FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Chang, JD Sukhova, GK Libby, P Shvartz, E Lichtenstein, AH Hong, C Field, SJ Kennedy, C Madhavarapu, S Luo, J Wu, DQ Cantley, LC AF Chang, JD Sukhova, GK Libby, P Shvartz, E Lichtenstein, AH Hong, C Field, SJ Kennedy, C Madhavarapu, S Luo, J Wu, DQ Cantley, LC TI Deletion of the phoshoinositide 3-kinase (PI3K) p110gamma gene attenuates murine atherosclerosis 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 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Tufts Univ, Sch Med, Boston, MA 02111 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Connecticut, Farmington, CT 06032 USA. RI Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 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 909 BP U228 EP U229 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956401147 ER PT J AU Chu, JW Levine, RA Chua, S Ton-Nu, T Taub, C Sanz-Perez, T Morris, E Hua, LQ Hung, JW AF Chu, JW Levine, RA Chua, S Ton-Nu, T Taub, C Sanz-Perez, T Morris, E Hua, LQ Hung, JW TI Assessing mitral valve area in calcific mitral stenosis: A new solution by real-time three-dimensional echocardiography 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 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 1692 BP U396 EP U396 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956402274 ER PT J AU Cotter, G Kobrin, I Torre-Amione, G John, TR McMurray, JJ Frey, A Perchenet, L Hoover, P O'Connor, CM AF Cotter, G Kobrin, I Torre-Amione, G John, TR McMurray, JJ Frey, A Perchenet, L Hoover, P O'Connor, CM TI In-hospital worsening heart failure in patients with acute heart failure: Relation to renal failure, need for intotropes, CAD, hyponatremia and increased respiratory rate. A sub-group analysis from The VERITAS 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 Duke Univ, Ctr Med, Durham, NC USA. Actel Pharmaceut Ltd, Allschwil, Switzerland. Winters Ctr Heart Failure Res, Methodist DeBakey Heart Ctr, Houston, TX USA. San Francisco Vet Affairs Med Ctr, Cardiol Sect, San Francisco, CA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Glasgow, Dept Med & Therapeut, Glasgow G12 8QQ, Lanark, Scotland. Duke Univ, Ctr Med, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU S MA 2833 BP U661 EP U661 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956404137 ER PT J AU Cury, RC Nomura, CH Ferencik, M Hoffmann, U Fatima, U Teague, S Abbara, S Gold, HK Finn, A Jang, IK Brady, TJ Nieman, K AF Cury, RC Nomura, CH Ferencik, M Hoffmann, U Fatima, U Teague, S Abbara, S Gold, HK Finn, A Jang, IK Brady, TJ Nieman, K TI Comprehensive analysis of function and perfusion by 64-slice MDCT for detection of acute myocardial infarction 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 Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Nomura, Cesar/H-1636-2012 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 3186 BP U743 EP U744 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956404490 ER PT J AU Cury, RC Nieman, K Nomura, CH Ferencik, M Abbara, S Hoffmann, U Gold, HK Finn, A Jaffer, FA Jang, IK Brady, TJ AF Cury, RC Nieman, K Nomura, CH Ferencik, M Abbara, S Hoffmann, U Gold, HK Finn, A Jaffer, FA Jang, IK Brady, TJ TI Assessment of global and regional left ventricular function after acute myocardial infarction by 64-slice MDCT - Comparison with 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 Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Nomura, Cesar/H-1636-2012 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 2251 BP U527 EP U527 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956403173 ER PT J AU Daimon, M Gillinov, AM Liddicoat, J Saracino, G Fukuda, S Koyama, Y Hayase, M Ruel, M Ellis, SG Cohn, W Thomas, JD Shiota, T AF Daimon, M Gillinov, AM Liddicoat, J Saracino, G Fukuda, S Koyama, Y Hayase, M Ruel, M Ellis, SG Cohn, W Thomas, JD Shiota, T TI Dynamic changes in mitral annular area and motion during percutaneous transvenous mitral annuloplasty in ischemic mitral regurgitation: A real-time 3D echocardiographic 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 Cleveland Clin Fdn, Cleveland, OH 44195 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Ottawa, Inst Heart, Ottawa, ON, Canada. Texas Heart Inst, Houston, TX 77025 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 2947 BP U686 EP U686 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956404251 ER PT J AU Deguchi, JO Aikawa, E Libby, P Vachon, JR Inada, M Krane, SM Whittaker, P Aikawa, M AF Deguchi, JO Aikawa, E Libby, P Vachon, JR Inada, M Krane, SM Whittaker, P Aikawa, M TI MMP-13/collagenase-3 deletion promotes collagen accumulation and organization in mouse atherosclerotic plaques 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 Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. Univ Massachusetts, Sch Med, Worcester, MA 01605 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. RI Whittaker, Peter/F-1234-2011 OI Whittaker, Peter/0000-0002-5627-2166 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 1071 BP U263 EP U263 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956401309 ER PT J AU Dukkipati, S Schmidt, E Holmvang, G Gudhe, R Darrow, RD Slavin, G Fung, M Mallozi, R Dumoulin, CL Malchano, ZJ Kampa, G Dando, JD Christina, M Foo, TK Ruskin, JN Reddy, VY AF Dukkipati, S Schmidt, E Holmvang, G Gudhe, R Darrow, RD Slavin, G Fung, M Mallozi, R Dumoulin, CL Malchano, ZJ Kampa, G Dando, JD Christina, M Foo, TK Ruskin, JN Reddy, VY TI Electroanatomic substrate mapping of the left ventricle using real-time 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 Massachusetts Gen Hosp, Boston, MA 02114 USA. GE ASL East, Newton, MA USA. GE Global Rsch, Niskayuna, NY USA. GE ASL East, Hannover, 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 3039 BP U707 EP U707 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956404343 ER PT J AU Ebrahimi, R Shah, AP Wadhani, N Shingate, M Toggart, EJ Saleh, J AF Ebrahimi, R Shah, AP Wadhani, N Shingate, M Toggart, EJ Saleh, J TI Statin administration prior to percutaneous coronary interventions reduces adverse cardiovascular events - A meta-analysis 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 Los Angeles, Sch Med, W Los Angeles VA, Los Angeles, 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 2327 BP U544 EP U544 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956403248 ER PT J AU Ellinor, PT Sasse-Klaassen, S Probst, S Gerull, B Shin, JT Heuser, A Michely, B Yoerger, DM Krings, G Coplin, B Lange, PE Dec, GW Hennies, HC Thierfelder, L MacRae, CA AF Ellinor, PT Sasse-Klaassen, S Probst, S Gerull, B Shin, JT Heuser, A Michely, B Yoerger, DM Krings, G Coplin, B Lange, PE Dec, GW Hennies, HC Thierfelder, L MacRae, CA TI A novel locus for early-onset dilated cardiomyopathy, diffuse myocardial fibrosis and sudden death on chromosome 10q25-26 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 Massachusetts Gen Hosp, Boston, MA 02114 USA. Max Delbruck Ctr Mol Med, Berlin, Germany. Humboldt Univ, D-1086 Berlin, Germany. Albany Associates Cardiol, Albany, NY USA. German Heart Inst, Berlin, 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 2004 BP U471 EP U472 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956402586 ER PT J AU Erwin, PA Lin, AJ Golan, DE Michel, T AF Erwin, PA Lin, AJ Golan, DE Michel, T TI Differential S-nitrosylation of caveolae-targeted vs. cytosolic eNOS: Implications of subcellular targeting for signal protein S-nitrosylation 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 Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02114 USA. VA Boston Healthcare Syst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU S MA 883 BP U223 EP U223 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956401122 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 Gibson, CM Murphy, SA Pena, G Sanchez, PL Sanz, R Varela, JB Briales, JA Messa, L Fernandez, F Sanchis, J Moreu, J AF Gibson, CM Murphy, SA Pena, G Sanchez, PL Sanz, R Varela, JB Briales, JA Messa, L Fernandez, F Sanchis, J Moreu, J TI Pre-PCI TNK is associated with improved myocardial perfusion following PCI: Data from the GRACIA II 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 TIMI Study Grp, Boston, MA USA. ICICOR, Valladolid, Spain. Hosp Rio Hortega, Valladolid, Spain. Hosp Virgen Victoria, Malaga, Spain. Hosp Rio Carr, Palencia, Spain. Hosp Gen Leon, Leon, Spain. Hosp Clin Valencia, Valencia, Spain. Hosp Virgen Salud Toledo, Toledo, Spain. 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 2931 BP U682 EP U683 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956404235 ER PT J AU Gibson, CM Kirtane, AJ Aroesty, JM Murphy, SA Oman, H Takao, S Sabatine, MS Cannon, CP Braunwald, E AF Gibson, CM Kirtane, AJ Aroesty, JM Murphy, SA Oman, H Takao, S Sabatine, MS Cannon, CP Braunwald, E TI Clopidogrel is associated with improved angiographic measures in ST elevation myocardial infarction: A CLARITY-TIMI 28 substudy 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 TIMI Study Grp, Boston, MA USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02115 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 2695 BP U630 EP U630 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956403615 ER PT J AU Go, AS Udaltsova, N Fang, MC Chang, YC Jensvold, NG Henault, LE Singer, DE AF Go, AS Udaltsova, N Fang, MC Chang, YC Jensvold, NG Henault, LE Singer, DE TI Risk of thromboembolism and intracranial hemorrhage and effectiveness of warfarin by race/ethnicity in atrial fibrillation: The ATRIA 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 Kaiser Permanente No Calif, Oakland, CA USA. Univ Calif San Francisco, San Francisco, CA 94143 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 2214 BP U519 EP U519 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956403136 ER PT J AU Gregory, SA Ferencik, M Achenbach, S Yeh, RW Hoffmann, U Inglessis, I Cury, RC Nieman, K Laffan, JA Pomerantsev, EV Brady, TJ Semigran, MJ Jang, IK AF Gregory, SA Ferencik, M Achenbach, S Yeh, RW Hoffmann, U Inglessis, I Cury, RC Nieman, K Laffan, JA Pomerantsev, EV Brady, TJ Semigran, MJ Jang, IK TI Detection of transplant vasculopathy by contrast-enhanced 64-slice MDCT coronary angiography: Comparison to invasive coronary angiography and intravascular ultrasound 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 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Erlangen Nurnberg, Erlangen, 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 2588 BP U607 EP U607 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956403509 ER PT J AU He, ZH Arikawa, E Maeno, Y Scott, JA Bodyak, N Kang, PM King, GL AF He, ZH Arikawa, E Maeno, Y Scott, JA Bodyak, N Kang, PM King, GL TI Characterization of protein kinase C delta overexpression in cultured cardiomyocytes and cardiac function 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 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 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 1449 BP U341 EP U341 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956402032 ER PT J AU Heist, EK Taub, C Fan, D Alabiad, CR Arzola-Castaner, D Mela, T Mansour, M Reddy, VY Picard, MH Ruskin, JN Singh, JP AF Heist, EK Taub, C Fan, D Alabiad, CR Arzola-Castaner, D Mela, T Mansour, M Reddy, VY Picard, MH Ruskin, JN Singh, JP TI Left ventricular lead placement based on anatomy but not regional mechanical delay predicts the hemodynamic response to cardiac resynchronization therapy SO CIRCULATION LA English DT Meeting Abstract CT 78th Annual Scientific Session of the American-Heart-Association CY NOV 13-16, 2005 CL Dallas, TX SP Amer Heart Assoc C1 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 3365 BP U784 EP U784 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956405033 ER PT J AU Heller, EA Liu, E Yuan, Q Aikawa, ER Koehn, S Jones, K Freeman, M Moore, K Tager, A Luster, AD Gerszten, RE AF Heller, EA Liu, E Yuan, Q Aikawa, ER Koehn, S Jones, K Freeman, M Moore, K Tager, A Luster, AD Gerszten, RE TI The chemokine CXCL10 promotes atherogenesis by modulating the local balance of effector and regulatory T 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 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 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU 2 MA 913 BP U229 EP U229 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956401151 ER PT J AU Heller, EA Liu, E Tager, AM Sinha, S Roberts, JD Koehn, SL Libby, P Aikawa, ER Chen, JQ Huang, P Freeman, MW Moore, KJ Luster, AD Gerszten, RE AF Heller, EA Liu, E Tager, AM Sinha, S Roberts, JD Koehn, SL Libby, P Aikawa, ER Chen, JQ Huang, P Freeman, MW Moore, KJ Luster, AD Gerszten, RE TI Inhibition of atherogenesis in BLT1-deficient mice reveals a role for LTB4 and BLT1 in smooth muscle cell recruitment 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 New York Presbyterian, New York, NY USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU 2 MA 911 BP U229 EP U229 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956401149 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 Ho, PM Rumsfeld, JS Curtis, JP Eng, MH Havranek, EP Jones, PG Krumholz, HM Magid, DJ Messenger, JC Peterson, ED Rathore, SS Spertus, JA Masoudi, FA AF Ho, PM Rumsfeld, JS Curtis, JP Eng, MH Havranek, EP Jones, PG Krumholz, HM Magid, DJ Messenger, JC Peterson, ED Rathore, SS Spertus, JA Masoudi, FA TI Age and health status following non-ST elevation myocardial infarction 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 Denver VA Med Ctr, Denver, CO USA. Yale Univ, Sch Med, New Haven, CT USA. Univ Colorado, Hlth Sci Ctr, Denver, CO 80202 USA. Univ Denver, Hlth Med Ctr, Denver, CO 80202 USA. Mid Amer Heart Inst, Kansas City, KS USA. Yale Univ, Sch Med, New Haven, CT USA. Colorado Kaiser Permanente, Clin Res Unit, Denver, CO USA. Univ Colorado, Hlth Sci Ctr, Denver, CO 80202 USA. Duke Univ, Clin Res Inst, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU 2 MA 3739 BP U883 EP U883 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956406136 ER PT J AU Ho, PM Spertus, JA Masoudi, FA Reid, KJ Peterson, ED Krumholz, HM Rumsfeld, JS AF Ho, PM Spertus, JA Masoudi, FA Reid, KJ Peterson, ED Krumholz, HM Rumsfeld, JS TI Factors associated with discontinuing medications after acute myocardial infarction 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 Denver VA Med Ctr, Denver, CO USA. Mid Amer Heart Inst, Kansas City, KS USA. Denver Hlth Med Ctr, Denver, CO USA. Duke Univ, Clin Res Inst, Durham, NC USA. Yale Univ, Sch Med, New Haven, CT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU 2 BP U883 EP U883 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956406137 ER PT J AU Hoffmann, U Nagurney, TJ Pena, AJ Abbara, S Cury, R Moselewski, F Ferencik, M Brown, D Chae, C Siebert, U Gerszten, RE Jang, IK Brady, TJ AF Hoffmann, U Nagurney, TJ Pena, AJ Abbara, S Cury, R Moselewski, F Ferencik, M Brown, D Chae, C Siebert, U Gerszten, RE Jang, IK Brady, TJ TI MDCT in early triage of patients with acute chest pain - A prospective comparison to standard care 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 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 3189 BP U744 EP U744 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956404493 ER PT J AU Hoffmann, U Siebert, U Jadvar, H d'Othee, BJ AF Hoffmann, U Siebert, U Jadvar, H d'Othee, BJ TI A systematic review of the diagnostic accuracy of CT-based detection of significant coronary artery disease. A comparison of segment and patient-based approach 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 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ So Calif, Med Ctr, Keck Sch Med, Los Angeles, CA USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RI Janne d'Othee, Bertrand/E-8467-2010 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 3185 BP U743 EP U743 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956404489 ER PT J AU Hong, CC Tan, W Peterson, RT AF Hong, CC Tan, W Peterson, RT TI Chemical genetic analysis reveals the opposing effects of phosphatidylinositol-3 kinase and P44 MAP kinase signaling pathways on arterial specification 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 Massachusetts Gen Hosp, Charlestown, 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 408 BP U121 EP U121 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956400353 ER PT J AU Ichinose, F Buys, ES Lim, CC Janssens, S Liao, R Bloch, KD AF Ichinose, F Buys, ES Lim, CC Janssens, S Liao, R Bloch, KD TI Cardiac-specific overexpression of NO synthase 3 (NOS3) attenuates production of reactive oxygen species and preserves cardiac myocyte contractile function during endotoxemia 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 Massachusetts Gen Hosp, Boston, MA 02114 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Katholieke Univ Leuven, Louvain, Belgium. 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 1358 BP U324 EP U324 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956401596 ER PT J AU Izawa, A Ueno, T Ito, T Jurewicz, M Smith, RN Auchincloss, H Hynes, RO Sayegh, MH Abdi, R AF Izawa, A Ueno, T Ito, T Jurewicz, M Smith, RN Auchincloss, H Hynes, RO Sayegh, MH Abdi, R TI Role of donor-derived selectins in the development of acute and chronic cardiac allograft rejection 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 Harvard Univ, Sch Med, Childrens Hosp Boston, Transplantat Res Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Surg Transplantat Unit, Boston, MA 02115 USA. MIT, Canc Res Ctr, Howard Hughes Med Inst, Cambridge, MA 02139 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 1060 BP U260 EP U260 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956401298 ER PT J AU Jaffer, FA Nahrendorf, M Sosnovik, D Kelly, KA Aikawa, E Weissleder, R AF Jaffer, FA Nahrendorf, M Sosnovik, D Kelly, KA Aikawa, E Weissleder, R TI Multimodality MRI and near infrared fluorescence cellular imaging of inflammation in atherosclerosis 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 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 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 1187 BP U287 EP U287 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956401425 ER PT J AU Janardhanan, R Kenchaiah, S Pfeffer, MA McMurray, JJ Velazquez, EJ Califf, RM Weaver, WD White, H Park, Y Finn, PV Solomon, SD AF Janardhanan, R Kenchaiah, S Pfeffer, MA McMurray, JJ Velazquez, EJ Califf, RM Weaver, WD White, H Park, Y Finn, PV Solomon, SD TI Extent of coronary artery disease and cardiovascular outcomes in acute myocardial infarction complicated by heart failure, left ventricular dysfunction, or both: Findings from the VALsartan in acute myocardial iNfarcTion trial (VALIANT) 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. Western Infirm & Associated Hosp, Glasgow, Lanark, Scotland. Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. Henry Ford Heart & Vasc Inst, Detroit, MI USA. Auckland City Hosp, Auckland, New Zealand. Dana Farber Canc Inst, Boston, MA 02115 USA. RI Solomon, Scott/I-5789-2013 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 2431 BP U568 EP U568 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956403352 ER PT J AU Januzzi, J Sakhuja, R O'Donoghue, M Baggish, A Anwaruddin, S Chae, C Cameron, R Krauser, D Tung, R Camargo, C Lloyd-Jones, D AF Januzzi, J Sakhuja, R O'Donoghue, M Baggish, A Anwaruddin, S Chae, C Cameron, R Krauser, D Tung, R Camargo, C Lloyd-Jones, D TI Amino-terminal pro-brain natriuretic peptide strongly predicts one-year mortality in emergency department patients with dyspnea 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 Massachusetts Gen Hosp, Boston, MA 02114 USA. Northwestern Univ, Chicago, IL 60611 USA. RI Lloyd-Jones, Donald/C-5899-2009 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 3513 BP U817 EP U817 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956405181 ER PT J AU Jassal, DS Buys, E Neilan, TG Raher, MJ Ichinose, F Janssens, S Picard, MH Bloch, KD Scherrer-Crosbie, M AF Jassal, DS Buys, E Neilan, TG Raher, MJ Ichinose, F Janssens, S Picard, MH Bloch, KD Scherrer-Crosbie, M TI Cardiomyocyte-restricted nitric oxide synthase 3 overexpression attenuates left ventricular remodeling in mice with chronic pressure overload 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 Massachusetts Gen Hosp, Boston, MA 02114 USA. Katholieke Univ Leuven, Louvain, Belgium. 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 852 BP U217 EP U217 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956401091 ER PT J AU Jassal, DS Picard, MH Fifer, MA Palacios, IF Lowry, PA Vlahakes, GJ Neilan, TG Yoerger, DM AF Jassal, DS Picard, MH Fifer, MA Palacios, IF Lowry, PA Vlahakes, GJ Neilan, TG Yoerger, DM TI Sustained improvement in left ventricular diastolic function after alcohol septal ablation for hypertrophic obstructive 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 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 2401 BP U561 EP U561 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956403322 ER PT J AU Jessen, N Koh, HJ Arnolds, DE Lofgren, B Luptak, I Hirshman, MF Fujii, N Tian, R Goodyear, LJ AF Jessen, N Koh, HJ Arnolds, DE Lofgren, B Luptak, I Hirshman, MF Fujii, N Tian, R Goodyear, LJ TI Altered substrate metabolism and ablated AMPK alpha 2 activity in LKB1 knockout 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 Joslin Diabet Ctr, Boston, MA 02215 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RI Jessen, Niels/E-1731-2011 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 288 BP U89 EP U89 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956400234 ER PT J AU Jones, I Milan, DJ Ellinor, PT MacRae, C AF Jones, I Milan, DJ Ellinor, PT MacRae, C TI Zebrafish as a model system for drug mediated QT prolongation 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 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU S MA 4168 BP U64 EP U64 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956400114 ER PT J AU Kaye, DM Chien, KR Hoshijima, M Preovolos, A Mariani, J Bilney, A Hajjar, RJ Power, J AF Kaye, DM Chien, KR Hoshijima, M Preovolos, A Mariani, J Bilney, A Hajjar, RJ Power, J TI Recirculating delivery of a pseudophosphorylated mutant of phospholamban or the sarcoplasmic reticulum Ca2+ atpase prevents the progression of heart failure in a large animal model 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 Baker Med Res Inst, Melbourne, Vic, Australia. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Calif San Diego, Inst Mol Med, La Jolla, CA 92093 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 190 BP U68 EP U69 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956400136 ER PT J AU Kerwin, WS Ferguson, MS O'Brien, K Hatsukami, TS Yuan, C AF Kerwin, WS Ferguson, MS O'Brien, K Hatsukami, TS Yuan, C TI Why plaques enhance: A dynamic contrast-enhanced magnetic resonance imaging 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 Washington, Seattle, WA 98195 USA. Va Puget Sound Healthcare Syst, Seattle, WA 98195 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 2660 BP U622 EP U623 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956403580 ER PT J AU Kim, D Jaffer, FA Quinti, L Tung, CH Aikawa, E Libby, P Wessleder, R AF Kim, D Jaffer, FA Quinti, L Tung, CH Aikawa, E Libby, P Wessleder, R TI Imaging of cathepsin K activity in atherosclerosis using a protease-activatable near infrared fluorescence agent 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 Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 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 1069 BP U262 EP U262 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956401307 ER PT J AU Kirtane, AJ Sabatine, MS Aroesty, JM Murphy, SA Scirica, BM Pinto, DS Southard, M Stein, E Cannon, CP Braunwald, E Gibson, CM AF Kirtane, AJ Sabatine, MS Aroesty, JM Murphy, SA Scirica, BM Pinto, DS Southard, M Stein, E Cannon, CP Braunwald, E Gibson, CM TI Differences between streptokinase and fibrin-specific fibrinolytic therapy when co-administered with adjunctive clopidogrel: A CLARITY-TIMI 28 substudy 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 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. TIMI Study Grp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU S MA 2692 BP U629 EP U629 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956403612 ER PT J AU Kirtane, AJ Murphy, SA Aroesty, JM Sabatine, MS Cannon, CP Chang, A Takao, S Braunwald, E Gibson, CM AF Kirtane, AJ Murphy, SA Aroesty, JM Sabatine, MS Cannon, CP Chang, A Takao, S Braunwald, E Gibson, CM TI Angiographically-apparent thrombus following fibrinolytic therapy is associated with impaired myocardial perfusion in STEMI - A CLARITY-TIMI 28 substudy 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 Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. TIMI Study Grp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU S MA 2335 BP U546 EP U546 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956403256 ER PT J AU Kuwahara, E Otsuji, Y Zhu, F Ueno, T Yamamoto, H Yu, B Uemura, T Kubota, K Miyata, M Kisanuki, A Levine, RA Sakata, R AF Kuwahara, E Otsuji, Y Zhu, F Ueno, T Yamamoto, H Yu, B Uemura, T Kubota, K Miyata, M Kisanuki, A Levine, RA Sakata, R TI Mechanism of recurrent ischemic mitral regurgitation in the chronic phase following annuloplasty: Importance of augmented posterior mitral leaflet tethering 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, Kagoshima 890, Japan. 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 3326 BP U775 EP U775 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956404629 ER PT J AU Leopold, JA Handy, DE Stanton, RC Pitt, B Loscalzo, J AF Leopold, JA Handy, DE Stanton, RC Pitt, B Loscalzo, J TI Aldosterone decreases glucose-6-phosphate dehydrogenase expression in vascular endothelial cells by activating protein kinase A 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. Boston Univ, Med Ctr, Boston, MA 02215 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. Univ Michigan, Med Ctr, Ann Arbor, MI 48109 USA. Boston Univ, Med Ctr, Boston, 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 1573 BP U367 EP U367 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956402155 ER PT J AU Leopold, JA Handy, DE Stanton, RC Pitt, B Loscalzo, J AF Leopold, JA Handy, DE Stanton, RC Pitt, B Loscalzo, J TI Vascular gene transfer of glucose-6-phosphate dehydrogenase prevents aldosterone-mediated impaired vascular reactivity 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. Boston Univ, Med Ctr, Boston, MA USA. Joslin Diabet Ctr, Boston, MA 02215 USA. Univ Michigan, Med Ctr, Ann Arbor, MI 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 1333 BP U319 EP U319 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956401571 ER PT J AU Liu, E Sinha, S Force, T Dedhar, S Gerszten, R AF Liu, E Sinha, S Force, T Dedhar, S Gerszten, R TI Conditional deletion of ILK reveals an important role in T cell chemotaxis and Rac 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 Massachusetts Gen Hosp, Charlestown, MA USA. Tufts Univ New England Med Ctr, Boston, MA 02111 USA. British Columbia Canc Res Ctr, Vancouver, BC V5Z 1L3, Canada. 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 1594 BP U371 EP U371 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956402176 ER PT J AU Liu, XS Huang, YM Santos, J Swinnen, M Pellens, M Gillijns, H Leuven, U Scherrer-Crosbie, M Semigran, MJ Van de Werf, F Bloch, KD Janssens, S AF Liu, XS Huang, YM Santos, J Swinnen, M Pellens, M Gillijns, H Leuven, U Scherrer-Crosbie, M Semigran, MJ Van de Werf, F Bloch, KD Janssens, S TI Nitric oxide inhalation decreases myocardial injury in a porcine model of cardiac ischemia and reperfusion 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 Louvain, Louvain, Belgium. 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 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU 2 MA 375 BP U114 EP U114 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956400320 ER PT J AU Low, AF Tearney, GJ Bouma, BE Jang, IK AF Low, AF Tearney, GJ Bouma, BE Jang, IK TI Can intravascular ultrasound identify lipid-rich coronary plaques: Comparison with optical coherence tomography 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 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 2915 BP U679 EP U679 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956404219 ER PT J AU Luo, JC Wu, JP Shie, JL Rana, JS Laham, RJ Sellke, F Li, J AF Luo, JC Wu, JP Shie, JL Rana, JS Laham, RJ Sellke, F Li, J TI Enhanced IAP-2 expression is critical for the resistance of endothelial cells to TNF-alpha-induced apoptosis 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 Harvard Univ, Sch Med, BIDMC, Boston, MA USA. NR 0 TC 0 Z9 0 U1 3 U2 3 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 501 BP U141 EP U141 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956400446 ER PT J AU Ly, HQ Sabatine, MS Murphy, SA Kirtane, AJ Burns, J Aroesty, JM Cannon, CP Braunwald, E Gibson, CM AF Ly, HQ Sabatine, MS Murphy, SA Kirtane, AJ Burns, J Aroesty, JM Cannon, CP Braunwald, E Gibson, CM TI Clopidogrel abolishes the increased risk of reinfarction associated with higher platelet counts in patients with STEMI (Results from CLARITY-TIMI 28) 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. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. TIMI Study Grp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU S MA 1602 BP U375 EP U376 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956402184 ER PT J AU Mazumder, PK Buchanan, J Rasmussen, I Kahn, CR Accili, D Abel, ED AF Mazumder, PK Buchanan, J Rasmussen, I Kahn, CR Accili, D Abel, ED TI Paracrine regulation of cardiac metabolism by endothelial insulin signaling - Potential role of the nitric oxide/cyclic GMP pathway 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 Utah, Salt Lake City, UT 84112 USA. Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02115 USA. Columbia Univ, New York, NY 10027 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 372 BP U113 EP U113 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956400317 ER PT J AU Meadows, JL Milan, DJ AF Meadows, JL Milan, DJ TI Complete heart block as the primary presentation of thyrotoxicosis 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. 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 2969 BP U691 EP U691 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956404273 ER PT J AU Meadows, JL Milan, DJ AF Meadows, JL Milan, DJ TI Complete heart block as the primary presentation of thyrotoxicosis 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. 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 BP U45 EP U45 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956400049 ER PT J AU Mega, JL Murphy, S Cannon, CP AF Mega, JL Murphy, S Cannon, CP TI A meta-analysis of trials of intensive vs. moderate statin therapy for prevention of cerebrovascular events: Data from PROVE IT-TIMI 22, A to Z, and TNT 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 Massachusetts Gen Hosp, Boston, MA 02114 USA. TIMI Study Grp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU S MA 2859 BP U667 EP U667 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956404163 ER PT J AU Messas, E Pompidou, G Yosefy, C Guerrero, LJ Sullivan, S Witzke, C Menasche, P Carpentier, A Desnos, M Hagege, A Vlahakes, GJ Levine, RA AF Messas, E Pompidou, G Yosefy, C Guerrero, LJ Sullivan, S Witzke, C Menasche, P Carpentier, A Desnos, M Hagege, A Vlahakes, GJ Levine, RA TI Chordal cutting does not adversely affect LV contractile function 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 Med Paris 5, INSERM, U633, Hom Europeen Georges Pompidou,Dept Cardiol, Paris, France. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. Univ Med Paris 5, INSERM, Hop Europeen Georges Popmidou, Dept Cardiovasc Surg,U633, Paris, France. 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 2374 BP U555 EP U555 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956403295 ER PT J AU Nadkarni, S Pierce, M Park, H deBoer, J Houser, S Bressner, J Bouma, B Tearney, G AF Nadkarni, S Pierce, M Park, H deBoer, J Houser, S Bressner, J Bouma, B Tearney, G TI Polarization-sensitive optical coherence tomography for the analysis of collagen content in atherosclerotic plaques 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 Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 5 Z9 5 U1 0 U2 3 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 2913 BP U679 EP U679 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956404217 ER PT J AU Nagasaka, Y Mita, E Akashima, Y Ozaki, M Uezono, S AF Nagasaka, Y Mita, E Akashima, Y Ozaki, M Uezono, S TI In vivo transfection of cis-element decoy of early growth-response factor 1 attenuates monocrotaline-induced pulmonary hypertension and neointimal formation in young rats 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 Massachusetts Gen Hosp, Boston, MA 02114 USA. Tokyo Womens Med Univ, Dept Anesthesiol, Tokyo, Japan. Jikei Univ, Dept Anesthesiol, Tokyo, Japan. 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 888 BP U224 EP U224 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956401127 ER PT J AU Nahrendorf, M Jaffer, JA Kelly, K Sosnovik, D Reynolds, F Aikawa, E Libby, P Weissleder, R AF Nahrendorf, M Jaffer, JA Kelly, K Sosnovik, D Reynolds, F Aikawa, E Libby, P Weissleder, R TI Magneto-optical imaging of VCAM-1 expression using a linear affinity ligand derived from phage display 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 Massachusetts Gen Hosp, CMIR, Charlestown, MA USA. Brigham & Womens Hosp, Boston, MA 02115 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 1183 BP U286 EP U286 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956401421 ER PT J AU Neilan, TG Yoerger, DM Douglas, PS Marshall, JE Lawlor, D Picard, MH Wood, MJ AF Neilan, TG Yoerger, DM Douglas, PS Marshall, JE Lawlor, D Picard, MH Wood, MJ TI Persistent and reversible cardiac dysfunction among amateur marathon runners 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 Massachusetts Gen Hosp, Boston, MA 02114 USA. Duke Univ, Ctr Med, Durham, NC USA. Massachusetts Gen Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU S MA 3045 BP U709 EP U709 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956404349 ER PT J AU Neilan, TG Jassal, DS Buys, ES Raher, MJ Ichinose, F Perez-Sanz, TM Bayne, DB Graveline, A Janssens, S Picard, MH Scherrer-Crosbie, M Bloch, KD AF Neilan, TG Jassal, DS Buys, ES Raher, MJ Ichinose, F Perez-Sanz, TM Bayne, DB Graveline, A Janssens, S Picard, MH Scherrer-Crosbie, M Bloch, KD TI Endothelial nitric oxide synthase augments anthracycline-induced cardiac 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 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Louvain, B-3001 Louvain, Belgium. 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 486 BP U138 EP U138 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956400431 ER PT J AU Neilan, TG Perez-Sanz, TM Jassal, DS Raher, MJ Buys, ES Bayne, DB Derumeaux, G Bloch, KD Picard, MH Scherrer-Crosbie, M AF Neilan, TG Perez-Sanz, TM Jassal, DS Raher, MJ Buys, ES Bayne, DB Derumeaux, G Bloch, KD Picard, MH Scherrer-Crosbie, M TI Tissue Doppler imaging predicts left ventricular dysfunction in a murine model of anthracycline-induced cardiac 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 Massachusetts Gen Hosp, Boston, MA 02114 USA. INSERM, E0226, Lyon, France. 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 2782 BP U650 EP U650 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956404086 ER PT J AU Neilan, TG Ton-Nu, TT Levine, RA Kawase, Y Yoneyama, R Hoshino, K McGregor, J Hayase, M del Monte, F Hajjar, RJ Picard, MH Hung, J AF Neilan, TG Ton-Nu, TT Levine, RA Kawase, Y Yoneyama, R Hoshino, K McGregor, J Hayase, M del Monte, F Hajjar, RJ Picard, MH Hung, J TI Reduction in tissue Doppler-derived indices of myocardial function occurs prior to any deterioration in left ventricular ejection fraction in chronic mitral regurgitation 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 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 2564 BP U601 EP U601 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956403485 ER PT J AU Newton-Cheh, C Guo, CY Larson, MG Benjamin, EJ Kathiresan, S O'Donnell, CJ Levy, D Hirschhorn, JN Vasan, R AF Newton-Cheh, C Guo, CY Larson, MG Benjamin, EJ Kathiresan, S O'Donnell, CJ Levy, D Hirschhorn, JN Vasan, R TI Clinical and genetic correlates of blood aldosterone to renin ratio 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 Massachusetts Gen Hosp, Boston, MA 02114 USA. Framingham Heart Dis Epidemiol Study, Framingham, MA USA. Boston Univ, Sch Med, Boston, MA 02215 USA. Childrens Hosp, Boston, MA 02115 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 2441 BP U570 EP U570 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956403362 ER PT J AU Nieman, K Cury, RC Nomura, CH Ferencik, M Abbara, S Hoffmann, U Gold, HK Finn, A Jaffer, F Jang, IK Brady, TJ AF Nieman, K Cury, RC Nomura, CH Ferencik, M Abbara, S Hoffmann, U Gold, HK Finn, A Jaffer, F Jang, IK Brady, TJ TI Contrast-enhanced 64-slice MDCT of acute myocardial infarction - A segmental comparison with 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 Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Nomura, Cesar/H-1636-2012 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 2253 BP U527 EP U527 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956403175 ER PT J AU Novikov, M Grazette, L Aoyama, T Matsui, T Rosenzweig, A AF Novikov, M Grazette, L Aoyama, T Matsui, T Rosenzweig, A TI Cardiac gene transfer of activated serum and glucocorticoid-responsive kinase-1 (SGK1) reduces injury after ischemia-reperfusion 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 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 785 BP U202 EP U202 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956401024 ER PT J AU Nu, TTT Levine, RA Perez-Sanz, TM Scherrer-Crosbie, M AF Nu, TTT Levine, RA Perez-Sanz, TM Scherrer-Crosbie, M TI Transition from mitral valve prolapse to incomplete mitral leaflet closure: Central role of papillary muscle position 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 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 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 1691 BP U396 EP U396 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956402273 ER PT J AU Nu, TTT Pradhan, AD Morris, EL Birmingham, MJ Picard, MH AF Nu, TTT Pradhan, AD Morris, EL Birmingham, MJ Picard, MH TI Patent foramen ovalis diagnostic rate varies with harmonic frequencies 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 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU S MA 2772 BP U647 EP U647 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956404076 ER PT J AU Okuhira, KI Fitzgerald, ML Freeman, MW AF Okuhira, KI Fitzgerald, ML Freeman, MW TI Proteomic and functional analysis of the abcal efflux complex reveals the importance of a 1 beta-syntrophin interaction 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 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU S MA 585 BP U158 EP U158 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956400530 ER PT J AU Ota, H Kaneki, M Iijima, K Kozaki, K Akishita, M Ouchi, Y AF Ota, H Kaneki, M Iijima, K Kozaki, K Akishita, M Ouchi, Y TI Inhibition of Sirt1, a human homolog of yeast longevity gene, Sir2, induces senescence-like phenotype in human 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 Univ Tokyo, Tokyo, Japan. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA USA. Kyorin Univ, Dept Geriatr Med, Tokyo, Japan. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU S MA 1498 BP U351 EP U351 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956402081 ER PT J AU Pande, AN Kohler, RH Aikawa, E Wiessleder, R Jaffer, FA AF Pande, AN Kohler, RH Aikawa, E Wiessleder, R Jaffer, FA TI Detection of macrophage activity in atherosclerosis in vivo using multi-channel, high-resolution laser scanning fluorescent microscopy 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. Massachusetts Gen Hosp, Ctr Mol Imaging Rsch, Charlestown, 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 1182 BP U286 EP U286 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956401420 ER PT J AU Pape, LA Januzzi, J Cooper, JV Fattori, R Evangelista, A Suzuki, T Trimarchi, S Bossone, E Hutchison, S Beckman, J Nienaber, C Isselbacher, E Eagle, KA AF Pape, LA Januzzi, J Cooper, JV Fattori, R Evangelista, A Suzuki, T Trimarchi, S Bossone, E Hutchison, S Beckman, J Nienaber, C Isselbacher, E Eagle, KA CA IRAD Investigators TI Many type A aortic dissections occur at diameters less than generally perceived 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 Massachusetts, Sch Med, Worcester, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Michigan Hlth Syst, Ann Arbor, MI USA. Univ Bologna, S Orsola M Malpighi Hosp, Bologna, Italy. Univ Barcelona, Hosp Gen Valle Hebron, Barcelona, Spain. Univ Tokyo, Tokyo, Japan. Inst Policlin San Donato, San Donato Milanese, Italy. CNR, Lecce, Italy. Mayo Clin, Rochester, MN USA. St Michaels Hosp, Toronto, ON M5B 1W8, Canada. Brigham & Womens Hosp, Boston, MA 02115 USA. Univ Rostock, Rostock, 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 2544 BP U596 EP U596 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956403465 ER PT J AU Paramsothy, P Retzlaff, BM Knopp, RH Fish, B Kahn, SE Ostlund, RE AF Paramsothy, P Retzlaff, BM Knopp, RH Fish, B Kahn, SE Ostlund, RE TI Diminished cholesterol absorption and heightened synthesis in obesity and insulin resistance: Evidence from plasma sterol levels 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 Washington, Div Cardiol, Seattle, WA 98195 USA. Univ Washington, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. Univ Washington, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98195 USA. Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. Washington Univ, St Louis, MO 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 1083 BP U265 EP U265 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956401321 ER PT J AU Patel, AM Kim, JB Roberts, A Aragam, J AF Patel, AM Kim, JB Roberts, A Aragam, J TI Dyspnea on exertion in a 59 year old man with pectus excavatum and a heart murmur 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 Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Partners Ctr Genet & Genom, Boston, MA USA. VA Boston Healthcare Syst, W Roxbury, 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 2965 BP U690 EP U690 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956404269 ER PT J AU Patel, AM Kim, JB Roberts, A Aragam, J AF Patel, AM Kim, JB Roberts, A Aragam, J TI Dyspnea on exertion in a 59-year-old man with pectus excavatum and a heart murmur 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. Harvard Univ, Partners Ctr Genet & Genom, Boston, MA 02115 USA. VA Boston Healthcare Syst, W Roxbury, 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 BP U44 EP U44 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956400045 ER PT J AU Persson, H Lonn, E Edner, M Baruch, L Lang, CC Morton, JJ Ostergren, J McKelvie, RS AF Persson, H Lonn, E Edner, M Baruch, L Lang, CC Morton, JJ Ostergren, J McKelvie, RS TI Diastolic dysfunction in heart failure with preserved systolic - Function need for objective evidence. Results from the CHARM echocardiographic substudy - CHARMES 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 Danderyd Hosp, Stockholm, Sweden. Populat Hlth Res Inst, Hamilton, ON, Canada. Bronx Vet Affairs Med Ctr, Bronx, NY USA. Univ Dundee, Ninewells Hosp & Med Sch, Dundee DD1 9SY, Scotland. Univ Glasgow, Western Infirm, Glasgow G11 6NT, Lanark, Scotland. Karolinska Univ Hosp, Stockholm, Sweden. 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 1991 BP U469 EP U469 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956402573 ER PT J AU Pinto, DS Kirtane, AJ Sabatine, MS Murphy, SA Aroesty, JM Southard, M Perez-Estabrooks, L Cannon, CP Braunwald, E Gibson, M AF Pinto, DS Kirtane, AJ Sabatine, MS Murphy, SA Aroesty, JM Southard, M Perez-Estabrooks, L Cannon, CP Braunwald, E Gibson, M CA CLARITY-TIMI 28 Investigators TI Relationship of blood glucose with adverse outcomes among patients with ST-segment elevation myocardial infarction in the CLARITY-TIMI-28 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 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. TIMI Study Grp, Boston, MA USA. Perfuse Angiog Core Lab, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU S MA 3150 BP U758 EP U758 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956404553 ER PT J AU Plomondon, ME Magid, DJ Masoudi, FA Jones, PG Barry, LC Havranek, E Peterson, ED Krumholz, HM Spertus, JA Rumsfeld, JS AF Plomondon, ME Magid, DJ Masoudi, FA Jones, PG Barry, LC Havranek, E Peterson, ED Krumholz, HM Spertus, JA Rumsfeld, JS TI The impact of angina on patient satisfaction after acute myocardial infarction 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 Denver VA Med Ctr, Denver, CO USA. Colorado Permanente Med Grp, Aurora, CO USA. Denver Hlth Med Ctr, Denver, CO USA. UMKC, Mid Amer Heart Inst, Kansas City, MO USA. Yale Univ, Med Ctr, New Haven, CT USA. Duke Univ, Med Ctr, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU S MA 3813 BP U899 EP U899 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956406210 ER PT J AU Potente, M Urbich, C Sasaki, K Hofmann, WK Heeschen, C Aicher, A Kollipara, R DePinho, RA Dimmeler, S AF Potente, M Urbich, C Sasaki, K Hofmann, WK Heeschen, C Aicher, A Kollipara, R DePinho, RA Dimmeler, S TI The forkhead transcription factors Fox01 and Fox03a are important modulators of postnatal vessel formation and maturation 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 Charite, Dept Hematol & Oncol, Berlin, Germany. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 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 297 BP U90 EP U90 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956400243 ER PT J AU Qureshi, A Shahzad, K Hung, J Arzola-Castaner, D Chung, JH Ruskin, JN Handschumacher, MD Singh, JP Picard, MH AF Qureshi, A Shahzad, K Hung, J Arzola-Castaner, D Chung, JH Ruskin, JN Handschumacher, MD Singh, JP Picard, MH TI Dyssynchrony score - A new method of quantifying cardiac dyssynchrony by three-dimensional echocardiography 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 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 1970 BP U464 EP U464 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956402552 ER PT J AU Raghupathy, A Nienaber, C Myrmel, T Fattori, R Sechtem, U Oh, J Cooper, JV Eagle, K Isselbacher, E Bossone, E AF Raghupathy, A Nienaber, C Myrmel, T Fattori, R Sechtem, U Oh, J Cooper, JV Eagle, K Isselbacher, E Bossone, E CA IRAD Investigators TI Geographical variation in acute type a aortic dissection: Insights from the International Registry of Aortic Dissection (IRAD) 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 Michigan, Ann Arbor, MI 48109 USA. Univ Rostock, D-2500 Rostock, Germany. Univ Tromso Hosp, N-9012 Tromso, Norway. Univ Bologna, Hosp S Orsola, Bologna, Italy. Robert Bosch Krankenhaus, Stuttgart, Germany. Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. CNR, Lecce, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU S MA 3330 BP U776 EP U776 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956404633 ER PT J AU Raher, MJ Thibault, H Liu, R Hataishi, R Denumeaux, G Bloch, KD Ichinose, F Picard, MH Scherrer-Crosbie, M AF Raher, MJ Thibault, H Liu, R Hataishi, R Denumeaux, G Bloch, KD Ichinose, F Picard, MH Scherrer-Crosbie, M TI Impaired coronary artery reserve in nitric oxide synthase 3 deficient mice: A myocardial contrast echocardiography 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 Massachusetts Gen Hosp, Boston, MA 02114 USA. INSERM, E0226, F-69008 Lyon, France. 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 3131 BP U731 EP U731 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956404435 ER PT J AU Ray, KK Cannon, CP Morrow, DA Cairns, R McCabe, CH Ridker, PM Braunwald, E AF Ray, KK Cannon, CP Morrow, DA Cairns, R McCabe, CH Ridker, PM Braunwald, E TI CRP is additive and independent of Apo B/A1 ratio in explaining the clinical benefits of atorvastatin 80mg in ACS patients in PROVE IT-TIMI 22 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 TIMI Study Grp, Boston, MA USA. Nottingham Clin Res Grp, Nottingham, England. Brigham & Womens Hosp, Boston, MA 02115 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 2324 BP U543 EP U544 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956403245 ER PT J AU Reddy, VY Neuzil, P Pitschner, HF Kuniss, M Kralovec, S Kanova, M Laragy, M Mihalik, TA Taborsky, M Ruskin, JN AF Reddy, VY Neuzil, P Pitschner, HF Kuniss, M Kralovec, S Kanova, M Laragy, M Mihalik, TA Taborsky, M Ruskin, JN TI Clinical experience with a balloon cryoablation catheter for pulmonary vein isolation in patients with atrial fibrillation: One-year results 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 Massachusetts Gen Hosp, Boston, MA 02114 USA. Homolka Hosp, Prague, Czech Republic. Max Planck Inst Physiol & Clin Res, Kerckhoff Klin, D-6350 Bad Nauheim, Germany. Cryocath Technol Inc, Montreal, PQ, Canada. 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 2630 BP U616 EP U616 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956403550 ER PT J AU Reddy, VY Neuzil, P Themistoclakis, S Bonso, A Rossillo, A Raviele, A Saliba, W Schwelkert, R Melsky, J Olsen, M Ruskin, JN Natale, A AF Reddy, VY Neuzil, P Themistoclakis, S Bonso, A Rossillo, A Raviele, A Saliba, W Schwelkert, R Melsky, J Olsen, M Ruskin, JN Natale, A TI Initial clinical experience with a balloon laser ablation catheter for pulmonary vein isolation in patients with atrial fibrillation 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 Massachusetts Gen Hosp, Boston, MA 02114 USA. Homolka Hosp, Prague, Czech Republic. Umberto Hosp, Venice, Italy. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Cardiofocus Inc, Norton, 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 2358 BP U551 EP U552 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956403279 ER PT J AU Sabatine, MS Cannon, CP Morrow, DA Montalescot, G Dellborg, M Pons, JL Keltai, M Murphy, SA McCabe, CH Gibson, CM Antman, EM Braunwald, E AF Sabatine, MS Cannon, CP Morrow, DA Montalescot, G Dellborg, M Pons, JL Keltai, M Murphy, SA McCabe, CH Gibson, CM Antman, EM Braunwald, E TI Low-molecular-weight heparin is associated with superior outcomes compared with unfractionated heparin in patients with ST-elevation myocardial infarction: A CLARITY-TIMI 28 substudy 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. Hop La Pitie Salpetriere, Inst Cardiol, Paris, France. Sahlgrens Univ Hosp, S-41345 Gothenburg, Sweden. Ctr Med Potosi, San Luis Potosi, Mexico. Semmelweis Univ, Hungarian Inst Cardiol, H-1085 Budapest, Hungary. TIMI Study Grp, Boston, MA USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU 2 MA 2694 BP U630 EP U630 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956403614 ER PT J AU Sakata, S Lebeche, D Sakata, N Sakata, Y Chemaly, ER Liang, LF Padmanabhan, P Takaki, M del Monte, F Hajjar, RJ AF Sakata, S Lebeche, D Sakata, N Sakata, Y Chemaly, ER Liang, LF Padmanabhan, P Takaki, M del Monte, F Hajjar, RJ TI Adenoviral gene transfer of calcium-handling proteins restores mechanical and energetic left-ventricular function in aorta-banded rats 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 Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA USA. Nara Med Univ, Dept Physiol 2, Kashihara, Nara 634, Japan. 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 148 BP U59 EP U59 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956400094 ER PT J AU Schulze, PC Liu, HL Choe, E Yoshioka, J Shalev, A Bloch, KD Lee, RT AF Schulze, PC Liu, HL Choe, E Yoshioka, J Shalev, A Bloch, KD Lee, RT TI Transcriptional regulation of thioredoxin-interacting protein by nitric oxide enhances thioredoxin activity 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, Cambridge, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Wisconsin, Dept Med, Madison, WI 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 1104 BP U270 EP U270 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956401342 ER PT J AU Sebastian, R Schodel, J Huang, PL Kuhlencordt, PJ AF Sebastian, R Schodel, J Huang, PL Kuhlencordt, PJ TI Ezetimibe reduces arteriosclerosis in apolipoprotein E knockout mice despite endothelial nitric oxide synthase deficiency 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 Wuerzburg, Wurzburg, Germany. 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 238 BP U78 EP U78 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956400184 ER PT J AU Shah, AP Ebrahimi, R Wadhani, N Toggart, EJ Rubin, SA AF Shah, AP Ebrahimi, R Wadhani, N Toggart, EJ Rubin, SA TI Beta-blocker therapy in acute myocardial infarction: A meta-analysis of clinical trials 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 Los Angeles, Sch Med, Los Angeles, CA 90024 USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 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 2096 BP U493 EP U493 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956403018 ER PT J AU Shah, J Pinto, DS Kirtane, AJ Bhandiwad, A Murphy, SA Scirica, B Stein, E Nguyen, M Morrow, D Sabatine, MS de Lemos, J Gibson, M AF Shah, J Pinto, DS Kirtane, AJ Bhandiwad, A Murphy, SA Scirica, B Stein, E Nguyen, M Morrow, D Sabatine, MS de Lemos, J Gibson, M TI Electrocardiographic localization of the infarct-related artery in inferior myocardial infarction 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 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Emory Univ, Atlanta, GA 30322 USA. TIMI Study Grp, Boston, MA USA. Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. Univ Texas, SW Med Ctr, Dallas, TX 75230 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 2333 BP U546 EP U546 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956403254 ER PT J AU Shaw, SY Westly, EC Clemons, PA Schreiber, SL AF Shaw, SY Westly, EC Clemons, PA Schreiber, SL TI Novel human endothelial cell phenotypes based on response to systematic chemical perturbation 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 Massachusetts Gen Hosp, Broad Inst, Boston, MA 02114 USA. Howard Hughes Med Inst, Broad Inst, Cambridge, 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 2432 BP U568 EP U569 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956403353 ER PT J AU Shie, JL Luo, JC Laham, RJ Sellke, F Li, J AF Shie, JL Luo, JC Laham, RJ Sellke, F Li, J TI RTEF-1, a novel transcriptional stimulator, regulates FGF receptor I expression in hypoxic 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 Harvard Univ, Sch Med, BIDMC, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU S MA 300 BP U91 EP U91 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956400246 ER PT J AU Singh, BN Geffen, D Hohnloser, SH AF Singh, BN Geffen, D Hohnloser, SH TI Dronedarone is safe and effective in maintaining sinus rhythm in atrial fibrillation in patients with pre-specified recurrence risk factors 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 VA Greater Los Angeles Healthcare Syst W Los Ange, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. Univ Frankfurt Klinikum, Med Klin 4, D-6000 Frankfurt, 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 2366 BP U553 EP U553 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956403287 ER PT J AU Sips, PY Buys, ES Rogge, E Dewerchin, M Brouckaert, P AF Sips, PY Buys, ES Rogge, E Dewerchin, M Brouckaert, P TI Functional knockout of the soluble guanylate cyclase alpha 1 subunit leads to gender-specific hypertension while retaining sensitivity to nitric oxide 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 State Univ Ghent VIB, B-9000 Ghent, Belgium. Massachusetts Gen Hosp, Charlestown, MA USA. Catholic Univ Louvain VIB, B-3000 Louvain, Belgium. 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 25 PY 2005 VL 112 IS 17 SU S MA 747 BP U191 EP U192 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956400692 ER PT J AU Soccio, T Zhang, YY Bacci, S Mlynarski, W Raggio, G Menzaghi, C Nolan, D Duffy, J Di Paola, R Trischitta, V Doria, A AF Soccio, T Zhang, YY Bacci, S Mlynarski, W Raggio, G Menzaghi, C Nolan, D Duffy, J Di Paola, R Trischitta, V Doria, A TI Haplotype-tagging polymorphisms at the adiponectin receptor 1 (ADIPORI) locus are associated with lower ADIPOR1 expression and increased cardiovascular risk in type 2 diabetes 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 Joslin Diabet Ctr, Boston, MA USA. Ist Sci Casa Sollievo Sofferenza, San Giovanni Rotondo, Italy. RI Di Paola, Rosa/G-7813-2011; Trischitta, Vincenzo/K-1487-2016 OI Di Paola, Rosa/0000-0001-5837-9111; Trischitta, Vincenzo/0000-0003-1174-127X 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 3642 BP U849 EP U849 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956406039 ER PT J AU Sonel, AF Zahid, M Fine, MJ Good, CB AF Sonel, AF Zahid, M Fine, MJ Good, CB TI Do physicians assess risk of adverse outcomes differently in black vs. white patients?: A comparison of an objective risk score and physician assessed risk in non-ST-elevation acute coronary syndromes 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 VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Rsch & Promot, Pittsburgh, PA 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 3700 BP U862 EP U863 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956406097 ER PT J AU Song, YQ Manson, JE Meigs, JB Ridker, PM Buring, JE Liu, S AF Song, YQ Manson, JE Meigs, JB Ridker, PM Buring, JE Liu, S TI Adiposity as compared with the metabolic syndrome in predicting future risk of cardiovascular events among 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 Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. Brigham & Womens Hosp, Div Cardiovasc Dis, Donald Reynolds Cntr Cardiovasc Rsch, Boston, MA 02115 USA. Cntr Cardiovasc Dis Prevent, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Ambultory Care & Prevent, Boston, MA 02115 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 3662 BP U854 EP U854 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956406059 ER PT J AU Sosnovik, DE Nahrendorf, M Grazette, L Reynolds, F Rosenzweig, A Weissleder, R Josephson, L AF Sosnovik, DE Nahrendorf, M Grazette, L Reynolds, F Rosenzweig, A Weissleder, R Josephson, L TI Molecular imaging of low levels of cardiomyocyte apoptosis with a targeted magneto-fluorescent contrast agent 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 Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 3 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 3037 BP U706 EP U707 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956404341 ER PT J AU Teerlink, JR Bergman, MR Li, LY Zhu, BQ Karliner, JS Lovett, DH AF Teerlink, JR Bergman, MR Li, LY Zhu, BQ Karliner, JS Lovett, DH TI Chronic cardiac MMP-2 transgene expression independently induces marked ventricular remodeling and systolic 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 San Francisco VA Med Ctr, San Francisco, CA USA. RI Teerlink, John/D-2986-2012 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 564 BP U154 EP U154 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956400509 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 Thibault, H Gomez, L Chalabreysse, L Ciobanu-Jurcut, R AF Thibault, H Gomez, L Chalabreysse, L Ciobanu-Jurcut, R TI Strain rate accurately identifies infarcted myocardium in 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 Fac Med Lyon, Lyon, France. 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 2562 BP U600 EP U601 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956403483 ER PT J AU Trimarchi, S Nienaber, CA Rampoldi, V Myrmel, T Suzuki, T Tolva, V Deeb, MG Upchurch, G Cooper, JV Fang, JM Isselbacher, EM Sundt, T Eagle, KA AF Trimarchi, S Nienaber, CA Rampoldi, V Myrmel, T Suzuki, T Tolva, V Deeb, MG Upchurch, G Cooper, JV Fang, JM Isselbacher, EM Sundt, T Eagle, KA TI Role and results of surgery in acute type B aortic dissection - Insights from the International Registry of Aortic Dissection (IRAD) 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 Policlin San Donato, San Donato Milanese, Italy. Univ Rostock, D-2500 Rostock, Germany. Univ Tromso Hosp, N-9012 Tromso, Norway. Univ Tokyo, Tokyo, Japan. Univ Michigan, Coordinating Ctr IRAD, Ann Arbor, MI 48109 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU S MA 3329 BP U776 EP U776 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956404632 ER PT J AU Tsai, TT Fattori, R Trimarchi, S Nienaber, C Myrmel, T Hutchison, S Krankenhaus, RB Cooper, JV Fang, JM Pape, L Januzzi, J Eagle, KA Isselbacher, E AF Tsai, TT Fattori, R Trimarchi, S Nienaber, C Myrmel, T Hutchison, S Krankenhaus, RB Cooper, JV Fang, JM Pape, L Januzzi, J Eagle, KA Isselbacher, E CA IRAD Investigators TI Long-term survival in patients with Type B acute aortic dissection: Insights from the international registry of aortic dissection (IRAD) 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 Michigan, Ann Arbor, MI 48109 USA. Univ Bologna, S Orsola M Malpighi Hosp, Bologna, Italy. Inst Policlin San Donato, San Donato Milanese, Italy. Univ Rostock, Rostock, Germany. Univ Tromso Hosp, N-9012 Tromso, Norway. St Michaels Hosp, Toronto, ON M5B 1W8, Canada. Robert Bosch Krankenhaus, Stuttgart, Germany. Univ Massachusetts Hosp, Worcester, MA 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 2547 BP U597 EP U597 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956403468 ER PT J AU Tsai, TT Evangelista, A Nienaber, C Sechtem, U Krankenhaus, RB Fattori, R Myrmel, T Llovet, A Cooper, JV Fang, JM Isselbacher, E Eagle, KA AF Tsai, TT Evangelista, A Nienaber, C Sechtem, U Krankenhaus, RB Fattori, R Myrmel, T Llovet, A Cooper, JV Fang, JM Isselbacher, E Eagle, KA CA IRAD Investigators TI Long-term survival in patients presenting with type A acute aortic dissection: Insights from the international registry of aortic dissection (IRAD) 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 Michigan, Ann Arbor, MI 48109 USA. Univ Barcelona, Hosp Gen Valle Hebron, Barcelona, Spain. Univ Rostock, Rostock, Germany. Robert Bosch Krankenhaus, Stuttgart, Germany. Univ Bologna, S Orsola M Malpighi Hosp, Bologna, Italy. Univ Tromso Hosp, N-9012 Tromso, Norway. Univ Madrid, Hosp 12 Octubre, Madrid 3, Spain. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU S MA 2545 BP U596 EP U597 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956403466 ER PT J AU Udelson, JE McGrew, F Flores, E Ibrahim, H Koshkarian, G Katz, S O'Brien, T Johnson, RH Zimmer, C Orlandi, C Konstam, MA AF Udelson, JE McGrew, F Flores, E Ibrahim, H Koshkarian, G Katz, S O'Brien, T Johnson, RH Zimmer, C Orlandi, C Konstam, MA TI Effects of the vasopressin V2 receptor antagonist, tolvaptan, on the long-term progression of left ventricular dilatation in patients with 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 Tufts New England Med Ctr, Boston, MA USA. Stern Cardiovasc Ctr, Memphis, TN USA. Georgia Heart Specialists, Covington, GA USA. N Ohio Res, Sandusky, OH USA. Desert Cardiol Tucson, Tucson, AZ USA. Yale Univ, New Haven, CT 06520 USA. Ralph H Johnson VAMC, Charleston, SC USA. Otsuka Maryland Res Inst, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU S MA 2415 BP U564 EP U564 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956403336 ER PT J AU van Kimmenade, RR Januzzi, JL Lainchbury, JG Bayes-Genis, A Santalo, M Ordonez, J Richards, MA Pinto, YM AF van Kimmenade, RR Januzzi, JL Lainchbury, JG Bayes-Genis, A Santalo, M Ordonez, J Richards, MA Pinto, YM TI Combining NT-PROBNP and GFR to predict prognosis in patients with heart failure: An analysis from the international collaborative of NT-proBNP (ICON) 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 Hosp Maastricht, Maastricht, Netherlands. Massachusetts Gen Hosp, Boston, MA 02114 USA. Christchurch Sch Med & Hlth Sci, Christchurch, New Zealand. Hosp Santa Creu & Sant Pau, Barcelona, Spain. RI Ordonez-Llanos, Jorge/A-9335-2010; Ordonez-Llanos, Jordi/B-4961-2011; Bayes-Genis, Antoni/C-4002-2015; Kimmenade, R.R.J./L-4432-2015 OI Ordonez-Llanos, Jordi/0000-0003-4896-5832; Bayes-Genis, Antoni/0000-0002-3044-197X; 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 3519 BP U819 EP U819 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956405187 ER PT J AU van Kimmenade, RR Januzzi, JL Bakker, JA Sharma, UC Crijns, HJ Menheere, PP Pinto, YM AF van Kimmenade, RR Januzzi, JL Bakker, JA Sharma, UC Crijns, HJ Menheere, PP Pinto, YM TI Galectin-3 predicts 60 days mortality in heart failure: A step towards multimarker strategy in heart failure. Results from the ProBNP investigation of dyspnea in the emergency department (PRIDE) 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 Hosp Maastricht, Maastricht, Netherlands. Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Kimmenade, R.R.J./L-4432-2015 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 3141 BP U733 EP U733 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956404445 ER PT J AU Vermeersch, P Buys, ES Glenn, M Pokreisz, P Pellens, M Gillijns, H Dewerchin, M Brouckaert, P Bloch, KD Janssens, S AF Vermeersch, P Buys, ES Glenn, M Pokreisz, P Pellens, M Gillijns, H Dewerchin, M Brouckaert, P Bloch, KD Janssens, S TI Gender-specific modulation of baseline vascular function and the response to arterial injury by soluble guanylate cyclase 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 Catholic Univ Louvain VIB, B-3000 Louvain, Belgium. Massachusetts Gen Hosp, Charlestown, MA USA. State Univ Ghent VIB, B-9000 Ghent, Belgium. RI Vermeersch, Pieter/M-8352-2016 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 1507 BP U353 EP U353 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956402089 ER PT J AU Vermeersch, P Pokreisz, P Marsboom, G Buys, ES Gillijns, H Pellens, M Swinnen, M Ichinose, F Dewerchin, M Brouckaert, P Bloch, KD Janssens, S AF Vermeersch, P Pokreisz, P Marsboom, G Buys, ES Gillijns, H Pellens, M Swinnen, M Ichinose, F Dewerchin, M Brouckaert, P Bloch, KD Janssens, S TI Soluble guanylate cyclase deficiency selectively abolishes NO-mediated pulmonary vasodilation and increases the pulmonary vascular remodeling response to chronic hypoxia 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 Catholic Univ Louvain VIB, B-3000 Louvain, Belgium. Massachusetts Gen Hosp, Charlestown, MA USA. State Univ Ghent VIB, B-9000 Ghent, Belgium. RI Vermeersch, Pieter/M-8352-2016 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 U31 EP U32 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956400017 ER PT J AU Vermeersch, P Pokreisz, P Marsboom, G Buys, ES Gillijns, H Pellens, M Swinnen, M Ichinose, F Dewerchin, M Brouckaert, P Bloch, KD Janssens, S AF Vermeersch, P Pokreisz, P Marsboom, G Buys, ES Gillijns, H Pellens, M Swinnen, M Ichinose, F Dewerchin, M Brouckaert, P Bloch, KD Janssens, S TI Soluble guanylate cyclase deficiency selectively abolishes NO-mediated pulmonary vasodilation and increases the pulmonary vascular remodeling response to chronic hypoxia 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 Catholic Univ Louvain VIB, B-3000 Louvain, Belgium. Massachusetts Gen Hosp, Charlestown, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Vermeersch, Pieter/M-8352-2016 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 1146 BP U278 EP U278 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956401384 ER PT J AU Wu, GF Rana, J Wykrzykowska, JJ Kang, PM Li, J Gibson, CM Sellke, FW Laham, RJ AF Wu, GF Rana, J Wykrzykowska, JJ Kang, PM Li, J Gibson, CM Sellke, FW Laham, RJ TI Exercise-induced expression of anglogenic cytokines in normal and infarcted 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 Sun Yat Sen Univ, Affiliated Hosp 1, Guangzhou, Peoples R China. Harvard Univ, Sch Med, BIDMC, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 25 PY 2005 VL 112 IS 17 SU S MA 1241 BP U300 EP U300 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956401479 ER PT J AU Wu, SM Fujiwara, Y Orkin, SH AF Wu, SM Fujiwara, Y Orkin, SH TI Identification of a committed myocardial progenitor cell from the developing embryo 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 Childrens Hosp, Boston, MA 02115 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 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 344 BP U107 EP U108 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 979PD UT WOS:000232956400289 ER PT J AU Blouin, AM Thannickal, TC Worley, PF Baraban, JM Reti, IM Siegel, JM AF Blouin, AM Thannickal, TC Worley, PF Baraban, JM Reti, IM Siegel, JM TI Narp immunostaining of human hypocretin (orexin) neurons - Loss in narcolepsy SO NEUROLOGY LA English DT Article; Proceedings Paper CT 34th Annual Meeting of the Society-for-Neuroscience CY OCT 23-27, 2004 CL San Diego, CA SP Soc Neurosci ID EXPRESSION AB Objective: To investigate whether neuronal activity-regulated pentraxin (Narp) colocalizes with hypocretin ( Hcrt or orexin) in the normal human brain and to determine if Narp staining is lost in the narcoleptic human brain. Background: Human narcolepsy is characterized by a loss of the peptide hypocretin in the hypothalamus. This loss could result from the degeneration of neurons containing hypocretin or from a more specific loss of the ability of these neurons to synthesize Hcrt. Narp has been found to colocalize with hypocretin in the rat hypothalamus. Methods: We investigated the distribution of Narp in three normal and four narcoleptic human postmortem brains using immunohistochemistry with an antibody to Narp. Colocalization studies of Narp and hypocretin were also performed in two normal brains using immunohistochemistry with an antibody to Narp and an antibody to hypocretin. Results: We found that Narp colocalizes with hypocretin in the lateral hypothalamic area (LHA), the dorsomedial hypothalamus (DMH), the dorsal hypothalamic area (DHA), and the posterior hypothalamic area (PHA) of the normal human. The number of Narp-positive neurons was reduced by 89% in these areas of the narcoleptic hypothalamus. In contrast, Narp staining in the paraventricular (Pa) and supraoptic nuclei (SO) of the human hypothalamus did not differ between normal and narcoleptic brains. Conclusions: This finding supports the hypothesis that narcolepsy results from the specific loss of hypocretin neurons. Loss of hypothalamic Narp may contribute to the symptoms of narcolepsy. C1 VA Greater Los Angeles Healthcare Sys, North Hills, CA 91343 USA. Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA USA. Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD USA. RP Siegel, JM (reprint author), VA Greater Los Angeles Healthcare Sys, 16111 Plummer St,Neurobiol Res 151A3, North Hills, CA 91343 USA. EM jsiegel@ucla.edu OI Baraban, Jay/0000-0002-8165-2638 FU NHLBI NIH HHS [HL41370]; NIMH NIH HHS [MH64109]; NINDS NIH HHS [NS14610] NR 9 TC 74 Z9 76 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD OCT 25 PY 2005 VL 65 IS 8 BP 1189 EP 1192 DI 10.1212/01.wnl.0000175219.01544.c8 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 977OR UT WOS:000232813600011 PM 16135770 ER PT J AU Subramanian, A Tamayo, P Mootha, VK Mukherjee, S Ebert, BL Gillette, MA Paulovich, A Pomeroy, SL Golub, TR Lander, ES Mesirov, JP AF Subramanian, A Tamayo, P Mootha, VK Mukherjee, S Ebert, BL Gillette, MA Paulovich, A Pomeroy, SL Golub, TR Lander, ES Mesirov, JP TI Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE microarray ID FALSE DISCOVERY RATE; X-INACTIVATION; LUNG; ADENOCARCINOMA; DISTINCT; RNA; PROGRESSION; CHROMOSOME; MICROARRAY; MECHANISM AB Although genomewide RNA expression analysis has become a routine tool in biomedical research, extracting biological insight from such information remains a major challenge. Here, we describe a powerful analytical method called Gene Set Enrichment Analysis (GSEA) for interpreting gene expression data. The method derives its power by focusing on gene sets, that is, groups of genes that share common biological function, chromosomal location, or regulation. We demonstrate how GSEA yields insights into several cancer-related data sets, including leukemia and lung cancer. Notably, where single-gene analysis finds little similarity between two independent studies of patient survival in lung cancer, GSEA reveals many biological pathways in common. The GSEA method is embodied in a freely available software package, together with an initial database of 1,325 biologically defined gene sets. C1 MIT, Broad Inst, Cambridge, MA 02141 USA. Harvard Univ, Cambridge, MA 02141 USA. Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02446 USA. Duke Univ, Inst Genome Sci & Policy, Ctr Interdisciplinary Engn Med & Appl Sci, Durham, NC 27708 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Pulm & Crit Care Med, Boston, MA 02114 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. Harvard Univ, Sch Med, Childrens Hosp, Dept Neurol, Boston, MA 02115 USA. MIT, Dept Biol, Cambridge, MA 02142 USA. MIT, Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. RP Lander, ES (reprint author), MIT, Broad Inst, 320 Charles St, Cambridge, MA 02141 USA. EM lander@broad.mit.edu; mesirov@broad.mit.edu RI Karabulut, Erman/G-6679-2011; OI Mukherjee, Sayan/0000-0002-6715-3920 FU NCI NIH HHS [T32 CA009172] NR 34 TC 8056 Z9 8150 U1 135 U2 555 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 15545 EP 15550 DI 10.1073/pnas.0506580102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 979GC UT WOS:000232929400051 PM 16199517 ER PT J AU Goessel, G Quante, M Hahn, WC Harada, H Heeg, S Suliman, Y Doebele, M von Werder, A Fulda, C Nakagawa, H Rustgi, AK Blum, HE Opitz, OG AF Goessel, G Quante, M Hahn, WC Harada, H Heeg, S Suliman, Y Doebele, M von Werder, A Fulda, C Nakagawa, H Rustgi, AK Blum, HE Opitz, OG TI Creating oral squamous cancer cells: A cellular model of oral-esophageal carcinogenesis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE cyclin D1; epithelial growth factor receptor; in vitro transformation; telomerase; c-myc ID GROWTH-FACTOR RECEPTOR; HUMAN TUMOR-CELLS; CYCLIN D1 ONCOGENE; C-MYC; TRANSFORMING GENES; SIGNALING PATHWAY; EPITHELIAL-CELLS; NECK-CANCER; T-ANTIGEN; IN-VITRO AB Immortalization and malignant transformation are important steps in tumor development. The ability to induce these processes from normal human epithelial cells with genetic alterations frequently found in the corresponding human cancer would significantly enhance our understanding of tumor development. Alterations in several key intracellular regulatory pathways (the pRB, p53, and mitogenic signaling pathways and the telomere maintenance system) appear to be sufficient for the neoplastic transformation of normal human cells. Nevertheless, in vitro transformation models to date depend on viral oncogenes, most prominently the simian virus 40 early region, to induce immortalization and malignant transformation of normal human epithelial cells. Here, we demonstrate a transformation model creating oral-esophageal cancer cells by using a limited set of genetic alterations frequently observed in the corresponding human cancer. In a stepwise model, cyclin D1 overexpression and p53 inactivation led to immortalization of oral keratinocytes. Additional ectopic epithelial growth factor receptor overexpression followed by c-myc overexpression as well as consecutive reactivation of telomerase induced by epithelial growth factor receptor sufficed to transform oral epithelial cells, truly recapitulating the development of the corresponding human disease. C1 Univ Freiburg, Dept Med, D-79116 Freiburg, Germany. Univ Freiburg, Inst Mol Med & Cell Res, D-79116 Freiburg, Germany. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Univ Penn, Div Gastroenterol, Abramson Canc Ctr, Philadelphia, PA 19104 USA. Univ Penn, Dept Genet, Philadelphia, PA 19104 USA. RP Opitz, OG (reprint author), Univ Freiburg, Dept Med 2, Hugstetter Str 55, D-79116 Freiburg, Germany. EM opitz@med1.ukl.uni-freiburg.de NR 53 TC 42 Z9 43 U1 1 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 25 PY 2005 VL 102 IS 43 BP 15599 EP 15604 DI 10.1073/pnas.0409730102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 979GC UT WOS:000232929400060 PM 16239349 ER PT J AU Polli, FE Barton, JJS Cain, MS Thakkar, KN Rauch, SL Manoach, DS AF Polli, FE Barton, JJS Cain, MS Thakkar, KN Rauch, SL Manoach, DS TI Rostral and dorsal anterior cingulate cortex make dissociable contributions during antisaccade error commission SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE default-mode network; performance evaluation; task-induced deactivation; inhibition; cognition ID EVENT-RELATED FMRI; POSITRON EMISSION TOMOGRAPHY; HUMAN CEREBRAL-CORTEX; FUNCTIONAL MRI; BLOOD-FLOW; RESPONSE-INHIBITION; PREFRONTAL CORTEX; BRAIN POTENTIALS; DECISION-MAKING; COUNTING STROOP AB The anterior cingulate cortex (ACC) participates in both performance optimization and evaluation, with dissociable contributions from dorsal (dACC) and rostral (rACC) regions. Deactivation in rACC and other default-mode regions is important for performance optimization, whereas increased rACC and dACC activation contributes to performance evaluation. Errors activate both rACC and dACC. We propose that this activation reflects differential error-related involvement of rACC and dACC during both performance optimization and evaluation, and that these two processes can be distinguished by the timing of their occurrence within a trial. We compared correct and error antisaccade trials. We expected errors to correlate with an early failure of rACC deactivation and increased activation of both rACC and dACC later in the trial. Eighteen healthy subjects performed a series of prosaccade and antisaccade trials during event-related functional MRI. We estimated the hemodynamic responses for error and correct antisaccades using a finite impulse-response model. We examined ACC activity by comparing error and correct antisaccades with a fixation baseline and error to correct antisaccades directly. Compared with correct antisaccades, errors were characterized by an early bilateral failure of deactivation of rACC and other default-mode regions. This difference was significant in rACC. Errors also were associated with increased activity in both rACC and dACC later in the trial. These results show that accurate performance involves deactivation of the rACC and other default mode regions and suggest that both rACC and dACC contribute to the evaluation of error responses. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02215 USA. Suffolk Univ, Dept Psychol, Boston, MA 02114 USA. Univ British Columbia, Dept Neurol, Vancouver, BC V6T 1Z4, Canada. Univ British Columbia, Dept Ophthalmol, Vancouver, BC V6T 1Z4, Canada. Univ British Columbia, Dept Visual Sci, Vancouver, BC V6T 1Z4, Canada. Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Polli, FE (reprint author), CNY 149,Room 2608,13th St, Charlestown, MA 02129 USA. EM fpolli@nmr.mgh.harvard.edu RI Barton, Jason/A-6362-2012; OI Cain, Matthew/0000-0002-3305-0464 FU NIMH NIH HHS [R01 MH067720, R01 MH 67720, F31 MH 72120, F31 MH072120]; NINDS NIH HHS [K08 NS 01920] NR 54 TC 126 Z9 127 U1 3 U2 9 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 15700 EP 15705 DI 10.1073/pnas.0503657102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 979GC UT WOS:000232929400077 PM 16227444 ER PT J AU Albe, E Escalona, E Rajagopal, R Javier, JA Chang, JH Azar, DT AF Albe, E Escalona, E Rajagopal, R Javier, JA Chang, JH Azar, DT TI Proteomic identification of activin receptor-like kinase-1 as a differentially expressed protein during hyaloid vascular system regression SO FEBS LETTERS LA English DT Article DE activin receptor-like kinase-1; hyaloid vascular system regression ID HEREDITARY HEMORRHAGIC TELANGIECTASIA; GROWTH-FACTOR-BETA; TGF-BETA; I RECEPTORS; ANGIOGENESIS; ENDOTHELIUM; NEOVASCULARIZATION; VESSELS; TUMOR; GENE AB The hyaloid vascular system (HVS) is a transient network of capillaries that nourishes the embryonic lens and the primary vitreous of the developing eye. We used proteomic analysis and immunohistochemical staining to identify activin receptor-like kinase-1 (ALK1), a type I receptor for transforming growth factor-beta 1, during the HVS regression phase. In addition, we overexpressed ALK1 in corneas implanted with bFGF (basic fibroblast growth factor) pellets and observed that ALK1 overexpression resulted in inhibition of bFGF-induced corneal neovascularization in vivo. Our data suggest that ALK1 may play a role in HVS regression during ocular development. (c) 2005 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies. C1 Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Schepens Eye Res Inst, Boston, MA 02114 USA. RP Azar, DT (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM dazar@meei.harvard.edu FU NEI NIH HHS [EY10101, EY14048] NR 40 TC 7 Z9 7 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 5481 EP 5486 DI 10.1016/j.febslet.2005.08.078 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 977ST UT WOS:000232824200007 PM 16223497 ER PT J AU Yokoyama, A Somervaille, TCP Smith, KS Rozenblatt-Rosen, O Meyerson, M Cleary, ML AF Yokoyama, A Somervaille, TCP Smith, KS Rozenblatt-Rosen, O Meyerson, M Cleary, ML TI The menin tumor suppressor protein is an essential oncogenic cofactor for MLL-associated leukemogenesis SO CELL LA English DT Article ID HISTONE METHYLTRANSFERASE COMPLEX; MULTIPLE ENDOCRINE NEOPLASIA; LINEAGE-LEUKEMIA GENE; MYELOID PROGENITORS; MUTANT MICE; HEMATOLOGICAL MALIGNANCIES; HEMATOPOIETIC PROGENITORS; DROSOPHILA-TRITHORAX; ONCOPROTEIN MLL; FACTOR JUND AB The Mixed-Lineage Leukemia (MLL) protein is a histone methyltransferase that is mutated in clinically and biologically distinctive subsets of acute leukemia. MLL normally associates with a cohort of highly conserved cofactors to form a macromolecular complex that includes menin, a product of the MEN1 tumor suppressor gene, which is mutated in heritable and sporadic endocrine tumors. We demonstrate here that oncogenic MLL fusion proteins retain an ability to stably associate with menin through a high-affinity, amino-terminal, conserved binding motif and that this interaction is required for the initiation of MLL-mediated leukemogenesis. Furthermore, menin is essential for maintenance of MILL-associated but not other oncogene induced myeloid transformation. Acute genetic ablation of menin reverses aberrant Hox gene expression mediated by MLL-menin promoter-associated complexes, and specifically abrogates the differentiation arrest and oncogenic properties of MLL-transformed leukemic blasts. These results demonstrate that a human oncoprotein is critically dependent on direct physical interaction with a tumor suppressor protein for its oncogenic activity, validate a potential target for molecular therapy, and suggest central roles for menin in altered epigenetic functions underlying the pathogenesis of hematopoietic cancers. C1 Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Dept Pathol, Boston, MA 02115 USA. RP Cleary, ML (reprint author), Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA. EM mcleary@stanford.edu RI Meyerson, Matthew/E-7123-2012; OI Somervaille, Tim/0000-0002-9188-4379 FU NCI NIH HHS [CA116601, CA55029] NR 51 TC 231 Z9 235 U1 0 U2 9 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD OCT 21 PY 2005 VL 123 IS 2 BP 207 EP 218 DI 10.1016/j.cell.2005.09.025 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 977HN UT WOS:000232794100009 PM 16239140 ER PT J AU Baillat, D Hakimi, MA Naar, AM Shilatifard, A Cooch, N Shiekhattar, R AF Baillat, D Hakimi, MA Naar, AM Shilatifard, A Cooch, N Shiekhattar, R TI Integrator, a multiprotein mediator of small nuclear RNA processing, associates with the C-terminal repeat of RNA polymerase II SO CELL LA English DT Article ID SUSCEPTIBILITY GENE BRCA2; U1 SNRNA; 3' END; CELL-GROWTH; DNA-REPAIR; U2 SNRNA; PROTEIN; RAD51; INTERACTS; STABILITY AB The C-terminal domain (CTD) of RNA polymerase 11 (RNAPII) is an essential component of transcriptional regulation and RNA processing of protein-coding genes. A large body of data also implicates the CTD in the transcription and processing of RNAPII-mediated small nuclear RNAs (snRNAs). However, the identity of the complex (or complexes) that associates with the CTD and mediates the processing of snRNAs has remained elusive. Here, we describe an RNA polymerase 11 complex that contains at least 12 novel subunits, termed the Integrator, in addition to core RNAPII subunits. Two of the Integrator subunits display similarities to the subunits of the cleavage and polyadenylation specificity factor (CPSF) complex. We show that Integrator is recruited to the U1 and U2 snRNA genes and mediates the snRNAs' 3' end processing. The Integrator complex is evolutionarily conserved in metazoans and directly interacts with the C-terminal domain of the RNA polymerase 11 largest subunit. C1 Wistar Inst Anat & Biol, Philadelphia, PA 19104 USA. Univ Grenoble 1, CNRS, UMR 5163, F-38700 La Tronche, France. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. St Louis Univ, Hlth Sci Ctr, Dept Biochem & Mol Biol, St Louis, MO 63104 USA. RP Shiekhattar, R (reprint author), Wistar Inst Anat & Biol, 3601 Spruce St, Philadelphia, PA 19104 USA. EM shiekhattar@wistar.upenn.edu RI HAKIMI, Mohamed-Ali/F-9806-2014; OI HAKIMI, Mohamed-ali/0000-0002-2547-8233 NR 33 TC 197 Z9 216 U1 1 U2 15 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD OCT 21 PY 2005 VL 123 IS 2 BP 265 EP 276 DI 10.1016/j.cell.2005.08.019 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 977HN UT WOS:000232794100013 PM 16239144 ER PT J AU Kocks, C Cho, JH Nehme, N Ulvila, J Pearson, AM Meister, M Strom, C Conto, SL Hetru, C Stuart, LM Stehle, T Hoffmann, JA Reichhart, JM Ferrandon, D Ramet, M Ezekowitz, RAB AF Kocks, C Cho, JH Nehme, N Ulvila, J Pearson, AM Meister, M Strom, C Conto, SL Hetru, C Stuart, LM Stehle, T Hoffmann, JA Reichhart, JM Ferrandon, D Ramet, M Ezekowitz, RAB TI Eater, a transmembrane protein mediating phagocytosis of bacterial pathogens in Drosophila SO CELL LA English DT Article ID SCAVENGER RECEPTOR; INNATE IMMUNITY; CELL-DEATH; RECOGNITION; HEMOCYTES; IDENTIFICATION; HEMATOPOIESIS; MECHANISMS; ENGULFMENT; COMPLEXITY AB Phagocytosis is a complex, evolutionarily conserved process that plays a central role in host defense against infection. We have identified a predicted transmembrane protein, Eater, which is involved in phagocytosis in Drosophila. Transcriptional silencing of the eater gene in a macrophage cell line led to a significant reduction in the binding and internalization of bacteria. Moreover, the N terminus of the Eater protein mediated direct microbial binding which could be inhibited with scavenger receptor ligands, acetylated, and oxidized low-density lipoprotein. In vivo, eater expression was restricted to blood cells. Files lacking the eater gene displayed normal responses in NF-kappa B-like Toll and IMD signaling pathways but showed impaired phagocytosis and decreased survival after bacterial infection. Our results suggest that Eater is a major phagocytic receptor for a broad range of bacterial pathogens in Drosophila and provide a powerful model to address the role of phagocytosis in vivo. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Lab Dev Immunol,Dept Pediat, Boston, MA 02114 USA. Inst Biol Mol & Cellulaire, Ctr Natl Rech Sci, UPR9022, F-67084 Strasbourg, France. Oulu Univ, Dept Pediat, SF-90220 Oulu, Finland. Oulu Univ, Bioctr, SF-90220 Oulu, Finland. Tampere Univ, Inst Med Technol, FIN-33101 Tampere, Finland. Tampere Univ Hosp, Dept Pediat, Tampere, Finland. RP Kocks, C (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Lab Dev Immunol,Dept Pediat, Boston, MA 02114 USA. EM christine_kocks@hms.harvard.edu OI FERRANDON, Dominique/0000-0001-7680-7773 FU NIAID NIH HHS [P01 AI 44220] NR 41 TC 199 Z9 204 U1 4 U2 18 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD OCT 21 PY 2005 VL 123 IS 2 BP 335 EP 346 DI 10.1016/j.cell.2005.08.034 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 977HN UT WOS:000232794100018 PM 16239149 ER PT J AU Kim, K Kim, JH Lee, J Jin, HM Lee, SH Fisher, DE Kook, H Kim, KK Choi, YW Kim, NS AF Kim, K Kim, JH Lee, J Jin, HM Lee, SH Fisher, DE Kook, H Kim, KK Choi, YW Kim, NS TI Nuclear factor of activated T cells c1 induces osteoclast-associated receptor gene expression during tumor necrosis factor-related activation-induced cytokine-mediated osteoclastogenesis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MICROPHTHALMIA TRANSCRIPTION FACTOR; FCR-GAMMA; KAPPA-B; TERMINAL DIFFERENTIATION; SIGNAL-TRANSDUCTION; BONE-RESORPTION; PROTEIN-KINASE; FACTOR FAMILY; LIGAND; OSTEOPETROSIS AB Osteoclast differentiation from hematopoietic precursors is controlled by the tumor necrosis factor family member tumor necrosis factor-related activation-induced cytokine (TRANCE) via induction of various transcription factors, including nuclear factor of activated T cells (NFAT) c1. During osteoclast differentiation, NFATc1 is further activated via calcium signaling when costimulatory receptors expressed on osteoclast precursors, such as osteoclast-associated receptor (OSCAR), are stimulated. Here we show that NFATc1 expression precedes that of OSCAR during TRANCE-mediated osteoclastogenesis and that inhibition of NFATc1 by cyclosporin A abolishes TRANCE-induced OSCAR expression and subsequent osteoclast differentiation. Moreover, we show that the 1.0-kb promoter region of the OSCAR gene contains three potential NFATc1-binding sites. Induction of an OSCAR promoter-luciferase reporter is significantly increased when transiently transfected into 293T cells in combination with NFATc1 expression plasmid. Deletion and site-directed mutant constructs confirmed that NFATc1-binding sites are both functional and NFATc1-specific. Furthermore, NFATc1 synergistically activates an OSCAR reporter construct together with microphthalmia transcription factor and PU.1, transcription factors previously shown to be critical for osteoclast differentiation. In addition, a plasmid expressing constitutively active MAP kinase kinase 6 enhances the transactivation activity of NFATc1/microphthalmia transcription factor/PU.1 on the OSCAR promoter. Taken together, our results indicate that NFATc1 is an important transcription factor in the induction of OSCAR during osteoclastogenesis. Elucidation of NFATc1 as a transcription factor for OSCAR expression implies the presence of a positive feedback circuit of TRANCE-induced activation of NFATc1, involving NFATc1-mediated OSCAR expression and its subsequent activation of NFATc1, necessary for efficient differentiation of osteoclasts. C1 Chonnam Natl Univ, Sch Med, Med Res Ctr Gene Regulat, Dong Ku 501746, Gwangju, South Korea. Univ Penn, Sch Med, Dept Pathol & Lab Med, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Kim, NS (reprint author), Chonnam Natl Univ, Sch Med, Med Res Ctr Gene Regulat, Hak Dong 5, Dong Ku 501746, Gwangju, South Korea. EM nacksung@jnu.ac.kr FU NIAMS NIH HHS [AR48521, AR49078] NR 32 TC 120 Z9 124 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 21 PY 2005 VL 280 IS 42 BP 35209 EP 35216 DI 10.1074/jbc.M505815200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 973ZN UT WOS:000232561200018 PM 16109714 ER PT J AU Robinson, MA Park, S Sun, ZYJ Silver, PA Wagner, G Hogle, JM AF Robinson, MA Park, S Sun, ZYJ Silver, PA Wagner, G Hogle, JM TI Multiple conformations in the ligand-binding site of the yeast nuclear pore-targeting domain of Nup116p SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MACROMOLECULAR STRUCTURE; NUCLEOPORIN NUP145P; BIOGENESIS PATHWAY; PROTEIN STRUCTURES; COMPLEX; NUP98; NMR; DYNAMICS; PROGRAM; ARCHITECTURE AB The yeast nucleoporin Nup116p plays an important role in mRNA export and protein transport. We have determined the solution structure of the C- terminal 147 residues of this protein, the region responsible for targeting the protein to the nuclear pore complex ( NPC). The structure of Nup116p- C consists of a large beta- sheet sandwiched against a smaller one, flanked on both sides by alpha- helical stretches, similar to the structure of its human homolog, NUP98. In unliganded form, Nup116p- C exhibits evidence of exchange among multiple conformations, raising the intriguing possibility that it may adopt distinct conformations when bound to different partners in the NPC. We have additionally shown that a peptide from the N terminus of the nucleoporin Nup145p- C binds Nup116p- C. This previously unknown interaction may explain the unusual asymmetric localization pattern of Nup116p in the NPC. Strikingly, the exchange phenomenon observed in the unbound state is greatly reduced in the corresponding spectra of peptide-bound Nup116p- C, suggesting that the binding interaction stabilizes the domain conformation. This study offers a high resolution view of a yeast nucleoporin structural domain and may provide insights into NPC architecture and function. C1 Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Comm Higher Degrees Biophys, Cambridge, MA 02138 USA. Inha Univ, Coll Med, Dept Biochem, Inchon 400712, South Korea. RP Wagner, G (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, 240 Longwood Ave, Boston, MA 02115 USA. EM gerhard_wagner@hms.harvard.edu; james_hogle@hms.harvard.edu OI Hogle, James/0000-0002-3655-1504 FU NCI NIH HHS [CA68262]; NIAID NIH HHS [R01 AI020566]; NIGMS NIH HHS [GM36373, GM47467] NR 40 TC 14 Z9 14 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 21 PY 2005 VL 280 IS 42 BP 35723 EP 35732 DI 10.1074/jbc.M505068200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 973ZN UT WOS:000232561200075 PM 16105837 ER PT J AU Casal, A Sumen, C Reddy, TE Alber, MS Lee, PP AF Casal, A Sumen, C Reddy, TE Alber, MS Lee, PP TI Agent-based modeling of the context dependency in T cell recognition SO JOURNAL OF THEORETICAL BIOLOGY LA English DT Article DE T cell recognition; receptor clustering; immune synapse; agent-based simulation; systems biology ID IMMUNOLOGICAL SYNAPSE FORMATION; MHC CLASS-II; SIGNAL-TRANSDUCTION; LIGAND RECOGNITION; ANTAGONIST LIGANDS; RECEPTOR; ANTIGEN; ACTIVATION; PEPTIDE; TCR AB Antigen recognition by T cells is a key event in the adaptive immune response. T cells scan the surface of antigen-presenting cells (APCs) or target cells for specific peptides bound to MHC molecules. In the physiological setting, a typical APC presents tens of thousands of diverse endogenous self-derived peptides complexed to MHC (pMHC complexes). When 'foreign' peptides are presented, they constitute a small fraction of the total surface peptide repertoire. As T cells seem to be capable of discerning minute amounts of 'foreign' peptides among a complex background of self-peptides, endogenous peptides are generally assumed to play no role in recognition. However, recent results suggest that these background peptides may alter the sensitivity of T cells to foreign peptides. Current experimental limitations preclude analysis of peptide mixtures approaching physiological complexity, making it difficult to further address the role of complex background peptides. In this paper, we present a computational model to test how complex, varied peptide populations on an APC could potentially modulate a T cell's ability to detect the presence of small numbers of agonist peptides among a diverse population. We use the model to investigate the notion that under physiological conditions, T cell recognition of foreign peptides is context dependent, that is, T cells process signals gathered from all pMHC interactions, not just from a few agonist peptides while ignoring all others. (c) 2005 Elsevier Ltd. All rights reserved. C1 Univ Notre Dame, Dept Math, Notre Dame, IN 46556 USA. Univ Notre Dame, Ctr Study Biocomplex, Notre Dame, IN 46556 USA. Stanford Univ, Dept Med, Stanford, CA 94305 USA. Harvard Univ, Sch Med, Ctr Blood Res, Boston, MA 02115 USA. Boston Univ, Program Bioinformat & Syst Biol, Boston, MA 02215 USA. RP Alber, MS (reprint author), Univ Notre Dame, Dept Math, 255 Hurley Bldg, Notre Dame, IN 46556 USA. EM malber@nd.edu; ppl@stanford.edu OI Reddy, Timothy/0000-0002-7629-061X FU NCI NIH HHS [R01 CA 090809] NR 50 TC 27 Z9 27 U1 0 U2 2 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-5193 J9 J THEOR BIOL JI J. Theor. Biol. PD OCT 21 PY 2005 VL 236 IS 4 BP 376 EP 391 DI 10.1016/j.jtbi.2005.03.019 PG 16 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA 961AD UT WOS:000231633400003 PM 15899504 ER PT J AU Ganesh, S Tsurutani, N Amano, K Mittal, S Uchikawa, C Delgado-Escueta, AV Yamakawa, K AF Ganesh, S Tsurutani, N Amano, K Mittal, S Uchikawa, C Delgado-Escueta, AV Yamakawa, K TI Transcriptional profiling of a mouse model for Lafora disease reveals dysregulation of genes involved in the expression and modification of proteins SO NEUROSCIENCE LETTERS LA English DT Article DE epilepsy; microarray; neuronal death; phosphatase; post-translation modification of proteins; polyglucosan inclusions ID PROGRESSIVE MYOCLONUS EPILEPSY; EPM2A GENE; CELL-DEATH; SUBUNIT; NEURODEGENERATION; INTERACTS; PROMOTES; PRODUCT; GLUCOSE; DOMAIN AB Lafora's progressive myoclonus epilepsy (Lafora disease: LD) is caused by mutations in the EPM2A or NHLRC1 gene, but cellular mechanisms of the pathogenesis remain unclear. In an attempt to understand and elucidate the disease pathway, we have investigated the global gene expression profile in a mouse model for LD that developed a phenotype similar to that observed in human patients, including presence of Lafora bodies, neurodegeneration and profound neurological disturbances. We found 62 differentially expressed genes in the Epm2a knockout mice brains. These genes encode factors involved in protein catabolism, phosphatase, transcription factors, and molecules involved in protein translation, and homeostasis. The two largest functional groups of mRNAs that showed altered expression were predicted to be involved in post-translational modification of proteins and transcriptional regulation, suggesting that defects in protein activity and/or turnover may be the key trigger in the pathophysiology of LD. Furthermore we show that changes in gene expression are not limited to brain and are seen in other organs that develop Lafora bodies. Our study may provide valuable insights into the pathophysiology of LD and may aid in developing potential therapeutic targets. (C) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Indian Inst Technol, Dept Biol Sci & Bioengn, Kanpur 208016, Uttar Pradesh, India. RIKEN, Brain Sci Inst, Neurogenet Lab, Wako, Saitama 3510198, Japan. Univ Calif Los Angeles, Sch Med, Comprehens Epilepsy Program, Epilepsy Genet Genom Labs, Los Angeles, CA USA. VA GLAHS W Los Angeles Med Ctr, Los Angeles, CA USA. RP Ganesh, S (reprint author), Indian Inst Technol, Dept Biol Sci & Bioengn, Kanpur 208016, Uttar Pradesh, India. EM sganesh@iitk.ac.in; yamakawa@brain.riken.go.jp RI Ganesh, Subramniam/B-4131-2009; Yamakawa, Kazuhiro/N-5050-2015; OI Delgado-Escueta, Antonio V./0000-0002-1581-6999 FU NINDS NIH HHS [NS42376] NR 25 TC 3 Z9 4 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD OCT 21 PY 2005 VL 387 IS 2 BP 62 EP 67 DI 10.1016/j.neulet.2005.07.002 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 958YI UT WOS:000231483700002 PM 16084644 ER PT J AU Neicu, T Aljarrah, KM Jiang, SB AF Neicu, T Aljarrah, KM Jiang, SB TI A software tool for 2D/3D visualization and analysis of phase-space data generated by Monte Carlo modelling of medical linear accelerators SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID TREATMENT PLANNING SYSTEM; PHOTON-BEAM; ELECTRON-BEAM; DOSE CALCULATIONS; SIMULATION; RADIOTHERAPY; RADIATION; CODE; CONTAMINATION; PARAMETERS AB A computer program has been developed for novel 2D/3D visualization and analysis of the phase-space parameters of Monte Carlo simulations of medical accelerator radiation beams. The software is written in the IDL language and reads the phase-space data generated in the BEAMnrc/BEAM Monte Carlo code format. Contour and colour-wash plots of the fluence, mean energy, energy fluence, mean angle, spectra distribution, energy fluence distribution, angular distribution, and slices and projections of the 3D ZLAST distribution can be calculated and displayed. Based on our experience of using it at Massachusetts General Hospital, the software has proven to be a useful tool for analysis and verification of the Monte Carlo generated phase-space files. The software is in the public domain. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Jiang, SB (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. EM jiang.steve@mgh.harvard.edu NR 48 TC 0 Z9 0 U1 0 U2 0 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD OCT 21 PY 2005 VL 50 IS 20 BP N257 EP N267 DI 10.1088/0031-9155/50/20/N02 PG 11 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 991EG UT WOS:000233794500014 PM 16204867 ER PT J AU Talcott, JA AF Talcott, JA TI Rebalancing ratios and improving impressions: Later thoughts from the prostate cancer prevention trial investigators SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Editorial Material ID EARLY BREAST-CANCER; FINASTERIDE; TAMOXIFEN; THERAPY C1 Massachusetts Gen Hosp, Ctr Canc, Ctr Outcomes Res, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Talcott, JA (reprint author), Massachusetts Gen Hosp, Ctr Canc, Ctr Outcomes Res, Boston, MA 02114 USA. NR 11 TC 3 Z9 4 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 7388 EP 7390 DI 10.1200/JCO.2005.07.909 PG 3 WC Oncology SC Oncology GA 979IJ UT WOS:000232935300005 PM 16186587 ER PT J AU Ferrone, CR Kattan, MW Tomlinson, JS Thayer, SP Brennan, MF Warshaw, AL AF Ferrone, CR Kattan, MW Tomlinson, JS Thayer, SP Brennan, MF Warshaw, AL TI Validation of a postresection pancreatic adenocarcinorna nomogram for disease-specific survival SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID POSTOPERATIVE NOMOGRAM; RESECTION; CANCER; CARCINOMA AB Purpose Nomograms are statistically based tools that provide the overall probability of a specific outcome. They have shown better individual discrimination than the current TNM staging system in numerous patient tumor models. The pancreatic nomogram combines individual clinicopathologic and operative data to predict disease-specific survival at 1, 2, and 3 years from initial resection. A single US institution database was used to test the validity of the pancreatic adenocarcinoma nomogram established at Memorial Sloan-Kettering Cancer Center. Patients and Methods The nomogram was created from a prospective pancreatic adenocarcinoma database that included 555 consecutive patients between October 1983 and April 2000. The nomogram was validated by an external patient cohort from a retrospective pancreatic adenocarcinoma database at Massachusetts General Hospital that included 424 consecutive patients be tween January 1985 and December 2003. Results Of the 424 patients, 375 had all variables documented. At last follow-up, 99 patients were alive, with a median follow-up time of 27 months (range, 2 to 151 months). The 1-, 2-, and 3-year disease-specific survival rates were 68% (95% CI, 63% to 72%), 39% (95% CI, 34% to 44%), and 27% (95% CI, 23% to 32%), respectively. The nomogram concordance index was 0.62 compared with 0.59 with the American Joint Committee on Cancer (AJCC) stage (P = .004). This suggests that the nomogram discriminates disease-specific survival better than the AJCC staging system. Conclusion The pancreatic cancer nomogram provides more accurate survival predictions than the AJCC staging system when applied to an external patient cohort. The nomogram may aid in more accurately counseling patients and in better stratifying patients for clinical trials and molecular tumor analysis. C1 Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10021 USA. Cleveland Clin, Dept Quantitat Hlth Sci, Cleveland, OH 44106 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Ferrone, CR (reprint author), Mem Sloan Kettering Canc Ctr, Dept Surg, 1275 York Ave,Box 435, New York, NY 10021 USA. EM ferronec@mskee.org FU NIDDK NIH HHS [K08 DK071329] NR 14 TC 48 Z9 49 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 7529 EP 7535 DI 10.1200/JCO.2005.01.8101 PG 7 WC Oncology SC Oncology GA 979IJ UT WOS:000232935300026 PM 16234519 ER PT J AU Lyman, GH Giuliano, AE Somerfield, MR Benson, AB Bodurka, DC Burstein, HJ Benson, AB Bodurka, DC Burstein, HJ Cochran, AJ Cody, HS Edge, SB Galper, S Hayman, JA Kim, TY Perkins, CL Podoloff, DA Sivasubramaniam, VH Turner, RR Wahl, R Weaver, DL Wolff, AC Winer, EP AF Lyman, GH Giuliano, AE Somerfield, MR Benson, AB Bodurka, DC Burstein, HJ Benson, AB Bodurka, DC Burstein, HJ Cochran, AJ Cody, HS Edge, SB Galper, S Hayman, JA Kim, TY Perkins, CL Podoloff, DA Sivasubramaniam, VH Turner, RR Wahl, R Weaver, DL Wolff, AC Winer, EP TI American Society of Clinical Oncology guideline recommendations for sentinel lymph node biopsy in early-stage breast cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID ROUTINE AXILLARY DISSECTION; INTERNAL MAMMARY NODES; ISOSULFAN BLUE-DYE; PREOPERATIVE CHEMOTHERAPY; NEOADJUVANT CHEMOTHERAPY; PROGNOSTIC-SIGNIFICANCE; PERITUMORAL INJECTION; MULTIVARIATE-ANALYSIS; SUBAREOLAR INJECTION; PREDICTIVE FACTORS AB Purpose To develop a guideline for the use of sentinel node biopsy (SNB) in early stage breast cancer. Methods An American Society of Clinical Oncology (ASCO) Expert Panel conducted a systematic review of the literature available through February 2004 on the use of SNB in early-stage breast cancer. The panel developed a guideline for clinicians and patients regarding the appropriate use of a sentinel lymph node identification and sampling procedure from hereon referred to as SNB. The guideline was reviewed by selected experts in the field and the ASCO Health Services Committee and was approved by the ASCO Board of Directors. Results The literature review identified one published prospective randomized controlled trial in which SNB was compared with axillary lymph node dissection (ALND), four limited meta-analyses, and 69 published single-institution and multicenter trials in which the test performance of SNB was evaluated with respect to the results of ALND (completion axillary dissection). There are currently no data on the effect of SLN biopsy on long-term survival of patients with breast cancer. However, a review of the available evidence demonstrates that, when performed by experienced clinicians, SNB appears to be a safe and acceptably accurate method for identifying early-stage breast cancer without involvement of the axillary lymph nodes. Conclusion SNB is an appropriate initial alternative to routine staging ALND for patients with early-stage breast cancer with clinically negative axillary nodes. Completion ALND remains standard treatment for patients with axillary metastases identified on SNB. Appropriately identified patients with negative results of SNB, when done under the direction of an experienced surgeon, need not have completion ALND. Isolated cancer cells detected by pathologic examination of the SLN with use of specialized techniques are currently of unknown clinical significance. Although such specialized techniques are often used, they are not a required part of SLN evaluation for breast cancer at this time. Data suggest that SNB is associated with less morbidity than ALND, but the comparative effects of these two approaches on tumor recurrence or patient survival are unknown. C1 Univ Rochester, Sch Med & Dent, Rochester, NY USA. John Wayne Canc Inst, Santa Monica, CA USA. NW Univ, Evanston, IL USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Tufts Univ, New England Med Ctr, Boston, MA 02111 USA. Susan G Komen Breast Canc Fdn, Dallas, TX USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Kentucky, Lexington, KY USA. St Johns Hlth Ctr, Santa Monica, CA USA. Johns Hopkins Univ, Baltimore, MD USA. Univ Vermont, Coll Med, Burlington, VT USA. Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA. RP Lyman, GH (reprint author), Amer Soc Clin Oncol, 1900 Duke St,Suite 200, Alexandria, VA 22314 USA. OI Wolff, Antonio/0000-0003-3734-1063 NR 146 TC 930 Z9 987 U1 2 U2 32 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 7703 EP 7720 DI 10.1200/JCO.2005.08.001 PG 18 WC Oncology SC Oncology GA 979IJ UT WOS:000232935300046 PM 16157938 ER PT J AU Warden, SJ Bliziotes, MM Wiren, KM Eshleman, AJ Turner, CH AF Warden, SJ Bliziotes, MM Wiren, KM Eshleman, AJ Turner, CH TI Neural regulation of bone and the skeletal effects of serotonin (5-hydroxytryptamine) SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Review DE bone density; leptin; neurotransmitter; osteoporosis; SSRI ID GENE-RELATED PEPTIDE; SYMPATHETIC-NERVOUS-SYSTEM; BETA-BLOCKER USE; REUPTAKE INHIBITORS; MINERAL DENSITY; SUBSTANCE-P; MAJOR DEPRESSION; OLDER WOMEN; ANTIDEPRESSANT MEDICATIONS; TRICYCLIC ANTIDEPRESSANTS AB There is increasing evidence for a contribution of the neural system to the regulation of bone metabolism. The skeleton is richly innervated by both sympathetic and sensory neurons. While these nerves serve sensory and vascular functions, they are also being found to influence bone cell activities. The most convincing evidence for this has been provided by studies into the skeletal effects of the hormone leptin, which has been shown to centrally regulate bone mass, and through studies into the skeletal effects of hypothalamic neuropeptide Y2 and Y4 receptors. This paper discusses recent evidence for the neural regulation of bone metabolism and, in particular, the potential role of the neurotransmitter serotonin (5-hydroxytryptamine, 5-HT). Recent studies have demonstrated the presence of functional pathways in bone for both responding to and regulating the uptake of 5-HT. This is of high clinical relevance given the role of the serotonergic system in affective disorders, and the wide use of pharmacological agents that target the 5-HT system to manage these disorders. Initial data suggest that exposure to these agents at different stages during the lifespan may have significant effects on the skeleton. (c) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Indiana Univ, Dept Phys Therapy, Indianapolis, IN 46202 USA. Portland Vet Affairs Med Ctr, Portland, OR USA. Oregon Hlth Sci Univ, Dept Med, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Behav Neurosci, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Psychiat, Portland, OR 97201 USA. Indiana Univ Purdue Univ, Dept Biomed Engn, Indianapolis, IN 46202 USA. RP Warden, SJ (reprint author), Indiana Univ, Dept Phys Therapy, 1140 W Michigan St,CF-326, Indianapolis, IN 46202 USA. EM stwarden@iupui.edu RI Warden, Stuart/C-5287-2012; OI Wiren, Kristine/0000-0002-6159-4450; Warden, Stuart/0000-0002-6415-4936 FU NIA NIH HHS [P01AG18397]; NIAMS NIH HHS [R01 AR046530] NR 120 TC 44 Z9 47 U1 3 U2 7 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD OCT 20 PY 2005 VL 242 IS 1-2 BP 1 EP 9 DI 10.1016/j.mce.2005.06.005 PG 9 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 978BK UT WOS:000232847000001 PM 16085354 ER PT J AU Rual, JF Venkatesan, K Hao, T Hirozane-Kishikawa, T Dricot, A Li, N Berriz, GF Gibbons, FD Dreze, M Ayivi-Guedehoussou, N Klitgord, N Simon, C Boxem, M Milstein, S Rosenberg, J Goldberg, DS Zhang, LV Wong, SL Franklin, G Li, SM Albala, JS Lim, JH Fraughton, C Llamosas, E Cevik, S Bex, C Lamesch, P Sikorski, RS Vandenhaute, J Zoghbi, HY Smolyar, A Bosak, S Sequerra, R Doucette-Stamm, L Cusick, ME Hill, DE Roth, FP Vidal, M AF Rual, JF Venkatesan, K Hao, T Hirozane-Kishikawa, T Dricot, A Li, N Berriz, GF Gibbons, FD Dreze, M Ayivi-Guedehoussou, N Klitgord, N Simon, C Boxem, M Milstein, S Rosenberg, J Goldberg, DS Zhang, LV Wong, SL Franklin, G Li, SM Albala, JS Lim, JH Fraughton, C Llamosas, E Cevik, S Bex, C Lamesch, P Sikorski, RS Vandenhaute, J Zoghbi, HY Smolyar, A Bosak, S Sequerra, R Doucette-Stamm, L Cusick, ME Hill, DE Roth, FP Vidal, M TI Towards a proteome-scale map of the human protein-protein interaction network SO NATURE LA English DT Article ID ORFEOME VERSION 1.1; INTERACTION DATABASE; 2-HYBRID SCREENS; C-ELEGANS; GENOME; ANNOTATION; RESOURCE; PLATFORM; BIOLOGY; GENES AB Systematic mapping of protein-protein interactions, or 'interactome' mapping, was initiated in model organisms, starting with defined biological processes(1,2) and then expanding to the scale of the proteome(3-7). Although far from complete, such maps have revealed global topological and dynamic features of interactome networks that relate to known biological properties(8,9), suggesting that a human interactome map will provide insight into development and disease mechanisms at a systems level. Here we describe an initial version of a proteome-scale map of human binary protein-protein interactions. Using a stringent, high-throughput yeast two-hybrid system, we tested pairwise interactions among the products of similar to 8,100 currently available Gateway-cloned open reading frames and detected similar to 2,800 interactions. This data set, called CCSB-HI1, has a verification rate of similar to 78% as revealed by an independent co-affinity purification assay, and correlates significantly with other biological attributes. The CCSB-HI1 data set increases by similar to 70% the set of available binary interactions within the tested space and reveals more than 300 new connections to over 100 disease-associated proteins. This work represents an important step towards a systematic and comprehensive human interactome project. C1 Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Fac Notre Dame Paix, Unite Rech Biol Mol, B-5000 Namur, Belgium. Howard Hughes Med Inst, Houston, TX 77030 USA. Baylor Univ, Dept Pediat, Houston, TX 77030 USA. Baylor Univ, Dept Neurol, Houston, TX 77030 USA. Baylor Univ, Dept Neurosci, Houston, TX 77030 USA. Baylor Univ, Dept Mol & Human Genet, Houston, TX 77030 USA. Arcbay Inc, Boston, MA 01915 USA. Agencourt Biosci Corp, Beverly, MA 01915 USA. RP Vidal, M (reprint author), Dana Farber Canc Inst, Ctr Canc Syst Biol, 44 Binney St, Boston, MA 02115 USA. EM david_hill@dfci.harvard.edu; fritz_roth@hms.harvard.edu; marc_vidal@dfci.harvard.edu RI Klitgord, Niels/B-5121-2009; Boxem, Mike/B-8857-2011; Hill, David/B-6617-2011; Roth, Frederick/H-6308-2011; OI Boxem, Mike/0000-0003-3966-4173; Cevik, Sebiha/0000-0002-0935-1929; , /0000-0001-7002-8488; Rual, Jean-Francois/0000-0003-4465-8819; Roth, Frederick/0000-0002-6628-649X FU NCI NIH HHS [R33 CA132073]; NHGRI NIH HHS [P50 HG004233, R01 HG001715, RC4 HG006066, U01 HG001715]; NHLBI NIH HHS [U01 HL098166] NR 30 TC 1580 Z9 1650 U1 25 U2 178 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 1173 EP 1178 DI 10.1038/nature04209 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 975KD UT WOS:000232660500048 PM 16189514 ER PT J AU Burstein, HJ AF Burstein, HJ TI The distinctive nature of HER2-positive breast cancers SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Burstein, HJ (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, 75 Francis St, Boston, MA 02115 USA. NR 4 TC 166 Z9 177 U1 2 U2 15 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 1652 EP 1654 DI 10.1056/NEJMp058197 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 975IC UT WOS:000232653200004 PM 16236735 ER PT J AU Piccart-Gebhart, MJ Procter, M Leyland-Jones, B Goldhirsch, A Untch, M Smith, I Gianni, L Baselga, J Bell, R Jackisch, C Cameron, D Dowsett, M Barrios, CH Steger, G Huang, CS Andersson, M Inbar, M Lichinitser, M Lang, I Nitz, U Iwata, H Thomssen, C Lohrisch, C Suter, TM Ruschoff, J Suto, T Greatorex, V Ward, C Straehle, C McFadden, E Dolci, MS Gelber, RD AF Piccart-Gebhart, MJ Procter, M Leyland-Jones, B Goldhirsch, A Untch, M Smith, I Gianni, L Baselga, J Bell, R Jackisch, C Cameron, D Dowsett, M Barrios, CH Steger, G Huang, CS Andersson, M Inbar, M Lichinitser, M Lang, I Nitz, U Iwata, H Thomssen, C Lohrisch, C Suter, TM Ruschoff, J Suto, T Greatorex, V Ward, C Straehle, C McFadden, E Dolci, MS Gelber, RD CA HERA Trial Study Team TI Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID HER2/NEU-OVEREXPRESSING METASTATIC BREAST; MONOCLONAL-ANTIBODY; PHASE-II; 1ST-LINE TREATMENT; MAMMARY-CARCINOMA; NEU ONCOGENE; RECEPTOR; THERAPY; EFFICACY; SAFETY AB BACKGROUND: Trastuzumab, a recombinant monoclonal antibody against HER2, has clinical activity in advanced breast cancer that overexpresses HER2. We investigated its efficacy and safety after excision of early-stage breast cancer and completion of chemotherapy. METHODS: This international, multicenter, randomized trial compared one or two years of trastuzumab given every three weeks with observation in patients with HER2-positive and either node-negative or node-positive breast cancer who had completed locoregional therapy and at least four cycles of neoadjuvant or adjuvant chemotherapy. RESULTS: Data were available for 1694 women randomly assigned to two years of treatment with trastuzumab, 1694 women assigned to one year of trastuzumab, and 1693 women assigned to observation. We report here the results only of treatment with trastuzumab for one year or observation. At the first planned interim analysis (median follow-up of one year), 347 events (recurrence of breast cancer, contralateral breast cancer, second nonbreast malignant disease, or death) were observed: 127 events in the trastuzumab group and 220 in the observation group. The unadjusted hazard ratio for an event in the trastuzumab group, as compared with the observation group, was 0.54 (95 percent confidence interval, 0.43 to 0.67; P<0.0001 by the log-rank test, crossing the interim analysis boundary), representing an absolute benefit in terms of disease-free survival at two years of 8.4 percentage points. Overall survival in the two groups was not significantly different (29 deaths with trastuzumab vs. 37 with observation). Severe cardiotoxicity developed in 0.5 percent of the women who were treated with trastuzumab. CONCLUSIONS: One year of treatment with trastuzumab after adjuvant chemotherapy significantly improves disease-free survival among women with HER2-positive breast cancer. C1 Univ Libre Bruxelles, Inst Jules Bordet, Dept Med, B-1000 Brussels, Belgium. Univ Libre Bruxelles, Inst Jules Bordet, Breast Int Grp Secretariat, B-1000 Brussels, Belgium. Univ Libre Bruxelles, Inst Jules Bordet, Breast European Adjuvant Study Team Data Ctr, B-1000 Brussels, Belgium. Frontier Sci Scotland, Kingussie, Scotland. McGill Univ, Dept Oncol, Gerald Bronfman Ctr Clin Res Oncol, Montreal, PQ, Canada. European Inst Oncol, Dept Med, Milan, Italy. Oncol Inst So Switzerland, Bellinzona, Switzerland. Univ Munich, Klin Frauenheilkunde & Geburtshilfe, Munich, Germany. Royal Marsden Hosp, Breast Unit, London SW3 6JJ, England. Inst Canc Res, London SW3 6JB, England. Ist Nazl Studie & Cura Tumori, Milan, Italy. Vall Hebron Univ, Med Oncol Serv, Barcelona, Spain. Geelong Hosp, Andrew Love Canc Ctr, Geelong, Vic, Australia. Univ Marburg, Dept Gynecol, Marburg, Germany. Western Gen Hosp, Dept Oncol, Edinburgh EH4 2XU, Midlothian, Scotland. Royal Marsden Natl Hlth Serv Trust, Dept Acad Biochem, London, England. Pontificia Univ Catolica Rio Grande Sul, Hosp Sao Lucas, Sch Med, Porto Alegre, RS, Brazil. Med Univ Vienna, Dept Internal Med, Vienna, Austria. Natl Taiwan Univ Hosp, Dept Surg, Taipei 100, Taiwan. Natl Taiwan Univ, Coll Med, Taipei, Taiwan. Rigshosp, Univ Hosp, Finsen Ctr, Dept Oncol, DK-2100 Copenhagen, Denmark. Tel Aviv Sourasky Med Ctr, Tel Aviv, Israel. NN Blokhin Canc Res Ctr, Moscow, Russia. Natl Inst Oncol, Dept Oncol, Budapest, Hungary. Univ Dusseldorf, Frauenklin, D-4000 Dusseldorf, Germany. Aichi Canc Ctr, Dept Breast Oncol, Aichi, Japan. Univ Klinikum Hamburg Eppendorf, Klin & Poliklin Gynakol, Hamburg, Germany. British Columbia Canc Agcy, Vancouver Ctr, Dept Med Oncol, Vancouver, BC V5Z 4E6, Canada. Swiss Cardiovasc Ctr, Bern, Switzerland. Klinikum Kassel, Inst Pathol, Kassel, Germany. F Hoffmann La Roche, Basel, Switzerland. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. RP Piccart-Gebhart, MJ (reprint author), Univ Libre Bruxelles, Inst Jules Bordet, Dept Med, Blvd Waterloo 125, B-1000 Brussels, Belgium. EM martine.piccart@bordet.be RI Barrios, Carlos/G-8525-2015; Tang, Amy/L-3226-2016 OI Tang, Amy/0000-0002-5772-2878 NR 37 TC 2645 Z9 2757 U1 34 U2 188 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 1659 EP 1672 DI 10.1056/NEJMoa052306 PG 14 WC Medicine, General & Internal SC General & Internal Medicine GA 975IC UT WOS:000232653200006 PM 16236737 ER PT J AU Harris, NL Riley, LE Yawetz, S AF Harris, NL Riley, LE Yawetz, S TI Case 32-2005: A 34-year-old HIV-positive woman who desired to become pregnant - HIV infection, asymptomatic. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID HUMAN-IMMUNODEFICIENCY-VIRUS; PERINATAL TRANSMISSION; ANTIRETROVIRAL THERAPY; VERTICAL TRANSMISSION; HIV-1-INFECTED WOMEN; PROSPECTIVE COHORT; HEPATITIS-C; DELIVERY; TYPE-1; RISK C1 Massachusetts Gen Hosp, Obstet & Gynecol Serv, Boston, MA 02114 USA. Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. RP Riley, LE (reprint author), Massachusetts Gen Hosp, Obstet & Gynecol Serv, Boston, MA 02114 USA. NR 31 TC 6 Z9 6 U1 1 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 20 PY 2005 VL 353 IS 16 BP 1725 EP 1732 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 975IC UT WOS:000232653200014 ER PT J AU Ling, PD Peng, RS Nakajima, A Yu, JH Tan, J Moses, SM Yang, WH Zhao, B Kieff, E Bloch, KD Bloch, DB AF Ling, PD Peng, RS Nakajima, A Yu, JH Tan, J Moses, SM Yang, WH Zhao, B Kieff, E Bloch, KD Bloch, DB TI Mediation of Epstein-Barr virus EBNA-LP transcriptional coactivation by Sp100 SO EMBO JOURNAL LA English DT Article DE Epstein-Barr virus; gene regulation; latency; nuclear bodies; Sp100 ID ENCODED NUCLEAR ANTIGEN; ACUTE PROMYELOCYTIC LEUKEMIA; PRIMARY BILIARY-CIRRHOSIS; B-CELL LINES; LEADER PROTEIN; GENETIC-ANALYSIS; MESSENGER-RNAS; HEAT-SHOCK; PML; BODIES AB The Epstein-Barr virus (EBV) EBNA-LP protein is important for EBV-mediated B-cell immortalization and is a potent gene-specific coactivator of the viral transcriptional activator, EBNA2. The mechanism(s) by which EBNA-LP functions as a coactivator remains an important question in the biology of EBV-induced B-cell immortalization. In this study, we found that EBNA-LP interacts with the promyelocytic leukemia nuclear body (PML NB)-associated protein Sp100 and displaces Sp100 and heterochromatin protein 1 alpha (HP1 alpha) from PML NBs. Interaction between EBNA-LP and Sp100 was mediated through conserved region 3 in EBNA-LP and the PML NB targeting domain in Sp100. Overexpression of Sp100 lacking the N-terminal PML NB targeting domain, but not a mutant form of Sp100 lacking the HP1a interaction domain, was sufficient to coactivate EBNA2 in a gene-specific manner independent of EBNA-LP. These findings suggest that Sp100 is a major mediator of EBNA-LP coactivation. These studies indicate that modulation of PML NB-associated proteins may be important for establishment of latent viral infections, and also identify a convenient model system to investigate the functions of Sp100. C1 Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Massachusetts Gen Hosp, Gen Med Serv, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. Brigham & Womens Hosp, Dept Microbiol & Mol Genet, Channing Lab, Boston, MA USA. Massachusetts Gen Hosp, Gen Med Serv, Cardiovasc Res Ctr, Boston, MA 02114 USA. RP Ling, PD (reprint author), Baylor Coll Med, Dept Mol Virol & Microbiol, Mail Stop BCM-385,1 Baylor Plaza, Houston, TX 77030 USA. EM pling@bcm.tmc.edu; bloch@helix.mgh.harvard.edu FU NIDDK NIH HHS [DK-051179] NR 68 TC 56 Z9 62 U1 0 U2 0 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 3565 EP 3575 DI 10.1038/sj.emboj.7600820 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 981WJ UT WOS:000233118400005 PM 16177824 ER PT J AU Zingmond, DS McGory, ML Ko, CY AF Zingmond, DS McGory, ML Ko, CY TI Hospitalization before and after gastric bypass surgery SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID MORBIDLY OBESE-PATIENTS; BARIATRIC SURGERY; COST-EFFECTIVENESS; CARE; METAANALYSIS; OUTCOMES; IMPACT AB Context The use of Roux-en-Y gastric bypass (RYGB) has been reported to be effective in the treatment of obesity and its related comorbidities. Utilization of inpatient services after RYGB is less well understood. Objective To determine the rates and indications for inpatient hospital use before and after RYGB. Design, Setting, and Participants Retrospective study of Californians receiving RYGB in California hospitals from 1995 to 2004. Main Outcome Measure Hospitalization in the 1 to 3 years after RYGB. Results In California from 1995 to 2004, 60077 patients underwent RYGB - 11659 in 2004 alone. The rate of hospitalization in the year following RYGB was more than double the rate in the year preceding RYGB (19.3% vs 7.9%, P<.001). Furthermore, in the subset of patients (n = 24 678) with full 3-year follow-up, a mean of 8.4% were admitted a year before RYGB while 20.2% were readmitted in the year after RYGB, 18.4% in the second year after RYGB, and 14.9% in the third year after RYGB. The most common reasons for admission prior to RYGB were obesity-related problems (eg, osteoarthritis, lower extremity cellulitis), and elective operation (eg, hysterectomy), while the most common reasons for admission after RYGB were complications often thought to be procedure related, such as ventral hernia repair and gastric revision. In multivariate logistic regression models predicting 1-year readmission after RYGB, increasing Charlson Comorbidity Index score, and hospitalization in the 3-year period prior to RYGB were significantly associated with readmission within a year. Conclusions Increases in hospital use after surgery appear to be related to RYGB. Payers, clinicians, and patients must consider the not-inconsequential rate of rehospitalization after this type of surgery. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Ctr Surg Outcomes & Qual, Los Angeles, CA USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. RP Zingmond, DS (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Gen Internal Med & Hlth Serv Res, 911 Broxton Plaza, Los Angeles, CA 90095 USA. EM dzingmond@mednet.ucla.edu FU NIA NIH HHS [K08 AG023024-01A1] NR 19 TC 128 Z9 130 U1 0 U2 3 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 19 PY 2005 VL 294 IS 15 BP 1918 EP 1924 DI 10.1001/jama.294.15.1918 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 974OZ UT WOS:000232602600021 PM 16234498 ER PT J AU del Carmen, MG Rizvi, I Chang, YC Moor, ACE Oliva, E Sherwood, M Pogue, B Hasan, T AF del Carmen, MG Rizvi, I Chang, YC Moor, ACE Oliva, E Sherwood, M Pogue, B Hasan, T TI Synergism of epidermal growth factor receptor-targeted immunotherapy with photodynamic treatment of ovarian cancer in vivo SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID DISSEMINATED INTRAPERITONEAL TUMORS; PHASE-I; MONOCLONAL-ANTIBODY; BPD-MA; DEBULKING SURGERY; XENOGRAFT MODEL; THERAPY; CARCINOMA; CELLS; PHOTOFRIN AB Background. Epithelial ovarian cancer often develops resistance to standard treatments, which is a major reason for the high mortality associated with the disease. We examined the efficacy of a treatment regimen that combines immunotherapy to block the activity of epidermal growth factor receptor (EGFR), overexpression of which is associated with the development of resistant ovarian cancer, and photodynamic therapy (PDT), a mechanistically distinct photochemistrybased modality that is effective against chemo- and radioresistant ovarian tumors. Methods: We tested a combination regimen consisting of C225, a monoclonal antibody that inhibits the receptor tyrosine kinase activity of EGFR, and benzoporphyrin derivative monoacid A (BPD)-based PDT in a mouse model of human ovarian cancer. Therapeutic efficacy was evaluated in acute treatment response and survival studies that used 9-19 mice per group. Analysis of variance and Wilcoxon statistics were used to analyze the data. All statistical tests were two-sided. Results: Mice treated with PDT + C225 had the lowest mean tumor burden compared with that in the no-treatment control mice (mean percent tumor burden = 9.8%, 95% confidence interval [CI] = 2.3% to 17.3%, P <.001). Mean percent tumor burden for mice treated with C225 only or PDT only was 66.6% (95% CI = 58.7% to 74.4%, P <.001) and 38.2% (95% CI = 29.3% to 47.0%, P <.001), respectively. When compared with PDT only or C225 only, PDT + C225 produced synergistic reductions in mean tumor burden (P<.001, analysis of variance) and improvements in survival (P =.0269, Wilcoxon test). Median survival was approximately threefold greater for mice in the PDT + C225 group than for mice in the no-treatment control group (80 days versus 28 days), and more mice in the PDT + C225 group were alive at 180 days (3/9; 33% [95% CI = 7% to 70%]) than mice in the C225-only (0/12; 0% [95% CI = 0% to 22%]) or PDT-only (1/10; 10% [95% CI = 0.2% to 44%]) groups. Conclusion: A mechanistically non-overlapping combination modality consisting of receptor tyrosine kinase inhibition with C225 and BPD-PDT is well tolerated, effective, and synergistic in mice. C1 Harvard Univ, Dept Dermatol, Wellman Ctr Photomed, Massachusetts Gen Hosp,Sch Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gillette Ctr Gynecol Oncol,Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med Biostat, Boston, MA 02114 USA. Dartmouth Coll, Thayer Sch Engn, Hanover, NH 03755 USA. RP Hasan, T (reprint author), Harvard Univ, Dept Dermatol, Wellman Ctr Photomed, Massachusetts Gen Hosp,Sch Med, 40 Blossom St,Bar 314, Boston, MA 02114 USA. EM Thasan@partners.org OI Rizvi, Imran/0000-0001-9673-4700 FU NIAMS NIH HHS [R01AR40352] NR 64 TC 90 Z9 94 U1 3 U2 18 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 1516 EP 1524 DI 10.1093/jnci/dji314 PG 9 WC Oncology SC Oncology GA 979OA UT WOS:000232953500010 PM 16234565 ER PT J AU Holmes, WC Sammel, MD AF Holmes, WC Sammel, MD TI Brief communication: Physical abuse of boys and possible associations with poor adult outcomes SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID PARTNER VIOLENCE; CHILDHOOD ABUSE; SEXUAL-ABUSE; WOMEN; INSTRUMENT; VALIDITY; DISORDER AB Background: men's childhood physical abuse experiences are understudied. Objective: To obtain descriptions about men's personal childhood physical abuse histories and estimate their association with adult outcomes. Design: Population-based telephone survey. Setting: urban areas with high frequency of domestic violence against girls and women. Participants: 298 men recruited through random-digit dialing. Measurements: 6 Conflict Tactics Scale items and psychiatric, sexual, and legal history questions. Results: One hundred of 197 (51%) participants had a history of childhood physical abuse. Most (73%) participants were abused by a parent. Childhood physical abuse history was associated with depression symptoms (P = 0.003), post-traumatic stress disorder symptoms (P < 0.001), number of lifetime sexual partners (P = 0.035), legal troubles (P = 0.002), and incarceration (P = 0.007) in unadjusted analyses and with depression symptoms (P = 0.015) and post-traumatic stress disorder symptoms (P = 0.003) in adjusted analyses. Limitations: There may have been inaccurate recall of past events. Lack of exposure time data disallowed direct comparison of abuse perpetration by mothers versus fathers. Other unmeasured variables related to childhood physical abuse might better explain poor adult outcomes. Conclusions: The high frequency of childhood physical abuse histories in this population-based male sample, coupled with the high proportion of parent perpetrators and the association between childhood physical abuse and adult outcomes that are often associated with perpetration of violence, argues for more study of and clinical attentiveness to potential adult outcomes of men's own childhood physical abuse histories. C1 Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Philadelphia, PA USA. RP Holmes, WC (reprint author), Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, 733 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM holmeswc@mail.med.upenn.edu FU NIDA NIH HHS [DA015635] NR 20 TC 19 Z9 21 U1 2 U2 2 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD OCT 18 PY 2005 VL 143 IS 8 BP 581 EP 586 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 975PI UT WOS:000232674000008 PM 16230724 ER PT J AU Shusterman, S Maris, JM AF Shusterman, S Maris, JM TI Prospects for therapeutic inhibition of neuroblastoma angiogenesis SO CANCER LETTERS LA English DT Review DE neuroblastoma; angiogenesis; VEGF; MetAP2; angiogenesis inhibition ID HIGH-RISK NEUROBLASTOMA; METHIONINE AMINOPEPTIDASE-2; ANTIANGIOGENIC THERAPY; TUMOR ANGIOGENESIS; PROGNOSTIC-FACTORS; GROWTH; EXPRESSION; TNP-470; CELLS; CHEMOTHERAPY AB Despite aggressive therapy, survival for advanced stage neuroblastoma remains poor with significant long-term morbidity in disease survivors. High-risk disease features are strongly correlated with tumor vascularity, suggesting that angiogenesis inhibitors may be a useful addition to current therapeutic strategies. However, challenges include the well-known clinical heterogeneity and embryonal origins of this disease, which suggests a complex regulation of neovascularization that may be distinct from epithelial-derived carcinomas. We will review what is understood about angiogenesis-related signaling in neuroblastoma. In particular, we will present evidence that angiogenesis-related molecules are differentially expressed in primary neuroblastomas in a pattern suggesting promotion of a pro-angiogenic phenotype in high-risk tumors and an anti-angiogenic phenotype in low-risk tumors. We will also discuss a variety of vascular inhibition strategies that have been used in neuroblastoma preclinical models including specific inhibition of vascular endothelial growth factor (VEGF) and methionine aminopeptidase 2 (MetAP2). Recent observations that the combination of angiogenesis inhibitors with conventional chemotherapy provides synergy without additive toxicity, suggests the potential use of angiogenesis inhibitors as an adjunct between cycles of conventional cytotoxic therapy. Further identification of critical angiogenic signaling pathways and evaluation of specific inhibitors in preclinical neuroblastoma models should provide justification for future selection and evaluation of angiogenesis inhibitors in clinical trials for high-risk neuroblastoma patients. (C) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Cambridge, MA 02138 USA. Univ Penn, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA. Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA. RP Maris, JM (reprint author), Childrens Hosp Philadelphia, Div Oncol, ARC 902,3615 Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM maris@email.chop.edu FU NCI NIH HHS [P01-CA97323, R01-CA87847] NR 47 TC 30 Z9 32 U1 1 U2 3 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 171 EP 179 DI 10.1016/j.canlet.2005.01.049 PG 9 WC Oncology SC Oncology GA 969NN UT WOS:000232241100024 PM 15927358 ER PT J AU Carrillo-Jimenez, R Houser, SL Jaffer, FA AF Carrillo-Jimenez, R Houser, SL Jaffer, FA TI Culprit lesion atherothrombectomy during acute myocardial infarction - Extraction of an acute coronary plaque rupture SO CIRCULATION LA English DT Editorial Material C1 MGH Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol,Dept Internal Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Donald W Reynolds Cardiovasc Clin Res Ctr, Boston, MA 02115 USA. RP Jaffer, FA (reprint author), MGH Cardiol, GRB 852B,Mailstop 843,55 Fruit St, Boston, MA 02114 USA. EM fjaffer@partners.org 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 18 PY 2005 VL 112 IS 16 BP E267 EP E267 DI 10.1161/CIRCULATIONAHA.104.503656 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 974QR UT WOS:000232607000024 PM 16230488 ER PT J AU Ray, KK Cannon, CP McCabe, CH Cairns, R Tonkin, AM Sacks, FM Jackson, G Braunwald, E AF Ray, KK Cannon, CP McCabe, CH Cairns, R Tonkin, AM Sacks, FM Jackson, G Braunwald, E CA PROVE IT-TIMI 22 Investigators TI Early and late benefits of high-dose atorvastatin in patients with acute coronary syndromes SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID C-REACTIVE PROTEIN; STATIN THERAPY; HEART-DISEASE; CHOLESTEROL AB OBJECTIVES Our objective was to determine the timing of benefit with intensive statin therapy after an acute coronary syndrome (ACS) in two time windows: an early window soon after an ACS and a late window in more stable patients. BACKGROUND The Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction 22 (PROVE IT-TIMI 22) trial showed that the use of intensive statin therapy improved clinical outcomes over two years in ACS patients versus standard therapy. The relative contributions of early or late effects to the overall clinical efficacy of intensive therapy are presently unclear. METHODS A total of 4,162 patients with ACS were recruited in the PROVE IT-TIMI 22 trial. Patients were randomized to intensive statin therapy (atorvastatin, 80 mg) or standard therapy (pravastatin, 40 mg). The composite triple end point of death, MI, or rehospitalization for recurrent ACS was determined in each group at 30 days. The composite triple and primary end points were assessed in stable patients from six months to the end of study, after censoring for clinical events before six months. RESULTS The composite end point at 30 days occurred in 3.0% of patients receiving atorvastatin 80 mg versus 4.2% of patients receiving pravastatin 40 mg (hazard ratio [HR] = 0.72; 95% confidence interval [CI], 0.52 to 0.99; p = 0.046). In stable patients, atorvastatin 80 mg was associated with a composite event rate of 9.6% versus 13.1% in the pravastatin 40 mg group (HR = 0.72; 95% CI, 0.58 to 0.89; p = 0.003). CONCLUSIONS Intensive statin therapy early after ACS leads to a reduction in clinical events at 30 days, consistent with greater early pleiotropic effects. In stable patients, intensive statin therapy provides long-term reduction in clinical events when compared with standard therapy. Thus, ACS patients should be started in-hospital and continued long-term on intensive statin therapy. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. Notttingham Clin Res Grp, Nottingham, England. Monash Univ, Dept Epidemiol & Prevent Med, Melbourne, Vic 3168, Australia. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Guys Hosp, London SE1 9RT, England. RP Cannon, CP (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, TIMI Study Grp, 350 Longwood Ave,1st Floor, Boston, MA 02115 USA. EM cpcannon@partners.org NR 8 TC 176 Z9 185 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD OCT 18 PY 2005 VL 46 IS 8 BP 1405 EP 1410 DI 10.1016/j.jacc.2005.03.077 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 974GN UT WOS:000232579400001 PM 16226162 ER PT J AU Wiviott, SD Cannon, CP Morrow, DA Ray, KK Pfeffer, MA Braunwald, E AF Wiviott, SD Cannon, CP Morrow, DA Ray, KK Pfeffer, MA Braunwald, E CA PROVE IT-TIMI 22 Investigators TI Can low-density lipoprotein be too low? The safety and efficacy of achieving very low low-density lipoprotein with intensive statin therapy SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID ACUTE CORONARY SYNDROMES; RANDOMIZED CONTROLLED TRIAL; CHOLESTEROL GUIDELINES; SERUM-CHOLESTEROL; HEART-DISEASE; PRAVASTATIN; ATORVASTATIN; SIMVASTATIN; PREVENTION; MORTALITY AB OBJECTIVES This study sought to evaluate the safety and efficacy of achieving very low calculated low-density lipoprotein (LDL) levels with intensive statin therapy. BACKGROUND Intensive statin therapy reduces clinical events occurring after acute coronary syndrome (ACS) and may result in LDL levels markedly lower than guideline levels. Prior epidemiologic and preclinical studies raise concerns about the safety of very low cholesterol levels. METHODS The Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction 22 (PROVE IT-TIMI 22) study compared intensive therapy (atorvastatin, 80 mg) and moderate therapy (pravastatin, 40 mg) in patients after ACS. Patients treated with atorvastatin were divided by four-month LDL values into groups: > 100, > 80 to 100 (reference-range-meeting guidelines), > 60 to 80, > 40 to 60, and < 40 mg/dl. Baseline, clinical, and safety data were compared among groups achieving guideline recommendation levels or lower. RESULTS Among 1,825 patients with four-month LDL, 91% were at goal (< 100 mg/dl). The distribution was > 80 to 100 mg/dl (14%), > 60 to 80 mg/dl (31%), > 40 to 60 mg/dl (34%), and < 40 mg/dl (11%). Those with lower LDL levels were more often male, older, and diabetic, and had lower baseline LDL levels. They had prior statin therapy and fewer prior myocardial infarctions (MI). There were no significant differences in safety parameters, including muscle, liver, or retinal abnormalities, intracranial hemorrhage, or death, in the very low LDL groups. The < 40 mg/dl and 40 to 60 mg/dl groups had fewer major cardiac events (death, MI, stroke, recurrent ischemia, revascularization). CONCLUSIONS Compared with patients treated with an accepted LDL goal (80 to 100 mg/dl), there was no adverse effect on safety with lower achieved LDL levels, and apparent improved clinical efficacy. These data identify no intrinsic safety concern of achieving low LDL and, therefore, a strategy of intensive treatment need not be altered in patients achieving very low LDL levels. C1 Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. RP Wiviott, SD (reprint author), Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, 350 Longwood Ave,1st Floor, Boston, MA 02115 USA. EM swiviott@partners.org NR 28 TC 177 Z9 192 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD OCT 18 PY 2005 VL 46 IS 8 BP 1411 EP 1416 DI 10.1016/j.jacc.2005.04.064 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 974GN UT WOS:000232579400002 PM 16226163 ER PT J AU Ray, KK Cannon, CP Cairns, R Morrow, DA Rifai, N Kirtane, AJ McCabe, CH Skene, AM Gibson, M Ridker, PM AF Ray, KK Cannon, CP Cairns, R Morrow, DA Rifai, N Kirtane, AJ McCabe, CH Skene, AM Gibson, M Ridker, PM CA PROVE IT-TIMI 22 Investigators TI Relationship between uncontrolled risk factors and C-reactive protein levels in patients receiving standard or intensive statin therapy for acute coronary syndromes in the PROVE IT-TIMI 22 Trial SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID OBESE POSTMENOPAUSAL WOMEN; APPARENTLY HEALTHY-MEN; WEIGHT-LOSS; CARDIOVASCULAR-DISEASE; ENDOTHELIAL FUNCTION; METABOLIC SYNDROME; DIABETES-MELLITUS; ARTERY-DISEASE; INFLAMMATION; MARKERS AB OBJECTIVES This study sought to evaluate what set of factors correlate with higher or lower C-reactive protein (CRP) levels in patients receiving standard and intensive statin therapy. BACKGROUND C-reactive protein levels in blood are becoming recognized as a potential means of monitoring cardiovascular risk. Although statin therapy is known to reduce CRP levels, many patients have a high CRP level despite statin therapy. METHODS This study was a cross-sectional study of 2,885 patients from the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction 22 (PROVE IT-TIMI 22) trial, which assessed the relationship between uncontrolled cardiovascular risk factors and CRP level at four months after enrollment. RESULTS In a multivariate model, several risk factors were weakly but independently associated with higher CRP levels: age, gender (with or without hormone replacement therapy), body mass index > 25 kg/m(2), smoking, low-density lipoprotein >= 70 mg/dl, glucose > 110 mg/dl, high-density lipoprotein < 50 mg/dl, triglycerides > 150 mg/dl, and the intensity of statin therapy. A direct relationship between the number of uncontrolled risk factors present and CRP levels (p < 0.0001) was observed for both statin regimens. Despite the presence of each uncontrolled risk factor, prior randomization to intensive statin therapy was associated with a lower CRP level (p < 0.0001). Across all strata, defined by the number of uncontrolled risk factors present, CRP levels were lower among those receiving intensive statin therapy. CONCLUSIONS The use of intensive statin therapy lead to a lower CRP level independent of the presence of single or multiple cardiovascular risk factors. Even among patients receiving intensive statin therapy, a lower CRP level was observed in patients with the fewest coronary risk factors present, suggesting that control of multiple risk factors may be a means to further achieve lower CRP levels. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. Nottingham Clin Res Grp, Nottingham, England. Childrens Hosp, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Div Cardiol, Boston, MA 02215 USA. RP Cannon, CP (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, TIMI Study Grp, 350 Longwood Ave,1st Floor, Boston, MA 02115 USA. EM cpcannon@partners.org NR 36 TC 80 Z9 81 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD OCT 18 PY 2005 VL 46 IS 8 BP 1417 EP 1424 DI 10.1016/j.jacc.2005.08.024 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 974GN UT WOS:000232579400003 PM 16226164 ER PT J AU Ray, KK Cannon, CP AF Ray, KK Cannon, CP TI The potential relevance of the multiple lipid-independent (Pleiotropic) effects of statins in the management of acute coronary syndromes SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID COA REDUCTASE INHIBITORS; C-REACTIVE PROTEIN; ENDOTHELIAL PROGENITOR CELLS; VASCULAR SMOOTH-MUSCLE; MONOCYTE CHEMOATTRACTANT PROTEIN-1; TISSUE FACTOR EXPRESSION; NITRIC-OXIDE SYNTHASE; ARTERY-DISEASE; UNSTABLE ANGINA; STABLE ANGINA AB Emerging data suggest that acute presentations of coronary artery disease may involve a complex interplay between the vessel wall, inflammatory cells, and the coagulation cascade. Although a culprit thrombotic lesion may be treated effectively by antithrombotic therapy and revascularization, this will have little effect on the global processes that determine recurrent events at non-culprit sites. Thus, additional systemic treatment is required to modulate the adverse biological features that are the hallmark of acute coronary syndromes (ACS). Statins possess multiple beneficial effects that are independent of low-density-tipoprotein cholesterol (LDL-C) lowering and that have favorable effects on inflammation, the endothelium, and the coagulation cascade. In the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction 22 (PROVE IT-TIMI 22) trial, differences were seen based on achieved LDL-C that could be further discriminated by the achieved C-reactive protein level. Studies of non-vascular disease such as multiple sclerosis have shown that statins reduce inflammation, supporting the presence of lipid-independent effects of statins. This review focuses on the potential importance of these effects in the management of ACS. C1 Brigham & Womens Hosp, Dept Med, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Ray, KK (reprint author), Brigham & Womens Hosp, Dept Med, Div Cardiovasc, TIMI Study Grp, 350 Longwood Ave,1st Floor, Boston, MA 02115 USA. EM kkray@partners.org NR 71 TC 147 Z9 157 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD OCT 18 PY 2005 VL 46 IS 8 BP 1425 EP 1433 DI 10.1016/j.jacc.2005.05.086 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 974GN UT WOS:000232579400004 PM 16226165 ER PT J AU Casserly, IP Abou-Chebl, A Fathi, RB Lee, DS Saw, J Exaire, JE Kapadia, SR Bajzer, CT Yadav, JS AF Casserly, IP Abou-Chebl, A Fathi, RB Lee, DS Saw, J Exaire, JE Kapadia, SR Bajzer, CT Yadav, JS TI Slow-flow phenomenon during carotid artery intervention with embolic protection devices - Predictors and clinical outcome SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID CEREBRAL PROTECTION; HISTOPATHOLOGIC ANALYSIS; EMBOLIZATION AB OBJECTIVES The purpose of this research was to define the predictors of the "slow-reflow" phenomenon during carotid artery intervention with filter-type embolic protection devices (EPDs) and to determine its prognostic significance. BACKGROUND During carotid artery intervention using filter-type EPDs, we have observed cases in which there is angiographic evidence of a significant reduction in antegrade flow in the internal carotid artery proximal to the filter device, termed "slow-flow." The predictors of this phenomenon and its prognostic significance are unknown. METHODS Using a single-center prospective carotid intervention registry, patients with slow-flow were compared to patients with normal flow during carotid intervention with respect to clinical, procedural, and lesion characteristics, and the 30-day incidence of death and stroke. RESULTS A total of 414 patients underwent 453 carotid artery interventions using EPDs. Slow-flow occurred in 42 patients (10.1%) undergoing 42 carotid interventions (9.3%), and most commonly occurred after post-stent balloon dilatation (71.4%). Multivariate logistic regression analysis identified the following predictors of slow-flow: recent history (< 6 months) of stroke or transient ischemic attack (odds ratio [OR] 2.8, 95% confidence interval [CI] 1.4 to 5.6, p = 0.004), increased stent diameter (OR 1.4, 95% CI 1.02 to 1.94, p = 0.044), and increased patient age (OR 1.05, 95% CI 1.01 to 1.09, p = 0.025). Among patients with slow-flow, the 30-day incidence of stroke or death was 9.5% compared to 2.9% in patients with normal flow (chi-square = 4.73, p = 0.03). This difference was driven by the disparity in the 30-day incidence of stroke (9.5% vs. 1.7%). CONCLUSIONS Slow-flow during carotid intervention with EPDs is a frequent event that is associated with an excess risk of periprocedural stroke. The association of the phenomenon with clinically symptomatic carotid lesions and use of larger stent diameters C1 Cleveland Clin Fdn, Dept Cardiovasc Med, Cleveland, OH 44195 USA. Denver Vet Affairs Med Ctr, Denver, CO USA. Univ Colorado, Hlth Sci Ctr, Denver, CO 80202 USA. Vancouver Gen Hosp, Vancouver, BC, Canada. Natl Inst Hlth, Mexico City, DF, Mexico. RP Yadav, JS (reprint author), Cleveland Clin Fdn, Dept Cardiovasc Med, 9500 Euclid Ave,Desk F25, Cleveland, OH 44195 USA. EM yadavj@ccf.org NR 8 TC 59 Z9 62 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD OCT 18 PY 2005 VL 46 IS 8 BP 1466 EP 1472 DI 10.1016/j.jacc.2005.05.082 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 974GN UT WOS:000232579400008 PM 16226169 ER PT J AU Mahajan, MC Narlikar, GJ Boyapaty, G Kingston, RE Weissman, SM AF Mahajan, MC Narlikar, GJ Boyapaty, G Kingston, RE Weissman, SM TI Heterogeneous nuclear ribonucleoprotein C1/C2, MeCP1, and SWI/SNF form a chromatin remodeling complex at the beta-globin locus control region SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE NuRD/MeCP1; HS2 ID HYPERSENSITIVE SITE 2; DOMINANT CONTROL REGION; NURD REPRESSOR COMPLEX; ERYTHROID-CELLS; DEVELOPMENTAL REGULATION; GENE-TRANSCRIPTION; ENHANCER-BLOCKING; TRANSGENIC MICE; HS2 ENHANCER; IN-VITRO AB Locus control regions (LCRs) are regulatory DNA sequences that are situated many kilobases away from their cognate promoters. LCRs protect transgenes from position effect variegation and heterochromatinization and also promote copy-number dependence of the levels of transgene expression. In this work, we describe the biochemical purification of a previously undescribed LCR-associated remodeling complex (LARC) that consists of heterogeneous nuclear ribonucleoprotein C1/C2, nucleosome remodeling SWI/ SNF, and nucleosome remodeling and deacetylating (NuRD)/ MeCP1 as a single homogeneous complex. LARC binds to the hypersensitive 2 (HS2)-Maf recognition element (MARE) DNA in a sequence-specific manner and remodels nucleosomes. Heterogeneous nuclear ribonucleoprotein C1/C2, previously known as a general RNA binding protein, provides a sequence-specific DNA recognition element for LARC, and the LARC DNA-recognition sequence is essential for the enhancement of transcription by HS2. Independently of the initiation of transcription, LARC becomes associated with beta-like globin promoters. C1 Yale Univ, Sch Med, Dept Genet, Anlyan Ctr, New Haven, CT 06511 USA. Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Weissman, SM (reprint author), Yale Univ, Sch Med, Dept Genet, Anlyan Ctr, 333 Cedar St, New Haven, CT 06510 USA. EM sherman.weissman@yale.edu FU NHLBI NIH HHS [N01HV28186, N01-HV-28186, IP01HL63357-06, P01 HL063357]; NIGMS NIH HHS [R01 GM048405, R37 GM048405, GM048405] NR 44 TC 38 Z9 40 U1 1 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 15012 EP 15017 DI 10.1073/pnas.0507596102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 977NZ UT WOS:000232811800015 PM 16217013 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 Laird, JR Biamino, G Jaff, MR McNamara, T AF Laird, JR Biamino, G Jaff, MR McNamara, T TI Long-term clinical follow-up of cryoplasty for femoropopliteal arterial disease: Results of the big CHILL multicenter trial SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Meeting Abstract CT 17th Annual Transcatheter Cardiovascular Therapeutics Symposium CY OCT 17-21, 2005 CL Washington, DC SP Cardiovasc Res Fdn, Columbia Univ Med Ctr C1 Washington Hosp Ctr, Washington, DC 20010 USA. Univ Leipzig, Herzzentrum, D-7010 Leipzig, Germany. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90024 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 17 PY 2005 VL 96 IS 7A SU S BP 20H EP 20H PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 976HW UT WOS:000232725200044 ER PT J AU Jaff, MR White, CJ Ciocca, R AF Jaff, MR White, CJ Ciocca, R TI Patency of carotid stents is preserved over 12 months as determined by independent duplex ultrasound oversight: The BEACH experience SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Meeting Abstract CT 17th Annual Transcatheter Cardiovascular Therapeutics Symposium CY OCT 17-21, 2005 CL Washington, DC SP Cardiovasc Res Fdn, Columbia Univ Med Ctr C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Ochsner Clin Fdn, New Orleans, LA USA. Boston Sci Corp, Natick, MA USA. RI White, Christopher/J-6686-2012 OI White, Christopher/0000-0001-8618-7539 NR 0 TC 0 Z9 0 U1 0 U2 0 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 17 PY 2005 VL 96 IS 7A SU S BP 86H EP 86H PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 976HW UT WOS:000232725200203 ER PT J AU Nadkarni, S Bouma, B Tearney, G AF Nadkarni, S Bouma, B Tearney, G TI Estimation of collagen content and fibrous cap thickness in necrotic core fibroatheromas using laser speckle imaging SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Meeting Abstract CT 17th Annual Transcatheter Cardiovascular Therapeutics Symposium CY OCT 17-21, 2005 CL Washington, DC SP Cardiovasc Res Fdn, Columbia Univ Med Ctr C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 17 PY 2005 VL 96 IS 7A SU S BP 110H EP 111H PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 976HW UT WOS:000232725200269 ER PT J AU Nadkarni, SK Pierce, M Park, H deBoer, J Houser, S Bressner, J Bouma, B Tearney, G AF Nadkarni, SK Pierce, M Park, H deBoer, J Houser, S Bressner, J Bouma, B Tearney, G TI Analysis of collagen birefringence in atherosclerotic plaques using polarization sensitive optical coherence tomography SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Meeting Abstract CT 17th Annual Transcatheter Cardiovascular Therapeutics Symposium CY OCT 17-21, 2005 CL Washington, DC SP Cardiovasc Res Fdn, Columbia Univ Med Ctr C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA USA. NR 0 TC 2 Z9 2 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 17 PY 2005 VL 96 IS 7A SU S BP 111H EP 111H PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 976HW UT WOS:000232725200271 ER PT J AU Jaff, MR Whitlow, P Roubin, G Iyer, S Dave, R Diethrich, EB Myla, S Schwarten, D Roberts, T AF Jaff, MR Whitlow, P Roubin, G Iyer, S Dave, R Diethrich, EB Myla, S Schwarten, D Roberts, T TI Durability of carotid artery stent patency is demonstrated by duplex ultrasonography: 12-month results from the SECuRITY trials SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Meeting Abstract CT 17th Annual Transcatheter Cardiovascular Therapeutics Symposium CY OCT 17-21, 2005 CL Washington, DC SP Cardiovasc Res Fdn, Columbia Univ Med Ctr C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Lenox Hill Hosp, New York, NY 10021 USA. Harrisburg Hosp, Harrisburg, PA USA. Arizona Heart Inst, Phoenix, AZ USA. Hoag Mem Hosp, Newport Beach, CA USA. Abbott Vasc Devices, Redwood City, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 17 PY 2005 VL 96 IS 7A SU S BP 147H EP 148H PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 976HW UT WOS:000232725200371 ER PT J AU Ebrahimi, R Shah, AP Wadhani, N Saleh, JR Toggart, E AF Ebrahimi, R Shah, AP Wadhani, N Saleh, JR Toggart, E TI Statin administration prior to percutaneous coronary interventions reduces adverse cardiovascular events - A meta-analysis SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Meeting Abstract CT 17th Annual Transcatheter Cardiovascular Therapeutics Symposium CY OCT 17-21, 2005 CL Washington, DC SP Cardiovasc Res Fdn, Columbia Univ Med Ctr C1 Univ Calif Los Angeles, Sch Med, W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 17 PY 2005 VL 96 IS 7A SU S BP 155H EP 156H PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 976HW UT WOS:000232725200391 ER PT J AU Levin, WP Kooy, H Loeffler, JS DeLaney, TF AF Levin, WP Kooy, H Loeffler, JS DeLaney, TF TI Proton beam therapy SO BRITISH JOURNAL OF CANCER LA English DT Review DE radiotherapy; protein beam ID CARBON ION RADIOTHERAPY; VOLUME HISTOGRAM ANALYSIS; RADIATION-THERAPY; PROSTATE-CANCER; PHOTON RADIOTHERAPY; SKULL BASE; X-RAY; 70 GY; TUMORS; MEDULLOBLASTOMA AB Conventional radiation therapy directs photons (X-rays) and electrons at tumours with the intent of eradicating the neoplastic tissue while preserving adjacent normal tissue. Radiation-induced damage to healthy tissue and second malignancies are always a concern, however, when administering radiation. Proton beam radiotherapy, one form of charged particle therapy, allows for excellent dose distributions, with the added benefit of no exit dose. These characteristics make this form of radiotherapy an excellent choice for the treatment of tumours located next to critical structures such as the spinal cord, eyes, and brain, as well as for paediatric malignancies. C1 Massachusetts Gen Hosp NE, Proton Therapy Ctr, Boston, MA 02114 USA. RP DeLaney, TF (reprint author), Massachusetts Gen Hosp NE, Proton Therapy Ctr, Boston, MA 02114 USA. EM TDELANEY@PARTNERS.ORG NR 35 TC 96 Z9 97 U1 6 U2 23 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 849 EP 854 DI 10.1038/sj.bjc.6602754 PG 6 WC Oncology SC Oncology GA 972ZL UT WOS:000232492400001 PM 16189526 ER PT J AU Song, YQ Manson, JE Cook, NR Albert, CM Buring, JE Liu, SM AF Song, YQ Manson, JE Cook, NR Albert, CM Buring, JE Liu, SM TI Dietary magnesium intake and risk of cardiovascular disease among women SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; CORONARY-HEART-DISEASE; FOCAL CEREBRAL-ISCHEMIA; INTRAVENOUS MAGNESIUM; RANDOMIZED TRIALS; US WOMEN; STROKE; SULFATE; HYPERTENSION; POTASSIUM AB This study assessed the hypothesis that greater magnesium intake is associated with reduced risk for cardiovascular disease (CVD), including myocardial infarction (MI) and stroke, in a large prospective cohort of women. In 1993, a semi-quantitative food. frequency questionnaire was used to assess magnesium intake in 39,876 female health professionals aged 39 to 89 years who had no history of CVD or cancer. During a median of 10 years of follow-up, 1,037 incident cases of CVD were identified, including 280 nonfatal MIs and 368 strokes. After adjustment for age and randomized treatment status, magnesium intake was not significantly associated with risk for incident CVD. Comparing the highest, quintile of magnesium intake (median 433 mg/day) with the lowest quintile (median 255 mg/day), the relative risks were 0.87 (95%.confidence interval [CI] 0.72 to 1.05, p for trend = 0.24) for total CVD, 0.88 (95% CI 0.70 to 1.12, p for trend = 0.34) for coronary heart disease (CHD), 1.03 (95% CI 0.72 to 1.49, p for trend = 0.96) for nonfatal MI, 1.11 (95% CI 0.61 to 2.00, p for trend = 0.95) for CVD death, and 0.87 (95% Cl 0.64 to 1.18, p for trend = 0.55) for total stroke. Additional adjustment for other CVD risk factors did not materially change the observed null associations. In conclusion, the results do not support the hypothesis that magnesium intake reduces the development of CHD, although a modest inverse association with stroke cannot be ruled out. (c) 2005 Elsevier Inc. All rights reserved. C1 Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. RP Song, YQ (reprint author), Brigham & Womens Hosp, Dept Med, Div Prevent Med, 75 Francis St, Boston, MA 02115 USA. EM ysong@hsph.harvard.edu RI Liu, Simin/I-3689-2014 OI Liu, Simin/0000-0003-2098-3844 FU NCI NIH HHS [CA-47988]; NHLBI NIH HHS [HL-43851]; NIDDK NIH HHS [DK66401] NR 29 TC 46 Z9 47 U1 0 U2 5 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD OCT 15 PY 2005 VL 96 IS 8 BP 1135 EP 1141 DI 10.1016/j.amjcard.2005.06.045 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 977MZ UT WOS:000232809200019 PM 16214452 ER PT J AU Sebag, IA Morgan, JG Handschumacher, MD Marshall, JE Nesta, F Hung, J Picard, MH Levine, RA AF Sebag, IA Morgan, JG Handschumacher, MD Marshall, JE Nesta, F Hung, J Picard, MH Levine, RA TI Usefulness of three-dimensionally guided assessment of mitral stenosis using matrix-array ultrasound SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID VALVE-STENOSIS; AORTIC-STENOSIS; ORIFICE AREA; ECHOCARDIOGRAPHY; TIME; QUANTIFICATION; ACCURATE; DESIGN; SYSTEM AB Two-dimensional (2-D) planimetry is limited by the technical demands, time, and observer variability required to locate the minimal orifice area, limiting the confident clinical reporting of mitral valve area (MVA). In 27 consecutive patients, MVA was determined independently by 2 observers using the conventional 2-D method and a new 3-D-guided method. Using a matrix-array probe, the valve was visualized in a long-axis view and a cursor steered to intersect the leaflet tips and provide a perpendicular short-axis plane viewed side-by-side. Two-dimensional and 3-D-guided methods allowed planimetry in 24 patients. Consistent with better orifice localization, 3-D guidance eliminated the overestimation of internal orifice diameters in the planimetered short-axis view relative to the limiting diameter defined by the long-axis view (for 3-D guidance, 0.73 +/- 0.20 vs 0.73 +/- 0.21 cm, p = 0.98, vs 0.90 +/- 0.27 cm in the 2-D short-axis view, p < 0.01). Accordingly, mean values for the smallest orifice area by 3-D guidance were less than by 2-D imaging (1.4 +/- 0.5 vs 1.5 +/- 0.5 cm(2), p <0.01), changing the clinical severity classification in 11 of 24 patients (46%). The 2-D method also overestimated MVA relative to 3-D guidance compared with Doppler pressure halftime and (n = 6). Gorlin areas. Phantom studies verified no differences in resolution for the 2 acquisition modes. Three-dimensional guidance reduced intraobserver variability from 9.8% to 3.8% (SEE 0.14 to 0.06 cm(2), P <0.01) and 2 interobserver variability from 10.6% to 6.1% (SEE 0.15 to 0.09 cm(2) p <0.02). In conclusion, matrix-array technology provides a feasible and highly reproducible direct 3-D-guided method for measuring the limiting mitral orifice area. (c) 2005 Elsevier Inc. All. rights reserved. C1 Massachusetts Gen Hosp, Dept Med, Div Cardiol, Cardiac Ultrasond Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Sir Mortimer B Davis Jewish Hosp, Div Cardiol, Echocardiog Lab, Montreal, PQ H3T 1E2, Canada. McGill Univ, Montreal, PQ H3A 2T5, Canada. RP Levine, RA (reprint author), Massachusetts Gen Hosp, Dept Med, Div Cardiol, Cardiac Ultrasond Lab, Boston, MA 02114 USA. EM rlevine@partners.org OI Picard, Michael/0000-0002-9264-3243 NR 21 TC 30 Z9 30 U1 0 U2 0 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 1151 EP 1156 DI 10.1016/j.amjcard.2005.06.046 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 977MZ UT WOS:000232809200022 PM 16214455 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 Aujesky, D Obrosky, DS Stone, RA Auble, TE Perrier, A Cornuz, J Roy, PM Fine, MJ AF Aujesky, D Obrosky, DS Stone, RA Auble, TE Perrier, A Cornuz, J Roy, PM Fine, MJ TI Derivation and validation of a prognostic model for pulmonary embolism SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE mortality; prognosis; pulmonary embolism ID DEEP-VEIN THROMBOSIS; MOLECULAR-WEIGHT HEPARIN; OUTPATIENT TREATMENT; UNFRACTIONATED HEPARIN; VENOUS THROMBOSIS; RISK SCORE; TROPONIN-T; TOTAL HIP; OUTCOMES; HYPONATREMIA AB Rationale: An objective and simple prognostic model for patients with pulmonary embolism could be helpful in guiding initial intensity of treatment. Objectives:To develop a clinical prediction rule that accurately classifies patients with pulmonary embolism into categories of increasing risk of mortality and other adverse medical outcomes. Methods: We randomly allocated 15,531 inpatient discharges with pulmonary embolism from 186 Pennsylvania hospitals to derivation (67%) and internal validation (33%) samples. We derived our prediction rule using logistic regression with 30-day mortality as the primary outcome, and patient demographic and clinical data routinely available at presentation as potential predictor variables. We externally validated the rule in 221 inpatients with pulmonary embolism from Switzerland and France. Measurements: We compared mortality and nonfatal adverse medical outcomes across the derivation and two validation samples. Main Results: The prediction rule is based on 11 simple patient characteristics that were independently associated with mortality and stratifies patients with pulmonary embolism into five severity classes, with 30-day mortality rates of 0-1.6% in class I, 1.7-3.5% in class II, 3.2-7.1% in class III, 4.0-11.4% in class IV, and 10.0-24.5% in class V across the derivation and validation samples. Inpatient death and nonfatal complications were <= 1.1% among patients in class I and <= 1.9% among patients in class II. Conclusions: Our rule accurately classifies patients with pulmonary embolism into classes of increasing risk of mortality and other adverse medical outcomes. Further validation of the rule is important before its implementation as a decision aid to guide the initial management of patients with pulmonary embolism. C1 Univ Lausanne, Div Gen Internal Med, Clin Epidemiol Ctr, CH-1015 Lausanne, Switzerland. Univ Lausanne, Outpatient Clin, CH-1015 Lausanne, Switzerland. Univ Geneva, Dept Internal Med, Div Gen Internal Med, CH-1211 Geneva, Switzerland. Univ Pittsburgh, Div Gen Internal Med, Dept Med, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Emergency Med, Pittsburgh, PA 15260 USA. VA Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. Univ Angers, Dept Emergency Med, Angers, France. RP Aujesky, D (reprint author), CHU Vaudois, Serv Med Interne, BH10-622, CH-1011 Lausanne, Switzerland. EM drahomir.aujesky@chuv.ch RI Perrier, Arnaud/M-2263-2014 FU NHLBI NIH HHS [1 R21 HL075521-01A1]; NIAID NIH HHS [K24 AI001769] NR 35 TC 326 Z9 336 U1 0 U2 7 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 1041 EP 1046 DI 10.1164/rccm.200506-862OC PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 975OM UT WOS:000232671800018 PM 16020800 ER PT J AU Kozel, FA Johnson, KA Mu, QW Grenesko, EL Laken, SJ George, MS AF Kozel, FA Johnson, KA Mu, QW Grenesko, EL Laken, SJ George, MS TI Detecting deception using functional magnetic resonance imaging SO BIOLOGICAL PSYCHIATRY LA English DT Article DE deception; lie; detection; fMRI; BOLD; individual ID LIE DETECTION; INTERFERENCE TASK; COUNTERMEASURES; POLYGRAPH; CONFLICT; STROOP; CORTEX; TESTS; FMRI AB Background: The ability to accurately detect deception is presently very limited. Detecting deception might be more accurately achieved by measuring the brain correlates of lying in an individual. In addition, a method to investigate the neurocircuitry of deception might provide a unique opportunity to test the neurocircuitry of persons in whom deception is a prominent component (i.e., conduct disorder. antisocial personality disorder, etc,). Methods: In this study. we used functional magnetic resonance imaging (fMRI) to show that specific regions were reproducibly activated when subjects deceived. Subjects participated in a mock crime stealing either a ring or a watch. While undergoing an fMRI, the subjects denied taking either object, thus telling the truth with some responses, and lying with others. A Model-Building Group (MBG, n = 30) was used to develop the analysis methods, and the methods were subsequently applied to an independent Model-Testing Group (MTG, n = 31). Results: Me were able to correctly, differentiate truthful from deceptive responses, correctly identifying The object stolen, for 93% of the sujects in the MBG and 90% of the subjects in the MTG. Conclusions: This is the first study to use fMRI to detect deception at the individual level. Further work is required to determine bow well this technology will work in different settings and populations. C1 Med Univ S Carolina, Ctr Adv Imaging Res, Charleston, SC 29425 USA. Med Univ S Carolina, Brain Stimulat Lab, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. Ralph H Johnson VA Hosp, Charleston, SC USA. Cephos Corp, Pepperell, MA USA. RP Kozel, FA (reprint author), Univ Texas, SW Med Ctr, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM andrew.kozel@utsouthwestern.edu RI Kozel, Frank/I-5366-2012 NR 31 TC 146 Z9 153 U1 7 U2 37 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 605 EP 613 DI 10.1016/j.biopsych.2005.07.040 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 981NU UT WOS:000233096100002 PM 16185668 ER PT J AU Hazlett, EA New, AS Newmark, R Haznedar, MM Lo, JN Speiser, LJ Chen, AD Mitropoulou, V Minzenberg, M Siever, LJ Buchsbaum, MS AF Hazlett, EA New, AS Newmark, R Haznedar, MM Lo, JN Speiser, LJ Chen, AD Mitropoulou, V Minzenberg, M Siever, LJ Buchsbaum, MS TI Reduced anterior and posterior cingulate gray matter in borderline personality disorder SO BIOLOGICAL PSYCHIATRY LA English DT Article DE borderline personality disorder; schizotypal personality disorder; magnetic resonance imaging; cingulate; gray matter volume; white matter volume ID POSITRON-EMISSION-TOMOGRAPHY; MAGNETIC-RESONANCE; GLUCOSE-METABOLISM; BRAIN ABNORMALITIES; CHILDHOOD ABUSE; FEMALE-PATIENTS; BRODMANN AREAS; 1ST EPISODE; CORTEX; SCHIZOPHRENIA AB Background: Structural abnormalities in prefrontal and cingulate gyrus regions-important in affective processing, impulse control and cognition may contribute to the psychopathology of borderline personality disorder (BPD). Previous MRI studies examining volume have reported that compared with healthy controls, BPD patients have decreases in tight anterior cingulate, no differences in dorsolateral prefrontal cortex, and mixed findings for prefrontal cortex. We extended this investigation by examining gray and white matter volume of frontal and cingulate gyrus Brodmann areas (BAs) in a large group of patients and healthy controls. Methods. MRI scans were acquired in 50 BPD patients (n = 13 with comorbid diagnosis of BPD and Schizotypal Personality Disorder (SPD) and n = 3 7 without SPD) and 50 healthy controls, and gray/white matter volume in cingulate gyrus and frontal lobe BAs were assessed. Normal BPD and BPD subgroup comparisons were conducted. Results. Compared with controls, BPD patients showed reduced gray matter volume in BA 24 and 31 of the cingulate. BPD patients without comorbid SPD bad isolated gray matter volume loss in BA 24, but were spared for BA 31 in contrast to BPD patients with SPD. There were no group differences in whole cingulate or frontal lobe volume. Conclusions. The finding of more pervasive cingulate shrinkage in the patients with BPD and SPD comorbidity resembles recent observations with the same methods in patients with schizophrenia. The pattern of reduced anterior and posterior cingulate gray matter volume in BPD patients, particularly those comorbid for SPD is consistent with the affective and attentional deficits observed in these personality disorders. C1 Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. Bronx Vet Affairs Med Ctr, New York, NY USA. RP Hazlett, EA (reprint author), Mt Sinai Sch Med, Dept Psychiat, Box 1505, New York, NY 10029 USA. EM erin.hazlett@mssm.edu FU NCRR NIH HHS [M01 RR 00071]; NIMH NIH HHS [MH 56489, MH 40071, MH 56606] NR 67 TC 106 Z9 109 U1 3 U2 7 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 614 EP 623 DI 10.1016/j.biopsych.2005.04.029 PG 10 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 981NU UT WOS:000233096100003 PM 15993861 ER PT J AU Lutskiy, MI Beardsley, DS Rosen, FS Remold-O'Donnell, E AF Lutskiy, MI Beardsley, DS Rosen, FS Remold-O'Donnell, E TI Mosaicism of NK cells in a patient with Wiskott-Aldrich syndrome SO BLOOD LA English DT Article ID NATURAL-KILLER-CELLS; IN-VIVO REVERSION; DENDRITIC CELLS; SYNDROME PROTEIN; WASP; ACTIVATION; MUTATIONS; CYTOTOXICITY; EXPRESSION; RECEPTORS AB Rare cases of somatic mosaicism resulting from reversion of inherited mutations can lead to the attenuation of blood-cell disorders, including Wiskott-Aldrich syndrome (WAS). The impact of the revertant hematopoietic stem or progenitor cells, particularly their representation in blood-cell populations, is of interest because it predicts the outcome of gene therapy. Here we report an 8-year-old patient with WAS caused by a single nucleotide insertion in the WASP gene that abrogates protein expression. The patient nonetheless had mild disease. We found reversion of the mutation in a fraction of patient lymphocytes. Forty percent of natural killer (NK) cells expressed Wiskott-Aldrich syndrome protein (WASP), and NK cells contained both mutated and revertant (normal) sequences. WASP was not expressed in patient T or B cells; T cells contained only the mutated sequence. The selective advantage of WASP(+) NK cells was also demonstrated for carrier females. The enrichment of WASP(+)-revertant NK cells indicates that WASP provides a selective advantage in this lineage and predicts the success of gene therapy for reconstituting the NK-cell compartment. The importance of reconstituting the NK-cell lineage is discussed. C1 CBR Inst Biomed Res Inc, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06510 USA. RP Remold-O'Donnell, E (reprint author), CBR Inst Biomed Res Inc, Boston, MA 02115 USA. EM remold@cbr.med.harvard.edu FU NHLBI NIH HHS [P01 HL059561, HL59561]; NIAID NIH HHS [AI39574, R01 AI039574] NR 21 TC 23 Z9 24 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD OCT 15 PY 2005 VL 106 IS 8 BP 2815 EP 2817 DI 10.1182/blood-2004-12-4724 PG 3 WC Hematology SC Hematology GA 972PP UT WOS:000232466000039 PM 15985539 ER PT J AU Stegmaier, K Corsello, SM Ross, KN Wong, JS DeAngelo, DJ Golub, TR AF Stegmaier, K Corsello, SM Ross, KN Wong, JS DeAngelo, DJ Golub, TR TI Gefitinib induces myeloid differentiation of acute myeloid leukemia SO BLOOD LA English DT Article ID GROWTH-FACTOR RECEPTOR; TYROSINE KINASE INHIBITOR; ACUTE PROMYELOCYTIC LEUKEMIA; TRANS-RETINOIC ACID; GRANULOCYTIC DIFFERENTIATION; MYELOGENOUS LEUKEMIA; ZD1839 IRESSA; HL-60 CELLS; IN-VIVO; CANCER AB Cure rates for patients with acute myeloid leukemia (AML) remain low despite ever-increasing dose intensity of cytotoxic therapy. In an effort to identify novel approaches to AML therapy, we recently reported a new method of chemical screening based on the modulation of a gene expression signature of interest. We applied this approach to the discovery of AML-differentiation-promoting compounds. Among the compounds inducing neutrophilic differentiation was DAPH1 (4,5-dianilinophthalimide), previously reported to inhibit epidermal growth factor receptor (EGFR) kinase activity. Here we report that the Food and Drug Administration (FDA)-approved EGFR inhibitor gefitinib similarly promotes the differentiation of AML cell lines and primary patient-derived AML blasts in vitro. Gefitinib induced differentiation based on morphologic assessment, nitro-blue tetrazolium reduction, cell-surface markers, genome-wide patterns of gene expression, and inhibition of proliferation at clinically achievable doses. Importantly, EGFR expression was not detected in AML cells, indicating that gefitinib functions through a previously unrecognized EGFR-independent mechanism. These studies indicate that clinical trials testing the efficacy of gefitinib in patients with AML are warranted. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Sch Med, Boston, MA 02115 USA. MIT, Eli & Edythe L Broad Inst, Cambridge, MA 02139 USA. Harvard Univ, Cambridge, MA 02138 USA. Howard Hughes Med Inst, Chevy Chase, MD USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Golub, TR (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, D640,44 Binney St, Boston, MA 02115 USA. EM golub@broad.mit.edu FU NCI NIH HHS [5K08 CA098444-03] NR 29 TC 90 Z9 94 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 15 PY 2005 VL 106 IS 8 BP 2841 EP 2848 DI 10.1182/blood-2005-02-0488 PG 8 WC Hematology SC Hematology GA 972PP UT WOS:000232466000043 PM 15998836 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 Gunshin, H Starr, CN DiRenzo, C Fleming, MD Jin, J Greer, EL Sellers, VM Galica, SM Andrews, NC AF Gunshin, H Starr, CN DiRenzo, C Fleming, MD Jin, J Greer, EL Sellers, VM Galica, SM Andrews, NC TI Cybrd1 (duodenal cytochrome b) is not necessary for dietary iron absorption in mice SO BLOOD LA English DT Article ID FERRIC REDUCTASE; EXPRESSION; TRANSPORTER; METABOLISM; HEPCIDIN; CELLS; LIVER AB Mammalian northeme iron absorption requires reduction of dietary iron for uptake by the divalent metal ion transport system in the intestine. This was thought to be mediated by duodenal cytochrome b (Cybrd1), a ferric reductase enzyme resident on the luminal surface of intestinal absorptive cells. To test its importance in vivo, we inactivated the murine Cybrd1 gene and assessed tissue iron stores in Cybrd1-null mice. We found that loss of Cybrd1 had little or no impact on body iron stores, even in the setting of iron deficiency. We conclude that other mechanisms must be available for the reduction of dietary iron. C1 Harvard Univ, Sch Med, Childrens Hosp,Dana Farber Canc Inst, Karp Family Res Labs RM 8 125, Boston, MA 02115 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. RP Andrews, NC (reprint author), Harvard Univ, Sch Med, Childrens Hosp,Dana Farber Canc Inst, Karp Family Res Labs RM 8 125, Boston, MA 02115 USA. EM nancy-andrews@hms.harvard.edu OI Greer, Eric/0000-0002-7501-7371; Andrews, Nancy/0000-0003-0243-4462 FU NICHD NIH HHS [P30 HD018655]; NIDDK NIH HHS [K01 DK02804, R01 DK 066373, R01 DK053813, R01 DK053813-10, R01 DK062474, R01 DK066373, R01 DK53813] NR 18 TC 101 Z9 107 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD OCT 15 PY 2005 VL 106 IS 8 BP 2879 EP 2883 DI 10.1182/blood-2005-02-0716 PG 5 WC Hematology SC Hematology GA 972PP UT WOS:000232466000049 PM 15961514 ER PT J AU Zorn, E Kim, HT Lee, SJ Floyd, BH Litsa, D Arumugarajah, S Bellucci, R Alyea, EP Antin, JH Soiffer, RJ Ritz, J AF Zorn, E Kim, HT Lee, SJ Floyd, BH Litsa, D Arumugarajah, S Bellucci, R Alyea, EP Antin, JH Soiffer, RJ Ritz, J TI Reduced frequency of FOXP3(+) CD4(+)CD25(+) regulatory T cells in patients with chronic graft-versus-host disease SO BLOOD LA English DT Article ID BONE-MARROW-TRANSPLANTATION; TRANSCRIPTION FACTOR FOXP3; IMMUNE RECONSTITUTION; INCREASED NUMBERS; PERIPHERAL-BLOOD; LEUKEMIA; LYMPHOCYTES; ACTIVATION; TOLERANCE; INFUSION AB Chronic graft-versus-host disease (cGVHD) is a major complication of allogeneic hematopoietic stem cell transplantation but the immune mechanisms leading to the diverse clinical manifestations of cGVHD remain unknown. In this study, we examined regulatory T cells (Tregs) in 57 transplant recipients (30 with cGVHD and 27 without active cGVHD) and 26 healthy donors. Phenotypic studies demonstrated decreased frequency of CD4(+)CD25(+) T cells in patients with cGVHD compared with patients without cGVHD (P <.001) and healthy individuals (P <.001). Gene expression of Treg transcription factor FOXP3 was reduced in cGVHD patients compared with patients without cGVHD (P =.009) or healthy donors (P =.01). T-cell receptor excision circle (TREC) assays for the evaluation of thymus activity revealed fewer TRECs in both transplant groups compared with healthy donors (P <.001 and P =.02, respectively) although no difference was observed between patients with or without cGVHD (P =.13). When tested in functional assays, Tregs from both patient cohorts and healthy individuals mediated equivalent levels of suppression. Collectively, these studies indicate that patients with active cGVHD have reduced frequencies of Tregs but the function of these cells remains normal. These findings support the development of new strategies to increase the number of Tregs following allogeneic hematopoietic stem cell transplantation to prevent or correct cGVHD. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Ritz, J (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM jerome_ritz@dfci.harvard.edu FU NHLBI NIH HHS [HL70149]; NIAID NIH HHS [AI29530] NR 39 TC 243 Z9 258 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 2903 EP 2911 DI 10.1182/blood-2005-03-1257 PG 9 WC Hematology SC Hematology GA 972PP UT WOS:000232466000053 PM 15972448 ER PT J AU Peppercorn, J Herndon, J Kornblith, AB Peters, W Ahles, T Vredenburgh, J Schwartz, G Shpall, E Hurd, DD Holland, J Winer, E AF Peppercorn, J Herndon, J Kornblith, AB Peters, W Ahles, T Vredenburgh, J Schwartz, G Shpall, E Hurd, DD Holland, J Winer, E CA CALGB SWOG TI Quality of life among patients with stage II and III breast carcinoma randomized to receive high-dose chemotherapy with autologous bone marrow support or intermediate-dose chemotherapy - Results from cancer and leukemia group B 9066 SO CANCER LA English DT Article DE assessment scales; autologous stem cell support; breast carcinoma; high-dose chemotherapy; quality of life ID STEM-CELL TRANSPLANTATION; ADJUVANT TREATMENT; PSYCHOLOGICAL DISTRESS; POSITIVE NODES; THERAPY; TRIAL; CYCLOPHOSPHAMIDE; FLUOROURACIL; EPIRUBICIN; VALIDATION AB BACKGROUND. The objective of this study was to compare the quality of life (QOL) after treatment among patients who had breast carcinoma with multiple positive lymph nodes. The patients were randomized to receive either high-dose chemotherapy with autologous stem cell support (HDC) or intermediate-dose chemotherapy (IDC) in the adjuvant setting. METHODS. Two hundred forty-six patients with AJCC Stage IIA, IIB, or IIIA breast carcinoma who had >= 10 positive lymph nodes and who were participants in Cancer and Leukemia Group B (CALGB) 9082 were enrolled in this companion study, CALGB 9066. Patients were randomized to receive either high-dose cyclophosphamide, carmustine, and cisplatin (CPA/cDDP/BCNU) and autologous bone marrow transplantation (the HDC arm) or intermediate-dose CPA/cDDP/BCNU as consolidation to adjuvant chemotherapy (the IDC arm). QOL was assessed at baseline and at 3 months, 12 months, 24 months, and 36 months using the Functional Living Index-Cancer (FLIC), the Psychosocial Adjustment to Illness Scale (PAIS)-Self Report, and the McCorkle Symptom Distress Scale (SDS). RESULTS. At the 3-month assessment, patients in the HDC arm demonstrated significant worsening of QOL compared with the IDC arm in terms of their physical well being (FLIC, P = 0.023), social functioning (FLIC, P = 0.026; PAIS, P < 0.0001), symptom distress (SDS, P = 0.0002), and total QOL scores (FLIC, P = 0.042). At 12 months, the differences in QOL scores between the HDC arm and the IDC arm had resolved. CONCLUSIONS. Patients who received more intensive adjuvant therapy experienced transient declines in QOL. By 12 months after therapy, QOL was comparable between the 2 arms, regardless of therapy intensity, and many QOL areas were improved from baseline. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. Ctr Stat, Canc & Leukemia Grp B, Durham, NC USA. Adherex Technol Inc, Durham, NC USA. Dartmouth Coll Sch Med, Norris Cotton Canc Ctr, Dept Psychiat, Lebanon, NH USA. Duke Univ, Med Ctr, Duke Comprehens Canc Ctr, Dept Med, Durham, NC 27710 USA. Dartmouth Coll Sch Med, Norris Cotton Canc Ctr, Dept Med, Lebanon, NH USA. Univ Texas, MD Anderson Canc Ctr, Dept Blood & Marrow Transplantat, Houston, TX 77030 USA. Wake Forest Univ, Sch Med, Dept Hematol Oncol, Winston Salem, NC 27109 USA. Mem Sloan Kettering Canc Ctr, Dept Psychiat & Behav Sci, New York, NY 10021 USA. RP Winer, E (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM eric-winer@dfci.harvard.edu FU NCI NIH HHS [CA07968, CA08025, CA77440, CA31809, CA14028, CA37135, CA04457, CA31946, CA32291, CA60138, CA04326, CA16450, CA77651, CA41287, CA47642, CA47559, CA47545, CA11789, CA02599, CA47577, CA31983, CA03927, CA21060, CA35279, CA42777, CA33601] NR 32 TC 19 Z9 19 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 15 PY 2005 VL 104 IS 8 BP 1580 EP 1589 DI 10.1002/cncr.21363 PG 10 WC Oncology SC Oncology GA 973FM UT WOS:000232508300005 PM 16118805 ER PT J AU Lee, H McGovern, K Finkelstein, JS Smith, MR AF Lee, H McGovern, K Finkelstein, JS Smith, MR TI Changes in bone mineral density and body composition during initial and long-term gonadotropin-releasing hormone agonist treatment for prostate carcinoma SO CANCER LA English DT Article DE prostatatic neoplasms; gonadotropin-releasing hormone agonist; osteoporosis; bone mineral density; body composition ID ANDROGEN-DEPRIVATION THERAPY; RANDOMIZED CONTROLLED-TRIAL; QUALITY-OF-LIFE; POSTMENOPAUSAL OSTEOPOROSIS; RANCHO BERNARDO; SEX STEROIDS; OLDER MEN; CANCER; WOMEN; ESTROGENS AB BACKGROUND. Initial treatment with a gonadotropin-releasing hormone (GnRH) agonist increases fat mass, decreases lean body mass, and decreases bone mineral density (BMD) in men with prostate carcinoma. To the authors' knowledge, little is known regarding either the long-term effects of treatment or predictors of treatment-related changes in BMD and body composition. METHODS. The authors analyzed prospective 12-month data from 65 men during initial and long-term GnRH agonist treatment for prostate carcinoma. Relationships between baseline characteristics (age, treatment duration, body mass index,. and baseline values for outcome of interest) and changes in lean mass, fat mass, and BMD were assessed using univariate and multivariate regression models. RESULTS. Mean BMD of total hip decreased by 1.9 +/- 2.7%, lean body mass decreased by 2.0 +/- 3.3%, and fat mass increased by 6.6 +/- 9.4% at 12 months (P < 0.001 for each comparison). Twenty-three men (35%) had received treatment with a GnRH agonist before study entry, and the mean (+/- standard deviation) duration of previous treatment was 35 +/- 41 months. Longer duration of previous GnRH agonist treatment was found to independently predict less fat accumulation and less loss of lean body mass in multivariate models. In contrast, the duration of GnRH agonist treatment did not significantly predict changes in BMD. Other covariates did not appear to predict changes in body composition or BMD consistently. CONCLUSIONS. The results of the current study showed that fat mass increased and lean body mass decreased mostly during initial GnRH agonist therapy whereas BMD decreased steadily during initial and long-term treatment. C1 Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. RP Smith, MR (reprint author), Massachusetts Gen Hosp, Div Hematol & Oncol, Cox 640,100 Blossom St, Boston, MA 02114 USA. EM smith.matthew@mgh.harvard.edu NR 24 TC 84 Z9 86 U1 0 U2 1 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 1633 EP 1637 DI 10.1002/cncr.21381 PG 5 WC Oncology SC Oncology GA 973FM UT WOS:000232508300011 PM 16116596 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 Nunes, F Shen, YP Niida, Y Beauchamp, R Stemmer-Rachamimov, AO Ramesh, V Gusella, J MacCollin, M AF Nunes, F Shen, YP Niida, Y Beauchamp, R Stemmer-Rachamimov, AO Ramesh, V Gusella, J MacCollin, M TI Inactivation patterns of NF2 and DAL-1/4.1B (EPB41L3) in sporadic meningioma SO CANCER GENETICS AND CYTOGENETICS LA English DT Article; Proceedings Paper CT 53rd Annual Meeting of the American-Society-of-Human-Genetics CY NOV 04-08, 2003 CL LOS ANGELES, CA SP Amer Soc Human Genet ID COMPARATIVE GENOMIC HYBRIDIZATION; TUMOR-SUPPRESSOR GENE; ANAPLASTIC MENINGIOMAS; MOLECULAR-BASIS; HETEROZYGOSITY; CLASSIFICATION; MUTATION; LOSSES; 22Q AB The molecular basis of tumorigenesis and tumor progression in meningiomas is not fully understood. The neurofibromatosis 2 (NF2) locus is inactivated in 50-60% of sporadic meningiomas, but the genetic basis of sporadic meningiomas not inactivated at the NF2 locus remains unclear. Specifically, there is conflicting data regarding the role of the tumor suppressor gene DAL-1/4.1B. Using microsatellite markers, we studied 63 sporadic meningiomas to determine loss of heterozygosity (LOH) at the NF2 and DAL-1/1.B loci. Array comparative genomic hybridization analysis of 52 of these tumors was performed to determine copy number changes on chromosomes 18 and 22. Forty-one of 62 informative tumors showed LOH at the NF2 locus (66%) while only 12 of 62 informative tumors (19%) showed LOH of DAL-1/4.1B. Eleven of 12 (92%) tumors with DAL-1/4.1B LOH also had NF2 LOH. Monosomy or large deletions of chromosomes 18 and 22 were the main mechanism for LOH in these tumors. These studies implicate the DAL-1/4.1B locus in sporadic meningiomas less commonly than reported previously, and suggest that it is a progression rather than an initiation locus. Furthermore, we found the majority of meningiomas developed monosomy rather than isodisomy at the NF2 and DAL-114.1B loci as the mechanism for LOH. (c) 2005 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Ctr Human Genet Res, Mol Neurogenet Unit, Charlestown, MA USA. Kanazawa Univ, Grad Sch Med Sci, Dept Pediat, Kanazawa, Ishikawa, Japan. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Mol Neurooncol Lab, Boston, MA USA. Massachusetts Gen Hosp, Pathol Lab, Boston, MA USA. Massachusetts Gen Hosp, Canc Ctr, Boston, MA USA. RP Nunes, F (reprint author), Massachusetts Gen Hosp, Dept Neurol, Bldg 149,13th St, Charlestown, MA 02129 USA. EM fnunes@partners.org FU NINDS NIH HHS [NS24279] NR 23 TC 39 Z9 41 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0165-4608 J9 CANCER GENET CYTOGEN JI Cancer Genet. Cytogenet. PD OCT 15 PY 2005 VL 162 IS 2 BP 135 EP 139 DI 10.1016/j.cancergencyto.2005.04.003 PG 5 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 984HF UT WOS:000233292800007 PM 16213361 ER PT J AU Kim, YR Yudina, A Figueiredo, J Reichardt, W Hu-Lowe, D Petrovsky, A Kang, HW Torres, D Mahmood, U Weissleder, R Bogdanov, AA AF Kim, YR Yudina, A Figueiredo, J Reichardt, W Hu-Lowe, D Petrovsky, A Kang, HW Torres, D Mahmood, U Weissleder, R Bogdanov, AA TI Detection of early antiangiogenic effects in human colon adenocarcinoma xenografts: In vivo changes of tumor blood volume in response to experimental VEGFR tyrosine kinase inhibitor SO CANCER RESEARCH LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; INDUCED ANGIOGENESIS; VASCULAR VOLUME; CONTRAST AGENT; WATER EXCHANGE; MRI; ANTITUMOR; CANCER; PERMEABILITY; RECEPTOR AB Antiangiogenesis is emerging as efficient strategy for targeting and potentially eliminating neoplastic tumor vessels. The main goal of this study was to establish whether absolute tumor blood volume (V-b) change could be used as an early predictor of antiangiogenesis in ectopic and orthotopic colon carcinomas. To assess therapy-induced changes of V-b, we did comparative analysis of signal intensities in tumors and muscle using steady-state magnetic resonance imaging (MRI) assisted with an intravascular paramagnetic contrast agent [gadolinium-labeled protected graft copolymer (PGC-Gd)]. Athymic mice with implanted human MV522 tumors were treated with vascular endothelial growth factor type 2 receptor tyrosine kinase inhibitor (VEGFR2-TKI) that has been shown to inhibit VEGFR2 phosphorylation and tumor growth in vivo. Animals were imaged either after a single day or after a I-week course of treatments. The measured V-b in ectopic tumors was 2.5 +/- 1.5% of total tissue volume I week after the implantation (n = 8). Two doses of VEGFR2-TKI (25 mg/kg, p.o., b.i.d.) resulted in a decrease of V-b to 1.3 +/- 0.3%. In orthotopic tumors, the measured V-b was initially higher (11.9 +/- 2.0%); however, VEGFR2-TKI treatment also resulted in a statistically significant decrease of V-b. The absolute V-b was not affected in the muscle as a result of treatments. MRI measurements were corroborated by using isotope and correlative histology experiments. Our results show that steady-state MRI is highly sensitive to early antiangiogenic effects caused by small molecule drugs. C1 Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA USA. RP Bogdanov, AA (reprint author), Univ Massachusetts, Sch Med, Dept Radiol, 55 Lake Ave N, Worcester, MA 01655 USA. EM Alexei.Bogdanov@uinassmed.edu RI Reichardt, Wilfried/K-6727-2013 FU NCI NIH HHS [1P50CA86355-01, 5R01 CA74424-01] NR 46 TC 20 Z9 21 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 9253 EP 9260 DI 10.1158/0008-5472.CAN-03-2619 PG 8 WC Oncology SC Oncology GA 974BR UT WOS:000232566800025 PM 16230386 ER PT J AU Lamfers, MLM Gianni, D Tung, CH Idema, S Schagen, FHE Carette, JE Quax, PHA Van Beusechem, VW Vandertop, WP Dirven, CMF Chiocca, EA Gerritsen, WR AF Lamfers, MLM Gianni, D Tung, CH Idema, S Schagen, FHE Carette, JE Quax, PHA Van Beusechem, VW Vandertop, WP Dirven, CMF Chiocca, EA Gerritsen, WR TI Tissue inhibitor of metalloproteinase-3 expression from an oncolytic adenovirus inhibits matrix metalloproteinase activity In vivo without affecting antitumor efficacy in malignant glioma SO CANCER RESEARCH LA English DT Article ID HUMAN BRAIN-TUMORS; THYMIDINE KINASE GENE; GLIOBLASTOMA XENOGRAFTS; REPLICATING ADENOVIRUS; MELANOMA-CELLS; SUICIDE GENE; HSV-TK; GROWTH; THERAPY; CANCER AB Oncolytic adenoviruses exhibiting tumor-selective replication are promising anticancer agents. Insertion and expression of a transgene encoding tissue inhibitor of metalloproteinase-3 (TIMP-3), which has been reported to inhibit angiogenesis and tumor cell infiltration and induce apoptosis, may improve the antitumor activity of these agents. To assess the effects of TIMP-3 gene transfer to glioma cells, a replication-defective adenovirus encoding TIMP-3 (Ad.TIMP-3) was employed. Ad.TIMP-3 infection of a panel of glioma cell cultures decreased the proliferative capacity of these cells and induced morphologic changes characteristic for apoptosis. Next, a conditionally replicating adenovirus encoding TIMP-3 was constructed by inserting the TIMP-3 expression cassette into the E3 region of the adenoviral backbone containing a 24-bp deletion in E1A. This novel oncolytic adenovirus, Ad Delta 24TIMP-3, showed enhanced oncolytic activity on a panel of primary cell cultures and two glioma cell lines compared with the control oncolytic virus Ad Delta 24Luc. In vivo inhibition of matrix metalloproteinase (MMP) activity by Ad Delta 24TIMP-3 was shown in s.c. glioma xenografts. The functional activity of TIMP-3 was imaged noninvasively using a near-IR fluorescent MMP-2-activated probe. Tumoral MMP-2 activity was significantly reduced by 58% in the Ad Delta 24TIMP-3-treated tumors 24 hours after infection. A study into the therapeutic effects of combined oncolytic and antiproteolytic therapy was done in both a s.c. and an intracranial model for malignant glioma. Treatment of s.c. (U-87MG) or intracranial (U-87 delta EGFR) tumors with Ad Delta 24TIMP-3 and Ad Delta 24Luc both significantly inhibited tumor growth and prolonged survival compared with PBS-treated controls. However, expression of TIMP-3 in the context of Ad Delta 24 did not significantly affect the antitumor efficacy of this oncolytic agent. C1 Vrije Univ Amsterdam, Med Ctr, Dept Neurosurg, NL-1007 MB Amsterdam, Netherlands. Vrije Univ Amsterdam, Med Ctr, Dept Med Oncol, NL-1007 MB Amsterdam, Netherlands. Vrije Univ Amsterdam, Med Ctr, Div Gene Therapy, NL-1007 MB Amsterdam, Netherlands. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Mol Neurooncol Labs,Neurosurg Serv, Charlestown, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA USA. TNO, PG, Gaubius Lab, NL-2300 AK Leiden, Netherlands. Ohio State Univ, Ctr Comprehens Canc, Dept Neurol Surg, Dardinger Ctr Neurooncol, Columbus, OH 43210 USA. RP Lamfers, MLM (reprint author), Vrije Univ Amsterdam, Med Ctr, Dept Neurosurg, Boelelaan, NL-1007 MB Amsterdam, Netherlands. EM M.Lamfers@vumc.nl RI Gerritsen, W.R./H-8031-2014; Lamfers, Martine/C-6246-2016; OI Lamfers, Martine/0000-0001-7745-9029; Quax, Paul/0000-0002-6853-5760; Tung, Ching-Hsuan/0000-0001-6648-6195 NR 56 TC 39 Z9 42 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 9398 EP 9405 DI 10.1158/0008-5472.CAN-04-4264 PG 8 WC Oncology SC Oncology GA 974BR UT WOS:000232566800042 PM 16230403 ER PT J AU Chiaretti, S Li, XC Gentleman, R Vitale, A Wang, KS Mandelli, F Foa, R Ritz, J AF Chiaretti, S Li, XC Gentleman, R Vitale, A Wang, KS Mandelli, F Foa, R Ritz, J TI Gene expression profiles of B-lineage adult acute lymphocytic leukemia reveal genetic patterns that identify lineage derivation and distinct mechanisms of transformation SO CLINICAL CANCER RESEARCH LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; FLT3 MUTATIONS; MLL REARRANGEMENTS; CHILDHOOD LEUKEMIA; MYELOID-LEUKEMIA; TYROSINE KINASE; BCR-ABL; SIGNATURES; CLASSIFICATION; INHIBITION AB Purpose: To characterize gene expression signatures in acute lymphocytic leukemia (ALL) cells associated with known genotypic abnormalities in adult patients. Experimental Design: Gene expression profiles from 128 adult patients with newly diagnosed ALL were characterized using high-density oligonucleotide microarrays. All patients were enrolled in the Italian GIMEMA multicenter clinical trial 0496 and samples had > 90% leukemic cells. Uniform phenotypic, cytogenetic, and molecular data were also available for all cases. Results: T-lineage ALL was characterized by a homogeneous gene expression pattern, whereas several subgroups of B-lineage ALL were evident. Within B-lineage ALL, distinct signatures were associated with ALL1/AF4 and E2A/PBX1 gene rearrangements. Expression profiles associated with ALL1/AF4 and E2A/PBX1 are similar in adults and children. BCR/ABL(+) gene expression pattern was more heterogeneous and was most similar to ALL without known molecular rearrangements. We also identified a set of 83 genes that were highly expressed in leukemia blasts from patients without known molecular abnormalities who subsequently relapsed following therapy. Supervised analysis of kinase genes revealed a high-level FLT3 expression in a subset of cases without molecular rearrangements. Two other kinases (PRKCB1 and DDR1) were highly expressed in cases without molecular rearrangements, as well as in BCR/ABL-positive ALL. Conclusions: Genomic signatures are associated with phenotypically and molecularly well defined subgroups of adult ALL. Genomic profiling also identifies genes associated with poor outcome in cases without molecular aberrations and specific genes that may be new therapeutic targets in adult ALL. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA USA. Univ Roma La Sapienza, Dept Cellular Biotechnol & Hematol, Div Hematol, Rome, Italy. RP Ritz, J (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM jerome_ritz@dfci.harvard.edu RI Ritz, Jerome/C-7929-2009 OI Ritz, Jerome/0000-0001-5526-4669 FU NCI NIH HHS [CA66996] NR 49 TC 70 Z9 77 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT 15 PY 2005 VL 11 IS 20 BP 7209 EP 7219 DI 10.1158/1078-0432.CCR-04-2165 PG 11 WC Oncology SC Oncology GA 976NB UT WOS:000232739200003 PM 16243790 ER PT J AU Leleu, X Le Friec, G Facon, T Amiot, L Fauchet, R Hennache, B Coiteux, V Yakoub-Agha, I Dubucquoi, S Avet-Loiseau, H Mathiot, C Bataille, R Mary, JY AF Leleu, X Le Friec, G Facon, T Amiot, L Fauchet, R Hennache, B Coiteux, V Yakoub-Agha, I Dubucquoi, S Avet-Loiseau, H Mathiot, C Bataille, R Mary, JY CA Intergroupe Francophone Myelome TI Total soluble HLA class I and soluble HLA-G in multiple myeloma and monoclonal gammopathy of undetermined significance SO CLINICAL CANCER RESEARCH LA English DT Article ID STAGING SYSTEM; G EXPRESSION; HEAVY-CHAIN; CELLS; LEUKEMIA; BETA(2)-MICROGLOBULIN; BETA-2-MICROGLOBULIN; METALLOPROTEINASE; GENERATION; DISORDERS AB Serum 2-microglobulin, the light chain of the HLA class I molecular complex, remains one of the best survival prognostic factors in multiple myeloma, but other HLA class I molecules might be of interest in monoclonal gammopathies. In this study, we evaluate total soluble HLA class I (HLA-Is) and soluble HILA-G (HLA-Gs) in 103 patients with newly diagnosed multiple myeloma, 30 patients with monoclonal gammopathy of undetermined significance (MGUS), and 30 healthy subjects, studying their prognostic value in multiple myeloma. In multiple myeloma patients, HLA-Is and HLA-Gs median values were 0.8 mu g/mL and 28 ng/mL, respectively. Median HLA-Is concentration was higher in stage 11 and III multiple myeloma patients than in stage I multiple myeloma, MGUS, and control patients. Median HLA-Gs was significantly lower in healthy controls than in MGUS and multiple myeloma patients. A high level of HLA-Is (>= 2.1 mu g/mL) was predictive of short survival (P = 0.017). Foreach given level of beta(2)-microglobulin, the relative risk of death was higher for patients with HLA-Is, 2.1 mu g/mL than in patients with a lower level (P = 0.047). HLA-Gs, a marker of monoclonal gammopathy, was of no prognostic value, but the addition of HLA-Is to beta(2)-microglobulin produced an efficient prognostic score (P < 0.0001). HILA-Is is a new marker of multiple myeloma tumor load and provides additional survival prognostic information to beta(2)-microglobulin. C1 Serv Hematol, Lille, France. Biochim Lab, Lille, France. Harvard Univ, Sch Med, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Bing Program Waldenstroms Macroglobulinemia, Boston, MA 02115 USA. Dana Farber Canc Inst, Jerome Lipper Myeloma Ctr, Boston, MA 02115 USA. Lab Hematol & Biol Cellules Sanguines, Rennes, France. Washington Univ, Sch Med, St Louis, MO USA. Univ Paris 07, Hop St Louis, INSERM U717, Paris, France. Inst Curie, Hematol Lab, Paris, France. Hematol Lab, Nantes, France. RP Facon, T (reprint author), Ctr Hosp Reg & Univ Lille, Hop Huriez, Serv Malad Sang, Rue Michel Polonovski, F-59037 Lille, France. EM t-facon@chru-lille.fr RI FACON, THIERRY/M-9736-2014; Amiot, laurence/J-5955-2015 OI FACON, THIERRY/0000-0001-7705-8460; NR 32 TC 38 Z9 40 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 7297 EP 7303 DI 10.1158/1078-0432.CCR-05-0456 PG 7 WC Oncology SC Oncology GA 976NB UT WOS:000232739200013 PM 16243800 ER PT J AU Martin, SI Zukerberg, L Robbins, GK AF Martin, SI Zukerberg, L Robbins, GK TI Reactive Epstein-Barr virus-related polyclonal lymphoproliferative disorder in a patient with AIDS SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; NON-HODGKINS-LYMPHOMA; INFECTED PATIENTS; CHILDREN; THERAPY; RESPONSES; DISEASE; LOAD; DNA AB Reactivation of Epstein-Barr virus infection and polyclonal expansion of lymphocytes is well-documented in solid organ and hematopoietic stem cell transplant recipients and is considered a potential precursor to lymphoma. We report an analogous case of posttransplantation polyclonal lymphoproliferative disorder in a patient with human immunodeficiency virus infection who was successfully treated with antiretroviral therapy. C1 Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Martin, SI (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St,GRJ-504, Boston, MA 02114 USA. EM simartin@partners.org RI Martin, Stanley/E-3600-2011 NR 19 TC 8 Z9 8 U1 1 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 E76 EP E79 DI 10.1086/444564 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 966EJ UT WOS:000232002300030 PM 16163622 ER PT J AU Benn, CL Landles, C Li, H Strand, AD Woodman, B Sathasivam, K Li, SH Ghazi-Noori, S Hockly, E Faruque, SMNN Cha, JHJ Sharpe, PT Olson, JM Li, XJ Bates, GP AF Benn, CL Landles, C Li, H Strand, AD Woodman, B Sathasivam, K Li, SH Ghazi-Noori, S Hockly, E Faruque, SMNN Cha, JHJ Sharpe, PT Olson, JM Li, XJ Bates, GP TI Contribution of nuclear and extranuclear polyQ to neurological phenotypes in mouse models of Huntington's disease SO HUMAN MOLECULAR GENETICS LA English DT Article ID NEURONAL INTRANUCLEAR INCLUSIONS; AMINO-ACID-SEQUENCE; TRANSGENIC MICE; MUTANT HUNTINGTIN; GENE-EXPRESSION; AXONAL-TRANSPORT; EXPORT SIGNAL; IN-VIVO; POLYGLUTAMINE; HD AB In postmortem Huntington's disease brains, mutant htt is present in both nuclear and cytoplasmic compartments. To dissect the impact of nuclear and extranuclear mutant htt on the initiation and progression of disease, we generated a series of transgenic mouse lines in which nuclear localization or nuclear export signal sequences have been placed N-terminal to the htt exon 1 protein carrying 144 glutamines. Our data indicate that the exon 1 mutant protein is present in the nucleus as part of an oligomeric or aggregation complex. Increasing the concentration of the mutant transprotein in the nucleus is sufficient for and dramatically accelerates the onset and progression of behavioral phenotypes. Furthermore, nuclear exon 1 mutant protein is sufficient to induce cytoplasmic neurodegeneration and transcriptional dysregulation. However, our data suggest that cytoplasmic mutant exon 1 htt, if present, contributes to disease progression. C1 Guys Hosp, Univ London Kings Coll, GKT Sch Med, London SE1 9RT, England. Emory Univ, Dept Genet, Atlanta, GA 30322 USA. Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. Univ London Kings Coll, Sch Dent, London SE1 9RT, England. Harvard Univ, Sch Med, Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Boston, MA 02139 USA. RP Bates, GP (reprint author), Guys Hosp, Univ London Kings Coll, GKT Sch Med, 8th Floor Guys Tower, London SE1 9RT, England. EM gillian.bates@genetics.kcl.ac.uk RI Bates, Gillian/E-1146-2012 OI Bates, Gillian/0000-0002-4041-6305 FU NIA NIH HHS [AG19206]; NINDS NIH HHS [NS45242, NS38106, NS41669]; Wellcome Trust NR 45 TC 63 Z9 63 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD OCT 15 PY 2005 VL 14 IS 20 BP 3065 EP 3078 DI 10.1093/hmg/ddi340 PG 14 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 972AG UT WOS:000232425600012 PM 16183657 ER PT J AU Cusick, ME Klitgord, N Vidal, M Hill, DE AF Cusick, ME Klitgord, N Vidal, M Hill, DE TI Interactome: gateway into systems biology SO HUMAN MOLECULAR GENETICS LA English DT Review ID PROTEIN-PROTEIN INTERACTIONS; TRANSCRIPTION FACTOR GENES; YEAST 2-HYBRID SYSTEM; ORFEOME VERSION 1.1; C-ELEGANS ORFEOME; FULL-LENGTH HUMAN; INTERACTION NETWORKS; SACCHAROMYCES-CEREVISIAE; INTERACTION MAP; CAENORHABDITIS-ELEGANS AB Protein-protein interactions are fundamental to all biological processes, and a comprehensive determination of all protein-protein interactions that can take place in an organism provides a framework for understanding biology as an integrated system. The availability of genome-scale sets of cloned open reading frames has facilitated systematic efforts at creating proteome-scale data sets of protein-protein interactions, which are represented as complex networks or 'interactome' maps. Protein-protein interaction mapping projects that follow stringent criteria, coupled with experimental validation in orthogonal systems, provide high-confidence data sets immanently useful for interrogating developmental and disease mechanisms at a system level as well as elucidating individual protein function and interactome network topology. Although far from complete, currently available maps provide insight into how biochemical properties of proteins and protein complexes are integrated into biological systems. Such maps are also a useful resource to predict the function(s) of thousands of genes. C1 Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Cusick, ME (reprint author), Dana Farber Canc Inst, Ctr Canc Syst Biol, 44 Binney St, Boston, MA 02115 USA. EM Michael_cusick@dfci.harvard.edu; marc_vidal@dfci.harvard.edu; david_hill@dfci.harvard.edu RI Klitgord, Niels/B-5121-2009; Hill, David/B-6617-2011 NR 141 TC 198 Z9 209 U1 0 U2 26 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 EI 1460-2083 J9 HUM MOL GENET JI Hum. Mol. Genet. PD OCT 15 PY 2005 VL 14 SI 2 BP R171 EP R181 DI 10.1093/hmg/ddi335 PG 11 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 980HS UT WOS:000233006400003 PM 16162640 ER PT J AU Cao, P Xia, ZN Song, W Zhang, SQ AF Cao, P Xia, ZN Song, W Zhang, SQ TI Neutralizing human anti-B-cell-activating factor of the TNF family (BAFF) scFv selected from phage antibody library SO IMMUNOLOGY LETTERS LA English DT Article DE phage display; BAFF; single-chain antibody fragment (scFv); autoimmune diseases ID NECROSIS-FACTOR FAMILY; LYMPHOCYTE STIMULATOR; FILAMENTOUS PHAGE; MONOCLONAL-ANTIBODY; AUTOIMMUNE-DISEASE; DISPLAY LIBRARIES; SJOGRENS-SYNDROME; AFFINITY; LIGAND; MEMBER AB Elevated levels of B-cell-activating factor of the TNF family (BAFF) have been implicated in the pathogenesis of autoimmune diseases in human. We now report the isolation by phage display of human single-chain antibody fragment (scFv) anti-BAFF. After four rounds of panning against BAFF, thirty-two out of 92 phage clones displayed BAFF binding activity. One of the positive clones, designated F8, bound to BAFF with relatively high affinity and neutralized BAFF bioactivity in vitro. F8 clone was expressed in soluble form in Escherichia coli HB2151 and purified by immobilized metal affinity chromatography (IMAC). The purified scFv recognized BAFF with the affinity constant (K-aff) of 2.5 x 10(7) M-1 without cross-reaction to APRIL. In addition to binding, the purified scFv could does-dependently inhibit BAFF-induced mouse spleen B lymphocyte proliferation. Together with its fully human mature, F8 scFv may have therapeutic implications in therapy of autoimmune disorders mediated by BAFF. (c) 2005 Elsevier B.V. All rights reserved. C1 Nanjing Normal Univ, Jiang Su Province Key Lab Mol & Med Biotechnol, Life Sci Coll, Nanjing 210097, Peoples R China. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Zhang, SQ (reprint author), Nanjing Normal Univ, Jiang Su Province Key Lab Mol & Med Biotechnol, Life Sci Coll, Nanjing 210097, Peoples R China. EM pcao79@yahoo.com; zhangshuangquan@263.net NR 29 TC 12 Z9 15 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-2478 J9 IMMUNOL LETT JI Immunol. Lett. PD OCT 15 PY 2005 VL 101 IS 1 BP 87 EP 94 DI 10.1016/j.imlet.2005.05.001 PG 8 WC Immunology SC Immunology GA 972VD UT WOS:000232480400012 PM 15939481 ER PT J AU Tantivejkul, K Loberg, RD Mawocha, SC Day, LL St John, L Pienta, BA Rubin, MA Pienta, KJ AF Tantivejkul, K Loberg, RD Mawocha, SC Day, LL St John, L Pienta, BA Rubin, MA Pienta, KJ TI PAR1-mediated NF kappa B activation promotes survival of prostate cancer cells through a Bcl-xL-dependent mechanism SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE prostate cancer; survival; PAR1; Bcl-xL; cytokines ID TUMOR-CELLS; CONSTITUTIVE ACTIVATION; LEUKOCYTE RECRUITMENT; INCREASED EXPRESSION; ENDOTHELIAL-CELLS; CARCINOMA CELLS; DOWN-REGULATION; P38 MAPK; THROMBIN; KINASE AB We have previously reported that protease-activated receptor 1 (PARI or thrombin receptor) is overexpressed in metastatic Prostate cancer cell lines compared to prostate epithelial cells. In this Study, we examined 1,074 prostate biopsies by tissue microarray analysis and demonstrated that PAR1 expression is significantly increased in prostate cancer compared to normal prostate epithelial cells and benign prostatic hyperplasia. We hypothesized that PAR1 activation contributed to prostate cancer cell progression. We demonstrated that stimulation of PAR1 by thrombin or thrombin receptor activating peptide (TRAP6), in androgen-independent DU145 and PC-3 cells resulted in increased DNA binding activity of the NF kappa B p65 Subunit. IL-6 and IL-8 levels were also elevated in conditioned media by at least two-fold within 4-6 h of PARI activation. This induction of cytokine production was abrogated by pretreatment of cells with the NF kappa B inhibitor caffeic acid phorbol ester. The p38 and ERK1/2 MAPK signaling cascades were also activated by PAR1 stimulation, whereas the SAPK/JNK pathway was unaffected. Inhibition of p38 and ERK1/2 by SB-203589 and PD-098059, respectively, did not abrogate NF kappa B activity, suggesting an independent induction of NF kappa B by PARI stimulation. Furthermore, TUNEL assay showed that activation of PAR1 attenuated docetaxel induced apoptosis through the upregulation of the Bcl-2 family protein Bcl-xL. Akt activation was not observed, suggesting that drug resistance induced by PAR1 was independent of PI3K signaling pathway. Because thrombin and PAR1 are over-expressed in prostate cancer patients, targeting the inhibition of their interaction may attenuate NF kappa B signaling transduction resulting in decreased drug resistance and subsequent survival of prostate cancer cells. C1 Univ Michigan, Dept Urol, Urol Ctr, Ann Arbor, MI 48109 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Michigan, Dept Internal Med, Div Hematol & Oncol, Ann Arbor, MI 48109 USA. RP Tantivejkul, K (reprint author), Univ Michigan, Dept Urol, Urol Ctr, 1500 E Med Ctr Dr,7431 CCGC, Ann Arbor, MI 48109 USA. EM ktantive@umich.edu RI Pienta, Kenneth/E-7679-2015 OI Pienta, Kenneth/0000-0002-4138-2186 FU NCI NIH HHS [1PO1 CA093900-01A2] NR 44 TC 52 Z9 55 U1 0 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD OCT 15 PY 2005 VL 96 IS 3 BP 641 EP 652 DI 10.1002/jcb.20533 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 969VG UT WOS:000232262800019 PM 16052512 ER PT J AU Vianello, F Kraft, P Mok, YT Hart, WK White, N Poznansky, MC AF Vianello, F Kraft, P Mok, YT Hart, WK White, N Poznansky, MC TI A CXCR4-dependent chemorepellent signal contributes to the emigration of mature single-positive CD4 cells from the fetal thymus SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CHEMOKINE RECEPTOR CXCR4; SPHINGOSINE 1-PHOSPHATE RECEPTOR; T-CELLS; THYMOCYTE EMIGRATION; LYMPHOCYTE ADHESION; ACTIVE MOVEMENT; FACTOR-I; CCR7; EMIGRANTS; MIGRATION AB Developing thymocytes undergo maturation while migrating through the thymus and ultimately emigrate from the organ to populate peripheral lymphoid tissues. The process of thymic emigration is controlled in part via receptor-ligand interactions between the chemokine stromal-derived factor (SDF)-1, and its cognate receptor CXCR4, and sphingosine 1-phosphate (S1P) and its receptor S1PR. The precise mechanism by which S1P/S1PR and CXCR4/SDF-1 contribute to thymic emigration remains unclear. We proposed that S1P-dependent and -independent mechanisms might coexist and involve both SIP-induced chemoattraction and SDF-1-mediated chemorepulsion or fugetaxis of mature thymocytes. We examined thymocyte emigration in thymi from CXCR4-deficient C57BL/6 embryos in a modified assay, which allows the collection of CD62L(high) and CD69(low) recent thymic emigrants. We demonstrated that single-positive (SP) CD4 thymocytes, with the characteristics of recent thymic emigrants, failed to move away from CXCR4-deficient fetal thymus in vitro. We found that the defect in SP CD4 cell emigration that occurred in the absence of CXCR4,signaling was only partially overcome by the addition of the extrathymic chemoattractant SIP and was not associated with abnormalities in thymocyte maturation and proliferative capacity or integrin expression. Blockade of the CXCR4 receptor in normal thymocytes by AMD3100 led to the retention of mature T cells in the thymus in vitro and in vivo. The addition of extrathymic SDF-1 inhibited emigration of wild-type SP cells out of the thymus by nullifying the chemokine gradient. SDF-1 was also shown to elicit a CXCR4-dependent chemorepellent response from fetal SP thymocytes. These novel findings support the thesis that the CXCR4-mediated chemorepellent activity of intrathymic SDF-1 contributes to SP thymocyte egress from the fetal thymus. C1 Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Massachusetts Gen Hosp Canc Ctr, Charlestown, MA 02129 USA. RP Poznansky, MC (reprint author), Massachusetts Gen Hosp, Partners AIDS Res Ctr, Bldg 149,13th St,5th Floor, Charlestown, MA 02129 USA. EM mpoznansky@partners.org RI Vianello, Fabrizio/M-5211-2016 OI Vianello, Fabrizio/0000-0002-7174-4651 FU NIAID NIH HHS [R01 AI49757, R21 AI049858] NR 48 TC 36 Z9 40 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 15 PY 2005 VL 175 IS 8 BP 5115 EP 5125 PG 11 WC Immunology SC Immunology GA 972GY UT WOS:000232443500034 PM 16210615 ER PT J AU Mukherjee, S Kashino, SS Zhang, YN Daifalla, N Rodrigues, V Reed, SG Campos-Neto, A AF Mukherjee, S Kashino, SS Zhang, YN Daifalla, N Rodrigues, V Reed, SG Campos-Neto, A TI Cloning of the gene encoding a protective Mycobacterium tuberculosis secreted protein detected in vivo during the initial phases of the infectious process SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CULTURE FILTRATE PROTEINS; EXTRACELLULAR PROTEINS; GEL ELECTROPHORESIS; EXPRESSION CLONING; VACCINATION; MICE; IMMUNITY; ANTIGEN; BCG; IMMUNIZATION AB The existence of therapeutic agents and the bacille Calmette-Guerin (BCG) vaccine have not significantly affected the current tuberculosis pandemic. BCG vaccine protects against serious pediatric forms of tuberculosis but not against adult pulmonary tuberculosis, the most common and contagious form of the disease. Several vaccine candidates, including Mycobacterium tuberculosis recombinant proteins formulated in newer adjuvants or delivered in bacterial plasmid DNA have recently been described. An attractive source of vaccine candidates has been M. tuberculosis Ags present in culture supernatants of the initial phases of the bacterial growth in vitro. In this study we describe an Ag discovery approach to select for such Ags produced in vivo during the initial phases of the infection. We combined RP-HPLC and mass spectrometry to identify secreted or shed M. tuberculosis proteins eliminated in animal urine within 14 days after the infection. A peptide containing sequence homology with a hypothetical M. tuberculosis protein was identified and the recombinant protein produced in Escherichia coli. The protein was recognized by Ab (IgG2a and IgG1) and T cells (Th1) of mice infected with M. tuberculosis and by lymphoid cells from healthy donors who had a positive purified protein derivative skin test but not from tuberculosis patients. Moreover, this Ag induced protection in mice against M. tuberculosis at levels comparable to protection induced by BCG vaccine. These results validate the Ag discovery approach of M. tuberculosis proteins secreted or shed in vivo during the early phases of the infection and open new possibilities for the development of potential vaccine candidates or of markers of active mycobacterial multiplication: and therefore active disease. C1 Forsyth Inst, Boston, MA 02115 USA. Infect Dis Res Inst, Seattle, WA 98104 USA. Corixa Corp, Dept Proc Sci, Seattle, WA 98101 USA. Med Sch Triangulo Mineiro, Uberaba, MG, Brazil. Univ Washington, Dept Pathobiol, Seattle, WA 98195 USA. RP Campos-Neto, A (reprint author), Forsyth Inst, 140 Fenway, Boston, MA 02115 USA. EM acampos@forsyth.org RI Kashino, Suely/F-4171-2012; Daifalla, Nada/E-6005-2017 FU NIAID NIH HHS [AI 43528, AI 44373] NR 37 TC 11 Z9 12 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 15 PY 2005 VL 175 IS 8 BP 5298 EP 5305 PG 8 WC Immunology SC Immunology GA 972GY UT WOS:000232443500054 PM 16210635 ER PT J AU Jen, J Baloh, RH Ishiyama, A Baloh, RW AF Jen, J Baloh, RH Ishiyama, A Baloh, RW TI Dejerine-Sottas syndrome and vestibular loss due to a point mutation in the PMP22 gene SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Article DE Charcot-Marie-Tooth; hearing loss; imbalance; oscillopsia ID MARIE-TOOTH-DISEASE; DEAFNESS AB We describe a father and daughter with Dejerine-Sottas syndrome and bilateral vestibular loss due to an L71P missense mutation in the peripheral myelin protein 22 (PMP22). The combination of vestibular loss and peripheral neuropathy led to profound imbalance at a young age. It is important to recognize this combination of peripheral nerve and vestibular deficits since rehabilitation strategies and prognosis are different. (c) 2005 Elsevier B.V. All rights reserved. C1 Univ Calif Los Angeles, Dept Neurol, Sch Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Dept Surg, Los Angeles, CA USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Baloh, RW (reprint author), Univ Calif Los Angeles, Dept Neurol, Sch Med, Box 951769, Los Angeles, CA 90095 USA. EM rwbaloh@ucla.edu FU NIDCD NIH HHS [DC05224] NR 11 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD OCT 15 PY 2005 VL 237 IS 1-2 BP 21 EP 24 DI 10.1016/j.jns.2005.05.003 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 974IL UT WOS:000232584800004 PM 15992829 ER PT J AU Jackman, DM Johnson, BE AF Jackman, DM Johnson, BE TI Small-cell lung cancer SO LANCET LA English DT Review ID EATON-MYASTHENIC-SYNDROME; PROPHYLACTIC CRANIAL IRRADIATION; MULTICENTER RANDOMIZED-TRIAL; COOPERATIVE-ONCOLOGY-GROUP; GASTRIN-RELEASING-PEPTIDE; COLONY-STIMULATING FACTOR; LONG-TERM SURVIVAL; ACID RECEPTOR-BETA; PHASE-III TRIAL; INTENSIVE WEEKLY CHEMOTHERAPY AB Small-cell lung carcinoma is an aggressive form of lung cancer that is strongly associated with cigarette smoking and has a tendency for early dissemination. Increasing evidence has implicated autocrine growth loops, proto-oncogenes, and tumour-suppressor genes in its development. At presentation, the vast majority of patients are symptomatic, and imaging typically reveals a hilar mass. Pathology, in most cases of samples obtained by bronchoscopic biopsy, should be undertaken by pathologists with pulmonary expertise, with the provision of additional tissue for immunohistochemical stains as needed. Staging should aim to identify any evidence of distant disease, by imaging of the chest, upper abdomen, head, and bones as appropriate. Limited-stage disease should be treated with etoposide and cisplatin and concurrent early chest irradiation. All patients who achieve complete remission should be considered for treatment with prophylactic cranial irradiation, owing to the high frequency of brain metastases in this disease. Extensive-stage disease should be managed by combination chemotherapy, with a regimen such as etoposide and cisplatin administered for four to six cycles. Thereafter, patients with progressive or recurrent disease should be treated with additional chemotherapy. For patients who survive long term, careful monitoring for development of a second primary tumour is necessary, with further investigation and treatment as appropriate. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Jackman, DM (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM djackman@partners.org NR 157 TC 264 Z9 286 U1 2 U2 20 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD OCT 15 PY 2005 VL 366 IS 9494 BP 1385 EP 1396 DI 10.1016/S0140-6736(05)67569-1 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 973ZW UT WOS:000232562100031 PM 16226617 ER PT J AU Pham, W Zhao, BQ Lo, EH Medarova, Z Rosen, B Moore, A AF Pham, W Zhao, BQ Lo, EH Medarova, Z Rosen, B Moore, A TI Crossing the blood-brain barrier: A potential application of myristoylated polyarginine for in vivo neuroimaging SO NEUROIMAGE LA English DT Article DE blood-brain barrier; myristoylated polyarginine; in vivo neuroimaging ID BINDING AB As basic neurological research continues to reveal novel targets for therapy, the need to deliver therapeutic agents across the blood-brain barrier (BBB) becomes increasingly important. If developed, delivery modules would bring targeting molecules across the BBB to their respective active sites. In addition, it would be highly advantageous if the bioavailability of these delivered agents could be monitored over time using non-invasive imaging techniques. Here, we describe a versatile delivery module based on a myristoylated polyarginine backbone, which crosses the BBB. Incorporation of the fatty acid group was achieved using a Schotten-Bauman reaction with quantitative yield, and the peptide was further synthesized by conventional solid phase peptide synthesis (SPPS). We report for the first time the in vivo distribution of the delivery module over time into mouse brain using near-infrared (NIR) fluorescence imaging. The fluorescent cargo was detected in vivo from 24-48 h post IV injection and was further characterized in perfused brains. Inummohistochemical staining of excised brain showed that the delivery module primarily accumulated in neurons with occasional localization in astrocytes and endothelial cells. We conclude that this approach can be used for the delivery of imaging probes and potentially targeted therapeutics across the BBB. (c) 2005 Elsevier Inc. All rights reserved. C1 Harvard Univ, MGH MIT HMS, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Radiol, Neuroprotect Res Lab, Boston, MA 02129 USA. Massachusetts Gen Hosp, Dept Neurol, Neuroprotect Res Lab, Boston, MA 02129 USA. Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02129 USA. RP Moore, A (reprint author), Harvard Univ, MGH MIT HMS, Charlestown, MA 02129 USA. EM amoore@helix.mgh.harvard.edu FU NCRR NIH HHS [RR1407506]; NHLBI NIH HHS [R01-HL39810]; NINDS NIH HHS [P50-NS10828, R01-NS37074, R01-NS38731, R01-NS40529] NR 10 TC 42 Z9 42 U1 0 U2 8 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD OCT 15 PY 2005 VL 28 IS 1 BP 287 EP 292 DI 10.1016/j.neuroimage.2005.06.007 PG 6 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 974XA UT WOS:000232623500029 PM 16040255 ER PT J AU Motz, JT Yelin, D Vakoc, BJ Bouma, BE Tearney, GJ AF Motz, JT Yelin, D Vakoc, BJ Bouma, BE Tearney, GJ TI Spectral- and frequency-encoded fluorescence imaging SO OPTICS LETTERS LA English DT Article ID MICROSCOPY; ENDOSCOPY; ANTIBODY; FIBER AB A method for obtaining fluorescence images with a high number of resolvable points by using spectral and frequency encoding is presented. Broadband excitation light is encoded with a wavelength-dependent frequency modulation and dispersed onto the sample with a grating to simultaneously illuminate an entire image line. The Fourier transform of the frequency-encoded fluorescence emission provides one line of the image. Mechanical scanning along a direction orthogonal to the wavelength-encoded axis allows creation of the two-dimensional fluorescent image. This method is applicable for developing submillimeter diameter endoscopes. The principles of the technique are validated by imaging indocyanine green fluorescence in microfluidic channels. (c) 2005 Optical Society ofAmerica C1 Harvard Univ, Sch Med, Wellman Ctr Photomed, Boston, MA 02114 USA. Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. Massachusetts Gen Hosp, Pathol Serv, Boston, MA 02114 USA. RP Motz, JT (reprint author), Harvard Univ, Sch Med, Wellman Ctr Photomed, 55 Fruit St,BAR 703, Boston, MA 02114 USA. EM jmotz@partners.org FU NIAMS NIH HHS [5 T32 AR07098] NR 13 TC 18 Z9 18 U1 2 U2 4 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 0146-9592 J9 OPT LETT JI Opt. Lett. PD OCT 15 PY 2005 VL 30 IS 20 BP 2760 EP 2762 DI 10.1364/OL.30.002760 PG 3 WC Optics SC Optics GA 973JG UT WOS:000232518100026 PM 16252766 ER PT J AU Rassovsky, Y Green, MF Nuechterlein, KH Breitmeyer, BG Mintz, J AF Rassovsky, Y Green, MF Nuechterlein, KH Breitmeyer, BG Mintz, J TI Visual processing in schizophrenia: Structural equation modeling of visual masking performance SO SCHIZOPHRENIA RESEARCH LA English DT Article DE visual masking; paracontrast; metacontrast; schizophrenia; neurocognition ID BACKWARD-MASKING; CHANNELS; METACONTRAST; PARACONTRAST; TRANSIENT; MECHANISM; DEFICITS; MANIA AB Schizophrenic patients consistently demonstrate performance deficits on visual masking procedures. In visual masking, the subject's ability to process a target stimulus is reduced by another stimulus (mask) presented either before (forward masking) or after (backward masking) the target. Masking procedures employed in schizophrenia research have used several experimental paradigms. Most early studies have used high-energy masks (i.e., the mask is stronger than the target) and spatially overlapping target and mask. More recently, studies have begun to employ relatively weak (i.e., low-energy) masks, as well as masks that surround, but do not spatially overlap, the target. Data for forward and backward masking components of four masking conditions (target location and identification with a high-energy mask, target identification with a low-energy mask, and target identification with equal energy paracontrast/metacontrast) were collected from 75 patients with schizophrenia. Based on theoretical distinctions among masking procedures, we compared four models of visual masking using structural equation modeling. Although high zero-order correlations were found among the masking parameters, a four-factor model, in which factors were separated on the type of response (target location and identification), the shape of the function (monotonic and nonmonotonic), and the overlap of the stimuli (overlapping and non-overlapping), provided the best fit for the data. These findings suggest that the four masking procedures used in this study may tap unique aspects of visual processing and are not redundant. The results also support theories of the different mechanisms underlying performance on these measures. (c) 2005 Elsevier B.V. All rights reserved. C1 Univ Calif Los Angeles, Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90024 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. Univ Houston, Dept Psychol, Houston, TX 77004 USA. RP Rassovsky, Y (reprint author), Univ Calif Los Angeles, Geffen Sch Med, Dept Psychiat & Biobehav Sci, 760 Westwood Plaza C8-747-NPI, Los Angeles, CA 90024 USA. EM yurir@ucla.edu FU NIMH NIH HHS [MH-43292, MH-65707] NR 31 TC 7 Z9 7 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD OCT 15 PY 2005 VL 78 IS 2-3 BP 251 EP 260 DI 10.1016/j.schres.2005.05.011 PG 10 WC Psychiatry SC Psychiatry GA 968PI UT WOS:000232174100016 PM 15975768 ER PT J AU Dickey, CC McCarley, RW Niznikiewicz, MA Voglmaier, MM Seidman, LJ Kim, S Shenton, ME AF Dickey, CC McCarley, RW Niznikiewicz, MA Voglmaier, MM Seidman, LJ Kim, S Shenton, ME TI Clinical, cognitive, and social characteristics of a sample of neuroleptic-naive persons with schizotypal personality disorder SO SCHIZOPHRENIA RESEARCH LA English DT Article DE schizophrenia; schizotypal personality disorder; gender; clinical; demographics; IQ ID NEUROPSYCHOLOGICAL TEST-PERFORMANCE; SCHIZOPHRENIC-PATIENTS; ROSCOMMON FAMILY; MRI; SYMPTOMS; ABNORMALITIES; RELATIVES; SPECTRUM; BRAIN; GYRUS AB Introduction: Schizotypal personality disorder (SPD) shares with schizophrenia many biological features, yet little is known about the clinical characteristics of persons diagnosed with this disorder. This report describes the clinical, cognitive and socio-occupational characteristics of a community sample of subjects diagnosed with SPD. Method: Sixty-four male and 40 female neuroleptic-naive DSM-IV SPD subjects and 59 male and 51 female comparison subjects were recruited from the community for a total sample of 214 subjects. Demographic and cognitive differences between groups and, within the SPD group, the effect of gender on clinical features, such as the SPD criteria, SAPS, SANS, Schizotypal Personality Questionnaire, and co-morbidity, were examined using ANOVA and Chi-square distributions. Results: SPD subjects, in contrast to comparison subjects, had significantly lower socio-economic status, poorer social relationships and skills, and lower vocabulary scores. Furthermore, SPD subjects demonstrated more impairment on Vocabulary scores than on Block Design, as measured by the WAIS-R, a pattern not seen in comparison subjects. In the SPD cohort, positive symptoms predominated and nearly half were co-morbid for major depression. With respect to gender, male SPD subjects, compared with female SPD subjects, evinced significantly more negative symptoms, fewer friends, had more odd speech, and were more likely to also suffer from paranoid and narcissistic personality disorders. In contrast to male SPD subjects, female SPD subjects perceived themselves to be more disorganized. Conclusions: SPD subjects, similar to schizophrenics, are impaired socially, occupationally, and cognitively, particularly in the area of verbal measures. Moreover, male SPD subjects may be more severely affected than female SPD subjects across multiple domains of functioning. (c) 2005 Elsevier B.V All rights reserved. C1 Harvard Univ, Sch Med, VA Boston Healthcare Syst, Lab Neurosci,Clin Neurosci Div, Boston, MA 02401 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Neurol, Boston, MA 02401 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02401 USA. Harvard Univ, Sch Med, Cambridge Hosp, Dept Psychiat, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Massachusetts Mental Hlth Ctr, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. RP Dickey, CC (reprint author), Harvard Univ, Sch Med, VA Boston Healthcare Syst, Lab Neurosci,Clin Neurosci Div, Psychiat 116A,940 Belmont St, Boston, MA 02401 USA. EM chandlee_dickey@hms.harvard.edu RI McCarley, Robert/N-5562-2014 OI McCarley, Robert/0000-0001-5705-7495 FU NIMH NIH HHS [MH40799, K02 MH001110, K02 MH001110-10, MH 01110, MH 50740, MH 52807, R01 MH040799, R01 MH050740, R01 MH050740-10, R01 MH052807] NR 39 TC 34 Z9 34 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD OCT 15 PY 2005 VL 78 IS 2-3 BP 297 EP 308 DI 10.1016/j.schres.2005.05.016 PG 12 WC Psychiatry SC Psychiatry GA 968PI UT WOS:000232174100021 PM 15985362 ER PT J AU Vaccaro, AR Lehman, RA Hurlbert, J Anderson, PA Harris, M Hedlund, R Harrop, J Dvorak, M Wood, K Fehlings, MG Fisher, C Zeiller, SC Anderson, DG Bono, CM Stock, GH Brown, AK Kuklo, T Oner, FC AF Vaccaro, AR Lehman, RA Hurlbert, J Anderson, PA Harris, M Hedlund, R Harrop, J Dvorak, M Wood, K Fehlings, MG Fisher, C Zeiller, SC Anderson, DG Bono, CM Stock, GH Brown, AK Kuklo, T Oner, FC TI A new classification of thoracolumbar injuries - The importance of injury morphology, the integrity of the posterior ligamentous complex, and neurologic status SO SPINE LA English DT Article DE spine trauma; thoracolumbar fractures; classification; clinical pathways ID FRACTURE-DISLOCATIONS; SPINE FRACTURES AB Study Design. A new proposed classification system for thoracolumbar (TL) spine injuries, including injury severity assessment, designed to assist in clinical management. Objective. To devise a practical, yet comprehensive, classification system for TL injuries that assists in clinical decision-making in terms of the need for operative versus nonoperative care and surgical treatment approach in unstable injury patterns. Summary of Background Data. The most appropriate classification of traumatic TL spine injuries remains controversial. Systems currently in use can be cumbersome and difficult to apply. None of the published classification schemata is constructed to aid with decisions in clinical management. Methods. Clinical spine trauma specialists from a variety of institutions around the world were canvassed with respect to information they deemed pivotal in the communication of TL spine trauma and the clinical decision-making process. Traditional injury patterns were reviewed and reconsidered in light of these essential characteristics. An initial validation process to determine the reliability and validity of an earlier version of this system was also undertaken. Results. A new classification system called the Thoracolumbar Injury Classification and Severity Score (TLICS) was devised based on three injury characteristics: 1) morphology of injury determined by radiographic appearance, 2) integrity of the posterior ligamentous complex, and 3) neurologic status of the patient. A composite injury severity score was calculated from these characteristics stratifying patients into surgical and nonsurgical treatment groups. Finally, a methodology was developed to determine the optimum operative approach for surgical injury patterns. Conclusions. Although there will always be limitations to any cataloging system, the TLICS reflects accepted features cited in the literature important in predicting spinal stability, future deformity, and progressive neurologic compromise. This classification system is intended to be easy to apply and to facilitate clinical decision-making as a practical alternative to cumbersome classification systems already in use. The TLICS may improve communication between spine trauma physicians and the education of residents and fellows. Further studies are underway to determine the reliability and validity of this tool. C1 Thomas Jefferson Univ, Dept Orthopaed Surg, Philadelphia, PA 19107 USA. Walter Reed Army Med Ctr, Dept Orthopaed Surg & Rehabil, Washington, DC 20307 USA. Univ Calgary, Spine Program, Calgary, AB, Canada. Foothills Hosp & Med Ctr, Dept Clin Neurosci, Calgary, AB, Canada. Univ Wisconsin, Dept Orthopaed Surg & Rehabil, Madison, WI USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Haddinge Univ Hosp, Karolinska Inst, Stockholm, Sweden. Thomas Jefferson Univ, Dept Neurosurg, Philadelphia, PA 19107 USA. Univ British Columbia, Dept Orthopaed, Div Spine, Vancouver, BC V5Z 1M9, Canada. Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. Univ Toronto, Univ Hlth Network, Dept Neurosurg, Toronto, ON, Canada. Boston Univ, Med Ctr, Dept Orthopaed Surg, Boston, MA USA. Univ Utrecht Hosp, Dept Orthoped, Utrecht, Netherlands. RP Vaccaro, AR (reprint author), Rothman Inst, 925 Chestnut St,5th Floor, Philadelphia, PA 19107 USA. EM alexvaccaro3@aol.com RI Oner, FC/L-7769-2013 OI Oner, FC/0000-0003-0858-8243 NR 21 TC 221 Z9 297 U1 1 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0362-2436 J9 SPINE JI SPINE PD OCT 15 PY 2005 VL 30 IS 20 BP 2325 EP 2333 DI 10.1097/01.brs.0000182986.43345.cb PG 9 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 975NS UT WOS:000232669800014 PM 16227897 ER PT J AU Switzer, GE Dew, MA Harrington, DJ Crowley-Matoka, M Myaskovsky, L Abress, L Confer, DL AF Switzer, GE Dew, MA Harrington, DJ Crowley-Matoka, M Myaskovsky, L Abress, L Confer, DL TI Ethnic differences in donation-related characteristics among potential hematopoietic stem cell donors SO TRANSPLANTATION LA English DT Article DE hematopoietic stem cell donation; ethnicity ID BONE-MARROW DONORS; TRANSPLANTATION; ATTRITION; RACE; WILLINGNESS; SELECTION; REGISTRY; ORGANS; STATE; CARE AB Background. Although the National Marrow Donor Program has been highly successful at recruiting ethnic minorities as potential hematopoietic stem cell donors, there have been no systematic investigations of whether donor characteristics that might be linked to the donation experience vary by ethnicity. Methods. Questionnaires assessing four domains-demographic, volunteer-related, general psychosocial, and donation-related-were mailed to potential donors after they were contacted as a preliminary match for a patient and had agreed to donate. in all, 1,679 potential donors completed and returned a predonation questionnaire. Data from potential donors belonging to five major ethnic groups were analyzed; white, black, Asian/Pacific Islander, Hispanic, and Native American. Results. Bivariate analyses indicated that virtually all factors in the four domains were associated with ethnicity. Direct discriminant function analysis identified three significant functions. The most striking of the three functions indicated that Asian Americans were more highly educated, more ambivalent (reluctant about donation), more concerned (medical, work/family), and more anxious and depressed than all other ethnic groups. Key differences among other ethnic group members were also identified. Conclusions. This study provides the first evidence of ethnic group differences in key predonation variables. Findings suggest that Asian/Pacific Islanders possess a number of characteristics that are known psychosocial risk factors for less positive postdonation outcomes and that more intensive pre and postdonation contact with this group may be necessary. Strategies for improving future research in this area are discussed. C1 Univ Pittsburgh, Dept Med, Ctr Res Hlth Care, Pittsburgh, PA 15213 USA. VA Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA USA. Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Psychol, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15260 USA. Natl Marrow Donor Program, Minneapolis, MN USA. RP Switzer, GE (reprint author), Univ Pittsburgh, Dept Med, Ctr Res Hlth Care, Iroquois Bldg,Suite 502,3600 Forbes Ave, Pittsburgh, PA 15213 USA. EM SwitzerGE@upmc.edu FU NHLBI NIH HHS [R29-HL56901] NR 25 TC 13 Z9 13 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD OCT 15 PY 2005 VL 80 IS 7 BP 890 EP 896 DI 10.1097/01.TP.0000173648.60978.30 PG 7 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 978YL UT WOS:000232908900003 PM 16249735 ER PT J AU Abelson, JF Kwan, KY O'Roak, BJ Baek, DY Stillman, AA Morgan, TM Mathews, CA Pauls, DA Rasin, MR Gunel, M Davis, NR Ercan-Sencicek, AG Guez, DH Spertus, JA Leckman, JF Dure, LS Kurlan, R Singer, HS Gilbert, DL Farhi, A Louvi, A Lifton, RP Sestan, N State, MW AF Abelson, JF Kwan, KY O'Roak, BJ Baek, DY Stillman, AA Morgan, TM Mathews, CA Pauls, DA Rasin, MR Gunel, M Davis, NR Ercan-Sencicek, AG Guez, DH Spertus, JA Leckman, JF Dure, LS Kurlan, R Singer, HS Gilbert, DL Farhi, A Louvi, A Lifton, RP Sestan, N State, MW TI Sequence variants in SLITRK1 are associated with Tourette's syndrome SO SCIENCE LA English DT Article ID BILINEAL TRANSMISSION; SIB PAIRS; FAMILY; EXPRESSION; INHERITANCE; MUTATIONS; LINKAGE; BRAIN AB Tourette's syndrome (TS) is a genetically influenced developmental neuropsychiatric disorder characterized by chronic vocal and motor tics. We studied Slit and Trk-like 1 (SLITRK1) as a candidate gene on chromosome 13q31.1 because of its proximity to a de novo chromosomal inversion in a child with TS. Among 174 unrelated probands, we identified a frameshift mutation and two independent occurrences of the identical variant in the binding site for microRNA hsa-miR-189. These variants were absent from 3600 control chromosomes. SLITRK1 mRNA and hsa-miR-189 showed an overlapping expression pattern in brain regions previously implicated in TS. Wild-type SLITRK1, but not the frameshift mutant, enhanced dendritic growth in primary neuronal cultures. Collectively, these findings support the association of rare SLITRK1 sequence variants with TS. C1 Yale Univ, Sch Med, Ctr Child Study, New Haven, CT 06520 USA. Yale Univ, Sch Med, Dept Genet, New Haven, CT 06520 USA. Yale Univ, Sch Med, Dept Neurobiol, New Haven, CT 06520 USA. Yale Univ, Sch Med, Interdepartmental Neurosci Program, New Haven, CT 06520 USA. Yale Univ, Sch Med, Dept Neurosurg, New Haven, CT 06520 USA. Yale Univ, Sch Med, Ctr Human Genet & Genom, New Haven, CT 06520 USA. Yale Univ, Sch Med, Howard Hughes Med Inst, New Haven, CT 06520 USA. Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. Univ Missouri, Dept Med, Kansas City, MO 64111 USA. Univ Alabama, Dept Pediat, Div Pediat Neurol, Birmingham, AL 35233 USA. Univ Rochester, Sch Med, Dept Neurol, Rochester, NY 14642 USA. Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21287 USA. Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21287 USA. Cincinnati Childrens Hosp Med Ctr, Div Neurol, Cincinnati, OH 45229 USA. RP State, MW (reprint author), Yale Univ, Sch Med, Ctr Child Study, 333 Cedar St, New Haven, CT 06520 USA. EM matthew.state@yale.edu RI Kwan, Kenneth/F-8489-2011; Morgan, Tom/C-3478-2012; Gilbert, Donald/D-6443-2016 OI Kwan, Kenneth/0000-0003-4711-071X; Gilbert, Donald/0000-0002-9245-6878 FU NCRR NIH HHS [K23 RR16118]; NINDS NIH HHS [R01 NS054273, R01 NS43520] NR 26 TC 572 Z9 613 U1 9 U2 31 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 14 PY 2005 VL 310 IS 5746 BP 317 EP 320 DI 10.1126/science.1116502 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 975NV UT WOS:000232670100053 PM 16224024 ER PT J AU Nelissen, K Luppino, G Vanduffel, W Rizzolatti, G Orban, GA AF Nelissen, K Luppino, G Vanduffel, W Rizzolatti, G Orban, GA TI Observing others: Multiple action representation in the frontal lobe SO SCIENCE LA English DT Article ID PREMOTOR CORTEX; MACAQUE; MONKEY; CONNECTIONS; MECHANISMS; SHAPE; AREA; F5 AB Observation of actions performed by-others activates monkey ventral premotor cortex, where action meaning, but not object identity, is coded. In a functional MRI (fMRI) study, we investigated whether other monkey frontal areas respond to actions performed by others. Observation of a hand grasping objects activated four frontal areas: rostral F5 and areas 45B, 45A, and 46. Observation of an individual grasping an object also activated caudal F5, which indicates,different degrees of action abstraction in F5. Observation of shapes activated area 45, but not premotor F5. Convergence of object and action information in area 45 may be important for full comprehension of actions. C1 Katholieke Univ Leuven, Sch Med, Lab Neuro Psychofysiol, Louvain, Belgium. Univ Parma, Dipartimento Neurosci, I-43100 Parma, Italy. Harvard Univ, Sch Med, Massachusetts Gen Hosp, MIT,Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Orban, GA (reprint author), Katholieke Univ Leuven, Sch Med, Lab Neuro Psychofysiol, Louvain, Belgium. EM guy.orban@med.kuleuven.ac.be NR 23 TC 206 Z9 211 U1 4 U2 10 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 14 PY 2005 VL 310 IS 5746 BP 332 EP 336 DI 10.1126/science.1115593 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 975NV UT WOS:000232670100058 PM 16224029 ER PT J AU Calvano, SE Xiao, WZ Richards, DR Felciano, RM Baker, HV Cho, RJ Chen, RO Brownstein, BH Cobb, JP Tschoeke, SK Miller-Graziano, C Moldawer, LL Mindrinos, MN Davis, RW Tompkins, RG Lowry, SF AF Calvano, SE Xiao, WZ Richards, DR Felciano, RM Baker, HV Cho, RJ Chen, RO Brownstein, BH Cobb, JP Tschoeke, SK Miller-Graziano, C Moldawer, LL Mindrinos, MN Davis, RW Tompkins, RG Lowry, SF CA Inflammation Host Response Injury TI A network-based analysis of systemic inflammation in humans SO NATURE LA English DT Article ID MITOCHONDRIAL PERMEABILITY TRANSITION; MOLECULAR CLASSIFICATION; ENDOTOXIN TOLERANCE; CELL-DEATH; EXPRESSION; DISEASE; DYSFUNCTION; MICROARRAYS; PREDICTION; MECHANISM AB Oligonucleotide and complementary DNA microarrays are being used to subclassify histologically similar tumours, monitor disease progress, and individualize treatment regimens(1-5). However, extracting new biological insight from high-throughput genomic studies of human diseases is a challenge, limited by difficulties in recognizing and evaluating relevant biological processes from huge quantities of experimental data. Here we present a structured network knowledge-base approach to analyse genome-wide transcriptional responses in the context of known functional interrelationships among proteins, small molecules and phenotypes. This approach was used to analyse changes in blood leukocyte gene expression patterns in human subjects receiving an inflammatory stimulus ( bacterial endotoxin). We explore the known genome-wide interaction network to identify significant functional modules perturbed in response to this stimulus. Our analysis reveals that the human blood leukocyte response to acute systemic inflammation includes the transient dysregulation of leukocyte bioenergetics and modulation of translational machinery. These findings provide insight into the regulation of global leukocyte activities as they relate to innate immune system tolerance and increased susceptibility to infection in humans. C1 Stanford Genome Technol Ctr, Palo Alto, CA 94304 USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Surg, New Brunswick, NJ 08903 USA. Ingenuity Syst Inc, Mountain View, CA 94043 USA. Univ Florida, Coll Med, Dept Mol Genet & Microbiol, Gainesville, FL 32610 USA. Univ Florida, Coll Med, Dept Surg, Gainesville, FL 32610 USA. Washington Univ, Dept Surg, St Louis, MO 63110 USA. Univ Rochester, Sch Med, Dept Surg, Rochester, NY 14642 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Davis, RW (reprint author), Stanford Genome Technol Ctr, Palo Alto, CA 94304 USA. EM dbowe@stanford.edu OI xiao, wenzhong/0000-0003-4944-6380; Baker, Henry/0000-0002-8273-5320 FU NIGMS NIH HHS [U54 GM062119] NR 24 TC 884 Z9 918 U1 9 U2 47 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 1032 EP 1037 DI 10.1038/nature03985 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 973AU UT WOS:000232496100047 PM 16136080 ER PT J AU Fujiwara, T Bandi, M Nitta, M Ivanova, EV Bronson, RT Pellman, D AF Fujiwara, T Bandi, M Nitta, M Ivanova, EV Bronson, RT Pellman, D TI Cytokinesis failure generating tetraploids promotes tumorigenesis in p53-null cells SO NATURE LA English DT Article ID MAMMALIAN-CELLS; CHROMOSOME INSTABILITY; TELOMERE DYSFUNCTION; CANCER PROGRESSION; GENOME INSTABILITY; P53; MODEL; TRANSLOCATIONS; SEGREGATION; SUPPRESSOR AB A long-standing hypothesis on tumorigenesis is that cell division failure, generating genetically unstable tetraploid cells, facilitates the development of aneuploid malignancies(1-3). Here we test this idea by transiently blocking cytokinesis in p53-null (p53(-/-)) mouse mammary epithelial cells (MMECs), enabling the isolation of diploid and tetraploid cultures. The tetraploid cells had an increase in the frequency of whole-chromosome mis-segregation and chromosomal rearrangements. Only the tetraploid cells were transformed in vitro after exposure to a carcinogen. Furthermore, in the absence of carcinogen, only the tetraploid cells gave rise to malignant mammary epithelial cancers when transplanted subcutaneously into nude mice. These tumours all contained numerous non-reciprocal translocations and an 8-30-fold amplification of a chromosomal region containing a cluster of matrix metalloproteinase (MMP) genes. MMP overexpression is linked to mammary tumours in humans and animal models(4). Thus, tetraploidy enhances the frequency of chromosomal alterations and promotes tumour development in p53(-/-) MMECs. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02115 USA. Tufts Univ, Sch Vet, Dept Biomed Sci, North Grafton, MA 01536 USA. RP Pellman, D (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. EM david_pellman@dfci.harvard.edu NR 30 TC 510 Z9 515 U1 1 U2 17 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 1043 EP 1047 DI 10.1038/nature04217 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 973AU UT WOS:000232496100049 PM 16222300 ER PT J AU Kay, J McCluskey, RT AF Kay, J McCluskey, RT TI A 60-year-old man with skin lesions and renal insufficiency - Type II cryoglobulinemia with renal disease. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID HEPATITIS-C VIRUS; SYSTEMIC-LUPUS-ERYTHEMATOSUS; MIXED CRYOGLOBULINEMIA; GLOMERULONEPHRITIS; INTERFERON; INFECTION C1 Massachusetts Gen Hosp, Rheumatol Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Kay, J (reprint author), Massachusetts Gen Hosp, Rheumatol Unit, Boston, MA 02114 USA. NR 20 TC 6 Z9 6 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 13 PY 2005 VL 353 IS 15 BP 1605 EP 1613 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 972XF UT WOS:000232486000016 PM 16221784 ER PT J AU Lim, GW Wang, SX Mao, JR AF Lim, GW Wang, SX Mao, JR TI Central glucocorticoid receptors modulate the expression of spinal cannabinoid receptors induced by chronic morphine exposure SO BRAIN RESEARCH LA English DT Article DE cannabinoid receptor; morphine; tolerance; glucocorticoid receptor ID NEUROPATHIC PAIN; RAT-BRAIN; BASOLATERAL AMYGDALA; UP-REGULATION; DORSAL HORN; ANALGESIA; MODEL; HYPERALGESIA; NEURONS; MICE AB Central cannabinoid receptors (CBRs) have been implicated in the opioid analgesic effects. However, it remains unclear as to whether the expression of central CBRs would be altered after repeated morphine exposure. Here, we show that chronic intrathecal treatment with morphine (10 mu g, twice daily or 6 days) induced a time-dependent upregulation of both CB-1 and CB-2 receptors within the spinal cord dorsal horn. This morphine-induced CB-1 and CB-2 upregulation was dose-dependently attenuated by the intrathecal co-administration of morphine with the glucocorticoid receptor (GR) antagonist RU38486 (0.25, 0.5, or 2 mu g). The intrathecal RU38486 treatment regimen also attenuated the development of morphine tolerance. These results indicate that the expression of spinal CBRs was altered following repeated morphine exposure and regulated by the activation of central GRs. (c) 2005 Elsevier B.V. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Pain Ctr, Boston, MA 02114 USA. RP Mao, JR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, MGH Pain Ctr, WACC 324,15 Parkman St, Boston, MA 02114 USA. EM jmao@partners.org FU NIDA NIH HHS [R01 DA08835]; NINDS NIH HHS [R01 NS42661, R01 NS45681] NR 61 TC 9 Z9 10 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD OCT 12 PY 2005 VL 1059 IS 1 BP 20 EP 27 DI 10.1016/j.brainres.2005.08.002 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 981DN UT WOS:000233067700004 PM 16150424 ER PT J AU Volpp, KG Konetzka, RT Zhu, JS Parsons, L Peterson, E AF Volpp, KG Konetzka, RT Zhu, JS Parsons, L Peterson, E CA National Registry Myocardial Infa TI Effect of cuts in medicare reimbursement on process and outcome of care for acute myocardial infarction patients SO CIRCULATION LA English DT Article DE delivery of health care; health policy; outcome assessment (health care) ID HOSPITAL CHARACTERISTICS; QUALITY; MORTALITY AB Background - The Balanced Budget Act ( BBA) of 1997 was designed to reduce Medicare reimbursements by $116.4 billion from 1998 to 2002. The objective of this study was to determine whether the process of care for acute myocardial infarction ( AMI) worsened to a greater degree in hospitals under increased financial strain from the BBA and whether vulnerable populations such as the uninsured were disproportionately affected. Methods and Results - We examined how process-of-care measures and in-hospital mortality for AMI patients changed in accordance with the degree of BBA-induced financial stress using data on 236 506 patients from the National Registry of Myocardial Infarction ( NRMI) and Medicare Cost Reports from 1996 to 2001. BBA-induced reductions in hospital net revenues were estimated at 1.5% ($2.9 million) for hospitals with low BBA impact and 3.2% ($ 3.7 million) for hospitals with a high impact in 1998, worsening to 2.2% ($ 4.4 million) and 4.7% ($6.0 million), respectively, by 2001. For both insured and uninsured patients in high-versus low-impact hospitals, there was no systematic worsening of time to thrombolytic therapy, balloon inflation, medication use on admission, medication use on discharge, or mortality. There was no systematic pattern of different treatment among the insured and uninsured. Operating margins decreased to a degree commensurate with the degree of revenue reduction in high-versus low-impact hospitals. Conclusions - BBA created a moderate financial strain on hospitals. However, process-of-care measures for both insured and uninsured patients with AMI were not appreciably affected by these revenue reductions. It is important to note that these results apply only to AMI patients; we do not know the degree to which these findings generalize to other conditions. C1 Univ Penn, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Univ Penn, Wharton Sch, Philadelphia, PA 19104 USA. Univ Chicago, Chicago, IL 60637 USA. Ovat Res Grp, Seattle, WA USA. Duke Univ, Durham, NC USA. RP Volpp, KG (reprint author), 1232 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM volpp70@wharton.upenn.edu NR 23 TC 32 Z9 32 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 11 PY 2005 VL 112 IS 15 BP 2268 EP 2275 DI 10.1161/CIRCULATIONAHA.105.534164 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 972SJ UT WOS:000232473200009 PM 16203913 ER PT J AU Larose, E Yeghiazarians, Y Libby, P Yucel, EK Aikawa, M Kacher, DF Aikawa, E Kinlay, S Schoen, FJ Selwyn, AP Ganz, P AF Larose, E Yeghiazarians, Y Libby, P Yucel, EK Aikawa, M Kacher, DF Aikawa, E Kinlay, S Schoen, FJ Selwyn, AP Ganz, P TI Characterization of human atherosclerotic plaques by intravascular magnetic resonance imaging SO CIRCULATION LA English DT Article DE atherosclerosis; intravascular ultrasound; magnetic resonance imaging ID CORONARY-ARTERY INJURY; IN-VIVO; MRI; STABILIZATION; INFLAMMATION; ANGIOGRAPHY; ULTRASOUND; COMPONENTS; THROMBOSIS; BIOLOGY AB Background - Development and validation of novel imaging modalities to assess the composition of human atherosclerotic plaques will improve the understanding of atheroma evolution and could facilitate evaluation of therapeutic strategies for plaque modification. Surface MRI can characterize tissue content of carotid but not deeper arteries. This study evaluated the usefulness of intravascular MRI ( IVMRI) to discern the composition of human iliac arteries in vivo. Methods and Results - Initial studies validated IVMRI against histopathology of human atherosclerotic arteries ex vivo. A 0.030- inch- diameter IVMRI detector coil was advanced into isolated human aortoiliac arteries and coupled to a 1.5-T scanner. Information from combined T1-, moderate T2-, and proton- density - weighted images differentiated lipid, fibrous, and calcified components with favorable sensitivity and specificity and allowed accurate quantification of plaque size. The validated approach was then applied to image iliac arteries of 25 human subjects in vivo, and results were compared with those of intravascular ultrasound (IVUS). IVMRI readily visualized inner and outer plaque boundaries in all arteries, even those with extensive calcification that precluded IVUS interpretation. It also revealed the expected heterogeneity of atherosclerotic plaque content that was noted during ex vivo validation. Again, IVUS did not disclose this heterogeneity. The level of interobserver and intraobserver agreement in the interpretation of plaque composition was high for IVMRI but poor for IVUS. Conclusions - IVMRI can reliably identify plaque composition and size in arteries deep within the body. Identification of plaque components by IVMRI in vivo has important implications for the understanding and modification of human atherosclerosis. C1 Brigham & Womens Hosp, Div Cardiovasc, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. VA Boston Healthcare Syst, W Roxbury, MA USA. RP Ganz, P (reprint author), Brigham & Womens Hosp, Div Cardiovasc, Dept Med, 75 Francis St, Boston, MA 02115 USA. EM pganz@aol.com FU NHLBI NIH HHS [HL-56985, P01-HL-48743] NR 27 TC 69 Z9 71 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 11 PY 2005 VL 112 IS 15 BP 2324 EP 2331 DI 10.1161/CIRCULATIONAHA.105.538942 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 972SJ UT WOS:000232473200016 PM 16203910 ER PT J AU Masland, RH AF Masland, RH TI Sensory systems: Fine-tuning the visual scene SO CURRENT BIOLOGY LA English DT Editorial Material ID RETINA AB The visual system adjusts its properties for efficient representation of the objects present in the environment at the time. A new report suggests that complex processing of this sort can begin as early as the retina itself, but some important issues remain unresolved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. RP Masland, RH (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. EM masland@helix.mgh.harvard.edu NR 6 TC 3 Z9 3 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD OCT 11 PY 2005 VL 15 IS 19 BP R808 EP R810 DI 10.1016/j.cub.2005.09.023 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 976QK UT WOS:000232748100017 PM 16213814 ER PT J AU Knake, S Triantafyllou, C Wald, LL Wiggins, G Kirk, GP Larsson, PG Stufflebeam, SM Foley, MT Shiraishi, H Dale, AM Halgren, E Grant, PE AF Knake, S Triantafyllou, C Wald, LL Wiggins, G Kirk, GP Larsson, PG Stufflebeam, SM Foley, MT Shiraishi, H Dale, AM Halgren, E Grant, PE TI 3T phased array MRI improves the presurgical evaluation in focal epilepsies - A prospective study SO NEUROLOGY LA English DT Article ID CORTICAL DYSPLASIA; SURGERY AB Background: Although detection of concordant lesions on MRI significantly improves postsurgical outcomes in focal epilepsy (FE), many conventional MR studies remain negative. The authors evaluated the role of phased array surface coil studies performed at 3 Tesla (3T PA MRI). Methods: Forty patients with medically intractable focal epilepsies were prospectively imaged with 3T PA-MRI including high matrix TSE T2, fluid attenuated inversion recovery, and magnetization prepared rapid gradient echo. All patients were considered candidates for epilepsy surgery. 3T PA-MRIs were reviewed by a neuroradiologist experienced in epilepsy imaging with access to clinical information. Findings were compared to reports of prior standard 1.5T MRI epilepsy studies performed at tertiary care centers. Results: Experienced, unblinded review of 3T PA-MRI studies yielded additional diagnostic information in 48% (19/40) compared to routine clinical reads at 1.5T. In 37.5% (15/40), this additional information motivated a change in clinical management. In the subgroup of patients with prior 1.5T MRIs interpreted as normal, 3T PA-MRI resulted in the detection of a new lesion in 65% (15/23). In the subgroup of 15 patients with known lesions, 3T PA-MRI better defined the lesion in 33% (5/15). Conclusion: Phased array surface coil studies performed at 3 Tesla read by an experienced unblinded neuroradiologist can improve the presurgical evaluation of patients with focal epilepsy when compared to routine clinical 1.5T studies read at tertiary care centers. C1 Massachusetts Gen Hosp, Neuroradiol Sect, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, AA Martinos Ctr Biomed Imaging, Charlestown, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA USA. Univ Marburg, Dept Neurol, Marburg, Germany. Natl Ctr Epilepsy, Sandvika, Norway. RP Grant, PE (reprint author), Massachusetts Gen Hosp, Neuroradiol Sect, Dept Radiol, Gray 2,B285,55 Fruit St, Boston, MA 02114 USA. EM ellen@nmr.mgh.harvard.edu RI Dale, Anders/A-5180-2010; Triantafyllou, Christina/E-7724-2011; Shiraishi, Hideaki/A-8427-2012; Wald, Lawrence/D-4151-2009 FU NCRR NIH HHS [P41 RR014075, P41RR14075] NR 20 TC 98 Z9 101 U1 0 U2 6 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 1026 EP 1031 DI 10.1212/01.wnl.0000179355.04481.3c PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 972RF UT WOS:000232470200012 PM 16217054 ER PT J AU Li, G Shofer, JB Kukull, WA Peskind, ER Tsuang, DW Breitner, JCS McCormick, W Bowen, JD Teri, L Schellenberg, GD Larson, EB AF Li, G Shofer, JB Kukull, WA Peskind, ER Tsuang, DW Breitner, JCS McCormick, W Bowen, JD Teri, L Schellenberg, GD Larson, EB TI Serum cholesterol and risk of Alzheimer disease - A community-based cohort study SO NEUROLOGY LA English DT Article ID APOLIPOPROTEIN-E POLYMORPHISM; TRANSGENIC MOUSE MODEL; CORONARY HEART-DISEASE; VASCULAR DEMENTIA; LATE-LIFE; AMYLOID PATHOLOGY; CONTROLLED TRIAL; PLASMA-LIPIDS; LIPOPROTEINS; ALLELE AB Objectives: To examine the association of serum total cholesterol (TC) and high density lipoprotein (HDL) levels and subsequent incidence of dementia and Alzheimer disease (AD) in a population-based cohort study. Methods: A cohort of cognitively intact persons, aged 65 and older, was randomly selected from Group Health Cooperative (GHC), a large health maintenance organization, and was assessed biennially for dementia. Premorbid levels of TC and HDL were obtained from a computerized clinical laboratory database at GHC. Cox proportional hazards regression was used to calculate hazard ratios (HR, 95% CI) for dementia and AD associated with quartiles of TC and HDL levels. Results: Of the 2,356 eligible participants, 2,141 had at least one serum TC measure prior to the initial enrollment. Using the lowest TC quartiles as the reference group, the HR in the highest TC quartiles was not significantly elevated for dementia (1.16, 0.81 to 1.67) or for AD (1.00, 0.61 to 1.62) after adjusting for age, sex, education, baseline cognition, vascular comorbidities, body mass index, and lipid-lowering agent use. Serum HDL showed a similar lack of significant association with risk of dementia or AD. Models that included the presence of one or more APOE-epsilon 4 alleles showed a typical association of epsilon 4 with AD risk. This association was not materially modified by inclusion of TC level. Conclusion: The data do not support an association between serum total cholesterol or high density lipoprotein in late life and subsequent risk of dementia or Alzheimer disease (AD). The increased risk of AD with APOE-epsilon 4 is probably not mediated by serum total cholesterol levels. C1 VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Mental Illness Res & Educ Clin Ctr, Seattle, WA 98108 USA. Ctr Hlth Studies, Grp Hlth Cooperat, Seattle, WA USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. Univ Washington, Dept Neurol, Seattle, WA 98195 USA. Univ Washington, Dept Psychosocial & Community Hlth, Seattle, WA 98195 USA. Univ Washington, Dept Geriatr & Gerontol, Seattle, WA 98195 USA. RP Li, G (reprint author), VA Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, 1660 S Columbian Way,Mailstop S-116 MIRECC, Seattle, WA 98108 USA. EM gli@u.washington.edu RI Tsuang, Debby/L-7234-2016; OI Tsuang, Debby/0000-0002-4716-1894; Kukull, Walter/0000-0001-8761-9014 FU NIA NIH HHS [AG16976, AG05136, AG06781, AG20020] NR 47 TC 77 Z9 80 U1 2 U2 8 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 1045 EP 1050 DI 10.1212/01.wnl.0000178989.87072.11 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 972RF UT WOS:000232470200015 PM 16217057 ER PT J AU Cochrane, T Schmahmann, JD AF Cochrane, T Schmahmann, JD TI Compressive myelopathy presenting as cervical cord neurapraxia: A differential diagnosis of TIA SO NEUROLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Schmahmann, JD (reprint author), Massachusetts Gen Hosp, Dept Neurol, CPZS 340,Fruit St, Boston, MA 02114 USA. EM jschmahmann@partners.org NR 7 TC 2 Z9 2 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD OCT 11 PY 2005 VL 65 IS 7 BP 1140 EP 1141 DI 10.1212/01.wnl.0000178892.89896.c1 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 972RF UT WOS:000232470200044 PM 16217082 ER PT J AU Karnik, SK Hughes, CM Gu, XY Rozenblatt-Rosen, O McLean, GW Xiong, Y Meyerson, M Kim, SK AF Karnik, SK Hughes, CM Gu, XY Rozenblatt-Rosen, O McLean, GW Xiong, Y Meyerson, M Kim, SK TI Menin regulates pancreatic islet growth by promoting histone methylation and expression of genes encoding p27(Kip1) and p18(INK4c) SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE islet of Langerhans; Men1; multiple endocrine neoplasia; tumor suppressor; diabetes mellitus ID MULTIPLE ENDOCRINE NEOPLASIA; KINASE INHIBITOR P18(INK4C); METHYLTRANSFERASE COMPLEX; CONDITIONAL INACTIVATION; PITUITARY TUMORIGENESIS; MICE LACKING; TRANSCRIPTION; TYPE-1; HYPERPLASIA; PROTEIN AB Menin, the product of the Men1 gene mutated in familial multiple endocrine neoplasia type 1 (MEN1), regulates transcription in differentiated cells. Menin associates with and modulates the histone methyltransferase activity of a nuclear protein complex to activate gene expression. However, menin-dependent histone methyltransferase activity in endocrine cells has not been demonstrated, and the mechanism of endocrine tumor suppression by menin remains unclear. Here, we show that menin-dependent histone methylation maintains the in vivo expression of cyclin-dependent kinase (CDK) inhibitors to prevent pancreatic islet tumors. In vivo expression of CDK inhibitors, including p27 and p18, and other cell cycle regulators is disrupted in mouse islet tumors lacking menin. Chromatin immunoprecipitation studies reveal that menin directly associates with regions of the p27 and p18 promoters and increases methylation of lysine 4 (Lys-4) in histone H3 associated with these promoters. Moreover, H3 Lys-4 methylation associated with p27 and p18 is reduced in islet tumors from Men 1 mutant mice. Thus, H3 Lys-4 methylation is a crucial function of menin in islet tumor suppression. These studies suggest an epigenetic mechanism of tumor suppression: by promoting histone modifications, menin maintains transcription at multiple loci encoding cell cycle regulators essential for endocrine growth control. C1 Stanford Univ, Dept Dev Biol, Sch Med, Stanford, CA 94305 USA. Stanford Univ, Dept Med, Sch Med, Div Oncol, Stanford, CA 94305 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Univ N Carolina, Dept Biochem & Biophys, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. Univ N Carolina, Program Mol Biol & Biotechnol, Chapel Hill, NC 27599 USA. RP Kim, SK (reprint author), Stanford Univ, Dept Dev Biol, Sch Med, Stanford, CA 94305 USA. EM seungkim@cmgm.stanford.edu RI Meyerson, Matthew/E-7123-2012 NR 42 TC 228 Z9 238 U1 1 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 14659 EP 14664 DI 10.1073/pnas.0503484102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 974PJ UT WOS:000232603600034 PM 16195383 ER PT J AU Ly, NP Komatsuzaki, K Fraser, IP Tseng, AA Prodhan, P Moore, KJ Kinane, TB AF Ly, NP Komatsuzaki, K Fraser, IP Tseng, AA Prodhan, P Moore, KJ Kinane, TB TI Netrin-1 inhibits leukocyte migration in vitro and in vivo SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE chemotaxis; inflammation; guidance cue ID GROWTH-CONE ATTRACTION; RECEPTORS; REPULSION; LUNG; MORPHOGENESIS; CHEMOTAXIS; MODULATION; GUIDANCE; UNC5H2; CELLS AB Cell migration plays important roles in embryonic development and inflammation, and this process is highly regulated to ensure tissue homeostasis. A number of barriers exist to prevent the inappropriate migration of leukocytes into healthy peripheral tissues, including retention of these cells in the inactive state and maintenance of the integrity and charge of the vascular endothelium. However, active signals also are likely to exist that can repulse cells or abolish existing cell migration. One such paradigm exists in the developing nervous system, where neuronal migration is mediated by a balance between chemoattractive and chemorepulsive signals. The ability of the guidance molecule netrin-1 to repulse or abolish attraction of neuronal cells expressing the UNC5b receptor makes it an attractive candidate for the regulation of inflammatory cell migration. Here, we show that netrin-1 is expressed on vascular endothelium, where it is regulated by infection and inflammatory cytokines. The netrin-1 receptor UNC5b is strongly expressed by leukocytes, upon which netrin-1 acts as a potent inhibitor of migration to different chemotactic stimuli both in vivo and in vitro. These data suggest that endothelial expression of netrin-1 may inhibit basal cell migration into tissues and that its down-regulation with the onset of sepsis/inflammation may facilitate leukocyte recruitment. C1 Harvard Univ, Sch Med,Massachusetts Gen Hosp, Lab Dev Immunol, Dept Pediat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Lipid Metab Unit, Boston, MA 02114 USA. RP Kinane, TB (reprint author), Harvard Univ, Sch Med,Massachusetts Gen Hosp, Lab Dev Immunol, Dept Pediat, 55 Fruit St, Boston, MA 02114 USA. EM tkinane@partners.org OI Moore, kathryn/0000-0003-2505-2547 FU NHLBI NIH HHS [501 HL 58819-04]; NIA NIH HHS [AG20255, R01 AG020255] NR 22 TC 125 Z9 130 U1 1 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 11 PY 2005 VL 102 IS 41 BP 14729 EP 14734 DI 10.1073/pnas.0506233102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 974PJ UT WOS:000232603600046 PM 16203981 ER PT J AU Chen, ZB Benoist, C Mathis, D AF Chen, ZB Benoist, C Mathis, D TI How defects in central tolerance impinge on a deficiency in regulatory T cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE Aire; Foxp3; central tolerance; peripheral regulation; autoimmunity ID IMMUNOLOGICAL SELF-TOLERANCE; TRANSCRIPTION FACTOR FOXP3; NOD MOUSE; AUTOIMMUNE-DISEASE; IMMUNE DYSREGULATION; MULTIPLE-SCLEROSIS; NEGATIVE SELECTION; SCURFY MOUSE; GENE; PROTEIN AB Both central (thymic) and peripheral (nonthymic) mechanisms are important for the induction and maintenance of T cell tolerance. Mice with a defect in Foxp3, required for the generation and activity of CD4(+)CD25(+) regulatory T cells, exhibit massive lymphoproliferation and severe inflammatory infiltration of multiple organs, in particular the lungs, liver, and skin. We have explored how this phenotype is influenced by an additional defect in central tolerance induction, generated by either crossing in a null mutation of the Aire gene or substituting the nonobese diabetic (NOD) genetic background. The double-deficient mice had fulminant autoimmunity in very early life and a gravely shortened lifespan vis-a-vis single-deficient littermates. They showed massive lymphoproliferation and exacerbated inflammatory damage, particularly in the lungs and liver. Yet, the range of affected sites was not noticeably extended, and, surprisingly, many organs, or regions of organs, remained untouched, suggesting additional important mechanisms to enforce immunological self-tolerance. C1 Joslin Diabet Ctr, Sect Immunol & Immunogenet, Boston, MA 02215 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02215 USA. RP Benoist, C (reprint author), Joslin Diabet Ctr, Sect Immunol & Immunogenet, 1 Joslin Pl, Boston, MA 02215 USA. EM cbdm@joslin.harvard.edu FU NIDDK NIH HHS [1R01DK60027, R01 DK060027] NR 45 TC 79 Z9 85 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 11 PY 2005 VL 102 IS 41 BP 14735 EP 14740 DI 10.1073/pnas.0507014102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 974PJ UT WOS:000232603600047 PM 16203996 ER PT J AU Morrell, KC Hodge, WA Krebs, DE Mann, RW AF Morrell, KC Hodge, WA Krebs, DE Mann, RW TI Corroboration of in vivo cartilage pressures with implications for synovial joint tribology and osteoarthritis causation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HUMAN HIP-JOINT; ACETABULAR CONTACT PRESSURES; ARTICULAR-CARTILAGE; UNCONFINED COMPRESSION; MEASURING INVITRO; REHABILITATION; LUBRICATION; INVIVO; VITRO; PRESSURIZATION AB Pressures on normal human acetabular cartilage have been collected from two implanted instrumented femoral head hemiprostheses. Despite significant differences in subjects' gender, morphology, mobility, and coordination, in vivo pressure measurements from both subjects covered similar ranges, with maximums of 5-6 MPa in gait, and as high as 18 MPa in other movements. Normalized for subject weight and height (nMPa), for free-speed walking the maximum pressure values were 25.2 for the female subject and 24.5 for the male subject. The overall maximum nMPa values were 76.2 for the female subject during rising from a chair at 11 months postoperative and 82.3 for the male subject while descending steps at 9 months postoperative. These unique in vivo data are consistent with corresponding cadaver experiments and model analyses. The collective results, in vitro data, model studies, and now corroborating in vivo data support the self-pressurizing "weeping" theory of synovial joint lubrication and provide unique information to evaluate the influence of in vivo pressure regimes on osteoarthritis causation and the efficacy of augmentations to, and substitutions for, natural cartilage. C1 MIT, Dept Engn Mech, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Inst Hlth Profess, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Orthoped Surg, Boston, MA 02114 USA. RP Mann, RW (reprint author), MIT, Dept Engn Mech, Room 3-137D, Cambridge, MA 02139 USA. EM rwmann@mit.edu FU NIAMS NIH HHS [AR40036]; NICHD NIH HHS [HD30063] NR 58 TC 43 Z9 44 U1 0 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 11 PY 2005 VL 102 IS 41 BP 14819 EP 14824 DI 10.1073/pnas.0507117102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 974PJ UT WOS:000232603600061 PM 16203974 ER PT J AU Stamm, LM Pak, MA Morisaki, JH Snapper, SB Rottner, K Lommel, S Brown, EJ AF Stamm, LM Pak, MA Morisaki, JH Snapper, SB Rottner, K Lommel, S Brown, EJ TI Role of the WASP family proteins for Mycobacterium marinum actin tail formation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE mycobacteria; neuronal Wiskott-Aldrich syndrome protein; infection; bacterial motility ID ALDRICH-SYNDROME PROTEIN; ENTEROPATHOGENIC ESCHERICHIA-COLI; N-WASP; ARP2/3 COMPLEX; PEDESTAL FORMATION; PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE; BURKHOLDERIA-PSEUDOMALLEI; INTRACELLULAR SURVIVAL; SHIGELLA-FLEXNERI; VACCINIA VIRUS AB Mycobacterium marinum, a natural pathogen of fish and frogs and an occasional pathogen of humans, is capable of inducing actin tail formation within the cytoplasm of macrophages, leading to actin-based motility and intercellular spread. Actin tail formation by M. marinum is markedly reduced in macrophages deficient in the Wiskott-Aldrich syndrome protein (WASP), which still contain the closely related and ubiquitously expressed protein N-WASP (neuronal WASP). In fibroblasts lacking both WASP and N-WASP, M. marinum is incapable of efficient actin polymerization and of intercellular spread. By reconstituting these cells, we find that M. marinum is able to use either WASP or N-WASP to induce actin polymerization. Inhibition or genetic deletion of tyrosine phosphorylation, Nck, WASP-interacting protein, and Cdc42 does not affect M. marinum actin tail formation, excluding the participation of these molecules as upstream activators of N-WASP in the initiation of actin-based motility. In contrast, deletion of the phosphatidylinositol 4,5-bisphosphate-binding basic motif in N-WASP eliminates M. marinum actin tail formation. Together, these data demonstrate that M. marinum subversion of host actin polymerization is most similar to distantly related Gram-negative organisms but that its mechanism for activating WASP family proteins is unique. C1 Univ Calif San Francisco, Program Microbial Pathogenesis & Host Def, San Francisco, CA 94143 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. German Res Ctr Biotechnol, Cytoskeleton Dynam Grp, D-38124 Braunschweig, Germany. German Res Ctr Biotechnol, Dept Cell Biol, D-38124 Braunschweig, Germany. RP Brown, EJ (reprint author), Univ Calif San Francisco, Program Microbial Pathogenesis & Host Def, San Francisco, CA 94143 USA. EM ebrown@medicine.ucsf.edu OI Rottner, Klemens/0000-0003-4244-4198 FU NIAID NIH HHS [AI55614, R01 AI055614] NR 43 TC 40 Z9 41 U1 0 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 11 PY 2005 VL 102 IS 41 BP 14837 EP 14842 DI 10.1073/pnas.0504663102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 974PJ UT WOS:000232603600064 PM 16199520 ER PT J AU Blumberg, MS Seelke, AMH Lowen, SB Karlsson, KAE AF Blumberg, MS Seelke, AMH Lowen, SB Karlsson, KAE TI Dynamics of sleep-wake cyclicity in developing rats SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE atonia; renewal process; Markov process; development ID FRACTAL RENEWAL PROCESSES; INFANT RATS; REM-SLEEP; TRANSITIONS; ATONIA; ORGANIZATION; MODEL; EEG AB Adult mammals cycle between periods of sleep and wakefulness. Recent assessments of these cycles in humans and other mammals [Lo, C. C., Amaral, L. A. N., Havlin, S., Ivanov, P. Ch., Penzel, T., Peter, J.H. & Stanley, H. E. (2002) Europhys. Lett. 57,625-631 and Lo, C. C., Chou, T., Penzel, T., Scammell, T. E., Strecker, R. E., Stanley, H. E. & Ivanov, P. Ch. (2004) Proc. Natl. Acad. Sci. 101, 17545-17548] indicate that sleep bout durations exhibit an exponential distribution, whereas wake bout durations exhibit a power-law distribution. Moreover, it was found that wake bout distributions, but not sleep bout distributions, exhibit scale invariance across mammals of different body sizes. Here we test the generalizability of these findings by examining the distributions of sleep and wake bout durations in infant rats between 2 and 21 days of age. In agreement with Lo et al., we find that sleep bout durations exhibit exponential distributions at all ages examined. In contrast, however, wake bout durations also exhibit exponential distributions at the younger ages, with a clear power-law distribution only emerging at the older ages. Further analyses failed to find substantial evidence either of short- or long-term correlations in the data, thus suggesting that the durations of current sleep and wake bouts evolve through time without memory of the durations of preceding bouts. These findings further support the notion that bouts of sleep and wakefulness are regulated independently. Moreover, in light of recent evidence that developmental changes in sleep and wake bouts can be attributed in part to increasing forebrain influences, these findings suggest the possibility of identifying specific neural circuits that modulate the changing complexity of sleep and wake dynamics during development. C1 Univ Iowa, Dept Psychol, Program Behav & Cognit Neurosci, Iowa City, IA 52242 USA. Harvard Univ, Sch Med, Dept Psychiat, McLean Hosp, Belmont, MA 02478 USA. Vet Adm Greater Los Angeles Healthcare Syst, Sepulveda Ambulatory Care Ctr, Neurobiol Res Unit 15A3, North Hills, CA 94313 USA. RP Blumberg, MS (reprint author), Univ Iowa, Dept Psychol, Program Behav & Cognit Neurosci, E11 Seashore Hall, Iowa City, IA 52242 USA. EM mark-blumberg@uiowa.edu OI Blumberg, Mark/0000-0001-6969-2955 FU NIMH NIH HHS [MH50701, K02 MH066424, MH66424, R01 MH050701, R29 MH050701] NR 23 TC 77 Z9 78 U1 0 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 11 PY 2005 VL 102 IS 41 BP 14860 EP 14864 DI 10.1073/pnas.0506340102 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 974PJ UT WOS:000232603600068 PM 16192355 ER PT J AU Aguiar, RCT Takeyama, K He, CY Kreinbrink, K Shipp, MA AF Aguiar, RCT Takeyama, K He, CY Kreinbrink, K Shipp, MA TI B-aggressive lymphoma family proteins have unique domains that modulate transcription and exhibit poly(ADP-ribose) polymerase activity SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID INACTIVE X-CHROMOSOME; CRYSTAL-STRUCTURES; HISTONE MACROH2A; CORE HISTONE; BINDING; CELLS; GENE; PARP; IDENTIFICATION; COREPRESSOR AB BAL1 (B-aggressive lymphoma 1) was originally identified as a risk- related gene in diffuse large B-cell lymphoma. BAL1 encodes a nuclear protein with N-terminal macro domains and a putative C-terminal poly( ADP-ribose) polymerase ( PARP) active site. Macro domains are sequences homologous to the non-histone region of histone macroH2A. Several lines of evidence suggest that these domains may modulate transcription, including a high concentration of histone macroH2A in the inactive X chromosome, direct interference with transcription factor binding in a positioned nucleosome, and structural similarity to DNA binding domains. Poly( ADP-ribosyl) ation is a critical post-translational modification that regulates chromatin configuration and transcription. In this report we describe two additional BAL family members, BAL2 and BAL3, with N-terminal macro domains and putative C-terminal PARP active sites and assess the function of these specific regions in BAL family members. Herein, we demonstrate that BAL macro domains repress transcription when tethered to a promoter. In addition, we show that BAL2 and BAL3, but not BAL1, exhibit PARP activity. In agreement with these data, BAL1 lacks several critical donor and acceptor residues that are conserved in the BAL2 and -3 PARP active sites. Of interest, BAL family members with inactive or functional PARP domains differed in their ability to repress transcription. BAL family members are the only described proteins with both PARP and macro domains, underscoring the potential functional significance of this unique combination. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Div Hematol Malignancies, Boston, MA 02115 USA. RP Shipp, MA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Div Hematol Malignancies, 44 Binney St,Rm M513, Boston, MA 02115 USA. EM margaret_shipp@dfci.harvard.edu NR 35 TC 86 Z9 88 U1 1 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 7 PY 2005 VL 280 IS 40 BP 33756 EP 33765 DI 10.1074/jbc.M505408200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 969JF UT WOS:000232229700011 PM 16061477 ER PT J AU Berbeco, RI Mostafavi, H Sharp, GC Jiang, SB AF Berbeco, RI Mostafavi, H Sharp, GC Jiang, SB TI Towards fluoroscopic respiratory gating for lung tumours without radiopaque markers SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article AB Due to the risk of pneumothorax, many clinicians are reluctant to implant radiopaque markers within patients' lungs for the purpose of radiographic or fluoroscopic tumour localization. We propose a method of gated therapy using fluoroscopic information without the implantation of radiopaque markers. The method presented here does not rely on any external motion signal either. Breathing phase information is found by analysing the fluoroscopic intensity fluctuations in the lung. As the lungs fill/empty, the radiological pathlength through them shortens/lengthens, giving brighter/darker fluoroscopic intensities. The phase information is combined with motion-enhanced template matching to turn the beam on when the tumour is in the desired location. A study based on patient data is presented to demonstrate the feasibility of this procedure. The resulting beam-on pattern is similar to that produced by an external gating system. The only discrepancies occur briefly and at the gate edges. C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Varian Med Syst Inc, Ginzton Technol Ctr, Palo Alto, CA USA. RP Berbeco, RI (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. EM rberbeco@partners.org NR 43 TC 94 Z9 96 U1 0 U2 5 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD OCT 7 PY 2005 VL 50 IS 19 BP 4481 EP 4490 DI 10.1088/0031-9155/50/19/004 PG 10 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 980VX UT WOS:000233047400004 PM 16177484 ER PT J AU Zhang, YH Brooks, DH Boas, DA AF Zhang, YH Brooks, DH Boas, DA TI A haemodynamic response function model in spatio-temporal diffuse optical tomography SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article AB Diffuse optical tomography (DOT) is a new and effective technique for functional brain imaging. It can detect local changes in both oxygenated and deoxygenated haemoglobin concentrations in tissue based on differential absorption at multiple wavelengths. Traditional methods in spatio-temporal analysis of haemoglobin concentrations in diffuse optical tomography first reconstruct the spatial distribution at different time instants independently, then look at the temporal dynamics on each pixel, without incorporating any temporal information as a prior in the image reconstruction. In this work, we present a temporal haemodynamic response function model described by a basis function expansion, in a joint spatio-temporal DOT reconstruction of haemoglobin concentration changes during simulated brain activation. In this joint framework, we simultaneously employ spatial regularization, spectral information and temporal assumptions. We also present an efficient algorithm for solving the associated large-scale systems. The expected improvements in spatial resolution and contrast-to-noise ratio are illustrated with simulations of human brain activation. C1 Univ Michigan Hosp, Dept Radiol, Ann Arbor, MI 48109 USA. Northeastern Univ, Dept Elect & Comp Engn, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr, Charlestown, MA 02129 USA. RP Zhang, YH (reprint author), Univ Michigan Hosp, Dept Radiol, 1500 E Med Ctr Dr,CGC B2109, Ann Arbor, MI 48109 USA. EM yihzhang@med.umich.edu FU NCRR NIH HHS [P41-RR14075]; NIBIB NIH HHS [R01-EB002482] NR 45 TC 30 Z9 30 U1 0 U2 0 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD OCT 7 PY 2005 VL 50 IS 19 BP 4625 EP 4644 DI 10.1088/0031-9155/50/19/014 PG 20 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 980VX UT WOS:000233047400014 PM 16177494 ER PT J AU Sharp, GC Kollipara, S Madden, T Jiang, SB Rosenthal, SJ AF Sharp, GC Kollipara, S Madden, T Jiang, SB Rosenthal, SJ TI Anatomic feature-based registration for patient set-up in head and neck cancer radiotherapy SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID DIGITALLY RECONSTRUCTED RADIOGRAPHS; PORTAL IMAGE REGISTRATION; RADIATION-THERAPY; ALGORITHM; VERIFICATION; DIMENSIONS; INSPECTION; ROTATIONS; ALIGNMENT; PROSTATE AB Modem radiotherapy equipment is capable of delivering high precision conformal dose distributions relative to isocentre. One of the barriers to precise treatments is accurate patient re-positioning before each fraction of treatment. At Massachusetts General Hospital, we perform daily patient alignment using radiographs, which are captured by flat panel imaging devices and sent to an analysis program. A trained therapist manually selects anatomically significant features in the skeleton, and couch movement is computed based on the image coordinates of the features. The current procedure takes about 5 to 10 min and significantly affects the efficiency requirement in a busy clinic. This work presents our effort to develop an improved, semi-automatic procedure that uses the manually selected features from the first treatment fraction to automatically locate the same features on the second and subsequent fractions. An implementation of this semi-automatic procedure is currently in clinical use for head and neck tumour sites. Radiographs collected from 5 10 patient set-UPS were used to test this algorithm. A mean difference of 1.5 mm between manual and automatic localization of individual features and a mean difference of 0.8 mm for overall set-up were seen. C1 Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Sharp, GC (reprint author), Harvard Univ, Sch Med, Boston, MA 02114 USA. EM gcsharp@partners.org FU NCI NIH HHS [5 P01 CA21239-24] NR 34 TC 13 Z9 14 U1 3 U2 3 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD OCT 7 PY 2005 VL 50 IS 19 BP 4667 EP 4679 DI 10.1088/0031-9155/50/19/016 PG 13 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 980VX UT WOS:000233047400016 PM 16177496 ER PT J AU Lee, ST Chu, K Jung, KH Ko, SY Kim, EH Sinn, DI Lee, YS Lo, EH Kim, M Roh, JK AF Lee, ST Chu, K Jung, KH Ko, SY Kim, EH Sinn, DI Lee, YS Lo, EH Kim, M Roh, JK TI Granulocyte colony-stimulating factor enhances anglogenesis after focal cerebral ischemia SO BRAIN RESEARCH LA English DT Article DE granulocyte-colony stimulating factor (G-CSF); cerebral ischemia; angiogenesis; time window; eNOS ID BLOOD-BRAIN-BARRIER; ENDOTHELIAL PROGENITOR CELLS; BONE-MARROW; INTRACEREBRAL HEMORRHAGE; FUNCTIONAL RECOVERY; ARTERY OCCLUSION; STEM-CELLS; ANGIOGENESIS; RATS; STROKE AB Granulocyte colony-stimulating factor (G-CSF) is a neuroprotective agent and activates endothelial proliferation and bone marrow stem cell mobilization. We studied the effect of G-CSF on angiogenesis and neurological recovery after focal cerebral ischemia. After the induction of transient focal ischemia in rats, G-CSF (50 mu g/kg/day, i.p.) or PBS was administered for 3 days. We evaluated the functional recovery, infarct volume, inflammatory infiltration, blood-brain barrier (131313) disruption, hemispheric atrophy, protein expressions of endothelial nitric oxide synthase (eNOS) and angiopoietins, and the therapeutic time window of G-CSF administration. We then analyzed enclothelial cell proliferation, the vascular surface area, the number of branch points, and the vascular length. G-CSF treatment improved behavioral recovery and reduced the infarct volume, the inflammatory infiltration, the 131313 disruption, and the hemispheric atrophy. G-CSF injection, starting at 2 h, I day, or 4 days after ischemia, resulted in a better functional recovery and a greater reduction in hemispheric atrophy than injection starting at day 7. The vascular surface area, the vascular branch points, the vascular length, the number of BrdU(+) endothelial cells, and eNOS/ angiopoietin-2 expression were significantly increased in the G-CSF group compared with the ischemia-only group. G-CSF injection starting at I day induced larger endothelial proliferation compared with injection starting at 7 days. In this study, we provide evidences that G-CSF enhances the angiogenesis and reduces the ischemic damage, which promotes the long-term functional recovery. (c) 2005 Elsevier B.V. All rights reserved. C1 Seoul Natl Univ Hosp, Dept Neurol, Stem Cell Res Ctr, Clin Res Inst,Stroke & Neural Stem Cell Lab, Seoul 110744, South Korea. Seoul Natl Univ, Program Neurosci, Neurosci Res Inst, SNUMRC, Seoul 110744, South Korea. Seoul Natl Hosp, Ctr Alcohol & Drug Addict Res, Seoul, South Korea. Korea Ctr Dis Control & Prevent, Div Epidem Intelligence Serv, Seoul, South Korea. Seoul Natl Univ, Seoul Municipal Boramae Hosp, Dept Neurol, Seoul, South Korea. Massachusetts Gen Hosp, Dept Neurol, Neuroprotect Res Lab, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Radiol, Neuroprotect Res Lab, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Neurosci Program, Charlestown, MA 02129 USA. Seoul Natl Univ, Brain Korea 21 Project Med Sci, Seoul, South Korea. RP Roh, JK (reprint author), Seoul Natl Univ Hosp, Dept Neurol, Stem Cell Res Ctr, Clin Res Inst,Stroke & Neural Stem Cell Lab, 28,Yongondong, Seoul 110744, South Korea. EM rohjk@snu.ac.kr RI Kim, Manho/J-2738-2012; Roh, Jae Kyu/J-5459-2012; Lee, Soon-Tae/C-4663-2013; Lee, Yong Seok/J-5587-2012 NR 27 TC 108 Z9 129 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD OCT 5 PY 2005 VL 1058 IS 1-2 BP 120 EP 128 DI 10.1016/j.brainres.2005.07.076 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 978JF UT WOS:000232868700013 PM 16150422 ER PT J AU Schon, K Atri, A Hasselmo, ME Tricarico, MD LoPresti, ML Stern, CE AF Schon, K Atri, A Hasselmo, ME Tricarico, MD LoPresti, ML Stern, CE TI Scopolamine reduces persistent activity related to long-term encoding in the parahippocampal gyrus during delayed matching in humans SO JOURNAL OF NEUROSCIENCE LA English DT Article DE memory formation; cholinergic; fMRI; medial temporal lobe; delayed match to sample; computational modeling ID SPATIAL WORKING-MEMORY; MEDIAL TEMPORAL-LOBE; VISUAL RECOGNITION MEMORY; EVENT-RELATED FMRI; CHOLINERGIC ENHANCEMENT; ENTORHINAL CORTEX; RHESUS-MONKEYS; BRAIN ACTIVITY; PERIRHINAL CORTEX; SUBSEQUENT MEMORY AB Recent computational modeling and slice physiology studies have suggested that long- term encoding may depend on sustained spiking during brief memory delays in parahippocampal neurons, and that this persistent spiking activity is modulated by effects of acetylcholine at muscarinic receptors. Our recent functional magnetic resonance imaging (fMRI) study has shown that sustained parahippocampal delay period activity during delayed match-to-sample performance in healthy young individuals predicted subsequent memory of visual stimuli on a recognition memory assessment 20 min later (Schon et al., 2004). The current study combined this fMRI paradigm with a pharmacological manipulation to test whether this long-term encoding-related delay activity is reduced in subjects who receive the muscarinic cholinergic antagonist scopolamine before fMRI scanning. Subsequent memory was predicted by sustained activity during brief memory delays bilaterally in the perirhinal/entorhinal cortex, in the right posterior parahippocampal and mid-fusiform gyri, and in the hippocampal body in healthy young individuals without a scopolamine challenge. This activity was reduced in subjects receiving scopolamine. The results are consistent with computational modeling data and behavioral pharmacological studies, suggesting that long-term encoding-related activity may be reduced if cholinergic receptors are blocked by scopolamine. C1 Boston Univ, Ctr Memory & Brain, Boston, MA 02215 USA. Boston Univ, Dept Psychol, Boston, MA 02215 USA. Boston Univ, Program Neurosci, Boston, MA 02215 USA. Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Stern, CE (reprint author), Boston Univ, Ctr Memory & Brain, 2 Cummington St, Boston, MA 02215 USA. EM chantal@bu.edu OI Atri, Alireza/0000-0003-4405-6973; Hasselmo, Michael/0000-0002-9925-6377 FU NIDA NIH HHS [DA16454]; NIMH NIH HHS [MH60013, R01 MH61492]; NINDS NIH HHS [R01 NS41636] NR 63 TC 95 Z9 95 U1 1 U2 8 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 9112 EP 9123 DI 10.1523/JNEUROSCI.1982-05.2005 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 971BD UT WOS:000232355200006 PM 16207870 ER PT J AU Goldstein, JM Jerram, M Poldrack, R Ahern, T Kennedy, DN Seidman, LJ Makris, N AF Goldstein, JM Jerram, M Poldrack, R Ahern, T Kennedy, DN Seidman, LJ Makris, N TI Hormonal cycle modulates arousal circuitry in women using functional magnetic resonance imaging SO JOURNAL OF NEUROSCIENCE LA English DT Article DE fMRI; emotion; arousal; hypothalamus; amygdala; women; HPA ID ESTROGEN-RECEPTOR-ALPHA; ADULT HUMAN BRAIN; PARAVENTRICULAR NUCLEUS; POSTMENOPAUSAL WOMEN; GENDER-DIFFERENCES; SEX-DIFFERENCES; RESPONSES; STIMULI; STRESS; MOOD AB Sex-specific behaviors are in part based on hormonal regulation of brain physiology. This functional magnetic resonance imaging (fMRI) study demonstrated significant differences in activation of hypothalamic-pituitary-adrenal (HPA) circuitry in adult women with attenuation during ovulation and increased activation during early follicular phase. Twelve normal premenopausal women were scanned twice during the early follicular menstrual cycle phase compared with late follicular/midcycle, using negative valence/high arousal versus neutral visual stimuli, validated by concomitant electrodermal activity (EDA). Significantly greater magnitude of blood oxygenation level-dependent signal changes were found during early follicular compared with midcycle timing in central amygdala, paraventricular and ventromedial hypothalamic nuclei, hippocampus, orbitofrontal cortex (OFC), anterior cingulate gyrus (aCING), and peripeduncular nucleus of the brainstem, a network of regions implicated in the stress response. Arousal (EDA) correlated positively with brain activity in amygdala, OFC, and aCING during midcycle but not in early follicular, suggesting less cortical control of amygdala during early follicular, when arousal was increased. This is the first evidence suggesting that estrogen may likely attenuate arousal in women via cortical-subcortical control within HPA circuitry. Findings have important implications for normal sex-specific physiological functioning and may contribute to understanding higher rates of mood and anxiety disorders in women and differential sensitivity to trauma than men. C1 Harvard Univ, Sch Med,Connors Ctr Womens Hlth & Gender Biol, Dept Psychiat,Div Womens Hlth, Dept Psychiat & Med,Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Mental Hlth Ctr, Publ Psychiat Div, Beth Israel Deaconess Hosp, Dept Psychiat, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02215 USA. Massachusetts Gen Hosp, Athinoula Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. MIT, Charlestown, MA 02129 USA. Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA. Harvard Univ, Ctr Morphometr Anal,Sch Med, Dept Neurol, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. Harvard Univ, Ctr Morphometr Anal,Sch Med, Dept Radiol, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. RP Goldstein, JM (reprint author), Connors Ctr Womens Hlth & Gender Biol, 1620 Tremont St,3rd Floor, Boston, MA 02120 USA. EM jill_goldstein@hms.harvard.edu RI Kennedy, David/H-3627-2012 FU NIMH NIH HHS [R01 MH56956] NR 43 TC 182 Z9 188 U1 6 U2 25 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 9309 EP 9316 DI 10.1523/JNEUROSCI.2239-05.2005 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 971BD UT WOS:000232355200027 PM 16207891 ER PT J AU Chroni, A Nieland, TJF Kypreos, KE Krieger, M Zannis, VI AF Chroni, A Nieland, TJF Kypreos, KE Krieger, M Zannis, VI TI SR-BI mediates cholesterol efflux via its interactions with lipid-bound ApoE. Structural mutations in SR-BI diminish cholesterol efflux SO BIOCHEMISTRY LA English DT Article ID HIGH-DENSITY-LIPOPROTEIN; RECEPTOR CLASS-B; APOLIPOPROTEIN-A-I; E-DEFICIENT MICE; BONE-MARROW-TRANSPLANTATION; SCAVENGER RECEPTOR; HDL RECEPTOR; TRANSGENIC MICE; GENE-TRANSFER; CELL-SURFACE AB Apolipoprotein E (apoE) and the lipoprotein receptor SR-BI play critical roles in lipid and lipoprotein metabolism. We have examined the cholesterol efflux from wild-type (WT) and mutant forms of SR-BI expressed in ldlA-7 cells using reconstituted discoidal particles consisting of apoE, 1-palmitoyl-2-oleoyl-L-phospatidylcholine (POPC), and cholesterol (C) as acceptors. POPC/C-apoE particles generated using apoE2, apoE3, apoE4, or carboxy-terminally truncated forms apoE4-165, apoE4-202, apoE4-229, and apoE4-259 caused similar (20-25%) cholesterol efflux from WT SR-131. Cholesterol efflux mediated by POPC/C-apoE was not enhanced in the presence of lipid-free apoE. The rate of cholesterol efflux mediated by particles containing the WT or carboxy-terminally truncated forms of apoE was decreased to approximately 30% of the WT control with the Q402R/Q418R mutant SR-131 form that is unable to bind native HDL normally but binds LDL. The rate of cholesterol efflux was further decreased to approximately 7% of the WT control with another SR-131 mutant (M158R) that binds neither HDL nor LDL. The level of binding of POPC/C-apoE particles (150 mu g/mL) to SR-BI mutant forms Q402R/Q418R and M158R was 70 and 8% of the WT control, respectively. SR-BI-dependent binding of lipid-free apoE to cells was undetectable, and cholesterol efflux was less than 0.5%. The findings establish that only lipid-bound apoE promotes SR-BI-mediated cholesterol efflux and that the amino-terminal region of residues 1 - 165 of apoE is sufficient for both receptor binding and cholesterol efflux. The SR-131- apoE interactions may contribute to overall cholesterol homeostasis in cells and tissues that express SR-131 and apoE. C1 Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Ctr Adv Biomed Res, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Biochem, Boston, MA 02118 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. CBR, Biomed Res Inst, Boston, MA 02115 USA. RP Zannis, VI (reprint author), Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Ctr Adv Biomed Res, 715 Albany St, Boston, MA 02118 USA. EM vzannis@bu.edu OI Kypreos, Kyriakos/0000-0001-6784-2710 FU NHLBI NIH HHS [HL68216, HL52212] NR 69 TC 31 Z9 31 U1 1 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD OCT 4 PY 2005 VL 44 IS 39 BP 13132 EP 13143 DI 10.1021/bi051029o PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 969RZ UT WOS:000232253700022 PM 16185081 ER PT J AU Otto, H Reche, PA Bazan, F Dittmar, K Haag, F Koch-Nolte, F AF Otto, H Reche, PA Bazan, F Dittmar, K Haag, F Koch-Nolte, F TI In silico characterization of the family of PARP-like poly(ADP-ribosyl) transferases (pARTs) SO BMC GENOMICS LA English DT Article ID ECTO-ADP-RIBOSYLTRANSFERASES; NAD-BINDING-SITE; CRYSTAL-STRUCTURE; DIPHTHERIA-TOXIN; RIBOSYLATING TOXINS; PROTEIN; GENOME; POLYMERASE; EVOLUTION; SEQUENCE AB Background: ADP-ribosylation is an enzyme-catalyzed posttranslational protein modification in which mono( ADP- ribosyl) transferases (mARTs) and poly( ADP- ribosyl) transferases (pARTs) transfer the ADPribose moiety from NAD onto specific amino acid side chains and/or ADP- ribose units on target proteins. Results: Using a combination of database search tools we identified the genes encoding recognizable pART domains in the public genome databases. In humans, the pART family encompasses 17 members. For 16 of these genes, an orthologue exists also in the mouse, rat, and pufferfish. Based on the degree of amino acid sequence similarity in the catalytic domain, conserved intron positions, and fused protein domains, pARTs can be divided into five major subgroups. All six members of groups 1 and 2 contain the H-Y-E trias of amino acid residues found also in the active sites of Diphtheria toxin and Pseudomonas exotoxin A, while the eleven members of groups 3 - 5 carry variations of this motif. The pART catalytic domain is found associated in Lego-like fashion with a variety of domains, including nucleic acid-binding, protein-protein interaction, and ubiquitylation domains. Some of these domain associations appear to be very ancient since they are observed also in insects, fungi, amoebae, and plants. The recently completed genome of the pufferfish T. nigroviridis contains recognizable orthologues for all pARTs except for pART7. The nearly completed albeit still fragmentary chicken genome contains recognizable orthologues for twelve pARTs. Simpler eucaryotes generally contain fewer pARTs: two in the fly D. melanogaster, three each in the mosquito A. gambiae, the nematode C. elegans, and the ascomycete microfungus G. zeae, six in the amoeba E. histolytica, nine in the slime mold D. discoideum, and ten in the cress plant A. thaliana. GenBank contains two pART homologues from the large double stranded DNA viruses Chilo iridescent virus and Bacteriophage Aeh1 and only a single entry ( from V. cholerae) showing recognizable homology to the pART-like catalytic domains of Diphtheria toxin and Pseudomonas exotoxin A. Conclusion: The pART family, which encompasses 17 members in the human and 16 members in the mouse, can be divided into five subgroups on the basis of sequence similarity, phylogeny, conserved intron positions, and patterns of genetically fused protein domains. C1 Univ Hamburg, Hosp Eppendorf, Inst Immunol, D-20246 Hamburg, Germany. DNAX Res Inst Molec & Cellular Biol Inc, Palo Alto, CA 94304 USA. Harvard Univ, Dana Farber Canc Inst, Boston, MA 02115 USA. Genentech Inc, Dept Mol Biol, San Francisco, CA 94080 USA. Genentech Inc, Dept Prot Engn, San Francisco, CA 94080 USA. Brigham Young Univ, Dept Integrat Biol, Provo, UT 84602 USA. RP Koch-Nolte, F (reprint author), Univ Hamburg, Hosp Eppendorf, Inst Immunol, Martinistr 52, D-20246 Hamburg, Germany. EM helge.otto@t-online.de; reche@research.dfci.harvard.edu; bazan.fernando@gene.com; katharinad@gmail.com; haag@uke.uni-hamburg.de; nolte@uke.uni-hamburg.de RI Bazan, J. Fernando/B-4562-2010; Reche, Pedro/B-1881-2013 OI Reche, Pedro/0000-0003-3966-5838 NR 57 TC 133 Z9 137 U1 0 U2 11 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PD OCT 4 PY 2005 VL 6 AR 139 DI 10.1186/1471-2164-6-139 PG 23 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 979DV UT WOS:000232923500001 PM 16202152 ER PT J AU Perlot, T Alt, FW Bassing, CH Suh, H Pinaud, E AF Perlot, T Alt, FW Bassing, CH Suh, H Pinaud, E TI Elucidation of IgH intronic enhancer functions via germ-fine deletion SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE germ-line transcription; immunoglobulin heavy chain; somatic hypermutation; VDJ recombination; class switch recombination ID CLASS-SWITCH RECOMBINATION; HEAVY-CHAIN LOCUS; MATRIX-ATTACHMENT REGIONS; IMMUNOGLOBULIN-KAPPA-GENE; SOMATIC HYPERMUTATION; V(D)J RECOMBINATION; CORE REGION; B-CELLS; TRANSCRIPTION; PROMOTER AB Studies of chimeric mice demonstrated that the core Ig heavy chain (IgH) intronic enhancer (iE mu) functions in V(D)J and class switch recombination at the IgH locus. To more fully evaluate the role of this element in these and other processes, we generated mice homozygous for germ-line mutations in which the core sequences of iE mu (cE mu) were either deleted (cE mu(Delta/Delta),11,1 mice) or replaced with a pgk-Neo(R) cassette (cE mu(N/N) mice). The cEI mu(Delta/Delta) mice had reduced B cell numbers, in association with impaired D to J(H) and V-H to DJ(H) rearrangement, whereas cE mu(N/N) mice had a complete block in IgH V(D)JH recombination, confirming that additional cis elements cooperate with iE mu to enforce D to JH recombination. In addition developing cE mu(Delta/Delta) and cE mu(N/N) B lineage cells had correspondingly decreased levels of germ-line transcripts from the J(H) region of the IgH locus (mu 0 and I mu transcripts); although both had normal levels of germ-line VH transcripts, suggesting that cE mu may influence IgH locus V(D)J recombination by influencing accessibility Of JH proximal regions of the locus. Consistent with chimera studies, peripheral cE mu(Delta/Delta) B cells had normal surface Ig and relatively normal class switch recombination. However, cE mu(Delta/Delta) B cells also had relatively normal somatic hypermutation of their IgH variable region genes, showing unexpectedly that the cE mu is not required for this process. The availability of mice with the iE mu mutation in their germ line will facilitate future studies to elucidate the roles of iE mu in V-H(D)J(H) recombination in the context of IgH chromatin structure and germ-line transcription. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res Inc, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Childrens Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. Univ Vienna, A-1010 Vienna, Austria. RP Alt, FW (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res Inc, 200 Longwood Ave, Boston, MA 02115 USA. EM alt@enders.tch.harvard.edu RI PINAUD, Eric/O-8443-2016 OI PINAUD, Eric/0000-0001-7405-9273 FU NIAID NIH HHS [AI 20047, R01 AI020047, R01 AI020047-25] NR 44 TC 103 Z9 103 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 4 PY 2005 VL 102 IS 40 BP 14362 EP 14367 DI 10.1073/pnas.0507090102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 971OD UT WOS:000232392900044 PM 16186486 ER PT J AU Grimm, J Kirsch, DG Windsor, SD Kim, CFB Santiago, PM Ntziachristos, V Jacks, T Weissleder, R AF Grimm, J Kirsch, DG Windsor, SD Kim, CFB Santiago, PM Ntziachristos, V Jacks, T Weissleder, R TI Use of gene expression profiling to direct in vivo molecular imaging of lung cancer SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID K-RAS; CATHEPSIN-B; CYSTEINE PROTEASES; ADENOCARCINOMA; PROLIFERATION; PROGRESSION; ACTIVATION; CARCINOMA; MUTATION; IMPACT AB Using gene expression profiling, we identified cathepsin cysteine proteases as highly up-regulated genes in a mouse model of human lung adenocarcinoma. Overexpression of cathepsin proteases in these lung tumors was confirmed by immunohistochemistry and Western blotting. Therefore, an optical probe activated by cathepsin proteases was selected to detect murine lung tumors in vivo as small as 1 mm in diameter and spatially separated. We generated 3D maps of the fluorescence signal and fused them with anatomical computed tomography images to show a close correlation between fluorescence signal and tumor burden. By serially imaging the same mouse, optical imaging was used to follow tumor progression. This study demonstrates the capability for molecular imaging of a primary lung tumor by using endogenous proteases expressed by a tumor. It also highlights the feasibility of using gene expression profiling to identify molecular targets for imaging lung cancer. C1 Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. MIT, Canc Res Ctr, Cambridge, MA 02139 USA. MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA. RP Weissleder, R (reprint author), Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. EM weissleder@helix.mgh.harvard.edu RI Grimm, Jan/B-1937-2008 FU NCI NIH HHS [P01 CA069246, P01 CA69246, P50 CA086355, P50 CA86355, R33 CA091807, R33 CA91807]; PHS HHS [R2492782] NR 26 TC 101 Z9 104 U1 0 U2 7 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 14404 EP 14409 DI 10.1073/pnas.0503920102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 971OD UT WOS:000232392900051 PM 16183744 ER PT J AU Stack, EC Kubilus, JK Smith, K Cormier, K Del Signore, SJ Guelin, E Ryu, H Hersch, SM Ferrante, RJ AF Stack, EC Kubilus, JK Smith, K Cormier, K Del Signore, SJ Guelin, E Ryu, H Hersch, SM Ferrante, RJ TI Chronology of behavioral symptoms and neuropathological sequela in R6/2 Huntington's disease transgenic mice SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE Huntington's disease; temporal phenotype; R6/2 transgenic mice; huntingtin ID NEURONAL INTRANUCLEAR INCLUSIONS; WILD-TYPE HUNTINGTIN; MOUSE MODEL; STRIATAL NEURONS; CAG REPEAT; KNOCK-IN; PROGRESSIVE FORMATION; TRINUCLEOTIDE REPEAT; PROLONGS SURVIVAL; COENZYME Q(10) AB Genetic murine models play an important role in the study of human neurological disorders by providing accurate and experimentally accessible systems to study pathogenesis and to test potential therapeutic treatments. One of the most widely employed models of Huntington's disease (HD) is the R6/2 transgenic mouse. To characterize this model further, we have performed behavioral and neuropathological analyses that provide a foundation for the use of R6/2 mice in preclinical therapeutic trials. Behavioral analyses of the R6/2 mouse reveal age-related impairments in dystonic movements, motor performance, grip strength, and body weight that progressively worsen until death. Significant neuropathological sequela, identified as increasing marked reductions in brain weight, are present from 30 days, whereas decreased brain volume is present from 60 days and decreased neostriatal volume and striatal neuron area, with a concomitant reduction in striatal neuron number, are present at 90 days of age. Huntingtin-positive aggregates are present at postnatal day 1 and increase in number and size with age. Our findings suggest that the R6/2 HD model exhibits a progressive HD-like behavioral and neuropathological phenotype that more closely corresponds to human HD than previously believed, providing further assurance that the R6/2 mouse is an appropriate model for testing potential therapies for HD. C1 Bedford VA Med Ctr, GRECC Unit 182B, Bedford, MA 01730 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Anat & Neurobiol, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Pathol & Psychiat, Boston, MA 02118 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA. RP Ferrante, RJ (reprint author), Bedford VA Med Ctr, GRECC Unit 182B, 200 Springs Rd, Bedford, MA 01730 USA. EM rjferr@bu.edu FU NCCIH NIH HHS [AT00613]; NINDS NIH HHS [NS045242, NS045806] NR 92 TC 147 Z9 148 U1 0 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD AUG 8 PY 2005 VL 490 IS 4 BP 354 EP 370 DI 10.1002/cne.20680 PG 17 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 959BA UT WOS:000231490700002 PM 16127709 ER PT J AU Demidova, TN Gad, F Zahra, T Francis, KP Hamblin, MR AF Demidova, TN Gad, F Zahra, T Francis, KP Hamblin, MR TI Monitoring photodynamic therapy of localized infections by bioluminescence imaging of genetically engineered bacteria SO JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY LA English DT Article DE bioluminescence imaging; luciferase; photodynamic therapy; poly-L-lysine photosensitizer conjugate; wounds; soft-tissue infections ID GRAM-NEGATIVE BACTERIA; ESCHERICHIA-COLI; STAPHYLOCOCCUS-AUREUS; IN-VIVO; WOUND INFECTIONS; INACTIVATION; MICE; ORGANIZATION; PORPHYRINS; EXPRESSION AB The increasing occurrence of multi-antibiotic resistant microbes has led to the search for alternative methods of killing pathogens and treating infections. Photodynamic therapy (PDT) uses the combination of non-toxic dyes and harmless visible light to produce reactive oxygen species that can kill mammalian and microbial cells. Although the photodynamic inactivation of bacteria has been known for over a hundred years, its use to treat infections has not been much developed. This may be partly due to the difficulty of monitoring the effectiveness of PDT in animal models of infection. In order to facilitate this monitoring process, we have developed a procedure that uses bioluminescent genetically engineered bacteria and a light sensitive imaging system to allow real-time visualization of infections. When these bacteria are treated with PDT in vitro, the loss of luminescence parallels the loss of colony-forming ability. We have developed several models of infections in wounds and soft-tissue abscesses in mice that can be followed by bioluminescence imaging. The size and intensity of the infection can be sequentially monitored in a non-invasive fashion in individual mice in real-time. When photosensitizers are introduced into the infected tissue followed by illumination with red light, a light-dose dependent loss of luminescence is seen. If the bacterium is invasive, the loss of luminescence correlates with increased survival of the mice, whilst animals in control groups die of sepsis within five days. Healing of the PDT treated wounds is not impaired and may actually be improved. This approach can allow many animal models of localized infections to be accurately monitored for efficacy of treatment by PDT. (c) 2005 Elsevier B.V. All rights reserved. C1 Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. Tufts Univ, Cell Mol & Dev Biol Program, Boston, MA 02111 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. Xenogen Corp, Alameda, CA USA. MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, BAR414,40 Blossom St, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu OI Hamblin, Michael/0000-0001-6431-4605 FU NIAID NIH HHS [AI 050875, R01 AI050875, R01 AI050875-01A2, R01 AI050875-02] NR 36 TC 65 Z9 68 U1 1 U2 17 PU ELSEVIER SCIENCE SA PI LAUSANNE PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND SN 1011-1344 J9 J PHOTOCH PHOTOBIO B JI J. Photochem. Photobiol. B-Biol. PD OCT 3 PY 2005 VL 81 IS 1 BP 15 EP 25 DI 10.1016/j.jphotobiol.2005.05.007 PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 971LC UT WOS:000232384500003 PM 16040251 ER PT J AU Szot, P White, SS Greenup, JL Leverenz, JB Peskind, ER Raskind, MA AF Szot, P White, SS Greenup, JL Leverenz, JB Peskind, ER Raskind, MA TI alpha(1)-Adrenoreceptor in human hippocarnpus: Binding and receptor subtype mRNA expression SO MOLECULAR BRAIN RESEARCH LA English DT Article DE norepinephrine; hippocampus; prazosin; alpha(1A)-adrenoreceptor; alpha(1D)-adrenoreceptor; in situ; receptor binding ID RAT-BRAIN; PHARMACOLOGICAL CHARACTERIZATION; ALPHA-1-ADRENERGIC RECEPTORS; ADRENERGIC-RECEPTOR; MOLECULAR-CLONING; CDNA; HIPPOCAMPUS; NOREPINEPHRINE; LOCALIZATION; SEQUENCE AB alpha(1)-Adrenoreceptors (AR), of which three subtypes exist (alpha(1A)-, alpha(1B)- and alpha(1D)-AR) are G-protein-coupled receptors that mediate the actions of norepinephrine and epinephrine both peripherally and centrally. In the CNS, alpha(1)-ARs are found in the hippocampus where animal studies have shown the ability of alpha(1)-AR agents to modulate long-term potentiation and memory; however, the precise distribution of alpha(1)-AR expression and its subtypes in the human brain is unknown making functional comparisons difficult. In the human hippocampus, 3 H-prazosin (a(1)-AR antagonist) labels only the dentate gyrus (molecular, granule and polymorphic layers) and the stratum lucidum of the CA3 homogenously. Human alpha(1A)-AR mRNA in the hippocampus is observed only in the dentate gyrus granule cell layer, while alpha(1D)-AR mRNA expression is observed only in the pyramidal cell layers of CA1, CA2 and CA3, regions where 3 H-prazosin did not bind. alpha(1B)-AR mRNA is not expressed at detectable levels in the human hippocampus. These results confirm a difference in hippocampal alpha(1)-AR localization between rat and humans and further describe a difference in the localization of the alpha(1A)- and alpha(1D)-AR mRNA subtype between rats and humans. Published by Elsevier B.V. C1 VA Puget Sound Hlth Care Syst, NW Network Mental Illness Res Educ & Clin Ctr S11, MIRECC S 116, Seattle, WA 98108 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Szot, P (reprint author), VA Puget Sound Hlth Care Syst, NW Network Mental Illness Res Educ & Clin Ctr S11, MIRECC S 116, 1660 S Columbian Way, Seattle, WA 98108 USA. EM szot@u.washington.edu NR 27 TC 12 Z9 13 U1 0 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 367 EP 371 DI 10.1016/j.molbrainres.2005.06.013 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 973IF UT WOS:000232515400021 ER PT J AU Boudoux, C Yun, SH Oh, WY White, WM Iftimia, NV Shishkov, M Bouma, BE Tearney, GJ AF Boudoux, C Yun, SH Oh, WY White, WM Iftimia, NV Shishkov, M Bouma, BE Tearney, GJ TI Rapid wavelength-swept spectrally encoded confocal microscopy SO OPTICS EXPRESS LA English DT Article ID IN-VIVO; REFLECTANCE MICROSCOPE; OPTICAL MICROSCOPE; HUMAN SKIN; LASER; MICROENDOSCOPE; DESIGN; FIBER; LENS AB Spectrally encoded confocal microscopy (SECM) is a technique that allows confocal microscopy to be performed through the confines of a narrow diameter optical fiber probe. We present a novel scheme for performing SECM in which a rapid wavelength swept source is used. The system allows large field of view images to be acquired at rates up to 30 frames/second. Images of resolution targets and tissue specimens acquired ex vivo demonstrate high lateral (1.4 mu m) and axial (6 mu m) resolution. Imaging of human skin was performed in vivo at depths of up to 350 mu m, allowing cellular and sub-cellular details to be visualized in real time. (c) 2005 Optical Society of America. C1 MIT, Harvard MIT Div Hlth Sci & Technol, Boston, MA 02114 USA. MIT, Dept Sci & Engn, Boston, MA 02114 USA. Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA 02114 USA. RP MIT, Harvard MIT Div Hlth Sci & Technol, Boston, MA 02114 USA. EM cboudoux@mit.edu RI Oh, Wang-Yuhl/C-2055-2011; Boudoux, Caroline/A-6399-2012 NR 22 TC 64 Z9 64 U1 0 U2 11 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1094-4087 J9 OPT EXPRESS JI Opt. Express PD OCT 3 PY 2005 VL 13 IS 20 BP 8214 EP 8221 DI 10.1364/OPEX.13.008214 PG 8 WC Optics SC Optics GA 973TF UT WOS:000232544800053 PM 19498851 ER PT J AU Kabrhel, C McAfee, AT Goldhaber, SZ AF Kabrhel, C McAfee, AT Goldhaber, SZ TI The contribution of the subjective component of the Canadian Pulmonary Embolism Score to the overall score in emergency department patients SO ACADEMIC EMERGENCY MEDICINE LA English DT Article DE pulmonary embolism; thromboembolism; venous thrombosis; Canadian Pulmonary Embolism Score; prediction ID SIMPLE CLINICAL-MODEL; D-DIMER; PROBABILITY; SCAN; MANAGEMENT; DIAGNOSIS; VALIDITY AB Background: Clinicians frequently use their experience to determine the pretest probability of pulmonary embolism (PE), although scoring systems are promoted as being more reliable. The Canadian Pulmonary Embolism Score (CPES) combines six objective questions and one subjective question. The CPES has been validated and appears to be useful for risk-stratifying patients. However, research suggests that subjective gestalt performs similarly to the CPES, and the influence of the subjective question on the predictive value of the CPES is not clear. Objectives: To determine the test characteristics of the CPES, its subjective question, and the degree to which the predictive value of the CPES is influenced by its individual questions. Methods: The authors performed a prospective observational study on a cohort of emergency department patients suspected of having PE. The authors compared patients' CPES results with the diagnosis of PE, calculated the test characteristics of the CPES, and determined the contribution of individual CPES questions to the score's overall predictive value. Results: Of 607 patients, 61 (10%) had PE. Of low-risk patients (CPES <= 4), 5.54% (n = 449; 95% confidence interval [95% CI] =.3.64% to 8.11%) had PE. The sensitivity (59.0%; 95% CI = 47.4% to 69.8%) and the negative predictive value (94.4%; 95% Cl = 92.8% to 95.9%) of the CPES were similar to the sensitivity (53.2%; 95% CI = 40.2% to 65.8%) and negative predictive value (93.5%; 95% Cl = 90.7% to 95.5%) of the subjective question alone. In multivariable analysis, nearly all of the predictive value of the CPES was derived from the subjective question. Conclusions: The predictive value of the CPES appears to be derived primarily from its subjective component. C1 Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Emergency Med, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc,Dept Med, Boston, MA 02115 USA. i3Magnify, Auburndale, MA USA. RP Kabrhel, C (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, 55 Fruit St,115 Clin Bldg, Boston, MA 02114 USA. EM ckabrhel@partners.org NR 15 TC 26 Z9 26 U1 0 U2 1 PU HANLEY & BELFUS INC PI PHILADELPHIA PA 210 S 13TH ST, PHILADELPHIA, PA 19107 USA SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD OCT PY 2005 VL 12 IS 10 BP 915 EP 920 DI 10.1197/j.aem.2005.05.030 PG 6 WC Emergency Medicine SC Emergency Medicine GA 971OO UT WOS:000232394000001 PM 16204134 ER PT J AU Yushkevich, P Dubb, A Xie, ZY Gur, R Gur, R Gee, J AF Yushkevich, P Dubb, A Xie, ZY Gur, R Gur, R Gee, J TI Regional structural characterization of the brain of schizophrenia patients SO ACADEMIC RADIOLOGY LA English DT Article DE brain atlases; registration; schizophrenia; brain morphology ID CHILDHOOD-ONSET SCHIZOPHRENIA; GRAY-MATTER; VOLUMETRIC-ANALYSIS; NEUROLEPTIC-NAIVE; WHITE-MATTER; SEGMENTATION; ADOLESCENCE; COMPETITION; HYPOTHESIS; CHILDREN AB Rationale and Objectives. We study morphologic characteristics and age-related changes in patients with schizophrenia to investigate whether abnormal neurodevelopment and brain structure have a role in the pathophysiological course of this disease. Materials and Methods. Our data consist of a set of cranial magnetic resonance images of 46 patients with schizophrenia and age- and sex-matched healthy controls. We deformed a template brain image to our set of subject images. Jacobian fields of these deformations were reduced to sets of 52 normalized region volumes for each subject by using a neuroanatornic atlas. Normalized regional volumes of the control and patient groups were compared by using Student t-test, and age correlation of each region volume was calculated for the two groups. All results were corrected for multiple comparisons by using permutation testing. We used a classifier based on support vector machines and a feature selection method to determine our ability to discriminate brains of controls from those of patients. Results. Analysis of normalized region volumes shows enlargement of the third ventricle in patients. The age-correlation study showed a significant positive correlation in the third ventricle and right thalamus of controls, but not patients. Using an average of 6.5 features, our classifier was able to correctly identify 72% of patients and 70% of controls. Conclusion. In addition to enlargement of the third ventricle, brains of patients with schizophrenia show a different pattern of age-related changes. C1 Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA. Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. VirtualScop LLC, Rochester, NY USA. RP Yushkevich, P (reprint author), Univ Penn, Dept Radiol, 3600 Market St,Suite 370, Philadelphia, PA 19104 USA. EM pauly2@grasp.upenn.edu OI Yushkevich, Paul/0000-0001-8543-4016 FU NCRR NIH HHS [M01RR0040]; NIA NIH HHS [AG-15116, AG-17586]; NIDA NIH HHS [DA-14418]; NIMH NIH HHS [MH60722, MH-19112, MH-62100]; NLM NIH HHS [LM-03504]; PHS HHS [P30-NNC] NR 58 TC 14 Z9 14 U1 0 U2 1 PU ASSOC UNIV RADIOLOGISTS PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523-2251 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD OCT PY 2005 VL 12 IS 10 BP 1250 EP 1261 DI 10.1016/j.acra.2005.06.014 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 967VR UT WOS:000232119800004 PM 16179202 ER PT J AU Intes, X Djeziri, S Ichalalene, Z Mincu, N Wang, Y St-Jean, P Lesage, F Hall, D Boas, D Polyzos, M Fleiszer, D Mesurolle, B AF Intes, X Djeziri, S Ichalalene, Z Mincu, N Wang, Y St-Jean, P Lesage, F Hall, D Boas, D Polyzos, M Fleiszer, D Mesurolle, B TI Time-domain optical mammography SoftScan: Initial results (vol 12, pg 934, 2005) SO ACADEMIC RADIOLOGY LA English DT Correction C1 ART Adv Res Technol Inc, St Laurent, PQ H4S 2A4, Canada. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA USA. McGill Univ, Montreal, PQ, Canada. RP Intes, X (reprint author), ART Adv Res Technol Inc, 2300 Alfred Nobel Blvd, St Laurent, PQ H4S 2A4, Canada. NR 1 TC 6 Z9 6 U1 0 U2 1 PU ASSOC UNIV RADIOLOGISTS PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523-2251 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD OCT PY 2005 VL 12 IS 10 BP 1355 EP 1355 DI 10.1016/j.acra.2005.08.029 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 967VR UT WOS:000232119800016 ER PT J AU Matthes, K Sahani, D Holalkere, NS Mino-Kenudson, M Brugge, WR AF Matthes, K Sahani, D Holalkere, NS Mino-Kenudson, M Brugge, WR TI Feasibility of endoscopic ultrasound-guided portal vein embolization with Enteryx SO ACTA GASTRO-ENTEROLOGICA BELGICA LA English DT Article DE EUS; Enteryx; portal vein embolisation ID VINYL ALCOHOL COPOLYMER; CEREBRAL ARTERIOVENOUS-MALFORMATIONS; LIQUID EMBOLIC AGENT; HEPATOCELLULAR-CARCINOMA; HEPATIC RESECTION; LIVER RESECTION; BLOOD-FLOW; HEPATECTOMY; PARTICLES; MIXTURE AB Background: Portal vein embolization (PVE) has been used as a preoperative strategy to induce hepatic lobar atrophy and contralateral lobe hypertrophy. We determined the feasibility of endoscopic ultrasound (EUS)-guided Enteryx (EVAL/ethylene-vinyl alcohol copolymer) embolization of the portal vein (EUS-PVE) in an animal model as a potential, minimally invasive, endoscopic technique. Methods : EUS-guided embolization of the portal vein (EUS-PVE) using Enteryx was performed in a Yorkshire breed swine. Portal pressure measurements were obtained before and after vascular embolization. The animal was carefully monitored for seven days for evidence of abdominal pain, shock, or bleeding. An upper abdominal contrast-CT scan was performed to verify the location of the embolus. Results : The PV pressure increased from 3 mmHg at baseline to a mean of 15 mmHg after EUS-PVE. The CT-scan on day 4 demonstrated Enteryx in the main portal vein with extension into the left branch. At sacrifice on day 7, a solid thrombus was visible grossly and histologically inside the main portal vein and the left branch of the portal vein. Conclusions : Selective embolization of the portal vein by EUS guidance appears to be feasible and a potential, minimally invasive, preoperative treatment option for patients undergoing extensive hepatectomy. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol,Gastrointestinal Pathol Serv, Boston, MA USA. RP Brugge, WR (reprint author), 55 Fruit St,Blake 4, Boston, MA 02114 USA. EM wbrugge@partners.org NR 21 TC 17 Z9 18 U1 2 U2 4 PU ACTA MEDICAL BELGICA PI BRUSSELS PA AVENUE CIRCULAIRE 138 A, B-1180 BRUSSELS, BELGIUM SN 0001-5644 J9 ACTA GASTRO-ENT BELG JI Acta Gastro-Enterol. Belg. PD OCT-DEC PY 2005 VL 68 IS 4 BP 412 EP 415 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 011XO UT WOS:000235302300002 PM 16432991 ER PT J AU Forchielli, ML Walker, WA AF Forchielli, ML Walker, WA TI The effect of protective nutrients on mucosal defense in the immature intestine SO ACTA PAEDIATRICA LA English DT Article; Proceedings Paper CT Symposium on Infant Nutrition CY DEC 11-12, 2003 CL Milan, ITALY DE protective nutrients; mucosal immunity; intestine; neonate ID NEONATAL NECROTIZING ENTEROCOLITIS; POLYUNSATURATED FATTY-ACIDS; PLACEBO-CONTROLLED TRIAL; HUMAN LACTOFERRIN; GASTROINTESTINAL-TRACT; DIETARY NUCLEOTIDES; ATOPIC DISEASE; HOST-DEFENSE; BRUSH-BORDER; PROBIOTICS AB Oral nutrition plays a dual role in the gut, providing nutrition to the body while affecting the function of the gastrointestinal tract. The exposure of the gut to food antigens, in the form of either beneficial or harmful nutritional substances, contributes to a vast array of physiological and pathologic gastrointestinal responses with secondary systemic implications. The immune system of the gastrointestinal tract is always involved in the first line of defense, and its actions are particularly important in the early period of life as maturation takes place. From maturation, a balance ensues in the regulatory mechanism of host defense, ultimately leading to either tolerance or immune reaction. This paper emphasizes how some nutrients may beneficially affect the gastrointestinal immune system's maturation in both term and especially premature neonates. C1 Univ Bologna, Dept Pediat, Bologna, Italy. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Walker, WA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Mucosal Immunol Labs, Boston, MA 02114 USA. EM allan_walker@hms.harvard.edu NR 45 TC 14 Z9 14 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0803-5253 J9 ACTA PAEDIATR JI Acta Paediatr. PD OCT PY 2005 VL 94 SU 449 BP 74 EP 83 DI 10.1080/08035320510043592 PG 10 WC Pediatrics SC Pediatrics GA 980KF UT WOS:000233016700014 PM 16214770 ER PT J AU Backus, LI Boothroyd, D Deyton, LR AF Backus, LI Boothroyd, D Deyton, LR TI HIV, hepatitis C and HIV/hepatitis C virus co-infection in vulnerable populations 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 alcoholism; drug users; hepatitis C virus infection; HIV infection; psychiatry; risk factors ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; ALPHA-2A PLUS RIBAVIRIN; INTERFERON-ALPHA; INFECTED PATIENTS; NATURAL-HISTORY; LIVER FIBROSIS; CLINICAL-COURSE; PROGRESSION; MORTALITY AB Objective: To describe basic patient demographic and clinical characteristics of HIV-infected and HIV/hepatitis C virus (HCV)-co-infected patients receiving care in the Department of Veterans Affairs (VA) with a focus on some patient factors that place such patients at an increased risk of poor health outcomes. Design: An observational retrospective cohort study. Methods: The study cohort consisted of veterans in the VA Immunology Case Registry who received care in the VA in 2002. Results: Of 18 349 HIV-infected patients, 6782 (37.0%) were HCV seropositive. Compared with HIV-alone-infected patients, HIV/HCV-co-infected patients were older, more likely to be men, more likely to be black or Hispanic, and more likely to report intravenous drug use as a risk factor for HIV acquisition. HIV/HCV-co-infected patients were more likely to have diagnoses of mental health illness, depression, alcohol abuse, substance abuse and hard drug abuse compared with HIV-alone-infected patients. Co-infected patients were less likely to have a history of an AIDS opportunistic infection ever and were less likely to have received HIV antiretroviral drugs in 2002. Conclusion: The VA's HIV and HIV/HCV-co-infected patient populations have very high rates of additional comorbid conditions that complicate both the pharmacological therapy and clinical course of both HIV and HCV infections. Given the overlap in viral illness and comorbidities, optimal models of integrated care need to be developed for populations with HIV, HCV, and HIV/HCV co-infection and who need substance abuse treatment or mental healthcare. (c) 2005 Lippincott Williams & Wilkins C1 US Dept Vet Affairs, PHSHCG 13B, Washington, DC 20420 USA. US Dept Vet Affairs, Ctr Qual Management Publ Hlth, Palo Alto, CA USA. RP Deyton, LR (reprint author), US Dept Vet Affairs, PHSHCG 13B, 810 Vermont Ave NW, Washington, DC 20420 USA. EM dr.bopper.deyton@hq.med.va.gov NR 39 TC 41 Z9 42 U1 0 U2 3 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 S13 EP S19 DI 10.1097/01.aids.0000192065.09281.01 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 988DF UT WOS:000233570900004 PM 16251809 ER PT J AU Huckans, MS Blackwell, AD Harms, TA Indest, DW Hauser, P AF Huckans, MS Blackwell, AD Harms, TA Indest, DW Hauser, P TI Integrated hepatitis C virus treatment: addressing comorbid substance use disorders and HIV infection 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 comorbidity; hepatitis C; HIV; literature review; mental disorders; prevalence; substance-related disorders ID SEVERE MENTAL-ILLNESS; HUMAN-IMMUNODEFICIENCY; VETERANS; PREVALENCE; SERVICES; HEALTH; DEPRESSION; HIV/AIDS; AIDS AB Objectives: To examine hepatitis C virus (HCV) and HIV testing patterns within the Northwest Veterans Integrated Service Network (VISN 20). Methods: Using a comprehensive VISN 20 database, we retrospectively reviewed medical records of 293 445 veterans. Results: 32.8% of patients were tested for HCV, 5.5% were tested for HIV, and 4.3% were co-tested. Of those tested, 12.3% were HCV positive, 5.4% were HIV positive, and 1.6% were co-infected. 79.1 % of HIV-positive patients were tested for HCV, 29.2% of whom tested positive. 34.8% of HCV-positive patients were tested for HIV, 4.9% of whom tested positive. Of those tested, HCV-positive patients were significantly more likely than HCV-negative patients to test positive for HIV; HIV-positive patients were no more likely to test positive for HCV than HIV-negative patients. HIV-positive patients with substance use disorders (SUD) were significantly more likely to test HCV positive than those without. Within the total sample, veterans with SUD were significantly more likely to be tested for both diseases and to test positive for HCV but not HIV. After controlling for other categories of SUD, veterans with a history of cocaine abuse compared with those without were at an increased risk of HIV infection and co-infection. Conclusion: 79.1 % of HIV-positive but only 34.8% of HCV-positive veterans were cotested, suggesting barriers to HIV testing may exist in VISN 20. Results also indicate that HCV-positive patients are at increased risk for HIV infection and that HIV-positive patients with SUD are at increased risk of HCV infection; routine co-testing for these patients is therefore warranted. Given significant co-infection rates, HCV and HIV screening and testing should be increasingly integrated. Increased infection rates among patients with SUD also warrant integration of HCV and HIV screening and testing into mental health and addiction programmes. (c) 2005 Lippincott Williams & Wilkins. C1 Portland VA Med Ctr, Behav Hlth & Clin Neurosci Div, Portland, OR 97239 USA. Portland VA Med Ctr, NW Hepatitis C Resource Ctr, Portland, OR 97239 USA. Portland VA Med Ctr, JENS Lab, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR USA. Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR USA. Univ Oregon, Dept Anthropol, Eugene, OR USA. RP Hauser, P (reprint author), Portland VA Med Ctr, Behav Hlth & Clin Neurosci Div, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM peter.hauser2@med.va.gov RI Blackwell, Aaron/B-5258-2008 OI Blackwell, Aaron/0000-0002-5871-9865 NR 26 TC 19 Z9 19 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 S106 EP S115 DI 10.1097/01.aids.0000192078.49185.b0 PG 10 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 988DF UT WOS:000233570900017 PM 16251805 ER PT J AU Safren, SA Kumarasamy, N James, R Raminani, S Solomon, S Mayer, KH AF Safren, SA Kumarasamy, N James, R Raminani, S Solomon, S Mayer, KH TI ART adherence, demographic variables and CD4 outcome among HIV-positive patients on antiretroviral therapy in Chennai, India SO AIDS CARE-PSYCHOLOGICAL AND SOCIO-MEDICAL ASPECTS OF AIDS/HIV LA English DT Article ID SELF-REPORTED ADHERENCE; DRUG-RESISTANCE; CLINICAL-TRIALS; INFECTION; MEDICATION; REGIMENS; DISEASE; ADULTS; CARE AB This is an analysis of available chart data recorded by HIV counselors and physicians on patient adherence and CD4 count in 304 patients with HIV who were prescribed antiretroviral therapy ( ART) in Chennai, India. HIV counselors had categorized the majority of patients' adherence as 'regular' (74.3%), with a significant minority being categorized as 'irregular' (17.8%), or 'recently missed some doses' (6.9%). Those categorized as 'irregular' had significantly lower CD4 counts than those classified as 'regular'. Adherence was not associated with any demographic variable; however, it was associated with current CD4 and with change in CD4 since initiation of ART. This association was significant over and above the effects of time on ART. The most common reason for non-adherence was cost (32%), followed by the inability to return for a refill (i.e., patients who were unable or refused to obtain medicines elsewhere) (7.5%). These data suggest that although most patients in this Indian cohort reported regular adherence to ART, a subset admitted to less than regular adherence to ART, and those who admitted to less than regular adherence had worse CD4 outcomes. These data do not support concerns about adherence as a reason to withhold ART in developing countries, nor do they support claims that patients in India who struggle with adherence would be unwilling or unable to admit to non-adherence to health care professionals. C1 Fenway Community Hlth Res Dept, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. YRG CARE, Madras, Tamil Nadu, India. Brown Univ, Providence, RI 02912 USA. RP Safren, SA (reprint author), Fenway Community Hlth Res Dept, 7 Haviland St, Boston, MA 02115 USA. NR 20 TC 37 Z9 38 U1 0 U2 1 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0954-0121 J9 AIDS CARE JI Aids Care-Psychol. Socio-Med. Asp. Aids-Hiv PD OCT PY 2005 VL 17 IS 7 BP 853 EP 862 DI 10.1080/09540120500038439 PG 10 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychology, Multidisciplinary; Respiratory System; Social Sciences, Biomedical SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychology; Respiratory System; Biomedical Social Sciences GA 958FC UT WOS:000231429100008 PM 16120502 ER PT J AU Berg, MB Safren, SA Mimiaga, MJ Grasso, C Boswell, S Mayer, KH AF Berg, MB Safren, SA Mimiaga, MJ Grasso, C Boswell, S Mayer, KH TI Nonadherence to medical appointments is associated with increased plasma HIV RNA and decreased CD4 cell counts in a community-based HIV primary care clinic SO AIDS CARE-PSYCHOLOGICAL AND SOCIO-MEDICAL ASPECTS OF AIDS/HIV LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; INFECTION; ADHERENCE; OUTCOMES AB This study examined the association of appointment nonadherence to markers of disease severity using one year of demographic and health information on 995 individuals with HIV in primary care at an urban community health centre. At the latest visit, 106 of 946 valid cases (11.2%) had a CD4 less than or equal to 200, and 454 of 936 valid cases (48.5%) had detectable plasma HIV RNA ( greater than 50 copies/ml). Using logistic regression, appointment nonadherence ( number of missed appointments) was a significant predictor (p < .03) of having an AIDS-defining CD4 count over and above the effects of number of kept appointments (p < .0001), and whether or not the patient was taking HAART (p < .002). Appointment nonadherence was also a significant predictor (p < .05) of having a detectable viral load over and above the effects of number of kept appointments (p < .003), HAART (p < .0001) and age (p < .004). Looking only at individuals with a detectable viral load at the earliest visit, the only significant unique predictor of improvement to an undetectable viral load at the latest visit was being on HAART (p < .05). Looking at those only with an undetectable viral load at the earliest visit, the only predictor of declining to a detectable viral load was number of kept appointments (p < 003), and being on HAART (p < .05). C1 Fenway Community Hlth, Res & Evaluat Dept, Boston, MA 02115 USA. Wheaton Coll, Norton, MA 02766 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Brown Univ, Miriam Hosp, Providence, RI USA. RP Safren, SA (reprint author), Fenway Community Hlth, Res & Evaluat Dept, 7 Haviland St, Boston, MA 02115 USA. EM ssafren@partners.org FU NIAID NIH HHS [5P30AI027763]; NIMH NIH HHS [MH 66660] NR 11 TC 80 Z9 83 U1 0 U2 1 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0954-0121 J9 AIDS CARE JI Aids Care-Psychol. Socio-Med. Asp. Aids-Hiv PD OCT PY 2005 VL 17 IS 7 BP 902 EP 907 DI 10.1080/09540120500101658 PG 6 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychology, Multidisciplinary; Respiratory System; Social Sciences, Biomedical SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychology; Respiratory System; Biomedical Social Sciences GA 958FC UT WOS:000231429100012 PM 16120506 ER PT J AU Peskind, ER Riekse, R Quinn, JF Kaye, J Clark, CM Farlow, MR DeCarli, C Chabal, C Vavrek, D Raskind, MA Galasko, D AF Peskind, ER Riekse, R Quinn, JF Kaye, J Clark, CM Farlow, MR DeCarli, C Chabal, C Vavrek, D Raskind, MA Galasko, D TI Safety and acceptability of the research lumbar puncture SO ALZHEIMER DISEASE & ASSOCIATED DISORDERS LA English DT Article DE Alzheimer disease; lumbar puncture; post lumbar-puncture headache ID TECHNOLOGY-ASSESSMENT SUBCOMMITTEE; SPINAL NEEDLES; ALZHEIMERS-DISEASE; AMERICAN-ACADEMY; CLINICAL-TRIAL; DOUBLE-BLIND; HEADACHE; THERAPEUTICS; PREVENTION; NEUROLOGY AB Three hundred forty-two Subjects underwent 428 research lumbar punctures for Studies of cerebrospinal fluid (CSF) biomarkers. Subjects were 67 Alzheimer disease or mild cognitive impairment (AD/MCI) patients and 275 cognitively normal adults aged 21 to 88. Lumbar puncture was performed in the lateral decubitus or sitting position using the Sprotte 24g atraumatic spinal needle. Up to 34 ill] of cerebrospinal fluid were collected. Anxiety and pain experienced during lumbar puncture were rated on a visual analog scale. The frequency of any adverse event (11.7%), clinically significant adverse events (3.97%), and typical Post-lumbar puncture headache (PLPHA) (0.93%) was low. Risk of post-lumbar puncture headache was un-related to age, gender, position during lumbar puncture, till of cerebrospinal fluid collected, or minutes of recumbent rest following lumbar puncture. The frequency of post-lumbar puncture headache was lower in AD/MCI (P = 0.03) than any other subject group. Anxiety and pain ratings were low, Younger subjects reported more anxiety than old (P = 0.001) and AD/MCI subjects (P = 0.008) and more pain than older normal subjects (P = 0.013). Pain ratings for women were higher than those for men (P = 0.006). Using the Sprotte 24g spinal needle, research lumbar puncture can be performed with a very low rate of clinically significant adverse events and with good acceptability in cognitively impaired persons and cognitively normal adults Of all ages. C1 Univ Washington, Educ & Clin Ctr, VA Puget Sound Hlth Care Syst, MIRECC,Sch Med, Seattle, WA 98108 USA. Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. Oregon Hlth Sci Univ, Dept Neurol, Portland, OR 97201 USA. Univ Penn, Inst Aging, Dept Neurol, Philadelphia, PA 19104 USA. Portland VA Med Ctr, Portland, OR USA. Indiana Univ, Dept Neurol, Sch Med, Indianapolis, IN USA. Univ Calif Davis, Dept Neurol, Sacramento, CA 95616 USA. Univ Washington, Sch Med, Dept Anesthesiol, Seattle, WA 98195 USA. Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA. VA Med Ctr, San Diego, CA USA. RP Peskind, ER (reprint author), Univ Washington, Educ & Clin Ctr, VA Puget Sound Hlth Care Syst, MIRECC,Sch Med, 1660 S Columbian Way, Seattle, WA 98108 USA. EM peskind@u.washington.edu RI DeCarli, Charles/B-5541-2009; OI Kaye, Jeffrey/0000-0002-9971-3478 FU NCRR NIH HHS [M01 RR00034]; NIA NIH HHS [AG010133, AG023185, AG05136, AG08419, AG10124] NR 21 TC 99 Z9 99 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0893-0341 J9 ALZ DIS ASSOC DIS JI Alzheimer Dis. Assoc. Dis. PD OCT-DEC PY 2005 VL 19 IS 4 BP 220 EP 225 DI 10.1097/01.wad.0000194014.43575.fd PG 6 WC Clinical Neurology; Pathology SC Neurosciences & Neurology; Pathology GA 993ZD UT WOS:000233998000008 PM 16327349 ER PT J AU Spertus, J Peterson, E Conard, MW Heidenreich, PA Krumholz, HM Jones, P McCullough, PA Pina, I Tooley, J Weintraub, WS Rumsfeld, JS AF Spertus, J Peterson, E Conard, MW Heidenreich, PA Krumholz, HM Jones, P McCullough, PA Pina, I Tooley, J Weintraub, WS Rumsfeld, JS CA Cardiovascular Outcomes Res Consor TI Monitoring clinical changes in patients with heart failure: A comparison of methods SO AMERICAN HEART JOURNAL LA English DT Article ID QUALITY-OF-LIFE; DISEASE MANAGEMENT; HEALTH-STATUS; NATRIURETIC PEPTIDE; QUESTIONNAIRE; READMISSION; RELIABILITY; EFFICACY; VALIDITY; OUTCOMES AB Background Although monitoring the clinical status of patients with heart failure rests at the core of clinical medicine, the ability of different techniques to reflect clinical change has not been evaluated. This study sought to describe changes in various measures of disease status associated with gradations of clinical change. Methods A prospective, 14-center cohort of 476 outpatients was assessed at baseline and 6 +/- 2 weeks to compare changes in 7 heart failure measures with clinically observed change. Measures included health status instruments (the Kansas City Cardiomyopathy Questionnaire [KCCQ], Short Form-12, and EQ-5D), physician-assessed functional class (New York Heart Association [NYHA]), an exercise test (6-minute walk), patient weight, and a biomarker (B-type natriuretic peptide). Cardiologists, blinded to all measures except weight and NYHA, categorized clinical change ranging from large deterioration to large improvement. Results The KCCQ, NYHA, and 6-minute walk test were most sensitive to clinical change. For patients with large, moderate, and small deteriorations, the KCCQ decreased by 25 +/- 16, 17 +/- 14, and 5.3 +/- 11 points, respectively. For patients with small, moderate, and large improvements, the KCCQ increased by 5.7 +/- 16, 10.5 +/- 16, and 22.3 +/- 16 points, respectively (P <.01 for all compared with the no change group). New York Heart Association and 6-minute walk distance were significantly different for those with moderate and large changes ( P <.05) but neither revealed a difference between those with small versus no clinical deterioration. The KCCQ had the highest c statistic for monitoring individual patients, followed by NYHA and 6-minute walk. Conclusion The KCCQ, followed by the NYHA and the 6-minute walk test, most accurately reflected clinical change in patients with heart failure. C1 St Lukes Hosp, Mid Amer Heart Inst, Kansas City, MO 64111 USA. Univ Missouri, Kansas City, MO 64110 USA. Pharmacia Inc, Chicago, IL USA. Yale Univ, New Haven, CT USA. Denver VA Med Ctr, Denver, CO USA. Palo Alto VA Med Ctr, Palo Alto, CA USA. Duke Univ, Med Ctr, Durham, NC USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Emory Univ, Atlanta, GA 30322 USA. RP Spertus, J (reprint author), 4401 Wornall Rd, Kansas City, MO 64111 USA. EM spertusj@umkc.edu OI Heidenreich, Paul/0000-0001-7730-8490 NR 26 TC 153 Z9 155 U1 0 U2 7 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD OCT PY 2005 VL 150 IS 4 BP 707 EP 715 DI 10.1016/j.ahj.2004.12.010 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 979NY UT WOS:000232953300016 PM 16209970 ER PT J AU Visnegarwala, F Raghavan, SS Mullin, CM Bartsch, G Wang, J Kotler, D Gibert, CL Shlay, J Grunfeld, C Carr, A El-Sadr, W AF Visnegarwala, F Raghavan, SS Mullin, CM Bartsch, G Wang, J Kotler, D Gibert, CL Shlay, J Grunfeld, C Carr, A El-Sadr, W CA Terry Beirn Community Program TI Sex differences in the associations of HIV disease characteristics and body composition in anti retroviral-naive persons SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE HIV infection; antiretroviral-naive patients; sex differences; body composition; anthropometric analysis; bioelectrical impedance ID HUMAN-IMMUNODEFICIENCY-VIRUS; ENERGY-EXPENDITURE; FAT DISTRIBUTION; INFECTED WOMEN; WEIGHT-LOSS; MASS INDEX; ANTIRETROVIRAL THERAPY; IMPEDANCE ANALYSIS; RACIAL-DIFFERENCES; ADIPOSE-TISSUE AB Background: Data on associations of body composition with HIV disease characteristics are limited. Objective: We compared sex-specific associations between HIV disease characteristics and body composition in an racially-ethnically diverse cohort of antiretroviral-naive patients. Design: The study was a cross-sectional analysis of participants enrolled in a metabolic substudy of a multicenter trial. Regional fat was measured, and total body fat (TBF) was derived by using the Durnin-Womersley formula (DWF) and bioelectrical impedance analysis (BIA). Body cell mass (BCM) was measured by BIA. Results: Among 422 participants, 22% were women, 60% were African American, and 36% had prior AIDS-defining illnesses. Mean (+/- SD) age was 38.2 +/- 9.6 y, CD4(+) count was 215 184 cellS/mm(3), and HIV RNA log(10) was 5.0 +/- 0.8 copies/mL. On multivariate analysis, women with AIDS-defining illness had significantly (P < 0.005) lower regional body fat and TBF (BIA: - 9.5 kg; DWF: -7.3 kg) but nonsignificantly lower BCM (- 1.3 kg) than did women without such illnesses, whereas men with AIDS-defining illness had significantly (P < 0.005) lower BCM (- 1.7 kg) but nonsignificantly lower TBF (BIA: - 1.3 kg; DWF: - 1.83 kg) than did men without such illnesses (P < 0.05 for sex differences in TBF). Significant negative associations of HIV RNA with BCM (-0.9 kg/log RNA; P = 0.03), TBF by BIA (- 1.4 kg/log RNA; P = 0.05) and by DWF (- 1.6 kg/log RNA; P = 0.01), and regional fat were observed in men only. Conclusions: The effect of prior AIDS illness on body fat differed significantly between the sexes: women with prior AIDS-defining illness had significantly less fat than did women without such illnesses. An independent effect of HIV viremia on BCM and fat was seen in men. These distinctions may be due to inherent biological differences between the sexes. C1 Baylor Coll Med, Infect Dis Sect, Dept Med, Houston, TX 77030 USA. HART, Houston, TX USA. Harlem Hosp Med Ctr, New York, NY USA. Columbia Univ, New York, NY 10027 USA. Univ Minnesota, Sch Publ Hlth, Minneapolis, MN 55455 USA. Columbia Univ, St Lukes Roosevelt Hosp, Body Composit Unit, New York, NY 10027 USA. George Washington Univ, Washington, DC 20052 USA. Vet Affairs Med Ctr, Washington, DC 20422 USA. Denver Community Program Clin Res AIDS, Denver, CO USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. San Francisco Vet Affairs Med Ctr, San Francisco, CA USA. St Vincents Hosp, Sydney, NSW 2010, Australia. RP Visnegarwala, F (reprint author), Baylor Coll Med, Infect Dis Sect, Dept Med, 1 Baylor Plaza,BCM 465 EC, Houston, TX 77030 USA. EM fehmidav@bcm.tmc.edu FU PHS HHS [5U0142170-1, 5U0146362-03] NR 48 TC 19 Z9 20 U1 0 U2 0 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 850 EP 856 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 973CN UT WOS:000232500600020 PM 16210716 ER PT J AU Miljanovic, B Trivedi, KA Dana, MR Gilbard, JP Buring, JE Schaumberg, DA AF Miljanovic, B Trivedi, KA Dana, MR Gilbard, JP Buring, JE Schaumberg, DA TI Relation between dietary n-3 and n-6 fatty acids and clinically diagnosed dry eye syndrome in women SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE epidemiology; dry eye syndrome; diet; n-3 fatty acids; n-6 fatty acids; risk factors; women ID GAMMA-LINOLENIC ACID; PRIMARY SJOGRENS-SYNDROME; NUTRIENT INTAKE; OMEGA-3-FATTY-ACIDS; THERAPY; DISEASE; CLASSIFICATION; PREVALENCE; SICCA; RISK AB Background: Dry eye syndrome (DES) is a prevalent condition, but information on risk or protective factors is lacking. Objective: We aimed to determine the association between the dietary intake and ratio of n-3 and n-6 fatty acids (FAs) and DES occurrence. Design: Of the 39 876 female health professionals in the Women's Health Study (WHS), 32 470 women aged 45-84 y who provided information on diet and DES were cross-sectionally studied. We assessed FA intakes by using a validated food-frequency questionnaire and assessed DES by using self-reports of clinically diagnosed cases. Of the sample, 1546 (4.7%) subjects reported DES. We used logistic regression models to estimate the odds ratios (ORs) and 95% CIs to describe the relation of FA intake with DES. Results: After adjustment for demographic factors, hormone therapy, and total fat intake, the OR for the highest versus the lowest quintile of n-3 FAs was 0.83 (95% CI: 0.70, 0.98; P for trend = 0.05). A higher ratio of n-6 to n-3 FA consumption was associated with a significantly increased risk of DES (OR: 2.5 1; 95 % CI: 1.13, 5.58) for > 15:1 versus <4:1 (P for trend = 0.01). In addition, tuna consumption [1 serving was 113 g (4 oz)] was inversely associated with DES (OR: 0.81; 95% CI: 0.66, 0.99 for 2-4 servings/wk; OR: 0.32; 95% CI: 0.13, 0.79 for 5- 6 servings/wk versus <= 1 serving/wk; P for trend = 0.005). Conclusions: These results suggest that a higher dietary intake of n -3 FAs is associated with a decreased incidence of DES in women. These findings are consistent with anecdotal clinical observations and postulated biological mechanisms. C1 Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. Schepens Eye Res Inst, Boston, MA USA. Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Schaumberg, DA (reprint author), Div Prevent Med, 900 Commonwealth Ave E, Boston, MA 02215 USA. EM dschaumberg@rics.bwh.harvard.edu FU NCI NIH HHS [R01 CA047988, CA47988]; NHLBI NIH HHS [HL43851, R01 HL043851] NR 42 TC 102 Z9 107 U1 2 U2 17 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 887 EP 893 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 973CN UT WOS:000232500600025 PM 16210721 ER PT J AU Robert, ME Washington, MK Lee, JR Goldenring, JR Bronner, MP Goldblum, JR Greenson, JK Haber, MM Hart, JA Lamps, LW Lauwers, GY Lewin, D Lazenby, AJ Montgomery, E Crawford, JM AF Robert, ME Washington, MK Lee, JR Goldenring, JR Bronner, MP Goldblum, JR Greenson, JK Haber, MM Hart, JA Lamps, LW Lauwers, GY Lewin, D Lazenby, AJ Montgomery, E Crawford, JM TI Rab11a immunohistochemical analysis does not distinguish indefinite, low-, and high-grade dysplasia in Barrett esophagus SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE Barrett esophagus; Rab11a; p53; immunohistochemistry; dysplasia; interobserver variation ID P53 PROTEIN ACCUMULATION; FLOW-CYTOMETRY; PREDICTIVE MARKER; ADENOCARCINOMA; PROGRESSION; CARCINOMA; DIAGNOSIS; RISK; IMMUNOREACTIVITY; EXPRESSION AB Our aim was to determine whether p53 and Rab11a immunoreactivity enhance diagnostic assessment Of esophageal dysplasia. Histologic sections from 68 cases of Barrett esophagus obtained as part of a 12-institution study were stained with antibodies to p53 and Rab11a, randomized, and coded. The mucosal surface layer and deeper glands were scored blindly on a semiquantitative scale. The correlations between p53 and Rab11a scoring with the consensus diagnosis of dysplasia were analyzed. The histologic scale was as follows: no dysplasia, indefinite, low-grade dysplasia, high-grade dysplasia, intramucosal carcinoma, and invasive carcinoma. Rab11a staining was most prominent in epithelia negative for dysplasia but with regenerative features. There was an inverse relationship between Rab11a staining and findings of surface dysplasia (P <.02, chi(2)). However, statistical significance largely reflected loss of Rab11 a immunoreactivity in intramucosal and invasive carcinoma, which was not a diagnostic dilemma. There was a strong positive correlation of p53 immunoreactivity with an increasing degree of epithelial dysplasia and carcinoma (P < .03, chi(2)). Rab11a immunoreactivity did not enhance the diagnostic assessment of dysplasia in Barrett esophagus. The previously reported positive correlation of p53 immunoreactivity with the presence of dysplasia in Barrett esophagus was confirmed. C1 Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06520 USA. Vanderbilt Univ, Nashville, TN USA. Med Coll Georgia, Inst Mol Med & Genet, Augusta, GA 30912 USA. Med Coll Georgia, Dept Pathol, Augusta, GA 30912 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Med Coll Penn & Hahnemann Univ, Philadelphia, PA 19102 USA. Univ Chicago, Chicago, IL 60637 USA. Univ Arkansas, Little Rock, AR 72204 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Med Univ S Carolina, Charleston, SC 29425 USA. Univ Alabama, Birmingham, AL USA. Johns Hopkins Med Ctr, Baltimore, MD USA. Univ Florida, Gainesville, FL USA. Vanderbilt Univ, Dept Surg, Nashville, TN 37240 USA. RP Robert, ME (reprint author), Yale Univ, Sch Med, Dept Pathol, 310 Cedar St,POB 208023, New Haven, CT 06520 USA. NR 29 TC 1 Z9 2 U1 0 U2 0 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD OCT PY 2005 VL 124 IS 4 BP 519 EP 527 DI 10.1309/7X4GAXT15H50B48P PG 9 WC Pathology SC Pathology GA 966RD UT WOS:000232037700006 PM 16146818 ER PT J AU Fong, D Shen, P AF Fong, D Shen, P TI Temporal pattern of mean corpuscular volume as putative evidence for thalassemia SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Clinical-Pathology CY OCT 08-11, 2005 CL Seattle, WA SP Amer Soc Clin Pathol C1 Univ Colorado, Sch Med, Dept Pathol, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Dept Pathol & Lab Med, Denver, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD OCT PY 2005 VL 124 IS 4 MA 048 BP 641 EP 642 PG 2 WC Pathology SC Pathology GA 966RD UT WOS:000232037700070 ER PT J AU Fong, D Shen, P AF Fong, D Shen, P TI Erythrocytosis is frequent in adult iron deficiency anemia SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Society-for-Clinical-Pathology CY OCT 08-11, 2005 CL Seattle, WA SP Amer Soc Clin Pathol C1 Univ Colorado, Sch Med, Denver, CO 80202 USA. Denver Vet Affairs Med Ctr, Denver, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD OCT PY 2005 VL 124 IS 4 MA 060 BP 646 EP 646 PG 1 WC Pathology SC Pathology GA 966RD UT WOS:000232037700082 ER PT J AU El-Serag, HB Kvapil, P Hacken-Bitar, J Kramer, JR AF El-Serag, HB Kvapil, P Hacken-Bitar, J Kramer, JR TI Abdominal obesity and the risk of Barrett's esophagus SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID GASTROESOPHAGEAL-REFLUX SYMPTOMS; BODY-FAT DISTRIBUTION; WAIST-HIP RATIO; COMPUTED-TOMOGRAPHY; GASTRIC CARDIA; UNITED-STATES; MASS INDEX; ADENOCARCINOMA; DISEASE; WOMEN AB BACKGROUND: The association between overweight/obesity and the risk of Barrett's esophagus (BE) is unclear. Further, the association between body fat distribution and the risk of BE is unknown. METHODS: We conducted a retrospective case-control study in patients who underwent endoscopy at a single large VA Medical Center between 2000 and 2003. Cases were patients with documented BE who had an abdominal CT scan within 1 yr of the endoscopy, whereas controls were patients without BE (with or without erosive esophagitis) who also had an abdominal CT scan. The surface areas of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were calculated from CT scan images at level of intervertebral disc between L4 and L5, and body mass index (BMI) in kg/m(2) at the time of endoscopy was also recorded. Cases and controls were compared in univariate and multivariable analyses. RESULTS: We identified 36 cases and 93 controls. There were no significant differences between cases and controls in age (mean 63 yr), gender (98% men), or race (71% white Caucasian). BMI was significantly greater in cases than controls (27 vs 24; p= 0.006). BMI > 30 kg/m(2) was associated with a greater risk of BE than lower BMI (odds ratio 4.0; 95% CI: 1.4-11.1, p= 0.008). VAT was approximately 1.5-fold greater in cases than controls (183 vs 115 cm(2); p < 0.0001), whereas SAT was less different (248 vs 200 cm(2); p= 0.03). We estimated that each 10-cm(2) increase in VAT was associated with 9% increase in risk of BE. Interestingly, VAT remained independently associated with BE in the model that adjusted for BMI, and in that model, BMI was not significantly associated with BE. CONCLUSIONS: Obesity seems to be associated with an increased risk of BE. Abdominal visceral adiposity might mediate most of this risk. C1 Houston Dept Vet Affairs Med Ctr, Gastroenterol Sect, Houston, TX USA. Houston Dept Vet Affairs Med Ctr, Sect Hlth Serv Res, Houston, TX USA. Houston Dept Vet Affairs Med Ctr, Dept Radiol, Houston, TX USA. Baylor Coll Med, Dept Med, Houston, TX 77030 USA. RP El-Serag, HB (reprint author), Michael E DeBakey Vet Affairs Med Ctr, 152,2002 Holcombe Blvd, Houston, TX 77030 USA. NR 37 TC 133 Z9 137 U1 1 U2 6 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2005 VL 100 IS 10 BP 2151 EP 2156 DI 10.1111/j.1572-0241.2005.00251.x PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 965KX UT WOS:000231950500004 PM 16181362 ER PT J AU Cheung, RC Currie, S Shen, H Ho, SB Bini, EJ Anand, BS Brau, N Wright, TL AF Cheung, RC Currie, S Shen, H Ho, SB Bini, EJ Anand, BS Brau, N Wright, TL CA VA HCV-001 Study Grp TI Chronic hepatitis C in Latinos: Natural history, treatment eligibility, acceptance, and outcomes SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID VIRUS-INFECTION; RACIAL-DIFFERENCES; UNITED-STATES; VETERANS; THERAPY; RIBAVIRIN; INTERFERON; PREVALENCE AB OBJECTIVES: The natural history of chronic hepatitis C and treatment response are different between blacks and Caucasians, but little comparable data is available about Latinos. METHODS: A cross-sectional secondary analysis to investigate differences between 421 anti-HCV-positive, treatment-naive, HCV-viremic Latinos and 2,510 Caucasians in 24 VA medical centers enrolled in a prospective study. RESULTS: Latinos were infected at a younger age and were less likely to have blood contact during combat, surgery, and needle stick injury, but were more frequently HIV coinfected (20.4%vs 3.9%, p < 0.0001) and prior HAV infection (39.9%vs 26.4%, p= 0.0001). Latinos were more likely to be treatment candidates, but less likely to actually initiate treatment. Liver histology (123 Latinos, 743 Caucasians) showed no difference in fibrosis or fibrosis rate, but steatosis (54.7%vs 43.2%, p= 0.038) was more common in Latinos. Eighty-eight Latinos and 481 Caucasians were subsequently treated with interferon-ribavirin: body mass index (BMI), duration of infection, baseline tests, liver histology and genotype distribution were similar. Compared with Caucasians, Latinos discontinued treatment prematurely more often (39.8%vs 28.9%, p= 0.043) and tended to have lower sustained virological response (SVR) rates (14.8%vs 22.5%, p= 0.10). Multivariate analysis found Latino race and history of recent alcohol use to be associated with early treatment discontinuation, whereas genotype and viral load but not ethnicity to be associated with SVR. CONCLUSIONS: Latinos were infected younger, more frequently HIV coinfected, more likely to meet criteria for antiviral therapy yet less likely to initiate treatment and had a trend toward lower SVR rates than Caucasians, but not in severity of liver disease. Latino ethnicity was associated with early discontinuation but not as an independent predictor of SVR. C1 VA Palo Alto HCS, Div Gastroenterol & Hepatol, Palo Alto, CA 94304 USA. Stanford Univ, Sch Med, Palo Alto, CA 94304 USA. VA Med Ctr, San Francisco, CA USA. VA Med Ctr, Minneapolis, MN USA. VA Med Ctr, New York, NY USA. VA Med Ctr, Houston, TX USA. VA Med Ctr, Bronx, NY USA. RP Cheung, RC (reprint author), VA Palo Alto HCS, Div Gastroenterol & Hepatol, 154C,3801 Miranda Ave, Palo Alto, CA 94304 USA. NR 22 TC 51 Z9 51 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2005 VL 100 IS 10 BP 2186 EP 2193 DI 10.1111/j.1572-0241.2005.00240.x PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 965KX UT WOS:000231950500009 PM 16181367 ER PT J AU Auslander, JN Lieberman, DA Sonnenberg, A AF Auslander, JN Lieberman, DA Sonnenberg, A TI Lack of seasonal variation in the endoscopic diagnoses of Crohn's disease and ulcerative colitis SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; HOSPITAL ADMISSIONS; COLORECTAL-CANCER; UNITED-STATES; EXACERBATIONS; PERIODICITY; COLONOSCOPY; MORTALITY; SCOTLAND; RELAPSE AB BACKGROUND: Conflicting data have been reported about the seasonal variation of inflammatory bowel diseases (IBD). The purpose of the present analysis was to assess the occurrence of seasonal variations in the endoscopic diagnosis of Crohn's disease (CD) and ulcerative colitis (UC). METHODS: The Clinical Outcomes Research Initiative (CORI) uses a computerized endoscopic report generator to collect endoscopic data from 73 diverse practice sites throughout the United States. We utilized the CORI database to analyze the date-specific occurrence of colonoscopy, as well as the colonoscopic diagnoses of CD and UC. Time trends were analyzed by autocorrelation, linear, and nonlinear regression. RESULTS: Between January 2000 and December 2003, the number of colonoscopies increased 4.1-fold. The proportion of colonoscopies with a CD diagnosis fell by 28%, and the proportion of colonoscopies with a UC diagnosis fell by 50%. The occurrence of neither CD nor UC was shaped by any clear-cut seasonal periodicity. However, the trends of the two diseases revealed strikingly similar patterns with four resembling peaks superimposed on their monthly fluctuations. CONCLUSIONS: Endoscopic diagnosis of IBD is unaffected by any seasonal variation. The decline in the diagnostic rate of colonic IBD may reflect a relative increase in the utilization of colonoscopy for colon cancer screening. The similarity in the monthly fluctuations of both IBD suggests that their incidence or flare-ups may be influenced by identical exogenous risk factors. C1 Portland VA Med Ctr, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Portland, OR USA. RP Sonnenberg, A (reprint author), Portland VA Med Ctr, P3-GI,3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. FU NIDDK NIH HHS [2-U01-DK057132-06A1, 5-R33-DK061778-03] NR 29 TC 17 Z9 17 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2005 VL 100 IS 10 BP 2233 EP 2238 DI 10.1111/j.1572-0241.2005.50127.x PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 965KX UT WOS:000231950500017 PM 16181375 ER PT J AU Spiegel, BMR Kanwal, F Naliboff, B Mayer, E AF Spiegel, BMR Kanwal, F Naliboff, B Mayer, E TI The impact of somatization on the use of gastrointestinal health-care resources in patients with irritable bowel syndrome SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID QUALITY-OF-LIFE; SOMATIC SYMPTOMS; DISORDERS; COSTS; WOMEN AB BACKGROUND: It is unclear why patients with irritable bowel syndrome (IBS) consume a disproportionate amount of health-care resources versus matched controls. One possibility is the presence of comorbid somatization-a process marked by multiple unexplained somatic complaints that is highly prevalent in IBS. We sought to determine whether higher levels of somatization are associated with higher levels of gastrointestinal (GI) resource utilization in IBS. METHODS: A total of 1,410 patients > 18 yr with IBS were evaluated at a university-based clinic. Subjects completed a symptom questionnaire, the SCL-90R psychometric checklist, and the SF-36 Health Survey. We measured two outcomes: (1) a 1-yr direct GI health-care costs and (2) a 1-yr number of GI physician visits. Our primary regressor was somatization as measured by the somatization subscale of the SCL-90R. We performed regression analyses to measure the adjusted influence of somatization on GI resource utilization. RESULTS: In the full sample of patients, there were no differences in the likelihood of expending versus not expending previous GI health-care costs among groups with varying levels of somatization. Similarly, there were no differences in either the likelihood of visiting a GI physician or the number of overall physician visits among patients with varying levels of somatization. However, in the subset of patients expending at least $1.00 in GI costs in the previous year (53% of cohort), there was a significantly higher cost of care for subjects with high versus low levels of somatization. CONCLUSIONS: IBS patients with high levels of somatization are not more likely to seek GI care compared to patients with low levels of somatization. However, once they are evaluated for care, patients with high somatization expend significantly more GI health-care costs. This suggests that somatization is positively associated with health-care costs in IBS, and that the association may be driven more by physicians than patients. C1 VA Greater Los Angeles Healthcare Syst, Div Gastroenterol, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Div Digest Dis, Los Angeles, CA 90073 USA. Ctr Study Digest Healthcare Qual & Outcome, CURE Digest Dis Res Ctr, Los Angeles, CA 90073 USA. Ctr Neurovisceral Sci & Womens Hlth, Los Angeles, CA USA. RP Spiegel, BMR (reprint author), VA Greater Los Angeles Healthcare Syst, Div Gastroenterol, 11301 Wilshire Blvd,Bldg 115,Room 215E, Los Angeles, CA 90073 USA. FU NCCIH NIH HHS [1 R24 AT002681]; NIDDK NIH HHS [P50 DK-64539, R01 DK-07768, R01 DK-48351] NR 33 TC 36 Z9 37 U1 5 U2 6 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2005 VL 100 IS 10 BP 2262 EP 2273 DI 10.1111/j.1572-0241.2005.00269.x PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 965KX UT WOS:000231950500021 PM 16181379 ER PT J AU Weintraub, D Stern, MB AF Weintraub, D Stern, MB TI Psychiatric complications in Parkinson disease SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Review ID DRUG-INDUCED PSYCHOSIS; PLACEBO-CONTROLLED TRIAL; NURSING-HOME PLACEMENT; COGNITIVE IMPAIRMENT; RISK-FACTORS; LEWY BODIES; VISUAL HALLUCINATIONS; ALZHEIMERS-DISEASE; DEPRESSION; DEMENTIA AB Although Parkinson disease (PD) is primarily considered a movement disorder, the high prevalence of psychiatric complications suggests that it is more accurately conceptualized as a neuropsychiatric disease. Affective disorders, cognitive impairment, and psychosis are particularly common in PD and are associated with excess disability, worse quality of life, poorer outcomes, and caregiver distress. Yet, in spite of this and their frequent occurrence, there is incomplete understanding of the epidemiology, phenomenology, risk factors, neuropathophysiology, and optimal treatment strategies for these disorders, Psychiatric complications are typically comorbid, and there is great intra- and inter-individual variability in presentation. The hallmark neuropathophysiological changes that occur in PD plus the association between exposure to dopaminergic medications and certain psychiatric disorders suggest a neurobiological basis for most psychiatric symptoms, although psychological factors are probably involved in the development of affective disorders. Although antidepressants, antipsychotics, and cognition-enhancing agents are commonly prescribed in PD, controlled studies demonstrating efficacy and tolerability of these drugs are virtually nonexistent, Because of the high prevalence and complexity of psychiatric complications in PD, geriatric psychiatrists are in a position to offer valuable consultation and clinical care to this population. This article provides an overview of the epidemiology, pathophysiology, clinical presentation, and management of the most common psychiatric complications in PD. C1 Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Neurol, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, PADRECC, Parkinsons Dis Res Educ & Clin Ctr, Philadelphia, PA USA. MIRECC, Philadelphia, PA USA. RP Weintraub, D (reprint author), 3535 Market St,Room 3003, Philadelphia, PA 19104 USA. EM weintrau@mail.med.upenn.edu FU NIMH NIH HHS [K23MH067894] NR 78 TC 72 Z9 74 U1 0 U2 4 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD OCT PY 2005 VL 13 IS 10 BP 844 EP 851 DI 10.1176/appi.ajgp.13.10.844 PG 8 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 972TK UT WOS:000232475900003 PM 16223962 ER PT J AU Husain, MM Rush, AJ Sackeim, HA Wisniewski, SR McClintock, SM Craven, N Holiner, J Mitchell, JR Balasubramani, GK Hauger, R AF Husain, MM Rush, AJ Sackeim, HA Wisniewski, SR McClintock, SM Craven, N Holiner, J Mitchell, JR Balasubramani, GK Hauger, R TI Age-related characteristics of depression - A preliminary STAR*D report SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article; Proceedings Paper CT 17th Annual Meeting of the American-Association-for-Geriatric-Psychiatry CY FEB 21-25, 2004 CL Baltimore, MD SP Amer Assoc Geriatr Psychiat ID SEQUENCED TREATMENT ALTERNATIVES; MAJOR DEPRESSION; SYMPTOMATOLOGY IDS; RATING SCALE; INVENTORY; SYMPTOMS; OUTPATIENTS; DISORDERS; ILLNESS; RATIONALE AB Objective: Studies have shown that age is a determinant in the course of major depressive disorder Age has been associated with depression severity; it has also been associated with varying depressive symptomatology The authors explore the relationships between current age and depression severity, course of illness, presenting symptom features, and comorbid symptoms. Methods: Baseline clinical and sociodemographic information was collected on 1, 498 participants enrolled in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) Study. Five age cohorts (1825, 26-35, 36-50,51-65, and 66-75) were compared on both sociodemographic and clinical factors. Depressive symptoms were measured with the 30-item clinician-rated Inventory of Depressive symptomatology Results: Clinically meaningful differences were found among age cohorts on several clinical and depressive symptom features. Older patients (51-65 and 66-75) endorsed longer durations of illness, more major depressive episodes, a later age at onset of their first major depressive episode, and more general medical comorbidities. Older patients had more middle and terminal insomnia, less irritability, and less hypersomnia. They were less likely to hold negative views of themselves or of their future and were less likely to report previous suicide attempts. Older patients were less likely to endorse symptoms consistent with generalized anxiety disorder, social phobia, panic disorder, and drug abuse. Conclusions: These cross-sectional data indicate that different age-cohorts present with varying sociodemographic and clinical characteristics, as well as general-medical and psychiatric comorbid conditions. C1 Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX 75230 USA. New York State Psychiat Inst & Hosp, New York, NY 10032 USA. Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Epidemiol Data Ctr, Pittsburgh, PA 15260 USA. Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. Laureate Psychiat Clin & Hosp, Tulsa, OK USA. RP Husain, MM (reprint author), SW Med Sch, Dept Psychiat, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM husain@utsouthwestern.edu OI Wisniewski, Stephen/0000-0002-3877-9860; Rush, Augustus/0000-0003-2004-2382; Goundappa K, Balasubramani/0000-0001-7221-1825 FU NIMH NIH HHS [N01MH90003] NR 34 TC 32 Z9 32 U1 1 U2 4 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD OCT PY 2005 VL 13 IS 10 BP 852 EP 860 DI 10.1176/appi.ajgp.13.10.852 PG 9 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 972TK UT WOS:000232475900004 PM 16223963 ER PT J AU LaMontagne, AD Stoddard, AM Youngstrom, RA Lewiton, M Sorensen, G AF LaMontagne, AD Stoddard, AM Youngstrom, RA Lewiton, M Sorensen, G TI Improving the prevention and control of hazardous substance exposures: A randomized controlled trial in manufacturing worksites SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE intervention research; intervention effectiveness research; experimental design; evaluation; upstream prevention; hazardous substances; precautionary principle ID MINNESOTA WOOD DUST; INTERVENTION EFFECTIVENESS; OCCUPATIONAL-HEALTH; UNITED-STATES; PROGRAMS; SAFETY; WELLWORKS-2 AB Background New measures of exposure prevention (EP) activity were used to evaluate the effectiveness of a 16-month management focused intervention addressing hazardous substance exposures in manufacturing work settings. Methods EP efforts were assessed using a rating scheme developed for this study. The rating scheme yields a set of measures of exposure potential and protection, which are combined into an overall EP summary rating. A randomized, controlled design was used to assess intervention effectiveness. Fifteen large manufacturing worksites completed the 16-month intervention and follow-up assessments. Analyses were conducted on the 107 production processes assessed at both baseline and final. Results Patterns of improvement within the intervention condition were consistent with the intervention emphasis on upstream orsource focused intervention; whereas patterns in controls were consistent with prevalent practice (more downstream, worker focused). A mixed model analysis of variance showed greater improvement in EP ratings in intervention versus controls, but the difference in improvement was moderate and statistically non-significant. Conclusions This study has demonstrated that EP efforts in the manufacturing sector can be systematically assessed across the full range of hazardous substances in use, and that such assessments can serve both needs assessment and effectiveness evaluation functions. Findings suggest that more sustained or intense management focused intervention would significantly improve EP activity in manufacturing settings. C1 Univ Melbourne, Ctr Hlth & Soc, Sch Populat Hlth, Melbourne, Vic 3010, Australia. Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. New England Res Inst, Watertown, MA 02172 USA. Mass Dept Labor & Workforce Dev, Div Occupat Safety, On Site Consultat Program, W Newton, MA USA. Harvard Univ, Sch Publ Hlth, Dept Hlth & Social Behav, Boston, MA 02115 USA. RP LaMontagne, AD (reprint author), Univ Melbourne, Ctr Hlth & Soc, Sch Populat Hlth, 207 Bouverie St,Level 4, Melbourne, Vic 3010, Australia. EM alamonta@unimelb.edu.au FU NCI NIH HHS [5 R01 CA68087]; NIOSH CDC HHS [5 R01 OH04012] NR 31 TC 9 Z9 9 U1 1 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD OCT PY 2005 VL 48 IS 4 BP 282 EP 292 DI 10.1002/ajim.20218 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 971BR UT WOS:000232356600005 PM 16142731 ER PT J AU Newsome, BB Warnock, DG Kiefe, CI Weissman, NW Houston, TK Centor, RM Person, SD McClellan, WM Allison, JJ AF Newsome, BB Warnock, DG Kiefe, CI Weissman, NW Houston, TK Centor, RM Person, SD McClellan, WM Allison, JJ TI Delay in time to receipt of thrombolytic medication among Medicare patients with kidney disease SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE kidney; reperfusion; coronary disease ID ACUTE MYOCARDIAL-INFARCTION; COOPERATIVE CARDIOVASCULAR PROJECT; ACUTE CORONARY SYNDROMES; STAGE RENAL-DISEASE; QUALITY-OF-CARE; ELDERLY-PATIENTS; INSUFFICIENCY; OUTCOMES; THERAPY; ANGIOPLASTY AB Background Patients with kidney disease and acute myocardial infarction (AMI) receive standard therapy, including thrombolytic medication, less frequently than patients with normal kidney function. Our goal is to identify potential differences in thrombolytic medication delays and thrombolytic-associated bleeding events by severity of kidney disease. Methods: This is a retrospective cohort analysis of Cooperative Cardiovascular Project data for all Medicare patients with AMI from 4,601 hospitals. Outcome measures included time to administration of thrombolytic medication censored at 6 hours and bleeding events. Results. Of 109,169 patients (mean age, 77.4 years; 50.6% women), 13.9% received thrombolysis therapy. Average time to thrombolytic therapy was longer in patients with worse kidney function. Adjusted hazard ratios for minutes to thrombolytic therapy were 0.83 (95% confidence interval [CI], 0.79 to 0.87) for patients with a serum creatinine level of 1.6 to 2.0 mg/dL (141 to 177 mu mol/L) and 0.58 (95% Cl, 0.53 to 0.63) for patients with a creatinine level greater than 2.0 mg/dL (>177 mu mol/L) or on dialysis therapy compared with those with normal kidney function. Odds ratios for bleeding events in patients administered thrombolytics versus those who were not decreased with worse kidney function: adjusted odds ratios, 2.28 (95% Cl, 2.16 to 2.42) in patients with normal kidney function and 1.84 (95% Cl, 1.09 to 3.10) in dialysis patients. Conclusion: Patients with worse kidney function experienced treatment delays, but were not at greater risk for thrombolysis-associated excess bleeding events. Physician concerns of thrombolytic-associated bleeding may not be sufficient reason to delay the administration of thrombolytic medication. C1 Ctr Outcomes & Effectiveness Res & Educ, Dept Med, Div Nephrol, Birmingham, AL USA. Ctr Outcomes & Effectiveness Res & Educ, Dept Med, Div Prevent Med, Birmingham, AL USA. Ctr Outcomes & Effectiveness Res & Educ, Div Gen Internal Med, Birmingham, AL USA. Birmingham Vet Affairs Med Ctr, Dept Med, Div Prevent Med, Birmingham, AL USA. Birmingham Vet Affairs Med Ctr, Dept Med, Div Gen Internal Med, Birmingham, AL USA. Dept Hlth Serv Adm, Birmingham, AL USA. Univ Alabama Birmingham, Birmingham, AL USA. Georgia Med Care Fdn, Atlanta, GA USA. Emory Univ, Sch Med, Dept Med, Div Renal, Atlanta, GA USA. RP Newsome, BB (reprint author), 1530 3rd Ave S,MT 401E2, Birmingham, AL 35294 USA. EM bnewsome@uab.edu RI Houston, Thomas/F-2469-2013; OI Allison, Jeroan/0000-0003-4472-2112 FU AHRQ HHS [T32 HS013852]; NHLBI NIH HHS [R01 HL70786]; None [HS013852] NR 30 TC 3 Z9 3 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 EI 1523-6838 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD OCT PY 2005 VL 46 IS 4 BP 595 EP 602 DI 10.1053/j.ajkd.2005.06.008 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 993DQ UT WOS:000233933300004 PM 16183413 ER PT J AU Pober, BR Lin, A Russell, M Ackerman, KG Chakravorty, S Strauss, B Westgate, MN Wilson, J Donahoe, PK Holmes, LB AF Pober, BR Lin, A Russell, M Ackerman, KG Chakravorty, S Strauss, B Westgate, MN Wilson, J Donahoe, PK Holmes, LB TI Infants with bochdalek diaphragmatic hernia: Sibling precurrence and monozygotic twin discordance in a hospital-based malformation surveillance program SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE congenital diaphragmatic hernia; discordant monozygotic twins; precurrence risk; review ID PRENATAL-DIAGNOSIS; CHROMOSOME-ANOMALIES; UNILATERAL AGENESIS; FAMILIAL OCCURRENCE; CANDIDATE REGION; NEWBORN-INFANTS; BIRTH-DEFECTS; CLEFT-LIP; SIBS; MUTATIONS AB Congenital diaphragmatic hernia (CDH) is a common and often devastating birth defect. In order to learn more about possible genetic causes, we reviewed and classified 203 cases of the Bochdalek hernia type identified through the Brigham and Women's Hospital (BWH) Active Malformation Surveillance Program over a 28-year period. Phenotypically, 55% of the cases had isolated CDH, and 45% had complex CDH defined as CDH in association with additional major malformations or as part of a syndrome. When classified according to likely etiology, 17% had a Recognized Genetic etiology for their CDH, while the remaining 83% had No Apparent Genetic etiology. Detailed analysis using this largest cohort of consecutively collected cases of CDH showed low precurrence among siblings. Additionally, there was no concordance for CDH among five monozygotic twin pairs. These findings, in conjunction with previous reports of de novo dominant mutations in patients with CDH, suggest that new mutations may be an important mechanism responsible for CDH. The twin data also raise the possibility that epigenetic abnormalities contribute to the development of CDH. (c) 2005 Wiley-Liss, Inc. C1 Childrens Hosp, Dept Surg, Boston, MA 02115 USA. MassGen Gen Hosp Children, Boston, MA USA. Brigham & Womens Hosp, Malformat Surveillance Program, Boston, MA 02115 USA. MassGen Hosp Children, Pediat Surg Serv, Boston, MA USA. MassGen Hosp Children, Pediat Surg Res Labs, Boston, MA USA. Childrens Hosp, Dept Med, Div Emergency Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA. RP Pober, BR (reprint author), Childrens Hosp, Dept Surg, 300 Longwood Ave,Fegan 325, Boston, MA 02115 USA. EM Barbara.pober@childrens.harvard.edu FU NHLBI NIH HHS [K08 HL076286]; NICHD NIH HHS [R01 HD055150, P01 HD039942, R01 HD055150-01, P01 HD 39942-03]; ODCDC CDC HHS [U50/CCU 1132247-03] NR 92 TC 41 Z9 41 U1 0 U2 0 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 81 EP 88 DI 10.1002/ajmg.a.30904 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 969MV UT WOS:000232239200001 PM 16094667 ER PT J AU Henderson, MC Meyers, FJ Tierney, LM AF Henderson, MC Meyers, FJ Tierney, LM TI Confronting the brutal facts in health care SO AMERICAN JOURNAL OF MEDICINE LA English DT Editorial Material ID MEDICINE; FUTURE C1 Univ Calif Davis, Med Ctr, Sacramento, CA 95817 USA. Alliance Acad Internal Med, Washington, DC USA. US Dept Vet Affairs, Med Ctr, San Francisco, CA USA. RP Henderson, MC (reprint author), Univ Calif Davis, Med Ctr, Sacramento, CA 95817 USA. NR 32 TC 6 Z9 6 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD OCT PY 2005 VL 118 IS 10 BP 1061 EP 1063 DI 10.1016/j.amjmed.2005.08.003 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 972SA UT WOS:000232472300001 PM 16194632 ER PT J AU Stelfox, HT Gandhi, TK Orav, EJ Gustafson, ML AF Stelfox, HT Gandhi, TK Orav, EJ Gustafson, ML TI The relation of patient satisfaction with complaints against physicians and malpractice lawsuits SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE malpractice; satisfaction; complaints; patient safety ID HOSPITAL QUALITY; CLAIMS HISTORY; CARE; EXPERIENCE; JUDGMENTS; SURGEONS AB PURPOSE: A small number of physicians generate a disproportionate share of complaints front patients and of malpractice lawsuits. If these grievances relate to patients' dissatisfaction with care, it might be possible to use commonly distributed patient satisfaction Surveys to identify physician,, at high risk of complaints from patients and of malpractice lawsuits, We sought to examine associations among patients' satisfaction survey ratings of physicians' performance and complaints from patient, risk management episodes, and rates of malpractice lawsuits. SUBJECTS AND METHODS: We examined 353 physicians at a large US teaching hospital whose inpatient performance was rated by 10 or more patients between January 1. 2001. and March 31. 2003. Physicians were divided into 3 tertiles according to satisfaction on a commercial survey instrument administered to recently discharged patients. Records of unsolicited complaints from patients (January 1. 2000. to March 31. 2003) and risk management episodes (January 1. 1983. to March 31. 2003) were analyzed after adjusting for the physician's specialty and panel characteristics of the physician's patients. RESULTS: Decreases in physicians' patient satisfaction survey scores from the highest to the lowest tertile were associated with increased rates of unsolicited complaints from patients (200 vs 243 vs 492 complaints per 100 000 patient discharges: P < 0.0001 and risk management episodes (29 vs 43 vs 56 risk management episodes per 100 000 patient discharges: P = 0.007). Compared with physicians with the top satisfaction survey ratings, physicians in the middle tertile had malpractice lawsuit rates that were 26% higher (rate ratio [RR] = 1.26; 95% confidence interval [CI]: 0.72 to 2.18: P = 0.41). and physicians in the bottom tertile had malpractice lawsuit rates that were 110% higher (RR 2.10;. 95% CI: 1.13 to 3.90): P = 0.019). CONCLUSION: Patient satisfaction survey ratings of inpatient physicians' performance are associated with complaints from patients and with risk management episodes. Commonly distributed patient satisfaction surveys may be useful quality improvement tools. but identifying physicians at high risk of complaints from patients and of malpractice lawsuits remains challenging. (c) 2005 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Brigham & Womens Hosp, Div Gen Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. Brigham & Womens Hosp, Ctr Clin Excellence, Boston, MA 02115 USA. RP Stelfox, HT (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Fruit St,Clin 309, Boston, MA 02114 USA. EM hstelfox@partners.org NR 28 TC 79 Z9 79 U1 3 U2 9 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD OCT PY 2005 VL 118 IS 10 BP 1126 EP 1133 DI 10.1016/j.amjmed.2005.01.060 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 972SA UT WOS:000232472300013 PM 16194644 ER PT J AU Mullins, ME Lev, MH Schellingerhout, D Gonzalez, RG Schaefer, PW AF Mullins, ME Lev, MH Schellingerhout, D Gonzalez, RG Schaefer, PW TI Intracranial hemorrhage complicating acute stroke: How common is hemorrhagic stroke on initial head CT scan and how often is initial cliniclal diagnosis of acute stroke eventually confirmed? SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID ACUTE ISCHEMIC-STROKE; SUBARACHNOID HEMORRHAGE; COMPUTED-TOMOGRAPHY; MRI; TRANSFORMATION; RISK; TOOL AB BACKGROUND AND PURPOSE: Assessment of possible hemorrhage in acute stroke before appropriate therapy remains important. The aim of this study was to determine the frequency with which patients present with clinical stroke and have intracranial hemorrhage on initial noncontrast head CT scan (NCCT). In addition, we sought to determine the frequency with which initial clinical diagnosis acute stroke is confirmed in this group. METHODS: Medical records of 691 consecutive patients with admitting diagnosis of acute stroke were evaluated retrospectively. Results of initial NCCT performed within 24 hours after presentation were assessed. All patients were examined before anticoagulation or thrombolysis. Correlation with treatment and leading differential etiology was made. RESULTS: Twenty-five patients (25/691 [3.6%]) had hemorrhage. Twenty-three patients (23/25 [92%]) had intraparenchymal hemorrhage only. One patient (1/25 [4%]) had a combination of intraparenchymal and subarachnoid hemorrhage. One patient (1/25 [4%]) had subdural hemorrhage only. Twenty-two NCCT scans (22/25 [88%]) were performed within 6 hours of presentation. Seventeen NCCT scans (17/25 [68%]) were performed within 3 hours of presentation. CONCLUSION. Despite frequent concerns for intracranial hemorrhage complicating acute stroke and treatment, a low percentage of patients had this complication. Moreover, our frequency is much lower than the wide ranges reported elsewhere. The most common type of intracranial hemorrhage in this cohort was intraparenchymal, but subarachnoid and subdural hemorrhages were also diagnosed and must also be considered. Twenty-eight percent of patients with initial suspicion of acute ischemic stroke are eventually given other diagnoses. These results may have implications for use of CT imaging. C1 Massachusetts Gen Hosp, Div Neuroradiol, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Texas, SW Med Sch, Houston, TX 77030 USA. RP Mullins, ME (reprint author), Massachusetts Gen Hosp, Div Neuroradiol, Dept Radiol, GRB 285,55 Fruit St, Boston, MA 02114 USA. NR 27 TC 7 Z9 7 U1 0 U2 1 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 2207 EP 2212 PG 6 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 973UJ UT WOS:000232547800008 PM 16219823 ER PT J AU Cavallerano, JD Aiello, LP Cavallerano, AA Katalinic, P Hock, K Kirby, R Aiello, LM AF Cavallerano, JD Aiello, LP Cavallerano, AA Katalinic, P Hock, K Kirby, R Aiello, LM CA Joslin Vision Network Clinical TI Nonmydriatic digital Imaging alternative for annual retinal examination in persons with previously documented no or mild diabetic retinopathy SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article; Proceedings Paper CT 8th Annual Meeting of the American-Telemedicine-Association CY APR 27-30, 2003 CL Orlando, FL SP Amer Telemed Assoc ID EYE CARE; PROGRAM; OPHTHALMOSCOPY; MELLITUS AB PURPOSE: To prospectively evaluate the Joslin Vision Network (JVN) for follow,up annual retinal examination for level of diabetic retinopathy (DR). DESIGN: Prospective cohort study. METHODS: Fifty-two patients with no or mild nonproliferative DR (Early Treatment Diabetic Retinopathy Study [ETDRS] level :535) and no diabetic macular edema (DME) at dilated retinal examination 11 or more months earlier were imaged. Patients then had dilated retinal examination and color 35,mm seven standard field stereoscopic photography (ETDRS photographs) and completed a satisfaction survey. Level of DR determined from JVN images, clinical examination, and ETDRS photographs was compared. RESULTS: Two (1.9%) eyes had JVN images ungradable for level of DR. In the 102 gradable eyes (98.1%), JVN diagnosis exactly matched clinical examination for level of DR in 82 eyes (77.9%) and was within one level of DR in all eyes (100%). Three eyes (2.9%) had JVN images ungradable for DME; one of these eyes had DME by clinical examination. JVN diagnosis matched clinical examination for DME in all eyes (101) gradable by JVN. Fifty patients (96.1%) reported JVN imaging improved their understanding of eye disease, 100% were satisfied with JVN, and forty-eight (92.3%) would consider replacing dilated examination by their eye doctor with JVN imaging. CONCLUSIONS: JVN digital imaging closely matched clinical examination for level of DR and DME, would have resulted in no patients receiving less stringent follow-up, and was well accepted by patients. JVN digital imaging may be a suitable alternative for annual dilated retinal examination for determining level of DR or DME and appropriate follow-up comprehensive ophthalmic examination. (c) 2005 by Elsevier Inc. All rights reserved. C1 Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02115 USA. RP Aiello, LP (reprint author), Joslin Diabet Ctr, Beetham Eye Inst, 1 Joslin Pl, Boston, MA 02215 USA. EM Lloyd.m.aiello@joslin.harvarcl.edu NR 18 TC 23 Z9 23 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD OCT PY 2005 VL 140 IS 4 BP 667 EP 673 DI 10.1016/j.ajo.2005.03.075 PG 7 WC Ophthalmology SC Ophthalmology GA 975YD UT WOS:000232699100013 PM 16083842 ER PT J AU Siebens, H Andres, PL Ni, PS Coster, WJ Haley, SM AF Siebens, H Andres, PL Ni, PS Coster, WJ Haley, SM TI Measuring physical function in patients with complex medical and postsurgical conditions - A computer adaptive approach SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Article DE rehabilitation; outcomes research; activities of daily living ID POST-ACUTE CARE; HEALTH-STATUS ASSESSMENT; OUTCOMES; HOSPITALIZATION; DISABILITY; ADULTS; TRIAL AB Siebens H, Andres PL, Pensheng N, Coster WJ, Haley SM: Measuring physical function in patients with complex medical and postsurgical conditions: a computer adaptive approach. Am J Phys Med Rehabil 2005;84:741-748. Objective: To examine whether the range of disability in the medically complex and postsurgical populations receiving rehabilitation is adequately sampled by the new Activity Measure - Post-Acute Care (AMPAC), and to assess whether computer adaptive testing (CAT) can derive valid patient scores using fewer questions. Design: Observational study of 158 subjects (mean age 67.2 yrs) receiving skilled rehabilitation services in inpatient (acute rehabilitation hospitals, skilled nursing facility units) and community (home health services, outpatient departments) settings for recent-onset or worsening disability from medical (excluding neurological) and surgical (excluding orthopedic) conditions. Measures were interviewer-administered activity questions (all patients) and physical functioning portion of the SF-36 (outpatients) and standardized chart items (11 Functional Independence Measure (FIM (TM)), 19 Standardized Outcome and Assessment Information Set (OASIS) items, and 22 Minimum Data Set (MDS) items). Rasch modeling analyzed all data and the relationship between person ability estimates and average item difficulty. CAT assessed the ability to derive accurate patient scores using a sample of questions. Results: The 163-item activity item pool covered the range of physical movement and personal and instrumental activities. CAT analysis showed comparable scores between estimates using 10 items or the total item pool. Conclusion: The AM-PAC can assess a broad range of function in patients with complex medical illness. CAT achieves valid patient scores using fewer questions. C1 Univ Virginia, Dept Phys Med & Rehabil, Charlottesville, VA 22903 USA. Massachusetts Gen Hosp, MGH Neurol Clin Trials Unit, Boston, MA 02114 USA. Boston Univ, Hlth Disabil Res Inst, Boston, MA 02215 USA. Boston Univ, Coll Hlth & Rehabil, Dept Rehabil Sci, Boston, MA 02215 USA. RP Siebens, H (reprint author), 13650 Del Monte Dr 21B, Seal Beach, CA 90740 USA. FU NICHD NIH HHS [R01 HD43568]; PHS HHS [H133B990005] NR 32 TC 19 Z9 19 U1 3 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0894-9115 J9 AM J PHYS MED REHAB JI Am. J. Phys. Med. Rehabil. PD OCT PY 2005 VL 84 IS 10 BP 741 EP 748 DI 10.1097/01.phm.0000186274.08468.35 PG 8 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 970CH UT WOS:000232282300003 PM 16205429 ER PT J AU Ho, RC Hirshman, MF Li, YF Cai, DS Farmer, JR Aschenbach, WG Witczak, CA Shoelson, SE Goodyear, LJ AF Ho, RC Hirshman, MF Li, YF Cai, DS Farmer, JR Aschenbach, WG Witczak, CA Shoelson, SE Goodyear, LJ TI Regulation of I kappa B kinase and NF-kappa B in contracting adult rat skeletal muscle SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE exercise; p38; ERK; AMPK signaling ID JUN NH2-TERMINAL KINASE; SIGNALING PATHWAY; GENE-EXPRESSION; P38 MAPK; TRANSCRIPTION FACTOR; DEPENDENT MANNER; MESSENGER-RNA; EXERCISE; ACTIVATION; INTERLEUKIN-6 AB Regulation of I kappa B kinase and NF-kappa B in contracting adult rat skeletal muscle. Am J Physiol Cell Physiol 289: C794-C801, 2005. First published May 11, 2005; doi:10.1152/ajpcell.00632.2004. - Nuclear factor-kappa B (NF-kappa B) is a transcription factor with important roles in regulating innate immune and inflammatory responses. NF-kappa B is activated through the phosphorylation of its inhibitor, I kappa B, by the I kappa B kinase (IKK) complex. Physical exercise elicits changes in skeletal muscle gene expression, yet signaling cascades and transcription factors involved remain largely unknown. To determine whether NF-kappa B signaling is regulated by exercise in vivo, rats were run on a motorized treadmill for 5 - 60 min. Exercise resulted in up to twofold increases in IKK alpha/beta phosphorylation in the soleus and red gastrocnemius muscles throughout the time course studied. In red gastrocnemius muscles, NF-kappa B activity increased 50% 1 - 3 h after 60 min of treadmill exercise, returning to baseline by 5 h. Contraction of isolated extensor digitorum longus muscles in vitro increased IKK alpha/beta phosphorylation sevenfold and this was accompanied by a parallel increase in I kappa B alpha phosphorylation. Additional kinases that are activated by exercise include p38, extracellular-signal regulated protein kinase (ERK), and AMP-activated protein kinase ( AMPK). Inhibitors of p38 (SB-203580) and ERK (U-0126) blunted contraction-mediated IKK phosphorylation by 39 +/- 4% (P = 0.06) and 35 +/- 10% (P = 0.09), respectively, and in combination by 76 +/- 5% (P < 0.05), suggesting that these kinases might influence the activation of IKK and NF-kappa B during exercise. In contrast, 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside, an activator of AMPK, had no effect on either IKK or NF-kappa B activity. In conclusion, acute submaximal exercise transiently stimulates NF-kappa B signaling in skeletal muscle. This activation is a local event because it can occur in the absence of exercise-derived systemic factors. C1 Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Goodyear, LJ (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM laurie.goodyear@joslin.harvard.edu FU NIAMS NIH HHS [F32 AR049662, R01-AR45670, R01-AR42238]; NIDDK NIH HHS [R01-DK51729, R01-DK45493] NR 49 TC 79 Z9 85 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD OCT PY 2005 VL 289 IS 4 BP C794 EP C801 DI 10.1152/ajpcell.00632.2004 PG 8 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 963RM UT WOS:000231822000004 PM 15888549 ER PT J AU Hull, RL Watts, MR Kodama, K Shen, ZP Utzschneider, KM Carr, DB Vidal, J Kahn, SE AF Hull, RL Watts, MR Kodama, K Shen, ZP Utzschneider, KM Carr, DB Vidal, J Kahn, SE TI Genetic background determines the extent of islet amyloid formation in human islet amyloid polypeptide transgenic mice SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE islet amyloid; islet amyloid polypeptide; genetic background; beta-cell mass; beta-cell dysfunction; insulin secretion ID DIABETES-MELLITUS; GLUCOSE-TOLERANCE; MOUSE MODEL; JAPANESE-AMERICANS; INSULIN-RESISTANCE; AMYLIN RELEASE; C57BL/6J MICE; PIMA-INDIANS; EXPRESSION; CELLS AB Genetic background is important in determining susceptibility to metabolic abnormalities such as insulin resistance and beta-cell dysfunction. Islet amyloid is associated with reduced beta-cell mass and function and develops in the majority of our C57BL/6J x DBA/2J (F-1) male human islet amyloid polypeptide (hIAPP) transgenic mice after 1 yr of increased fat feeding. To determine the relative contribution of each parental strain, C57BL/6J (BL6) and DBA/2J (DBA2), to islet amyloid formation, we studied male hIAPP mice on each background strain (BL6, n = 13; and DBA2 n = 11) and C57BL/6J x DBA/2J F-1 mice (n = 17) on a 9% (wt/wt) fat diet for 1 yr. At the end of 12 mo, islet amyloid deposition was quantified from thioflavin S-stained pancreas sections. The majority of mice in all groups developed islet amyloid (BL6: 91%, F-1: 76%, DBA2: 100%). However, the prevalence (% amyloid-positive islets; BL6: 14 +/- 3%, F-1: 44 +/- 8%, DBA2: 49 +/- 9%, P < 0.05) and severity (% islet area occupied by amyloid; BL6: 0.03 +/- 0.01%, F-1: 9.2 +/- 2.9%, DBA2: 5.7 +/- 2.3%, p <= 0.01) were significantly lower in BL6 than F1 and DBA2 mice. Increased islet amyloid severity was negatively correlated with insulin-positive area per islet, in F-1 (r(2) = 0.75, P < 0.001) and DBA2 (r(2) = 0.87, P < 0.001) mice but not BL6 mice (r(2) = 0.07). In summary, the extent of islet amyloid formation in hIAPP transgenic mice is determined by background strain, with mice expressing DBA/2J genes ( F1 and DBA2 mice) being more susceptible to amyloid deposition that replaces beta-cell mass. These findings underscore the importance of genetic and environmental factors in studying metabolic disease. C1 Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, Seattle, WA 98108 USA. Univ Washington, Dept Obstet & Gynecol, Div Maternal Fetal Med, Seattle, WA 98195 USA. RP Hull, RL (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Div Metab Endocrinol & Nutr, 151,1660 S Columbian Way, Seattle, WA 98108 USA. EM rhull@u.washington.edu OI Kahn, Steven/0000-0001-7307-9002 FU NCRR NIH HHS [RR-06066]; NHLBI NIH HHS [HL-07028]; NIDDK NIH HHS [DK-17047, DK-50703] NR 45 TC 8 Z9 8 U1 0 U2 1 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 E703 EP E709 DI 10.1152/ajpendo.00471.2004 PG 7 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 962MV UT WOS:000231737800024 PM 15899941 ER PT J AU Li, RL Chase, M Jung, SK Smith, PJS Loeken, MR AF Li, RL Chase, M Jung, SK Smith, PJS Loeken, MR TI Hypoxic stress in diabetic pregnancy contributes to impaired embryo gene expression and defective development by inducing oxidative stress SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE diabetic embryopathy; neural tube; hypoxia; Pax3 ID NEURAL-TUBE DEFECTS; RADICAL SCAVENGING ENZYMES; HIGH GLUCOSE; PAX-3 GENE; CONGENITAL-MALFORMATIONS; SUPEROXIDE-DISMUTASE; METABOLIC CONTROL; FACTOR 1-ALPHA; MOUSE MUTANT; MICE LACKING AB We have shown that neural tube defects (NTD) in a mouse model of diabetic embryopathy are associated with deficient expression of Pax3, a gene required for neural tube closure. Hyperglycemia-induced oxidative stress is responsible. Before organogenesis, the avascular embryo is physiologically hypoxic (2 - 5% O-2). Here we hypothesized that, because O-2 delivery is limited at this stage of development, excess glucose metabolism could accelerate the rate of O-2 consumption, thereby exacerbating the hypoxic state. Because hypoxia can increase mitochondrial superoxide production, excessive hypoxia may contribute to oxidative stress. To test this, we assayed O-2 flux, an indicator of O-2 availability, in embryos of glucose-injected hyperglycemic or saline-injected mice. O-2 flux was reduced by 30% in embryos of hyperglycemic mice. To test whether hypoxia replicates, and hyperoxia suppresses, the effects of maternal hyperglycemia, pregnant mice were housed in controlled O-2 chambers on embryonic day 7.5. Housing pregnant mice in 12% O-2, or induction of maternal hyperglycemia ( > 250 mg/dl), decreased Pax3 expression fivefold, and increased NTD eightfold. Conversely, housing pregnant diabetic mice in 30% O-2 significantly suppressed the effect of maternal diabetes to increase NTD. These effects of hypoxia appear to be the result of increased production of mitochondrial superoxide, as indicated by assay of lipid peroxidation, reduced glutathione, and H2O2. Further support of this interpretation was the effect of antioxidants, which blocked the effects of maternal hypoxia, as well as hyperglycemia, on Pax3 expression and NTD. These observations suggest that maternal hyperglycemia depletes O-2 in the embryo and that this contributes to oxidative stress and the adverse effects of maternal hyperglycemia on embryo development. C1 Joslin Diabet Ctr, Sect Dev & Stem Cell Biol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Marine Biol Lab, BioCurrents Res Ctr, Program Mol Physiol, Woods Hole, MA 02543 USA. RP Loeken, MR (reprint author), Joslin Diabet Ctr, Sect Dev & Stem Cell Biol, 1 Joslin Pl, Boston, MA 02215 USA. EM Mary.loeken@joslin.harvard.edu OI Loeken, Mary/0000-0002-8056-9816 FU NCRR NIH HHS [P41 RR-001395]; NIDDK NIH HHS [R01-DK-58300, R01 DK058300] NR 57 TC 60 Z9 64 U1 0 U2 11 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 E591 EP E599 DI 10.1152/ajpendo.00441.2004 PG 9 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 962MV UT WOS:000231737800010 PM 15928021 ER PT J AU Nareika, A He, L Game, BA Slate, EH Sanders, JJ London, SD Lopes-Virella, MF Huang, Y AF Nareika, A He, L Game, BA Slate, EH Sanders, JJ London, SD Lopes-Virella, MF Huang, Y TI Sodium lactate increases LPS-stimulated MMP and cytokine expression in U937 histiocytes by enhancing AP-1 and NF-kappa B transcriptional activities SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE diabetes mellitus; lactate; lipopolysaccharide; matrix metalloproteinases; nuclear factor-kappa B; activating protein-1; cytokines ID ACTIVATED PROTEIN-KINASES; C-REACTIVE PROTEIN; INSULIN-RESISTANCE; DIABETES-MELLITUS; ATHEROSCLEROSIS RISK; GENE-EXPRESSION; ADIPOSE-TISSUE; MESSENGER-RNA; INFLAMMATION; MACROPHAGES AB The plasma lactate concentration in patients with obesity and type 2 diabetes is often higher than that in nondiabetic individuals. Although it is known that increased lactate concentration is an independent risk factor for developing type 2 diabetes, the underlying mechanisms are not well understood. Because inflammation plays an important role in the development of type 2 diabetes, we postulated that increased lactate level might contribute to the pathogenesis of type 2 diabetes by enhancing inflammation. In the present study, we demonstrated that preexposure of U937 macrophage-like cells to sodium lactate increased LPS-stimulated matrix metalloproteinase (MMP)-1, IL-1 beta, and IL-6 secretion. Augmentation of LPS-stimulated MMP-1 secretion was diminished when sodium lactate was replaced by lactic acid that reduced pH in the culture medium. Furthermore, quantitative real-time PCR indicated that the increased secretion of MMP-1, IL-1 beta, and IL-6 was due to increased mRNA expression. To explore the underlying signaling mechanism, blocking studies using specific inhibitors for NF-kappa B and MAPK cascades were performed. Results showed that blocking of either NF-kappa B or MAPK pathways led to the inhibition of MMP-1, IL-1 beta, and IL- 6 expression stimulated by sodium lactate, LPS, or both. Finally, electrophoretic mobility shift assays showed a synergy between sodium lactate and LPS on AP-1 and NF-kappa B transcriptional activities. In conclusion, this study has demonstrated for the first time that sodium lactate and LPS exert synergistic effect on MMP and cytokine expression through NF-kappa B and MAPK pathways and revealed a novel mechanism potentially involved in the development of type 2 diabetes and its complications. C1 Med Univ S Carolina, Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29403 USA. Med Univ S Carolina, Dept Med, Div Endocrinol Diabet & Med Genet, Charleston, SC 29403 USA. Med Univ S Carolina, Coll Dent Med, Charleston, SC 29403 USA. Med Univ S Carolina, Dept Biostat Bioinformat & Epidemiol, Charleston, SC 29403 USA. RP Huang, Y (reprint author), Med Univ S Carolina, Ralph H Johnson Vet Affairs Med Ctr, 114 Doughty St, Charleston, SC 29403 USA. EM huangyan@musc.edu NR 41 TC 37 Z9 38 U1 1 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 E534 EP E542 DI 10.1152/ajpendo.00462.2004 PG 9 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 962MV UT WOS:000231737800003 PM 15941782 ER PT J AU Akiba, Y Jung, M Ouk, S Kaunitz, JD AF Akiba, Y Jung, M Ouk, S Kaunitz, JD TI A novel small molecule CFTR inhibitor attenuates HCO3- secretion and duodenal ulcer formation in rats SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE CFTRinh-172; duodenal bicarbonate secretion; duodenal ulcer; cysteamine; luminal acid ID MUCOSAL ALKALINE SECRETION; CYSTIC-FIBROSIS; BICARBONATE SECRETION; INTRACELLULAR PH; FLUID SECRETION; ACID-SECRETION; LUMINAL ACID; CYSTEAMINE; MECHANISMS; PROTECTION AB The cystic fibrosis (CF) transmembrane conductance regulator ( CFTR) plays a crucial role in mediating duodenal bicarbonate (HCO3-) secretion (DBS). Although impaired DBS is observed in CF mutant mice and in CF patients, which would predict increased ulcer susceptibility, duodenal injury is rarely observed in CF patients and is reduced in CF mutant mice. To explain this apparent paradox, we hypothesized that CFTR dysfunction increases cellular [HCO3-] and buffering power. To further test this hypothesis, we examined the effect of a novel, potent, and highly selective CFTR inhibitor, CFTRinh-172, on DBS and duodenal ulceration in rats. DBS was measured in situ using a standard loop perfusion model with a pH stat under isoflurane anesthesia. Duodenal ulcers were induced in rats by cysteamine with or without CFTRinh-172 pretreatment 1 h before cysteamine. Superfusion of CFTRinh-172 (0.1 - 10 mu M) over the duodenal mucosa had no effect on basal DBS but at 10 mu M inhibited acid-induced DBS, suggesting that its effect was limited to CFTR activation. Acid-induced DBS was abolished at 1 and 3 h and was reduced 24 h after treatment with CFTRinh-172, although basal DBS was increased at 24 h. CFTRinh-172 treatment had no effect on gastric acid or HCO3- secretion. Duodenal ulcers were observed 24 h after cysteamine treatment but were reduced in CFTRinh-172-pretreated rats. CFTRinh-172 acutely produces CFTR dysfunction in rodents for up to 24 h. CFTR inhibition reduces acid-induced DBS but also prevents duodenal ulcer formation, supporting our hypothesis that intracellular HCO3- may be an important protective mechanism for duodenal epithelial cells. C1 Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Chem, Los Angeles, CA 90024 USA. Ctr Ulcer Res & Educ, Digest Dis Res Ctr, Los Angeles, CA USA. Brentwood Biomed Res Inst, Los Angeles, CA USA. RP Kaunitz, JD (reprint author), W Los Angeles VA Med Ctr, Bldg 114,Suite 217,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM jake@ucla.edu FU NIDDK NIH HHS [R01-DK-54221, P30-DK-0413] NR 52 TC 26 Z9 28 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD OCT PY 2005 VL 289 IS 4 BP G753 EP G759 DI 10.1152/ajpgi.00130.2005 PG 7 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 963VF UT WOS:000231833500017 PM 15905414 ER PT J AU Woods, LL Ingelfinger, JR Rasch, R AF Woods, LL Ingelfinger, JR Rasch, R TI Modest maternal protein restriction fails to program adult hypertension in female rats SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE perinatal programming; nephron number; gene expression; gender; renin-angiotensin system ID RENIN-ANGIOTENSIN SYSTEM; AMBULATORY BLOOD-PRESSURE; CORONARY-HEART-DISEASE; CARDIOVASCULAR-DISEASE; BIRTH-WEIGHT; NEONATAL UNINEPHRECTOMY; GENDER-DIFFERENCES; FETAL EXPOSURE; RENAL-FUNCTION; WOMEN AB Modest maternal dietary protein restriction in the rat leads to hypertension in adult male offspring. The purpose of this study was to determine whether female rats are resistant to developing the increased blood pressure seen in male rats after maternal protein restriction. Pregnant rats were fed a normal protein (19%, NP) or low-protein (8.5%, LP) diet throughout gestation. Renal renin protein and ANG II levels were reduced by 50-65% in male LP compared with NP pups, but were not suppressed in female LP compared with female NP. Mean arterial pressure in conscious, chronically instrumented adult female offspring (22 wk) was not different in LP (LP: 120 +/- 3 mmHg vs. NP: 121 +/- 2 mmHg), and glomerular filtration rate was also not different in LP vs. NP. The number of glomeruli per kidney was similar in adult LP and NP female offspring (LP: 26,050 +/- 2,071 vs. NP: 26,248 +/- 1,292, NP), and individual glomerular volume was also not different (LP: 0.92 +/- 0.11 10(6) mu m(3), LP vs. NP: 1.07 +/- 0.11 10(6) mu m(3)); the total volume of all glomeruli per kidney was also not significantly different. Thus female rats are relatively resistant to the programming for adult hypertension by perinatal protein restriction that we have described in males. This resistance may be due to the fact that modest maternal protein restriction does not reduce the number of glomeruli with which females are endowed as it does in males. The intrarenal renin-angiotensin system during development may play a key role in this protective effect of female gender. C1 Oregon Hlth & Sci Univ, Div Nephrol & Hypertens, Portland, OR 97239 USA. Massachusetts Gen Hosp, Pediat Nephrol Unit, Boston, MA 02114 USA. Univ Aarhus, Inst Anat, Dept Cell Biol, Aarhus, Denmark. RP Oregon Hlth & Sci Univ, Div Nephrol & Hypertens, L463,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM woodsl@ohsu.edu FU NHLBI NIH HHS [HL-48455, HL-70132]; NICHD NIH HHS [P-01-HD-34430, R01-HD-41074]; NIDDK NIH HHS [DK-58950] NR 42 TC 119 Z9 120 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 EI 1522-1490 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD OCT PY 2005 VL 289 IS 4 BP R1131 EP R1136 DI 10.1152/ajpregu.00037.2003 PG 6 WC Physiology SC Physiology GA 966RC UT WOS:000232037600027 PM 15961538 ER PT J AU Shmukler, BE Kurschat, CE Ackermann, GE Jiang, LW Zhou, Y Barut, B Stuart-Tilley, AK Zhao, JH Zon, LI Drummond, IA Vandorpe, DH Paw, BH Alper, SL AF Shmukler, BE Kurschat, CE Ackermann, GE Jiang, LW Zhou, Y Barut, B Stuart-Tilley, AK Zhao, JH Zon, LI Drummond, IA Vandorpe, DH Paw, BH Alper, SL TI Zebrafish slc4a2/ae2 anion exchanger: cDNA cloning, mapping, functional characterization, and localization SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE AE2; chloride/bicarbonate exchanger ID RENAL TUBULAR-ACIDOSIS; AE2 CL-/HCO3-EXCHANGER; RADIATION HYBRID MAP; DANIO-RERIO; PHOSPHATE COTRANSPORTER; MOLECULAR-CLONING; INTRACELLULAR PH; CELL-LINE; TRANSPORT; KIDNEY AB Although the zebrafish has been used increasingly for the study of pronephric kidney development, studies of renal ion transporters and channels of the zebrafish remain few. We report the cDNA cloning and characterization of the AE2 anion exchanger ortholog from zebrafish kidney, slc4a2/ae2. The ae2 gene in linkage group 2 encodes a polypeptide of 1,228 aa exhibiting 64% aa identity with mouse AE2a. The exon-intron boundaries of the zebrafish ae2 gene are nearly identical to those of the rodent and human genes. Whole-mount in situ hybridization detects ae2 mRNA in prospective midbrain as early as the five-somite stage, then later in the pronephric primordia and the forming pronephric duct, where it persists through 72 h postfertilization (hpf). Zebrafish Ae2 expressed in Xenopus laevis oocytes mediates Na(+)-independent, electroneutral (36)Cl(-)/Cl(-) exchange moderately sensitive to inhibition by DIDS, is inhibited by acidic intracellular pH and by acidic extracellular pH, but activated by ( acidifying) ammonium and by hypertonicity. Zebrafish Ae2 also mediates Cl(-)/HCO(3)(-) exchange in X. laevis oocytes and accumulates in or near the plasma membrane in transfected HEK-293 cells. In 24 - 48 hpf zebrafish embryos, the predominant but not exclusive localization of Ae2 polypeptide is the apical membrane of pronephric duct epithelial cells. Thus Ae2 resembles its mammalian orthologs in function, mechanism, and acute regulation but differs in its preferentially apical expression in kidney. These results will inform tests of the role of Ae2 in zebrafish kidney development and function. C1 Beth Israel Deaconess Med Ctr, Renal Unit, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Mol & Vasc Med Unit, Boston, MA 02215 USA. Harvard Univ, Div Hematol, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Howard Hughes Med Inst, Sch Med, Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Renal Unit, Boston, MA 02115 USA. Harvard Univ, Dept Med, Sch Med, Boston, MA 02115 USA. Harvard Univ, Dept Pediat, Sch Med, Boston, MA 02115 USA. RP Alper, SL (reprint author), Beth Israel Deaconess Med Ctr, Mol Med Unit, E-RW763,330 Brookline Ave, Boston, MA 02215 USA. EM salper@bidmc.harvard.edu FU NHLBI NIH HHS [HL-32262]; NIDDK NIH HHS [DK-43495, DK-53093] NR 65 TC 26 Z9 26 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD OCT PY 2005 VL 289 IS 4 BP F835 EP F849 DI 10.1152/ajprenal.00122.2005 PG 15 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 963VD UT WOS:000231833300021 PM 15914778 ER PT J AU Perlis, RH Perlis, CS Wu, Y Hwang, C Joseph, M Nierenberg, AA AF Perlis, RH Perlis, CS Wu, Y Hwang, C Joseph, M Nierenberg, AA TI Industry sponsorship and financial conflict of interest in the reporting of clinical trials in psychiatry SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID BIOMEDICAL-RESEARCH; COMPETING INTERESTS; PSYCHOPHARMACOLOGY; ASSOCIATION; DISCLOSURE; QUALITY; SCIENCE AB Objective: Financial conflict of interest has been reported to be prevalent in clinical trials in general medicine and associated with a greater likelihood of reporting results favorable to the intervention being studied. The extent and implications of industry sponsorship and financial conflict of interest in psychiatric clinical trials have not been investigated, to the authors' knowledge. Method: The authors examined funding source and author financial conflict of interest in all clinical trials published in the American Journal of Psychiatry, the Archives of General Psychiatry, the Journal of Clinical Psychopharmacology, and the Journal of Clinical Psychiatry between 2001 and 2003. Results: Among 397 clinical trials identified, 239 (60%) reported receiving funding from a pharmaceutical company or other interested party, and 187 studies (47%) included at least one author with a reported financial conflict of interest. Among the 162 randomized, double-blind, placebo-controlled studies examined, those that reported conflict of interest were 4.9 times more likely to report positive results; this association was significant only among the subset of pharmaceutical industry-funded studies. Conclusions: Author conflict of interest appears to be prevalent among psychiatric clinical trials and to be associated with a greater likelihood of reporting a drug to be superior to placebo. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Brown Univ, Dept Dermatol, Providence, RI 02912 USA. RP Perlis, RH (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. EM rperlis@partners.org NR 24 TC 167 Z9 171 U1 0 U2 7 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD OCT PY 2005 VL 162 IS 10 BP 1957 EP 1960 DI 10.1176/appi.ajp.162.10.1957 PG 4 WC Psychiatry SC Psychiatry GA 969YJ UT WOS:000232271600022 PM 16199844 ER PT J AU Kelleher, CM Silverman, EK Broekelmann, T Litonjua, AA Hernandez, M Sylvia, JS Stoler, J Reilly, JJ Chapman, HA Speizer, FE Weiss, ST Mecham, RP Raby, BA AF Kelleher, CM Silverman, EK Broekelmann, T Litonjua, AA Hernandez, M Sylvia, JS Stoler, J Reilly, JJ Chapman, HA Speizer, FE Weiss, ST Mecham, RP Raby, BA TI A functional mutation in the terminal exon of elastin in severe, early-onset chronic obstructive pulmonary disease SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article DE chronic obstructive pulmonary disease; elastin; extracellular matrix; genetics; mutation ID AIR-FLOW OBSTRUCTION; GENOME-WIDE LINKAGE; CUTIS-LAXA; ABNORMAL TROPOELASTIN; CHRONIC-BRONCHITIS; MORBID-OBESITY; EMPHYSEMA; GENE; INDUCTION; DOMINANT AB We describe a novel variant in the terminal exon of human elastin, c.2318 G > A, resulting in an amino acid substitution of glycine 773 to aspartate (G773D) in a pedigree with severe early-onset chronic obstructive pulmonary disease (COPD). Transfection studies with elastin cDNAs demonstrate that the glycine to aspartate change compromises the ability of the mutant protein to undergo normal elastin assembly. Other functional consequences of this amino acid substitution include altered proteolytic susceptibility of the C-terminal region of elastin and reduced interaction of the exon 36 sequence with matrix receptors on cells. These results suggest that the G773D variant confers structural and functional consequences relevant to the pathogenesis of COPD. C1 Washington Univ, Sch Med, Dept Cell Biol & Physiol, St Louis, MO 63110 USA. Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Pulm & Crit Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02138 USA. Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Div Pulm & Crit Care Med, Boston, MA USA. Univ Calif San Francisco, Dept Med, Div Pulm & Crit Med, San Francisco, CA 94143 USA. RP Silverman, EK (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA. EM ed.silverman@channing.harvard.edu FU NHLBI NIH HHS [HL67204, N01HR761015, N01HR761018, HL075478, N01HR761012, N01HR76103, N01HR76106, N01HR76109, N01HR76107, HL71960, HL71393, HL74138, N01HR761010, N01HR76104, N01HR761019, N01HR761016, N01HR76101, T32 HL07873, N01HR761013, HL074193, HL53325, HL61575, N01HR761011, N01HR761014, N01HR761017, N01HR76102, N01HR76105, N01HR76108] NR 45 TC 39 Z9 40 U1 0 U2 2 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD OCT PY 2005 VL 33 IS 4 BP 355 EP 362 DI 10.1165/rcmb.2005-02060C PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 972HN UT WOS:000232445000006 PM 16081882 ER PT J AU Kuang, PP Lucey, E Rishikof, DC Humphries, DE Bronsnick, D Goldstein, RH AF Kuang, PP Lucey, E Rishikof, DC Humphries, DE Bronsnick, D Goldstein, RH TI Engraftment of neonatal lung fibroblasts into the normal and elastase-injured lung SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article DE elastase; elastin; emphysema; fibroblasts ID ALVEOLAR FIBROBLASTS; RAT LUNG; INDUCED EMPHYSEMA; POSTNATAL-GROWTH; GENE-EXPRESSION; CELL-FUSION; ALPHA; DISEASES; PROLIFERATION; LYMPHOCYTES AB Interstitial fibroblasts are an integral component of the alveolar wall. These cells produce matrix proteins that maintain the extracellular scaffold of alveolar structures. Emphysema is characterized by airspace enlargement resulting from the loss of alveolar cellularity and matrix. In this study, we explored the endotracheal delivery of fibroblasts to the lung parenchyma as a means of repairing damaged alveolar structures directly or indirectly for the delivery of transgenes. Fibroblasts were isolated from the lungs of neonatal transgenic mice expressing GFP during the period of rapid alveolarization. These GFP(+) cells maintained their myofibroblast phenotype in culture and expressed elastin and a-smooth muscle actin mRNA. We administered GFP(+) fibroblasts to saline- and elastase-treated mice by endotracheal instillation. We detected more GFP(+) fibroblasts in the alveolar walls and in the interstitial areas of elastase-injured lungs than in normal lungs as assessed by immunohistochemistry and fluorescent imaging. The presence of GFP(+) fibroblasts in the interstitium demonstrated transepithelial migration of these cells. Expression of GFP(+) fibroblasts in recipient lungs was maintained for at least 20 d after endotracheal administration. These cells synthesize matrix components including elastin in vitro and could contribute to restoring the structural integrity of the alveolar wall. C1 Boston Univ, Sch Med, Ctr Pulm, Boston, MA 02118 USA. VA Boston Healthcare Syst, Boston, MA USA. RP Goldstein, RH (reprint author), Boston Univ, Sch Med, Ctr Pulm, 715 Albany St,R-304, Boston, MA 02118 USA. EM rgoldstein@lung.bumc.bu.edu FU NHLBI NIH HHS [HL46902, HL66547] NR 32 TC 10 Z9 13 U1 0 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD OCT PY 2005 VL 33 IS 4 BP 371 EP 377 DI 10.1165/rcmb.2004-0319OC PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 972HN UT WOS:000232445000008 PM 16037486 ER PT J AU DeMeo, DL Reilly, JJ Ginns, LC Sylvia, JS Silverman, EK AF DeMeo, DL Reilly, JJ Ginns, LC Sylvia, JS Silverman, EK TI Concordance of genotypes in pre- and post-lung transplantation DNA samples SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article DE genetic epidemiology; lung; chimerism; transplantation ID POLYMERASE CHAIN-REACTION; BLOOD ALLOGENEIC MICROCHIMERISM; ALLOGRAFT RECIPIENTS; MIXED CHIMERISM; AMPLIFICATION AB Genetic epidemiology studies of end-stage lung disease are potentially hindered by low numbers of participants due to early death of patients from the underlying disease, or due to exclusion from studies after patients have had lung transplants, because of concern about bias of genotype data due to chimerism. The number of participants enrolled in genetic studies of end-stage lung disease could be increased by including those individuals who have undergone lung transplant. We hypothesized that individuals who have had lung transplants can be included in genetic epidemiology studies that use single nucleotide polymorphism and short tandem repeat marker data, without confounding due to chimerism. Ten probands with severe, early-onset chronic obstructive pulmonary disease were included in this analysis. Pre- and post-lung transplant DNA samples were used in the investigation of concordance of genotype results for 12 short tandem repeat markers and 23 single nucleotide polymorphisms. Concordance was observed for all genotypes before and after lung transplant. We conclude that the risk of biasing genetic epidemiology studies due to donor lung-related DNA microchimerism is low, and that the inclusion of post-lung transplantation participants will allow for larger genetic epidemiology studies of individuals with end-stage lung disease. C1 Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Div Pulm & Crit Care Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Pulm & Crit Care Med, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP DeMeo, DL (reprint author), Brigham & Womens Hosp, Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA. EM redld@channing.harvard.edu FU NHLBI NIH HHS [K08 HL72918, HL71393, HL075478, HL61575] NR 14 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD OCT PY 2005 VL 33 IS 4 BP 402 EP 405 DI 10.1165/rcmb.2005-01420C PG 4 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 972HN UT WOS:000232445000012 PM 15994430 ER PT J AU Maher, MM Kalra, MK Titton, RL Boland, GW Wittram, C Aquino, S Mueller, PR Shepard, JAO AF Maher, MM Kalra, MK Titton, RL Boland, GW Wittram, C Aquino, S Mueller, PR Shepard, JAO TI Percutaneous lung biopsy in a patient with a cavitating lung mass: Indications, technique, and complications SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Editorial Material ID TRANSTHORACIC NEEDLE-BIOPSY; PULMONARY NODULES; ASPIRATION; LESIONS; PNEUMOTHORAX; ANGLE; CHEST C1 Massachusetts Gen Hosp, Div Thorac Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Abdominal Imaging & Intervent Radiol, Boston, MA 02114 USA. RP Maher, MM (reprint author), Massachusetts Gen Hosp, Div Thorac Radiol, 55 Fruit St, Boston, MA 02114 USA. EM mmaher@partners.org NR 15 TC 5 Z9 5 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD OCT PY 2005 VL 185 IS 4 BP 989 EP 994 DI 10.2214/AJR.05.0489 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 968EZ UT WOS:000232146000028 PM 16177421 ER PT J AU Abbara, S Cury, RC Nieman, K Reddy, V Moselewski, F Schmidt, S Ferencik, M Hoffmann, U Brady, TJ Achenbach, S AF Abbara, S Cury, RC Nieman, K Reddy, V Moselewski, F Schmidt, S Ferencik, M Hoffmann, U Brady, TJ Achenbach, S TI Noninvasive evaluation of cardiac veins with 16-MDCT angiography SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID ADVANCED HEART-FAILURE; CORONARY-SINUS; ANATOMY; TACHYCARDIA; TRIBUTARIES; CT AB OBJECTIVE. Anatomic mapping of the cardiac veins is important to guide transvenous therapeutic procedures such as biventricular pacing. As an alternative to invasive venography, we studied the feasibility of MDCT of the cardiac venous anatomy. CONCLUSION. Cardiac venous anatomy is variable. MDCT is a noninvasive method that allows detailed imaging of the cardiac venous anatomy, including small cardiac veins and thebesian valves. Therefore, cardiac MDCT may be a valuable tool for guiding procedures that involve the cardiac venous system. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, CIMIT, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA. RP Abbara, S (reprint author), Massachusetts Gen Hosp, Dept Radiol, 100 Charles River Plaza,Ste 400, Boston, MA 02114 USA. NR 16 TC 42 Z9 48 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD OCT PY 2005 VL 185 IS 4 BP 1001 EP 1006 DI 10.2214/AJR.04.1382 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 968EZ UT WOS:000232146000030 PM 16177423 ER PT J AU Jones, JL Zabicki, K Christian, RL Gadd, MA Hughes, KS Lesnikoski, BA Rhei, E Specht, MC Dominguez, FJ Smith, BL AF Jones, JL Zabicki, K Christian, RL Gadd, MA Hughes, KS Lesnikoski, BA Rhei, E Specht, MC Dominguez, FJ Smith, BL TI A comparison of sentinel node biopsy before and after neoadjuvant chemotherapy: timing is important SO AMERICAN JOURNAL OF SURGERY LA English DT Article; Proceedings Paper CT 6th Annual Meeting of the American-Society-of-Breast-Surgeons CY MAR 16-20, 2005 CL Los Angeles, CA SP Amer Soc Breast Surgeons DE breast cancers; sentinel lymph node biopsy; neoadjuvant chemotherapy ID SURGICAL ADJUVANT BREAST; INDUCTION CHEMOTHERAPY; CANCER; CARCINOMA; SURGERY; FEASIBILITY AB Background Because neoadjuvant chemotherapy is being used more frequently, the optimal timing of sentinel node biopsy (SNB) remains controversial. We previously evaluated the predictive value of SNB before neoadjuvant chemotherapy in clinically node-negative breast cancer. Our identification rate of the sentinel node among 52 patients before chemotherapy with a mean tumor size of 4 cm was 100%. In this study, we compared the identification rates of SNB before and after neoadjuvant chemotherapy and evaluated the false-negative rate of SNB after chemotherapy. Methods: A retrospective institutional database review identified 36 women who underwent SNB after neoadjuvant chemotherapy for breast cancer from 1999 to 2004. The initial clinical tumor size and lymph node status, SNB pathology, axillary lymph node dissection pathology, and residual pathologic tumor size were reviewed. Results: Sixteen of 36 patients had a clinically negative axilla before neoadjuvant therapy. SNB after neoadjuvant therapy was successful in 29 patients (80.6%), although 7 patients did not map (19.4%). Six of the 7 patients who failed to map had a clinically positive axilla initially. Axillary disease was found in 6 of 7 of these patients at dissection (85.7%). Of the 29 patients who mapped successfully, 13 (45%) were SNB negative, and 16 (55%) were SNB positive. Of the 13 SNB-negative patients, 2 had a positive axillary lymph node dissection, yielding a false-negative rate of 11%. Thirteen patients who mapped had a clinically positive axilla before therapy (45%). Of the 11 patients with true-negative SNBs, 7 (64%) were clinically node negative at presentation. The initial tumor sizes on examination ranged from 2 to 9 cm (mean, 5.0 cm), and residual pathologic tumor sizes ranged from 0 to 6 cm (mean, 1.8 cm). Failure to map correlated with a clinically positive axilla at presentation (100% vs 45%) but did not correlate with initial tumor size. Conclusions: Sentinel node identification rates are significantly better when mapping is performed before neoadjuvant chemotherapy (100% vs 80.6%), with failure to map correlated with clinically positive nodal disease at presentation and residual disease at axillary lymph node dissection. Among patients who map successfully after chemotherapy, the false-negative rate is high (11%). Given these findings, we currently recommend SNB before neoadjuvant chemotherapy for clinically node-negative patients, and raise concerns about the use of SNB after neoadjuvant therapy in patients with an initially clinically positive axilla. (c) 2005 Excerpta Medica Inc. All rights reserved. C1 Massachusetts Gen Hosp, Dept Surg Oncol, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Surg Oncol, Boston, MA 02115 USA. RP Jones, JL (reprint author), Massachusetts Gen Hosp, Dept Surg Oncol, 55 Fruit St,Yawkey Bldg,7th Floor, Boston, MA 02114 USA. EM jjones17@partners.org OI Hughes, Kevin/0000-0003-4084-6484 NR 12 TC 57 Z9 61 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD OCT PY 2005 VL 190 IS 4 BP 517 EP 520 DI 10.1016/j.amjsurg.2005.06.004 PG 4 WC Surgery SC Surgery GA 968VA UT WOS:000232189600002 PM 16164912 ER PT J AU Brachtel, EF Sanchez-Estevez, C Moreno-Bueno, G Prat, J Palacios, J Oliva, E AF Brachtel, EF Sanchez-Estevez, C Moreno-Bueno, G Prat, J Palacios, J Oliva, E TI Distinct molecular alterations in complex endometrial hyperplasia (CEH) with and without immature squamous metaplasia (squamous morules) SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE endometrial hyperplasia; immature squamous metaplasia (squamous morules); beta-catenin; PTEN; K-ras; microsatellite instability ID BETA-CATENIN MUTATIONS; MICROSATELLITE INSTABILITY; GAMMA-CATENIN; CLINICOPATHOLOGICAL FEATURES; ATYPICAL HYPERPLASIA; OVARIAN CARCINOMAS; TUMOR-SUPPRESSOR; EXPRESSION; GENE; DIFFERENTIATION AB Several molecular alterations, most commonly PTEN mutations but also K-ras mutations, microsatellite instability, and beta-catenin mutations have been detected in endometrioid endometrial carcinoma (EEC). Specifically, mutations in the beta-catenin gene are seen in 15% to 20% of EECs, whereas immunohistochemical expression of beta-catenin ranges from 13% to 44%, nuclear staining being concentrated in areas of immature squamous metaplasia (squamous morules). Complex endometrial hyperplasia with atypia (CEH-A) is a well-known precursor of EEC, which can also show immature squamous metaplasia. In this study, we compared the immunohistochemical and molecular profiles of 13 CEH-A with and 11 CEH-A without squamous morules (SM) for mutations of beta-catenin, PTEN K-ras, and microsatellite instability (MSI). In all cases of CEH-A with SM, beta-catenin immunostaining showed strong and diffuse nuclear expression in areas of SM and weak to moderate nuclear expression in the glandular component. Six different beta-catenin mutations were found in 7 of 13 cases (54%) (G34E, G34V, S33C, D32Y, S33F, D32A); however, no mutations of the PTEN or K-ras genes were identified. beta-Catenin immunostaining showed focal nuclear staining in only 2 cases of CEH-A without SM. Only 1 case had a beta-catenin mutation (S45A), which was associated with a K-ras mutation (G12D). Another 3 cases had both PTEN and K-ras mutations (C296Stop Ex 8 and G12V, 244del C Ex 7 and G12D, 251 ins TGAT Ex 7 and G13D), and one had a PTEN mutation (G230E Ex 7) only. Of all 24 cases, only 1 case of CEH-A without SM showed MSI. In conclusion, marked differences in the molecular profiles regarding beta-catenin, PTEN, and K-ras mutations were observed between CEH-A with and without SM. beta-catenin mutations might represent a signaling pathway leading to a distinctive morphology in hyperplastic/neoplastic endometrium with SM. Other molecular events such as K-ras or PTEN mutations are likely to occur in CEH-A independently from beta-catenin. Furthermore, morphologic differences between CEH-A with SM and CEH-A without SM seem to correlate, at least to some extent, with the clinical course of the disease. In our series, cases of CEH-A with SM and beta-catenin alterations appeared to have a less aggressive behavior when compared with CEH-A without SM and with K-ras and PTEN mutations. C1 Harvard Univ, Dept Pathol, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Ctr Nacl Invest Oncol, Lab Breast & Gynecol Canc, Madrid, Spain. Hosp Santa Cruz & San Pablo, Dept Pathol, E-08025 Barcelona, Spain. RP Brachtel, EF (reprint author), Harvard Univ, Dept Pathol, Massachusetts Gen Hosp, Sch Med, 55 Fruit St,WRN 2, Boston, MA 02114 USA. EM ebrachtel@partners.org RI Prat, Jaime/G-4679-2011; Moreno-Bueno, Gema/K-9354-2016 OI Moreno-Bueno, Gema/0000-0002-5030-6687 NR 36 TC 37 Z9 39 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD OCT PY 2005 VL 29 IS 10 BP 1322 EP 1329 DI 10.1097/01.pas.0000171001.87599.e2 PG 8 WC Pathology; Surgery SC Pathology; Surgery GA 967WB UT WOS:000232120800009 PM 16160475 ER PT J AU Zembowicz, A Garcia, CF Tannous, ZS Mihm, MC Koerner, F Pilch, BZ AF Zembowicz, A Garcia, CF Tannous, ZS Mihm, MC Koerner, F Pilch, BZ TI Endocrine mucin-producing sweat gland carcinoma - Twelve new cases suggest that it is a precursor of some invasive mucinous carcinomas SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article; Proceedings Paper CT 94th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY FEB 26-MAR 04, 2005 CL San Antonio, TX SP US Canadian Acad Pathol DE endocrine mucin-producing sweat gland carcinoma; endocrine ductal carcinoma in situ; solid papillary carcinoma; mucinous carcinoma; eccrine carcinoma; neuroendocrine carcinoma ID SOLID PAPILLARY CARCINOMA; MYOEPITHELIAL CELLS; ECCRINE CARCINOMA; BREAST; SKIN; DIFFERENTIATION; ADENOCARCINOMA; FORM AB Endocrine mucin-producing sweat gland carcinoma (EMPSGC) is an underrecognized low-grade carcinoma with predilection to the eyelid. Only 4 cases of this entity have been described in the literature. Here, we describe 12 cases of EMPSGC. The lesions were twice as frequent in females than males with an average age of 70 years (range, 48-84 years). Clinically, they presented as a slowly growing cyst or swelling. The most common site of occurrence was the lower eyelid (8 cases). Two lesions occurred on the upper eyelid and 2 on the cheek. Histologically, they were well-circumscribed, typically multinodular tumors with solid or partially cystic nodules, frequently showing areas of papillary architecture. Focal cribriform arrangements were also present. The nodules were formed by uniform small- to medium-sized oval to polygonal epithelial cells with lightly eosinophilic to bluish cytoplasm. The nuclei were bland with diffusely stippled chromatin and inconspicuous nucleoli. Intracytoplasmic and extracellular mucin was usually present. Mitotic activity was present but never brisk. All tumors examined immunohistochemically expressed at least one neuroendocrine marker, synaptophysin or chromogranin. CD57 and neuron specific enolase, secondary markers of neuroendocrine differentiation, were expressed in most cases. All tumors tested expressed estrogen and progesterone receptors, cytokeratin 7, low molecular cytokeratin Cam5.2, and epithelial membrane antigen and were negative for cytokeratin 20 and S-100 protein. Calponin, smooth muscle actin, and p63 immunohistochemical stains did not disclose myoepithelial cells around larger tumor nests in most cases, supporting the notion that EMPSGC is an invasive carcinoma. In 10 cases, cystic areas lined by benign epithelium indistinguishable from eccrine ducts were present. In some foci, the benign ductal epithelium was undermined or replaced by carcinoma in situ with similar cytologic features to the solid or papillary areas of EMPSGC. Myoepithelial cells were preserved in the areas of in situ carcinoma. In 6 cases, EMPSGC was associated with invasive mucinous carcinoma. In situ carcinoma and mucinous carcinoma also expressed neuroendocrine markers. Clinical follow-up showed no recurrences or metastases, consistent with low-grade carcinoma. The series provides histologic evidence for a multistage progression of noninvasive sweat gland neuroendocrine carcinoma to EMPSGC and then to mucinous carcinoma of the eyelid. Although the data from this series support the notion that the prognosis of EMPSGC and mucinous carcinoma is good, longer follow-up is needed for better understanding of their pathogenesis and clinical behavior. C1 Massachusetts Gen Hosp, Dermatopathol Unit, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Dermatol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Zembowicz, A (reprint author), Massachusetts Gen Hosp, Dermatopathol Unit, Dept Pathol, Warren 820,55 Fruit St, Boston, MA 02114 USA. EM azembowicz@partners.org NR 19 TC 29 Z9 29 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD OCT PY 2005 VL 29 IS 10 BP 1330 EP 1339 DI 10.1097/01.pas.0000170348.40057.60 PG 10 WC Pathology; Surgery SC Pathology; Surgery GA 967WB UT WOS:000232120800010 PM 16160476 ER PT J AU Baker, PM Moch, H Oliva, E AF Baker, PM Moch, H Oliva, E TI Unusual morphologic features of endometrial stromal tumors - A report of 2 cases SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE endometrial stromal neoplasia; unusual morphologic features; bizarre nuclei; fatty metaplasia; skeletal muscle differentiation ID SMOOTH-MUSCLE TUMORS; UNUSUAL HISTOLOGIC FEATURES; CORD-LIKE AREAS; CLINICOPATHOLOGICAL ANALYSIS; GLANDULAR DIFFERENTIATION; FOLLOW-UP; UTERUS; SARCOMA; UTERINE; STROMOMYOMA AB Endometrial stromal tumors with typical morphology usually do not pose diagnostic problems. However, the finding of unusual morphologic features may be misleading in the final interpretation of these tumors. Herein, we described two endometrial stromal sarcomas discovered in hysterectomy specimens of women 31 and 75 years of age. Features typical of endometrial stromal neoplasia were present in both cases. Additionally, in I case, extensive fatty metaplasia as well as smooth and skeletal muscle metaplasia were found; and in the second case, focal bizarre nuclei, smooth muscle differentiation, and fibrous change were present. The differential diagnosis in the first case included cellular intravenous leiomyomatosis/lipoleiomyomatosis with skeletal muscle differentiation; and in the second case, a cellular smooth muscle tumor with bizarre nuclei was considered. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Univ Zurich Hosp, Dept Pathol, Inst Surg Pathol, CH-8091 Zurich, Switzerland. Hlth Sci Ctr, Dept Pathol, Winnipeg, MB, Canada. RP Oliva, E (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St, Boston, MA 02114 USA. EM eoliva@partners.org NR 30 TC 24 Z9 25 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD OCT PY 2005 VL 29 IS 10 BP 1394 EP 1398 DI 10.1097/01.pas.0000172295.05527.28 PG 5 WC Pathology; Surgery SC Pathology; Surgery GA 967WB UT WOS:000232120800018 PM 16160484 ER PT J AU Narita, M Fujitani, S Haake, DA Paterson, DL AF Narita, M Fujitani, S Haake, DA Paterson, DL TI Leptospirosis after recreational exposure to water in the Yaeyama Islands, Japan SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID UNITED-STATES; CLIMATE VARIABILITY; OUTBREAK; LIPOPOLYSACCHARIDE; CHEMOPROPHYLAXIS; INFECTIONS; CARRIAGE; EPIDEMIC; BARBADOS; IMPACTS AB Leptospirosis is a global zoonotic disease with a variety of clinical manifestations. We report an outbreak of leptospirosis in the Yaeyama Islands, Japan, in the summer of 1999 associated with heavy rainfall. Fourteen people were diagnosed with leptospirosis and required hospitalization. All cases were found to have exposure to contaminated soil or water. A history of recreational activities involving water sports was more frequent (71%) than occupational risk factors related to agriculture or construction (29%). Fever was the primary symptom in all cases, followed by chills (93%), headache (86%), myalgias (57%) and conjunctival suffusion (57%). All cases were successfully treated with antimicrobial therapy except one patient who improved spontaneously. Jarisch-Herxheimer reactions were seen in six cases (43%). The increasing incidence of leptospirosis related to recreational sports is an important public health problem in resort areas. A high-index of suspicion, early treatment, and prevention are crucial in this latently endemic area. C1 Univ Pittsburgh, Dept Internal Med, Presbyterian Shadyside Internal Med Residency Pro, Pittsburgh, PA 15232 USA. Univ Pittsburgh, Med Ctr, Presbyterian Shadyside, Pittsburgh, PA 15232 USA. Univ Pittsburgh, Dept Crit Care Med, Pittsburgh, PA USA. VA Greater Los Angeles Healthcare Syst, Infect Dis Sect, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. Univ Pittsburgh, Div Infect Dis, Pittsburgh, PA USA. RP Narita, M (reprint author), Univ Pittsburgh, Dept Internal Med, Presbyterian Shadyside Internal Med Residency Pro, 5230 Ctr Ave, Pittsburgh, PA 15232 USA. EM naritam@upmc.edu RI Paterson, David/A-9258-2010 FU NIAID NIH HHS [R01 AI034431-08, R01 AI034431] NR 37 TC 39 Z9 40 U1 0 U2 2 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD OCT PY 2005 VL 73 IS 4 BP 652 EP 656 PG 5 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 973UR UT WOS:000232548600002 PM 16222003 ER PT J AU Lin, P Campbell, DG Chaney, EE Liu, CF Heagerty, P Felker, BL Hedrick, SC AF Lin, P Campbell, DG Chaney, EE Liu, CF Heagerty, P Felker, BL Hedrick, SC TI The influence of patient preference on depression treatment in primary care SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; COLLABORATIVE CARE; MAJOR DEPRESSION; VETERANS; MANAGEMENT; HEALTH; GUIDELINES; SCORE AB Background: The chronic illness model encourages consideration of patients' treatment preferences. Moreover, research suggests that matching treatment to preference might affect outcomes for patients with depression. Purpose: This investigation explored factors associated with treatment preference matching and the effects of matching on depression treatment outcomes. Methods: Treatment preferences were assessed among primary care patients with depression participating in a large randomized trial of depression management. Patients were offered antidepressant medication and/or counseling based on preference and several other factors. Depression was assessed at 3 and 9 months. Results: Participants who preferred medication were older were in worse physical health, and were more likely to already be taking antidepressants. Participants who preferred both medication and counseling evidenced greater agreement with the statement that depression is a medical illness. Overall, 72% of participants were matched with their preferred treatment; matched participants demonstrated more rapid improvement in depression symptomatology than unmatched participants. Conclusions: Obtaining preferred treatment appears to contribute to improved treatment outcome. Continued attempts to assess for and accommodate treatment preferences might result in better response to depression treatment. C1 VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Ctr Excellence, Seattle, WA 98108 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. RP Hedrick, SC (reprint author), VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Ctr Excellence, HSR&D 152,1660 S Columbian Way, Seattle, WA 98108 USA. EM susan.hedrick@med.va.gov NR 31 TC 81 Z9 84 U1 3 U2 7 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 164 EP 173 DI 10.1207/s15324796abm3002_9 PG 10 WC Psychology, Multidisciplinary SC Psychology GA 972CM UT WOS:000232431600009 PM 16173913 ER PT J AU Doshi, A Boudreaux, ED Wang, N Pelletier, AJ Camargo, CA AF Doshi, A Boudreaux, ED Wang, N Pelletier, AJ Camargo, CA TI National study of US emergency department visits for attempted suicide and self-inflicted injury, 1997-2001 SO ANNALS OF EMERGENCY MEDICINE LA English DT Article ID RISK-FACTORS; HARM; ADOLESCENTS; PREVALENCE; ACCIDENT; CHILDREN AB Study objective: We describe the epidemiology of emergency department (ED) visits for attempted suicide and self-inflicted injury. Methods: Data were obtained from the National Hospital Ambulatory Medical Care Survey, a national probability sample of ED visits. All visits for attempted suicide or self-inflicted injury (E950 to E959) during 1997 to 2001 were included in these analyses. Results: During the 5-year period, there were approximately 412,000 annual ED visits for attempted suicide and self-inflicted injury, or 0.4% of all ED visits. The annual visit rate was 1.5 (1.3 to 1.7) visits per 1,000 US citizens. The mean patient age was 31 years, and visits were most common among patients aged 15 to 19 years, at a rate of 3.3 (95% confidence interval 2.1 to 4.4). ED visit rates were higher among female patients (1.7) than male patients (1.3) and among blacks (1.9) than whites (1.5). Visit rates did not differ by metropolitan status or US region. The most common method of injury was poisoning (68%), followed by cutting or piercing (20%). One third of visiting patients were admitted to the hospital, with 31% of admissions going to the ICU. A psychiatric disorder was coded for 55% of visits, with depressive disorder accounting for 34% and alcohol abuse for 16%. Conclusion: ED visits for attempted suicide and self-inflicted injury are relatively common, serious, and most frequent among adolescents and young adults. Self-poisoning is the most common method. The high prevalence of psychiatric and substance abuse disorders in this population suggests these issues should be considered during management and disposition. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Emergency Med, EMNet Coordinating Ctr, Boston, MA 02114 USA. Univ Michigan, Sch Med, Ann Arbor, MI USA. Cooper Hosp Univ Med Ctr, Dept Emergency Med, Camden, NJ USA. Cooper Hosp Univ Med Ctr, Dept Psychiat, Camden, NJ USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Camden, NJ 08103 USA. RP Camargo, CA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Emergency Med, EMNet Coordinating Ctr, 326 Cambridge St,Suite 410, Boston, MA 02114 USA. EM ccamargo@partners.org OI Boudreaux, Edwin/0000-0002-3223-6371 FU NIDA NIH HHS [DA-16698] NR 29 TC 108 Z9 110 U1 2 U2 7 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD OCT PY 2005 VL 46 IS 4 BP 369 EP 375 DI 10.1016/j.annemergmed.2005.04.018 PG 7 WC Emergency Medicine SC Emergency Medicine GA 972CC UT WOS:000232430500012 PM 16183394 ER PT J AU Arar, NH Hazuda, H Steinbach, R Arar, MY Abboud, HE AF Arar, NH Hazuda, H Steinbach, R Arar, MY Abboud, HE TI Ethical issues associated with conducting genetic family studies of complex disease SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE genetic family studies; ethical issues; Contextual Assessment Approach; subject-centered approach ID INFORMED-CONSENT; CANCER; PARTICIPATION; PRIVACY; SCIENCE; RACE AB PURPOSE: To examine subjects' recognition of the risks and ethical issues associated with enrollment in genetic family studies (GFS) and explore how this recognition affects their informed and voluntary participation. METHODS: A cross-sectional study design including both quantitative and qualitative data was employed. Structured interviews using the Contextual Assessment Approach Questionnaire (CAA-Q) were conducted with 246 Mexican American (MA) participants. To gain in-depth understanding of questionnaire responses, semi-structured interviews with 30 participants were conducted. All participants were interviewed before their enrollment in the Family Investigation of Nephropathy and Diabetes (FIND). RESULTS: Subjects' average age was 56 years; 62% were females. Seventy-eight percent of participants were not formally educated beyond high school and 72% reported an annual household income of <= $20,000. Eighty-five percent agreed to provide researchers with information on relatives' ages, gender, and education. Sixty-five percent of participants were willing to provide identifiable information such as names, addresses, and phone numbers of relatives. Sixty-three percent of participants indicated that there were direct benefits (i.e., supporting research) to disclosing relatives' information. Seventy-six percent stated that there were no risks associated with participation in GFS (e.g., discrimination or confidentiality of genetic information) compared with 10% who said that there were such risks. While discussing potential risks, subjects did not consider these to influence their decision to participate. CONCLUSIONS: Subjects enrolled in GFS did not recognize and tended to underestimate the social and cultural risks associated with their participation in GFS. If subjects do not fully comprehend the risks, this raises questions concerning their ability to provide informed consent and to voluntarily participate. We propose a subject-centered approach that views enrollment as an active process in which subjects and recruiters give and receive information on risks and ethical issues related to participation, which enhances protection of the rights and welfare of subjects participating in GFS. C1 Univ Texas, Ctr Hlth Sci, Dept Med Nephrol, Div Nephrol, San Antonio, TX 78229 USA. Audie L Murphy Mem Vet Adm Med Ctr, Div Nephrol, Dept Pediat, San Antonio, TX 78284 USA. RP Arar, NH (reprint author), Univ Texas, Ctr Hlth Sci, Dept Med Nephrol, Div Nephrol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM ararn@uthscsa.edu FU NHGRI NIH HHS [1 R03 HG 02 381]; NIDDK NIH HHS [5 U01 DK57295] NR 46 TC 16 Z9 16 U1 0 U2 4 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 712 EP 719 DI 10.1016/j.annepidem.2004.09.010 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 969NF UT WOS:000232240200007 PM 16157258 ER PT J AU Goldhirsch, A Glick, JH Gelber, RD Coates, AS Thurlimann, B Senn, H Albain, KS Bergh, J Castiglione-Gertsch, M Coates, AS Costa, A Cuzick, J Davidson, N Forbes, JF Gelber, RD Goss, P Harris, J Glick, JH Goldhirsch, A Howell, A Ingle, JN Jakesz, R Jassem, J Kaufmann, M Martin, M Mauriac, L Morrow, M Mouridsen, HT Namer, M Piccart-Gebhart, MJ Possinger, K Pritchard, K Rutgers, EJT Thurlimann, B Viale, G Wallgren, A Wood, WC AF Goldhirsch, A Glick, JH Gelber, RD Coates, AS Thurlimann, B Senn, H Albain, KS Bergh, J Castiglione-Gertsch, M Coates, AS Costa, A Cuzick, J Davidson, N Forbes, JF Gelber, RD Goss, P Harris, J Glick, JH Goldhirsch, A Howell, A Ingle, JN Jakesz, R Jassem, J Kaufmann, M Martin, M Mauriac, L Morrow, M Mouridsen, HT Namer, M Piccart-Gebhart, MJ Possinger, K Pritchard, K Rutgers, EJT Thurlimann, B Viale, G Wallgren, A Wood, WC TI Meeting highlights: International Expert Consensus on the Primary Therapy of Early Breast Cancer 2005 SO ANNALS OF ONCOLOGY LA English DT Review ID ADJUVANT ENDOCRINE THERAPY; LYMPH-NODE INVOLVEMENT; ISOLATED TUMOR-CELLS; CARCINOMA IN-SITU; PHASE-III TRIAL; RANDOMIZED-TRIAL; ESTROGEN-RECEPTOR; POSTMENOPAUSAL WOMEN; PREMENOPAUSAL WOMEN; RADIATION-THERAPY AB The ninth St Gallen (Switzerland) expert consensus meeting in January 2005 made a fundamental change in the algorithm for selection of adjuvant systemic therapy for early breast cancer. Rather than the earlier approach commencing with risk assessment, the Panel affirmed that the first consideration was endocrine responsiveness. Three categories were acknowledged: endocrine responsive, endocrine non-responsive and tumors of uncertain endocrine responsiveness. The three categories were further divided according to menopausal status. Only then did the Panel divide patients into low-, intermediate- and high-risk categories. It agreed that axillary lymph node involvement did not automatically define high risk. Intermediate risk included both node-negative disease (if some features of the primary tumor indicated elevated risk) and patients with one to three involved lymph nodes without additional high-risk features such as HER2/neu gene overexpression. The Panel recommended that patients be offered chemotherapy for endocrine non-responsive disease; endocrine therapy as the primary therapy for endocrine responsive disease, adding chemotherapy for some intermediate- and all high-risk groups in this category; and both chemotherapy and endocrine therapy for all patients in the uncertain endocrine response category except those in the low-risk group. C1 European Inst Oncol, Int Breast Canc Study Grp, I-20141 Milan, Italy. Oncol Inst So Switzerland, Int Breast Canc Study Grp, Bellinzona, Switzerland. Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Canc Council Australia, Sydney, NSW, Australia. Univ Sydney, Sydney, NSW 2006, Australia. Kantonsspital, Div Gynecol Oncol, St Gallen, Switzerland. Zentrum Tumor Diagnost & Pravent, St Gallen, Switzerland. RP Goldhirsch, A (reprint author), European Inst Oncol, Int Breast Canc Study Grp, Via Ripamonti 435, I-20141 Milan, Italy. EM aron.goldhirsch@ibcsg.org; aron.goldhirsch@ibcsg.org OI Howell, Anthony/0000-0002-6233-719X FU NCI NIH HHS [CA-75362] NR 153 TC 698 Z9 754 U1 0 U2 18 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 IS 10 BP 1569 EP 1583 DI 10.1093/annonc/mdi326 PG 15 WC Oncology SC Oncology GA 974NC UT WOS:000232597700003 PM 16148022 ER PT J AU Ota, F Connor, NP Konopacki, R AF Ota, F Connor, NP Konopacki, R TI Alterations in contractile properties of tongue muscles in old rats SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article; Proceedings Paper CT 106th Annual Meeting of the American-Academy-of-Otolaryngology-Head-and-Neck-Surgery CY SEP 22-25, 2002 CL SAN DIEGO, CA SP Amer Acad Otolaryngol Head & Neck Surg DE aging; deglutition disorder; muscle contraction; tongue ID AGE-RELATED-CHANGES; NEUROMUSCULAR-JUNCTIONS; GENIOGLOSSUS MUSCLE; MEN; STIMULATION; PHARYNGEAL; MORPHOLOGY; FIBERS; FORCE AB Objectives: Fatigue and weakness are well-known signs of aging that are related to sarcopenia, or loss of skeletal muscle mass, organization, and strength. Sarcopenia may affect swallowing. The tongue plays a vital role in swallowing, but there is limited knowledge regarding age-related changes in lingual muscle contractile properties. Our purpose was to determine whether alterations in tongue force, temporal features of tongue muscle contraction, and fatigability are manifested as a function of aging in old rats. Methods: We evaluated tongue muscle contractile properties in young and old Fischer 344/Brown Norway rats. Contractions were elicited via bilateral electrical stimulation of the hypoglossal nerves. Results: Maximum tongue forces and fatigability were-not significantly altered in old animals, but aging was associated with significantly longer twitch contraction time and longer half-decay recovery time intervals (p <.01). Conclusions: The results indicated that old animals generated sufficient maximum tongue forces, but were slower in achieving these forces than young animals. These findings are consistent with reports of altered temporal parameters of tongue actions during swallowing in humans, and suggest that a disruption in the timing of muscle contraction onset and recovery may contribute to the altered tongue kinetics observed with aging. C1 Univ Wisconsin, Clin Sci Ctr, Madison, WI 53792 USA. Univ Wisconsin, Dept Surg, Div Otolaryngol Head & Neck Surg, Madison, WI 53792 USA. Univ Wisconsin, Dept Surg, Dept Biostat & Med Informat, Madison, WI 53792 USA. William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. Jikei Univ, Dept Otolaryngol Head & Neck Surg, Tokyo, Japan. RP Connor, NP (reprint author), Univ Wisconsin, Clin Sci Ctr, Room K4-711,600 Highland Ave, Madison, WI 53792 USA. FU NIDCD NIH HHS [R01DC005935] NR 32 TC 19 Z9 20 U1 4 U2 5 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD OCT PY 2005 VL 114 IS 10 BP 799 EP 803 PG 5 WC Otorhinolaryngology SC Otorhinolaryngology GA 972AW UT WOS:000232427200010 PM 16285271 ER PT J AU Graham, BB Mathisen, DJ Mark, EJ Takvorian, RW AF Graham, BB Mathisen, DJ Mark, EJ Takvorian, RW TI Primary pulmonary lymphoma SO ANNALS OF THORACIC SURGERY LA English DT Article ID B-CELL LYMPHOMA; TISSUE LYMPHOMAS; LUNG; CLASSIFICATION; DISORDERS; NEOPLASMS AB Background. Primary pulmonary lymphoma is a rare disease. The clinical characteristics, methods of treatment, and outcomes are not well elucidated. Methods. A retrospective review of primary pulmonary lymphoma cases at a single institution from 1990 to 2002 was performed. Results. Eighteen patients were included, with a mean follow-up of 2.9 years. Fourteen patients had mucosa-associated lymphoid tissue (MALT) lymphoma, 2 had large cell transformation of sheet cells in MALT lymphoma, and 1 each had Hodgkin's disease and follicular lymphoma. Computed tomography-guided biopsy was diagnostic in only two of eight attempts. Eleven patients had disease confined to the pulmonary parenchyma, and 7 had parenchymal disease as well as mediastinal lymphadenopathy. Treatment methods included observation only (n = 1), surgery only (n = 6), surgery plus chemotherapy (n = 8), surgery plus radiotherapy (n = 1), and surgery plus chemotherapy plus radiotherapy (n = 2). Kaplan-Meier estimate of median time to disease recurrence or death was 6 years. Only 1 patient died of disease-related causes. Patients who had bilateral disease were more likely to have recurrent disease or death (P = 0.03). Conclusions. A wide range of treatments were used for patients with generally MALT lymphoma, resulting in good outcomes, and recurrent disease was well controlled. C1 Massachusetts Gen Hosp, Dept Thorac Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02114 USA. RP Graham, BB (reprint author), Univ Colorado, Hlth Sci Ctr, Campus Box B-177, Denver, CO 80262 USA. EM brian.graham@uchsc.edu NR 21 TC 35 Z9 52 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD OCT PY 2005 VL 80 IS 4 BP 1248 EP 1253 DI 10.1016/j.athoracsur.2005.04.014 PG 6 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 972GK UT WOS:000232442100013 PM 16181848 ER PT J AU Allan, JS Donahue, DM Garrity, JM AF Allan, JS Donahue, DM Garrity, JM TI Rheumatoid pleural effusion in the absence of arthritic disease SO ANNALS OF THORACIC SURGERY LA English DT Article ID PLEURITIS; GLUCOSE; FLUID; FEATURES; CYTOLOGY; LESIONS AB Rheumatoid pleural effusion is an unusual complication of rheumatoid disease that typically presents subsequent to other more common manifestations of rheumatoid illness. The case of a 72-year-old woman with a rheumatoid pleural effusion is discussed. The patient presented with dyspnea, but without any history of rheumatoid arthritis. The patient was treated by thoracentesis, followed by video-thoracoscopy and pulmonary decortication. Postoperatively, the patient's effusion partially reaccumulated. Steroid therapy resulted in prompt and permanent resolution of the effusion. The patient remains asymptomatic 1 year after her presentation. The biochemical, serologic, and cytologic characteristics of rheumatoid effusions are reviewed. C1 Massachusetts Gen Hosp, Dept Surg, Div Thorac Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Allan, JS (reprint author), Massachusetts Gen Hosp, Dept Surg, Div Thorac Surg, 55 Fruit St,Blake 1570, Boston, MA 02114 USA. EM jallan@partners.org NR 14 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD OCT PY 2005 VL 80 IS 4 BP 1519 EP 1521 DI 10.1016/j.athoracsur.2004.04.048 PG 3 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 972GK UT WOS:000232442100064 PM 16181910 ER PT J AU Wexler, HM Engel, AE Glass, D Li, CD AF Wexler, HM Engel, AE Glass, D Li, CD TI In vitro activities of doripenem and comparator agents against 364 anaerobic clinical isolates SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID VIVO ANTIBACTERIAL ACTIVITIES; PSEUDOMONAS-AERUGINOSA; BACTEROIDES-FRAGILIS; PARENTERAL CARBAPENEM; BILOPHILA-WADSWORTHIA; ANTIMICROBIAL AGENTS; PENEM ANTIBIOTICS; SPIRAL GRADIENT; AGAR DILUTION; END-POINT AB The in vitro activities of doripenem against 364 anaerobic isolates were measured and compared to those of ertapenem, imipenem, meropenem, ceftriaxone, and levotloxacin. All of the carbapenems were active against nearly all Bacteroides fragilis group isolates. Doripenem was either comparable to or slightly less active than imipenem and meropenem against most isolates but more active than the other penems against Clostridium difficile. Doripenem appears to have excellent activity against a broad range of anaerobes. C1 Greater Los Angeles Vet Adm Hlth Care Serv, Med & Res Serv, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. RP Wexler, HM (reprint author), Wadsworth Anaerobe Lab, Bldg 304,Room E3-224,GLAVAHCS 691-151J, Los Angeles, CA 90073 USA. EM hwexler@ucla.edu NR 20 TC 37 Z9 38 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD OCT PY 2005 VL 49 IS 10 BP 4413 EP 4417 DI 10.1128/AAC.49.10.4413-4417.2005 PG 5 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 969OW UT WOS:000232244700067 PM 16189137 ER PT J AU Rabito, CA Chen, Y Schomacker, KT Modell, MD AF Rabito, CA Chen, Y Schomacker, KT Modell, MD TI Optical, real-time monitoring of the glomerular filtration rate SO APPLIED OPTICS LA English DT Article ID CHRONIC RENAL-INSUFFICIENCY; INJECTION INULIN-CLEARANCE; SERUM CREATININE; FAILURE; CHILDREN; MARKER; DTPA AB An easy and accurate assessment of the renal function is a critical requirement for detecting the initial functional decline of the kidney induced by acute or chronic renal disease. A method for measuring the glomerular filtration rate is developed with the accuracy of clearance techniques and the convenience of plasma creatinine. The renal function is measured in rats as the rate of clearance determined from time-resolved transcutaneous fluorescence measurements of a new fluorescent glomerular filtration agent. The agent has a large dose-safety coefficient and the same space distribution and clearance characteristics as iothalamate. This new approach is a convenient and accurate way to perform real-time measurements of the glomerular filtration rate to detect early kidney disease before the renal function becomes severely and irreversibly compromised. (c) 2005 Optical Society of America. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. DiametRx Inc, Natick, MA 01760 USA. RP Rabito, CA (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM crabito@partners.org FU NIDDK NIH HHS [R42DK55964] NR 36 TC 24 Z9 25 U1 0 U2 1 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1559-128X EI 2155-3165 J9 APPL OPTICS JI Appl. Optics PD OCT 1 PY 2005 VL 44 IS 28 BP 5956 EP 5965 DI 10.1364/AO.44.005956 PG 10 WC Optics SC Optics GA 968TV UT WOS:000232186200014 PM 16231803 ER PT J AU Biederman, J Monuteaux, MC Kendrick, E Klein, KL Faraone, SV AF Biederman, J Monuteaux, MC Kendrick, E Klein, KL Faraone, SV TI The CBCL as a screen for psychiatric comorbidity in paediatric patients with ADHD SO ARCHIVES OF DISEASE IN CHILDHOOD LA English DT Article ID CHILD-BEHAVIOR CHECKLIST; ATTENTION-DEFICIT HYPERACTIVITY; DEFICIT/HYPERACTIVITY DISORDER; ANXIETY DISORDERS; SAMPLE; DIAGNOSES; SCALES; PSYCHOPATHOLOGY; CONVERGENCE; DEPRESSION AB Aims: To examine the informativeness of the Child Behavior Checklist ( CBCL) as a screening tool to identify comorbid and non-comorbid cases of attention deficit hyperactivity disorder ( ADHD) in a paediatrically referred population. It was hypothesised that specific scales of the CBCL would help identify specific comorbidities within ADHD cases in the primary care setting. Methods: The sample consisted of children and adolescents 6 - 17 years old of both genders with ADHD ( n = 121). A receiver operating curve ( ROC) approach was used to determine which CBCL scales best differentiated between ADHD cases with and without its comorbidities with conduct, anxiety, and mood disorders. Results: ROC analysis showed that the CBCL Delinquent Behavior and Aggressive Behavior scales predicted the structured interview derived diagnoses of conduct and bipolar disorder, the Anxious/Depressed and Aggressive Behavior scales predicted major depression, and the Anxious/ Depressed and Attention problems scales predicted anxiety disorders. Conclusions: These results extend to a paediatrically referred population with previously reported findings in psychiatric samples documenting good convergence between structured interview diagnoses and syndrome congruent CBCL scales. These findings support the utility of the CBCL as a screening tool for the identification of psychiatric comorbidity in ADHD youth in the primary care setting. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Res Program, Boston, MA 02114 USA. SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Res Program, Yawkey Ctr Patient Care,YAW,6A,6900,32 Fruit St, Boston, MA 02114 USA. EM jbiederman@partners.org OI Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [R01MH-41314] NR 37 TC 55 Z9 57 U1 2 U2 7 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-9888 J9 ARCH DIS CHILD JI Arch. Dis. Child. PD OCT PY 2005 VL 90 IS 10 BP 1010 EP 1015 DI 10.1136/adc.2004.056937 PG 6 WC Pediatrics SC Pediatrics GA 966NM UT WOS:000232026700009 PM 16177156 ER PT J AU O'Brien, CP AF O'Brien, CP TI Adolescent opioid abuse SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article C1 Univ Penn, Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. RP O'Brien, CP (reprint author), Univ Penn, Philadelphia VA Med Ctr, 3900 Chestnut St, Philadelphia, PA 19104 USA. EM obrien@mail.trc.upenn.edu NR 1 TC 2 Z9 2 U1 0 U2 0 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 1165 EP 1165 DI 10.1001/archpsyc.62.10.1165 PG 1 WC Psychiatry SC Psychiatry GA 972CD UT WOS:000232430600012 PM 16203962 ER PT J AU Scarmeas, N Brandt, J Albert, M Hadjigeorgiou, G Papadimitriou, A Dubois, B Sarazin, M Devanand, D Honig, L Marder, K Bell, K Wegesin, D Blacker, D Stern, Y AF Scarmeas, N Brandt, J Albert, M Hadjigeorgiou, G Papadimitriou, A Dubois, B Sarazin, M Devanand, D Honig, L Marder, K Bell, K Wegesin, D Blacker, D Stern, Y TI Delusions and hallucinations are associated with worse outcome in Alzheimer disease SO ARCHIVES OF NEUROLOGY LA English DT Article ID LEWY-BODY VARIANT; PSYCHIATRIC-SYMPTOMS; EXTRAPYRAMIDAL SIGNS; COGNITIVE DECLINE; PSYCHOPATHOLOGICAL FEATURES; PSYCHOLOGICAL SYMPTOMS; FUNCTIONAL DECLINE; SENILE DEMENTIA; PROBABLE AD; PREDICTORS AB Background: Delusions and hallucinations are common in Alzheimer disease (AD) and there are conflicting reports regarding their ability to predict cognitive decline, functional decline, and institutionalization. According to all previous literature, they are not associated with mortality. Objective: To examine whether the presence of delusions or hallucinations has predictive value for important outcomes in AD. Design, Setting, and Participants: A total of 456 patients with AD at early stages (mean Folstein Mini-Mental State Examination [MMSE] score of 21 of 30 at entry) were recruited and followed up semiannually for up to 14 years (mean, 4.5 years) in 5 university-based AD centers in the United States and Europe. Using the Columbia University Scale for Psychopathology in AD (administered every 6 months, for a total of 3266 visit-assessments, average of 7.2 per patient), the presence of delusions and hallucinations was extracted and examined as time-dependent predictors in Cox models. The models controlled for cohort effect, recruitment center, informant status, sex, age, education, a comorbidity index, baseline cognitive and baseline functional performance, behavioral symptoms, and use of neuroleptics and cholinesterase inhibitors. Main Outcome Measures: Cognitive (Columbia MMSE score of <= 20/57 [approximate Folstein MMSE score of <= 10/30]), functional (Blessed Dementia Rating Scale [parts I and III score of 2 10), institutionalization equivalent index, and death. Results: During the full course of follow-up, 38% of patients reached the cognitive, 41% the functional, 54% the institutionalization, and 49% the mortality end point. Delusions were noted for 34% of patients at baseline and 70% at any evaluation. Their presence was associated with increased risk for cognitive (risk ratio [RR], 1.50; 95% confidence interval [CI], 1.07-2.08) and functional decline (RR, 1.41; 95% CI, 1.02-1.94). Hallucinations were present in 7% of patients at initial visit and in 33% at any visit. Their presence was associated with increased risk for cognitive decline (RR, 1.62; 95% CI, 1.06-2.47), functional decline (RR, 2.25; 95% Cl, 1.54-2.27), institutionalization (RR, 1.60; 95% CI, 1.13-2.28), and death (RR, 1.49; 95% Cl, 1.03-2.14). Conclusions: Delusions and hallucinations are very common in AD and predict cognitive and functional decline. Presence of hallucinations is also associated with institutionalization and mortality. C1 Columbia Univ, Coll Phys & Surg, Cognit Neurosci Div,Gertrude H Sergievsky Ctr, Taub Inst Res Alzheimers Dis & Aging Brain, New York, NY USA. Columbia Univ, Coll Phys & Surg, Dept Neurol, New York, NY USA. Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY USA. Johns Hopkins Univ, Dept Psychiat & Behav Sci, Baltimore, MD USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02115 USA. Hosp Salpetriere, Dept Neurol, Paris, France. Univ Thessaly, Dept Neurol, Larisa, Greece. RP Scarmeas, N (reprint author), Columbia Univ, Med Ctr, Presbyterian Hosp, 622 W 168th St,19th Floor, New York, NY 10032 USA. EM ns257@columbia.edu OI Brandt, Jason/0000-0001-7381-6244 FU NCRR NIH HHS [M01 RR000645, RR00645]; NIA NIH HHS [P50-AG 08702, P50 AG008702, R01 AG007370, R01 AG007370-07, Z01 AG007370] NR 56 TC 123 Z9 126 U1 1 U2 7 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD OCT PY 2005 VL 62 IS 10 BP 1601 EP 1608 DI 10.1001/archneur.62.10.1601 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 973DK UT WOS:000232502900016 PM 16216946 ER PT J AU Yueh, B McDowell, JA Collins, M Souza, PE Loovis, CF Deyo, RA AF Yueh, B McDowell, JA Collins, M Souza, PE Loovis, CF Deyo, RA TI Development and validation of the effectiveness of the auditory rehabilitation scale SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article ID QUALITY-OF-LIFE; HEARING PERFORMANCE INVENTORY; HANDICAP INVENTORY; COMMUNICATION PROFILE; RANDOMIZED TRIAL; OLDER-ADULTS; AID BENEFIT; TIME-COURSE; AMPLIFICATION; IMPAIRMENT AB Objective: To develop a new scale of hearing-related function and quality of life in patients with hearing Aids that addresses overlooked concerns, such as hearing-aid comfort, convenience, and cosmetic appearance, that may influence hearing-aid adherence while maintaining brevity and sensitivity to clinical change. Design: Prospective, multicenter instrument validation. Setting: Four diverse sites in Washington State, including 2 private practices, I university setting, and 1 Veterans Affairs hospital. Patients: Seventy-eight patients with hearing aids. Interventions: We created 2 modules in the Effectiveness of Auditory Rehabilitation (EAR) scale. The first module (Inner EAR) covers intrinsic hearing issues such as hearing in quiet and hearing in noise and is administered both before and after treatment. The second module (Outer EAR) covers extrinsic (hearing-aid related) issues such as comfort, appearance, and convenience and is administered after hearing-aid fitting. Main Outcome Measures: Both scales were developed and validated in 3 stages. Stage I used a qualitative approach from multiple data sources to develop preliminary instruments. Stage 2 used approaches from classic test theory to reduce the number of items and psychometrically validate the instruments. Stage 3 examined the responsiveness or sensitivity to clinical change. Results: A 10-item Inner EAR module and a 10-item Outer EAR module were created and validated. Internal consistency of individual domains (Cronbach alpha=0.85 and 0.72, respectively) and test-retest reliability (intraclass correlation coefficients=0.76 and 0.81, respectively) were excellent. Evidence of construct validity included concurrent validity with other hearing scales and global visual analog scales, discriminant validity with dizziness handicap correlation with hearing-aid adherence, and confirmatory factor analyses., Both scales had strong evidence of responsiveness (sensitivity to change), with higher effect sizes and Guyatt responsiveness statistics than the. 2 widely used hearing scales in this study. The scales took an average of 5 minutes to complete. Conclusions: The EAR scale is a valid and reliable mea sure of the effectiveness of amplification in the treatment of sensorineural hearing loss. It addresses the range of issues that are of importance to hearing-aid patients. The scales have excellent psychometric properties, are more responsive than several widely used hearing scales, and are minimally burdensome for patients to complete. The EAR may be a valuable outcome measure in future studies of both existing hearing aids and newer hearing-aid technologies, such as bone-anchored aids or middle ear implants. C1 VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Serv, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Hlth Serv Res & Dev Serv, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Surg & Perioperat Care Serv, Seattle, WA 98108 USA. Univ Washington, Dept Otolaryngol Head & Neck Surg, Seattle, WA 98195 USA. Univ Washington, Dept Speech & Hearing Sci, Seattle, WA 98195 USA. Univ Washington, Dept Internal Med, Seattle, WA 98195 USA. Univ Washington, Ctr Cost & Outcomes Res, Seattle, WA 98195 USA. Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA. RP Yueh, B (reprint author), VA Puget Sound Hlth Care Syst, Surg Serv, 1120TO,1660 S Columbian Way, Seattle, WA 98108 USA. EM byueh@u.washington.edu OI Yueh, Bevan/0000-0003-1380-1053 FU NIA NIH HHS [R-03 AG18150] NR 42 TC 13 Z9 13 U1 5 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD OCT PY 2005 VL 131 IS 10 BP 851 EP 856 DI 10.1001/archotol.131.10.851 PG 6 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 972BG UT WOS:000232428200002 PM 16230585 ER PT J AU Feinbloom, D Bauer, KA AF Feinbloom, D Bauer, KA TI Assessment of hemostatic risk factors in predicting arterial thrombotic events SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Review DE arterial; thrombosis; atherosclerosis; hemostasis; risk factors ID C-REACTIVE PROTEIN; PLASMINOGEN-ACTIVATOR INHIBITOR-1; CORONARY-HEART-DISEASE; GLYCOPROTEIN IB-ALPHA; SYSTEMIC-LUPUS-ERYTHEMATOSUS; LOW-DENSITY-LIPOPROTEIN; FACTOR-V-LEIDEN; MEASURING PLASMA-FIBRINOGEN; ACUTE MYOCARDIAL-INFARCTION; BASE-LINE CHARACTERISTICS AB Arterial thrombosis results from endovascular injury and, to a lesser extent, alterations in hemostatic equilibrium. Although multiple hereditary and acquired hemostatic risk factors have been described in the pathophysiology of venous thrombosis, the degree and type of abnormalities that contribute to arterial thrombosis are less well understood. Endothelial cell injury with the elaboration of proinflammatory mediators stimulates the process of arterial thrombosis. Although this is most often the result of endovascular injury attributable to atherosclerotic disease, other disease states can elicit a similar response as well. Similarly, once thrombosis has been initiated, variations in the activity of coagulation proteins and endogenous anticoagulants, as well as the kinetics of platelet aggregation, may alter the effectiveness of thrombus formation. Epidemiological studies have identified several acquired or inherited states that may result in endothelial damage or altered hemostatic equilibrium, thereby predisposing patients to arterial thrombosis. These include hyperhomocysteinemia, elevated C-reactive protein, antiphospholipid antibodies, elevated fibrinogen, Factor VII, plasminogen activator inhibitor-1 (PAI-1), hereditary thrombophilias, and platelet hyper-reactivity. This review explores our present understanding of these risk factors in the development of arterial thrombotic events. At present, the literature supports a role for hyperhomocysteinemia, elevated C-reactive protein, and elevated fibrinogen as risk factors for arterial thrombosis. Similarly, the literature suggests that lupus anticoagulants and, to a lesser extent, elevated titers of cardiolipin IgG antibodies predispose to arterial vascular events. In certain subsets of patients, including those with concomitant cardiac risk factors, < 55 years of age, and women, hereditary thrombophilias such as carriership of the factor V Leiden and the prothrombin G20210A mutations may confer a higher risk of arterial thrombosis. However, the data on Factor VII, PAI-1, and platelet receptor polymorphisms are contradictory or lacking. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA USA. RP Bauer, KA (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med, 330 Brookline Ave, Boston, MA 02115 USA. EM kbauer@bidmc.harvard.edu NR 127 TC 72 Z9 77 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD OCT PY 2005 VL 25 IS 10 BP 2043 EP 2053 DI 10.1161/01.ATV.0000181762.31694.da PG 11 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 969JX UT WOS:000232231500006 PM 16100033 ER PT J AU Virmani, R Kolodgie, FD Burke, AP Finn, AV Gold, HK Tulenko, TN Wrenn, SP Narula, J AF Virmani, R Kolodgie, FD Burke, AP Finn, AV Gold, HK Tulenko, TN Wrenn, SP Narula, J TI Atherosclerotic plaque progression and vulnerability to rupture - Angiogenesis as a source of intraplaque hemorrhage SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Review DE angiogenesis; plaque rupture; sudden coronary death; free cholesterol; hemorrhage ID ENDOTHELIAL GROWTH-FACTOR; TOLL-LIKE RECEPTOR-4; VASA VASORUM; CORONARY-ARTERIES; SIGNALING PATHWAY; FACTOR EXPRESSION; FREE-CHOLESTEROL; ISCHEMIC DEATH; UP-REGULATION; FOAM CELLS AB Observational studies of necrotic core progression identify intraplaque hemorrhage as a critical factor in atherosclerotic plaque growth and destabilization. The rapid accumulation of erythrocyte membranes causes an abrupt change in plaque substrate characterized by increased free cholesterol within the lipid core and excessive macrophage infiltration. Neoangiogenesis is associated closely with plaque progression, and microvascular incompetence is a likely source of intraplaque hemorrhage. Intimal neovascularization is predominantly thought to arise from the adventitia, where there are a plethora of pre-existing vasa vasorum. In lesions that have early necrotic cores, the majority of vessels invading from the adventitia occur at specific sites of medial wall disruption. A breech in the medial wall likely facilitates the rapid in-growth of microvessels from the adventitia, and exposure to an atherosclerotic environment stimulates abnormal vascular development characterized by disorganized branching and immature endothelial tubes with "leaky" imperfect linings. This network of immature blood vessels is a viable source of intraplaque hemorrhage providing erythrocyte-derived phospholipids and free cholesterol. The rapid change in plaque substrate caused by the excessive accumulation of erythrocytes may promote the transition from a stable to an unstable lesion. This review discusses the potential role of intraplaque vasa vasorum in lesion instability as it relates to plaque rupture. C1 Int Registry Pathol, CVPath, Gaithersburg, MD 20878 USA. Univ Maryland, Dept Pathol, Baltimore, MD 21201 USA. Massachusetts Gen Hosp, Dept Internal Med, Cardiac Unit, Boston, MA 02114 USA. Thomas Jefferson Univ, Dept Surg, Philadelphia, PA 19107 USA. Drexel Univ, Dept Chem Engn, Philadelphia, PA 19104 USA. Univ Calif Irvine, Dept Cardiol, Irvine, CA USA. RP Virmani, R (reprint author), Int Registry Pathol, CVPath, 19 Firstfield Rd, Gaithersburg, MD 20878 USA. EM rvirmani@cvpath.org FU NHLBI NIH HHS [R01 HL61799-02] NR 73 TC 663 Z9 712 U1 2 U2 25 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD OCT PY 2005 VL 25 IS 10 BP 2054 EP 2061 DI 10.1161/01.ATV.0000178991.71605.18 PG 8 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 969JX UT WOS:000232231500007 PM 16037567 ER PT J AU Ibrahim, SA Stone, RA Han, XY Cohen, P Fine, MJ Henderson, WG Khuri, SF Kwoh, CK AF Ibrahim, SA Stone, RA Han, XY Cohen, P Fine, MJ Henderson, WG Khuri, SF Kwoh, CK TI Racial/ethnic differences in surgical outcomes in veterans following knee or hip arthroplasty SO ARTHRITIS AND RHEUMATISM LA English DT Article ID SURGEON PROCEDURE VOLUME; RISK ADJUSTMENT; UNITED-STATES; RHEUMATOID-ARTHRITIS; JOINT REPLACEMENT; MEDICARE PATIENTS; HEALTH-CARE; QUALITY; OSTEOARTHRITIS; MORTALITY AB Objective. The utilization of joint arthroplasty for knee or hip osteoarthritis varies markedly by patient race/ethnicity. Because of concerns about surgical risk, black patients are less willing to consider this treatment. There are few published race/ethnicity-specific data on joint arthroplasty outcomes. The present study was undertaken to examine racial/ethnic differences in mortality and morbidity following elective knee or hip arthroplasty. Methods. Using information from the Veterans Administration National Surgical Quality Improvement Program database, data on 12,108 patients who underwent knee arthroplasty and 6,703 patients who underwent hip arthroplasty over a 5-year period were analyzed. Racial/ethnic differences were determined using prospectively collected data on patient characteristics, procedures, and short-term outcomes. The main outcome measures were risk-adjusted 30-day mortality and complication rates. Results. Adjusted rates of both non-infection-related and infection-related complications after knee arthroplasty were higher among black patients compared with white patients (relative risk [RR] 1.50, 95% confidence interval [95% CI] 1.08-2.10 and RR 1.42, 95% CI 1.06-1.90, respectively). Hispanic patients had a significantly higher risk of infection-related complications after knee arthroplasty (RR 1.64, 95% Cl 1.082.49) relative to otherwise similar white patients. Race/ethnicity was not significantly associated with the risk of non-infection-related complications (RR 0.97, 95% CI 0.68-1.38 in blacks; RR 1.18, 95% CI 0.60-2.30 in Hispanics) or infection-related complications (RR 1.27, 95% Cl 0.91-1.78 in blacks; RR 1.22, 95% CI 0.63-2.36 in Hispanics) after hip arthroplasty. The overall 30-day mortality was 0.6% following knee arthroplasty and 0.7% following hip arthroplasty, with no significant differences by race/ethnicity observed for either procedure. Conclusion. Although absolute risks of complication are low, our findings indicate that, after adjustment, black patients have significantly higher rates of infection-related and non-infection-related complications following knee arthroplasty, compared with white patients. In addition, adjusted rates of infection - related complications after knee arthroplasty are higher in Hispanic patients than in white patients. Such differences between ethnic groups are not seen following hip arthroplasty. These groups do not appear to differ significantly in terms of post-arthroplasty mortality rates. C1 VA Pittsburgh Healthcare Syst, Ctr Hlth Equal Res & Promot, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Pittsburgh, PA USA. Univ Colorado, Denver, CO 80202 USA. VA Natl Surg Qual Improvement Program, Boston, MA USA. RP Ibrahim, SA (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equal Res & Promot, 151-C, Pittsburgh, PA 15240 USA. EM said.ibrahim2@med.va.gov NR 36 TC 69 Z9 70 U1 1 U2 3 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 3143 EP 3151 DI 10.1002/art.21304 PG 9 WC Rheumatology SC Rheumatology GA 973UT UT WOS:000232548800024 PM 16200594 ER PT J AU Wang, C Ghalambor, N Zarins, B Warner, JJP AF Wang, C Ghalambor, N Zarins, B Warner, JJP TI Arthroscopic versus open bankart repair: Analysis of patient subjective outcome and cost SO ARTHROSCOPY-THE JOURNAL OF ARTHROSCOPIC AND RELATED SURGERY LA English DT Article DE shoulder instability; arthroscopic repair; outcomes; cost analysis ID 6-YEAR FOLLOW-UP; ANTERIOR STABILIZATION; GLENOID LABRUM; SHOULDER; INSTABILITY; LESIONS; TACK AB Purpose: Although the comparative efficacy of open and arthroscopic Bankart repair remains a matter of debate, little data exist on relative costs. We analyzed the patient outcomes, cost, and resource utilization of both procedures to determine if differences exist between open versus arthroscopic Bankart repair. Type of Study: Retrospective case-control study. Methods: We compared 22 patients who had open Bankart repair with 20 patients who had arthroscopic Bankart repair. Total operating times and all charges were obtained from records. Patients were evaluated using the American Shoulder and Elbow Surgeons (ASES) shoulder score, and any recurrence of dislocation was noted at minimum 24-month follow-up. Results: For arthroscopic Bankart repairs, operating times were shorter, but operating room equipment charges were greater. Overall charges were greater for open repairs as all open repair patients were admitted postoperatively. ASES shoulder scores were not significantly different between treatment groups. Four of 17 evaluable patients with open Bankart repair (including I shoulder in a patient who underwent bilateral repairs) had recurrent dislocation. One of the 18 evaluable patients with arthroscopic Bankart repair had recurrent dislocation. Conclusions: Arthroscopic Bankart repair as same-day surgery has lower overall charges than open repair, although this difference would be negligible if all patients went home immediately after surgery. Level of Evidence: Level III, therapeutic, retrospective cohort study. C1 Harvard Univ, Sch Med,Massachusetts Gen Hosp, Dept Orthopaed, Yawkey Ctr Outpatient Care, Boston, MA 02114 USA. Loma Linda Univ, Dept Orthopaed Surg, Loma Linda, CA 92350 USA. RP Wang, C (reprint author), Harvard Univ, Sch Med,Massachusetts Gen Hosp, Dept Orthopaed, Yawkey Ctr Outpatient Care, Suite 3200,3G,Room 3-046, Boston, MA 02114 USA. EM jwarner@partners.org NR 23 TC 31 Z9 33 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 0749-8063 J9 ARTHROSCOPY JI Arthroscopy PD OCT PY 2005 VL 21 IS 10 BP 1219 EP 1222 DI 10.1016/j.arthro.2005.07.004 PG 4 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 978XZ UT WOS:000232907700010 PM 16226650 ER PT J AU Ueno, T Omura, T Takahashi, T Matsumoto, H Takahashi, Y Kakita, A Yamashina, S AF Ueno, T Omura, T Takahashi, T Matsumoto, H Takahashi, Y Kakita, A Yamashina, S TI Liver transplantation using liver grafts preserved under high pressure SO ARTIFICIAL ORGANS LA English DT Article DE organ preservation; cold storage under high pressure; liver transplantation ID RAT-LIVER; CRYOPRESERVATION; OOCYTE; PRINCIPLES; STRATEGIES; DAMAGE; FLUID; CELL AB To extend organ preservation time, we attempted to establish a unique method of maintaining a preservation solution in a stable unfrozen state below its freezing point by pressurizing the solution. Livers removed from Lewis rats (RT11) were stored in UW solution pressurized at the prescribed pressure. After the termination of preservation, orthotopic liver transplantation was performed. Experiment 1: Liver grafts were pressurized up to 30, 40, 50, and 70 MPa and preserved at 0 degrees C for 60 min. Experiment 2: Liver grafts were compressed at a rate of 1.32 or 0.04 MPa/s to 35 MPa and preserved for 60 min at 0 degrees C. Experiments 3 and 4: Liver grafts were pressurized up to 5, 10, 20, and 30 MPa and preserved at 2 degrees C (Exp. 3), -3 degrees C or -4 degrees C (Exp. 4) for 5 h. All rats transplanted with livers pressurized up to 30 MPa ( Exp. 1), all rats in the 5 MPa and control groups at - 2 degrees C (Exp. 3), and all rats in the 5 MPa group at -3 degrees C (Exp. 4) survived for 2 weeks. In light microscopy, diffuse hemorrhage and vacuolar degeneration of hepatocytes were observed in a pressure-dependent manner. Liver grafts preserved under pressurized, subzero nonfrozen condition have sufficient function to sustain the life of rats after orthotopic transplantation. C1 Kitasato Univ, Sch Med, Dept Surg, Sagamihara, Kanagawa 228, Japan. Higashiyamato Gen Hosp, Dept Surg, Sagamihara, Kanagawa, Japan. RP Ueno, T (reprint author), Massachusetts Gen Hosp, Transplantat Unit, Surg Serv, WACC, Suite 478,15 Parkman St, Boston, MA 02114 USA. EM tueno@partners.org NR 33 TC 2 Z9 2 U1 1 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0160-564X J9 ARTIF ORGANS JI Artif. Organs PD OCT PY 2005 VL 29 IS 10 BP 849 EP 855 DI 10.1111/j.1525-1594.2005.00139.x PG 7 WC Engineering, Biomedical; Transplantation SC Engineering; Transplantation GA 967PA UT WOS:000232102500011 PM 16185349 ER PT J AU Lees, AM Deconinck, AE Campbell, BD Lees, RS AF Lees, AM Deconinck, AE Campbell, BD Lees, RS TI Atherin: a newly identified, lesion-specific, LDL-binding protein in human atherosclerosis SO ATHEROSCLEROSIS LA English DT Article DE atherin; atherogenesis; focal LDL retention; arterial wall; proteoglycans ID LOW-DENSITY LIPOPROTEINS; LEUKOCYTE ADHESION MOLECULE; RABBIT ARTERIAL-WALL; ATHEROGENIC LIPOPROTEINS; EXTRACELLULAR-MATRIX; ACCUMULATION; RETENTION; EXPRESSION; TAXILIN; CELLS AB Prolonged retention of LDL in focal, atherosclerosis-prone areas of arteries is a primary event in atherogenesis. To determine whether unrecognized LDL-binding proteins participate in this process, we generated a cDNA expression library from deendothelialized rabbit aorta, a model for early atherosclerosis that shows striking focal LDL retention in healing lesions. Library screening identified a previously unknown, highly conserved, 56 kDa LDL-binding protein that we call atherin. Confocal microscopy of human arteries shows that atherin is present only in atherosclerotic lesions, not in normal intima. Within lesions, atherin is found both in the extracellular compartment and within foam cells. Essentially all extracellular atherin, as well as atherin within foam cells, co-localizes with LDL across the entire spectrum of human disease, from early lesions to advanced plaques. Our results suggest that focal arterial LDL accumulation may be initiated and maintained by binding between LDL and atherin, and that atherin may play a central role in atherogenesis by immobilizing LDL in the arterial wall. (c) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Boston Heart Fdn, Brookline, MA 02445 USA. Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Atherex, LLC, Lincoln, MA USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Lees, AM (reprint author), Boston Heart Fdn, 203 Clinton Rd, Brookline, MA 02445 USA. EM amlees@mit.edu NR 30 TC 6 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 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD OCT PY 2005 VL 182 IS 2 BP 219 EP 230 DI 10.1016/j.atherosclerosis.2005.01.041 PG 12 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 976TM UT WOS:000232756300003 PM 16159594 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 Caetano, SC Olvera, RL Glahn, D Fonseca, M Pliszka, S Soares, JC AF Caetano, SC Olvera, RL Glahn, D Fonseca, M Pliszka, S Soares, JC TI Fronto-limbic brain abnormalities in juvenile onset 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; MRI; MRS; children; adolescents ID MAGNETIC-RESONANCE SPECTROSCOPY; SUBGENUAL PREFRONTAL CORTEX; WHITE-MATTER HYPERINTENSITIES; ANTERIOR CINGULATE CORTEX; TEMPORAL-LOBE STRUCTURES; PROTON MR SPECTROSCOPY; MOOD DISORDERS; I DISORDER; EUTHYMIC PATIENTS; ADOLESCENT PATIENTS AB Background: Advances in brain imaging techniques and cognitive neuropsychology have brought new possibilities for the in vivo study of the pathophysiology of neuropsychiatric disorders, including bipolar disorder (BD), Recently, such studies have been extended to the pediatric age range. Here we review the neuroimaging and neuropsycbological studies conducted in BD children and adolescents. Methods: A review of the peer-reviewed published literature was conducted in Medline for the period of 1966 to April 2005. Results: Magnetic resonance imaging (MPI) and magnetic resonance spectroscopy (MRS) studies suggest abnormalities in fronto-limbic structures in pediatric BD patients, similar to those found in adults. A notable exception in pediatric BD patients is smaller amygdala volumes compared to healthy controls, contrary to what has been reported in most adult studies. Conclusions. Further research evaluating children and adolescents is needed to study the normal neurodevelopmental process and to answer bow and when the illness processes that result in bipolar disorder exert their effects on the developing brain. C1 Univ Texas, Hlth Sci Ctr, Div Mood & Anxiety Disorders, Dept Psychiat, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Radiol, San Antonio, TX 78284 USA. S Texas Vet Hlth Care Syst, Dept Psychiat, Audie L Murphy Div, San Antonio, TX USA. Univ Sao Paulo, Sch Med, Inst Psychiat, Sao Paulo, Brazil. Univ Fed Rio Grande Sul, Sch Med, Psychiat Res Unit, Med Sch Postgrad Program, Porto Alegre, RS, Brazil. RP Soares, JC (reprint author), Univ Texas, Hlth Sci Ctr, Div Mood & Anxiety Disorders, Dept Psychiat, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM soares@uthscsa.edu RI Caetano, Sheila/H-5010-2012 OI Caetano, Sheila/0000-0001-8403-7078 FU NCRR NIH HHS [M01-RR-01346]; NIMH NIH HHS [5 U13 MH64077-03, K23-MH068280, MH01736, MH068662, MH069774] NR 90 TC 27 Z9 29 U1 1 U2 4 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 525 EP 531 DI 10.1016/j.biopsych.2005.04.027 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 978IH UT WOS:000232866300003 PM 16018982 ER PT J AU Doyle, AE Wilens, TE Kwon, A Seidman, LJ Faraone, SV Fried, R Swezey, A Snyder, L Biederman, J AF Doyle, AE Wilens, TE Kwon, A Seidman, LJ Faraone, SV Fried, R Swezey, A Snyder, L Biederman, J TI Neuropsychological functioning in youth with 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 juvenile mania; neuropsychology; pediatric bipolar disorder ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; SUSTAINED ATTENTION; EXECUTIVE FUNCTIONS; COGNITIVE FUNCTION; WORKING-MEMORY; I DISORDER; CHILDREN; MANIA; ADOLESCENTS AB Background: Little is known about the neuropychological status of youth with, bipolar disorder (BPD) or whether cognitive deficits in this population are accounted for by comorbidity with attention deficit/hyperactivity disorder (ADHD). We compared neuropsychological and academic functioning of youth with and without DSM-IV BPD, controlling for effects of comorbid ADHD. Methods: Fifty-seven youth with BPD and 46 healthy control subjects were assessed on a battery of clinical neuropsychological measures including subtests from the Wechsler Intelligence Scales for Children and Adults (Third Editions), the Stroop, the Wisconsin Card Sorting Test, the Ret-Osterreith Complex Figure, an auditory working memory Continuous Performance Test, a measure of verbal learning, and the Wide Range Achievement Test-Third Edition. Results: Bipolar disorder was associated with impairments on subtests reflecting sustained attention, working memory, and processing speed after controlling for ADHD. Additionally, decrements of moderate effect sizes were ound,for measures of interference control, abstract problem solving, and verbal learning but did not meet criteria for statistical significance. Conclusions: After controlling for ADHD, youth with BPD show neuropsychological deficits similar to impairments found in adults with the disorder. Further studies are needed to understand the clinical implications of these impairments as well as their role in the underlying risk for pediatric BPD. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA USA. Massachusetts Mental Hlth Ctr, Boston, MA 02115 USA. SUNY Upstate Med Univ, Syracuse, NY USA. RP Doyle, AE (reprint author), Massachusetts Gen Hosp, Child Psychiat Serv, YAW 6900,55 Fruit St, Boston, MA 02114 USA. EM doylea@helix.mgh.harvard.edu OI Faraone, Stephen/0000-0002-9217-3982 FU NIDA NIH HHS [R01 DA12945]; NIMH NIH HHS [K08-MH-66072] NR 76 TC 85 Z9 91 U1 1 U2 7 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 540 EP 548 DI 10.1016/j.biopsych.2005.07.019 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 978IH UT WOS:000232866300005 PM 16199011 ER PT J AU Perlis, RH Delbello, MP Miyahara, S Wisniewski, SR Sachs, GS Nierenberg, AA AF Perlis, RH Delbello, MP Miyahara, S Wisniewski, SR Sachs, GS Nierenberg, AA CA STEP-BD Investigators TI Revisiting depressive-prone bipolar disorder: Polarity of initial mood episode and disease course among bipolar I systematic treatment enhancement program for bipolar disorder participants SO BIOLOGICAL PSYCHIATRY LA English DT Article DE bipolar disorder; depression; age of onset; polarity; chronic ID WEEKLY SYMPTOMATIC STATUS; PROSPECTIVE FOLLOW-UP; SUSCEPTIBILITY LOCI; NATURAL-HISTORY; EARLY-ONSET; STEP-BD; AGE; MANIA AB Background: We examined the hypothesis that a first depressive rather than manic episode in bipolar disorder might herald a subsequent course notable for greater burden of depressive symptoms. Methods: We analyzed retrospective data on the polarity of first mood episode obtained from 704 bipolar I subjects entering the multicenter Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) study. Subjects with an initial manic or depressive episode and those in whom both poles occurred within the same year were compared. Results: Depressive-onset bipolar disorder was more common in women and those with earlier onset of illness. Adjusting for these differences. it was significantly associated with more lifetime depressive episodes and a greater proportion of time with depression and anxiety in the year prior to study entry. Conclusions: Polarity of first mood episode may be useful in distinguishing subsets of bipolar patients at risk for a more chronic course. C1 Massachusetts Gen Hosp, Bipolar Clin & Res Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Cincinnati, Coll Med, Cincinnati, OH USA. Univ Pittsburgh, Grad Sch Publ Hlth, Epidemiol Data Ctr, Pittsburgh, PA USA. RP Perlis, RH (reprint author), Massachusetts Gen Hosp, Bipolar Clin & Res Program, ACC 812,12 Parkman St, Boston, MA 02114 USA. EM rperlis@partners.org OI Wisniewski, Stephen/0000-0002-3877-9860 FU NIMH NIH HHS [N01MH80001] NR 19 TC 45 Z9 46 U1 1 U2 2 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 549 EP 553 DI 10.1016/j.biopsych.2005.07.029 PG 5 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 978IH UT WOS:000232866300006 PM 16197928 ER PT J AU Henin, A Biederman, J Mick, E Sachs, GS Hirshfeld-Becker, DR Siegel, RS McMurrich, S Grandin, L Nierenberg, AA AF Henin, A Biederman, J Mick, E Sachs, GS Hirshfeld-Becker, DR Siegel, RS McMurrich, S Grandin, L Nierenberg, AA TI Psychopathology in the offspring of parents with bipolar disorder: A controlled study SO BIOLOGICAL PSYCHIATRY LA English DT Article DE bipolar disorder; high-risk offspring; family study ID DEFICIT HYPERACTIVITY DISORDER; ANXIETY DISORDERS; MAJOR DEPRESSION; DEVELOPMENTAL SUBTYPE; MOOD DISORDERS; PANIC DISORDER; YOUNG-CHILDREN; FOLLOW-UP; ONSET; COMORBIDITY AB Background: To examine the risk for psychopathology in offspring at risk for bipolar disorder and the course of psycbiatric disorders in these youth. Methods: Using structured diagnostic interviews (Structured Clinical Interviewfor DSM-IV[SCID] and Kiddie Schedule for Affective Disorders and Schizophrenia [K-SADS]), psychiatric diagnoses of 117 nonreferred offspring of parents with diagnosed bipolar disorder were compared with those of 171 age- and gender-matched offspring of parents without bipolar disorder or major depression. Results: Compared with offspring of parents without mood disorders, high-risk youth bad elevated rates of major depression and bipolar disorder, anxiety, and disruptive behavior disorders. High-risk offspring also bad signfcantly more impaired Global Assessment of Functioning (GAF) scores, higher rates of psychiatric treatment, and higher rates of placement in special education classes. Disruptive behavior disorders, separation anxiety disorder, generalized anxiety disorder (GAD), social phobia, and depression tended to have their onset in early or middle childhood, whereas bipolar disorder, obsessive-compulsive disorder (OCD), panic disorder, and substance use disorder had onset most frequently in adolescence. Conclusions: These findings support the hypothesis that offspring of parents with bipolar disorder are at significantly increased risk for developing a wide range of severe psychiatric disorders and accompanying dysfunction. Early disruptive behavior and anxiety disorders, as well as early-onset depression, may be useful markers of risk.for subsequent bipolar disorder in high-risk samples. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Harvard Bipolar Res Program, Cambridge, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP Henin, A (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, 185 Alewife Brook Pkwy,Suite 2000, Cambridge, MA 02138 USA. EM ahenin@partners.org OI Mick, Eric/0000-0001-8505-8145 NR 78 TC 104 Z9 107 U1 2 U2 9 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 554 EP 561 DI 10.1016/j.biopsych.2005.06.010 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 978IH UT WOS:000232866300007 PM 16112654 ER PT J AU Hudziak, JJ Althoff, RR Derks, EM Faraone, SV Boomsma, DI AF Hudziak, JJ Althoff, RR Derks, EM Faraone, SV Boomsma, DI TI Prevalence and genetic architecture of child behavior checklist-juvenile bipolar disorder SO BIOLOGICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 50th Annual Meeting of the American-Academy-of-Child-and-Adolescent-Psychiatry CY OCT 14-19, 2003 CL Miami, FL SP Amer Acad Child & Adolescent Psychiat DE child; bipolar affective disorder; CBCL; genetic model; ADHD; twin ID DEFICIT HYPERACTIVITY DISORDER; MANIC SYMPTOMS; ADHD; ADOLESCENTS; ONSET; TWINS; CBCL; COMORBIDITY; DIAGNOSIS AB Background: No consensus has been reached yet on bow best to characterize children with juvenile bipolar disorder (JBD). Several groups have shown that children on the attention problems (AP), aggressive behavior (AGG), and anxious-depressed (AD) syndromes of the Child Behavior Checklist (CBCL) are likely to meet criteria for DSM-JBD. We aimed to use a large population-based twin sample to evaluate the prevalence and genetic architecture of the CBCL-JBD(deviant on AP, AGG, and AD)phenotype and compare these data to children who are deviant on just the CBCL-AP syndrome. Methods: Structural equation modeling (SEM) was applied to CBCL data from 5418, 3562, and 1971 Dutch twin pairs at ages 7, 10, and 12 years. Results: The CBCL-JBD phenotype occurs in similar to 1% of children at each age. Among the children who meet criteria for the CBCL-AP phenotype (similar to 5%), between 13 and 20% also meet criteria for CBCL-JBD. The best SEM for CBCL-JBD includes additive genetic, shared and unique environmental factors. Conclusions: These data suggest that CBCL problems. CBCL-JBD shows familial aggregation due to both genetic and shared environmental factors. C1 Univ Vermont, Dept Psychiat, Div Behav Genet, Burlington, VT 05405 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands. RP Hudziak, JJ (reprint author), Univ Vermont, Dept Psychiat, Div Behav Genet, Given B229, Burlington, VT 05405 USA. EM James.Hudziak@uvm.edu RI Derks, Eske/A-1652-2017; OI Derks, Eske/0000-0002-6292-6883; Hudziak, James/0000-0001-9653-758X; Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [MH58799] NR 35 TC 82 Z9 83 U1 2 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 562 EP 568 DI 10.1016/j.biopsych.2005.03.024 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 978IH UT WOS:000232866300008 PM 16239161 ER PT J AU Mick, E Spencer, T Wozniak, J Biederman, J AF Mick, E Spencer, T Wozniak, J Biederman, J TI Heterogeneity of irritability in attention-deficit/hyperactivity disorder subjects with and without mood disorders SO BIOLOGICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Conference on Pediatric Bipolar Disorder CY APR 02-03, 2004 CL Boston, MA DE ADHD; bipolar disorder; children; irritability ID DEFICIT HYPERACTIVITY DISORDER; ADOLESCENT BIPOLAR DISORDER; PREPUBERTAL CHILDREN; JUVENILE MANIA; ADHD; SYMPTOMS; COMORBIDITY; MISTAKEN; SAMPLE AB Background: We hypothesized that irritability is a heterogeneous symptom distinguished by severity and that attending to this heterogeneity would impact the relationship between irritability and bipolar disorder. Methods: A total of 274 ADHD children were administered the Kiddie Schedule for Affective Disorders and Schizophrenia (Epidemiologic Version) structured diagnostic interview. Three measures of irritability were identified. oppositional defiant disorder (ODD)-type irritability, mad/cranky irritability, and super-angry/grouchy/cranky irritability. Subjects were stratified as having bipolar disorder (n = 30), unipolar depression (n = 100), and no history of depression or bipolar disorder (non-mood-disordered, n = 144). Results: Oppositional defiant disorder-type irritability was very common in all ADHD subjects, was the least impairing, and did not increase the risk of mood disorder. Mad/cranky irritability was common in only ADHD children with a mood disorder, was more impairing than the ODD-type irritability, and was predictive of unipolar depression. Super-angry/grouchy/cranky irritability was common only in ADHD children with bipolar disorder, was the most impairing, and was predictive of both unipolar depression and bipolar disorder. Two percent of the subjects with ODD-type irritability only, 6% of subjects with mad/cranky irritability, and 46% of subjects with super-angry/grouchy/cranky irritability were diagnosed with bipolar disorder. Conclusions: These results challenge the conclusion that irritability is necessarily a poor diagnostic indicator of bipolar disorder in children. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Res Dept, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA USA. Johnson & Johnson Ctr Study Pediat Psychopathol, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Mick, E (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Res Dept, 55 Fruit St Warren 705, Boston, MA 02115 USA. EM mick@helix.mgh.harvard.edu OI Mick, Eric/0000-0001-8505-8145 FU NIMH NIH HHS [KO1 MH065523] NR 27 TC 81 Z9 83 U1 2 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 576 EP 582 DI 10.1016/j.biopsych.2005.05.037 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 978IH UT WOS:000232866300010 PM 16084859 ER PT J AU Wozniak, J Biederman, J Kwon, A Mick, E Faraone, S Orlovsky, K Schnare, L Cargol, C van Grondelle, A AF Wozniak, J Biederman, J Kwon, A Mick, E Faraone, S Orlovsky, K Schnare, L Cargol, C van Grondelle, A TI How cardinal are cardinal symptoms in pediatric bipolar disorder? An examination of clinical correlates SO BIOLOGICAL PSYCHIATRY LA English DT Article DE pediatric; children; bipolar; mania; euphoria; irritability ID DEFICIT HYPERACTIVITY DISORDER; AFFECTIVE-ILLNESS; MANIC SYMPTOMS; JUVENILE MANIA; CHILDREN; ONSET; PHENOTYPE; CHILDHOOD; MOOD; PHENOMENOLOGY AB Background: The main goal of this study was to test whether the hypothesized cardinal symptom of euphoria results in differences in clinical correlates in bipolar youth ascertained with no a priori assumptions about cardinal symptoms. Methods: Subjects (n = 86) satisfying DSM-IV criteria,for bipolar disorder with and without the proposed cardinal symptom of euphoria were compared in their bipolar symptom pattern, functioning and patterns of comorbidity. Results: Among Criterion A (abnormal mood), we found that severe irritability was the predominant abnormal mood rather than euphoria (94% vs. 51%). We also found that among Criterion B items, grandiosity was not uniquely over represented in youth with mania, nor did the rate of grandiosity differ whether irritability or irritability and euphoria were the Criterion A mood symptom. Neither symptom profiled patterns of comorbidity nor measures of functioning differed related to the presence or absence of euphoria. Conclusions: These findings challenge the notion that euphoria represents a cardinal symptom of mania in children. Instead they support the clinical relevance of severe irritability as the most common presentation of mania in the young. They also support the use of unmodified DSM-IV criteria in establishing the diagnosis of mania in pediatric populations. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Boston, MA USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY USA. RP Wozniak, J (reprint author), 185 Alewife Brook Pkwy,Suite 2000, Cambridge, MA 02138 USA. EM jwozniak@partners.org OI Mick, Eric/0000-0001-8505-8145; Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [R01 MH 066237-02, K08 MH0153-03] NR 32 TC 71 Z9 73 U1 2 U2 3 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 583 EP 588 DI 10.1016/j.biopsych.2005.08.014 PG 6 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 978IH UT WOS:000232866300011 PM 16197929 ER PT J AU Biederman, J Mick, E Hammerness, P Harpold, T Aleardi, M Dougherty, M Wozniak, J AF Biederman, J Mick, E Hammerness, P Harpold, T Aleardi, M Dougherty, M Wozniak, J TI Open-label, 8-week trial of olanzapine and risperidone for the treatment of bipolar disorder in preschool-age children SO BIOLOGICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Conference on Pediatric Bipolar Disorder CY APR 02-03, 2004 CL Boston, MA DE atypical antipsychotics; bipolar disorder; children; clinical trial ID MANIA RATING-SCALE; DOUBLE-BLIND; ADOLESCENTS; VALIDITY; PLACEBO; RELIABILITY; VERSION; YOUTHS AB Background: To evaluate short-term safety and efficacy of atypical antipychotics in a single-site, prospective, open-label, 8-week study of risperidone and olanzapine monotherapy in preschoolers with bipolar disorder (BPD). Methods: Risperidone was initiated at an open-label dose of .25 mg/day, increased weekly according to response and tolerability to a maximum does of 2.0 mg/day. Olanzapine was initiated at 1.25 mg/day and increased to no more than 10 mg/day. Results: Thirty-one children aged 4-6 years were treated with olanzapine (n = 15, 6.3 +/- 2.3 mg/day) or risperidone (n = 16 1.4 +/- .5 mg/day). At study end point (week 8 or last observation carried forward), there was a 18.3 +/- 11.9 point (t = -5.6, p < .001) reduction in risperidone-treated subjects and a 12.1 +/- 10.4 point (t = - 4.4, p < .001) reduction in Young Mania Rating Scale (YMRS) scores in olanzapine-treated subjects that did not differ between groups (t = 1.4, p =.2). Response criteria (Clinical Global Impression improvement of "Much" or "Very Much" improved or a YMRS change of >= 30% or more) indicated no difftrence in rate of response with risperidone and olanzapine (69% vs. 53%, X-(1)(2) =.8, p =.4). Conclusions: This prospective open study suggests that treatment with risperidone or olanzapine may result in a rapid reduction of symptoms of mania it? preschool children with BPD. Because of substantial residual symptomatology and adverse effects, however, a pressing need exists to identify additional safe and effective treatments for the management of BPD in this high-risk population. C1 Massachusetts Gen Hosp, Yawkey Ctr Outpatient Care, Pediat Psychopharmacol Res Dept, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Yawkey Ctr Outpatient Care, Pediat Psychopharmacol Res Dept, YAW-6A-6900,32 Fruit St, Boston, MA 02114 USA. EM jbiederman@partners.org OI Mick, Eric/0000-0001-8505-8145 FU NIMH NIH HHS [S U13MH64077-03] NR 16 TC 107 Z9 111 U1 1 U2 3 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 589 EP 594 DI 10.1016/j.biopsych.2005.03-019 PG 6 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 978IH UT WOS:000232866300012 PM 16239162 ER PT J AU McGinnis, LK Zhu, LB Lawitts, JA Bhowmick, S Toner, M Biggers, JD AF McGinnis, LK Zhu, LB Lawitts, JA Bhowmick, S Toner, M Biggers, JD TI Mouse sperm desiccated and stored in trehalose medium without freezing SO BIOLOGY OF REPRODUCTION LA English DT Article; Proceedings Paper CT 37th Annual Meeting of the Society-for-the-Study-of-Reproduction CY AUG 01-04, 2004 CL Univ British Columbia, Vancouver, CANADA SP Soc Study Reprod HO Univ British Columbia DE embryo; fertilization; gamete biology; ICSI; sperm; sperm desiccation; trehalose ID PREFERENTIAL HYDRATION; DRIED SPERMATOZOA; IN-VITRO; CELLS; INJECTION; CHROMATIN; STABILIZATION; TOLERANCE; PLATELETS; PRESERVATION AB Mouse sperm with and without trehalose were desiccated under nitrogen gas and stored at 4 degrees C and 22 degrees C. After rehydration, sperm were injected into oocytes using intracytoplasmic sperm injection and embryonic development was followed. Sperm were dried for 5.0, 6.25, or 7.5 min, stored at 22 degrees C for 1 wk with and without trehalose. The percentages of blastocysts that developed from sperm with trehalose were 51%, 31%, and 20%, respectively, which was significantly higher than sperm without trehalose (10%, 3%, and 5%, respectively). Desiccation and storage in medium with trehalose significantly increased sperm developmental potential compared to medium without trehalose. Sperm dried for 5 min produced more blastocysts than sperm dried for 6.25 or 7.5 min. When sperm were dried in trehalose for 5 min and stored for 1 wk, 2 wk, 1 mo, or 3 mo at 4 degrees C, the percentages of blastocysts were 73%, 84%, 63%, and 39%; whereas those stored at 22 degrees C for I wk, 2 wk, or 1 mo were significantly lower (53%, 17%, and 6%, respectively). Embryos from sperm partially desiccated in trehalose for 5 min and stored at 4 degrees C for I or 3 mo were transferred to 10 pseudopregnant recipients. Implantation rates were 81% and 48%; live fetuses were 26% and 5%, respectively. One of the recipients delivered three live fetuses. The results show that trehalose has a significant beneficial effect in preserving the developmental potential of mouse sperm following partial desiccation and storage at temperatures above freezing. C1 Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med & Surg Serv, Boston, MA 02114 USA. Shriners Hosp Children, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Transgen Mouse Facil, Boston, MA 02115 USA. Univ Massachusetts, Dept Mech Engn, Dartmouth, MA 02747 USA. RP Biggers, JD (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, 240 Longwood Ave, Boston, MA 02115 USA. EM john-biggers@hms.harvard.edu OI McGinnis, Lynda/0000-0001-7910-9655 FU NCRR NIH HHS [1R24RR018934] NR 48 TC 53 Z9 58 U1 1 U2 6 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 627 EP 633 DI 10.1095/biolreprod.105.042291 PG 7 WC Reproductive Biology SC Reproductive Biology GA 967EB UT WOS:000232073200007 PM 15930320 ER PT J AU Shen, Y Zelen, M AF Shen, Y Zelen, M TI Robust modeling in screening studies: estimation of sensitivity and preclinical sojourn time distribution SO BIOSTATISTICS LA English DT Article DE piecewise-constant density function; preclinical duration; screening clinical trials; screening sensitivity; weighted generalized least squares ID BREAST-CANCER DETECTION; DEATH RATES; DISEASE; PROGRAMS; AIDS AB In early-detection clinical trials, quantities such as the sensitivity of the screening modality and the preclinical duration of the disease are important to describe the natural history of the disease and its interaction with a screening program. Assume that the schedule of a screening program is periodic and that the sojourn time in the preclinical state has a piecewise density function. Modeling the preclinical sojourn time distribution as a piecewise density function results in robust estimation of the distribution function. Our aim is to estimate the piecewise density function and the examination sensitivity using both generalized least squares and maximum likelihood methods. We carried out extensive simulations to evaluate the performance of the methods of estimation. The different estimation methods provide complimentary tools to obtain the unknown parameters. The methods are applied to three breast cancer early-detection trials. C1 Univ Texas, MD Anderson Canc Ctr, Dept Biostat & Appl Math, Houston, TX 77030 USA. Harvard Univ, Sch Med, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Shen, Y (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Biostat & Appl Math, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM yshen@mdanderson.org OI Shen, Yu/0000-0002-3899-7868 FU NCI NIH HHS [R01 CA079466, U01CA-88270] NR 15 TC 15 Z9 15 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1465-4644 J9 BIOSTATISTICS JI Biostatistics PD OCT PY 2005 VL 6 IS 4 BP 604 EP 614 DI 10.1093/biostatistics/kxi030 PG 11 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 967PC UT WOS:000232102700007 PM 15860542 ER PT J AU Baldassano, CF Marangell, LB Gyulai, L Ghaemi, SN Joffe, H Kim, DR Sagduyu, K Truman, CJ Wisniewski, SR Sachs, GS Cohen, LS AF Baldassano, CF Marangell, LB Gyulai, L Ghaemi, SN Joffe, H Kim, DR Sagduyu, K Truman, CJ Wisniewski, SR Sachs, GS Cohen, LS TI Gender differences in bipolar disorder: retrospective data from the first 500 STEP-BD participants SO BIPOLAR DISORDERS LA English DT Article DE bipolar disorder; gender; gender differences; men; women ID DSM-IV; ILLNESS; PREVALENCE; WOMEN; COMORBIDITY; EPISODES; SAMPLE; PURE AB Objective: To examine gender differences in a large sample of patients with bipolar illness. Methods: Exploratory analysis of baseline data from the first 500 patients in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD), a multi-center NIMH project. Participants are allowed to have medical and psychiatric comorbidities, and to enter in any mood state, thus making the population more generalizable than many research cohorts. Diagnoses and history were assessed using structured clinical instruments administered by certified investigators. Given the exploratory nature of these analyses, there is no correction of for multiple comparisons. However, we emphasize findings that are statistically significant at the more stringent p < 0.01 level. Results: Compared with men, women had higher rates of BPII (15.3% M versus 29.0% F, p < 0.01), comorbid thyroid disease (5.7% M versus 26.9% F, p < 0.01), bulimia (1.5% M versus 11.6% F, p < .0.01) and post-traumatic stress disorder (10.6% M versus 20.9% F, p < 0.01). Women and men had equal rates of history of lifetime rapid cycling and depressive episodes. Men were more likely to have a history of legal problems (36% M versus 17.5% F, p < 0.01). Conclusions: Potentially important gender differences in certain illness characteristics were found in our study; however, in contrast to other reports, we did not find higher rates of lifetime depressive episodes or rapid cycling in women. Although our study is limited by its retrospective study design, its results are strengthened by our large sample size and use of structured interviews. C1 Univ Penn, Dept Psychiat, Bipolar Disorders Program, Philadelphia, PA 19104 USA. Baylor Coll Med, Houston, TX 77030 USA. S Cent MIRECC, Dept Vet Affairs, Houston, TX USA. Harvard Univ, Cambridge Hosp, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Dept Psychiat, Partners Bipolar Res Program, Boston, MA USA. Univ Missouri, Dept Psychiat, Kansas City, MO 64110 USA. Cornell Univ, New York Presbyterian Hosp, Weill Med Coll, Dept Psychiat, New York, NY USA. Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA 15261 USA. Harvard Univ, Massachusetts Gen Hosp, Dept Psychiat, Clin Res Program, Boston, MA USA. RP Baldassano, CF (reprint author), 3535 Mkt St,2nd Floor, Philadelphia, PA 19104 USA. EM cfb@mail.med.upenn.edu OI Wisniewski, Stephen/0000-0002-3877-9860 FU NIMH NIH HHS [N01MH80001] NR 23 TC 63 Z9 63 U1 1 U2 8 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 465 EP 470 DI 10.1111/j.1399-5618.2005.00237.x PG 6 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 965WD UT WOS:000231980700009 PM 16176440 ER PT J AU Grocela, J Mauceri, T Zietman, A AF Grocela, J Mauceri, T Zietman, A TI New life after prostate brachytherapy? Considering the fertile female partner of the brachytherapy patient SO BJU INTERNATIONAL LA English DT Article DE prostate brachytherapy; fertility; pregnancy ID IRRADIATION; MEN AB OBJECTIVES To examine several cases of unusual and unexpected pregnancy in the female partners of men treated with brachytherapy for cancer of the prostate PATIENTS AND METHODS Self-reported pregnancy of partners of patients who had had prostate brachytherapy was assessed. The dosimetry to the testicles and sperm counts were used to examine the feasibility of pregnancy in the partners. RESULTS Three reported cases of pregnancy showed the men to have viable counts of within several or all of the parameters of the World Health Organisation criteria for normal semen analysis. CONCLUSIONS These cases provide a cautionary tale and suggest that all men being treated with prostate brachytherapy should be counselled about the possibility of continued fertility. Documentation of this 'risk' on the consent form will allow for proper discussion of this issue in a clinical and medicolegal context. The key to addressing this problem is to propagate much better patient information. The topic should be addressed clearly in information booklets for the patients. Prostate brachytherapy may allow for pregnancy to be achieved in the fertile partners of patients, even after full radiation treatment of the patient. C1 Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Grocela, J (reprint author), Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. EM jgrocela@partners.org NR 5 TC 13 Z9 14 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1464-4096 J9 BJU INT JI BJU Int. PD OCT PY 2005 VL 96 IS 6 BP 781 EP 782 DI 10.1111/j.1464-410X.2005.05764.x PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 969ZL UT WOS:000232274900013 PM 16153199 ER PT J AU Nakabayashi, M Regan, MM Lifsey, D Kantoff, PW Taplin, ME Sartor, O Oh, WK AF Nakabayashi, M Regan, MM Lifsey, D Kantoff, PW Taplin, ME Sartor, O Oh, WK TI Efficacy of nilutamide as secondary hormonal therapy in androgen-independent prostate cancer SO BJU INTERNATIONAL LA English DT Article DE nilutamide; androgen-independent prostate cancer; secondary hormonal therapy; PSA response ID ANTIANDROGEN WITHDRAWAL SYNDROME; RECEPTOR GENE; MUTATIONS; PROGRESSION; CASTRATION; TRIAL AB OBJECTIVE To evaluate the activity of nilutamide as secondary hormonal therapy in patients with androgen-independent prostate cancer (AlPC), as treatment options are limited for these patients and secondary hormonal therapy with antiandrogens has advantages, including low toxicity, oral administration and high patient acceptance. PATIENTS AND METHODS We retrospectively identified 45 patients with AIPC who were treated with nilutamide as secondary hormonal therapy in two institutions. The decrease in prostate-specific antigen (PSA) levels, side-effects of treatment, and the relationship between baseline characteristics, type and duration of previous therapy and response to nilutamide were assessed. Most patients received oral nilutamide at 150 mg/day. RESULTS Eighteen of 45 evaluable patients (40%) had a PSA level decrease of >= 50%. Responders (PSA decline >= 50%) had a median (range) time to progression of 4.4 (0.31-44.7) months. There were responses to nilutamide whether used as the second to fifth line of hormonal therapy. There were no differences in response to nilutamide based on clinical stage, type of local therapy, PSA level at diagnosis or initiation of nilutamide, or type of previous antiandrogen therapy. Responders were more likely to have received monotherapy with luteinizing hormone-releasing hormone analogues or orchidectomy as first-line hormonal treatment (P = 0.02). The most common reversible adverse effects were mild to moderate visual adaptation effects, reported in 20% of patients. CONCLUSIONS Nilutamide appears to be an effective secondary hormonal therapy in patients with AIPC and is associated with a mild toxicity profile. C1 Dana Farber Canc Inst, Dept Med Oncol, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Louisiana State Univ, Sch Med, Stanley Scott Canc Ctr, Dept Hematol Oncol, New Orleans, LA USA. RP Oh, WK (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Lank Ctr Genitourinary Oncol, 44 Binney St, Boston, MA 02115 USA. EM William_oh@dfci.harvard.edu RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 NR 20 TC 20 Z9 20 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1464-4096 J9 BJU INT JI BJU Int. PD OCT PY 2005 VL 96 IS 6 BP 783 EP 786 DI 10.1111/j.1464-410X.2005.05714.x PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 969ZL UT WOS:000232274900014 PM 16153200 ER PT J AU Dole, VS Bergmeier, W Mitchell, HA Eichenberger, SC Wagner, DD AF Dole, VS Bergmeier, W Mitchell, HA Eichenberger, SC Wagner, DD TI Activated platelets induce Weibel-Palade-body secretion and leukocyte rolling in vivo: role of P-selectin SO BLOOD LA English DT Article ID VON-WILLEBRAND-FACTOR; SYSTEMIC-LUPUS-ERYTHEMATOSUS; VEIN ENDOTHELIAL-CELLS; ADHESION MOLECULES; CD40 LIGAND; RHEUMATOID-ARTHRITIS; MONOCYTE ARREST; LEUKOTRIENE A4; DEFICIENT MICE; MOUSE MODEL AB The presence of activated platelets and platelet-leukocyte aggregates in the circulation accompanies major surgical procedures and occurs in several chronic diseases. Recent findings that activated platelets contribute to the inflammatory disease atherosclerosis made us address the question whether activated platelets stimulate normal healthy endothelium. Infusion of activated platelets into young mice led to the formation of transient platelet-leukocyte aggregates and resulted in a several-fold systemic increase in leukocyte rolling 2 to 4 hours after infusion. Rolling returned to baseline levels 7 hours after infusion. Infusion of activated P-selectin(-/-) platelets did not induce leukocyte rolling, indicating that platelet P-selectin was involved in the endothelial activation. The endothelial activation did not require platelet CD40L. Leukocyte rolling was mediated solely by the interaction of endothelial P-selectin and leukocyte P-selectin glycoprotein ligand 1 (PSGL-1). Endothelial P-selectin is stored with von Willebrand factor (VWF) in Weibel-Palade bodies. The release of Weibel-Palade bodies on infusion of activated platelets was indicated by both elevation of plasma VWF levels and by an increase in the in vivo staining of endothelial P-selectin. We conclude that the presence of activated platelets in circulation promotes acute inflammation by stimulating secretion of Weibel-Palade bodies and P-selectin-mediated leukocyte rolling. C1 Ctr Blood Res, Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Wagner, DD (reprint author), Ctr Blood Res, Inst Biomed Res, 800 Huntington Ave, Boston, MA 02115 USA. EM wagner@cbr.med.harvard.edu FU NHLBI NIH HHS [HL41002, HL66105, R37 HL041002] NR 52 TC 103 Z9 108 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 1 PY 2005 VL 106 IS 7 BP 2334 EP 2339 DI 10.1182/blood-2005-04-1530 PG 6 WC Hematology SC Hematology GA 968AZ UT WOS:000232134700026 PM 15956287 ER PT J AU Stam, RW den Boer, ML Schneider, P Nollau, P Horstmann, M Beverloo, HB van der Voort, E Valsecchi, MG de Lorenzo, P Sallan, SE Armstrong, SA Pieters, R AF Stam, RW den Boer, ML Schneider, P Nollau, P Horstmann, M Beverloo, HB van der Voort, E Valsecchi, MG de Lorenzo, P Sallan, SE Armstrong, SA Pieters, R TI Targeting FLT3 in primary MLL-gene-rearranged infant acute lymphoblastic leukemia SO BLOOD LA English DT Article ID ACUTE MYELOID-LEUKEMIA; INTERNAL TANDEM DUPLICATION; TYROSINE KINASE INHIBITOR; VITRO DRUG-RESISTANCE; CELLS IN-VITRO; CLINICAL-SIGNIFICANCE; JUXTAMEMBRANE DOMAIN; ACTIVATING MUTATION; EXPRESSION; RECEPTOR AB Acute lymphoblastic leukemia (ALL) in infants is characterized by rearrangements of the mixed lineage leukemia (MLL) gene, drug resistance, and a poor treatment outcome. Therefore, novel therapeutic strategies are needed to improve prognosis. Recently, we showed that FLT3 is highly expressed in MLL rearranged ALL (MLL). Here we demonstrate FLT3 expression in infants with MILL (n = 41) to be significantly higher compared to both infant (n = 8; P <.001) and noninfant patients with ALL (n = 23; P =.001) carrying germline MLL genes. Furthermore, leukemic cells from infants with MILL were significantly more sensitive to the Fms-like tyrosine kinase 3 (FLT3) inhibitor PKC412 (N-benzoyl staurosporine) than noninfant ALL cells, and at least as sensitive as internal tandem duplication-positive (ITD+) AML cells. Surprisingly, activation loop mutations only occurred in about 3% (1 of 36) of the cases and no FLT3/ITDs were observed. However, measuring FLT3 phosphorylation in infants with MILL expressing varying levels of wild-type FLT3 revealed that high-level FLT3 expression is associated with ligand-independent FLT3 activation. This suggests that infant MLL cells displaying activated FLT3 as a result of overexpression can be targeted by FLT3 inhibitors such as PKC412. However, at concentrations of PKC412 minimally required to fully inhibit FLT3 phosphorylation, the cytotoxic effects were only fractional. Thus, PKC412-induced apoptosis in infant MLL cells is unlikely to be a consequence of FLT3 inhibition alone but may involve inhibition of multiple other kinases by this drug. C1 Erasmus Med Ctr, Sophia Childrens Hosp, Dept Pediat Oncol Hematol, NL-3000 CB Rotterdam, Netherlands. Univ Hamburg, Hosp Eppendorf, Inst Clin Chem, D-20246 Hamburg, Germany. Univ Hamburg, Hosp Eppendorf, Clin Pediat Hematol & Oncol, D-20246 Hamburg, Germany. Erasmus MC, Dept Clin Genet, Rotterdam, Netherlands. Univ Milano Bicocca, Dept Clin Med Prevent & Biotechnol, Sect Med Stat, Monza, Italy. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Childrens Hosp, Div Pediat Hematol Oncol, Boston, MA 02115 USA. RP den Boer, ML (reprint author), Erasmus Med Ctr, Sophia Childrens Hosp, Dept Pediat Oncol Hematol, Rm Sp 2456,Dr Molewaterpl 60,POB 2060, NL-3000 CB Rotterdam, Netherlands. EM m.l.denboer@erasmusmc.nl NR 47 TC 88 Z9 90 U1 0 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 2484 EP 2490 DI 10.1182/blood-2004-09-3667 PG 7 WC Hematology SC Hematology GA 968AZ UT WOS:000232134700045 PM 15956279 ER PT J AU Cho, JH Fraser, IP Fukase, K Kusumoto, S Fujimoto, Y Stahl, GL Ezekowitz, RAB AF Cho, JH Fraser, IP Fukase, K Kusumoto, S Fujimoto, Y Stahl, GL Ezekowitz, RAB TI Human peptidoglycan recognition protein S is an effector of neutrophil-mediated innate immunity SO BLOOD LA English DT Article ID GRAM-NEGATIVE BACTERIA; L-ALANINE AMIDASE; ESCHERICHIA-COLI; DROSOPHILA-MELANOGASTER; POSITIVE BACTERIA; BOMBYX-MORI; BINDING; LYSOZYME; GENE; ACTIVATION AB Innate immune responses to bacteria re quire cooperative interactions between host recognition molecules and phagocytes. The peptidoglycan recognition proteins (PGRPs) are a large group of proteins found in insects and mammals that bind to bacterial peptidoglycan (PGN): PGRP-S is located with other antimicrobial proteins, such as lysozyme, in the granules of human neutrophils. Whereas both PGRP-S and. lysozyme recognize PGN, the exact binding specificity of human PGRP-S, its functional activity, and its potential synergy with other neutrophil-derived bactericidal proteins such as lysozyme have not been determined. Herd we show that human PGRP-S binds to and inhibits the growth of Staphylococcus aureus (containing lysine-type PGN) and Escherichia coli (containing mesodiaminopimelic acid-type PGN). The binding, affinity and thus antimicrobial activity of. PGRP-S is determined by the third amino acid in, the PGN stem peptide. Furthermore, the antimicrobial effect of PGRP-S against E coli is synergistic with lysozyme, and lysozyme and PGRP-S colocalize in neutrophil extracellular traps (NETs), suggesting that these granule-derived proteins act together to kill bacteria trapped in the NETs. Taken together, these results indicate that human PG. RP-S; plays a role in innate immunity in the context of neutrophils by contributing to the killing of intracellular and extracellular bacteria. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat,Lab Dev Immunol, Boston, MA 02114 USA. Osaka Univ, Grad Sch Sci, Dept Chem, Osaka, Japan. Harvard Univ, Brigham & Womens Hosp, Sch Med,Ctr Expt Therapeut & Reperfus Injury, Dept Anesthesiol Perioperat & Pain Med, Boston, MA 02115 USA. RP Ezekowitz, RAB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat,Lab Dev Immunol, GRJ 1402,55 Fruit St, Boston, MA 02114 USA. EM ezekowitz.alan@mgh.harvard.edu RI Fujimoto, Yukari/M-7282-2014 OI Fujimoto, Yukari/0000-0001-5320-3192 FU NIAID NIH HHS [P01 AI 44220] NR 42 TC 74 Z9 78 U1 1 U2 10 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 1 PY 2005 VL 106 IS 7 BP 2551 EP 2558 DI 10.1182/blood-2005-02-0530 PG 8 WC Hematology SC Hematology GA 968AZ UT WOS:000232134700055 PM 15956276 ER PT J AU Lippert, B Berger, K Berntorp, E Giangrande, P van den Berg, M Schramm, W Siebert, U AF Lippert, B Berger, K Berntorp, E Giangrande, P van den Berg, M Schramm, W Siebert, U CA European Haemophilia Economic Stud TI Cost effectiveness of haemophilia treatment: a cross-national assessment SO BLOOD COAGULATION & FIBRINOLYSIS LA English DT Article DE cost-effectiveness analysis; SF-6D; quality of life; haemophilia care; prophylaxis; on-demand therapy ID QUALITY-OF-LIFE; HIV-POSITIVE PATIENTS; PROPHYLACTIC TREATMENT; ON-DEMAND; RESOURCE UTILIZATION; ORTHOPEDIC STATUS; YOUNG-PATIENTS; CHILDREN; HEALTH; THERAPY AB The aim of this study was to assess the incremental cost effectiveness of on-demand versus prophylactic haemophilia therapy in Germany, Sweden, the United Kingdom and The Netherlands from the third-party payers' perspective. Using a decision tree model, the cost effectiveness of on-demand versus prophylactic therapy was analysed by extrapolating data from the European Haemophilia Economic Study to a 1-year analytic time horizon. Five hundred and six patients with severe haemophilia A and B, without inhibitors and at least 14 years of age, were enrolled in this study. Patients treated prophylactically had fewer bleeds than patients treated on-demand. With prophylactic treatment, the incremental cost per avoided bleeding ranged from EURO6650 for patients 30 years of age or younger in Germany to EURO14 140 for patients over 30 years old in Sweden. If quality of life was taken into account, patients receiving prophylactic treatment had higher mean utilities than patients on on-demand therapy. The incremental effectiveness ratios in Germany were EURO1.2 million per quality-adjusted life year gained for patients 30 years or younger and HIV-positive and EURO2.2 million for patients 30 years or younger and HIV-negative. In the group aged over 30 years and HIV-positive the on-demand treatment strategy was dominant, whereas in the over 30 years/HIV-negative group the incremental cost-utility ratio was EURO4.7 million per quality-adjusted life year. Based on our decision analysis, the use of prophylactic treatment was overall more effective than on-demand therapy in young haemophiliacs, but at extremely high cost. C1 Univ Hosp Munich, Dept Haemostasis & Transfus Med, Munich, Germany. Univ Munich, Inst Med Informat Biostat & Epidemiol, Program Hlth Technol Assessment & Decis Sci, Munich, Germany. Lund Univ, Malmo Univ Hosp, Dept Coagulat Disorders, Lund, Sweden. Churchill Hosp, Oxford Haemophilla Ctr, Oxford OX3 7LJ, England. Univ Med Ctr, Dept Paediat, Utrecht, Netherlands. Univ Hlth Sci Med Informat & Technol, Hall in Tirol, Austria. Dept Publ Hlth Decis Making & Hlth Technol Assess, Hall in Tirol, Austria. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA USA. RP Siebert, U (reprint author), Harvard Univ, Inst Technol Assessment, Massachusetts Gen Hosp, Sch Med, 101 Merrimac St,10th Floor, Boston, MA 02114 USA. EM uwe@mgh-ita.org NR 36 TC 24 Z9 24 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0957-5235 J9 BLOOD COAGUL FIBRIN JI Blood Coagul. Fibrinolysis PD OCT PY 2005 VL 16 IS 7 BP 477 EP 485 DI 10.1097/01.mbc.0000178830.39526.ff PG 9 WC Hematology SC Hematology GA 977FV UT WOS:000232789300004 PM 16175006 ER PT J AU Caplan, D Chen, E Waters, G Robakis, D AF Caplan, D Chen, E Waters, G Robakis, D TI Syntactic and semantic influences on BOLD signal responses to comprehension of relative clauses SO BRAIN AND LANGUAGE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Neuropsychol Lab, Boston, MA 02114 USA. Boston Univ, Sargent Coll Allied Hlth Profess, Dept Hlth Sci, Boston, MA 02215 USA. EM dcaplan@partners.org NR 3 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0093-934X J9 BRAIN LANG JI Brain Lang. PD OCT PY 2005 VL 95 IS 1 BP 72 EP 73 DI 10.1016/j.bandl.2005.07.040 PG 2 WC Audiology & Speech-Language Pathology; Linguistics; Neurosciences; Psychology, Experimental SC Audiology & Speech-Language Pathology; Linguistics; Neurosciences & Neurology; Psychology GA 975HF UT WOS:000232650900034 ER PT J AU Sullivan, T Raad, RA Goldberg, S Assaad, SI Gadd, M Smith, BL Powell, SN Taghian, AG AF Sullivan, T Raad, RA Goldberg, S Assaad, SI Gadd, M Smith, BL Powell, SN Taghian, AG TI Tubular carcinoma of the breast: a retrospective analysis and review of the literature SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE breast cancer; elderly; local failure; radiation therapy; tubular ID RANDOMIZED CLINICAL-TRIAL; CONSERVATIVE SURGERY; LOCAL RECURRENCE; RISK-FACTORS; FOLLOW-UP; CANCER; THERAPY; WOMEN; IRRADIATION; LUMPECTOMY AB Background. The favorable prognosis associated with tubular carcinoma of the breast has led some studies to propose less aggressive treatments for patients with this disease. This study aims to address the extent of therapy needed for tubular patients. Methods. A retrospective review identified 73 cases of tubular carcinoma treated at the Massachusetts General Hospital between 1980 and 2002. Primary treatment was conservative surgery (CS) plus radiation therapy (RT) in 67%, CS without RT in 18%, and mastectomy in 15%. Median follow-up time was 90.5 months. The published literature of 529 conservatively treated tubular carcinomas was reviewed along with the 62 conservative cases from this series. Results. No patients developed distant metastasis or died from this disease. Local failure occurred in three (4%) of the cases, after 13, 84 and 121 months. All three had initially been treated with CS + RT. Five cases were node-positive, three of which were associated with a primary tumor smaller than 1 cm. Thirteen women, with a median age of 74, were treated by CS without RT and none recurred. A literature review showed that adjuvant RT reduces local failure following CS for tubular carcinoma. Conclusions. Tubular carcinoma is associated with an excellent prognosis, but long-term follow-up is essential for detecting local failures and a small primary tumor size does not preclude nodal involvement. Adjuvant RT reduces the incidence of local failure following CS for tubular carcinoma, however, elderly women treated by CS may have a very low risk of local recurrence without adjuvant RT. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Canc Ctr, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med,Canc Ctr, Dept Surg Oncol, Boston, MA 02114 USA. RP Taghian, AG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Canc Ctr, Dept Radiat Oncol, Cox 3,100 Blossom St, Boston, MA 02114 USA. EM ataghian@partners.org NR 45 TC 18 Z9 22 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD OCT PY 2005 VL 93 IS 3 BP 199 EP 205 DI 10.1007/s10549-005-5089-7 PG 7 WC Oncology SC Oncology GA 974WG UT WOS:000232621500003 PM 16142444 ER PT J AU Zangari, M Esseltine, D Lee, CK Barlogie, B Elice, F Burns, MJ Kang, SH Yaccoby, S Najarian, K Richardson, P Sonneveld, P Tricot, G AF Zangari, M Esseltine, D Lee, CK Barlogie, B Elice, F Burns, MJ Kang, SH Yaccoby, S Najarian, K Richardson, P Sonneveld, P Tricot, G TI Response to bortezomib is associated to osteoblastic activation in patients with multiple myeloma SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE myeloma; bortezomib; osteoblast; bone; intact parathyroid hormone AB The prompt response to bortezomib observed in a 63-year-old woman with multiple myeloma was associated with a significant increase in alkaline phosphatase (ALP). After similar elevations were noted in patients responding to bortezomib, thalidomide, dexamethasone combination, ALP levels were analysed in two large bortezomib trials. A statistically significant elevation of ALP from baseline was observed in responding patients (complete and partial responders) within three cycles of therapy. The rise in ALP after bortezomib in three patients was explained by a parallel increase in bone-specific ALP and parathyroid hormone, suggesting that response to bortezomib in myeloma is closely associated with osteoblastic activation. C1 Univ Arkansas Med Sci, Myeloma Inst Res & Therapy, Little Rock, AR 72205 USA. Millennium Pharmaceut Co, Cambridge, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Rotterdam Hosp, Dept Hematol, Rotterdam, Netherlands. RP Zangari, M (reprint author), Univ Arkansas Med Sci, Myeloma Inst Res & Therapy, 4301 W Markham St Slot 776, Little Rock, AR 72205 USA. EM zangarimaurizio@uams.edu NR 10 TC 124 Z9 125 U1 0 U2 1 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 71 EP 73 DI 10.1111/j.1365-2141.2005.05733.x PG 3 WC Hematology SC Hematology GA 965WE UT WOS:000231980800010 PM 16173965 ER PT J AU Li, AH Goldwasser, MA Zhou, JB Armstrong, SA Wang, H Dalton, V Fletcher, JA Sallan, SE Silverman, LB Gribben, JG AF Li, AH Goldwasser, MA Zhou, JB Armstrong, SA Wang, H Dalton, V Fletcher, JA Sallan, SE Silverman, LB Gribben, JG TI Distinctive IGH gene segment usage and minimal residual disease detection in infant acute lymphoblastic leukaemias SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE infant leukaemia; acute lymphoblastic leukaemia; minimal residual disease; mixed-lineage leukaemia; immunoglobulin heavy chain genes ID CHAIN CDR3 REGIONS; PRE-B CELLS; IMMUNOGLOBULIN; REARRANGEMENTS; CHILDHOOD; CHILDREN; EXPRESSION; DIVERSITY; LINEAGE; RECOMBINATION AB Infant acute lymphoblastic leukaemia (ALL) represents a rare but unique subset with poor prognosis. We analysed mixed-lineage leukaemia (MLL) gene rearrangements and the sequences of complete and incomplete immunoglobulin heavy chain gene rearrangements (IGH) in 14 infants (age <= 12 months at diagnosis) enrolled on Dana-Farber Cancer Institute ALL Consortium Protocol 95-01. The dynamics of the leukaemic clone were followed during the course of the disease by quantitative real-time polymerase chain reaction of IGH rearrangements. Sixteen sequences were obtained from 13 (93%) of these infants. There was marked over usage of the V(H)6.1 gene segment (64%) in infants compared with older children with ALL (8%), (P < 0.001) and overusage of D(H)6 (P = 0.004) and J(H)1 (P = 0.004). Poor outcome was associated with MLL gene rearrangements rather than any specific V(H)D(H)J(H) gene usage patterns. Levels of minimal residual disease (MRD) at the end of induction appeared to be high in infants with ALL compared with older children, and although the number of infant cases studied was small, there were no differences in MRD levels after induction therapy in infant ALL with or without MLL gene rearrangements (P = 0.41) and quantitative MRD assessment at the early time points may not be predictive of outcome. Novel treatment strategies are required to improve the outcome in this poor prognosis subset of children with ALL. C1 Umea Univ, Dept Med Biosci, Umea, Sweden. Dana Farber Canc Inst, Div Biostat & Computat Biol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Sch Med, Dept Med,Div Haematol Oncol, Boston, MA 02115 USA. RP Gribben, JG (reprint author), Barts & London Sch med, Dept Med Oncol, Charterhouse Sq, London EC1M 6BQ, England. EM john.gribben@cancer.org.uk FU NCI NIH HHS [P01 CA68484] NR 41 TC 6 Z9 6 U1 0 U2 0 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 2 BP 185 EP 192 DI 10.1111/j.1365-2141.2005.05754.x PG 8 WC Hematology SC Hematology GA 969NL UT WOS:000232240800006 PM 16197448 ER PT J AU Wolanskyj, AP Lasho, TL Schwager, SM McClure, RF Wadleigh, M Lee, SJ Gilliland, DG Tefferi, A AF Wolanskyj, AP Lasho, TL Schwager, SM McClure, RF Wadleigh, M Lee, SJ Gilliland, DG Tefferi, A TI JAK2(V617F) mutation in essential thrombocythaemia: clinical associations and long-term prognostic relevance SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE JAK2 mutation; essential thrombocythaemia; myeloproliferative disorders; prognosis ID CHRONIC MYELOPROLIFERATIVE DISORDERS; TYROSINE KINASE JAK2; POLYCYTHEMIA-VERA; MYELOID METAPLASIA; DIAGNOSTIC-VALUE; CLONAL DISORDER; EXPRESSION; MYELOFIBROSIS; MEGAKARYOCYTE; COMPLICATIONS AB Clinical correlates and long-term prognostic relevance of the JAK2(V617F) mutation was studied in 150 patients with essential thrombocythaemia (ET) from a single institution and followed for a median of 11.4 years. During this period, thrombotic complications were documented in 62 patients (41.3%) and transformation into acute myeloid leukaemia (AML), polycythaemia vera (PV), or myelofibrosis with myeloid metaplasia (MMM) occurred in 4 (2.7%), 8 (5.3%), and 15 (10%) patients, respectively. JAK2(V617F) was detected in either archived bone marrow or blood cells from 73 patients (48.7%) but none were homozygous for the mutant allele. Parameters at diagnosis that were significantly associated with the presence of JAK2(V617F) included advanced age and higher counts of both haemoglobin and leucocytes. During follow-up, patients with the mutation were more likely to transform into PV but the incidences of AML, MMM, or thrombotic events were similar between patients with and without the mutation. Multivariate analysis identified advanced age, higher haemoglobin level, and thrombosis history but not the presence of JAK2(V617F) as independent predictors of inferior survival. Therefore, although the presence of JAK2(V617F) in ET appears to promote a PV phenotype, it might not carry treatment-relevant information. C1 Mayo Clin & Mayo Fdn, Div Hematol, Rochester, MN 55905 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Tefferi, A (reprint author), Mayo Clin & Mayo Fdn, Div Hematol, 200 1st St SW, Rochester, MN 55905 USA. EM tefferi.ayalew@mayo.edu NR 30 TC 207 Z9 225 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 2 BP 208 EP 213 DI 10.1111/j.1365-2141.2005.05764.x PG 6 WC Hematology SC Hematology GA 969NL UT WOS:000232240800009 PM 16197451 ER PT J AU Huynh, N Dolan, B Lee, S Whitcher, JP Stanley, J Whitcher, JP Lee, S AF Huynh, N Dolan, B Lee, S Whitcher, JP Stanley, J Whitcher, JP Lee, S TI Management of phaeniciatic ophthalmomyiasis externa SO BRITISH JOURNAL OF OPHTHALMOLOGY LA English DT Article C1 Univ Calif San Francisco, Dept Ophthalmol, San Francisco, CA 94122 USA. San Francisco VA Med Ctr, San Francisco, CA USA. RP Lee, S (reprint author), Univ Calif San Francisco, Dept Ophthalmol, San Francisco, CA 94122 USA. EM selee@itsa.ucsf.edu NR 4 TC 2 Z9 4 U1 0 U2 0 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0007-1161 J9 BRIT J OPHTHALMOL JI Br. J. Ophthalmol. PD OCT PY 2005 VL 89 IS 10 BP 1377 EP 1378 DI 10.1136/bjo.2005.071597 PG 2 WC Ophthalmology SC Ophthalmology GA 965UD UT WOS:000231974900040 PM 16170142 ER PT J AU Lee, MS Lessell, S AF Lee, MS Lessell, S TI Choroidal neovascularisation associated with meningioma SO BRITISH JOURNAL OF OPHTHALMOLOGY LA English DT Article ID OPTIC-NERVE C1 Cleveland Clin Fdn, Cole Eye Inst, Cleveland, OH 44195 USA. Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Neuroophthalmol Unit, Boston, MA 02114 USA. RP Lee, MS (reprint author), Cleveland Clin Fdn, Cole Eye Inst I32, 9500 Euclid Ave, Cleveland, OH 44195 USA. EM leem4@ccf.org NR 10 TC 0 Z9 0 U1 0 U2 1 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0007-1161 J9 BRIT J OPHTHALMOL JI Br. J. Ophthalmol. PD OCT PY 2005 VL 89 IS 10 BP 1384 EP 1386 DI 10.1136/bjo.2005.071696 PG 3 WC Ophthalmology SC Ophthalmology GA 965UD UT WOS:000231974900048 PM 16170150 ER PT J AU Braunwald, E AF Braunwald, E TI Cardiology: How did we get here, where are we today and where are we going? SO CANADIAN JOURNAL OF CARDIOLOGY LA English DT Article; Proceedings Paper CT 58th Annual Meeting of the Canadian-Cardiovascular-Society CY OCT 23, 2005 CL Montreal, CANADA SP Canadian Cardiovasc Soc, Pulsus Grp Inc C1 Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Braunwald, E (reprint author), TIMI Study Grp, 350 Longwood Ave,1st Off Floor, Boston, MA 02115 USA. EM ebraunwald@partners.org NR 0 TC 3 Z9 3 U1 0 U2 0 PU PULSUS GROUP INC PI OAKVILLE PA 2902 S SHERIDAN WAY, OAKVILLE, ONTARIO L6J 7L6, CANADA SN 0828-282X J9 CAN J CARDIOL JI Can. J. Cardiol. PD OCT PY 2005 VL 21 IS 12 BP 1015 EP 1017 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 978KC UT WOS:000232871000004 PM 16234882 ER PT J AU Copeland, LA Elshaikh, MA Jackson, J Penner, LA Underwood, W AF Copeland, LA Elshaikh, MA Jackson, J Penner, LA Underwood, W TI Impact of brachytherapy on regional, racial, marital status, and age-related patterns of definitive treatment for clinically localized prostate carcinoma SO CANCER LA English DT Article DE permanent prostate brachytherapy; radical prostatectomy; external-beam radiation therapy; prostate carcinoma ID DATA-BASE REPORT; RADIATION-THERAPY; BEAM RADIATION; CANCER; PREFERENCES; MORBIDITY; ROBOTICS; OUTCOMES; MEN; US AB BACKGROUND. The impact of the increased use of permanent prostate brachy-therapy compared with other treatment modalities (such as radical prostatectomy and external-beam radiation therapy [EBRT]) for the treatment of clinically localized prostate carcinoma, and the previously reported regional, racial, and age-related variations in prostate carcinoma treatment, have not been well characterized to date. Therefore, the authors evaluated the impact of permanent prostate brachytherapy on the relative rates of the use of specific prostate carcinoma treatment modalities over time. METHODS. Surveillance, Epidemiology, and End Results (SEER) cancer registry data from 1995 to 2000 were analyzed in a longitudinal, observational study utilizing bivariate and multivariate techniques. RESULTS. Differential changes in the use of specific definitive treatment modalities were noted by region, age group, racial/ethnic group, and marital status. Increasing use of permanent prostate brachytherapy, with and without concomitant EBRT, was proportional to the decreasing use of radical prostatectomy alone and EBRT alone over time. CONCLUSIONS. The current study revealed that permanent prostate brachytherapy appears to be replacing other treatment modalities in increasing numbers of clinically localized prostate carcinoma cases. Persistent regional, racial/ethnic, marital status, and age-related differences in the use of permanent prostate brachytherapy merit further investigation. C1 Univ Michigan, Urol Ctr, Dept Urol, Div Clin Res & Qual Assurance, Ann Arbor, MI 48109 USA. Vet Affairs Ctr Practice Management & Outcomes Re, Ann Arbor, MI USA. Wayne State Univ, Dept Family Med, Detroit, MI USA. Wayne State Univ, Karmanos Canc Inst, Commun & Behav Oncol Program, Detroit, MI USA. Univ Michigan, Ctr African Amer & African Studies, Ann Arbor, MI 48109 USA. Univ Michigan, Inst Social Res, Res Ctr Grp Dynam, Ann Arbor, MI 48109 USA. Vet Affairs Med Ctr, Dept Radiat Oncol, Ann Arbor, MI USA. Univ Michigan, Dept Radiat Oncol, Ann Arbor, MI 48109 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, Dept Psychiat, San Antonio, TX USA. RP Underwood, W (reprint author), Univ Michigan, Urol Ctr, Dept Urol, Div Clin Res & Qual Assurance, TC 3746,POB 0330,1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. EM wunderwo@umich.edu OI Copeland, Laurel/0000-0002-9478-0209 NR 25 TC 8 Z9 8 U1 0 U2 1 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 1372 EP 1380 DI 10.1002/cncr.21341 PG 9 WC Oncology SC Oncology GA 966EA UT WOS:000232001200006 PM 16118801 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 McDonald, JM See, SJ Tremont, IW Colman, H Gilbert, MR Groves, M Burger, PC Louis, DN Giannini, C Fuller, G Passe, S Blair, H Jenkins, RB Yang, H Ledoux, A Aaron, J Tipnis, U Zhang, W Hess, K Aldape, K AF McDonald, JM See, SJ Tremont, IW Colman, H Gilbert, MR Groves, M Burger, PC Louis, DN Giannini, C Fuller, G Passe, S Blair, H Jenkins, RB Yang, H Ledoux, A Aaron, J Tipnis, U Zhang, W Hess, K Aldape, K TI The prognostic impact of histology and 1p/19q status in anaplastic oligodendroglial tumors SO CANCER LA English DT Article DE oligodendroglioma; monomorphic pattern; nonrandom allelic loss; 1p/19q status; survival ID MOLECULAR-GENETIC ANALYSIS; GROWTH-FACTOR RECEPTOR; ARMS 1P; 19Q; CANCER; GRADE; 10Q; OLIGOASTROCYTOMAS; CHEMOTHERAPY; SIGNATURE AB BACKGROUND. it has been reported previously that the combined loss of chromosomal arms 1p and 19q is a significant predictor of outcome for patients with anaplastic oligodendroglial (A0) tumors and that such chromosomal loss correlates with classic histology in A0. The authors sought to determine whether histology was an equivalent or superior predictor of outcome compared with 1p/19q status in 131 patients with A0 tumors. METHODS. The status of 1p and 19q was determined using real-time, quantitative polymerase chain reaction analysis and/or fluorescence in situ hybridization. Clinical features (response to adjuvant therapy and tumor location) and molecular genetic abnormalities (9p and 10q deletions, overexpression of p53 and epidermal growth factor receptor) were determined on available specimens. Histologic assessments for classic oligodendroglial features were performed by five neuropathologists. RESULTS. Classic histology was associated closely with 1p/19q loss, as reported previously. Patients who had tumors that were considered classic by at least four of the five neuropathologists showed significantly increased progression-free and overall survival compared with the patients who had less classic tumors. The authors also tested the correlation between 1p/19q status and outcome in subsets of patients stratified according to classic tumor features. The association of 1p/19q status with survival was related closely to the presence of classic histology. Loss of 1p/19q was predictive of improved outcome only among patients who had tumors with classic histologic features. CONCLUSIONS. The current results suggested that, in addition to 1p/19q status, histologic features contribute information to the prediction of outcome in patients with A0. Loss of 1p and 19q appeared to be a prognostic marker only in the subset of patients who had AO tumors with classic histologic features. C1 Univ Texas, MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA. Johns Hopkins Univ, Sch Med, Dept Pathol, Div Neuropathol, Baltimore, MD USA. Massachusetts Gen Hosp, Mol Neurooncol Lab, Boston, MA 02114 USA. Massachusetts Gen Hosp, Mol Pathol Unit, Dept Pathol, Ctr Canc, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neurosurg Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Mayo Clin & Mayo Fdn, Dept Pathol, Rochester, MN 55905 USA. Mayo Clin & Mayo Fdn, Div Lab Genet, Rochester, MN 55905 USA. Univ Texas, MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA. RP Aldape, K (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Pathol, POB 85,1515 Holcombe Blvd, Houston, TX 77030 USA. EM kaldape@mdanderson.org RI Gilbert, Mark/J-7494-2016; OI Gilbert, Mark/0000-0003-2556-9722; Fuller, Gregory/0000-0001-9447-2647 FU NCI NIH HHS [CA57683, P01 CA85799] NR 31 TC 84 Z9 85 U1 0 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD OCT 1 PY 2005 VL 104 IS 7 BP 1468 EP 1477 DI 10.1002/cncr.21338 PG 10 WC Oncology SC Oncology GA 966EA UT WOS:000232001200017 PM 16088966 ER PT J AU Thurston, SW Liu, G Miller, DP Christiani, DC AF Thurston, SW Liu, G Miller, DP Christiani, DC TI Modeling lung cancer risk in case-control studies using a new dose metric of smoking SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article; Proceedings Paper CT 95th Annual Meeting of the American-Association-for-Cancer-Research CY MAR 27-31, 2004 CL Orlando, FL SP Amer Assoc Canc Res ID CUMULATIVE CIGARETTE-SMOKING; MICROSOMAL EPOXIDE HYDROLASE; MULTISTAGE MODEL; DNA-DAMAGE; EARLY AGE; CARCINOGENESIS; EXPOSURE; POLYMORPHISMS; EPIDEMIOLOGY; PREVENTION AB Many approaches have been taken to adjust for smoking in modeling cancer risk. In case-control studies, these metrics are often used arbitrarily rather than being based on the properties of the metric in the context of the study. Depending on the underlying study design, hypotheses, and base population, different metrics may be deemed most appropriate. We present our approach to evaluating different smoking metrics. We examine the properties of a new metric, "logcig-years", that we initially derived from using a biological model of DNA adduct formation. We compare this metric to three other smoking metrics, namely pack-years, square-root pack-years, and a model in which smoking duration and intensity are separate variables. Our comparisons use generalized additive models and logistic regression to examine the relationship between the logit probability of cancer and each of the metrics, adjusting for other covariates. All models were fit using data from a lung cancer study of 1,275 cases and 1,269 controls that has focused on gene-smoking relationships. There was a very significant, linear relationship between logcig-years and the logit probability of lung cancer in this sample, without any need to adjust for smoking status. These properties together were not shared by the other metrics. In this sample, logcig-years captured more information about smoking that is important in lung cancer risk than the other metrics. In conclusion, we provide a general framework for evaluating different smoking metrics in studies where smoking is a critical variable. C1 Univ Rochester, Dept Biostat & Computat Biol, Rochester, NY 14642 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Occupat Hlth Program, Cambridge, MA 02138 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. RP Thurston, SW (reprint author), Univ Rochester, Dept Biostat & Computat Biol, 601 Elmwood Ave,Box 630, Rochester, NY 14642 USA. EM thurston@bst.rochester.edu RI Liu, Geoffrey/N-4421-2016 FU NCI NIH HHS [R01 CA092824, CA74386, CA092824, R01 CA074386, P50 CA090578, P20 CA090578, CA90578]; NIEHS NIH HHS [K22 ES11027, K22 ES011027] NR 40 TC 28 Z9 28 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD OCT PY 2005 VL 14 IS 10 BP 2296 EP 2302 DI 10.1158/1055-9965.EPI-04-0393 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 972SL UT WOS:000232473400004 PM 16214908 ER PT J AU Zhou, W Suk, R Liu, G Park, S Neuberg, DS Wain, JC Lynch, TJ Giovannucci, E Christiani, DC AF Zhou, W Suk, R Liu, G Park, S Neuberg, DS Wain, JC Lynch, TJ Giovannucci, E Christiani, DC TI Vitamin D is associated with improved survival in early-stage non-small cell lung cancer patients SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID FOOD FREQUENCY QUESTIONNAIRE; MALE HEALTH-PROFESSIONALS; PROSTATE-CANCER; E-CADHERIN; ULTRAVIOLET-RADIATION; BREAST-CANCER; UNITED-STATES; BETA-CATENIN; ALL-TRANS; MORTALITY AB Vitamin D may inhibit the development and progression of a wide spectrum of cancers. We investigated the associations of surgery season and vitamin D intake with recurrence-free survival (RFS) and overall survival in 456 early-stage non-small cell lung cancer patients. The data were analyzed using log-rank test and Cox proportional hazards models. The median (range) follow-up time was 71 (0.1-140) months, with 161 recurrence and 231 deaths. Patients who had surgery in summer had a better RFS than those who had surgery in winter (adjusted hazard ratio, 0.75; 95% confidence interval, 0.56-1.01), with 5-year RFS rates of 53% (45-61%) and 40% (32-49%), respectively (P = 0.10, log-rank test). Similar association between surgery season and RFS was found among the 321 patients with dietary information (P = 0.33, log-rank test). There was no statistically significant association between vitamin D intake and RFS. Because both season and vitamin D intake are important predictors for vitamin D levels, we investigated the joint effects of surgery season and vitamin D intake. Patients who had surgery during summer with the highest vitamin D intake had better RFS (adjusted hazard ratio, 0.33; 95% confidence interval, 0.15-0.74) than patients who had surgery during winter with the lowest vitamin D intake, with the 5-year RFS rates of 56% (34-78%) and 23% (4-42%), respectively. Similar associations of surgery season and vitamin D intake with overall survival were also observed. In conclusion, the joint effects of surgery season and recent vitamin D intake seem to be associated with the survival of early-stage non-small cell lung cancer patients. C1 Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Occupat Hlth Program, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Cambridge, MA 02138 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Thorac Surg Unit, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Publ Hlth, Channing Lab, Boston, MA 02115 USA. RP Christiani, DC (reprint author), Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Occupat Hlth Program, 665 Huntington Ave, Boston, MA 02115 USA. EM dchris@hohp.harvard.edu RI Liu, Geoffrey/N-4421-2016 FU NCI NIH HHS [CA 074386, CA 090578, 5T32 CA 071345-08, CA 092824]; NIEHS NIH HHS [ES/CA 06409, ES 00002] NR 30 TC 82 Z9 88 U1 0 U2 10 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 2303 EP 2309 DI 10.1158/1055-9965.EPI-05-0335 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 972SL UT WOS:000232473400005 PM 16214909 ER PT J AU Chen, WY Bertone-Johnson, ER Hunter, DJ Willett, WC Hankinson, SE AF Chen, WY Bertone-Johnson, ER Hunter, DJ Willett, WC Hankinson, SE TI Associations between Polymorphisms in the vitamin D receptor and breast cancer risk SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID BONE-MINERAL DENSITY; START CODON POLYMORPHISM; TRANSLATION INITIATION SITE; GENE POLYMORPHISMS; POSTMENOPAUSAL WOMEN; CELL-PROLIFERATION; FOKI; 1,25-DIHYDROXYVITAMIN-D; 25-HYDROXYVITAMIN-D; FRACTURES AB Biological and epidemiologic data suggest that vitamin D levels may influence breast cancer development. The vitamin D receptor (VDR) is a crucial mediator for the cellular effects of vitamin D and additionally interacts with other cell-signaling pathways that influence cancer development. Because functional data exist on FOK1 and previous studies have suggested a relation between BSM1 and breast cancer risk, we evaluated the associations of the FOK1 and BSM1 VDR polymorphisms and breast cancer risk. In a case-control study nested within the Nurses' Health Study, we genotyped 1,234 incident cases (diagnosed between return of a blood sample in 1989-1990 and June 1, 2000) and 1,676 controls for FOK1, and 1,180 cases and 1,547 controls for BSM1. We observed a significantly increased risk of breast cancer among carriers of the ff genotype of FOK1 (multivariate odds ratio, 1.34; 95% confidence intervals, 1.06-1.69) compared with those with FF. We did not observe an association between polymorphisms in BSM1 and breast cancer risk (multivariate odds ratio, 0.93; 95% confidence intervals, 0.72-1.20) for BB versus bb). The FOK1 association did not vary significantly by menopausal status, estrogen, and progesterone receptor status of the tumors, or plasma levels of 25 hydroxyvitamin D or 1,25 dihydroxyvitamin D. Our results suggest that the VDR may be a mediator of breast cancer risk and could represent a target for cancer prevention efforts. C1 Harvard Univ, Brigham & Womens Hosp, Sch Publ Hlth, Dept Med,Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Univ Massachusetts, Dept Publ Hlth, Amherst, MA 01003 USA. RP Chen, WY (reprint author), Harvard Univ, Sch Med, Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA. EM wendy.chen@achaming.hardvard.edu FU NCI NIH HHS [CA87969, CA49449] NR 36 TC 80 Z9 85 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 2335 EP 2339 DI 10.1158/1055-9965.EPI-05-0283 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 972SL UT WOS:000232473400009 PM 16214913 ER PT J AU Jiang, W Xu, CJ Shao, ZM Zhou, WJ Ye, B Tian, PK Zhu, JD Gu, JR AF Jiang, W Xu, CJ Shao, ZM Zhou, WJ Ye, B Tian, PK Zhu, JD Gu, JR TI Enhanced efficiency and specificity of ovarian cancer gene therapy in rats with a novel nonviral gene delivery system (GE7) via intraovarian artery perfusion approach SO CANCER GENE THERAPY LA English DT Article DE gene therapy; HSV1-tk; GE7 delivery system; rats; intra-artery ID THYMIDINE KINASE GENE; BREAST-CANCER; SUICIDE; EXPRESSION; CELLS; CARCINOMA; PROMOTER; ADENOCARCINOMA; GANCICLOVIR; INJECTION AB Transfer of the herpes simplex virus type 1-thymidine kinase gene, followed by the administration of ganciclovir ( HSV1-tk/GCV) into ovarian cancer-derived cell line either in vitro or transplanted into nude mice has been shown to provide a potential strategy for the gene therapy of ovarian cancer. We investigated the antitumor effects of HSV1-tk/ GCV strategy with a chemically induced rat ovarian cancer model and a tumor-selective gene delivery by a novel nonviral gene delivery system (GE7) through the ovarian artery and tail vein. We demonstrated the expression of a reporter gene, beta-gal gene, as well as HSV1-tk gene in tumors and other organs, evaluated the overall antitumor effects after the GCV treatment and analyzed the tumor cell cycle phase distribution. Via the ovarian artery route, the expressions of beta-gal and HSV1-tk in tumors were significantly stronger than those expressed in such organs as the hearts, livers, spleens, lungs and kidneys. However, no beta-gal and HSV1-tk were detected in the tumor tissues when administrated via the tail vein, and little was found in other organs. The cell cycle analysis showed that the total S-phase of tumor cells in the test intra-arterial treatment group was considerably higher than that of the controls. The weight of the tumor tissues in the group treated by the intra-arterial route (4.06 +/- 2.12 g) was much less than the group treated intravenously (18.25 +/- 8.34 g) ( P<.01). These findings indicated that the administration of GE7/HSV1-tk complex via the ovarian artery route could be a promising avenue of future human ovarian cancer treatment. C1 Fudan Univ, Obstet & Gynecol Hosp, Dept Gynecol, Shanghai 200011, Peoples R China. Fudan Univ, Canc Hosp, Dept Surg, Shanghai 200032, Peoples R China. Fudan Univ, Expt Anim Ctr, Shanghai 200032, Peoples R China. Harvard Univ, Sch Med, Dana Farber Canc Inst, Brigham & Womens Hosp,Dept Obstet & Gynecol, Cambridge, MA 02138 USA. Shanghai Canc Inst, Natl Lab Oncogenes & Related Genes, Shanghai 200032, Peoples R China. RP Xu, CJ (reprint author), Fudan Univ, Obstet & Gynecol Hosp, Dept Gynecol, 419 Fang Xie Rd, Shanghai 200011, Peoples R China. EM fckxu@vnet.citiz.net NR 36 TC 1 Z9 1 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0929-1903 J9 CANCER GENE THER JI Cancer Gene Ther. PD OCT PY 2005 VL 12 IS 10 BP 810 EP 817 DI 10.1038/sj.cgt.7700845 PG 8 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA 964IL UT WOS:000231873000003 PM 15905861 ER PT J AU Hu, M Shivdasani, RA AF Hu, M Shivdasani, RA TI Overlapping gene expression in fetal mouse intestine development and human colorectal cancer SO CANCER RESEARCH LA English DT Article ID RIBOSOMAL-PROTEIN GENES; OLIGONUCLEOTIDE ARRAYS; CLUSTERING ANALYSIS; SERIAL ANALYSIS; TUMOR-MARKERS; PROFILES; MECHANISMS; PATHWAYS; PATTERNS; DATABASE AB Pathways relevant to cancer are well known to overlap with fetal development, as reflected in reactivation of embryonic genes in tumors. However, molecular evidence for this notion has gathered in piecemeal fashion, and systematic approaches have rarely been applied to gauge the extent and global characteristics of the overlap in gene expression between developing tissues and cancer. The fraction of genes that is expressed aberrantly in a given cancer and also developmental in primary function is unknown, and the tissue specificity of recapitulated gene expression remains unexplored. We developed a statistical method to relate expression profiles from human colon cancer and diverse nonintestinal tumors to transcripts that decline in expression with epithelial differentiation in the fetal mouse gut. For genes that are overexpressed in colon cancer, we computed 8% to 19% likelihood that they were expressed transiently during epithelial morphogenesis in intestine development. Among genes dysregulated in other tumors, the corresponding likelihood fell between 1% and 6%. Similarly, low probabilities were obtained when we compared genes not overexpressed in colon cancer with transcriptional profiles in intestine organogenesis. Genes that increase after fetal gut epithelial differentiation were not differentially represented between cancerous and normal colon. Our findings systematically characterize the global extent and tissue specificity of developmental expression programs in colorectal cancer and illustrate the use of such an approach to identify candidate biomarkers and therapeutic targets. C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Shivdasani, RA (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM ramesh_shivdasani@dfci.harvard.edu FU NIDDK NIH HHS [R01DK61139] NR 35 TC 22 Z9 22 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 8715 EP 8722 DI 10.1158/0008-5472 PG 8 WC Oncology SC Oncology GA 968YL UT WOS:000232199400022 PM 16204040 ER PT J AU Jiang, JR Greulich, H Janne, PA Sellers, WR Meyerson, M Griffin, JD AF Jiang, JR Greulich, H Janne, PA Sellers, WR Meyerson, M Griffin, JD TI Epidermal growth factor independent transformation of Ba/F3 cells with cancer-derived epidermal growth factor receptor mutants induces gefitinib-sensitive cell cycle progression SO CANCER RESEARCH LA English DT Article ID TYROSINE KINASE INHIBITOR; HUMAN-BRAIN TUMORS; LUNG-CANCER; STAT ACTIVATION; EGFR MUTATIONS; GENE; ZD1839; MICE; LINE; ERBB AB Epidermal growth factor receptor (EGFR) plays critical roles in many biological processes and in tumorigenesis. Here, we show that two mutated EGFRs found in lung and other malignancies, EGFR-G719S and EGFR-LS58R, could transform Ba/F3 cells to interleukin-3 (IL-3)-independent growth, in a ligand-independent manner, an activity associated with the transforming function of other mutated tyrosine kinases. The mutated receptors are autophosphorylated in the absence of IL-3 without EGF stimulation, and their expression led to the constitutive activation of signal transducers and activators of transcription 5, extracellular signal-regulated kinase 1/2 (ERK1/2), ERK5, and AKT. In wild-type EGFR-expressing Ba/F3 cells, the major EGF-mediated signaling pathways were still intact. Gefitinib inhibited the growth of mutant EGFR-transformed Ba/F3 cells. Strikingly, the gefitinib sensitivity of cells expressing the L858R mutant was significantly greater than that of cells expressing the G719S mutant form, suggesting that distinct EGFR mutations may be differentially sensitive to small-molecule inhibitors. Furthermore, our data showed an antiproliferative effect of gefitinib on the EGFR-transformed Ba/F3 cells. Our results provide a model system to study the function of mutated EGFR and the differential effects of pharmacologic EGFR inhibition on the distinct mutant forms of this tyrosine kinase. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. MIT, Broad Inst, Cambridge, MA USA. Harvard Univ, Cambridge, MA 02138 USA. RP Jiang, JR (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St,Mayer 534, Boston, MA 02115 USA. EM jingrui_jiang@dfci.harvard.edu RI Meyerson, Matthew/E-7123-2012 NR 38 TC 109 Z9 110 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 1 PY 2005 VL 65 IS 19 BP 8968 EP 8974 DI 10.1158/0008-5472.CAN-05-1829 PG 7 WC Oncology SC Oncology GA 968YL UT WOS:000232199400052 PM 16204070 ER PT J AU Shimada, A Kano, J Ishiyama, T Okubo, C Iijima, T Morishita, Y Minami, Y Inadome, Y Shu, YJ Sugita, S Takeuchi, T Noguchi, M AF Shimada, A Kano, J Ishiyama, T Okubo, C Iijima, T Morishita, Y Minami, Y Inadome, Y Shu, YJ Sugita, S Takeuchi, T Noguchi, M TI Establishment of an immortalized cell line from a precancerous lesion of lung adenocarcinoma, and genes highly expressed in the early stages of lung adenocarcinoma development SO CANCER SCIENCE LA English DT Article ID PULMONARY ADENOCARCINOMA; MONOCLONAL-ANTIBODIES; CANCER; ANTIGENS; CARCINOGENESIS; PROGNOSIS; FAMILY; S100A2; TROP-2 AB Atypical adenomatous hyperplasia (AAH) is classified as a precancerous lesion of lung adenocarcinoma. We established an immortalized AAH cell line (PL16T) and a human non-neoplastic bronchial epithelial cell line (PL16B) from the same patient by transfection with the gene for SV40 large T antigen. The expression profile of PL16T was compared with that of PL16B by the suppression subtractive hybridization method. From 704 selectively hybridized clones, we finally selected 25 fragments of mRNA that showed transcription levels more than three times higher in PL16T than in PL16B. Thirteen (52%) and eight (32%) of them encoded tumor-associated calcium signal transducer 2 (TACSTD2) and S100 calcium binding protein A2 (S100A2), respectively. The high transcription of TACSTD2 and S1100A2 in PL16T was confirmed by in situ hybridization. In normal lung tissue, both TACSTD2 and S100A2 were expressed at very low levels, but seven and five of 14 AAH were positive for TACSTD2 and S100A2, respectively. The frequency of TACSTD2 positivity was increased in 16 of 22 bronchioloalveolar carcinomas (BAC) and adenocarcinoma with mixed subtype with BAC component (mixed BAC). Positivity for S100A2 occurred in four of 22 BAC and mixed BAC. The abnormal transcription of TACSTD2 and S100A2 are thought to be unique molecular markers of the preinvasive stage of lung adenocarcinoma. C1 Univ Tsukuba, Grad Sch Comprehens Human Sci, Dept Pathol, Tsukuba, Ibaraki 3058575, Japan. Univ Tsukuba, Grad Sch Comprehens Human Sci, Dept Clin Pathol, Tsukuba, Ibaraki 3058575, Japan. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Natl Inst Agrobiol Sci, Dept Physiol & Genet Regulat, Tsukuba, Ibaraki 3050901, Japan. RP Noguchi, M (reprint author), Univ Tsukuba, Grad Sch Comprehens Human Sci, Dept Pathol, 1-1-1 Tennodai, Tsukuba, Ibaraki 3058575, Japan. EM nmasayuk@md.tsukuba.ac.jp NR 21 TC 17 Z9 19 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1347-9032 J9 CANCER SCI JI Cancer Sci. PD OCT PY 2005 VL 96 IS 10 BP 668 EP 675 DI 10.1111/j.1349-7006.2005.00100.x PG 8 WC Oncology SC Oncology GA 982HX UT WOS:000233149800006 PM 16232198 ER PT J AU Levine, GN Lincoff, AM Ferguson, JJ Mahaffey, KW Goodman, SG Cannon, CP Theroux, P Fox, KAA AF Levine, GN Lincoff, AM Ferguson, JJ Mahaffey, KW Goodman, SG Cannon, CP Theroux, P Fox, KAA TI Utilization of catheterization and revascularization procedures in patients with non-ST segment elevation acute coronary syndrome over the last decade SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE non-ST segment elevation acute coronary syndrome; management ID PLATELET GLYCOPROTEIN IIB/IIIA; INVASIVE CARDIAC PROCEDURES; ACUTE MYOCARDIAL-INFARCTION; UNSTABLE ANGINA; UNITED-STATES; UNFRACTIONATED HEPARIN; RANDOMIZED-TRIAL; PCI-CURE; MANAGEMENT; OUTCOMES AB The degree to which catheterization and revascularization procedures are utilized in patients with non-ST segment elevation acute coronary syndrome (NSTE-ACS) during hospitalization has broad implications with respect to initial pharmacotherapeutic decisions (upfront therapies), treatment and hospital transfer protocols, guideline recommendations, and allocation of training, material, and financial resources. Analysis of data from multiple trials and registries of patients with NSTE-ACS has the potential to assess more broadly utilization of invasive and revascularization procedures and provide a wide angle or bird's-eye view of the management of such patients, complementing the data obtained from any one trial or registry. We therefore undertook a systematic overview of all large trials and registries of patients with NSTE-ACS conducted over the last decade that were deemed appropriate to provide information on catheterization and revascularization procedures. Although not unexpectedly the percentage of patients with NSTE-ACS managed with cardiac catheterization, percutaneous coronary intervention (PCI), and coronary artery bypass grafting varies in different clinical trials and registries, general findings and trends were still discernable from these studies. During the initial treatment period, the majority of patients were ultimately treated with medical therapy alone (e.g., without revascularization). The percentage of those NSTE-ACS patients undergoing diagnostic cardiac catheterization who were then managed with PCI increased over the last decade and now stands at approximately 50%. Of NSTE-ACS patients who undergo revascularization, the percentage of those patients who are revascularized via PCI similarly increased, and PCI is currently the revascularization procedure utilized in approximately three-fourths of patients undergoing revascularization. The percentages of patients undergoing invasive and revascularization procedures were consistently higher in the U.S. cohorts of study subjects when compared to non-U.S. cohorts of study subjects. (c), 2005 Wiley-Liss, Inc. C1 Houston VA Med Ctr, Cardiol Sect, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Univ Texas, Hlth Sci Ctr, Texas Heart Inst, Houston, TX USA. Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27706 USA. Univ Toronto, St Michaels Hosp, Canadian Heart Res Ctr, Toronto, ON M5B 1W8, Canada. Univ Toronto, St Michaels Hosp, Terrence Donnelly Heart Ctr, Toronto, ON M5B 1W8, Canada. Brigham & Womens Hosp, Div Cardiovasc, Thrombolysis Myocardial Infarct Study Grp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Montreal, Montreal Heart Inst, Montreal, PQ H3C 3J7, Canada. Univ Edinburgh, Cardiovasc Res Ctr, Cardiovasc Res Unit, Edinburgh EH8 9YL, Midlothian, Scotland. RP Levine, GN (reprint author), Houston VA Med Ctr, Cardiol Sect, 3C-330,111-B,2002 Holcombe Blvd, Houston, TX 77030 USA. EM glevine@bcm.tmc.edu NR 28 TC 10 Z9 10 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD OCT PY 2005 VL 66 IS 2 BP 149 EP 157 DI 10.1002/ccd.20469 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 971MF UT WOS:000232387600001 PM 16152646 ER PT J AU Wang, L Liu, J Saha, P Huang, JS Chan, L Spiegelman, B Moore, DD AF Wang, L Liu, J Saha, P Huang, JS Chan, L Spiegelman, B Moore, DD TI The orphan nuclear receptor SHP regulates PGC-1 alpha expression and energy production in brown adipocytes SO CELL METABOLISM LA English DT Article ID SMALL-HETERODIMER-PARTNER; NEGATIVE FEEDBACK-REGULATION; ADAPTIVE THERMOGENESIS; TRANSCRIPTIONAL COACTIVATOR; HORMONE-RECEPTOR; BIRTH-WEIGHT; OBESITY; GENE; MICE; MUTATIONS AB Brown adipocytes increase energy production in response to induction of PGC-1 alpha, a dominant regulator of energy metabolism. We have found that the orphan nuclear receptor SHP (NR0B2) is a negative regulator of PGC-1 alpha. expression in brown adipocytes. Mice lacking SHP show increased basal expression of PGC-1 alpha, increased energy expenditure, and resistance to diet-induced obesity. Increased PGC-1 alpha expression in SHP null brown adipose tissue is not due to beta-adrenergic activation, since it is also observed in primary cultures of SHP-/- brown adipocytes that are not exposed to such stimuli. In addition, acute inhibition of SHP expression in cultured wild-type brown adipocytes increases basal PGC-1 alpha expression, and SHP overexpression in SHP null brown adipocytes decreases it. The orphan nuclear receptor ERR gamma is expressed in BAT and its transactivation of the PGC-1 alpha promoter is potently inhibited by SHP. We conclude that SHP functions as a negative regulator of energy production in BAT. C1 Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. Univ Kansas, Ctr Med, Dept Med, Kansas City, KS 66160 USA. Univ Kansas, Ctr Med, Dept Pharmacol, Kansas City, KS 66160 USA. Dana Farber Canc Res Inst, Boston, MA 02115 USA. RP Moore, DD (reprint author), Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. EM moore@bcm.tmc.edu FU NIDDK NIH HHS [P01DK57743, R01DK53366] NR 42 TC 100 Z9 103 U1 1 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 227 EP 238 DI 10.1016/j.cmet.2005.08.010 PG 12 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 974TB UT WOS:000232613200005 PM 16213225 ER PT J AU Yang, YG Wang, H Asavaroengchai, W Dey, BR AF Yang, Yong-Guang Wang, Hui Asavaroengchai, Wannee Dey, Bimalangshu R. TI Role of Interferon-gamma in GVHD and GVL SO CELLULAR & MOLECULAR IMMUNOLOGY LA English DT Review DE GVHD; IFN-gamma; leukemia; transplantation; T cell AB Interferon (IFN)-gamma, a potent proinflammatory cytokine produced by multiple types of cells (e.g., activated T, NK and NKT cells), plays important and complex roles in both innate and adaptive immune responses. There may be a correlation between the IFN-gamma level and GVHD severity in patients receiving allogeneic hematopoietic cell transplantation. However, such a correlation may just reflect the presence of large numbers of activated T cells, and does not necessarily imply a harmful role of IFN-gamma in the pathogenesis of GVHD. There has been increasing experimental evidence that IFN-gamma is not required and may even inhibit GVHD. Paradoxically, IFN-gamma facilitates graft-versus-leukemic (GVL) effects. Thus, IFN-gamma blockade is likely deleterious in patients after allogeneic hematopoietic cell transplantation, and not beneficial as previously suggested. C1 [Yang, Yong-Guang; Wang, Hui; Asavaroengchai, Wannee] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr,Surg Serv, Boston, MA 02129 USA. [Dey, Bimalangshu R.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Bone Marrow Transplant Unit,Dept Med, Boston, MA 02114 USA. RP Yang, YG (reprint author), Massachusetts Gen Hosp, Transplantat Biol Res Ctr, MGH East,Bldg 149-5102,13th St, Boston, MA 02129 USA. EM yongguang.yang@tbrc.mgh.harvard.edu FU American Cancer Society [RSG-03-227-01-LIB] FX We thank Drs Jessica Sachs and Toshiki Saito for critical reading of the manuscript, and Luisa Raleza for expert assistance with the manuscript. Work from the authors' laboratory is supported by a research grant from American Cancer Society (RSG-03-227-01-LIB). NR 81 TC 34 Z9 39 U1 0 U2 1 PU CHIN SOCIETY IMMUNOLOGY PI BEING PA 5 DONGDAN SANTIAO, DONGCHEN DISTRICT, BEING, 100005, PEOPLES R CHINA SN 1672-7681 EI 2042-0226 J9 CELL MOL IMMUNOL JI Cell. Mol. Immunol. PD OCT PY 2005 VL 2 IS 5 BP 323 EP 329 PG 7 WC Immunology SC Immunology GA V32AY UT WOS:000208925300001 PM 16368058 ER PT J AU Moskowitz, MA AF Moskowitz, MA TI Migraine: what is the link between spreading depression and head pain? 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 C1 Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0333-1024 J9 CEPHALALGIA JI Cephalalgia PD OCT PY 2005 VL 25 IS 10 BP 842 EP 843 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 964TD UT WOS:000231902500019 ER PT J AU Tegos, GP Demidova, TN Arcila-Lopez, D Lee, H Wharton, T Gali, H Hamblin, MR AF Tegos, GP Demidova, TN Arcila-Lopez, D Lee, H Wharton, T Gali, H Hamblin, MR TI Cationic fullerenes are effective and selective antimicrobial photosensitizers SO CHEMISTRY & BIOLOGY LA English DT Article ID GRAM-NEGATIVE BACTERIA; ISCHEMIA-REPERFUSED LUNGS; PHOTODYNAMIC THERAPY; IN-VITRO; TOLUIDINE BLUE; LETHAL PHOTOSENSITIZATION; ESCHERICHIA-COLI; BIOLOGICAL APPLICATIONS; PSEUDOMONAS-AERUGINOSA; POLYHYDROXYLATED C-60 AB Fullerenes are soccer ball-shaped molecules composed of carbon atoms, and, when derivatized with functional groups, they become soluble and can act as photosensitizers. Antimicrobial photodynamic therapy combines a nontoxic photosensitizer with harmless visible light to generate reactive oxygen species that kill microbial cells. We have compared the antimicrobial activity of six functionalized C-60 compounds with one, two, or three hydrophilic or cationic groups in combination with white light against gram-positive bacteria, gram-negative bacteria, and fungi. After a 10 min incubation, the bis- and tris-cationic fullerenes were highly active in killing all tested microbes (4-6 logs) under conditions in which mammalian cells were comparatively unharmed. These compounds performed significantly better than a widely used antimicrobial photosensitizer, toluidine blue O. The high selectivity and efficacy exhibited by these photosensitizers encourage further testing for antimicrobial applications. C1 Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. Tufts Univ, Cell Mol & Dev Biol Program, Boston, MA 02111 USA. Lynntech Inc, College Stn, TX 77840 USA. Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu RI Tegos, George/C-8830-2011; OI Hamblin, Michael/0000-0001-6431-4605 FU NCI NIH HHS [R43 CA103268]; NIAID NIH HHS [R01 AI050875, R01 AI050875-01A2, R01 AI050875-02] NR 64 TC 111 Z9 118 U1 2 U2 34 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-5521 J9 CHEM BIOL JI Chem. Biol. PD OCT PY 2005 VL 12 IS 10 BP 1127 EP 1135 DI 10.1016/j.chembiol.2005.08.014 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 981GZ UT WOS:000233077000011 PM 16242655 ER PT J AU Mortensen, E Restrepo, M Anzueto, A Pugh, J AF Mortensen, E Restrepo, M Anzueto, A Pugh, J TI Impact of guideline-concordant antibiotic therapy on mortality within 48 hours of admission for patients hospitalized with community-acquired pneumonia SO CHEST LA English DT Meeting Abstract CT Chest 2005 Conference CY OCT 29-NOV 03, 2005 CL Montreal, CANADA C1 S Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD OCT PY 2005 VL 128 IS 4 SU S BP 148S EP 148S PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 977JT UT WOS:000232800300061 ER PT J AU Mularski, RA Asch, SM Shrank, WH Kerr, EA Setodji, C Adams, J Keesey, J McGlynn, EA AF Mularski, RA Asch, SM Shrank, WH Kerr, EA Setodji, C Adams, J Keesey, J McGlynn, EA TI The quality of health care delivered to Americans with obstructive lung disease SO CHEST LA English DT Meeting Abstract CT Chest 2005 Conference CY OCT 29-NOV 03, 2005 CL Montreal, CANADA C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD OCT PY 2005 VL 128 IS 4 SU S BP 179S EP 179S PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 977JT UT WOS:000232800300154 ER PT J AU Sahara, I Shoji, T Muniappan, A Guenther, DA Wain, JC Houser, SL Pujara, A Bravard, MA Sachs, DH Madsen, JC Allan, JS AF Sahara, I Shoji, T Muniappan, A Guenther, DA Wain, JC Houser, SL Pujara, A Bravard, MA Sachs, DH Madsen, JC Allan, JS TI The induction of robust tolerance in an MHC-mismatched porcine pulmonary allograft model prevents obliterative bronchiolitis SO CHEST LA English DT Meeting Abstract CT Chest 2005 Conference CY OCT 29-NOV 03, 2005 CL Montreal, CANADA C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD OCT PY 2005 VL 128 IS 4 SU S BP 211S EP 211S PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 977JT UT WOS:000232800300248 ER PT J AU Jones, SF Cooper, JA Dransfield, MT AF Jones, SF Cooper, JA Dransfield, MT TI Single measurements of inspiratory capacity are not better than FEV1 in predicting symptom scores in COPD SO CHEST LA English DT Meeting Abstract CT Chest 2005 Conference CY OCT 29-NOV 03, 2005 CL Montreal, CANADA C1 Birmingham VA Med Ctr, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD OCT PY 2005 VL 128 IS 4 SU S BP 247S EP 248S PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 977JT UT WOS:000232800301010 ER PT J AU Mularski, RA Mularski, KS Asch, SM AF Mularski, RA Mularski, KS Asch, SM TI Hazards of opiate mismanagement in the ICU SO CHEST LA English DT Meeting Abstract CT Chest 2005 Conference CY OCT 29-NOV 03, 2005 CL Montreal, CANADA C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD OCT PY 2005 VL 128 IS 4 SU S BP 419S EP 420S PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 977JT UT WOS:000232800302139 ER PT J AU Levine, M Iliescu, ME Margellos-Anast, H Estarziau, M Ansell, DA AF Levine, M Iliescu, ME Margellos-Anast, H Estarziau, M Ansell, DA TI The effects of cocaine and heroin use on intubation rates and hospital utilization in patients with acute asthma exacerbations SO CHEST LA English DT Article DE asthma; cocaine; drug abuse; heroin; intubation; status asthmaticus ID SUBSTANCE-ABUSE; ASSOCIATION; BRONCHOSPASM; INSUFFLATION; SMOKING; DEATHS AB Background: The use of both heroin and cocaine has been associated with asthma exacerbations. However, the magnitude of this effect has not been adequately described. The purpose of this study was to examine the association between cocaine or heroin use and asthma severity. Methods: We conducted a retrospective chart review of adult patients who had been admitted to an inner-city hospital and who subsequently had received a hospital discharge diagnosis of acute asthma exacerbation. Patients were classified as cocaine users if they had admitted to using cocaine within 24 h of symptom onset, or if a positive drug screen result was obtained. A similar classification was employed for heroin. The severity of asthma exacerbations among cocaine and heroin users was compared to severity among nonusers (ie, individuals without evidence of having used either drug within the 24 h preceding symptom onset). Results: One hundred sixty-six unique patient encounters were identified, and 152 patient records were analyzed. Of these, 27.6% (42 of 152 patients) used cocaine with or without heroin and were classified as cocaine users, while 30.9% (47 of 152 patients) used heroin with or without cocaine and were classified as heroin users. Cocaine users had longer mean lengths of hospital stay than nonusers (3.4 days vs 2.5 days; p < 0.049). Intubation and ICU admission were more common among cocaine users than nonusers (21.4% vs 2.3%, respectively [p = 0.0006]; 31.0% vs 11.5%, respectively [p = 0.0068]). Heroin users were also intubated more frequently than nonusers (17.0% vs 2.3%, respectively; p = 0.0036). Neither the length of hospital stay nor the percentage of ICU admissions was significantly different between heroin users and nonusers. Conclusion: Heroin and cocaine use are common among adult asthmatic patients admitted to an inner-city hospital. Both cocaine and heroin are significantly associated with the need for intubation. Based on these findings, it may be prudent to screen adults with asthma presenting to an urban emergency department for cocaine and heroin use. C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Rosalind Franklin Univ Med & Sci, Chicago Med Sch, Chicago, IL USA. Mt Sinai Hosp, Dept Med, Chicago, IL USA. Mt Sinai Hosp, Sinai Urban Hlth Inst, Chicago, IL USA. RP Levine, M (reprint author), Brigham & Womens Hosp, 75 Francis St,Neville House,2nd Floor, Boston, MA 02115 USA. EM mdlevine@partners.org NR 36 TC 27 Z9 27 U1 0 U2 1 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD OCT PY 2005 VL 128 IS 4 BP 1951 EP 1957 DI 10.1378/chest.128.4.1951 PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 975RK UT WOS:000232679400012 PM 16236840 ER PT J AU Ariyarajah, V Mercado, K Apiyasawat, S Puri, P Spodick, DH AF Ariyarajah, V Mercado, K Apiyasawat, S Puri, P Spodick, DH TI Correlation of left atrial size with P-wave duration in interatrial block SO CHEST LA English DT Article DE echocardiogram; formula; interatrial block; left atrial enlargement; P-wave duration ID GENERAL-HOSPITAL POPULATION; ECHOCARDIOGRAPHY; ENLARGEMENT; CONDUCTION; PREVALENCE; CRITERIA AB Background: Interatirial block (LAB) [P-wave duration >= 110 ms] is associated with left atrial (LA) enlargement (LAE) and pathophysiologic derangements that result in atrial tachyarrhythmias, LA electromechanical dysfunction, and embolism. However, there has been no study addressing the direct correlation of P-wave duration in LAB and LAE. Methods: One hundred eighty-one consecutive patients who were admitted to a tertiary care teaching hospital over 5 consecutive days were screened for past transthoracic echocardiogram evaluations and were then matched with ECGs done within 10 days of these echocardiographic investigations. ECGs were evaluated for presence of IAB, and patients were subsequently classified into two groups: control patients and patients with LAB. Patients were also matched for common comorbidities. Mean, SD of age, Pearson correlation coefficient (r), p values, and multivariate and linear regression analyses were analyzed for the investigated variables of LA size, left ventricular hypertrophy (LVH), posterior wall thickness, septal thickness, and P-wave duration. Results: From the sample (n = 66; mean age +/- SD, 71.3 +/- 13.7; female gender, 48.5%), the mean LA size in the control group was 36.7 +/- 4.01 mm and for the group of patients with IAB (n = 38) was 42.2 +/- 7.25 mm (p = 0.004). Linear regression analysis revealed that P-wave duration was significantly correlated with LA size (p = 0.0002, r = 0.606). Conclusions: Degree of conduction delay in IAB (P-wave duration) is an independent, direct correlate of LAE, and the regression equation (LA size [in millimeters] = 2.47 +/- 0.29 x P-wave duration [in milliseconds]) could be used to estimate LAE. C1 VA Boston Hlth Care Syst, MAVERIC, Boston, MA 02130 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. St Vincent Hosp, Div Cardiol, Worcester, MA 01604 USA. St Vincent Hosp, Dept Med, Worcester, MA 01604 USA. Univ Massachusetts, Sch Med, Div Cardiovasc Med, Worcester, MA 01605 USA. RP Ariyarajah, V (reprint author), VA Boston Hlth Care Syst, MAVERIC, 150 S Huntington Ave, Boston, MA 02130 USA. EM vignendra@hotmail.com NR 15 TC 38 Z9 39 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD OCT PY 2005 VL 128 IS 4 BP 2615 EP 2618 DI 10.1378/chest.128.4.2615 PG 4 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 975RK UT WOS:000232679400105 PM 16236933 ER PT J AU Hoo, GWS Wen, YE Nguyen, TV Goetz, MB AF Hoo, GWS Wen, YE Nguyen, TV Goetz, MB TI Impact of clinical guidelines in the management of severe hospital-acquired pneumonia SO CHEST LA English DT Article DE guidelines; nosocomial pneumonia; ventilator-associated pneumonia ID VENTILATOR-ASSOCIATED PNEUMONIA; INTENSIVE-CARE-UNIT; INADEQUATE ANTIMICROBIAL TREATMENT; NOSOCOMIAL PNEUMONIA; ATTRIBUTABLE MORTALITY; ANTIBIOTIC-TREATMENT; DIAGNOSTIC-ACCURACY; RESISTANT-BACTERIA; STRATEGY; THERAPY AB Study objectives: To asses the impact of locally developed antimicrobial treatment guidelines in the initial empiric treatment of ICU patients with severe hospital-acquired pneumonia (HAP). Design: Observational cohort study with preguideline and postguideline data collection. Patients: A total of 48 preguideline patients with 56 episodes of severe HAP defined by the National Nosocomial Infections Surveillance (NNIS) compared with 58 guideline-treated (GUIDE) patients with 61 episodes of severe HAP. Results: The two groups were similar in terms of mean (+/- SD) age (NNIS group, 67.7 +/- 9.6 years; GUIDE group, 68.0 +/- 11.5 years) and simplified acute physiology score (NNIS group, 12.9 +/- 3.9; GUIDE group, 12.6 +/- 3.1) at the HAP diagnosis, and the proportion of the most frequent isolates (ie, Pseudomonas and methicillin-resistant Staphylococcus aureus). There was wide variation in initial antibiotic use in NNIS-treated patients, with cefotaxime, ceftazidime, and piperacillin being the most common agents compared with all of the GUIDE patients who received an imipenem-cilastin-based regimen. Vancomycin use was similar in both groups. The GUIDE patients had a higher percentage of adequately treated patients (SI% vs 46%, respectively; p < 0.01) with a lower mortality rate at 14 days (8% vs 23%, respectively; p = 0.03). A lower mortality rate was also noted at the end of 30 days and the end of hospitalization but was not statistically significant. Appropriate imipenem use (as defined by the guidelines) occurred in 74% of the cases, and there was no increase in the number of imipenem-resistant organisms isolated during the course of the study. Conclusions: These guidelines represent a successful implementation of a "deescalation" approach, because the recommended empiric therapy with broad-spectrum antibiotics was switched to therapy with narrower spectrum agents after 3 days. Based on our experience, this approach improves the adequacy of antibiotic treatment, with improvement in short-term survival and without increasing the emergence of resistant organisms. C1 Univ Calif Los Angeles, Pulm & Crit Care Sect, Geffen Sch Med, VA Greater Los Angeles Healthcare Syst,W Los Ange, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Infect Dis Sect, Geffen Sch Med, VA Greater Los Angeles Healthcare Syst,W Los Ange, Los Angeles, CA 90073 USA. RP Hoo, GWS (reprint author), Univ Calif Los Angeles, Pulm & Crit Care Sect, Geffen Sch Med, VA Greater Los Angeles Healthcare Syst,W Los Ange, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM Guy.Soohoo@med.va.gov OI Goetz, Matthew/0000-0003-4542-992X NR 38 TC 88 Z9 93 U1 0 U2 1 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD OCT PY 2005 VL 128 IS 4 BP 2778 EP 2787 PG 10 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 975RK UT WOS:000232679400127 PM 16236955 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 Anderson, PM Wiseman, GA Erlandson, L Rodriguez, V Trotz, B Dubansky, SA Albritton, K AF Anderson, PM Wiseman, GA Erlandson, L Rodriguez, V Trotz, B Dubansky, SA Albritton, K TI Gemcitabine radiosensitization after high-dose samarium for osteoblastic osteosarcoma SO CLINICAL CANCER RESEARCH LA English DT Article ID ACTIVITY SAMARIUM-153-EDTMP THERAPY; DIAMINE TETRAMETHYLENE PHOSPHONATE; HIGH-GRADE OSTEOSARCOMA; PHASE-I TRIAL; NONMETASTATIC OSTEOSARCOMA; UNRESECTABLE OSTEOSARCOMA; PANCREATIC ADENOCARCINOMA; NEOADJUVANT CHEMOTHERAPY; SKELETAL IRRADIATION; PROGNOSTIC-FACTORS AB Osteoblastic metastases and osteosarcoma can avidly concentrate bone-seeking radiopharmaceuticals. We sought to increase effectiveness of high-dose 153 Samarium ethylenediaminetetramethylene phosphonate (Sm-153-EDTMP, Quadramet) on osteosarcomas using a radiosensitizer, gemcitabine. Fourteen patients with osteoblastic lesions were treated with 30 mCi/kg (SM)-S-153- EDTMP. Gemcitabine was administered 1 day after samarium infusion. Residual total body radioactivity was within the safe range of < 3.6 mCi on day +14 (1.1 +/- 0.4 mCi; range, 0.67-1.8 mCi). All patients received autologous stem cell reinfusion 2 weeks after (SM)-S-153 to correct expected grade 4 hematopoietic toxicity. Peripheral blood progenitor cells were infused in 11 patients; three patients had marrow infused. Blood count recovery was uneventful after peripheral blood progenitor cells in 11 of 11 patients. Toxicity from a single infusion of gemcitabine (1,500 mg/m(2)) in combination with Sm-153-EDTIVIP was minimal (pancytopenia). However, toxicity from a daily gemcitabine regimen (250 mg/m(2) /d x 4-5 days) was excessive (grade 3 mucositis) in one of two patients. There were no reported episodes of hemorrhagic cystitis (hematuria) or nephrotoxicity. At the 6- to 8-week follow-up, there were six partial remissions, two mixed responses, and six patients with progressive disease. In the 12 patients followed > 1 year, there have been no durable responses. Thus, although high-dose Sm-153-EDTMP + gemcitabine has moderate palliative activity (improved pain; radiologic responses) in this poor-risk population, additional measures of local and systemic control are required for durable control of relapsed osteosarcoma with osteoblastic lesions. The strategy of radioactive drug binding to a target followed by a radiosensitizer may provide synergy and improved response rate. C1 MD Anderson Canc Ctr, Unit 87, Houston, TX 77030 USA. Mayo Clin, Rochester, MN USA. SUNY Upstate Med Univ, Syracuse, NY USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Anderson, PM (reprint author), MD Anderson Canc Ctr, Unit 87, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM pmanders@mdanderson.org NR 50 TC 45 Z9 46 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT 1 PY 2005 VL 11 IS 19 BP 6895 EP 6900 DI 10.1158/1078-0432.CCR-05-0628 PN 1 PG 6 WC Oncology SC Oncology GA 969MK UT WOS:000232238100023 PM 16203780 ER PT J AU O'Hare, T Walters, DK Stoffregen, EP Sherbenou, DW Heinrich, MC Deininger, MWN Druker, BJ AF O'Hare, T Walters, DK Stoffregen, EP Sherbenou, DW Heinrich, MC Deininger, MWN Druker, BJ TI Combined AN inhibitor therapy for minimizing drug resistance in chronic myeloid leukemia: Src/Abl inhibitors are compatible with imatinib SO CLINICAL CANCER RESEARCH LA English DT Article ID ABL KINASE INHIBITOR; CHRONIC MYELOGENOUS LEUKEMIA; BCR-ABL; TYROSINE KINASE; CHRONIC-PHASE; PHILADELPHIA-CHROMOSOME; CYTOGENETIC RESPONSES; DOMAIN MUTATIONS; BLAST CRISIS; WILD-TYPE AB Purpose: Chronic myeloid leukemia (CML) is effectively treated with imatinib. However, reactivatiori of Bcr-Abl via kinase domain mutations that reduce sensitivity to imatinib can cause relapse. As combination therapy is frequently used to prevent emergence of resistance, the combination of imatinib with an inhibitor of imatinib-resistant Bcr-Abl mutants (e.g., Src/Abl inhibitors AP23848 and BMS-354825) was investigated. Experimental Design: To test this approach, cellular proliferation and Bcr-Abl tyrosine phosphorylation assays were done on Ba/F3 cells expressing wild-type (WT) Bcr-Abl and four common imatinib-resistant mutants (Y253F, E255K,T315I, and M351T). Colony-forming assays with primary CML cells were also done. Results: Both Src/Abl inhibitors retained full inhibitory capacity when coadministered with imatinib at concentrations above typical clinical levels. For cells expressing WT Bcr-Abl or the marginally imatinib-resistant mutant M351T, inclusion of imatinib at therapeutic levels enhanced the effects of the Src/Abl inhibitors. By comparison, for the highly imatinib-resistant mutants Y253F and E255K, inclusion of imatinib at clinical levels resulted in only a slight enhancement beyond the effects of the Src/Abl inhibitors. None of the inhibitors affected Bcr-Abl T315I cells. Colony-forming assays with primary CML cells yielded analogous results. Conclusions: Our results indicate that Src/Abl inhibitors are compatible with imatinib and suggest that combined Abl inhibitor therapy is a feasible treatment strategy for patients with CML. C1 Oregon Hlth Sci Univ, Howard Hughes Med Inst, Portland, OR 97239 USA. Oregon Hlth Sci Univ, Inst Canc, Div Hematol & Med Oncol, Portland, OR 97239 USA. Portland Vet Affairs Med Ctr, Portland, OR USA. RP O'Hare, T (reprint author), Oregon Hlth Sci Univ, Howard Hughes Med Inst, L592,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM oharet@ohsu.edu NR 38 TC 72 Z9 77 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 6987 EP 6993 DI 10.1158/1078-0432.CCR-05-0622 PN 1 PG 7 WC Oncology SC Oncology GA 969MK UT WOS:000232238100035 PM 16203792 ER PT J AU LoTempio, MM Veena, MS Steele, HL Ramamurthy, B Ramalingam, TS Cohen, AN Chakrabarti, R Srivatsan, ES Wang, MB AF LoTempio, MM Veena, MS Steele, HL Ramamurthy, B Ramalingam, TS Cohen, AN Chakrabarti, R Srivatsan, ES Wang, MB TI Curcumin suppresses growth of head and neck squamous cell carcinoma SO CLINICAL CANCER RESEARCH LA English DT Article ID NF-KAPPA-B; QUALITY-OF-LIFE; BCL-X-L; IN-VITRO; GENE-THERAPY; CANCER CELLS; MEDIATED APOPTOSIS; SURVIVAL; DIFERULOYLMETHANE; CARCINOGENESIS AB Purpose: The purpose of this study was to determine whether curcumin would trigger cell death in the head and neck squamous cell carcinoma (HNSCC) cell lines CCL 23, CAL 27, and UM-SCC1 in a dose-dependent fashion. Experimental Design: HNSCC cells were treated with curcumin and assayed for in vitro growth suppression using 3-(4,5-dimethylthiozol-2-yl)-2,5-diphenyl tetrazolium bromide and fluorescence-activated cell sorting analyses. Expression of p16, cyclin D1, phospho-I kappa beta, and nuclear factor-kappa beta (NF-kappa beta) were measured by Western blotting, gel shift, and immunofluorescence. Results: Addition of curcumin resulted in a dose-dependent growth inhibition of all three cell lines. Curcumin treatment resulted in reduced nuclear expression of NF-kappa beta. This effect on NF-kappa beta was further reflected in the decreased expression of phospho-I kappa beta-alpha. Whereas the expression of cyclin D1, an NF-kappa beta-activated protein, was also reduced, there was no difference in the expression of p16 at the initial times after curcumin treatment. In vivo growth studies were done using nude mice xenograft tumors. Curcumin was applied as a noninvasive topical paste to the tumors and inhibition of tumor growth was observed in xenografts from the CAL27 cell line. Conclusions: Curcumin treatment resulted in suppression of HNSCC growth both in vitro and in vivo. Our data support further investigation into the potential use for curcumin as an adjuvant or chemopreventive agent in head and neck cancer. C1 Univ Calif Los Angeles, Div Head & Neck Surg, David Geffen Sch Med, Los Angeles, CA 90095 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Dept Surg, Los Angeles, CA USA. RP Wang, MB (reprint author), Univ Calif Los Angeles, Div Head & Neck Surg, David Geffen Sch Med, CHS 62-132,10833 Le Conte Ave, Los Angeles, CA 90095 USA. EM mbwang@ucla.edu NR 46 TC 100 Z9 106 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 6994 EP 7002 DI 10.1158/1078-0432.CCR-05.0301 PN 1 PG 9 WC Oncology SC Oncology GA 969MK UT WOS:000232238100036 PM 16203793 ER PT J AU Pratt, DS Trainer, TD Krawitt, EL AF Pratt, DS Trainer, TD Krawitt, EL TI Heterozygous alpha(1)-antitrypsin deficiency and chronic hepatitis C SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Univ Vermont, Dept Pathol, Burlington, VT 05405 USA. Univ Vermont, Dept Med, Burlington, VT 05405 USA. RP Pratt, DS (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. NR 2 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD OCT PY 2005 VL 3 IS 10 BP XXIX EP XXIX DI 10.1053/S1542-3565(05)00360-5 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 995NC UT WOS:000234106000002 PM 16234035 ER PT J AU Khalid, A McGrath, KM Zahid, M Wilson, M Brody, D Swalsky, P Moser, AJ Lee, KK Slivka, A Whitcomb, DC Finkelstein, S AF Khalid, A McGrath, KM Zahid, M Wilson, M Brody, D Swalsky, P Moser, AJ Lee, KK Slivka, A Whitcomb, DC Finkelstein, S TI The role of pancreatic cyst fluid molecular analysis in predicting cyst pathology SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article ID TUMOR-SUPPRESSOR GENE; INTRAEPITHELIAL NEOPLASIA; LESIONS; P53; ADENOCARCINOMA; EXPRESSION; MUTATIONS; DIAGNOSIS; CANCER; DPC4 AB Background & Aims: Current methods to detect malignancy in mucinous cystic neoplasms of the pancreas remain inadequate. The role of detailed molecular analysis in this context was investigated. Methods: Endoscopic ultrasound-guided pancreatic cyst aspirates were prospectively collected during a period of 19 months and studied for cytology, carcinoembryonic antigen level, and molecular analysis. Molecular evaluation incorporated DNA quantification (amount and quality), k-ras point mutation, and broad panel tumor suppressor linked microsatellite marker allelic loss analysis by using fluorescent capillary electrophoresis. The sequence of mutation acquisition was also calculated on the basis of a clonal expansion model, and comparison was made to the final pathology. Results: Thirty-six cysts with confirmed histology were analyzed. There were 11 malignant, 15 premalignant, and 10 benign cysts. Malignant cysts could be differentiated from premalignant cysts on the basis of fluid carcinoembryonic antigen level (P =.034), DNA quality (P =.009), number of mutations (P =.002), and on the sequence of mutations acquired (P <.001). Early k-ras mutation followed by allelic loss was the most predictive of a malignant cyst (sensitivity, 91%; specificity, 93%). Conclusions: Malignant cyst fluid contains adequate DNA to allow mutational analysis. A first hit k-ras mutation followed by allelic loss is most predictive of the presence of malignancy in a pancreatic cyst. This approach should serve as an ancillary tool to the conventional work-up of pancreatic cysts. Cumulative amount and timing of detectable mutational damage can assist in diagnosis and clinical management. C1 Univ Pittsburgh, Med Ctr, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA 15213 USA. Univ Pittsburgh, VA Pittsburgh Hlth Care Syst, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Dept Med, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Dept Surg, Pittsburgh, PA 15213 USA. Redpath Integrated Pathol, Pittsburgh, PA USA. RP Khalid, A (reprint author), Univ Pittsburgh, Med Ctr, Div Gastroenterol Hepatol & Nutr, M2,C Wing,PUH,200 Lothrop St, Pittsburgh, PA 15213 USA. EM khalida@upmc.edu NR 21 TC 126 Z9 127 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD OCT PY 2005 VL 3 IS 10 BP 967 EP 973 DI 10.1053/S1542-3565(05)00409-X PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 995NC UT WOS:000234106000008 PM 16234041 ER PT J AU Jo, WS Bandipalliam, P Shannon, KM Niendorf, KB Chan-Smutko, G Hur, C Syngal, S Chung, DC AF Jo, WS Bandipalliam, P Shannon, KM Niendorf, KB Chan-Smutko, G Hur, C Syngal, S Chung, DC TI Correlation of polyp number and family history of colon cancer with germline MYH mutations SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article ID SOMATIC G-C->T-A MUTATIONS; ONSET COLORECTAL-CANCER; ADENOMATOUS POLYPOSIS; GENE-MUTATIONS; RISK AB Background & Aims: Affected individuals with biallelic MYH mutations are believed to display multiple adenomatous polyps without evidence of vertical transmission. Our goal was to determine the detection rate of germline MYH mutations in a high-risk gastrointestinal cancer clinic population by using polyp number as a selection criterion. Methods: Patients were screened for the 2 most common MYH mutations: Y165C and G382D. The complete MYH coding region was sequenced in cases with a heterozygous mutation. Results: Among 45 patients with more than 15 adenomatous polyps not diagnosed with familial adenomatous polyposis, 7 (15.6%) had biallelic MYH mutations. When 122 participants from a high-risk gastrointestinal cancer clinic who did not fulfill these criteria were tested, 2 additional patients with biallelic mutations were identified. Both had young-onset colorectal cancer (age, <50 y) with fewer than 15 polyps. Surprisingly, most of the 9 patients with biallelic MYH mutations reported family histories consistent with the hereditary nonpolyposis colorectal cancer syndrome (HNPCC), with 7 cases meeting at least I of the Bethesda criteria, 5 cases fulfilling 3 Bethesda criteria, and 2 cases fulfilling the Amsterdam 11 criteria. Conclusions: Most individuals with MYH mutations exhibit multiple adenomatous polyps. However, 22% of cases were missed when this was the sole criterion for germline testing. A significant number reported a strong family history of cancer that was consistent with HNPCC. MYH testing thus can be considered for patients who meet clinical criteria for HNPCC in the absence of DNA mismatch repair gene mutations. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Risk Anal,Canc Ctr,Dept Med, Boston, MA 02114 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med,Gastroenterol Div, Dana Farber Canc Inst,Populat Sci Div, Boston, MA 02115 USA. RP Chung, DC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, 50 Blossom St, Boston, MA 02114 USA. EM chung.daniel@mgh.harvard.edu NR 20 TC 39 Z9 40 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD OCT PY 2005 VL 3 IS 10 BP 1022 EP 1028 DI 10.1053/S1542-3565(05)00411-8 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 995NC UT WOS:000234106000016 PM 16234049 ER PT J AU Spiegel, BMR Chen, K Chiou, CF Robbins, S Younossi, ZM AF Spiegel, BMR Chen, K Chiou, CF Robbins, S Younossi, ZM TI Erythropoietic growth factors for treatment-induced anemia in hepatitis C: A cost-effectiveness analysis SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article ID QUALITY-OF-LIFE; INTERFERON-ALPHA-2B PLUS RIBAVIRIN; HCV-INFECTED PATIENTS; INITIAL TREATMENT; VIROLOGICAL RESPONSE; COMBINATION THERAPY; ESOPHAGEAL-VARICES; SUSTAINED RESPONSE; RANDOMIZED-TRIAL; NATURAL-HISTORY AB Background & Aims: Treatment-induced anemia undermines the efficacy of antiviral therapy in hepatitis C by mandating ribavirin dose reduction and diminishing adherence to therapy. Erythropoietic growth factors (EGFs) may correct treatment-induced anemia, facilitate maintenance of full-dose therapy, and improve rates of sustained virologic response (SVR). We sought to determine the cost effectiveness of adjunctive treatment with an EGF vs standard care in the treatment of hepatitis C. Methods: We used a decision analysis to calculate the cost effectiveness of 2 treatment strategies for a patient cohort with chronic hepatitis C, increased transaminase levels, and no cirrhosis who were receiving pegylated-interferon and ribavirin (RBV): (1) RBV dose-reduction for anemia, followed by discontinuation of therapy if anemia persisted (standard care strategy), (2) adjunctive treatment with EGF therapy for anemia, with RBV dose reduction reserved for persistent anemia despite EGF therapy (EGF strategy). We conducted cost-effectiveness and cost-utility analyses to compare short- and long-term outcomes between the strategies. Results: The percentage achieving SVR was 52.3% in the standard care strategy and 59.5% in the EGF strategy. Compared with standard care, the EGF strategy cost an incremental $36,568 per unadjusted life-year gained and $16,443 per quality-adjusted life-year gained. In a sensitivity analysis, if a third-party payer was willing to pay $50,000 per quality-adjusted life-year gained for the use of an EGF, then 86.1% of patients would be within the budget. Conclusions: Compared with standard care, adjunctive therapy with an EGF for the management of treatment-induced anemia may increase the probability of achieving SVR, increase unadjusted lifespan, and increase quality-adjusted lifespan at an acceptable cost. C1 Univ Calif Los Angeles, UCLA VA Ctr Outcomes Res & Educ, David Geffen Sch Med,Div Digest Dis, VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. VA Greater Los Angeles Healthcare Syst, Div Gastroenterol, Los Angeles, CA USA. Cerner Hlth Insights, Beverly Hills, CA USA. Amgen Inc, Global Hlth Econ, Thousand Oaks, CA 91320 USA. Inova Fairfax Hosp, Annandale, VA USA. RP Spiegel, BMR (reprint author), Univ Calif Los Angeles, UCLA VA Ctr Outcomes Res & Educ, David Geffen Sch Med,Div Digest Dis, VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd,Bldg 115,Room 215E, Los Angeles, CA 90073 USA. EM bspiegel@mednet.ucla.edu NR 50 TC 22 Z9 23 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD OCT PY 2005 VL 3 IS 10 BP 1034 EP 1042 DI 10.1053/S1542-3565(05)00695-6 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 995NC UT WOS:000234106000018 PM 16234051 ER PT J AU Burrell, SC Fischman, AJ AF Burrell, SC Fischman, AJ TI Myelofibrosis on F-18 FDG PET imaging SO CLINICAL NUCLEAR MEDICINE LA English DT Editorial Material DE F-18 fluorodeoxyglucose; positron emission tomography; myelofibrosis ID BONE-SCAN C1 QEII Hlth Sci Ctr, Dept Diagnost Radiol, Halifax, NS B3H 3A7, Canada. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Nucl Med, Boston, MA 02114 USA. RP Burrell, SC (reprint author), QEII Hlth Sci Ctr, Dept Diagnost Radiol, 1796 Summer St, Halifax, NS B3H 3A7, Canada. EM sburrell@dal.ca NR 8 TC 27 Z9 27 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0363-9762 J9 CLIN NUCL MED JI Clin. Nucl. Med. PD OCT PY 2005 VL 30 IS 10 BP 674 EP 674 DI 10.1097/01.rlu.0000178029.47624.66 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 966US UT WOS:000232048400006 PM 16166839 ER PT J AU Mankin, HJ Hornicek, FJ AF Mankin, HJ Hornicek, FJ TI Treatment of giant cell tumors with allograft transplants - A 30-year study SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID TERM-FOLLOW-UP; OSTEOARTICULAR ALLOGRAFTS; BONE ALLOGRAFTS; ADJUVANT CHEMOTHERAPY; IMMUNE-RESPONSES; RESECTION; EXCISION; RECONSTRUCTION; REPLACEMENT; RECURRENCE AB We retrospectively reviewed 144 patients with giant cell tumors who had resection and implantation of cadaveric allografts from 1971-2001. Most procedures were done in the distal femur, proximal tibia, proximal femur, and proximal humerus. Seventy-eight percent of patients have retained their grafts and remain functional, but with limitations. Tumor complications included local recurrences (eight patients, none required an amputation) and metastases (three patients). None of the patients died. Allograft fracture occurred in 30 (21%) of the 144 patients, nonunion occurred in 12 (8%) patients, and infection occurred in 12 (8%) patients. Only patients with infection had a marked decline in outcome. Four patients required amputations, and only two of the eight patients with infection (17%) retained a functional graft. Eighty of the 144 patients (56%) had no complications, with a 94% success rate for the procedure. There have been fewer grafts done with the advent of burring, phenolization, and insertion of polymethylmethacrylate. However, based on our data and the good outcome for more extensive and destructive tumors, allograft implants can be used for treatment of patients with aggressive tumors, tumors that have caused fractures, or tumors that have recurred after conservative treatment. Level of Evidence: Therapeutic study, Level IV (case series). See the Guidelines for Authors for a complete description of levels of evidence. C1 Massachusetts Gen Hosp, Orthopaed Oncol Serv, Boston, MA 02114 USA. RP Mankin, HJ (reprint author), Massachusetts Gen Hosp, Orthopaed Oncol Serv, Boston, MA 02114 USA. EM hmankin@partners.org NR 56 TC 23 Z9 29 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD OCT PY 2005 IS 439 BP 144 EP 150 DI 10.1097/01.blo.0000174684.85250.b5 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 972MK UT WOS:000232457700029 PM 16205153 ER PT J AU Lersundi, A Mankin, HJ Mourikis, A Hornicek, FJ AF Lersundi, A Mankin, HJ Mourikis, A Hornicek, FJ TI Chondromyxoid fibroma - A rarely encountered and puzzling tumor SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article ID BONE; SPINE; CHONDROBLASTOMA AB Chondromyxoid fibroma is an uncommon bone neoplasm, accounting in our series for less than 1% of all connective tissue tumors. The tumor is more common in males, and located mostly in the metaphyseal areas of the lower extremity. The tumor is benign and there have been no reports of metastases. The method of treatment that has been used since the initial identification of the tumor has been curettage, which has a 20-25% recurrence rate. In our 30 patients, the average length of followup was 11 years (range, 1-29 years. Most of the tumors were in the pelvis, proximal tibia, distal femur, and foot. Tumors that were treated with curettage alone did less well than those that were packed with allograft bone or polymethyltriethacrylate. Tumors treated by excision did not recur. The most difficult problem with chondromyxoid fibroma is pathologic identity because it often is confused with more aggressive tumors that may metastasize. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Oncol Serv, Boston, MA 02114 USA. RP Mankin, HJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Orthopaed Oncol Serv, Boston, MA 02114 USA. EM hmankin@partners.org NR 34 TC 11 Z9 11 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-921X J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD OCT PY 2005 IS 439 BP 171 EP 175 DI 10.1097/01.blo.0000174685.62379.6a PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 972MK UT WOS:000232457700032 ER PT J AU Spencer, TJ Biederman, J Wilens, TE AF Spencer, TJ Biederman, J Wilens, TE TI Efficacy and tolerability of long-term, open-label, mixed amphetamine salts extended realease in adolescents with ADHD SO CNS SPECTRUMS LA English DT Article ID ATTENTION-DEFICIT/HYPERACTIVITY-DISORDER; CLINICAL-PRACTICE GUIDELINE; FOLLOW-UP; HYPERACTIVE-CHILDREN; METHYLPHENIDATE; ADDERALL AB Objective: Assess long-term tolerability and efficacy of once-daily mixed amphetamine salts extended release (MAS XR) for attention-deficit/hyperactivity disorder (ADHD) in adolescents (13-17 years of age). Methods: Efficacy of MAS XR (10-60 mg/day) in 138 adolescents with ADHD was assessed in a 6-month, open-label, extension study following participation in a 4-week, randomized, placebo-controlled trial of MAS XR. Efficacy was based on ADHD Rating Scale-IV (ADHD-RS-IV) scores and Clinical Global Impressions-Improvement (CGI-I) ratings at end point. Tolerability was based on reported adverse events, physical and laboratory examinations, vital signs, and electrocardiographic measures. Findings: Patients exhibited sustained improvement in ADHD symptoms in this 6-month, open-label study of MAS XR 10-60 mg/day. End point ADHD-RS-IV total score was significantly decreased from baseline (- 7.9; P<.0001); similar decreases were seen for hyperactivity/impulsivity (40; P<.0001) and inattentiveness (-3.8; P<.0001). Based on CGI-I ratings, 60.9% of patients were very much/much improved, 33.3% were unchanged, 5.8% were much worse, and 0% were very much worse. The most common adverse events related to MAS XR were anorexia (24.6%), weight loss (24.6%), headache (14.5%), and nervousness (13.0%). Conclusion: Long-term MAS XR therapy is generally well tolerated and exerts sustained control of ADHD symptoms in otherwise healthy adolescents. C1 Massachusetts Gen Hosp, Pediat Psychopahrmacol Res Unit, Boston, MA 02114 USA. RP Spencer, TJ (reprint author), Massachusetts Gen Hosp, Pediat Psychopahrmacol Res Unit, 55 Fruit St,Warren 705, Boston, MA 02114 USA. EM tspencer@partners.org NR 25 TC 9 Z9 9 U1 2 U2 6 PU M B L COMMUNICATIONS, INC PI NEW YORK PA 333 HUDSON ST, 7TH FLOOR, NEW YORK, NY 10013 USA SN 1092-8529 J9 CNS SPECTRUMS JI CNS Spectr. PD OCT PY 2005 VL 10 IS 10 SU 15 BP 14 EP 21 PG 8 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 979OC UT WOS:000232953700003 PM 17151572 ER PT J AU Wilens, TE Spencer, TJ Biederman, J AF Wilens, TE Spencer, TJ Biederman, J TI Short- and long-term cardiovascular effects of mixed amphetamine salts extended-release in adolescents with ADHD SO CNS SPECTRUMS LA English DT Article ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; CLINICAL-PRACTICE GUIDELINE; DEFICIT DISORDER; BLOOD-PRESSURE; CHILDREN; METHYLPHENIDATE; MEDICATION AB Objective: Assess cardiovascular effects of once-daily mixed amphetamine salts extended release (MAS XR) in adolescents (13-17 years of age) with attention-deficit/hyperactivity disorder (ADHD). Methods: Blood pressure (BP), pulse, and electrocardiograms were assessed in 327 healthy subjects during a 4-week, randomized, double-blind, placebo-controlled, forced dose-titration study. Placebo (n=69) or once-daily MAS XR (10, 20, 30, or 40 mg) was administered to subjects <= 75 kg (n=233); 50- and 60-mg MAS XR was administered to subjects >75 kg (n=25). One hundred thirty-eight subjects participated in a 6-month, open-label extension study. Findings: Changes in BP and QTcB (Bazett's formula) intervals at 4 weeks with MAS XR were not significantly different from the placebo group. Pulse increased by 5.0 and 8.5 bpm after 3 weeks with MAS XR 20 and 50 mg/day, respectively (P <=.002). After 6 months of open-label MAS XR treatment, mean increases in systolic BP (1.7 mm Hg; P=.0252) and Pulse (4-4 bpm; P<.0001) were statistically, but not clinically, significant; diastolic BP was not significantly changed (0.6 mm Hg). A decrease in QTcB interval (-4.6 +/- 19.9 msec) was statistically (P=.009), but not clinically, significant. There were no serious cardiovascular adverse events. Conclusion: Cardiovascular effects of short- and long-term MAS XR treatment (<= 60 mg/day) were minimal in otherwise healthy adolescents with ADHD. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Wilens, TE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 15 Parkman St,WQCC 725, Boston, MA 02114 USA. EM twilens@partners.org NR 31 TC 13 Z9 13 U1 0 U2 10 PU M B L COMMUNICATIONS, INC PI NEW YORK PA 333 HUDSON ST, 7TH FLOOR, NEW YORK, NY 10013 USA SN 1092-8529 J9 CNS SPECTRUMS JI CNS Spectr. PD OCT PY 2005 VL 10 IS 10 SU 15 BP 22 EP 30 PG 9 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 979OC UT WOS:000232953700004 ER PT J AU Wu, EQ Birnbaum, EG Mareva, M Tuttle, E Castor, AR Jackman, W Ruskin, J AF Wu, EQ Birnbaum, EG Mareva, M Tuttle, E Castor, AR Jackman, W Ruskin, J TI Economic burden and co-morbidities of atrial fibrillation in a privately insured population SO CURRENT MEDICAL RESEARCH AND OPINION LA English DT Article; Proceedings Paper CT 9th Annual International Meeting of the International-Society-for-Pharmacoeconomics-and-Outcomes-Research CY MAY 16-19, 2004 CL Arlington, VA SP Int Soc Pharmacoecon & Outcomes Res DE atrial fibrillation; economic burden; medical costs; workplace costs ID UNITED-STATES; PREVENTION; MANAGEMENT; COSTS AB Objective: This study assesses the direct (medical and drugs) and indirect (work loss) annual costs associated with Atrial Fibrillation (AFIB) in a privately insured population. Background: AFIB is the most common sustained rhythm disturbance, affecting 2.3 million people in the United States. Methods: Cost and co-morbidity measures for AFIB patients were compared to matched controls using a privately insured administrative database (including medical, drug, and disability claims) for 2 million enrollees, 1999-2002 from 16 employers across the United States. Patients with an AFIB diagnosis on at least two occasions were included in the co-morbidity analysis (n = 3944). A non-AFIB control sample was randomly selected with a 1:1 ratio, with characteristics (i.e., age, gender, health plan) matched to AFIB patients. Excess medical costs (i.e., employer payments) were estimated for AFIB patients, defined as the difference in average annual costs between AFIB and control patients (n = 3944); excess work-loss costs were defined similarly for employees with available work-loss data (n = 603). Statistical significance in the descriptive analysis was measured by paired t-tests for cost, or Chi-square tests for co-morbidity comparisons. A two-part multivariate model of excess cost was further estimated to control for co-existing conditions and other patient characteristics. The excess costs of AFIB patients were estimated as the difference between the observed costs of AFIB patients and their estimated costs, assuming they did not have AFIB. Results: The multivariate analysis found that the excess annual direct cost of AFIB was $12349 (p < 0.01), with AFIB patients approximately 5 times as costly as non-AFIB individuals ($15553 versus $3204, respectively). The excess annual total cost was $14875 (p < 0.01), with AFIB patients again approximately 5 times as costly as non-AFIB individuals ($18454 versus $3579, respectively). AFIB was associated with increased incidence of atrial flutter (p < 0.01), heart failure (Relative Risk (RR) = 29, p < 0.01), other arrhythmias/conduction disorders (RR = 16, p < 0.01), heart attack (RR = 8, p < 0.01), and stroke (RR = 6, p < 0.01). Conclusions: AFIB is a costly disease and one for which more definitive therapies might offer some potential for reducing, not only the clinical impact, but also the economic burden of the disease. C1 Anal Grp Inc, Boston, MA USA. Anal Grp Inc, Menlo Pk, CA USA. Univ Oklahoma, Hlth Sci Ctr, Dept Internal Med, Oklahoma City, OK USA. Univ Oklahoma, Hlth Sci Ctr, Cardiac Arrhythmia Res Inst, Oklahoma City, OK USA. Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. RP Wu, EQ (reprint author), 111 Huntington Ave,10th Floor, Boston, MA 02119 USA. EM ewu@analysisgroup.com NR 18 TC 59 Z9 61 U1 1 U2 1 PU LIBRAPHARM PI NEWBURY PA 29-35 VENTURE WEST, NEW GREENHAM PARK, NEWBURY RG19 6HX, BERKSHIRE, ENGLAND SN 0300-7995 J9 CURR MED RES OPIN JI Curr. Med. Res. Opin. PD OCT PY 2005 VL 21 IS 10 BP 1693 EP 1699 DI 10.1185/030079905X65475 PG 7 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 976ET UT WOS:000232716300021 PM 16238910 ER PT J AU Aghi, M Rabkin, S AF Aghi, M Rabkin, S TI Viral vectors as therapeutic agents for glioblastoma SO CURRENT OPINION IN MOLECULAR THERAPEUTICS LA English DT Article DE clinical trial; gene therapy; glioblastoma; oncolytic virus; prodrug-activating enzyme; stem cells ID THYMIDINE-KINASE GENE; HUMAN-MALIGNANT GLIOMA; WILD-TYPE P53; MESENCHYMAL STEM-CELLS; PHASE-I TRIAL; BRAIN-TUMORS; RECURRENT GLIOBLASTOMA; CYTOSINE DEAMINASE; MULTIINSTITUTIONAL TRIAL; CANCER-TREATMENT AB Established treatments such as surgery, radiation and chemotherapy have not altered the median survival of glioblastoma, the most common malignant brain tumor. Since these failures reflect the highly invasive nature of glioblastoma, as well as the fact that few cells are actively replicating at any given point in time, therapies need to act in areas of the brain distant from the site of tumor origin and for long after their introduction. Over the past decade, laboratory studies and early clinical trials have raised hope that these therapeutic requirements may be fulfilled by gene therapy using non-replicating transgene-bearing viruses, oncolytic viruses or migratory stem cells to deliver tumoricidal transgenes. The principles behind these approaches and their initial results are reviewed. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Neurosurg, Mol Neurosurg Lab, Boston, MA 02114 USA. RP Aghi, M (reprint author), Massachusetts Gen Hosp, White Bldg Room 502,55 Fruit St, Boston, MA 02114 USA. EM MAGHI@PARTNERS.ORG RI rabkin, samuel/C-2443-2012 OI rabkin, samuel/0000-0003-2344-2795 NR 86 TC 20 Z9 21 U1 1 U2 1 PU CURRENT DRUGS LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1P 6LB, ENGLAND SN 1464-8431 J9 CURR OPIN MOL THER JI Curr. Opin. Mol. Ther. PD OCT PY 2005 VL 7 IS 5 BP 419 EP 430 PG 12 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 974TA UT WOS:000232613100004 PM 16248277 ER PT J AU Mrugala, MM Batchelor, TT Plotkin, SR AF Mrugala, MM Batchelor, TT Plotkin, SR TI Peripheral and cranial nerve sheath tumors SO CURRENT OPINION IN NEUROLOGY LA English DT Article DE neurofibromatosis; peripheral nerve sheath tumor; schwannoma; schwannomatosis ID VESTIBULAR SCHWANNOMAS; ACOUSTIC NEUROMA; TYPE-2 NEUROFIBROMATOSIS; CLINICAL SPECTRUM; GROWTH-RATE; RADIOSURGERY; MANAGEMENT; EXPERIENCE; MUTATIONS; EXCISION AB Purpose of review The intention of the authors is to provide the reader with an overview of the recent advances in the diagnosis and treatment of nerve sheath tumors. Vestibular schwannomas, neurogenetic syndromes such as schwannomatosis and multiple isolated neurofibromas, and malignant peripheral nerve sheath tumors are covered in this review. Recent findings Over the last year, literature focusing on different management strategies for patients with vestibular schwannomas dominated the field. Surgical options for this group of patients are changing. Stereotactic radiation is also employed more frequently with promising results. New insights into the biology of peripheral nerve tumor development and growth, including expression of vascular endothelial growth factor by vestibular schwannomas and the role of Notch signaling in malignant transformation of benign neurofibromas have been described. Diagnostic criteria for schwannomatosis, a recently described condition, are being developed. Several cases of multiple isolated neurofibromas and spinal neurofibromas were reported. Summary Peripheral nerve tumors are classified according to the specific features of cellular differentiation. The most common types include schwannoma and neurofibroma. These tumors can occur sporadically or as manifestations of genetic syndromes such as neurofibromatosis types 1 and 2 or schwannomatosis. The majority of peripheral nerve tumors are benign but malignant transformation does occur. Metastatic tumors can also affect peripheral nerves. The diagnostic modality of choice is magnetic resonance imaging. Positron emission tomography is a useful technique in the presurgical differentiation between benign and malignant peripheral nerve sheath tumors. Treatment is directed towards symptomatic control. Surgery, radiation and, in rare instances, chemotherapy are the major treatment modalities employed. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pappas Ctr Neurooncol, Boston, MA 02114 USA. RP Mrugala, MM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pappas Ctr Neurooncol, 55 Fruit St,Yawkey 9E, Boston, MA 02114 USA. EM mmrugala@partners.org NR 38 TC 39 Z9 41 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1350-7540 J9 CURR OPIN NEUROL JI Curr. Opin. Neurol. PD OCT PY 2005 VL 18 IS 5 BP 604 EP 610 DI 10.1097/01.wco.0000179507.51647.02 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 977SP UT WOS:000232823800020 PM 16155448 ER PT J AU Gupta, MA Johnson, AM Chren, MM AF Gupta, MA Johnson, AM Chren, MM TI Evaluating clinical rating scales for evidence-based dermatology: Some basic concepts SO DERMATOLOGIC CLINICS LA English DT Article ID QUALITY-OF-LIFE AB Evidence-based dermatology has necessitated the development of rating scales that measure multidimensional and abstract constructs, such as quality of life. This article discusses some basic psychometric concepts, such as reliability, validity, standardization, and measurement precision, which need to be considered when choosing a clinical rating instrument. Also discussed is the impact of these parameters on increasing the statistical power of a clinical trial. C1 Univ Western Ontario, Dept Psychiat, London, ON N6A 3K7, Canada. Univ Western Ontario, Fac Hlth Sci, London, ON N6A 3K7, Canada. Mediprobe Res Inc, London, ON, Canada. Univ Calif San Francisco, San Francisco, CA 94143 USA. San Francisco Vet Affairs Med Ctr, Hlth Serv Res Enhancement Award Program, San Francisco, CA USA. RP Gupta, MA (reprint author), 645 Windermere Rd, London, ON N5X 2P1, Canada. EM magupta@uwo.ca NR 9 TC 1 Z9 1 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0733-8635 J9 DERMATOL CLIN JI Dermatol. Clin. PD OCT PY 2005 VL 23 IS 4 BP 703 EP + DI 10.1016/j.det.2005.05.004 PG 5 WC Dermatology SC Dermatology GA 966CH UT WOS:000231996700015 PM 16112447 ER PT J AU Whitman, M Raftery, L AF Whitman, M Raftery, L TI TGF beta signaling at the summit SO DEVELOPMENT LA English DT Review AB Ligands belonging to the transforming growth factor (TGF) beta superfamily have emerged as major regulators of a wide variety of developmental events, ranging from the earliest steps in germ layer patterning of the pre-gastrula embryo to tissue healing, regeneration and homeostasis in the adult. Recently, Caroline Hill and Bob Lechleider organized the third in a bi-annual series of FASEB meetings on TGF beta signaling and development at Snowmass (CO, USA). This meeting highlighted the ongoing interplay between advances in our understanding of the molecular biology of TGF beta family signaling and in investigations into its roles in specific developmental events. C1 Harvard Univ, Sch Dent Med, Dept Dev Biol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. RP Whitman, M (reprint author), Harvard Univ, Sch Dent Med, Dept Dev Biol, Boston, MA 02115 USA. EM mwhitman@hms.harvard.edu RI Raftery, Laurel/H-1406-2012 OI Raftery, Laurel/0000-0003-4797-4163 FU NIGMS NIH HHS [R01 GM060501] NR 38 TC 10 Z9 13 U1 0 U2 1 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 4205 EP 4210 DI 10.1242/dev.02023 PG 6 WC Developmental Biology SC Developmental Biology GA 980MP UT WOS:000233022900001 PM 16155212 ER PT J AU Kenyon, KL Yang-Zhou, D Cai, CQ Tran, S Clouser, C Decene, G Ranade, S Pignoni, F AF Kenyon, KL Yang-Zhou, D Cai, CQ Tran, S Clouser, C Decene, G Ranade, S Pignoni, F TI Partner specificity is essential for proper function of the SIX-type homeodomain proteins Sine oculis and Optix during fly eye development SO DEVELOPMENTAL BIOLOGY LA English DT Article DE six-co-factors; Drl; So(Drl); So(D); dominant negative; Six3; Six6; Six1; Six2 ID DETERMINATION GENE NETWORK; DROSOPHILA EYE; VISUAL-SYSTEM; ECTOPIC EYES; EYELESS GENE; ABSENT GENE; CELL FATES; EXPRESSION; DIFFERENTIATION; MELANOGASTER AB The development of the Drosophila visual system utilizes two members of the highly conserved Six-Homeobox family of transcription factor, Sine oculis and Optix. Although in vitro studies have detected differences in DNA-binding and interactions with some co-factors, questions remain as to what extent the activity for these two transcriptional regulators is redundant or specific in vivo. In this work, we show that the So(D) mutation within the Six domain does not abolish DNA-protein interactions, but alters co-factor binding specificity to resemble that of Optix. A mutation in the same region of Optix alters its activity in vivo. We propose that the dominant mutant phenotype is primarily due to an alteration in binding properties of the Sine oculis protein and that distinct partner interactions is one important mechanism in determining significant functional differences between these highly conserved factors during eye development. (c) 2005 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. RP Pignoni, F (reprint author), Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. EM francesca_pignoni@meei.harvard.edu FU NEI NIH HHS [P30EY14104, R01 EY013167, R01 EY13167] NR 38 TC 25 Z9 25 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD OCT 1 PY 2005 VL 286 IS 1 BP 158 EP 168 DI 10.1016/j.ydbio.2005.07.017 PG 11 WC Developmental Biology SC Developmental Biology GA 974FD UT WOS:000232575800012 PM 16125693 ER PT J AU Moon, NS Frolov, MV Kwon, EJ Di Stefano, L Dimova, DK Morris, EJ Taylor-Harding, B White, K Dyson, NJ AF Moon, NS Frolov, MV Kwon, EJ Di Stefano, L Dimova, DK Morris, EJ Taylor-Harding, B White, K Dyson, NJ TI Drosophila E2F1 has context-specific pro- and antiapoptotic properties during development SO DEVELOPMENTAL CELL LA English DT Article ID CELL-CYCLE; TRANSCRIPTION FACTOR; DNA-DAMAGE; S-PHASE; INDUCED APOPTOSIS; MCL-1 PROMOTER; TARGET GENES; E2F FAMILY; PROLIFERATION; REPRESSION AB E2F transcription factors are generally believed to be positive regulators of apoptosis. In this study, we show that dE2F1 and dDP are important for the normal pattern of DNA damage-induced apoptosis in Drosophila wing discs. Unexpectedly, the role that E2F plays varies depending on the position of the cells within the disc. In irradiated wild-type discs, intervein cells show a high level of DNA damage-induced apoptosis, while cells within the D/V boundary are protected. In irradiated discs lacking E2F regulation, intervein cells are largely protected, but apoptotic cells are found at the D/V boundary. The protective effect of E2F at the D/V boundary is due to a spatially restricted role in the repression of hid. These loss-of-function experiments demonstrate that E2F cannot be classified simply as a pro- or antiapoptotic factor. Instead, the overall role of E2F in the damage response varies greatly and depends on the cellular context. C1 Massachusetts Gen Hosp, Canc Res Ctr, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. Univ Illinois, Dept Biochem & Mol Genet, Chicago, IL 60607 USA. Rutgers State Univ, Dept Mol Biol & Biochem, Piscataway, NJ 08854 USA. RP Dyson, NJ (reprint author), Massachusetts Gen Hosp, Canc Res Ctr, Charlestown, MA 02129 USA. EM dyson@helix.mgh.harvard.edu FU NCI NIH HHS [P01CA095281]; NIGMS NIH HHS [GM53203, GM55568] NR 53 TC 52 Z9 52 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 463 EP 475 DI 10.1016/j.devcel.2005.08.015 PG 13 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 974UL UT WOS:000232616800006 PM 16198289 ER PT J AU Noguchi, H Bonner-Weir, S Wei, FY Matsushita, M Matsumoto, S AF Noguchi, H Bonner-Weir, S Wei, FY Matsushita, M Matsumoto, S TI BETA2/NeuroD protein can be transduced into cells due to an arginine- and lysine-rich sequence SO DIABETES LA English DT Article ID INSULIN GENE; IN-VIVO; TRANSCRIPTIONAL ACTIVATION; NEUROD/BETA2 GENE; PDX-1 PROTEIN; DELIVERY; MICE; DIFFERENTIATION; TRAFFICKING; EXPRESSION AB BETA2/NeuroD, a basic helix-loop-helix transcription factor, is a key regulator of pancreatic islet morphogenesis and insulin gene transcription. Here we report for the first time that the BETA2/NeuroD protein can permeate several cells, including pancreatic islets, due to an arginine- and lysine-rich protein transduction domain sequence in its structure. The BETA2/NeuroD protein was transduced in a dose-dependent manner up to 1 mu mol/l. Transduced BETA2/NeuroD functions similarly to endogenous BETA2/ NeuroD: it binds to the insulin promoter and activates its expression. We also investigated the mechanism of BETA2/ NeuroD protein transduction. The BETA2/NeuroD protein penetrated cells by macropinocytosis and was released from endosomes homogeneously in cytoplasm and nuclei. These data suggest that BETA2/NeuroD protein transduction could be a safe and valuable strategy for enhancing insulin gene transcription without requiring gene transfer technology. C1 Kyoto Univ, Grad Sch Med, Dept Transplantat & Immunol, Sakyo Ku, Kyoto 6068507, Japan. Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Transplant & Cell Biol, Boston, MA USA. Okayama Univ, Grad Sch Med & Dent, Dept Physiol, Okayama, Japan. Kyoto Univ Hosp, Transplant Unit, Kyoto 606, Japan. RP Noguchi, H (reprint author), Kyoto Univ, Grad Sch Med, Dept Transplantat & Immunol, Sakyo Ku, 54 Kawahara Cho, Kyoto 6068507, Japan. EM noguchih@kuhp.kyoto-u.ac.jp NR 34 TC 82 Z9 85 U1 0 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD OCT PY 2005 VL 54 IS 10 BP 2859 EP 2866 DI 10.2337/diabetes.54.10.2859 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 969MD UT WOS:000232237400005 PM 16186386 ER PT J AU Bacci, S Ludovico, O Prudente, S Zhang, YY Di Paola, R Mangiacotti, D Rauseo, A Nolan, D Duffy, J Fini, G Salvemini, L Amico, C Vigna, C Pellegrini, F Menzaghi, C Doria, A Trischitta, V AF Bacci, S Ludovico, O Prudente, S Zhang, YY Di Paola, R Mangiacotti, D Rauseo, A Nolan, D Duffy, J Fini, G Salvemini, L Amico, C Vigna, C Pellegrini, F Menzaghi, C Doria, A Trischitta, V TI The K121Q polymorphism of the ENPP1/PC-1 gene is associated with insulin resistance/atherogenic phenotypes, including earlier onset of type 2 diabetes and myocardial infarction SO DIABETES LA English DT Article ID MEMBRANE GLYCOPROTEIN PC-1; RESISTANCE; MELLITUS; RECEPTOR; VARIANT; SUSCEPTIBILITY; PERSPECTIVES; MECHANISMS; DISEASE; GLUCOSE AB Insulin resistance (IR) is pathogenic for type 2 diabetes and coronary artery disease (CAD). The K121Q polymorphism of the ENPP1/PC-1 gene is associated with IR. Our aim was to investigate the role of the 121Q variant on the risk of type 2 diabetes and CAD. Nondiabetic control subjects (n = 638), type 2 diabetic patients without CAD (n = 535), and type 2 diabetic patients with CAD (n = 434) from Italy and the U.S. were studied. The proportion of 121Q carriers progressively increased in the three groups (27.4, 28.8, and 33.2%, respectively; adjusted P value = 0.027). Among diabetic patients (n = 969), 121Q carriers had an increased risk of developing type 2 diabetes before the age of 65 years (adjusted odds ratio [OR] 2.2 6, 95% CI 1.26-4.03; P = 0.006) and having a myocardial infarction (MI) (n = 156) by 50 years of age (3.17, 1.46-6.88, P = 0.007). The 121Q variant was also associated with an increased risk for CAD (1.47, 1.01-2.18; P = 0.049) in diabetic patients who did not smoke (n = 546). In conclusion, the ENPP1/PC-1 121Q variant is associated with a progressive deterioration of the IR-atherogenic phenotype; among diabetic individuals, it is also associated with earlier onset of type 2 diabetes and MI. C1 CSS Sci Inst, Unit Endocrinol, San Giovanni Rotondo, FG, Italy. CSS Mendel Inst, Rome, Italy. Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. CSS Sci Inst, Unit Cardiol, San Giovanni Rotondo, Italy. Consorzio Mario Negri Sud, Dept Clin Pharmacol & Epidemiol, Santa Maria Imbaro, Italy. Univ Roma La Sapienza, Dept Clin Sci, Rome, Italy. RP Bacci, S (reprint author), CSS Sci Inst, Unit Endocrinol, Viale Cappuccini 1, San Giovanni Rotondo, FG, Italy. EM dnnwba@tin.it; vincenzo.trischitta@uniroma1.it RI Di Paola, Rosa/G-7813-2011; Prudente, Sabrina/H-2886-2016; Trischitta, Vincenzo/K-1487-2016; Salvemini, Lucia/K-2121-2016; OI Di Paola, Rosa/0000-0001-5837-9111; Prudente, Sabrina/0000-0001-9220-8981; Trischitta, Vincenzo/0000-0003-1174-127X; Salvemini, Lucia/0000-0001-8776-9477; Menzaghi, Claudia/0000-0002-7438-8955 FU NHLBI NIH HHS [HL73168]; NIDDK NIH HHS [DK36836] NR 23 TC 71 Z9 77 U1 0 U2 8 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 3021 EP 3025 DI 10.2337/diabetes.54.10.3021 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 969MD UT WOS:000232237400027 PM 16186408 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 Schwartz, GG Olson, AG Szarek, M Sasiela, WJ AF Schwartz, GG Olson, AG Szarek, M Sasiela, WJ TI Relation of characteristics of metabolic syndrome to short-term prognosis and effects of intensive statin therapy after acute coronary syndrome: An analysis of the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) trial SO DIABETES CARE LA English DT Article ID DIABETES-MELLITUS; NONDIABETIC PATIENTS; INSULIN-RESISTANCE; CARDIOVASCULAR-DISEASE; CLINICAL-OUTCOMES; ARTERY-DISEASE; INFARCTION; HYPERTENSION; HISTORY; OBESITY AB OBJECTIVE - We examined relations between characteristics of the metabolic syndrome, early cardiovascular risk, and effect of early, intensive statin therapy after acute coronary syndrome. RESEARCH DESIGN AND METHODS - A total of 3,038 patients in the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) trial were characterized by the presence or absence of a history of diabetes, a history of hypertension and/or blood pressure >= 130/>= 85, BMI >30 kg/m(2), HDL cholesterol <40 mg/dl (men) or <50 mg/dl (women), and triglycerides E 150 mg/dl. Patients with three or more of these characteristics were categorized as having metabolic syndrome. RESULTS - A total of 38% of patients (n = 1, 161) met criteria for metabolic syndrome as defined in this study and had a 19% incidence of a primary end point event (death, nonfatal myocardial infarction, cardiac arrest, or recurrent unstable myocardial ischemia) during the 16-week trial. Patients with two or fewer characteristics (n = 1,877) were classified as not having metabolic syndrome and had a 14% incidence of a primary end point event. In univariate analysis, the individual characteristics that bore a significant relation to risk were diabetes and low HDL cholesterol. In a multivariable model including age, sex, and randomized treatment assignment, presence of metabolic syndrome was associated with a hazard ratio of 1.49 (95% CI 1.24-1.79, P < 0.0001). Relative risk reduction with 80 mg atorvastatin daily compared wit placebo was similar in patients with and without metabolic syndrome. CONCLUSIONS - Metabolic syndrome, as defined in the context of this clinical trial, is a strong predictor of early recurrent ischemic events after acute coronary syndrome. C1 Denver VA Med Ctr, Cardiol Sect, Denver, CO 80220 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. Linkoping Univ, Dept Internal Med, Linkoping, Sweden. Pifzer, New York, NY USA. RP Schwartz, GG (reprint author), Denver VA Med Ctr, Cardiol Sect, 111B, Denver, CO 80220 USA. EM gregory.schwartz@med.va.gov NR 30 TC 47 Z9 50 U1 0 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD OCT PY 2005 VL 28 IS 10 BP 2508 EP 2513 DI 10.2337/diacare.28.10.2508 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 971CO UT WOS:000232358900028 PM 16186288 ER PT J AU King, A Lock, J Xu, G Bonner-Weir, S Weir, GC AF King, A Lock, J Xu, G Bonner-Weir, S Weir, GC TI Islet transplantation outcomes in mice are better with fresh islets and exendin-4 treatment SO DIABETOLOGIA LA English DT Article DE diabetes; exendin-4; islet transplantation ID BETA-CELL MASS; PANCREATIC-ISLETS; INSULIN-SECRETION; DIABETIC-RATS; GROWTH; HYPERGLYCEMIA; APOPTOSIS; REVASCULARIZATION; PROLIFERATION; REPLICATION AB Aims/hypothesis: Although islet transplantation in diabetes holds great promise, two or three donor pancreases are usually required to achieve normoglycaemia in human or rodent recipients. We investigated whether there were differences between fresh and cultured islets in terms of transplantation outcome. We also investigated the effects of normoglycaemia during engraftment and the effects of exendin-4, a glucagon-like peptide-1 receptor agonist, on islet transplantation. Materials and methods: Seventy-five fresh islets were transplanted to the right kidney of diabetic mice and 425 fresh islets were transplanted to the left kidney. The mice were treated with exendin-4 or vehicle for 14 days, after which the large graft was removed by left nephrectomy. In a separate set of experiments, islets cultured in the presence or absence of exendin-4 for 72 h, or fresh islets, were transplanted to diabetic mice. In both sets of experiments, blood glucose levels were monitored. Results: Compared with cultured islets, fresh islets were more effective at reversing hyperglycaemia in mice. The treatment of the recipient mice with exendin-4 did not have beneficial effects on glucose homeostasis. However, when islets are cultured, exendin-4 treatment increases the rate of reversal of hyperglycaemia, but not to the degree of fresh islets. Conclusions/interpretation: Fresh islets are more effective than cultured islets at reversing hyperglycaemia. Exendin-4 has beneficial effects on islet transplantation. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, Boston, MA 02115 USA. RP Weir, GC (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Sect Islet Transplantat & Cell Biol, Boston, MA 02115 USA. EM gordon.weir@joslin.harvard.edu RI King, Aileen/I-5935-2013; OI King, Aileen/0000-0001-5759-7985; Bonner-Weir, Susan/0000-0003-4682-0656 FU NIDDK NIH HHS [DK 50657, P30DK36836-16, U19DK6125] NR 28 TC 55 Z9 60 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD OCT PY 2005 VL 48 IS 10 BP 2074 EP 2079 DI 10.1007/s00125-005-1922-0 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 971SN UT WOS:000232405100020 PM 16132945 ER PT J AU Halperin, F Beckman, JA Patti, ME Trujillo, ME Garvin, M Creager, MA Scherer, PE Goldfine, AB AF Halperin, F Beckman, JA Patti, ME Trujillo, ME Garvin, M Creager, MA Scherer, PE Goldfine, AB TI The role of total and high-molecular-weight complex of adiponectin in vascular function in offspring whose parents both had type 2 diabetes SO DIABETOLOGIA LA English DT Article DE adiponectin; cardiovascular disease; endothelial function; high-density lipoprotein; insulin resistance ID HIGH-DENSITY-LIPOPROTEIN; ENDOTHELIUM-DEPENDENT VASODILATION; PLASMINOGEN-ACTIVATOR INHIBITOR-1; HOMEOSTASIS MODEL ASSESSMENT; ADIPOSE-SPECIFIC PROTEIN; C-REACTIVE PROTEIN; INSULIN-RESISTANCE; PLASMA-PROTEIN; MEDIATED VASODILATION; SERUM ADIPONECTIN AB Aims/hypothesis: Adiponectin is an adipokine with insulin-sensitising and anti-atherogenic properties. We studied the role played by total adiponectin and by the bioactive high-molecular-weight (HMW) oligomeric complexes of adiponectin in vascular function in offspring whose parents both had type 2 diabetes, a population at high risk of diabetes and atherosclerosis. Methods: Total and %HMW adiponectin, the cytokines C-reactive protein, interleukin-6 and plasminogen activator inhibitor-1 (PAI-1), as well as lipid profiles were assayed in 19 offspring, each with two type 2 diabetic parents. Subjects underwent OGTTs and IVGTTs. Endothelium-dependent vasodilation (EDV) was assessed by brachial artery ultrasonography. Results: There was a significant relationship between %HMW and total adiponectin levels (r=0.72, p=0.001). Despite an expected strong positive correlation between HDL-cholesterol and adiponectin levels (r=0.52, p=0.04), as well as HDL-cholesterol and EDV (r=0.56, p < 0.02), there was no significant relationship between either total adiponectin or % HMW adiponectin and EDV. Adiponectin was inversely associated with PAI-1 (r=0.50, p=0.05), but did not correlate with the inflammatory markers C-reactive protein or interleukin-6. Conclusions/interpretation: In offspring of diabetic parents, a population at high risk of diabetes and atherosclerotic disease, there is no relationship between total or %HMW adiponectin and endothelium-dependent vasodilation. However, low adiponectin was associated with impaired fibrinolysis as manifested by increased levels of plasminogen activator inhibitor-1. C1 Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Albert Einstein Coll Med, Bronx, NY 10467 USA. RP Goldfine, AB (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM allison.goldfine@joslin.harvard.edu RI Trujillo, Martha/L-1763-2014; OI Trujillo, Martha/0000-0002-9193-1673; Beckman, Joshua/0000-0001-8332-8439 FU NCRR NIH HHS [M01 RR001032]; NHLBI NIH HHS [P01 HL48743]; NIDDK NIH HHS [K23-DK02795]; PHS HHS [R01062948] NR 62 TC 29 Z9 29 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD OCT PY 2005 VL 48 IS 10 BP 2147 EP 2154 DI 10.1007/s00125-005-1901-5 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 971SN UT WOS:000232405100029 PM 16091909 ER PT J AU DuBois, S Eng, S Bhattacharya, R Rulyak, S Hubbard, T Putnam, D Kearney, DJ AF DuBois, S Eng, S Bhattacharya, R Rulyak, S Hubbard, T Putnam, D Kearney, DJ TI Breath ammonia testing for diagnosis of hepatic encephalopathy SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE encephalopathy; cirrhosis; ammonia ID NUMBER-CONNECTION TESTS; LIVER-DISEASE; BLOOD AMMONIA AB Measurement of arterial ammonia has been used as a diagnostic test for hepatic encephalopathy, but obtaining an arterial specimen is an invasive procedure. The aim of this study was to evaluate the ability of a minimally invasive, highly sensitive optical sensing device to detect ammonia in the breath of patients with end-stage liver disease and to evaluate the correlation of breath ammonia levels, arterial ammonia levels, and psychometric testing. Fifteen subjects with liver cirrhosis and clinical evidence of hepatic encephalopathy underwent mini-mental status examination, number connection test, focused neurological examination, and arterial ammonia testing. On the same day, breath ammonia testing was performed using an apparatus that consists of a sensor (a thin membrane embedded with a pH-sensitive dye) attached to a fiberoptic apparatus that detects optical absorption. Helicobacter pylori testing was performed using the C-14 urea breath test. A positive correlation was found between arterial ammonia level and time to complete the number connection test (r = 0.31, P = 0.03). However, a negative correlation was found between breath ammonia level and number connection testing (r = -0.55, P = 0.03). Furthermore, no correlation was found between breath and arterial ammonia levels (r = -0.005, P = 0.98). There is a significant correlation between the trailmaking test and arterial ammonia levels in patients with cirrhosis. However, no correlation was found between breath and arterial ammonia levels using the fiberoptic ammonia sensor apparatus in this small study. C1 Univ Washington, Sch Med, Dept Med, Div Gastroenterol, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Primary & Specialty Med Care Serv, Seattle, WA USA. Pacific Technol, Kirkland, WA USA. RP Kearney, DJ (reprint author), Seattle VAMC, 111GI,1660 S Columbian Way, Seattle, WA 98108 USA. EM kearney@u.washington.edu NR 17 TC 43 Z9 43 U1 1 U2 19 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 1780 EP 1784 DI 10.1007/s10620-005-2937-6 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 968KS UT WOS:000232162000005 PM 16187173 ER PT J AU Sekhon, JS Chung, RT Epstein, M Kaplan, MM AF Sekhon, JS Chung, RT Epstein, M Kaplan, MM TI Steroid-responsive (autoimmune?) sclerosing cholangitis SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE sclerosing cholangitis; glucocorticoids; prednisone; bile ducts ID ULCERATIVE COLITIS; NATURAL-HISTORY; AZATHIOPRINE; THERAPY; PERICHOLANGITIS; METHOTREXATE C1 Massachusetts Gen Hosp, GI Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Tufts Univ New England Med Ctr, Div Gastroenterol, Boston, MA 02111 USA. RP Chung, RT (reprint author), Massachusetts Gen Hosp, GI Unit, GRJ 825, Boston, MA 02114 USA. EM rtchung@partners.org NR 17 TC 5 Z9 5 U1 0 U2 2 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 1839 EP 1843 DI 10.1007/s10620-005-2948-3 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 968KS UT WOS:000232162000016 PM 16187184 ER PT J AU Goss, P Ingle, J Dongsheng, T AF Goss, P. Ingle, J. Dongsheng, T. CA MA17 Collaborat Trialists NCIC TI Oral NCICCTG MA17: Disease free survival according to estrogen receptor and progesterone receptor status of the primary tumor SO EJC SUPPLEMENTS LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. Mayo Clin, Rochester, MN USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD OCT PY 2005 VL 3 IS 2 SU S BP 74 EP 75 PG 2 WC Oncology SC Oncology GA 183HV UT WOS:000247564800247 ER PT J AU Ingi, J Goss, P Dongsheng, T AF Ingi, J. Goss, P. Dongsheng, T. TI NCICCTG MAI 7: Increasing benefit of letrozole with longer duration of treatment as measured by the hazard ratio of disease recurrence over time SO EJC SUPPLEMENTS LA English DT Meeting Abstract C1 Mayo Clin, Rochester, MN USA. Massachusetts Gen Hosp, Boston, MA 02114 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 74 EP 74 PG 1 WC Oncology SC Oncology GA 183HV UT WOS:000247564800246 ER PT J AU Miller, K Wang, M Gralow, J Dickler, M Cobleigh, MA Perez, EA Shenkier, TN Davidson, NE AF Miller, K. Wang, M. Gralow, J. Dickler, M. Cobleigh, M. A. Perez, E. A. Shenkier, T. N. Davidson, N. E. TI First-line bevacizumab and paclitaxel in patients with locally recurrent or metastatic breast cancer: a randomized, phase III trial coordinated by the Eastern Cooperative Oncology Group (E2100) SO EJC SUPPLEMENTS LA English DT Meeting Abstract C1 Indiana Univ, Ctr Canc, Indianapolis, IN 46204 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Puget Sound Oncol Consortium, Seattle, WA USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Rush Univ, Med Ctr, Chicago, IL 60612 USA. Mayo Clin, Jacksonville, FL 32224 USA. Vancouver Canc Ctr, British Columbia Canc Agcy, Vancouver, BC, Canada. Johns Hopkins Univ, Sch Med, Johns Hopkins Oncol Ctr, Baltimore, MD 21205 USA. NR 0 TC 11 Z9 11 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 77 EP 78 PG 2 WC Oncology SC Oncology GA 183HV UT WOS:000247564800255 ER PT J AU Miller, KD Burstein, HJ Elias, AD Rugo, HS Cobleigh, MA Wolff, AC Eisenberg, RD Collier, M Adams, BJ Baum, CM AF Miller, K. D. Burstein, H. J. Elias, A. D. Rugo, H. S. Cobleigh, M. A. Wolff, A. C. Eisenberg, R. D. Collier, M. Adams, B. J. Baum, C. M. TI Safety and efficacy of sunitinib malate (SU11248) as second-line therapy in metastatic breast cancer (MIBC) patients: preliminary results from a Phase II study SO EJC SUPPLEMENTS LA English DT Meeting Abstract C1 Indiana Univ, Indianapolis, IN 46204 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. Johns Hopkins Univ, Sidney Kimmel Canc Ctr, Baltimore, MD 21218 USA. Calif Canc Ctr Inc, Los Angeles, CA USA. Pfizer Inc, La Jolla, CA USA. NR 0 TC 8 Z9 8 U1 1 U2 2 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 113 EP 114 PG 2 WC Oncology SC Oncology GA 183HV UT WOS:000247564800386 ER PT J AU Lipton, A Hei, Y Coleman, R Major, P Smith, M Cook, R AF Lipton, A. Hei, Y. Coleman, R. Major, P. Smith, M. Cook, R. TI Breast cancer patients with persistently increased bone resorption SO EJC SUPPLEMENTS LA English DT Meeting Abstract C1 Milton S Hershey Med Ctr, Hershey, PA USA. Novartis Oncol, E Hanover, NJ USA. Univ Sheffield, Sheffield, S Yorkshire, England. Hamilton Reg Canc Ctr, Hamilton, ON L8V 1C3, Canada. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Waterloo, Waterloo, ON N2L 3G1, Canada. NR 0 TC 0 Z9 0 U1 0 U2 2 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 121 EP 121 PG 1 WC Oncology SC Oncology GA 183HV UT WOS:000247564800411 ER PT J AU Van den Abbeele, AD Melenevsky, Y de Vries, D Manola, J Dileo, P Tetrault, R Baum, C Badawi, RD Demetri, G AF Van den Abbeele, A. D. Melenevsky, Y. de Vries, D. Manola, J. Dileo, P. Tetrault, R. Baum, C. Badawi, R. D. Demetri, G. TI FIDG-PET imaging demonstrates kinase target inhibition by sunitinib malate (SU11248) in GIST patients resistant to or intolerant of imatinib mesylate SO EJC SUPPLEMENTS LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Pfizer Inc, La Jolla, CA USA. Univ Calif Davis, Med Ctr, Sacramento, CA 95817 USA. NR 0 TC 5 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 202 EP 203 PG 2 WC Oncology SC Oncology GA 183HV UT WOS:000247564800691 ER PT J AU Davis, DW Heymach, JV McConkey, DJ Desai, J George, S Jackson, J Bello, CD Baum, C Shalinsky, DR Demetri, GD AF Davis, D. W. Heymach, J. V. McConkey, D. J. Desai, J. George, S. Jackson, J. Bello, C. D. Baum, C. Shalinsky, D. R. Demetri, G. D. TI Receptor tyrosine kinase activity and apoptosis in gastrointestinal stromal tumours: a pharmacodynamic analysis of response to sunitinib malate (SU11248) therapy SO EJC SUPPLEMENTS LA English DT Meeting Abstract C1 Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Pfizer Inc, La Jolla, CA USA. NR 0 TC 4 Z9 4 U1 0 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 203 EP 203 PG 1 WC Oncology SC Oncology GA 183HV UT WOS:000247564800692 ER PT J AU Demetri, G van Oosterom, A Garrett, C Blackstein, M Shah, M Werweij, J McArthur, G Judson, I Baum, C Casali, P AF Demetri, G. van Oosterom, A. Garrett, C. Blackstein, M. Shah, M. Werweij, J. McArthur, G. Judson, I. Baum, C. Casali, P. TI Sunitinib malate (SU11248) prolongs progression-free and overall survival for GIST patients after failure of imatinib mesylate therapy: update of a phase III trial SO EJC SUPPLEMENTS LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. UZ Gasthuisberg, Louvain, Belgium. H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. Univ Toronto, Mt Sinai Hosp, Toronto, ON M5G 1X5, Canada. Ohio State Univ, Columbus, OH 43210 USA. Erasmus MC, Rotterdam, Netherlands. Peter MacCallum Canc Ctr, Melbourne, Australia. Royal Marsden Hosp, Sutton, Surrey, England. Pfizer Inc, La Jolla, CA USA. Ist Nazl Tumori, I-20133 Milan, Italy. NR 0 TC 4 Z9 4 U1 0 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 203 EP 203 PG 1 WC Oncology SC Oncology GA 183HV UT WOS:000247564800693 ER PT J AU Kulka, M Lenz, H Meropol, N Posey, J Picus, J Ryan, D Bergsland, E Stuart, K Baum, C Fuchs, C AF Kulka, M. Lenz, H. Meropol, N. Posey, J. Picus, J. Ryan, D. Bergsland, E. Stuart, K. Baum, C. Fuchs, C. TI Results of a phase II study with sunitinilb malate (SU11248) in patients (pts) with advanced neuroendocrine tumours (NETs) SO EJC SUPPLEMENTS LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Calif Los Angeles, Norris Comprehens Canc Ctr, Los Angeles, CA USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Univ Alabama, Birmingham, AL USA. Washington Univ, St Louis, France. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Calif San Francisco, Ctr Comprehens Canc, San Francisco, CA 94143 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Pfizer Inc, La Jolla, CA USA. NR 0 TC 9 Z9 9 U1 0 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 204 EP 204 PG 1 WC Oncology SC Oncology GA 183HV UT WOS:000247564800695 ER PT J AU Motzer, R Rini, B Michaelson, M Redman, B Hudes, G Wilding, I Bukowski, R George, D Kim, S Baum, C AF Motzer, R. Rini, B. Michaelson, M. Redman, B. Hudes, G. Wilding, I. Bukowski, R. George, D. Kim, S. Baum, C. TI Sunitinib malate (SU11248) shows antitumour activity in patients with metastatic renal cell carcinoma: updated results from phase II trials SO EJC SUPPLEMENTS LA English DT Meeting Abstract C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Univ Wisconsin, Madison, WI USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Duke Univ, Durham, NC USA. Pfizer Inc, San Diego, CA USA. NR 0 TC 6 Z9 6 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 227 EP 227 PG 1 WC Oncology SC Oncology GA 183HV UT WOS:000247564800774 ER PT J AU Oh, WK Proctor, K Nakabayashi, M Evan, C Tormey, LK Breierova, L Smith, M Neary, M AF Oh, W. K. Proctor, K. Nakabayashi, M. Evan, C. Tormey, L. K. Breierova, L. Smith, M. Neary, M. TI Risk and risk factors of renal impairment in hormone refractory prostate cancer (HPRC) patients with bone metastases (BM) treated with Zoledronic Acid (ZA) SO EJC SUPPLEMENTS LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Anal Grp Inc, Boston, MA USA. F Hoffmann La Roche & Co Ltd, CH-4002 Basel, Switzerland. RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 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 231 EP 232 PG 2 WC Oncology SC Oncology GA 183HV UT WOS:000247564800787 ER PT J AU Gordon, MS Matel, D Aghajanian, C Matulonis, U Brewer, M Fleming, G Hainsworth, J Garcia, AA Pegram, M Karlan, B AF Gordon, M. S. Matel, D. Aghajanian, C. Matulonis, U. Brewer, M. Fleming, G. Hainsworth, J. Garcia, A. A. Pegram, M. Karlan, B. TI Clinical activity of single agent pertuzumab (rhuMab 2C4), a HER dimerization inhibitor, in advanced ovarian cancer (OC): potential predictive relationship with tumor HER2 activation status SO EJC SUPPLEMENTS LA English DT Meeting Abstract C1 Arizona Canc Ctr, Scottsdale, AZ USA. Indiana Univ, Indianapolis, IN 46204 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Arizona Canc Ctr, Tucson, AZ USA. Univ Chicago, Chicago, IL 60637 USA. Sara Cannon Canc Ctr, Nashville, TN USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. UCLA Med Ctr, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD OCT PY 2005 VL 3 IS 2 SU S BP 259 EP 260 PG 2 WC Oncology SC Oncology GA 183HV UT WOS:000247564801059 ER PT J AU Ozsahin, M Oiszyk, O Karakoyun-Celik, O Pehlivan, B Azria, D Roelandts, M Kaanders, H Cengiz, M Krengli, M Zouhair, A AF Ozsahin, M. Oiszyk, O. Karakoyun-Celik, O. Pehlivan, B. Azria, D. Roelandts, M. Kaanders, H. Cengiz, M. Krengli, M. Zouhair, A. TI Outcome and prognostic factors in olfactory neuroblastoma: a multicenter rare cancer network study SO EJC SUPPLEMENTS LA English DT Meeting Abstract C1 CHU Vaudois, CH-1011 Lausanne, Switzerland. Ctr Oscar Lambret, F-59020 Lille, France. Massachusetts Gen Hosp, Boston, MA 02114 USA. Inst Gustave Roussy, Villejuif, France. CRL Val Aurelle, Montpellier, France. Inst Jules Bordet, B-1000 Brussels, Belgium. UMC St Radboud, Nijmegen, Netherlands. Univ Hacettepe, Sch Med, TR-06100 Ankara, Turkey. Univ Degli Stud Del Piemonte Orientale, Novara, Italy. 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 301 EP 302 PG 2 WC Oncology SC Oncology GA 183HV UT WOS:000247564801201 ER PT J AU Jackman, D Lucca, J Fidias, P Rabin, MS Lynch, TJ Ostler, P Skarin, AT Temel, J Johnson, BE Janne, PA AF Jackman, D. Lucca, J. Fidias, P. Rabin, M. S. Lynch, T. J. Ostler, P. Skarin, A. T. Temel, J. Johnson, B. E. Janne, P. A. TI Phase II study of the EGFR tyrosine kinase inhibitor erlotinib in patients > 70 years of age with previously untreated advanced non-small cell lung carcinoma SO EJC SUPPLEMENTS LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD OCT PY 2005 VL 3 IS 2 SU S BP 325 EP 326 PG 2 WC Oncology SC Oncology GA 183HV UT WOS:000247564801283 ER PT J AU Thatcher, N AF Thatcher, N. TI Symptom relief in patients with non-small cell lung cancer (NSCLC) after treatment with paclitaxel poliglumex (PPX, XYOTAX(TM)): phase III trial results SO EJC SUPPLEMENTS LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 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 325 EP 325 PG 1 WC Oncology SC Oncology GA 183HV UT WOS:000247564801282 ER PT J AU DePrimo, S Bello, C Smeraglia, J Shalinsky, D Freddo, J Baum, C Rini, R Michaelson, M Motzer, R Spinella, D AF DePrimo, S. Bello, C. Smeraglia, J. Shalinsky, D. Freddo, J. Baum, C. Rini, R. Michaelson, M. Motzer, R. Spinella, D. TI The multitargeted kinase inhibitor sunitinib malate (SU11248): soluble protein biomarkers of pharmacodynamic activity in patients with metastatic renal cell cancer SO EJC SUPPLEMENTS LA English DT Meeting Abstract C1 Pfizer Global R&D, La Jolla, CA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NR 0 TC 3 Z9 3 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 420 EP 420 PG 1 WC Oncology SC Oncology GA 183HV UT WOS:000247564801604 ER PT J AU Morgan, JA Demetri, GD Fletcher, JA George, S Desai, J Maki, RG Fletcher, CD Scheu, K Baum, C Heinrich, MC AF Morgan, J. A. Demetri, G. D. Fletcher, J. A. George, S. Desai, J. Maki, R. G. Fletcher, C. D. Scheu, K. Baum, C. Heinrich, M. C. TI Patients with imatinib mesylate-resistant GIST exhibit durable responses to sunitinib malate (SU11248) SO EJC SUPPLEMENTS LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Ctr Bone & Soft Tissue Oncol, Boston, MA 02115 USA. Mem Hosp, New York, NY USA. Pfizer Inc, La Jolla, CA USA. Oregon Hlth & Sci Univ, Inst Canc, Portland, OR 97201 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 421 EP 421 PG 1 WC Oncology SC Oncology GA 183HV UT WOS:000247564801608 ER PT J AU Norden-Zfoni, A Manola, J Desai, J Morgan, J Bello, C DePrimo, S Shalinsky, D Baum, C Demetri, G Heymach, J AF Norden-Zfoni, A. Manola, J. Desai, J. Morgan, J. Bello, C. DePrimo, S. Shalinsky, D. Baum, C. Demetri, G. Heymach, J. TI Circulating endothelial cells and monocytes as markers of sunitinib malate (SU11248) activity in patients with imatinib mesylate-resistant GIST SO EJC SUPPLEMENTS LA English DT Meeting Abstract C1 Childrens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Pfizer Global R&D, La Jolla, CA USA. NR 0 TC 2 Z9 2 U1 0 U2 2 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 423 EP 423 PG 1 WC Oncology SC Oncology GA 183HV UT WOS:000247564801613 ER PT J AU Myers, MG Patti, ME Leshan, RL AF Myers, MG Patti, ME Leshan, RL TI Hitting the target: Leptin and perinatal nutrition in the predisposition to obesity SO ENDOCRINOLOGY LA English DT Editorial Material ID BIRTH-WEIGHT; LATER LIFE; EXPOSURE; FAMINE; FETAL; SURGE; MICE C1 Univ Michigan, Div Endocrinol Diabet & Metab, Dept Internal Med, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. RP Myers, MG (reprint author), Univ Michigan, Div Endocrinol Diabet & Metab, Dept Internal Med, 1150 W Med Ctr Dr,4301 MSRB 3,Box 0638, Ann Arbor, MI 48109 USA. NR 21 TC 6 Z9 6 U1 0 U2 0 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 4209 EP 4210 DI 10.1210/en.2005-0971 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 964QR UT WOS:000231896100009 PM 16166232 ER PT J AU Stefan, M Ji, H Simmons, RA Cummings, DE Ahima, RS Friedman, MI Nicholls, RD AF Stefan, M Ji, H Simmons, RA Cummings, DE Ahima, RS Friedman, MI Nicholls, RD TI Hormonal and metabolic defects in a Prader-Willi syndrome mouse model with neonatal failure to thrive SO ENDOCRINOLOGY LA English DT Article ID FACTOR BINDING PROTEIN-1; GROWTH-HORMONE; BODY-COMPOSITION; POSTNATAL LETHALITY; ANGELMAN-SYNDROMES; RAT HEPATOCYTES; ENERGY-BALANCE; GHRELIN LEVELS; FOOD-INTAKE; IGF-I AB Prader-Willi syndrome (PWS) has a biphasic clinical phenotype with failure to thrive in the neonatal period followed by hyperphagia and severe obesity commencing in childhood among other endocrinological and neurobehavioral abnormalities. The syndrome results from loss of function of several clustered, paternally expressed genes in chromosome 15q11q13. PWS is assumed to result from a hypothalamic defect, but the pathophysiological basis of the disorder is unknown. We hypothesize that a fetal developmental abnormality in PWS leads to the neonatal phenotype, whereas the adult phenotype results from a failure in compensatory mechanisms. To address this hypothesis and better characterize the neonatal failure to thrive phenotype during postnatal life, we studied a transgenic deletion PWS (TgPWS) mouse model that shares similarities with the first stage of the human syndrome. TgPWS mice have fetal and neonatal growth retardation associated with profoundly reduced insulin and glucagon levels. Consistent with growth retardation, TgPWS mice have deregulated liver expression of IGF system components, as revealed by quantitative gene expression studies. Lethality in TgPWS mice appears to result from severe hypoglycemia after postnatal d 2 after depletion of liver glycogen stores. Consistent with hypoglycemia, TgPWS mice appear to have increased fat oxidation. Ghrelin levels increase in TgPWS reciprocally with the falling glucose levels, suggesting that the rise in ghrelin reported in PWS patients may be secondary to a perceived energy deficiency. Together, the data reveal defects in endocrine pancreatic function as well as glucose and hepatic energy metabolism that may underlie the neonatal phenotype of PWS. C1 Childrens Hosp Pittsburgh, Dept Pediat, Birth Defects Labs, Rangos Res Ctr, Pittsburgh, PA 15213 USA. Univ Penn, Sch Med, Dept Psychiat, Ctr Neurobiol & Behav, Philadelphia, PA 19104 USA. Monell Chem Senses Ctr, Philadelphia, PA 19104 USA. Univ Penn, Dept Med, Div Endocrinol Diabet & Metab, Sch Med, Philadelphia, PA 19104 USA. Univ Penn, Dept Genet, Sch Med, Philadelphia, PA 19104 USA. Univ Washington, Dept Med, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. RP Nicholls, RD (reprint author), Childrens Hosp Pittsburgh, Dept Pediat, Birth Defects Labs, Rangos Res Ctr, 3460 5th Ave,Room 2109, Pittsburgh, PA 15213 USA. EM robert.nicholls@chp.edu FU NIA NIH HHS [AG20898]; NICHD NIH HHS [HD36079, HD31491]; NIDDK NIH HHS [DK19525, DK49210, DK53109, DK55704, DK61516] NR 59 TC 30 Z9 30 U1 1 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 4377 EP 4385 DI 10.1210/en.2005-0371 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 964QR UT WOS:000231896100028 PM 16002520 ER PT J AU Sharma, VK Eliakim, R Sharma, P Faigel, D AF Sharma, VK Eliakim, R Sharma, P Faigel, D TI ICCE consensus for esophageal capsule endoscopy SO ENDOSCOPY LA English DT Article; Proceedings Paper CT 4th International Conference on Capsule Endoscopy CY MAR 07-09, 2005 CL Miami Beach, FL ID BARRETTS-ESOPHAGUS; UNITED-STATES; ADENOCARCINOMA; DISEASES C1 Mayo Clin Scottsdale, Dept Internal Med, Div Gastroenterol & Hepatol, Scottsdale, AZ 85259 USA. Technion Israel Inst Technol, Rambam Med Ctr, Dept Gastroenterol, Haifa, Israel. Univ Kansas, Sch Med, Div Gastroenterol Hepatol & Nutr, Kansas City, MO USA. VA Med Ctr, Kansas City, MO USA. Oregon Hlth Sci Univ, Portland VA Med Ctr, Dept Med, Portland, OR 97201 USA. RP Sharma, VK (reprint author), Mayo Clin Scottsdale, Div Gastroenterol, 13400 E Shea Blvd, Scottsdale, AZ 85259 USA. EM sharma.virender@mayo.edu NR 17 TC 22 Z9 25 U1 0 U2 0 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0013-726X J9 ENDOSCOPY JI Endoscopy PD OCT PY 2005 VL 37 IS 10 BP 1060 EP 1064 DI 10.1055/s-870311 PG 5 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 974HC UT WOS:000232581000029 PM 16189791 ER PT J AU Ku, CH Liu, YT Christiani, DC AF Ku, CH Liu, YT Christiani, DC TI Case report: Occupationally related recurrent varicella (chickenpox) in a hospital nurse SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE chickenpox; indirect fluroscent antibody; occupational exposure; polymerase chain reaction; shingles; Taiwan; varicella-zoster virus ID ZOSTER-VIRUS-DNA; INFECTION; SPREAD; GE AB Commonly accepted outcomes of varicella-zoster virus (VZV) infections include chickenpox (primary) and shingles (recurrence or latency), as well lifetime immunity against chickenpox. We report the case of a registered nurse who worked in a neurologic surgery ward in a general hospital in Taipei, Taiwan. While working there for approximately 1 year, she developed recurrent chickenpox after caring for a paraparesis patient, who had herpes zoster during hospitalization in August 2002. The varicella incubation period was 10 days, which matched the range (10-21 days). Recently negative specific serum IgM and positive specific serum IgG indicated a past VZV infection. The nurse did not get herpes zoster from the second episode of varicella on 9 August 2002 to 4 April 2005 and is now convalescing. We conclude that occupational VZV hazards exist in the health care environment and suggest testing for VZV antibody and a VZV vaccination program for susceptible health care workers. C1 Natl Def Univ, Natl Def Med Ctr, Sch Publ Hlth, Taipei 114, Taiwan. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth & Epidemiol, Boston, MA 02115 USA. Natl Def Univ, Natl Def Med Ctr, Dept Microbiol & Immunol, Taipei, Taiwan. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. RP Ku, CH (reprint author), Natl Def Univ, Natl Def Med Ctr, Sch Publ Hlth, Room 4328,161,Sect 6,Min Chuan E Rd, Taipei 114, Taiwan. EM cku@mail.ndmctsgh.edu.tw NR 20 TC 6 Z9 6 U1 0 U2 1 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD OCT PY 2005 VL 113 IS 10 BP 1373 EP 1375 DI 10.1289/ehp.7766 PG 3 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 970GF UT WOS:000232292600044 PM 16203249 ER PT J AU Kossoff, EH Thiele, EA Pfeifer, HH McGrogan, JR Freeman, JM AF Kossoff, EH Thiele, EA Pfeifer, HH McGrogan, JR Freeman, JM TI Tuberous sclerosis complex and the ketogenic diet SO EPILEPSIA LA English DT Article DE tuberous sclerosis complex; epilepsy; ketogenic diet ID INFANTILE SPASMS; EPILEPSY SURGERY; VIGABATRIN; CHILDREN; IDENTIFICATION; EFFICACY; GENE AB Purpose: Tuberous sclerosis complex (TSC) is a condition that is frequently associated with intractable, early-onset epilepsy, and often is first seen as infantile spasms. If medications fail and no clear epileptogenic tuber is identified, nonpharmacologic therapies are often attempted. The use of the ketogenic diet specifically for children with TSC and epilepsy has not been previously described. Methods: A chart review was performed of patients with TSC treated with the ketogenic diet over a 5-year period at Johns Hopkins Hospital and Massachusetts General Hospital. Results: Twelve children, ages 8 months to 18 years, were identified. Eleven (92%) children had a > 50% reduction in their seizures at 6 months on the diet, and 8 (67%) had a > 90% response. Five children had at least a 5-month seizure-free response. Diet duration ranged from 2 months to 5 years (mean, 2 years). Conclusions: In this limited-duration case series of 12 patients, the ketogenic diet was a generally effective therapeutic modality for the intractable epilepsy occasionally seen in children with TSC. C1 Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA. Johns Hopkins Univ, John M Freeman Pediat Epilepsy Ctr, Dept Pediat, Baltimore, MD 21218 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pediat Epilepsy Program, Boston, MA 02115 USA. RP Kossoff, EH (reprint author), Johns Hopkins Univ Hosp, 600 N Wolfe St,Jefferson 128, Baltimore, MD 21287 USA. EM ekossoff@jhmi.edu FU NCRR NIH HHS [M01-RR00052] NR 14 TC 68 Z9 73 U1 1 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD OCT PY 2005 VL 46 IS 10 BP 1684 EP 1686 DI 10.1111/j.1528-1167.2005.00266.x PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 966FP UT WOS:000232005800018 PM 16190943 ER PT J AU Boehm, JS Hahn, WC AF Boehm, JS Hahn, WC TI Cancer genetics - Finding the right mix SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Editorial Material ID TISSUE; CELLS C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol & Med, Boston, MA 02115 USA. MIT, Cambridge, MA 02139 USA. Harvard Univ, Broad Inst, Cambridge, MA 02139 USA. RP Boehm, JS (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St,Dana 710C, Boston, MA 02115 USA. EM William_Hahn@dfci.harvard.edu OI Boehm, Jesse/0000-0002-6795-6336 NR 8 TC 2 Z9 2 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1018-4813 J9 EUR J HUM GENET JI Eur. J. Hum. Genet. PD OCT PY 2005 VL 13 IS 10 BP 1099 EP 1100 DI 10.1038/sj.ejhg.5201477 PG 2 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 968FG UT WOS:000232146700001 PM 16077731 ER PT J AU Solomon, S Rajasekaran, N Jeisy-Walder, E Snapper, SB Illges, H AF Solomon, S Rajasekaran, N Jeisy-Walder, E Snapper, SB Illges, H TI A crucial role for macrophages in the pathology of K/B x N serum-induced arthritis SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE macrophages; mast cells; CD40; arthritis ID WISKOTT-ALDRICH-SYNDROME; ANTIBODY-INDUCED ARTHRITIS; TUMOR-NECROSIS-FACTOR; RHEUMATOID-ARTHRITIS; SYNDROME PROTEIN; INFLAMMATORY ARTHRITIS; AUTOIMMUNE-DISEASE; PASSIVE TRANSFER; CELL ACTIVATION; CUTTING EDGE AB Autoantibodies in the form of immune complexes are known to be crucial mediators in initiating inflammation in a variety of autoimmune diseases. This has been well documented in the anti-collagen II antibody-induced arthritis animal model for a long time now. Recently, in the K/B x N mouse model (the F1 of the TCR-transgenic KRN and the diabetic NOD mice), anti-glucose-6-phosphate isomerase (GPI) autoantibodies have been shown to induce arthritis. Experimental work in the K/B x N model demonstrated key roles of autoantigenic immune complexes activating the alternative pathway of complement, the subsequent association with C5aR and Fc gamma RIII-mediated cell activation and production of the inflammatory cytokines IL-1 and TNF-alpha,, finally leading to joint destruction. The presence of high amounts of inflammatory cytokines and matrix-degrading proteases at sites of inflammation obviously put the cytokine-producing macrophages as the next target for investigation in this model. Here, we show that mice depleted of macrophages by clodronate liposome treatment are completely resistant to K/B x N serum-induced arthritis. Reconstituting clodronate liposome-treated mice with macrophages from naive animals could reverse this resistance. Also, we found that deficiencies in the Wiskott-Aldrich syndrome protein and CD40, which are both implicated in macrophage activation, chemotaxis and phagocytosis, are not essential in serum-induced arthritis. Mast cell degranulation was seen in arthritogenic serum-treated mice even in the absence of macrophages, possibly suggesting that mast cell degranulation/activation acts hierarchically before macrophages in the inflammatory cascade of anti-GPI antibody-induced arthritis. C1 Univ Appl Sci, Dept Nat Sci Immunol & Cell Biol, D-53359 Rheinbach, Germany. Univ Konstanz, Fac Sci, Dept Biol, D-7750 Constance, Germany. Biotechnol Inst Thurgau, Tagerwilen, Switzerland. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Illges, H (reprint author), Univ Appl Sci, Dept Nat Sci Immunol & Cell Biol, Bonn Rhein Sieg Von Liebig Str 20, D-53359 Rheinbach, Germany. EM harald.illges@fh-brs.de NR 45 TC 83 Z9 84 U1 1 U2 2 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 3064 EP 3073 DI 10.1002/eji.200526167 PG 10 WC Immunology SC Immunology GA 976SE UT WOS:000232752800029 PM 16180250 ER PT J AU Zeck, GM Xiao, Q Masland, RH AF Zeck, GM Xiao, Q Masland, RH TI The spatial filtering properties of local edge detectors and brisk-sustained retinal ganglion cells SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE ganglion; local edge detector; retina ID AMACRINE CELLS; RABBIT RETINA; RECEPTIVE-FIELDS; MAMMALIAN RETINA; NATURAL IMAGES; VISUAL-CORTEX; MOUSE RETINA; POPULATION; DIVERSITY; CODE AB We compared image computation in the rabbit retina by two different cell types: the so-called 'local edge detecting' ganglion cells and the well-known brisk-sustained ganglion cells. From both anatomical and physiological evidence, these cells are present in nearly equal numbers and thus overlap to sample the same regions of visual space. We recorded simultaneously from overlapping cells on a dense microelectrode array. The results were analysed using an anatomically realistic simulation of the retina's processing levels. The 'local edge detecting' cell was found to be tuned to higher spatial frequencies and to have a narrower spatial frequency bandpass than the brisk-sustained cells. Simulation revealed that this is due primarily to the 'zero-crossing' detector implied by the definition of the local edge detector. The outputs of the simulations in response to complex images were analysed quantitatively. The results showed the population of local edge detectors to transmit a sparser code than the brisk-sustained cells. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst, Boston, MA 02114 USA. RP Masland, RH (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst, 50 Blossom St,Wellman 429, Boston, MA 02114 USA. EM richard_masland@hms.harvard.edu RI Zeck, Gunther/H-7419-2013; OI Zeck, Gunther/0000-0003-3998-9883 NR 40 TC 29 Z9 29 U1 0 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD OCT PY 2005 VL 22 IS 8 BP 2016 EP 2026 DI 10.1111/j.1460-9568.2005.04390.x PG 11 WC Neurosciences SC Neurosciences & Neurology GA 976ZN UT WOS:000232772300018 PM 16262640 ER PT J AU Guzman-Marin, R Suntsova, N Methippara, M Greiffenstein, R Szymusiak, R McGinty, D AF Guzman-Marin, R Suntsova, N Methippara, M Greiffenstein, R Szymusiak, R McGinty, D TI Sleep deprivation suppresses neurogenesis in the adult hippocampus of rats SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE BrdU; dentate gyrus; hippocampus; neurogenesis; plasticity; sleep deprivation ID CEREBRAL PROTEIN-SYNTHESIS; GENERATED GRANULE CELLS; DENTATE GYRUS; AXONAL PROJECTIONS; STRESS; PROLIFERATION; EXPRESSION; INCREASES; NEURONS; DOUBLECORTIN AB We reported previously that 96 h of sleep deprivation (SD) reduced cell proliferation in the dentate gyrus (DG) of the hippocampus in adult rats. We now report that SD reduces the number of new cells expressing a mature neuronal marker, neuronal nuclear antigen (NeuN). Rats were sleep-deprived for 96 h, using an intermittent treadmill system. Total sleep time was reduced to 6.9% by this method in SD animals, but total treadmill movement was equated in SD and treadmill control (CT) groups. Rats were allowed to survive for 3 weeks after 5-bromo-2-deoxyuridine (BrdU) injection. The phenotype of BrdU-positive cells in the DG was assessed by immunofluorescence and confocal microscopy. After 3 weeks the number of BrdU-positive cells was reduced by 39.6% in the SD group compared with the CT. The percentage of cells that co-localized BrdU and NeuN was also lower in the SD group (SD: 46.6 +/- 1.8% vs. CT: 71.9 +/- 2.1, P < 0.001). The percentages of BrdU-labeled cells co-expressing markers of immature neuronal (DCX) or glial (S100-beta) cells were not different in SD and CT groups. Thus, SD reduces neurogenesis in the DG by affecting both total proliferation and the percentage of cells expressing a mature neuronal phenotype. We hypothesize that sleep provides anabolic or signaling support for proliferation and cell fate determination. C1 VA Greater Los Angeles Healthcare Syst, Res Serv, North Hills, CA 91343 USA. Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90024 USA. Rostov State Univ, AB Kogan Res Inst Neurocybernet, Rostov Na Donu 344006, Russia. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. RP McGinty, D (reprint author), VA Greater Los Angeles Healthcare Syst, Res Serv, North Hills, CA 91343 USA. EM dmcginty@ucla.edu FU NHLBI NIH HHS [HL 60296]; PHS HHS [47480] NR 51 TC 94 Z9 97 U1 0 U2 6 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD OCT PY 2005 VL 22 IS 8 BP 2111 EP 2116 DI 10.1111/j.1460-9568.2005.04376.x PG 6 WC Neurosciences SC Neurosciences & Neurology GA 976ZN UT WOS:000232772300027 PM 16262649 ER PT J AU Biederman, J Mick, E Surman, C Doyle, R Hammerness, P Harpold, T Dunkel, S Dougherty, M Aleardi, M Spencer, T AF Biederman, J Mick, E Surman, C Doyle, R Hammerness, P Harpold, T Dunkel, S Dougherty, M Aleardi, M Spencer, T TI A randomized, double-blind, placebo-controlled study of OROS methylphenidate in the treatment of adults with attention-deficit/hyperactivity disorder SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 18th ECNP Congress 2005 CY OCT 22-26, 2005 CL Amsterdam, NETHERLANDS SP ECNP C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 1 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 S631 EP S632 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 992CA UT WOS:000233860601326 ER PT J AU Biederman, J Doyle, A AF Biederman, J Doyle, A TI Neuropsychological functioning in youth with bipolar disorder SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 18th ECNP Congress 2005 CY OCT 22-26, 2005 CL Amsterdam, NETHERLANDS SP ECNP C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 1 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 S607 EP S607 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 992CA UT WOS:000233860601268 ER PT J AU Biederman, J Mick, E Wozniak, J Harpold, T Aleardi, M Dougherty, M AF Biederman, J Mick, E Wozniak, J Harpold, T Aleardi, M Dougherty, M TI A prospective open-label long-term treatment trial of risperidone monotherapy in children and adolescents with bipolar disorder SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 18th ECNP Congress 2005 CY OCT 22-26, 2005 CL Amsterdam, NETHERLANDS SP ECNP C1 Massachusetts Gen Hosp, Boston, MA 02114 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 S602 EP S603 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 992CA UT WOS:000233860601258 ER PT J AU Biederman, J Monuteaux, M AF Biederman, J Monuteaux, M TI Is cigarette smoking a gateway drug to subsequent alcohol and illicit drug use disorders: a controlled study of youth with and without ADHD SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 18th ECNP Congress 2005 CY OCT 22-26, 2005 CL Amsterdam, NETHERLANDS SP ECNP C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 2 TC 1 Z9 1 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 S589 EP S590 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 992CA UT WOS:000233860601229 ER PT J AU Biederman, J Mick, E Monuteaux, M Faraone, S AF Biederman, J Mick, E Monuteaux, M Faraone, S TI Long term outcome of boys and girls with attention deficit hyperactivity disorder: results of two controlled follow up studies SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 18th ECNP Congress 2005 CY OCT 22-26, 2005 CL Amsterdam, NETHERLANDS SP ECNP C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. SUNY Upstate Med Univ, Ctr Gene Res, Syracuse, NY 13210 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 S352 EP S352 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 992CA UT WOS:000233860600120 ER PT J AU Cohen, L Kornstein, S Entsuah, R Ortega-Leon, W Tummala, R AF Cohen, L Kornstein, S Entsuah, R Ortega-Leon, W Tummala, R TI Comparing age and gender responses during treatment with venlafaxine and selective serotonin reuptake inhibitors SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 18th ECNP Congress 2005 CY OCT 22-26, 2005 CL Amsterdam, NETHERLANDS SP ECNP C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Virginia Commonwealth Univ, Richmond, VA 23284 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 S438 EP S438 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 992CA UT WOS:000233860600318 ER PT J AU Cusin, C Perlis, RH Amsterdam, JD Quitkin, FM Reimherr, FW Zajecka, J Beasley, CM Fava, M AF Cusin, C Perlis, RH Amsterdam, JD Quitkin, FM Reimherr, FW Zajecka, J Beasley, CM Fava, M TI Early symptomatic worsening during treatment with fluoxetine in major depression: prevalence and implications SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 18th ECNP Congress 2005 CY OCT 22-26, 2005 CL Amsterdam, NETHERLANDS SP ECNP C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. Univ Penn, Ctr Med, Univ Sci Ctr, Philadelphia, PA 19104 USA. Columbia Univ, Sch Med, New York, NY USA. New York State Psychiat Inst & Hosp, New York, NY USA. Univ Utah, Sch Med, Salt Lake City, UT 84112 USA. Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. Eli Lilly & Co, Indianapolis, IN 46285 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 S455 EP S455 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 992CA UT WOS:000233860600357 ER PT J AU Henderson, D Copeland, PM Borba, CP Nguyen, DD Evins, AE Zhang, H Hayden, D Freudenreich, O Cather, C Schoenfeld, D Goff, DC AF Henderson, D Copeland, PM Borba, CP Nguyen, DD Evins, AE Zhang, H Hayden, D Freudenreich, O Cather, C Schoenfeld, D Goff, DC TI A comparison of the effects of quetiapine and olanzapine on glucose metabolism in patients with schizophrenia SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 18th ECNP Congress 2005 CY OCT 22-26, 2005 CL Amsterdam, NETHERLANDS SP ECNP C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. NR 1 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 S494 EP S495 PG 2 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 992CA UT WOS:000233860601014 ER PT J AU Pollack, M Van Ameringen, M Snyder, H Brown, C Ondrasik, J Roy-Byrne, P Rickels, K AF Pollack, M Van Ameringen, M Snyder, H Brown, C Ondrasik, J Roy-Byrne, P Rickels, K TI Tiagabine in generalized anxiety disorder: a randomized, double-blind, placebo-controlled study SO EUROPEAN NEUROPSYCHOPHARMACOLOGY LA English DT Meeting Abstract CT 18th ECNP Congress 2005 CY OCT 22-26, 2005 CL Amsterdam, NETHERLANDS SP ECNP C1 Massachusetts Gen Hosp, Ctr Anxiety & Traumat Stress Disorders, Boston, MA 02114 USA. Cephalon Inc, W Chester, PA 19380 USA. McMaster Univ, Med Ctr, Dept Psychiat & Behav Neurosci, Hamilton, ON L8S 4L8, Canada. Univ Washington, Sch Med, Seattle, WA 98195 USA. Univ Penn, Philadelphia, PA 19104 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 S538 EP S538 PG 1 WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 992CA UT WOS:000233860601111 ER PT J AU MacIntyre, N Crapo, RO Viegi, G Johnson, DC van der Grinten, CPM Brusasco, V Burgos, F Casaburi, R Coates, A Enright, P Gustafsson, P Hankinson, J Jensen, R McKay, R Miller, MR Navajas, D Pedersen, OF Pellegrino, R Wanger, J AF MacIntyre, N Crapo, RO Viegi, G Johnson, DC van der Grinten, CPM Brusasco, V Burgos, F Casaburi, R Coates, A Enright, P Gustafsson, P Hankinson, J Jensen, R McKay, R Miller, MR Navajas, D Pedersen, OF Pellegrino, R Wanger, J TI Standardisation of the single-breath determination of carbon monoxide uptake in the lung SO EUROPEAN RESPIRATORY JOURNAL LA English DT Review DE alveolar-capillary permeability; carbon monoxide; carbon monoxide diffusing capacity of the lungs; carbon monoxide transfer factor of the lungs; gas exchange; inspiratory manoeuvres ID PULMONARY DIFFUSING-CAPACITY; AIR-FLOW LIMITATION; GENERAL-POPULATION SAMPLE; TRANSFER-COEFFICIENT KCO; CAPILLARY BLOOD-VOLUME; ALVEOLAR VOLUME; CIGARETTE-SMOKING; NORMAL VALUES; VENTILATION INHOMOGENEITY; IMPAIRMENT DISABILITY C1 Univ Genoa, I-16132 Genoa, Italy. Duke Univ, Med Ctr, Durham, NC USA. LDS Hosp, Salt Lake City, UT USA. CNR, Inst Clin Physiol, I-56100 Pisa, Italy. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Hosp Maastrict, Maastricht, Netherlands. Hosp Clin Barcelona, Barcelona, Spain. Univ Calif Los Angeles, Med Ctr, Torrance, CA 90509 USA. Hosp Sick Children, Toronto, ON M5G 1X8, Canada. Queen Silvias Childrens Hosp, Gothenburg, Sweden. Hankinson Consulting Inc, Valdosta, GA USA. Univ Hosp Birmingham, NHS Trust, Birmingham, W Midlands, England. Lab Biofis I Bioengn, Barcelona, Spain. Univ Aarhus, Aarhus, Denmark. Azienda Osped S Croce & Carle, Cuneo, Italy. Pharmaceut Res Associates Inc, Lenexa, KS USA. RP Brusasco, V (reprint author), Univ Genoa, V Benedetto XV,6, I-16132 Genoa, Italy. EM vito.brusasco@unige.it RI Navajas, Daniel/E-4233-2010; Burgos, Felip/E-5734-2015 OI Navajas, Daniel/0000-0001-7150-9363; Burgos, Felip/0000-0002-4938-4581 NR 112 TC 839 Z9 870 U1 0 U2 26 PU EUROPEAN RESPIRATORY SOC JOURNALS LTD PI SHEFFIELD PA 146 WEST ST, STE 2.4, HUTTONS BLDG, SHEFFIELD S1 4ES, ENGLAND SN 0903-1936 J9 EUR RESPIR J JI Eur. Resp. J. PD OCT PY 2005 VL 26 IS 4 BP 720 EP 735 DI 10.1183/09031936.05.00034905 PG 16 WC Respiratory System SC Respiratory System GA 971XA UT WOS:000232417000024 PM 16204605 ER PT J AU Retzinger, GS Takayama, K AF Retzinger, GS Takayama, K TI Mitogenicity of a spread film of monophosphoryl lipid A SO EXPERIMENTAL AND MOLECULAR PATHOLOGY LA English DT Article DE monophosphoryl lipid A; lipid A; lipopolysaccharide; adsorbed film; surface properties; mitogenicity; innate immunity ID TREHALOSE 6,6'-DIMYCOLATE; STRUCTURAL DETERMINATION; BIOLOGICAL-ACTIVITIES; MOLECULAR-MECHANISMS; ESCHERICHIA-COLI; LIPOPOLYSACCHARIDE; ENDOTOXIN; PURIFICATION; RECOGNITION; MACROPHAGES AB When spread at the air-water interface, monophosphoryl lipid A (MPLA) forms stable insoluble monolayers that collapse at similar to 55 dyn/ cm. At collapse, the exclusion area of each molecule is similar to 119 angstrom(2), consistent with the cross-sectional area of the lipid's 6 acyl chains. The nominal thickness of such films is similar to 22 angstrom, determined, presumably, by the length of the acyl chains. For biological modeling of MPLA films, a system was developed in which monolayers of the lipid are supported by monodisperse hydrophobic beads of microscopic dimensions. Beads coated with MPLA monolayers within which the nominal area of each molecule is approximately equivalent to the "take-off" area of the lipid at the air-water interface, 280 angstrom(2), are mitogenic for spleen cells. Given the natural occurrence of lipid A in the bacterial cell wall as well as the inherent stability of lipid A films, it seems reasonable to assume that at least some of the biological activities attributed to the lipid derive from its presentation/operation at an interface, i.e., on a surface. We propose beads coated with adsorbed films of lipid A will prove useful tools for modeling the activities of the lipid both in vitro and in vivo, and for elucidating the surface dependency and structural requirements of those activities. (c) 2005 Elsevier Inc. All rights reserved. C1 Univ Cincinnati, Dept Pathol & Lab Med, Cincinnati, OH 45267 USA. William S Middleton Mem Vet Adm Med Ctr, Mycobacteriol Res Lab, Madison, WI 53705 USA. RP Retzinger, GS (reprint author), Univ Cincinnati, Dept Pathol & Lab Med, Cincinnati, OH 45267 USA. EM retzings@email.uc.edu FU NCI NIH HHS [R21CA106257] NR 29 TC 1 Z9 1 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4800 J9 EXP MOL PATHOL JI Exp. Mol. Pathol. PD OCT PY 2005 VL 79 IS 2 BP 161 EP 167 DI 10.1016/j.yexmp.2005.06.004 PG 7 WC Pathology SC Pathology GA 968VF UT WOS:000232190300010 PM 16054128 ER PT J AU Foxe, JJ Simpson, GV Ahlfors, SP Saron, CD AF Foxe, JJ Simpson, GV Ahlfors, SP Saron, CD TI Biasing the brain's attentional set: I. Cue driven deployments of intersensory selective attention SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article; Proceedings Paper CT 5th International Multisensory Research Forum CY JUN 02-05, 2004 CL Barcelona, SPAIN ID POSITRON-EMISSION-TOMOGRAPHY; VERBAL WORKING-MEMORY; EVENT-RELATED POTENTIALS; DORSOLATERAL PREFRONTAL CORTEX; HUMAN EXTRASTRIATE CORTEX; OBJECT-RECOGNITION AREAS; HUMAN FRONTAL-CORTEX; HUMAN VISUAL-CORTEX; SHORT-TERM-MEMORY; SUSTAINED ATTENTION AB Brain activity associated with directing attention to one of two possible sensory modalities was examined using high-density mapping of human event-related potentials. The deployment of selective attention was based on visually presented symbolic cue-words instructing subjects on a trial-by-trial basis, which sensory modality to attend. We measured the spatio-temporal pattern of activation in the approximately 1 second period between the cue-instruction and a subsequent compound auditory-visual imperative stimulus. This allowed us to assess the flow of processing across brain regions involved in deploying and sustaining inter-sensory selective attention, prior to the actual selective processing of the compound audio-visual target stimulus. Activity over frontal and parietal areas showed sensory specific increases in activation during the early part of the anticipatory period (similar to 230 ms), probably representing the activation of fronto-parietal attentional deployment systems for top-down control of attention. In the later period preceding the arrival of the "to-be-attended" stimulus, sustained differential activity was seen over fronto-central regions and parieto-occipital regions, suggesting the maintenance of sensory-specific biased attentional states that would allow for subsequent selective processing. Although there was clear sensory biasing in this late sustained period, it was also clear that both sensory systems were being prepared during the cue-target period. These late sensory-specific biasing effects were also accompanied by sustained activations over frontal cortices that also showed both common and sensory specific activation patterns, suggesting that maintenance of the biased state includes top-down inputs from generators in frontal cortices, some of which are sensory-specific regions. These data support extensive interactions between sensory, parietal and frontal regions during processing of cue information, deployment of attention, and maintenance of the focus of attention in anticipation of impending attentionally relevant input. C1 Nathan S Kline Inst Psychiat Res, Program Cognit Neurosci & Schizophrenia, Cognit Neurophysiol Lab, Orangeburg, NY 10962 USA. CUNY City Coll, Dept Psychol, Program Cognit Neurosci, New York, NY 10031 USA. Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. Univ Calif Davis, Ctr Mind & Brain, Davis, CA 95616 USA. RP Foxe, JJ (reprint author), Nathan S Kline Inst Psychiat Res, Program Cognit Neurosci & Schizophrenia, Cognit Neurophysiol Lab, 140 Old Orangeburg Rd, Orangeburg, NY 10962 USA. EM foxe@nki.rfmh.org RI Ahlfors, Seppo/P-3644-2016; OI Foxe, John/0000-0002-4300-3098 FU NIMH NIH HHS [MH11431, MH63434, MH65350, R01 MH065350, R01 MH065350-05, R03 MH063434, R03 MH063434-01A1]; NINDS NIH HHS [NS27900] NR 126 TC 38 Z9 39 U1 5 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD OCT PY 2005 VL 166 IS 3-4 BP 370 EP 392 DI 10.1007/s00221-005-2378-7 PG 23 WC Neurosciences SC Neurosciences & Neurology GA 976GQ UT WOS:000232721400010 PM 16086144 ER PT J AU Yang, J Li, TS AF Yang, J Li, TS TI The ciliary rootlet interacts with kinesin light chains and may provide a scaffold for kinesin-1 vesicular cargos SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE rootletin; APP; presenilin 1; photoreceptor; ciliated cells; vesicular transport and cytoskeleton ID AMYLOID PRECURSOR PROTEIN; AXONAL-TRANSPORT; INTERMEDIATE-FILAMENTS; BINDING; LOCALIZATION; MICROTUBULES; EXPRESSION; SECRETASE; GENES AB The ciliary rootlet is a large striated fibrous network originating from basal bodies in ciliated cells. To explore its postulated role in intracellular transport, we investigated the interaction between kinesin light chains (KLCs) and rootletin, the structural component of ciliary rootlets. We show here that KLCs directly interact with rootletin and are located along ciliary rootlets. Their interactions are mediated by the heptad repeats of KLCs. Further studies found that these interactions tethered kinesin heavy chains along ciliary rootlets. However, the ciliary rootlet-bound kinesin-1 did not recruit microtubules or move along ciliary rootlets. Additionally, amyloid precursor protein (APP; a kinesin-1 vesicular cargo receptor) and presenilin 1 (a presumed cargo of APP/kinesin-1) were found to be enriched along the rootletin fibers, suggesting that the interaction between ciliary rootlets and kinesin-1 recruits APP and presenilin 1 along ciliary rootlets. These findings indicate that ciliary rootlets may provide a scaffold for kinesin-1 vesicular cargos and, thus, play a role in the intracellular transport in ciliated cells. (c) 2005 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Berman Gund Lab Study Retinal Degenerat, Boston, MA 02114 USA. RP Yang, J (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Berman Gund Lab Study Retinal Degenerat, 243 Charles St, Boston, MA 02114 USA. EM jun_yang@meei.harvard.edu FU NEI NIH HHS [EY14426, EY14104] NR 28 TC 23 Z9 25 U1 0 U2 0 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 379 EP 389 DI 10.1016/j.yexcr.2005.05.026 PG 11 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 969TT UT WOS:000232258400014 PM 16018997 ER PT J AU Goody, RJ Hoyt, CC Tyler, KL AF Goody, RJ Hoyt, CC Tyler, KL TI Reovirus infection of the CNS enhances NOS expression in areas of virus-induced injury SO EXPERIMENTAL NEUROLOGY LA English DT Article DE reovirus; nitric oxide; viral encephalitis; nitric oxide synthase; neurons; microglia ID NITRIC-OXIDE SYNTHASE; CENTRAL-NERVOUS-SYSTEM; NF-KAPPA-B; INDUCED APOPTOSIS REQUIRES; IN-VIVO EXPRESSION; TRANSCRIPTION FACTOR; NEURONAL APOPTOSIS; S-NITROSYLATION; DNA-BINDING; INHIBITION AB Nitric oxide (NO) has been implicated as a contributor to the host's innate defense against viral infections including those affecting the CNS. Reovirus infection of the CNS is a classic experimental system for understanding the pathogenesis of neurotropic viral infection. Infection with serotype 3 strains is associated with perturbations in various cellular signaling pathways including NF-kappa B and NO plays a regulatory role in many of these same pathways. We therefore examined whether NO production is dysregulated following reovirus serotype 3 strain Abney (T3A) infection of the mouse CNS. Nitric oxide synthase (NOS) activity was significantly higher in brain homogenates from T3A-infected animals compared to mock infected. Increased NOS activity correlated with inducible NOS (iNOS) expression in brain homogenates of M-infected animals. Expression of iNOS was confined to areas of viral infection and injury. T3A infection of primary neuronal and glial cultures was also associated with enhanced expression of iNOS. Immunocytochemical studies of primary glial cultures demonstrated that, in addition to its known neuronotropism, T3A was also capable of infecting immature microglial cells. T3A infection did not alter expression of either neuronal or endothelial NOS isoforms in neuronal or glial cultures or in mouse brain. The NO donor S-Nitroso-N-acetyl penicillamine (SNAP) significantly inhibited T3A growth in neuronal cultures, conversely the NOS inhibitor N-omega-Nitro-L-arginine methyl ester hydrochloride (L-NAME) augmented viral growth. Our findings provide the first evidence of reovirus-induced iNOS expression and the first demonstration that NO inhibits mammalian reovirus replication, suggesting that NO may play an antiviral role during reovirus infection. (c) 2005 Elsevier Inc. All rights reserved. C1 Univ Colorado, Hlth Sci Ctr, Dept Neurol B182, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Denver, CO 80220 USA. Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Microbiol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Immunol, Denver, CO 80262 USA. RP Tyler, KL (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Neurol B182, 4200 E 9th Ave, Denver, CO 80262 USA. EM Ken.Tyler@uchse.edu FU NINDS NIH HHS [R01 NS050138-04, R01 NS051403-03, R01 NS051403, R01 NS050138] NR 52 TC 18 Z9 18 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 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD OCT PY 2005 VL 195 IS 2 BP 379 EP 390 DI 10.1016/j.expneurol.2005.05.016 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 968VI UT WOS:000232190600011 PM 16004984 ER PT J AU Becker, CM Sampson, DA Rupnick, MA Rohan, RM Efstathiou, JA Short, SM Taylor, GA Folkman, J D'Amato, RJ AF Becker, CM Sampson, DA Rupnick, MA Rohan, RM Efstathiou, JA Short, SM Taylor, GA Folkman, J D'Amato, RJ TI Endostatin inhibits the growth of endometriotic lesions but does not affect fertility SO FERTILITY AND STERILITY LA English DT Article; Proceedings Paper CT 20th Annual Meeting of the European-Society-of-Human-Reproduction-and-Embryology CY JUN 27-30, 2004 CL Berlin, GERMANY SP European Soc Human Reprod & Embryol DE endostatin; angiogenesis inhibitors; reproduction; endometriosis; toxicity ID CORPUS-LUTEUM DEVELOPMENT; PERITONEAL ENDOMETRIOSIS; ANGIOGENESIS INHIBITOR; ANTIANGIOGENIC AGENTS; MURINE MODEL; FACTOR VEGF; ANGIOSTATIN; THALIDOMIDE; INDUCTION; HYPOXIA AB Objective: To determine whether endometriosis can be treated with angiogenesis inhibitor endostatin and the effect of this treatment on fertility and reporduction. Design: Pharmacological intervention in a surgically induced model of endometriosis and female mice undergoing mating. Setting: Animal research facility. Animal(s): Eight-week-old, female C57BL/6 and SCID mice. Intervention(s): After implantation of autologous endometrium, mice received endostatin or the vehicle-matched control for 4 weeks. For the reproductive function study, mice receive endostatin or vehicle were matedand reproductive functions were observed. Main Outcome Measure(s): Growth of endometriotric lesions after 4 weeks of treatment, estrous cycling, corpusluteum formation, serum hormone levels, and mating time as fertility meaures; and pregnancy, fetal vitality, number , and outcome of litter as reproductive measures. Result(s): Endostatin suppressed the growth of endometriotic lesions by 47% compared with controls. Estrous cycling and corpus luteum formation were normal in both groups. Female mice recieving endostatin were as fertile as mice recieving vehicle, had normal pregnancies, and delivered the same number of pups. The offspring were healthy without teratogenic stigmata and reproduced normally themselves. Conclusion(s): Antiangiogenic therapy with endostatin may present a promising novel, nontoxic therapeutic option for patients with endometriosis. C1 Harvard Univ, Sch Med, Childrens Hosp, Vasc Biol Program,Dept Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Obstet & Gynecol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Cardiol, Boston, MA 02115 USA. Charite, Dept Obstet & Gynecol, Berlin, Germany. MIT, Dept Chem Engn, Cambridge, MA 02139 USA. Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. RP D'Amato, RJ (reprint author), Harvard Univ, Sch Med, Childrens Hosp, Vasc Biol Program,Dept Surg, 300 Longwood Ave, Boston, MA 02115 USA. EM robert.damato@childrens.harvard.edu FU NCI NIH HHS [P01-CA45548] NR 66 TC 71 Z9 84 U1 0 U2 5 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 SU 2 BP 1144 EP 1155 DI 10.1016/j.fertnstert.2005.04.040 PG 12 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 974PU UT WOS:000232604700013 PM 16210006 ER PT J AU Seminara, SB AF Seminara, SB TI Metastin and its g protein-coupled receptor, GPR54: Critical pathway modulating GnRH secretion SO FRONTIERS IN NEUROENDOCRINOLOGY LA English DT Review DE GPR54; Kisspeptin-1; puberty; sexual maturation; administration; expression; mouse knockout ID GONADOTROPIN-RELEASING-HORMONE; IDIOPATHIC HYPOGONADOTROPIC HYPOGONADISM; FEMALE RHESUS-MONKEY; KISS-1 MESSENGER-RNA; LUTEINIZING-HORMONE; KALLMANN-SYNDROME; NEUROPEPTIDE-Y; HYPOTHALAMIC AMENORRHEA; LEPTIN RECEPTOR; PUBERTY AB Photoperiod, food availability, temperature, stress, and hormonal cues are some of the varied signals used by mammalian species to activate or suppress their timing of sexual maturation. All ultimately converge upon gonadotropin-releasing hormone (GnRH) secretion from the hypothalamus. Through its stimulation of LH and FSH from the pituitary, GnRH represents a critical step in the reproductive cascade. While few dispute this central role of GnRH, little is understood of the mechanisms influencing the developmental fate and physiologic controls of GnRH neurons. Identification of the signals which modulate Pulsatile GnRH secretion is critical to advancing understanding of normal puberty and reproductive competency. The recent identification of loss-of-function mutations in GPR54, a receptor for kisspeptin-1. has highlighted a new pathway for the timing of puberty and reproductive control. (c) 2005 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. RP Seminara, SB (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, Bartlett Hall Extens 5,Fruit St, Boston, MA 02114 USA. EM sseminara@partners.org FU NICHD NIH HHS [U54 HD028138, R01 HD043341] NR 73 TC 55 Z9 58 U1 0 U2 11 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-3022 J9 FRONT NEUROENDOCRIN JI Front. Neuroendocrinol. PD OCT-DEC PY 2005 VL 26 IS 3-4 BP 131 EP 138 DI 10.1016/j.yfrne.2005.10.001 PG 8 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 998AU UT WOS:000234291100003 PM 16309735 ER PT J AU Ko, CW Sonnenberg, A AF Ko, CW Sonnenberg, A TI Comparing risks and benefits of colorectal cancer screening in elderly patients SO GASTROENTEROLOGY LA English DT Article ID FECAL-OCCULT-BLOOD; RANDOMIZED CONTROLLED TRIAL; COST-EFFECTIVENESS; FLEXIBLE SIGMOIDOSCOPY; ONE-TIME; COLONOSCOPY; MORTALITY; COMPLICATIONS; PERFORATION; POPULATION AB Background& Aims: In patients with limited life expectancy, the risks of colorectal cancer screening may outweigh the benefits. The aim of this study was to quantify risks and benefits of different screening strategies in elderly patients with varying life expectancies. Methods: We examined risks and benefits of screening in patients aged 70-94 years with differing health status using 3 strategies: annual fecal occult blood tests, flexible sigmoldoscopy every 5 years, or colonoscopy every :10 years. We compared the number needed to screen to prevent one cancer-related death and the number needed to encounter one screening-related complication for different strategies. Results: The potential benefit from screening varied widely with age, life expectancy, and screening modality. One cancer-related death would be prevented by screening 42 healthy men aged 70-74 years with colonoscopy, 178 healthy women aged 70-74 years with fecal occult blood tests, 431 women aged 75-79 years in poor health with colonoscopy, or 945 men aged 80-84 years in average health with fecal occult blood tests. Colonoscopy screening had the greatest benefit but the highest risk of complications. The potential for screening-related complications was greater than estimated benefit in some population subgroups aged 70 years and older. At all ages and life expectancies, the potential reduction in mortality from screening outweighed the risk of colon oscopy-related death. Conclusions: The potential benefits and risks of screening vary in elderly patients of different life expectancies. For any individual patient, the potential for harm from screening must be weighed against the likelihood of benefit, especially with shorter life expectancy. C1 Univ Washington, Div Gastroenterol, Dept Med, Seattle, WA 98195 USA. Oregon Hlth Sci Univ, Dept Med, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Portland VA Med Ctr, Portland, OR 97201 USA. RP Ko, CW (reprint author), Univ Washington, Div Gastroenterol, Dept Med, Box 356424, Seattle, WA 98195 USA. EM cwko@u.washington.edu NR 34 TC 49 Z9 50 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD OCT PY 2005 VL 129 IS 4 BP 1163 EP 1170 DI 10.1053/j.gastro.2005.07.027 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 974IX UT WOS:000232586000006 PM 16230070 ER PT J AU Abraham, NS El-Serag, HB Johnson, ML Hartman, C Richardson, P Ray, WA Smalley, W AF Abraham, NS El-Serag, HB Johnson, ML Hartman, C Richardson, P Ray, WA Smalley, W TI National adherence to evidence-based guidelines for the prescription of nonsteroidal anti-inflammatory drugs SO GASTROENTEROLOGY LA English DT Article; Proceedings Paper CT 69th Annual Meeting of the American-College-of-Gastroenterology CY OCT 29-NOV 03, 2004 CL Orlando, FL SP Amer Coll Gastroenterol ID SERIOUS GASTROINTESTINAL COMPLICATIONS; PEPTIC-ULCER; RHEUMATOID-ARTHRITIS; CONTROLLED-TRIAL; ELDERLY PERSONS; CONSENSUS PANEL; RISK; OSTEOARTHRITIS; OMEPRAZOLE; PREVENTION AB Background & Aims: Our objective was to assess adherence to evidence-based guidelines by providers of the Department of Veterans Affairs nationwide. Methods: This was a cross-sectional study among veterans prescribed a nonsteroidal anti-inflammatory drug (NSAID) from January 1, 2002, to December 31, 2002. Prescription data were linked to inpatient and outpatient medical records and death files. The population was characterized as high risk based on the following: age 65 years or older, concurrent corticosterold or anticoagulant use, history of peptic ulcer, and high average daily dose of NSAIDs. Adherence was defined as the prescription of a traditional NSAID with gastroprotection or a coxib in high-risk NSAID users. Univariate and multivarlate analyses assessed the potential predictors of adherence. Results: Three hundred three thousand seven hundred eighty-seven met our definition of high risk. Most (97.3%) were male; 55.6% were white, 9.6% black, and 34.8% of other/unknown race. Age 65 years or older was the largest high-risk subset (87.1%). Overall, only 27.2% of high-risk veterans (n = 82,766) were prescribed an adherent strategy. Among veterans with at least 2 risk factors, adherence was 39.7%; among those with 3 risk factors, adherence was 41.8%. Predictors of adherence included history of upper gastrointestinal events, anticoagulant use, rheumatologic disease, high Deyo comorbidity index score, use of low-dose salicylates, and concurrent corticosterold use. Predictors of nonadherence included prescriptions >= 90 days and high average daily dose of NSAIDs. Conclusions: Adherence to evidence-based guidelines for safe prescription of NSAIDs in the Department of Veterans Affairs is low (27.2%). The likelihood of adherence is further decreased if veterans are prescribed NSAIDs for 2:90 days. C1 Michael E DeBakey Vet Affairs Med Ctr, Dept Gastroenterol, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. Houston Ctr Qual Care & Utilizat Studies, Houston, TX 77030 USA. Vanderbilt Univ, Dept Prevent Med, Nashville, TN USA. Vanderbilt Univ, Dept Med, Nashville, TN USA. Vet Affairs Tennessee Valley Healthcare Syst, Geriatr Res Educ & Clin Ctr, Nashville, TN USA. RP Abraham, NS (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Dept Gastroenterol, 2002 Holcombe Blvd 152, Houston, TX 77030 USA. EM nabraham@bcm.tmc.edu NR 43 TC 94 Z9 96 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD OCT PY 2005 VL 129 IS 4 BP 1171 EP 1178 DI 10.1053/j.gastro.2005.08.003 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 974IX UT WOS:000232586000007 PM 16230071 ER PT J AU Hsiung, PL Pantanowitz, L Aguirre, AD Chen, Y Phatak, D Ko, TH Bourquin, S Schnitt, SJ Raza, S Connolly, JL Mashimo, H Fujimoto, JG AF Hsiung, PL Pantanowitz, L Aguirre, AD Chen, Y Phatak, D Ko, TH Bourquin, S Schnitt, SJ Raza, S Connolly, JL Mashimo, H Fujimoto, JG TI Ultrahigh-resolution and 3-dimensional optical coherence tomography ex vivo imaging of the large and small intestines SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID MAGNIFICATION CHROMOSCOPIC COLONOSCOPY; HUMAN GASTROINTESTINAL-TRACT; IN-VIVO; HIGH-SPEED; CONTINUUM GENERATION; BARRETTS-ESOPHAGUS; GI TRACT; MU-M; BIOPSY; FIBER AB Background: Ultrahigh-resolution optical coherence tomography (OCT) has an axial resolution of < 5 mu m, 2 to 3 times finer than standard OCT This study investigates ultrahigh-resolution and three-dimensional OCT for ex vivo imaging of the large and small intestines and correlates images with histology. Methods: Ultrahigh-resolution OCT imaging was performed on fresh surgical specimens from the large and small intestines in the pathology laboratory, and images were correlated with histology. OCT was performed at 1.3-mu m wavelength with 4.5-mu m axial x 11-mu m transverse resolution and at 1.1-mu m wavelength with 3.5-mu m axial x 6-mu m transverse resolution. Three-dimensional OCT also was investigated. Results: Normal and pathologic areas from 23 surgical specimens of the large and small intestines were imaged. Ultrahigh-resolution OCT distinguished the epithelia] layer of the mucosa and visualized individual villi, glands, and crypts. Finer transverse resolutions improved visualization of features, e.g., the epithelium, but reduced the depth of field. Architectural distortion of glands from inflammatory and neoplastic processes was observed. Three-dimensional rendering enabled visualization of surface pit pattern and mucosal folds as well as subsurface crypt microstructure. Conclusions: This study evaluates new OCT technology and can provide a baseline for interpreting future ultrahigh-resolution endoscopic OCT studies. C1 MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. MIT, Elect Res Lab, Cambridge, MA 02139 USA. Baystate Med Ctr, Dept Pathol, Springfield, MA 01199 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02115 USA. VA Boston Healthcare Syst, Boston, MA USA. RP Fujimoto, JG (reprint author), MIT, Dept Elect Engn & Comp Sci, 50 Vassar St,Rm 36-361, Cambridge, MA 02139 USA. FU NCI NIH HHS [R01-CA75289-06] NR 59 TC 37 Z9 38 U1 0 U2 4 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD OCT PY 2005 VL 62 IS 4 BP 561 EP 574 DI 10.1016/j.gie.2005.05.006 PG 14 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 970ZM UT WOS:000232350900017 PM 16185971 ER PT J AU Zhang, J Attar, E Cohen, K Crumpacker, C Scadden, D AF Zhang, J Attar, E Cohen, K Crumpacker, C Scadden, D TI Silencing p21(Waf1/Cip1/Sdi1) expression increases gene transduction efficiency in primitive human hematopoietic cells SO GENE THERAPY LA English DT Article DE p21; RNAi; transduction efficiency; hematopoietic stem cells ID STEM-CELLS; QUANTITATIVE ASSAY; LENTIVIRAL VECTORS; MAMMALIAN-CELLS; CD34(+) CELLS; BONE-MARROW; VIRUS; INFECTION; RECEPTOR; ENTRY AB Adult hematopoietic and other tissue stem cells have highly constrained cell cycling that limits their susceptibility to standard gene therapy vectors, which depend upon chromosomal integration. Using cytokine cocktails to increase transduction efficiency often compromises subsequent stem cell function in vivo. We previously showed that p21(Waf1/Cip1/Sdi1) (p21) mediates stem cell quiescence in vivo and decreasing its expression ex vivo leads to an expansion of stem cell pool in vivo. Here, we report that application of p21 specific siRNA increased the gene transduction efficiency in hematopoietic stem cells while preserving cell multipotentiality. Both types of siRNA, synthesized siRNA and transcribed shRNA, reduced p21 expression in target cells by 85 - 98%. The effect of RNAi in these cells was transient and the level of p21 mRNA returned to base line 14 - 28 days after siRNA treatment. This brief interval of reduction, however, was sufficient to increase transduction efficiency to two- to four-fold in cell cultures, and followed by a seven-to eight-fold increase in mice. The RNAi treated, lentivector-transduced CD34(+) cells retained multipotentiality as assessed in vitro by colony formation assay and in vivo by NOD/SCID mouse transplantation assay. Reduction of p21 resulted in an increased chromosomal integration of lentivector into target cellular DNA. Taken together, both synthesized and transcribed siRNA knocked down p21 expression in human CD34+ hematopoietic stem/progenitor cells. Silencing p21 expression increased gene transduction efficiency and vector integration while retaining stem cell multipotentiality. Thus, RNAi targeting of p21 is a useful strategy to increase stem cell gene transfer efficiency. Decreasing p21 expression transiently while increasing gene-transfer vector integration may ultimately facilitate clinical applications of gene therapy. C1 Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA 02215 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Regenerat Med & Technol, Boston, MA USA. RP Zhang, J (reprint author), Beth Israel Deaconess Med Ctr, Div Infect Dis, Dana 617,330 Brookline Ave, Boston, MA 02215 USA. FU NHLBI NIH HHS [HL044851-13]; NIAID NIH HHS [AI055313] NR 32 TC 26 Z9 27 U1 0 U2 2 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 19 BP 1444 EP 1452 DI 10.1038/sj.gt.3302544 PG 9 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 965VM UT WOS:000231978500005 PM 15877047 ER PT J AU McClatchey, AI Giovannini, M AF McClatchey, AI Giovannini, M TI Membrane organization and tumorigenesis - the NF2 tumor suppressor, Merlin SO GENES & DEVELOPMENT LA English DT Review DE ERM proteins; Merlin/NF2; Schwann cells; ependyma; membrane organization; meninges ID NEUROFIBROMATOSIS TYPE-2 GENE; NERVE SHEATH TUMORS; SCHWANN-CELL PROLIFERATION; CHOROID-PLEXUS EPITHELIUM; HUMAN ARACHNOID VILLI; ERM PROTEIN EZRIN; FERM DOMAIN; E-CADHERIN; VESTIBULAR-SCHWANNOMA; SPORADIC MENINGIOMAS AB The NF2 tumor-suppressor gene was cloned more than a decade ago, but the function of its encoded protein, Merlin, remains elusive. Merlin, like the closely related ERM proteins, appears to provide regulated linkage between membrane-associated proteins and the actin cytoskeleton and is therefore poised to function in receiving and interpreting signals from the extracellular milieu. Recent studies suggest that Merlin may coordinate the processes of growth-factor receptor signaling and cell adhesion. Varying use of this organizing activity by different types of cells could provide an explanation for the unique spectrum of tumors associated with NF2 deficiency in mammals. C1 Massachusetts Gen Hosp, Dept Pathol, Ctr Canc Res, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. CEPH, INSERM, U674, Fdn Jean Dausset, Paris, France. Inst Univ Hematol, Paris, France. RP McClatchey, AI (reprint author), Massachusetts Gen Hosp, Dept Pathol, Ctr Canc Res, Charlestown, MA 02129 USA. EM mcclatch@helix.mgh.harvard.edu NR 116 TC 151 Z9 156 U1 0 U2 11 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 1 PY 2005 VL 19 IS 19 BP 2265 EP 2277 DI 10.1101/gad.1335605 PG 13 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 972DA UT WOS:000232433000003 PM 16204178 ER PT J AU Inoue, H Hisamoto, N An, JH Oliveira, RP Nishida, E Blackwell, TK Matsumoto, K AF Inoue, H Hisamoto, N An, JH Oliveira, RP Nishida, E Blackwell, TK Matsumoto, K TI The C. elegans p38 MAPK rathway regulates nuclear ocalization of the transcription factor SKN-1 in oxidative stress response SO GENES & DEVELOPMENT LA English DT Article DE C. elegans; oxidative stress; p38 MAP kinase; SKN-1 ID CAENORHABDITIS-ELEGANS; INNATE IMMUNITY; PROTEIN; PATHWAY; DOMAIN; GENE; EXPRESSION; SEQUENCES; JNK AB The evolutionarily conserved p38 mitogen-activated protein kinase (MAPK) cascade is an integral part of the response to a variety of environmental stresses. Here we show that the Caenorhabditis elegans PMK-1 p38 MAPK pathway regulates the oxidative stress response via the CNC transcription factor SKN-1. In response to oxidative stress, PMK-1 phosphorylates SKN-1, leading to its accumulation in intestine nuclei, where SKN-1 activates transcription of gcs-1, a phase II detoxification enzyme gene. These results delineate the C. elegans p38 MAPK signaling pathway leading to the nucleus that responds to oxidative stress. C1 Nagoya Univ, Dept Mol Biol, Grad Sch Sci, Inst Adv Res,Chikusa Ku, Nagoya, Aichi 4648602, Japan. CREST, Japan Sci & Technol Corp, Chikusa Ku, Nagoya, Aichi 4648602, Japan. Harvard Univ, Sch Med, Sect Dev & Stem Cell Biol, Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02215 USA. Kyoto Univ, Dept Cell & Dev Biol, Grad Sch Biostudies, Sakyo Ku, Kyoto 6068502, Japan. RP Matsumoto, K (reprint author), Nagoya Univ, Dept Mol Biol, Grad Sch Sci, Inst Adv Res,Chikusa Ku, Nagoya, Aichi 4648602, Japan. EM g44177a@nucc.cc.nagoya-u.ac.jp RI Oliveira, Riva/J-8408-2013 OI Oliveira, Riva/0000-0002-4917-7646 FU NIGMS NIH HHS [GM62891, R01 GM062891] NR 22 TC 158 Z9 173 U1 0 U2 17 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 1 PY 2005 VL 19 IS 19 BP 2278 EP 2283 DI 10.1101/gad.1324805 PG 6 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 972DA UT WOS:000232433000004 PM 16166371 ER PT J AU Burns, CE Traver, D Mayhall, E Shepard, JL Zon, LI AF Burns, CE Traver, D Mayhall, E Shepard, JL Zon, LI TI Hematopoietic stem cell fate is established by the Notch-Runx pathway SO GENES & DEVELOPMENT LA English DT Article DE stem cell; Notch; Runx; AGM; zebrafish; irradiation ID BONE-MARROW NICHE; UBIQUITIN LIGASE; GENE-EXPRESSION; IN-VIVO; DEFINITIVE HEMATOPOIESIS; ADULT HEMATOPOIESIS; PROGENITOR CELLS; SONIC-HEDGEHOG; SELF-RENEWAL; DANIO-RERIO AB identifying the molecular pathways regulating hematopoictic stem cell (HSC) specification, self-renewal, and expansion remains a fundamental goal of both basic and clinical biology. Here, we analyzed the effects of Notch signaling on HSC number during zebrafish development and adulthood, defining a critical pathway for stem cell specification. The Notch signaling mutant mind bomb displays normal embryonic hematopoiesis but fails to specify adult HSCs. Surprisingly, transient Notch activation during embryogenesis via an inducible transgenic system led to a Runx1-dependent expansion of HSCs in the aorta-gonad-mesonephros (AGM) region. In irradiated adults, Notch activity induced runx1 gene expression and increased multilineage hematopoietic precursor cells approximately threefold in the marrow. This increase was followed by the accelerated recovery of all the mature blood cell lineages. These data define the Notch-Runx pathway as critical for the developmental specification of HSC fate and the subsequent homeostasis of HSC number, thus providing a mechanism for amplifying stem cells in vivo. C1 Harvard Univ, Sch Med, Stem Cell Program, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Hematol Oncol, Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Howard Hughes Med Inst,Harvard Stem Cell Inst, Boston, MA 02115 USA. Univ Calif San Diego, Sect Cell & Dev Biol, La Jolla, CA 92093 USA. RP Zon, LI (reprint author), Harvard Univ, Sch Med, Stem Cell Program, Boston, MA 02115 USA. EM zon@enders.tch.harvard.edu FU NHLBI NIH HHS [R01 HL048801, 5 R01 HL48801-13]; NIDDK NIH HHS [1 K01 DK067179-01 A1, K01 DK067179] NR 72 TC 237 Z9 250 U1 4 U2 15 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 1 PY 2005 VL 19 IS 19 BP 2331 EP 2342 DI 10.1101/gad.1337005 PG 12 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 972DA UT WOS:000232433000011 PM 16166372 ER PT J AU Al Jurdi, R Pulakhandam, S Kunik, ME Marangell, LB AF Al Jurdi, R Pulakhandam, S Kunik, ME Marangell, LB TI Late-life mania - Assessment and treatment of late-life manic symptoms SO GERIATRICS LA English DT Article ID BIPOLAR DISORDER; EFFICACY; LITHIUM; ONSET; AGE C1 Michael E DeBakey Vet Affairs Med Ctr, Mood Disorders Clin, Houston, TX USA. Baylor Coll Med, Menninger Dept Psychiat, Houston, TX 77030 USA. Houston Ctr Qual Care & Utilizat Studies, Houston, TX USA. Baylor Coll Med, Menninger Dept Psychiat & Behav Sci, Houston, TX 77030 USA. RP Al Jurdi, R (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Mood Disorders Clin, Houston, TX USA. NR 14 TC 2 Z9 2 U1 0 U2 0 PU ADVANSTAR COMMUNICATIONS PI DULUTH PA 131 W FIRST ST, DULUTH, MN 55802 USA SN 0016-867X J9 GERIATRICS JI Geriatrics PD OCT PY 2005 VL 60 IS 10 BP 18 EP + PG 5 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 978ZD UT WOS:000232910800009 PM 16218763 ER PT J AU Huynh, T Sanchez-Reilly, S AF Huynh, T Sanchez-Reilly, S TI Geriatric assessment clinic in a major cancer center: A needed interdisciplinary partnership among geriatrics and oncology SO GERONTOLOGIST LA English DT Meeting Abstract C1 Univ Texas, Hlth Sci Ctr, S Texas Vet Hlth Care Syst, GRECC, San Antonio, TX 78285 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 10 EP 11 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 988QF UT WOS:000233615000021 ER PT J AU Underwood, W Copeland, L Elshaikh, M Penner, L Jackson, J AF Underwood, W Copeland, L Elshaikh, M Penner, L Jackson, J TI The use of brachytherapy for the treatment of clinically localized prostate cancer in older aged men SO GERONTOLOGIST LA English DT Meeting Abstract C1 Univ Michigan, Ann Arbor, MI 48109 USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. Karmanos Canc Inst, Detroit, MI 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 10 EP 10 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 988QF UT WOS:000233615000019 ER PT J AU Awerbach, J Spiro, A Vokonas, P AF Awerbach, J Spiro, A Vokonas, P TI Short-term heart rate variability and aging in the presence of circulatory diseases: The VA Normative Aging Study SO GERONTOLOGIST LA English DT Meeting Abstract C1 VA Boston Healthcare Syst, Boston, MA 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 13 EP 13 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 988QF UT WOS:000233615000030 ER PT J AU Cherlin, E Schulman-Green, D Prigerson, H Kasl, S Johnson-Hurzeler, R Bradley, E Barry, C AF Cherlin, E Schulman-Green, D Prigerson, H Kasl, S Johnson-Hurzeler, R Bradley, E Barry, C TI Services for family caregivers: Who uses, why and why not? SO GERONTOLOGIST LA English DT Meeting Abstract C1 Yale Univ, Sch Epidemiol & Publ Hlth, New Haven, CT USA. Yale Univ, Sch Nursing, New Haven, CT USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Connecticut Hospice, Branford, CT USA. John D Thomson Hospice, Inst Training Educ & Res, Branford, CT 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 36 EP 37 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 988QF UT WOS:000233615000091 ER PT J AU Chen, Z Sage, C Huang, M Vollrath, M Corey, D Vetter, D AF Chen, Z Sage, C Huang, M Vollrath, M Corey, D Vetter, D TI Generation of functional hair cells in postnatal retinoblastoma knockout mice SO GERONTOLOGIST LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Howard Hughes Med Inst, Boston, MA 02115 USA. Tufts Univ, New England Med Ctr, Boston, MA 02111 USA. NR 0 TC 1 Z9 1 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 53 EP 54 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 988QF UT WOS:000233615000142 ER PT J AU Sonntag, W Carter, C Ikeno, Y Lee, S AF Sonntag, W Carter, C Ikeno, Y Lee, S TI Increased growth hormone and IGF-1 during adolescence are required for longer lifespan in a model of adult-onset growth hormone/IGF-1 deficiency SO GERONTOLOGIST LA English DT Meeting Abstract C1 Wake Forest Univ Hlth Sci, Winston Salem, NC USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Dept Vet Affairs Med Ctr, San Antonio, TX 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 67 EP 68 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 988QF UT WOS:000233615000188 ER PT J AU Abdel-Karim, I Sanchez-Reilly, S AF Abdel-Karim, I Sanchez-Reilly, S TI A combined consultation service in geriatrics and palliative care for geriatric oncology patients: A clinical case SO GERONTOLOGIST LA English DT Meeting Abstract C1 Univ Texas, Hlth Sci Ctr, S Texas Vet Affairs Hlth Care Syst, San Antonio, TX 78285 USA. Univ Texas, Hlth Sci Ctr, GRECC, San Antonio, TX 78285 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 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 112 EP 113 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 988QF UT WOS:000233615000303 ER PT J AU Markland, A Gerety, M Kraus, S Espino, D AF Markland, A Gerety, M Kraus, S Espino, D TI Diabetes and urinary incontinence associations among older, hispanic women SO GERONTOLOGIST LA English DT Meeting Abstract C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX 78285 USA. S Texas Vet Hlth Care Adm, San Antonio, TX 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 121 EP 122 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 988QF UT WOS:000233615000323 ER PT J AU Underwood, W Copeland, L Elshaikh, M Penner, L Jackson, J AF Underwood, W Copeland, L Elshaikh, M Penner, L Jackson, J TI Racial variations in the use of specific prostate cancer treatment modalities SO GERONTOLOGIST LA English DT Meeting Abstract C1 Univ Michigan, Ann Arbor, MI 48109 USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. Karmanos Canc Inst, Detroit, MI 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 125 EP 126 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 988QF UT WOS:000233615000334 ER PT J AU Huynh, T Sanchez-Reilly, S AF Huynh, T Sanchez-Reilly, S TI To treat or not to treat is not the question SO GERONTOLOGIST LA English DT Meeting Abstract C1 Univ Texas, Hlth Sci Ctr, S Texas Vet Hlth Care Syst, GRECC, San Antonio, TX 78285 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 234 EP 235 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 988QF UT WOS:000233615000607 ER PT J AU Owings, K Sanchez-Reilly, S AF Owings, K Sanchez-Reilly, S TI Answering a geriatrics consult in "postoperative dementia": An elderly surgical patient with delirium SO GERONTOLOGIST LA English DT Meeting Abstract C1 Univ Texas, Hlth Sci Ctr, S Texas Vet Hlth Care Syst, GRECC, San Antonio, TX 78285 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 234 EP 234 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 988QF UT WOS:000233615000605 ER PT J AU Hedrick, S Chapko, M Sullivan, J Barry, S Zhou, A Wang, L Guihan, M Manheim, L AF Hedrick, S Chapko, M Sullivan, J Barry, S Zhou, A Wang, L Guihan, M Manheim, L TI Outcomes of the assisted living pilot project: How does assisted living work in VA? SO GERONTOLOGIST LA English DT Meeting Abstract C1 VA Puget Sound Hlth Care Syst, Seattle, WA USA. US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 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 271 EP 272 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 988QF UT WOS:000233615000712 ER PT J AU Guihan, M Thomas, M Hedrick, S AF Guihan, M Thomas, M Hedrick, S TI Participation of assisted living providers in VA Assisted Living Pilot Program SO GERONTOLOGIST LA English DT Meeting Abstract C1 US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Hines, IL 60141 USA. VA Puget Sound Hlth Care Syst, Seattle, WA 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 272 EP 272 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 988QF UT WOS:000233615000713 ER PT J AU Akhtar, A Sanchez-Reilly, S AF Akhtar, A Sanchez-Reilly, S TI Combining geriatrics and palliative care into an inpatient consultation service: A innovative model of care for the elderly SO GERONTOLOGIST LA English DT Meeting Abstract C1 Univ Texas, Hlth Sci Ctr, S Texas Vet Hlth Care Syst, GRECC, San Antonio, TX 78229 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 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 292 EP 293 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 988QF UT WOS:000233615000763 ER PT J AU Roberge, B Chuang, S Cury, A Cumming, K AF Roberge, B Chuang, S Cury, A Cumming, K TI The prevalence of fatigue and the relationship between fatigue, depression and sleep in older adults with heart failure SO GERONTOLOGIST LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 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 330 EP 331 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 988QF UT WOS:000233615000863 ER PT J AU Walker, W Drexler, M Moody-Ayers, S Walker, W AF Walker, W Drexler, M Moody-Ayers, S Walker, W TI Interdisciplinary group behavorial intervention for dementia in long-term care SO GERONTOLOGIST LA English DT Meeting Abstract C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. San Francisco VA Med Ctr, San Francisco, CA 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 337 EP 337 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 988QF UT WOS:000233615000883 ER PT J AU Fonda, S Fultz, N Jenkins, K AF Fonda, S Fultz, N Jenkins, K TI The relationship of body mass to disparate trajectories of total wealth among retirement-aged men and women SO GERONTOLOGIST LA English DT Meeting Abstract C1 Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. Univ Michigan, Ann Arbor, MI 48109 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 391 EP 392 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 988QF UT WOS:000233615001122 ER PT J AU Petersen, N Ford, M Matthiesen, E Cox, V Teng, E Kallen, M AF Petersen, N Ford, M Matthiesen, E Cox, V Teng, E Kallen, M TI Effects of social support on comprehension and recall of consent form information SO GERONTOLOGIST LA English DT Meeting Abstract C1 Baylor Coll Med, VA HRS&D COE, Houston Ctr Qual Care & Utilizat Studies, Houston, TX 77030 USA. Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 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 417 EP 418 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 988QF UT WOS:000233615001208 ER PT J AU Williams, C Williams, B Burgio, K Shuster, J AF Williams, C Williams, B Burgio, K Shuster, J TI Recruiting older adults for medical research: The who, what and why SO GERONTOLOGIST LA English DT Meeting Abstract C1 Univ Alabama, Div Gerontol & Geriatr Med, Birmingham, AL USA. Tuscaloosa VA Med Ctr, Tuscaloosa, AL USA. Birmingham VA Med Ctr, Birmingham, AL 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 468 EP 468 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 988QF UT WOS:000233615001348 ER PT J AU Schnelle, JF Osterweil, D Simmons, SF AF Schnelle, JF Osterweil, D Simmons, SF TI Improving the quality of nursing home care and medical-record accuracy with direct observational technologies SO GERONTOLOGIST LA English DT Article DE observations; nursing home quality assessment; nursing home survey ID MINIMUM DATA SET; RESIDENTS; RELIABILITY AB Nursing home medical-record documentation of dlaily-care occurrence may be inaccurate, and information is not documented about important quality-of-life domains. The inadequacy of medical record data creates a barrier to improving care quality, because it supports an illusion of care consistent with regulations, which reduces the motivation and ability of providers to identify areas for improvement. Observational protocols designed for use by survey and quality-assurance staff can provide the independent information necessary for improving both medical record accuracy and residents' quality of life. Unfortunately, observational protocols currently used in survey and quality-assurance activities are not designed in a manner that is consistent with the scientific principles that guide observational measurement. The purpose of this article is to describe the steps to develop a standardized and scientifically defensible observational system to assess nursing home care quality. C1 Univ Calif Los Angeles, Dept Med, Div Geriatr, Reseda, CA 91335 USA. VA Greater Los Angeles Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Los Angeles, CA USA. Los Angeles Jewish Home Aging, Borun Ctr Gerontol Res, Los Angeles, CA USA. RP Schnelle, JF (reprint author), Univ Calif Los Angeles, Dept Med, Div Geriatr, 7150 Tampa Ave, Reseda, CA 91335 USA. EM jschnell@ucla.edu NR 21 TC 22 Z9 22 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 IS 5 BP 576 EP 582 PG 7 WC Gerontology SC Geriatrics & Gerontology GA 969RH UT WOS:000232251900001 PM 16199391 ER PT J AU Williams, R Brady, C Spiro, A Goral, M Clark-Cotton, M AF Williams, R Brady, C Spiro, A Goral, M Clark-Cotton, M TI Interactive effects of hypertension and diabetes on semantic and letter fluency: Findings from the VA Normative Aging Study SO GERONTOLOGIST LA English DT Meeting Abstract C1 Boston Univ, Sch Med, Boston, MA 02215 USA. VA Boston Healthcare Syst, Boston, MA 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 612 EP 612 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 988QF UT WOS:000233615001717 ER PT J AU Davison, E Rowe, E Pineles, S Gradus, J AF Davison, E Rowe, E Pineles, S Gradus, J TI The relationships among age, psychiatric symptoms, and somatic symptoms in a sample of women veteran mental health patients SO GERONTOLOGIST LA English DT Meeting Abstract C1 VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. Boston Univ, Sch Med, Boston, MA 02215 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 660 EP 661 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 988QF UT WOS:000233615001840 ER PT J AU Tillisch, K Mayer, EA Labus, JS Stains, J Chang, L Naliboff, BD AF Tillisch, K Mayer, EA Labus, JS Stains, J Chang, L Naliboff, BD TI Sex specific alterations in autonomic function among patients with irritable bowel syndrome SO GUT LA English DT Article ID HEART-RATE-VARIABILITY; NERVOUS-SYSTEM FUNCTION; DIARRHEA-PREDOMINANT; VISCERAL PERCEPTION; DEPRESSION SCALE; HOSPITAL ANXIETY; POWER SPECTRUM; IBS PATIENTS; RESPONSES; GENDER AB Background: Irritable bowel syndrome (IBS) is associated with increased psychological symptoms, early life stressors, and alterations in visceral perception and brain responses to noxious visceral stimuli. The autonomic nervous system (ANS) is a likely mediator for these brain-gut interactions. The few studies directly examining ANS measures have been suggestive of alterations in some IBS patients, but no studies to date have examined the potentially critical variables of sex differences or response to visceral stimulation. Aims: ( 1) To test differences in ANS function during rest and during a visceral stressor ( rectosigmoid balloon distension) between IBS patients and healthy control subjects. ( 2) To examine the role of sex on the autonomic responses of IBS patients. Methods: Baseline autonomic measures were evaluated from 130 Rome I positive IBS patients and 55 healthy control subjects. Data were also collected from a subset of 46 IBS patients and 16 healthy control subjects during a sigmoid balloon distension study. Heart rate variability measures of peak power ratio (PPR) and peak power high frequency (PPHF) were analysed to assess sympathetic balance and parasympathetic response, respectively. Peripheral sympathetic response was measured by skin conductance. Results: IBS patients showed a greater skin conductance response to visceral distension than controls. IBS patients had higher PPR and lower PPHF across conditions. Male IBS patients had higher skin conductance and PPR than females and lower PPHF. Conclusions: IBS patients have altered autonomic responsiveness to a visceral stressor, with increased sympathetic and decreased parasympathetic activity. These differences are predominantly seen in males. C1 Univ Calif Los Angeles, David Geffen Sch Med, CNS WH Ctr Neurovisceral Sci & Womens Hlth, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90073 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Tillisch, K (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, CNS WH Ctr Neurovisceral Sci & Womens Hlth, CURE Bldg 115,Room 223,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM ktillisch@mednet.ucla.edu FU NIDDK NIH HHS [P50 DK064539]; NINR NIH HHS [NR007768, R01 NR007768] NR 46 TC 85 Z9 88 U1 2 U2 3 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 1396 EP 1401 DI 10.1136/gut.2004.058685 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 964JC UT WOS:000231876000014 PM 15923667 ER PT J AU Anand, BS Thornby, J AF Anand, BS Thornby, J TI Alcohol has no effect on hepatitis C virus replication: a meta-analysis SO GUT LA English DT Article ID LIVER-DISEASE; NATURAL-HISTORY; HEPATOCELLULAR-CARCINOMA; INFECTION; PROGRESSION; PREVALENCE; FIBROSIS; CONSUMPTION; CIRRHOSIS; ABUSE AB Background: Patients with chronic hepatitis C virus (HCV) infection who consume large quantities of alcohol have more severe liver disease compared with HCV patients without a history of alcohol consumption. The mechanism by which alcohol worsens HCV related liver disease is not properly understood. One possibility is that alcohol stimulates HCV replication, and the present meta-analysis was performed to examine this issue. Methods: The effect of alcohol on viral titres was assessed in three ways: comparison of the heaviest drinkers with non-drinkers; effect of graded doses of alcohol; and effect of abstinence in the same individual. Results: A total of 14 studies were identified. Comparison of patients with the highest alcohol use with the abstinent group showed a significant association with viral load in three studies, five studies had a positive direction, while the remaining four studies found a negative relationship. Analysis of the combined results showed no association between alcohol consumption and virus levels ( p = 0.29). Assessment of graded doses of alcohol also showed no significant difference between non-drinkers and moderate drinkers ( p = 0.50), between non-drinkers and heavy drinkers ( p = 0.35), or between moderate drinkers and heavy drinkers ( p = 0.32). Five studies examined the influence of abstinence on viral titres but none provided sufficient data for statistical analysis. Conclusions: The present study has failed to show an association between alcohol use and HCV viral titres. These observations raise the possibility that the hepatic damage caused by alcohol and HCV may be purely additive, involving different mechanisms and pathways. C1 Michael E DeBakey VA Med Ctr, Dept Med, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. RP Anand, BS (reprint author), VA Med Ctr, Digest Dis Sect 111D, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM ana0@flash.net NR 32 TC 19 Z9 20 U1 0 U2 1 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 1468 EP 1472 DI 10.1136/gut.2004.056697 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 964JC UT WOS:000231876000024 PM 16162952 ER PT J AU Garner, EIO Feltmate, CM Goldstein, DP Berkowitz, RS AF Garner, EIO Feltmate, CM Goldstein, DP Berkowitz, RS TI The curative effect of a second curettage in persistent trophoblastic disease: A retrospective cohort survey SO GYNECOLOGIC ONCOLOGY LA English DT Editorial Material ID REPEAT UTERINE EVACUATION; HYDATIDIFORM MOLE; MANAGEMENT C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst,New England Trophoblast Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med,Trophoblast Tumor Registry, Dana Farber Canc Inst,Div Gynecol Oncol, Brigham & Womens Hosp,Dept Obstet Gynecol & Repro, Boston, MA 02115 USA. RP Garner, EIO (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dana Farber Canc Inst,New England Trophoblast Dis, 75 Francis Ctr, Boston, MA 02115 USA. EM egarner@partners.org NR 14 TC 12 Z9 13 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 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD OCT PY 2005 VL 99 IS 1 BP 3 EP 5 DI 10.1016/j.ygyno.2005.08.001 PG 3 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 972JE UT WOS:000232449300002 PM 16139344 ER PT J AU Berkenblit, A Matulonis, UA Kroener, JF Dezube, BJ Lam, GN Cuasay, LC Brunner, N Jones, TR Silverman, MH Gold, MA AF Berkenblit, A Matulonis, UA Kroener, JF Dezube, BJ Lam, GN Cuasay, LC Brunner, N Jones, TR Silverman, MH Gold, MA TI angstrom 6, a urokinase plasminogen activator (uPA)-derived peptide in patients with advanced gynecologic cancer: A phase I trial SO GYNECOLOGIC ONCOLOGY LA English DT Article DE urokinase plasminogen activator; gynecologic cancer; pharmacokinetics ID CELL LUNG-CANCER; BREAST-CANCER; OVARIAN-CANCER; INHIBITOR PAI-1; 2ND-LINE CHEMOTHERAPY; PLATINUM-RESISTANT; PROGNOSTIC IMPACT; CLINICAL-TRIALS; POOLED ANALYSIS; BINDING REGION AB Objectives. The aim of this study was to define the toxicity, maximum feasible dose (MFD), and pharmacokinetics (PK) of angstrom 6, a peptide derived from human urokinase plasminogen activator (uPA), in patients with advanced gynecologic cancers, and to explore anti-tumor activity and the effects of angstrom 6 on biomarkers of the urokinase system. Methods. angstrom 6 was administered subcutaneously daily, and doses were escalated in cohorts of three to six subjects. Serial blood specimens were obtained for pharmacokinetics and levels of urokinase plasminogen activator (uPA), uPA receptor (uPAR), and plasminogen activator inhibitor-1 (PAI-1). Results. Sixteen patients were enrolled and eligible for evaluation. No serious drug-related adverse events or dose-limiting toxicity occurred. angstrom 6-related toxicities were limited to grades 1 and 2 adverse effects including local injection site reactions. Five patients had stable tumor measurements for at least 4 cycles, one of whom stayed on study for 12 months. One patient had a confirmed cancer antigen (CA)-125 response (decrease in CA-125 of > 50%) with stable disease on CT scan after 14 cycles and continues on study. Time to peak plasma level of angstrom 6 was 1-2 h. C-max is proportional to dose. The half-life of angstrom 6 was approximately 2 h. Baseline biomarker levels did not predict response and trends over time did not correlate with outcome. Conclusions. angstrom 6 given daily continuously is well tolerated at all dose levels, without any dose-limiting toxicity. Based on the preliminary activity of angstrom 6, a phase II trial is underway in ovarian cancer. (c) 2005 Elsevier Inc. All rights reserved. C1 Beth Israel Deaconess Med Ctr, Dept Med, Div Hematol & Oncol, Boston, MA 02215 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Scripps Canc Ctr, Dept Hematol Oncol, La Jolla, CA 92037 USA. MicroConstants Inc, San Diego, CA 92121 USA. WESTAT Corp, Houston, TX 77005 USA. Royal Vet & Agr Univ, DK-1870 Frederiksberg, Denmark. Angstrom Pharmaceut, San Diego, CA 92121 USA. Harvard Univ, Dana Farber Canc Ctr, Boston, MA 02115 USA. Univ Oklahoma, Hlth Sci Ctr, Gynecol Oncol Sect, Oklahoma City, OK 73190 USA. RP Berkenblit, A (reprint author), Beth Israel Deaconess Med Ctr, Dept Med, Div Hematol & Oncol, Kirstein 106A,330 Brookline Ave, Boston, MA 02215 USA. EM aberkenb@bidmc.harvard.edu NR 32 TC 40 Z9 43 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 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD OCT PY 2005 VL 99 IS 1 BP 50 EP 57 DI 10.1016/j.ygyno.2005.05.023 PG 8 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 972JE UT WOS:000232449300009 PM 16023182 ER PT J AU Fortney, JC Steffick, DE Burgess, JF Maciejewski, ML Petersen, LA AF Fortney, JC Steffick, DE Burgess, JF Maciejewski, ML Petersen, LA TI Are primary care services a substitute or complement for specialty and inpatient services? SO HEALTH SERVICES RESEARCH LA English DT Article; Proceedings Paper CT AcademyHealth Annual Meeting CY JUN, 2004 CL San Diego, CA DE primary care; service substitution; cost; managed care ID INSTRUMENTAL VARIABLES; PREVENTIVE SERVICES; AMBULATORY CARE; UNITED-STATES; MEDICAL-CARE; ACCESS; HOSPITALIZATIONS; OUTCOMES; COSTS; CONTINUITY AB Objective. To determine whether strategies designed to increase members' use of primary care services result in decreases (substitution) or increases (complementation) in the use and cost of other types of health services. Study Setting. Encounter and cost data were extracted from the Department of Veterans Affairs (VA) administrative data sources for the period 1995-1999. This time-frame captures the VA's natural experiment of increasing geographic access to primary care by establishing new satellite primary care clinics, known as Community-Based Outpatient Clinics (CBOCs). Study Design. We exploited this natural experiment to estimate the substitutability of primary care for other health services and its impact on cost. Hypotheses were tested using ordinary least squares (OLS) regression, which was potentially subject to endogeneity bias. Endogeneity bias was assessed using a Hausman test. Endogeneity bias was accounted for by using instrumental variables analysis, which capitalized on the establishment of CBOCs to provide an exogenous identifier (change in travel distance to primary care). Data Collection. Demographic, encounter, and cost data were collected for all veterans using VA health services who resided in the catchment areas of new CBOCs and for a matched group of veterans residing outside CBOC catchment areas. Principal Findings. Change in distance to primary care was a significant and substantial predictor of change in primary care visits. OLS analyses indicated that an increase in primary care service use was associated with increases in the use of all specialty outpatient services and inpatient services, as well as increases in inpatient and outpatient costs. Hausman tests confirmed that OLS results for specialty mental health encounters and mental health admissions were unbiased, but that results for specialty medical encounters, physical health admissions, and outpatient costs were biased. Instrumental variables analyses indicated that an increase in primary care encounters was associated with a decrease in specialty medical encounters and was not associated with an increase in physical health admissions, or outpatient costs. Conclusions. Results provide evidence that health systems can implement strategies to encourage their members to use more primary care services without driving up physical health costs. C1 Cent Arkansas Vet Healthcare Syst, Hlth Serv Res & Dev, Ctr Mental Hlth & Outcomes Res, N Little Rock, AR 72114 USA. Univ Arkansas Med Sci, Coll Med, Dept Psychiat, Div Hlth Serv Res, Little Rock, AR USA. Boston Univ, Sch Publ Hlth, Boston, MA USA. Management Sci Grp, Dept Vet Affairs, Bedford, MA USA. VA Puget Sound Hlth Care Syst, NW Ctr Outcomes Res Older Adults, Hlth Serv Res & Dev, Seattle, WA USA. Univ Washington, Dept Hlth Serv, Seattle, WA USA. Houston Ctr Qual Care & Utilizat Studies, Hlth Serv Res & Dev, Houston VA, Houston, TX USA. Baylor Coll Med, Sect Hlth Serv Res, Houston, TX USA. RP Fortney, JC (reprint author), Cent Arkansas Vet Healthcare Syst, Hlth Serv Res & Dev, Ctr Mental Hlth & Outcomes Res, 2200 Fort Roots Dr, N Little Rock, AR 72114 USA. OI Burgess, James/0000-0002-6646-7071 NR 39 TC 30 Z9 31 U1 4 U2 10 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0017-9124 J9 HEALTH SERV RES JI Health Serv. Res. PD OCT PY 2005 VL 40 IS 5 BP 1422 EP 1442 DI 10.1111/j.1475-6773.2005.00424.x PN 1 PG 21 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 962CG UT WOS:000231708000010 PM 16174141 ER PT J AU Kelly, PA O'Malley, KJ Kallen, MA Ford, ME AF Kelly, PA O'Malley, KJ Kallen, MA Ford, ME TI Integrating validity theory with use of measurement instruments in clinical settings SO HEALTH SERVICES RESEARCH LA English DT Article; Proceedings Paper CT 27th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 12-15, 2004 CL Chicago, IL SP Soc Gen Internal Med DE decision making; measurement; psychometrics; survey research; veterans ID VALIDATION; PSYCHOMETRICS; RELIABILITY; MULTITRAIT; FOCUS AB Objective. To present validity concepts in a conceptual framework useful for research in clinical settings. Principal Findings. We present a three-level decision rubric for validating measurement instruments, to guide health services researchers step-by-step in gathering and evaluating validity evidence within their specific situation. We address construct precision, the capacity of an instrument to measure constructs it purports to measure and differentiate from other, unrelated constructs; quantification precision, the reliability of the instrument; and translation precision, the ability to generalize scores from an instrument across subjects from the same or similar populations. We illustrate with specific examples, such as an approach to validating a measurement instrument for veterans when prior evidence of instrument validity for this population does not exist. Conclusions. Validity should be viewed as a property of the interpretations and uses of scores from an instrument, not of the instrument itself: how scores are used and the consequences of this use are integral to validity. Our advice is to liken validation to building a court case, including discovering evidence, weighing the evidence, and recognizing when the evidence is weak and more evidence is needed. C1 US Dept Vet Affairs, Hlth Serv Res & Dev Serv, METRIC, Houston, TX 77030 USA. Pearson Educ Measurement, Austin, TX USA. Med Univ S Carolina, Dept Biostat Bioinformat & Epidemiol, Charleston, SC 29425 USA. RP Kelly, PA (reprint author), US Dept Vet Affairs, Hlth Serv Res & Dev Serv, METRIC, 2002 Holcombe Blvd 152, Houston, TX 77030 USA. NR 19 TC 7 Z9 7 U1 16 U2 17 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0017-9124 J9 HEALTH SERV RES JI Health Serv. Res. PD OCT PY 2005 VL 40 IS 5 BP 1605 EP 1619 DI 10.1111/j.1475-6773.2005.00445.x PN 2 PG 15 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 964VF UT WOS:000231908400004 PM 16178998 ER PT J AU O'Malley, KJ Cook, KF Price, MD Wildes, KR Hurdle, JF Ashton, CM AF O'Malley, KJ Cook, KF Price, MD Wildes, KR Hurdle, JF Ashton, CM TI Measuring diagnoses: ICD code accuracy SO HEALTH SERVICES RESEARCH LA English DT Article DE ICD codes; accuracy; error sources ID TRANSIENT ISCHEMIC ATTACK; US ADULTS; STROKE; QUALITY; CARE; CLASSIFICATION; RELIABILITY; PATIENT; RECORDS; SYSTEM AB Objective. To examine potential sources of errors at each step of the described inpatient International Classification of Diseases (ICD) coding process. Data Sources/Study Setting. The use of disease codes from the ICD has expanded from classifying morbidity and mortality information for statistical purposes to diverse sets of applications in research, health care policy, and health care finance. By describing a brief history of ICD coding, detailing the process for assigning codes, identifying where errors can be introduced into the process, and reviewing methods for examining code accuracy, we help code users more systematically evaluate code accuracy for their particular applications. Study Design/Methods. We summarize the inpatient ICD diagnostic coding process from patient admission to diagnostic code assignment. We examine potential sources of errors at each step and offer code users a tool for systematically evaluating code accuracy. Principle Findings. Main error sources along the "patient trajectory" include amount and quality of information at admission, communication among patients and providers, the clinician's knowledge and experience with the illness, and the clinician's attention to detail. Main error sources along the "paper trail" include variance in the electronic and written records, coder training and experience, facility quality-control efforts, and unintentional and intentional coder errors, such as misspecification, unbundling, and upcoding. Conclusions. By clearly specifying the code assignment process and heightening their awareness of potential error sources, code users can better evaluate the applicability and limitations of codes for their particular situations. ICD codes can then be used in the most appropriate ways. C1 Pearson Educ Measurement, Austin, TX 78758 USA. Michael E DeBakey VA Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, Houston, TX USA. Houston Ctr Qual Care & Utilizat Studies, Houston, TX USA. Baylor Coll Med, VA Med Ctr, Dept Med, Sect Hlth Serv Res,Michael E DeBakey VA Med Ctr, Houston, TX 77030 USA. VA Salt Lake City Hlth Care Syst, Salt Lake City, UT USA. RP O'Malley, KJ (reprint author), Pearson Educ Measurement, 2201 Donley Dr,Suite 195, Austin, TX 78758 USA. NR 39 TC 248 Z9 251 U1 0 U2 7 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0017-9124 J9 HEALTH SERV RES JI Health Serv. Res. PD OCT PY 2005 VL 40 IS 5 BP 1620 EP 1639 DI 10.1111/j.1475-6773.2005.00444.x PN 2 PG 20 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 964VF UT WOS:000231908400005 PM 16178999 ER PT J AU Ford, ME Kelly, PA AF Ford, ME Kelly, PA TI Conceptualizing and categorizing race and ethnicity in health services research SO HEALTH SERVICES RESEARCH LA English DT Article DE race and ethnicity; measurement; health disparities ID PUBLIC-HEALTH; ACCULTURATION SCALE; UNITED-STATES; 2000 CENSUS; US CENSUS; RACE/ETHNICITY; HISPANICS; COMMUNITY; RACISM; DISCRIMINATION AB Objectives. Veterans Affairs (VA) patient populations are becoming increasingly diverse in race and ethnicity. The purpose of this paper is to (1) document the importance of using consistent standards of conceptualizing and categorizing race and ethnicity in health services research, (2) provide an overview of different methods currently used to assess race and ethnicity in health services research, and (3) suggest assessment methods that could be incorporated into health services research to ensure accurate assessment of disease prevalence and incidence, as well as accounts of appropriate health services use, in patients with different racial and ethnic backgrounds. Design. A critical review of published literature was used. Principal Findings. Race is a complex, multidimensional construct. For some individuals, institutionalized racism and internalized racism are intertwined in the effects of race on health outcomes and health services use. Ethnicity is most commonly used as a social-political construct and includes shared origin, shared language, and shared cultural traditions. Acculturation appears to affect the strength of the relationships among ethnicity, health outcomes, and health services use. Conclusion. Improved and consistent methods of data collection need to be developed for use by VA researchers across the country. VA research sites with patients representing specific population groups could use a core set of demographic items in addition to expanded modules designed to assess the ethnic diversity within these population groups. Improved and consistent methods of data collection could result in the collection of higher-quality data, which could lead to the identification of race- and ethnic-specific health services needs. These investigations could in turn lead to the development of interventions designed to reduce or eliminate these disparities. C1 Med Univ S Carolina, Dept Biostat Bioinformat & Epidemiol, Charleston, SC 29425 USA. US Dept Vet Affairs, METRIC, Hlth Serv Res & Dev Serv, Houston, TX USA. RP Ford, ME (reprint author), Med Univ S Carolina, Dept Biostat Bioinformat & Epidemiol, 135 Cannon St,Suite 303,POB 250835, Charleston, SC 29425 USA. FU NIA NIH HHS [1 P30 AG 21677, P30 AG021677] NR 47 TC 40 Z9 40 U1 1 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0017-9124 J9 HEALTH SERV RES JI Health Serv. Res. PD OCT PY 2005 VL 40 IS 5 BP 1658 EP 1675 DI 10.1111/j.1475-6773.2005.00449.x PN 2 PG 18 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 964VF UT WOS:000231908400007 PM 16179001 ER PT J AU Whary, MT Sundina, N Nagler-Anderson, C Nambiar, PR Fox, JG AF Whary, MT Sundina, N Nagler-Anderson, C Nambiar, PR Fox, JG TI Heligmosomoides polygyrus parasitism attenuates the progression of typhlocolitis, epithelial hyperplasia, and dysplasia in the IL-10-/- mouse model of Helicobacter hepaticus-associated inflammatory bowel disease SO HELICOBACTER LA English DT Meeting Abstract CT 18th International Workshop on Gastrointestinal Pathology and Helicobactor CY OCT 12-14, 2005 CL Copenhagen, DENMARK SP European Helicobacter Study Grp C1 MIT, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1083-4389 J9 HELICOBACTER JI Helicobacter PD OCT PY 2005 VL 10 IS 5 BP 492 EP 492 PG 1 WC Gastroenterology & Hepatology; Microbiology SC Gastroenterology & Hepatology; Microbiology GA 965LK UT WOS:000231951800119 ER PT J AU Imamura, S Mitsufuji, S Shiomi, S Yamaoka, Y Tachibana, S Kato, N Fukumoto, K Sumida, Y Kanemasa, K Konishi, H Okanoue, T AF Imamura, S Mitsufuji, S Shiomi, S Yamaoka, Y Tachibana, S Kato, N Fukumoto, K Sumida, Y Kanemasa, K Konishi, H Okanoue, T TI Helicobacter pylori infection protects against pollen allergy SO HELICOBACTER LA English DT Meeting Abstract CT 18th International Workshop on Gastrointestinal Pathology and Helicobactor CY OCT 12-14, 2005 CL Copenhagen, DENMARK SP European Helicobacter Study Grp C1 Nara City Hosp, Nara, Japan. Kyoto Prefectural Univ Med, Grad Sch Med Sci, Kyoto, Japan. Michael E DeBakey Vet Affairs Med Ctr, Dept Med, Houston, TX USA. Baylor Coll Med, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1083-4389 J9 HELICOBACTER JI Helicobacter PD OCT PY 2005 VL 10 IS 5 BP 512 EP 512 PG 1 WC Gastroenterology & Hepatology; Microbiology SC Gastroenterology & Hepatology; Microbiology GA 965LK UT WOS:000231951800174 ER PT J AU Behari, J Swaminathan, V Bryce, C Cacciarelli, TV Shakil, OA Ahmad, J AF Behari, J Swaminathan, V Bryce, C Cacciarelli, TV Shakil, OA Ahmad, J TI Racial differences in model for end-stage liver disease (MELD) scores, change in meld (DELTA MELD) on the transplant list, and waiting times of liver transplant recipients 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 Univ Pittsburgh, Pittsburgh, PA 15260 USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA 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 205A EP 205A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 972VC UT WOS:000232480300024 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 Hiasa, Y Tokumoto, Y Yamanaka, S Konishi, I Sera, T Horiike, N Chung, RT Onji, M AF Hiasa, Y Tokumoto, Y Yamanaka, S Konishi, I Sera, T Horiike, N Chung, RT Onji, M TI ME3738 effectively reduces HCV replication in a binary replication model 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 Ehime Univ, Sch Med, Dept Internal Med 3, Matsuyama, Ehime 790, Japan. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 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 248A EP 248A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 972VC UT WOS:000232480300129 ER PT J AU Haller, A Lauer, G Parker, J King, T Lu, YN Kemmler, C Bellgrau, D Franzusoff, A Rodell, T Apelian, D Duke, R AF Haller, A Lauer, G Parker, J King, T Lu, YN Kemmler, C Bellgrau, D Franzusoff, A Rodell, T Apelian, D Duke, R TI Whole recombinant yeast-based immunotherapy for treatment of chronic hepatitis C infection induces dose-dependent T cell responses and therapeutic effects without vector neutralization 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 Globelmmune Inc, Aurora, CO USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr, Cambridge, MA 02138 USA. Globelmmune Inc, Aurora, CO 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 249A EP 249A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 972VC UT WOS:000232480300131 ER PT J AU Servoss, JC Campos, NG Salomon, JA Freedberg, KA Samet, JH Goldie, SJ Chung, RT AF Servoss, JC Campos, NG Salomon, JA Freedberg, KA Samet, JH Goldie, SJ Chung, RT TI Cost-effectiveness of treatment for chronic hepatitis C infection in patients coinfected with human immunodeficiency virus 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 Massachusetts Gen Hosp, GI Unit, Boston, MA USA. Harvard Univ Initiat Global Hlth, Cambridge, MA USA. Boston Med Ctr, Boston, MA USA. RI Salomon, Joshua/D-3898-2009 OI Salomon, Joshua/0000-0003-3929-5515 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 350A EP 350A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 972VC UT WOS:000232480300385 ER PT J AU Kanwal, F Farid, M Martin, P Chen, G Gralnek, IM Dulai, GS Spiegel, BM AF Kanwal, F Farid, M Martin, P Chen, G Gralnek, IM Dulai, GS Spiegel, BM TI Treatment alternatives for hepatitis B cirrhosis: A cost-effectiveness analysis 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 W Los Angeles VA, Los Angeles, CA USA. Greater Los Angeles Healthcare Syst W LA, Los Angeles, CA USA. Mt Sinai Sch Med, New York, NY USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 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 351A EP 351A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 972VC UT WOS:000232480300388 ER PT J AU Kamegaya, Y Sarracino, D Krastins, B Blackard, JT Lin, WY Chung, RT AF Kamegaya, Y Sarracino, D Krastins, B Blackard, JT Lin, WY Chung, RT TI Identification of candidate biomarkers for detection of hepatocellular carcinoma using a novel proteomic 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 Harvard Partners Ctr Genet & Gen, Cambridge, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2005 VL 42 IS 4 SU 1 BP 394A EP 394A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 972VC UT WOS:000232480301043 ER PT J AU Anand, BS DeBakey, ME Currie, S Bini, EJ Shen, H Ho, SB Dieperink, E Wright, TL AF Anand, BS DeBakey, ME Currie, S Bini, EJ Shen, H Ho, SB Dieperink, E Wright, TL TI Alcohol use in US veterans: A multicenter study of 4,061 hepatitis C-infected 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 Michael E DeBakey VA Med Ctr, Houston, TX USA. San Francisco VA Med Ctr, San Francisco, CA USA. VA New York Harbor Healthcare Syst, New York, NY USA. San Francisco VA Med Ctr, San Francisco, CA USA. Mineapolis VA Med Ctr, Minneapolis, MN USA. San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 EI 1527-3350 J9 HEPATOLOGY JI Hepatology PD OCT PY 2005 VL 42 IS 4 SU 1 BP 423A EP 423A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 972VC UT WOS:000232480301118 ER PT J AU Butt, AA Skanderson, M McGinnis, K Ahuja, T Bryce, C Barnato, A Chang, CCH AF Butt, AA Skanderson, M McGinnis, K Ahuja, T Bryce, C Barnato, A Chang, CCH TI Impact of hepatitis C virus infection and other comorbidities on survival in patients on dialysis 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 Pittsburgh, Pittsburgh, PA USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. Univ Texas, Med Branch Galveston, Galveston, TX 77555 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 430A EP 430A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 972VC UT WOS:000232480301134 ER PT J AU Khokhar, A Farnan, R MacFarlane, C Bacon, B McHutchison, J Afdhal, N AF Khokhar, A Farnan, R MacFarlane, C Bacon, B McHutchison, J Afdhal, N TI Liver stiffness and biomarkers: Correlation with cirrhosis, portal hypertension and hepatic synthetic function 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 BIDMC, Boston, MA USA. SLU, St Louis, MO USA. Duke Univ, Med Ctr, Durham, NC USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 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 433A EP 433A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 972VC UT WOS:000232480301142 ER PT J AU Hoyumpa, A Sharkey, FE Brock, PS Page, RT Brock, PS Kashi, MR Herrera, AM Smith, W Poy, IG Webb, AL Ali, O AF Hoyumpa, A Sharkey, FE Brock, PS Page, RT Brock, PS Kashi, MR Herrera, AM Smith, W Poy, IG Webb, AL Ali, O TI Greater prevalence of cirrhosis in Hispanics than in Caucasians or African Americans 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 Texas, Ctr Hlth Sci, San Antonio, TX 78285 USA. Univ Texas, Phys Grp, San Antonio, TX 78285 USA. S Texas Vet Hlth Care Syst, Audie Murphy Div, San Antonio, TX USA. NR 0 TC 4 Z9 4 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 442A EP 442A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 972VC UT WOS:000232480301163 ER PT J AU Soule, JL Olyaei, A Schwartz, M Rosen, HR Ham, JM Orloff, SL AF Soule, JL Olyaei, A Schwartz, M Rosen, HR Ham, JM Orloff, SL TI Recurrent hepatitis C is a risk factor for poor outcome after liver retransplantation 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 Oregon Hlth & Sci Univ, Portland, OR USA. Portland VA Med Ctr, Portland, OR 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 484A EP 485A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 972VC UT WOS:000232480301274 ER PT J AU Chang, SYP Chan, JP Santini, CD Sigua, CL Hu, XL Yee, L Li, HZ Wright, TL Sninsky, JJ AF Chang, SYP Chan, JP Santini, CD Sigua, CL Hu, XL Yee, L Li, HZ Wright, TL Sninsky, JJ TI Predictive value of gene expression of host factors at 12-weeks of pegylated interferon-alpha plus ribavirin treatment in hepatitis C 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 Celera Diagnost, Alameda, CA USA. San Francisco VA Med Ctr, San Francisco, CA USA. Univ Penn, Sch Med, Philadelphia, PA 19104 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 520A EP 520A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 972VC UT WOS:000232480301368 ER PT J AU Lin, WY Choe, H Kamegaya, Y Blackard, JT Kim, SS Agrawal, S Walewski, JL Xavier, RJ Branch, A Chun, RT AF Lin, WY Choe, H Kamegaya, Y Blackard, JT Kim, SS Agrawal, S Walewski, JL Xavier, RJ Branch, A Chun, RT TI HCV upregulates TGF-b1 expression in several models of HCV replication 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 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. Mt Sinai Sch Med, New York, NY 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 527A EP 528A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 972VC UT WOS:000232480301387 ER PT J AU Lin, WY Blackard, JT Kamegaya, Y Kim, SS Chung, RT AF Lin, WY Blackard, JT Kamegaya, Y Kim, SS Chung, RT TI The N-terminal of HCV core protein degrades STAT1 and blocks IFN signal transduction 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 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 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 545A EP 546A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 972VC UT WOS:000232480301429 ER PT J AU Bonkovsky, HL Di Bisceglie, AM Morishima, C Chung, RT Everson, GT Ghany, MG Hoofnagle, JH Lindsay, KL Hoefs, JC Lee, WM Lok, AS Shiffman, ML Wright, EC AF Bonkovsky, HL Di Bisceglie, AM Morishima, C Chung, RT Everson, GT Ghany, MG Hoofnagle, JH Lindsay, KL Hoefs, JC Lee, WM Lok, AS Shiffman, ML Wright, EC TI Iron and HFE gene mutations in advanced chronic hepatitis C (CHC): Results from the lead-in phase of the HALT-C trial 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 Connecticut, Ctr Hlth, Farmington, CT USA. St Louis Univ, St Louis, MO 63103 USA. Univ Washington, Seattle, WA 98195 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Colorado, Ctr Hlth Sci, Denver, CO USA. NIDDKD, Bethesda, MD 20892 USA. Univ So Calif, Los Angeles, CA 90089 USA. Univ Calif Irvine, Irvine, CA USA. Univ Texas, SW Med Ctr, Dallas, TX USA. Univ Michigan, Med Ctr, Ann Arbor, MI USA. Virginia Commonwealth Univ, Hlth Syst, Richmond, VA USA. New England Res Inst, Watertown, MA 02172 USA. RI Lok, Anna /B-8292-2009 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 548A EP 548A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 972VC UT WOS:000232480301435 ER PT J AU Tokumoto, Y Hiasa, Y Konishi, I Sera, T Michitaka, K Horiike, N Chung, RT Onji, M AF Tokumoto, Y Hiasa, Y Konishi, I Sera, T Michitaka, K Horiike, N Chung, RT Onji, M TI Expression of HCV is regulated by PKR 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 Ehime Univ, Sch Med, Dept Internal Med 3, Toonshi, Japan. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2005 VL 42 IS 4 SU 1 BP 551A EP 552A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 972VC UT WOS:000232480301444 ER PT J AU Ebinuma, H Li, Y Valiga, M Chan, KM AF Ebinuma, H Li, Y Valiga, M Chan, KM TI HCV persistence is associated with impaired proliferative function of CD25-negative CD4 T cell subset 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. Philadelphia VA Med Ctr, Philadelphia, PA 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 556A EP 556A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 972VC UT WOS:000232480301456 ER PT J AU Walewski, JL Lin, WY Wen, F Schwartz, M Schmidt, W Chung, R Branch, AD AF Walewski, JL Lin, WY Wen, F Schwartz, M Schmidt, W Chung, R Branch, AD TI HCV up-regulates TGF beta 1 and affects its pathway members in HCV-infected human livers and model systems 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 Mt Sinai Sch Med, New York, NY USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Iowa, Dept Med, Iowa City, IA 52242 USA. Mt Sinai Hosp, Dept Surg, New York, NY USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2005 VL 42 IS 4 SU 1 BP 566A EP 566A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 972VC UT WOS:000232480301482 ER PT J AU Lieber, CS Leo, MA Cao, Q Mak, KM Ren, CL Ponomarenko, A Wang, XL DeCarli, LM AF Lieber, CS Leo, MA Cao, Q Mak, KM Ren, CL Ponomarenko, A Wang, XL DeCarli, LM TI Detrimental effects of medium-chain triglycerides (MCT) in nonalcoholic steatohepatitis (NASH): Contrast with their beneficial action in alcoholic liver disease 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 Mt Sinai Sch Med, Bronx, NY USA. Bronx Vet Adm Med Ctr, Bronx, NY 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 570A EP 570A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 972VC UT WOS:000232480302010 ER PT J AU Wu, Y Imai, M Sun, XF Csizmadia, E Enjyoji, K Choi, CH Robson, SC Usheva, A AF Wu, Y Imai, M Sun, XF Csizmadia, E Enjyoji, K Choi, CH Robson, SC Usheva, A TI Transcription factor YY1 and the retinoblastoma protein are downstream targets of CD39/ENTPD1 signaling pathways during liver regeneration 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 Harvard Univ, Sch Med, BIDMC, Boston, MA 02115 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 642A EP 643A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 972VC UT WOS:000232480302194 ER PT J AU Wu, Y Sun, XF Imai, M Sultan, B Csizmadia, E Enjyoji, K Jackson, SW Usheva, A Robson, SC AF Wu, Y Sun, XF Imai, M Sultan, B Csizmadia, E Enjyoji, K Jackson, SW Usheva, A Robson, SC TI Modulation of RAS/ERK signaling by CD39/ENTPD1 during liver regeneration 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 Harvard Univ, Sch Med, BIDMC, Boston, MA 02115 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 643A EP 643A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 972VC UT WOS:000232480302196 ER PT J AU Bini, EJ Anand, BS Aytaman, A Samanta, A Cordoba-Rellosa, I Nemchausky, B Trevino, HH Mah'moud, MA Weston, AP Pimstone, NR Stancic, S Chang, KM AF Bini, EJ Anand, BS Aytaman, A Samanta, A Cordoba-Rellosa, I Nemchausky, B Trevino, HH Mah'moud, MA Weston, AP Pimstone, NR Stancic, S Chang, KM TI Glucose-6-phosphate dehydrogenase deficiency is associated with severe anemia during interferon and ribavirin therapy 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 VA New York Harbor Healthcare Syst, New York, NY USA. NYU, Sch Med, New York, NY USA. Houston VAMC, Houston, TX USA. VA New York Harbor Healthcare Syst, Brooklyn, NY USA. E Orange VAMC, E Orange, NJ USA. Hines VAMC, Hines, IL USA. San Antonio VAMC, San Antonio, TX USA. VAMC, Columbia, SC USA. VAMC, Kansas City, MO USA. VAMC, Mather, CA USA. VAMC, Hudson Valley, NY USA. VAMC, Philadelphia, PA USA. NR 0 TC 1 Z9 1 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 648A EP 648A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 972VC UT WOS:000232480302209 ER PT J AU Naqvi, Z Eldeiry, L Brau, N Rosman, AS Greenberg, PD AF Naqvi, Z Eldeiry, L Brau, N Rosman, AS Greenberg, PD TI Reduction in hemoglobin A1c values in diabetic patients during hepatitis C combination therapy: A combined effect of ribavirin-induced hemolysis and decreased glucose levels 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 Bronx Vet Adm Med Ctr, Bronx, NY USA. Bronx Vet Adm Med Ctr, Bronx, NY 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 662A EP 662A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 972VC UT WOS:000232480302242 ER PT J AU Huckans, MS Loftis, JM Hauser, P AF Huckans, MS Loftis, JM Hauser, P TI Interferon therapy completion and response rates for hepatitis C among patients with schizophrenia, schizoaffective disorder, and substance use disorders 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 Portland VA Med Ctr, Portland, OR USA. Oregon Hlth & Sci Univ, Portland, OR USA. Portland VA Med Ctr, Portland, OR 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 665A EP 665A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 972VC UT WOS:000232480302250 ER PT J AU Lieber, CS Anand, BS Bini, EJ Leo, MA Lowe, N Murthy, U Paronetto, F Schiff, E Simon, D AF Lieber, CS Anand, BS Bini, EJ Leo, MA Lowe, N Murthy, U Paronetto, F Schiff, E Simon, D TI Polyenylphosphatidylcholine (PPC) is beneficial for the treatment of hepatitis C 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 Mt Sinai Sch Med, Bronx, NY USA. Bronx Vet Adm Med Ctr, Bronx, NY USA. Baylor Coll Med, Med Ctr, Houston, TX 77030 USA. VA New York Harbor Healthcare Syst, New York, NY USA. Syracuse VA Med Ctr, Syracuse, NY USA. Univ Miami, Miami, FL 33152 USA. Jacobi Med Ctr, Bronx, NY 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 695A EP 695A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 972VC UT WOS:000232480302320 ER PT J AU Lai, M Hyatt, B Afdhal, N AF Lai, M Hyatt, B Afdhal, N TI Role of liver biopsy in patients with normal ALT and high HBV DNA 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 BIDMC, Boston, MA USA. NR 0 TC 14 Z9 19 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 720A EP 720A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 972VC UT WOS:000232480302380 ER PT J AU Cao, Q Mak, KM Lieber, CS AF Cao, Q Mak, KM Lieber, CS TI Leptin represses matrix metalloproteinase (MMP)-1 gene expression in human hepatic stellate cells which contributes to its fibrogenic effect 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 Mt Sinai Sch Med, Bronx, NY USA. Bronx Vet Adm Med Ctr, Bronx, NY 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 731A EP 732A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 972VC UT WOS:000232480302411 ER PT J AU Deng, QG She, HY Cheng, JH French, SW Koop, DR Xiong, SG Tsukamoto, H AF Deng, QG She, HY Cheng, JH French, SW Koop, DR Xiong, SG Tsukamoto, H TI Steatohepatitis induced by intragastric overfeeding in mice SO HEPATOLOGY LA English DT Article ID NECROSIS-FACTOR-ALPHA; HEPATIC CYTOCHROME-P450 2E1; ACTIVATED PROTEIN-KINASE; INDUCED LIVER-INJURY; INSULIN-RESISTANCE; NONALCOHOLIC STEATOHEPATITIS; LEPTIN RECEPTOR; FATTY LIVER; GENE-EXPRESSION; X-RECEPTORS AB Nonalcoholic steatoliepatitis is prevalent among obese individuals with excessive caloric intake, insulin resistance, and type 11 diabetes. However, no animal models exist that recapitulate this important association. This study produced and characterized steatoliepatitis (SH) caused by intragastric overfeeding in mice. C57BL/6, tumor necrosis factor (TNF) type 1 receptor-deficient, and genetically matched wild type mice were fed via an implanted gastrostomy tube a high-fat diet for 9 weeks in the increasing amount up to 85% in excess of the standard intake. Animals were examined for weight gain, insulin sensitivity, and histology and biochemistry of liver and white adipose tissue (WAT). Overfed C57BL/6 mice progressively became obese, with 71% larger final body weights. They had increased visceral WAT, hyperglycemia, hyperinsulinemia, hyperleptinemia, glucose intolerance, and insulin resistance. Of these mice, 46% developed SH with increased plasma alanine aminotransferase (121 +/- 27 vs. 13 +/- 1 U/L), neutrophilic infiltration, and sinusoidal and pericellular fibrosis. Obese WAT showed increased TNF alpha and leptin expression and reciprocally reduced adiponectin expression. The expression of lipogenic transcription factors (SREBP-1c, PPAR gamma, LXR alpha) was increased, whereas that of a lipolytic nuclear factor PPAR alpha was reduced in SH. SH was associated with reduced cytochrome P450 (Cyp)2el but increased Cyp4a. TNF type 1 receptor deficiency did not prevent obesity and SH. In conclusion, forced overfeeding with a high-fat diet in mice induces obesity, insulin resistance, and SH in the absence of TNF signaling or Cyp2e1 induction. C1 Univ So Calif, Keck Sch Med, Res Ctr Alcohol Liver & Pancreat Dis, Los Angeles, CA USA. Univ So Calif, Keck Sch Med, Dept Pathol, Los Angeles, CA USA. Harbor UCLA Med Ctr, Ctr Med, Torrance, CA 90509 USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Tsukamoto, H (reprint author), 1333 San Pablo St,MMR-412, Los Angeles, CA 90033 USA. EM htsukamo@usc.edu FU NIAAA NIH HHS [R37 AA006603, P50 AA11999] NR 50 TC 146 Z9 150 U1 0 U2 6 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 BP 905 EP 914 DI 10.1002/hep.20877 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 970XB UT WOS:000232344600020 PM 16175602 ER PT J AU Ueki, K Kadowaki, T Kahn, CR AF Ueki, K Kadowaki, T Kahn, CR TI Role of suppressors of cytokine signaling SOCS-1 and SOCS-3 in hepatic steatosis and the metabolic syndrome SO HEPATOLOGY RESEARCH LA English DT Article; Proceedings Paper CT 3rd Annual Single Topic Conference on Nonalcoholic Steatohepatitis in Asia-Oceania CY 2005 CL Kochi, JAPAN SP Japan Soc Hepatol, Ajinomoto Pharma Co Ltd, F Hoffmann-La Roch Ltd, GlaxoSmithKline K K, Mitsubishi Pharma Co DE adipokine; metabolic syndrome; insulin resistance; SREBP-1c; SOCS ID INSULIN-RESISTANCE; ADIPOSE-TISSUE; PROTEINS; LIVER; MICE AB Insulin resistance, obesity, diabetes, dyslipidemia and nonalcoholic fatty liver are components of the metabolic syndrome, a disease complex that is increasing at epidemic rates in westernized countries. Although proinflaniniatory cytokines have been Suggested to contribute to the development of these disorders, the Molecular mechanism of the development of this syndrome is poorly understood. In this study, we show that expression of suppressor of cytokine signaling SOCS-1 and SOCS-3 is increased in livers of obese insulin-resistant animals, and that adenoviral-mediated overexpression of SOCS-1 or SOCS-3 in liver causes insulin resistance through down-regulation of tyrosine phosphorylation Of insulin receptor substrate (IRS) proteins. Moreover, the increased SOCS-1 and SOCS-3 also cause a prominent up-regulation of the key regulator of fatty acid synthesis in liver, sterol regulatory element binding protein (SREBP)-1. Conversely, inhibition of SOCS-1 and SOCS-3 in livers of obese diabetic dbldb mice by antisense treatment modestly improves insulin sensitivity, but completely normalizes the increased expression of SREBP-1. The latter leads to dramatic amelioration of hepatic steatosis and hypertriglyceridemia. Promoter activity analysis reveals that expression of SOCS-1 or SOCS-3 with SOCS-3 being more potent enhances SREBP-1c expression, while it is inhibited by expression of STAT3. This STAT3-mediated inhibition of SREBP-1c expression is antagonized by co-expression of SOCS proteins. Moreover, db/db mice display decreased STAT3 phosphorylation in liver that is normalized by antisense treatment of SOCS proteins. These data Suggest that obese Subjects in the persistent inflammatory states, Such as elevated circulating tumor necrosis factor-alpha, may have down-regulated STAT3-mediated signaling by increased SOCS proteins, leading to up-regulation of SREBP-1c expression and increased fatty acid synthesis in liver. Thus, SOCS proteins play an important role in pathogenesis of the metabolic syndrome by concordantly modulating cytokine signaling and insulin signaling. (c) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Univ Tokyo, Grad Sch Med, Dept Metab Dis, Bunkyo Ku, Tokyo 1138655, Japan. Harvard Univ, Sch Med, Div Res, Joslin Diabet Ctr, Boston, MA USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Ueki, K (reprint author), Univ Tokyo, Grad Sch Med, Dept Metab Dis, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1138655, Japan. EM ueki-tky@umin.ac.jp NR 11 TC 54 Z9 64 U1 0 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1386-6346 J9 HEPATOL RES JI Hepatol. Res. PD OCT PY 2005 VL 33 IS 2 BP 185 EP 192 DI 10.1016/j.hepres.2005.09.032 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 994PM UT WOS:000234043700028 PM 16226915 ER PT J AU Seong, IS Ivanova, E Lee, JM Choo, YS Fossale, E Anderson, M Gusella, JF Laramie, JM Myers, RH Lesort, M MacDonald, ME AF Seong, IS Ivanova, E Lee, JM Choo, YS Fossale, E Anderson, M Gusella, JF Laramie, JM Myers, RH Lesort, M MacDonald, ME TI HD CAG repeat implicates a dominant property of huntingtin in mitochondrial energy metabolism SO HUMAN MOLECULAR GENETICS LA English DT Article ID ADENINE-NUCLEOTIDE TRANSLOCASE; ASPARTATE RECEPTOR ACTIVATION; MEDIUM SPINY NEURONS; KNOCK-IN MICE; CELL-DEATH; PERMEABILITY TRANSITION; STRIATAL CELLS; 3-NITROPROPIONIC ACID; DISEASE LYMPHOBLASTS; APOPTOTIC PATHWAY AB The 'expanded' HD CAG repeat that causes Huntington's disease (HD) encodes a polyglutamine tract in huntingtin, which first targets the death of medium-sized spiny striatal neurons. Mitochondrial energetics, related to N-methyl-d-aspartate (NMDA) Ca2+-signaling, has long been implicated in this neuronal specificity, implying an integral role for huntingtin in mitochondrial energy metabolism. As a genetic test of this hypothesis, we have looked for a relationship between the length of the HD CAG repeat, expressed in endogenous huntingtin, and mitochondrial ATP production. In STHdh(Q111) knock-in striatal cells, a juvenile onset HD CAG repeat was associated with low mitochondrial ATP and decreased mitochondrial ADP-uptake. This metabolic inhibition was associated with enhanced Ca2+-influx through NMDA receptors, which when blocked resulted in increased cellular [ATP/ADP]. We then evaluated [ATP/ADP] in 40 human lymphoblastoid cell lines, bearing non-HD CAG lengths (9-34 units) or HD-causing alleles (35-70 units). This analysis revealed an inverse association with the longer of the two allelic HD CAG repeats in both the non-HD and HD ranges. Thus, the polyglutamine tract in huntingtin appears to regulate mitochondrial ADP-phosphorylation in a Ca2+-dependent process that fulfills the genetic criteria for the HD trigger of pathogenesis, and it thereby determines a fundamental biological parameter-cellular energy status, which may contribute to the exquisite vulnerability of striatal neurons in HD. Moreover, the evidence that this polymorphism can determine energy status in the non-HD range suggests that it should be tested as a potential physiological modifier in both health and disease. C1 Massachusetts Gen Hosp, Ctr Human Genet Res, Mol Neurogenet Unit, Richard B Simches Res Ctr, Boston, MA 02114 USA. Univ Alabama, Dept Psychiat, Birmingham, AL 35294 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. RP MacDonald, ME (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Mol Neurogenet Unit, Richard B Simches Res Ctr, 185 Cambridge St, Boston, MA 02114 USA. EM macdonam@helix.mgh.harvard.edu OI Myers, Richard/0000-0002-8365-2674 FU NINDS NIH HHS [NS16367, NS32765, NS41552, R01 NS041552, R01 NS041552-04] NR 58 TC 162 Z9 164 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD OCT 1 PY 2005 VL 14 IS 19 BP 2871 EP 2880 DI 10.1093/hmg/ddi319 PG 10 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 965AV UT WOS:000231923000010 PM 16115812 ER PT J AU Brewer, KC Mwizerva, O Goldstein, AM AF Brewer, KC Mwizerva, O Goldstein, AM TI BMPRIA is a promising marker for evaluating ganglion cells in the enteric nervous system - a pilot study SO HUMAN PATHOLOGY LA English DT Article DE enteric nervous system; bone morphogenetic proteins; Hirschsprung disease; intestinal neuronal dysplasia; BMPRIA ID HIRSCHSPRUNGS-DISEASE; GUT; MIGRATION; DIFFERENTIATION; EXPRESSION; DISORDERS; DIAGNOSIS AB Congenital disorders of the enteric nervous system (ENS) comprise a large group of conditions characterized by abnormalities in the number, size, or location of enteric ganglia. Their diagnosis requires careful histological evaluation of intestinal biopsies to determine the presence and morphology of these cells. Based on the recently discovered role of bone morphogenetic proteins (BMPs) in ENS development, we examined the expression of the ligands, BMP2 and BMP4, and their receptors, BMPRIA, BMPRIB, and BMPRII, during formation of the human ENS. The spatiotemporal expression pattern of these proteins suggests a role for BMP signaling in human ENS formation. We find BMPRIA, in particular, strongly and specifically expressed in all ganglion cells of the ENS at every age examined, from fetus to adult. Moreover, BMPRIA immumohistochemistry consistently allowed the identification of ganglion cells in rectal biopsies from patients with Hirschsprung disease, intestinal neuronal dysplasia, and immature ganglion cells. We propose that BMPRIA immunohistochemistry may be a promising new tool for the identification of enteric ganglion cells in the evaluation of patients with neurointestinal disorders. (c) 2005 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pediat Surg, Boston, MA 02114 USA. RP Goldstein, AM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pediat Surg, Boston, MA 02114 USA. EM agoldstein@partners.org FU NICHD NIH HHS [1 K08 HD46655-01] NR 24 TC 14 Z9 15 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD OCT PY 2005 VL 36 IS 10 BP 1120 EP 1126 DI 10.1016/j.humpath.2005.08.006 PG 7 WC Pathology SC Pathology GA 977TH UT WOS:000232825600012 PM 16226113 ER PT J AU Lloyd-Jones, DM Sutton-Tyrrell, K Patel, AS Matthews, KA Pasternak, RC Everson-Rose, SA Scuteri, A Chae, CU AF Lloyd-Jones, DM Sutton-Tyrrell, K Patel, AS Matthews, KA Pasternak, RC Everson-Rose, SA Scuteri, A Chae, CU TI Ethnic variation in hypertension among premenopausal and perimenopausal women - Study of women's health across the nation SO HYPERTENSION LA English DT Article DE blood pressure; ethnicity; antihypertensive agents ID BODY-MASS INDEX; NUTRITION EXAMINATION SURVEY; NORMAL BLOOD-PRESSURE; WAIST-HIP RATIO; RISK-FACTORS; CIRCUMFERENCE; PREVALENCE; ADULTS; POPULATION; PREVENTION AB Data are sparse regarding hypertension prevalence, treatment, and control among some ethnic groups of American women. Furthermore, the effects of ethnicity on hypertension, independent of other factors that vary with ethnicity, are poorly understood. We examined the prevalence of hypertension (defined as systolic >= 140 or diastolic >= 90 mm Hg or receiving treatment), treatment, and control (to < 140/< 90 mm Hg) in a multiethnic study of premenopausal and perimenopausal women. Stepwise multivariable logistic regression was used to select covariates associated with hypertension. Among 3292 women, 46.9% were white, 28.3% were black, 8.7% were Hispanic, 7.6% were Chinese, and 8.5% were Japanese. Among these 5 ethnic groups, respectively, there was substantial variation in prevalence of normal blood pressure levels (<120/<80 mm Hg; 59.9%, 35.4%, 16.8%, 67.2%, and 63.7%) and hypertension (14.5%, 38.1%, 27.6%, 12.8%, and 11.0%). After multivariable adjustment, hypertension prevalence was 2 to 3 X higher among black and Hispanic women but similar among Chinese and Japanese women compared with white women. Among hypertensive participants, prevalence of anti hypertensive treatment was highest among blacks (58.9%) and whites (55.2%) and lowest among Chinese (34.4%). Prevalence of control to goal blood pressure levels was highest among whites (43.0%) and Japanese (38.7%) and markedly lower among Hispanic women (11.4%). Compared with whites, black and Hispanic women have significantly higher prevalence of hypertension independent of other factors, whereas Chinese and Japanese women have similar prevalence. Treatment and control rates vary considerably across ethnicities. Greater efforts must be made to improve hypertension awareness, treatment, and control in all middle-aged women, particularly those in ethnic minority groups. C1 Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. Northwestern Univ, Feinberg Sch Med, Div Cardiol, Chicago, IL 60611 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Rush Univ, Med Ctr, Chicago, IL 60612 USA. NIH, Bethesda, MD 20892 USA. RP Lloyd-Jones, DM (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, 680 N Lake Shore Dr,Suite 1102, Chicago, IL 60611 USA. EM dlj@northwestern.edu RI Lloyd-Jones, Donald/C-5899-2009 NR 25 TC 17 Z9 17 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD OCT PY 2005 VL 46 IS 4 BP 689 EP 695 DI 10.1161/01.HYP.0000182659.03194.db PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 973YR UT WOS:000232559000012 PM 16144985 ER PT J AU Soubret, A Ripoll, J Ntziachristos, V AF Soubret, A Ripoll, J Ntziachristos, V TI Accuracy of fluorescent tomography in the presence of heterogeneities: Study of the normalized born ratio SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE absorption; diffusion theory; fluorescence tomography; molecular imaging ID DIFFUSE OPTICAL TOMOGRAPHY; PHOTON MIGRATION MEASUREMENTS; IMAGE-RECONSTRUCTION; TURBID MEDIA; BOUNDARY-CONDITIONS; RADIATIVE-TRANSFER; SCATTERING MEDIA; TISSUE; LIGHT; EQUATION AB We studied the performance of three-dimensional fluorescence tomography of diffuse media in the presence of heterogeneities. Experimental measurements were acquired using an imaging system consisting of a parallel plate-imaging chamber and a lens coupled charge coupled device camera, which enables conventional planar imaging as well as fluorescence tomography. To simulate increasing levels of background heterogeneity, we employed phantoms made of a fluorescent tube surrounded by several absorbers in different combinations of absorption distribution. We also investigated the effect of low absorbing thin layers (such as membranes). We show that the normalized Born approach accurately retrieves the position and shape of the fluorochrome even at high background heterogeneity. We also demonstrate that the quantification is relatively insensitive to a varying degree of heterogeneity and background optical properties. Findings are further contrasted to images obtained with the standard Born expansion and with a normalized approach that divides the fluorescent field with excitation measurements through a homogeneous medium. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Fdn Res & Technol Hellas, Inst Elect Struct & Laser, GR-71110 Iraklion, Greece. RP Soubret, A (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. EM asoubret@hms.harvard.edu; jripoll@iesl.forth.gr; vasilis@helix.ingh.harvard.edu RI Ripoll, Jorge/J-8134-2012 OI Ripoll, Jorge/0000-0001-8856-7738 FU NCI NIH HHS [R33 CA91807]; NIBIB NIH HHS [R01 EB 000750-2] NR 39 TC 174 Z9 175 U1 1 U2 8 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0278-0062 J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD OCT PY 2005 VL 24 IS 10 BP 1377 EP 1386 DI 10.1109/TMI.2005.857213 PG 10 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA 969LX UT WOS:000232236800013 PM 16229423 ER PT J AU Nicholson, MJ Hahn, M Wucherpfennig, KW AF Nicholson, MJ Hahn, M Wucherpfennig, KW TI Unusual features of self-peptide/MHC binding by autoimmune T cell receptors SO IMMUNITY LA English DT Review ID MYELIN BASIC-PROTEIN; MHC CLASS-II; THYMIC EPITHELIAL-CELLS; MULTIPLE-SCLEROSIS; STRUCTURAL BASIS; AFFINITY MATURATION; CRYSTAL-STRUCTURE; TRANSGENIC MICE; AMINO-ACIDS; RECOGNITION AB Structural studies on T cell receptors (TCRs) specific for foreign antigens demonstrated a remarkably similar topology characterized by a central, diagonal TCR binding mode that maximizes interactions with the MHC bound peptide. However, three recent structures involving autoimmune TCRs demonstrated unusual interactions with self-peptide/MHC complexes. Two TCRs from multiple sclerosis patients bind with unconventional topologies, and both TCRs are shifted toward the peptide N terminus and the MHC class II beta chain helix. A TCR from the experimental autoimmune encephalomyelitis (EAE) model binds in a conventional orientation, but the structure is unusual because the self-peptide only partially fills the binding site. For all three TCRs, interaction with the MHC bound self-peptide is suboptimal, and only two or three TCR loops contact the peptide. Optimal TCR binding modes confer a competitive advantage for antimicrobial T cells during an infection, whereas altered binding properties may permit survival of a subset of autoreactive T cells during thymic selection. C1 Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Program Immunol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. RP Wucherpfennig, KW (reprint author), Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Dana Farber Canc Inst, Boston, MA 02115 USA. EM kai_wucherpfennig@dfci.harvard.edu FU NIAID NIH HHS [R01 AI064177, P01 AI045757, P01 AI45757] NR 61 TC 32 Z9 32 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD OCT PY 2005 VL 23 IS 4 BP 351 EP 360 DI 10.1016/j.immuni.2005.09.009 PG 10 WC Immunology SC Immunology GA 980EC UT WOS:000232995800004 PM 16226501 ER PT J AU Cariappa, A Mazo, IB Chase, C Shi, HN Liu, HY Li, Q Rose, H Leung, H Cherayil, BJ Russell, P von Andrian, U Pillai, S AF Cariappa, A Mazo, IB Chase, C Shi, HN Liu, HY Li, Q Rose, H Leung, H Cherayil, BJ Russell, P von Andrian, U Pillai, S TI Perisinusoidal B cells in the bone marrow participate in T-independent responses to blood-borne microbes SO IMMUNITY LA English DT Article ID MARGINAL ZONE; GERMINAL-CENTERS; HEMATOPOIETIC STEM; B1B CELLS; MICE; ANTIGEN; EXPRESSION; ANTIBODY; MEMORY; SUBSETS AB Mature recirculating B cells are generally assumed to exist in follicular niches in secondary lymphoid organs, and these cells mediate T-dependent humoral immune responses. We show here that a large proportion of mature B lymphocytes occupy an anatomically and functionally distinct perisinusoidal niche in the bone marrow. Perisinusoidal B cells circulate freely, as revealed by parablosis studies. However, unlike their counterparts in the follicular niche, these cells are capable of being activated in situ by blood-borne microbes in a T-independent manner to generate specific IgM antibodies. The bone marrow represents a unique type of secondary lymphoid organ in which mature B cells are strategically positioned in the path of circulating microbes. C1 Massachusetts Gen Hosp, Boston, MA 02129 USA. Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02129 USA. RP Pillai, S (reprint author), Massachusetts Gen Hosp, Boston, MA 02129 USA. EM pillai@helix.mgh.harvard.edu RI von Andrian, Ulrich/A-5775-2008 FU NCI NIH HHS [CA102793]; NHLBI NIH HHS [HL071932, HL43340]; NIAID NIH HHS [AI54917] NR 54 TC 73 Z9 74 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD OCT PY 2005 VL 23 IS 4 BP 397 EP 407 DI 10.1016/j.immuni.2005.09.004 PG 11 WC Immunology SC Immunology GA 980EC UT WOS:000232995800008 PM 16226505 ER PT J AU DePaolo, RW Lathan, R Rollins, BJ Karpus, WJ AF DePaolo, RW Lathan, R Rollins, BJ Karpus, WJ TI The chemokine CCL2 is required for control of murine gastric Salmonella enterica infection SO INFECTION AND IMMUNITY LA English DT Article ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; NECROSIS-FACTOR-ALPHA; MACROPHAGE INFLAMMATORY PROTEIN-1-ALPHA; INTERLEUKIN-12 MESSENGER-RNA; T-CELL PROLIFERATION; DOSE ORAL TOLERANCE; NF-KAPPA-B; CYTOKINE PRODUCTION; ESCHERICHIA-COLI; EPITHELIAL-CELLS AB Salmonella enterica is a gram-negative intracellular pathogen that can cause a variety of diseases ranging from gastroenteritis to typhoid fever. The Typhimurium serotype causes gastroenteritis in humans; however, infection of mice results in an enteric fever that resembles human typhoid fever and has been used as a model for typhoid fever. The present study examined the role of the chemokine CCL2 in the control of Salmonella infection. Upon infection with salmonellae, mucosal expression of CCL2 is rapidly up-regulated, followed by systemic expression in the spleen. CCL2(-/-) mice became moribund earlier and had a higher rate of mortality compared to wild-type C57BL/6 mice. Moreover, CCL2(-/-) mice had significantly higher levels of bacteria in the liver compared to wild-type controls. Mucosal and serum interleukin-6 and tumor necrosis factor alpha levels were elevated in CCL2(-/-) mice compared to wild-type mice. In vitro analysis demonstrated that CCL2(-/-) macrophages infected with salmonellae resulted in dysregulated cytokine production compared to macrophages derived from wild-type mice. These data are the first to directly demonstrate CCL2 as a critical factor for immune responses and survival following S. enterica infection. C1 Northwestern Univ, Feinberg Sch Med, Dept Pathol, Chicago, IL 60611 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Karpus, WJ (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Pathol, 303 E Chicago Ave,W127, Chicago, IL 60611 USA. EM w-karpus@northwestern.edu OI DePaolo, William/0000-0002-3880-4544 FU NIAID NIH HHS [R01 AI035934] NR 69 TC 12 Z9 13 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD OCT PY 2005 VL 73 IS 10 BP 6514 EP 6522 DI 10.1128/IAI.73.10.6514-6522.2005 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 967JN UT WOS:000232087600035 PM 16177325 ER PT J AU Qadri, F Svennerholm, AM Shamsuzzaman, S Bhuiyan, TR Harris, JB Ghosh, AN Nair, GB Weintraub, A Faruque, SM Ryan, ET Sack, DA Calderwood, SB AF Qadri, F Svennerholm, AM Shamsuzzaman, S Bhuiyan, TR Harris, JB Ghosh, AN Nair, GB Weintraub, A Faruque, SM Ryan, ET Sack, DA Calderwood, SB TI Reduction in capsular content and enhanced bacterial susceptibility to serum killing of Vibrio cholerae O139 associated with the 2002 cholera epidemic in Bangladesh SO INFECTION AND IMMUNITY LA English DT Article ID NORTH-AMERICAN VOLUNTEERS; VIBRIO-CHOLERAE-O139 BENGAL; ANTIBODY-RESPONSES; IMMUNE-RESPONSES; WHOLE-CELL; O-ANTIGEN; VACCINE; POLYSACCHARIDE; SEROGROUP; INFECTION AB Vibrio cholerae O139 emerged in 1992 as a major cause of epidemic cholera. However, the incidence of disease due to this new serogroup subsequently decreased for almost a decade. In April 2002, there was a dramatic resurgence of V. cholerae O139 in Bangladesh. We compared the phenotypic properties of the bacterial isolates and the immunological responses in patients with disease due to V. cholerae O139 during the 2002 epidemic with those dating to the emergence of this disease in 1993 to 1995. Strains isolated from patients in the two time periods were compared with respect to capsular polysaccharide, their resistance to the bactericidal effect of serum, and their capacity to be used as target strains in complement-mediated vibriocidal assays. Phase-contrast microscopy showed that strains isolated in 2002 had less capsular material than those isolated from 1993 to 1995 (P = <0.001), a finding confirmed by electron microscopic studies. Strains isolated in 2002 were more susceptible to the bactericidal activity of serum compared to strains from 1993 to 1995 (P = 0.013). Compared to results using a standard O139 strain, a modified vibriocidal assay utilizing a 2002 strain, CIRS 134, as the target organism detected higher vibriocidal responses in both O139-infected cholera patients as well as O139 vaccine recipients. The vibriocidal assay utilizing the less encapsulated 2002 strain, CIRS 134, is a more sensitive indicator of adaptive immune responses to recent infection with V. cholerae O139. Consequently, this assay may be useful in studies of both O139-infected patients and recipients of O139 vaccines. C1 Int Ctr Diarrhoeal Dis Res, Div Sci Lab, Dhaka 1000, Bangladesh. Univ Gothenburg, Dept Med Microbiol & Immunol, S-40530 Gothenburg, Sweden. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Natl Inst Cholera & Enter Dis, Kolkata, India. Huddinge Univ Hosp, Dept Lab Med, Div Clin Bacteriol, Stockholm, Sweden. RP Qadri, F (reprint author), Int Ctr Diarrhoeal Dis Res, Div Sci Lab, B,GPO Box 128, Dhaka 1000, Bangladesh. EM fqadri@icddrb.org OI Weintraub, Andrej/0000-0003-3646-247X FU NIAID NIH HHS [U01 AI58935, U01 AI058935]; NICHD NIH HHS [K12 HD000850, K12-HD00850] NR 38 TC 13 Z9 13 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 EI 1098-5522 J9 INFECT IMMUN JI Infect. Immun. PD OCT PY 2005 VL 73 IS 10 BP 6577 EP 6583 DI 10.1128/IAI.73.10.6577-6583.2005 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 967JN UT WOS:000232087600043 PM 16177333 ER PT J AU Alam, A LaRocque, RC Harris, JB Vanderspurt, C Ryan, ET Qadri, F Calderwood, SB AF Alam, A LaRocque, RC Harris, JB Vanderspurt, C Ryan, ET Qadri, F Calderwood, SB TI Hyperinfectivity of human-passaged Vibrio cholerae can be modeled by growth in the infant mouse SO INFECTION AND IMMUNITY LA English DT Article ID ACID TOLERANCE; TOXR REGULON; PILUS GENE; EL-TOR; INFECTION; COLONIZATION; IDENTIFICATION; CHEMOTAXIS; ADAPTATION; DYNAMICS AB It has previously been shown that passage of Vibrio cholerae through the human intestine imparts a transient hyperinfectious phenotype that may contribute to the epidemic spread of cholera. The mechanism underlying this human-passaged hyperinfectivity is incompletely understood, in part due to inherent difficulties in recovering and studying organisms that are freshly passed in human stool. Here, we demonstrate that passage of V cholerae through the infant mouse intestine leads to an equivalent degree of hyperinfectivity as passage through the human host. We have used this infant mouse model of host-passaged hyperinfectivity to characterize the timing and the anatomic location of the competitive advantage of mouse-passaged V cholerae as well as the contribution of three type IV pili to the phenotype. C1 Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Int Ctr Diarrhoeal Dis Res, Dhaka 1000, Bangladesh. Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. RP LaRocque, RC (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Gray Jackson 504,55 Fruit St, Boston, MA 02114 USA. EM rclarocque@partners.org FU FIC NIH HHS [D43-TW05572, D43 TW005572, K01 TW007144, K01-TW07144]; NIAID NIH HHS [AI40725, R01 AI040725, T32 AI007061, U01 AI058935, U01-AI58935]; NICHD NIH HHS [K12 HD000850, K12-HD00850] NR 28 TC 37 Z9 42 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD OCT PY 2005 VL 73 IS 10 BP 6674 EP 6679 DI 10.1128/IAI.73.10.6674-6679.2005 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 967JN UT WOS:000232087600054 PM 16177344 ER PT J AU Wu, HM Fornek, M Schwab, KJ Chapin, AR Gibson, K Schwab, E Spencer, C Henning, K AF Wu, HM Fornek, M Schwab, KJ Chapin, AR Gibson, K Schwab, E Spencer, C Henning, K TI A norovirus outbreak at a long-term-care facility: The role of environmental surface contamination SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article; Proceedings Paper CT 2nd World Calicivirus Conference CY NOV 06-10, 2004 CL Dijon, FRANCE ID NORWALK-LIKE VIRUSES; ROUND-STRUCTURED VIRUSES; VIRAL GASTROENTERITIS; UNITED-STATES; HOSPITAL OUTBREAK; HOTEL OUTBREAK; NURSING-HOME; NLV; TRANSMISSION; INFECTION AB BACKGROUND: The role of environmental surface contamination in the propagation of norovirus outbreaks is unclear. An outbreak of acute gastroenteritis was reported among residents of a 240-bed veterans long-term-care facility. OBJECTIVES: To identify the likely mode of transmission, to characterize risk factors for illness, and to evaluate for environmental contamination in this norovirus outbreak. METHODS: An outbreak investigation was conducted to identify risk factors for illness among residents and employees. Stool and vomitus samples were tested for norovirus by reverse transcription polymerase chain reaction (RT-PCR). Fourteen days after outbreak detection, ongoing cases among the residents prompted environmental surface testing for norovirus by RT-PCR. RESULTS: One hundred twenty-seven (52%) of 246 residents and 84 (46%) of 181 surveyed employees had gastroenteritis. Case-residents did not differ from non-case-residents by comorbidities, diet, room type, or level of mobility. Index cases were among the nursing staff. Eight of 11 resident stool or vomitus samples tested positive for genogroup II norovirus. The all-cause mortality rate during the month of the outbreak peak was significantly higher than the expected rate. Environmental surface swabs from case-resident rooms, a dining room table, and an elevator button used only by employees were positive for norovirus. Environmental and clinical norovirus sequences were identical. CONCLUSION: Extensive contamination of environmental surfaces may play a role in prolonged norovirus outbreaks and should be addressed in control interventions. C1 Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. RP Wu, HM (reprint author), Drexel Univ, Coll Med, Mailstop 461,245 N 15th St, Philadelphia, PA 19102 USA. EM hwu@drexelmed.edu RI Sapkota, Amy/A-6046-2011 NR 40 TC 118 Z9 123 U1 2 U2 20 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0899-823X J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD OCT PY 2005 VL 26 IS 10 BP 802 EP 810 DI 10.1086/502497 PG 9 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 975TE UT WOS:000232684000003 PM 16276954 ER PT J AU Lorenz, K Ryan, G Morton, SC Chan, KS Wang, S Shekelle, PG AF Lorenz, K Ryan, G Morton, SC Chan, KS Wang, S Shekelle, PG TI A qualitative examination of primary care providers' and physician managers' uses and views of research evidence SO INTERNATIONAL JOURNAL FOR QUALITY IN HEALTH CARE LA English DT Article DE evidence-based medicine; focus groups ID EVIDENCE-BASED MEDICINE; GENERAL-PRACTITIONERS; ATRIAL-FIBRILLATION; AUSTRALIAN GPS; UNITED-STATES; OF-CARE AB Objectives. To examine the reasons and search strategies related to physicians' search for evidence and to compare clinician and physician manager approaches. Design. Qualitative analysis of verbatim transcripts of four focus groups in 2002. Study setting. Clinicians and managers in community practices in Southern California. Participants. Pediatricians, family practitioners, and general internists (i.e. child and adult primary care providers) in nonacademic practice and physician managers whose primary responsibility involved making management decisions within a moderate to large sized health care delivery system (e.g. health plan, community hospital, large group practice). Main outcome measures. Themes related to clinician and manager reasons for using evidence and approach to selecting among evidence sources. Results. Clinicians and managers differed substantially in their reasons for using evidence. Whereas clinicians consistently invoked clinical intuition as a guide to most routine clinical decisions, managers articulated both motivation and interest in using medical research to guide decision-making, most commonly prompted by cost. Both clinicians and managers rated trustworthiness as a paramount consideration in arbitrating between evidence sources, because neither group evinced comfort with the complexity of primary literature. Both groups expressed a preference for tested, convenient, and respected evidence sources such as expert colleagues and professional societies. Conclusions. Because clinicians invoke intuition in confronting the challenges of daily practice, evidence-based medicine interventions that target managers are likely to have larger effects on health outcomes than those that target primary care providers and individual patient treatment. Ensuring trustworthiness of evidence is of the utmost importance. Because both groups express discomfort with the format of primary evidence sources, strategies should probably not rely on individual appraisal. C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RAND Corp, Santa Monica, CA USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. RP Lorenz, K (reprint author), Vet Integrated Palliat Program, 11301 Wishire Blvd,Code 111-G, Los Angeles, CA 90064 USA. EM karl.lorenz@med.va.gov NR 29 TC 17 Z9 17 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1353-4505 J9 INT J QUAL HEALTH C JI Int. J. Qual. Health Care PD OCT PY 2005 VL 17 IS 5 BP 409 EP 414 DI 10.1093/intqhc/mzi054 PG 6 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 974GO UT WOS:000232579500006 PM 15923281 ER PT J AU Schulze, PC Spate, U AF Schulze, PC Spate, U TI Insulin-like growth factor-1 and muscle wasting in chronic heart failure SO INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY LA English DT Review DE IGF-1; cytokines; growth factors; hormones; skeletal muscle ID TUMOR-NECROSIS-FACTOR; NITRIC-OXIDE SYNTHASE; RAT SKELETAL-MUSCLE; KAPPA-B ACTIVATION; FOXO TRANSCRIPTION FACTORS; FIBER-TYPE DISTRIBUTION; CAMP-RESPONSE ELEMENT; FACTOR-ALPHA; GENE-EXPRESSION; TRANSGENIC MICE AB Chronic heart failure is a clinical syndrome of cardiac origin, which affects varies organ systems. It is associated with metabolic abnormalities leading to a catabolic syndrome in advanced stages of the disease. As in several other chronic diseases, skeletal muscle dysfunction and structural muscle abnormalities result in progressive muscle wasting and cachexia. These changes are accompanied by increased expression of proinflammatory cytokines, increased rate of apoptosis and activation of the proteolytic ubiquitin-proteasome pathway. Further, reduced expression of the local anabolic insulin-like growth factor-1 has been demonstrated in skeletal muscle of animals and patients with chronic heart failure. This suppression occurs in the presence of normal serum levels of insulin-like growth factor-1. In addition to catabolic effects of proinflammatory cytokines, these recent findings are consistent with reduced anabolism involving altered local insulin-like growth factor-1 levels in progressive muscle atrophy in chronic heart failure. This article describes local effects of insulin-like growth factor-1 on skeletal muscle function and morphology, its role in stem cell recruitment and muscle regeneration as well as its regulation in circumstances of muscle inflammation and wasting. (c) 2005 Elsevier Ltd. All rights reserved. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Cardiovasc Div,Dept Med, Boston, MA 02115 USA. Forsyth Inst, Dept Cytokine Biol, Boston, MA USA. RP Schulze, PC (reprint author), Partners Res Facil, Cardiovasc Res, 65 Landsdowne St Room 283, Cambridge, MA 02139 USA. EM pcschulze@rics.bwh.harvard.edu NR 98 TC 25 Z9 28 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1357-2725 J9 INT J BIOCHEM CELL B JI Int. J. Biochem. Cell Biol. PD OCT PY 2005 VL 37 IS 10 BP 2023 EP 2035 DI 10.1016/j.biocel.2005.04.017 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 967JS UT WOS:000232088100011 PM 15964237 ER PT J AU D'Arceuil, HE de Crespigny, AJ Pelc, L Howard, D Seri, S Hashiguchi, Y Nakatani, A Moseley, ME AF D'Arceuil, HE de Crespigny, AJ Pelc, L Howard, D Seri, S Hashiguchi, Y Nakatani, A Moseley, ME TI A comparison of CH3-DTPA-GD (NMS60) and GD-DTPA for evaluation of acute myocardial ischemia SO INTERNATIONAL JOURNAL OF CARDIOVASCULAR IMAGING LA English DT Article DE CE-MRA; contrast agents; gadolinium; magnetic resonance imaging; myocardial perfusion; pigs ID CONTRAST-ENHANCED MRI; CORONARY-ARTERY OCCLUSION; INFARCTED MYOCARDIUM; DELAYED-ENHANCEMENT; IMAGING TIME; CANINE MODEL; VIABILITY; AGENT; THROMBOSIS; PIGS AB Purpose: Our objective was to evaluate the use of a new medium weight MRI contrast agent, NMS60 (a synthetic oligomeric Gd-complex containing three Gd(3+)atoms, molecular weight 2158 Da) compared to gadolinium-diethylene triamine pentaacetic acid (Gd-DTPA) in a pig myocardial ischemia model. Materials: We used 13 male white hybrid pigs. Animals were scanned in the acute phase 2-3 h after the onset of myocardial ischemia. Scans were acquired on a 1.5T GE Signa with dynamic T1-weighted imaging during a bolus injection of 0.1 mmol(gd)/kg of either NMS60 or Gd-DTPA, 2D CINE at 5 min after injection, and T1-weighted spin-echo imaging up to 60 min. Results: The postcontrast CINE scans showed improved contrast-to-noise ratio after NMS60 injection, compared to Gd-DTPA. There was significantly greater enhancement with NMS60 in both normal myocardium and in the ischemic lesion on T1-weighted spin-echo scans up to 60 min after injection. The dose ranging study shows a 24% greater enhancement with NMS60 compared to Gd-DTPA. Discussion: This new medium weighted contrast agent offers improved enhancement for cardiac MRI, compared to Gd-DTPA, with similar washout kinetics and lower toxicity, and may prove useful for better detection of myocardial ischemia as well as delayed or hyperenhancement after reperfusion. C1 Stanford Univ, Dept Radiol, Lucas MRS I Ctr, Stanford, CA 94305 USA. Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA USA. Nihon Medi Phys Co Ltd, Clin Dev Dept, Tokyo, Japan. Nihon Medi Phys Co Ltd, Res Ctr, Chiba, Japan. RP D'Arceuil, HE (reprint author), Lucas MRS I Ctr, Dept Radiol, Rm 2301,Bldg 149,13th St, Charlestown, MA 02129 USA. EM helen@nmr.mgh.harvard.edu FU NCRR NIH HHS [RR-09784]; NINDS NIH HHS [1R01NS35959] NR 33 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1569-5794 J9 INT J CARDIOVAS IMAG JI Int. J. Cardiovasc. Imaging PD OCT PY 2005 VL 21 IS 5 BP 539 EP 547 DI 10.1007/s10554-005-2103-4 PG 9 WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine & Medical Imaging GA 966OR UT WOS:000232030800012 PM 16175444 ER PT J AU Campo-Ruiz, V Patel, D Anderson, RR Delgado-Baeza, E Gonzalez, S AF Campo-Ruiz, V Patel, D Anderson, RR Delgado-Baeza, E Gonzalez, S TI Evaluation of human knee meniscus biopsies with near-infrared, reflectance confocal microscopy. A pilot study SO INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY LA English DT Article DE cartilage; human meniscus; knee; laser confocal microscopy ID SCANNING LASER MICROSCOPY; IN-VIVO; HUMAN SKIN; HISTOLOGY; JOINT AB Knee cartilage biopsy is used to confirm the pathology in both clinical and experimental conditions and often guides diagnosis and therapeutic strategies. Current histopathological techniques are time consuming, induce tissue artefacts and often prevent further evaluation, once the tissue has been fixed. Hence, there is a potential need for a fast and nondestructive imaging technique for unfixed tissue. Near-infrared, reflectance confocal microscopy (CM) allows real-time, virtual sectioning of unstained, bulk tissue samples. This pilot study evaluates the use of CM in the assessment of meniscus histopathology in a series of 26 freshly-excised human meniscus samples compared to standard light microscopy of stained sections. CM images of the meniscus show cell and matrix detail, depicting morphologic features of collagen and elastic fibres, vessels and nerve endings. In addition, crystal deposits of gout and pseudogout are also demonstrable. Thus, CM is a novel imaging technique that could enable the pathologist to make a rapid microscopic evaluation of cartilage in a fresh and unfixed fashion. C1 Harvard Univ, Massachusetts Gen Hosp, Wellman Labs Photomed, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. Univ Autonoma Madrid, Sch Med, Dept Morphol Histol, Orthopaed Res Unit, Madrid, Spain. RP Gonzalez, S (reprint author), Harvard Univ, Massachusetts Gen Hosp, Wellman Labs Photomed, BHX 630,55 Fruit St, Boston, MA 02114 USA. EM sgonzalez3@partners.org NR 24 TC 5 Z9 5 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0959-9673 J9 INT J EXP PATHOL JI Int. J. Exp. Pathol. PD OCT PY 2005 VL 86 IS 5 BP 297 EP 307 DI 10.1111/j.0959-9673.2005.00439.x PG 11 WC Pathology SC Pathology GA 968DM UT WOS:000232142100004 PM 16191102 ER PT J AU Gans, JS AF Gans, JS TI A plea for greater recognition and appreciation of our group members' courage SO INTERNATIONAL JOURNAL OF GROUP PSYCHOTHERAPY LA English DT Article ID GROUP-THERAPY; RESISTANCE; ISSUES; SELF AB Courage-a mental act that involves a decision to face and deal with emotional pain as honestly as possible without an guarantee of a positive outcome-resides at the heart of the therapeutic alliance and the work of psychodynamic group therapy. The author's experience suggests that group therapists tend to take for granted or underestimate the courage required to join and participate in a psychodynamic therapy group. Written from the Perspective of self-psychology, this article provides a theoretical rationale for courage recognition as a central and crucial leadership function. Examples of courage are presented and contrasted with behaviors that appear courageous but are not. A detailed case example discusses the courage it takes for dyads to work through reciprocal negative transferences. Suggestions are offered to assist the group therapist in recognizing and calling attention to courageous behaviors. The author discusses some of the pitfalls of our profession's preference for value-free language and then shows how and why the occasional and judicious use of non-neutral language, courage being an example, can facilitate and deepen group work. C1 Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Gans, JS (reprint author), 55 Cleveland Rd, Wellesley, MA 02481 USA. EM Jsgans@comcast.net NR 28 TC 7 Z9 7 U1 1 U2 1 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0020-7284 J9 INT J GROUP PSYCHOTH JI Int. J. Group Psychother. PD OCT PY 2005 VL 55 IS 4 BP 575 EP 593 DI 10.1521/ijgp.2005.55.4.575 PG 19 WC Psychology, Clinical SC Psychology GA 969MH UT WOS:000232237800005 PM 16232114 ER PT J AU Parker, RL Young, RH Clement, PB AF Parker, Robin L. Young, Robert H. Clement, Philip B. TI Skeletal muscle-like and rhabdoid cells in uterine leiomyomas SO INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY LA English DT Article DE leiomyomas; skeletal muscle; rhabdoid cells. ID ENDOMETRIAL STROMAL SARCOMA; CORD-LIKE AREAS; FETAL RHABDOMYOMA; UTERUS; DIFFERENTIATION; TUMOR; LEIOMYOSARCOMA; FEATURES; CORPUS AB We describe eight unusual uterine leiomyomas characterized by a component of cells that suggested skeletal muscle differentiation or resembled the rhabdoid cells of extrarenal rhabdoid tumors. All of the tumors were referred because of problems in differential diagnosis, particularly distinction from an epithelioid smooth muscle tumor, a smooth muscle tumor of uncertain malignant potential, or a tumor with skeletal muscle differentiation. The patients were aged 27 to 50 (mean, 38) years, and the presenting clinical features and gross appearance of the tumors were similar to those of typical uterine leiomyomas. On microscopic examination, seven of the tumors were well circumscribed, whereas one showed slight irregularity of its margin. The characteristic feature of the tumors was a variable number of rounded, polygonal, or strap-shaped cells with abundant deeply eosinophilic cytoplasm and fibrillar, or occasionally hyaline, intracytoplasmic globules. Cytoplasmic cross-striations were not identified. The cells usually had eccentric, round-to-oval nuclei with conspicuous nucleoli. A variable number of the rhabdoid/skeletal muscle-like cells, as well as cells without these features, contained multiple or multilobed, pleomorphic, hyperchromatic nuclei, thus qualifying the tumors as leiomyomas with bizarre nuclei. Foci of hydropic change were present in all of the tumors. The mitotic index was low (< 1 mitotic figure/10 high-power fields) and necrosis was absent in all the tumors. The rhabdoid/skeletal muscle-like cells were immunoreactive for desmin and h-caldesmon, but not for cytokeratin (AE1/AE3) or skeletal muscle markers (myoglobin, Myo-D1, or myogenin). Intracytoplasmic whorls of intermediate filaments were observed in the cells of one case examined by electron microscopy; there was no ultrastructural evidence of skeletal muscle differentiation. The histologic, immunohistochemical, and ultrastructural features indicated that the peculiar cells in these leiomyomas likely represented smooth muscle cells with an unusual phenotype rather than the cells of uterine tumors with skeletal muscle differentiation, extrarenal rhabdoid tumors, or epithelioid smooth muscle tumors. An association with leiomyomas with bizarre nuclei also was suggested. C1 Univ Calgary, Dept Pathol & Lab Med, Foothills Med Ctr, Calgary, AB T2N 2T9, Canada. Calgary Lab Serv, Dept Pathol & Lab Med, Calgary, AB, Canada. Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Vancouver Hosp & Hlth Sci Ctr, Dept Pathol, Vancouver, BC V5Z 1M9, Canada. Univ British Columbia, Dept Pathol, Vancouver, BC V5Z 1M9, Canada. RP Parker, RL (reprint author), Univ Calgary, Dept Pathol & Lab Med, Foothills Med Ctr, 1403-29th St,NW, Calgary, AB T2N 2T9, Canada. NR 27 TC 8 Z9 11 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-1691 J9 INT J GYNECOL PATHOL JI Int. J. Gynecol. Pathol. PD OCT PY 2005 VL 24 IS 4 BP 319 EP 325 DI 10.1097/01.pgp.0000177647.45890.b5 PG 7 WC Obstetrics & Gynecology; Pathology SC Obstetrics & Gynecology; Pathology GA 140NK UT WOS:000244512000003 PM 16175075 ER PT J AU Gifford, KA Horton, JL Pelloski, CE Jhingran, A Court, LE Mourtada, F Eifel, PJ AF Gifford, KA Horton, JL Pelloski, CE Jhingran, A Court, LE Mourtada, F Eifel, PJ TI A three-dimensional computed tomography-assisted Monte Carlo evaluation of ovoid shielding on the dose to the bladder and rectum in intracavitary radiotherapy for cervical cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE intracavitary therapy; brachytherapy; Monte Carlo; ovoids; Cs-137 ID DOSIMETRIC ANALYSIS; UTERINE CERVIX; BRACHYTHERAPY; CARCINOMA; IMPLANTS; SURFACE; APPLICATOR; COLPOSTATS; HISTOGRAMS; THERAPY AB Purpose: To determine the effects of Fletcher Suit Delclos ovoid shielding on dose to the bladder and rectum during intracavitary radiotherapy for cervical cancer. Methods and Materials: The Monte Carlo method was used to calculate the dose in 12 patients receiving low-dose-rate intracavitary radiotherapy with both shielded and unshielded ovoids. Cumulative dose-difference surface histograms were computed for the bladder and rectum. Doses to the 2-cm(3) and 5-cm(3) volumes of highest dose were computed for the bladder and rectum with and without shielding. Results: Shielding affected dose to the 2-cm(3) and 5-cm(3) volumes of highest dose for the rectum (10.1% and 11.1% differences, respectively). Shielding did not have a major impact on the dose to the 2-cm(3) and 5-cm(3) volumes of highest dose for the bladder. The average dose reduction to 5% of the surface area of the bladder was 53 cGy. Reductions as large as 150 cGy were observed to 5% of the surface area of the bladder. The average dose reduction to 5% of the surface area of the rectum was 195 cGy. Reductions as large as 405 cGy were observed to 5% of the surface area of the rectum. Conclusions: Our data suggest that the ovoid shields can greatly reduce the radiation dose delivered to the rectum. We did not find the same degree of effect on the dose to the bladder. To calculate the dose accurately, however, the ovoid shields must be included in the dose model. (c) 2005 Elsevier Inc. C1 Univ Texas, MD Anderson Canc Ctr, Dept Radiat Phys,Div Radiat Oncol, Unit 94, Houston, TX 77030 USA. Brigham & Womens Hosp, Dana Farber Canc Ctr, Dept Radiat Oncol, Boston, MA USA. RP Gifford, KA (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Radiat Phys,Div Radiat Oncol, Unit 94, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM kagifford@mail.mdanderson.org NR 24 TC 12 Z9 12 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD OCT 1 PY 2005 VL 63 IS 2 BP 615 EP 621 DI 10.1016/j.ijrobp.2005.03.043 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 967IA UT WOS:000232083700037 PM 16168853 ER PT J AU Hu, M Kearney, P Badger, J AF Hu, M Kearney, P Badger, J TI A collapsing method for the efficient recovery of optimal edges in phylogenetic trees SO INTERNATIONAL JOURNAL ON ARTIFICIAL INTELLIGENCE TOOLS LA English DT Article ID MAXIMUM-LIKELIHOOD; TOPOLOGIES; SIMULATION; SEQUENCES AB As the amount of sequencing efforts and genomic data volume continue to increase at an accelerated rate, phylogenetic analysis provides an evolutionary context for understanding and interpreting this growing set of complex data. We introduce a novel quartet based method for inferring molecular based phylogeny called hypercleaning* (HC*). The HC* method is based on the hypercleaning (HC) technique,(2) which possesses an interesting property of recovering edges (of a phylogenetic tree) that are best supported by the witness quartet set. HC* extends HC in two regards: (i) whereas HC constrains the input quartet set to be unweighted (binary valued), HC* allows any positive valued quartet scores, enabling more informative quartets to be defined. (ii) HC* employs a novel collapsing technique which significantly speeds up the inference stage, making it empirically on par with quartet puzzling in terms of speed, while still guaranteeing optimal edge recovery a:; in HC. This paper is primarily aimed at presenting the algorithmic construction of HC*. We also report some preliminary studies on an implementation of HC* as a potentially powerful approximation scheme for maximum likelihood based inference. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Caprion Pharmaceut, Montreal, PQ H4S 2C8, Canada. Inst Gen Res, Rockville, MD 20850 USA. RP Hu, M (reprint author), Dana Farber Canc Inst, 44 Binney St,Sm1058, Boston, MA 02115 USA. EM mike_hu@dfci.harvard.edu; pkearney@caprion.com; jbadger@tigr.org NR 17 TC 0 Z9 0 U1 0 U2 0 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA 5 TOH TUCK LINK, SINGAPORE 596224, SINGAPORE SN 0218-2130 J9 INT J ARTIF INTELL T JI Int. J. Artif. Intell. Tools PD OCT PY 2005 VL 14 IS 5 BP 717 EP 731 DI 10.1142/S0218213005002351 PG 15 WC Computer Science, Artificial Intelligence; Computer Science, Interdisciplinary Applications SC Computer Science GA 986SI UT WOS:000233469600003 ER PT J AU Strom, C Sander, B Klemp, K Aiello, LP Lund-Andersen, H Larsen, M AF Strom, C Sander, B Klemp, K Aiello, LP Lund-Andersen, H Larsen, M TI Effect of ruboxistaurin on blood-retinal barrier permeability in relation to severity of leakage in diabetic macular edema SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID PKC-BETA; RETINOPATHY; FLUOROMETRY; COMPLICATIONS; FLUORESCEIN; INHIBITOR; MELLITUS AB PURPOSE. The purpose of the study was to investigate the effect of orally administered ruboxistaurin (RBX, LY333531), a selective protein kinase C beta inhibitor, on the permeability of the blood-retinal barrier in patients with diabetic macular edema. METHODS. Forty-one patients with diabetic macular edema were randomly assigned to an 18-month randomized, placebo-controlled, double-masked trial including four study arms (4, 16, or 32 mg/d RBX, or placebo). The RBX group comprised 30 patients ( 42 eyes) and the placebo group 11 patients (13 eyes). Retinal vascular leakage was assessed using vitreous fluorometry at baseline and after 3, 12, and 18 months. Statistical analysis of the effect of treatment accounted for repeated measurements and tested potential interaction with baseline permeability, HbA(1c), and arterial blood pressure. RESULTS. Statistical analysis and modeling demonstrated a significant interaction between RBX treatment at any dosage and baseline permeability (P = 0.032, mixed models). A threefold or higher increase in retinal vascular leakage at baseline was associated with a significant reduction (30%) in retinal vascular leakage after RBX treatment compared with placebo. Visual acuity was normal at baseline and remained unchanged throughout the study. CONCLUSIONS. RBX treatment was associated with a reduction of retinal vascular leakage in eyes that had diabetic macular edema and markedly elevated leakage at baseline. These data suggest that clinical benefit from RBX treatment may be most prominent in patients with severe macular edema at baseline, and trials investigating this therapy may benefit from stratification according to baseline leakage. C1 Univ Copenhagen, Herlev Hosp, Dept Ophthalmol, DK-2730 Herlev, Denmark. Harvard Univ, Sch Med, Boston, MA USA. Joslin Diabet Ctr, Beetham Eye Inst, Boston, MA 02215 USA. RP Larsen, M (reprint author), Univ Copenhagen, Herlev Hosp, Dept Ophthalmol, Herlev Ringvej 75, DK-2730 Herlev, Denmark. EM mla@dadlnet.dk RI Lund-Andersen, Henrik/C-1003-2012; Larsen, Michael/E-9620-2010 OI Larsen, Michael/0000-0002-5172-5891 NR 20 TC 38 Z9 38 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD OCT PY 2005 VL 46 IS 10 BP 3855 EP 3858 DI 10.1167/iovs.05-0096 PG 4 WC Ophthalmology SC Ophthalmology GA 967TA UT WOS:000232112900055 PM 16186374 ER PT J AU Greenberg, JA Newmann, SJ Howell, AB AF Greenberg, JA Newmann, SJ Howell, AB TI Consumption of sweetened dried cranberries versus unsweetened raisins for inhibition of uropathogenic Escherichia coli adhesion in human urine: A pilot study SO JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE LA English DT Article ID TRACT INFECTIONS; JUICE; ADHERENCE; PROANTHOCYANIDINS AB Objectives: The aim of this study was to determine whether consumption of sweetened dried cranberries elicits urinary anti-adherence properties against Escherichia coli as previously demonstrated with cranberry juice and/or sweetened cranberry juice cocktail, compared to unsweetened raisins. Design: Uropathogenic E. coli isolates were obtained from five women with culture-confirmed urinary tract infections (UTIs). Four urine samples were collected from each subject. The first urine sample was collected before any study intervention. The second urine sample was collected 2-5 hours after consumption of one box (42.5 g) of raisins. The third urine sample was collected 5-7 days later. The final urine sample was collected 2-5 hours after consumption of approximately 42.5 g of dried cranberries. Materials and methods: E. coli isolates were incubated separately in each of the four urine samples collected from the five subjects. Bacteria were harvested from the urine and tested for the ability to prevent adhesion of P-fimbriated E. coli bacteria using a mannose-resistant hemagglutination assay with human red blood cells (A(1), Rh+). Results: Of the urine samples collected after dried cranberry consumption, one demonstrated 50% antiadherence activity, two demonstrated 25% activity, and two did not show any increased activity. None of the control urine samples and none of the postraisin consumption samples demonstrated any inhibitory activity. Conclusions: Data from this pilot study on only five subjects suggest that consumption of a single serving of sweetened dried cranberries may elicit bacterial antiadhesion activity in human urine, whereas consumption of a single serving of raisins does not. Further studies are needed to verify the antiadhesion effect of sweetened dried cranberries. In addition, dose-response and pharmacokinetics of the active compounds in the dried cranberries need to be, determined. If clinical research is positive, dried cranberries could potentially be a viable alternative to cranberry juice consumption for prevention of UTIs. C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Rutgers State Univ, Marucci Ctr Blueberry Cranberry Res, Chatsworth, NJ USA. RP Greenberg, JA (reprint author), 1153 Ctr St,Suite 36, Boston, MA 02130 USA. EM jagreenberg@partners.org NR 12 TC 31 Z9 32 U1 0 U2 4 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1075-5535 J9 J ALTERN COMPLEM MED JI J. Altern. Complement Med. PD OCT PY 2005 VL 11 IS 5 BP 875 EP 878 DI 10.1089/acm.2005.11.875 PG 4 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 988QO UT WOS:000233615900027 PM 16296921 ER PT J AU Patel, SR AF Patel, SR TI Shared genetic risk factors for obstructive sleep apnea and obesity SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE susceptibility genes; pleiotropy; gene X. environment effects ID BODY-MASS INDEX; SERUM LEPTIN LEVELS; INTRAABDOMINAL VISCERAL FAT; QUANTITATIVE TRAIT LOCUS; RECEPTOR-GAMMA GENE; WHOLE-GENOME SCAN; UNCOUPLING PROTEINS; BETA-3-ADRENERGIC RECEPTOR; VENTILATORY-CONTROL; ELEVATED GHRELIN AB Both obesity and obstructive sleep apnea (OSA) are complex disorders with multiple risk factors, which interact in a complicated fashion to determine the overall phenotype. In addition to environmental risk factors, each disorder has a strong genetic basis that is likely due to the summation of small to moderate effects from a large number of genetic loci. Obesity is a strong risk factor for sleep apnea, and there are some data to suggest sleep apnea may influence obesity. It is therefore not surprising that many susceptibility genes for obesity and OSA should be shared. Current research suggests that approximately half of the genetic variance in the apnea hypopnea index is shared with obesity phenotypes. Genetic polymorphisms that increase weight will also be risk factors for apnea. In addition, given the interrelated pathways regulating both weight and other intermediate phenotypes for sleep apnea such as ventilatory control, upper airway muscle function, and sleep characteristics, it is likely that there are genes with pleiotropic effects independently impacting obesity and OSA traits. Other genetic loci likely interact with obesity to influence development of OSA in a gene-by-environment type of effect. Conversely, environmental stressors such as intermittent hypoxia and sleep fragmentation produced by OSA may interact with obesity susceptibility genes to modulate the-importance that these loci have on defining obesity-related traits. C1 Brigham & Womens Hosp, BWH Sleep Disorders Program, BIDMC, Div Sleep Med, Boston, MA 02115 USA. RP Patel, SR (reprint author), Brigham & Womens Hosp, BWH Sleep Disorders Program, BIDMC, Div Sleep Med, 75 Francis St, Boston, MA 02115 USA. EM spatel@partners.org OI Patel, Sanjay/0000-0002-9142-5172 NR 95 TC 36 Z9 41 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD OCT PY 2005 VL 99 IS 4 BP 1600 EP 1606 DI 10.1152/japplphysiol.00501.2005 PG 7 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 970AE UT WOS:000232276800050 PM 16160021 ER PT J AU Delinsky, SS AF Delinsky, SS TI Cosmetic surgery: A common and accepted form of self-improvement? SO JOURNAL OF APPLIED SOCIAL PSYCHOLOGY LA English DT Article ID BREAST AUGMENTATION SURGERY; BODY SHAPE QUESTIONNAIRE; SOCIOCULTURAL ATTITUDES; EATING DISORDERS; APPEARANCE; DISSATISFACTION; VALIDATION; INTERVIEW AB The pursuit of beauty through alteration of physical appearance is a growing trend. Rates of cosmetic surgery have soared, suggesting that surgery is a common, acceptable solution to the desire for self-improvement. Despite indications that surgeries are increasing in frequency, there have been few empirical investigations about popular attitudes toward cosmetic surgery. In the present study, 302 female undergraduate students were surveyed. Approximately 3% of the sample had undergone cosmetic surgery themselves, and half knew at least I person among their friends and family who had undergone cosmetic surgery. As hypothesized, approval and reported future likelihood of cosmetic surgery were predicted by greater media exposure, greater vicarious experience of cosmetic surgery, and greater importance of appearance to self-worth. No significant differences among ethnic groups were found. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Delinsky, SS (reprint author), Dept Psychiat, 15 Parkman St,WAC 812, Boston, MA 02114 USA. EM sdelinsky@partners.org NR 30 TC 41 Z9 43 U1 1 U2 12 PU V H WINSTON & SON INC PI PALM BEACH PA 360 SOUTH OCEAN BLVD, PH-B, PALM BEACH, FL 33480 USA SN 0021-9029 J9 J APPL SOC PSYCHOL JI J. Appl. Soc. Psychol. PD OCT PY 2005 VL 35 IS 10 BP 2012 EP 2028 DI 10.1111/j.1559-1816.2005.tb02207.x PG 17 WC Psychology, Social SC Psychology GA 002NL UT WOS:000234618100002 ER PT J AU Bozic, KJ Durbhakula, S Berry, DJ Naessens, JM Rappaport, K Cisternas, M Saleh, KJ Rubash, HE AF Bozic, KJ Durbhakula, S Berry, DJ Naessens, JM Rappaport, K Cisternas, M Saleh, KJ Rubash, HE TI Differences in patient and procedure characteristics and hospital resource use in primary and revision total joint arthroplasty - A multicenter study SO JOURNAL OF ARTHROPLASTY LA English DT Article; Proceedings Paper CT 15th Annual Meeting of the American-Association-of-Hip-and-Knee-Surgeons CY NOV 04-06, 2005 CL Dallas, TX SP Amer Assoc Hip & Knee Surg DE resource use; primary total joint arthroplasty; revision total joint arthroplasty; economic analysis ID TOTAL HIP-ARTHROPLASTY; LIVER-TRANSPLANTATION; COST-ANALYSIS; REGISTER; REIMBURSEMENT AB A multicenter retrospective cost-identification cohort study was undertaken to analyze clinical, demographic, and economic data for 4533 consecutive total hip arthroplasty (THA) and 3508 consecutive total knee arthroplasty (TKA) procedures performed during a 3-year period in 1 of 3 hospitals. Statistically significant differences were found between primary and revision procedures with respect to patient age, sex, payer type, mean total operative time, use of allograft, average length of hospital stay, discharge disposition, and hospital costs. significant differences were also found between different types of revision total joint arthroplasty (TJA) procedures. Our findings could be used to help improve the accuracy of administrative claims data related to primary and revision TJA procedures to identify relevant differences in patient characteristics, procedure characteristics, and hospital resource use. C1 Univ Calif San Francisco, Dept Orthopaed Surg, San Francisco, CA 94143 USA. Univ Calif San Francisco, Inst Hlth Policy Studies, San Francisco, CA 94143 USA. Orthopaed Specialty Ctr, Baltimore, MD USA. Mayo Clin, Dept Orthopaed Surg, Rochester, MN USA. Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA. MGC Data Serv, Carlsbad, CA USA. Univ Virginia, Dept Orthopaed Surg, Hlth Syst, Charlottesville, VA USA. Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. RP Bozic, KJ (reprint author), Univ Calif San Francisco, Dept Orthopaed Surg, 500 Parnassus,MU 320W, San Francisco, CA 94143 USA. OI Saleh, Khaled/0000-0002-7734-1933 NR 24 TC 42 Z9 43 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0883-5403 J9 J ARTHROPLASTY JI J. Arthroplast. PD OCT PY 2005 VL 20 IS 7 SU 3 BP 17 EP 25 DI 10.1016/j.arth.2005.04.021 PG 9 WC Orthopedics SC Orthopedics GA 982GP UT WOS:000233146400006 PM 16213998 ER PT J AU Zhang, JP Niaura, R Todaro, JF McCaffery, JM Shen, BJ Spiro, A Ward, KD AF Zhang, JP Niaura, R Todaro, JF McCaffery, JM Shen, BJ Spiro, A Ward, KD TI Suppressed hostility predicted hypertension incidence among middle-aged men: The normative aging study SO JOURNAL OF BEHAVIORAL MEDICINE LA English DT Article DE hostility; suppression; aging; incident hypertension ID CORONARY HEART-DISEASE; HIGH BLOOD-PRESSURE; DEFENSIVE HOSTILITY; CARDIOVASCULAR REACTIVITY; COPING STYLES; FOLLOW-UP; SOCIAL DESIRABILITY; CYNICAL HOSTILITY; ANGER EXPRESSION; YOUNG MEN AB This study tested whether suppressed hostility predicted incident hypertension (HTN) in initially nonhypertensive men, using prospective data from the Normative Aging Study. Six hundred twenty-seven men who completed the MMPI and participated in a subsequent laboratory assessment were included in the study. The Cook-Medley Hostility scale (Ho), a suppression factor, and other risk factors were used to predict incident HTN over a 3-year period. Logistic regression showed a significant three-way interaction among Ho, suppression, and age in predicting incident HTN. Among middle-aged men (<= 60 years) with higher suppression, a 1-point decrease in the Ho score was associated with an 18% increase in HTN risk. This relationship remained significant after controlling for relevant risk factors. Among older participants, the Ho x Suppression interaction was not predictive of HTN incidence. These results provide support for the Suppressed Hostility hypothesis in middle-aged men. C1 Indiana Univ Purdue Univ, Dept Psychol, Indianapolis, IN 46202 USA. Brown Univ, Sch Med, Providence, RI 02912 USA. Miriam Hosp, Providence, RI 02906 USA. Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. Boston VA Healthcare Syst, Boston, MA 02215 USA. Univ Memphis, Memphis, TN 38152 USA. RP Zhang, JP (reprint author), Indiana Univ Purdue Univ, Dept Psychol, 402 N Blackford St,LD 124, Indianapolis, IN 46202 USA. EM jzhang1@iupui.edu RI Zhang, Jianping/L-9805-2016 OI Zhang, Jianping/0000-0001-6363-6362 FU NHLBI NIH HHS [HL37871]; NIA NIH HHS [AG02287] NR 58 TC 7 Z9 7 U1 2 U2 8 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0160-7715 J9 J BEHAV MED JI J. Behav. Med. PD OCT PY 2005 VL 28 IS 5 BP 443 EP 454 DI 10.1007/s10865-005-9016-5 PG 12 WC Psychology, Clinical SC Psychology GA 996IJ UT WOS:000234167300005 PM 16179978 ER PT J AU Kaulin, YA Takemoto, JY Schagina, LV Ostroumova, OS Wangspa, R Teeter, JH Brand, JG AF Kaulin, YA Takemoto, JY Schagina, LV Ostroumova, OS Wangspa, R Teeter, JH Brand, JG TI Sphingolipids influence the sensitivity of lipid bilayers to fungicide, syringomycin E SO JOURNAL OF BIOENERGETICS AND BIOMEMBRANES LA English DT Article DE syringomycin E; ion channels; bilayer lipid membranes; sphingolipid; fungicide; Pseudomonas syringae ID SACCHAROMYCES-CEREVISIAE; PSEUDOMONAS-SYRINGAE; YEAST SPHINGOLIPIDS; PLASMA-MEMBRANE; CHANNELS; RECEPTORS; PHYTOTOXIN; MECHANISM; CELLS AB Sphingolipids with long chain bases hydroxylated at the C4 position are a requisite for the yeast, Saccharomyces cerevisia, to be sensitive to the ion channel forming antifungal agent, syringomycin E (SRE). A mutant S. cerevisiae strain, Delta syr2, having sphingolipids with a sphingoid base devoid of C4-hydroxylation, is resistant to SRE. To explore the mechanism of this resistance, we investigated the channel forming activity of SRE in lipid bilayers of varying composition. We found that the addition of sphingolipid-rich fraction from Delta syr2 to the membrane-forming solution (DOPS/DOPE/ergosterol) resulted in lipid bilayers with lower sensitivity to SRE compared with those containing sphingolipid fraction from wild-type S. cerevisiae. Other conditions being equal, the rate of increase of bilayer conductance was about 40 times slower, and the number of SRE channels was about 40 times less, with membranes containing Delta syr2 versus wild-type sphingolipids. Delta syr2 sphingolipids altered neither SRE single channel conductance nor the gating charge but the ability of SRE channels to open synchronously was diminished. The results suggest that the resistance of the Delta syr2 mutant to SRE may be partly due to the ability of sphingolipids without the C4 hydroxyl group to decrease the channel forming activity of SRE. C1 Monell Chem Senses Ctr, Philadelphia, PA 19104 USA. Russian Acad Sci, Inst Cytol, Philadelphia, PA 19104 USA. Utah State Univ, Dept Biol, Logan, UT 84322 USA. Univ Penn, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Philadelphia, PA USA. RP Kaulin, YA (reprint author), Thomas Jefferson Univ, Dept Pathol, Jefferson Med Coll, 1020 Locust St, Philadelphia, PA 19107 USA. EM yuri.kaulin@jefferson.edu; brand@monell.org RI Ostroumova, Olga/N-8636-2013; Takemoto, Jon/A-5309-2011 OI Takemoto, Jon/0000-0001-9919-9168 NR 30 TC 14 Z9 14 U1 0 U2 1 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0145-479X J9 J BIOENERG BIOMEMBR JI J. Bioenerg. Biomembr. PD OCT PY 2005 VL 37 IS 5 BP 339 EP 348 DI 10.1007/s10863-005-8645-2 PG 10 WC Biophysics; Cell Biology SC Biophysics; Cell Biology GA 992EX UT WOS:000233868300007 PM 16341778 ER EF