FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Rosovsky, RP Abdel-Wahad, OI Van Cott, EM Kuter, DJ AF Rosovsky, Rachel P. Abdel-Wahad, Omar I. Van Cott, Elizabeth M. Kuter, David J. TI The incidence of thrombosis in patients with isolated heparin induced thrombocytopenia. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Internal Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02114 USA. NR 0 TC 2 Z9 2 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 NOV 16 PY 2006 VL 108 IS 11 MA 1049 BP 312A EP 312A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440001308 ER PT J AU Toro, JJ Choa-Bayona, L Ahuja, SS Quinones, MP Lee, S Estrada, CA Freytes, CO AF Toro, Juan J. Choa-Bayona, Leonel Ahuja, Seema S. Quinones, Marlon P. Lee, Shuko Estrada, Carlos A. Freytes, Cesar O. TI Chemokine plasma concentration in patients with B-cell chronic lymphocytic leukemia. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 S Texas Vet Hlth Care Syst, San Antonio, TX USA. Univ Texas, Ctr Hlth Sci, San Antonio, TX 78285 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 4957 BP 326B EP 327B PN 2 PG 2 WC Hematology SC Hematology GA 111GW UT WOS:000242440402076 ER PT J AU Brown, JR Stock, W Katzen, HI Suarez, AJ Lakhanpal, S Leis, JF Flowers, C AF Brown, Jennifer R. Stock, Wendy Katzen, Harvey I. Suarez, Agustin J. Lakhanpal, Shailendra Leis, Jose F. Flowers, Christopher CA ECO-1 Study Investigators TI Early estimates of safety for alemtuzumab combined with fludarabine for the treatment of relapsed/refractory B-cell chronic lymphocytic leukemia: Phase II multicenter study. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Univ Chicago, Med Ctr & Hosp, Chicago, IL 60637 USA. Oncol Hematol Associates PA, Clinton, NY USA. LLC, New Orleans, LA USA. LLC, Birmingham, AL USA. Oregon Hlth Sci Univ, Hematol Malignancies Ctr, Portland, OR 97201 USA. Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA. RI Flowers, Christopher/F-1953-2010 OI Flowers, Christopher/0000-0002-9524-3990 NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 4989 BP 336B EP 336B PN 2 PG 1 WC Hematology SC Hematology GA 111GW UT WOS:000242440402108 ER PT J AU Kiziltepe, T Catley, L Hideshima, T Raje, N Yasui, H Vallet, S Ikeda, H Okawa, Y Anderson, KC AF Kiziltepe, Tanyel Catley, Laurence Hideshima, Teru Raje, Noopur Yasui, Hiroshi Vallet, Sonia Ikeda, Hiroshi Okawa, Yutaka Anderson, Kenneth C. TI Epigenetic modulation by Vidaza (TM) induces apoptosis and overcomes in vitro drug resistance in human multiple myeloma cells. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr Dept Med Oncol, Boston, MA 02115 USA. RI Catley, Laurence/E-5313-2013 NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 5001 BP 339B EP 339B PN 2 PG 1 WC Hematology SC Hematology GA 111GW UT WOS:000242440402120 ER PT J AU Podar, K Tonon, G Sattler, M Tai, YT LeGouill, S Yasui, H Ishitsuka, K Kumar, R Pandite, LN Hideshima, T Chauhan, D Anderson, KC AF Podar, Klaus Tonon, Giovanni Sattler, Martin Tai, Yu-Tzu LeGouill, Steven Yasui, Hiroshi Ishitsuka, Kenji Kumar, Rakesh Pandite, Lini N. Hideshima, Teru Chauhan, Dharminder Anderson, Kenneth C. TI The small-molecule VEGF-receptor inhibitor pazopanib (GW786034B) targets both tumor and endothelial cells in multiple myeloma. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. CHU, INSERM, Nantes, France. GlaxoSmithKline Inc, Res Triangle Pk, NC USA. NR 0 TC 1 Z9 1 U1 2 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 NOV 16 PY 2006 VL 108 IS 11 MA 5003 BP 339B EP 339B PN 2 PG 1 WC Hematology SC Hematology GA 111GW UT WOS:000242440402122 ER PT J AU Yasui, H Hideshima, T Ikeda, H Ocio, EM Kiziltepe, T Vallet, S Okawa, Y Chhetri, S Sukhdeo, K Ishitsuka, ' Podar, K Raje, N Chauhan, D Cattasco, DR Anderson, KC AF Yasui, Hiroshi Hideshima, Teru Ikeda, Hiroshi Ocio, Enrique M. Kiziltepe, Tanyel Vallet, Sonia Okawa, Yutaka Chhetri, Shweta Sukhdeo, Kumar Ishitsuka, 'Kenji Podar, Klaus Raje, Noopur Chauhan, Dharminder Cattasco, Daniel R. Anderson, Kenneth C. TI Novel etodolac analog SDX-308 (CEP-18082) induces cytotoxicity in multiple myeloma cells associated with inhibition of Wnt/beta-catenin pathway. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma, Boston, MA 02115 USA. Sapporo Med Univ, Dept Internal Med 1, Sapporo, Hokkaido, Japan. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 5005 BP 340B EP 340B PN 2 PG 1 WC Hematology SC Hematology GA 111GW UT WOS:000242440402124 ER PT J AU Mann, JJ Langer, NB Woo, A Moran, TB Schindler, Y Sullivan, M Paw, BH Cantor, AB AF Mann, James J. Langer, Nathaniel B. Woo, Andrew Moran, Tyler B. Schindler, Yocheved Sullivan, Matthew Paw, Barry H. Cantor, Alan B. TI Essential role of kindlin 3 in zebrafish thrombopoiesis. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Childrens Hosp Boston, Dana Farber Canc Inst, Harvard Med Sch, Div Pediat Hematol Oncol, Boston, MA USA. Brigham & Womens Hosp, Harvard Med Sch, Div Hematol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2006 VL 108 IS 11 MA 1166 BP 344A EP 344A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440001425 ER PT J AU Gastinne, T Leleu, X Moreau, AS Andrieux, J Lai, JL Coiteux, V Yakoub-Agha, I Bauters, F Moreau, P Harousseau, JL Facon, T Zandecki, M AF Gastinne, Thomas Leleu, Xavier Moreau, Anne-Sophie Andrieux, Joris Lai, Jean-Luc Coiteux, Valerie Yakoub-Agha, Ibrahim Bauters, Francis Moreau, Philippe Harousseau, Jean-Luc Facon, Thierry Zandecki, Marc TI Plasma cell proliferation using Ki67 antigen expression defines subgroups related to short survival in multiple myeloma especially with low beta-2 microglobulin. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 CHU Nantes, Serv Hematol Clin, F-44035 Nantes 01, France. CHU Lille, Serv Malad Sang, F-59037 Lille, France. CHU Lille, Gen Med Serv, F-59037 Lille, France. CHU Angers, Hematol Lab, Angers, France. Dana Farber Canc Inst, Boston, MA 02115 USA. RI FACON, THIERRY/M-9736-2014; richard, chrystelle/K-8595-2015 OI FACON, THIERRY/0000-0001-7705-8460; NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 5031 BP 346B EP 347B PN 2 PG 2 WC Hematology SC Hematology GA 111GW UT WOS:000242440402150 ER PT J AU Ishitsuka, K Hideshima, T Neri, P Vallet, S Shiraishi, N Raje, N Shen, Z Kiziltepe, T Ocio, EM Podar, K Chauhan, D Munshi, N Campbell, RM De Dios, A Shih, C Starling, JJ Tamura, K Anderson, KC AF Ishitsuka, Kenji Hideshima, Teru Neri, Paola Vallet, Sonia Shiraishi, Norihiko Raje, Noopur Shen, Zhenxin Kiziltepe, Tanyel Ocio, Enrique M. Podar, Klaus Chauhan, Dharminder Munshi, Nikhil Campbell, Robert M. De Dios, Alfonso Shih, Chuan Starling, James J. Tamura, Kazuo Anderson, Kenneth C. TI p38MAPK inhibitor LSN2322600 modulates the bone marrow microenvironment and inhibits osteoclastogenesis in multiple myeloma. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Dana Farber Canc Inst, Harvard Med Sch, Dept Med Oncol, Boston, MA 02115 USA. Fukuoka Univ, Dept Internal Med 1, Fukuoka 81401, Japan. Beth Israel Med Ctr, New England Baptist Bone & Joint Inst, Boston, MA USA. Eli Lilly & Co, Lilly Corp Ctr, Indianapolis, IN 46285 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 5042 BP 350B EP 350B PN 2 PG 1 WC Hematology SC Hematology GA 111GW UT WOS:000242440402161 ER PT J AU Driscoll, JJ Bertheau, RC Shammas, MA Prabhala, RH Anderson, KC Munshi, NC AF Driscoll, James J. Bertheau, Robert C. Shammas, Masood A. Prabhala, Rao H. Anderson, Kenneth C. Munshi, Nikhil C. TI Physical and functional association of the MRN complex with human telomerase in multiple myeloma. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 VA Boston Hlthcare Syst, W Roxbury, MA USA. Dana Farber Canc Inst, Harvard Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 5076 BP 358B EP 358B PN 2 PG 1 WC Hematology SC Hematology GA 111GW UT WOS:000242440402195 ER PT J AU Song, WH van der Vliet, HJJ Tai, YT Wang, R Prabhala, R Podar, K Catley, L Shammas, M Balk, SP Anderson, KC Exley, MA Munshi, NC AF Song, Weihua van der Vliet, Hans J. J. Tai, Yu-Tzu Wang, Ruojie Prabhala, Rao Podar, Klaus Catley, Laurence Shammas, Masood Balk, Steven P. Anderson, Kenneth C. Exley, Mark A. Munshi, Nikhil C. TI In vitro generation of highly purified functional invariant NKT cells in multiple myeloma: A strategy for immunotherapy. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dana Farber Canc Inst,Dept Med Oncol, Boston, MA 02215 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston VA Hlth Care Syst, Boston, MA USA. RI van der Vliet, Hans/B-1176-2013; Catley, Laurence/E-5313-2013 NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 5104 BP 365B EP 365B PN 2 PG 1 WC Hematology SC Hematology GA 111GW UT WOS:000242440402223 ER PT J AU Chong, Y Mizuno, SI Shigematsu, H Arinobu, Y Iino, T Iwasaki, H Akashi, K AF Chong, Yong Mizuno, Shin-ichi Shigematsu, Hirokazu Arinobu, Yojiro Iino, Tadafumi Iwasaki, Hiromi Akashi, Koichi TI In vivo permanent marking of cells with RAG1 activation history demonstrates only a minor contribution of the lymphoid pathway to dendritic cell development. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Kyushu Univ Hosp, Ctr Cellular & Mol Med, Fukuoka 812, Japan. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 1268 BP 372A EP 372A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440001527 ER PT J AU Mori, Y Iwasaki, H Yoshimoto, G Okeda, A Miyamoto, T Mizuno, SI Harada, M Takatsu, K Akashi, K AF Mori, Yasuo Iwasaki, Hiromi Yoshimoto, Goichi Okeda, Aki Miyamoto, Toshihiro Mizuno, Shin-ichi Harada, Mine Takatsu, Kiyoshi Akashi, Koichi TI Prospective isolation of human eosinophil-committed progenitors. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Kyushu Univ, Grad Sch Med Sci, Dept Med Biosyst Sci, Fukuoka 812, Japan. Kyushu Univ Hosp, Ctr Cellular & Mol Med, Fukuoka 812, Japan. Harvard Med Sch, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Univ Tokyo, Inst Med Sci, Dept Microbiol & Immunol, Tokyo, Japan. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 1285 BP 377A EP 377A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440001544 ER PT J AU Silberstein, LE Dykxhoom, D Le, Y Honczarenko, M Lieberman, J Glodek, A AF Silberstein, Leslie E. Dykxhoom, Derek Le, Yi Honczarenko, Marek Lieberman, Judy Glodek, Aleksandra TI Focal adhesion kinase (FAK) is required for CXCL12-Induced dhemotaxis and adhesion to VCAM-1 in B lymphocytes and hematopoietic stem/progenitor cells. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Childrens Hosp, Boston, MA 02115 USA. Inst Biomed Res, CBR, Boston, MA USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 1325 BP 388A EP 388A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440001584 ER PT J AU Xu, HM Szczur, K Zheng, Y Settleman, J Williams, DA Filippi, MD AF Xu, Haiming Szczur, Kathleen Zheng, Yi Settleman, Jeffrey Williams, David A. Filippi, Marie-Dominique TI P190-B RhoGAP is critical for hematopoietic stem/progenitor cell homing and short term engraftment. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Childrens Hosp, Med Ctr, Div Expt Hematol, Cincinnati, OH 45229 USA. Univ Cincinnati, Coll Med, Cell & Mol Biol Graduate Program, Cincinnati, OH USA. Massachusetts Gen Hosp, Ctr Canc, Harvard Med Sch, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2006 VL 108 IS 11 MA 1341 BP 392A EP 392A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440001600 ER PT J AU Vasir, B Lenahan, C Rosenblatt, J Bissonnette, A Wu, ZK Kufe, D Avigan, D AF Vasir, Baldev Lenahan, Corrine Rosenblatt, Jacalyn Bissonnette, Adam Wu, Zekui Kufe, Donald Avigan, David TI Stimulation of anti-tumor immunity using dendritic cells transduced with fowl pox vector expressing MUC-1 and costimulatory molecules (PANVAC-F). SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 5209 BP 393B EP 393B PN 2 PG 1 WC Hematology SC Hematology GA 111GW UT WOS:000242440402327 ER PT J AU Schittenhelm, MM Yee, KW Kampa, KM Heinrich, MC AF Schittenhelm, Marcus M. Yee, Kevin W. Kampa, Kerstin M. Heinrich, Michael C. TI Tandutinib (MLN518), a potent FLT3 inhibitor, synergizes with cytarabine and/or daunorubicin in a sequence-independent manner. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Univ Tubingen, Dept Hematol Oncol Rheumatol Immunol & Pulm, Tubingen, Germany. OHSU Canc Inst, Dept Med, Portland, OR USA. Portland VA Med Ctr, Portland, OR USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2006 VL 108 IS 11 MA 1374 BP 401A EP 401A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440001633 ER PT J AU Ghazi, A Griesemer, A Okumi, M Hirsh, E Lo, D Sykes, M Sachs, DH Yamada, K Huang, CA AF Ghazi, Ahmed Griesemer, Adam Okumi, Masayoshi Hirsh, Erica Lo, Diana Sykes, Megan Sachs, David H. Yamada, Kazuhiko Huang, Christene A. TI Specific non-responsiveness to pig in baboons receiving BMT from GaIT-KO pigs. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 5265 BP 408B EP 408B PN 2 PG 1 WC Hematology SC Hematology GA 111GW UT WOS:000242440402383 ER PT J AU O'Neil, J Tchinda, J Gutierrez, A Moreau, L McKenna, K Maser, R Wong, KK Wu, WS DePinho, R Chin, L Lee, C Look, AT AF O'Neil, Jennifer Tchinda, Joelle Gutierrez, Alejandro Moreau, Lisa McKenna, Keith Maser, Richard Wong, Kwok-Kin Wu, Wenshu DePinho, Ronald Chin, Lynda Lee, Charles Look, A. Thomas TI Large scale copy number variation upregulates the expression of MYB in human T-ALL. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 1408 BP 409A EP 410A PN 1 PG 2 WC Hematology SC Hematology GA 111GS UT WOS:000242440001667 ER PT J AU Rhodes, J Amsterdam, A Ho, K Heinrichs, S Kinki, JP O'Neil, JE Gutierrez, A McKenna, K Feng, H Fleming, M Neuberg, D Galinsky, I Stone, RM Hopkins, N Look, AT AF Rhodes, Jennifer Amsterdam, Adam Ho, Karen Heinrichs, Stefan Kinki, John P. O'Neil, Jennifer E. Gutierrez, Alejandro McKenna, Keith Feng, Hui Fleming, Mark Neuberg, Donna Galinsky, Ilene Stone, Richard M. Hopkins, Nancy Look, A. Thomas TI Emi1 is required for normal cell cycle progression in zebrafish myelopoiesis and likely functions as a haploinsufficient tumor suppressor on chromosome 6q in human leukmias. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. MIT, Cambridge, MA 02139 USA. Childrens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 1405 BP 409A EP 409A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440001664 ER PT J AU Sweetser, DA Dayyani, F Wang, JF Zhang, YT Zaidi, T AF Sweetser, David A. Dayyani, Farshid Wang, Jianfeng Zhang, Yuntian Zaidi, Tanweer TI The groucho corepressors, TLE1 and TLE4, are candidate del(9q) AML tumor suppressor genes that can complement AML1-ETO. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 1406 BP 409A EP 409A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440001665 ER PT J AU Ma, Y Yang, JC Chai, L Liu, F Amin, HM AF Ma, Yupo Yang, Jianchang Chai, Li Liu, Fang Amin, Hesham M. TI Bmi1 - Is a SALL4 target gene in hematopoeitic and leukemic cells. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Nevada Canc Inst, Div Lab Med, Las Vegas, NV USA. Brigham & Womens Hosp, Joint Program Transfus Med, Boston, MA 02115 USA. Childrens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Texas, MD Anderson Canc Ctr, Dept Hematopathol, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 1411 BP 410A EP 410A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440001670 ER PT J AU Draheim, KM Sharma, VM Calvo, JA Cunningham, LA Hermance, N Krishnamoorthy, V Beverly, L Bhasin, M Capobianco, A Kelliher, MA AF Draheim, Kyle M. Sharma, Vishva M. Calvo, Jennifer A. Cunningham, Leslie A. Hermance, Nicole Krishnamoorthy, Veena Beverly, Levi Bhasin, Manoj Capobianco, Anthony Kelliher, Michelle A. TI Notch1 provides a proliferative signal in mouse T cell leukemia by directly targeting c-Myc. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Univ Massachusetts, Ctr Canc, Dept Canc Biol, Worcester, MA 01605 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Wistar Inst Anat & Biol, Mol Cellular Oncogenesis Program, Philadelphia, PA USA. Novartis Inc, Diabetes Div, Cambridge, MA USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 1434 BP 416A EP 416A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440001693 ER PT J AU Sidi, S Hagen, AT Kennedy, R Imamura, S Kishi, S Kanki, J D'Andrea, A Look, AT AF Sidi, Samuel Hagen, Andreas T. Kennedy, Richard Imamura, Shintaro Kishi, Shuji Kanki, John D'Andrea, Alan Look, A. Thomas TI Modifier genetics in zebrafish identify Chk1 and an associated survival pathway as targets for pharmacotherapy of MDS/AML with P53 mutations. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 1432 BP 416A EP 416A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440001691 ER PT J AU Klement, GL Cervi, D Yip, TT Folkman, J Italiano, J AF Klement, Giannoula L. Cervi, David Yip, Tai-Tung Folkman, Judah Italiano, Joseph TI Platelet PF-4 is an early marker of tumor angiogenesis. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Childrens Hosp, Dept Surg, Vasc Biol Program, Boston, MA 02115 USA. Harvard Univ, Boston, MA 02115 USA. Ciphergen Biosyst Inc, Fremont, CA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2006 VL 108 IS 11 MA 1476 BP 426A EP 427A PN 1 PG 2 WC Hematology SC Hematology GA 111GS UT WOS:000242440001735 ER PT J AU Flaumenhaft, R Dilks, JR Patel, SR Klement, G Italiano, JE AF Flaumenhaft, Robert Dilks, James R. Patel, Sunita R. Klement, Giannoula Italiano, Joseph E. TI Megakaryocyte-derived microparticles: Mechanism of formation and circulation in plasma. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Beth Israel Deaconess Med Ctr, Div Hemostasis & Thrombosis, Boston, MA 02215 USA. Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 1507 BP 435A EP 435A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440002024 ER PT J AU Park, JH Yee, AJ Spitzer, TR Saidman, SL Ting, DT Pannone, A Reid, J McAfee, S Dey, BR AF Park, Jae H. Yee, Andrew J. Spitzer, Thomas R. Saidman, Susan L. Ting, David T. Pannone, Andrea Reid, Jessica McAfee, Steven Dey, Bimalangshu R. TI KIR ligand incompatibility in HLA-Identical sibling nonmyeloablative hematopoietic stem cell transplantation for hematologic malignancies. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Massachusetts Gen Hosp, Harvard Med Sch, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 5371 BP 436B EP 436B PN 2 PG 1 WC Hematology SC Hematology GA 111GW UT WOS:000242440402488 ER PT J AU Reheman, A Hong, Y Spring, CM Chen, P Wagner, DD Fassler, R Freedman, J Ni, H AF Reheman, Adili Hong, Yang Spring, Christopher M. Chen, Pingguo Wagner, Denisa D. Fassler, Reinhard Freedman, John Ni, Heyu TI Fibronectin is not the only important molecule required for fibrinogen/VWF-independent platelet aggregation: Study of thrombosis in a new strain of triple deficient mice. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada. St Michaels Hosp, Dept Lab Med, Toronto Platelet Immunobiol Grp, Toronto, ON M5B 1W8, Canada. Harvard Univ, Sch Med, CBR Inst Biomed Res, Dept Pathol, Boston, MA USA. Max Planck Inst Biochem, Dept Mol Med, D-82152 Martinsried, Germany. Univ Toronto, Dept Med, Toronto, ON, Canada. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 1515 BP 436A EP 436A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440002031 ER PT J AU Schiller, GJ Sohn, JP Malone, R Bartone, K Habtemariam, B Paquette, R De Vos, S Territo, M AF Schiller, Gary J. Sohn, J. Phillip Malone, R. Bartone, K. Habtemariam, B. Paquette, R. De Vos, Sven Territo, M. TI Phase I/II trial of bortezomib maintenance following autolgous peripheral blood progenitor cell transplantation as treatment for intermediate- and advanced-stage multiple myeloma. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Calif State Univ Los Angeles, David Greffen Sch Med, Dept Med, Los Angeles, CA 90032 USA. VA Greater Los Angeles Healthcare Ctr, Los Angeles, CA USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 5433 BP 453B EP 453B PN 2 PG 1 WC Hematology SC Hematology GA 111GW UT WOS:000242440402550 ER PT J AU Vallet, S Raje, N Ishitsuka, K Hideshima, T Podar, K Veiby, P Breitkreutz, I Kizeltepe, T Yasui, H Ocio, EM Shiraishi, N Ladetto, M Boccadoro, M Anderson, KC AF Vallet, Sonia Raje, Noopur Ishitsuka, Kenji Hideshima, Tern Podar, Klaus Veiby, Petter Breitkreutz, Iris Kizeltepe, Tanyel Yasui, Hiroshi Ocio, Enrique M. Shiraishi, Norihiko Ladetto, Marco Boccadoro, Mario Anderson, Kenneth C. TI MLN3897, a novel CCR1 antagonist, inhibits osteoclastogenesis by blocking early ERK activation. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Harvard Med Sch, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Dis Ctr, Boston, MA USA. Univ Turin, Cattedra Ematol, Dipartimento Med & Oncol Sperimentale, Turin, Italy. Millennium Pharmaceut, Cambridge, MA USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 1636 BP 467A EP 467A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440002152 ER PT J AU Kikushige, Y Yoshimoto, G Miyamoto, T Ishikawa, F Iwasaki, H Harada, M Akashi, K AF Kikushige, Yoshikane Yoshimoto, Goichi Miyamoto, Toshihiro Ishikawa, Fumihiko Iwasaki, Hiromi Harada, Mine Akashi, Koichi TI hF113 expression marks long-term hematopoietic stem cells, but not the pathway common to granulocyte/monocyte and lymphoid lineages in human hematopoiesis. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Kyushu Univ, Grad Sch Med Sci, Fukuoka 812, Japan. Kyushu Univ Hosp, Ctr Cellular & Mol Med, Fukuoka 812, Japan. Yokohama Inst, RIKEN, Res Unit Human Dis Model, Yokohama, Kanagawa, Japan. Harvard Med Sch, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 1654 BP 471A EP 472A PN 1 PG 2 WC Hematology SC Hematology GA 111GS UT WOS:000242440002170 ER PT J AU Arinobu, Y Mizuno, SI Shigematsu, M Ozawa, H Chong, Y Iwasaki, H Kastner, P Chan, S Akashi, K AF Arinobu, Yojiro Mizuno, Shin-Ichi Shigematsu, Hirokazu Ozawa, Hidetoshi Chong, Yong Iwasaki, Hirorni Kastner, Philippe Chan, Susan Akashi, Koichi TI Delineation of the common developmental pathway for granulocyte/monocyte and lymphoid lineages by using an expression reporter for PU.1. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Inst Genet & Biol Mol & Cellulaire, Illkirch Graffenstaden, France. Kyushu Univ Hosp, Ctr Cellular & Mol Med, Fukuoka 812, Japan. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2006 VL 108 IS 11 MA 1656 BP 472A EP 472A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440002172 ER PT J AU Chu, JT Burdick, MM Sackstein, R AF Chu, Julia T. Burdick, Monica M. Sackstein, Robert TI HCELL is the major E- and L-selectin ligand expressed on human hematopoietic progenitor cells and colon carcinoma cells. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 1675.5 BP 477A EP 478A PN 1 PG 2 WC Hematology SC Hematology GA 111GS UT WOS:000242440002193 ER PT J AU Lafuente, EM Salanga, M Iwamoto, Y Li, LQ Boussiotis, VA AF Lafuente, Esther M. Salanga, Mathew Iwamoto, Yoshiko Li, Lequn Boussiotis, Vassiliki A. TI RIAM regulates actin reorganization at the immunological synapse and calcium mobilization during T cell activation. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02114 USA. Childrens Hosp, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Lafuente, Esther M/K-5684-2014 OI Lafuente, Esther M/0000-0001-8466-1022 NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 1722 BP 489A EP 489A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440002240 ER PT J AU Chauhan, AK Kisucka, J Lamb, CB Bergmeier, W Wagner, DD AF Chauhan, Anil K. Kisucka, Janka Lamb, Colin B. Bergmeier, Wofgang Wagner, Denisa D. TI von Willebrand factor and factor VIII are independently required to form stable occlusive thrombi in injured veins. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Harvard Univ, Sch Med, Dept Pathol, Inst Biomed Res CBR, Boston, MA 02115 USA. CBR, Biomed Res Inst, Boston, MA USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 1789 BP 508A EP 508A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440002307 ER PT J AU Bergmeier, W Piffath, CL Goerge, T Cifuni, SM Ruggeri, ZM Ware, J Wagner, DD AF Bergmeier, Wolfgang Piffath, Crystal L. Goerge, Tobias Cifuni, Stephen M. Ruggeri, Zaverio M. Ware, Jerry Wagner, Denisa D. TI The role of platelet adhesion receptor GPIb alpha far exceeds that of its main ligand von Willebrand factor in arterial thrombosis. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 CBR, CBR Biomed Res Inst, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Scripps Res Inst, La Jolla, CA USA. Univ Arkansas Med Sci, Little Rock, AR 72205 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 1797 BP 510A EP 510A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440002315 ER PT J AU Zhang, XF Wang, JF Maor, YS Kunos, G Groopman, JE AF Zhang, Xuefeng Wang, Jian Feng Maor, Yehoshua Kunos, George Groopman, Jerome E. TI Endogenous cannabinoid-like arachidonoyl serine protects against LPS-induced endothelial apoptosis. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Harvard Univ, Sch Med, BIDMC, Div Expt Med, Boston, MA USA. Harvard Univ, Sch Med, BIDMC, Dept Surg, Boston, MA USA. Hebrew Univ Jerusalem, Dept Med Chem & Nat Prod, Jerusalem, Israel. NIH, NIAAA, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2006 VL 108 IS 11 MA 1808 BP 513A EP 513A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440002326 ER PT J AU Chen, JH Jette, C Kanki, JP Aster, J Look, AT Griffin, JD AF Chen, Jihua Jette, Cicely Kanki, John P. Aster, Jon Look, A. Thomas Griffin, James D. TI NOTCH1-induced T-cell leukemia in transgenic zebrafish. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 1825 BP 517A EP 517A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440002343 ER PT J AU Mody, R Dover, D Yasui, Y Sallan, S Robison, L Neglia, J Boxer, L AF Mody, Rajen Dover, Douglas Yasui, Yutaka Sallan, Stephen Robison, Leslie Neglia, Joseph Boxer, Laurence TI Twenty year follow up of survivors of childhood acute lymphoid leukemia: A report from the childhood cancer survivor study (CCSS). SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Univ Michigan, Ann Arbor, MI 48109 USA. Univ Alberta, Edmonton, AB, Canada. DFCI, Boston, MA USA. St Jude Childrens Res Hosp, Memphis, TN 38105 USA. Univ Minnesota, Minneapolis, MN USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 1823 BP 517A EP 517A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440002341 ER PT J AU Feng, H Langenau, DM Kilgore, JA Quinkertz, A Jette, CA Neuberg, DS Campos-Ortega, JA Kanki, JP Look, T AF Feng, Hui Langenau, David M. Kilgore, Jennifer A. Quinkertz, Andre Jette, Cicely A. Neuberg, Donna S. Campos-Ortega, Jose A. Kanki, John P. Look, Thomas TI Bcl2 accelerates onset but not progression of MYC-induced T-cell leukemia in transgenic zebrafish. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Cologne, Inst Dev Biol, Cologne, Germany. Harvard Univ, Childrens Hosp, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 1829 BP 518A EP 518A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440002347 ER PT J AU Hirose, K Inukai, T Akahane, K Zhang, X Kuroda, I Honna, H Goi, K Inaba, T Look, AT Nakazawa, S Sugita, K AF Hirose, Kinuko Inukai, Takeshi Akahane, Koshi Zhang, Xiaochun Kuroda, Itaru Honna, Hiroko Goi, Kumiko Inaba, Toshiya Look, A. Thomas Nakazawa, Shinpei Sugita, Kanji TI E2A-HLF fusion transcription factor mediating aberrant expression of LMO2 in B-precursor ALL with t(17;19). SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Yamanashi Univ, Yamanashi, Japan. Hiroshima Univ, Hiroshima, Japan. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2006 VL 108 IS 11 MA 1832 BP 519A EP 519A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440002350 ER PT J AU Silverman, LB Stevenson, K Neuberg, D O'Brien, J Supko, J Sallan, SE AF Silverman, Lewis B. Stevenson, Kristen Neuberg, Donna O'Brien, Jane Supko, Jeffrey Sallan, Stephen E. TI Intravenous PEG asparaginase during remission induction for childhood ALL. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 1854 BP 525A EP 525A PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440002372 ER PT J AU DeAngelo, DJ Silverman, LB Couban, S Dahlberg, S Amrein, PC Seftel, MD Turner, AR Wadleigh, M Sirulnik, LA Galinsky, I Sallan, SE Stone, RM AF DeAngelo, Daniel J. Silverman, Lewis B. Couban, Stephen Dahlberg, Suzanne Amrein, Philip C. Seftel, Matthew D. Turner, A. Robert Wadleigh, Martha Sirulnik, L. Andres Galinsky, Ilene Sallan, Stephen E. Stone, Richard M. TI A multicenter phase II study using a dose intensified pediatric regimen in adults with untreated acute lymphoblastic leukemia. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NCI, Clin Trials Grp, Kingston, ON, Canada. Massachusetts Gen Hosp, Boston, MA 02114 USA. Canc Care Manitoba, Winnipeg, MB, Canada. Cross Canc Inst, Edmonton, AB, Canada. NR 0 TC 5 Z9 5 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 NOV 16 PY 2006 VL 108 IS 11 MA 1858 BP 526A EP 526A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440002376 ER PT J AU Silverman, LB Neuberg, D Supko, J Relling, M Woodward, C Sallan, SE AF Silverman, Lewis B. Neuberg, Donna Supko, Jeffrey Relling, Mary Woodward, Christina Sallan, Stephen E. TI Pharmacodynamics and tolerability of twice-weekly Erwinia asparaginase after E. coli asparaginase allergy in children with ALL. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. St Jude Childrens Res Hosp, Memphis, TN 38105 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 1857 BP 526A EP 526A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440002375 ER PT J AU Gadhoum, SZ Sackstein, R AF Gadhoum, Samah Z. Sackstein, Robert TI CD15 (Lewis x) expression in human myeloid cell differentiation is regulated by sialidase activity. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Brigham & Womens Hosp, Harvard Skin Dis Res Ctr, Dept Dermatol, Boston, MA USA. Harvard Med Sch, Boston, MA USA. Dana Farber Canc Inst, Dept Oncol, Boston, MA USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 1931 BP 546A EP 547A PN 1 PG 2 WC Hematology SC Hematology GA 111GS UT WOS:000242440002449 ER PT J AU Santana-Lemos, BAA Guibal, F Pintao, MC Scheucher, PS Abreu-Lima, RS Teixeira, HLG Pandolfi, PP Tenen, DG Rego, EM AF Santana-Lemos, Barbara A. A. Guibal, Florence Pintao, Maria-Carolina Scheucher, Priscila S. Abreu-Lima, Rodrigo S. Teixeira, Hamilton L. G. Pandolfi, Pier Paolo Tenen, Daniel G. Rego, Eduardo M. TI In vivo analysis of the role of C/EBP alpha in acute promyelocytic leukemia genesis. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Univ Sao Paulo, FMRP, BR-14049 Ribeirao Preto, Brazil. Harvard Inst Med, BIDMC, Boston, MA USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RI Scheucher, Priscila/F-1599-2013; Teixeira, Hamilton/E-5602-2013; Rego, Eduardo/A-1058-2012 OI Teixeira, Hamilton/0000-0001-6531-8587; Rego, Eduardo/0000-0003-1567-4086 NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 1937 BP 548A EP 548A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440002455 ER PT J AU Heinrichs, S Brenner, CJ Kulkami, RV Look, AT AF Heinrichs, Stefan Brenner, Chad J. Kulkami, Rima V. Look, A. Thomas TI MEIS1 is a required transcription factor for AML cell proliferation. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 1944 BP 550A EP 550A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440002462 ER PT J AU Giles, FJ Stock, W Vey, N Sciter, K DeAngelo, DJ Boskovic, D Stuart, RK Johnson, B Cahill, AL O'Brien, S AF Giles, Francis J. Stock, Wendy Vey, Norbert Sciter, Karen DeAngelo, Daniel J. Boskovic, Darinka Stuart, Robert K. Johnson, Bonny Cahill, Ann L. O'Brien, Susan TI A double blind placebo-controlled randomized phase III study of high dose continuous infusion cytosine arabinoside (araC) with or without cloretazine (R) in patients with first relapse of acute myeloid leukemia (AML). SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Univ Texas, MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA. Univ Chicago, Chicago, IL 60637 USA. Inst J Paoli I Calmettes, F-13009 Marseille, France. New York Med Coll, Valhalla, NY 10595 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Ctr Clin, Belgrade, Serbia. Hollings Canc Ctr, Charleston, SC USA. Vion Pharmaceut Inc, New Haven, CT USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 1970 BP 557A EP 557A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440002488 ER PT J AU Menzin, J Boulanger, L Karsten, V Cahill, AL Earle, CE AF Menzin, Joseph Boulanger, Luke Karsten, Verena Cahill, Ann L. Earle, Craig E. TI Effects of initial treatment on survival among elderly AML patients: Findings from the SEER-medicare database. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Boston Hlth Econom Inc, Waltham, MA 02115 USA. Vion Pharmaceut Inc, New Haven, CT USA. Dana Farber Canc Inst, Dept Med, Boston, MA USA. NR 0 TC 4 Z9 4 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 NOV 16 PY 2006 VL 108 IS 11 MA 1973 BP 558A EP 558A PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440002493 ER PT J AU Stubbs, MC Kim, T Krivtsov, A Atadja, P Armstrong, SA Kung, AL AF Stubbs, Matthew C. Kim, Teresa Krivtsov, Andrei Atadja, Peter Armstrong, Scott A. Kung, Andrew L. TI Induction of Bim facilitates apoptosis in leukemia cells treated with HDAC inhibitors. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Childrens Hosp, Div Hematol & Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA USA. Harvard Med Sch, Boston, MA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2006 VL 108 IS 11 MA 1994 BP 564A EP 564A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440002514 ER PT J AU Doolittle, ND Abrey, L Shenkier, T Siegal, T Bromberg, J Neuwelt, E Soussain, C Johnston, P Illerhaus, G Schiff, D Batchelor, T Montoto, S Zucca, E Kraemer, D AF Doolittle, Nancy D. Abrey, Lauren Shenkier, Tamara Siegal, Tali Bromberg, Jacoline Neuwelt, Edward Soussain, Carole Johnston, Patrick Illerhaus, Gerald Schiff, David Batchelor, Tracy Montoto, Silvia Zucca, Emanuele Kraemer, Dale TI Isolated brain parenchyma relapse of non-hodgkin's lymphoma (NHL): A descriptive analysis from the international primary CNS lymphoma collaborative group (IPCG). SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Oregon Hlth Sci Univ, Portland, OR 97201 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ British Columbia, Canc Agcy, Vancouver, BC V5Z 1M9, Canada. Hadassah Hebrew Univ Hosp, Jerusalem, Israel. Dr Daniel Den Hoed Canc Ctr, NL-3008 AE Rotterdam, Netherlands. ErasmusMC Univ Med Ctr, NL-3008 AE Rotterdam, Netherlands. Ctr Rene Huguenin, St Cloud, France. Mayo Clin, Rochester, MN USA. Univ Freiburg, Freiburg, Germany. Univ Virginia Neurol Ctr, Charlottesville, VA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. St Bartholomews Hosp, London, England. Oncol Inst So Switzerland, Bellinzona, Switzerland. Oregon State Univ, Portland, OR USA. NR 0 TC 0 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2006 VL 108 IS 11 MA 2026 BP 574A EP 574A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440002546 ER PT J AU Oton, AB Wang, H Melhem, M George, D Ghobrial, IM AF Oton, Ana B. Wang, Hong Melhem, Mona George, Diane Ghobrial, Irene M. TI Clinical and pathological prognostic markers for survival in adult patients with post-transplant lymphoproliferative disorders (PTLD), BCL2 is a poor prognostic marker in PTLD. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. Dana Farber Canc Inst, Harvard Med Sch, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 2035 BP 576A EP 576A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440002555 ER PT J AU Shammas, MA Bertheau, RC Koley, H Neri, P Tassone, P Batchu, RB Munshi, NC AF Shammas, Masood A. Bertheau, Robert C. Koley, Hemanta Neri, Paola Tassone, Pierfrancesco Batchu, Ramesh B. Munshi, Nikhil C. TI Elevated apurinic/apyrimidinic endonuclease activity significantly contributes to DNA instability in multiple myeloma. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 VA Hlth Care Syst, W Roxbury, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Med Sch, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 2077 BP 588A EP 588A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440002597 ER PT J AU Shammas, MA Bertheau, RC Munshi, V Patel, L Prabhala, R Desarnaud, F Driscoll, J Munshi, NC AF Shammas, Masood A. Bertheau, Robert C. Munshi, Vidit Patel, Laju Prabhala, Rao Desarnaud, Frank Driscoll, James Munshi, Nikhil C. TI Critical role of recombinase (HsRAD51) in genetic instability in multiple myeloma. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Harvard Med Sch, W Roxbury, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 2078 BP 589A EP 589A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440002598 ER PT J AU Koschmieder, S Agrawal, S Radomska, HS Huettner, CS Tenen, DG Ottmann, OG Berdel, WE Serve, HL Mueller-Tidow, C AF Koschmieder, Steffen Agrawal, Shuchi Radomska, Hanna S. Huettner, Claudia S. Tenen, Daniel G. Ottmann, Oliver G. Berdel, Wolfgang E. Serve, Hubert L. Mueller-Tidow, Carsten TI Decitabine and vitamin D3 differentially increase C-Jun, PU.1, and Sp1 hematopoietic transcription factors to induce monocytic differentiation. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Univ Hosp Muenster, Munster, Germany. Harvard Inst Med, BIDMC, Boston, MA USA. Blood Ctr Wisconsin, Milwaukee, WI USA. Univ Hosp Frankfurt, Frankfurt, Germany. RI Ottmann, Oliver/D-5007-2016 OI Ottmann, Oliver/0000-0001-9559-1330 NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 2223 BP 630A EP 630A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440003014 ER PT J AU Heinrich, MC Morich, JR Beillard, EJ Fuller, C Galderisi, CD Druker, BJ AF Heinrich, Michael C. Morich, Jason R. Beillard, Emmanuel J. Fuller, Courtney Galderisi, Chad D. Druker, Brian J. TI A novel, high-throughput assay for detection of ABL T315I mutations. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Portland VA Med Ctr, OHSU Canc Inst, Dept Med, Portland, OR USA. Molecular MD, Portland, OR USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 2334 BP 661A EP 661A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440003125 ER PT J AU Mueller, MR Sasaki, Y Sharma, S Rajewsky, K Rao, A AF Mueller, Martin R. Sasaki, Yoshiteru Sharma, Sonia Rajewsky, Klaus Rao, Anjana TI The role of the transcription factor NFAT in the pathogenesis of Non-Hodgkin's lymphomas. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Dept Pathol, Boston, MA USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 2371 BP 672A EP 672A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440003162 ER PT J AU Leleu, X Ngo, H Jia, X Moreau, AS Hatjiharisi, E Carrasco, R O'Sullivan, G Runnels, J Tai, YT Treon, S Hideshima, T Anderson, K Ghobrial, I AF Leleu, Xavier Ngo, Hai Jia, Xiaoying Moreau, Anne-Sophie Hatjiharisi, Evdoxia Carrasco, Ruben O'Sullivan, Garrett Runnels, Judith Tai, Yu-Tsu Treon, Steven Hideshima, Teru Anderson, Kenneth Ghobrial, Irene TI Molecular mechanisms regulating resistance to the akt inhibitor perifosine in waldenstrom's macroglobulinemia, the role of the ERK and PKC pathways. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. CHRU, Serv Maladies Sang, Lab Immunol, Lille, France. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 2416 BP 683A EP 684A PN 1 PG 2 WC Hematology SC Hematology GA 111GS UT WOS:000242440003207 ER PT J AU Leleu, X Ngo, H Runnels, J Pitsillides, C Spencer, J Moreau, AS Hatjiharisi, E Jia, X O'Sullivan, G Treon, S Hideshima, T Lin, C Anderson, K Ghobrial, I AF Leleu, Xavier Ngo, Hai Runnels, Judy Pitsillides, Costas Spencer, Joel Moreau, Anne-Sophie Hatjiharisi, Evdoxia Jia, Xiaoying O'Sullivan, Garrett Treon, Steven Hideshima, Teru Lin, Charles Anderson, Kenneth Ghobrial, Irene TI The PI3K/Akt pathway is an important regulator of homing and adhesion in waldenstrom's macroglobulinemia. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. Massachusetts Gen Hosp, Wellman Labs, Boston, MA 02114 USA. CHRU, Serv Maladies Sang, Lab Immunol, Lille, France. RI Spencer, Joel/A-4590-2013 NR 0 TC 1 Z9 1 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 NOV 16 PY 2006 VL 108 IS 11 MA 2417 BP 684A EP 684A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440003208 ER PT J AU Ngo, H Hatjiharissi, E Leleu, X Runnels, J Moreau, AS Jia, XY O'Sullivan, G Santos, D Xu, L Treon, S Hideshima, T Anderson, K Ghobrial, I AF Ngo, Hai Hatjiharissi, Evdoxia Leleu, Xavier Runnels, Judith Moreau, Anne-Sophie Jia, Xiaoying O'Sullivan, Garrett Santos, Daniel Xu, Lian Treon, Steven Hideshima, Teru Anderson, Kenneth Ghobrial, Irene TI The CXCR4/SDF-1 axis regulates migration and adhesion in waidenstrom macroglobu linemia. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. CHRU, Serv Maladies Sang, Lab Immunol, Lille, France. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 2418 BP 684A EP 684A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440003209 ER PT J AU Moreau, AS Leleu, X Manning, R Coiteux, V Darre, S Hatjiharisi, E Hunter, Z Jia, XY Ngo, H O'Sullivan, G Santos, D Treon, S Facon, T Anderson, K Ghobrial, I AF Moreau, Anne-Sophie Leleu, Xavier Manning, Robert Coiteux, Valerie Darre, Stephane Hatjiharisi, Evdoxia Hunter, Zachary Jia, Xiaoying Ngo, Hai O'Sullivan, Garrett Santos, Daniel Treon, Steven Facon, Thierry Anderson, Kenneth Ghobrial, Irene TI Serum free light chain in waldenstrom macroglobulinemia. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. CHRU, Serv Maladies Sang, Immunol Lab, Lille, France. RI Hunter, Zachary/H-3018-2013; FACON, THIERRY/M-9736-2014 OI Hunter, Zachary/0000-0002-1689-1691; FACON, THIERRY/0000-0001-7705-8460 NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2006 VL 108 IS 11 MA 2420 BP 685A EP 685A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440003211 ER PT J AU Foss, FM Sjak-Shie, N Goy, A Advani, R Jacobsen, E Acosta, M AF Foss, Francine M. Sjak-Shie, Nelida Goy, Andre Advani, Ranjana Jacobsen, Eric Acosta, Mark TI A phase II study of derdleukin diftitox (Ontak (R)) with CHOP chemotherapy in patients with newly-diagnosed aggressive T-cell lymphomas, the CONCEPT trial: Interim analysis. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Yale Med Sch, Yale Canc Ctr, New Haven, CT USA. US Oncol, St Louis, MO USA. Hackensack Univ, Med Ctr, Hackensack, NJ USA. Stanford Univ, Stanford, CA 94305 USA. Childrens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Ligand Pharmaceut, San Diego, CA USA. NR 0 TC 3 Z9 3 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 NOV 16 PY 2006 VL 108 IS 11 MA 2461 BP 696A EP 697A PG 2 WC Hematology SC Hematology GA 111GS UT WOS:000242440003251 ER PT J AU Treon, SP Soumerai, JD Patterson, CJ Hunter, ZR Villarreal, R Ghobrial, IM AF Treon, Steven P. Soumerai, Jacob D. Patterson, Christopher J. Hunter, Zachary R. Villarreal, Rose Ghobrial, Irene M. TI Imatinib mesylate (Gleevec (R)) is active in relapsed/refractory Waldenstrom's macroglobulinemia: Planned interim results of WMCTG clinical trial 05-140. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Dana Farber Canc Inst, Harvard Med Sch, Bing Ctr Waldenstroms Macroglobulinemia, Boston, MA 02115 USA. RI Hunter, Zachary/H-3018-2013 OI Hunter, Zachary/0000-0002-1689-1691 NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2006 VL 108 IS 11 MA 2484 BP 704A EP 704A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440003274 ER PT J AU Hatjiharissi, E Ho, AW Xu, L O'Connor, KE Hunter, ZR Santos, DD Manning, R Leleu, X Moreau, AS Patterson, CJ McEarchern, JA Grewal, IS Munshi, NC Treon, SP AF Hatjiharissi, Evdoxia Ho, Allen W. Xu, Lian O'Connor, Kelly E. Hunter, Zachary R. Santos, Daniel D. Manning, Robert Leleu, Xavier Moreau, Anne-Sphie Patterson, Christopher J. McEarchern, Julie A. Grewal, Iqbal S. Munshi, Nikhil C. Treon, Steven P. TI Preclinical in vitro and in vivo evidence support a therapeutic role for the CD70 directed monoclonal antibody (SGN-70) in Waldenstrom's macroglobulinemia (WM). SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Dana Farber Canc Inst, Harvard Med Sch, Bing Ctr Waldenstroms Macroglobulinemia, Boston, MA 02115 USA. Dana Farber Canc Inst, Harvard Med Sch, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. Seattle Genet Inc, Bothell, WA USA. RI Hunter, Zachary/H-3018-2013 OI Hunter, Zachary/0000-0002-1689-1691 NR 0 TC 2 Z9 2 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 NOV 16 PY 2006 VL 108 IS 11 MA 2490 BP 705A EP 705A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440003280 ER PT J AU Leleu, X Jia, XY Moreau, AS Hatjiharisi, E Ngo, H O'Sullivan, G Moreno, D Kiziltepe, T Ocio, E Ho, A Facon, T Treon, S Hideshima, T Anderson, K Ghobrial, I AF Leleu, Xavier Jia, Xiaoying Moreau, Anne-Sophie Hatjiharisi, Evdoxia Ngo, Hai O'Sullivan, Garrett Moreno, Daisy Kiziltepe, Tanyel Ocio, Enrique Ho, Allen Facon, Thierry Treon, Steven Hideshima, Teru Anderson, Kenneth Ghobrial, Irene TI Perifosine, an oral bioactive novel Akt inhibitor, induces in vitro and in vivo antitumor activity in Waldenstrom macroglobulinemia. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. CHRU, Serv Maladies Sang & Lab Immunol, Lille, France. RI FACON, THIERRY/M-9736-2014 OI FACON, THIERRY/0000-0001-7705-8460 NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 2488 BP 705A EP 705A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440003278 ER PT J AU Moreau, AS Jia, XY O'Sullivan, G Leleu, X Podar, K Daley, J Lalo, S Hatjiharisi, E Ngo, H Raab, M D'Halluin, JC Facon, T Hideshima, T Treon, S Anderson, K Ghobrial, I AF Moreau, Anne-Sophie Jia, Xiaoying O'Sullivan, Garrett Leleu, Xavier Podar, Klaus Daley, John Lalo, Suzan Hatjiharisi, Evdoxia Ngo, Hai Raab, Mark D'Halluin, Jean-Claude Facon, Thierry Hideshima, Tern Treon, Steven Anderson, Kenneth Ghobrial, Irene TI The selective protein kinase CB inhibitor, enzastaurin, induces in vitro and in vivo antitumor activity in Waldenstrom's macroglobulinemia. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. CHRU, INSERM, U817, Serv Maladies Sang, Lille, France. RI FACON, THIERRY/M-9736-2014 OI FACON, THIERRY/0000-0001-7705-8460 NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2006 VL 108 IS 11 MA 2496 BP 707A EP 707A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440003286 ER PT J AU Leleu, X O'Sullivan, G Jia, X Moreau, AS Ngo, H Hatjiharisi, E Yasui, H Hunter, Z Tai, YT Runnels, J Treon, S Hideshima, T Anderson, K Ghobrial, I AF Leleu, Xavier O'Sullivan, Garrett Jia, Xiaoying Moreau, Anne-Sophie Ngo, Hai Hatjiharisi, Evdoxia Yasui, Hiroshi Hunter, Zachary Tai, Yu-Tsu Runnels, Judith Treon, Steven Hideshima, Teru Anderson, Kenneth Ghobrial, Irene TI Novel agent perifosine enhances antitumor activity of bortezomib, rituximab and other conventional therapies in Waldenstrom's Macroglobulinemia. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. CHRU, Serv Malad Sang, Lille, France. Immunol Lab, Lille, France. RI Hunter, Zachary/H-3018-2013 OI Hunter, Zachary/0000-0002-1689-1691 NR 0 TC 1 Z9 1 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 NOV 16 PY 2006 VL 108 IS 11 MA 2517 BP 712A EP 713A PN 1 PG 2 WC Hematology SC Hematology GA 111GS UT WOS:000242440003307 ER PT J AU Krivtsov, AV Stubbs, MC Wright, R Feng, ZH Kung, AL Armstrong, SA AF Krivtsov, Andrei V. Stubbs, Matthew C. Wright, Renee Feng, Zhaohui Kung, Andrew L. Armstrong, Scott A. TI MLL-AF9 initiates leukemia from a single committed hematopoietic progenitor. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 2534 BP 717A EP 717A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440003324 ER PT J AU Kimbrel, EA Rebel, VI Kung, AL AF Kimbrel, Erin A. Rebel, Vivienne I. Kung, Andrew L. TI Comprehensive in vivo analysis of p300 hematopoietic tumor suppressor functions. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Harvard Med Sch, Dana Farber Canc Inst, Boston, MA USA. Univ Texas, Hlth Sci Ctr, Childrens Canc Res Inst, San Antonio, TX 78285 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 2553 BP 722A EP 722A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440003343 ER PT J AU Ocio, EM Hideshima, T Yasui, H Tanyel, K Ikeda, H Okawa, Y Vallet, S Jin, J Ishitsuka, K Raje, N Catley, L Anderson, KC AF Ocio, Enrique M. Hideshima, Teru Yasui, Hiroshi Tanyel, Kiziltepe Ikeda, Hirose Okawa, Yutaka Vallet, Sonia Jin, Janice Ishitsuka, Kenji Raje, Noopur Catley, Laurence Anderson, Kenneth C. TI Serotonin receptor antagonist have an in vitro and in vivo anti-myeloma effect that is mainly mediated by caspase dependent apoptosis. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Harvard Med Sch, Jerome Lipper Multiple Myeloma Ctr, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. RI Catley, Laurence/E-5313-2013 NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 2597 BP 733A EP 734A PN 1 PG 2 WC Hematology SC Hematology GA 111GS UT WOS:000242440003387 ER PT J AU Bradner, JE Shen, JP Perlstein, EO Divakaran, S Greenberg, EF Amaravadi, R Schreiber, SL AF Bradner, James E. Shen, John P. Perlstein, Ethan O. Divakaran, Sanjay Greenberg, Edward F. Amaravadi, Ravi Schreiber, Stuart L. TI Discovery and characterization of small molecule inhibitors of autophagy for cancer therapy. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 MIT, Broad Inst Harvard, Cambridge, MA USA. Dana Farber Canc Inst, Div Hematol Neoplasia, Boston, MA USA. Univ Penn, Dept Canc Biol & Med, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 2606 BP 736A EP 736A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440003396 ER PT J AU Galili, N Ebert, BL Westervelt, P Wasserman, J Lee, D Raza, FZ Golub, TR Raza, A AF Galili, Naomi Ebert, Benjamin L. Westervelt, Peter Wasserman, Jessica Lee, Daniel Raza, Fatima Z. Golub, Todd R. Raza, Azra TI Expression of proliferation related genes in myelodysplastic syndromes (MDS) and secondary acute myeloid leukemia (AML) patients with resistance to low dose vidaza and thalidomide. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Univ Massachusetts, Radhey Khanna MDS Ctr, Worcester, MA 01605 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 2658 BP 751A EP 751A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440003448 ER PT J AU Ebert, BL Galili, N Tamayo, P Mak, R Pretz, J Ladd-Acosta, C Stone, R Golub, TR Raza, A AF Ebert, Benjamin L. Galili, Naomi Tamayo, Pablo Mak, Raymond Pretz, Jennifer Ladd-Acosta, Christine Stone, Richard Golub, Todd R. Raza, Azra TI An erythroid differentiation gene expression signature predicts response to lenalidomide in myelodysplasia. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Broad Inst Harvard & MIT, Cambridge, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Univ Massachusetts, Sch Med, MDS Ctr, Worcester, MA USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 2668 BP 754A EP 754A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440003458 ER PT J AU Kawamata, N Gawa, S Levine, RL Pikman, Y Nanya, T Sanada, M Miller, CW Gary Gilliland, D Phillip Koeffler, H AF Kawamata, Norihiko Gawa, Seishi Levine, Ross L. Pikman, Yana Nanya, Toshiki Sanada, Masashi Miller, Carl W. Gary Gilliland, D. Phillip Koeffler, H. TI Genetic profiling of myeloproliferative disorders by single nucleotide polymorphism oligonucleotide microarray. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Univ Tokyo, Tokyo, Japan. Dana Farber Canc Inst, Harvard Med Sch, Boston, MA 02115 USA. Brigham & Womens Hosp, Harvard Med Sch, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 2688 BP 760A EP 760A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440003478 ER PT J AU Friedberg, JW Kelly, J Kutok, JL Salloum, R Fisher, DC Ronan, E Dalton, V Rich, L Marquis, D Rothberg, PG Liesveld, J Fisher, RI Coffman, R Mosmann, T Freedman, AS AF Friedberg, Jonathan W. Kelly, Jennifer Kutok, Jeffrey L. Salloum, Rabih Fisher, David C. Ronan, Elizabeth Dalton, Virginia Rich, Lynn Marquis, Diana Rothberg, Paul G. Liesveld, Jane Fisher, Richard I. Coffman, Robert Mosmann, Tim Freedman, Arnold S. TI Combination immunotherapy with a CpG oligonucleotide and rituximab (R) augments the immunological response and favorably alters the malignant microenvironment of follicular lymphoma (FL). SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Univ Rochester, James P Wilmot Canc Ctr, Rochester, NY USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Dynavax Technol, Berkeley, CA USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 2713 BP 767A EP 767A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440003502 ER PT J AU Damon, LE Johnson, J Niedzwiecki, D Cheson, BD Hurd, DD Bartlett, NL Byrd, JC Kelly, M Linker, C Canellos, GP AF Damon, Lloyd E. Johnson, Jeff Niedzwiecki, Donna Cheson, Bruce D. Hurd, David Duane Bartlett, Nancy L. Byrd, John C. Kelly, Michael Linker, Charles Canellos, George P. TI Immuno-chemotherapy (IC) and autologous stem cell transplant (ASCT) for untreated patients (pts) with mantle cell lymphoma (MCL): CALGB 59909. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Univ Calif San Francisco, Dept Med, San Francisco, CA USA. Duke Univ, CALGB Stat Ctr, Durham, NC USA. Georgetown Univ Hosp, Lombardi Canc Ctr, Washington, DC 20007 USA. Wake Forest Univ, Winston Salem, NC 27109 USA. Washington Univ, Sch Med, St Louis, MO USA. Ohio State Univ, Columbus, OH 43210 USA. Univ Chicago, Chicago, IL 60637 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 4 Z9 4 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 NOV 16 PY 2006 VL 108 IS 11 MA 2737 BP 774A EP 774A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440003526 ER PT J AU Freedman, AS Hamlin, PA Neelapu, S Nichols, C Robertson, M Bergier, G Winter, JN Polikoff, J Lin, T Pohlman, B Esquibel, V Melink, T Bender, J AF Freedman, Arnold S. Hamlin, Paul A. Neelapu, Sattva Nichols, Craig Robertson, Michael Bergier, Gregoire Winter, Jane N. Polikoff, Jonathan Lin, Thomas Pohlman, Brad Esquibel, Vanessa Melink, Teresa Bender, John TI Phase III trial of active immunotherapy (FavId (R), Id/KLH) following rituximab induction therapy: Clinical responses in patients (pts) with follicular non-Hodgkin's lymphoma (fNHL). SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. MD Anderson Canc Ctr, Houston, TX USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. Indiana Univ, Indianapolis, IN 46204 USA. H Lee Moffitt Canc Ctr, Tampa, FL USA. Northwestern Univ, Chicago, IL 60611 USA. Kaiser Fdn Hosp, San Diego, CA USA. Ohio State Univ, Columbus, OH 43210 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Favrille Inc, San Diego, CA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2006 VL 108 IS 11 MA 2756 BP 780A EP 780A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440003545 ER PT J AU Treon, SP Soumerai, JD Patterson, CJ Hunter, ZR Ghobrial, IM Villarreal, R Willen, MA Myers, TJ AF Treon, Steven P. Soumerai, Jacob D. Patterson, Christopher J. Hunter, Zachary R. Ghobrial, Irene M. Villarreal, Rose Willen, Michael A. Myers, Thomas J. TI Bortezomib, dexamethasone and rituximab (BDR) is a highly active regimen in the primary therapy of Waldenstrom's macroglobulinemia: Planned interim results of WMCTG clinical trial 05-180. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Dana Farber Canc Inst, Bin Ctr Waldenstroms Macroglobulinemia, Harvard Med Sch, Boston, MA 02115 USA. New York Oncol Hematol, Lantham, NY USA. Millennium Pharmaceut Inc, Cambridge, MA USA. RI Hunter, Zachary/H-3018-2013 OI Hunter, Zachary/0000-0002-1689-1691 NR 0 TC 7 Z9 8 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 NOV 16 PY 2006 VL 108 IS 11 MA 2765 BP 783A EP 783A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440003554 ER PT J AU Tsimberidou, AM Wierda, WG O'Brien, S Plunkett, WW Kipps, TJ Brown, JR Lerner, S Kantarjian, H Keating, MJ AF Tsimberidou, Apostolia-Maria Wierda, William G. O'Brien, Susan Plunkett, William W. Kipps, Thomas J. Brown, Jennifer R. Lerner, Susan Kantarjian, Hagop Keating, Michael J. TI Combination of oxaliplatin, fludarabine, cytarabine, and rituximab, in Richter's syndrome and fludarabine-refractory chronic lymphocytic leukemia. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Calif San Diego, Moores Canc Ctr, San Diego, CA 92103 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 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 NOV 16 PY 2006 VL 108 IS 11 MA 2825 BP 799A EP 799A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440003614 ER PT J AU Wierda, WG Kipps, TJ Keating, MJ Brown, JR Gribben, JG Browning, ML Rassenti, L Greaves, A Neuberg, D O'Brien, SM AF Wierda, William G. Kipps, Thomas J. Keating, Michael J. Brown, Jennifer R. Gribben, John G. Browning, M. L. Rassenti, L. Greaves, A. Neuberg, Donna O'Brien, Susan M. TI Self-administered, subcutaneous (SQ) alemtuzumab to eliminate residual disease in patients (pts) with CLL. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Calif San Diego, San Diego, CA 92103 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. St Bartholomews Hosp, London, England. CLL Res Consortium, San Diego, CA USA. NR 0 TC 2 Z9 2 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 NOV 16 PY 2006 VL 108 IS 11 MA 2839 BP 804A EP 804A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440003628 ER PT J AU Levy, O Suter, EE Kalish, LA Russell, J Scannon, P Guinan, EC AF Levy, Ofer Suter, Eugenie E. Kalish, Leslie A. Russell, Janice Scannon, Patrick Guinan, Eva C. TI Potential therapeutic intervention suggested by profound deficiency of neutrophil-derived bactericidal/permeability-increasing protein (BPI) and other alterations in LPS-directed innate immunity after myeloablative hematopoietic stem cell transplantation (HSCT). SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Childrens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. XOMA US LLC, Berkeley, CA USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 2856 BP 809A EP 809A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440003645 ER PT J AU Marty, FM Ho, VT Seeley, WW Cutler, CS Koreth, J Alyea, EP Soiffer, RJ Antin, JH Baden, LR AF Marty, Francisco M. Ho, Vincent T. Seeley, William W. Cutler, Corey S. Koreth, John Alyea, Edwin P. Soiffer, Robert J. Antin, Joseph H. Baden, Lindsey R. TI Risk of HHV6-associated post-transplant acute limbic encephalitis (PALE) after umbilical cord blood stem cell transplantation: A cohort analysis. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Brigham & Womens Hosp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA USA. Harvard Med Sch, Boston, MA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2006 VL 108 IS 11 MA 2929 BP 829A EP 829A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440003717 ER PT J AU Saito, AM Cutler, C Zahrieh, D Ho, VT Alyea, EP Soiffer, RJ Antin, JH Lee, SJ AF Saito, Akiko M. Cutler, Corey Zahrieh, David Ho, Vincent T. Alyea, Edwin P. Soiffer, Robert J. Antin, Joseph H. Lee, Stephanie J. TI Costs of complications after allogeneic myeloablative stem cell transplantation. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Brigham & Womens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 2977 BP 844A EP 844A PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440004025 ER PT J AU Brown, JR Gribben, JG Feng, Y Neuberg, D Mauch, P Nadler, LM Freedman, AS AF Brown, Jennifer R. Gribben, John G. Feng, Yang Neuberg, Donna Mauch, Peter Nadler, Lee M. Freedman, Arnold S. TI Long-term follow-up of autologous bone marrow transplantation for follicular lymphoma in first remission: Bone marrow involvement at harvest and PCR detectable disease after ex vivo purging predict relapse. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Med Sch, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 2021 L ST NW, SUITE 900, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2006 VL 108 IS 11 MA 3041 BP 865A EP 865A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440004089 ER PT J AU Avigan, D Rosenblatt, J Vasir, B Wu, Z Bissonnette, A MacNamara, C Uhl, L Lenahan, C Miller, K Joyce, R Levine, JD Proper, J Forino, P Dombagoda, D Richardson, P Munshi, NC Kufe, D AF Avigan, David Rosenblatt, Jacalyn Vasir, Baldev Wu, Zekui Bissonnette, Adam MacNamara, Claire Uhl, Lynne Lenahan, Corrine Miller, Kenneth Joyce, Robin Levine, James D. Proper, Joanne Forino, Patricia Dombagoda, Dilani Richardson, Paul Munshi, Nikhil C. Kufe, Donald TI Vaccination with dendritic cell myeloma fusions alone or in conjunction with stem cell transplantation for patients with multiple myeloma. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Beth Israel Med Ctr, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 3080 BP 878A EP 878A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440004128 ER PT J AU Andreola, G Shaffer, J Benedict Cosimi, A Kawai, T Cotter, P Dey, BR Tolkoff-Rubin, N Preffer, FI Saidman, S Kattleman, K Sachs, DH Spitzer, TR Sykes, M AF Andreola, Giovanna Shaffer, Juanita Benedict Cosimi, A. Kawai, Tatsuo Cotter, Pete Dey, Bimalangshu R. Tolkoff-Rubin, Nina Preffer, Frederic I. Saidman, Susan Kattleman, Kristin Sachs, David H. Spitzer, Thomas R. Sykes, Megan TI Donor specific unresponsiveness develops following loss of chimerism in recipients of haploidentical combined bone marrow/kidney transplantation but not in recipients of bone marrow transplant alone. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 3103 BP 884A EP 885A PN 1 PG 2 WC Hematology SC Hematology GA 111GS UT WOS:000242440004151 ER PT J AU Ting, DT Ballen, K Spitzer, TR Haspel, RL Dorn, M Preffer, F Boussiotis, V McAfee, S Attar, E Antin, JH Soiffer, RJ Cutler, C Ho, V Dey, BR AF Ting, David T. Ballen, Karen Spitzer, Thomas R. Haspel, Richard L. Dorn, Michelle Preffer, Fred Boussiotis, Vassiliki McAfee, Steven Attar, Eyal Antin, Joseph H. Soiffer, Robert J. Cutler, Corey Ho, Vincent Dey, Bimalangshu R. TI Effects of cord blood cell subset populations in the development of the dominant cord blood unit in non-myeloablative sequential double cord blood transplantation (DCBT). SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 3148 BP 898A EP 898A PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440004196 ER PT J AU Saito, TI Sykes, M AF Saito, Toshiki I. Sykes, Megan TI NK1.1(+) cells are involved in the anti-tumor immunity induced by the rejection of donor hematopoietic cells in mixed bone marrow chimeras. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Transplantat Biol Res Ctr, Boston, MA USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 3166 BP 903A EP 904A PN 1 PG 2 WC Hematology SC Hematology GA 111GS UT WOS:000242440004214 ER PT J AU Davies, JK Gorgun, G Nadler, LM Guinan, EC AF Davies, Jeff K. Gorgun, Gullu Nadler, Lee M. Guinan, Eva C. TI Effective control of mismatched alloreactivity via ex vivo alloantigen-specific co-stimulatory blockade does not significantly impact pathogen-specific immunity. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Dept Pediat, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 3177 BP 907A EP 907A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440004225 ER PT J AU Yoshida, S Ishikawa, F Shultz, LD Saito, N Fukata, M Shimoda, K Akashi, K Harada, M AF Yoshida, Shuro Ishikawa, Fumihiko Shultz, Leonard D. Saito, Noriyuki Fukata, Mitsuhiro Shimoda, Kazuya Akashi, Koichi Harada, Mine TI Expression of CD10 and CD7 defines distinct in vivo lymphoid reconstituting capacity within human cord blood CD34+CD38-cells. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 RIKEN, Ctr Allergy & Immunol, Res Unit Human Dis Model, Yokohama, Kanagawa, Japan. Kyushu Univ, Dept Med & Biosystem Sci, Fukuoka 812, Japan. Jackson Lab, Bar Harbor, ME 04609 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Kyushu Univ Hosp, Ctr Cellular & Mol Med, Fukuoka 812, Japan. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 3184 BP 909A EP 909A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440004232 ER PT J AU Rodriguez, MA Ter Veer, A Nademanee, A Niland, J Lepisto, E Kho, M LaCasce, A Weeks, JC Czuczman, M Millenson, M Friedberg, J Zelenetz, AD AF Rodriguez, Maria Alma Ter Veer, Anna Nademanee, Auayporn Niland, Joyce Lepisto, Eva Kho, Michelle LaCasce, Ann Weeks, Jane Carrie Czuczman, Myron Millenson, Michael Friedberg, Jonathan Zelenetz, Andrew D. TI Concordance with national comprehensive cancer network (NCCN) clinical practice guidelines (CPGs): A quality of care tool for newly diagnosed patients (pts) with mantle cell lymphoma (MCL). SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. City Hope Natl Med Ctr, Duarte, CA 91010 USA. Natl Comprehens Canc Network, Rockledge, PA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. James P Wilmot Canc Ctr, Rochester, NY USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 3328 BP 949A EP 950A PN 1 PG 2 WC Hematology SC Hematology GA 111GS UT WOS:000242440004376 ER PT J AU Park, JH Moore, AF Kuter, DJ AF Park, Jae H. Moore, Allan F. Kuter, David J. TI Long-term follow-up of monoclonal gammopathies in Gaucher disease patients on enzyme replacement therapy. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 3336 BP 952A EP 952A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440004384 ER PT J AU Abel, GA Sorel, MA Neufeld, EJ Weeks, JC AF Abel, Gregory A. Sorel, Marie-Adele Neufeld, Ellis J. Weeks, Jane C. TI Hematology-related direct-to-consumer advertising: A content analysis and verification of claims from print media. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Boston, MA 02115 USA. Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. RI Neufeld, Ellis/F-9331-2011 NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 3346 BP 955A EP 955A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440004394 ER PT J AU Chauhan, D Singh, A Velankar, M Hideshima, T Ovaa, H Berkers, C Bianchi, G Sitia, R Munshi, NC Richardson, P Palladino, MA Anderson, KC AF Chauhan, Dharminder Singh, Ajita Velankar, Mugdha Hideshima, Teru Ovaa, Huib Berkers, Celia Bianchi, Giada Sitia, Roberto Munshi, Nikhil C. Richardson, Paul Palladino, Michael A. Anderson, Kenneth C. TI Distinct dynamic profiles for NPI-0052-and bortezomib-induced apoptosis in multiple myeloma. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Netherlands Canc Inst, Div Cellular Biochem, NL-1066 CX Amsterdam, Netherlands. Univ Milan, Ist Sci San Raffaele, DiBiT, Milan, Italy. Nereus Pharmaceut, San Diego, CA USA. RI Berkers, Celia/I-3848-2016 NR 0 TC 3 Z9 3 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 NOV 16 PY 2006 VL 108 IS 11 MA 3396 BP 970A EP 970A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440004444 ER PT J AU Tai, YT King, B Li, C Li, XF Burger, P Song, W Shammas, M Schlossman, R Richardson, P Anderson, KC Munshi, NC AF Tai, Yu-Tzu King, Benjamin Li, Cheng Li, XianFeng Burger, Peter Song, Weihua Shammas, Masood Schlossman, Robert Richardson, Paul Anderson, Kenneth C. Munshi, Nikhil C. TI Genomic evolution of multiple myeloma in vivo over time. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. VA Healthcare Syst, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 3400 BP 971A EP 971A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440004448 ER PT J AU Hideshima, T Yasui, H Catley, L Raje, N Chauhan, D Ishitsuka, K Podar, K Mitsiades, C Tai, YT Vallet, S Kizitepe, T Ocio, E Ikeda, H Okawa, Y Hideshima, H Munshi, NC Richardson, PG Anderson, KC AF Hideshima, Teru Yasui, Hiroshi Catley, Laurence Raje, Noopur Chauhan, Dharminder Ishitsuka, Kenji Podar, Klaus Mitsiades, Constantine Tai, Yu-Tzu Vallet, Sonia Kizitepe, Tanyel Ocio, Enrique Ikeda, Hiroshi Okawa, Yutaka Hideshima, Hiromasa Munshi, Nikhil C. Richardson, Paul G. Anderson, Kenneth C. TI Akt inhibitor perifosine-induced cytotoxicity is associated with significant downregulation of survivin in human multiple myeloma (MM) cells. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Dana Farber Canc Inst Harvard Med Sch, Jerome Lipper Multiple Myeloma Ctr, Dept Med Oncol, Boston, MA USA. RI Catley, Laurence/E-5313-2013 NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 3410 BP 974A EP 974A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440004459 ER PT J AU Neri, P Tassone, P Shammas, M Fulciniti, M Tai, YT Blotta, S Prabhala, R Di Martino, M Catley, L Tagliaferri, P Venuta, S Carrasco, R Anderson, KC Munshi, NC AF Neri, Paola Tassone, Pierfirancesco Shammas, Masood Fulciniti, Mariateresa Tai, Yu-Tzu Blotta, Simona Prabhala, Rao Di Martino, Mariateresa Catley, Laurence Tagliaferri, Pierosandro Venuta, Salvatore Carrasco, Ruben Anderson, Kenneth C. Munshi, Nikhil C. TI Novel murine model to study modulation of genes and molecular pathways induced following in vivo interaction between multiple myeloma cells and human BM milieu. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA USA. VA Boston Healthcare Syst, Boston, MA USA. Univ Magna Graecia, Expt Clin Med Dept, Catanzaro, Italy. RI Catley, Laurence/E-5313-2013 NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2006 VL 108 IS 11 MA 3409 BP 974A EP 974A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440004458 ER PT J AU Podar, K Raab, MS Tonon, G Sattlerl, M Barila, D Tai, YT Yasui, H Raje, N Depinho, RA Hideshima, T Chauhan, D Anderson, KC AF Podar, Klaus Raab, Marc S. Tonon, Giovanni Sattlerl, Martin Barila, Daniela Tai, Yu-Tzu Yasui, Hiroshi Raje, Noopur Depinho, Ronald A. Hideshima, Teru Chauhan, Dharminder Anderson, Kenneth C. TI Upregulation of c-Jun induces cell death via caspase-triggered c-Abl cleavage in human multiple myeloma. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Fdn Santa Lucia, Rome, Italy. RI Barila, Daniela/K-8506-2016 OI Barila, Daniela/0000-0002-6192-1562 NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 3415 BP 975A EP 975A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440004464 ER PT J AU Okuno, Y Tatetsu, H Ueno, S Hata, H Yamada, Y Takeya, M Lino, T Akashi, K Tenen, DG Mitsuya, H AF Okuno, Yutaka Tatetsu, Hiro Ueno, Shikiko Hata, Hiroyuki Yamada, Yasuhiro Takeya, Motohiro Lino, Tadafumi Akashi, Koichi Tenen, Daniel G. Mitsuya, Hiroaki TI PU.1 is downregulated in a subset of multiple myeloma by the methylation of its-17 kb upstream regulatory region and the promoter. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Kumamoto Univ, Sch Med, Dept Hematol, Kumamoto 860, Japan. Kumamoto Univ, Sch Med, Dept Pathol 2, Kumamoto 860, Japan. Kyushu Univ Hosp, Ctr Cellular & Mol Med, Fukuoka 812, Japan. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Inst Med, Harvard Stem Cell Inst, Boston, MA USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 3417 BP 976A EP 976A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440004466 ER PT J AU Hideshima, T Bradner, JE Yasui, H Raje, N Chauhan, D Podar, K Tai, YT Mitsiades, C Richardson, PG Mazitschek, R Schreiber, SL Anderson, KC AF Hideshima, Teru Bradner, James E. Yasui, Hiroshi Raje, Noopur Chauhan, Dharminder Podar, Klaus Tai, Yu-Tzu Mitsiades, Constantine Richardson, Paul G. Mazitschek, Ralph Schreiber, Stuart L. Anderson, Kenneth C. TI Histone deacetylase-6 (HDAC6) modulates akt and STAT3 activity via heat shock protein (Hsp) 90 in human multiple myeloma SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Dana Farber Canc Inst, Harvard Med Sch, Jerome Lipper Multiple Myeloma Ctr, Dept Med Oncol, Boston, MA 02115 USA. Broad Inst Harvard, MIT, Cambridge, MA USA. Harvard Univ, Howard Hughes Med Inst, Dept Chem & Chem Biol, Cambridge, MA 02138 USA. RI Mazitschek, Ralph/E-3741-2013 OI Mazitschek, Ralph/0000-0002-1105-689X NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 3426 BP 978A EP 978A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440004475 ER PT J AU Yasui, H Hideshima, T Ikeda, H Jin, J Ocio, EM Kiziltepe, T Okawa, Y Vallet, S Chhetri, S Ishitsuka, K Tai, YT Podar, K Chauhan, D Pargellis, C Moss, N Raje, N Anderson, KC AF Yasui, Hiroshi Hideshima, Teru Ikeda, Hiroshi Jin, Janice Ocio, Enrique M. Kiziltepe, Tanyel Okawa, Yutaka Vallet, Sonia Chhetri, Shweta Ishitsuka, Kenji Tai, Yu-Tzu Podar, Klaus Chauhan, Dharminder Pargellis, Chris Moss, Neil Raje, Noopur Anderson, Kenneth C. TI BIRB796 inhibits p38 MAPK/Hsp27 pathway and enhances cytotoxicity triggered by bortezomib, Hsp90 inhibitor, and dexamethasone in multiple myeloma. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Dana Farber Canc Inst, Harvard Med Sch, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. Sapporo Med Univ, Dept Internal Med 1, Sapporo, Hokkaido, Japan. Boehringer Ingelheim Pharmaceut, Ridgefield, CT USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2006 VL 108 IS 11 MA 3440 BP 982A EP 982A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440004489 ER PT J AU Sukhdeo, K Zbeng, M Hideshima, T Anderson, KC Carrasco, DR AF Sukhdeo, Kumar Zbeng, Mei Hideshima, Tern Anderson, Kenneth C. Carrasco, Daniel R. TI beta-catenin is a novel marker of the aggresome and suggests disruption of the proteasome-aggresome-autophagasome pathway in multiple myeloma in vivo. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Dana Farber Canc Inst, Harvard Med Sch, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Dept Med Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 3449 BP 984A EP 984A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440004498 ER PT J AU Kiziltepe, T Hideshima, T Raje, N Ishitsuka, K Ocio, EM Catley, L Li, CQ Trudel, L Yasui, H Shirashi, N Tai, YT Chauhan, D Mitsiades, C Saavedra, JE Wogan, GN Keefer, LK Shami, PJ Anderson, KC AF Kiziltepe, Tanyel Hideshima, Teru Raje, Noopur Ishitsuka, Kenji Ocio, Enrique M. Catley, Laurence Li, Chun-Qi Trudel, Laura Yasui, Hiroshi Shirashi, Norihiko Tai, Yu-Tzu Chauhan, Dharminder Mitsiades, Constantine Saavedra, Joseph E. Wogan, Gerald N. Keefer, Larry K. Shami, Paul J. Anderson, Kenneth C. TI JS-K, a GST-activated nitric oxide, generator, induces DNA-double strand breaks and inhibits growth and survival of multiple myeloma cells in vitro and in vivo. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Harvard Med Sch, Jerome Lipper Multiple Myeloma Ctr, Dana Farber Canc Inst, Boston, MA USA. MIT, Biol Engn Div, Cambridge, MA 02139 USA. SAIC, Frederick, MD USA. NIH, NCI, Lab Comparat Carcinogenesis, Frederick, MD USA. Univ Utah, Salt Lake City Vet Adm Med Ctr, Div Med Oncol, Salt Lake City, UT USA. RI Catley, Laurence/E-5313-2013; Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 3453 BP 985A EP 985A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440004502 ER PT J AU Nelson, EA Hideshima, T Gashin, L Walker, SR Lynch, RA Chauhan, D Anderson, KC Frank, DA AF Nelson, Erik A. Hideshima, Teru Gashin, Laurie Walker, Sarah R. Lynch, Rebecca A. Chauhan, Dharminder Anderson, Kenneth C. Frank, David A. TI Nifuroxazide inhibits STAT3 function. and shows potent anti-tumor activity against multiple myeloma. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 3450 BP 985A EP 985A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440004499 ER PT J AU Raje, N Hideshima, T Vallet, S Chhetri, S Mitsiades, C Rooney, M Yasui, H Kiziltepe, T Podar, K Okawa, Y Ikeda, H Chauhan, D Munshi, NC Sharma, S Parikh, H Chabner, B Anderson, KC AF Raje, Noopur Hideshima, Teru Vallet, Sonia Chhetri, Shweta Mitsiades, Constantine Rooney, Melissa Yasui, Hiroshi Kiziltepe, Tanyel Podar, Klaus Okawa, Yutaka Ikeda, Hiroshi Chauhan, Dharminder Munshi, Nikhil C. Sharma, Somesh Parikh, Himanshu Chabner, Bruce Anderson, Kenneth C. TI Targeting cyclin D1 in the treatment of multiple myelloma: Preclinical validation ofa novel specific small molecule cyclin D1 inhibitor, P276-00. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Jerome Lipper Multiple Myeloma Ctr, Dana Farber Canc Inst, Boston, MA USA. Massachusetts Gen Hosp, MGH Canc Ctr, Boston, MA 02114 USA. Nicholas Piramal India Ltd, Bombay, Maharashtra, India. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2006 VL 108 IS 11 MA 3454 BP 985A EP 986A PN 1 PG 2 WC Hematology SC Hematology GA 111GS UT WOS:000242440004503 ER PT J AU Tai, YT Xu, JC Li, XF Breitkreutz, I Podar, K Hideshima, T Schlossman, R Richardson, P Munshi, NC Anderson, KC AF Tai, Yu-Tzu Xu, Jiangchun Li, Xian-Feng Breitkreutz, Iris Podar, Klaus Hideshima, Teru Schlossman, Robert Richardson, Paul Munshi, Nikhil C. Anderson, Kenneth C. TI The BAFF inhibitor AMG523 blocks adhesion and survival of human multiple myeloma cells in the bone marrow microenvironment: Clinical implication. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Med Sch, Boston, MA USA. Amgen Washington, Seattle, WA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2006 VL 108 IS 11 MA 3452 BP 985A EP 985A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440004501 ER PT J AU Neri, P Tassone, P Shammas, M Yasui, H Schipani, E Batchu, RB Blotta, S Prabhala, R Catley, L Hamasaki, M Hideshima, T Chauhan, D Jacob, GS Picker, D Venuta, S Anderson, KC Munshi, NC AF Neri, Paola Tassone, Pierfrancesco Shammas, Masood Yasui, Hiroshi Schipani, Ernestina Batchu, Ramesh B. Blotta, Simona Prabhala, Rao Catley, Laurence Hamasaki, Makoto Hideshima, Teru Chauhan, Dharminder Jacob, Gary S. Picker, Donald Venuta, Salvatore Anderson, Kenneth C. Munshi, Nilchil C. TI Biological pathways and in vivo anti-tumor activity induced by atiprimod in multiple myeloma (MM). SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 VA Boston Healthcare Syst, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Magna Graecia, Expt & Clin Med Dept, Catanzaro, Italy. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Callisto Pharmaceut, New York, NY USA. RI Catley, Laurence/E-5313-2013 NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 3455 BP 986A EP 986A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440004504 ER PT J AU Tai, YT Li, XF Breitkreutz, I Song, W Burger, P Rumizen, M Hideshima, T Podar, K Ghobrial, I Schlossman, R Richardson, P Munshi, NC Anderson, KC AF Tai, Yu-Tzu Li, Xian-Feng Breitkreutz, Iris Song, Weihua Burger, Peter Rumizen, Matthew Hideshima, Teru Podar, Klaus Ghobrial, Irene Schlossman, Robert Richardson, Paul Munshi, Nikhil C. Anderson, Kenneth C. TI Inhibition of ERK1/2 activity by the MEK1/2 inhibitor AZD6244 (ARRY-142886) induces human multiple myeloma cell apoptosis in the bone marrow microenvironment: A new therapeutic strategy for MM. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2006 VL 108 IS 11 MA 3460 BP 987A EP 987A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440004509 ER PT J AU Tai, YT Tonon, G Li, XF Rumizen, M Song, WH Morrison, A Burger, P Munshi, NC Anderson, KC AF Tai, Yu-Tzu Tonon, Giovanni Li, Xian-Feng Rumizen, Matthew Song, Weihua Morrison, Aileen Burger, Peter Munshi, Nikhil C. Anderson, Kenneth C. TI The MEK1/2 inhibitor AZD6244 (ARRY-142886) downregulates constitutive and adhesion-induced c-MAF oncogene expression and its downstream targets in human multiple myeloma. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 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 NOV 16 PY 2006 VL 108 IS 11 MA 3463 BP 988A EP 988A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440004512 ER PT J AU Breitkreutz, I Vallet, S Raab, MS Li, XF Raje, N Hideshima, T Chauhan, D Munshi, N Anderson, KC Tai, YT AF Breitkreutz, Iris Vallet, Sonia Raab, Marc S. Li, Xianfeng Raje, Noopur Hideshima, Teru Chauhan, Dharminder Munshi, Nikhil Anderson, Kenneth C. Tai, Yu-Tzu TI AZD6244 (ARRY-142886), a potent and selective MEK1/2 inhibitor blocks the ERK1/2 signaling pathway, inhibits osteoclast differentiation and activation in multiple myeloma: Clinical implications. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Jerome Lipper Multiple Myeloma Ctr, Dana Farber Canc Inst, Boston, MA USA. NR 0 TC 1 Z9 2 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 NOV 16 PY 2006 VL 108 IS 11 MA 3467 BP 989A EP 989A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440004516 ER PT J AU Negri, JM McMillin, DW Mitsiades, N Hideshima, T Chauhan, D Tai, YT Leleu, X Munshi, NC Richardson, PG Buser-Doepner, CA Pollard, J Anderson, KC Mitsiades, CS AF Negri, Joseph M. McMillin, Douglas W. Mitsiades, Nicholas Hideshima, Teru Chauhan, Dharminder Tai, Yu-Tzu Leleu, Xavier Munshi, Nikhil C. Richardson, Paul G. Buser-Doepner, Carolyn A. Pollard, John Anderson, Kenneth C. Mitsiades, Constantine S. TI Anti-myeloma activity of the small-molecule Aurora kinase inhibitor VE465. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Jerome Lipper Multiple Myeloma Ctr, Harvard Med Sch, Dana Farber Canc Inst, Dept Med, Boston, MA USA. Merck & Co Res Labs, West Point, PA USA. Vertex Pharmaceut Ltd, Oxford, England. NR 0 TC 1 Z9 1 U1 1 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2006 VL 108 IS 11 MA 3468 BP 989A EP 989A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440004517 ER PT J AU Raab, MS Podar, K Zhang, J McMillin, D Breitkreutz, I Tai, YT Lin, B Ghobrial, I Munshi, N Hideshima, T Chauhan, D Anderson, KC AF Raab, Marc S. Podar, Klaus Zhang, Jing McMillin, Douglas Breitkreutz, Iris Tai, Yu-Tzu Lin, Boris Ghobrial, Irene Munshi, Nikhil Hideshima, Teru Chauhan, Dharminder Anderson, Kenneth C. TI Targeting PKC in multiple myeloma: In vitro and in vivo effects of the novel, orally available small-molecule inhibitor enzastaurin (LY317615.HCI). SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Jerome Lipper Multiple Myeloma Ctr, Dana Farber Canc Inst, Boston, MA USA. Eli Lilly & Co, Indianapolis, IN 46285 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 3466 BP 989A EP 989A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440004515 ER PT J AU Tai, YT Song, WH Li, XF Burger, P Schlossman, R Rice, A van Abbema, A Richardson, P Munshi, NC Afar, D Anderson, KC AF Tai, Yu-Tzu Song, Weihua Li, Xian-Feng Burger, Peter Schlossman, Robert Rice, Audie van Abbema, Anne Richardson, Paul Munshi, Nikhil C. Afar, Daniel Anderson, Kenneth C. TI Killing of drug-sensitive and resistant myeloma cells and disruption of their bone marrow stromal interaction by HuLuc63, a novel humanized anti-CS1 monoclonal antibody. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Jerome Lipper Multiple Myeloma Ctr, Dana Farber Canc Inst, Boston, MA USA. PDL Biopharma Inc, Fremont, CA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2006 VL 108 IS 11 MA 3470 BP 990A EP 990A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440004519 ER PT J AU Chauhan, D Brahmandam, M Hideshima, T Podar, K Munshi, N Raje, N Anderson, KC AF Chauhan, Dharminder Brahmandam, Mohan Hideshima, Teru Podar, Klaus Munshi, Nikhil Raje, Noopur Anderson, Kenneth C. TI Bcl-2, Mcl-1 and p53 expression confer sensitivity to Bcl-2 inhibitor ABT-737 in multiple myeloma. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 3474 BP 991A EP 991A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440004523 ER PT J AU McMillin, DW Geer, DC Negri, JM Mitsiades, N Hideshima, T Chauhan, D Tai, YT Munshi, NC Richardson, PG Anderson, KC Mitsiades, CS AF McMillin, Douglas W. Geer, D. Corey Negri, Joseph M. Mitsiades, Nicholas Hideshima, Teru Chauhan, Dharminder Tai, Yu-Tzu Munshi, Nikhil C. Richardson, Paul G. Anderson, Kenneth C. Mitsiades, Constantine S. TI Reversine: A chemical probe providing insight into myeloma biology and potential therapeutic applications. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Jerome Lipper Multiple Myeloma Ctr, Harvard Med Sch, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. Jerome Lipper Multiple Myeloma Ctr, Harvard Med Sch, Dana Farber Canc Inst, Dept Med, Boston, MA USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 3481 BP 992A EP 993A PN 1 PG 2 WC Hematology SC Hematology GA 111GS UT WOS:000242440004530 ER PT J AU Breitkreutz, I Vallet, S Raab, MS Tai, YT Raje, N Hideshima, T Chauhan, D Munshi, NC Richardson, P Anderson, KC AF Breitkreutz, Iris Vallet, Sonia Raab, Marc S. Tai, Yu-Tzu Raje, Noopur Hideshima, Teru Chauhan, Dharminder Munshi, Nikhil C. Richardson, Paul Anderson, Kenneth C. TI Lenalidomide and bortezomib inhibit osteoclast differentiation and activation in multiple myeloma: Clinical implications. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 4 Z9 5 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 NOV 16 PY 2006 VL 108 IS 11 MA 3485 BP 993A EP 994A PN 1 PG 2 WC Hematology SC Hematology GA 111GS UT WOS:000242440004534 ER PT J AU O'Sullivan, G Leleu, X Jia, XY Hatjiharisi, E Ngo, H Moreau, AS Tai, YT McMillin, D Mitsiades, C Raje, N Hideshima, T Schlossman, R Richardson, P Munshi, N Anderson, K Ghobrial, I AF O'Sullivan, Garrett Leleu, Xavier Jia, Xiaoying Hatjiharisi, Evdoxia Ngo, Hai Moreau, Anne-Sophie Tai, Yu-Tsu McMillin, Douglas Mitsiades, Constantine Raje, Noopur Hideshima, Teru Schlossman, Robert Richardson, Paul Munshi, Nikhil Anderson, Kenneth Ghobrial, Irene TI The combination of the mTOR inhibitor rapamycin and proteasome inhibitor bortezomib is synergistic in vitro in multiple myeloma. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. CHRU, Immunol Lab, Serv Maladies Sang, Lille, France. NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2006 VL 108 IS 11 MA 3495 BP 996A EP 997A PN 1 PG 2 WC Hematology SC Hematology GA 111GS UT WOS:000242440004544 ER PT J AU Vallet, S Raje, N Ishitsuka, K Hideshima, T Podar, K Kizeltepe, T Yasui, H Chhetri, S Ocio, EM Jin, J Okawa, Y Ikeda, H Boccadoro, M Anderson, KC AF Vallet, Sonia Raje, Noopur Ishitsuka, Kenji Hideshima, Teru Podar, Klaus Kizeltepe, Tanyel Yasui, Hiroshi Chhetri, Shweta Ocio, Enrique M. Jin, Janice Okawa, Yutaka Ikeda, Hiroshi Boccadoro, Mario Anderson, Kenneth C. TI CCR1 inhibition impairs osteoclast activity and interaction with myeloma cells. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Jerome Lipper Multiple Myeloma Ctr, Harvard Med Sch, Dana Farber Canc Inst, Boston, MA USA. Univ Turin, Dipartimento Med & Oncol Sperimentale, Turin, Italy. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 3494 BP 996A EP 996A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440004543 ER PT J AU Braunstein, MJ Carrasco, DR Kahn, D Sukhdeo, K Protopopov, A Zhang, YY Anderson, KC Batuman, O AF Braunstein, Marc J. Carrasco, Daniel R. Kahn, David Sukhdeo, Kumar Protopopov, Alexei Zhang, Yunyu Anderson, Kenneth C. Batuman, Olcay TI Clonotypic bone marrow-derived endothelial progenitor cells in multiple myeloma. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Suny Downstate Med Ctr, Div Hematol Oncol, Brooklyn, NY 11203 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 3497 BP 997A EP 997A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440004546 ER PT J AU Stewart, K Trudel, S Chang, H Anderson, KC Richardson, P Alsina, M Reece, DE Greipp, P Young, S Sable-Hunt, A Li, ZH Keats, J Van Wier, S AF Stewart, Keith Trudel, Suzanne Chang, Hong Anderson, Kenneth C. Richardson, Paul Alsina, Melissa Reece, Donna E. Greipp, Philip Young, Steven Sable-Hunt, Alicia Li, ZhiHua Keats, Jonathon Van Wier, Scott TI Diagnostic evaluation of t[4;14] in multiple myeloma. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Mayo Clin, Scottsdale, AZ USA. Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. Dana Farber Canc Inst, Boston, MA 02115 USA. H Lee Moffitt Canc Ctr, Tampa, FL USA. Mayo Clin, Rochester, MN USA. Multiple Myeloma Res Consortium, Norwalk, CT USA. RI Keats, Jonathan/B-2047-2009 NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2006 VL 108 IS 11 MA 3501 BP 998A EP 998A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440004550 ER PT J AU Neri, P Tassone, P Shen, Z Patel, N Fajardo, R Fulciniti, M Prabhala, R Shammas, M Blotta, S Hideshima, T Chauhan, D Muller, J Venuta, S Snyder, BD Goldring, SR Anderson, KC Munshi, NC AF Neri, Paola Tassone, Pierfrancesco Shen, Zhenxin Patel, Nipun Fajardo, Robert Fulciniti, Mariateresa Prabhala, Rao Shammas, Masood Blotta, Simona Hideshima, Teru Chauhan, Dharminder Muller, John Venuta, Salvatore Snyder, Brian D. Goldring, Steven R. Anderson, Kenneth C. Munshi, Nikhil C. TI Defining a murine model to study bone disease in multiple myeloma (MM). SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA 02215 USA. VA Boston Healthcare Sys, Boston, MA USA. Magna Graecia Univ Catanzaro, Expt & Clin Med Dept, Catanzaro, Italy. Beth Israel Deaconess Med Ctr, New England Baptist Bone & Joint Inst, Boston, MA USA. Children Hosp, Dept Orthoped Surg, Boston, MA USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 3518 BP 1003A EP 1003A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440004567 ER PT J AU Bianchi, G Orsi, A Cenci, S Cascio, P Chauhan, D Anderson, KC Sitia, R AF Bianchi, Giada Orsi, Andrea Cenci, Simone Cascio, Paolo Chauhan, Dharminder Anderson, Kenneth C. Sitia, Roberto TI Direct assessment of proteasomal degradation as a potential predictor of responsiveness to bortezomib in multiple myeloma. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 DiBit, San Raffaele Sci Inst, Milan, Italy. Univ Vita Salute San Raffaele, Milan, Italy. Univ Turin, Dept Vet Morphophysiol, Turin, Italy. Harvard Med Sch, Jerome Lipper Multiple Myeloma Ctr, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 3525 BP 1005A EP 1006A PN 1 PG 2 WC Hematology SC Hematology GA 111GS UT WOS:000242440004574 ER PT J AU Mitsiades, CS Benimetskaya, L Menon, K Echart, C Rouleau, C Teicher, B Palumbo, A Boccadoro, M Lacobelli, M Anderson, KC Stein, CA Richardson, PG AF Mitsiades, Constantine S. Benimetskaya, Luba Menon, Krishna Echart, Cinara Rouleau, Cecile Teicher, Beverly Palumbo, Antonio Boccadoro, Mario Lacobelli, Massimo Anderson, Kenneth C. Stein, Cy A. Richardson, Paul G. TI Defibroticle (DF), an orally bioavailable modulator of myeloma tumor microenvironment interactions: Molecular sequelae and clinical implications. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Harvard Med Sch, Jerome Lipper Multiple Myeloma Ctr, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. Albert Einstein Montefiore Canc Ctr, Bronx, NY USA. Gentium SpA, Como, Italy. Univ Turin, Div Hematol, Turin, Italy. NR 0 TC 5 Z9 5 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2006 VL 108 IS 11 MA 3523 BP 1005A EP 1005A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440004572 ER PT J AU Dispenzieri, A Zhang, LJ Fonseca, R Vesole, DH Greipp, PR AF Dispenzieri, Angela Zhang, Lijung Fonseca, Rafael Vesole, David H. Greipp, Philip R. TI Single agent bortezomib is associated with a high response rate in patients with high risk myeloma. A phase II study from the Eastern cooperative oncology group (E2A02). SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Mayo Clin, Rochester, MN USA. Dana Farber Canc Inst, Boston, MA USA. Mayo Clin, Scottsdale, AZ USA. St Vincents Comprehens Canc Ctr, New York, NY USA. NR 0 TC 7 Z9 7 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 NOV 16 PY 2006 VL 108 IS 11 MA 3527 BP 1006A EP 1006A PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440004576 ER PT J AU Niesvizky, R Richardson, PG Sonneveld, P Schuster, MW Coleman, M Irwin, D Stadtmauer, EA Facon, T Harousseau, J Boral, A Anderson, KC AF Niesvizky, Ruben Richardson, P. G. Sonneveld, P. Schuster, M. W. Coleman, M. Irwin, D. Stadtmauer, E. A. Facon, T. Harousseau, J. Boral, A. Anderson, K. C. TI Relationship between quality of response to bortezomib (btz) and clinical benefit in multiple myeloma (MM) in the APEX and SUMMIT studies. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Cornell Univ, New York Presbyterian Hosp, Weill Med Coll, New York, NY USA. Dana Farber Canc Ctr, Boston, MA USA. Erasmus MC, Rotterdam, Netherlands. Alta Bates Comprehens Canc Ctr, Berkeley, CA USA. Univ Penn, Ctr Canc, Philadelphia, PA USA. Hosp Claude Huriez, Lille, France. Hop Hotel Dieu, Nantes, France. Millennium Pharmaceut Inc, Cambridge, MD USA. RI FACON, THIERRY/M-9736-2014 OI FACON, THIERRY/0000-0001-7705-8460 NR 0 TC 7 Z9 7 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 NOV 16 PY 2006 VL 108 IS 11 MA 3529 BP 1007A EP 1007A PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440004578 ER PT J AU Wolf, JL Richardson, P Schuster, M LeBlanc, A Battleman, D Walters, I AF Wolf, Jeffrey Lee Richardson, Paul Schuster, Michael LeBlanc, Annette Battleman, David Walters, Ian TI Utility of bortezornib retreatment for patients with relapsed multiple myeloma. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Alta Bates Comprehens Canc Ctr, Berkeley, CA USA. Dana Farber Canc Inst, Boston, MA USA. New York Presbyterian Hosp, Weill Cornell Med Ctr, New York, NY USA. Millenium Pharmaceut Inc, Cambridge, MA USA. LLC, Falls Church, VA USA. NR 0 TC 5 Z9 5 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 NOV 16 PY 2006 VL 108 IS 11 MA 3532 BP 1008A EP 1008A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440004581 ER PT J AU Chanan-Khan, AA Sonneveld, P Schuster, MW Irwin, D Stadtmauer, EA Facon, T Harousseau, JL Ben-Yehuda, D Lonial, S Goldschmidt, H Reece, DE Neuwirth, RB Anderson, KC Richardson, PG AF Chanan-Khan, Asher Alban Sonneveld, Pieter Schuster, Michael W. Irwin, David Stadtmauer, Edward A. Facon, Thierry Harousseau, Jean-Luc Ben-Yehuda, Dina Lonial, Sagar Goldschmidt, Hartmut Reece, Donna E. Neuwirth, Rachel B. Anderson, Kenneth C. Richardson, Paul G. TI Analysis of varicella zoster virus reactivation among bortezomib treated patients in the APEX study. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Roswell Pk Canc Inst, Buffalo, NY USA. Univ Rotterdam Hosp, Rotterdam, Netherlands. New York Presbyterian Hosp, New York, NY USA. Alta Bates Canc Ctr, Berkeley, CA USA. Univ Penn, Ctr Canc, Philadelphia, PA 19104 USA. Hosp Claude Huriez, Lille, France. Hop Hotel Dieu, Nantes, France. Hadassah Univ Hosp, IL-91120 Jerusalem, Israel. Emory Univ, Atlanta, GA 30322 USA. Univ Heidelberg, Med Clin V, Heidelberg, Germany. Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. Millennium Pharmaceut Inc, Cambridge, MA USA. Dana Farber Canc Inst, Boston, MA USA. RI FACON, THIERRY/M-9736-2014 OI FACON, THIERRY/0000-0001-7705-8460 NR 0 TC 3 Z9 3 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 NOV 16 PY 2006 VL 108 IS 11 MA 3535 BP 1009A EP 1009A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440004584 ER PT J AU Harousseau, JL Jagannath, S Richardson, PG Sonneveld, P Schuster, MW Esseltine, DL Anderson, KC AF Harousseau, Jean-Luc Jagannath, Sundar Richardson, Paul G. Sonneveld, Pieter Schuster, Michael W. Esseltine, Dixie-Lee Anderson, Kenneth C. TI Bortezomib in combination with high-dose dexamethasone (HD dex) and erythropoietin (EPO) does not result in an increased risk of thromboembolic complications. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Hop Hotel Dieu, Nantes, 02115, France. St Vincents Comprehens Canc Ctr, New York, NY USA. Dana Farber Canc Inst, Boston, MA USA. Univ Hosp, Rotterdam, Netherlands. New York Presbyterian Hosp, New York, NY USA. Millennium Pharmaceut Inc, Boston, MA USA. NR 0 TC 5 Z9 5 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 NOV 16 PY 2006 VL 108 IS 11 MA 3543 BP 1011A EP 1011A PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440004592 ER PT J AU Palumbo, A Rus, C Rossi, D Pregno, P Ambrosini, MT Avonto, I Gay, F Cavallo, F Iacobelli, M Gaidano, G Mitsiades, C Richardson, PG Anderson, KC Boccadoro, M AF Palumbo, Antonio Rus, Cecilia Rossi, Davide Pregno, Patrizia Ambrosini, Maria Teresa Avonto, Ilaria Gay, Francesca Cavallo, Federica Iacobelli, Massimo Gaidano, Gianluca Mitsiades, Constantine Richardson, Paul G. Anderson, Kenneth C. Boccadoro, Mario TI A multi-center phase I/II study of melphalan, prednisone, thalidomide and defibrotide in avanced multiple myeloma patients. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Univ Turin, Azienda Osped San Giovanni Battista, Div Ematol, Turin, Italy. Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. NR 0 TC 4 Z9 4 U1 1 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2006 VL 108 IS 11 MA 3560 BP 1016A EP 1017A PN 1 PG 2 WC Hematology SC Hematology GA 111GS UT WOS:000242440004609 ER PT J AU Durie, BGM Richardson, P Palumbo, A Dimopoulos, MA Cavo, M Hajek, R Joshua, DE Shimizu, K Tricot, GJ Gertz, M Tosi, P Vesole, DH Hussein, MA Ludwig, H Goldschmidt, H San Miguel, JF Sonneveld, P Vincent Rajkumar, S AF Durie, Brian G. M. Richardson, Paul Palumbo, Antonio Dimopoulos, Meletios A. Cavo, Michele Hajek, Roman Joshua, Douglas E. Shimizu, Kazuyuki Tricot, Guido J. Gertz, Morie Tosi, Patrizia Vesole, David H. Hussein, Mohamad A. Ludwig, Heinz Goldschmidt, Hartmut San Miguel, J. F. Sonneveld, Pieter Vincent Rajkumar, S. TI Deep vein thrombosis in myeloma: Estimate of prevelance and recommendations for therapy based upon a survey of members of the international myeloma working group (IMWG). SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Cedars Sinai Outpatient Canc Ctr, Aptium Oncol Inc, Los Angeles, CA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Cattedra Ematol, Turin, Italy. Alexandra Hosp, Athens, Greece. Univ Agr Brno, Brno, Czech Republic. Royal Prince Alfred Hosp, Sydney, NSW, Australia. Nagoya City Midori Gen Hosp, Nagoya, Aichi, Japan. Univ Gothenburg, Gothenburg, Sweden. Mayo Clin, Rochester, MN USA. St Vincents Comprehens Canc Ctr, New York, NY USA. Cleveland Clin, Cleveland, OH 44106 USA. Wilhelminenspital Wien, Vienna, Austria. Univ Heidelberg, Heidelberg, Germany. Univ Salamanca, E-37008 Salamanca, Spain. RI 2006, Secribsal/A-1263-2012 NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2006 VL 108 IS 11 MA 3571 BP 1020A EP 1020A PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440004620 ER PT J AU Bensinger, W Jagannath, S Becker, PS Anderson, KC Stadtmauer, EA Aukerman, L Fox, J Girish, S Bilic, S Guzy, S Solinger, A Dort, S Wang, YY Hurst, D AF Bensinger, William Jagannath, Sundar Becker, Pamela S. Anderson, Kenneth C. Stadtmauer, Edward A. Aukerman, Lea Fox, Judith Girish, Sandhva Bilic, Sanela Guzy, Serge Solinger, Alan Dort, Sherri Wang, Yongyu Hurst, Deborah TI A phase I dose escalation study of a fully human, antagonist Anti-CD40 antibody, HCD122 (formerly CHIR-12.12) in patients with relapsed and refractory multiple myeloma. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. St Vincents Comprehens Canc Ctr, New York, NY USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Penn, Philadelphia, PA 19104 USA. Novartis Oncol, Florham Pk, NJ USA. Xoma Corp, Berkeley, CA 94710 USA. NR 0 TC 8 Z9 8 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 NOV 16 PY 2006 VL 108 IS 11 MA 3575 BP 1021A EP 1021A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440004624 ER PT J AU Chanan-Khan, AA Jagannath, S Schlossman, RL Fram, RJ Falzone, RM Roberti, MF Welch, SK DePaolo, D Anderson, KC Munshi, NC AF Chanan-Khan, Asher Alban Jagannath, Sundar Schlossman, Robert L. Fram, Robert J. Falzone, Richard M. Roberti, Mary F. Welch, Samantha K. DePaolo, Dawn Anderson, Kenneth C. Munshi, Nikhil C. TI Phase I study of BB-10901 (huN901-DM1) in patients with relapsed and relapsed/refractory CD56-positive multiple myeloma. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Roswell Pk Canc Inst, Dept Med, Buffalo, NY 14263 USA. St Vincents Comprehens Canc Ctr, Multiple Myeloma Program, New York, NY USA. Dana Farber Canc Inst, Boston, MA 02115 USA. ImmunoGen Inc, Cambridge, MA USA. Boston VA Hlth Care Syst, Dept Med, Boston, MA USA. NR 0 TC 1 Z9 1 U1 3 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 NOV 16 PY 2006 VL 108 IS 11 MA 3574 BP 1021A EP 1021A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440004623 ER PT J AU Hussein, MA Berenson, JR Niesvizkyl, R Munshi, NC Matous, J Harrop, K Drachman, JG AF Hussein, Mohamad A. Berenson, James R. Niesvizkyl, Ruben Munshi, Nikhil C. Matous, Jeffrey Harrop, Kate Drachman, Jonathan G. TI Results of a phase I trial of SGN-40 (anti-huCD40 mAb) in patients with relapsed multiple myeloma. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Cleveland Clin Fdn, Cleveland, OH 44195 USA. Inst Myeloma & Bone Canc Res, W Hollywood, CA USA. Cornell Univ, Weill Med Coll, New York, NY USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Rocky Mt Canc Ctr, Denver, CO USA. Seattle Genet Inc, Bothell, WA USA. NR 0 TC 6 Z9 6 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 NOV 16 PY 2006 VL 108 IS 11 MA 3576 BP 1021A EP 1021A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440004625 ER PT J AU Siegel, D Jagannath, S Mazumder, A Vesole, D Borrello, I Sydor, J Wright, J Patterson, J Normant, E Adams, J Anderson, K Grayzel, D Richardson, P AF Siegel, David Jagannath, Sundar Mazumder, Amitabha Vesole, David Borrello, Ivan Sydor, Jens Wright, Jim Patterson, Jon Normant, Emmanuel Adams, Julian Anderson, Kenneth Grayzel, David Richardson, Paul TI Update on phase I clinical trial of IPI-504, a novel, water-soluble Hsp90 inhibitor, in patients with relapsed/refractory multiple myeloma (MM). SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Hackensack Univ, Med Ctr, Ctr Canc, Hackensack, NJ USA. St Vincents Comprehens Canc Ctr, New York, NY USA. Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Infin Pharmaceut Inc, Cambridge, MA USA. Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 3579 BP 1022A EP 1022A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440004628 ER PT J AU Siegel, DS Krishnan, A Lonial, S Chatta, G Alsina, M Jagannath, S Richardson, P Hohl, RJ Lust, JA Bensinger, W Carrum, G Moreb, J Simic, A Barlogie, B Maziarz, RT Anderson, KC Lin, J Lowe, A Vetticaden, I Zhu, J AF Siegel, David S. Krishnan, A. Lonial, S. Chatta, G. Alsina, M. Jagannath, S. Richardson, P. Hohl, R. J. Lust, J. A. Bensinger, W. Carrum, G. Moreb, J. Simic, A. Barlogie, B. Maziarz, R. T. Anderson, K. C. Lin, J. Lowe, A. Vetticaden, Is. Zhu, J. TI Phase II trial of SCIO-469 as monotherapy (M) or in combination with bortezornib (MB) in relapsed refractory multiple myeloma (MM). SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Hackensack Univ, Med Ctr, Myeloma Div, Hackensack, NJ USA. City Hope Natl Med Ctr, Duarte, CA 91010 USA. Emory Univ, Winship Canc Ctr, Atlanta, GA 30322 USA. Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. St Vincents Comprehens Canc Ctr, New York, NY USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Iowa, Iowa City, IA USA. Mayo Clin, Rochester, MN USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Baylor Univ, Texas Med Ctr, Houston, TX 77030 USA. Univ Florida, Gainesville, FL USA. Oregon Hlth & Sci Univ, Portland, OR 97201 USA. Univ Arkansas, Little Rock, AR 72204 USA. Scios Nova Inc, Fremont, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 4 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 NOV 16 PY 2006 VL 108 IS 11 MA 3580 BP 1022A EP 1022A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440004629 ER PT J AU Richardson, P Lonial, S Jakubowiak, A Wolf, J Krishnan, A Densmore, J Singhal, S Ghobrial, I Schwartzberg, L Colson, K Harris, J Kendall, T Martineau, I Obadike, N Sullivan, K Pearson, S Hideshima, T Lai, L Sportelli, P Gardner, L Birch, R Henderson, IC Anderson, KC AF Richardson, Paul Lonial, S. Jakubowiak, A. Wolf, J. Krishnan, A. Densmore, J. Singhal, S. Ghobrial, I. Schwartzberg, L. Colson, K. Harris, J. Kendall, T. Martineau, I. Obadike, N. Sullivan, K. Pearson, S. Hideshima, T. Lai, L. Sportelli, P. Gardner, L. Birch, R. Henderson, I. C. Anderson, K. C. TI A multicenter phase II study of perifosine (KRX-0401) alone and in combination with dexamethasone (Dex) for patients with relapsed or relapsed/refractory multiple myeloma (MM). SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Emory Univ, Atlanta, GA 30322 USA. Univ Michigan, Ann Arbor, MI 48109 USA. City Hope Natl Med Ctr, Duarte, CA 91010 USA. Univ Virginia, Charlottesville, VA 22903 USA. Northwestern Univ, Evanston, IL 60208 USA. NR 0 TC 5 Z9 5 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 NOV 16 PY 2006 VL 108 IS 11 MA 3582 BP 1023A EP 1023A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440004631 ER PT J AU Raje, N Woo, SB Hande, K Yap, JT Richardson, PG Vallet, S Treister, N Hideshima, T Tai, YT Chhetri, S Connell, B Szot-Barnes, A Tian, M Schlossman, RL Weeler, E Munshi, NC Van Den Abbeele, AD Anderson, KC AF Raje, Noopur Woo, Sook-Bin Hande, Karen Yap, Jeffrey T. Richardson, Paul G. Vallet, Sonia Treister, Nathaniel Hideshima, Teru Tai, Yu-Tzu Chhetri, Shweta Connell, Brendan Szot-Barnes, Agnieszka Tian, Mei Schlossman, Robert L. Weeler, Edie Munshi, Nikhil C. Van Den Abbeele, Annick D. Anderson, Kenneth C. TI Clinical, radiographic, and biomarker characterization of multiple myeloma patients with bisphosphonate associated osteonecrosis of the jaw. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Oral Med, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2006 VL 108 IS 11 MA 3591 BP 1025A EP 1026A PN 1 PG 2 WC Hematology SC Hematology GA 111GS UT WOS:000242440004640 ER PT J AU Berkofsky-Fessler, W McConnell, MJ Neuberg, DS Licht, JD AF Berkofsky-Fessler, Windy McConnell, Melanie-Jane Neuberg, Donna S. Licht, Jonathan D. TI Engineered expression of JAK2V617F drastically changes the response of progenitor cells to erythropoietin and partially mimics the polycythemia expression signature. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Mt Sinai Sch Med, Div Hematol Oncol, New York, NY USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Northwestern Univ, Feinberg Sch Med, Div Hematol Oncol, Chicago, IL 60611 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 3597 BP 1027A EP 1027A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440004646 ER PT J AU Gotlib, J George, TI Linder, A Ruddell, A Quesada, S Akin, C DeAngelo, DJ Cohen, P Graubert, T AF Gotlib, Jason George, Tracy I. Linder, Andrea Ruddell, Alisa Quesada, Sylvia Akin, Cem DeAngelo, Daniel J. Cohen, Pamela Graubert, Timothy TI Phase II trial of the tyrosine kinase inhibitor PKC412 in advanced systemic mastocytosis: Preliminary results. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Stanford Canc Ctr, Stanford, CA USA. Stanford Univ, Sch Med, Stanford, CA 94305 USA. Univ Washington, Sch Med, St Louis, MO USA. Univ Michigan, Ann Arbor, MI 48109 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2006 VL 108 IS 11 MA 3609 BP 1031A EP 1031A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440004658 ER PT J AU Sattler, M Crowley, BJ Gonneville, JR Ho, J Hudon, HH Podar, K Royer, Y Constantinescu, SN Griffin, JD AF Sattler, Martin Crowley, Brian J. Gonneville, Jeffrey R. Ho, Jeremy Hudon, Heidi H. Podar, Klaus Royer, Yohan Constantinescu, Stefan N. Griffin, James D. TI The Jak2 V617F oncogene associated with polycythemia vera requires a functional FERM domain for transformation and for expression of the myc and pim proto-oncogenes. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Ludwig Inst Canc Res, Brussels, Belgium. RI Constantinescu, Stefan /E-5277-2012 NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 3611 BP 1031A EP 1031A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440004660 ER PT J AU Gorgun, G Liu, FL Howe, E Philpot, P Guinam, E Nadler, L AF Gorgun, Gullu Liu, Fenglong Howe, Eleanor Philpot, Patrick Guinam, Eva Nadler, Lee TI Induction of alloantigen specific CD4T cell anergy by B7 : CD28 mediated costimulatory blockade significantly alters the functional program of bystander CD8, monocytes, NK and B cells. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 3656 BP 1044A EP 1044A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440004705 ER PT J AU Ho, V Dranoff, G Kim, H Pasek, M Cutler, C Alyea, E Koreth, J Antin, JH Soiffer, RJ AF Ho, Vincent Dranoff, Glenn Kim, Haesook Pasek, Mildred Cutler, Corey Alyea, Edwin Koreth, John Antin, Joseph H. Soiffer, Robert J. TI GM-CSF secreting leukemia cell vaccinations after allogeneic reduced intensity peripheral blood stem cell transplantation (SCT) for advanced myelodysplastic syndrome (MDS) or refractory acute myeloid leukemia (AML). SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 3680 BP 1052A EP 1052A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440004729 ER PT J AU Rosenblatt, J Wu, ZK Lenahan, C Vasir, B Bissonnette, A Kufe, D Avigan, D AF Rosenblatt, Jacalyn Wu, Zekui Lenahan, Corrine Vasir, Baldev Bissonnette, Adam Kufe, Donald Avigan, David TI Stimulation of anti-tumor immunity using dendritic cell/tumor fusions and anti-CD3/CD28. SO BLOOD LA English DT Meeting Abstract CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC 09-12, 2006 CL Orlando, FL SP Amer Soc Hematol C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2006 VL 108 IS 11 MA 3715 BP 1061A EP 1061A PN 1 PG 1 WC Hematology SC Hematology GA 111GS UT WOS:000242440004764 ER PT J AU Wang, JL Rao, S Chu, JL Shen, XH Levasseur, DN Theunissen, TW Orkin, SH AF Wang, Jianlong Rao, Sridhar Chu, Jianlin Shen, Xiaohua Levasseur, Dana N. Theunissen, Thorold W. Orkin, Stuart H. TI A protein interaction network for pluripotency of embryonic stem cells SO NATURE LA English DT Article ID TRANSCRIPTION FACTORS; POZ/BTB PROTEIN; MOUSE EMBRYOS; ES CELLS; NANOG; GENE; EXPRESSION; COMPLEX; DIFFERENTIATION; CULTURES AB Embryonic stem ( ES) cells are pluripotent(1,2) and of therapeutic potential in regenerative medicine(3,4). Understanding pluripotency at the molecular level should illuminate fundamental properties of stem cells and the process of cellular reprogramming. Through cell fusion the embryonic cell phenotype can be imposed on somatic cells, a process promoted by the homeodomain protein Nanog(5), which is central to the maintenance of ES cell pluripotency(6,7). Nanog is thought to function in concert with other factors such as Oct4 ( ref. 8) and Sox2 ( ref. 9) to establish ES cell identity. Here we explore the protein network in which Nanog operates in mouse ES cells. Using affinity purification of Nanog under native conditions followed by mass spectrometry, we have identified physically associated proteins. In an iterative fashion we also identified partners of several Nanog- associated proteins ( including Oct4), validated the functional relevance of selected newly identified components and constructed a protein interaction network. The network is highly enriched for nuclear factors that are individually critical for maintenance of the ES cell state and co- regulated on differentiation. The network is linked to multiple co- repressor pathways and is composed of numerous proteins whose encoding genes are putative direct transcriptional targets of its members. This tight protein network seems to function as a cellular module dedicated to pluripotency. C1 Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Harvard Stem Cell Inst, Boston, MA 02115 USA. Howard Hughes Med Inst, Boston, MA 02115 USA. RP Orkin, SH (reprint author), Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. EM stuart_orkin@dfci.harvard.edu OI Theunissen, Thorold/0000-0001-6943-7858 NR 28 TC 644 Z9 674 U1 2 U2 62 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD NOV 16 PY 2006 VL 444 IS 7117 BP 364 EP 368 DI 10.1038/nature05284 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 105GL UT WOS:000242018300048 PM 17093407 ER PT J AU Brown, RH Grant, PE Pierson, CR Harris, NL Krishnamoorthy, KS AF Brown, Robert H., Jr. Grant, P. Ellen Pierson, Christopher R. Harris, Nancy Lee Krishnamoorthy, Kalpathy S. TI A newborn boy with hypotonia - Merosin-deficient congenital muscular dystrophy. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID LAMININ ALPHA-2-CHAIN; GLYCOPROTEIN COMPLEX; EXTRACELLULAR-MATRIX; ALPHA-DYSTROGLYCAN; MUTATIONS C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Brown, RH (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. NR 15 TC 4 Z9 4 U1 0 U2 0 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 NOV 16 PY 2006 VL 355 IS 20 BP 2132 EP 2142 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 104YU UT WOS:000241997300011 PM 17108346 ER PT J AU Groeneveld, PW Matta, MA Suh, JJ Heidenreich, PA Shea, JA AF Groeneveld, Peter W. Matta, Mary Anne Suh, Janice J. Heidenreich, Paul A. Shea, Judy A. TI Costs and quality-of-life effects of implantable cardioverter-defibrillators SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Review ID SUDDEN CARDIAC DEATH; VENTRICULAR-ARRHYTHMIAS; ICD; RECIPIENTS; THERAPY; ANTIARRHYTHMICS; EXPERIENCE; ANXIETY; IMPACT; SHOCKS AB Although the clinical efficacy of implantable cardioverter-defibrillators (ICDs) has been convincingly demonstrated in clinical trials, the impact of ICDs on health care costs and recipients' quality of life (QOL) is less certain. The existing Medical research on the health care costs and QOL effects of ICDs was reviewed and summarized. Medline and the Institute for Scientific Information's.Web of Knowledge were searched for publications reporting costs of care and QOL assessments of ICD recipients. Unpublished and nonpeer-reviewed "gray" publications were excluded. Reports were included if they reported primary, original patient data that were collected after 1993, when nonthoracotomy defibrillators entered clinical practice. Two reviewers independently evaluated publications for relevance and quality, abstracted study data, and summarized the findings. Excessive heterogeneity among studies prevented formal meta-analysis, so a narrative synthesis was performed, and key themes were identified from the published research. There were limited published data on the costs of ICD care, especially for the primary prevention of sudden cardiac death. The published research on ICD QOL lacked large, multicenter, longitudinal studies. Many ICD QOL studies were performed in small numbers of patients at single centers. Initial ICD implantation costs ranged (in 2006 United States dollars) from $28,500 to $55,200, with annual follow-up costs ranging from $4,800 to $17,000. QOL was higher for ICD recipients than for patients treated with antiarrhythmic drugs, but there was a substantial prevalence of anxiety, depression, and-"loss of control" in ICD recipients, particularly in those who had received ICD shocks. In conclusion, ICD implantation remains costly but may be becoming less expensive over time, and ICD recipients' QOL is significantly affected by their devices. (c) 2006 Elsevier Inc. All rights reserved. C1 Univ Penn, Sch Med, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. VA Palo Alto Hlth Care Syst, Palo Alto, CA USA. Stanford Univ, Sch Med, Div Cardiol, Stanford, CA 94305 USA. RP Groeneveld, PW (reprint author), Univ Penn, Sch Med, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. EM peter.groeneveld@va.gov OI Heidenreich, Paul/0000-0001-7730-8490 NR 34 TC 25 Z9 25 U1 1 U2 2 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD NOV 15 PY 2006 VL 98 IS 10 BP 1409 EP 1415 DI 10.1016/j.amjcard.2006.06.041 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 133ZM UT WOS:000244052400024 PM 17134641 ER PT J AU Patel, SR Malhotra, A White, DP Gottlieb, DJ Hu, FB AF Patel, Sanjay R. Malhotra, Atul White, David P. Gottlieb, Daniel J. Hu, Frank B. TI Association between reduced sleep and weight gain in women SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE obesity; sleep deprivation; weight gain; women ID BODY-MASS INDEX; RISK-FACTOR; OBESITY; DURATION; ADULTS; REPRODUCIBILITY; QUESTIONNAIRE; DEPRIVATION; VALIDITY; DEBT AB Physiologic studies suggest that sleep restriction has metabolic effects that predispose to weight gain. The authors investigated the association between self-reported usual sleep duration and subsequent weight gain in the Nurses' Health Study. The 68,183 women who reported habitual sleep duration in 1986 were followed for 16 years. In analyses adjusted for age and body mass index, women sleeping 5 hours or less gained 1.14 kg (95% confidence interval (CI): 0.49, 1.79) more than did those sleeping 7 hours over 16 years, and women sleeping 6 hours gained 0.71 kg (95% CI: 0.41, 1.00) more. The relative risks of a 15-kg weight gain were 1.32 (95% CI: 1.19, 1.47) and 1.12 (95% CI: 1.06, 1.19) for those sleeping 5 and 6 hours, respectively. The relative risks for incident obesity (body mass index: > 30 kg/m(2)) were 1.15 (95% CI: 1.04, 1.26) and 1.06 (95% CI: 1.01, 1.11). These associations remained significant after inclusion of important covariates and were not affected by adjustment for physical activity or dietary consumption. These data suggest that short sleep duration is associated with a modest increase in future weight gain and incident obesity. Further research is needed to understand the mechanisms by which sleep duration may affect weight. C1 Case Western Reserve Univ, Div Pulm & Crit Care Med, Univ Hosp Cleveland, Cleveland, OH 44106 USA. Brigham & Womens Hosp, Dept Med, Div Sleep Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Boston Univ, Div Pulm & Crit Care Med, Boston, MA 02215 USA. VA Boston Healthcare Syst, Boston, MA USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Patel, SR (reprint author), Case Western Reserve Univ, Div Pulm & Crit Care Med, Triangle Bldg,Room 260,11400 Euclid Ave, Cleveland, OH 44106 USA. EM srp20@case.edu OI Patel, Sanjay/0000-0002-9142-5172 FU NCI NIH HHS [CA87969, P01 CA087969]; NHLBI NIH HHS [R01 HL073146, HL073146, HL081385, K08 HL081385, R01 HL073146-03]; NIA NIH HHS [AG024837, K23 AG024837, K23 AG024837-04]; NIDDK NIH HHS [DK58845, P30 DK046200, P30 DK46200, R01 DK058845] NR 27 TC 253 Z9 257 U1 1 U2 16 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD NOV 15 PY 2006 VL 164 IS 10 BP 947 EP 954 DI 10.1093/aje/kwj280 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 104LC UT WOS:000241958900004 PM 16914506 ER PT J AU Massaro, FJ Harrison, MR Soares, A AF Massaro, Frank J. Harrison, Michelle R. Soares, Adam TI Use of problem-based learning in staff training and development SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Article ID PHARMACY EDUCATION; IMPLEMENTATION C1 Tufts New England Med Ctr, Dept Pharm, Boston, MA 02111 USA. Yale New Haven Med Ctr, New Haven, CT 06504 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Massaro, FJ (reprint author), Tufts New England Med Ctr, Dept Pharm, 750 Washington St, Boston, MA 02111 USA. EM fmassaro@tufts-nemc.org NR 21 TC 2 Z9 2 U1 0 U2 2 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 USA SN 1079-2082 J9 AM J HEALTH-SYST PH JI Am. J. Health-Syst. Pharm. PD NOV 15 PY 2006 VL 63 IS 22 BP 2256 EP 2259 DI 10.2146/ajhp060120 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 114MR UT WOS:000242670800021 PM 17090747 ER PT J AU Giampietro, PF Raggio, CL Reynolds, C Ghebranious, N Burmester, JK Glurich, I Rasmussen, K McPherson, E Pauli, RM Shukla, SK Merchant, S Jacobsen, FS Faciszewski, T Blank, RD AF Giampietro, Philip F. Raggio, Cathleen L. Reynolds, Cory Ghebranious, Nader Burmester, James K. Glurich, Ingrid Rasmussen, Kristen McPherson, Elizabeth Pauli, Richard M. Shukla, Sanjay K. Merchant, Sajid Jacobsen, F. Stig Faciszewski, Thomas Blank, Robert D. TI DLL3 as a candidate gene for vertebral malformations SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE congenital scoliosis; genetics; mutation; signaling pathway ID CAUSES SPONDYLOCOSTAL DYSOSTOSIS; CONGENITAL SCOLIOSIS; NATURAL-HISTORY; DELTA HOMOLOG; MUTATIONS; SOMITOGENESIS; SEGMENTATION; ANOMALIES; DEFECTS; HUMANS AB Investigations have not identified a major locus for congenital vertebral malformations. Based on observations in mice, we hypothesized that mutations in DLL3, a member of the notch-signaling pathway, might contribute to human vertebral malformations. We sequenced the DLL3 gene in 50 patients with congenital vertebral malformations. A Caucasian male patient with VACTERL manifestations including a T5-T6 block vertebrae was heterozygous for a "G" to "A" missense mutation changing glycine to arginine at codon 269. This residue is conserved in mammals, including chimpanzee, mouse, dog, and rat. Additional testing in the patient did not show evidence of chromosome abnormalities. The patient's asymptomatic mother was also heterozygous for the missense mutation. Since this mutation was not observed in a control Population and leads to an amino acid change, it may be clinically significant. The mutation was not found in a control population of 87 anonymous individuals. Several established mechanisms could explain the mutation in both the patient and his asymptomatic mother (susceptibility allele requiring additional environmental factors, somatic mosaicism, multigenic inheritance). Documenting the absence of the mutation in a larger control population or the presence of the mutation in additional affected patients, or documenting a functional difference in DLL3 would provide further evidence supporting its causal role. (c) 2006 Wiley-Liss, Inc. C1 Marshfield Clin Fdn Med Res & Educ, Dept Med Genet Serv, Marshfield, WI 54449 USA. Hosp Special Surg, Dept Pediat Orthoped, New York, NY 10021 USA. Marshfield Clin Res Fdn, Clin Res Ctr, Marshfield, WI USA. Marshfield Clin Fdn Med Res & Educ, Mol Diagnost Lab, Marshfield, WI USA. Marshfield Clin Res Fdn, Ctr Human Genet, Marshfield, WI USA. Marshfield Clin Res Fdn, Off Res Facilitat, Marshfield, WI USA. Univ Wisconsin, Clin Genet Ctr, Madison, WI USA. Marshfield Clin Fdn Med Res & Educ, Dept Orthoped Spine Surg, Marshfield, WI USA. Univ Wisconsin, Sch Med, Madison, WI USA. William S Middleton Mem Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, Madison, WI 53705 USA. RP Giampietro, PF (reprint author), Marshfield Clin Fdn Med Res & Educ, Dept Med Genet Serv, 1000 N Oak Ave, Marshfield, WI 54449 USA. EM giampietro.philip@marshfieldclinic.org OI Blank, Robert Daniel/0000-0003-2950-1944 NR 30 TC 18 Z9 21 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 NOV 15 PY 2006 VL 140A IS 22 BP 2447 EP 2453 DI 10.1002/ajmg.a.31509 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 101MZ UT WOS:000241746200008 PM 17041936 ER PT J AU Chen, WH Shao, XB Moellering, R Wennersten, C Regen, SL AF Chen, Wen-Hua Shao, Xue-Bin Moellering, Robert Wennersten, Christine Regen, Steven L. TI A bioconjugate approach toward squalamine mimics: Insight into the mechanism of biological action SO BIOCONJUGATE CHEMISTRY LA English DT Article ID CATIONIC STEROID ANTIBIOTICS; ANTIMICROBIAL RESISTANCE; SYNTHETIC IONOPHORES; ION CHANNELS; ACID; PEPTIDE; FUTURE; SHARK; DRUG; OLIGONUCLEOTIDE AB A short and efficient synthesis has been devised for a family of squalamine mimics, based on the use of cholic acid, deoxycholic acid, lithocholic acid, putrescine, and spermine as starting materials. Those mimics that contain two facially amphiphilic sterol- spermidine conjugates show strong antibacterial activity against a broad spectrum of Gram- positive bacteria; their corresponding activities against a broad spectrum of Gram- negative bacteria are relatively moderate. Larger mimics, containing four such sterol- spermidine conjugates, exhibit very weak activities. Reversal of the pendent spermidine moiety and a putrescine linkage on the A- and D- rings had little consequence on the antibacterial activity for the most active of the squalamine mimics, which contained two sterol- polyamine units; similar results were obtained with squalamine mimics made from only one sterol unit. Detailed structure-activity measurements, in combination with kinetic studies carried out using liposomes as model membranes, support a mechanism of action involving noncovalent dimers as ion transporting species, most probably via the formation of pores or channels. C1 Lehigh Univ, Dept Chem, Bethlehem, PA 18015 USA. Harvard Univ, Inst Med, BIDMC, Boston, MA 02115 USA. RP Regen, SL (reprint author), Lehigh Univ, Dept Chem, Bethlehem, PA 18015 USA. EM slr0@lehigh.edu RI Shao, Xue-Bin/B-7477-2008 NR 31 TC 28 Z9 28 U1 3 U2 9 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD NOV 15 PY 2006 VL 17 IS 6 BP 1582 EP 1591 DI 10.1021/bc060220h PG 10 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 105HL UT WOS:000242020900028 PM 17105239 ER PT J AU Hong, FX Breitling, R McEntee, CW Wittner, BS Nemhauser, JL Chory, J AF Hong, Fangxin Breitling, Rainer McEntee, Connor W. Wittner, Ben S. Nemhauser, Jennifer L. Chory, Joanne TI RankProd: a bioconductor package for detecting differentially expressed genes in meta-analysis SO BIOINFORMATICS LA English DT Article AB While meta-analysis provides a powerful tool for analyzing microarray experiments by combining data from multiple studies, it presents unique computational challenges. The Bioconductor package RankProd provides a new and intuitive tool for this purpose in detecting differentially expressed genes under two experimental conditions. The package modifies and extends the rank product method proposed by Breitling et al., [(2004) FEBS Lett., 573, 83-92] to integrate multiple microarray studies from different laboratories and/or platforms. It offers several advantages over t-test based methods and accepts pre-processed expression datasets produced from a wide variety of platforms. The significance of the detection is assessed by a non-parametric permutation test, and the associated P-value and false discovery rate (FDR) are included in the output alongside the genes that are detected by user-defined criteria. A visualization plot is provided to view actual expression levels for each gene with estimated significance measurements. Availability: RankProd is available at Bioconductor http://www.bioconductor.org. A web-based interface will soon be available at http://cactus.salk.edu/RankProd Contact: fhong@salk.edu Supplementary information: Supplementary data are available at Bioinformatics online. C1 Salk Inst Biol Studies, Plant Biol Lab, La Jolla, CA USA. Salk Inst Biol Studies, Howard Hughes Med Inst, La Jolla, CA USA. Univ Groningen, Groningen Bioinformat Ctr, Haren, Netherlands. Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA. Univ Washington, Dept Biol, Seattle, WA 98195 USA. RP Hong, FX (reprint author), Salk Inst Biol Studies, Plant Biol Lab, La Jolla, CA USA. EM fhong@salk.edu OI Breitling, Rainer/0000-0001-7173-0922 NR 13 TC 358 Z9 362 U1 5 U2 26 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD NOV 15 PY 2006 VL 22 IS 22 BP 2825 EP 2827 DI 10.1093/bioinformatics/btl476 PG 3 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 104KT UT WOS:000241958000020 PM 16982708 ER PT J AU Tang, YL Buxbaum, SG Waldman, I Anderson, GM Zabetian, CP Kohnke, MD Cubells, JF AF Tang, YiIang Buxbaum, Sarah G. Waldman, Irwin Anderson, George M. Zabetian, Cyrus P. Koehnke, Michael D. Cubells, Joseph F. TI A single nucleotide polymorphism at DBH, possibly associated with attention-deficit/hyperactivity disorder, associates with lower plasma dopamine beta-hydroxylase activity and is in linkage disequilibrium with two putative functional single nucleotide polymorphisms SO BIOLOGICAL PSYCHIATRY LA English DT Article DE dopamine beta-hydroxylase; attention-deficit/hyperactivity disorder; linkage disequilibrium; genetic association ID DEFICIT HYPERACTIVITY DISORDER; GENE DBH; LOCUS; HAPLOTYPE; DAT1; ADHD; ALLELES; DRD5 AB Background: The DBH gene regulates plasma dopamine beta-hydroxylase activity (pD beta H). Two single nucleotide polymorphisms (SNPs), -1021C -> T (rs1611115; SNP1) and + 1603C -> T (rs6271; SNP3), independently influence pD beta H. Another SNP, commonly known as DBH Taq1A (rs2519152; SNP2) is associated with attention-deficit/hyperactivity disorder (ADHD) in some (but not all) studies. We tested whether 1) SAP2 associates with pD beta H; and 2) whether linkage disequilibrium (LD) between SNP2 and the other SNPs explains that association. Methods: Plasma dopamine beta-hydroxylase activity and genotypes at the SNPs were determined in Caucasian subjects (n = 418). Associations to pD beta H were examined using analyses of variance (ANOVAs) and LD among the SNPs using estimation maximization. Results: 1) Each polymorphism analyzed alone associated with pD beta H; 2) SNP2 was in strong LD with SNP1 and SNP3, respectively, but there was no significant LD between SNP1 and SNP3; and 3) analyzed jointly, each SNP contributed significantly and uniquely to plasma D beta H activity. Conclusions: 1) SNP2 associates with pD beta H; 2) SNP2 shows LD with SNP1 and SNP3; 3) most of the association between SNP2 and pD beta H simply reflects that LD; however, 4) SNP2 also appears to exert a small independent effect on pD beta H, suggesting that SNP2, or another variant in LD with it, uniquely influences pD beta H. C1 Yale Univ, Sch Med, Dept Psychiat, New Haven, CT USA. VA Connecticut Healthcare Syst, New Haven, CT USA. Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA USA. Emory Univ, Dept Psychol, Atlanta, GA 30322 USA. Yale Univ, Sch Med, Yale Child Study Ctr, New Haven, CT USA. Univ Washington, Sch Med, Dept Neurol, Seattle, WA USA. VA Puget Sound Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Seattle, WA USA. Univ Tubingen Hosp, Hosp Psychiat & Psychotherapy, Tubingen, Germany. RP Cubells, JF (reprint author), Emory Univ, Sch Med, Dept Human Genet, 615 Michael St,Suite 301, Atlanta, GA 30322 USA. EM jcubells@genetics.emory.edu RI Buxbaum, Sarah/E-1970-2013 OI Buxbaum, Sarah/0000-0002-4886-3564 FU NIDA NIH HHS [K02 DA 015766, R01 DA 12422]; NIMH NIH HHS [K01 MH 01818, T32 MH 2005]; NINDS NIH HHS [K08 NS 44138] NR 29 TC 27 Z9 30 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 NOV 15 PY 2006 VL 60 IS 10 BP 1034 EP 1038 DI 10.1016/j.biopsych.2006.02.017 PG 5 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 104EM UT WOS:000241939200003 PM 16616730 ER PT J AU Seidman, LJ Valera, EM Makris, N Monuteaux, MC Boriel, DL Kelkar, K Kennedy, DN Caviness, VS Bush, G Aleardi, M Faraone, SV Biederman, J AF Seidman, Larry J. Valera, Eve M. Makris, Nikos Monuteaux, Michael C. Boriel, Denise L. Kelkar, Kalika Kennedy, David N. Caviness, Verne S. Bush, George Aleardi, Meg Faraone, Stephen V. Biederman, Joseph TI Dorsolateral prefrontal and anterior cingulate cortex volumetric abnormalities in adults with attention-deficit/hyperactivity disorder identified by magnetic resonance imaging SO BIOLOGICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Academy-of-Child-and-Adolescent-Psychiatry CY OCT, 2005 CL Toronto, CANADA SP Amer Acad Child & Adolescent Psychiat DE attention-deficit/hyperactivity disorder; anterior cingulate; prefrontal cortex; structural MRI ID DEFICIT HYPERACTIVITY DISORDER; ANATOMICALLY SPECIFIED METHOD; CAUDATE-NUCLEUS; CORTICAL ABNORMALITIES; LIFE-SPAN; MRI; ADHD; PARCELLATION; BOYS; ADOLESCENTS AB Objectives: Gray and white matter volume deficits have been reported in a number of studies of children with attention-deficit/hyperactivity disorder (ADHD); however, there is a paucity of structural magnetic resonance imaging (MRI) studies of adults with ADHD. This structural MRI study used an a priori region of interest approach. Methods: Twenty-four adults with DSM-IV ADHD and 18 healthy controls comparable on age, socioeconomic status, sex, handedness, education, IQ, and achievement test performance bad an MRI on a 1.5T Siemens scanner. Cortical and sub-cortical gray and white matter were segmented. Image parcellation divided the neocortex into 48 gyral-based units per hemisphere. Based on a prior hypotheses we focused on prefrontal, anterior cingulate cortex (ACC) and overall gray matter volumes. General linear analyses of the volumes of brain regions, adjusting for age, sex, and total cerebral volumes, were used to compare groups. Results: Relative to controls, ADHD adults had significantly smaller overall cortical gray matter, prefrontal and ACC volumes. Conclusions. Adults with ADHD have volume differences in brain regions in areas involved in attention and executive control. These data, largely consistent with studies of children, support the idea that adults with ADHD have a valid disorder with persistent biological features. C1 Clin & Res Program Pediat Psychopharmacol, Boston, MA 02114 USA. Harvard Univ, Sch Med,Beth Israel Deaconess Med Ctr, Dept Psychiat,Mass Mental Hlth Ctr, Publ Psychiat Div, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Radiol Serv, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Ctr Morphometr Anal, Boston, MA 02114 USA. Harvard Univ, Sch Med, MIT, Martinos Ctr Biomed Imaging, Boston, MA USA. Massachusetts Gen Hosp, Charlestown, MA USA. SUNY Upstate Med Univ, Genet Res Program, Syracuse, NY USA. SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY USA. RP Seidman, LJ (reprint author), Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, Fruit St,Warren 7, Boston, MA 02114 USA. EM lseidman@bidmc.harvard.edu RI Kennedy, David/H-3627-2012; OI Faraone, Stephen/0000-0002-9217-3982 FU NCRR NIH HHS [P41 RR 14075]; NICHD NIH HHS [MH/HD 62152]; NIMH NIH HHS [F32 MH 065040-01A1, MH 16259, MH 57934] NR 76 TC 178 Z9 183 U1 4 U2 14 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 NOV 15 PY 2006 VL 60 IS 10 BP 1071 EP 1080 DI 10.1016/j.biopsych.2006.04.031 PG 10 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 104EM UT WOS:000241939200008 PM 16876137 ER PT J AU Faraone, SV Biederman, J Doyle, A Murray, K Petty, C Adamson, JJ Seidman, L AF Faraone, Stephen V. Biederman, Joseph Doyle, Alysa Murray, Kate Petty, Carter Adamson, Joel J. Seidman, Larry TI Neuropsychological studies of late onset and subthreshold diagnoses of adult attention-deficit/hyperactivity disorder SO BIOLOGICAL PSYCHIATRY LA English DT Article DE attention deficit disorder (ADD); attention-deficit/hyperactivity disorder (ADHD); neuropsychology; diagnosis; adult; subthreshold ID DEFICIT HYPERACTIVITY DISORDER; PSYCHIATRIC STATUS; RESEARCH CRITERIA; ADHD; CHILDREN; AGE; SYMPTOMS; PERFORMANCE; DEFINITION; IMPACT AB Background: Diagnosing attention-deficit/hyperactivity disorder (ADHD) in adults is difficult when the diagnostician cannot establish an onset prior to the DSM-IV criterion of age 7 or if the number of symptoms recalled does not achieve the DSM-IV threshold for diagnosis. Because neuropsychological deficits are associated with ADHD, we addressed the validity of the DSM-IV age at onset and symptom threshold criteria by using neuropsychological test scores as external validators. Methods: We compared four groups of adults 1) full ADHD subjects met all DSM-IV criteria for childhood-onset ADHD; 2) late-onset ADHD subjects met all criteria except The age at onset criterion; 3) subthreshold ADHD subjects did not meet full symptom criteria; and 4) non-ADHD subjects did not meet any of the above criteria. Results: Late-onset and full ADHD subjects had similar patterns of neuropsychological dysfunction. By comparison, subthreshold ADHD subjects showed few neuropsychological differences with non-ADHD subjects. Conclusions: Our results showing similar neuropsychological underpinning in subjects with late-onset ADHD suggest that the DSM-IV age at onset criterion may be too stringent. Our data also suggest that ADHD subjects who failed to ever meet the DSM-IV threshold for diagnosis have a milder form of the disorder. C1 SUNY Upstate Med Univ, Dept Psychiat & Behav Sci, Syracuse, NY 13210 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp,Yawkey Ctr Outpatient Care, Dept Psychiat,Pediat Psychopharmacol Unit, Boston, MA 02115 USA. RP Faraone, SV (reprint author), SUNY Upstate Med Univ, Dept Psychiat & Behav Sci, 750 E Adams St, Syracuse, NY 13210 USA. EM faraones@upstate.edu OI Adamson, Joel/0000-0002-1399-5786; Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [R01 MH 57934] NR 58 TC 72 Z9 73 U1 4 U2 11 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 NOV 15 PY 2006 VL 60 IS 10 BP 1081 EP 1087 DI 10.1016/j.biopsych.2006.03.060 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 104EM UT WOS:000241939200009 PM 16876139 ER PT J AU Biederman, J Monuteaux, MC Mick, E Spencer, T Wilens, TE Klein, KL Price, JE Faraone, SV AF Biederman, Joseph Monuteaux, Michael C. Mick, Eric Spencer, Thomas Wilens, Timothy E. Klein, Kristy L. Price, Julia E. Faraone, Stephen V. TI Psychonathology in female with attention-deficit/hyperactivity disorder: A controlled, five-year prospective study SO BIOLOGICAL PSYCHIATRY LA English DT Article DE ADHD; adolescence; comorbidity; females; longitudinal follow up; survival analysis ID DEFICIT HYPERACTIVITY DISORDER; FOLLOW-UP; PSYCHIATRIC STATUS; CIGARETTE-SMOKING; BIPOLAR DISORDER; CHILDREN; ADHD; GIRLS; COMORBIDITY; ADOLESCENTS AB Background: Despite the importance of understanding the long-term outcome of children with attention-deficit/hyperactivity disorder (ADHD), the available literature is predominantly based on male samples. This study estimated the lifetime burden of comorbid psychopathology in a large sample of girls with and without ADHD followed up over five years. Methods: We conducted a blind, five-year prospective longitudinal study of girls with (n = 140) and without (n = 122) ADHD, aged 6-18 years at baseline, consecutively ascenained from either community pediatricians or psychiatrists at an academic medical center. At the five-year follow-up, 123 (8896) and 112 (92%) of the ADHD and control children, respectively, were re-assessed at a mean age of 16.7 years. Psychiatric disorders were assessed using blinded structured diagnostic interviews. Results. At follow-up, females with ADHD were at significantly higher risk than controls to manffest disruptive behavior, mood and anxiety disorders, and substance dependence. The magnitude of increased risk was greatest,for major depression and oppositional defiant disorder, followed by substance dependence and anxiety disorders. Conclusions: These prospective follow-up findings documenting high morbidity associated with ADHD extend to females previously reported findings in male samples and underscore the importance of early recognition and intervention efforts for youth with ADHD of both genders. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Yawkey Ctr Outpatient Care YAW 6A 6900, Dept Psychiat, Boston, MA 02114 USA. SUNT Upstate Med Univ, Dept Psychiat & Behav Sci, Syracuse, NY USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit, Yawkey Ctr Outpatient Care YAW 6A 6900, Dept Psychiat, 32 Fruit St, Boston, MA 02114 USA. EM jbeiderman@partners.org OI Mick, Eric/0000-0001-8505-8145; Faraone, Stephen/0000-0002-9217-3982 FU NICHD NIH HHS [5R01 HD 36317-07] NR 36 TC 87 Z9 89 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 NOV 15 PY 2006 VL 60 IS 10 BP 1098 EP 1105 DI 10.1016/j.biospych.2006.02.031 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 104EM UT WOS:000241939200011 PM 16712802 ER PT J AU Biederman, J Gao, HT Rogers, AK Spencer, TJ AF Biederman, Joseph Gao, Haitao Rogers, Ann K. Spencer, Thomas J. TI Comparison of parent and teacher reports of attention-deficit/hyperactivity disorder symptoms from two placebo-controlled studies of atomoxetine in children SO BIOLOGICAL PSYCHIATRY LA English DT Article DE atomoxetine; attention-deficit/hyperactivity disorder; clinical trials; pooled analysis; long-acting treatments; parent reports ID DEFICIT HYPERACTIVITY DISORDER; ONCE-DAILY ATOMOXETINE; METHYLPHENIDATE; ADOLESCENTS; ADHD AB Background: The validity of parent reports regarding children's attention-deficit/hyperactivity disorder (ADHD) symptoms has been questioned. This study assessed weather parent reports were as sensitive as teacher reports to document change in ADHD symptoms during clinical trials with atomoxetine. Methods: Data were compared from two randomized, double-blind, placebo-controlled clinical trials of atomoxetine using different versions (parent or teacher) of the same rating scale (Attention-Deficit/Hyperactivity Disorder Rating Scale-IV [parent or teacher] Version: Investigator Administered and Scored-ADHD RS). Exclusion criteria included history of bipolar disorder, psychosis, seizures, alcohol abuse, or positive drug screen. Patients (6-16years old) were treated with atomoxetine (titrated to a maximum dose of 1.8 mg/kg/day) administered once daily for up to 7 weeks. Parent and teacher ratings were compared using an analysis of covariance (ANCOVA) model. Results: The analysis (n = 318) showed that treatment effects (mean change, baseline to endpoint) were similar between parent and teacher ratings (total, p = .762; inattention, p = .519; hyperactive/impulsive, p = .955). Effect sizes also were similar based on total scores (parent ratings =.69, teacher ratings =.63). Conclusions: Parent reports are as sensitive as teacher reports in assessing the efficacy of long-acting pharmacologic treatment for ADHD in children during clinical trials using the nonstimulant atomoxetine. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit ACC 725, Boston, MA 02114 USA. Lilly Res Labs, Indianapolis, IN USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit ACC 725, 15 Parkman St, Boston, MA 02114 USA. EM jbiederman@partners.org NR 21 TC 15 Z9 17 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 NOV 15 PY 2006 VL 60 IS 10 BP 1106 EP 1110 DI 10.1016/j.biopsych.2006.03.036 PG 5 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 104EM UT WOS:000241939200012 PM 16806096 ER PT J AU Stone, RM AF Stone, Richard M. TI Older AML patients: fit for what? SO BLOOD LA English DT Editorial Material ID ACUTE MYELOID-LEUKEMIA; FLT3; INHIBITOR C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Stone, RM (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. NR 5 TC 0 Z9 0 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 NOV 15 PY 2006 VL 108 IS 10 BP 3232 EP 3233 DI 10.1182/blood-2006-09-042960 PG 2 WC Hematology SC Hematology GA 103VM UT WOS:000241915000004 ER PT J AU Kamphuis, E Junt, T Waibler, Z Forster, R Kalinke, U AF Kamphuis, Elisabeth Junt, Tobias Waibler, Zoe Forster, Reinhold Kalinke, Ulrich TI Type I interferons directly regulate lymphocyte recirculation and cause transient blood lymphopenia SO BLOOD LA English DT Article ID CD8 T-CELLS; NECROSIS-FACTOR-ALPHA; DENDRITIC CELLS; IMMUNE-RESPONSE; CLONAL EXPANSION; IFN-ALPHA/BETA; CUTTING EDGE; STRANDED-RNA; B-CELLS; VIRUS AB Early viral infection is often associated with lymphopenia, a transient reduction of blood lymphocyte counts long before the onset of clinical symptoms. We have investigated lymphopenia in mice infected with vesicular stomatitis virus (VSV) or treated with the Toll-like receptor (TLR) agonists poly(I:C) and R-848. In all cases analyzed, lymphopenia was critically dependent on type I interferon receptor (IFNAR) signaling. With the use of bone marrow-chimeric mice, radioresistant cells, such as stroma and endothelium, could be excluded as type I interferon (IFN-alpha/p) targets for the induction of lymphopenia. Instead, adoptive transfer experiments and studies in conditionally gene-targeted mice with a B- or T-cell-specific IFNAR deletion demonstrated that IFN-alpha/beta exerted a direct effect on lymphocytes that was necessary and largely sufficient to induce lymphopenia. Furthermore, after treatment with R-848, we found that other cytokines such as TNF-alpha also played a role in T-cell lymphopenia. Investigation of the molecular mechanism revealed that lymphopenia was mainly independent of G protein-coupled receptors (GPCRs) and chemokines. In an adhesion assay, B cells of poly(I:C)-treated mice showed moderately increased adhesion to ICAM-1 but not to VCAM-1. In conclusion, our data identify a new effect of direct IFN-alpha/beta stimulation of lymphocytes that profoundly affects lymphocyte redistribution. C1 Paul Ehrlich Inst, Div Immunol, D-63225 Langen, Germany. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, CBR, Inst Biomed Res, Boston, MA 02115 USA. Hannover Med Sch, Inst Immunol, D-3000 Hannover, Germany. RP Kalinke, U (reprint author), Paul Ehrlich Inst, Div Immunol, Paul Ehrich Str 51-59, D-63225 Langen, Germany. EM kalul@pei.de RI Forster, Reinhold/D-6770-2011 NR 63 TC 103 Z9 104 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 NOV 15 PY 2006 VL 108 IS 10 BP 3253 EP 3261 DI 10.1182/blood-2006-06-027599 PG 9 WC Hematology SC Hematology GA 103VM UT WOS:000241915000011 PM 16868248 ER PT J AU Adnan, S Balamurugan, A Trocha, A Bennett, MS Ng, HL Ali, A Brander, C Yang, OO AF Adnan, Sama Balamurugan, Arumugam Trocha, Alicja Bennett, Michael S. Ng, Hwee L. Ali, Ayub Brander, Christian Yang, Otto O. TI Nef interference with HIV-1-specific CTL antiviral activity is epitope specific SO BLOOD LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; CYTOTOXIC T-LYMPHOCYTES; COMPLEX CLASS-I; LONG-TERM NONPROGRESSORS; HIV-1 NEF; DOWN-REGULATION; CELL RESPONSES; VIRAL LOAD; HLA-C; EXPRESSION KINETICS AB HIV-1 Nef and HIV-1-specific cytotoxic T lymphocytes (CTLs) have important and opposing roles in the immunopathogenesis of HIV-1 infection. Nef-mediated down-modulation of HILA class I on infected cells can confer resistance to CTL clearance, but the factors determining the efficiency of this process are unknown. This study examines the impact of Nef on the antiviral activity of several CTL clones recognizing epitopes from early and late HIV-1 proteins, restricted by HLA-A, -B, and -C molecules. CTL-targeting epitopes in early proteins remained susceptible to the effects of Nef, although possibly to a lesser degree than CTL-targeting late protein epitopes, indicating that significant Nef-mediated HILA down-regulation can precede even the presentation of early protein-derived epitopes. However, HLA-C-restricted CTLs were unaffected by Nef, consistent with down-regulation of cell-surface HLA-A and -B but not HLA-C molecules. Thus, CTLs vary dramatically in their susceptibility to Nef interference, suggesting differences in the relative importance of HLA-A- and HLA-B- versus HLA-C-restricted CTLs in vivo. The data thus indicate that HLA-C-restricted CTLs may have an under-appreciated antiviral role in the setting of Nef in vivo and suggest a benefit of promoting HLA-C-restricted CTLs for immunotherapy or vaccine development. C1 Univ Calif Los Angeles, Med Ctr, David Geffen Sch Med, Dept Med,Div Infect Dis, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA. Harvard Univ, Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02115 USA. RP Yang, OO (reprint author), Univ Calif Los Angeles, Med Ctr, David Geffen Sch Med, Dept Med,Div Infect Dis, 37-121 CHS,10833 LeConte Ave, Los Angeles, CA 90095 USA. EM oyang@mednet.ucla.edu OI Brander, Christian/0000-0002-0548-5778 FU NIAID NIH HHS [AI051970, AI067077] NR 52 TC 43 Z9 43 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 NOV 15 PY 2006 VL 108 IS 10 BP 3414 EP 3419 DI 10.1182/blood-2006-06-030668 PG 6 WC Hematology SC Hematology GA 103VM UT WOS:000241915000032 PM 16882705 ER PT J AU Chen, LF Juszczynski, P Takeyama, K Aguiar, RCT Shipp, MA AF Chen, Linfeng Juszczynski, Przemyslaw Takeyama, Kunihiko Aguiar, Ricardo C. T. Shipp, Margaret A. TI Protein tyrosine phosphatase receptor-type O truncated (PTPROt) regulates SYK phosphorylation, proximal B-cell-receptor signaling, and cellular proliferation SO BLOOD LA English DT Article ID ACUTE LYMPHOBLASTIC-LEUKEMIA; TUMOR-SUPPRESSOR GENE; ANTIGEN-RECEPTOR; MOLECULAR-CLONING; KINASE; EXPRESSION; IDENTIFICATION; MACROPHAGES; BCR; LOCALIZATION AB The strength and duration of B-cell-receptor (BCR) signaling depends upon the balance between protein tyrosine kinase (PTK) activation and protein tyrosine phosphatase (PTP) inhibition. BCR-dependent activation of the SYK PTK initiates downstream signaling events and amplifies the original BCR signal. Although BCR-associated SYK phosphorylation is clearly regulated by PTPs, SYK has not been identified as a direct PTP substrate. Herein, we demonstrate that SYK is a major substrate of a tissue-specific and developmentally regulated PTP, PTP receptor-type 0 truncated (PTPROt). PTPROt is a member of the PTPRO family (also designated GLEPP, PTP-O, PTP-oc, and PTPu2), a group of highly conserved receptor-type PTPs that are thought to function as tumor suppressor genes. The overexpression of PTPROt inhibited BCR-triggered SYK tyrosyl phosphorylation, activation of the associated adaptor proteins SHC and BLNK, and downstream signaling events, including calcium mobilization and mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) activation. PTPROt overexpression also inhibited lymphoma cell proliferation and induced apoptosis in the absence of BCR cross-linking, suggesting that the phosphatase modulates tonic BCR signaling. C1 Dana Farber Canc Inst, Div Hematol Malignancies, Boston, MA 02115 USA. RP Shipp, MA (reprint author), Dana Farber Canc Inst, Div Hematol Malignancies, 44 Binney St, Boston, MA 02115 USA. EM margaret_shipp@dfci.harvard.edu NR 40 TC 56 Z9 56 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 NOV 15 PY 2006 VL 108 IS 10 BP 3428 EP 3433 DI 10.1182/blood-2006-03-013821 PG 6 WC Hematology SC Hematology GA 103VM UT WOS:000241915000034 PM 16888096 ER PT J AU Catley, L Weisberg, E Kiziltepe, T Tai, YT Hideshima, T Neri, P Tassone, P Atadja, P Chauhan, D Munshi, NC Anderson, KC AF Catley, Laurence Weisberg, Ellen Kiziltepe, Tanyel Tai, Yu-Tzu Hideshima, Teru Neri, Paola Tassone, Pierfrancesco Atadja, Peter Chauhan, Dharminder Munshi, Nikhil C. Anderson, Kenneth C. TI Aggresome induction by proteasome inhibitor bortezomib and alpha-tubulin hyperacetylation by tubulin deacetylase (TDAC) inhibitor LBH589 are synergistic in myeloma cells SO BLOOD LA English DT Article ID UNFOLDED PROTEIN RESPONSE; MEDIATED DRUG-RESISTANCE; RECEPTOR MESSENGER-RNA; MARROW STROMAL CELLS; HISTONE DEACETYLASE; MULTIPLE-MYELOMA; MAMMALIAN-CELLS; CANCER CELLS; KAPPA-B; DEGRADATION AB Histone deacetylase (HDAC) inhibitors have shown cytotoxicity as single agents in preclinical studies for multiple myeloma (MM) cells. LBH589 is a novel hydroxamic acid derivative that at low nanomolar concentrations induces apoptosis in MM cells resistant to conventional therapies via caspase activation and poly(ADP-ribose) polymerase (PARP) cleavage. Significant synergistic cytotoxicity was observed with LBH589 in combination with bortezomib against MM cells that were sensitive and resistant to dexamethasone (Dex), as well as primary patient MM cells. LBH589 at low nanomolar concentrations also induced alpha-tubulin hyperacetylation. Aggresome formation was observed in the presence of bortezomib, and the combination of LBH589 plus bortezomib induced the formation of abnormal bundles of hyeracetylated alpha-tubulin but with diminished aggresome size and apoptotic nuclei. These data confirm the potential clinical benefit of combining HDAC inhibitors with proteasome inhibitors, and provide insight into the mechanisms of synergistic anti-MM activity of bortezomib in combination with LBH589. C1 Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. VA Hosp, Boston, MA USA. Novartis Inst Biomed Res, Oncol Res, E Hanover, NJ USA. RP Anderson, KC (reprint author), Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Dept Med Oncol, Mayer Bldg Rm M557,44 Binney St, Boston, MA 02115 USA. EM kenneth_anderson@dfci.harvard.edu RI Catley, Laurence/E-5313-2013 FU NCI NIH HHS [P01 CA78 378, R01 CA50947] NR 59 TC 208 Z9 213 U1 1 U2 5 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 2006 VL 108 IS 10 BP 3441 EP 3449 DI 10.1182/blood-2006-04-016055 PG 9 WC Hematology SC Hematology GA 103VM UT WOS:000241915000036 PM 16728695 ER PT J AU Richardson, PG Blood, E Mitsiades, CS Jagannath, S Zeldenrust, SR Alsina, M Schlossman, RL Rajkumar, SV Desikan, KR Hideshima, T Munshi, NC Kelly-Colson, K Doss, D McKenney, ML Gorelik, S Warren, D Freeman, A Rich, R Wu, AF Olesnyckyj, M Wride, K Dalton, WS Zeldis, J Knight, R Weller, E Anderson, KC AF Richardson, Paul G. Blood, Emily Mitsiades, Constantine S. Jagannath, Sundar Zeldenrust, Steven R. Alsina, Melissa Schlossman, Robert L. Rajkumar, S. Vincent Desikan, K. Raman Hideshima, Teru Munshi, Nikhil C. Kelly-Colson, Kathleen Doss, Deborah McKenney, Mary L. Gorelik, Svetlana Warren, Diane Freeman, Andrea Rich, Rebecca Wu, Anfang Olesnyckyj, Marta Wride, Kenton Dalton, William S. Zeldis, Jerome Knight, Robert Weller, Edie Anderson, Kenneth C. TI A randomized phase 2 study of lenalidomide therapy for patients with relapsed or relapsed and refractory multiple myeloma SO BLOOD LA English DT Article ID HIGH-DOSE CHEMOTHERAPY; THALIDOMIDE PLUS DEXAMETHASONE; NEWLY-DIAGNOSED MYELOMA; COMBINATION THERAPY; DRUG-RESISTANCE; OPEN-LABEL; CELL; BORTEZOMIB; CC-5013; ANALOGS AB This multicenter, open-label, randomized phase 2 study evaluated 2 dose regimens of lenalidomide for relapsed, refractory myeloma. Seventy patients were randomized to receive either 30 mg once-daily or 15 mg twice-daily oral lenalidomide for 21 days of every 28-day cycle. Patients with progressive or stable disease after 2 cycles received dexamethasone. Analysis of the first 70 patients showed increased grade 3/4 myelosuppression in patients receiving 15 mg twice daily (41% versus 13%, P=.03). An additional 32 patients received 30 mg once daily. Responses were evaluated according to European Group for Blood and Marrow Transplantation (EBMT) criteria. Overall response rate (complete, partial, or minor) to lenalidomide alone was 25% (24% for once-daily and 29% for twice-daily lenalidomide). Median overall survival in 30-mg once-daily and twice-daily groups was 28 and 27 months, respectively. Median progressionfree survival was 7.7 months on once-daily versus 3.9 months on twice-daily lenalidomide (P = .2). Dexamethasone was added in 68 patients and 29% responded. Time to first occurrence of clinically significant grade 3/4 myelosuppression was shorter in the twice-daily group (11.8 vs 5.5 months, P = .05). Significant peripheral neuropathy and deep vein thrombosis each occurred in only 3%. Lenalidomide is active and well tolerated in relapsed, refractory myeloma, with the 30-mg once-daily regimen providing the basis for future studies as monotherapy and with dexamethasone. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. St Vincents Comprehens Canc Ctr, New York, NY USA. Mayo Clin, Rochester, MN USA. Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. Celgene, Summit, NJ USA. RP Richardson, PG (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, 44 Binney St, Boston, MA 02115 USA. EM paul_richardson@dfci.harvard.edu OI Rajkumar, S. Vincent/0000-0002-5862-1833 FU NCI NIH HHS [P50 CA100707, P01 CA78373, R01 CA50947] NR 35 TC 334 Z9 341 U1 1 U2 6 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 NOV 15 PY 2006 VL 108 IS 10 BP 3458 EP 3464 DI 10.1182/blood-2006-04-015909 PG 7 WC Hematology SC Hematology GA 103VM UT WOS:000241915000038 PM 16840727 ER PT J AU Pardanani, AD Levine, RL Lasho, T Pikman, Y Mesa, RA Wadleigh, M Steensma, DP Elliott, MA Wolanskyj, AR Hogan, WJ McClure, RF Litzow, MR Gilliland, DG Tefferi, A AF Pardanani, Animesh D. Levine, Ross L. Lasho, Terra Pikman, Yana Mesa, Ruben A. Wadleigh, Martha Steensma, David P. Elliott, Michelle A. Wolanskyj, Alexandra R. Hogan, William J. McClure, Rebecca F. Litzow, Mark R. Gilliland, D. Gary Tefferi, Ayalew TI MPL515 mutations in myeloproliferative and other myeloid disorders: a study of 1182 patients SO BLOOD LA English DT Article ID FAMILIAL POLYCYTHEMIA-VERA; TYROSINE KINASE JAK2; ESSENTIAL THROMBOCYTHEMIA; CLONAL HEMATOPOIESIS; ACTIVATING MUTATION; JAK2V617F MUTATION; V617F MUTATION; MYELOFIBROSIS; METAPLASIA; EXPRESSION AB Recently, a gain-of-function MPL mutation, MPLW515L, was described in patients with JAK2V617F-negative myelofibrosis with myeloid metaplasia (MMM). To gain more information on mutational frequency, disease specificity, and clinical correlates, genomic DNA from 1182 patients with myeloproliferative and other myeloid disorders and 64 healthy controls was screened for MPL515 mutations, regardless of JAK2V617F mutational status: 290 with MMM, 242 with polycythemia Vera, 318 with essential thrombocythemia (ET), 88 with myelodys-plastic syndrome, 118 with chronic myelomonocytic leukemia, and 126 with acute myeloid leukemia (AML). MPL515 mutations, either MPLW515L (n = 17) or a previously undescribed MPLW515K (n = 5), were detected in 20 patients. The diagnosis of patients with mutant MPL alleles at the time of molecular testing was de novo MMM in 12 patients, ET in 4, post-ET MMM in 1, and MMM in blast crisis in 3. Six patients carried the MPLW515L and JAK2V617F alleles concurrently. We conclude that MPLW515L or MPLW515K mutations are present in patients with MMM or ET at a frequency of approximately 5% and 1%, respectively, but are not observed in patients with polycythemia vera (PV) or other myeloid disorders. Furthermore, MPL mutations may occur concurrently with the JAK2V617F mutation, suggesting that these alleles may have functional complementation in myeloproliferative disease. C1 Mayo Clin, Div Hematol, Rochester, MN 55905 USA. Mayo Clin, Div Hematopathol, Rochester, MN 55905 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. RP Tefferi, A (reprint author), Mayo Clin, Div Hematol, 200 1st ST SW, Rochester, MN 55905 USA. EM tefferi.ayalew@mayo.edu OI Steensma, David/0000-0001-5130-9284; Pikman, Yana/0000-0002-5336-0216 NR 24 TC 521 Z9 557 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 2006 VL 108 IS 10 BP 3472 EP 3476 DI 10.1182/blood-2006-04-018879 PG 5 WC Hematology SC Hematology GA 103VM UT WOS:000241915000040 PM 16868251 ER PT J AU Levis, M Brown, P Smith, BD Stine, A Pham, R Stone, R DeAngelo, D Galinsky, I Giles, F Estey, E Kantarjian, H Cohen, P Wang, YF Roesel, J Karp, JE Small, D AF Levis, Mark Brown, Patrick Smith, B. Douglas Stine, Adam Pham, Rosalyn Stone, Richard DeAngelo, Daniel Galinsky, Ilene Giles, Frank Estey, Elihu Kantarjian, Hagop Cohen, Pamela Wang, Yanfeng Roesel, Johannes Karp, Judith E. Small, Donald TI Plasma inhibitory activity (PIA): a pharmacodynamic assay reveals insights into the basis for cytotoxic response to FLT3 inhibitors SO BLOOD LA English DT Article ID TYROSINE KINASE INHIBITOR; ACUTE MYELOID-LEUKEMIA; ALPHA-1-ACID GLYCOPROTEIN; ACTIVATING MUTATIONS; RECEPTOR INHIBITOR; IN-VIVO; PKC412; CELLS; AML; EXPRESSION AB We have developed a useful surrogate assay for monitoring the efficacy of FLT3 inhibition in patients treated with oral FLT3 inhibitors. The plasma inhibitory activity (PIA) for FLT3 correlates with clinical activity in patients treated with CEP-701 and PKC412. Using the PIA assay, along with in vitro phosphorylation and cytotoxicity assays in leukemia cells, we compared PKC412 and its metabolite, CGP52421, with CEP-701. While both drugs could effectively inhibit FLT3 in vitro, CEP-701 was more cytotoxic to primary samples at comparable levels of FLT3 inhibition. PKC412 appears to be more selective than CEP-701 and therefore less effective at Inducing cytotoxicity in primary acute myelold leukemia (AML) samples in vitro. However, the PKC412 metabolite CGP52421 is less selective than its parent compound, PKC412, and is more cytotoxic against primary blast samples at comparable levels of FLT3 inhibition. The plasma inhibitory activity assay represents a useful correlative tool in the development of small-molecule inhibitors. Our application of this assay has revealed that the metabolite CGP52421 may contribute a significant portion of the antileukemia activity observed in patients receiving oral PKC412. Additionally, our results suggest that nonselectivity may constitute an important component of the cytotoxic effect of FLT3 inhibitors in FLT3-mutant AML. C1 Johns Hopkins Univ, Kimmel Canc Ctr, Sidney Kimmel Canc Ctr, Baltimore, MD 21231 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Novartis Oncol, E Hanover, NJ USA. RP Levis, M (reprint author), Johns Hopkins Univ, Kimmel Canc Ctr, Sidney Kimmel Canc Ctr, Baltimore, MD 21231 USA. EM levisma@jhmi.edu FU NCI NIH HHS [CA70970, 2P30 CA 006973-44, CA095600-02, CA100632, CA90668, P30 CA 006973-44] NR 25 TC 90 Z9 94 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 2006 VL 108 IS 10 BP 3477 EP 3483 DI 10.1182/blood-2006-04-015743 PG 7 WC Hematology SC Hematology GA 103VM UT WOS:000241915000041 PM 16857987 ER PT J AU Cooperberg, MR Freedland, SJ Pasta, DJ Elkin, EP Presti, JC Amling, CL Terris, MK Aronson, WJ Kane, CJ Carroll, PR AF Cooperberg, Matthew R. Freedland, Stephen J. Pasta, David J. Elkin, Eric P. Presti, Joseph C., Jr. Amling, Christopher L. Terris, Martha K. Aronson, William J. Kane, Christopher J. Carroll, Peter R. TI Multiinstitutional validation of the UCSF cancer of the prostate risk assessment for prediction of recurrence after radical prostatectomy SO CANCER LA English DT Article DE prostate neoplasm; prostatectomy; prognosis ID RESEARCH ENDEAVOR CAPSURE; PREOPERATIVE NOMOGRAM; DISEASE RECURRENCE; RADIATION-THERAPY; NATURAL-HISTORY; SEARCH DATABASE; OUTCOMES; PROGRESSION; MORTALITY; VELOCITY AB BACKGROUND. The University of California, San Francisco (UCSF) Cancer of the Prostate Risk Assessment (CAPRA) is a novel preoperative index which predicts the risk of biochemical recurrence after radical prostatectomy. The performance of the index is at least as good as the best available instruments based on clinical variables, and the 0 to 10 score is simple to calculate for both clinical and research purposes. This study used a large external dataset to validate CAPRA. METHODS. Data were abstracted from the Shared Equal Access Regional Cancer Hospital (SEARCH) database, a registry of men who underwent radical prostatectomy at 4 Veterans Affairs and 1 active military medical center. Of 2096 men in the database, 1346 (64%) had full data available to calculate the CAPRA score. Performance of the CAPRA score was assessed with proportional hazards regression, survival analysis, and the concordance (c) index. RESULTS. Of the studied patients, 41% were non-Caucasian, and their mean age was 62 years. Twenty-six percent suffered recurrence; median follow-up among patients who did not recur was 34 months. The hazard ratio (HR) for each 1-point increase in CAPRA was 1.39 (95% CI [confidence interval], 1.31-1.46). The 5-year recurrence-free survival rate ranged from 86% for CAPRA 0-1 patients to 21% for CAPRA 7-10 patients. Increasing CAPRA scores were significantly associated with increasing risk of adverse pathologic outcomes. The c-index for CAPRA for the validation set was 0.68, compared with 0.66 for the original development set. CONCLUSIONS. The UCSF-CAPRA accurately predicted both biochemical and pathologic outcomes after radical prostatectomy among a large, diverse, cohort of men. These results validated the effectiveness of this powerful and straightforward instrument. C1 Univ Calif San Francisco, Dept Urol, Program Urol Oncol, Urol Outcomes Res Grp,Comprehens Canc Ctr, San Francisco, CA 94143 USA. Duke Univ, Dept Surg, Div Urol, Durham, NC USA. Stanford Univ, Dept Urol, Sch Med, Stanford, CA 94305 USA. Vet Adm Med Ctr, Urol Sect, Dept Surg, Palo Alto, CA 94304 USA. San Diego Naval Med Ctr, Dept Urol, San Diego, CA USA. Vet Adm Med Ctr, Dept Surg, Urol Sect, Augusta, GA 30904 USA. Med Coll Georgia, Dept Surg, Augusta, GA 30912 USA. Vet & Adm Greater Los Angeles Healthcare Syst, Urol Sect, Dept Surg, Los Angeles, CA USA. Univ Calif Los Angeles, Dept Urol, Sch Med, Los Angeles, CA USA. Vet Adm Med Ctr, Dept Surg, Urol Sect, San Francisco, CA USA. RP Cooperberg, MR (reprint author), Univ Calif San Francisco, Dept Urol, Program Urol Oncol, Urol Outcomes Res Grp,Comprehens Canc Ctr, Box 0738,400 Parnassus Ave,A-633, San Francisco, CA 94143 USA. EM mcooperberg@urology.ucsf.edu RI Cooperberg, Matthew/B-3867-2008; OI Pasta, David/0000-0003-2637-9293; Terris, Martha/0000-0002-3843-7270 FU NCI NIH HHS [P50 CA92131-01A1, R01 CA100938]; PHS HHS [P50 C89520] NR 28 TC 73 Z9 74 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 NOV 15 PY 2006 VL 107 IS 10 BP 2384 EP 2391 DI 10.1002/cncr.22262 PG 8 WC Oncology SC Oncology GA 104DF UT WOS:000241935500009 PM 17039503 ER PT J AU Ryan, DP Appleman, LJ Lynch, T Supko, JG Fidias, P Clark, JW Fishman, M Zhu, AX Enzinger, PC Kashala, O Cusack, J Eder, JP AF Ryan, David P. Appleman, Leonard J. Lynch, Thomas Supko, Jeffrey G. Fidias, Panagiotis Clark, Jeffrey W. Fishman, Mayer Zhu, Andrew X. Enzinger, Peter C. Kashala, Oscar Cusack, James, Jr. Eder, Joseph P. TI Phase I clinical trial of bortezomib in combination with gemcitabine in patients with advanced solid tumors SO CANCER LA English DT Article; Proceedings Paper CT 94th Annual Meeting of the American-Association-for-Cancer-Research CY JUL 11-14, 2003 CL WASHINGTON, DC SP Amer Assoc Canc Res DE bortezomib; cancer; gemcitabine; maximum tolerated dose; proteasome; toxicity ID PROTEASOME INHIBITOR PS-341; NF-KAPPA-B; INDUCED CELL-DEATH; MULTIPLE-MYELOMA; INDUCED APOPTOSIS; CYCLIN; ACTIVATION; CANCER; LINES; RESISTANT AB BACKGROUND. Bortezomib is the first proteasome inhibitor to show preliminary evidence of activity against solid tumors. Findings from preclinical studies prompted a Phase I trial to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLTs) of bortezomib in combination with gemcitabine in patients with recurring/refractory advanced solid tumors. The effect of gemcitabine on proteasome inhibition by bortezomib in whole blood was also investigated. METHODS. Bortezomib was administered as an intravenous bolus injection on Days 1, 4, 8, and 11, with gemcitabine (30-minute infusion) on Days 1 and 8 of a 21-day cycle. Groups of >= 3 patients were evaluated at each dose level. Escalating doses of gemcitabine 500 mg/m(2) to 1000 mg/m(2) with bortezomib 1.0 mg/m(2) to 1.5 mg/m(2) were planned. RESULTS. There were no DLTs in patients receiving bortezomib 1.0 mg/m(2) and gemcitabine 500 mg/m(2) to 1000 mg/m(2) in the first 3 dose levels. Dose-limiting nausea, vomiting, gastrointestinal obstruction, and thrombocytopenia occurred in 4 of 5 evaluable patients in dose level 4 (bortezomib 1.3 mg/m(2), gemcitabine 800 mg/m(2)), establishing bortezomib 1.0 mg/m(2) and gemcitabine 1000 mg/m(2) as the MTD. Most common Grade >= 3 toxicities were neutropenia (6 patients), thrombocytopenia (5 patients), gastrointestinal disorders (6 patients), and general disorders (4 patients) such as fatigue. One patient with nonsmall cell lung carcinoma achieved a partial response and 7 achieved stable disease. Inhibition of 20S proteasome activity by bortezomib was unaffected by gemcitabine coadministration. CONCLUSION. Dosages of bortezomib and gemcitabine suitable for further evaluation of antitumor activity have been established. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. Millennium Pharmaceut, Cambridge, MA USA. RP Ryan, DP (reprint author), 55 Fruit St,YAW 7E, Boston, MA 02114 USA. EM dpryan@partners.org OI Appleman, Leonard/0000-0003-4951-7388 NR 38 TC 43 Z9 44 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 NOV 15 PY 2006 VL 107 IS 10 BP 2482 EP 2489 DI 10.1002/cncr.22264 PG 8 WC Oncology SC Oncology GA 104DF UT WOS:000241935500021 PM 17036355 ER PT J AU Liu, FH Park, PJ Lai, W Maher, E Chakravarti, A Durso, L Jiang, XL Yu, Y Brosius, A Thomas, M Chin, L Brennan, C DePinho, RA Kohane, I Carroll, RS Blacks, PM Johnson, MD AF Liu, Fenghua Park, Peter J. Lai, Weil Maher, Elizabeth Chakravarti, Arnab Durso, Laura Jiang, Xiuli Yu, Yi Brosius, Amanda Thomas, Meredith Chin, Lynda Brennan, Cameron DePinho, Ronald A. Kohane, Isaac Carroll, Rona S. Blacks, Peter M. Johnson, Mark D. TI A genome-wide screen reveals functional gene clusters in the cancer genome and identifies EphA2 as a mitogen in glioblastoma SO CANCER RESEARCH LA English DT Article ID ARRAY CGH DATA; COPY NUMBER; PANCREATIC ADENOCARCINOMA; MICROARRAY ANALYSIS; MOLECULAR SUBTYPES; GASTRIC-CANCER; BREAST-CANCER; EXPRESSION; HYBRIDIZATION; PROGRESSION AB A novel genome-wide screen that combines patient outcome analysis with array comparative genomic hybridization and mRNA expression profiling was developed to identify genes with copy number alterations, aberrant mRNA expression, and relevance to survival in glioblastoma. The method led to the discovery of physical gene clusters within the cancer genome with boundaries defined by physical proximity, correlated mRNA expression patterns, and survival relatedness. These boundaries delineate a novel genomic interval called the functional common region (FCR). Many FCRs contained genes of high biological relevance to cancer and were used to pinpoint functionally significant DNA alterations that were too small or infrequent to be reliably identified using standard algorithms. One such FCR contained the EphA2 receptor tyrosine kinase. Validation experiments showed that EphA2 mRNA overexpression correlated inversely with patient survival in a panel of 21 glioblastomas, and ligand-mediated EphA2 receptor activation increased glioblastoma proliferation and tumor growth via a mitogen-activated protein kinase-dependent pathway. This novel genome-wide approach greatly expanded the list of target genes in glioblastoma and represents a powerful new strategy to identify the upstream determinants of tumor phenotype in a range of human cancers. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Neurol Surg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Ctr Canc, Program Neurooncol, Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Ctr Canc, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Partners Ctr Genet & Genom, Boston, MA 02115 USA. Dana Farber Canc Inst, Ctr Appl Canc Sci, Belfer Fdn Inst Innovat Canc Sci, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. Childrens Hosp, Informat Program, Boston, MA 02115 USA. RP Johnson, MD (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Neurol Surg, 75 Francis St, Boston, MA 02115 USA. EM mjohnson27@partners.org RI Kohane, Isaac Kohane/K-3716-2012; OI Kohane, Isaac Kohane/0000-0003-2192-5160; Brennan, Cameron/0000-0003-4064-8891 FU NCI NIH HHS [P01CA095616, R01 CA99041]; NIGMS NIH HHS [K25 GM067825]; NINDS NIH HHS [K08 NS43482]; NLM NIH HHS [U54LM008748]; PHS HHS [NIH T32] NR 45 TC 63 Z9 66 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 2006 VL 66 IS 22 BP 10815 EP 10823 DI 10.1158/0008-5472.CAN-06-1408 PG 9 WC Oncology SC Oncology GA 108UJ UT WOS:000242264400023 PM 17090523 ER PT J AU Kosharskyy, B Solban, N Chang, SK Rizvi, I Chang, YC Hasan, T AF Kosharskyy, Boleslav Solban, Nicolas Chang, Sung K. Rizvi, Imran Chang, Yuchiao Hasan, Tayyaba TI A mechanism-based combination therapy reduces local tumor growth and metastasis in an orthotopic model of prostate cancer SO CANCER RESEARCH LA English DT Article ID ANGIOGENESIS INHIBITOR TNP-470; ENDOTHELIAL-CELL GROWTH; PHASE-I TRIAL; PHOTODYNAMIC THERAPY; MAMMARY-CARCINOMA; 9L GLIOSARCOMA; AGENT TNP-470; RADIOTHERAPY; VASCULATURE; OXYGENATION AB Therapy-induced stimulation of angiogenic molecules can promote tumor angiogenesis leading to enhanced tumor growth and cancer metastasis. Several standard and emerging therapies, such as radiation and photodynamic therapy (PDT), can induce angiogenic molecules, thus limiting their effectiveness. PDT is approved for the treatment of several cancers; however, its induction of vascular endothelial growth factor (VEGF) creates conditions favorable to enhanced tumor growth and metastasis, therefore mitigating its cytotoxic and antivascular effects. This is the first report showing that subcurative PDT in an orthotopic model of prostate cancer (LNCaP) increases not only VEGF secretion (2.1-fold) but also the fraction of animals with lymph node metastases. PDT followed by administration of an antiangiogenic agent, TNP-470, abolished this increase and reduced local tumor growth. On the other hand, administration of TNP-470 before PDT was less effective at local tumor control. In addition, animals in all groups, except in the PDT + TNP-470 group, had a weight loss of > 3 g at the time of sacrifice; the weight of the animals in the PDT + TNP-470 group did not change. The significant reduction (P < 0.05) in tumor weight and volume observed between the PDT + TNP-470 group and the control group suggests that the combination of PDT and antiangiogenic treatment administered in the appropriate sequence was not only more effective at controlling local tumor growth and metastases but also reduced disease-related toxicities. Such molecular response-based combinations merit further investigations as they enhance both monotherapies and lead to improved treatment outcomes. C1 Harvard Univ, Wellman Ctr Photomed, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. Mt Sinai Hosp, Dept Anesthesiol, New York, NY USA. RP Hasan, T (reprint author), Harvard Univ, Wellman Ctr Photomed, Massachusetts Gen Hosp, Sch Med, 40 Blossom St, Boston, MA 02114 USA. EM thasan@partners.org OI Rizvi, Imran/0000-0001-9673-4700 FU NCI NIH HHS [P01 CA84203]; NIBIB NIH HHS [R01 EB00664] NR 43 TC 48 Z9 54 U1 2 U2 10 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 2006 VL 66 IS 22 BP 10953 EP 10958 DI 10.1158/0008-5472.CAN-06-1793 PG 6 WC Oncology SC Oncology GA 108UJ UT WOS:000242264400040 PM 17108133 ER PT J AU Chen, ZY AF Chen, Zheng-Yi TI Cell cycle, differentiation and regeneration - Where to begin? SO CELL CYCLE LA English DT Review DE hair cell; retinoblastoma; regeneration; cell cycle; differentiation; maturation; survival; deafness ID EAR HAIR-CELLS; INNER-EAR; RETINOBLASTOMA PROTEIN; ACOUSTIC TRAUMA; FATE DETERMINATION; BALANCE EPITHELIA; PROLIFERATION; GENE; KINASE; ORGAN AB Hair cells, the sensory cells of inner ear, perform essential functions in hearing and balance. However, mammalian hair cells, like most of the CNS neurons, lack the capacity to regenerate. This is in sharp contrast to lower vertebrates in which hair cell regeneration occurs spontaneously through cell division of supporting cells, which leads to hearing restoration. It is believed that the lack of regeneration in mammals is, to a large degree, due to the block of cell cycle reentry imposed by negative cell growth genes in the inner ear. Recent studies have identified retinoblastoma gene, a well-known tumor suppressor, as the key gene involved in cell cycle exit of inner ear sensory cells. In the inner ear of pRb conditional knockout mice, hair cells undergo continuous cell division, and at the same time differentiate and become functional. Cell division continues in early postnatal cochlea and adult vestibule. Remarkably, the vestibular hair cells without pRb survive, and function at both the cellular and system levels. The time course and effects of pRb inhibition shows that there is a separation between the roles of pRb in cell cycle exit, and subsequent maturation and apoptosis. Those studies reveal distinctly different roles of pRb in the cochlear and vestibular sensory epithelia. The review discusses additional areas to be studied for regeneration of mature hair cells, and highlights the importance of transient and reversible block of pRb function as one of the routes to be explored for regeneration. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurol Serv,MGH HMS Ctr Nervous Syst Repair, Boston, MA 02114 USA. Harvard Univ, Program Neurosci, Sch Med, Boston, MA 02114 USA. RP Chen, ZY (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurol Serv,MGH HMS Ctr Nervous Syst Repair, Thier 425,55 Fruit St, Boston, MA 02114 USA. EM zhengyi@helix.mgh.harvard.edu NR 34 TC 9 Z9 11 U1 0 U2 3 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD NOV 15 PY 2006 VL 5 IS 22 BP 2609 EP 2612 DI 10.4161/cc.5.22.3503 PG 4 WC Cell Biology SC Cell Biology GA 117UA UT WOS:000242897600013 PM 17106260 ER PT J AU Dalton, W Anderson, KC AF Dalton, William Anderson, Kenneth C. TI Synopsis of a roundtable on validating novel therapeutics for multiple myeloma SO CLINICAL CANCER RESEARCH LA English DT Review ID IN-VIVO MODEL; MEDIATED DRUG-RESISTANCE; CELL-LINES; ANTITUMOR-ACTIVITY; MURINE MODEL; MICE; IMMUNOGLOBULIN; APOPTOSIS; THERAPY; GROWTH AB Purpose: With the identification of new molecular targets and pathways, many new therapeutic approaches are being identified for potential application in the treatment of multiple myeloma. New chemical compounds and biologics have been developed against molecular targets with substantial scientific evidence that these targets are involved in myeloma development, progression, or relapse. To safely and rapidly bring these advances to bear on the disease, new preclinical models in cells and animals need to be established, as well as prioritization and standardization in current preclinical and clinical validation. An experts' roundtable was convened in November 2005 to discuss shortcomings in current preclinical models and discuss what models are needed to best validate therapeutics and combinations of therapies for multiple myeloma. Conclusions: This exciting event brought together experts in compound validation, preclinical development, and experts in multiple myeloma from academic institutions and the pharmaceutical and biotechnology industries. The goals were to evaluate an algorithm for therapeutic validation and discuss in vitro modeling for target discovery, animal models for preclinical development, and models for testing drug combinations. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. H Lee Moffit Canc Ctr & Res Inst, Tampa, FL USA. RP Anderson, KC (reprint author), Dana Farber Canc Inst, 44 Binney St,Mayer 557, Boston, MA 02115 USA. EM Kenneth_Anderson@dfci.harvard.edu NR 44 TC 18 Z9 19 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV 15 PY 2006 VL 12 IS 22 BP 6603 EP 6610 DI 10.1158/1078-0432.CCR-06-1489 PG 8 WC Oncology SC Oncology GA 108TY UT WOS:000242263300004 PM 17121878 ER PT J AU Cusack, JC Liu, R Xia, LJ Chao, TH Pien, C Niu, W Palombella, VJ Neuteboom, STC Palladino, MA AF Cusack, James C., Jr. Liu, Rong Xia, Lijun Chao, Ta-Hsiang Pien, Christine Niu, Wei Palombella, Vito J. Neuteboom, Saskia T. C. Palladino, Michael A. TI NPI-0052 enhances tumoricidal response to conventional cancer therapy in a colon cancer model SO CLINICAL CANCER RESEARCH LA English DT Article ID PROTEASOME INHIBITOR PS-341; NF-KAPPA-B; COLORECTAL-CANCER; SALINOSPORAMIDE-A; APOPTOSIS; MECHANISMS; CELLS; CHEMOSENSITIVITY; BORTEZOMIB AB Purpose: In the current study, we examine the effects of a novel proteasome inhibitor, NPI-0052 (salinosporamide A), on proteasome function and nuclear factor-kappa B activation and evaluate its ability to enhance treatment response in colon cancer xenografts when administered orally. Experimental Design: The effects of treatment on nuclear factor-kappa B activation, cell cycle regulation, and apoptosis were determined. The pharmacodynamic effect of NPI-0052 on 20S proteasome function was assayed in vivo following oral and i.v. drug administration and compared with treatment with bortezomib. The effect of combined treatment with chemotherapy was determined in a colon cancer xenograft model. Results: We found that NPI-0052 is a potent, well-tolerated proteasome inhibitor that has pharmacodynamic properties distinct from bortezomib in that it achieves significantly higher and more sustained levels of proteasome inhibition. When combined with chemotherapy, NPI-0052 increases apoptosis and shifts cells toward G(2) cell cycle arrest. When added to chemotherapy in vivo [using combinations of 5-fluorouracil (5-FU), CPT-11, Avastin (bevacizumab), leucovorin, and oxaliplatin], NPI-0052 significantly improved the tumoricidal response and resulted in a 1.8-fold increased response to CPT-11, 5-FU, and leucovorin triple-drug combination (P = 0.0002, t test), a 1.5-fold increased response to the oxaliplatin, 5-FU, and,leucovorin triple-drug combination (P = 0.013, t test), and a 2.3-fold greater response to the CPT-11, 5-FU, leucovorin, and Avastin regimen (P = 0.00057). Conclusions:The high level of proteasome inhibition achieved by NPI-0052 is well tolerated and significantly improves the tumoricidal response to multidrug treatment in a colon cancer xenograft model. Further evaluation of this novel proteasome inhibitor in clinical trials is indicated. C1 Massachusetts Gen Hosp, Div Surg Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Nereus Pharmaceut, San Diego, CA USA. RP Cusack, JC (reprint author), Massachusetts Gen Hosp, Div Surg Oncol, Yawkey 7th Floor,55 Fruit St, Boston, MA 02114 USA. EM jcusack@partners.org FU NCI NIH HHS [CA77278, CA98871] NR 20 TC 71 Z9 73 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV 15 PY 2006 VL 12 IS 22 BP 6758 EP 6764 DI 10.1158/1078-0432.CCR-06-1151 PG 7 WC Oncology SC Oncology GA 108TY UT WOS:000242263300022 PM 17121896 ER PT J AU Redjal, N Chan, JA Segal, RA Kung, AL AF Redjal, Navid Chan, Jennifer A. Segal, Rosalind A. Kung, Andrew L. TI CXCR4 inhibition synergizes with cytotoxic chemotherapy in gliomas SO CLINICAL CANCER RESEARCH LA English DT Article ID CHEMOKINE RECEPTOR CXCR4; BRAIN-TUMORS; HUMAN GLIOBLASTOMA; STEM-CELLS; EXPRESSION; PROLIFERATION; METASTASIS; SURVIVAL; GROWTH; SDF1 AB Purpose: The chemokine receptor CXCR4 is expressed in many different cancers. In malignant brain tumors, CXCR4 signaling has been implicated in tumor growth, survival, and migration, and pharmacologic inhibition of CXCR4 results in decreased tumor growth in preclinical models. To understand how CXCR4 inhibitors may be incorporated into clinical therapy, we examined determinants of responsiveness to CXCR4 inhibition. Because optimal use of CXCR4 inhibition will likely be a part of multimodality therapy, we also investigated the efficacy of CXCR4 inhibition combined with conventional cytotoxic chemotherapy. Experimental Design: CXCR4 protein levels and responsiveness to the CXCR4 inhibitor AMD3100 were determined in a panel of glioblastoma multiforme cell lines. The effects of AMD3100, alone or in combination with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), on cell growth were determined for several of these cell lines in vitro. We used an orthotopic model of glioblastoma multiforme to evaluate the antitumor efficacy of AMD3100 combined with BCNU in vivo. Results: The level of CXCR4 protein expression in glioblastoma multiforme cells predicts the dose at which there is a response to AMD3100; cells that express higher levels of CXCR4 protein require higher doses for equivalent response. In all cell lines tested, treatment of glioblastoma multiforme cells with BCNU followed by AMD3100 results in synergistic antitumor efficacy in vitro. This synergy can also be seen in an orthotopic glioblastoma multiforme model. Treatment with subtherapeutic doses of BCNU in combination with AMD3100 results in tumor regression in vivo, and this reflects both increased apoptosis and decreased proliferation following combination therapy. Conclusion: These studies support testing CXCR4 inhibitors in patients with glioblastoma multiforme and establish that inhibition of CXCR4 synergizes with conventional cytotoxic therapies in a clinically relevant combinatorial strategy. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. RP Kung, AL (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St,Mayer 649, Boston, MA 02115 USA. EM andrew_kung@dfci.harvard.edu OI Kung, Andrew/0000-0002-9091-488X FU NICHD NIH HHS [K08 HD048595]; NINDS NIH HHS [NS377057] NR 20 TC 91 Z9 96 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 NOV 15 PY 2006 VL 12 IS 22 BP 6765 EP 6771 DI 10.1158/1078-0432.CCR-06-1372 PG 7 WC Oncology SC Oncology GA 108TY UT WOS:000242263300023 PM 17121897 ER PT J AU Liu, TC Zhang, TG Fukuhara, H Kuroda, T Todo, T Canron, X Bikfalvi, A Martuza, RL Kurtz, A Rabkin, SD AF Liu, Ta-Chiang Zhang, Tingguo Fukuhara, Hiroshi Kuroda, Toshihiko Todo, Tomoki Canron, Xavier Bikfalvi, Andreas Martuza, Robert L. Kurtz, Andreas Rabkin, Samuel D. TI Dominant-negative fibroblast growth factor receptor expression enhances antitumoral potency of oncolytic herpes simplex virus in neural tumors SO CLINICAL CANCER RESEARCH LA English DT Article ID MALIGNANT GLIOMA; VASCULAR DEVELOPMENT; GENE-TRANSFER; IN-VITRO; ANGIOGENESIS; CELLS; CANCER; REPLICATION; THERAPY; MUTANT AB Purpose: Oncolytic herpes simplex viruses (HSV) appear to be a promising platform for cancer therapy. However, efficacy as single agents has thus far been unsatisfactory. Fibroblast growth factor (FGF) signaling is important for the growth and migration of endothelial and tumor cells. Here, we examine the strategy of arming oncolytic HSV with a dominant-negative FGF receptor (dn FGFR) that targets the FGF signaling pathway. Experimental Design: A mouse Nf1:p53 malignant peripheral nerve sheath tumor (MPNST) cell line expressing dn FGFR was generated by transfection. The effects of dn FGFR expression on cell growth and migration in vitro and tumor formation in vivo were determined. The dn FGFR transgene was then inserted into oncolytic HSV G47 Delta using a bacterial artificial chromosome construction system. Antitumoral and antiangiogenic activities of bG47 Delta-dnFGFR were examined. Results: MPNST 61E4 cells expressing dnFGFR grew less well than parental control cells. bG47 Delta-dnFGFR showed enhanced killing of both tumor (human U87 glioma and F5 malignant meningioma cells and murine MPNST 61E4 and 37-3-18-4 cells) and proliferating endothelial cells (human umbilical vascular endothelial cell and Py-4-1) in vitro compared with the control vector bG47 Delta-empty without inhibiting viral replication. In vivo, bG47 Delta-dnFGFR was more efficacious than its nonexpressing parent bG47 Delta-empty at inhibiting tumor growth and angiogenesis in both human U87 glioma and mouse 37-3-18-4 MPNST tumors in nude mice. Conclusions: By using multiple therapeutic mechanisms, including destruction of both tumor cells and tumor endothelial cells, an oncolytic HSV encoding dn FGFR enhances antitumor efficacy. This strategy can be applied to other oncolytic viruses and for clinical translation. C1 Massachusetts Gen Hosp, Mol Neurosurg Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Bordeaux 1, INSERM, E0113, F-33405 Talence, France. RP Rabkin, SD (reprint author), Massachusetts Gen Hosp, Mol Neurosurg Lab, CPZN-3800 Simches Res Bldg,185 Cambridge St, Boston, MA 02114 USA. EM rabkin@helix.mgh.harvard.edu RI rabkin, samuel/C-2443-2012; OI rabkin, samuel/0000-0003-2344-2795; Kuroda, Toshihiko/0000-0001-6660-8930 FU NINDS NIH HHS [R01 NS032677] NR 46 TC 35 Z9 36 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV 15 PY 2006 VL 12 IS 22 BP 6791 EP 6799 DI 10.1158/1078-0432.CCR-06-0263 PG 9 WC Oncology SC Oncology GA 108TY UT WOS:000242263300026 PM 17121900 ER PT J AU Francis, LK Alsayed, Y Leleu, X Jia, XY Singha, UK Anderson, J Timm, M Go, HN Lu, GW Huston, A Ehrlich, LA Dimmock, E Lentzsch, S Hideshima, T Roodman, GD Anderson, KC Ghobrial, IM AF Francis, Lanie K. Alsayed, Yazan Leleu, Xavier Jia, Xiaoying Singha, Ujjal K. Anderson, Judith Timm, Michael Go, Hai N. Lu, Ganwei Huston, Alissa Ehrlich, Lori A. Dimmock, Elizabeth Lentzsch, Suzanne Hideshima, Teru Roodman, G. David Anderson, Kenneth C. Ghobrial, Irene M. TI Combination mammalian target of rapamycin inhibitor rapamycin and HSP90 inhibitor 17-allylamino-17-demethoxygeldanamycin has synergistic activity in multiple myeloma SO CLINICAL CANCER RESEARCH LA English DT Article ID CYCLIN-D DYSREGULATION; IN-VIVO; THERAPEUTIC IMPLICATIONS; OSTEOCLAST FORMATION; SIGNAL-TRANSDUCTION; CANCER-THERAPY; CELLS; PATHWAY; EXPRESSION; AKT AB Purpose: The phosphatidylinositol 3-kinase/AKT/mammalian target of rapamycin (mTOR) pathway and the heat shock protein family are up-regulated in multiple myeloma and are both regulators of the cyclin D/retinoblastoma pathway, a critical pathway in multiple myeloma. Inhibitors of mTOR and HSP90 protein have showed in vitro and in vivo single-agent activity in multiple myeloma. Our objective was to determine the effects of the mTOR inhibitor rapamycin and the HSP90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG) on multiple myeloma cells. Experimental Design: Multiple myeloma cell lines were incubated with rapamycin (0.1-100 nmol/L) and 17-AAG (100-600 nmol/L) alone and in combination. Results: In this study, we showed that the combination of rapamycin and 17-AAG synergistically inhibited proliferation, induced apoptosis and cell cycle arrest, induced cleavage of poly(ADPribose) polymerase and caspase-8/caspase-9, and dysregulated signaling in the phosphatidylinositol 3-kinase/AKT/mTOR and cyclin D1/retinoblastoma pathways. In addition, we showed that both 17-AAG and rapamycin inhibited angiogenesis and osteoclast formation, indicating that these agents target not only multiple myeloma cells but also the bone marrow microenvironment. Conclusions: These studies provide the basis for potential clinical evaluation of this combination for multiple myeloma patients. C1 Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. Univ Pittsburgh, Inst Canc, Dept Internal Med, Div Hematol Oncol, Pittsburgh, PA USA. Harvard Univ, Sch Med, Boston, MA USA. Mayo Clin, Coll Med, Rochester, MN USA. RP Ghobrial, IM (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, 44 Binney St,Mayer 548A, Boston, MA 02115 USA. EM irene_ghobrial@dfci.harvard.edu NR 37 TC 64 Z9 66 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV 15 PY 2006 VL 12 IS 22 BP 6826 EP 6835 DI 10.1158/1078-0432.CCR-06-1331 PG 10 WC Oncology SC Oncology GA 108TY UT WOS:000242263300030 PM 17121904 ER PT J AU Duan, ZF Bradner, JE Greenberg, E Levine, R Foster, R Mahoney, J Seiden, MV AF Duan, Zhenfeng Bradner, James E. Greenberg, Edward Levine, Ross Foster, Rosemary Mahoney, Jennifer Seiden, Michael V. TI SD-1029 inhibits signal transducer and activator of transcription 3 nuclear translocation SO CLINICAL CANCER RESEARCH LA English DT Article ID CONSTITUTIVE SIGNAL TRANSDUCER; OVARIAN-CARCINOMA CELLS; ACUTE MYELOID-LEUKEMIA; BREAST-CANCER CELLS; PACLITAXEL RESISTANCE; ACTIVATING MUTATION; CONFERS RESISTANCE; MOLECULAR TARGETS; STAT PROTEINS; V-SRC AB Purpose: Signal transducer and activator of transcription 3 (Stat3) proteins have important roles in cancer cell survival and proliferation. Recent studies show that aberrant Stat3 activation promotes tumor growth and survival in several human cancers, and thus, presents an attractive pathway for the development of targeted anticancer therapy. Stat3 is a DNA-binding transcription factor, and thus, its function depends on cytoplasmic to nuclear translocation. To discover novel inhibitors of the Stat3 signaling pathway, we designed a cell-based screening assay capable of identifying compounds that inhibit Stat3 nuclear translocation and activity. Experimental Design: Cell-based fluorescence microscope screening and quantitative measurement of enhanced green fluorescent protein - Stat3 nuclear translocation assays were used to identify novel Stat3 inhibitors. The effects of identified Stat3 inhibitors on Janus kinase (Jak), Stat3 expression, and activation were determined by Western blotting and kinase in vitro autophosphorylation assay. The effects of identified Stat3 inhibitors on cell growth was evaluated by cell proliferation assay and apoptosis assay. Results: Among the National Cancer Institute Diversity set, a 2,000-member library of bioactive small molecules, we identified SD-1029 as a micromolar inhibitor of IL-6 or oncostatin-induced Stat3 nuclear translocation. Biochemical analysis shows that SD-1029 inhibits tyrosyl phosphorylation of Stat3 implicating SD-1029 as an inhibitor of Jak. Further analysis shows that this compound inhibits tyrosyl phosphorylation of the Jak2 isoenzyme. The antiapoptotic proteins Bcl-X-L and survivin, target proteins of activated Stat3, are down-regulated by SD-1029 resulting in the induction of apoptosis in several human breast and ovarian cancer cell lines. SD-1029 also enhances apoptosis induced by paclitaxel in ovarian cancer cells. Conclusions: These results show that SD-1029 directly abrogates the Jak-Stat3 signaling pathway in human cancer cells expressing constitutively active Stat, and add to the growing literature that validates this pathway as a viable target for further drug development. Finally, SD-1029 may represent a suitable prototype for structural optimization and exploration as a therapeutic lead. C1 Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. Harvard Univ, Broad Inst, Chem Biol Program, Cambridge, MA 02138 USA. MIT, Cambridge, MA 02139 USA. RP Duan, ZF (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, 1008 Jackson Bldg,100 Blossom St, Boston, MA 02114 USA. EM zduan@partners.org FU NCI NIH HHS [1K24 CA109416-01A1, 1P50CA105009] NR 37 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 NOV 15 PY 2006 VL 12 IS 22 BP 6844 EP 6852 DI 10.1158/1078-0432.CCR-06-1330 PG 9 WC Oncology SC Oncology GA 108TY UT WOS:000242263300032 PM 17121906 ER PT J AU Linas, BP Zheng, H Losina, E Rockwell, A Walensky, RP Cranston, K Freedberg, KA AF Linas, Benjamin P. Zheng, Hui Losina, Elena Rockwell, Annette Walensky, Rochelle P. Cranston, Kevin Freedberg, Kenneth A. TI Optimizing resource allocation in United States AIDS drug assistance programs SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; HIV DISEASE; VIRAL LOAD; CELL COUNT; INFECTION; CARE; PREDICTORS; ACCESS; ERA AB Background. US acquired immunodeficiency syndrome (AIDS) Drug Assistance programs (ADAPs) provide medications to low-income patients with human immunodeficiency virus ( HIV) infection/AIDS. Nationally, ADAPs are in a fiscal crisis. Many states have instituted waiting lists, often serving clients on a first-come, first-served basis. We hypothesized that CD4 cell count-based ADAP eligibility would improve ADAP outcomes, allowing them to serve more-diverse patient populations and to prioritize persons who are at greatest risk of HIV-related mortality. Methods. We used Massachusetts ADAP administrative data to create a retrospective cohort of Massachusetts ADAP clients from fiscal year 2003. We then used a model-based analysis to apply potential eligibility criteria for a limited program and to compare characteristics of patients included under CD4 cell count-based and first-come, first-served eligibility criteria. Results. In fiscal year 2003, Massachusetts ADAPs served 3560 clients at a direct cost of $10.3 million. With use of CD4 cell count-based eligibility (with an eligibility criterion of a current or nadir CD4 cell count <= 350 cells/mu L), it would have served 2253 clients (37% fewer than in fiscal year 2003) and appreciated savings of $2.7 million. Given the same budget constraint and using first-come, first-served eligibility, Massachusetts ADAPs would have served 2406 clients (32% fewer than in fiscal year 2003). The first-come, first-served approach would have excluded patients with median CD4 cell count of 257 cells/mu L (interquartile range, 124-377 cells/mu L) in favor of serving patients with median CD4 cell count of 659 cells/mu L (interquartile range, 511-841 cells/mu L). In addition, a CD4 cell count-based scheme would have served a greater proportion of nonwhite individuals (65% vs. 55%;), non-English speakers (24% vs. 19%;), and unemployed people (69% vs. 61%;), P <.0001 Pp. 03 Pp. 0009 compared with the population that would have been served by a first-come, first-served policy. Conclusions. With limited resources, ADAPs will serve more- diverse populations and patients with significantly more advanced HIV disease by using CD4 cell count-based enrollment criteria rather than a first-come, first-served approach. C1 Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Massachusetts Gen Hosp, Harvard Ctr AIDS Res, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Epidemiol, Boston, MA 02115 USA. Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. Massachusetts Dept Publ Hlth AIDS Bur, Boston, MA USA. RP Linas, BP (reprint author), Massachusetts Gen Hosp, Div Gen Med, 50 Staniford St,9th Fl, Boston, MA 02114 USA. EM blinas@partners.org OI Walensky, Rochelle P./0000-0002-8795-379X FU NIAID NIH HHS [R01 AI42006, K23 AI001794, K23 AI01794, K24 AI062476, K25 AI050436, K25 AI50436, P30 AI060354, R01 AI042006]; PHS HHS [T32 HP11001-18] NR 27 TC 7 Z9 7 U1 2 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD NOV 15 PY 2006 VL 43 IS 10 BP 1357 EP 1364 DI 10.1086/508657 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 096UU UT WOS:000241403100021 PM 17051505 ER PT J AU Bardeesy, N Cheng, KH Berger, JH Chu, GC Pahler, J Olson, P Hezel, AF Horner, J Lauwers, GY Hanahan, D DePinho, RA AF Bardeesy, Nabeel Cheng, Kuang-hung Berger, Justin H. Chu, Gerald C. Pahler, Jessica Olson, Peter Hezel, Aram F. Horner, James Lauwers, Gregory Y. Hanahan, Douglas DePinho, Ronald A. TI Smad4 is dispensable for normal pancreas development yet critical in progression and tumor biology of pancreas cancer SO GENES & DEVELOPMENT LA English DT Article DE Smad4; pancreatic cancer; epithelial-to-mesenchymal transition mouse models; TGF-beta ID TRANSFORMING-GROWTH-FACTOR; FACTOR-BETA RECEPTOR; CARCINOMA-CELL-LINES; TGF-BETA; DUCTAL ADENOCARCINOMA; ENHANCED EXPRESSION; DECREASED SURVIVAL; INVASIVE PHENOTYPE; JUVENILE POLYPOSIS; SUPPRESSOR GENE AB SMAD4 is inactivated in the majority of pancreatic ductal adenocarcinomas (PDAC) with concurrent mutational inactivation of the INK4A/ARF tumor suppressor locus and activation of the KRAS oncogene. Here, using genetically engineered mice, we determined the impact of SMAD4 deficiency on the development of the pancreas and on the initiation and/or progression of PDAC-alone or in combination with PDAC-relevant mutations. Selective SMAD4 deletion in the pancreatic epithelium had no discernable impact on pancreatic development or physiology. However, when combined with the activated KRAS(G12D) allele, SMAD4 deficiency enabled rapid progression of KRAS(G12D)-initiated neoplasms. While KRAS(G12D) alone elicited premalignant pancreatic intraepithelial neoplasia (PanIN) that progressed slowly to carcinoma, the combination of KRAS(G12D) and SMAD4 deficiency resulted in the rapid development of tumors resembling intraductal papillary mucinous neoplasia (IPMN), a precursor to PDAC in humans. SMAD4 deficiency also accelerated PDAC development of KRAS(G12D) INK4A/ARF heterozygous mice and altered the tumor phenotype; while tumors with intact SMAD4 frequently exhibited epithelial-to-mesenchymal transition (EMT), PDAC null for SMAD4 retained a differentiated histopathology with increased expression of epithelial markers. SMAD4 status in PDAC cell lines was associated with differential responses to transforming growth factor-beta (TGF-beta) in vitro with a subset of SMAD4 wild-type lines showing prominent TGF-beta-induced proliferation and migration. These results provide genetic confirmation that SMAD4 is a PDAC tumor suppressor, functioning to block the progression of KRAS(G12D)-initiated neoplasms, whereas in a subset of advanced tumors, intact SMAD4 facilitates EMT and TGF-beta-dependent growth. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Ctr Appl Canc Sci, Inst Innovat Canc Sci, Belfer Fdn, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Univ Calif San Francisco, Ctr Comprehens Canc, Dept Biochem & Biophys, San Francisco, CA 94143 USA. Univ Calif San Francisco, Ctr Diabet, San Francisco, CA 94143 USA. Massachusetts Gen Hosp, Dept Pathol, Gastrointestinal Pathol Serv, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med & Genet, Boston, MA 02115 USA. RP Bardeesy, N (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. EM nelbardeesy@partners.org; Ron_depinho@dfci.harvard.edu FU NCI NIH HHS [P01 CA117969-01, 5U01CA84313-08, K01 CA104647, P01 CA117969, U01 CA084313] NR 60 TC 280 Z9 289 U1 3 U2 12 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD NOV 15 PY 2006 VL 20 IS 22 BP 3130 EP 3146 DI 10.1101/gad.1478706 PG 17 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 106XL UT WOS:000242135200009 PM 17114584 ER PT J AU Wu, YL Dai, XQ Li, Q Chen, CX Mai, WY Hussain, Z Long, WT Montalbetti, N Li, GC Glynne, R Wang, SH Cantiello, HF Wu, GQ Chen, XZ AF Wu, Yuliang Dai, Xiao-Qing Li, Qiang Chen, Carl X. Mai, Weiyi Hussain, Zahir Long, Wentong Montalbetti, Nicolas Li, Guochun Glynne, Richard Wang, Shaohua Cantiello, Horacio F. Wu, Guanqing Chen, Xing-Zhen TI Kinesin-2 mediates physical and functional interactions between polycystin-2 and fibrocystin SO HUMAN MOLECULAR GENETICS LA English DT Article ID KIDNEY-DISEASE PROTEIN; RENAL EPITHELIAL-CELLS; LEFT-RIGHT ASYMMETRY; PRIMARY CILIA; INTRAFLAGELLAR TRANSPORT; SUPERFAMILY PROTEIN; PKD2 INTERACTS; KIF3A SUBUNIT; SENSORY CILIA; GENE-PRODUCT AB Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in PKD1, encoding polycystin-1 (PC1), or PKD2 (polycystin-2, PC2). Autosomal recessive PKD (ARPKD) is caused by mutations in PKHD1, encoding fibrocystin/polyductin (FPC). No molecular link between ADPKD and ARPKD has been determined. Here, we demonstrated, by yeast two-hybrid and biochemical assays, that KIF3B, a motor subunit of kinesin-2, associates with PC2 and FPC. Co-immunoprecipitation experiments using Madin-Darby canine kidney (MDCK) and inner medullary collecting duct (IMCD) cells and human kidney revealed that PC2 and KIF3B, FPC and KIF3B and, furthermore, PC2 and FPC are endogenously in the same complex(es), though no direct association between the PC2 and FPC intracellular termini was detected. In vitro binding and Far Western blot experiments demonstrated that PC2 and FPC are in the same complex only if KIF3B is present, presumably by forming a PC2-KIF3B-FPC complex. This was supported by our observation that altering KIF3B level in IMCD cells by over-expression or siRNA significantly affected complexing between PC2 and FPC. Immunofluorescence experiments showed that PC2, FPC and KIF3B partially co-localized in primary cilia of over-confluent and perinuclear regions of sub-confluent cells. Furthermore, KIF3B mediated functional modulation of purified PC2 channels by FPC in a planer lipid bilayer electrophysiology system. The FPC C-terminus substantially stimulated PC2 channel activity in the presence of KIF3B, whereas FPC or KIF3B alone had no effect. Taken together, we discovered that kinesin-2 is a linker between PC2 and FPC and mediates the regulation of PC2 channel function by FPC. Our study may be important for elucidating common molecular pathways for PKD of different genotypes. C1 Univ Alberta, Dept Physiol, Membrane Prot Res Grp, Edmonton, AB T6G 2H7, Canada. Univ Alberta, Dept Surg, Edmonton, AB T6G 2H7, Canada. Jimei Univ, Sch Mech Engn, Fujian, Peoples R China. Vanderbilt Univ, Dept Med, Nashville, TN USA. Univ Buenos Aires, Fac Farm & Bioquim, Lab Canales Ion, RA-1113 Buenos Aires, DF, Argentina. Novartis Res Fdn, Genom Inst, San Diego, CA USA. Massachusetts Gen Hosp, Renal Unit, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. RP Chen, XZ (reprint author), Univ Alberta, Dept Physiol, Membrane Prot Res Grp, 7-29 Med Sci Bldg, Edmonton, AB T6G 2H7, Canada. EM xzchen@ualberta.ca OI Montalbetti, Nicolas/0000-0003-2897-9540; Long, Wentong/0000-0003-4650-8064 NR 47 TC 70 Z9 76 U1 1 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD NOV 15 PY 2006 VL 15 IS 22 BP 3280 EP 3292 DI 10.1093/hmg/ddl404 PG 13 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 099XF UT WOS:000241629900002 PM 17008358 ER PT J AU Valicenti, RK DeSilvio, M Hanks, GE Porter, A Brereton, H Rosenthal, SA Shipley, WU Sandler, HM AF Valicenti, Richard K. DeSilvio, Michelle Hanks, Gerald E. Porter, Arthur Brereton, Harmar Rosenthal, Seth A. Shipley, William U. Sandler, Howard M. TI Posttreatment prostatic-specific antigen doubling time as a surrogate endpoint for prostate cancer-specific survival: An analysis of radiation therapy oncology group protocol 92-02 SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE prostate cancer; prostate-specific antigen doubling time; mortality; surrogate endpoint ID RADICAL PROSTATECTOMY; RECURRENCE; MORTALITY; FAILURE; DEATH; RISK AB (Purpose:) under bar We evaluated whether posttreatment prostatic-specific antigen doubling time (PSADT) was predictive of prostate cancer mortality by testing the Prentice requirements for a surrogate endpoint. (Methods and Materials: ) under bar We analyzed posttreatment PSA measurements in a cohort of 1,514 men with localized prostate cancer (T2c-4 and PSA level < 150 ng/mL), treated and monitored prospectively on Radiation Therapy Oncology Group Protocol 92-02. From June 1992 to April 1995, men were randomized to neoadjuvant androgen deprivation and 65-70 Gy of radiation therapy (n = 761), or in combination with 24 months of adjuvant androgen deprivation (n = 753). Using an adjusted Cox proportional hazards model, we tested if PSADT was prognostic and independent of randomized treatment in this cohort. The endpoints were time to PSADT (assuming first-order kinetics for a minimum of 3 rising PSA measurements) and cancer-specific survival (CSS). (Results: ) under bar After a median follow-up time of 5.9 years, randomized treatment was a significant predictor for CSS (p(Cox) = 0.002), PSADT < 6 months (pc. < 0.001), PSADT < 9 months (P-Cox < 0.001), and PSADT < 12 months (P-Cox < 0.001) but not for PSADT < 3 (P-Cox = 0.4). The significant posttreatment PSADTs were also significant predictors of CSS (P-Cox < 0.001). After adjusting for T stage, Gleason score and PSA, all of Prentice's requirements were not met, indicating that the effect of PSADT on CSS was not independent of the randomized treatment. (Conclusions) under bar Prostatic specific antigen doubling time is significantly associated with CSS, but did not meet all of Prentice's requirements for a surrogate endpoint of CSS. Thus, the risk of dying of prostate cancer is not fully explained by PSADT. (c) 2006 Elsevier Inc. C1 Thomas Jefferson Univ, Dept Radiat Oncol, Philadelphia, PA 19107 USA. Amer Coll Radiol, Dept Radiat Oncol, Philadelphia, PA USA. Fox Chase Canc Ctr, Dept Radiat Oncol, Philadelphia, PA 19111 USA. Detroit Med Ctr, Dept Radiat Oncol, Detroit, MI USA. Mercy Hosp, Dept Radiat Oncol, Scranton, PA USA. Radiol Associates Sacramento, Sacramento, CA USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Univ Michigan, Ann Arbor, MI 48109 USA. RP Valicenti, RK (reprint author), Thomas Jefferson Univ Hosp, Dept Radiat Oncol, Bodine Ctr Canc Treatment, 111 S 11th St, Philadelphia, PA 19107 USA. EM Richard.Valicenti@mail.tju.edu FU NCI NIH HHS [CA-32115, CA-21661] NR 17 TC 33 Z9 34 U1 0 U2 0 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 NOV 15 PY 2006 VL 66 IS 4 BP 1064 EP 1071 DI 10.1016/j.ijrobp.2006.06.017 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 099MI UT WOS:000241598600015 PM 16979837 ER PT J AU Patel, S Jagsi, R Wilson, J Frank, S Thakkar, VV Hansen, EK AF Patel, Shilpen Jagsi, Reshma Wilson, John Frank, Steven Thakkar, Vipul V. Hansen, Eric K. TI Results of the 2004 Association of Residents in Radiation Oncology (ARRO) survey SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE Association of Residents in Radiation Oncology (ARRO); resident training; radiation oncology residency; graduate medical education; survey AB Purpose: The aim of this study was to document adequacy of training, career plans after residency, use of the in-service examination, and motivation for choice of radiation oncology as a specialty. Methods and Materials: In 2004, the Association of Residents in Radiation Oncology (ARRO) conducted a nationwide survey of all radiation oncology residents in the United States. Results: The survey was returned by 297 residents (response rate, 54%). Of the respondents, 29% were female and 71% male. The most popular career choice was joining an established private practice (38%), followed by a permanent academic career (29%). Residents for whom a permanent academic career was not their first choice were asked whether improvements in certain areas would have led them to be more likely to pursue an academic career. The most commonly chosen factors that would have had a strong or moderate influence included higher salary (81%), choice of geographic location (76%), faculty encouragement (68%), and less time commitment (68%). Of respondents in the first 3 years of training, 78% believed that they had received adequate training to proceed to the next level of training. Of those in their fourth year of training, 75% believed that they had received adequate training to enter practice. Conclusions: Multiple factors affect the educational environment of physicians in training. Data describing concerns unique to resident physicians in radiation oncology are limited. The current survey was designed to explore a variety of issues confronting radiation oncology residents. Training programs and the Residency Review Committee should consider these results when developing new policies to improve the educational experiences of residents in radiation oncology. (c) 2006 Elsevier Inc. C1 Univ Maryland, Med Ctr, Dept Radiat Oncol, Baltimore, MD 21201 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Penn, Philadelphia, PA 19104 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Cleveland Clin, Cleveland, OH 44106 USA. RP Patel, S (reprint author), Univ Maryland, Med Ctr, Dept Radiat Oncol, 22 S Greene St, Baltimore, MD 21201 USA. EM spatel@umm.edu OI Jagsi, Reshma/0000-0001-6562-1228 NR 13 TC 18 Z9 18 U1 0 U2 0 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 NOV 15 PY 2006 VL 66 IS 4 BP 1199 EP 1203 DI 10.1016/j.ijrobp.2006.06.024 PG 5 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 099MI UT WOS:000241598600032 PM 16979833 ER PT J AU Walter, LC Bertenthal, D Lindquist, K Konety, BR AF Walter, Louise C. Bertenthal, Daniel Lindquist, Karla Konety, Badrinath R. TI PSA screening among elderly men with limited life expectancies SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID LOCALIZED PROSTATE-CANCER; COMORBIDITY INDEX; UNITED-STATES; VIEWPOINT; VALIDATION; GUIDELINES; ACCURACY; CARE AB Context Most guidelines do not recommend prostate-specific antigen (PSA) screening in elderly men who have limited life expectancies because the known harms of screening outweigh potential benefits. However, there are no large-scale studies of actual PSA screening practices in elderly men, according to life expectancy. Objective To characterize the extent of PSA screening among elderly men, including those with limited life expectancies. Design, Setting, and Participants Cohort study of 597 642 male veterans aged 70 years and older who were seen at 104 US Department of Veterans Affairs facilities during both 2002 and 2003, without a history of prostate cancer, elevated PSA, or prostate cancer symptoms. Charlson comorbidity scores were used to stratify men into 3 groups ranging from best health ( score= 0) to worst health ( score >= 4). Main Outcome Measure Receipt of PSA testing during 2003 was based on US Department of Veterans Affairs data and Medicare claims. Results In 2003, 56% of elderly men had a PSA test performed. Although PSA screening rates decreased with advancing age, within each 5-year age group the percentage of men who underwent a PSA test did not substantially decline with worsening health. For example, among men aged 85 years and older, 34% in best health had a PSA test compared with 36% in worst health. In multivariate analyses, many nonclinical factors, such as marital status and region of the country, had a greater effect on PSA screening than health, and screening rates exceeded 60% for some subgroups of men in worst health. Conclusions Prostate-specific antigen screening rates among elderly veterans with limited life expectancies should be much lower than current practice given the known harms of screening. More attention to prognosis is needed when making screening PSA recommendations to elderly men. C1 San Francisco VA Med Ctr, Div Geriatr, San Francisco, CA USA. Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. San Francisco VA Med Ctr, Res Enhancement Award Program Improve Care Older, San Francisco, CA USA. Univ Calif San Francisco, Dept Urol, San Francisco, CA 94143 USA. RP Walter, LC (reprint author), VA Med Ctr, 181G,4150 Clement St, San Francisco, CA 94121 USA. EM louise.walter@ucsf.edu NR 47 TC 161 Z9 163 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 15 PY 2006 VL 296 IS 19 BP 2336 EP 2342 DI 10.1001/jama.296.19.2336 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 104ZI UT WOS:000241998700021 PM 17105796 ER PT J AU Falcone, S Cocucci, E Podini, P Kirchhausen, T Clementi, E Meldolesi, J AF Falcone, Sestina Cocucci, Emanuele Podini, Paola Kirchhausen, Tomas Clementi, Emilio Meldolesi, Jacopo TI Macropinocytosis: regulated coordination of endocytic and exocytic membrane traffic events SO JOURNAL OF CELL SCIENCE LA English DT Article DE macropinocytosis; regulated exocytosis; membrane traffic; dendritic cells; enlargeosomes ID HUMAN DENDRITIC CELLS; PHOSPHOINOSITIDE 3-KINASE; CONSTITUTIVE MACROPINOCYTOSIS; TRANSFORMED FIBROBLASTS; FOCAL EXOCYTOSIS; DOWN-REGULATION; NITRIC-OXIDE; A431 CELLS; RECEPTOR; MACROPHAGES AB Macropinocytosis, a form of bulk uptake of fluid and solid cargo into cytoplasmic vacuoles, called macropinosomes, has been studied mostly in relation to antigen presentation. Early membrane traffic events occurring in this process are, however, largely unknown. Using human dendritic cells we show that a marked increase in the rate of macropinocytosis occurs a few minutes after application of two markers ( small latex beads or dextran), depends on a slow intracellular Ca2(+) concentration ([Ca2+](i)) rise that precedes the PI3K-dependent step, and is preceded and accompanied by exocytosis of enlargeosomes compensating in part for the macropinocytic plasma membrane internalization. Unexpectedly, macropinosomes themselves, which share markers with endosomes, undergo Ca2+-dependent exocytosis so that, after similar to 20 minutes of continuous bead or dextran uptake, an equilibrium is reached preventing cells from overloading themselves with the organelles. Large [ Ca2+](i) increases induced by ionomycin trigger rapid (< 1 minute) exocytic regurgitation of all macropinosomes, whereas endosomes remain apparently unaffected. We conclude that, in dendritic cells, the rate of macropinocytosis is not constant but increases in a regulated fashion, as previously shown in other cell types. Moreover, macropinosomes are not simple containers that funnel cargo to an endocytic pathway, but unique organelles, distinct from endosomes by their competence for regulated exocytosis and other membrane properties. C1 Ist Sci San Raffaele, Stem Cell Res Inst, I-20132 Milan, Italy. E Medea Sci Inst, I-23842 Bosisio Parini, Italy. Univ Milan, Dept Preclin Sci, I-20157 Milan, Italy. Vita Salute San Raffale Univ, Ctr Excellence Cell Dev, Dept Neurosci, I-20132 Milan, Italy. Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. IIT Res Unit Mol Neurosci, I-20132 Milan, Italy. RP Meldolesi, J (reprint author), Ist Sci San Raffaele, Stem Cell Res Inst, Via Olgettina 58, I-20132 Milan, Italy. EM meldolesi.jacopo@hsr.it RI Falcone, Sestina/F-6103-2014 OI Falcone, Sestina/0000-0002-3574-0602 FU Telethon [GGP030234] NR 57 TC 117 Z9 118 U1 2 U2 16 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD NOV 15 PY 2006 VL 119 IS 22 BP 4758 EP 4769 DI 10.1242/jcs.03238 PG 12 WC Cell Biology SC Cell Biology GA 103NK UT WOS:000241893400019 PM 17077125 ER PT J AU Campanella, GSV Grimm, J Manice, LA Colvin, RA Medoff, BD Wojtkiewicz, GR Weissleder, R Luster, AD AF Campanella, Gabriele S. V. Grimm, Jan Manice, Lindsay A. Colvin, Richard A. Medoff, Benjamin D. Wojtkiewicz, Gregory R. Weissleder, Ralph Luster, Andrew D. TI Oligomerization of CXCL10 is necessary for endothelial cell presentation and in vivo activity SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MONOCYTE CHEMOATTRACTANT PROTEIN-3; IFN-INDUCIBLE PROTEIN-10; DIFFERENTIAL EXPRESSION; GLYCOSAMINOGLYCAN-BINDING; ALPHA-CHEMOATTRACTANT; ALLOGRAFT-REJECTION; CHEMOKINE RECEPTORS; MULTIPLE-SCLEROSIS; HEPARIN-BINDING; T-CELLS AB The chemokine IFN-gamma-inducible protein of 10 kDa (IP-10; CXCL10) plays an important role in the recruitment of activated T lymphocytes into sites of inflammation by interacting with the G protein-coupled receptor CXCR3. IP-10, like other chemokines, forms oligomers, the role of which has not yet been explored. In this study, we used a monomeric IP-10 mutant to elucidate the functional significance of oligomerization. Although monomeric IP-10 had reduced binding affinity for CXCR3 and heparin, it was able to induce in vitro chemotaxis of activated T cells with the same efficacy as wild-type IP-10. However, monomeric IP-10 was unable to induce recruitment of activated CD8(+) T cells into the airways of mice after intratracheal instillation. Use of a different IP-10 mutant demonstrated that this inability was due to lack of oligomerization rather than reduced CXCR3 or heparin binding. Molecular imaging demonstrated that both wild-type and monomeric IP-10 were retained in the lung after intratracheal instillation. However, in vitro binding assays indicated that wild-type, but not monomeric, IP-10 was retained on endothelial cells and could induce transendothelial chemotaxis of activated T cells. We therefore propose that oligomerization of IP-10 is required for presentation on endothelial cells and subsequent transendothelial migration, an essential step for lymphocyte recruitment in vivo. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol,Ctr Immunol & Inf, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. RP Luster, AD (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol,Ctr Immunol & Inf, Bldg 149,13th St, Charlestown, MA 02129 USA. EM luster.andrew@mgh.harvard.edu RI Grimm, Jan/B-1937-2008 FU NCI NIH HHS [R24-CA92782, R01-CA69212] NR 41 TC 57 Z9 59 U1 0 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 15 PY 2006 VL 177 IS 10 BP 6991 EP 6998 PG 8 WC Immunology SC Immunology GA 105DN UT WOS:000242009700049 PM 17082614 ER PT J AU Atkinson, C Zhu, H Qiao, F Varela, JC Yu, J Song, HB Kindy, MS Tomlinson, S AF Atkinson, Carl Zhu, Hong Qiao, Fei Varela, Juan Carlos Yu, Jin Song, Hongbin Kindy, Mark S. Tomlinson, Stephen TI Complement-dependent P-selectin expression and injury following ischemic stroke SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MIDDLE CEREBRAL-ARTERY; RENAL ISCHEMIA/REPERFUSION INJURY; BRAIN-INJURY; REPERFUSION INJURY; MONOCLONAL-ANTIBODY; INHIBITORY PROTEIN; MICE DEFICIENT; MURINE STROKE; TISSUE-INJURY; C1 INHIBITOR AB The mechanisms that contribute to inflammatory damage following ischemic stroke are poorly characterized, but studies indicate a role for both complement and P-selectin. In this study, we show that compared with wild-type mice, C3-deficient mice showed significant improvement in survival, neurological deficit, and infarct size at 24 h after middle cerebral artery occlusion and reperfusion. Furthermore, P-selectin protein expression was undetectable in the cerebral microvasculature of C3-deficient mice following reperfusion, and there was reduced neutrophil influx, reduced microthrombus formation, and increased blood flow postreperfusion in C3-deficient mice. We further investigated the use of a novel complement inhibitory protein in a therapeutic paradigm. Complement receptor 2 (CR2)-Crry inhibits complement activation at the C3 stage and targets to sites of complement activation. Treatment of normal mice with CR2-Crry at 30 min postreperfusion resulted in a similar level of protection to that seen in C3-deficient mice in all of the above-measured parameters. The data demonstrate an important role for complement in cerebrovascular thrombosis, inflammation, and injury following ischemic stroke. P-selectin expression in the cerebrovasculature, which is also implicated in cerebral ischemia and reperfusion injury, was shown to be distal to and dependent on complement activation. Data also show that a CR2-targeted approach of complement inhibition provides appropriate bioavailability in cerebral injury to enable complement inhibition at a dose that does not significantly affect systemic levels of serum complement activity, a potential benefit for stroke patients where immunosuppression would be undesirable due to significantly increased susceptibility to lung infection. C1 Med Univ S Carolina, Dept Microbiol & Immunol, Childrens Res Inst, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Neurosci, Inst Neurosci, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29425 USA. RP Tomlinson, S (reprint author), Med Univ S Carolina, Dept Microbiol & Immunol, Childrens Res Inst, Charleston, SC 29425 USA. EM tomlinss@musc.edu RI Song, Hongbin/C-1963-2013 FU NHLBI NIH HHS [HL082485] NR 55 TC 48 Z9 52 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 15 PY 2006 VL 177 IS 10 BP 7266 EP 7274 PG 9 WC Immunology SC Immunology GA 105DN UT WOS:000242009700080 PM 17082645 ER PT J AU Martin, AP Canasto-Chibuque, C Shang, LM Rollins, BJ Lira, SA AF Martin, Andrea P. Canasto-Chibuque, Claudia Shang, Limin Rollins, Barrett J. Lira, Sergio A. TI The chemokine decoy receptor M3 blocks CC chemokine ligand 2 and CXC chemokine ligand 13 function in vivo SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MURINE GAMMAHERPESVIRUS 68; MONOCYTE CHEMOATTRACTANT PROTEIN-1; BINDING-PROTEIN; PANCREATIC-ISLETS; CELL RECRUITMENT; DIFFERENTIAL EXPRESSION; MULTIPLE-SCLEROSIS; B-CELLS; HERPESVIRUS; IDENTIFICATION AB Chemokines and their receptors play a key role in immune homeostasis regulating leukocyte migration, differentiation, and function. Viruses have acquired and optimized molecules that interact with the chemokine system. These virus-encoded molecules promote cell entry, facilitate dissemination of infected cells, and enable the virus to evade the immune response. One such molecule in the murine gammaherpesvirus 68 genome is the M3 gene, which encodes a secreted 44-kDa protein that binds with high affinity to certain murine and human chemokines and blocks chemokine signaling in vitro. To test the hypothesis that M3 directly interferes with diverse chemokines in vivo, we examined the interaction of M3 with CCL2 and CXCL13 expressed in the pancreas of transgenic mice. CCL2 expression in the pancreas promoted recruitment of monocytes and dendritic cells; CXCL13 promoted recruitment of B and T lymphocytes. Coexpression of M3 in the pancreas blocked cellular recruitment induced by both CCL2 and CXCL13. These results define M3 as multichemokine blocker and demonstrate its use as a powerful tool to analyze chemokine biology. C1 CUNY Mt Sinai Sch Med, Immunobiol Ctr, New York, NY 10029 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Lira, SA (reprint author), CUNY Mt Sinai Sch Med, Immunobiol Ctr, 1425 Madison Ave,Box 1630, New York, NY 10029 USA. EM sergio.lira@mssm.edu FU NIDDK NIH HHS [DK067381] NR 42 TC 33 Z9 33 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 15 PY 2006 VL 177 IS 10 BP 7296 EP 7302 PG 7 WC Immunology SC Immunology GA 105DN UT WOS:000242009700083 PM 17082648 ER PT J AU Sekine, H Graham, KL Zhao, SR Elliott, MK Ruiz, P Utz, PJ Gilkeson, GS AF Sekine, Hideharu Graham, Kareem L. Zhao, Shenru Elliott, Margaret K. Ruiz, Philip Utz, Paul J. Gilkeson, Gary S. TI Role of MHC-linked genes in autoantigen selection and renal disease in a murine model of systemic lupus erythematosus SO JOURNAL OF IMMUNOLOGY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; MRL/LPR MICE; LPR MICE; ANTI-SM; RHEUMATOID-FACTOR; IGA DEFICIENCY; LPR/LPR MICE; MRL MICE; GLOMERULONEPHRITIS; AUTOANTIBODIES AB We previously described a renal protective effect of factor B deficiency in MRL/lpr mice. Factor B is in the MHC cluster; thus, the deficient mice were H2(b), the haplotype on which the knockout was derived, whereas the wild-type littermates were H2(k), the H2 of MRL/lpr mice. To determine which protective effects were due to H2 vs factor B deficiency, we derived H2(b) congenic MRL/lpr mice from the 129/Sv (H2(b)) strain. Autoantibody profiling using autoantigen microarrays revealed that serum anti-Smith and anti-small nuclear ribonucleoprotein complex autoantibodies, while present in the majority of H2(k/k) MRL/lpr mice, were absent in the H2(b/b) MRL/lpr mice. Surprisingly, 70% of MRL/lpr H2(b/b) mice were found to be serum IgG3 deficient (with few to no IgG3-producing B cells). In addition, H2(b/b) IgG3-deficient MRL/lpr mice had significantly less proteinuria, decreased glomerular immune complex deposition, and absence of glomerular subepithelial deposits compared with MRL/lpr mice of any H2 type with detectable serum IgG3. Despite these differences, total histopathologic renal scores and survival were similar among the groups. These results indicate that genes encoded within or closely linked to the MHC region regulate autoantigen selection and isotype switching to IgG3 but have minimal effect on end-organ damage or survival in MRL/lpr mice. C1 Med Univ S Carolina, Dept Med, Div Rheumatol & Immunol, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Med Res Serv, Charleston, SC 29425 USA. Stanford Univ, Sch Med, Dept Med, Div Rheumatol & Immunol, Stanford, CA 94305 USA. Univ Miami, Sch Med, Dept Pathol, Miami, FL 33125 USA. RP Sekine, H (reprint author), 96 Jonathon Lucas St,Suite 912,POB 250637, Charleston, SC 29425 USA. EM sekineh@muse.edu FU NIAID NIH HHS [AI01514, AI10663, T32 AI007290, AI47469, AI50864]; NIAMS NIH HHS [AR49328]; NIDDK NIH HHS [DK61934] NR 62 TC 20 Z9 21 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 15 PY 2006 VL 177 IS 10 BP 7423 EP 7434 PG 12 WC Immunology SC Immunology GA 105DN UT WOS:000242009700097 PM 17082662 ER PT J AU Ma, ZJ Chen, FQ Madaio, MP Cohen, PL Eisenberg, RA AF Ma, Zhongjie Chen, Fangqi Madaio, Michael P. Cohen, Philip L. Eisenberg, Robert A. TI Modulation of autoimmunity by TLR9 in the chronic graft-vs-host model of systemic lupus erythematosus SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TOLL-LIKE RECEPTORS; B-CELLS; INNATE IMMUNITY; MURINE LUPUS; VERSUS-HOST; DNA; AUTOANTIBODIES; SLE; DISEASE; MICE AB Chronic graft-vs-host (cGVH) disease is induced in nonautoimmune mice by the transfer of alloreactive T cells that recognize foreign MHC class II. It closely resembles. systemic lupus erythematosus, with antinuclear Abs and immune-mediated nephritis. Recent work has implicated TLRs, particularly TLR9, in the recognition of certain autoantigens in vitro and in vivo. To explore further the role of TLR9 in systemic autoimmunity, we induced cGVH disease in C57BL/6 (1116) mice lacking TLR9, including B6 mice expressing the anti-DNA-encoding IgH transgenes; 3119 or 56R (B6.3H9.TLR9(-/-), B6.56R.TLR9(-/-)). We found that cGVH disease caused breakdown of B cell tolerance to chromatin and DNA in TLR9(-/-) recipients of alloreactive cells, yet that nephritis was less severe and that some autoantibody titers were lower compared with B6-cGVH controls. Spleen lymphocyte analysis showed that cGVH disease strikingly depleted marginal zone B cells in B6 mice, but did not influence T cell subsets in either B6 or B6-TLR9(-/-) hosts. B6.56R.TLR9(-/-) mice had less spontaneous production of autoantibodies than B6.56R mice, but there were no significant differences between B6.56R and B6.56R.TLR9(-/-) postinduction of cGVH disease. Taken together, these results suggested that TLR9 may worsen some aspects of systemic autoimmunity while alleviating others. C1 Univ Penn, Div Rheumatol, Philadelphia, PA 19104 USA. Univ Penn, Div Renal Electrolyte & Hypertens, Dept Med, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. RP Eisenberg, RA (reprint author), Univ Penn, Div Rheumatol, 756 BRB2 3,421 Curie Blvd, Philadelphia, PA 19104 USA. EM raemd@mail.med.upenn.edu FU NIAID NIH HHS [R01-AI063626-22, U19-AI-46358]; NIAMS NIH HHS [R01-AR-34156]; NIDDK NIH HHS [R01-DK53088] NR 25 TC 11 Z9 14 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 15 PY 2006 VL 177 IS 10 BP 7444 EP 7450 PG 7 WC Immunology SC Immunology GA 105DN UT WOS:000242009700099 PM 17082664 ER PT J AU Xie, AL Skatrud, JB Morgan, B Chenuel, B Khayat, R Reichmuth, K Lin, J Dempsey, JA AF Xie, Ailiang Skatrud, James B. Morgan, Barbara Chenuel, Bruno Khayat, Rami Reichmuth, Kevin Lin, Jenny Dempsey, Jerome A. TI Influence of cerebrovascular function on the hypercapnic ventilatory response in healthy humans SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID CEREBRAL-BLOOD-FLOW; CONGESTIVE-HEART-FAILURE; CAROTID-BODY DENERVATION; CENTRAL SLEEP-APNEA; CARBON-DIOXIDE; NEWBORN PIGLETS; ASPHYXIATED PIGLETS; QUANTITATIVE EEG; GRADED REDUCTION; CO2 REACTIVITY AB An important determinant of [H+] in the environment of the central chemoreceptors is cerebral blood flow. Accordingly we hypothesized that a reduction of brain perfusion or a reduced cerebrovascular reactivity to CO2 would lead to hyperventilation and an increased ventilatory responsiveness to CO2. We used oral indomethacin to reduce the cerebrovascular reactivity to CO2 and tested the steady-state hypercapnic ventilatory response to CO2 in nine normal awake human subjects under normoxia and hyperoxia (50% O-2). Ninety minutes after indomethacin ingestion, cerebral blood flow velocity (CBFV) in the middle cerebral artery decreased to 77 +/- 5% of the initial value and the average slope of CBFV response to hypercapnia was reduced to 31% of control in normoxia (1.92 versus 0.59 cm(-1) s(-1) mmHg(-1), P < 0.05) and 37% of control in hyperoxia (1.58 versus 0.59 cm(-1) s(-1) mmHg(-1), P < 0.05). Concomitantly, indomethacin administration also caused 40-60% increases in the slope of the mean ventilatory response to CO2 in both normoxia (1.27 +/- 0.31 versus 1.76 +/- 0.37 l min(-1) mmHg(-1), P < 0.05) and hyperoxia (1.08 +/- 0.22 versus 1.79 +/- 0.37 l min(-1) mmHg(-1), P < 0.05). These correlative findings are consistent with the conclusion that cerebrovascular responsiveness to CO2 is an important determinant of eupnoeic ventilation and of hypercapnic ventilatory responsiveness in humans, primarily via its effects at the level of the central chemoreceptors. C1 William S Middleton Mem Vet Adm Med Ctr, Pulm Physiol Lab, Madison, WI 53705 USA. Univ Wisconsin, Dept Med, Madison, WI 53706 USA. Univ Wisconsin, Dept Populat Hlth Sci, Madison, WI 53706 USA. Univ Wisconsin, Dept Orthopeid & Rehabil, Madison, WI 53706 USA. RP Xie, AL (reprint author), William S Middleton Mem Vet Adm Med Ctr, Pulm Physiol Lab, 2500 Overlook Terrace, Madison, WI 53705 USA. EM axie@facstaff.wisc.edu RI Khayat, Rami/E-3380-2011 NR 68 TC 70 Z9 70 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD NOV 15 PY 2006 VL 577 IS 1 BP 319 EP 329 DI 10.1113/jphysiol.2006.110627 PG 11 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 108LC UT WOS:000242240300025 PM 16931556 ER PT J AU McGory, ML Shekelle, PG Ko, CY AF McGory, Marcia L. Shekelle, Paul G. Ko, Clifford Y. TI Development of quality indicators for patients undergoing colorectal cancer surgery SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID CORONARY REVASCULARIZATION; PRACTICE PARAMETERS; VULNERABLE ELDERS; ASSESSING CARE; COLON-CANCER; OF-CARE; APPROPRIATENESS; UNDERUSE; PROGRAM; RATINGS AB Background. Colorectal cancer is the second most common cancer type among new cancer diagnoses in the United States. Attention to the quality of surgical care for colorectal cancer is of particular importance given the increasing numbers of colorectal cancer resections performed in the aging population. A National Cancer Institute-sponsored consensus panel produced guidelines for colorectal cancer surgery in 2000. We have updated and extended that work by using a formal process to identify and rate quality indicators as valid for care during the preoperative, intraoperative, and postoperative periods. Methods: Using a modification of the RAND/UCLA Appropriateness Methodology, we carried out structured interviews with leaders in the field of colorectal cancer surgery and systematic reviews of the literature to identify candidate quality indicators addressing perioperative care for patients undergoing surgery for colorectal cancer. A panel of 14 colorectal surgeons, general surgeons, and surgical oncologists then evaluated and formally rated the indicators using the modified Delphi method to identify valid indicators. Results: A total of 142 candidate indicators were identified in six broad domains: privileging (which addresses surgical credentials), preoperative evaluation, patient-provider discussions, medication use, intraoperative care, and postoperative management. The expert panel rated 92 indicators as valid. These indicators address all domains of perioperative care for patients undergoing surgery for colorectal cancer. Conclusions: The RAND/UCLA Appropriateness Methodology can be used to identify and rate indicators of high-quality perioperative care for patients undergoing surgery for colorectal cancer. The indicators can be used as quality performance measures and for quality-improvement programs. C1 Univ Calif Los Angeles, Dept Surg, David Geffen Sch Med, Ctr Hlth Sci,Ctr Surg Outcomes & Qual, Los Angeles, CA 90095 USA. VA Greater Los Angeles Healthcare Syst, Dept Med, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Dept Surg, Los Angeles, CA USA. RP McGory, ML (reprint author), Univ Calif Los Angeles, Dept Surg, David Geffen Sch Med, Ctr Hlth Sci,Ctr Surg Outcomes & Qual, 10833 Conte Ave,72-215,Box 956904, Los Angeles, CA 90095 USA. EM mmcgory@mednet.ucla.edu NR 28 TC 76 Z9 78 U1 0 U2 1 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 NOV 15 PY 2006 VL 98 IS 22 BP 1623 EP 1633 DI 10.1093/jnci/djj438 PG 11 WC Oncology SC Oncology GA 110LF UT WOS:000242379700009 PM 17105985 ER PT J AU Stone, ME AF Stone, Martha E. TI When illness goes public: Celebrity patients and how we look at medicine. SO LIBRARY JOURNAL LA English DT Book Review C1 Massachusetts Gen Hosp, Lib, Boston, MA 02114 USA. RP Stone, ME (reprint author), Massachusetts Gen Hosp, Lib, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 1 PU REED BUSINESS INFORMATION PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010 USA SN 0363-0277 J9 LIBR J JI Libr. J. PD NOV 15 PY 2006 VL 131 IS 19 BP 88 EP 89 PG 2 WC Information Science & Library Science SC Information Science & Library Science GA 109QH UT WOS:000242323000229 ER PT J AU Ciesielski, KT Lesnik, PG Savoy, RL Grant, EP Ahlfors, SP AF Ciesielski, Kristina T. Lesnik, Paul G. Savoy, Robert L. Grant, Ellen P. Ahlfors, Seppo P. TI Developmental neural networks in children performing a Categorical n-back task SO NEUROIMAGE LA English DT Review DE development of neural networks; visual working memory with categorization; ventral and dorsal visual streams; cortical/striatal/cerebellar network; event-related fMRI ID SPATIAL WORKING-MEMORY; POSITRON EMISSION TOMOGRAPHY; COMMON STEREOTACTIC SPACE; HUMAN VISUAL-CORTEX; PREFRONTAL CORTEX; FUNCTIONAL MRI; BASAL GANGLIA; COGNITIVE-DEVELOPMENT; BRAIN-DEVELOPMENT; LEVEL CATEGORIES AB The prefrontal and temporal networks subserving object working memory tasks in adults have been reported as immature in young children; yet children are adequately capable of performing such tasks. We investigated the basis of this apparent contradiction using a complex object working memory task, a Categorical n-back (CN-BT). We examined whether the neural networks engaged by the CN-BT in children consist of the same brain regions as those in adults, but with a different magnitude of activation, or whether the networks are qualitatively different. Event-related fMRI was used to study differences in brain activation between healthy children ages 6 and 10 years, and young adults (20-28 years). Performance accuracy and RTs in 10-year-olds and adults were comparable, but the performance in 6-year-olds was lower. In adults, the CN-BT was highly effective in engaging the bilateral (L > R) ventral prefrontal cortex, the bilateral fusiform gyrus, posterior cingulate and precuneus, thus suggesting an involvement of the ventral visual stream, with related feature extraction and semantic labeling strategies. In children, the brain networks were distinctly different. They involved the premotor and parietal cortex, anterior insula, caudate/putamen, and the cerebellum, thus suggesting a predominant involvement of the visual dorsal and sensory-motor pathways, with related visual-spatial and action cognitive strategies. The findings indicate engagement of develop-mental networks in children reflecting task-effective brain activation. The age-related pattern of fMRI activation suggests a working hypothesis of a developmental shift from reliance on the dorsal visual stream and premotor/striatal/cerebellar networks in young children to reliance on the ventral prefrontal and inferior temporal networks in adults. (c) 2006 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging,MIT, Charlestown, MA 02129 USA. Univ New Mexico, Dept Psychol, Albuquerque, NM 87131 USA. Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02120 USA. RP Ciesielski, KT (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging,MIT, 149 13th St, Charlestown, MA 02129 USA. EM ktc@nmr.mgh.harvard.edu RI Ahlfors, Seppo/P-3644-2016 FU NCRR NIH HHS [P41RR14075] NR 110 TC 67 Z9 75 U1 6 U2 17 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD NOV 15 PY 2006 VL 33 IS 3 BP 980 EP 990 DI 10.1016/j.neuroimage.2006.07.028 PG 11 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 101RW UT WOS:000241759200017 PM 16997580 ER PT J AU Buhlmann, U Deckersbach, T Engelhard, I Cook, LM Rauch, SL Kathmann, N Wilhelm, S Savage, CR AF Buhlmann, Ulrike Deckersbach, Thilo Engelhard, Iris Cook, Laura M. Rauch, Scott L. Kathmann, Norbert Wilhelm, Sabine Savage, Cary R. TI Cognitive retraining for organizational impairment in obsessive-compulsive disorder SO PSYCHIATRY RESEARCH LA English DT Article DE obsessive-compulsive disorder; neuropsychology; nonverbal memory; organization; recall; Rey-Osterrieth Complex Figure; Taylor Complex Figure ID VERBAL-LEARNING STRATEGIES; NONVERBAL MEMORY; DIRECTED APPLICATION; PERFORMANCE; CORTEX; PET AB Individuals with obsess ive-compulsive disorder (OCD) have difficulties in organizing information during encoding associated with subsequent memory impairments. This study was designed to investigate whether impairments in organization in individuals with OCD can be alleviated with cognitive training. Thirty-five OCD subjects and 36 controls copied and recalled the Rey-Osterrieth Complex Figure Test (RCFT) [Osterrieth, P.A., 1944. Le test de copie d'une figure complexe: Contribution a l'etude de la perception et de la memoire (The test of copying a complex figure: A contribution to the study of perception and memory). Archive de Psychologie 30, 286-350.] before being randomly assigned to a training or non-training condition. The training condition was designed to improve the ability to organize complex visuospatial information in a meaningful way. The intervention phase was followed by another copy and recall trial of the RCFT. Both OCD and control subjects who underwent training improved more in organization and memory than subjects who did not receive organizational training, providing evidence that the training procedure was effective. OCD subjects improved more in organizational during encoding than control subjects, irrespective of whether or not they had received training. This suggests that organization impairment in OCD affects primarily the ability to spontaneously utilize strategies when faced with complex, ambiguous information but that the ability to implement such strategies when provided with additional trials is preserved. These findings support a distinction in OCD between failure to utilize a strategy and incapacity to implement a strategy. (c) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat,OCD Clin, Boston, MA 02114 USA. Univ Utrecht, Dept Clin Psychol, Utrecht, Netherlands. Humboldt Univ, Dept Clin Psychol, Berlin, Germany. Univ Kansas, Med Ctr, Hoglund Brain Imaging Ctr, Kansas City, KS 66103 USA. Univ Kansas, Med Ctr, Dept Psychiat & Behav Sci, Kansas City, KS 66103 USA. RP Buhlmann, U (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat,OCD Clin, 185 Cambridge St, Boston, MA 02114 USA. EM buhlmann@psych.mgh.harvard.edu NR 38 TC 39 Z9 40 U1 7 U2 17 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD NOV 15 PY 2006 VL 144 IS 2-3 BP 109 EP 116 DI 10.1016/j.psychres.2006.10.012 PG 8 WC Psychiatry SC Psychiatry GA 114NT UT WOS:000242673600002 PM 17007938 ER PT J AU Ishiguro, K Ando, T Maeda, O Hasegawa, M Kadomatsu, K Ohmiya, N Niwa, Y Xavier, R Goto, H AF Ishiguro, Kazuhiro Ando, Takafumi Maeda, Osamu Hasegawa, Motofusa Kadomatsu, Kenji Ohmiya, Naoki Niwa, Yasumasa Xavier, Ramnik Goto, Hidemi TI Paeonol attenuates TNBS-induced colitis by inhibiting NF-kappa B and STAT1 transactivation SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE colitis; medical plants; TNF alpha; IFN type II; NF-kappa B; STAT1 transcription factor ID INFLAMMATORY-BOWEL-DISEASE; NITRIC-OXIDE SYNTHASE; MOUTAN CORTEX; PATHOGENESIS; ACTIVATION; APOPTOSIS; PROTEINS; BINDING; MICE AB Paeonol, a major phenolic component of Moutan Cortex, is known to have anti-inflammatory activity. However, the effect of Paeonol on colitis has not been evaluated and the molecular mechanism of its anti-inflammatory action remains unknown. The aim of this study was to determine if Paeonol enema attenuates trinitrobenzene sulfonic acid (TNBS)-induced colitis in mice. We also investigated the effects of Paeonol in colon cancer-derived CW-2 cells and T cell leukemia-derived Jurkat cells treated with tumor necrosis factor alpha (TNF alpha) and/or interferon gamma (IFN gamma), which play critical roles in TNBS-induced colitis. Paeonol enema attenuated TNBS-induced colitis judging by body weigh reduction, colon length and histological score. Myeloperoxidase activity and inducible nitric oxide synthase (iNOS) production in the colon were also reduced with Paeonol enema. In CW-2 cells, Paeonol inhibited NOS protein and mRNA expression induced by costimulation of TNF alpha and IFN gamma. Furthermore, Paeonol reduced TNF alpha-induced NF-kappa B transactivation and IFN-gamma-induced STAT1 transactivation in CW-2 cells and also in Jurkat cells. These findings suggest that Paeonol enema may be useful for the treatment of colitis. (c) 2006 Elsevier Inc. All rights reserved. C1 Nagoya Univ, Sch Med, Showa Ku, Nagoya, Aichi 4468550, Japan. Nagoya Univ, Grad Sch Med, Dept Gastroenterol, Nagoya, Aichi 4468550, Japan. Nagoya Univ, Grad Sch Med, Dept Biochem, Nagoya, Aichi 4468550, Japan. Massachusetts Gen Hosp, Ctr Computat & Integrat Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Ishiguro, K (reprint author), Nagoya Univ, Sch Med, Showa Ku, 65 Tsurumai Cho, Nagoya, Aichi 4468550, Japan. EM kio@med.nagoya-u.ac.jp RI Kadomatsu, Kenji/G-8083-2012; MAEDA, Osamu/Q-1016-2015; OI Ishiguro, Kazuhiro/0000-0003-1776-2805 NR 26 TC 40 Z9 43 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD NOV 15 PY 2006 VL 217 IS 1 BP 35 EP 42 DI 10.1016/j.taap.2006.07.002 PG 8 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 104DT UT WOS:000241937100005 PM 16928387 ER PT J AU Vlasak, J Ruprecht, RM AF Vlasak, Josef Ruprecht, Ruth M. TI AIDS vaccine development and challenge viruses: Getting real SO AIDS LA English DT Editorial Material ID HUMAN-IMMUNODEFICIENCY-VIRUS; T-CELL DEPLETION; PIG-TAILED MACAQUES; TYPE-1 SUBTYPE-C; RHESUS MACAQUES; IN-VIVO; GASTROINTESTINAL-TRACT; PERSISTENT INFECTION; IMMUNE-RESPONSES; SIV INFECTION C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ S Bohemia, Fac Biol Sci, Ceske Budejovice, Czech Republic. RP Ruprecht, RM (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM ruth_ruprecht@dfci.harvard.edu FU NIAID NIH HHS [P01 AI 48240, R37 AI 34266] NR 67 TC 21 Z9 21 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD NOV 14 PY 2006 VL 20 IS 17 BP 2135 EP 2140 DI 10.1097/QAD.0b013e328010beb5 PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 114PA UT WOS:000242676900001 PM 17086052 ER PT J AU Ulmer, S Braga, TA Barker, FG Lev, MH Gonzalez, RG Henson, JW AF Ulmer, S. Braga, T. A. Barker, F. G., II Lev, M. H. Gonzalez, R. G. Henson, J. W. TI Clinical and radiographic features of peritumoral infarction following resection of glioblastoma SO NEUROLOGY LA English DT Article; Proceedings Paper CT 55th Annual Meeting of the American-Academy-of-Neurology CY MAR 29-APR 05, 2003 CL HONOLULU, HI SP Amer Acad Neurol ID CEREBRAL WHITE-MATTER; MICROVASCULATURE; ARTERIES AB Focal areas of restricted diffusion adjacent to high-grade glioma resection cavities were detected in 70% of patients on immediate postoperative MRI studies. Follow-up studies demonstrated cystic encephalomalacia in 91% of these foci, suggesting the presence of infarction, and the infarcted tissue demonstrated enhancement in 43% of cases. New postoperative deficits correlated well with the anatomic region of infarction in six patients. Enhancement in perioperative infarcts can mimic tumor progression on follow-up imaging studies. C1 Massachusetts Gen Hosp, Stephen E Catherine Pappas Ctr Neurooncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Neuroradiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neurol Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Henson, JW (reprint author), Massachusetts Gen Hosp, Stephen E Catherine Pappas Ctr Neurooncol, Yawkey 9 E,55 Fruit St, Boston, MA 02114 USA. EM henson@helix.mgh.harvard.edu NR 6 TC 65 Z9 67 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD NOV 14 PY 2006 VL 67 IS 9 BP 1668 EP 1670 DI 10.1212/01.wnl.0000242894.21705.3c PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 104WN UT WOS:000241991400025 PM 17101902 ER PT J AU Pieretti-Vanmarcke, R Donahoe, PK Pearsall, LA Dinulescu, DM Connolly, DC Halpern, EF Seiden, MV MacLaughlin, DT AF Pieretti-Vanmarcke, Rafael Donahoe, Patricia K. Pearsall, Lisa A. Dinulescu, Daniela M. Connolly, Denise C. Halpern, Elkan F. Seiden, Michael V. MacLaughlin, David T. TI Mullerian inhibiting substance enhances subclinical doses of chemotherapeutic agents to inhibit human and mouse ovarian cancer SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE combination treatment; Mullerian inhibiting substance type II receptor ID ORGAN-CULTURE ASSAY; IN-VIVO; II RECEPTOR; BREAST-CANCER; DUCT REGRESSION; CELL-GROWTH; IMMUNOPHILIN FKBP12; EXPRESSION; PATHWAY; VITRO AB Mullerian Inhibiting Substance (MIS), a biological modifier that causes regression of Mullerian ducts in male embryos, is effective as a single agent in vitro and in vivo against human and mouse ovarian cancer cell lines expressing MIS type 11 receptor; however, little is known about how recombinant human MIS (rhMIS), now being scaled for preclinical trials, could be used in combination with cytotoxic or targeted chemotherapeutic agents. Mouse serous and endometrioid ovarian carcinoma cell lines were tested in vitro against rhMIS alone and with doxorubicin, paclitaxel, or cisplatin as agents in clinical use. Because MIS releases FK506 binding protein (FKBP12), which activates the mammalian target of rapamycin (mTOR) downstream of Akt, rhMIS and rapamycin combinations were tested. MIS increases p16 protein levels, and 5'-Aza2'-deoxycytidine (AzadC) induces p16 mRNA; therefore, they were used in combination in vitro and in vivo with a human ovarian cancer cell line. A paclitaxel-resistant human ovariain cancer cell line and its parental line both respond to rhMIS in vitro. Additivity, synergy, or competition was observed with MIS and rapamycin, AzadC, doxorubicin, cisplatin, and paclitaxel, suggesting that MIS in combination with selective targeted therapies might achieve greater activity against ovarian cancer than the use of each individual agent alone. These assays and statistical analyses could be useful in selecting rhMIS and chemotherapeutic agent combinations that enhance clinical efficacy and reduce toxicity. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Pediat Surg Res Labs, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Inst Technol & Assessment, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ovarian Tumor Biol Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol,Eugene Braunwald Res Ctr, Boston, MA 02115 USA. Fox Chase Canc Ctr, Div Med Sci, Philadelphia, PA 19111 USA. RP Donahoe, PK (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Pediat Surg Res Labs, CPZN6200,185 Cambridge St, Boston, MA 02114 USA. EM pdonahoe@partners.org; maclaugh@helix.mgh.harvard.edu FU NCI NIH HHS [1K24 CA109416, U01 CA084242, R01 CA017393, K24 CA109416, CA 17393, P50 CA083638]; NICHD NIH HHS [HD 32212] NR 63 TC 27 Z9 28 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 14 PY 2006 VL 103 IS 46 BP 17426 EP 17431 DI 10.1073/pnas.0607959103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 108OP UT WOS:000242249400065 PM 17088539 ER PT J AU Yamamoto-Furusho, JK Korzenik, JR AF Yamamoto-Furusho, Jesus K. Korzenik, Joshua R. TI Crohn's disease: Innate immunodeficiency? SO WORLD JOURNAL OF GASTROENTEROLOGY LA English DT Review DE Crohn's disease; innate immunity; immunodeficiency; NOD2 ID INFLAMMATORY-BOWEL-DISEASE; COLONY-STIMULATING FACTOR; INTESTINAL EPITHELIAL-CELLS; NF-KAPPA-B; PANETH CELLS; NOD2; NEUTROPHILS; DIPEPTIDE; NEUTROPENIA; EXPRESSION AB In the past, Crohn's disease (CD) has been understood primarily as an immunologic disorder characterized by an abnormal T-cell response. Recent in vitro and in vivo data suggests that CD may instead be precipitated by innate immune dysfunction resulting from a combination of genetic and environmental factors. Some reports have demonstrated a defective immune response in a variety of other cellular components, including neutrophils, monocytes and dendritic cells. Recent studies of granulocyte-macrophage colony-stimulating factor (GMCSF) in CD, aiming to stimulate the innate immune system with the conception that an innate immune defect underlies the development of the disease, have been demonstrated a clinical benefit and reinforce this evolving understanding of the disease. (C) 2006 The WJG Press. All rights reserved. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Yamamoto-Furusho, JK (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, 55 Fruit St, Boston, MA 02114 USA. EM kazuofurusho@hotmail.com NR 47 TC 24 Z9 24 U1 1 U2 2 PU W J G PRESS PI BEIJING PA PO BOX 2345, BEIJING 100023, PEOPLES R CHINA SN 1007-9327 J9 WORLD J GASTROENTERO JI World J. Gastroenterol. PD NOV 14 PY 2006 VL 12 IS 42 BP 6751 EP 6755 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 106MS UT WOS:000242105400003 PM 17106921 ER PT J AU Barzilay, JI Davis, BR Cutler, JA Pressel, SL Whelton, PK Basile, J Margolis, KL Ong, ST Sadler, LS Summerson, J AF Barzilay, Joshua I. Davis, Barry R. Cutler, Jeffrey A. Pressel, Sara L. Whelton, Paul K. Basile, Jan Margolis, Karen L. Ong, Stephen T. Sadler, Laurie S. Summerson, John CA ALLHAT Collaborative Res Grp TI Fasting glucose levels and incident diabetes mellitus in older nondiabetic adults randomized to receive 3 different classes of antihypertensive treatment - A report from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID ISOLATED SYSTOLIC HYPERTENSION; CARDIOVASCULAR EVENTS; THIAZIDE DIURETICS; THERAPY; RISK; OUTCOMES; INTOLERANCE; POTASSIUM; REDUCTION; INHIBITOR AB Background: Elevated blood glucose levels are reported with thiazide-type diuretic treatment of hypertension. The significance of this finding is uncertain. Our objectives were to compare the effect of first-step antihypertensive drug therapy with thiazide-type diuretic, calcium-channel blocker, or angiotensin-converting enzyme inhibitor on fasting glucose (FG) levels and to determine cardiovascular and renal disease risks associated with elevated FG levels and incident diabetes mellitus (DM) in 3 treatment groups. Methods: We performed post hoc subgroup analyses from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) among nondiabetic participants who were randomized to receive treatment with chlorthalidone (n= 8419), amlodipine (n= 4958), or lisinopril ( n= 5034) and observed for a mean of 4.9 years. Results: Mean FG levels increased during follow-up in all treatment groups. At year 2, those randomized to the chlorthalidone group had the greatest increase ( + 8.5 mg/dL [0.47 mmol/L] vs + 5.5 mg/dL [0.31 mmol/L] for amlodipine and + 3.5 mg/dL [0.19 mmol/L] for lisinopril). The odds ratios for developing DM with lisinopril (0.55 [95% confidence interval, 0.43-0.70]) or amlodipine (0.73 [ 95% confidence interval, 0.58-0.91]) vs chlorthalidone at 2 years were significantly lower than 1.0 (P <. 01). There was no significant association of FG level change at 2 years with subsequent coronary heart disease, stroke, cardiovascular disease, total mortality, or endstage renal disease. There was no significant association of incident DM at 2 years with clinical outcomes, except for coronary heart disease ( risk ratio, 1.64; P=. 006), but the risk ratio was lower and nonsignificant in the chlorthalidone group ( risk ratio, 1.46; P=. 14). Conclusions: Fasting glucose levels increase in older adults with hypertension regardless of treatment type. For those taking chlorthalidone vs other medications, the risk of developing FG levels higher than 125 mg/dL (6.9 mmol/L) is modestly greater, but there is no conclusive or consistent evidence that this diuretic-associated increase in DM risk increases the risk of clinical events. C1 Univ Texas, Sch Publ Hlth, Coordinating Ctr Clin Trials, Houston, TX 77030 USA. Emory Univ, Sch Med, Kaiser Permanente, Atlanta, GA 30322 USA. Emory Univ, Sch Med, Div Endocrinol, Atlanta, GA 30322 USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Tulane Univ, Hlth Sci Ctr, New Orleans, LA 70118 USA. Med Univ S Carolina, Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29425 USA. Hennepin Cty Med Ctr, Div Clin Epidemiol, Minneapolis, MN 55415 USA. Ong Med Ctr, Oxon Hill, MD USA. St Vincent Char Hosp & Hlth Ctr, Lipid Res Ctr, Cleveland, OH USA. Wake Forest Univ, Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27109 USA. RP Davis, BR (reprint author), Univ Texas, Sch Publ Hlth, Coordinating Ctr Clin Trials, 1200 Herman Pressler St,Suite E801, Houston, TX 77030 USA. EM barry.r.davis@uth.tmc.edu FU NHLBI NIH HHS [N01-HC-35130] NR 30 TC 147 Z9 153 U1 1 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD NOV 13 PY 2006 VL 166 IS 20 BP 2191 EP 2201 DI 10.1001/archinte.166.20.2191 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 104VF UT WOS:000241987500005 PM 17101936 ER PT J AU Cho, EY Chen, WY Hunter, DJ Stampfer, MJ Colditz, GA Hankinson, SE Willett, WC AF Cho, Eunyoung Chen, Wendy Y. Hunter, David J. Stampfer, Meir J. Colditz, Graham A. Hankinson, Susan E. Willett, Walter C. TI Red meat intake and risk of breast cancer among premenopausal women SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID HORMONE-RECEPTOR STATUS; ESTROGEN-RECEPTOR; POSTMENOPAUSAL WOMEN; FOOD-CONSUMPTION; YOUNG-WOMEN; DIETARY-FAT; PROGESTERONE; EXPOSURE; ALCOHOL; IRON AB Background: The association between red meat intake and breast cancer is unclear, but most studies have assessed diet in midlife or later. Although breast tumors differ clinically and biologically by hormone receptor status, few epidemiologic studies of diet have made this distinction. Methods: Red meat intake and breast cancer risk were assessed among premenopausal women aged 26 to 46 years in the Nurses' Health Study II. Red meat intake was assessed with a food frequency questionnaire administered in 1991, 1995, and 1999, with respondents followed up through 2003. Breast cancers were self-reported and confirmed by review of pathologic reports. Results: During 12 years of follow-up of 90 659 premenopausal women, we documented 1021 cases of invasive breast carcinoma. Greater red meat intake was strongly related to elevated risk of breast cancers that were estrogen and progesterone receptor positive (ER +/ PR +; n= 512) but not to those that were estrogen and progesterone receptor negative (ER-/PR-; n= 167). Compared with those eating 3 or fewer servings per week of red meat, the multivariate relative risks (95% confidence intervals) for ER +/ PR+ breast cancer with increasing servings of red meat intake were 1.14 (0.90-1.45) for more than 3 to 5 or fewer servings per week, 1.42 (1.06-1.90) for more than 5 per week to 1 or fewer servings per day, 1.20 (0.89-1.63) for more than 1 to 1.5 or fewer servings per day, and 1.97 (1.35-2.88) for more than 1.5 servings per day (test for trend, P=.001). The corresponding relative risks for ER-/PR- breast cancer were 1.34 (0.89-2.00), 1.21 (0.73-2.00), 0.69 (0.39-1.23), and 0.89 (0.43-1.84) (test for trend, P=. 28). Higher intakes of several individual red meat items were also strongly related to elevated risk of ER +/PR+ breast cancer. Conclusion: Higher red meat intake may be a risk factor for ER+/PR+ breast cancer among premenopausal women. C1 Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Ctr Canc Prevent, Boston, MA 02115 USA. RP Cho, EY (reprint author), Brigham & Womens Hosp, Channing Lab, Dept Med, 181 Longwood Ave, Boston, MA 02115 USA. EM Eunyoung.Cho@channing.harvard.edu RI Colditz, Graham/A-3963-2009 OI Colditz, Graham/0000-0002-7307-0291 FU NCI NIH HHS [CA50385]; NIDDK NIH HHS [P30 DK040561, P30 DK040561-11] NR 45 TC 104 Z9 107 U1 2 U2 13 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD NOV 13 PY 2006 VL 166 IS 20 BP 2253 EP 2259 DI 10.1001/archinte.166.20.2253 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 104VF UT WOS:000241987500013 PM 17101944 ER PT J AU Taha, TA El-Alwani, M Hannun, YA Obeid, LM AF Taha, Tarek A. El-Alwani, Mazen Hannun, Yusuf A. Obeid, Lina M. TI Sphingosine kinase-1 is cleaved by cathepsin B in vitro: Identification of the initial cleavage sites for the protease SO FEBS LETTERS LA English DT Article DE sphingosine kinase; cathepsin B; proteases ID LYSOSOMAL CYSTEINE PROTEASES; PLASMA-MEMBRANE; CYTOCHROME-C; CELL-DEATH; APOPTOSIS; RELEASE; EXPRESSION; SPHINGOSINE-1-PHOSPHATE; PROGRESSION; ACTIVATION AB Previous work has identified sphingosine kinase-1 (SKI) as a substrate for the cysteine protease cathepsin B in vitro. In this study, the mechanism of SKI cleavage by cathepsin B was investigated. We identified two initial cleavage sites for the protease, the first at histidine 122 and the second at arginine 199. Mutation analysis showed that replacement of histidine 122 with a tyrosine maintained the activity of SKI while significantly reducing cleavage by cathepsin B at the initial cleavage site. The efficacy of cleavage of SKI at arginine 199, however, was not affected. These studies demonstrate that SKI is cleaved by cathepsin B in a sequential manner after basic amino acids, and that the initial cleavages at the two identified sites occur independently of each other. (c) 2006 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. C1 Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Ralph H Johnson Vet Adm Hosp, Div Gen Internal Med, Charleston, SC 29401 USA. Med Univ S Carolina, Charleston, SC 29425 USA. RP Obeid, LM (reprint author), Med Univ S Carolina, Dept Med, 114 Doughty St,POB 250779, Charleston, SC 29425 USA. EM obeidl@musc.edu OI obeid, lina/0000-0002-0734-0847 FU NCI NIH HHS [P01 CA097132] NR 26 TC 17 Z9 17 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD NOV 13 PY 2006 VL 580 IS 26 BP 6047 EP 6054 DI 10.1016/j.febslet.2006.09.070 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 108II UT WOS:000242233100004 PM 17064696 ER PT J AU Hyams, KC AF Hyams, Kenneth Craig TI Mental health screening before troop deployment SO BRITISH MEDICAL JOURNAL LA English DT Editorial Material ID GULF-WAR; MORTALITY; VETERANS; MILITARY C1 US Dept Vet Affairs, Off Publ Hlth & Environm Hazards, Washington, DC 20420 USA. RP Hyams, KC (reprint author), US Dept Vet Affairs, Off Publ Hlth & Environm Hazards, Washington, DC 20420 USA. EM Kenneth.Hyams@va.gov NR 8 TC 7 Z9 8 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0959-8146 J9 BRIT MED J JI Br. Med. J. PD NOV 11 PY 2006 VL 333 IS 7576 BP 979 EP 980 DI 10.1136/bmj.39023.648970.80 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 108GX UT WOS:000242229400001 PM 17095759 ER PT J AU Cao, Q Mak, KM Lieber, CS AF Cao, Qi Mak, Ki M. Lieber, Charles S. TI DLPC and SAMe prevent alpha 1(I) collagen mRNA up-regulation in human hepatic stellate cells, whether caused by leptin or menadione SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE dilinoleoylphosphatidylcholine; S-adenosylmethionine; leptin; menadione; hepatic stellate cells; alpha 1(I) collagen mRNA; H2O2; reduced glutathione; ERK1/2; p38 ID HYDROGEN-PEROXIDE; OXIDATIVE STRESS; RAT HEPATOCYTES; INHIBITOR; GLUTATHIONE; METABOLISM; EXPRESSION; FIBROSIS; ROLES; MAPK AB We previously reported that the combination of dilinoleoylphosphatidylcholine (DLPC) and S-adenosylmethionine (SAMe), which have antioxidant properties and antifibrogenic actions, prevented leptin-stimulated tissue inhibitor of metalloproteinase (TIMP)-1 production in hepatic stellate cells (HSCs) by inhibiting H2O2-mediated signal transduction. We now show that DLPC and SAMe inhibit alpha 1(I) collagen mRNA expression induced by leptin or menadione in LX-2 human HSCs. We found that DLPC and SAMe prevent H2O2 generation and restore reduced glutathione (GSH) depletion whether caused by leptin or menadione. Blocking H2O2 signaling through ERK1/2 and p38 pathways resulted in a complete inhibition of leptin or menadione-induced alpha 1(I) collagen mRNA. The inhibition of collagen mRNA by DLPC and SAMe combined is at least two times more effective than that by DLPC or SAMe alone. In conjunction with the prevention of TIMP-1 production, the ability of DLPC and SAMe to inhibit alpha 1(I) collagen mRNA expression provides a mechanistic basis for these innocuous compounds in the prevention of hepatic fibrosis, because enhanced TIMP-1 and collagen productions are associated with hepatic fibrogenesis and their attenuation may diminish fibrosis. (c) 2006 Elsevier Inc. All rights reserved. C1 Mt Sinai Sch Med, James J Peters Vet Affairs Med Ctr, Ctr Alcohol Res & Treatment, Bronx, NY 10468 USA. RP Lieber, CS (reprint author), Mt Sinai Sch Med, James J Peters Vet Affairs Med Ctr, Ctr Alcohol Res & Treatment, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM LIEBERCS@AOL.COM FU NCCIH NIH HHS [R01 AT001583, AT001583] NR 21 TC 7 Z9 7 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 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD NOV 10 PY 2006 VL 350 IS 1 BP 50 EP 55 DI 10.1016/j.bbrc.2006.08.174 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 094AZ UT WOS:000241212700007 PM 16996477 ER PT J AU Fu, JR Lin, GS Zeng, B Wu, ZW Wu, YX Chu, HG Qin, GJ Liang, G Li, JN Gan, X Yu, XL Li, CH Liu, DX AF Fu, Jinrong Lin, Guosheng Zeng, Bin Wu, Zhiwei Wu, Yanxia Chu, Honggang Qin, Gangjian Liang, Gong Li, Jinan Gan, Xiang Yu, Xiaolan Li, Chunhua Liu, Dongxu TI Anti-ischemia/reperfusion of C1 inhibitor in myocardial cell injury via regulation of local myocardial C3 activity SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE complement; C1 inhibitor; C3; hemolysis; cardiomyocyte; ischemia; reperfusion ID CORONARY-ARTERY OCCLUSION; ISCHEMIA-REPERFUSION INJURY; ESTERASE INHIBITOR; COMPLEMENT-PATHWAY; INFLAMMATION; NECROSIS; THERAPY; ACTIVATION; EXPRESSION; INFARCTION AB C3 is common to all pathways of complement activation augmenting ischemia/reperfusion (I/R)-induced myocardial injury and cardiac dysfunction. Complement inhibition with the complement regulatory protein, C1 inhibitor (C1INH), obviously exerts cardioprotective effects. Here, we examine whether C1INH regulates C3 activity in the ischemic myocardial tissue. C1INH markedly suppressed C3 mRNA expression and protein synthesis in both a model of I/R-induced rat acute myocardial infarction (AMI) and the cultured rat H9c2 heart myocytes. At least, this regulation was at the transcriptional level in response to oxygen tension. In vitro, C3 deposition on, and binding to, the surface of rat myocardial cells were significantly blocked by C1INH treatment. C1INH could inhibit classical complement-mediated cell lysis via suppressing the biological activity of C3. Therefore, C1INH, in addition to inhibition of the systemic complement activation, prevents myocardial cell injury via a direct inhibitory role in the local myocardial C3 activity. (c) 2006 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Wuhan Univ, Renmin Hosp, Sch Med, Dept Cardiol, Wuhan 430072, Hubei, Peoples R China. Tufts Univ, Sch Med, Caritas St Elixabeths Med Ctr, Boston, MA 02111 USA. Harvard Univ, Childrens Hosp, Sch Med, Boston, MA 02115 USA. Hubei Univ, Sch Life Sci, Ctr Infect & Immun Res, Wuhan, Hubei, Peoples R China. RP Liu, DX (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, 800 Huntington Ave, Boston, MA 02115 USA. EM lgs1027_phb@163.com; dliu@cbrinstitute.org NR 33 TC 14 Z9 14 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD NOV 10 PY 2006 VL 350 IS 1 BP 162 EP 168 DI 10.1016/j.bbrc.2006.09.023 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 094AZ UT WOS:000241212700023 PM 16996480 ER PT J AU Spassieva, S Seo, JG Jiang, JC Bielawski, J Alvarez-Vasquez, F Jazwinski, SM Hannun, YA Obeid, LM AF Spassieva, Stefka Seo, Jae-Gu Jiang, James C. Bielawski, Jacek Alvarez-Vasquez, Fernando Jazwinski, S. Michal Hannun, Yusuf A. Obeid, Lina M. TI Necessary role for the Lag1p motif in (dihydro)ceramide synthase activity SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LONGEVITY-ASSURANCE GENE; CERAMIDE SYNTHASE; FAMILY-MEMBERS; YEAST; COA; HOMOLOG; PROTEIN; CLONING; GROWTH; TRANSLOCATION AB Lag1 (longevity assurance gene 1) homologues, a family of transmembrane proteins found in all eukaryotes, have been shown to be necessary for (dihydro) ceramide synthesis. All Lag1 homologues contain a highly conserved stretch of 52 amino acids known as the Lag1p motif. However, the functional significance of the conserved Lag1p motif for (dihydro) ceramide synthesis is currently unknown. In this work, we have investigated the function of the motif by introducing eight point mutations in the Lag1p motif of the mouse LASS1 (longevity assurance homologue 1 of yeast Lag1). The (dihydro) ceramide synthase activity of the mutants was tested using microsomes in HeLa cells and in vitro. Six of the mutations resulted in loss of activity in cells and in vitro. In addition, our results showed that C18:0 fatty acid CoA (but not cis-C18:1 fatty acid CoAs) are substrates for LASS1 and that LASS1 in HeLa cells is sensitive to fumonisin B-1, an in vitro inhibitor of ( dihydro)ceramide synthase. Moreover, we mutated the Lag1p motif of another Lag homologue, human LASS5. The amino acid substitutions in the human LASS5 were the same as in mouse LASS1, and had the same effect on the in vitro activity of LASS5, suggesting the Lag1p motif appears to be essential for the enzyme activity of all Lag1 homologues. C1 Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Biostat Bioinformat & Epidemiol, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Hosp, Div Gen Internal Med, Charleston, SC 29401 USA. Louisiana State Univ, Hlth Sci Ctr, Dept Biochem & Mol Biol, New Orleans, LA 70112 USA. RP Obeid, LM (reprint author), Med Univ S Carolina, Dept Med, 114 Doughty St,POB 250779, Charleston, SC 29425 USA. EM obeidl@musc.edu OI obeid, lina/0000-0002-0734-0847 FU NCI NIH HHS [P01 CA97132]; NIA NIH HHS [AG016583, AG006168] NR 30 TC 64 Z9 67 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 NOV 10 PY 2006 VL 281 IS 45 BP 33931 EP 33938 DI 10.1074/jbc.M608092200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 101UZ UT WOS:000241767600014 PM 16951403 ER PT J AU Hwang, WC Lin, YQ Santelli, E Sui, JH Jaroszewski, L Stec, B Farzan, M Marasco, WA Liddington, RC AF Hwang, William C. Lin, Yaqiong Santelli, Eugenio Sui, Jianhua Jaroszewski, Lukasz Stec, Boguslaw Farzan, Michael Marasco, Wayne A. Liddington, Robert C. TI Structural basis of neutralization by a human anti-severe acute respiratory syndrome spike protein antibody, 80R SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SARS-CORONAVIRUS; MOLECULAR REPLACEMENT; RECEPTOR; DETERMINANTS; ENTRY AB Severe acute respiratory syndrome (SARS) is a newly emerged infectious disease that caused pandemic spread in 2003. The etiological agent of SARS is a novel coronavirus (SARS-CoV). The coronaviral surface spike protein S is a type I transmembrane glycoprotein that mediates initial host binding via the cell surface receptor angiotensin-converting enzyme 2 (ACE2), as well as the subsequent membrane fusion events required for cell entry. Here we report the crystal structure of the S1 receptor binding domain (RBD) in complex with a neutralizing antibody, 80R, at 2.3 angstrom resolution, as well as the structure of the uncomplexed S1 RBD at 2.2 angstrom resolution. We show that the 80R-binding epitope on the S1 RBD overlaps very closely with the ACE2-binding site, providing a rationale for the strong binding and broad neutralizing ability of the antibody. We provide a structural basis for the differential effects of certain mutations in the spike protein on 80R versus ACE2 binding, including escape mutants, which should facilitate the design of immunotherapeutics to treat a future SARS outbreak. We further show that the RBD of S1 forms dimers via an extensive interface that is disrupted in receptor- and antibody-bound crystal structures, and we propose a role for the dimer in virus stability and infectivity. C1 Burnham Inst Med Res, Infect & Inflammatory Dis Ctr, La Jolla, CA 92037 USA. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, New England Reg Primate Res Ctr, Dept Microbiol & Mol Genet, Southborough, MA 01772 USA. RP Liddington, RC (reprint author), Burnham Inst Med Res, Infect & Inflammatory Dis Ctr, 10901 N Torrey Pines Rd, La Jolla, CA 92037 USA. EM rlidding@burnham.org OI SUI, JIANHUA/0000-0002-1272-9662 FU NIAID NIH HHS [AI053822, AI061318, AI28785, AI48436] NR 28 TC 53 Z9 56 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 NOV 10 PY 2006 VL 281 IS 45 BP 34610 EP 34616 DI 10.1074/jbc.M603275200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 101UZ UT WOS:000241767600080 PM 16954221 ER PT J AU Earle, CC AF Earle, Craig C. TI Failing,to plan is planning to fail: Improving the quality of care with survivorship care plans SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID ROUTINE FOLLOW-UP; BREAST-CANCER; COLORECTAL-CANCER; CLINICAL-ONCOLOGY; AMERICAN-SOCIETY; RANDOMIZED-TRIAL; UPDATE; SURVEILLANCE; GUIDELINES; LIFE AB The recent Institute of Medicine report "From Cancer Patient to Cancer Survivor: Lost in Transition" recommended the creation of survivorship care plans for patients as they complete primary therapy for cancer to ensure clarity for all involved about patients' diagnoses, treatments received, and surveillance plans. Any previously existing follow-up guidelines for cancer survivors have been largely restricted to surveillance for recurrence of the primary disease, An important message of the Institute of Medicine report is that survivorship care plans must surpass this and address the chronic effects of cancer (pain, fatigue, premature menopause, depression/anxiety), monitoring for and preventing late effects like osteoporosis, heart disease, and second malignancies, and promoting healthy lifestyles. It should explicitly identify the providers responsible for each aspect of ongoing care and provide information on resources available for psychosocial and other practical issues that may arise as a result of the prior cancer diagnosis. Although having some sort of a plan is clearly necessary to achieve high quality care, there are practical barriers to formal off-treatment consultations and the creation of written documents that may become part of the medical record. This article reviews the elements of the proposed survivorship care plan and discusses areas of research and development needed to make them part of standard oncology practice. C1 Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Dept Med Oncol, Div Populat Sci, Boston, MA 02115 USA. RP Earle, CC (reprint author), Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Dept Med Oncol, Div Populat Sci, 44 Binney St,454-STE 21-24, Boston, MA 02115 USA. EM craig_earle@dfci.harvard.edu NR 23 TC 138 Z9 140 U1 0 U2 8 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV 10 PY 2006 VL 24 IS 32 BP 5112 EP 5116 DI 10.1200/JCO.2006.06.5284 PG 5 WC Oncology SC Oncology GA 109AM UT WOS:000242280300003 PM 17093272 ER PT J AU Benson, TE Brown, MC AF Benson, Thane E. Brown, M. Christian TI Ultrastructure of synaptic input to medial olivocochlear neurons SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE superior olivary complex; efferent; outer hair cell; cochlear nucleus; synaptic vesicle ID POSTEROVENTRAL COCHLEAR NUCLEUS; SUPERIOR OLIVARY COMPLEX; AUDITORY-NERVE RESPONSE; BUSHY CELL AXONS; GUINEA-PIG; INFERIOR COLLICULUS; EFFERENT NEURONS; ELECTRICAL-STIMULATION; BRAIN-STEM; HISTOCHEMICAL-LOCALIZATION AB Medial olivocochlear (MOC) neurons project from the brain to the cochlea to form the efferent limb of the MOC reflex. To study synaptic inputs to MOC neurons, we retrogradely labeled these neurons using horseradish peroxidase injections into the cochlea. Labeled neurons were identified in the ventral nucleus of the trapezoid body and documented with the light microscope before being studied with serial-section electron microscopy. MOC somata and dendrites were innervated by three different types of synapses, distinguished as either having: 1) large, round synaptic vesicles and forming asymmetric contacts; 2) small, round vesicles plus a few dense core vesicles and forming asymmetric contacts; or 3) pleomorphic vesicles and forming symmetric contacts. The first two types were the most frequent on somata. Acetylcholinesterase-stained material confirmed that the type containing large, round vesicles is most common on dendrites. We kept track of the synaptic terminals in serial sections and compiled them into three-dimensional swellings. Swellings with large, round vesicles formed up to seven synapses per swelling, were largest in size, and sometimes formed complex arrangements engulfing spines of MOC neurons. Swellings with small, round vesicles formed up to four synapses per swelling. The morphology of this type of synapse, and the moderate sizes of the swellings forming it, suggests that it originates from posteroventral cochlear nucleus stellate/multipolar neurons. This input may thus provide the sound-evoked input to MOC neurons that causes their reflexive response to sound. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Brown, MC (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, 243 Charles St, Boston, MA 02114 USA. EM mcb@epl.meei.harvard.edu FU NIDCD NIH HHS [DC 01089] NR 61 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 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD NOV 10 PY 2006 VL 499 IS 2 BP 244 EP 257 DI 10.1002/cne.21118 PG 14 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 088KA UT WOS:000240809400005 PM 16977616 ER PT J AU Rubin, RT Rhodes, ME Miller, TH Jakab, RL Czambel, RK AF Rubin, Robert T. Rhodes, Michael E. Miller, Thomas H. Jakab, Robert L. Czambel, R. Kenneth TI Sequence of pituitary-adrenal cortical hormone responses to low-dose physostigmine administration in young adult women and men SO LIFE SCIENCES LA English DT Article DE cholinergic; physostigmine; ACTH; cortisol; sex difference ID PRIMARY ENDOGENOUS-DEPRESSION; FUNCTIONAL SEX-DIFFERENCES; VASOPRESSIN MESSENGER-RNA; CHOLINERGIC STIMULATION; HUMAN HYPOTHALAMUS; EXTRAHYPOTHALAMIC VASOPRESSIN; NEUROTRANSMITTER REGULATION; DEXAMETHASONE SUPPRESSION; PARAVENTRICULAR NUCLEUS; NEUROENDOCRINE ASPECTS AB We previously demonstrated greater HPA axis activation in adult men compared to adult women following low-dose administration of the anticholinesterase inhibitor, physostigmine (PHYSO). Because blood sampling was done infrequently following PHYSO, the rise times of AVP, ACTH(1-39), and cortisol could not be determined. In the present study, we determined the sequence of hormone increases by frequent blood sampling following PHYSO. Twelve adult women and 12 adult men underwent three test sessions 5-7 days apart: PHYSO, saline control, and repeat PHYSO. As in the earlier study, PHYSO produced no side effects in half the subjects and mild side effects in the other half, with no significant female-male differences. None of the hormone responses was significantly correlated with the presence or absence of side effects. In both women and men, the AVP increase preceded the ACTH(1-39) increase, which in turn preceded the cortisol increase. The AVP and ACTH AUCs were significantly positively correlated in both women and men, supporting AVP as an acute stimulus to ACTH secretion. Also as in the earlier study, the AVP response to PHYSO was more than twice as great in men as in women, but the difference was not statistically significant. We therefore analyzed the results of both studies combined (N=26 women and 26 men). The men had a significantly greater AVP response and a trend toward a greater ACTH (1-39) response compared to the women. These findings further support the concept of sexual diergism (functional sex difference) in the influence of CNS cholinergic systems on HPA hormone secretion. (c) 2006 Elsevier Inc. All rights reserved. C1 VA Greater LA Healthcare Syst, Dept Psychiat & Mental Hlth 116A, Los Angeles, CA 90073 USA. St Vincent Coll, Dept Biol, Latrobe, PA 15650 USA. Univ Pittsburgh, Sch Nursing, Pittsburgh, PA 15260 USA. Drexel Univ, Coll Med, Neurosci Res Ctr, Pittsburgh, PA 15212 USA. Drexel Univ, Coll Med, Allegheny Gen Hosp, Neurosci Res Ctr, Pittsburgh, PA 15212 USA. RP Rubin, RT (reprint author), VA Greater LA Healthcare Syst, Dept Psychiat & Mental Hlth 116A, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM robert.rubin@va.gov FU NIMH NIH HHS [MH 028380] NR 58 TC 7 Z9 7 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0024-3205 J9 LIFE SCI JI Life Sci. PD NOV 10 PY 2006 VL 79 IS 24 BP 2260 EP 2268 DI 10.1016/j.lfs.2006.07.023 PG 9 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 108HG UT WOS:000242230300003 PM 16935309 ER PT J AU Carroll, M AF Carroll, Michael TI Immunology - Exposure of an executioner SO NATURE LA English DT Editorial Material ID COMPLEMENT FACTOR-H; COMPONENT; IMMUNITY C1 Harvard Univ, Sch Med, CBR, Inst Biomed Res, Boston, MA 02115 USA. RP Carroll, M (reprint author), Harvard Univ, Sch Med, CBR, Inst Biomed Res, 800 Huntington Ave, Boston, MA 02115 USA. EM carroll@cbr.med.harvard.edu NR 11 TC 3 Z9 3 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD NOV 9 PY 2006 VL 444 IS 7116 BP 159 EP 160 DI 10.1038/nature05307 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 103DZ UT WOS:000241867200027 PM 17051146 ER PT J AU Darouiche, RO AF Darouiche, Rabih O. TI Current concepts: Spinal epidural abscess SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID PROGNOSTIC FACTORS; CLINICAL PRESENTATION; MEDICAL-MANAGEMENT; INFECTIONS; ASPIRATION; INJECTION; ANALGESIA; PATHOLOGY C1 Baylor Coll Med, Ctr Protheses Infect, Houston, TX 77030 USA. Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Infect Dis Sect, Houston, TX 77030 USA. RP Darouiche, RO (reprint author), Baylor Coll Med, Ctr Protheses Infect, 1333 Moursund Ave,Suite A221, Houston, TX 77030 USA. EM rdarouiche@aol.com NR 45 TC 182 Z9 187 U1 2 U2 8 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 NOV 9 PY 2006 VL 355 IS 19 BP 2012 EP 2020 DI 10.1056/NEJMra055111 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 102SG UT WOS:000241833000009 PM 17093252 ER PT J AU Frankel, DS Johnson, PA Shepard, JAO Harris, NL Semigran, GE Jaffer, FA Neilan, TG Walker, JD Stone, JR Weinberg, AN AF Frankel, David S. Johnson, Paula A. Shepard, Jo-Anne O. Harris, Nancy Lee Semigran, Gail E. Jaffer, Farouc A. Neilan, Tomas G. Walker, Jennifer D. Stone, James R. Weinberg, Arnold N. TI Case 34-2006: A 72-year-old woman with nausea followed by hypotension and respiratory failure - Acute myocardial infarction (3 to 5 days old) with rupture of the anterolateral papillary muscle SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID CORONARY-HEART-DISEASE; GENDER-DIFFERENCES C1 Brigham & Womens Hosp, Div Womens Hlth, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Frankel, DS (reprint author), Brigham & Womens Hosp, Div Womens Hlth, 75 Francis St, Boston, MA 02115 USA. NR 12 TC 1 Z9 1 U1 0 U2 2 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 NOV 9 PY 2006 VL 355 IS 19 BP 2022 EP 2031 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 102SG UT WOS:000241833000013 PM 17093254 ER PT J AU Horhota, AT Szostak, JW McLaughlin, LW AF Horhota, Allen T. Szostak, Jack W. McLaughlin, Larry W. TI Glycerol nucleoside triphosphates: Synthesis and polymerase substrate activities SO ORGANIC LETTERS LA English DT Article ID NUCLEIC-ACID STRUCTURE; CHEMICAL ETIOLOGY; ALIPHATIC ANALOGS; EVOLUTION; RNA; NUCLEOTIDES; SYSTEM; TNA AB [GRAPHICS] The synthesis of (S)-glycerol nucleoside triphosphates (gNTPs) and the analysis of their substrate activities for enzymatic polymerization is described. NTPs with simplified carbohydrate backbones such as the tNTPs (alpha-L-threose-NTPs) are polymerase substrates and offer the potential to create non-natural aptamer sequences with simplified backbones through enzymatic means. The acyclic (S)-GNA was modeled after the shortened alpha-threofuranosyl backbone. Here we describe the synthesis of (S)-glycerol NTPs and initial enzymatic testing of this further simplified nucleic acid backbone. C1 Boston Coll, Merkert Chem Ctr, Dept Chem, Chestnut Hill, MA 02467 USA. Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Horhota, AT (reprint author), Boston Coll, Merkert Chem Ctr, Dept Chem, Chestnut Hill, MA 02467 USA. EM mclaughl@bc.edu NR 17 TC 26 Z9 26 U1 2 U2 24 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1523-7060 J9 ORG LETT JI Org. Lett. PD NOV 9 PY 2006 VL 8 IS 23 BP 5345 EP 5347 DI 10.1021/ol062232u PG 3 WC Chemistry, Organic SC Chemistry GA 101GQ UT WOS:000241729500043 PM 17078714 ER PT J AU Boockvar, KS Meier, DE AF Boockvar, Kenneth S. Meier, Diane E. TI Palliative care for frail older adults - "There are things I can't do anymore that I wish I could ..." SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID OF-LIFE CARE; CONTROLLED-TRIAL; ELDERLY PEOPLE; INSTRUMENTAL ACTIVITIES; GERIATRIC DEPRESSION; FUNCTIONAL DECLINE; PHYSICAL FRAILTY; PAIN MANAGEMENT; WOMENS HEALTH; DOUBLE-BLIND AB Frailty in older adults is increasingly a recognized syndrome of decline, sometimes subtle, in function and health that may be amenable to available approaches to care. Frailty manifests the following core clinical features: loss of strength, weight loss, low levels of activity, poor endurance or fatigue, and slowed performance. The presence of 3 or more of these features is associated with adverse outcomes including falls, new or worsened function impairment, hospitalization, and death. In this article, we use the case of Mrs K to describe the challenges of recognizing frailty in clinical practice, common problems and symptoms that frail older adults experience, and approaches to these issues that clinicians may incorporate into their practices. We discuss the importance of advance care planning, provider-patient communication, and appropriate palliative care and hospice referral for frail older adults. Frailty is associated with symptomatic long-term disease, decline in function, and abbreviated survival. Therefore, when frailty is severe, delivery of palliative care focused on relief of discomfort and enhancement of quality of life is highly appropriate. The application of multidisciplinary, team-based palliative approaches and of up-to-date geriatrics knowledge is beneficial for treating these patients because of the complexity of their coexisting social, psychological, and medical needs. C1 James J Peters Vet Affairs Med Ctr, Bronx, NY 10468 USA. CUNY Mt Sinai Sch Med, New York, NY 10029 USA. Jewish Home & Hosp, New York, NY USA. RP Boockvar, KS (reprint author), James J Peters Vet Affairs Med Ctr, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM kenneth.boockvar@mssm.edu OI Boockvar, Kenneth/0000-0003-1165-5558 NR 77 TC 40 Z9 41 U1 2 U2 9 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 8 PY 2006 VL 296 IS 18 BP 2245 EP 2253 DI 10.1001/jama.296.18.2245 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 102QM UT WOS:000241827700025 PM 17090771 ER PT J AU Li, GD Chiara, DC Sawyer, GW Husain, SS Olsen, RW Cohen, JB AF Li, Guo-Dong Chiara, David C. Sawyer, Gregory W. Husain, S. Shaukat Olsen, Richard W. Cohen, Jonathan B. TI Identification of a GABA(A) receptor anesthetic binding site at subunit interfaces by photolabeling with an etomidate analog SO JOURNAL OF NEUROSCIENCE LA English DT Article DE GABA(A) receptor; anesthesia; structure; photolabeling; nicotinic receptor; muscimol; binding; etomidate ID GAMMA-AMINOBUTYRIC-ACID; NICOTINIC ACETYLCHOLINE-RECEPTOR; BOVINE CEREBRAL-CORTEX; GATED ION CHANNELS; A RECEPTOR; ALPHA-SUBUNIT; AMINO-ACID; COMPLEX; PROTEIN; PURIFICATION AB General anesthetics, including etomidate, act by binding to and enhancing the function of GABA type A receptors (GABA(A)Rs), which mediate inhibitory neurotransmission in the brain. Here, we used a radiolabeled, photoreactive etomidate analog ([H-3] azietomidate), which retains anesthetic potency in vivo and enhances GABA(A)R function in vitro, to identify directly, for the first time, amino acids that contribute to a GABA(A)R anesthetic binding site. For GABA(A)Rs purified by affinity chromatography from detergent extracts of bovine cortex, [H-3] azietomidate photoincorporation was increased by GABA and inhibited by etomidate in a concentration-dependent manner (IC50 = 30 mu M). Protein microsequencing of fragments isolated from proteolytic digests established photolabeling of two residues: one within the alpha M1 transmembrane helix at alpha 1Met-236 (and/or the homologous methionines in alpha 2,3,5), not previously implicated in etomidate function, and one within the beta M3 transmembrane helix at beta 3Met-286 ( and/or the homologous methionines in beta 1,2), an etomidate sensitivity determinant. The pharmacological specificity of labeling indicates that these methionines contribute to a single binding pocket for etomidate located in the transmembrane domain at the interface between beta and alpha subunits, in what is predicted by structural models based on homology with the nicotinic acetylcholine receptor to be a water-filled pocket similar to 50 angstrom below the GABA binding site. The localization of the etomidate binding site to an intersubunit, not an intrasubunit, binding pocket is a novel conclusion that suggests more generally that the localization of drug binding sites to subunit interfaces may be a feature not only for GABA and benzodiazepines but also for etomidate and other intravenous and volatile anesthetics. C1 Univ Calif Los Angeles, Dept Mol & Med Pharmacol, Geffen Sch Med, Los Angeles, CA 90095 USA. Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Cohen, JB (reprint author), Univ Calif Los Angeles, Dept Mol & Med Pharmacol, Geffen Sch Med, Los Angeles, CA 90095 USA. EM jonathan_cohen@hms.harvard.edu OI Sawyer, Gregory/0000-0003-4612-3754 FU NIGMS NIH HHS [GM58448] NR 46 TC 182 Z9 184 U1 0 U2 7 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 NOV 8 PY 2006 VL 26 IS 45 BP 11599 EP 11605 DI 10.1523/JNEUROSCI.3467-06.2006 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 103NE UT WOS:000241892700011 PM 17093081 ER PT J AU Li, JD Hu, WP Boehmer, L Cheng, MY Lee, AG Jilek, A Siegel, JM Zhou, QY AF Li, Jia-Da Hu, Wang-Ping Boehmer, Lisa Cheng, Michelle Y. Lee, Alex G. Jilek, Alexander Siegel, Jerome M. Zhou, Qun-Yong TI Attenuated circadian rhythms in mice lacking the prokineticin 2 gene SO JOURNAL OF NEUROSCIENCE LA English DT Article DE circadian rhythm; prokineticin 2; knock-out; suprachiasmatic nucleus; sleep; locomotor ID SUPRACHIASMATIC NUCLEUS; LOCOMOTOR-ACTIVITY; EFFERENT PROJECTIONS; OLFACTORY BULBECTOMY; PERIPHERAL-TISSUES; BODY-TEMPERATURE; CLOCK; SLEEP; RAT; VASOPRESSIN AB Circadian clocks drive daily rhythms in virtually all organisms. In mammals, the suprachiasmatic nucleus (SCN) is recognized as the master clock that synchronizes central and peripheral oscillators to evoke circadian rhythms of diverse physiology and behavior. How the timing information is transmitted from the SCN clock to generate overt circadian rhythms is essentially unknown. Prokineticin 2 (PK2), a clock-controlled gene that encodes a secreted protein, has been indicated as a candidate SCN clock output signal that regulates circadian locomotor rhythm. Here we report the generation and analysis of PK2-null mice. The reduction of locomotor rhythms in PK2-null mice was apparent in both hybrid and inbred genetic backgrounds. PK2-null mice also displayed significantly reduced rhythmicity for a variety of other physiological and behavioral parameters, including sleep-wake cycle, body temperature, circulating glucocorticoid and glucose levels, as well as the expression of peripheral clock genes. In addition, PK2-null mice showed accelerated acquisition of food anticipatory activity during a daytime food restriction. We conclude that PK2, acting as a SCN output factor, is important for the maintenance of robust circadian rhythms. C1 Univ Calif Irvine, Dept Pharmacol, Irvine, CA 92697 USA. Univ Calif Los Angeles, Sch Med, Dept Psychiat, Vet Adm Greater Los Angeles Healthcare Syst Sepul, North Hills, CA 91343 USA. Univ Calif Los Angeles, Sch Med, Brain Res Inst, North Hills, CA 91343 USA. Johannes Kepler Univ Linz, Inst Organ Chem, A-4040 Linz, Austria. RP Zhou, QY (reprint author), Univ Calif Irvine, Dept Pharmacol, Irvine, CA 92697 USA. EM qzhou@uci.edu FU NIMH NIH HHS [R01 MH067753-05, MH067753] NR 55 TC 88 Z9 90 U1 2 U2 7 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 NOV 8 PY 2006 VL 26 IS 45 BP 11615 EP 11623 DI 10.1523/JNEUROSCI.3679-06.2006 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 103NE UT WOS:000241892700013 PM 17093083 ER PT J AU Desai, J Yassa, L Marqusee, E George, S Frates, MC Chen, MH Morgan, JA Dychter, SS Larsen, PR Demetri, GD Alexander, EK AF Desai, Jayesh Yassa, Leila Marqusee, Ellen George, Suzanne Frates, Mary C. Chen, Ming Hui Morgan, Jeffrey A. Dychter, Samuel S. Larsen, P. Reed Demetri, George D. Alexander, Erik K. TI Hypothyroidism after sunitinib treatment for patients with gastrointestinal stromal tumors SO ANNALS OF INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 77th Annual Meeting of the American-Thyroid-Association CY OCT 11-15, 2006 CL Phoenix, AZ SP Amer Thyroid Assoc ID THYROID-DYSFUNCTION; IMATINIB MESYLATE; THERAPY; CANCER; CARCINOMA; INHIBITOR; SU11248 AB Background: Sunitinib malate is an oral tyrosine kinase inhibitor recently approved for the treatment of gastrointestinal stromal tumors and renal cell carcinoma. Because the ret proto-oncogene is also inhibited by this agent, clinical evaluation of thyroid function was performed. Objective: To describe the prevalence and clinical presentation of thyroid dysfunction related to sunitinib therapy. Design: Prospective, observational cohort study. Setting: Tertiary care hospital. Patients: 42 patients treated for a median of 37 weeks (range, 10 to 167 weeks). Measurements: Following analysis of serial thyroid-stimulating hormone (TSH) measurements collected prospectively during a clinical trial of sunitinib, the authors determined the proportion of patients with thyroid dysfunction. Results: Abnormal serum TSH concentrations were documented in 26 of 42 patients (62%): 15 (36%) developed persistent, primary hypothyroidism; 4 (10%) developed isolated TSH suppression; and 7 (17%) experienced transient, mild TSH elevations. The risk for hypothyroidism increased with the duration of sunitinib therapy. Six of 15 (40%) hypothyroid patients had suppressed TSH concentrations before developing hypothyroidism, suggesting thyroiditis. Two hypothyroid patients evaluated with thyroid ultrasonography had no visualized thyroid tissue despite normal baseline thyroid function. Limitations: The exploratory nature of this study precluded more frequent biochemical and sonographic analysis that may better define the mechanism of sunitinib-associated thyroid dysfunction. Conclusion: Hypothyroidism is a frequent complication of sunitinib therapy. Regular surveillance of thyroid function is warranted in patients receiving the drug. Although the mechanism by which this complication occurs is unknown, the observations of preceding TSH suppression and subsequent absence of visualized thyroid tissue in some patients suggest that sunitinib may induce a destructive thyroiditis through follicular cell apoptosis. This provides a rationale for further investigation of sunitinib treatment in patients with advanced thyroid cancer. C1 Brigham & Womens Hosp, Div Endocrinol Diabet & Metab, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Pfizer Inc, New York, NY USA. RP Alexander, EK (reprint author), Brigham & Womens Hosp, Div Endocrinol Diabet & Metab, Dana Farber Canc Inst, 75 Francis St,PPB B4, Boston, MA 02115 USA. EM ekalexander@partners.org FU NIDDK NIH HHS [T32 DK007529] NR 17 TC 232 Z9 241 U1 2 U2 8 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 NOV 7 PY 2006 VL 145 IS 9 BP 660 EP 664 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 100ZD UT WOS:000241707800004 PM 17088579 ER PT J AU Casarett, D AF Casarett, David TI The median is not the (only) message SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material ID BREAST-CARCINOMA TREATMENT; LUNG-CANCER; OLDER WOMEN; PATIENT C1 Univ Penn, Ctr Hlth Equ Res & Promot, Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. RP Casarett, D (reprint author), Univ Penn, Ctr Hlth Equ Res & Promot, Philadelphia Vet Affairs Med Ctr, 3615 Chestnut St, Philadelphia, PA 19104 USA. EM casarett@mail.med.upenn.edu NR 15 TC 5 Z9 5 U1 0 U2 0 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 NOV 7 PY 2006 VL 145 IS 9 BP 700 EP 701 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 100ZD UT WOS:000241707800010 PM 17088585 ER PT J AU Pinto, DS Kirtane, AJ Nallamothu, BK Murphy, SA Cohen, DJ Laham, RJ Cutlip, DE Bates, ER Frederick, PD Miller, DP Carrozza, JP Antman, EM Cannon, CP Gibson, CM AF Pinto, Duane S. Kirtane, Ajay J. Nallamothu, Brahmajee K. Murphy, Sabina A. Cohen, David J. Laham, Roger J. Cutlip, Donald E. Bates, Eric R. Frederick, Paul D. Miller, Dave P. Carrozza, Joseph P., Jr. Antman, Elliott M. Cannon, Christopher P. Gibson, C. Michael TI Hospital delays in reperfusion for ST-elevation myocardial infarction - Implications when selecting a reperfusion strategy SO CIRCULATION LA English DT Article DE myocardial infarction; angioplasty; fibrinolysis; survival; plasminogen activators ID PERCUTANEOUS CORONARY INTERVENTION; TO-BALLOON TIME; PRIMARY ANGIOPLASTY; NATIONAL-REGISTRY; FIBRINOLYTIC THERAPY; UNITED-STATES; VENTRICULAR-FUNCTION; POOLED ANALYSIS; MORTALITY; IMPACT AB Background - It has been suggested that the survival benefit associated with primary percutaneous coronary intervention (PPCI) in ST-segment elevation myocardial infarction may be attenuated if door-to-balloon (DB) time is delayed by > 1 hour beyond door-to-needle (DN) times for fibrinolytic therapy. Whereas DB times are rapid in randomized trials, they are often prolonged in routine practice. We hypothesized that in clinical practice, longer DB-DN times would be associated with higher mortality rates and reduced PPCI survival advantage. We also hypothesized that in addition to PPCI delays, patient risk factors would significantly modulate the relative survival advantage of PPCI over fibrinolysis. Methods and Results - DB-DN times were calculated by subtracting median DN time from median DB time at a hospital using data from 192 509 patients at 645 National Registry of Myocardial Infarction hospitals. Hierarchical models that adjusted simultaneously for both patient-level risk factors and hospital-level covariates were used to evaluate the relationship between PCI-related delay, patient risk factors, and in-hospital mortality. Longer DB-DN times were associated with increased mortality (P < 0.0001). The DB-DN time at which mortality rates with PPCI were no better than that of fibrinolysis varied considerably depending on patient age, symptom duration, and infarct location. Conclusions - As DB-DN times increase, the mortality advantage of PPCI over fibrinolysis declines, and this advantage varies considerably depending on patient characteristics. As indicated in the American College of Cardiology/American Heart Association guidelines, both the hospital-based PPCI-related delay (DB-DN time) and patient characteristics should be considered when a reperfusion strategy is selected. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Intervent Sect,Div Cardiol,TIMI Study Grp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Cardiovasc Div,Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. Univ Michigan, Div Cardiovasc, Ann Arbor, MI 48109 USA. Ovat Res Grp, San Francisco, CA USA. RP Gibson, CM (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Intervent Sect,Div Cardiol,TIMI Study Grp, 185 Pilgrim Rd, Boston, MA 02115 USA. EM mgibson@perfuse.org OI Frederick, Paul/0000-0002-7936-5488 NR 23 TC 262 Z9 280 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 7 PY 2006 VL 114 IS 19 BP 2019 EP 2025 DI 10.1161/CIRCULATIONAHA.106.638353 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 124XP UT WOS:000243406100007 PM 17075010 ER PT J AU Culley, DJ Yukhananov, RY Xie, ZC Gali, RR Tanzi, RE Crosby, G AF Culley, Deborah J. Yukhananov, Rustam Y. Xie, Zhongcong Gali, Reddy R. Tanzi, Rudolph E. Crosby, Gregory TI Altered hippocampal gene expression 2 days after general anesthesia in rats SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE gene expression; isoflurane; nitrous oxide; anesthesia; hippocampus; (rat) ID ACTIVATED PROTEIN-KINASES; NITROUS-OXIDE; SLICE CULTURES; ISOFLURANE; BRAIN; NEUROPROTECTION; EXPOSURE; TRANSMISSION; IMPAIRMENT; MECHANISMS AB We profiled changes in gene expression in the hippocampus 2 days after a 4 h general anesthetic with isoflurane and nitrous oxide. Eighteen month old Fisher 344 rats were anesthetized for 4 h with 1.2% isoflurane and 70% nitrous oxide (N=9) whereas control rats breathed 30% oxygen for 4 h (N=9). Rats were sacrificed 48 h later and RNA extracted from the hippocampus for gene expression profiling. Three gene arrays were used per group, with samples prepared by pooling RNA from three rats. Differentially expressed genes were analyzed based on a weighted error statistical model. Microarray results for 6 differentially expressed genes were verified with reverse transcriptase polymerase chain reaction. Compared to unanesthetized controls, 297 genes were diffierentially expressed 2 days following anesthesia (P < 0.05). Of these, 113 are named genes; 64% were up-regulated and 36% were down-regulated. The majority of differentially expressed genes are implicated in cell stress and replication, signal transduction, transcription, protein biosynthesis, cell structure, and metabolism. The correlation between fold changes on array and reverse transcriptase polymerase chain reaction was good (R-2=0.85) for the 6 genes examined with both methods. These results demonstrate that in rats general anesthesia is associated with persistent changes in hippocampal gene expression, suggesting that recovery of the brain from anesthesia is considerably slower than generally recognized. (c) 2006 Elsevier B.V. All rights reserved. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Anesthesia, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia, Boston, MA 02114 USA. Harvard Univ, Bauer Ctr Genom Res, Cambridge, MA 02138 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Genet & Aging Res Unit, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Div Aging, Boston, MA 02115 USA. RP Crosby, G (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Anesthesia, Boston, MA 02115 USA. EM gcrosby@zeus.bwh.harvard.edu FU NIA NIH HHS [AG 014713, K12 AG 000294, P60 AG008812, R01 AG20253]; NIGMS NIH HHS [K08 GM077057]; NIMH NIH HHS [MH 60009]; NINDS NIH HHS [K08 NS048140] NR 34 TC 31 Z9 32 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD NOV 7 PY 2006 VL 549 IS 1-3 BP 71 EP 78 DI 10.1016/j.ejphar.2006.08.028 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 094FS UT WOS:000241225700010 PM 16979155 ER PT J AU Obel, OA d'Avila, A Neuzil, P Saad, EB Ruskin, JN Reddy, VY AF Obel, Owen A. d'Avila, Andre Neuzil, Petr Saad, Eduardo B. Ruskin, Jeremy N. Reddy, Vivek Y. TI Ablation of left ventricular epicardial outflow tract tachycardia from the distal great cardiac vein SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID RADIOFREQUENCY CATHETER ABLATION; CORONARY-SINUS; AORTIC SINUS; ARTERY AB OBJECTIVES The purpose of this study was to examine the feasibility and safety of ablation of idiopathic outflow tract ventricular tachycardia (OTVT) from the distal ramifications of the coronary sinus (CS). BACKGROUND A significant minority of patients presenting with idiopathic OTVT have an epicardial focus, the standard approach to which involves ablation from within one of the aortic valve cusps (AVCs). We describe the successful ablation of idiopathic epicardial OTVT from within the CS in the distal great cardiac vein (GCV). METHODS Ablation from the distal GCV was performed in 5 patients with idiopathic OTVT who had unfavorable mapping, in some cases unsuccessful ablation from various endocardial and epicardial sites including the AVCs, and in 1 patient via the direct epicardial approach. An electroanatomic mapping system (Carto) was used in 3 patients, and conventional mapping was performed in 2 patients, and in 3 patients cryothermal ablation was performed. RESULTS In all patients, the first ablation lesion in the GCV successfully eliminated the arrhythmia. All patients have remained free of VT after a mean follow-up of 24 (7 to 44) months. There were no immediate or long-term complications. CONCLUSIONS Idiopathic epicardial OTVT can be successfully ablated from the distal GCV, and should be seen as an alternative to ablation from the aortic valve cusps. C1 Harvard Univ, Massachusetts Gen Hosp, Card Arrhythmia Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02138 USA. Pro Cardiaco Hosp, Cardiac Arrhythmia Serv, Rio De Janeiro, Brazil. Na Homolce Hosp, Div Cardiol, Electrophysiol Sect, Prague, Czech Republic. RP Reddy, VY (reprint author), Harvard Univ, Massachusetts Gen Hosp, Card Arrhythmia Serv, 55 Fruit St,Gray Bigelow 109, Boston, MA 02114 USA. EM vreddy@partners.org RI d'Avila, Andre/A-7693-2009; d'Avila, Andre Luiz/F-8009-2010 OI d'Avila, Andre Luiz/0000-0001-8769-1411 FU NHLBI NIH HHS [K23 HL68064-02] NR 18 TC 53 Z9 56 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD NOV 7 PY 2006 VL 48 IS 9 BP 1813 EP 1817 DI 10.1016/j.jacc.2006.06.006 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 102IO UT WOS:000241804400014 PM 17084255 ER PT J AU Tawakol, A Migrino, RQ Bashian, GG Bedri, S Vermylen, D Cury, RC Yates, D LaMuraglia, GM Furie, K Houser, S Gewirtz, H Muller, JE Brady, TJ Fischman, AJ AF Tawakol, Ahmed Migrino, Raymond Q. Bashian, Gregory G. Bedri, Shahinaz Vermylen, David Cury, Ricardo C. Yates, Denise LaMuraglia, Glenn M. Furie, Karen Houser, Stuart Gewirtz, Henry Muller, James E. Brady, Thomas J. Fischman, Alan J. TI In vivo F-18-fluorodeoxyglucose positron emission tomography imaging provides a noninvasive measure of carotid plaque inflammation in patients SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID C-REACTIVE PROTEIN; ARTERY STENOSIS; RISK-FACTORS; BLOOD-FLOW; RUPTURE; ENDARTERECTOMY; LESIONS; DEATH; CELLS; ATHEROSCLEROSIS AB OBJECTIVES Given the importance of inflammation in atherosclerosis, we sought to determine if atherosclerotic plaque inflammation could be measured noninvasively in humans using positron emission tomography (PET). BACKGROUND Earlier PET studies using fluorodeoxyglucose (FDG) demonstrated increased FDG uptake in atherosclerotic plaques. Here we tested the ability of FDG-PET to measure carotid plaque inflammation in patients who subsequently underwent carotid endarterectomy (CEA). METHODS Seventeen patients with severe carotid stenoses underwent FDG-PET imaging 3 h after FDG administration (13 to 25 mCi), after which carotid plaque FDG uptake was determined as the ratio of plaque to blood activity (target to background ratio, TBR). Less than 1 month after imaging, subjects underwent CEA, after which carotid specimens were processed to identify macrophages (staining with anti-CD68 antibodies). RESULTS There was a significant correlation between the PET signal from the carotid plaques and the macrophage staining from the corresponding histologic sections (r = 0.70; p < 0.0001). When mean FDG uptake (mean TBR) was compared with mean inflammation (mean percentage CD68 staining) for each of the 17 patients, the correlation was even stronger (r = 0.85; p < 0.0001). Fluorodeoxyglucose uptake did not correlate with plaque area, plaque thickness, or area of smooth muscle cell staining. CONCLUSIONS We established that FDG-PET imaging can be used to assess the severity of inflammation in carotid plaques in patients. If subsequent natural history studies link increased FDG-PET activity in carotid arteries with clinical events, this noninvasive measure could be used to identify a subset of patients with carotid atherosclerosis in need of intensified medical therapy or carotid artery intervention to prevent stroke. C1 Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Harvard Univ, Massachusetts Gen Hosp, Div Vasc & Endovasc Surg, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Dept Med, Cardiac Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Dept Radiol & Nucl Med, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Tawakol, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Cardiac Unit, YAW 5904, Boston, MA 02114 USA. EM atawakol@partners.org FU NCRR NIH HHS [RR16046] NR 33 TC 440 Z9 451 U1 4 U2 19 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD NOV 7 PY 2006 VL 48 IS 9 BP 1818 EP 1824 DI 10.1016/j.jacc.2006.05.076 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 102IO UT WOS:000241804400015 PM 17084256 ER PT J AU Hoshijima, M Knoll, R Pashmforoush, M Chien, KR AF Hoshijima, Masahiko Knoll, Ralph Pashmforoush, Mohammad Chien, Kenneth R. TI Reversal of calcium cycling defects in advanced heart failure - Toward molecular therapy SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article; Proceedings Paper CT Leducq Symposium on Critical Issues in Cardiovascular Research CY OCT 27, 2005 CL Paris, FRANCE SP Leducq Fdn ID MUSCLE LIM PROTEIN; DYSTROPHIN-GLYCOPROTEIN COMPLEX; FAMILIAL DILATED CARDIOMYOPATHY; HYPERTROPHIC CARDIOMYOPATHY; MUSCULAR-DYSTROPHIES; BIOMECHANICAL STRESS; CARDIAC DYSFUNCTION; ATPASE INTERACTION; VASCULAR SMOOTH; DEFICIENT MICE AB Heart failure is a growing major cause of human morbidity and mortality worldwide. A wave of new insights from diverse laboratories has begun to uncover new therapeutic strategies that affect the molecular pathways within cardiomyocytes that drive heart failure progression. Using an integrative approach that employs insights from genetic-based studies in mouse and humans and in vivo somatic gene transfer studies, we have uncovered a new link between stress signals mediated by mechanical stretch and defects in sarcoplasmic reticulum (SR) calcium cycling. An intrinsic mechanical stress sensing system is embedded in the Z disc of cardiomyocytes, and defects in stretch responses can lead to heart failure progression and associated increases in wall stress. Reversal of the chronic increases in wall stress by promoting SR calcium cycling can prevent and partially reverse heart failure progression in multiple genetic and acquired model systems of heart failure in both small and large animals. We propose that reversal of advanced heart failure is possible by targeting the defects in SR calcium cycling, which may be a final common pathway for the progression of many forms of heart failure. C1 Harvard Univ, Med Sch,Cardiovasc Res Ctr, Richard B Simches Res Ctr,Dept Cell Biol, Massachusetts Gen Hosp,Harvard Stem Cell Inst, Boston, MA 02144 USA. Univ Calif San Diego, Inst Mol Med, La Jolla, CA 92093 USA. Univ Calif San Diego, Ctr Res Biol Syst, La Jolla, CA 92093 USA. RP Chien, KR (reprint author), Harvard Univ, Med Sch,Cardiovasc Res Ctr, Richard B Simches Res Ctr,Dept Cell Biol, Massachusetts Gen Hosp,Harvard Stem Cell Inst, CPZN 3208,185 Cambridge St, Boston, MA 02144 USA. EM kchien@partners.org OI Knoll, Ralph/0000-0001-8871-112X FU NHLBI NIH HHS [HL081401] NR 62 TC 26 Z9 32 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD NOV 7 PY 2006 VL 48 IS 9 SU A BP A15 EP A23 DI 10.1016/j.jacc.2006.06.070 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 103QB UT WOS:000241900700004 PM 17084280 ER PT J AU Slopsema, RL Kooy, HM AF Slopsema, Roelf L. Kooy, Hanne M. TI Incorporation of the aperture thickness in proton pencil-beam dose calculations SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID RADIOTHERAPY; PENUMBRA AB Field-specific apertures, of sufficient range-absorbing thickness, are used in the majority of proton-therapy treatments today. In current practice, these apertures are modelled as objects of infinitesimal thickness. Such an approximation, however, is not accurate if the aperture edge is close to, or extends over, the beam axis. Practical situations in which this occurs include off-axis patch fields, small apertures, and fields shaped with a multileaf collimator. We develop an extension of the pencil-beam dose model to incorporate the aperture thickness. We derive an exact solution as well as a computationally simpler approximate implementation. The model is validated using measurements of the lateral penumbra. For a set-up with a source size of 2.76 cm, a source-to-axis distance of 227 cm, and a aperture-to-axis distance of 35 cm, the maximum increase in penumbra for a 6 cm thick aperture compared to the thin-aperture model is about 2 mm. The maximum shift in the 95% isodose contour line is larger. The overall effect depends on the aperture thickness, the position of the aperture edge and the intrinsic source size and SAD, but is fairly insensitive to aperture-to-skin distance and depth in patient. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Francis H Burr Proton Therapy Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Slopsema, RL (reprint author), Univ Florida, Proton Therapy Inst, Jacksonville, FL USA. EM slopsema@ufl.edu FU NCI NIH HHS [P01 CA21239-24] NR 12 TC 11 Z9 11 U1 0 U2 1 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 NOV 7 PY 2006 VL 51 IS 21 BP 5441 EP 5453 DI 10.1088/0031-9155/51/21/004 PG 13 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 112LZ UT WOS:000242528800004 PM 17047262 ER PT J AU Bergmeier, W Piffath, CL Goerge, T Cifuni, SM Ruggeri, ZM Ware, J Wagner, DD AF Bergmeier, Wolfgang Piffath, Crystal L. Goerge, Tobias Cifuni, Stephen M. Ruggeri, Zaverio M. Ware, Jerry Wagner, Denisa D. TI The role of platelet adhesion receptor GPIb alpha far exceeds that of its main ligand, von Willebrand factor, in arterial thrombosis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE platelets; adhesion ID IX-V COMPLEX; BERNARD-SOULIER-SYNDROME; GLYCOPROTEIN IB-ALPHA; P-SELECTIN; BETA-3-INTEGRIN-DEFICIENT MICE; MONOCLONAL-ANTIBODY; INJURED ARTERIOLES; INTEGRIN MAC-1; FACTOR-VIII; HIGH-SHEAR AB GPIb alpha binding to von Willebrand factor (VWF) exposed at a site of vascular injury is thought to be the first step in the formation of a hemostatic plug. However, our previous studies in VWF-deficient mice demonstrated delayed but not absent arterial thrombus formation, suggesting that, under these conditions, GPIb alpha may bind other ligands or that a receptor other than GPIb alpha can mediate platelet adhesion. Here, we studied thrombus formation in transgenic mice expressing GPIb alpha in which the extracellular domain was replaced by that of the human IL-4 receptor (IL4Ra/GPlb alpha-tg mice). Platelet adhesion to ferric chloride-treated mesenteric arterioles in IL4Ra/GPlba-tg mice was virtually absent in contrast to avid adhesion in WT mice. As a consequence, arterial thrombus formation was inhibited completely in the mutant mice. Our studies further show that, when infused into WT recipient mice, IL4R alpha/ GPIb alpha-tg platelets or WT platelets lacking the 45-kDa N-terminal domain of GPIb alpha failed to incorporate into growing arterial thrombi, even if the platelets were activated before infusion. Surprisingly, platelets lacking beta 3 integrins, which are unable to form thrombi on their own, incorporated efficiently into WT thrombi. Our studies provide in vivo evidence that GPIba absolutely is required for recruitment of platelets to both exposed subendothelium and thrombi under arterial flow conditions. Thus, GPIb alpha contributes to arterial thrombosis by important adhesion mechanisms independent of the binding to VWF. C1 Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Scripps Res Inst, La Jolla, CA 92037 USA. Univ Arkansas Med Sci, Dept Physiol & Biophys, Little Rock, AR 72205 USA. RP Bergmeier, W (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, Boston, MA 02115 USA. EM bergmeier@cbrinstitute.org FU NHLBI NIH HHS [HL 50545, R01 HL042846, R37 HL 41002, R37 HL041002, R01 HL050545, HL 42846, R01 HL050545-14, R37 HL042846] NR 52 TC 122 Z9 131 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 7 PY 2006 VL 103 IS 45 BP 16900 EP 16905 DI 10.1073/pnas.0608207103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 104PB UT WOS:000241969500050 PM 17075060 ER PT J AU Bansal, D Scholl, C Frohling, S McDowell, E Lee, BH Dohner, K Ernst, P Davidson, AJ Daley, GQ Zon, LI Gilliland, DG Huntly, BJP AF Bansal, Dimple Scholl, Claudia Froehling, Stefan McDowell, Elizabeth Lee, Benjamin H. Doehner, Konstanze Ernst, Patricia Davidson, Alan J. Daley, George Q. Zon, Leonard I. Gilliland, D. Gary Huntly, Brian J. P. TI Cdx4 dysregulates Hox gene expression and generates acute myeloid leukemia alone and in cooperation with Meis1a in a murine model SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE transcriptional regulation; Hox regulation; leukemogenesis; self-renewal ID HEMATOPOIETIC STEM-CELLS; BONE-MARROW-CELLS; CONSTITUTIVE ACTIVATION; HOMEODOMAIN PROTEINS; DNA-BINDING; EXPANSION; FUSION; OVEREXPRESSION; T(12/13)(P13,Q12); EMBRYOGENESIS AB HOX genes have emerged as critical effectors of leukelmogenesis, but the mechanisms that regulate their expression in leukemia are not well understood. Recent data suggest that the caudal homeobox transcription factors CDX1, CDX2, and CDX4, developmental regulators of HOX gene expression, may contribute to HOX gene dysregulation in leukemia. We report here that CDX4 is expressed normally in early hernatopoietic progenitors and is expressed aberrantly in approximate to 25% of acute myeloid leukemia (AML) patient samples. Cdx4 regulates Hox gene expression in the adult murine hernatopoietic system and dysregulates Hox genes that are implicated in leukemogenesis. Furthermore, bone marrow progenitors that are retrovirally engineered to express Cdx4 serially replate in methylcellulose cultures, grow in liquid culture, and generate a partially penetrant, long-latency AML in bone marrow transplant recipients. Coexpression of the Hox cofactor Meis1a accelerates the Cdx4 AML phenotype and renders it fully penetrant. Structure-function analysis demonstrates that leukemic transformation requires intact Cdx4 transactivation and DNA-binding domains but not the putative Pbx cofactor interaction motif. Together, these data indicate that Cdx4 regulates Hox gene expression in adult hematopoiesis and may serve as an upstream regulator of Hox gene expression in the induction of acute leukemia. Inasmuch as many human leukemias show dysregulated expression of a spectrum of HOX family members, these collective findings also suggest a central role for CDX4 expression in the genesis of acute leukemia. C1 Brigham & Womens Hosp, Dept Med, Div Hematol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Univ Hosp Ulm, Dept Internal Med 3, D-89081 Ulm, Germany. Dartmouth Coll Sch Med, Dept Genet, Hanover, NH 03755 USA. Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Cambridge, Cambridge Inst Med Res, Dept Haematol, Cambridge CB2 2XY, England. RP Gilliland, DG (reprint author), Brigham & Womens Hosp, Dept Med, Div Hematol, Boston, MA 02115 USA. EM ggilliland@rics.bwh.harvard.edu; bjph2@cam.ac.uk RI huntly, brian/E-6725-2014 OI huntly, brian/0000-0003-0312-161X FU Medical Research Council [G116/187]; NCI NIH HHS [CA 66996, P01 CA066996]; NHLBI NIH HHS [HL 48801, R01 HL048801]; NIDDK NIH HHS [DK 50654, P01 DK050654] NR 39 TC 53 Z9 61 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 7 PY 2006 VL 103 IS 45 BP 16924 EP 16929 DI 10.1073/pnas.0604579103 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 104PB UT WOS:000241969500054 PM 17068127 ER PT J AU Rayner, TF Rocca-Serra, P Spellman, PT Causton, HC Farne, A Holloway, E Irizarry, RA Liu, JM Maier, DS Miller, M Petersen, K Quackenbush, J Sherlock, G Stoeckert, CJ White, J Whetzel, PL Wymore, F Parkinson, H Sarkans, U Ball, CA Brazma, A AF Rayner, Tim F. Rocca-Serra, Philippe Spellman, Paul T. Causton, Helen C. Farne, Anna Holloway, Ele Irizarry, Rafael A. Liu, Junmin Maier, Donald S. Miller, Michael Petersen, Kjell Quackenbush, John Sherlock, Gavin Stoeckert, Christian J., Jr. White, Joseph Whetzel, Patricia L. Wymore, Farrell Parkinson, Helen Sarkans, Ugis Ball, Catherine A. Brazma, Alvis TI A simple spreadsheet-based, MIAME-supportive format for microarray data: MAGE-TAB SO BMC BIOINFORMATICS LA English DT Editorial Material ID GENE-EXPRESSION DATA; INFORMATION; EXCHANGE AB Background: Sharing of microarray data within the research community has been greatly facilitated by the development of the disclosure and communication standards MIAME and MAGE-ML by the MGED Society. However, the complexity of the MAGE-ML format has made its use impractical for laboratories lacking dedicated bioinformatics support. Results: We propose a simple tab-delimited, spreadsheet-based format, MAGE-TAB, which will become a part of the MAGE microarray data standard and can be used for annotating and communicating microarray data in a MIAME compliant fashion. Conclusion: MAGE-TAB will enable laboratories without bioinformatics experience or support to manage, exchange and submit well-annotated microarray data in a standard format using a spreadsheet. The MAGE-TAB format is self-contained, and does not require an understanding of MAGE-ML or XML. C1 European Bioinformat Inst, Cambridge, England. Lawrence Berkeley Natl Lab, Berkeley, CA USA. Ctr Clin Sci, Fac Med, MRC, London, England. Johns Hopkins Univ, Sch Publ Hlth, Dept Biostat, Baltimore, MD USA. Univ Penn, Sch Med, Ctr Bioinformat, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. Stanford Univ, Sch Med, Dept Biochem, Stanford, CA 94305 USA. Rosetta Inpharmat LLC, Rosetta Biosoftware, Seattle, WA USA. Univ Bergen, Bergen Ctr Computat Sci, Computat Biol Unit, N-5020 Bergen, Norway. Dana Farber Canc Inst, Boston, MA 02115 USA. Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA. RP Rayner, TF (reprint author), European Bioinformat Inst, Wellcome Trust Genome Campus, Cambridge, England. EM rayner@ebi.ac.uk; rocca@ebi.ac.uk; ptspellman@lbl.gov; helen.causton@csc.mrc.ac.uk; farne@ebi.ac.uk; ele@ebi.ac.uk; ririzarr@jhsph.edu; junmin@pcbi.upenn.edu; dmaier@genome.stanford.edu; Michael_Miller@Rosettabio.com; Kjell.Petersen@bccs.uib.no; johnq@jimmy.harvard.edu; sherlock@genome.stanford.edu; stoeckrt@pcbi.upenn.edu; jwhite@jimmy.harvard.edu; whetzel@pcbi.upenn.edu; wymore@genome.stanford.edu; parkinso@ebi.ac.uk; ugis@ebi.ac.uk; ball@genome.stanford.edu; brazma@ebi.ac.uk RI Sherlock, Gavin/B-1831-2009; Sherlock, Gavin/E-9110-2012; OI Parkinson, Helen/0000-0003-3035-4195; Sarkans, Ugis/0000-0001-9227-8488; Sherlock, Gavin/0000-0002-1692-4983; Rayner, Tim/0000-0002-6992-5592; Brazma, Alvis/0000-0001-5988-7409 FU NHGRI NIH HHS [P41HG003619-01, R01 HG003469, P41 HG003619] NR 18 TC 103 Z9 104 U1 0 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD NOV 6 PY 2006 VL 7 AR 489 DI 10.1186/1471-2105-7-489 PG 18 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 114BX UT WOS:000242642800001 PM 17087822 ER PT J AU Fahey, JM Pritchard, GA Reddi, JM Pratt, JS Grassi, JM Shader, RI Greenblatt, DJ AF Fahey, Jeanne M. Pritchard, Gary A. Reddi, Jyoti M. Pratt, John S. Grassi, Jeffrey M. Shader, Richard I. Greenblatt, David J. TI The effect of chronic lorazepam administration in aging mice SO BRAIN RESEARCH LA English DT Article DE behavior; benzodiazepine; GABA; in situ hybridization histochemistry; lorazepam; pentylenetetrazole-induced seizure ID SUBUNIT MESSENGER-RNA; A-RECEPTOR SUBUNIT; RAT CEREBRAL-CORTEX; GABA(A) RECEPTOR; AGED RATS; SEIZURE THRESHOLD; BENZODIAZEPINE HYPNOTICS; EXPRESSION CHANGES; CHLORIDE UPTAKE; DOWN-REGULATION AB To assess benzodiazepine tolerance in aged animals, lorazepam or vehicle was administered chronically to male Crl: CD-1(ICR)BR mice. Pharmacodynamic and neurochemical endpoints were examined on days 1 and 14 of drug administration. There was no age-related significant difference in plasma lorazepam levels. Young and middleaged animals demonstrated behavioral tolerance to lorazepam, while the aged animals showed a similar trend which failed to reach significance. in addition, aged animals also showed a trend toward tolerance to the anticonvulsant effects of lorazepam. There were no changes in alpha 1 mRNA levels in cortex orhippocampus following administration of lorazepam when compared to vehicle-treated animals in any age group. Aged animals, however, had an initial increase in al mRNA expression in cortex and hippocampus on day I of vehicle treatment followed by decreased expression on day 14. These age-related changes were abolished by lorazepam administration. In summary, age-related sensitivity to the effects of lorazepam was not demonstrated in the present study. However, comparison of these data to other studies indicates that the effect of chronic benzodiazepine treatment may be specific to the benzodiazepine administered, the technique used to quantify mRNA expression changes, the subunits of the GABA(A) receptor investigated and the brain region analyzed. The phenomenon of benzodiazepine sensitivity in the elderly is an area of research which remains controversial and may well be compound specific. Determining benzodiazepines that do not produce pharmacodynamic sensitivity, such as lorazepam, may allow more careful prescribing and dosing of these drugs, and perhaps even the development of specific agents which could avoid this sensitivity. (c) 2006 Elsevier B.V. All rights reserved. C1 Tufts Univ, Sch Med, Dept Pharmacol & Expt Therapeut, Boston, MA 02111 USA. Tufts Univ, New England Med Ctr, Div Clin Pharmacol, Boston, MA 02111 USA. Harvard Apparatus Inc, Hugo Sachs Elektron Solut Physiol, Holliston, MA 01746 USA. Massachusetts Gen Hosp, Div Neuroradiol, MGH NMR Ctr, Boston, MA 02111 USA. Harvard Univ, Sch Med, Boston, MA 02111 USA. Vertex Pharmaceut Incorp, Cambridge, MA 02139 USA. RP Fahey, JM (reprint author), Tufts Univ, Sch Med, Dept Pharmacol & Expt Therapeut, 136 Harrison Ave, Boston, MA 02111 USA. EM Jeanne.fahey@tufts.edu OI Shader, Richard/0000-0002-1888-7565 FU NIAID NIH HHS [AI-58784]; NIDA NIH HHS [DA-05258, DA-13834, DA-13209]; NIDDK NIH HHS [DK-58496]; NIMH NIH HHS [MH-58435] NR 83 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 EI 1872-6240 J9 BRAIN RES JI Brain Res. PD NOV 6 PY 2006 VL 1118 BP 13 EP 24 DI 10.1016/j.brainres.2006.08.017 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 107CD UT WOS:000242147400003 PM 16989785 ER PT J AU Garg, HG Hales, CA Yu, LY Butler, M Islam, T Xie, J Linhardt, RJ AF Garg, Hari G. Hales, Charles A. Yu, Lunyin Butler, Melissa Islam, Tasneem Xie, Jin Linhardt, Robert J. TI Increase in the growth inhibition of bovine pulmonary artery smooth muscle cells by an O-hexanoyl low-molecular-weight heparin derivative SO CARBOHYDRATE RESEARCH LA English DT Article DE O-hexanoyl heparin; pulmonary artery smooth muscle cell proliferation ID TERMINALLY ALKYLATED HEPARIN; CELLULAR PROLIFERATION; BINDING-SITE; KINETICS; HYPOXIA; INVITRO; INJURY; RATS AB Proliferation of pulmonary artery smooth muscle cells (PASMCs) appears to play a significant role in chronic pulmonary hypertension. The proliferation of PASMCs is strongly inhibited by some commercial heparin preparations. Heparin fragments were prepared by periodate treatment, followed by sodium borohydride reduction, to enhance potency. The tributylammonium salt of this fragmented heparin was O-acylated with hexanoic anhydride. Gradient polyacrylamide gel electrophoresis showed that the major heparin fragment contained eight disaccharide units. NMR analysis showed that approximately one hexanoyl group per disaccharide residue was present. The O-hexanoyl heparin fragments were assayed for growth inhibitory effect on bovine PASMCs in culture. This derivative was found to be more effective in growth inhibition of bovine PASMCs in culture than the heparin from which it was derived. In the future, it is envisioned that this or similar derivatives may be an effective treatment for pulmonary hypertension. (c) 2006 Elsevier Ltd. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pulm Crit Care Unit, Boston, MA 02114 USA. Univ Iowa, Dept Chem, Div Med & Nat Prod Chem, Iowa City, IA 52242 USA. Rensselaer Polytech Inst, Biotechnol Ctr 4005, Dept Chem & Biol Chem, Troy, NY 12180 USA. Rensselaer Polytech Inst, Biotechnol Ctr 4005, Dept Biol & Chem Engn, Troy, NY 12180 USA. RP Garg, HG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pulm Crit Care Unit, Boston, MA 02114 USA. EM hgarg@partners.org FU NHLBI NIH HHS [R01 HL052622, R01 HL039150, R01 HL052622-09]; NIGMS NIH HHS [R01 GM038060, R01 GM038060-19] NR 22 TC 8 Z9 9 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0008-6215 J9 CARBOHYD RES JI Carbohydr. Res. PD NOV 6 PY 2006 VL 341 IS 15 BP 2607 EP 2612 DI 10.1016/j.carres.2006.07.014 PG 6 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 097KH UT WOS:000241445600017 PM 16920092 ER PT J AU Coyle, TR Kochunov, P Patel, RD Nery, FG Lancaster, JL Mangin, JF Riviere, D Pillow, DR Davis, GJ Nicoletti, MA Monkul, ES Fox, PT Soares, JC AF Coyle, Thomas R. Kochunov, Peter Patel, Rupal D. Nery, Fabiano G. Lancaster, Jack L. Mangin, Jean-Francois Riviere, Denis Pillow, David R. Davis, Gregory J. Nicoletti, Mark A. Monkul, E. Serap Fox, Peter T. Soares, Jair C. TI Cortical sulci and bipolar disorder SO NEUROREPORT LA English DT Article DE bipolar disorder; brain; cortical sulci; diagnostic imaging; magnetic resonance imaging; sulcal width ID MOOD DISORDERS; BRAIN; SCHIZOPHRENIA; MORPHOMETRY; VOLUMES; CORTEX; MATTER AB The width of cortical sulci in bipolar patients (n = 19) and healthy controls (n = 35) was examined using a novel automated technique involving magnetic resonance imaging. All sulci were wider for bipolar patients than for healthy controls. Bipolar-control differences were largest for the superior and intermediate frontal sulci, smallest for the occipital and cingulate sulci, and intermediate in magnitude for the other sulci (intraparietal, inferior frontal, and central sulci). The results were interpreted in terms of neurodegenerative-illness-related processes, which could produce cortical atrophy and result in wider sulci. C1 Univ Texas, Dept Psychol, San Antonio, TX 78249 USA. Univ Texas, Hlth Sci Ctr, Res Imaging Ctr, San Antonio, TX 78249 USA. Univ Texas, Hlth Sci Ctr, MOOD CNS Program, Dept Psychiat,Div Mood & Anxiety Disorders, San Antonio, TX 78249 USA. S Texas Vet Hlth Care Syst, Audie L Murphy Div, San Antonio, TX USA. Univ Sao Paulo, Sch Med, Dept Psychiat, BR-05508 Sao Paulo, Brazil. Commissariat Energie Atom, Serv Hosp Frederic Joliot, Orsay, France. Dokuz Eylul Univ, Sch Med, Dept Psychiat, Izmir, Turkey. RP Coyle, TR (reprint author), Univ Texas, Dept Psychol, 1 UTSA Circle, San Antonio, TX 78249 USA. EM Thomas.Coyle@utsa.edu RI Lancaster, Jack/F-2994-2010; Kochunov, Peter/E-4711-2010; Fox, Peter/B-4725-2010 OI Fox, Peter/0000-0002-0465-2028 FU NCRR NIH HHS [M01-RR-01346, RR 20571]; NIDA NIH HHS [P20 MH/DA52176]; NIMH NIH HHS [MH 69774, MH 68662, MH 68766] NR 21 TC 11 Z9 11 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD NOV 6 PY 2006 VL 17 IS 16 BP 1739 EP 1742 DI 10.1097/01.wnr.0000239957.53072.f0 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 104MG UT WOS:000241961900016 PM 17047464 ER PT J AU Joukov, V Groen, AC Prokhorova, T Gerson, R White, E Rodriguez, A Walter, JC Livingston, DM AF Joukov, Vladimir Groen, Aaron C. Prokhorova, Tatyana Gerson, Ruth White, Erinn Rodriguez, Alison Walter, Johannes C. Livingston, David M. TI The BRCA1/BARD1 heterodimer modulates ran-dependent mitotic spindle assembly SO CELL LA English DT Article ID BRCA1 TUMOR-SUPPRESSOR; SMALL GTPASE RAN; CANCER SUSCEPTIBILITY; UBIQUITIN-LIGASE; EGG EXTRACTS; RING FINGER; CELL; XENOPUS; BREAST; CENTROSOME AB The heterodimeric tumor-suppressor complex BRCA1/BARD1 exhibits E3 ubiquitin ligase activity and participates in cell proliferation and chromosome stability control by incompletely defined mechanisms. Here we show that, in both mammalian cells and Xenopus egg extracts, BRCA1/BARD1 is required for mitotic spindle-pole assembly and for accumulation of TPX2, a major spindle organizer and Ran target, on spindle poles. This function is centrosome independent, operates downstream of Ran GTPase, and depends upon BRCA1/BARD1 E3 ubiquitin ligase activity. Xenopus BRCA1/BARD1 forms endogenous complexes with three spindle-pole proteins, TPX2, NuMA, and XRHAMM-a known TPX2 partner-and specifically attenuates XRHAMM function. These observations reveal a previously unrecognized function of BRCA1/BARD1 in mitotic spindle assembly that likely contributes to its role in chromosome stability control and tumor suppression. C1 Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Walter, JC (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, 240 Longwood Ave, Boston, MA 02115 USA. EM johannes_walter@hms.harvard.edu; david_livingston@dfci.harvard.edu OI Gerson, Ruth/0000-0002-7987-0206 FU NIGMS NIH HHS [GM62267] NR 46 TC 164 Z9 167 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD NOV 3 PY 2006 VL 127 IS 3 BP 539 EP 552 DI 10.1016/j.cell.2006.08.053 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 104DS UT WOS:000241937000018 PM 17081976 ER PT J AU Cho, YH Yoo, SD Sheen, J AF Cho, Young-Hee Yoo, Sang-Dong Sheen, Jen TI Regulatory functions of nuclear hexokinase1 complex in glucose signaling SO CELL LA English DT Article ID YEAST SACCHAROMYCES-CEREVISIAE; CARBON CATABOLITE REPRESSION; VACUOLAR H+-ATPASE; GENE-EXPRESSION; ARABIDOPSIS-THALIANA; HIGHER-PLANTS; PROTEASOME; PROTEIN; GLUCOKINASE; PROMOTER AB Arabidopsis hexokinase1 (HXK1) is a glucose sensor that integrates nutrient and hormone signals to govern gene expression and plant growth in response to environmental cues. How the metabolic enzyme mediates glucose signaling remains a mystery. By coupling proteomic and binary-interaction screens, we discover two nuclear-specific HXK1 unconventional partners: the vacuolar H+-ATPase B1 (VHA-B1) and the 19S regulatory particle of proteasome subunit (RPT5B). Remarkably, vha-B1 and rpt5b mutants uniquely share a broad spectrum of glucose response defects with the HXK1 mutant gin2 (glucose-insensitive2). Genetic and chromatin immunoprecipitation analyses suggest that the nuclear HXK1 forms a glucose signaling complex core with VHA-B1 and RPT5B that directly modulates specific target gene transcription independent of glucose metabolism. The findings support a model in which conserved metabolic enzymes and proteins of well-established activities may perform previously unrecognized nuclear functions. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Genet,Dept Mol Biol, Boston, MA 02114 USA. RP Sheen, J (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Genet,Dept Mol Biol, Boston, MA 02114 USA. EM sheen@molbio.mgh.harvard.edu FU NIGMS NIH HHS [R01 GM060493] NR 49 TC 201 Z9 216 U1 5 U2 29 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD NOV 3 PY 2006 VL 127 IS 3 BP 579 EP 589 DI 10.1016/j.cell.2006.09.028 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 104DS UT WOS:000241937000021 PM 17081979 ER PT J AU Lepilina, A Coon, AN Kikuchi, K Holdway, JE Roberts, RW Burns, CG Poss, KD AF Lepilina, Alexandra Coon, Ashley N. Kikuchi, Kazu Holdway, Jennifer E. Roberts, Richard W. Burns, C. Geoffrey Poss, Kenneth D. TI A dynamic epicardial injury response supports progenitor cell activity during zebrafish heart regeneration SO CELL LA English DT Article ID RED FLUORESCENT PROTEIN; STEM-CELLS; CARDIOVASCULAR-SYSTEM; TRANSCRIPTION FACTORS; VASCULAR DEVELOPMENT; LIVER-REGENERATION; HEMATOPOIETIC STEM; LIMB REGENERATION; FIN REGENERATION; AVIAN HEART AB Zebrafish possess a unique yet poorly understood capacity for cardiac regeneration. Here, we show that regeneration proceeds through two coordinated stages following resection of the ventricular apex. First a blastema is formed, comprised of progenitor cells that express precardiac markers, undergo differentiation, and proliferate. Second, epicardial tissue surrounding both cardiac chambers induces developmental markers and rapidly expands, creating a new epithelial cover for the exposed myocardium. A subpopulation of these epicardial cells undergoes epithelial-to-mesenchymal transition (EMT), invades the wound, and provides new vasculature to regenerating muscle. During regeneration, the ligand fgf17b is induced in myocardium, while receptors fgfr2 and fgfr4 are induced in adjacent epicardial-derived cells. When fibroblast growth factors (Fgf) signaling is experimentally blocked by expression of a dominant-negative Fgf receptor, epicardial EMT and coronary neovascularization fail, prematurely arresting regeneration. Our findings reveal injury responses by myocardial and epicardial tissues that collaborate in an Fgf-dependent manner to achieve cardiac regeneration. C1 Duke Univ, Med Ctr, Dept Cell Biol, Durham, NC 27710 USA. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Charlestown, MA 02129 USA. RP Poss, KD (reprint author), Duke Univ, Med Ctr, Dept Cell Biol, Durham, NC 27710 USA. EM k.poss@cellbio.duke.edu RI Kikuchi, Kazu/A-4097-2017 OI Kikuchi, Kazu/0000-0002-4681-4275 FU NIA NIH HHS [K01 AG023562] NR 53 TC 371 Z9 383 U1 7 U2 50 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 EI 1097-4172 J9 CELL JI Cell PD NOV 3 PY 2006 VL 127 IS 3 BP 607 EP 619 DI 10.1016/j.cell.2006.08.052 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 104DS UT WOS:000241937000023 PM 17081981 ER PT J AU Nojiri, H Shimizu, T Funakoshi, M Yamaguchi, O Zhou, H Kawakami, S Ohta, Y Sami, M Tachibana, T Ishikawa, H Kurosawa, H Kahn, RC Otsu, K Shirasawa, T AF Nojiri, Hidetoshi Shimizu, Takahiko Funakoshi, Masabumi Yamaguchi, Osamu Zhou, Heying Kawakami, Satoru Ohta, Yutaka Sami, Manabu Tachibana, Toshiaki Ishikawa, Hiroshi Kurosawa, Hisashi Kahn, Ronald C. Otsu, Kinya Shirasawa, Takuji TI Oxidative stress causes heart failure with impaired mitochondrial respiration SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MANGANESE SUPEROXIDE-DISMUTASE; DILATED CARDIOMYOPATHY; MYOCARDIAL-INFARCTION; GENE-EXPRESSION; MUTANT MICE; LIFE-SPAN; IN-VIVO; OXYGEN; APOPTOSIS; PROTEIN AB Elderly people insidiously manifest the symptoms of heart failure, such as dyspnea and/or physical disabilities in an age-dependent manner. Although previous studies suggested that oxidative stress plays a pathological role in the development of heart failure, no direct evidence has been documented so far. In order to investigate the pathological significance of oxidative stress in the heart, we generated heart/muscle-specific manganese superoxide dismutase-deficient mice. The mutant mice developed progressive congestive heart failure with specific molecular defects in mitochondrial respiration. In this paper, we showed for the first time that the oxidative stress caused specific morphological changes of mitochondria, excess formation of superoxide (O-2(center dot)), reduction of ATP, and transcriptional alterations of genes associated with heart failure in respect to cardiac contractility. Accordingly, administration of a superoxide dismutase mimetic significantly ameliorated the symptoms. These results implied that O-2(center dot) generated in mitochondria played a pivotal role in the development and progression of heart failure. We here present a bona fide model for human cardiac failure with oxidative stress valuable for therapeutic interventions. C1 Tokyo Metropolitan Inst Gerontol, Res Team Mol Biomarkers, Itabashi Ku, Tokyo 1730015, Japan. Juntendo Univ, Sch Med, Dept Orthoped, Bunkyo Ku, Tokyo 1138421, Japan. Tokyo Metropolitan Univ, Grad Sch Sci, Hachioji, Tokyo 1920397, Japan. Osaka Univ, Grad Sch Med, Suita, Osaka 5650871, Japan. Asahi Brewery Co Ltd, Fundamental Res Lab, Moriya, Ibaraki 3020106, Japan. Jikei Univ, Sch Med, Dept Anat 2, Minato Ku, Tokyo 1058461, Japan. Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. Tokyo Univ Agr & Technol, United Grad Sch Agr Sci, Fuchu, Tokyo 1838509, Japan. Anti Aging Sci Inc, Chiyoda Ku, Tokyo 1000001, Japan. RP Shirasawa, T (reprint author), Tokyo Metropolitan Inst Gerontol, Res Team Mol Biomarkers, Itabashi Ku, 35-2 Sakaesho, Tokyo 1730015, Japan. EM sirasawa@tmig.or.jp NR 45 TC 109 Z9 112 U1 0 U2 8 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 3 PY 2006 VL 281 IS 44 BP 33789 EP 33801 DI 10.1074/jbc.M602118200 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 099UJ UT WOS:000241621400085 PM 16959785 ER PT J AU Inoue, K Mikuni-Takagaki, Y Oikawa, K Itoh, T Inada, M Noguchi, T Park, JS Onodera, T Krane, SM Noda, M Itohara, S AF Inoue, Keiichi Mikuni-Takagaki, Yuko Oikawa, Kaoru Itoh, Takeshi Inada, Masaki Noguchi, Takanori Park, Jin-Sung Onodera, Takashi Krane, Stephen M. Noda, Masaki Itohara, Shigeyoshi TI A crucial role for matrix metalloproteinase 2 in osteocytic canalicular formation and bone metabolism SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID IN-VITRO; MATRIX METALLOPROTEINASE-2; MULTICENTRIC OSTEOLYSIS; COLLAGENASE CLEAVAGE; BMP ANTAGONIST; NAO SYNDROME; MICE; ARTHRITIS; PROTEIN; CELLS AB Extracellular matrix production and degradation by bone cells are critical steps in bone metabolism. Mutations of the gene encoding MMP-2, an extracellular matrix-degrading enzyme, are associated with a human genetic disorder characterized by subcutaneous nodules, arthropathy, and focal osteolysis. It is not known how the loss of MMP-2 function results in the pathology. Here, we show that Mmp2(-/-) mice exhibited opposing bone phenotypes caused by an impaired osteocytic canalicular network. Mmp2(-/-) mice showed decreased bone mineral density in the limb and trunk bones but increased bone volume in the calvariae. In the long bones, there was moderate disruption of the osteocytic networks and reduced bone density throughout life, whereas osteoblast and osteoclast function was normal. In contrast, aged but not young Mmp2(-/-) mice had calvarial sclerosis with osteocyte death. Severe disruption of the osteocytic networks preceded osteocyte loss in Mmp2(-/-) calvariae. Successful transplantation of wild-type periosteum restored the osteocytic canalicular networks in the Mmp2(-/-) calvariae, suggesting local roles of MMP-2 in determining bone phenotypes. Our results indicate that MMP-2 plays a crucial role in forming and maintaining the osteocytic canalicular network, and we propose that osteocytic network formation is a determinant of bone remodeling and mineralization. C1 Tokyo Med & Dent Univ, Med Res Inst, Dept Mol Pharmacol, Chiyoda Ku, Tokyo 1010062, Japan. RIKEN, Brain Sci Inst, Lab Behav Genet, Wako, Saitama 3510198, Japan. Tokyo Med & Dent Univ, Ctr Excellence Program Mol Destruct & Reconstruct, Chiyoda Ku, Tokyo 1010062, Japan. Univ Tokyo, Grad Sch Agr & Life Sci, Dept Mol Immunol, Bunkyo Ku, Tokyo 1138657, Japan. Kanagawa Dent Coll, Dept Funct Biol, Div Biochem & Mol Biol, Kanagawa 2388580, Japan. Shionogi & Co Ltd, Discovery Res Labs, Osaka 5610825, Japan. Massachusetts Gen Hosp, Boston, MA 02129 USA. Harvard Univ, Sch Med, Dept Med, Ctr Immunol & Inflammatory Dis, Boston, MA 02129 USA. RP Itohara, S (reprint author), Tokyo Med & Dent Univ, Med Res Inst, Dept Mol Pharmacol, Chiyoda Ku, 2-3-10 Kanda Surugadai, Tokyo 1010062, Japan. EM sitohara@brain.riken.jp RI Itohara, Shigeyoshi/I-8769-2012; Park, Jin-Sung/F-9867-2011; inada, masaki/D-1581-2013; OI Itohara, Shigeyoshi/0000-0002-2410-9989; inada, masaki/0000-0002-5066-8506; Inoue, Keiichi/0000-0002-7101-486X NR 50 TC 95 Z9 100 U1 0 U2 8 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 3 PY 2006 VL 281 IS 44 BP 33814 EP 33824 DI 10.1074/jbc.M607290200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 099UJ UT WOS:000241621400087 PM 16959767 ER PT J AU Shi, Q Harris, LN Lu, X Li, XC Hwang, J Gentleman, R Iglehart, JD Miron, A AF Shi, Qian Harris, Lyndsay N. Lu, Xin Li, Xiaochun Hwang, Justin Gentleman, Robert Iglehart, J. Dirk Miron, Alexander TI Declining plasma fibrinogen alpha fragment identifies HER2-positive breast cancer patients and reverts to normal levels after surgery SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE breast cancer; proteomics; HER2; fibrinogen; plasma ID LASER DESORPTION/IONIZATION-TIME; ARTIFICIAL NEURAL-NETWORKS; SELDI MASS-SPECTROMETRY; SERUM-PROTEIN PROFILES; GENE-EXPRESSION DATA; LYMPH-NODE STATUS; OVARIAN-CANCER; BIOMARKER DISCOVERY; PROTEOMIC PATTERNS; PROSTATE-CANCER AB Breast cancer is the most common nonskin malignancy affecting women. Currently, no simple, blood-based diagnostic test exists to complement radiological screening and increase sensitivity of detection. To screen plasma specimens and identify biomarkers that detect HER2-positive breast cancer, automated robotic sample processing followed by surface-enhanced laser desorption ionization time-of-flight (SELDI-TOF) mass spectroscopy was used. Multiple statistical algorithms were used to select biomarkers that segregate cancer patients versus controls and produced average CV rates ranging from 20% to 29%. A set of seven biomarkers were validated on an independent test data set and achieved the best error rate of 19.1%. A permutation test indicateded a p-value for CV error less than 0.002. Moreover, a ROC curve using these biomarkers achieved an area-under-the-curve value of 0.95 on an independent test data set. The marker responsible for most of the resolving power was identified as a fragment of Fibrinogen Alpha (FGA) encompassing residues 605-629. This marker was present at lower levels in cancer patients as compared to controls. The importance of this biomarker was validated in a longitudinal study comparing pre- and post-operative levels and was shown to revert to normal levels after surgery. This fragment may serve as a useful diagnostic and treatment-monitoring marker. C1 Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Fudan Univ, Inst Prote & Syst Biol, Inst Biomed Sci, Shanghai 200433, Peoples R China. Univ Calif San Diego, Dept Family & Prevent Med, San Diego, CA 92103 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Fred Hutchinson Canc Res Ctr, Program Computat Biol, Seattle, WA 98104 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. RP Miron, A (reprint author), Dana Farber Canc Inst, Dept Canc Biol, 44 Binney St, Boston, MA 02115 USA. EM alexander_miron@dfci.harvard.edu FU NCI NIH HHS [5 P50 CA089393] NR 56 TC 24 Z9 27 U1 1 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1535-3893 J9 J PROTEOME RES JI J. Proteome Res. PD NOV 3 PY 2006 VL 5 IS 11 BP 2947 EP 2955 DI 10.1021/pr060099u PG 9 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 101QL UT WOS:000241755400008 PM 17081046 ER PT J AU Wang, S Yao, Z Wang, J Ai, Y Li, D Zhang, Y Mao, J Gu, H Ruan, Y Mao, J AF Wang, S. Yao, Z. Wang, J. Ai, Y. Li, D. Zhang, Y. Mao, J. Gu, H. Ruan, Y. Mao, J. TI Evidence for a distinct group of nestin-immunoreactive neurons within the basal forebrain of adult rats SO NEUROSCIENCE LA English DT Article DE nestin; cholinergic; GABAergic; colocalization; immunohistochemistry; basal forebrain ID CENTRAL-NERVOUS-SYSTEM; NEURAL STEM-CELLS; INTERMEDIATE FILAMENT PROTEIN; FOCAL CEREBRAL-ISCHEMIA; CHOLINE-ACETYLTRANSFERASE; GABAERGIC NEURONS; DIAGONAL BAND; MEDIAL SEPTUM; MAMMALIAN FOREBRAIN; SUBVENTRICULAR ZONE AB Nestin is an intermediate filament protein serving as a marker for neuroprogenitor and stem cells. Here we report that a cluster of previously unrecognized nestin immunoreactive (nestin-ir) neurons was located in the medial septum-diagonal band of Broca (MS-DBB) of the basal forebrain in adult rats. Nestin-ir neurons were exclusively located in the MS-DBB and intermingled with choline acetyltransferase-ir (ChAT-ir), parvalbumin-ir (PV-ir), or nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase reactive (NADPHd-reactive) neurons. However, there was no colocalization between nestin-ir and PV-ir in single neurons in MS-DBB; only about 35% of nestin-ir neurons were ChAT-ir, and 8%-12% of nestin-ir neurons were NADPHd-reactive. Morphologically, nestin-ir neurons showed a larger size of somata than that of ChAT-ir or PV-ir neurons and the distribution of nestin-ir neurons spread across the rostro-caudal extent of the MS-DBB. Moreover, retrograde tracing revealed that a significant portion of these nestin-ir neurons projected to the thalamus and hippocampus. These results, for the first time, provide strong evidence that there exists a cluster of previously unrecognized nestin-ir neurons in MS-DBB of the basal forebrain in adult rats and that these nestin-ir neurons are distinguishable from ChAT-ir, PV-ir, and NADPHd-reactive neurons. (c) 2006 IBRO. Published by Elsevier Ltd. All rights reserved. C1 Sun Yat Sen Univ, Zhongshan Med Coll, Dept Anat & Neurobiol, Guangzhou 510080, Peoples R China. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care,Pain Res Grp, Boston, MA 02114 USA. RP Yao, Z (reprint author), Sun Yat Sen Univ, Zhongshan Med Coll, Dept Anat & Neurobiol, 74 Zhongshan 2nd Rd, Guangzhou 510080, Peoples R China. EM yao.zb@163.com FU NINDS NIH HHS [NS45681, NS42661] NR 65 TC 12 Z9 17 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 EI 1873-7544 J9 NEUROSCIENCE JI Neuroscience PD NOV 3 PY 2006 VL 142 IS 4 BP 1209 EP 1219 DI 10.1016/j.neuroscience.2006.07.059 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 104AA UT WOS:000241927100024 PM 16997483 ER PT J AU Martin, SI Wilkinson, R Fishman, JA AF Martin, Stanley I. Wilkinson, Robert Fishman, Jay A. TI Genomic presence of recombinant porcine endogenous retrovirus in transmitting miniature swine SO VIROLOGY JOURNAL LA English DT Article ID NO EVIDENCE; HUMAN-CELLS; INFECTION; TRANSMISSION; DNA AB The replication of porcine endogenous retrovirus (PERV) in human cell lines suggests a potential infectious risk in xenotransplantation. PERV isolated from human cells following cocultivation with porcine peripheral blood mononuclear cells is a recombinant of PERV-A and PERV-C. We describe two different recombinant PERV-AC sequences in the cellular DNA of some transmitting miniature swine. This is the first evidence of PERV-AC recombinant virus in porcine genomic DNA that may have resulted from autoinfection following exogenous viral recombination. Infectious risk in xenotransplantation will be defined by the activity of PERV loci in vivo. C1 Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Fishman, JA (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. EM simartin100@gmail.com; rwilkinson@partners.org; jfishman@partners.org RI Martin, Stanley/E-3600-2011 FU NIAID NIH HHS [P01 AI045897, 5T32-AI07529, P01-AI45897, T32 AI007529] NR 12 TC 30 Z9 30 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1743-422X J9 VIROL J JI Virol. J. PD NOV 2 PY 2006 VL 3 AR 91 DI 10.1186/1743-422X-3-91 PG 6 WC Virology SC Virology GA 182NA UT WOS:000247510100002 PM 17081300 ER PT J AU Gilbert, S Zheng, B Leader, JK Luketich, JD Fuhrman, CR Landreneau, RJ Gur, D Sciurba, FC AF Gilbert, Sebastien Zheng, Bin Leader, Joseph K. Luketich, James D. Fuhrman, Carl R. Landreneau, Rodney J. Gur, David Sciurba, Frank C. TI Computerized estimation of the lung volume removed during lung volume reduction surgery SO ACADEMIC RADIOLOGY LA English DT Article DE lung volume reduction surgery; computed tomography; emphysema; CT densitomtery ID SEVERE EMPHYSEMA; PULMONARY-FUNCTION; DIFFUSE EMPHYSEMA; QUANTITATIVE CT; CLINICAL-TRIAL; RABBIT MODEL; DISEASE; IMPROVEMENT; TOMOGRAPHY AB Rationale and Objectives. This study was designed to develop an automated method for estimating lung volume removed during lung volume reduction surgery (LVRS) using computed tomography (CT). Materials and Methods. The CT examinations of six patients who underwent bilateral LVRS were analyzed in this study. The resected lung tissue (right and left) was weighed during pathologic examination. An automated computer scheme was developed to estimate the lung volume removed using the CT voxel values and lung specimen weight. The computed fraction of lung volume removed was evaluated across a range of simulated surgical planes (ie, other than parallel to the CT image plane) and CT reconstruction kernels, and it was compared with the surgeons' postsurgical estimates. Results. The computed fraction of the lung volume removed during LVRS was linearly correlated with the resected lung tissue weight (Pearson correlation = 0.697, P =.012). The computed fraction of lung volume removed ranged from 12.9% to 51.7% of the total lung volume. The surgeons' postsurgical estimates of lung volume removed ranged from 30% to 33%. The percent difference between the surgeons' estimates and the computed lung volume removed as a percentage of the surgeons' estimates ranged from -72.3% to 57.0% with mean absolute difference of 29.7% (+/- 20.7). Conclusion. The preliminary findings of this study suggest that the proposed quantitative model should provide an objective measure of lung volume removed during LVRS that may be used to investigate the relationship between lung volume removed and outcome. C1 Univ Pittsburgh, Imaging Res Div, Dept Radiol, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Imaging Res Div, Dept Surg, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Imaging Res Div, Dept Med, Pittsburgh, PA 15213 USA. Vet Affairs Pittsburgh Hlth Syst, Pittsburgh, PA 15240 USA. RP Leader, JK (reprint author), Univ Pittsburgh, Imaging Res Div, Dept Radiol, 300 Halket St,Suite 4200, Pittsburgh, PA 15213 USA. EM leaderjk@upmc.edu OI Gilbert, Sebastien/0000-0003-4357-9553; Zheng, Bin/0000-0002-7682-6648 NR 33 TC 1 Z9 2 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 NOV PY 2006 VL 13 IS 11 BP 1379 EP 1386 DI 10.1016/j.acra.2006.08.013 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 106PY UT WOS:000242114400009 PM 17070456 ER PT J AU Kleinschmidt-DeMasters, BK Filley, CM Rojiani, AM AF Kleinschmidt-DeMasters, B. K. Filley, Christopher M. Rojiani, Amyn M. TI Overlapping features of extrapontine myelinolysis and acquired chronic (non-Wilsonian) hepatocerebral degeneration SO ACTA NEUROPATHOLOGICA LA English DT Article DE central pontine myelinolysis; osmotic demyelination; hyponatremia; chronic alcoholism; lateral pontine myelinolysis; extrapontine myelinolysis; pathogenesis; liver failure; U-fibers; arcuate fibers ID CENTRAL PONTINE MYELINOLYSIS; ELECTROLYTE-INDUCED DEMYELINATION; RAPID CORRECTION; HYPONATREMIA; RATS AB Central pontine myelinolysis (CPM, osmotic demyelination syndrome) and acquired chronic hepatocerebral degeneration (ACHD) both occur in patients with liver failure, but are not thought to be caused by similar etiopathogenic mechanisms despite the fact that occasional patients exhibit both disorders. In our autopsy practice we have recently encountered three patients with the pontine lesions of acute or subacute osmotic demyelination syndrome, coupled with superimposed non-Wilsonian ACHD. All three patients had well-documented rapid elevations in serum sodium proximate to their demise, as well as terminal liver failure. A close intermingling and juxtaposition of lesions with severe demyelination and macrophage breakdown [thought to represent extrapontine myelinolysis (EPM)] to those with vacuolization of myelin but no cellular reaction or myelin loss (ACHD) was noted within some of the same anatomic areas. Particular overlap was seen in lesions at the cerebral cortical gray-white junction and in pencil fibers of the striatum. In these areas it was difficult to be certain whether the lesions were due to EPM or ACHD. We concluded that there was a synergism between the two disorders and raise the possibility that there may be factors common to both disorders that lead to similar anatomic sites for involvement. C1 Univ Colorado Denver & Hlth Sci Ctr, Dept Pathol, Denver, CO 80262 USA. Univ Colorado Denver & Hlth Sci Ctr, Dept Neurol, Denver, CO 80262 USA. Univ Colorado Denver & Hlth Sci Ctr, Dept Psychiat, Denver, CO 80262 USA. Univ Colorado Denver & Hlth Sci Ctr, Dept Neurosurg, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Denver, CO USA. Univ S Florida, Dept Interdisciplinary Oncol & Pathol Neuropathol, Tampa, FL USA. RP Kleinschmidt-DeMasters, BK (reprint author), Univ Colorado Denver & Hlth Sci Ctr, Dept Pathol, 4200 E 9th Ave,B-216, Denver, CO 80262 USA. EM BK.DeMasters@uchsc.edu NR 24 TC 8 Z9 10 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0001-6322 J9 ACTA NEUROPATHOL JI Acta Neuropathol. PD NOV PY 2006 VL 112 IS 5 BP 605 EP 616 DI 10.1007/s00401-006-0112-6 PG 12 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 094RR UT WOS:000241257200009 PM 16871403 ER PT J AU Oursler, KK Goulet, JL Leaf, DA Akingicil, A Katzel, LI Justice, A Crystal, S AF Oursler, Krisann K. Goulet, Joseph L. Leaf, David A. Akingicil, Ayse Katzel, Leslie I. Justice, Amy Crystal, Stephen TI Association of comorbidity with physical disability in older HIV-infected adults SO AIDS PATIENT CARE AND STDS LA English DT Article ID QUALITY-OF-LIFE; HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; HEPATITIS-C VIRUS; FUNCTIONAL STATUS; HEALTH; VETERANS; DISEASE; COHORT; HAART AB Comorbidity, aging, and their impact on physical functioning will play an increasingly greater role in HIV medical care as the number of infected adults over 50 years of age grows. The study objective was to investigate the relationship of comorbidity and age with physical functioning in HIV-infected and HIV-negative patients. Eight hundred eighty-nine HIV-infected veterans and 647 HIV-negative veterans from the Veterans Aging Cohort Study conducted between September 2001 and June 2002 were included in the study. Physical functioning was measured by self-reported difficulty with various physical activities. Regression analyses were performed to examine demographic and clinical factors associated with physical functioning. Separate models were used for HIV-infected and HIV negative subjects since these groups differed in demographic makeup. In both patient groups, chronic lung disease, coronary artery disease, hypertension, smoking, and major depression were independently associated with reduced physical functioning in age and race adjusted regression models. Increased age was associated with reduced physical functioning in both HIV-infected and HIV-negative patients. However, when comorbid conditions were entered into the models for both HIV-infected and HIV-negative patients, age coefficients were reduced and were no longer statistically significant. Among the HIV-infected patients, results remained unchanged after controlling for the impact of antiretroviral therapy and HIV disease stage. Our findings demonstrate the important role of general medical comorbidity in physical functioning in both HIV-infected and HIV-negative patients. This suggests the importance of effectively treating comorbid conditions in persons with HIV, in order to reduce the overall impact of disease on physical functioning. C1 Baltimore VA Med Ctr, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. Yale Univ, Sch Med, New Haven, CT USA. W Haven VA Med Ctr, New Haven, CT USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. Greater Los Angeles VA Healthcare Syst Los Angele, Los Angeles, CA USA. Rutgers State Univ, Sch Social Work, New Brunswick, NJ 08903 USA. Rutgers State Univ, Inst Hlth Hlth Care Policy & Aging Res, New Brunswick, NJ 08903 USA. RP Oursler, KK (reprint author), Baltimore VA Med Ctr, BT 111,10 N Greene St, Baltimore, MD 21201 USA. EM Oursler@umbi.umd.edu OI Goulet, Joseph/0000-0002-0842-804X FU AHRQ HHS [418-HS016097]; NCRR NIH HHS [M01 RR016500]; NIA NIH HHS [5 P60 AG12583-09, K23 AG00826]; NIAAA NIH HHS [3U01 AA 13566]; NIMH NIH HHS [2R01-MH058984] NR 41 TC 38 Z9 38 U1 1 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1087-2914 J9 AIDS PATIENT CARE ST JI Aids Patient Care STDS PD NOV PY 2006 VL 20 IS 11 BP 782 EP 791 DI 10.1089/apc.2006.20.782 PG 10 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 114FJ UT WOS:000242651800006 PM 17134352 ER PT J AU Salem, RO Laposata, M Rajendram, R Cluette-Brown, JE Preedy, VR AF Salem, Raneem O. Laposata, Michael Rajendram, Rajkumar Cluette-Brown, Joanne E. Preedy, Victor R. TI The total body mass of fatty acid ethyl esters in skeletal muscles following ethanol exposure greatly exceeds that found in the liver and the heart SO ALCOHOL AND ALCOHOLISM LA English DT Article ID ADIPOSE-TISSUE; PROTEIN-SYNTHESIS; DIFFERENTIAL MOBILIZATION; POSTMORTEM MARKERS; RAT; MYOPATHY; APOPTOSIS; ALCOHOL; METABOLITES; ORGANS AB Aims: Skeletal muscle appears to be susceptible to chronic and acute excess alcohol intake, giving rise to alcoholic myopathy, a common disease among alcoholics. Fatty acid ethyl esters (FAEE), non-oxidative metabolites of ethanol, have been shown to be toxic to cells in vitro and in vivo. We hypothesized that accumulation of FAEE in skeletal muscle could contribute to the development of alcoholic myopathy. Methods: Male wistar rats were treated either with 75 mmol ethanol/kg body weight or saline, in the fed state or starved for 1 or 2 days before administration. Rats were thus divided into the following groups: fed-saline (n = 8); fed-ethanol (n = 8); starved 1 day, saline (n = 8); starved 1 day, ethanol (n = 9); starved 2 days, saline (n = 7); and starved 2 days, ethanol (n = 8). At the end of the incubation, skeletal muscles (abdominal and gastrocnemius), liver, and heart were isolated and processed for FAEE isolation and analysis by gas chromatography-mass spectrometry (GC-MS). Results: Total mass of FAEE in the muscles was much greater than that found in the liver and the heart. In general, the animals that were fasted for 1 day and received ethanol had the highest FAEE levels among the three groups of animals. The major ethyl ester species in all cases were ethyl 16:0, ethyl 18:0, ethyl 18:1 n-9, and ethyl 18:2 n-6. Ethyl 20:4 n-6 and ethyl 22:6 n-3 were also present, except in the fasted 1-day group, where ethyl 22:6 disappeared, though it reappeared in the fasted 2-day group. Conclusion: These findings demonstrate that skeletal muscles contain high levels of FAEE that are synthesized in the body after ethanol exposure. The concentration of FAEE in skeletal muscle in this study was very similar to FAEE concentration in the liver. This differs from previous studies suggesting a low concentration of skeletal muscle FAEE with ethanol exposure. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Div Lab Med, Dept Pathol, Boston, MA 02114 USA. Kings Coll London, Nutrit Sci Res Div, London SE1 9NU, England. RP Laposata, M (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Gray 235, Boston, MA 02114 USA. EM mlaposata@partners.org NR 38 TC 7 Z9 7 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0735-0414 J9 ALCOHOL ALCOHOLISM JI Alcohol Alcohol. PD NOV-DEC PY 2006 VL 41 IS 6 BP 598 EP 603 DI 10.1093/alcalc/agl069 PG 6 WC Substance Abuse SC Substance Abuse GA 104KY UT WOS:000241958500004 PM 16980711 ER PT J AU Beresford, TP Arciniegas, DB Alfers, J Clapp, L Martin, B Liu, YPDDF Shen, DG Davatzikos, C AF Beresford, Thomas P. Arciniegas, David B. Alfers, Julie Clapp, Lori Martin, Brandon Liu, Yiping Du Dengfeng Shen, Dinggang Davatzikos, Christos TI Hippocampus volume loss due to chronic heavy drinking SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE hippocampus; alcohol drinking; volume loss; MRI scan ID STRUCTURED CLINICAL INTERVIEW; ALCOHOL DEPENDENCE; ELASTIC REGISTRATION; SEX-DIFFERENCES; BRAIN; RELIABILITY; DISORDERS; DEFICITS; GENDER; HAMMER AB Objective: No clear consensus exists regarding the effect of sustained, heavy drinking on hippocampal volume. Our prior work hypothesized significantly lowered total hippocampus volumes in heavy chronically drinking alcohol-dependent (AD) subjects compared with light-drinking nondependent control subjects matched for age and gender. Method: Using a series of applicable exclusion criteria culled from previous published studies, we measured hippocampal volumes from MRI scan data acquired on a 3T scanner and subjected those data to automated volume analysis blind to the drinking history. Results: Comparison with AD test (n=8) and non-AD control (n=8) subjects found significant lessening in total (p=0.020) and left (p=0.010) hippocampal volumes with a near-significant difference on the right (p=0.051). Linear regression demonstrated that neither total brain volume nor intracranial volume affected the hippocampus measures. Conclusions: These data support the view that heavy drinking exerts a unique and selectively injurious effect on the hippocampus. Further study in larger samples must verify this in a search for possible mechanisms of injury. C1 Univ Colorado, Sch Med, Mental Hlth Serv, Dept Vet Affairs Med Ctr, Denver, CO USA. Univ Colorado, Sch Med, Dept Psychiat, Denver, CO 80262 USA. Univ Colorado, Sch Med, Dept Neurol, Denver, CO USA. Univ Colorado, Sch Med, Dept Radiol, Denver, CO USA. Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA. RP Beresford, TP (reprint author), Denver VA Med Ctr, 116,1055 Clermont St, Denver, CO 80220 USA. EM thomas.beresford@uchsc.edu RI Arciniegas, David/A-3792-2009 FU NIAAA NIH HHS [R21 AA 14010] NR 25 TC 70 Z9 71 U1 1 U2 8 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD NOV PY 2006 VL 30 IS 11 BP 1866 EP 1870 DI 10.1111/j.1530-0277.2006.00223.x PG 5 WC Substance Abuse SC Substance Abuse GA 098HA UT WOS:000241510400007 PM 17067350 ER PT J AU Bressler, B Sands, BE AF Bressler, B. Sands, B. E. TI Review article: medical therapy for fistulizing Crohn's disease SO ALIMENTARY PHARMACOLOGY & THERAPEUTICS LA English DT Review ID INFLAMMATORY-BOWEL-DISEASE; PERIANAL FISTULAS; LONG-TERM; METRONIDAZOLE THERAPY; ENDOSCOPIC ULTRASOUND; SERIOUS INFECTIONS; CONTROLLED-TRIAL; CYCLOSPORINE-A; INFLIXIMAB; 6-MERCAPTOPURINE AB Background Fistulae will develop in approximately one-third of patients with Crohn's disease. With an expected spontaneous healing rate of only 10%, fistulizing Crohn's disease requires a comprehensive strategy with a medical and possible surgical approach. Aim To summarize the current literature evaluating various medical options for treating patients with fistulizing Crohn's disease. Methods A literature review was conducted using PubMed (search terms: Crohn's disease and fistula) and manual search of references among the identified studies and relevant review papers to identify papers that present data on medical treatment of fistulizing Crohn's disease. Results The first line of medical therapy remains antibiotics (metronidazole and ciprofloxacin). Mercaptopurine and azathioprine are medications that are effective in treating fistulizing Crohn's disease. The current gold standard of medical treatment to induce and maintain remission for fistulizing Crohn's disease is infliximab. Used as induction therapy, infliximab produced a 62% clinical response, and a complete closure rate of 46%. A maintenance therapy trial demonstrated at 54 weeks, 46% of patients receiving infliximab continued to respond to treatment, compared with 23% in the placebo group (P = 0.001). Conclusions Further research to find new therapies and to improve our existing medical treatment of fistulizing Crohn's disease is required. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Crohns & Colitis Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Univ British Columbia, St Pauls Hosp, Div Gastroenterol, Vancouver, BC V5Z 1M9, Canada. RP Sands, BE (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, Crohns & Colitis Ctr, 165 Cambridge St,9th Floor, Boston, MA 02114 USA. EM bsands@partners.org NR 66 TC 20 Z9 20 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0269-2813 J9 ALIMENT PHARM THERAP JI Aliment. Pharmacol. Ther. PD NOV 1 PY 2006 VL 24 IS 9 BP 1283 EP 1293 DI 10.1111/j.1365-2036.2006.03126.x PG 11 WC Gastroenterology & Hepatology; Pharmacology & Pharmacy SC Gastroenterology & Hepatology; Pharmacology & Pharmacy GA 095XS UT WOS:000241342200002 PM 17059510 ER PT J AU Orakzai, SH Orakzai, RH Nasir, K Santos, RD Edmundowicz, D Budoff, MJ Blumenthal, RS AF Orakzai, Sarwar H. Orakzai, Raza H. Nasir, Khurram Santos, Raul D. Edmundowicz, Daniel Budoff, Matthew J. Blumenthal, Roger S. TI Subdinical coronary atherosclerosis: Racial profiling is necessary! SO AMERICAN HEART JOURNAL LA English DT Article ID BEAM COMPUTED-TOMOGRAPHY; ACUTE MYOCARDIAL-INFARCTION; ARTERY RISK DEVELOPMENT; ETHNIC-DIFFERENCES; AFRICAN-AMERICAN; YOUNG-ADULTS; CARDIOVASCULAR-DISEASE; PROGNOSTIC VALUE; NATURAL-HISTORY; WHITE SUBJECTS AB Objectives We aim to review the studies comparing coronary calcification across different ethnic groups. Background There is still uncertainty regarding ethnic differences in the prevalence, progression, and risk of coronary artery disease. Clues to possible racial differences in rates of coronary heart disease (CHD) may be found by identifying subclinical disease. Coronary artery calcification (CAC) can be used to predict risk of CHID in both symptomatic and asymptomatic subjects. Methods Online databases were searched for studies assessing racial differences in CAC. Results Most of the published studies have shown that racial differences exist in the prevalence and severity of CAC. Whites have a higher prevalence of CAC as compared to African Americans and other ethnic groups even after adjustment for risk factors. These differences in CAC are even more pronounced in men and in the elderly. Data regarding the distribution of CAC in ethnic groups outside the United States are limited. Emerging evidence indicates that while several ethnic groups outside the United States tend to have a greater prevalence of CHD risk factors, their prevalence of CAC is lower, as compared with Americans. Thus, the data obtained in the United States may not be able to be fully extrapolated to populations outside the United States for assessment of CHD risk. Conclusions The presence and extent of CAC varies among different racial groups within and outside the United States. The relationship between calcification and the incidence of CHD in these ethnic groups needs further exploration. Thus, it is important to develop ethnic specific CAC nomograms to more accurately determine the underlying CHD risk associated with CAC in these individuals. It will also be imperative to obtain outcome data and relate it to baseline levels of CAC to help us put in perspective the significance of racial differences in CAC and how they impact on cardiac risk prediction. C1 Univ Pittsburgh, Dept Med, Med Ctr, Pittsburgh, PA USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Univ Sao Paulo, Lipid Clin Heart Inst, Incor, Med Sch Hosp, Sao Paulo, Brazil. Univ Calif Los Angeles, Div Cardiol, Los Angeles Biomed Res Inst, Torrance, CA USA. Johns Hopkins Univ, Sch Med, Ciccarone Prevent Cardiol Ctr, Baltimore, MD USA. RP Blumenthal, RS (reprint author), Johns Hopkins Univ Hosp, Ciccarone Prevent Cardiol Ctr, Blalock 524 C Cardiol,600 N Wolfe St, Baltimore, MD 21287 USA. EM rblument@jhmi.edu RI Santos, Raul/A-1170-2010 OI Santos, Raul/0000-0002-9860-6582 NR 59 TC 33 Z9 33 U1 0 U2 0 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 NOV PY 2006 VL 152 IS 5 BP 819 EP 827 DI 10.1016/j.ahj.2006.08.008 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 101MV UT WOS:000241745800005 PM 17070140 ER PT J AU Amin, AA Jones, AMH Nugent, K Rumsfeld, JS Spertus, JA AF Amin, Alpesh A. Jones, Angela M. H. Nugent, Karen Rumsfeld, John S. Spertus, John A. TI The prevalence of unrecognized depression in patients with acute coronary syndrome SO AMERICAN HEART JOURNAL LA English DT Article ID QUALITY-OF-LIFE; MYOCARDIAL-INFARCTION; HEALTH QUESTIONNAIRE; MORTALITY RISK; PRIMARY-CARE; SYMPTOMS; VALIDITY; DISORDERS; SEVERITY; DISEASE AB Background Depression in patients with acute coronary syndrome (ACS) is common and independently prognostic of a higher mortality and worse health status. Despite great attention to its prevalence and prognostic import, little is known about how often hospitalized patients with ACS who have significant depressive symptoms are recognized while receiving routine cardiovascular care. Methods We performed a cross-sectional study of 1181 consecutive patients with confirmed ACS. Detailed reviews of hospital records were performed for the documentation that depressive symptoms were recognized. Multivariable regression analysis was used to identify factors associated with unrecognized depressive symptoms. Results The prevalence of moderate/severe depressive symptoms was 17.6%. Only 24.5% had documentation that their depressive symptoms were recognized. In multivariable regression analysis, characteristics associated with unrecognized depressive symptoms were race (minorities vs whites; odds ratio [OR]=6.73, 95% confidence interval [CI] 2.62-19.33), ejection fraction (EF < 0.40 vs EF >= 0.40; OR=3.45, 95% CI 1.06-11.23), and education level (no college vs some college; OR=2.77, 95% Cl 1.38-5.69). Conclusions Despite its prognostic importance and prevalence, moderate to severe depressive symptoms are poorly recognized in hospitalized patients with ACS. Better interventions are warranted to increase the recognition and improve the management of depressive symptoms in patients with ACS. C1 St Lukes Hosp, Mid Amer Heart Inst, Kansas City, MO 64111 USA. Univ Missouri, Kansas City, MO 64110 USA. Univ Colorado, Denver, CO 80202 USA. Denver VA Med Ctr, Denver, CO USA. Univ Missouri, Truman Med Ctr, Kansas City, MO 64108 USA. RP Amin, AA (reprint author), 4401 Wornall Rd, Kansas City, MO 64111 USA. EM aamin@saint-lukes.org FU AHRQ HHS [R-01 HS11282-01] NR 30 TC 34 Z9 34 U1 2 U2 6 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 NOV PY 2006 VL 152 IS 5 BP 928 EP 934 DI 10.1016/j.ahj.2006.05.006 PG 13 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 101MV UT WOS:000241745800026 PM 17070162 ER PT J AU Ruo, B Bertenthal, D Sen, S Bittner, V Ireland, CC Hlatky, MA AF Ruo, Bernice Bertenthal, Daniel Sen, Saunak Bittner, Vera Ireland, Christine C. Hlatky, Mark A. TI Self-rated health among women with coronary disease: Depression is as important as recent cardiovascular events SO AMERICAN HEART JOURNAL LA English DT Article ID INFLAMMATORY RISK MARKERS; DWELLING OLDER ADULTS; ARTERY-DISEASE; HEART-DISEASE; MYOCARDIAL-INFARCTION; CARDIAC MORTALITY; CES-D; SYMPTOMS; COMMUNITY; ASSOCIATION AB Background Prior studies have shown an association between depression and self-rated health among patients with coronary disease. However, the magnitude of the effect of depression on self-rated health compared with that of major clinical events is unknown. Our main objective was to clarify the association between depression and self-rated health using longitudinal data. Methods We performed a prospective cohort study of 2675 postmenopausal women with coronary disease. The primary predictor variable was a 4-state categorical depression variable based on the Burnam depression screen assessed at sequential visits. The outcome variable was self-rated overall health (excellent, very good, or good vs fair or poor). Results After adjustment for age, comorbidities, prior self-rated health, and interim events, women with depression at both current and prior annual visits had a > 5-fold increased odds of fair/poor self-rated health (odds ratio [OR] 5.1, 95% Cl 3.8-6.8). New depression was associated with a > 2-fold increased odds of fair/poor self-rated health (OR 2.6, 95% Cl 2.0-3.4). Having a history of depression at the preceding annual visit but not at the current visit was associated with a slight increased odds of fair/poor self-rated health (OR 1.3, 95% Cl 1.0-1.7). The magnitude of the impact of persistent or new depression was comparable to that of recent angina, myocardial infarction, angioplasty, heart failure, or bypass surgery. Conclusions Women with persistent or new depression are more likely to report fair/poor self-rated health. The magnitude of the impact of persistent or new depression is comparable to that of major cardiac events. C1 Northwestern Univ, Div Gen Internal Med, Feinberg Sch Med, Dept Internal Med, Chicago, IL 60611 USA. San Francisco Vet Affairs Med Ctr, Hlth Serv Res Enhancement Award Program, San Francisco, CA USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Univ Alabama, Div Cardiovasc Dis, Birmingham, AL 35294 USA. Stanford Univ, Sch Med, Stanford, CA 94305 USA. RP Ruo, B (reprint author), Northwestern Univ, Div Gen Internal Med, Feinberg Sch Med, Dept Internal Med, 676 N St Clair St,Suite 200, Chicago, IL 60611 USA. EM bruo@nmff.org OI Bittner, Vera/0000-0001-9456-850X NR 37 TC 5 Z9 5 U1 1 U2 1 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 NOV PY 2006 VL 152 IS 5 AR 921.e1 DI 10.1016/j.ahj.2006.01.012 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 101MV UT WOS:000241745800024 ER PT J AU Tricoci, P Peterson, ED Mulgund, J Newby, LK Saucedo, JF Kleiman, NS Bhatt, DL Berger, PB Cannon, CP Cohen, DJ Hochman, JS Ohman, EM Gibler, WB Harrington, RA Smith, SC Roe, MT AF Tricoci, Pierluigi Peterson, Eric D. Mulgund, Jyotsna Newby, L. Kristin Saucedo, Jorge F. Kleiman, Neil S. Bhatt, Deepak L. Berger, Peter B. Cannon, Christopher P. Cohen, David J. Hochman, Judith S. Ohman, E. Magnus Gibler, W. Brian Harrington, Robert A. Smith, Sidney C., Jr. Roe, Matthew T. CA CRUSADE Investigators TI Temporal trends in the use of early cardiac catheterization in patients with non-ST-segment elevation acute coronary syndromes (results from CRUSADE) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID EARLY INVASIVE MANAGEMENT; PRACTICE GUIDELINES COMMITTEE; ASSOCIATION TASK-FORCE; UNSTABLE ANGINA; MYOCARDIAL-INFARCTION; AMERICAN-COLLEGE; ARTERY DISEASE; TROPONIN-T; STRATEGIES; BENEFIT AB We evaluated temporal trends in the use of early (< 48 hours) catheterization in patients with non-ST-segment elevation acute coronary syndromes with respect to baseline risk features since publication of the American College of Cardiology/American Heart Association guidelines, which include a class IA recommendation for an early invasive strategy for high-risk patients with non-ST-segment elevation acute coronary syndromes. Overall, we found that early catheterization use increased from 53% to 61% during the 3 years after the guidelines were released, but the increased use of early catheterization was highest (11%) in the group that was at lowest risk of predicted mortality, and it was lowest (6%) in the group at highest risk of predicted mortality who would potentially receive the most benefit from an aggressive treatment approach. In conclusion, despite the overall increase in the use of early catheterization, the gap between the use of an early invasive strategy in the highest and lowest risk patients remains large and tends to increase over time. (c) 2006 Elsevier Inc. All rights reserved. C1 Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27706 USA. Univ N Carolina, Sch Med, Chapel Hill, NC 27515 USA. Univ Oklahoma, Ctr Hlth Sci, Norman, OK 73019 USA. Methodist DeBakey Heart cTR, Houston, TX USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Univ Cincinnati, Sch Med, Dept Emergency Med, Cincinnati, OH 45221 USA. Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NYU, Sch Med, New York, NY USA. RP Tricoci, P (reprint author), Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27706 USA. OI Hochman, Judith/0000-0002-5889-5981 NR 17 TC 34 Z9 35 U1 0 U2 1 PU EXCERPTA MEDICA INC PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD NOV 1 PY 2006 VL 98 IS 9 BP 1172 EP 1176 DI 10.1016/j.amjcard.2006.05.047 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 104TL UT WOS:000241982200010 PM 17056321 ER PT J AU Sheth, TN Rieber, J Mooyaart, EAQ Pena, A Abbara, S Cury, RC Brady, T Hoffmann, U AF Sheth, Tej N. Rieber, Johannes Mooyaart, Eline A. Q. Pena, Antonio Abbara, Suhny Cury, Ricardo C. Brady, Tom Hoffmann, Udo TI Usefulness of coronary computed tomographic angiography to assess suitability for revascularization in patients with significant coronary artery disease and angina pectoris SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID LESIONS; INTERVENTION; ACCURACY AB Coronary computed tomographic angiography (CTA) accurately excludes the presence of coronary stenoses in selected patient populations. However, it remains unclear whether coronary CTA has the potential to replace invasive coronary angiography as a tool to assess a patient's suitability for revascularization as determined by the characterization of lesion morphology in patients with significant coronary artery disease. Coronary CTA (64-slice computed tomography) was performed before invasive coronary angiography in 29 patients. We evaluated the accuracy of CTA for the detection of complex lesion morphology, including the presence of severe calcium, total occlusions, and ostial or bifurcation location, and compared the results with those of invasive angiography. On CTA, 10 of 69 lesions (15%) were not evaluable for any feature of complex lesion morphology. Of the evaluable lesions, CTA detected >= 1 feature of complexity in 58% of lesions, corresponding to a sensitivity of 88% (23 of 26) and a specificity of 83% (24 of 29). For those single features, the sensitivity of CTA was 100% for the presence of severe calcium, 93% for total occlusions, and 60% and 80% for the detection of ostial and bifurcation lesions, respectively. The specificity was high for total occlusions (97%), ostial lesions (97%), and bifurcations (100%). It was moderate (85%) for severe calcium. Severe calcium precluded the evaluation of other features of complex lesion morphology in 6 lesions (11%). In conclusion, invasive selective coronary angiography remains the cornerstone to assess a patient's suitability for revascularization given the high proportion of unevaluable segments and segments with severe calcium that precluded adequate revascularization planning on CTA. (c) 2006 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Cardiac MR PETCT Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Hoffmann, U (reprint author), Massachusetts Gen Hosp, Cardiac MR PETCT Program, Boston, MA 02114 USA. EM uhoffmann@partners.org NR 10 TC 11 Z9 11 U1 0 U2 0 PU EXCERPTA MEDICA INC PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD NOV 1 PY 2006 VL 98 IS 9 BP 1198 EP 1201 DI 10.1016/j.amjcard.2006.05.053 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 104TL UT WOS:000241982200016 PM 17056327 ER PT J AU Wang, SA Galili, N Cerny, J Sechman, E Chen, SS Loew, J Liu, Q Fadare, O Hasserjian, R Jones, D Qawi, H Woda, B Raza, A AF Wang, Sa A. Galili, Naomi Cerny, Jan Sechman, Eric Chen, Su Sin Loew, Jerome Liu, Qin Fadare, Oluwole Hasserjian, Robert Jones, Dan Qawi, Huma Woda, Bruce Raza, Azra TI Chronic myelomonocytic leukemia evolving from preexisting myelodysplasia shares many features with de Novo disease SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE chronic myelomonocytic leukemia; myelodysplastic syndrome; evolution; overall survival ID COLONY-STIMULATING FACTOR; MARROW MONOCYTIC NODULES; ACUTE MYELOID-LEUKEMIA; TYROSINE KINASE JAK2; MYELOPROLIFERATIVE-DISORDERS; IN-VITRO; PROGNOSTIC-SIGNIFICANCE; RETROSPECTIVE ANALYSIS; POLYCYTHEMIA-VERA; RISK-ASSESSMENT AB The majority of chronic myelomonocytic leukemia (CMML) cases arise de novo; cases evolving from preexisting myelodysplasia (MDS) or myeloproliferative diseases have not been well-studied. We conducted the present study to determine the clinicopathologic features and to study possible underlying molecular and cytogenetic mechanisms involved in this evolution. Between April 1995 and November 2005, we identified 120 CMML cases, of which 20 (16.7%) had a previous diagnosis of MDS. Of the 20 patients with MDS, 6 had relative monocytosis at diagnosis. At the time of MDS to CMML evolution, mutations in JAK2 (V617F), FLT3 (ITD), K-ras-2, or N-ras were not acquired, and only 1 (6%) of 17 evaluable cases showed cytogenetic progression. The median time to evolution from MDS to CMML was 29 months, and the median survival following CMML development was 13 months. Three cases (17%) transformed to acute myeloid leukemia. These findings indicate that in some cases of otherwise typical MDS, the progenitor cells may have some capacity for monocytic proliferation at diagnosis and manifest rapid disease progression once a monocytic proliferation supervenes. C1 Univ Massachusetts, Med Ctr, Dept Pathol, Worcester, MA 01605 USA. Univ Massachusetts, Med Ctr, Dept Med, Worcester, MA 01605 USA. Univ Massachusetts, Med Ctr, Dept Canc Biol, Worcester, MA 01605 USA. Univ Texas, MD Anderson Canc Ctr, Dept Hematopathol, Houston, TX 77030 USA. Rush Univ, Med Ctr, Dept Pathol, Chicago, IL 60612 USA. Wilford Hall USAF Med Ctr, Dept Pathol, San Antonio, TX 78236 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA USA. RP Wang, SA (reprint author), Univ Massachusetts, Med Ctr, Dept Pathol, 1 Innovat Dr, Worcester, MA 01605 USA. RI Jones, Daniel/I-7399-2015 NR 39 TC 18 Z9 20 U1 0 U2 1 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 NOV PY 2006 VL 126 IS 5 BP 789 EP 797 DI 10.1309/FU04P779U310R3EE PG 9 WC Pathology SC Pathology GA 097BA UT WOS:000241420000016 PM 17050076 ER PT J AU Rahemtullah, A Reichard, KK Preffer, FI Harris, NL Hasserjian, RP AF Rahemtullah, Aliyah Reichard, Kaaren K. Preffer, Frederic I. Harris, Nancy L. Hasserjian, Robert P. TI A double-positive CD4+CD8+T-cell population is commonly found in nodular lymphocyte predominant Hodgkin lymphoma SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE hematopathology; nodular lymphocyte predominant; Hodgkin lymphoma; flow cytometry; T cell; double positive; CD4; CD8; fine-needle aspiration; cytology ID FINE-NEEDLE-ASPIRATION; FLOW-CYTOMETRY; PROGRESSIVE TRANSFORMATION; GERMINAL-CENTERS; LYMPHOPROLIFERATIVE DISORDERS; T-CELLS; DISEASE; DIAGNOSIS; CLASSIFICATION; PATTERNS AB Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a distinct subtype of Hodgkin lymphoma in which T-cell subsets have not been studied specifically. We reviewed 24 cases of NLPHL and compared flow cytometric results with those of 13 progressively transformed germinal centers (PTGC) cases, 78 nonspecific reactive hyperplasia (RH) cases, and 31 classical Hodgkin lymphoma (CHL) cases. A double-positive (CD4+CD8+) T-cell population was present in 58% of NLPHL cases, constituting 10% to 38% of T cells. The cells were CD3+, CD5+, CD2+, CD7+, CD1a- and terminal deoxynucleotidyl transferase-. Similar CD4+CD8+ T cells were identified in 38% of PTGC cases (P = .31), 4% of RH specimens (P < .00001), and 6% of CHL specimens (P < .0001). The presence of a CD4+CD8+ T-cell population in NLPHL may reflect an activated or reactive T-cell subset and should not lead to a misdiagnosis of T-cell lymphoma. This population may be a clue to the diagnosis of NLPHL, particularly in cases with limited tissue. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ New Mexico, Albuquerque, NM 87131 USA. RP Rahemtullah, A (reprint author), Massachusetts Gen Hosp, Dept Pathol, WRN 219,55 Fruit St, Boston, MA 02114 USA. NR 30 TC 34 Z9 35 U1 0 U2 1 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 NOV PY 2006 VL 126 IS 5 BP 805 EP 814 DI 10.1309/Y8KD32QGRYFN1XQX PG 10 WC Pathology SC Pathology GA 097BA UT WOS:000241420000018 PM 17050078 ER PT J AU Neuman, MI Radeos, MS Yang, A Gordon, JA Camargo, CA AF Neuman, Mark I. Radeos, Michael S. Yang, Anthony Gordon, James A. Camargo, Carlos A., Jr. TI Does parental report of insurance status agree with hospital administrative data for children presenting to the ED? SO AMERICAN JOURNAL OF EMERGENCY MEDICINE LA English DT Article; Proceedings Paper CT Annual Meeting of the Society-for-Academic-Emergency-Medicine CY MAY 29-JUN 01, 2003 CL BOSTON, MA SP Soc Acad Emergency Med C1 Childrens Hosp, Div Emergency Med, Boston, MA 02115 USA. Lincoln Med Ctr, Dept Emergency Med, Bronx, NY 10451 USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Neuman, MI (reprint author), Childrens Hosp, Div Emergency Med, 300 Longwood Ave, Boston, MA 02115 USA. EM mark.neuman@childrens.harvard.edu FU NICHD NIH HHS [T32 HD40128-01] NR 7 TC 1 Z9 1 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 0735-6757 J9 AM J EMERG MED JI Am. J. Emerg. Med. PD NOV PY 2006 VL 24 IS 7 BP 890 EP 892 DI 10.1016/j.ajem.2006.03.019 PG 3 WC Emergency Medicine SC Emergency Medicine GA 109DD UT WOS:000242287200029 PM 17098122 ER PT J AU Lau, M Le, A El-Serag, HB AF Lau, Melvin Le, Anne El-Serag, Hashem B. TI Noncardia gastric adenocarcinoma remains an important and deadly cancer in the United States: Secular trends in incidence and survival SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID CARCINOMA; STOMACH; STATISTICS; PATTERNS; CARDIA; USA AB BACKGROUND: Noncardia gastric adenocarcinoma is not frequently mentioned in the United States. However, it is unclear if the previously reported decline in noncardia gastric adenocarcinoma has continued, and if detection and management has affected overall survival outside the setting of clinical trials. METHODS: We used the Surveillance, Epidemiology, and End Results registry (SEER) to identify all cases of noncardia gastric adenocarcinoma diagnosed between 1973 and 2002. The yearly age-adjusted incidence rates and the relative survival rates were calculated. Cox proportional hazards (PH) models were used to examine temporal trends from 1983 to 2003. RESULTS: Between 1973 and 2002, there were 24,103 cases of noncardia gastric adenocarcinoma. The age-adjusted yearly incidence rate declined by 23% between 1973 and 2002 from 4.3 to 3.3 per 100,000 person-years. However, the incidence of localized noncardia gastric adenocarcinoma (invasive neoplasm confined to the organ of origin) remained without change between 0.9 and 1.0 per 100,000 person-years, and increased with age, especially in the 85+ yr age group (a 47% increase between 1973 and 2002). The incidence rates in men were double those in women, and 1.6-fold and 2.6-fold higher in blacks and other races (mostly Asians), respectively, compared with whites. Patients with radiation and chemotherapy after gastrectomy had a 22% better mortality risk compared with those treated with gastrectomy alone. The Cox PH analysis shows no significant change in mortality risk related to year of diagnosis between 1983 and 2002, both in unadjusted as well as adjusted analyses. However, there were significant independent regional and racial variations in survival. Asians had a 17% lower mortality risk compared with whites. CONCLUSIONS: Despite the overall decline in noncardia gastric adenocarcinoma, the incidence of local stage disease has remained stable in most ages and even increased in old ages. Unfortunately, there has been no significant improvement in survival during the past 20 yr. Moreover, there remain considerable regional as well as racial variations in mortality. C1 Baylor Coll Med, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Dept Surg, Houston, TX 77030 USA. Houston Dept Vet Affairs Med Ctr, Gastroenterol Sect, Houston, TX USA. Houston Dept Vet Affairs Med Ctr, Sect Hlth Serv Res, Houston, TX USA. RP El-Serag, HB (reprint author), Houston Vet Affairs Med Ctr, 152,2002 Holcombe Blvd, Houston, TX 77030 USA. NR 20 TC 45 Z9 47 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 NOV PY 2006 VL 101 IS 11 BP 2485 EP 2492 DI 10.1111/j.1572-0241.2006.00778.x PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 101GH UT WOS:000241728300008 PM 17029617 ER PT J AU Khalid, A Nodit, L Zahid, M Bauer, K Brody, D Finkelstein, SD McGrath, KM AF Khalid, Asif Nodit, Laurentia Zahid, Maliha Bauer, Kathy Brody, Debra Finkelstein, Sydney D. McGrath, Kevin M. TI Endoscopic ultrasound fine needle aspirate DNA analysis to differentiate malignant and benign pancreatic masses SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID AUTOIMMUNE-RELATED PANCREATITIS; TUMOR-SUPPRESSOR GENE; K-RAS; INTRAEPITHELIAL NEOPLASIA; SCLEROSING PANCREATITIS; CLINICAL UTILITY; DIAGNOSIS; ADENOCARCINOMA; P53; MUTATIONS AB OBJECTIVES: Accurate diagnosis of malignant and benign pancreatic masses can be challenging, potentially delaying treatment for cancer and subjecting patients with benign disease to unnecessary surgery. Endoscopic ultrasound fine needle aspirate (EUS-FNA) of pancreatic masses remains inconclusive in a subset of patients. The role of EUS-FNA molecular analysis in this context is studied. METHODS: Patients with benign pancreatic masses (6 cases, 4 autoimmune pancreatitis, 2 focal chronic pancreatitis) and malignant pancreatic masses (15) with inconclusive cytology (5 cases) and positive cytology (10 controls) were selected. All cases had definitive pathology. Representative cells were microdissected from each EUS-FNA sample and subjected to PCR for analysis of 16 microsatellite allele loss markers situated at 1p, 3p, 5q, 9p, 9q, 10q, 17p, 17q, 21q, and 22q. Loss of heterozygosity analysis used fluorescent capillary electrophoresis for quantitative determination of allelic imbalance. k-ras-2 point mutation analysis was also performed. Mean fractional mutation rate (FMR) was calculated and compared for each group. RESULTS: All malignant cases carried multiple mutations (FMR 0.50), regardless of positive cytology (FMR 0.52) or suspicious cytology (FMR 0.47) (p = NS). Five of the 6 benign cases carried no mutations whereas 1 case of autoimmune pancreatitis and coexisting PanIN lesions exhibited a k-ras mutation (FMR 0.01). The mean FMR for the malignant and benign samples was significantly different (p < 0.0001). CONCLUSIONS: Broad panel microsatellite loss and k-ras point mutation analysis can be reliably performed on EUS-FNA samples from pancreatic masses and improves the diagnostic accuracy. Furthermore, it accurately differentiates between malignant and benign pancreatic masses. C1 Univ Pittsburgh, Med Ctr, Dept Med,VA Pittsburgh Hlth Care Syst, Div Gastroenterol Hepatol & Nutr,PUH, Pittsburgh, PA 15213 USA. VA Pittsburgh Hlth Care, Pittsburgh, PA USA. Univ Pittsburgh, Dept Pathol, Pittsburgh, PA USA. RedPath Integrated Pathol Inc, Pittsburgh, PA USA. RP Khalid, A (reprint author), Univ Pittsburgh, Med Ctr, Dept Med,VA Pittsburgh Hlth Care Syst, Div Gastroenterol Hepatol & Nutr,PUH, M2,C Wing,200 Lothrop St, Pittsburgh, PA 15213 USA. NR 41 TC 60 Z9 63 U1 0 U2 1 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 NOV PY 2006 VL 101 IS 11 BP 2493 EP 2500 DI 10.1111/j.1572-0241.2006.00740.x PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 101GH UT WOS:000241728300009 PM 17029619 ER PT J AU Mutsuddi, M Morris, DW Waggoner, SG Daly, MJ Scolnick, EM Sklar, P AF Mutsuddi, Mousumi Morris, Derek W. Waggoner, Skye G. Daly, Mark J. Scolnick, Edward M. Sklar, Pamela TI Analysis of high-resolution HapMap of DTNBP1 (dysbindin) suggests no consistency between reported common variant associations and schizophrenia SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID FAMILY-BASED ASSOCIATION; RISK HAPLOTYPE; GENE DTNBP1; 6P22.3 GENE; EXPRESSION; IDENTIFICATION; LOCUS; GENOME; BRAIN; IRISH AB DTNBP1 was first identified as a putative schizophrenia-susceptibility gene in Irish pedigrees, with a report of association to common genetic variation. Several replication studies have reported confirmation of an association to DTNBP1 in independent European samples; however, reported risk alleles and haplotypes appear to differ between studies, and comparison among studies has been confounded because different marker sets were employed by each group. To facilitate evaluation of existing evidence of association and further work, we supplemented the extensive genotype data, available through the International HapMap Project (HapMap), about DTNBP1 by specifically typing all associated single-nucleotide polymorphisms reported in each of the studies of the Centre d'Etude du Polymorphisme Humain (CEPH)-derived HapMap sample (CEU). Using this high-density reference map, we compared the putative disease-associated haplotype from each study and found that the association studies are inconsistent with regard to the identity of the disease-associated haplotype at DTNBP1. Specifically, all five "replication" studies define a positively associated haplotype that is different from the association originally reported. We further demonstrate that, in all six studies, the European-derived populations studied have haplotype patterns and frequencies that are consistent with HapMap CEU samples (and each other). Thus, it is unlikely that population differences are creating the inconsistency of the association studies. Evidence of association is, at present, equivocal and unsatisfactory. The new dense map of the region may be valuable in more-comprehensive follow-up studies. C1 Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. Harvard Univ, Cambridge, MA 02138 USA. MIT, Psychiat Dis Initiat, Cambridge, MA 02139 USA. MIT, Med & Populat Genet Program, Broad Inst, Cambridge, MA 02139 USA. St James Hosp, Trinity Coll, Inst Mol Med, Neuropsychiat Genet Grp, Dublin 8, Ireland. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Ctr Human Genet Res, Boston, MA 02115 USA. RP Sklar, P (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, 185 Cambridge St,Room 6242, Boston, MA 02114 USA. EM sklar@chgr.mgh.harvard.edu OI Morris, Derek/0000-0002-3413-570X NR 26 TC 70 Z9 73 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2006 VL 79 IS 5 BP 903 EP 909 DI 10.1086/508942 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 100KJ UT WOS:000241667400011 PM 17033966 ER PT J AU Darouiche, RO Goetz, L Kaldis, T Cerra-Stewart, C AlSharif, A Priebe, M AF Darouiche, Rabih O. Goetz, Lance Kaldis, Teresa Cerra-Stewart, Colleen AlSharif, Atef Priebe, Michael TI Impact of StatLock securing device on symptomatic catheter-related urinary tract infection: A prospective, randomized, multicenter clinical trial SO AMERICAN JOURNAL OF INFECTION CONTROL LA English DT Article; Proceedings Paper CT 15th Annual Meeting of the Society-for-Healthcare-Epidemiology-of-America CY APR 09-12, 2005 CL Los Angeles, CA SP Soc Healthcare Epidemiol Amer ID CENTRAL VENOUS CATHETERS; SPINAL-CORD INJURY; BLOOD-STREAM INFECTION; DOUBLE-BLIND; TRIMETHOPRIM-SULFAMETHOXAZOLE; BACTERIAL INTERFERENCE; HOSPITALIZED-PATIENTS; PILOT TRIAL; MEATAL CARE; PREVENTION AB Background: The objective of this study was to assess the impact of using the StatLock securing device on symptomatic catheter-related urinary tract infection (UTI). Methods: In this prospective, randomized, multicenter clinical trial, adult patients with spinal cord injury or dysfunction because of multiple sclerosis were randomized to have their indwelling bladder catheters secured in place by using the StatLock device (experimental group) versus preexisting methods (control group that included tape, Velcro strap, CathSecure, or none). Patients were monitored for the development of symptomatic UTI within the subsequent period of 8 weeks. Results: Of a total of 127 enrolled patients, 118 (60 in the experimental group and 58 in the control group) were evaluable. The 2 groups of evaluable patients were comparable in terms of clinical characteristics and risk factors for infection. Symptomatic UTI was diagnosed in 8 of 60 (13.3%) patients in the experimental group versus 14 of 58 (24.1%) patients in the control group (P = .16; RR = 0.55, 95% confidence interval: 0.25-1.22). Conclusion: Although the trial size precluded the demonstration of statistically significant differences, the finding of a 45% reduction in the rate of symptomatic UTI in patients who received the StatLock securing device is clinically relevant and prompts further investigations. C1 Baylor Coll Med, Ctr Prostheses Infect, Houston, TX 77030 USA. Michael E Debakey Vet Affairs Med Ctr, Houston, TX USA. Vet Affairs N Texas Healthcare Syst, Dallas, TX USA. Univ Texas, SW Med Ctr, Dallas, TX 75230 USA. Inst Rehabil & Res, Houston, TX USA. Hines Vet Affairs Med Ctr, Hines, IL USA. RP Darouiche, RO (reprint author), Baylor Coll Med, Ctr Prostheses Infect, 1333 Moursund Ave,Suite A221, Houston, TX 77030 USA. EM rdarouiche@aol.com NR 36 TC 22 Z9 22 U1 1 U2 3 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0196-6553 J9 AM J INFECT CONTROL JI Am. J. Infect. Control PD NOV PY 2006 VL 34 IS 9 BP 555 EP 560 DI 10.1016/j.ajic.2006.03.010 PG 6 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 105MX UT WOS:000242035400003 PM 17097449 ER PT J AU Bryson, CL Ross, HJ Boyko, EJ Young, BA AF Bryson, Chris L. Ross, Heather J. Boyko, Edward J. Young, Bessie A. TI Racial and ethnic variations in albuminuria in the US Third National Health and Nutrition Examination Survey (NHANES III) population: Associations with diabetes and level of CKD SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE race; ethnicity; microalbuminuria; macroalbuminuria; proteinuria; diabetes; chronic kidney disease; cohort study ID BLOOD-PRESSURE; YOUNG-ADULTS; MICROALBUMINURIA AB Background: Racial and ethnic differences in prevalence of albuminuria in a nationally representative population with and without diabetes were assessed. Methods: We analyzed cross-sectional data collected for the 20,050 participants of the Third National Health and Nutrition Examination Survey (NHANES 111) to determine factors that contributed to racial/ethnic differences in microalbuminuria and macroalbuminuria prevalence. Results: For the 15,522 NHANES III participants for whom relevant data were available, racial/ethnic minorities tended to be younger, be less well educated, have lower income, and be less likely to have insurance than non-Hispanic whites, findings that were similar for those with and without diabetes. After adjusting for baseline covariates and medication use, racial and ethnic minorities with and without diabetes had greater odds of alburninuria compared with whites without diabetes (blacks with diabetes, adjusted odds ratio [aOR], 2.77; 95% confidence interval [CI], 1.46 to 2.72), Mexican Americans with diabetes (aOR, 2.43; 95% Cl, 1.07 to 2.11), and those of other ethnicity with diabetes (aOR, 2.93; 95% Cl, 1.28 to 6.75). Of those without diabetes, blacks had 2.18-fold (95% Cl, 1.44 to 3.30) and Mexican Americans had 1.81-fold (95% Cl, 1.08 to 3.02) greater odds of microalbuminuria or macroalbuminuria than whites after adjustment for potential confounding factors. Stratifying by estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73 m(2) (<1.00 mUs) showed similar results for racial/ethnic minorities and those with diabetes, whereas results were significant only for blacks with and without diabetes for those with an eGFR of 60 mL/min/1.73 m(2) or greater. Level of metabolic control (hemoglobin A(1c) level), systolic blood pressure, income, diuretic use, and hypertensive treatment status remained independent factors associated with alburninuria. Conclusion: Racial and ethnic minorities have greater odds of albuminuria than whites with and without diabetes, which persists primarily for those with an eGFR less than 60 mL/min/1.73m(2). C1 Epidemiol Res & Informat Ctr, VA Puget Sound Hlth Care Syst, Seattle, WA 98101 USA. NW Ctr Excellence,Hlth Serv Res & Dev, VA Puget Sound Hlth Care Syst, Seattle, WA 98101 USA. Univ Washington, Dept Med, Div Gen Internal Med, Seattle, WA USA. NW Kidney Ctr, Seattle, WA USA. RP Young, BA (reprint author), Epidemiol Res & Informat Ctr, VA Puget Sound Hlth Care Syst, 1100 Olive Way,Ste 1400, Seattle, WA 98101 USA. EM youngb@u.washington.edu NR 20 TC 63 Z9 63 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 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD NOV PY 2006 VL 48 IS 5 BP 720 EP 726 DI 10.1053/j.ajkd.2006.07.023 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 197FV UT WOS:000248540900004 PM 17059991 ER PT J AU Szabo, CA Lancaster, JL Lee, S Xiong, JH Cook, C Mayes, BN Fox, PT AF Szabo, C. A. Lancaster, J. L. Lee, S. Xiong, J. -H. Cook, C. Mayes, B. N. Fox, P. T. TI MR imaging volumetry of subcortical structures and cerebellar hemispheres in temporal lobe epilepsy SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID VOXEL-BASED MORPHOMETRY; QUANTITATIVE MRI; HIPPOCAMPAL ATROPHY; PARTIAL SEIZURES; THALAMUS; BRAIN; DURATION; AMYGDALA; ORIGIN; MATTER AB BACKGROUND AND PURPOSE: There is mounting evidence of extratemporal volume changes associated with medically refractory temporal lobe epilepsy (TLE). This MR imaging study aimed to characterize volume changes in subcortical structures and cerebellar hemispheres with respect to lateralization of the seizure focus, onset and duration of epilepsy, and frequency of generalized tonic-clonic seizures (GTCS). METHODS: Amygdalar, hippocampal, thalamic, caudate head, and cerebellar volume measurements were obtained in the preoperative MR images of 40 patients with TLE (20 right, 20 left), who underwent temporal lobe resection with good outcome, and in 20 right-handed control participants. All 3D MR images were spatially aligned and normalized before measurements were obtained. Standardized volumes and right-to-left volume ratios (VRs) were compared between control participants and right and left TLE groups. Multiple regression analyses were performed to study the effects of epilepsy onset and duration and GTCS frequency on ipsilateral-to-contra lateral VRs with respect to the resected seizure focus. RESULTS: Thalamic volumes were smaller bilaterally in patients with TLE. Hippocampal volumes were smaller ipsilateral to the seizure focus, but there was no significant volume loss involving the amygdala, caudate, or cerebellum. Hippocampal and annygdalar right-to-left VRs differed significantly between right and left TLE groups and controls, whereas thalamic right-to-left VRs differed only between the TLE groups. Thalamic ipsilateral-to-contralateral VRs were correlated positively with epilepsy onset and negatively with epilepsy duration. Caudate ipsilateral-to-contra lateral VRs were positively, whereas annygdalar and cerebellar VRs were negatively, correlated with GTCS frequency. CONCLUSIONS: Unilateral annygdalar and bilateral thalamic volume loss, in the absence of caudate head atrophy, is likely to reflect seizure-induced injury due to TLE. Correlations of VRs affecting the amygdala, caudate, and cerebellum with GTCS frequency may also reflect injury or a prediposition for secondary generalization. Potential effects of complex partial seizures, febrile seizures, or antiepileptic medications on subcortical structures need to be evaluated in future studies. C1 Univ Texas, Hlth Sci Ctr, Dept Med Neurol, S Texas Comprehens Epilepsy Ctr, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Res Imaging Ctr, San Antonio, TX 78229 USA. Audie L Murphy Mem Vet Adm Med Ctr, Res & Dev Serv, San Antonio, TX 78284 USA. Univ Iowa, Dept Radiol, Iowa City, IA 52242 USA. RP Szabo, CA (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med Neurol, S Texas Comprehens Epilepsy Ctr, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM Charles.Szabo@uhs-sa.com RI Lancaster, Jack/F-2994-2010; Fox, Peter/B-4725-2010 OI Fox, Peter/0000-0002-0465-2028 FU NIDA NIH HHS [P20 DA52176] NR 27 TC 33 Z9 35 U1 1 U2 9 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 NOV-DEC PY 2006 VL 27 IS 10 BP 2155 EP 2160 PG 6 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 109CE UT WOS:000242284700032 PM 17110687 ER PT J AU Huang, AJ Thom, DH Kanaya, AM Wassel-Fyr, CL Van Den Eeden, SK Ragins, AI Subak, LL Brown, JS AF Huang, A. J. Thom, D. H. Kanaya, A. M. Wassel-Fyr, C. L. Van Den Eeden, S. K. Ragins, A. I. Subak, L. L. Brown, J. S. TI Urinary incontinence and pelvic floor dysfunction in Asian-American women SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE urinary incontinence; anal incontinence; fecal incontinence; pelvic organ prolapse; pelvic floor dysfunction; Asian-American; Asian; race; ethnicity ID TAIWANESE WOMEN; PREVALENCE; IMPACT; POPULATION; SYMPTOMS; DISTRESS; SEEKING; HEALTH; AGE AB Objective: The objective of the study was to describe the prevalence, risk factors, and impact of urinary incontinence and other pelvic floor disorders among Asian-American women. Study design: This was a population-based cohort study of older women randomly selected from age and race strata. Results: Weekly urinary incontinence was reported by 65 of 345 Asian women (18%), with stress and urge incontinence being approximately equally common. In multivariate analysis, higher body mass index (greater than 25 kg/m(2)) was associated with both stress incontinence (odds ratio 4.90, 95% confidence interval 1.76 to 13.68) and urge incontinence (odds ratio 2.49, 95% confidence interval 1.01 to 6.16) in Asians. Hysterectomy was a significant risk factor for stress incontinence (odds ratio 2.79, 95% confidence interval 1.03 to 7.54). Only 34% of Asian women with weekly urinary incontinence reported ever having sought treatment. Pelvic floor exercises were the most common form of treatment, being used by 29% of Asian women with weekly incontinence. Asians were-less likely then white women to report anal incontinence (21% versus 29%, P = .007), although this difference became nonsignificant after adjusting for differences in risk factors. Conclusion: Asian women share some risk factors for stress and urge urinary incontinence with white women. Urinary incontinence is associated with anal incontinence among Asian women. (c) 2006 Mosby, Inc. All rights reserved. C1 San Francisco Vet Affairs Med Ctr, Div Gen Med, San Francisco, CA 94121 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Kaiser Permanente, Div Res, Oakland, CA USA. RP Huang, AJ (reprint author), San Francisco Vet Affairs Med Ctr, Div Gen Med, 4150 Clement St,VAMC 111A1, San Francisco, CA 94121 USA. EM ajhuan@yahoo.com FU NIDDK NIH HHS [P50 DK064538, P50 DK044538, R01 DK053335, R01-DK53335] NR 23 TC 16 Z9 17 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD NOV PY 2006 VL 195 IS 5 BP 1331 EP 1337 DI 10.1016/j.ajog.2006.03.052 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 105MZ UT WOS:000242035700022 PM 16643821 ER PT J AU Bruce, BB Newman, NJ Biousse, V AF Bruce, Beau B. Newman, Nancy J. Biousse, Valerie TI Ophthalmoparesis in idiopathic intracranial hypertension SO AMERICAN JOURNAL OF OPHTHALMOLOGY LA English DT Article ID CHIARI-I MALFORMATION AB PURPOSE: To report unusual ocular motility disturbances in the setting of idiopathic intracranial hypertension (IIH). DESIGN: Interventional case series. METHODS: Two cases with IIH and unusual ophthalmopareses are reported. RESULTS: Two patients with confirmed IIH presented with headache, diplopia, and papilledema. The first patient had bilateral sixth nerve palsies and a partial right third nerve palsy, which resolved rapidly after a cerebro spinal fluid (CSF) shunting procedure; the second patient had alternating skew deviation and upbeat nystagmus. Both cases had normal brain magnetic resonance imaging (MRI) and magnetic resonance venography (MRV) and normal CSF contents, ruling out a secondary cause of intracranial hypertension. CONCLUSIONS: These exceptional vertical and horizontal ophthalmopareses in the setting of IIH may be related directly to very elevated CSF pressures and may be secondary to altered CSF flow in the posterior fossa. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02115 USA. Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA. Emory Univ, Sch Med, Dept Ophthalmol, Atlanta, GA 30322 USA. Emory Univ, Sch Med, Dept Neurol Surg, Atlanta, GA 30322 USA. RP Biousse, V (reprint author), Emory Eye Ctr, Neuroophthalmol Unit, 1365-B Clifton Rd,NE, Atlanta, GA 30322 USA. EM vbiouss@emory.edu OI Bruce, Beau/0000-0003-3003-2962 FU NEI NIH HHS [P30-EY06360] NR 4 TC 14 Z9 14 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9394 J9 AM J OPHTHALMOL JI Am. J. Ophthalmol. PD NOV PY 2006 VL 142 IS 5 BP 878 EP 880 DI 10.1016/j.ajo.2006.06.007 PG 3 WC Ophthalmology SC Ophthalmology GA 107AK UT WOS:000242142900034 PM 17056379 ER PT J AU Perell, KL Manzano, MLP Weaver, R Fiuzat, M Voss-McCarthy, M Opava-Rutter, D Castle, SC AF Perell, Karen L. Manzano, Maria Lyn P. Weaver, Robert Fiuzat, Mona Voss-McCarthy, Michelle Opava-Rutter, Dorene Castle, Steven C. TI Outcomes of a consult fall prevention screening clinic SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Article DE geriatrics; fall prevention; aged; patient satisfaction; pharmacology ID RANDOMIZED CONTROLLED-TRIAL; COMMUNITY; INTERVENTION; HOME; RISK; GO AB Objective: To report patient satisfaction and quality outcomes from a standardized, multicenter fall prevention screening clinic. Design: Referrals were made to the fall prevention screening clinic, which was staffed by a physician, pharmacist, therapist, nurse, and the site coordinator. The fall prevention screening clinic staff utilized a team-meeting format with clearly delineated management options to determine the appropriate interventions based on various screening examinations. Results: Primary care providers acknowledged pharmacy recommendations and > 80% of the recommendations were followed. There was a reduction in reported falls (initial visit = 297 falls, follow-up visit = 141 falls, P = 0.0002) and in the number of recurrent fallers. There was a small (average difference = 1.8 secs) but significant (P = 0.025) decrease in the 8-foot Up-and-Go time, representing a functional improvement in walking speed. There was no significant change in the Fall Efficacy Scale, however. At least > 80% of the patients reported that they were completely satisfied with their care. Conclusions: Patients who attended the fall prevention screening clinic demonstrated improved confidence during activities of daily living and reduced falls. They reported high satisfaction with the clinic format. C1 Calif State Univ Fullerton, Dept Kinesiol, Fullerton, CA 92834 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. San Francisco VA Med Ctr, San Francisco, CA USA. RP Perell, KL (reprint author), Calif State Univ Fullerton, Dept Kinesiol, Fullerton, CA 92834 USA. NR 18 TC 6 Z9 6 U1 6 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0894-9115 J9 AM J PHYS MED REHAB JI Am. J. Phys. Med. Rehabil. PD NOV PY 2006 VL 85 IS 11 BP 882 EP 888 DI 10.1097/01.phm.0000233209.49518.46 PG 7 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 098OL UT WOS:000241532400004 PM 17079960 ER PT J AU Fujii, N Jessen, N Goodyear, LJ AF Fujii, Nobuharu Jessen, Niels Goodyear, Laurie J. TI AMP-activated protein kinase and the regulation of glucose transport SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Review DE skeletal muscle; heart; LKB1 drug target; exercise ID RAT SKELETAL-MUSCLE; ACETYL-COA CARBOXYLASE; FATTY-ACID OXIDATION; GAMMA-SUBUNIT ISOFORMS; NITRIC-OXIDE SYNTHASE; GLUT4 TRANSLOCATION; CONTRACTILE ACTIVITY; MALONYL-COA; MAP KINASE; YEAST SNF1 AB The AMP-activated protein kinase (AMPK) is an energy-sensing enzyme that is activated by acute increases in the cellular [AMP]/[ATP] ratio. In skeletal and/or cardiac muscle, AMPK activity is increased by stimuli such as exercise, hypoxia, ischemia, and osmotic stress. There are many lines of evidence that increasing AMPK activity in skeletal muscle results in increased rates of glucose transport. Although similar to the effects of insulin to increase glucose transport in muscle, it is clear that the underlying mechanisms for AMPK-mediated glucose transport involve proximal signals that are distinct from that of insulin. Here, we discuss the evidence for AMPK regulation of glucose transport in skeletal and cardiac muscle and describe research investigating putative signaling mechanisms mediating this effect. We also discuss evidence that AMPK may play a role in enhancing muscle and whole body insulin sensitivity for glucose transport under conditions such as exercise, as well as the use of the AMPK activator AICAR to reverse insulin-resistant conditions. The identification of AMPK as a novel glucose transport mediator in skeletal muscle is providing important insights for the treatment and prevention of type 2 diabetes. 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 02115 USA. Univ Aarhus, Med Res Lab, DK-8000 Aarhus C, Denmark. Univ Aarhus, Dept Clin Pharmacol, DK-8000 Aarhus C, Denmark. RP Goodyear, LJ (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. EM Laurie.Goodyear@joslin.harvard.edu RI Jessen, Niels/E-1731-2011; Fujii, Nobuharu/J-2724-2014; OI Fujii, Nobuharu/0000-0002-0974-3033; Jessen, Niels/0000-0001-5613-7274 FU NIAMS NIH HHS [AR-42238, R01-AR-45670] NR 132 TC 125 Z9 133 U1 0 U2 12 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 NOV PY 2006 VL 291 IS 5 BP E867 EP E877 DI 10.1152/ajpendo.00207.2006 PG 11 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 092OC UT WOS:000241106200001 PM 16822958 ER PT J AU Sakamoto, K Arnolds, DE Fujii, N Kramer, HF Hirshman, MF Goodyear, LJ AF Sakamoto, Kei Arnolds, David E. Fujii, Nobuharu Kramer, Henning F. Hirshman, Michael F. Goodyear, Laurie J. TI Role of Akt2 in contraction-stimulated cell signaling and glucose uptake in skeletal muscle SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE exercise; glycogen; glycogen synthase kinase-3 ID GLYCOGEN-SYNTHASE KINASE-3; MICE LACKING; INSULIN; EXERCISE; PROTEIN; PHOSPHORYLATION; TRANSPORT; GROWTH; ACTIVATION; RESISTANCE AB The serine/threonine kinase Akt/PKB plays diverse roles in cells, and genetic studies have indicated distinct roles for the three Akt isoforms expressed in mammalian cells and tissues. Akt2 is a key signaling intermediate for insulin-stimulated glucose uptake and glycogen synthesis in skeletal muscle. Akt2 has also been shown to be activated by exercise and muscle contraction in both rodents and humans. In this study, we used Akt2 knockout mice to explore the role of Akt2 in exercise-stimulated glucose uptake and glycogen synthesis as well as intracellular signaling pathways that regulate glycogen metabolism in skeletal muscle. We found that Akt2 deficiency does not affect basal or exercise-stimulated glucose uptake or intracellular glycogen content in the soleus muscle. In addition, lack of Akt2 did not result in alterations in basal Akt Thr(308) or basal and contraction-stimulated glycogen synthase kinase-3 beta (GSK-3 beta) Ser(9) phosphorylation, glycogen synthase phosphorylation, or glycogen synthase activity. In contrast, in situ contraction failed to elicit normal increases in Akt T-loop Thr(308) phosphorylation and GSK-3 alpha Ser(21) phosphorylation in tibialis anterior muscles from Akt2-deficient animals. Our data establish a key role for Akt2 in the regulation of GSK-3 alpha Ser(21) phosphorylation with contraction and add genetic evidence to support the separation of the intracellular pathways regulated by insulin and exercise that converge on glucose uptake and glycogen synthesis in skeletal muscle. C1 Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept 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 RI Fujii, Nobuharu/J-2724-2014 OI Fujii, Nobuharu/0000-0002-0974-3033 FU NIAMS NIH HHS [AR-42238]; NIDDK NIH HHS [DK-68626] NR 48 TC 29 Z9 31 U1 0 U2 2 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 NOV PY 2006 VL 291 IS 5 BP E1031 EP E1037 DI 10.1152/ajpendo.00204.2006 PG 7 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 092OC UT WOS:000241106200021 PM 16803855 ER PT J AU Khan, WI Motomura, Y Wang, H El-Sharkawy, RT Verdu, EF Verma-Gandhu, M Rollins, BJ Collins, SM AF Khan, W. I. Motomura, Y. Wang, H. El-Sharkawy, R. T. Verdu, E. F. Verma-Gandhu, M. Rollins, B. J. Collins, S. M. TI Critical role of MCP-1 in the pathogenesis of experimental colitis in the context of immune and enterochromaffin cells SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE monocyte chemottractant protein-1; dinitrobenzenesulfonic acid; CD3-positive cells; 5-hydroxytryptamine; serotonin ID INFLAMMATORY-BOWEL-DISEASE; MONOCYTE CHEMOATTRACTANT PROTEIN-1; DEXTRAN SODIUM-SULFATE; ULCERATIVE-COLITIS; CROHNS-DISEASE; CHEMOKINE RECEPTORS; CHEMOTACTIC PROTEIN-1; CYTOKINE RESPONSES; T-CELLS; MICE AB Mucosal changes in inflammatory bowel disease (IBD) are characterized by ulcerative lesions accompanied by a prominent infiltrate of inflammatory cells including lymphocytes, macrophages, and neutrophils and alterations in 5-hydroxytryptamine (5-HT)-producing enterochromaffin (EC) cells. Mechanisms involved in recruiting and activating these cells are thought to involve a complex interplay of inflammatory mediators. Studies in clinical and experimental IBD have shown the upregulation of various chemokines including monocyte chemottractant protein (MCP)-1 in mucosal tissues. However, precise information on the roles of this chemokine or the mechanisms by which it takes part in the pathogenesis of IBD are not clear. In this study, we investigated the role of MCP-1 in the development of hapten-induced experimental colitis in mice deficient in MCP-1. Our results showed a significant reduction in the severity of colitis both macroscopically and histologically along with a decrease in mortality in MCP-1-deficient mice compared with wild-type control mice. This was correlated with a downregulation of myeloperoxidase activity, IL-1 beta, IL-12p40, and IFN-gamma production, and infiltration of CD3(+) T cells and macrophages in the colonic mucosa. In addition, we observed significantly lower numbers of 5-HT-expressing EC cells in the colon of MCP-1-deficient mice compared with those in wild-type mice after dinitrobenzenesulfonic acid. These results provide evidence for a critical role of MCP-1 in the development of colonic inflammation in this model in the context of immune and enteric endocrine cells. C1 McMaster Univ, Hlth Sci Ctr, Dept Med, Intestinal Dis Res Program, Hamilton, ON L8N 3Z5, Canada. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. RP Khan, WI (reprint author), McMaster Univ, Hlth Sci Ctr, Dept Med, Intestinal Dis Res Program, 1200 Main St W,Rm 3N5D, Hamilton, ON L8N 3Z5, Canada. EM khanwal@mcmaster.ca RI El-Sharkawy, Rami/C-3473-2008 NR 50 TC 60 Z9 63 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD NOV PY 2006 VL 291 IS 5 BP G803 EP G811 DI 10.1152/ajpgi.00069.2006 PG 9 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 092NE UT WOS:000241103100006 PM 16728728 ER PT J AU Mukherjee, R Mingoia, JT Bruce, JA Austin, JS Stroud, RE Escobar, GP McClister, DM Allen, CM Alfonso-Jaume, MA Fini, ME Lovett, DH Spinale, FG AF Mukherjee, Rupak Mingoia, Joseph T. Bruce, James A. Austin, Jeffrey S. Stroud, Robert E. Escobar, G. Patricia McClister, David M., Jr. Allen, Claire M. Alfonso-Jaume, Maria A. Fini, M. Elizabeth Lovett, David H. Spinale, Francis G. TI Selective spatiotemporal induction of matrix metalloproteinase-2 and matrix metalloproteinase-9 transcription after myocardial infarction SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE structure; remodeling; matrix metalloproteinases ID LEFT-VENTRICULAR ENLARGEMENT; PREVENTS CARDIAC RUPTURE; TARGETED DELETION; HEART-FAILURE; TISSUE INHIBITOR; RAT MYOCARDIUM; MICE; EXPRESSION; MMP-2; CELLS AB Myocardial remodeling after myocardial infarction (MI) is associated with increased levels of the matrix metalloproteinases (MMPs). Levels of two MMP species, MMP-2 and MMP-9, are increased after MI, and transgenic deletion of these MMPs attenuates post-MI left ventricular (LV) remodeling. This study characterized the spatiotemporal patterns of gene promoter induction for MMP-2 and MMP-9 after MI. MI was induced in transgenic mice in which the MMP-2 or MMP-9 promoter sequence was fused to the beta-galactosidase reporter, and reporter level was assayed up to 28 days after MI. Myocardial localization with respect to cellular sources of MMP-2 and MMP-9 promoter induction was examined. After MI, LV diameter increased by 70% (P < 0.05), consistent with LV remodeling. beta-Galactosidase staining in MMP-2 reporter mice was increased by 1 day after MI and increased further to 64 +/- 6% of LV epicardial area by 7 days after MI (P < 0.05). MMP-2 promoter activation occurred in fibroblasts and myofibroblasts in the MI region. In MMP-9 reporter mice, promoter induction was detected after 3 days and peaked at 7 days after MI (53 +/- 6%, P < 0.05) and was colocalized with inflammatory cells at the peri-infarct region. Although MMP-2 promoter activation was similarly distributed in the MI and border regions, activation of the MMP-9 promoter was highest at the border between the MI and remote regions. These unique findings visually demonstrated that activation of the MMP-2 and MMP-9 gene promoters occurs in a distinct spatial relation with reference to the MI region and changes in a characteristic time-dependent manner after MI. C1 Med Univ S Carolina, Div Cardiovasc Surg, Charleston, SC 29425 USA. Ralph H Johnson Vet Adm Med Ctr, Charleston, SC USA. Univ Miami, Miller Sch Med, Bascom Palmer Eye Inst, McKnight Vis Res Ctr, Miami, FL 33152 USA. Univ Calif San Francisco, Vet Affairs Med Ctr, Dept Med, San Francisco, CA 94143 USA. RP Mukherjee, R (reprint author), Med Univ S Carolina, Div Cardiovasc Surg, Strom thurmond Res Bldg,770 MUSC Complex,Ste 625, Charleston, SC 29425 USA. EM mukherr@musc.edu FU NEI NIH HHS [EY-14801, EY-12651]; NHLBI NIH HHS [HL-66029, HL-45024, P01-HL-48788, P01-HL-68738, HL-97012]; NIDDK NIH HHS [DK-29776] NR 45 TC 51 Z9 52 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD NOV PY 2006 VL 291 IS 5 BP H2216 EP H2228 DI 10.1152/ajpheart.01343.2005 PG 13 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 092NB UT WOS:000241102700027 PM 16766634 ER PT J AU Rush, AJ Trivedi, MH Wisniewski, SR Nierenberg, AA Stewart, JW Warden, D Niederehe, G Thase, ME Lavori, PW Lebowitz, BD McGrath, PJ Rosenbaum, JF Sackeim, HA Kupfer, DJ Luther, J Fava, M AF Rush, A. John Trivedi, Madhukar H. Wisniewski, Stephen R. Nierenberg, Andrew A. Stewart, Jonathan W. Warden, Diane Niederehe, George Thase, Michael E. Lavori, Philip W. Lebowitz, Barry D. McGrath, Patrick J. Rosenbaum, Jerrold F. Sackeim, Harold A. Kupfer, David J. Luther, James Fava, Maurizio TI Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: A STAR*D report SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID SEQUENCED TREATMENT ALTERNATIVES; TREATMENT-RESISTANT DEPRESSION; MEDICATION ALGORITHM PROJECT; ILLNESS RATING-SCALE; REPORT QIDS-SR; QUICK INVENTORY; PSYCHOMETRIC EVALUATION; CLINICAL GUIDELINES; MAJOR DEPRESSION; DISORDERS AB Objective: This report describes the participants and compares the acute and longer-term treatment outcomes associated with each of four successive steps in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial. Method: A broadly representative adult outpatient sample with nonpsychotic major depressive disorder received one (N = 3,671) to four (N = 123) successive acute treatment steps. Those not achieving remission with or unable to tolerate a treatment step were encouraged to move to the next step. Those with an acceptable benefit, preferably symptom remission, from any particular step could enter a 12-month naturalistic follow-up phase. A score of = 5 on the Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR16) (equivalent to = 7 on the 17-item Hamilton Rating Scale for Depression [HRSD17]) defined remission; a QIDS-SR16 total score of = 11 (HRSD17 >= 14) defined relapse. Results: The QIDS-SR16 remission rates were 36.8%, 30.6%, 13.7%, and 13.0% for the first, second, third, and fourth acute treatment steps, respectively. The overall cumulative remission rate was 67%. Overall, those who required more treatment steps had higher relapse rates during the naturalistic follow-up phase. In addition, lower relapse rates were found among participants who were in remission at follow-up entry than for those who were not after the first three treatment steps. Conclusions: When more treatment steps are required, lower acute remission rates (especially in the third and fourth treatment steps) and higher relapse rates during the follow-up phase are to be expected. Studies to identify the best multistep treatment sequences for individual patients and the development of more broadly effective treatments are needed. C1 Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX 75390 USA. Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15260 USA. Massachusetts Gen Hosp, Cln Psychopharmacol Unit, Boston, MA 02114 USA. New York State Psychiat Inst & Hosp, New York, NY 10032 USA. Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY 10027 USA. NIMH, Bethesda, MD 20892 USA. Stanford Univ, VA Cooperat Studies Program, Stanford, CA 94305 USA. Univ Calif San Diego, Sam & Rose Stein Inst Res Aging, La Jolla, CA 92093 USA. RP Rush, AJ (reprint author), Univ Texas, SW Med Ctr, Dept Psychiat, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM john.rush@utsouthwestern.edu RI McGrath, Patrick/I-6410-2013; OI McGrath, Patrick/0000-0001-7217-7321; Wisniewski, Stephen/0000-0002-3877-9860; Rush, Augustus/0000-0003-2004-2382 FU NIMH NIH HHS [N01MH90003] NR 59 TC 1335 Z9 1375 U1 16 U2 88 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 NOV PY 2006 VL 163 IS 11 BP 1905 EP 1917 DI 10.1176/appi.ajp.163.11.1905 PG 13 WC Psychiatry SC Psychiatry GA 100LF UT WOS:000241669900014 PM 17074942 ER PT J AU Hoffmann, U Pena, AJ Moselewski, F Ferencik, M Abbara, S Cury, RC Chae, CU Nagurney, JT AF Hoffmann, Udo Pena, Antonio J. Moselewski, Fabian Ferencik, Maros Abbara, Suhny Cury, Ricardo C. Chae, Claudia U. Nagurney, John T. TI MDCT in early triage of patients with acute chest pain SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE acute coronary syndrome; cardiac imaging; CT coronary arteriography; coronary artery disease; emergency radiology; MDCT; patient management ID SPIRAL COMPUTED-TOMOGRAPHY; ACUTE CORONARY SYNDROMES; ACUTE MYOCARDIAL-INFARCTION; PRACTICE GUIDELINES COMMITTEE; ASSOCIATION TASK-FORCE; ACUTE CARDIAC ISCHEMIA; AMERICAN-COLLEGE; ARTERY-DISEASE; INTRAVASCULAR ULTRASOUND; ATHEROSCLEROTIC PLAQUE AB OBJECTIVE. Current risk stratification of patients with acute chest pain but normal initial cardiac enzymes and nondiagnostic ECG is inefficient. We sought to determine whether contrast-enhanced MDCT-based detection of stenosis is feasible and improves early and accurate triage of patients with acute chest pain. SUBJECTS AND METHODS. We studied 40 patients (53% men; mean age, 57 +/- 13 years) with chest pain who were awaiting hospital admission to rule out an acute coronary syndrome (ACS) despite the absence of diagnostic ECG changes and normal cardiac enzymes on emergency department presentation. Patients underwent contrast-enhanced MDCT before hospital admission. Afterward, patients received standard clinical care. All physicians involved in the patients' care were blinded to the results of MDCT. An expert panel established the presence or absence of ACS based on American Heart Association (AHA) guidelines. The MDCT images were evaluated for the presence of significant coronary artery stenosis (diameter reduction > 50%) and were used to make a triage decision. RESULTS. All five patients (12.5%) with ACS (one with non-ST elevation myocardial infarction, four with unstable angina pectoris) had at least one significant coronary stenosis on MDCT (sensitivity, 100% [95% Cl, 49-100%)]. ACS was ruled out in 35 patients (87.5%). Significant coronary stenosis was excluded in 26 of the 35 patients without ACS by MDCT (specificity, 74% [CI, 75-88%]), potentially saving 70% of unnecessary hospital admissions. CONCLUSION. MDCT-based detection of significant coronary stenoses has tremendous potential to decrease the number of unnecessary hospital admissions, without reducing appropriate admission rates, in patients with chest pain who have nondiagnostic ECG results and normal cardiac enzymes. These results are likely to further improve with advances in MDCT technology. C1 Massachusetts Gen Hosp, Dept Radiol, MR CT PET Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Hoffmann, U (reprint author), Massachusetts Gen Hosp, Dept Radiol, MR CT PET Program, 100 CPZ 400, Boston, MA 02114 USA. EM uhoffman@partners.org NR 40 TC 45 Z9 45 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 NOV PY 2006 VL 187 IS 5 BP 1240 EP 1247 DI 10.2214/AJR.05.2240 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 098HE UT WOS:000241510800019 PM 17056911 ER PT J AU Chan, DPN Abujudeh, HH Cushing, GL Novelline, RA AF Chan, David P. N. Abujudeh, Hani H. Cushing, George L., Jr. Novelline, Robert A. TI CT cystography with multiplanar reformation for suspected bladder rupture: Experience in 234 cases SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article; Proceedings Paper CT 91st Scientific Assembly and Annual Meeting of the Radiological-Society-of-North-America CY NOV 27-DEC 02, 2005 CL Chicago, IL SP Radiol Soc N Amer DE bladder trauma; CT cystography; multiplanar reformation ID COMPUTERIZED-TOMOGRAPHY; HELICAL CT; TRAUMA AB OBJECTIVE. CT cystography has replaced conventional cystography in the evaluation of patients with suspected bladder rupture in most trauma centers. We performed this retrospective review to determine the accuracy of CT cystography and the role of multiplanar reformation in the diagnosis of bladder injury. MATERIALS AND METHODS. The patient cohort was composed of trauma patients with clinically or CT-suspected bladder ruptures who were evaluated with CT cystography using two different MDCT scanners at our level I trauma center. The patients were identified through Folio, a radiology research tool software system. The CT cystography results were compared with the findings at surgery, clinical follow-up, or both. RESULTS. Between January 1, 2000, and December 31, 2004, 234 patients were examined in our level I trauma center with CT cystography. From the total of 234 examinations, 216 (92.3%) were interpreted as negative and 18 examinations (7.7%) were interpreted as positive. On the 18 positive examinations, 11 were extraperitoneal bladder rupture, five were intraperitoneal bladder rupture, and two were combined intraperitoneal and extraperitoneal bladder rupture. Surgical bladder exploration and repair were performed in nine of the 18 cases. Seven (77.8%) of the nine cases had operative findings consistent with the CT cystogram findings. The overall sensitivity and specificity of CT cystography in diagnosing bladder rupture were each 100%. For extraperitoneal bladder rupture, the sensitivity and specificity were 92.8% and 100%, respectively. For intraperitoneal rupture, the sensitivity and specificity were 100% and 99%, respectively. CONCLUSION. CT cystography is accurate for diagnosing bladder rupture. Sagittal and coronal multiplanar reformations may be helpful in identifying most sites of bladder rupture. C1 Prince Wales Hosp, Dept Diagnost Radiol & Organ Imaging, Shatin, Hong Kong, Peoples R China. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Chan, DPN (reprint author), Prince Wales Hosp, Dept Diagnost Radiol & Organ Imaging, Shatin, Hong Kong, Peoples R China. EM chanponin@gmail.com NR 11 TC 32 Z9 34 U1 1 U2 1 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 NOV PY 2006 VL 187 IS 5 BP 1296 EP 1302 DI 10.2214/AJR.05.0971 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 098HE UT WOS:000241510800027 PM 17056919 ER PT J AU Shetty, SK Maher, MM Hahn, PF Halpern, EF Aquino, SL AF Shetty, Sanjay K. Maher, Michael M. Hahn, Peter F. Halpern, Elkan F. Aquino, Suzanne L. TI Significance of incidental thyroid lesions detected on CT: Correlation among CT, sonography, and pathology SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE CT; head and neck imaging; sonography; thyroid gland ID FINE-NEEDLE-ASPIRATION; MICROFOLLICULAR NODULE; COMPUTED-TOMOGRAPHY; SUSPECTED CANCER; ULTRASOUND; BIOPSY; ULTRASONOGRAPHY; MALIGNANCY; DIAGNOSIS; CRITERIA AB OBJECTIVE. The purpose of our study was to determine the prevalence of malignancy in incidental abnormalities of the thyroid gland detected on CT and to determine the relative accuracy of characterizing these abnormalities on CT as compared with sonography and pathology. MATERIALS AND METHODS. We searched our department's computerized clinical database for all thoracic and cervical CT scans in which a new abnormality was incidentally identified in the thyroid gland from 1998-2001. Two hundred thirty patients with abnormal findings in the gland on CT subsequently underwent thyroid sonography, and 118 of the 230 patients underwent a diagnostic biopsy or resection. CT and sonographic images were directly reviewed to identify imaging features of each thyroid abnormality, including the location, size, appearance, and presence or absence of calcifications. Associations were evaluated using Fisher's exact test of significance and the Student's t test. The overall rate of malignant and potentially malignant lesions among these incidental abnormalities of the thyroid gland was calculated. RESULTS. CT findings matched the sonographic characterization in 122 patients (53.0%), correctly identified the dominant nodule but missed multinodularity in 69 (30.0%) patients, and underestimated the number of nodules in 24 (10.4%) patients. CT overestimated the number of nodules in 5 (2.2%) patients and was false-positive for lesions in 10 patients (4.3%). Ninety-one patients with a single or dominant nodule on CT had pathologic correlation: 7 nodules were malignant, 17 showed malignant potential, and 67 were benign. Of 27 patients with multinodular or enlarged thyroid glands on CT and histopathologic correlation, 2 lesions were malignant and 25 benign. The presence of punctate calcifications on CT significantly correlated to the presence of microcalcifications on sonography (p < 0.02). Benign nodules were significantly smaller (mean, 2.16 +/- 1.01 cm; range, 0.6-4.5 cm) than malignant and potentially malignant nodules (mean, 2.79 +/- 0.99 cm; range, 0.7-4.6 cm) (p = 0.01). Patients 35 years or younger who had a thyroid lesion on CT were more likely to have malignancy (P < 0.0 1). Overall, among incidentally detected lesions of the thyroid gland, there was at least a 3.9% rate of malignancy (95% CI: 1.8-7.3%) and 7.4% rate of malignant potential (95% Cl: 4.4-11.6%). CONCLUSION. There is at least an 11.3% prevalence of malignant or potentially malignant lesions among incidental thyroid abnormalities detected on CT. Patients 35 years or younger who have incidental abnormalities have a significantly greater rate of malignancy. No CT feature reliably distinguishes benign from malignant lesions in the thyroid gland. CT underestimates the number of nodules relative to sonography, which suggests that sonography is a useful adjunctive test after the incidental detection of a thyroid abnormality on CT. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Shetty, SK (reprint author), Beth Israel Deaconess Med Ctr, Dept Radiol, 330 Brookline Ave, Boston, MA 02215 USA. EM sshetty@bidmc.harvard.edu NR 19 TC 86 Z9 91 U1 0 U2 4 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 NOV PY 2006 VL 187 IS 5 BP 1349 EP 1356 DI 10.2214/AJR.05.0468 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 098HE UT WOS:000241510800036 PM 17056928 ER PT J AU Gilman, MD Fischman, AJ Krishnasetty, V Halpern, EF Aquino, SL AF Gilman, Matthew D. Fischman, Alan J. Krishnasetty, Vikram Halpern, Elkan F. Aquino, Suzanne L. TI Optimal CT breathing protocol for combined thoracic PET/CT SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE computer-assisted; image analysis; CT; image reconstruction; positron emission; PET/CT ID CELL LUNG-CANCER; POSITRON-EMISSION-TOMOGRAPHY; DUAL-MODALITY PET/CT; COMPUTED-TOMOGRAPHY; REGISTRATION AB OBJECTIVE. The objective of this study was to determine the optimal breathing protocol for combined PET/CT scans of the thorax. SUBJECTS AND METHODS. Eighty combined PET/CT scans were obtained in 64 patients (30 women, 34 men; mean age, 57 years; range, 19-86 years). The 80 PET/CT scans consisted of five group of patients (16 PET/CT scans per group) who underwent whole-body combined F-18-FDG PET/CT with different CT breathing protocols: expiration, mid suspended breath-hold, quiet breathing, small breath in, and regular breath in. The quality of alignment was analyzed at the diaphragm, aortic arch, heart, thoracic spine, and lung apices using a scale of ratings from I (very poor) to 5 (excellent). The Kruskal-Wallis test was used to compare alignment between breathing protocols for each anatomic reference point. RESULTS. Alignment of the PET and CT data sets was excellent with three breathing protocols: expiration, mid suspended breath-hold, and quiet breathing, with no statistical differences. Significant misalignment occurred at the diaphragm (p < 0.0001) and heart (p < 0.0001) with the small breath-in and regular breath-in techniques. CONCLUSION. Excellent image fusion of combined PET/CT data sets in the thorax, especially at the diaphragm and heart, can be achieved with expiration, mid suspended breathhold, or quiet breathing. Quiet breathing is recommended for optimal patient comfort during acquisition of attenuation-correction CT data sets. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. RP Aquino, SL (reprint author), Massachusetts Gen Hosp, Dept Radiol, FND 202,55 Fruit St, Boston, MA 02114 USA. EM saquino@partners.org NR 8 TC 32 Z9 33 U1 1 U2 1 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 NOV PY 2006 VL 187 IS 5 BP 1357 EP 1360 DI 10.2214/AJR.05.1427 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 098HE UT WOS:000241510800037 PM 17056929 ER PT J AU Weinand, C Peretti, GM Adams, SB Bonassar, LJ Randolph, MA Gill, TJ AF Weinand, Christian Peretti, Giuseppe M. Adams, Samuel B., Jr. Bonassar, Lawrence J. Randolph, Mark A. Gill, Thomas J. TI An allogenic cell-based implant for meniscal lesions SO AMERICAN JOURNAL OF SPORTS MEDICINE LA English DT Article; Proceedings Paper CT Interim Meeting of the American-Orthopaedic-Society-for-Sports-Medicine (AOSSM) CY FEB, 2005 CL Washington, DC SP Amer Orthopaed Soc Sports Med DE meniscus; repair; implant; autologous; allogenic; chondrocytes; tissue engineering; large-animal study ID AUTOLOGOUS CHONDROCYTE TRANSPLANTATION; ARTHROSCOPIC REPAIR; ARTICULAR-CARTILAGE; AVASCULAR ZONE; TISSUE; TEARS; KNEE; FIBROCARTILAGE; MENISCECTOMY; MATRIX AB Background: Meniscal tears in the avascular zones do not heal. Although tissue-engineering approaches using cells seeded onto scaffolds could expand the indication for meniscal repair, harvesting autologous cells could cause additional trauma to the patient. Allogenic cells, however, could provide an unlimited amount of cells. Hypothesis: Allogenic cells from 2 anatomical sources can repair lesions in the avascular region of the meniscus. Study Design: Controlled laboratory study. Methods: Both autologous and allogenic chondrocytes were seeded onto a Vicryl mesh scaffold and sutured into a bucket-handle lesion created in the medial menisci of 17 swine. Controls consisted of 3 swine knees treated with unseeded implants and controls from a previous experiment in which 4 swine were treated with suture only and 4 with no treatment. Menisci were harvested after 12 weeks and evaluated histologically for new tissue and percentage of interface healing surface; they were also evaluated statistically. Results: The lesions were closed in 15 of 17 menisci. None of the control samples demonstrated healing. Histologic analysis of sequential cuts through the lesion showed formation of new scar-like tissue in all experimental samples. One of 8 menisci was completely healed in the allogenic group and 2 of 9 in the autologous group; the remaining samples were partially healed in both groups. No statistically significant differences in the percentage of healing were observed between the autologous and allogenic cell-based implants. Conclusion: Use of autologous and allogenic chondrocytes delivered via a biodegradable mesh enhanced healing of avascular meniscal lesions. Clinical Relevance: This study demonstrates the potential of a tissue-engineered cellular repair of the meniscus using autologous and allogenic chondrocytes. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg,Lab Musculoskeletal Tissue En, Boston, MA 02114 USA. Univ Vita Salute, Hosp San Raffaele, Milan, Italy. Cornell Univ, Sibley Sch Mech & Aerosp Engn, Ithaca, NY 14853 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Plast Surg,Plast Surg Res Lab, Cambridge, MA 02138 USA. RP Gill, TJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Orthopaed Surg,Lab Musculoskeletal Tissue En, WACC 531,15 Parkman St, Boston, MA 02114 USA. EM tgill@partners.org RI Bonassar, Lawrence/C-2103-2016; Peretti, Giuseppe/K-6358-2016 OI Bonassar, Lawrence/0000-0003-1094-6433; Peretti, Giuseppe/0000-0001-9341-7187 NR 38 TC 41 Z9 46 U1 1 U2 6 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0363-5465 J9 AM J SPORT MED JI Am. J. Sports Med. PD NOV PY 2006 VL 34 IS 11 BP 1779 EP 1789 DI 10.1177/0363546506290666 PG 11 WC Orthopedics; Sport Sciences SC Orthopedics; Sport Sciences GA 103WB UT WOS:000241916800008 PM 16870819 ER PT J AU Stewart, L Grifiss, JM Jarvis, GA Way, LW AF Stewart, Lygia Grifiss, J. McLeod Jarvis, Gary A. Way, Lawrence W. TI Biliary bacterial factors determine the path of gallstone formation SO AMERICAN JOURNAL OF SURGERY LA English DT Article; Proceedings Paper CT 30th Annual Surgical Symposium of the Association-of-VA-Surgeons CY MAY 07-09, 2006 CL Cincinnati, OH DE gallstone formation; biofilm; slime; pigment stones; bacteria; beta-glucuronidase ID BROWN PIGMENT STONES; CHOLESTEROL GALLSTONES; BETA-GLUCURONIDASE; PATHOGENESIS; BILE; GLYCOCALYX; BIOFILMS; DISEASE; DNA AB Background: Bacteria cause pigment gallstones and can act as a nidus for cholesterol gallstone formation. Bacterial factors that facilitate gallstone formation include beta-glucuronidase (bG), phospholipase (PhL), and slime. The current study sought to determine whether bacterial factors influence the path of gallstone formation. Methods: A total of 382 gallstones were cultured and/or examined using scanning electron microscopy (SEM). Bacteria were tested for bG and slime production. Gallstone composition was determined using infrared spectrography. Ca-palmitate presence documented bacterial PhL production. Groups were identified based upon bacterial factors present: slime and bGPhL (slime/bGPhL), bGPhL only, and slime only. Influence of bacterial stone-forming factors on gallstone composition and morphology was analyzed. Results: Bacteria were present in 75% of pigment, 76% of mixed, and 20% of cholesterol stones. Gallstones with. bGPhL producing bacteria contained more pigment (71% vs. 26%, P < .0001). The slime/bGPhL group was associated (79%) with pigment stones, bGPhL was associated (56%) with mixed stones, while slime (or none) only was associated (67%) with cholesterol stones (P < .031, all comparisons). Conclusions: Bacterial properties determined the path of gallstone formation. Bacteria that produced all stone-forming factors promoted pigment stone formation, while those that produced only bGPhL promoted mixed stone formation. Bacteria that only produced slime lacked the ability to generate pigment solids, and consequently were more common in the centers of cholesterol stones. This shows how bacterial characteristics may govern the process of gallstone formation. (c) 2006 Excerpta Medica Inc. All rights reserved. C1 Univ Calif San Francisco, Vet Adm Med Ctr, Dept Surg, San Francisco, CA 94121 USA. San Francisco Vet Affairs Med Ctr, Surg Serv, San Francisco, CA USA. San Francisco Vet Affairs Med Ctr, Ctr Immunochem, San Francisco, CA USA. Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA. RP Stewart, L (reprint author), Univ Calif San Francisco, Vet Adm Med Ctr, Dept Surg, 4150 Clement St, San Francisco, CA 94121 USA. EM lygia.stewart@med.va.gov NR 30 TC 15 Z9 16 U1 1 U2 3 PU EXCERPTA MEDICA INC PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD NOV PY 2006 VL 192 IS 5 BP 598 EP 603 DI 10.1016/j.amjsurg.2006.08.001 PG 6 WC Surgery SC Surgery GA 102NW UT WOS:000241820000008 PM 17071191 ER PT J AU Lerwill, MF Young, RH AF Lerwill, Melinda F. Young, Robert H. TI Ovarian metastases of intestinal-type gastric carcinoma - A clinicopothologic study of 4 cases with contrasting features to those of the Krukenberg tumor SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE metastatic carcinoma; ovary; stomach ID PROGESTERONE-RECEPTORS; DIAGNOSTIC CHALLENGE; MUCINOUS TUMORS; ADENOCARCINOMAS; ESTROGEN; IMMUNOHISTOCHEMISTRY; DISTINCTION; PATTERNS; DIFFUSE AB Ovarian metastases of intestinal-type gastric adenocarcinomas are rare, and information on them is very limited compared with that on signet-ring cell carcinomas that result in the Krukenberg tumor. Four cases are reported herein. The patients averaged 55 years of age. In 3 patients, the ovarian metastases were identified several to 21 months after the diagnosis of the gastric primary, and the tumors were synchronous in the fourth. Two tumors were bilateral, 1 unilateral, and for 1, the laterality was unknown. The ovarian tumors were characteristically solid and cystic, with multinodular growth in 2. In 2 cases, the ovarian tumors had a pseudoendometrioid morphology with tubulo-glandular, cribriform, and papillary patterns; they also had focal trabecular and insular patterns. Prominent necrosis was present, including segmental and intraluminal "dirty" necrosis. In the other 2 cases, the ovarian tumors had a mucinous appearance, I being dominantly cystic with occasional goblet cells and the other with prominent foveolar-type cells. Nuclei ranged from deceptively bland to highly atypical. Surface implants were identified in 2 cases. Two ovarian tumors examined expressed cytokeratin 7 and 20 but not estrogen receptor. Three patients with follow-up information all died within I year of the ovarian metastases. Although information is limited, our results suggest that metastatic spread to the ovary by intestinal-type gastric adenocarcinoma is usually seen in patients older than those with Krukenberg tumors, with a known history of gastric carcinoma, and with concomitant widespread disease. Involvement of the ovary by intestinal-type gastric carcinoma produces a microscopic picture distinctly different from that of a Krukenberg tumor. These metastatic intestinal-type tumors may be confused with metastases from other gastrointestinal sites that are more frequently the cause of pseudoendometrioid or mucinous metastases, and like such tumors may be confused with primary ovarian endometrioid and mucinous neoplasms. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol,James Homer Wright Pathol Labs, Boston, MA 02114 USA. RP Lerwill, MF (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol,James Homer Wright Pathol Labs, Boston, MA 02114 USA. EM mlerwill@partners.org NR 23 TC 14 Z9 14 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD NOV PY 2006 VL 30 IS 11 BP 1382 EP 1388 DI 10.1097/01.pas.0000213256.75316.4a PG 7 WC Pathology; Surgery SC Pathology; Surgery GA 099RQ UT WOS:000241613500005 PM 17063077 ER PT J AU Higgins, RSD Fishman, JA AF Higgins, R. S. D. Fishman, J. A. TI Disparities in solid organ transplantation for ethnic minorities: Facts and solutions SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Editorial Material DE disparity; education; ethnicity; genomics; minority; race; transplantation ID KIDNEY ALLOGRAFT RECIPIENTS; RENAL-TRANSPLANTATION; LIVER-TRANSPLANTATION; SURROGATE MARKERS; RACIAL DISPARITIES; AMERICAN-INDIANS; ACCESS; SURVIVAL; DISEASE; TACROLIMUS AB The Diversity and Minority Affairs Committee of the American Society of Transplantation (AST) convened a symposium to examine organ transplantation in underserved and minority populations. The goals of the meeting included 'benchmarking' of solid organ transplantation among minority populations, review of the epidemiology of end-organ damage, exploration of barriers to transplantation services and development of approaches to eliminate disparities. Participants noted that minority populations were more likely to be adversely affected by limited preventive medical care, lack of counseling regarding transplant options, and delays in transplant referrals for organ transplantation. These features largely reflect economic disadvantage as well as the reduced presence of minority professionals with training in transplant-related specialties. Participants in the conference noted that recent changes in organ allocation policies had improved access to minority individuals once listed for renal transplantation. Similar advances will be needed for other organs to address inequities in pretransplant care and underrepresentation of minorities among transplant professionals. The biologic basis of differences in transplant outcomes for minority recipients has not been adequately studied. Research funds must be targeted to address biologic mechanisms underlying disparate transplant outcomes including the impacts of environment, education, poverty and lifestyle choices. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Rush Univ, Med Ctr, Dept Cardiovasc & Thorac Surg, Chicago, IL 60612 USA. RP Fishman, JA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. EM jfishman@partners.org NR 54 TC 51 Z9 51 U1 1 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD NOV PY 2006 VL 6 IS 11 BP 2556 EP 2562 DI 10.1111/j.1600-6143.2006.01514.x PG 7 WC Surgery; Transplantation SC Surgery; Transplantation GA 094LK UT WOS:000241240700008 PM 16952299 ER PT J AU Roth, AE Sonmez, T Unver, MU Delmonico, FL Saidman, SL AF Roth, A. E. Soenmez, T. Uenver, M. U. Delmonico, F. L. Saidman, S. L. TI Utilizing list exchange and nondirected donation through 'Chain' paired kidney donations SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE kidney exchange; kidney transplantation; list exchange; non-directed donor; optimal matching; paired kidney donation ID DONOR; TRANSPLANTATION; PROGRAM; CANDIDATES AB In a list exchange (LE), the intended recipient in an incompatible pair receives priority on the deceased donor waitlist (DD-waitlist) after the paired incompatible donor donates a kidney to a DD-waitlist candidate. A nondirected donor's (ND-D) kidney is usually transplanted directly to a DD-waitlist candidate. These two established practices would help even more transplant candidates if they were integrated with kidney paired donation (KPD). We consider a scenario in which the donor of an LE intended recipient (LE-IR) donates to a compatible KPD intended recipient (KPD-IR), and the KPD donor (KPD-D) donates to the waitlist (an LE-chain). We consider a similar scenario in which an ND-D donates to a KPD-IR and the KPD-D donates to the DD-waitlist (an ND-chain). Using data derived from the New England Program for Kidney Exchange (NEPKE) and from OPTN/SRTR recipient-donor distributions, simulations are presented to evaluate the potential impact of chain exchanges coordinated with KPD. LE donors (LE-D) and ND-D who are ABO-O result in the highest number of additional transplants, while results for ABO-A and B donors are similar to each other. We recommend that both LE and ND donations be utilized through chain exchanges. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Dept Econ, Cambridge, MA 02138 USA. Harvard Univ, Sch Business, Boston, MA 02163 USA. Boston Coll, Dept Econ, Chestnut Hill, MA 02167 USA. Univ Pittsburgh, Dept Econ, Pittsburgh, PA 15260 USA. New England Organ Bank Inc, Newton, MA USA. RP Saidman, SL (reprint author), Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. EM ssaidman@partners.org RI annie, annie/N-4756-2014 NR 22 TC 65 Z9 67 U1 0 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD NOV PY 2006 VL 6 IS 11 BP 2694 EP 2705 DI 10.1111/j.1600-6143.2006.01515.x PG 12 WC Surgery; Transplantation SC Surgery; Transplantation GA 094LK UT WOS:000241240700023 PM 16981911 ER PT J AU Chenine, AL Shai-Kobiler, E Steele, LN Augostini, P Ruprecht, RM Evan Secor, W AF Chenine, Agnes-Laurence Shai-Kobiler, Ela Steele, Lisa N. Augostini, Peter Ruprecht, Ruth M. Evan Secor, W. TI Schistosoma mansoni infection increases susceptibility to aids virus infection transmission and replication in non-human primates SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 Harvard Med Sch, Dana Farber Canc Inst, Dept Med, Atlanta, GA USA. Harvard Med Sch, Dana Farber Canc Inst, Dept Med, Boston, MA USA. Ctr Dis Control & Prevent, Atlanta, GA USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2006 VL 75 IS 5 SU S MA 27 BP 8 EP 8 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 109XW UT WOS:000242343900028 ER PT J AU Falade, CO Mokuolu, O Okafor, H Orogade, A Falade, A Adedoyin, O Oguonu, TM Hamer, DH Callahan, MV AF Falade, Catherine O. Mokuolu, Olugbenga Okafor, Henrietta Orogade, Adeola Falade, Adegoke Adedoyin, O. Oguonu, Tagbo M. Hamer, Davidson H. Callahan, Michael V. TI Epidemiology of congenital malaria in Nigeria: A multi-centre study SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 Univ Coll Ibadan Hosp, Dept Clin Pharmacol, Ibadan, Nigeria. Univ Ilorin, Teaching Hosp, Dept Paediat, Ilorin, Nigeria. Univ Nigeria, Teaching Hosp, Dept Paediat, Enugu, Nigeria. Ahmadu Bello Univ, Teaching Hosp, Dept Paediat, Kaduna, Nigeria. Univ Coll Ibadan Hosp, Dept Paediat, Ibadan, Nigeria. Boston Univ, Sch Publ Hlth, Ctr Int Hlth & Dev, Boston, MA USA. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2006 VL 75 IS 5 SU S MA 31 BP 9 EP 10 PG 2 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 109XW UT WOS:000242343900032 ER PT J AU Mokuolu, OA Falade, CO Okafor, HU Orogade, AA Adedoyin, OT Ernest, SK Dada-Adegbola, HO Oguonu, TA Mamman, AI Hamers, D Callahan, M AF Mokuolu, Olugbenga A. Falade, Catherine O. Okafor, Henrietta U. Orogade, Adeola A. Adedoyin, Olanrewaju T. Ernest, Samuel K. Dada-Adegbola, Hanah O. Oguonu, Tagbo A. Mamman, Aisha I. Hamers, Davidson Callahan, Michael TI Peripartum malaria in Nigeria: Current status and pregnancy outcome SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 Univ Ilorin, Teaching Hosp, Ilorin, Nigeria. Univ Coll Ibadan Hosp, Ibadan, Nigeria. Univ Nigeria, Teaching Hosp, Enugu, Nigeria. Ahmadu Bello Univ, Teaching Hosp, Zaria, Nigeria. Boston Univ, Ctr Int Hlth & Dev, Boston, MA USA. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2006 VL 75 IS 5 SU S MA 86 BP 26 EP 26 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 109XW UT WOS:000242343900087 ER PT J AU Okafor, HU Falade, CO Mokuolu, OA Orogade, AA Oguonu, TA Dada-Adegbola, HO Adedoyin, OT Mamman, AI Callahan, MV Hamer, DH AF Okafor, Henrietta U. Falade, Catherine O. Mokuolu, Olugbenga A. Orogade, A. A. Oguonu, Tagbo A. Dada-Adegbola, H. O. Adedoyin, O. T. Mamman, A. I. Callahan, M. V. Hamer, D. H. TI Use of malaria preventive measures in pregnancy and placental/neonatal parasitaemia: A multicentre baseline evaluation in Nigeria SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 Univ Nigeria, Teaching Hosp, Enugu, Nigeria. Univ Coll Ibadan Hosp, Ibadan, Nigeria. Univ Ilorin, Teaching Hosp, Ilorin, Nigeria. Univ Teaching Hosp, Kaduna, Nigeria. Univ Ilorin, Teaching Hosp, Ilorin, Nigeria. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Boston Univ, Sch Publ Hlth, Ctr Int Hlth Dev, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2006 VL 75 IS 5 SU S MA 85 BP 26 EP 26 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 109XW UT WOS:000242343900086 ER PT J AU LaRocque, RC Harris, JB Krastins, B Ryan, ET Sarracino, D Qadri, F Calderwood, SB AF LaRocque, Regina C. Harris, Jason B. Krastins, Bryan Ryan, Edward T. Sarracino, David Qadri, Firdausi Calderwood, Stephen B. TI Proteomic analysis of in vivo expressed and immunogenic proteins of Vibrio cholerae SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA USA. Harvard Partners Ctr Genet & Genom, Boston, MA USA. Int Ctr Diarrheal Dis Res, Dhaka, Bangladesh. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2006 VL 75 IS 5 SU S MA 290 BP 84 EP 84 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 109XW UT WOS:000242343900291 ER PT J AU Rollenhagen, JE Kalsy, A Saksena, R Qadri, F Calderwood, SB Kovac, P Wade, W Ryan, ET AF Rollenhagen, Julianne E. Kalsy, Anuj Saksena, Rina Qadri, Firdausi Calderwood, Stephen B. Kovac, Paul Wade, William Ryan, Edward T. TI Transcutaneous immunization with a neoglycoconjugate containing a Vibrio cholerae hexasaccharide derived from V-cholerae O1 Ogawa lipopolysaccharide bound to a protein carrier SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Div Infect Dis, Boston, MA USA. NIH, NIDDK, LMC Carbohydrates, Bethesda, MD USA. B Ctr Hlth Populat Studies, Int Ctr Diarrhoel Dis Res, Dhaka, Bangladesh. Dartmouth Med Sch, Hanover, NH USA. NR 0 TC 2 Z9 2 U1 0 U2 0 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 NOV PY 2006 VL 75 IS 5 SU S MA 291 BP 84 EP 85 PG 2 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 109XW UT WOS:000242343900292 ER PT J AU Riscoe, M Winter, R Kelly, J Smilkstein, M Dodean, R Hinrichs, D AF Riscoe, Michael Winter, Rolf Kelly, Jane Smilkstein, Martin Dodean, Rosie Hinrichs, Dave TI Evaluation and lead optimization of antimalarial aromatic ketones SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 Portland VA Med Ctr, Portland, OR USA. NR 0 TC 3 Z9 3 U1 1 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 NOV PY 2006 VL 75 IS 5 SU S MA 336 BP 97 EP 98 PG 2 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 109XW UT WOS:000242343900337 ER PT J AU Smilkstein, M Kelly, J Dodean, R Hinrichs, D Winter, R Riscoe, M AF Smilkstein, Martin Kelly, Jane Dodean, Rosie Hinrichs, David Winter, Rolf Riscoe, Michael TI Novel antimalarial acridone derivatives with both intrinsic potency and synergy with selected quinolines: In vitro and in vivo studies SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 Portland VA Med Ctr, Portland, OR USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 NOV PY 2006 VL 75 IS 5 SU S MA 337 BP 98 EP 98 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 109XW UT WOS:000242343900338 ER PT J AU Orogade, A Okafor, H Falade, C Mokuolu, O Mamman, A Oguonu, T Adegbola, H Ernest, S Callahan, M Hamer, D AF Orogade, Adeola Okafor, Henrietta Falade, Catherine Mokuolu, Olugbenga Mamman, Aisha Oguonu, Tagbo Adegbola, Hannah Ernest, Samuel Callahan, Michael Hamer, Davidson TI Clinical and laboratory features of congenital malaria in Nigeria SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 ABU Teaching Hosp, Kaduna, Nigeria. Univ Nigeria, Teaching Hosp, Enugu, Nigeria. Univ Coll Ibadan Hosp, Ibadan, Nigeria. Univ Ilorin, Teaching Hosp, Ilorin, Nigeria. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA USA. Boston Univ, Ctr Internat Hlth & Dev, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2006 VL 75 IS 5 SU S MA 423 BP 123 EP 124 PG 2 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 109XW UT WOS:000242343900424 ER PT J AU Peniche, AG Osorio, Y Melby, PC Travi, BL AF Peniche, Alex G. Osorio, Yaneth Melby, Peter C. Travi, Bruno L. TI Neutrophil infiltration is associated with initial parasite control but subsequently contributes to tissue damage in hamsters infected with leishmania (viannia) panamensis SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 Ctr Int Entrenamiento Invest Med, Cali, Colombia. S Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2006 VL 75 IS 5 SU S MA 506 BP 148 EP 148 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 109XW UT WOS:000242343900507 ER PT J AU Burgess, S Andrews, S Liebman, K Kelly, J Peyton, D AF Burgess, Steven Andrews, Simeon Liebman, Katherine Kelly, Jane Peyton, David TI Syntheses and evaluations of reversed chloroquines SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 Portland State Univ, Portland, OR 97207 USA. Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2006 VL 75 IS 5 SU S MA 540 BP 157 EP 157 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 109XW UT WOS:000242343900541 ER PT J AU Peyton, DH Burgess, S Liebman, K Kelly, J Andrews, S AF Peyton, David H. Burgess, Steven Liebman, Katherine Kelly, Jane Andrews, Simeon TI Reversed chloroquines: An update on molecules designed to subvert chloroquine resistance in P-falciparum SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 Portland State Univ, Portland, OR 97207 USA. Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2006 VL 75 IS 5 SU S MA 539 BP 157 EP 157 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 109XW UT WOS:000242343900540 ER PT J AU Osorio, Y Zhao, WG Travi, BL Hawel, L Saldarriaga, OA Espitia, C Melby, PC AF Osorio, Yaneth Zhao, Weiguo Travi, Bruno L. Hawel, Leo Saldarriaga, Omar A. Espitia, Claudia Melby, Peter C. TI Arginine metabolism in macrophages determines the outcome in experimental visceral leishmaniasis SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 Univ Texas, Hlth Sci Ctr, S Texas Vet Hlth Care Syst, San Antonio, TX 78285 USA. Univ Calif Riverside, Riverside, CA 92521 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2006 VL 75 IS 5 SU S MA 650 BP 187 EP 188 PG 2 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 109XW UT WOS:000242343901085 ER PT J AU Anstead, GM Zhang, Q Melby, PC AF Anstead, Gregory M. Zhang, Qiong Melby, Peter C. TI Nutrikine dysregulation: A new paradigm for the immunodeficiency of malnutrition SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 S Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2006 VL 75 IS 5 SU S MA 786 BP 227 EP 227 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 109XW UT WOS:000242343901221 ER PT J AU Kelly, JX Smilkstein, M Winter, R Doclean, R Hinrichs, D Riscoe, M AF Kelly, Jane X. Smilkstein, Martin Winter, Rolf Doclean, Rosie Hinrichs, Dave Riscoe, Mike TI Orally active acridones as novel and potent antimalarial chemotypes SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2006 VL 75 IS 5 SU S MA 870 BP 250 EP 251 PG 2 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 109XW UT WOS:000242343901305 ER PT J AU Kelly, JX Smilkstein, M Winter, R Dodean, R Riscoe, M AF Kelly, Jane X. Smilkstein, Martin Winter, Rolf Dodean, Rosie Riscoe, Mike TI Structure-activity relationships of orally active antimalarial acridones: Synthesis, optimization, and biological activity SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2006 VL 75 IS 5 SU S MA 872 BP 251 EP 251 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 109XW UT WOS:000242343901307 ER PT J AU Steele, LN Chenine, AL Augostini, P Shai-Kobiler, E Ruprecht, RM Secor, WE AF Steele, Lisa N. Chenine, Agnes-Laurence Augostini, Peter Shai-Kobiler, Ela Ruprecht, Ruth M. Secor, W. Evan TI Increased expression of chemokine receptors and activation markers on CD4(+) T cells during schistosome infection is associated with enhanced SHIV replication in co-infected macaques SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 Ctr Dis Control & Prevent, Atlanta, GA USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2006 VL 75 IS 5 SU S MA 954 BP 274 EP 274 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 109XW UT WOS:000242343901389 ER PT J AU Rollins, SM Peppercorn, A Young, J Drysdale, M Baresch-Bernal, A Bikowski, M Ashford, D Quinn, C Hillman, J Handfield, M Lyons, R Koehler, T Calderwood, SB Ryan, ET AF Rollins, Sean M. Peppercorn, Amanda Young, John Drysdale, Melissa Baresch-Bernal, Andrea Bikowski, Margaret Ashford, David Quinn, Conrad Hillman, Jeffrey Handfield, Martin Lyons, Rick Koehler, Theresa Calderwood, Stephen B. Ryan, Edward T. TI The identification of in vivo induced protein antigens during Bacillus Anthracis SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ New Mexico, Ctr Hearing Sci, Albuquerque, NM USA. Ctr Dis Control & Prevent, Atlanta, GA USA. Univ Florida, Gainesville, FL USA. Univ New Mexico, Hlth Sci Ctr, Albuquerque, NM USA. Univ Texas, Sch Med, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 NOV PY 2006 VL 75 IS 5 SU S MA 1067 BP 308 EP 308 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 109XW UT WOS:000242343901502 ER PT J AU Glickstein, LJ Coburn, JL AF Glickstein, Lisa J. Coburn, Jenifer L. TI Short report: Association of macrophage inflammatory response and cell death after in vitro Borrelia burgdorferi infection with arthritis resistance SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID NECROSIS-FACTOR-ALPHA; LYME-DISEASE; IXODES-SCAPULARIS; CYTOKINE RESPONSE; MICE; SUSCEPTIBILITY; ACTIVATION; INDUCTION; PATHOGEN; GAMMA AB Susceptibility to Borrelia burgdorferi infection and subsequent arthritis is genetically determined in mice and determined by innate immunity. Accordingly, macrophage responses to B. burgdorferi challenge may differ between mouse strains. Bone marrow-derived macrophages were infected ex vivo with clonal B. burgdorferi strain N40. Interleukin-12 and tumor necrosis factor-alpha (TNF-alpha) production were higher in macrophages from resistant C57B1/6 mice than in macrophages from susceptible C3H/HeJ mice. However, TNF-a production was observed in lower concentrations in C3H/HeJ (toll-like receptor-4(-/-)) macrophages than in C3H/FeJ (TLR4(+/+)) macrophages, suggesting that TLR4 might contribute to the response to B. burgdorferi. A higher cytokine response to B. burgdorferi was associated with cell death in macrophages from resistant C57B1/6 mice. Understanding variability in the response of macrophages to B. burgdorferi may contribute to understanding Lyme arthritis. C1 Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. Tufts Univ, New England Med Ctr, Div Geog Med & Infect Dis, Boston, MA 02111 USA. RP Glickstein, LJ (reprint author), Massachusetts Gen Hosp, 149 13th St,Room 8301, Charlestown, MA 02129 USA. EM lglickstein@partners.org; jcoburn@tufts-nemc.org FU NIAID NIH HHS [AI-40938, AI-051407]; NIDDK NIH HHS [1 P30DK39428] NR 22 TC 8 Z9 8 U1 0 U2 0 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 NOV PY 2006 VL 75 IS 5 BP 964 EP 967 PG 4 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 107RQ UT WOS:000242189100035 PM 17123997 ER PT J AU Khuri, SF AF Khuri, Shukri F. TI Safety, quality, and the national surgical quality improvement program SO AMERICAN SURGEON LA English DT Article; Proceedings Paper CT Conference on Contemporary Surgical Quality, Safety and Transparency CY JUN 05-06, 2006 CL Louisville, KY ID OF-VETERANS-AFFAIRS; OUTCOMES; ANESTHESIA; CARE AB The Institute of Medicine 1999 publication, To Err is Human, focused attention on preventable provider errors in surgery, and prompted numerous new national initiatives to improve patient safety. It is uncertain whether these initiatives have actually improved patient safety, mainly because of the lack of a quantitative metric for the assessment of patient safety in surgery. A 15-year experience with the National Surgical Quality Improvement Program, which originated in the Veteran's Administration in 1991 and was recently made available to the private sector, prompts the surgical community to place patient safety in surgery within a much larger conceptual framework than that of the Institute of Medicine report, and provides a quantitative metric for the assessment of patient safety initiatives. This conceptual framework defines patient safety in surgery as safety from all adverse outcomes (not only preventable errors and sentinel events); regards safety as an integral part of quality of surgical care; recognizes that adverse outcomes, and hence patient safety, are primarily determined by quality of systems of care; and uses comparative riskadjusted outcome data as a metric for the identification of system problems and for the assessment and improvement of patient safety from adverse outcomes. C1 VA Boston Healthcare Syst, Surg Serv 112, W Roxbury, MA 02132 USA. RP Khuri, SF (reprint author), VA Boston Healthcare Syst, Surg Serv 112, 1400 VFW Pkwy, W Roxbury, MA 02132 USA. NR 13 TC 43 Z9 44 U1 0 U2 2 PU SOUTHEASTERN SURGICAL CONGRESS PI ATLANTA PA 141 WEST WIEUCA RD, STE B100, ATLANTA, GA 30342 USA SN 0003-1348 J9 AM SURGEON JI Am. Surg. PD NOV PY 2006 VL 72 IS 11 SI SI BP 994 EP 998 PG 5 WC Surgery SC Surgery GA 102YY UT WOS:000241850900004 PM 17120939 ER PT J AU Hutter, MM AF Hutter, Matthew M. TI Does outcomes research impact quality? Examples from bariatric surgery SO AMERICAN SURGEON LA English DT Article; Proceedings Paper CT Conference on Contemporary Surgical Quality, Safety and Transparency CY JUN 05-06, 2006 CL Louisville, KY ID WEIGHT-LOSS SURGERY; ROUX-EN-Y; OPEN GASTRIC BYPASS; PRACTICE RECOMMENDATIONS; PRACTICE GUIDELINES; MORBID-OBESITY; SURGICAL-PROCEDURES; OF-LIFE; CARE; MORTALITY AB This manuscript addresses the question "Does outcomes research affect quality?" using examples from the field of bariatric surgery. The roles that outcomes research has played in each of the four major recent events in bariatric surgery are examined. In the first three major events, which include 1) the National Institutes of Health Consensus Conference on Bariatric Surgery in 1991, 2) the dramatic increase in numbers of bariatric operations performed, and 3) the move toward a laparoscopic approach in bariatric surgery, a multitude of outcomes studies seem to be the result, but not the cause, of these changes in the field of bariatric surgery. However, for the most recent event, the 2006 Centers for Medicare and Medicaid Services National Coverage Determination for bariatric surgery and the introduction of accreditation in general surgery, outcomes research has played a significant role in the determination of policy and, ultimately, quality. C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Hutter, MM (reprint author), Massachusetts Gen Hosp, Dept Surg, 15 Parkman St,ACC 335, Boston, MA 02114 USA. NR 47 TC 10 Z9 10 U1 1 U2 2 PU SOUTHEASTERN SURGICAL CONGRESS PI ATLANTA PA 141 WEST WIEUCA RD, STE B100, ATLANTA, GA 30342 USA SN 0003-1348 J9 AM SURGEON JI Am. Surg. PD NOV PY 2006 VL 72 IS 11 SI SI BP 1055 EP 1060 PG 6 WC Surgery SC Surgery GA 102YY UT WOS:000241850900015 PM 17120949 ER PT J AU Guenat, OT Generelli, S de Rooij, NF Koudelka-Hep, M Berthiaume, F Yarmush, ML AF Guenat, Olivier T. Generelli, Silvia de Rooij, Nicolaas F. Koudelka-Hep, Milena Berthiaume, Francois Yarmush, Martin L. TI Development of an array of ion-selective microelectrodes aimed for the monitoring of extracellular ionic activities SO ANALYTICAL CHEMISTRY LA English DT Article ID AMMONIUM IONOPHORE; BULK OPTODES; ELECTRODES; POLYMER; SENSORS; COEFFICIENTS; MEMBRANES; NONACTIN; PLATFORM; LIMITS AB In this study, we present the development and the characterization of a generic platform for cell culture able to monitor extracellular ionic activities (K+, NH4+) for real-time monitoring of cell-based responses, such as necrosis, apoptosis, or differentiation. The platform for cell culture is equipped with an array of 16 silicon nitride micropipet-based ion-selective microelectrodes with a diameter of either 2 or 6 mu m. This array is located at the bottom of a 200-mu m- wide and 350-mu m-deep microwell where the cells are cultured. The characterization of the ion-selective microelectrode arrays in different standard and physiological solutions is presented. Near-Nernstian slopes were obtained for potassium- (58.6 +/- 0.8 mV/pK, n = 15) and ammonium-selective microelectrodes (59.4 +/- 3.9 mV/pNH(4), n = 13). The calibration curves were highly reproducible and showed an average drift of 4.4 +/- 2.3 mV/h (n = 10). Long-term behavior and response after immersion in physiological solutions are also presented. The lifetime of the sensors was found to be extremely long with a high recovery rate. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med, Boston, MA 02114 USA. Univ Neuchatel, Inst Microtechnol, SAMLAB, CH-2002 Neuchatel, Switzerland. RP Guenat, OT (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Engn Med, Boston, MA 02114 USA. EM olivier.guenat@unine.ch OI Guenat, Olivier/0000-0003-1103-9712 FU NIBIB NIH HHS [P41EB002503, P41 EB002503, P41 EB002503-05]; NIDDK NIH HHS [R01 DK043371, R01 DK043371-13, R01DK43371] NR 35 TC 17 Z9 17 U1 1 U2 12 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD NOV 1 PY 2006 VL 78 IS 21 BP 7453 EP 7460 DI 10.1021/ac0609733 PG 8 WC Chemistry, Analytical SC Chemistry GA 100LG UT WOS:000241670000027 PM 17073412 ER PT J AU Gilbert, RJ Wedeen, VJ Magnusson, LH Benner, T Wang, RP Dai, G Napadow, VJ Roche, KK AF Gilbert, Richard J. Wedeen, Van J. Magnusson, Lee H. Benner, Thomas Wang, Ruopeng Dai, George Napadow, Vitaly J. Roche, Kenneth K. TI Three-dimensional myoarchitecture of the bovine tongue demonstrated by diffusion spectrum magnetic resonance imaging with tractography SO ANATOMICAL RECORD PART A-DISCOVERIES IN MOLECULAR CELLULAR AND EVOLUTIONARY BIOLOGY LA English DT Article DE lingual structural imaging; continuum model; lingual deformation; magnetic resonance imaging ID FIBER ARCHITECTURE; FIELD GRADIENT; SPIN ECHOES; MUSCLE; MORPHOLOGY; NMR; SPECTROSCOPY; ORIENTATION; MECHANICS; TENTACLES AB The anatomy of the mammalian tongue consists of an intricate array of variably aligned and extensively interwoven muscle fibers. As a result, it is particularly difficult to resolve the relationship between the tongue's microscopic anatomy and tissue-scale mechanical function. In order to address this question, we employed a method, diffusion spectrum imaging (DSI) with tractography, for displaying the macroscopic orientational properties of the tissue's constituting myofibers. DSI measures spatially variant proton displacement for a given 3D imaging segment (voxel), reflecting the principal orientation(s) of its myofibers. Tractography uses the angular similarity displayed by the principal fiber populations of multiple adjacent voxels to generate tract-like structures. DSI with tractography thus defines a unique set of tracts based on the net orientational behavior of the myofiber populations at different positions in the tissue. By this approach, we demonstrate a novel myoarchitectural pattern for the bovine tongue, consisting of short and orthogonally aligned crossing fiber tracts in the intrinsic core region, and longer, parallel-aligned fiber tracts on the tissue margins and in the regions of extrinsic fiber insertion. The identification of locally aligned myofiber populations by DSI with tractography allows us to reconsider lingual anatomy, not in conventional microscopic terms, but as a set of heterogeneously aligned and macroscopically resolved myofiber tracts. We postulate that the properties associated with these myofiber tracts predict the mechanical behavior of the tissue and thus constitute a method to relate structure and function for anatomically complex muscular tissues. C1 MIT, Dept Mech Engn, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. RP Gilbert, RJ (reprint author), MIT, Dept Mech Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM rgilbert@mit.edu NR 37 TC 26 Z9 29 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4884 J9 ANAT REC PART A JI Anat. Rec. Part A PD NOV PY 2006 VL 288A IS 11 BP 1173 EP 1182 DI 10.1002/ar.a.20387 PG 10 WC Anatomy & Morphology SC Anatomy & Morphology GA 104RN UT WOS:000241976600006 PM 17031810 ER PT J AU Mashour, GA Sandberg, WS AF Mashour, George A. Sandberg, Warren S. TI Craniocervical extension improves the specificity and predictive value of the Mallampati airway evaluation SO ANESTHESIA AND ANALGESIA LA English DT Article ID DIFFICULT TRACHEAL INTUBATION; CLINICAL SIGN AB BACKGROUND: The modified Mallampati (MMP) classification is a standard airway examination that assesses mouth opening and structures within the oral cavity. Recent data suggest that maximal mouth opening (as measured by interdental distance) is possible only with extension of the craniocervical junction. Because the MMP examination is performed with the head in a neutral position, the airway may appear worse because of submaximal interdental distance. We hypothesized that adding craniocervical extension to the MMP would allow for greater mouth opening, lower scores, and less false positives than the traditional MMP examination. METHODS: Multiple clinicians with at least 1 yr of airway experience evaluated adult airways (n = 60) with the MMP examination (with head in neutral position). The same examination was then repeated with the addition of craniocervical extension (Extended Mallampati Score, EMS). RESULTS: On average, craniocervical extension decreased the MMP class (P < 0.002). The EMS improved specificity from 70% to 80% and positive predictive value from 24% to 31% when compared with the traditional MMP. The sensitivity (83%) was the same for MMP and EMS. CONCLUSIONS: Craniocervical extension improves the specificity and positive predictive value of the MMP airway evaluation while retaining sensitivity of the traditional MMP examination. The introduction of the EMS into clinical practice should be considered. C1 Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Anaesthesia, Boston, MA 02115 USA. RP Mashour, GA (reprint author), 55 Fruit St,Clin 309, Boston, MA 02114 USA. EM gmashour@partners.org OI Sandberg, Warren/0000-0002-9246-777X NR 10 TC 9 Z9 11 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD NOV PY 2006 VL 103 IS 5 BP 1256 EP 1259 DI 10.1213/01.ane.0000237402.03329.3b PG 4 WC Anesthesiology SC Anesthesiology GA 099CR UT WOS:000241570600032 PM 17056964 ER PT J AU Oren, E Chegini, S Hamilos, DL AF Oren, Eyal Chegini, Soheil Hamilos, Daniel L. TI Ultrarush venom desensitization after systemic reactions during conventional venom immunotherapy SO ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY LA English DT Article ID HYMENOPTERA VENOM; INSECT HYPERSENSITIVITY; CONTROLLED TRIAL; PRETREATMENT; EFFICACY; ALLERGY; SAFETY AB Background: Rush and ultrarush venom immunotherapy (VIT) protocols are safe and effective in patients with Hymenoptera hypersensitivity. However, these protocols have typically been used instead of conventional VIT and not in patients who have experienced adverse reactions during conventional VIT. To date, there are no reports of using an ultrarush VIT protocol to desensitize patients with a history of severe systemic reactions during conventional VIT. Objective: To determine whether ultrarush VIT can be safely administered to a high-risk patient with a history of severe systemic reactions to conventional VIT. Methods: Premedication with 40 mg of prednisone, 180 mg of fexofenadine, and 150 mg of ranitidine orally twice daily was initiated. The patient received VIT to mixed vespid and wasp in a medical intensive care unit via a 13-step buildup on day I followed by a 2-step buildup on day 2. Immunotherapy was begun with a dose of 0.005 mu g of mixed vespid and 0.002 mu g of wasp venom and achieved a total dose of 300 mu g of mixed vespid and 100 mu g of wasp venom. Results: The patient tolerated the procedure with minimal adverse effects. She subsequently received maintenance dosing in the outpatient clinic weekly for 4 weeks and bimonthly for 8 weeks, and she continues monthly maintenance VIT. Conclusions: We report the first successful use of ultrarush VIT in a high-risk patient with a history of severe systemic reactions during conventional VIT. This protocol should be considered in patients with a history of allergy to vespids or wasps who require VIT but cannot reach a maintenance dose with conventional VIT owing to systemic reactions. C1 Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. Penn State Univ, Milton S Hershey Med Ctr, Div Pulm Allergy & Crit Care Med, Hershey, PA 17033 USA. RP Oren, E (reprint author), Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, 55 Fruit St, Boston, MA 02114 USA. EM eoren@partners.org NR 17 TC 7 Z9 7 U1 0 U2 0 PU AMER COLL ALLERGY ASTHMA IMMUNOLOGY PI ARLINGTON HTS PA 85 WEST ALGONQUIN RD SUITE 550, ARLINGTON HTS, IL 60005 USA SN 1081-1206 J9 ANN ALLERG ASTHMA IM JI Ann. Allergy Asthma Immunol. PD NOV PY 2006 VL 97 IS 5 BP 606 EP 610 PG 5 WC Allergy; Immunology SC Allergy; Immunology GA 108ZR UT WOS:000242278200007 PM 17165267 ER PT J AU Jansen, AC Sancak, O D'Agostino, MD Badhwar, A Roberts, P Gobbi, G Wilkinson, R Melanson, D Tampieri, D Koenekoop, R Gans, M Maat-Kievit, A Goedbloed, M van den Ouweland, AMW Nellist, M Pandolfo, M McQueen, M Sims, K Thiele, EA Dubeau, F Andermann, F Kwiatkowski, DJ Halley, DJJ Andermann, E AF Jansen, An C. Sancak, Ozgur D'Agostino, Maria Daniela Badhwar, AmanPreet Roberts, Penelope Gobbi, Gabriella Wilkinson, Ralph Melanson, Denis Tampieri, Donatella Koenekoop, Robert Gans, Mark Maat-Kievit, Anneke Goedbloed, Miriam van den Ouweland, Ans M. W. Nellist, Mark Pandolfo, Massimo McQueen, Mary Sims, Katherine Thiele, Elisabeth A. Dubeau, Francois Andermann, Frederick Kwiatkowski, David J. Halley, Dicky J. J. Andermann, Eva TI Unusually mild Tuberous Sclerosis phenotype is associated with TSC2 R905Q mutation SO ANNALS OF NEUROLOGY LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; GERMLINE MUTATIONS; JAPANESE PATIENTS; CLINICAL-MANIFESTATIONS; UNRELATED PATIENTS; MONOZYGOTIC TWINS; MISSENSE MUTATION; HAMARTIN COMPLEX; GENE-PRODUCTS; GENOTYPE AB Objective: To report the clinical manifestations and functional aspects of Tuberous Sclerosis Complex (TSC), resulting from Codon 905 mutations in TSC2 gene. Methods: We performed a detailed study of the TSC phenotype and genotype in a large French-Canadian kindred (Family A). Subsequently, clinical and molecular data on 18 additional TSC families with missense mutations at the same codon of TSC2 were collected. Functional studies were performed on the different missense changes and related to the phenotype. Results: A 2714G > A (R905Q) mutation was identified in Family A. The TSC phenotype in this family was unusually mild and characterized by hypomelanotic macules or focal seizures that remitted spontaneously or were easily controlled with medication. Diagnostic criteria were met in only a minority of mutation carriers. Other families with the R905Q mutation were found to have a similar mild phenotype. In contrast, patients with a 2713C > T (R905W) or a 2713C > G (R905G) mutation had more severe phenotypes. Although all three amino acid substitutions were pathogenic, the R905W and R905G substitutions affected tuberin function more severely than R905Q Interpretation: Codon 905 missense mutations in TSC2 are relatively common. The TSC2 R905Q mutation is associated with unusually mild disease, consistent with functional studies. Combined with previous reports, it is apparent that certain TSC2 missense mutations are associated with a mild form of tuberous sclerosis, which in many patients does not meet standard diagnostic criteria. These findings have implications for the large number of patients with limited clinical features of TSC and for genetic counseling in these families. C1 McGill Univ, Montreal Neurol Hosp & Inst, Neurogenet Unit, Montreal, PQ, Canada. McGill Univ, Dept Neurol & Neurosurg, Montreal, PQ, Canada. Erasmus MC, Dept Clin Genet, Rotterdam, Netherlands. Brigham & Womens Hosp, Div Hematol, Boston, MA 02115 USA. Univ Montreal, Dept Psychiat, Montreal, PQ H3C 3J7, Canada. McGill Univ, Dept Psychiat, Montreal, PQ H3A 2T5, Canada. McGill Univ, Dept Dermatol, Montreal, PQ, Canada. McGill Univ, Dept Radiol, Montreal, PQ, Canada. Montreal Childrens Hosp, McGill Ocular Genet Lab, Montreal, PQ H3H 1P3, Canada. McGill Univ, Dept Ophthalmol, Montreal, PQ H3A 2T5, Canada. McGill Univ, Dept Human Genet, Montreal, PQ H3A 2T5, Canada. Free Univ Brussels, Dept Neurol, Brussels, Belgium. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pediat Neurol, Boston, MA USA. McGill Univ, Dept Pediat, Montreal, PQ H3A 2T5, Canada. RP Andermann, E (reprint author), Montreal Neurol Hosp & Inst, Neurogenet Unit, 3801 Univ St,Room 127, Montreal, PQ H3A 2B4, Canada. EM eva.andermann@mcgill.ca RI Pandolfo, Massimo/B-2853-2010; maat-kievit, anneke/C-7483-2013; Gobbi, Gabriella/I-2786-2013; Kievit, Anneke/O-8830-2014; Jansen, Anna/P-3121-2014 OI Jansen, Anna/0000-0002-3835-2824 FU PHS HHS [31535] NR 46 TC 48 Z9 51 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0364-5134 EI 1531-8249 J9 ANN NEUROL JI Ann. Neurol. PD NOV PY 2006 VL 60 IS 5 BP 528 EP 539 DI 10.1002/ana.21037 PG 12 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 112RQ UT WOS:000242545100008 PM 17120248 ER PT J AU Rosand, J AF Rosand, Jonathan TI Clinical course and prevention of intracerebral hemorrhage SO ANNALS OF NEUROLOGY LA English DT Meeting Abstract CT 131st Annual Meeting of the American-Neurological-Association CY OCT 08-11, 2006 CL Chicago, IL SP Amer Neurol Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD NOV PY 2006 VL 60 IS 5 BP 633 EP 633 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 112RQ UT WOS:000242545100050 ER PT J AU Sharma, N AF Sharma, Nutan TI Primary early onset generalized dystonia SO ANNALS OF NEUROLOGY LA English DT Meeting Abstract CT 131st Annual Meeting of the American-Neurological-Association CY OCT 08-11, 2006 CL Chicago, IL SP Amer Neurol Assoc C1 Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD NOV PY 2006 VL 60 IS 5 BP 634 EP 634 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 112RQ UT WOS:000242545100053 ER PT J AU De Jager, PL Compston, A Daly, M Hafler, D Haines, J Hauser, S AF De Jager, Philip L. Compston, Alastair Daly, Mark Hafler, David Haines, Jonathan Hauser, Stephen TI Whole genome association study in multiple sclerosis SO ANNALS OF NEUROLOGY LA English DT Meeting Abstract CT 131st Annual Meeting of the American-Neurological-Association CY OCT 08-11, 2006 CL Chicago, IL SP Amer Neurol Assoc C1 Univ Cambridge, Cambridge CB2 1TN, England. Massachusetts Gen Hosp, Boston, MA 02114 USA. Vanderbilt Univ, Nashville, TN 37240 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD NOV PY 2006 VL 60 IS 5 BP 641 EP 641 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 112RQ UT WOS:000242545100072 ER PT J AU Moy, B Tu, D Pater, JL Ingle, JN Shepherd, LE Whelan, TJ Goss, PE AF Moy, B. Tu, D. Pater, J. L. Ingle, J. N. Shepherd, L. E. Whelan, T. J. Goss, P. E. TI Clinical outcomes of ethnic minority women in MA.17: a trial of letrozole after 5 years of tamoxifen in postmenopausal women with early stage breast cancer SO ANNALS OF ONCOLOGY LA English DT Article DE early breast cancer; aromatase inhibitors; minority race; ethnicity ID EARLY MENOPAUSAL TRANSITION; AFRICAN-AMERICAN WOMEN; QUALITY-OF-LIFE; RANDOMIZED-TRIAL; SURVIVAL; AGE; PARTICIPATION; THERAPY; RACE; REPRESENTATION AB Background: Aromatase inhibitors are widely employed in the adjuvant treatment of early stage breast cancer. The impact of aromatase inhibitors has not been established in ethnic minority women. Patients and methods: The purpose of this study was to evaluate the impact of letrozole on minority women in MA.17, a placebo-controlled trial of letrozole following 5 years of tamoxifen in postmenopausal women with early stage breast cancer. Retrospective comparison of disease-free survival (DFS), side effects, and mean changes in quality of life (QOL) scores from baseline between Caucasian and minority women was performed. Results: Minority (n = 352) and Caucasian (n = 4708) women were analyzed. There was no difference between these groups in DFS (91.6% versus 92.4% respectively for 4 year DFS). Letrozole, compared with placebo, significantly improved DFS for Caucasians (HR = 0.55; P < 0.0001) but not for minorities (HR = 1.39; P = 0.53). Among women who received letrozole, minorities had a significantly lower incidence of hot flashes (49% versus 58%; P = 0.02), fatigue (29% versus 39%; P = 0.005), and arthritis (2% versus 7%; P = 0.006) compared with Caucasians. Mean change in QOL scores for minority women who received letrozole demonstrated improved mental health at the 6-month assessment (P = 0.02) and less bodily pain at the 12-month assessment (P = 0.046). Conclusion: Letrozole improved DFS in Caucasians but a definite benefit in minority women has not yet been demonstrated. Minority women tolerated letrozole better than Caucasians in terms of toxicity. These results need confirmation in other trials of aromatase inhibitors. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gillette Ctr Womens Canc, Boston, MA 02114 USA. Natl Canc Inst Canada Clin Trials Grp, Kingston, ON, Canada. Mayo Clin, Rochester, MN USA. McMaster Univ, Hamilton, ON, Canada. RP Moy, B (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gillette Ctr Womens Canc, 55 Fruit St,YAW 9A, Boston, MA 02114 USA. EM bmoy@partners.org RI Whelan, Timothy/D-3185-2017 NR 38 TC 24 Z9 24 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD NOV PY 2006 VL 17 IS 11 BP 1637 EP 1643 DI 10.1093/annonc/mdl177 PG 7 WC Oncology SC Oncology GA 102AV UT WOS:000241784000006 PM 16936184 ER PT J AU Ng, AK Li, S Neuberg, D Fisher, DC McMillan, C Silver, B Marcus, KC Stevenson, MA Mauch, PM AF Ng, A. K. Li, S. Neuberg, D. Fisher, D. C. McMillan, C. Silver, B. Marcus, K. C. Stevenson, M. A. Mauch, P. M. TI Long-term results of a prospective trial of mantle irradiation alone for early-stage Hodgkin's disease SO ANNALS OF ONCOLOGY LA English DT Article DE Hodgkin's disease; radiation therapy; late effects ID CONTROLLED CLINICAL-TRIALS; QUALITY-ASSURANCE PROGRAM; PROGNOSTIC-FACTORS; FOLLOW-UP; FDG-PET; LYMPHOMA; GALLIUM; IA; TOMOGRAPHY; MANAGEMENT AB Background: To determine the long-term treatment outcome and late effects of mantle irradiation alone in selected patients with early-stage Hodgkin's disease. Methods: Between 1988 and 2000, 87 patients with pathologic stage (Ann Arbor) I-IIA or clinical stage IA Hodgkin's disease were entered on to a prospective trial of mantle irradiation alone. Patients with B symptoms, large mediastinal adenopathy, or subcarinal or hilar involvement were excluded. The median doses to the mantle field and mediastinum were 36 Gy (range 30.3-40) and 38.6 Gy (range 30.6-44), respectively. The actuarial freedom from treatment failure (FFTF) and overall survival (OS) rates were calculated using the Kaplan-Meier technique. Results: The median follow-up was 107 months (range 23-192). Thirteen of 87 patients (15%) relapsed at a median of 30 months (range 5-62). The 5- and 10-year actuarial FFTF rates were 86% and 84.7%, respectively. All 13 patients who relapsed are alive without evidence of disease at a median of 84 months (range 30-156) post-salvage therapy. Five patients developed a second malignancy at a median of 93 months (range 27-131). The 10-year actuarial risk of a second malignancy was 4.5%. There have been two deaths to date, both due to second malignancies. The 10-year OS rate was 98.2%. Conclusion: In selected patients with early-stage Hodgkin's disease, mantle irradiation alone has an excellent long-term survival rate, comparing favorably with the previous standard treatment of extended-field radiation therapy and the current standard of combined modality therapy. C1 Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat Sci, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. Childrens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, Boston, MA 02215 USA. RP Mauch, PM (reprint author), 75 Francis St,ASB1-L2, Boston, MA 02115 USA. EM pmauch@lroc.harvard.edu NR 24 TC 2 Z9 2 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD NOV PY 2006 VL 17 IS 11 BP 1693 EP 1697 DI 10.1093/annonc/mdl288 PG 5 WC Oncology SC Oncology GA 102AV UT WOS:000241784000015 PM 17018702 ER PT J AU Deasy, J Lee, EK Bortfeld, T Langer, M Zakarian, K Alaly, J Zhang, Y Liu, H Mohan, R Ahuja, R Pollack, A Purdy, J Rardin, R AF Deasy, J. Lee, E. K. Bortfeld, T. Langer, M. Zakarian, K. Alaly, J. Zhang, Y. Liu, H. Mohan, R. Ahuja, R. Pollack, A. Purdy, J. Rardin, R. TI A collaboratory for radiation therapy treatment planning optimization research SO ANNALS OF OPERATIONS RESEARCH LA English DT Article DE radiation therapy treatment planning; intensity modulated radiation therapy; optimization ID INTENSITY-MODULATED RADIOTHERAPY; DIRECT APERTURE OPTIMIZATION; DOSE CALCULATION; DELIVERY AB Intensity modulated radiation therapy treatment planning (IMRTP) is a challenging application of optimization technology. We present software tools to facilitate IMRTP research by computational scientists who may not have convenient access to radiotherapy treatment planning systems. The tools, developed within Matlab and CERR (computational environment for radiotherapy research), allow convenient access, visualization, programmable manipulation, and sharing of patient treatment planning data, as well as convenient generation of dosimetric data needed as input for treatment plan optimization research. CERR/Matlab also provides a common framework for storing, reviewing, sharing, and comparing optimized dose distributions from multiple researchers. C1 Oncol Washington Univ, Dept Radiat, Div Bioinformat & Outcomes Res, St Louis, MO USA. Georgia Inst Technol, Atlanta, GA 30332 USA. Emory Univ, Atlanta, GA 30322 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Indiana Univ, Indianapolis, IN 46204 USA. Rice Univ, Houston, TX 77251 USA. UTMD Anderson Canc Ctr, Houston, TX USA. Univ Florida, Gainesville, FL USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Purdue Univ, W Lafayette, IN 47907 USA. RP Deasy, J (reprint author), Oncol Washington Univ, Dept Radiat, Div Bioinformat & Outcomes Res, St Louis, MO USA. EM deasy@wustl.edu OI Deasy, Joseph/0000-0002-9437-266X NR 24 TC 10 Z9 10 U1 0 U2 4 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0254-5330 J9 ANN OPER RES JI Ann. Oper. Res. PD NOV PY 2006 VL 148 IS 1 BP 55 EP 63 DI 10.1007/s10479-006-0079-7 PG 9 WC Operations Research & Management Science SC Operations Research & Management Science GA 113MX UT WOS:000242603100004 ER PT J AU Hillman, RE Heaton, JT Masaki, A Zeitels, SM Cheyne, HA AF Hillman, Robert E. Heaton, James T. Masaki, Asa Zeitels, Steven M. Cheyne, Harold A. TI Ambulatory monitoring of disordered voices SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article; Proceedings Paper CT Meeting of the American-Laryngological-Association CY MAY 19-20, 2006 CL Chicago, IL SP Amer Laryngol Assoc DE ambulatory monitoring; phonation; voice disorder ID SPEAKING TIME; ACCUMULATOR; SPEECH; VIBRATION AB Objectives: Recently developed systems for ambulatory monitoring of voice use employ miniature accelerometers placed at the base of the anterior neck to sense phonation. As it is hoped that such systems will help improve the clinical assessment and management of voice disorders, this study was undertaken to determine the impact of dysphonia severity on the accuracy of accelerometer-based estimates of vocal function. Methods: Simultaneous recordings were made of oral acoustic (microphone) and neck skin acceleration signals for 6 normal speakers and 18 patients with voice disorders (mild to severe dysphonia) as they performed several speech tasks. Measures of phonation time, fundamental frequency, and sound pressure level were extracted from the two types of signals and compared. Results: It was generally demonstrated that accelerometer-based measures closely approximated corresponding measurements obtained from a microphone signal across all levels of dysphonia severity. Furthermore, there was evidence that in some cases the accelerometer may actually represent a more robust approach for estimating phonation parameters in disordered voices. Conclusions: The results generally support the recent application of accelerometers as phonation sensors in ambulatory voice monitoring systems that can be used in the clinical assessment and management of voice disorders. C1 Harvard Univ, Sch Med, Ctr Laryngeal Surg & Voice Rehabil,Dept Surg, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. Harvard Mit Div Hlth Sci & Technol, Speech & Hearing Biosci & Technol Program, Boston, MA USA. RP Hillman, RE (reprint author), Ctr Laryngeal Surg & Voice Rehabil, 1 Bowdoin Sq,11th Floor, Boston, MA 02114 USA. FU NIDCD NIH HHS [R21DC05397] NR 14 TC 49 Z9 49 U1 0 U2 1 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 NOV PY 2006 VL 115 IS 11 BP 795 EP 801 PG 7 WC Otorhinolaryngology SC Otorhinolaryngology GA 106NS UT WOS:000242108200001 PM 17165660 ER PT J AU Bosso, JA Mauldin, PD Steed, LL AF Bosso, John A. Mauldin, Patrick D. Steed, Lisa L. TI Consequences of combining cystic fibrosis- and non-cystic fibrosis-derived Pseudomonas aeruginosa antibiotic susceptibility results in hospital antibiograms SO ANNALS OF PHARMACOTHERAPY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-College-of-Clinical-Pharmacy CY OCT 23-26, 2005 CL San Francisco, CA SP Amer Coll Clin Pharm DE antibiogram; Pseudomonas aeruginosa; resistance; susceptibility ID RESISTANCE; LUNG AB BACKGROUND: In preparing hospital antibiograms for individual organisms and antibiotics, laboratories often combine susceptibility data for isolates from a variety of sources and patient types. If results from patients with known resistance patterns that vary from normal are included, the overall susceptibility value for the institution could be misleadingly skewed. OBJECTIVE: To assess the degree of bias introduced into a hospital antibiogram by combining cystic fibrosis (CF) and non-CIF isolates of Pseudomonas aeruginosa to produce one hospital-wide percent susceptible figure for each tested antibiotic. METHODS: A retrospective analysis was conducted of an academic, tertiary care medical center's microbiology database. We examined quarterly and annual susceptibility data from 2004, comparing non-CF data with combined susceptibility data for 10 antibiotics within each quarter, as well as those reported in the annual antibiogram. Differences were assessed for statistical significance using chi(2) testing with Bonferroni correction. RESULTS: Large differences were observed between non-CIF and combined percent susceptible data in the 4 quarters (aminoglycosides 3% vs 20%, fluoroquinolones 2% vs 18%, respectively) and when comparing annual non-CF (n = 191) with annual combined (n = 266) data. With the annual figures, these differences were frequently statistically significant (70% vs 58%, 91% vs 83%, 85% vs 70%, and 72% vs 60% for gentamicin, tobramycin, amikacin, and gatifloxacin/levofloxacin, respectively; all p <= 0.01). CONCLUSIONS: Combining CIF and non-CIF P aeruginosa susceptibility into one percent susceptibility value for all isolates may produce figures that underestimate the activity of some antibiotic classes against non-CIF isolates. Clinicians may make less than optimal empiric antibiotic selection choices based on such data. C1 S Carolina Coll Pharm, Dept Pharm & Clin Sci, Charleston, SC 29425 USA. Med Univ S Carolina, Coll Med, Div Infect Dis, Columbia, SC 29208 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC USA. Med Univ S Carolina, Dept Pathol & Lab Med, Columbia, SC 29208 USA. RP Bosso, JA (reprint author), S Carolina Coll Pharm, Dept Pharm & Clin Sci, MUSC Campus,280 Calhoun St,Rm QF213C, Charleston, SC 29425 USA. EM bossoja@musc.edu NR 8 TC 9 Z9 10 U1 1 U2 1 PU HARVEY WHITNEY BOOKS CO PI CINCINNATI PA PO BOX 42696, CINCINNATI, OH 45242 USA SN 1060-0280 J9 ANN PHARMACOTHER JI Ann. Pharmacother. PD NOV PY 2006 VL 40 IS 11 BP 1946 EP 1949 DI 10.1345/aph.1H377 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 104OF UT WOS:000241967000005 PM 17018687 ER PT J AU O'Rourke, RW Seltman, AK Chang, EY Reavis, KM Diggs, BS Hunter, JG Jobe, BA AF O'Rourke, Robert W. Seltman, Ann K. Chang, Eugene Y. Reavis, Kevin M. Diggs, Brian S. Hunter, John G. Jobe, Blair A. TI A model for gastric banding in the treatment of morbid obesity - The effect of chronic partial gastric outlet obstruction on esophageal physiology SO ANNALS OF SURGERY LA English DT Article ID GASTROESOPHAGEAL-REFLUX DISEASE; HYPERTROPHIC SMOOTH-MUSCLE; OPOSSUM ESOPHAGUS; MANOMETRIC ABNORMALITIES; MOTILITY DISORDERS; BARIATRIC SURGERY; BODY-MASS; FOLLOW-UP; ACHALASIA; SYMPTOMS AB Objective: This work establishes an animal model for nonadjustable gastric banding and characterizes the effect of gastric banding on esophageal physiology. Summary Background Data: Obstruction at the esophagogastric junction (EGJ) results in esophageal dilation and aperistalsis. Although laparoscopic gastric banding as a primary treatment of morbid obesity has been widely accepted, the effects of this therapy on esophageal function remain unknown. Methods: Twenty-five opossums were randomly divided into sham (n = 5), EGJ band (n = 5), and gastric band (n = 15) groups. Gastric and EGJ bands were surgically placed, and esophageal manometry was performed prebanding, at 2-week intervals during the banding period (up to 14 weeks), and 2 and 4 weeks after band removal. Results: Manometric measures were equivalent prior to banding in all groups. There were no changes in LES or esophageal pressures during the study period in the sham group. During banding, there was a 36% decrease in baseline mean resting lower esophageal sphincter pressure in the gastric band group (P = 0.003). Mean distal esophageal peristaltic pressure decreased from baseline by 36% in gastric band animals (P < 0.001). The incidence of esophageal motility disorder during the study period for sham, EGJ band, and gastric band groups, was 2.9%, 42.1%, and 31.3%, respectively (P = 0.001, P = 0.381, pairwise comparisons of gastric band vs. sham and gastric band versus EGJ groups, respectively). Immediately prior to band removal, the probability of an abnormal peristaltic sequence with each swallow was 1%, 38%, and 16% for sham, EGJ, and gastric band groups, respectively (P < 0.005, pairwise comparisons of band groups with sham). Conclusions: Nonadjustable gastric banding results in impaired esophageal body motility, a reduction in esophageal peristaltic pressure, and a reduction in resting lower esophageal sphincter pressure. These findings suggest that gastric banding causes esophageal outlet obstruction and subsequent decompensation of peristaltic function as well as a compromise of the native antireflux mechanism. C1 Portland VA Med Ctr, Surg Serv, Dept Surg, Portland, OR 97207 USA. Oregon Hlth & Sci Univ, Dept Surg, Portland, OR USA. RP Jobe, BA (reprint author), Portland VA Med Ctr, Surg Serv, Dept Surg, P3Surg,POB 1034, Portland, OR 97207 USA. EM jobeb@ohsu.edu OI Diggs, Brian/0000-0003-3586-3757 NR 42 TC 20 Z9 20 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-4932 J9 ANN SURG JI Ann. Surg. PD NOV PY 2006 VL 244 IS 5 BP 723 EP 733 DI 10.1097/01.sla.0000218082.12999.9a PG 11 WC Surgery SC Surgery GA 108ZS UT WOS:000242278300017 PM 17060765 ER PT J AU von Boehmer, H AF von Boehmer, H. TI Can studies of tolerance ever lead to therapy? SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article; Proceedings Paper CT 8th International Symposium on Advances in Targeted Therapies CY APR 05-09, 2006 CL Cambridge, MA ID REGULATORY T-CELLS; IN-VIVO; DENDRITIC CELLS; BONE-MARROW; ANTIGEN; SELF; TRANSPLANTATION; INDUCTION; PEPTIDE; VITRO AB Studies in murine models have suggested that regulatory T (Treg) cells can be generated by any antigen and such antigen specific Treg cells not only prevent but also reverse unwanted immunity. Another key finding of these experimental studies is that Treg cells could possibly be used therapeutically to ameliorate disease because of their ability to interfere with the execution of effector programmes of fully differentiated T effector cells. However, more work is needed before these findings can be safely translated into better targeted therapy and prevention of unwanted immune responses in clinical settings. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP von Boehmer, H (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM harald_von_Boehmer@dfci.harvard.edu NR 23 TC 2 Z9 2 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD NOV PY 2006 VL 65 SU 3 BP 41 EP 43 DI 10.1136/ard.2006.058396 PG 3 WC Rheumatology SC Rheumatology GA 094CB UT WOS:000241215800009 ER PT J AU Wright, CD Wain, JC AF Wright, Cameron D. Wain, John C. TI Acute presentation of thymoma with infarction or hemorrhage SO ANNALS OF THORACIC SURGERY LA English DT Article AB The presentation of thymomas is variable; most are asymptomatic and others present with local compression symptoms or a parathymic syndrome. Rarely thymomas present as an acute emergency with severe chest pain from either infarction or hemorrhage of the tumor. This rare presentation usually leads the clinician initially away from the diagnosis of thymoma. We present 4 patients who presented with infarction (3 patients) and hemorrhage (1 patient) who were initially believed to have a lymphoma. Preoperative biopsies were unrevealing. All had a complete resection and were in the early Masaoka stage. There have been no recurrences in follow-up. The astute clinician should be aware of this unusual presentation. The prognosis seems to be good in patients who present with infarction or hemorrhage. C1 Harvard Univ, Massachusetts Gen Hosp, Dept Surg, Gen Thorac Surg Unit,Med Sch, Boston, MA 02114 USA. RP Wright, CD (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Surg, Gen Thorac Surg Unit,Med Sch, Blake 1570, Boston, MA 02114 USA. EM wright.cameron@mgh.harvard.edu NR 8 TC 4 Z9 5 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 NOV PY 2006 VL 82 IS 5 BP 1901 EP 1904 DI 10.1016/j.athoracsur.2006.02.082 PG 5 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 098CC UT WOS:000241497600057 PM 17062275 ER PT J AU Yaghoubian, A de Virgilio, C AF Yaghoubian, Arezou de Virgilio, Christian TI Noniatrogenic aneurysm of the distal radial artery: A case report SO ANNALS OF VASCULAR SURGERY LA English DT Article AB Radial artery aneurysms are extremely rare. The majority are traumatic in origin and are iatrogenic pseudoaneurysms following arterial cannulation. We present an unusual case of an idiopathic isolated aneurysm of the most distal portion of the radial artery. Interestingly, upon performance of the Allen test, it was determined that the majority of blood flow to the hand was derived from the aneurysmal artery. Arteriography showed an occluded ulnar artery, a tortuous superficial palmar arch and absent deep palmar arch, and multiple small vessels that arose from the aneurysm that supplied the thumb. Given these findings, it was determined that there would be a significant risk of digital ischemia and gangrene if operative repair was attempted. A course of nonoperative management with observation was recommended. C1 Harbor UCLA Med Ctr, Dept Surg, Div Vasc Surg, Los Angeles, CA USA. W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. RP de Virgilio, C (reprint author), 1000 W Carson St,Bldg 1-E,Box 25 Torrance, Torrance, CA 90509 USA. EM cdevirgilio@labiomed.org NR 7 TC 8 Z9 11 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0890-5096 J9 ANN VASC SURG JI Ann. Vasc. Surg. PD NOV PY 2006 VL 20 IS 6 BP 784 EP 786 DI 10.1007/s10016-006-9121-0 PG 3 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 117CM UT WOS:000242850300014 PM 17103134 ER PT J AU Park, CH Robicsek, A Jacoby, GA Sahm, D Hooper, DC AF Park, Chi Hye Robicsek, Ari Jacoby, George A. Sahm, Daniel Hooper, David C. TI Prevalence in the United States of aac(6 ')-Ib-cr encoding a ciprofloxacin-modifying enzyme SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID MEDIATED QUINOLONE RESISTANCE; PLASMID; ENTEROBACTERIACEAE; MECHANISMS; GENE AB Among 313 Enterobacteriaceae from the United States with a ciprofloxacin MIC of >= 0.25 mu g/ml and reduced susceptibility to ceftazidime, aac(6')-Ib was present in 50.5% of isolates, and of these, 28% carried the cr variant responsible for low-level ciprofloxacin resistance. aac(6')-Ib-cr was geographically widespread, stable over time, most common in Escherichia coli, equally prevalent in ciprofloxacin-susceptible and -resistant strains, and not associated with qnr genes. C1 Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Evanston NW Healthcare, Evanston, IL USA. Lahey Clin Fdn, Burlington, MA USA. Focus BioInova, Herndon, VA USA. RP Hooper, DC (reprint author), Massachusetts Gen Hosp, Div Infect Dis, 55 Fruit St, Boston, MA 02114 USA. EM dhooper@partners.org FU NIAID NIH HHS [AI43312, AI57576, R01 AI043312, R01 AI057576] NR 13 TC 355 Z9 410 U1 4 U2 30 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 NOV PY 2006 VL 50 IS 11 BP 3953 EP 3955 DI 10.1128/AAC.00915-06 PG 3 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 104DC UT WOS:000241935200067 PM 16954321 ER PT J AU Joseph, DK Huppert, TJ Franceschini, MA Boas, DA AF Joseph, Danny K. Huppert, Theodore J. Franceschini, Maria Angela Boas, David A. TI Diffuse optical tomography system to image brain activation with improved spatial resolution and validation with functional magnetic resonance imaging SO APPLIED OPTICS LA English DT Article ID NEAR-INFRARED SPECTROSCOPY; SENSORY STIMULATION; LIMITATIONS; FMRI AB Although most current diffuse optical brain imaging systems use only nearest-neighbor measurement geometry, the spatial resolution and quantitative accuracy of the imaging can be improved through the collection of overlapping sets of measurements. A continuous-wave diffuse optical imaging system that combines frequency encoding with time-division multiplexing to facilitate overlapping measurements of brain activation is described. Phantom measurements to confirm the expected improvement in spatial resolution and quantitative accuracy are presented. Experimental results showing the application of this instrument for imaging human brain activation are also presented. The observed improvement in spatial resolution is confirmed by functional magnetic resonance imaging. (c) 2006 Optical Society of America. C1 Harvard Univ, Sch Med, Ctr Biomed Imaging, Dept Radiol,Massachusetts Gen Hosp, Charlestown, MA 02129 USA. RP Joseph, DK (reprint author), Harvard Univ, Sch Med, Ctr Biomed Imaging, Dept Radiol,Massachusetts Gen Hosp, Charlestown, MA 02129 USA. EM danny@nmr.mgh.harvard.edu FU NCRR NIH HHS [P41 RR14075]; NIBIB NIH HHS [R01 EB001954, R01 EB001954-06, R01-EB001954, R01-EB002482] NR 21 TC 78 Z9 80 U1 1 U2 5 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 NOV 1 PY 2006 VL 45 IS 31 BP 8142 EP 8151 DI 10.1364/AO.45.008142 PG 10 WC Optics SC Optics GA 099BO UT WOS:000241567700025 PM 17068557 ER PT J AU Williams, CM Bellucci, KSW Liu, V Levins, P AF Williams, Christy M. Bellucci, Kirsten S. W. Liu, Vincent Levins, Paul TI Erythematous papular rash on the upper back area - Caterpillar dermatitis, or erucism SO ARCHIVES OF DERMATOLOGY LA English DT Article ID AUTOMERIS-IO C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Williams, CM (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD NOV PY 2006 VL 142 IS 11 BP 1503 EP 1504 PG 2 WC Dermatology SC Dermatology GA 107GB UT WOS:000242157600018 ER PT J AU Andrade-Sierra, J Contreras, AM Monteon, FJ Celis, A Gutierrez, R Montanez, JL Ruelas, S Baid-Agrawal, S Chung, RT AF Andrade-Sierra, Jorge Contreras, Ana M. Monteon, Francisco J. Celis, Alfredo Gutierrez, Rodolfo Montanez, Jose L. Ruelas, Sara Baid-Agrawal, Seema Chung, Raymond T. CA Mexican Cooperative Grp TI Risk factors and incidence of posttransplant diabetes mellitus in Mexican kidney recipients SO ARCHIVES OF MEDICAL RESEARCH LA English DT Article DE incidence; posttransplant diabetes mellitus (PTDM); risk factors; kidney transplant ID RENAL-TRANSPLANT RECIPIENTS; DECREASED INSULIN-SECRETION; CYCLOSPORINE-A; HEPATITIS-C; ALLOGRAFT RECIPIENTS; TACROLIMUS; RESISTANCE; IMMUNOSUPPRESSION; HYPERGLYCEMIA; THERAPY AB Background. Many risk factors are associated with the development of posttransplant diabetes mellitus (PTDM), which has adverse effects on graft and patient survival. We report the incidence and risk factors associated with the development of PTDM in Mexican kidney recipients. Methods. In a retrospective cohort study, we included kidney transplants performed between January 1, 1994 and December 31, 2000; all patients were followed up for at least 1 year posttransplantation. PTDM was defined as fasting blood glucose > 126 mg/dL on at least two occasions. Statistical analysis included estimation of crude relative risk (RR) with 95% confidence intervals (CI). Adjusted RR and 95% Cl by logistic regression were used. Results. We studied 522 kidney recipients. Fifty three (10.1%) cases of PTDM were identified in this cohort. Cumulative dosage of prednisone (PDN) > 13 g (RR 7.6, 95% Cl 1.5-16.3 p <0.0001) and the presence of >= 1 acute rejection episodes (RR 3.7, 95% Cl 1.2-11.6 p < 0.001 were independent risk factors associated with the development of PTDM. Obesity (RR 2.6, 95% Cl 0.8-8.7, p = 0.083) and age range of 40-49 years (RR 2.0; 95% CI 0.6-7.2, p = 0.093) were identified as marginal risk factors. Conclusions. The incidence of PTDM in kidney recipients was 10.1% in our population. Cumulative PDN dosage and presence of >= 1 acute rejection episodes were independent risk factors for the development of PTDM. These results are consistent with prior studies of the diabetogenic effect of the PDN. The relationship between acute rejection and PTDM deserves further investigation in order to learn more about the role that inflammatory mechanisms may play in this association. (C) 2006 IMSS. Published by Elsevier Inc. C1 Mexican Inst Social Secur, Dept Nephrol, Guadalajara, Jalisco, Mexico. Mexican Inst Social Secur, Transplant Unit, Guadalajara, Jalisco, Mexico. Mexican Inst Social Secur, Clin Res Unit, Specialties Hosp, W Natl Med Ctr, Guadalajara, Jalisco, Mexico. Mexican Inst Social Secur, Dept Internal Med, Guadalajara, Jalisco, Mexico. Mexican Inst Social Secur, Mexican Cooperat Grp Study Hepat Kidney Dis, Guadalajara, Jalisco, Mexico. Univ Med Berlin, Dept Nephrol & Med Intens Care, Campus Virchow Klinikum, Charite, Berlin, Germany. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastroenterol Unit, Boston, MA USA. RP Contreras, AM (reprint author), Colonia Jardines Country, San Juan Ulua No 1633, Guadalajara, Jalisco, Mexico. EM acontreras53@hotmail.com NR 32 TC 6 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0188-4409 J9 ARCH MED RES JI Arch. Med. Res. PD NOV PY 2006 VL 37 IS 8 BP 961 EP 966 DI 10.1016/j.arcmed.2006.05.004 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 099TG UT WOS:000241618200006 PM 17045111 ER PT J AU Akomolafe, A Beiser, A Meigs, PB Au, R Green, RC Farrer, LA Wolf, PA Seshadri, S AF Akomolafe, Abimbola Beiser, Alexa Meigs, Phdjames B. Au, Rhoda Green, Robert C. Farrer, Lindsay A. Wolf, Philip A. Seshadri, Sudha TI Diabetes mellitus and risk of developing Alzheimer disease - Results from the Framingham study SO ARCHIVES OF NEUROLOGY LA English DT Article ID INSULIN-DEGRADING ENZYME; COGNITIVE IMPAIRMENT; VASCULAR DEMENTIA; OLDER WOMEN; APOE GENE; POPULATION; DECLINE; STROKE; HYPERINSULINEMIA; PERFORMANCE AB Background: Diabetes mellitus (DM) could increase the risk of Alzheimer disease (AD) through several biologically plausible pathways, but the relationship between DM and the development of AD remains uncertain. Objective: To compare the risk of developing AD in subjects with and without DM. Design: Prospective community-based cohort study. Participants: Framingham Study Original cohort participants who were dementia free and-attended the 16th biennial examination (n = 2210 persons, 1325 women; mean age, 70 years). Main Outcome Measures: Relative risk of incident AD (criteria from the National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association) associated with baseline DM (casual plasma glucose >= 200 mg/dL [>= 11.1 mmol/L] or use of insulin or a hypoglycemic drug) in overall group and within subgroups defined by apolipoprotein E genotype and plasma homocysteine levels; models were adjusted for age, sex, and cardiovascular risk factors. Results: At baseline, 202 participants (9.1%) had DM During the follow-up period (mean, 12.7 years; range, 1-20 years), 17 of 202 persons with DM (8.4%) and 220 of 2008 persons without DM (11.0%) developed AD, yielding a relative risk of 1.15 (95% confidence interval, 0.65-2.05). Among subjects without an apolipoprotein E F,4 allele or elevated plasma homocysteine levels, 44 of 684 persons (6.4%) developed AD; relative risk for AD comparing diabetic patients with nondiabetic patients was 2.98 (95% confidence interval, 1.06-8.39; P = .03). The effect was strongest in persons aged 75 years or older with a relative risk of 4.77 (95% confidence interval, 1.28-17.72; P = .02). Conclusion: Diabetes mellitus did not increase the risk of incident AD in the Framingham cohort overall; however, DM may be a risk factor for AD in the absence of other known major AD risk factors. C1 Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. Boston Univ, Sch Publ Hlth, Dept Med, Genet Program, Boston, MA 02118 USA. Morehouse Sch Med, Dept Med, Atlanta, GA 30310 USA. Massachusetts Gen Hosp, Div Gen Med, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. NHLBI, Framingham Heart Study, Framingham, MA USA. RP Seshadri, S (reprint author), Boston Univ, Sch Med, Dept Neurol, 715 Albany St,B-608, Boston, MA 02118 USA. EM suseshad@bu.edu OI Farrer, Lindsay/0000-0001-5533-4225 FU NHLBI NIH HHS [N01-HC-25195]; NIA NIH HHS [3R01-AG09029, 5R01-AG08122, 5R01-AG16495, P30 AG13846]; NINDS NIH HHS [5R01-NS17950] NR 42 TC 146 Z9 151 U1 6 U2 20 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD NOV PY 2006 VL 63 IS 11 BP 1551 EP 1555 DI 10.1001/archneur.63.11.1551 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 104JJ UT WOS:000241954400005 PM 17101823 ER PT J AU Menke, MN Feke, GT McMeel, JW Branagan, A Hunter, Z Treon, SP AF Menke, Marcel N. Feke, Gilbert T. McMeel, J. Wallace Branagan, Andrew Hunter, Zachary Treon, Steven P. TI Hyperviscosity-related retinopathy in Waldenstrom macroglobulinemia SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID MANAGEMENT AB Objectives: To determine the earliest retinal changes associated with Waldenstrom macroglobulinemia (WM) and to ascertain the serum IgM and serum viscosity (SV) levels at which these changes occur. Methods: Patients with WM were evaluated using indirect ophthalmoscopy with scleral depression, laser Doppler retinal blood flow measurements, and serum IgM and SV determinations. Hemodynamic findings were compared with those of a group of age-matched controls. A retinopathy severity scale was developed, and the associated IgM and SV values were related to particular morphologic changes. Results: A total of 46 patients with WM and 14 age-matched, healthy controls participated in the study. Patients exhibited far-peripheral hemorrhages and venous dilation with increasing SV and IgM values. Central retinal changes were associated with significantly higher SV values. Retinal vessel diameter increased with increasing serum IgM and SV levels. The mean IgM level of patients with the earliest retinal changes was 5442 mg/dL. The mean SV level was 3.1 cP. Conclusions: Retinal manifestations of hyperviscosity syndrome occur at lower serum IgM and SV levels than previously reported. Indirect ophthalmoscopy with scleral depression along with retinal vessel diameter measurements are able to detect the earliest hyperviscosity syndrome-related complications and should be considered in the treatment of patients with WM. C1 Schepens Retina Associates Fdn, Boston, MA 02215 USA. Dana Farber Canc Inst, Bing Program Waldenstroms Macroglobulinemia, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Ophthalmol, Dept Surg, Boston, MA USA. Harvard Univ, Sch Med, Div Ophthalmol, Dept Ophthalmol, Boston, MA USA. Harvard Univ, Sch Med, Div Ophthalmol, Dept Med, Boston, MA USA. RP Feke, GT (reprint author), Schepens Retina Associates Fdn, 1 Autumn St,6th Floor, Boston, MA 02215 USA. EM feke@schepens.com RI Hunter, Zachary/H-3018-2013 OI Hunter, Zachary/0000-0002-1689-1691 NR 17 TC 33 Z9 35 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD NOV PY 2006 VL 124 IS 11 BP 1601 EP 1606 DI 10.1001/archopht.124.11.1601 PG 6 WC Ophthalmology SC Ophthalmology GA 104VG UT WOS:000241987700011 PM 17102008 ER PT J AU Warden, SM Pachydaki, SI Christoforidis, JB D'Amico, DJ Loewenstein, JI AF Warden, Scott M. Pachydaki, Sophia I. Christoforidis, John B. D'Amico, Donald J. Loewenstein, John I. TI Choroidal neovascularization after epiretinal membrane removal SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID SURGERY C1 Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. RP Loewenstein, JI (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM jloewenste@meei.harvard.edu NR 5 TC 2 Z9 2 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD NOV PY 2006 VL 124 IS 11 BP 1652 EP 1654 DI 10.1001/archopht.124.11.1652 PG 4 WC Ophthalmology SC Ophthalmology GA 104VG UT WOS:000241987700020 PM 17102017 ER PT J AU Weinand, C Peretti, GM Adams, SB Randolph, MA Savvidis, E Gill, TJ AF Weinand, Christian Peretti, Giuseppe M. Adams, Samuel B., Jr. Randolph, Mark A. Savvidis, Estafios Gill, Thomas J. TI Healing potential of transplanted allogeneic chondrocytes of three different sources in lesions of the avascular zone of the meniscus: a pilot study SO ARCHIVES OF ORTHOPAEDIC AND TRAUMA SURGERY LA English DT Article DE meniscus; repair; implant; allogeneic; chondrocytes; tissue engineering; large animal study ID CLASS-II; ARTICULAR CHONDROCYTES; CELL-FUNCTION; EXPRESSION; ICAM-1 AB Successful treatment of tears to the avascular region of the meniscus remains a challenge. Current repair techniques, such as sutures and anchors, are effective in stabilizing the peripheral, vascularized regions of the meniscus, but are not adequate for promoting healing in the avascular region. The purpose of this study was to demonstrate the healing ability of a tissue-engineered repair technique using allogenic chondrocytes from three different sources for the avascular zone of the meniscus. Material and methods: Articular, auricular, and costal chondrocytes were harvested from 3-month-old Yorkshire swine. A 1-cm bucket-handle lesion was created in the avascular zone of each three swine. A cell-scaffold construct, composed of a single chondrocyte cell type and Vicryl mesh, was implanted into the lesion and secured with two vertical mattress sutures. Controls consisted of each three sutured unseeded mesh implants, suture only, and untreated lesions. The swine were allowed immediate post-operative full weight bearing. Menisci and controls were harvested after 12 weeks. Results: In all experimental samples, lesion closure was observed. Gross mechanical testing with two Adson forceps demonstrated bonding of the lesion. Histological analysis showed formation of new tissue in all three experimental samples. None of the control samples demonstrated closure and formation of new matrix. Conclusion: We present preliminary data that demonstrates the potential of a tissue-engineered, allogenic cellular repair to provide successful healing of lesions in the avascular zone in a large animal model. C1 Massachusetts Gen Hosp, Lab Musculoskeletal Tissue Engn, Dept Orthopaed Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Lab Musculoskeletal Tissue Engn, Dept Plast Surg, Boston, MA 02114 USA. Vogtlandklinikum Plauen, Abt Orthopad, D-08529 Plauen, Germany. RP Weinand, C (reprint author), Massachusetts Gen Hosp, Lab Musculoskeletal Tissue Engn, Dept Orthopaed Surg, WACC 453,15 Parkman St, Boston, MA 02114 USA. EM chwscot@yahoo.com RI Peretti, Giuseppe/K-6358-2016 OI Peretti, Giuseppe/0000-0001-9341-7187 NR 18 TC 24 Z9 27 U1 1 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0936-8051 J9 ARCH ORTHOP TRAUM SU JI Arch. Orthop. Trauma Surg. PD NOV PY 2006 VL 126 IS 9 BP 599 EP 605 DI 10.1007/s00402-005-0100-7 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 092NY UT WOS:000241105600005 PM 16411123 ER PT J AU Pommier, P Liebsch, NJ Deschler, DG Lin, DT McIntyre, JF Barker, FG Adams, JA Lopes, VV Varvares, M Loeffler, JS Chan, AW AF Pommier, Pascal Liebsch, Nobert J. Deschler, Daniel G. Lin, Derrick T. McIntyre, James F. Barker, Fred G., II Adams, Judy A. Lopes, Vrishali V. Varvares, Mark Loeffler, Jay S. Chan, Annie W. TI Proton beam radiation therapy for skull base adenoid cystic carcinoma SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article; Proceedings Paper CT 17th Annual Meeting of the North-America-Skull-Base-Society CY FEB 16-19, 2006 CL Phoenix, AZ SP N Amer Skull Base Soc ID SALIVARY-GLAND TUMORS; PARANASAL SINUS CANCER; NEUTRON RADIOTHERAPY; PHOTON IRRADIATION; SURGERY; HEAD; NECK; EXPERIENCE; RISK AB Objective: To determine the treatment outcome and prognostic factors in patients with adenoid cystic carcinoma of the skull base treated with proton beam radiation therapy. Design: Retrospective analysis. Setting: Massachusetts General Hospital, Massachusetts Eye and Ear Infirmary, and Harvard Medical School, Boston. Patients: From 1991 to 2002, 23 patients with newly diagnosed adenoid cystic carcinoma with skull base extension were treated with combined proton and photon radiotherapy. There was tumor involvement of the sphenoid sinus in 61% of patients (14), nasopharynx in 61% (14), clivus in 48% (11), and cavernous sinus in 74% (17). The extent of surgery was biopsy alone in 48% (11), partial resection in 39% (9), and gross total resection with positive margins in 13% (3). The median total dose to the primary site was 75.9 cobalt-gray equivalent. The median follow-up of all surviving patients was 64 months. Main Outcome Measures: Locoregional control and disease-free survival and overall survival rates. Results: Tumors recurred locally in 2 patients at 33 and 68 months, respectively. No patients developed neck recurrence. Eight patients had distant metastasis as the first site of recurrence. The local control rate at 5 years was 93%. The rate of freedom from distant metastasis at 5 years was 62%. The disease-free and overall survival rates at 5 years were 56% and 77%, respectively. In multivariate analysis, significant adverse factors predictive for overall survival were change in vision at presentation (P=.02) and involvement of sphenoid sinus and clivus (P=.01). Conclusions: High-dose conformal proton beam radiation therapy results in a very encouraging local control rate in patients with adenoid cystic carcinoma of the skull base. Changes in vision at presentation and tumor involvement of the sphenoid sinus and clivus are important prognostic factors. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Chan, AW (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 55 Fruit St,Cox 3, Boston, MA 02114 USA. EM awchan@partners.org NR 28 TC 86 Z9 87 U1 0 U2 8 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD NOV PY 2006 VL 132 IS 11 BP 1242 EP 1249 DI 10.1001/archotol.132.11.1242 PG 8 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 103WR UT WOS:000241918400013 PM 17116822 ER PT J AU Smogorzewska, A Brandt, JT Chandler, WL Cunningham, MT Hayes, TE Olson, JD Kottke-Marchant, K Van Cott, EM AF Smogorzewska, Agata Brandt, John T. Chandler, Wayne L. Cunningham, Mark T. Hayes, Timothy E. Olson, John D. Kottke-Marchant, Kandice Van Cott, Elizabeth M. TI Effect of fondaparinux on coagulation assays - Results of College of American Pathologists proficiency testing SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID HEPARIN-ASSOCIATED THROMBOCYTOPENIA; HIP-REPLACEMENT SURGERY; VENOUS THROMBOEMBOLISM; POSTOPERATIVE FONDAPARINUX; UNFRACTIONATED HEPARIN; PLATELET ACTIVATION; INITIAL TREATMENT; ENOXAPARIN; PENTASACCHARIDE; PREVENTION AB Context-Fondaparinux, a factor Xa inhibitor, is approved for thromboprophylaxis after orthopedic surgery and for treatment of venous thromboembolism. It may also be efficacious, safe, and cost-effective for other patients; thus, more widespread use of fondaparinux is likely. The effect of fondaparinux on coagulation testing needs to be thoroughly examined. Objective.-To report the effects of fondaparinux on coagulation tests (prothrombin time, activated partial thromboplastin time, fibrinogen, antithrombin, factor VIII, thrombin time, anti-factor Xa) across diverse methodologies. Design.-Samples with different concentrations of fondaparinux (0, 0.4, 0.8, and 2.0 mu g/mL) were sent to laboratories participating in the College of American Pathologists Comprehensive Coagulation proficiency survey (N = 898). Laboratory-specific methods were used to assay coagulation parameters. Results.-Prophylactic or therapeutic fondaparinux prolonged the prothrombin time by approximately I second and the activated partial thromboplastin time by 4 to 5 seconds, and reduced factor VIII from 119% to 107% and 102%, respectively. Supratherapeutic fondaparinux reduced factor VIII to 85%. The activated partial thromboplastin time was prolonged in 19%, 29%, and 52% of laboratories with prophylactic, therapeutic, and supratherapeutic fondaparinux levels, respectively. Fibrinogen, antithrombin, and thrombin time assays did not show clinically significant changes. When measuring fondaparinux concentration using an anti-factor Xa assay, the most accurate results were obtained when fondaparinux was used as the calibrator. Conclusions.-Fondaparinux, even in prophylactic doses, slightly prolongs the prothrombin time and activated partial thromboplastin time and can interfere with factor VIII assays, but it has no clinically relevant effect on fibrinogen, antithrombin, or thrombin time. A fondaparinux standard curve should be used for reporting fondaparinux levels using an anti-factor Xa assay. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol & Lab Med, Boston, MA 02115 USA. Eli Lilly & Co, Indianapolis, IN 46285 USA. Univ Washington, Harborview Med Ctr, Dept Lab Med, Seattle, WA 98195 USA. Univ Kansas, Med Ctr, Dept Pathol, Kansas City, MO USA. Maine Med Ctr, Dept Pathol, Portland, ME 04102 USA. Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78285 USA. Cleveland Clin Fdn, Dept Clin Pathol, Cleveland, OH 44195 USA. RP Van Cott, EM (reprint author), Massachusetts Gen Hosp, Div Lab Med, Gray Jackson 235,55 Fruit St, Boston, MA 02114 USA. RI Smogorzewska, Agata/B-8891-2011 NR 23 TC 26 Z9 26 U1 0 U2 2 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD NOV PY 2006 VL 130 IS 11 BP 1605 EP 1611 PG 7 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 100ZQ UT WOS:000241709100006 PM 17076521 ER PT J AU Renshaw, AA Haja, JC Neal, MH Wilbur, DC AF Renshaw, Andrew A. Haja, Jennifer C. Neal, Margaret H. Wilbur, David C. CA Cytopathology Res Comm TI Distinguishing carcinoid tumor of the mediastinum from thymoma - Correlating cytologic features and performance in the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytopathology SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID NEEDLE ASPIRATION CYTOLOGY; SMALL-CELL CARCINOMA; NEUROENDOCRINE CARCINOMAS; THYMUS; BIOPSY; LUNG; DIAGNOSIS AB Context.-The cytologic features of carcinoid tumor in mediastinal fine-needle aspiration are well described. Nevertheless, this tumor may be difficult to distinguish from thymoma in this site. Objective.-We sought to correlate the cytologic features of carcinoid tumor of the mediastinum in the College of American Pathologists Interlaboratory Comparison Program in Nongynecologic Cytopathology with the frequency of misclassification as thymoma. Design.-We reviewed 446 interpretations from 18 different cases of carcinoid tumor in mediastinum and correlated the cytologic features with performance. Results.-Cases were more frequently classified as thymoma (158 responses, 35%) than as carcinoid tumor (126 responses, 28%). The best-performing case was classified as carcinoid tumor only 56% of the time. Three cytologic patterns were identified. Four cases consisted of isolated round cells with salt-and-pepper chromatin. Four cases consisted of isolated spindle and round cells with salt-and-pepper chromatin. The remaining 10 cases consisted of cohesive fragments of crowded cells with finely granular chromatin showing numerous pyknotic cells mimicking lymphocytes. Prominent vasculature patterns were not a feature of any of the cases. There was no correlation between any pattern and the rate of classification as carcinoid tumor or thymoma (P > .05). Conclusions.-Carcinoid tumor of the mediastinum is frequently misclassified as thymoma in this program. Al though some cytologic patterns resemble thymoma, the lack of correlation of these patterns with performance suggests that at least part of the reason for misclassification may be failure to consider the correct diagnosis or a lack of familiarity with discriminating cytologic criteria. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Baptist Hosp Miami, Dept Pathol, Miami, FL USA. Coll Amer Pathologists, Northfield, IL USA. KWB Pathol Associates, Dept Pathol, Tallahassee, FL USA. RP Wilbur, DC (reprint author), Massachusetts Gen Hosp, Dept Pathol, 55 Fruit St,Warren 120, Boston, MA 02114 USA. EM dwilbur@partners.org NR 22 TC 4 Z9 4 U1 0 U2 0 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD NOV PY 2006 VL 130 IS 11 BP 1612 EP 1615 PG 4 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 100ZQ UT WOS:000241709100007 PM 17076522 ER PT J AU Rubin, BP Fletcher, CDM Inwards, C Montag, AG Peabody, T Qualman, SJ Rosenberg, AE Weiss, S Krausz, T AF Rubin, Brian P. Fletcher, Christopher D. M. Inwards, Carrie Montag, Anthony G. Peabody, Terrance Qualman, Stephen J. Rosenberg, Andrew E. Weiss, Sharon Krausz, Thomas TI Protocol for the examination of specimens from patients with soft tissue tumors of intermediate malignant potential, malignant soft tissue tumors, and benign/locally aggressive and malignant bone tumors SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID PROGNOSTIC-FACTOR; EWINGS-SARCOMA; ADULT PATIENTS; CHEMOTHERAPY; CLASSIFICATION; OSTEOSARCOMA; NECROSIS C1 Univ Washington, Med Ctr, Seattle, WA 98195 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Mayo Clin, Rochester, MN USA. Univ Chicago, Dept Pathol, Chicago, IL 60637 USA. Childrens Hosp, Dept Lab Med, Columbus, OH 43205 USA. Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Boston, MA 02114 USA. Emory Univ, Atlanta, GA 30322 USA. RP Rubin, BP (reprint author), Univ Washington, Med Ctr, 1959 NE Pacific St,Box 356100, Seattle, WA 98195 USA. EM bprubin@u.washington.edu NR 18 TC 23 Z9 24 U1 1 U2 1 PU COLLEGE AMER PATHOLOGISTS PI NORTHFIELD PA C/O KIMBERLY GACKI, 325 WAUKEGAN RD, NORTHFIELD, IL 60093-2750 USA SN 0003-9985 J9 ARCH PATHOL LAB MED JI Arch. Pathol. Lab. Med. PD NOV PY 2006 VL 130 IS 11 BP 1616 EP 1629 PG 14 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 100ZQ UT WOS:000241709100008 PM 17076523 ER PT J AU Elosua, R Cupples, LA Fox, CS Polak, JF D'Agostino, RA Wolf, PA O'Donnell, CJ Ordovas, JM AF Elosua, Roberto Cupples, L. Adrienne Fox, Caroline S. Polak, Joseph F. D'Agostino, Ralph A., Sr. Wolf, Philip A. O'Donnell, Christopher J. Ordovas, Jose M. TI Association between well-characterized lipoprotein-related genetic variants and carotid intimal medial thickness and stenosis: The Framingham Heart Study SO ATHEROSCLEROSIS LA English DT Article DE carotid; epidemiology; genetics; lipids ID CHOLESTEROL LEVELS; LIPASE GENE; MYOCARDIAL-INFARCTION; PLASMA-LIPIDS; DISEASE RISK; POLYMORPHISM; PROTEIN; ATHEROSCLEROSIS; STROKE; MEN AB Objective: To determine the association of well-characterized lipoprotein-related genetic variants with carotid intimal medial thickness (IMT) and stenosis. Methods: 3380 men and women from the Framingham Offspring Study underwent carotid ultrasound to determine carotid IMT and stenosis >= 25%. We genotyped 12 variants in 10 lipoprotein-related genes known to be associated with significant differences in lipoprotein levels. Results: For most of the variants, there was no association with carotid IMT. In multivariable, sex-specific analyses, the rare allele of the cholesterol ester transfer protein (CETP) TaqIB variant was associated with lower ICA IMT in men. Hypertension was associated with higher ICA IMT only in male carriers of the rare allele of the APOCIII Sst-1 variant (p for the interaction=0.041). In analyses of carotid stenosis in male, carriers of the lipoprotein lipase (LPL) N291S rare variant showed a higher risk of carotid stenosis (OR = 2.59, 95% confidence interval: 1.11-6.02, p=0.028) compared to NN genotype. Conclusions: While there is no evidence for a significant association of several common lipoprotein-related genetic variants with carotid IMT, our results are consistent with the previously reported role of CETP and LPL genetic variants in cardiovascular risk and the possible modulation of the association between hypertension and carotid IMT by APOCIII Sst-1 variant. (c) 2005 Elsevier Ireland Ltd. All rights reserved. C1 NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Prevent Med & Epidemiol, Boston, MA 02118 USA. Boston Univ, Dept Biostat, Boston, MA 02215 USA. Tufts Univ, USDA, Human Nutr Res Ctr Aging, Medford, MA 02155 USA. Inst Municipal Invest Med, E-08003 Barcelona, Spain. NHLBI, NIH, Bethesda, MD 20892 USA. RP O'Donnell, CJ (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave Suite 2, Framingham, MA 01702 USA. EM codonnell@nih.gov OI Cupples, L. Adrienne/0000-0003-0273-7965; ELOSUA, ROBERTO/0000-0001-8235-0095; Ordovas, Jose/0000-0002-7581-5680 FU NHLBI NIH HHS [N01-HC-25195, HL54776]; NINDS NIH HHS [5R01-NS17950-22] NR 27 TC 16 Z9 16 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 NOV PY 2006 VL 189 IS 1 BP 222 EP 228 DI 10.1016/j.atherosclerosis.2005.12.005 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 097SD UT WOS:000241467900028 PM 16430904 ER PT J AU Dick, SE Werth, VP AF Dick, Sarah E. Werth, Victoria P. TI Pemphigus: A treatment update SO AUTOIMMUNITY LA English DT Article DE pemphigus; bullous disease; systemic corticosteroid; medication ID CYCLOPHOSPHAMIDE PULSE THERAPY; NECROSIS-FACTOR-ALPHA; TERM FOLLOW-UP; ANTI-CD20 MONOCLONAL-ANTIBODY; GLUCOCORTICOID-SPARING AGENT; MYCOPHENOLATE-MOFETIL; ENDEMIC PEMPHIGUS; ADJUVANT THERAPY; CHOLINERGIC-RECEPTORS; INITIAL TREATMENT AB Pemphigus is a group of rare autoimmune mucocutaneous bullous diseases with potential significant morbidity and mortality. The two main subtypes are pemphigus vulgaris (PV) and pemphigus foliaceus (PF). Systemic corticosteroid use and other advances in management have dramatically decreased the mortality rate for pemphigus. At present, the primary cause of morbidity and mortality is complications from treatment. Thus, the goal of pemphigus management is to induce and maintain remission with the lowest possible doses of medication and with the fewest side effects. Although our controlled studies to evaluate the true effectiveness of the available therapies. Here we review the available treatment options and novel therapies for pemphigus and the supporting data. C1 Univ Penn, Philadelphia VA Med Ctr, Dept Dermatol, Philadelphia, PA 19104 USA. RP Werth, VP (reprint author), Univ Penn, Philadelphia VA Med Ctr, Dept Dermatol, 2 Rhoads Pavil,36th & Spruce, Philadelphia, PA 19104 USA. EM werth@mail.med.upenn.edu FU NIAMS NIH HHS [K24-AR 02207] NR 96 TC 14 Z9 18 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0891-6934 J9 AUTOIMMUNITY JI Autoimmunity PD NOV PY 2006 VL 39 IS 7 BP 591 EP 599 DI 10.1080/08916930600972008 PG 9 WC Immunology SC Immunology GA 106MG UT WOS:000242104100008 PM 17101503 ER PT J AU Waldman, ID Gizer, IR Fagerness, JA McGrath, CL Rowe, DC AF Waldman, Irwin D. Gizer, Ian R. Fagerness, Jesen A. McGrath, Casey L. Rowe, David C. TI Is COMT a risk factor for ADHD? Testing for association with multiple markers in a gene-based framework SO BEHAVIOR GENETICS LA English DT Meeting Abstract CT 36th Annual Meeting of the Behavior-Genetics-Association CY JUN 24, 2006 CL Storrs, CT SP Behav Genet Assoc C1 Emory Univ, Atlanta, GA 30322 USA. Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. Univ Arizona, Late Program Genet & Cell Biol, Tucson, AZ USA. EM psyiw@emory.edu RI McGrath, Casey/B-6826-2008 NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0001-8244 J9 BEHAV GENET JI Behav. Genet. PD NOV PY 2006 VL 36 IS 6 BP 986 EP 987 PG 2 WC Behavioral Sciences; Genetics & Heredity; Psychology, Multidisciplinary SC Behavioral Sciences; Genetics & Heredity; Psychology GA 092WR UT WOS:000241128600088 ER PT J AU Paik, JH AF Paik, J-H TI FOXOs in the maintenance of vascular homoeostasis SO BIOCHEMICAL SOCIETY TRANSACTIONS LA English DT Article DE Akt; angiogenesis; forkhead box O (FOXO); homoeostasis; phosphoinositide 3-kinase (PI3K); vascular cell type ID FORKHEAD TRANSCRIPTION FACTOR; PROTEIN-KINASE-B; FACTOR AFX; CELL-PROLIFERATION; FACTOR FKHR; OXIDATIVE STRESS; DOWN-REGULATION; INHIBITION; GENE; AKT AB The mammalian Fox0 (forkhead box 0) transcription factors Fox01, Fox03 and Fox04 represent one of several effector arms of the PI3K (phosphoinositide 3-kinase)-Akt signalling network that has been linked to cancer, metabolism and aging. Specific roles of the Fox0s in the vascular cell types have been investigated to reveal that they play redundant yet critical roles in the proliferation and survival of US (endothelial cells). Somatic deletions of all Fox0s engendered progressive, widespread and highly penetrant haemangiomas associated with altered proliferative/survival dynamics of ECs in our genetic model. Related work by Akt-Fox0 manipulation reported differentially regulated genes in ECs that may represent novel Fox0 targets, controlling EC growth and morphogenesis and mediating many of the consequences of Fox0 inactivation in the endothelium. Further studies on the action of these surrogate genes may provide important new insights into how the PI3K-Akt-Fox0 pathway could be exploited clinically to treat vascular disease's and lead to the invention of novel therapeutic approaches. Here recent studies elucidating the role of Fox0s in the maintenance of vascular homoeostasis and supporting that the mammalian Fox0 family serves essential roles in the maintenance of vascular stability and the suppression of aberrant vascular outgrowth are discussed. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Paik, JH (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM jihye_Paik@dfci.harvard.edu NR 51 TC 21 Z9 24 U1 0 U2 2 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0300-5127 J9 BIOCHEM SOC T JI Biochem. Soc. Trans. PD NOV PY 2006 VL 34 BP 731 EP 734 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 109EE UT WOS:000242289900018 PM 17052184 ER PT J AU DiBernardo, AB Cudkowicz, ME AF DiBernardo, Allitia B. Cudkowicz, Merit E. TI Translating preclinical insights into effective human trials in ALS SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE LA English DT Review DE amyotrophic lateral sclerosis; clinical trial; preclinical model; drug evaluation ID AMYOTROPHIC-LATERAL-SCLEROSIS; MOTOR-NEURON DISEASE; TRANSGENIC MOUSE MODEL; CU/ZN-SUPEROXIDE-DISMUTASE; GLIAL GLUTAMATE TRANSPORTER; INCREASED OXIDATIVE DAMAGE; NEUROFILAMENT HEAVY GENE; PLACEBO-CONTROLLED TRIAL; CELL-CULTURE MODEL; SUBUNIT-NF-L AB Amyotrophic lateral sclerosis (ALS) is a rapidly progressive, adult-onset neurodegenerative disease characterized by selective dysfunction and death of motor neurons in the brain and spinal cord. The disease is typically fatal within 3-5 years of symptom onset. There is no known cure and only riluzole, which was approved by the FDA in 1996 for treatment of ALS, has shown some efficacy in humans. Preclinical insights from model systems continue to furnish ample therapeutic targets, however, translation into effective therapies for humans remains challenging. We present an overview of clinical trial methodology for ALS, including a summary rationale for target selection and challenges to ALS clinical research. (c) 2006 Elsevier B.V. All rights reserved. C1 Massachusetts Gen Hosp, Neurol Clin Trials Unit, Dept Neurol, Charlestown, MA 02129 USA. RP DiBernardo, AB (reprint author), Massachusetts Gen Hosp, Neurol Clin Trials Unit, Dept Neurol, Bldg 149,13th St,Room 2271, Charlestown, MA 02129 USA. EM adibernardo@partners.org NR 128 TC 30 Z9 31 U1 1 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4439 J9 BBA-MOL BASIS DIS JI Biochim. Biophys. Acta-Mol. Basis Dis. PD NOV-DEC PY 2006 VL 1762 IS 11-12 BP 1139 EP 1149 DI 10.1016/j.bbadis.2006.03.007 PG 11 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 118FB UT WOS:000242926600016 PM 16713196 ER PT J AU Belogrudov, GI Schirf, V Demeler, B AF Belogrudov, Grogory I. Schirf, Virgil Demeler, Borries TI Reversible self-association of recombinant bovine factor B SO BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS LA English DT Article DE factor B; energy coupling; proton leak; cross-link; dimer; trimer; self-association; analytical ultracentrifugation; sedimentation equilibrium; sedimentation velocity; ultrascan ID MITOCHONDRIAL ATP SYNTHASE; CONSERVED GXXXG MOTIF; OXIDATIVE-PHOSPHORYLATION; SUBUNIT-G; F1F0-ATP SYNTHASE; PROTEIN; INHIBITOR; COMPLEX; CRISTAE; IDENTIFICATION AB The recombinant bovine factor B, obtained by a newly developed bacterial expression system, was found to exhibit features characteristic of a reversible self-associating system. Using size-sieving chromatography, distribution of the factor B species ranged from a monomer to a trimer, but not oligomers of higher molecular weights. At high protein concentrations, factor B migrated as a single band in a native gel. Cross-linking with the amino-reactive cross-linking reagent bis (sulfosuccinimidyl) suberate (BS), at a low cross-linker to protein ratio yielded cross-linked products identified as factor B dimer and trimer. The cross-linking pattern was shown to be a function of the protein and cross-linker concentrations. The range of sedimentation coefficients in a sedimentation velocity experiment suggested that the largest particle present in the distribution was more than twice as large as the smallest. The data obtained under multiple conditions in the sedimentation equilibrium experiments are best fit to a model describing a reversible self-association of a monomer-trimer of factor B species, with a dissociation constant Kd(1,3)=2.48 X 10(0-10) M-2. (c) 2006 Elsevier B.V. All rights reserved. C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol, Los Angeles, CA 90073 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. Univ Texas, Hlth Sci Ctr, Dept Biochem, San Antonio, TX 78229 USA. RP Belogrudov, GI (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol, Los Angeles, CA 90073 USA. EM gbelo@ucla.edu; demeler@biochem.uthscsa.edu FU NIGMS NIH HHS [R01 GM066085] NR 38 TC 7 Z9 7 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-9639 J9 BBA-PROTEINS PROTEOM JI BBA-Proteins Proteomics PD NOV PY 2006 VL 1764 IS 11 BP 1741 EP 1749 DI 10.1016/j.bbapap.2006.09.005 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 112UZ UT WOS:000242554300009 PM 17049939 ER PT J AU Tsiftsoglou, SA Arnold, JN Roversi, P Crispin, MD Radcliffe, C Lea, SM Dwek, RA Rudd, PM Sim, RB AF Tsiftsoglou, Stefanos A. Arnold, James N. Roversi, Pietro Crispin, Max D. Radcliffe, Catherine Lea, Susan M. Dwek, Raymond A. Rudd, Pauline M. Sim, Robert B. TI Human complement factor I glycosylation: Structural and functional characterisation of the N-linked oligosaccharides SO BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS LA English DT Article DE human; complement; factor I; serine protease; N-glycosylation; sialylation ID PERFORMANCE LIQUID-CHROMATOGRAPHY; C4B-BINDING PROTEIN; C4-BINDING PROTEIN; HUMAN-ERYTHROCYTE; C3B INACTIVATOR; RECEPTOR CR-1; FACTOR-H; SYSTEM; CELLS; IDENTIFICATION AB Factor I (fI) is a key serine protease that modulates the complement cascade by regulating the levels of C3 convertases. Human fI circulates in plasma as a heavily N-glycosylated (25-27% w/w) heterodimer composed of two disulphide linked chains, each carrying three N-linked oligosaccharide chains. It had been suggested that the oligosaccharides may have both structural and functional roles in the interactions with the natural substrate and the collactor during a catalysis. The N-linked glycans of each fI chain were characterised in detail and the analysis revealed a similar composition of the glycan pools with both chains heavily sialylated. Disialylated structures were in excess over monosialylated ones: 55% over 40% for the heavy chain and 62% over 35% for the light chain. The dominant type of glycan identified on both chains was A(2)G(2)S(2), a biantennary structure with chains terminating in sialic acid linked to galactose. The glycan characterisation facilitated a strategy for the partial deglycosylation of the enzyme. Assessment of the proteolytic activities of the native and partially deglycosylated forms of fI showed that both forms of the enzyme have very similar proteolytic activities against C3(NH3) indicating that the charged glycans of fI do not influence the fI-cofactor-substrate interactions. (c) 2006 Elsevier B.V. All rights reserved. C1 Univ Oxford, Dept Biochem, MRC, Immunochem Unit, Oxford OX1 3QU, England. Univ Oxford, Dept Biochem, Oxford Glycobiol Inst, Oxford OX1 3QU, England. Univ Oxford, Dept Biochem, Lab Mol Biophys, Oxford OX1 3QU, England. RP Tsiftsoglou, SA (reprint author), Harvard Univ, Sch Med, CBR Inst Biomed Res, 800 Huntington Ave, Boston, MA 02115 USA. EM tsiftsoglou@cbr.med.harvard.edu RI Roversi, Pietro/F-8925-2011; Lea, Susan/B-7678-2009; Sim, Robert/A-1354-2008 OI Roversi, Pietro/0000-0001-9280-9437; Lea, Susan/0000-0001-9287-8053; Sim, Robert/0000-0002-2855-7455 NR 49 TC 18 Z9 19 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-9639 J9 BBA-PROTEINS PROTEOM JI BBA-Proteins Proteomics PD NOV PY 2006 VL 1764 IS 11 BP 1757 EP 1766 DI 10.1016/j.bbapap.2006.09.007 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 112UZ UT WOS:000242554300011 PM 17055788 ER PT J AU Rajicic, N Finkelstein, DM Schoenfeld, DA AF Rajicic, Natasa Finkelstein, Dianne M. Schoenfeld, David A. CA Inflam Response Injury Resch TI Survival analysis of longitudinal microarrays SO BIOINFORMATICS LA English DT Article ID GENE-EXPRESSION DATA; B-CELL LYMPHOMA; BREAST-CANCER; MODEL; REGRESSION; DISCOVERY; ERROR AB Motivation: The development of methods for linking gene expressions to various clinical and phenotypic characteristics is an active area of genomic research. Scientists hope that such analysis may, for example, describe relationships between gene function and clinical events such as death or recovery. Methods are available for relating gene expression to measurements that are categorized or continuous, but there is less work in relating expressions to an observed event time such as time to death, response or relapse. When gene expressions are measured over time, there are methods for differentiating temporal patterns. However, methods have not yet been proposed for the survival analysis of longitudinally collected microarrays. Results: We describe an approach for the survival analysis of longitudinal gene expression data. We construct a measure of association between the time to an event and gene expressions collected over time. Statistical significance is addressed using permutations and control of the false discovery rate. Our proposed method is illustrated on a dataset from a multi-center research study of inflammation and response to injury that aims to uncover the biological reasons why patients can have dramatically different outcomes after suffering a traumatic injury (www.gluegrant.org). C1 Massachusetts Gen Hosp, Biostat Unit, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. RP Finkelstein, DM (reprint author), Massachusetts Gen Hosp, Biostat Unit, 50 Staniford St,Suite 560, Boston, MA 02114 USA. EM dfinkelstein@partners.org FU NIDDK NIH HHS [P30 DK040561-11, P30 DK040561]; NIGMS NIH HHS [U54-GM62119, U54 GM062119] NR 34 TC 5 Z9 5 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD NOV 1 PY 2006 VL 22 IS 21 BP 2643 EP 2649 DI 10.1093/bioinformatics/btl450 PG 7 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 099XC UT WOS:000241629600010 PM 17032680 ER PT J AU Biederman, J AF Biederman, Joseph TI The evolving face of pediatric mania SO BIOLOGICAL PSYCHIATRY LA English DT Editorial Material ID BIPOLAR DISORDER; COMORBIDITY C1 Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, Pediat Psychopharmacol Res Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Biederman, J (reprint author), Massachusetts Gen Hosp, Clin & Res Program Pediat Psychopharmacol, Pediat Psychopharmacol Res Unit, 55 Fruit St,Warren 705, Boston, MA 02114 USA. EM jbiederman@partners.org NR 18 TC 7 Z9 7 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 NOV 1 PY 2006 VL 60 IS 9 BP 901 EP 902 DI 10.1016/j.biopsych.2006.09.016 PG 2 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 100TL UT WOS:000241691600001 PM 17056392 ER PT J AU Althoff, RR Rettew, DC Faraone, SV Boomsma, DI Hudziak, JJ AF Althoff, Robert R. Rettew, David C. Faraone, Stephen V. Boomsma, Dorret I. Hudziak, James J. TI Latent class analysis shows strong heritability of the child behavior checklist-juvenile bipolar phenotype SO BIOLOGICAL PSYCHIATRY LA English DT Article DE ADHD; bipolar disorder; latent class analysis ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; DSM-IV ADHD; POPULATION-SAMPLE; AGED 6-11; TWINS; CBCL; ADOLESCENTS; SYMPTOMS; DEPRESSION AB Background: The Child Behavior Checklist (CBCL) has been used to provide a quantitative description of childhood bipolar disorder WAD), Many have reported that children in the clinical range on the Attention Problems (AP), Aggressive Behavior (AGG), and Anxious-Depressed (AID) syndromes simultaneously are more likely to meet the criteria for childhood BPAD. The purpose of this study was to determine if Latent Class Analysis (LCA) could identify beritable phenotypes representing the CBCL-Juvenile Bipolar (CBCL-JBD) profile and whether this phenotype demonstrates increased frequency of suicidal endorsement. Methods. The CBCL data were received by survey of mothers of twins in two large twin samples, the Netherlands Twin Registry. The setting for the study was the general community twin sample. Participants included 6246 10-year-old Dutch twins from the Netherlands Twin Registry. The main outcome measure consisted of the LCA on the items comprising the AP, AGG, and AID subscales and means from the suicidal items #18 and #91 within classes. Results: A 7 class model fit best for girls and an 8 class fit best for boys. The most common class for boys or girls was one with no symptoms. The CBCL-JBD phenotype was the least common-about 4-5% of the boys and girls. This class was the only one that bad significant elevations on the suicidal items of the CBCL. Gender differences were present across latent classes with girls showing no aggression without the CBCL-JBD phenotype and rarely showing attention problems in isolation. Evidence of high heritability of these latent classes was found with odds ratios. Conclusions: In a general population sample, LCA identities a CBCL-JBD phenotype latent class that is associated with high rates of suicidality, is highly heritable, and speaks to the comorbidity between attention problems, aggressive behavior, and anxious/depression in children. C1 Univ Vermont, Dept Psychiat, Div Behav Genet, Vermont Med Genet Res Program, Burlington, VT 05405 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. SUNY Upstate Med Univ, Dept Psychiat & Behav Sci, Syracuse, NY USA. Free Univ Amsterdam, Amsterdam, Netherlands. RP Hudziak, JJ (reprint author), Univ Vermont, Dept Psychiat, Div Behav Genet, Vermont Med Genet Res Program, Given Bldg,B229,1 S Prospect St, Burlington, VT 05405 USA. EM james.hudziak@uvm.edu OI Hudziak, James/0000-0001-9653-758X; Faraone, Stephen/0000-0002-9217-3982 FU NIMH NIH HHS [MH58799]; PHS HHS [NWO 575-25-006, NWO 904-57-94] NR 46 TC 69 Z9 69 U1 3 U2 11 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 NOV 1 PY 2006 VL 60 IS 9 BP 903 EP 911 DI 10.1016/j.biopsych.2006.02.025 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 100TL UT WOS:000241691600002 PM 16650832 ER PT J AU Boomsma, DI Rebollo, I Derks, EM van Beijsterveldt, TCEM Althoff, RR Rettew, DC Hudziak, JJ AF Boomsma, Dorret I. Rebollo, Irene Derks, Eske M. van Beijsterveldt, Toos C. E. M. Althoff, Robert R. Rettew, David C. Hudziak, James J. TI Longitudinal stability of the CBCL-juvenile bipolar disorder phenotype: A study in Dutch twins SO BIOLOGICAL PSYCHIATRY LA English DT Article DE childhood bipolar affective disorder; genetics; twins ID PREPUBERTAL CHILDREN; ATTENTION PROBLEMS; CLASSICAL TWIN; MANIA; ADHD; POWER; AGE; PHENOMENOLOGY; HERITABILITY; AGGRESSION AB Background: The Child Behavior Checklist-juvenile bipolar disorder phenotype (CBCL-JBD) is a quantitative phenotype that is based on parental ratings of the behavior of the child. The phenotype is predictive of DSM-IV characterizations of BD and has been shown to be sensitive and specific. Its genetic architecture differs from that for inattentive, aggressive, or anxious-depressed syndromes. The Purpose of this study is to assess the developmental stability of the CBCL-JBD phenotype across ages 7, 10, and 12 years in a large population-based twin sample and to examine its genetic architecture. Methods. Longitudinal data on Dutch mono- and dizygotic twin pairs (N = 8013 pairs) are analyzed to decompose the stability of the CBCL-JBD phenotype into genetic and environmental contributions. Results. Heritability of the CBCL-JBD increases with age (from 63% to 75%), whereas the effects of shared environment decrease (from 20% to 8%). The stability of the CBCL-JBD pbenotype is high, with correlations between .66 and. 77 across ages 7, 10, and 12 years. Genetic factors account for the majority of the stability of this phenotype. There were no sex differences in genetic architecture. Conclusions: Roughly 80% of the stability in childhood CBCL-JBD is a result of additive genetic effects. C1 Vrije Univ Amsterdam, Dept Biol Psychol, NL-1081 BT Amsterdam, Netherlands. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Univ Vermont, Dept Psychiat, Burlington, VT USA. RP Boomsma, DI (reprint author), Vrije Univ Amsterdam, Dept Biol Psychol, Van Boechorststr 1, NL-1081 BT Amsterdam, Netherlands. EM dorret@psy.vu.nl RI Rebollo Mesa, Irene/D-2678-2009; Derks, Eske/A-1652-2017; OI Rebollo Mesa, Irene/0000-0002-0264-9538; Derks, Eske/0000-0002-6292-6883; Hudziak, James/0000-0001-9653-758X FU NIMH NIH HHS [MH58799] NR 46 TC 36 Z9 37 U1 4 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD NOV 1 PY 2006 VL 60 IS 9 BP 912 EP 920 DI 10.1016/j.biopsych.2006.02.028 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 100TL UT WOS:000241691600003 PM 16735031 ER PT J AU Schaefer, HS Putnam, KM Benca, RM Davidson, RJ AF Schaefer, Hillary S. Putnam, Katherine M. Benca, Ruth M. Davidson, Richard J. TI Event-related functional magnetic resonance imaging measures of neural activity to positive social stimuli in pre- and post-treatment depression SO BIOLOGICAL PSYCHIATRY LA English DT Article DE depression; functional MRI; positive affect; psychosocial factors; antidepressant treatment; prefrontal cortex ID FRONTAL BRAIN ASYMMETRY; FACIAL EXPRESSIONS; MAJOR DEPRESSION; SEXUAL DYSFUNCTION; PLEASANT STIMULI; NEGATIVE AFFECT; AFFECTIVE STYLE; EMOTION; RECOVERY; AMYGDALA AB Background: Relationships between aberrant social functioning and depression have been explored via behavioral, clinical, and survey methodologies, highlighting their importance in the etiology of depression. The neural underpinnings of these relationships, however, have not been explored. Methods. Nine depressed participants and 14 never-depressed control subjects viewed emotional and neutral pictures at two functional magnetic resonance imaging (fMRI) scanning sessions approximately 22 weeks apart. In the interim, depressed patients received the antidepressant Venlafaxine. Positively rated images were parsed into three separate comparisons: social interaction, human faces, and sexual images; across scanning session, activation to these images was compared with other positively rated images. Results. For each of the three social stimulus types (social interaction, faces, sexual images), a distinguishable circuitry was activated equally in non-depressed control subjects and post-treatment depressed subjects but showed a hypo-response in the depressed group pre-treatment. These structures include regions of prefrontal, temporal, and parietal cortices, insula, basal ganglia, and the hippocampus. Conclusions: The neural hypo-response to positively valenced social stimuli that is observed in depression remits as response to antidepressant medication occurs, suggesting a state-dependent deficiency in response to positive social incentives, These findings underscore the importance of addressing social dysfunction in research and treatment of depression. C1 Univ Wisconsin, Waisman Lab Brain Imaging & Behav, Madison, WI 53705 USA. Univ Wisconsin, Dept Psychiat, Madison, WI 53705 USA. Boston Vet Adm, Med Ctr, Natl Ctr PTSD, Boston, MA USA. RP Davidson, RJ (reprint author), Univ Wisconsin, Waisman Lab Brain Imaging & Behav, 1500 Highland Ave,Rm T-225, Madison, WI 53705 USA. EM rjdavids@wisc.edu FU NIMH NIH HHS [P50-MH069315, R01-MH40747] NR 62 TC 75 Z9 81 U1 7 U2 14 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 NOV 1 PY 2006 VL 60 IS 9 BP 974 EP 986 DI 10.1016/j.biopsych.2006.03.024 PG 13 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 100TL UT WOS:000241691600011 PM 16780808 ER PT J AU Ballen, K AF Ballen, Karen TI Double cord blood transplantation in adults using a reduced intensity chemotherapy only conditioning regimen SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT 4th Annual International Cord Blood Transplantation Symposium CY MAY 19-20, 2006 CL Los Angeles, CA C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD NOV PY 2006 VL 12 IS 11 MA 5 BP 1219 EP 1219 DI 10.1016/j.bbmt.2006.08.007 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 104EH UT WOS:000241938700019 ER PT J AU Oral, E Rowell, SL Muratoglu, OK AF Oral, Ebru Rowell, Shannon L. Muratoglu, Orhun K. TI The effect of alpha-tocopherol on the oxidation and free radical decay in irradiated UHMWPE SO BIOMATERIALS LA English DT Article DE total hip arthroplasty; highly cross-linked polyethylene; oxidation resistance; free radicals; biomaterials ID MOLECULAR-WEIGHT POLYETHYLENE; ELECTRON-SPIN-RESONANCE; HIGH-DENSITY POLYETHYLENE; LIVED FREE-RADICALS; PARAMAGNETIC-RESONANCE; MECHANICAL-PROPERTIES; VITAMIN-E; ANTIOXIDANT ACTIVITY; ORTHOPEDIC UHMWPE; WEAR-RESISTANCE AB We developed a radiation cross-linked ultra-high molecular weight polyethylene (UHMWPE) stabilized with alpha-tocopherol (Vitamin E) as a bearing material in total joint replacements. The stabilizing effect of alpha-tocopherol on free radical reactions in UHMWPE is not well understood. We investigated the effect of alpha-tocopherol on the oxidation and transformation of residual free radicals during real-time aging of alpha-tocopherol-doped, irradiated UHMWPE (alpha TPE) and irradiated UHMWPE (control). Samples were aged at 22 degrees C (room temperature) in air, at 40 degrees C in air and at 40 degrees C in water for 7 months. During the first month, alpha TPE showed some oxidation at the surface, which stayed constant thereafter. Control exhibited substantial oxidation in the subsurface region, which increased with time. The alkyl/allyl free radicals transformed to oxygen centered ones in both materials; this transformation occurred faster in alpha-TPE. In summary, the real-time oxidation behavior of alpha-TPE was consistent with that observed using accelerated aging methods. This new UHMWPE is oxidation resistant and is expected to maintain its properties in the long term. (c) 2006 Published by Elsevier Ltd. C1 Massachusetts Gen Hosp, Harris Orthopaed Biomech & Biomat Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Muratoglu, OK (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Biomech, 55 Fruit St,GRJ 1206, Boston, MA 02114 USA. EM orhun@alum.mit.edu FU NIAMS NIH HHS [R01 AR051142, R01 AR051142-02, R01 AR051142-03] NR 48 TC 63 Z9 64 U1 2 U2 13 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 J9 BIOMATERIALS JI Biomaterials PD NOV PY 2006 VL 27 IS 32 BP 5580 EP 5587 DI 10.1016/j.biomaterials.2006.07.017 PG 8 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 088ER UT WOS:000240794900013 PM 16887182 ER PT J AU Szulc, ZM Bielawski, J Gracz, H Gustilo, M Mayroo, N Hannun, YA Obeid, LM Bielawska, A AF Szulc, Zdzislaw M. Bielawski, Jacek Gracz, Hanna Gustilo, Marietta Mayroo, Nalini Hannun, Yusuf A. Obeid, Lina M. Bielawska, Alicja TI Tailoring structure-function and targeting properties of ceramides by site-specific cationization SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE ceramide; cationic ceramides; ceramidoids; ceramide conjugates with pyridinium salts; CCPS-analogs; synthesis; LC-MS; NMR; cytotoxicity ID SHORT-CHAIN CERAMIDE; TANDEM MASS-SPECTROMETRY; ADENOCARCINOMA CELL-LINE; D-ERYTHRO-SPHINGOSINE; BREAST-CANCER CELLS; D-THREO-SPHINGOSINE; CARCINOMA-CELLS; TUMOR-GROWTH; LONG-CHAIN; ANTITUMOR-ACTIVITY AB In the course of our studies on compartment-specific lipid-mediated cell regulation, we identified an intimate connection between ceramides (Cers) and the mitochondria-dependent death-signaling pathways. Here, we report on a new class of cationic Cer mimics, dubbed ceramidoids, designed to act as organelle-targeted sphingolipids (SPLs), based on conjugates of Cer and dihydroceramide (dhCer) with pyridinium salts (CCPS and dhCCPS, respectively). Ceramidoids having the pyridinium salt unit (PSU) placed internally (alpha and gamma-CCPS) or as a tether (omega-CCPS) in the N-acyl moiety were prepared by N-acylation of sphingoid bases with different omega-bromo acids or pyridine carboxylic acid chlorides following capping with respective pyridines or alkyl bromides. Consistent with their design, these analogs, showed a significantly improved solubility in water, well-resolved NMR spectra in D2O, broadly modified hydrophobicity, fast cellular uptake, and higher anticancer activities in cells in comparison to uncharged counterparts. Structure-activity relationship (SAR) studies in MCF-7 breast carcinoma cells revealed that the location of the PSU and its overall chain length affected markedly the cytotoxic effects of these ceramidoids. All omega-CCPSs were more potent (IC50/48 h: 0.6-8.0 mu M) than their alpha/gamma-CCPS (IC50/48 h: 8-20 mu M) or D-erythro-C6-Cer (IC50/48 h: 15 mu M) analogs. omega-DhCCPSs were also moderately potent (IC(50/)48 h: 2.5-12.5 mu M). Long-chain omega-dhCCPSs were rapidly and efficiently oxidized in cells to the corresponding omega-CCPSs, as established by LC-MS analysis. CCPS analogs also induced acute changes in the levels and composition of endogenous Cers (upregulation of C16-, C14-, and C18-Cers, and downregulation of C24:0- and C24:1-Cers). These novel ceramidoids illustrate the feasibility of compartment-targeted lipids, and they should be useful in cell-based studies as well as potential novel therapeutics. (c) 2006 Elsevier Ltd. All rights reserved. C1 Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. N Carolina State Univ, Dept Mol & Struct Biochem, Raleigh, NC 27695 USA. Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Med Univ S Carolina, Ralph H Johnson Vet Adm Med Ctr, Charleston, SC 29425 USA. RP Bielawska, A (reprint author), Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. EM bielawsk@musc.edu OI Szulc, Zdzislaw M./0000-0003-1756-9028; obeid, lina/0000-0002-0734-0847 FU NCI NIH HHS [IP01CA097132]; NCRR NIH HHS [C06RR018823, RR17677]; NIA NIH HHS [AG16583] NR 94 TC 32 Z9 33 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD NOV 1 PY 2006 VL 14 IS 21 BP 7083 EP 7104 DI 10.1016/j.bmc.2006.07.016 PG 22 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 095YP UT WOS:000241344500002 PM 16919460 ER PT J AU Zhukovsky, MA Leikina, E Markovic, I Bailey, AL Chernomordik, LV AF Zhukovsky, Mikhail A. Leikina, Eugenia Markovic, Ingrid Bailey, Austin L. Chernomordik, Leonid V. TI Heterogeneity of early intermediates in cell-liposome fusion mediated by influenza hemagglutinin SO BIOPHYSICAL JOURNAL LA English DT Article ID INDUCED MEMBRANE-FUSION; VIRUS HEMAGGLUTININ; RECEPTOR-BINDING; PORE FORMATION; CONFORMATIONAL CHANGE; CYTOPLASMIC TAIL; LIPID VESICLES; 6-HELIX BUNDLE; EARLY-STAGE; PH AB To explore early intermediates in membrane fusion mediated by influenza virus hemagglutinin (HA) and their dependence on the composition of the target membrane, we studied lipid mixing between HA-expressing cells and liposomes containing phosphatidylcholine ( PC) with different hydrocarbon chains. For all tested compositions, our results indicate the existence of at least two types of intermediates, which differ in their lifetimes. The composition of the target membrane affects the stability of fusion intermediates at a stage before lipid mixing. For less fusogenic distearoyl PC-containing liposomes at 4 degrees C, some of the intermediates inactivate, and no intermediates advance to lipid mixing. Fusion intermediates that formed for the more fusogenic dioleoyl PC-containing liposomes did not inactivate and even yielded partial lipid mixing at 4 degrees C. Thus, a more fusogenic target membrane effectively blocks nonproductive release of the conformational energy of HA. Even for the same liposome composition, HA forms two types of fusion intermediates, dissimilar in their stability and propensity to fuse. This diversity of fusion intermediates emphasizes the importance of local membrane composition and local protein concentration in fusion of heterogeneous biological membranes. C1 NICHHD, Sect Membrane Biol, Cellular & Mol Biophys Lab, NIH, Bethesda, MD 20892 USA. RP Zhukovsky, MA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St,JFB 824, Boston, MA 02115 USA. EM Mikhail_Zhukovsky@dfci.harvard.edu FU Intramural NIH HHS NR 54 TC 5 Z9 5 U1 1 U2 5 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD NOV PY 2006 VL 91 IS 9 BP 3349 EP 3358 DI 10.1529/biophysj.106.088005 PG 10 WC Biophysics SC Biophysics GA 094GS UT WOS:000241228500021 PM 16905609 ER PT J AU Barry, MJ Delorenzo, MA Walker-Corkery, ES Lucas, FL Wennberg, DC AF Barry, Michael J. Delorenzo, Michael A. Walker-Corkery, Elizabeth S. Lucas, F. Lee Wennberg, David C. TI The rising prevalence of androgen deprivation among older American men since the advent of prostate-specific antigen testing: a population-based cohort study SO BJU INTERNATIONAL LA English DT Article DE prostate cancer; androgen deprivation; epidemiology; prostate-specific antigen ID QUALITY-OF-LIFE; RADICAL PROSTATECTOMY; HORMONAL-THERAPY; RADIATION-THERAPY; CANCER MORTALITY; NATURAL-HISTORY; SUPPRESSION; CARCINOMA; PATTERNS; TRENDS AB OBJECTIVE To investigate the effect of efforts in the early detection of prostate cancer using prostate-specific antigen (PSA) testing in the USA, by estimating the regional prevalence of androgen deprivation therapy (ADT) among older men in 1993-2000, and correlating the prevalence with early detection and aggressive treatment rates in 1987-91, as some authors predicted that ADT, a treatment traditionally reserved for advanced prostate cancer, would become less common over time as a result of such efforts. PATIENTS AND METHODS A sample of 5% of men who were Medicare beneficiaries was used in this prospective population-based cohort study. The main outcome measures were the overall prevalence of ADT (medical and surgical) in the cohort from 1993 to 2000, and correlations between rates of prostate procedures in the 306 USA hospital referral regions in 1987-91 and prevalence of ADT in those regions from 1993 to 2000. RESULTS The prevalence of ADT among these men in the USA increased steadily from 1.8% in 1993 to 2.9% in 2000 (P < 0.001). Regions with higher rates of prostate biopsy in 1987-91 had a higher prevalence of ADT in 1993, 1995 and 1997 (P < 0.05). Regions with higher rates of transurethral prostatectomy in 1987-91 had a higher prevalence of ADT in 1993-2000 (P < 0.01). Regions with higher rates of radical prostatectomy in 1987-91 had higher rates of ADT in 1993-99 (P < 0.05). CONCLUSIONS Widespread early detection and aggressive treatment for prostate cancer in the USA has been associated with more, not less, ADT among older men over time. C1 Massachusetts Gen Hosp, Med Practices Evaluat Ctr, Boston, MA 02114 USA. RP Barry, MJ (reprint author), Massachusetts Gen Hosp, Med Practices Evaluat Ctr, 50 Staniford St,95h Floor, Boston, MA 02114 USA. EM mbarry@partners.org FU AHRQ HHS [R01 HS010278, HS 10278]; NIA NIH HHS [P01 AG019783-06, AG 0189783, P01 AG019783] NR 34 TC 57 Z9 59 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 NOV PY 2006 VL 98 IS 5 BP 973 EP 978 DI 10.1111/j.1646-410X.2006.06416.x PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 092PU UT WOS:000241110600012 PM 16879443 ER PT J AU Wrighting, DM Andrews, NC AF Wrighting, Diedra M. Andrews, Nancy C. TI Interleukin induces hepcidin expression through STAT3 SO BLOOD LA English DT Article ID SIGNAL-TRANSDUCTION; IRON-METABOLISM; CHRONIC DISEASE; PROTEIN; ANEMIA; TRANSCRIPTION; INFLAMMATION; LIVER; MECHANISMS; GENES AB Iron homeostasis is maintained through meticulous regulation of circulating hepcidin levels. Hepcidin levels that are inappropriately low or high result in iron overload or iron deficiency, respectively. Although hypoxia, erythroid demand, iron, and inflammation are all known to influence hepcidin expression, the mechanisms responsible are not well defined. In this report we show that the inflammatory cytokine interleukin-6 (IL-6) directly regulates hepcidin through induction and subsequent promoter binding of signal transducer and activator of transcription 3 (STAT3). STAT3 is necessary and sufficient for the IL-6 responsiveness of the hepcidin promoter. Our findings provide a mechanism by which hepcidin can be regulated by inflammation or, in the absence of inflammatory stimuli, by alternative mechanisms leading to STAT3 activation. C1 Childrens Hosp, Karp Family Res Labs, Div Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Grad Program Biol & Biomed Sci, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Howard Hughes Med Inst, Chevy Chase, MD USA. RP Andrews, NC (reprint author), Childrens Hosp, Karp Family Res Labs, Div Hematol Oncol, RM 8-125,300 Longwood Ave, Boston, MA 02115 USA. EM nancy_andrews@hms.harvard.edu OI Andrews, Nancy/0000-0003-0243-4462 FU NHLBI NIH HHS [T32 HL07623]; NIDDK NIH HHS [R01 DK053813, R01 DK053813-10] NR 27 TC 378 Z9 405 U1 3 U2 14 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 1 PY 2006 VL 108 IS 9 BP 3204 EP 3209 DI 10.1182/blood-2006-06-027631 PG 6 WC Hematology SC Hematology GA 099IE UT WOS:000241586100052 PM 16835372 ER PT J AU Frohlich, LF Bastepe, M Abu-Zahra, HS Erben, RG Juppner, H AF Froehlich, L. F. Bastepe, M. Abu-Zahra, H. S. Erben, R. G. Jueppner, H. TI A mouse model of pseudohypoparathyroidism type Ib: Deletion of the NESP55 imprinting control region SO BONE LA English DT Meeting Abstract CT International Conference on Progress in Bone and Mineral Research 2006 CY NOV 16-18, 2006 CL Vienna, AUSTRIA SP Amer Soc Bone & Mineral Res, Ludwig Boltzmann Inst Osteology C1 Univ Vet Med, Inst Pathophysiol, Vienna, Austria. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 J9 BONE JI Bone PD NOV PY 2006 VL 39 IS 5 BP S14 EP S14 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 099HP UT WOS:000241584500062 ER PT J AU Sitara, D Bergwitz, C Erben, RG St-Arnaud, R Razzaque, MS Juppner, H Lanske, B AF Sitara, D. Bergwitz, C. Erben, R. G. St-Arnaud, R. Razzaque, M. S. Jueppner, H. Lanske, B. TI Molecular regulation of FGF-23-mediated homeostasis SO BONE LA English DT Meeting Abstract CT International Conference on Progress in Bone and Mineral Research 2006 CY NOV 16-18, 2006 CL Vienna, AUSTRIA SP Amer Soc Bone & Mineral Res, Ludwig Boltzmann Inst Osteology C1 Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Vet Med, Dept Nat Sci, Vienna, Austria. Shriners Hosp Crippled Children, Genet Unit, Montreal, PQ, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 J9 BONE JI Bone PD NOV PY 2006 VL 39 IS 5 BP S20 EP S20 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 099HP UT WOS:000241584500080 ER PT J AU Pai, SY DeMartiis, D Forino, C Cavagnini, S Lanfranchi, A Giliani, S Moratto, D Mazza, C Porta, F Imberti, L Notarangelo, LD Mazzolari, E AF Pai, S-Y DeMartiis, D. Forino, C. Cavagnini, S. Lanfranchi, A. Giliani, S. Moratto, D. Mazza, C. Porta, F. Imberti, L. Notarangelo, L. D. Mazzolari, E. TI Stem cell transplantation for the Wiskott-Aldrich syndrome: a single-center experience confirms efficacy of matched unrelated donor transplantation SO BONE MARROW TRANSPLANTATION LA English DT Article DE Wiskott-Aldrich syndrome; chimerism; immune reconstitution; WASP ID BONE-MARROW-TRANSPLANTATION; MEDIATED GENE-TRANSFER; T-CELL; SYNDROME PROTEIN; LENTIVIRAL VECTOR; FUNCTIONAL CORRECTION; HEMATOPOIETIC-CELLS; WASP; IMMUNE; MICE AB The treatment of Wiskott-Aldrich syndrome ( WAS), a once uniformly fatal disorder, has evolved considerably as the use of hematopoietic stem cell transplant has become more widespread. For the majority of patients who lack an human leukocyte antigen-identical sibling, closely matched unrelated donor bone marrow transplant (MUD BMT) at an early age is an excellent option that nevertheless is not uniformly chosen. We retrospectively analyzed our experience with transplantation in 23 patients with WAS from 1990 to 2005 at the University of Brescia, Italy, of whom 16 received MUD BMT. Myeloablative chemotherapy was well tolerated with median neutrophil engraftment at day 18, and no cases of grade III or IV graft-vs-host disease. Overall survival was very good with 78.2%(18/23) of the whole cohort and 81.2% (13/16) of MUD BMT recipients surviving. Among 18 survivors, full donor engraftment was detected in 12 patients, and stable mixed chimerism in all blood lineages in four patients. Deaths were limited to patients who had received mismatched related BMT or who had severe clinical symptomatology at the time of transplantation, further emphasizing the safety and efficacy of MUD BMT when performed early in the clinical course of WAS. C1 Univ Brescia, Dept Pediat, Spedali Civili, Terzo Serv Anal Chim Clin, I-25123 Brescia, Italy. Univ Brescia, Dept Pediat, I-25123 Brescia, Italy. Univ Brescia, Angelo Novicelli Inst Mol Med, I-25123 Brescia, Italy. Harvard Univ, Sch Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Hematol Oncol, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. RP Notarangelo, LD (reprint author), Univ Brescia, Dept Pediat, Spedali Civili, Terzo Serv Anal Chim Clin, I-25123 Brescia, Italy. EM notarang@med.unibs.it RI Notarangelo, Luigi/F-9718-2016 OI Notarangelo, Luigi/0000-0002-8335-0262 NR 30 TC 45 Z9 49 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0268-3369 J9 BONE MARROW TRANSPL JI Bone Marrow Transplant. PD NOV PY 2006 VL 38 IS 10 BP 671 EP 679 DI 10.1038/sj.bmt.1705512 PG 9 WC Biophysics; Oncology; Hematology; Immunology; Transplantation SC Biophysics; Oncology; Hematology; Immunology; Transplantation GA 101HP UT WOS:000241732200005 PM 17013426 ER PT J AU Dey, BR Spitzer, TR AF Dey, Bimalangshu R. Spitzer, Thomas R. TI Current status of haploidentical stem cell transplantation SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Review DE haploidentical; myeloablative; non-myeloablative; stem cell transplant ID VERSUS-HOST-DISEASE; BONE-MARROW-TRANSPLANTATION; NATURAL-KILLER-CELL; REGULATORY T-CELLS; MISMATCHED HEMATOPOIETIC TRANSPLANTS; REFRACTORY HEMATOLOGIC MALIGNANCIES; MIXED LYMPHOHEMATOPOIETIC CHIMERISM; SEVERE COMBINED IMMUNODEFICIENCY; RECIPIENT LEUKOCYTE INFUSIONS; DONOR LYMPHOCYTE INFUSIONS AB Haploidentical stem cell transplantation is an alternative transplant strategy for patients without an human leucocyte antigen-matched donor. The historical experience with haploidentical stem cell transplantation has been characterised by the immunological consequences of crossing a major histocompatibility barrier, namely graft-versus-host disease (GVHD), graft rejection and impaired immune reconstitution. Ex vivo T-cell depletion of the graft may reduce the risk of GVHD, but at the expense of a higher risk of engraftment failure and relapse of the underlying malignancy. Myeloablative transplant strategies using vigorously T-cell-depleted 'megadose' stem cells appear to have improved the outcomes of selected patients with acute leukaemia. Non-myeloablative stem cell transplantation strategies, in which mixed chimaerism as a platform for adoptive cellular immunotherapy is intentionally induced, show promise for limiting GVHD and lessening transplant-related mortality. Future approaches, based on promising preclinical and early clinical observations, may include selective allodepletion of the graft, and manipulation of the cellular environment post-transplant using selected cellular populations or immunomodulatory soluble factors. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bone Marrow Transplant Program,Dept Med, Boston, MA 02114 USA. RP Spitzer, TR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Bone Marrow Transplant Program,Dept Med, 55 Fruit St, Boston, MA 02114 USA. EM tspitzer@partners.org NR 139 TC 39 Z9 43 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD NOV PY 2006 VL 135 IS 4 BP 423 EP 437 DI 10.1111/j.1365-2141.2006.06300.x PG 15 WC Hematology SC Hematology GA 095XZ UT WOS:000241342900001 PM 16984391 ER PT J AU Sobrin, L Miller, JW AF Sobrin, L. Miller, J. W. TI Optical coherence tomography pseudo-macular hole appearance after photodynamic therapy SO BRITISH JOURNAL OF OPHTHALMOLOGY LA English DT Article ID CHOROIDAL NEOVASCULARIZATION; EYES C1 Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. RP Miller, JW (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM Joan_Miller@meei.harvard.edu NR 9 TC 0 Z9 0 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0007-1161 J9 BRIT J OPHTHALMOL JI Br. J. Ophthalmol. PD NOV PY 2006 VL 90 IS 11 BP 1434 EP 1435 DI 10.1136/bjo.2006.095356 PG 4 WC Ophthalmology SC Ophthalmology GA 097FJ UT WOS:000241432100032 PM 17057177 ER PT J AU Boland, GWL AF Boland, G. W. L. TI Government reform of the National Health Service: implications for radiologists and diagnostic services SO BRITISH JOURNAL OF RADIOLOGY LA English DT Editorial Material ID NHS AB Demand for radiology services within the National Health Service (NHS) continues unabated and current NHS operations cannot keep up with demand. Therefore, to meet this demand, the government has decided to outsource a significant number of investigations to the independent sector and will actively promote patient referrals to the new government sponsored Treatment Centres as they become available. This presents opportunities to patients, but threatens existing public sector providers (including doctors) as competition for radiology services may result in both loss of patient referrals and revenue to these providers. This article is a personal opinion and will focus on the current challenges facing the provision of radiology services in the NHS. I will suggest the possible negative outcomes for providers (NHS hospitals and staff alike) and will offer strategies, tactics and tools that can be employed to counter the threat to their existing services. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Boland, GWL (reprint author), Massachusetts Gen Hosp, Dept Radiol, White 270C,55 Fruit St, Boston, MA 02114 USA. EM gboland@partners.org NR 21 TC 6 Z9 6 U1 0 U2 3 PU BRITISH INST RADIOLOGY PI LONDON PA 36 PORTLAND PLACE, LONDON W1N 4AT, ENGLAND SN 0007-1285 J9 BRIT J RADIOL JI Br. J. Radiol. PD NOV PY 2006 VL 79 IS 947 BP 861 EP 865 DI 10.1259/bjr/80900968 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 104FV UT WOS:000241943300001 PM 16945933 ER PT J AU Fava, M Rush, AJ Alpert, JE Carmin, CN Balasubramani, GK Wisniewski, SR Trivedi, MH Biggs, MM Shores-Wilson, K AF Fava, Maurizio Rush, A. John Alpert, Jonathan E. Carmin, Cheryl N. Balasubramani, G. K. Wisniewski, Stephen R. Trivedi, Madhukar H. Biggs, Melanie M. Shores-Wilson, Kathy TI What clinical and symptom features and comorbid disorders characterize outpatients with anxious major depressive disorder: A replication and extension SO CANADIAN JOURNAL OF PSYCHIATRY-REVUE CANADIENNE DE PSYCHIATRIE LA English DT Article DE anxiety; depression; anxious depression; subtype; features ID STAR-ASTERISK-D; SEQUENCED TREATMENT ALTERNATIVES; ILLNESS RATING-SCALE; REPORT QIDS-SR; PSYCHOMETRIC EVALUATION; PSYCHIATRIC-DISORDERS; ELDERLY PATIENTS; QUICK INVENTORY; FAMILY-HISTORY; FOLLOW-UP AB Objective: We previously found that 46% of the first 1450 outpatients with depression participating in the multicentre Sequenced Treatment Alternatives to Relieve Depression (STAR*D) project qualified for the designation of anxious depression. This study was designed to replicate and extend our initial findings in a subsequent, larger cohort of outpatient STAR*D participants with nonpsychotic major depressive disorder (MDD). Methods: Baseline clinical and sociodemographic data were collected on 2337 consecutive STAR*D participants. A baseline 17-item Hamilton Depression Rating Scale Anxiety-Somatization factor score of 7 or higher was designated as anxious depression. We identified concurrent Axis I disorders with the Psychiatric Diagnostic Screening Questionnaire (PDSQ), using a 90% specificity threshold. Depressive symptoms were assessed by clinical telephone interview with the 30-item Inventory of Depressive Symptomatology-Clinician-Rated (IDS-C30). Results: The prevalence of anxious depression in this population was 45.1%. Patients with anxious MDD were significantly more likely to be in primary care settings and to be women, nonsingle, unemployed, Hispanic, less educated, and suffering from severe depression, both before and after adjustment for overall depression severity. Patients with anxious depression were significantly more likely to meet PDSQ thresholds for generalized anxiety disorder, panic disorder, obsessive-compulsive disorder, posttraumatic stress disorder, agoraphobia, hypochondriasis, and somatoform disorder, both before and after adjusting for baseline depression severity. Individuals with anxious depression were also significantly less likely to endorse IDS-C30 items concerning atypical features and were significantly more likely to endorse items concerning melancholic-endogenous depression features, both before and after adjusting for baseline depression severity. Conclusions: This study clearly replicates our previous STAR*D findings and supports the notion that anxious depression may be a valid diagnostic subtype of MDD, with distinct psychiatric comorbidities and clinical and sociodemographic features. C1 Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA 02114 USA. Massachusetts Gen Hosp, Depress Clin & Res Program, Boston, MA USA. Univ Texas, SW Med Ctr, Dept Clin Sci, Dallas, TX USA. Univ Texas, SW Med Ctr, Mood Disorders Res Program & Clin, Dallas, TX USA. Univ Illinois, Stress & Anxiety Disorders Clin, Chicago, IL USA. Univ Illinois, Stress & Anxiety Disorders Clin, Chicago, IL USA. Univ Illinois, Cognit Behav Therapy Program, Chicago, IL USA. Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Epdiemiol Data Ctr, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA 15260 USA. RP Fava, M (reprint author), Massachusetts Gen Hosp, Depress Clin & Res Program, 55 Fruit St Bulfinch 351, Boston, MA 02114 USA. EM mfava@partners.org RI Biggs, Dr. Melanie/C-1468-2010; Carmin, Cheryl/F-8004-2014; OI Rush, Augustus/0000-0003-2004-2382; Wisniewski, Stephen/0000-0002-3877-9860; Alpert, Jonathan/0000-0002-4332-908X FU NIMH NIH HHS [N01MH90003] NR 36 TC 75 Z9 82 U1 1 U2 6 PU CANADIAN PSYCHIATRIC ASSOC PI OTTAWA PA 141 LAURIER AVENUE WEST, STE 701, OTTAWA, ONTARIO K1P 5J3, CANADA SN 0706-7437 J9 CAN J PSYCHIAT JI Can. J. Psychiat.-Rev. Can. Psychiat. PD NOV PY 2006 VL 51 IS 13 BP 823 EP 835 PG 13 WC Psychiatry SC Psychiatry GA 116HK UT WOS:000242792900004 PM 17195602 ER PT J AU Chak, A Faulx, A Eng, C Grady, W Kinnard, M Ochs-Balcom, H Falk, G AF Chak, Amitabh Faulx, Ashley Eng, Charis Grady, William Kinnard, Margaret Ochs-Balcom, Heather Falk, Gary TI Gastroesophageal reflux symptoms in patients with adenocarcinoma of the esophagus or cardia SO CANCER LA English DT Article DE esophageal adenocarcinoma; Barrett esophagus; gastroesophageal reflux disease; cardia ID BARRETTS-ESOPHAGUS; GASTRIC CARDIA; ESOPHAGOGASTRIC JUNCTION; ENDOSCOPIC SURVEILLANCE; INTESTINAL METAPLASIA; ACID EXPOSURE; RISK-FACTOR; PREVALENCE; CANCER; DISEASE AB BACKGROUND. The efficacy of endoscopic screening for chronic gastroesophageal reflux symptoms of heartburn and regurgitation in adult subjects depends on the sensitivity of this strategy for detecting Barrett esophagus in subjects before the development of adenocarcinoma of the esophagus or cardia. The aim of the current study was to determine what proportion of patients with cancer of the esophagus or cardia would have been candidates for a screening endoscopy before their cancer diagnosis based on the presence and duration of preceding reflux symptoms. METHODS. All patients with adenocarcinoma of the esophagus, adenocarcinoma of the cardia, or long-segment Barrett esophagus presenting for endoscopy at 4 tertiary care and 2 Veterans Affairs (VA) hospitals were given a previously validated questionnaire to determine their recall of common gastroesophageal reflux symptoms. RESULTS. The study population of 375 subjects consisted primarily of 294 (78%) white men. Only 67 of 110 patients (61%) with adenocarcinoma of the esophagus and 8 of 21 patients (38%) with adenocarcinoma of the cardia recalled symptoms of heartburn or regurgitation being present for > 5 years before their diagnosis of cancer. Only 40 of 110 patients (36%) with adenocarcinoma. of the esophagus and 5 of 21 patients (24%) with adenocarcinoma of the cardia recalled weekly symptoms being present for > 5 years before their cancer diagnosis. Of the 244 patients with Barrett esophagus, 170 (70%) recalled heartburn or regurgitation for > 5 years and 89 patients (37%) recalled weekly symptoms for > 5 years. CONCLUSIONS. Current practice, which uses a screening strategy of performing endoscopy in patients with > 5 years of heartburn or regurgitation, can detect Barrett epithelium in only a limited proportion of those patients at risk for developing adenocarcinoma of the esophagus or adenocarcinoma of the cardia. C1 Univ Hosp Cleveland, Case Sch Med, Div Gastroenterol, Cleveland, OH 44106 USA. Case Western Reserve Univ, Ireland Canc Ctr, Cleveland, OH 44106 USA. Case Western Reserve Univ, Sch Med, Case Comprehens Canc Ctr, Cleveland, OH 44106 USA. Case Western Reserve Univ, Sch Med, Div Gastroenterol, Wade Pk Vet Affairs Med Ctr, Cleveland, OH 44106 USA. Ohio State Univ, Sch Med, Div Human Genet, Dept Med, Columbus, OH 43210 USA. Cleveland Clin Fdn, Genom Med Inst, Cleveland, OH 44195 USA. Vanderbilt Univ, Dept Med, Nashville, TN USA. Vanderbilt Univ, Dept Canc Biol, Nashville, TN USA. Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, R&D Serv, Seattle, WA USA. Case Western Reserve Univ, Sch Med, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA. Cleveland Clin Fdn, Ctr Swallowing & Esophageal Disorders, Dept Gastroenterol & Hepatol, Cleveland, OH 44195 USA. RP Chak, A (reprint author), Univ Hosp Cleveland, Case Sch Med, Div Gastroenterol, 11100 Euclid Ave, Cleveland, OH 44106 USA. EM Amitabh.chak@case.edu RI Ochs-Balcom, Heather/F-3500-2012; OI Falk, Gary/0000-0002-7143-1436; Eng, Charis/0000-0002-3693-5145 FU NIDDK NIH HHS [DK002800, DK061426, DK070863] NR 40 TC 35 Z9 37 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD NOV 1 PY 2006 VL 107 IS 9 BP 2160 EP 2166 DI 10.1002/cncr.22245 PG 7 WC Oncology SC Oncology GA 101YK UT WOS:000241777300008 PM 17019737 ER PT J AU Cairns, CP Viswanath, K AF Cairns, Catherine P. Viswanath, K. TI Communication and colorectal cancer screening among the uninsured: data from the Health Information National Trends Survey (United States) SO CANCER CAUSES & CONTROL LA English DT Article DE colorectal neoplasms; cancer screening; medically uninsured; disparities; communication ID INTERVENTIONS; MAMMOGRAPHY; INSURANCE; RATES AB Objective Colorectal cancer screening allows for both prevention and early detection of the disease, with early detection often resulting in improved prognosis. Too few Americans over 50 are screened for colorectal cancer, but among certain subpopulations screening rates are particularly low for various reasons. We examined the role of communication factors and insurance, with a specific focus on the uninsured to examine disparities in colorectal cancer screening. Methods We used Health Information National Trends Survey data to examine: disparities in colorectal cancer screening, by calculating proportions of subpopulations screened; and the association between communication and screening among the uninsured, by performing chi-square tests and simple logistic regression to examine the potential factors associated with screening. Results The uninsured were 64% less likely to be screened than the insured. Provider recommendation was the only significant communication measure, with the uninsured lacking a recommendation 98.5% less likely to be screened than those with one. Conclusions These data suggest expansion of programs of screening among the uninsured and more aggressive communication campaigns to promote the awareness and provider recommendation of screening as possible ways to increase screening and reduce mortality of colorectal cancer. C1 Boston Publ Hlth Commiss AIDS Program, Boston, MA 02118 USA. Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. Harvard Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Cairns, CP (reprint author), Boston Publ Hlth Commiss AIDS Program, 1010 Massachusetts Ave 2nd Floor, Boston, MA 02118 USA. EM ccairns@bphc.org; vish_viswanath@dfci.harvard.edu NR 26 TC 30 Z9 30 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD NOV PY 2006 VL 17 IS 9 BP 1115 EP 1125 DI 10.1007/s10552-006-0046-2 PG 11 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 089CB UT WOS:000240856600002 PM 17006717 ER PT J AU Letai, A AF Letai, Anthony TI Restoring cancer's death sentence SO CANCER CELL LA English DT Editorial Material ID BH3-ONLY PROTEINS; BH3 DOMAINS; BCL-2; BAX AB In this issue of Cancer Cell, two groups present data on the function of an antagonist of BCL-2, ABT-737. Both groups find that expression of MCL-1, an antiapoptotic protein related to BCL-2, is a key determinant of resistance to ABT-737. Lowering MCL-1 levels is an effective adjunct to BCL-2 antagonism, and both groups suggest ways that this might be accomplished practically in a clinical setting. The mechanism by which ABT-737 selectively kills cancer cells is discussed below in the context of these and prior reports of ABT-737's function. Antagonism of BCL-2 is an exciting anticancer strategy that may soon become a clinical reality. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Letai, A (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St,Dana 530B, Boston, MA 02115 USA. EM anthony_letai@dfci.harvard.edu NR 8 TC 18 Z9 19 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD NOV PY 2006 VL 10 IS 5 BP 343 EP 345 DI 10.1016/j.ccr.2006.10.014 PG 3 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 106WF UT WOS:000242132000001 PM 17097553 ER PT J AU Polyak, K AF Polyak, Kornelia TI The p27Kip1 tumor suppressor gene: Still a suspect or proven guilty? SO CANCER CELL LA English DT Editorial Material ID P27(KIP1); GROWTH AB The p27Kip1 cyclin-dependent kinase inhibitor is considered to be a tumor suppressor even though somatic mutations in p27Kip1 are only rarely detected in human tumors. On the other hand, overwhelming evidence indicates that its hemizygous or posttranscriptional loss plays an important role in tumorigenesis. Based on these data, p27Kip1 was classified as a haploinsufficient tumor suppressor whose protein level has to be fine-tuned for optimal function. However, a recent study links germline mutations in p27Kip1 to multiple endocrine neoplasia syndrome in rats and humans, thus establishing p27Kip1 as a bona fide tumor suppressor gene. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Polyak, K (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM kornelia_polyak@dfci.harvard.edu NR 10 TC 9 Z9 9 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD NOV PY 2006 VL 10 IS 5 BP 352 EP 354 DI 10.1016/j.ccr.2006.10.015 PG 3 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 106WF UT WOS:000242132000005 PM 17097557 ER PT J AU Sharma, SV Gajowniczek, P Way, IP Lee, DY Jiang, J Yuza, Y Classon, M Haber, DA Settleman, J AF Sharma, Sreenath V. Gajowniczek, Patrycja Way, Inna P. Lee, Diana Y. Jiang, Jane Yuza, Yuki Classon, Marie Haber, Daniel A. Settleman, Jeffrey TI A common signaling cascade may underlie "addiction" to the Src, BCR-ABL, and EGF receptor oncogenes SO CANCER CELL LA English DT Article ID CELL LUNG-CANCER; TYROSINE KINASE; MULTISTAGE CARCINOGENESIS; CYCLE PROGRESSION; LEUKEMIC-CELLS; FAMILY KINASE; GEFITINIB; APOPTOSIS; GROWTH; RAS AB "Oncogene addiction" describes an unexplained dependency of cancer cells on a particular cellular pathway for survival or proliferation. We report that differential attenuation rates of prosurvival and proapoptotic signals in oncogene-dependent cells contribute to cell death following oncogene inactivation. Src-, BCR-ABL-, and EGF receptor-dependent cells exhibit a similar profile of signal attenuation following oncogene inactivation characterized by rapid diminution of phospho-ERK, -Akt, and -STAT3/5, and a delayed accumulation of the proapoptotic effector phospho-p38 MAPK. These findings implicate a transient imbalance in survival and apoptotic oncogenic outputs in the apoptotic response to oncogene inactivation. Moreover, these observations implicate a common profile of signal attenuation for multiple oncogenes and suggest that "addiction" associated with apoptosis reflects an active rather than a passive process. C1 Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. RP Settleman, J (reprint author), Massachusetts Gen Hosp, Ctr Canc, 149 13th St, Charlestown, MA 02129 USA. EM settleman@helix.mgh.harvard.edu RI Tang, Amy/L-3226-2016 OI Tang, Amy/0000-0002-5772-2878 FU NCI NIH HHS [R01 CA115830, R01 CA115830-04] NR 38 TC 181 Z9 190 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD NOV PY 2006 VL 10 IS 5 BP 425 EP 435 DI 10.1016/j.ccr.2006.09.014 PG 11 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 106WF UT WOS:000242132000012 PM 17097564 ER PT J AU Johnson, BE Jackman, D Janne, PA AF Johnson, Bruce E. Jackman, David Janne, Pasi A. TI Impact of EGFR mutations on treatment of non-small cell lung cancer SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article; Proceedings Paper CT 21st Bristol-Myers-Squibb Nagoya International Cancer Treatment Symposium CY FEB 24-25, 2006 CL Nagoya, JAPAN DE receptor; epidermal growth factor; lung neoplasm; carcinoma; non-small cell lung cancer ID GROWTH-FACTOR-RECEPTOR; ACTIVATING MUTATIONS; GEFITINIB SENSITIVITY; ACQUIRED-RESISTANCE; PROLONGED SURVIVAL; TYROSINE KINASE; ERLOTINIB; GENE; INHIBITOR; ADENOCARCINOMAS AB Somatic mutations in the epidermal growth factor receptor (EGFR) have been identified in advanced non-small cell lung cancer (NSCLC) patients who achieve dramatic clinical and radiographic responses to treatment with the EGFR tyrosine kinase inhibitors (TKIs) gefitinib and erlotinib. Retrospective studies comparing outcomes of patients with and without EGFR mutations treated with EGFR-TKIs demonstrate that patients with EGFR mutations live significantly longer than those without mutations. In addition, patients with NSCLC and a somatic deletion mutation of exon 19 exhibit longer survival than patients with point mutations of exon 21. Secondary resistance mutations have also been identified. Patients exhibiting a somatic sensitizing mutation of EGFR who achieve partial response to gefitinib or erlotinib therapy eventually develop clinical resistance to treatment with EGFR-TKI. Approximately half of these resistant patients develop a detectable secondary acquired resistance mutation (T790M) in their tumor. New irreversible EGFR inhibitors have in vitro and in vivo evidence of antitumor activity against lung cancer cells harboring both the sensitizing and resistance mutations. These findings suggest that patients with advanced NSCLC bearing somatic EGFR mutations should receive treatment with an EGFR-TKI included as at least part of their initial therapy. Trials are starting to test the irreversible EGFR inhibitors in patients with NSCLC after they develop resistance to their initial treatment with gefitinib or erlotinib. C1 Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Dept Med, Sch Med, Boston, MA 02115 USA. RP Johnson, BE (reprint author), Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, 44 Binney St,D 1234, Boston, MA 02115 USA. EM BEJohnson@Partners.Org RI Mendez, Pedro /J-8955-2016 OI Mendez, Pedro /0000-0001-6713-7907 NR 25 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD NOV PY 2006 VL 58 SU 1 BP S5 EP S9 DI 10.1007/s00280-006-0309-3 PG 5 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 122AR UT WOS:000243198600002 ER PT J AU Zhou, W Heist, RS Liu, G Neuberg, DS Asomaning, K Su, L Wain, JC Lynch, TJ Giovannucci, E Christiani, DC AF Zhou, Wei Heist, Rebecca S. Liu, Geoffrey Neuberg, Donna S. Asomaning, Kofi Su, Li Wain, John C. Lynch, Thomas J. Giovannucci, Edward Christiani, David C. TI Polymorphisms of vitamin D receptor and survival in early-stage non-small cell lung cancer patients SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID TRANS-RETINOIC ACID; BREAST-CANCER; GENE POLYMORPHISMS; UNRELATED INDIVIDUALS; A ANTAGONIZES; UNITED-STATES; EXPRESSION; DISEASE; GROWTH; ASSOCIATION AB Our previous analysis suggested that surgery season in the summer time and high vitamin D intake are associated with improved survival in early-stage non-small cell lung cancer (NSCLC) patients. Here, we investigated the associations of vitamin D receptor WDR) polymorphisms of Cdx-2 G > A, Fok1 C > T, and BsmI C > T with overall survival (OS) and recurrencefree survival (RFS) in 373 early-stage NSCLC patients. The data were analyzed using log-rank test and Cox proportional hazards models. The median follow-up time was 71 months (range, 0.1-140 months), with 186 deaths and 127 recurrences. There was no association between VDR polymorphisms and survival, overall or among adenocarcinoma patients. Among squamous cell carcinoma (SCC) patients, the G/A+A/A genotype group of the Cdx-2 polymorphism was associated with better OS: the 5-year OS rates were 41% [95% confidence interval (95% CI), 28-531 for the GIG and 55% (95% CI, 39-71) for the G/A+A/A genotypes, respectively (P = 0.04, log-rank test), with the adjusted hazard ratio of 0.56 (95% CI, 0.33-0.95) for G/A+A/A versus GIG. For the joint effects of the three polymorphisms, subjects with two or more "protective" alleles have better OS among SCC patients, with the adjusted hazard ratios of 0.20 (95% CI, 0.09-0.48), 0.40 (95% CI, 0.19-0.87), and 0.43 (95% CI, 0.19-0.97), respectively, for subjects with two, three, and four or more "protective" alleles when compared with subjects with zero or one "protective" allele (Pt,,nd = 0.71). Similar associations were found in haplotype analysis and for RFS among SCC patients. In conclusion, VDR polymorphisms may be associated with improved survival among SCC patients of early-stage NSCLC. C1 Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Dept Environm Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Biostat & Computat Biol, Dana Farber Canc Inst, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg, Thorac Surg Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. RP Zhou, W (reprint author), Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Dept Environm Hlth, 665 Huntington Ave, Boston, MA 02115 USA. EM wzhou@hsph.harvard.edu RI Liu, Geoffrey/N-4421-2016 FU NCI NIH HHS [ES/CA 06409, CA092824, CA119650-01A1, CA090578, CA074386]; NIEHS NIH HHS [ES00002] NR 35 TC 38 Z9 39 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 NOV PY 2006 VL 15 IS 11 BP 2239 EP 2245 DI 10.1158/1055-9965.EPI-06-0023 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 107DG UT WOS:000242150300037 PM 17119052 ER PT J AU Carlson, RW O'Neill, AM Goldstein, LJ Sikic, BI Abramson, N Stewart, JA Davidson, NE Wood, WC AF Carlson, Robert W. O'Neill, Anne M. Goldstein, Lori J. Sikic, Branimir I. Abramson, Neil Stewart, James A. Davidson, Nancy E. Wood, William C. TI A pilot phase II trial of valspodar modulation of multidrug resistance to paclitaxel in the treatment of metastatic carcinoma of the breast (E1195): A trial of the eastern cooperative oncology group SO CANCER INVESTIGATION LA English DT Article DE breast neoplasms; multidrug resistance; paclitaxel; valdospar ID COLONY-STIMULATING FACTOR; 3-HOUR INFUSION; SDZ PSC-833; CANCER; CHEMOTHERAPY; EXPRESSION; CELLS AB Background: To assess the activity and toxicity of valspodar (PSC-833) in combination with paclitaxel in women with anthracycline refractory, metastatic breast cancer. Patients and Methods: Limited, multi-institutional, Phase II trial of valspodar at 5 mg/kg/dose orally every 6 hours for 12 doses in combination with paclitaxel 70 mg/m(2) administered intravenously as a 3-hour infusion beginning 4 hours after the fifth dose of valspodar, every 3 weeks. Eligible patients had bi-dimensionally measurable metastatic carcinoma of the breast, prior anthracycline therapy or a medical contraindication to anthracycline therapy, no more than one prior chemotherapy for recurrent or metastatic breast cancer, and adequate organ function. Treatment was continued until disease progression or unacceptable toxicity. Results: Thirty-four patients are evaluable for response and 37 for toxicity. Two (6 percent) patients achieved a complete response and 5 (15 percent) a partial response for an objective response rate of 21 percent (95 percent confidence interval of 9 to 38 percent). Median duration of response was 9.7 months (95 percent confidence interval 8.0-17.2 months), median time to progression was 3.3 months (95 percent confidence interval 2.0-4.2 months), and median survival was 12 months (95 percent confidence interval 8.1-17.3 months). The toxicity experienced was acceptable. Conclusions: Combination valspodar plus paclitaxel is an active regimen and has acceptable toxicity. The combination is not clearly more active than single agent paclitaxel. C1 Stanford Univ, Stanford, CA 94305 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Baptist Canc Inst, Jacksonville, FL USA. Univ Wisconsin, Madison, WI 53706 USA. Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Emory Univ, Atlanta, GA 30322 USA. RP Carlson, RW (reprint author), Stanford Univ, 875 Blake Wilbur Dr, Stanford, CA 94305 USA. EM rcarlson@stanford.edu FU NCI NIH HHS [CA21115, CA16116, CA21076, CA23318, CA27525, CA66636] NR 25 TC 23 Z9 24 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0735-7907 J9 CANCER INVEST JI Cancer Invest. PD NOV PY 2006 VL 24 IS 7 BP 677 EP 681 DI 10.1080/07357900600981349 PG 5 WC Oncology SC Oncology GA 107YU UT WOS:000242207700003 PM 17118777 ER PT J AU Agoulnik, IU Vaid, A Nakka, M Alvarado, M Bingman, WE Erdem, H Frolov, A Smith, CL Ayala, GE Ittmann, MM Weigel, NL AF Agoulnik, Irina U. Vaid, Ajula Nakka, Manjula Alvarado, Misty Bingman, William E., III Erdem, Halime Frolov, Anna Smith, Carolyn L. Ayala, Gustavo E. Ittmann, Michael M. Weigel, Nancy L. TI Androgens modulate expression of transcription intermediary factor 2, an androgen receptor coactivator whose expression level correlates with early biochemical recurrence in prostate cancer SO CANCER RESEARCH LA English DT Article ID CELL-PROLIFERATION; THERAPY; KINASE; GENE; INACTIVATION; RESISTANCE; MECHANISM; CARCINOMA; SURVIVAL; DOMAINS AB Prostate cancer is an androgen-dependent disease; metastatic prostate cancer is typically treated by androgen receptor (AR) blockade. Recurrence after androgen ablation and evidence that AR continues to play a role in many prostate cancers has led to an examination of other factors that potentiate AR activity. AR is a ligand-activated transcription factor whose activity is regulated not only by hormone but also by the levels of coactivators recruited by AR to facilitate transcription. We sought to assess the consequences of reducing expression of the transcription intermediary factor 2 (TIF2) coactivator on prostate cancer cell growth and AR action in cell lines to examine TIF2 expression in prostate cancer and to correlate expression with clinical outcome. Depletion of TIF2 reduced expression of AR-induced target genes and slowed proliferation of AR-dependent and AR-independent prostate cancer cells. Remarkably, we found that TIF2 expression is directly repressed by high levels of androgens in multiple AR-expressing cell lines. Expression of a reporter containing 5'-flanking region of the TIF2 was repressed both by androgens and by the antagonist, Casodex. Expression of TIF2 correlates with biochemical (prostate-specific antigen) recurrence (P = 0.0136). In agreement with our in vitro findings, the highest expression of TIF2 was found in patients whose cancer relapsed after androgen ablation therapy, supporting the idea that AR blockade might activate pathways that lead to stimulation of AR-dependent and AR-independent proliferation of prostate epithelium. The elevated expression of TIF2 at low hormone levels likely aids in inducing AR activity under these conditions; treatment with Casodex has the potential to counteract this induction. C1 Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. Baylor Coll Med, Dept Urol, Houston, TX 77030 USA. Michael E DeBakey Dept Vet Affairs Med Ctr, Houston, TX USA. RP Weigel, NL (reprint author), Baylor Coll Med, Dept Mol & Cellular Biol, 1 Baylor Plaza, Houston, TX 77030 USA. EM nweigel@bcm.edu OI Agoulnik, Irina/0000-0003-4889-0324 FU NCI NIH HHS [CA58204]; NIDDK NIH HHS [DK65252, T32-DK07763] NR 29 TC 106 Z9 106 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 NOV 1 PY 2006 VL 66 IS 21 BP 10594 EP 10602 DI 10.1158/0008-5472.CAN-06-1023 PG 9 WC Oncology SC Oncology GA 101ZY UT WOS:000241781600050 PM 17079484 ER PT J AU Fuchs, C Mitchell, EP Hoff, PM AF Fuchs, Charles Mitchell, Edith P. Hoff, Paulo M. TI Irinotecan in the treatment of colorectal cancer SO CANCER TREATMENT REVIEWS LA English DT Review DE cotorectat cancer; metastatic; adjuvant; neoadjuvant; irinotecan; bevacizumab ID MULTICENTER RANDOMIZED-TRIAL; PHASE-II TRIAL; 1ST-LINE TREATMENT; INDUCED DIARRHEA; ACTIVE METABOLITE; FLUOROURACIL FAILURE; CONTINUOUS-INFUSION; PLUS IRINOTECAN; LEUCOVORIN; CPT-11 AB Irinotecan, a water-soluble, semisynthetic derivative of camptothecin, is a key component of first- and second-line treatment regimens for metastatic colorectal cancer (CRC). In the first-line treatment of metastatic CRC, the results of two prospective, multicenter phase III trials have shown that the combination of irinotecan with bolus or infusional 5-fluorouracit (5FU)/teucovorin (LV) can significantly prolong survival compared with 5FU/LV atone, with a manageable side effects profile. In addition, irinotecan-based regimens, with or without oxaliplatin, may improve resectability of metastases and further increase patient survival. Studies of irinotecan in the first-tine setting in combination with newer agents, such as bevacizumab, have shown impressive overall survival. In the second-line setting, irinotecan has demonstrated efficacy superior to that of best supportive care. Initial studies of irinotecan plus bolus 5FU/LV and the preliminary results from trials of irinotecan plus infusional 5FU/LV in the adjuvant setting, have been disappointing; however, for the Largest trial, the Pan-European Trial in Adjuvant Colon Cancer, results with sufficient follow-up are pending. Irinotecan has an acceptable tolerability profile and is not associated with cumulative toxicities in patients with metastatic CRC; regimens containing irinotecan extend treatment duration and improve survival. New regimens and adjunctive therapies are being explored to reduce the incidence of common complications of irinotecan treatment, such as diarrhea and neutropenia. (c) 2006 Elsevier Ltd. All rights reserved. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Thomas Jefferson Univ, Philadelphia, PA 19107 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. RP Fuchs, C (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM charles_fuchs@dfci.harvard.edu; edith.mitchell@jefferson.edu; phoff@mdanderson.org NR 70 TC 54 Z9 58 U1 2 U2 8 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0305-7372 J9 CANCER TREAT REV JI Cancer Treat. Rev. PD NOV PY 2006 VL 32 IS 7 BP 491 EP 503 DI 10.1016/j.ctrv.2006.07.001 PG 13 WC Oncology SC Oncology GA 099FX UT WOS:000241579800001 PM 16959432 ER PT J AU North, PE Waner, M Buckmiller, L James, CA Mihm, MC AF North, Paula E. Waner, Milton Buckmiller, Lisa James, Charles A. Mihm, Martin C., Jr. TI Vascular tumors of infancy and childhood: beyond capillary hemangioma SO CARDIOVASCULAR PATHOLOGY LA English DT Review DE hemangioma; tufted angiotna; kaposiform hemangioendothelioma ID RESPONSE MODIFIER IMIQUIMOD; KASABACH-MERRITT PHENOMENON; INFANTILE HEMANGIOMA; KAPOSIFORM HEMANGIOENDOTHELIOMA; ENDOTHELIAL-CELLS; CONGENITAL HEMANGIOMA; JUVENILE HEMANGIOMA; TRYPTOPHAN CATABOLISM; 5-PERCENT CREAM; TUFTED ANGIOMA AB Vascular tumors of infancy and childhood represent a number of clinicopathologically distinct entities for which precise histopathological diagnosis is often essential in determining effective therapeutic approach. Unfortunately, pathologists and clinicians alike have traditionally tended to lump these tumors, in addition to small vessel vascular malformations, under overly generic terms like capillary hemangioma that do little, if anything, to guide proper clinical management. In the last decade this nosologic oversimplification has begun to wane as important new diagnostic tools and better understanding of etiology have evolved, facilitated by international recognition of the need for a multidisciplinary approach in dealing with these perplexing and often clinically devastating lesions. This article provides a brief historical perspective on this progress, and then focuses on the cur-rent clinical, histological, and immunophenotypical features that distinguish the major types of vascular tumors of infancy and childhood, also reviewing new evidence regarding their mechanisms of pathogenesis. (C) 2006 Elsevier Inc. All rights reserved. C1 Med Coll Wisconsin, Childrens Hosp Wisconsin, Dept Pathol, Milwaukee, WI 53226 USA. Univ Arkansas Med Sci, Dept Otolaryngol, Little Rock, AR 72202 USA. Arkansas Childrens Hosp, Little Rock, AR 72202 USA. Univ Arkansas Med Sci, Dept Radiol, Little Rock, AR 72202 USA. Vasc & Birthmarks Inst New York, New York, NY USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP North, PE (reprint author), Med Coll Wisconsin, Childrens Hosp Wisconsin, Dept Pathol, 9000 W Wisconsin Ave, Milwaukee, WI 53226 USA. EM pnorth@mcw.edu NR 74 TC 50 Z9 58 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1054-8807 J9 CARDIOVASC PATHOL JI Cardiovasc. Pathol. PD NOV-DEC PY 2006 VL 15 IS 6 BP 303 EP 317 DI 10.1016/j.carpath.2006.03.001 PG 15 WC Cardiac & Cardiovascular Systems; Pathology SC Cardiovascular System & Cardiology; Pathology GA 111UA UT WOS:000242479200001 PM 17113009 ER PT J AU McNicholas-Bevensee, CM DeAndrade, KB Bradley, WE Dell'Italia, LJ Lucchesi, PA Bevensee, MO AF McNicholas-Bevensee, Carmel M. DeAndrade, Kevin B. Bradley, Wayne E. Dell'Italia, Louis J. Lucchesi, Pamela A. Bevensee, Mark O. TI Activation of gadolinium-sensitive ion channels in cardiomyocytes in early adaptive stages of volume overload-induced heart failure SO CARDIOVASCULAR RESEARCH LA English DT Article DE calcium (cellular); heart failure; ion channels; stretch; membrane currents ID VENTRICULAR MYOCYTES; CARDIAC-HYPERTROPHY; CATION CURRENT; RAT; MECHANISMS; CURRENTS; CELLS AB Objective: The objective of this study was to investigate whether gadolinium, (Gd3+)-sensitive stretch-activated ion channels (SAC) are basally active in left ventricular (LV) myocytes in early stages of heart failure (HF) induced by volume overload. Methods: The aortocaval fistula (ACF) model was employed to induce HF due to volume overload in rat. At specific time-points, LV myocytes were acutely isolated using a modified Langendorff apparatus. Whole-cell currents were measured using the patch-clamp technique and intracellular Ca2+(Ca-i(2+)) was examined using fluorescence imaging and the Ca2+ -sensitive dye Fura-2. Results: Current-voltage data were obtained from sham and ACF myocytes at 5-d and 2-, 6-, 8- and 10-wk post surgery. Compared to data from matching sham rats, a 10 mu M Gd3+-sensitive current at -100 mV comprised a larger fraction of total cur-rent in myocytes from 5-d, 2wk, and 6-wk ACF rats. In general, the Gd3+-sensitive current contributed to inward currents at mV <=-80 and outward currents at >+20 mV The enhanced Gd3+-sensitive current was absent in myocytes from 8- and 10-wk ACF rats. 10 or 100 mu M Gd3+ had no appreciable effect on resting Ca-i(2+) of myocytes from 5-d ACF or corresponding sham rats. The Gd3+-sensitive current in 5-d ACF myocytes was i) sensitive to the cation-selective SAC inhibitor, GsMTx-4, ii) non-selective for Na+/K+, and iii) impermeable to Ca2+ Conclusion: A basally-active, Gd3+- and GsMTx-4-sensitive SAC current that is non-selective for Na+ and K+, but impermeable to Ca2+ under resting conditions is transiently elevated in LV myocytes from rats in early stages of volume overload-induced HF. (c) 2006 European Society of Cardiology. Published by Elsevier B.V. All rights reserved. C1 Univ Alabama, Dept Physiol & Biophys, Birmingham, AL 35294 USA. Univ Alabama, Div Cardiovasc Dis, Dept Med, Birmingham, AL 35294 USA. Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. RP McNicholas-Bevensee, CM (reprint author), Univ Alabama, Dept Physiol & Biophys, 868 McCallum Basic Hlth Sci Bldg,1918 Univ Blvd, Birmingham, AL 35294 USA. EM carmel@physiology.uab.edu RI Lucchesi, Pamela/E-3558-2011 FU NHLBI NIH HHS [T35 HL74371] NR 27 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6363 J9 CARDIOVASC RES JI Cardiovasc. Res. PD NOV 1 PY 2006 VL 72 IS 2 BP 262 EP 270 DI 10.1016/j.cardiores.2006.08.001 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 101AR UT WOS:000241711800009 PM 16959228 ER PT J AU Doebis, C Schu, S Ladhoff, J Busch, A Beyer, F Reiser, J Nicosia, RF Broesel, S Volk, HD Seifert, M AF Doebis, Cornelia Schu, Sabine Ladhoff, Juliane Busch, Annette Beyer, Florian Reiser, Jakob Nicosia, Roberto F. Broesel, Sabine Volk, Hans-Dieter Seifert, Martina TI An anti-major histocompatibility complex class I intrabody protects endothelial cells from an attack by immune mediators SO CARDIOVASCULAR RESEARCH LA English DT Article DE endothelial cell; gene therapy; intrabody; tissue engineering ID GROWTH-FACTOR RECEPTOR-2; ALLOGRAFT-REJECTION; GENE-TRANSFER; VITRO ENDOTHELIALIZATION; BYPASS GRAFTS; CLINICAL-EXPERIENCE; NONDIVIDING CELLS; RNA INTERFERENCE; LANGERHANS CELL; MHC AB Objective: In vitro endothelialization has significantly improved the overall outcome of artificial prostheses in cardiovascular bypass surgery. A drawback of this tissue-engineering method remains the limited availability of suitable autologous endothelial cells (EC), especially in aged patients. Allogeneic EC with high proliferative capacity represent a potentially valuable alternative to a patient-specific vascular transplant. However, such cells carry the risk of being rejected due to Major Histocompatibility Complex (MHC) mismatches. Methods: We investigated the effects of a very potent, intracellularly expressed antibody directed against MHC class I molecules, referred to as alpha-rat MHC I single chain variable fragment (sFv) intrabody. The intrabody was stably expressed in rat aortic EC (RAEC) following lentiviral vector-mediated gene transfer. The functional consequence of the MHC I down-regulation was tested in an allogeneic setting in two different in vitro assays. Results: Stable expression of the a-rat MHC I sFv intrabody resulted in a highly efficient depletion of surface MHC I. Thereby those RAEC which displayed low MHC I levels over extended periods of time were protected against killing by allo-specific, cytotoxic T cells (CTL) and by allo-antibody/complement-mediated lysis. Conclusions: These results demonstrate that intrabody-mediated down-regulation of MHC I reduces the immunogenicity of RAEC which may provide a suitable alternative supply for the lining of vascular prostheses. (c) 2006 European Society of Cardiology. Published by Elsevier B.V. All rights reserved. C1 Charite Univ Med Berlin, Inst Med Immunol, D-10117 Berlin, Germany. Louisiana State Univ, Hlth Sci Ctr, Gene Therapy Program, New Orleans, LA 70112 USA. Vet Affairs Puget Sound Hlth Care Syst, Div Pathol & Lab Med, Seattle, WA 98108 USA. RP Seifert, M (reprint author), Charite Univ Med Berlin, Inst Med Immunol, Monbijoustr 2A, D-10117 Berlin, Germany. EM martina.seifert@charite.de FU NHLBI NIH HHS [HL52585]; NINDS NIH HHS [NS044832] NR 37 TC 6 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6363 J9 CARDIOVASC RES JI Cardiovasc. Res. PD NOV 1 PY 2006 VL 72 IS 2 BP 331 EP 338 DI 10.1016/j.cardiores.2006.08.005 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 101AR UT WOS:000241711800016 PM 16963004 ER PT J AU Jaff, MR Hadley, G Hermiller, JB Simonton, C Hinohara, T Cannon, L Reisman, M Braden, G Fletcher, DR Zapien, M Chou, TM DiDonato, K AF Jaff, M. R. Hadley, G. Hermiller, J. B. Simonton, C. Hinohara, T. Cannon, L. Reisman, M. Braden, G. Fletcher, D. R. Zapien, M. Chou, T. M. DiDonato, K. TI The safety and efficacy of the StarClose (R) Vascular Closure System: The ultrasound substudy of the CLIP study SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE vessel closure; vascular access; arteriotomy; arterial sheath; femoral artery; vascular ultrasound; cardiac catheterization ID DEVICE; CATHETERIZATION; FEASIBILITY; SITES AB Background: The StarClose(R) Vascular Closure System (Abbott Vascular, Redwood City, CA) features a nitinol clip that is designed to achieve closure of the femoral arteriotomy access site. The CLIP Study was performed to assess the safety and efficacy of StarClose when compared with standard manual compression following 5-6 French diagnostic or interventional percutaneous procedures. A substudy of this trial was designed to assess the utility of duplex ultrasonography to assess patency of the femoral artery and to determine access site complications (pseudoaneurysm, arteriovenous fistula, hematoma, deep vein thrombosis) in a multicenter prospective trial. This is the report of the duplex ultrasound (DUS) substudy of the CLIP trial. Methods: A total of 17 U.S. sites enrolled 596 subjects with 483 subjects randomized at a 2:1 ratio to receive StarClose or manual compression of the arteriotomy after a percutaneous procedure. The study included roll-in (n = 113), diagnostic (n = 208), and interventional (n = 275) arms with a primary safety endpoint of major vascular complications through 30 days and a primary efficacy endpoint of postprocedure time to hemostasis. A substudy of the CLIP interventional arm evaluated DUS images of the closure site at five study sites, targeting 100 subjects at day 30 following hemostasis. The DUS protocol was devised and implemented by an independent vascular ultrasound core laboratory with extensive experience in vascular device trials. DUS inguinal region from 6 cm proximal to 6 cm distal to the arteriotomy puncture was performed. A qualitative examination was performed to determine the presence of iatrogenic vascular injuries: hematoma, pseudoaneurysm (PSA), arteriovenous fistula (AVF), and arterial/venous thrombosis or stenosis using 2-dimensional gray scale, color, and focused Doppler images. Results: DUS of 96 subjects randomized to StarClose (n = 71) and compression (n = 25) were performed and evaluated. There was no evidence of hematoma, PSA, or AVF observed in the StarClose group. No StarClose subjects in the substudy had a PSA or AVF. All patients in the substudy demonstrated patency of the access site artery and vein without thrombosis or stenosis. Finally, in the entire study cohort, no clinically-driven DUS studies demonstrated iatrogenic vascular injury or vessel thrombosis in the StarClose treated patients. Conclusion: DUS, a safe and reliable method for determining the safety and efficacy of access site closure devices, is a reliable, safe, inexpensive and accurate method of assessing vascular access site complications in multicenter trials. In this substudy of the CLIP study, DUS found no statistical difference in access site complications between the StarClose and manual compression groups. Both groups maintained vessel patency without stenosis, thrombosis, hematoma, pseudoaneurysm, or AV fistula. (C) 2006 Wiley-Liss, Inc. C1 Massachusetts Gen Hosp, Vasc Ultrasound Core Lab, Boston, MA 02114 USA. St Vincent Hosp & Hlth Ctr, Indianapolis, IN USA. Carolinas Med Ctr, Charlotte, NC 28203 USA. Sequoia Hosp, Dept Cardiovasc Med & Coronary Intervent, Redwood City, CA USA. No Michigan Hosp, Cardiac & Vasc Res Ctr No Ohio, Petoskey, MI USA. Swedish Med Ctr, Seattle, WA USA. Cardiol Specialists N Carolina, Dept Cardiovasc Res, Winston Salem, NC USA. Abbott Vasc Devices, Clin Affairs, Redwood City, CA USA. Univ Calif San Francisco, Med Ctr, Cardiac Catheterizat Lab, San Francisco, CA 94143 USA. RP Jaff, MR (reprint author), Massachusetts Gen Hosp, Vasc Ultrasound Core Lab, 62 Staniford St, Boston, MA 02114 USA. EM mjaff@partners.org NR 9 TC 29 Z9 31 U1 0 U2 0 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 NOV PY 2006 VL 68 IS 5 BP 684 EP 689 DI 10.1002/ccd.20898 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 102QE UT WOS:000241826700005 PM 17039509 ER PT J AU Shoelson, SE AF Shoelson, Steven E. TI Banking on ATM as a new target in metabolic syndrome SO CELL METABOLISM LA English DT Editorial Material ID ATAXIA-TELANGIECTASIA AB In this issue of Cell Metabolism, Semenkovich and his colleagues show that ATM, a protein well known for its roles in the cellular response to DNA breaks, may also be linked to metabolic and cardiovascular diseases (Schneider et al., 2006). ATM seemingly does this by inhibiting JNK, a stress kinase involved in inflammation with related effects in insulin resistance and atherosclerosis. In an interesting twist, the authors show that chloroquine, an antimalarial drug, also activates ATM, which inhibits JNK, and improves insulin sensitivity and cardiovascular effects. These findings provide potential new insights into the pathogenesis and treatment of metabolic syndrome. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA. RP Shoelson, SE (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. NR 7 TC 15 Z9 15 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1550-4131 J9 CELL METAB JI Cell Metab. PD NOV PY 2006 VL 4 IS 5 BP 337 EP 338 DI 10.1016/j.cmet.2006.10.009 PG 2 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 103JU UT WOS:000241882300003 PM 17084707 ER PT J AU Weydt, P Pineda, VV Torrence, AE Libby, RT Satterfield, TF Lazarowski, ER Gilbert, ML Morton, GJ Bammler, TK Strand, AD Cui, LB Beyer, RP Easley, CN Smith, AC Krainc, D Luquet, S Sweet, IR Schwartz, MW La Spada, AR AF Weydt, Patrick Pineda, Victor V. Torrence, Anne E. Libby, Randell T. Satterfield, Terrence F. Lazarowski, Eduardo R. Gilbert, Merle L. Morton, Gregory J. Bammler, Theodor K. Strand, Andrew D. Cui, Libin Beyer, Richard P. Easley, Courtney N. Smith, Annette C. Krainc, Dimitri Luquet, Serge Sweet, Ian R. Schwartz, Michael W. La Spada, Albert R. TI Thermoregulatory and metabolic defects in Huntington's disease transgenic mice implicate PGC-1 alpha in Huntington's disease neurodegeneration SO CELL METABOLISM LA English DT Article ID MOUSE MODEL; ENERGY-METABOLISM; CAG REPEAT; ADAPTIVE THERMOGENESIS; MUTANT HUNTINGTIN; GENE-EXPRESSION; DEGENERATION; PROTEIN; ACID; COACTIVATOR AB Huntington's disease (HD) is a fatal, dominantly inherited disorder caused by polyglutarnine repeat expansion in the huntingtin (htt) gene. Here, we observe that HID mice develop hypothermia associated with impaired activation of brown adipose tissue (BAT). Although sympathetic stimulation of PPARy coactivator 1 alpha (PGC-1 alpha) was intact in BAT of HD mice, uncoupling protein 1 (LICP-1) induction was blunted. In cultured cells, expression of mutant htt suppressed UCP-1 promoter activity; this was reversed by PGC-1 alpha expression. HID mice showed reduced food intake and increased energy expenditure, with dysfunctional BAT mitochondria. PGC-1 alpha is a known regulator of mitochondrial function; here, we document reduced expression of PGC-1 a target genes in HD patient and mouse striatum. Mitochondria of HD mouse brain show reduced oxygen consumption rates. Finally, HID striatal neurons expressing exogenous PGC-1 alpha were resistant to 3-nitropropionic acid treatment. Altered PGC-1 alpha function may thus link transcription dysregulation and mitochondrial dysfunction in HID. C1 Univ Washington, Ctr Neurogenet & Neurotherapeut, Dept Lab Med, Seattle, WA 98195 USA. Univ Washington, Ctr Neurogenet & Neurotherapeut, Dept Comparat Med, Seattle, WA 98195 USA. Univ Washington, Ctr Neurogenet & Neurotherapeut, Dept Biochem, Seattle, WA 98195 USA. Univ Washington, Ctr Neurogenet & Neurotherapeut, Dept Neurol, Seattle, WA 98195 USA. Univ Washington, Ctr Ecogenet & Environm Hlth, Seattle, WA 98195 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02129 USA. RP La Spada, AR (reprint author), Univ Washington, Ctr Neurogenet & Neurotherapeut, Dept Lab Med, Seattle, WA 98195 USA. EM laspada@u.washington.edu RI Schwartz, Michael/H-9950-2012; OI luquet, serge/0000-0001-8668-6645 FU NIA NIH HHS [AG00057]; NIDDK NIH HHS [DK063986, DK17047]; NINDS NIH HHS [NS050352] NR 58 TC 332 Z9 335 U1 1 U2 9 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1550-4131 J9 CELL METAB JI Cell Metab. PD NOV PY 2006 VL 4 IS 5 BP 349 EP 362 DI 10.1016/j.cmet.2006.10.004 PG 14 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 103JU UT WOS:000241882300006 PM 17055784 ER PT J AU Choudhury, GG Mahimainathan, L Das, F Venkatesan, B Ghosh-Choudhury, N AF Choudhury, Goutam Ghosh Mahimainathan, Lenin Das, Falguni Venkatesan, Balachandar Ghosh-Choudhury, Nandini TI C-Src couples PI 3 kinase/Akt and MAPK signaling to PDGF-induced DNA synthesis in mesangial cells SO CELLULAR SIGNALLING LA English DT Article DE PDGF; DNA synthesis; c-fos; pRb; CDK2 ID ACTIVATED PROTEIN-KINASE; GROWTH-FACTOR-BETA; CYCLIN-DEPENDENT KINASES; FAMILY TYROSINE KINASES; FACTOR-ALPHA RECEPTOR; PHOSPHATIDYLINOSITOL 3-KINASE; RETINOBLASTOMA PROTEIN; CDK INHIBITOR; PROLIFERATIVE GLOMERULONEPHRITIS; PHOSPHORYLATION SITE AB Platelet-derived growth factor BB (PDGF) and PDGF receptor-beta (PDGFR) play critical roles in mesangial cell proliferation during embryonic development and in mesangioproliferative glomerulonephritis. We have shown previously that phosphatidylinositol (PI) 3 kinase/Akt and Erk1/2 mitogen-activated protein kinase (MAPK) contribute to PDGF-dependent proliferation of mesangial cells, but the mechanism by which these two enzyme cascades are activated by PDGFR signaling is not precisely known. We examined the role of c-Src tyrosine kinase in this process. PDGF increased phosphorylation of c-Src in a time-dependent manner indicating its activation. A pharmacologic inhibitor of c-Src, PP1, blocked PDGF-induced DNA synthesis with concomitant inhibition of c-Src phosphorylation. Inummecomplex kinase assays of c-Src and PDGFR demonstrated inhibition of c-Src tyrosine kinase activity by PP1, without an effect on PDGFR tyrosine phosphorylation. Both PPI and expression of dominant negative c-Src inhibited PDGF-induced PI 3 kinase, resulting in attenuation of Akt kinase activity. Expression of constitutively active c-Src increased Akt activity to the same extent as with PDGF. Constitutively active c-Src augmented PDGF-induced Akt activity, thus contributing to Akt signaling. Inhibition of c-Src tyrosine kinase blocked PDGF-stimulated MAPK activity and resulted in attenuation of c-fos gene transcription with concomitant prevention of Elk-1 transactivation. Furthermore, inhibition of c-Src increased p27(Kip1) cyclin kinase inhibitor, and attenuated PDGF-induced pRb phosphorylation and CDK2 activity. These data provide the first evidence in mesangial cells that PDGF-activated c-Src tyrosine kinase relays signals to PI 3 kinase/Akt and MAPK. Furthermore our results demonstrate that c-Src integrates signals into the nucleus to activate CDK2, which is required for DNA synthesis. (c) 2006 Elsevier Inc. All rights reserved. C1 Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78229 USA. Ctr Geriatr Res Educ & Clin, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, San Antonio, TX USA. RP Choudhury, GG (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM choudhuryg@uthscsa.edu OI /0000-0001-5077-3552 FU NIAMS NIH HHS [R01 AR 5242]; NIDDK NIH HHS [R01 DK 50190, R01 DK 55815] NR 79 TC 40 Z9 41 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0898-6568 J9 CELL SIGNAL JI Cell. Signal. PD NOV PY 2006 VL 18 IS 11 BP 1854 EP 1864 DI 10.1016/j.cellsig.2006.02.003 PG 11 WC Cell Biology SC Cell Biology GA 101DA UT WOS:000241717900004 PM 16530387 ER PT J AU Pan, SF Mi, YA Pally, C Beerli, C Chen, A Guerini, D Hinterding, K Nuesslein-Hildesheim, B Tuntland, T Lefebvre, S Liu, Y Gao, WQ Chu, AA Brinkmann, V Bruns, C Streiff, M Cannet, C Cooke, N Gray, N AF Pan, Shifeng Mi, Yuan Pally, Charles Beerli, Christian Chen, Alice Guerini, Danilo Hinterding, Klaus Nuesslein-Hildesheim, Barbara Tuntland, Tove Lefebvre, Sophie Liu, Yi Gao, Wenqi Chu, Alan Brinkmann, Volker Bruns, Christian Streiff, Markus Cannet, Catherine Cooke, Nigel Gray, Nathanael TI A monoselective sphingosine-1-phosphate receptor-1 agonist prevents allograft rejection in a stringent rat heart transplantation model SO CHEMISTRY & BIOLOGY LA English DT Article ID SPHINGOSINE 1-PHOSPHATE RECEPTOR; PROTEIN-COUPLED RECEPTOR; LYMPHOCYTE EGRESS; S1P(1) RECEPTOR; T-CELLS; FTY720; IMMUNOMODULATOR; IMMUNOSUPPRESSION; SELECTIVITY; MATURATION AB FTY720 is an immunomodulator with demonstrated efficacy in a phase 11 trial of relapsing multiple sclerosis. FTY720-phosphate, the active metabolite generated upon phosphorylation in vivo, acts as a potent agonist on four of the five known sphingosine-1-phosphate (SIP,) receptors. AUY954, an aminocarboxylate analog of FTY720, is a low nanomolar, monoselective agonist of the SIP, receptor. Due to its selectivity and pharmacokinetic profile, AUY954 is an excellent pharmacological probe of S1P(1)-dependent phenomena. Oral administration of AUY954 induces a profound and reversible. reduction of circulating lymphocytes and, in combination with RAD001 (Certican/Everolimus, an mTOR inhibitor), is capable of prolonging the survival of cardiac allografts in a stringent rat transplantation model. This demonstrates that a selective agonist of the S1P(1) receptor is sufficient to achieve efficacy in an animal model of transplantation. C1 Novartis Res Fdn, Genom Inst, San Diego, CA 92121 USA. Novartis Pharma AG, CH-4000 Basel, Switzerland. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. RP Gray, N (reprint author), Novartis Res Fdn, Genom Inst, 10675 John Jay Hopkins Dr, San Diego, CA 92121 USA. EM nathanael_gray@dfci.harvard.edu OI Tuntland, Tove/0000-0001-5831-1723 NR 37 TC 83 Z9 88 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-5521 J9 CHEM BIOL JI Chem. Biol. PD NOV PY 2006 VL 13 IS 11 BP 1227 EP 1234 DI 10.1016/j.chembiol.2006.09.017 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 110YX UT WOS:000242418400014 PM 17114004 ER PT J AU Crothers, K Butt, AA Gibert, CL Rodriguez-Barradas, MC Crystal, S Justice, AC AF Crothers, Kristina Butt, Adeel A. Gibert, Cynthia L. Rodriguez-Barradas, Maria C. Crystal, Stephen Justice, Amy C. CA Veterans Aging Cohort 5 TI Increased COPD among HIV-positive compared to HIV-negative veterans SO CHEST LA English DT Article DE AIDS; HIV infection; obstructive lung diseases; smoking ID OBSTRUCTIVE PULMONARY-DISEASE; QUALITY-OF-LIFE; UNITED-STATES; LUNG-DISEASE; PNEUMOCYSTIS COLONIZATION; ALCOHOL-CONSUMPTION; ADMINISTRATIVE DATA; AIRWAY-OBSTRUCTION; SMOKING-CESSATION; CIGARETTE-SMOKING AB Background: Limited data prior to highly active antiretroviral therapy (HAART) suggested the possibility of an increased risk of COPD among those persons with HIV infection. We sought to determine whether HIV infection is associated with increased prevalence of COPD in the era of HAART. Methods: Prospective observational study of 1,014 HIV-positive and 713 HIV-negative men who were enrolled in the Veterans Aging Cohort 5 Site Study. COPD was determined by patient self-report and International Classification of Diseases, ninth revision (ICD-9), diagnostic codes. Cigarette smoking and injection drug use (IDU) were determined by self-report, and alcohol abuse was determined by ICD-9 diagnostic codes. Laboratory and pharmacy data were obtained from electronic medical records. Results: The prevalence of COPD as determined by ICD-9 codes was 10% in HIV-positive subjects and 9% in HIV-negative subjects (p = 0.4), and as determined by patient self-report was 15% and 12%, respectively (p = 0.04). After adjusting for age, race/ethnicity, pack-years of smoking, IDU, and alcohol abuse, HIV infection was an independent risk factor for COPD. HIV-infected subjects were approximately 50 to 60% more likely to have COPD than HIV-negative subjects (by ICD-9 codes: odds ratio [OR], 1.47; 95% confidence interval [CI], 1.01 to 2.13; p = 0.04; by patient self-report: OR, 1.58; 95% CI, 1.14 to 2.18; p = 0.005). Conclusions: HIV infection was an independent risk factor for COPD, when determined either by ICD-9 codes or patient self-report. Health-care providers should be aware of the increased likelihood of COPD among their HIV-positive patients. The possibility that HIV infection increases susceptibility to and/or accelerates COPD deserves further investigation and has implications regarding the pathogenesis of COPD. C1 VA Connecticut Healthcare Syst, Dept Internal Med, West Haven, CT 06516 USA. Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA. Univ Pittsburgh, Sch Med, Dept Internal Med, Pittsburgh, PA USA. George Washington Univ, Dept Med, Washington, DC USA. Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. Rutgers State Univ, Ctr Pharmacotherapy Chron Dis Management & Outcom, New Brunswick, NJ 08903 USA. RP Justice, AC (reprint author), VA Connecticut Healthcare Syst, Dept Internal Med, 950 Campbell Ave,Mailstop 11-ACSLG, West Haven, CT 06516 USA. EM amy.justice2@va.gov OI Crothers, Kristina/0000-0001-9702-0371 FU NCRR NIH HHS [K12 RR0117594-01]; NIA NIH HHS [K23 AG00826]; NIAAA NIH HHS [3U01 AA 13566] NR 47 TC 145 Z9 148 U1 2 U2 6 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD NOV PY 2006 VL 130 IS 5 BP 1326 EP 1333 DI 10.1378/chest.130.5.1326 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 106OH UT WOS:000242109800010 PM 17099007 ER PT J AU Judge, EP Dodd, JD Masterson, JB Gallagher, CG AF Judge, Eoin P. Dodd, Jonathan D. Masterson, James B. Gallagher, Charles G. TI Pulmonary abnormalities on high-resolution CT demonstrate more rapid decline than FEV1 in adults with cystic fibrosis SO CHEST LA English DT Article DE cystic fibrosis; high-resolution CT; longitudinal study; respiratory function tests ID THIN-SECTION CT; COMPUTED-TOMOGRAPHY; LUNG-DISEASE; SCORING SYSTEMS; FUNCTION TESTS; CHILDREN; TRANSPLANTATION; MORTALITY; CHEST AB Background: FEV1 may remain stable while high-resolution CT (HRCT) appearances deteriorate in children with cystic fibrosis (CF). However, spirometry results commonly decline in older age groups. Objectives: To compare the rate of decline in HRCT abnormalities and spirometry results over time in an adult cohort with CF. Methods: The HRCT scans of 39 consecutive patients (19 males and 20 females; mean age, 22 years; range, 16 to 48 years) with two HRCT scans > 18 months apart were randomly and blindly scored using a modified Bhalla scoring system by two independent chest radiologists. Age, body mass index, spirometry, and sputum cultures were recorded at the time of both HRCTs. Rates of change in clinical parameters and HRCT abnormalities were calculated and compared using repeated-measures analysis of variance. Results: Mean FEV1 declined at a rate of -2.3% per year, while mean HRCT total score declined at a rate of -2.7% per year. Several individual HRCT abnormalities as well as HRCT total scores declined significantly faster than FEV1 (p < 0.001). Six patients showed stable spirometry results but worsening HRCT scores. Mucus plugging and extent of bronchiectasis deteriorated at a more rapid rate in the group with mildly impaired lung function. Air trapping, collapse/consolidation, peribronchial thickening, severity of bronchiectasis, and generations of bronchial divisions involved deteriorated at a more rapid rate in the group with moderate-to-severely impaired lung function. Conclusions: Adult CF patients have more rapid rates of decline in HRCT abnormalities than in spirometry results. Individual HRCT abnormalities decline at different rates depending on the degree of lung function impairment. C1 St Vincent Univ Hosp, Dept Resp Med, Dublin, Ireland. St Vincent Univ Hosp, Dept Radiol, Dublin, Ireland. RP Dodd, JD (reprint author), Massachusetts Gen Hosp, CIMIT Off, Suite 400,Charles River Pl,Cambridge St, Boston, MA 02114 USA. EM jddodd@partners.org NR 35 TC 42 Z9 43 U1 0 U2 1 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD NOV PY 2006 VL 130 IS 5 BP 1424 EP 1432 DI 10.1378/chest.130.5.1424 PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 106OH UT WOS:000242109800023 PM 17099020 ER PT J AU Steiner, MK Preston, IR Klinger, JR Criner, GJ Waxman, AB Farber, HW Hill, NS AF Steiner, M. Kathryn Preston, Ioana R. Klinger, James R. Criner, Gerard J. Waxman, Aaron B. Farber, Harrison W. Hill, Nicholas S. TI Conversion to bosentan from prostacyclin infusion therapy in pulmonary arterial hypertension - A pilot study SO CHEST LA English DT Article DE bosentan; epoprostenol; pulmonary arterial hypertension; transitions; treprostinil ID CONTINUOUS INTRAVENOUS EPOPROSTENOL; 6-MINUTE WALK TEST; TREPROSTINIL; ECHOCARDIOGRAPHY; TRANSITION; EXPRESSION; SYNTHASE; LUNGS AB Study objectives: We assessed the efficacy of bosentan in transitioning from prostacyclin infusions in patients with pulmonary arterial hypertension (PAH). Methods: Twenty-two PAH patients were recruited from five PAH centers if they had been clinically stable while receiving therapy with IV epoprostenol or subcutaneous treprostinil for at least 3 months. Patients were observed in an open-label prospective trial while bosentan was added to therapy, and then epoprostenol or treprostinil were tapered after 2 months. Results: Ten of the 22 patients were transitioned off prostacyclin infusion therapy after a mean (+/- SEM) duration of 6.1 +/- 1.2 months. Of those patients, seven patients have continued not receiving prostacyclin infusion therapy for a mean duration of 17.7 +/- 5.3 months, with no significant changes in pulmonary artery (PA) pressure estimated by echocardiography, World Health Organization (WHO)/New York Heart Association (NYHA) functional class, 6-min walk distance (6MWD), or Borg dyspnea score. The conditions of three patients deteriorated, necessitating the resumption of prostacyclin therapy, and two patients subsequently died. Twelve patients failed to transition or even lower the prostacylin infusion rate and had worsening of their WHO/NYHA functional class and estimated systolic PA pressures, and had a trend toward deterioration in their mean 6MWD (294 +/- 41 to 198 +/- 34 m, respectively; p = 0.2). Of these, two patients subsequently died. The baseline characteristics of those who transitioned successfully vs those who transitioned unsuccessfully were a lower prostacyclin infusion rate, and less severe elevations in the mean and estimated systolic PA pressures. Conclusion: Transitioning from therapy with prostacyclin to bosentan is possible in some PAH patients, mainly in those receiving lower prostacyclin doses and having less pulmonary hypertension at baseline. Careful patient selection and close interim monitoring is needed because the conditions of patients can deteriorate, and they may not respond to the resumption of therapy with prostacyclin. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Boston Med Ctr, Boston, MA USA. Temple Univ Hosp & Med Sch, Philadelphia, PA 19140 USA. Rhode Isl Hosp, Providence, RI USA. Tufts Univ, New England Med Ctr, Boston, MA 02111 USA. RP Steiner, MK (reprint author), Massachusetts Gen Hosp, 55 Fruit St,Bulfinch Bldg 148, Boston, MA 02114 USA. EM ksteiner@partners.org OI Farber, Harrison/0000-0002-0297-7902 NR 19 TC 19 Z9 20 U1 0 U2 2 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD NOV PY 2006 VL 130 IS 5 BP 1471 EP 1480 DI 10.1378/chest.130.5.1471 PG 10 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 106OH UT WOS:000242109800029 PM 17099026 ER PT J AU Darabi, K Abdel-Wahab, O Stowell, C Sepehr, A AF Darabi, Kamran Abdel-Wahab, Omar Stowell, Chtistopher Sepehr, Alireza TI Pulmonary and critical care pearls - An 87-year-old woman with respiratory distress and alveolar hemorrhage after transfusion - Transfusion-related acute lung injury complicated by alveolar hemorrhage SO CHEST LA English DT Editorial Material C1 Our Lady Mercy Med Ctr, Ctr Canc, Div Hematol & Med Oncol, Bronx, NY 10466 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Darabi, K (reprint author), Our Lady Mercy Med Ctr, Ctr Canc, Div Hematol & Med Oncol, 600 E 233rd St, Bronx, NY 10466 USA. EM kamrandarabi@yahoo.com NR 9 TC 4 Z9 4 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 NOV PY 2006 VL 130 IS 5 BP 1612 EP 1616 DI 10.1378/chest.130.5.1612 PG 5 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 106OH UT WOS:000242109800048 PM 17099045 ER PT J AU Hosokawa, I Hosokawa, Y Komatsuzawa, H Goncalves, RB Karimbux, N Napimoga, MH Seki, M Ouhara, K Sugai, M Taubman, MA Kawai, T AF Hosokawa, I. Hosokawa, Y. Komatsuzawa, H. Goncalves, R. B. Karimbux, N. Napimoga, M. H. Seki, M. Ouhara, K. Sugai, M. Taubman, M. A. Kawai, T. TI Innate immune peptide LL-37 displays distinct expression pattern from beta-defensins in inflamed gingival tissue SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Article DE ELISA; epithelial cells; neutrophils; periodontal; oral immunology ID EPITHELIAL-CELLS; ACTINOBACILLUS-ACTINOMYCETEMCOMITANS; PORPHYROMONAS-GINGIVALIS; ANTIMICROBIAL PEPTIDES; HUMAN KERATINOCYTES; ANTIBACTERIAL PEPTIDES; HUMAN BETA-DEFENSIN-1; PERIODONTAL-DISEASE; BACTERIA; GENE AB Anti-microbial peptides produced from mucosal epithelium appear to play pivotal roles in the host innate immune defence system in the oral cavity. In particular, human beta-defensins (hBDs) and the cathelicidin-type antimicrobial peptide, LL-37, were reported to kill periodontal disease-associated bacteria. In contrast to well-studied hBDs, little is known about the expression profiles of LL-37 in gingival tissue. In this study, the anti-microbial peptides expressed in gingival tissue were analysed using immunohistochemistry and enxyme-linked immunosorbent assay (ELISA). Immunohistochemistry revealed that neutrophils expressed only LL-37, but not hBD-2 or hBD-3, and that such expression was prominent in the inflammatory lesions when compared to healthy gingivae which showed very few or no LL-37 expressing neutrophils. Gingival epithelial cells (GEC), however, expressed all three examined anti-microbial peptides, irrespective of the presence or absence of inflammation. Moreover, as determined by ELISA, the concentration of LL-37 in the gingival tissue homogenates determined was correlated positively with the depth of the gingival crevice. Stimulation with periodontal bacteria in vitro induced both hBD-2 and LL-37 expressions by GEC, whereas peripheral blood neutrophils produced only LL-37 production, but not hBD-2, in response to the bacterial stimulation. These findings suggest that LL-37 displays distinct expression patterns from those of hBDs in gingival tissue. C1 Forsyth Inst, Dept Immunol, Boston, MA 02115 USA. Hiroshima Univ, Grad Sch Biomed Sci, Dept Bacteriol, Hiroshima, Japan. Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. Mitsubishi Pharma Corp, Div Res & Dev, Tokyo, Japan. RP Kawai, T (reprint author), Forsyth Inst, Dept Immunol, 140 The Fenway, Boston, MA 02115 USA. EM tkawai@forsyth.org RI Napimoga, Marcelo/F-8789-2011 OI Napimoga, Marcelo/0000-0003-4472-365X FU NIDCR NIH HHS [DE-14551, R01 DE003420, DE-03420, K22 DE014551, R37 DE003420] NR 36 TC 61 Z9 62 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0009-9104 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD NOV PY 2006 VL 146 IS 2 BP 218 EP 225 DI 10.1111/j.1365-2249.2006.03200.x PG 8 WC Immunology SC Immunology GA 093XJ UT WOS:000241203300005 PM 17034573 ER PT J AU Almawi, WY Wakim-Ghorayeb, SF Arekat, MR Najm, P Keleshian, SH Al-Sayed, N Blanchon, B Sarnaha, HR Irani-Hakime, N AF Almawi, Wassim Y. Wakim-Ghorayeb, Saria F. Arekat, Mona R. Najm, Pierre Keleshian, Sose H. Al-Sayed, Nasreen Blanchon, Bruno Sarnaha, Hanady R. Irani-Hakime, Noha TI Association of selective HLA class II susceptibility-conferring and protective haplotypes with type 2 diabetes in patients from Bahrain and Lebanon SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID MELLITUS; ALLELES; HETEROGENEITY; AUTOIMMUNITY; PREVALENCE; HLA-DRB1; DISEASE; MARKERS; ARABS; DRB1 AB The association of HLA class II with type 2 diabetes (T2DM) was investigated in Bahraini and Lebanese subjects. DRB1*070101 (Lebanese and Bahraini) and DQB1*0201 (Lebanese) were susceptibility-conferring alleles, and unique susceptibility-conferring/protective haplotypes were found in both patient groups. Regression analysis confirmed that DRB1*070101-DQB1*0201 (Bahraini) and DRB1*110101-DQB1*0201 (Lebanese) were susceptibility-conferring haplotypes. C1 Arabian Gulf Univ, Coll Med & Med Sci, Dept Biochem Med, Manama, Bahrain. Joslin Diabet Ctr, Manama, Bahrain. St Georges Univ Hosp, Beirut, Lebanon. Haigazian Univ, Beirut, Lebanon. RP Almawi, WY (reprint author), Arabian Gulf Univ, Coll Med & Med Sci, Dept Biochem Med, POB 22979, Manama, Bahrain. EM wyalmawi@yahoo.co.uk NR 20 TC 7 Z9 7 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1556-6811 J9 CLIN VACCINE IMMUNOL JI Clin. Vaccine Immunol. PD NOV PY 2006 VL 13 IS 11 BP 1296 EP 1298 DI 10.1128/CVI.00206-06 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 107EC UT WOS:000242152500018 PM 16988007 ER PT J AU Khwaja, FW Duke-Cohan, JS Brat, DJ Meir, EG AF Khwaja, Fatima W. Duke-Cohan, Jonathan S. Brat, Daniel J. Van Meir, Erwin G. TI Attractin is elevated in the cerebrospinal fluid of patients with malignant astrocytoma and mediates glioma cell migration SO CLINICAL CANCER RESEARCH LA English DT Article ID CUB-FAMILY; DPPT-L; PROTEINS; PROTEOMICS; SAMPLES; BLOOD; LINES AB Purpose: There are a limited number of noninvasive methods available for the monitoring of neoplastic disease in the central nervous system. The goal of our study was to find reliable markers that could be used for disease monitoring as well as to identify new targets for the therapeutic intervention for malignant astrocytoma (WHO grades 3 and 4). Experimental Design: We employed proteomic techniques to identify secreted proteins in the cerebrospinal fluid that were specific to patients with malignant astrocytoma. Results: Among 60 cerebrospinal fluid samples of patients with various central nervous system diseases, attractin was consistently found to be elevated in the samples of patients with malignant astrocytoma. To independently validate these results, we examined attractin expression in a new set of 108 normal and tumoral brain tissue specimens and found elevated expression in 97% of malignant astrocytomas, with the highest levels in grade 4 tumors. Using immunohistochemistry, we further showed that attractin is produced and secreted by. the tumor cells. Finally, we showed that cerebrospinal fluid from brain tumor patients induces glioma cell migration and that attractin is largely responsible for this promigratory activity. Conclusions: Our results find attractin to be a reliable secreted marker for high-grade gliomas. Additionally, our migration studies suggest that it may be an important mediator of tumor invasiveness, and thus, a potential target in future therapies. C1 Emory Univ, Sch Med, Winship Canc Inst, Dept Neurosurg,Lab Mol Neurooncol, Atlanta, GA 30322 USA. Emory Univ, Sch Med, Winship Canc Inst, Dept Hematol Oncol,Lab Mol Neurooncol, Atlanta, GA 30322 USA. Emory Univ, Sch Med, Dept Pathol & Lab Med, Atlanta, GA 30322 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. RP Meir, EG (reprint author), Emory Univ, Sch Med, Winship Canc Inst, Dept Neurosurg,Lab Mol Neurooncol, 1365C Clifton Rd NE,C5078, Atlanta, GA 30322 USA. EM evanmei@emory.edu OI Duke-Cohan, Jonathan/0000-0002-9478-9609; Van Meir, Erwin G./0000-0003-2444-7707 FU NCI NIH HHS [CA 86335] NR 22 TC 22 Z9 23 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV 1 PY 2006 VL 12 IS 21 BP 6331 EP 6336 DI 10.1158/1078-0432.CCR-06-1296 PG 6 WC Oncology SC Oncology GA 104DB UT WOS:000241935100004 PM 17085642 ER PT J AU Weisbord, SD Bernardini, J Mor, MK Hartwig, KC Nicoletta, PJ Palevsky, PM Piraino, B AF Weisbord, Steven D. Bernardini, Judith Mor, Maria K. Hartwig, Kathryn C. Nicoletta, Patricia J. Palevsky, Paul M. Piraino, Beth TI The effect of coronary angiography on residual renal function in patients on peritoneal dialysis SO CLINICAL CARDIOLOGY LA English DT Article DE coronary angiography; residual renal function; peritoneal dialysis ID MORTALITY; DECLINE; CLEARANCES; RATES; CAPD AB Background: The risk of intravascular radiocontrast to residual renal function (RRF) in patients on peritoneal dialysis (PD) remains largely unknown. Hypothesis: This study sought to estimate the effect of coronary angiography on RRF in patients on PD. Methods: All patients at the VA Pittsburgh Healthcare System and University of Pittsburgh who underwent coronary angiography between 1993 and 2005 while on PD and who had RRF measured prior to angiography were identified retrospectively. For patients without a postprocedure RRF recorded, medical records were reviewed to determine whether anuria had developed. The longer-term rate of loss of RRF among cases was compared with a composite rate of decline in RRF among cases before angiography and matched controls. Results: Twenty-nine patients with a mean preprocedure RRF of 4.4 +/- 3.2 ml/min/1.73m(2) were evaluated. Of these patients, 23 (79%) had postangiography RRF assessments (mean clearance 3.4 +/- 3.0 ml/min/1.73m(2)). One of the remaining six patients definitely became permanently anuric following angiography, one was lost to follow-up, and there was no postprocedure RRF assessment in four others. The rate of decline in RRF in the cases was similar to the composite rate (0.07 ml/min/1.73m(2)/month vs. 0.09 ml/min/1.73m(2)/Month, p = 0.53) Conclusion: The risk for permanent anuria in patients on PD undergoing coronary angiography appears to be quite small. Patients who do not develop anuria following coronary angiography have the same gradual rate of loss of RRF as other patients on PD. Providers should be vigilant in protecting RRF in patients on PD undergoing coronary angiography. C1 VA Pittsburgh Healthcare Syst, Renal Sect, Med Special Serv Line, Pittsburgh, PA 15240 USA. VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA 15240 USA. Univ Pittsburgh, Sch Med, Renal Electrolyte Div, Dept Med, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA. RP Weisbord, SD (reprint author), VA Pittsburgh Healthcare Syst, Renal Sect, Med Special Serv Line, Mailstop 111F-U,7E rm120, Pittsburgh, PA 15240 USA. EM weisbordsd@upmc.edu OI Piraino, Beth/0000-0001-5061-0841; Palevsky, Paul/0000-0002-7334-5400 NR 15 TC 12 Z9 12 U1 0 U2 0 PU CLINICAL CARDIOLOGY PUBL CO PI MAHWAH PA PO BOX 832, MAHWAH, NJ 07430-0832 USA SN 0160-9289 J9 CLIN CARDIOL JI Clin. Cardiol. PD NOV PY 2006 VL 29 IS 11 BP 494 EP 497 DI 10.1002/clc.4960291105 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 100AF UT WOS:000241638700004 PM 17133846 ER PT J AU Gupta, S Vittinghoff, E Bertenthal, D Corley, D Shen, H Walter, LC McQuaid, K AF Gupta, Samir Vittinghoff, Eric Bertenthal, Daniel Corley, Douglas Shen, Hui Walter, Louise C. McQuaid, Kenneth TI New-onset diabetes and pancreatic cancer SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article ID UNITED-STATES ADULTS; GLUCOSE-METABOLISM; SUBTOTAL PANCREATECTOMY; MELLITUS; RISK; COHORT; MORTALITY; CARCINOMA; METAANALYSIS; PROBABILITY AB Background & Aims: Although many individuals with pancreatic cancer have diabetes, the association between new-onset diabetes mellitus and the subsequent incidence of pancreatic cancer is unclear. Methods: We conducted a retrospective cohort study to estimate the incidence of pancreatic cancer subsequent to a new diabetes diagnosis and to evaluate factors associated with a subsequent pancreatic cancer diagnosis. We used the Veterans Health Administration National Patient Care Database to assemble a cohort of 1,421,794 US veterans without prior diabetes or pancreatic cancer diagnoses. We recorded coding for new diabetes diagnoses (>= 2 International Classification of Diseases-9 codes for diabetes within a 12-month period), pancreatic cancer, age, sex, race, and common gastrointestinal symptoms. Results: A total of 36,631 (2.6%) of the 1,421,794 veterans were diagnosed with new-onset diabetes in 1999, 149 subsequently received a diagnosis of pancreatic cancer. Pancreatic cancer incidence in patients with new-onset diabetes (83.8/100,000 person-years) was 2.2-fold higher (95% confidence interval, 1.84-2.56) than in nondiabetics, and was highest during the first 2 years after diabetes diagnosis. One additional pancreatic cancer was diagnosed for every 332 new diabetics over 6 years. A subsequent pancreatic cancer diagnosis (among new-onset diabetics) was associated independently with younger age groups, changes in bowel habits, constipation, epigastric pain, and malnutrition. Conclusions: New-onset diabetes was associated with a significantly increased rate of pancreatic cancer diagnosis, particularly in the first 2 years after diabetes diagnosis. Factors associated with pancreatic cancer diagnosis included younger age groups and the presence of gastrointestinal symptoms. The absolute incidence of pancreatic cancer was low. C1 Vet Affairs Med Ctr, GI Sect, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. San Francisco Vet Affairs Med Ctr, Dept Vet Affairs,Res Enhancement Award Program, Hlth Serv Res & Dev Serv, Interdisciplinary Res Program Improve Care Older, San Francisco, CA USA. Kaiser Permanente Div Res, Oakland, CA USA. RP McQuaid, K (reprint author), Vet Affairs Med Ctr, GI Sect, 111-B-1,4150 Clement St, San Francisco, CA 94121 USA. EM kenneth.mcquaid@med.va.gov NR 42 TC 40 Z9 46 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD NOV PY 2006 VL 4 IS 11 BP 1366 EP 1372 DI 10.1016/j.cgh.2006.06.024 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 108UD UT WOS:000242263800015 PM 16945591 ER PT J AU Wormser, GP Dattwyler, RJ Shapiro, ED Halperin, JJ Steere, AC Klempner, MS Krause, PJ Bakken, JS Strle, F Stanek, G Bockenstedt, L Fish, D Dumler, JS Nadelman, RB AF Wormser, Gary P. Dattwyler, Raymond J. Shapiro, Eugene D. Halperin, John J. Steere, Allen C. Klempner, Mark S. Krause, Peter J. Bakken, Johan S. Strle, Franc Stanek, Gerold Bockenstedt, Linda Fish, Durland Dumler, J. Stephen Nadelman, Robert B. TI The clinical assessment, treatment, and prevention of Lyme disease, human granulocytic anaplasmosis, and babesiosis: Clinical practice guidelines by the infectious diseases society of America SO CLINICAL INFECTIOUS DISEASES LA English DT Review ID ACRODERMATITIS-CHRONICA-ATROPHICANS; BORRELIA-BURGDORFERI DNA; IN-VITRO SUSCEPTIBILITY; POLYMERASE CHAIN-REACTION; CENTRAL-NERVOUS-SYSTEM; NEW-YORK-STATE; COST-EFFECTIVENESS ANALYSIS; CONFIRMED ERYTHEMA MIGRANS; PLACEBO-CONTROLLED TRIAL; CHRONIC-FATIGUE-SYNDROME AB Evidence-based guidelines for the management of patients with Lyme disease, human granulocytic anaplasmosis (formerly known as human granulocytic ehrlichiosis), and babesiosis were prepared by an expert panel of the Infectious Diseases Society of America. These updated guidelines replace the previous treatment guidelines published in 2000 (Clin Infect Dis 2000; 31[Suppl 1]:1-14). The guidelines are intended for use by health care providers who care for patients who either have these infections or may be at risk for them. For each of these Ixodes tickborne infections, information is provided about prevention, epidemiology, clinical manifestations, diagnosis, and treatment. Tables list the doses and durations of antimicrobial therapy recommended for treatment and prevention of Lyme disease and provide a partial list of therapies to be avoided. A definition of post-Lyme disease syndrome is proposed. C1 New York Med Coll, Div Infect Dis, Dept Med, Valhalla, NY 10595 USA. New York Med Coll, Div Allergy Immunol & Rheumatol, Dept Med, Valhalla, NY 10595 USA. NYU, Sch Med, New York, NY USA. Atlantic Neurosci Inst, Summit, NJ USA. Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06510 USA. Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. Yale Univ, Sch Med, Dept Med, Rheumatol Sect, New Haven, CT 06510 USA. Univ Connecticut, Sch Med, Dept Pediat, Hartford, CT 06112 USA. Connecticut Childrens Med Ctr, Hartford, CT USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Rheumatol Allergy & Immunol, Boston, MA USA. Boston Univ, Med Ctr, Boston, MA USA. Boston Univ, Sch Med, Boston, MA 02118 USA. St Lukes Hosp, Infect Dis Sect, Duluth, MN USA. Johns Hopkins Med Inst, Dept Pathol, Div Med Microbiol, Baltimore, MD 21205 USA. Univ Ljubljana, Med Ctr, Dept Infect Dis, Ljubljana 61000, Slovenia. Med Univ Vienna, Vienna, Austria. RP Wormser, GP (reprint author), New York Med Coll, Div Infect Dis, Dept Med, Rm 245,Munger Pavil, Valhalla, NY 10595 USA. EM Gary_Wormser@nymc.edu NR 403 TC 692 Z9 729 U1 18 U2 98 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD NOV 1 PY 2006 VL 43 IS 9 BP 1089 EP 1134 DI 10.1086/508667 PG 46 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 092OF UT WOS:000241106500001 PM 17029130 ER PT J AU Micheli, L Curtis, C Shervin, N AF Micheli, Lyle Curtis, Christine Shervin, Nina TI Articular cartilage repair in the adolescent athlete: Is autologous chondrocyte implantation the answer? SO CLINICAL JOURNAL OF SPORT MEDICINE LA English DT Article DE articular; cartilage; repair; adolescent; athlete; ACI ID OSTEOCHONDRITIS-DISSECANS; FOLLOW-UP; NATURAL-HISTORY; KNEE; DEFECTS; MOSAICPLASTY; TRANSPLANTATION; OSTEONECROSIS; PATHOGENESIS; MULTICENTER AB Objective: To determine the evidence base for recommendations regarding autologous chondryocyte implantation in adolescent athletes. Materials and Methods: All literature on articular cartilage repair from MEDLINE search dated 1990 to 2006 was reviewed. The majority of articles describe surgical technique and indications. Three techniques for secondary articular cartilage repair have been identified: autologous chondrocyte implantation, autologous osteochondral implants, and marrow stimulation techniques. The initial literature search identified 4 studies that reported the effectiveness and durability of autologous chondrocyte implantation in adults and 2 studies that reported the outcomes of autologous chondrocyte implantation in adolescent athletes. No results of osteochondral implantation or marrow stimulation techniques in adolescent athletes have been published. Results: Acceptable repair rates with all 3 techniques have been reported in adult athletes. Two studies reported high success using autolgous chondrocyte implantation (ACI) in children. Conclusions: Articular cartilage injury in young athletes remains a difficult problem. The ideal situation is early diagnosis and primary repair, particularly with lesions of the knee, elbow, and ankle. In cases where primary repair is not possible or has been unsuccessful and the lesion is large or symptomatic, secondary repair with either marrow stimulation, microfracture, autologous chondrocyte implantation, or autologous osteochondral grafting may be used. However, at present only the results of ACI repair have been reported for adolescent athletes. C1 Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Micheli, L (reprint author), Div Sports Med, 319 Longwood Ave,2nd Floor, Boston, MA 02115 USA. EM michelilyle@aol.com NR 35 TC 18 Z9 21 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1050-642X J9 CLIN J SPORT MED JI Clin. J. Sport Med. PD NOV PY 2006 VL 16 IS 6 BP 465 EP 470 DI 10.1097/01.jsm.0000248842.93755.e2 PG 6 WC Orthopedics; Physiology; Sport Sciences SC Orthopedics; Physiology; Sport Sciences GA 111AW UT WOS:000242424000003 PM 17119359 ER PT J AU Harmon, W Delmonico, F AF Harmon, William Delmonico, Francis TI Payment for kidneys: A government-regulated system is not ethically achievable SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Delmonico, F (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM francis_delmonico@neob.org NR 0 TC 13 Z9 13 U1 0 U2 0 PU AMERICAN SOCIETY NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD NOV PY 2006 VL 1 IS 6 BP 1146 EP 1147 DI 10.2215/CJN.03050906 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 107CK UT WOS:000242148100004 PM 17699339 ER PT J AU Aslam, N Bernardini, J Fried, L Burr, R Piraino, B AF Aslam, Nabeel Bernardini, Judith Fried, Linda Burr, Renee Piraino, Beth TI Comparison of infectious complications between incident hemodialysis and peritoneal dialysis patients SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article; Proceedings Paper CT 38th Annual Meeting of the American-Society-of-Nephrology CY NOV 08-13, 2005 CL Philadelphia, PA SP Amer Soc Nephrol ID VASCULAR ACCESS; UNITED-STATES; RISK-FACTORS; SEPTICEMIA; MORTALITY; MULTICENTER; POPULATION; PREVENTION; BACTEREMIA; OUTCOMES AB The impact of dialysis modality on infection, especially early in the course of dialysis, has not been well studied. This study compared infection between hemodialysis (HD) and peritoneal dialysis (PD) from the start of dialysis and evaluated factors that have an impact on infection risk. In this observational cohort study, all incident dialysis patients (n = 181; HD 119 and PD 62) at a single center from 1999 to 2005 had data collected prospectively beginning day 1 of dialysis. Excluded were those with any previous ESRD therapy. Infection rates were evaluated using multivariate Poisson regression. Overall infection rates were similar (HD 0.77 versus PD 0.86/yr; P = 0.24). Only HD patients had bacteremia (0.16/yr), and only PD patients had peritonitis (0.24/yr). Bacteremia that occurred :590 d after start of HD was 0.44/yr, increased compared with overall rate of 0.16/yr (P < 0.004). HD catheters, used in 67% of patients who started HD, were associated with a strikingly increased rate of bacteremia. Peritonitis <= 90 d was 0.22/yr, no different from the overall rate. Modality was not an independent predictor of overall infections (PD versus HD: relative risk 1.30; 95% confidence interval 0.93 to 1.8; P = 0.12) using multivariate analysis. PD and HD patients had similar infection rates overall, but type of infection and risk over time varied. HD patients had an especially high risk for bacteremia in the first 90 d, whereas the risk for peritonitis for the PD cohort was not different over time. These results support the placement of permanent accesses (fistula or PD catheter) before the start of dialysis to avoid use of HD catheters. C1 Univ Pittsburgh, Sch Med, Dept Med, Div Renal & Electrolyte, Pittsburgh, PA 15260 USA. VA Pittsburgh Hlth Care Syst, Pittsburgh, PA USA. RP Piraino, B (reprint author), 3504 5th Ave,Suite 200, Pittsburgh, PA 15213 USA. EM piraino@pitt.edu OI Piraino, Beth/0000-0001-5061-0841 NR 24 TC 65 Z9 67 U1 0 U2 3 PU AMERICAN SOCIETY NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD NOV PY 2006 VL 1 IS 6 BP 1226 EP 1233 DI 10.2215/CJN.01230406 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 107CK UT WOS:000242148100017 PM 17699352 ER PT J AU Sezer, O Vesole, DH Singhal, S Richardson, P Stadtmauer, E Jakob, C Boral, AL Esseltine, DL Mehta, J AF Sezer, Orhan Vesole, David H. Singhal, Seema Richardson, Paul Stadtmauer, Edward Jakob, Christian Boral, Anthony L. Esseltine, Dixie-Lee Mehta, Jayesh TI Bortezomib-induced tumor lysis syndrome in multiple myeloma SO CLINICAL LYMPHOMA & MYELOMA LA English DT Article DE dexamethasone; hemodialysis; proteasome ID THALIDOMIDE AB Tumor lysis syndrome (TLS) is exceedingly rare in multiple myeloma because of the relatively slow proliferation and response of the malignant cells. Bortezomib is a novel agent that inhibits proteasome and has shown activity against multiple myeloma. We report 8 episodes of TLS seen in 7 patients with bortezomib therapy, with or without dexamethasone, among 496 patients treated on 3 phase II multicenter studies. Biochemical abnormalities resolved with supportive therapy in 6 patients (including hemodialysis in 2) but proved fatal in 1. Clinicians should be alert for TLS in patients with myeloma with significant disease burden treated with bortezomib because of the potential for rapid onset of cell lysis with this agent. C1 Univ Hosp Charite, Dept Hematol & Oncol, Berlin, Germany. St Vincents Comprehens Canc Ctr, New York, NY USA. Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Feinberg Sch Med, Div Hematol Oncol, Chicago, IL 60611 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Penn, Ctr Canc, Hematol Malignancies Program, Philadelphia, PA 19104 USA. Millennium Pharmaceut, Cambridge, MA USA. RP Sezer, O (reprint author), Charite Univ Med Berlin, Dept Hematol & Oncol, D-10117 Berlin, Germany. EM sezer@charite.de NR 15 TC 24 Z9 26 U1 0 U2 0 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1557-9190 J9 CLIN LYMPHOMA MYELOM JI Clin. Lymphoma Myeloma PD NOV PY 2006 VL 7 IS 3 BP 233 EP 235 DI 10.3816/CLM.2006.n.064 PG 3 WC Oncology SC Oncology GA 105OI UT WOS:000242039800010 PM 17229340 ER PT J AU Most, E Sultan, PG Park, SE Papannagari, R Li, G AF Most, Ephrat Sultan, Peter G. Park, Sang Eun Papannagari, Ramprasad Li, Guoan TI Tibiofemoral contact behavior is improved in high-flexion cruciate retaining TKA SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH LA English DT Article; Proceedings Paper CT Open Scientific Meeting of the Knee-Society CY 2007 CL San Diego, CA SP Knee Soc ID TOTAL KNEE ARTHROPLASTY; IN-VITRO; FUNCTIONAL-ACTIVITIES; FLUOROSCOPIC ANALYSIS; FEMORAL ROLLBACK; FIXED-BEARING; DEEP FLEXION; KINEMATICS; MOTION; DESIGN AB Recently, total knee arthroplasty (TKA) designs have been modified to prevent edge loading on the posterior tibial articular surface and increase the tibiofemoral contact area at high degrees of flexion. The expected improvement in contact behavior of high-flexion TKA over conventional design is not well documented. We ascertained peak contact locations and contact areas of a conventional and a high-flexion cruciate-retaining TKA design. Both TKAs showed similar kinematics throughout the range of flexion although their contact behaviors differed: the peak contact point for the high-flexion TKA was located more anteriorly than the conventional TKA for flexion angles greater than 90 degrees. The tibiofemoral contact (of both TKAs reached the polyethylene posterior edge at 150 degrees. The contact on conventional TKA reached the polyethylene posterior edge approximately 15 degrees to 30 degrees before the high-flexion TKA. The high flexion TKA exhibited similar contact areas to conventional TKA. While the clinical relevance is unclear, these data suggest high flexion TKA might improve tibiofemoral contact biomechanics if high flexion is achievable. C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Bioengn Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. MIT, Dept Mech Engn, Cambridge, MA 02139 USA. SterlingTech Software Inc, Tenafly, NJ USA. RP Li, G (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Bioengn Lab, 55 Fruit St,GRJ 1215, Boston, MA 02114 USA. EM gli1@partners.org NR 24 TC 23 Z9 26 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0009-921X EI 1528-1132 J9 CLIN ORTHOP RELAT R JI Clin. Orthop. Rel. Res. PD NOV PY 2006 IS 452 BP 59 EP 64 DI 10.1097/01.blo.0000238843.11176.42 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 119OK UT WOS:000243021400012 PM 16980895 ER PT J AU Hinton, DE AF Hinton, Devon E. TI Special issue - Culturally sensitive CBT SO COGNITIVE AND BEHAVIORAL PRACTICE LA English DT Editorial Material AB The United States is a profoundly multiethnic country. Increasingly, it is realized that the Presentation of psychological distress, and its treatment, is influenced in important ways by culture. The current special issue aims to explore how culture impacts on the treatment Process-from distress presentation to mechanisms generating distress to the manner in which mechanisms generating distress must be addressed. In this Introduction to the special issue, I will summarize the contributions, and give some sense of how they illustrate the importance of culture in the treatment Process. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Hinton, DE (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 15 Parkman St,WACC 812, Boston, MA 02114 USA. EM devon_hinton@hms.harvard.edu NR 12 TC 4 Z9 4 U1 2 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1077-7229 J9 COGN BEHAV PRACT JI Cogn. Behav. Pract. PD NOV PY 2006 VL 13 IS 4 BP 246 EP 248 DI 10.1016/j.cbpra.2006.07.002 PG 3 WC Psychology, Clinical SC Psychology GA 174HY UT WOS:000246934200002 ER PT J AU Hinton, DE Otto, MW AF Hinton, Devon E. Otto, Michael W. TI Symptom presentation and symptom meaning among traumatized Cambodian refugees: Relevance to a somatically focused cognitive-behavior therapy SO COGNITIVE AND BEHAVIORAL PRACTICE LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; TREATMENT-RESISTANT PTSD; ATAQUES-DE-NERVIOS; PANIC-DISORDER; ANXIETY SENSITIVITY; MENTAL-HEALTH; VIETNAMESE REFUGEES; BHUTANESE REFUGEES; MASS VIOLENCE; PUERTO-RICO AB Among psychologically distressed Cambodian refugees, somatic complaints are particularly prominent. Cambodians interpret anxiety-related somatic sensations in terms of "Wind " (khyal), an ethnophysiology that gives rise to multiple catash-ophic interpretations,, and they have prominent trauma-memory associations to anxiety-related somatic symptoms. In this article, we detail some of the common sensation-related dysphoric networks of Cambodian refugees, focusing on catastrophic cognitions and trauma associations. We argue that delineating symptom-related dysphoric networks is crucial to successfully adapt cognitive-behavioral interventions to treat panic disorder and posttraumatic stress disorder among Cambodian refugees, and that such an approach may be useful for the culturally sensitive adaptation of cognitive-behavior therapy for other traumatized non-Western. groups. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Boston Univ, Boston, MA 02215 USA. RP Hinton, DE (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 15 Parkman St,WACC 812, Boston, MA 02114 USA. EM devon_hinton@hms.harvard.edu FU NIMH NIH HHS [K23 MH066253-02, K23 MH066253, R01 MH094312] NR 99 TC 28 Z9 29 U1 5 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1077-7229 J9 COGN BEHAV PRACT JI Cogn. Behav. Pract. PD NOV PY 2006 VL 13 IS 4 BP 249 EP 260 DI 10.1016/j.cbpra.2006.04.006 PG 12 WC Psychology, Clinical SC Psychology GA 174HY UT WOS:000246934200003 PM 19823603 ER PT J AU Otto, MW Hinton, DE AF Otto, Michael W. Hinton, Devon E. TI Modifying exposure-based CBT for Cambodian refugees with posttraumatic stress disorder SO COGNITIVE AND BEHAVIORAL PRACTICE LA English DT Article ID SOUTHEAST-ASIAN REFUGEES; GENERALIZED ANXIETY DISORDER; COGNITIVE-BEHAVIOR THERAPY; PANIC-DISORDER; CONCENTRATION-CAMPS; RAPE VICTIMS; TRAUMA; DEPRESSION; HEALTH; COMBINATION AB Cambodian refugees represent it severely traumatized population living in the United States. In this paper, we describe the modification of a cognitive-behavior therapy Program to facilitate delivery of an exposure-based treatment for Posttraumatic stress disorder while addressing some of the challenges brought by differences in language and culture between providers and Patients. Our treatment modocations include the use of metaphors and culturally relevant examples to aid the communication of core concepts by interpreters, an emphasis on teaching the "process" of exposure therapy rather than relying on specific exposure practice in the group setting, a focus on interoceptive exposure to allow more effective group practice and to address culturally specific symptom interpretations, attention to the way in which treatment procedures interacted with culturally specific beliefs, and efforts to integrate treatment services within the community. Although data are limited, results to date suggest that this modified treatment was acceptable, to patients and offered benefits on the order of large effect sizes. C1 Boston Univ, Ctr Anxiety & Related Disorders, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Otto, MW (reprint author), Boston Univ, Ctr Anxiety & Related Disorders, 648 Beacon St,Floor 6, Boston, MA 02215 USA. EM MWOTTO@BU.EDU FU NIMH NIH HHS [K23 MH066253, K23 MH066253-05, R01 MH094312] NR 42 TC 18 Z9 18 U1 2 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1077-7229 J9 COGN BEHAV PRACT JI Cogn. Behav. Pract. PD NOV PY 2006 VL 13 IS 4 BP 261 EP 270 DI 10.1016/j.cbpra.2006.04.007 PG 10 WC Psychology, Clinical SC Psychology GA 174HY UT WOS:000246934200004 PM 20072706 ER PT J AU Hinton, DE Safren, SA Pollack, MH Tran, M AF Hinton, Devon E. Safren, Steven A. Pollack, Mark H. Tran, Minh TI Cognitive-behavior therapy for Vietnamese refugees with PTSD and comorbid panic attacks SO COGNITIVE AND BEHAVIORAL PRACTICE LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; GENERALIZED ANXIETY DISORDER; TREATMENT-RESISTANT PTSD; CAMBODIAN REFUGEES; CATASTROPHIC COGNITIONS; APPLIED RELAXATION; CHEST-PAIN; PREVALENCE; TORTURE; PSYCHOPATHOLOGY AB For Vietnamese refugees, we describe (a) how headache- and orthostasis-focused panic attacks are generated, (b) a culturally sensitive treatment for PTSD with comorbid headache- and orthostasis-focused panic attacks, and (c) the outcome of a treatment series. In a mulople-baseline, across-subjects design (N=3), all patients demonstrated livatment-related improvement of headache- and orthostasis-associated panic attacks, and in the repeated-measures, within-subjects design, all patients greatly improved across treatment on measures of psychopathology. One treatment case is presented. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Arbour Conseling Serv, Lowell, MA USA. RP Hinton, DE (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 15 Parkman St,WACC 12, Boston, MA 02114 USA. EM devon_hinton@hms.harvard.edu NR 66 TC 9 Z9 9 U1 3 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1077-7229 J9 COGN BEHAV PRACT JI Cogn. Behav. Pract. PD NOV PY 2006 VL 13 IS 4 BP 271 EP 281 DI 10.1016/j.cbpra.2006.04.008 PG 11 WC Psychology, Clinical SC Psychology GA 174HY UT WOS:000246934200005 ER PT J AU Schulz, PM Huber, LC Resick, PA AF Schulz, Priscilla M. Huber, L. Christian Resick, Patricia A. TI Practical adaptations of cognitive processing therapy with Bosnian refugees: Implications for adapting practice to a multicultural clientele SO COGNITIVE AND BEHAVIORAL PRACTICE LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; FORMER YUGOSLAVIA; MENTAL-HEALTH; VIETNAMESE REFUGEES; PANIC DISORDER; SYMPTOMS; PTSD; TRAUMA; PREVALENCE; SURVIVORS AB Recent findings suggest that established psychological treatments for PTSD are effective for diverse populations, including war refugees who have experienced multiple and severe losses, deprivations, hardships, and atrocities. Treating non-English-speaking traumatized refugees requires the clinician to overcome linguistic and various cultural dissimilarities with clients that complicate effective engagement. Examples of clinical adaptations for Bosnian clients are presented along with a discussion of the client's and therapist's relationship to the larger service delivery system. C1 Univ Missouri, Ctr Trauma Recovery, St Louis, MO 63121 USA. VA Boston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. Boston Univ, Boston, MA 02215 USA. RP Schulz, PM (reprint author), Univ Missouri, Ctr Trauma Recovery, 1 Univ Blvd, St Louis, MO 63121 USA. EM wtr@stlouis.missouri.org NR 68 TC 9 Z9 9 U1 3 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1077-7229 J9 COGN BEHAV PRACT JI Cogn. Behav. Pract. PD NOV PY 2006 VL 13 IS 4 BP 310 EP 321 DI 10.1016/j.cbpra.2006.04.019 PG 12 WC Psychology, Clinical SC Psychology GA 174HY UT WOS:000246934200009 ER PT J AU Schulz, PM Resick, PA Huber, LC Griffin, MG AF Schulz, Priscilla M. Resick, Patricia A. Huber, L. Christian Griffin, Michael G. TI The effectiveness of cognitive processing therapy for PTSD with refugees in a community setting SO COGNITIVE AND BEHAVIORAL PRACTICE LA English DT Article ID POSTTRAUMATIC-STRESS-DISORDER; CAMBODIAN REFUGEES; EXPOSURE THERAPY; BEHAVIOR THERAPY; BOSNIAN REFUGEES; PSYCHOTHERAPY; SYMPTOMS; INTERPRETERS; TRIALS; WELL AB Opinions vary on the generalizability of empirically supported treatments to diverse populations in naturalistic settings and on the relative merits of delivering treatments through interpreters. The authors present statistical analyses of outcome data from a community mental health program that served foreign-born refugees resettled in the U.S. The program used a manualized, empirically supported treatment, Cognitive Processing Therapy, to address symptoms of PTSD in this population. Participants received psychological treatment in native languages either with a therapist who spoke their language or with a therapist who used an interpreter Results demonstrated that treatment of PTSD was highly effective whether delivered directly or through an interpreter. C1 VA Poston Healthcare Syst, Natl Ctr PTSD, Boston, MA USA. Boston Univ, Boston, MA 02215 USA. Univ Missouri, St Louis, MO 63121 USA. RP Resick, PA (reprint author), Boston VAHC, Natl Ctr PTSD, 116B3,150 S Huntington Ave, Boston, MA 02130 USA. EM Patricia.Resick@va.gov NR 62 TC 44 Z9 46 U1 3 U2 20 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1077-7229 J9 COGN BEHAV PRACT JI Cogn. Behav. Pract. PD NOV PY 2006 VL 13 IS 4 BP 322 EP 331 DI 10.1016/j.cbpra.2006.04.011 PG 10 WC Psychology, Clinical SC Psychology GA 174HY UT WOS:000246934200010 ER PT J AU Kline, JA Hernandez-Nino, J Rose, GA Norton, HJ Camargo, CA AF Kline, Jeffrey A. Hernandez-Nino, Jackeline Rose, Geoffrey A. Norton, H. James Camargo, Carlos A., Jr. TI Surrogate markers for adverse outcomes in normotensive patients with pulmonary embolism SO CRITICAL CARE MEDICINE LA English DT Article DE prognosis; fibrinolysis; troponin; thromboembolism; brain natriuretic peptide; electrocardiography; D-dimer; echocardiography ID RIGHT-VENTRICULAR DYSFUNCTION; BRAIN NATRIURETIC PEPTIDE; CARDIAC TROPONIN-I; DEEP-VEIN THROMBOSIS; 6-MINUTE WALK TEST; THROMBOLYTIC THERAPY; PROGNOSTIC VALUE; ECHOCARDIOGRAPHY DOPPLER; THROMBOEMBOLIC DISEASE; MULTICENTER REGISTRY AB Background. Although echocardiography has proven utility in risk stratifying normotensive patients with pulmonary embolism, echocardiography is not always available. Objective. Test if a novel panel consisting of pulse oximetry, 12-lead electrocardiography, and serum troponin T would have prognostic equivalence to echocardiography and to examine the prognostic performance of age, previous cardiopulmonary disease, D-dimer, brain natriuretic peptide, and percentage of pulmonary vascular occlusion on chest computed tomography. Design. Prospective cohort study. Patients and Setting: Normotensive (systolic blood pressure of >100 mm Hg) emergency department and hospital inpatients with diagnosed pulmonary embolism who underwent cardiologist-interpreted echocardiography and other measurements within 15 hrs of anticoagulation. Measurements and Main Results. End points were in-hospital circulatory shock or intubation, or death, recurrent pulmonary embolism, or severe cardiopulmonary disability (defined as echocardiographic evidence of severe right ventricular dysfunction with New York Heart Association class III dyspnea or 6-min walk test of <330 m) at 6-month follow-up. The two-one-sided test tested the hypothesis of equivalence with one-tailed alpha = 0.05 and Delta = 5%. Of 200 patients enrolled, data were complete for 181 (88%); 51 of 181 patients (28%) had an adverse outcome, including in-hospital complication (n = 18), death (n = 11), recurrent pulmonary embolism (n = 2), or cardiopulmonary disability (n=20). Right ventricular dysfunction on initial echocardiogram was 61% sensitive (95% confidence interval, 46-74%) and 57% specific (48-66%). The panel was 71% sensitive (56-83%) and 62% specific (53-71%). The two-one-sided procedure demonstrated superiority of the panel to echocardiography for both sensitivity and noninferiority for specificity. No other biomarker demonstrated equivalence, noninferiority, or superiority for sensitivity and specificity. Conclusion: Normotensive patients with pulmonary embolism have a high rate of severe adverse outcomes during 6-month follow-up. A panel of three widely available tests can be used to risk stratify patients with pulmonary embolism when formal echocardiography is not available. C1 Carolinas Med Ctr, Dept Emergency Med, Charlotte, NC 28203 USA. Carolinas Med Ctr, Dept Cardiol, Charlotte, NC 28203 USA. Carolinas Med Ctr, Dept Biostat, Charlotte, NC 28203 USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Kline, JA (reprint author), Carolinas Med Ctr, Dept Emergency Med, Charlotte, NC 28203 USA. FU NHLBI NIH HHS [R01 HL074384] NR 55 TC 54 Z9 55 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD NOV PY 2006 VL 34 IS 11 BP 2773 EP 2780 DI 10.1097/01.CCM.0000241154.55444.63 PG 8 WC Critical Care Medicine SC General & Internal Medicine GA 100AQ UT WOS:000241639900009 PM 16943732 ER PT J AU Billings, JA Keeley, A Bauman, J Cist, A Coakley, E Dahlin, C Montgomery, P Thompson, T Wise, M AF Billings, J. Andrew Keeley, Adele Bauman, Joel Cist, Alex Coakley, Edward Dahlin, Connie Montgomery, Paul Thompson, Taylor Wise, Marilyn CA Massachusetts Gen Hosp Palliative TI Merging cultures: Palliative care specialists in the medical intensive care unit SO CRITICAL CARE MEDICINE LA English DT Article; Proceedings Paper CT Annual Conference of the Society-of-Critical-Care-Medicine CY FEB 17-18, 2006 CL Miami, FL SP Soc Crit Care Med DE intensive care unit; palliative care; end of life AB We summarize the key interventions and general findings from a 3-yr project titled, "Merging Palliative and Critical Care Cultures in the Medical Intensive Care Unit." This multifaceted demonstration project was designed so palliative care and intensive care clinicians would share their expertise and develop projects that promote end-of-life care in a medical intensive care unit (ICU) setting. A variety of interventions are described, including collaborating with ICU leaders, training nurses as "palliative care champions," opening visiting hours, educating house officers and other staff about relevant palliative practices, establishing the presence of a palliative care specialist during work rounds, teaching about and promoting family meetings, introducing a "Get to Know Me" poster, staff support efforts, and modeling of interdisciplinary teamwork. Additional problems were noted but not well addressed, particularly routine communication with families and continuity of care for complex patients leaving the ICU. C1 Massachusetts Gen Hosp, Palliat Care Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Ctr Palliat Care, Boston, MA 02115 USA. Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Patient Care Serv, Boston, MA 02114 USA. RP Billings, JA (reprint author), Massachusetts Gen Hosp, Palliat Care Serv, Boston, MA 02114 USA. NR 0 TC 26 Z9 26 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD NOV PY 2006 VL 34 IS 11 SU S BP S388 EP S393 DI 10.1097/01.CCM.0000237346.11218.42 PG 6 WC Critical Care Medicine SC General & Internal Medicine GA 101JP UT WOS:000241737400015 PM 17057603 ER PT J AU Mularski, RA Curtis, JR Billings, JA Burt, R Byock, I Fuhrman, C Mosenthal, AC Medina, J Ray, DE Rubenfeld, GD Schneiderman, LJ Treece, PD Truog, RD Levy, MM AF Mularski, Richard A. Curtis, J. Randall Billings, J. Andrew Burt, Robert Byock, Ira Fuhrman, Cathy Mosenthal, Anne C. Medina, Justine Ray, Daniel E. Rubenfeld, Gordon D. Schneiderman, Lawrence J. Treece, Patsy D. Truog, Robert D. Levy, Mitchell M. TI Proposed quality measures for palliative care in the critically ill: A consensus from the Robert wood Johnson Foundation Critical Care Workgroup SO CRITICAL CARE MEDICINE LA English DT Review DE quality of health care; quality indicators; end-of-life care; measures; intensive care; critical care; dying; outcome and process assessment; end-of-life care; terminal care ID OF-LIFE CARE; INTENSIVE-CARE; STANDARDIZED PATIENTS; HOSPITALIZED-PATIENTS; FAMILY-MEMBERS; UNITED-STATES; HEALTH-CARE; END; COMMUNICATION; INDICATORS AB For critically ill patients and their loved ones, high-quality health care includes the provision of excellent palliative care. To achieve this goal, the healthcare system needs to identify, measure, and report specific targets for quality palliative care for critically ill or injured patients. Our objective was to use a consensus process to develop a preliminary set of quality measures to assess palliative care in the critically ill. We built on earlier and ongoing efforts of the Robert Wood Johnson Foundation Critical Care End-of-Life Peer Workgroup to propose specific measures of the structure and process of palliative care. We used an informal iterative consensus process to identify and refine a set of candidate quality measures. These candidate measures were developed by reviewing previous literature reviews, supplementing the evidence base with recently published systematic reviews and consensus statements, identifying existing indicators and measures, and adapting indicators from related fields for our objective. Among our primary sources, we identified existing measures from the Voluntary Hospital Association's Transformation of the ICU program and a government-sponsored systematic review performed by RAND Health to identify palliative care quality measures for cancer care. Our consensus group proposes 18 quality measures to assess the quality of palliative care for the critically ill and injured. A total of 14 of the proposed measures assess processes of care at the patient level, and four measures explore structural aspects of critical care delivery. Future research is needed to assess the relationship of these measures to desired health outcomes. Subsequent measure sets should also attempt to include outcome measures, such as patient or surrogate satisfaction, as the field develops the means to rigorously measure such outcomes. The proposed measures are intended to stimulate further discussion, testing, and refinement for quality of care measurement and enhancement. C1 Kaiser Permanente NW, Ctr Hlth Res, Portland, OR 97232 USA. Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97201 USA. Univ Washington, Harborview Med Ctr, Div Pulm & Crit Care Med, Dept Med,Sch Med, Seattle, WA 98195 USA. Massachusetts Gen Hosp, Palliat Care Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Ctr Palliat Care, Boston, MA USA. Yale Univ, Sch Law, New Haven, CT 06520 USA. Dartmouth Hitchcock Med Ctr, Palliat Care Program, Lebanon, NH 03766 USA. Dartmouth Med Sch, Dept Anesthesiol, Lebanon, NH USA. Dartmouth Med Sch, Dept Community & Family Med, Lebanon, NH USA. Lehigh Valley Hosp, Med Crit Care Program, Dept Med, Allentown, PA USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Div Trauma & Crit Care, Dept Surg, Newark, NJ 07103 USA. Amer Assoc Crit Care Nurses, Profess Practice & Programs, Allentown, PA USA. Lehigh Valley Hosp, Dept Med, Allentown, PA USA. Pulm Assoc, Allentown, PA USA. Univ Calif San Diego, Dept Family & Prevent Med, San Diego, CA 92103 USA. Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA. Childrens Hosp Boston, Div Crit Care Med, Dept Anesthesia, Boston, MA USA. Harvard Univ, Sch Med, Div Med Eth, Dept Social Med, Boston, MA USA. Brown Univ, Sch Med, Rhode Isl Hosp, Dept Med, Providence, RI 02912 USA. RP Byock, I (reprint author), Kaiser Permanente NW, Ctr Hlth Res, Portland, OR 97232 USA. NR 64 TC 77 Z9 77 U1 3 U2 16 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD NOV PY 2006 VL 34 IS 11 SU S BP S404 EP S411 DI 10.1097/01.CCM.0000242910.00801.53 PG 8 WC Critical Care Medicine SC General & Internal Medicine GA 101JP UT WOS:000241737400018 PM 17057606 ER PT J AU Siker, ML Chakravarti, A Mehta, MP AF Siker, Malika L. Chakravarti, Arnab Mehta, Minesh P. TI Should concomitant and adjuvant treatment with temozolomide be used as standard therapy in patients with anaplastic glioma? SO CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY LA English DT Review DE anaplastic glioma; astrocytoma; oligodendroglioma; oligoastrocytoma; temozolomide; radiotherapy; chemotherapy; chemoradiotherapy ID GROWTH-FACTOR RECEPTOR; DIAGNOSED GLIOBLASTOMA-MULTIFORME; PHASE-II TRIAL; O-6-ALKYLGUANINE-DNA ALKYLTRANSFERASE ACTIVITY; O-6-METHYLGUANINE-DNA METHYLTRANSFERASE GENE; POLY(ADP-RIBOSE) POLYMERASE-1 INHIBITOR; CARMUSTINE PLUS O-6-BENZYLGUANINE; PROGRESSIVE MALIGNANT GLIOMA; VINCRISTINE PCV CHEMOTHERAPY; MISMATCH REPAIR-DEFICIENT AB Malignant gliomas are devastating tumors associated with poor prognosis. Standard treatment has been surgery followed by radiotherapy while the role of chemotherapy has remained controversial. Concomitant and adjuvant treatment with temozolomide has recently been shown to improve survival in patients with glioblastoma. While it seems intuitive to apply this regimen to patients with anaplastic gliomas which have traditionally been considered more chemosensitive, chemotherapy has not been shown to prolong life in patients with anaplastic gliomas. Despite promising preclinical and early clinical results, there is currently not enough level I evidence to justify concomitant and adjuvant temozolomide as standard therapy for patients with newly diagnosed anaplastic gliomas. Further investigation is needed to better define the role of chemotherapy in patients with anaplastic gliomas. Trials evaluating chemoradiotherapy as well as targeted therapeutic agents are the subject of further research. (c) 2006 Elsevier Ireland Ltd. All rights reserved. C1 Univ Wisconsin, Sch Med & Publ Hlth, Dept Human Oncol, Madison, WI 53792 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02115 USA. RP Mehta, MP (reprint author), Univ Wisconsin, Sch Med & Publ Hlth, Dept Human Oncol, 600 Highland Ave,K4-3, Madison, WI 53792 USA. EM mehta@humonc.wisc.edu OI mehta, minesh/0000-0002-4812-5713 NR 93 TC 24 Z9 24 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1040-8428 J9 CRIT REV ONCOL HEMAT JI Crit. Rev. Oncol./Hematol. PD NOV PY 2006 VL 60 IS 2 BP 99 EP 111 DI 10.1016/j.critrevonc.2006.04.005 PG 13 WC Oncology; Hematology SC Oncology; Hematology GA 108MJ UT WOS:000242243600002 PM 17027279 ER PT J AU Crivera, C Suh, DC Huang, ES Cagliero, E Grant, RW Vo, L Shin, HC Meigs, JB AF Crivera, C. Suh, D. C. Huang, E. S. Cagliero, E. Grant, R. W. Vo, L. Shin, H. C. Meigs, J. B. TI The incremental costs of recommended therapy versus real world therapy in type 2 diabetes patients SO CURRENT MEDICAL RESEARCH AND OPINION LA English DT Article DE cardiovascular disease; cost studies; disease management; health services research; pharmacoepidemiology; type 2 diabetes ID CARDIOVASCULAR-DISEASE; GLYCEMIC CONTROL; COMPLICATIONS; MANAGEMENT; MELLITUS; US; HYPERTENSION; ADULTS; RISK AB Background: The goals of diabetes management have evolved over the past decade to become the attainment of near-normal glucose and cardiovascular risk factor levels. Improved metabolic control is achieved through optimized medication regimens, but costs specifically associated with such optimization have not been examined. Objective: To estimate the incremental medication cost of providing optimal therapy to reach recommended goals versus actual therapy in patients with type 2 diabetes. Methods: We randomly selected the charts of 601 type 2 diabetes patients receiving care from the outpatient clinics of Massachusetts General Hospital March 1, 1996-August 31, 1997 and abstracted clinical and medication data. We applied treatment algorithms based on 2004 clinical practice guidelines for hyperglycemia, hyperlipidemia, and hypertension to patients' current medication therapy to determine how current medication regimens could be improved to attain recommended treatment goals. Four clinicians and three pharmacists independently applied the algorithms and reached consensus on recommended therapies. Mean incremental medication costs, the cost differences between current and recommended therapies, per patient (expressed in 2004 dollars) were calculated with 95% bootstrap confidence intervals (CIs). Results: Mean patient age was 65 years old, mean duration of diabetes was 7.7 years, 32% had ideal glucose control, 25% had ideal systolic blood pressure, and 24% had ideal low-density lipoprotein cholesterol. Care for these density diabetes patients was similar to that observed in recent national studies. If treatment algorithm recommendations were applied, the average annual medication cost/ patient would increase from $1525 to $2164. Annual incremental costs/ patient increased by $168 (95% CI $133 $206) for antihyperglycemic medications, $75 ($57-$93) for antihypertensive medications, $392 ($354-$434) for antihyperlipidemic medications, and $3 ($3-$4) for aspirin prophylaxis. Yearly incremental cost of recommended laboratory testing ranged from $77-$189/ patient. Limitations: Although baseline data come from the clinics of a single academic institution, collected in 1997, the care of these diabetes patients was remarkably similar to care recently observed nationally. In addition, the data are dependent on the medical record and may not accurately reflect patients' actual experiences. Conclusion: Average yearly incremental cost of optimizing drug regimens to achieve recommended treatment goals for type 2 diabetes was approximately $600/ patient. These results provide valuable input for assessing the cost-effectiveness of improving comprehensive diabetes care. C1 Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Rutgers State Univ, Ernest Mario Sch Pharm, Piscataway, NJ USA. Univ Chicago, Chicago, IL 60637 USA. Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Clin Res Program, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Meigs, JB (reprint author), Massachusetts Gen Hosp, Div Gen Med, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM jmeigs@partners.org OI Grant, Richard/0000-0002-6164-8025 FU NIA NIH HHS [K23 AG021963-01A1, K23 AG021963]; NIDDK NIH HHS [K23 DK067452-01A1, K23 DK067452] NR 30 TC 3 Z9 3 U1 0 U2 2 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 NOV PY 2006 VL 22 IS 11 BP 2301 EP 2311 DI 10.1185/030079906X132523 PG 11 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA 103NS UT WOS:000241894300024 PM 17076990 ER PT J AU Johnson, KA AF Johnson, Keith A. TI Amyloid imaging of Alzheimer's disease using Pittsburgh Compound B SO CURRENT NEUROLOGY AND NEUROSCIENCE REPORTS LA English DT Review AB The advent of human amyloid imaging represents a research breakthrough in Alzheimer's disease (AD). It is now possible to detect the early stages of cerebral amyloidosis, a major pathologic component of AD, in living humans using positron emission tomography (PET). This technology will likely enable earlier AD diagnosis, but further research is required to determine whether a positive amyloid PET scan predicts imminent decline in questionably or mildly impaired individuals, and whether amyloid PET can be used to track the efficacy of emerging antiamyloid therapeutic agents. Initial human data are encouraging but suggest that individual amyloid PET findings should be interpreted cautiously, because cerebral amyloidosis precedes and does not equate with either clinical AD or pathologic criteria that define AD. C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Johnson, KA (reprint author), Massachusetts Gen Hosp, Dept Radiol, Tilton 201, Boston, MA 02114 USA. EM kajohnson@partners.org NR 54 TC 15 Z9 15 U1 0 U2 0 PU CURRENT SCIENCE INC PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1528-4042 J9 CURR NEUROL NEUROSCI JI Curr. Neurol. Neurosci. Rep. PD NOV PY 2006 VL 6 IS 6 BP 496 EP 503 DI 10.1007/s11910-006-0052-5 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA V54FO UT WOS:000203664800007 PM 17074285 ER PT J AU Greer, DM AF Greer, David M. TI Hypothermia for cardiac arrest SO CURRENT NEUROLOGY AND NEUROSCIENCE REPORTS LA English DT Review AB Therapeutic hypothermia for cardiac arrest survivors has emerged as a highly effective means of improving neurologic outcome. There are a number of purported mechanisms by which it is felt to be effective, but the exact mechanism is unknown. This article reviews the biochemical mechanisms of injury occurring in cardiac arrest, as well as the avenues that hypothermia takes to combat this injury. It also reviews the animal model data in support of this, as well as the newer animal studies that may help to improve the field. Several human studies of hypothermia in cardiac arrest have been performed, and this article reviews these for their methods and shortcomings. Our currently recommended guidelines for performing therapeutic hypothermia are presented. With therapeutic hypothermia comes potential risks to the patient, primarily affecting cardiac, metabolic, and hematologic systems, and these risks and their management are discussed. Multiple methods of cooling exist, including selective cranial as well as systemic cooling by internal or external approaches. Finally, the article discusses the current research in the field of hypothermia for cardiac arrest and implications for future practice. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Greer, DM (reprint author), Massachusetts Gen Hosp, ACC 835,55 Fruit St, Boston, MA 02114 USA. EM dgreer@partners.org NR 43 TC 4 Z9 4 U1 0 U2 0 PU CURRENT SCIENCE INC PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1528-4042 J9 CURR NEUROL NEUROSCI JI Curr. Neurol. Neurosci. Rep. PD NOV PY 2006 VL 6 IS 6 BP 518 EP 524 DI 10.1007/s11910-006-0055-2 PG 7 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA V54FO UT WOS:000203664800009 PM 17074288 ER PT J AU Dong, MH Kaunitz, JD AF Dong, Mamie H. Kaunitz, Jonathan D. TI Gastroduodenal mucosal defense SO CURRENT OPINION IN GASTROENTEROLOGY LA English DT Article DE annexin-1; antioxidants; esophagus; ghrelin; Helicobacter pylori; reactive oxygen species ID HELICOBACTER-PYLORI INFECTION; REACTIVE OXYGEN METABOLITES; GASTRIC EPITHELIAL-CELLS; RAT DUODENAL MUCOSA; ACID-INDUCED INJURY; FUNCTIONAL DYSPEPSIA; CARBONIC-ANHYDRASES; GHRELIN LEVELS; BLOOD-FLOW; IN-VIVO AB Purpose of review The duodenum absorbs nearly all secreted gastric acid. Carbonic anhydrases facilitate transmucosal acid movement. The upper gastrointestinal tract must resist a variety of injuries, including those caused by ingested noxious substances, acid, ischemia/reperfusion, and infections such as Helicobacter pylori. The results are similar, however, regardless of insult: inflammation, ulceration, or metaplasia/dysplasia. In the past year, there have been prominent findings suggesting that oxidative stress and the formation of reactive oxygen species may play a pivotal role in all forms of injury, and that antioxidants may be the key to injury prevention and healing. Recent findings Oxidative injury may be a common mechanism by which the upper gastrointestinal mucosa responds to noxious insults. Endogenous antioxidants, such as ghrelin, L-carnitine, and annexin-1 attenuate the oxidative-stress response. Similarly, exogenous antioxidants have also been shown to decrease inflammation, upregulate free radical scavengers, and prevent the formation of reactive oxygen species. Summary Many studies published in the past year have linked oxidative stress to a variety of upper gastrointestinal insults. Exogenous and endogenous antioxidant compounds prevent the oxidative stress response. The future holds great promise for the development of pharmaceuticals with antioxidant properties that are safe, efficacious, and inexpensive. C1 W Los Angeles Vet Affairs Med Ctr, Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Med Ctr, Dept Internal Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Med, Dept Med, CURE Digest Dis Res Ctr, Los Angeles, CA 90024 USA. Brentwood Biomed Res Inst, Los Angeles, CA USA. RP Kaunitz, JD (reprint author), W Los Angeles Vet Affairs Med Ctr, Greater Los Angeles Vet Affairs Healthcare Syst, Bldg 114,Suite 217, Los Angeles, CA 90073 USA. EM jake@ucla.edu FU NIDDK NIH HHS [P30 DK0413, R01 DK54221] NR 66 TC 18 Z9 21 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0267-1379 J9 CURR OPIN GASTROEN JI Curr. Opin. Gastroenterol. PD NOV PY 2006 VL 22 IS 6 BP 599 EP 606 DI 10.1097/01.mog.0000245540.87784.75 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 106WI UT WOS:000242132300003 PM 17053436 ER PT J AU Richardson, PG Mitsiades, C Ghobrial, I Anderson, K AF Richardson, Paul G. Mitsiades, Constantine Ghobrial, Irene Anderson, Kenneth TI Beyond single-agent bortezomib: combination regimens in relapsed multiple myeloma SO CURRENT OPINION IN ONCOLOGY LA English DT Review DE bortezomib; combination regimens; multiple myeloma; refractory; relapsed AB Purpose of review Bortezomib-based combinations are being investigated in relapsed or refractory multiple myeloma with the aim of improving outcomes. This review presents recent data from clinical trials of these combinations and discusses their implications. Recent findings Preclinical findings indicating additive or synergistic activity of bortezomib plus conventional and novel agents for multiple myeloma appear to be supported by clinical studies of bortezomib-based combinations. Bortezomib combined with a broad set of active agents results in enhanced response rates, including high complete response rates. Encouraging responses to bortezomib and its combinations are also seen in elderly patients, patients with adverse prognostic factors such as refractory disease and increased beta(2)-microglobulin, patients with cytogenetic abnormalities such as chromosome 13 deletion, advanced bone disease, extramedullary involvement, and patients with renal impairment, including patients with renal failure requiring dialysis. Toxicities are predictable and manageable and comparable to those seen with bortezomib monotherapy. Summary Bortezomib-based combinations show promising activity in relapsed or refractory multiple myeloma, including reversal of chemoresistance to previously used agents. As high complete and overall response rates translate into longer survival, bortezomib-based combinations appear likely to have a significant impact on the multiple myeloma treatment algorithm and on the course of the disease itself. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Richardson, PG (reprint author), Dana Farber Canc Inst, 44 Binney St,Dana 1B02, Boston, MA 02115 USA. EM Paul_Richardson@dfci.harvard.edu NR 75 TC 26 Z9 27 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8746 J9 CURR OPIN ONCOL JI Curr. Opin. Oncol. PD NOV PY 2006 VL 18 IS 6 BP 598 EP 608 DI 10.1097/01.cco.0000245320.34658.bd PG 11 WC Oncology SC Oncology GA V44CV UT WOS:000202981700008 PM 16988581 ER PT J AU Dinh, TL Veves, A AF Dinh, Thanh L. Veves, Aristidis TI Treatment of diabetic ulcers SO DERMATOLOGIC THERAPY LA English DT Article DE diabetic foot ulceration; impaired wound healing; pathogenesis; management ID FOOT ULCERS; TRIAL AB Diabetic ulcers are chronic wounds that are the result of repetitive trauma in the insensate foot. The presence of infection and peripheral vascular disease makes the treatment of these wounds demanding and requires a multidisciplinary approach. The main principles of the management include adherence to the principles of good wound care, such as aggressive debridement of all non-viable tissue, adequate off-loading of pressure, prompt treatment of infection and moist wound dressings. Over the last decade, new therapeutic modalities, including growth factors and living skin equivalents, have been available to the practicing physicians. Judicious use of advanced wound care products may provide the best means of treating these challenging wounds in an efficient and cost-effective way. C1 Joslin Beth Israel Deaconess Foot Ctr, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Div Podiatry, Boston, MA 02215 USA. Harvard Univ, Sch Med, Microcirculat Lab, Boston, MA USA. RP Veves, A (reprint author), Joslin Beth Israel Deaconess Foot Ctr, 1 Deaconess Rd, Boston, MA 02215 USA. EM aveves@bidmc.harvard.edu NR 15 TC 15 Z9 18 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1396-0296 J9 DERMATOL THER JI Dermatol. Ther. PD NOV-DEC PY 2006 VL 19 IS 6 BP 348 EP 355 DI 10.1111/j.1529-8019.2006.00093.x PG 8 WC Dermatology SC Dermatology GA 116DF UT WOS:000242782000005 PM 17199677 ER PT J AU Lewis, A Green, K Dawson, C Redrup, L Huynh, KD Lee, JT Hemberger, M Reik, W AF Lewis, Annabelle Green, Kelly Dawson, Claire Redrup, Lisa Huynh, Khanh D. Lee, Jeannie T. Hemberger, Myriam Reik, Wolf TI Epigenetic dynamics of the Kcnq1 imprinted domain in the early embryo SO DEVELOPMENT LA English DT Article DE epigenetics; imprinting; ES and TS cells; Kcnq1 domain; mouse ID X-CHROMOSOME INACTIVATION; REPRESSIVE HISTONE METHYLATION; EARLY MOUSE DEVELOPMENT; DNA METHYLATION; STEM-CELLS; EXPRESSION; GENES; IMPLANTATION; GENOME; LOCUS AB The mouse Kcnq1 imprinted domain is located on distal chromosome 7 and contains several imprinted genes that are paternally repressed. Repression of these genes is regulated by a non-coding antisense transcript, Kcnq1ot1, which is paternally expressed. Maternal repression of Kcnq1ot1 is controlled by DNA methylation originating in the oocyte. Some genes in the region are imprinted only in the placenta, whereas others are imprinted in both extra-embryonic and embryonic lineages. Here, we show that Kcnq1ot1 is paternally expressed in preimplantation embryos from the two-cell stage, and that ubiquitously imprinted genes proximal to Kcnq1ot1 are already repressed in blastocysts, ES cells and TS cells. Repressive histone marks such as H3K27me3 are present on the paternal allele of these genes in both ES and TS cells. Placentally imprinted genes that are distal to Kcnq1ot1, by contrast, are not imprinted in blastocysts, ES or TS cells. In these genes, paternal silencing and differential histone marks arise during differentiation of the trophoblast lineage between E4.5 and E7.5. Our findings show that the dynamics during preimplantation development of gene inactivation and acquisition of repressive histone marks in ubiquitously imprinted genes of the Kcnq1 domain are very similar to those of imprinted X inactivation. By contrast, genes that are only imprinted in the placenta, while regulated by the same non-coding RNA transcript Kcnq1ot1, undergo epigenetic inactivation during differentiation of the trophoblast lineage. Our findings establish a model for how epigenetic gene silencing by non-coding RNA may depend on distance from the non-coding RNA and on lineage and differentiation specific factors. C1 Babraham Inst, Lab Dev Genet & Imprinting, Cambridge CB2 4AT, England. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Howard Hughes Med Inst,Dept Mol Biol,Dept Genet, Boston, MA 02114 USA. RP Reik, W (reprint author), Babraham Inst, Lab Dev Genet & Imprinting, Cambridge CB2 4AT, England. EM wolf.reik@bbsrc.ac.uk RI Reik, Wolf/I-6794-2012; OI Reik, Wolf/0000-0003-0216-9881 FU Biotechnology and Biological Sciences Research Council [BBS/E/B/0000M100]; Medical Research Council [G0400154, G120/824] NR 40 TC 59 Z9 61 U1 1 U2 4 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD NOV 1 PY 2006 VL 133 IS 21 BP 4203 EP 4210 DI 10.1242/dev.02612 PG 8 WC Developmental Biology SC Developmental Biology GA 094CR UT WOS:000241217400008 PM 17021040 ER PT J AU Ohshiro, Y Ma, RC Yasuda, Y Hiraoka-Yamamoto, J Clermont, AC Isshiki, K Yagi, K Arikawa, E Kern, TS King, GL AF Ohshiro, Yuzuru Ma, Ronald C. Yasuda, Yutaka Hiraoka-Yamamoto, Junko Clermont, Allen C. Isshiki, Keiji Yagi, Kunimasa Arikawa, Emi Kern, Timothy S. King, George L. TI Reduction of diabetes-induced oxidative stress, fibrotic cytokine expression, and renal dysfunction in protein kinase C beta - Null mice SO DIABETES LA English DT Article ID GROWTH-FACTOR-BETA; NAD(P)H OXIDASE; SUPEROXIDE PRODUCTION; INSULIN-RESISTANCE; ENDOTHELIAL-CELL; GENE-EXPRESSION; NADPH OXIDASE; NEPHROPATHY; ACTIVATION; RATS AB Diabetes induces the activation of several protein kinase C (PKC) isoforms in the renal glomeruli. We used PKC-beta(-/-) mice to examine the action of PKC-beta isoforms in diabetes-induced oxidative stress and renal injury at 8 and 24 weeks of disease. Diabetes increased PKC activity in renal cortex of wild-type mice and was significantly reduced (< 50% of wild-type) in diabetic PKC-beta(-/-) mice. In wild-type mice, diabetes increased the translocation of PKC-alpha and -beta 1 to the membrane, whereas only PKC-a was elevated in PKC-beta(-/-) mice. Increases in urinary isoprostane and 8-hydroxydeoxyguanosine, parameters of oxidative stress, in diabetic PKC-beta(-/-) mice were significantly reduced compared with diabetic wild-type mice. Diabetes increased NADPH oxidase activity and the expressions of p47(phox), Nox2, and Nox4 mRNA levels in the renal cortex and were unchanged in diabetic PKC-beta(-/-) mice. Increased expression of endothelin-1 (ET-1), vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-beta, connective tissue growth factor (CTGF), and collagens IV and VI found in diabetic wild-type mice was attenuated in diabetic PKC-beta(-/-) mice. Diabetic PKC-beta(-/-) mice were protected from renal hypertrophy, glomerular enlargement, and hyperfiltration observed in diabetic wild-type mice and had less proteinuria. Lack of PKC-beta can protect against diabetes-induced renal dysfunction, fibrosis, and increased expressions of Nox2 and -4, ET-1, VEGF, TGF-beta, CTGF, and oxidant production. C1 Harvard Univ, Sch Med, Joslin Diabet Ctr, Boston, MA 02215 USA. Case Western Reserve Univ, Dept Med, Cleveland, OH 44106 USA. RP King, GL (reprint author), Harvard Univ, Sch Med, Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM george.king@joslin.harvard.edu RI Ma, Ronald/C-2788-2009 OI Ma, Ronald/0000-0002-1227-803X FU NIDDK NIH HHS [DK071359] NR 45 TC 96 Z9 107 U1 1 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD NOV PY 2006 VL 55 IS 11 BP 3112 EP 3120 DI 10.2337/db06-0895 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 104OA UT WOS:000241966500023 PM 17065350 ER PT J AU Lyon, HN Florez, JC Bersaglieri, T Saxena, R Winckler, W Almgren, P Lindblad, U Tuomi, T Gaudet, D Zhu, XF Cooper, R Ardlie, KG Daly, MJ Altshuler, D Groop, L Hirschhorn, JN AF Lyon, Helen N. Florez, Jose C. Bersaglieri, Todd Saxena, Richa Winckler, Wendy Almgren, Peter Lindblad, Ulf Tuomi, Tiinamaija Gaudet, Daniel Zhu, Xiaofeng Cooper, Richard Ardlie, Kristin G. Daly, Mark J. Altshuler, David Groop, Leif Hirschhorn, Joel N. TI Common variants in the ENPP1 gene are not reproducibly associated with diabetes or obesity SO DIABETES LA English DT Article ID NONDIABETIC MEXICAN-AMERICANS; K121Q POLYMORPHISM; INSULIN-RESISTANCE; CHILDHOOD OBESITY; RISK; PHENOTYPES; LINKAGE; REGION; SUSCEPTIBILITY; POPULATION AB The common missense single nucleotide polymorphism (SNP) K121Q in the ectoenzyme nucleotide pyrophosphate phosphodiesterase (ENPP1) gene has recently been associated with type 2 diabetes in Italian, U.S., and South-Asian populations. A three-SNP haplotype, including K121Q, has also been associated with obesity and type 2 diabetes in French and Austrian populations. We set out to confirm these findings in several large samples. We genotyped the haplotype K121Q (rs1044498), rs1799774, and rs7754561 in 8,676 individuals of European ancestry with and without type 2 diabetes, in 1,900 obese and 930 lean individuals of European ancestry from the U.S. and Poland, and in 1,101 African-American individuals. Neither the K121Q missense polymorphism nor the putative risk haplotype were significantly associated with type 2 diabetes or BMI. Two SNPs showed suggestive evidence of association in a meta-analysis of our European ancestry samples. These SNPs were rs7754561 with type 2 diabetes 0.85 [95% CI 0.78-0.92], P = 0.00003) and rs1799774 with BMI (homozygotes of the delT-allele, 0.6 [0.42-0.88], P = 0.007). However, these findings are not supported by other studies. We did not observe a reproducible association between these three ENPP1 variants and BMI or type 2 diabetes. C1 Childrens Hosp Boston, Div Genet, Program Genom, Boston, MA 02115 USA. Childrens Hosp Boston, Div Endocrinol, Program Genom, Boston, MA 02115 USA. Broad Inst Harvard, Program Med & Populat Genet, Cambridge, MA USA. MIT, Cambridge, MA USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Lund Univ, Univ Hosp MAS, Dept Endocrinol, Malmo, Sweden. Lund Univ, Univ Hosp MAS, Dept Clin Sci, Malmo, Sweden. Univ Helsinki, Cent Hosp, Dept Med, Helsinki, Finland. Univ Helsinki, Res Program Mol Med, Helsinki, Finland. Folkhalsan Res Ctr, Helsinki, Finland. Univ Montreal, Community Genom Med Ctr, Quebec City, PQ, Canada. Chicoutimi Hosp, Lipid Clin, Quebec City, PQ, Canada. Loyola Univ, Ctr Med, Dept Prevet Med & Epidemiol, Maywood, IL 60153 USA. SeraCare LifeSci, Genom Collaborat Div, Cambridge, MA USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Hirschhorn, JN (reprint author), Childrens Hosp Boston, Div Genet, Program Genom, Enders 561,300 Londwood Ave, Boston, MA 02115 USA. EM joelh@broad.mit.edu RI Altshuler, David/A-4476-2009; OI Altshuler, David/0000-0002-7250-4107; Tuomi, Tiinamaija/0000-0002-8306-6202 FU NHLBI NIH HHS [R01 HL54485, R01 HL074166]; NIDDK NIH HHS [K23 DK65978, K23 DK067288] NR 28 TC 54 Z9 54 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD NOV PY 2006 VL 55 IS 11 BP 3180 EP 3184 DI 10.2337/db06-0407 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 104OA UT WOS:000241966500032 PM 17065359 ER PT J AU Wood, JR Moreland, EC Volkening, LK Svoren, BM Butler, DA Laffel, LMB AF Wood, Jamie R. Moreland, Elaine C. Volkening, Lisa K. Svoren, Britta M. Butler, Deborah A. Laffel, Lori M. B. TI Durability of insulin pump use in pediatric patients with type 1 diabetes SO DIABETES CARE LA English DT Article; Proceedings Paper CT 65th Annual Meeting of the American-Diabetes-Association CY JUN 10-14, 2005 CL San Diego, CA SP Amer Diabet Assoc ID RANDOMIZED CONTROLLED-TRIAL; GLYCEMIC CONTROL; YOUNG-CHILDREN; THERAPY; ADOLESCENTS; INFUSION; INVOLVEMENT; PREDICTORS; MANAGEMENT; COUNTRIES AB OBJECTIVE - To examine longitudinal outcomes, rate of and reasons for discontinuation, and predictors of insulin pump success in a cohort of youth initiating pump therapy. RESEARCH DESIGN AND METHODS - We followed a cohort of youth with type 1 diabetes (n = 161) starting the pump between 1998 and 2001 and recorded natural history of treatment. RESULTS - At pump start, patients (71% female) had a mean age of 14.1 +/- 3.7 years, diabetes duration of 7.1 +/- 4.0 years, daily blood glucose monitoring (BGM) frequency of 4.0 +/- 1.2, a daily insulin dose of 1.0 +/- 0.3 units/kg, and an HbA(1c) (A1C) of 8.4 +/- 1.4%. After 1 year, mean daily BGM frequency was 4.5 +/- 1.7, daily insulin dose was 0.8 +/- 0.2 units/kg, and A1C was 8.1 +/- 1.3% (all baseline versus 1-year data, P < 0.01). As of 2005, 29 patients (18%) had resumed injection therapy at a mean age of 17.0 +/- 2.9 years after,a mean duration of pump use of 2.1 +/- 1.3 years. BGM frequency at baseline and at 1 year was significantly lower in the patients who resumed injection therapy (P < 0.02). In addition, patients who remained on the pump had lower A1C than those who resumed injection therapy at both 1 year (P = 0.04) and at the most recent clinic visit (P = 0.01). CONCLUSIONS - After an average of 3.8 years, > 80% of pediatric patients maintained pump therapy with preservation of baseline A1C. Patients discontinuing the pump were less adherent and did not achieve equivalent glycemic benefit compared with continued users; these patients require ongoing support aimed at improving adherence and outcomes. C1 Joslin Diabet Ctr, Pediat Adolescent & Young Adult Sect, Boston, MA 02215 USA. RP Laffel, LMB (reprint author), Joslin Diabet Ctr, Pediat Adolescent & Young Adult Sect, 1 Joslin Pl, Boston, MA 02215 USA. EM lori.laffel@joslin.harvard.edu FU NIDDK NIH HHS [K12 DK063696-03, R01 DK46887, T32 DK063702-03] NR 20 TC 44 Z9 44 U1 0 U2 0 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD NOV PY 2006 VL 29 IS 11 BP 2355 EP 2360 DI 10.2337/dc06-1141 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 105LA UT WOS:000242030200003 PM 17065667 ER PT J AU Carver, C AF Carver, Catherine TI Insulin treatment and the problem of weight gain in type 2 diabetes SO DIABETES EDUCATOR LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; CARDIOVASCULAR RISK-FACTORS; BLOOD-GLUCOSE CONTROL; BASAL-BOLUS REGIMEN; LOW-CALORIE DIET; BODY-MASS INDEX; GLYCEMIC CONTROL; LIFE-STYLE; NPH INSULIN; OBESE-PATIENTS AB PURPOSE Insulin therapy has been shown to benefit the prognosis in patients with type 2 diabetes, but its initiation and intensification is often delayed through concerns about hypoglycemia and weight gain. In addition, weight gain is linked to the pathophysiology of type 2 diabetes and contributes to the overall risk for adverse cardiovascular outcomes. This article attempts to summarize this issue and examine the options available for weight management. METHODS A broad range of literature has been reviewed to distil important, consistent facts about insulin and weight gain and the options available for limiting the problem. RESULTS Unfortunately, the great benefits of insulin therapy may be potentially undermined by weight gain. Weight gain is physiologically and psychologically undesirable, especially in patients with diabetes who are already overweight. Die fear of weight gain with some medications contributes to psychological insulin resistance, which may discourage patients from commencing or following insulin regimens. However, new diabetes treatments and lifestyle interventions can be used to mitigate these problems. CONCLUSIONS The exact choice of insulin and oral medications and weight loss interventions are important considerations in the overall management of patients with type 2 diabetes. Changes in a patient's lifestyle, such as modifications to diet and implementing an exercise program, are first-line treatments for type 2 diabetes and can also counteract insulin-induced weight gain. C1 Joslin Diabet Ctr, Boston, MA 02215 USA. RP Carver, C (reprint author), Joslin Diabet Ctr, 1 Joslin Pl, Boston, MA 02215 USA. EM cathy.carver@joslin.harvard.edu NR 84 TC 48 Z9 52 U1 0 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0145-7217 EI 1554-6063 J9 DIABETES EDUCATOR JI Diabetes Educ. PD NOV-DEC PY 2006 VL 32 IS 6 BP 910 EP 917 DI 10.1177/0145721706294259 PG 8 WC Endocrinology & Metabolism; Public, Environmental & Occupational Health SC Endocrinology & Metabolism; Public, Environmental & Occupational Health GA 112VP UT WOS:000242556100008 PM 17102158 ER PT J AU Nathan, DM Buse, JB Davidson, MB Heine, RJ Holman, RR Sherwin, R Zinman, B AF Nathan, D. M. Buse, J. B. Davidson, M. B. Heine, R. J. Holman, R. R. Sherwin, R. Zinman, B. TI Management of hyperglycaemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy (vol 49, pg 2816, 2006) SO DIABETOLOGIA LA English DT Correction C1 Massachusetts Gen Hosp, Ctr Diabet, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ N Carolina, Sch Med, Chapel Hill, NC USA. Charles R Drew Univ Med & Sci, Clin Trials Unit, Los Angeles, CA 90059 USA. Vrije Univ Amsterdam, Med Ctr, Ctr Diabet, Amsterdam, Netherlands. Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Diabet Trials Unit, Oxford OX1 2JD, England. Yale Univ, Sch Med, Dept Internal Med & Endocrinol, New Haven, CT 06520 USA. Univ Toronto, Mt Sinai Hosp, Dept Endocrinol, Toronto, ON M5G 1X5, Canada. Univ Toronto, Mt Sinai Hosp, Dept Metab, Toronto, ON M5G 1X5, Canada. RP Nathan, DM (reprint author), Massachusetts Gen Hosp, Ctr Diabet, Boston, MA 02114 USA. EM dnathan@partners.org NR 1 TC 20 Z9 20 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 NOV PY 2006 VL 49 IS 11 BP 2816 EP 2818 DI 10.1007/s00125-006-0415-0 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 099FL UT WOS:000241578600050 ER PT J AU Reger, MA Craft, S AF Reger, Mark A. Craft, Suzanne TI Intranasal insulin administration: A method for dissociating central and peripheral effects of insulin SO DRUGS OF TODAY LA English DT Article ID CENTRAL-NERVOUS-SYSTEM; APOLIPOPROTEIN-E GENOTYPE; OBESE ZUCKER RATS; GROWTH-FACTOR-I; CEREBRAL GLUCOSE-UTILIZATION; RECEPTOR SUBSTRATE-1 IRS-1; AMYLOID PRECURSOR PROTEIN; FOOD-INTAKE; CEREBROSPINAL-FLUID; ALZHEIMERS-DISEASE AB Animal studies have demonstrated the effects of insulin on central nervous system (CNS) functions such as cognition and control of adiposity, but human studies of insulin's CNS effects are more difficult to interpret. Peripheral insulin administration, which increases CNS insulin levels, is associated with increased insulin-stimulated glucose disposal and the release of counter-regulatory hormones - events that can confound CNS results. However, intranasal insulin administration results in direct insulin transport from the nasal cavity to the CNS via intraneuronal and extraneuronal pathways. Recent studies from independent groups of investigators have demonstrated functional, cognitive and adiposity changes following acute and chronic intranasal administration in humans. Available evidence suggests that intranasal insulin administration is safe in humans. Thus, this approach may provide the opportunity to dissociate the central and peripheral effects of insulin. Furthermore, intranasal insulin administration may offer a novel treatment strategy for disorders associated with central insulin abnormalities, such as diabetes and neurodegenerative diseases. (c) 2006 Prous Science. All rights reserved. C1 Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA USA. Univ Washington, Sch Med, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Craft, S (reprint author), 1660 S Columbian Way,GRECC S182, Seattle, WA 98108 USA. EM scraft@u.washington.edu NR 98 TC 27 Z9 27 U1 3 U2 9 PU PROUS SCIENCE, SA PI BARCELONA PA PO BOX 540, PROVENZA 388, 08025 BARCELONA, SPAIN SN 1699-3993 J9 DRUGS TODAY JI Drugs Today PD NOV PY 2006 VL 42 IS 11 BP 729 EP 739 DI 10.1358/dot.2006.42.11.1007675 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 122IO UT WOS:000243219600005 PM 17171192 ER PT J AU Zhu, A Holalkere, N Norden-Zfoni, A Muzikansky, A Heymach, J Sahani, D AF Zhu, A. Holalkere, N. Norden-Zfoni, A. Muzikansky, A. Heymach, J. Sahani, D. TI Changes in computed tomography perfusion scan parameters and circulating endothelial cells following bevacizumab administration in patients with advanced hepatocellular carcinoma SO EJC SUPPLEMENTS LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Harvard Med Sch, Boston, MA USA. Childrens Hosp, Harvard Med Sch, Boston, MA USA. MD Anderson Canc Ctr, Houston, TX USA. NR 0 TC 1 Z9 1 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD NOV PY 2006 VL 4 IS 12 MA 54 BP 20 EP 21 DI 10.1016/S1359-6349(06)70060-X PG 2 WC Oncology SC Oncology GA 114TM UT WOS:000242688500053 ER PT J AU Davis, DW McConkey, DJ Heymach, JV Desai, J George, S DePrimo, SE Bello, CL Baum, CM Demetri, GD AF Davis, D. W. McConkey, D. J. Heymach, J. V. Desai, J. George, S. DePrimo, S. E. Bello, C. L. Baum, C. M. Demetri, G. D. TI Correlation of receptor tyrosine kinase (RTK) activity and apoptosis with response to sunitinib treatment in patients with gastrointestinal stromal tumor (GIST) SO EJC SUPPLEMENTS LA English DT Meeting Abstract C1 ApoCell Inc, Houston, TX USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Pfizer Global Res & Dev, La Jolla, CA USA. NR 0 TC 1 Z9 1 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 NOV PY 2006 VL 4 IS 12 MA 57 BP 21 EP 22 DI 10.1016/S1359-6349(06)70063-5 PG 2 WC Oncology SC Oncology GA 114TM UT WOS:000242688500056 ER PT J AU Mathew, P Thall, PF Wen, S Horne, E Johnson, M Oh, WK Morris, MJ Logothetis, CJ Fidler, IJ Bucana, C AF Mathew, P. Thall, P. F. Wen, S. Horne, E. Johnson, M. Oh, W. K. Morris, M. J. Logothetis, C. J. Fidler, I. J. Bucana, C. TI Correlative results of in-vivo monitoring of platelet-derived growth factor receptor (PDGFR) activation status in a randomized placebo-controlled trial of docetaxel +/- imatinib in castration-resistant prostate cancer (CRPC) and bone metastases (BM) 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. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 NR 0 TC 1 Z9 1 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 NOV PY 2006 VL 4 IS 12 MA 79 BP 28 EP 28 DI 10.1016/S1359-6349(06)70085-4 PG 1 WC Oncology SC Oncology GA 114TM UT WOS:000242688500078 ER PT J AU Stiede, K Eder, J Anthony, S Conkling, P Fayad, L Petrylak, D Sausville, E Verschraegen, C Bhat, G AF Stiede, K. Eder, J. Anthony, S. Conkling, P. Fayad, L. Petrylak, D. Sausville, E. Verschraegen, C. Bhat, G. TI Phase I dose escalation safety/tolerance study of PPI-2458 in subjects with Non-Hodgkin's lymphoma or solid tumors SO EJC SUPPLEMENTS LA English DT Meeting Abstract C1 PRAECIS Pharmaceut Inc, Waltham, MA USA. Dana Farber Canc Inst, Phase Clin Director 1, Boston, MA 02115 USA. US Oncol, Canc Care NW, Spokane, WA USA. US Oncol, Virginia Oncol Associates, Norfolk, VA USA. Univ Texas, MD Anderson Canc Inst, Houston, TX USA. Columbia Presbyterian Med Ctr, New York, NY 10032 USA. Univ Maryland, Baltimore, MD 21201 USA. Univ New Mexico, Albuquerque, NM 87131 USA. NR 0 TC 1 Z9 1 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 NOV PY 2006 VL 4 IS 12 MA 139 BP 45 EP 45 DI 10.1016/S1359-6349(06)70145-8 PG 1 WC Oncology SC Oncology GA 114TM UT WOS:000242688500138 ER PT J AU Cusack, J Wang, F Sloss, C Lu, R Xia, L AF Cusack, J. Wang, F. Sloss, C. Lu, R. Xia, L. TI EGFR activation and ERK survival signaling is triggered by proteasome inhibitors: implications for combining proteasome inhibitors with EGFR inhibitors SO EJC SUPPLEMENTS LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Harvard Med Sch, Boston, MA 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 NOV PY 2006 VL 4 IS 12 MA 179 BP 56 EP 56 DI 10.1016/S1359-6349(06)70184-7 PG 1 WC Oncology SC Oncology GA 114TM UT WOS:000242688500177 ER PT J AU Gordon, MS Eder, JP Mendelson, DS Wasserman, E Sutherland, W Kawabe, T Shapiro, GI AF Gordon, M. S. Eder, J. P. Mendelson, D. S. Wasserman, E. Sutherland, W. Kawabe, T. Shapiro, G. I. TI CBP501, a novel cell cycle G2 checkpoint abrogator. Preliminary results of the initial phase I and pharmacokinetic (PK)/pharmacodynamic (PD) study in patients (pts) with advanced solid tumors SO EJC SUPPLEMENTS LA English DT Meeting Abstract C1 Premiere Oncol, Scottsdale, AZ USA. Dana Farber Canc Inst, Boston, MA USA. CAC Oncol, San Antonio, TX USA. CAC Oncol, Le Kremlin Bicetre, France. CanBas Co Ltd, Numazu, Japan. 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 NOV PY 2006 VL 4 IS 12 MA 346 BP 108 EP 108 DI 10.1016/S1359-6349(06)70351-2 PG 1 WC Oncology SC Oncology GA 114TM UT WOS:000242688500342 ER PT J AU Lassen, U Sorensen, M De Bono, JS Molife, R Vidal, L Settatree, S Seiden, MV Li, SX Jensen, PB AF Lassen, U. Sorensen, M. De Bono, J. S. Molife, R. Vidal, L. Settatree, S. Seiden, M. V. Li, S. X. Jensen, P. B. TI A phase I safety, pharmacokinetic and pharmacodynamic study of intravenously administered PXD101 plus carboplatin or paclitaxel or both in patients with advanced solid tumors SO EJC SUPPLEMENTS LA English DT Meeting Abstract C1 Rigshosp, Dept Oncol 5073, DK-2100 Copenhagen, Denmark. Rigshosp, Dept Oncol, DK-2100 Copenhagen, Denmark. Royal Marsden NHS Trust, Drug Dev Unit, Sutton, Surrey, England. Massachusetts Gen Hosp, Div Med Oncol, Boston, MA 02114 USA. CuraGen Corp, Branford, CT USA. TopoTarget, Copenhagen, Denmark. 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 NOV PY 2006 VL 4 IS 12 MA 357 BP 111 EP 111 DI 10.1016/S1359-6349(06)70362-7 PG 1 WC Oncology SC Oncology GA 114TM UT WOS:000242688500353 ER PT J AU Gross, ME Amato, RJ Mushtaq, M Wilding, G Bubley, G Trudeau, C Rivera, VM Bedrosian, CL Agus, DB AF Gross, M. E. Amato, R. J. Mushtaq, M. Wilding, G. Bubley, G. Trudeau, C. Rivera, V. M. Bedrosian, C. L. Agus, D. B. TI A phase 2 trial of AP23573, an mTOR inhibitor, in patients (pts) with taxane-resistant androgen-independent prostate cancer (AIPC) SO EJC SUPPLEMENTS LA English DT Meeting Abstract C1 Cedars Sinai Med Ctr, Louis Warschaw Prostate Canc Ctr, Los Angeles, CA 90048 USA. Methodist Hosp, Res Inst, Genitourinary Oncol Program, Houston, TX 77030 USA. Univ Wisconsin, Ctr Comprehens Canc, Madison, WI USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Dana Farber Partners Canc Care, Boston, MA USA. ARIAD Pharmaceut Inc, Cambridge, MA 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 NOV PY 2006 VL 4 IS 12 MA 362 BP 112 EP 112 DI 10.1016/S1359-6349(06)70367-6 PG 1 WC Oncology SC Oncology GA 114TM UT WOS:000242688500358 ER PT J AU Morgan, J Demetri, G Wang, D MacPherson, I LoRusso, P van den Abbeele, A Brunton, V Luo, R Voi, M Evans, T AF Morgan, J. Demetri, G. Wang, D. MacPherson, I. LoRusso, P. van den Abbeele, A. Brunton, V. Luo, R. Voi, M. Evans, T. TI A Phase I Study of dasatinib, a SRC and multi-kinase inhibitor, in patients (pts) with GIST and other solid tumors SO EJC SUPPLEMENTS LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Karmanos Canc Inst, Detroit, MI USA. Univ Glasgow, Beatson Oncol Ctr, Glasgow, Lanark, Scotland. Bristol Myers Squibb Co, Wallingford, CT 06492 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 NOV PY 2006 VL 4 IS 12 MA 383 BP 118 EP 118 DI 10.1016/S1359-6349(06)70388-3 PG 1 WC Oncology SC Oncology GA 114TM UT WOS:000242688500379 ER PT J AU Leong, CO Vidnovic, N Carney, EE Sgroi, DC Ellisen, LW AF Leong, C. O. Vidnovic, N. Carney, E. E. Sgroi, D. C. Ellisen, L. W. TI Targeting p53-independent apoptosis in refractory breast cancers SO EJC SUPPLEMENTS LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. Massachusetts Gen Hosp, Dept Pathol, 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 NOV PY 2006 VL 4 IS 12 MA 385 BP 119 EP 119 DI 10.1016/S1359-6349(06)70390-1 PG 1 WC Oncology SC Oncology GA 114TM UT WOS:000242688500381 ER PT J AU LoRusso, P Appleman, L Zhu, A Shapiro, G Fox, L Wolanski, A Hitchcock-Bryan, S Malburg, L Eder, J AF LoRusso, P. Appleman, L. Zhu, A. Shapiro, G. Fox, L. Wolanski, A. Hitchcock-Bryan, S. Malburg, L. Eder, J. TI Pharmacodynamics (pd) of XL880, a novel spectrum selective kinase inhibitor (SSKI), administered orally to patients (pts) with advanced solid tumors (AST) SO EJC SUPPLEMENTS LA English DT Meeting Abstract C1 Wayne State Univ, Detroit, MI USA. Dana Farber Harvard Canc Inst, Boston, MA USA. NR 0 TC 1 Z9 1 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 NOV PY 2006 VL 4 IS 12 MA 404 BP 124 EP 124 DI 10.1016/S1359-6349(06)70409-8 PG 1 WC Oncology SC Oncology GA 114TM UT WOS:000242688500400 ER PT J AU Sepulveda, M Gomez, L Garza, J Sidransky, D Demetri, G Rowinsky, E Takimoto, C Wick, M AF Sepulveda, M. Gomez, L. Garza, J. Sidransky, D. Demetri, G. Rowinsky, E. Takimoto, C. Wick, M. TI Establishment and in vivo evaluation of two human sarcoma xenograft models: results of tumor growth and chemotherapy sensitivity in models of mesenchymal chondrosarcoma (MCS) and leiomyosarcoma (ILMS) SO EJC SUPPLEMENTS LA English DT Meeting Abstract C1 CTRC, Inst Drug Dev, San Antonio, TX USA. Johns Hopkins Univ, Baltimore, MD USA. Dana Farber Canc Inst, Harvard Med Sch, Boston, MA USA. ImClone Syst Inc, Branchburg, NJ USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD NOV PY 2006 VL 4 IS 12 MA 406 BP 125 EP 125 DI 10.1016/S1359-6349(06)70411-6 PG 1 WC Oncology SC Oncology GA 114TM UT WOS:000242688500402 ER PT J AU Sawai, A Greulich, H Ye, Q Sellers, W Rosen, N Solit, D AF Sawai, A. Greulich, H. Ye, Q. Sellers, W. Rosen, N. Solit, D. TI Inhibition of Hsp90 function downregulates EGFR and sensitizes EGFR-mutant xenografts to paclitaxel SO EJC SUPPLEMENTS LA English DT Meeting Abstract C1 Mem Sloan Kettering Canc Ctr, New York, NY USA. Dana Farber Canc Inst, Boston, MA 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 NOV PY 2006 VL 4 IS 12 MA 543 BP 165 EP 165 DI 10.1016/S1359-6349(06)70548-1 PG 1 WC Oncology SC Oncology GA 114TM UT WOS:000242688500538 ER PT J AU Phung, I Hochman, M Perruzzi, C Eyiah-Mensah, G Walsh, K Mihm, M Benjamin, L AF Phung, I. Hochman, M. Perruzzi, C. Eyiah-Mensah, G. Walsh, K. Mihm, M. Benjamin, L. TI Hemangioma is induced by sustained Akt signaling and inhibited by rapamycin SO EJC SUPPLEMENTS LA English DT Meeting Abstract C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Facial Surg Ctr, Charleston, SC USA. Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 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 NOV PY 2006 VL 4 IS 12 MA 551 BP 167 EP 167 PG 1 WC Oncology SC Oncology GA 114TM UT WOS:000242688500546 ER PT J AU Demetri, GD George, S Morgan, JA van den Abbeele, A Quigley, MT Fletcher, JA Normandt, E Patterson, J Adams, J Grayzel, D AF Demetri, G. D. George, S. Morgan, J. A. van den Abbeele, A. Quigley, M. T. Fletcher, J. A. Normandt, E. Patterson, J. Adams, J. Grayzel, D. TI Overcoming resistance to tyrosine kinase inhibitors (TKIs) through inhibition of Heat Shock Protein 90 (Hsp90) chaperone function in patients with metastatic GIST: results of a Phase I Trial of IPI-504, a water-soluble Hsp90 inhibitor SO EJC SUPPLEMENTS LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Ludwig Ctr, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA USA. Infinity Pharmaceut, Cambridge, MA USA. NR 0 TC 6 Z9 6 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 NOV PY 2006 VL 4 IS 12 MA 570 BP 173 EP 173 DI 10.1016/S1359-6349(06)70575-4 PG 1 WC Oncology SC Oncology GA 114TM UT WOS:000242688500565 ER PT J AU Davis, I Coxon, A Goldberg, J Burgess, T Fisher, D AF Davis, I. Coxon, A. Goldberg, J. Burgess, T. Fisher, D. TI Identification of the receptor tyrosine kinase c-Met and its ligand, HGF, as therapeutic targets in clear cell sarcoma SO EJC SUPPLEMENTS LA English DT Meeting Abstract C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Amgen Inc, Thousand Oaks, CA 91320 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 NOV PY 2006 VL 4 IS 12 MA 620 BP 187 EP 187 DI 10.1016/S1359-6349(06)70625-5 PG 1 WC Oncology SC Oncology GA 114TM UT WOS:000242688500615 ER PT J AU Morris, DM Gordon, JA AF Morris, David M. Gordon, James A. TI The role of the emergency department in the care of homeless and disadvantaged populations SO EMERGENCY MEDICINE CLINICS OF NORTH AMERICA LA English DT Article ID NEW-YORK-CITY; RISK-FACTORS; 5-YEAR PREVALENCE; UNITED-STATES; LOS-ANGELES; HEALTH; ADULTS; CHILDREN; MORTALITY; SERVICES AB Emergency departments (EDs) provide the only universal health care accessible to the general public in the United States, with well over 100 million patient visits per year [1,2]. Operating at the critical interface between the hospital and its community, EDs are designed to meet the demands of all patients. Whereas the specific needs of each community will vary, the fundamental approach to delivering emergency care remains the same-dedicated health professionals work 24 hours a day, 7 days a week to provide care to all patients, regardless of social circumstance. Because the ED functions as the ultimate health care "safety net," it can have a critical impact on homeless and other disadvantaged populations [3]. This chapter will review the epidemiology of social deprivation among ED patients, with a particular focus on understanding the nature of homelessness. It will then explore the value of an integrated approach to socio-medical care in the ED, and highlight successful ED-based approaches. C1 Framingham Union Hosp, Dept Emergency Med, Metrowest Med Ctr, Framingham, MA 01702 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA 02114 USA. RP Morris, DM (reprint author), Framingham Union Hosp, Dept Emergency Med, Metrowest Med Ctr, Framingham, MA 01702 USA. EM DMorris@quantech.net NR 58 TC 11 Z9 11 U1 0 U2 5 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0733-8627 J9 EMERG MED CLIN N AM JI Emerg. Med. Clin. N. Am. PD NOV PY 2006 VL 24 IS 4 BP 839 EP + DI 10.1016/j.emc.2006.06.011 PG 11 WC Emergency Medicine SC Emergency Medicine GA 091XV UT WOS:000241062500005 PM 16982342 ER PT J AU Kang, JH Irizarry, MC Grodstein, F AF Kang, Jae Hee Irizarry, Michael C. Grodstein, Francine TI Prospective study of plasma folate, vitamin B-12, and cognitive function and decline SO EPIDEMIOLOGY LA English DT Article ID ALZHEIMER-DISEASE; SERUM VITAMIN-B-12; FOLIC-ACID; APOLIPOPROTEIN-E; BREAST-CANCER; DNA-REPAIR; OLD-AGE; HOMOCYSTEINE; POPULATION; DEMENTIA AB Background: The relation between B vitamins and cognitive decline is controversial. In this study, we explored the association of plasma folate and vitamin 13, with cognitive function measured approximately 10 years later. Methods: We determined plasma folate and vitamin 13, levels from blood samples collected in 1989 to 1990 and initially evaluated cognition in 1995 to 2001 among 635 women, age 70+ years, from the Nurses' Health Study. In a subset of 391, 3 repeated cognitive tests were completed for evaluation of cognitive decline over 4 years; repeated testing is ongoing for the remaining women. Our primary outcome was a global composite score of 6 neuropsychologic tests administered by telephone. We used linear regression models to estimate multivariable-adjusted mean cognitive performance across quartiles of the vitamins and longitudinal models for cognitive decline. Results: Higher vitamin levels were not associated with either initial cognitive performance or subsequent cognitive decline. Mean difference in initial global score for top versus bottom quartiles was 0.06 standard units for folate (95% confidence interval [CI] = -0.10 to 0.22) and 0.15 units for vitamin 13, (0.00 to 0.31). There were no dose-response trends for either nutrient. Women with high levels of both nutrients initially performed better than women low in both nutrients (global score, mean difference = 0.34; 95% CI = 0.05 to 0.62); this association did not hold for subsequent cognitive decline. Conclusions: Combined B vitamin deficiency may be associated with impaired cognition, but in these healthy, well-nourished women, plasma folate and vitamin B-12 were not related to cognitive function. C1 Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Kang, JH (reprint author), Channing Labs, 181 Longwood Ave, Boston, MA 02115 USA. EM nhjhk@channing.harvard.edu FU NCI NIH HHS [CA49449, CA40356]; NIA NIH HHS [AG023860, AG15424] NR 43 TC 25 Z9 26 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2006 VL 17 IS 6 BP 650 EP 657 DI 10.1097/01.ede.0000239727.59575.da PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 096VV UT WOS:000241405800010 PM 17028506 ER PT J AU Hauser, R Meeker, JD Duty, S Silva, MJ Calafat, AM AF Hauser, Russ Meeker, John D. Duty, Susan Silva, Manori J. Calafat, Antonia M. TI Altered semen quality in relation to urinary concentrations of phthalate monoester and oxidative metabolites SO EPIDEMIOLOGY LA English DT Article ID TANDEM MASS-SPECTROMETRY; HUMAN EXPOSURE ASSESSMENT; DEUTERIUM-LABELED DEHP; DI(2-ETHYLHEXYL) PHTHALATE; TESTICULAR TOXICITY; DI-(2-ETHYLHEXYL) PHTHALATE; QUANTITATIVE DETECTION; NEONATAL-RATS; BIOMARKERS; DISPOSITION AB Background: Phthalates are multifunctional chemicals used in a variety of consumer, medical, and personal care products. Previously, we reported dose-response associations of decreased semen quality with urinary concentrations of monobutyl phthalate (MBP) and monobenzyl (MBzP) phthalate, which are metabolites of dibutyl phthalate and butylbenzyl phthalate, respectively. The present study extends our work in a larger sample of men and includes measurements of di(2-ethylhexyl) phthalate (DEHP) oxidative metabolites. Methods: Between January 2000 and May 2004, we recruited 463 male partners of subfertile couples who presented for semen analysis to the Massachusetts General Hospital. Semen parameters were dichotomized based on World Health Organization reference values for sperm concentration (<20 million/mL) and motility (<50% motile) and the Tygerberg Kruger Strict criteria for morphology (<4% normal). The comparison group was men with all 3 semen parameters above the reference values. In a single spot urine sample from each man, phthalate metabolites were measured using solid- phase extraction coupled to high-performance liquid chromatography isotope-dilution tandem mass spectrometry. Results: There were dose-response relationships of MBP with low sperm concentration (odds ratio per quartile adjusted for age, abstinence time, and smoking status = 1.00, 3.1, 2.5, 3.3; P for trend = 0.04) and motility (1.0, 1.5, 1.5, 1.8; P for trend = 0.04). There was suggestive evidence of an association between the highest MBzP quartile and low sperm concentration (1.00, 1.1, 1.1, 1.9; P for trend = 0.13). There were no relationships of monoethyl phthalate, monomethyl phthalate, and the DEHP metabolites with these semen parameters. Conclusion: The present study confirms previous results on the relationship of altered semen quality with exposure to MBP at general population levels. We did not find associations between semen parameters and 3 DEHP metabolites. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Publ Hlth, Boston, MA 02115 USA. Simmons Coll, Boston, MA 02115 USA. Ctr Dis Control & Prevent, Atlanta, GA USA. RP Hauser, R (reprint author), Harvard Univ, Sch Publ Hlth, Occupat Hlth Program, Bldg 1,Room 1405,665 Huntington Ave, Boston, MA 02115 USA. EM rhauser@hohp.harvard.edu OI Meeker, John/0000-0001-8357-5085 FU NIEHS NIH HHS [ES09718, T32 ES07069, ES00002] NR 44 TC 205 Z9 218 U1 7 U2 39 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2006 VL 17 IS 6 BP 682 EP 691 DI 10.1097/01.ede.0000235996.89953.d7 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 096VV UT WOS:000241405800014 PM 17003688 ER PT J AU Hart, JE Laden, F Smith, TJ Garshick, E AF Hart, J. E. Laden, F. Smith, T. J. Garshick, E. TI Chronic obstructive pulmonary disease mortality in a retrospective cohort of diesel-exposed railroad workers SO EPIDEMIOLOGY LA English DT Meeting Abstract CT ISEE/ISEA 2006 Conference CY 2006 CL Paris, FRANCE SP ISEE, ISEA C1 Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Harvard Med Sch, Harvard Sch Publ Hlth, Dept Environm Hlth, Exposure Epidemiol & Risk Program, Boston, MA USA. Harvard Sch Publ Hlth, Dept Environm Hlth, Exposure Epidemiol & Risk Program, Boston, MA USA. VA Boston Healthcare Syst, Boston, MA USA. Brigham & Womens Hosp, Harvard Med Sch, Channing Lab, 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 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2006 VL 17 IS 6 SU S BP S187 EP S187 DI 10.1097/00001648-200611001-00473 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 097JL UT WOS:000241443401002 ER PT J AU Wang, F Schwartz, J Hersh, C Kelsey, K Wright, R Spiro, A Sparrow, D Hu, H AF Wang, F. Schwartz, J. Hersh, C. Kelsey, K. Wright, R. Spiro, A. Sparrow, D. Hu, H. TI Modifying effects of the glutathione S-transferase polymorphisms on the association between lead burden and cognitive function SO EPIDEMIOLOGY LA English DT Meeting Abstract CT ISEE/ISEA 2006 Conference CY 2006 CL Paris, FRANCE SP ISEE, ISEA C1 Harvard Sch Publ Hlth, Dept Environm Hlth, Boston, MA USA. Brigham & Womens Hosp, Harvard Med Sch, Channing Lab, Boston, MA 02115 USA. Harvard Sch Publ Hlth, Dept Genet & Complex Dis, Boston, MA USA. Childrens Hosp, Boston, MA 02115 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 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2006 VL 17 IS 6 SU S BP S347 EP S348 DI 10.1097/00001648-200611001-00921 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 097JL UT WOS:000241443401450 ER PT J AU Gibson, WJ Gibson, M AF Gibson, William J. Gibson, Michael TI The association of impaired myocardial perfusion and monocytosis with late recovery of left ventricular function following primary percutaneous coronary intervention SO EUROPEAN HEART JOURNAL LA English DT Editorial Material ID BLOOD-CELL COUNT; INFARCTION; THROMBOLYSIS; OUTCOMES C1 MIT, Boston, MA USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. RP Gibson, M (reprint author), TIMI, Data Coordinating Ctr, 350 Longwood Ave,1st Floor, Boston, MA 02115 USA. EM mgibson@timi.org NR 7 TC 2 Z9 2 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD NOV PY 2006 VL 27 IS 21 BP 2487 EP 2488 DI 10.1093/eurheartj/ehl191 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 099XE UT WOS:000241629800002 PM 17000630 ER PT J AU Eurlings, LW Januzzi, JL Pinto, YM AF Eurlings, Luc W. Januzzi, James L. Pinto, Yigal M. TI Is acute heart failure a highly prevalent orphan disease? SO EUROPEAN HEART JOURNAL LA English DT Editorial Material ID QUALITY-OF-CARE; SURVEY PROGRAM; DIAGNOSIS; PROGNOSIS; MORTALITY; EUROPE C1 Univ Hosp Maastricht, Dept Cardiol, NL-6202 AZ Maastricht, Netherlands. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. RP Pinto, YM (reprint author), Univ Hosp Maastricht, Dept Cardiol, P Debyelaan 25,POB 5800, NL-6202 AZ Maastricht, Netherlands. EM y.pinto@cardio.azm.nl NR 8 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD NOV PY 2006 VL 27 IS 22 BP 2619 EP 2620 DI 10.1093/eurheartj/ehl332 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 104JV UT WOS:000241955600004 PM 17060342 ER PT J AU Loeppky, JA Icenogle, MV Caprihan, A Melo, MFV Altobelli, SA AF Loeppky, Jack A. Icenogle, Milton V. Caprihan, Arvind Melo, Marcos F. Vidal Altobelli, Stephen A. TI CO2 rebreathing model in COPD: blood-to-gas equilibration SO EUROPEAN JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE body CO2 stores; buffering capacity; gas exchange; ventilatory response to CO2; ventilation/perfusion heterogeneity ID OBSTRUCTIVE PULMONARY-DISEASE; CHRONIC AIRWAYS OBSTRUCTION; ARTERIAL PCO2 DIFFERENCE; MOUTH OCCLUSION PRESSURE; CARBON-DIOXIDE; VENTILATORY RESPONSE; CHRONIC HYPERCAPNIA; CARDIAC-OUTPUT; ALVEOLAR; PATTERN AB Rebreathing in a closed system can be used to estimate mixed venous P-CO2 (P (v) over bar (CO2)) and cardiac output, but these estimates are affected by V-A/Q heterogeneity. The purpose of this study was to validate a mathematical model of CO2 exchange during CO2 rebreathing in 29 patients with chronic obstructive pulmonary disease (COPD), with baseline arterial P-CO2 (Pa-CO2) ranging from 28 to 60 mmHg. Rebreathing increased end-tidal P-CO2 (PETCO2) by 20 mmHg over 2.2 min. This model employed baseline values for inspired (bag) P-CO2; estimated P (v) over bar (CO2); distribution of ventilation and blood flow in one high V-A/Q and one low V-A/Q compartment, the ventilation increase and conservation of mass equations to simulate time courses of PICO2; PETCO2; P (v) over bar (CO2) and Pa-CO2 : Measured PICO2 and PETCO2 during rebreathing differed by an average (SEM) of 1.4 (0.4) mmHg from simulated values. By end of rebreathing, predicted P (v) over bar (CO2) was lower than measured and predicted Pa-CO2; indicating gas to blood CO2 flux. Estimates of the ventilatory response to CO2, quantified as the slope (S) of the ventilation increase versus PETCO2; were inversely related to gas-to-blood P-CO2 disequilibria due to V-A/Q heterogeneity and buffer capacity (BC), but not airflow limitation. S may be corrected for these artifacts to restore S as a more valid noninvasive index of central CO2 responsiveness. We conclude that a rebreathing model incorporating baseline V-A/Q heterogeneity and BC can simulate gas and blood PCO2 in patients with COPD, where V-A/Q variations are large and variable. C1 Vet Adm Med Ctr, Cardiol Sect, Albuquerque, NM 87108 USA. New Mexico Resonance, Albuquerque, NM 87106 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Loeppky, JA (reprint author), Vet Adm Med Ctr, Cardiol Sect, 1501 San Pedro Dr SE, Albuquerque, NM 87108 USA. EM Loeppky@unm.edu NR 39 TC 2 Z9 2 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1439-6319 J9 EUR J APPL PHYSIOL JI Eur. J. Appl. Physiol. PD NOV PY 2006 VL 98 IS 5 BP 450 EP 460 DI 10.1007/s00421-006-0288-4 PG 11 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 114HX UT WOS:000242658400002 PM 16960726 ER PT J AU Cerrato, F Shagoury, J Kralickova, M Dwyer, A Falardeau, J Ozata, M Van Vliet, G Bouloux, P Hall, JE Hayes, FJ Pitteloud, N Martin, KA Welt, C Seminara, SB AF Cerrato, Felecia Shagoury, Jenna Kralickova, Milena Dwyer, Andrew Falardeau, John Ozata, Metin Van Vliet, Guy Bouloux, Pierre Hall, Janet E. Hayes, Frances J. Pitteloud, Nelly Martin, Kathryn A. Welt, Corrine Seminara, Stephanie B. TI Coding sequence analysis of GNRHR and GPR54 in patients with congenital and adult-onset forms of hypogonadotropic hypogonadism SO EUROPEAN JOURNAL OF ENDOCRINOLOGY LA English DT Article; Proceedings Paper CT 4th Ferring Pharmaceuticals International Paediatric Endocrinology Symposium CY 2006 CL Paris, FRANCE SP Ferring Pharmaceut ID GONADOTROPIN-RELEASING-HORMONE; PITUITARY-GONADAL AXIS; KALLMANN-SYNDROME; LUTEINIZING-HORMONE; RECEPTOR MUTATIONS; KISS-1 PEPTIDE; GENE; DEFICIENCY; HETEROGENEITY; RAT AB Objective: To determine the frequency of rare nucleotide variants in GNRHR and GPR54 in a large cohort of probands (n=166) with normosmic idiopathic hypogonadotropic hypogonadism (nIHH), characterized by mode of inheritance, testicular volume, and presence or absence of endogenous LH pulsations. Methods: Whenever possible, probands answered detailed questionnaires, underwent full physical exams, and underwent q 10-min frequent blood sampling for LH. Exons segments for GNRHR and GPR54 were screened for mutations. Nucleotide changes were identified as rare variants if they occurred at less than 1% frequency in an ethnically matched control population. Results: Sixty-two percent of male probands were classified as sporadic, meaning that no other family members had delayed puberty or nIHH. In contrast, 61% of female probands were from familial pedigrees, with either autosomal dominant or autosomal recessive inheritance. Patients displayed a broad spectrum of disease severity based on testicular size and endogenous LH pulsations. Twenty-four rare variants were identified in GNRHR (within 15 probands) and seven rare variants in GPR54 (within five probands). Conclusions: Rare variants in GNRHR are more common than GPR54 in a nIHH population. C1 Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. GATA Haydarpasa Training Hosp, Dept Endocrinol, Istanbul, Turkey. Univ Montreal, Dept Pediat, Montreal, PQ H3C 3J7, Canada. Royal Free Hosp, Dept Endocrinol, London NW3 2QG, England. RP Seminara, SB (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, BHX 504,Fruit St, Boston, MA 02114 USA. EM sseminara@partners.org RI Dwyer, Andrew/D-8099-2012; PITTELOUD, Nelly/K-2709-2014; OI Dwyer, Andrew/0000-0002-7023-6794; Welt, Corrine/0000-0002-8219-5504 FU NCRR NIH HHS [M01-RR-01 066]; NICHD NIH HHS [R01 HD043341, U54 HD028138, U54-HD028138-16] NR 41 TC 44 Z9 47 U1 0 U2 3 PU BIO SCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0804-4643 J9 EUR J ENDOCRINOL JI Eur. J. Endocrinol. PD NOV PY 2006 VL 155 SU 1 BP S3 EP S10 DI 10.1530/eje.1.02235 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 113NR UT WOS:000242605100002 PM 17074994 ER PT J AU Maiss, J Prat, F Wiesnet, J Proeschel, A Matthes, K Peters, A Hahn, EG Sautereau, D Chaussade, S Hochberger, J AF Maiss, Juergen Prat, Frederic Wiesnet, Johannes Proeschel, Andreas Matthes, Kai Peters, Andrea Hahn, Eckhart G. Sautereau, Denis Chaussade, Stanislas Hochberger, Juergen TI The complementary Erlangen Active Simulator for Interventional Endoscopy training is superior to solely clinical education in endoscopic hemostasis - the French training project: a prospective trial SO EUROPEAN JOURNAL OF GASTROENTEROLOGY & HEPATOLOGY LA English DT Article; Proceedings Paper CT 11th United European Gastroenterology Week CY NOV 01-05, 2003 CL Madrid, SPAIN DE endoscopic hemostasis; endoscopy training; training; ulcer; bleeding; upper gastrointestinal bleeding; variceal bleeding ID GASTROINTESTINAL ENDOSCOPY; COLONOSCOPY AB Background The Erlangen Active Simulator for Interventional Endoscopy (EASIE) using ex-vivo porcine organs was introduced in 1997. The present study should analyze whether repeated EASIE simulator training in endoscopic hemostasis led to superior performance compared with a traditionally educated group. The results were compared with a similar project in New York. Methods Thirty-five French GI fellows were enrolled. Baseline skills evaluation was performed in four disciplines (manual skills, injection/coagulation, clip application and variceal ligation) using the compactEASIE-simulator equipped with an upper gastrointestinal organ package for bleeding simulation. The same, translated evaluation forms (from the prior New York project) were used. Subsequently, fellows were randomized into group A (n = 17, only clinical education) and group B (n = 18, additional three simulator trainings). Group B was trained the next day and after 4 and 7 months by experts of the French Society of Gastrointestinal Endoscopy. Both groups performed routine and emergency endoscopies at their home hospitals during the study period. Both groups were re-evaluated blindly after 9 months. Results The learning curve for group B showed a significant improvement in all disciplines (P < 0.004) whereas group A improved significantly in only two of four disciplines at blinded final evaluation (manual skills P = 0.02, injection/coagulation P = 0.013). The direct comparison of groups B and A at blinded final evaluation showed significantly superior ratings for group B in all disciplines (P < 0.006) and significantly shorter performance times in two disciplines (P = 0.016 each). The comparison with the similar 'New York project' revealed that preexisting differences in skills were adjusted by the training. Conclusion Complementary trainings (three workshops in 7 months) in endoscopic hemostasis using the compactEASIE improved skills compared with a solely clinical education. The results of the 'New York project' were confirmed and benefits were independent from the medical educational system. C1 Univ Erlangen Nurnberg, Dept Med 1, D-91054 Erlangen, Germany. Univ Erlangen Nurnberg, Dept Med Informat Biometry & Epidemiol, Erlangen, Germany. St Bernward Hosp, Dept Med 3, Hildesheim, Germany. Hop Cochin, Serv Hepatogastroenterol, Paris, France. CHU Dupuytren, Serv Hepatogastroenterol, Limoges, France. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Maiss, J (reprint author), Univ Erlangen Nurnberg, Dept Med 1, Ulmenweg 18, D-91054 Erlangen, Germany. EM juergen.maiss@med1.imed.uni-erlangen.de NR 20 TC 25 Z9 26 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0954-691X J9 EUR J GASTROEN HEPAT JI Eur. J. Gastroenterol. Hepatol. PD NOV PY 2006 VL 18 IS 11 BP 1217 EP 1225 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 128GL UT WOS:000243646100016 PM 17033444 ER PT J AU Wiltshire, S de Bakker, PIW Daly, MJ AF Wiltshire, Steven de Bakker, Paul I. W. Daly, Mark J. TI The value of gene-based selection of tag SNPs in genome-wide association studies SO EUROPEAN JOURNAL OF HUMAN GENETICS LA English DT Article DE tag SNP selection; association studies; linkage disequilibrium; evolutionarily conserved regions ID LINKAGE-DISEQUILIBRIUM; TAGGING SNPS; SEQUENCES; POWER AB Genome-wide association scans are rapidly becoming reality, but there is no present consensus regarding genotyping strategies to optimise the discovery of true genetic risk factors. For a given investment in genotyping, should tag SNPs be selected in a gene-centric manner, or instead, should coverage be optimised based on linkage disequilibrium alone? We explored this question using empirical data from the HapMap-ENCODE project, and we found that tags designed specifically to capture common variation in exonic and evolutionarily conserved regions provide good coverage for 15 - 30% of the total common variation (depending on the population sample studied), and yield genotype savings compared with an anonymous tagging approach that captures all common variation. However, the same number of tags based on linkage disequilibrium alone captures substantially more (30 - 46%) of the total common variation. Therefore, the best strategy depends crucially on the unknown degree to which functional variation resides in recognisable exons and evolutionarily conserved sequence. A hypothetical but reasonable scenario might be one in which trait-causing variation is equally distributed between exons plus conserved sequence, and the rest of the genome. In this scenario, our analysis suggests that a tagging approach that captures variation in exons and conserved sequence provides only modestly better coverage of putatively causal variation than does anonymous tagging. In HapMap CEU samples (with northern and western European ancestry), we observed roughly equivalent coverage for equal investment for both tagging strategies. C1 Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England. Massachusetts Gen Hosp, Dept Biol Mol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02138 USA. MIT, Cambridge, England. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Daly, MJ (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, 185 Cambridge St,CPZN 6818, Boston, MA 02114 USA. EM mjdaly@chgr.mgh.harvard.edu RI de Bakker, Paul/B-8730-2009 OI de Bakker, Paul/0000-0001-7735-7858 NR 18 TC 14 Z9 16 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 NOV PY 2006 VL 14 IS 11 BP 1209 EP 1214 DI 10.1038/sj.ejhg.5201678 PG 6 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 099FE UT WOS:000241577900011 PM 16804554 ER PT J AU Sartor, O AF Sartor, Oliver TI Eligard (R) 6: A new form of treatment for prostate cancer SO EUROPEAN UROLOGY SUPPLEMENTS LA English DT Article DE Atrigel; Eligard; leuprolide; luteinising hormone-releasing hormone agonist prolonged-release; formulation; prostate cancer ID THERAPY ONCOLOGY GROUP; UNFAVORABLE-PROGNOSIS CARCINOMA; SUBCUTANEOUS DELIVERY-SYSTEM; OPTIMIZING HORMONE-THERAPY; LEUPROLIDE ACETATE; RADIATION-THERAPY; ANDROGEN SUPPRESSION; DEFINITIVE RADIOTHERAPY; PELVIC LYMPHADENECTOMY; RADICAL PROSTATECTOMY AB Objectives: Luteinising hormone-releasing hormone (LHRH) agonists have become the mainstay for the treatment of advanced and metastatic prostate cancer (pCA) but are increasingly used in earlier stages of the disease for various indications. Eligard((R)) is a depot formulation of leuprolide acetate using the novel delivery system Atrigel((R)). Eligard 6 is the first and only LHRH agonist commercially available that extends treatment for 6 mo. Methods: This literature review evaluates the efficacy and tolerability of Eligard 6 and discusses its potential advantages and therapeutic applications. Results: In a 12-mo open-label multicentre study, Eligard 6 rapidly suppressed testosterone levels to < 50 ng/dl in 97% of patients and <= 20 ng/dl in 83% of patients. This was maintained during the course of the study; only one patient experienced a breakthrough testosterone escape. Eligard 6 had a comparable tolerability to the 1- and 3-mo formulations of Eligard. Hot flashes were the most common adverse event with the majority being of mild intensity. Eligard 6 offers practical advantages to patients and physicians in terms of convenience and patient comfort and has cost benefits for the health care system. Its ability to provide 6-mo testosterone suppression may be of particular interest in the (neo)adjuvant setting and/or in patients receiving intermittent therapy for biochemical failure after radical therapy. Conclusions: Eligard 6 is a new LHRH agonist formulation that provides testosterone control for 6 mo and offers physicians the ability to tailor the management of pCA to the lifestyles of their patients. (c) 2006 European Association of Urology. Published by Elsevier B.V. All rights reserved. C1 Harvard Univ, Lank Ctr GU Oncol, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Sartor, O (reprint author), Harvard Univ, Lank Ctr GU Oncol, Sch Med, Dana Farber Canc Inst, Dana 1230,44 Binney St, Boston, MA 02115 USA. EM oliver_sartor@dfci.harvard.edu NR 26 TC 9 Z9 9 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1569-9056 J9 EUR UROL SUPPL JI Eur. Urol. Suppl. PD NOV PY 2006 VL 5 IS 18 BP 905 EP 910 DI 10.1016/j.eursup.2006.08.006 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 101AI UT WOS:000241710900004 ER PT J AU Dor, FJMF Ramirez, ML Parmar, K Altman, EL Huang, CA Down, JD Cooper, DKC AF Dor, Frank J. M. F. Ramirez, Mario L. Parmar, Kalindi Altman, Erica L. Huang, Christene A. Down, Julian D. Cooper, David K. C. TI Primitive hematopoietic cell populations reside in the spleen: Studies in the pig, baboon, and human SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID BONE-MARROW-CELLS; STEM-CELLS; MINIATURE SWINE; MONOCLONAL-ANTIBODIES; C-KIT; ALLOGRAFT TOLERANCE; PROGENITOR CELLS; MIXED CHIMERISM; MATCHED DONOR; TRANSPLANTATION AB Objective. We previously observed high levels (> 40%) of multilineage hematopoietic cell chimerism following spleen transplantation across full MHC barriers in immunosuppressed miniature swine. We therefore investigated the spleen as a source of hematopoietic progenitor cells (HPCs). Materials and Methods. Specific cell-surface markers were used to identify HPCs in the spleen and bone marrow (BM) of young adult (n = 15) and fetal (n = 9) miniature swine by flow cytometry. Hoechst dye-effluxing side population (SP) cells were analyzed in adult spleen, BM, and blood for their expression of c-kit. Functional HPC activity of varying repopulation potential in vitro was investigated by the ability of spleens and BM to give rise to colony-forming units (CFUs) and cobblestone area-forming cells (CAFCs) in long-term stromal cultures. Studies were also carried out on baboon and human spleens and BM. Results. Spleen c-kit(+) cells co-expressed more lymphoid markers, but equal myeloid markers, when compared with BM c-kit(+) cells. BM and spleen both contained significant percentages of c-kit(+) SP cells. Although the frequency of early-forming CFUs in the spleen was only 0.1 to 1.3% of that in the BM, the frequency of CAFCs developing after 8 weeks in culture was comparable to that of BM. Secondary CFUs in long-term culture-initiating cell assays confirmed the presence of long-term repopulating cells at comparable frequencies in spleen and BM. Similar findings were found with regard to baboon and human spleen cells. Conclusion. The adult spleen is a relatively rich source of very primitive HPCs, possibly hematopoietic stem cells (HSCs), and may be of therapeutic value. (c) 2006 International Society for Experimental Hematology. Published by Elsevier Inc. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Transplantat Biol Res Ctr, Boston, MA 02115 USA. Erasmus MC, Dept Surg, Rotterdam, Netherlands. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Genetix Pharmaceut Inc, Cambridge, MA USA. RP Cooper, DKC (reprint author), Univ Pittsburgh, Med Ctr, Thomas E Starzl Transplantat Inst, Biomed Sci Tower E,Room E1550A,200 Lothrop St, Pittsburgh, PA 15261 USA. EM cooperdk@upmc.edu RI Dor, Frank/E-1032-2013 OI Dor, Frank/0000-0001-7845-3075 FU PHS HHS [1P01 A145897] NR 59 TC 26 Z9 26 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD NOV PY 2006 VL 34 IS 11 BP 1573 EP 1582 DI 10.1016/j.exphem.2006.06.016 PG 10 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 103VU UT WOS:000241915800015 PM 17046577 ER PT J AU Hadlock, T Sundback, C AF Hadlock, Tessa Sundback, Cathryn TI Biologically inspired approaches to drug delivery for nerve regeneration SO EXPERT OPINION ON BIOLOGICAL THERAPY LA English DT Review DE drug delivery; nerve regeneration; tissue engineering ID MAGNETICALLY ALIGNED COLLAGEN; GROWTH-FACTOR; SCHWANN-CELLS; SPINAL-CORD; GUIDANCE CHANNELS; NEURITE EXTENSION; PERIPHERAL-NERVES; GENE-TRANSFER; IN-VITRO; NEUROTROPHIC FACTORS AB As the biological processes governing nerve regeneration have become elucidated over the past decades, interest has developed in manipulating these processes to improve nerve regeneration. Drug delivery to the regenerating nerve has the potential for major clinical applications in neurodegenerative diseases, spinal cord injury and peripheral nerve injury or sacrifice. This article reviews the evolution of the field of drug delivery to the regenerating nerve, from simple local applications of neurotrophic agents in solution and osmotic pump delivery, to the existing approaches involving novel biomaterials and genetically manipulated cell populations. A discussion of the various known nerve growth-promoting agents, and the chemical considerations involved in their delivery, is included. A perspective on the role of tissue engineering approaches for nerve regeneration in the future is offered. C1 Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. Harvard Univ, Sch Med, Div Facial Plast & Reconstruct Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Ctr Regenerat Med, Boston, MA 02114 USA. RP Hadlock, T (reprint author), Massachusetts Eye & Ear Infirm, 243 Charles St, Boston, MA 02114 USA. EM csundback@partners.org NR 76 TC 9 Z9 9 U1 0 U2 4 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1471-2598 J9 EXPERT OPIN BIOL TH JI Expert Opin. Biol. Ther. PD NOV PY 2006 VL 6 IS 11 BP 1105 EP 1111 DI 10.1517/14712598.6.11.1105 PG 7 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 099UL UT WOS:000241621600004 PM 17049009 ER PT J AU Aperis, G Myriounis, N Spanakis, EK Mylonakis, E AF Aperis, George Myriounis, Nikolaos Spanakis, Elias K. Mylonakis, Eleftherios TI Developments in the treatment of candidiasis: more choices and new challenges SO EXPERT OPINION ON INVESTIGATIONAL DRUGS LA English DT Review DE anidulafungin; BAL4815; Candida; candidaemia; candidiasis; caspofungin; FK463; L-743872; LY303366; micafungin; MK-0991; posaconazole; SCH56592; UK-109496; voriconazole ID IN-VITRO ACTIVITIES; TRIAZOLE ANTIFUNGAL AGENTS; MURINE DISSEMINATED CANDIDIASIS; BLOOD-STREAM INFECTIONS; AMPHOTERICIN-B; ESOPHAGEAL CANDIDIASIS; DOUBLE-BLIND; FLUCONAZOLE-RESISTANT; INVASIVE CANDIDIASIS; VORICONAZOLE UK-109,496 AB The incidence of oesophageal candidiasis, candidaemia and disseminated candidiasis has increased dramatically. In addition to the amphotericin B formulations and fluconazole, the echinocandins anidulafungin, caspofungin and micafungin and the newer triazoles posaconazole and voriconazole are in the last stages of development and are becoming available for the management of candidiasis. This review presents these new agents and addresses their role in the treatment of candidiasis. All new antifungal agents exhibit potent activity against Candida spp. and echinocandins are fungicidal against most Candida spp. but appear to be less potent against certain species, such as Candida parapsilosis and C. guilliermondii. Systemic antifungal therapy can now be individualised based on the severity of the infection, comorbid conditions and the Candida spp. causing the infection. Studies are needed to investigate the possible development of resistance and the efficacy of these antifungal agents against the more resistant Candida spp. C1 Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Mylonakis, E (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Gray Jackson 504,55 Fruit St, Boston, MA 02114 USA. EM emylonakis@partners.org FU NIAID NIH HHS [K08 AI63084] NR 102 TC 37 Z9 42 U1 0 U2 7 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1354-3784 J9 EXPERT OPIN INV DRUG JI Expert Opin. Investig. Drugs PD NOV PY 2006 VL 15 IS 11 BP 1319 EP 1336 DI 10.1517/13543784.15.11.1319 PG 18 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 102DK UT WOS:000241791000004 PM 17040194 ER PT J AU Czibere, A Groll, F Aivado, M AF Czibere, Akos Groll, Franck Aivado, Manuel TI Perspectives of proteomics in acute myeloid leukemia SO EXPERT REVIEW OF ANTICANCER THERAPY LA English DT Review DE acute myeloid leukemia; biomarkers; protein mass spectrometry; protein profiling proteomics ID STEM-CELL TRANSPLANTATION; PROTEIN IDENTIFICATION TECHNOLOGY; DIMENSIONAL GEL-ELECTROPHORESIS; ACUTE LYMPHOBLASTIC-LEUKEMIA; CHRONIC MYELOGENOUS LEUKEMIA; TRANS-RETINOIC ACID; CODED AFFINITY TAGS; MASS-SPECTROMETRY; TYROSINE KINASE; 5-AZA-2'-DEOXYCYTIDINE DECITABINE AB Acute myeloid leukemia (AML) is a frequent hematological malignancy. Despite enormous therapeutic efforts that range from various cytotoxic agents to allogeneic stem cell transplantation, overall survival of patients with AML remains unsatisfying. The poor survival rates are mainly due to therapy-related mortality, failure of induction chemotherapy and early relapses. Therefore, novel therapeutic agents that are more efficient and better tolerated are eagerly sought after. For existing therapeutic strategies, there is a lack of markers that are capable of reliably predicting prognosis or the therapeutic response prior to treatment. There is hope that elucidation of the AML-specific proteome will prompt the discovery of novel therapeutic targets and biomarkers in AML. Modern mass-spectrometry instrumentation has acheived excellent performance in terms of sensitivity, resolution and mass accuracy; however, so far, the contribution of proteomics to the care of patients with AML is virtually zero. This might be partly because mass spectrometry instrumentation and protein fractionation still lack true high-throughput capabilities with highest levels of reproducibility, thus hampering large-scale translational studies with clinical samples. Since mass-spectrometry instruments are very intricate devices, their successful operation will hinge on the willingness and ability of mass-spectrometry experts and clinical researchers to adopt new views, learn from each other and cooperate in order to ultimately benefit the patient suffering from AML. This review highlights some clinical problems circumventing the treatment of patients with AML. Furthermore, it provides a brief overview of the technical background of standard proteomics approaches and describes opportunities, challenges and pitfalls of proteomic studies with regards to AML. C1 Univ Dusseldorf, Dept Hematol Oncol & Clin Immunol, D-40225 Dusseldorf, Germany. Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Harvard Inst Med, BIDMC Genom Ctr, Boston, MA 02115 USA. RP Czibere, A (reprint author), Univ Dusseldorf, Dept Hematol Oncol & Clin Immunol, Moorenstr 5, D-40225 Dusseldorf, Germany. EM aczibere@bidmc.harvard.edu; fgrall@bidmc.harvard.edu; maivado@bidmc.harvard.edu NR 99 TC 9 Z9 10 U1 0 U2 0 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7140 J9 EXPERT REV ANTICANC JI Expert Rev. Anticancer Ther PD NOV PY 2006 VL 6 IS 11 BP 1663 EP 1675 DI 10.1586/14737140.6.11.1663 PG 13 WC Oncology SC Oncology GA 116NO UT WOS:000242809800012 PM 17134369 ER PT J AU Wang, J Ho, L Zhao, Z Seror, I Humala, N Dickstein, DL Thiyagarajan, M Percival, SS Talcott, ST Pasinetti, GM AF Wang, Jun Ho, Lap Zhao, Zhong Seror, Ilana Humala, Nelson Dickstein, Dara L. Thiyagarajan, Meenakshisundaram Percival, Susan S. Talcott, Stephen T. Pasinetti, Giulio Maria TI Moderate consumption of Cabernet Sauvignon attenuates A beta neuropathology in a mouse model of Alzheimer's disease SO FASEB JOURNAL LA English DT Article DE APP; nonamyloidogenic; polyphenols; AD dementia ID AMYLOID PRECURSOR PROTEIN; COGNITIVE IMPAIRMENT; TRANSGENIC MICE; SENILE PLAQUES; DEMENTIA; WINE; ALCOHOL; ASSOCIATION; DEPOSITION; CLEAVAGE AB Recent studies suggest that moderate red wine consumption reduces the incidence of Alzheimer's disease (AD) clinical dementia. Using Tg2576 mice, which model AD-type amyloid beta-protein (A beta) neuropathology, we tested whether moderate consumption of the red wine Cabernet Sauvignon modulates AD-type neuropathology and cognitive deterioration. The wine used in the study was generated using Cabernet Sauvignon grapes from Fresno, California, and was delivered to Tg2576 in a final concentration of similar to 6% ethanol. We found that Cabernet Sauvignon significantly attenuated AD-type deterioration of spatial memory function and A beta neuropathology in Tg2576 mice relative to control Tg2576 mice that were treated with either a comparable amount of ethanol or water alone. Chemical analysis showed the Cabernet Sauvignon used in this study contains a very low content of resveratrol (0.2 mg/L), 10-fold lower than the minimal effective concentration shown to promote A beta clearance in vitro. Our studies suggest Cabernet Sauvignon exerts a beneficial effect by promoting nonamyloidogenic processing of amyloid precursor protein, which ultimately prevents the generation of A beta peptides. This study supports epidemiological evidence indicating that moderate wine consumption, within the range recommended by the FDA dietary guidelines of one drink per day for women and two for men, may help reduce the relative risk for AD clinical dementia. C1 CUNY Mt Sinai Sch Med, Dept Neurosci, New York, NY 10029 USA. CUNY Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. James J Peters VA Med Ctr, Geriatr Res & Clin Ctr, Bronx, NY USA. Univ Florida, Dept Food Sci & Human Nutr, Gainesville, FL USA. RP Pasinetti, GM (reprint author), CUNY Mt Sinai Sch Med, Dept Neurosci, 1 Gustave L Levy Pl, New York, NY 10029 USA. EM giulio.pasinetti@mssm.edu RI Dickstein, Dara/F-3036-2013 NR 34 TC 154 Z9 160 U1 3 U2 13 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD NOV PY 2006 VL 20 IS 13 BP 2313 EP 2320 DI 10.1096/fj.06-6281com PG 8 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 100XD UT WOS:000241702600016 PM 17077308 ER PT J AU Lee, J Kosaras, B Aleyasin, H Han, JA Park, DS Ratan, RR Kowall, NW Ferrante, RJ Lee, SW Ryu, H AF Lee, Junghee Kosaras, Bela Aleyasin, Hossein Han, Jeong A. Park, David S. Ratan, Rajiv R. Kowall, Neil W. Ferrante, Robert J. Lee, Sam W. Ryu, Hoon TI Role of cyclooxygenase-2 induction by transcription factor Sp1 and Sp3 in neuronal oxidative and DNA damage response SO FASEB JOURNAL LA English DT Article DE oxidative stress; neuronal survival ID ALZHEIMERS-DISEASE; CORTICAL-NEURONS; MESSENGER-RNA; LATE-PHASE; CEREBRAL-ISCHEMIA; CONSCIOUS RABBITS; BINDING PROTEIN; HUMAN BRAIN; C/EBP-BETA; RAT-BRAIN AB Cyclooxygenase-2 (COX-2) has been implicated in neuronal survival and death. However, the precise regulatory mechanisms involved in COX-2 function are unclear. In the present study we found that COX-2 is induced in response to glutathione depletion-induced oxidative stress in primary cortical neurons. Two proximal specific Sp1 and Sp3 binding sites are responsible for the COX-2 promoter activity under normal as well as oxidative stress conditions through enhanced Sp1 and Sp3 DNA binding activity. Site-directed mutagenesis confirmed that -268/-267 positions serve as specific Sp1 and Sp3 recognition sites under oxidative stress. Enforced expression of Sp1 and Sp3 using HSV vectors increased the promoter activity, transcription, and protein level of COX-2 in cortical neurons. The dominant negative form of Sp1 abrogated the oxidative stress-induced promoter activity and expression of COX-2. We also demonstrated that adenovirus-mediated COX-2 gene delivery protected neurons from DNA damage induced by oxidative, genotoxic, and excitotoxic stresses and by ischemic injury. Moreover, COX-2(-/-) cortical neurons were more susceptible to DNA damage-induced cell death. These results indicate that in primary neurons Sp1 and Sp3 play an essential role in the modulation of COX-2 transcription, which mediates neuronal homeostasis and survival by preventing DNA damage in response to neuronal stress. C1 VA Med Ctr, GRECC, Bedford, MA 01730 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Pathol, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. Beth Israel Deaconess Med Ctr, Dept Neurol, Boston, MA 02215 USA. Univ Ottawa, Ottawa Hlth Res Inst, Neurosci Res Program, Ottawa, ON, Canada. Harvard Univ, Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. Cornell Univ, Weill Med Coll, Dept Neurol, White Plains, NY USA. Burke Cornell Med Res Inst, White Plains, NY USA. RP Ryu, H (reprint author), VA Med Ctr, GRECC, 200 Springs Rd,Unit 182B, Bedford, MA 01730 USA. EM hoonryu@bu.edu RI Kowall, Neil/G-6364-2012; OI Kowall, Neil/0000-0002-6624-0213; Aleyasin, Hossein/0000-0002-0021-2586 FU NCI NIH HHS [CA097216, CA8521406]; NIA NIH HHS [P30 AG13846]; NINDS NIH HHS [NS52724-01, NS045806, NS045242] NR 44 TC 35 Z9 40 U1 1 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD NOV PY 2006 VL 20 IS 13 BP 2375 EP + DI 10.1096/fj.06-5957fje PG 13 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 100XD UT WOS:000241702600025 PM 17012241 ER PT J AU Bonkovsky, HL Naishadham, D Lambrecht, RW Chung, RT Hoefs, JC Nash, SR Rogers, TE Banner, BF Sterling, RK Donovan, JA Fontana, RJ Di Bisceglie, AM Ghany, MG Morishima, C AF Bonkovsky, Herbert L. Naishadham, Deepa Lambrecht, Richard W. Chung, Raymond T. Hoefs, John C. Nash, S. Russell Rogers, Thomas E. Banner, Barbara F. Sterling, Richard K. Donovan, John A. Fontana, Robert J. Di Bisceglie, Adrian M. Ghany, Marc G. Morishima, Chihiro CA HALT-C Trial Grp TI Roles of iron and HFE mutations on severity and response to therapy during retreatment of advanced chronic hepatitis C SO GASTROENTEROLOGY LA English DT Article ID INTERFERON-ALPHA THERAPY; CHRONIC VIRAL-HEPATITIS; LONG-TERM RESPONSE; CONTROLLED-TRIAL; SERUM IRON; HEREDITARY HEMOCHROMATOSIS; GENETIC HEMOCHROMATOSIS; LIVER-DISEASES; RISK-FACTORS; FIBROSIS AB Background & Aims: Iron overload may cause or contribute to hepatic injury and fibrosis. Mutations in the HFE gene may influence development or progression of chronic liver disease by increasing iron stores or modulating immune responses. The aim of this work was to assess the influence of HFE mutations and serum and hepatic measures of iron status on baseline features and response to lead-in therapy in subjects with advanced chronic hepatitis C enrolled in the Hepatitis C Anti-viral Long-term Treatment to prevent Cirrhosis (HALT-C) Trial. Methods: Entry criteria included an Ishak fibrosis score > 2 and lack of iron overload (Scheuer iron grade < 3+) according to local study pathologists. All baseline biopsy specimens were rescored by consensus of study pathologists, and detailed assessment of stainable iron was performed. Hepatic iron concentrations were measured on portions of 144 liver biopsy specimens. A total of 1051 out of 1145 subjects agreed to HFE mutational testing (C282Y, H63D, S65C). Results: Thirty-five percent carried at least one HFE gene mutation. There were no significant differences in the prevalence of HFE gene mutations among subjects with fibrosis (35.5%) versus cirrhosis (32.9%). Thirty-three percent of subjects had end-of-treatment and 16% sustained virologic responses. Presence of HFE mutations, in particular the H63D variation, was associated with increased end-of-treatment (40% vs 29%, P=.0078) and sustained virologic responses (20% with HFE mutation vs 14% sustained virologic response without HFE mutation; P=.009). Conclusions: Although HFE mutations (especially the most frequent H63D mutation) are associated with increased iron loading, they are also associated with increased sustained virologic responses in US patients with advanced chronic hepatitis C. C1 Univ Connecticut, Ctr Hlth, Dept Med, Farmington, CT 06030 USA. Univ Connecticut, Ctr Hlth, Dept Mol & Struct Biol, Farmington, CT 06030 USA. Univ Connecticut, Ctr Hlth, Dept Pharmacol, Farmington, CT 06030 USA. Univ Connecticut, Ctr Hlth, Liver Biliary Pancreat Ctr, Farmington, CT 06030 USA. New England Res Inst, Watertown, MA 02172 USA. Massachusetts Gen Hosp, Gastrointestinal Unit, Med Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA. Univ Calif Irvine, Div Gastroenterol, Irvine, CA USA. Univ Colorado, Dept Pathol, Denver, CO 80202 USA. Hlth Sci Ctr, Denver, CO 80202 USA. Univ Texas, SW Med Ctr, Dept Pathol, Dallas, TX 75216 USA. Univ Massachusetts, Med Ctr, Dept Pathol, Worcester, MA USA. Virginia Commonwealth Univ, Hepatol Sect, Med Ctr, Richmond, VA USA. Univ So Calif, Keck Sch Med, Div Gastrointestinal & Liver Dis, Los Angeles, CA USA. Univ Michigan, Med Ctr, Div Gastroenterol, Ann Arbor, MI 48109 USA. St Louis Univ, Sch Med, Div Gastroenterol & Hepatol, St Louis, MO 63103 USA. NIDDKD, Liver Dis Branch, Div Digest Dis & Nutr, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. RP Bonkovsky, HL (reprint author), Univ Connecticut, Ctr Hlth, Dept Med, 263 Farmington Ave,MC-1119, Farmington, CT 06030 USA. EM bonkovsky@uchc.edu FU NCRR NIH HHS [M01RR-01066, M01RR-00633, M01RR-00827, M01RR-00042, M01RR-00043, M01RR-00065, M01RR-00051, M01RR-06192]; NIDDK NIH HHS [N01-DK-9-2323, N01-DK-9-2326, N01-DK-9-2327, N01-DK-9-2322, N01-DK-9-2328, N01-DK-9-2320, N01-DK-9-2321, N01-DK-9-2319, N01-DK-92324, N01-DK-9-2318, N01-DK-9-2325] NR 60 TC 62 Z9 66 U1 0 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD NOV PY 2006 VL 131 IS 5 BP 1440 EP 1451 DI 10.1053/j.gastro.2006.08.036 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 108DR UT WOS:000242221000016 PM 17101320 ER PT J AU Lauwers, GY Chung, DC AF Lauwers, Gregory Y. Chung, Daniel C. TI The serrated polyp comes of age SO GASTROENTEROLOGY LA English DT Editorial Material ID NONPOLYPOSIS COLORECTAL-CANCER; HYPERPLASTIC POLYPS; MISMATCH-REPAIR; BRAF MUTATIONS; METHYLATION; ADENOMAS; GENETICS; HMLH1 C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pathol Dept,Gastrointestinal Pathol Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Chung, DC (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, GRJ 825, 50 Blossom St, Boston, MA 02114 USA. EM dchung@partners.org NR 20 TC 15 Z9 16 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD NOV PY 2006 VL 131 IS 5 BP 1631 EP 1634 DI 10.1053/j.gastro.2006.09.035 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 108DR UT WOS:000242221000033 PM 17067594 ER PT J AU El-Serag, HB Gilger, MA Shud, MD Rechardson, P Bancroft, J AF El-Serag, Hashem B. Gilger, Mark A. Shud, Mitchell D. Rechardson, Peter Bancroft, John TI The prevalence of suspected Barrett's esophagus in children and adolescents: a multicenter endoscopic study SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID GASTROESOPHAGEAL-REFLUX DISEASE AB Background: The prevalence of Barrett's esophagus (BE) in young individuals is unclear. Objective: To estimate the prevalence of suspected BE in children and adolescent patients undergoing endoscopy. Design: A retrospective cross-sectional study Setting: Prospectively collected data in the Pediatric Clinical Outcomes Research Initiative (PEDS-CORI) Patients: We identified patients younger than 20 years of age with suspected BE in the PEDS-CORI between 1999 and 2002; the corresponding histopathologic records were examined. Main Outcome Measurements: We analyzed the distribution of demographic and endoscopic risk factors for BE between cases and non-cases with and without suspected BE in bivariate and multivariable analyses. Results: We identified a total of 6731 patients who underwent upper endoscopy in 12 pediatric facilities. Only 17 patients had suspected BE (prevalence, 2.5 per 1000). Intestinal metaplasia was reported in only 9 of these patients (53%). Patients with suspected BE were older than patients without BE (median 14.7 vs 10.1 years; P =.011). Hiatus hernia was more commonly recorded in patients with suspected BE (11.8% vs 2.2%; P =.008). In a logistic regression model, both older age (odds ratio [OR] 1.13, 95% confidence interval [CI] 1.02-1.35) and hiatus hernia (OR 4.62, 95% CI 1.03-20.66) were independently associated with suspected BE. Conclusions: Endoscopically suspected BE is rare (< 0.25%) in children and adolescents. Older age and the presence of hiatus hernia are possible risk factors for BE in this group. Limitations: Lack of standardization for identifying and recording endoscopic landmarks. C1 Michael E DeBakey Vet Affairs Med Ctr 152, Dept Gastroenterol & Hlth Serv Res, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. Barbara Bush Childrens Hosp, Portland, ME USA. Phoenix Childrens Hosp, Phoenix, AZ USA. RP El-Serag, HB (reprint author), Michael E DeBakey Vet Affairs Med Ctr 152, Dept Gastroenterol & Hlth Serv Res, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM hasheme@bcm.tmc.edu FU NIDDK NIH HHS [R03 DK068148-01, R01-DK30144-21/23] NR 16 TC 20 Z9 21 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 EI 1097-6779 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD NOV PY 2006 VL 64 IS 5 BP 671 EP 675 DI 10.1016/j.gie.2006.03.010 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 099YR UT WOS:000241634300001 PM 17055854 ER PT J AU Graham, DY Shiotani, A El-Zimaity, HMT AF Graham, David Y. Shiotani, Akiko El-Zimaity, Hala M. T. TI Chromoendoscopy points the way to understanding recovery of gastric function after Helicobacter pylori eradication SO GASTROINTESTINAL ENDOSCOPY LA English DT Editorial Material ID ATROPHIC BODY GASTRITIS; CONGO RED TEST; DUODENAL-ULCER SUBJECTS; ACID-SECRETION; INTESTINAL METAPLASIA; FOLLOW-UP; FUNDAL GASTRITIS; MUCOSAL ATROPHY; SYDNEY SYSTEM; INFECTION C1 Baylor Coll Med, Dept Med, Michael E DeBakey Vet Affairs Med Ctr, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Michael E DeBakey Vet Affairs Med Ctr, Dept Mol Virol, Houston, TX 77030 USA. Baylor Coll Med, Dept Med, Michael E DeBakey Vet Affairs Med Ctr, Dept Microbiol, Houston, TX 77030 USA. Wakayama Univ, Hlth Adm Ctr, Wakayama, Japan. Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. RP Graham, DY (reprint author), Baylor Coll Med, Dept Med, Michael E DeBakey Vet Affairs Med Ctr, Dept Med, Houston, TX 77030 USA. FU NIDDK NIH HHS [DK56338] NR 58 TC 9 Z9 9 U1 0 U2 0 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 NOV PY 2006 VL 64 IS 5 BP 686 EP 690 DI 10.1016/j.gie.2006.03.013 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 099YR UT WOS:000241634300004 PM 17055857 ER PT J AU Brugge, WR AF Brugge, William R. TI The mistletoe and cyst-fluid analysis: a sticky insight SO GASTROINTESTINAL ENDOSCOPY LA English DT Editorial Material ID DIFFERENTIAL-DIAGNOSIS; PANCREATIC CYSTS; FIBROSIS SPUTUM; NEOPLASMS; VISCOSITY; EXPRESSION; LESIONS; PSEUDOCYSTS C1 Massachusetts Gen Hosp, GI Endoscopy Unit, Boston, MA 02114 USA. RP Brugge, WR (reprint author), Massachusetts Gen Hosp, GI Endoscopy Unit, Boston, MA 02114 USA. NR 20 TC 4 Z9 4 U1 0 U2 1 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 NOV PY 2006 VL 64 IS 5 BP 703 EP 704 DI 10.1016/j.gie.2006.04.019 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 099YR UT WOS:000241634300007 PM 17055860 ER PT J AU Jensen, DM Machicado, GA Hirabayashi, K AF Jensen, Dennis M. Machicado, Gustavo A. Hirabayashi, Ken TI Randomized controlled study of 3 different types of hemoclips for hemostasis of bleeding canine acute gastric ulcers SO GASTROINTESTINAL ENDOSCOPY LA English DT Article ID ENDOSCOPIC HEMOCLIP; PEPTIC-ULCER; ETHANOL INJECTION; TRIAL; THERAPY; HEMORRHAGE; CLIP AB Background: Mechanical closure of bleeding vessels is clinically appealing, and several types of hemoclips are now marketed for endoscopic hemostasis of nonvariceal lesions. No comparative data have been reported on ease of clip placement, hemostasis efficacy, or clip retention rates on bleeding ulcers. Objective: To compare 3 different types of hemoclips for hemostasis of bleeding ulcers. Design: Randomized controlled study Subjects: Seven adult dogs with prehepatic portal hypertension were heparinized, and acute gastric ulcers were made with jumbo biopsy forceps. Animals had oral proton pump inhibitors daily and weekly endoscopies to quantitate clip retention and ulcer healing. Interventions: Bleeding ulcers were randomized in pairs (2 for each treatment/dog) to endoscopic hemoclip treatment or control. Main Outcome Measurements: Initial times and success of deployment, hemostasis efficacy, clip retention rates, and ulcer healing during endoscopic follow-ups. Results: There was no difference in initial hemostasis rates of hemoclips, and no major complications occurred. Ulcer healing times were faster (Resolution Clip [RC] or TriClip [TC]) or similar (QuickClip2 [QC]) to controls. Clip retention at I week was significantly less with TC and, at 3 to 7 weeks, was significantly higher with RC. Conclusions: (1) For the 3 hemoclip devices, initial hemostasis rates were 100%, but all devices required similar learning time to place clips successfully (2) Short-term retention rates of TC were significantly less than QC or RC. (3) Long-term clip retention was significantly higher with RC. (4) All 3 hemoclips were safe, and none interfered with ulcer healing. C1 Univ Calif Los Angeles, CURE Digest Dis Res Ctr, David Geffen Sch Med, CURE Hemostasis Res Grp, Los Angeles, CA 90073 USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Jensen, DM (reprint author), Univ Calif Los Angeles, CURE Digest Dis Res Ctr, David Geffen Sch Med, CURE Hemostasis Res Grp, Bldg 115,Rm 318,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. FU NIDDK NIH HHS [K24 DK02650] NR 20 TC 37 Z9 37 U1 0 U2 1 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 NOV PY 2006 VL 64 IS 5 BP 768 EP 773 DI 10.1016/j.gie.2006.06.031 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 099YR UT WOS:000241634300019 PM 17055872 ER PT J AU Cooper, MP Qu, LS Rohas, LM Lin, JD Yang, WL Erdjument-Bromage, H Tempst, P Spiegelman, BM AF Cooper, Marcus P. Qu, Lishu Rohas, Lindsay M. Lin, Jiandie Yang, Wenli Erdjument-Bromage, Hediye Tempst, Paul Spiegelman, Bruce M. TI Defects in energy homeostasis in Leigh syndrome French Canadian variant through PGC-1 alpha/LRP130 complex SO GENES & DEVELOPMENT LA English DT Article DE PGC-1 alpha; LRP130; LPRPRC; Leigh syndrome; gluconeogenesis ID FORKHEAD TRANSCRIPTION FACTOR; C-OXIDASE DEFICIENCY; THERMOGENIC COACTIVATOR PGC-1; PPAR-GAMMA COACTIVATOR-1; MITOCHONDRIAL BIOGENESIS; HEPATIC GLUCONEOGENESIS; MESSENGER-RNA; FACTOR FKHR; IN-VIVO; NUCLEAR AB Leigh syndrome French Canadian variant (LSFC) is an autosomal recessive neurodegenerative disorder due to mutation in the LRP130 (leucine-rich protein 130 kDa) gene. Unlike classic Leigh syndrome, the French Canadian variant spares the heart, skeletal muscle, and kidneys, but severely affects the liver. The precise role of LRP130 in cytochrome c oxidase deficiency and hepatic lactic acidosis that accompanies this disorder is unknown. We show here that LRP130 is a component of the PGC-1 alpha (peroxisome proliferator-activated receptor coactivator 1-alpha) transcriptional coactivator holocomplex and regulates expression of PEPCK ( phosphoenolpyruvate carboxykinase), G6P (glucose-6-phosphatase), and certain mitochondrial genes through PGC-1 alpha. Reduction of LRP130 in fasted mice via adenoviral RNA interference (RNAi) vector blocks the induction of PEPCK and G6P, and blunts hepatic glucose output. LRP130 is also necessary for PGC-1 alpha-dependent transcription of several mitochondrial genes in vivo. These data link LRP130 and PGC-1 alpha to defective hepatic energy homeostasis in LSFC, and reveal a novel regulatory mechanism of glucose homeostasis. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Univ Michigan, Dept Cell & Dev Biol, Ann Arbor, MI 48109 USA. Univ Michigan, Inst Life Sci, Ann Arbor, MI 48109 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Spiegelman, BM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. EM bruce_spiegelman@dfci.harvard.edu OI Tempst, Paul/0000-0002-6680-3987 FU NCI NIH HHS [P30 CA008748, P30 CA08748]; NIDDK NIH HHS [P30 DK040561, K08 DK071017, K08DK071017, P30 DK040561-11, R01 DK061562, R01DK61562] NR 44 TC 61 Z9 67 U1 0 U2 7 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD NOV 1 PY 2006 VL 20 IS 21 BP 2996 EP 3009 DI 10.1101/gad.1483906 PG 14 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 101VB UT WOS:000241767900010 PM 17050673 ER PT J AU Iwasaki, H Mizuno, S Arinobu, Y Ozawa, H Mori, Y Shigematsu, H Takatsu, K Tenen, DG Akashi, K AF Iwasaki, Hiromi Mizuno, Shin-ichi Arinobu, Yojiro Ozawa, Hidetoshi Mori, Yasuo Shigematsu, Hirokazu Takatsu, Kiyoshi Tenen, Daniel G. Akashi, Koichi TI The order of expression of transcription factors directs hierarchical specification of hematopoietic lineages SO GENES & DEVELOPMENT LA English DT Article DE hematopoiesis; hematopoietic progenitors; transcription factor ID COLONY-STIMULATING FACTOR; COMMON MYELOID PROGENITOR; MAST-CELLS; EOSINOPHIL LINEAGE; C/EBP-ALPHA; COMMITTED PROGENITORS; ERYTHROID-CELLS; FACTOR GATA-1; BONE-MARROW; PU.1 AB The mechanism of lineage specification in multipotent stem cells has not been fully understood. We recently isolated progenitors with the eosinophil, basophil, or mast cell lineage potential, all of which originate from granulocyte/ monocyte progenitors (GMPs). By using these prospectively purified progenitors, we show here that the expression timing of GATA-2 and CCAAT enhancer-binding protein alpha (C/EBP alpha) can differentially control their lineage commitment. The expression of GATA-2 instructed C/EBP alpha-expressing GMPs to commit exclusively into the eosinophil lineage, while it induced basophil and/or mast cell lineage commitment if C/EBP alpha was suppressed at the GMP stage. Furthermore, simply by switching the order of C/EBP alpha and GATA-2 transduction, even lymphoid-committed progenitors recaptured these developmental processes to be reprogrammed into each of these lineages. We propose that the order of expression of key transcription factors is critical for their interplay to selectively drive lineage specification programs, by which stem cells could generate multiple lineage cells in a hierarchical manner. C1 Kyushu Univ Hosp, Ctr Cellular & Mol Med, Fukuoka 8128582, Japan. Harvard Univ, Sch Med, Dept Canc Immunol & AIDS, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Tokyo, Div Immunol, Dept Microbiol & Immunol, Inst Med Sci, Tokyo 1088639, Japan. Harvard Univ, Sch Med, Harvard Inst Med, Boston, MA 02115 USA. RP Akashi, K (reprint author), Kyushu Univ Hosp, Ctr Cellular & Mol Med, Fukuoka 8128582, Japan. EM koichi_akashi@dfci.harvard.edu OI Tenen, Daniel/0000-0002-6423-3888 FU NCI NIH HHS [CA072009, P01 CA072009]; NHLBI NIH HHS [HL56745, R01 HL056745]; NIDDK NIH HHS [DK050654, DK061320, P01 DK050654, R01 DK061320] NR 53 TC 155 Z9 163 U1 1 U2 4 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD NOV 1 PY 2006 VL 20 IS 21 BP 3010 EP 3021 DI 10.1101/gad.1493506 PG 12 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 101VB UT WOS:000241767900011 PM 17079688 ER PT J AU Adams, DS Levin, M AF Adams, Dany S. Levin, Michael TI Inverse drug screens: A rapid and inexpensive method for implicating molecular targets SO GENESIS LA English DT Article DE screen; pharmacology; blockers; inhibitors ID LEFT-RIGHT ASYMMETRY; METABOTROPIC RECEPTOR ACTIVATION; INDUCIBLE GENE-EXPRESSION; CHEMICAL GENETICS; METABOLIC NETWORKS; EARLY STEP; FROG EMBRYOS; RNAI SCREEN; SEROTONIN; ZEBRAFISH AB Identification of gene products that function in some specific process of interest is a common goal in developmental biology. Although use of drug compounds to probe biological systems has a very long history in teratology and toxicology, systematic hierarchical drug screening has not been capitalized upon by the developmental biology community. This "chemical genetics" approach can greatly benefit the study of embryonic and regenerative systems, and we have formalized a strategy for using known pharmacological compounds to implicate specific molecular candidates in any chosen biological phenomenon. Taking advantage of a hierarchical structure that can be imposed on drug reagents in a number of fields such as ion transport, neurotransmitter function, metabolism, and cytoskeleton, any assay can be carried out as a binary search algorithm. This inverse drug screen methodology is much more efficient than exhaustive testing of large numbers of drugs, and reveals the identity of a manageable number of specific molecular candidates that can then be validated and targeted using more expensive and specific molecular reagents. Here, we describe the process of this loss-of-function screen and illustrate its use in uncovering novel bioelectrical and serotonergic mechanisms in embryonic patterning. This technique is an inexpensive and rapid complement to existing molecular screening strategies. Moreover, it is applicable to maternal proteins, and model species in which traditional genetic screens are not feasible, significantly extending the opportunities to identify key endogenous players in biological processes. C1 Harvard Univ, Sch Dent Med, Ctr Regenerat & Dev Biol, Forsyth Inst, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Dept Dev Biol, Boston, MA 02115 USA. RP Levin, M (reprint author), Harvard Univ, Sch Dent Med, Ctr Regenerat & Dev Biol, Forsyth Inst, 140 Fenway, Boston, MA 02115 USA. EM mlevin@forsyth.org FU NCI NIH HHS [CO6RR11244]; NIDCR NIH HHS [K22 DE016633, 5K22DE016633, K22 DE016633-02]; NIGMS NIH HHS [1-R01-GM-06227] NR 58 TC 36 Z9 36 U1 1 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1526-954X J9 GENESIS JI Genesis PD NOV PY 2006 VL 44 IS 11 BP 530 EP 540 DI 10.1002/dvg.20246 PG 11 WC Developmental Biology; Genetics & Heredity SC Developmental Biology; Genetics & Heredity GA 108LX UT WOS:000242242400004 PM 17078061 ER PT J AU Newburg, DS Meng, D Young, C Baker, A Tonkonogy, SL Sartor, RB Walker, WA Nanthakumar, NN AF Newburg, David S. Di Meng Young, Cheryl Baker, Amy Tonkonogy, Susan L. Sartor, R. Balfour Walker, W. Allan Nanthakumar, N. Nanda TI Bacterial symbionts induce a fut2-dependent fucosylated niche on colonic epithelium via a TLR-4 sentinel that activates ERK and JNK signaling SO GLYCOBIOLOGY LA English DT Meeting Abstract CT Meeting of the Society-for-Gylcobiology CY NOV 15-19, 2006 CL Universal City, CA SP Soc Gylcobiol C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. N Carolina State Univ, Raleigh, NC 27695 USA. Univ N Carolina, Chapel Hill, NC 27515 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2006 VL 16 IS 11 MA 76 BP 1118 EP 1118 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 092JR UT WOS:000241093300082 ER PT J AU Littell, RD Hallonquist, H Matulonis, U Seiden, MV Berkowitz, RS Duska, LR AF Littell, Ramey D. Hallonquist, Heidi Matulonis, Ursula Seiden, Michael V. Berkowitz, Ross S. Duska, Linda R. TI Negative laparoscopy is highly predictive of negative second-look laparotomy following chemotherapy for ovarian, tubal, and primary peritoneal carcinoma SO GYNECOLOGIC ONCOLOGY LA English DT Article DE ovarian cancer; second-look surgery; clinical trial; laparoscopy ID CANCER; COMPLICATIONS; SURVIVAL; SURGERY AB Objective. To determine the negative predictive value of second-look laparoscopy compared to laparotomy for assessment of pathologic complete response (CR) in patients with epithelial ovarian, tubal, and peritoneal carcinoma who achieved a clinical CR. Methods. Data were analyzed from patients who participated in two sequential phase II clinical trials following primary cytoreductive surgery. Both trials required surgical evaluation for pathologic CR in those patients who achieved clinical CR. Protocol specified that assessment begin with laparoscopy; if negative, conversion to laparotomy was required. Collection of peritoneal washings was performed laparoscopically. Results. One hundred thirty-six patients entered the 2 sequential clinical trials. Ninety-nine patients achieved clinical CR and 95 underwent second-look surgery (SLO). Seventy patients began SLO with laparoscopy and converted to planned laparotomy after biopsies were negative. Eighteen cases were positive based on laparoscopy with frozen section. Five additional patients had peritoneal washings and/or permanent pathology positive based on laparoscopic findings, yielding a positive SLO rate of 32.9%. Four of the 52 patients who underwent laparotomy (7.7%) were found to have persistent disease that was not detected on laparoscopic biopsy or washings and represent false-negative laparoscopy; all four patients had disease at peritoneal-based sites. The sensitivity and negative predictive value for intraoperative diagnosis of persistent disease by laparoscopy were 66.6% and 82.7%, respectively. The sensitivity and negative predictive value of laparoscopic peritoneal biopsies and washings compared to laparotomy, as determined by final pathology, were 85.2% and 91.5%, respectively. Conclusion. A negative second-look laparoscopy with negative peritoneal pathology and cytology is 91.5% predictive of negative laparotomy and is associated with a low complication rate even in the setting of prior extensive cytoreductive surgery. The small increase in sensitivity and negative predictive value afforded by laparotomy does not warrant the increased morbidity. (c) 2006 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Div Gynecol Oncol, Boston, MA 02114 USA. Dana Farber Canc Inst, Div Med Oncol, Boston, MA 02215 USA. Massachusetts Gen Hosp, Div Med Oncol, Boston, MA 02114 USA. Brigham & Womens Hosp, Div Gynecol Oncol, Boston, MA 02215 USA. RP Duska, LR (reprint author), Massachusetts Gen Hosp, Gillette Ctr Womens Canc, Yawkey 9,55 Fruit St, Boston, MA 02114 USA. EM lduska@partners.org OI Littell, Ramey/0000-0001-6096-6075 NR 21 TC 13 Z9 15 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 NOV PY 2006 VL 103 IS 2 BP 570 EP 574 DI 10.1016/j.ygyno.2006.04.011 PG 5 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 101SA UT WOS:000241759600034 PM 16769104 ER PT J AU Matulonis, UA Campos, S Krasner, CN Duska, LR Penson, RT Falke, R Roche, M Smith, LM Lee, H Seiden, MV AF Matulonis, U. A. Campos, S. Krasner, C. N. Duska, L. R. Penson, R. T. Falke, R. Roche, M. Smith, L. M. Lee, H. Seiden, M. V. CA Dana Farber Partners CancerCare Ha TI Three sequential chemotherapy doublets for the treatment of newly diagnosed advanced mullerian malignancies: The modified triple doublet regimen SO GYNECOLOGIC ONCOLOGY LA English DT Article DE ovarian cancer; topotecan; gemcitabine; adriamycin; paclitaxel; carboplatin; filgrastim ID GYNECOLOGIC-ONCOLOGY-GROUP; ADVANCED OVARIAN-CANCER; PHASE-II TRIAL; CARBOPLATIN; PACLITAXEL; TOPOTECAN; COMBINATION; DOXORUBICIN; CARCINOMA; CISPLATIN AB Objective. Previously, we reported the use of three sequential doublets (Triple Doublets) in the treatment of women with newly diagnosed and advanced stage mullerian malignancies. The surgically defined negative second look operation (SLO) rate to Triple Doublets was 38%. Modifications were made to this treatment regimen that were predicted to reduce toxicity and possibly increase efficacy. Methods. Open label two-cohort study. Patients with a new diagnosis of Stages II-IV mullerian malignancy were eligible. After cytoreductive surgery, patients were treated with three sequential doublets including 3 cycles of carboplatin and gemcitabine, and 3 cycles of carboplatin and paclitaxel, and 3 cycles of doxorubicin and topotecan. After therapy, all women were clinically staged and evaluated at SLO if clinical staging was negative for residual disease. Primary endpoints were toxicity and negative SLO rate with rates of 60% and 40% defined a priori in optimally cytoreduced (cohort 1) and suboptimally cytoreduced or Stage IV (cohort 2), respectively. Results. Eighty-five eligible patients were enrolled with a median age of 52 years. Forty-seven and thirty-eight women were in cohorts 1 and 2, respectively. 723 cycles of chemotherapy were delivered with no toxic deaths. Grades 3 and 4 toxicities included neutropenia in 75% of patients and thrombocytopenia in 65% of patients during at least one cycle of therapy. Fever and neutropenia were seen in 3.5% of patients. All Grades 3 and 4 non-hematologic toxicities were seen at a frequency of < 10%. Seventy women underwent SLO with a negative SLO rate of 53% with an additional 9% having microscopically positive procedures. Negative SLO rate was 74% in cohort 1 and 36% in cohort 2. Conclusions. Treatment with the modified triple doublet regimen is tolerable with an encouraging pathologic CR rate. (c) 2006 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Div Med Oncol, Boston, MA 02114 USA. Dana Farber Canc Inst, Div Med Oncol, Boston, MA 02115 USA. Harvard Vanguard Med Ctr, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Gynecol Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Biostat, Boston, MA 02115 USA. RP Seiden, MV (reprint author), Massachusetts Gen Hosp, Div Med Oncol, Cox 640,100 Blossom St, Boston, MA 02114 USA. EM mseiden@partners.org NR 15 TC 5 Z9 5 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 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD NOV PY 2006 VL 103 IS 2 BP 575 EP 580 DI 10.1016/j.ygyno.2006.04.017 PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 101SA UT WOS:000241759600035 PM 16806439 ER PT J AU Vaidya, AP Horowitz, NS Oliva, E Halpern, EF Duska, LR AF Vaidya, Ami P. Horowitz, Neil S. Oliva, Esther Halpern, Elkan F. Duska, Linda R. TI Uterine malignant mixed mullerian tumors should not be included in studies of endometrial carcinoma SO GYNECOLOGIC ONCOLOGY LA English DT Article DE endometrial; carcinosarcoma; malignant mixed mullerian tumors ID GYNECOLOGIC-ONCOLOGY-GROUP; PHASE-III TRIAL; PACLITAXEL; CHEMOTHERAPY; DOXORUBICIN; CANCER; RISK; CARCINOSARCOMAS; IRRADIATION; CARBOPLATIN AB Objective. Uterine mixed malignant mullerian tumors (MMMT) have traditionally been excluded from clinical trials of endometrial cancer because of a belief that they are more correctly included in the sarcoma category. Recently, investigators have suggested that uterine MMMTs are actually dedifferentiated epithelial tumors and should be treated as such. The current study was undertaken to compare outcomes, stage for stage, of uterine MMMT with poor prognosis endometrial adenocarcinomas. Methods. Cases of MMMT from 1996 to 2004 were identified from the Tumor Registry after IRB consent was obtained. Retrospective chart review was performed. Cases were matched by age, stage, performance status, and surgical procedure to controls consisting of grade 3 endometrioid, papillary serous, and clear cell endometrial carcinomas from the same time period. Overall survival was compared using the Log-Rank test. Results. 68 patients with MMMT were identified. 23 were excluded due to incomplete records. Patients with MMMT ranged in age from 51 to 95 years (mean 75.3 years). Approximately half of the patients (53%) had stage III or IV disease. Of the controls, 31 (69%) had grade 3 endometrioid, 11 (24%) papillary serous, and 3 (7%) clear cell carcinoma. Median overall survival for all patients with MMMT was significantly shorter than for controls, 18 months (range 0.5-72) versus 36 months (range 0.5-123) (P = 0.02). Patients with early stage disease (stage I or II) had shorter median survival than controls, 26 months (range 3-7) vs. 95 months (range 4-123) (P = 0.003). There was no difference in median survival when comparing advanced disease (stage III or IV) to matched controls, 15 months (range 0.5-70) vs. 19 months (range 0.5-100) (P = NS). Conclusions. Patients with uterine MMMT have a poorer prognosis than those patients with high grade epithelial tumors, especially for those with early stage disease. Given the discrepancy in survival, these patients should not be included in studies of endometrial carcinoma. Further investigations are necessary to identify factors to improve survival of these patients. (c) 2006 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Gillette Ctr Womens Canc, Div Gynecol Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Stat, Boston, MA 02114 USA. RP Duska, LR (reprint author), Massachusetts Gen Hosp, Gillette Ctr Womens Canc, Div Gynecol Oncol, 55 Fruit St, Boston, MA 02114 USA. EM lduska@partners.org NR 13 TC 32 Z9 37 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 NOV PY 2006 VL 103 IS 2 BP 684 EP 687 DI 10.1016/j.ygyno.2006.05.009 PG 4 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 101SA UT WOS:000241759600054 PM 16797683 ER PT J AU Raab, MS Breitkreutz, I Hundemer, M Benner, A Klaus, J Hegenbart, U Moehler, T Ho, AD Zeier, M Goldschmidt, H AF Raab, Marc S. Breitkreutz, Iris Hundemer, Michael Benner, Axel Klaus, Jens Hegenbart, Ute Moehler, Thomas ho, Antny D. Ho Zeier, Martin Goldschmidt, Hartmut TI The outcome of autologous stem cell transplantation in patients with plasma cell disorders and dialysis-dependent renal failure SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Article DE stem cell transplantation; multiple myeloma; renal failure; dialysis ID BONE-MARROW-TRANSPLANTATION; MULTIPLE-MYELOMA AB Patients with multiple myeloma and end-stage renal failure on dialysis are frequently not considered eligible for high-dose therapy (HDT) due to higher transplant-related mortality (TRM). Our aim was to evaluate the toxicity and survival of dialysis-dependent patients after HDT with melphalan (100 mg/m(2)) compared to those of patients without renal insufficiency (melphalan 200 mg/m(2)) in a matched pairs analysis of 34 patients. No significant differences were observed between hematologic toxicity, TRM or disease response. Dialysis patients showed comparable event-free and overall survival. They required significantly extended intravenous antibiotic treatment and longer hospitalization. Thus, melphalan 100 mg/m(2) is less toxic, yet equally efficient and improves the prognosis of this group of patients. C1 Univ Heidelberg, Dept Internal Med 5, Heidelberg, Germany. Natl Ctr Tumor Dis, Heidelberg, Germany. German Canc Res Ctr, Cent Unit Biostat, D-6900 Heidelberg, Germany. Univ Heidelberg, Dept Internal Med 1, Div Nephrol, Heidelberg, Germany. RP Raab, MS (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, 44 Binney St,Mayer Bldg 553, Boston, MA 02115 USA. EM Marc_Raab@dfci.harvard.edu NR 15 TC 19 Z9 20 U1 0 U2 1 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD NOV PY 2006 VL 91 IS 11 BP 1555 EP 1558 PG 4 WC Hematology SC Hematology GA 102GS UT WOS:000241799600024 PM 17082013 ER PT J AU Di Paola, J Aledort, L Britton, H Carcao, M Grabowski, E Hutter, J Journeycake, J Kempton, C Leissinger, C AF Di Paola, J. Aledort, L. Britton, H. Carcao, M. Grabowski, E. Hutter, J. Journeycake, J. Kempton, C. Leissinger, C. TI Application of current knowledge to the management of bleeding events during immune tolerance induction SO HAEMOPHILIA LA English DT Article DE bypassing agents; haemophilia; immune tolerance induction; inhibitor; prophylaxis ID RECOMBINANT FACTOR-VIIA; PROTHROMBIN COMPLEX CONCENTRATE; INHIBITOR BYPASS ACTIVITY; HIGH-RESPONDING INHIBITORS; FACTOR-IX INHIBITORS; HEMOPHILIA PATIENTS; RFVIIA-NOVOSEVEN; RANDOMIZED-TRIAL; ADVERSE EVENTS; SAFETY PROFILE AB The development of inhibitors to factor VIII is the most serious adverse event associated with the treatment of haemophilia A, predisposing patients to uncontrollable haemorrhage, disability and premature death. Eradication of inhibitors via immune tolerance induction (ITI) is effective in the majority of patients, but may require months to years to achieve success. In the interim, the treatment and prevention of acute bleeding episodes are primary foci of care. Regrettably, there is a paucity of information regarding management of bleeding episodes in inhibitor patients undergoing tolerization. Until specific data from ongoing clinical trials are available to provide more guidance in this patient group, it is reasonable and useful to rely on the broader base of medical literature pertaining to patients not being tolerized to deduce strategies for controlling acute and perioperative bleeding episodes in inhibitor patients during ITI. C1 Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA. Mt Sinai Sch Med, Dept Med, New York, NY USA. Univ Texas, Hlth Sci Ctr, Dept Pediat, San Antonio, TX 78284 USA. Hosp Sick Children, Dept Pediat Hematol, Toronto, ON M5G 1X8, Canada. Massachusetts Gen Hosp, Pediat Hematol Oncol Unit, Boston, MA 02114 USA. Univ Med Ctr, Dept Pediat Hematol Oncol, Tucson, AZ USA. Univ Texas, SW Med Ctr, Dept Pediat, Dallas, TX USA. Emory Univ, Dept Pediat Hematol Oncol & Bone Marrow Transplan, Atlanta, GA 30322 USA. Tulane Univ, Med Ctr, Louisiana Ctr Bleeding & Clotting, New Orleans, LA USA. RP Di Paola, J (reprint author), Univ Iowa, Dept Pediat, 200 Hawkins Dr, Iowa City, IA 52242 USA. EM jorge-dipaola@uiowa.edu NR 63 TC 6 Z9 6 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1351-8216 J9 HAEMOPHILIA JI Haemophilia PD NOV PY 2006 VL 12 IS 6 BP 591 EP 597 DI 10.1111/j.1365-2516.2006.01343.x PG 7 WC Hematology SC Hematology GA 101UW UT WOS:000241767300005 PM 17083508 ER PT J AU Huffman, JC Smith, FA Quinn, DK Fricchione, GL AF Huffman, Jeff C. Smith, Felicia A. Quinn, Davin K. Fricchione, Gregory L. TI Post-ML psychiatric syndromes: Six unanswered questions SO HARVARD REVIEW OF PSYCHIATRY LA English DT Review DE anxiety disorders; cardiovascular diseases; major depressive disorder; myocardial infarction ID CORONARY-HEART-DISEASE; ACUTE MYOCARDIAL-INFARCTION; SEROTONIN REUPTAKE INHIBITORS; PITUITARY-ADRENAL AXIS; C-REACTIVE PROTEIN; MAJOR DEPRESSION; RATE-VARIABILITY; CARDIOVASCULAR-DISEASE; VASCULAR DEPRESSION; ARTERY-DISEASE AB Depression, anxiety, and other psychological variables following acute myocardial infarction (NU) have been the subject of intense study over the last two decades. Through selective literature review and editorial commentary, we address six vital, unanswered questions concerning these psychological variables and their impact on coronary outcome. The picture that emerges is complex. Despite all that has been learned about the nature, consequences, and management of post-MI depression and related disorders, there remain many open issues. First, the prevalence, phenomenology, medical impact, and method of diagnosis of post-NU depression and other psychiatric syndromes remain unclear. In addition, at least four pathophysiologic mechanisms have been proposed to explain the link between depression and cardiac disease, but evidence of causation remains elusive. There have been increasingly well-designed treatment studies of post-MI depression, but the optimal agents and timing of treatment have yet to be defined. Finally, few recent studies of post-MI anxiety have been conducted. To make further progress, large, multicenter trials that use optimized screening tools, obtain data at several time points, consider multiple psychosocial variables, and correct carefully for medical/cardiac severity are required. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Huffman, JC (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 55 Fruit St Warren 1220C, Boston, MA 02114 USA. EM Jhuffman@partners.org NR 120 TC 7 Z9 8 U1 3 U2 4 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD NOV-DEC PY 2006 VL 14 IS 6 BP 305 EP 318 DI 10.1080/10673220601070013 PG 14 WC Psychiatry SC Psychiatry GA 122ZG UT WOS:000243265500003 PM 17162654 ER PT J AU Maalouf, FT Ziegler, RG Schlozman, S Prince, JB AF Maalouf, Fadi T. Ziegler, Robert G. Schlozman, Steven Prince, Jefferson B. TI Bipolar disorder in a preschooler: Long-term ramifications of an early diagnosis and treatment SO HARVARD REVIEW OF PSYCHIATRY LA English DT Article ID ADJUNCTIVE TOPIRAMATE; REFERRED CHILDREN; LIFE EVENTS; ADOLESCENTS; FAMILY; MANIA; PHENOTYPE; SYMPTOMS; ADHD; ARIPIPRAZOLE C1 Harvard Univ, Sch Med, Dept Psychiat, Boston, MA USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA USA. Cambridge Hlth Alliance, Cambridge, MA USA. RP Maalouf, FT (reprint author), Harvard Univ, Sch Med, Dept Psychiat, Boston, MA USA. NR 54 TC 1 Z9 1 U1 1 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1067-3229 J9 HARVARD REV PSYCHIAT JI Harv. Rev. Psychiatr. PD NOV-DEC PY 2006 VL 14 IS 6 BP 319 EP 329 DI 10.1080/10673220601082851 PG 11 WC Psychiatry SC Psychiatry GA 122ZG UT WOS:000243265500004 PM 17162655 ER PT J AU Jha, AK Ferris, TG Donelan, K DesRoches, C Shields, A Rosenbaum, S Blumenthal, D AF Jha, Ashish K. Ferris, Timothy G. Donelan, Karen DesRoches, Catherine Shields, Alexandra Rosenbaum, Sara Blumenthal, David TI How common are electronic health records in the United States? A summary of the evidence SO HEALTH AFFAIRS LA English DT Article ID PHYSICIAN ORDER ENTRY; INFORMATION-TECHNOLOGY; ADOPTION; SYSTEMS; QUALITY; CARE AB Electronic health records (EHRs) are promising tools to improve quality and efficiency in health care, but data on their adoption rate are limited. We identified surveys on EHR adoption and assessed their quality. Although surveys returned widely different estimates of EHR use, when available information is limited to studies of high or medium quality, national estimates are possible: Through 2005, approximately 23.9 percent of physicians used EHRs in the ambulatory setting, while 5 percent of hospitals used computerized physician order entry. Large gaps in knowledge, including information about EHR use among safety-net providers, pose critical challenges for the development of policies aimed at speeding adoption. C1 Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA USA. George Washington Univ, Dept Hlth Policy, Washington, DC USA. RP Jha, AK (reprint author), Harvard Univ, Sch Publ Hlth, 665 Huntington Ave, Boston, MA 02115 USA. EM ajha@hsph.harvard.edu NR 19 TC 119 Z9 119 U1 1 U2 6 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD NOV-DEC PY 2006 VL 25 IS 6 BP W496 EP W507 DI 10.1377/hlthaff.25.w496 PG 12 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 105MD UT WOS:000242033300053 PM 17035341 ER PT J AU Huffman, JC Smith, FA Blais, MA Beiser, ME Januzzi, JL Fricchione, GL AF Huffman, J. C. Smith, F. A. Blais, M. A. Beiser, M. E. Januzzi, J. L. Fricchione, G. L. TI Rapid screening for major depression in post-myocardial infarction patients: an investigation using Beck Depression Inventory II items SO HEART LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; CORONARY-HEART-DISEASE; MEDICAL INPATIENTS; PRIMARY-CARE; TASK-FORCE; MORTALITY; HEALTH; PREVALENCE; MORBIDITY; SOCIETY AB Objective: To determine the ability of three questions from the Beck Depression Inventory II (BDI-II) to detect major depressive disorder (MDD) in a cohort of patients hospitalised for acute myocardial infarction (MI). Design: Prospective observational study. Setting: Coronary care unit and cardiac step-down unit of an urban academic medical centre. Patients: 131 post-MI patients within 72 h of symptom onset. Interventions: Patients were administered the BDI-II and participated in a structured diagnostic interview for MDD. Three individual BDI-II items ( regarding sadness, loss of interest and loss of pleasure) were examined individually and in two-question combinations to determine their ability to screen for MDD. Main outcome measures: Sensitivity, specificity, negative and positive predictive values and proportion of patients with MDD correctly identified. Results: The individual items and two-question combinations had good sensitivity (76- 94%), specificity (70 - 88%) and negative predictive values ( 97 - 99%). Item 1 ( sadness) performed the best of the individual items (48% with a positive response to the item had MDD; 3% with a negative response had MDD; over 80% of patients with MDD were correctly identified). A combination of questions about sadness and loss of interest performed best among the two-question combinations (37% with positive response had MDD v 1% with a negative response; 94% of patients with MDD were identified). Conclusions: One to two questions regarding sadness and loss of interest serve as simple and effective screening tools for post-MI depression. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Cardiol, Boston, MA 02114 USA. Columbia Univ, Sch Nursing, New York, NY USA. RP Huffman, JC (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 55 Fruit St,Warren 1220 C, Boston, MA 02114 USA. EM jhuffman@partners.org NR 29 TC 17 Z9 19 U1 1 U2 2 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1355-6037 J9 HEART JI Heart PD NOV PY 2006 VL 92 IS 11 BP 1656 EP 1660 DI 10.1136/hrt.2005.087213 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 095QJ UT WOS:000241322400024 PM 16644855 ER PT J AU Singh, JP Fan, D Heist, EK Alabiad, CR Taub, C Reddy, V Mansour, M Picard, MH Ruskin, JN Mela, T AF Singh, Jagmeet P. Fan, Dah Heist, E. Kevin Alabiad, Chrisfouad R. Taub, Cynthia Reddy, Vivek Mansour, Moussa Picard, MichaeL H. Ruskin, Jeremy N. Mela, Theofanie TI Left ventricular lead electrical delay predicts response to cardiac resynchronization therapy SO HEART RHYTHM LA English DT Article DE cardiac resynchronization therapy; heart failure; electrograms; hemodynamics ID CONGESTIVE-HEART-FAILURE; BUNDLE-BRANCH BLOCK; SYSTOLIC FUNCTION; STIMULATION SITE; CARDIOMYOPATHY AB BACKGROUND Intracardiac electrograms can be used to guide Left ventricular (LV) Lead placement during implantation of cardiac resynchronization therapy (CRT) devices. Although attempts often are made to ensure that the LV Lead is positioned at a site of maximal electrical delay, information on whether this is useful in predicting the acute hemodynamic response and Long-term clinical outcome to CRT is limited. OBJECTIVES The purpose of this study was to assess the ability of intracardiac (electrogram) measurements made during LV lead placement in patients undergoing CRT for predicting acute hemodynamic response and Long-term clinical outcome to CRT. METHODS Seventy-one subjects with standard indications for CRT underwent electrogram measurements and echocardiograms performed in the acute phase of this study. The LV lead electrical delay was measured intraoperatively from the onset of the surface ECG QRS complex to the onset of the sensed electrogram on the LV lead, as a percentage of the baseline QRS interval. Echocardiographic assessment of the hemodynamic response to CRT was measured as an intra-individual percentage change in dP/dt over baseline (Delta dP/dt, derived from the mitral regurgitation Doppler profile) with CRT on and off. dP/dt was measurable in 48 subjects, and acute responders to CRT were defined as those with Delta dP/dt >= 25%. Long-term response was measured as a combined endpoint of hospitalization for heart failure and/or all cause mortality at 12 months. Time to the primary endpoint was estimated by the Kaplan-Meier method, with comparisons made using the log rank test. RESULTS LV Lead electrical delay correlated weakly with Delta dP/dt of the combined group (n = 48, r = 0.311, P = .029) but was strongly correlated with Delta dP/dt in the nonischemic subgroup (n = 20, r = 0.48, P = .027). LV Lead electrical delay (%) was significantly longer in acute responders (69.6 +/- 23.9 vs 31.95 +/- 11.57, P = .002) among patients with nonischemic cardiomyopathy. A reduced LV lead electrical delay (<50% of the QRS duration) was associated with worse clinical outcome within the entire cohort (hazard ratio: 2.7, 95% confidence interval: 1.17-6.68, P = .032) as well as when stratified into ischemic and nonischemic subgroups. CONCLUSION Measuring LV lead electrical delay is useful during CRT device implantation because it may help predict hemodynamic response and long-term clinical outcome. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. RP Singh, JP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Arrhythmia Serv, GRB 109,55 Fruit St, Boston, MA 02114 USA. EM jsingh@partners.org OI Picard, Michael/0000-0002-9264-3243 NR 25 TC 104 Z9 107 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1547-5271 J9 HEART RHYTHM JI Heart Rhythm PD NOV PY 2006 VL 3 IS 11 BP 1285 EP 1292 DI 10.1016/j.hrthm.2006.07.034 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 104KU UT WOS:000241958100003 PM 17074633 ER PT J AU Heist, EK Refaat, M Danik, SB Homvang, G Ruskin, JN Mansour, M AF Heist, E. Kevin Refaat, Marwan Danik, Stephan B. Homvang, Godtfred Ruskin, Jeremy N. Mansour, Moussa TI Analysis of the left atrial appendage by magnetic resonance angiography in patients with atrial fibrillation SO HEART RHYTHM LA English DT Article DE atrial fibrillation; cardiac anatomy; left atrial appendage; magnetic resonance imaging; occlusion device ID CONTRAST-ENHANCED MRI; TRANSESOPHAGEAL ECHOCARDIOGRAPHY; TRANSCATHETER OCCLUSION; THROMBUS; RISK; EXPERIENCE; ABLATION; PLAATO; STROKE AB BACKGROUND Recent interest has focused on the left atrial appendage (LAA) in the setting of atrial fibrillation as a potential source of thromboembolism and stroke, which may be amenable to permanent occlusion by a variety of investigational catheter-delivered devices. Precise anatomic characterization of the LAA is necessary to determine the suitability of a patient for device placement and for device selection and sizing. OBJECTIVES The purpose of this study was to perform detailed three-dimensional characterization of LAA size and geometry by magnetic resonance angiography. METHODS Fifty patients with chronic atrial fibrillation undergoing cardiac magnetic resonance angiography in preparation for catheter ablation of atrial fibrillation were analyzed for LAA volume, neck size, depth, and overall geometry. RESULTS The average LAA volume was 17.3 +/- 6.7 mL, with a depth of 26.6 +/- 4.9 mm and a "neck" diameter of 20.0 +/- 5.3 mm X 14.1 +/- 4.7 mm. The average number of LAA lobes was 1.4 +/- 0.7 (range 1-4). Substantial interpatient variability was present in the relative dimensions and morphology of the LAA. There was a significant correlation between left atrial size and LAA neck dimensions. CONCLUSION There is significant heterogeneity in LAA size and dimensions among patients with atrial fibrillation. Device occlusion of the LAA may require devices that are available in multiple sizes/shapes or that can adapt to this heterogeneity. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA 02114 USA. RP Mansour, M (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Arrhythmia Serv, Gray 109,55 Fruit St, Boston, MA 02114 USA. EM mmansour@partners.org NR 14 TC 55 Z9 56 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1547-5271 J9 HEART RHYTHM JI Heart Rhythm PD NOV PY 2006 VL 3 IS 11 BP 1313 EP 1318 DI 10.1016/j.hrthm.2006.07.022 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 104KU UT WOS:000241958100007 PM 17074637 ER PT J AU Mansour, M Rasche, V Picard, MH Ruskin, JN AF Mansour, Moussa Rasche, Volker Picard, Michael H. Ruskin, Jeremy N. TI Integration of three-dimensional coronary venous angiography with three-dimensional echocardiography for biventricular device implantation SO HEART RHYTHM LA English DT Editorial Material C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac Arrhythmia Unit, Boston, MA 02114 USA. Philips Med Syst, Andover, MA USA. Univ Ulm, Dept Internal Med, D-7900 Ulm, Germany. RP Mansour, M (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac Arrhythmia Unit, Gray 109,55 Fruit St, Boston, MA 02114 USA. EM mmansour@partners.org RI Rasche, Volker/P-6523-2016; OI Rasche, Volker/0000-0001-8844-3583; Picard, Michael/0000-0002-9264-3243 NR 2 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1547-5271 J9 HEART RHYTHM JI Heart Rhythm PD NOV PY 2006 VL 3 IS 11 BP 1391 EP 1392 DI 10.1016/j.hrthm.2006.04.027 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 104KU UT WOS:000241958100023 PM 17074653 ER PT J AU Peters, MG Andersen, J Lynch, P Liu, T Alston-Smith, B Brosgart, CL Jacobson, JM Johnson, VA Poflard, RB Rooney, JF Sherman, KE Swindells, S Polsky, B AF Peters, Marion G. Andersen, Janet Lynch, Patrick Liu, Tun Alston-Smith, Beverly Brosgart, Carol L. Jacobson, Jeffrey M. Johnson, Victoria A. Poflard, Richard B. Rooney, James F. Sherman, Kenneth E. Swindells, Susan Polsky, Bruce CA ACTG Protocol A5127 Team TI Randomized controlled study of tenofovir and adefovir in chronic hepatitis B virus and HIV infection: ACTG A5127 SO HEPATOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY; DISOPROXIL FUMARATE; IN-VITRO; LAMIVUDINE; DIPIVOXIL; ANTIGEN; RECOMMENDATIONS; INDIVIDUALS; COMBINATION; PREVALENCE AB Chronic hepatitis B virus (HBV) infection is an important cause of morbidity and mortality in subjects coinfected with HIV. Tenofovir disoproxil fumarate (TDF) and adefovir dipivoxil (ADV) are licensed for the treatment of HIV-1 and HBV infection, respectively, but both have in vivo and in vitro activity against HBV. This study evaluated the anti-HBV activity of TDF compared to ADV in HIV/HBV-coinfected subjects. ACTG A5127 was a prospective randomized, double-blind, placebo-controlled trial of daily 10 mg of ADV versus 300 mg of TDF in subjects with HBV and HIV coinfection on stable ART, with serum HBV DNA >= 100,000 copies/mL, and plasma HIV-1 RNA:5 10,000 copies/mL. This study closed early based on results of a prespecified interim review, as the primary noninferiority end point had been met without safety issues. Fifty-two subjects were randomized. At baseline, 73% of subjects had a plasma HIV-1 RNA < 50 copies/mL, 86% were HBeAg positive, 94% were 3TC resistant, median serum ALT was 52 IU/L, and 98% had compensated liver disease. The mean time-weighted average change in serum HBV DNA from baseline to week 48 (DAVG(48)) was -4.44 log(10) copies/mL for TDF and -3.21 log(10) copies/mL for ADV. There was no difference in toxicity between the 2 treatment arms, with 11 subjects (5 ADV and 6 TDF) experiencing elevations of serum ALT on treatment. In conclusion, over 48 weeks, treatment with either ADV or TDF resulted in clinically important suppression of serum HBV DNA. Both drugs arc safe and efficacious for patients coinfected with HBV and HIV. C1 Univ Calif San Francisco, Div Gastroenterol, San Francisco, CA 94143 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Northwestern Univ, Sch Med, Chicago, IL USA. NIAID, NIH, AIDS Clin Trials Grp, Bethesda, MD USA. Gilead Sci Inc, Foster City, CA USA. Beth Israel Med Ctr, New York, NY 10003 USA. Albert Einstein Coll Med, New York, NY USA. Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. Univ Alabama, Birmingham Sch Med, Birmingham, AL USA. Univ Calif Davis, Med Ctr, Sacramento, CA 95817 USA. Univ Cincinnati, Coll Med, Cincinnati, OH USA. Univ Nebraska, Ctr Med, Omaha, NE 68198 USA. St Lukes Roosevelt Hosp, Div Infect Dis, New York, NY USA. Columbia Univ, Coll Phys & Surg, New York, NY USA. RP Peters, MG (reprint author), Univ Calif San Francisco, Div Gastroenterol, 513 Parnassus Ave,Room S-357, San Francisco, CA 94143 USA. EM marion.perers@ucsf.edu FU NCRR NIH HHS [M01-RR00096, RR-00052, RR00046, RR00047, RR00051]; NIAID NIH HHS [AI25915, 3U01AI38858-09S1, AI-27668, AI25868, AI32770, AI32782, AI38855, AI46370, AI46386, AI50410, P30 AI027767, P30 AI27767, U01 AI038855, U01 AI038858, U01 AI069502, U01AI38858]; NIDDK NIH HHS [P30 DK 26743, P30 DK026743]; PHS HHS [5 UO1 A1027665-18] NR 25 TC 111 Z9 123 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD NOV PY 2006 VL 44 IS 5 BP 1110 EP 1116 DI 10.1002/hep.21388 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 099IH UT WOS:000241586400006 PM 17058225 ER PT J AU Goldstein, JM AF Goldstein, Jill M. TI Sex, hormones and affective arousal circuitry dysfunction in schizophrenia SO HORMONES AND BEHAVIOR LA English DT Review DE schizophrenia; HPA and HPG axes; emotion; affective brain circuitry; sex differences ID FUNCTIONAL MAGNETIC-RESONANCE; ESTROGEN-RECEPTOR-ALPHA; PITUITARY-ADRENAL AXIS; CORTICOTROPIN-RELEASING-FACTOR; MESSENGER-RIBONUCLEIC-ACID; REPRODUCTIVE ENDOCRINE DISORDERS; POSITRON-EMISSION-TOMOGRAPHY; DIFFERENTIAL NEURAL RESPONSE; GONADAL-STEROID HORMONES; TEMPORAL-LOBE ORIGIN AB Women with schizophrenia express affective disturbances disproportionately more than men. Brain regions implicated in the affective arousal circuitry also regulate the hypothalamic-pituitary-adrenal and -gonadal systems, which are dysfunctional in schizophrenia. This review will argue that understanding the etiology of affective arousal deficits in schizophrenia is intimately connected with characterizing the role of neuroendocrine dysfunction and sex effects in schizophrenia. Further, the etiology of these neuroendocrine deficits begins during fetal development, during a period of time that coincides with the sexual differentiation of the brain and the vulnerability for schizophrenia. Studying the links between deficits in neuroendocrine systems and the affective arousal system in schizophrenia will provide clues to understanding the development of sex differences in schizophrenia and thereby its etiology. (c) 2006 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med, Dept Psychiat, Brigham & Womens Hosp,Dept Psychiat, Boston, MA 02120 USA. Connors Ctr Womens Hlth & Gender Biol, Div Womens Hlth, Dept Med, Boston, MA 02120 USA. Beth Israel Deaconess Hosp, Dept Psychiat, Publ Psychiat Div, Massachusetts Mental Hlth Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Goldstein, JM (reprint author), Brigham & Womens Hosp, Div Womens Hlth, 1 Brigham Circle,1620 Tremont St 3rd Floor, Boston, MA 02120 USA. EM jill_goldstein@hms.harvard.edu FU NIMH NIH HHS [R01 MH56956] NR 225 TC 46 Z9 48 U1 11 U2 15 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0018-506X J9 HORM BEHAV JI Horm. Behav. PD NOV PY 2006 VL 50 IS 4 BP 612 EP 622 DI 10.1016/j.yhbeh.2006.06.029 PG 11 WC Behavioral Sciences; Endocrinology & Metabolism SC Behavioral Sciences; Endocrinology & Metabolism GA 089GV UT WOS:000240869500014 PM 16876167 ER PT J AU Zuniga, J Romero, V Azocar, J Stern, JNH Clavijo, O Almeciga, I Encinales, L Avendano, A Fridkis-Hareli, M Pandey, JP Yunis, EJ AF Zuniga, Joaquin Romero, Viviana Azocar, Jose Stern, Joel N. H. Clavijo, Olga Almeciga, Ingrid Encinales, Liliana Avendano, Angel Fridkis-Hareli, Masha Pandey, Janardan P. Yunis, Edmond J. TI Interaction of KIR genes and G1M immunoglobulin allotypes confer susceptibility to type 2 diabetes in Puerto Rican Americans SO HUMAN IMMUNOLOGY LA English DT Article DE KIR; GM allotype; type 2 diabetes; epistasis; genetic susceptibility ID IMPAIRED GLUCOSE-TOLERANCE; NATURAL-KILLER-CELLS; C VIRUS-INFECTION; TNF-ALPHA; POPULATION STRATIFICATION; GENOMIC LEVEL; HLA ANTIGENS; INSULIN; MELLITUS; POLYMORPHISMS AB The susceptibility to type 2 diabetes (T2D) involves genetic factors. We studied the distribution of KIR and MHC class I ligands phenotype and genotype frequencies, as well as immunoglobulin KM and GM allotype frequencies in a group of patients (N = 95) with T2D and ethnically matched healthy controls (N = 74) with Puerto Rican ethnic background. We found a slight increase of the 2DL3/2DL3 homozygous genotype in T2D. Moreover, the association between 2DL3/2DL3 genotype was significant in the presence of 2DS4 (pC = 0.01). Also, we observed an epistatic effect of the interaction of 2DL3/2DL3, 2DS4 with allele z of G1M in T2D (PC = 0.004, OR = 3.60, 95% CI, 1.62-8.10). This genetic interaction between KIR and G1M allotypes, associated with T2D, was also significant by multiple logistic regression analysis (p < 0.0001, OR = 4.90, 95% CI, 2.12-11.3). We did not detect population stratification using unlinked short tandem repeat (STR) markers, demonstrating that the patients and controls were ethnically matched. Hence, we have demonstrated in this study an epistatic interaction between KIR genes and the G1M allotype that influences the susceptibility to T2D in Puerto Rican Americans. Our findings are important for understanding the autoimmune or innate immune inflammatory-mediated mechanisms involved in the pathogenesis of T2D. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Inst Nac Enfermedades Resp, Mexico City, DF, Mexico. Northgate Med Ctr, Springfield, MA USA. Med Univ S Carolina, Dept Microbiol & Immunol, Charleston, SC 29425 USA. RP Yunis, EJ (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, 44 Binney St, Boston, MA 02115 USA. EM edmond_yunis@dfci.harvard.edu OI Stern, Joel N.H./0000-0002-1259-2256 FU NHLBI NIH HHS [HL29583, HL59838]; NIAID NIH HHS [AI49213] NR 45 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0198-8859 J9 HUM IMMUNOL JI Hum. Immunol. PD NOV PY 2006 VL 67 IS 11 BP 907 EP 914 DI 10.1016/j.humimm.2006.08.297 PG 8 WC Immunology SC Immunology GA 116XR UT WOS:000242837600006 PM 17145370 ER PT J AU Macklin, EA Wayne, PM Kalish, LA Valaskatgis, P Thompson, J Pian-Smith, MCM Zhang, QH Stevens, S Goertz, C Prineas, RJ Buczynski, B Zusman, RM AF Macklin, Eric A. Wayne, Peter M. Kalish, Leslie A. Valaskatgis, Peter Thompson, James Pian-Smith, May C. M. Zhang, Qunhao Stevens, Stephanie Goertz, Christine Prineas, Ronald J. Buczynski, Beverly Zusman, Randall M. TI Stop Hypertension with the Acupuncture Research Program (SHARP) - Results of a randomized, controlled clinical trial SO HYPERTENSION LA English DT Article DE acupuncture; blood pressure; hypertension; randomized clinical trial; traditional Chinese medicine ID ALTERNATIVE MEDICINE; BLOOD-PRESSURE; PAIN; ELECTROACUPUNCTURE; COMPLEMENTARY; STIMULATION; RESPONSES; NEURONS; STRESS; HUMANS AB Case studies and small trials suggest that acupuncture may effectively treat hypertension, but no large randomized trials have been reported. The Stop Hypertension with the Acupuncture Research Program pilot trial enrolled 192 participants with untreated blood pressure ( BP) in the range of 140/90 to 179/109 mm Hg. The design of the trial combined rigorous methodology and adherence to principles of traditional Chinese medicine. Participants were weaned off antihypertensives before enrollment and were then randomly assigned to 3 treatments: individualized traditional Chinese acupuncture, standardized acupuncture at preselected points, or invasive sham acupuncture. Participants received <= 12 acupuncture treatments over 6 to 8 weeks. During the first 10 weeks after random assignment, BP was monitored every 14 days, and antihypertensives were prescribed if BP exceeded 180/110 mm Hg. The mean BP decrease from baseline to 10 weeks, the primary end point, did not differ significantly between participants randomly assigned to active ( individualized and standardized) versus sham acupuncture (systolic BP: -3.56 versus -3.84 mm Hg, respectively; 95% CI for the difference: -4.0 to 4.6 mm Hg; P = 0.90; diastolic BP: -4.32 versus -2.81 mm Hg, 95% CI for the difference: -3.6 to 0.6 mm Hg; P = 0.16). Categorizing participants by age, race, gender, baseline BP, history of antihypertensive use, obesity, or primary traditional Chinese medicine diagnosis did not reveal any subgroups for which the benefits of active acupuncture differed significantly from sham acupuncture. Active acupuncture provided no greater benefit than invasive sham acupuncture in reducing systolic or diastolic BP. C1 New England Inst Inc, Watertown, MA 02472 USA. New England Sch Acupuncture, Watertown, MA USA. Childrens Hosp Boston, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Boston, MA USA. Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. Samueli Inst, Alexandria, VA USA. RP Macklin, EA (reprint author), New England Inst Inc, 9 Galen St, Watertown, MA 02472 USA. EM EMacklin@NERIScience.com RI Macklin, Eric/E-2955-2013; OI Macklin, Eric/0000-0003-1618-3502; Goertz, Christine/0000-0002-4700-3669 FU NCCIH NIH HHS [U01 AT00210] NR 51 TC 76 Z9 90 U1 1 U2 18 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD NOV PY 2006 VL 48 IS 5 BP 838 EP 845 DI 10.1161/01.HYP.0000241090.28070.4c PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 127PE UT WOS:000243598000016 PM 17015784 ER PT J AU Merfeld, DM Gong, WS Morrissey, J Saginaw, M Haburcakova, C Lewis, RF AF Merfeld, Daniel M. Gong, Wangsong Morrissey, Jennifer Saginaw, Michael Haburcakova, Csilla Lewis, Richard F. TI Acclimation to chronic constant-rate peripheral stimulation provided by a vestibular prosthesis SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING LA English DT Article DE adaptation; guinea pig; neural prosthesis; vestibular implant; vestibulo-ocular reflex; VOR ID CONTEXT-SPECIFIC ADAPTATION; EXTRACELLULAR ELECTRICAL-STIMULATION; INNERVATING SEMICIRCULAR CANALS; LONG-TERM POTENTIATION; VESTIBULOOCULAR REFLEX; GUINEA-PIG; GALVANIC STIMULATION; COCHLEAR IMPLANTS; FOCAL ELECTRODES; ADAPTIVE-CHANGES AB We are developing two types of vestibular prosthetics that electrically stimulate afferent neurons. One type replaces absent sensory function by providing stimulation that modulates above and below a baseline established with the head stationary. The other type provides constant stimulation and is turned on only when necessary, for example, to override unnatural variations like those experienced by patients suffering from Menire's syndrome; this prosthesis does not provide motion information. Both prostheses require neural plasticity, which we investigated by providing chronic constant-rate stimulation to semicircular canal neurons in three guinea pigs. The stimulation was alternately switched on or off for eight consecutive weeks before being switched daily. A brisk horizontal nystagmus was measured when the stimulation was first turned on and then dissipated over the course of a day. The nystagmus demonstrated an after-effect in the opposite direction when the stimulation was turned off. The nystagmus that we measured after just a few (2 to 5) off-to-on transitions returned to baseline more rapidly than when first turned on. In fact, after many such off-to-on or on-to-off transitions, little nystagmus was evoked by turning the stimulation on or off. These findings show that the brain acclimates to constant-rate stimulation. C1 Massachusetts Eye & Ear Infirm, Jenks Vestibular Physiol Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. RP Merfeld, DM (reprint author), Massachusetts Eye & Ear Infirm, Jenks Vestibular Physiol Lab, Room 421,243 Charles St, Boston, MA 02114 USA. EM dan_merfeld@meei.harvard.edu FU NIDCD NIH HHS [R01 DC03066] NR 54 TC 55 Z9 57 U1 0 U2 3 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0018-9294 J9 IEEE T BIO-MED ENG JI IEEE Trans. Biomed. Eng. PD NOV PY 2006 VL 53 IS 11 BP 2362 EP 2372 DI 10.1109/TBME.2006.883645 PG 11 WC Engineering, Biomedical SC Engineering GA 098QC UT WOS:000241536900027 PM 17073343 ER PT J AU Iwasaki, H Akashi, K AF Iwasaki, Hiromi Akashi, Koichi TI Thymus exclusivity: All the right conditions for T cells SO IMMUNITY LA English DT Editorial Material ID MOUSE BONE-MARROW; PROGENITORS; EXPRESSION; SPECIFICATION; COMMITMENT; LINEAGE; PU.1 C1 Kyushu Univ Hosp, Ctr Cellular & Mol Med, Fukuoka 8128582, Japan. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Iwasaki, H (reprint author), Kyushu Univ Hosp, Ctr Cellular & Mol Med, Fukuoka 8128582, Japan. NR 10 TC 2 Z9 2 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD NOV PY 2006 VL 25 IS 5 BP 697 EP 700 DI 10.1016/j.immuni.2006.10.005 PG 4 WC Immunology SC Immunology GA 105WN UT WOS:000242063100004 PM 17098201 ER PT J AU Davis, AE AF Davis, Alvin E., III TI Mechanism of angioedema in first complement component inhibitor deficiency SO IMMUNOLOGY AND ALLERGY CLINICS OF NORTH AMERICA LA English DT Review ID HEREDITARY ANGIONEUROTIC-EDEMA; MOLECULAR-WEIGHT KININOGEN; TISSUE-PLASMINOGEN-ACTIVATOR; PLASMA KALLIKREIN/KININ SYSTEM; ANTIBODY IMMUNOSORBENT-ASSAY; N-LINKED GLYCOSYLATION; C1 INHIBITOR; FACTOR-XII; HAGEMAN-FACTOR; VASCULAR-PERMEABILITY AB Since shortly after the discovery that hereditary angioedema resulted from deficiency of first complement component (Cl) inhibitor, the characterization of the mediator of angioedema has been a major goal. However, because C1 inhibitor regulates activation of both the contact and complement systems, identification of the mediator was not immediately accomplished. For a number of years, some studies appeared to indicate involvement of one system, whereas other studies suggested involvement of the other. However, the vast majority of the evidence accumulated over the past several years indicates quite clearly that the major mediator is bradykinin. Therefore, unregulated contact system activation is the defect that leads directly to the development of angioedema. C1 Harvard Univ, Sch Med, Ctr Blood Res, Inst Biomed Res, Boston, MA 02115 USA. RP Davis, AE (reprint author), Harvard Univ, Sch Med, Ctr Blood Res, Inst Biomed Res, 800 Huntington Ave, Boston, MA 02115 USA. EM aldavis@cbrinstitute.org FU NIAID NIH HHS [AI057366]; NICHD NIH HHS [HD22082, HD33727] NR 107 TC 44 Z9 45 U1 1 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-8561 J9 IMMUNOL ALLERGY CLIN JI Immunol. Allerg. Clin. North Am. PD NOV PY 2006 VL 26 IS 4 BP 633 EP + DI 10.1016/j.iac.2006.08.003 PG 20 WC Allergy; Immunology SC Allergy; Immunology GA 111MU UT WOS:000242457100005 PM 17085282 ER PT J AU Banerji, A Weller, PF Sheikh, J AF Banerji, Aleena Weller, Peter F. Sheikh, Javed TI Cytokine-associated angioedema syndromes including episodic angioedema with eosinophilia (Gleich's syndrome) SO IMMUNOLOGY AND ALLERGY CLINICS OF NORTH AMERICA LA English DT Article ID CAPILLARY LEAK SYNDROME; ENDOTHELIAL-CELLS; SERUM-LEVELS; EDEMA; HYPEREOSINOPHILIA; SHOCK; INTERLEUKIN-2; PERMEABILITY; LYMPHOCYTES; ACTIVATION AB Of the various angioedema syndromes, some are thought to be cytokine-mediated. The authors review the cytokine-associated angioedema syndromes with a focus on episodic angioedema with eosinophilia (Gleich's Syndrome) and non-episodic angioedema with eosinophilia. NERDS (nodules, eosinophilia, rheumatism, dermatitis, and swelling), Clarkson Syndrome (idiopathic capillary leak syndrome), and angioedema associated with aldesleukin (human recombinant interleukin-2) and interferon-a are also discussed. There is still much to be learned about the pathophysiology, diagnosis, and treatment of patients with these disorders. C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Allergy & Inflammat, Boston, MA 02215 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA 02215 USA. RP Sheikh, J (reprint author), Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Allergy & Inflammat, 330 Brookline Ave,DA-617, Boston, MA 02215 USA. EM jsheikh@bidmc.harvard.edu NR 46 TC 20 Z9 21 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 0889-8561 J9 IMMUNOL ALLERGY CLIN JI Immunol. Allerg. Clin. North Am. PD NOV PY 2006 VL 26 IS 4 BP 769 EP + DI 10.1016/j.iac.2006.09.001 PG 14 WC Allergy; Immunology SC Allergy; Immunology GA 111MU UT WOS:000242457100013 PM 17085290 ER PT J AU Fujitani, S Ricardo-Dukelow, M Kamiya, T Sullivan, L Low, L AF Fujitani, Shigeki Ricardo-Dukelow, M. Kamiya, Toru Sullivan, Loretta Low, Lewis TI Ethnicity and other possible risk factors for candidemia at 3 tertiary care university hospitals in Hawaii SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID BLOOD-STREAM INFECTIONS; EPIDEMIOLOGY; SURVEILLANCE; TROPICALIS; FUNGEMIA; CANDIDIASIS; ALBICANS; PROGRAM; CANCER; ADULT AB A total of 108 cases of candidemia detected in 3 tertiary care university hospitals in Hawaii between January 2001 and December 2002 were retrospectively reviewed. Candida albicans, Candida glabrata, and Candida tropicalis accounted for 28% of the cases. Mortality among Filipino patients was significantly higher than that among other ethnic groups ( 71% vs 48%; P < .05). C1 VA Greater Los Angeles Healthcare Syst, Infect Dis Sect 111F, Dept Med, Los Angeles, CA 90073 USA. Univ Hawaii, Dept Med, Honolulu, HI 96822 USA. Legacy Hlth Syst, Dept Med, Portland, OR USA. RP Fujitani, S (reprint author), VA Greater Los Angeles Healthcare Syst, Infect Dis Sect 111F, Dept Med, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM shigekifujitani@hotmail.com NR 19 TC 5 Z9 5 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0899-823X J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD NOV PY 2006 VL 27 IS 11 BP 1261 EP 1263 DI 10.1086/508831 PG 3 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 205AG UT WOS:000249084500022 PM 17080389 ER PT J AU Miller, G Randolph, S Patterson, JE AF Miller, George Randolph, Stephen Patterson, Jan E. TI Responding to bioterrorist smallpox in San Antonio SO INTERFACES LA English DT Article DE health care : epidemiology; simulation : applications ID VACCINATION; LOGISTICS; OUTBREAKS; NETWORKS; MODEL AB We used discrete-event simulation to help the San Antonio public health and acute medical care communities to plan their response to a bioterrorist attack. The analysis, based on a scenario positing an attack with aerosolized smallpox, indicated the resources and strategies needed for an effective response. We found that a mixture of public-health measures designed to stop the spread of the disease would form a more robust and effective response than any single measure. However, unless the attack is very small, the public-health system is unlikely to be able to prevent a surge in demand for acute care that will require community-wide coordination of resources, a definitive patient-triage policy, and temporary treatment practices. The San Antonio communities are integrating our recommendations into their plans. C1 Altarum Inst, Ann Arbor, MI 48113 USA. Altarum Inst, San Antonio, TX 78209 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. RP Miller, G (reprint author), Altarum Inst, POB 134001, Ann Arbor, MI 48113 USA. EM george.miller@altarum.org; steve.randolph@altarum.org; pattersonj@uthscsa.edu NR 18 TC 17 Z9 19 U1 1 U2 2 PU INST OPERATIONS RESEARCH MANAGEMENT SCIENCES PI LINTHICUM HTS PA 901 ELKRIDGE LANDING RD, STE 400, LINTHICUM HTS, MD 21090-2909 USA SN 0092-2102 J9 INTERFACES JI Interfaces PD NOV-DEC PY 2006 VL 36 IS 6 BP 580 EP 590 DI 10.1287/inte.1060.0228 PG 11 WC Management; Operations Research & Management Science SC Business & Economics; Operations Research & Management Science GA 117JA UT WOS:000242868100010 ER PT J AU Zaid, AN Bowirrat, A Kort, JJ Oscar-Berman, M AF Zaid, A. -N. Bowirrat, A. Kort, J. J. Oscar-Berman, M. TI Bioequivalence study of two fluoxetine capsule formulations in healthy Middle Eastern volunteers SO INTERNATIONAL JOURNAL OF CLINICAL PHARMACOLOGY AND THERAPEUTICS LA English DT Article DE bioequivalence; fluoxetine; bioavailability; spectrophotometer; pharmacokinetics ID SEROTONIN REUPTAKE INHIBITORS; CLINICAL PHARMACOKINETICS; PHARMACOLOGY AB Objective: To assess the bioequivalence of two fluoxetine hydrochloride capsule (20 mg) formulations (Fluoxicare capsule from Pharmocare Ltd., Chemicals and Cosmetics, Ramallah, Palestine, as test formulation, and Prozac from Eli Lilly Ltd., Basingstoke, UK, as reference formulation). Design and methods: The study was conducted open with a randomized 2-period crossover design and a 6-week washout period. Participants were 24 healthy male volunteers aged 18 - 28 years, divided into 2 groups of 12 subjects. One group was given the originator drug (reference formulation), and the other was given the test formulation. Blood samples were obtained at baseline and at 14 time points during the interval 0 - 96 hours after drug administration. The concentrations of the samples were assayed spectrophotometrically at 220 nm using a Shimadzu 160 A UV-visible spectrometer. We calculated the plasma concentration-time curve (AUC), maximum plasma concentration (C-max), and time of maximum plasma concentration (t(max)) for each subject. Logarithmic transformation of the AUC and C-max was used for the statistical analyses and to assess the bioavailability of the two formulations, using analyses of variance (ANOVA) and Satherwait t-tests for unequal variances. The ANOVA performed Of t(max) in C-max, and in AUC provided the appropriate intra-subject variance estimates to evaluate the 90% confidence intervals for the differences between study variables after administration of the test and reference formulations. Statistical analyses were conducted on AUC(0-4) as the extrapolated part of the AUC, a truncated area approach was adapted. Results: The mean pharmacokinetic parameters for both of the drugs under study were as follows: C-max = 61.24 (+/- 12.96) ng/ml for the test formulation, and for the reference formulation C-max = 61.39 (+/- 14.1) ng/ml, the effects were statistically equivalent. The tmax for the test formulation was 8.25 (+/- 1.7) and 7.33 (+/- 0.96) for the reference formulation. The area under the curve to infinity (AUC(0-infinity) (ng, day/ml)) for the test formulation and for the reference formulation were 293.02 (+/- 52.69) and 296.15 (+/- 61.69), respectively. Conclusions: The two formulations had equivalent pharmacokinetic parameters, were well-tolerated, and their relative bioavailability was 98.94%. C1 Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Neurol & Anat, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Neurobiol, Boston, MA 02118 USA. Boston VA Healthcare Syst, Boston, MA USA. An Najah Natl Univ, Fac Pharm, Nablus, Israel. Galilee Soc, Reg Res & Dev Ctr, Shefa Amr, Israel. Pharmacare PLC Co, R&D Manager, Ramallah, Israel. RP Oscar-Berman, M (reprint author), Boston Univ, Sch Med, Dept Psychiat, L815 715 Albany St, Boston, MA 02118 USA. EM oscar@bu.edu FU NIAAA NIH HHS [R37-AA07112] NR 15 TC 1 Z9 1 U1 0 U2 1 PU DUSTRI-VERLAG DR KARL FEISTLE PI DEISENHOFEN-MUENCHEN PA BAHNHOFSTRASSE 9 POSTFACH 49, D-82032 DEISENHOFEN-MUENCHEN, GERMANY SN 0946-1965 J9 INT J CLIN PHARM TH JI Int. J. Clin. Pharmacol. Ther. PD NOV PY 2006 VL 44 IS 11 BP 593 EP 602 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 101BC UT WOS:000241712900009 PM 17176627 ER PT J AU Roach, M DeSilvio, M Valicenti, R Grignon, D Asbell, SO Lawton, C Thomas, CR Shipley, WU AF Roach, Mack, III DeSilvio, Michelle Valicenti, Richard Grignon, David Asbell, Sucha O. Lawton, Colleen Thomas, Charles R., Jr. Shipley, William U. TI Whole-pelvis, "mini-pelvis," or prostate-only external beam radiotherapy after neoadjuvant and concurrent hormonal therapy in patients treated in the Radiation Therapy Oncology Group 9413 trial SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE prostate cancer; randomized trials; radiation field size ID RANDOMIZED CONTROLLED-TRIAL; ANDROGEN SUPPRESSION; FOLLOW-UP; CANCER; DEPRIVATION; RISK AB Purpose: The Radiation Therapy Oncology Group (RTOG) 9413 trial demonstrated a better progression-free survival (PFS) with whole-pelvis (WP) radiotherapy (RT) compared with prostate-only (PO) RT. This secondary analysis was undertaken to determine whether "mini-pelvis" (MP; defined as >= 10 x 11cm but < 11 x 11cm) RT resulted in progression-free survival (PFS) comparable to that of WP RT. To avoid a timing bias, this analysis was limited to patients receiving neoadjuvant and concurrent hormonal therapy (N&CHT) in Arms I and 2 of the study. Methods and Materials: Eligible patients had a risk of lymph node (LN) involvement > 15%. Neoadjuvant and concurrent hormonal therapy (N&CHT) was administered 2 months before and during RT for 4 months. From April 1, 1995, to June 1, 1999, a group of 325 patients were randomized to WP RT + N&CHT and another group of 324 patients were randomized to receive PO RT + N&CHT. Patients randomized to PO RT were dichotomized by median field size (10 x 11cm), with the larger field considered an "MP" field and the smaller a PO field. Results: The median PFS was 5.2, 3.7, and 2.9 years for WP, MP, and PO fields, respectively (p = 0.02). The 7-year PFS was 40%, 35%, and 27% for patients treated to WP, MP, and PO fields, respectively. There was no association between field size and late Grade 3+ genitourinary toxicity but late Grade 3+ gastrointestinal RT complications correlated with increasing field size. Conclusions: This subset analysis demonstrates that RT field size has a major impact on PFS, and the findings support comprehensive nodal treatment in patients with a risk of LN involvement of > 15%. (c) 2006 Elsevier Inc. C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. RTOG Stat Headquarters, Philadelphia, PA USA. Thomas Jefferson Univ, Philadelphia, PA 19107 USA. Wayne State Univ, Detroit, MI USA. Albert Einstein Med Ctr, Philadelphia, PA 19141 USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. Oregon Hlth & Sci Univ, Portland, OR USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Roach, M (reprint author), Univ Calif San Francisco, 1600 Divisadero St,Suite H1031, San Francisco, CA 94143 USA. EM roach@radone17.ucsf.edu FU NCI NIH HHS [U10 CA37422, U10 CA32115, U10 CA21661] NR 17 TC 103 Z9 103 U1 0 U2 0 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 NOV 1 PY 2006 VL 66 IS 3 BP 647 EP 653 DI 10.1016/j.ijrobp.2006.05.074 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 094EI UT WOS:000241221900002 PM 17011443 ER PT J AU Kozak, KR Smith, BL Adams, J Kornmehl, E Katz, A Gadd, M Specht, M Hughes, K Gioioso, V Lu, HM Braaten, K Recht, A Powell, SN DeLaney, TF Taghian, AG AF Kozak, Kevin R. Smith, Barbara L. Adams, Judith Kornmehl, Ellen Katz, Angela Gadd, Michele Specht, Michelle Hughes, Kevin Gioioso, Valeria Lu, Hsiao-Ming Braaten, Kristina Recht, Abram Powell, Simon N. DeLaney, Thomas F. Taghian, Alphonse G. TI Accelerated partial-breast irradiation using proton beams: Initial clinical experience SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE breast cancer; cosmesis; partial-breast irradiation; protons; toxicity ID DOSE-RATE BRACHYTHERAPY; RADIATION-THERAPY; CONSERVING THERAPY; DOSIMETRIC EXPERIENCE; CANCER; RADIOTHERAPY; LUMPECTOMY; SURGERY; CARCINOMA; BONE AB Purpose: We present our initial clinical experience with proton, three-dimensional, conformal, external beam, partial-breast irradiation (3D-CPBI). Methods and Materials: Twenty patients with Stage I breast cancer were treated with proton 3D-CPBI in a Phase I/II clinical trial. Patients were followed at 3 to 4 weeks, 6 to 8 weeks, 6 months, and every 6 months thereafter for recurrent disease, cosmetic outcome, toxicity, and patient satisfaction. Results: With a median follow-up of 12 months (range, 8-22 months), no recurrent disease has been detected. Global breast cosmesis was judged by physicians to be good or excellent in 89% and 100% of cases at 6 months and 12 months, respectively. Patients rated global breast cosmesis as good or excellent in 100% of cases at both 6 and 12 months. Proton 3D-CPBI produced significant acute skin toxicity with moderate to severe skin color changes in 79% of patients at 3 to 4 weeks and moderate to severe moist desquamation in 22% of patients at 6 to 8 weeks. Telangiectasia was noted in 3 patients. Three patients reported rib tenderness in the treated area, and one rib fracture was documented. At last follow-up, 95% of patients reported total satisfaction with proton 3D-CPBI. Conclusions: Based on our study results, proton 3D-CPBI offers good-to-excellent cosmetic outcomes in 89% to 100% of patients at 6-month and 12-month follow-up and nearly universal patient satisfaction. However, proton 3D-CPBI, as used in this study, does result in significant acute skin toxicity and may potentially be associated with late skin (telangiectasia) and rib toxicity. Because of the dosimetric advantages of proton 3D-CPBI, technique modifications are being explored to improve acute skin tolerance. (c) 2006 Elsevier Inc. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Surg Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Dept Radiat Oncol, Boston, MA 02215 USA. RP Taghian, AG (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, 100 Blossom St,COX-3, Boston, MA 02114 USA. EM ataghian@partners.org OI Hughes, Kevin/0000-0003-4084-6484 FU NCI NIH HHS [P50 CA89393, P01 CA21239] NR 31 TC 71 Z9 72 U1 0 U2 4 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 NOV 1 PY 2006 VL 66 IS 3 BP 691 EP 698 DI 10.1016/j.ijrobp.2006.06.041 PG 8 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 094EI UT WOS:000241221900009 PM 17011445 ER PT J AU Singhal, AB AF Singhal, Aneesh B. TI Oxygen therapy in stroke: past, present, and future SO INTERNATIONAL JOURNAL OF STROKE LA English DT Review DE acute stroke therapy; hyperbaric oxygen therapy; neuroprotection; normobaric oxygen therapy; oxygen toxicity ID FOCAL CEREBRAL-ISCHEMIA; RANDOMIZED CONTROLLED-TRIAL; ACUTE MYOCARDIAL-INFARCTION; FREE-RADICAL PRODUCTION; GLOBAL BRAIN ISCHEMIA; SPINAL-CORD ISCHEMIA; HYPERBARIC-OXYGEN; RAT MODEL; NORMOBARIC HYPEROXIA; ARTERY OCCLUSION AB Oxygen is frequently administered to patients with suspected stroke. However, the role of oxygen therapy in ischemic stroke remains controversial in light of the failure of three clinical trials of hyperbaric oxygen therapy to show efficacy, and the fear of exacerbating oxygen free radical injury. The previous trials had several shortcomings, perhaps because they were designed on basis of anecdotal case reports and little preclinical data. Most animal studies concerning oxygen therapy in stroke have been conducted over the last 6 years. Emerging data suggests that hyperbaric and even normobaric oxygen therapy can be effective if used appropriately, and raises the tantalizing possibility that hyperoxia can be used to extend the narrow therapeutic time window for stroke thrombolysis. This article reviews the history, rationale, mechanisms of action and adverse effects of hyperoxia, the key results of previous hyperoxia studies, and the potential role of oxygen therapy in contemporary stroke treatment. C1 Massachusetts Gen Hosp, Ctr Stroke Res, Boston, MA 02114 USA. RP Singhal, AB (reprint author), Massachusetts Gen Hosp, Ctr Stroke Res, 175 Cambridge St,Suite 300, Boston, MA 02114 USA. EM asinghal@partners.org NR 116 TC 26 Z9 27 U1 0 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1747-4930 J9 INT J STROKE JI Int. J. Stroke PD NOV PY 2006 VL 1 IS 4 BP 191 EP 200 DI 10.1111/j.1747-4949.2006.00058.x PG 10 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 178DO UT WOS:000247201600003 PM 18706016 ER PT J AU Farhat, M Greenaway, C Pai, M Menzies, D AF Farhat, M. Greenaway, C. Pai, M. Menzies, D. TI False-positive tuberculin skin tests: what is the absolute effect of BCG and non-tuberculous mycobacteria? SO INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE LA English DT Review DE tuberculin skin test; latent TB infection; atypical mycobacteria; environmental mycobacteria; nontuberculous mycobacteria; BCG vaccination ID CALMETTE-GUERIN VACCINATION; INTERFERON-GAMMA ASSAY; HEALTH-CARE WORKERS; SWEDISH CHILDREN; YOUNG-ADULTS; SENSITIVITY; INFECTION; PREVALENCE; SCHOOLCHILDREN; REACTIVITY AB BACKGROUND: Despite certain drawbacks, the tuberculin skin test (TST) remains in widespread use. Important advantages of the TST are its low cost, simplicity and interpretation based on extensive published literature. However, TST specificity is reduced by bacille Calmette-Guerin (BCG) vaccination and exposure to non-tuberculous mycobacteria (NTM). METHODS: To estimate TST specificity, we reviewed the published literature since 1966 regarding the effect of BCG vaccination and NTM infection on TST. Studies selected included healthy subjects with documented BCG vaccination status, including age at vaccination. Studies of NTM effect had used standardised NTM antigens in healthy subjects. RESULTS: In 24 studies involving 240203 subjects BCG-vaccinated as infants, 20 406 (8.5%) had a TST of 10+ mm attributable to BCG, but only 56/5639 (1%) were TST-positive if tested >= 10 years after BCG. In 12 studies of 12 728 subjects vaccinated after their first birthday, 5314 (41.8%) had a false-positive TST of 10+ mm, and 191/898 (21.2%) after 10 years. Type of tuberculin test did not modify these results. In 18 studies involving 1169 105 subjects, the absolute prevalence of false-positive TST from NTM cross-reactivity ranged from 0.1% to 2.3% in different regions. CONCLUSIONS: The effect on TST of BCG received in infancy is minimal, especially >= 10 years after vaccination. BCG received after infancy produces more frequent, more persistent and larger TST reactions. NTM is not a clinically important cause of false-positive TST, except in populations with a high prevalence of NTM sensitisation and a very low prevalence of TB infection. C1 McGill Univ, Montreal Chest Inst, Resp Epidemiol & Clin Res Unit, Montreal, PQ H2X 2P4, Canada. Harvard Univ, Massachusetts Gen Hosp, Boston, MA USA. McGill Univ, SMBD Jewish Gen Hosp, Div Infect Dis & Microbiol, Montreal, PQ, Canada. McGill Univ, Joint Dept Epidemiol & Biostat, Montreal, PQ, Canada. McGill Univ, Joint Dept Occupat Hlth, Montreal, PQ, Canada. RP Menzies, D (reprint author), McGill Univ, Montreal Chest Inst, Resp Epidemiol & Clin Res Unit, 3650 St Urbain,Rm K1 24, Montreal, PQ H2X 2P4, Canada. EM dick.menzies@mcgill.ca NR 79 TC 311 Z9 318 U1 2 U2 9 PU INT UNION AGAINST TUBERCULOSIS LUNG DISEASE (I U A T L D) PI PARIS PA 68 BOULEVARD SAINT-MICHEL,, 75006 PARIS, FRANCE SN 1027-3719 J9 INT J TUBERC LUNG D JI Int. J. Tuberc. Lung Dis. PD NOV PY 2006 VL 10 IS 11 BP 1192 EP 1204 PG 13 WC Infectious Diseases; Respiratory System SC Infectious Diseases; Respiratory System GA 099RA UT WOS:000241611800003 PM 17131776 ER PT J AU Gragoudas, ES AF Gragoudas, Evangelos S. TI Proton beam irradiation of uveal melanomas: The first 30 years - The Weisenfeld Lecture SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Review ID COLLABORATIVE OCULAR MELANOMA; HELIUM ION THERAPY; LARGE CHOROIDAL MELANOMA; COMS RANDOMIZED-TRIAL; METASTATIC MELANOMA; PROGNOSTIC-FACTORS; TUMOR-CONTROL; IODINE-125 BRACHYTHERAPY; RADIATION COMPLICATIONS; INTRAOCULAR MELANOMA AB The earliest treatment for uveal melanoma was removal of the eye. Today, enucleation has been supplanted by radiotherapy as the standard of care for patients with uveal melanoma, offering patients preservation of an intact eye and, in many cases, preservation of visual function. Enucleation is usually indicated for tumors with large extrascleral extensions and extensive iris neovascularization or tumors involving more than 30% of the ocular volume. Other treatment modalities, such as local resection and transpupillary thermotherapy, are used in a few centers in selected cases. C1 Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Retina Serv,Dept Ophthalmol, Boston, MA 02114 USA. RP Gragoudas, ES (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Retina Serv,Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM evangelos_gragoudas@meei.harvard.edu NR 104 TC 47 Z9 47 U1 0 U2 4 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD NOV PY 2006 VL 47 IS 11 BP 4666 EP 4673 DI 10.1167/iovs.06-0659 PG 8 WC Ophthalmology SC Ophthalmology GA 098XS UT WOS:000241557500004 PM 17065472 ER PT J AU Barrett, BJ Katzberg, RW Thomsen, HS Chen, N Sahani, D Soulez, G Heiken, JP Lepanto, L Ni, ZH Nelson, R AF Barrett, Brendan J. Katzberg, Richard W. Thomsen, Henrik S. Chen, Nan Sahani, Dushyant Soulez, Gilles Heiken, Jay P. Lepanto, Luigi Ni, Zhou-Hui Nelson, Rendon TI Contrast-induced nephropathy in patients with chronic kidney disease undergoing computed tomography - A double-blind comparison of iodixanol and iopamidol SO INVESTIGATIVE RADIOLOGY LA English DT Article DE chronic kidney disease; contrast media; contrast-induced nephropathy; computed tomography ID HIGH-RISK PATIENTS; AGENT-ASSOCIATED NEPHROTOXICITY; RANDOMIZED CONTROLLED-TRIAL; PREEXISTING RENAL-INSUFFICIENCY; N-ACETYLCYSTEINE; CORONARY-ANGIOGRAPHY; RADIOGRAPHIC-CONTRAST; UROGENITAL-RADIOLOGY; ORAL ACETYLCYSTEINE; EUROPEAN-SOCIETY AB Background: Based on a single clinical trial, it has been suggested that the contrast agent iodixanol, which is isotonic to human plasma, may be less nephrotoxic than other nonionic contrast agents in renally impaired patients after intra-arterial injection. We compared the effects on renal function of iopamidol-370 injection (796 mOsm/kg) and iodixanol-320 (290 mOsm/kg) in patients with chronic kidney disease undergoing contrast-enhanced multidetector computed tomography (CE-MDCT) examinations using a multicenter, double-blind, randomized, parallel-group design. Methods: A total of 166 patients with stable moderate-to-severe chronic kidney disease (screening and baseline serum creatinine, SCr, >= 1.5 mg/dL and/or creatinine clearance, CrCl, <= 60 mL/min) who were undergoing CE-MDCT of the liver or peripheral arteries were randomized to receive equi-iodine IV doses (40 gI) of either iopamidol-370 (370 mgI/mL) or iodixanol-320 (320 mgI/mL) at 4 mL/s. SCr and CrCl were obtained at screening, baseline, and at 48-72 +/- 6 hours after dose (mean, 57.4 hours). Contrast-induced nephropathy (CIN) was defined as an absolute increase >= 0.5 mg/dL (44.2 mu mol/L) and/or a relative increase in SCr >= 25% from baseline. Results: A total of 153 patients were included in the final analysis (13 patients excluded because of lack of follow-up, hemodialysis to remove contrast, average daily CrCl variation > 1% at screening). The 2 study groups were comparable with regard to age, gender distribution, the presence of diabetes, concomitant medications, hydration, and contrast dose. Mean predose SCr was 1.6 +/- 0.4 mg/dL in both groups (P = 0.9). An absolute increase >= 0.5 mg/dL (44.2 mu mol/L) in SCr was observed in none of the patients receiving iopamidol-370 and in 2.6% (2/76) of patients receiving iodixanol-320 (95% confidence interval -6.2, 1.0, P = 0.2). A relative increase >= 25% in SCr occurred in 4% (3/77) of patients receiving iopamidol-370 and in 4% (3/76) of the patients receiving iodixanol-320 (95% confidence interval -6.2, 6.1, P = 1.0). Conclusion: The rate of CIN was similarly low in risk patients after intravenous administration of iopamidol-370 or iodixanol-320 for CE-MDCT. C1 Hlth Sci Ctr, Patient Res Ctr, St John, NF A1B 3V6, Canada. Univ Calif, Davis Med Ctr, Dept Radiol, Sacramento, CA USA. Herlev Univ Hosp, Dept Diagnost Radiol, Herlev, Denmark. Rui Jin Hosp, Dept Nephrol, Shanghai, Peoples R China. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. CHUM, Dept Radiol, Montreal, PQ, Canada. Washington Univ, Sch Med, Dept Radiol, St Louis, MO 63110 USA. Ren Ji Hosp, Dept Nephrol, Shanghai, Peoples R China. Duke Univ, Ctr Med, Dept Radiol, Durham, NC 27706 USA. RP Barrett, BJ (reprint author), Hlth Sci Ctr, Patient Res Ctr, 300 Prince Philip Dr, St John, NF A1B 3V6, Canada. EM bbarrett@mun.ca OI soulez, gilles/0000-0002-5566-3552 NR 45 TC 135 Z9 141 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0020-9996 J9 INVEST RADIOL JI Invest. Radiol. PD NOV PY 2006 VL 41 IS 11 BP 815 EP 821 DI 10.1097/01.rli.0000242807.01818.24 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 100RZ UT WOS:000241687700006 PM 17035872 ER PT J AU Servoss, JC Kitch, DW Andersen, JW Reisler, RB Chung, RT Robbins, GK AF Servoss, Julie C. Kitch, Douglas W. Andersen, Janet W. Reisler, Ronald B. Chung, Raymond T. Robbins, Gregory K. TI Predictors of antiretroviral-related hepatotoxicity in the Adult AIDS Clinical Trial Group (1989-1999) SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE antiretroviral therapy; hepatitis C virus; hepatotoxicity; HIV; liver disease ID RISK-FACTORS; HEPATITIS-C; THERAPY; INFECTION; VIRUS AB HIV antiretroviral therapy (ART)-related hepatotoxicity is a significant clinical problem, resulting in severe elevations of liver enzymes and, potentially, liver failure and death. We retrospectively determined baseline clinical predictors of severe hepatotoxicity (SH; serum aminotransferases or total bilirubin > 5 times and > 2.5 times the upper limit of normal [ULN], respectively) among 8851 subjects enrolled in 16 Adult AIDS Clinical Trial Group studies from October 1989 to June 1999. Subjects were divided into the following treatment categories: single nucleoside reverse transcriptase inhibitors (NRTIs), multiple NRTIs, normucleoside reverse transcriptase inhibitors (NNRTls) combined with NRTIs, and the protease inhibitor (PI) indinavir (IDV) combined with NRTIs. SH occurred in 824 (9.3%) subjects, in 613 (6.92%) in the first 6 months and in another 211(2.38%) in the subsequent 6 months of study ART. Consistent with other reports, baseline elevation in serum aminotransferases was a significant risk factor for SH for all regimens. Risk factors not previously identified included concomitant hepatotoxic medications, thrombocytopenia, and renal insufficiency. Hepatitis C virus coinfection was associated with an increased risk of SH (odds ratio [OR] = 2.7; P < 0.003). In conclusion, this study identified known and previously unreported risk factors for severe hepatotoxicity that should be considered before the initiation of ART. C1 Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Stat & Data Anal Ctr, Boston, MA 02115 USA. Univ Maryland, Sch Med, Inst Human Virol, Baltimore, MD 21201 USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. RP Chung, RT (reprint author), Massachusetts Gen Hosp, Gastrointestinal Unit, GRJ-825,55 Fruit St, Boston, MA 02114 USA. EM rtchung@partners.org FU NIAID NIH HHS [AI-38855, AI-38858] NR 9 TC 45 Z9 45 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD NOV 1 PY 2006 VL 43 IS 3 BP 320 EP 323 DI 10.1097/01.qai.0000243054.58074.59 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 099KB UT WOS:000241592000009 PM 16967041 ER PT J AU Fraguas, R Henriques, SG De Lucia, MS Iosifescu, DV Schwartz, FH Menezes, PR Gattaz, WF Martins, MA AF Fraguas, Renerio, Jr. Henriques, Sergio Gonsalves, Jr. De Lucia, Mara S. Iosifescu, Dan V. Schwartz, Faye H. Menezes, Paulo Rossi Gattaz, Wagner Fanid Martins, Milton Arruda TI The detection of depression in medical setting: A study with PRIME-MD (vol 91, pg 11, 2006) SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Correction C1 Univ Sao Paulo, Fac Med, Dept & Inst Psychiat, BR-05508 Sao Paulo, Brazil. Harvard Univ, Massachusetts Gen Hosp, Depress Clin & Res Program, Cambridge, MA 02138 USA. Univ Sao Paulo, Fac Med, Hosp Clin, Cent Inst,Div Psychol, BR-05508 Sao Paulo, Brazil. Univ Sao Paulo, Fac Med, Dept Prevent Med, BR-05508 Sao Paulo, Brazil. Univ Sao Paulo, Fac Med, Dept Gen Med, BR-05508 Sao Paulo, Brazil. RP Fraguas, R (reprint author), Univ Sao Paulo, Fac Med, Dept & Inst Psychiat, BR-05508 Sao Paulo, Brazil. EM rfraguas@partners.org RI Gattaz, Wagner/C-4456-2012; Martins, Milton/D-6658-2012 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 0165-0327 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD NOV PY 2006 VL 96 IS 1-2 BP 139 EP 139 DI 10.1016/j.jd.2006.05.010 PG 1 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 104BM UT WOS:000241930900020 ER PT J AU Garrow, D Egede, LE AF Garrow, Donald Egede, Leonard E. TI National patterns and correlates of complementary and alternative medicine use in adults with diabetes SO JOURNAL OF ALTERNATIVE AND COMPLEMENTARY MEDICINE LA English DT Article ID UNITED-STATES; PREVALENCE; RELIABILITY; ASSOCIATION; THERAPIES; MELLITUS; SERVICES; COSTS AB Objective: The aim of this study was to determine national patterns and correlates of complementary and alternative medicine (CAM) use among adults with diabetes. Methods: The authors compared CAM use in 2474 adults with and 28,625 adults without diabetes who participated in the most comprehensive national survey on CAM use (2002 National Health Interview Survey). Eight CAM use categories were created, including dietary, herbal, chiropractic, yoga, relaxation, vitamin, prayer, and other (acupuncture, Ayurveda, biofeedback, chelation, energy healing or Reiki therapy, hypnosis, massage, naturopathy, and homeopathy). An overall CAM use category also was created that excluded vitamins and prayer. Patterns of use were compared with chi-square and independent correlates of CAM use with multiple logistic regression controlling for relevant covariates. STATA was used for analysis to account for the complex survey design. Results: Prevalence of overall use of CAM did not differ significantly by diabetes status (47.6 versus 47.9%, p = 0.81). Diabetes was not an independent predictor of overall use of CAM (OR 0.93, 95% confidence interval [CI] 0.83, 1.05). However, persons with diabetes were more likely to use prayer (OR 1.19, 95% Cl 1.05, 1.36), but less likely to use herbs (OR 0.86, 95% Cl 0.75, 0.99), yoga (OR 0.56, 95% Cl 0.43, 0.72), or vitamins (OR 0.82, 95% Cl 0.72, 0.93) than people without diabetes after controlling for relevant covariates. Independent correlates of overall use of CAM differed by age, income, employment, comorbidity, and health status between people with and without diabetes. Conclusions: This study found that there has been a dramatic increase in overall use of CAM in adults with diabetes; diabetes was not an independent predictor of overall use of CAM; and people with diabetes were more likely to use prayer, but less likely to use herbs, yoga, or vitamins compared to persons without diabetes. C1 Med Univ S Carolina, Ctr Hlth Dispar Res, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Med, Div Gen Internal Med, Charleston, SC 29425 USA. Ralph H Johnson Vet Adm Med Ctr, Charleston VA TREP, Charleston, SC USA. RP Egede, LE (reprint author), Med Univ S Carolina, Ctr Hlth Dispar Res, 135 Rutledge Ave,Room 280H, Charleston, SC 29425 USA. EM egedel@musc.edu NR 29 TC 36 Z9 36 U1 4 U2 15 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 NOV PY 2006 VL 12 IS 9 BP 895 EP 902 DI 10.1089/acm.2006.12.895 PG 8 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 104MW UT WOS:000241963500010 PM 17109581 ER PT J AU Levine, S Nguyen, T Friscia, M Zhu, JL Szeto, W Kucharczuk, JC Tikunov, BA Rubinstein, NA Kaiser, LR Shrager, JB AF Levine, Sanford Nguyen, Taitan Friscia, Michael Zhu, Jianliang Szeto, Wilson Kucharczuk, John C. Tikunov, Boris A. Rubinstein, Neal A. Kaiser, Larry R. Shrager, Joseph B. TI Parasternal intercostal muscle remodeling in severe chronic obstructive pulmonary disease SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE muscle fiber types; myosin heavy chain isoform expression; diaphragm ID RAT SKELETAL-MUSCLE; HUMAN DIAPHRAGM; GENE-EXPRESSION; SEVERE COPD; FIBER SIZE; MYOSIN; ACTIVATION; VOLUME; DRIVE; STIMULATION AB Studies in experimental animals indicate that chronic increases in neural drive to limb muscles elicit a fast-to-slow transformation of fiber-type proportions and myofibrillar proteins. Since neural drive to the parasternal intercostal muscles (parasternals) is chronically increased in patients with severe chronic obstructive pulmonary diseases (COPDs), we carried out the present study to test the hypothesis that the parasternals of COPD patients exhibit an increase in the proportions of both slow fibers and slow myosin heavy chains (MHCs). Accordingly, we obtained full thickness parasternal muscle biopsies from the third interspace of seven COPD patients (mean +/- SE age: 59 +/- 4 yr) and seven age-matched controls (AMCs). Fiber typing was done by immunohistochemistry, and MHC proportions were determined by SDS-PAGE followed by densitometry. COPD patients exhibited higher proportions of slow fibers than AMCs (73 +/- 4 vs. 51 +/- 3%; P < 0.01). Additionally, COPD patients exhibited higher proportions of slow MHC than AMCs (56 +/- 4 vs. 46 +/- 4%, P < 0.04). We conclude that the parasternal muscles of patients with severe COPD exhibit a fast-to-slow transformation in both fiber-type and MHC proportions. Previous workers have demonstrated that remodeling of the external intercostals, another rib cage inspiratory muscle, elicited by severe COPD is characterized by a slow-to-fast transformation in both fiber types and MHC isoform proportions. The physiological significance of this difference in remodeling between these two inspiratory rib cage muscles remains to be elucidated. C1 Univ Penn, Sch Med, Dept Surg, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Cell & Dev Biol, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Surg & Res Serv, Philadelphia, PA USA. Univ Penn, Dept Biol, Philadelphia, PA 19104 USA. RP Levine, S (reprint author), Hosp Univ Penn, Div Thorac Surg, 6 Silverstein Pavil,3400 Spruce St, Philadelphia, PA 19104 USA. EM sdlevine@mail.med.upenn.edu NR 36 TC 18 Z9 20 U1 2 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD NOV PY 2006 VL 101 IS 5 BP 1297 EP 1302 DI 10.1152/japplphysiol.01607.2005 PG 6 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 107GS UT WOS:000242159300007 PM 16777998 ER PT J AU Awdeh, ZL Yunis, EJ Audeh, MJ Fici, D Pugliese, A Larsen, CE Alper, CA AF Awdeh, Z. L. Yunis, Edmond J. Audeh, Mark J. Fici, Dolores Pugliese, Alberto Larsen, Charles E. Alper, Chester A. TI A genetic explanation for the rising incidence of type 1 diabetes, a polygenic disease SO JOURNAL OF AUTOIMMUNITY LA English DT Article DE type 1 diabetes; rising incidence of type 1 diabetes; excess heterozygosity ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; HL-A ANTIGENS; INSULIN GENE; ENCODED SUSCEPTIBILITY; INCREASING INCIDENCE; CELIAC-DISEASE; MELLITUS; POPULATION; IDDM; INHERITANCE AB We had earlier hypothesized, if parents originated from previously isolated populations that had selected against different critical susceptibility genes for a polygenic disease, their offspring could have a greater risk of that disease than either parent. We therefore studied parents of patients with type I diabetes (T I D). We found that parents who transmitted HLA-DR3 to HLA-DR3/DR4 patients had different HLA-A allele frequencies on the non-transmitted HLA haplotype than HLA-DR4-transmitters. HLA-DR3-positive parents also had different insulin (INS) gene allele frequencies than HLA-DR4-positive parents. Parent pairs of patients had greater self-reported ethnicity disparity than parent pairs in control families. Although there was an excess of HLA-DR3/DR4 heterozygotes among type I diabetes patients, there were significantly fewer HLA-DR3/DR4 heterozygous parents of patients than expected. These findings are consistent with HLA-DR and INS VNTR alleles marking both disease susceptibility and separate Caucasian parental subpopulations. Our hypothesis thus explains some seemingly disconnected puzzling phenomena, including (1) the rising world-wide incidence of T I D, (2) the excess of HLA-DR3/DR4 heterozygotes among patients, (3) the changing frequency of HLA-DR3/DR4 heterozygotes and of susceptibility alleles in general in patients over the past several decades, and (4) the association of INS alleles with specific HLA-DR alleles in patients with T1D. (c) 2006 Elsevier Ltd. All rights reserved. C1 CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Boston Coll, Boston, MA 02467 USA. Univ Miami, Sch Med, Diabetes Res Inst, Miami, FL 33101 USA. Pulsat Clin Technol Inc, Cambridge, MA 02138 USA. RP Awdeh, ZL (reprint author), CBR Inst Biomed Res, 800 Huntington Ave, Boston, MA 02115 USA. EM awdeh@cbr.med.harvard.edu FU NCRR NIH HHS [RR021294]; NHLBI NIH HHS [HL29583] NR 53 TC 28 Z9 28 U1 1 U2 6 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0896-8411 J9 J AUTOIMMUN JI J. Autoimmun. PD NOV PY 2006 VL 27 IS 3 BP 174 EP 181 DI 10.1016/j.jaut.2006.08.004 PG 8 WC Immunology SC Immunology GA 111EZ UT WOS:000242435500005 PM 17052889 ER PT J AU Burroughs, BR Rubash, HE Estok, D Jasty, M Krevolin, J Muratoglu, OK AF Burroughs, Brian R. Rubash, Harry E. Estok, Daniel Jasty, Murali Krevolin, Janet Muratoglu, Orhun K. TI Comparison of conventional and highly crosslinked UHMWPE patellae evaluated by a new in vitro patellofemoral joint simulator SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS LA English DT Article DE UHMWPE; patallae; wear; oxidation ID MOLECULAR-WEIGHT POLYETHYLENE; TOTAL KNEE ARTHROPLASTY; BIOMECHANICAL ANALYSIS; STAIR ASCENT; MOMENT ARMS; WEAR; EXTENSION; REPLACEMENTS; VIVO; DEGRADATION AB A series of in vitro patella damage tests were developed using a knee simulator to investigate electron-beam-irradiated and -melted ultra-high molecular weight polyethylene and conventional ultra-high molecular weight polyethylene at the patellofemoral articulation. Three different simulations were created: (i) normal gait with optimal component alignment, (ii) stair climbing with optimal component alignment, and (iii) stair climbing with 4 degrees of femoral component internal rotation to simulate a component mallalignment condition. In the last two simulations, all patellae were artificially aged. In normal gait, the unaged conventional and highly crosslinked patellae demonstrated similar behavior. In both stair climbing tests, unlike the aged highly crosslinked components, the aged conventional patellae developed cracks by 2 million cycles. These results demonstrate the potential advantage of highly crosslinked polyethylene for the patella. (c) 2006 Wiley Periodicals, Inc. C1 Massachusetts Gen Hosp, Orthoped Biomech & Biomat Lab, Boston, MA 02114 USA. Zimmer, Austin, TX USA. RP Muratoglu, OK (reprint author), Massachusetts Gen Hosp, Orthoped Biomech & Biomat Lab, Boston, MA 02114 USA. EM omuratoglu@partners.org NR 41 TC 11 Z9 13 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4973 J9 J BIOMED MATER RES B JI J. Biomed. Mater. Res. Part B PD NOV PY 2006 VL 79B IS 2 BP 268 EP 274 DI 10.1002/jbm.b.30538 PG 7 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 098GK UT WOS:000241508800009 PM 16637026 ER PT J AU Carp, SA Kauffman, T Fang, QQ Rafferty, E Moore, R Kopans, D Boas, D AF Carp, Stefan A. Kauffman, Tina Fang, Qianqian Rafferty, Elizabeth Moore, Richard Kopans, Daniel Boas, David TI Compression-induced changes in the physiological state of the breast as observed through frequency domain photon migration measurements SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE spectroscopy; mammography; frequency domain; photon migration; breast cancer; oxygen consumption; blood flow; mammographic compression; diffuse reflection ID POSITRON EMISSION TOMOGRAPHY; SCATTERING MEDIA; BLOOD-FLOW; SPECTROSCOPY; PRESSURE; CANCER; TISSUE AB We use optical spectroscopy to characterize the influence of mammographic-like compression on the physiology of the breast. We note a reduction in total hemoglobin content, tissue oxygen saturation, and optical scattering under compression. We also note a hyperemic effect during repeated compression cycles. By modeling the time course of the tissue oxygen saturation, we are able to obtain estimates for the volumetric blood flow (1.64 +/- 0.6 mL/100 mL/min) and the oxygen consumption (1.97 +/- 0.6 mu mol/100 mL/min) of compressed breast tissue. These values are comparable to estimates obtained from previously published positron emission tomography (PET) measurements. We conclude that compression-induced changes in breast physiological properties are significant and should be accounted for when performing optical breast imaging. Additionally, the dynamic characteristics of the changes in breast physiological parameters, together with the ability to probe the tissue metabolic state, may prove useful for breast cancer detection. (c) 2006 Society of Photo-Optical Instrumentation Engineers. C1 Harvard Univ, Athinoula Martinos Ctr Biol Imaging, Massachusetts Gen Hosp, Sch Med, Charlestown, MA 02129 USA. RP Carp, SA (reprint author), Harvard Univ, Athinoula Martinos Ctr Biol Imaging, Massachusetts Gen Hosp, Sch Med, 13th St,Bldg 149,Room 2301, Charlestown, MA 02129 USA. EM carp@nmr.mgh.harvard.edu FU NCI NIH HHS [R01-CA97305, U54-CA104580] NR 18 TC 35 Z9 36 U1 0 U2 4 PU SPIE-SOC PHOTOPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD NOV-DEC PY 2006 VL 11 IS 6 AR 064016 DI 10.1117/1.2397572 PG 6 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 132UU UT WOS:000243968700019 PM 17212539 ER PT J AU Huppert, TJ Hoge, RD Dale, AM Franceschini, MA Boas, DA AF Huppert, Theodore J. Hoge, Rick D. Dale, Anders M. Franceschini, Maria A. Boas, David A. TI Quantitative spatial comparison of diffuse optical imaging with blood oxygen level-dependent and arterial spin labeling-based functional magnetic resonance imaging SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE near infrared; multimodality imaging; image reconstruction; magnetic resonance imaging ID NEAR-INFRARED SPECTROSCOPY; BRAIN ACTIVATION; CEREBRAL-BLOOD; BOLD SIGNAL; IN-VIVO; FOREPAW STIMULATION; LIGHT-PROPAGATION; RESPONSE FUNCTION; BALLOON MODEL; FMRI AB Akin to functional magnetic resonance imaging (fMRI), diffuse optical imaging (DOI) is a noninvasive method for measuring localized changes in hemoglobin levels within the brain. When combined with fMRI methods, multimodality approaches could offer an integrated perspective on the biophysics, anatomy, and physiology underlying each of the imaging modalities. Vital to the correct interpretation of such studies, control experiments to test the consistency of both modalities must be performed. Here, we compare DOI with blood oxygen level-dependent (BOLD) and arterial spin labeling fMRI-based methods in order to explore the spatial agreement of the response amplitudes recorded by these two methods. Rather than creating optical images by regularized, tomographic reconstructions, we project the fMRI image into optical measurement space using the optical forward problem. We report statistically better spatial correlation between the fMRI-BOLD response and the optically measured deoxyhemoglobin (R = 0.71, p = 1 X 10(-7)) than between the BOLD and oxyhemoglobin or total hemoglobin measures (R = 0.38, p = 0.04 vertical bar 0.37, p = 0.05, respectively). Similarly, we find that the correlation between the ASL measured blood flow and optically measured total and oxyhemoglobin is stronger (R = 0.73, p = 5 X 10(-6) and R = 0.71, p = 9 X 10(-6), respectively) than the flow to deoxyhemoglobin spatial correlation (R = 0.26, p = 0.10). (c) 2006 Society of Photo-Optical Instrumentation Engineers. C1 Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. Harvard Univ, Grad Program Biophys, Boston, MA 02115 USA. Univ Montreal, Unite Neuroimagerie Fonct, Ctr Rech Univ Geriatrie Montreal, Montreal, PQ, Canada. Univ Montreal, Dept Physiol, Montreal, PQ, Canada. Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. Univ Calif San Diego, Dept Radiol, La Jolla, CA 92093 USA. Univ Calif San Diego, Dept Cognit Sci, La Jolla, CA 92093 USA. RP Huppert, TJ (reprint author), Massachusetts Gen Hosp, AA Martinos Ctr Biomed Imaging, 13th St Bldg 149 Charlestown Navy Yard, Charlestown, MA 02129 USA. EM thuppert@nmr.mgh.harvard.edu RI Dale, Anders/A-5180-2010 FU NCRR NIH HHS [P41 RR014075-106006, P41 RR014075, P41 RR014075-086776, P41 RR014075-098612]; NIBIB NIH HHS [R01 EB000790, R01 EB001954, R01 EB001954-05, R01 EB002482, R01 EB002482-02, R01 EB002482-03, R01-EB001954, R01-EB002482] NR 65 TC 11 Z9 11 U1 0 U2 6 PU SPIE-INT SOCIETY OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD NOV-DEC PY 2006 VL 11 IS 6 AR 05335RR DI 10.1117/1.2400910 PG 16 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 132UU UT WOS:000243968700021 PM 17212541 ER PT J AU Levitt, JM Baldwin, A Papadakis, A Puri, S Xylas, J Munger, K Georgakoudi, I AF Levitt, Jonathan M. Baldwin, Amy Papadakis, Antonios Puri, Sameer Xylas, Joanna Munger, Karl Georgakoudi, Irene TI Intrinsic fluorescence and redox changes associated with apoptosis of primary human epithelial cells SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE fluorescence; apoptosis; optical diagnosis; microscopy; redox ratio ID LASER-INDUCED FLUORESCENCE; IN-VIVO; MITOCHONDRIAL-FUNCTION; BARRETTS-ESOPHAGUS; SPECTROSCOPY; AUTOFLUORESCENCE; CANCER; DIAGNOSIS; HETEROGENEITY; LOCALIZATION AB Apoptosis plays a key role in the development and maintenance of human tissues. This process has been studied traditionally in cells that are stained with exogenous fluorophores. These approaches affect cell viability, and thus are ill-suited for in vivo applications. We present an imaging approach that can identify apoptotic cells in living cell populations based on detection and quantification of distinct changes in the intensity and localization of cellular autofluorescence. Specifically, we acquire NAD(P)H, FAD, and redox ratio autofluorescence images of primary keratinocytes following 1, 9, 14, and 18 h of treatment with cisplatin, a known apoptosis-inducing chemotherapy agent. We find that intense autofluorescence combined with a low redox fluorescence ratio is progressively confined to a gradually smaller perinuclear cytoplasmic region with cisplatin treatment. Studies with exogenous nuclear fluorophores demonstrate that these autofluorescence changes occur at early stages of apoptosis. Additional costaining experiments suggest that this strongly autofluorescent, highly metabolically active perinuclear ring represents a subpopulation of mitochondria that are mobilized in response to the apoptotic stimulus and may provide the energy required to execute the final apoptotic steps. Thus, autofluorescence localization changes could serve as a sensitive, noninvasive indicator of early apoptosis in vivo. (c) 2006 Society of Photo-Optical Instrumentation Engineers. C1 Tufts Univ, Dept Biomed Engn, Medford, MA 02155 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Channing Lab,Dept Med, Boston, MA 02115 USA. Univ Hosp Herakleion, Dept Radiol, Iraklion 71110, Greece. Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Georgakoudi, I (reprint author), Tufts Univ, Dept Biomed Engn, 4 Colby St,Rm 153, Medford, MA 02155 USA. EM Irene.Georgakoudi@tufts.edu OI Munger, Karl/0000-0003-3288-9935 NR 43 TC 7 Z9 7 U1 0 U2 2 PU SPIE-INT SOCIETY OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD NOV-DEC PY 2006 VL 11 IS 6 AR 06029RR DI 10.1117/1.2401149 PG 10 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 132UU UT WOS:000243968700015 ER PT J AU Niedre, MJ Turner, GM Ntziachristos, V AF Niedre, Mark J. Turner, Gordon M. Ntziachristos, Vasilis TI Time-resolved imaging of optical coefficients through murine chest cavities SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE optical properties; diffusion theory; time; resolved measurements; femtosecond; in vivo ID DOMAIN PHOTON MIGRATION; BOUNDARY-CONDITIONS; BIOLOGICAL TISSUES; DIFFUSION EQUATION; TURBID MEDIA; STEADY-STATE; REFLECTANCE; TOMOGRAPHY; SPECTROSCOPY; SCATTERING AB As small animal optical imaging and tomography are gaining popularity for interrogating functional and molecular events in vivo, it becomes increasingly necessary to gain knowledge of the optical properties of the species investigated to better understand and describe photon propagation through their tissues. To achieve characterization of the spatial variation of average optical properties through murine chest cavities, time- and spatially resolved measurements of femto-second laser pulse transmission are performed through mice using a high-speed gated image intensifier. Application of time-resolved diffusion theory for finite slab geometry is first confirmed on phantoms and then applied to in vivo measurements for spatially resolving and quantifying mouse optical properties. Photon transmission images through mouse chest cavities are further obtained at different time gates to visualize the spatial variation observed and confirm the optical coefficient patterns calculated. (c) 2006 Society of Photo-Optical Instrumentation Engineers. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res,Lab Bioopt & Mol Imaging, Charlestown, MA 02129 USA. RP Niedre, MJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res,Lab Bioopt & Mol Imaging, Bldg 149,13th St Room 5406, Charlestown, MA 02129 USA. EM mniedre@partners.org; vasilis@helix.mgh.harvard.edu NR 24 TC 9 Z9 9 U1 0 U2 2 PU SPIE-INT SOCIETY OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD NOV-DEC PY 2006 VL 11 IS 6 AR 06118R DI 10.1117/1.2400702 PG 7 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 132UU UT WOS:000243968700020 ER PT J AU Salomatina, E Jiang, B Novak, J Yaroslavsky, AN AF Salomatina, Elena Jiang, Brian Novak, John Yaroslavsky, Anna N. TI Optical properties of normal and cancerous human skin in the visible and near-infrared spectral range SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE skin; cancer; scattering; absorption; integrating sphere spectrophotometry; inverse Monte Carlo technique ID MOHS MICROGRAPHIC SURGERY; POLARIZED-LIGHT; TISSUES; REFLECTANCE; EXCISIONS; TUMORS; BLOOD AB Differences in absorption and/or scattering of cancerous and normal skin have the potential to provide a basis for noninvasive cancer detection. In this study, we have determined and compared the in vitro optical properties of human epidermis, dermis, and subcutaneous fat with those of nonmelanoma skin cancers in the spectral range from 370 to 1600 nm. Fresh specimens of normal and cancerous human skin were obtained from surgeries. The samples were rinsed in saline solution and sectioned. Diffuse reflectance and total transmittance were measured using an integrating sphere spectrophotometer. Absorption and reduced scattering coefficients were calculated from the measured quantities using an inverse Monte Carlo technique. The differences between optical properties of each normal tissue-cancer pair were statistically analyzed. The results indicate that there are significant differences in the scattering of cancerous and healthy tissues in the spectral range from 1050 to 1400 nm. In this spectral region, the scattering of cancerous lesions is consistently lower than that of normal tissues, whereas absorption does not differ significantly, with the exception of nodular basal cell carcinomas (BCC). Nodular BCCs exhibit significantly lower absorption as compared to normal skin. Therefore, the spectral range between 1050 and 1400 nm appears to be optimal for nonmelanoma skin cancer detection. (c) 2006 Society of Photo-Optical Instrumentation Engineers. C1 Harvard Univ, Sch Med, Wellman Ctr Photomed, Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Shapiro Clin Ctr, Boston, MA 02134 USA. RP Yaroslavsky, AN (reprint author), Harvard Univ, Sch Med, Wellman Ctr Photomed, Massachusetts Gen Hosp, 55 Fruit St,BAR314B, Boston, MA 02114 USA. EM Yaroslav@helix.mgh.harvard.edu NR 32 TC 199 Z9 202 U1 3 U2 44 PU SPIE-INT SOCIETY OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 J9 J BIOMED OPT JI J. Biomed. Opt. PD NOV-DEC PY 2006 VL 11 IS 6 AR 064026 DI 10.1117/1.2398928 PG 9 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 132UU UT WOS:000243968700029 PM 17212549 ER PT J AU Jawa, A McCarty, P Doornberg, J Harris, M Ring, D AF Jawa, Andrew McCarty, Pearce Doornberg, Job Harris, Mitch Ring, David TI Extra-articular distal-third diaphyseal fractures of the humerus - A comparison of functional bracing and plate fixation SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID SHAFT FRACTURES; INTERNAL-FIXATION AB Background: There are strong advocates for both operative and nonoperative treatment of distal-third diaphyseal fractures of the humerus, but there are few comparative data. We performed a retrospective comparison of these two treatment methods. Methods: Fifty-one consecutive patients with a closed, extra-articular fracture of the distal one-third of the humeral diaphysis were identified from an orthopaedic trauma database. Forty patients were followed for at least six months or until healing of the fracture. Eleven patients were excluded because of inadequate follow-up. Nineteen patients had been managed with plate-and-screw fixation, and twenty-one had been managed with functional bracing. Results: Among the operatively treated patients, one had loss of fixation, one had a postoperative infection, and one required tendon transfers for the treatment of a preoperative radial nerve palsy that did not resolve. Three new postoperative radial nerve palsies developed, and one had not resolved when the patient was last evaluated, three months after surgery. All operatively treated fractures healed with <10 degrees of angular deformity, and one patient lost 200 of shoulder or elbow motion. Among the nonoperatively treated fractures, two were converted to plate fixation because of the treating surgeons' concern regarding alignment and radial nerve palsy. Only one patient had >30 degrees of malalignment in any plane. Two patients had development of skin breakdown during treatment and completed treatment in a sling. Two patients lost >= 20 degrees of elbow or shoulder motion. Conclusions: For extra-articular distal-third diaphyseal humeral fractures, operative treatment achieves more predictable alignment and potentially quicker return of function but risks iatrogenic nerve injury and infection and the need for reoperation. Functional bracing can be associated with skin problems and varying degrees of angular deformity, but function and range of motion are usually excellent. Level of Evidence: Therapeutic Level III. See Instructions to Authors for a complete description of levels of evidence. C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Yawkey Ctr, Boston, MA 02114 USA. Brigham & Womens Hosp, Dept Orthopaed Surg, Boston, MA 02115 USA. RP Jawa, A (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Yawkey Ctr, Suite 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org NR 13 TC 48 Z9 53 U1 1 U2 1 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD NOV PY 2006 VL 88A IS 11 BP 2343 EP 2347 DI 10.2106/JBJS.F.00334 PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 101VT UT WOS:000241769800004 PM 17079389 ER PT J AU Slover, J Espehaug, B Havelin, LI Engesaeter, LB Furnes, O Tomek, I Tosteson, A AF Slover, James Espehaug, Birgitte Havelin, Leif Ivar Engesaeter, Lars Birger Furnes, Ove Tomek, Ivan Tosteson, Anna TI Cost-effectiveness of unicompartmental and total knee arthroplasty in elderly low-demand patients - A Markov decision analysis SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID FOLLOW-UP EVALUATION; SURVIVORSHIP ANALYSIS; CLINICAL-EXPERIENCE; UNITED-STATES; REPLACEMENT; OUTCOMES; ARTHRITIS; REVISION; REGISTER; 8-YEAR AB Background: Interest in unicompartmental knee arthroplasty has recently increased in the United States, making a firm understanding of the indications for this procedure important. The purpose of this study was to examine the cost-effectiveness of unicompartmental knee arthroplasty compared with total knee arthroplasty in elderly low-demand patients. Methods: A Markov decision model was used to evaluate the cost-effectiveness of unicompartmental knee arthroplasty as compared with total knee arthroplasty in the elderly population. Transition probabilities were estimated from the Norwegian Arthroplasty Register and the arthroplasty literature, and costs were based on the average Medicare reimbursement for unicompartmental, tricompartmental, and revision knee arthroplasties. Outcomes were measured in quality-adjusted life-years. Results: Our model showed unicompartmental knee arthroplasty to be a cost-effective strategy for this population as long as the annual probability of revision is <4%. The cost of unicompartmental knee arthroplasty must be greater than $13,500 or the cost of total knee arthroplasty must be less than $8500 before total knee arthroplasty becomes more cost-effective. Conclusions: Our model suggests that, on the basis of currently available cost and outcomes data, unicompartmental knee arthroplasty and total knee arthroplasty have similar cost-effectiveness profiles in the elderly low-demand patient population. However, several important parameters that could alter the cost-effectiveness analysis were identified; these included implant survival rates, costs, perioperative mortality and infection rates, and utility values achieved with each procedure. The thresholds identified in this study may help decision-makers to evaluate the cost-effectiveness of each strategy as further research characterizes the variables associate with unicompartmental and total knee arthroplasties and may be helpful for designing future appropriate clinical trials. Level of Evidence: Economic and decision analysis, Level II. See Instructions to Authors for a complete description of levels of evidence. C1 Dartmouth Hitchcock Med Ctr, Dept Orthopaed Surg, Multidisciplinary Clin Res Ctr Musculoskeletal Di, Lebanon, NH 03756 USA. RP Slover, J (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg S456, 55 Fruit St, Boston, MA 02114 USA. EM jslover@partners.org FU NIAMS NIH HHS [P60-AR48094] NR 39 TC 49 Z9 49 U1 1 U2 2 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD NOV PY 2006 VL 88A IS 11 BP 2348 EP 2355 DI 10.2106/JBJS.E.01033 PG 8 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 101VT UT WOS:000241769800005 PM 17079390 ER PT J AU Malchano, ZJ Neuzil, P Cury, RC Holmvang, G Weichet, J Schmidt, EJ Ruskin, JN Reddy, VY AF Malchano, Zachary J. Neuzil, Petr Cury, Ricardo C. Holmvang, Godtfred Weichet, Jiri Schmidt, Ehud J. Ruskin, Jeremy N. Reddy, Vivek Y. TI Integration of cardiac CT/MR imaging with three-dimensional electroanatomical mapping to guide catheter manipulation in the left atrium: Implications for catheter ablation of atrial fibrillation SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Article DE catheter ablation; atrial fibrillation; image integration; MRI; CT ID PULMONARY VEIN AB Introduction: Preprocedural cardiac imaging (CT/MRI) and intraprocedural electroanatomical mapping (EAM) are commonly used during left atrial (LA) catheter ablation of atrial fibrillation (AF). In the optimal scenario, the imaging datasets would be directly integrated with the EAM system to guide catheter mapping based on the accurate individual cardiac anatomy. Methods and Results: Strategies to align the EAM and imaging data were assessed by simulations using a life-size model of the LA and aorta. This revealed that the optimal strategy includes mapping both the aorta and LA. Respiratory changes in cardiac anatomy were evaluated by MR angiography performed in 10 patients during both inspiration and expiration. Comparison of paired images revealed inferior and anterior movement of the LA relative to the aorta with inspiration. Next, image integration was employed in a series of patients (n = 13) scheduled for AF catheter ablation. After preprocedural CT angiography (7 during inspiration and 6 during expiration), three-dimensional anatomical renderings of these images were integrated with the EAM data in a custom workstation to permit real-time catheter manipulation within these constructs. The electrophysiologist was blinded to these integrated images, but the accuracy of the process was assessed real-time by a second operator. This revealed poor alignment during inspiration but good alignment during expiration-the respiratory phase most closely resembling that during EAM. Conclusions: This study supports the feasibility of integrating preacquired cardiac images with real-time electroanatomical mapping to guide catheter movement in the LA in a reliable and clinically relevant manner. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac MRI Unit, Boston, MA 02114 USA. Na Homolce Hosp, Cardiac Arrhythmia Serv, Prague, Czech Republic. GE Med Syst, Waukesha, WI USA. RP Reddy, VY (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Arrhythmia Serv, 55 Fruit St,Gray Bigelow 109, Boston, MA 02114 USA. EM vreddy@partners.org FU NHLBI NIH HHS [K23 HL68064-02] NR 10 TC 77 Z9 79 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1045-3873 J9 J CARDIOVASC ELECTR JI J. Cardiovasc. Electrophysiol. PD NOV PY 2006 VL 17 IS 11 BP 1221 EP 1229 DI 10.1111/j.1540-8167.2006.00616.x PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 096HK UT WOS:000241368000014 PM 17074008 ER PT J AU He, L Game, BA Nareika, A Garvey, WT Huang, Y AF He, Lin Game, Bryan A. Nareika, Alena Garvey, W. Timothy Huang, Yan TI Administration of pioglitazone in low-density lipoprotein receptor-deficient mice inhibits lesion progression and matrix metalloproteinase expression in advanced atherosclerotic plaques SO JOURNAL OF CARDIOVASCULAR PHARMACOLOGY LA English DT Article DE matrix metalloproteinase; atherosclerosis; diabetes; gene expression ID MUSCLE-CELL-MIGRATION; COLLAGENASE-1 GENE-TRANSCRIPTION; RAT CAROTID-ARTERY; ACTIVATOR PROTEIN-1; BALLOON INJURY; OVEREXPRESSION; ASSOCIATION; MEMBRANE; INSULIN; DISEASE AB Recent clinical trials have provided evidence that pioglitazone reduces cardiovascular events in patients with type 2 diabetes. However, the underlying mechanisms are not well understood. Because it has been well established that disruption of atherosclerotic plaques is a key event involved in acute myocardial infarction, we hypothesized that pioglitazone reduces cardiovascular events by stabilizing atherosclerotic lesions. In this study, we used an animal model to test our hypothesis. Low-density lipoprotein receptor-deficient (LDLR-/-) male mice were first fed a high-fat diet for 4 months to induce the formation of aortic atherosclerotic plaques and then treated with pioglitazone for the next 3 months. Analysis of atherosclerotic plaques at the end of the study showed that treatment with pioglitazone at 20 mg/kg/day reduced the progression of atherosclerotic plaques as compared to untreated mice. Furthermore, gene array analysis, quantitative real-time polymerase chain reaction, and immunohistochemical analysis showed that pioglitazone inhibited high-fat diet-induced upregulation of matrix metalloprotemase (MMP) expression. Finally, Sirius red staining showed that atherosclerotic lesions in mice receiving pioglitazone had higher collagen contents than those in untreated mice. This study demonstrated for the first time that administration of pioglitazone in LDLR-/- mice inhibited lesion progression and MMP expression in established atherosclerotic plaques and thus delineated a potential mechanism by which pioglitazone reduces cardiovascular events in patients with type 2 diabetes. C1 Med Univ S Carolina, Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29403 USA. Med Univ S Carolina, Div Endocrinol Diabet & Med Genet, Charleston, SC 29403 USA. Univ Alabama, Dept Nutr Sci, Birmingham, AL 35294 USA. Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. Med Univ S Carolina, Dept Med, Charleston, SC 29403 USA. RP Huang, Y (reprint author), Med Univ S Carolina, Ralph H Johnson Vet Affairs Med Ctr, 114 Doughty St,Room 531, Charleston, SC 29403 USA. EM huangyan@musc.edu NR 36 TC 13 Z9 15 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0160-2446 J9 J CARDIOVASC PHARM JI J. Cardiovasc. Pharmacol. PD NOV PY 2006 VL 48 IS 5 BP 212 EP 222 DI 10.1097/01.fjc.0000248831.21973.c4 PG 11 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA 110DP UT WOS:000242358800004 PM 17110803 ER PT J AU Elango, N Li, Y Shivshankar, P Katz, MS AF Elango, Narayanasamy Li, Ye Shivshankar, Pooja Katz, Michael S. TI Expression of RUNX2 isoforms: Involvement of cap-dependent and cap-independent mechanisms of translation SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE type-I RUNX2; type-II RUNX2; internal ribosomal entry site; cap-dependent translation; 4E-BP1; RNA Aptamer-1 ID RIBOSOME ENTRY SITES; BONE MORPHOGENETIC PROTEIN-2; OSTEOBLAST DIFFERENTIATION; CLEIDOCRANIAL DYSPLASIA; TRANSCRIPTION FACTOR; GENE-EXPRESSION; CHONDROCYTE MATURATION; DOMAIN PROTEINS; RNA; CBFA1 AB RUNX2, a major regulator of skeletogenesis, is expressed as type-I and type-II isoforms. Whereas most eukaryotic mRNAs are translated by the cap-dependent scanning mechanism, translation of many mRNAs including type-I and type-II RUNX2 mRNAs has been reported to be initiated by a cap independent internal ribosomal entry site (IRES). Since the dicistronic plasmid assay used to demonstrate IRES has been questioned, we investigated the presence of IRES in RUNX2 mRNAs using dicistronic plasmid and mRNA assays. Our results show that the dicistronic plasmid assay cannot be used to demonstrate IRES in RUNX2 mRNAs because the intercistronic region of dicistronic plasmids containing the 5'-UTRs of both RUNX2 mRNAs operates as a cryptic promoter. In dicistronic mRNA transfection studies the 5'-UTRs of both RUNX2 mRNAs exhibited no IRES activity. When transfected into osteoblastic cells, monocistronic reporter mRNA preceded by the 5'-UTR of type-II RUNX2 (Type-II-FLuc-A100) was translated to a high degree only in the presence of a functional cap (m(7) GpppG); in contrast, luciferase mRNA preceded by the 5'-UTR of type-I-RUNX2 mRNA (Type-1-FLuc-A100) was translated poorly in the presence of either m(7) GpppG or a nonfunctional cap (ApppG). Notably, in transfected cells inhibitors of cap-dependent translation suppressed the translation of m(7) GpppG-capped Type-II-FLuc-A100, but not ApppG-capped reporter mRNA preceded by the IRES-containing hepatitis C virus (HCV) 5'-UTR. Our study demonstrates that type-II RUNX2 mRNA is translated by the cap-dependent mechanism. Although efficient translation of type-I RUNX2 mRNA appears to require a process other than cap-dependent, the mechanism of type-I RUNX2 mRNA translation remains to be resolved. C1 S Texas Vet Hlth Care Syst, Geriatr Res,Educ & Clin Ctr, Audie L Murphy Div, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Dept Med, Div Geriatr & Gerontol, San Antonio, TX 78284 USA. RP Elango, N (reprint author), VA Med Ctr, GRECC 182, 7400 Merton Minter Blvd, San Antonio, TX 78229 USA. EM elangon@uthscsa.edu NR 52 TC 10 Z9 10 U1 0 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD NOV 1 PY 2006 VL 99 IS 4 BP 1108 EP 1121 DI 10.1002/jcb.20909 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 100SO UT WOS:000241689200011 PM 16767703 ER PT J AU Ross, DS AF Ross, Douglas S. TI Predicting thyroid malignancy SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Editorial Material ID NEEDLE-ASPIRATION-CYTOLOGY; NODULAR GOITER; CANCER; PREVALENCE; SOLITARY; RISK C1 Massachusetts Gen Hosp, Thyroid Unit ACC730S, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Ross, DS (reprint author), Massachusetts Gen Hosp, Thyroid Unit ACC730S, Boston, MA 02114 USA. EM dross@partners.org NR 16 TC 23 Z9 24 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD NOV PY 2006 VL 91 IS 11 BP 4253 EP 4255 DI 10.1210/jc.2006-1772 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 102MO UT WOS:000241816300010 PM 17088441 ER PT J AU Welt, CK Arason, G Gudmundsson, JA Adams, J Palsdottir, H Gudlaugsdottir, G Ingadottir, G Crowley, WF AF Welt, C. K. Arason, G. Gudmundsson, J. A. Adams, J. Palsdottir, H. Gudlaugsdottir, G. Ingadottir, G. Crowley, W. F. TI Defining constant versus variable phenotypic features of women with polycystic ovary syndrome using different ethnic groups and populations SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID GONADOTROPIN-RELEASING-HORMONE; BETA-CELL FUNCTION; METABOLIC SYNDROME; INSULIN-RESISTANCE; HYPERANDROGENIC WOMEN; ANDROGEN EXCESS; SYNDROME PCOS; PREVALENCE; GLUCOSE; ENDOCRINE AB Context: The phenotype of women with polycystic ovary syndrome (PCOS) is variable, depending on the ethnic background. Objective: The phenotypes of women with PCOS in Iceland and Boston were compared. Design: The study was observational with a parallel design. Setting: Subjects were studied in an outpatient setting. Patients: Women, aged 18-45 yr, with PCOS defined by hyperandrogenism and fewer than nine menses per year, were examined in Iceland (n = 105) and Boston (n = 262). Intervention: PCOS subjects underwent a physical exam, fasting blood samples for androgens, gonadotropins, metabolic parameters, and a transvaginal ultrasound. Main Outcome Measures: The phenotype of women with PCOS was compared between Caucasian women in Iceland and Boston and among Caucasian, African-American, Hispanic, and Asian women in Boston. Results: Androstenedione (4.0 +/- 1.3 vs. 3.5 +/- 1.2 ng/ml; P < 0.01) was higher and testosterone (54.0 +/- 25.7 vs. 66.2 +/- 35.6 ng/dl; P < 0.01), LH (23.1 +/- 15.8 vs. 27.6 +/- 16.2 IU/liter; P < 0.05), and Ferriman Gallwey score were lower (7.1 +/- 6.0 vs. 15.4 +/- 8.5; P < 0.001) in Caucasian Icelandic compared with Boston women with PCOS. There were no differences in fasting blood glucose, insulin, or homeostasis model assessment in body mass index-matched Caucasian subjects from Iceland or Boston or in different ethnic groups in Boston. Polycystic ovary morphology was demonstrated in 93-100% of women with PCOS in all ethnic groups. Conclusions: The data demonstrate differences in the reproductive features of PCOS without differences in glucose and insulin in body mass index-matched populations. These studies also suggest that measuring androstenedione is important for the documentation of hyperandrogenism in Icelandic women. Finally, polycystic ovary morphology by ultrasound is an almost universal finding in women with PCOS as defined by hyperandrogenism and irregular menses. C1 Massachusetts Gen Hosp, Reprod Endocrine Unit, Dept Med, Boston, MA 02114 USA. Pjonustumiiostoo Rannsoknaverkefna, IS-105 Reykjavik, Iceland. Univ Iceland, Landspitali Hosp, Dept Obstet & Gynecol, IS-101 Reykjavik, Iceland. RP Welt, CK (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, Dept Med, 55 Fruit St,BHX 511, Boston, MA 02114 USA. EM cwelt@partners.org OI Welt, Corrine/0000-0002-8219-5504 FU NCRR NIH HHS [M01-RR-01066]; NICHD NIH HHS [U01 HD417] NR 42 TC 70 Z9 70 U1 2 U2 6 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD NOV PY 2006 VL 91 IS 11 BP 4361 EP 4368 DI 10.1210/jc.2006-1191 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 102MO UT WOS:000241816300026 PM 16940441 ER PT J AU Page, ST Amory, JK Anawalt, BD Irwig, MS Brockenbrough, AT Matsumoto, AM Bremner, WJ AF Page, Stephanie T. Amory, John K. Anawalt, Bradley D. Irwig, Michael S. Brockenbrough, Andrew T. Matsumoto, Alvin M. Bremner, William J. TI Testosterone gel combined with depomedroxyprogesterone acetate is an effective male hormonal contraceptive regimen and is not enhanced by the addition of a GnRH antagonist SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID INSULIN-LIKE FACTOR-3; NORMALIZES ANDROGEN LEVELS; NORMAL YOUNG MEN; MEDROXYPROGESTERONE ACETATE; TRANSDERMAL TESTOSTERONE; HYPOGONADAL MEN; CLINICAL-TRIAL; LEVONORGESTREL IMPLANTS; INJECTABLE TESTOSTERONE; ORAL LEVONORGESTREL AB Introduction: Exogenous androgens plus progestins can be used to suppress spermatogenesis, resulting in effective male hormonal contraception; however, induction of azoospermia can require 3-6 months, and these methods require injectable or implantable androgens. We hypothesized that testosterone (T) transdermal gel (T gel) could be combined with a depot formulation of the progestin, depomedroxyprogesterone acetate (DMPA), with or without the potent GnRH antagonist, acyline, to suppress spermatogenesis conveniently, rapidly, and reversibly. Objectives: The objectives of the study were: 1) to determine the rate of severe oligospermia (<= 1 million sperm/ml) using T gel + DMPA; and 2) to determine whether the addition of acyline to T gel + DMPA during the first 12 wk of the regimen would accelerate and improve suppression of spermatogenesis. Methods: Forty-four healthy men, ages 18-55 yr, were randomized to T gel (100 mg daily) + DMPA (300 mg/3 months) or acyline (300 mu g/kg center dot 2 wk x 12 wk) + T gel + DMPA. Thirty-eight men completed the 24-wk treatment protocol. Results: All men had dramatic suppression of spermatogenesis; 90% of the subjects became severely oligospermic, a rate comparable to implantable and injectable T + progestin combinations. The addition of acyline did not significantly accelerate spermatogenic suppression or improve rates of severe oligospermia. There were no serious adverse events, and there were minimal changes in weight, serum lipids, and prostate-specific antigen. Conclusions: The combination of T gel + DMPA is a promising new regimen in male contraception. The addition of the GnRH antagonist acyline, as part of an induction phase in a male contraception regimen, has limited clinical utility. Additional studies using T gel for male contraception are warranted. C1 Univ Washington, Dept Med, Seattle, WA 98195 USA. Vet Affairs Puget Sound Hlth Care Syst, Geriatr Res Educ & Clin Ctr, Seattle, WA 98108 USA. Vet Affairs Puget Sound Hlth Care Syst, Dept Med, Seattle, WA 98108 USA. RP Page, ST (reprint author), POB 357138,1959 NE Pacific, Seattle, WA 98195 USA. EM page@u.washington.edu OI Irwig, Michael/0000-0003-1231-1941 FU NIA NIH HHS [K23 AG027238, K23 AG027238-02]; NICHD NIH HHS [U54 HD-42454, U54-HD-12629] NR 38 TC 37 Z9 37 U1 0 U2 8 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD NOV PY 2006 VL 91 IS 11 BP 4374 EP 4380 DI 10.1210/jc.2006-1411 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 102MO UT WOS:000241816300028 PM 16940442 ER PT J AU Hadigan, C Liebau, J Torriani, M Andersen, R Grinspoon, S AF Hadigan, Colleen Liebau, James Torriani, Martin Andersen, Rebecca Grinspoon, Steven TI Improved triglycerides and insulin sensitivity with 3 months of acipimox in human immunodeficiency virus-infected patients with hypertriglyceridemia SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID FREE FATTY-ACIDS; INTRAMYOCELLULAR LIPID-ACCUMULATION; ACTIVE ANTIRETROVIRAL THERAPY; DIABETES-MELLITUS; HIV-LIPODYSTROPHY; ADIPOSE-TISSUE; DISEASE RISK; LIPOLYSIS; REDISTRIBUTION; DYSLIPIDEMIA AB Context: Metabolic abnormalities such as hypertriglyceridemia remain a challenge for optimizing long-term health in HIV- infected patients. Objective: Elevation of free fatty acids ( FFAs) may contribute to hyperlipidemia and insulin resistance in HIV. We evaluated the efficacy and safety of chronic inhibition of lipolysis in HIV- infected men and women with hypertrigyceridemia. We hypothesized that acipimox would lead to significant reductions in triglycerides and improved insulin sensitivity, compared with placebo. Design: A 3- month, randomized, double- blind, controlled trial of acipimox ( 250 mg thrice daily) vs. placebo was conducted in 23 HIV-infected men and women with hypertriglyceridemia ( > 150 mg/ dl), abnormal fat distribution, and no current lipid-lowering therapy. The primary outcome variable was triglyceride concentration, and insulin sensitivity measured by hyperinsulinemic euglycemic clamp was a secondary outcome. Setting: The study was conducted at an academic medical center. Results: Acipimox resulted in significant reductions in FFAs [ mean change -0.38 (0.06) vs. 0.08 ( 0.06) mEq/ liter with placebo, -68 vs. + 17% change from mean baseline, P < 0.0001], decreased rates of lipolysis ( P < 0.0001), and a median triglyceride decrease from 238 mg/ dl at baseline to 190 mg/ dl, compared with an increase from 290 to 348 mg/ dl in the placebo group ( P < 0.01). Acipimox improved insulin sensitivity [ acipimox + 2.31 ( 0.74) vs. placebo - 0.21 ( 0.90) mg glucose per kilogram lean body mass per minute, or + 31 vs. - 2% change from mean baseline values, P = 0.04]. Improvements in insulin sensitivity were significantly correlated with reductions in FFAs ( r = -0.62, P = 0.003) and lipolysis ( r = -0.59, P = 0.005). Conclusions: Acipimox resulted in significant sustained reductions in lipolysis, improved glucose homeostasis, and significant but modest reductions in triglycerides in HIV- infected individuals with abnormal fat distribution and hypertriglyceridemia. Improvement in overall metabolic profile with acipimox suggests a potential clinical utility for this agent that requires further investigation. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Program Nutr Metab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Musculoskeletal Radiol, Boston, MA 02114 USA. RP Hadigan, C (reprint author), NIAID, NIH, 10 Ctr Dr,Bldg 10,Room 11C103, Bethesda, MD 20892 USA. EM hadiganc@niaid.nih.gov FU NCRR NIH HHS [K23 RR018715, K23-RR-18715, M01 RR001066, M01-RR-01066]; NHLBI NIH HHS [R21-HL73675, R21 HL073675]; NIDDK NIH HHS [P30 DK040561-11, P30 DK040561, K23-DK-02844, R01-DK-59535, K23 DK002844, R01 DK059535] NR 42 TC 23 Z9 24 U1 0 U2 4 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD NOV PY 2006 VL 91 IS 11 BP 4438 EP 4444 DI 10.1210/jc.2006-1174 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 102MO UT WOS:000241816300037 PM 16940448 ER PT J AU Batista, DL Zhang, X Gejman, R Ansell, PJ Zhou, YL Johnson, SA Swearingen, B Hedley-Whyte, ET Stratakis, CA Klibanski, A AF Batista, Dalia L. Zhang, Xun Gejman, Roger Ansell, Peter J. Zhou, Yunli Johnson, Sarah A. Swearingen, Brooke Hedley-Whyte, E. Tessa Stratakis, Constantine A. Klibanski, Anne TI The effects of SOM230 on cell proliferation and adrenocorticotropin secretion in human corticotroph pituitary adenomas SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID SOMATOSTATIN RECEPTOR SUBTYPES; CUSHINGS-SYNDROME; MEDICAL THERAPY; ANALOG SOM230; IN-VITRO; DISEASE; EXPRESSION; TUMORS; MANAGEMENT; MACROADENOMAS AB Context: There is no tumor-directed medical therapy available for Cushing's disease. Objective: The objective was to determine the in vitro effect of the somatostatin analog pasireotide (SOM230) on cell proliferation in human corticotroph tumors. Design/Methods: Expression of somatostatin receptors (SSTR 1-5) was determined by quantitative RT-PCR in 13 human corticotroph tumors and by immunohistochemistry (IHC) in 12 of the 13 tumors. SOM230 effects on cell proliferation and ACTH release were evaluated in vitro using primary cultures of six of the 13 human corticotroph adenomas. Results: In our series, we found expression of SSTR subtypes 1, 2, 4, and 5 in human corticotroph tumors by quantitative RT-PCR. All receptor subtypes were detected by IHC, with SSTR subtype 5 having the highest IHC score in 83% (10 of 12) of the cases. Significant suppression of cell proliferation was observed in all tumors cultured (percent suppression range: 10-70%; P = 0.045-0.001). SOM230 inhibited ACTH secretion in five of the six tumors cultured (percent suppression range: 23-56%; P = 0.042-0.001). Conclusion: Corticotroph tumors express multiple SSTR subtypes. SOM230 significantly suppressed cell proliferation and ACTH secretion in primary cultures of human corticotroph tumors. These in vitro results support the hypothesis that SOM230 may have a role in the medical therapy of corticotroph tumors. C1 Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Neuropathol Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Neurosurg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. NICHHD, Sect Endocrinol & Genet, NIH, Bethesda, MD 02892 USA. NICHHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Klibanski, A (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, 55 Fruit St,BUL457, Boston, MA 02114 USA. EM aklibanski@partners.org OI Tersey, Sarah/0000-0003-0667-2361 FU Intramural NIH HHS NR 39 TC 122 Z9 128 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD NOV PY 2006 VL 91 IS 11 BP 4482 EP 4488 DI 10.1210/jc.2006-1245 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 102MO UT WOS:000241816300044 PM 16940446 ER PT J AU McGinnis, KA Fultz, SL Skanderson, M Conigliaro, J Bryant, K Justice, AC AF McGinnis, Kathleen A. Fultz, Shawn L. Skanderson, Melissa Conigliaro, Joseph Bryant, Kendall Justice, Amy C. TI Hepatocellular carcinoma and non-Hodgkin's lymphoma: The roles of HIV, hepatitis C infection, and alcohol abuse SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 15th International AIDS Conference CY JUL 11-17, 2004 CL Bangkok, THAILAND ID VIRUS-INFECTION; UNITED-STATES; CONNECTICUT WOMEN; AIDS; COHORT; VETERANS; RISK; PREVALENCE; SCHIZOPHRENIA; ASSOCIATION AB Purpose To explore the relationship of HIV, hepatitis C (HCV), and alcohol abuse/dependence to risk for hepatocellular carcinoma and non-Hodgkin's lymphoma (NHL). Patients and Methods Male veterans ( n = 14,018) with a first HIV diagnosis in the Veterans Affairs Healthcare System from October 1997 to September 2004; and 28,036 age-, race-, sex-, and location-matched HIV-negative veterans were identified. We examined the incidence of hepatocellular carcinoma and NHL and presence of HCV and alcohol abuse/dependence using International Classification of Diseases, ninth revision (ICD-9-CM) codes. HIV-positive to HIV-negative incident rate ratios (IRRs) and 95% CIs for the occurrence of hepatocellular carcinoma and NHL were calculated using Poisson regression models. Results HIV-positive veterans were at greater risk for hepatocellular carcinoma than HIV-negative veterans (IRR = 1.68; 95% CI, 1.02 to 2.77). After adjusting for HCV infection and alcohol abuse/ dependence, HIV status was not independently associated with hepatocellular cancer ( IRR = 0.96; 95% CI, 0.56 to 1.63). HIV-positive veterans had 9.71 times ( 95% CI, 6.99 to 13.49) greater risk of NHL than HIV-negative veterans. After adjusting for HCV and alcohol abuse/ dependence, the IRR for NHL comparing HIV-positive with HIV-negative veterans is similar ( IRR = 10.03, 95% CI, 7.19 to 13.97). Conclusion HIV-positive veterans have a higher relative incidence of hepatocellular carcinoma and NHL than HIV-negative veterans. For hepatocellular carcinoma, this association appears to be largely explained by the higher prevalence of HCV and alcohol abuse/ dependence. Efforts to decrease hepatocellular carcinoma among persons with HIV should focus primarily on detecting and treating HCV and reducing heavy alcohol use. C1 Yale Univ, Sch Med, Dept Med, West Haven, CT 06516 USA. Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA USA. Univ Pittsburgh, Univ Ctr Social & Urban Res, Pittsburgh, PA USA. VA Connecticut Healthcare Syst, West Haven, CT USA. Univ Kentucky, Lexington, KY USA. NIAAA, NIH, Bethesda, MD USA. RP Justice, AC (reprint author), Yale Univ, Sch Med, Dept Med, 950 Campbell Ave, West Haven, CT 06516 USA. EM amy.justice2@va.gov FU PHS HHS [U01-13566] NR 31 TC 41 Z9 41 U1 1 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV 1 PY 2006 VL 24 IS 31 BP 5005 EP 5009 DI 10.1200/JCO.2006.05.7984 PG 5 WC Oncology SC Oncology GA 102PX UT WOS:000241825900011 PM 17075119 ER EF