ANTIGEN AB Induction and maintenance of antibody and T cell responses will be critical for developing a successful vaccine against HIV. A rational approach for generating such responses is to design vaccines or adjuvants that have the capacity to activate specific antigen-presenting cells. In this regard, dendritic cells (DCs) are the most potent antigen-presenting cells for generating primary T cell responses. Here, we report that Toll-like receptor (TLR) agonists and ligands that activate DCs in vitro influence the magnitude and quality of the cellular immune response in nonhuman primates (NHPs) when administered with HIV Gag protein. NHPs immunized with HIV Gag protein and a TLR7/8 agonist or a TLR9 ligand [CpG oligodeoxynucleotides (CpG ODN)] had significantly increased Gag-specific T helper I and antibody responses, compared with animals immunized with HIV Gag protein alone. importantly, conjugating the HIV Gag protein to the TLR7/8 agonist (Gag-TLR7/8 conjugate) dramatically enhanced the magnitude and altered the quality of the T helper 1 response, compared with animals immunized with HIV Gag protein and the TLR7/8 agonist or CpG ODN. Furthermore, immunization with the Gag-TLR7/8 conjugate vaccine elicited Gag-specific CD8(+) T responses. Collectively, our results show that conjugating HIV Gag protein to a TLR7/8 agonist is an effective way to elicit broad-based adaptive immunity in NHPs. This type of vaccine formulation should have utility in preventive or therapeutic vaccines in which humoral and cellular immunity is required. C1 NIH, Cellular Immunol Sect, Bethesda, MD 20892 USA. NIH, Immunol Lab, Bethesda, MD 20892 USA. NIH, ImmunoTechnol Sect, Vaccine Res Ctr, Bethesda, MD 20892 USA. 3M Pharmaceut, St Paul, MN 55144 USA. USN, Med Res Ctr, Malaria Program, Silver Spring, MD 20910 USA. RP Seder, RA (reprint author), NIH, Cellular Immunol Sect, Bldg 10, Bethesda, MD 20892 USA. EM rseder@mail.nih.gov RI Roederer, Mario/G-1887-2011 NR 31 TC 188 Z9 194 U1 2 U2 18 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 18 PY 2005 VL 102 IS 42 BP 15190 EP 15194 DI 10.1073/pnas.0507484102 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 977NZ UT WOS:000232811800046 PM 16219698 ER PT J AU Ali, IU Luke, BT Dean, M Greenwald, P AF Ali, IU Luke, BT Dean, M Greenwald, P TI Allellic variants in regulatory regions of cyclooxygenase-2: association with advanced colorectal adenoma SO BRITISH JOURNAL OF CANCER LA English DT Article DE cyclooxygenase-2; colorectal adenomas; polymorphisms; haplotypes ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; RANDOMIZED-TRIAL; GENE-EXPRESSION; PROMOTER VARIANT; POSTTRANSCRIPTIONAL CONTROL; HAPLOTYPE RECONSTRUCTION; CRE ELEMENTS; CANCER; ASPIRIN; RISK AB Cyclooxygenase 2 (Cox-2) is upregulated in colorectal adenomas and carcinomas. Polymorphisms in the Cox-2 gene may influence its function and/or its expression and may modify the protective effect of nonsteroidal anti-inflammatory drugs ( NSAIDs), thereby impacting individuals' risk of developing colorectal cancer and response to prevention/intervention strategies. In a nested case control study, four polymorphisms in the Cox-2 gene ( two in the promoter, - 663 insertion/deletion, GT/(GT) and - 798 A/G; one in intron 5-5229, T/G; one in 3' untranslated region (UTR)-8494, T/C) were genotyped in 726 cases of colorectal adenomas and 729 age- and gender-matched controls in the prostate, lung, colorectal, and ovarian (PLCO) cancer screening trial. There was no significant association between the Cox-2 polymorphisms and adenoma development in the overall population. However, in males, the relatively rare heterozygous genotype GT/( GT) at - 663 in the promoter and the variant homozygous genotype G/G at intron 55229 appeared to have inverse associations ( odds ratio ( OR) 0.59, confidence interval (CI): 0.34 - 1.02 and OR 0.48, CI: 0.24 - 0.99, respectively), whereas the heterozygous genotype T/C at 3'UTR-8494 had a positive association ( OR 1.31, CI: 1.01 - 1.71) with adenoma development. Furthermore, the haplotype carrying the risk-conferring 3'UTR-8494 variant was associated with a 35% increase in the odds for adenoma incidence in males ( OR 1.35, CI: 1.07 - 1.70), but the one with a risk allele at 3'UTR-8494 and a protective allele at intron 5-5229 had no effect on adenoma development ( OR 0.85, CI: 0.66 - 1.09). Gender-related differences in adenoma risk were also noted with tobacco usage and protective effects of NSAIDs. Our analysis underscores the significance of the overall allelic architecture of Cox-2 as an important determinant for risk assessment. C1 NCI, Div Canc Prevent, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, Frederick, MD 21702 USA. NCI, Adv Biomed Comp Ctr, SAIC, Frederick, MD 21702 USA. RP Ali, IU (reprint author), NCI, Div Canc Prevent, 6130 Execut Blvd, Bethesda, MD 20892 USA. EM alii@mail.nih.gov OI Dean, Michael/0000-0003-2234-0631 FU NCI NIH HHS [N01-CO-12400, N01CO12400, Z01 BC005652-15] NR 46 TC 33 Z9 36 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD OCT 17 PY 2005 VL 93 IS 8 BP 953 EP 959 DI 10.1038/sj.bjc.6602806 PG 7 WC Oncology SC Oncology GA 972ZL UT WOS:000232492400018 PM 16205694 ER PT J AU Saksena, R Ma, XQ Wade, TK Kovac, P Wade, WF AF Saksena, R Ma, XQ Wade, TK Kovac, P Wade, WF TI Effect of saccharide length on the immunogenicity of neoglycoconjugates from synthetic fragments of the O-SP of Vibrio cholerae O1, serotype Ogawa SO CARBOHYDRATE RESEARCH LA English DT Article DE Vibrio cholerae O1; cholera vaccine; Ogawa; LPS; conjugate; neoglycoconjugate ID MONOCLONAL-ANTIBODIES; PROTEIN CARRIER; LIPOPOLYSACCHARIDE; INABA; POLYSACCHARIDE; ANTIGEN; TOXIN; MICE; O-1; OLIGOSACCHARIDES AB A synthetic hexasaccharide, identical to the terminal hexasaccharide of Ogawa LPS, coupled to bovine serum albumin induced protective antibodies in mice. To determine if there was it minimum saccharide length required for immunogenicity and efficacy, shorter (mono- to pentasaccharide) neoglycoconjugates (CHO BSA) were tested in mice. The Ogawa CHO BSA was inoculated at either a constant mass but differing moles, or equal moles but differing masses. Humoral responses were essentially the same when mice received 9 mu g of the carbohydrate (0.007 mM with the pentasaccharide) in each of the neoglycoconjugates prepared from mono- through the pentasaccharide, or the same molar amount (0.007 mM), proportionally less by weight when going from the penta- to the monosaccharide. These data show that. within this dose range. the responses occurred virtually independently of the amount of immunogen. Humoral antibodies induced by these immunogens were generally not vibriocidal. Selected antisera induced by CHO-BSA immunogens were protective, but the ELISA titers of the sera were not predictive of the protective capacity. Purified, Ogawa LPS induced anti-Ogawa LPS IgM antibody titers similar to those induced by the Ogawa CHO BSA conjugates. The anti-whole LPS sera were strongly vibriocidal. as were the previously reported sera induced by hexasaccharide conjugates, This suggests either that the shorter oligosaccharides lack a conformational epitope provided by the hexasaccharide or that the LPS has additional B cell epitopes or selects different B cells in the primary response. (C) 2005 Elsevier Ltd. All rights reserved. C1 Dartmouth Coll Sch Med, Dept Microbiol & Immunol, Lebanon, NH 03756 USA. NIDDK, NIH, Med Chem Lab, Bethesda, MD 20892 USA. RP Wade, WF (reprint author), Dartmouth Coll Sch Med, Dept Microbiol & Immunol, 630W Borwell Bldg, Lebanon, NH 03756 USA. EM william.wade@dartmouth.edu FU Intramural NIH HHS; NIAID NIH HHS [AI 47373] NR 29 TC 20 Z9 21 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0008-6215 J9 CARBOHYD RES JI Carbohydr. Res. PD OCT 17 PY 2005 VL 340 IS 14 BP 2256 EP 2269 DI 10.1016/j.carres.2005.07.017 PG 14 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 967MQ UT WOS:000232095700005 PM 16098493 ER PT J AU Glass, WG Lim, JK Cholera, R Pletnev, AG Gao, JL Murphy, PM AF Glass, WG Lim, JK Cholera, R Pletnev, AG Gao, JL Murphy, PM TI Chemokine receptor CCR5 promotes leukocyte trafficking to the brain and survival in West Nile virus infection SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID CD8(+) T-CELLS; NEW-YORK; ENCEPHALITIS-VIRUS; IMMUNE-RESPONSES; UNITED-STATES; MICE; OUTBREAK; DEMYELINATION; INTERFERON; PROTECTION AB The molecular immunopathogenesis of West Nile virus (WNV) infection is poorly understood. Here, we characterize a mouse model for WNV using a subcutaneous route of infection and delineate leukocyte subsets and immunoregulatory factors present in the brains of infected mice. Central nervous system (CNS) expression of the chemokine receptor CCR5 and its ligand CCL5 was prominently up-regulated by WNV, and this was associated with CNS infiltration of CD4(+) and CD8(+) T cells, NK1.1(+) cells and macrophages expressing the receptor. The significance of CCR5 in pathogenesis was established by mortality studies in which infection of CCR5(-/-) mice was rapidly and uniformly fatal. In the brain, WNV-infected CCR5(-/-) mice had increased viral burden but markedly reduced NK1.1(+) cells, macrophages, and CD4(+) and CD8(+) T cells compared with WNV-infected CCR5(-/-) mice. Adoptive transfer of splenocytes from WNV-infected CCR5(-/-) mice into infected CCR5(-/-) mice increased leukocyte accumulation in the CNS compared with transfer of splenocytes from infected CCR5(-/-) mice into infected CCR5(-/-) mice, and increased survival to 60%, the same as in infected CCR5(-/-) control mice. We conclude that CCR5 is a critical antiviral and survival determinant in WNV infection of mice that acts by regulating trafficking of leukocytes to the infected brain. C1 NIAID, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Murphy, PM (reprint author), NIAID, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. EM pmm@nih.gov FU Intramural NIH HHS NR 40 TC 217 Z9 230 U1 1 U2 7 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD OCT 17 PY 2005 VL 202 IS 8 BP 1087 EP 1098 DI 10.1084/jem.20042530 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 979GD UT WOS:000232929500009 PM 16230476 ER PT J AU Palmeri, T Lowe, AM Sleeper, LA Saucedo, JF Desvigne-Nickens, P Hochman, AJS AF Palmeri, T Lowe, AM Sleeper, LA Saucedo, JF Desvigne-Nickens, P Hochman, AJS CA SHOCK Investigators TI Racial and ethnic differences in the treatment and outcome of cardiogenic shock following acute myocardial infarction SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID TRANSLUMINAL CORONARY ANGIOPLASTY; EARLY REVASCULARIZATION; ARTERY SURGERY; BLACK PATIENTS; CARE UNIT; RACE; SURVIVAL; MANAGEMENT; REGISTRY; SEX AB We investigated the association between race/ethnicity on the use of cardiac resources in patients who have acute myocardial infarction that is complicated by cardiogenic shock. The Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock (SHOCK) trial examined the effect of reperfusion and revascularization treatment strategies on mortality. Patients screened but not enrolled in the SHOCK Trial (n = 1,189) were entered into the SHOCK registry. Of the patients in the United States registry (n = 538) who had shock due to predominant left ventricular failure, 440 were characterized as white (82%), 42 as Hispanic (8%), 34 as African-American (6%), and 22 as Asian/other (4%). The use of invasive procedures differed significantly by race/ethnicity. Hispanic patients underwent coronary angiography significantly less often than did white patients (38 vs 66%, p = 0.002). Among those patients who underwent coronary angiography, there were no race/ethnicity differences in the proportion of patients who underwent revascularization (p = 0.353). Overall in-hospital mortality (57%) differed significantly by race/ethnicity (p = 0.05), with the highest mortality rate in Hispanic patients (74% vs 65% for African-Americans, 56% for whites, and 41% for Asian/other). After adjustment for patient characteristics and use of revascularization, there were no mortality differences by race/ethnicity (p = 0.262), with all race/ethnicity subgroups benefiting equally by revascularization. In conclusion, the SHOCK registry showed significant differences in the treatment and in-hospital mortality of Hispanic patients who had cardiogenic shock, with these patients being less likely to undergo percutaneous coronary intervention. Therefore, early revascularization should be strongly considered for all patients, independent of race/ethnicity, who develop cardiogenic shock after acute myocardial infarction. (c) 2005 Elsevier Inc. All rights reserved. C1 Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, New Brunswick, NJ USA. New England Res Inst, Watertown, MA 02172 USA. Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. NHLBI, Bethesda, MD 20892 USA. NYU, Sch Med, New York, NY USA. RP Palmeri, T (reprint author), Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, New Brunswick, NJ USA. EM palmerse@umdnj.edu OI Hochman, Judith/0000-0002-5889-5981 FU NHLBI NIH HHS [R01-HL50020] NR 29 TC 3 Z9 4 U1 0 U2 2 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD OCT 15 PY 2005 VL 96 IS 8 BP 1042 EP 1049 DI 10.1016/j.amjcard.2005.06.033 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 977MZ UT WOS:000232809200002 PM 16214435 ER PT J AU Wang, XL Thayer, JF Treiber, F Snieder, H AF Wang, XL Thayer, JF Treiber, F Snieder, H TI Ethnic differences and heritability of heart rate variability in African- and European American youth SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID RESPIRATORY SINUS ARRHYTHMIA; GEORGIA CARDIOVASCULAR TWIN; BLOOD-PRESSURE RESPONSE; NORMOTENSIVE BLACKS; AGE; GENDER; CAPACITY; EVENTS; TASK; RACE AB This study investigated whether heart rate variability (HRV) in young African-Americans differed from that in young European Americans. It further examined the genetic and/or environmental sources of HRV variance and to what extent they depend on ethnicity or gender in young twins. Subjects were available from 1 data set including 166 subjects (mean age 16 +/- 2 years; 63 African-Americans) and another including 219 twins (11 singletons [4 African-Americans] and 104 pairs [42 African-Americans]; mean age 15 2 years). HRV was measured over 256 RR intervals in a supine position. Two time-domain variables, the SD of normal RR intervals (SDNN) and the root-mean-square of successive differences (RMSSD) of normal RR,intervals, and 3 frequency-domain variables, high-frequency (HF) power, low-frequency (LF) power, and the LF power/HF power ratio, were used. African-Americans had higher RMSSDs (p <0.01) and HF power (p = 0.047) and lower LF power HF power ratios (p <0.01) than European Americans. These differences remained significant after adjusting for covariates. All HRV parameters were heritable; estimated heritability ranged from 32% to 71%. Model fitting showed no ethnic or gender differences for any measure. SDNN, RMSSD, and HF power were strongly correlated (r values >0.8). One factor explaining, >90% of the variance for all 3 measures was identified. The heritability of this combined HRV-score was 70%. In conclusion, this study suggests that ethnic differences in HRV already exist in youth, with African-Americans having greater HRV than European Americans. High heritability estimates for HRV measures were observed, and no differences in HRV heritability estimates were noted for ethnicity or gender. (c) 2005 Elsevier Inc. All rights reserved. C1 Med Coll Georgia, Georgia Prevent Inst, Dept Pediat, Augusta, GA 30912 USA. NIA, Emot & Quantitat Psychophysiol Sect, Ctr Gerontol Res, Baltimore, MD 21224 USA. St Thomas Hosp, Twin Res & Genet Epidemiol Unit, London, England. RP Snieder, H (reprint author), Med Coll Georgia, Georgia Prevent Inst, Dept Pediat, Augusta, GA 30912 USA. EM hsnieder@mcg.edu NR 30 TC 5 Z9 5 U1 0 U2 4 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD OCT 15 PY 2005 VL 96 IS 8 BP 1168 EP 1174 DI 10.1016/j.amjcard.2005.06.050 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 977MZ UT WOS:000232809200025 ER PT J AU Longnecker, MP AF Longnecker, MP TI Invited commentary: Why DDT matters now SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Editorial Material ID MALARIA CONTROL; BREAST-CANCER; EXPOSURE; SERUM C1 NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Longnecker, MP (reprint author), NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, POB 12233,MD A3-05, Res Triangle Pk, NC 27709 USA. EM longnec1@niehs.nih.gov OI Longnecker, Matthew/0000-0001-6073-5322 NR 26 TC 36 Z9 38 U1 0 U2 6 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 15 PY 2005 VL 162 IS 8 BP 726 EP 728 DI 10.1093/aje/kwi277 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 971ZG UT WOS:000232423000003 PM 16120697 ER PT J AU Rose, PS Levy, HP Liberfarb, RM Davis, J Szymko-Bennett, Y Rubin, BI Tsilou, E Griffith, AJ Francomano, CA AF Rose, PS Levy, HP Liberfarb, RM Davis, J Szymko-Bennett, Y Rubin, BI Tsilou, E Griffith, AJ Francomano, CA TI Stickler syndrome: Clinical characteristics and diagnostic criteria SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE Stickler syndrome; diagnostic criteria; nosology ID PROGRESSIVE ARTHRO-OPHTHALMOPATHY; MITRAL-VALVE-PROLAPSE; COL11A1 GENE; II COLLAGEN; SYNDROME ARTHROOPHTHALMOPATHY; VITREOUS PHENOTYPE; NATURAL-HISTORY; SYNDROME TYPE-2; XI COLLAGEN; FOLLOW-UP AB The purpose of this study was to establish diagnostic criteria for Stickler syndrome. Ninety patients from 38 families had complete evaluations for possible Stickler syndrome. Molecular confirmation of COL2A1 mutation status (type I Stickler syndrome) was available on 25 patients from six families. In the remaining 65 patients, 47 from 25 families were affected with Stickler syndrome and 18 from seven families were unaffected with Stickler syndrome. A diagnostic nosology based on type I Stickler patients with known COL2A1 mutations was applied to clinically affected and unaffected patients. A diagnostic scale of 9 points evaluated molecular data or family history data and characteristic ocular, orofacial, auditory, and musculoskeletal findings. A score of >= 5 was diagnostic of Stickler syndrome. These criteria demonstrate 100% sensitivity when applied to type I Stickler syndrome patients with known COL2A1 mutations, 98% sensitivity when applied to clinically affected Stickler patients, and 86% specificity when applied to patients unaffected based on clinical and/or molecular analysis. We conclude that diagnostic criteria based on type I Stickler patients with molecularly confirmed COL2A1 mutations appear to be sensitive and specific for the diagnosis of this syndrome and should be helpful to clinicians when making the diagnosis. (c) 2005 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Genet & Teratol Unit, Boston, MA 02114 USA. Mayo Clin, Dept Orthoped Surg, Rochester, MN USA. Johns Hopkins Univ, Baltimore, MD USA. NIA, Genet Lab, NIH, Baltimore, MD 21224 USA. NHGRI, NIH, Bethesda, MD 20892 USA. Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD USA. NEI, NIH, Bethesda, MD 20892 USA. RP Liberfarb, RM (reprint author), Massachusetts Gen Hosp, Genet & Teratol Unit, Warren 801, Boston, MA 02114 USA. EM rml@massmed.org FU Intramural NIH HHS NR 62 TC 36 Z9 41 U1 0 U2 6 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 15 PY 2005 VL 138A IS 3 BP 199 EP 207 DI 10.1002/ajmg.a.30955 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 969MW UT WOS:000232239300002 PM 16152640 ER PT J AU Wilkes, DS Egan, TM Reynolds, HY AF Wilkes, DS Egan, TM Reynolds, HY TI Lung transplantation - Opportunities for research and clinical advancement SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Review DE allograft dysfunction; infection; ischemia-reperfusion injury; lung transplantation; obliterative bronchiolitis; rejection ID BRONCHIOLITIS-OBLITERANS-SYNDROME; ISCHEMIA-REPERFUSION INJURY; HEART-BEATING DONORS; SURFACTANT PROTEIN-A; BRONCHOALVEOLAR LAVAGE FLUID; ACUTE ALLOGRAFT-REJECTION; GROWTH-FACTOR-BETA; GASTROESOPHAGEAL-REFLUX DISEASE; RAT ALVEOLAR MACROPHAGES; NITRIC-OXIDE SYNTHASE AB Lung transplantation is the only definitive therapy for many forms of end-stage lung diseases. However, the success of lung transplantation is limited by many factors: (1) Too few lungs available for transplantation due to limited donors or injury to the donor lung; (2) current methods of preservation of excised lungs do not allow extended periods of time between procurement and implantation; (3) acute graft failure is more common with lungs than other solid organs, thus contributing to poorer short-term survival after lung transplant compared with that for recipients of other organs; (4) lung transplant recipients are particularly vulnerable to pulmonary infections; and (5) chronic allograft dysfunction, manifest by bronchiolitis obliterans syndrome, is frequent and limits long-term survival. Scientific advances may provide significant improvements in the outcome of lung transplantation. The National Heart, Lung, and Blood Institute convened a working group of investigators on June 14-15, 2004, in Bethesda, Maryland, to identify opportunities for scientific advancement in lung transplantation, including basic and clinical research. This workshop provides a framework to identify critical issues related to clinical lung transplantation, and to delineate important areas for productive scientific investigation. C1 NHLBI, DLD, Bethesda, MD 20892 USA. Univ N Carolina, Chapel Hill, NC 27514 USA. Indiana Univ, Sch Med, Indianapolis, IN USA. RP Reynolds, HY (reprint author), NHLBI, DLD, 2 Rockledge Ctr,6701 Rockledge Dr, Bethesda, MD 20892 USA. EM reynoldh@mail.nih.gov RI Gough, Ethan/B-8633-2012 NR 161 TC 65 Z9 68 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD OCT 15 PY 2005 VL 172 IS 8 BP 944 EP 955 DI 10.1164/rccm.200501-098WS PG 12 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 975OM UT WOS:000232671800004 PM 16020804 ER PT J AU Bullard, JE Wert, SE Whitsett, JA Dean, M Nogee, LM AF Bullard, JE Wert, SE Whitsett, JA Dean, M Nogee, LM TI ABCA3 mutations associated with pediatric interstitial lung disease SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE desquamative interstitial pneumonitis; pulmonary alveolar proteinosis; surfactant ID FATAL SURFACTANT DEFICIENCY; LAMELLAR BODY MEMBRANE; PROTEIN-C; PULMONARY SURFACTANT; II CELLS; SP-B; PNEUMONITIS; POPULATION; FIBROSIS; NEWBORNS AB Rationale: ABCA3 is a member of the ATP-binding cassette family of proteins that mediate the translocation of a wide variety of substrates, including lipids, across cellular membranes. Mutations in the gene encoding ABCA3 were recently identified in full-term neonates with fatal surfactant deficiency. Objective: To test the hypothesis that ABCA3 mutations are not always associated with fatal neonatal lung disease but are a cause of pediatric interstitial lung disease. Methods: DNA samples were obtained from 195 children with chronic lung disease of unknown etiology. The 30 coding exons of the ABCA3 gene were sequenced in four unrelated children with a referring diagnosis of desquamative interstitial pneumonitis and who were older than 10 years at the time of enrollment. Results: Three of four patients (ages 16, 23, and 11 years) with desquamative interstitial pneumonitis had ABCA3 mutations identified on both alleles. All three had the same missense mutation (E292v) and a second unique mutation. The E292V mutation was not found on 200 control alleles from adults without lung disease, but seven additional patients of the remaining study patients had the E292V mutation on one allele. Immunohistochemical analysis of surfactant protein expression in three patients revealed a specific staining pattern for surfactant protein-B, which was the same pattern observed in several infants with fatal lung disease due to ABCA3 mutations. Conclusion: ABCA3 mutations cause some types of interstitial lung disease in pediatric patients. C1 Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Univ Cincinnati, Coll Med, Dept Pediat, Cincinnati, OH USA. Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA. NCI, Lab Genom Divers, Human Genet Sect, Frederick, MD 21701 USA. RP Nogee, LM (reprint author), Div Neonatol, CMSC 6-104,600 N Wolfe St, Baltimore, MD 21287 USA. EM lnogee@jhmi.edu RI Dean, Michael/G-8172-2012 OI Dean, Michael/0000-0003-2234-0631 FU NHLBI NIH HHS [P50 HL056387, HL-54703, HL-56387, R01 HL054703] NR 26 TC 153 Z9 162 U1 0 U2 4 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD OCT 15 PY 2005 VL 172 IS 8 BP 1026 EP 1031 DI 10.1164/rccm.200503-504OC PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 975OM UT WOS:000232671800015 PM 15976379 ER PT J AU Hasler, G Gergen, PJ AF Hasler, G Gergen, PJ TI Where are the guidelines for the treatment of asthma with panic spectrum symptoms? Reply SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Letter C1 NIMH, NIH, Bethesda, MD 20892 USA. Psychiat Univ Hosp, Zurich, Switzerland. NIAID, NIH, Bethesda, MD 20892 USA. RP Hasler, G (reprint author), NIMH, NIH, Bethesda, MD 20892 USA. RI Hasler, Gregor/E-4845-2012 OI Hasler, Gregor/0000-0002-8311-0138 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD OCT 15 PY 2005 VL 172 IS 8 BP 1056 EP 1056 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 975OM UT WOS:000232671800023 ER PT J AU Hall, D Minton, AP AF Hall, D Minton, AP TI Turbidity as a probe of tubulin polymerization kinetics: A theoretical and experimental re-examination SO ANALYTICAL BIOCHEMISTRY LA English DT Article DE tubulin; microtubules; kinetics; polymerization; characterization ID MICROTUBULE ASSEMBLY INVITRO; PROTEIN; TAXOL; MODEL; MACROMOLECULES; MECHANISM AB We report here an examination of the validity of the experimental practice of using solution turbidity to study the polymerization kinetics of microtubule formation. The investigative approach proceeds via numerical solution of model rate equations to yield the time dependence of each microtubule species, followed by the calculation of the time- and wavelength-dependent turbidity generated by the calculated distribution of rod lengths. The wavelength dependence of the turbidity along the time course is analyzed to search for generalized kinetic regimes that satisfy a constant proportionality relationship between the observed turbidity and the weight concentration of polymerized tubulin. An empirical analysis, which permits valid interpretation of turbidity data for distributions of microtubules that are not long relative to the wavelength of incident light, is proposed. The basic correctness of the simulation work is shown by the analysis of the experimental time dependence of the turbidity wavelength exponent for microtubule formation in taxol-supplemented 0.1 M Pipes buffer (1 mM GTP, 1 mM EGTA, 1 mM MgSO4, pH 6.4). We believe that the general findings and principles outlined here are applicable to studies of other fibril-forming systems that use turbidity as a marker of polymerization progress. Crown Copyright (C) 2005 Published by Elsevier Inc. All rights reserved. C1 Univ Cambridge, Dept Chem, Cambridge CB2 1EW, England. NIDDKD, Sect Phys Biochem, NIH, Bethesda, MD 20892 USA. RP Hall, D (reprint author), Univ Cambridge, Dept Chem, Lensfield Rd, Cambridge CB2 1EW, England. EM drh32@cam.ac.uk RI Hall, Damien/D-9927-2012; OI Hall, Damien/0000-0003-1538-7618; Minton, Allen/0000-0001-8459-1247 NR 29 TC 25 Z9 25 U1 1 U2 8 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD OCT 15 PY 2005 VL 345 IS 2 BP 198 EP 213 DI 10.1016/j.ab.2005.07.011 PG 16 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 972CP UT WOS:000232431900004 PM 16129407 ER PT J AU Wang, YJ Rudnick, PA Evans, EL Li, J Zhuang, ZP DeVoe, DL Lee, CS Balgley, BM AF Wang, YJ Rudnick, PA Evans, EL Li, J Zhuang, ZP DeVoe, DL Lee, CS Balgley, BM TI Proteome analysis of microdissected tumor tissue using a capillary isoelectric focusing-based multidimensional separation platform coupled with ESI-tandem MS SO ANALYTICAL CHEMISTRY LA English DT Article ID LASER-CAPTURE MICRODISSECTION; COLLISION-INDUCED DISSOCIATION; PARAFFIN-EMBEDDED TISSUES; MASS-SPECTROMETRY; IDENTIFICATION TECHNOLOGY; SHOTGUN PROTEOMICS; SHEWANELLA-ONEIDENSIS; GEL ELECTROPHORESIS; CLINICAL PROTEOMICS; EXPRESSION PROFILES AB This study demonstrates the ability to perform sensitive proteome analysis on the limited protein quantities available through tissue microdissection. Capillary isoelectric focusing combined with nano-reversed-phase liquid chromatography in an automated and integrated platform not only provides systematic resolution of complex peptide mixtures based on their differences in isoelectric point and hydrophobicity but also eliminates peptide loss and analyte dilution. In comparison with strong cation exchange chromatography, the significant advantages of electrokinetic focusing-based separations include high resolving power, high concentration and narrow analyte bands, and effective usage of electrospray ionization-tandem MS toward peptide identifications. Through the use of capillary isoelectric focusing-based multidimensional peptide separations, a total of 6866 fully tryptic peptides were detected, leading to the identification of 1820 distinct proteins. Each distinct protein was identified by at least one distinct peptide sequence. These high mass accuracy and high-confidence identifications were generated from three proteome runs of a single glioblastoma multiforme tissue sample, each run consuming only 10 mu g of total protein, an amount corresponding to 20 000 selectively isolated cells. Instead of performing multiple runs of multidimensional separations, the overall peak capacity can be greatly enhanced for mining deeper into tissue proteomics by increasing the number of CIEF fractions without an accompanying increase in sample consumption. C1 Calibrant Biosyst, Gaithersburg, MD 20878 USA. Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA. Univ Maryland, Dept Mech Engn, College Pk, MD 20742 USA. Univ Maryland, Bioengn Program, College Pk, MD 20742 USA. NINDS, Mol Pathogenesis Unit, Surg Neurol Branch, Bethesda, MD 20892 USA. RP Balgley, BM (reprint author), Calibrant Biosyst, 910 Clopper Rd,Suite 220N, Gaithersburg, MD 20878 USA. EM brian.balgley@calibrant.com RI DeVoe, Don/A-2891-2011; OI DeVoe, Don/0000-0002-7740-9993; Balgley, Brian/0000-0002-3509-4567 FU NCI NIH HHS [CA103086, CA107988]; NCRR NIH HHS [RR21239] NR 50 TC 70 Z9 71 U1 0 U2 7 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 15 PY 2005 VL 77 IS 20 BP 6549 EP 6556 DI 10.1021/ac050491b PG 8 WC Chemistry, Analytical SC Chemistry GA 977ET UT WOS:000232785900005 PM 16223239 ER PT J AU Xu, X Veenstra, TD Fox, SD Roman, JM Issaq, HJ Falk, R Saavedra, JE Keefer, LK Ziegler, RG AF Xu, X Veenstra, TD Fox, SD Roman, JM Issaq, HJ Falk, R Saavedra, JE Keefer, LK Ziegler, RG TI Measuring fifteen endogenous estrogens simultaneously in human urine by high-performance liquid chromatography-mass spectrometry SO ANALYTICAL CHEMISTRY LA English DT Article ID 16 ALPHA-HYDROXYESTRONE; BREAST-CANCER RISK; CATECHOL ESTROGENS; RADIOIMMUNOASSAY; 2-HYDROXYESTRONE; STEROIDS; ASSAY; METABOLITES; MECHANISMS; PLASMA AB A sensitive, specific, accurate, and precise high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry method for measuring the, absolute quantities of 15 endogenous estrogens and their. metabolites in human urine has been developed and validated. The method requires a single hydrolysis/ extraction/derivatization step and only 0.5 mL of urine, yet is capable of simultaneously quantifying estrone and its 2-, 4-methoxy and 2-, 4-, and 16 alpha-hydroxy derivatives, and 2-hydroxyestrone-3-methyl ether; estradiol and its 2-, 4-methoxy and 2-, 16 alpha-hydroxy derivatives, 16-epiestriol, 17-epiestriol, and 16-ketoestradiol in pre- and postmenopausal women as well as men. Standard curves are linear over a 10(3)-fold concentration range with the standard error of the estimate (SEE) and the relative standard error of the estimate (RSEE) for the linear regression line ranging from 0.0131 to 0.1760 and 1.2 to 7.3%, respectively. The lower limit of quantitation for each estrogen is 0.02 ng/0.5 mL urine sample (2 pg on column), with the percent recovery of a known added amount of compound (accuracy) of 96-107% and an overall precision, including the hydrolysis, extraction, and derivatization steps, of 1-5% relative standard deviation (RSD) for samples prepared concurrently and 1-12% RSD for samples prepared in separate batches. Since individual patterns of estrogen metabolism may influence the risk of breast cancer, accurate, precise, and specific measurement of endogenous estrogen metabolites in biological matrixes will facilitate future research on breast cancer prevention, screening, and treatment. C1 NCI, Lab Proteom & Analyt Technol, SAIC Frederick Inc, Frederick, MD 21702 USA. NCI, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, Frederick, MD 21702 USA. NCI, Comparat Carcinogenesis Lab, Canc Res Ctr, Frederick, MD 21702 USA. NCI, Basic Res Program, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Veenstra, TD (reprint author), NCI, Lab Proteom & Analyt Technol, SAIC Frederick Inc, Frederick, MD 21702 USA. EM veenstra@ncifcrf.gov RI Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 FU NCI NIH HHS [N01-CO-12400] NR 28 TC 143 Z9 144 U1 4 U2 25 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 15 PY 2005 VL 77 IS 20 BP 6646 EP 6654 DI 10.1021/ac050697c PG 9 WC Chemistry, Analytical SC Chemistry GA 977ET UT WOS:000232785900018 PM 16223252 ER PT J AU Wang, HYJ Jackson, SN McEuen, J Woods, AS AF Wang, HYJ Jackson, SN McEuen, J Woods, AS TI Localization and analyses of small drug molecules in rat brain tissue sections SO ANALYTICAL CHEMISTRY LA English DT Article ID ASSISTED-LASER-DESORPTION/IONIZATION; TOF MASS-SPECTROMETRY; PROTEINS; COCAINE; MS; PHOSPHOLIPIDS; PEPTIDES; TOOL AB Traditional detection of drugs in tissue requires tissue homogenization, which precludes the mapping and localization of drugs. The use of autoradiography could compensate for such shortcoming. However, it requires expensive custom-synthesized radioactive drugs. Recent improvement in sample preparation for matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) and MALDI-MS/MS provides an alternative approach for in situ drug detection. In this work, rat brains were collected after intracranial injection of chlorisondamine or intraperitoneal injection of cocaine and snap frozen. MALDI matrixes were applied directly to 14-mu m brain cryosections and spectra acquired. The identity of the drugs was further confirmed by MS/MS. Careful matrix selection and tissue preparation allows for the successful detection of drugs and the mapping of their relative abundance across various regions of the brain. This new method is simple, safe, accurate, fast, cost-effective, and low in sample consumption and shows potential for imaging, pharmacokinetics, and toxicology applications. C1 NIDA, Cellular Neurobiol Branch, IRP, NIH, Baltimore, MD 21224 USA. RP Woods, AS (reprint author), NIDA, Cellular Neurobiol Branch, IRP, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM awoods@intra.nida.nih.gov NR 23 TC 62 Z9 64 U1 0 U2 9 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 15 PY 2005 VL 77 IS 20 BP 6682 EP 6686 DI 10.1021/ac050868d PG 5 WC Chemistry, Analytical SC Chemistry GA 977ET UT WOS:000232785900022 PM 16223256 ER PT J AU Ward, MM Weisman, MH Davis, JC Reveille, JD AF Ward, MM Weisman, MH Davis, JC Reveille, JD TI Risk factors for functional limitations in patients with long-standing ankylosing spondylitis SO ARTHRITIS & RHEUMATISM-ARTHRITIS CARE & RESEARCH LA English DT Article DE ankylosing spondylitis; disability; functional limitations; work ID QUALITY-OF-LIFE; RHEUMATOID-ARTHRITIS; WORK DISABILITY; HEALTH; INDEX; PREDICTORS; ABILITY; DISEASE AB Objective. To identify risk factors for functional limitations in patients with ankylosing spondylitis (AS) of at least 20 years' duration. Methods. Patients with AS for >= 20 years were enrolled in the cross-sectional component of the Prospective Study of Outcomes in AS. All patients had clinical evaluations and completed questionnaires on functional limitations and potential risk factors. Functional limitations were assessed using the Bath Ankylosing Spondylitis. Functional Index (BASFI; score range 0-100, higher scores indicate more limitations) and the Health Assessment Questionnaire for the Spondylarthropathies (HAQS). Risk factors included demographic characteristics, duration of AS, smoking status, number of comorbid medical conditions, recalled level of recreational activity in teens and twenties, occupational physical activity throughout life (rated 1 = little, 2 = moderate, 3 = heavy, and weighted by the number of years in each job), and history of AS in a first-degree relative. Results. The 326 patients (74% men) had a mean +/- SD age of 55.0 +/- 10.7 years, a mean duration of AS symptoms of 31.7 +/- 10.2 years, and a mean BASFI score of 40.7 +/- 25.6. BASFI scores increased with higher lifetime occupational physical activity (r = 0.31; P < 0.0001), the number of comorbid conditions (r = 0.25; P < 0.0001), and the duration of AS (r = 0.12; P = 0.04). BASFI scores were higher among current smokers compared with former/nonsmokers (55.5 versus 38.9; P = 0.0002), and among nonwhites compared with whites (49.9 versus 39.3; P = 0.02). In multivariable analyses, lifetime occupational physical activity, current smoking, education level, number of comorbid conditions, and family history were significantly associated with BASFI scores. The same risk factors were associated with the HAAS. Conclusion. Functional limitations in patients with AS for >= 20 years are greater among those with a history of more physically demanding jobs, more comorbid conditions, and among smokers, and are less severe among those with higher levels of education and a family history of AS. C1 NIAMS, US Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Texas, Hlth Sci Ctr, Houston, TX USA. RP Ward, MM (reprint author), NIAMS, IRP, NIH, Bldg 10 CRC,Room 4-1339,10 Ctr Dr,MSC 1468, Bethesda, MD 20892 USA. EM wardm1@mail.nih.gov FU Intramural NIH HHS [Z99 AR999999]; NCRR NIH HHS [M01 RR000079, M01 RR000425, M01 RR002558, M01-RR00079, M01-RR00425, M01-RR02558]; NIAMS NIH HHS [AR-46208, AR-48465, R01 AR046208, R01 AR048465] NR 36 TC 62 Z9 65 U1 0 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRIT RHEUM-ARTHR JI Arthritis Rheum-Arthritis Care Res. PD OCT 15 PY 2005 VL 53 IS 5 BP 710 EP 717 DI 10.1002/art.21445 PG 8 WC Rheumatology SC Rheumatology GA 982DE UT WOS:000233137300014 PM 16208654 ER PT J AU Costin, GE Valencia, JC Wakamatsu, K Ito, S Solano, F Milac, AL Vieira, WD Yamaguchi, Y Rouzaud, F Petrescu, AJ Lamoreux, ML Hearing, VJ AF Costin, GE Valencia, JC Wakamatsu, K Ito, S Solano, F Milac, AL Vieira, WD Yamaguchi, Y Rouzaud, F Petrescu, AJ Lamoreux, ML Hearing, VJ TI Mutations in dopachrome tautomerase (Dct) affect eumelanin/pheomelanin synthesis, but do not affect intracellular trafficking of the mutant protein SO BIOCHEMICAL JOURNAL LA English DT Article DE dopachrome tautomerase (Dct); eumelanin; melanocyte; pheomelanin; pigmentation; slaty AB Dopachrome tautomerase (Dct) is a type I membrane protein and an important regulatory enzyme that plays a pivotal role in the biosynthesis of melanin and in the rapid metabolism of its toxic intermediates. Dct-mutant melanocytes carrying the slaty or slaty light mutations were derived from the skin of newborn congenic C57BL/6J non-agouti black mice and were used to study the effect(s) of these mutations on the intracellular trafficking of Dct and on the pigmentation of the cells. Dct activity is 3-fold lower in slaty cells compared with non-agouti black melanocytes, whereas slaty light melanocytes have a surprisingly 28-fold lower Dct activity. Homology modelling of the active site of Dct suggests that the slaty mutation [R194Q (Arg(194) -> Gln)] is located in the active site and may alter the ability of the enzyme to transform the substrate. Transmembrane prediction methods indicate that the slaty light mutation [G486R (Gly(486) -> Arg)] may result in the sliding of the transmembrane domain towards the N-terminus, thus interfering with Dct function. Chemical analysis showed that both Dct mutations increase pheomelanin and reduce eumelanin produced by melanocytes in culture. Thus the enzymatic activity of Dct may play a role in determining whether the eumelanin or pheomelanin pathway is preferred for pigment biosynthesis. C1 NCI, Cell Biol Lab, Pigment Cell Biol Sect, NIH, Bethesda, MD 20892 USA. Fujita Hlth Univ, Sch Hlth Sci, Toyoake, Aichi, Japan. Univ Murcia, Sch Med, Dept Biochem & Mol Biol, Murcia, Spain. Romanian Acad, Inst Biochem, Bucharest, Romania. Texas A&M Univ, Dept Vet Pathobiol, College Stn, TX USA. RP Hearing, VJ (reprint author), NCI, Cell Biol Lab, Pigment Cell Biol Sect, NIH, Bethesda, MD 20892 USA. EM hearingv@nih.gov RI Yamaguchi, Yuji/B-9312-2008; Milac, Adina/C-1070-2011; Petrescu, Andrei-Jose/G-4576-2016; Solano, Francisco/G-5001-2013; OI Milac, Adina/0000-0003-1845-4281; Petrescu, Andrei-Jose/0000-0002-4478-3946; Solano, Francisco/0000-0001-9612-761X; Ito, Shosuke/0000-0001-9182-5144; Wakamatsu, Kazumasa/0000-0003-1748-9001 FU Wellcome Trust NR 50 TC 35 Z9 37 U1 0 U2 6 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD OCT 15 PY 2005 VL 391 BP 249 EP 259 DI 10.1042/BJ20042070 PN 2 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 980DF UT WOS:000232993400011 PM 15960609 ER PT J AU Ernst, M Paulus, MP AF Ernst, M Paulus, MP TI Neurobiology of decision making: A selective review from a neurocognitive and clinical perspective SO BIOLOGICAL PSYCHIATRY LA English DT Review DE anticipation; anxiety; choice selection; development; motivation; schizophrenia ID ANTERIOR CINGULATE CORTEX; METHAMPHETAMINE-DEPENDENT SUBJECTS; VENTRAL PREFRONTAL CORTEX; SOMATIC MARKER HYPOTHESIS; FRONTAL-LOBE DAMAGE; HUMAN BRAIN; ORBITOFRONTAL CORTEX; FUTURE CONSEQUENCES; NUCLEUS-ACCUMBENS; UTILIZATION BEHAVIOR AB we present a temporal map of key processes that occur during decision making, which consists of three stages: 1) formation of preferences among options, 2) selection and execution of an action, and 3) experience or evaluation of an outcome. This framework can be used to integrate findings of traditional choice psycbology neuropsychology, brain lesion studies, and functional neuroimaging. Decision making is distributed across various brain centers, which are differentially active across these stages of decision making. This approach can be used to follow developmental trajectories of the different stages of decision making and to identify unique deficits associated with distinct psychiatric disorders. C1 NIMH, Sect Dev & Affect Neurosci, Mood & Anxiety Disorders Program, NIH,HHS, Bethesda, MD 20892 USA. Univ Calif San Diego, Lab Biol Dynam & Theoret Med, San Diego, CA 92103 USA. Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. Vet Affairs San Diego Healthcare Syst, San Diego, CA USA. RP Ernst, M (reprint author), NIMH, Sect Dev & Affect Neurosci, Mood & Anxiety Disorders Program, NIH,HHS, 15K North Dr, Bethesda, MD 20892 USA. EM ernstm@mail.nih.gov NR 138 TC 222 Z9 229 U1 10 U2 28 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 EI 1873-2402 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD OCT 15 PY 2005 VL 58 IS 8 BP 597 EP 604 DI 10.1016/j.biopsych.2005.06.004 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 981NU UT WOS:000233096100001 PM 16095567 ER PT J AU Jazbec, S McClure, E Hardin, M Pine, DS Ernst, M AF Jazbec, S McClure, E Hardin, M Pine, DS Ernst, M TI Cognitive control under contingencies in anxious and depressed adolescents: An antisaccade task SO BIOLOGICAL PSYCHIATRY LA English DT Article DE anticipation; eye movement; latency; motivation; peak velocity; punishment; reward ID ANTERIOR CINGULATE CORTEX; SACCADIC EYE-MOVEMENTS; RESPONSE-INHIBITION; CHILDHOOD ANXIETY; PREFRONTAL CORTEX; MOOD DISORDERS; PERFORMANCE; ATTENTION; CHILDREN; INFORMATION AB Background: Emotion-related perurbations in cognitive control characterize adult mood and anxiety disorders. Fewer data are available to confirm such deficits in youth. Studies of cognitive control and error processing can provide an ideal template to examine these perturbations. Antisaccade paradigms are particularly well suited for this endeavor because they provide exquisite behavioral measures of modulation of response errors. Methods: A new monetary reward antisaccade task was used with 28 healthy, 11 anxious, and 12 depressed adolescent. Performance accuracy, saccade latency, and peak. velocity of incorrect responses were analyzed. Results: Performance accuracy across all groups was improved by incentives (obtain reward, avoid punishment). However, modulation of saccade errors by incentives differed by groups. In incentive trials relative to neutral trials, inhibitory efficiency (saccade latency) was enhanced in healthy, unaffected in depressed, and diminished in anxious adolescents. Modulation of errant actions (saccade peak velocity) was improved in the healthy group and unchanged in both the anxious and depressed groups. Conclusions: These findings provide grounds for testing hypotheses related to the impact of motivation deficits and emotional interference on directed action in adolescents with mood and anxiety disorders. Furthermore. neural mechanisms can now be examined by using ibis task paired with functional neuroimaging. C1 NIMH, Sect Dev & Affect Neurosci, Mood & Anxiety Disorders Program, NIH,HHS, Bethesda, MD 20892 USA. RP Ernst, M (reprint author), NIMH, Sect Dev & Affect Neurosci, Mood & Anxiety Disorders Program, NIH,HHS, 15K North Dr, Bethesda, MD 20892 USA. EM ernstm@mail.nih.gov NR 41 TC 62 Z9 63 U1 1 U2 19 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 15 PY 2005 VL 58 IS 8 BP 632 EP 639 DI 10.1016/j.biopsych.2005.04.010 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 981NU UT WOS:000233096100005 PM 16018983 ER PT J AU Pavletic, SZ AF Pavletic, SZ TI Transplantation for SLE? SO BLOOD LA English DT Editorial Material ID STEM-CELL TRANSPLANTATION; SYSTEMIC-LUPUS-ERYTHEMATOSUS C1 NCI, Bethesda, MD 20892 USA. RP Pavletic, SZ (reprint author), NCI, Bethesda, MD 20892 USA. NR 5 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD OCT 15 PY 2005 VL 106 IS 8 BP 2597 EP 2597 DI 10.1182/blood-2005-08-3092 PG 1 WC Hematology SC Hematology GA 972PP UT WOS:000232466000003 ER PT J AU Gao, P Wange, RL Zhang, N Oppenheim, JJ Howard, OMZ AF Gao, P Wange, RL Zhang, N Oppenheim, JJ Howard, OMZ TI Negative regulation of CXCR4-mediated chemotaxis by the lipid phosphatase activity of tumor suppressor PTEN SO BLOOD LA English DT Article ID SECONDARY LYMPHOID ORGANS; JURKAT T-CELLS; PHOSPHOINOSITIDE 3-KINASES; CHEMOKINE RECEPTORS; PROSTATE-CANCER; BREAST-CANCER; FACTOR-I; GENE; ACTIVATION; MIGRATION AB Phosphatase and tensin homolog deleted on chromosome 10 (PTEN), a multifunctional tumor suppressor, has been shown to play a regulatory role in cell migration. Dictyostelium discoideum cells lacking PTEN exhibited impaired migration toward chemoattractant gradients. In the present study, we investigated the involvement of PTEN in chemotaxis of mammalian cells by examining PTEN-null Jurkat T cells. We observed that, in contrast to observations made in D discoideum, PTEN-null Jurkat T cells exhibited potent chemotactic responses to the chemokine stromal cell-derived factor lot (SDF-1 alpha), indicating that PTEN was not requisite for CXC chemokine receptor 4 (CXCR4)-mediated chemotaxis of Jurkat cells. Conversely, reconstitution of PTEN in Jurkat cells by using a tetracycline (Tet-on)-inducible expression system down-regulated CXCR4-mediated chemotaxis. Furthermore, we established the lipid phosphatase activity of PTEN as essential for its inhibitory effect on chemotaxis. In addition, using PTEN-expressing T-cell lines and primary T cells, we demonstrated that down-regulation of PTEN expression with vector-based small interfering RNAs (siRNAs) enhanced CXCR4-mediated chemotaxis. Based on these results, we conclude that PTEN expression negatively regulates chemotaxis of lymphoid mammalian cells via its lipid phosphatase activity. Our findings may account for the reported increase in metastatic activity of PTEN-null tumor cells. C1 NCI Frederick, Mol Immunoregulat Lab, Ctr Canc Res, NIH, Frederick, MD 21702 USA. NIA, Dept Cellular & Mol Biol, NIH, Baltimore, MD 21224 USA. RP NCI Frederick, Mol Immunoregulat Lab, Ctr Canc Res, NIH, POB B,Bldg 560,Rm 31-19, Frederick, MD 21702 USA. EM howardz@mail.ncifcrf.gov RI Howard, O M Zack/B-6117-2012 OI Howard, O M Zack/0000-0002-0505-7052 NR 49 TC 31 Z9 33 U1 1 U2 9 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 EI 1528-0020 J9 BLOOD JI Blood PD OCT 15 PY 2005 VL 106 IS 8 BP 2619 EP 2626 DI 10.1182/blood-2004-08-3362 PG 8 WC Hematology SC Hematology GA 972PP UT WOS:000232466000013 PM 15994292 ER PT J AU Wlodarski, MW O'Keefe, C Howe, EC Risitano, AM Rodriguez, A Warshawsky, I Loughran, TP Maciejewski, JP AF Wlodarski, MW O'Keefe, C Howe, EC Risitano, AM Rodriguez, A Warshawsky, I Loughran, TP Maciejewski, JP TI Pathologic clonal cytotoxic T-cell responses: nonrandom nature of the T-cell-receptor restriction in large granular lymphocyte leukemia SO BLOOD LA English DT Article ID BONE-MARROW-TRANSPLANTATION; V-BETA REPERTOIRE; IN-VIVO; RHEUMATOID-ARTHRITIS; SJOGRENS-SYNDROME; APLASTIC-ANEMIA; FELTYS-SYNDROME; MULTIPLE-SCLEROSIS; JUNCTIONAL REGION; ANTIGEN RECEPTOR AB T-cell large granular lymphocyte (T-LGL) leukemia is a clonal lymphoproliferation of cytotoxic T cells (CTLs) associated with cytopenias. T-LGL proliferation seems to be triggered/sustained by antigenic drive; it is likely that hematopoietic progenitors are the targets in this process. The antigen-specific portion of the T-cell receptor (TCR), the variable beta (VB)-chain complementarity-determining region 3 (CDR3), can serve as a molecular signature (clonotype) of a T-cell clone. We hypothesized that clonal CTL proliferation develops not randomly but in the context of an autoimmune response. We identified the clonotypic sequence of T-LGL clones in 60 patients, including 56 with known T-LGL and 4 with unspecified neutropenia. Our method also allowed for the measurement of clonal frequencies; a decrease in or loss of the pathogenic clonotype and restoration of the TCR repertoire was found after hematologic remission. We identified 2 patients with identical immunodominant CDR3 sequence. Moreover, we found similarity between multiple immunodominant clonotypes and codominant as well as a nonexpanded, "supporting" clonotypes. The data suggest a nonrandom clonal selection in T-LGL, possibly driven by a common antigen. In contrast, the physiologic clonal CTL repertoire is highly diverse and we were not able to detect any significant clonal sharing in 26 healthy controls. C1 Cleveland Clin Fdn, Taussig Canc Ctr, Expt Hematol & Hematopoiesis Sect, Cleveland, OH 44195 USA. Cleveland Clin Fdn, Dept Clin Pathol, Cleveland, OH 44195 USA. Charite Med Sch, Inst Med Immunol, Berlin, Germany. Penn State Canc Inst, Hershey, PA USA. NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Maciejewski, JP (reprint author), Taussig Canc Ctr R40, 9500 Euclid Ave, Cleveland, OH 44195 USA. EM maciejj@ccf.org OI Wlodarski, Marcin/0000-0001-6638-9643 NR 83 TC 78 Z9 80 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD OCT 15 PY 2005 VL 106 IS 8 BP 2769 EP 2780 DI 10.1182/blood-2004-10-4045 PG 12 WC Hematology SC Hematology GA 972PP UT WOS:000232466000034 PM 15914562 ER PT J AU Rimoldi, M Chieppa, M Larghi, P Vulcano, M Allavena, P Rescigno, M AF Rimoldi, M Chieppa, M Larghi, P Vulcano, M Allavena, P Rescigno, M TI Monocyte-derived dendritic cells activated by bacteria or by bacteria-stimulated epithelial cells are functionally different SO BLOOD LA English DT Article ID SALMONELLA-TYPHIMURIUM; T-CELLS; CHEMOKINE RECEPTORS; IMMUNE-RESPONSES; INTESTINAL EPITHELIA; TOXOPLASMA-GONDII; CUTTING EDGE; IN-VIVO; INFECTION; FLAGELLIN AB Dendritic cells (DCs) are able to open the tight junctions between adjacent epithelial cells (ECs) and to take up both invasive and noninvasive bacteria directly from the intestinal lumen. In this study, we describe a tight cross talk between ECs and human monocyte-derived DCs (MoDCs) in bacterial handling across epithelial monolayers. We show that the release of proinflammatory mediators by ECs in response to bacteria is dependent on bacterial invasiveness and on the presence of flagella. This correlates with the capacity of EC-derived factors to modulate MoDC function. MoDCs incubated with supernatants of bacteria-treated ECs are "noninflammatory" as they release interleukin-10 (IL-10) but not IL-12 and can drive only T helper (Th)-2 type T cells. Moreover, noninflammatory MoDCs release chemokines aimed at recruiting Th2 and T-regulatory cells. In contrast, when MoDCs are incubated with ECs and bacteria in a transwell coculture system, and can contact directly the bacteria across stimulated EC monolayers, they are more inflammatory as they release IL-12 and IL-10 and induce both Th1 and Th2 responses. These results suggest that ECs are not simply a barrier to bacteria entering via the oral route, but they actively influence the activating properties of DCs. C1 European Inst Oncol, Dept Expt Oncol, Milan, Italy. Ist Ric Farmacol Mario Negri, Dept Immunol, Milan, Italy. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Rescigno, M (reprint author), Via Ripamonti 435, I-20141 Milan, Italy. EM maria.rescigno@ifom-ieo-campus.it RI Chieppa, Marcello/K-4846-2012; Rescigno, Maria/J-9704-2012; Larghi, Paola/K-6061-2016; OI Rescigno, Maria/0000-0002-6464-509X; Larghi, Paola/0000-0001-7074-1590; Chieppa, Marcello/0000-0001-9819-0823 NR 47 TC 110 Z9 116 U1 0 U2 8 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD OCT 15 PY 2005 VL 106 IS 8 BP 2818 EP 2826 DI 10.1182/blood-2004-11-4321 PG 9 WC Hematology SC Hematology GA 972PP UT WOS:000232466000040 PM 16030185 ER PT J AU Gotlib, J Berube, C Growney, JD Chen, CC George, TI Williams, C Kajiguchi, T Ruan, J Lilleberg, SL Durocher, JA Lichy, JH Wang, YF Cohen, PS Arber, DA Heinrich, MC Neckers, L Galli, SJ Gilliland, DG Coutre, SE AF Gotlib, J Berube, C Growney, JD Chen, CC George, TI Williams, C Kajiguchi, T Ruan, J Lilleberg, SL Durocher, JA Lichy, JH Wang, YF Cohen, PS Arber, DA Heinrich, MC Neckers, L Galli, SJ Gilliland, DG Coutre, SE TI Activity of the tyrosine kinase inhibitor PKC412 in a patient with mast cell leukemia with the D816V KIT mutation SO BLOOD LA English DT Article ID PROTOONCOGENE C-KIT; SYSTEMIC MASTOCYTOSIS; ACTIVATING MUTATION; WILD-TYPE; IMATINIB; PROTEIN; IDENTIFICATION; RESISTANT; DISORDER; DISEASE AB The majority of patients with systemic mast cell disease express the imatinib-resistant Asp816Val (D816V) mutation in the KIT receptor tyrosine kinase. Limited treatment options exist for aggressive systemic mastocytosis (ASM) and mast cell leukemia (MCL). We evaluated whether PKC412, a small-molecule inhibitor of KIT with a different chemical structure from imatinib, may have therapeutic use in advanced SM with the D816V KIT mutation. We treated a patient with MCL (with an associated myelodysplastic syndrome (MDS)/myeloproliferative disorder [MPD]) based on in vitro studies demonstrating that PKC412 could inhibit D816V KIT-transformed Ba/F3 cell growth with a 50% inhibitory concentration (IC50) of 30 nM to 40 nlM. The patient exhibited a partial response with significant resolution of liver function abnormalities. In addition, PKC412 treatment resulted in a significant decline in the percentage of peripheral blood mast cells and serum histamine level and was associated with a decrease in KIT phosphorylation and D816V KIT mutation frequency. The patient died after 3 months of therapy due to progression of her MDS/MPD to acute myeloid leukemia (AML). This case indicates that KIT tyrosine kinase inhibition is a feasible approach in SM, but single-agent clinical efficacy may be limited by clonal evolution in the advanced leukemic phase of this disease. C1 Stanford Univ, Sch Med, Dept Med, Div Hematol, Stanford, CA 94305 USA. Brigham & Womens Hosp, Dept Med, Div Hematol, Boston, MA 02115 USA. Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA. NCI, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. Transgenomic, Gaithersburg, MD USA. Armed Forces Inst Pathol, Dept Mol Pathol, Washington, DC 20306 USA. Novartis Pharmaceut, E Hanover, NJ USA. Oregon Hlth & Sci Univ, Inst Canc, Portland VA Med Ctr, Portland, OR USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Gotlib, J (reprint author), Stanford Canc Ctr, 875 Blake Wilbur Dr,Rm 2327B, Stanford, CA 94305 USA. EM jason.gotlib@stanford.edu RI Chen, Ching-Cheng/C-1259-2009; OI Chen, Ching-Cheng/0000-0003-4499-0889 FU NCI NIH HHS [CA-72074, CA66996]; NHLBI NIH HHS [K23HL04409]; NIAID NIH HHS [AI-41995, AI-23990]; NIDDK NIH HHS [DK50654] NR 29 TC 152 Z9 155 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD OCT 15 PY 2005 VL 106 IS 8 BP 2865 EP 2870 DI 10.1182/blood-2005-04-1568 PG 6 WC Hematology SC Hematology GA 972PP UT WOS:000232466000047 PM 15972446 ER PT J AU Elshal, MF Khan, SS Takahashi, Y Solomon, MA McCoy, JP AF Elshal, MF Khan, SS Takahashi, Y Solomon, MA McCoy, JP TI CD146 (Mel-CAM), an adhesion marker of endothelial cells, is a novel marker of lymphocyte subset activation in normal peripheral blood SO BLOOD LA English DT Letter C1 NHLBI, Bethesda, MD 20892 USA. RP McCoy, JP (reprint author), NHLBI, Bldg 10,Rm 4A07,10 Ctr Dr,MSC 1357, Bethesda, MD 20892 USA. EM mccoyjp@mail.nih.gov RI Elshal, Mohamed/H-7953-2012; Takahashi, Yoshiyuki/I-1929-2012 NR 5 TC 70 Z9 75 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD OCT 15 PY 2005 VL 106 IS 8 BP 2923 EP 2924 DI 10.1182/blood-2005-06-2307 PG 2 WC Hematology SC Hematology GA 972PP UT WOS:000232466000058 PM 16204154 ER PT J AU Skjaerven, R Vatten, LJ Wilcox, AJ Ronning, T Irgens, LM Lie, RT AF Skjaerven, R Vatten, LJ Wilcox, AJ Ronning, T Irgens, LM Lie, RT TI Recurrence of pre-eclampsia across generations: exploring fetal and maternal genetic components in a population based cohort SO BRITISH MEDICAL JOURNAL LA English DT Article ID RISK-FACTORS; GESTATIONAL HYPERTENSION; ABRUPTIO PLACENTAE; ECLAMPSIA; FAMILY; PREDISPOSITION; PREGNANCIES; MORTALITY; GROWTH; WOMEN AB Objectives To assess the impact on risk of pre-eclampsia of genes that work through the mother, and genes of paternal origin that work through the fetus. Design Population based cohort study. Setting Registry data from Norway. Participants Linked generational data from the medical birth registry of Norway (1967-2003): 438 597 mother-offspring units and 286 945 father-offspring units. Main outcome measures Pre-eclampsia in the second generation. Results The daughters of women who had pre-eclampsia during pregnancy had more than twice the risk of pre-eclampsia themselves (odds ratio 2.2, 95% confidence interval 2.0 to 2.4) compared with other women. Men born after a pregnancy complicated by pre-eclampsia had a moderately increased risk of fathering a pre-eclamptic pregnancy (1.5, 1.3 to 1.7). Sisters of affected men or women who were themselves born after pregnancies not complicated by pre-eclampsia, also had an increased risk (2.0, 1.7 to 2.3). Women and men born after pre-eclamptic pregnancies were more likely to trigger severe pre-eclampsia in their own pregnancy (3.0, 2.4 to 3.7, for mothers and 1.9, 1.4 to 2.5, for fathers). Conclusion Maternal genes and fetal genes from either the mother or father may trigger pre-eclampsia. The maternal association is stronger than the fetal association. The familial association predicts more severe pre-eclampsia. C1 Univ Bergen, Dept Publ Hlth & Primary Hlth Care, Sect Epidemiol & Med Stat, N-5020 Bergen, Norway. Norwegian Univ Sci & Technol, Fac Med, N-7034 Trondheim, Norway. NIEHS, Res Triangle Pk, NC 27709 USA. Norwegian Inst Publ Hlth, Div Genes & Environm, Oslo, Norway. Norwegian Inst Publ Hlth, Med Birth Registry Norway, Bergen, Norway. RP Skjaerven, R (reprint author), Univ Bergen, Dept Publ Hlth & Primary Hlth Care, Sect Epidemiol & Med Stat, N-5020 Bergen, Norway. EM Rolv.Skjaerven@smis.uib.no OI Wilcox, Allen/0000-0002-3376-1311 NR 25 TC 123 Z9 125 U1 2 U2 4 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0959-8146 J9 BRIT MED J JI Br. Med. J. PD OCT 15 PY 2005 VL 331 IS 7521 BP 877 EP 879 DI 10.1136/bmj.38555.462685.8F PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 975SX UT WOS:000232683300021 PM 16169871 ER PT J AU Prout, GR Wesley, MN Yancik, R Ries, LAG Havlik, RJ Edwards, BK AF Prout, GR Wesley, MN Yancik, R Ries, LAG Havlik, RJ Edwards, BK TI Age and Comorbidity impact surgical therapy in older bladder carcinoma patients - A population-based study SO CANCER LA English DT Article DE invasive bladder carcinoma; surgical therapy; age; American Society of Anesthesiologists physical status classification; cystectomy; SEER; comorbidity ID RADICAL CYSTECTOMY; ELDERLY-PATIENTS; CANCER; COMPLICATIONS; CISPLATIN; SURVIVAL; CARE; EXPERIENCE; RADIATION; PATTERNS AB BACKGROUND. Bladder carcinoma often occurs in older patients who also may have other comorbid conditions that could influence the administration of surgical therapy. The current study was conducted to describe the distribution of comorbid conditions in patients with bladder carcinoma and ascertain whether these con- ditions, as grouped by the American Society of Anesthesiologists physical status classification, affected the choice of surgical therapy. METHODS. The authors examined six population-based cancer registries from the National Cancer Institute's Surveillance, Epidemiology, and End Results Program in 1992. A total of 820 individuals age 55 years and older was found. A random sample of newly diagnosed bladder carcinoma patients were stratified according to registry, age group (ages 55-64 yrs, ages 65-74 yrs, and age 75 yrs and older), and gender. Data regarding comorbid conditions were abstracted from the medical records and merged with routinely collected cancer registry data. The main out- come measures were the prevalence and distribution of comorbid conditions, American Society of Anesthesiologists physical status classification, and the receipt of cystectomy in patients with muscle invasion. RESULTS. Hypertension, chronic pulmonary disease, arthritis, and heart disease were found to affect at least 15% of the study population. Approximately 38% of patients were current or former smokers. Greater than 90% of patients with superficial disease were treated with transurethral resection alone. Among those patients with muscle invasion, only 55% of those ages 55-59 years underwent cystectomy; this percentage dropped to 4% in patients age 85 years and older. Among patients with an American Society of Anesthesiologists physical status classification of 0-2, the cystectomy rate ranged from 53% in those ages 55-59 years to 9% in those age 85 years and older. CONCLUSIONS. There were no significant treatment differences noted with regard to age among patients with superficial disease. Among those patients with muscle invasion, those age 75 years and older were less likely to undergo radical cysteclance, tomy (14%) compared with patients ages 55-64 years (48%) and those ages 65-74 years (43%). Patient age may contribute to treatment decisions in patients with muscle-invasive disease, even when comorbidity is taken into account. C1 NCI, Surveillance Res Program, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Serv Urol, Boston, MA 02114 USA. Informat Management Serv Inc, Silver Spring, MD USA. NIA, Canc Sect, Geriatr Program, NIH, Bethesda, MD 20892 USA. NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA. NCI, Surveillance Res Program, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. RP Edwards, BK (reprint author), NCI, Surveillance Res Program, Div Canc Control & Populat Sci, NIH, 6116 Execut Blvd,Suite 504, Bethesda, MD 20892 USA. EM edwardsb@mail.nih.gov NR 34 TC 100 Z9 100 U1 2 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD OCT 15 PY 2005 VL 104 IS 8 BP 1638 EP 1647 DI 10.1002/cncr.21354 PG 10 WC Oncology SC Oncology GA 973FM UT WOS:000232508300012 PM 16130136 ER PT J AU Anderson, WF Devesa, SS AF Anderson, WF Devesa, SS TI In situ male breast carcinoma in the surveillance, epidemiology, and end results database of the National Cancer Institute SO CANCER LA English DT Article DE male breast carcinoma; cancer in situ; hormone receptor expression; prognostic factors ID AGE DISTRIBUTION; HISTOLOGIC TYPES; RISK-FACTORS; PATTERNS; RATES; MEN AB BACKGROUND. In situ breast carcinoma is not so well characterized for men as for women. METHODS. Therefore, the authors of the current study compared male and female in situ and invasive breast carcinomas in the Surveillance, Epidemiology, and End Results (SEER) database of the National Cancer Institute to document these patterns. RESULTS. In situ breast carcinomas composed 9.4% of all male (n = 280 of 2984) and 11.9% of all female breast carcinomas (n = 53,928 of 454,405) during the years 1973-2001. In situ rates rose 123% for men and 555% for women over this time period; whereas distant disease rates fell for both genders. Median ages at diagnosis were 62 years for in situ and 68 years for invasive breast carcinoma among men, compared with 58 years for in situ and 62 years for invasive breast carcinoma among women. Papillary in situ and invasive architectural types were more common among men than Women. In contrast, lobular tumors were more common among women than men. Breast cancer-specific survival was similar among men and women, whereas overall survival was worse for men than women. CONCLUSION. in situ male breast carcinoma is a rare disease, occurring at older ages and with different architectural types than its more common female counterpart. Gender-specific histopathologic differences probably reflect anatomic differences among the normal female and vestigial male breast. Rising in situ male breast carcinoma incidence rates over the past three decades suggest earlier detection over time, irrespective of mammography, because men do not participate in routine screening mammography. Worse overall survival for men than women possibly results from age-dependent comorbid illnesses. C1 NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. RP Anderson, WF (reprint author), NCI, Dept Hlth & Human Resources, EPS, NIH, Suite 8036,6120 Execut Blvd, Rockville, MD 20852 USA. EM wanderso@mail.nih.gov FU Intramural NIH HHS NR 30 TC 22 Z9 22 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD OCT 15 PY 2005 VL 104 IS 8 BP 1733 EP 1741 DI 10.1002/cncr.21353 PG 9 WC Oncology SC Oncology GA 973FM UT WOS:000232508300025 PM 16138363 ER PT J AU Sogn, JA Anton-Culver, H Singer, DS AF Sogn, JA Anton-Culver, H Singer, DS TI Meeting report: NCI think tanks in cancer biology SO CANCER RESEARCH LA English DT Editorial Material AB Over the past year and a half, the Division of Cancer Biology of NCI has been assessing the state of cancer biology, with the goal of developing a research agenda for the near future that would accelerate progress in cancer research. Our goal was to identify emerging concepts and promising opportunities for investigation across nine scientific areas with unusual promise for rapid progress. A series of meetings called Think Tanks was convened, each involving a panel of 15-25 experts. In all, over 160 leaders in cancer research and related fields discussed the current state of science in their disciplines, projected its trajectory and recommended what NCI could or should do to facilitate progress. In addition to emphasizing the importance of continued support for investigator-initiated research, the Think Tanks permitted identification of a number of overarching themes. Critical among them was the need to support the development of integrative cancer biology and to encourage studies of the tumor microenvironment by establishing an infrastructure for interactive research. There was also consensus about the importance of comparative studies of normal and tumor states, and development of mechanisms for supporting collaborative, interdisciplinary research and training. C1 NCI, Div Canc Biol, Bethesda, MD 20892 USA. Univ Calif Irvine, Sch Med, Div Epidemiol, Irvine, CA 92717 USA. RP Sogn, JA (reprint author), NCI, Div Canc Biol, 301 Pl N,Room 5050,6130 Execut Blvd, Bethesda, MD 20892 USA. EM js150x@nih.gov NR 0 TC 10 Z9 11 U1 0 U2 1 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 15 PY 2005 VL 65 IS 20 BP 9117 EP 9120 DI 10.1158/0008-5472.CAIN-05-1817 PG 4 WC Oncology SC Oncology GA 974BR UT WOS:000232566800003 PM 16230364 ER PT J AU Ying, L Marino, J Hussain, SP Khan, MA You, SJ Hofseth, AB Trivers, GE Dixon, DA Harris, CC Hofseth, LJ AF Ying, L Marino, J Hussain, SP Khan, MA You, SJ Hofseth, AB Trivers, GE Dixon, DA Harris, CC Hofseth, LJ TI Chronic inflammation promotes retinoblastoma protein hyperphosphorylation and E2F1 activation SO CANCER RESEARCH LA English DT Article ID ULCERATIVE-COLITIS; CELL-CYCLE; EPITHELIAL PROLIFERATION; CANCER; PHOSPHORYLATION; P53; EXPRESSION; GENE; RB; INSTABILITY AB Chronic inflammation contributes to tumorigenesis. The retinoblastoma protein (pRb), in its hyperphosphorylated form, releases E2 promoter binding factor-1 (E2F1), which drives cell proliferation. Here, we show that pRb is hyperphosphorylated in both mouse and human colitis. In turn, pRb hyperphosphorylation is associated with release of E2F1 from pRb, resulting in the activation of E2F1 target molecules involved in proliferation and apoptosis. These observations provide insight into the in vivo mechanisms associated with chronic colon inflammation and increased colon cancer risk. C1 Univ S Carolina, Coll Pharm, Dept Basic Pharmaceut Sci, Lab Inflammatory Driven Carcinogenesis, Columbia, SC 29208 USA. Univ S Carolina, Dept Biol Sci, Columbia, SC 29208 USA. Univ S Carolina, WJB Dorn Vet Affairs Med Ctr, Columbia, SC 29208 USA. Univ S Carolina, Sch Med, Columbia, SC 29208 USA. Natl Canc Inst, Human Carcinogenesis Lab, NIH, Bethesda, MD USA. RP Hofseth, LJ (reprint author), Univ S Carolina, Coll Pharm, Dept Basic Pharmaceut Sci, Lab Inflammatory Driven Carcinogenesis, Coker Life Sci,Room 513C,770 Sumter St, Columbia, SC 29208 USA. EM hofseth@cop.sc.edu FU NCRR NIH HHS [P20 RR17698-01] NR 28 TC 34 Z9 35 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 15 PY 2005 VL 65 IS 20 BP 9132 EP 9136 DI 10.1158/0008-5472.CAN-05-1358 PG 5 WC Oncology SC Oncology GA 974BR UT WOS:000232566800006 PM 16230367 ER PT J AU Baird, K Davis, S Antonescu, CR Harper, UL Walker, RL Chen, YD Glatfelter, AA Duray, PH Meltzer, PS AF Baird, K Davis, S Antonescu, CR Harper, UL Walker, RL Chen, YD Glatfelter, AA Duray, PH Meltzer, PS TI Gene expression profiling of human sarcomas: Insights into sarcoma biology SO CANCER RESEARCH LA English DT Article ID SOFT-TISSUE TUMORS; GASTROINTESTINAL STROMAL TUMORS; MALIGNANT FIBROUS HISTIOCYTOMAS; PLASMINOGEN-ACTIVATOR SYSTEM; GROWTH-FACTOR RECEPTOR; DERMATOFIBROSARCOMA PROTUBERANS; CDNA MICROARRAYS; SYNOVIAL SARCOMA; CANCER; PROTEIN AB Sarcomas are a biologically complex group of tumors of mesenchymal origin. By using gene expression microarray analysis, we aimed to find clues into the cellular differentiation and oncogenic pathways active in these tumors as well as potential biomarkers and therapeutic targets. We examined 181 tumors representing 16 classes of human bone and soft tissue sarcomas on a 12,601-feature cDNA microarray. Remarkably, 2,766 probes differentially expressed across this sample set clearly delineated the various tumor classes. Several genes of potential biological and therapeutic interest were associated with each sarcoma type, including specific tyrosine kinases, transcription factors, and homeobox genes. We also identified subgroups of tumors within the liposarcomas, leiomyosarcomas, and malignant fibrous histiocytomas. We found significant gene ontology correlates for each tumor group and identified similarity to normal tissues by Gene Set Enrichment Analysis. Mutation analysis done on 275 tumor samples revealed that the high expression of epidermal growth factor receptor (EGFR) in certain tumors was not associated with gene mutations. Finally, to further the investigation of human sarcoma biology, we have created an online, publicly available, searchable database housing the data from the gene expression profiles of these tumors (http://watson.nhgri.nih.gov/sarcoma), allowing the user to interactively explore this data set in depth. C1 NHGRI, Canc Genet Branch, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. RP Meltzer, PS (reprint author), NHGRI, NIH, 50 S Dr, Bethesda, MD 20892 USA. EM pmeltzer@mail.nih.gov OI Davis, Sean/0000-0002-8991-6458 NR 56 TC 188 Z9 199 U1 0 U2 9 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 15 PY 2005 VL 65 IS 20 BP 9226 EP 9235 DI 10.1158/0008-5472.CAN-05-1699 PG 10 WC Oncology SC Oncology GA 974BR UT WOS:000232566800022 PM 16230383 ER PT J AU Nagl, NG Patsialou, A Haines, DS Dallas, PB Beck, GR Moran, E AF Nagl, NG Patsialou, A Haines, DS Dallas, PB Beck, GR Moran, E TI The p270 (ARID1A/SMARCF1) subunit of mammalian SWI/SNF-related complexes is essential for normal cell cycle arrest SO CANCER RESEARCH LA English DT Article ID CHROMATIN-REMODELING COMPLEX; ATYPICAL TERATOID/RHABDOID TUMORS; MALIGNANT RHABDOID TUMORS; SWI-SNF COMPLEX; RETINOBLASTOMA PROTEIN; TRANSCRIPTION FACTORS; HSNF5/INI1 GENE; MC3T3-E1 CELLS; LUNG-CANCER; DIFFERENTIATION AB Mammalian SWI/SNF-related complexes are ATPase-powered nucleosome remodeling assemblies crucial for proper development and tissue-specific gene expression. The ATPase activity of the complexes is also critical for tumor suppression. The complexes contain seven or more noncatalytic subunits; only one of which, hSNF5/Ini1/BAF47, has been individually identified as a tumor suppressor thus far. The noncatalytic subunits include p270/ARID1A, which is of particular interest because tissue array analysis corroborated by screening of tumor cell lines indicates that p270 may be deficient in as many as 30% of renal carcinomas and 10% of breast carcinomas. The complexes can also include an alternative ARID1B subunit, which is closely related to p270, but the product of an independent gene. The respective importance of p270 and ARID1B in the control of cell proliferation was explored here using a short interfering RNA approach and a cell system that permits analysis of differentiation-associated cell cycle arrest. The p270-depleted cells fail to undergo normal cell cycle arrest on induction, as evidenced by continued synthesis of DNA. These lines fail to show other characteristics typical of arrested cells, including up-regulation of p21 and down-regulation of cyclins. The requirement for p270 is evident separately in both the up-regulation of p21 and the down-regulation of E2F-responsive products. In contrast, the ARID1B-depleted lines behaved like the parental cells in these assays. Thus, p270-containing complexes are functionally distinct from ARID1B-containing complexes. These results provide a direct biological basis to support the implication from tumor tissue screens that deficiency of p270 plays a causative role in carcinogenesis. C1 Temple Univ, Sch Med, Fels Inst Canc Res & Mol Biol, Philadelphia, PA 19140 USA. NCI, Lab Canc Prevent, Frederick, MD 21701 USA. RP Moran, E (reprint author), Temple Univ, Sch Med, Fels Inst Canc Res & Mol Biol, Philadelphia, PA 19140 USA. EM betty@temple.edu RI Dallas, Peter/C-4695-2013 OI Dallas, Peter/0000-0003-0861-9054 FU NCI NIH HHS [1R24CA88261, R01CA53592] NR 54 TC 56 Z9 58 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 15 PY 2005 VL 65 IS 20 BP 9236 EP 9244 DI 10.1158/0008-5472.CAN-05-1225 PG 9 WC Oncology SC Oncology GA 974BR UT WOS:000232566800023 PM 16230384 ER PT J AU Chen, KG Wang, YC Schaner, ME Francisco, B Duran, GE Juric, D Huff, LM Padilla-Nash, H Ried, T Fojo, T Sikic, BI AF Chen, KG Wang, YC Schaner, ME Francisco, B Duran, GE Juric, D Huff, LM Padilla-Nash, H Ried, T Fojo, T Sikic, BI TI Genetic and epigenetic modeling of the origins of multidrug-resistant cells in a human sarcoma cell line SO CANCER RESEARCH LA English DT Article ID MDR1 GENE; P-GLYCOPROTEIN; TRANSCRIPTIONAL REGULATION; MUTATION-RATE; ACTIVATION; CANCER; TRANSPORTERS; SENSITIVITY; DOXORUBICIN; MECHANISMS AB The origin of drug-resistant cells in human cancers has been a fundamental problem of cancer pharmacology. Two major contrasting hypotheses (genetics versus epigenetics) have been proposed to elucidate the mechanisms of acquired drug resistance. In this study, we answer these fundamental questions through investigation of the genetic and epigenetic pathways that control the origin of ABCB1 (MDR1) gene activation with acquired multidrug resistance in drug-sensitive human sarcoma (MES-SA cells). The genetic and epigenetic bases of this selected activation involve the initiation of transcription at a site 112 kb upstream of the ABCB1 proximal promoter (PI) in the drug-resistant cells. This activation was associated with a chromatin-remodeling process characterized by an increase in acetylated histone H3 within a 968-bp region 5' of the ABCB1 upstream promoter. These alterations provide both genetic and epigenetic susceptibility for ABCB1 expression in drug-resistant cells. Complete activation of the ABCB1 gene through the coding region was proposed by interactions of selected trans-alterations or epigenetic changes on the ABCB-1 proximal promoter, which occurred during initial drug exposure. Thus, our data provide evidence for a major genomic alteration that changes the chromatin structure of the ABCB1 upstream promoter via acetylation of histone H3 initiating ABCB1 activation, further elucidating the genetic and epigenetic bases that determine chemotherapeutic response in drug-resistant derivatives of MES-SA cells. C1 NINDS, NIH, Stem Cell Unit, Genet Branch,Natl Canc Inst, Bethesda, MD 20892 USA. Stanford Univ, Sch Med, Div Oncol, Dept Med, Stanford, CA 94305 USA. Stanford Univ, Sch Med, Program Canc Biol, Stanford, CA 94305 USA. RP Chen, KG (reprint author), NINDS, NIH, Stem Cell Unit, Genet Branch,Natl Canc Inst, Room 1000,Bldg 37,Convent Dr, Bethesda, MD 20892 USA. EM cheng@mail.nih.gov RI Juric, Dejan/C-5214-2008; Chen, Kevin/D-6769-2011 OI Chen, Kevin/0000-0003-2983-6330 FU Intramural NIH HHS [Z99 NS999999]; NCI NIH HHS [CA09302, R01-CA92474] NR 23 TC 27 Z9 33 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 15 PY 2005 VL 65 IS 20 BP 9388 EP 9397 DI 10.1158/0008-5472.CAN-04-4133 PG 10 WC Oncology SC Oncology GA 974BR UT WOS:000232566800041 PM 16230402 ER PT J AU Zheng, YL Loffredo, CA Alberg, AJ Yu, ZP Jones, RT Perlmutter, D Enewold, L Krasna, MJ Yung, R Shields, PG Harris, CC AF Zheng, YL Loffredo, CA Alberg, AJ Yu, ZP Jones, RT Perlmutter, D Enewold, L Krasna, MJ Yung, R Shields, PG Harris, CC TI Less efficient G(2)-M checkpoint is associated with an increased risk of lung cancer in African Americans SO CANCER RESEARCH LA English DT Article ID CELL-CYCLE CHECKPOINTS; WILD-TYPE P53; ATAXIA-TELANGIECTASIA; MUTAGEN SENSITIVITY; DNA-DAMAGE; CHROMOSOMAL-ABERRATIONS; CHROMATID DAMAGE; X-IRRADIATION; BREAST-CANCER; GENE AB Cell cycle checkpoints play critical roles in the maintenance of genomic integrity. The inactivation of checkpoint genes by genetic and epigenetic mechanisms is frequent in all cancer types, as a less-efficient cell cycle control can lead to genetic instability and tumorigenesis. In an on-going case-control study consisting of 216 patients with non-small cell lung cancer, 226 population-based controls, and 114 hospital-based controls, we investigated the relationship of gamma-radiation-induced G(2)-M arrest and lung cancer risk. Peripheral blood lymphocytes were cultured for 90 hours, exposed to 1.0 G gamma gamma-radiation, and harvested at 3 hours after gamma-radiation treatment. gamma-Radiation-induced G(2)-M arrest was measured as the percentage of mitotic cells in untreated cultures minus the percentage of mitotic cells in gamma-radiation-treated cultures from the same subject. The mean percentage of gamma-radiation-induced G2-M arrest was significantly lower in cases than in population controls (1.18 versus 1.44, P < 0.01) and hospital controls (1.18 versus 1.40, P = 0.01). When dichotomized at the 50th percentile value in combined controls (population and hospital controls), a lower level of gamma-radiation-induced G(2)-M arrest was associated with an increased risk of lung cancer among African Americans after adjusting for baseline mitotic index, age, gender, and pack-years of smoking [adjusted odd ratio (OR), 2.25; 95% confidence interval (95% CI), 0.97-5.20]. A significant trend of an increased risk of lung cancer with a decreased level of G(2)-M arrest was observed (P-trend = 0.02) among African Americans, with a lowest-versus-highest quartile adjusted OR of 3.74 (95% Cl, 0.98-14.3). This trend was most apparent among African American females (P-trend < 0.01), with a lowest-versus-highest quartile adjusted OR of 11.75 (95% Cl, 1.47-94.04). The results suggest that a less-efficient DNA damage-induced G(2)-M checkpoint is associated with an increased risk of lung cancer among African Americans. Interestingly, we observed a stronger association of DNA damage-induced G(2)-M arrest and lung cancer among African Americans when compared with Caucasians. If replicated, these results may provide clues to the exceedingly high lung cancer incidence experienced by African Americans. C1 NCI, Human Carcinogenesis Lab, Canc Res Ctr, Bethesda, MD 20892 USA. Georgetown Univ, Canc Genet & Epidemiol Program, Washington, DC USA. Univ Maryland, Sch Med, Johns Hopkins Med Inst, Dept Epidemiol, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Johns Hopkins Med Inst, Dept Pulm Med, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Greenbaum Canc Ctr, Dept Pathol & Surg, Baltimore, MD 21201 USA. RP Harris, CC (reprint author), NCI, Human Carcinogenesis Lab, Canc Res Ctr, 37 Convent Dr,Bldg 37,Room 3068, Bethesda, MD 20892 USA. EM curtis_harris@nih.gov RI Shields, Peter/I-1644-2012 FU NCI NIH HHS [CA73790, Z01 BC005480-20] NR 53 TC 32 Z9 32 U1 0 U2 3 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 15 PY 2005 VL 65 IS 20 BP 9566 EP 9573 DI 10.1158/0008-5472.CAN.05-1003 PG 8 WC Oncology SC Oncology GA 974BR UT WOS:000232566800061 PM 16230422 ER PT J AU Lan, Q Zhang, LP Shen, M Smith, MT Li, GL Vermeulen, R Rappaport, SM Forrest, MS Hayes, RB Linet, M Dosemeci, M Alter, BP Weinberg, RS Yin, SN Yeager, M Welch, R Waidyanatha, S Kim, SK Chanock, S Rothman, N AF Lan, Q Zhang, LP Shen, M Smith, MT Li, GL Vermeulen, R Rappaport, SM Forrest, MS Hayes, RB Linet, M Dosemeci, M Alter, BP Weinberg, RS Yin, SN Yeager, M Welch, R Waidyanatha, S Kim, SK Chanock, S Rothman, N TI Polymorphisms in cytokine and cellular adhesion molecule genes and susceptibility to hematotoxicity among workers exposed to benzene SO CANCER RESEARCH LA English DT Article ID PERIPHERAL-BLOOD CELLS; BONE-MARROW; PROMOTER HAPLOTYPES; METABOLITE HYDROQUINONE; INTERLEUKIN-10 GENE; REACTIVE METABOLITE; ALZHEIMERS-DISEASE; PROGENITOR CELLS; B-LYMPHOPOIESIS; RISK-FACTOR AB Benzene is a recognized hematotoxin and leukemogen but its mechanism of action and the role of genetic susceptibility are still unclear. Cytokines, chemokines, and cellular adhesion molecules are soluble proteins that play an important regulatory role in hematopoiesis. We therefore hypothesized that variation in these genes could influence benzene-induced hematotoxicity. We analyzed common, well-studied single-nucleotide polymorphisms (SNPs) in 20 candidate genes drawn from these pathways in a study of 250 workers exposed to benzene and 140 unexposed controls in China. After accounting for multiple comparisons, SNPs in five genes were associated with a statistically significant decrease in total WBC counts among exposed workers [IL-1A (-889C > T), IL-4 (-1098T > G), IL-10 (-819T > C), IL-12A (8685G > A), and VCAM1 (-1591T > C)], and one SNP [CSF3 (Ex4-165C > T)] was associated with an increase in WBC counts. The adhesion molecule VCAM1 variant was particularly noteworthy as it was associated with a decrease in B cells, natural killer cells, CD4(+) T cells, and monocytes. Further, VCAM1 (-1591T > C) and CSF3 (Ex4-165C > T) were associated, respectively, with decreased (P = 0.041) and increased (P = 0.076) CFU-GEMM progenitor cell colony formation in 29 benzene-exposed workers. This is the first report to provide evidence that SNPs in genes that regulate hematopoiesis influence benzene-induced hematotoxicity. C1 NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NCI, NIH, Canc Res Ctr, Bethesda, MD 20892 USA. Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. Chinese Ctr Dis Control & Prevent, Beijing, Peoples R China. Univ N Carolina, Sch Publ Hlth, Chapel Hill, NC USA. New York Blood Ctr, Clin Serv, White Plains, NY USA. RP Lan, Q (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, MSC 7240,6120 Execut Blvd,EPS 8109, Bethesda, MD 20892 USA. EM qingl@mail.nih.gov RI Vermeulen, Roel/F-8037-2011; OI Vermeulen, Roel/0000-0003-4082-8163; Hayes, Richard/0000-0002-0918-661X; Forrest, Matthew/0000-0002-2141-0303 FU NIEHS NIH HHS [P30ES01896, P30ES10126, P42ES04705, P42ES05948, R01ES06721] NR 55 TC 41 Z9 44 U1 0 U2 1 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 15 PY 2005 VL 65 IS 20 BP 9574 EP 9581 DI 10.1158/0008-5472.CAN-05-1419 PG 8 WC Oncology SC Oncology GA 974BR UT WOS:000232566800062 PM 16230423 ER PT J AU Cocco, P Fadda, D Billai, B D'Atri, M Melis, M Blair, A AF Cocco, P Fadda, D Billai, B D'Atri, M Melis, M Blair, A TI Cancer mortality among men occupationally exposed to dichlorodiphenyltrichloroethane SO CANCER RESEARCH LA English DT Article ID NON-HODGKINS-LYMPHOMA; PANCREATIC-CANCER; UNITED-STATES; ENVIRONMENTAL EXPOSURE; AGRICULTURAL HEALTH; GASTRIC-CANCER; BREAST-CANCER; RISK-FACTORS; DDT; WORKERS AB Several studies have evaluated cancer risk associated with occupational and environmental exposure to dichlorodiphenyltrichloroethane (DDT). Results are mixed. To further inquire into human carcinogenicity of DDT, we conducted a mortality follow-up study of 4,552 male workers, exposed to DDT during antimalarial operations in Sardinia, Italy, conducted in 1946 to 1950. Detailed information on DDT use during the operations provided the opportunity to develop individual estimates of average and cumulative exposure. Mortality of the cohort was first compared with that of the Sardinian population. Overall mortality in the cohort was about as expected, but there was a deficit for death from cardiovascular disease and a slight excess for nonmalignant respiratory diseases and lymphatic cancer among the unexposed subcohort. For internal comparisons, we used Poisson regression analysis to calculate relative risks of selected malignant and nonmalignant diseases with the unexposed subcohort as the reference. Cancer mortality was decreased among DDT-exposed workers, mainly due to a reduction in lung cancer deaths. Birth outside from the study area was a strong predictor of mortality from leukemia. Mortality from stomach cancer increased up to 2-fold in the highest quartile of cumulative exposure (relative risk, 2.0; 95% confidence interval, 0.9-4.4), but no exposure-response trend was observed. Risks of liver cancer, pancreatic cancer, and leukemia were not elevated among DDT-exposed workers. No effect of latency on risk estimates was observed over the 45 years of follow-up and within selected time windows. Adjusting risks by possible exposure to chlordane in the second part of the antimalarial operations did not change the results. In conclusion, we found little evidence for a link between occupational exposure to DDT and mortality from any of the cancers previously suggested to be associated. C1 Univ Cagliari, Dept Publ Hlth, Occupat Hlth Sect, I-09124 Cagliari, Italy. NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Cocco, P (reprint author), Univ Cagliari, Dept Publ Hlth, Occupat Hlth Sect, I-09124 Cagliari, Italy. EM coccop@pacs.unica.it FU NCI NIH HHS [Z01 CP010120-10] NR 35 TC 29 Z9 32 U1 2 U2 3 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 15 PY 2005 VL 65 IS 20 BP 9588 EP 9594 DI 10.1158/0008-5472.CAN-05-1487 PG 7 WC Oncology SC Oncology GA 974BR UT WOS:000232566800064 PM 16230425 ER PT J AU Bates, SE Fojo, T AF Bates, SE Fojo, T TI Epidermal growth factor receptor inhibitors: A moving target? SO CLINICAL CANCER RESEARCH LA English DT Editorial Material ID CELL LUNG-CANCER; TYROSINE KINASE INHIBITOR; METASTATIC BREAST-CANCER; PHASE-II; COLORECTAL-CANCER; INTRON 1; GEFITINIB; ERLOTINIB; MUTATIONS; GENE C1 NCI, Ctr Canc Res, Bethesda, MD 20892 USA. RP Bates, SE (reprint author), NCI, Ctr Canc Res, Bldg 10,Room 12N226, Bethesda, MD 20892 USA. EM sebates@helix.nih.gov NR 33 TC 12 Z9 12 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT 15 PY 2005 VL 11 IS 20 BP 7203 EP 7205 DI 10.1158/1078-0432.CCR-05-1845 PG 3 WC Oncology SC Oncology GA 976NB UT WOS:000232739200001 PM 16243788 ER PT J AU Bottaro, DP Linehan, WM AF Bottaro, DP Linehan, WM TI Multifocal renal cancer: Genetic basis and its medical relevance SO CLINICAL CANCER RESEARCH LA English DT Editorial Material ID PARENCHYMAL SPARING SURGERY; HEPATOCYTE GROWTH-FACTOR; CELL CARCINOMA; MET PROTOONCOGENE; INVASIVE GROWTH; CLONAL ORIGIN; TUMOR SIZE; C-MET; METASTASIS; KIDNEY C1 NCI, Ctr Canc Res, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Linehan, WM (reprint author), NCI, Ctr Canc Res, Urol Oncol Branch, NIH, Bldg 10,Room 2B47, Bethesda, MD 20892 USA. EM wml@nih.gov RI Bottaro, Donald/F-8550-2010 OI Bottaro, Donald/0000-0002-5057-5334 NR 23 TC 3 Z9 3 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT 15 PY 2005 VL 11 IS 20 BP 7206 EP 7208 DI 10.1158/1078-0432.CCR-05-1343 PG 3 WC Oncology SC Oncology GA 976NB UT WOS:000232739200002 PM 16243789 ER PT J AU Lepper, ER Baker, SD Permenter, M Ries, N van Schaik, RHN Schenk, PW Price, DK Ahn, D Smith, NF Cusatis, G Ingersoll, RG Bates, SE Mathijssen, RHJ Verweij, J Figg, WD Sparreboom, A AF Lepper, ER Baker, SD Permenter, M Ries, N van Schaik, RHN Schenk, PW Price, DK Ahn, D Smith, NF Cusatis, G Ingersoll, RG Bates, SE Mathijssen, RHJ Verweij, J Figg, WD Sparreboom, A TI Effect of common CYP3A4 and CYP3A5 variants on the pharmacokinetics of the cytochrome P450 3A phenotyping probe midazolam in cancer patients SO CLINICAL CANCER RESEARCH LA English DT Article ID P-GLYCOPROTEIN; GENETIC-VARIABILITY; EUROPEAN-AMERICAN; AFRICAN-AMERICAN; DRUG DISPOSITION; CACO-2 CELLS; IN-VIVO; EXPRESSION; POLYMORPHISM; METABOLISM AB Purpose: To evaluate the effect of naturally occurring variants in genes encoding the cytochrome P450 (CYP) isoforms CYP3A4 and CYP3A5 in patients with cancer receiving midazolam as a phenotyping probe. Experimental Design: Five variants in CYP3A4 and CYP3A5 were evaluated in 58 patients (21 women and 37 men) receiving a short i.v. bolus of midazolam (dose, 0.0145 or 0.025 mg/kg). Midazolam concentrations in plasma were determined using liquid chromatography-mass spectrometry, and pharmacokinetic variables were calculated using noncompartmental analysis. Genomic DNA was characterized for the variants by PCR-RFLP, and all genotypes were confirmed by direct nucleotide sequencing. Results: The mean clearance of midazolam was 24.4 +/- 9.12 L/h, and phenotypic CYP3A activity varied about 4-fold in this population (range, 10.8-44.3 L/h). There were six carriers of the CYP3A4*1B allele (allele frequency, 0.061). No variant alleles for CYP3A4*17, CYP3A4*18A, or CYP3A5*6 were identified. Forty-eight of the 58 patients were homozygous variant for CYP3A5*3C, eight were heterozygous, and two were homozygous wild type (allele frequency, 0.897). No associations were noted between any of the studied genotypes and the phenotypic measures (P >= 0.16). Likewise, a common variant in exon 26 in the gene encoding P-glycoprotein [i.e., ABCB1 (MDR1) 3435C > T] that was previously reported to be linked to CYP3A4 mRNA levels was unrelated to any of the studied phenotypic measures (P >= 0.49). Conclusions. The studied genetic variants in CYP3A4 and CYP3A5 are unlikely to have an important functional significance to phenotypic CYP3A activity in patients with cancer. C1 NCI, Clin Pharmacol Res Core, Bethesda, MD 20892 USA. Sci Applicat Int Corp, Frederick, MD USA. NCI, Mol Pharmacol Sect, Bethesda, MD 20892 USA. NCI, Can Therapeut Branch, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21218 USA. Johns Hopkins Univ, Sch Med, Inst Med Genet, Baltimore, MD 21218 USA. Erasmus Med Ctr, Dept Clin Chem, Rotterdam, Netherlands. Erasmus Med Ctr, Daniel Hoed Canc Ctr, Dept Clin Chem, Rotterdam, Netherlands. RP Sparreboom, A (reprint author), NCI, Clin Pharmacol Res Core, Room 5A01,Bldg 10,9000 Rockville Pike, Bethesda, MD 20892 USA. EM SparrebA@mail.nih.gov RI Sparreboom, Alex/B-3247-2008; Cusatis, Gianluca/G-2539-2011; Figg Sr, William/M-2411-2016 FU NCI NIH HHS [N01-CO-12400] NR 42 TC 49 Z9 53 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT 15 PY 2005 VL 11 IS 20 BP 7398 EP 7404 DI 10.1158/1078-0432.CCR-05-0520 PG 7 WC Oncology SC Oncology GA 976NB UT WOS:000232739200026 PM 16243813 ER PT J AU Cotrim, AP Sowers, AL Lodde, BM Vitolo, JM Kingman, A Russo, A Mitchel, JB Baum, BJ AF Cotrim, AP Sowers, AL Lodde, BM Vitolo, JM Kingman, A Russo, A Mitchel, JB Baum, BJ TI Kinetics of tempol for prevention of xerostomia following head and neck irradiation in a mouse model SO CLINICAL CANCER RESEARCH LA English DT Article ID CANCER CHEMOPREVENTION; ANTIOXIDANT TEMPOL; RADIATION; RADIOTHERAPY; AMIFOSTINE; PROTECTION; THERAPY; DAMAGE AB Purpose: Radiotherapy is commonly used to treat the majority of patients with head and neck cancers. Salivary glands in the radiation field are dramatically affected by this procedure. The purpose of this study was to examine pharmacokinetic characteristics of the stable nitroxide 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (tempol) with respect to radioprotection of the salivary glands. Experimental Design: To evaluate the effect of different doses and times of administration, the heads of C3H mice were exposed to a single irradiation dose of 15 Gy, with i.p. tempol injection. To analyze other routes of administration, we injected 275 mg/kg tempol by an i.m., i.v., or s.c. route, 10 minutes before irradiation. We also tested whether oral administration of tempol in a topical form (either in a mouthwash or gel) provided any salivary gland protection. Results: Tempol treatment (137.5 or 275 mg/kg, i.p., 10 minutes before irradiation) significantly reduced irradiation-induced salivary hypofunction (similar to 50-60%). l.v. or s.c. administration of tempol also showed significant radioprotection, whereas i.m. administration proved to be ineffective. Topical use of tempol, either as a mouthwash or gel, also was radioprotective. Conclusions: Our results strongly suggest that tempol is a promising candidate for clinical application to protect salivary glands in patients undergoing radiotherapy for head and neck cancers. C1 Natl Inst Dent & Craniofacial Res, Gene Therapy & Therapeut Branch, NIH, Bethesda, MD 20892 USA. Natl Inst Dent & Craniofacial Res, Div Clin Res & Hlth Promot, NIH, Bethesda, MD 20892 USA. Natl Canc Inst, Radiat Biol Branch, Ctr Canc Res, Bethesda, MD USA. RP Cotrim, AP (reprint author), Natl Inst Dent & Craniofacial Res, Gene Therapy & Therapeut Branch, NIH, Bldg 10,Room 1N113,MSC-1190, Bethesda, MD 20892 USA. EM acotrim@nidcr.nih.gov NR 26 TC 32 Z9 33 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT 15 PY 2005 VL 11 IS 20 BP 7564 EP 7568 DI 10.1158/1078-0432.CCR-05-0958 PG 5 WC Oncology SC Oncology GA 976NB UT WOS:000232739200045 PM 16243832 ER PT J AU Poola, I Fuqua, SAW De Witty, RL Abraham, J Marshallack, J Liu, AY AF Poola, I Fuqua, SAW De Witty, RL Abraham, J Marshallack, J Liu, AY TI Estrogen receptor alpha-negative breast cancer tissues express significant levels of estrogen-independent transcription factors, ER beta 1 and ER beta 5: Potential molecular targets for chernoprevention SO CLINICAL CANCER RESEARCH LA English DT Article ID RNA COPY NUMBERS; MESSENGER-RNA; ER-BETA; BONE TISSUES; CELL-LINES; PROTEINS; TUMORS; IDENTIFICATION; GLYCOPROTEIN; THERAPY AB We have investigated the expression of two estrogen receptor beta (ER beta) isoforms, ERl3l and ER 5, which activate gene transcription independent of estrogen or growth factors, in ER alpha-negative breast cancer tissues. We report here, for the first time, that ER alpha-negative tissues express significant levels of ER beta 1 and ER beta 5, and their expression levels are not different from levels in ER alpha-positive tumors. However, significant differences exist between the two racial groups, African American and Caucasian, in that the patients from the former group express higher levels of ER beta 1 and ER beta 5 but not ER alpha. These two transcription factors could be potential molecular targets for designing chemopreventive drugs to treat ER alpha-negative breast cancers. C1 Howard Univ, Coll Med, Dept Biochem & Mol Biol, Washington, DC 20059 USA. Howard Univ, Coll Med, Dept Surg Oncol, Washington, DC 20059 USA. Howard Univ, Coll Med, Dept Pathol, Washington, DC 20059 USA. Baylor Coll Med, Breast Ctr, Houston, TX 77030 USA. NICHHD, Biometry & Math Stat Branch, NIH, Bethesda, MD 20892 USA. RP Poola, I (reprint author), Howard Univ, Sch Med, Dept Biochem & Mol Biol, 520 W St NW, Washington, DC 20059 USA. EM ipoola@howard.edu FU NCI NIH HHS [R33 CA88347] NR 30 TC 31 Z9 34 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT 15 PY 2005 VL 11 IS 20 BP 7579 EP 7585 DI 10.1158/1078-0432.CCR-05-0728 PG 7 WC Oncology SC Oncology GA 976NB UT WOS:000232739200047 PM 16243834 ER PT J AU Bisno, AL Rubin, FA Cleary, PP Dale, JB AF Bisno, AL Rubin, FA Cleary, PP Dale, JB TI Prospects for a group a streptococcal vaccine: Rationale, feasibility, and obstacles - Report of a national institute of allergy and infectious diseases workshop SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID GROUP-B STREPTOCOCCI; M-PROTEIN; INTRANASAL IMMUNIZATION; C5A PEPTIDASE; RESPIRATORY-DISEASES; CHALLENGE INFECTIONS; MUCOSAL COLONIZATION; PROTECTIVE IMMUNITY; ENHANCES CLEARANCE; RHEUMATIC-FEVER AB Infections due to group A streptococci (GAS) represent a public health problem of major proportions in both developing and developed countries. Currently available methods of prevention are either inadequate or ineffective, as attested to by the morbidity and mortality associated with this ubiquitous pathogen worldwide. Advances in molecular biology have shed new light on the pathogenesis of GAS infections and have identified a number of virulence factors as potential vaccine targets. Therefore, the National Institute of Allergy and Infectious Diseases convened an expert workshop in March 2004 to review the available data and to explore the microbiologic, immunologic, epidemiologic, and economic issues involved in development and implementation of a safe and effective GAS vaccine. Participants included scientists and clinicians involved in GAS research, as well as representatives of United States federal agencies (Centers for Disease Control and Prevention, Food and Drug Administration, Department of Defense, and National Institute of Allergy and Infectious Diseases), the World Health Organization, and the pharmaceutical industry. This report summarizes the deliberations of the workshop. C1 Miami VA Med Ctr, Miami, FL 33125 USA. Univ Miami, Miller Sch Med, Miami, FL 33152 USA. NIAID, NIH, Bethesda, MD 20892 USA. Univ Minnesota, Minneapolis, MN USA. Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA. Vet Affairs Med Ctr, Memphis, TN USA. RP Bisno, AL (reprint author), Miami VA Med Ctr, 1201 NW 16th St, Miami, FL 33125 USA. EM abisno@med.miami.edu FU NIAID NIH HHS [R37AI-10085, R01AI-200016, U01AI-60592] NR 54 TC 62 Z9 65 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD OCT 15 PY 2005 VL 41 IS 8 BP 1150 EP 1156 DI 10.1086/444505 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 966EJ UT WOS:000232002300012 PM 16163634 ER PT J AU Nakai, K Mason, RP AF Nakai, K Mason, RP TI Immunochemical detection of nitric oxide and nitrogen dioxide trapping of the tyrosyl radical and the resulting nitrotyrosine in sperm whale myoglobin SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE sperm whale myoglobin; tyrosyl radical; nitric oxide; nitrogen dioxide; 5,5-dimethyl-1-pyrroline N-oxide; nitrotyrosine; immuno-spin trapping; free radicals ID HYDROGEN-PEROXIDE; RIBONUCLEOTIDE REDUCTASE; CYTOCHROME-C; HORSERADISH-PEROXIDASE; SUPEROXIDE-DISMUTASE; ESCHERICHIA-COLI; PHOTOSYSTEM-II; PEROXYNITRITE; OXIDATION; NITRATION AB We demonstrate herein that nitric oxide ((NO)-N-center dot) and nitrogen dioxide ((NO2)-N-center dot) both react with the tyrosyl radical formed in sperm whale myoglobin (swMb) by reaction with hydrogen peroxide. The tyrosyl radical was detected by Western blotting using a novel anti-5,5-dimethyl-1-pyrroline N-oxide (DMPO) polyclonal antiserum that specifically recognizes protein radical-derived DMPO nitrone adducts. In the presence of DMPO, hydrogen peroxide reacts with swMb to form the DMPO tyrosyl radical as is known from both electron spin resonance and immuno-spin trapping investigations. Both (NO)-N-center dot and (NO2-)-N-center dot significantly suppressed DMPO-Mb formation under the physiological oxygen tension of 30 mm Hg. If this inhibition of DMPO trapping of the tyrosyl radical is due, at least in part, to the reaction of the tyrosyl radical with (NO)-N-center dot and (NO2)-N-center dot, then nitrotyrosine should be formed. In line with this expectation, swMb treated with low concentrations of (NO)-N-center dot or (NO2-)-N-center dot formed nitrotyrosine when hydrogen peroxide was added under 30 min Hg oxygen tension as detected by Western blotting. The amount of nitrotyrosine generated with (NO)-N-center dot was higher than with NO2-, implying that there are two different peroxynitrite-independent nitrotyrosine formation mechanisms and that (NO)-N-center dot is not just a source of (NO2)-N-center dot. Published by Elsevier B.V. C1 NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. RP Nakai, K (reprint author), NIEHS, Lab Pharmacol & Chem, NIH, POB 12233,MD F0-01, Res Triangle Pk, NC 27709 USA. EM nakai@niehs.nih.gov NR 53 TC 19 Z9 19 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD OCT 15 PY 2005 VL 39 IS 8 BP 1050 EP 1058 DI 10.1016/j.freeradbiomed.2005.05.019 PG 9 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 975PF UT WOS:000232673700008 PM 16198232 ER PT J AU Brown, TA Cecconi, C Tkachuk, AN Bustamante, C Clayton, DA AF Brown, TA Cecconi, C Tkachuk, AN Bustamante, C Clayton, DA TI Replication of mitochondrial DNA occurs by strand displacement with alternative light-strand origins, not via a strand-coupled mechanism SO GENES & DEVELOPMENT LA English DT Article DE replication; mtDNA; branch migration; atomic force microscopy; 2D agarose gels; strand displacement ID MOUSE L-CELLS; CLOSED CIRCULAR TEMPLATE; 5' ENDS; MOLECULES; GENOME; RNA; COMPLEXES; SEQUENCE; BUBBLE; BURST AB The established strand-displacement model for mammalian mitochondrial DNA (mtDNA) replication has recently been questioned in light of new data using two-dimensional (2D) agarose gel electrophoresis. It has been proposed that a synchronous, strand-coupled mode of replication occurs in tissues, thereby casting doubt on the general validity of the "orthodox," or strand-displacement model. We have examined mtDNA replicative intermediates from mouse liver using atomic force microscopy and 2D agarose gel electrophoresis in order to resolve this issue. The data provide evidence for only the orthodox, strand-displacement mode of replication and reveal the presence of additional, alternative origins of lagging light-strand mtDNA synthesis. The conditions used for 2D agarose gel analysis are favorable for branch migration of asymmetrically replicating nascent strands. These data reconcile the original displacement mode of replication with the data obtained from 2D gel analyses. C1 Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. NINDS, NIH, Bethesda, MD 20892 USA. Lawrence Berkeley Natl Lab, Berkeley, CA 94720 USA. Univ Calif Berkeley, Howard Hughes Med Inst, Dept Mol & Cell Biol, Berkeley, CA 94720 USA. Univ Calif Berkeley, Dept Phys, Berkeley, CA 94720 USA. RP Clayton, DA (reprint author), Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. EM brownt@hhmi.org; clayton@hhmi.org RI Cecconi, Ciro/K-5028-2016 OI Cecconi, Ciro/0000-0002-6101-2609 NR 41 TC 103 Z9 103 U1 1 U2 3 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD OCT 15 PY 2005 VL 19 IS 20 BP 2466 EP 2476 DI 10.1101/gad.1352105 PG 11 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 975PV UT WOS:000232675300009 PM 16230534 ER PT J AU Strizzi, L Bianco, C Raafat, A Abdallah, W Chang, C Raafat, D Hirota, M Hamada, S Sun, YP Normanno, N Callahan, R Hinck, L Saloman, D AF Strizzi, L Bianco, C Raafat, A Abdallah, W Chang, C Raafat, D Hirota, M Hamada, S Sun, YP Normanno, N Callahan, R Hinck, L Saloman, D TI Netrin-1 regulates invasion and migration of mouse mammary epithelial cells overexpressing Cripto-1 in vitro and in vivo SO JOURNAL OF CELL SCIENCE LA English DT Article DE mammary cells; Netrin-1; Cripto-1; invasion; migration ID CERVICAL-CARCINOMA CELLS; COLORECTAL-CANCER DCC; GROWTH-FACTOR-ALPHA; MESENCHYMAL TRANSITIONS; BREAST-CANCER; AXON GUIDANCE; E-CADHERIN; BRANCHING MORPHOGENESIS; VIMENTIN EXPRESSION; COMMISSURAL AXONS AB The neuronal guidance molecule, Netrin-1, has been suggested to play a role in the adhesion and migration of the mammary gland epithelium. Human and mouse Cripto-1 induce proliferation, migration, invasion and colony formation by epithelial cells in 3D matrices. Here we investigate whether Netrin-1 affects these Cripto-1-dependent activities in mouse mammary epithelial cells. Overexpression of Cripto-1 in EpH4 and HC-11 cells (EpH4/Cripto-1 or HC-11/Cripto-1) was associated with low expression of Netrin-1 and increased expression of its receptor Neogenin compared to that of wild-type cells. No change was observed in the expression of the other Netrin-1 receptor, UNC5H1. Treating EpH4/Cripto-1 or HC-11/Cripto-1 mammary cells with exogenous soluble Netrin-1 resulted in increased expression of E-cadherin and UNC5H1, decreased expression of vimentin and decreased activation of Akt as determined by western blotting. Colony formation by Eph4/Cripto-1 cells in 3D gels was significantly reduced in proximity to a Netrin-1 source, and mammary glands of transgenic mice overexpressing human Cripto-1 showed altered ductal growth in proximity to implanted Netrin-l-releasing pellets. Terminal end buds in the treated transgenic mice mammary glands also showed increased expression of E-cadherin and UNC5H1 and decreased expression of active Akt determined by immunohistochemistry. Together, these results suggest that regulation of Netrin-1 expression is important in regulating Cripto-l-dependent invasion and migration of mammary epithelial cells. C1 NCI, CCR, Mammary Biol & Tumorigenesis Lab, Bethesda, MD 20892 USA. INT, Fdn Pascale, Cell Biol & Preclin Models Unit, I-80131 Naples, Italy. Univ Calif Santa Cruz, Dept Biol, Santa Cruz, CA 95064 USA. RP Saloman, D (reprint author), NCI, CCR, Mammary Biol & Tumorigenesis Lab, 37 Convent Dr,Bldg 37, Bethesda, MD 20892 USA. EM salomond@mail.nih.gov OI Hinck, Lindsay/0000-0002-4009-3913; Normanno, Nicola/0000-0002-7158-2605 NR 73 TC 26 Z9 26 U1 0 U2 3 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD OCT 15 PY 2005 VL 118 IS 20 BP 4633 EP 4643 DI 10.1242/jcs.02574 PG 11 WC Cell Biology SC Cell Biology GA 985QF UT WOS:000233392300005 PM 16176936 ER PT J AU Varnai, P Bondeva, T Tamas, P Toth, B Buday, L Hunyady, L Balla, T AF Varnai, P Bondeva, T Tamas, P Toth, B Buday, L Hunyady, L Balla, T TI Selective cellular effects of overexpressed pleckstrin-homology domains that recognize PtdIns(3,4,5)P-3 suggest their interaction with protein binding partners SO JOURNAL OF CELL SCIENCE LA English DT Article DE PH domain; PI 3-kinase; PtdIns(3,4,5)P-3; PIP3; Akt kinase; cell adhesion; GFP ID GUANINE-NUCLEOTIDE EXCHANGE; G-BETA-GAMMA; BRUTON TYROSINE KINASE; PHOSPHOLIPASE C-GAMMA; PH DOMAIN; PHOSPHATIDYLINOSITOL 3,4,5-TRISPHOSPHATE; CRYSTAL-STRUCTURE; INOSITOL LIPIDS; LIVING CELLS; MEMBRANE AB Several pleckstrin-homology (PH) domains with the ability to bind phosphatidylinositol (3,4,5)-trisphosphate [PtdIns(3,4,5)P-3, PIP3] were expressed as green fluorescent protein (GFP) fusion proteins to determine their effects on various cellular responses known to be activated by PIP3. These proteins comprised the PH domains of Akt, ARNO, Btk or GRP1, and were found to show growth-factor-stimulated and wortmannin-sensitive translocation from the cytosol to the plasma membrane in several cell types, indicating their ability to recognize PIP3. Remarkably, although overexpressed Akt-PH-GFP and Btk-PH-GFP were quite potent in antagonizing the PIP3-mediated activation of the Akt protein kinase, such inhibition was not observed with the other PH domains. By contrast, expression of the PH domains of GRP1 and ARNO, but not of Akt or Btk, inhibited the attachment and spreading of freshly seeded cells to culture dishes. Activation of PLC gamma by epidermal growth factor (EGF) was attenuated by the PH domains of GRP1, ARNO and Akt, but was significantly enhanced by the Btk PH domain. By following the kinetics of expression of the various GFP-fused PH domains for several days, only the PH domain of Akt showed a lipid-binding-dependent self-elimination, consistent with its interference with the anti-apoptotic Akt signaling pathway. Mutations of selective residues that do not directly participate in PIP3 binding in the GRP1-PH and Akt-PH domain were able to reduce the dominant-negative effects of these constructs yet retain their lipid binding. These data suggest that interaction with and sequestration Of PIP3 may not be the sole mechanism by which PH domains interfere with cellular responses and that their interaction with other membrane components, most probably with proteins, allows a more specific participation in the regulation of specific signaling pathways. C1 Natl Inst Child Hlth & Human Dev, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. Semmelweis Univ, Fac Med, Dept Physiol, H-1085 Budapest, Hungary. Semmelweis Univ, Fac Med, Dept Med Chem, H-1085 Budapest, Hungary. RP Balla, T (reprint author), Natl Inst Child Hlth & Human Dev, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. EM ballat@mail.nih.gov RI Toth, Balazs/B-4252-2012 FU Intramural NIH HHS; Wellcome Trust NR 48 TC 86 Z9 89 U1 0 U2 9 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD OCT 15 PY 2005 VL 118 IS 20 BP 4879 EP 4888 DI 10.1242/jcs.02606 PG 10 WC Cell Biology SC Cell Biology GA 985QF UT WOS:000233392300025 PM 16219693 ER PT J AU Norman, AI Ivkov, R Forbes, JG Greer, SC AF Norman, AI Ivkov, R Forbes, JG Greer, SC TI The polymerization of actin: Structural changes from small-angle neutron scattering SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID INDIRECT FOURIER TRANSFORMATION; DYNAMIC LIGHT-SCATTERING; X-RAY-DIFFRACTION; CELL BIOLOGY; INTERACTING PARTICLES; F-ACTIN; WATER; FILAMENT; DIMERS; MECHANISM AB We present a new analysis of small- angle neutron- scattering data from rabbit muscle actin in the course of the polymerization from G- actin to F- actin as a function of temperature. The data, from Ivkov et al. [J. Chem. Phys. 108, 5599 (1998)], were taken in D2O buffer with Ca2+ as the divalent cation on the G- actin in the presence of ATP and with KCl as the initiating salt. The new analysis of the data using modeling and the method of generalized indirect fourier transform (O. Glatter, GIFT, University of Graz, Austria, http://physchem.kfunigraz.ac.at/sm/) provide shapes and dimensions of the G- actin monomer and of the growing actin oligomer in solution as a function of temperature and salt concentration. This analysis indicates that the G-actin monomer, under the conditions given above, is a sphere 50 - 54 angstrom in diameter as opposed to the oblate ellipsoid seen by x-ray crystallography. The F-actin dimensions are consistent with x- ray crystal structure determinations. (c) 2005 American Institute of Physics. C1 Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA. Univ Maryland, Dept Chem & Biomol Engn, College Pk, MD 20742 USA. Triton BioSyst Inc, Chelmsford, MA 01824 USA. NIAMS, Proteom & Nanotechnol Sect, Muscle Biol Lab, DHHS,NIH, Bethesda, MD 20892 USA. RP Norman, AI (reprint author), Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA. EM anorman1@umd.edu; sgreer@umd.edu RI Ivkov, Robert/A-3902-2015 OI Ivkov, Robert/0000-0002-2930-5276 NR 60 TC 10 Z9 10 U1 0 U2 2 PU AMER INST PHYSICS PI MELVILLE PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1, MELVILLE, NY 11747-4501 USA SN 0021-9606 J9 J CHEM PHYS JI J. Chem. Phys. PD OCT 15 PY 2005 VL 123 IS 15 AR 154904 DI 10.1063/1.2039088 PG 11 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 975XR UT WOS:000232697900036 PM 16252969 ER PT J AU Woszczek, G Pawliczak, R Qi, HY Nagineni, S Alsaaty, S Logun, C Shelhamer, JH AF Woszczek, G Pawliczak, R Qi, HY Nagineni, S Alsaaty, S Logun, C Shelhamer, JH TI Functional characterization of human cysteinyl leukotriene 1 receptor gene structure SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; HUMAN MAST-CELLS; 5-LIPOXYGENASE PATHWAY; ALLERGIC INFLAMMATION; MOLECULAR-CLONING; ASTHMATIC AIRWAYS; DEFICIENT MICE; EXPRESSION; CYTOKINE; STAT6 AB The 5-lipoxygenase pathway has been strongly implicated in the pathogenesis of chronic inflammatory disorders, such as bronchial asthma and atherosclerosis. Cysteinyl leukotrienes (cysLTs), 5-lipoxygenase pathway products, are recognized now not only as important factors in asthmatic inflammation, but also as mediators of cell trafficking and innate immune responses. To study a role of cysLTs in inflammatory reactions we have characterized the gene structure of human cysteinyl leukotriene receptor type I (cysLT(1)R). The cysLT(1)R gene consists of 5 exons that are variably spliced and a single promoter region with multiple transcription start sites. Four different cysLT(1)R transcripts were identified. RT-PCR showed dominant and wide expression of the transcript 1, containing exons 1, 4, and 5, with the strongest presence in blood leukocytes, spleen, thymus, lung, and heart. The expression of cysLT(1)R is functionally regulated at the transcriptional level by IL-4 through a STAT6 response element localized to the proximal cysLT(1)R promoter region. IL-4 stimulation increased cysLT(1)R mRNA (real-time PCR) and surface protein expression (flow cytometry) in a time-dependent fashion. CysLTs (LTD4 and LTC4) induced an increased production of a potent monocyte chemoattractant CCL2 (MCP-1) in IL-4-primed THP-1 cells in a dose-dependent manner. This effect was effectively inhibited by the cysLT(1)R-selective antagonist MK571 in a dose-dependent manner and only partially by a nonselective cysLT(1)R/cysLT(2)R inhibitor BAY-u9773, implying a cysLT(1)R-mediated mechanism. Thus, cysLTs signaling through cysLT(1)R might contribute to inflammatory reactions by cooperating with IL-4 in enhanced CCL2 production in human monocytic cells. C1 NIH, Warren Grant Magnuson Clin Ctr, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. Med Univ Lodz, Dept Immunopathol, Lodz, Poland. RP Shelhamer, JH (reprint author), NIH, Warren Grant Magnuson Clin Ctr, Dept Crit Care Med, Ctr Clin, Bldg 10,Room 7D43,9000 Rockville Pike, Bethesda, MD 20892 USA. EM jshelhamer@cc.nih.gov RI Woszczek, Grzegorz/H-5792-2012; Pawliczak, Rafal/S-9649-2016 NR 43 TC 37 Z9 39 U1 0 U2 5 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 15 PY 2005 VL 175 IS 8 BP 5152 EP 5159 PG 8 WC Immunology SC Immunology GA 972GY UT WOS:000232443500038 PM 16210619 ER PT J AU Bonniaud, P Margetts, PJ Ask, K Flanders, K Gauldie, J Kolb, M AF Bonniaud, P Margetts, PJ Ask, K Flanders, K Gauldie, J Kolb, M TI TGF-beta and Smad3 signaling link inflammation to chronic fibrogenesis SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IDIOPATHIC PULMONARY FIBROSIS; GROWTH-FACTOR-BETA; LUNG FIBROSIS; TRANSFORMING GROWTH-FACTOR-BETA-1; TISSUE FIBROSIS; MINOR COMPONENT; RAT LUNG; BLEOMYCIN; MICE; PATHOGENESIS AB Transient adenovirus-mediated gene transfer of IL-1 beta (AdIL-1 beta), a proinflammatory cytokine, induces marked inflammation and severe and progressive fibrosis in rat lungs. This is associated with an increase in TGF-beta 1 concentration in bronchoalveolar lavage (BAL) fluid. TGF-beta 1 is a key cytokine in the process of fibrogenesis, using intracellular signaling pathways involving Smad2 and Smad3. In this study we investigate whether inflammation induced by IL-1 beta is able to independently induce lung fibrosis in mice deficient in the Smad3 gene. Seven days after AdIL-1 beta administration, similar levels of IL-1 beta transgene are seen in BAL in both wild-type (WT) and knockout (KO) mice, and BAL cell profiles demonstrated a similar marked neutrophilic inflammation. Phospho-Smad2 staining was positive in areas of inflammation in both WT and KO mice at day 7. By day 35 after transient IL-1 beta expression, WT mice showed marked fibrosis in peribronchial areas, quantified by picrosirius red staining and morphometry. However, there was no evidence of fibrosis or collagen accumulation in IL-1 beta-treated KO mice, and peribronchial areas were not different from KO mice treated with the control adenovector. TGF-beta 1 and phospho-Smad2 were strongly positive at day 35 in fibrotic areas observed in WT mice, but no such staining was detectable in KO mice. The IL-1 beta-induced chronic fibrotic response in mouse lungs is dependent on Smad3. KO and WT animals demonstrated a similar inflammatory response to overexpression of IL-1 beta indicating that inflammation must link to the Smad3 pathway, likely through TGF-beta, to induce progressive fibrosis. C1 McMaster Univ, Dept Pathol & Mol Med, Ctr Gene Therapeut, Hamilton, ON L8N 4A6, Canada. Ctr Hosp Univ Bocage, Serv Pneumol & Reanimat Resp, Dijon, France. Univ Bourgogne, Dijon, France. NCI, NIH, Bethesda, MD 20892 USA. McMaster Univ, Firestone Inst Resp Hlth, Dept Med, Hamilton, ON L8N 4A6, Canada. RP Kolb, M (reprint author), McMaster Univ, Firestone Inst Resp Hlth, Dept Med, 50 Charlton Ave E,Room T2121, Hamilton, ON L8N 4A6, Canada. EM kolbm@mcmaster.ca RI Ask, Kjetil/B-6833-2015 OI Ask, Kjetil/0000-0002-0202-735X NR 30 TC 146 Z9 164 U1 1 U2 9 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 15 PY 2005 VL 175 IS 8 BP 5390 EP 5395 PG 6 WC Immunology SC Immunology GA 972GY UT WOS:000232443500064 PM 16210645 ER PT J AU Lu, YB Wahl, LM AF Lu, YB Wahl, LM TI Oxidative stress augments the production of matrix metalloproteinase-1, cyclooxygenase-2, and prostaglandin E2 through enhancement of NF-kappa B activity in lipopolysaccharide-activated human primary monocytes SO JOURNAL OF IMMUNOLOGY LA English DT Article ID EPIDERMAL-GROWTH-FACTOR; TUMOR-NECROSIS-FACTOR; HYDROGEN-PEROXIDE; FREE-RADICALS; TYROSINE PHOSPHORYLATION; ATHEROSCLEROTIC LESIONS; ANTIINFLAMMATORY DRUGS; TRANSCRIPTION FACTORS; HUMAN NEUTROPHILS; HUMAN MACROPHAGES AB The excessive production of reactive oxidative species (ROS) associated with inflammation leads to a condition of oxidative stress. Cyclooxygenase-2 (COX-2), PGE(2), and matrix metalloproteinases (MMPs) are important mediators during the process of inflammation. In this paper we report on studies examining how the ROS hydrogen peroxide (H2O2) affects the production of MMP-1, COX-2, and PGE(2). Addition of H2O2 to LPS-activated monocytes, but not naive monocytes, caused a significant enhancement of the LPS-induced production of MMP-1, COX-2, and PGE(2). The mechanism by which H2O2 increased these mediators was through enhancement of I kappa B alpha degradation, with subsequent increases in NF-kappa B activation and NF-kappa B. p50 translocation to the nucleus. The effects of H2O2 on I kappa B alpha degradation, NF-kappa B activation, and NF-kappa B p50 localization to the nucleus were demonstrated through studies of coimmunoprecipitation of I kappa B alpha with p50, ELISA of NF-kappa B p65 activity, and Western blot analysis of the nuclear fraction extract for p50. The key role for NF-kappa B in this process was demonstrated by the ability of MG-132 or lactacystin (proteasome inhibitors) to block the enhanced production of MMP-1, COX-2, and PGE(2). In contrast, indomethacin, which inhibited PGE(2) production, partially blocked the enhanced MMP-1 production. Moreover, although PGE(2) restored MMP-1 production in indomethacin-treated monocyte cultures; it failed to significantly restore MMP-1 production in proteasome inhibitor-treated cultures. Thus, in the presence of LPS and H2O2, NF-kappa B plays a dominate role in the regulation of MMP-1, COX-2, and PGE(2) expression. C1 Natl Inst Dent & Craniofacial Res, Immunopathol Sect, NIH, Bethesda, MD 20892 USA. RP Wahl, LM (reprint author), Natl Inst Dent & Craniofacial Res, Immunopathol Sect, NIH, Bldg 30,Room 3A300,30 Convent Dr, Bethesda, MD 20892 USA. EM lwahl@dir.nidcr.nih.gov FU Intramural NIH HHS NR 50 TC 105 Z9 115 U1 1 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 15 PY 2005 VL 175 IS 8 BP 5423 EP 5429 PG 7 WC Immunology SC Immunology GA 972GY UT WOS:000232443500068 PM 16210649 ER PT J AU Pasquetto, V Bui, HH Giannino, R Mirza, F Sidney, J Oseroff, C Tscharke, DC Irvine, K Bennink, JR Peters, B Southwood, S Cerundolo, V Grey, H Yewdell, JW Sette, A AF Pasquetto, V Bui, HH Giannino, R Mirza, F Sidney, J Oseroff, C Tscharke, DC Irvine, K Bennink, JR Peters, B Southwood, S Cerundolo, V Grey, H Yewdell, JW Sette, A TI HLA-A*0201, HLA-A*1101, and HLA-B*0702 transgenic mice recognize numerous poxvirus determinants from a wide variety of viral gene products SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; T-CELL EPITOPES; FUNCTIONAL CTL REPERTOIRE; INFLUENZA-A VIRUSES; CLASS-I MOLECULES; SMALLPOX VACCINATION; ANTIGENIC PEPTIDES; DISULFIDE BONDS; MURINE CELLS; HLA-A AB In virus models explored in detail in mice, CTL typically focus on a few immunodominant determinants. In this study we use a multipronged approach to understand the diversity of CTL responses to vaccinia virus, a prototypic poxvirus with a genome similar to 20-fold larger than that of the model RNA viruses typically studied in mice. Based on predictive computational algorithms for peptide binding to HLA supertypes, we synthesized a panel of 2889 peptides to begin to create an immunomic map of human CTL responses to poxviruses. Using this panel in conjunction with CTLs from vaccinia virus-infected HLA transgenic mice, we identified 14 HLA-A*0201-, 4 HLA-A*1101-, and 3 HLA-B*0702-restricted CD8(+) T cell determinants distributed over 20 distinct proteins. These peptides were capable of binding one or multiple A2, A3, and B7 supertype molecules with affinities typical of viral determinants. Surprisingly, many of the viral proteins recognized are predicted to be late gene products, in addition to the early intermediate gene products expected. Nearly all of the determinants identified have identical counterparts encoded by modified vaccinia virus Ankara as well as variola virus, the agent of smallpox. These findings have implications for the design of new smallpox vaccines and the understanding of immune responses to large DNA viruses in general. C1 La Jolla Inst Allergy & Immunol, San Diego, CA 92109 USA. Univ Oxford, Weatherall Inst Mol Med, Tumor Immunol Unit, Oxford, England. Epimmune Inc, San Diego, CA 92121 USA. NIH, Viral Dis Lab, Bethesda, MD 20892 USA. Queensland Inst Med Res, Div Infect Dis & Immunol, Herston, Qld 4006, Australia. RP Sette, A (reprint author), La Jolla Inst Allergy & Immunol, 3030 Bunker Hill St,Suite 326, San Diego, CA 92109 USA. EM alex@liai.org RI yewdell, jyewdell@nih.gov/A-1702-2012; Tscharke, David/C-9133-2009; OI Tscharke, David/0000-0001-6825-9172; Cerundolo, Vincenzo/0000-0003-0040-3793 FU NIAID NIH HHS [R01AI56268] NR 45 TC 68 Z9 68 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 15 PY 2005 VL 175 IS 8 BP 5504 EP 5515 PG 12 WC Immunology SC Immunology GA 972GY UT WOS:000232443500078 PM 16210659 ER PT J AU Wawer, MJ Serwadda, D Quinn, TC Sewankambo, N Kiwanuka, N Li, XB Gray, RH AF Wawer, MJ Serwadda, D Quinn, TC Sewankambo, N Kiwanuka, N Li, XB Gray, RH TI Questioning Wawer et al.'s estimated rate of sexual HIV transmission from persons with early HIV infections - Reply to Gisselquist and Potterat SO JOURNAL OF INFECTIOUS DISEASES LA English DT Letter ID RURAL UGANDA; COUPLES; DISCORDANT; COHORT; RAKAI; MEN C1 Columbia Univ, Sch Publ Hlth, New York, NY 10027 USA. Johns Hopkins Med Inst, Baltimore, MD 21205 USA. John Hopkins Bloomberg, Sch Publ Hlth, Baltimore, MD USA. NIAID, Bethesda, MD 20892 USA. Makerere Univ, Inst Publ Hlth, Kampala, Uganda. Makerere Univ, Fac Med, Kampala, Uganda. Rakai Hlth Sci Program, Kalisizo, Rakai, Uganda. RP Wawer, MJ (reprint author), Columbia Univ, Sch Publ Hlth, New York, NY 10027 USA. EM mwawer@jhsph.edu NR 12 TC 1 Z9 1 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD OCT 15 PY 2005 VL 192 IS 8 BP 1499 EP 1500 DI 10.1086/462432 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 966EI UT WOS:000232002200030 ER PT J AU Mitz, AR AF Mitz, AR TI A liquid-delivery device that provides precise reward control for neurophysiological and behavioral experiments SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE fluid dispenser; behavioral neurophysiology; automated reinforcement; reward delivery ID CORTEX AB Behavioral neurophysiology and other kinds of behavioral research often involve the delivery of liquid rewards to experimental subjects performing some kind of operant task. Available systems use gravity or pumps to deliver these fluids, but such methods are poorly suited to moment-to-moment control of the volume, timing, and type of fluid delivered. The design described here overcomes these limitations using an electronic control unit, a pressurized reservoir unit, and an electronically controlled solenoid. The control unit monitors reservoir pressure and provides precisely timed solenoid activation signals. It also stores calibration tables and does on-the-fly interpolation to support computer-controlled delivery calibrated directly in milliliters. The reservoir provides pressurized liquid to a solenoid mounted near the subject. Multiple solenoids, each supplied by a separate reservoir unit and control unit, can be stacked in close proximity to allow instantaneous selection of which liquid reward is delivered. The precision of droplet delivery was verified by weighing discharged droplets on a commercial analytical balance. Published by Elsevier B.V. C1 NIMH, Lab Syst Neurosci, Bethesda, MD 20892 USA. RP Mitz, AR (reprint author), NIMH, Lab Syst Neurosci, 49 Convent Dr MSC 4401, Bethesda, MD 20892 USA. EM arm@nih.gov FU Intramural NIH HHS NR 5 TC 12 Z9 12 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 J9 J NEUROSCI METH JI J. Neurosci. Methods PD OCT 15 PY 2005 VL 148 IS 1 BP 19 EP 25 DI 10.1016/j.jneumeth.2005.07.012 PG 7 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 978LH UT WOS:000232874300002 PM 16168492 ER PT J AU Hu, XQ Lovinger, DM AF Hu, XQ Lovinger, DM TI Role of aspartate 298 in mouse 5-HT3A receptor gating and modulation by extracellular Ca2+ SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID GATED ION-CHANNEL; NEURONAL NICOTINIC RECEPTORS; GLYCINE RECEPTOR; AGONIST BINDING; M2-M3 LOOP; AMINO-ACID; HIPPOCAMPAL INTERNEURONS; GABA(A) RECEPTOR; OPEN STATE; ACETYLCHOLINE AB The TM2-TM3 extracellular loop is critical for activation of the Cys-loop family of ligand-gated ion channels. The contribution of aspartate 298 (D298), an amino acid that links the transmembrane domain 2 (TM2) to the TM2-TM3 loop, in mouse 5-hydroxytryptamine(3A) (5-HT3A) receptor function was probed with site-directed mutagenesis in the present study. This negatively charged residue was replaced with an alanine to neutralize the charge, with a glutamate to conserve the charge, or with an arginine to reverse the charge. Human embryonic kidney 293 (HEK 293) cells transfected with the wild-type and mutant receptors were studied by combining whole-cell patch-clamp recording with fast agonist application. The D -> A or D -> R mutations resulted in a receptor with reduced 5-HT potency, and accelerated kinetics of desensitization and deactivation. In addition, the efficacy of partial agonists was reduced by the D -> A mutation. The D -> E mutation produced a receptor with properties similar to those of the wild-type receptor. In addition, the potential role of this residue in modulation of the receptor by extracellular calcium ([Ca2+](o)) was investigated. Increasing [Ca2+]. inhibited 5-HT-activated currents and altered receptor kinetics in a similar manner in the wild-type and D298E receptors, and this alteration was eliminated by the D -> A and D -> R mutations. Our data suggest that the charge at D298 participates in transitions between functional states of the 5-HT3A receptor, and provide evidence that the charge of the side-chain at residue D298 contributes to channel gating kinetics and is crucial for Ca2+ modulation. C1 NIAAA, Lab Integrat Neurosci, NIH, Bethesda, MD 20892 USA. RP Lovinger, DM (reprint author), NIAAA, Lab Integrat Neurosci, NIH, 5625 Fishers Lane,Room TS 13A, Bethesda, MD 20892 USA. EM lovindav@mail.nih.gov NR 53 TC 17 Z9 17 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD OCT 15 PY 2005 VL 568 IS 2 BP 381 EP 396 DI 10.1113/jphysiol.2005.092866 PG 16 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 977ZU UT WOS:000232842800004 PM 16096341 ER PT J AU Ghanayem, BI Witt, KL Kissling, GE Tice, RR Recio, L AF Ghanayem, BI Witt, KL Kissling, GE Tice, RR Recio, L TI Absence of acrylamide-induced genotoxicity in CYP2E1-null mice: Evidence consistent with a glycidamide-mediated effect SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE acrylamide; glycidamide; micronuclei; DNA damage; comet assay; genotoxicity; CYP2E1-null mice ID WILD-TYPE MICE; CYTOCHROME-P450 2E1 CYP2E1; HUMAN PERIPHERAL-BLOOD; MOUSE GERM-CELLS; HERITABLE TRANSLOCATIONS; HEMOGLOBIN ADDUCTS; MICRONUCLEATED RETICULOCYTES; LOCUS MUTATIONS; C-14 ACRYLAMIDE; FLOW CYTOMETER AB Acrylamide, an animal carcinogen and germ cell mutagen present at low (ppm) levels in heated carbohydrate-containing foodstuffs, is oxidized by cytochrome P4502E1 (CYP2E1) to the epoxide glycidamide, which is believed to be responsible for the mutagenic and carcinogenic activity of acrylamide. We recently reported a comparison of the effects of acrylamide on the genetic integrity of germ cells of male wild-type and CYP2E1-null mice [B.I. Ghanayem, K.L. Witt, L. El-Hadri, U. Hoffler, G.E. Kissling, M.D. Shelby, J.B. Bishop, Comparison of germ-cell mutagenicity in male CYP2E1-nulI and wild-type mice treated with acrylamide: evidence supporting a glycidamide-mediated effect, Biol. Reprod. 72 (2005) 157-163]. In those experiments, dose-related increases in dominant lethal mutations were detected in uterine contents of female mice mated to acrylamide-treated wild-type males but not CYP2E1-null males, clearly implicating CYP2E1-mediated formation of glycidamide in the induction of genetic damage in male germ cells. We hypothesized that acrylamide-induced somatic cell damage is also caused by glycidamide. Therefore, to examine this hypothesis, female wild-type and CYP2E1-null mice were administered acrylamide (0, 25, 50 mg/kg) by intraperitoneal injection once daily for 5 consecutive days. Twenty-four hours after the final treatment, blood and tissue samples were collected. Erythrocyte micronucleus frequencies were determined using flow cytometry and DNA damage was assessed in leukocytes, liver, and lung using the alkaline (pH > 13) single cell gel electrophoresis (Comet) assay. Results were consistent with the earlier observations in male germ cells: significant dose-related increases in micronucleated erythrocytes and DNA damage in somatic cells were induced in acrylamide-treated wild-type but not in the CYP2E1-null mice. These results support the hypothesis that genetic damage in somatic and germ cells of mice-treated with acrylamide is dependent upon metabolism of the parent compound by CYP2E1. This dependency on metabolism has implications for the assessment of human risks resulting from occupational or dietary exposure to acrylamide. CYP2E1 polymorphisms and variability in CYP2E1 activity associated with, for example, diabetes, obesity, starvation, and alcohol consumption. may result in altered metabolic efficiencies leading to differential susceptibilities to acrylamide toxicities in humans. Published by Elsevier B.V. C1 NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Environm Toxicol Program, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Biostat Branch, NIH, Res Triangle Pk, NC 27709 USA. ILS Inc, Res Triangle Pk, NC 27709 USA. RP Ghanayem, BI (reprint author), NIEHS, Lab Pharmacol & Chem, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM ghanayem@niehs.nih.gov NR 47 TC 74 Z9 77 U1 0 U2 16 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD OCT 15 PY 2005 VL 578 IS 1-2 BP 284 EP 297 DI 10.1016/j.mrfmmm.2005.05.004 PG 14 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 976QF UT WOS:000232747600027 PM 15982677 ER PT J AU Simmons, A Miller, D Feinstein, JS Goldberg, TE Paulus, MP AF Simmons, A Miller, D Feinstein, JS Goldberg, TE Paulus, MP TI Left inferior prefrontal cortex activation during a semantic decision-making task predicts the degree of semantic organization SO NEUROIMAGE LA English DT Article DE decision-making task; semantic organization; IPFC ID ALZHEIMERS-DISEASE; RETRIEVAL; KNOWLEDGE AB Semantic organization, an aspect of semantic processing, requires a pre-existing network of semantic knowledge that relies on a widely distributed neural network. The inferior prefrontal cortex (IPFC) has been identified as a vital structure for processing competing semantic information when making a decision about the meaning of a stimulus. However, the precise role of the IPFC in maintaining or creating a consistent semantic organizational structure is unclear. In this study, a semantic triadic decision-making task (Tallent, K.A., Weinberger, D.R., and Goldberg, T.E. 2001. Associating semantic space abnormalities with formal thought disorder in schizophrenia: use of triadic comparisons. J. Clin. Exp. Neuropsychol. 285-296) was used during functional magnetic resonance imaging to test the hypothesis that the degree of activation in the IPFC correlates with the consistency of semantic organization in healthy subjects. In this sample, subjects who had greater activation in the IPFC also demonstrated smaller stress coefficients in a two-dimensional "semantic space", indicating a greater organization of words along semantic dimensions. This finding is consistent with the role of the IPFC in establishing self-generated semantic relationships between stimuli. (c) 2005 Elsevier Inc. All rights reserved. C1 Univ Calif San Diego, Lab Biol Dynam & Theoret Med, La Jolla, CA 92093 USA. Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. Vet Affairs San Diego Heathcare Syst, La Jolla, CA 92161 USA. NIMH, Clin Brain Disorders Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA. RP Paulus, MP (reprint author), Univ Calif San Diego, Lab Biol Dynam & Theoret Med, La Jolla, CA 92093 USA. EM mpaulus@ucsd.edu FU NIDA NIH HHS [R21DA13186]; NIMH NIH HHS [T32-MH18399] NR 25 TC 6 Z9 6 U1 1 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD OCT 15 PY 2005 VL 28 IS 1 BP 30 EP 38 DI 10.1016/j.neuroimage.2005.05.029 PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 974XA UT WOS:000232623500005 PM 16009569 ER PT J AU Luo, H Husain, FT Horwitz, B Poeppel, D AF Luo, H Husain, FT Horwitz, B Poeppel, D TI Discrimination and categorization of speech and non-speech sounds in an MEG delayed-match-to-sample study SO NEUROIMAGE LA English DT Article DE auditory; language; working memory; wavelet; oscillation ID PRIMATE PREFRONTAL CORTEX; WORKING-MEMORY TASK; GAMMA-BAND ACTIVITY; EVENT-RELATED DYNAMICS; VISUAL CATEGORIZATION; FUNCTIONAL MRI; BRAIN ACTIVITY; HUMANS; OSCILLATIONS; PERCEPTION AB We investigated the perception and categorization of speech (vowels, syllables) and non-speech (tones, tonal contours) stimuli using MEG. In a delayed-match-to-sample paradigm, participants listened to two sounds and decided if they sounded exactly the same or different (auditory discrimination, AUD), or if they belonged to the same or different categories (category discrimination, CAT). Stimuli across the two conditions were identical; the category definitions for each kind of sound were learned in a training session before recording. MEG data were analyzed using an induced wavelet transform method to investigate task-related differences in time-frequency patterns. In auditory cortex, for both AUD and CAT conditions, an alpha (8-13 Hz) band activation enhancement during the delay period was found for all stimulus types. A clear difference between AUD and CAT conditions was observed for the non-speech stimuli in auditory areas and for both speech and non-speech stimuli in frontal areas. The results suggest that alpha band activation in auditory areas is related to both working memory and categorization for new non-speech stimuli. The fact that the dissociation between speech and non-speech occurred in auditory areas, but not frontal areas, points to different categorization mechanisms and networks for newly learned (non-speech) and natural (speech) categories. (c) 2005 Elsevier Inc. All rights reserved. C1 Univ Maryland, Neurosci & Cognit Sci Program, College Pk, MD 20742 USA. Univ Maryland, Dept Biol, College Pk, MD 20742 USA. NIDCD, Brain Imaging & Modeling Sect, NIH, Bethesda, MD 20892 USA. Univ Maryland, Dept Linguist, College Pk, MD 20742 USA. RP Luo, H (reprint author), Univ Maryland, Neurosci & Cognit Sci Program, 1401 Marie Mt Hall, College Pk, MD 20742 USA. EM huanl@wam.umd.edu FU Intramural NIH HHS; NIDCD NIH HHS [R01 DC05660] NR 58 TC 21 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 1053-8119 J9 NEUROIMAGE JI Neuroimage PD OCT 15 PY 2005 VL 28 IS 1 BP 59 EP 71 DI 10.1016/j.neuroimage.2005.05.040 PG 13 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 974XA UT WOS:000232623500008 PM 16023868 ER PT J AU Giovacchini, G Lang, LX Ma, Y Herscovitch, P Eckelman, WC Carson, RE AF Giovacchini, G Lang, LX Ma, Y Herscovitch, P Eckelman, WC Carson, RE TI Differential effects of paroxetine on raphe and cortical 5-HT1A binding: A PET study in monkeys SO NEUROIMAGE LA English DT Article DE paroxetine; 5-HT; positron emission tomography ID POSITRON-EMISSION-TOMOGRAPHY; IN-VIVO MICRODIALYSIS; INDUCED DOPAMINE RELEASE; RAT-BRAIN; SEROTONIN TRANSPORTER; EXTRACELLULAR 5-HYDROXYTRYPTAMINE; AUTORADIOGRAPHIC LOCALIZATION; REUPTAKE INHIBITOR; LIGAND F-18-MPPF; FRONTAL-CORTEX AB Positron emission tomography (PET) ligands that are sensitive to transient changes in serotonin (5-HT) concentration are desirable for studies of neuropsychiatric diseases. Few studies, however, have sought to demonstrate that variations in 5-HT concentration can be closely tracked with available serotonergic ligands. Microdialysis studies in rats have shown a maximal increase in 5-HT concentration in raphe nuclei after systemic infusion of selective serotonergic re-uptake inhibitors (SSRIs). We performed PET scans with [F-18]FPWAY, an intermediate-affinity antagonist of 5-HT1A receptors, in 4 anesthetized rhesus monkeys in control studies and after systemic paroxetine administration (5 mg/kg, Lv.). In addition, a paired [C-11]DASB study revealed that this paroxetine regimen produced an occupancy of 54-83% of the serotonin transporters. According to the conventional receptor competition model, increased 5-HT concentration produces decreased binding of the radioactive ligand. Over a 3-h period following paroxetine infusion, a progressively increasing reduction (ranging from 8 +/- 6% to 27 +/- 10%) of [18F]FPWAY-specific binding was found in the raphe nuclei. This result is interpreted as an SSRI-induced increase in 5-HT concentration, potentially combined with reduced binding to internalized 5-HT1A receptors. In addition, a transient (1 h) increase in cerebral cortical binding was observed, attributed primarily to a reduction in cortical 5HT due to the effects of raphe autoreceptor inhibition. This study is the first demonstration of the feasibility of quantifying dynamic changes in 5-HT neurotransmission in the raphe and the cortex with PET. These results lend promise to the use of these serotonergic neuroimaging techniques to study neuropsychiatric disorders. Published by Elsevier Inc. C1 NIH, Clin Ctr, PET Dept, Bethesda, MD 20892 USA. Univ Pisa, Sch Med, Postgrad Special Sch Nucl Med, Pisa, Italy. RP Carson, RE (reprint author), Yale Univ, Sch Med, POB 208042, New Haven, CT 06520 USA. EM richard.e.carson@yale.edu RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 NR 91 TC 21 Z9 22 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD OCT 15 PY 2005 VL 28 IS 1 BP 238 EP 248 DI 10.1016/j.neuroimage.2005.05.042 PG 11 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 974XA UT WOS:000232623500024 PM 15993625 ER PT J AU Ahmad, A Syed, FA Singh, S Hadi, SM AF Ahmad, A Syed, FA Singh, S Hadi, SM TI Prooxidant activity of resveratrol in the presence of copper ions: Mutagenicity in plasmid DNA SO TOXICOLOGY LETTERS LA English DT Article DE resveratrol; polyphenols; copper; prooxidant; anti-cancer; guanine ID CELL-DEATH; APOPTOSIS; CU(II); DAMAGE; MECHANISM; CURCUMIN; GRAPES; CANCER; AGENT; WINE AB Resveratrol, a polyphenolic compound of plant origin, has been of much interest to researchers because of its anticancer and cardiovascular properties. Although antioxidant action of this compound is believed responsible for its reported properties, it has also been shown to exhibit prooxidant properties, especially in the presence of copper ions. Here we report the mutagenicity of resveratrol in plasmid DNA. Plasmid bluescript SK(+) DNA was treated with increasing concentrations of resveratrol in the presence and absence of copper ions, transformed into competent DH5 alpha cells and sequenced. We looked for mutations caused by resveratrol treatment by comparing the sequences of treated plasmids versus control (untreated plasmid). The results show a decrease in the transformation efficiency of the plasmid after resveratrol treatment, and although all types of mutations were recorded, point mutations (deletions/substitutions) were found to be the predominant ones. Resveratrol alone resulted in deletion of mainly guanine bases. Since copper ions are known to be found in the nucleus, bound to guanine bases in chromatin, our results suggest mobilization of such endogenous copper by resveratrol resulting in prooxidant DNA cleavage at the site. Concentration of copper is reported to be elevated in various malignancies and the present studies might explain the reported anticancer activity of resveratrol in various cancer cell lines. (c) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Aligarh Muslim Univ, Fac Life Sci, Dept Biochem, Aligarh 202002, Uttar Pradesh, India. RP Ahmad, A (reprint author), NCI, Lab Immune Cell Biol, NIH, 9000 Rockville Pike,Bldg 37,Rm 3016, Bethesda, MD 20892 USA. EM ahmada@mail.nih.gov RI Ahmad, Aamir/E-8747-2010; OI Ahmad, Aamir/0000-0003-1784-5723 NR 45 TC 37 Z9 38 U1 0 U2 6 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0378-4274 EI 1879-3169 J9 TOXICOL LETT JI Toxicol. Lett. PD OCT 15 PY 2005 VL 159 IS 1 BP 1 EP 12 DI 10.1016/j.toxlet.2005.04.001 PG 12 WC Toxicology SC Toxicology GA 975QJ UT WOS:000232676700001 PM 15913925 ER PT J AU Bielsky, IE Hu, SB Young, LJ AF Bielsky, IE Hu, SB Young, LJ TI Sexual dimorphism in the vasopressin system: Lack of an altered behavioral phenotype in female V1a receptor knockout mice SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE vasopressin; V1a receptor; anxiety; neuropeptides; vasopressin; females; sexual dimorphism ID ANXIETY-RELATED BEHAVIOR; LATERAL SEPTAL VASOPRESSIN; OXYTOCIN-DEFICIENT MICE; BED NUCLEUS; STRIA TERMINALIS; SOCIAL DISCRIMINATION; MONOGAMOUS VOLE; GENE-TRANSFER; RATS; EXPRESSION AB Previous findings with an AVP V1a receptor knockout mouse (V1aRKO) demonstrate a significant role for this receptor in anxiety-like behavior in males. Here we report the lack of anxiety-like effects of the null mutation in female mice. V1aRKO females performed normally on all tests for anxiety-like behavior. This sex difference may be due to the sexual dimorphism in the extra-hypothalamic vasopressin system, with males having significantly more vasopressin fibers in this system. (c) 2005 Published by Elsevier B.V. C1 Emory Univ, Dept Psychiat, Atlanta, GA 30329 USA. Emory Univ, Ctr Behav Neurosci, Atlanta, GA 30329 USA. NIMH, Clin Neuroendocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Bielsky, IE (reprint author), Emory Univ, Dept Psychiat, Atlanta, GA 30329 USA. EM alanwithisa@yahoo.com FU NCRR NIH HHS [RR00165]; NIMH NIH HHS [MH056538, MH070112, MH56897, MH64692] NR 33 TC 53 Z9 54 U1 0 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-4328 J9 BEHAV BRAIN RES JI Behav. Brain Res. PD OCT 14 PY 2005 VL 164 IS 1 BP 132 EP 136 DI 10.1016/j.bbr.2005.06.005 PG 5 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 973IA UT WOS:000232514900017 PM 16046007 ER PT J AU Tong, YH Hara, A Komatsu, M Tanaka, N Kamijo, A Gonzalez, FJ Aoyama, T AF Tong, YH Hara, A Komatsu, M Tanaka, N Kamijo, A Gonzalez, FJ Aoyama, T TI Suppression of expression of muscle-associated proteins by PPAR alpha in brown adipose tissue SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE peroxisome proliferator-activated receptor alpha; brown adipose tissue; synchronous suppression; transcriptional regulation; MALDI-TOF MS ID ACTIVATED RECEPTOR-ALPHA; RAT-LIVER MITOCHONDRIA; CYTOSKELETAL PROTEINS; PURIFICATION; PARVALBUMIN; CELLS; METABOLISM; PROTEOMICS; ENZYMES; ADULT AB Peroxisome proliferator-activated receptor alpha (PPAR alpha) belongs to the steroid/nuclear receptor superfamily. Two-dimensional (2D) SDS-PAGE analysis of brown adipose tissue (BAT) unexpectedly revealed six spots that were, present only in PPAR alpha-null mice. Proteomic analysis indicated that these proteins were tropomyosin-1 alpha chain, tropomyosin beta chain, myosin regulatory light chain 2, myosin light chain 3, and parvalbumin alpha. Analyses of mRNA have revealed that PPAR alpha suppressed the genes encoding these proteins in a synchronous manner in adult wild-type mice. Histological and physiological analyses of BAT showed in adult wild-type mice, a marked suppression of BAT growth concurrent with a prominent decrease in lipolytic and thermogenesis activities. These results suggest that in adult mice, PPAR alpha functions to suppress the expression of the proteins that may be involved in the architecture of BAT, and thus may function in keeping BAT in a quiescent state. (c) 2005 Elsevier Inc. All rights reserved. C1 Shinshu Univ, Grad Sch Med, Inst Aging & Adaptat, Dept Metab Regulat, Nagano 3908621, Japan. Shinshu Univ, Sch Med, Dept Internal Med, Matsumoto, Nagano 3908621, Japan. NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. RP Hara, A (reprint author), Shinshu Univ, Grad Sch Med, Inst Aging & Adaptat, Dept Metab Regulat, 3-1-1 Asahi, Nagano 3908621, Japan. EM kareisei@sch.md.shinshu-u.ac.jp RI Hara, Atsushi/B-1127-2008 NR 26 TC 12 Z9 15 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD OCT 14 PY 2005 VL 336 IS 1 BP 76 EP 83 DI 10.1016/j.bbrc.2005.08.041 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 965HP UT WOS:000231941500013 PM 16125138 ER PT J AU Sasaki, CY Barberi, TJ Ghosh, P Longo, DL AF Sasaki, CY Barberi, TJ Ghosh, P Longo, DL TI Phosphorylation of RelA/p65 on serine 536 defines an I kappa B alpha-independent NF-kappa B pathway SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID NECROSIS-FACTOR-ALPHA; NUCLEAR-FACTOR; P65 SUBUNIT; TRANSCRIPTIONAL ACTIVATION; IKK-BETA; T-CELLS; KINASE; GENE; MECHANISM; PROTEIN AB The association of the NF-kappa B p65/p50 dimer with I kappa B alpha plays a pivotal role in regulating its nuclear translocation and gene transcription. In addition, serine phosphorylation at various sites of the p65 subunit has been shown to be important in initiating transcription. Here we demonstrate that the regulation of nuclear translocation of p65 phosphorylated at serine 536 is not dependent on I kappa B alpha. Stimulation of either Jurkat or normal human T cells resulted in the nuclear translocation of phospho-p65 (Ser(536)). In addition, the phospho-p65 (Ser(536)) was not associated with either I kappa B alpha or p50, and the nuclear translocation of phospho-p65 (Ser(536)), but not total p65, was unaffected by the proteosome inhibitor MG-132, which blocks I kappa B protein degradation and prevents p65/p50 dimer nuclear translocation. Accordingly, the co-expression of a dominant negative mutant of I kappa B alpha blocked the transcriptional activity mediated by wild type but not the dominant positive p65 mutant (S536D). Furthermore, the transfection of the S536D form of p65 led to the induction of interleukin-8 transcription following stimulation, whereas the S536A form, which cannot be phosphorylated at this site, did not. Together, the findings suggest that p65 phosphorylated on serine 536 is not associated with or regulated by I kappa B alpha, that it has a distinct set of target genes, and that it may represent a noncanonical NF-kappa B pathway that is independent of I kappa B alpha regulation. C1 NIA, Immunol Lab, NIH, Baltimore, MD 21224 USA. RP Sasaki, CY (reprint author), NIA, Immunol Lab, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM sasakic@grc.nia.nih.gov NR 46 TC 181 Z9 182 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 14 PY 2005 VL 280 IS 41 BP 34538 EP 34547 DI 10.1074/jbc.M504943200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 971SD UT WOS:000232403900022 PM 16105840 ER PT J AU Knight, PJ Thirumurugan, K Xu, YH Wang, F Kalverda, AP Stafford, WF Sellers, JR Peckham, M AF Knight, PJ Thirumurugan, K Xu, YH Wang, F Kalverda, AP Stafford, WF Sellers, JR Peckham, M TI The predicted coiled-coil domain of myosin 10 forms a novel elongated domain that lengthens the head SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN SECONDARY STRUCTURE; LARGE STEP-SIZE; UNCONVENTIONAL MYOSINS; ION-PAIRS; STABILITY; HELIX; VI; PROCESSIVITY; COEFFICIENTS; SEQUENCES AB Myosin 10 contains a region of predicted coiled coil 120 residues long. However, the highly charged nature and pattern of charges in the proximal 36 residues appear incompatible with coiled-coil formation. Circular dichroism, NMR, and analytical ultracentrifugation show that a synthesized peptide containing this region forms a stable single alpha-helix (SAH) domain in solution and does not dimerize to form a coiled coil even at millimolar concentrations. Additionally, electron microscopy of a recombinant myosin 10 containing the motor, the three calmodulin binding domains, and the full-length predicted coiled coil showed that it was mostly monomeric at physiological protein concentration. In dimers the molecules were joined only at their extreme distal ends, and no coiled-coil tail was visible. Furthermore, the neck lengths of both monomers and dimers were much longer than expected from the number of calmodulin binding domains. In contrast, micrographs of myosin 5 heavy meromyosin obtained under the same conditions clearly showed a coiled-coil tail, and the necks were the predicted length. Thus the predicted coiled coil of myosin 10 forms a novel elongated structure in which the proximal region is a SAH domain and the distal region is a SAH domain ( or has an unknown extended structure) that dimerizes only at its end. Sequence comparisons show that similar structures may exist in the predicted coiled-coil domains of myosins 6 and 7a and MyoM and could function to increase the size of the working stroke. C1 Univ Leeds, Sch Biomed Sci, Leeds LS2 9JT, W Yorkshire, England. Univ Leeds, Astbury Ctr Struct Mol Biol, Leeds LS2 9JT, W Yorkshire, England. Univ Leeds, Sch Biochem & Microbiol, Leeds LS2 9JT, W Yorkshire, England. Boston Biomed Res Inst, Analyt Ultracentrifugat Res Lab, Boston, MA 02472 USA. NHLBI, Lab Mol Physiol, NIH, Bethesda, MD 20892 USA. RP Peckham, M (reprint author), Univ Leeds, Sch Biomed Sci, Worsley Bldg, Leeds LS2 9JT, W Yorkshire, England. EM m.peckham@leeds.ac.uk RI Peckham, Michelle/J-4991-2015; OI Peckham, Michelle/0000-0002-3754-2028; Thirumurugan, Kavitha/0000-0002-4673-4099 FU Biotechnology and Biological Sciences Research Council [BB/C004906/1]; Wellcome Trust NR 30 TC 95 Z9 96 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 14 PY 2005 VL 280 IS 41 BP 34702 EP 34708 DI 10.1074/jbc.M504887200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 971SD UT WOS:000232403900040 PM 16030012 ER PT J AU Han, SJ Hamdan, FF Kim, SK Jacobson, KA Bloodworth, LM Li, B Wess, J AF Han, SJ Hamdan, FF Kim, SK Jacobson, KA Bloodworth, LM Li, B Wess, J TI Identification of an agonist-induced conformational change occurring adjacent to the ligand-binding pocket of the M-3 muscarinic acetylcholine receptor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-COUPLED RECEPTORS; BETA(2) ADRENERGIC-RECEPTOR; DISULFIDE CROSS-LINKING; SITE-DIRECTED MUTAGENESIS; TRANSMEMBRANE DOMAINS III; 7-TRANSMEMBRANE RECEPTORS; CONSTITUTIVE ACTIVATION; SCANNING MUTAGENESIS; RHODOPSIN STRUCTURE; TYROSINE RESIDUES AB To study the conformational changes that convert G protein-coupled receptors (GPCRs) from their resting to their active state, we used the M-3 muscarinic acetylcholine receptor, a prototypical class A GPCR, as a model system. Specifically, we employed a recently developed in situ disulfide cross-linking strategy that allows the formation of disulfide bonds in Cys-substituted mutant M-3 muscarinic receptors present in their native membrane environment. At present, little is known about the conformational changes that GPCR ligands induce in the immediate vicinity of the ligand-binding pocket. To address this issue, we generated 11 Cys-substituted mutant M-3 muscarinic receptors and characterized these receptors in transfected COS-7 cells. All analyzed mutant receptors contained an endogenous Cys residue (Cys-532(7.42)) located within the exofacial segment of transmembrane domain (TM) VII, close to the agonist-binding site. In addition, all mutant receptors harbored a second Cys residue that was introduced into the exofacial segment of TM III, within the sequence Leu-142(3.27)-Asn-152(3.37). Disulfide cross-linking studies showed that muscarinic agonists, but not antagonists, promoted the formation of a disulfide bond between S151(3.36)C and Cys-532. A three-dimensional model of the inactive state of the M-3 muscarinic receptor indicated that Cys-532 and Ser-151 face each other in the center of the TM receptor core. Our cross-linking data therefore support the concept that agonist activation pulls the exofacial segments of TMs VII and III closer to each other. This structural change may represent one of the early conformational events triggering the more pronounced structural reorganization of the intracellular receptor surface. To the best of our knowledge, this is the first direct demonstration of a conformational change occurring in the immediate vicinity of the binding site of a GPCR activated by a diffusible ligand. C1 NIDDK, Mol Signaling Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Wess, J (reprint author), NIDDK, Mol Signaling Sect, Bioorgan Chem Lab, NIH, Bldg 8A,Rm B1A-05,MSC 0810, Bethesda, MD 20892 USA. EM jwess@helix.nih.gov RI Jacobson, Kenneth/A-1530-2009; Han, Sung-Jun/B-9547-2012 OI Jacobson, Kenneth/0000-0001-8104-1493; NR 59 TC 37 Z9 38 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 14 PY 2005 VL 280 IS 41 BP 34849 EP 34858 DI 10.1074/jbc.M506711200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 971SD UT WOS:000232403900057 PM 16093246 ER PT J AU Levrand, S Pesse, B Feihl, F Waeber, B Pacher, P Rolli, J Schaller, MD Liaudet, L AF Levrand, S Pesse, B Feihl, F Waeber, B Pacher, P Rolli, J Schaller, MD Liaudet, L TI Peroxynitrite is a potent inhibitor of NF-kappa B activation triggered by inflammatory stimuli in cardiac and endothelial cell lines SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LYMPHOTOXIN-BETA-RECEPTOR; HYDROGEN-PEROXIDE; NITRIC-OXIDE; IKK-ALPHA; MYOCARDIAL DYSFUNCTION; SYSTEMIC INFLAMMATION; GENE-EXPRESSION; KINASE-ACTIVITY; PHOSPHORYLATION; PATHWAYS AB Peroxynitrite is a potent oxidant and nitrating species proposed as a direct effector of myocardial damage in numerous cardiac pathologies. Whether peroxynitrite also acts indirectly, by modulating cell signal transduction in the myocardium, has not been investigated. Therefore, we examined a possible role for peroxynitrite on the activation of NF-kappa B, a crucial pro-inflammatory transcription factor, in cultured H9C2 cardiomyocytes. H9C2 cells were stimulated with tumor necrosis factor-alpha or lipopolysaccharide following a brief (20-min) exposure to peroxynitrite. NF-kappa B activation ( phosphorylation and degradation of its inhibitor I kappa B alpha, nuclear translocation of NF-kappa B p65, and NF-kappa B DNA binding) triggered by lipopolysaccharide or tumor necrosis factor-alpha was abrogated by peroxynitrite. Peroxynitrite also inhibited NF-kappa B in two human endothelial cell lines activated with tumor necrosis factor-alpha or interleukin-1 beta. These effects were related to oxidative but not nitrative chemistry and were still being observed while nitration was suppressed by epicatechin. The mechanism of NF-kappa B inhibition by peroxynitrite was a complete blockade of phosphorylation and activation of the upstream kinase I kappa B kinase (IKK) beta, required for canonical, pro-inflammatory NF-kappa B activation. At the same time, peroxynitrite activated phosphorylation of NF-kappa B-inducing kinase and IKK alpha, considered as part of an alternative, noncanonical NF-kappa B activation pathway. Suppression of IKK beta-dependent NF-kappa B activation translated into a marked inhibition of the transcription of NF-kappa B-dependent genes by peroxynitrite. Thus, peroxynitrite has a dual effect on NF-kappa B, inhibiting canonical IKK beta-dependent NF-kappa B activation while activating NF-kappa B-inducing kinase and IKK alpha phosphorylation, which suggests its involvement in an alternative pathway of NF-kappa B activation. These findings offer new perspectives for the understanding of the relationships between redox stress and inflammation. C1 Univ Lausanne Hosp, Dept Internal Med, Div Crit Care, CH-1011 Lausanne, Switzerland. Univ Lausanne Hosp, Dept Internal Med, Div Clin Pathophysiol, CH-1011 Lausanne, Switzerland. NIAAA, Lab Physiol Studies, Bethesda, MD 20892 USA. RP Liaudet, L (reprint author), Univ Lausanne Hosp, Dept Internal Med, Div Crit Care, CH-1011 Lausanne, Switzerland. EM Lucas.Liaudet@chuv.hospvd.ch RI Pacher, Pal/B-6378-2008; Liaudet, Lucas/E-1322-2017 OI Pacher, Pal/0000-0001-7036-8108; Liaudet, Lucas/0000-0003-2670-4930 FU Intramural NIH HHS [Z01 AA000375-02] NR 41 TC 44 Z9 47 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 14 PY 2005 VL 280 IS 41 BP 34878 EP 34887 DI 10.1074/jbc.M501977200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 971SD UT WOS:000232403900060 PM 16079150 ER PT J AU Yang, TX Zhang, AH Honeggar, M Kohan, DE Mizel, D Sanders, K Hoidal, JR Briggs, JP Schnermann, JB AF Yang, TX Zhang, AH Honeggar, M Kohan, DE Mizel, D Sanders, K Hoidal, JR Briggs, JP Schnermann, JB TI Hypertonic induction of COX-2 in collecting duct cells by reactive oxygen species of mitochondrial origin SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID OSMOTIC RESPONSE ELEMENT; CHRONIC GRANULOMATOUS-DISEASE; MEDULLARY INTERSTITIAL-CELLS; CYCLOOXYGENASE-2 EXPRESSION; NADPH OXIDASE; TYROSINE PHOSPHORYLATION; PROSTAGLANDIN SYNTHESIS; MAMMALIAN-CELLS; RABBIT KIDNEY; P38 KINASE AB Our previous studies have documented MAPK mediation of the hypertonicity-induced stimulation of COX-2 expression in cultured renal medullary epithelial cells (Yang, T., Huang, Y., Heasley, L. E., Berl, T., Schnermann, J. B., and Briggs, J. P. (2000) J. Biol. Chem. 275, 23281-23286). The present study extends this observation by examining the role of reactive oxygen species (ROSs). ROS levels, determined using dichlorodihydrofluorescence diacetate and cytochrome c, were rapidly and significantly increased following exposure of mIMCD-K2 cells to media made hypertonic by adding NaCl. Hypertonic treatment (550 mosmol/kg) for 16 h induced a 5.6-fold increase in COX-2 protein levels and comparable increases in prostaglandin E-2 release, both of which were completely abolished by the NADPH oxidase inhibitor diphenyleneiodonium (25-50 mu M). The general antioxidant N-acetyl-L-cysteine (6 mM), and the superoxide dismutase mimetic TEMPO (2.0 mM) reduced COX-2 levels by 75.6 and 79.8%, respectively. Exposure of mIMCD-K2 cells to exogenous O-2(-center dot) generated by the xanthine/xanthine oxidase system mimicked the effect of hypertonicity on COX-2 expression and prostaglandin E2 release. The increases in phosphorylation of ERK1/2 and p38 were detected 20 min following the hypertonic treatment and were both prevented by N-acetyl-L-cysteine. The increases in ROSs in response to hypertonic treatment were completely blocked by any one of the mitochondrial inhibitors tested, such as rotenone, thenoyltrifluoroacetone, or carbonyl cyanide m-chlorophenylhydrazone, associated with remarkable inhibition of COX-2 expression. In contrast, the increases in ROSs were not significantly altered in IMCD cells deficient in either gp91(phox) or p47(phox), nor were the increases in COX-2 expression. We conclude that ROSs derived from mitochondria, but not NADPH oxidase, mediate the hypertonicity-induced phosphorylation of MAPK and the stimulation of COX-2 expression. C1 Univ Utah, Res Serv 151 E, Dept Internal Med, Salt Lake City, UT 84148 USA. Vet Affairs Med Ctr, Res Serv 151 E, Salt Lake City, UT 84148 USA. NIDDK, NIH, Bethesda, MD 20892 USA. RP Yang, TX (reprint author), Univ Utah, Res Serv 151 E, Dept Internal Med, Bldg 2,500 Foothill Dr, Salt Lake City, UT 84148 USA. EM tianxin.yang@hsc.utah.edu RI Briggs, Josephine/B-9394-2009 OI Briggs, Josephine/0000-0003-0798-1190 FU NHLBI NIH HHS [R01 HL079453]; NIDDK NIH HHS [R01 DK066592, K01 DK064981, R21 DK069490] NR 42 TC 53 Z9 54 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 14 PY 2005 VL 280 IS 41 BP 34966 EP 34973 DI 10.1074/jbc.M502430200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 971SD UT WOS:000232403900070 PM 16024921 ER PT J AU Ramasamy, V Ramakrishnan, B Boeggeman, E Ratner, DM Seeberger, PH Qasba, PK AF Ramasamy, V Ramakrishnan, B Boeggeman, E Ratner, DM Seeberger, PH Qasba, PK TI Oligosaccharide preferences of beta 1,4-galactosyltransferase-I: Crystal structures of Met340His mutant of human beta 1,4-galactosyltransferase-I with a pentasaccharide and trisaccharides of the N-glycan moiety SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE beta-1,4-galactosyltransferase-I; conformational change; N-glycan trisaccharides; human-beta 4Gal-T1-oligosaccharide crystal structures; beta 4Gal-T1 oligosaccharide preferences ID BOVINE BETA-1,4-GALACTOSYLTRANSFERASE; CATALYTIC DOMAIN; UDP-GALACTOSE; COMPLEX; GALACTOSYLTRANSFERASE; GLYCOSYLTRANSFERASES; CRYSTALLOGRAPHY; GLYCOPEPTIDES; SPECIFICITY; MOLSCRIPT AB beta-1,4-Galactosyltransferase-I (beta 4Gal-T1) transfers galactose from UDPgalactose to N-acetylglucosamine (GlcNAc) residues of the branched N-linked oligosaccharide chains of glycoproteins. In an N-linked biantennary oligosaccharide chain, one antenna is attached to the 3-hydroxyl-(1,3-arm), and the other to the 6-hydroxyl-(1,6-arm) group of mannose, which is beta-1,4-linked to an N-linked chitobiose, attached to the aspargine residue of a protein. For a better understanding of the branch specificity of beta 4Gal-T1 towards the GlcNAc residues of N-glycans, we have carried out kinetic and crystallographic studies with the wild-type human beta 4Gal-T1 (h-beta 4Gal-T1) and the mutant Met340His-beta 4Gal-T1 (h-M340H-beta 4Gal-T1) in complex with a GlcNAc-containing pentasaccharide and several GlcNAc-containing trisaccharides present in N-glycans. The oligosaccharides used were: pentasaccharide GlcNAc beta 1,2-Man alpha 1,6 (GlcNAc beta 1,2-Man alpha 1,3)Man; the 1,6-arm trisaccharide, GlcNAc beta 1,2-Man alpha 1,6-Man beta-OR (1,2-1,6-arm); the 1,3-arm trisaccharides, GlcNAc beta 1,2-Man alpha 1,3-Man beta-OR (1,2-1,3-arm) and GlcNAc beta 1,4-Man alpha 1,3-Man beta-OR (1,4-1,3-arm); and the trisaccharide GlcNA beta 1,4-GlcNAc beta 1,4-GlcNAc (chitotriose). With the wild-type h-beta 4Gal-T1, the K, of 1,2-1,6-arm is approximately tenfold lower than for 1,2-1,3arm and 1,4-1,3-arm, and 22-fold lower than for chitotriose. Crystal structures of h-M340H-P beta Gal-T1 in complex with the pentasaccharide and various trisaccharides at 1.9-2.0 angstrom resolution showed that beta 4Gal-T1 is in a closed conformation with the oligosaccharide bound to the enzyme, and the 1,2-1,6-arm trisaccharide makes the maximum number of interactions with the enzyme, which is in concurrence with the lowest K, for the trisaccharide. Present studies suggest that beta 4Gal-T1 interacts preferentially with the 1,2-1,6-arm trisaccharide rather than with the 1,2-1,3-arm or 1,4-1, 3-arm of a bi- or tri-antennary oligosaccharide chain of N-glycan. Published by Elsevier Ltd. C1 NCI, Struct Glycobiol Sect, Lab Expt & Computat Biol, Ctr Canc Res, Frederick, MD 21702 USA. SAIC Frederick Inc, Basic Res Program, Frederick, MD 21702 USA. MIT, Dept Chem, Cambridge, MA 02139 USA. ETH Honggerberg, HCI, Organ Chem Lab, CH-8093 Zurich, Switzerland. RP Qasba, PK (reprint author), NCI, Struct Glycobiol Sect, Lab Expt & Computat Biol, Ctr Canc Res, Frederick, MD 21702 USA. EM qasba@helix.nih.gov FU Intramural NIH HHS; PHS HHS [N01-C0-12400] NR 40 TC 22 Z9 23 U1 1 U2 3 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD OCT 14 PY 2005 VL 353 IS 1 BP 53 EP 67 DI 10.1016/j.jmb.2005.07.050 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 972AT UT WOS:000232426900005 PM 16157350 ER PT J AU Phan, J Shi, ZD Burke, TR Waugh, DS AF Phan, J Shi, ZD Burke, TR Waugh, DS TI Crystal structures of a high-affinity macrocyclic peptide mimetic in complex with the Grb2 SH2 domain SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE Grb2 SH2; domain-swapped; macrocyclic tetrapeptide mimetic S1s; drug design ID STRUCTURE-BASED DESIGN; PHOSPHOTYROSINE-CONTAINING PEPTIDE; TYROSINE KINASE; ADAPTER PROTEINS; BINDING LIGANDS; INHIBITORS; REPLACEMENT; MODE; REQUIREMENTS; RECOGNITION AB The high-affinity binding of the growth factor receptor-bound protein 2 (Grb2) SH2 domain to tyrosine-phosphorylated cytosolic domains of receptor tyrosine kinases (RTKs) is an attractive target for therapeutic intervention in many types of cancer. We report here two crystal forms of a complex between the Grb2 SH2 domain and a potent non-phosphorus-containing macrocyclic peptide mimetic that exhibits significant antiproliferative effects against erbB-2-dependent breast cancers. This agent represents a "second generation" inhibitor with greatly,improved binding affinity and bio-availability compared to its open-chain counterpart. The structures were determined at 2.0 angstrom and 1.8 angstrom with one and two domain-swapped dimers per asymmetric unit, respectively. The mode of binding and specific interactions between the protein and the inhibitor provide insight into the high potency, of this class of macrocylic compounds and may aid in further optimization as part of the iterative rational drug design process. Published by Elsevier Ltd. C1 NCI, Macromol Crystallog Lab, Ctr Canc Res, Frederick, MD 21702 USA. NCI, Lab Med Chem, Ctr Canc Res, Frederick, MD 21702 USA. RP Waugh, DS (reprint author), NCI, Macromol Crystallog Lab, Ctr Canc Res, POB B, Frederick, MD 21702 USA. EM waughd@ncifcrf.gov RI Burke, Terrence/N-2601-2014 FU Intramural NIH HHS NR 44 TC 19 Z9 20 U1 1 U2 3 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD OCT 14 PY 2005 VL 353 IS 1 BP 104 EP 115 DI 10.1016/j.jmb.2005.08.037 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 972AT UT WOS:000232426900009 PM 16165154 ER PT J AU Yamazaki, Y Kakizaki, S Horiguchi, N Takagi, H Mori, M Negishi, M AF Yamazaki, Yuichi Kakizaki, Satoru Horiguchi, Norio Takagi, Hitoshi Mori, Masatomo Negishi, Masahiko TI Role of nuclear receptor CAR in carbon tetrachloride-induced hepatotoxicity SO WORLD JOURNAL OF GASTROENTEROLOGY LA English DT Article DE CAR; Phenobarbital; Cytochrome P450; CCl4; Drug-induced liver injury AB AIM: To investigate the precise roles of CAR in CCl4-induced acute hepatotoxicity. METHODS: To prepare an acute liver injury model, CCl4 was intraperitoneally injected in CAR(+/+) and CAR(-/-) mice. RESULTS: Elevation of serum alanine aminotransferase and extension of centrilobular necrosis were slightly inhibited in CAR(-/-) mice compared to CAR(+/+) mice without PB. Administration of a CAR inducer, PB, revealed that CCl4-induced liver toxicity was partially inhibited in CAR(-/-) mice compared with CAR(+/+) mice. On the other hand, androstanol, an inverse agonist ligand, inhibited hepatotoxicity in CAR(+/+) but not in CAR(-/-) mice. Thus, CAR activation caused CCl4 hepatotoxicity while CAR inhibition resulted in partial protection against CCl4-induced hepatotoxicity. There were no differences in the expression of CYP2E1, the main metabolizing enzyme for CCl4, between CAR(+/+) and CAR(-/-)mice. However, the expression of other CCl4-metabolizing enzymes, such as CYP2B10 and 3A11, was induced by PB in CAR(+/+) but not in CAR(-/-) mice. Although the main pathway of CCl4-induced acute liver injury is mediated by CYP2E1, CAR modulates its pathway via induction of CYP2B10 and 3A11 in the presence of activator or inhibitor. CONCLUSION: The nuclear receptor CAR modulates CCl4-induced liver injury via induction of CCl4-metabolizing enzymes in the presence of an activator. Our results suggest that drugs interacting with nuclear receptors such as PB might play critical roles in drug-induced liver injury or drugdrug interaction even though such drugs themselves are not hepatotoxic. (C) 2005 The WJG Press and Elsevier Inc. All rights reserved. C1 [Yamazaki, Yuichi; Kakizaki, Satoru; Horiguchi, Norio; Takagi, Hitoshi; Mori, Masatomo] Gunma Univ, Grad Sch Med, Dept Med & Mol Sci, Maebashi, Gumma 3718511, Japan. [Negishi, Masahiko] NIEHS, Pharmacogenet Sect, Lab Reprod & Dev Toxicol, NIH, Res Triangle Pk, NC 27709 USA. RP Kakizaki, S (reprint author), Gunma Univ, Grad Sch Med, Dept Med & Mol Sci, 3-39-15 Showa Machi, Maebashi, Gumma 3718511, Japan. EM kakizaki@showa.gunma-u.ac.jp FU Ministry of Education, Science, Sports and Culture of the Japanese Government [15790337] FX Supported by a Grant-in Aid for Scientific Research, No. 15790337 from the Ministry of Education, Science, Sports and Culture of the Japanese Government NR 32 TC 11 Z9 12 U1 0 U2 1 PU BAISHIDENG PUBL GRP CO LTD PI BEIJING PA RM 903, BLDG D, OCEAN INTERNATIONAL CTR, NO 62 DONGSIHUAN ZHONGLU, BEIJING, CHAOYANG DISTRICT 100025, PEOPLES R CHINA SN 1007-9327 J9 WORLD J GASTROENTERO JI World J. Gastroenterol. PD OCT 14 PY 2005 VL 11 IS 38 BP 5966 EP 5972 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA V23GJ UT WOS:000208331000009 PM 16273607 ER PT J AU Zerhouni, E AF Zerhouni, E TI NIH moved quickly to help researchers after Katrina SO NATURE LA English DT Letter C1 NIH, Bethesda, MD 20892 USA. RP Zerhouni, E (reprint author), NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD OCT 13 PY 2005 VL 437 IS 7061 BP 951 EP 951 DI 10.1038/437951c PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 973AU UT WOS:000232496100019 PM 16222274 ER PT J AU Shankaran, S Laptook, AR Ehrenkranz, RA Tyson, JE McDonald, SA Donovan, EF Fanaroff, AA Poole, WK Wright, LL Higgins, RD Finer, NN Carlo, WA Duara, S Oh, W Cotten, CM Stevenson, DK Stoll, BJ Lemons, JA Guillet, R Jobe, AH AF Shankaran, S Laptook, AR Ehrenkranz, RA Tyson, JE McDonald, SA Donovan, EF Fanaroff, AA Poole, WK Wright, LL Higgins, RD Finer, NN Carlo, WA Duara, S Oh, W Cotten, CM Stevenson, DK Stoll, BJ Lemons, JA Guillet, R Jobe, AH CA Natl Inst Child Hlth Human Dev Neo TI Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CEREBRAL BLOOD-FLOW; POSTISCHEMIC HYPOTHERMIA; BRAIN TEMPERATURE; NEURONAL DAMAGE; SELECTIVE HEAD; POSTHYPOXIC HYPOTHERMIA; MODERATE HYPOTHERMIA; PERINATAL ASPHYXIA; MILD HYPOTHERMIA; CARDIAC-ARREST AB BACKGROUND: Hypothermia is protective against brain injury after asphyxiation in animal models. However, the safety and effectiveness of hypothermia in term infants with encephalopathy is uncertain. METHODS: We conducted a randomized trial of hypothermia in infants with a gestational age of at least 36 weeks who were admitted to the hospital at or before six hours of age with either severe acidosis or perinatal complications and resuscitation at birth and who had moderate or severe encephalopathy. Infants were randomly assigned to usual care (control group) or whole-body cooling to an esophageal temperature of 33.5 degreesC for 72 hours, followed by slow rewarming (hypothermia group). Neurodevelopmental outcome was assessed at 18 to 22 months of age. The primary outcome was a combined end point of death or moderate or severe disability. RESULTS: Of 239 eligible infants, 102 were assigned to the hypothermia group and 106 to the control group. Adverse events were similar in the two groups during the 72 hours of cooling. Primary outcome data were available for 205 infants. Death or moderate or severe disability occurred in 45 of 102 infants (44 percent) in the hypothermia group and 64 of 103 infants (62 percent) in the control group (risk ratio, 0.72; 95 percent confidence interval, 0.54 to 0.95; P=0.01). Twenty-four infants (24 percent) in the hypothermia group and 38 (37 percent) in the control group died (risk ratio, 0.68; 95 percent confidence interval, 0.44 to 1.05; P=0.08). There was no increase in major disability among survivors; the rate of cerebral palsy was 15 of 77 (19 percent) in the hypothermia group as compared with 19 of 64 (30 percent) in the control group (risk ratio, 0.68; 95 percent confidence interval, 0.38 to 1.22; P=0.20). CONCLUSIONS: Whole-body hypothermia reduces the risk of death or disability in infants with moderate or severe hypoxic-ischemic encephalopathy. C1 Wayne State Univ, Div Neonatal Perinatal Med, Detroit, MI USA. Women & Infants Hosp Rhode Isl, Providence, RI 02908 USA. Yale Univ, Sch Med, New Haven, CT USA. Univ Texas, Houston, TX USA. Res Triangle Inst, Res Triangle Pk, NC 27709 USA. Univ Cincinnati, Coll Med, Cincinnati, OH USA. Case Western Reserve Univ, Rainbow Babies & Childrens Hosp, Cleveland, OH 44106 USA. NICHHD, Bethesda, MD 20892 USA. Univ Calif San Diego, San Diego, CA 92103 USA. Univ Alabama, Birmingham, AL USA. Univ Miami, Dept Pediat, Miami, FL 33152 USA. Duke Univ, Med Ctr, Durham, NC USA. Stanford Univ, Sch Med, Palo Alto, CA 94304 USA. Emory Univ, Sch Med, Atlanta, GA USA. Indiana Univ, Sch Med, Indianapolis, IN USA. Univ Rochester, Rochester, NY USA. RP Shankaran, S (reprint author), Wayne State Univ, Childrens Hosp Michigan, Div Neonatal Perinatal Med, 3901 Beaubien Blvd,Rm 4H46, Detroit, MI 48201 USA. EM sshankar@med.wayne.edu FU NCRR NIH HHS [5 M01 RR00044, M01 RR 00039, M01 RR 00070, M01 RR 00125, M01 RR 0039-43, M01 RR 00750, M01 RR 08084]; NICHD NIH HHS [U10 HD27856, U01 HD36790, U10 HD021385, U10 HD21373, U10 HD21385, U10 HD21397, U10 HD27851, U10 HD27853, U10 HD27871, U10 HD27880, U10 HD27904, U10 HD34216, U10 HD40461, U10 HD40492, U10 HD40498, U10 HD40521, U10 HD40689] NR 35 TC 1132 Z9 1179 U1 6 U2 37 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 13 PY 2005 VL 353 IS 15 BP 1574 EP 1584 DI 10.1056/NEJMcps050929 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 972XF UT WOS:000232486000011 PM 16221780 ER PT J AU Zerhouni, EA AF Zerhouni, EA TI Translational and clinical science - Time for a new vision SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 NIH, Bethesda, MD 20892 USA. RP Zerhouni, EA (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 1 TC 351 Z9 367 U1 2 U2 21 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 13 PY 2005 VL 353 IS 15 BP 1621 EP 1623 DI 10.1056/NEJMsb053723 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 972XF UT WOS:000232486000020 PM 16221788 ER PT J AU Carroll, MD Lacher, DA Sorlie, PD Cleeman, JI Gordon, DJ Wolz, M Grundy, SM Johnson, CL AF Carroll, MD Lacher, DA Sorlie, PD Cleeman, JI Gordon, DJ Wolz, M Grundy, SM Johnson, CL TI Trends in serum lipids and lipoproteins of adults, 1960-2002 SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID EDUCATION-PROGRAM RECOMMENDATIONS; TOTAL CHOLESTEROL CONCENTRATIONS; NUTRITION EXAMINATION SURVEYS; CORONARY-HEART-DISEASE; EXCESS BODY-WEIGHT; NATIONAL-HEALTH; US ADULTS; PRAVASTATIN; PREVENTION; EVENTS AB Context Serum total and low-density lipoprotein (LDL) cholesterol contribute significantly to atherosclerosis and its clinical sequelae. Previous analyses of data from the National Health and Nutrition Examination Surveys (NHANES) showed that mean levels of total cholesterol of US adults had declined from 1960-1962 to 1988-1994, and mean levels of LDL cholesterol (available beginning in 1976) had declined between 1976-1980 and 1988-1994. Objective To examine trends in serum lipid levels among US adults between 1960 and 2002, with a particular focus on changes since the 1988-1994 NHANES survey. Design, Setting, and Participants Blood lipid measurements taken from 6098 to 15 719 adults who were examined in 5 distinct cross-sectional surveys of the US population during 1960-1962, 1971-1974, 1976-1980, 1988-1994, and 1999-2002. Main Outcome Measures Mean serum total cholesterol, LDL cholesterol, high-density lipoprotein (HDL) cholesterol, and geometric mean serum triglyceride levels, and the percentage of adults with a serum total cholesterol level of at least 240 mg/dL (>= 6.22 mmol/L). Results Between 1988-1994 and 1999-2002, total serum cholesterol level of adults aged 20 years or older decreased from 206 mg/dL (5.34 mmol/L) to 203 mg/dL (5.26 mmol/L) (P=.009) and LDL cholesterol levels decreased from 129 mg/dL (3.34 mmol/L) to 123 mg/dL (3.19 mmol/L) (P<.001). Greater and significant decreases were observed in men 60 years or older and in women 50 years or older. The percentage of adults with a total cholesterol level of at least 240 mg/dL (>= 6.22 mmol/L) decreased from 20% during 1988-1994 to 17% during 1999-2002 (P<.001). There was no change in mean HDL cholesterol levels and a nonsignificant increase in geometric mean serum triglyceride levels (P=.06). Conclusions The decrease in total cholesterol level observed during 1960-1994 and LDL cholesterol level observed during 1976-1994 has continued during 1999-2002 in men 60 to 74 years and women 50 to 74 years. The target value of no more than 17% of US adults with a total cholesterol level of at least 240 mg/dL (>= 6.22 mmol/L), an objective of Healthy People 2010, has been attained. The increase in the proportion of adults using lipid-lowering medication, particularly in older age groups, likely contributed to the decreases in total and LDL cholesterol levels observed. The increased prevalence of obesity in the US population may have contributed to the increase in mean serum triglyceride levels. C1 Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA. NHLBI, NIH, Bethesda, MD 20892 USA. Univ Texas, SW Med Ctr, Dallas, TX USA. RP Carroll, MD (reprint author), Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, 3311 Toledo Rd,Room 4413, Hyattsville, MD 20782 USA. EM mdc3@cdc.gov NR 58 TC 289 Z9 295 U1 1 U2 10 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD OCT 12 PY 2005 VL 294 IS 14 BP 1773 EP 1781 DI 10.1001/jama.294.14.1773 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 972RX UT WOS:000232472000016 PM 16219880 ER PT J AU Liu, GM Martins, I Wemmie, JA Chiorini, JA Davidson, BL AF Liu, GM Martins, I Wemmie, JA Chiorini, JA Davidson, BL TI Functional correction of CNS phenotypes in a lysosomal storage disease model using adeno-associated virus type 4 vectors SO JOURNAL OF NEUROSCIENCE LA English DT Article DE lysosomal storage disease; mucopolysaccharidoses; beta-glucuronidase; AAV4; CSF; perivascular; fear conditioning ID MUCOPOLYSACCHARIDOSIS TYPE-VII; CENTRAL-NERVOUS-SYSTEM; BETA-GLUCURONIDASE DEFICIENCY; ENZYME REPLACEMENT THERAPY; NEURAL STEM-CELLS; MURINE MODEL; BRAIN-LESIONS; FLUID; IMPROVES; MOUSE AB Lysosomal storage diseases (LSDs) represent a significant portion of inborn metabolic disorders. More than 60% of LSDs have CNS involvement. LSD therapies for systemic diseases have been developed, but efficacy does not extend to the CNS. In this study, we tested whether adeno-associated virus type 4 (AAV4) vectors could mediate global functional and pathological improvements in a murine model of mucopolysaccharidosis type VII (MPS VII) caused by beta-glucuronidase deficiency. Recombinant AAV4 vectors encoding beta-glucuronidase were injected unilaterally into the lateral ventricle of MPS VII mice with established disease. Transduced ependyma expressed high levels of recombinant enzyme, with secreted enzyme penetrating cerebral and cerebellar structures, as well as the brainstem. Immunohistochemical studies revealed close association of recombinant enzyme and brain microvasculature, indicating that beta-glucuronidase reached brain parenchyma via the perivascular spaces lining blood vessels. Aversive associative learning was tested by context fear conditioning. Compared with age-matched heterozygous controls, affected mice showed impaired conditioned fear response and context discrimination. This behavioral deficit was reversed 6 weeks after gene transfer in AAV4 beta-glucuronidase-treated MPS VII mice. Our data show that ependymal cells can serve as a source of enzyme secretion into the surrounding brain parenchyma and CSF. Secreted enzymes subsequently spread via various routes to reach structures throughout the brain and mediated pathological and functional disease correction. Together, our proof-of-principal experiments suggest a unique and efficient manner for treating the global CNS deficits in LSD patients. C1 Univ Iowa, Program Gene Therapy, Dept Internal Med, Iowa City, IA 52242 USA. Univ Iowa, Program Gene Therapy, Dept Neurol, Iowa City, IA 52242 USA. Univ Iowa, Program Gene Therapy, Dept Physiol & Biophys, Iowa City, IA 52242 USA. Univ Iowa, Program Gene Therapy, Dept Psychiat, Iowa City, IA 52242 USA. NIH, Bethesda, MD 20892 USA. RP Davidson, BL (reprint author), Univ Iowa, Program Gene Therapy, Dept Internal Med, 200 Eckstein Med Res Bldg, Iowa City, IA 52242 USA. EM beverly-davidson@uiowa.edu FU NICHD NIH HHS [HD 33531] NR 38 TC 68 Z9 69 U1 0 U2 2 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD OCT 12 PY 2005 VL 25 IS 41 BP 9321 EP 9327 DI 10.1523/JNEUROSCI.2936-05.2005 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 973TU UT WOS:000232546300001 PM 16221840 ER PT J AU Stefan, K Cohen, LG Duque, J Mazzocchio, R Celnik, P Sawaki, L Ungerleider, L Classen, J AF Stefan, K Cohen, LG Duque, J Mazzocchio, R Celnik, P Sawaki, L Ungerleider, L Classen, J TI Formation of a motor memory by action observation SO JOURNAL OF NEUROSCIENCE LA English DT Article DE action observation; motor cortex; human; plasticity; mirror neuron system; memory ID TRANSCRANIAL MAGNETIC STIMULATION; VENTRAL PREMOTOR CORTEX; HAND ACTIONS; MOVEMENT OBSERVATION; FACILITATION; MODULATION; PLASTICITY; EXCITABILITY; ACQUISITION; ACTIVATION AB Mirror neurons discharge with both action observation and action execution. It has been proposed that the mirror neuron system is instrumental in motor learning. The human primary motor cortex (M1) displays mirror activity in response to movement observation, is capable of forming motor memories, and is involved in motor learning. However, it is not known whether movement observation can lead directly to the formation of motor memories in the M1, which is considered a likely physiological step in motor learning. Here, we used transcranial magnetic stimulation (TMS) to show that observation of another individual performing simple repetitive thumb movements gives rise to a kinematically specific memory trace of the observed motions in M1. An extended period of observation of thumb movements that were oriented oppositely to the previously determined habitual directional bias increased the probability of TMS-evoked thumb movements to fall within the observed direction. Furthermore, the acceleration of TMS-evoked thumb movements along the principal movement axis and the balance of excitability of muscle representations active in the observed movements were altered in favor of the observed movement direction. These findings support a role for the mirror neuron system in memory formation and possibly human motor learning. C1 Univ Wurzburg, Dept Neurol, Human Cort Physiol & Motor Control Lab, D-97080 Wurzburg, Germany. NINDS, Human Cort Physiol Sect, NIH, Bethesda, MD 20892 USA. NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. RP Cohen, LG (reprint author), Univ Wurzburg, Dept Neurol, Human Cort Physiol & Motor Control Lab, Josef Schneider Str 12, D-97080 Wurzburg, Germany. EM cohenl@ninds.nih.gov; Classen_J@klinik.uni-wuerzburg.de RI Mazzocchio, Riccardo/H-4223-2012 OI Mazzocchio, Riccardo/0000-0002-0628-2868 FU Intramural NIH HHS NR 60 TC 183 Z9 196 U1 3 U2 24 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD OCT 12 PY 2005 VL 25 IS 41 BP 9339 EP 9346 DI 10.1523/JNEUROSCI.2282-05.2005 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 973TU UT WOS:000232546300003 PM 16221842 ER PT J AU Kwon, OB Longart, M Vullhorst, D Hoffman, DA Buonanno, A AF Kwon, OB Longart, M Vullhorst, D Hoffman, DA Buonanno, A TI Neuregulin-1 reverses long-term potentiation at CA1 hippocampal synapses SO JOURNAL OF NEUROSCIENCE LA English DT Article DE neuregulin; depotentiation; ErbB receptor; LTP; LTD; schizophrenia; superecliptic GFP ID NMDA RECEPTORS; AMPA RECEPTORS; PREFRONTAL CORTEX; HOMOSYNAPTIC LTD; NERVOUS-SYSTEM; SCHIZOPHRENIA; EXPRESSION; ACTIVATION; NEURONS; DEPOTENTIATION AB Neuregulin-1 (NRG-1) has been identified genetically as a schizophrenia susceptibility gene, but its function in the adult brain is unknown. Here, we show that NRG-1 beta does not affect basal synaptic transmission but reverses long-term potentiation (LTP) at hippocampal Schaffer collateral -> CA1 synapses in an activity- and time-dependent manner. Depotentiation by NRG-1 beta is blocked by two structurally distinct and selective ErbB receptor tyrosine kinase inhibitors. Moreover, ErbB receptor inhibition increases LTP at potentiated synapses and blocks LTP reversal by theta-pulse stimuli. NRG-1 beta selectively reduces AMPA, not NMDA, receptor EPSCs and has no effect on paired-pulse facilitation ratios. Live imaging of hippocampal neurons transfected with receptors fused to superecliptic green fluorescent protein, as well as quantitative analysis of native receptors, show that NRG-1 beta stimulates the internalization of surface glutamate receptor 1-containing AMPA receptors. This novel regulation of LTP by NRG-1 has important implications for the modulation of synaptic homeostasis and schizophrenia. C1 NICHHD, NIH, Sect Mol Neurobiol, Bethesda, MD 20892 USA. NICHHD, NIH, Unit Neurophysiol & Biophys, Bethesda, MD 20892 USA. RP Buonanno, A (reprint author), NICHHD, NIH, Sect Mol Neurobiol, Bldg 35,Room 2C-1000, Bethesda, MD 20892 USA. EM buonanno@helix.nih.gov RI Hoffman, Dax/E-5155-2011 OI Hoffman, Dax/0000-0001-6999-2157 FU Intramural NIH HHS [Z99 HD999999] NR 38 TC 114 Z9 118 U1 0 U2 1 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD OCT 12 PY 2005 VL 25 IS 41 BP 9378 EP 9383 DI 10.1523/JNEUROSCI.210-05.2005 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 973TU UT WOS:000232546300007 PM 16221846 ER PT J AU Thompson, KG Biscoe, KL Sato, TR AF Thompson, KG Biscoe, KL Sato, TR TI Neuronal basis of covert spatial attention in the frontal eye field SO JOURNAL OF NEUROSCIENCE LA English DT Article DE vision; saccade; attention; monkey; physiology; premotor ID SACCADE TARGET SELECTION; MACAQUE AREA V4; VISUAL-SEARCH; SUPERIOR COLLICULUS; STIMULUS; CORTEX; MOVEMENTS; SHIFTS; MICROSTIMULATION; DISSOCIATION AB The influential "premotor theory of attention" proposes that developing oculomotor commands mediate covert visual spatial attention. A likely source of this attentional bias is the frontal eye field (FEF), an area of the frontal cortex involved in converting visual information into saccade commands. We investigated the link between FEF activity and covert spatial attention by recording from FEF visual and saccade-related neurons in monkeys performing covert visual search tasks without eye movements. Here we show that the source of attention signals in the FEF is enhanced activity of visually responsive neurons. At the time attention is allocated to the visual search target, nonvisually responsive saccade-related movement neurons are inhibited. Therefore, in the FEF, spatial attention signals are independent of explicit saccade command signals. We propose that spatially selective activity in FEF visually responsive neurons corresponds to the mental spotlight of attention via modulation of ongoing visual processing. C1 NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. RP Thompson, KG (reprint author), NEI, Sensorimotor Res Lab, NIH, Bldg 49,Room 2A50, Bethesda, MD 20892 USA. EM kgt@lsr.nei.nih.gov FU Intramural NIH HHS [Z01 EY000389-04] NR 63 TC 142 Z9 144 U1 1 U2 10 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD OCT 12 PY 2005 VL 25 IS 41 BP 9479 EP 9487 DI 10.1523/JNEUROSCI.0741-05.2005 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 973TU UT WOS:000232546300019 PM 16221858 ER PT J AU Smith, DL Waller, LA Russell, CA Childs, JE Real, LA AF Smith, DL Waller, LA Russell, CA Childs, JE Real, LA TI Assessing the role of long-distance translocation and spatial heterogeneity in the raccoon rabies epidemic in Connecticut SO PREVENTIVE VETERINARY MEDICINE LA English DT Article; Proceedings Paper CT GISVET 2004 Conference CY 2004 CL Univ Guelph, Guelph, CANADA HO Univ Guelph DE rabies; spatial spread; spatial heterogeneity; long-distance dispersal ID UNITED-STATES; PREDICTION; INFECTION; DYNAMICS AB Spatial heterogeneity and long-distance translocation (LDT) play important roles in the spatiotemporal dynamics and management of emerging infectious diseases and invasive species. We assessed the influence of LDT events on the invasive spread of raccoon rabies through Connecticut. We identified several putative LDT events, and developed a network-model to evaluate whether they became new foci for epidemic spread. LDT was fairly common, but many of the LDTs were isolated events that did not spread. Two putative LDT events did appear to become nascent foci that affected the epidemic in surrounding townships. In evaluating the role of LDT, we simultaneously revisited the problem of spatial heterogeneity. The spread of raccoon rabies is associated with forest cover-rabies moves up to three-times slower through the most heavily forested townships compared with those with less forestation. Forestation also modified the effect of rivers. In the best overall model, rabies did not cross the river separating townships that were heavily forested, and the spread slowed substantially between townships that were lightly forested. Our results suggest that spatial heterogeneity can be used to enhance the effects of rabies control by focusing vaccine bait distribution along rivers in lightly forested areas. LDT events are a concern, but this analysis suggests that at a local scale they can be isolated and managed. Published by Elsevier B.V. C1 Fogarty Int Ctr, Bethesda, MD 20892 USA. Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. Univ Cambridge, Dept Zool, Cambridge CB2 3EJ, England. Emory Univ, Dept Biol, Atlanta, GA 30322 USA. RP Smith, DL (reprint author), Fogarty Int Ctr, Room 309 Bldg 16,16 Ctr Dr, Bethesda, MD 20892 USA. EM smitdave@helix.nih.gov RI Russell, Colin/B-2226-2008; Childs, James/B-4002-2012; Smith, David/L-8850-2013 OI Smith, David/0000-0003-4367-3849 FU NIAID NIH HHS [AI047498] NR 20 TC 30 Z9 31 U1 1 U2 14 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-5877 J9 PREV VET MED JI Prev. Vet. Med. PD OCT 12 PY 2005 VL 71 IS 3-4 BP 225 EP 240 DI 10.1016/j.prevetmed.2005.07.009 PG 16 WC Veterinary Sciences SC Veterinary Sciences GA 982SK UT WOS:000233181700008 PM 16153724 ER PT J AU Arora, K Beard, WA Wilson, SH Schlick, T AF Arora, K Beard, WA Wilson, SH Schlick, T TI Mismatch-induced conformational distortions in polymerase support an induced-fit mechanism for fidelity SO BIOCHEMISTRY LA English DT Article ID DNA-REPLICATION FIDELITY; BASE EXCISION-REPAIR; STRUCTURAL INSIGHTS; MOLECULAR-DYNAMICS; KINETIC MECHANISM; ACTIVE-SITE; SUBSTRATE-SPECIFICITY; MINOR-GROOVE; I KLENOW; BETA AB Molecular dynamics simulations of DNA polymerase (pol) beta complexed with different incorrect incoming nucleotides (G center dot G, G center dot T, and T center dot T template base-incoming nucleotide combinations) at the template-primer terminus are analyzed to delineate structure-function relationships for aberrant base pairs in a polymerase active site. Comparisons, made to pol beta structure and motions in the presence of a correct base pair, are designed to gain atomically detailed insights into the process of nucleotide selection and discrimination. In the presence of an incorrect incoming nucleotide, alpha-helix N of the thumb subdomain believed to be required for pol beta's catalytic cycling moves toward the open conformation rather than the closed conformation as observed for the correct base pair (G center dot C) before the chemical reaction. Correspondingly, active-site residues in the microenvironment of the incoming base are in intermediate conformations for non-Watson-Crick pairs. The incorrect incoming nucleotide and the corresponding template residue assume distorted conformations and do not form Watson-Crick bonds. Furthermore, the coordination number and the arrangement of ligands observed around the catalytic and nucleotide binding magnesium ions are mismatch specific. Significantly, the crucial nucleotidyl transferase reaction distance (P-alpha-O3') for the mismatches between the incoming nucleotide and the primer terminus is not ideally compatible with the chemical reaction of primer extension that follows these conformational changes. Moreover, the extent of active-site distortion can be related to experimentally determined rates of nucleotide misincorporation and to the overall energy barrier associated with polymerase activity. Together, our studies provide structure-function insights into the DNA polymerase-induced constraints (i.e., alpha-helix N conformation, DNA base pair bonding, conformation of protein residues in the vicinity of dNTP, and magnesium ions coordination) during nucleotide discrimination and pol beta-nucleotide interactions specific to each mispair and how they may regulate fidelity. They also lend further support to our recent hypothesis that additional conformational energy barriers are involved following nucleotide binding but prior to the chemical reaction. C1 NYU, Dept Chem, New York, NY 10012 USA. NYU, Courant Inst Math Sci, New York, NY 10012 USA. Natl Inst Environm Hlth Sci, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Schlick, T (reprint author), NYU, Dept Chem, 251 Mercer St, New York, NY 10012 USA. EM schlick@nyu.edu OI arora, karunesh/0000-0003-3726-5304 FU Intramural NIH HHS; NIEHS NIH HHS [R01 ES012692]; NIGMS NIH HHS [R01 GM55164] NR 68 TC 49 Z9 50 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD OCT 11 PY 2005 VL 44 IS 40 BP 13328 EP 13341 DI 10.1021/bi0507682 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 972OM UT WOS:000232463100011 PM 16201758 ER PT J AU Bielekova, B Kadom, N Fisher, E Jeffries, N Ohayon, J Richert, N Howard, T Bash, CN Frank, JA Stone, L Martin, R Cutter, G McFarland, HF AF Bielekova, B Kadom, N Fisher, E Jeffries, N Ohayon, J Richert, N Howard, T Bash, CN Frank, JA Stone, L Martin, R Cutter, G McFarland, HF TI MRI as a marker for disease heterogeneity in multiple sclerosis SO NEUROLOGY LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; FUNCTIONAL COMPOSITE; DIAGNOSTIC-CRITERIA; OUTCOME MEASURE; RELAPSING MS; AXONAL LOSS; LESIONS; DISABILITY; DEMYELINATION; PROGRESSION AB Background: Whereas recent data from imaging studies challenge the prevailing notion that multiple sclerosis (MS) is purely an inflammatory disease, pathologic studies suggest differences in the disease processes between individual patients with MS. The ability to dissect the pathophysiologic disease heterogeneity, if it indeed exists, by methodologies that can be applied in vivo is important both for the development of new therapeutics and for the ability to identify the optimal therapy for an individual patient. Objective: To design a stratification algorithm for patients with MS based on accepted MRI measurements reflective of inflammation and axonal damage/ tissue loss and to assess if such MS subgroups retain their intergroup differences long term. Methods: Mathematical modeling was used to select three discriminatory MRI measures for clinical outcome based on the cross-sectional analysis of 71 patients with untreated MS and tested general applicability of the stratification scheme on the independent longitudinal cohort of 71 MS patients. Results: By consecutive employment of MRI measures reflective of inflammation and tissue loss, the authors were able to separate MS patients into four clinically meaningful subgroups. The analysis of the longitudinal confirmatory cohort demonstrated persistence of the intergroup differences in selected MRI measures for 8 years. Conclusions: The inflammatory activity and destructiveness of the multiple sclerosis process are to some degree independent of each other, and the successive evaluation of both of these variables can strengthen prediction of clinical outcome in individual patients. C1 NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. NINDS, Stat Branch, NIH, Bethesda, MD 20892 USA. NIH, Expt Neuroimaging Sect, Ctr Clin, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. Cleveland Clin Fdn, Dept Neurol, Mellen Ctr Multiple Sclerosis Treatment & Res, Cleveland, OH 44195 USA. Cleveland Clin Fdn, Dept Biomed Engn, Cleveland, OH 44195 USA. Univ Alabama, Dept Biostat, Birmingham, AL 35294 USA. RP Bielekova, B (reprint author), NINDS, Neuroimmunol Branch, NIH, 10 Ctr Dr,Bldg 10,Room 5B-16,MSC 1400, Bethesda, MD 20892 USA. EM bielekob@ninds.nih.gov FU CSR NIH HHS [RG3223A2/1]; Intramural NIH HHS NR 33 TC 44 Z9 45 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD OCT 11 PY 2005 VL 65 IS 7 BP 1071 EP 1076 DI 10.1212/01.wnl.0000178984.30534.f9 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 972RF UT WOS:000232470200019 PM 16217061 ER PT J AU Malathi, K Paranjape, JM Bulanova, E Shim, M Guenther-Johnson, JM Faber, PW Eling, TE Williams, BRG Silverman, RH AF Malathi, K Paranjape, JM Bulanova, E Shim, M Guenther-Johnson, JM Faber, PW Eling, TE Williams, BRG Silverman, RH TI A transcriptional signaling pathway in the IFN system mediated by 2 '-5 '-oligoadenylate activation of RNase L SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE prostate; macrophage inhibotory cytokine 1; HPC1; RNASEL ID PROSTATE-CANCER CELLS; RIBOTOXIC STRESS-RESPONSE; INTERFERON-TREATED CELLS; TGF-BETA SUPERFAMILY; 2-5A-DEPENDENT RNASE; GERMLINE MUTATIONS; SEQUENCE VARIANTS; VIRUS-INFECTION; RIBONUCLEASE-L; RIBOSOMAL-RNA AB Virus replication in higher vertebrates is restrained by IFNs that cause cells to transcribe genes encoding antiviral proteins, such as 2'-5' oligoadenylate synthetases. 2'-5' oligoadenylate synthetase is stimulated by dsRNA to produce 5'-phosphorylated, 2'-5'-linked oligoadenylates (2-5A), whose function is to activate RNase L. Although RNase L is required for a complete IFN antiviral response and mutations in the RNase L gene (RNASEL or HPC1) increase prostate cancer rates, it is unknown how 2-5A affects these biological endpoints through its receptor, RNase L. Presently, we show that 2-5A activation of RNase L produces a remarkable stimulation of transcription (>= 20-fold) for genes that suppress virus replication and prostate cancer. Unexpectedly, exposure of DU145 prostate cancer cells to physiologic levels of 2-5A (0.1 mu m) induced approximately twice as many RNA species as it downregulated. Among the 2-5A-induced genes are several IFN-stimulated genes, including IFN-inducible transcript 1 /P56, IFN-inducible transcript 2/P54, IL-8, and IFNI-stimulated gene 15. 2-5A also potently elevated RNA for macrophage inhibitory cytokine-1/nonsteroidal antiinflammatory drug-activated gene-1, a TGF-beta superfamily member implicated as an apoptotic suppressor of prostate cancer. Transcriptional signaling to the macrophage inhibitory cytokine-1/nonsteroidal antiinflammatory drug-activated gene-1 promoter by 2-5A was deficient in HeLa cells expressing a nuclease-dead mutant of RNase L and was dependent on the mitogenactivated protein kinases c-Jun N-terminal kinase and extracellular signal-regulated kinase, both of which were activated in response to 2-5A treatments. Because 2-5A and RNase L participate in defenses against viral infections and prostate cancer, our findings have implications for basic cellular mechanisms that control major pathogenic processes. C1 Cleveland Clin Fdn, Lerner Res Inst, Dept Canc Biol, Cleveland, OH 44195 USA. NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Silverman, RH (reprint author), Cleveland Clin Fdn, Lerner Res Inst, Dept Canc Biol, 9500 Euclid Ave, Cleveland, OH 44195 USA. EM silverr@ccf.org RI Williams, Bryan/A-5021-2009 OI Williams, Bryan/0000-0002-4969-1151 FU NCI NIH HHS [P01 CA62220, P01 CA062220, R01 CA044059, R01 CA44059]; NIAID NIH HHS [R15 AI089518, R15 AI089518-01] NR 42 TC 71 Z9 79 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 11 PY 2005 VL 102 IS 41 BP 14533 EP 14538 DI 10.1073/pnas.0507551102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 974PJ UT WOS:000232603600013 PM 16203993 ER PT J AU Zhou, TQ Hamer, DH Hendrickson, WA Sattentau, QJ Kwong, PD AF Zhou, TQ Hamer, DH Hendrickson, WA Sattentau, QJ Kwong, PD TI Interfacial metal and antibody recognition SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE antibody Q425; CD4; crystal structure; HIV ID TYROSINE SULFATION; BINDING; HIV-1; GP120; METALLOANTIBODIES; NEUTRALIZATION; CHEMISTRY; RECEPTOR; COMPLEX; ANTIGEN AB The unique ligation properties of metal ions are widely exploited by proteins, with approximately one-third of all proteins estimated to be metalloproteins. Although antibodies use various mechanisms for recognition, to our knowledge, none has ever been characterized that uses an interfacial metal. We previously described a family of CD4-reactive antibodies, the archetype being Q425. CD4:Q425 engagement does not interfere with CD4:HIV-1 gp120 envelope glycoprotein binding, but it blocks subsequent steps required for viral entry. Here, we use surface-plasmon resonance to show that Q425 requires calcium for recognition of CD4. Specifically, Q425 binding of calcium resulted in a 55,000-fold enhancement in affinity for CD4. X-ray crystallographic analyses of Q425 in the presence of Ca2+, Ba2+, or EDTA revealed an exposed metal-binding site, partially coordinated by five atoms contributed from four antibody complementarity-determining regions. The results suggest that Q425 recognition of CD4 involves direct ligation of antigen by the Q425-held calcium, with calcium binding each ligating atom of CD4 with approximate to 1.5 kcal/mol of binding energy. This energetic contribution, which is greater than that from a typical protein atom, demonstrates how interfacial metal ligation can play a unique role in antigen recognition. C1 NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. Columbia Univ, Dept Biochem & Mol Biophys, New York, NY 10032 USA. Columbia Univ, Howard Hughes Med Inst, New York, NY 10032 USA. Univ Oxford, Sir William Dunn Sch Pathol, Oxford OX1 3RE, England. RP Hendrickson, WA (reprint author), NIAID, Vaccine Res Ctr, NIH, 40 Convent Dr,Bldg 40,Room 4508, Bethesda, MD 20892 USA. EM wayne@convex.hhmi.columbia.edu; pdkwong@nih.gov RI Zhou, Tongqing/A-6880-2010 OI Zhou, Tongqing/0000-0002-3935-4637 FU NIAID NIH HHS [AI40895, R01 AI040895] NR 35 TC 16 Z9 17 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 11 PY 2005 VL 102 IS 41 BP 14575 EP 14580 DI 10.1073/pnas.0507267102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 974PJ UT WOS:000232603600020 PM 16195378 ER PT J AU Odenwald, WF Rasband, W Kuzin, A Brody, T AF Odenwald, WF Rasband, W Kuzin, A Brody, T TI EVOPRINTER, a multigenomic comparative tool for rapid identification of functionally important DNA SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE comparative genomics; evolution; gene structure and function ID DROSOPHILA KRUPPEL PROTEIN; DEVELOPING NERVOUS-SYSTEM; ACHAETE-SCUTE HOMOLOG-1; FACTOR-BINDING SITES; TRANSCRIPTION FACTOR; NEUROENDOCRINE DIFFERENTIATION; REGULATORY ELEMENTS; TEMPORAL IDENTITY; EXPRESSION; GENE AB Here, we describe a multigenomic DNA sequence-analysis tool, EVOPRINTER, that facilitates the rapid identification of evolutionary conserved sequences within the context of a single species. The EVOPRINTER output identifies multispecies-conserved DNA sequences as they exist in a reference DNA. This identification is accomplished by superimposing multiple reference DNA vs. test-genome pairwise BLAT (BLAST-like alignment tool) readouts of the reference DNA to identify conserved nucleotides that are shared by all orthologous DNAs. EVOPRINTER analysis of well characterized genes reveals that most, if not all, of the conserved sequences are essential for gene function. For example, analysis of orthologous genes that are shared by many vertebrates identifies conserved DNA in both protein-encoding sequences and noncoding cis-regulatory regions, including enhancers and mRNA microRNA binding sites. In Drosophila, the combined mutational histories of five or more species affords near-base pair resolution of conserved transcription factor DNA-binding sites, and essential amino acids are revealed by the nucleotide flexibility of their codon-wobble position(s). Conserved small peptide-encoding genes, which had been undetected by conventional gene-prediction algorithms, are identified by the codon-wobble signatures of invariant amino acids. Also, EVOPRINTER allows one to assess the degree of evolutionary divergence between orthologous DNAs by highlighting differences between a selected species and the other test species. C1 NINDS, Neural Cell Fate Determinants Sect, NIH, Bethesda, MD 20892 USA. NIMH, Off Sci Director, Intramural Res Program, NIH, Bethesda, MD 20892 USA. RP Odenwald, WF (reprint author), NINDS, Neural Cell Fate Determinants Sect, NIH, Bethesda, MD 20892 USA. EM ward@codon.nih.gov; brodyt@ninds.nih.gov FU Intramural NIH HHS NR 46 TC 46 Z9 47 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 11 PY 2005 VL 102 IS 41 BP 14700 EP 14705 DI 10.1073/pnas.0506915102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 974PJ UT WOS:000232603600041 PM 16203978 ER PT J AU Cesari, M Kritchevsky, SB Nicklas, BJ Penninx, BWHJ Holvoet, P Koh-Banerjee, P Cummings, SR Harris, TB Newman, AB Pahor, M AF Cesari, M Kritchevsky, SB Nicklas, BJ Penninx, BWHJ Holvoet, P Koh-Banerjee, P Cummings, SR Harris, TB Newman, AB Pahor, M TI Lipoprotein peroxidation and mobility limitation - Results from the health, aging, and body composition study SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID LOW-DENSITY-LIPOPROTEIN; NECROSIS-FACTOR-ALPHA; CIRCULATING OXIDIZED LDL; LIPID-PEROXIDATION; PLATELET ACTIVATION; OLDER-ADULTS; VITAMIN-E; PHYSICAL-ACTIVITY; SKELETAL-MUSCLE; PLASMA IL-6 AB Background: Oxidative damage plays an important role in leading to major health-related events. The aim of this study was to assess the predictive value of a lipoprotein peroxidation marker, oxidized low-density lipoprotein (oxLDL) for incident mobility limitation (ML). Methods: Data are from 2985 well-functioning elders enrolled in the Health ABC study (median follow-up, 4.1 years). All oxLDL levels were measured at the baseline assessment. The oxLDL/LDL cholesterol (LDL-C) ratio (log value) was used as a measure of lipoprotein peroxidation. Mobility limitation was defined by 2 consecutive semiannual reports of any difficulty either walking 1/4 mile or climbing up 10 steps without resting. Severe ML was defined by 2 consecutive reports of great difficulty or inability to do the same tasks. Cox proportional hazards models were performed to assess hazard ratios (HRs) and 95% confidence intervals (CIs). Results: The mean (SD) age of the sample was 74.2 (2.9) years. After adjustment for potential confounders (Sociodemographic factors, smoking, physical activity, body mass index, clinical conditions, biological markers, and medications), the relationship between the oxLDL/LDL-C ratio and disability events was statistically significant (per log-unit difference in the oxLDL/LDL-C ratio) (for ML: HR, 1.22; 95% CI, 1.06-1.41; for severe ML: HR, 1.43; 95% CI, 1.15-1.79). Consistent results were found when interleukin 6 level was included as a covariate in the adjusted models (ML HR, 1.13; 95% CI, 0.98-1.31; severe ML: HR, 1.31; 95% CI, 1.05-1.64). No significant sex, race, interleukin 6 level, or clinical conditions interaction was found with the oxLDL/LDL-C ratio and mobility disability. Conclusions: Lipoprotein peroxidation predicts the onset of ML in older persons. The oxLDL predictive value for ML is partly explained by interleukin 6 levels. C1 Univ Florida, Inst Aging, Coll Med, Dept Aging & Geriatr Res, Gainesville, FL 32608 USA. Wake Forest Univ, Sch Med, Stricht Ctr Aging & Rehab, Winston Salem, NC USA. Vrije Univ Amsterdam, Dept Psychiat, Amsterdam, Netherlands. Katholieke Univ Leuven, Ctr Expt Surg & Anesthesiol, Louvain, Belgium. Univ Tennessee, Dept Prevent Med, Memphis, TN USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Natl Inst Aging, NIH, Bethesda, MD USA. Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. RP Cesari, M (reprint author), Univ Florida, Inst Aging, Coll Med, Dept Aging & Geriatr Res, 1329 SW 16th St,Room 5273, Gainesville, FL 32608 USA. EM mcesari@aging.ufl.edu RI Cesari, Matteo/A-4649-2008; Newman, Anne/C-6408-2013 OI Cesari, Matteo/0000-0002-0348-3664; Newman, Anne/0000-0002-0106-1150 FU NIA NIH HHS [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, P30-AG-021332-02] NR 52 TC 22 Z9 23 U1 1 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD OCT 10 PY 2005 VL 165 IS 18 BP 2148 EP 2154 DI 10.1001/archinte.165.18.2148 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 974FN UT WOS:000232576800014 PM 16217006 ER PT J AU Sarkar, S Maceyka, M Hait, NC Paugh, SW Sankala, H Milstien, S Spiegel, S AF Sarkar, S Maceyka, M Hait, NC Paugh, SW Sankala, H Milstien, S Spiegel, S TI Sphingosine kinase 1 is required for migration, proliferation and survival of MCF-7 human breast cancer cells SO FEBS LETTERS LA English DT Article DE sphingosine-1-phosphate; sphingosine kinase; epidermal growth factor; MCF-7; cell migration; apoptosis ID EPIDERMAL-GROWTH-FACTOR; FUNCTIONAL-CHARACTERIZATION; MOLECULAR-CLONING; INDUCED APOPTOSIS; SPHINGOSINE-1-PHOSPHATE; RECEPTORS; MOTILITY; PROTEIN; 1-PHOSPHATE; ACTIVATION AB Sphingosine-1 -phosphate (S1P) is a potent lysolipid involved in a variety of biological responses important for cancer progression. Therefore, we investigated the role of sphingosine kinase type 1 (SphK1), the enzyme that makes SIP, in the motility, growth, and chemoresistance of MCF-7 breast cancer cells. Epidermal growth factor (EGF), an important growth factor for breast cancer progression, activated and translocated SphK1 to plasma membrane. SphK1 was required for EGF-directed motility. Downregulation of SphK1 in MCF-7 cells reduced EGF- and serum-stimulated growth and enhanced sensitivity to doxorubicin, a potent chemotherapeutic agent. These results suggest that SphK1 may be critical for growth, metastasis and chemoresistance of human breast cancers. (c) 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. C1 Virginia Commonwealth Univ, Sch Med, Dept Biochem, Richmond, VA 23298 USA. Massey Canc Ctr, Richmond, VA 23298 USA. NIMH, Lab Cellular & Mol Regulat, NIH, Bethesda, MD 20892 USA. RP Spiegel, S (reprint author), Virginia Commonwealth Univ, Sch Med, Dept Biochem, 1101 E Marshall St, Richmond, VA 23298 USA. EM sspiegel@vcu.edu RI Paugh, Steven/A-7739-2008; Maceyka, Michael/B-9277-2008 OI Paugh, Steven/0000-0001-5697-9228; FU NCI NIH HHS [P30 CA16059, R01CA61774] NR 27 TC 111 Z9 121 U1 0 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD OCT 10 PY 2005 VL 579 IS 24 BP 5313 EP 5317 DI 10.1016/j.febslet.2005.08.055 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 973LH UT WOS:000232523600010 PM 16194537 ER PT J AU Bilke, S Chen, QR Westerman, F Schwab, M Catchpoole, D Khan, J AF Bilke, S Chen, QR Westerman, F Schwab, M Catchpoole, D Khan, J TI Inferring a tumor progression model for neuroblastoma from genomic data SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID HYBRIDIZATION CGH ANALYSIS; GENE-EXPRESSION; MYCN-AMPLIFICATION; COLORECTAL-CANCER; MICROARRAY DATA; TREE MODELS; DNA; PLOIDY; PREDISPOSITION; MUTATIONS AB Purpose The knowledge of the key genomic events that are causal to cancer development and progression not only is invaluable for our understanding of cancer biology but also may have a direct clinical impact. The task of deciphering a model of tumor progression by requiring that it explains (or at least does not contradict) known clinical and molecular evidence can be very demanding, particularly for cancers with complex patterns of clinical and molecular evidence. Materials and Methods We formalize the process of model inference and show how a progression model for neuroblastoma (NB) can be inferred from genomic data. The core idea of our method is to translate the model of clonal cancer evolution to mathematical testable rules of inheritance. Seventy-eight NB samples in stages 1, 4S, and 4 were analyzed with array-based comparative genomic hybridization. Results The pattern of recurrent genomic alterations in NB is strongly stage dependent and it is possible to identify traces of tumor progression in this type of data. Conclusion A tumor progression model for neuroblastoma is inferred, which is in agreement with clinical evidence, explains part of the heterogeneity of the clinical behavior observed for NB, and is compatible with existing empirical models of NB progression. C1 NCI, Ctr Adv Technol, Bethesda, MD 20892 USA. NCI, Oncogenom Sect, Pediat Oncol Branch, Ctr Adv Technol, Gaithersburg, MD USA. German Canc Res Ctr, Dept Tumor Genet, D-6900 Heidelberg, Germany. Childrens Hosp, Tumor Bank, Westmead, NSW, Australia. RP Khan, J (reprint author), NCI, Ctr Adv Technol, Room 134E,8717 Grovemt Cir, Bethesda, MD 20892 USA. EM khanjav@mail.nih.gov RI Khan, Javed/P-9157-2014 OI Khan, Javed/0000-0002-5858-0488 FU Intramural NIH HHS NR 45 TC 28 Z9 30 U1 0 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD OCT 10 PY 2005 VL 23 IS 29 BP 7322 EP 7331 DI 10.1200/JCO.2005.03.2821 PG 10 WC Oncology SC Oncology GA 973TT UT WOS:000232546200009 PM 16145061 ER PT J AU Simon, R AF Simon, R TI Roadmap for developing and validating therapeutically relevant genomic classifiers SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID METASTATIC BREAST-CANCER; GENE-EXPRESSION DATA; CLASS PREDICTION; LUNG-CANCER; CLASSIFICATION; CHEMOTHERAPY; MUTATIONS; GEFITINIB; DISCOVERY; SURVIVAL AB Oncologists need improved tools for selecting treatments for individual patients. The development of therapeutically relevant prognostic markers has traditionally been slowed by poor study design, inconsistent findings, and lack of proper validation studies. Microarray expression profiling provides an exciting new technology for relating tumor gene expression to patient outcome, but it also provides increased challenges for translating initial research findings into robust diagnostics that benefit patients and physicians in therapeutic decision making. This article attempts to clarify some of the misconceptions about the development and validation of multigene expression signature classifiers and highlights the steps needed to move genomic signatures into clinical application as therapeutically relevant and robust diagnostics. C1 NCI, Biometr Res Branch, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. RP Simon, R (reprint author), NCI, Biometr Res Branch, Div Canc Treatment & Diag, NIH, 9000 Rockville Pike,MSC 7434, Bethesda, MD 20892 USA. EM rsimon@nih.gov NR 29 TC 234 Z9 242 U1 0 U2 6 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD OCT 10 PY 2005 VL 23 IS 29 BP 7332 EP 7341 DI 10.1200/JCO.2005.02.8712 PG 10 WC Oncology SC Oncology GA 973TT UT WOS:000232546200010 PM 16145063 ER PT J AU Hlavaty, J Schittmayer, M Stracke, A Jandl, G Knapp, E Felber, BK Salmons, B Gunzburg, WH Renner, M AF Hlavaty, J Schittmayer, M Stracke, A Jandl, G Knapp, E Felber, BK Salmons, B Gunzburg, WH Renner, M TI Effect of posttranscriptional regulatory elements on transgene expression and virus production in the context of retrovirus vectors SO VIROLOGY LA English DT Article DE retrovirus vector; RNA transport element (RTE); CTE; WPRE; Hsp70 ID INTERNAL RIBOSOME ENTRY; CONSTITUTIVE TRANSPORT ELEMENT; MESSENGER-RNA TRANSLATION; LENTIVIRAL VECTORS; DUCTAL ADENOCARCINOMAS; 5'-UNTRANSLATED REGION; TYPE-1 EXPRESSION; DEPENDENT MANNER; GENE-EXPRESSION; GAG EXPRESSION AB Ineffective transgene expression in a sufficient amount of target cells is still a limitation in retroviral vector mediated gene therapy. Thus, we systematically evaluated four genetic modulators, (i) the woodchuck posttranscriptional regulatory element (WPRE), (ii) the mouse RNA transport element (RTE), (iii) the constitutive transport element (CTE) of the simian retrovirus type 1 (SRV-1), and (iv) the 5' untranslated region of the human heat shock protein 70 (Hsp70 5'UTR), all of them involved in the posttranscriptional control of mRNA nucleo/ cytoplasmatic transport, RNA stability, and translation efficiency, in an MLV-based retrovirus vector context. Insertion of the WPRE into the retrovirus vector resulted in enhancement of transgene expression (EGFP) both in transfected virus producing cells as well as in infected recipient cells irrespective of the location in the vector. The best effect was observed with two copies of the WPRE, 3' of the transgene and in the 3' untranslated region of the vector backbone. However, oligomerization of this element does not further increase transgene expression. Presence of the WPRE resulted also in an increase in virus production. Introduction of the CTE and/or RTE in the retroviral vector did not alter transgene expression and infectious particle production. Positive effects were observed only in vectors harboring the CTE and/or RTE in combination with the WPRE. The activity of the Hsp70 5'UTR as a translational enhancer was found to be negligible in the context of the retroviral vector. However, interference of the Hsp70 5'UTR strong secondary structure with the packaging sequence of the viral RNA was experimentally excluded as being the cause of this. These data suggest that only the WPRE is a suitable element for the improvement of transgene expression and oncoretroviral vector production. (c) 2005 Elsevier Inc. All rights reserved. C1 Austrianova Biotechnol GmbH, A-1210 Vienna, Austria. Univ Vet Med, Res Inst Virol & Biomed, A-1210 Vienna, Austria. Slovak Acad Sci, Canc Res Inst, SK-84102 Bratislava, Slovakia. Christian Doppler Lab Gene Therapeut Vector Dev, A-1210 Vienna, Austria. NCI, Human Retrovirus Pathogenesis Sect, Vaccine Branch, Frederick, MD 21702 USA. RP Salmons, B (reprint author), Austrianova Biotechnol GmbH, A-1210 Vienna, Austria. EM salmons@austrianova.com NR 50 TC 19 Z9 20 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD OCT 10 PY 2005 VL 341 IS 1 BP 1 EP 11 DI 10.1016/j.virol.2005.06.037 PG 11 WC Virology SC Virology GA 973BW UT WOS:000232498900001 PM 16054668 ER PT J AU Aldaz-Carroll, L Whitbeck, JC de Leon, MP Lou, H Pannell, LK Lebowitz, J Fogg, C White, CL Moss, B Cohen, GH Eisenberg, RJ AF Aldaz-Carroll, L Whitbeck, JC de Leon, MP Lou, H Pannell, LK Lebowitz, J Fogg, C White, CL Moss, B Cohen, GH Eisenberg, RJ TI Physical and immunological characterization of a recombinant secreted form of the membrane protein encoded by the vaccinia virus L1R gene SO VIROLOGY LA English DT Article DE vaccinia virus; L1R; disulfide; neutralizing; monoclonal; epitope; 2D5; 7D11; baculovirus; antibody ID EXTRACELLULAR ENVELOPED VIRUS; HERPESVIRUS ENTRY MEDIATOR; DISULFIDE BOND FORMATION; GLYCOPROTEIN-D; MONOCLONAL-ANTIBODIES; PENETRATION PROTEIN; SOLUBLE FORMS; INSECT CELLS; VACCINATION; EXPRESSION AB We reported that immunization with recombinant proteins derived from vaccinia virus (VV) particles could provide protection against infection. Here we describe the physical and antigenic properties of the L1R membrane protein. The recombinant protein (L1R(185t)) was secreted as a monomer and correct folding was suggested by the presence of three intramolecular disulfide bonds and binding to conformation-specific monoclonal antibodies (MAbs). Furthermore, anti-L1R(185t) rabbit antisera exhibited potent virus-neutralizing activity against the IMV form of VV. We raised six MAbs against L1R(185t). Three recognized linear epitopes (residues 118-128) and neutralized IMV infectivity. These MAbs blocked binding of each other to L1R(185t) but failed to block binding of two previously described neutralizing anti-L1R MAbs, 7D11 and 2D5. The latter two antibodies blocked each other in binding L1R(185t). Thus, two antigenic sites on L1R overlap functional domains and based on recent structural studies these are found in accessible regions of the IMV L1R protein. (c) 2005 Elsevier Inc. All rights reserved. C1 Univ Penn, Sch Dent Med, Dept Microbiol, Philadelphia, PA 19104 USA. Univ S Alabama, Inst Canc Res, Mobile, AL 36688 USA. NIH, Off Res Serv, Bethesda, MD 20892 USA. NIAID, NIH, Bethesda, MD 20892 USA. RP Aldaz-Carroll, L (reprint author), Univ Penn, Sch Dent Med, Dept Microbiol, 240 S 40th St, Philadelphia, PA 19104 USA. EM aldaz@biochem.dental.upenn.edu RI Aldaz-Carroll, Lydia/A-6180-2008 FU NIAID NIH HHS [R21-AI-53404] NR 33 TC 40 Z9 40 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 0042-6822 J9 VIROLOGY JI Virology PD OCT 10 PY 2005 VL 341 IS 1 BP 59 EP 71 DI 10.1016/j.virol.2005.07.006 PG 13 WC Virology SC Virology GA 973BW UT WOS:000232498900006 PM 16083934 ER PT J AU Zitserman, VY Berezhkovskii, AM Parsegian, VA Bezrukov, SM AF Zitserman, VY Berezhkovskii, AM Parsegian, VA Bezrukov, SM TI Nonideality of polymer solutions in the pore and concentration-dependent partitioning SO JOURNAL OF CHEMICAL PHYSICS LA English DT Letter C1 Russian Acad Sci, Inst High Temp, Thermophys Ctr, Moscow 127412, Russia. NIH, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA. NICHD, Lab Phys & Struct Phys, NIH, Bethesda, MD 20892 USA. RP Bezrukov, SM (reprint author), Russian Acad Sci, Inst High Temp, Thermophys Ctr, Izhorskaya 13-19, Moscow 127412, Russia. EM bezrukos@mail.nih.gov FU Intramural NIH HHS NR 12 TC 6 Z9 6 U1 0 U2 2 PU AMER INST PHYSICS PI MELVILLE PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1, MELVILLE, NY 11747-4501 USA SN 0021-9606 J9 J CHEM PHYS JI J. Chem. Phys. PD OCT 8 PY 2005 VL 123 IS 14 AR 146101 DI 10.1063/1.2052589 PG 2 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 973OH UT WOS:000232532000071 PM 16238435 ER PT J AU Childers, ML Su, F Przyborowska, AM Bishwokarma, B Park, G Brechbiel, MW Torti, SV Torti, FM Broker, G Alexander, JS Rogers, RD Ruhlandt-Senge, K Planalp, RP AF Childers, ML Su, F Przyborowska, AM Bishwokarma, B Park, G Brechbiel, MW Torti, SV Torti, FM Broker, G Alexander, JS Rogers, RD Ruhlandt-Senge, K Planalp, RP TI Pyridine-ring alkylation of cytotoxic r-1,c-3,c-5-tris[(2-pyridylmethyl)amino]cyclohexane chelators: Structural and electronic properties of the Mn-II, Fe-II, Ni-II, Cu-II and Zn-II complexes SO EUROPEAN JOURNAL OF INORGANIC CHEMISTRY LA English DT Article DE antitumor activity; tripodal ligands; ligand design; iron; zinc; copper ID EFFECTIVE IONIC-RADII; COPPER(II) COMPLEXES; NICKEL(II) ANALOGS; METAL-COMPLEXES; IRON COMPLEXES; N,N',N''-TRIS(2-PYRIDYLMETHYL)-CIS,CIS-1,3,5-TRIAMINOCYCLOHEXANE; CIS,CIS-1,3,5-TRIAMINOCYCLOHEXANE; PROLIFERATION; COORDINATION; LIGANDS AB Effects of pyridyl-ring alkylation on complexation of Mu(II), Fe-II, Ni-II, Cu-II and Zn-II by chelators based on r-1,c-3,c-5-triaminocyclohexane (tach) have been studied. The chelators studied are N,N',N ''-tris[(x-alkyl-2-pyridyl)methyl] derivatives of tach, where the ring substituents are 3-Me, 4-Me, 5Me, 6-Me or 6-MeO ("tach-x-Rpyr"). Dicationic complexes were synthesized for most combinations of the above five metals and five chelators, using ClO4-, NO3-, Cl-, or CF3SO3- as counterions. Their bonding, structure, and aqueous lability were analyzed by UV/Vis/NIR spectroscopy, magnetic moment determination, HPLC, and single-crystal X-ray crystallography. The striking features are seen in the 6-alkylated complexes, where steric repulsions between the 6-substituents at the threefold axis of the pseudo-octahedral coordination sphere result in a substantially weakened metal-ligand interaction. In the [M(tach-6-Rpyr)](2+) series of divalent Mn, Ni, Cu and Zn, effects of these repulsions include bond angle and length distortions, decrease of the coordination number to five, shifts of d-d electronic transitions to lower energies, and spin-free complexes of the bound metal ion. Aqueous lability studies by HPLC agree with the spectroscopic findings. The bonding properties of the other tach-x-Mepyr chelators (x = 3, 4, 5) closely resemble the unalkylated parent tachpyr in solution. Similarly in the X-ray studies, [Zn(tach-3-Mepyr)](2+) resembles [Zn(tachpyr)](2+). The cytotoxicities of the chelators toward human breast cancer cells (MCF7) at a fixed chelator concentration of 16 mu m show time-dependent induction of cell death in the order tach-3-Mepyr > approximate to tach-4-Mepyr > tach-5-Mepyr > tachpyr, whereas tach-6-Mepyr and tach-6-MeOpyr had no effect on the cells. The depressed cytotoxicities of the latter two are attributed to inability to bind Fe-II or Zn-II strongly. (c) Wiley-VCH Verlag GmbH & Co. C1 Kunsan Natl Univ, Sch Sci & Technol, Kusan 573701, Jeollabukdo, South Korea. Univ New Hampshire, Dept Chem, Durham, NH 03824 USA. NIH, Radiat Oncol Branch, Bethesda, MD 20892 USA. Wake Forest Univ Hlth Sci, Dept Biochem, Winston Salem, NC 27157 USA. Wake Forest Univ Hlth Sci, Dept Canc Biol, Winston Salem, NC 27157 USA. Wake Forest Univ Hlth Sci, Ctr Comprehens Canc, Winston Salem, NC 27157 USA. Univ Alabama, Dept Chem, Tuscaloosa, AL 35487 USA. Syracuse Univ, Dept Chem, Syracuse, NY 13244 USA. RP Planalp, RP (reprint author), Kunsan Natl Univ, Sch Sci & Technol, 68,Miryongdong, Kusan 573701, Jeollabukdo, South Korea. EM roy.planalp@unh.edu RI Rogers, Robin/C-8265-2013 OI Rogers, Robin/0000-0001-9843-7494 NR 30 TC 8 Z9 8 U1 4 U2 9 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1434-1948 J9 EUR J INORG CHEM JI Eur. J. Inorg. Chem. PD OCT 7 PY 2005 IS 19 BP 3971 EP 3982 DI 10.1002/ejic.200500382 PG 12 WC Chemistry, Inorganic & Nuclear SC Chemistry GA 974GT UT WOS:000232580100023 ER PT J AU Kim, HP Kim, BG Letterio, J Leonard, WJ AF Kim, HP Kim, BG Letterio, J Leonard, WJ TI Smad-dependent cooperative regulation of interleukin 2 receptor alpha chain gene expression by T cell receptor and transforming growth factor-beta SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN LYMPHOCYTES-T; TGF-BETA; IL-2 RECEPTOR; TARGETED DISRUPTION; MOLECULAR-CLONING; PROMOTER REGION; POTENTIAL ROLE; KNOCKOUT MICE; ACTIVATION; ELEMENTS AB The interleukin 2 receptor alpha chain (IL-2R alpha) is a component of high affinity IL-2 receptors and thus critically regulates T cell growth and other lymphoid functions. Five positive regulatory regions together control lineage-restricted and activation-dependent IL-2R alpha induction in response to antigen and IL-2. We now show that TGF-beta cooperates with T cell receptor (TCR) signaling to increase IL-2R alpha gene expression. Moreover, we identify a sixth positive regulatory region that regulates IL-2R alpha expression in cells treated with anti-CD3 + anti-CD28 as well as TGF-beta and show that this region contains binding sites for Smad3, AP-1, and cAMP-responsive element-binding protein/ ATF proteins. The importance of Smad complexes is indicated by impaired IL-2R alpha induction by TGF-beta in CD4(+) T cells from both Smad3(-/-) and Smad4(-/-) mice. Thus, we have identified a novel positive regulatory region in the IL-2R alpha gene that mediates TGF-beta-dependent induction of the gene. These findings have implications related to IL-2R alpha expression on activated T cells and regulatory T cells. C1 NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. RP Leonard, WJ (reprint author), NHLBI, Lab Mol Immunol, NIH, Bldg 10,Rm 7N252, Bethesda, MD 20892 USA. EM wjl@helix.nih.gov NR 66 TC 25 Z9 29 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 7 PY 2005 VL 280 IS 40 BP 34042 EP 34047 DI 10.1074/jbc.M508833200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 969JF UT WOS:000232229700043 PM 16087671 ER PT J AU Halverson, KM Panchal, RG Nguyen, TL Gussio, R Little, SF Misakian, M Bavari, S Kasianowicz, JJ AF Halverson, KM Panchal, RG Nguyen, TL Gussio, R Little, SF Misakian, M Bavari, S Kasianowicz, JJ TI Anthrax biosensor, protective antigen ion channel asymmetric blockade SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SYMMETRICAL TETRAALKYLAMMONIUM IONS; PHOSPHOLIPID-BILAYER MEMBRANES; VOLTAGE-DEPENDENT BLOCK; PLANAR LIPID-BILAYERS; LETHAL FACTOR; TOXIN CHANNELS; MONOCLONAL-ANTIBODIES; CRYSTAL-STRUCTURE; MAMMALIAN-CELLS; FACTOR-BINDING AB The significant threat posed by biological agents ( e. g. anthrax, tetanus, botulinum, and diphtheria toxins) (Inglesby, T. V., O'Toole, T., Henderson, D. A., Bartlett, J. G., Ascher, M. S., Eitzen, E., Friedlander, A. M., Gerberding, J., Hauer, J., Hughes, J., McDade, J., Osterholm, M. T., Parker, G., Perl, T. M., Russell, P. K., and Tonat, K. ( 2002) J. Am. Med. Assoc. 287, 2236 - 2252) requires innovative technologies and approaches to understand the mechanisms of toxin action and to develop better therapies. Anthrax toxins are formed from three proteins secreted by fully virulent Bacillus anthracis, protective antigen (PA, 83 kDa), lethal factor (LF, 90 kDa), and edema factor (EF, 89 kDa). Here we present electrophysiological measurements demonstrating that full-length LF and EF convert the current-voltage relationship of the heptameric PA(63) ion channel from slightly nonlinear to highly rectifying and diode-like at pH 6.6. This effect provides a novel method for characterizing functional toxin interactions. The method confirms that a previously well characterized PA(63) monoclonal antibody, which neutralizes anthrax lethal toxin in animals in vivo and in vitro, prevents the binding of LF to the PA(63) pore. The technique can also detect the presence of anthrax lethal toxin complex from plasma of infected animals. The latter two results suggest the potential application of PA(63) nanopore-based biosensors in anthrax therapeutics and diagnostics. C1 Natl Inst Stand & Technol, Adv Chem Sci Lab, Gaithersburg, MD 20899 USA. Natl Inst Stand & Technol, Elect & Elect Engn Lab, Semicond Engn Div, Gaithersburg, MD 20899 USA. USA, Med Res Inst Infect Dis, Frederick, MD 21702 USA. NCI, Dev Therapeut Program, Target Struct Based Drug Discovery Grp, Sci Applicat Int Corp, Frederick, MD 21702 USA. RP Kasianowicz, JJ (reprint author), Natl Inst Stand & Technol, Adv Chem Sci Lab, Bldg 225,Rm B326, Gaithersburg, MD 20899 USA. EM john.kasianowicz@nist.gov NR 35 TC 56 Z9 56 U1 0 U2 14 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 7 PY 2005 VL 280 IS 40 BP 34056 EP 34062 DI 10.1074/jbc.M507928200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 969JF UT WOS:000232229700045 PM 16087661 ER PT J AU Ishaq, M DeGray, G Natarajan, V AF Ishaq, M DeGray, G Natarajan, V TI Evidence for the involvement of tyrosine kinase ZAP 70 in nuclear retinoid receptor-dependent transactivation in T lymphocytes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CELL ANTIGEN RECEPTOR; SIGNAL-TRANSDUCTION; X-RECEPTOR; PROTEIN; ACTIVATION; PHOSPHORYLATION; PHOSPHATASES; THYMOCYTES; FAMILY; ALPHA AB Retinoic acid receptors (RARs) and retinoid X receptors (RXRs) are transcription factors that control diverse cellular functions during development and homeostasis. The biochemical role of these proteins in T lymphocytes is not well known. Here we have studied the role of protein-tyrosine kinase ZAP70, a key enzyme involved in the proximal signaling events during T cell activation, in the modulation of RXRE- and RARE-dependent activation in T lymphocytes. Surprisingly, ZAP 70-negative Jurkat T cells showed considerable loss of both RXRE- and RARE-mediated transactivation as compared with wild type Jurkat cells. In addition, ZAP 70-negative cells failed to exhibit normal protein kinase C theta and calcineurin-induced transcriptional activity. ZAP 70-negative cells that were reconstituted with active ZAP 70 regained the transactivation function, whereas cells expressing kinase-dead form of ZAP 70 failed to do so. Defective transcriptional activation was also observed in actively proliferating human peripheral blood T lymphocytes in which RNA interference was used to induce loss of ZAP 70 expression. In addition, an Lck-deficient Jurkat cell line that cannot efficiently activate ZAP 70 was also found defective in RXRE- mediated transcription. Finally, RNA interference-induced loss of ZAP 70 or Lck protein in Jurkat cells resulted in significant decrease in the RXRE- dependent activation. Together, these results suggest a novel functional role for ZAP 70 in nuclear receptor-driven transactivation in T lymphocytes. C1 NCI, Mol Cell Biol Lab, SAIC, NIH, Frederick, MD 21702 USA. RP Ishaq, M (reprint author), NCI, Mol Cell Biol Lab, SAIC, NIH, Frederick, MD 21702 USA. EM mishaq@nih.gov FU NCI NIH HHS [N01-CO-12400] NR 23 TC 4 Z9 5 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 7 PY 2005 VL 280 IS 40 BP 34152 EP 34158 DI 10.1074/jbc.M501547200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 969JF UT WOS:000232229700056 PM 16096284 ER PT J AU Song, YT Masison, DC AF Song, YT Masison, DC TI Independent regulation of Hsp70 and Hsp90 chaperones by Hsp70/Hsp90-organizing protein Sti1 (Hop1) SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID YEAST SACCHAROMYCES-CEREVISIAE; STEROID-RECEPTOR ACTION; HEAT-SHOCK PROTEINS; PROGESTERONE-RECEPTOR; SIGNAL-TRANSDUCTION; IN-VIVO; BINDING; PROPAGATION; STRESS; PRION AB Hsp70 and Hsp90 protein chaperones cooperate in a protein-folding pathway required by many "client" proteins. The co-chaperone Sti1p coordinates functions of Hsp70 and Hsp90 in this pathway. Sti1p has three tetratricopeptide repeat (TPR) domains. TPR1 binds Hsp70, TPR2a binds Hsp90, and the ligand for TPR2b is unknown. Although Sti1p is thought to be dedicated to the client folding pathway, we earlier showed that Sti1p regulated Hsp70, independently of Hsp90, in a way that impairs yeast [PSI+] prion propagation. Using this prion system to monitor Sti1p regulation of Hsp70 and an Hsp90-inhibiting compound to monitor Hsp90 regulation, we identified Sti1p mutations that separately affect Hsp70 and Hsp90. TPR1 mutations impaired Sti1p regulation of Hsp70, but deletion of TPR2a and TPR2b did not. Conversely, TPR2a and TPR2b mutations impaired Sti1p regulation of Hsp90, but deletion of TPR1 did not. All Sti1p mutations variously impaired the client folding pathway, which requires both Hsp70 and Hsp90. Thus, Sti1p regulated Hsp70 and Hsp90 separately, Hsp90 is implicated as a TPR2b ligand, and mutations separately affecting regulation of either chaperone impair a pathway that is dependent upon both. We further demonstrate that client folding depended upon bridging of Hsp70 and Hsp90 by Sti1p and find conservation of the independent regulation of Hsp70 and Hsp90 by human Hop1. C1 NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. RP NIDDK, Lab Biochem & Genet, NIH, Bldg 8,Rm 407,8 Ctr Dr, Bethesda, MD 20892 USA. EM masisond@helix.nih.gov FU NIDDK NIH HHS [Z01 DK024946-08] NR 38 TC 58 Z9 58 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 7 PY 2005 VL 280 IS 40 BP 34178 EP 34185 DI 10.1074/jbc.M505420200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 969JF UT WOS:000232229700059 PM 16100115 ER PT J AU Zhou, XW Kafsack, BFC Cole, RN Beckett, P Shen, RF Carruthers, VB AF Zhou, XW Kafsack, BFC Cole, RN Beckett, P Shen, RF Carruthers, VB TI The opportunistic pathogen Toxoplasma gondii deploys a diverse legion of invasion and survival proteins SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Review ID NUCLEOSIDE TRIPHOSPHATE HYDROLASE; DENSE GRANULE PROTEIN; PARASITOPHOROUS VACUOLE MEMBRANE; HOST-CELL INVASION; MASS-SPECTROMETRY; MOLECULAR CHARACTERIZATION; MICRONEME PROTEIN; APICOMPLEXAN PARASITES; PLASMODIUM-FALCIPARUM; SURFACE-ANTIGEN AB Host cell invasion is an essential step during infection by Toxoplasma gondii, an intracellular protozoan that causes the severe opportunistic disease toxoplasmosis in humans. Recent evidence strongly suggests that proteins discharged from Toxoplasma apical secretory organelles (micronemes, dense granules, and rhoptries) play key roles in host cell invasion and survival during infection. However, to date, only a limited number of secretory proteins have been discovered, and the full spectrum of effector molecules involved in parasite invasion and survival remains unknown. To address these issues, we analyzed a large cohort of freely released Toxoplasma secretory proteins by using two complementary methodologies, two-dimensional electrophoresis/mass spectrometry and liquid chromatography/electrospray ionization-tandem mass spectrometry (MudPIT, shotgun proteomics). Visualization of Toxoplasma secretory products by two-dimensional electrophoresis revealed similar to 100 spots, most of which were successfully identified by protein microsequencing or matrix-assisted laser desorption ionization-mass spectrometry analysis. Many proteins were present in multiple species suggesting they are subjected to substantial posttranslational modification. Shotgun proteomic analysis of the secretory fraction revealed several additional products, including novel putative adhesive proteins, proteases, and hypothetical secretory proteins similar to products expressed by other related parasites including Plasmodium, the etiologic agent of malaria. A subset of novel proteins were re-expressed as fusions to yellow fluorescent protein, and this initial screen revealed shared and distinct localizations within secretory compartments of T. gondii tachyzoites. These findings provided a uniquely broad view of Toxoplasma secretory proteins that participate in parasite survival and pathogenesis during infection. C1 Johns Hopkins Bloomberg Sch Publ Hlth, W Harry Feinstone Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA. Johns Hopkins Sch Med, Baltimore, MD 21205 USA. NHLBI, NIH, Bethesda, MD 20892 USA. GE Healthcare, Piscataway, NJ 08855 USA. RP Carruthers, VB (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, W Harry Feinstone Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA. EM vcarruth@jhsph.edu OI Carruthers, Vern/0000-0001-6859-8895 FU NCRR NIH HHS [1S10-RR14702]; NIAID NIH HHS [R01 AI046675, R21 AI053797, R21AI053797] NR 119 TC 74 Z9 87 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 7 PY 2005 VL 280 IS 40 BP 34233 EP 34244 DI 10.1074/jbc.M504160200 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 969JF UT WOS:000232229700066 PM 16002397 ER PT J AU Lai, WS Carrick, DM Blackshear, PJ AF Lai, WS Carrick, DM Blackshear, PJ TI Influence of nonameric AU-rich tristetraprolin-binding sites on mRNA deadenylation and turnover SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ZINC-FINGER PROTEINS; ELEMENT; DEGRADATION; DOMAIN; HUR; DESTABILIZATION; STABILITY; MARCKS AB Tristetraprolin (TTP), a member of the tandem CCCH zinc finger protein family, promotes deadenylation of tumor necrosis factor-alpha and granulocyte-macrophage colony-stimulating factor mRNAs after binding to the AU-rich elements ( ARE) in their 3'-untranslated regions. The high affinity TTP-ARE binding occurs between the tandem zinc finger domain and the preferred nonamer UUAUUUAUU. By mutating a well defined core sequence of 24 bases from the tumor necrosis factor-alpha ARE, we compared the influence of four possible nonameric TTP-binding sites in the wildtype ARE with that of a single binding site in the mutated probe on the binding of TTP to the RNA and the subsequent deadenylation of the poly( A) tail. By inserting this 24-base ARE into an otherwise stable transcript, we also attempted to determine the extent of the instability conferred by the presence of one or two TTP-binding sites. These sites were created or modified by mutating the As in the UUAUUUAUU nonamer or by changing the central U in the nonamer, in both cases to C residues. The results suggest that even a single nonamer TTP-binding site can confer at least partial sensitivity to the TTP-mediated mRNA turnover on an otherwise stable mRNA, but that two binding sites make the transcript much more unstable. Even though the central U of the nonamer binding site was predicted by structural studies possibly to permit base substitution, mutation of this U to C greatly inhibited the binding of TTP to the ARE, thus reducing the ability of the TTP to promote deadenylation and instability of the mRNA. C1 NIEHS, Neurobiol Lab, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Off Clin Res, NIH, Res Triangle Pk, NC 27709 USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Biochem, Durham, NC 27710 USA. RP Blackshear, PJ (reprint author), NIEHS, Neurobiol Lab, NIH, A2-05,111 Alexander Dr, Res Triangle Pk, NC 27709 USA. EM Black009@niehs.nih.gov NR 21 TC 39 Z9 40 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 7 PY 2005 VL 280 IS 40 BP 34365 EP 34377 DI 10.1074/jbc.M506757200 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 969JF UT WOS:000232229700080 PM 16061475 ER PT J AU Zhao, MB Ito, Y Tu, PF AF Zhao, MB Ito, Y Tu, PF TI Isolation of a novel flavanone 6-glucoside from the flowers of Carthamus tinctorium (Honghua) by high-speed counter-current chromatography SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE Carthamus tinctorium; high-speed counter-current chromatography; (2S)-4 ',5,6,7-tetrahydroxyflavavone 6-O-beta-D-glucopyranoside ID L. OIL CAKE AB A novel flavanone glycoside, (2S)-4',5,6,7-tetrahydroxyflavavone 6-O-beta-(D)-glucopyranoside was isolated from the ethyl acetate extract of the flowers of Carthamus tinctorium by high-speed counter-current chromatography (HSCCC). Using an optimized two-phase solvent system composed of ethyl acetate-methanol-water (5:1:5, v/v), target compound (52 mg) with purity of 98.0% was obtained from 2.0 g of sample by HSCCC in seven times run. The structure of the target compound was elucidated by means of spectroscopic methods including IR, MS, 1D and 2D NMR techniques. (c) 2005 Elsevier B.V. All rights reserved. C1 Peking Univ, Hlth Sci Ctr, Sch Pharmaceut Sci, Beijing 100083, Peoples R China. NHLBI, Ctr Biochem & Biophys, NIH, Bethesda, MD 20892 USA. RP Tu, PF (reprint author), Peking Univ, Hlth Sci Ctr, Sch Pharmaceut Sci, Beijing 100083, Peoples R China. EM pengfeitu@bjmu.edu.cn NR 11 TC 14 Z9 23 U1 0 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD OCT 7 PY 2005 VL 1090 IS 1-2 BP 193 EP 196 DI 10.1016/j.chroma.2005.07.010 PG 4 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 963CQ UT WOS:000231781100022 PM 16196150 ER PT J AU Ronning, DR Guynet, C Ton-Hoang, B Perez, ZN Ghirlando, R Chandler, M Dyda, F AF Ronning, DR Guynet, C Ton-Hoang, B Perez, ZN Ghirlando, R Chandler, M Dyda, F TI Active site sharing and subterminal hairpin recognition in a new class of DNA transposases SO MOLECULAR CELL LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; HELICOBACTER-PYLORI; INSERTION-SEQUENCE; PATHOGENICITY ISLAND; CRYSTAL-STRUCTURE; SYNAPTIC COMPLEX; BINDING PROTEINS; NUCLEASE DOMAIN; MU-TRANSPOSASE; DRAFT SEQUENCE AB Many bacteria harbor simple transposable elements termed insertion sequences (IS). In Helicobacter pylori, the chimeric IS605 family elements are particularly interesting due to their proximity to genes encoding gastric epithelial invasion factors. Protein sequences of IS605 transposases do not bear the hallmarks of other well-characterized transposases. We have solved the crystal structure of full-length transposase (TnpA) of a representative member, ISHp6O8. Structurally, TnpA does not resemble any characterized transposase; rather, it is related to rolling circle replication (RCR) proteins. Consistent with RCR, Mg(2+) and a conserved tyrosine, Tyr-127, are essential for DNA nicking and the formation of a covalent intermediate between TnpA and DNA. TnpA is dimeric, contains two shared active sites, and binds two DNA stem loops representing the conserved inverted repeats near each end of ISHp6O8. The cocrystal structure with stem-loop DNA illustrates how this family of transposases specifically recognizes and pairs ends, necessary steps during transposition. C1 NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. CNRS, F-31062 Toulouse, France. RP Dyda, F (reprint author), NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. EM fred.dyda@nih.gov RI Ghirlando, Rodolfo/A-8880-2009; Guynet, Catherine/A-4815-2011; OI Chandler, Michael/0000-0002-0292-6662 NR 56 TC 48 Z9 49 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD OCT 7 PY 2005 VL 20 IS 1 BP 143 EP 154 DI 10.1016/j.molcel.2005.07.026 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 973HW UT WOS:000232514500014 PM 16209952 ER PT J AU Lee, JY Chang, J Joseph, N Ghirlando, R Rao, DN Yang, W AF Lee, JY Chang, J Joseph, N Ghirlando, R Rao, DN Yang, W TI MutH complexed with hemi- and unmethylated DNAs: Coupling base recognition and DNA cleavage SO MOLECULAR CELL LA English DT Article ID RESTRICTION-ENDONUCLEASE BAMHI; SUBSTRATE-ASSISTED CATALYSIS; SITE-DIRECTED MUTAGENESIS; COLI MISMATCH REPAIR; ESCHERICHIA-COLI; CRYSTAL-STRUCTURE; ECORV ENDONUCLEASE; STRUCTURAL BASIS; ACTIVE-SITES; COGNATE DNA AB MutH initiates mismatch repair by nicking the transiently unmethylated daughter strand 5' to a GATC sequence. Here, we report crystal structures of MutH complexed with hemimethylated and unmethylated GATC substrates. Both structures contain two Ca2+ ions jointly coordinated by a conserved aspartate and the scissile phosphate, as observed in the restriction endonucleases BamHI and BgII. In the hemimethylated complexes, the active site is more compact and DNA cleavage is more efficient. The Lys residue in the conserved DEK motif coordinates the nucleophilic water in conjunction with the phosphate 3' to the scissile bond; the same Lys is also hydrogen bonded with a carbonyl oxygen in the DNA binding module. We propose that this Lys, which is conserved in many restriction endonucleases and is replaced by Glu or Gin in BamHI and BgIII, is a sensor for DNA binding and the linchpin that couples base recognition and DNA cleavage. C1 NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Indian Inst Sci, Dept Biochem, Bangalore 560012, Karnataka, India. RP Yang, W (reprint author), NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. EM wei.yang@nih.gov RI Ghirlando, Rodolfo/A-8880-2009; Yang, Wei/D-4926-2011 OI Yang, Wei/0000-0002-3591-2195 NR 52 TC 50 Z9 53 U1 0 U2 8 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD OCT 7 PY 2005 VL 20 IS 1 BP 155 EP 166 DI 10.1016/j.molcel.2005.08.019 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 973HW UT WOS:000232514500015 PM 16209953 ER PT J AU Terracciano, A Abdel-Khalek, AM Adam, N Adamovova, L Ahn, C Ahn, HN Alansari, BM Alcalay, L Allik, J Angleitner, A Avia, MD Ayearst, LE Barbaranelli, C Beer, A Borg-Cunen, MA Bratko, D Brunner-Sciarra, M Budzinski, L Camart, N Dahourou, D De Fruyt, F de Lima, MP del Pilar, GEH Diener, E Falzon, R Fernando, K Fickova, E Fischer, R Flores-Mendoza, C Ghayur, MA Gulgoz, S Hagberg, B Halberstadt, J Halim, MS Hrebickova, M Humrichouse, J Jensen, HH Jocic, DD Jonsson, FH Khoury, B Klinkosz, W Knezevic, G Lauri, MA Leibovich, N Martin, TA Marusic, I Mastor, KA Matsumoto, D McRorie, M Meshcheriakov, B Mortensen, EL Munyae, M Nagy, J Nakazato, K Nansubuga, F Oishi, S Ojedokun, AO Ostendorf, F Paulhus, DL Pelevin, S Petot, JM Podobnik, N Porrata, JL Pramila, VS Prentice, G Realo, A Reategui, N Rolland, JP Rossier, J Ruch, W Rus, VS Sanchez-Bernardos, ML Schmidt, V Sciculna-Calleja, S Sekowski, A Shakespeare-Finch, J Shimonaka, Y Simonetti, F Sineshaw, T Siuta, J Smith, PB Trapnell, PD Trobst, KK Wang, L Yik, M Zupancic, A McCrae, RR AF Terracciano, A Abdel-Khalek, AM Adam, N Adamovova, L Ahn, C Ahn, HN Alansari, BM Alcalay, L Allik, J Angleitner, A Avia, MD Ayearst, LE Barbaranelli, C Beer, A Borg-Cunen, MA Bratko, D Brunner-Sciarra, M Budzinski, L Camart, N Dahourou, D De Fruyt, F de Lima, MP del Pilar, GEH Diener, E Falzon, R Fernando, K Fickova, E Fischer, R Flores-Mendoza, C Ghayur, MA Gulgoz, S Hagberg, B Halberstadt, J Halim, MS Hrebickova, M Humrichouse, J Jensen, HH Jocic, DD Jonsson, FH Khoury, B Klinkosz, W Knezevic, G Lauri, MA Leibovich, N Martin, TA Marusic, I Mastor, KA Matsumoto, D McRorie, M Meshcheriakov, B Mortensen, EL Munyae, M Nagy, J Nakazato, K Nansubuga, F Oishi, S Ojedokun, AO Ostendorf, F Paulhus, DL Pelevin, S Petot, JM Podobnik, N Porrata, JL Pramila, VS Prentice, G Realo, A Reategui, N Rolland, JP Rossier, J Ruch, W Rus, VS Sanchez-Bernardos, ML Schmidt, V Sciculna-Calleja, S Sekowski, A Shakespeare-Finch, J Shimonaka, Y Simonetti, F Sineshaw, T Siuta, J Smith, PB Trapnell, PD Trobst, KK Wang, L Yik, M Zupancic, A McCrae, RR TI National character does not reflect mean personality trait levels in 49 cultures SO SCIENCE LA English DT Article ID STEREOTYPES; ACCURACY AB Most people hold beliefs about personality characteristics typical of members of their own and others' cultures. These perceptions of national character may be generalizations from personal experience, stereotypes with a "kernel of truth," or inaccurate stereotypes. We obtained national character ratings of 3989 people from 49 cultures and compared them with the average personality scores of culture members assessed by observer ratings and self-reports. National character ratings were reliable but did not converge with assessed traits. Perceptions of national character thus appear to be unfounded stereotypes that may serve the function of maintaining a national identity. C1 NIA, NIH, DHHS, Gerontol Res Ctr, Baltimore, MD 21224 USA. Kuwait Univ, Fac Social Sci, Dept Psychol, Kaifan 71962, Kuwait. Eotvos Lorand Univ, Fac Educ & Psychol, H-1075 Budapest, Hungary. Slovak Acad Sci, Inst Expt Psychol, Bratislava 81364, Slovakia. Pusan Natl Univ, Dept Educ, Pusan 609735, South Korea. Pusan Natl Univ, Dept Psychol, Pusan 609735, South Korea. Pontificia Univ Catolica Chile, Escuela Psicol, Santiago, Chile. Univ Tartu, Dept Psychol, EE-50090 Tartu, Estonia. Univ Bielefeld, Dept Psychol, D-33501 Bielefeld, Germany. Univ Complutense Madrid, Fac Psicol, Madrid, Spain. York Univ, Dept Psychol, N York, ON M3J 1P3, Canada. Univ Roma La Sapienza, Dept Psychol, I-00185 Rome, Italy. Univ Iowa, Dept Psychol, Iowa City, IA 52242 USA. Univ Malta, Dept Psychol, Msida MSD 06, Malta. Univ Zagreb, Filozofski Fak, Dept Psychol, HR-10002 Zagreb, Croatia. Univ Peruana Cayetano Heredia, Fac Psicol, Lima, Peru. Univ Melbourne, Dept Psychol, Parkville, Vic 3010, Australia. Univ Paris 10, Lab Psychol Clin Faits Culturels, F-92001 Nanterre, France. Univ Ouagadougou, Dept Psychol, Ouagadougou 03, Burkina Faso. Dept Psychol, B-9000 Ghent, Belgium. Univ Coimbra, Fac Psicol Ciencias Educacao, Coimbra, Portugal. Univ Philippines, Dept Psychol, Quezon City 1101, Philippines. Univ Illinois, Dept Psychol, Champaign, IL 61820 USA. Univ Otago, Dept Psychol, Dunedin, New Zealand. Victoria Univ Wellington, Sch Psychol, Wellington, New Zealand. Univ Fed Minas Gerais, Dept Psicol, Belo Horizonte, MG, Brazil. Al Akhawayn Univ, Ifrane, Morocco. Koc Univ, TR-80910 Istanbul, Turkey. Lund Univ, Unit Gerontol & Care Elderly, S-22220 Lund, Sweden. Atma Jaya Indonesia Catholic Univ, Fac Psychol, Jakarta 12930, Indonesia. Acad Sci Czech Republic, Brno 60200, Czech Republic. Univ Copenhagen, Inst Publ Hlth, Dept Hlth Psychol, DK-2200 Copenhagen, Denmark. Inst Psychiat, Belgrade, Serbia Monteneg. Univ Iceland, Fac Social Sci, IS-101 Reykjavik, Iceland. Amer Univ Beirut, Med Ctr, Dept Psychiat, Beirut 1107 2020, Lebanon. Catholic Univ Lublin, Dept Psychol, PL-20950 Lublin, Poland. Univ Belgrade, Dept Psychol, YU-11000 Belgrade, Serbia Monteneg. Univ Buenos Aires, Fac Psychol, Buenos Aires, DF, Argentina. Susquehanna Univ, Dept Psychol, Selinsgrove, PA 17870 USA. Univ Kebangsaan Malaysia, Ctr Gen Studies, Selangor, Darul Ehsan, Malaysia. San Francisco State Univ, Dept Psychol, San Francisco, CA 94132 USA. Queens Univ Belfast, Sch Psychol, Belfast BT7 1NN, Antrim, North Ireland. Int Univ Dubna, Dept Psychol, Dubna 141980, Russia. Univ Botswana, Ctr Continuing Educ, Gaborone, Botswana. Iwate Prefectural Univ, Dept Psychol, Takizawa, Iwate 0200193, Japan. Makerere Univ, Dept Org Psychol, Kampala, Uganda. Univ Virginia, Dept Psychol, Charlottesville, VA 22904 USA. Univ Ibadan, Dept Psychol, Ibadan, Nigeria. Univ British Columbia, Dept Psychol, Vancouver, BC V6T 1Z4, Canada. Psychiat Hosp Idrija, Idrija 5280, Slovenia. Univ Puerto Rico, Escuela Grad Adm Publ, Rio Piedras, PR 00931 USA. Andhra Univ, Dept Psychol, Visakhapatnam 530003, Andhra Pradesh, India. Univ Paris 10, STAPS Dept, F-92001 Nanterre, France. Univ Lausanne, Inst Psychol, CH-1015 Lausanne, Switzerland. Inst Psychol, CH-8044 Zurich, Switzerland. Univ Ljubljana, Fac Arts, Ljubljana, Slovenia. Queensland Univ Technol, Sch Psychol & Counselling, Brisbane, Qld, Australia. Bunkyo Gakuin Univ, Dept Psychol, Oi Machi, Saitama 3568533, Japan. Ramapo Coll, Dept Psychol, Mahwah, NJ 07430 USA. Jagiellonian Univ, Inst Psychol, Krakow, Poland. Univ Sussex, Dept Psychol, Brighton, E Sussex, England. Univ Winnipeg, Dept Psychol, Winnipeg, MB R3B 2E9, Canada. Peking Univ, Dept Psychol, Beijing 100871, Peoples R China. Hong Kong Univ Sci & Technol, Div Social Sci, Kowloon, Hong Kong, Peoples R China. Minist Hlth, Ljubljana 1000, Slovenia. RP Terracciano, A (reprint author), NIA, NIH, DHHS, Gerontol Res Ctr, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM terraccianoa@grc.nia.nih.gov; mccraej@grc.nia.nih.gov RI terracciano, antonio/B-1884-2008; De Fruyt, Filip/A-3083-2009; Rossier, Jerome/A-3494-2009; Allik, Juri/D-5609-2009; Sanchez-Bernardos, Maria Luisa/C-6038-2011; Avia, Maria Dolores/C-7061-2011; Hrebickova, Martina/H-4410-2014; Wang, Lei/D-2501-2016; Marusic, Ivan/M-1903-2015; Realo, Anu/M-9524-2016; Ruch, Willibald/G-3124-2011 OI Mortensen, Erik Lykke/0000-0002-6985-451X; Rossier, Jerome/0000-0002-9924-3672; Allik, Juri/0000-0002-8358-4747; Sanchez-Bernardos, Maria Luisa/0000-0003-4931-867X; Hrebickova, Martina/0000-0003-4356-567X; Wang, Lei/0000-0002-6156-9028; Marusic, Ivan/0000-0003-2700-8435; Ruch, Willibald/0000-0001-5368-3616 FU Intramural NIH HHS [ZIA AG000180-25, Z99 AG999999, ZIA AG000180-26] NR 28 TC 184 Z9 185 U1 7 U2 68 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD OCT 7 PY 2005 VL 310 IS 5745 BP 96 EP 100 DI 10.1126/science.1117199 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 972TV UT WOS:000232477000045 PM 16210536 ER PT J AU Yogeeswari, P Sriram, D Thirumurugan, R Raghavendran, JV Sudhan, K Pavana, RK Stables, J AF Yogeeswari, P Sriram, D Thirumurugan, R Raghavendran, JV Sudhan, K Pavana, RK Stables, J TI Discovery of N-(2,6-dimethylphenyl)-substituted semicarbazones as anticonvulsants: Hybrid pharmacophore-based design SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID ANTIEPILEPTIC DRUG DEVELOPMENT; MAXIMAL ELECTROSHOCK SCREEN; ARYL SEMICARBAZONES; AMINO GROUP; AGENTS; ARYLSEMICARBAZONES; HEPATOTOXICITY; DERIVATIVES; EPILEPSY; SEIZURES AB Epilepsy is the most common primary neurological disorder known. In the past decade, various aryl semicarbazones have been designed that were structurally dissimilar from many common anticonvulsants containing the dicarboximide function (CONRCO), which may contribute to toxic side effects. In the present work various N-4-(2,6-dimethylphenyl) semicarbazones were designed as pharmacophore hybrids between the aryl semicarbazones and ameltolide. A three-dimensional four-point pharmacophore model was developed for anticonvulsants, and the title compounds were found to match with ralitoline. All of the compounds exhibited anticonvulsant activity in the maximal electroshock test when administered by both intraperitoneal and oral routes. Compound N-1-(2,6-dimethylphenyl)-N-4-(2-hydroxybenzaldehyde) semicarbazone (9) emerged as a prototype with wide spectrum anticonvulsant agent active in five models of seizure with no neurotoxicity and hepatotoxicity. Compound 9 increased the 4-aminobutyric acid (GABA) level by 118% and inhibited the GABA transaminase enzyme both in vitro and ex vivo. C1 Birla Inst Technol & Sci, Med Chem Res Lab, Pharm Grp, Pilani 333031, Rajasthan, India. NIH, Preclin Pharmacol Sect, Epilepsy Branch, Bethesda, MD 20892 USA. RP Yogeeswari, P (reprint author), Birla Inst Technol & Sci, Med Chem Res Lab, Pharm Grp, Pilani 333031, Rajasthan, India. EM pyogee@bits-pilani.ac.in RI Pavana, Roheeth/F-5839-2017; OI Pavana, Roheeth/0000-0001-6256-3683; Rathinasabapathy, Thirumurugan/0000-0002-7330-0552 NR 58 TC 101 Z9 104 U1 1 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD OCT 6 PY 2005 VL 48 IS 20 BP 6202 EP 6211 DI 10.1021/jm050283b PG 10 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 971TC UT WOS:000232406600005 PM 16190747 ER PT J AU Ahn, S Joyner, AL AF Ahn, S Joyner, AL TI In vivo analysis of quiescent adult neural stem cells responding to Sonic hedgehog SO NATURE LA English DT Article ID MAMMALIAN BRAIN; PROGENITOR PROLIFERATION; SUBVENTRICULAR ZONE; DENTATE GYRUS; HIPPOCAMPUS; PRECURSORS; NEURONS; NEUROGENESIS; REGENERATION; ASTROCYTES AB Sonic hedgehog (Shh) has been implicated in the ongoing neurogenesis in postnatal rodent brains(1,2). Here we adopted an in vivo genetic fate-mapping strategy, using Gli1 (GLI-Kruppel family member) as a sensitive readout of Shh activity, to systematically mark and follow the fate of Shh-responding cells in the adult mouse forebrain. We show that initially, only a small population of cells ( including both quiescent neural stem cells and transit-amplifying cells) responds to Shh in regions undergoing neurogenesis. This population subsequently expands markedly to continuously provide new neurons in the forebrain. Our study of the behaviour of quiescent neural stem cells provides in vivo evidence that they can self-renew for over a year and generate multiple cell types. Furthermore, we show that the neural stem cell niches in the subventricular zone and dentate gyrus are established sequentially and not until late embryonic stages. C1 NYU, Sch Med, Howard Hughes Med Inst, Dev Genet Program,Skirball Inst Biomol Med, New York, NY 10016 USA. NYU, Sch Med, Dept Cell Biol, New York, NY 10016 USA. NYU, Sch Med, Dept Physiol & Neurosci, New York, NY 10016 USA. RP Joyner, AL (reprint author), NICHHD, Unit Dev Neurogenet, Lab Mammalian Genes & Dev, NIH, 9000 Rockville Pike,Bldg 6B, Bethesda, MD 20892 USA. EM joyner@saturn.med.nyu.edu NR 27 TC 402 Z9 420 U1 1 U2 20 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD OCT 6 PY 2005 VL 437 IS 7060 BP 894 EP 897 DI 10.1038/nature03994 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 970VB UT WOS:000232338600048 PM 16208373 ER PT J AU Dubois-Dalcq, M Ffrench-Constant, C Franklin, RJM AF Dubois-Dalcq, M Ffrench-Constant, C Franklin, RJM TI Enhancing central nervous system remyelination in multiple sclerosis SO NEURON LA English DT Review ID AUTOIMMUNE ENCEPHALOMYELITIS; CNS DEMYELINATION; REPAIR; MODEL; REEXPRESSION; MYELINATION; LESIONS AB Recent studies on adult neural stem cells and the developmental biology of myelination have generated the expectation that neural precursors can repair the damaged central nervous system of multiple sclerosis patients where the endogenous remyelination process has failed. As a result, many laboratories are engaged in translational studies in which the goal is to design ways to promote remyelination and repair. Here we raise issues highlighted by prior experimental and human work that should be considered lest these studies become "lost in translation." C1 NINDS, NIH, Bethesda, MD 20892 USA. Univ Cambridge, Dept Pathol, Cambridge CB2 1TN, England. Univ Cambridge, Dept Vet Med, Cambridge CB2 1TN, England. Univ Cambridge, Cambridge Ctr Brain Repair, Cambridge CB2 1TN, England. RP Dubois-Dalcq, M (reprint author), NINDS, NIH, Bethesda, MD 20892 USA. EM dalcqm@mail.nih.gov; rjf1000@cam.ac.uk NR 25 TC 76 Z9 80 U1 1 U2 6 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD OCT 6 PY 2005 VL 48 IS 1 BP 9 EP 12 DI 10.1016/j.neuron.2005.09.004 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 974XW UT WOS:000232625700004 PM 16202704 ER PT J AU Castro, O Gladwin, MT AF Castro, O Gladwin, MT TI Case 17-2005: Acute chest syndrome and ARDS SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 Howard Univ, Ctr Sickle Cell Dis, Washington, DC 20059 USA. NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Castro, O (reprint author), Howard Univ, Ctr Sickle Cell Dis, Washington, DC 20059 USA. EM olcastro@aol.com NR 3 TC 1 Z9 1 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 6 PY 2005 VL 353 IS 14 BP 1529 EP 1529 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 970LZ UT WOS:000232313000028 PM 16207862 ER PT J AU Jeong, SJ Pise-Masison, CA Radonovich, MF Park, HU Brady, JN AF Jeong, SJ Pise-Masison, CA Radonovich, MF Park, HU Brady, JN TI Activated AKT regulates NF-kappa B activation, p53 inhibition and cell survival in HTLV-1-transformed cells SO ONCOGENE LA English DT Article DE HTLV-1; p53; NF-kappa B; AKT; p65; IKK ID VIRUS TYPE-I; SERINE-THREONINE KINASE; HTLV-I; PHOSPHATIDYLINOSITOL 3-KINASE; TRANSCRIPTIONAL ACTIVITY; CLINICAL ENTITY; HUMAN CANCER; IKK-BETA; PATHWAY; LEUKEMIA AB AKT activation enhances resistance to apoptosis and induces cell survival signaling through multiple downstream pathways. We now present evidence that AKT is activated in HTLV-1-transformed cells and that Tax activation of AKT is linked to NF-kappa B activation, p53 inhibition and cell survival. Overexpression of AKT wild type (WT), but not a kinase dead (KD) mutant, resulted in increased Tax-mediated NF-kappa B activation. Blocking AKT with the PI3K/AKT inhibitor LY294002 or AKT SiRNA prevented NF-kappa B activation and inhibition of p53. Treatment of C81 cells with LY294002 resulted in an increase in the p53-responsive gene MDM2, suggesting a role for AKT in the Tax-mediated regulation of p53 transcriptional activity. Further, we show that LY294002 treatment of C81cells abrogates in vitro IKK beta phosphorylation of p65 and causes a reduction of p65 Ser-536 phosphorylation in vivo, steps critical to p53 inhibition. Interestingly, blockage of AKT function did not affect IKKb phosphorylation of I kappa Ba in vitro suggesting selective activity of AKT on the IKKb complex. Finally, AKT prosurvival function in HTLV-1-transformed cells is linked to expression of Bcl-xL. We suggest that AKT plays a role in the activation of prosurvival pathways in HTLV-1-transformed cells, possibly through NF-kappa B activation and inhibition of p53 transcription activity. C1 Natl Canc Inst, Virus Tumor Biol Sect, Cellular Oncol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Brady, JN (reprint author), Natl Canc Inst, Virus Tumor Biol Sect, Cellular Oncol Lab, Ctr Canc Res,NIH, Bldg 41-B201,9000 Rockville Pike, Bethesda, MD 20892 USA. EM bradyj@exchange.nih.gov NR 44 TC 129 Z9 137 U1 0 U2 10 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD OCT 6 PY 2005 VL 24 IS 44 BP 6719 EP 6728 DI 10.1038/sj.onc.1208825 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 971FL UT WOS:000232367800013 PM 16007163 ER PT J AU Bhattacharya, B Cai, JL Luo, YQ Miura, T Mejido, J Brimble, SN Zeng, XM Schulz, TC Rao, MS Puri, RK AF Bhattacharya, B Cai, JL Luo, YQ Miura, T Mejido, J Brimble, SN Zeng, XM Schulz, TC Rao, MS Puri, RK TI Comparison of the gene expression profile of undifferentiated human embryonic stem cell lines and differentiating embryoid bodies SO BMC DEVELOPMENTAL BIOLOGY LA English DT Article ID IN-VITRO; MICROARRAY ANALYSIS; HUMAN BLASTOCYSTS; GROWTH-FACTORS; SELF-RENEWAL; IDENTIFICATION; PLURIPOTENCY; CLONING; MOUSE; CARDIOMYOCYTES AB Background: The identification of molecular pathways of differentiation of embryonic stem cells (heSC) is critical for the development of stem cell based medical therapies. In order to identify biomarkers and potential regulators of the process of differentiation, a high quality microarray containing 16,659 seventy base pair oligonucleotides was used to compare gene expression profiles of undifferentiated hESC lines and differentiating embryoid bodies. Results: Previously identified '' stemness '' genes in undifferentiated hESC lines showed down modulation in differentiated cells while expression of several genes was induced as cells differentiated. In addition, a subset of 194 genes showed overexpression of greater than >= 3 folds in human embryoid bodies (hEB). These included 37 novel and 157 known genes. Gene expression was validated by a variety of techniques including another large scale array, reverse transcription polymerase chain reaction, focused cDNA microarrays, massively parallel signature sequencing (MPSS) analysis and immunocytochemisty. Several novel hEB specific expressed sequence tags ( ESTs) were mapped to the human genome database and their expression profile characterized. A hierarchical clustering analysis clearly depicted a distinct difference in gene expression profile among undifferentiated and differentiated hESC and confirmed that microarray analysis could readily distinguish them. Conclusion: These results present a detailed characterization of a unique set of genes, which can be used to assess the hESC differentiation. C1 US FDA, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Bresagen Inc, Athens, GA USA. NIA, Neurosci Lab, Baltimore, MD 21224 USA. Natl Inst Drug Abuse, NIH, Bethesda, MD 20892 USA. RP Puri, RK (reprint author), US FDA, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. EM Bhattacharya@cber.fda.gov; CaiJi@grc.nia.nih.gov; LuoYo@grc.nia.nih.gov; miurat@grc.nia.nih.gov; jmejido@niaid.nih.gov; sbrimble@novocell.com; Xzeng@intra.nida.nih.gov; tjschulz@novocell.com; raomah@grc.nia.nih.gov; puri@cber.fda.gov NR 44 TC 83 Z9 86 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-213X J9 BMC DEV BIOL JI BMC Dev. Biol. PD OCT 5 PY 2005 VL 5 AR 22 DI 10.1186/1471-213X-5-22 PG 16 WC Developmental Biology SC Developmental Biology GA 997WR UT WOS:000234280000001 PM 16207381 ER PT J AU Shah, MR Hasselblad, V Stevenson, LW Binanay, C O'Connor, CM Sopko, G Califf, RM AF Shah, MR Hasselblad, V Stevenson, LW Binanay, C O'Connor, CM Sopko, G Califf, RM TI Impact of the pulmonary artery catheter in critically ill patients - Meta-analysis of randomized clinical trials SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Review ID RESPIRATORY-DISTRESS-SYNDROME; ADVANCED HEART-FAILURE; RISK SURGICAL PATIENTS; VASCULAR-SURGERY; MORBIDITY; THERAPY; CARE; MANAGEMENT; SURVIVORS AB Context Randomized clinical trials (RCTs) evaluating the pulmonary artery catheter (PAC) have been limited by small sample size. Some nonrandomized studies suggest that PAC use is associated with increased morbidity and mortality. Objective To-estimate the impact of the PAC device in critically ill patients. Data Sources MEDLINE (1985-2005), the Cochrane Controlled Trials Registry (19882005), the National Institutes of Health ClinicalTrials.gov database, and the US Food and Drug Administration Web site for RCTs in which patients Were randomly assigned to PAC or no PAC were searched. Results from the ESCAPE trial of patients with severe heart failure were also included. Search terms included pulmonary artery catheter, right heart catheter, catheter, and Swan-Ganz. Study Selection Eligible studies included patients who were undergoing surgery, in the intensive care unit (ICU), admitted with advanced heart failure, or diagnosed with acute respiratory distress syndrome and/or sepsis; and studies that reported death and the number of days hospitalized or the number of days in the ICU as outcome measures. Data Extraction Information on eligibility criteria, baseline characteristics, interventions, outcomes, and methodological quality was extracted by 2 reviewers. Disagreements were resolved by consensus. Data Synthesis In 13 RCTs, 5051 patients were randomized. Hemodynamic goals and treatment strategies varied among trials. A random-effects model was used to estimate the odds ratios (ORs) for death, number of days hospitalized, and use of inotropes and intravenous vasodilators. The combined OR foe mortality was 1.04 (95% confidence interval [CI], 0.90-1.20; P=.59). The difference in the mean number of days hospitalized for PAC minus the mean for no PAC was 0.11 (95% CI, -0.51 to 0.74; P=73). Use of the PAC was associated with a higher use of inotropes (OR, 1.58; 95% CI, 1.19-2.12; P=.002) and intravenous vasodilators (OR, 2.35; 95% CI, 1.75-3.15; P<.001). Conclusions In critically ill patients, use of the PAC neither increased overall mortality or days in hospital nor conferred benefit. Despite almost 20 years of RCTs, a clear strategy leading to improved survival with the PAC has not been devised. The neutrality of the PAC for clinical outcomes may result from the absence of effective evidence-based treatments to use in combination with PAC information across the spectrum of critically ill patients. C1 Duke Clin Res Inst, Biostat & Bioinformat, Durham, NC 27705 USA. Columbia Univ, Med Ctr, Dept Cardiol, New York, NY USA. Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. Duke Clin Res Inst, Project Leadership, Durham, NC 27705 USA. Duke Univ, Med Ctr, Div Cardiol, Durham, NC 27710 USA. NHLBI, Div Heart & Vasc Dis, NIH, Bethesda, MD 20892 USA. RP Hasselblad, V (reprint author), Duke Clin Res Inst, Biostat & Bioinformat, POB 17969, Durham, NC 27705 USA. EM victor.hasselblad@duke.edu NR 33 TC 277 Z9 302 U1 2 U2 10 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD OCT 5 PY 2005 VL 294 IS 13 BP 1664 EP 1670 DI 10.1001/jama.294.13.1664 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 970DC UT WOS:000232284400019 PM 16204666 ER PT J AU MacLennan, A Nelson, KB Hankins, G Speer, M AF MacLennan, A Nelson, KB Hankins, G Speer, M TI Who will deliver our grandchildren? Implications of cerebral palsy litigation SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID MALPRACTICE; INTRAPARTUM; INSURANCE; INFANTS; CRISIS C1 NINDS, Neuroepidemiol Branch, NIH, Bethesda, MD 20892 USA. Univ Adelaide, Womens & Childrens Hosp, Dept Obstet & Gynaecol, Adelaide, SA, Australia. Univ Texas, Med Branch, Dept Obstet, Galveston, TX 77550 USA. Baylor Coll Med, Dept Pediat, Sect Neonatol, Houston, TX 77030 USA. RP Nelson, KB (reprint author), NINDS, Neuroepidemiol Branch, NIH, Bldg 10,Room 5S221, Bethesda, MD 20892 USA. EM knelson@helix.nih.gov NR 32 TC 44 Z9 44 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD OCT 5 PY 2005 VL 294 IS 13 BP 1688 EP 1690 DI 10.1001/jama.294.13.1688 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 970DC UT WOS:000232284400022 PM 16204669 ER PT J AU Beisel, KW Rocha-Sanchez, SM Morris, KA Nie, LP Feng, F Kachar, B Yamoah, EN Fritzsch, B AF Beisel, KW Rocha-Sanchez, SM Morris, KA Nie, LP Feng, F Kachar, B Yamoah, EN Fritzsch, B TI Differential expression of KCNQ4 in inner hair cells and sensory neurons is the basis of progressive high-frequency hearing loss SO JOURNAL OF NEUROSCIENCE LA English DT Article DE potassium channel; Kcnq4; inner ear; hair cells; progressive high-frequency hearing loss; immunofluorescence; quantitative RT-PCR ID LONG-QT-SYNDROME; LANGE-NIELSEN-SYNDROME; GUINEA-PIG COCHLEA; POTASSIUM CHANNEL; DEVELOPMENTAL-CHANGES; DFNA2/KCNQ4 FAMILY; DOMINANT DEAFNESS; AUDITORY PATHWAY; SPIRAL GANGLION; MICE LACKING AB Human KCNQ4 mutations known as DFNA2 cause non-syndromic, autosomal-dominant, progressive high-frequency hearing loss in which the cellular and molecular basis is unclear. We provide immunofluorescence data showing that Kcnq4 expression in the adult cochlea has both longitudinal ( base to apex) and radial ( inner to outer hair cells) gradients. The most intense labeling is in outer hair cells at the apex and in inner hair cells as well as spiral ganglion neurons at the base. Spatiotemporal expression studies show increasing intensity of KCNQ4 protein labeling from postnatal day 21 (P21) to P120 mice that is most apparent in inner hair cells of the middle turn. We have identified four alternative splice variants of Kcnq4 in mice. The alternative use of exons 9-11 produces three transcript variants (v1-v3), whereas the fourth variant (v4) skips all three exons; all variants have the same amino acid sequence at the C termini. Both reverse transcription-PCR and quantitative PCR analyses demonstrate that these variants have differential expression patterns along the length of the mouse organ of Corti and spiral ganglion neurons. Our expression data suggest that the primary defect leading to high-frequency loss DFNA2 patients may be attributable to high levels of the dysfunctional Kcnq4_v3 variant in the spiral ganglion and inner hair cells in the basal hook region. Progressive hearing loss associated with aging may result from an increasing mutational load expansion toward the apex in inner hair cells and spiral ganglion neurons. C1 Creighton Univ, Sch Med, Dept Biomed Sci, Omaha, NE 68178 USA. Natl Inst Deafness & Other Commun Disorders, Sect Struct Cell Biol, NIH, Bethesda, MD 20892 USA. Univ Calif Davis, Ctr Neurosci, Dept Otolaryngol, Davis, CA 95616 USA. RP Beisel, KW (reprint author), Creighton Univ, Sch Med, Dept Biomed Sci, 2500 Calif Plaza, Omaha, NE 68178 USA. EM beisel@creighton.edu OI Fritzsch, Bernd/0000-0002-4882-8398 FU NIDCD NIH HHS [R01 DC004279, DC04279, DC07592, R01 DC005009, R01 DC05009] NR 50 TC 63 Z9 65 U1 0 U2 5 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD OCT 5 PY 2005 VL 25 IS 40 BP 9285 EP 9293 DI 10.1523/JNEUROSCI.2110-05.2005 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 971BD UT WOS:000232355200024 PM 16207888 ER PT J AU Longo, DL AF Longo, DL TI Radiation therapy in Hodgkin disease: Why risk a Pyrrhic victory? SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID BREAST-CANCER RISK; RADIOTHERAPY; CHEMOTHERAPY; METAANALYSIS; TRIALS C1 NIA, Baltimore, MD 21224 USA. RP Longo, DL (reprint author), NIA, 5600 Nathan Shock Dr,Box 9, Baltimore, MD 21224 USA. EM longod@grc.nia.nih.gov NR 9 TC 18 Z9 18 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD OCT 5 PY 2005 VL 97 IS 19 BP 1394 EP 1395 DI 10.1093/jnci/dji310 PG 2 WC Oncology SC Oncology GA 979NZ UT WOS:000232953400001 PM 16204683 ER PT J AU Allegra, CJ Childs, RW AF Allegra, CJ Childs, RW TI Cytotoxins and cancer immunotherapy: The dance of the Macabre? SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID HUMAN THYMIDYLATE SYNTHASE; P53; EXPRESSION; APOPTOSIS; ENZYME; TUMORS; CELLS C1 Network Med Commun & Res, N Potomac, MD 20878 USA. NHLBI, Hematol Branch, Bethesda, MD 20892 USA. RP Allegra, CJ (reprint author), Network Med Commun & Res, N Potomac, MD 20878 USA. EM callegra@nmcr.com; childsr@nih.gov NR 14 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD OCT 5 PY 2005 VL 97 IS 19 BP 1396 EP 1397 DI 10.1093/jnci/dji330 PG 2 WC Oncology SC Oncology GA 979NZ UT WOS:000232953400002 PM 16204684 ER PT J AU Edwards, BK Brown, ML Wingo, PA Howe, HL Ward, E Ries, LAG Schrag, D Jamison, PM Jemal, A Wu, XC Friedman, C Harlan, L Warren, J Anderson, RN Pickle, LW AF Edwards, BK Brown, ML Wingo, PA Howe, HL Ward, E Ries, LAG Schrag, D Jamison, PM Jemal, A Wu, XC Friedman, C Harlan, L Warren, J Anderson, RN Pickle, LW TI Annual report to the Nation on the status of cancer, 1975-2002, featuring population-based trends in cancer treatment SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Review ID STAGE BREAST-CANCER; CELL LUNG-CANCER; HEALTH MAINTENANCE ORGANIZATION; NONMETASTATIC PROSTATE-CANCER; ADJUVANT CHEMOTHERAPY USE; ADVANCED OVARIAN-CANCER; POSITIVE COLON-CANCER; SEER-MEDICARE DATA; CARCINOMA IN-SITU; QUALITY-OF-LIFE AB Background: The American Cancer Society (ACS), the Centers for Disease Control and Prevention (CDC), the National Cancer Institute (NCI), and the North American Association of Central Cancer Registries (NAACCR) collaborate annually to provide information on cancer rates and trends in the United States. This year's report updates statistics on the 15 most common cancers in the five major racial/ethnic populations in the United States for 1992-2002 and features population-based trends in cancer treatment. Methods: The NCI, the CDC, and the NAACCR provided information on cancer cases, and the CDC provided information on cancer deaths. Reported incidence and death rates were age-adjusted to the 2000 U.S. standard population, annual percent change in rates for fixed intervals was estimated by linear regression, and annual percent change in trends was estimated with join-point regression analysis. Population-based treatment data were derived from the Surveillance, Epidemiology, and End Results (SEER) Program registries, SEER-Medicare linked databases, and NCI Patterns of Care/Quality of Care studies. Results: Among men, the incidence rates for all cancer sites combined were stable from 1995 through 2002. Among women, the incidence rates increased by 0.3% annually from 1987 through 2002. Death rates in men and women combined decreased by 1.1% annually from 1993 through 2002 for all cancer sites combined and also for many of the 15 most common cancers. Among women, lung cancer death rates increased from 1995 through 2002, but lung cancer incidence rates stabilized from 1998 through 2002. Although results of cancer treatment studies suggest that much of contemporary cancer treatment for selected cancers is consistent with evidence-based guidelines, they also point to geographic, racial, economic, and age-related disparities in cancer treatment. Conclusions: Cancer death rates for all cancer sites combined and for many common cancers have declined at the same time as the dissemination of guideline-based treatment into the community has increased, although this progress is not shared equally across all racial and ethnic populations. Data from population-based cancer registries, supplemented by linkage with administrative databases, are an important resource for monitoring the quality of cancer treatment. Use of this cancer surveillance system, along with new developments in medical informatics and electronic medical records, may facilitate monitoring of the translation of basic science and clinical advances to cancer prevention, detection, and uniformly high quality of care in all areas and populations of the United States. C1 NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Div Canc Prevent & Control, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA USA. N Amer Assoc Cent Canc Registries, Springfield, IL USA. Amer Canc Soc, Epidemiol & Surveillance Res Dept, Atlanta, GA 30329 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Louisiana State Univ, Hlth Sci Ctr, New Orleans, LA USA. Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Div Vital Stats, Hyattsville, MD 20782 USA. RP Edwards, BK (reprint author), NCI, Div Canc Control & Populat Sci, 6116 Execut Blvd,Suite 504, Bethesda, MD 20892 USA. EM edwardsb@mail.nih.gov RI Ain, Kenneth/A-5179-2012 OI Ain, Kenneth/0000-0002-2668-934X NR 148 TC 635 Z9 656 U1 7 U2 74 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD OCT 5 PY 2005 VL 97 IS 19 BP 1407 EP 1427 DI 10.1093/jnci/dji289 PG 21 WC Oncology SC Oncology GA 979NZ UT WOS:000232953400008 PM 16204691 ER PT J AU Travis, LB Hill, D Dores, GM Gospodarowicz, M van Leeuwen, FE Holowaty, E Glimelius, B Andersson, M Pukkala, E Lynch, CF Pee, D Smith, SA Van't Veer, MB Joensuu, T Storm, H Stovall, M Boice, JD Gilbert, E Gail, MH AF Travis, LB Hill, D Dores, GM Gospodarowicz, M van Leeuwen, FE Holowaty, E Glimelius, B Andersson, M Pukkala, E Lynch, CF Pee, D Smith, SA Van't Veer, MB Joensuu, T Storm, H Stovall, M Boice, JD Gilbert, E Gail, MH TI Cumulative absolute breast cancer risk for young women treated for Hodgkin lymphoma SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID 2ND MALIGNANCY; BRCA2 MUTATION; NURSES HEALTH; DISEASE; AGE; CHILDHOOD; NEOPLASMS; CHEMOTHERAPY; THERAPY; COHORT AB Background: Many women develop breast cancer after treatment for Hodgkin lymphoma (HL) at a young age. We estimated this future risk, taking into account age and calendar year of HL diagnosis, HL treatment information, population breast cancer incidence rates, and competing causes of death. Methods: Relative risks of breast cancer for categories defined by radiation dose to the chest (0, 20-< 40 Gy, or >= 40 Gy) and use of alkylating agents (yes or no) were estimated from a case-control study conducted within an international population-based cohort of 3817 female 1-year survivors of HL diagnosed at age 30 years or younger from January 1, 1965, through December 31, 1994. To compute cumulative absolute risks of breast cancer, we used modified standardized incidence ratios to relate cohort breast cancer risks to those in the general population, enabling application of population-based breast cancer rates, and we allowed for competing risks by using population-based mortality rates in female HL survivors. Results: Cumulative absolute risks of breast cancer increased with age at end of follow-up, time since HL diagnosis, and radiation dose. For an HL survivor who was treated at age 25 years with a chest radiation dose of at least 40 Gy without alkylating agents, estimated cumulative absolute risks of breast cancer by age 35, 45, and 55 years were 1.4% (95% confidence interval [CI] = 0.9% to 2.1%), 11.1% (95% Cl = 7.4% to 16.3%), and 29.0% (95% CI = 20.2% to 40.1%), respectively. Cumulative absolute risks were lower in women treated with alkylating agents. Conclusions: Breast cancer projections varied considerably by type of HL therapy, time since HL diagnosis, and age at end of follow-up. These estimates are applicable to HL survivors treated with regimens of the past and can be used to counsel such patients and plan management and preventive strategies. Projections should be used with caution, however, in patients treated with more recent approaches, including limited-field radiotherapy and/or ovary-sparing chemotherapy. C1 NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. NCI, Div Canc Prevent, NIH, DHHS, Bethesda, MD 20892 USA. Univ Toronto, Princess Margaret Hosp, Toronto, ON, Canada. Netherlands Canc Inst, Amsterdam, Netherlands. Canc Care Ontario, Toronto, ON, Canada. Univ Uppsala, Uppsala, Sweden. Danish Canc Soc, Copenhagen, Denmark. Finnish Canc Registry, FIN-00170 Helsinki, Finland. Univ Iowa, Iowa City, IA USA. Informat Management Serv Inc, Rockville, MD USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Dr Daniel Den Hoed Canc Ctr, NL-3008 AE Rotterdam, Netherlands. Univ Helsinki, Cent Hosp, Helsinki, Finland. Int Epidemiol Inst, Rockville, MD USA. Vanderbilt Univ, Ctr Canc, Nashville, TN USA. RP Travis, LB (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, DHHS, EPS 7086, Bethesda, MD 20892 USA. EM travisl@mail.nih.gov OI Storm, Hans/0000-0001-7223-8198 FU Intramural NIH HHS NR 42 TC 213 Z9 216 U1 0 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD OCT 5 PY 2005 VL 97 IS 19 BP 1428 EP 1437 DI 10.1093/jnci/dji290 PG 10 WC Oncology SC Oncology GA 979NZ UT WOS:000232953400009 PM 16204692 ER PT J AU Kornblatt, JA Schuck, P AF Kornblatt, JA Schuck, P TI Influence of temperature on the conformation of canine plasminogen: An analytical ultracentrifugation and dynamic light scattering study SO BIOCHEMISTRY LA English DT Article ID SEDIMENTATION COEFFICIENT DISTRIBUTIONS; ANTIFIBRINOLYTIC AMINO-ACIDS; PROTEIN-PROTEIN INTERACTIONS; SIZE-DISTRIBUTION ANALYSIS; GLU-PLASMINOGEN; LAMM EQUATION; ALLOSTERIC REGULATION; VELOCITY ANALYSIS; WATER; HEMOGLOBIN AB Plasminogen is known to undergo an extremely large conformational change when it binds ligands; the two well-established conformations are either closed (absence of external ligand) or open (presence of external ligand). We show here that plasminogen is more complicated than can be accommodated by a two-state, closed/open, model. Temperature changes induce large structural changes which can be detected with either dynamic light scattering or analytical ultracentrifugation. The temperatureinduced changes are not related to the classical closed/open conformational change since both closed and open forms of the protein are similarly influenced. It appears as though the packing density of the protein increases as the temperature is raised. Over the range 4-20 degrees C, the Stokes' radius of the classical closed plasminogen goes from 4.7 to 4.2 nm, and that of the classical open form goes from 5.55 to 5.0 nm. These changes in packing can be rationalized if temperature change induces a large conformational change and if this is accompanied by a large change in hydration, by a change in solute binding, or by a change in the total void volume of the protein. C1 Concordia Univ, Dept Biol, Enzyme Res Grp, Montreal, PQ H4B 1R6, Canada. NIH, Bethesda, MD 20892 USA. RP Kornblatt, JA (reprint author), Concordia Univ, Dept Biol, Enzyme Res Grp, 7141 Sherbrooke Ouest, Montreal, PQ H4B 1R6, Canada. EM krnbltt@vax2.concordia.ca OI kornblatt, jack/0000-0002-9802-8321; Schuck, Peter/0000-0002-8859-6966 FU Intramural NIH HHS NR 43 TC 11 Z9 11 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD OCT 4 PY 2005 VL 44 IS 39 BP 13122 EP 13131 DI 10.1021/bi050895y PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 969RZ UT WOS:000232253700021 PM 16185080 ER PT J AU Ruttmann, E Brant, LJ Concin, H Diem, G Rapp, K Ulmer, H AF Ruttmann, E Brant, LJ Concin, H Diem, G Rapp, K Ulmer, H CA Voralberg Hlth Monitoring Promotio TI gamma-glutamyltransferase as a risk factor for cardiovascular disease mortality - An epidemiological investigation in a cohort of 163,944 Austrian adults SO CIRCULATION LA English DT Article DE arteriosclerosis; cardiovascular diseases; prevention; risk factors; gamma-glutamyltransferase ID MODERATE ALCOHOL-CONSUMPTION; CORONARY-HEART-DISEASE; MYOCARDIAL-INFARCTION; TRANSPEPTIDASE; POPULATION; ASSOCIATION; STROKE; MEN; OXIDATION; DRINKING AB Background-There is evidence from recent studies that gamma-glutamyltransferase (GGT) is likely to be associated with cardiovascular disease (CVD). However, few studies to date with sufficient sample size and follow-up investigated the association of GGT with CVD mortality. Methods and Results-The relation of GGT to the risk of death from CVD was examined in a cohort of 163 944 Austrian adults that was monitored for up to 17 years. To evaluate GGT as an independent predictor, Cox proportional hazards models were calculated, which adjusted for established risk factors. In both men and women, high GGT was significantly ( P < 0.001) associated with total mortality from CVD, showing a clear dose-response relationship. Adjusted hazard ratios ( 95% CI) per log GGT increase were 1.66 ( 1.40 to 1.98) in men and 1.64 (1.36 to 1.97) in women. In men, subgroup analyses showed that high GGT was positively associated with incident fatal events of chronic forms of coronary heart disease ( P = 0.009), congestive heart failure ( P < 0.001), and hemorrhagic ( P = 0.01) and ischemic stroke ( P < 0.001). No significant associations were observed for acute myocardial infarction ( P = 0.16). In women, hazard ratios suggested associations in all subgroups; however, for hemorrhagic and ischemic stroke they were not statistically significant ( P = 0.09 and P = 0.07, respectively). In addition, subgroup analyses stratified by age revealed a stronger relationship of GGT in younger participants. Hazard ratios for total CVD were 2.03 (1.53 to 2.69) in men and 2.60 ( 1.53 to 4.42) in women younger than 60 years. Conclusions-This study demonstrates in a large, prospectively observed cohort that GGT is independently associated with cardiovascular mortality. C1 Innsbruck Med Univ, Dept Med Stat Informat & Hlth Econ, A-6020 Innsbruck, Austria. NIA, Ctr Gerontol Res, Baltimore, MD 21224 USA. Agcy Prevent & Social Med, Bregenz, Austria. Univ Ulm, Dept Epidemiol, Ulm, Germany. RP Ulmer, H (reprint author), Innsbruck Med Univ, Dept Med Stat Informat & Hlth Econ, Schoepfstr 41, A-6020 Innsbruck, Austria. EM hanno.ulmer@uibk.ac.at RI Ruttmann, Elfriede/D-6501-2011; vhmpp, aks/F-9756-2012; Ulmer, Hanno/C-3488-2011 OI Ulmer, Hanno/0000-0001-5911-1002 NR 35 TC 302 Z9 322 U1 1 U2 12 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 4 PY 2005 VL 112 IS 14 BP 2130 EP 2137 DI 10.1161/CIRCULATIONAHA.105.552547 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 970ET UT WOS:000232288700010 PM 16186419 ER PT J AU Nabel, EG AF Nabel, EG TI Notes from the director National Heart, Lung, and Blood Institute - Fostering the independence of new investigators SO CIRCULATION LA English DT Article DE circulation; trials; research C1 NHLBI, NIH, Bethesda, MD 20892 USA. RP Nabel, EG (reprint author), NHLBI, NIH, Bldg 31,Rm 5A52,31 Ctr Dr,MSC 2486, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 4 PY 2005 VL 112 IS 14 BP 2217 EP 2218 DI 10.1161/CIRCULATIONHA.105.581850 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 970ET UT WOS:000232288700021 PM 16203932 ER PT J AU Ye, YH Shibata, Y Kikkert, M van Voorden, S Wiertz, E Rapoport, TA AF Ye, YH Shibata, Y Kikkert, M van Voorden, S Wiertz, E Rapoport, TA TI Recruitment of the p97 ATPase and ubiquitin ligases to the site of retrotranslocation at the endoplasmic reticulum membrane SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE AAA ATPase; ER-associated degradation; dislocation; Derlin; Hrd1 ID MOTILITY FACTOR-RECEPTOR; RETRO-TRANSLOCATION; MISFOLDED PROTEINS; DEGRADATION; ER; CYTOSOL; GP78; RECOGNITION; POLYPEPTIDE; DISLOCATION AB Misfolded proteins are eliminated from the endoplasmic reticulum (ER) by retrotranslocation into the cytosol, a pathway hijacked by certain viruses to destroy MHC class I heavy chains. The translocation of polypeptides across the ER membrane requires their polyubiquitination and subsequent extraction from the membrane by the p97 ATPase [also called valosin-containing protein (VCP) or, in yeast, Cdc48]. In higher eukaryotes, p97 is bound to the ER membrane by a membrane protein complex containing Derlin-1 and VCP-interacting membrane protein (VIMP). How the ubiquitination machinery is recruited to the p97/Derlin/VIMP complex is unclear. Here, we report that p97 interacts directly with several ubiquitin ligases and facilitates their recruitment to Derlin-1. During retrotranslocation, a substrate first interacts with Derlin-1 before p97 and other factors join the complex. These data, together with the fact that Derlin-1 is a multispanning membrane protein forming homo-oligomers, support the idea that Derlin-1 is part of a retrotranslocation channel that is associated with both the polyubiquitination and p97-ATPase machineries. C1 Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Leiden Univ, Med Ctr, Dept Med Microbiol, NL-2300 RC Leiden, Netherlands. RP Rapoport, TA (reprint author), Harvard Univ, Sch Med, Howard Hughes Med Inst, 240 Longwood Ave, Boston, MA 02115 USA. EM tom_rapoport@hms.harvard.edu FU NIGMS NIH HHS [R01 GM05586-10] NR 28 TC 212 Z9 220 U1 2 U2 11 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 4 PY 2005 VL 102 IS 40 BP 14132 EP 14138 DI 10.1073/pnas.0505006102 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 971OD UT WOS:000232392900004 PM 16186510 ER PT J AU Laricchia-Robbio, L Tamura, T Karpova, T Sprague, BL McNally, JG Ozato, K AF Laricchia-Robbio, L Tamura, T Karpova, T Sprague, BL McNally, JG Ozato, K TI Partner-regulated interaction of IFN regulatory factor 8 with chromatin visualized in live macrophages SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE real-time mobility; transcription factor; fluorescence recovery after photobleaching ID SEQUENCE-BINDING-PROTEIN; MYELOID PROGENITOR CELLS; LIVING HUMAN-CELLS; IN-VIVO; RAPID EXCHANGE; FLUORESCENCE COMPLEMENTATION; GLUCOCORTICOID-RECEPTOR; PU.1; TRANSCRIPTION; ICSBP/IRF-8 AB IFN regulatory factor (IRF) 8 is a transcription factor that directs macrophage differentiation. By fluorescence recovery after photobleaching, we visualized the movement of IRF8-GFP in differentiating macrophages. Recovery data fitted to mathematical models revealed two binding states for IRF8. The majority of IRF8 was highly mobile and transiently interacted with chromatin, whereas a small fraction of IRF8 bound to chromatin more stably. IRF8 mutants that did not stimulate macrophage differentiation showed a faster recovery, revealing little interaction with chromatin. A macrophage activation signal by IFN-gamma/LPS led to a global slowdown of IRF8 movement, leading to increased chromatin binding. In fibroblasts where IRF8 has no known function, WT IRF8 moved as fast as the mutants, indicating that IRF8 does not interact with chromatin in these cells. However, upon introduction of IRF8 binding partners, PU.1 and/or IRF1, the mobility of IRF8 was markedly reduced, producing a more stably bound component. Together, IRF8-chromatin interaction is dynamic in live macrophages and influenced by partner proteins and immunological stimuli. C1 NICHHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA. RP Laricchia-Robbio, L (reprint author), NICHHD, Lab Mol Growth Regulat, NIH, Bethesda, MD 20892 USA. EM ozatok@mail.nih.gov RI Sprague, Brian/A-8923-2009 FU Intramural NIH HHS NR 39 TC 32 Z9 32 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 4 PY 2005 VL 102 IS 40 BP 14368 EP 14373 DI 10.1073/pnas.0504014102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 971OD UT WOS:000232392900045 PM 16183743 ER PT J AU Gattinoni, L Finkelstein, SE Klebanoff, CA Antony, PA Palmer, DC Spiess, PJ Hwang, LN Yu, ZY Wrzesinski, C Heimann, DM Surh, CD Rosenberg, SA Restifo, NP AF Gattinoni, L Finkelstein, SE Klebanoff, CA Antony, PA Palmer, DC Spiess, PJ Hwang, LN Yu, ZY Wrzesinski, C Heimann, DM Surh, CD Rosenberg, SA Restifo, NP TI Removal of homeostatic cytokine sinks by lymphodepletion enhances the efficacy of adoptively transferred tumor-specific CD8(+) T cells SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID NATURAL-KILLER-CELLS; IN-VIVO; CUTTING EDGE; PROLIFERATION; NAIVE; IMMUNOTHERAPY; AUTOIMMUNITY; PHENOTYPE; SURVIVAL; IMMUNITY AB Depletion of immune elements before adoptive cell transfer (ACT) can dramatically improve the antitumor efficacy of transferred CD8(+) T cells, but the specific mechanisms that contribute to this enhanced immunity remain poorly defined. Elimination of CD4(+) CD25(+) regulatory T (T reg) cells has been proposed as a key mechanism by which lymphodepletion augments ACT-based immunotherapy. We found that even in the genetic absence of T reg cells, a nonmyeloablative regimen substantially augmented CD8(+) T cell reactivity to self-tissue and tumor. Surprisingly, enhanced antitumor efficacy and autoimmunity was caused by increased function rather than increased numbers of tumor-reactive T cells, as would be expected by homeostatic mechanisms. The gamma(C) cytokines IL-7 and IL-15 were required for augmenting T cell functionality and antitumor activity. Removal of gamma(C) cytokine-responsive endogenous cells using antibody or genetic means resulted in the enhanced antitumor responses similar to those seen after nonmyeloablative conditioning. These data indicate that lymphodepletion removes endogenous cellular elements that act as sinks for cytokines that are capable of augmenting the activity of self/tumor-reactive CD8(+) T cells. Thus, the restricted availability of homeostatic cytokines can be a contributing factor to peripheral tolerance, as well as a limiting resource for the effectiveness of tumor-specific T cells. C1 NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NIH, Howard Hughes Med Inst, Res Scholars Program, Bethesda, MD 20814 USA. Scripps Res Inst, Dept Immunol, La Jolla, CA 92037 USA. RP Restifo, NP (reprint author), NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM restifo@nih.gov RI Gattinoni, Luca/A-2281-2008; Wrzesinski, Claudia/A-3077-2008; Restifo, Nicholas/A-5713-2008; Klebanoff, Christopher/B-8088-2008; Palmer, Douglas/B-9454-2008; Klebanoff, Christopher/D-9581-2011; OI Gattinoni, Luca/0000-0003-2239-3282; Palmer, Douglas/0000-0001-5018-5734; Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [Z01 BC010763-01, Z01 SC003811-32, Z99 CA999999] NR 29 TC 472 Z9 488 U1 3 U2 10 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD OCT 3 PY 2005 VL 202 IS 7 BP 907 EP 912 DI 10.1084/jem.20050732 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 974VH UT WOS:000232619000005 PM 16203864 ER PT J AU Bryceson, YT March, ME Barber, DF Ljunggren, HG Long, EO AF Bryceson, YT March, ME Barber, DF Ljunggren, HG Long, EO TI Cytolytic granule polarization and degranulation controlled by different receptors in resting NK cells SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID NATURAL-KILLER-CELLS; CYTOTOXIC T-LYMPHOCYTES; LEUKOCYTE ADHESION; FC-RECEPTORS; CELLULAR CYTOTOXICITY; SIGNAL-TRANSDUCTION; AVIDITY REGULATION; MHC MOLECULES; INTEGRINS; RECOGNITION AB The relative contribution to cytotoxicity of each of the multiple NK cell activation receptors has been difficult to assess. Using Drosophila insect cells, which express ligands of human NK cell receptors, we show that target cell lysis by resting NK cells is controlled by different receptor signals for cytolytic granule polarization and degranulation. Intercellular adhesion molecule ( ICAM)-1 on insect cells was sufficient to induce polarization of granules, but not degranulation, in resting NK cells. Conversely, engagement of the Fc receptor CD16 by rabbit IgG on insect cells induced degranulation without specific polarization. Lysis by resting NK cells occurred when polarization and degranulation were induced by the combined presence of ICAM-1 and IgG on insect cells. Engagement of receptor 2B4 by CD48 on insect cells induced weak polarization and no degranulation. However, coengagement of 2B4 and CD16 by their respective ligands resulted in granule polarization and cytotoxicity in the absence of leukocyte functional antigen-1-mediated adhesion to target cells. These data show that cytotoxicity by resting NK cells is controlled tightly by separate or cooperative signals from different receptors for granule polarization and degranulation. C1 NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. Huddinge Univ Hosp, Ctr Infect Med, Karolinska Inst, Dept Med, S-14186 Stockholm, Sweden. RP Long, EO (reprint author), Ctr Nacl Biotecnol, Carreterra Colmenar KM 16, E-28049 Madrid, Spain. EM eLong@niaid.nih.gov RI Barber, Domingo/G-1257-2010; Long, Eric/G-5475-2011; OI Barber, Domingo/0000-0001-8824-5405; Long, Eric/0000-0002-7793-3728; Bryceson, Yenan/0000-0002-7783-9934 FU Intramural NIH HHS NR 54 TC 244 Z9 248 U1 0 U2 4 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD OCT 3 PY 2005 VL 202 IS 7 BP 1001 EP 1012 DI 10.1084/jem.20051143 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 974VH UT WOS:000232619000014 PM 16203869 ER PT J AU Rao, JS Langenbach, R Bosetti, F AF Rao, JS Langenbach, R Bosetti, F TI Down-regulation of brain nuclear factor-kappa B pathway in the cyclooxygenase-2 knockout mouse SO MOLECULAR BRAIN RESEARCH LA English DT Article DE NF-kappa B; p65; phospho p65; p50; phospho I-kappa B alpha; COX-2 KO ID TUMOR-NECROSIS-FACTOR; DNA-BINDING ACTIVITY; TRANSCRIPTION FACTOR; GENE-EXPRESSION; INTRACELLULAR CALCIUM; SIGNALING PATHWAYS; PHOSPHOLIPASE A(2); RAT-BRAIN; ACTIVATION; CELLS AB Cyclooxygenase (COX) is the rate-limiting enzyme in the synthesis of Prostaglandins (PGs) from arachidonic acid. Evidence suggests that neuronal COX-2 gene expression is mainly regulated by the transcription factor nuclear factor kappa-B (NF-kappa B). The present study was undertaken to determine whether there is a shared regulation of NF-kappa B or of nuclear factor of activated T-cells cytoplasmic (NFATc) with COX-2 and whether these transcription factors known to regulate COX-2 expression are altered in brain from COX-2 knockout (COX-2(-/-)) mice compared to wild type. We found a decrease in NF-kappa B DNA-protein binding activity, which was accompanied by a reduction of the phosphorylation state of both I-kappa B alpha and p65 proteins in the COX-2(-/-) mice. The mRNA and protein levels of p65 were also reduced in COX-2(-/-) mice, whereas total cytoplasmic I-kappa B protein level was not significantly changed. Taken together, these changes may be responsible for the observed decrease in NF-kappa B DNA binding activity. NF-kappa B DNA binding activity was selectively affected in the COX-2(-/-) mice compared to the wild type as there was no significant change in NFATc DNA binding activity. Overall, our data indicate that constitutive brain NF-kappa B activity is decreased in COX-2 deficient mice and suggest a reciprocal coupling between NF-kappa B and COX-2. Published by Elsevier B.V. C1 NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. NIEHS, Lab Expt Carcinogenesis & Mutagenesis, Res Triangle Pk, NC 27709 USA. RP Rao, JS (reprint author), NIA, Brain Physiol & Metab Sect, NIH, 9000 Rockville Pike,Bldg 9,Room 1S 128, Bethesda, MD 20892 USA. EM jrao@mail.nih.gov RI Rao, Jagadeesh/C-1250-2009 NR 50 TC 6 Z9 6 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD OCT 3 PY 2005 VL 139 IS 2 BP 217 EP 224 DI 10.1016/j.molbrainres.2005.05.008 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 973IF UT WOS:000232515400004 ER PT J AU Salvatore, MF Fisher, B Surgener, SP Gerhardt, GA Rouault, T AF Salvatore, MF Fisher, B Surgener, SP Gerhardt, GA Rouault, T TI Neurochemical investigations of dopamine neuronal systems in iron-regulatory protein 2 (IRP-2) knockout mice SO MOLECULAR BRAIN RESEARCH LA English DT Article DE dopamine; IRP-2; iron metabolism; striatum; tyrosine hydroxylase ID TYROSINE-HYDROXYLASE PHOSPHORYLATION; PARKINSONS-DISEASE; SUBSTANTIA-NIGRA; NEUROTROPHIC FACTOR; FISCHER-344 RATS; IN-VIVO; METABOLISM; NEUROMELANIN; MONKEYS; BRAIN AB Abnormal iron accumulations are frequently observed in the brains of patients with Parkinson's disease and in normal aging. Iron metabolism is regulated in the CNS by iron regulatory proteins (IRP-1 and IRP-2). Mice engineered to lack IRP-2 develop abnormal motoric behaviors including tremors at rest, abnormal gait, and bradykinesia at middle to late age (18 to 24 months). To further characterize the dopamine (DA) systems of IRP-2 -/- mice, we harvested CNS tissue from age-matched wild type and IRP-2 -/- (16-19 months) and analyzed the protein levels of tyrosine hydroxylase (TH), dopamine transporter (DAT), vesicular monoamine transporter (VMAT2), and DA levels in dorsal striatum, ventral striatum (including the core and shell of nucleus accumbens), and midbrain. We further analyzed the phosphorylation of TH in striatum at serine 40, serine 3 1, and serine 19. In both dorsal and ventral striatum of IRP-2 knockout mice, there was a 20-25% loss of TH protein and accompanied by a similar to 50% increase in serine 40 phosphorylation above wild-type levels. No change in serine 31 phosphorylation was observed. In the ventral striatum, there was also a significant loss (similar to 40%) of DAT and VMAT2. Levels of DA were decreased (similar to 20%) in dorsal striatum, but turnover of DA was also elevated (similar to 30%) in dorsal striatum of IRP-2 -/- mice. We conclude that iron misregulation associated with the loss of IRP-2 protein affects DA regulation in the striatum. However, the modest loss of DA and DA-regulating proteins does not reflect the pathology of PD or animal models of PD. Instead, these observations support that the IRP-2 -/- genotype may enable neurobiological events associated with aging. (c) 2005 Elsevier B.V. All rights reserved. C1 Univ Kentucky, Med Ctr, Dept Anat & Neurobiol, Morris K Udall Parkinsons Dis Res Ctr Excellence, Lexington, KY 40536 USA. NICHHD, Cell Biol & Metab Branch, Sect Human Iron Metab, Bethesda, MD 20892 USA. RP Salvatore, MF (reprint author), Univ Kentucky, Med Ctr, Dept Anat & Neurobiol, Morris K Udall Parkinsons Dis Res Ctr Excellence, 306 Whitney Hendrickson Bldg,800 Rose St, Lexington, KY 40536 USA. EM msalv2@uky.edu NR 34 TC 21 Z9 22 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-328X J9 MOL BRAIN RES JI Mol. Brain Res. PD OCT 3 PY 2005 VL 139 IS 2 BP 341 EP 347 DI 10.1016/j.molbrainres.2005.06.002 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 973IF UT WOS:000232515400017 ER PT J AU Sigurdson, AJ Hauptmann, M Alexander, BH Doody, MM Thomas, CB Struewing, JP Jones, IM AF Sigurdson, AJ Hauptmann, M Alexander, BH Doody, MM Thomas, CB Struewing, JP Jones, IM TI DNA damage among thyroid cancer and multiple cancer cases, controls, and long-lived individuals SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS LA English DT Article DE comet assay; multiple cancers; genetic variation; risk factors; hyper-normal controls ID COMET ASSAY; BREAST-CANCER; REPAIR; SUSCEPTIBILITY; ASSOCIATION; INSTABILITY; HUMANS; CELLS AB Variation in the detection, signaling, and repair of DNA damage contributes to human cancer risk. To assess capacity to modulate endogenous DNA damage among radiologic technologists who had been diagnosed with breast cancer and another malignancy (breast-other, n = 42), early-onset breast cancer (early-onset, age <= 35; n = 38), thyroid cancer (n = 69), long-lived cancer-free individuals (hyper-normals, n = 20) and cancer-free controls (n = 49) we quantified DNA damage (single strand breaks and abasic sites) in untreated lymphoblastoid cell lines using the alkaline comet assay. Komet (TM) software provided comet tail length, % DNA in tail (tail DNA), comet distributed moment (CDM), and Olive tail moment (OTM) summarized as the geometric mean of 100 cells. Category cut-points (median and 75th percentile) were determined from the distribution among controls. Tail length (for >= 75% versus below the median, age-adjusted) was most consistently associated with the highest odds ratios in the breast-other, early-onset, and thyroid cancer groups (with risk increased 10-, 5- or 19-fold, respectively, with wide confidence intervals) and decreased risk among the hyper-normal group. For the other three comet measures, risk of breast-other was elevated approximately three-fold. Risk of early-onset breast cancer was mixed and risk of thyroid cancer ranged from null to a two-fold increase. The hyper-normal group showed decreased odds ratios for tail DNA and OTM, but not CDM. DNA damage, as estimated by all comet measures, was relatively unaffected by survival time, reproductive factors, and prior radiation treatment. We detected a continuum of endogenous DNA damage that was highest among cancer cases, less in controls, and suggestively lowest in hyper-normal individuals. Measuring this DNA damage phenotype may contribute to the identification of susceptible sub-groups. Our observations require replication in a prospective study with a large number of pre-diagnostic samples. (c) 2005 Elsevier B.V. All rights reserved. C1 NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA. NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA. Univ Minnesota, Div Environm & Occupat Hlth, Minneapolis, MN 55455 USA. Lawrence Livermore Natl Lab, Livermore, CA 94551 USA. NCI, Lab Populat Genet, Canc Res Ctr, NIH,DHHS, Bethesda, MD 20892 USA. RP Sigurdson, AJ (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, 6120 Execut Blvd,EPS 7092,MSC 7238, Bethesda, MD 20892 USA. EM sigurdsa@mail.nih.gov; hauptmam@mail.nih.gov; balex@umn.edu; doodym@mail.nih.gov; thomas5@llnl.gov; struewij@mail.nih.gov; jones20@llnl.gov RI Struewing, Jeffery/C-3221-2008; Struewing, Jeffery/I-7502-2013 OI Struewing, Jeffery/0000-0002-4848-3334 FU NCI NIH HHS [N01-CP-15673, N01-CP-51016, N02-CP-81005, N02-CP-81121] NR 25 TC 27 Z9 30 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1383-5718 J9 MUTAT RES-GEN TOX EN JI Mutat. Res. Genet. Toxicol. Environ. Mutagen. PD OCT 3 PY 2005 VL 586 IS 2 BP 173 EP 188 DI 10.1016/j.mrgentox.2005.07.001 PG 16 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 966CB UT WOS:000231996100008 PM 16099702 ER PT J AU Miller, FG Brody, H AF Miller, FG Brody, H TI Viewpoint: Professional integrity in industry-sponsored clinical trials SO ACADEMIC MEDICINE LA English DT Article ID CONFLICTS-OF-INTEREST; PHARMACEUTICAL-INDUSTRY; ANTIINFLAMMATORY DRUGS; BIOMEDICAL-RESEARCH; INTERNAL MORALITY; MEDICINE; REGISTRATION; PERSPECTIVE; ARTICLES; QUALITY AB Evidence-based medicine (EBM) relies on accurate data derived from well-designed, clinically relevant randomized controlled trials (RCTs). Most randomized trials, however, are conducted by industry sponsors aiming at licensing and marketing drugs, which may weaken the usefulness of the findings to EBM. Disturbing evidence has emerged of widespread biases in industry-sponsored trials, including publication bias, selective reporting of findings, and distorted interpretation of results. These practices compromise the professional integrity of physician-investigators who contribute to them. In turn, the well-being of patients participating in RCTs may be jeopardized, and the evidence base upon which EBM is practiced may be corrupted. Regulatory reform alone will be inadequate to resolve these problems,attention must also be paid to physicians' professionalism. The authors recommend a change in the culture of academic medicine whereby physician-investigators who maintain professional integrity are rewarded or recognized. Educational interventions promoting integrity in clinical research may be one part of affecting such change. C1 NIH, Dept Clin Bioeth, Unit Clin Res, Bethesda, MD 20892 USA. Michigan State Univ, Ctr Eth & Humanities Life Sci, Dept Family Practice, E Lansing, MI USA. Michigan State Univ, Ctr Eth & Humanities Life Sci, Dept Philosophy, E Lansing, MI USA. RP Miller, FG (reprint author), NIH, Dept Clin Bioeth, Unit Clin Res, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM fmiller@nih.gov NR 39 TC 17 Z9 17 U1 1 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD OCT PY 2005 VL 80 IS 10 BP 899 EP 904 DI 10.1097/00001888-200510000-00005 PG 6 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 968PL UT WOS:000232174400004 PM 16186605 ER PT J AU DiMattia, M Govindasamy, L Levy, HC Gurda-Whitaker, B Kalina, A Kohlbrenner, E Chiorini, JA McKenna, R Muzyczka, N Zolotukhin, S Agbandje-Mckenna, M AF DiMattia, M Govindasamy, L Levy, HC Gurda-Whitaker, B Kalina, A Kohlbrenner, E Chiorini, JA McKenna, R Muzyczka, N Zolotukhin, S Agbandje-Mckenna, M TI Production, purification, crystallization and preliminary X-ray structural studies of adeno-associated virus serotype 5 SO ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY AND CRYSTALLIZATION COMMUNICATIONS LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; HUMAN GENE-THERAPY; MOLECULAR REPLACEMENT; SIALIC-ACID; VECTORS; TYPE-2; BINDING; TRANSDUCTION; PROTEIN; IDENTIFICATION C1 Univ Florida, Ctr Struct Biol, McKnight Brain Inst, Dept Biochem & Mol Biol, Gainesville, FL 32610 USA. Univ Florida, Div Cell & Mol Therapy, Gainesville, FL 32610 USA. NIDCR, GTTB, NIH, Bethesda, MD 20892 USA. Univ Florida, Coll Med, Dept Mol Genet & Microbiol, Gainesville, FL 32610 USA. Univ Florida, Coll Med, Powell Gene Therapy Ctr, Gainesville, FL 32610 USA. RP Agbandje-Mckenna, M (reprint author), Univ Florida, Ctr Struct Biol, McKnight Brain Inst, Dept Biochem & Mol Biol, Gainesville, FL 32610 USA. EM mckenna@ufl.edu OI Gurda, Brittney /0000-0002-0174-9385 FU NCRR NIH HHS [RR-01646, P41 RR001646]; NHLBI NIH HHS [P01 HL051811, P01 HL59412, P01 HL059412, P01 HL51811]; NIGMS NIH HHS [DMR0225180] NR 25 TC 27 Z9 28 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1744-3091 J9 ACTA CRYSTALLOGR F JI Acta Crystallogr. F-Struct. Biol. Cryst. Commun. PD OCT PY 2005 VL 61 BP 917 EP 921 DI 10.1107/S1744309105028514 PN 10 PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA 971AU UT WOS:000232354300014 PM 16511195 ER PT J AU Schoolwerth, AC Engelgau, MM Hostetter, TH AF Schoolwerth, AC Engelgau, MM Hostetter, TH TI A public health action plan is needed for chronic kidney disease SO ADVANCES IN CHRONIC KIDNEY DISEASE LA English DT Article DE kidney disease; public health; surveillance; prevention; outcomes; end-stage renal disease ID STAGE RENAL-DISEASE; URINARY ALBUMIN EXCRETION; DIABETIC NEPHROPATHY; UNITED-STATES; CARDIOVASCULAR OUTCOMES; CONTROLLED-TRIAL; US POPULATION; PROGRESSION; RISK; MICROALBUMINURIA AB In 2005, chronic kidney disease (CKD) meets all criteria for classification as a public health problem in the United States. It imposes a large burden on society that is increasing despite ongoing efforts to control the disease. The burden is unevenly distributed by race and economic status, whereas evidence suggests that preventive strategies could substantially reduce the burden. Finally, there are indications that such strategies are not yet in place. A broad and coordinated public health approach to the burgeoning health, economic, and societal challenges of CKD is needed to complement present clinical approaches, increase awareness, promote early detection, and facilitate prevention and treatment. (c) 2005 by the National Kidney Foundation, Inc. C1 Ctr Dis Control & Prevent, Div Diabet Translat, Atlanta, GA USA. Dartmouth Coll Sch Med, Sect Hypertens & Nephrol, Hanover, NH USA. NIDDKD, Natl Kidney Dis Educ Program, NIH, Bethesda, MD USA. RP Schoolwerth, AC (reprint author), 1 Med Ctr Dr,2M, Lebanon, NH 03756 USA. EM anton.c.schoolwerth@hitchcock.org NR 49 TC 16 Z9 16 U1 1 U2 4 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1548-5595 J9 ADV CHRONIC KIDNEY D JI Adv. Chronic Kidney Dis. PD OCT PY 2005 VL 12 IS 4 BP 418 EP 423 DI 10.1053/a.ackd.2005.07.012 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 974YJ UT WOS:000232627000012 PM 16198282 ER PT J AU Cargill, VA AF Cargill, VA TI HIV/hepatitis C virus co-infection: its human face SO AIDS LA English DT Editorial Material ID CHRONIC HEPATITIS-C; RIBAVIRIN C1 NIH, DHHS, Off AIDS Res, Bethesda, MD 20892 USA. RP Cargill, VA (reprint author), NIH, DHHS, Off AIDS Res, Bethesda, MD 20892 USA. NR 4 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0269-9370 J9 AIDS JI Aids PD OCT PY 2005 VL 19 SU 3 BP S1 EP S2 DI 10.1097/01.aids.0000192062.63539.98 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 988DF UT WOS:000233570900001 PM 16251804 ER PT J AU Joseph, J Stoff, DA van der Horst, C AF Joseph, J Stoff, DA van der Horst, C TI HIV/hepatitis C virus co-infection: basic, behavioral and clinical research in mental health and drug abuse SO AIDS LA English DT Editorial Material C1 NIMH, Ctr Mental Hlth Res AIDS, Bethesda, MD 20892 USA. Univ N Carolina, Ctr AIDS Res, Chapel Hill, NC USA. RP Joseph, J (reprint author), NIMH, Ctr Mental Hlth Res AIDS, Room 6202,MSC 9619,6001 Execut Blvd, Bethesda, MD 20892 USA. EM jjeymoha@mail.nih.gov FU NIAID NIH HHS [AI25868, P30-AI50410]; PHS HHS [5U 19A1053217] NR 0 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0269-9370 J9 AIDS JI Aids PD OCT PY 2005 VL 19 SU 3 BP S3 EP S7 DI 10.1097/01.aids.0000192063.01658.48 PG 5 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 988DF UT WOS:000233570900002 PM 16251825 ER PT J AU Kresina, TF Eldred, L Bruce, RD Francis, H AF Kresina, TF Eldred, L Bruce, RD Francis, H TI Integration of pharmacotherapy for opioid addiction into HIV primary care for HIV/hepatitis C virus-co-infected patients SO AIDS LA English DT Article; Proceedings Paper CT Symposium on HIV/Hepatitis C Co-Infection - Impact on Nervous System Disease Burden CY OCT 02-03, 2003 CL Bethesda, MD SP NIH DE substance abuse treatment; HIV primary care; buprenorphine; HIV/HCV co-infection ID INJECTION-DRUG USERS; ACTIVE ANTIRETROVIRAL THERAPY; HEPATITIS-C; DEPENDENT PATIENTS; BUPRENORPHINE; NALTREXONE; MAINTENANCE; SUBSTANCE; NALOXONE; BEHAVIOR AB Pharmacotherapy for substance abuse is a rapidly evolving field comprising both old and new effective treatments for substance use. Opiate agonist therapy has been shown to diminish and often eliminate opiate use. This behavior change has resulted in the reduced transmission of many infections, including HIV, hepatitis C virus (HCV), and an enhanced quality of life. For the past 35 years, the provision of opioid agonist therapy has been limited to opioid treatment programmes. Opioid treatment programmes treat approximately 200 000 of the estimated million opiate-addicted individuals in the United States. With the need to increase the number of treatment opportunities available for opioid-dependent patients, Congress passed the Drug Addiction Treatment Act of 2000, which allows for the treatment of opioid dependence using buprenorphine by a properly licensed physician, including HIV primary care physicians. The integration of buprenorphine treatment for opioid addiction into HIV primary care thus provides a new treatment paradigm to address substance abuse in patients with HIV and HCV infections. (c) 2005 Lippincott Williams & Wilkins. C1 Natl Inst Drug Abuse, Ctr AIDS & Other Med Consequence Drug Abuse, NIH, Bethesda, MD 20892 USA. US Hlth Resources & Serv Adm, HIV AIDS Bur, Dept Hlth & Human Serv, Bethesda, MD USA. Yale Univ, Sch Med, Yale AIDS Program, New Haven, CT USA. RP Kresina, TF (reprint author), Natl Inst Drug Abuse, Ctr AIDS & Other Med Consequence Drug Abuse, NIH, 6001 Execut Blvd, Bethesda, MD 20892 USA. EM tk13v@nih.gov NR 34 TC 5 Z9 6 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0269-9370 J9 AIDS JI Aids PD OCT PY 2005 VL 19 SU 3 BP S221 EP S226 DI 10.1097/01.aids.0000192093.46506.e5 PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 988DF UT WOS:000233570900032 PM 16251822 ER PT J AU Willenbring, ML AF Willenbring, ML TI Integrating care for patients with infectious, psychiatric, and substance use disorders: concepts and approaches SO AIDS LA English DT Article; Proceedings Paper CT Symposium on HIV/Hepatitis C Co-Infection - Impact on Nervous System Disease Burden CY OCT 02-03, 2003 CL Bethesda, MD SP NIH DE AIDS; alcoholism; case management; disease management; drug abuse; hepatitis C; HIV; integrated care; psychiatric disorders; substance use disorders ID HEPATITIS-C VIRUS; INJECTION-DRUG USERS; DIRECTLY OBSERVED THERAPY; ACTIVE ANTIRETROVIRAL THERAPY; HUMAN-IMMUNODEFICIENCY-VIRUS; QUALITY-OF-LIFE; RANDOMIZED CONTROLLED-TRIAL; COOCCURRING MENTAL-HEALTH; PRIMARY MEDICAL-CARE; NEW-YORK-CITY AB Patients with chronic viral infections such as HIV/AIDS or hepatitis C often have multiple co-existing problems such as psychiatric and addictive disorders, as well as social problems such as lack of housing, transportation and income that present challenging obstacles to successful management. Because services for these different problems are usually provided by different disciplines in varying locations, fragmentation of care can lead to treatment dropouts, lack of adherence, and poor outcomes. Integration strategies, ranging from simple efforts to improve communication and coordinate care to fully integrated multidisciplinary teams have been used to improve disease management. Although evidence for effectiveness is comprised primarily of observational studies of demonstration programmes, integration may be desirable on a pragmatic basis alone. Quality improvement strategies are attractive vehicles for implementing care integration and measuring its impact. Careful assessment of the problem to be solved and the development of targeted strategies will maximize chances of a successful outcome. (c) 2005 Lippincott Williams & Wilkins. C1 NIAAA, NIH, Bethesda, MD 20892 USA. RP Willenbring, ML (reprint author), NIAAA, NIH, 5635 Fishers Lane,Room 2047 MSC 9304, Bethesda, MD 20892 USA. EM mlw@niaaa.nih.gov NR 140 TC 41 Z9 41 U1 5 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0269-9370 J9 AIDS JI Aids PD OCT PY 2005 VL 19 SU 3 BP S227 EP S237 DI 10.1097/01.aids.0000192094.84624.c2 PG 11 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 988DF UT WOS:000233570900033 PM 16251823 ER PT J AU Choi, KH Wong, F Sy, FS AF Choi, KH Wong, F Sy, FS TI HIV/AIDS among Asians and Pacific Islanders in the United States SO AIDS EDUCATION AND PREVENTION LA English DT Editorial Material ID SAN-FRANCISCO; INTERCOURSE; RISK; HIV; MEN C1 Univ Calif San Francisco, Ctr AIDS Prevent Studies, San Francisco, CA 94105 USA. Georgetown Univ, Sch Nursing & Hlth Studies, Washington, DC 20057 USA. NIH, Bethesda, MD 20892 USA. RP Choi, KH (reprint author), Univ Calif San Francisco, Ctr AIDS Prevent Studies, 50 Beale St,Suite 1300, San Francisco, CA 94105 USA. EM khchoi@psg.ucsf.edu NR 8 TC 2 Z9 2 U1 0 U2 0 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0899-9546 J9 AIDS EDUC PREV JI Aids Educ. Prev. PD OCT PY 2005 VL 17 IS 5 BP III EP V DI 10.1521/aeap.2005.17.5.iii PG 3 WC Education & Educational Research; Public, Environmental & Occupational Health SC Education & Educational Research; Public, Environmental & Occupational Health GA 977WS UT WOS:000232834800001 PM 16255636 ER PT J AU Zaidi, IF Crepaz, N Song, RG Wan, CK Lin, LS Hu, DJ Sy, FS AF Zaidi, IF Crepaz, N Song, RG Wan, CK Lin, LS Hu, DJ Sy, FS TI Epidemiology of HIV/AIDS among Asians and Pacific Islanders in the United States SO AIDS EDUCATION AND PREVENTION LA English DT Article ID HIV RISK BEHAVIORS; SAN-FRANCISCO; AMERICAN MEN; SEX; PREVENTION; AIDS; PREVALENCE; HEALTH; COLOR AB Although the percentage of overall AIDS diagnoses remains low among Asian and Pacific Islanders (APIs) in the United States compared with other racial/ethnic groups, research on API risk behaviors and health status suggest that the low number of AIDS cases may not provide a full picture of the epidemic and issues faced by this understudied and underserved population. Data from national HIV/AIDS surveillance systems and the Behavioral Risk Factor Surveillance System (BRFSS) were examined to delineate the magnitude and course of the HIV/AIDS epidemic among APIs in the United States. Same-sex sexual activity is the main HIV risk for API men, whereas heterosexual contact is for API women. APIs are significantly less likely to report being tested for HIV despite the fact that a similar proportion of APIs and other racial/ethnic groups reported having HIV risk in the past 12 months. Given the enormous diversity among APIs in the United States it is important to collect detailed demographic information to improve race/ethnicity and HIV risk classification, conduct better behavioral and disease monitoring for informing prevention planning, and addressing cultural, linguistic, economic and legal barriers to HIV prevention among APIs. C1 Ctr Dis Control & Prevent, Global Aids Program, Surveillance & Infrastruct Dev Branch, Div HIV AIDS Prevent, Atlanta, GA 30333 USA. NIH, Natl Ctr Minor Hlth & Hlth Disparities, Bethesda, MD USA. RP Zaidi, IF (reprint author), Ctr Dis Control & Prevent, Global Aids Program, Surveillance & Infrastruct Dev Branch, Div HIV AIDS Prevent, 1600 Clifton Rd,Mailstop E-30, Atlanta, GA 30333 USA. EM IZaidi@cdc.gov NR 38 TC 27 Z9 27 U1 2 U2 4 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0899-9546 J9 AIDS EDUC PREV JI Aids Educ. Prev. PD OCT PY 2005 VL 17 IS 5 BP 405 EP 417 DI 10.1521/aeap.2005.17.5.405 PG 13 WC Education & Educational Research; Public, Environmental & Occupational Health SC Education & Educational Research; Public, Environmental & Occupational Health GA 977WS UT WOS:000232834800002 PM 16255637 ER PT J AU Sloand, E AF Sloand, E TI Hematologic complications of HIV infection SO AIDS REVIEWS LA English DT Review DE cytopenia; HIV; bone marrow failure; thrombosis; hematologic complications ID HUMAN-IMMUNODEFICIENCY-VIRUS; THROMBOTIC THROMBOCYTOPENIC PURPURA; NON-HODGKINS-LYMPHOMA; NECROSIS-FACTOR-ALPHA; MICROVASCULAR ENDOTHELIAL-CELLS; PNEUMOCYSTIS-CARINII PNEUMONIA; ACTIVE ANTIRETROVIRAL THERAPY; VIRAL ACTIVATION TRANSFUSION; HEMOLYTIC-UREMIC SYNDROME; PARVOVIRUS B19 INFECTION AB Treatment of HIV-infected patients with highly active antiretroviral therapy (HAART) has altered the natural history of human immunodeficiency virus (HIV) infection by decreasing the frequency of opportunistic infections and altering the expected frequency of hematologic complications and AIDS-related malignancies. Thrombotic thrombocytopenic purpura and thrombosis resulting from protein S deficiency are relatively rare complications of HIV in the United States in patients taking HAART, but are frequent in the developing world where these drugs are not available. Cytopenia, particularly anemia, are more common and result both from bone marrow failure and peripheral destruction. Hodgkin's and non-Hodgkin's lymphoma are still problematic in patients with advanced disease with high viral loads. This review will examine and discuss the diagnosis and management of the hematologic complications of HIV. C1 NHLBI, Hematol Branch, Div Intramural Res, Bethesda, MD 20892 USA. RP Sloand, E (reprint author), NHLBI, Hematol Branch, Div Intramural Res, Bldg 10,CRC 4E,Rm 5230, Bethesda, MD 20892 USA. EM sloande@nih.gov NR 105 TC 38 Z9 41 U1 0 U2 1 PU PERMANYER PUBLICATIONS PI BARCELONA PA MALLORCA, 310, BARCELONA, SPAIN SN 1139-6121 J9 AIDS REV JI Aids Rev. PD OCT-DEC PY 2005 VL 7 IS 4 BP 187 EP 196 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 999BN UT WOS:000234363800001 PM 16425959 ER PT J AU Mukamal, KJ Massaro, JM Ault, KA Mittleman, MA Sutherland, PA Lipinska, I Levy, D D'Agostino, RB Tofler, GH AF Mukamal, KJ Massaro, JM Ault, KA Mittleman, MA Sutherland, PA Lipinska, I Levy, D D'Agostino, RB Tofler, GH TI Alcohol consumption and platelet activation and aggregation among women and men: The Framingham Offspring Study SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE alcohol; platelets; thrombosis ID CORONARY-HEART-DISEASE; DENSITY-LIPOPROTEIN CHOLESTEROL; ACUTE MYOCARDIAL-INFARCTION; HEMOSTATIC FACTORS; P-SELECTIN; IN-VITRO; ETHANOL; RISK; WINE; BLOOD AB Background: Alcohol intake has been associated with lower platelet activity; however, few large-scale studies have included women, and to our knowledge, the relationship of alcohol intake with measures of platelet activation has not been studied. Methods: We performed a cross-sectional analysis of adults free of cardiovascular disease enrolled in the Framingham Offspring Study. Study physicians assessed alcohol consumption with a standardized questionnaire. We measured platelet activation in response to 1 and 5 Am of adenosine diphosphate (ADP) with a P-selectin assay among 1037 participants and platelet aggregability in response to ADP, epinephrine, and collagen among 2013 participants. Results: Alcohol consumption was inversely associated with P-selectin expression in response to I Am ADP (p = 0.007) and 5 mu m ADP (p = 0.02) among men but not women. Alcohol consumption was also inversely associated with platelet aggregation induced by ADP among both women (p = 0.04) and men (p trend = 0.008) and by epinephrine among men (p = 0.03) Conclusions: Alcohol consumption is inversely associated with both platelet activation and aggregation, particularly in men. Additional research is needed to determine whether these findings contribute to the contrasting associations of alcohol consumption with risk of thrombotic and hemorrhagic cardiovascular events. C1 Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. Maine Med Ctr, Res Inst, Scarborough, ME USA. NHLBI, Framingham Heart Dis Epidemiol Study, Framingham, MA USA. Royal N Shore Hosp, Div Cardiol, Sydney, NSW, Australia. RP Mukamal, KJ (reprint author), Beth Israel Deaconess Med Ctr, Dept Med, 330 Brookline Ave,Rose-114, Boston, MA 02215 USA. EM kmukamal@bidmc.harvard.edu OI Massaro, Joseph/0000-0002-2682-4812 FU NHLBI NIH HHS [R01-HL48157]; NIAAA NIH HHS [K23-AA00299] NR 45 TC 39 Z9 42 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD OCT PY 2005 VL 29 IS 10 BP 1906 EP 1912 DI 10.1097/01.alc.0000183011.86768.61 PG 7 WC Substance Abuse SC Substance Abuse GA 982JE UT WOS:000233153200018 PM 16269922 ER PT J AU Ble, A Windham, BG Bandinelli, S Taub, DD Volpato, S Bartali, B Tracy, RP Guralnik, JM Ferrucci, L AF Ble, A Windham, BG Bandinelli, S Taub, DD Volpato, S Bartali, B Tracy, RP Guralnik, JM Ferrucci, L TI Relation of plasma leptin to C-reactive protein in older adults (from the Invecchiare nel Chianti Study) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID RECEPTOR; OBESITY; STATE AB Obese subjects have higher circulating levels of C-reactive protein (CRP) than normal subjects, and it has been shown that CRP per se may contribute to atherogenesis. The mechanism linking increased fat mass with high CRP levels has not been exhaustively explained. It has been suggested that adipose tissue-produced cytokines, including interleukin-6, tumor necrosis factor-alpha, and interleukin-1 beta, represent the causal link between increased body fat and high CRP levels. It has been hypothesized that the hormone leptin, released by fat cells, may stimulate CRP production independent of cytokines. This study measured circulating leptin, CRP, interleukin-6, tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-8 in 946 community-dwelling older subjects (398 men, 548 women; age range 65 to 102 years) enrolled in a large population-based study. Confounders included demographics, functional, cognitive and affective status, diet and lifestyle, body composition, drugs, and chronic diseases. A direct association was found between leptin and CRP (p = 0.004), independent of cytokines and other possible confounders. The association was stronger in younger than in older subjects but was not influenced by gender or body mass index. In conclusion, these findings suggest that leptin may directly stimulate the production of CRP independent of fat-cell produced cytokines in older adults. (c) 2005 Elsevier Inc. All rights reserved. C1 NIA, Longitudinal Studies Sect, Clin Res Branch, NIH, Bethesda, MD 20892 USA. NIA, Immunol Lab, NIH, Bethesda, MD 20892 USA. NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA. Italian Natl Inst Res & Care Aging, Lab Clin Epidemiol, Florence, Italy. Univ Ferrara, Dept Clin & Expt Med, Sect Internal Med & Geriatr, I-44100 Ferrara, Italy. Cornell Univ, Div Nutr Sci, Ithaca, NY 14853 USA. Univ Vermont, Dept Pathol, Colchester, VT USA. RP Ferrucci, L (reprint author), NIA, Longitudinal Studies Sect, Clin Res Branch, NIH, Bethesda, MD 20892 USA. EM ferruccilu@grc.nia.nih.gov RI VOLPATO, STEFANO/H-2977-2014 OI VOLPATO, STEFANO/0000-0003-4335-6034 FU NIMHD NIH HHS [263 MD 821336, 263 MD 9164 13] NR 14 TC 32 Z9 34 U1 0 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD OCT 1 PY 2005 VL 96 IS 7 BP 991 EP 995 DI 10.1016/j.amjcard.2005.05.058 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 974YD UT WOS:000232626400022 PM 16188530 ER PT J AU Molloy, AM Mills, JL Cox, C Daly, SF Conley, M Brody, LC Kirke, PN Scott, JM Ueland, PM AF Molloy, AM Mills, JL Cox, C Daly, SF Conley, M Brody, LC Kirke, PN Scott, JM Ueland, PM TI Choline and homocysteine interrelations in umbilical cord and maternal plasma at delivery SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE choline; betaine; dimethylglycine; homocysteine; umbilical cord; neonate; pregnancy; folate; vitamin B-12 ID RAT-LIVER; PHOSPHOLIPID METHYLATION; METHOTREXATE TREATMENT; MICROBIOLOGICAL ASSAY; PARENTERAL-NUTRITION; FOLATE-DEFICIENCY; DNA METHYLATION; GLYCINE BETAINE; HUMANS; SERUM AB Background: Little is known about the interactions between choline and folate and homocysteine metabolism during pregnancy despite the facts that pregnancy places considerable stress on maternal folate and choline stores and that choline is a critical nutrient for the fetus. Choline, via betaine, is an important folate-independent source of methyl groups for remethylating homocysteine in liver. Objectives: Our aims were to examine the intermediates of choline oxidation in maternal and umbilical cord plasma and to determine the relations between this pathway and folate-dependent homocysteine remethylation. Design: Blood samples were taken from 201 pregnant women and, at delivery, from the umbilical cord veins of their healthy, full-term infants. The blood samples were analyzed for plasma free choline, betaine, dimethylglycine, folate, vitamin B-12, total homocysteme (tHcy), and creatinine concentrations. Results: Choline concentrations in umbilical cord plasma were approximate to 3 times those in maternal plasma (geometric x: 36.6 and 12.3 mu mol/L, respectively; P < 0.0001). Betaine and dimethylglycine concentrations were also significantly higher in umbilical cord than in maternal plasma. Choline was positively associated with tHcy (r = 0.34, P < 0.0001), betaine (r = 0.58, P < 0.0001), and dimethylglycine (r = 0.30, P < 0.0001) in maternal blood. Much weaker relations were seen in the fetal circulation. In a multiple regression model, choline was a positive predictor of maternal tHcy, whereas vitamin B-12 and betaine were negative predictors. Conclusions: The positive association between maternal choline and tHcy during pregnancy suggests that the high fetal demand for choline stimulates de novo synthesis of choline in maternal liver, with a resultant increase in tHcy concentrations. If this is confirmed, it may be appropriate to provide choline supplements during pregnancy to prevent elevated tHcy concentrations. C1 Univ Dublin Trinity Coll, Dept Biochem, Dublin 2, Ireland. Univ Dublin Trinity Coll, Dept Clin Med, Dublin 2, Ireland. Hlth Res Board, Dublin, Ireland. Coombe Womens Hosp, Dublin, Ireland. NICHD, Epidemiol Branch, US Dept HHS, NIH, Bethesda, MD USA. NHGRI, NIH, Bethesda, MD 20892 USA. Univ Bergen, LOCUS Homocysteine & Related Vitamins, Pharmacol Sect, Inst Med, N-5020 Bergen, Norway. RP Molloy, AM (reprint author), Univ Dublin Trinity Coll, Dept Biochem, Dublin 2, Ireland. EM amolloy@tcd.ie RI Ueland, Per/C-7340-2013 NR 53 TC 48 Z9 48 U1 2 U2 3 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 2005 VL 82 IS 4 BP 836 EP 842 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 973CN UT WOS:000232500600018 PM 16210714 ER PT J AU Newman, AB Lee, JS Visser, M Goodpaster, BH Kritchevsky, SB Tylavsky, FA Nevitt, M Harris, TB AF Newman, AB Lee, JS Visser, M Goodpaster, BH Kritchevsky, SB Tylavsky, FA Nevitt, M Harris, TB TI Weight change and the conservation of lean mass in old age: the Health, Aging and Body Composition Study SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE body composition; sarcopenia; weight loss; older adults ID X-RAY ABSORPTIOMETRY; FAT-FREE MASS; ELDERLY-MEN; MUSCLE MASS; BONE LOSS; LONGITUDINAL CHANGES; PHYSICAL-ACTIVITY; SKELETAL-MUSCLE; RISK-FACTORS; NHANES-I AB Background: Weight loss may contribute to the loss of lean mass with age. Objective: The objective was to evaluate the relation between weight loss or weight gain and changes in lean mass and fat mass in older adults. Design: We observed changes in weight and body composition during a 4-y period in 2163 men (47%) and women (53%) aged 70-79 y in the Health, Aging and Body Composition Study cohort. Whole-body and appendicular bone-free lean mass and fat mass were measured by using dual-energy X-ray absorptiometry. Results: Weight loss and weight gain were common. In both weight losers and weight gainers, changes in lean mass as a percentage of initial lean mass were substantially smaller than changes in fat mass as a percentage of initial fat mass. However, the difference between the change in lean mass and that in fat mass was more pronounced with weight gain than with weight loss, especially in men. Small amounts of lean loss and fat gain were noted with weight stability. In multivariate models, weight loss was strongly associated with lean mass loss in both men and women, especially in men whose weight loss was concurrent with a hospitalization. Conclusions: With weight change, a greater proportion of lean mass than of fat mass was conserved, but, especially in older men, significantly more lean mass was lost with weight loss than was gained with weight gain. These findings suggest that weight loss, even with regain, could accelerate sarcopenia in older adults. C1 Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15213 USA. VU Univ, Med Ctr, Inst Res Extramural Med, Amsterdam, Netherlands. Vrije Univ Amsterdam, Fac Earth & Life Sci, Dept Nutr & Hlth, Amsterdam, Netherlands. Wake Forest Univ, Sch Med, Dept Internal Med, Div Gerontol & Geriatr Med, Winston Salem, NC 27109 USA. Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA. Univ Calif San Francisco, Prevent Sci Grp, San Francisco, CA 94143 USA. NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. RP Newman, AB (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, 130 N Bellefield St,Room 532, Pittsburgh, PA 15213 USA. EM newmana@edc.pitt.edu RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 FU NIA NIH HHS [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106] NR 37 TC 159 Z9 163 U1 2 U2 12 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 2005 VL 82 IS 4 BP 872 EP 878 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 973CN UT WOS:000232500600023 PM 16210719 ER PT J AU Franks, PW Ravussin, E Hanson, RL Harper, IT Allison, DB Knowler, WC Tataranni, PA Salbe, AD AF Franks, PW Ravussin, E Hanson, RL Harper, IT Allison, DB Knowler, WC Tataranni, PA Salbe, AD TI Habitual physical activity in children: the role of genes and the environment SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE physical activity energy expenditure; physical activity level; genetics; children; twins; doubly labeled water ID DOUBLY LABELED WATER; BONE-MINERAL DENSITY; BODY-MASS INDEX; ENERGY-EXPENDITURE; INSULIN-RESISTANCE; RECEPTOR GENE; YOUNG ADULTHOOD; BLOOD-PRESSURE; OBESE SUBJECTS; UNITED-STATES AB Background: Understanding the factors that contribute to physical inactivity in children is important because sedentary behavior strongly relates to metabolic disorders such as obesity and diabetes. Objective: We aimed to quantify the genetic and environmental influences on physical activity energy expenditure (PAEE) in 100 sex-concordant dizygotic (n = 38) and monozygotic (n = 62) twin pairs aged 4-10 y. Design: Resting metabolic rate (RMR) was assessed by using respiratory gas exchange, total energy expenditure (TEE) by using doubly labeled water, and body composition by using dual-energy X-ray absorptiometry. Structural equation modeling was used to partition the phenotypic variance into additive genetic (a(2)) and common (c(2)) and unshared (e(2)) environmental components. Results: Because PAEE [TEE - (RMR + 0.1 x TEE)] depends on body weight, which is highly heritable, we tested several models: 1) after adjustment for age, sex, ethnicity, study date, season, and weight, a(2) explained none of the phenotypic variance in PAEE (95% CI: 0%, 38%), whereas c(2) and e(2) accounted for 69% (33 %, 77%; P = 0.001) and 31% (23%, 39%; P < 0.001) of the variance, respectively; 2) after adjustment for the cofactors in model 1, a(2) explained 19% of the phenotypic variance in TEE (0%, 60%; P = 0.13), whereas c(2) and e(2) accounted for 59% (16%, 79%; P = 0.007) and 23% (17%, 31%; P < 0.0001) of the variance, respectively; 3) in models adjusted as above (excluding weight), a(2) explained no variance in physical activity level (TEE/RMR) (0%, 32%; P = 0.50), whereas c(2) and e(2) explained 65% (34%, 60%; P = 0.001) and 35% (28%, 45%; P < 0.0001) of the variance, respectively. Conclusions: Our data suggest that the familial resemblance in physical activity in these children is explained predominantly by shared environmental factors and not by genetic variability. C1 NIDDKD, Diabet Epidemiol & Clin Res Stn, NIH, Phoenix, AZ 85014 USA. Pennington Biomed Res Ctr, Baton Rouge, LA USA. Univ Alabama, Sect Stat Genet, Dept Biostat, Birmingham, AL USA. Univ Alabama, Clin Nutr Res Ctr, Birmingham, AL USA. RP Franks, PW (reprint author), NIDDKD, Diabet Epidemiol & Clin Res Stn, NIH, 1550 E Indian Sch Rd, Phoenix, AZ 85014 USA. EM pfranks@niddk.nih.gov RI Hanson, Robert/O-3238-2015; OI Hanson, Robert/0000-0002-4252-7068; Allison, David/0000-0003-3566-9399 FU Intramural NIH HHS NR 56 TC 64 Z9 67 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 2005 VL 82 IS 4 BP 901 EP 908 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 973CN UT WOS:000232500600027 PM 16210723 ER PT J AU Mitchell, LE Weinberg, CR AF Mitchell, LE Weinberg, CR TI Evaluation of offspring and maternal genetic effects on disease risk using a family-based approach: The "pent'' design SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE alleles; epidemiologic methods; genotype; linkage disequilibrium; linkage (genetics); models; genetic; models; statistical ID NEURAL-TUBE DEFECTS; CASE-PARENT TRIADS; 5,10-METHYLENETETRAHYDROFOLATE REDUCTASE; ENVIRONMENT INTERACTIONS; ASSOCIATION; FETAL; SUSCEPTIBILITY; VARIANTS; GENOTYPE; LOCI AB Diseases that develop during gestation may be influenced by the genotype of the mother and the inherited genotype of the embryo/fetus. However, given the correlation between maternal and offspring genotypes, differentiating between inherited and maternal genetic effects is not straightforward. The two-step transmission disequilibrium test was the first, family-based test proposed for the purpose of differentiating between maternal and offspring genetic effects. However, this approach, which requires data from "pents" comprising an affected child, mother, father, and maternal grandparents, provides biased tests for maternal genetic effects when the offspring genotype is associated with disease. An alternative approach based on transmissions from grandparents provides unbiased tests for maternal and offspring genetic effects but requires genotype information for paternal grandparents in addition to pents. The authors have developed two additional, pent-based approaches for the evaluation of maternal and offspring genetic effects. One approach requires the assumption of genetic mating type symmetry (pent-1), whereas the other does not (pent-2). Simulation studies demonstrate that both of these approaches provide valid estimation and testing for offspring and maternal genotypic effects. In addition, the power of the pent-1 approach is comparable with that of the approach based on data using all four grandparents. C1 Texas A&M Univ, Syst Hlth Sci Ctr, Inst Biosci & Technol, Ctr Environm & Genet Med, Houston, TX 77030 USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. RP Mitchell, LE (reprint author), Texas A&M Univ, Syst Hlth Sci Ctr, Inst Biosci & Technol, Ctr Environm & Genet Med, 2121 W Holcombe Blvd, Houston, TX 77030 USA. EM lmitchell@ibt.tamhsc.edu FU Intramural NIH HHS; NICHD NIH HHS [HD39195, HD39081] NR 27 TC 22 Z9 22 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 2005 VL 162 IS 7 BP 676 EP 685 DI 10.1093/aje/kwi249 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 967PE UT WOS:000232102900010 PM 16093287 ER PT J AU Berg, K Bonham, V Boyer, J Brody, L Brooks, L Collins, F Guttmacher, A McEwen, J Muenke, M Olson, S Wang, VO Rodriguez, LL Vydelingum, N Warshauer-Baker, E AF Berg, K Bonham, V Boyer, J Brody, L Brooks, L Collins, F Guttmacher, A McEwen, J Muenke, M Olson, S Wang, VO Rodriguez, LL Vydelingum, N Warshauer-Baker, E CA Race Ethnicity Genetics Working TI The use of racial, ethnic, and ancestral categories in human genetics research SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Review ID MODERN HUMAN ORIGINS; LOW NUCLEOTIDE DIVERSITY; PUBLIC-HEALTH RESEARCH; POPULATION STRATIFICATION; HUMAN-EVOLUTION; COMMON DISEASE; DNA-SEQUENCES; HUMAN GENOME; SKIN COLOR; ALLELIC ASSOCIATION AB The global dispersal of anatomically modern humans over the past 100,000 years has produced patterns of phenotypic variation that have exerted-and continue to exert-powerful influences on the lives of individuals and the experiences of groups. The recency of our common ancestry and continued gene flow among populations have resulted in less genetic differentiation among geographically distributed human populations than is observed in many other mammalian species. Nevertheless, differences in appearance have contributed to the development of ideas about "race" and "ethnicity" that often include the belief that significant inherited differences distinguish humans. The use of racial, ethnic, and ancestral categories in genetics research can imply that group differences arise directly through differing allele frequencies, with little influence from socially mediated mechanisms. At the same time, careful investigations of the biological, environmental, social, and psychological attributes associated with these categories will be an essential component of cross-disciplinary research into the origins, prevention, and treatment of common diseases, including those diseases that differ in prevalence among groups. C1 NHGRI, Bethesda, MD 20892 USA. RP Olson, S (reprint author), 7609 Sebago Rd, Bethesda, MD 20817 USA. EM solon@nas.edu NR 205 TC 50 Z9 52 U1 6 U2 15 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 EI 1537-6605 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2005 VL 77 IS 4 BP 519 EP 532 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA 967QS UT WOS:000232106900001 ER PT J AU Carlton, VEH Hu, XL Chokkalingam, AP Schrodi, SJ Brandon, R Alexander, HC Chang, M Catanese, JJ Leong, DU Ardlie, KG Kastner, DL Seldin, MF Criswell, LA Gregersen, PK Beasley, E Thomson, G Amos, CI Begovich, AB AF Carlton, VEH Hu, XL Chokkalingam, AP Schrodi, SJ Brandon, R Alexander, HC Chang, M Catanese, JJ Leong, DU Ardlie, KG Kastner, DL Seldin, MF Criswell, LA Gregersen, PK Beasley, E Thomson, G Amos, CI Begovich, AB TI PTPN22 genetic variation: Evidence for multiple variants associated with rheumatoid arthritis SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID PROTEIN-TYROSINE-PHOSPHATASE; SINGLE-NUCLEOTIDE POLYMORPHISM; SYSTEMIC-LUPUS-ERYTHEMATOSUS; DISEASE-PREDISPOSING VARIANTS; JUVENILE IDIOPATHIC ARTHRITIS; AUTOIMMUNE-DISEASES; R620W POLYMORPHISM; REGULATORY POLYMORPHISM; PSORIATIC-ARTHRITIS; FUNCTIONAL VARIANT AB The minor allele of the R620W missense single-nucleotide polymorphism (SNP) (rs2476601) in the hematopoietic-specific protein tyrosine phosphatase gene, PTPN22, has been associated with multiple autoimmune diseases, including rheumatoid arthritis (RA). These genetic data, combined with biochemical evidence that this SNP affects PTPN22 function, suggest that this phosphatase is a key regulator of autoimmunity. To determine whether other genetic variants in PTPN22 contribute to the development of RA, we sequenced the coding regions of this gene in 48 white North American patients with RA and identified 15 previously unreported SNPs, including 2 coding SNPs in the catalytic domain. We then genotyped 37 SNPs in or near PTPN22 in 475 patients with RA and 475 individually matched controls (sample set 1) and selected a subset of markers for replication in an additional 661 patients with RA and 1,322 individually matched controls (sample set 2). Analyses of these results predict 10 common (frequency >1%) PTPN22 haplotypes in white North Americans. The sole haplotype found to carry the previously identified W620 risk allele was strongly associated with disease in both sample sets, whereas another haplotype, identical at all other SNPs but carrying the R620 allele, showed no association. R620W, however, does not fully explain the association between PTPN22 and RA, since significant differences between cases and controls persisted in both sample sets after the haplotype data were stratified by R620W. Additional analyses identified two SNPs on a single common haplotype that are associated with RA independent of R620W, suggesting that R620W and at least one additional variant in the PTPN22 gene region influence RA susceptibility. C1 Celera Diagnost, Alameda, CA 94502 USA. Celera Gen, Rockville, MD USA. Gen Collaborat Div SeraCare Life Sci, Cambridge, MA USA. NIAMSD, Genet & Gen Branch, NIH, Bethesda, MD 20892 USA. Univ Calif Davis, Dept Med, Rowe Program Human Genet, Davis, CA 95616 USA. Univ Calif San Francisco, Dept Med, Rosalind Russell Med Res Ctr Arthritis, San Francisco, CA 94143 USA. N Shore Long Isl Jewish Inst Med Res, Robert S Boas Ctr Gen & Human Genet, Manhasset, NY USA. Univ Calif Berkeley, Dept Integrat Biol, Berkeley, CA 94720 USA. Univ Texas, MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. RP Begovich, AB (reprint author), Celera Diagnost, 1401 Harbor Bay Pkway, Alameda, CA 94502 USA. EM ann.begovich@celeradiagnostics.com OI Schrodi, Steven/0000-0003-2304-8528 FU NCRR NIH HHS [5 M01 RR-00079, M01 RR000079]; NHGRI NIH HHS [HG02275, R01 HG002275]; NIAMS NIH HHS [N01-AR-7-2232, R01-AR44222]; NIGMS NIH HHS [GM35326, R01 GM035326] NR 68 TC 148 Z9 157 U1 3 U2 7 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2005 VL 77 IS 4 BP 567 EP 581 DI 10.1086/468189 PG 15 WC Genetics & Heredity SC Genetics & Heredity GA 967QS UT WOS:000232106900005 PM 16175503 ER PT J AU Weinberg, CR Umbach, DM AF Weinberg, CR Umbach, DM TI A hybrid design for studying genetic influences on risk of diseases with onset early in life SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID CASE-PARENT TRIADS; LINKAGE DISEQUILIBRIUM; POPULATION STRATIFICATION; RELATIVE RISKS; ASSOCIATION; GENOTYPE; TESTS AB Studies of genetic contributions to risk can be family-based, such as the case-parents design, or population-based, such as the case-control design. Both provide powerful inference regarding associations between genetic variants and risks, but both have limitations. The case-control design requires identifying and recruiting appropriate controls, but it has the advantage that nongenctic risk factors like exposures can be assessed. For a condition with an onset early in life, such as a birth defect, one should also genotype the mothers of cases and the mothers of controls to avoid potential confounding due to maternally mediated genetic effects acting on the fetus during gestation. The case-parents approach is less vulnerable than the case-mother/control-mother approach to biases due to population structure and self-selection. The case-parents approach also allows access to epigenetic phenomena like imprinting, but it cannot evaluate the role of nongenetic cofactors like exposures. We propose a hybrid design based on augmenting a set of affected individuals and their parents with a set of unaffected, unrelated individuals and their parents. The affected individuals and their parents are all genotyped, whereas only the parents of unaffected individuals are genotyped, although exposures are ascertained for both affected and unaffected offspring. The proposed hybrid design, through log-linear, likelihood-based analysis, allows estimation of the relative risk parameters, can provide more power than either the case-parents approach or the case-mother/control-mother approach, permits straightforward likelihood-ratio tests for bias due to mating asymmetry or population stratification, and admits valid alternative analyses when mating is asymmetric or when population stratification is detected. C1 Natl Inst Environm Hlth Sci, Biostat Branch, Res Triangle Pk, NC 27709 USA. RP Weinberg, CR (reprint author), Natl Inst Environm Hlth Sci, Biostat Branch, Res Triangle Pk, NC 27709 USA. EM weinber2@niehs.nih.gov FU Intramural NIH HHS NR 19 TC 42 Z9 44 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2005 VL 77 IS 4 BP 627 EP 636 DI 10.1086/496900 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 967QS UT WOS:000232106900010 PM 16175508 ER PT J AU Chen, ZH Zheng, G Ghosh, K Li, ZH AF Chen, ZH Zheng, G Ghosh, K Li, ZH TI Linkage disequilibrium mapping of quantitative-trait loci by selective genotyping SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID POPULATION; PAIRS AB The principles of linkage disequilibrium mapping of dichotomous diseases can be well applied to the mapping of quantitative-trait loci through the method of selective genotyping. In 1999, M. Slatkin considered a truncation selection (TS) approach. We propose in this report an extended TS approach and an extreme-rank-selection (ERS) approach. The properties of these selection approaches are studied analytically. By using a simulation study, we demonstrate that both the extended TS approach and the ERS approach provide remarkable improvements over Slatkin's original TS approach. C1 Natl Univ Singapore, Dept Stat & Appl Probabil, Singapore 117543, Singapore. NHLBI, Div Epidemiol & Clin Applicat, Off Biostat Res, Bethesda, MD 20892 USA. George Washington Univ, Dept Stat, Washington, DC USA. NCI, Biostat Branch, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv,NIH, Washington, DC USA. RP Chen, ZH (reprint author), Natl Univ Singapore, Dept Stat & Appl Probabil, 3 Sci Dr 2, Singapore 117543, Singapore. EM stachenz@nus.edu.sg FU NEI NIH HHS [R01 EY014478, EY014478] NR 13 TC 32 Z9 34 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT PY 2005 VL 77 IS 4 BP 661 EP 669 DI 10.1086/491658 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 967QS UT WOS:000232106900014 PM 16175512 ER PT J AU Kamari, Y Sharabi, Y Leiba, A Peleg, E Apter, S Grossman, E AF Kamari, Y Sharabi, Y Leiba, A Peleg, E Apter, S Grossman, E TI Peripartum hypertension from pheochromocytoma: A rare and challenging entity SO AMERICAN JOURNAL OF HYPERTENSION LA English DT Article DE pheochromocytoma; pregnancy; hypertension ID CATECHOLAMINE-INDUCED CARDIOMYOPATHY; MALIGNANT PHEOCHROMOCYTOMA; DILATED CARDIOMYOPATHY; PREGNANCY; LOCALIZATION; MANAGEMENT; DIAGNOSIS; PATIENT; METYROSINE AB Background: Pheochromocytoma, a rare and usually curable cause of hypertension, is characterized by symptoms and signs related to increased catecholamine secretion. Pregnancy can elicit clinical manifestations of otherwise unrecognized pheochromocytorna. Methods and Results: Four women, ranging in age from 27 to 37 years, were referred to the hypertension clinic with the following presentations: 1) a 35-year-old woman, diagnosed with gestational hypertension and headaches during the third trimester of her pregnancy and 5 months after delivery, was hospitalized with pulmonary edema. Echocardiography revealed severe dilated left ventricular (LV) dysfunction. Cardiac function was normalized after surgical resection of a pheochromocytoma from her left adrenal; 2) a 37-year-old woman suffered from preeclampsia, persistent hypertension and orthostatic hypotension after a cesarean section. A diagnostic work-up revealed a catecholamine-secreting paraganglioma in the retroperitoneum. The patient underwent a laparosopic resection of the tumor; 3) a 27-year-old woman suffered from hypertension and episodes of palpitations, sweating, and dyspnea in the first trimester of her pregnancy. An ultrasound revealed a 5-cm mass in the left adrenal. She underwent a left adrenalectomy at the 17th week of pregnancy, which confirmed the diagnosis of pheochromocytoma; 4) a 34-year-old woman, at the 26th week of pregnancy, presented with an acute loss of vision and blood pressure of 230/140 mm Hg. Fundoscopy showed papilledema with soft exudates in both eyes. Chemical studies were positive and imaging revealed a left adrenal pheochromocytoma. Despite aggressive medical treatment, fetal distress mandated a laparotomy at the end of the 28th week of pregnancy. A healthy newborn was delivered and resection of the adrenal tumor confirmed the diagnosis of pheochromocytoma. Conclusions: Although rare, pheochromocytoma can cause severe peripartum hypertension. Screening for pheochromocytoma, ideally with plasma-free metanephrines, should be considered in cases of peripartum hypertension. C1 NINDS, Clin Neurocardiol Sect, NIH, Bethesda, MD 20892 USA. Tel Aviv Univ, Sackler Sch Med, Chaim Sheba Med Ctr, Dept Internal Med D, IL-52621 Tel Hashomer, Israel. Tel Aviv Univ, Sackler Sch Med, Chaim Sheba Med Ctr, Hypertens Unit, IL-52621 Tel Hashomer, Israel. RP Sharabi, Y (reprint author), NINDS, Clin Neurocardiol Sect, NIH, Bethesda, MD 20892 USA. EM sharabiy@ninds.nih.gov NR 36 TC 16 Z9 16 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0895-7061 J9 AM J HYPERTENS JI Am. J. Hypertens. PD OCT PY 2005 VL 18 IS 10 BP 1306 EP 1312 DI 10.1016/j.amjhyper.2005.04.021 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 973EK UT WOS:000232505500009 PM 16202853 ER PT J AU O'Leary, VB Milis, JL Parle-McDermott, A Pangilinan, F Molloy, AM Cox, C Weiler, A Conley, M Kirke, PN Scott, JM Brody, LC AF O'Leary, VB Milis, JL Parle-McDermott, A Pangilinan, F Molloy, AM Cox, C Weiler, A Conley, M Kirke, PN Scott, JM Brody, LC CA Members Birth Defects Res Grp TI Screening for new MTHFR polymorphisms and NTD risk SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE MTHFR; NTD; sequencing; SNP; 677C > T; P39P; R594Q ID NEURAL-TUBE DEFECTS; METHYLENETETRAHYDROFOLATE REDUCTASE MTHFR; 5,10-METHYLENETETRAHYDROFOLATE REDUCTASE; COMMON MUTATION; GENE; FOLATE; HAPLOTYPE; DISEASE; POPULATION; PATHWAY AB The enzyme, 5,10-methylenetetrahydrofolate reductase (MTHFR) plays a key role in cellular folate metabolism. The A222V (677C-> T) polymorphism is a confirmed neural tube defect (NTD) risk factor within Irish and other populations. To search for other unknown single nueleotide polymorphisms (SNPs) that might play a role in the etiology of NTDs, we examined the entire MTHFR coding region in healthy individuals (n = 100). SNPs were identified using sequencing and database analysis and allele frequencies were determined in our Irish population. We identified P39P (116C-> T; T allele frequency 0.13) and previously reported R594Q (1793G-> A; Q allele frequency 0.07). We screened a large ethnically homogeneous Irish NTD cohort (n > 1,300) for P39P and R594Q. A possible association between NTD cases and P39P (P = 0.034) was found but this was not confirmed by transmission disequilibrium testing. R594Q also showed some evidence of a NTD case association (P = 0.07). Further analysis indicated these observations are due to linkage disequilibrium. with A222V (677C-> T), and therefore these new SNPs are unlikely to be independent risk factors for NTDs. As rates of NTDs differ between ethnic groups, we examined allele and genotype frequencies of P39P and R594Q within African-American and American-Caucasian populations. This is the first NTD association study of both R594Q and the novel P39P. The association with NTD risk reported for these SNPs is driven by the linkage disequilibrium with the A222V (677C->T) NTD risk factor. Published 2005 Wiley-Liss, Ine(dagger). C1 Univ Dublin Trinity Coll, Dept Biochem, Dublin 2, Ireland. NICHHD, Dept Hlth & Human Serv, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD 20892 USA. NHGRI, Dept Hlth & Human Serv, Genome Technol Branch, Bethesda, MD 20892 USA. Univ Dublin Trinity Coll, Dept Clin Med, Dublin 2, Ireland. Hlth Res Board, Child Hlth Epidemiol Div, Dublin, Ireland. RP O'Leary, VB (reprint author), Univ Dublin Trinity Coll, Dept Biochem, Dublin 2, Ireland. EM olearyv@tcd.ie OI Molloy, Anne/0000-0002-1688-9049; O'Leary, Valerie/0000-0003-1171-9830 FU Intramural NIH HHS; NICHD NIH HHS [N0IHD23163] NR 29 TC 15 Z9 15 U1 0 U2 1 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 1 PY 2005 VL 138A IS 2 BP 99 EP 106 DI 10.1002/ajmg.a.30846 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 969MV UT WOS:000232239200004 PM 16145688 ER PT J AU Schellinger, PD Warach, S AF Schellinger, PD Warach, S TI Location, location, location: Angiography discerns early MR imaging vessel signs due to proximal arterial occlusion and distal collateral flow - Reply SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Letter C1 NINDS, NIH, Bethesda, MD 20892 USA. Univ Heidelberg, Dept Neurol, Heidelberg, Germany. RP Schellinger, PD (reprint author), NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD OCT PY 2005 VL 26 IS 9 BP 2433 EP 2434 PG 2 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 973UJ UT WOS:000232547800050 ER PT J AU Guido, RS Jeronimo, J Schiffman, M Solomon, D AF Guido, RS Jeronimo, J Schiffman, M Solomon, D CA ALTS Grp TI The distribution of neoplasia arising on the cervix: Results from the ALTS trial SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE cervical intraepithelial neoplasia; cervical cancer; lesion location ID ATYPICAL SQUAMOUS-CELLS; ASCUS-LSIL TRIAGE; HUMAN-PAPILLOMAVIRUS; UNDETERMINED SIGNIFICANCE; MANAGEMENT STRATEGIES; WOMEN; ABNORMALITIES; LESIONS; CANCER AB Objective: This study was undertaken to evaluate the topographic distribution of precancerous intraepithelial lesions on the cervix. Study design: We studied the distribution of cervical biopsies and location of acetowhite lesions as determined by cervigrams among women who underwent a colposcopic examination and biopsy during the ASCUS-LSIL Triage Study (ALTS). Results: More biopsies were taken in the 12 o'clock (41:4%) and 6 o'clock (28.4%) quadrants than in 3 o'clock and 9 o'clock quadrant (15.8% and 14.5%, respectively) (P<.001). The proportion of abnormal histology per biopsy, and the grade of neoplasia, did not vary significantly by position. Cervigrams demonstrated visible intraepithelial lesions and acetowhitening more common on the anterior and posterior quadrants of the cervix. Conclusion: More cervical intraepithelial neoplasia might develop at the anterior and posterior lips of the cervix. However, the evidence is weak and confounded by a tendency of the anterior and posterior quadrants to be acetowhite even in the absence of cervical intraepithelial neoplasia. (C) 2005 Mosby, Inc. All rights reserved. C1 Univ Pittsburgh, Magee Womens Hosp, Med Ctr Hlth Syst, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA 15213 USA. NCI, Div Canc Epidemiol & Genet, NIH, US Dept HHS, Rockville, MD USA. NCI, Breast & Gynecol Canc Res Grp, Div Canc Prevent,NIH, US Dept HHS, Rockville, MD USA. RP Guido, RS (reprint author), Univ Pittsburgh, Magee Womens Hosp, Med Ctr Hlth Syst, Dept Obstet Gynecol & Reprod Sci, 300 Halket St, Pittsburgh, PA 15213 USA. EM rguido@mail.magee.edu FU NCI NIH HHS [CN-55158, CN-55105, CN-55153, CN-55154, CN-55155, CN-55156, CN-55157, CN-55159] NR 17 TC 19 Z9 20 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD OCT PY 2005 VL 193 IS 4 BP 1331 EP 1337 DI 10.1016/j.ajog.2005.05.008 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 971TQ UT WOS:000232408000007 PM 16202722 ER PT J AU Quintero, RA Huhta, J Suh, E Chmait, R Romero, R Angel, J AF Quintero, RA Huhta, J Suh, E Chmait, R Romero, R Angel, J TI In utero cardiac fetal surgery: Laser atrial septotomy in the treatment of hypoplastic left heart syndrome with intact atrial septum SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE hypoplastic left heart syndrome; intact atrial septum ID HYPERTENSION; DISEASE AB Objective: The purpose of this study was to report a novel technique, laser atrial septotomy, for the in utero treatment of hypoplastic left heart syndrome with intact atrial septum. Study design: In utero atria] septotomy by Neodymium-YAG laser photofulguration in a fetus with hypoplastic left heart syndrome (HLHS) and intact atrial septum was performed at 30 4/7 weeks of gestation. Percutaneous fetal cardiocentesis was performed to guide a contact (Neodymium-YAG) laser fiber into the right atrium with the objective of creating an interatrial communication by photofulguration of the septal tissue. Results: New onset of blood flow from the left to the right atrium was confirmed by color Doppler imaging during the procedure. The neoatrial septal defect remained patent until delivery. A 3400-g neonate was born by spontaneous vaginal delivery at 37 weeks of gestation. A first stage Norwood procedure was performed on the first day of life and surgical correction of an obstructed right pulmonary vein at .3 months. Although pulmonary vascular resistance was normal at cardiac catheterization at 2 months of age, the infant died at 5 months of age from multiple organ failure. An autopsy was declined. Conclusion: In utero laser atrial septotomy is feasible. Further experience is necessary to determine the risks and benefits of this technique for the treatment of fetuses hypoplastic left heart syndrome with intact atrial septum. (C) 2005 Mosby, Inc. All rights reserved. C1 St Josephs Womens Hosp, Florida Inst Fetal Diag & Therapy, Tampa, FL USA. Univ S Florida, Dept Pediat, St Petersburg, FL 33701 USA. St Josephs Childrens Hosp, Tampa, FL USA. NICHHD, Perinatol Res Branch, NIH, US Dept HHS, Bethesda, MD 20892 USA. RP Quintero, RA (reprint author), Florida Inst Fetal Diag & Therapy, 13601 Bruce B Downs Blvd,Suite 250, Tampa, FL 33613 USA. EM yvrq@aol.com NR 14 TC 26 Z9 26 U1 0 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD OCT PY 2005 VL 193 IS 4 BP 1424 EP 1428 DI 10.1016/j.ajog.2005.02.126 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 971TQ UT WOS:000232408000021 PM 16202736 ER PT J AU Goepfert, AR Varner, M Ward, K Macpherson, C Klebanoff, M Goldenberg, RL Mercer, B Meis, P Iams, J Moawad, A Carey, JC Leveno, K Wapner, R Caritis, SN Miodovnik, M Sorokin, Y O'Sullivan, MJ Van Dorsten, JP Langer, O AF Goepfert, AR Varner, M Ward, K Macpherson, C Klebanoff, M Goldenberg, RL Mercer, B Meis, P Iams, J Moawad, A Carey, JC Leveno, K Wapner, R Caritis, SN Miodovnik, M Sorokin, Y O'Sullivan, MJ Van Dorsten, JP Langer, O CA NICHD Maternal-Fetal Med Units Ne TI Differences in inflammatory cytokine and Toll-like receptor genes and bacterial vaginosis in pregnancy SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 51st Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 24-27, 2004 CL Houston, TX SP Soc Gynecol Invest DE cytokine gene polymorphism; toll-like receptor gene polymorphism; bacterial vaginosis; pregnancy ID PRETERM PREDICTION; ONLINE DATABASES; HUMAN-DISEASE; RISK-FACTORS; WOMEN; BIRTH; POLYMORPHISM; INFECTION; DELIVERY; METRONIDAZOLE AB Objective: This study was undertaken to estimate the frequency of inflammatory cytokine and Toll-like receptor gene polymorphisms in women with and without bacterial vaginosis (BV) in pregnancy. Study design: A secondary analysis was performed of pregnant women at less than 30 weeks' gestation enrolled as part of 2 multicenter studies. Eight hundred eighty-five women were assessed for BV (defined as Nugent's vaginal Gram stain score 7-10 and a pH >4.5). Comparisons were made between women with or without BV. Extracted maternal DNA was analyzed for 7 cytokine (interleukin [IL] 1 beta-511, IL1 beta Exon 5 +3954, IL6-174, 118-845, IL10-1082, tumor necrosis factor alpha-238 [TNF alpha-238], TNF alpha-308) and 2 Toll-like receptor (TLR-4 299, TLR-4 399) gene polymorphisms. Results: BV was diagnosed in 497 women and 388 did not have BV. Genotype and allele frequency analyses revealed associations with BV and polymorphisms; at the IL1 beta Exon 5 + 3954, IL6-174, IL10-1082, and TLR-4 399 loci. Women with BV were less likely to be homozygous (C/C) for IL1 beta Exon 5 +3954 (P=.04). Women with BV were also less likely to have polymorphisms at the IL10-1082 (P=.03) and TLR-4, 399 (P =.04) loci in the univariate analysis. Women with BV were more likely to be heterozygous (G/C) for the IL6-174 genotype (P <.0001). Multivariate analysis, controlling for maternal race, confirmed the following associations with BV: IL1 beta Exon 5 +3954 (odds Ratio [OR] 0.5, 95% CI 0.3-0.9) and IL6-174 (OR 2.2, 95% CI 1.6-3.1). In addition, polymorphism at the IL8-845 locus was associated with a decreased risk for BV (OR 0.6, 95% CI 0.4-1.0). Conclusion: After controlling for race, polymorphisms at the IL1 beta Exon 5 + 3954, IL6-174, and IL8-845 loci were associated with an altered rate of BV in pregnancy. (C) 2005 Mosby, Inc. All rights reserved. C1 Univ Alabama Birmingham, Dept Obstet & Gynecol, Birmingham, AL 35294 USA. Univ Utah, Sch Med, Dept Obstet & Gynecol, Salt Lake City, UT 84132 USA. George Washington Univ, Ctr Biostat, Washington, DC USA. NICHHD, Rockville, MD USA. Univ Tennessee, Dept Obstet, Memphis, TN USA. Univ Tennessee, Dept Gynecol, Memphis, TN USA. Wake Forest Univ, Winston Salem, NC 27109 USA. Ohio State Univ, Columbus, OH 43210 USA. Univ Chicago, Chicago, IL 60637 USA. Univ Oklahoma, Oklahoma City, OK USA. SW Texas State Univ, Dallas, TX USA. Thomas Jefferson Univ, Philadelphia, PA 19107 USA. Univ Pittsburgh, Magee Womens Hosp, Pittsburgh, PA 15213 USA. Univ Cincinnati, Cincinnati, OH USA. Wayne State Univ, Detroit, MI USA. Univ Miami, Miami, FL 33152 USA. Med Univ S Carolina, Charleston, SC 29425 USA. Univ Texas San Antonio, San Antonio, TX 78285 USA. RP Goepfert, AR (reprint author), Univ Alabama Birmingham, Dept Obstet & Gynecol, Birmingham, AL 35294 USA. RI Varner, Michael/K-9890-2013 OI caritis, steve/0000-0002-2169-0712; Varner, Michael/0000-0001-9455-3973 FU NICHD NIH HHS [U10 HD27869, U01 HD19897, U01 HD36801, U10 HD21410, U10 HD21414, U10 HD27860, U10 HD27861, U10 HD27883, U10 HD27889, U10 HD27905, U10 HD27915, U10 HD27917, U10 HD34116, U10 HD34122, U10 HD34136, U10 HD34208, U10 HD34210] NR 26 TC 28 Z9 34 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD OCT PY 2005 VL 193 IS 4 BP 1478 EP 1485 DI 10.1016/j.ajog.2005.03.053 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 971TQ UT WOS:000232408000028 PM 16202743 ER PT J AU Hediger, ML Luke, B Gonzalez-Quintero, VH Martin, D Nugent, C Witter, FR Mauldin, JG Newman, RB AF Hediger, ML Luke, B Gonzalez-Quintero, VH Martin, D Nugent, C Witter, FR Mauldin, JG Newman, RB TI Fetal growth rates and the very preterm delivery of twins SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE twins; fetal growth; very preterm delivery ID BIRTH-WEIGHT; INTRAUTERINE GROWTH; GESTATIONAL-AGE; RISK; RETARDATION; DISCORDANCE; PREMATURE; STANDARDS; OUTCOMES; INFANTS AB Objective: Our objective was to determine whether slow fetal growth rates and twin growth patterns from 20 weeks' gestation to delivery are associated with very preterm delivery. Study design: Available charts were reviewed for twin pregnancies, delivered between 1979 and 2002, at 4 U.S. medical centers. The sample of 1612 pregnancies delivered at 28 week's gestation or greater and had at least 2 ultrasound evaluations of fetal size from 20 to 28 weeks or from 28 weeks to delivery for estimation of fetal growth rates (grams per week). Slow fetal growth (below the 10th percentile) was defined as less than 90 grams per week at 20-28 weeks and 168 g/week from 28 weeks to delivery. The main outcome measure was the timing of delivery. Results: Of the women delivering twins, 5.3% delivered extremely preterm (28-30 weeks), 8.5% very preterm (31-32 weeks), and 40.1% preterm (33-36 weeks). Patterns of growth for the pair were highly associated with very preterm delivery. Compared with neither growing slowly (1.7%), 4.9% delivered very preterm if only I twin grew slowly. Very preterm, was 14.6% (adjusted odds ratio 9.81; 95% confidence interval, 3.50-27.48) with both growing slowly from 28 weeks on and 20.0% (adjusted odds ratio 15.04; 95% confidence interval 5.13-44.11) with both growing slowly over both intervals. Survival analyses indicated that twins with normal growth in both intervals remained undelivered for a significantly longer number of days (P <.0001) than pairs in which one or both twins were growing slowly. Conclusion: Very preterm delivery of twins seems to be preceded by slowed or compromised fetal growth for the pair. (C) 2005 Mosby, Inc. All rights reserved. C1 NICHHD, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Univ Miami, Sch Nursing & Hlth Studies, Coral Gables, FL 33124 USA. Univ Miami, Sch Med, Dept Obstet & Gynecol, Miami, FL 33101 USA. Univ Michigan, Sch Med, Dept Gynecol & Obstet, Ann Arbor, MI 48109 USA. Johns Hopkins Univ, Sch Med, Dept Gynecol & Obstet, Baltimore, MD 21205 USA. Med Univ S Carolina, Dept Obstet & Gynecol, Charleston, SC 29425 USA. RP Hediger, ML (reprint author), NICHHD, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, NIH,Dept Hlth & Human Serv, Bldg 6100,Room 7B03,MSC 7510,9000 Rockville Pike, Bethesda, MD 20892 USA. EM hedigerm@exchange.nih.gov NR 41 TC 7 Z9 7 U1 0 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD OCT PY 2005 VL 193 IS 4 BP 1498 EP 1507 DI 10.1016/j.ajog.2005.03.040 PG 10 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 971TQ UT WOS:000232408000031 PM 16202746 ER PT J AU Toso, L Poggi, SH Abebe, D Roberson, R Dunlap, V Park, J Spong, CY AF Toso, L Poggi, SH Abebe, D Roberson, R Dunlap, V Park, J Spong, CY TI N-Methyl-D-aspartate subunit expression during mouse development altered by in utero alcohol exposure SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE fetal alcohol syndrome; alcohol N-methyl-D-aspartate receptors; mouse development; learning ID PRENATAL ETHANOL EXPOSURE; MECHANISM; GROWTH AB Objective: Alcohol-related neurodevelopmental disorders are contributors to long-term learning disabilities. By using a model for fetal alcohol syndrome, we have shown that prenatal alcohol exposure results in adult learning deficits of unknown mechanisms. In the developing hippocampus, the N-methyl-D-aspartate (NMDA) receptor subunit NR2B triggers long-term potentiation, fundamental to learning and memory; this is supplemented by the less plastic NR2A subunit in the adult. To understand the mechanism of learning deficits in FAS, we evaluated NR2B and NR2A expression in embryonic and adult mice. Study design: Pregnant C57BI6/J mice were treated on gestational day 8 with alcohol or control (saline solution). Embryos were harvested at 6 hours, 24 hours, and 10 days, and brains from adult offspring were collected at 3 months (after evaluation for learning deficit). Calibrator-normalized relative real-time polymerase chain reaction was performed for NR2B and NR2A with glyceraldehyde-3-phosphate dehydrogenase standardization. Statistical analysis included analysis of variance. Results: At 6 hours, NR2B expression in the alcohol-exposed embryos was higher than in controls (P <.01). NR2A was not expressed in either group. By 24 hours there was no difference-exposed animals (P =.02). in NR2B (P =.3). However, at 10 days NR2B was lower in alcohol In the adult brains there was a relative decrease in NR2B (P =.03) and an increase in NR2A (P <.01). Conclusion: Prenatal alcohol exposure during development induces NR2B expression deregulation in the embryos that persists until adulthood, when a relative increase in the less modifiable subunit NR2A occurs. This alteration in NMDA receptor subunits may underlie the learning abnormalities in fetal alcohol syndrome. (C) 2005 Mosby, Inc. All rights reserved. C1 NICHD, Unit Perinatal & Dev Neurobiol, NIH, Bethesda, MD 20892 USA. NIAAA, NIH, Bethesda, MD USA. Georgetown Univ Hosp, Dept Obstet & Gynecol, Washington, DC 20007 USA. RP Toso, L (reprint author), NICHD, Unit Perinatal & Dev Neurobiol, NIH, Bldg 9,R 1W125,9 Mem Dr, Bethesda, MD 20892 USA. EM laura_toso@hotmail.com NR 14 TC 21 Z9 25 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD OCT PY 2005 VL 193 IS 4 BP 1534 EP 1539 DI 10.1016/j.ajog.2005.02.105 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 971TQ UT WOS:000232408000037 PM 16202752 ER PT J AU Weil, RJ Palmieri, DC Bronder, JL Stark, AM Steeg, PS AF Weil, RJ Palmieri, DC Bronder, JL Stark, AM Steeg, PS TI Breast cancer metastasis to the central nervous system SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Review ID BLOOD-BRAIN-BARRIER; CARCINOMA CELL-LINES; NUDE-MICE; PROGNOSTIC-FACTORS; RANDOMIZED-TRIAL; RADIATION-THERAPY; ENDOTHELIAL-CELLS; NEU ONCOGENE; LUNG-CANCER; IN-VITRO AB Clinically symptomatic metastases to the central nervous system (CNS) occur in similar to 10 to 15% of patients with metastatic beast cancer. CNS metastases are traditionally viewed as a late complication of systemic disease, for which few effective treatment options exist. Recently, patients with Her-2-positive breast tumors who were treated with trastuzumab have been reported to develop CNS metastases at higher rates, often while responding favorably to treatment. The blood:brain barrier and the unique brain microenvironment are hypothesized to promote distinct molecular features in CNS metastases that may require tailored therapeutic approaches. New research approaches using cell lines that reliably and preferentially metastasize in vivo to the brain have been reported. Using such model systems, as well as in vitro analogs of blood-brain barrier penetration and tissue-based studies, new molecular leads into this disease are unfolding. C1 Cleveland Clin Fdn, Lerner Res Inst, Brain Tumor Inst, Cleveland, OH 44195 USA. NCI, Womens Canc Sect, Pathol Lab, NIH, Bethesda, MD 20892 USA. Univ Schleswig Holstein, Dept Neurosurg, Kiel, Germany. RP Weil, RJ (reprint author), Cleveland Clin Fdn, Lerner Res Inst, Brain Tumor Inst, 9500 Euclid Ave,ND4-40, Cleveland, OH 44195 USA. EM weilr@ccf.org RI Palmieri, Diane/B-4258-2015; OI Mason, Julie/0000-0002-5144-175X NR 69 TC 204 Z9 210 U1 2 U2 7 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 2005 VL 167 IS 4 BP 913 EP 920 DI 10.1016/S0002-9440(10)61180-7 PG 8 WC Pathology SC Pathology GA 969OA UT WOS:000232242400001 PM 16192626 ER PT J AU Daniel, JA Elsasser, TH Martinez, A Steele, B Whitlock, BK Sartin, JL AF Daniel, JA Elsasser, TH Martinez, A Steele, B Whitlock, BK Sartin, JL TI Interleukin-1 beta and tumor necrosis factor-alpha mediation of endotoxin action on growth hormone SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE luteinizing hormone; cytokines; sheep; CD14; lipopolysaccharide ID GONADOTROPIN-RELEASING-HORMONE; OVINE PITUITARY-CELLS; LUTEINIZING-HORMONE; NEUROENDOCRINE REGULATION; INDUCED SUPPRESSION; LH-SECRETION; SHEEP; PLASMA; SOMATOSTATIN; EXPRESSION AB In humans and sheep, endotoxin (LPS) administration results in increased growth hormone (GH) concentrations. To determine the role of cytokines in the effect of LPS on GH, sheep were challenged with IL-1 beta or TNF-alpha. GH data were compared with results with LH, where the major effects of LPS are known to act via the hypothalamus. Intracerebroventricular (icv) administration of IL-1 beta or TNF-alpha did not alter plasma concentrations of GH. Endotoxin was then administered intravenously (iv) in combination with icv injection of IL-1 receptor antagonist (IL-1RA), TNF antagonist (sTNF-R1), or saline. Administration of LPS increased GH ( P < 0.0001), although coadministration of IL-1ra or sTNF-R1 icv did not alter GH response to LPS. In contrast, plasma concentrations of LH were profoundly inhibited by icv administration of either cytokine ( P < 0.03), but the LH response to LPS was not altered by cytokine antagonists. Intravenous administration of either IL-1 beta or TNF-alpha increased plasma concentrations of GH ( P < 0.0001). Administration of IL-1RA and sTNF-R1 iv prevented LPS-induced increases in GH. Although LH was suppressed by high iv doses of IL-1 beta ( P = 0.0063), the antagonists did not alter the LH response to LPS. To determine whether LPS might directly activate GH release, confocal microscopy revealed colocalization of CD14, the LPS receptor, with GH and, to a lesser extent, LH and some prolactin (PRL)-containing cells, but not ACTH or TSH. These data are consistent with the effects of LPS on GH secretion originating through peripheral cytokine presentation to the pituitary, as well as a potential to act directly on selective populations of pituitary cells via CD14. C1 Auburn Univ, Coll Vet Med, Dept Anat Physiol & Pharmacol, Auburn, AL 36849 USA. S Dakota State Univ, Brookings, SD 57007 USA. Agr Res Serv, USDA, Growth Biol Lab, Beltsville, MD USA. NCI, Cell & Canc Biol Branch, NIH, Bethesda, MD 20892 USA. RP Sartin, JL (reprint author), Auburn Univ, Coll Vet Med, Dept Anat Physiol & Pharmacol, Auburn, AL 36849 USA. EM sartijl@vetmed.auburn.edu RI Martinez, Alfredo/A-3077-2013; Whitlock, Brian/H-4198-2016 OI Martinez, Alfredo/0000-0003-4882-4044; Whitlock, Brian/0000-0001-7247-0982 NR 37 TC 19 Z9 19 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD OCT PY 2005 VL 289 IS 4 BP E650 EP E657 DI 10.1152/ajpendo.00489.2004 PG 8 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 962MV UT WOS:000231737800017 PM 15899940 ER PT J AU Ojaimi, C Li, W Kinugawa, S Post, H Csiszar, A Pacher, P Kaley, G Hintze, TH AF Ojaimi, C Li, W Kinugawa, S Post, H Csiszar, A Pacher, P Kaley, G Hintze, TH TI Transcriptional basis for exercise limitation in male eNOS-knockout mice with age: heart failure and the fetal phenotype SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE maximal oxygen consumption; respiratory exchange ratio; work; microarray; endothelial nitric oxide synthase ID NITRIC-OXIDE SYNTHASE; RECEPTOR-GAMMA COACTIVATOR-1; OXYGEN-CONSUMPTION; SKELETAL-MUSCLE; MITOCHONDRIAL BIOGENESIS; CONSCIOUS DOG; CARDIAC-HYPERTROPHY; TREADMILL EXERCISE; GENE-EXPRESSION; ACTIVATION AB Endothelium-derived nitric oxide (NO) is pivotal in regulating mitochondrial O-2 consumption ((V)over dotO(2)) and glucose uptake in mice. The aim of this study was to investigate the mechanism of age- and genotype-related exercise limitation in male endothelial NO synthase (eNOS)-knockout (KO, n=16) and wild-type (WT, n=19) mice. Treadmill testing was performed at 12, 14, 16, 18, and 21 mo of age. (V)over dotO(2), CO2 production, respiratory exchange ratio, and maximal running distance were determined during treadmill running. There were good linear correlations for increase of speed with increase of (V)over dotO(2). The difference between KO and WT mice was not significant at 12 mo but was significant at 18 mo. Linear regression showed that KO mice consumed more O-2 at the same absolute and relative workloads, suggesting that (V)over dotO(2) was not inhibited by NO in KO mice. KO mice performed 30-50% less work than WT mice at each age (work=vertical distance x weight). In contrast to WT mice, the work performed by KO mice significantly decreased from 17 +/- 1.4 m.kg at 12 mo to 9.4 +/- 1.7 m.kg at 21 mo. Running distance was significantly decreased from 334 +/- 27 m at 12 mo to 178 +/- 38 m at 21 mo, and maximal (V)over dotO(2), CO2 production, and respiratory exchange ratio per work unit were significantly higher in KO than in WT mice. Gene arrays showed evidence of a fetal phenotype in KO mice at 21 mo. In conclusion, age- and genotype-related exercise limitations in maximal work performed and maximal running distance in male eNOS-KO mice indicated that fetal phenotype and age were related to onset of heart failure. C1 New York Med Coll, Dept Physiol, Valhalla, NY 10595 USA. NIAAA, NIH, Bethesda, MD USA. RP Hintze, TH (reprint author), New York Med Coll, Dept Physiol, Valhalla, NY 10595 USA. EM Thomas_Hintze@nymc.edu RI Pacher, Pal/B-6378-2008; Kinugawa, Shintaro/E-1268-2012 OI Pacher, Pal/0000-0001-7036-8108; FU Intramural NIH HHS [Z99 AA999999]; NHLBI NIH HHS [HL-50142, HL-61029, P0-HL-43023] NR 61 TC 26 Z9 26 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD OCT PY 2005 VL 289 IS 4 BP H1399 EP H1407 DI 10.1152/ajpheart.00170.2005 PG 9 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 964IW UT WOS:000231875300011 PM 15879487 ER PT J AU Younes, A Pepe, S Yoshishige, D Caffrey, JL Lakatta, EG AF Younes, A Pepe, S Yoshishige, D Caffrey, JL Lakatta, EG TI Ischemic preconditioning increases the bioavailability of cardiac enkephalins SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE opioid peptides; heart; opioid peptide processing ID CANINE SINOATRIAL NODE; PRIMARY HEREDITARY CARDIOMYOPATHY; PREPROENKEPHALIN MESSENGER-RNA; PEPTIDE GENE-EXPRESSION; RAT-HEART; OPIOID RECEPTORS; MET-ENKEPHALIN; VAGAL BRADYCARDIA; HYPERTENSIVE RATS; SYRIAN-HAMSTER AB Growing evidence suggests that cardiac enkephalins and their receptors are involved in ischemic preconditioning (IPC). Because there is no evidence for vesicular storage of small bioactive enkephalins in the heart, studies were designed to test the hypothesis that ischemia depletes cardiac enkephalins and that IPC preserves the same enkephalins by accelerating their processing from the larger proenkephalin precursor ( PEP) pool. The precursors and two bioactive representatives, Met-enkephalin ( ME) and Met-enkephalin- Arg-Phe ( MEAP), were separated by size-exclusion chromatography and quantified by radioimmunoassay. Isolated perfused rat hearts were prepared and exposed to global ischemia. After 30 min of global ischemia and 40 min of reflow, the PEP pool was reduced ( from 17.99 +/- 1.52 to 14.20 +/- 2.38 pmol/g wet wt), MEAP increased by 53%, and ME declined by 68%. The sum of the two smaller peptides was unchanged (9.78 +/- 0.83 vs. 9.33 +/- 2.81). Thus the total enkephalin peptide content was not altered (27.77 +/- 1.69 vs. 24.10 +/- 4.75). Peptide distribution after ischemia and reflow was also unaltered by pretreatment with peptidase inhibitors. However, when the hearts were preconditioned, the PEP pool remained significantly lower and both of the bioactive peptides, MEAP and ME, were elevated ( + 49% and + 86%, respectively). The decline in the PEP pool was prevented by peptidase inhibition and the rise in MEAP was exaggerated. In separate protocols, synthetic enkephalins ( ME, MEAP, and Leuenkephalin) were added to the coronary inflow before 30 min of global ischemia and throughout the subsequent reflow. The added enkephalins ( 10(-8) M) had no inotropic effect on baseline function but completely prevented the mechanical dysfunction observed in untreated controls during reflow. Thus IPC appears to increase available bioactive enkephalins ( MEAP + ME) within the heart by enhancing synthesis of precursors and their subsequent processing from the PEP pool. C1 NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. Univ Auvergne, Inst Univ Technol, Aubiere, France. Monash Univ, Alfred Hosp, Dept Surg, Melbourne, Vic 3181, Australia. Baker Heart Res Inst, Wynn Domain, Melbourne, Vic, Australia. Univ N Texas, Hlth Sci Ctr, Ft Worth, TX USA. RP Lakatta, EG (reprint author), NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM lakattae@grc.nia.nih.gov NR 38 TC 16 Z9 16 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD OCT PY 2005 VL 289 IS 4 BP H1652 EP H1661 DI 10.1152/ajpheart.01110.2004 PG 10 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 964IW UT WOS:000231875300040 PM 16162869 ER PT J AU Cai, Q Ferraris, JD Burg, MB AF Cai, Q Ferraris, JD Burg, MB TI High NaCl increases TonEBP/OREBP mRNA and protein by stabilizing its mRNA SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE mRNA stability; hypertonicity ID ENHANCER-BINDING PROTEIN; MAMMALIAN-CELLS; CODING REGION; HUR BINDING; UV-LIGHT; ELEMENT; IDENTIFICATION; INVOLVEMENT; OSMOLYTES; TONICITY AB Hypertonicity increases mRNA and protein abundance of the transcription factor tonicity-responsive enhancer/osmotic response element binding protein (TonEBP/OREBP), contributing to increased transcription of downstream osmoprotective genes. Previously, this was attributed to increased transcription of TonEBP/OREBP because no change was found in its mRNA stability. However, there is no direct evidence for increased transcription, and the 3'-untranslated region (UTR) of TonEBP/OREBP contains numerous adenylate/uridylate-rich elements, which can modulate RNA stability. Therefore, we have reinvestigated the effect of hypertonicity on TonEBP/OREBP mRNA stability. We find that, in mouse inner medullary collecting duct cells, raising osmolality from 300 to 500 mosmol/kgH(2)O by adding NaCl increases TonEBP/OREBP mRNA to a peak of 2.3-fold after 4 h, followed by a decline. TonEBP/OREBP protein increases to a sustained peak of 3.0-fold at 8 h. To determine the stability of TonEBP/OREBP mRNA, we measured the rate of its decrease after inhibiting transcription with actinomycin D, finding that it is stabilized for 6 h after addition of NaCl. This stabilization is sufficient to explain the increase in mRNA without any change in transcription. To investigate how hypertonicity stabilizes TonEBP/OREBP mRNA, we tested luciferase reporters containing parts of the TonEBP/OREBP mRNA UTR. Inclusion of both the 5'- and 3'-UTR increases reporter activity, consistent with mRNA stabilization. Surprisingly, however, it is the 5'-UTR that stabilizes; the 3'-UTR, by itself, decreases reporter activity. We concluded that 1) hypertonicity stabilizes TonEBP/OREBP mRNA, contributing to its increase, and 2) stabilization depends on the presence of the 5'-UTR. C1 NHLBI, Kidney & Electrolyte Metab Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Burg, MB (reprint author), Bldg 10,Rm 6N260,10 Ctr Dr, Bethesda, MD 20892 USA. EM burgm@nhlbi.nih.gov NR 27 TC 42 Z9 43 U1 0 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 2005 VL 289 IS 4 BP F803 EP F807 DI 10.1152/ajprenal.00448.2004 PG 5 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 963VD UT WOS:000231833300017 PM 15900024 ER PT J AU Lemley, KV Boothroyd, DB Blouch, KL Nelson, RG Jones, LI Olshen, RA Myers, BD AF Lemley, KV Boothroyd, DB Blouch, KL Nelson, RG Jones, LI Olshen, RA Myers, BD TI Modeling GFR trajectories in diabetic nephropathy SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article; Proceedings Paper CT 35th Annual Meeting of the American-Society-of-Nephrology CY OCT 30-NOV 06, 2002 CL PHILADELPHIA, PA SP Amer Soc Nephrol DE Pima Indian; smoothing splines; iothalamate clearance; permutation testing; progression ID CONVERTING ENZYME GENE; PIMA-INDIANS; RENAL-DISEASE; SPLINE FUNCTIONS; MELLITUS; POLYMORPHISM; PROGRESSION AB In an 8-year longitudinal study of Pima Indians with type 2 diabetes and nephropathy, we used statistical techniques that are novel and depend on minimal assumptions to compare longitudinal measurements of glomerular filtration rate (GFR). Individuals enrolled with new-onset microalbuminuria either progressed to macroalbuminuria (progressors, n = 13) or did not progress (nonprogressors, n = 13) during follow-up. Subjects with new-onset macroalbuminuria at screening were also followed (n = 22). Patients had their GFR determined serially by urinary iothalamate clearances (average 11 clearances; range 6 - 19). GFR courses of individuals were modeled using an adaptation of smoothing and regression cubic B-splines. Group comparisons were based on five-component vectors of fitted GFR values using a permutation approach to a Hotelling's T(2) statistic. GFR profiles of initially microalbuminuric progressors differed significantly from those of nonprogressors (P = 0.003). There were no significant baseline differences between progressors and nonprogressors with respect to any measured clinical parameters. The course of GFR in the first 4 yr following progression to macroalbuminuria in initially microalbuminuric subjects did not differ from that in newly screened macroalbuinuric subjects (P = 0.27). Without imposing simplifying models on the data, the statistical techniques used demonstrate that the courses of decline of GFR in definable subgroups of initially microalbuminuric diabetic Pima Indians, although generally progressive, follow distinct trajectories that are related to the extent of glomerular barrier dysfunction, as reflected by the evolution from microalbuminuria to macroalbuminuria. C1 Stanford Univ, Sch Med, Div Pediat Nephrol, Dept Med, Stanford, CA 94305 USA. Stanford Univ, Sch Med, Dept Pediat, Stanford, CA 94305 USA. Stanford Univ, Sch Med, Dept Hlth Res & Policy, Stanford, CA 94305 USA. NIDDKD, Phoenix Epidemiol & Clin Res Branch, Phoenix, AZ 85016 USA. RP Lemley, KV (reprint author), Stanford Univ, Sch Med, Div Pediat Nephrol, Dept Med, Stanford, CA 94305 USA. EM klemley@stanford.edu RI Nelson, Robert/B-1470-2012 FU NIBIB NIH HHS [5-R01-EB-002784-28]; NIDDK NIH HHS [1R01-DK-54600] NR 27 TC 13 Z9 14 U1 0 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 2005 VL 289 IS 4 BP F863 EP F870 DI 10.1152/ajprenal.00068.2004 PG 8 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 963VD UT WOS:000231833300023 PM 15900022 ER PT J AU Cohen, JR Elvevag, B Goldberg, TE AF Cohen, JR Elvevag, B Goldberg, TE TI Cognitive control and semantics in schizophrenia: An integrated approach SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT 42nd Meeting of the American-College-of-Neuropsychopharmacology CY DEC 07-11, 2003 CL San Juan, PR SP Amer Coll Neuropsychopharmacol ID ANTERIOR CINGULATE; CORTEX; MEMORY AB Objective: The authors tested whether decisions about incongruencies in the representation and processing of semantic knowledge, thought to be related to cognitive control, are selectively impaired in schizophrenia. Method: Twenty-four patients with schizophrenia and 24 healthy comparison subjects determined the relative size of paired stimuli as they are in the real world. Stimuli were words or images. Real-world "distance" (size difference between stimuli) was manipulated within pairs, as was "congruency" between real-world and presentation size. Results: Although patients were slower overall, both groups exhibited similar effects of "distance" and "congruency"; the task was easier when the real-world size difference between stimuli was greater and when stimuli were congruent in presentation and real-world size. Conclusions: Some aspects of the representation of semantic knowledge are preserved in schizophrenia, and patients use this information to control cognition in the same manner as healthy individuals. C1 NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. RP Elvevag, B (reprint author), NIMH, Clin Brain Disorders Branch, NIH, Bldg 10,Rm 4S235,MSC 139, Bethesda, MD 20892 USA. EM brita@elvevaag.net NR 11 TC 9 Z9 9 U1 2 U2 5 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 2005 VL 162 IS 10 BP 1969 EP 1971 DI 10.1176/appi.ajp.162.10.1969 PG 3 WC Psychiatry SC Psychiatry GA 969YJ UT WOS:000232271600026 PM 16199848 ER PT J AU Gorrindo, T Blair, RJR Budhani, S Dickstein, DP Pine, DS Leibenluft, E AF Gorrindo, T Blair, RJR Budhani, S Dickstein, DP Pine, DS Leibenluft, E TI Deficits on a probabilistic response-reversal task in patients with pediatric bipolar disorder SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID ORBITOFRONTAL CORTEX; RATING-SCALE; RELIABILITY; DYSFUNCTION; VALIDITY; CHILDREN; LESIONS AB Objective: Patients with bipolar disorder become hyperhedonic when manic and anhedonic when depressed; therefore, it is important to test whether patients with bipolar disorder show deficits on behavioral paradigms exploring reward/punishment mechanisms. Method: A probabilistic response-reversal task was administered to 24 bipolar children and 25 comparison subjects. Results: Patients made more errors during probabilistic reversal, took longer to learn the new reward object, and were less likely to meet the learning criterion. Conclusions: Children with bipolar disorder may have a reversal learning deficit. C1 NIMH, Mood & Anxiety Program, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. RP Leibenluft, E (reprint author), NIMH, Mood & Anxiety Program, Dept Hlth & Human Serv, NIH, Bldg 10,Rm 4N-208,10 Ctr Dr MSC 1255, Bethesda, MD 20892 USA. EM leibs@mail.nih.gov RI Dickstein, Daniel/L-3210-2016 OI Dickstein, Daniel/0000-0003-1647-5329 NR 12 TC 72 Z9 72 U1 0 U2 0 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 2005 VL 162 IS 10 BP 1975 EP 1977 DI 10.1176/appi.ajp.162.10.1975 PG 3 WC Psychiatry SC Psychiatry GA 969YJ UT WOS:000232271600028 PM 16199850 ER PT J AU Nabel, EG AF Nabel, EG TI Notes from the NHLBI director - Fostering the independence of new investigators SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Editorial Material C1 NHLBI, NIH, Bethesda, MD 20892 USA. RP Nabel, EG (reprint author), NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD OCT 1 PY 2005 VL 172 IS 7 BP 797 EP 797 DI 10.1164/rccm.2508003 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 967UD UT WOS:000232115800004 PM 16183712 ER PT J AU Busse, WW Wanner, A Adams, K Reynolds, HY Castro, M Chowdhury, B Kraft, M Levine, RJ Peters, SP Sullivan, EJ AF Busse, WW Wanner, A Adams, K Reynolds, HY Castro, M Chowdhury, B Kraft, M Levine, RJ Peters, SP Sullivan, EJ TI Investigative bronchoprovocation and bronchoscopy in airway diseases SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Review DE airway hyperresponsiveness; asthma; bronchoalveolar lavage; chronic obstructive pulmonary disease; lidocaine; methacholine; segmental allergen challenge ID BRONCHOALVEOLAR LAVAGE FLUID; OBSTRUCTIVE PULMONARY-DISEASE; SEGMENTAL ALLERGEN CHALLENGE; LATE ASTHMATIC RESPONSES; CYSTIC-FIBROSIS; FLEXIBLE BRONCHOSCOPY; BRONCHIAL HYPERRESPONSIVENESS; ANTIGEN CHALLENGE; CELL PROFILES; FIBEROPTIC BRONCHOSCOPY AB Rationale: Basic and clinical research strategies used for many lung diseases have depended on volunteer subjects undergoing bronchoscopy to establish access to the airways to collect biological specimens and tissue, perhaps with added bronchoprovocation in asthma syndromes. These procedures have yielded a wealth of important scientific information. Since the last critical review more than a decade ago, some of the techniques and applications have changed, and untoward events have occurred, raising safety concerns and increasing institutional review scrutiny. Objectives and Methods: To reappraise these investigational methods in the context of current knowledge, the National Heart, Lung, and Blood Institute and the National Institute of Allergy and Infectious Diseases of the National Institutes of Health convened a working group to review these procedures used for airway disease research, emphasizing asthma and chronic obstructive pulmonary disease. Main Results: The group reaffirmed the scientific importance of investigative bronchoscopy and bronchoprovocation, even as less invasive technologies evolve. The group also considered the safety of bronchoscopy and bronchoprovocation with methacholine and, antigen to be acceptable for volunteer subjects and patients, but stressed the need to monitor this closely and to emphasize proper training of participating medical research personnel. Issues were raised about vulnerable volunteers, especially children who need surrogates for informed consent. Conclusion: This review of investigative bronchoscopy and bronchoprovocation could serve as the basis for future guidelines for the use of these procedures in the United States. C1 NHLBI, DLD, Bethesda, MD 20892 USA. Univ Wisconsin, Madison, WI USA. NIAID, Bethesda, MD USA. US FDA, Rockville, MD USA. Washington Univ, Sch Med, St Louis, MO USA. Natl Jewish Med & Res Ctr, Denton, CO USA. Yale Univ, Sch Med, New Haven, CT USA. Wake Forest Univ, Hlth Sci, Winston Salem, NC USA. Miami Univ, Sch Med, Miami, FL USA. RP Reynolds, HY (reprint author), NHLBI, DLD, 2 Rockledge Ctr,6701 Rockledge Dr, Bethesda, MD 20892 USA. EM reynoldh@mail.nih.gov NR 111 TC 48 Z9 50 U1 0 U2 0 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 2005 VL 172 IS 7 BP 807 EP 816 DI 10.1164/rccm.200407-966WS PG 10 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 967UD UT WOS:000232115800006 PM 16020805 ER PT J AU Montoya, ID Herbeck, DM Svikis, DS Pincus, HA AF Montoya, ID Herbeck, DM Svikis, DS Pincus, HA TI Identification and treatment of patients with nicotine problems in routine clinical psychiatry practice SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article; Proceedings Paper CT 9th Annual Meeting of the Society-for-Research-on-Nicotine-and-Tobacco CY FEB 19-22, 2003 CL NEW ORLEANS, LA SP Soc Res Nicotine & Tobacco ID SMOKING-CESSATION TREATMENT; MENTAL-ILLNESS; CIGARETTE-SMOKING; UNITED-STATES; PREVALENCE; DEPENDENCE; POPULATION; SCHIZOPHRENIA; DISORDERS; TRENDS AB The aim of this study is to assess the rates of nicotine problems diagnosed by psychiatrists, the characteristics of psychiatric patients who smoke, and the services provided to them in routine psychiatric practice. Data were obtained by asking psychiatrists participating in the American Psychiatric Institute for Psychiatric Research and Education's Practice Research Network to complete a self-administered questionnaire to provide detailed sociodemographic, clinical, and health plan information on three of their patients seen during routine clinical practice. A total of 615 psychiatrists provided information on 1,843 patients, of which 280 (16.6%) were reported to have a current nicotine problem. Of these, 9.1% were reported to receive treatment for nicotine dependence. Patients with nicotine problems were significantly more likely to be males, divorced or separated, disabled, and uninsured, and have fewer years of education. They also had significantly more co-morbid psychiatric disorders, paiticularly schizophrenia or alcohol/ substance use disorders; a lower Global Assessment Functioning score; and poorer treatment compliance than their counterparts. The results suggest a very low rate of identification and treatment of nicotine problems among patients treated by psychiatrists, even though psychiatric patients who smoke seem to have more clinical and psychosocial stressois and more severe psychiatric problems than those who do not smoke. C1 NIDA, Div Pharmacotherapies & Med Consequences Drug Abu, Bethesda, MD 20892 USA. Amer Psychiat Inst Psychiat Res & Educ, Practice Res Network, Santa Monica, CA USA. Virginia Commonwealth Univ, Dept Psychol, Richmond, VA 23284 USA. Western Psychiat Inst & Clin, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. RAND, Pittsburgh, PA USA. RP Montoya, ID (reprint author), NIDA, Div Pharmacotherapies & Med Consequences Drug Abu, 6001 Execut Blvd, Bethesda, MD 20892 USA. EM imontoya@mail.nih.gov FU Intramural NIH HHS [Z99 DA999999] NR 28 TC 31 Z9 31 U1 1 U2 2 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PD OCT-DEC PY 2005 VL 14 IS 5 BP 441 EP 454 DI 10.1080/10550490500247123 PG 14 WC Substance Abuse SC Substance Abuse GA 988LC UT WOS:000233601700004 PM 16257881 ER PT J AU Parloff, MB Shapiro, DL AF Parloff, MB Shapiro, DL TI Jerome D Frank (1910-2005) - Obituary SO AMERICAN PSYCHOLOGIST LA English DT Biographical-Item C1 NIMH, Bethesda, MD 20892 USA. Harvard Univ, Cambridge, MA 02138 USA. RP Parloff, MB (reprint author), NIMH, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER PSYCHOLOGICAL ASSOC/EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0003-066X J9 AM PSYCHOL JI Am. Psychol. PD OCT PY 2005 VL 60 IS 7 BP 727 EP 727 DI 10.1037/0003-066X.60.7.727 PG 1 WC Psychology, Multidisciplinary SC Psychology GA 973UQ UT WOS:000232548500005 PM 16221005 ER PT J AU Lokuta, MA Cooper, KM Aksentijevich, I Kastner, DL Huttenlocher, A AF Lokuta, MA Cooper, KM Aksentijevich, I Kastner, DL Huttenlocher, A TI Neutrophil chemotaxis in a patient with neonatal-onset multisystem inflammatory disease and Muckle-Wells syndrome SO ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY LA English DT Article ID FAMILIAL MEDITERRANEAN FEVER; ARTICULAR SYNDROME; COLD URTICARIA; MUTATIONS; PROTEIN; PYRIN; CIAS1; GENE; MANIFESTATIONS; DISORDERS AB Background: Neonatal-onset multisystem inflammatory disease (NOMID)/chronic infantile neurologic, cutaneous, and articular syndrome is an autoinflammatory disease characterized by urticarial rash, arthropathy, and central nervous system inflammation. Objective: To describe a 13-year-old girl with overlapping symptoms of NOMID and Muckle-Wells syndrome who has a mutation in cryopyrin (NALP3). Methods: We examined neutrophil migration using transwell assay and time-lapse videomicroscopy. We also examined p38 mitogen-activated protein kinase (MAPK) activation in patient and control neutrophils using Western blot analysis. Results: Neutrophil defects in chemotactic migration were found to a variety of chemoattractants, including interleukin 8, N-formyl-methionyl-leucyl-phenylalanine, complement C5a, and leukotriene B-4. Her neutrophils exhibited elevated basal and stimulated p38 MAPK activation in response to interleukin 8, N-formyl-methionyl-leucyl-phenylalanine, complement C5a, and leukotriene B-4. Conclusions: This study is the first, to our knowledge, to demonstrate defects in neutrophil chemotaxis and p38 MAPK signaling in a patient with NOMID and Muckle-Wells syndrome and a cryopyrin mutation. C1 Univ Wisconsin, Sch Med, Dept Pediat, Madison, WI 53706 USA. Univ Wisconsin, Sch Med, Cellular & Mol Biol Program, Madison, WI 53706 USA. NIAMSD, NIH, Bethesda, MD 20892 USA. Univ Wisconsin, Sch Med, Dept Pharmacol, Madison, WI 53706 USA. RP Huttenlocher, A (reprint author), Univ Wisconsin, Sch Med, Dept Pediat, 3770 MSC,1300 Univ Ave, Madison, WI 53706 USA. EM huttenlocher@wisc.edu FU NIAID NIH HHS [1P01-AI50500-01] NR 24 TC 9 Z9 11 U1 1 U2 1 PU AMER COLL ALLERGY ASTHMA IMMUNOLOGY PI ARLINGTON HTS PA 85 WEST ALGONQUIN RD SUITE 550, ARLINGTON HTS, IL 60005 USA SN 1081-1206 J9 ANN ALLERG ASTHMA IM JI Ann. Allergy Asthma Immunol. PD OCT PY 2005 VL 95 IS 4 BP 394 EP 399 PG 6 WC Allergy; Immunology SC Allergy; Immunology GA 975YK UT WOS:000232699800017 PM 16279571 ER PT J AU Spring, B Pagoto, S Kaufmann, PG Whitlock, EP Glasgow, RE Smith, TW Trudeau, KJ Davidson, KW AF Spring, B Pagoto, S Kaufmann, PG Whitlock, EP Glasgow, RE Smith, TW Trudeau, KJ Davidson, KW TI Invitation to a dialogue between researchers and clinicians about evidence-based behavioral medicine SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Review ID EMPIRICALLY VALIDATED TREATMENTS; CORONARY-HEART-DISEASE; OF-LIFE ASSESSMENT; SMOKING-CESSATION; RANDOMIZED-TRIALS; SUPPORTED TREATMENTS; PREVENTIVE-SERVICES; REPLACEMENT THERAPY; HEALTH PSYCHOLOGY; TREATMENT MANUALS AB Background. Evidence-based behavioral medicine (EBBM) aims to improve the process through which best scientific research evidence can be obtained and translated into best clinical decisions regarding behavioral treatments to improve health. Purpose: The objective was to examine some legitimate concerns raised by both clinicians and researchers about the evidence-based movement. Methods: This article begins with a discussion of clinicians' fears that EBBM devalues clinical judgment and the therapist-patient relationship, will be used to restrict practice, is unnecessary, and is based on research that is irrelevant to clinical decision making. Next we consider researchers' worries that EBBM neglects evidence not based on randomized controlled trials and ignores causal mechanisms. Results: We find that these fears, although understandable, largely reflect misinterpretations of the evidence-based movement. Further it is suggested that behavioral medicine is in a unique position to enhance the evidence-based movement by encouraging increased attention to treatment mechanisms and to knowledge translation. Conclusions: Clinicians, researchers, and, importantly, the public will benefit from the evidence-based movement by having a health care system that is built on solid grounds of evidence in determining which treatments should constitute the standard of care. A full partnership between clinicians and researchers is called for to generate the practical, rigorous evidence base needed to take behavioral health treatments to the next level of scientific support and implementation. C1 Edward Hines Jr Vet Adm Hosp, Chicago, IL 60607 USA. NHLBI, Bethesda, MD 20892 USA. Univ Utah, Salt Lake City, UT 84112 USA. CUNY, Grad Ctr, New York, NY 10021 USA. Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. RP Spring, B (reprint author), Univ Illinois, Dept Psychol, M-C 285,1007 W Harrison St, Chicago, IL 60607 USA. EM bspring@uic.edu RI Pagoto, Sherry/L-2014-2013 OI Pagoto, Sherry/0000-0002-2462-8797 NR 102 TC 31 Z9 31 U1 2 U2 3 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PD OCT PY 2005 VL 30 IS 2 BP 125 EP 137 DI 10.1207/s15324796abm3002_5 PG 13 WC Psychology, Multidisciplinary SC Psychology GA 972CM UT WOS:000232431600005 PM 16173909 ER PT J AU Colt, JS Wacholder, S Schwartz, K Davis, F Graubard, B Chow, WH AF Colt, JS Wacholder, S Schwartz, K Davis, F Graubard, B Chow, WH TI Response rates in a case-control study: Effect of disclosure of biologic sample collection in the initial contact letter SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE data collection; epidemiologic methods; epidemiologic research design; response rates AB PURPOSE: Participants in epidemiology studies are often asked to complete an interview and to provide biospecimens. In a population-based case-control study of kidney cancer involving an interview and optional biospecimens, we examined whether mentioning the biospecimens in the initial contact letter adversely affects willingness to be interviewed. METHODS: Eligible cases (n = 434) and controls (n = 775) in Detroit were alternately assigned to receive one of two versions of the contact letter. Both explained that the study involves an interview with $100 compensation plus an optional component with additional compensation; only one disclosed that the optional component involved biospecimens. RESULTS: There were no meaningful differences between the groups in willingness to be interviewed. However, among 303 cases and 351 controls already interviewed, the proportion providing biospecimens was higher in the fully informed group: for blood, the differences were 10.8 (95% CI, 2.0, 19.5) for cases and 6.7% (95% CI, -1.7, 15. 1) for controls. Findings were similar for saliva. CONCLUSIONS: In a study involving an interview and optional biospecimens, informing people about the samples in the contact letter seems preferable to a non-specific reference to a second study component. Both approaches yielded similar interview participation rates, but biospecimen participation rates were higher among those informed about the samples in the contact letter. C1 NCI, Div Canc Epdiemiol & Genet, Dept Hlth & Human Serv, NIH, Bethesda, MD USA. Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. Wayne State Univ, Dept Family Med, Detroit, MI USA. Univ Illinois, Sch Publ Hlth, Div Epidemiol & Biostat, Chicago, IL USA. RP Colt, JS (reprint author), Natl Canc Inst, Occupat Epidemiol Branch, 6120 Execut Blvd,Room 8112, Rockville, MD 20852 USA. EM coltj@mail.nih.gov NR 3 TC 4 Z9 4 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD OCT PY 2005 VL 15 IS 9 BP 700 EP 704 DI 10.1016/j.annepidem.2004.12.002 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 969NF UT WOS:000232240200005 PM 16157256 ER PT J AU Andrieu, N Dondon, MG Goldstein, AM AF Andrieu, N Dondon, MG Goldstein, AM TI Increased power to detect gene-environment interaction using siblings controls SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE case-control study; G X E interaction; sibling controls; study design; conditional analysis; unconditional analysis ID SAMPLE-SIZE REQUIREMENTS; POPULATION STRATIFICATION; ASCERTAINMENT BIAS; DESIGN; ASSOCIATION; EFFICIENCY; CANCER; STRATEGIES; EXPOSURE; JOINT AB PURPOSE: Interest is increasing in studying gene-environment (G X E) interaction in disease etiology. Study designs using related controls as a more appropriate control group for evaluating 0 X E interactions have been proposed but often assume unrealistic numbers of available relative controls. To evaluate a more realistic design, we studied the relative efficiency of a 1:0.5 case-sibling-control design compared with a classical 1:1 case-unrelated-control design and examined the effect of the analysis strategy. METHODS: Simulations were performed to assess the efficiency of a 1:0.5 case-sibling-controt design relative to a classical 1: 1 case-unrelated-control design under a variety of assumptions for estimating G X E interaction. Both matched and unmatched analysis strategies were examined. RESULTS: When using a matched analysis, the 1: 1 case-unrelated-control design was almost always more powerful than the 1:0.5 case-sibling-control design. In contrast, when using an unmatched analysis, the 1:0.5 case-sibling-control design was almost always more powerful than the 1:1 case-unrelated-control design. The unconditional analysis of the case-sibling-control design to estimate G X E interaction, however, requires no correlation in E between siblings. CONCLUSIONS: In most settings, a matched analysis may be required and a 1: 1 case-unrelated-control design will be more powerful than a 1:0.5 case-sibling-control design. C1 Nalt Inst Hlth & Med Res EMI00 06, Evry, France. Inst Curie, Natl Inst Hlth & Med Res ICI10213, Biostat Unit, Paris, France. NCI, Genet Epidemiol Branch, Div Canc Epidmeiol & Genet, DHHS,NIH, Bethesda, MD USA. RP Andrieu, N (reprint author), Inst Curie, INSERM, Serv Biostat, EM100 06, F-75248 Paris 05, France. EM nadine.andrieu@curie.net RI ANDRIEU, Nadine/H-4255-2014 NR 27 TC 3 Z9 3 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD OCT PY 2005 VL 15 IS 9 BP 705 EP 711 DI 10.1016/j.annepidem.2005.01.002 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 969NF UT WOS:000232240200006 PM 16157257 ER PT J AU Biasco, G Sassatelli, R Nobili, E Camellini, L Pantaleo, MA Bertoni, G Calabrese, C De Vivo, A Poggioli, G De Leon, MP Bedogni, G Venesio, T Varesco, L Risio, M Di Febo, G Brandi, G AF Biasco, G. Sassatelli, R. Nobili, E. Camellini, L. Pantaleo, M. A. Bertoni, G. Calabrese, C. De Vivo, A. Poggioli, G. De Leon, M. Ponz Bedogni, G. Venesio, T. Varesco, L. Risio, M. Di Febo, G. Brandi, G. TI The risk of duodenal cancer in familial adenomatous polyposis (FAP) SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract C1 Univ Bologna, Inst Haematol & Med Oncol L & A Seranogli, I-40126 Bologna, Italy. Univ Bologna, Dept Gastroenterol & Internal Med, I-40126 Bologna, Italy. Santa Maria Nuova Hosp, Gastrointestinal Endoscopy Unit, Reggio Emilia, Italy. Univ Modena, Natl Canc Inst, Dept Internal Med, I-41100 Turin, Italy. Natl Canc Inst, Genoa, Italy. RI Ponz de Leon, Maurizio/A-9356-2015 OI Ponz de Leon, Maurizio/0000-0003-4465-1043 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 2005 VL 16 SU 7 BP 50 EP 50 PG 1 WC Oncology SC Oncology GA V43YI UT WOS:000202970000183 ER PT J AU Pollera, CF Pessina, G Cianciulli, A Gallucci, M Sentinelli, S Mottolese, M Ruggeri, E Giannarelli, D Felici, A Nelli, F Muto, G Boccardo, F Cognetti, F AF Pollera, C. F. Pessina, G. Cianciulli, A. Gallucci, M. Sentinelli, S. Mottolese, M. Ruggeri, E. Giannarelli, D. Felici, A. Nelli, F. Muto, G. Boccardo, F. Cognetti, F. TI Preliminary cytogenetic and pharmacogenomic analysis of invasive bladder cancer in the Italian adjuvant trial comparing cisplatin-gemcitabine (PG) vs observation (OBS) after radical cystectomy SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract C1 Belcolle Hosp, Viterbo, Italy. Univ Tuscia, Viterbo, Italy. Regina Elena Inst Canc Res, Rome, Italy. G Bosco Hosp, Turin, Italy. Natl Canc Inst, Genoa, Italy. 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 2005 VL 16 SU 7 BP 83 EP 83 PG 1 WC Oncology SC Oncology GA V43YI UT WOS:000202970000324 ER PT J AU Drgon, T Saito, K Gillevet, PM Sikaroodi, M Vasta, GR AF Drgon, T Saito, K Gillevet, PM Sikaroodi, M Vasta, GR TI Characterization of Pfiesteria ichthyocidal activity - Authors' reply SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Letter ID AMBUSH-PREDATOR DINOFLAGELLATE; TOXIC PFIESTERIA; PISCICIDA; FISH; BIOASSAY; CULTURE; STRAINS C1 NIA, Baltimore, MD 21224 USA. Univ Maryland, Biotechnol Inst, Ctr Marine Biotechnol, Baltimore, MD 21202 USA. George Mason Univ, Dept Environm Sci & Policy, Manassas, VA 20110 USA. Univ Maryland, Biotechnol Inst, Ctr Marine Biotechnol, Baltimore, MD 21202 USA. RP Drgon, T (reprint author), NIA, Baltimore, MD 21224 USA. EM vasta@umbi.umd.edu NR 11 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 EI 1098-5336 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD OCT PY 2005 VL 71 IS 10 BP 6464 EP 6464 PG 1 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 973DV UT WOS:000232504000109 ER PT J AU Murray, IA Reen, RK Leathery, N Ramadoss, P Bonati, L Gonzalez, FJ Peters, JM Perdew, GH AF Murray, IA Reen, RK Leathery, N Ramadoss, P Bonati, L Gonzalez, FJ Peters, JM Perdew, GH TI Evidence that ligand binding is a key determinant of Ah receptor-mediated transcriptional activity SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE Ah receptor; ARNT; TCDD; dioxin; modeling; AhR; photoaffinity ligand; bHLH-PAS; iodoflavone; simian virus 40; immortalization ID ARYL-HYDROCARBON RECEPTOR; X-ASSOCIATED PROTEIN-2; CELL-CYCLE CONTROL; MONOCLONAL-ANTIBODIES; NUCLEAR TRANSLOCATOR; EPITHELIAL-CELLS; DIOXIN RECEPTOR; HEPATOMA-CELLS; CORE COMPLEX; DNA-BINDING AB The aryl hydrocarbon receptor (AhR) mediates the biological activity of 2,3,7,8 -tetrachlorodibenzo-p-dioxin. Whether the AhR can mediate enhanced transcriptional activity in the absence of ligand binding has not been established. Hepatocytes from AhR-null (AhR-KO) and wild-type (AhR-WT) neonatal mice were immortalized with Simian virus 40. Two point mutants of the AhR, A375I and A375F, were generated to test the hypothesis that the AhR requires ligand binding to exhibit significant transcriptional activity, both mutants fail to bind ligand or exhibit enhanced activity in cells exposed to AhR ligands. Upon transient, co-expression of ARNT with AhR-A375I or AhR-A375F in AhR-KO cells, these mutants exhibited significant ligand-independent transcriptional activity. However, in CV-1 cells, which others have previously shown to contain relatively high levels of AhR ligand(s), these AhR mutants exhibit essentially no constitutive activity. These results indicate that while the AhR can potentially exhibit activity in the absence of ligand binding, the high constitutive receptor activity observed in many cell lines appears to be due to the presence of endogenous AhR ligands. (c) 2005 Elsevier Inc. All rights reserved. C1 Penn State Univ, Ctr Mol Toxicol & Carcinogenesis, University Pk, PA 16802 USA. Penn State Univ, Dept Vet Sci, University Pk, PA 16802 USA. Univ Milan, Dipartimento Sci Ambiente & Terr, Milan, Italy. NCI, Lab Metab, Bethesda, MD 20892 USA. RP Perdew, GH (reprint author), Penn State Univ, Ctr Mol Toxicol & Carcinogenesis, University Pk, PA 16802 USA. EM ghp2@psu.edu RI Peters, Jeffrey/D-8847-2011 FU NIEHS NIH HHS [ES011834, ES04869] NR 41 TC 26 Z9 26 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD OCT 1 PY 2005 VL 442 IS 1 BP 59 EP 71 DI 10.1016/j.abb.2005.07.014 PG 13 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 970ME UT WOS:000232313500007 PM 16137638 ER PT J AU Suppes, T Mintz, J McElroy, SL Altshuler, LL Kupka, RW Frye, MA Keck, PE Nolen, WA Leverich, GS Grunze, H Rush, AJ Post, RM AF Suppes, T Mintz, J McElroy, SL Altshuler, LL Kupka, RW Frye, MA Keck, PE Nolen, WA Leverich, GS Grunze, H Rush, AJ Post, RM TI Mixed hypomania in 908 patients with bipolar disorder evaluated prospectively in the Stanley Foundation Bipolar Treatment Network - A sex-specific phenomenon SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 4th European-Stanley-Foundation Conference on Bipolar Disorder CY SEP 23-24, 2004 CL Aarhus, DENMARK SP European Stanley Fdn ID PROSPECTIVE FOLLOW-UP; DYSPHORIC MANIA; DEPRESSIVE SYMPTOMATOLOGY; CLINICAL CHARACTERISTICS; STATES; EPISODE; LITHIUM; GENDER; PREVALENCE; INVENTORY AB Context: The prevalence of depressive symptoms co-occurring with hypomanic symptoms has not been quantified. Whether there is a greater likelihood for women to experience mixed symptoms has not been resolved. Objectives: To determine whether mixed hypomania is observed more frequently than euphoric hypomania and whether a sex effect exists in patients with bipolar disorder. Setting: Academic research settings in the United States (4 sites) and Europe (3 sites). Participants: Subjects were enrolled in a naturalistic prospective study after providing written informed consent. Main Outcome Measures: Mixed hypomania was defined at a given visit as a Young Mania Rating Scale score of 12 or higher and an Inventory of Depressive Symptomatology-Clinician-Rated Version score of 15 or higher. Given partial overlap of items from these scales, exploratory analyses were completed assessing instrument overlap affecting the findings. Results: In 908 patients, 14 328 visits over 7 years were evaluated. Patients with bipolar I disorder were significantly more likely to experience hypomania than those with bipolar 11 disorder. Of all 1044 visits by patients with hypomanic symptoms, 57% met criteria for mixed hypomania. The likelihood of depression was significantly greater for women during hypomania (P <.001). For women, the probability of mixed symptoms increased with the severity of hypomania and then decreased at the most severe levels of hypomania or mania. When a modified Inventory of Depressive Symptomatology Clinician-Rated Version was evaluated by removing the 5 overlapping Young Mania Rating Scale items, a significant sex effect persisted for women (P <.001) but not for men (P=.95),owing to the elimination of the items "irritability" and "agitation." Conclusions: Mixed hypomania is common in patients with symptoms of hypomania and particularly common in women. Potential overlap of clinical symptom scales should be assessed before study of patients with bipolar disorder symptoms is undertaken. C1 Univ Texas, SW Med Ctr, Dept Psychiat, Bipolar Disorder Res Program, Dallas, TX 75390 USA. Univ Calif Los Angeles, Inst Neuropsychiat, Biostat Core, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Mood Disorder Clin, Los Angeles, CA USA. Univ Cincinnati, Coll Med, Dept Psychiat, Psychopharmacol Res Program, Cincinnati, OH USA. Altrecht Inst Mental Hlth Care, Utrecht, Netherlands. Cincinnati Vet Affairs Med Ctr, Gen Clin Res Ctr & Mental Hlth Care Line, Cincinnati, OH USA. Univ Groningen Hosp, Dept Psychiat, Groningen, Netherlands. NIMH, Biol Psychiat Branch, NIH, Bethesda, MD 20892 USA. Univ Munich, Dept Psychiat, D-8000 Munich, Germany. RP Suppes, T (reprint author), Univ Texas, SW Med Ctr, Dept Psychiat, Bipolar Disorder Res Program, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM trisha.suppes@utsouthwestern.edu RI Nolen, Willem/E-9006-2014; Mintz, Jim/N-7385-2014; OI Mintz, Jim/0000-0002-8299-5851; Rush, Augustus/0000-0003-2004-2382 FU NIMH NIH HHS [R01 MH079261] NR 46 TC 118 Z9 120 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD OCT PY 2005 VL 62 IS 10 BP 1089 EP 1096 DI 10.1001/archpsyc.62.10.1089 PG 8 WC Psychiatry SC Psychiatry GA 972CD UT WOS:000232430600004 PM 16203954 ER PT J AU Hasin, DS Goodwin, RD Stinson, FS Grant, BF AF Hasin, DS Goodwin, RD Stinson, FS Grant, BF TI Epidemiology of major depressive disorder - Results from the National Epidemiologic Survey on Alcoholism and Related Conditions SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID DSM-III-R; PSYCHIATRIC RESEARCH INTERVIEW; CLINICAL-SIGNIFICANCE CRITERION; GENERAL-POPULATION SAMPLE; SUBSTANCE USE DISORDERS; MENTAL-HEALTH SURVEY; UNITED-STATES; PERSONALITY-DISORDERS; COMORBIDITY-SURVEY; IV ALCOHOL AB Objective: To present nationally representative data on 12-month and lifetime prevalence, correlates, and co-morbidity of DSM-IV major depressive disorder (MDD) among adults in the United States. Design/Setting/Parlicipants: Face-to-face survey of more than 43 000 adults aged 18 years and older residing in households and group quarters in the United States. Main Outcome Measures: Prevalence and associations of MDD with sociodemographic correlates and Axis I and II disorders. Results: The prevalence of 12-month and lifetime DSM-IV MDD was 5.28% (95% confidence interval, 4.98-5.57) and 13.23% (95% confidence interval, 12.64-13.81), respectively. Being female; Native American; middle-aged; widowed, separated, or divorced; and low income increased risk, and being Asian, Hispanic, or black decreased risk (P <.05). Women were significantly more likely to receive treatment than men. Both current and lifetime MDD were significantly associated with other specific psychiatric disorders, notably substance dependence, panic and generalized anxiety disorder, and several personality disorders. Conclusions: This large survey suggests a higher prevalence of MDD in the US population than large-sample estimates from the 1980s and 1990s. The shift in highest lifetime risk from young to middle-aged adults is an important transformation in the distribution of MDD in the United States and specificity in risk for an age-period cohort. Associations between MDD and Axis I and II disorders were strong and significant, with variation within broad categories by specific diagnoses signaling the need for attention to the genetic and environmental reasons for such variation, as well as the implications for treatment response. C1 NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, Bethesda, MD 20892 USA. Columbia Univ, Mailman Sch Publ Hlth, Div Epidemiol, New York, NY USA. Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY USA. New York State Psychiat Inst & Hosp, New York, NY 10032 USA. RP Grant, BF (reprint author), NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, Room 3077, Bethesda, MD 20892 USA. EM bgrant@willco.niaaa.nih.gov FU NIAAA NIH HHS [R01AA08159, K05AA00161] NR 99 TC 795 Z9 820 U1 12 U2 69 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD OCT PY 2005 VL 62 IS 10 BP 1097 EP 1106 DI 10.1001/archpsyc.62.10.1097 PG 10 WC Psychiatry SC Psychiatry GA 972CD UT WOS:000232430600005 PM 16203955 ER PT J AU Zhou, ZF Roy, A Lipsky, R Kuchipudi, K Zhu, GS Taubman, J Enoch, MA Virkkunen, M Goldman, D AF Zhou, ZF Roy, A Lipsky, R Kuchipudi, K Zhu, GS Taubman, J Enoch, MA Virkkunen, M Goldman, D TI Haplotype-based linkage of tryptophan hydroxylase 2 to suicide attempt, major depression, and cerebrospinal fluid 5-hydroxyindoleacetic acid in 4 populations SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID TRYPTOPHAN-HYDROXYLASE GENE; SEROTONIN TRANSPORTER; MONOAMINE METABOLITES; TPH2 GENE; POLYMORPHISM; ASSOCIATION; BEHAVIOR; MUTATION; ISOFORM; TRAITS AB Context: Tryptophan hydroxylase 2 (TPH2) encodes the rate-limiting enzyme for brain serotonin biosynthesis. It was recently reported that the TPH2 haplotype was linked to depression in humans. Objective: To determine the association of TPH2 with suicide attempt, major depression, and a neurochemical intermediate phenotype, cerebrospinal fluid 5-hydroxyindoleacetic acid. Design: We resequenced TPH2 coding, 5' promoter, 3'-untranslated region, and splice junction regions in 190 individuals selected for ethnic and clinical diversity, determined haplotype structure using 15 single nucleotide polymorphisms spanning 106 kilobases (kb), and performed linkage analysis in 1798 cases and controls representing 4 populations (657 African Americans, including 104 suicide attempters and 135 with major depression; 513 Finnish whites, including 150 suicide attempters; 146 US whites, including 81 with depression, anxiety disorder, or both; and 482 southwestern American Indians, including 123 suicide attempters and 191 with depression, anxiety disorder, or both) and in 94 Finnish whites for cerebrospinal fluid 5-hydroxyindoleacetic acid levels. Results: Sixteen single nucleotide polymorphisms, including Pro206Ser, were detected. The 15-locus panel defined and maximized information content from 2 haplotype blocks in whites, 3 haplotype blocks in African Americans, and the single haplotype block spanning TPH2 in southwestern American Indians. Among common Block1b haplotypes were 2 in yin and yang (opposite) configuration,. indicating ancient origin. The yin haplotype, 212121, was increased in frequency in suicide attempters in both populations tested (Finnish whites and African Americans). It was associated with major depression and anxiety disorders in US whites and with major depression in African Americans. The yin haplotype was moderately predictive of lower cerebrospinal fluid 5-hydroxyindoleacetic acid concentrations in controls but not in cases. Conclusion: Haplotype linkage of TPH2 to suicide attempt and major depression and to a mediating phenotype, cerebrospinal fluid 5-hydroxyindoleacetic acid, provides preliminary evidence of a functional locus potentially within a haplotype block at least 52 kb in size. C1 NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA. Dept Vet Affairs, New Jersey Hlth Care Syst, E Orange, NJ USA. Univ Helsinki, Dept Psychiat, SF-00180 Helsinki, Finland. RP Goldman, D (reprint author), NIAAA, Neurogenet Lab, NIH, 5625 Fishers Ln,Room 3S32, Rockville, MD 20852 USA. EM dgneuro@mail.nih.gov RI Goldman, David/F-9772-2010; OI Goldman, David/0000-0002-1724-5405; Lipsky, Robert/0000-0001-7753-1473 NR 37 TC 148 Z9 153 U1 0 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD OCT PY 2005 VL 62 IS 10 BP 1109 EP 1118 DI 10.1001/archpsyc.62.10.1109 PG 10 WC Psychiatry SC Psychiatry GA 972CD UT WOS:000232430600006 PM 16203956 ER PT J AU Kollins, SH McClernon, FJ Fuemmeler, BF AF Kollins, SH McClernon, FJ Fuemmeler, BF TI Association between smoking and attention-deficit/hyperactivity disorder symptoms in a population-based sample of young adults SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID DEFICIT HYPERACTIVITY DISORDER; SUBSTANCE USE DISORDERS; UTAH RATING-SCALE; CIGARETTE-SMOKING; EARLY ADOLESCENCE; RESEARCH CRITERIA; CHILDREN; ADHD; RELIABILITY; CHILDHOOD AB Context: Attention-deficit/hyperactivity disorder (ADHD) has been associated with increased risk of smoking, and some studies have suggested that inattentive symptoms specifically may underlie this risk. Few studies, however, have examined ADHD symptoms in nonclinical samples to determine the extent to which the number of symptoms-independent of the full diagnosis-confer risk for smoking-related outcomes. Objective: To evaluate the relation between. smoking-related variables and the number of retrospectively reported ADHD inattentive and hyperactive/impulsive symptoms in a population-based sample of young adults. Design, Setting, and Participants: The study population consists of 15 197 eligible participants from wave III of the National Longitudinal Study of Adolescent Health, a nationally representative sample of adolescents followed from 1995 to 2002. Main Outcome Measures: Logistic regression was used to examine the relation between self-reported ADHD symptoms and the lifetime likelihood of being a regular smoker, defined by having smoked at least 1 cigarette a day for 30 days. For individuals reporting regular smoking, we also examined the extent to which ADHD symptoms predicted age at onset of regular smoking and number of cigarettes smoked. Results: A linear relation was identified between the number of self-reported inattentive and hyperactive/impulsive symptoms and smoking outcome measures (P <.001 for each symptom domain). Controlling for demographic and conduct disorder symptoms, each reported inattention and hyperactivity/impulsivity symptom significantly increased the likelihood of ever regular smoking (odds ratio [OR], 1.11; 95% confidence interval [CI], 1.08-1.14 and OR, 1.16; 95% CI, 1.131.19, respectively). For those reporting lifetime regular smoking, reported symptoms decreased the estimated age at onset and increased the number of cigarettes smoked. Conclusions: Self-reported ADHD symptoms were found to be associated with adult smoking outcome variables in this nationally representative sample, providing further evidence of a likely link between ADHD symptoms and risk for tobacco use. C1 Duke Univ, Med Ctr, Durham, NC USA. NCI, Bethesda, MD 20892 USA. RP Kollins, SH (reprint author), ADHD Program, 718 Rutherford St, Durham, NC 27705 USA. EM kolli001@mc.duke.edu RI Kollins, Scott/G-2965-2012 FU NICHD NIH HHS [P01-HD31921]; NIDA NIH HHS [K23DA017261-01] NR 37 TC 186 Z9 189 U1 7 U2 13 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD OCT PY 2005 VL 62 IS 10 BP 1142 EP 1147 DI 10.1001/archpsyc.62.10.1142 PG 6 WC Psychiatry SC Psychiatry GA 972CD UT WOS:000232430600009 PM 16203959 ER PT J AU Petry, NM Peirce, JM Stitzer, ML Blaine, J Roll, JM Cohen, A Obert, J Killeen, T Saladin, ME Cowell, M Kirby, KC Sterling, R Royer-Malvestuto, C Hamilton, J Booth, RE Macdonald, M Liebert, M Rader, L Burns, R DiMaria, J Copersino, M Stabile, PQ Kolodner, K AF Petry, NM Peirce, JM Stitzer, ML Blaine, J Roll, JM Cohen, A Obert, J Killeen, T Saladin, ME Cowell, M Kirby, KC Sterling, R Royer-Malvestuto, C Hamilton, J Booth, RE Macdonald, M Liebert, M Rader, L Burns, R DiMaria, J Copersino, M Stabile, PQ Kolodner, K TI Effect of prize-based incentives on outcomes in stimulant abusers in outpatient psychosocial treatment programs - A national drug abuse treatment clinical trials network study SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 66th Annual Meeting of the College-on-Problems-of-Drug-Dependence CY JUN 14, 2004 CL San Juan, PR SP Coll Problems Drug Dependence ID COCAINE-DEPENDENT OUTPATIENTS; REINFORCEMENT CONTINGENCY MANAGEMENT; METHADONE-MAINTENANCE PATIENTS; FOLLOW-UP OUTCOMES; BEHAVIORAL TREATMENT; TREATMENT RETENTION; ALCOHOL DEPENDENCE; ABSTINENCE; DATOS; THERAPY AB Context: Contingency management interventions that provide tangible incentives based on objective indicators of drug abstinence are efficacious in improving outcomes in substance abusers, but these treatments have rarely been implemented, in community-based settings. Objective: To evaluate the efficacy of an abstinence-based contingency management intervention as an addition to usual care in community treatment settings. Design: Random assignment to usual care or usual care plus abstinence-based incentives for 12 weeks. Setting: Eight community-based outpatient psychosocial drug abuse treatment programs. Participants: A total of 415 cocaine or methamphetamine users beginning outpatient substance abuse treatment. Intervention: All participants received standard care, and those assigned to the abstinence-based incentive condition also earned chances to win prizes for submitting substance-free urine samples; the chances of winning prizes increased with continuous time abstinent. Main Outcome Measures: Retention, counseling attendance, total number of substance-free samples provided, percentage of stimulant- and alcohol-free samples submitted, and longest duration of confirmed stimulant abstinence. Results: Participants assigned to the abstinence-based incentive condition remained in treatment for a mean +/- SD of 8.0 +/- 4.2 weeks and attended a mean +/- SD of 19.2.+/- 16.8 counseling sessions compared with 6.9 +/- 4.4 weeks and 15.7 +/- 14.4 sessions for those assigned to the usual care condition (P <.02 for all). Participants in the abstinence-based incentive condition also submitted significantly more stimulant- and alcohol-free samples (P <.001). The abstinence-based incentive group was significantly more likely to achieve 4, 8, and 12 weeks of continuous abstinence than the control group, with odds ratios of 2.5, 2.7, and 4.5, respectively. However, the percentage of positive samples submitted was low overall and did not differ between conditions. Conclusion: The abstinence-based incentive procedure, which provided a mean of $203 in prizes per participant, was efficacious in improving retention and associated abstinence outcomes. C1 Univ Connecticut, Ctr Hlth, Dept Psychiat, Sch Med, Farmington, CT 06030 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Biopharmaceut Res Consultants Inc, Ann Arbor, MI USA. Washington State Univ, Tacoma, WA USA. Univ Calif Los Angeles, Los Angeles, CA USA. Med Univ S Carolina, Charleston, SC 29425 USA. Univ Penn, Philadelphia, PA USA. Treatment Res Inst, Philadelphia, PA USA. Yale Univ, New Haven, CT USA. Univ Colorado, Denver, CO 80202 USA. Natl Inst Drug Abuse, Intramural Res Program, Baltimore, MD USA. RP Petry, NM (reprint author), Univ Connecticut, Ctr Hlth, Dept Psychiat, Sch Med, 263 Farmington Ave, Farmington, CT 06030 USA. EM petry@psychiatry.uchc.edu RI Peirce, Jessica/E-7790-2013; OI Peirce, Jessica/0000-0002-1192-3965; Kirby, Kimberly/0000-0001-6745-3854 FU NIDA NIH HHS [U10DA13034] NR 45 TC 199 Z9 201 U1 4 U2 11 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD OCT PY 2005 VL 62 IS 10 BP 1148 EP 1156 DI 10.1001/archpsyc.62.10.1148 PG 9 WC Psychiatry SC Psychiatry GA 972CD UT WOS:000232430600010 PM 16203960 ER PT J AU Rapkiewicz, AV Hawk, A Noe, A Berman, DM AF Rapkiewicz, AV Hawk, A Noe, A Berman, DM TI Surgical pathology in the era of the civil war - The remarkable life and accomplishments of Joseph Janvier Woodward, MD SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Biographical-Item AB Joseph Janvier Woodward was an assistant surgeon in the US Army during the Civil War, coauthored the definitive works on the mortality and morbidity of that war, attended at the autopsy of President Lincoln, and attended President Garfield after he was shot. He revolutionized the field of photomicroscopy and was one of the first pathologists to use aniline dyes as tissue stains. Yet despite the occasional biographical sketch every few decades, he is largely unknown today. Herein, we review his contributions to surgical pathology and medicine and present modern-day photomicrographs of 140-year-old slides from Woodward's original collection. C1 Natl Canc Inst, Pathol Lab, Bethesda, MD 20892 USA. Armed Forces Inst Pathol, Natl Museum Hlth & Med, Washington, DC 20306 USA. RP Berman, DM (reprint author), Natl Canc Inst, Pathol Lab, Bldg 10,Room 2N212,10 Ctr Dr, Bethesda, MD 20892 USA. EM bermand@mail.nih.gov NR 0 TC 3 Z9 3 U1 0 U2 3 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 2005 VL 129 IS 10 BP 1313 EP 1316 PG 4 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 970RU UT WOS:000232328100018 PM 16196522 ER PT J AU Smolen, JS Aletaha, D Keystone, E AF Smolen, JS Aletaha, D Keystone, E TI Superior efficacy of combination therapy for rheumatoid arthritis - Fact or fiction ? SO ARTHRITIS AND RHEUMATISM LA English DT Review ID PLACEBO-CONTROLLED TRIAL; RANDOMIZED CONTROLLED-TRIAL; ALPHA MONOCLONAL-ANTIBODY; WEEK CLINICAL-TRIAL; DOUBLE-BLIND; ANTIRHEUMATIC THERAPY; SINGLE COMPONENTS; 3 MEDICATIONS; METHOTREXATE; SULFASALAZINE C1 Univ Toronto, MacDonald Ctr Arthritis & Autimmun, Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. Med Univ Vienna, Vienna, Austria. Lainz Hosp, A-1130 Vienna, Austria. NIAMSD, NIH, Bethesda, MD 20892 USA. RP Keystone, E (reprint author), Univ Toronto, MacDonald Ctr Arthritis & Autimmun, Mt Sinai Hosp, 60 Murray St,Room 2-006, Toronto, ON M5G 1X5, Canada. EM edkeystone@mtsinai.on.ca NR 55 TC 49 Z9 53 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD OCT PY 2005 VL 52 IS 10 BP 2975 EP 2983 DI 10.1002/art.21293 PG 9 WC Rheumatology SC Rheumatology GA 973UT UT WOS:000232548800004 PM 16200577 ER PT J AU Dupuis, J Larson, MG Vasan, RS Massaro, JM Wilson, PWF Lipinska, L Corey, D Vita, JA Keaney, JF Benjamin, EJ AF Dupuis, J Larson, MG Vasan, RS Massaro, JM Wilson, PWF Lipinska, L Corey, D Vita, JA Keaney, JF Benjamin, EJ TI Genome scan of systemic biomarkers of vascular inflammation in the Framingham Heart Study: Evidence for susceptibility loci on 1q SO ATHEROSCLEROSIS LA English DT Article DE inflammation; genetics; epidemiology; risk factors; cardiovascular diseases ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; C-REACTIVE PROTEIN; CORONARY-ARTERY-DISEASE; QUANTITATIVE-TRAIT LOCI; E-DEFICIENT MICE; P-SELECTIN GENE; MYOCARDIAL-INFARCTION; CARDIOVASCULAR-DISEASE; LINKAGE ANALYSIS; PLASMA-LEVELS AB Vascular inflammation plays a central role in atherosclerosis and inflammatory biomarkers predict risk of cardiovascular disease (CVD). Thus, finding genes that influence systemic levels of inflammatory biomarkers may provide insights into genetic determinants of vascular inflammation and CVD. We conducted variance-component linkage analyses of blood levels of four biomarkers of vascular inflammation [C-reactive protein (CRP), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), soluble intercellular adhesion molecule-1 (sICAM-1)] in 304 extended families from the Framingham Heart Study, using data from a 10 cM genome scan. We computed p-values by a permutation approach. Heritability estimates ranged from 14% (IL-6) to 44% (MCP-1) after log transforming and adjusting for covariates. Significant linkage to MCP-1 was found on chromosome 1 (LOD = 4.27 at 186 cM; genome-wide p = 0.005), in a region containing inflammatory candidate genes such as SELE, SELP (E- and P-selectin) and CRP. Other linkage peaks with LOD scores >2 were found for MCP-1 on chromosome 1 (LOD = 2.04 at 16 cM; LOD = 2.34 at 70 cM) and chromosome 17 (LOD = 2.44 at 22 cM) and for sICAM-1 on chromosome 1 at 229 cM (LOD = 2.09) less than 5 cM from the interleukin-10 (IL10) gene. Multiple genes on chromosome 1 may influence inflammatory biomarker levels and may have a potential role in development of CVD. (c) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. NHLBI, Framingham Heart Study, Framingham, MA USA. Boston Univ, Sch Med, Dept Prevent Med, Boston, MA 02118 USA. Whitaker Cardiovasc Inst, Evans Mem Dept Med, Boston, MA USA. RP Dupuis, J (reprint author), Boston Univ, Sch Publ Hlth, Dept Biostat, 715 Albany St, Boston, MA 02118 USA. EM dupuis@bu.edu OI Vita, Joseph/0000-0001-5607-1797; Massaro, Joseph/0000-0002-2682-4812; Larson, Martin/0000-0002-9631-1254; Ramachandran, Vasan/0000-0001-7357-5970; Dupuis, Josee/0000-0003-2871-3603; Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [N01-HV-28178, HL04334, HL60886, HL64753, HL70139, HL76784-01, N01-HC-25195]; NIDDK NIH HHS [DK55656] NR 49 TC 64 Z9 64 U1 0 U2 2 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 2005 VL 182 IS 2 BP 307 EP 314 DI 10.1016/j.atherosclerosis.2005.02.015 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 976TM UT WOS:000232756300013 PM 16159603 ER PT J AU Hoffmann, KM Furukawa, M Jensen, RT AF Hoffmann, KM Furukawa, M Jensen, RT TI Duodenal neuroendocrine tumors: Classification, functional syndromes, diagnosis and medical treatment SO BEST PRACTICE & RESEARCH IN CLINICAL GASTROENTEROLOGY LA English DT Review DE duodenal carcinoid; carcinoid; gastrinoma; Zollinger-Ellison syndrome; somatostatinoma; MEN I; gangliocytic paraganglioma; von Recklinghausen's disease ID ZOLLINGER-ELLISON-SYNDROME; MULTIPLE ENDOCRINE NEOPLASIA; SOMATOSTATIN RECEPTOR SCINTIGRAPHY; MALIGNANT CARCINOID-SYNDROME; ISLET CELL TUMORS; SURGICAL-MANAGEMENT; HORMONE CONTENT; LONG-TERM; CLINICAL CHARACTERISTICS; STATISTICAL EVALUATION AB Duodenal neuroendocrine tumors (NETs) comprise 2-3% of all GI endocrine tumors and are increasing in frequency. These include gastrinomas, somatostatinomas, nonfunctional NETs, gangliocytic paragangliomas, and poorly differentiated NE carcinomas. Although, the majority are nonfunctional, these tumors are a frequent cause of Zollinger-Ellison syndrome and can cause other clinical hormonal syndromes (carcinoid, Cushing's, etc.). In this chapter, their epidemiology, clinical aspects, localization, diagnosis and medical treatment are reviewed including the latest advances in each area. C1 NIDDKD, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. RP Jensen, RT (reprint author), NIDDKD, Digest Dis Branch, NIH, Bldg 10,Rm 9C-103,10 Ctr Dr,MSC 1804, Bethesda, MD 20892 USA. EM robertj@bdg10.niddk.nih.gov NR 115 TC 53 Z9 56 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1521-6918 EI 1532-1916 J9 BEST PRACT RES CL GA JI Best Pract. Res. Clin. Gastroenterol. PD OCT PY 2005 VL 19 IS 5 BP 675 EP 697 DI 10.1016/j.bpg.2005.05.009 PG 23 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 989HW UT WOS:000233664500002 PM 16253893 ER PT J AU Pavletic, SZ Illei, GG AF Pavletic, SZ Illei, GG TI The role of immune ablation and stem cell transplantation in severe SLE SO BEST PRACTICE & RESEARCH IN CLINICAL RHEUMATOLOGY LA English DT Article DE biologic therapy; bone marrow transplantation; clinical study; treatment resistant ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; BONE-MARROW-TRANSPLANTATION; HIGH-DOSE CYCLOPHOSPHAMIDE; SEVERE RHEUMATOID-ARTHRITIS; PERIPHERAL-BLOOD STEM; TERM-FOLLOW-UP; AUTOIMMUNE-DISEASE; IMMUNOSUPPRESSIVE THERAPY; INTRAVENOUS CYCLOPHOSPHAMIDE; ACCELERATED ATHEROSCLEROSIS AB High-dose immunosuppression followed by autologous hematopoietic stem cell therapy (HSCT) has the promise of long-term response after a short, intense period of immunosuppressive therapy but it is associated with an increased risk of serious short-term complications. HSCT induces major clinical responses in about 65% of patients with SLE who failed standard therapies. In some of these patients such responses are durable for at least several years, but the curative potential of this procedure in severe SLE is still unknown. Procedure-related mortality varies among studies between 5 and 12% and seems to be lower in relatively larger single center studies. Until more reliable estimates of the actual risks and long-term outcomes become available, patients with potentially life-threatening or disabling major organ involvement who are in acceptable general medical condition should be considered for autologous HSCT if they have failed a reasonable course of standard immunosuppressive therapy. To accomplish the best therapeutic and scientific results, it is necessary to treat all patients in carefully planned protocols by specialized teams of lupus specialists and transplanters. All immunoablative protocols should incorporate carefully planned studies of immune reconstitution to understand the mechanisms of cure or failure. C1 NCI, Expt Transplantat & Autoimmun Branch, Bethesda, MD 20892 USA. NIDCR, Gene Therapy & Therapeut Branch, Bethesda, MD USA. RP Illei, GG (reprint author), NCI, Expt Transplantat & Autoimmun Branch, Bethesda, MD 20892 USA. EM illeig@mail.nih.gov NR 76 TC 10 Z9 13 U1 0 U2 0 PU BAILLIERE TINDALL PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1521-6942 J9 BEST PRACT RES CL RH JI Best Pract. Res. Clin. Rheumatol. PD OCT PY 2005 VL 19 IS 5 BP 839 EP 858 DI 10.1016/j.berh.2005.05.002 PG 20 WC Rheumatology SC Rheumatology GA 968XS UT WOS:000232197100010 PM 16150406 ER PT J AU Alves, G Yu, YK AF Alves, G Yu, YK TI Robust accurate identification of peptides (RAId): deciphering MS2 data using a structured library search with de novo based statistics SO BIOINFORMATICS LA English DT Article ID TANDEM MASS-SPECTROMETRY; ELECTROSPRAY IONIZATION; PROTEIN IDENTIFICATION; SEQUENCE DATABASES; MS/MS; PROTEOMES; MODEL AB Motivation: The key to MS -based proteomics is peptide sequencing. The major challenge in peptide sequencing, whether library search or de novo, is to better infer statistical significance and better attain noise reduction. Since the noise in a spectrum depends on experimental conditions, the instrument used and many other factors, it cannot be predicted even if the peptide sequence is known. The characteristics of the noise can only be uncovered once a spectrum is given. We wish to overcome such issues. Results: We designed RAId to identify peptides from their associated tandem mass spectrometry data. RAId performs a novel de novo sequencing followed by a search in a peptide library that we created. Through de novo sequencing, we establish the spectrum-specific background score statistics for the library search. When the database search fails to return significant hits, the top-ranking de novo sequences become potential candidates for new peptides that are not yet in the database. The use of spectrum-specific background statistics seems to enable RAId to perform well even when the spectral quality is marginal. Other important features of RAId include its potential in de novo sequencing alone and the ease of incorporating post-translational modifications. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Yu, YK (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM yyu@ncbi.nlm.nih.gov FU Intramural NIH HHS NR 32 TC 15 Z9 15 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD OCT 1 PY 2005 VL 21 IS 19 BP 3726 EP 3732 DI 10.1093/bioinformatics/bti620 PG 7 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 974MO UT WOS:000232596100005 PM 16105903 ER PT J AU Kojima, C Sakurai, T Waalkes, MP Himeno, S AF Kojima, C Sakurai, T Waalkes, MP Himeno, S TI Cytolethality of glutathione conjugates with monomethylarsenic or dimethylarsenic compounds SO BIOLOGICAL & PHARMACEUTICAL BULLETIN LA English DT Article DE arsenic; glutathione (GSH); dimethylarsinic; monomethylarsonic; GSH conjugate ID ORGANIC ARSENIC COMPOUNDS; URINARY-EXCRETION; INDUCED APOPTOSIS; DIFFERENT ROLES; TRIOXIDE AS2O3; ACID; CELLS; MACROPHAGES; MECHANISMS; INDUCTION AB Arsenicals are known to be toxic and carcinogenic in humans. Inorganic arsenicals are enzymatically methylated to monomethylarsonic acid (MMAsv) and dimethylarsinic acid (DMAsv), which are the major pentavalent methyl arsenic metabolites. Recent reports indicate that trivalent methyl arsenicals are produced through methylation of inorganic arsenicals and participate in arsenic poisoning. Trivalent methyl arsenicals may be generated as arsenical-glutathione conjugates, such as monomethylarsonous diglutathione (MMAs'"DG) and dimethylarsinous glutathione (DMAs"'G), during the methylation process. It has been well known that reduced glutathione (GSH) reduces MMAsv and DMAsv in vitro, and produces MMAs"'DG and DMAs'"G. Some studies have shown that exogenous GSH increased cytolethality of MMAsv and DMAsv in vitro, while other studies have suggested that exogenous GSH decreased them. In this study, we examined the true effects of exogenous GSH on the cytolethality of MMAsv and DMAsv by investigating reactions between various concentrations of MMAsv or DMAsv and GSH. GSH significantly increased the cytolethality and cellular uptake of pentavalent methyl arsenicals when GSH over 25 mm was pre-incubated with mm levels of arsenicals, and this cytolethality might have been caused by arsenical-GSH conjugate generation. However, GSH at less than 25 mm did not affect the cytolethality and cellular uptake of pentavalent methyl arsenicals. These findings suggest that high concentrations of arsenicals and GSH are needed to form arsenical-GSH conjugates and to show significant cytolethality. Furthermore, we speculated that MMAs"'DG and DMAs"'G may separate into trivalent methyl arsenicals and glutathione, which are then transported into cells where they show significant cytolethality. C1 Tokushima Bunri Univ, Fac Pharmaceut Sci, Lab Mol Nutr & Toxicol, Tokushima 7708514, Japan. NIEHS, NCI, Comparat Carcinogenesis Lab, Inorgan Carcinogenesis Sect,NIH, Res Triangle Pk, NC 27709 USA. RP Sakurai, T (reprint author), Tokushima Bunri Univ, Fac Pharmaceut Sci, Lab Mol Nutr & Toxicol, Yamashiro Cho, Tokushima 7708514, Japan. EM teruaki@ph.bunri-u.ac.jp NR 37 TC 9 Z9 12 U1 0 U2 4 PU PHARMACEUTICAL SOC JAPAN PI TOKYO PA 2-12-15 SHIBUYA, SHIBUYA-KU, TOKYO, 150-0002, JAPAN SN 0918-6158 J9 BIOL PHARM BULL JI Biol. Pharm. Bull. PD OCT PY 2005 VL 28 IS 10 BP 1827 EP 1832 DI 10.1248/bpb.28.1827 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 975RY UT WOS:000232680800003 PM 16204930 ER PT J AU Biederman, J James, RS AF Biederman, J James, RS TI Advances in the neurobiology of pediatric bipolar disorder SO BIOLOGICAL PSYCHIATRY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Res, Yawkey Ctr Outpatient Care, Boston, MA 02114 USA. NIMH, Pediat Mood Regulat & Biopolar Program, Bethesda, MD USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Res, Yawkey Ctr Outpatient Care, YAW-6A-6900,32 Fruit St, Boston, MA 02114 USA. EM bieclerman@helix.mgh.harvard.edu NR 12 TC 2 Z9 2 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD OCT 1 PY 2005 VL 58 IS 7 BP 515 EP 516 DI 10.1016/j.biopsych.2005.09.002 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 978IH UT WOS:000232866300001 PM 16239159 ER PT J AU Dickstein, DP Garvey, M Pradella, AG Greenstein, DK Sharp, WS Castellanos, FX Pine, DS Leibenluft, E AF Dickstein, DP Garvey, M Pradella, AG Greenstein, DK Sharp, WS Castellanos, FX Pine, DS Leibenluft, E TI Neurologic examination abnormalities in children with bipolar disorder or Attention-deficit/hyperactivity disorder SO BIOLOGICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Conference on Pediatric Bipolar Disorder CY APR 02-03, 2004 CL Boston, MA DE bipolar disorder; attention-deficit/hyperactivity disorder; neurologic examination; child; adolescent ID DEFICIT HYPERACTIVITY DISORDER; SOFT SIGNS; RESPONSE-INHIBITION; PSYCHIATRIC-DISORDER; 6-YEAR-OLD CHILDREN; TEST-PERFORMANCE; JUVENILE MANIA; MOTOR; ADHD; ADOLESCENTS AB Background: Atteiition-deficit/hyperactivity disorder (ADHD) and bipolar disorder (BPD) are frequently comorbid and overlapping diagnoses. To move beyond diagnosis toward unique pathophysiology, we evaluated both ADHD and BPD children for neurologic examination abnormalities (NEAs) in comparison with normal control (NC) children. Methods: We performed the Revised Physical and Neurological Examination for Soft Signs in three groups (ADHD, BPD, NC). Then, a rater blind to diagnosis evaluated their motor performance. Results were analyzed with a multiple analysis of covariance. Results. Subjects with ADHD were impaired on repetitive task reaction time. In contrast, pediatric BPD subjects, both with and without comorbid ADHD. were impaired on sequential task reaction time. Conclusions: This differential pattern of NEAs by diagnosis suggests pathophysiologic differences between ADHD and BPD in children, Repetitive motor performance requires inhibition of nonrelevant movements; ADHD subjects' impairment in this domain supports the hypothesis that ADHD involves a core deficit of fronto-striato- basal ganglia neurocircuitry. In contrast, BPD subjects' impaired sequential motor performance is consistent with behavioral data showing impaired attentional set-shifting and reversal learning in BPD subjects. Further study going beyond symptom description to determine pathophysiologic differences, is required to refine neuronal models of these often comorbid diagnoses. C1 NIMH, Pediat & Dev Neuropsychiat Branch, Bethesda, MD 20892 USA. NYU, Ctr Child Study, New York, NY USA. RP Dickstein, DP (reprint author), NIMH, Pediat & Dev Neuropsychiat Branch, 10 Ctr Dr MSC 1255,Bldg 10-Room 4N208, Bethesda, MD 20892 USA. EM Dicksted@intra.nimh.nih.gov RI Dickstein, Daniel/L-3210-2016; OI Dickstein, Daniel/0000-0003-1647-5329; Castellanos, Francisco/0000-0001-9192-9437 FU Intramural NIH HHS; NIMH NIH HHS [5 U13 MH64077-03] NR 65 TC 43 Z9 45 U1 3 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 2005 VL 58 IS 7 BP 517 EP 524 DI 10.1016/j.biopsych.2004.12.010 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 978IH UT WOS:000232866300002 PM 16239160 ER PT J AU Rich, BA Schmajuk, M Perez-Edgar, KE Pine, DS Fox, NA Leibenluft, E AF Rich, BA Schmajuk, M Perez-Edgar, KE Pine, DS Fox, NA Leibenluft, E TI The impact of reward, punishment, and frustration on attention in pediatric bipolar disorder SO BIOLOGICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Conference on Pediatric Bipolar Disorder CY APR 02-03, 2004 CL Boston, MA DE bipolar disorder; children; attention; emotion; frustration; ERPs ID DEFICIT HYPERACTIVITY DISORDER; EVENT-RELATED POTENTIALS; VISUAL-ATTENTION; DECISION-MAKING; SELF-REGULATION; RATING-SCALE; CONTROL BOYS; CHILDREN; MANIA; RELIABILITY AB Background: Theories in afftective neuroscience suggest that mood disorders involve perturbations in attention-emotion interactions. We tested the hypothesis that frustration adversely impacts attention and behavior in children with bipolar disorder (BPD). Methods: Thirty-five children with BPD and 26 normal control subjects completed: 1) a Posner attention task with feedback but no contingencies; 2) an affective Posner with contingencies; and 3) an affective Posner that used rigged feedback to induce frustration. Reaction time (RT) and event-related potential (ERP) data were collected. Results:At baseline (task 1), there were no between-group differences in behavior or ERPs. Children with BPD exhibited reduced parietal P3 amplitude on task 3 only. On trials occurring after negative feedback, control subjects showed decreased RT when contingencies were introduced (task 2), whereas BPD subjects did not. Conclusions: The introduction of contingencies was associated with impaired performance of children with BPD, suggesting deficits in their ability to adapt to changing contingencies. In addition, frustration was associated with disrupted attention allocation in children with BPD. We hypothesize that children with BPD inappropriately deployed attention to their internal/frustration rather than to the task, causing impaired performance. C1 NIMH, Pediat & Dev Neuropsychiat Branch, Bethesda, MD 20892 USA. NIMH, Sect Dev & Affect Neurosci, Mood & Anxiety Program, Dept Hlth & Human Serv,NIH, Bethesda, MD USA. Univ Maryland, Child Dev Lab, College Pk, MD USA. RP Rich, BA (reprint author), NIMH, Pediat & Dev Neuropsychiat Branch, 10 Ctr Dr,MSC 1255,Bldg 10,Room 4N208, Bethesda, MD 20892 USA. EM brendanrich@mail.nih.gov RI Perez-Edgar, Koraly/B-8463-2008; OI Perez-Edgar, Koraly/0000-0003-4051-9563 FU NIMH NIH HHS [5 U13 MH64077-03] NR 55 TC 50 Z9 52 U1 4 U2 10 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 2005 VL 58 IS 7 BP 532 EP 539 DI 10.1016/j.biopsych.2005-01.006 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 978IH UT WOS:000232866300004 PM 15953589 ER PT J AU Sokolic, RA Bauer, TR Gu, YC Hai, M Tuschong, LM Burkholder, T Colenda, L Bacher, J Starost, MF Hickstein, DD AF Sokolic, RA Bauer, TR Gu, YC Hai, M Tuschong, LM Burkholder, T Colenda, L Bacher, J Starost, MF Hickstein, DD TI Nonmyeloablative conditioning with busulfan before matched littermate bone marrow transplantation results in reversal of the disease phenotype in canine leukocyte adhesion deficiency SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE canine leukocyte adhesion deficiency; nonmyeloablative conditioning; busulfan; bone; marrow transplantation ID STEM-CELL TRANSPLANTATION; VERSUS-HOST DISEASE; CHRONIC MYELOGENOUS LEUKEMIA; TOTAL-BODY IRRADIATION; MIXED CHIMERISM; HEMATOPOIETIC STEM; INTRAVENOUS BUSULFAN; ALLOGENEIC TRANSPLANTATION; HEMATOLOGIC MALIGNANCIES; P150,95 GLYCOPROTEINS AB Leukocyte adhesion deficiency (LAD)-1, a primary immunodeficiency disease caused by molecular defects in the leukocyte integrin CD18 molecule, is characterized by recurrent, life-threatening bacterial infections. Myeloablative hematopoietic stem cell transplantation is the only curative treatment for LAD-1. Recently, canine LAD (CLAD) has been shown to be a valuable animal model for the preclinical testing of nonmyeloablative transplantation regimens for the treatment of children with LAD-1. To develop new allogeneic transplantation approaches for LAD-1, we assessed a nonmyeloablative conditioning regimen consisting of busulfan as a single agent before matched littermate allogeneic bone marrow, transplantation in CLAD. Three CLAD dogs received busulfan 10 mg/kg intravenously before infusion of matched littermate bone marrow, and all dogs received posttransplantation immunosuppression with cyclosporin A and mycophenolate mofetil. Initially, all 3 dogs became mixed chimeras, and levels of donor chimerism sufficient to reverse the CLAD phenotype persisted in 2 animals. The third dog maintained donor microchimerism with an attenuated CLAD phenotype. These 3 dogs have all been followed up for at least I year after transplantation. These results indicate that a nomnyeloablative conditioning regimen with chemotherapy alone is capable of generating stable mixed chimerism and reversal of the disease phenotype in CLAD. (c) 2005 American Society for Blood and Marrow Transplaltation. C1 NCI, Expt Transplantat & Immunol Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. NIH, Div Vet Resources, Off Res Serv, Bethesda, MD 20892 USA. RP Sokolic, RA (reprint author), NCI, Expt Transplantat & Immunol Branch, Canc Res Ctr, NIH, Bldg 10 CRC,Room 3-3264,MSC 1203,10 Ctr Dr, Bethesda, MD 20892 USA. EM sokolicr@mail.nih.gov RI Sokolic, Robert/I-6072-2012 FU Intramural NIH HHS; NCI NIH HHS [Z01 SC010384-05] NR 38 TC 17 Z9 18 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD OCT PY 2005 VL 11 IS 10 BP 755 EP 763 DI 10.1016/j.bbmt.2005.07.011 PG 9 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 976KH UT WOS:000232731800002 PM 16182176 ER PT J AU Jefferson, WN Padilla-Banks, E Newbold, RR AF Jefferson, WN Padilla-Banks, E Newbold, RR TI Adverse effects on female development and reproduction in CD-1 mice following neonatal exposure to the phytoestrogen genistein at environmentally relevant doses SO BIOLOGY OF REPRODUCTION LA English DT Article DE developmental biology; female reproductive tract; mechanisms of hormone action; ovary ID ESTROGEN-RECEPTOR-BETA; SPRAGUE-DAWLEY RATS; SOY-BASED FORMULA; UDP-GLUCURONOSYLTRANSFERASE; UTERINE ADENOCARCINOMA; MAMMARY TUMORIGENESIS; POSTNATAL-DEVELOPMENT; ISOFLAVONE CONTENT; HUMAN-LIVER; DIETHYLSTILBESTROL AB Outbred female CD-1 mice were treated with genistein (Gen), the primary phytoestrogen in soy, by s.c. injections on Neonatal Days 1-5 at doses of 0.5, 5, or 50 mg/kg per day (Gen-0.5, Gen-5, and Gen-50). The day of vaginal opening was observed in mice treated with Gen and compared with controls, and although there were some differences, they were not statistically significant. Gen-treated mice had prolonged estrous cycles with a dose- and age-related increase in severity of abnormal cycles. Females treated with Gen-0.5 or Gen-5 bred to control males at 2, 4, and 6 mo showed statistically significant decreases in the number of live pups over time with increasing dose; at 6 mo, 60% of the females in the Gen-0.5 group and 40% in the Gen-5 group delivered live pups compared with 100% of controls. Mice treated with Gen-50 did not deliver live pups. At 2 mo, > 60% of the mice treated with Gen-50 were fertile as determined by uterine implantation sites, but pregnancy was not maintained; pregnancy loss was characterized by fewer, smaller implantation sites and increased reabsorptions. Mice treated with lower doses, of Gen had increased numbers of corpora lutea compared with controls, while mice treated with the highest dose had decreased numbers; however, superovulation with eCG/hCG yielded similar numbers of oocytes as controls. Serum levels of progesterone, estradiol, and testosterone were similar between Gen-treated and control mice when measured before puberty and during pregnancy. In summary, neonatal treatment with Gen caused abnormal estrous cycles, altered ovarian function, early reproductive senescence, and subfertility/infertility at environmentally relevant doses. C1 NIEHS, Dev Endocrinol Sect, Res Triangle Pk, NC 27709 USA. NIEHS, Mol Toxicol Lab, Res Triangle Pk, NC 27709 USA. N Carolina State Univ, Dept Environm & Mol Toxicol, Raleigh, NC 27605 USA. RP Jefferson, WN (reprint author), NIEHS, Dev Endocrinol Sect, POB 12233,Mail Drop E4-02,111 Alexander Dr,South, Res Triangle Pk, NC 27709 USA. EM jeffers1@niehs.nih.gov NR 60 TC 91 Z9 97 U1 6 U2 18 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 2005 VL 73 IS 4 BP 798 EP 806 DI 10.1095/biolreprod.105.041277 PG 9 WC Reproductive Biology SC Reproductive Biology GA 967EB UT WOS:000232073200027 PM 15930323 ER PT J AU Paik, S AF Paik, S TI Development and validation of multi-gene prognostic assay for ER plus breast cancer SO BIOMEDICINE & PHARMACOTHERAPY LA English DT Meeting Abstract CT 1st Annual Conference of the Organization-for-Oncology-and-Transitional-Research CY OCT 15-16, 2004 CL Hong Kong, PEOPLES R CHINA SP Org Oncol Transition Res C1 NSABP, Div Pathol, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0753-3322 J9 BIOMED PHARMACOTHER JI Biomed. Pharmacother. PD OCT PY 2005 VL 59 SU 2 BP S394 EP S394 DI 10.1016/S0753-3322(05)80089-7 PG 1 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 999XD UT WOS:000234423600050 ER PT J AU Paik, S AF Paik, S TI Neoadjuvant trials for discovery and validation of predictive markets - a new NSABP clinical trial paradigm SO BIOMEDICINE & PHARMACOTHERAPY LA English DT Meeting Abstract CT 1st Annual Conference of the Organization-for-Oncology-and-Transitional-Research CY OCT 15-16, 2004 CL Hong Kong, PEOPLES R CHINA SP Org Oncol Transition Res C1 NSABP, Div Pathol, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0753-3322 J9 BIOMED PHARMACOTHER JI Biomed. Pharmacother. PD OCT PY 2005 VL 59 SU 2 BP S325 EP S325 DI 10.1016/S0753-3322(05)80064-2 PG 1 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 999XD UT WOS:000234423600025 ER PT J AU Salganik, MP Milford, EL Hardie, DL Shaw, S Wand, MP AF Salganik, MP Milford, EL Hardie, DL Shaw, S Wand, MP TI Classifying antibodies using flow cytometry data: Class prediction and class discovery SO BIOMETRICAL JOURNAL LA English DT Article DE classification; monoclonal antibodies; flow cytometry; dissimilarity measure; kernel smoothing; SiZer; class discovery; class prediction; unsupervised learning; supervised learning AB Classifying monoclonal antibodies, based on the similarity of their binding to the proteins (antigens) on the surface of blood cells, is essential for progress in immunology, hematology and clinical medicine. The collaborative efforts of researchers from many countries have led to the classification of thousands of antibodies into 247 clusters of differentiation (CD). Classification is based on flow cytometry and biochemical data. In preliminary classifications of antibodies based on flow cytometry data, the object requiring classification (an antibody) is described by a set of random samples from unknown densities of fluorescence intensity. An individual sample is collected in the experiment, where a population of cells of a certain type is stained by the identical fluorescently marked replicates of the antibody of interest. Samples are collected for multiple cell types. The classification problems of interest include identifying new CDs (class discovery or unsupervised learning) and assigning new antibodies to the known CD clusters (class prediction or supervised learning). These problems have attracted limited attention from statisticians. We recommend a novel approach to the classification process in which a computer algorithm suggests to the analyst the subset of the "most appropriate" classifications of an antibody in class prediction problems or the "most similar" pairs/groups of antibodies in class discovery problems. The suggested algorithm speeds up the analysis of a flow cytometry data by a factor 10-20. This allows the analyst to focus on the interpretation of the automatically suggested preliminary classification solutions and on planning the subsequent biochemical experiments. C1 Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. Univ Birmingham, Biomed Res Inst, MRC, Ctr Immune Regulat, Birmingham 2TT, W Midlands, England. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. Univ New S Wales, Sch Math, Dept Stat, Sydney, NSW 2052, Australia. RP Salganik, MP (reprint author), Harvard Univ, Sch Publ Hlth, Dept Biostat, 665 Huntington Ave, Boston, MA 02115 USA. EM salganik@hsph.harvard.edu RI Wand, Matt /F-9413-2012 OI Wand, Matt /0000-0003-2555-896X NR 31 TC 1 Z9 1 U1 0 U2 1 PU AKADEMIE VERLAG GMBH PI BERLIN PA PALISADENSTR 40, D-10243 BERLIN, GERMANY SN 0323-3847 J9 BIOMETRICAL J JI Biom. J. PD OCT PY 2005 VL 47 IS 5 BP 740 EP 754 DI 10.1002/bimj.200310142 PG 15 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 979BK UT WOS:000232916900013 PM 16385913 ER PT J AU Peter, C Hummer, G AF Peter, C Hummer, G TI Ion transport through membrane-spanning nanopores studied by molecular dynamics simulations and continuum electrostatics calculations SO BIOPHYSICAL JOURNAL LA English DT Article ID FREE-ENERGY CALCULATIONS; NERNST-PLANCK THEORY; BROWNIAN DYNAMICS; POTASSIUM CHANNEL; LIQUID WATER; K+ CHANNEL; MECHANOSENSITIVE CHANNEL; COMPUTER-SIMULATIONS; PROTON TRANSLOCATION; GRAMICIDIN CHANNEL AB Narrow hydrophobic regions are a common feature of biological channels, with possible roles in ion-channel gating. We study the principles that govern ion transport through narrow hydrophobic membrane pores by molecular dynamics simulation of model membranes formed of hexagonally packed carbon nanotubes. We focus on the factors that determine the energetics of ion translocation through such nonpolar nanopores and compare the resulting free-energy barriers for pores with different diameters corresponding to the gating regions in closed and open forms of potassium channels. Our model system also allows us to compare the results from molecular dynamics simulations directly to continuum electrostatics calculations. Both simulations and continuum calculations show that subnanometer wide pores pose a huge free-energy barrier for ions, but a small increase in the pore diameter to similar to 1 nm nearly eliminates that barrier. We also find that in those wider channels the ion mobility is comparable to that in the bulk phase. By calculating local electrostatic potentials, we show that the long range Coulomb interactions of ions are strongly screened in the wide water-filled channels. Whereas continuum calculations capture the overall energetics reasonably well, the local water structure, which is not accounted for in this model, leads to interesting effects such as the preference of hydrated ions to move along the pore wall rather than through the center of the pore. C1 NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. EM gerhard.hummer@nih.gov RI Peter, Christine/E-1513-2011; Hummer, Gerhard/A-2546-2013 OI Hummer, Gerhard/0000-0001-7768-746X NR 87 TC 125 Z9 127 U1 5 U2 45 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD OCT PY 2005 VL 89 IS 4 BP 2222 EP 2234 DI 10.1529/biophysj.105.065946 PG 13 WC Biophysics SC Biophysics GA 968FP UT WOS:000232147600007 PM 16006629 ER PT J AU Scheidt, HA Huster, D Gawrisch, K AF Scheidt, HA Huster, D Gawrisch, K TI Diffusion of cholesterol and its precursors in lipid membranes studied by H-1 pulsed field gradient magic angle spinning NMR SO BIOPHYSICAL JOURNAL LA English DT Article ID ELASTIC NEUTRON-SCATTERING; SOLID-STATE NMR; LATERAL DIFFUSION; MAGNETIC-RESONANCE; ANISOTROPIC MOTION; STEROL STRUCTURE; MAS-NMR; BILAYERS; SPECTROSCOPY; LANOSTEROL AB Cholesterol content is critical for membrane functional properties. We studied the influence of cholesterol and its precursors desmosterol and lanosterol on lateral diffusion of phospholipids and sterols by H-1 pulsed field gradients ( PFG) magic angle spinning ( MAS) NMR spectroscopy. The high resolution of resonances afforded by MAS NMR permitted simultaneous diffusion measurements on 1,2-dipalmitoyl-sn-glycero-3-phosphocholine ( DPPC) and sterols. The cholesterol diffusion mirrored the DPPC behavior,but rates were slightly higher at all cholesterol concentrations. DPPC and cholesterol diffusion rates decreased and became cholesterol concentration dependent with the onset of liquid-ordered phase formation. The activation energies of diffusion in the coexistence region of liquid-ordered/liquid-disordered phases are higher by about a factor of 2 compared to pure DPPC and to the pure liquid-ordered state formed at higher cholesterol concentrations. We assume that the higher activation energies are a reflection of lipid diffusion across domain boundaries. In lanosterol- and desmosterol- containing membranes, the DPPC and sterol diffusion coefficients are somewhat higher. Whereas the desmosterol rates are only slightly higher than those of DPPC, the lanosterol diffusion rates significantly exceed DPPC rates, indicating a weaker interaction between DPPC and lanosterol. C1 NIAAA, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD 20892 USA. Univ Leipzig, Inst Med Phys & Biophys, D-04107 Leipzig, Germany. Univ Leipzig, Jr Res Grp, Biotechnol Biomed Ctr, D-04107 Leipzig, Germany. RP Gawrisch, K (reprint author), NIAAA, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD 20892 USA. EM gawrisch@helix.nih.gov RI Scheidt, Holger A./C-1416-2014 FU Intramural NIH HHS NR 38 TC 91 Z9 94 U1 3 U2 15 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD OCT PY 2005 VL 89 IS 4 BP 2504 EP 2512 DI 10.1529/biophysj.105.062018 PG 9 WC Biophysics SC Biophysics GA 968FP UT WOS:000232147600031 PM 16085761 ER PT J AU Thaler, C Koushik, SV Blank, PS Vogel, SS AF Thaler, C Koushik, SV Blank, PS Vogel, SS TI Quantitative multiphoton spectral imaging and its use for measuring resonance energy transfer SO BIOPHYSICAL JOURNAL LA English DT Article ID PROTEIN-PROTEIN INTERACTIONS; FLUORESCENT PROTEIN; LIVING CELLS; CONFOCAL IMAGES; MICROSCOPY; FRET; DNA; COLOCALIZATION; RESOLUTION; DYNAMICS AB Protein labeling with green fluorescent protein derivatives has become an invaluable tool in cell biology. Protein quantification, however, is difficult when cells express constructs with overlapping fluorescent emissions. Under these conditions, signal separation using emission filters is inherently inefficient. Spectral imaging solves this problem by recording emission spectra directly. Unfortunately, linear unmixing, the algorithm used for quantifying individual fluorophores from emission spectra, fails when resonance energy transfer ( RET) is present. We therefore sought to develop an unmixing algorithm that incorporates RET. An equation for spectral emission incorporating RET was derived and an assay based on this formalism, spectral RET ( sRET), was developed. Standards with defined RET efficiencies and with known Cerulean/ Venus ratios were constructed and used to test sRET. We demonstrate that sRET analysis is a comprehensive, photon- efficient method for imaging RET efficiencies and accurately determines donor and acceptor concentrations in living cells. C1 NIAAA, NIH, Bethesda, MD 20892 USA. NICHHD, NIH, Bethesda, MD 20892 USA. RP Vogel, SS (reprint author), NIAAA, NIH, Bethesda, MD 20892 USA. EM stevevog@mail.nih.gov RI Vogel, Steven/A-3585-2012; OI Vogel, Steven/0000-0002-3005-2667 NR 36 TC 97 Z9 98 U1 3 U2 9 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD OCT PY 2005 VL 89 IS 4 BP 2736 EP 2749 DI 10.1529/biophysj.105.061853 PG 14 WC Biophysics SC Biophysics GA 968FP UT WOS:000232147600056 PM 16040744 ER PT J AU Skupsky, R Losert, W Nossal, RJ AF Skupsky, R Losert, W Nossal, RJ TI Distinguishing modes of eukaryotic gradient sensing SO BIOPHYSICAL JOURNAL LA English DT Article ID CELL-MOVEMENT; LIVING CELLS; IN-VIVO; PHOSPHATIDYLINOSITOL 3,4,5-TRISPHOSPHATE; PHOSPHOINOSITIDE 3-KINASE; CHEMOATTRACTANT RECEPTOR; NEUTROPHIL CHEMOTAXIS; ACTIN CYTOSKELETON; PATTERN-FORMATION; SPATIAL-ANALYSIS AB We develop a mathematical model of phosphoinositide-mediated gradient sensing that can be applied to chemotactic behavior in highly motile eukaryotic cells such as Dictyostelium and neutrophils. We generate four variants of our model by adjusting parameters that control the strengths of coupled positive feedbacks and the importance of molecules that translocate from the cytosol to the membrane. Each variant exhibits a qualitatively different mode of gradient sensing. Simulations of characteristic behaviors suggest that differences between the variants are most evident at transitions between efficient gradient detection and failure. Based on these results, we propose criteria to distinguish between possible modes of gradient sensing in real cells, where many biochemical parameters may be unknown. We also identify constraints on parameters required for efficient gradient detection. Finally, our analysis suggests how a cell might transition between responsiveness and nonresponsiveness, and between different modes of gradient sensing, by adjusting its biochemical parameters. C1 NICHHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. Univ Maryland, Dept Phys, College Pk, MD 20742 USA. RP NICHHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. EM nossalr@mail.nih.gov NR 74 TC 42 Z9 42 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 EI 1542-0086 J9 BIOPHYS J JI Biophys. J. PD OCT PY 2005 VL 89 IS 4 BP 2806 EP 2823 DI 10.1529/biophysj.105.061564 PG 18 WC Biophysics SC Biophysics GA 968FP UT WOS:000232147600062 PM 16085764 ER PT J AU Rawat, SS Johnson, BT Puri, A AF Rawat, SS Johnson, BT Puri, A TI Sphingolipids: Modulators of HIV-1 infection and pathogenesis SO BIOSCIENCE REPORTS LA English DT Article DE viral entry; lipid rafts; cholesterol; sphingolipids; ceramide; membrane fusion ID HUMAN-IMMUNODEFICIENCY-VIRUS; BUTYLDEOXYNOJIRIMYCIN-MEDIATED INHIBITION; BLOOD GROUP PHENOTYPES; V3 LOOP; ENVELOPE GLYCOPROTEIN; CELL-LINES; GLUCOSYLCERAMIDE SYNTHASE; ERYTHROCYTE GLYCOSPHINGOLIPIDS; GALACTOSYL CERAMIDE; GANGLIOSIDE GM3 AB HIV-1 infects host cells by sequential interactions of its fusion protein (gp120-gp41) with receptors CD4, CXCR4 and/or CCR5 followed by fusion of viral and host membranes. Studies indicate that additional factors such as receptor density and composition of viral and cellular lipids can dramatically modulate the fusion reaction. Lipid rafts, which primarily consist of sphingolipids and cholesterol, have been implicated for infectious route of HIV-1 entry. Plasma membrane Glycosphingolipids (GSLs) have been proposed to support HIV-1 infection in multiple ways: (a) as alternate receptor(s) for CD4-independent entry in neuronal and other cell types, (b) viral transmission, and (c) gp120-gp41-mediated membrane fusion. However, the exact mechanism(s) by which GSLs support fusion is still elusive. This article will focus on the contribution of target membrane sphingolipids and their metabolites in modulating viral entry. We will discuss the current working hypotheses underlying the mechanisms by which these lipids promote and/or block HIV-1 entry. Recent approaches in the design and development of novel glycosyl derivatives, as anti-HIV agents will be summarized. C1 NCI, Lab Expt & Computat Biol, Ctr Canc Res, NIH, Frederick, MD 21702 USA. RP Puri, A (reprint author), NCI, Lab Expt & Computat Biol, Ctr Canc Res, NIH, POB B,Bldg 469,Rm 211,Miller Dr, Frederick, MD 21702 USA. EM apuri@helix.nih.gov NR 72 TC 30 Z9 31 U1 0 U2 0 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0144-8463 J9 BIOSCIENCE REP JI Biosci. Rep. PD OCT PY 2005 VL 25 IS 5-6 BP 329 EP 343 DI 10.1007/s10540-005-2894-5 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 987DY UT WOS:000233499800005 PM 16307380 ER PT J AU MacKinnon, DF Potash, JB McMahon, FJ Simpson, SG DePaulo, JR Zandi, PP AF MacKinnon, DF Potash, JB McMahon, FJ Simpson, SG DePaulo, JR Zandi, PP CA Natl Inst Mental Hlth Bipolar Dis TI Rapid mood switching and suicidality in familial bipolar disorder SO BIPOLAR DISORDERS LA English DT Article DE bipolar disorder; family study; impulsivity; panic disorder; rapid cycling; suicide ID PANIC DISORDER; BEHAVIOR; RISK; IMPULSIVITY; MANIA; ASSOCIATION; AGGRESSION; DEPRESSION; GENETICS; SPECTRUM AB Objectives: Rapidly alternating or mixed mood states in bipolar disorder are associated with a particularly high risk for suicidal behavior. Are individuals with these patterns of illness more likely to develop suicidal intentions, or are they less able to resist them? This analysis examines the specific contribution of rapid switching and other variables to the relative likelihood of having or acting on self-reported suicidal thought and action, in a large group of individuals with bipolar disorder. Methods: The analysis included 1574 family members with bipolar disorder interviewed for a multi-site bipolar disorder genetic linkage study. Two models were tested, using the same set of demographic and clinical data points as independent variables. One model tested the influence of rapid switching and other variables on self-reported suicidal thought or action (i.e., suicidality), while the other tested the influences on suicidal action only among those who reported a history of suicidality. Results: Over 75% of subjects had contemplated suicide and 38% reported a history of suicidal behavior. A history of rapid switching was associated with higher likelihood of a history of suicidality, as was panic disorder. Familial suicidal behavior, as well as drug abuse, increased the likelihood of suicidal action among suicidal individuals, but did not increase the likelihood of becoming suicidal. Female sex, early age at onset, and several demographic factors were associated with both facets of suicidality. Conclusion: Factors associated with high acuity of distress, such as panic attacks and unstable moods, appear to enhance the risk of suicidality in general. Factors that affected the threshold for action without increasing suicidality overall can also be seen as markers of impulsive decision-making. Of the two distinct kinds of suicidal risk, the latter - the likelihood of action given intent - appears to be the more familial. C1 Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. NIMH, Genet Basis Mood & Anxiety Disorders, US Dept HHS, NIH, Bethesda, MD 20892 USA. Univ Colorado, Hlth Sci Ctr, Dept Psychiat, Denver, CO 80262 USA. Indiana Univ, Bloomington, IN 47405 USA. Rush Univ, Chicago, IL 60612 USA. Univ Iowa, Iowa City, IA 52242 USA. Univ Penn, Philadelphia, PA 19104 USA. Univ Calif Irvine, Irvine, CA USA. Univ Calif San Diego, San Diego, CA 92103 USA. Univ Chicago, Chicago, IL 60637 USA. Washington Univ, St Louis, MO USA. Johns Hopkins Univ, Sch Med, Bloomberg Sch Publ Hlth, Baltimore, MD USA. RP MacKinnon, DF (reprint author), Meyer 3-181,600 N Wolfe St, Baltimore, MD 21287 USA. EM dmackin@jhmi.edu RI McMahon, Francis/A-7290-2009; OI Nurnberger, John/0000-0002-7674-1767; McMahon, Francis/0000-0002-9469-305X NR 46 TC 36 Z9 38 U1 1 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1398-5647 J9 BIPOLAR DISORD JI Bipolar Disord. PD OCT PY 2005 VL 7 IS 5 BP 441 EP 448 DI 10.1111/j.1399-5618.2005.00236.x PG 8 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 965WD UT WOS:000231980700006 PM 16176437 ER PT J AU Chen, X Murakami, T Oppenheim, JJ Howard, OMZ AF Chen, X Murakami, T Oppenheim, JJ Howard, OMZ TI Triptolide, a constituent of immunosuppressive Chinese herbal medicine, is a potent suppressor of dendritic-cell maturation and trafficking SO BLOOD LA English DT Article ID WILFORDII HOOK-F; CHEMOKINE RECEPTOR EXPRESSION; TRIPTERYGIUM-WILFORDII; T-LYMPHOCYTE; RHEUMATOID-ARTHRITIS; LANGERHANS CELLS; KAPPA-B; ACTIVATION; INHIBITION; TOLERANCE AB Triptolide (TPT) is a chemically defined, potent immunosuppressive compound isolated from an anti-inflammatory Chinese herbal. medicine. TPT has been reported to inhibit autoimmunity, allograft rejection, and graft-versus-host disease (GVHD), and its efficacy was previously attributed to the suppression of T cells. Since dendritic cells (DCs) play a major role in the initiation of T-cell-mediated immunity, we studied the effects of TPT on the phenotype, function, and migration of human monocyte-derived DCs. TPT treatment, over a pharmacologic concentration range, inhibited the lipopolysaccharide (LPS)-induced phenotypic changes, characteristic of mature DCs and the production of interieukin-12p(70) (IL-12p(70)). Consequently, the allostimulatory functions of DCs were impaired by TPT treatment. Furthermore, the calcium mobilization and chemotactic responses of LPS-stimulated DCs to secondary lymphoid tissue chemokine (SLC)/CC chemokine ligand 21 (CCL21) were significantly lower in TPT-treated than untreated DCs, in association with lower chemokine receptor 7 (CCR7) and higher CCR5 expression. Egress of Langerhans cells (LCs) from explanted mouse skin in response to macrophage inflammatory protein-3 beta (MIP-3 beta)/CCL19 was arrested by TPT. In vivo administration of TPT markedly inhibited hapten (fluorescein isothiocyanate [FITC])-stimulated migration of mouse skin LCs to the draining lymph nodes. These data provide new insight into the mechanism of action of TPT and indicate that the inhibition of maturation and trafficking of DCs by TPT contributes to its immunosuppressive effects. C1 NCI, BRP, SAIC Frederick Inc, Mol Immunoregulat Lab, Frederick, MD 21702 USA. NCI, Mol Immunoregulat Lab, Ctr Canc Res, Frederick, MD 21702 USA. RP Chen, X (reprint author), NCI, BRP, SAIC Frederick Inc, Mol Immunoregulat Lab, POB B,Bldg 560,Rm 31-19, Frederick, MD 21702 USA. EM xinc@mail.ncifcrf.gov RI Howard, O M Zack/B-6117-2012; Chen, Xin/I-6601-2015 OI Howard, O M Zack/0000-0002-0505-7052; Chen, Xin/0000-0002-2628-4027 FU Intramural NIH HHS; NCI NIH HHS [N01 CO012400, N01-CO-012400] NR 51 TC 32 Z9 39 U1 2 U2 5 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD OCT 1 PY 2005 VL 106 IS 7 BP 2409 EP 2416 DI 10.1182/blood-2005-03-0854 PG 8 WC Hematology SC Hematology GA 968AZ UT WOS:000232134700036 PM 15956285 ER PT J AU Du, Y Spence, SE Jenkins, NA Copeland, NG AF Du, Y Spence, SE Jenkins, NA Copeland, NG TI Cooperating cancer-gene identification through oncogenic-retrovirus-induced insertional mutagenesis SO BLOOD LA English DT Article ID ACUTE MYELOID-LEUKEMIA; TRANSCRIPTION FACTOR; MOUSE; MICE; THERAPY; DIFFERENTIATION; MEDULLOBLASTOMA; ACTIVATION; EXPRESSION; CARCINOMA AB Multiple cooperating mutations that deregulate different signaling pathways are required to induce cancer. Identifying these cooperating mutations is a prerequisite for developing better combinatorial therapies for treating cancer. Here we show that cooperating cancer mutations can be identified through oncogenic-retrovirus-induced insertional mutagenesis. Among 13 myeloid leukemias induced by transplanting into mice bone marrow cells infected in vitro with a replication-defective retrovirus carrying the Sox4 oncogene, 9 contained insertional mutations at known or suspected cancer genes. This likely occurred because rare bone marrow cells, in which the oncogenic retrovirus happened to integrate and in which it mutated a cooperating cancer gene, were selected because the host harbored a cooperating cancer mutation. Cooperativity between Sox4 and another gene, Mef2c, was subsequently confirmed in transplantation studies, in which deregulated Mef2c expression was shown to accelerate the myeloid leukemia induced by Sox4. Insertional mutagenesis of cooperating cancer genes by a defective oncogenic retrovirus provides a new method for identifying cooperating cancer genes and could aid in the development of better therapies for treating cancer. C1 NCI, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21701 USA. RP Copeland, NG (reprint author), NCI, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21701 USA. EM copeland@ncifcrf.gov FU Intramural NIH HHS NR 36 TC 84 Z9 88 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD OCT 1 PY 2005 VL 106 IS 7 BP 2498 EP 2505 DI 10.1182/blood-2004-12-4840 PG 8 WC Hematology SC Hematology GA 968AZ UT WOS:000232134700047 PM 15961513 ER PT J AU Calmels, B Ferguson, C Laukkanen, MO Adler, R Faulhaber, M Kim, HJ Sellers, S Hematti, P Schmidt, M von Kalle, C Akagi, K Donahue, RE Dunbar, CE AF Calmels, B Ferguson, C Laukkanen, MO Adler, R Faulhaber, M Kim, HJ Sellers, S Hematti, P Schmidt, M von Kalle, C Akagi, K Donahue, RE Dunbar, CE TI Recurrent retroviral vector integration at the Mds1/Evi1 locus in nonhuman primate hematopoietic cells SO BLOOD LA English DT Article ID GENE-THERAPY; IN-VIVO; TRANSDUCTION; LEUKEMIA; EVI1; STEM; PROGENITOR; MARKING; CLONES AB Recent reports linking insertional activation of LMO2 following gene therapy for X-linked severe combined immunodeficiency (X-SCID) have led to a re-evaluation of risks following gene therapy with retroviral vectors. In our analysis of 702 integration sites in rhesus macaques that underwent transplantation up to 7 years earlier with autologous CD34(+) cells transduced with amphotropic murine leukemia virus (MLV)-derived retroviral vectors containing marker genes, we detected insertion into one locus, the Mds1/Evi1 region, a total of 14 times in 9 animals. Mds1/Evi1 integrations were observed stably long term, primarily in myeloid cells. We hypothesize that this overrepresentation likely results from an impact on the self-renewal and engraftment potential of CD34(+) progenitor cells via insertional mutagenesis at this specific locus. There is no evidence of ongoing in vivo clonal expansion of the Mds1/Evi1 populations, and all animals are hematologically normal without evidence for leukemia. Characterization of integration sites in this relevant preclinical model provides critical information for gene therapy risk assessment as well as identification of genes controlling hematopoiesis. C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. Chonnam Natl Univ Hosp, Kwangju, South Korea. Univ Freiburg, D-7800 Freiburg, Germany. Childrens Hosp Res Fdn, Cincinnati, OH 45229 USA. NCI, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21701 USA. RP Dunbar, CE (reprint author), NIH, CRC, Bldg 10,Room 4E-5132,10 Ctr Dr, Bethesda, MD 20892 USA. EM dunbarc@nhlbi.nih.gov RI calmels, boris/R-2538-2016 NR 23 TC 121 Z9 124 U1 1 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD OCT 1 PY 2005 VL 106 IS 7 BP 2530 EP 2533 DI 10.1182/blood-2005-03-1115 PG 4 WC Hematology SC Hematology GA 968AZ UT WOS:000232134700052 PM 15933056 ER PT J AU Wu, T Hallett, M AF Wu, T Hallett, M TI A functional MRI study of automatic movements in patients with Parkinson's disease SO BRAIN LA English DT Article DE automatic movement; brain activity; dual task; fMRI; Parkinson's disease ID POSITRON-EMISSION-TOMOGRAPHY; CEREBRAL-BLOOD-FLOW; EXTERNALLY TRIGGERED MOVEMENTS; SUPPLEMENTARY MOTOR AREA; SEQUENTIAL FINGER MOVEMENTS; MONKEY GLOBUS-PALLIDUS; MEDIAL FRONTAL-CORTEX; BASAL GANGLIA; VISUOMOTOR SEQUENCE; CORTICOSPINAL PROJECTIONS AB Patients with Parkinson's disease have great difficulty performing learned movements automatically. The neural contribution to the problem has not been identified. In the current study, we used functional magnetic resonance imaging (fMRI) to investigate the underlying neural mechanisms of movement automaticity in Parkinson's disease patients. Fifteen patients with Parkinson's disease were recruited. Three patients were finally excluded because they could not achieve automaticity. The remaining 12 patients were aged from 52 to 67 years, with a mean age of 61.2 years. Controls included 14 age-matched normal subjects. The subjects were asked to practise four tasks, including two self-initiated, self-paced sequences of finger movements with different complexity until they could perform the tasks automatically. Two dual tasks were used to evaluate automaticity. For dual tasks, subjects performed a visual letter-counting task simultaneously with the sequential movements. Twelve normal subjects performed all sequences automatically. All patients performed sequences correctly; 12 patients could perform the simpler sequence automatically; and only 3 patients could perform the more complex sequence automatically. fMRI results showed that for both groups, sequential movements activated similar brain regions before and after automaticity was achieved. No additional activity was observed in the automatic condition. In normal subjects, many areas had reduced activity at the automatic stage, whereas in patients, only the bilateral superior parietal lobes and left insular cortex were less activated. Patients had greater activity in the cerebellum, premotor area, parietal cortex, precuneus and prefrontal cortex compared with normal subjects while performing automatic movements. We conclude that Parkinson's disease patients can achieve automaticity after proper training, but with more difficulty. Our study is the first to demonstrate that patients with Parkinson's disease require more brain activity to compensate for basal ganglia dysfunction in order to perform automatic movements. C1 NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. Capital Univ Med Sci, Xuanwu Hosp, Dept Neurol, Beijing Inst Geriatr, Beijing, Peoples R China. RP Hallett, M (reprint author), Bldg 10,Rm 5N226,10 Ctr Dr MSC 1428, Bethesda, MD 20892 USA. EM hallettm@ninds.nih.gov FU Intramural NIH HHS NR 91 TC 184 Z9 197 U1 2 U2 21 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD OCT PY 2005 VL 128 BP 2250 EP 2259 DI 10.1093/brain/awh569 PN 10 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 970AW UT WOS:000232278600005 PM 15958505 ER PT J AU Sivakumar, K Kyriakides, T Puls, I Nicholson, GA Funalot, B Antonellis, A Sambuughin, N Christodoulou, K Beggs, JL Zamba-Papanicolaou, E Ionasescu, V Dalakas, MC Green, ED Fischbeck, KH Goldfarb, LG AF Sivakumar, K Kyriakides, T Puls, I Nicholson, GA Funalot, B Antonellis, A Sambuughin, N Christodoulou, K Beggs, JL Zamba-Papanicolaou, E Ionasescu, V Dalakas, MC Green, ED Fischbeck, KH Goldfarb, LG TI Phenotypic spectrum of disorders associated with glycyl-tRNA synthetase mutations SO BRAIN LA English DT Article DE Charcot-Marie-Tooth disease; distal spinal muscular atrophy; genotype-phenotype relationships; glycyl-tRNA synthetase; hand-predominant muscle atrophy ID SPINAL MUSCULAR-ATROPHY; MARIE-TOOTH-DISEASE; SENSORY NEURON DISEASES; ELECTROPHYSIOLOGIC FINDINGS; MOTOR NEUROPATHIES; SILVER-SYNDROME; CHROMOSOME 7P; CMT2D; FIBERS; BSCL2 AB We describe clinical, electrophysiological, histopathological and molecular features of a unique disease caused by mutations in the glycyl-tRNA synthetase (GARS) gene. Sixty patients from five multigenerational families have been evaluated. The disease is characterized by adolescent onset of weakness, and atrophy of thenar and first dorsal interosseus muscles progressing to involve foot and peroneal muscles in most but not all cases. Mild to moderate sensory deficits develop in a minority of patients. Neurophysiologically confirmed chronic denervation in distal muscles with reduced compound motor action potentials were features consistent with both motor neuronal and axonal pathology. Sural nerve biopsy showed mild to moderate selective loss of small- and medium-sized myelinated and small unmyelinated axons, although sensory nerve action potentials were not significantly decreased. Based on the presence or absence of sensory changes, the disease phenotype was initially defined as distal spinal muscular atrophy type V (dSMA-V) in three families, Charcot-Marie-Tooth disease type 2D (CMT2D) in a single family, and as either dSMA-V or CMT2D in patients of another large family. Linkage to chromosome 7p15 and the presence of disease-associated heterozygous GARS mutations have been identified in patients from each of the five studied families. We conclude that patients with GARS mutations present a clinical continuum of predominantly motor distal neuronopathy/axonopathy with mild to moderate sensory involvement that varies between the families and between members of the same family. Awareness of these overlapping clinical phenotypes associated with mutations in GARS will facilitate identification of this disorder in additional families and direct future research toward better understanding of its pathogenesis. C1 NINDS, NIH, Bethesda, MD 20892 USA. Barrow Neurol Inst, Phoenix, AZ 85013 USA. Cyprus Inst Neurol & Genet, Nicosia, Cyprus. NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. Univ Sydney, Concord Hosp, ANZAC Res Inst, Concord, Australia. Hop St Anne, Ctr Paul Broca, INSERM, U573, F-75674 Paris, France. Univ Iowa, Dept Pediat, Div Med Genet, Iowa City, IA 52242 USA. RP Goldfarb, LG (reprint author), NINDS, NIH, 5625 Fisheres Lane,Room 4S06, Bethesda, MD 20892 USA. EM goldfarbl@ninds.nih.gov NR 36 TC 68 Z9 71 U1 1 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD OCT PY 2005 VL 128 BP 2304 EP 2314 DI 10.1093/brain/awh590 PN 10 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 970AW UT WOS:000232278600011 PM 16014653 ER PT J AU Olive, M Goldfarb, LG Shatunov, A Fischer, D Ferrer, I AF Olive, M Goldfarb, LG Shatunov, A Fischer, D Ferrer, I TI Myotilinopathy: refining the clinical and myopathological phenotype SO BRAIN LA English DT Article DE LGMD1A; myofibrillar myopathy; myotilin; MYOT mutations; phenotype ID GIRDLE MUSCULAR-DYSTROPHY; DESMIN-RELATED MYOPATHY; INCLUSION-BODY MYOSITIS; MYOFIBRILLAR MYOPATHY; CLUSTERIN; MUTATIONS; PROTEIN; LGMD1A; GENE; EXPRESSION AB Mutations in myotilin gene (MYOT) have been associated with variable syndromes including limb girdle muscular dystrophy type 1A (LGMD1A) and a subgroup of myofibrillar myopathy (MFM/MYOT). We studied six Spanish patients from three unrelated kindreds and seven patients without family history. Three previously reported and two novel disease-associated MYOT mutations were identified in this group of patients. The disease is characterized by the onset at the age of 42-77 years with muscle weakness initially in distal or proximal leg muscles, eventually spreading to other muscle groups of the lower and upper extremities. Associated signs of cardiomyopathy, respiratory failure and peripheral neuropathy are present in a fraction of patients. Myopathological features of focal myofibrillar destruction resulting in intracytoplasmic deposits, strongly immunoreactive to myotilin, multiple rimmed and centrally or subsarcolemmally located non-rimmed vacuoles and streaming Z-lines, were observed in each patient studied. The Spanish cohort, the largest group of patients studied so far, shares phenotypic features with both LGMD1A and MFM/MYOT variants thus establishing a continuum of phenotypic manifestations characteristic of myotilinopathy, an emerging neuromuscular disorder. C1 Bellvitge Hosp, IDIBELL, Inst Neuropatol, Barcelona 08907, Spain. NINDS, NIH, Bethesda, MD 20892 USA. Univ Bonn, Dept Neurol, Muskellabor, D-53105 Bonn, Germany. RP Olive, M (reprint author), Bellvitge Hosp, IDIBELL, Inst Neuropatol, C Feixa Llarga S-N, Barcelona 08907, Spain. EM 25169mop@comb.es RI Shatunov, Aleksey/E-6946-2011; OI Olive, Montse/0000-0001-5727-0165 NR 24 TC 84 Z9 85 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 2005 VL 128 BP 2315 EP 2326 DI 10.1093/brain/awh576 PN 10 PG 12 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 970AW UT WOS:000232278600012 PM 15947064 ER PT J AU Srinivasan, R Balow, JE Sabnis, S Lundqvist, A Igarashi, T Takahashi, Y Austin, H Tisdale, J Barrett, J Geller, N Childs, R AF Srinivasan, R Balow, JE Sabnis, S Lundqvist, A Igarashi, T Takahashi, Y Austin, H Tisdale, J Barrett, J Geller, N Childs, R TI Nephrotic syndrome: an under-recognised immune-mediated complication of non-myeloablative allogeneic haematopoietic cell transplantation SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE stem cell transplantation; nephrotic syndrome; membranous glomerulonephritis; non-myeloablative stem cell transplantation ID VERSUS-HOST-DISEASE; BONE-MARROW-TRANSPLANTATION; MEMBRANOUS NEPHROPATHY; CYCLOSPORINE WITHDRAWAL; PARANEOPLASTIC GLOMERULOPATHIES; T-CELLS; RECIPIENT; GLOMERULONEPHRITIS; MANIFESTATION; PATIENT AB Nephrotic syndrome (NS)is an extremely rare complication of myeloablative allogeneic haematopoietic cell transplantation (HCT) that usually occurs in association with chronic graft-versus-host disease (C-GVHD). We observed an unexpectedly high incidence of NS in a cohort of 163 consecutive patients undergoing non-myeloablative HCT from a related human leucocyte antigen-compatible donor. Seven patients developed NS at a median 318 d post-transplant (range 119-1203 d; cumulative incidence 6.1%). The median age at onset of NS was 46 years (range 33-59 years); three of the seven patients had no evidence of C-GVHD while four had accompanying limited C-GVHD. At diagnosis, median proteinuria was 16.5 g/24 h (range 3-24 g/ 24 h). Renal biopsy was performed in four cases and revealed membranous nephropathy. NS was not always associated with other symptoms of C-GVHD, and in contrast to previous reports, usually did not improve with the re- initiation of aggressive immunosuppression, resulting in progressive renal failure necessitating dialysis in three of seven cases. Membranous nephropathy resulting in NS is a previously unrecognised and clinically significant complication of non-myeloablative HCT. C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. NIDDK, Bethesda, MD USA. Armed Forces Inst Pathol, Washington, DC 20306 USA. NHLBI, Off Biostat, Bethesda, MD 20892 USA. RP Childs, R (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10,Rm 7C103,MSC 1652,9000 Rockville Pike, Bethesda, MD 20892 USA. EM childsr@nih.gov RI Takahashi, Yoshiyuki/I-1929-2012; OI Lundqvist, Andreas/0000-0002-9709-2970 NR 37 TC 44 Z9 49 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD OCT PY 2005 VL 131 IS 1 BP 74 EP 79 DI 10.1111/j.1365-2141.2005.05728.x PG 6 WC Hematology SC Hematology GA 965WE UT WOS:000231980800011 PM 16173966 ER PT J AU Pacher, P Batkai, S Kunos, G AF Pacher, P Batkai, S Kunos, G TI Cirrhotic cardiomyopathy: an endocannabinoid connection? SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Editorial Material ID RECEPTORS; CANNABINOIDS; MACROPHAGES; PRESSURE C1 NIAAA, LPS, NIH, Bethesda, MD 20892 USA. RP Pacher, P (reprint author), NIAAA, LPS, NIH, 5625 Fishers Lane,MSC-9413, Bethesda, MD 20892 USA. EM pacher@mail.nih.gov; gkunos@mail.nih.gov RI Batkai, Sandor/G-3889-2010; Pacher, Pal/B-6378-2008; Batkai, Sandor/H-7983-2014 OI Pacher, Pal/0000-0001-7036-8108; FU Intramural NIH HHS [Z01 AA000375-02, Z99 AA999999] NR 13 TC 13 Z9 13 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD OCT PY 2005 VL 146 IS 3 BP 313 EP 314 DI 10.1038/sj.bjp.0706332 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 970NR UT WOS:000232317400001 PM 16025137 ER PT J AU Devi, PU Satyamitra, M AF Devi, PU Satyamitra, M TI Tracing radiation induced genomic instability in vivo in the haemopoietic cells from fetus to adult mouse SO BRITISH JOURNAL OF RADIOLOGY LA English DT Article ID DELAYED REPRODUCTIVE DEATH; CHROMOSOMAL INSTABILITY; FETAL IRRADIATION; OXIDATIVE STRESS; X-IRRADIATION; CONSEQUENCES; TRANSMISSION; ABERRATIONS; MUTATIONS; CULTURES AB The present experiment was aimed at studying the delayed expression of fetal irradiation induced genomic instability in the mouse haemopoietic cells in vivo. The abdominal area of 14 day pregnant Swiss albino mice was exposed to 0-1.5 Gy of gamma radiation. Chromosomal aberrations were studied in three passages of spleen colonies (short-term repopulating stem cells, STRSC) derived from 24 h post-irradiation fetal liver cells and in the 1-20 months postpartum bone marrow (long-term repopulating stem cells, LTRSC). Irradiation produced a significant and dose-dependent increase in the aberrant metaphases in the first passage spleen colony (CFU-S1) cells, which decreased in subsequent passages and reached normal levels by the third passage (CFU-S3). Bone marrow at 1-6 months postpartum showed similar chromosomal picture in the 0 Gy control and after 0.5-1.5 Gy, but there was a clear increase in aberrant cells from 9 months postpartum in the irradiated groups. Some mice in all irradiated groups showed a 2.5- to 5-fold increase in peripheral leukocyte counts. Bone marrow of these animals exhibited severe aneuploidy, the chromosome number ranging from less than 1n to 6n at 20 months of age. Our results indicate that unstable chromosome aberrations induced in the fetal haemopoietic STRSC are eliminated during subsequent cell divisions. However, genomic instability induced in the LTRSC persists and is expressed as chromosomal aberrations at advanced ages. Induction of chromosome aneuploidy could be an early step in the chain of events leading to adult leukaemia after prenatal irradiation. C1 Jawaharlal Nehru Canc Hosp & Res Ctr, Dept Res, Bhopal 462001, India. RP Devi, PU (reprint author), NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA. NR 30 TC 13 Z9 14 U1 0 U2 1 PU BRITISH INST RADIOLOGY PI LONDON PA 36 PORTLAND PLACE, LONDON W1N 4AT, ENGLAND SN 0007-1285 J9 BRIT J RADIOL JI Br. J. Radiol. PD OCT PY 2005 VL 78 IS 934 BP 928 EP 933 DI 10.1259/bjr/18119329 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 976EQ UT WOS:000232716000010 PM 16177016 ER PT J AU Amrein, PC Clark, JR Supko, JG Fabian, RL Wang, CC Colevas, AD Posner, MR Deschler, DG Rocco, JW Finkelstein, DM McIntyre, JF AF Amrein, PC Clark, JR Supko, JG Fabian, RL Wang, CC Colevas, AD Posner, MR Deschler, DG Rocco, JW Finkelstein, DM McIntyre, JF TI Phase I trial and pharmacokinetics of escalating doses of paclitaxel and concurrent hyperfractionated radiotherapy with or without amifostine in patients with advanced head and neck carcinoma SO CANCER LA English DT Article; Proceedings Paper CT 37th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 12-15, 2001 CL SAN FRANCISCO, CA SP Amer Soc Clin Oncol DE amifostine; paclitaxel; head and neck carcinoma; accelerated; hyper-fractionated; radiotherapy; pharmacokinetics ID SQUAMOUS-CELL CARCINOMA; CYTOPROTECTIVE AGENT AMIFOSTINE; LOCALLY ADVANCED HEAD; RADIATION-THERAPY; INDUCTION CHEMOTHERAPY; RANDOMIZED-TRIAL; SINGLE-AGENT; ACTIVE-DRUG; STAGE-III; CANCER AB BACKGROUND. Arnifostine was developed to protect normal tissues from radiation exposure. The current study was undertaken to determine whether arnifostine would allow the delivery of greater numbers of weekly paclitaxel treatments with concomitant, hyperfractionated radiotherapy in patients with advanced head and neck carcinoma. METHODS. Patients received radiation therapy twice daily using 1.6-gray (Gy) fractions up to a total of 70.4 Gy over an elapsed time of 6.5 weeks. All patients received paclitaxel 60 mg/m(2) once weekly starting on Day 1. The number of doses of paclitaxel was escalated from three to a maximum of six in groups of three patients. For the patients who received armfostine, a dose of 400 mg/m(2) was given intravenously over 15 minutes on Days 1-5, 8, 29-33, and 36. Patients under-went surgery for persistent tumor after radiotherapy. The plasma pharmacokinetics of paclitaxel were characterized during treatment with the first weekly dose to determine the effect of concurrently administered amifostine. RESULTS. Thirty-six patients were evaluable for this study. In the absence of amifostine, a maximum of four doses of paclitaxel were tolerated in combination with the radiotherapy. With amifostine, up to five doses of paclitaxel could be given. Generally, the treatment resulted in Grade 2 and 3 stomatitis. Overall, 69% of patients had a complete remission, and 29% had a partial remission. Both progression-free survival and overall survival were 66% at 30 months. Amifostine had no effect on the pharmacokinetics of paclitaxel. CONCLUSIONS. The administration of armfostine allowed the authors to give an additional dose of paclitaxel to patients who were undergoing hyperfractionated. radiotherapy for head and neck carcinoma. This treatment regimen resulted in a high frequency of complete remissions and an excellent progression -free survival pattern without compromising the plasma kinetics of paclitaxel. C1 Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Dept Surg, Boston, MA 02114 USA. Natl Canc Inst, Rockville, MD USA. Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. N Shore Canc Ctr Peabody, Boston, MA USA. RP Amrein, PC (reprint author), Massachusetts Gen Hosp, Dept Med, Tawkey 7942, Boston, MA 02114 USA. EM pamrein@partners.org NR 55 TC 5 Z9 6 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD OCT 1 PY 2005 VL 104 IS 7 BP 1418 EP 1427 DI 10.1002/cncr.21312 PG 10 WC Oncology SC Oncology GA 966EA UT WOS:000232001200011 PM 16116597 ER PT J AU Posadas, EM Gulley, J Arlen, PM Trout, A Parnes, HI Wright, J Lee, MJ Chung, EJ Trepel, JB Sparreboom, A Chen, C Jones, E Steinberg, SM Daniels, A Figg, WD Dahut, WL AF Posadas, EM Gulley, J Arlen, PM Trout, A Parnes, HI Wright, J Lee, MJ Chung, EJ Trepel, JB Sparreboom, A Chen, C Jones, E Steinberg, SM Daniels, A Figg, WD Dahut, WL TI A phase II study of perifosine in androgen independent prostate cancer SO CANCER BIOLOGY & THERAPY LA English DT Article DE perifosine; prostate cancer; pharmacokinetics; circulating tumor cells; targeted therapy ID METASTATIC BREAST-CANCER; CIRCULATING TUMOR-CELLS; SOLID TUMORS; CLINICAL-TRIALS; EXPRESSION; MITOXANTRONE; PREDNISONE; ACTIVATION; GUIDELINES; DOCETAXEL AB Objectives. Perifosine is an alkylphospholipid that has exhibited broad antineoplastic activity in preclinical studies. The primary objective of this study was to determine the clinical efficacy of this agent in the treatment of androgen-independent prostate cancer (AIPC) using PSA and clinical criteria. Patients and Methods. Nineteen patients with progressive, metastatic AIPC were treated with oral perifosine. Cycles were 28 days in length. A loading dose of 900 mg was given on day 1 of cycle 1 followed by a maintenance dose of 150 mg daily for the next 20 days. A loading dose of 600 mg was administered on the first day of subsequent cycles by the maintenance dose of 150 mg daily for the next 20 days. Pharmacokinetic measurements were made throughout the course of the study. Circulating epithelial cells were collected via leukapheresis on day 0, 3, and 28. Results. Median patient age was 67 years and median PSA was 180 ng/mL ( range: 19-904 ng/ml). Grade 1-2 fatigue and gastrointestinal toxicities were common. Pharmacokinetic studies showed an average minimum concentration at steady-state of approximately 4059 ng/ml which correlated well with previous studies. Median time to progression was four weeks. There were no radiographic responses or PSA declines of 50% or greater related to perifosine. Conclusions. Treatment with perifosine was complicated by fatigue and gastrointestinal toxicity. No significant clinical activity against prostate cancer was observed. This agent does not merit further study in the setting of monotherapy in this population. C1 NCI, Ctr Canc Res, Med Oncol Clin Res Unit, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, Biostat & Data Management Sect, Bethesda, MD 20892 USA. RP Dahut, WL (reprint author), Bldg 10,Rm 12N226,10 Ctr Dr, Bethesda, MD 20892 USA. EM dahutw@mail.nih.gov RI Sparreboom, Alex/B-3247-2008; Gulley, James/K-4139-2016; Figg Sr, William/M-2411-2016 OI Gulley, James/0000-0002-6569-2912; NR 26 TC 65 Z9 70 U1 2 U2 3 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD OCT PY 2005 VL 4 IS 10 BP 1133 EP 1137 PG 5 WC Oncology SC Oncology GA 022GO UT WOS:000236043700021 PM 16138006 ER PT J AU Belova, GI Demidov, ON Fornace, AJ Bulavin, DV AF Belova, GI Demidov, ON Fornace, AJ Bulavin, DV TI Chemical inhibition of Wip1 phosphatase contributes to suppression of tumorigenesis SO CANCER BIOLOGY & THERAPY LA English DT Article DE Wip1 phosphatase; inhibitors; tumorigenesis; cancer; suppression; therapy ID TUMOR-SUPPRESSOR; UV-RADIATION; PPM1D; AMPLIFICATION; CANCER; ACTIVATION; GAIN; P53 AB Wip1 is an amplified oncogene whose deletion causes a tumor resistant phenotype in mice. These observations provide justification for a search for Wip1 chemical inhibitors as potential anticancer drugs. Here we report a group of Wip1 inhibitors with anticancer properties both in vitro and in vivo. In vitro, inactivation of Wip1 reduces the proliferation rate of breast cancer cell lines and enhances growth inhibition caused by doxorubicin. In vivo, administration of Wip1 inhibitors decreases proliferation of xenograph tumors and tumors developed in MMTV-c-Neu transgenic mice. We propose that these agents may serve as lead compounds for the development of anticancer drugs targeting Wip1 phosphatase. C1 NCI, Ctr Canc Res, NIH, Bethesda, MD USA. Inst Mol & Cell Biol, Cell Cycle Control & Tumorigenesis Grp, Singapore, Singapore. RP Bulavin, DV (reprint author), 61 Biopolis Dr,Proteos 5-13, Singapore 138673, Singapore. EM dvbulavin@imcb.a-star.edu.sg RI Fornace, Albert/A-7407-2008; ASTAR, IMCB/E-2320-2012; OI Fornace, Albert/0000-0001-9695-085X; Demidov, Oleg/0000-0003-4323-7174 NR 17 TC 48 Z9 50 U1 0 U2 9 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD OCT PY 2005 VL 4 IS 10 BP 1154 EP 1158 PG 5 WC Oncology SC Oncology GA 022GO UT WOS:000236043700024 PM 16258255 ER PT J AU Rogers, BE Roberson, PL Shen, S Khazaeli, MB Carpenter, M Yokoyama, S Brechbiel, MW LoBuglio, AF Buchsbaum, DJ AF Rogers, BE Roberson, PL Shen, S Khazaeli, MB Carpenter, M Yokoyama, S Brechbiel, MW LoBuglio, AF Buchsbaum, DJ TI Intraperitoneal radioimmunotherapy with a humanized anti-TAG-72 (CC49) antibody with a deleted CH2 region SO CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS LA English DT Article DE TAG-72; lutetium-177; CC49; dosimetry; pharmacokinetics; therapy ID SINGLE-CHAIN FV; HIGH-DOSE THERAPY; PHASE-I TRIAL; MONOCLONAL-ANTIBODY; GLYCOPROTEIN TAG-72; TUMOR PENETRATION; IMMUNE-RESPONSE; OVARIAN-CANCER; BONE-MARROW; BIODISTRIBUTION AB The application of intraperitoneal (i.p.) radioimmunotherapy to treat i.p. tumor loci has been limited by bone marrow toxicity secondary to circulating radiolabeled antibodies. The generation of novel genetically engineered monoclonal antibodies, which can achieve high tumor uptake and rapid blood clearance, should enhance the therapeutic index of i.p. radioimmunotherapy. In this regard, a novel humanized anti-TAG-72 monoclonal antibody with a deleted CH2 region (HuCC49 Delta CH2) has been described, which localized well to subcutaneous xenograft tumors and had a rapid plasma clearance. The aim of this study was to examine the characteristics of this radiolabeled reagent when administered through the i.p. route in mice bearing i.p. tumor (LS174T). The Delta CH2 molecule and intact humanized CC49 (HuCC49) monoclonal antibody were conjugated to PA-DOTA and radiolabeled with Lu-177. Both molecules retained high-affinity binding to TAG-72 positive LS174T tumor cells in vitro. The radiolabeled Delta CH2 molecule had a modest decrease in tumor localization, as compared to the intact molecule when administered i.p. to tumor-bearing mice and a dramatically shorter plasma disappearance T-1/2 at 2.7 hours compared to 61.2 hours for the intact antibody. The radiolabeled Delta CH2 molecule thus had very high tumor:blood ratios. Using an I-131-labeled system, the maximum tolerated dose of Delta CH2 was > 3X that of intact HuCC49. Autoradiography of tumors showed low radiation dose rates at tumor centers early (I and 4 hours), as compared to higher dose rates at tumor periphery but a more uniform distribution by 24 hours. Dose-rate distributions were similar for both reagents. Animals bearing LS174T i.p. tumors were treated with 300 mu Ci of Lu-177-labeled Delta CH2 or intact HuCC49 by i.p. route daily X 3. The Lu-177-Delta CH2 molecule mediated an increase in median survival compared to controls (67.5 +/- 7.5 days versus controls of 32 +/- 3.3) while the same dose of Lu-177-HuCC49 produced early toxic deaths. These studies suggest that i.p. radioimmunotherapy using radiolabeled HuCC49 Delta CH2 should allow higher radiation doses to be administered with less marrow toxicity and potentially improved efficacy. C1 Univ Alabama, Dept Radiat Oncol, Birmingham, AL 35294 USA. Univ Alabama, Dept Med, Birmingham, AL 35294 USA. Univ Michigan, Dept Radiat Oncol, Ann Arbor, MI 48109 USA. NCI, Radioimmune & Inorgan Chem Sect, NIH, Bethesda, MD 20892 USA. RP Buchsbaum, DJ (reprint author), Univ Alabama, Dept Radiat Oncol, 1824 6th Ave S,WTI 674, Birmingham, AL 35294 USA. EM djb@uab.edu FU NCI NIH HHS [1P50 CA 83591] NR 38 TC 13 Z9 13 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1084-9785 J9 CANCER BIOTHER RADIO JI Cancer Biother. Radiopharm. PD OCT PY 2005 VL 20 IS 5 BP 502 EP 513 DI 10.1089/cbr.2005.20.502 PG 12 WC Oncology; Medicine, Research & Experimental; Pharmacology & Pharmacy; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Research & Experimental Medicine; Pharmacology & Pharmacy; Radiology, Nuclear Medicine & Medical Imaging GA 982EK UT WOS:000233140500005 PM 16248766 ER PT J AU Milenic, DE Garmestani, K Brady, ED Albert, PS Ma, DS Abdulla, A Brechbiel, MW AF Milenic, DE Garmestani, K Brady, ED Albert, PS Ma, DS Abdulla, A Brechbiel, MW TI alpha-particle radioimmunotherapy of disseminated peritoneal disease using a Pb-212-labeled radioimmunoconjugate targeting HER2 SO CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS LA English DT Article DE radioimmunotherapy; alpha-particle; lead; Pb-212; Herceptin; HER2 ID SINGLE-CHAIN FV; MONOCLONAL-ANTIBODY; FRACTIONATED RADIOIMMUNOTHERAPY; IN-VIVO; EMITTING RADIONUCLIDES; I-131-LYM-1 ANTIBODY; CARCINOMA XENOGRAFTS; CANCER; THERAPY; BIODISTRIBUTION AB These studies demonstrate the feasibility of targeted therapy for the treatment of disseminated peritoneal disease using Pb-212-labeled Herceptin as an in vivo generator of Bi-212. In vitro studies compare the potential of the bismuth radioisotopes, Bi-213 and Bi-212, to that of Pb-212. Overall, Pb-212 results in a higher therapeutic index than either bismuth radioisotope, requiring lower radioactivity (mu Ci) for effective cytotoxic response. A pilot radioimmunotherapy (RIT) experiment treating mice bearing 5 d LS-174T intraperitoneally (i.p.) xenogrqfts determined a maximum tolerated dose (MTD) of 20-40 mu Ci with i.p. administration. A specific dose response was observed and 10 mu Ci was selected as the effective operating dose for future experiments. Median survival of tumor-bearing mice receiving 10 mu Ci increased from 19 to 56 days (p = 0.008). The efficacy of Pb-212-Herceptin was also assessed in a human pancreatic carcinoma xenograft (Shaw; i.p.) animal model previously reported as unresponsive to Bi-213-Herceptin (p = 0.002). Multiple dosing of Pb-212-Herceptin was evaluated in both animal models. The median survival of mice bearing 3 d LS-174T i.p. xenografts increased to 110 days, with tip to 3 doses of Pb-212-Herceptin given at approximately. monthly intervals; however, there was no evidence of a correlation with the second and third doses (p = 0.98). No improvement in median. survival was noted with a similar regimen in the Shaw xenograft model. C1 NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. NCI, Biometr Res Branch, Bethesda, MD 20892 USA. RP Milenic, DE (reprint author), NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, NIH, 10 Ctr Dr,MSC 1088,Bldg 10,Room 1B40, Bethesda, MD 20892 USA. EM dm71q@nih.gov NR 42 TC 54 Z9 56 U1 1 U2 8 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1084-9785 J9 CANCER BIOTHER RADIO JI Cancer Biother. Radiopharm. PD OCT PY 2005 VL 20 IS 5 BP 557 EP 568 DI 10.1089/cbr.2005.20.557 PG 12 WC Oncology; Medicine, Research & Experimental; Pharmacology & Pharmacy; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Research & Experimental Medicine; Pharmacology & Pharmacy; Radiology, Nuclear Medicine & Medical Imaging GA 982EK UT WOS:000233140500010 PM 16248771 ER PT J AU Given, LS Black, B Lowry, G Huang, P Kerner, JF AF Given, LS Black, B Lowry, G Huang, P Kerner, JF TI Collaborating to conquer cancer: a comprehensive approach to cancer control SO CANCER CAUSES & CONTROL LA English DT Article; Proceedings Paper CT Conference on Comprehensive Approaches to Cancer Control CY SEP, 2003 CL Atlanta, GA DE comprehensive cancer control; cancer burden; national cancer partners AB Despite substantial contributions on the part of public, non-profit, and private sector organizations, the burden of cancer in the United States remains high. As public health organizations, particularly county, state, tribal, and territorial health departments, try to reduce the significant burden of cancer, they face additional issues that make it difficult to address cancer in a comprehensive way. These challenges along with the need to accelerate progress in reducing the U.S. cancer burden, prompted the Centers for Disease Control and Prevention (CDC) and its national partners to begin to work together to further define and describe comprehensive cancer control (CCC) as an approach to reducing the burden of cancer. CCC is defined as "an integrated and coordinated approach to reducing cancer incidence, morbidity, and mortality through prevention, early detection, treatment, rehabilitation, and palliation." This article describes the national effort to support comprehensive cancer control, outlines national and state level success in comprehensive cancer control, and provides a call to action to public, private, and non-profit organizations, governments of all levels, and individuals to renew their commitments to reducing the burden of cancer. C1 Ctr Dis Control & Prevent, Program Serv Branch, Div Canc Prevent & Control, Atlanta, GA 30341 USA. Amer Canc Soc, Atlanta, GA 30329 USA. Ctr Dis Control & Prevent, Program Serv Branch, Div Canc Prevent & Control, Olympia, WA USA. Texas Dept State Hlth Serv, Hlth Promot Unit, Austin, TX USA. NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Given, LS (reprint author), Ctr Dis Control & Prevent, Program Serv Branch, Div Canc Prevent & Control, 4770 Buford Highway NE,Mailstop K-57, Atlanta, GA 30341 USA. EM lgiven@cdc.gov OI Kerner, Jon/0000-0002-8792-3830 NR 21 TC 19 Z9 19 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD OCT PY 2005 VL 16 SU 1 BP 3 EP 14 DI 10.1007/s10552-005-0499-8 PG 12 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 990GP UT WOS:000233731500002 PM 16208570 ER PT J AU Kerner, JF Guirguis-Blake, J Hennessy, KD Brounstein, PJ Vinson, C Schwartz, RH Myers, BA Briss, P AF Kerner, JF Guirguis-Blake, J Hennessy, KD Brounstein, PJ Vinson, C Schwartz, RH Myers, BA Briss, P TI Translating research into improved outcomes in comprehensive cancer control SO CANCER CAUSES & CONTROL LA English DT Article; Proceedings Paper CT Conference on Comprehensive Approaches to Cancer Control CY SEP, 2003 CL Atlanta, GA DE dissemination; implementation; knowledge transfer; comprehensive cancer control ID PREVENTIVE-SERVICES; INTERVENTIONS; CHALLENGES; PROGRAM; CARE AB A key question in moving comprehensive cancer control (CCC) plans into action is, to what extent should the knowledge gained from investments in cancer prevention and control research influence the actions taken by states, tribes, and territories during implementation? Underlying this 'should' is the assumption that evidence-based approaches (i.e., a public health or clinical intervention or policy that has resulted in improved outcomes when scientifically tested), when implemented in a real-world setting, will increase the likelihood of improved outcomes. This article elucidates the barriers and opportunities for integrating science with practice across the cancer control continuum. However, given the scope of CCC and the substantial investment in generating new knowledge through science, it is difficult for any one agency, on its own, to make a sufficient investment to ensure new knowledge is translated and implemented at a national, state, or local level. Thus, if greater demand for evidence-based interventions and increased resources for adopting them are going to support the dissemination initiatives described herein, new interagency partnerships must be developed to ensure that sufficient means are dedicated to integrating science with service. Furthermore, for these collaborations to increase both in size and in frequency, agency leaders must clearly articulate their support for these collaborative initiatives and explicitly recognize those collaborative efforts that are successful. In this way, the whole (in this context, comprehensive cancer control) can become greater than the sum of its parts. C1 NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Agcy Healthcare Res & Qual, Rockville, MD USA. Subst Abuse & Mental Hlth Serv Adm, Rockville, MD USA. Amer Canc Soc, Framingham, MA USA. Ctr Dis Control & Prevent, Atlanta, GA USA. RP Kerner, JF (reprint author), NCI, Div Canc Control & Populat Sci, 6130 Execut Blvd,EPN 6144, Bethesda, MD 20892 USA. EM kernerj@mail.nih.gov OI Kerner, Jon/0000-0002-8792-3830 NR 30 TC 49 Z9 50 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD OCT PY 2005 VL 16 SU 1 BP 27 EP 40 DI 10.1007/s10552-005-0488-y PG 14 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 990GP UT WOS:000233731500004 PM 16208572 ER PT J AU Pollack, LA Greer, GE Rowland, JH Miller, A Doneski, D Coughlin, SS Stovall, E Ulman, D AF Pollack, LA Greer, GE Rowland, JH Miller, A Doneski, D Coughlin, SS Stovall, E Ulman, D TI Cancer survivorship: a new challenge in comprehensive cancer control SO CANCER CAUSES & CONTROL LA English DT Article; Proceedings Paper CT Conference on Comprehensive Approaches to Cancer Control CY SEP, 2003 CL Atlanta, GA DE neoplasms/epidemiology; public health practice; quality of life; survivors ID PHYSICAL-ACTIVITY; SURVIVAL RATES; SOCIETY GUIDE; LUNG-CANCER; HEALTH; CARE; DIAGNOSIS; NUTRITION; MORTALITY; PROSTATE AB Cancer survivors are a growing population in the United States because of earlier cancer diagnosis, the aging of society, and more effective risk reduction and treatment. Concerns about the long-term physical, psychosocial, and economic effects of cancer treatment on cancer survivors and their families are increasingly being recognized and addressed by public, private, and non-profit organizations. The purpose of this paper is to discuss how survivorship fits within the framework of comprehensive cancer control. We summarize three national reports on cancer survivorship and highlight how various organizations and programs are striving to address the needs of cancer survivors through public health planning, including the challenges these groups face and the gaps in knowledge and available services. As cancer survivorship issues are being recognized, many organizations have objectives and programs to address concerns of those diagnosed with cancer. However, better coordination and dissemination may decrease overlap and increase the reach of efforts and there is limited evidence for the effectiveness and impact of these efforts. C1 Ctr Dis Control & Prevent, Div Canc Prevent & Control, Atlanta, GA 30341 USA. NCI, Off Canc Survivorship, NIH, Bethesda, MD 20892 USA. Natl Coalit Canc Survivorship, Silver Spring, MD USA. Lance Armstrong Fdn, Austin, TX USA. Amer Canc Soc, Atlanta, GA 30329 USA. RP Pollack, LA (reprint author), Ctr Dis Control & Prevent, Div Canc Prevent & Control, 4770 Buford Hwy NE,Mailstop K-55, Atlanta, GA 30341 USA. EM lpollack@cdc.gov NR 49 TC 40 Z9 42 U1 1 U2 8 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD OCT PY 2005 VL 16 SU 1 BP 51 EP 59 DI 10.1007/s10552-005-0452-x PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 990GP UT WOS:000233731500006 PM 16208574 ER PT J AU Purdue, MP Mink, PJ Hartge, P Huang, WY Buys, S Hayes, RB AF Purdue, MP Mink, PJ Hartge, P Huang, WY Buys, S Hayes, RB TI Hormone replacement therapy, reproductive history, and colorectal adenomas: Data from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial (United states) SO CANCER CAUSES & CONTROL LA English DT Article DE adenoma; colorectal neoplasms; hormone replacement therapy; mass screening ID LARGE-BOWEL-CANCER; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; COLON-CANCER; POSTMENOPAUSAL WOMEN; ESTROGEN-RECEPTOR; RISK-FACTORS; PROGESTERONE-RECEPTORS; CALCIUM-ABSORPTION; EXOGENOUS HORMONES; ENDOTHELIAL-CELLS AB Objective: Findings from some epidemiologic studies of colorectal cancer and adenoma suggest that the protective effect of post-menopausal hormone replacement therapy (HRT) may differ across categories of age and body mass index (BMI). We conducted an analysis of women participating in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial to investigate the relationship between HRT use and prevalent adenoma, both overall and across different population subgroups. Methods: Women aged 55-74 were randomized to screening by flexible sigmoidoscopy at ten PLCO screening centers between September 1993 and September 2001. We identified 1468 women with at least one left-sided adenoma and 19,203 without adenoma or colorectal cancer. Information about HRT and reproductive factors was obtained from a self-administered questionnaire. Results: Compared to never use of HRT, current use was associated with a decreased prevalence of left-sided adenoma (odds ratio (OR) 0.85; 95% confidence interval (CI) 0.75-0.97). We found no evidence of dose-response with increasing duration of use for current or former users. The association with current HRT use was stronger among women aged 65+ (OR 0.69; 95% CI 0.56-0.84), with a BMI < 30 (OR 0.82; 95% CI 0.71-0.95) and who regularly use aspirin or ibuprofen (OR 0.77; 95% CI 0.65-0.91). Other reproductive factors were not significantly associated with adenoma prevalence. Conclusions: Our findings suggest that current HRT use may protect against colorectal adenoma, and that this protective effect is short-lived following cessation of use. C1 NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20892 USA. NCI, Div Canc Prevent, Rockville, MD USA. Univ Utah, Hlth Sci Ctr, Salt Lake City, UT USA. RP Purdue, MP (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,MSC 7240,Execut Plaza S 8121, Rockville, MD 20892 USA. EM purduem@mail.nih.gov RI Purdue, Mark/C-9228-2016; OI Purdue, Mark/0000-0003-1177-3108; Hayes, Richard/0000-0002-0918-661X NR 48 TC 23 Z9 23 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD OCT PY 2005 VL 16 IS 8 BP 965 EP 973 DI 10.1007/s10552-005-4500-3 PG 9 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 957EP UT WOS:000231352700007 PM 16132805 ER PT J AU Anderson, LW Collins, JM Klecker, RW Katki, AG Parchment, RE Boinpally, RR LoRusso, PM Ivy, SP AF Anderson, LW Collins, JM Klecker, RW Katki, AG Parchment, RE Boinpally, RR LoRusso, PM Ivy, SP TI Metabolic profile of XK469 (2(R)-[4-(7-chloro-2-quinoxalinyl)oxyphenoxy]-propionic acid; NSC698215) in patients and in vitro: low potential for active or toxic metabolites or for drug-drug interactions SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE NSC698215; metabolites; drug-drug interactions ID ALDEHYDE OXIDASE ACTIVITY; HUMAN LIVER; BIOLOGICAL EVALUATION; ANTITUMOR AGENT; GUINEA-PIG; RAT-LIVER; ZALEPLON; PHARMACOKINETICS; INHIBITION; OXIDATION AB As part of an ongoing phase 1 study, we studied the excretion of XK469 and its metabolism in patients and in vitro. Five primary metabolites were identified by HPLC/MS/MS. An oxidized product formed by cytosolic aldehyde oxidase was the predominant species both in urine and human hepatocytes in vitro. Conjugates of XK469 with glycine, taurine, and glucuronic acid, as well as the microsomal product, 4-oxo-XK469, were also found in urine and in vitro, but none were major contributors to the mass balance for XK469 elimination. Based upon the relative concentrations circulating in plasma, systemic exposure to parent drug was 100-fold higher than for the metabolites. Thus, both toxicity and efficacy of XK469 are most likely to be produced by the parent molecule, rather than the metabolites. Urinary recovery of parent drug was low (2% of dose in 24 h), partly because of the long half-life of XK469 (approximately 3 days). In addition, the metabolite profile in urine indicates that only 25% of the XK469-derived material was unchanged drug. Thus, urinary excretion was not a major factor in XK469 elimination. Variations in systemic exposure to XK469 will be strongly influenced by factors that alter the activity of aldehyde oxidase, including pharmacogenetics, enzyme inhibition, and enzyme induction, but no specific modifiers have been reported. The multiday half-life of XK469 hampered our ability to obtain a complete mass balance, and the possibility exists that other routes, such as biliary excretion, may also play a substantial role in XK469 disposition. C1 US FDA, Lab Clin Pharmacol, Silver Spring, MD 20993 USA. Wayne State Univ, Karmanos Canc Ctr, Detroit, MI USA. NCI, Canc Therapy Evaluat Program, Rockville, MD USA. RP Anderson, LW (reprint author), US FDA, Lab Clin Pharmacol, WO Bldg 64,Rm 2014,10903 New Hampshire Ave,HFD-90, Silver Spring, MD 20993 USA. EM ANDERSONL@cder.fda.gov FU NCI NIH HHS [U01-CA062487] NR 24 TC 9 Z9 9 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD OCT PY 2005 VL 56 IS 4 BP 351 EP 357 DI 10.1007/s00280-004-0962-3 PG 7 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 950CK UT WOS:000230835000004 PM 15895233 ER PT J AU Hartman, TJ Yu, BB Albert, PS Slattery, ML Paskett, E Kikendall, JW Iber, F Brewer, BK Schatzkin, A Lanza, E AF Hartman, TJ Yu, BB Albert, PS Slattery, ML Paskett, E Kikendall, JW Iber, F Brewer, BK Schatzkin, A Lanza, E CA Polyp Prevention Study Grp TI Does nonsteroidal anti-inflammatory drug use modify the effect of a low-fat, high-fiber diet on recurrence of colorectal adenomas? SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID COLON-CANCER; PHYSICAL-ACTIVITY; PREVENTION; TRIAL; RISK; INTERVENTION; ACIDS AB The Polyp Prevention Trial was designed to evaluate the effects of a high-fiber (18 g/1,000 kcal), high-fruit and -vegetable (3.5 servings/1,000 kcal), low-fat (20% energy) diet on recurrence of adenomatous polyps. Participants >= 35 years of age, with histologically confirmed colorectal adenoma(s) removed in the prior 6 months, were randomized to the intervention or control group. Demographic, dietary, and clinical information, including use of nonsteroidal anti-inflammatory drugs (NSAID), was collected at baseline and four annual visits. Adenoma recurrence was found in 754 of 1,905 participants and was not significantly different between groups. NSAID use was associated with a significant reduction in recurrence [odds ratio (OR), 0.77; 95% confidence interval (95% CI), 0.63-0.95]. In this analysis, NSAIDs modified the association between the intervention and recurrence at baseline (P = 0.02) and throughout the trial (P = 0.008). Among participants who did not use NSAIDs, the intervention was in the protective direction but did not achieve statistical significance (OR, 0.87; 95% CI, 0.69-1.09). The intervention was protective among males who did not use NSAIDs at baseline (OR, 0.71; 95% CI, 0.54-0.94), but not among NSAIDs users (OR, 1.09; 95% CI, 0.74-1.62). For females, corresponding OR estimates were 1.28 (95% CI, 0.86-1.90) and 2.30 (95% CI, 1.24-4.27), respectively. The protective association observed for NSAID use was stronger among control (OR, 0.63; 95% CI, 0.47-0.84) than for intervention group participants (OR, 0.97; 95% CI, 0.74-1.28). These results should be interpreted cautiously given that they may have arisen by chance in the course of examining multiple associations and Polyp Prevention Trial study participants were not randomly assigned to both dietary intervention and NSAID use. Nevertheless, our results suggest that adopting a low-fat, high-fiber diet rich in fruits and vegetables may lower the risk of colorectal adenoma recurrence among individuals who do not regularly use NSAIDs. C1 Penn State Univ, Dept Nutr Sci, University Pk, PA 16802 USA. Informat Management Serv Inc, Rockville, MD USA. Westat Corp, Rockville, MD USA. NCI, Biometr Res Branch, Div Canc Treatment & Diagnosis, Ctr Canc Res, Bethesda, MD 20892 USA. NCI, Nutr Epidemiol Branch, Div Epidemiol & Genet, Canc Res Ctr, Bethesda, MD 20892 USA. NCI, Lab Canc Prevent, Canc Res Ctr, Bethesda, MD 20892 USA. Univ Utah, Salt Lake City, UT USA. Ohio State Univ, Columbus, OH 43210 USA. Natl Naval Med Res Inst, Washington, DC USA. Vet Affairs Edward Hines Jr Hosp, Vet Affairs Med Ctr, Hines, IL USA. RP Hartman, TJ (reprint author), Penn State Univ, Dept Nutr Sci, 5A Henderson Bldg, University Pk, PA 16802 USA. EM tjh9@psu.edu NR 19 TC 8 Z9 10 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD OCT PY 2005 VL 14 IS 10 BP 2359 EP 2365 DI 10.1158/1055-9965.EPI-05-0333 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 972SL UT WOS:000232473400013 PM 16214917 ER PT J AU Goldin, LR Landgren, O McMaster, ML Gridley, G Hemminki, K Li, XJ Mellemkjaer, L Olsen, JH Linet, MS AF Goldin, LR Landgren, O McMaster, ML Gridley, G Hemminki, K Li, XJ Mellemkjaer, L Olsen, JH Linet, MS TI Familial aggregation and heterogeneity of non-Hodgkin lymphoma in population-based samples SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; LONG-TERM SURVIVORS; CANCER DATABASE; LYMPHOPROLIFERATIVE TUMORS; CLINICAL CHARACTERISTICS; PSEUDOAUTOSOMAL LINKAGE; RISK; DISEASE; CLASSIFICATION; ANTICIPATION AB The importance of genetic factors in the etiology of non-Hodgkin lymphoma (NHL) is suggested by case-control and cohort studies. Most previous studies have been too small to estimate accurately risks of specific categories of lymphoproliferative malignancies in relatives of NHL cases or to quantify the contribution of NHL case characteristics to familial risk. We have overcome sample size limitations and potential recall bias by using large databases from Sweden and Denmark. Diagnoses of lymphoproliferative malignancies were compared in 70,006 first-degree relatives of 26,089 NHL cases (including 7,432 with subtype information) versus 161,352 first-degree relatives of 58,960 matched controls. Relatives of NHL cases were at significantly increased risk for NHL [relative risk (RR), 1.73; 95% confidence interval (95% CI), 1.39-2.15], Hodgkin lymphoma (RR, 1.41; 95% Cl, 1.0-1.97), and nonsignificantly for chronic lymphocytic leukemia (CLL; RR, 1.31; 95% CI, 0.93-1.85). No increased risk was found for multiple myeloma among case relatives. Findings with respect to siblings compared with parents and offspring or with respect to age at diagnosis of proband were inconsistent. In both populations, relatives of cases with an aggressive NHL subtype were at substantially increased risk of NHL (combined RR, 3.56; 95% CI, 1.80-7.02). We conclude that NHL has an important familial component, which is shared with Hodgkin lymphoma and CLL. We estimate that the absolute lifetime risk for a first-degree relative of an NHL case to develop NHL is 3.6% (compared with a population risk of 2.1%) and higher if the index case had an aggressive subtype of NHL. C1 NCI, Div Canc Epidemiol & Genet, Genet Epidemiol Branch, Bethesda, MD 20892 USA. NCI, Div Canc Epidemiol & Genet, Radiat Epidemiol Branch, Bethesda, MD 20892 USA. NCI, Div Canc Epidemiol & Genet, Biostat Branch, Bethesda, MD 20892 USA. German Canc Res Ctr, Div Mol Genet Epidemiol, D-6900 Heidelberg, Germany. Karolinska Inst, Dept Biosci, Novum, Stockholm, Sweden. Danish Canc Soc, Inst Canc Epidemiol, Copenhagen, Denmark. RP Goldin, LR (reprint author), NCI, Div Canc Epidemiol & Genet, Genet Epidemiol Branch, 6120 Execut Blvd,MSC 7236, Bethesda, MD 20892 USA. EM goldinl@mail.nih.gov OI Olsen, Jorgen Helge/0000-0001-9633-5662 FU Intramural NIH HHS NR 35 TC 44 Z9 45 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 2005 VL 14 IS 10 BP 2402 EP 2406 DI 10.1158/1055-9965.EPI-05-0346 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 972SL UT WOS:000232473400019 PM 16214923 ER PT J AU Il'yasova, D Colbert, LH Harris, TB Newman, AB Bauer, DC Satterfield, S Kritchevsky, SB AF Il'yasova, D Colbert, LH Harris, TB Newman, AB Bauer, DC Satterfield, S Kritchevsky, SB TI Circulating levels of inflammatory markers and cancer risk in the health aging and body composition cohort SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID C-REACTIVE PROTEIN; CORONARY-HEART-DISEASE; RENAL-CELL CARCINOMA; COLORECTAL-CANCER; LUNG-CANCER; INTERLEUKIN-6 RECEPTOR; ORGAN-TRANSPLANTATION; PROGNOSTIC-FACTORS; PANCREATIC-CANCER; ELDERLY SUBJECTS AB Background: Chronic inflammation is associated with processes that contribute to the onset or progression of cancer. This study examined the relationships between circulating levels of the inflammatory markers interleukin-6 (IL-6), Creactive protein (CRP), and tumor necrosis factor-alpha (TNF-alpha) and total as well as site-specific cancer incidence. Methods: Study subjects (n = 2,438) were older adults (ages 70-79 years) participating in the Health Aging and Body Composition study, who did not report a previous cancer diagnosis (except for nonmelanoma skin cancer) at baseline. Incident cancer events (n = 296) were ascertained during an average follow-up of 5.5 years. Inflammatory markers were measured in stored baseline fasting blood samples. Results: The adjusted hazard ratios (95% confidence intervals) for incident cancer associated with a 1-unit increase on the natural log-scale were 1.13 (0.94-1.37), 1.25 (1.09-1.43), and 1.28 (0.96-1.70) for IL-6, CRP, and TNF-a, respectively. Markers were more strongly associated with cancer death: hazard ratios were 1.63 (1.19-2.23) for IL-6, 1.64 (1.20-2.24) for CRP, and 1.82 (1.14-2.92) for TNF-alpha. Although precision was low for site-specific analyses, our results suggest that all three markers were associated with lung cancer, that IL-6 and CRP were associated with colorectal cancer, and that CRP was associated with breast cancer. Prostate cancer was not associated with any of these markers. Conclusions: These findings suggest that (a) the associations between IL-6, CRP, and TNF-a and the risk of cancer may be site specific and (b) increased levels of inflammatory markers are more strongly associated with the risk of cancer death than cancer incidence. C1 Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. Univ Wisconsin, Madison, WI USA. NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, Bethesda, MD 20892 USA. Univ Pittsburgh, Pittsburgh, PA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Tennessee, Memphis, TN 38163 USA. RP Il'yasova, D (reprint author), Duke Univ, Med Ctr, Canc Prevent Detect & Control Res Program, Box 2949, Durham, NC 27710 USA. EM dora.ilyasova@duke.edu RI Newman, Anne/C-6408-2013; OI Newman, Anne/0000-0002-0106-1150; Kritchevsky, Stephen/0000-0003-3336-6781 FU NIA NIH HHS [N01-AG-6-2103, N01-AG-6-2106, P30-AG-021332-02, N01-AG-6-2101] NR 48 TC 238 Z9 240 U1 1 U2 9 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 2005 VL 14 IS 10 BP 2413 EP 2418 DI 10.1158/1055-9965.EPI-05-0316 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 972SL UT WOS:000232473400021 PM 16214925 ER PT J AU Bhatti, P Sigurdson, AJ Wang, SS Chen, JB Rothman, N Hartge, P Bergen, AW Landi, MT AF Bhatti, P Sigurdson, AJ Wang, SS Chen, JB Rothman, N Hartge, P Bergen, AW Landi, MT TI Genetic variation and willingness to participate in epidemiologic research: Data from three studies SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID POSTAL HEALTH SURVEY; POPULATION STRATIFICATION; RESPONDENTS; CANCER; BIAS; QUESTIONNAIRE; NONRESPONDENTS; VARIANTS AB The differences in common genetic polymorphism frequencies by willingness to participate in epidemiologic studies are unexplored, but the same threats to internal validity operate as for studies with nongenetic information. We analyzed single nucleotide polymorphism genotypes, haplotypes, and short tandem repeats among control groups from three studies with different recruitment designs that included early, late, and never questionnaire responders, one or more participation incentives, and blood or buccal DNA collection. Among 2,955 individuals, we compared 108 genotypes, 8 haplotypes, and 9 to 15 short tandem repeats by respondent type. Among our main comparisons, single nucleotide polymorphism genotype frequencies differed significantly (P < 0.05) between respondent groups in six instances, with 13 expected by chance alone. When comparing the odds of carrying a variant among the various response groups, 19 odds ratios were <= 0.70 or <= 1.40, levels that might be notably different. Among the various respondent group comparisons, haplotype and short tandem repeat frequencies were not significantly different by willingness to participate. We observed little evidence to suggest that genotype differences underlie response characteristics in molecular epidemiologic studies, but a greater variety of genes should be examined, including those related to behavioral traits potentially associated with willingness to participate. To the extent possible, investigators should evaluate their own genetic data for bias in response categories. C1 NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Bhatti, P (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, 6120 Execut Blvd,EPS 7091,MSC 7238, Bethesda, MD 20892 USA. EM bhattip@mail.nih.gov OI Bergen, Andrew/0000-0002-1237-7644 NR 22 TC 61 Z9 61 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 2005 VL 14 IS 10 BP 2449 EP 2453 DI 10.1158/1055-9965.EPI-05-0463 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 972SL UT WOS:000232473400027 PM 16214931 ER PT J AU Peek, RM Mohla, S DuBois, RN AF Peek, RM Mohla, S DuBois, RN TI Inflammation in the genesis and perpetuation of cancer: Summary and recommendations from a national cancer institute-sponsored meeting SO CANCER RESEARCH LA English DT Article ID PATHOGENESIS; METASTASIS AB The Inflammation and Cancer Think Tank Meeting was organized by the National Cancer Institute with the purpose of identifying research advances, gaps, and opportunities for the study and clinical application of the role of inflammation on tumorigenesis. The format of this meeting consisted of brief presentations that focused on concepts, with extensive discussion periods to allow participants to identify issues and barriers limiting progress in this area. The strong relationship between inflammation and cancer in the gastrointestinal tract prompted several presentations that were focused on carcinogenesis within this organ system; however, many of the same immune mediators that influence esophageal, gastric, and colorectal carcinoma were also shown to influence inflammation-related malignancies at other anatomic sites. This article summarizes the findings of this Think Tank Meeting, which highlight the intimate relationship between malignant cells and their inflammatory microenvironment and specifically address opportunities to manipulate the host immune response and therefore intervene at different points along the tumorigenic cascade. C1 Vanderbilt Univ, Sch Med, Div Gastroenterol, Dept Med, Nashville, TN 37232 USA. Vanderbilt Univ, Sch Med, Div Gastroenterol, Dept Canc Biol, Nashville, TN 37232 USA. Med Ctr Nashville, Dept Vet Affairs, Nashville, TN USA. NCI, Tumor Biol & Metastasis Branch, Div Canc Biol, NIH, Bethesda, MD 20892 USA. RP Peek, RM (reprint author), Vanderbilt Univ, Sch Med, Div Gastroenterol, Dept Med, 1161 21st Ave S,C-2104 Med Ctr N, Nashville, TN 37232 USA. EM richard.peek@vanderbilt.edu NR 16 TC 45 Z9 46 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 1 PY 2005 VL 65 IS 19 BP 8583 EP 8586 DI 10.1158/0008-5472.CAN-05-1777 PG 4 WC Oncology SC Oncology GA 968YL UT WOS:000232199400003 PM 16204020 ER PT J AU Bowen, TJ Yakushiji, H Montagna, C Jain, S Ried, T Wynshaw-Boris, A AF Bowen, TJ Yakushiji, H Montagna, C Jain, S Ried, T Wynshaw-Boris, A TI Atm heterozygosity cooperates with loss of Brca1 to increase the severity of mammary gland cancer and reduce ductal branching SO CANCER RESEARCH LA English DT Article ID ATAXIA-TELANGIECTASIA HETEROZYGOTES; SPORADIC BREAST-CANCER; DNA-DAMAGE RESPONSE; FAMILIAL BREAST; CENTROSOME AMPLIFICATION; GENETIC INSTABILITY; MISSENSE MUTATIONS; EPITHELIAL-CELLS; DEFICIENT MICE; OVARIAN-CANCER AB The role of homozygous ataxia telangiectasia mutated (ATM) mutations in familial and sporadic forms of cancer is well established, but the contribution of ATM heterozygosity to mammary gland and other cancers has been controversial. To test the effect of Atm heterozygosity on mammary gland cancer, mice with complete loss of exon 11 of Brca-1 specifically in mammary epithelium (Brea1-MG-Delta ex11) were studied in either Atm heterozygous or Atm wild-type backgrounds. Targeted deletion of Brcal in mammary epithelium resulted in carcinomas and adenocarcinomas of varying histology with long (> 9 months) latency. Latency to tumorigenesis was found to be unchanged in the Brca1-MG Delta ex11;Atm heterozygous mice compared with Brca1-MG Delta exll;Atm wild-type mice. However, the mice displayed variable tumor severity and differences in mammary tissue development. Mammary tumors from Brea1-MG-Delta ex11;-4tm heterozygous mice were anaplastic and undifferentiated in all 20 tumors tested, whereas tumors from mice that were Brea1-MG-Delta ex11 but wild-type for Atm displayed variable histologic profiles, with some anaplastic tumors and other differentiated and less invasive tumor types. Previously reported developmental defects for Brea1-deficient mice were also observed in our model with and without Atm heterozygosity, but Brea1-MG-Delta ex11 Atm heterozygous mice displayed decreased ductal branching during puberty, a phenotype that was not observed in Brea1-MG-Delta ex11; Atm wild-type mice. Our results provide evidence that Atm heterozygosity influences severity of mammary gland tumors in the Brca1-MG-Delta ex11 tumor-prone mouse and suggest that this mutation leads to a newly characterized developmental defect during glandular maturation. C1 Univ Calif San Diego, Sch Med, Dept Pediat Med, Med Teaching Facil, La Jolla, CA 92093 USA. Univ Calif San Diego, Ctr Comprehens Canc, La Jolla, CA 92093 USA. Univ Calif San Diego, Div Biostat & Bioinformat, La Jolla, CA 92093 USA. Univ Calif San Diego, Dept Family & Prevent Med, La Jolla, CA 92093 USA. NCI, Genet Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Wynshaw-Boris, A (reprint author), Univ Calif San Diego, Sch Med, Dept Pediat Med, Med Teaching Facil, 9500 Gilman Dr,Rom 253,MC 0627, La Jolla, CA 92093 USA. EM awynshawboris@ucsd.edu NR 53 TC 11 Z9 11 U1 0 U2 1 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 2005 VL 65 IS 19 BP 8736 EP 8746 DI 10.1158/0008-5472 PG 11 WC Oncology SC Oncology GA 968YL UT WOS:000232199400025 PM 16204043 ER PT J AU Shen, KC Heng, H Wang, YL Lu, S Liu, G Deng, CX Brooks, SC Wang, YA AF Shen, KC Heng, H Wang, YL Lu, S Liu, G Deng, CX Brooks, SC Wang, YA TI ATM and p21 cooperate to suppress aneuploidy and subsequent tumor development SO CANCER RESEARCH LA English DT Article ID CELL-CYCLE CHECKPOINT; LI-FRAUMENI-SYNDROME; SACCHAROMYCES-CEREVISIAE; TARGETED INACTIVATION; TELOMERE DYSFUNCTION; GENOME STABILITY; DEFICIENT MICE; MOUSE MODELS; DNA-REPAIR; P53 AB The DNA damage checkpoint protein kinase mutated in ataxia telangiectasia (ATM) is involved in sensing and transducing DNA damage signals by phosphorylating and activating downstream target proteins that are implicated in the regulation of cell cycle progression and DNA repair. Atm(-/-)cells are defective in cellular proliferation mediated by the Arf/p53/p21 pathway. In this report, we show that increase expression of p21 (also known as Waft or CDKN1a) in Atm(-/-)cells serves as a cellular defense mechanism to suppress further chromosomal instability (CIN) and tumor development because Atm(-/-)p21(-/-) mice are predisposed to carcinomas and sarcomas with intratumoral heterogeneity. It was found that Atm-deficient cells are defective in metaphase-anaphase transition leading to abnormal karyokinesis. Moreover, Atm(-/-)p21(-/-) primary embryonic fibroblasts exhibit increased CIN compared with either Atm(-/-) or p21(-/-) cells. The increased CIN is manifested at the cellular level by increased chromatid breaks and elevated aneuploid genome in Atm(-/-)p21(-/-) cells. Finally, we showed that the role of p21 in a CIN background induced by loss of Atm is to suppress numerical CIN but not structural CIN. Our data suggest that the development of aneuploidy precedes tumor formation a implicates p21 as a major tumor suppressor in a genome instability background. C1 Wayne State Univ, Barbara Ann Karmanos Canc Inst, Sch Med, Detroit, MI 48201 USA. Wayne State Univ, Ctr Mol Med, Sch Med, Detroit, MI 48201 USA. Wayne State Univ, Dept Biochem & Mol Biol, Sch Med, Detroit, MI 48201 USA. Schering Plough Res Inst, Dept Tumor Biol, Kenilworth, NJ USA. Natl Inst Digest & Kidney Dis, Genet & Dev & Dis Branch, NIH, Bethesda, MD USA. RP Wang, YA (reprint author), Wayne State Univ, Barbara Ann Karmanos Canc Inst, Sch Med, 110 E Warren Ave, Detroit, MI 48201 USA. EM wangya@karmanos.org RI deng, chuxia/N-6713-2016 FU NCI NIH HHS [R01CA89526]; NIEHS NIH HHS [P30 ES06639] NR 56 TC 47 Z9 48 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 1 PY 2005 VL 65 IS 19 BP 8747 EP 8753 DI 10.1158/0008-5472 PG 7 WC Oncology SC Oncology GA 968YL UT WOS:000232199400026 PM 16204044 ER PT J AU Kong, DH Park, EJ Stephen, AG Calvani, M Cardellina, JH Monks, A Fisher, RJ Shoemaker, RH Melillo, G AF Kong, DH Park, EJ Stephen, AG Calvani, M Cardellina, JH Monks, A Fisher, RJ Shoemaker, RH Melillo, G TI Echinomycin, a small-molecule inhibitor of hypoxia-inducible factor-1 DNA-binding activity SO CANCER RESEARCH LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; PROSTATE-CANCER CELLS; FACTOR 1-ALPHA; FACTOR-1-ALPHA PROTEIN; TRANSCRIPTION FACTORS; TUMOR ANGIOGENESIS; FACTOR EXPRESSION; ONCOLOGY-GROUP; PATHWAY; HIF-1-ALPHA AB The identification of small molecules that inhibit the sequence-specific binding of transcription factors to DNA is an attractive approach for regulation of gene expression. Hypoxia-inducible factor-1 (HIF-1) is a transcription factor that controls genes involved in glycolysis, angiogenesis, migration, and invasion, all of which are important for tumor progression and metastasis. To identify inhibitors of HIF-1 DNA-binding activity, we expressed truncated HIF-1 alpha and HILF-1 beta proteins containing the basic-helix-loop-helix and PAS domains. Expressed recombinant HIF-1 alpha and HILF-1 beta proteins induced a specific DNA-binding activity to a double-stranded oligonucleotide containing a canonical hypoxia-responsive element (HRE). One hundred twenty-eight compounds previously identified in a HIF-1-targeted cell-based high-throughput screen of the National Cancer Institute 140,000 small-molecule library were tested in a 96-well plate ELISA for inhibition of HEF-1 DNA-binding activity. One of the most potent compounds identified, echinomycin (NSC-13502), a small-molecule known to bind DNA in a sequence-specific fashion, was further investigated. Electrophoretic mobility shift assay experiments showed that NSC-13502 inhibited binding of HIF-1 alpha and HIF-10 proteins to a HRE sequence but not binding of the corresponding proteins to activator protein-1 (AP-1) or nuclear factor-kappa B (NF-kappa B) consensus sequences. Interestingly, chromatin immunoprecipitation experiments showed that NSC-13502 specifically inhibited binding of HIF-1 to the HRE sequence contained in the vascular endothelial growth factor (VEGF) promoter but not binding of AP-1 or NF-kappa B to promoter regions of corresponding target genes. Accordingly, NSC-13502 inhibited hypoxic induction of luciferase in U251-HRE cells and VEGF mRNA expression in U251 cells. Our results indicate that it is possible to identify small molecules that inhibit HIF-1 DNA binding to endogenous promoters. C1 NCI, Dev Therapeut Program, Tumor Hypoxia Lab, Screening Technol Branch, Frederick, MD 21702 USA. Sci Applicat Int Corp, Frederick, MD USA. RP Melillo, G (reprint author), NCI, Dev Therapeut Program, Tumor Hypoxia Lab, Screening Technol Branch, Bldg 432,Room 218, Frederick, MD 21702 USA. EM melillog@ncifcrf.gov RI Fisher, Robert/B-1431-2009 FU NCI NIH HHS [N01-CO-12400] NR 50 TC 244 Z9 252 U1 1 U2 22 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 2005 VL 65 IS 19 BP 9047 EP 9055 DI 10.1158/0008-5472.CAN-05-1235 PG 9 WC Oncology SC Oncology GA 968YL UT WOS:000232199400061 PM 16204079 ER PT J AU Lee, KS Asano, S Park, JE Sakchaisri, K Erikson, RL AF Lee, KS Asano, S Park, JE Sakchaisri, K Erikson, RL TI Monitoring the cell cycle by multi-kinase-dependent regulation of Swe1/Wee1 in budding yeast SO CELL CYCLE LA English DT Article DE Swe1; Cla4; Cdc5; Cdc28; G2/M transition; budding yeast ID NIM1/CDR1 MITOTIC INDUCER; SACCHAROMYCES-CEREVISIAE; PROTEIN-KINASE; SWE1P DEGRADATION; MORPHOGENESIS CHECKPOINT; NEGATIVE REGULATION; WEE1; PHOSPHORYLATION; INACTIVATION; CYTOKINESIS AB In eukaryotes, G(2)/M transition is induced by the activation of cyclin B-bound Cdk1, which is held in check by the protein kinase, Wee1. Recent advances in our understanding of mitotic entry in budding yeast has revealed that these cells utilize the level of Swe1 ( Wee1 ortholog) phosphorylation as a means of monitoring cell cycle progression and of coordinating morphogenetic events with mitotic entry. Swe1 is phosphorylated by at least three distinct kinases at different stages of the cell cycle. This cumulative phosphorylation leads to the hyperphosphorylation and degradation of Swe1 through ubiquitin-mediated proteolysis. Thus, Swe1 functions as an important cell cycle modulator that integrates multiple upstream signals from prior cell cycle events before its ultimate degradation permits passage into mitosis. C1 NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Harvard Univ, Biol Labs, Cambridge, MA 02138 USA. RP Lee, KS (reprint author), NCI, Lab Metab, Ctr Canc Res, NIH, 9000 Rockville Pike,Bldg 37,Rm 3118, Bethesda, MD 20892 USA. EM kyunglee@mail.nih.gov NR 33 TC 14 Z9 14 U1 0 U2 0 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD OCT PY 2005 VL 4 IS 10 BP 1346 EP 1349 DI 10.4161/cc.4.10.2049 PG 4 WC Cell Biology SC Cell Biology GA 990NW UT WOS:000233751500011 PM 16123596 ER PT J AU Jirmanova, L Bulavin, DV Fornace, AJ AF Jirmanova, L Bulavin, DV Fornace, AJ TI Inhibition of the ATR/Chk1 pathway induces a p38-dependent S-phase delay in mouse embryonic stem cells SO CELL CYCLE LA English DT Article DE ATM; ATR; embryonic stem cells; caffeine; cell cycle; p38 alpha ID DNA-DAMAGE CHECKPOINT; ACTIVATED PROTEIN-KINASE; CYCLE CHECKPOINT; ATAXIA-TELANGIECTASIA; TARGETED DISRUPTION; CHROMOSOMAL FRAGMENTATION; IONIZING-RADIATION; ATR; CAFFEINE; APOPTOSIS AB Ataxia-telangiectasia mutated (ATM) and ATM- and Rad3-related (ATR) kinases, family members of the PI-3 kinase related proteins, play a key role in checkpoint activation and maintenance of genomic stability following DNA damage. We have used wild type (WT) and p38 alpha-deficient mouse embryonic stem (ES) cells to investigate the role of ATR and ATM kinases during embryonic cell cycle. We have found that inhibition of ATR and ATM kinases with caffeine or Chk1 with UCN-01, results in activation of a p38-dependent intra-S-phase checkpoint and activation of apoptosis in ES cells. However, wortmannin at a concentration, that inhibits ATM kinase but not ATR kinase, did not affect cell cycle progression. Furthermore, the presence of caffeine results in activation of p38 kinase, accumulation of p21/Waf1 in a complex with Cdk2 and decrease of Cdk2 kinase activity. In contrast, caffeine-treated p38 alpha(-/-) ES cells show less apoptosis, and fail to trigger an effective S-phase checkpoint and accumulation of p21/Waf1. We conclude that ATR kinase activity is essential for normal cell cycle progression of exponentially proliferating mouse ES cells even in the absence of exogenous DNA damage, and ATR deregulation triggers p38 alpha-dependent cell-cycle checkpoint and apoptotic responses. C1 Harvard Univ, Sch Publ Hlth, Dept Genet & Complex Dis, Boston, MA 02115 USA. NCI, Lab Immune Cell Biol, Bethesda, MD 20892 USA. Inst Mol & Cell Biol, Proteos, Singapore. RP Fornace, AJ (reprint author), Harvard Univ, Sch Publ Hlth, Dept Genet & Complex Dis, Room 121,665 Huntington Ave, Boston, MA 02115 USA. EM afornace@hsph.harvard.edu RI Fornace, Albert/A-7407-2008; ASTAR, IMCB/E-2320-2012 OI Fornace, Albert/0000-0001-9695-085X; FU Intramural NIH HHS NR 67 TC 22 Z9 22 U1 0 U2 0 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD OCT PY 2005 VL 4 IS 10 BP 1428 EP 1434 DI 10.4161/cc.4.10.2055 PG 7 WC Cell Biology SC Cell Biology GA 990NW UT WOS:000233751500027 PM 16138010 ER PT J AU Abella, A Dubus, P Malumbres, M Rane, SG Kiyokawa, H Sicard, A Vignon, F Langin, D Barbacid, M Fajas, L AF Abella, A Dubus, P Malumbres, M Rane, SG Kiyokawa, H Sicard, A Vignon, F Langin, D Barbacid, M Fajas, L TI Cdk4 promotes adipogenesis through PPAR gamma activation SO CELL METABOLISM LA English DT Article ID ADIPOCYTE DIFFERENTIATION; CELL-CYCLE; RETINOBLASTOMA PROTEIN; HISTONE DEACETYLASE; RECEPTOR-GAMMA; IN-VIVO; EXPRESSION; PHOSPHORYLATION; BINDING; PROLIFERATION AB Cell cycle regulators such as E2F1 and retinoblastoma (RB) play crucial roles in the control of adipogenesis, mostly by controlling the transition between preadipocyte proliferation and adipocyte differentiation. The serine-threonine kinase cyclin-dependent kinase 4 (cdk4) works in a complex with D-type cyclins to phosphorylate RB, mediating the entry of cells into the cell cycle in response to external stimuli. Because cdk4 is an upstream regulator of the E2F-RB pathway, we tested whether cdk4 was a target for new factors that regulate adipogenesis. Here we find that cdk4 inhibition impairs adipocyte differentiation and function. Disruption of cdk4 or activating mutations in cdk4 in primary mouse embryonic fibroblasts results in reduced and increased adipogenic potential, respectively, of these cells. We show that the effects of cdk4 are not limited to the control of differentiation; cdk4 also participates in adipocyte function through activation of PPAR gamma. C1 INSERM, U540, Equipe Avenir, F-34090 Montpellier, France. Univ Victor Segalen, F-33076 Bordeaux, France. Ctr Nacl Invest Oncol Carlos 3, E-28220 Madrid, Spain. NCI, Lab Cell Regulat & Carcinogenesis, Cell Cycle & Human Dis Grp, NIH, Bethesda, MD 20892 USA. INSERM, U586, F-31059 Toulouse, France. Univ Illinois, Coll Med, Dept Biochem & Mol Genet, Chicago, IL 60607 USA. Univ Montpellier, Hop Arnaud Villeneuve, Ctr Hosp, F-34295 Montpellier, France. RP Fajas, L (reprint author), INSERM, U540, Equipe Avenir, F-34090 Montpellier, France. EM fajas@montp.inserm.fr RI Malumbres, Marcos/E-8834-2011; OI Malumbres, Marcos/0000-0002-0829-6315; Langin, Dominique/0000-0002-2669-7825 NR 39 TC 77 Z9 81 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1550-4131 J9 CELL METAB JI Cell Metab. PD OCT PY 2005 VL 2 IS 4 BP 239 EP 249 DI 10.1016/j.cmet.2005.09.003 PG 11 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 974TB UT WOS:000232613200006 PM 16213226 ER PT J AU Nofer, JR Remaley, AT AF Nofer, JR Remaley, AT TI Tangier disease: still more questions than answers SO CELLULAR AND MOLECULAR LIFE SCIENCES LA English DT Review DE Tangier disease; high-density lipoprotein (HDL); arteriosclerosis; reverse cholesterol transport; cholesterol efflux; ATP-binding cassette transporter 1 (ABCA1) ID HIGH-DENSITY-LIPOPROTEIN; APOLIPOPROTEIN-A-I; CASSETTE TRANSPORTER A1; CELLULAR CHOLESTEROL EFFLUX; CORONARY HEART-DISEASE; HUMAN-SKIN FIBROBLASTS; SMOOTH-MUSCLE-CELLS; LIPID EFFLUX; APOA-I; TRANSGENIC MICE AB High-density lipoproteins (HDLs) play a central role in transporting cholesterol from peripheral tissues to the liver for elimination from the body. Impairment of HDL-mediated cholesterol transport favors cholesterol deposition in the arterial wall and promotes development of arteriosclerosis. Tangier disease is a severe HDL deficiency syndrome characterized by the accumulation of cholesterol in tissue macrophages and prevalent atherosclerosis. A three-decade search for a culprit in Tangier disease led to the identification of mutations in a cell membrane protein called ABCA1, which mediates the secretion of excess cholesterol from cells into the HDL metabolic pathway. Because of its ability to deplete cells of cholesterol and to raise plasma HDL levels, ABCA1 has become a promising therapeutic target for preventing cardiovascular disease. C1 Univ Munster, Inst Klin Chem & Lab Med, D-48129 Munster, Germany. Univ Munster, Inst Arterioskleroseforsch, D-48129 Munster, Germany. NIH, Dept Lab Med, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Nofer, JR (reprint author), Univ Munster, Inst Klin Chem & Lab Med, Albert Schweitzer Str 33, D-48129 Munster, Germany. EM nofer@uni-muenster.de NR 105 TC 48 Z9 50 U1 0 U2 3 PU BIRKHAUSER VERLAG AG PI BASEL PA VIADUKSTRASSE 40-44, PO BOX 133, CH-4010 BASEL, SWITZERLAND SN 1420-682X J9 CELL MOL LIFE SCI JI Cell. Mol. Life Sci. PD OCT PY 2005 VL 62 IS 19-20 BP 2150 EP 2160 DI 10.1007/s00018-005-5125-0 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 975XG UT WOS:000232696800002 PM 16235041 ER PT J AU Che, MM Boja, ES Yoon, HY Gruschus, J Jaffe, H Stauffer, S Schuck, P Fales, HM Randazzo, PA AF Che, MM Boja, ES Yoon, HY Gruschus, J Jaffe, H Stauffer, S Schuck, P Fales, HM Randazzo, PA TI Regulation of ASAP1 by phospholipids is dependent on the interface between the PH and Arf GAP domains SO CELLULAR SIGNALLING LA English DT Article DE ADP-ribosylation factor; PH domains; GTPase-activating proteins ID ADP-RIBOSYLATION FACTOR; PLECKSTRIN HOMOLOGY DOMAIN; GTPASE-ACTIVATING PROTEIN; RHO-FAMILY GTPASES; PHOSPHOINOSITIDE 3-KINASES; SIGNAL-TRANSDUCTION; CRYSTAL-STRUCTURE; BINDING DOMAINS; CENTER STAGE; KINASE B AB ASAP1 is an Arf GAP with a PH domain immediately N-terminal to the catalytic Arf GAP domain. PH domains are thought to regulate enzymes by binding to specific phosphomositide lipids in membranes, thereby recruiting the enzyme to a site of action. Here, we have examined the functional relationship between the PH and Arf GAP domains. We found that GAP activity requires the cognate PH domain of ASAP1, leading us to hypothesize that the Arf GAP and PH domains directly interact to form the substrate binding site. This hypothesis was supported by the combined results of protection and hydrodynamic studies. We then examined the role of the PH domain in the regulation of Arf GAP activity. The results of saturation kinetics, limited proteolysis, FRET and fluorescence spectrometry support a model in which regulation of the GAP activity of ASAP I involves a conformational change coincident with recruitment to a membrane surface, and a second conformational change following the specific binding of phosphatidylinositol 4,5-bisphosphate. (c) 2005 Elsevier Inc. All rights reserved. C1 NCI, Cellular Oncol Lab, Canc Res Ctr, Bethesda, MD 20892 USA. NHLBI, Biophys Chem Lab, Bethesda, MD 20892 USA. NINDS, Prot Peptide Sequencing Facil, Neurochem Lab, Bethesda, MD 20892 USA. NIH, Prot Interact Resource, Div Bioengn & Phys Sci, Off Director, Bethesda, MD 20892 USA. RP Randazzo, PA (reprint author), NCI, Cellular Oncol Lab, Canc Res Ctr, Bethesda, MD 20892 USA. EM randazzo@helix.nih.gov OI Schuck, Peter/0000-0002-8859-6966 NR 60 TC 25 Z9 25 U1 0 U2 11 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 2005 VL 17 IS 10 BP 1276 EP 1288 DI 10.1016/j.cellsig.2005.01.007 PG 13 WC Cell Biology SC Cell Biology GA 954VJ UT WOS:000231182900011 PM 16038802 ER PT J AU Scher, AI Terwindt, GM Verschuren, MWMM Kruit, MC Blom, HJ Kowa, H van den Maagdenberg, AMJM van Buchem, M Ferrari, MD Launer, LJ AF Scher, AI Terwindt, GM Verschuren, MWMM Kruit, MC Blom, HJ Kowa, H van den Maagdenberg, AMJM van Buchem, M Ferrari, MD Launer, LJ TI The association of migraine with aura with the methylenetetrahydrofolate reductase (MTHFR) C677T variant and the homocysteine metabolic pathway in the general population SO CEPHALALGIA LA English DT Meeting Abstract CT 22nd Congress of the International-Headache-Society CY OCT 09-12, 2005 CL Kyoto, JAPAN SP Int Headache Soc DE migraine; aura; MTHFR; homocysteine; folate C1 Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biometr, Bethesda, MD 20814 USA. NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA. Leiden Univ, Med Ctr, Dept Neurol, Leiden, Netherlands. Natl Inst Publ Hlth & Environm, Ctr Prevent & Hlth Serv Res, NL-3720 BA Bilthoven, Netherlands. Radboud Univ Nijmegen Med Ctr, Dept Paediat, Nijmegen, Netherlands. Tottori Univ, Fac Med, Inst Neurol Sci, Dept Neurol, Yonago, Tottori 683, Japan. Leiden Univ, Med Ctr, Dept Human Genet, Leiden, Netherlands. Leiden Univ, Med Ctr, Dept Radiol, Leiden, Netherlands. RI Kruit, Mark/K-2431-2012 OI Kruit, Mark/0000-0002-4319-834X NR 0 TC 1 Z9 1 U1 1 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0333-1024 J9 CEPHALALGIA JI Cephalalgia PD OCT PY 2005 VL 25 IS 10 BP 851 EP 851 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 964TD UT WOS:000231902500042 ER PT J AU Simmons, WK Martin, A Barsalou, LW AF Simmons, WK Martin, A Barsalou, LW TI Pictures of appetizing foods activate gustatory cortices for taste and reward SO CEREBRAL CORTEX LA English DT Article DE concepts; fMRI; insula/operculum; knowledge; orbitofrontal cortex ID HUMAN ORBITOFRONTAL CORTEX; PERCEPTUAL SYMBOL SYSTEMS; HUMAN BRAIN; TEMPORAL CORTEX; SEMANTIC MEMORY; MACAQUE MONKEY; REPRESENTATION; OBJECTS; PLEASANTNESS; RECOGNITION AB Increasing research indicates that concepts are represented as distributed circuits of property information across the brain's modality-specific areas. The current study examines the distributed representation of an important but under-explored category, foods. Participants viewed pictures of appetizing foods (along with pictures of locations for comparison) during event-related fMRI. Compared to location pictures, food pictures activated the right insula/operculum and the left orbitofrontal cortex, both gustatory processing areas. Food pictures also activated regions of visual cortex that represent object shape. Together these areas contribute to a distributed neural circuit that represents food knowledge. Not only does this circuit become active during the tasting of actual foods, it also becomes active while viewing food pictures. Via the process of pattern completion, food pictures activate gustatory regions of the circuit to produce conceptual inferences about taste. Consistent with theories that ground knowledge in the modalities, these inferences arise as reenactments of modality-specific processing. C1 Emory Univ, Dept Psychol, Atlanta, GA 30322 USA. NIMH, Cognit Neuropsychol Sect, Lab Brain & Cognit, Bethesda, MD 20892 USA. RP Barsalou, LW (reprint author), Emory Univ, Dept Psychol, 532 N Kilgo Circle, Atlanta, GA 30322 USA. EM barsalou@emory.ed RI martin, alex/B-6176-2009; Simmons, William/K-8925-2015 OI Simmons, William/0000-0002-0399-9003 FU NIMH NIH HHS [1F31MH070152-01] NR 43 TC 229 Z9 231 U1 4 U2 21 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 2005 VL 15 IS 10 BP 1602 EP 1608 DI 10.1093/cercor/bhi038 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 965AH UT WOS:000231921600012 PM 15703257 ER PT J AU Bennion, BJ Cosman, M Lightstone, FC Knize, MG Montgomery, JL Bennett, LM Felton, JS Kulp, KS AF Bennion, BJ Cosman, M Lightstone, FC Knize, MG Montgomery, JL Bennett, LM Felton, JS Kulp, KS TI PhIP carcinogenicity in breast cancer: Computational and experimental evidence for competitive interactions with human estrogen receptor SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID LIGAND-BINDING DOMAIN; MAMMARY-GLAND CARCINOGENESIS; HETEROCYCLIC AMINE CONTENT; IN-VITRO ASSAYS; ER-ALPHA; CELL-PROLIFERATION; CRYSTAL-STRUCTURE; COOKED FOOD; E-SCREEN; BETA AB Many carcinogens have been shown to cause tissue specific tumors in animal models. The mechanism for this specificity has not been fully elucidated and is usually attributed to differences in organ metabolism. For heterocyclic amines, potent carcinogens that are formed in well-done meat, the ability to either bind to the estrogen receptor and activate or inhibit an estrogenic response will have a major impact on carcinogenicity. Here, we describe our work with the human estrogen receptor alpha (ER alpha), the mutagenic/carcinogenic heterocyclic amines PhIP, MeIQx, and IFP, and the hydroxylated metabolite of PhIP, N-2-hydroxy-PhIP. We demonstrate both by computational docking and NMR analysis that PhIP binds with the ligand binding domain (LBD). This binding competes with estradiol (E2) in the native E2 binding cavity of the receptor. In vitro assays show that PhIP, in contrast to the other heterocyclic amines, increases cell proliferation in MCF-7 human breast cancer cells and activates the ER alpha receptor. We also find that other heterocyclic amines and N2-hydroxy-PhIP inhibit ER alpha activation. We propose that the mechanism for the tissue-specific carcinogenicity seen in the rat breast tumors and the presumptive human breast cancer associated with the consumption of well-done meat maybe mediated by this receptor activation. C1 Lawrence Livermore Natl Lab, Biosci Directorate, Livermore, CA 94551 USA. NCI, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Kulp, KS (reprint author), Lawrence Livermore Natl Lab, Biosci Directorate, 7000 E Ave,Mail Code L-452, Livermore, CA 94551 USA. EM Kulp2@llnl.gov FU NCI NIH HHS [CA55861] NR 58 TC 23 Z9 23 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD OCT PY 2005 VL 18 IS 10 BP 1528 EP 1536 DI 10.1021/tx0501031 PG 9 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 976NM UT WOS:000232740300006 PM 16533016 ER PT J AU Swedo, SE Pine, DS AF Swedo, SE Pine, DS TI Anxiety - Preface SO CHILD AND ADOLESCENT PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Editorial Material C1 NIMH, Behav Pediat Sect, Pediat & Dev Neuropsychiat Branch, Bethesda, MD 20892 USA. NIMH, Mood & Anxiety Disorders Program, Sect Dev & Psychopathol, Bethesda, MD 20892 USA. RP Swedo, SE (reprint author), NIMH, Behav Pediat Sect, Pediat & Dev Neuropsychiat Branch, 10 Ctr Dr MSC 1255,Bldg 10,Room 4N208, Bethesda, MD 20892 USA. EM swedos@irp.nimh.nih.gov; pined@mail.nih.gov NR 0 TC 1 Z9 1 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1056-4993 J9 CHILD ADOL PSYCH CL JI Child Adolesc. Psychiatr. N. Am. PD OCT PY 2005 VL 14 IS 4 BP XV EP XVIII DI 10.1016/j.chc.2005.07.001 PG 4 WC Psychiatry SC Psychiatry GA 974BL UT WOS:000232566200002 ER PT J AU Merikangas, KR AF Merikangas, KR TI Vulnerability factors for anxiety disorders in children and adolescents SO CHILD AND ADOLESCENT PSYCHIATRIC CLINICS OF NORTH AMERICA LA English DT Review ID DSM-III-R; OBSESSIVE-COMPULSIVE DISORDER; NATIONAL COMORBIDITY SURVEY; MAJOR DEPRESSIVE DISORDER; FEAR-POTENTIATED STARTLE; DIRECT-INTERVIEW FAMILY; STRESSFUL LIFE EVENTS; POPULATION-BASED TWIN; PANIC DISORDER; BEHAVIORAL-INHIBITION AB With the maturation of community studies of adults in the past decade, there has been growing awareness of the importance of the magnitude and impact of anxiety disorders in the general population. The convergence of findings from adult and child epidemiology reveals that the onset of anxiety disorders occurs in childhood, and a substantial proportion of youth with anxiety continues to manifest lifelong problems with anxiety and other mental disorders. In this article, the major risk factors for the development of anxiety disorders in childhood and adolescence are reviewed. C1 NIMH, Bethesda, MD 20892 USA. RP Merikangas, KR (reprint author), NIMH, 35 Convent Dr,MSC 3720, Bethesda, MD 20892 USA. EM merikank@mail.nih.gov NR 185 TC 21 Z9 22 U1 6 U2 16 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1056-4993 J9 CHILD ADOL PSYCH CL JI Child Adolesc. Psychiatr. N. Am. PD OCT PY 2005 VL 14 IS 4 BP 649 EP + DI 10.1016/j.chc.2005.06.005 PG 32 WC Psychiatry SC Psychiatry GA 974BL UT WOS:000232566200004 PM 16171697 ER PT J AU Moaddel, R Patel, S Jozwiak, K Yamaguchi, R Ho, PC Wainer, IW AF Moaddel, R Patel, S Jozwiak, K Yamaguchi, R Ho, PC Wainer, IW TI Enantioselective binding to the human organic cation transporter-1 (hOCT1) determined using an immobilized hOCT1 liquid chromatographic stationary phase SO CHIRALITY LA English DT Article DE affinity chromatography; drug transporters; pharmacophore modeling; immobilized cellular membranes ID PROTEIN-COUPLED RECEPTOR; HUMAN SERUM-ALBUMIN; CONFORMATIONAL MOBILITY; GLYCOPROTEIN; COLUMN; DRUGS AB A liquid chromatography stationary phase containing immobilized membranes obtained from a cell line that expresses the human organic cation transporter (hOCT1-LAM) has been used to study the binding of the enantiomers of propranolol, atenolol, pseudoephedrine, and alpha-methylbenzylamine to the immobilized hOCT1. Frontal displacement chromatography was used to determine the binding affinities (K-d values), and the data demonstrate that there was an enantioselective difference in the K-d values of the enantiomers of propranolol, atenolol, and pseudoephedrine, while alpha-methylbenzylamine did not significantly bind to the transporter. Competitive inhibition studies with the cell line used to create the chromatographic column demonstrated that, for the enantiomers of propranolol, the ratio of the chromatographically determined K-d values [Kd (+)-(R)-propranolol/Kd (-)-(S)-propranolol = 2.98] reflected an enantioselective difference in the functional activity of the two enantiomers [IC50 (+)-(R)-propranolol/IC50 ((-)-(S)-propranolol) = 2.75]. The chromatographically determined K-d values were used to construct an initial pharmacophore which contains a hydrogen bond donating site that appears to be responsible for the observed enantio selectivity. Published 2005 Wiley-Liss, Inc. C1 NIA, Bioanalyt & Drug Discovery Unit, NIH, Gerontol Res Ctr, Baltimore, MD 21224 USA. Univ Sunderland, Sunderland SR2 7EE, Durham, England. Med Univ Lublin, Lublin, Poland. Shionogi & Co Ltd, Hyogo, Japan. Natl Univ Singapore, Dept Pharm, Singapore 117548, Singapore. RP Wainer, IW (reprint author), NIA, Bioanalyt & Drug Discovery Unit, NIH, Gerontol Res Ctr, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM Wainerir@grc.nia.nih.gov RI Ho, Paul/O-9652-2014 OI Ho, Paul/0000-0001-9213-7116 NR 13 TC 11 Z9 11 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0899-0042 J9 CHIRALITY JI Chirality PD OCT PY 2005 VL 17 IS 8 BP 501 EP 506 DI 10.1002/chir.20195 PG 6 WC Chemistry, Medicinal; Chemistry, Analytical; Chemistry, Organic; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 969PF UT WOS:000232245800012 PM 16113995 ER PT J AU Kump, LI Androudi, SN Foster, CS AF Kump, LI Androudi, SN Foster, CS TI Ocular toxoplasmosis in pregnancy SO CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY LA English DT Article DE ocular inflammation; pregnancy; toxoplasmosis ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; MULTIPLE-SCLEROSIS; CONGENITAL TOXOPLASMOSIS; RHEUMATOID-ARTHRITIS; RETINOCHOROIDITIS; MANAGEMENT; PHARMACOKINETICS; CLINDAMYCIN; DISEASE; WOMEN AB Purpose: To describe the course of ocular toxoplasmosis during pregnancy. Methods: This study was a retrospective, non-comparative case series of four pregnant women who were treated for ocular toxoplasmosis during pregnancy. Results: All of the participants had severe and treatment-resistant toxoplasmic retinochoroiditis during pregnancy, leaving three of them with decreased visual acuity in spite of aggressive therapy. Delivery of the infant appeared to help the recovery in two patients. Conclusions: Pregnant state may provoke the recurrence of ocular toxoplasmosis. C1 Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Ocular Immunol & Uveitis Serv, Boston, MA 02114 USA. RP Kump, LI (reprint author), NEI, NIH, 10 Ctr Dr,Bldg 10,Room 10N112, Bethesda, MD 20892 USA. EM drkump@hotmail.com NR 39 TC 14 Z9 14 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1442-6404 J9 CLIN EXP OPHTHALMOL JI Clin. Exp. Ophthalmol. PD OCT PY 2005 VL 33 IS 5 BP 455 EP 460 DI 10.1111/j.1442-9071.2005.01061.x PG 6 WC Ophthalmology SC Ophthalmology GA 964TC UT WOS:000231902400003 PM 16181268 ER PT J AU Cristini, V Frieboes, HB Gatenby, R Caserta, S Ferrari, M Sinek, J AF Cristini, V Frieboes, HB Gatenby, R Caserta, S Ferrari, M Sinek, J TI Morphologic instability and cancer invasion SO CLINICAL CANCER RESEARCH LA English DT Article ID HUMAN-MELANOMA XENOGRAFTS; HEPATOCYTE GROWTH-FACTOR; ANTIANGIOGENIC THERAPY; TUMOR-GROWTH; SOLID TUMORS; NONLINEAR SIMULATION; IN-VIVO; HYPOXIA; METASTASIS; ANGIOGENESIS AB Purpose: A solid tumor embedded in host tissue is a three-dimensional arrangement of cells and extracellular matrix that acts as a sink of oxygen and cell nutrients, thus establishing diffusional gradients. This and variations in vascular density and blood flow typically produce intratumoral regions of hypoxia and acidosis, and may result in spatially heterogeneous cell proliferation and migration. Here, we formulate the hypothesis that through these mechanisms, microenvironmental substrate gradients may drive morphologic instability with separation of cell clusters from the tumor edge and infiltration into surrounding normal tissue. Experimental Design: We used computer simulations and in vitro experiments. Results: We provide evidence that morphologic instability could be suppressed in vivo by spatially homogeneous oxygen and nutrient supply because normoxic conditions act both by decreasing gradients and increasing cell adhesion and, therefore, the mechanical forces that maintain a well-defined tumor boundary. A properly working tumor microvasculature can help maintain compact noninfiltrating tumor morphologies by minimizing oxygen and nutrient gradients. In contrast, antiarigiogenic therapy, by increasing microenvironmental heterogeneity, may promote morphologic instability, leading to invasive patterns even under conditions in which the overall tumor mass shrinks. Conclusions: We conclude that therapeutic strategies focused solely on reduction of vascular density may paradoxically increase invasive behavior. This theoretical model accounts for the highly variable outcome of antiangiogenic therapy in multiple clinical trials. We propose that antiangiogenic strategies will be more consistently successful when aimed at "normalizing" the vasculature and when combined with therapies that increase cell adhesion so that morphologic instability is suppressed and compact, noninvasive tumor morphologies are enforced. C1 Univ Calif Irvine, Dept Biomed Engn, Irvine, CA 92697 USA. Univ Calif Irvine, Dept Math, Irvine, CA 92697 USA. Univ Arizona, Dept Radiol, Tucson, AZ 85724 USA. Univ Arizona, Dept Appl Math, Tucson, AZ 85724 USA. Univ Naples Federico II, Dept Chem Engn, Naples, Italy. Ohio State Univ, Davis Heart & Lung Res Inst, Columbus, OH 43210 USA. NCI, Bethesda, MD 20892 USA. RP Cristini, V (reprint author), Univ Calif Irvine, Dept Biomed Engn, REC 204, Irvine, CA 92697 USA. EM cristini@math.uci.edu RI Caserta, Sergio/E-4602-2012 OI Caserta, Sergio/0000-0002-4400-0059 NR 58 TC 85 Z9 87 U1 0 U2 8 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT 1 PY 2005 VL 11 IS 19 BP 6772 EP 6779 DI 10.1158/1078-0432.CCR-05-0852 PN 1 PG 8 WC Oncology SC Oncology GA 969MK UT WOS:000232238100006 PM 16203763 ER PT J AU Best, CJM Gillespie, JW Yi, YJ Chandramouli, GVR Perlmutter, MA Gathright, Y Erickson, HS Georgevich, L Tangrea, MA Duray, PH Gonzalez, S Velasco, A Linehan, WM Matusik, RJ Price, DK Figg, WD Emmert-Buck, MR Chuaqui, RF AF Best, CJM Gillespie, JW Yi, YJ Chandramouli, GVR Perlmutter, MA Gathright, Y Erickson, HS Georgevich, L Tangrea, MA Duray, PH Gonzalez, S Velasco, A Linehan, WM Matusik, RJ Price, DK Figg, WD Emmert-Buck, MR Chuaqui, RF TI Molecular alterations in primary prostate cancer after androgen ablation therapy SO CLINICAL CANCER RESEARCH LA English DT Article ID GENE-EXPRESSION ANALYSIS; LASER CAPTURE MICRODISSECTION; CDNA MICROARRAY ANALYSIS; DEPRIVATION THERAPY; NEUROENDOCRINE DIFFERENTIATION; TUMOR ANGIOGENESIS; ALLELIC LOSS; CELL-LINES; BCL-X; GROWTH AB Purpose: After an initial response to androgen ablation, most prostate tumors recur, ultimately progressing to highly aggressive androgen-independent cancer. The molecular mechanisms underlying progression are not well known in part due to the rarity of androgen-independent Samples from primary and-metastatic sites. Experimental Design: We compared the gene expression profiles of 10 androgen-independent primary prostate tumor biopsies with 10 primary, untreated androgen-dependent tumors. Samples were laser capture microdissected, the RNA was amplified, and gene expression was assessed using Affymetrix Human Genome U133A GeneChip. Differential expression was examined with principal component analysis, hierarchical clustering', and Student's t testing. Analysis of gene ontology was done with Expression Analysis Systematic Explorer and gene expression data were integrated with genomic alterations with Differential Gene Locus Mapping. Results: Unsupervised principal component analysis showed that the androgen-dependent and androgen-independent tumors segregated from one another. After filtering the data, 239 differentially expressed genes were identified. Two main gene ontologies were found discordant between androgen-independent and androgen-dependent tumors-macromolecule biosynthesis was clown-regulated and cell adhesion was up-regulated in androgen-independent tumors. Other differentially expressed genes were related to interleukin-6 signaling as well as angiogenesis, cell adhesion, apoptosis, oxidative stress, and hormone response. The Differential Gene Locus Mapping analysis identified nine regions of potential chromosomal deletion in the androgen-independent tumors, including 1p36, 3p2l, 6p2l, 8p2l, 11p15, 11q12,12q23,16q12, and 16q2l. Conclusions: Taken together, these data identify several unique characteristics of androgen-independent prostate cancer that may hold potential for the devellopment,of targeted therapeutic intervention. C1 NCI, Pathogenet Unit, Pathol Lab, NIH, Bethesda, MD 20892 USA. NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. NCI, Mol Pharmacol Sect, Canc Therapeut Branch, NIH, Bethesda, MD 20892 USA. NCI, Sci Applicat Int Corp Frederick Inc, Frederick, MD 21701 USA. Vanderbilt Univ, Vanderbilt Ingram Canc Ctr, Div Med Genet, Dept Med, Nashville, TN USA. Vanderbilt Univ, Vanderbilt Ingram Canc Ctr, Dept Urol Surg, Nashville, TN USA. NCI, Ctr Adv Technol, Gaithersburg, MD USA. Catholic Univ Chile, Dept Pathol, Santiago, Chile. Catholic Univ Chile, Dept Urol, Santiago, Chile. RP Best, CJM (reprint author), NCI, Pathogenet Unit, Pathol Lab, NIH, Bethesda, MD 20892 USA. EM bestcar@mail.nih.gov RI Best, Carolyn/J-4009-2015; Figg Sr, William/M-2411-2016 OI Best, Carolyn/0000-0002-3868-6816; FU Intramural NIH HHS; NCI NIH HHS [R01 CA076142, R01 CA76142-06, Z01 SC010437-05] NR 71 TC 110 Z9 114 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT 1 PY 2005 VL 11 IS 19 BP 6823 EP 6834 DI 10.1158/1078-0432.CCR-05-0585 PN 1 PG 12 WC Oncology SC Oncology GA 969MK UT WOS:000232238100013 PM 16203770 ER PT J AU Tsuda, H Ito, YM Ohashi, Y Wong, KK Hashiguchi, Y Welch, WR Berkowitz, RS Birrer, MJ Mok, SC AF Tsuda, H Ito, YM Ohashi, Y Wong, KK Hashiguchi, Y Welch, WR Berkowitz, RS Birrer, MJ Mok, SC TI Identification of overexpression and amplification of ABCF2 in clear cell ovarian adenocarcinomas by cDNA microarray analyses SO CLINICAL CANCER RESEARCH LA English DT Article ID DISTINCT-HISTOLOGIC-TYPE; COPY-NUMBER CHANGES; DRUG-RESISTANCE; POOR-PROGNOSIS; CLINICAL CHARACTERISTICS; GENE-EXPRESSION; CARCINOMA; CANCER; PROTEIN; CHEMORESISTANCE AB Purpose: Patients with ovarian clear cell adenocarcinoma generally have a poor, response to combination chemotherapy and have overall poorer prognosis than patients with other histologic types of ovarian cancer. Genetic changes in this group of cancer have not been thoroughly explored. Identification of these changes may provide us new therapeutic targets to treat this disease. Experimental Design: Genomic and expression array analyses were applied on 30 clear cell ovarian cancer cases and 19 serous cases using a 10,816-element cDNA microarray platform. Further validation and clinical correlation studies were done on differentially expressed genes that are related to chemo resistance. Results: Based on array analyses, 12 genes showed a significant increase in DNA and mRNA copy number and 5 genes showed a significant decrease in DNA and RNA copy number in clear cell tumors compared with those in the serous type. One of the genes was ABCF2, which belongs to the ATP-binding cassette gene superfamily and has been shown to amplify in other tumor types. Validation studies were done using real-lime quantitative PCR and immunohistochemistry. The results showed significantly higher ABCF2 DNA and mRNA copy number and protein levels in clear cell cases compared with those in serous cases. Furthermore, in 20 clear cell cases with chemoresponse data available, ABCF2 cytoplasmic staining was significantly higher in nonresponders than that in the responders (60.0% versus 28.5%; P = 0.0002). Conclusions: These data suggest that ABCF2 protein may be a prognostic marker for ovarian clear cell ovarian adenocarcinoma. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Lab Gynecol Oncol,Dept Obstet & Gynecol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. Osaka City Gen Hosp, Dept Obstet & Gynecol, Osaka, Japan. NCI, Cell & Canc Biol Branch, Bethesda, MD 20892 USA. Univ Tokyo, Sch Hlth Sci & Nursing, Dept Biostat Epidemiol & Prevent Hlth Sci, Tokyo, Japan. Univ Texas, MD Anderson Canc Ctr, Dept Gynecol Oncol, Lab Mol Cytogenet, Houston, TX 77030 USA. RP Mok, SC (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Lab Gynecol Oncol,Dept Obstet & Gynecol, BLI-447,221 Longwood Ave, Boston, MA 02115 USA. EM scmok@rics.bwh.harvard.edu RI Ito, Yoichi/E-2042-2012; OI Wong, Kwong-Kwok/0000-0002-0375-6669 FU NCI NIH HHS [P50CA165009, R33CA103595] NR 26 TC 51 Z9 53 U1 2 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT 1 PY 2005 VL 11 IS 19 BP 6880 EP 6888 DI 10.1158/1078-0432.CCR-05-0751 PN 1 PG 9 WC Oncology SC Oncology GA 969MK UT WOS:000232238100021 PM 16203778 ER PT J AU Palayoor, ST Arayankalayil, MJ Shoaibi, A Coleman, CN AF Palayoor, ST Arayankalayil, MJ Shoaibi, A Coleman, CN TI Radiation sensitivity of human carcinoma cells transfected with small interfering RNA targeted against cyclooxygenase-2 SO CLINICAL CANCER RESEARCH LA English DT Article ID HYPOXIA-INDUCIBLE FACTORS; PROSTATE-CANCER CELLS; ENZYME-INHIBITORS; IN-VITRO; PROSTAGLANDIN E-2; TUMOR RESPONSE; RADIOTHERAPY; EXPRESSION; GROWTH; COX-2 AB Purpose: Cyclooxygenase-2 (COX-2) is considered a potential target for cancer therapy, because COX-2 levels are elevated in the majority of human tumors compared with the normal tissues. COX-2 inhibitors inhibit tumor growth-and enhance radiation response in vitro as well as in vivo. However, the precise role of COX-2 in radiation response is not clear. The purpose of the present study was to investigate the in vitro radiosensitivity of tumor cells as a function of COX-2 expression. Experimental Design and Results: PC3 and HeLa cells express COX-2 protein constitutively. We silenced the COX-2 gene in these cells using small interfering RNA (si RNA). Transfection of PC3 cells with 100 nmol/L si RNA targeted against COX-2 resulted in reduction of COX-2 protein by 75% and inhibition of arachidonic acid-induced prostaglandin E-2 synthesis by similar to 50% compared with the vehicle control. In HeLa cells, 100 nmol/L COX-2 siRNA inhibited COX-2 protein expression by 80%. Cell cycle analysis showed that transfection with COX-2 si RNA did not alter the cell cycle distribution. Radiosensitivity was determined by clonogenic cell survival assay. There was no significant difference in the radiosensitivity of cells in which COX-2 was silenced compared with the cells transfected vehicle or with negative control siRNAs (enhancement ratio = 1.1). Conclusions: These data indicate that the in Vitro radiosensitivity of tumor cells is minimally dependent on the cellular COX-2 status. Given that a number of potential mechanisms are attributed to COX-2 inhibitors for radiosensitization, specific intervention of COX-2 by RNA interference could help elucidate the precise role of COX-2 in cancer therapy and to optimize strategies for COX-2 inhibition. C1 NCI, NIH, Radiat Oncol Branch, Canc Res Ctr, Bethesda, MD 20892 USA. RP Palayoor, ST (reprint author), NCI, NIH, Radiat Oncol Branch, Canc Res Ctr, Room B3B69,Bldg 10,9000 Rockville Pike, Bethesda, MD 20892 USA. EM Palayoor@mail.nih.gov FU Intramural NIH HHS NR 42 TC 24 Z9 26 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT 1 PY 2005 VL 11 IS 19 BP 6980 EP 6986 DI 10.1158/1078-0432.CCR-05-0326 PN 1 PG 7 WC Oncology SC Oncology GA 969MK UT WOS:000232238100034 PM 16203791 ER PT J AU Lee, FT Mountain, AJ Kelly, MP Hall, C Rigopoulos, A Johns, TG Smyth, FE Brechbiel, MW Nice, EC Burgess, AW Scott, AM AF Lee, FT Mountain, AJ Kelly, MP Hall, C Rigopoulos, A Johns, TG Smyth, FE Brechbiel, MW Nice, EC Burgess, AW Scott, AM TI Enhanced efficacy of radioimmunotherapy with Y-90-CHX-A ''-DTPA-hu3S193 by inhibition of epidermal growth factor receptor (EGFR) signaling with EGFR tyrosine kinase inhibitor AG1478 SO CLINICAL CANCER RESEARCH LA English DT Article; Proceedings Paper CT 10th Conference on Cancer Therapy with Antibodies and Immunoconjugates CY OCT 20-23, 2004 CL Princeton, NJ SP Bristol Myers Squibb, Berlex, biogen idec, Immunomedics Inc, Ctr Mol Med & Immunol, NCI ID MONOCLONAL-ANTIBODIES; RADIATION RESPONSE; ZD1839 IRESSA; PHASE-I; FRACTIONATED RADIOIMMUNOTHERAPY; COLORECTAL-CANCER; TUMOR XENOGRAFTS; BREAST-CANCER; MODULATION; ANTIGENS AB Purpose: Monoclonal antibodies and tyrosine kinase inhibitors specific for the epidermal growth factor receptor (EGFR) have been shown to enhance the effect of external beam radiation on EGFR-positive tumors. The effect of EGFR signaling abrogation by EGFR tyrosine kinase inhibitor on the efficacy of radioimmunotherapy has not been reported previously. This study investigated the effect of EGFR tyrosine kinase inhibition on the efficacy of radioimmunotherapy in a human cancer xenograft model. Experimental Design: The humanized anti - LewisYantibody hu3S193 and the EGFR tyrosine kinase inhibitor AG1478 were studied. BALB/c nude mice were engrafted with A431 squamous carcinoma cells. Initial biodistribution properties of the Y-90-CHX-A"-DTPA-hu3S193 were evaluated in this model. In therapy experiments, cohorts of four to five xenografted mice were treated with saline as placebo, 0.4 mg AG1478 i.p. (six doses over 2 weeks), single i.v.. injections of unlabeled hu3S193, or 90Y-CHX-A"-DTPA-hu3S193 (12.5, 25, 50, or 100 90). The combination of 0.4 mg AG1478 i.p. and 25 mu Ci (Y-CHX)-Y-90-A"-DTPA-hu3S193 i.v. was subsequently evaluated in the A431 model. Results: 90Y-CHX-A"-DTPA-hu3S193 retained excellent immunoreactivity after radiolabeling. The biodistribution study showed excellent uptake in tumor (90.33 +/- 38.84%ID/g) peaking at 24 to 72 hours after injection and with prolonged retention. Y-90-CHX-A"-DTPA-hu3S193 significantly inhibited A431 xenograft growth at 25, 50, and 100 mu Ci doses.The combination of 0.4 mg AG1478 with a single dose of 25 mu Ci 90Y-CHX-A"-DTPA-hu3S193 resulted in a significant enhancement of efficacy compared with either agent alone (P = 0.013). Conclusions: The efficacy of radioimmunotherapy with 90Y-CHX-A"-DTPA-hu3S193 is significantly enhanced by EGFR tyrosine kinase inhibitor AG1478. Further investigations of dosing regimens using EGFR tyrosine kinase inhibitors and radioimmunotherapy in the treatment of EGFR expressing tumors are warranted. C1 Austin Hosp, Tumour Targeting Program, Ludwig Inst Canc Res, Heidelberg, Vic 3084, Australia. Epithelial Biochem Lab, Parkville, Vic, Australia. NCI, Radiat Oncol Branch, Radioimmune & Inorgan Chem Sect, Bethesda, MD 20892 USA. RP Scott, AM (reprint author), Austin Hosp, Tumour Targeting Program, Ludwig Inst Canc Res, Level 1,Harold Stokes Bldg,145-163 Studley Rd, Heidelberg, Vic 3084, Australia. EM andrew.scott@ludwig.edu.au RI Johns, Terrance/C-2441-2008; Nice, Edouard/B-1026-2011 OI Johns, Terrance/0000-0002-8874-4543; FU Intramural NIH HHS NR 48 TC 24 Z9 27 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT 1 PY 2005 VL 11 IS 19 BP 7080S EP 7086S DI 10.1158/1078-0432.CCR-1004-0019 PN 2 PG 7 WC Oncology SC Oncology GA 969MN UT WOS:000232238400007 PM 16203806 ER PT J AU Bowen, RAR Chan, Y Ruddel, ME Hortin, GL Csako, G Demosky, SJ Remaley, AT AF Bowen, RAR Chan, Y Ruddel, ME Hortin, GL Csako, G Demosky, SJ Remaley, AT TI Immunoassay interference by a commonly used blood collection tube additive, the organosilicone surfactant Silwet L-720 SO CLINICAL CHEMISTRY LA English DT Article ID ATOMIC-FORCE MICROSCOPY; IONIZED MAGNESIUM; ANTIBODIES; ANALYZER; IMMOBILIZATION; SEPARATOR AB Background. A small number of immunoassays on several different types of analyzers were recently adversely affected by tube additives in Becton Dickinson TM (BD) Vacutainero SST (TM), SST II, and Microtainer blood collection tubes. We examined the effect of a commonly used tube surfactant, Silwet (TM) L-720, on immunoassays and the mechanism for the interference. Methods: Immunoassays. were performed on serum supplemented with Silwet L-720 on the IMMULITE (TM) 2500 and AxSYM (TM) analyzers. Direct effects of the surfactant on the chemiluminescent detection step of immunoassays and on antibody immobilization on the solid phase were examined. Results: Increasing the final surfactant concentration from 0 to 400 mg/L in serum significantly increased (similar to 51%) the apparent total triiodothyronine (TT,) concentrations measured on the IMMULITE 2500 but not the AxSYM analyzer. Several other competitive, but not noncompetitive, assays were also significantly affected by the surfactant on the IMMULITE 2500 analyzer. The effect was independent of serum components, and the surfactant had no direct effect on chemiluminescence reactions. The capture antibody, however, was displaced from the solid phase by incubation with solutions containing surfactant under conditions similar to the IMMULITE TT, assay. Conclusions: The Silwet L-720 surfactant, which is used to coat the inner surfaces of tubes, appears to account for previously reported immunoassay interference by BD Vacutainer SST blood collection tubes. One of the mechanisms for the interference is the desorption of antibodies from the solid phase by the surfactant. The results identify an important factor in the selection of suitable blood collection tube surfactants and provide an approach for solving similar tube-assay interference problems in the future. (c) 2005 American Association for Clinical Chemistry. C1 Natl Inst Hlth, Dept Lab Med, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. NHLBI, Mol Dis Sect, NIH, Bethesda, MD 20892 USA. RP Remaley, AT (reprint author), Natl Inst Hlth, Dept Lab Med, Warren Grant Magnuson Clin Ctr, Bldg 10,Rm 2C-433,10 Ctr Dr, Bethesda, MD 20892 USA. EM aremaley@nih.gov NR 35 TC 27 Z9 31 U1 1 U2 3 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD OCT PY 2005 VL 51 IS 10 BP 1874 EP 1882 DI 10.1373/clinchem.2005.055400 PG 9 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 968YE UT WOS:000232198600018 PM 16099932 ER PT J AU Lowenthal, MS Mehta, AI Frogale, K Bandle, RW Araujo, RP Hood, BL Veenstra, TD Conrads, TP Goldsmith, P Fishman, D Petricoin, EF Liotta, LA AF Lowenthal, MS Mehta, AI Frogale, K Bandle, RW Araujo, RP Hood, BL Veenstra, TD Conrads, TP Goldsmith, P Fishman, D Petricoin, EF Liotta, LA TI Analysis of albumin-associated peptides and proteins from ovarian cancer patients SO CLINICAL CHEMISTRY LA English DT Article; Proceedings Paper CT 37th Annual Oak Ridge Conference CY APR 14-15, 2005 CL Baltimore, MD SP Amer Assoc Clin Chem ID TANDEM MASS-SPECTROMETRY; HUMAN PLASMA PROTEOME; HUMAN SERUM PROTEOME; BREAST-CANCER; YEAST PROTEOME; IN-VIVO; BINDING; IDENTIFICATION; CHROMATOGRAPHY; AFFINITY AB Background: Albumin binds low-molecular-weight molecules, including proteins and peptides, which then acquire its longer half-life, thereby protecting the bound species from kidney clearance. We developed an experimental method to isolate albumin in its native state and to then identify [mass spectrometry (MS) sequencing] the corresponding bound low-molecular-weight molecules. We used this method to analyze pooled sera from a human disease study set (high-risk persons without cancer, n = 40; stage I ovarian cancer, n = 30; stage III ovarian cancer, n = 40) to demonstrate the feasibility of this approach as a discovery method. Methods: Albumin was isolated by solid-phase affinity capture under native binding and washing conditions. Captured albumin-associated proteins and peptides were separated by gel electrophoresis and subjected to iterative MS sequencing by microcapillary reversed-phase tandem MS. Selected albumin-bound protein fragments were confirmed in human sera by Western blotting and immunocompetition. Results: In total, 1208 individual protein sequences were predicted from all 3 pools. The predicted sequences were largely fragments derived from proteins with diverse biological functions. More than one third of these fragments were identified by multiple peptide sequences, and more than one half of the identified species were in vivo cleavage products of parent proteins. An estimated 700 serum peptides or proteins were predicted that had not been reported in previous serum databases. Several proteolytic fragments of larger molecules that may be cancer-related were confirmed immunologically in blood by Western blotting and peptide immunocompetition. BRCA2, a 390-kDa low-abundance nuclear protein linked to cancer susceptibility, was represented in sera as a series of specific fragments bound to albumin. Conclusion: Carrier-protein harvesting provides a rich source of candidate peptides and proteins with potential diverse tissue and cellular origins that may reflect important disease-related information. (c) 2005 American Association for Clinical Chemistry. C1 George Mason Univ, Ctr Appl Prote & Mol Med, Manassas, VA 20110 USA. NCI, Pathol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. Tufts Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02111 USA. NYU, Natl Ovarian Canc Early Detect Program, New York, NY USA. NCI, SAIC, Biomed Prote Program, Frederick, MD 21701 USA. RP Petricoin, EF (reprint author), George Mason Univ, Ctr Appl Prote & Mol Med, Manassas, VA 20110 USA. EM epetrico@gmu.edu; lliotta@gmu.edu NR 46 TC 134 Z9 144 U1 2 U2 10 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 2005 VL 51 IS 10 BP 1933 EP 1945 DI 10.1373/clinchem.2005.052944 PG 13 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 968YE UT WOS:000232198600035 PM 16099937 ER PT J AU Lopez, MF Mikulskis, A Kuzdzal, S Bennett, DA Kelly, J Golenko, E DiCesare, J Denoyer, E Patton, WF Ediger, R Sapp, L Ziegert, T Lynch, C Kramer, S Whiteley, GR Wall, MR Mannion, DP Della Cioppa, G Rakitan, JS Wolfe, GM AF Lopez, MF Mikulskis, A Kuzdzal, S Bennett, DA Kelly, J Golenko, E DiCesare, J Denoyer, E Patton, WF Ediger, R Sapp, L Ziegert, T Lynch, C Kramer, S Whiteley, GR Wall, MR Mannion, DP Della Cioppa, G Rakitan, JS Wolfe, GM TI High-resolution serum proteomic profiling of Alzheimer disease samples reveals disease-specific, carrier-protein-bound mass signatures SO CLINICAL CHEMISTRY LA English DT Article; Proceedings Paper CT 37th Annual Oak Ridge Conference CY APR 14-15, 2005 CL Baltimore, MD SP Amer Assoc Clin Chem ID OVARIAN-CANCER; CLINICAL PROTEOMICS; PATTERNS; DIAGNOSIS; MARKERS; ONSET AB Background. Researchers typically search for disease markers using a "targeted" approach in which a hypothesis about the disease mechanism is tested and experimental results either confirm or disprove the involvement of a particular gene or protein in the disease. Recently, there has been interest in developing disease diagnostics based on unbiased quantification of differences in global patterns of protein and peptide masses, typically in blood from individuals with and without disease. We combined a suite of methods and technologies, including novel sample preparation based on carrier-protein capture and biomarker enrichment, high-resolution mass spectrometry, a unique cohort of well-characterized persons with and without Alzheimer disease (AD), and powerful bioinformatic analysis, that add statistical and procedural robustness to biomarker discovery from blood. Methods: Carrier-protein-bound peptides were isolated from serum samples by affinity chromatography, and peptide mass spectra were acquired by a matrixassisted laser desorptionlionization (MALDI) orthogo-nal time-of-flight (O-TOF) mass spectrometer capable of collecting data over a broad mass range (100 to > 300 000 Da) in a single acquisition. Discriminatory analysis of mass spectra was used to process and analyze the raw mass spectral data. Results: Coupled with the biomarker enrichment protocol, the high-resolution MALDI O-TOF mass spectra provided informative, reproducible peptide signatures. The raw mass spectra were analyzed and used to build discriminant disease models that were challenged with blinded samples for classification. Conclusions: Carrier-protein enrichment of disease biomarkers coupled with high-resolution mass spectrometry and discriminant pattern analysis is a powerful technology for diagnostics and population screening. The mass fingerprint model successfully classified blinded AD patient and control samples with high sensitivity and specificity. (c) 2005 American Association for Clinical Chemistry. C1 PerkinElmer Life & Analyt Sci, Boston, MA 02118 USA. PerkinElmer Life & Analyt Sci, Shelton, CT USA. Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA. PerkinElmer Life & Analyt Sci, Beaconsfield, Bucks, England. SAIC Frederick Inc, NCI, Clin Prote Reference Lab, Gaithersburg, MD USA. Predict Diagnost Inc, Vacaville, CA USA. RP Lopez, MF (reprint author), PerkinElmer Life & Analyt Sci, 249 Albany St, Boston, MA 02118 USA. EM mary.lopez@perkinelmer.com FU NIA NIH HHS [P30 AG10161, R01 AG15819] NR 27 TC 104 Z9 110 U1 1 U2 7 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 2005 VL 51 IS 10 BP 1946 EP 1954 DI 10.1373/clinchem.2005.053090 PG 9 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 968YE UT WOS:000232198600036 PM 16081505 ER PT J AU Chrousos, GP Kaltsas, G AF Chrousos, GP Kaltsas, G TI Post-SARS sickness syndrome manifestations and endocrinopathy: how, why, and so what? SO CLINICAL ENDOCRINOLOGY LA English DT Editorial Material ID PITUITARY-ADRENAL AXIS; SECRETION; FATIGUE; GLUCOCORTICOIDS; INTERLEUKIN-6; STRESS; PAIN C1 Univ Athens, Sch Med, Dept Paediat 1, Aghia Sophia Childrens Hosp, GR-11527 Athens, Greece. NIH, Bethesda, MD 20892 USA. RP Chrousos, GP (reprint author), Univ Athens, Sch Med, Dept Paediat 1, Aghia Sophia Childrens Hosp, GR-11527 Athens, Greece. EM chrousge@med.uoa.gr NR 12 TC 1 Z9 1 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0300-0664 J9 CLIN ENDOCRINOL JI Clin. Endocrinol. PD OCT PY 2005 VL 63 IS 4 BP 363 EP 365 DI 10.1111/j.1365-2265.2005.02361.x PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 967OX UT WOS:000232102200001 PM 16181227 ER PT J AU Biesecker, LG AF Biesecker, LG TI Mapping phenotypes to language: a proposal to organize and standardize the clinical descriptions of malformations SO CLINICAL GENETICS LA English DT Article DE malformations; terminology; nomenclature ID FUNCTIONAL GENOMICS; MUTATIONS AB Recent developments in molecular biology have markedly speeded the processes involved in determining the molecular etiology of human Mendelian disorders. Nowhere are these changes more evident than in the field that is variously termed molecular dysmorphology, human morphogenesis, or human developmental biology. In contrast to the rapid changes in molecular genetics analysis, the processes and approaches of the clinical component of molecular dysmorphology have not changed substantially, and clinical analysis is therefore becoming relatively slower than molecular discovery. If clinical discovery is to maintain its deserved position at the forefront of human genetics research, new methods must be developed to acquire, archive, and analyze these data. The limitations of current phenotyping, specifically, the limitations of the collection and archiving of clinical data in medical journal case reports and case series manuscripts are demonstrated. Several provocative approaches that have been proposed to advance the field of clinical analysis are reviewed. Lastly, a specific proposal for a system of clinical analysis and archiving of data on human pleiotropic developmental anomaly syndromes is proposed to address these limitations. C1 NHGRI, NIH, Bethesda, MD 20892 USA. RP Biesecker, LG (reprint author), NHGRI, NIH, 49 Convent Dr, Bethesda, MD 20892 USA. EM leslieb@helix.nih.gov NR 21 TC 21 Z9 22 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0009-9163 J9 CLIN GENET JI Clin. Genet. PD OCT PY 2005 VL 68 IS 4 BP 320 EP 326 DI 10.1111/j.1399-0004.2005.00509.x PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 960VS UT WOS:000231621900003 PM 16143016 ER PT J AU Jain, S Wood, NW Healy, DG AF Jain, S Wood, NW Healy, DG TI Molecular genetic pathways in Parkinson's disease: a review SO CLINICAL SCIENCE LA English DT Review DE alpha-synuclein; dardarin; genetic basis; Lewy body; Mendelian genetics; parkin; Parkinson's disease ID EARLY-ONSET PARKINSONISM; AUTOSOMAL-DOMINANT PARKINSONISM; PROGRESSIVE SUPRANUCLEAR PALSY; TERMINAL HYDROLASE-L1 GENE; PATHOGENIC DJ-1 MUTATIONS; ALPHA-SYNUCLEIN PROMOTER; COMMON LRRK2 MUTATION; FAMILIAL AGGREGATION; UCH-L1 GENE; S18Y POLYMORPHISM AB Major progress has been made in the last decade in understanding the genetic basis of PD (Parkinson's disease) with five genes unequivocally associated with disease. As a result, multiple pathways have been implicated in the pathogenesis of PD, including proteasome impairment and mitochondrial dysfunction. Although Mendelian genetics has been successful in establishing a genetic predisposition for familial PD, this has not been reiterated in the sporadic form. In fact no genetic factors have been unequivocally associated with increased risk for sporadic PD. The difficulty in identifying susceptibility factors in PD has not only been because of numerous underpowered studies, but we have been unable to dissect out the genetic component in a multifactorial disease. This review aims to summarize the genetic findings within PD. C1 Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England. NIA, NIH, Bethesda, MD 20892 USA. UCL, Reta Lila Weston Inst Neurol Sci, London W1T 4JF, England. RP Wood, NW (reprint author), Inst Neurol, Dept Mol Neurosci, Queen Sq, London WC1N 3BG, England. EM n.wood@ion.ucl.ac.uk RI Wood, Nicholas/C-2505-2009 OI Wood, Nicholas/0000-0002-9500-3348 NR 122 TC 23 Z9 25 U1 1 U2 3 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0143-5221 J9 CLIN SCI JI Clin. Sci. PD OCT PY 2005 VL 109 IS 4 BP 355 EP 364 DI 10.1042/CS0050106 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 974BX UT WOS:000232567400002 PM 16171459 ER PT J AU Field, D Garrity, G Morrison, N Selengut, J Sterk, P Tatusova, T Thomson, N AF Field, D Garrity, G Morrison, N Selengut, J Sterk, P Tatusova, T Thomson, N TI eGenomics: Cataloguing our complete genome collection SO COMPARATIVE AND FUNCTIONAL GENOMICS LA English DT Editorial Material DE genomes; bioinformatics; metadata; data standards; genomic databases; computational biology; ecology; environment C1 Oxford Ctr Ecol & Hydrol, Mol Evolut & Bioinformat Sect, Oxford OX1 3SR, England. Michigan State Univ, Dept Microbiol & Mol Genet, E Lansing, MI 48824 USA. Univ Manchester, Sch Comp Sci, Manchester M13 9PL, Lancs, England. Oxford Ctr Ecol & Hydrol, NERC, Environm Bioinformat Ctr, Oxford OX1 3SR, England. Inst Genom Res, Rockville, MD 20850 USA. EMBL Outstn, EBI, Cambridge CB10 1SD, England. Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. Wellcome Trust Sanger Inst, Pathogen Sequencing Unit, Cambridge CB10 1SA, England. RP Field, D (reprint author), Oxford Ctr Ecol & Hydrol, Mol Evolut & Bioinformat Sect, Mansfield Rd, Oxford OX1 3SR, England. EM dfield@ceh.ac.uk RI Field, Dawn/C-1653-2010; Garrity, George/F-7551-2013; OI Garrity, George/0000-0002-4465-7034; Sterk, Peter/0000-0003-1668-7778 NR 2 TC 4 Z9 4 U1 0 U2 0 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1531-6912 J9 COMP FUNCT GENOM JI Compar. Funct. Genom. PD OCT-DEC PY 2005 VL 6 IS 7-8 BP 363 EP 368 DI 10.1002/cfg.494 PG 6 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 019BW UT WOS:000235811600003 PM 18629208 ER PT J AU Driesel, W Merkle, H Hetzer, S Riemer, T Zysset, S Moller, HE AF Driesel, W Merkle, H Hetzer, S Riemer, T Zysset, S Moller, HE TI Reengineered helmet coil for human brain studies at 3 tesla SO CONCEPTS IN MAGNETIC RESONANCE PART B-MAGNETIC RESONANCE ENGINEERING LA English DT Article DE helmet coil; high-field imaging; human brain; radiofrequency field homogeneity; specific absorption rate ID VECTOR FINITE-ELEMENTS; TO-NOISE RATIO; MAGNETIC-FIELD; MOTOR CORTEX; INTERFERENCE; CONTRAST; SAMPLES; TASK; FMRI AB We describe the further development of a circularly polarized helmet coil for magnetic resonance imaging (MRI) of the human brain at 3 T. The coil is used in transmit and receive (transceive) mode, a useful alternative over commercially available quadrature headcoils with scanners where phased arrays are unavailable. The coil is simple to build. its structure is based on an assembly of two coplanar dual-loop coils of the split-circle design, which are arranged in crossed fashion. Both coils circumscribe dome-like the human head. Because of the symmetry of the assembly, a high degree of circularly polarized radiofrequency (RF) is obtained within the brain. Bench and in situ measurements of the RF magnetic field, B, indicated good axial homogeneity and a moderate gradient along the symmetry axis. Compared to a commercial birdcage coil, the signal-to-noise ratio was increased up to a factor of 1.7 as a result of its superior filling factor. Initial applications in healthy volunteers included anatomical MRI and functional imaging with a cognitive paradigm. (c) 2005 Wiley Periodicals, Inc. C1 Max Planck Inst Human Cognit & Brain Sci, D-04103 Leipzig, Germany. NINDS, NIH, Bethesda, MD 20892 USA. Univ Leipzig, Grp Clin NMR Spect, Interdisciplinary Ctr Clin Res, D-7010 Leipzig, Germany. Univ Hosp Munster, Dept Radiol, Munster, Germany. RP Driesel, W (reprint author), Max Planck Inst Human Cognit & Brain Sci, D-04103 Leipzig, Germany. EM driesel@cbs.mpg.de; merkleh@mail.nih.gov RI Moller, Harald/A-1565-2008 OI Moller, Harald/0000-0002-5659-1925 NR 38 TC 6 Z9 6 U1 1 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-5031 J9 CONCEPT MAGN RESON B JI Concepts Magn. Reson. Part B PD OCT PY 2005 VL 27B IS 1 BP 64 EP 74 DI 10.1002/cmr.b.20052 PG 11 WC Chemistry, Physical; Instruments & Instrumentation; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Chemistry; Instruments & Instrumentation; Physics; Spectroscopy GA 981RB UT WOS:000233104600007 ER PT J AU Orwoll, E Blank, JB Barrett-Connor, E Cauley, J Cummings, S Ensrud, K Lewis, C Cawthon, PM Marcus, R Marshall, LM McGowan, J Phipps, K Sherman, S Stefanick, ML Stone, K AF Orwoll, E Blank, JB Barrett-Connor, E Cauley, J Cummings, S Ensrud, K Lewis, C Cawthon, PM Marcus, R Marshall, LM McGowan, J Phipps, K Sherman, S Stefanick, ML Stone, K TI Design and baseline characteristics of the osteoporotic fractures in men (MrOS) study - A large observational study of the determinants of fracture in older men SO CONTEMPORARY CLINICAL TRIALS LA English DT Article DE osteoporosis; fractures; men; epidemiology ID HIP FRACTURE; WHITE WOMEN; US ADULTS; RELIABILITY; VALIDITY; STATES AB Very little information is available to direct the prevention or management of osteoporosis in men. The Osteoporotic Fractures in Men (MrOS) Study is a prospective cohort study designed to examine the extent to which fracture risk is related to bone mass, bone geometry, lifestyle, anthropometric and neuromuscular measures, and fall propensity, as well as to determine how fractures affect quality of life in men. The study is also designed to understand how osteoporosis is related to prostate disease. At baseline, participants completed questionnaires regarding medical history, medications, physical activity, diet, alcohol intake, and cigarette smoking. Objective measures of anthropometric, neuromuscular, vision, strength, and cognitive variables were obtained. Skeletal assessments included DEXA, calcaneal ultrasound, and vertebral radiographs. Vertebral and proximal femoral QCT was performed on a subset (65%). Serum, urine, and DNA specimens were collected. After the baseline assessments, a questionnaire is mailed to participants every 4 months to ascertain incident falls, fractures, prostate cancer, and deaths. After an average of 4.5 years, participants are scheduled to return for a second comprehensive visit. Men were eligible if >= 65 years. 5995 men enrolled with a mean (+/- SD) age of 73.7 (+/- 5.9) years, 11% of which were minorities. Most rated their health as good/excellent. Few were current smokers, although 59% had smoked previously, and 35% reported no alcohol intake, while 47% consumed at least 2 drinks per week. The mean (range) body mass index was 26.9 kg/m(2) (17-56). A non-traumatic fracture after age 50 was reported by 17% of the cohort. The MrOS cohort should provide valuable information concerning the determinants of fracture in men and should help set the stage for the development of effective methods to identify those at risk. (c) 2005 Elsevier Inc. All rights reserved. C1 Oregon Hlth Sci Univ, Portland, OR 97239 USA. Univ Calif San Diego, San Diego, CA 92103 USA. Univ Pittsburgh, Pittsburgh, PA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. VA Med Ctr, Minneapolis, MN USA. Univ Minnesota, Minneapolis, MN USA. Univ Alabama, Birmingham, AL USA. Stanford Univ, Palo Alto, CA 94304 USA. NIAMSD, NIH, Bethesda, MD 20892 USA. RP Orwoll, E (reprint author), Oregon Hlth Sci Univ, CR 113,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM orwoll@ohsu.edu RI Cauley, Jane/N-4836-2015; OI Cauley, Jane/0000-0003-0752-4408; Orwoll, Eric/0000-0002-8520-7355 FU NCRR NIH HHS [M01 RR000334]; NIA NIH HHS [AG18197]; NIAMS NIH HHS [AR45583, AR45580, AR45614, AR45632, AR45654, U01-AR45647] NR 25 TC 349 Z9 350 U1 0 U2 17 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7144 J9 CONTEMP CLIN TRIALS JI Contemp. Clin. Trials PD OCT PY 2005 VL 26 IS 5 BP 569 EP 585 DI 10.1016/j.cct.2005.05.006 PG 17 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 966MF UT WOS:000232023400007 PM 16084776 ER PT J AU Grafman, J AF Grafman, J TI Where does consciousness come from? SO CORTEX LA English DT Editorial Material C1 NINDS, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA. RP Grafman, J (reprint author), NINDS, Cognit Neurosci Sect, NIH, Bldg 10,Room 5C205,MSC 1440, Bethesda, MD 20892 USA. EM grafmanj@ninds.nih.gov OI Grafman, Jordan H./0000-0001-8645-4457 NR 0 TC 0 Z9 0 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 2005 VL 41 IS 5 BP 617 EP 618 DI 10.1016/S0010-9452(08)70278-8 PG 2 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 971DL UT WOS:000232361400001 PM 16209325 ER PT J AU Grounds, RM Bolan, C AF Grounds, RM Bolan, C TI Clinical experiences and current evidence for therapeutic recombinant factor VIIa treatment in nontrauma settings SO CRITICAL CARE LA English DT Review ID ACTIVATED FACTOR-VII; THREATENING POSTPARTUM HEMORRHAGE; ORTHOTOPIC LIVER-TRANSPLANTATION; ACUTE INTRACEREBRAL HEMORRHAGE; DOUBLE-BLIND; BLEEDING DISORDERS; PROTHROMBIN TIME; TRANSFUSION MEDICINE; RAPID CORRECTION; COAGULATION AB The hemostatic properties of recombinant activated factor VII ( rFVIIa) are established in patients with inherited or acquired hemophilia with inhibitors and in patients with congenital factor VII deficiencies. Emerging clinical evidence suggests that there may be a wider role for rFVIIa in the management of hemorrhage associated with traumatic injury/accident and severe bleeding associated with critical surgery. This article considers recent data from studies in which rFVIIa was used in an attempt to control bleeding in clinical situations as diverse as coagulopathy associated with chronic liver disease, massive perioperative bleeding and bleeding during prostatectomy, organ transplantation and orthopedic surgery, uncontrollable obstetric hemorrhage, and intracerebral hemorrhage. In nontrauma settings involving acute and potentially life threatening bleeding, there may be a place for rFVIIa as adjunctive therapy in the control of hemostasis. C1 Univ London St Georges Hosp, Adult Intens Care Unit, London, England. USA, Med Corps, Bethesda, MD USA. NIH, Blood Serv Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. RP Grounds, RM (reprint author), Univ London St Georges Hosp, Adult Intens Care Unit, London, England. EM m.grounds@blueyonder.co.uk NR 52 TC 9 Z9 9 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1466-609X J9 CRIT CARE JI Crit. Care PD OCT PY 2005 VL 9 SU 5 BP S29 EP S36 DI 10.1186/cc3783 PG 8 WC Critical Care Medicine SC General & Internal Medicine GA 024SF UT WOS:000236215700005 PM 16221317 ER PT J AU Safdar, N Dezfulian, C Collard, HR Saint, S AF Safdar, N Dezfulian, C Collard, HR Saint, S TI Clinical and economic consequences of ventilator-associated pneumonia: A systematic review SO CRITICAL CARE MEDICINE LA English DT Review DE ventilator-associated pneumonia; prevention; prospective cohort; nosocomial pneumonia; outcomes; mortality; cost ID INTENSIVE-CARE-UNIT; HOSPITAL-ACQUIRED PNEUMONIA; STRESS-ULCER PROPHYLAXIS; CRITICALLY-ILL PATIENTS; SELECTIVE DIGESTIVE DECONTAMINATION; CONTINUOUS MECHANICAL VENTILATION; RANDOMIZED CONTROLLED TRIAL; PROTECTED SPECIMEN BRUSH; MULTIPLE TRAUMA PATIENTS; EVERY 48 HOURS AB Background: Ventilator-associated pneumonia (VAP) is the most common nosocomial infection in critically ill patients. The clinical and economic consequences of VAP are unclear, with a broad range of values reported in the literature. Objective: To perform a systematic review to determine the incidence of VAP and its attributable mortality rate, length of stay, and costs. Data Source: Computerized PUBMED and MEDLINE search supplemented by manual searches for relevant articles, limited to articles published after 1990. Study Selection: English-language observational studies and randomized trials that provided data on the incidence of VAP were included. Matched cohort studies were included for calculation of attributable mortality rate and length of stay. Data Extraction: Data were extracted on patient population, diagnostic criteria for VAP, incidence, outcome, type of intensive care unit, and study design. Data Synthesis: The cumulative incidence of VAP was calculated by combining the results of several studies using standard formulas for combining proportions, in which the weighted average and variance are calculated. Results from studies comparing intensive care unit and hospital mortality due to YAP, additional length of stay, and additional days of mechanical ventilation were pooled using a random effects model, with assessment of heterogeneity. Results: Our findings indicate a) between 10% and 20% of patients receiving > 48 hrs of mechanical ventilation will develop VAP; b) critically ill patients who develop YAP appear to be twice as likely to die compared with similar patients without VAP (pooled odds ratio, 2.03; 95% confidence interval, 1.16-3.56); c) patients with VAP have significantly longer intensive care unit lengths of stay (mean = 6.10 days; 95% confidence interval, 5.32-6.87 days); and d) patients who develop VAP incur >=$10,019 in additional hospital costs. Conclusions: Ventilator-associated pneumonia occurs in a considerable proportion of patients undergoing mechanical ventilation and is associated with substantial morbidity, a two-fold mortality rate, and excess cost. Given these findings, strategies that effectively prevent VAP are urgently needed. C1 Univ Wisconsin, Infect Dis Sect, Dept Med, Sch Med, Madison, WI 53792 USA. Natl Inst Hlth, Dept Crit Care Med, Bethesda, MD USA. Johns Hopkins Univ Hosp, Div Pediat Anesthesia & Crit Care, Baltimore, MD 21287 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Michigan, Ann Arbor VA Med Ctr, Sch Med, Ann Arbor, MI 48109 USA. Univ Michigan, Sch Med, Patient Safety Enhancement Program, Ann Arbor, MI 48109 USA. Univ Michigan, Div Gen Med, Ann Arbor, MI 48109 USA. RP Univ Wisconsin, Infect Dis Sect, Dept Med, Sch Med, 600 Highland Ave,H4-572, Madison, WI 53792 USA. EM ns2@medicine.wisc.edu OI Dezfulian, Cameron/0000-0002-4486-0446 FU AHRQ HHS [P20 HS 11540] NR 124 TC 492 Z9 533 U1 3 U2 19 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0090-3493 EI 1530-0293 J9 CRIT CARE MED JI Crit. Care Med. PD OCT PY 2005 VL 33 IS 10 BP 2184 EP 2193 DI 10.1097/01.CCM.0000181731.53912.D9 PG 10 WC Critical Care Medicine SC General & Internal Medicine GA 019YV UT WOS:000235875600005 PM 16215368 ER PT J AU Salgado, CD O'Grady, N Farr, BM AF Salgado, CD O'Grady, N Farr, BM TI Prevention and control of antimicrobial-resistant infections in intensive care patients SO CRITICAL CARE MEDICINE LA English DT Review DE antimicrobial resistance; intensive care; infection ID VENTILATOR-ASSOCIATED PNEUMONIA; STAPHYLOCOCCUS-AUREUS BACTEREMIA; BLOOD-STREAM INFECTIONS; ENTEROCOCCUS-FAECIUM BACTEREMIA; CENTRAL VENOUS CATHETERS; CRITICALLY-ILL PATIENTS; AFFAIRS MEDICAL-CENTER; METHICILLIN-RESISTANT; VANCOMYCIN-RESISTANT; RISK-FACTORS AB Objective: To review the literature summarizing important aspects of infection control in the critical care setting and to provide recommendations to reduce infections with resistant bacteria in the intensive care unit. Data Source: Computer searches of MEDLINE, EMBASE, and the Cochrane Library. Data: The frequency of antibiotic-resistant, health care-associated infections has increased every year for the past 2 decades. Infections with antibiotic-resistant organisms have been linked to increases in morbidity, length of hospitalization, increased healthcare costs, and increased mortality. A comprehensive approach is necessary to prevent antimicrobial resistance in ICUs. This includes (1) preventing infections; (2) diagnosing and treating infections appropriately; (3) using antimicrobials wisely; and (4) preventing transmission. Conclusions: The reservoirs for antibiotic-resistant organisms are colonized patients, and the vectors are often healthcare workers. This places an enormous responsibility on healthcare providers to protect their patients. Clinicians must recognize the importance of adhering to the recommendations in the Centers for Disease Control's Campaign to Prevent Antimicrobial Resistance in the healthcare setting. C1 Med Univ S Carolina, Charleston, SC 29425 USA. NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. Univ Virginia Hlth Syst, Charlottesville, VA USA. RP Salgado, CD (reprint author), Med Univ S Carolina, Charleston, SC 29425 USA. NR 147 TC 23 Z9 29 U1 1 U2 2 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 2005 VL 33 IS 10 BP 2373 EP 2382 DI 10.1097/01.CCM.0000181727.04501.F3 PG 10 WC Critical Care Medicine SC General & Internal Medicine GA 019YV UT WOS:000235875600031 PM 16215395 ER PT J AU Eichacker, PQ Danner, RL Suffredini, AF Cui, XZ Natanson, C AF Eichacker, PQ Danner, RL Suffredini, AF Cui, XZ Natanson, C TI Reassessing recombinant human activated protein C for sepsis: Time for a new randomized controlled trial SO CRITICAL CARE MEDICINE LA English DT Editorial Material DE recombinant human activated protein C; ENHANCE; PROWESS ID SAFETY C1 NIH, Crit Care Med Dept, Warren C Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Eichacker, PQ (reprint author), NIH, Crit Care Med Dept, Warren C Magnuson Clin Ctr, Bldg 10, Bethesda, MD 20892 USA. NR 11 TC 35 Z9 36 U1 1 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 2005 VL 33 IS 10 BP 2426 EP 2428 DI 10.1097/01.CCM.0000183002.26587.FF PG 3 WC Critical Care Medicine SC General & Internal Medicine GA 019YV UT WOS:000235875600046 PM 16215410 ER PT J AU Seed, J Carney, EW Corley, RA Crofton, KM DeSesso, JM Foster, PMD Kavlock, R Kimmel, G Klaunig, J Meek, ME Preston, RJ Slikker, W Tabacova, S Williams, GM Wiltse, J Zoeller, RT Fenner-Crisp, P Patton, DE AF Seed, J Carney, EW Corley, RA Crofton, KM DeSesso, JM Foster, PMD Kavlock, R Kimmel, G Klaunig, J Meek, ME Preston, RJ Slikker, W Tabacova, S Williams, GM Wiltse, J Zoeller, RT Fenner-Crisp, P Patton, DE TI Overview: Using mode of action and life stage information to evaluate the human relevance of animal toxicity data SO CRITICAL REVIEWS IN TOXICOLOGY LA English DT Review DE developmental window; human relevance framework; noncancer modes of action; risk assessment ID FRAMEWORK AB A complete mode of action human relevance analysis-as distinct from mode of action (MOA) analysis alone-depends on robust information on the animal MOA, as well as systematic comparison of the animal data with corresponding information from humans. In November 2003, the International Life Sciences Institute's Risk Science Institute (ILSI RSI) published a 2-year study using animal and human MOA information to generate a four-part Human Relevance Framework (HRF) for systematic and transparent analysis of MOA data and information. Based mainly on non-DNA-reactive carcinogens, the HRF features a "concordance" analysis of MOA information from both animal and human sources, with a focus on determining the appropriate role for each MOA data set in human risk assessment. With MOA information increasingly available for risk assessment purposes, this article illustrates the further applicability of the HRF for reproductive, developmental, neurologic, and renal endpoints, as well as cancer. Based on qualitative and quantitative MOA considerations, the MOA/human relevance analysis also contributes to identifying data needs and issues essential for the dose-response and exposure assessment steps in the overall risk assessment. C1 US EPA, Washington, DC 20460 USA. Dow Chem Co USA, Midland, MI 48674 USA. Pacific NW Natl Lab, Richland, WA 99352 USA. US EPA, Res Triangle Pk, NC 27711 USA. Mitretek Syst, Falls Church, VA USA. NIEHS, Res Triangle Pk, NC 27709 USA. Indiana Univ, Sch Med, Indianapolis, IN USA. Hlth Canada, Ottawa, ON K1A 0L2, Canada. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. US FDA, Rockville, MD 20857 USA. New York Med Coll, Valhalla, NY 10595 USA. RP Patton, DE (reprint author), ILSI Risk Sci Inst, 1 Thomas Circle NW, Washington, DC 20005 USA. EM dpatton@ilsi.org RI Crofton, Kevin/J-4798-2015 OI Crofton, Kevin/0000-0003-1749-9971 NR 7 TC 48 Z9 50 U1 0 U2 4 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1040-8444 J9 CRIT REV TOXICOL JI Crit. Rev. Toxicol. PD OCT-NOV PY 2005 VL 35 IS 8-9 BP 663 EP 672 DI 10.1080/10408440591007133 PG 10 WC Toxicology SC Toxicology GA 993UH UT WOS:000233980100001 ER PT J AU Foster, PMD AF Foster, PMD TI Mode of action: Impaired fetal Leydig cell function - Effects on male reproductive development produced by certain phthalate esters SO CRITICAL REVIEWS IN TOXICOLOGY LA English DT Review DE di-n-butyl phthalate; endocrine disruptors; human relevance; mechanisms ID N-BUTYL PHTHALATE; IN-UTERO EXPOSURE; TESTICULAR DYSGENESIS SYNDROME; ACTIVATED RECEPTOR-ALPHA; EXPERT PANEL REPORT; DI(N-BUTYL) PHTHALATE; DI(2-ETHYLHEXYL) PHTHALATE; DIBUTYL PHTHALATE; GENE-EXPRESSION; MOLECULAR-BASIS AB Certain phthalate esters (di-2-ethylhexyl; di-n-butyl and butyl benzyl) have profound effects on the developing male reproductive system when administered orally to pregnant experimental animals during a critical window of development. These esters produce a syndrome of adverse effects that are characteristic of a disturbance in androgen-mediated development and include a variety of reproductive tract malformations and effects on developmental phenotypic markers. A testicular dysgenesis syndrome has been proposed to explain the secular increases in a number of human male reproductive deficits, including decreased semen parameters, increased incidence of cryptorchidism and hypospadias (two of the most common human birth defects), and increased incidence of testicular (germ cell derived) cancer. The rodent phthalate data lend support to the hypothesis. This example illustrates a number of points in the use of the Human Relevance Framework. First, chemical agents may have more than one mode of action (MOA): for example, phthalate-induced peroxisome proliferation leading to hepatocarcinogensis, compared with the induction of developmental effects via effects on androgen signaling. Second, the case demonstrates the life-stage sensitivity of the response to these compounds. Third, because humans may be exposed to multiple phthalate esters producing adverse effects on reproductive development, these compounds may be useful in testing the utility of the Human Relevance Framework (HRF) approach for evaluating cumulative and aggregate risk. C1 NIEHS, Res Triangle Pk, NC 27709 USA. RP Foster, PMD (reprint author), NIEHS, POB 12233,Mail Code E-106, Res Triangle Pk, NC 27709 USA. EM foster2@niehs.nih.gov NR 49 TC 48 Z9 50 U1 4 U2 20 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1040-8444 J9 CRIT REV TOXICOL JI Crit. Rev. Toxicol. PD OCT-NOV PY 2005 VL 35 IS 8-9 BP 713 EP 719 DI 10.1080/10408440591007395 PG 7 WC Toxicology SC Toxicology GA 993UH UT WOS:000233980100006 PM 16417038 ER PT J AU Vaidyanathan, J Vaidyanathan, TK Ramasubbu, N Ravichandran, S AF Vaidyanathan, J. Vaidyanathan, T. K. Ramasubbu, N. Ravichandran, S. TI A Computational and Experimental Analysis of Ligand Binding to Type 1 Collagen SO CURRENT COMPUTER-AIDED DRUG DESIGN LA English DT Article DE Docking simulation; ligand binding; collagen target; autodock; scoring ID DE-NOVO DESIGN; MOLECULAR-DYNAMICS SIMULATION; EMPIRICAL SCORING FUNCTIONS; DENOVO DRUG DESIGN; GENETIC ALGORITHM; AUTOMATED DOCKING; FLEXIBLE DOCKING; 3-DIMENSIONAL STRUCTURE; SEARCH ALGORITHMS; ENERGY FUNCTIONS AB Type 1 collagen is the primary protein in extracellular matrix of major tissues. Ligand binding to type 1 collagen is therefore an important problem of interest in areas such as adhesive bonding to tissues, mineralization of collagen scaffolds etc. The triple helical structure of collagen molecule, and the self-assembly of these molecules into fibrils as well as the role of water in its conformational state present interesting challenges in evaluating the binding of ligands to such a structure. Computer simulation of interactions between collagen and other molecular entities (e.g., ligands, proteins, mineral entities etc.) can provide a wealth of information. This paper reviews the computational methods suitable for applications to collagen-ligand binding studies and the current literature on such studies. These methods have been used for indirect (active analog approach) and direct (manual and automatic docking) methods of computer binding simulations. In particular, AutoDock method was extremely valuable to identify the low energy collagen-ligand complexes, to visualize the hydrogen bonds between collagen and ligands in their complexes, and to characterize the docking/binding energy parameters in the presence of water. Experimental binding assay studies were also used to characterize the interactions. The results give valuable information on criteria for formulation design in practical applications of adhesive bonding to tissues (e.g., bonding of dentin prior to filling of cavities to treat caries). Ongoing current studies also focus on immobilization of charged protein molecules on type 1 collagen to aid in biomimetic mineralization of collagen scaffolds. C1 [Vaidyanathan, J.; Vaidyanathan, T. K.; Ramasubbu, N.] Univ Med & Dent New Jersey, NJ Dent Sch, Newark, NJ 07103 USA. [Ravichandran, S.] NCI, Adv Biomed Comp Ctr, SAIC Frederick, Frederick, MD 21701 USA. RP Vaidyanathan, J (reprint author), Univ Med & Dent New Jersey, NJ Dent Sch, 110 Bergen St, Newark, NJ 07103 USA. EM jvaidyan@umdnj.edu FU National Institute of Dental and Craniofacial Research, National institutes of Health, Bethesda, MD, USA [1 R01 DE14370] FX Portions of this work were supported by grant #1 R01 DE14370 from the National Institute of Dental and Craniofacial Research, National institutes of Health, Bethesda, MD, USA. NR 136 TC 6 Z9 6 U1 3 U2 10 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1573-4099 J9 CURR COMPUT-AID DRUG JI Curr. Comput.-Aided Drug Des. PD OCT PY 2005 VL 1 IS 4 BP 397 EP 422 DI 10.2174/157340905774330264 PG 26 WC Chemistry, Medicinal; Computer Science, Interdisciplinary Applications SC Pharmacology & Pharmacy; Computer Science GA V17TF UT WOS:000207958800005 ER PT J AU Ramalingam, TR Reiman, RM Wynn, TA AF Ramalingam, TR Reiman, RM Wynn, TA TI Exploiting worm and allergy models to understand Th2 cytokine biology SO CURRENT OPINION IN ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Review DE allergy; asthma; IL-13; schistosomiasis; Th2 inflammation ID DENDRITIC CELL ACTIVATION; SCHISTOSOMA-MANSONI; RESPONSE DEVELOPMENT; NEMATODE INFECTION; TISSUE FIBROSIS; TRANSGENIC MICE; IN-VIVO; ASTHMA; INFLAMMATION; HELMINTH AB Purpose of review: Helminthic parasites and many allergens trigger highly polarized Th2-type immune responses. In most helminth infections, the Th2 response often leads to parasite expulsion or sequestration. During murine Schistosoma mansoni infection, however, the parasites persist and the chronic Th2 response induces severe pathological changes in the gut and liver. Thus, the study of schistosome infections in mice has become a popular model to study the pathogenesis of Th2 cytokine-mediated disease. This review will discuss recent findings from the schistosomiasis model that may be relevant to the understanding of allergic inflammation, asthma and Th2 cytokine biology in general. Recent findings: Evidence is accumulating that the Th2 pathway is not a 'default pathway' but one that is actively instructed by mechanisms that are only beginning to be understood. Other areas of intensive investigation include studies on alternatively activated macrophages, the role of dendritic cells in Th2 response development, the inhibitory function of IL-10, regulatory T-cells and decoy receptors on chronic Th2-mediated inflammation, and the role of chitinases in mediating Th2 disease. Finally, the development of novel eosinophil-deficient mice has also accelerated our understanding of the contribution of this important cell type to Th2 immunity. Summary: Many findings from the schistosomiasis model have been subsequently demonstrated in models of allergic disease, illustrating the utility of this model to dissect basic mechanisms of Th2-mediated inflammation. Further study of helminth-induced Th2 responses may expedite the discovery of new therapeutics for a wide range of Th2-associated diseases. C1 NIAID, NIH, Bethesda, MD 20892 USA. RP Wynn, TA (reprint author), 50 S Dr,Rm 6154,MSC 8003, Bethesda, MD 20892 USA. EM twynn@niaid.nih.gov RI Wynn, Thomas/C-2797-2011 NR 47 TC 27 Z9 27 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1528-4050 J9 CURR OPIN ALLERGY CL JI Curr. Opin. Allergy Clin. Immunol. PD OCT PY 2005 VL 5 IS 5 BP 392 EP 398 DI 10.1097/01.all.0000182542.30100.6f PG 7 WC Allergy; Immunology SC Allergy; Immunology GA 972LM UT WOS:000232455300003 PM 16131912 ER PT J AU Even-Ram, S Yamada, KM AF Even-Ram, S Yamada, KM TI Cell migration in 3D matrix SO CURRENT OPINION IN CELL BIOLOGY LA English DT Review ID EXTRACELLULAR-MATRIX; LANGERHANS CELLS; COLLAGEN MATRIX; IN-VIVO; INTEGRIN; SKIN; GELS; MT1-MMP; REQUIREMENTS; PROTEOLYSIS AB The ability of cells to migrate within the extracellular matrix and to remodel it depends as much on the physical and biochemical characteristics of a particular matrix as on cellular properties. Analyzing the different modes of migration of cells in matrices, and how cells switch between these modes, is vital for understanding a variety of physiological and pathological processes. Recent work provides new insights, but also raises some debates about the mechanisms and regulation of cell migration in three-dimensional matrices. C1 Natl Inst Dent & Craniofacial Res, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. RP Even-Ram, S (reprint author), Natl Inst Dent & Craniofacial Res, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. EM sram@dir.nidcr.nih.gov; kyamada@maii.nih.gov OI Even-Ram, Sharona/0000-0002-5540-3822; Yamada, Kenneth/0000-0003-1512-6805 NR 48 TC 278 Z9 283 U1 5 U2 36 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0955-0674 J9 CURR OPIN CELL BIOL JI Curr. Opin. Cell Biol. PD OCT PY 2005 VL 17 IS 5 BP 524 EP 532 DI 10.1016/j.ceb.2005.08.015 PG 9 WC Cell Biology SC Cell Biology GA 969HT UT WOS:000232225900012 PM 16112853 ER PT J AU Sartorelli, V Caretti, G AF Sartorelli, V Caretti, G TI Mechanisms underlying the transcriptional regulation of skeletal myogenesis SO CURRENT OPINION IN GENETICS & DEVELOPMENT LA English DT Review ID MUSCLE DIFFERENTIATION; GENE-EXPRESSION; HISTONE DEACETYLASES; MYOD; CELLS; ASSOCIATION; INHIBITION; P300; SIR2; POPULATION AB During skeletal myogenesis, chromatin-modifying enzymes are engaged at discrete genomic regions by transcription factors that recognize sequence-specific DNA motifs located at muscle gene regulatory regions. The composition of the chromatin-bound protein complexes and their temporally and spatially regulated recruitment influence gene expression. Recent findings are consistent with the concept that chromatin modifiers play an important role in regulating skeletal muscle gene expression and cellular differentiation. C1 NIAMSD, Muscle Gene Express Grp, Muscle Biol Lab, NIH, Bethesda, MD 20892 USA. RP Sartorelli, V (reprint author), NIAMSD, Muscle Gene Express Grp, Muscle Biol Lab, NIH, 50 South Dr,Room 1146, Bethesda, MD 20892 USA. EM sartorev@mail.nih.gov FU NIAMS NIH HHS [Z01 AR041126-06] NR 35 TC 92 Z9 98 U1 6 U2 14 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-437X J9 CURR OPIN GENET DEV JI Curr. Opin. Genet. Dev. PD OCT PY 2005 VL 15 IS 5 BP 528 EP 535 DI 10.1016/j.gde.2005.04.015 PG 8 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 972LB UT WOS:000232454200009 PM 16055324 ER PT J AU Hodes, RJ AF Hodes, RJ TI Aging and the immune system - Editorial overview SO CURRENT OPINION IN IMMUNOLOGY LA English DT Editorial Material C1 NIA, Bethesda, MD 20892 USA. RP Hodes, RJ (reprint author), NIA, Bldg 31,Room 5C27,31 Ctr Dr,Med Ctr Dr 2292, Bethesda, MD 20892 USA. EM hodesr@31.nia.nih.gov NR 0 TC 3 Z9 3 U1 0 U2 0 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 2005 VL 17 IS 5 BP 455 EP 456 DI 10.1016/j.coi.2005.07.006 PG 2 WC Immunology SC Immunology GA 964UF UT WOS:000231905800001 ER PT J AU Martin, MP Carrington, M AF Martin, MP Carrington, M TI Immunogenetics of viral infections SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID B-VIRUS-INFECTION; ANTIGEN CLASS-I; IMMUNOGLOBULIN-LIKE RECEPTOR; MHC CLASS-I; HEPATITIS-C; CERVICAL NEOPLASIA; HETEROZYGOTE ADVANTAGE; HIV-1 INFECTION; CYTOMEGALOVIRUS-INFECTION; COMPREHENSIVE ANALYSIS AB The HLA class I and II genes encode molecules that lie at the heart of the acquired immune response against infectious diseases. Associations between these polymorphic loci and genetically complex infectious diseases have been historically elusive, in contrast to the more obvious HLA associations with autoimmune diseases. High resolution molecular typing of large, clinically well-defined cohorts has begun to uncover evidence for the influence of HLA diversity on diseases of viral etiology, such as those caused by HIV-1, hepatitis B virus, hepatitis C virus and human papilloma virus. Combinations of HLA and KIR also appear to affect outcome to viral infection, supporting a role for HLA class I diversity in the innate immune response in addition to the acquired immune response. C1 Sci Applicat Int Corp, Basic Res Program, Frederick Inc, Lab Gen Divers,Natl Canc Inst, Frederick, MD 21702 USA. RP Carrington, M (reprint author), Sci Applicat Int Corp, Basic Res Program, Frederick Inc, Lab Gen Divers,Natl Canc Inst, POB B,Bldg 560,Room 21-98, Frederick, MD 21702 USA. EM carringt@ncifcrf.gov FU NCI NIH HHS [N01-CO-12400] NR 49 TC 75 Z9 78 U1 0 U2 6 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 2005 VL 17 IS 5 BP 510 EP 516 DI 10.1016/j.coi.2005.07.012 PG 7 WC Immunology SC Immunology GA 964UF UT WOS:000231905800011 PM 16084708 ER PT J AU Makarova, KS Koonin, EV AF Makarova, KS Koonin, EV TI Evolutionary and functional genomics of the Archaea SO CURRENT OPINION IN MICROBIOLOGY LA English DT Review ID TRANSFER-RNA SYNTHETASE; THERMOPHILIC ARCHAEA; NANOARCHAEUM-EQUITANS; CYSTEINE BIOSYNTHESIS; METHANOGENIC ARCHAEA; PROTEIN SEQUENCES; GENE; IDENTIFICATION; BACTERIA; EXOSOME AB In the past two years, archaeal genomics has achieved several breakthroughs. On the evolutionary front the most exciting development was the sequencing and analysis of the genome of Nanoarchaeum equitans, a tiny parasitic organism that has only similar to 540 genes. The genome of Nanoarchaeum shows signs of extreme rearrangement including the virtual absence of conserved operons and the presence of several split genes. Nanoarchaeum is distantly related to other archaea, and it has been proposed to represent a deep archaeal branch that is distinct from Euryarchaeota and Crenarchaeota. This would imply that many features of its gene repertoire and genome organization might be ancestral. However, additional genome analysis has provided a more conservative suggestion - that Nanoarchaeum is a highly derived euryarchaeon. Also there have been substantial developments in functional genomics, including the discovery of the elusive aminoacyl-tRNA synthetase that is involved in both the biosynthesis of cysteine and its incorporation into proteins in methanogens, and the first experimental validation of the predicted archaeal exosome. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Koonin, EV (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM koonin@ncbi.nlm.nih.gov FU Intramural NIH HHS NR 67 TC 34 Z9 39 U1 0 U2 5 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1369-5274 J9 CURR OPIN MICROBIOL JI Curr. Opin. Microbiol. PD OCT PY 2005 VL 8 IS 5 BP 586 EP 594 DI 10.1016/j.mib.2005.08.003 PG 9 WC Microbiology SC Microbiology GA 976OW UT WOS:000232744000014 PM 16111915 ER PT J AU Foroughi, S Thyagarajan, A Stone, KD AF Foroughi, S Thyagarajan, A Stone, KD TI Advances in pediatric asthma and atopic dermatitis SO CURRENT OPINION IN PEDIATRICS LA English DT Review DE allergic rhinitis; asthma; atopic dermatitis; corticosteroids ID INHALED BETA-AGONIST; METERED-DOSE INHALER; HOUSE-DUST MITE; FLUTICASONE PROPIONATE; PERSISTENT ASTHMA; AIR-POLLUTION; DOUBLE-BLIND; ENVIRONMENTAL INTERVENTION; COCKROACH ALLERGEN; YOUNG-CHILDREN AB Purpose of review Allergic diseases, including asthma, allergic rhinitis, atopic dermatitis, food allergy, and urticaria are common in general pediatric practice. This review highlights several significant advances in pediatric allergy over the past year, focusing on asthma and atopic dermatitis. Recent findings With increasing options for the treatment of allergic diseases much work is now focused on methods for individualizing treatments to a patients phenotype and genotype. Progress over the past year includes the characterization of effects of regular albuterol use in patients with genetic variations in the beta-adrenergic receptor. Maintenance asthma regiments for children in the first years of life are also an ongoing focus. The relation between upper airway allergic inflammation and asthma has continued to accumulate support and now extents to the middle ear. Environmental influences on asthma and interventions have been described, including environmental controls for asthma and the role of air pollution on lung development in children. Finally, concerns have been raised regarding the use of topical immunomodulators in young children with atopic dermatitis. Summary Progress continues in the care of children with atopic diseases. Attention to treatment with appropriate medications, patent-individualized environmental controls, and extensive education are the keys to successfully treating atopic children. This review highlights several recent advances but is not intended to be a comprehensive review. C1 Childrens Natl Med Ctr, Div Allergy Pulm & Sleep Med, Sect Allergy & Immunol, Washington, DC 20010 USA. NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. George Washington Univ, Sch Med & Hlth Sci, Dept Pediat, Washington, DC 20052 USA. RP Stone, KD (reprint author), Childrens Natl Med Ctr, Div Allergy Pulm & Sleep Med, Sect Allergy & Immunol, 111 Michigan Ave NW, Washington, DC 20010 USA. EM kstone@cnmc.org NR 44 TC 3 Z9 3 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1040-8703 J9 CURR OPIN PEDIATR JI CURR. OPIN. PEDIATR. PD OCT PY 2005 VL 17 IS 5 BP 658 EP 663 DI 10.1097/01.mop.0000178386.61932.0b PG 6 WC Pediatrics SC Pediatrics GA 964DB UT WOS:000231857800018 PM 16160544 ER PT J AU Bax, A Grishaev, A AF Bax, A Grishaev, A TI Weak alignment NMR: a hawk-eyed view of biomolecular structure SO CURRENT OPINION IN STRUCTURAL BIOLOGY LA English DT Review ID RESIDUAL DIPOLAR COUPLINGS; PROTEIN-STRUCTURE REFINEMENT; CHEMICAL-SHIFT ANISOTROPY; MALATE SYNTHASE-G; MEMBRANE-PROTEINS; NUCLEIC-ACIDS; PHOSPHOTRANSFERASE SYSTEM; POLYACRYLAMIDE-GELS; BIOLOGICAL MACROMOLECULES; ORIENTED PROTEINS AB Imposing a very slight deviation from the isotropic random distribution of macromolecules in solution in an NMR sample tube permits the measurement of residual internuclear dipolar couplings (RDCs). Such interactions are very sensitive functions of the time-averaged orientation of the corresponding internuclear vectors and thereby offer highly precise structural information. In recent years, advances have been made both in the technology to measure RDCs and in the computational procedures that integrate this information in the structure determination process. The exceptional precision with which RDCs can be measured under weakly aligned conditions is also starting to reveal the mostly, but not universally, subtle effects of internal protein dynamics. Importantly, RDCs potentially can reveal motions taking place on a timescale slower than rotational diffusion and analysis is uniquely sensitive to the direction of motion, not just its amplitude. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Bax, A (reprint author), NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. EM bax@nih.gov FU Intramural NIH HHS NR 61 TC 185 Z9 187 U1 2 U2 27 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 2005 VL 15 IS 5 BP 563 EP 570 DI 10.1016/j.sbi.2005.08.006 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 979MN UT WOS:000232946200012 PM 16140525 ER PT J AU Baggett, D Nakaya, MA McAuliffe, M Yamaguchi, TP Lockett, S AF Baggett, D Nakaya, MA McAuliffe, M Yamaguchi, TP Lockett, S TI Whole cell segmentation in solid tissue sections SO CYTOMETRY PART A LA English DT Article DE image segmentation; dynamic programming; image analysis; tissue analysis ID IMAGE SEGMENTATION; BREAST-CANCER; NUCLEI AB Background: Understanding the cellular and molecular basis of tissue development and function requires analysis of individual cells while in their tissue context. Methods: We developed software to find the optimum border around each cell (segmentation) from two-dimensional microscopic images of intact tissue. Samples were labeled with a fluorescent cell surface marker so that cell borders were brighter than elsewhere. The optimum border around each cell was defined as the border with an average intensity per unit length greater that any other possible border around that cell, and was calculated using the gray-weighted distance transform. Algorithm initiation requiring the user to mark two points per cell, one approximately in the center and the other on the border, ensured virtually 100% correct segmentation. Thereafter segmentation was automatic. Results: The method was highly robust, because intermittent labeling of the cell borders, diffuse borders, and spurious signals away from the border do not significantly affect the optimum path. Computer-generated cells with increasing levels of added noise showed that the approach was accurate provided the cell could be detected visually. Conclusions: We have developed a highly robust algorithm for segmenting images of surface-labeled cells, enabling accurate and quantitative analysis of individual cells in tissue. (c) 2005 International society for Analytical Cytology. C1 Natl Canc Inst, Image Anal Lab, SAIC Frederick, Frederick, MD 21702 USA. Worcester Polytech Inst, Worcester, MA 01609 USA. NCI, Canc & Dev Biol Lab, Ctr Canc Res, NIH, Frederick, MD 21701 USA. NIH, Ctr Image Anal, Bethesda, MD 20892 USA. RP Lockett, S (reprint author), Natl Canc Inst, Image Anal Lab, SAIC Frederick, Room 104A,B538, Frederick, MD 21702 USA. EM slockett@ncifcrf.gov FU NCI NIH HHS [N01-CO56000] NR 25 TC 48 Z9 50 U1 1 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1552-4922 J9 CYTOM PART A JI Cytom. Part A PD OCT PY 2005 VL 67A IS 2 BP 137 EP 143 DI 10.1002/cyto.a.20162 PG 7 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 970IT UT WOS:000232299300013 PM 16163696 ER PT J AU Verheyden, JM Lewandoski, M Deng, CX Harfe, BD Sun, X AF Verheyden, JM Lewandoski, M Deng, CX Harfe, BD Sun, X TI Conditional inactivation of Fgfr1 in mouse defines its role in limb bud establishment, outgrowth and digit patterning SO DEVELOPMENT LA English DT Article DE Cre-mediated recombination; FGF; Fgfr1 signaling; limb development; mouse; patterning; Shh AB Previous studies have implicated fibroblast growth factor receptor 1 (FGFR1) in limb development. However, the precise nature and complexity of its role have not been defined. Here, we dissect Fgfr1 function in mouse limb by conditional inactivation of Fgfr1 using two different Cre recombinase-expressing lines. Use of the T (brachyury)-cre line led to Fgfr1 inactivation in all limb bud mesenchyme (LBM) cells during limb initiation. This mutant reveals FGFR1 function in two phases of limb development. In a nascent limb bud, FGFR1 promotes the length of the proximodistal (PD) axis while restricting the dimensions of the other two axes. It also serves an unexpected role in limiting LBM cell number in this early phase. Later on during limb outgrowth, FGFR1 is essential for the expansion of skeletal precursor population by maintaining cell survival. Use of mice carrying the sonic hedgehog(cre) (Shh(cre)) allele led to Fgfr1 inactivation in posterior LBM cells. This mutant allows us to test the role of Fgfr1 in gene expression regulation without disturbing limb bud growth. Our data show that during autopod patterning, FGFR1 influences digit number and identity, probably through cell-autonomous regulation of Shh expression. Our study of these two Fgfr1 conditional mutants has elucidated the multiple roles of FGFR1 in limb bud establishment, growth and patterning. C1 Univ Wisconsin, Genet Lab, Madison, WI 53706 USA. Natl Canc Inst, Canc & Dev Biol Lab, Frederick Canc Res & Dev Ctr, Ft Detrick, MD 21702 USA. NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. Univ Florida, Coll Med, Dept Mol Genet & Microbiol, Gainesville, FL 32610 USA. RP Sun, X (reprint author), Univ Wisconsin, Genet Lab, 425G Henry Mall, Madison, WI 53706 USA. EM xsun@wisc.edu RI deng, chuxia/N-6713-2016 FU NICHD NIH HHS [R01 HD045522]; NIGMS NIH HHS [5T32GM07133] NR 60 TC 58 Z9 58 U1 0 U2 2 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD OCT PY 2005 VL 132 IS 19 BP 4235 EP 4245 DI 10.1242/dev.02001 PG 11 WC Developmental Biology SC Developmental Biology GA 980MP UT WOS:000233022900004 PM 16120640 ER PT J AU Mermall, V Bonafe, N Jones, L Sellers, JR Cooley, L Mooseker, MS AF Mermall, V Bonafe, N Jones, L Sellers, JR Cooley, L Mooseker, MS TI Drosophila myosin V is required for larval development and spermatid individualization SO DEVELOPMENTAL BIOLOGY LA English DT Article DE actin; microtubules; investment cones; individualization complex; gut; oogenesis; CNS ID SITE-SPECIFIC RECOMBINATION; SACCHAROMYCES-CEREVISIAE; UNCONVENTIONAL MYOSIN; GENETIC-ANALYSIS; MITOTIC SPINDLE; ACTIN-FILAMENTS; 2ND CHROMOSOME; MESSENGER-RNA; BUDDING YEAST; LINKS RAB27A AB Class V myosins are multifunctional molecular motors implicated in vesicular traffic, RNA transport, and mcchanochernical coupling of the actin and microtubule-based cytoskeletons. To assess the function of the single myosin V gene in Drosophila (MyoV), we have characterized both deletion and truncation alleles. Mutant animals exhibit no detectable defects during embryogenesis but are delayed in larval development; most die prior to 3rd instar. MyoV protein is widely distributed; however, there are no obvious cytological defects in mutant larval tissues where MyoV was normally highly expressed. Of the few adult MyoV mutant escapers, females were fertile but males were not. We examined the expression of MyoV during spermatogenesis. MyoV was associated with membranes, microtubule, and actin structures required for spermatid maturation; MyoV was strongly associated with the sperm nuclei during the maturation of the actin-rich investment cones that package spermatids in individual membranes. In MyoV mutant escaper males, the early stages of spermatogenesis were normal; however, in the later stages, the investment cones stained weakly for actin and their registration was disrupted; no mature sperm were produced. Our results suggest that MyoV contributes to the formation of the actin-based investment cones and acts to coordinate and/or anchor these structures and other components of the individualization complex. (c) 2005 Elsevier Inc. All rights reserved. C1 Yale Univ, Sch Med, Dept Genet, New Haven, CT 06520 USA. Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT 06510 USA. Yale Univ, Sch Med, Dept Cell Biol, New Haven, CT 06520 USA. Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06520 USA. NHLBI, NIH, Bethesda, MD 20892 USA. RP Cooley, L (reprint author), Yale Univ, Sch Med, Dept Genet, New Haven, CT 06520 USA. EM lynn.cooley@yale.edu FU NIDDK NIH HHS [DK-25387, DK-55389]; NIGMS NIH HHS [GM43301, R01 GM043301] NR 78 TC 23 Z9 24 U1 1 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD OCT 1 PY 2005 VL 286 IS 1 BP 238 EP 255 DI 10.1016/j.ydbio.2005.07.028 PG 18 WC Developmental Biology SC Developmental Biology GA 974FD UT WOS:000232575800019 PM 16126191 ER PT J AU Shaffer, KL Sharma, A Snapp, EL Hegde, RS AF Shaffer, KL Sharma, A Snapp, EL Hegde, RS TI Regulation of protein compartmentalization expands the diversity of protein function SO DEVELOPMENTAL CELL LA English DT Article ID ENDOPLASMIC-RETICULUM MEMBRANE; SIGNAL SEQUENCE RECOGNITION; PRION PROTEIN; GLUCOCORTICOID-RECEPTOR; TRANSLOCATION CHANNEL; GENE-EXPRESSION; ER MEMBRANE; CALRETICULIN; PEPTIDE; MODULATION AB Proteins destined for the secretory pathway are translocated into the endoplasmic reticulum (ER) by signal sequences that vary widely in their functional properties. We have investigated whether differences in signal sequence function have been exploited for cellular benefit. A cytosolic form of the ER chaperone calreticulin was found to arise by an aborted translocation mechanism dependent on its signal sequence and factors in the ER lumen and membrane. A signal sequence that functions independently of these accessory translocation factors selectively eliminated cytosolic calreticulin. In vivo replacement of endogenous calreticulin with a constitutively translocated form influenced glucocorticoid receptor-mediated gene activation without compromising chaperone activity in the ER. Thus, in addition to its well-established ER lumenal functions, calreticulin has an independent role in the cytosol that depends critically on its inefficient compartmentalization. We propose that regulation of protein translocation represents a potentially general mechanism for generating diversity of protein function. C1 NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Hegde, RS (reprint author), NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. EM hegder@mail.nih.gov OI Hegde, Ramanujan/0000-0001-8338-852X FU Intramural NIH HHS NR 40 TC 64 Z9 65 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD OCT PY 2005 VL 9 IS 4 BP 545 EP 554 DI 10.1016/j.devcel.2005.09.001 PG 10 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 974UL UT WOS:000232616800013 PM 16198296 ER PT J AU Engeli, S Bohnke, J Feldpausch, M Gorzelniak, K Janke, J Batkai, S Pacher, P Harvey-White, J Luft, FC Sharma, AM Jordan, J AF Engeli, S Bohnke, J Feldpausch, M Gorzelniak, K Janke, J Batkai, S Pacher, P Harvey-White, J Luft, FC Sharma, AM Jordan, J TI Activation of the peripheral endocannabinoid system in human obesity SO DIABETES LA English DT Article ID ENDOGENOUS CANNABINOID SYSTEM; CARDIOVASCULAR RISK; CB1 RECEPTORS; FOOD-INTAKE; ANANDAMIDE; OVERWEIGHT; APPETITE; RATS; MICE; PHARMACOLOGY AB Obesity is the main risk factor for the development of type 2 diabetes. Activation of the central endocannabinoid system increases food intake and promotes weight gain. Blockade of the cannabinoid type 1 (CB-1) receptor reduces body weight in animals by central and peripheral actions; the role of the peripheral endocannabinoid system in human obesity is now being extensively investigated. We measured circulating endocannabinoid concentrations and studied the expression of CB-1 and the main degrading enzyme, fatty acid amide hydrolase (FAAH), in adipose tissue of lean (n = 20) and obese (n = 20) women and after a 5% weight loss in a second group of women (n = 17). Circulating levels of anandamide and 1/2-arachidonoylglycerol were increased by 35 and 52% in obese compared with lean women (P < 0.05). Adipose tissue mRNA levels were reduced by -34% for CB-1 and -59% for FAAH in obese subjects (P < 0.05). A strong negative correlation was found between FAAH expression in adipose tissue and circulating endocannabinoids. Circulating endocannabinoids and CB-1 or FAAH expression were not affected by 5% weight loss. The expression of CB-1 and FAAH was increased in mature human adipocytes compared with in preadipocytes and was found in several human tissues. Our findings support the presence of a peripheral endocannabinoid system that is upregulated in human obesity. C1 Volhard Clin Res Ctr, D-13125 Berlin, Germany. HELIOS Klinikum, Berlin, Germany. NIAAA, Lab Physiol Studies, NIH, Bethesda, MD USA. McMaster Univ, Dept Med, Hamilton, ON, Canada. RP Engeli, S (reprint author), Volhard Clin Res Ctr, Charite Campus Buch,Wiltberg Str 50, D-13125 Berlin, Germany. EM engeli@fvk.charite-buch.de RI Batkai, Sandor/G-3889-2010; Pacher, Pal/B-6378-2008; Batkai, Sandor/H-7983-2014; OI Pacher, Pal/0000-0001-7036-8108; Luft, Friedrich/0000-0002-8635-1199 FU Intramural NIH HHS [Z01 AA000375-02] NR 37 TC 385 Z9 400 U1 1 U2 11 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 2005 VL 54 IS 10 BP 2838 EP 2843 DI 10.2337/diabetes.54.10.2838 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 969MD UT WOS:000232237400002 PM 16186383 ER PT J AU Muller, YHL Infante, AM Hanson, RL Love-Gregory, L Knowler, W Bogardus, C Baier, LJ AF Muller, YHL Infante, AM Hanson, RL Love-Gregory, L Knowler, W Bogardus, C Baier, LJ TI Variants in hepatocyte nuclear factor 4 alpha are modestly associated with type 2 diabetes in Pima Indians SO DIABETES LA English DT Article ID AUTOSOMAL GENOMIC SCAN; CHROMOSOME 20Q; TRANSCRIPTION FACTORS; SUSCEPTIBILITY LOCUS; FACTOR-4-ALPHA GENE; INSULIN-RESISTANCE; UPSTREAM PROMOTER; SIB PAIRS; LINKAGE; POPULATION AB Single nucleotide polymorphisms (SNPs) within the hepatocyte nuclear factor 4 alpha (HNF4 alpha) gene are associated with type 2 diabetes in Finns and Ashkenazi Jews. Previous studies in both populations have reported linkage to type 2 diabetes near the HNF4 alpha locus on chromosome 20q12-13. To investigate whether HNF4 alpha is a diabetes susceptibility gene in Pima Indians, a population with the highest reported prevalence of type 2 diabetes but with no evidence for linkage of the disease on chromosome 20q, 19 SNPs across the promoter and coding region of HNF4 alpha were genotyed for association analysis. In a group of 1,031 Pima Indians (573 diabetic and 464 nondiabetic subjects), three SNPs in HNF4 alpha (rs3212183 and rs2071197 located in introns 3 and 1, respectively, and rs6031558, an extremely rare SNP located in the P2 promoter region) were modestly associated with type 2 diabetes (rs3212183 odds-ratio [OR] 1.34 [95% CI 1.07-1.67], P = 0.009; rs2071197 1.34 [1.07- 1.66], P = 0.008; and rs6031558 3.18 [1.03-9.84], P = 0.04, adjusted for age, sex, birth year,heritage, and family membership). We conclude that variants in HNF4 alpha do not appear to be major determinants for type 2 diabetes in Pima Indians; however, HNF4 alpha may have a minor role in type 2 diabetes susceptibility within this Native American population. C1 NIDDKD, Clin Diabet & Nutr Sect, NIH, Phoenix Epidemiol & Clin Res Branch, Phoenix, AZ 85016 USA. Washington Univ, Sch Med, St Louis, MO USA. RP Baier, LJ (reprint author), NIDDKD, Clin Diabet & Nutr Sect, NIH, Phoenix Epidemiol & Clin Res Branch, 4212 N 16Th St, Phoenix, AZ 85016 USA. EM lbaier@phx.niddk.nih.gov RI Hanson, Robert/O-3238-2015 OI Hanson, Robert/0000-0002-4252-7068 FU NIDDK NIH HHS [Z01 DK069072-08] NR 22 TC 33 Z9 35 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 2005 VL 54 IS 10 BP 3035 EP 3039 DI 10.2337/diabetes.54.10.3035 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 969MD UT WOS:000232237400030 PM 16186411 ER PT J AU Fox, CS Larson, MG Leip, EP Meigs, JB Wilson, PWF Levy, D AF Fox, CS Larson, MG Leip, EP Meigs, JB Wilson, PWF Levy, D TI Glycemic status and development of kidney disease - The Framingham Heart Study SO DIABETES CARE LA English DT Article; Proceedings Paper CT 44th Annual American-Heart-Association Conference on Cardiovascular Disease Epidemiology and Prevention CY MAR 05, 2004 CL San Francisco, CA SP Amer Heart Assoc ID GLOMERULAR-FILTRATION-RATE; CARDIOVASCULAR OUTCOMES; DIABETES-MELLITUS; RENAL-INSUFFICIENCY; RISK-FACTOR; INSULIN-RESISTANCE; SERUM CREATININE; COMMUNITY; POPULATION; ADULTS AB OBJECTIVE - Diabetes is a major risk factor for the development of kidney disease and is the leading cause of end-stage renal disease in the U.S. Whether pre-diabetes is associated with the development of kidney disease is unclear. RESEARCH DESIGN AND METHODS - Subjects free of chronic kidney disease (CKD) were drawn from the Framingham Heart Study offspring cohort (1991-1995), given an oral glucose tolerance test, and followed for an average of 7 years for development of CKD (glomerular filtration rate [GFR] of < 59 ml/min per 1.73 m(2) in women and < 64 ml/min per 1.73 m(2) in men). Multivariable logistic regression models, adjusted for cardiovascular disease risk factors including age, sex, hypertension, smoking, BMI, total and HDL cholesterol levels, and prevalent myocardial infarction or congestive heart failure, were used to estimate the odds of patients developing kidney disease among glycemic categories. RESULTS - Of 2,398 subjects (53% women; mean age 54 years), 63% were normoglycemic, 29% had impaired fasting glucose (IFG) or impaired glucose tolerance (IGT), 3.4% were newly diabetic, and 4.6% had known diabetes. By glycemic category, mean GFR at follow-up was 87, 85, 82, and 78 ml/min per 1.73 m(2), respectively. The fully adjusted odds of developing CKD were 0.98 (95% CI 0.67-1.45), 1.71 (95% CI 0.83-3.55), and 1.93 (95% CI 1.06-3.49) among those with IFG or IGT, newly diagnosed diabetes, or known diabetes, respectively, compared with those who were normoglycemic at baseline. Among participants without diabetes, metabolic syndrome was not associated with kidney disease at follow-up (odds ratio 1.46, P = 0. 06). CONCLUSIONS - Cardiovascular disease risk factors explain much of the relationship between prediabetes and the development of chronic kidney disease. Clinical trials are warranted to determine whether vascular risk factor modification can slow the decline of kidney function among those with pre-diabetes. C1 NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. NHLBI, NIH, Bethesda, MD 20892 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Massachusetts Gen Hosp, Dept Med, Gen Med Div, Boston, MA 02114 USA. RP Fox, CS (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayne Ave,Suite 2, Framingham, MA 01702 USA. EM foxca@nhlbi.nih.gov FU NHLBI NIH HHS [N01-HC-25195] NR 32 TC 108 Z9 114 U1 0 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD OCT PY 2005 VL 28 IS 10 BP 2436 EP 2440 DI 10.2337/diacare.28.10.2436 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 971CO UT WOS:000232358900016 PM 16186276 ER PT J AU Nalbandian, A Pang, ALY Rennert, OM Chan, WY Ravindranath, N Djakiew, D AF Nalbandian, A Pang, ALY Rennert, OM Chan, WY Ravindranath, N Djakiew, D TI A novel function of differentiation revealed by cDNA microarray profiling of p75(NTR)-regulated gene expression SO DIFFERENTIATION LA English DT Article DE tumor suppressor gene; gene expression profile; cDNA microarray; PC-3 prostate tumor cells; p75 neurotrophin receptor; quantitative real-time polymerase chain reaction; retinoic acid ID NERVE GROWTH-FACTOR; HUMAN PROSTATE-CANCER; RETINOIC ACID RECEPTORS; PLASMINOGEN-ACTIVATOR; PROMYELOCYTIC LEUKEMIA; SIGNAL-TRANSDUCTION; INDUCED APOPTOSIS; CELL-LINES; X-RECEPTOR; IN-VIVO AB The expression of the p75 neurotrophin receptor (p75(NTR)) is diminished in epithelial cells during progression of prostate cancer in vivo and in vitro. Previous studies have demonstrated a role for p75(NTR) as a tumor suppressor in prostate growth. To better understand the molecular mechanism of p75(NTR) on tumor suppression, we utilized a complementary deoxyribonucleic acid microarray composed of similar to 6,000 human cancer-related genes to determine the gene expression pattern altered by re-introduction of p75(NTR) into PC-3 prostate tumor cells. Comparison of the transcripts in the neo and p75(NTR)-transfected cells revealed 52 differentially expressed genes, of which 21 were up-regulated and 31 were down-regulated in the presence of p75(NTR). Based on the known biological functions of the p75(NTR)-regulated genes, we observed that p75(NTR) modulated the expression of genes that are critically involved in the regulation of differentiation as well as cell adhesion, signal transduction, apoptosis, tumor cell invasion, and metastasis. Several differentially expressed genes identified by microarray were selected for confirmation using quantitative real-time polymerase chain reaction. Immunoblot analysis further confirmed increased cellular retinoic acid-binding protein I (CRABPI) and IGFBP5 protein levels and decreased level of PLAUR protein with increasing p75(NTR) protein expression. As CRABPI was elevated far more than any other genes, we observed that the retinoids, all-trans retinoic acid and 9-cis retinoic acid, that bind CRABPI, promoted nitroblue tetrazolium-associated functional cell differentiation in p75(NTR) PC-3 cells, but not in neo control PC-3 cells. Subsequent examination of the retinoic acid receptors (RARs) expression levels demonstrated an absence of RAR-beta in the neo control cells and re-expression in the p75(NTR) expressing cells, consistent with previous findings where RAR-beta is believed to play a critical role as a tumor suppressor gene that is lost during de-differentiation of prostate epithelial cells. Whereas the RAR-alpha and -gamma protein levels remained unchanged, retinoid X receptor (RXR)-alpha and -beta also exhibited increasing protein levels with re-expression of the p75(NTR) protein. Moreover, the ability of p75(NTR) siRNA to knockdown levels of RAR-beta, RXR-alpha, and RXR-beta supports the specificity of the functional involvement of p75(NTR) in differentiation. Hence, re-expression of the p75(NTR) appears to partially reverse de-differentiation of prostate cancer cells by up-regulating the expression of CRABPI for localized sequestration of retinoids that are available to newly up-regulated RAR-beta, RXR-alpha, and RXR-beta. C1 Georgetown Univ, Med Ctr, Dept Cell Biol, Washington, DC 20057 USA. NICHHD, Sect Dev Genom, Lab Clin Genom, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. Georgetown Univ, Med Ctr, Vincent T Lombardi Comprehens Canc Ctr, Washington, DC 20057 USA. RP Djakiew, D (reprint author), Georgetown Univ, Med Ctr, Dept Cell Biol, Med Dent Bldg,SE 220,3900 Reservoir Rd NW, Washington, DC 20057 USA. EM djakiewd@georgetown.edu FU NIDDK NIH HHS [R01 DK52626] NR 68 TC 12 Z9 14 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0301-4681 J9 DIFFERENTIATION JI Differentiation PD OCT PY 2005 VL 73 IS 8 BP 385 EP 396 DI 10.1111/j.1432-0436.2005.00040.x PG 12 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 987IY UT WOS:000233512800001 PM 16316409 ER PT J AU Hussain, SZ Strom, SC Kirby, MR Burns, S Langemeijer, S Ueda, T Hsieh, M Tisdale, JF AF Hussain, SZ Strom, SC Kirby, MR Burns, S Langemeijer, S Ueda, T Hsieh, M Tisdale, JF TI Side population cells derived from adult human liver generate hepatocyte-like cells in vitro SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE human; side population; stem cells; hepatic; CD45 ID HEMATOPOIETIC STEM-CELLS; DIFFERENTIATION; EXPRESSION; REGENERATION; FUSION; VIVO; TUMORS; CD34; RAT AB We sought to determine whether hepatic side population (SP) cells derived from adult human liver possess the potential of a novel candidate hepatic stem cell. Human cadaveric donor liver was subjected to collagenase perfusion and hepatocytes were separated from nonparenchymal cells by differential centrifugation. SP cells were isolated from the nonparenchymal portion after Hoechst 33342 staining. Since CD45 is a panleukocyte antigen, CD45-negative SP cells were separated from the vast majority of CD45-positive SP cells (90%), and hepatic growth medium was used to culture both groups. Both CD45-negative and CD45-positive hepatic SP cells generated colonies in the hepatic growth medium in 2-3 weeks. The colonies yielded large cells morphologically consistent with human hepatocytes, demonstrating granule-rich cytoplasm, dense, often double nuclei, and intracellular lipofuscin pigment. The cultured cells from both sources were positive for markers of human hepatocytes: HepPar, cytokeratin 8 (CK8), and human albumin. Reverse transcriptase-polymerase chain reaction (RT-PCR) performed on both groups demonstrated positivity for additional liver markers including human albumin, CK18, alpha-1 anti-trypsin, and the human cytochrome P450 enzyme CYP2B6. Double immunostaining (CD45 and HepPar) and RT-PCR confirmed that the hepatocyte-like cells derived from the CD45-negative SP cells acquired HepPar positivity but had no detectable CD45 antigen expression. In contrast, the cultured cells derived from the CD45-positive SP cells also acquired HepPar positivity, but only a minimal fraction expressed the CD45 antigen. We conclude that hepatic SP cells derived from the nonparenchymal portion of human liver are a potential source of human hepatocytes irrespective of their CD45 status, and further animal studies will be required to assess their regenerative potential. C1 NIDDK, Mol & Clin Hematol Branch, Nihon Univ, Bethesda, MD USA. Childrens Natl Med Ctr, Div Gastroenterol, Washington, DC 20010 USA. Univ Pittsburgh, Dept Pathol, Pittsburgh, PA 15260 USA. NHGRI, NIH, Bethesda, MD 20892 USA. RP Tisdale, JF (reprint author), NIDDK, Mol & Clin Hematol Branch, Nihon Univ, Bethesda, MD USA. EM Johntis@intra.niddk.nih.gov OI Strom, Stephen/0000-0002-2889-3387 FU Intramural NIH HHS [Z01 DK027012-04] NR 33 TC 46 Z9 47 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD OCT PY 2005 VL 50 IS 10 BP 1755 EP 1763 DI 10.1007/s10620-005-2933-x PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 968KS UT WOS:000232162000001 PM 16187169 ER PT J AU Ridenour, TA Maldonado-Molina, M Compton, WM Spitznagel, EL Cottler, LB AF Ridenour, TA Maldonado-Molina, M Compton, WM Spitznagel, EL Cottler, LB TI Factors associated with the transition from abuse to dependence among substance abusers: Implications for a measure of addictive liability SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE abuse; dependence; abuse liability; etiology ID DSM-IV ALCOHOL; USE DISORDER CRITERIA; DRUG-USE; FAMILIAL TRANSMISSION; RHESUS-MONKEYS; AUDADIS-ADR; COCAINE; RELIABILITY; DIAGNOSES; HUMANS AB This study was conducted to test the validity of a measure that has potential to bridge research on the addictive liability of drugs and on individuals' liability to addiction, which to date have evolved in largely parallel arenas. The length of time between onset of abuse and dependence (LOTAD) has evolved from recent findings on transitions through levels of addiction; it was hypothesized that shorter LOTAD is indicative of greater addictive liability. Hypotheses were based on animal studies and human studies. Retrospective data from the DSM-IV Substance Use Disorders Work Group were reanalyzed using configural frequency analysis, survival curves, bivariate Kendall's tau associations, and linear regression. The sample consisted of participants recruited from community and clinical settings. The measure was the Composite International Diagnostic Interview-Substance Abuse Module (CIDI-SAM). The shortest LOTADs were observed for disorders related to use of cocaine and opiates, followed by cannabis and then alcohol regardless of the subsample that was analyzed. As hypothesized, females and early initiators of drug use had shorter LOTADs compared to men and other initiators of drug use; no consistent differences in LOTAD were observed between African-Americans and Caucasians. None of the LOTAD variance associated with differences between drugs could be accounted for by gender, early use of the drug, or ethnicity. Specific areas of research where LOTAD might be useful as well as how LOTAD might be improved are discussed. (c) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Penn State Univ, Prevent Res Ctr, State Coll, PA 16801 USA. NIDA, Bethesda, MD 20892 USA. Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. RP Ridenour, TA (reprint author), Penn State Univ, Prevent Res Ctr, 135 E Nittany Ave,Ste 402, State Coll, PA 16801 USA. EM tar13@psu.edu RI Maldonado-Molina, Mildred/A-5272-2008; OI Ridenour, Ty/0000-0002-9709-6808 FU NIAAA NIH HHS [AA12111, R01 AA012111]; NIDA NIH HHS [DA00430, DA15984, K01 DA000430, K01 DA000434, R01 DA015984, Z01 DA000434]; NIMH NIH HHS [MH17104, T32 MH017104] NR 51 TC 43 Z9 45 U1 6 U2 11 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD OCT 1 PY 2005 VL 80 IS 1 BP 1 EP 14 DI 10.1016/j.drugalcdep.2005.02.005 PG 14 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 969KT UT WOS:000232233700001 PM 16157227 ER PT J AU Schroeder, JR Schmittner, JP Epstein, DH Preston, KL AF Schroeder, JR Schmittner, JP Epstein, DH Preston, KL TI Adverse events among patients in a behavioral treatment trial for heroin and cocaine dependence: Effects of age, race, and gender SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE substance dependence; clinical trials; safety monitoring ID ANTIRETROVIRAL THERAPY; DRUG-USERS; ALCOHOL; DISORDERS AB Safety monitoring is a critical element of clinical trials evaluating treatment for substance dependence, but is complicated by participants' high levels of medical and psychiatric comorbidity. This paper describes AEs reported in a large (N = 286), 29-week outpatient study of behavioral interventions for heroin and cocaine dependence in methadone-maintained outpatients. A total of 884 AEs were reported (3.1 per patient, 0.12 per patient-week), the most common being infections (26.8%), gastrointestinal (20.5%), musculoskeletal (12.3%), and general (10%) disorders. Serious AEs were uncommon (1.6% of total). Female participants reported significantly higher rates of AEs (incidence density ratio, IDR = 1.38, p < 0.0001); lower rates of AEs were reported by African Americans (IDR = 0.73, p < 0.0001) and participants over age 40 reported lower rates of AEs (IDR = 0.84, p = 0.0095). AE incidence was not associated with the study intervention or with psychiatric comorbidity. Further work is needed to adapt AE coding systems for behavioral trials for substance dependence; the standard Medical Dictionary for Regulatory Activities, International Federation of Pharmaceutical Manufacturers Associations (MedDRA) coding system used in this report did not contain a separate category for one of the most common types of AE, dental problems. Nonetheless, the data reported here should help provide a context in which investigators and IRBs can interpret the patterns of AEs they encounter. (c) 2005 Elsevier Ireland Ltd. All rights reserved. C1 NIDA, Intramural Res Program, Baltimore, MD 21224 USA. RP Schroeder, JR (reprint author), NIDA, Intramural Res Program, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM jschroed@intra.nida.nih.gov RI Preston, Kenzie/J-5830-2013 OI Preston, Kenzie/0000-0003-0603-2479 FU Intramural NIH HHS NR 17 TC 6 Z9 6 U1 1 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD OCT 1 PY 2005 VL 80 IS 1 BP 45 EP 51 DI 10.1016/j.drugalcdep.2005.03.007 PG 7 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 969KT UT WOS:000232233700005 PM 16157230 ER PT J AU Stinson, FS Grant, BE Dawson, DA Ruan, WJ Huang, B Saha, T AF Stinson, FS Grant, BE Dawson, DA Ruan, WJ Huang, B Saha, T TI Comorbidity between DSM-IV alcohol and specific drug use disorders in the United States: Results from the national epidemiologic survey on alcohol and related conditions SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE DSM-IV alcohol abuse; DSM-IV alcohol dependence; epidemiology; comorbidity ID INTERVIEW SCHEDULE AUDADIS; GENERAL-POPULATION SAMPLE; SUBSTANCE USE DISORDERS; III-R; MENTAL-HEALTH; PSYCHIATRIC-DISORDERS; NOSOLOGICAL COMPARISONS; 12-MONTH PREVALENCE; ANXIETY DISORDERS; ABUSE DIAGNOSES AB Background: To date, there have been no published data on 12-month comorbidity of DSM-IV alcohol and drug use disorders in the general U.S. population. The purposes of the present study were to examine the prevalence and comorbidity of alcohol and specific drug use disorders, and to identify sociodemographic and psychopathologic correlates and treatment seeking among three groups of respondents: (1) those with alcohol use disorders only; (2) those with drug use disorders only; (3) those with comorbid alcohol and drug use disorders. Methods: Information on 12-month alcohol and specific drug use disorders in the United States was derived from face-to-face interviews in the National Institute on Alcohol Abuse and Alcoholism's (NIAAA) 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC: n = 43,093). Results: Prevalences were 7.35% for alcohol use disorders only, 0.90% for drug use disorder only and 1.10% for comorbid alcohol and drug use disorders. Sociodemographic and psychopathologic correlates of these three groups were quite different, with the drug use disorder and comorbid groups significantly more likely to be young, male, never married and of lower socioeconomic status than the alcohol use disorder only group. Associations between current alcohol use disorders and 25 specific drug use disorders were generally positive and statistically significant. The 12-month prevalence of treatment seeking significantly increased from 6.06% for those with an alcohol use disorder only to 15.63% for those with a drug use disorder only, and to 21.76% for those with comorbid alcohol and drug use disorders. Conclusions: This study provides detailed data on the homotypic comorbidity of alcohol use disorders and 25 different drug use disorders and confirms the high levels of association seen in previous studies based on lifetime measures. Implications of this study are discussed in terms of integrating alcohol and drug treatment services and refining prevention and intervention efforts. Published by Elsevier Ireland Ltd. C1 NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Stinson, FS (reprint author), NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH,Dept Hlth & Human Serv, Room 3075,MS 9304,5635 Fishers Lane, Bethesda, MD 20892 USA. EM fstinson@mail.nih.gov NR 44 TC 228 Z9 232 U1 4 U2 17 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD OCT 1 PY 2005 VL 80 IS 1 BP 105 EP 116 DI 10.1016/j.drugalcdep.2005.03.009 PG 12 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 969KT UT WOS:000232233700010 PM 16157233 ER PT J AU Hasin, DS Hatzenbueler, M Smith, S Grant, BE AF Hasin, DS Hatzenbueler, M Smith, S Grant, BE TI Co-occurring DSM-IV drug abuse in DSM-IV drug dependence: Results from the National Epidemiologic Survey on Alcohol and Related Conditions SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE alcohol abuse; drug abuse; alcohol dependence; drug dependence ID INTERVIEW SCHEDULE AUDADIS; SUBSTANCE USE DISORDERS; GENERAL-POPULATION SAMPLE; ICD-10 ALCOHOL; HEAVY DRINKERS; PRIMARY-CARE; PRIME-MD; III-R; DIAGNOSES; RELIABILITY AB The extent to which dependence occurs with or without abuse is important because of the potential for underestimation and biased estimates of drug dependence in surveys that rely on abuse as a screening method for dependence. The purpose of this paper was to present the prevalence of DSM-IV drug dependence with and without drug abuse in a nationally representative sample, as well as in subgroups defined by sex, age and race/ethnicity. Among all respondents with current drug dependence, 22.0% did not additionally meet criteria for abuse (19.5% among males and 27.8% among females). Current drug dependence without abuse was especially common among females age 45-64 (52.6% of all cases). Among those with lifetime diagnoses of drug dependence, a small proportion overall, 5.0% had no symptoms of abuse, with the highest proportion again found among females aged 45-64 (19.5% of all cases). The use of drug abuse as a screening method for drug dependence in large epidemiologic studies will differentially underestimate the prevalence of dependence by subgroup, affecting many types of research. Dependence with and without abuse may represent heterogeneous phenotypes for genetic and gene-environment research, which should be explored. (c) 2005 Elsevier Ireland Ltd. All rights reserved. C1 NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, Bethesda, MD 20893 USA. Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY 10027 USA. Columbia Univ, Mailman Sch Publ Hlth, Div Epidemiol, New York, NY 10027 USA. New York State Psychiat Inst & Hosp, New York, NY 10032 USA. RP Grant, BE (reprint author), NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, Room 3077,MS 9304,5635 Fishers Lane, Bethesda, MD 20893 USA. EM bgrant@willco.niaaa.nih.gov FU NIAAA NIH HHS [R01AA08159, K05AA00161] NR 32 TC 50 Z9 50 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD OCT 1 PY 2005 VL 80 IS 1 BP 117 EP 123 DI 10.1016/j.drugalcdep.2005.03.010 PG 7 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 969KT UT WOS:000232233700011 PM 16157234 ER PT J AU Miksys, SL Cheung, C Gonzalez, FJ Tyndale, RF AF Miksys, SL Cheung, C Gonzalez, FJ Tyndale, RF TI Human CYP2D6 and mouse CYP2DS: Organ distribution in a humanized mouse model SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID LEWY BODY VARIANT; HUMAN BRAIN; RAT-BRAIN; AUTOIMMUNE HEPATITIS; CYTOCHROME-P450 2D6; PROTEIN EXPRESSION; ALZHEIMERS-DISEASE; DRUG-METABOLISM; MESSENGER-RNA; ENZYMES AB Polymorphic cytochrome P450 (P450) 2D6 (CYP2D6) metabolizes several classes of therapeutic drugs, endogenous neurochemicals, and toxins. A CYP2D6-humanized transgenic mouse line was previously developed to model CYP2D6-poor and - extensive metabolizer phenotypes. Human CYP2D6 was detected in the liver, kidney, and intestine of these animals. In this study, we investigated further the cellular expression and relative tissue levels of human CYP2D6 in these transgenic mice in liver, intestine, kidney, and brain. In addition, we compared this with the expression of mouse CYP2D enzymes in these organs. In humans, these organs are of interest with respect to P450-mediated drug metabolism, toxicity, and disease. The expression of human CYP2D6 and mouse CYP2D enzymes in humanized and wild-type mice was quantified by immunoblotting and detected at the cellular level by immunocytochemistry. The cell-specific expression of human CYP2D6 in liver, kidney, and intestine in humanized mice was similar to that reported in humans. The expression patterns of mouse CYP2D proteins were similar to those in humans in liver and kidney but substantially different in intestine. Human CYP2D6 was not detected in brain of transgenic mice. Mouse CYP2D proteins were detected in brain, allowing, for the first time, a direct comparison of CYP2D expression among mouse, rat, and human brain. This transgenic mouse model is useful for investigating CYP2D6-mediated metabolism in liver, kidney, and especially the intestine, where expression patterns demonstrated substantial species differences. C1 Univ Toronto, Dept Pharmacol, Toronto, ON M5S 1AB, Canada. Univ Toronto, Ctr Addict & Ment Hlth, Toronto, ON M5S 1AB, Canada. NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. RP Miksys, SL (reprint author), Univ Toronto, Dept Pharmacol, 1 Kings Coll Circle, Toronto, ON M5S 1AB, Canada. EM s.miksys@utoronto.ca RI Marion-Poll, Frederic/D-8882-2011 OI Marion-Poll, Frederic/0000-0001-6824-0180 FU Canadian Institutes of Health Research [14173] NR 39 TC 24 Z9 27 U1 0 U2 1 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 2005 VL 33 IS 10 BP 1495 EP 1502 DI 10.1124/dmd.105.005488 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 964PH UT WOS:000231892500013 PM 16033950 ER PT J AU Mathews, JM Etheridge, AS Valentine, JL Black, SR Coleman, DP Patel, P So, J Burka, LT AF Mathews, JM Etheridge, AS Valentine, JL Black, SR Coleman, DP Patel, P So, J Burka, LT TI Pharmacokinetics and disposition of the kavalactone kawain: Interaction with kava extract and kavalactones in vivo and in vitro SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID HEPATIC CYTOCHROME-P-450 ISOZYMES; METABOLISM; INHIBITION; RAT AB Reported adverse drug interactions with the popular herb kava have spurred investigation of the mechanisms by which kava could mediate these effects. In vivo and in vitro experiments were conducted to examine the effects of kava extract and individual kavalactones on cytochrome P450 ( P450) and P-glycoprotein activity. The oral pharmacokinetics of the kavalactone, kawain ( 100 mg/kg), were determined in rats with and without coadministration of kava extract ( 256 mg/kg) to study the effect of the extract on drug disposition. Kawain was well absorbed, with > 90% of the dose eliminated within 72 h, chiefly in urine. Compared with kawain alone, coadministration with kava extract caused a tripling of kawain AUC(0-8h) and a doubling of C-max. However, a 7-day pretreatment with kava extract ( 256 mg/kg/day) had no effect on the pharmacokinetics of kawain administered on day 8. The 7-day pretreatment with kava extract only modestly induced hepatic P450 activities. The human hepatic microsomal P450s most strongly inhibited by kava extract (CYP2C9, CYP2C19, CYP2D6, CYP3A4) were inhibited to the same degree by a "composite" kava formulation composed of the six major kavalactones contained in the extract. K-i values for the inhibition of CYP2C9 and CYP2C19 activities by methysticin, dihydromethysticin, and desmethoxyyangonin ranged from 5 to 10 mu M. Kava extract and kavalactones (<= 9 mu M) modestly stimulated P-glycoprotein ATPase activities. Taken together, the data indicate that kava can cause adverse drug reactions via inhibition of drug metabolism. C1 Res Triangle Inst Int, Dept Drug Metab & Pharmacokinet, Res Triangle Pk, NC 27709 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Mathews, JM (reprint author), Res Triangle Inst Int, Dept Drug Metab & Pharmacokinet, POB 12194,3040 Cornwallis Rd, Res Triangle Pk, NC 27709 USA. EM mathews@rti.org FU NIEHS NIH HHS [N01-ES-25482] NR 19 TC 51 Z9 52 U1 1 U2 5 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 2005 VL 33 IS 10 BP 1555 EP 1563 DI 10.1124/dmd.105.004317 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 964PH UT WOS:000231892500020 PM 16033948 ER PT J AU Pennington, JD Wang, TJC Nguyen, P Sun, L Bisht, K Smart, D Gius, D AF Pennington, JD Wang, TJC Nguyen, P Sun, L Bisht, K Smart, D Gius, D TI Redox-sensitive signaling factors as a novel molecular targets for cancer therapy SO DRUG RESISTANCE UPDATES LA English DT Review DE molecular targets; redox signaling; anticancer drug resistance; thioredoxin ID GLUTATHIONE-S-TRANSFERASE; TRANSCRIPTIONAL REGULATOR OXYR; THIOREDOXIN REDUCTASE SYSTEM; NF-KAPPA-B; OXIDATIVE STRESS; IONIZING-RADIATION; CELL-LINES; GENE-EXPRESSION; DNA-BINDING; HEAT-SHOCK AB Tumor cells undergoing proliferation, de-differentiation and progression depend on a complex set of respiratory pathways to generate the necessary energy. The metabolites from these pathways produce significant oxidative stress and must be buffered to prevent permanent cell damage and cell death. It is now clear that, in order to cope with and defend against the detrimental effects of oxidative stress, a series of redox-sensitive, pro-survival signaling pathways and factors regulate a complex intracellular redox buffering network. This review develops the hypothesis that tumor cells use these redox-sensitive, pro-survival signaling pathways and factors-up-regulated due to increased tumor cell respiration-to evade the damaging and cytotoxic effects of specific anticancer agents. It further suggests that redox-sensitive, signaling factors may be potential novel targets for drug discovery. C1 NCI, Mol Radiat Oncol Sect, Radiat Oncol Branch, Radiat Oncol Sci Program,Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Gius, D (reprint author), NCI, Mol Radiat Oncol Sect, Radiat Oncol Branch, Radiat Oncol Sci Program,Ctr Canc Res,NIH, Bldg 10,Room B3B69,9000 Rockville Pike, Bethesda, MD 20892 USA. EM giusd@mail.nih.gov NR 93 TC 49 Z9 50 U1 1 U2 6 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1368-7646 J9 DRUG RESIST UPDATE JI Drug Resist. Update PD OCT PY 2005 VL 8 IS 5 BP 322 EP 330 DI 10.1016/j.drup.2005.09.002 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 996ZX UT WOS:000234215900004 PM 16230045 ER PT J AU Whiteley, G Kwitkowski, V Kohn, EC AF Whiteley, G. Kwitkowski, V. Kohn, E. C. TI Ovarian cancer diagnostics: update on proteomics SO EJC SUPPLEMENTS LA English DT Meeting Abstract C1 NCI, Pathol Lab, Med Oncol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD OCT PY 2005 VL 3 IS 2 SU S BP 30 EP 30 PG 1 WC Oncology SC Oncology GA 183HV UT WOS:000247564800101 ER PT J AU Childs, RW AF Childs, R. W. TI Results in renal cell cancer: induction of graft-vs-tumor effects in renal cell carcinoma and other tumors solid tumors following allogeneic stem cell transplantation SO EJC SUPPLEMENTS LA English DT Meeting Abstract C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD OCT PY 2005 VL 3 IS 2 SU S BP 36 EP 36 PG 1 WC Oncology SC Oncology GA 183HV UT WOS:000247564800120 ER PT J AU Romond, EH Perez, EA Bryant, J Suman, V Geyer, CE Davidson, N Paik, S Martino, S Kaufman, P Wolmark, N AF Romond, E. H. Perez, E. A. Bryant, J. Suman, V. Geyer, C. E. Davidson, N. Paik, S. Martino, S. Kaufman, P. Wolmark, N. TI Doxorubicin and cyclophosphamide (AC) followed by paclitaxel (T) with or without trastuzumab (H) as adjuvant therapy for patients with HER2-positive operable breast cancer (BC): combined analysis of NSABP B-31 and NCCTG N9831 SO EJC SUPPLEMENTS LA English DT Meeting Abstract C1 Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA. US Breast Intergrp, N Cent Canc Treatment Grp, Rochester, MN USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD OCT PY 2005 VL 3 IS 2 SU S BP 73 EP 73 PG 1 WC Oncology SC Oncology GA 183HV UT WOS:000247564800243 ER PT J AU Dahut, W Posadas, E Scripture, C Gulley, J Arlen, P Wright, J Harold, N Fioravanti, S Figg, W AF Dahut, W. Posadas, E. Scripture, C. Gulley, J. Arlen, P. Wright, J. Harold, N. Fioravanti, S. Figg, W. TI A phase II study of BAY 43-9006 (sorafenib) in patients with androgen-independent prostate cancer (AlPC) SO EJC SUPPLEMENTS LA English DT Meeting Abstract C1 Natl Canc Inst, Bethesda, MD USA. Natl Canc Inst, Canc Therapy Evaluat Program, Bethesda, MD USA. RI Gulley, James/K-4139-2016; Figg Sr, William/M-2411-2016 OI Gulley, James/0000-0002-6569-2912; NR 0 TC 1 Z9 1 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD OCT PY 2005 VL 3 IS 2 SU S BP 248 EP 248 PG 1 WC Oncology SC Oncology GA 183HV UT WOS:000247564801019 ER PT J AU Oza, AM Elit, L Biagi, J Panasci, L Tonkin, K Tsao, M Dore, N Dancey, J Eisenhauer, E Seymour, L AF Oza, A. M. Elit, L. Biagi, J. Panasci, L. Tonkin, K. Tsao, M. Dore, N. Dancey, J. Eisenhauer, E. Seymour, L. TI A Phase II study of Temsirolimus (CCI-779) in patients with metastatic and/or recurrent endometrial cancer - NCICCTG IND 160 SO EJC SUPPLEMENTS LA English DT Meeting Abstract C1 Natl Canc Inst, Clin Trials Grp, Kingston, ON, Canada. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD OCT PY 2005 VL 3 IS 2 SU S BP 261 EP 261 PG 1 WC Oncology SC Oncology GA 183HV UT WOS:000247564801063 ER PT J AU Hashiguchi, Y Tsuda, H Ito, Y Ito, K Yaegashi, N Birrer, M Ohashi, Y Berkowitz, R Sako, H Mok, S AF Hashiguchi, Y. Tsuda, H. Ito, Y. Ito, K. Yaegashi, N. Birrer, M. Ohashi, Y. Berkowitz, R. Sako, H. Mok, S. TI The prediction of the response to chemotherapy and survival of patients with ovarian clear cell carcinoma by ABCF2 expression SO EJC SUPPLEMENTS LA English DT Meeting Abstract C1 Osaka City Sumiyohis Hosp, Osaka, Japan. Osaka City Gen Hosp, Osaka, Japan. Univ Tokyo, Sch Hlth Sci & Nursing, Tokyo, Japan. Tohoku Univ, Grad Sch Med, Sendai, Miyagi, Japan. Natl Canc Inst, Rockville, MD USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD OCT PY 2005 VL 3 IS 2 SU S BP 262 EP 263 PG 2 WC Oncology SC Oncology GA 183HV UT WOS:000247564801068 ER PT J AU Townsley, C Hirte, H Sharma, S Pond, G Tinker, L Afinec, A Wright, J Oza, AM AF Townsley, C. Hirte, H. Sharma, S. Pond, G. Tinker, L. Afinec, A. Wright, J. Oza, A. M. TI Phase II study of Sorafenib (BAY 43-9006) in combination with Gemcitabine in recurrent epithelial ovarian cancer - a study of the PMH phase II consortium SO EJC SUPPLEMENTS LA English DT Meeting Abstract C1 Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. NCI, CTEP, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 2 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD OCT PY 2005 VL 3 IS 2 SU S BP 272 EP 272 PG 1 WC Oncology SC Oncology GA 183HV UT WOS:000247564801099 ER PT J AU Posadas, E Kwitkowski, V Lie, M Kotz, H Minasian, L Sarosy, G Harold, N Fioravanti, S Kohn, E AF Posadas, E. Kwitkowski, V. Lie, M. Kotz, H. Minasian, L. Sarosy, G. Harold, N. Fioravanti, S. Kohn, E. TI Clinical synergism from combinatorial VEGF signal transduction inhibition in patients with advanced solid tumors - early results from a phase I study of sorafenib (BAY 43-9006) and bevacizumab SO EJC SUPPLEMENTS LA English DT Meeting Abstract C1 NCI, Med Oncol Clin Res Unit, Bethesda, MD 20892 USA. NCI, Pathol Lab, Bethesda, MD 20892 USA. NR 0 TC 4 Z9 5 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD OCT PY 2005 VL 3 IS 2 SU S BP 419 EP 420 PG 2 WC Oncology SC Oncology GA 183HV UT WOS:000247564801602 ER PT J AU Dote, H Cerna, D Burgan, W Camphausen, K Tofilon, F AF Dote, H. Cerna, D. Burgan, W. Camphausen, K. Tofilon, F. TI ErbB3 expression predicts tumor cell radiosensitization induced by Hsp90 inhibition SO EJC SUPPLEMENTS LA English DT Meeting Abstract C1 NCI, NIH, Mol Radiat Therapeut Branch, Bethesda, MD 20892 USA. NCI, NIH, Radiat Oncol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD OCT PY 2005 VL 3 IS 2 SU S BP 427 EP 427 PG 1 WC Oncology SC Oncology GA 183HV UT WOS:000247564801627 ER PT J AU Freedman, RJ Malkovska, V LeRoith, D Collins, MT AF Freedman, RJ Malkovska, V LeRoith, D Collins, MT TI Hodgkin lymphoma in temporal association with growth hormone replacement SO ENDOCRINE JOURNAL LA English DT Article DE hematology; malignancy; hormones; panhypopituitary ID CELL LYMPHOMA; FACTOR-I; LEUKEMIA; THERAPY; CANCER; ADULTS; DEFICIENCY; INSULIN; RISK; GH AB The association between growth hormone (GH) replacement and malignancy has long been debated. We report a case of Hodgkin lymphoma that developed in temporal association with the initiation of GH replacement in a 57-year-old woman with panhypopituitarism secondary to a non-secretory pituitary macroadenoma. Treatment of her pituitary tumor included transphenoidal surgery, external beam radiation, Bromocriptine and Cabergaline therapy. In addition to replacement steroid, thyroid and sex hormones, she insisted on GH replacement. Approximately, 2 years after GH initiation, the diagnosis of Hodgkin lymphoma was made. Although the exact contribution of GH to the development of Hodgkin disease in our patient is unclear and a causal effect cannot be concluded, the temporal association is suggestive, and warrants reporting as part of ongoing surveillance for potential complications of GH replacement. C1 NICHHD, Dev Endocrinol Branch, Bethesda, MD 20892 USA. Washington Hosp Ctr, Inst Canc, Washington, DC 20010 USA. NIDDK, Clin Endocrinol Branch, Bethesda, MD 20892 USA. Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Freedman, RJ (reprint author), 1500 NW 10th Ave,Suite 205, Boca Raton, FL 33484 USA. NR 25 TC 6 Z9 6 U1 0 U2 1 PU JAPAN ENDOCRINE SOCIETY PI TOKYO PA C/O DEPT VETERINARY PHYSIOL, VET MED SCI, UNIV TOKYO, 1-1-1 YAYOI, BUNKYO-KU, TOKYO, 113, JAPAN SN 0918-8959 J9 ENDOCR J JI Endocr. J. PD OCT PY 2005 VL 52 IS 5 BP 571 EP 575 DI 10.1507/endocrj.52.571 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 987NY UT WOS:000233525800011 PM 16284435 ER PT J AU Lindsay, JR Nieman, LK AF Lindsay, JR Nieman, LK TI The hypothalamic-pituitary-adrenal axis in pregnancy: Challenges in disease detection and treatment SO ENDOCRINE REVIEWS LA English DT Review ID CORTICOTROPIN-RELEASING-HORMONE; IMMUNOREACTIVE BETA-ENDORPHIN; RENIN-ANGIOTENSIN SYSTEM; AUTOIMMUNE POLYENDOCRINE SYNDROMES; CORTICOSTEROID-BINDING GLOBULIN; DEXAMETHASONE SUPPRESSION TEST; INDEPENDENT CUSHINGS-SYNDROME; TERM GLUCOCORTICOID THERAPY; RAT ANTERIOR-PITUITARY; INSULIN STRESS TESTS AB Pregnancy dramatically affects the hypothalamic-pituitary-adrenal axis leading to increased circulating cortisol and ACTH levels during gestation, reaching values in the range seen in Cushing's syndrome (CS). The cause(s) of increased ACTH may include placental synthesis and release of biologically active CRH and ACTH, pituitary desensitization to cortisol feedback, or enhanced pituitary responses to corticotropin-releasing factors. In this context, challenges in diagnosis and management of disorders of the hypothalamic-pituitary-adrenal axis in pregnancy are discussed. CS in pregnancy is uncommon and is associated with fetal morbidity and mortality. The diagnosis may be missed because of overlapping clinical and biochemical features in pregnancy. The proportion of patients with primary adrenal causes of CS is increased in pregnancy. CRH stimulation testing and inferior petrosal sinus sampling can identify patients with Cushing's disease. Surgery is a safe option for treatment in the second trimester; otherwise medical therapy may be used. Women with known adrenal insufficiency that is appropriately treated can expect to have uneventful pregnancies. Whereas a fetal/placental source of cortisol may mitigate crisis during gestation, unrecognized adrenal insufficiency may lead to maternal or fetal demise either during gestation or in the puerperium. Appropriate treatment and management of labor are reviewed. C1 NICHHD, Reprod Biol & Med Branch, NIH, Clin Res Ctr, Bethesda, MD 20892 USA. RP Nieman, LK (reprint author), NICHHD, Reprod Biol & Med Branch, NIH, Clin Res Ctr, Bldg 10,Room 1-3140,10 Ctr Dr, Bethesda, MD 20892 USA. EM niemanl@mail.nih.gov NR 321 TC 128 Z9 131 U1 1 U2 11 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0163-769X J9 ENDOCR REV JI Endocr. Rev. PD OCT PY 2005 VL 26 IS 6 BP 775 EP 799 DI 10.1210/er.2004-0025 PG 25 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 971VW UT WOS:000232414000002 PM 15827110 ER PT J AU Kim, CS Vasko, VV Kato, Y Kruhlak, M Saji, M Cheng, SY Ringel, MD AF Kim, CS Vasko, VV Kato, Y Kruhlak, M Saji, M Cheng, SY Ringel, MD TI AKT activation promotes metastasis in a mouse model of follicular thyroid carcinoma SO ENDOCRINOLOGY LA English DT Article ID PROTEIN-KINASE B; SERINE-THREONINE KINASE; PHOSPHATIDYLINOSITOL 3-KINASE; CELL-SURVIVAL; BETA-RECEPTOR; C-AKT; HORMONE; CANCER; EXPRESSION; GENE AB The phosphatidylinositol 3-kinase/AKT pathway is crucial to many cell functions, and its dysregulation in tumors is a common finding. The molecular basis of follicular thyroid cancer metastasis is not well understood but may also be influenced by AKT activation. We previously created a knockin mutant mouse that expresses a mutant thyroid hormone receptor-beta gene (TR beta PV mouse) that spontaneously develops thyroid cancer and distant metastasis similar to human follicular thyroid cancer. In this study, we investigated whether our mouse model exhibits similar AKT activation as human follicular thyroid cancer. Western blot analysis on thyroids from both wild-type and TR beta(PV/PV) mice revealed elevation of activated AKT in TR beta(PV/PV) mice. Immunohistochemistry and confocal microscopy reveal activated AKT in both the thyroid and metastatic lesions of TR beta(PV/PV) mice. Whereas all three AKT isoforms were overexpressed in primary tumors from TR beta(PV/PV) mice in the cytoplasm of thyroid cancer cells, only AKT1 was also found in the nucleus, matching the localization of activated AKT in a pattern similar to human follicular thyroid cancer. In the metastases, all AKT isoforms correlated with phosphorylated AKT nuclear localization. We created primary thyroid cell lines derived from TR beta(PV/PV) mice and found reduction of phosphorylated AKT levels or AKT downstream targets diminishes cell motility. Activated AKT is common to both human and mouse follicular thyroid cancer and is correlated with increased cell motility in vitro and metastasis in vivo. Thus, TR beta(PV/PV) mice could be used to further dissect the detailed pathways underlying the progression and metastasis of follicular thyroid carcinoma. C1 NCI, Mol Biol Lab, Bethesda, MD 20892 USA. NCI, Expt Immunol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. Ohio State Univ, Sch Med, Div Endocrinol, Columbus, OH 43210 USA. Ohio State Univ, Sch Med, Div Oncol, Columbus, OH 43210 USA. Arthur G James Canc Ctr, Columbus, OH 43210 USA. RP Cheng, SY (reprint author), NCI, Mol Biol Lab, 37 Convent Dr,Room 5128, Bethesda, MD 20892 USA. EM sycheng@helix.nih.gov FU Intramural NIH HHS NR 42 TC 67 Z9 73 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD OCT PY 2005 VL 146 IS 10 BP 4456 EP 4463 DI 10.1210/en.2005-0172 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 964QR UT WOS:000231896100038 PM 16002527 ER PT J AU Thayer, KA Melnick, R Burns, K Davis, D Huff, J AF Thayer, KA Melnick, R Burns, K Davis, D Huff, J TI Fundamental flaws of hormesis for public health decisions SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article ID FRACTIONATED-GAMMA; ATOMIC-BOMB; LONG-TERM; CADMIUM; EXPOSURE; RATS; RADIATION; CANCER; MICE; CARCINOGENESIS AB Hormesis (defined operationally as low-dose stimulation, high-dose inhibition) is often used to promote the notion that while high-level exposures to toxic chemicals could be detrimental to human health, low-level exposures would be beneficial. Some proponents claim hormesis is an adaptive, generalizable phenomenon and argue that the default assumption for risk assessments should be that toxic chemicals induce stimulatory (i.e., "beneficial") effects at low exposures. In many cases, nonmonotonic dose-response curves are called hormetic responses even in the absence of any mechanistic characterization of that response. Use of the term "hormesis," with its associated descriptors, distracts from the broader and more important questions regarding the frequency and interpretation of nonmonotonic dose responses in biological systems. A better understanding of the biological basis and consequences of nonmonotonic dose-response curves is warranted for evaluating human health risks. The assumption that hormesis is generally adaptive is an oversimplification of complex biological processes. Even if certain low-dose effects were sometimes considered beneficial, this should not influence regulatory decisions to allow increased environmental exposures to toxic and carcinogenic agents, given factors such as interindividual differences in susceptibility and multiplicity in exposures. In this commentary we evaluate the hormesis hypothesis and potential adverse consequences of incorporating low-dose beneficial effects into public health decisions. C1 NIEHS, Dept Hlth & Human Serv, NIH, Res Triangle Pk, NC 27709 USA. Sci Corps Org, Lexington, MA USA. Carnegie Mellon Univ, H John Heinz Sch Publ Policy & Management 3, Pittsburgh, PA USA. RP Thayer, KA (reprint author), NIEHS, Dept Hlth & Human Serv, NIH, MD A3-01,POB 12233, Res Triangle Pk, NC 27709 USA. EM thayer@niehs.nih.gov NR 64 TC 64 Z9 71 U1 3 U2 11 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD OCT PY 2005 VL 113 IS 10 BP 1271 EP 1276 DI 10.1289/eph.7811 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 970GF UT WOS:000232292600027 PM 16203233 ER PT J AU Kimmel, CA Collman, GW Fields, N Eskenazi, B AF Kimmel, CA Collman, GW Fields, N Eskenazi, B TI Lessons learned for the national children's study from the National Institute of Environmental Health Sciences/US Environmental Protection Agency Centers for Children's Environmental Health and Disease Prevention Research SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE asthma; autism; children; environmental health; National Children's Study; NIEHS/EPA Children's Centers; obesity; pregnancy ID PESTICIDE EXPOSURE; TOBACCO-SMOKE; POPULATION; BLOOD AB This mini-monograph was developed to highlight the experiences of the National Institute of Environmental Health Sciences (NIEHS)/U.S. Environmental Protection Agency (EPA) Centers for Children's Environmental Health and Disease Prevention Research, focusing particularly on several areas of interest for the National Children's Study. These include general methodologic issues for conducting longitudinal birth cohort studies and community-based participatory research and for measuring air pollution exposures, pesticide exposures, asthma, and neuro-behavioral toxicity. Rather than a detailed description of the studies in each of the centers, this series of articles is intended to provide information on the practicalities of conducting such intensive studies and the lessons learned. This explication of lessons learned provides an outstanding opportunity for the planners of the National Children's Study to draw on past experiences that provide information on what has and has not worked when studying diverse multiracial and multi-ethnic groups of children with unique urban and rural exposures. The Children's Centers have addressed and overcome many hurdles in their efforts to understand the link between environmental exposures and health outcomes as well as interactions between exposures and a variety of social and cultural factors. Some of the major lessons learned include the critical importance of long-term studies for assessing the full range of developmental consequences of environmental exposures, recognition of the unique challenges presented at different life stages for both outcome and exposure measurement, and the importance of ethical issues that must be dealt with in a changing medical and legal environment. It is hoped that these articles will be of value to others who are embarking on studies of children's environmental health. C1 NICHHD, Natl Childrens Study, US EPA, Bethesda, MD 20892 USA. Natl Inst Environm Hlth Sci, Div Extramural Res & Training, Dept Hlth & Human Serv, NIH, Res Triangle Pk, NC USA. US EPA, Natl Ctr Environm Res, Off Res & Dev, Washington, DC 20460 USA. Univ Calif Berkeley, Sch Publ Hlth, Ctr Childrens Environm Hlth Res, Berkeley, CA 94720 USA. RP Kimmel, CA (reprint author), NICHHD, Natl Childrens Study, US EPA, 3100 Execut Blve,Suite 5C01, Bethesda, MD 20892 USA. EM kimmelca@mail.nih.gov RI Reis, Aline/G-9573-2012 NR 25 TC 14 Z9 14 U1 1 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 2005 VL 113 IS 10 BP 1414 EP 1418 DI 10.1289/ehp.7669 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 970GF UT WOS:000232292600052 PM 16203257 ER PT J AU Galperin, MY AF Galperin, MY TI The secret of being cool SO ENVIRONMENTAL MICROBIOLOGY LA English DT Editorial Material ID COMPLETE GENOME SEQUENCE; GROUP-A STREPTOCOCCUS; TRYPANOSOMA-CRUZI; 2 STRAINS; BACTERIUM; PHOSPHODIESTERASE; TEMPERATURES; CHAPERONINS; DISEASE; GROWTH C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Galperin, MY (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM galperin@ncbi.nlm.nih.gov RI Galperin, Michael/B-5859-2013 OI Galperin, Michael/0000-0002-2265-5572 FU Intramural NIH HHS NR 28 TC 2 Z9 2 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1462-2912 J9 ENVIRON MICROBIOL JI Environ. Microbiol. PD OCT PY 2005 VL 7 IS 10 BP 1499 EP 1504 DI 10.1111/j.1462-2920.2005.00923.x PG 6 WC Microbiology SC Microbiology GA 962MO UT WOS:000231737100001 PM 16156723 ER PT J AU Nhung, BT Khan, NC Hop, LT Lien, DTK Le, DSNT Hien, VTT Kunii, D Sakai, T Nakamori, M Yamamoto, S AF Nhung, BT Khan, NC Hop, LT Lien, DTK Le, DSNT Hien, VTT Kunii, D Sakai, T Nakamori, M Yamamoto, S TI FAO/WHO/UNU equations overestimate resting metabolic rate in Vietnamese adults SO EUROPEAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE resting metabolic rate; Vietnamese; equation ID PREDICTIVE EQUATIONS; WOMEN; MEN AB Objective: To evaluate the FAO/WHO/UNU equations for predicting resting metabolic rate (RMR) in Vietnamese adults. Design: A cross-sectional study with healthy subjects was carried out at the Basic Nutrition Department, National Institute of Nutrition, Vietnam. RMR was measured by indirect calorimetry, and anthropometric indices were recorded. Equations derived by linear regression of RMR vs body weight were compared to the FAO/WHO/UNU 1985 predictive equations. Subjects: A total of 188 subjects ( 98 males and 90 females) had a normal body mass index (BMI) and were divided into four groups by sex and age ( male and female subjects 18 - 29 and 30 - 60 y old). Results: Mean RMR (MJ/kg/day) in males was lightly significant by higher than that in female subjects in the 18 - 29 y old age group ( 0.1074 +/- 0.0100 vs 0.0965 +/- 0.0123) and the same result was seen in the 30 - 60 y old group (0.1018 +/- 0.0114 vs 0.0922 +/- 0.0129). However, differences were not statistically significant in the two age groups. Compared to the FAO/WHO/ UNU equation, our findings were 7.4, 9.0, 11.7, and 13.5% lower in the four groups, respectively (P<0.001). Conclusion: Our findings suggest that the FAO/WHO/ UNU equations may overestimate RMR in Vietnamese adults. Further studies examining the relationship between body weight and RMR are needed, and establishing new predictive equations for RMR in Vietnamese should be a priority. C1 Univ Tokushima, Sch Med, Dept Nutr, Tokushima 770, Japan. Natl Inst Nutr, Hanoi, Vietnam. Natl Inst Hlth, Phoenix, AZ USA. RP Yamamoto, S (reprint author), Univ Tokushima, Grad Sch Hlth Biosci, 3 Kuramoto, Tokushima 7708503, Japan. EM syamamoto@nutr.med.tokushima-u.ac.jp NR 24 TC 14 Z9 15 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0954-3007 J9 EUR J CLIN NUTR JI Eur. J. Clin. Nutr. PD OCT PY 2005 VL 59 IS 10 BP 1099 EP 1104 DI 10.1038/sj.ejcn.1602199 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 970NZ UT WOS:000232318200001 PM 16015275 ER PT J AU Huynh, TT Pacak, K Brouwers, FM Abu-Asab, MS Worrell, RA Walther, MC Elkahloun, AG Goldstein, DS Cleary, S Eisenhofer, G AF Huynh, TT Pacak, K Brouwers, FM Abu-Asab, MS Worrell, RA Walther, MC Elkahloun, AG Goldstein, DS Cleary, S Eisenhofer, G TI Different expression of catecholamine transporters in phaeochromocytomas from patients with von Hippel-Lindau syndrome and multiple endocrine neoplasia type 2 SO EUROPEAN JOURNAL OF ENDOCRINOLOGY LA English DT Article ID RAT ADRENAL-MEDULLA; NORADRENALINE TRANSPORTER; CHROMAFFIN CELLS; PLASMA; METAIODOBENZYLGUANIDINE; NOREPINEPHRINE; METANEPHRINES; PHENOTYPES; DIAGNOSIS; GRANULES AB Objective: Phaeochromocytomas in patients with multiple endocrine neoplasia type 2 (MEN 2) produce adrenaline, whereas those with von Hippel-Lindau (VHL) syndrome do not. This study assessed whether these distinctions relate to differences in expression of the transporters responsible for uptake and storage of catecholamines - the noradrenaline transporter and the vesicular monoamine transporters (VMAT 1 and VMAT 2). Methods: Tumour tissue and plasma samples were obtained from 31 patients with hereditary phaeochromocytoma - 18 with VHL syndrome and 13 with MEN 2. We used quantitative PCR, Western blotting, electron microscopy, immunohistochemistry and measurements of plasma and tumour catecholamines to assess differences in expression of the transporters in noradrenaline-producing vs adrenaline-producing hereditary tumours. These differences were compared with those in a further group of 26 patients with non-syndromic phaeochromocytoma. Results: Adrenaline-producing phaeochromocytomas in MEN 2 patients expressed more noradrenaline transporter mRNA and protein than noradrenaline-producing tumours in VHL patients. In contrast. there was greater expression of VMAT 1 in VHL than MEN 2 tumours, while expression of VMAT 2 did not differ significantly. These differences were associated with larger numbers of storage vesicles and higher tissue contents of catecholamines in MEN 2 than in VHL tumours. Differences in expression of the noradrenaline transporter were weaker, and those of VMAT 1 and VMAT 2 stronger, in noradrenaline and adrenaline-producing non-syndromic than in hereditary tumours. Conclusions: The findings show that, in addition to differences in catecholamine biosynthesis, phaeochromocytomas in MEN 2 and VHL syndrome also differ in expression of the transporters responsible for uptake and vesicular storage of catecholamines. C1 NCI, Clin Neurocardiol Sect, NINDS, NIH, Bethesda, MD 20892 USA. NCI, Reprod Biol & Med Branch, NICHHD, Bethesda, MD USA. NCI, Pathol Lab, Bethesda, MD USA. NCI, Urol Oncol Branch, Bethesda, MD USA. NHGRI, Genome Technol Branch, NIH, Bethesda, MD USA. RP Eisenhofer, G (reprint author), NCI, Clin Neurocardiol Sect, NINDS, NIH, Bldg 10,Room 6N252,10 Ctr Dr,MSC-1620, Bethesda, MD 20892 USA. EM ge@box-g.nih.gov OI Abu-Asab, Mones/0000-0002-4047-1232 FU Intramural NIH HHS [Z99 CA999999] NR 27 TC 31 Z9 33 U1 0 U2 0 PU BIO SCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0804-4643 J9 EUR J ENDOCRINOL JI Eur. J. Endocrinol. PD OCT PY 2005 VL 153 IS 4 BP 551 EP 563 DI 10.1530/eje.1.01987 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 976FL UT WOS:000232718200012 PM 16189177 ER PT J AU Kullberg, MC Hay, V Cheever, AW Mamura, M Sher, A Letterio, JJ Shevach, EM Piccirillo, CA AF Kullberg, MC Hay, V Cheever, AW Mamura, M Sher, A Letterio, JJ Shevach, EM Piccirillo, CA TI TGF-beta 1 production by CD4(+)CD25(+) regulatory T cells is not essential for suppression of intestinal inflammation SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE CD4(+) regulatory T cells; TGF-beta; autoimmunity; suppression ID GROWTH-FACTOR-BETA; TGF-BETA; CUTTING EDGE; PERIPHERAL TOLERANCE; TARGETED DISRUPTION; IMMUNE-RESPONSES; IN-VITRO; MICE; COLITIS; ACTIVATION AB Naturally occurring CD4(+)CD25(+) regulatory T cells (Treg) are potent suppressors of CD4(+) and CD8(+) T cell responses in vitro and inhibit several organ-specific autoimmune diseases. While most in vitro studies suggest that CD4+CD25+ Treg cells adopt a cytokine-independent but cell contact-dependent mode of T cell regulation, their precise mechanism of suppression in vivo remains largely unknown. Here we examine the functional contribution of Treg cell-derived TGF-beta 1 and effector T cell responsiveness to TGF-beta in CD4(+)CD25(+) T cell-mediated suppression of inflammatory bowel disease (IBD). We show that CD4(+)CD25(+) Treg cells from either TGF-beta 1(+/+) or neonatal TGF-beta 1(-/-) mice can suppress the incidence and severity of IBD as well as colonic IFN-gamma mRNA expression induced by WT CD4(+)CD25(-) effector T cells. Furthermore, TGF-beta-resistant Smad3(-/-) CD4(+)CD25(+) Treg cells are equivalent to WT Treg cells in their capacity to suppress disease induced by either WT or Smad3(-/-) CD4(+)CD25(-) effector T cells. Finally, anti-TGF-beta treatment exacerbates the colitogenic potential of CD4(+)CD25(-) effector T cells in the absence of CD4(+)CD25(+) Treg cells. Together, these data demonstrate that in certain situations CD4(+)CD25(+) T cells are able to suppress intestinal inflammation by a mechanism not requiring Treg cell-derived TGF-beta 1 or effector T cell/Treg cell responsiveness to TGF-beta via Smad3. C1 McGill Univ, Dept Microbiol & Immunol, Montreal, PQ H3A 2B4, Canada. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Biomed Res Inst, Rockville, MD 20852 USA. NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bethesda, MD 20892 USA. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Piccirillo, CA (reprint author), McGill Univ, Dept Microbiol & Immunol, 3775 Univ St, Montreal, PQ H3A 2B4, Canada. EM ciro.piccirillo@mcgill.ca OI Mamura, Mizuko/0000-0003-4531-0144 NR 42 TC 85 Z9 91 U1 0 U2 0 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD OCT PY 2005 VL 35 IS 10 BP 2886 EP 2895 DI 10.1002/eji.200526106 PG 10 WC Immunology SC Immunology GA 976SE UT WOS:000232752800011 PM 16180248 ER PT J AU Dar, DE Thiruvazhi, M Abraham, P Kitayama, S Kopajtic, TA Gamliel, A Slusher, BS Carroll, FI Uhl, GR AF Dar, DE Thiruvazhi, M Abraham, P Kitayama, S Kopajtic, TA Gamliel, A Slusher, BS Carroll, FI Uhl, GR TI Structure-activity relationship of trihexyphenidyl analogs with respect to the dopamine transporter in the on going search for a cocaine inhibitor SO EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article DE trihexyphenidyl; dopamine; cocaine; n-methylscopolamine; transporter; uptake; binding ID ACID METHYL-ESTERS; LOCOMOTOR STIMULANT; SELECTIVE COMPOUNDS; BINDING-PROPERTIES; RECOGNITION SITES; RELEASE INHIBITOR; LIGAND-BINDING; HIGH-AFFINITY; CGS 10746B; RAT AB A series of trihexyphenidyl (THP) analogs were used to search for a derivative that could serve as a cocaine inhibitor. A compound that blocks binding of the cocaine analog carboxyfluorotropane (CFT), allows dopamine uptake and exhibits low side effects could serve as a good candidate for that purpose. All analogs were tested for the extent to which they inhibit CFT binding, dopamine uptake and n-methyl scopolamine (NMS) binding. Several structure-function relationships emerged. Methylation/halogenation of THP's benzene ring enhanced the compound's ability to block CFT binding in comparison to its ability to block dopamine uptake (5a-e). Replacement of the cyclohexyl ring with a benzene ring tended to create compounds that had lower affinities to the dopamine transporter (7b compared to THP, 7d compared to 5h, 7c compared to 8c) and modification of THP's piperidine ring tended to enhance affinity to the dopamine transporter (5f-h, 8a, 8c). One analog (5f) that showed little muscarinic activity indicating that it would probably have few side effects was investigated for its effects as an in vivo cocaine inhibitor. However, it showed few antagonistic effects in vivo. Nevertheless, this work greatly elucidates the structure-function relationships required for potential cocaine inhibitors and so lays out promising directions for future research. (c) 2005 Elsevier SAS. All rights reserved. C1 Natl Inst Drug Abuse, Intramural Res Program, Mol Neurobiol Branch, NIH, Baltimore, MD 21224 USA. Res Triangle Inst, Res Triangle Pk, NC 27709 USA. Quark Biotech Inc, IL-70400 Ness Ziona, Israel. Guilford Pharmaceut, Dept Res, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD 21205 USA. RP Dar, DE (reprint author), Weizmann Inst Sci, IL-76100 Rehovot, Israel. EM dalit.dar@weizmann.ac.il NR 44 TC 7 Z9 8 U1 1 U2 1 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0223-5234 J9 EUR J MED CHEM JI Eur. J. Med. Chem. PD OCT PY 2005 VL 40 IS 10 BP 1013 EP 1021 DI 10.1016/j.ejmech.2005.04.016 PG 9 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 976SC UT WOS:000232752500006 PM 16009468 ER PT J AU Schou, M Halldin, C Pike, VW Mozley, PD Dobson, D Innis, RB Farde, L Hall, H AF Schou, M Halldin, C Pike, VW Mozley, PD Dobson, D Innis, RB Farde, L Hall, H TI Post-mortem human brain autoradiography of the norepinephrine transporter using (S,S)-[F-18]FMeNER-D-2 SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Article DE norepinephrine transporter; autoradiography; (S,S)-[F-18]FMeNER-D-2; human brain ID H-3 NISOXETINE; UPTAKE INHIBITOR; LOCUS-COERULEUS; BINDING-SITES; RADIOLIGAND; SEROTONIN AB The binding of the norepinephrine transporter radioligand, (S,S)-[F-18]FMeNER-D-2, to human brain post-mortem was examined in vitro by whole hemisphere autoradiography. The rank order for the density of labelling was: locus coeruleus >> cortex approximate to cerebellum approximate to thalamus > caudate approximate to putamen. The NET-selectivity of binding was confirmed by co-incubation with desipramine. The dual NET/SERT inhibitor duloxetine also inhibited specific binding, whereas PE2I or citalopram had no evident effect. (c) 2005 Elsevier B.V. and ECNP. All rights reserved. C1 Karolinska Hosp, Psychiat Sect, Dept Clin Neurosci, Karolinska Inst, S-17176 Stockholm, Sweden. NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. Eli Lilly Co, Indianapolis, IN 46285 USA. RP Schou, M (reprint author), Karolinska Hosp, Psychiat Sect, Dept Clin Neurosci, Karolinska Inst, S-17176 Stockholm, Sweden. EM magnus.schou@cns.ki.se NR 21 TC 47 Z9 47 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD OCT PY 2005 VL 15 IS 5 BP 517 EP 520 DI 10.1016/j.euroneuro.2005.01.007 PG 4 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 969VQ UT WOS:000232263900005 PM 16139169 ER PT J AU Baas, JM Lissek, S Pine, DS Levine, J Lawley, M Ellis, V Grillon, C AF Baas, JM Lissek, S Pine, DS Levine, J Lawley, M Ellis, V Grillon, C TI The benzodiazepine alprazolam reduces contextual fear but not cued fear-potentiated startle in humans SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 18th ECNP Congress 2005 CY OCT 22-26, 2005 CL Amsterdam, NETHERLANDS SP ECNP C1 Univ Utrecht, Utrecht, Netherlands. NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. RI Lissek, Shmuel/B-6577-2008 NR 2 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD OCT PY 2005 VL 15 SU 3 BP S552 EP S552 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 992CA UT WOS:000233860601140 ER PT J AU Colantuoni, C Weinberger, DR Kleinman, J Hyde, T Aguirre, C Creswell, J Chen, J Melhem, S Kolachana, B Straub, R Freed, W Lehrmann, E Becker, K Wood, W AF Colantuoni, C Weinberger, DR Kleinman, J Hyde, T Aguirre, C Creswell, J Chen, J Melhem, S Kolachana, B Straub, R Freed, W Lehrmann, E Becker, K Wood, W TI The cortical gene expression profile as a phenotype in genetic association SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 18th ECNP Congress 2005 CY OCT 22-26, 2005 CL Amsterdam, NETHERLANDS SP ECNP C1 NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. NIDA, NIH, Bethesda, MD 20892 USA. NIA, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD OCT PY 2005 VL 15 SU 3 BP S342 EP S343 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 992CA UT WOS:000233860600091 ER PT J AU Drevets, WC AF Drevets, WC TI Functional genetic polymorphisms and emotion processing SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 18th ECNP Congress 2005 CY OCT 22-26, 2005 CL Amsterdam, NETHERLANDS SP ECNP C1 NIMH, Sect Neuroimaging Mood & Anxiety, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD OCT PY 2005 VL 15 SU 3 BP S354 EP S355 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 992CA UT WOS:000233860600128 ER PT J AU Giedd, JN AF Giedd, JN TI ADHD: new views from brain imaging SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 18th ECNP Congress 2005 CY OCT 22-26, 2005 CL Amsterdam, NETHERLANDS SP ECNP C1 NIMH, Brain Imaging Unit, Child Psychiat Branch, Bethesda, MD 20892 USA. RI Giedd, Jay/A-3080-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD OCT PY 2005 VL 15 SU 3 BP S351 EP S352 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 992CA UT WOS:000233860600119 ER PT J AU Hommer, DW Bjork, JM Momenan, R Schottenbauer, M AF Hommer, DW Bjork, JM Momenan, R Schottenbauer, M TI Brain structural collaterals of alcoholism SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 18th ECNP Congress 2005 CY OCT 22-26, 2005 CL Amsterdam, NETHERLANDS SP ECNP C1 NIAAA, NIH, Bethesda, MD USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD OCT PY 2005 VL 15 SU 3 BP S340 EP S340 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 992CA UT WOS:000233860600084 ER PT J AU McClure, EI Monk, CS Nelson, EE Schweder, AE Roberson-Nay, R Parrish, J Adler, A Leibenluft, E Charney, DS Ernst, M Pine, DS AF McClure, EI Monk, CS Nelson, EE Schweder, AE Roberson-Nay, R Parrish, J Adler, A Leibenluft, E Charney, DS Ernst, M Pine, DS TI Attention modulates neural activation to emotional facial expressions in adolescents with anxiety disorders SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 18th ECNP Congress 2005 CY OCT 22-26, 2005 CL Amsterdam, NETHERLANDS SP ECNP C1 NIMH, Sect Dev & Affect Neurosci, Bethesda, MD 20892 USA. NIMH, Unit Affect Disorders, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD OCT PY 2005 VL 15 SU 3 BP S526 EP S526 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 992CA UT WOS:000233860601086 ER PT J AU Merikangas, KR Grillon, C Kessler, R Low, N AF Merikangas, KR Grillon, C Kessler, R Low, N TI Specificity of individual and familial patterns of anxiety disorders SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 18th ECNP Congress 2005 CY OCT 22-26, 2005 CL Amsterdam, NETHERLANDS SP ECNP C1 NIMH, Sect Dev Genet Epidemiol, Bethesda, MD 20892 USA. NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD OCT PY 2005 VL 15 SU 3 BP S347 EP S347 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 992CA UT WOS:000233860600105 ER PT J AU Mol, N Baas, JMP Grillon, C Kenemans, JL AF Mol, N Baas, JMP Grillon, C Kenemans, JL TI A model for dissociating fear and anxiety in event-related designs SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 18th ECNP Congress 2005 CY OCT 22-26, 2005 CL Amsterdam, NETHERLANDS SP ECNP C1 Univ Utrecht, Utrecht, Netherlands. NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD OCT PY 2005 VL 15 SU 3 BP S552 EP S553 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 992CA UT WOS:000233860601141 ER PT J AU Nadri, C Lipska, BK Agam, G Belmaker, RH AF Nadri, C Lipska, BK Agam, G Belmaker, RH TI Are protein alterations in schizophrenia due to early environmental insult? SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 18th ECNP Congress 2005 CY OCT 22-26, 2005 CL Amsterdam, NETHERLANDS SP ECNP C1 Ben Gurion Univ Negev, IL-84105 Beer Sheva, Israel. Stanley Res Ctr, Fac Hlth Sci, Mental Hlth Ctr, Beer Sheva, Israel. NIMH, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD OCT PY 2005 VL 15 SU 3 BP S317 EP S318 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 992CA UT WOS:000233860600014 ER PT J AU Pezawas, L Kasper, S Wittchen, HU AF Pezawas, L Kasper, S Wittchen, HU TI The bipolar epidemic. Fact or artefact SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 18th ECNP Congress 2005 CY OCT 22-26, 2005 CL Amsterdam, NETHERLANDS SP ECNP C1 NIMH, Cognit & Psychosis Program, Bethesda, MD USA. Med Univ Vienna, Vienna, Austria. Tech Univ Dresden, Inst Clin Psychol & Psychotherapy, Dresden, Germany. RI Wittchen, Hans-Ulrich/A-8507-2014 NR 3 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD OCT PY 2005 VL 15 SU 3 BP S317 EP S317 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 992CA UT WOS:000233860600012 ER PT J AU Szabo, ST Einat, H Chen, W Falke, C Du, J Manji, HK AF Szabo, ST Einat, H Chen, W Falke, C Du, J Manji, HK TI Neurogranin: a critical molecule at the nexus of 3 major signaling pathways and mood modulation SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 18th ECNP Congress 2005 CY OCT 22-26, 2005 CL Amsterdam, NETHERLANDS SP ECNP C1 NIMH, Mol Pathophysiol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD OCT PY 2005 VL 15 SU 3 BP S363 EP S363 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 992CA UT WOS:000233860600147 ER PT J AU Weinberger, DR AF Weinberger, DR TI Psychiatric genes and gene expression in psychiatry SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 18th ECNP Congress 2005 CY OCT 22-26, 2005 CL Amsterdam, NETHERLANDS SP ECNP C1 NIMH, Cognit & Psychosis Program, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD OCT PY 2005 VL 15 SU 3 BP S343 EP S343 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 992CA UT WOS:000233860600093 ER PT J AU Winkler, D Pjrek, EP Konstantinidis, A Stastny, J Praschak-Rieder, N Willeit, M Pezawas, L Kasper, S AF Winkler, D Pjrek, EP Konstantinidis, A Stastny, J Praschak-Rieder, N Willeit, M Pezawas, L Kasper, S TI Chronobiological abnormalities in seasonal affective disorder measured with actigraphy SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 18th ECNP Congress 2005 CY OCT 22-26, 2005 CL Amsterdam, NETHERLANDS SP ECNP C1 Med Univ Vienna, Dept Gen Psychiat, Vienna, Austria. Ctr Addict & Mental Hlth, Toronto, ON, Canada. NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-977X J9 EUR NEUROPSYCHOPHARM JI Eur. Neuropsychopharmacol. PD OCT PY 2005 VL 15 SU 3 BP S391 EP S392 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 992CA UT WOS:000233860600214 ER PT J AU Xiao, XD Sidorov, IA Gee, J Lempicki, RA Dimitrov, DS AF Xiao, XD Sidorov, IA Gee, J Lempicki, RA Dimitrov, DS TI Retinoic acid-induced downmodulation of telomerase activity in human cancer cells SO EXPERIMENTAL AND MOLECULAR PATHOLOGY LA English DT Article DE telomerase regulation; retinoic acid; c-Myc ID REVERSE-TRANSCRIPTASE GENE; CATALYTIC SUBUNIT HTERT; C-MYC; PROMOTER; IDENTIFICATION; ACTIVATION; EXPRESSION; CLONING AB Most human cancers express telomerase but its activity is highly variable and regulated by complex mechanisms. Recently, several studies have suggested that retinoic acid (RA) downregulates telomerase activity and that this effect could be a major determinant of its therapeutic activity. To elucidate possible mechanisms of RA-mediated downinodulation of teloinerase activity, we measured the kinetics of concentration changes of several transcription regulators by using standard biochemical techniques at low (10 mu M) and high (100 mu M) RA concentrations. We further evaluated the global impact of the RA treatment on gene expression profiles using microarray. It was found that the kinetics of c-Myc correlates most closely with the telomerase activity suggesting in agreement with previous studies that this protein is a major intermediate of the RA-induced downregulation of telomerase activity. Other telomerase regulators as Spl and Madl did not exhibit significant correlation. The dominant role of c-Myc in RA-induced telomerase dowrimodulation is confirmed by microarray data. Additionally, a number of proteins were found as possible correlates of telomerase activity by microarray analysis. These data suggest a complex interplay between c-Myc and other proteins that may be important determinants of the RA effects on telomerase activity in human cancer cells. The complex mechanism through which telomerase activity is controlled during differentiation and cancer transformation is also reflected. Published by Elsevier Inc. C1 NCI, Prot Interact Grp, Lab Expt & Computat Biol, NIH, Frederick, MD 21702 USA. SAIC, Frederick, MD 21702 USA. RP Xiao, XD (reprint author), NCI, Prot Interact Grp, Lab Expt & Computat Biol, NIH, Bldg 469,Rm 139,POB B,Miller Dr, Frederick, MD 21702 USA. EM xiaox@ncifcrf.gov RI Lempicki, Richard/E-1844-2012 OI Lempicki, Richard/0000-0002-7059-409X NR 19 TC 9 Z9 9 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4800 J9 EXP MOL PATHOL JI Exp. Mol. Pathol. PD OCT PY 2005 VL 79 IS 2 BP 108 EP 117 DI 10.1016/j.jexmp.2005.06.001 PG 10 WC Pathology SC Pathology GA 968VF UT WOS:000232190300004 PM 16054129 ER PT J AU Amedi, A von Kriegstein, K van Atteveldt, NM Beauchamp, MS Naumer, MJ AF Amedi, A von Kriegstein, K van Atteveldt, NM Beauchamp, MS Naumer, MJ TI Functional imaging of human crossmodal identification and object recognition SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article; Proceedings Paper CT 5th International Multisensory Research Forum CY JUN 02-05, 2004 CL Barcelona, SPAIN DE object recognition; crossmodal; audio-visual; visuo-tactile; multisensory; functional magnetic resonance imaging (fMRI) ID VISUAL SPEECH-PERCEPTION; FUSIFORM FACE AREA; HUMAN BRAIN; AUDITORY-CORTEX; MULTISENSORY CONVERGENCE; AUDIOVISUAL SPEECH; MULTIMODAL AGNOSIA; EXPLICIT MEMORY; NEURAL PATHWAYS; PARIETAL CORTEX AB The perception of objects is a cognitive function of prime importance. In everyday life, object perception benefits from the coordinated interplay of vision, audition, and touch. The different sensory modalities provide both complementary and redundant information about objects, which may improve recognition speed and accuracy in many circumstances. We review crossmodal studies of object recognition in humans that mainly employed functional magnetic resonance imaging (fMRI). These studies show that visual, tactile, and auditory information about objects can activate cortical association areas that were once believed to be modality-specific. Processing converges either in multisensory zones or via direct crossmodal interaction of modality-specific cortices without relay through multisensory regions. We integrate these findings with existing theories about semantic processing and propose a general mechanism for crossmodal object recognition: The recruitment and location of multisensory convergence zones varies depending on the information content and the dominant modality. C1 Frankfurt Med Sch, Inst Med Psychol, D-60528 Frankfurt, Germany. Boston Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Neurol,Lab Magnet Brain Stimulat, Boston, MA 02118 USA. Goethe Univ Frankfurt, Cognit Neurol Unit, D-6000 Frankfurt, Germany. Brain Imaging Ctr, Frankfurt, Germany. Univ Maastricht, Fac Psychol, Dept Cognit Neurosci, Maastricht, Netherlands. NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. Max Planck Inst Brain Res, Dept Neurophysiol, D-60496 Frankfurt, Germany. RP Naumer, MJ (reprint author), Frankfurt Med Sch, Inst Med Psychol, Heinrich Hoffmann Str 10, D-60528 Frankfurt, Germany. EM m.j.naumer@med.uni-frankfurt.de RI von Kriegstein, Katharina/C-3135-2008; OI von Kriegstein, Katharina/0000-0001-7989-5860; Beauchamp, Michael/0000-0002-7599-9934 NR 131 TC 208 Z9 210 U1 6 U2 34 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD OCT PY 2005 VL 166 IS 3-4 BP 559 EP 571 DI 10.1007/s00221-005-2396-5 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 976GQ UT WOS:000232721400028 PM 16028028 ER PT J AU Cremazy, FGE Manders, EMM Bastiaens, PIH Kramer, G Hager, GL van Munster, EB Verschure, PJ Gadella, TWJ van Driel, R AF Cremazy, FGE Manders, EMM Bastiaens, PIH Kramer, G Hager, GL van Munster, EB Verschure, PJ Gadella, TWJ van Driel, R TI Imaging in situ protein-DNA interactions in the cell nucleus using FRET-FLIM SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE FRET; FLIM; DNA; chromatin; histone H2B; glucocorticoid receptor; HP1; GFP; DNA-binding protein; transcription factor ID GLUCOCORTICOID-RECEPTOR; LIVING CELLS; RAPID EXCHANGE; MICROSCOPY; DOMAINS; VIVO; HP1; MAINTENANCE; VARIANTS; DYNAMICS AB Although the distribution of DNA-binding proteins inside the cell nucleus can be analyzed by immunolabeling or by tagging proteins with GFP, we cannot establish whether the protein is bound to DNA or not. Here, we describe a novel approach that allows imaging of the in situ interaction between a GFP-fusion protein and DNA in the cell nucleus, using fluorescence resonance energy transfer (FRET). We used fluorescence lifetime imaging microscopy (FLIM) as a reliable tool to detect protein in contact with DNA. The method was successfully applied to the DNA-binding proteins histone H2B and the glucocorticoid receptor and to the heterochromatin-associated proteins HB1 alpha and HP1 beta. (c) 2005 Elsevier Inc. All rights reserved. C1 Univ Amsterdam, BioCentrum Amsterdam, Swammerdar Inst Life Sci, NL-1098 SM Amsterdam, Netherlands. European Mol Biol Lab, Cell Biol & Celll Biophys, D-69117 Heidelberg, Germany. NCI, Lab Receptor Biol & Gene Express, Bethesda, MD 20892 USA. RP van Driel, R (reprint author), Univ Amsterdam, BioCentrum Amsterdam, Swammerdar Inst Life Sci, Kruislaan 318, NL-1098 SM Amsterdam, Netherlands. EM van.driel@science.uva.nl RI Manders, Erik/D-1983-2009; OI Kramer, Gertjan/0000-0002-8541-0337 NR 31 TC 38 Z9 41 U1 1 U2 14 PU ELSEVIER INC PI SAN DIEGO PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495, UNITED STATES SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD OCT 1 PY 2005 VL 309 IS 2 BP 390 EP 396 DI 10.1016/j.yexcr.2005.06.007 PG 7 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 969TT UT WOS:000232258400015 PM 16040027 ER PT J AU Qtaishat, NM Wiggert, B Pepperberg, DR AF Qtaishat, NM Wiggert, B Pepperberg, DR TI Interphotoreceptor retinoid-binding protein (IRBP) promotes the release of all-trans retinol from the isolated retina following rhodopsin bleaching illumination SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE interphotoreceptor retinoid-binding protein; IRBP; visual cycle; rod photoreceptor; retinol; rhodopsin ID VISUAL PIGMENT REGENERATION; BOVINE RETINA; EYE TISSUES; EPITHELIUM; MICE; PHOTORECEPTORS; KINETICS; CYCLE; PHOSPHORYLATION; BIOCHEMISTRY AB All-trans retinol generated in rod photoreceptors upon the bleaching of rhodopsin is known to move from the rods to the retinal pigment epithelium (RPE), where it is enzymatically converted to 11-cis retinal in the retinoid visual cycle. Interphotoreceptor retinoid-binding protein (IRBP) contained in the extracellular compartment (interphotoreceptor matrix) that separates the retina and RPE has been hypothesized to facilitate this movement of all-trans retinol, but the precise role of IRBP in this process remains unclear. To examine the activity of IRBP in the release of all-trans retinol from the rods, initially dark-adapted isolated retinas obtained from toad (Bufo marinas) eyes were bleached and then incubated in darkness for defined periods (5-180 min) in physiological saline (Ringer solution) supplemented with IRBP (here termed 'IRBP I') at defined concentrations (2-90 mu M). Retinoids present in the retina and extracellular medium were then determined by extraction and HPLC analysis. Preparations incubated with >= 10 mu M IRBP I showed a pronounced release of all-trans retinol with increasing period of incubation. As determined with 25 pm IRBP 1, the increase of all-trans retinol in the extracellular medium was accompanied by a significant decrease in the combined amount of all-trans retinal and all-trans retinol contained in the retina. This effect was not mimicked by unsupplemented Ringer solution or by Ringer solution containing 25 or 90 pm bovine serum albumin. However, incubation with IRBP II', a previously described variant of IRBP with altered lectin-binding properties, led to the appearance of substantial all-trans retinol in the extracellular medium. The results suggest that in vivo, IRBP plays a direct role in the release of all-trans retinol from the rods during operation of the visual cycle. (c) 2005 Elsevier Ltd. All rights reserved. C1 Univ Illinois, Coll Med, Lions Illinois Eye Res Inst, Dept Ophthalmol & Visual Sci, Chicago, IL 60612 USA. NEI, Bethesda, MD 20892 USA. RP Pepperberg, DR (reprint author), Univ Illinois, Coll Med, Lions Illinois Eye Res Inst, Dept Ophthalmol & Visual Sci, 1855 W Taylor St, Chicago, IL 60612 USA. EM davipepp@uic.edu FU NEI NIH HHS [EY01792, EY05494] NR 47 TC 25 Z9 25 U1 0 U2 0 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD OCT PY 2005 VL 81 IS 4 BP 455 EP 463 DI 10.1016/j.exer.2005.03.005 PG 9 WC Ophthalmology SC Ophthalmology GA 975HA UT WOS:000232650400015 PM 15935345 ER PT J AU Stroncek, D Slezak, S Khuu, H Basil, C Tisdale, J Leitman, SF Marincola, FM Panelli, MC AF Stroncek, D Slezak, S Khuu, H Basil, C Tisdale, J Leitman, SF Marincola, FM Panelli, MC TI Proteomic signature of myeloproliferation and neutrophilia: analysis of serum and plasma from healthy subjects given granulocyte colony-stimulating factor SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID BLOOD STEM-CELLS; BONE-MARROW-TRANSPLANTATION; CHRONIC NEUTROPENIA; PROGENITOR CELLS; LEUKEMIA; MOBILIZATION; LACTOFERRIN; RECEPTOR; MYELOPEROXIDASE; REGENERATION AB Objective. Proteomic analysis could improve our understanding of the mechanisms and consequences of myeloproliferation. Healthy subjects treated with granulocyte colony-stimulating factor (G-CSF) were used as a model of myeloproliferation. Methods. Levels of 80 soluble factors were measured by enzyme-linked immunosorbent assay before and after 5 days of G-CSF. Both serum and plasma levels were measured to generate a comprehensive profile and determine whether serum or plasma best portrays biological and physiological changes. Results. Comparison of samples collected prior to G-CSF demonstrated that 44 factors differed between serum and plasma. Concentrations of several growth factors and chemokines were greater in serum than in plasma, while the opposite was true for several interleukins. Following G-CSF serum levels of 14 factors and plasma levels of 15 factors changed. Eleven increased in both serum and plasma, including cell adhesion molecules (vascular cell adhesion molecule-1, E-selectin, and L-selectin), matrix metalloproteases (MMP-1, -8, and -13), cytokine receptors (tumor necrosis factor receptor 1 and 2, and interleukin-2 receptor), the acute phase reactant, serum amyloid A, and a growth factor, hepatocyte growth factor. Conclusion. Some protein levels differ markedly in serum and plasma. Myeloproliferation is associated with changes in the levels of several proteases, adhesion molecules, and cytokines. (c) 2005 International Society for Experimental Hematology. C1 NIH, Dept Transfus Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. NIDDKD, Mol & Clin Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Stroncek, D (reprint author), NIH, Dept Transfus Med, Warren G Magnuson Clin Ctr, Bldg 10,Rm 1C711 10 Ctr Dr,MSC-1184, Bethesda, MD 20892 USA. EM dstroncek@cc.nih.gov NR 35 TC 9 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD OCT PY 2005 VL 33 IS 10 BP 1109 EP 1117 DI 10.1016/j.exphem.2005.06.029 PG 9 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 981GM UT WOS:000233075600006 PM 16219533 ER PT J AU Conrads, TP Hood, BL Petricoin, EF Liotto, LA Veenstra, TD AF Conrads, Thomas P. Hood, Brian L. Petricoin, Emmanuel F., III Liotto, Lance A. Veenstra, Timothy D. TI Cancer proteomics: many technologies, one goal SO EXPERT REVIEW OF PROTEOMICS LA English DT Review DE biomarkers; multidimensional separations; plasma; proteomic patterns; proteomics; serum; tandem mass spectrometry ID PHASE PROTEIN MICROARRAYS; INTERSTITIAL CYSTITIS PATIENTS; CATALYZED REPORTER DEPOSITION; HUMAN PLASMA PROTEOME; OVARIAN-CANCER; PROSTATE-CANCER; QUANTITATIVE-ANALYSIS; SIGNAL AMPLIFICATION; CLINICAL PROTEOMICS; COMBINATION THERAPY AB A major goal of the National Cancer Institute is to alleviate patient pain, suffering and death associated with cancer by the year 2015. This goal does not insinuate a cure for cancer, but rather the development of diagnostics and therapeutics that will eventually decrease cancer morbidity and mortality. A part of meeting this goal is to leverage the enormous data-gathering capabilities of proteomic technologies to discover disease-specific biomarkers in serum, plasma, urine, tissues and other biologic samples. The rapid advance in available technologies that have been spurred by the -omics era, has enabled biologic samples to be surveyed for biomarkers in ways never before possible. However, it is not yet clear which specific technologies will be the most successful. Therefore, proteomic laboratories within the National Cancer Institute are taking a multipronged approach to identify disease-specific biomarkers. This review discusses some of these approaches in their context of meeting the National Cancer Institute's 2015 goal. C1 NCI, SAIC Frederick Inc, Lab Proteom & Analyt Technol, Frederick, MD 21702 USA. George Mason Univ, Ctr Appl Proteom & Mol Med, Manassas, VA 20110 USA. RP Veenstra, TD (reprint author), NCI, SAIC Frederick Inc, Lab Proteom & Analyt Technol, POB B,Bldg 469,Room 160, Frederick, MD 21702 USA. EM veenstra@ncifcrf.gov FU NCI NIH HHS [N01-CO-12400] NR 46 TC 20 Z9 21 U1 0 U2 1 PU FUTURE DRUGS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1478-9450 J9 EXPERT REV PROTEOMIC JI Expert Rev. Proteomics PD OCT PY 2005 VL 2 IS 5 BP 693 EP 703 DI 10.1586/14789450.2.5.693 PG 11 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 089YV UT WOS:000240918700014 PM 16209649 ER PT J AU Marino-Ramirez, L Kann, MG Shoemaker, BA Landsman, D AF Marino-Ramirez, Leonardo Kann, Maricel G. Shoemaker, Benjamin A. Landsman, David TI Histone structure and nucleosome stability SO EXPERT REVIEW OF PROTEOMICS LA English DT Review DE chromatin structure; historic variants; nucleosomes ID INACTIVE X-CHROMOSOME; CORE PARTICLE; CHROMATIN FIBER; H2AX PHOSPHORYLATION; ANGSTROM RESOLUTION; MOLECULAR-CLONING; CRYSTAL-STRUCTURE; ACTIVE CHROMATIN; GENE-EXPRESSION; PROTEIN AB Histone proteins play essential structural and functional roles in the transition between active and inactive chromatin states. Although histones have a high degree of conservation due to constraints to maintain the overall structure of the nucleosomal octameric core, variants have evolved to assume diverse roles in gene regulation and epigenetic silencing. Histone variants, post-translational modifications and interactions with chromatin remodeling complexes influence DNA replication, transcription, repair and recombination. The authors review recent findings on the structure of chromatin that confirm previous interparticle interactions observed in crystal structures. C1 Natl Lib Med, NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. Natl Lib Med, NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Marino-Ramirez, L (reprint author), Natl Lib Med, NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, Bldg 38A,Room 6N601,8600 Rockville Pike,MSC 6075, Bethesda, MD 20894 USA. EM marino@ncbi.nlm.nih.gov; kann@ncbi.nlm.nih.gov; shoemake@ncbi.nlm.nih.gov; landsman@ncbi.nlm.nih.gov RI Landsman, David/C-5923-2009; Kann, Maricel/E-5701-2012; Marino-Ramirez, Leonardo/I-5759-2013; OI Marino-Ramirez, Leonardo/0000-0002-5716-8512; Landsman, David/0000-0002-9819-6675 FU Intramural NIH HHS [Z99 LM999999] NR 72 TC 47 Z9 52 U1 2 U2 8 PU FUTURE DRUGS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1478-9450 J9 EXPERT REV PROTEOMIC JI Expert Rev. Proteomics PD OCT PY 2005 VL 2 IS 5 BP 719 EP 729 DI 10.1586/14789450.2.5.719 PG 11 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 089YV UT WOS:000240918700016 PM 16209651 ER PT J AU Hager-Braun, C Tomer, KB AF Hager-Braun, Christine Tomer, Kenneth B. TI Determination of protein-derived epitopes by mass spectrometry SO EXPERT REVIEW OF PROTEOMICS LA English DT Review DE chemical modification; conformational; discontinuous; epitope extraction and excision; ESI-MS; H/D exchange; immunosorption; limited proteolysis; MALDI-MS ID IMMUNODEFICIENCY-VIRUS TYPE-1; DIFFERENTIAL CHEMICAL-MODIFICATION; ANTIBODY-PEPTIDE COMPLEXES; SURFACE-PLASMON RESONANCE; MONOCLONAL-ANTIBODY; ELECTROSPRAY-IONIZATION; LIMITED PROTEOLYSIS; MOLECULAR CHARACTERIZATION; CONFORMATIONAL EPITOPE; DISCONTINUOUS EPITOPE AB Mass spectrometry has evolved as a technique suitable for the characterization of peptides and proteins beyond their linear sequence. The advantages of mass spectrometric sample analysis are high sensitivity, high mass accuracy, rapid analysis time and low sample consumption. In epitope mapping, the molecular structure of an antigen (the epitope or antigenic determinant) that interacts with the paratope (recognition surface) of the antibody is identified. To obtain information on linear, conformational and/or discontinuous epitopes, various approaches have been developed in conjunction with mass spectrometry. These methods include limited proteolysis and epitope footprinting, epitope excision and epitope extraction for linear epitopes and probing the surface accessibility of residues by differential chemical modifications of specific amino acid side chains or by differential hydrogen/deuterium exchange of the protein backbone amides for conformational and discontinuous epitopes. Epitope mapping by mass spectrometry is applicable in basic biochemical research and, with increasing robustness, should soon find its implementation in routine clinical diagnosis. C1 NIEHS, NIH, DHHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. RP Hager-Braun, C (reprint author), NIEHS, NIH, DHHS, Struct Biol Lab, 111 TW Alexander Dr,POB 12233, Res Triangle Pk, NC 27709 USA. EM hagerbr1@niehs.nih.gov; tomer@niehs.nih.gov RI Tomer, Kenneth/E-8018-2013 NR 75 TC 33 Z9 33 U1 0 U2 11 PU FUTURE DRUGS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1478-9450 J9 EXPERT REV PROTEOMIC JI Expert Rev. Proteomics PD OCT PY 2005 VL 2 IS 5 BP 745 EP 756 DI 10.1586/14789450.2.5.745 PG 12 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 089YV UT WOS:000240918700018 PM 16209653 ER PT J AU Fu, JD Li, J Tweedie, D Yu, HM Chen, L Wang, R Riordon, DR Brugh, SA Wang, SQ Boheler, KR Yang, HT AF Fu, JD Li, J Tweedie, D Yu, HM Chen, L Wang, R Riordon, DR Brugh, SA Wang, SQ Boheler, KR Yang, HT TI Crucial role of the sarcoplasmic reticulum in the developmental regulation of Ca2+ transients and contraction in cardiomyocytes derived from embryonic stem cells SO FASEB JOURNAL LA English DT Article DE cardiomyocyte differentiation; calcium transients; type 2 ryanodine receptor ID BETA-ADRENERGIC STIMULATION; CARDIAC MYOCYTES; RYANODINE RECEPTOR; INTRACELLULAR CALCIUM; CHAMBER MYOCARDIUM; MOUSE HEART; RAT; RELEASE; DIFFERENTIATION; CHANNELS AB In adult myocardium, excitation-contraction coupling is critically regulated by sarcoplasmic reticulum (SR) Ca2+ release via type 2 ryanodine receptor (RyR2), but generally, it is believed that SR-function is rudimentary in the fetal heart and in embryonic stem (ES) cell-derived cardiomyocytes (ESCMs), a possible source for cell replacement therapies. This study used wild-type (RyR2(+/+)) and RyR2 null ( RyR2(-/-)) ESCMs as an in vitro model of cardiomyogenesis, together with pharmacological approaches and expression profiles of genes relevant for SR function, to elucidate the functional importance of RyR2 and SR on the regulation of Ca2+ transients and contraction during early cardiomyocyte development. During differentiation of RyR2(+/+) ESCMs, SR function developed progressively with increased basal cytosolic free Ca2+ concentration ([ Ca2+] (i)), enhanced frequency and amplitude, and decreased duration of Ca2+ transients that were inhibited by ryanodine and thapsigargin. These functional traits correlated with SR Ca2+ load and the expression of RyR2, SERCA2a, and phospholamban. RyR2-/- ESCMs, comparatively, demonstrated a significantly prolonged time-to-peak and reduced frequency of Ca2+ transients and contractions. beta-adrenergic stimulation of RyR2(+/+) ESCMs increased the frequency and amplitude of Ca2+ transients with differentiation but was much weaker in RyR2(-/-)ESCMs. We conclude that functional SR and control of RyR2-mediated SR Ca2+ release directly contribute to the spontaneous and beta-adrenergic receptor-stimulated contraction of ESCMs, even at very immature stages of development. C1 Chinese Acad Sci, Mol Cardiol Lab, Inst Hlth Sci, SIBS, Shanghai 200025, Peoples R China. Shanghai Jiao Tong Univ, Sch Med, Shanghai 200025, Peoples R China. Chinese Acad Sci, Key Lab Stem Cell Biol, SIBS, Shanghai 200025, Peoples R China. Chinese Acad Sci, Grad Sch, Shanghai 200025, Peoples R China. NIA, Cardiovasc Sci Lab, Baltimore, MD 21224 USA. Peking Univ, Coll Life Sci, Natl Key Lab Biomembrane & Membrane Biotechnol, Beijing 100871, Peoples R China. RP Yang, HT (reprint author), Chinese Acad Sci, Mol Cardiol Lab, Inst Hlth Sci, SIBS, 225 Chong Qing Nan Rd,1 Bulg, Shanghai 200025, Peoples R China. EM htyang@sibs.ac.cn RI Fu, Jidong/E-8173-2012 NR 38 TC 4 Z9 4 U1 0 U2 13 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 2005 VL 19 IS 12 BP 181 EP + DI 10.1096/fj.05-4501fje PG 21 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 980CI UT WOS:000232991100007 ER PT J AU Iribarren, P Chen, KQ Hu, JY Gong, WH Cho, EH Lockett, S Uranchimeg, B Wang, JM AF Iribarren, P Chen, KQ Hu, JY Gong, WH Cho, EH Lockett, S Uranchimeg, B Wang, JM TI CpG-containing oligodeoxynucleotide promotes microglial cell uptake of amyloid beta 1-42 peptide by up-regulating the expression of the G-protein-coupled receptor mFPR2 SO FASEB JOURNAL LA English DT Article DE Alzheimer's disease; chemotaxis; inflammation; phagocytosis; TLR9 ID AMYLOID-BETA-PROTEIN; TOLL-LIKE RECEPTOR-9; ANTI-DNA ANTIBODIES; ALZHEIMERS-DISEASE; SCAVENGER RECEPTOR; BACTERIAL-DNA; GENE-THERAPY; MOUSE MODEL; B-CELLS; ACTIVATION AB Human G protein-coupled formyl peptide receptor like 1 (FPRL1) and its mouse homologue murine formyl peptide receptor 2 (mFPR2) mediate the chemotactic activity of amyloid beta 1-42 (A beta(42)), a key pathogenic peptide in Alzheimer's disease ( AD). Since mFPR2 is up-regulated in mouse microglia by lipopolysaccharide (LPS), a Toll-like receptor 4 ligand, we investigated the capacity of CpG-containing oligodeoxynucleotide (ODN), a Toll-like receptor (TLR) 9 ligand, to regulate the expression of mFPR2 in mouse microglia. CpG ODN markedly enhanced the expression and function of mFPR2 in microglial cells, which exhibited increased chemotactic responses to mFPR2 agonists, including A beta(42). The effect of CpG ODN is dependent on activation of p38 MAPK. Further studies showed that CpG ODN-treated microglia increased their capacity to endocytose A beta(42) through mFPR2, as this process was abrogated by pertussis toxin, a Gi protein inhibitor, and W peptide, another potent mFPR2 agonist. Our results suggest that TLR9 may play an important role in promoting microglial recognition of A beta(42), thus affecting the pathogenic process of AD. C1 NCI, Mol Immunoregulat Lab, Canc Res Ctr, Frederick, MD 21702 USA. SAIC Frederick, Basic Res Program, Frederick, MD 21702 USA. SAIC Frederick, Image Anal Lab, Frederick, MD 21702 USA. SAIC Frederick, Dev Therapeut Program, Tumor Hypoxia Program, Frederick, MD 21702 USA. RP Wang, JM (reprint author), NCI, Mol Immunoregulat Lab, Canc Res Ctr, Bldg 560,Room 31-40, Frederick, MD 21702 USA. EM wangji@mail.ncifcrf.gov FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 61 TC 51 Z9 52 U1 1 U2 4 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD OCT PY 2005 VL 19 IS 12 BP 2032 EP + DI 10.1096/fj.05-45758fje PG 19 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 980CI UT WOS:000232991100022 PM 16219804 ER PT J AU In, Y Minoura, K Tomoo, K Sasaki, Y Lazarus, LH Okada, Y Ishida, T AF In, Y Minoura, K Tomoo, K Sasaki, Y Lazarus, LH Okada, Y Ishida, T TI Structural function of C-terminal amidation of endomorphin SO FEBS JOURNAL LA English DT Article DE endomorphin-2; C-terminal-deaminated endomorphin-2; NMR; molecular calculation; X-ray crystal analysis ID MU-OPIOID RECEPTOR; CONFORMATIONAL-ANALYSIS; DISTANCE GEOMETRY; AGONIST; POTENT; BINDING; ACID; SPECTROSCOPY; ENKEPHALIN; PEPTIDES AB To investigate the structural function of the C-terminal amide group of endomorphin-2 (EM2, H-Tyr-Pro-Phe-Phe-NH2), an endogenous mu-opioid receptor ligand, the solution conformations of EM2 and its C-terminal free acid (EM2OH, H-Tyr-Pro-Phe-Phe-OH) in TFE (trifluoroethanol), water (pH 2.7 and 5.2), and aqueous DPC (dodecylphosphocholine) micelles (pH 3.5 and 5.2) were investigated by the combination of 2D H-1-NMR measurement and molecular modelling calculation. Both peptides were in equilibrium between the cis and trans rotamers around the Tyr-Pro w bond with population ratios of 1 : 1 to 1 : 2 in dimethyl sulfoxide, TFE and water, whereas they predominantly took the trans rotamer in DPC micelle, except in EM2OH at pH 5.2, which had a trans/cis rotamer ratio of 2 : 1. Fifty possible 3D conformers were generated for each peptide, taking different electronic states depending on the type of solvent and pH (neutral and monocationic forms for EM2, and zwitterionic and monocation forms for EM2OH) by the dynamical simulated annealing method, under the proton-proton distance constraints derived from the ROE cross-peak intensities. These conformers were then roughly classified into four groups of two open [reverse S (rS)- and numerical 7 (n7)-type] and two folded (F1- and F2-type) conformers according to the conformational pattern of the backbone structure. Most EM2 conformers in neutral (in TFE) and monocationic (in water and DPC micelles) forms adopted the open structure (mixture of major rS-type and minor n7-type conformers) despite the trans/cis rotamer form. On the other hand, the zwitterionic EM2OH in TFE, water and DPC micelles showed an increased population of F1- and F2-type folded conformers, the population of which varied depending on their electronic state and pH. Most of these folded conformers took an F1-type structure similar to that stabilized by an intramolecular hydrogen bond of (Tyr1)NH3+...COO-(Phe4), observed in its crystal structure. These results show that the substitution of a carboxyl group for the C-terminal amide group makes the peptide structure more flexible and leads to the ensemble of folded and open conformers. The conformational requirement of EM2 for binding to the mu-opioid receptor and the structural function of the C-terminal amide group are discussed on the basis of the present conformational features of EM2 and EM2OH and a possible model for binding to the mu-opioid receptor, constructed from the template structure of rhodopsin. C1 Osaka Univ Pharmaceut Sci, Osaka 5691094, Japan. Tohoku Pharmaceut Univ, Dept Biochem, Sendai, Miyagi, Japan. Natl Inst Environm Hlth Sci, Med Chem Grp, Lab Pharmacol & Chem, Res Triangle Pk, NC USA. Kobe Gakuin Univ, Fac Pharmaceut Sci, Kobe, Hyogo 65121, Japan. RP In, Y (reprint author), Osaka Univ Pharmaceut Sci, 4-20-1 Nasahara, Osaka 5691094, Japan. NR 31 TC 28 Z9 28 U1 0 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1742-464X J9 FEBS J JI FEBS J. PD OCT PY 2005 VL 272 IS 19 BP 5079 EP 5097 DI 10.1111/j.1742-4658.2005.04919.x PG 19 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 965LE UT WOS:000231951200022 PM 16176278 ER PT J AU Altschul, SF Wootton, JC Gertz, EM Agarwala, R Morgulis, A Schaffer, AA Yu, YK AF Altschul, SF Wootton, JC Gertz, EM Agarwala, R Morgulis, A Schaffer, AA Yu, YK TI Protein database searches using compositionally adjusted substitution matrices SO FEBS JOURNAL LA English DT Article; Proceedings Paper CT 15th Biennial Conference on Methods in Protein Structure Analysis CY AUG 29-SEP 02, 2004 CL Seattle, WA SP Int Assoc Protein Structure Anal & Proteom DE BLAST; BLOSUM; compositional adjustment; protein database searches; substitution matrices ID AMINO-ACID-SEQUENCES; BIOLOGICAL SEQUENCES; SCORING MATRIX; PSI-BLAST; CLASSIFICATION; DISTRIBUTIONS; REPLACEMENT; STATISTICS; COMPLEXITY; GENERATION AB Almost all protein database search methods use amino acid substitution matrices for scoring, optimizing, and assessing the statistical significance of sequence alignments. Much care and effort has therefore gone into constructing substitution matrices, and the quality of search results can depend strongly upon the choice of the proper matrix. A long-standing problem has been the comparison of sequences with biased amino acid compositions, for which standard substitution matrices are not optimal. To address this problem, we have recently developed a general procedure for transforming a standard matrix into one appropriate for the comparison of two sequences with arbitrary, and possibly differing compositions. Such adjusted matrices yield, on average, improved alignments and alignment scores when applied to the comparison of proteins with markedly biased compositions. Here we review the application of compositionally adjusted matrices and consider whether they may also be applied fruitfully to general purpose protein sequence database searches, in which related sequence pairs do not necessarily have strong compositional biases. Although it is not advisable to apply compositional adjustment indiscriminately, we describe several simple criteria under which invoking such adjustment is on average beneficial. In a typical database search, at least one of these criteria is satisfied by over half the related sequence pairs. Compositional substitution matrix adjustment is now available in NCBI's protein-protein version of BLAST. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Altschul, SF (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM altschul@ncbi.nlm.nih.gov RI Schaffer, Alejandro/F-2902-2012; OI Gertz, E. Michael/0000-0001-8390-4387 FU NLM NIH HHS [Z01 LM000072-10] NR 42 TC 389 Z9 398 U1 4 U2 30 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1742-464X J9 FEBS J JI FEBS J. PD OCT PY 2005 VL 272 IS 20 BP 5101 EP 5109 DI 10.1111/j.1742-4658.2005.04945.x PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 972FE UT WOS:000232438800002 PM 16218944 ER PT J AU Bakalov, VK Anasti, JN Calis, KA Vanderhoof, VH Premkumar, A Chen, S Furmaniak, J Smith, BR Merino, MJ Nelson, LM AF Bakalov, VK Anasti, JN Calis, KA Vanderhoof, VH Premkumar, A Chen, S Furmaniak, J Smith, BR Merino, MJ Nelson, LM TI Autoimmune oophoritis as a mechanism of follicular dysfunction in women with 46,XX spontaneous premature ovarian failure SO FERTILITY AND STERILITY LA English DT Article DE adrenal cortex autoantibodies; autoimmune oophoritis; premature ovarian failure; hypergonadotropic amenorrhea; hypergonadotropic hypogonadism; ovarian insufficiency; adrenal insufficiency; Addison disease ID STEROID 21-HYDROXYLASE AUTOANTIBODIES; ADDISONS-DISEASE; SECONDARY AMENORRHEA; NATURAL-HISTORY; ADRENAL-CORTEX; YOUNG-WOMEN; ANTIBODIES; IMMUNOFLUORESCENCE; IDENTIFICATION; INFERTILITY AB Objective: To assess the association between serum adrenal cortex autoantibodies and histologically confirmed autoimmune lymphocytic oophoritis. Design: Controlled, prospective. Setting: Tertiary research center. Patient(s): Two hundred sixty-six women with 46,XX spontaneous premature ovarian failure. Intervention(s): Ovarian biopsy in 10 women. Main Outcome Measure(s): Serum adrenal cortex autoantibodies assessed by indirect immunofluorescence and autoimmune oophoritis assessed by immunohistochemical lymphocyte markers. Result(s): We obtained a histologic diagnosis of autoimmune oophoritis in four women who tested positive for adrenal cortex autoantibodies and excluded this diagnosis in ovarian biopsies from six women who tested negative for adrenal cortex autoantibodies (4/4 vs. 0/6). Women with histologically confirmed autoimmune oophoritis had a greater total ovarian volume as assessed by transvaginal sonography (11.4 +/- 5.6 mL vs. 1.5 +/- 0.4 mL) (mean +/- SEM). They were also more likely to have subclinical adrenal insufficiency and clinical signs of androgen deficiency (3/4 vs. 0/6). Overall, 10/266 women tested positive for adrenal cortex autoantibodies (3.8%, 95% confidence interval: 1.8%-6.5%). Conclusion(s): In, women who present with 46,XX spontaneous premature ovarian,failure as their primary concern there is a clear association between serum adrenal cortex autoantibodies and the presence of histologiically confirmed autoimmune oophoritis. (Fertil Sterilg (R) 2005;84:958-65. (c) 2005 by American Society for Reproductive Medicine.) C1 NICHHD, Sect Womens Hlth Res, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NCI, Clin Res Ctr, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RSR Ltd, FIRS Labs, Cardiff, Wales. RP Nelson, LM (reprint author), NICHHD, Sect Womens Hlth Res, Dev Endocrinol Branch, NIH, CRC 1-3330,10 Ctr Dr,MSC-1103, Bethesda, MD 20892 USA. EM Lawrence_Nelson@nih.gov FU Intramural NIH HHS NR 47 TC 68 Z9 69 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD OCT PY 2005 VL 84 IS 4 BP 958 EP 965 DI 10.1016/j.fertnstert.2005.04.060 PG 8 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 973SD UT WOS:000232542000022 PM 16213850 ER PT J AU Feinberg, EC Molitch, ME Endres, LK Peaceman, AM AF Feinberg, EC Molitch, ME Endres, LK Peaceman, AM TI The incidence of Sheehan's syndrome after obstetric hemorrhage SO FERTILITY AND STERILITY LA English DT Article; Proceedings Paper CT 60th Annual Meeting of the American-Society-for-Reproductive-Medicine CY OCT 16-20, 2004 CL Philadelphia, PA SP Amer Soc Reprod Med DE hypopituitarism; postpartum hemorrhage; menstrual dysfunction; lactation difficulty; secondary infertility ID PITUITARY; NECROSIS; ADULTS AB Objective: To estimate the incidence of Sheehan's syndrome in a well-described cohort of patients with obstetric hemorrhage. Design: Retrospective cohort study. Setting: Tertiary care center. Patient(s): Two hundred patients. Intervention(s): Questionnaires were sent to study and comparison patients asking about menstrual dysfunction, lactation difficulty, cold intolerance, fatigue, axillary and pubic hair loss, and secondary infertility. Main Outcome Measure(s): Women who experienced two or more symptoms were referred for hormone testing of insulin-like growth factor I (IGF-1), T-4, PRL, and early morning cortisol (F) levels. Result(s): A total of 109 patients responded to the survey, a 55% response rate, Fourteen of 55 (25%) patients in the hemorrhage group identified themselves as suffering from two or more symptoms on the questionnaire. Eight of the 14 patients were tested, but none had hormonal evidence of hypopituitarism. Four of 54 (7%) comparison patients also identified themselves as suffering from two or more symptoms, but neither of the two tested had hormonal evidence of hypopituitarism. Conclusion(s): Among women with postpartum hemorrhage, subsequent development of clinical symptoms does not correlate well with laboratory evidence of hypopituitarism. Clinically significant Sheehan syndrome is an uncommon consequence of obstetric hemorrhage in today's environment. (Fertil Steril (R) 2005;84:975-9. (c) 2005 by American Society for Reproductive Medicine.) C1 NW Mem Hosp, Feinberg Sch Med, Dept Obstet & Gynecol, Chicago, IL 60611 USA. NW Mem Hosp, Feinberg Sch Med, Dept Endocrinol, Chicago, IL 60611 USA. RP Feinberg, EC (reprint author), NICHD, RBMB, NIH, CFC, Bld 10,Rm 1-3140,10 Ctr Dr, Bethesda, MD 20892 USA. EM feinbere@mail.nih.gov OI Peaceman, Alan/0000-0002-4515-4850 NR 12 TC 19 Z9 20 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 2005 VL 84 IS 4 BP 975 EP 979 DI 10.1016/j.fertnstert.2005.04.034 PG 5 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 973SD UT WOS:000232542000024 PM 16213852 ER PT J AU Neithardt, AB Segars, JH McKeeby, JL AF Neithardt, AB Segars, JH McKeeby, JL TI Refining embryo transfer - Reply to the authors SO FERTILITY AND STERILITY LA English DT Letter ID TRANSFER CATHETER C1 NICHHD, Reprod Biol & Med Branch, NIH, Bethesda, MD 20892 USA. Shady Grove Fertil Reprod Sci Ctr, Rockville, MD USA. RP Neithardt, AB (reprint author), NICHHD, Reprod Biol & Med Branch, NIH, Bethesda, MD 20892 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD OCT PY 2005 VL 84 IS 4 BP 1056 EP 1057 DI 10.1016/j.fertnstert.2005.06.008 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 973SD UT WOS:000232542000043 ER PT J AU Liu, G Martins, IH Chiorini, JA Davidson, BL AF Liu, G Martins, IH Chiorini, JA Davidson, BL TI Adeno-associated virus type 4 (AAV4) targets ependyma and astrocytes in the subventricular zone and RMS SO GENE THERAPY LA English DT Article DE adeno-associated virus type 4 (AAV4); neurogenesis; ependyma; subventricular zone; astrocytes; radial glia; rostral migratory stream ID NEURAL STEM-CELLS; CENTRAL-NERVOUS-SYSTEM; ADULT MAMMALIAN BRAIN; ROSTRAL MIGRATORY STREAM; PROGENITOR CELLS; MOUSE BRAIN; RADIAL GLIA; GENE DELIVERY; NEUROGENESIS; FOREBRAIN AB The subventricular zone (SVZ) is one of the neurogenic niches in the adult mammalian brain. The SVZ is of interest for studies on neurogenesis and stem cell therapy. Here, we report specific transduction of ependyma and/or astrocytes by recombinant adeno-associated virus type 4 (AAV4) viral vectors. AAV4 vectors encoding beta-galactosidase or eGFP were injected into the lateral ventricles of neonatal and adult C57BL/6 mouse brains. In addition, SVZ injections were conducted on adult mice. AAV4 vectors show a characteristic transduction of the ependyma independent of delivery route. However, AAV4 virus injected into the SVZ targeted GFAP positive astrocytes forming the glial tube in the SVZ and rostral migratory stream (RMS). Our results introduce AAV4 as a new tool by which to manipulate glial cells in the RMS. C1 Univ Iowa, Program Gene Therapy, Iowa City, IA 52242 USA. Univ Iowa, Dept Internal Med, Iowa City, IA 52242 USA. Univ Iowa, Dept Neurol, Iowa City, IA 52242 USA. Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. Univ Iowa, Dept Physiol & Biophys, Iowa City, IA 52242 USA. RP Davidson, BL (reprint author), Univ Iowa, Program Gene Therapy, 200 EMRB, Iowa City, IA 52242 USA. FU NICHD NIH HHS [HD 33531] NR 29 TC 36 Z9 37 U1 0 U2 4 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 2005 VL 12 IS 20 BP 1503 EP 1508 DI 10.1038/sj.gt.3302554 PG 6 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 970NW UT WOS:000232317900004 PM 15944733 ER PT J AU Dong, HF Wigmore, K Carrington, MN Dean, M Turpin, JA Howard, OMZ AF Dong, HF Wigmore, K Carrington, MN Dean, M Turpin, JA Howard, OMZ TI Variants of CCR5, which are permissive for HIV-1 infection, show distinct functional responses to CCL3, CCL4 and CCL5 SO GENES AND IMMUNITY LA English DT Article DE chemokine receptor; CCR5; HIV-1; desensitization ID CHEMOKINE RECEPTOR CCR5; IMMUNODEFICIENCY-VIRUS TYPE-1; MULTIPLE-SCLEROSIS; LIGAND-BINDING; CCR5-DELTA-32 MUTATION; RHEUMATOID-ARTHRITIS; TRANSMEMBRANE DOMAIN; GENETIC-VARIATION; IMMUNE-RESPONSE; TERMINAL DOMAIN AB CCR5 is one of the primary coreceptors for Env-mediated fusion between cells and human immunodeficiency virus type 1 (HIV-1). Analyses of CCR5 variants in cohorts of HIV-1 high-risk individuals led to the identification of multiple single amino-acid substitutions, which may have functional consequences. This study focused on eight naturally occurring allelic variants located between amino-acid residues 60 and 334 of CCR5. All studied allelic variants were highly expressed on the cell surface of HEK-293 cells and permissive for HIV-1 infection. Variant G301V showed 3.5-fold increase in 50% effective concentration (EC50) for CCL4 (MIP 1beta) in a competitive binding assay. There was also a significant reduction in CCL5 ( RANTES) EC50 for the R223Q, A335V and Y339F variants. The most unexpected functional abnormality was exhibited by the R60S variant that exhibited a loss of ligand-induced desensitization in chemotaxis assays, but showed normal CCL4 and CCL5 binding avidity. This mutation is located in the first intracellular loop, a domain that has not previously been shown to be involved in receptor desensitization. In conclusion, our results support earlier studies showing that these naturally occurring point mutations do not limit HIV-1 infection, and indicated that single amino-acid changes can have unexpected functional consequences. C1 NCI, CCR, Lab Mol Immunoregulat, Frederick, MD 21702 USA. RP Howard, OMZ (reprint author), NCI, CCR, Lab Mol Immunoregulat, POB B,1050 Boyles St, Frederick, MD 21702 USA. EM howardz@mail.ncifcrf.gov RI Dean, Michael/G-8172-2012; Howard, O M Zack/B-6117-2012 OI Dean, Michael/0000-0003-2234-0631; Howard, O M Zack/0000-0002-0505-7052 FU NCI NIH HHS [N01-CO-12400, N01CO12400, Z01 BC005652-15] NR 64 TC 8 Z9 9 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1466-4879 J9 GENES IMMUN JI Genes Immun. PD OCT PY 2005 VL 6 IS 7 BP 609 EP 619 DI 10.1038/sj.gene.6364247 PG 11 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 978OB UT WOS:000232881800007 PM 16015368 ER PT J AU Perdigao, PF Stergiopoulos, SG De Marco, L Matyakhina, L Boikos, SA Gomez, RS Pimenta, FJGS Stratakis, CA AF Perdigao, PF Stergiopoulos, SG De Marco, L Matyakhina, L Boikos, SA Gomez, RS Pimenta, FJGS Stratakis, CA TI Molecular and immunohistochemical investigation of protein kinase a regulatory subunit type Ia (PRKARIA) in odontogenic myxomas SO GENES CHROMOSOMES & CANCER LA English DT Article ID SPORADIC CARDIAC MYXOMAS; GS-ALPHA GENE; CARNEY COMPLEX; ENDOCRINE OVERACTIVITY; ACTIVATING MUTATIONS; RI-ALPHA; FEATURES; PIGMENTATION; EXPRESSION; LESIONS AB Odontogenic myxomas are rare benign neoplasms affecting the jaw. Myxomas of bones and other sites occur as part of Carney complex (CNC), a multiple neoplasia syndrome caused by mutations in the PRKARlA gene, which codes for the regulatory subunit of protein kinase A (PKA). In the present study, 17 odontogenic myxomas from patients without CNC were screened for PRKARlA mutations and PRKARlA protein expression by immunohistochernistry (IHC). Mutations of the coding region of the PRKARlA gene were identified in 2 tumors; both these lesions showed no or significantly decreased immunostaining of PRKARlA in the tumor compared to that in the surrounding normal tissue. One mutation (c.725C > A) led to a nonconservative amino acid substitution in a highly conserved area of the gene (A213D); the other was a single base-pair deletion that led to a frameshift (del774C) and a stop codon I I amino acids downstream of the mutation site; both tumors were heterozygous for the respective mutations. Of the remaining tumors, 7 of the 15 without mutations showed almost no PRKARlA in the tumor cells, whereas IHC showed that the protein was abundant in nontumorous cells. We concluded that PRKARlA may be involved by its down-regulation in the pathogenesis of odontogenic myxomas caused by mutations and/or other genetic mechanisms. Of the sporadic, nonfamilial tumors associated with PRKARlA mutations, the odontogenic type was the first myxomatous lesion found to harbor somatic PRKARlA sequence changes. Published 2005 Wiley-Liss, Inc. C1 Univ Fed Minas Gerais, Dept Pharmacol, Belo Horizonte, MG, Brazil. Univ Fed Minas Gerais, Dept Oral Surg & Pathol, Belo Horizonte, MG, Brazil. NICHD, Sect Endocrinol & Genet, DEB, NIH, Bethesda, MD 20892 USA. RP Stratakis, CA (reprint author), NICHD, Sect Endocrinol & Genet, DEB, NIH, Bldg 10,CRC,Room 1-3330,10 Ctr Dr,MSC 1103, Bethesda, MD 20892 USA. EM stratakc@mail.nih.gov RI De Marco, Luiz /H-6275-2012; PERDIGAO, PAOLLA /M-7481-2014; Gomez, Ricardo/G-1976-2012 OI Gomez, Ricardo/0000-0001-8770-8009 NR 33 TC 14 Z9 15 U1 0 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD OCT PY 2005 VL 44 IS 2 BP 204 EP 211 DI 10.1002/gcc.20232 PG 8 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 957DG UT WOS:000231349100010 PM 16001434 ER PT J AU Zaykin, DV Zhivotovsky, LA AF Zaykin, DV Zhivotovsky, LA TI Ranks of genuine associations in whole-genome scans SO GENETICS LA English DT Article ID FALSE-POSITIVE PEAKS; LINKAGE DISEQUILIBRIUM; GENETIC ASSOCIATION; COMPLEX TRAITS; DISCOVERY RATE; SUSCEPTIBILITY; DISEASE; DISSECTION; HAPLOTYPES; SELECTION AB With the recent advances in high-throughput genotyping techniques, it is now possible to perform whole-genome association studies to fine map causal polymorphisms underlying important traits that influence susceptibility to human diseases and efficacy of drugs. Once a genome scan is completed the results can be sorted by the association statistic value. What is the probability that true positives will be encountered among the first most associated markers? When a particular polymorphism is found associated with the trait, there is a chance that it represents either a "true" or a "false" association (TA vs. FA). Setting appropriate significance thresholds has been considered to provide assurance of sufficient odds that the associations found to be significant are genuine. However, the problem with genome scans involving thousands of markers is that the statistic values of FAs can reach quite extreme magnitudes. In Such situations, the distributions corresponding to TAs and the most extreme FAs become comparable and significance thresholds tend to penalize TAs and FAs in a similar fashion. When sorting between true and false associations, the "typical" place (i.e., rank) of TAs among the most significant outcomes becomes important, ordered by the association statistic value. The distribution of ranks that we study here allows calculation of several useful quantities. In particular, it gives the number of most significant markers needed for a follow-up study to guarantee that a true association is included with certain probability. This can be calculated conditionally on having applied a multiple-testing correction. Effects of multilocus (e.g., haplotype association) tests and impact of linkage disequilibrium On the distribution of ranks associated with TAs are evaluated and can be taken into account. C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. Russian Acad Sci, NI Vavilov Gen Genet Inst, Moscow 117809, Russia. RP Zaykin, DV (reprint author), NIEHS, NIH, MD A3-03,S Campus Bldg 101,POB 12233, Res Triangle Pk, NC 27709 USA. EM zaykind@niehs.nih.gov NR 32 TC 57 Z9 60 U1 0 U2 1 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD OCT PY 2005 VL 171 IS 2 BP 813 EP 823 DI 10.1534/genetics.105.044206 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 982XF UT WOS:000233194500034 PM 16020784 ER PT J AU Bi, XL Gong, M Srikanta, D Rong, YS AF Bi, XL Gong, M Srikanta, D Rong, YS TI Drosophila ATM and Mre11 are essential for the G(2)/M checkpoint induced by low-dose irradiation SO GENETICS LA English DT Article ID DNA-DAMAGE; ATAXIA-TELANGIECTASIA; TELOMERE MAINTENANCE; ACTIVATION; STABILITY; MEI-41; GENE AB Others have suggested recently that the conserved ATM checkpoint kinase is minimally involved in controlling the G(2)/M checkpoint in Drosophila that serves to prevent mitotic entry in the presence of DNA damage. Our data indicate that both ATM and its regulator Mre11 are important for the checkpoint and that their roles become essential when animals are challenged with a low dose of X rays or when they have compromised checkpoint function of the ATM-related ATR kinase. C1 NCI, Mol Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Rong, YS (reprint author), NCI, Mol Cell Biol Lab, NIH, Bldg 37,Room 6050,37 Convent Dr, Bethesda, MD 20892 USA. EM rongy@mail.nih.gov RI Bi, Xiaolin/E-7469-2010; rong, yikang/G-6179-2011; Bi, Xiaolin/C-7038-2014 OI Bi, Xiaolin/0000-0002-7172-7851; Bi, Xiaolin/0000-0003-2837-9457 FU Intramural NIH HHS NR 18 TC 21 Z9 23 U1 0 U2 2 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD OCT PY 2005 VL 171 IS 2 BP 845 EP 847 DI 10.1534/genetics.105.047720 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 982XF UT WOS:000233194500039 PM 16020777 ER PT J AU Anderson, RT Press, N Tucker, DC Snively, BM Wenzel, L Ellis, SD Hall, MA Walker, AP Thomson, EJ Lewis-Jack, O Acton, RT AF Anderson, RT Press, N Tucker, DC Snively, BM Wenzel, L Ellis, SD Hall, MA Walker, AP Thomson, EJ Lewis-Jack, O Acton, RT TI Patient acceptability of genotypic testing for hemochromatosis in primary care SO GENETICS IN MEDICINE LA English DT Article ID HEALTH SURVEY SF-36; HEREDITARY HEMOCHROMATOSIS; CANCER SUSCEPTIBILITY; PSYCHOLOGICAL IMPACT; OVARIAN-CANCER; HIGH-RISK; BRCA1; BREAST; DISTRESS; FAMILIES AB Purpose: Genetic screening can enable timely detection and treatment of hereditary hemochromatosis (HH). Little is known about patient acceptability of DNA testing as compared to conventional phenotypic testing. Methods: Within the HEIRS Study, a large primary-care screening study of HH and iron overload, we randomly assigned participants to receive brief information on either HH genotypic or phenotypic testing, and assessed the willingness to accept this test. The study was designed to recruit an equal number of African Americans and Caucasians. Results: A total of 2500 participants were recruited from waiting rooms of primary care practices; 2165 participants who self-identified as African Americans and Caucasians were included in the analyses. Overall, 56% had accepted a genotypic test versus 58% for a phenotypic test. Adjusting for Field Center (FC), age, gender, race, educational attainment, global health rating, and knowledge of the test, the odds ratio of accepting a genotypic versus phenotypic test was 0.85 (95% CI: 0.71, 1.02; P = 0.078). Characteristics associated with test acceptance were age 45-64 years, female gender, Caucasian race, self-rated health less than "very good", and knowledge of the test. Test acceptance was associated with interest in knowing more about health (81%) and in helping family members (71%). Refusal reasons included a need to talk with a doctor (44%), concern about privacy (32%), and dislike of blood drawing (29%). Conclusion: In this diverse sample of primary care patients, stated acceptance of genotypic testing for HH mutations was similar to phenotypic testing for blood iron. Patient education regarding the nature of test, importance of disease detection, and privacy protection appear to be essential for achieving high rates of screening participation. C1 Wake Forest Univ, Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27157 USA. Kaiser Permanente Ctr Hlth Res, Portland, OR USA. Univ Alabama, Dept Psychol, Birmingham, AL 35294 USA. Univ Calif Irvine, Dept Med, Div Epidemiol, Irvine, CA USA. Univ Calif Irvine, Dept Pediat, Div Human Genet, Irvine, CA 92717 USA. NHGRI, Bethesda, MD 20892 USA. Howard Univ, Dept Psychol, Washington, DC 20059 USA. Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA. RP Anderson, RT (reprint author), Wake Forest Univ, Sch Med, Dept Publ Hlth Sci, Med Ctr Blvd, Winston Salem, NC 27157 USA. RI Ellis, Shellie/I-4811-2015 OI Ellis, Shellie/0000-0002-3599-0804 FU NCRR NIH HHS [M01-RR10284, M01-RR00827]; NHLBI NIH HHS [N01-HC05185, N01-HC05188, N01-HC05191, N01-HC05190, N01-HC05192, N01-HC05186, N01-HC05189] NR 40 TC 19 Z9 19 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1098-3600 J9 GENET MED JI Genet. Med. PD OCT PY 2005 VL 7 IS 8 BP 557 EP 563 DI 10.1097/01.GIM.0000177531.53338.65 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 979WB UT WOS:000232974600005 PM 16247294 ER PT J AU Giardine, B Riemer, C Hardison, RC Burhans, R Elnitski, L Shah, P Zhang, Y Blankenberg, D Albert, I Taylor, J Miller, W Kent, WJ Nekrutenko, A AF Giardine, B Riemer, C Hardison, RC Burhans, R Elnitski, L Shah, P Zhang, Y Blankenberg, D Albert, I Taylor, J Miller, W Kent, WJ Nekrutenko, A TI Galaxy: A platform for interactive large-scale genome analysis SO GENOME RESEARCH LA English DT Article ID RETRIEVAL TOOL; IDENTIFICATION; RESOURCES; SEQUENCES; PROMOTERS; ELEMENTS; DATABASE; BROWSER; SCORES; GENE AB Accessing and analyzing the exponentially expanding genomic sequence and functional data pose a challenge for biomedical researchers. Here we describe ail interactive system, Galaxy, that combines the power of existing genome annotation databases with a simple Web portal to enable users to search remote resources, combine data from independent queries, and Visualize the results. The heart of Galaxy is a flexible history system that stores the queries from each user; performs operations Such as intersections, unions, and Subtractions; and links to other computational tools. Galaxy call be accessed at http://g2.bx.psu.edu. C1 Penn State Univ, Huck Inst Life Sci, Ctr Comparat Genom & Bioinformat, University Pk, PA 16802 USA. NHGRI, Bethesda, MD 20892 USA. Univ Calif Santa Cruz, Dept Comp Sci & Engn, Santa Cruz, CA 95064 USA. RP Nekrutenko, A (reprint author), Penn State Univ, Huck Inst Life Sci, Ctr Comparat Genom & Bioinformat, University Pk, PA 16802 USA. EM anton@bx.psu.edu RI Hardison, Ross/G-1142-2010; Giardine, Belinda/A-1599-2010; Phelps, Steve/H-2263-2011; Taylor, James/F-1026-2011; OI Hardison, Ross/0000-0003-4084-7516; Taylor, James/0000-0001-5079-840X; Nekrutenko, Anton/0000-0002-5987-8032 FU NHGRI NIH HHS [HG02238, R01 HG002238]; NIDDK NIH HHS [DK65806, R01 DK065806, R56 DK065806] NR 22 TC 939 Z9 952 U1 4 U2 55 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD OCT PY 2005 VL 15 IS 10 BP 1451 EP 1455 DI 10.1101/gr.4086505 PG 5 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 972EL UT WOS:000232436800017 PM 16169926 ER PT J AU Murphy, WJ Agarwala, R Schaffer, AA Stephens, R Smith, C Crumpler, NJ David, VA O'Brien, SJ AF Murphy, WJ Agarwala, R Schaffer, AA Stephens, R Smith, C Crumpler, NJ David, VA O'Brien, SJ TI A rhesus macaque radiation hybrid map and comparative analysis with the human genome SO GENOMICS LA English DT Article DE rhesus macaque; radiation hybrid map; human genome; chromosome evolution; segmental duplication ID SEGMENTAL DUPLICATIONS; EVOLUTIONARY HISTORY; MOUSE; REARRANGEMENTS; CHROMOSOMES; PRIMATES; BREAKPOINT; KARYOTYPE; SEQUENCES; REVEALS AB The genomes of nonhuman primates are powerful references for better understanding the recent evolution of the human genome. Here we compare the order of 802 genomic markers mapped in a rhesus macaque (Macaca mulatta) radiation hybrid panel with the human genome, allowing for nearly complete cross-reference to the human genome at an average resolution of 3.5 Mb. At least 23 large-scale chromosomal rearrangements, mostly inversions, are needed to explain the changes in marker order between human and macaque. Analysis of the breakpoints flanking inverted chromosomal segments and estimation of their duplication divergence dates provide additional evidence implicating segmental duplications as a major mechanism of chromosomal rearrangement in recent primate evolution. Published by Elsevier Inc. C1 NCI, Basic Res Lab, SAIC Frederick Inc, Lab Genom Divers, Frederick, MD 21702 USA. NIH, Natl Lib Med, NCBI, IEB,Dept Hlth & Human Serv, Bethesda, MD 20894 USA. NIH, Natl Lib Med, NCBI, CBB,Dept Hlth & Human Serv, Bethesda, MD 20894 USA. NCI, Adv Biomed Comp Ctr, Frederick, MD 21702 USA. RP Murphy, WJ (reprint author), Texas A&M Univ, Coll Vet Med & Biomed Sci, Dept Vet Integrat Biosci, Mail Stop 4458, College Stn, TX 77843 USA. EM wmurphy@cvm.tamu.edu RI Schaffer, Alejandro/F-2902-2012 NR 38 TC 23 Z9 23 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 0888-7543 J9 GENOMICS JI Genomics PD OCT PY 2005 VL 86 IS 4 BP 383 EP 395 DI 10.1016/j.ygeno.2005.05.013 PG 13 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 967WR UT WOS:000232122400001 PM 16039092 ER PT J AU Cappola, A Xue, Q Zhou, J Ferrucci, L Walston, J Guralnik, J Fried, L AF Cappola, A Xue, Q Zhou, J Ferrucci, L Walston, J Guralnik, J Fried, L TI Trajectories of IGF-1 and DHEAS and mortality SO GERONTOLOGIST LA English DT Meeting Abstract C1 Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Johns Hopkins Med Inst, Baltimore, MD 21205 USA. NIA, NIH, Longitudinal Studies Sect, Clin Res Branch, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2005 VL 45 SI 2 BP 7 EP 7 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 988QF UT WOS:000233615000012 ER PT J AU Williamson, J Miller, M Bryan, N Lazar, R Coker, L Launer, L AF Williamson, J Miller, M Bryan, N Lazar, R Coker, L Launer, L TI The action to control cardiovascular risk in diabetes: Memory in diabetes (ACCORD-MIND)-design and organization SO GERONTOLOGIST LA English DT Meeting Abstract C1 Ctr Cognit Res, Winston Salem, NC USA. Dept Publ Hlth Sci, Winston Salem, NC USA. Dept Radiol, Philadelphia, PA USA. Columbia Univ, Coll Phys & Surg, New York, NY USA. NIA, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2005 VL 45 SI 2 BP 12 EP 12 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 988QF UT WOS:000233615000025 ER PT J AU Kritchevsky, S Nicklas, B Newman, A AF Kritchevsky, S Nicklas, B Newman, A TI Body composition and metabolic and functional risk: New findings from the health, aging and body composition study SO GERONTOLOGIST LA English DT Meeting Abstract C1 Wake Forest Univ, Sch Med, Sticht Ctr Aging, Winston Salem, NC 27157 USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA 15213 USA. Wake Forest Univ Hlth Sci, Sticht Ctr Aging, Winston Salem, NC USA. NIA, Bethesda, MD 20892 USA. Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA. Univ Maryland, College Pk, MD 20742 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Vrije Univ Amsterdam, Amsterdam, Netherlands. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2005 VL 45 SI 2 BP 16 EP 18 PG 3 WC Gerontology SC Geriatrics & Gerontology GA 988QF UT WOS:000233615000036 ER PT J AU Revell, A Schaie, K AF Revell, A Schaie, K TI Measurement of APOE-E4 in relation to neuropsychological test performance over time SO GERONTOLOGIST LA English DT Meeting Abstract C1 NIMH, SSES, IRP, NIH,DHHS, Bethesda, MD 20892 USA. Penn State Univ, State Coll, PA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2005 VL 45 SI 2 BP 32 EP 32 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 988QF UT WOS:000233615000080 ER PT J AU Carnes, M Fielding, R Hodes, R Haak, L Whitelaw, N Kuchel, G AF Carnes, M Fielding, R Hodes, R Haak, L Whitelaw, N Kuchel, G TI Interdisciplinary research in aging: Moving from concept to reality SO GERONTOLOGIST LA English DT Meeting Abstract C1 Univ Wisconsin, Crr Womens Hlth Res, Madison, WI 53706 USA. Tufts Univ, Boston, MA 02111 USA. Natl Inst Aging, Washington, DC USA. Natl Acad Sci, Washington, DC 20418 USA. Natl Council Aging, Washington, DC 20024 USA. Univ Connecticut, Ctr Aging, Farmington, CT 06030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2005 VL 45 SI 2 BP 71 EP 71 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 988QF UT WOS:000233615000196 ER PT J AU Fried, L Guralnik, J AF Fried, L Guralnik, J TI Preclinical disability: Identifying high risk older adults and insights into precursors to health disparities SO GERONTOLOGIST LA English DT Meeting Abstract C1 NIA, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2005 VL 45 SI 2 BP 77 EP 78 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 988QF UT WOS:000233615000210 ER PT J AU Eisenstein, A Blackman, M AF Eisenstein, A Blackman, M TI Why seniors are turning to complementary and alternative medicine therapies SO GERONTOLOGIST LA English DT Meeting Abstract C1 Rush Univ, Med Ctr, Chicago, IL 60612 USA. NIH, NCCAM, Div Intramural Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2005 VL 45 SI 2 BP 115 EP 116 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 988QF UT WOS:000233615000306 ER PT J AU Manini, T Everhart, J Patel, K Schoeller, D Colbert, L Visser, M Tylavsky, F Bauer, D Goodpaster, B Harris, T AF Manini, T Everhart, J Patel, K Schoeller, D Colbert, L Visser, M Tylavsky, F Bauer, D Goodpaster, B Harris, T TI Physical activity, measured by doubly labeled water, and mortality among older adults: A preliminary report from the health aging and body composition study SO GERONTOLOGIST LA English DT Meeting Abstract C1 NIA, Bethesda, MD 20892 USA. NIDDK, Bethesda, MD USA. Univ Wisconsin, Madison, WI USA. Vrije Univ Amsterdam, NL-1081 HV Amsterdam, Netherlands. Univ Tennessee, Memphis, TN 38163 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Pittsburgh, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2005 VL 45 SI 2 BP 117 EP 118 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 988QF UT WOS:000233615000312 ER PT J AU Sehl, M Harris, T Newman, A Rubin, S Satterfield, S Kritchevsky, S Simonsick, E Tylavsky, F Cummings, S Garcia, M Cauley, J Nevitt, M AF Sehl, M Harris, T Newman, A Rubin, S Satterfield, S Kritchevsky, S Simonsick, E Tylavsky, F Cummings, S Garcia, M Cauley, J Nevitt, M TI Baseline predictors of rate-of-change in rapid 20 meter walk speed SO GERONTOLOGIST LA English DT Meeting Abstract C1 Univ Calif Los Angeles, Div Geriatr, Dept Med, Los Angeles, CA USA. NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA. Univ Calif San Francisco, Prevent Sci Grp, San Francisco, CA 94143 USA. Univ Tennessee, Coll Med, Dept Med, Memphis, TN 38163 USA. Wake Forest Univ Hlth Sci, Stitch Ctr Aging, Winston Salem, NC USA. NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA. Univ Tennessee, Coll Med, Dept Prevent Med, Memphis, TN 38163 USA. NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RI Cauley, Jane/N-4836-2015 OI Cauley, Jane/0000-0003-0752-4408 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 2005 VL 45 SI 2 BP 118 EP 119 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 988QF UT WOS:000233615000315 ER PT J AU Tennstedt, S Harris, S Link, C McKinlay, J Kusek, J AF Tennstedt, S Harris, S Link, C McKinlay, J Kusek, J TI Health care seeking for urinary incontinence in a diverse population SO GERONTOLOGIST LA English DT Meeting Abstract C1 New England Res Inst, Watertown, MA 02172 USA. NIDDKD, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2005 VL 45 SI 2 BP 120 EP 120 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 988QF UT WOS:000233615000319 ER PT J AU Newman, A Naydeck, B Boudreau, R Fried, L Fried, L Harris, T AF Newman, A Naydeck, B Boudreau, R Fried, L Fried, L Harris, T TI Multi-system physiologic integrity - Relationships to functional health in older adults SO GERONTOLOGIST LA English DT Meeting Abstract C1 Univ Pittsburgh, Pittsburgh, PA USA. Johns Hopkins Med Inst, Baltimore, MD 21205 USA. NIA, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2005 VL 45 SI 2 BP 124 EP 124 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 988QF UT WOS:000233615000330 ER PT J AU Guralnik, J Pahor, M Hadley, E AF Guralnik, J Pahor, M Hadley, E CA F LIFE Study Investigators TI A major trial of exercise to prevent disability: The LIFE study SO GERONTOLOGIST LA English DT Meeting Abstract C1 NIA, Bethesda, MD 20892 USA. Univ Florida, Gainesville, FL USA. EM jg48s@nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2005 VL 45 SI 2 BP 150 EP 151 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 988QF UT WOS:000233615000387 ER PT J AU Melzer, D Guralnik, J Wallace, R AF Melzer, D Guralnik, J Wallace, R TI Epidemiologic studies on disability prevention - Perspectives from the English longitudinal study of ageing (ELSA) and the US health and retirement study SO GERONTOLOGIST LA English DT Meeting Abstract C1 Peninsula Med Sch, Exeter EX2 5DW, Devon, England. NIA, Bethesda, MD 20892 USA. Univ Iowa, Iowa City, IA USA. EM david.melzer@pms.ac.uk NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2005 VL 45 SI 2 BP 153 EP 154 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 988QF UT WOS:000233615000393 ER PT J AU Bandinelli, S Ferrucci, L AF Bandinelli, S Ferrucci, L TI Molecules for gerontologists SO GERONTOLOGIST LA English DT Meeting Abstract C1 IOT Hosp, Dept Geriatr Rehabil, ASF, I-50125 Florence, Italy. NIA, Intramural Res Program, Baltimore, MD 21224 USA. EM stefania.bandinelli@asf.toscana.it NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2005 VL 45 SI 2 BP 191 EP 192 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 988QF UT WOS:000233615000493 ER PT J AU Yaffe, K Harris, T Rooks, R Van Eijk, J Kritchevsky, S Koster, A Penninx, B Bosma, H Kempen, G Newman, A Rubin, S Satterfield, S Atkinson, H Ayonayon, H Rosano, C AF Yaffe, K Harris, T Rooks, R Van Eijk, J Kritchevsky, S Koster, A Penninx, B Bosma, H Kempen, G Newman, A Rubin, S Satterfield, S Atkinson, H Ayonayon, H Rosano, C TI The role of biomedical factors in explaining socio-economic differences in cognitive decline SO GERONTOLOGIST LA English DT Meeting Abstract C1 NIA, Bethesda, MD 20892 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Kent State Univ, Kent, OH 44242 USA. Univ Maastricht, Dept Hlth Care Studies, Maastricht, Netherlands. Wake Forest Univ, Sch Med, Winston Salem, NC USA. VU Univ Med Ctr, Amsterdam, Netherlands. Univ Pittsburgh, Pittsburgh, PA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Tennessee, Coll Med, Memphis, TN USA. RI Bosma, Hans/A-6184-2013; Kempen, Gertrudis/H-5978-2016 OI Kempen, Gertrudis/0000-0002-7053-2198 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 2005 VL 45 SI 2 BP 202 EP 203 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 988QF UT WOS:000233615000518 ER PT J AU Atkinson, H Rosano, C Simonsick, E Williamson, J Davis, C Leng, X Rapp, S Cesari, M Newman, A Harris, T Rubin, S Yaffe, K Satterfield, S Kritchevsky, S AF Atkinson, H Rosano, C Simonsick, E Williamson, J Davis, C Leng, X Rapp, S Cesari, M Newman, A Harris, T Rubin, S Yaffe, K Satterfield, S Kritchevsky, S TI The modified mini-mental state examination (3MS) and gait speed decline SO GERONTOLOGIST LA English DT Meeting Abstract C1 Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. Univ Pittsburgh, Pittsburgh, PA USA. NIA, Bethesda, MD 20892 USA. Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. Univ Pittsburgh, Pittsburgh, PA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Tennessee, Ctr Hlth Sci, Coll Med, Memphis, TN 38163 USA. Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. RI Cesari, Matteo/A-4649-2008 OI Cesari, Matteo/0000-0002-0348-3664 NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2005 VL 45 SI 2 BP 248 EP 249 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 988QF UT WOS:000233615000646 ER PT J AU Faulkner, K Redfern, M Cauley, J Landsittel, D Studenski, S Zmuda, J Rosano, C Simonsick, E Harris, T Shorr, R Ayonayon, H Newman, A AF Faulkner, K Redfern, M Cauley, J Landsittel, D Studenski, S Zmuda, J Rosano, C Simonsick, E Harris, T Shorr, R Ayonayon, H Newman, A TI Multitasking: Reduced performance on concurrent reaction time and walking association with falls history in older adults SO GERONTOLOGIST LA English DT Meeting Abstract C1 Univ Pittsburgh, Pittsburgh, PA USA. Duquesne Univ, Pittsburgh, PA USA. Univ Pittsburgh, Pittsburgh, PA USA. NIA, Bethesda, MD 20892 USA. Univ Tennessee, Memphis, TN 38163 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. RI Cauley, Jane/N-4836-2015 OI Cauley, Jane/0000-0003-0752-4408 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 2005 VL 45 SI 2 BP 249 EP 249 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 988QF UT WOS:000233615000648 ER PT J AU Melzer, D Guralnik, J Pharoah, P AF Melzer, D Guralnik, J Pharoah, P TI Genetic variation and human aging: Large-scale associations study in the EPIC Cohort SO GERONTOLOGIST LA English DT Meeting Abstract C1 Peninsula Med Sch, Exeter, Devon, England. NIA, EDB Lab, Bethesda, MD 20892 USA. Univ Cambridge, Cambridge, England. NR 0 TC 0 Z9 0 U1 0 U2 1 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2005 VL 45 SI 2 BP 249 EP 249 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 988QF UT WOS:000233615000647 ER PT J AU Lauretani, F AF Lauretani, F TI Depicting therapeutic intervention for loss of mobility in older persons SO GERONTOLOGIST LA English DT Meeting Abstract C1 IOT Hosp, Tuscany Reg Hlth Agcy, Florence, Italy. Natl Inst Aging, Intramural Res Program, Baltimore, MD USA. Johns Hopkins Med Inst, Baltimore, MD 21205 USA. Tuscany Reg Hlth Agcy, Florence, Italy. Univ Parma, Sect Geriatr, I-43100 Parma, Italy. EM flauretani@inrca.it NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2005 VL 45 SI 2 BP 288 EP 290 PG 3 WC Gerontology SC Geriatrics & Gerontology GA 988QF UT WOS:000233615000753 ER PT J AU Landi, F Onder, G Cesari, M Russo, A Pahor, M Ferrucci, L Bernabei, R AF Landi, F Onder, G Cesari, M Russo, A Pahor, M Ferrucci, L Bernabei, R TI Pain and physical function among elderly subjects living in community - Results from the Ilsirente study SO GERONTOLOGIST LA English DT Meeting Abstract C1 Univ Sacred Heart, I-00168 Rome, Italy. Dept Aging & Geriatr Res, Inst Aging, Gainesville, FL USA. Natl Inst Aging, Longitudinal Studies Sect, Clin Res Branch, Baltimore, MD USA. RI Cesari, Matteo/A-4649-2008 OI Cesari, Matteo/0000-0002-0348-3664 NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2005 VL 45 SI 2 BP 294 EP 294 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 988QF UT WOS:000233615000766 ER PT J AU Penninx, B Bandinelli, S Lauretani, F Beekman, A Ferrucci, L AF Penninx, B Bandinelli, S Lauretani, F Beekman, A Ferrucci, L TI Late-life depression is associated with both hyper- and hypoactivity of the HPA-axis SO GERONTOLOGIST LA English DT Meeting Abstract C1 Vrije Univ Amsterdam, Med Ctr, NL-1081 HV Amsterdam, Netherlands. Natl Res Inst, Dept Geriatr, Florence, Italy. NIA, NIH, Longitudinal Studies Sect, Clin Res Branch, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2005 VL 45 SI 2 BP 299 EP 300 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 988QF UT WOS:000233615000781 ER PT J AU Simonsick, E Hicks, G Durso, S AF Simonsick, E Hicks, G Durso, S TI Translating research methods to the clinical environment SO GERONTOLOGIST LA English DT Meeting Abstract C1 Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA. NIA, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Bayview Med Ctr, Div Geriatr Med & Gerontol, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2005 VL 45 SI 2 BP 326 EP 327 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 988QF UT WOS:000233615000857 ER PT J AU Windham, B Kritchevsy, S Ferrucci, L AF Windham, B Kritchevsy, S Ferrucci, L TI More on 'easter eggs' in the Baltimore longitudinal study of aging SO GERONTOLOGIST LA English DT Meeting Abstract C1 NIA, Intramural Res Program, NIH, Baltimore, MD 21225 USA. Pepper Older Amer Indeppendence, Winston Salem, NC USA. NIA, NIH, Baltimore, MD 21224 USA. EM windhamgw@gre.nia.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2005 VL 45 SI 2 BP 384 EP 385 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 988QF UT WOS:000233615001107 ER PT J AU Kelley-Moore, J Lloyd, J Ayd-Simpson, L Kitner-Triolo, M Donohue, J Evans, M Zonderman, A AF Kelley-Moore, J Lloyd, J Ayd-Simpson, L Kitner-Triolo, M Donohue, J Evans, M Zonderman, A TI Why does "place" matter? Influence of social and physical environment on health over the life course SO GERONTOLOGIST LA English DT Meeting Abstract C1 Univ Maryland Baltimore Cty, Baltimore, MD 21228 USA. NIA, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2005 VL 45 SI 2 BP 405 EP 405 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 988QF UT WOS:000233615001166 ER PT J AU Harden, J Beverly, C Kane, R Mueller, C Teaster, P Beel-Bates, C Krichbaum, K AF Harden, J Beverly, C Kane, R Mueller, C Teaster, P Beel-Bates, C Krichbaum, K TI Nursing care of older adults formal interest group symposium honoring GSA president Dr. Terry Fulmer: Blueprint for better long term care through interdisciplinary collaboration SO GERONTOLOGIST LA English DT Meeting Abstract C1 Natl Inst Aging, NIH, Bethesda, MD 20892 USA. Univ Arkansas Med Sci, Ctr Aging, Little Rock, AR 72205 USA. Univ Minnesota, Sch Publ Hlth, Minneapolis, MN 55455 USA. Univ Minnesota, Sch Nursing, Minneapolis, MN 55455 USA. Univ Kentucky, Grad Ctr Gerontol, Lexington, KY 40536 USA. Univ Kentucky, Coll Publ Hlth, Dept Hlth Behav, Lexington, KY 40536 USA. Grand Valley State Univ, Kirkhof Coll Nursing, Grand Rapids, MI 49503 USA. EM Taylor_Harden@nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2005 VL 45 SI 2 BP 436 EP 437 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 988QF UT WOS:000233615001256 ER PT J AU Walston, J Semba, R Ferrucci, L AF Walston, J Semba, R Ferrucci, L TI Interdisciplinary approaches to the study of oxidative stress in human populations SO GERONTOLOGIST LA English DT Meeting Abstract C1 Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Johns Hopkins Med Inst, Baltimore, MD USA. Natl Inst Aging, Harbor Hosp, Longitudinal Studies Sect, Clin Res Branch NIH, Baltimore, MD 21225 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2005 VL 45 SI 2 BP 442 EP 444 PG 3 WC Gerontology SC Geriatrics & Gerontology GA 988QF UT WOS:000233615001272 ER PT J AU de Rekeneire, N Ferrucci, L Crepaldi, G AF de Rekeneire, N Ferrucci, L Crepaldi, G TI Glucose metabolism disorders and cardiovascular risk factors and disease SO GERONTOLOGIST LA English DT Meeting Abstract C1 Social & Sci Syst, Silver Spring, MD 20910 USA. Harbor Hosp, Clin Res Branch, Longitudinal Studies Sect, Natl Inst Aging,NIH, Baltimore, MD 21225 USA. CNR Ctr Aging, Padua, Italy. EM derekeneiren@yahoo.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2005 VL 45 SI 2 BP 444 EP 445 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 988QF UT WOS:000233615001273 ER PT J AU Schulz, R Stahl, S Burns, R Nichols, L AF Schulz, R Stahl, S Burns, R Nichols, L TI Reach II randomized clinical trial for Alzheimer's caregivers SO GERONTOLOGIST LA English DT Meeting Abstract C1 Univ Pittsburgh, Pittsburgh, PA 15260 USA. NIA, NIH, Bethesda, MD 20892 USA. Geriatr Grp Memphis, Memphis, TN USA. Univ Tennessee, VA Med Ctr, Memphis, TN 38104 USA. EM schulz@pitt.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2005 VL 45 SI 2 BP 489 EP 491 PG 3 WC Gerontology SC Geriatrics & Gerontology GA 988QF UT WOS:000233615001406 ER PT J AU Coppin, A Guralnik, J Shumway-Cook, A Ferrucci, L AF Coppin, A Guralnik, J Shumway-Cook, A Ferrucci, L TI Complex walking tasks: An innovative approach to assessing mobility disability SO GERONTOLOGIST LA English DT Meeting Abstract C1 NIA, Clin Res Branch, Harbor Hosp Ctr, Baltimore, MD 21225 USA. Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. NIA, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2005 VL 45 SI 2 BP 491 EP 492 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 988QF UT WOS:000233615001407 ER PT J AU Saczynski, J Jonsdottir, M Sigurdsson, S Eiriksdottir, G Jonsson, P Kjartansson, O van Buchem, M Gudnason, V Launer, L AF Saczynski, J Jonsdottir, M Sigurdsson, S Eiriksdottir, G Jonsson, P Kjartansson, O van Buchem, M Gudnason, V Launer, L TI Socio-demographic characteristics of phenotypes of cognitive reserve in a population sample: The ages study SO GERONTOLOGIST LA English DT Meeting Abstract C1 NIA, Bethesda, MD 20892 USA. Landspitali Univ Hosp Landakot, Reykjavik, Iceland. Iceland Heart Assoc, Reykjavik, Iceland. Landspitali Univ Hosp Hringbraut, Reykjavik, Iceland. Leiden Univ, Med Ctr, Leiden, Netherlands. RI Gudnason, Vilmundur/K-6885-2015 OI Gudnason, Vilmundur/0000-0001-5696-0084 NR 0 TC 0 Z9 0 U1 0 U2 1 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2005 VL 45 SI 2 BP 515 EP 515 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 988QF UT WOS:000233615001471 ER PT J AU Schooler, C Revell, A AF Schooler, C Revell, A TI Parental practices and willingness to ask for children's help later in life SO GERONTOLOGIST LA English DT Meeting Abstract C1 NIMH, SSES, IRP, NIH,DHHS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2005 VL 45 SI 2 BP 531 EP 531 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 988QF UT WOS:000233615001518 ER PT J AU Niederehe, G Evans, J AF Niederehe, G Evans, J TI NIMH update: Translating science into clinical applications in geriatric mental health SO GERONTOLOGIST LA English DT Meeting Abstract C1 NIMH, Geriatr Res Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2005 VL 45 SI 2 BP 597 EP 597 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 988QF UT WOS:000233615001684 ER PT J AU Levy, B Brommelhoff, J Merikengas, K AF Levy, B Brommelhoff, J Merikengas, K TI Reduced risk of anxiety in old age: Role of stigma SO GERONTOLOGIST LA English DT Meeting Abstract C1 Yale Univ, New Haven, CT USA. Natl Inst Drug & Alcohol Abuse, Bethesda, MD USA. Univ So Calif, Los Angeles, CA USA. NIMH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2005 VL 45 SI 2 BP 631 EP 632 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 988QF UT WOS:000233615001778 ER PT J AU Mehta, K Covinsky, K Newman, A Shorr, R Simonsick, E Ayonayon, H Rubin, S Yaffe, K AF Mehta, K Covinsky, K Newman, A Shorr, R Simonsick, E Ayonayon, H Rubin, S Yaffe, K TI Anxiety and depressive symptoms and decline in physical function over 5 years in the health, aging and body composition study SO GERONTOLOGIST LA English DT Meeting Abstract C1 Univ Calif San Francisco, Div Geriatr Med, San Francisco, CA 94143 USA. Univ Pittsburgh, Pittsburgh, PA USA. Univ Tennessee, Memphis, TN 38163 USA. NIA, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2005 VL 45 SI 2 BP 631 EP 631 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 988QF UT WOS:000233615001777 ER PT J AU Dik, M Ferrucci, L AF Dik, M Ferrucci, L TI Chronic inflammation and common geriatric syndromes: The longitudinal aging study Amsterdam SO GERONTOLOGIST LA English DT Meeting Abstract C1 Free Univ Amsterdam, Med Ctr, Inst Res Extramural Med EMGO, LASA,Fac Med, NL-1081 BT Amsterdam, Netherlands. NIA, NIH, Longitudinal Studies Sect, Clin Res Branch,Harbor Hosp, Baltimore, MD 21225 USA. EM mg.dik@vumc.nl; ferruccilu@grc.nia.nih.gov NR 0 TC 1 Z9 1 U1 1 U2 1 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2005 VL 45 SI 2 BP 654 EP 656 PG 3 WC Gerontology SC Geriatrics & Gerontology GA 988QF UT WOS:000233615001831 ER PT J AU Qin, LY Li, GR Qian, X Liu, YX Wu, XF Liu, B Hong, JS Block, ML AF Qin, LY Li, GR Qian, X Liu, YX Wu, XF Liu, B Hong, JS Block, ML TI Interactive role of the toll-like receptor 4 and reactive oxygen species in LPS-induced microglia activation SO GLIA LA English DT Article DE microglia; reactive oxygen species; TLR4; LPS; inflammation ID LIPOPOLYSACCHARIDE-BINDING PROTEIN; NF-KAPPA-B; DOPAMINERGIC-NEURONS; PARKINSONS-DISEASE; NADPH OXIDASE; INDUCED NEUROTOXICITY; TETRAZOLIUM SALT; GENE-EXPRESSION; HUMAN MONOCYTES; INFLAMMATION AB Microglia are activated by lipopolysaccharide (LPS) to produce neurotoxic pro-inflammatory factors and reactive oxygen species (ROS). While a multitude of LPS receptors and corresponding pathways have been identified, the detailed mechanisms mediating the microglial response to LPS are unclear. Using mice lacking a functional toll-like receptor 4 (TLR4), we demonstrate that TLR4 and ROS work in concert to mediate microglia activation, where the contribution from each pathway is dependent on the concentration of LPS. Immunocytochemical staining of microglia in neuronglia cultures with antibodies against F4/80 revealed that while TLR4(+/+) microglia were activated the low concentration of 1 ng/ml of LPS, TLR4(-/-) microglia exhibit activated morphology in response to LPS only at higher concentrations (100-1,000 ng/ml). Additionally, tumor necrosis factor-alpha (TNF-alpha) was only produced from higher concentrations (100-1,000 ng/ml) of LPS in TLR4(-/-) enriched microglia cultures. Diphenylene iodonium (DPI), an inhibitor of NADPH oxidase, reduced TNF-a production from TLR4(-/-) microglia. The influence of TLR4 on LPS-induced superoxide production was tested in rat enriched microglia cultures, where the presence or absence of serum failed to show any effect on the superoxide production. Further, both TLR4(-/-) and TLR4(+/+) microglia showed a similar increase in extracellular superoxide production when exposed to LPS (1-1,000 ng/ml). These data indicate that LPS-induced superoxide production in microglia is independent of TLR4 and that ROS derived from the production of extracellular superoxide in microglia mediates the LPS-induced TNF-a response of both the TLR4-dependent and independent pathway. (c) 2005 Wiley-Liss, Inc. C1 NIEHS, Inositol Phosphate Sect, Lab Signal Transduct, Res Triangle Pk, NC 27709 USA. NIEHS, Neuropharmacol Sect, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. Univ Florida, Coll Pharm, Dept Pharmacodynam, Gainesville, FL 32610 USA. RP Block, ML (reprint author), NIEHS, Inositol Phosphate Sect, Lab Signal Transduct, POB 12233,F1-01, Res Triangle Pk, NC 27709 USA. EM block@niehs.nih.gov RI liu, Bin/A-7695-2009 NR 45 TC 92 Z9 97 U1 1 U2 15 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0894-1491 J9 GLIA JI Glia PD OCT PY 2005 VL 52 IS 1 BP 78 EP 84 DI 10.1002/glia.20225 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 964GJ UT WOS:000231866800009 PM 15920727 ER PT J AU Feld, JJ Guindi, M Heathcote, EJ AF Feld, JJ Guindi, M Heathcote, EJ TI The lighter side of myeloma: an easily overlooked diagnosis SO GUT LA English DT Editorial Material C1 Univ Toronto, Dept Gastroenterol, Toronto, ON, Canada. Univ Toronto, Dept Pathol, Toronto, ON, Canada. RP Feld, JJ (reprint author), NIDDK, Liver Dis Sect, NIH, 10 Ctr Dr Rm 9B16,MSC 1800, Bethesda, MD 20892 USA. EM feldj@niddk.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 J9 GUT JI Gut PD OCT PY 2005 VL 54 IS 10 BP 1376 EP + DI 10.1136/gut.2004.057976 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 964JC UT WOS:000231876000009 PM 16162950 ER PT J AU Rzadzinska, AK Derr, A Kachar, B Noben-Trauth, K AF Rzadzinska, AK Derr, A Kachar, B Noben-Trauth, K TI Sustained cadherin 23 expression in young and adult cochlea of normal and hearing-impaired mice SO HEARING RESEARCH LA English DT Article DE age-related hearing loss; waltzer; cochlea; stereocilia; cadherin 23 ID MOUSE MODEL; INBRED STRAINS; FUNCTIONAL AGE; WALTZER MICE; STEREOCILIA; CDH23; MUTATIONS; CELLS; PRESBYCUSIS; PATHOLOGY AB Cadherin 23 encodes a single-pass transmembrane protein with 27 extracellular cadherin-domains and localizes to stereocilia where it functions as an inter-stereocilia link. Cadherin 23-deficient mice show congenital deafness in combination with circling behavior as a result of organizational defects in the stereocilia hair bundle, common inbred mouse strains carrying the hypornorphic Cdh23(753A) allele are highly susceptible to sensorineural hearing loss. Here, we show that an antibody (N1086) directed against the intracellular carboxyterminus reacts specifically with cadherin 23 and detects with high sensitivity the isoform devoid of the peptide encoded by exon 68 (CDH23 Delta 68). Cochlea, vestibule.. eye, brain and testis produce the CDH23 Delta 68 isoform in abundance and form moieties with different molecular weight due to variations in glycosylation content. In the cochlea, CDH23 Delta 68 expression is highest at postnatal day 1 (P1) and P7; expression is down regulated through P14 and P21 and persists at a low steady-state level throughout adulthood (P160). Furthermore, CDH23 Delta 68 expression levels in young and adult cochlea are similar among normal and hearing deficient strains (C3HeB/FeJ, C57BL/6J and BUB/BnJ). Finally, by immunofluorescence using an antibody (Pb240) specific for ecto-domain 14, we show that cadherin 23 localizes to stereocilia during hair bundle development in late gestation and early postnatal days. Cadherin 23-specific labeling becomes weaker as the hair bundle matures but faint labeling concentrated near the top of stereocilia is still detectable at P35. No labeling of cochlea stereocilia was observed with N1086. In conclusion, our data describe a cadherin 23-specific antibody with high affinity to the CDH23 Delta 68 isoform, reveal a dynamic cochlea expression and localization profile and show sustained cadherin 23 levels in adult cochlea of normal and hearing-impaired mice. (c) 2005 Elsevier B.V. All rights reserved. C1 Natl Inst Deafness & Other Commun Disorders, Sect Struct Cell Biol, Lab Cellular Biol, NIH, Rockville, MD 20855 USA. Natl Inst Deafness & Other Commun Disorders, Mol Biol Lab, Neurogenet Sect, Rockville, MD 20855 USA. RP Noben-Trauth, K (reprint author), Natl Inst Deafness & Other Commun Disorders, Sect Struct Cell Biol, Lab Cellular Biol, NIH, Rockville, MD 20855 USA. EM nobentk@nidcd.nih.gov FU Intramural NIH HHS NR 29 TC 28 Z9 29 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5955 J9 HEARING RES JI Hear. Res. PD OCT PY 2005 VL 208 IS 1-2 BP 114 EP 121 DI 10.1016/j.heares.2005.05.008 PG 8 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA 977TA UT WOS:000232824900011 PM 16005171 ER PT J AU Castro, O Gladwin, MT AF Castro, O Gladwin, MT TI Pulmonary hypertension in sickle cell disease: Mechanisms, diagnosis, and management SO HEMATOLOGY-ONCOLOGY CLINICS OF NORTH AMERICA LA English DT Article ID ACUTE CHEST SYNDROME; CONTINUOUS INTRAVENOUS EPOPROSTENOL; GENE-CLUSTER HAPLOTYPES; RISK-FACTORS; QUANTITATIVE ASSESSMENT; THALASSEMIA-INTERMEDIA; ARTERIAL-HYPERTENSION; DOPPLER ULTRASOUND; HEMOLYTIC-ANEMIA; IRON OVERLOAD AB In the last decade, pulmonary arterial hypertension (PAH) has emerged as one of the most frequent and serious complications in patients with sickle cell disease (SCD) [1-5]. The Sickle-Cell Pulmonary Hypertension Screening Study documented prospectively a 32% frequency of PAH in adult patients and its association with high mortality [4]. This and other prospective series (6,7] validated retrospective reports of the high frequency and Mortality of PAH in SCD [1,2]. It is not known why early reviews of die complications of SCD did not emphasize PAH, even though chromic lung disease and cor pulmonale were documented [8,9]. Although it is possible that the diagnosis was not recognized, it seems more likely that the high frequency of PAH in the current population of older SCD patients reflects the success in preventing the high mortality of severely affected children and young adults. The pathophysiology of PAH in SCD is unknown and probably multifactorial. All of the clinical manifestations of SCD ultimately derive from the tendency of deoxygenated HbS to polymerize and aggregate. Intracellular HbS polymerization increases the mechanic fragility of red blood cells, resulting in their premature mechanical destruction, that is, hemolytic anemia. In addition to mechanical stress on the erythrocyte membrane and cytoskeleton, inflammation and oxidant stress impair erythrocytic reductive potential and deplete ATP, contributing to energetic failure and increased surface phosphatidyl serine exposure [10], and marking die red cell for premature clearance. Polymerization also markedly reduces red blood cell deformability. That effect along with the increased tendency for sickle red blood cells to adhere to endothelium predisposes to episodes of vascular occlusion and ischemic damage to vital organs. All basic and clinical evidence obtained thus far indicates that intravascular hemolysis, which occurs in SCD [11,12], is an Important contributing factor to the development of PAH. Intravascular hemolysis interferes with the nitric oxide (NO) vasodilating system in two ways. It releases red blood cell arginase into the plasma, lowering the synthesis of NO [13]. At die same time, hemolysis increases the level of free plasma hemoglobin, which directly scavenges endodielial-derived NO [14,15]. This effect produces a state of endothelial dysfunction characterized by a resistance to NO, vasoconstriction, and secondary increases in the vasoconstrictor and mitogen endothelin 1. Hemolysis also activates the thrombotic system via direct effects on platelet activation through release of red cell ADP and indirectly by plasma hemoglobin-mediated NO scavenging and increased phosphatidyl serine exposure, which activate platelets and tissue factor [16]. The NO scavenging and prothrombotic effects of the damaged erythrocyte membrane, plasma red cell microvesicles, and plasma hemolysate likely produce progressive vascular pathologic remodeling, including intimal and smooth muscle proliferation and in situ thrombosis of the pulmonary arteries. PAH must be added to the classically recognized complications of hemolysis in SCD-anemia, cholelithiasis, and leg ulcers. It is unknown to what extent the endothelial dysfunction and NO resistance may contribute to the common vaso-occlusive manifestations of SCD (acute chest syndrome, painful events, priapism) and, in particular, to the proliferative cerebral vasculopathy that develops during childhood. This SCD vasculopathy bears similarities to PAH in its risk factors (low hemoglobin, high systolic blood pressure [17]) and pathologic features (large and medium sized vessel intimal and smooth muscle proliferation [18,19]). Nolan and colleagues showed in the journal, Blood June 28, 2005, Epub ahead of print), that markers of hemolysis (anemia, LDH, bilirubin, reticulocyte count) are significant risk factors for sickle cell-priapism. This provides additional support for the role of hemolysis and the NO system in SCD complications. In view of the mechanistic role of hemolysis in SCD-related pulmonary hypertension, it is not surprising that pulmonary hypertension also complicates thalassemia intermedia [20,21], hereditary spherocytosis [22], and other chronic hemolytic anemias [23-27]. The concept that the anemia, per se, is not involved in the genesis of PAH is supported by the absence of PAH reports in hypoproliferative nonhemolytic anemias such as iron deficiency, end-stage renal disease, and Fanconi anemia (Table 1). PAH is prevented in well-transfused patients with thalassemia major, in whom the anemia, ineffective erythropoiesis, and intramedullary hemolysis are largely suppressed [28]. C1 Howard Univ, Coll Med, Ctr Sickle Cell Dis, Washington, DC 20001 USA. NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. NHLBI, Vasc Therapeut Sect, Cardiovasc Branch, NIH, Bethesda, MD 20892 USA. RP Castro, O (reprint author), Howard Univ, Coll Med, Ctr Sickle Cell Dis, HURB-1,1840 7th St NW, Washington, DC 20001 USA. EM olcastro@aol.com NR 74 TC 49 Z9 51 U1 1 U2 7 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-8588 J9 HEMATOL ONCOL CLIN N JI Hematol. Oncol. Clin. North Am. PD OCT PY 2005 VL 19 IS 5 BP 881 EP + DI 10.1016/j.hoc.2005.07.007 PG 17 WC Oncology; Hematology SC Oncology; Hematology GA 981YK UT WOS:000233123700008 PM 16214649 ER PT J AU Terrault, NA Shiffman, ML Lok, AS Saab, S Gillespie, BW Seeff, LB AF Terrault, NA Shiffman, ML Lok, AS Saab, S Gillespie, BW Seeff, LB CA A2ALL Study Grp TI Transplant center experience explains differences in the risk of graft failure between hepatitis C virus (HCV)-infected recipients of living donor (LDLT) and deceased donor (DDLT) liver transplant recipients SO HEPATOLOGY LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 11-15, 2005 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. Virginia Commonwealth Univ, Richmond, VA USA. Univ Michigan, Study Grp A2ALL, Ann Arbor, MI USA. Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90024 USA. NIDDK, NIH, Bethesda, MD USA. NR 0 TC 1 Z9 1 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 2005 VL 42 IS 4 SU 1 BP 198A EP 199A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 972VC UT WOS:000232480300008 ER PT J AU Weiler-Normann, C Heller, T Sobao, Y Lutchman, G Borg, B Ghany, M Liang, TJ Hoofnagle, J AF Weiler-Normann, C Heller, T Sobao, Y Lutchman, G Borg, B Ghany, M Liang, TJ Hoofnagle, J TI Does treatment-induced recovery from hepatitis C result in the same immunological memory as spontaneous recovery? SO HEPATOLOGY LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 11-15, 2005 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 NIDDK, Liver Dis Branch, NIH, Bethesda, MD USA. NR 0 TC 1 Z9 1 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 2005 VL 42 IS 4 SU 1 BP 218A EP 218A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 972VC UT WOS:000232480300057 ER PT J AU Morishima, C Morgan, TR Gretch, DR Wright, EC Everhart, JE AF Morishima, C Morgan, TR Gretch, DR Wright, EC Everhart, JE TI Utility of TMA testing during antiviral treatment of advanced hepatitis C SO HEPATOLOGY LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 11-15, 2005 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 Univ Washington, Seattle, WA 98195 USA. Univ Calif Irvine, VA Med Ctr, Long Beach, CA USA. New England Res Inst, Watertown, MA 02172 USA. NIDDK, Bethesda, MD USA. NR 0 TC 2 Z9 2 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 2005 VL 42 IS 4 SU 1 BP 219A EP 219A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 972VC UT WOS:000232480300058 ER PT J AU DeRusso, PA Ye, W Haber, B Shneider, BL Sokol, RJ Whitington, PF Squires, RH Bezerra, J Shepherd, R Rosenthal, P Robuck, PR AF DeRusso, PA Ye, W Haber, B Shneider, BL Sokol, RJ Whitington, PF Squires, RH Bezerra, J Shepherd, R Rosenthal, P Robuck, PR TI Early growth failure following hepatoportoenterostomy is associated with liver transplantation or death in infants with biliary atresia SO HEPATOLOGY LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 11-15, 2005 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 Johns Hopkins Sch Med, Baltimore, MD USA. Univ Michigan, Ann Arbor, MI 48109 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Mt Sinai Med Ctr, New York, NY 10029 USA. Childrens Hosp, Denver, CO 80218 USA. Childrens Mem Hosp, Chicago, IL 60614 USA. Childrens Hosp Pittsburgh, Pittsburgh, PA 15213 USA. Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA. St Louis Childrens Hosp, St Louis, MO 63178 USA. Univ Calif San Francisco, Med Ctr, San Francisco, CA 94143 USA. NIDDK, NIH, Bethesda, MD 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 2005 VL 42 IS 4 SU 1 BP 222A EP 223A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 972VC UT WOS:000232480300067 ER PT J AU Loomba, R McBurney, R Park, Y Haynes-William, V Lutchman, GA Borg, BB Feld, JJ Rehermann, B Herrine, SK Alter, H Liang, JT Hoofnagle, JH Heller, T AF Loomba, R McBurney, R Park, Y Haynes-William, V Lutchman, GA Borg, BB Feld, JJ Rehermann, B Herrine, SK Alter, H Liang, JT Hoofnagle, JH Heller, T TI Acute hepatitis C: Clinical presentation, laboratory findings, and treatment outcomes. SO HEPATOLOGY LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 11-15, 2005 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 NIDDKD, NIH, Bethesda, MD 20892 USA. NIH, Ctr Clin, Bethesda, MD 20892 USA. Thomas Jefferson Univ, Jefferson Med Coll, Philadelphia, PA 19107 USA. NIH, Ctr Clin, Dept Transfus Med, Bethesda, MD 20892 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 2005 VL 42 IS 4 SU 1 BP 231A EP 231A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 972VC UT WOS:000232480300087 ER PT J AU Lok, AS Fung, SK Han, SH Chung, R Luketic, V Bzowej, N AF Lok, AS Fung, SK Han, SH Chung, R Luketic, V Bzowej, N CA NIH HBV OLT Study Grp TI Virological response and resistance to adefovir (ADV) therapy in liver transplant (OLT) patients SO HEPATOLOGY LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 11-15, 2005 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 Univ Calif Los Angeles, Los Angeles, CA 90024 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Miami, Coral Gables, FL 33124 USA. Virginia Commonwealth Univ, Med Coll Virginia, Richmond, VA 23298 USA. Calif Pacific Med Ctr, San Francisco, CA 94115 USA. NIH, NIH HBV OLT Study Grp, Ann Arbor, MI USA. NR 0 TC 6 Z9 6 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 2005 VL 42 IS 4 SU 1 BP 232A EP 232A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 972VC UT WOS:000232480300090 ER PT J AU Lee, JS AF Lee, JS TI Identification of novel prognostic subtype of hepatocellular carcinoma derived from hepatic progenitor cells by comparative functional genomic approach SO HEPATOLOGY LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 11-15, 2005 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 NCI, NIH, Bethesda, MD 20892 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 2005 VL 42 IS 4 SU 1 BP 238A EP 238A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 972VC UT WOS:000232480300103 ER PT J AU Reddy, R Gaglio, P Keeffe, E Soldevilla-Pico, C Emre, S Ishitani, M Fung, SK Lok, A AF Reddy, R Gaglio, P Keeffe, E Soldevilla-Pico, C Emre, S Ishitani, M Fung, SK Lok, A CA NIH HBV OLT Study Grp TI Characteristics and outcomes following liver transplantation (OLT) in patients with HBV-related hepatocellular carcinoma (HCC): Data from the us HBV-OLT study SO HEPATOLOGY LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 11-15, 2005 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 Univ Penn, Philadelphia, PA 19104 USA. Columbia Univ, Med Ctr, New York, NY 10027 USA. Stanford Univ, Palo Alto, CA 94304 USA. Univ Florida, Gainesville, FL 32611 USA. Mt Sinai Med Ctr, New York, NY 10029 USA. Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. Univ Michigan, Med Ctr, Ann Arbor, MI 48109 USA. NIH, NIH HBV OLT Study Grp, Ann Arbor, MI 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 2005 VL 42 IS 4 SU 1 BP 240A EP 240A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 972VC UT WOS:000232480300107 ER PT J AU Shin, EC Seifert, U Rice, C Feinstone, S Kloetzel, PM Rehermann, B AF Shin, EC Seifert, U Rice, C Feinstone, S Kloetzel, PM Rehermann, B TI Proteasomal antigen-processing is regulated by cytokines of the innate immune response in acute HCV infection SO HEPATOLOGY LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 11-15, 2005 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 NIDDK, Liver Dis Branch, NIH, Bethesda, MD USA. Humboldt Univ, Charite, Berlin, Germany. Rockefeller Univ, New York, NY 10021 USA. US FDA, Bethesda, MD 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 2005 VL 42 IS 4 SU 1 BP 245A EP 245A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 972VC UT WOS:000232480300121 ER PT J AU Sakai, Y Kaneko, S Nakamoto, Y Morrison, BJ Morris, JC AF Sakai, Y Kaneko, S Nakamoto, Y Morrison, BJ Morris, JC TI Successful prevention of primary tumor growth of metastatic liver cancer by genetically modified DC expressing interleukin-12 SO HEPATOLOGY LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 11-15, 2005 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 NCI, Metab Branch, NIH, Bethesda, MD 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 2005 VL 42 IS 4 SU 1 BP 273A EP 273A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 972VC UT WOS:000232480300191 ER PT J AU Fickert, P Wagner, M Marshall, HU Fuchsbichler, A Zollner, G Zatloukal, K Liu, J Waalkes, MP Cover, C Denk, H Hofmann, AF Jaeschke, H Trauner, M AF Fickert, P Wagner, M Marshall, HU Fuchsbichler, A Zollner, G Zatloukal, K Liu, J Waalkes, MP Cover, C Denk, H Hofmann, AF Jaeschke, H Trauner, M TI 24-norursodeoxycholic acid as novel therapeutic approach to sclerosing cholangitis in Mdr2 (ABCB4) knockout mice SO HEPATOLOGY LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 11-15, 2005 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 Lab Expt & Mol Hepatol, Graz, Austria. Karolinska Univ, Huddinge Hosp, Stockholm, Sweden. Dept Pathol, Graz, Austria. NIEHS, Lab Comparat Carcinogenesis, NCI, Res Triangle Pk, NC 27709 USA. Liver Res Inst, Tucson, AZ USA. Dept Med, San Diego, CA USA. NR 0 TC 1 Z9 1 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 2005 VL 42 IS 4 SU 1 BP 274A EP 274A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 972VC UT WOS:000232480300193 ER PT J AU Conjeevaram, HS Fried, MW Jeffers, LJ Terrault, N Wiley-Lucas, TE Afdhal, N Brown, RS Belle, SH Robuck, PR Howell, CD AF Conjeevaram, HS Fried, MW Jeffers, LJ Terrault, N Wiley-Lucas, TE Afdhal, N Brown, RS Belle, SH Robuck, PR Howell, CD TI Peginterferon alfa-2a and ribavirin in African American and Caucasian patients with chronic hepatitis C, genotype 1 SO HEPATOLOGY LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 11-15, 2005 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 Univ Michigan, Ann Arbor, MI 48109 USA. Univ N Carolina, Chapel Hill, NC USA. VA Med Ctr, Miami, FL USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Rush Univ, Med Ctr, Chicago, IL 60612 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. New York Presbyterian Columbia Presbyterian Ctr, New York, NY USA. Univ Pittsburgh, Pittsburgh, PA USA. NIDDK, NIH, Bethesda, MD USA. Univ Maryland, Baltimore, MD 21201 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2005 VL 42 IS 4 SU 1 BP 275A EP 276A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 972VC UT WOS:000232480300197 ER PT J AU Krawczynski, K Bartosch, B Meunier, JC Basham, L Culver, D Lavillette, D Kamili, S Cosset, FL Fattom, A AF Krawczynski, K Bartosch, B Meunier, JC Basham, L Culver, D Lavillette, D Kamili, S Cosset, FL Fattom, A TI Pathogenetic significance of neutralizing anti-HCV antibodies in acute and chronic hepatitis C virus (HCV) infection of chimpanzees treated with hyperimmune anti-HCV (Civacir (TM)) SO HEPATOLOGY LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 11-15, 2005 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 NCID, CCID, CDC, Div Viral Hepatitis, Atlanta, GA USA. Ecole Normale Super Lyon, F-69364 Lyon, France. NIAID, NIH, Bethesda, MD 20892 USA. Nabi Pharmaceut Inc, Rockville, MD USA. CDC, DVH, Atlanta, GA 30333 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2005 VL 42 IS 4 SU 1 BP 277A EP 277A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 972VC UT WOS:000232480300200 ER PT J AU Mix, H Weiler-Normann, C Lohse, A Rehermann, B AF Mix, H Weiler-Normann, C Lohse, A Rehermann, B TI Identification of T cell determinants in soluble liver antigen/liver-pancreas antigen,a major autoantigen in autoimmune hepatitis SO HEPATOLOGY LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 11-15, 2005 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 NIDDK, Liver Dis Branch, NIH, Bethesda, MD USA. Univ Mainz, D-6500 Mainz, Germany. Univ Hamburg, Hamburg, Germany. 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 2005 VL 42 IS 4 SU 1 BP 291A EP 292A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 972VC UT WOS:000232480300237 ER PT J AU Hasegawa, T Liu, J Wijeweera, J Malle, E Waalkes, MP Jaeschke, H AF Hasegawa, T Liu, J Wijeweera, J Malle, E Waalkes, MP Jaeschke, H TI Augmented hepatic ischemia-reperfusion injury despite reduced inflammation in steatotic livers of ob/ob mice SO HEPATOLOGY LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 11-15, 2005 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 Univ Arizona, Tucson, AZ USA. NCI, NIEHS, Res Triangle Pk, NC USA. Med Univ Graz, Graz, Austria. RI Malle, Ernst/D-3071-2013 NR 0 TC 1 Z9 1 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 2005 VL 42 IS 4 SU 1 BP 313A EP 314A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 972VC UT WOS:000232480300296 ER PT J AU Ruhl, CE Everhart, JE AF Ruhl, CE Everhart, JE TI Coffee drinking decreases the risk of chronic liver disease in the United States population SO HEPATOLOGY LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 11-15, 2005 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 Social & Sci Syst Inc, Silver Spring, MD USA. NIDDKD, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2005 VL 42 IS 4 SU 1 BP 348A EP 349A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 972VC UT WOS:000232480300382 ER PT J AU Welzel, TM McGlynn, KA Hsing, AW O'Brien, TR Pfeiffer, RM AF Welzel, TM McGlynn, KA Hsing, AW O'Brien, TR Pfeiffer, RM TI Impact of classification of Klatskin tumors on incidence of intra- and extrahepatic cholangiocarcinoma in the United States SO HEPATOLOGY LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 11-15, 2005 CL San Francisco, CA SP Amer Assoc Study Liver Dis C1 NCI, Rockville, MD 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 2005 VL 42 IS 4 SU 1 BP 384A EP 384A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 972VC UT WOS:000232480301020 ER EF