FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Hatjiharissi, E Mitsiades, CS Bryan, CT Lian, X Yang, C Adamia, S Leleu, X Roccaro, A Loakimidis, L Hunter, ZR Patterson, CJ Ghobrial, I Treon, SP AF Hatjiharissi, Evdoxia Mitsiades, Constantine S. Bryan, Ciccarelli T. Lian, Xu Yang, Cao Adamia, Sophia Leleu, Xavier Roccaro, Aldo Loakimidis, Leukothea Hunter, Zachary R. Patterson, Christopher J. Ghobrial, Irene Treon, Steven P. TI Comprehensive molecular characterization of malignant and microenvironmental cells in Waldenstrom's macroglobulinemia by gene expression profiling SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 Dana Farber Canc Inst, Bing Ctr Walderstrom Macroglobulinemia, Boston, MA 02115 USA. [Mitsiades, Constantine S.] Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. [Hatjiharissi, Evdoxia; Mitsiades, Constantine S.; Adamia, Sophia; Leleu, Xavier; Roccaro, Aldo; Ghobrial, Irene; Treon, Steven P.] Harvard Med Sch, Boston, MA 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 2007 VL 110 IS 11 MA 3174 BP 933A EP 933A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100804211 ER PT J AU Li, ZJ Lu, J Sun, M Mi, SL Zhang, H Luo, RT Qian, ZJ Neilly, MB Wang, YG Jin, J Zhang, YM Bohlander, SK Larson, R LeBeau, M Thirman, MJ Golub, TR Rowley, JD Chen, JJ AF Li, Zejuan Lu, Jun Sun, Miao Mi, Shuangli Zhang, Hao Luo, Roger T. Qian, Zhijian Neilly, Mary Beth Wang, Yungui Jin, Jie Zhang, Yanming Bohlander, Stefan K. Larson, Richard LeBeau, Michelle Thirman, Michael J. Golub, Todd R. Rowley, Janet D. Chen, Jianjun TI MicroRNA expression profiles in acute myeloid leukemia with common translocations SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Li, Zejuan; Sun, Miao; Mi, Shuangli; Luo, Roger T.; Qian, Zhijian; Neilly, Mary Beth; Zhang, Yanming; Larson, Richard; LeBeau, Michelle; Thirman, Michael J.; Rowley, Janet D.; Chen, Jianjun] Univ Chicago, Dept Med, Chicago, IL 60637 USA. [Lu, Jun; Zhang, Hao; Golub, Todd R.] MIT, Broad Inst, Cambridge, MA 02139 USA. [Lu, Jun; Golub, Todd R.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Howard Hughes Med Inst, Harvard Med Sch, Boston, MA 02115 USA. [Wang, Yungui; Jin, Jie] Zhejiang Univ, Inst Hematol, Dept Hematol, Hangzhou 310027, Peoples R China. [Bohlander, Stefan K.] Univ Munich, Hosp Grosshadern, Dept Med 3, Munich, Germany. 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 2007 VL 110 IS 11 MA 3181 BP 934A EP 935A PN 1 PG 2 WC Hematology SC Hematology GA 233OS UT WOS:000251100804218 ER PT J AU Zhou, J Zhong, R Corringham, S Sapp, T Soiffer, R Mitrovich, RC Lowy, I Bashey, A Ball, FD AF Zhou, Jiehua Zhong, Ruikun Corringham, Sue Sapp, Teresa Soiffer, Robert Mitrovich, Rachel C. Lowy, Izzy Bashey, Asad Ball, Fdward D. TI Flow cytometry analysis of peripheral blood CD4+/CD25+/FOXP3+T regulator cells from 11 patients treated with ipilimumab following relapse of malignancy after allogeneic hematopoietic stem cell transplantation SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Zhou, Jiehua; Zhong, Ruikun; Corringham, Sue; Ball, Fdward D.] Univ Calif San Diego, La Jolla, CA 92093 USA. [Sapp, Teresa; Bashey, Asad] Blood & Marrow Transplant & Leukemia, Atlanta, GA USA. [Soiffer, Robert] Dana Farber Canc Inst, Boston, MA USA. [Lowy, Izzy] Medarex Inc, Princeton, NJ 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 2007 VL 110 IS 11 MA 3240 BP 952A EP 952A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100804277 ER PT J AU Andreola, G Chittenden, M Shaffer, J Cosimi, AB Kawai, T Cotter, P Dey, BR Tolkoff-Rubin, N Preffer, F Saidman, S Kattleman, K Spitzer, TR Sachs, DH Sykes, M AF Andreola, Giovanna Chittenden, Meredith Shaffer, Juanita Cosimi, A. Benedict Kawai, Tatsuo Cotter, Pete Dey, Bimalangsho R. Tolkoff-Rubin, Nina Preffer, Frederic Saidman, Susan Kattleman, Kristin Spitzer, Thomas R. Sachs, David H. Sykes, Megan TI A role for regulatory cells in tolerance induction in recipients of haploidentical combined non-myeloablative bone marrow and kidney transplantation? SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Preffer, Frederic] Massachusetts Gen Hosp, Harvard Med Sch, 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 2007 VL 110 IS 11 MA 3255 BP 956A EP 956A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100804292 ER PT J AU Krause, DS Stowell, CP AF Krause, Daniela S. Stowell, Christopher P. TI Soluble CD44 is increased in haematopoietic stem cell grafts of patients with acute myeloid leukemia, multiple myeloma and non-hodgkin's lymphoma SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Krause, Daniela S.; Stowell, Christopher P.] 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 2007 VL 110 IS 11 MA 3286 BP 965A EP 965A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100804323 ER PT J AU Van Bennekom, CM Abel, GA Stone, RM Anderson, KC Raje, N Kaufman, DW AF Van Bennekom, Carla M. Abel, Gregory A. Stone, Richard M. Anderson, Kenneth C. Raje, Noopur Kaufman, David W. TI Attitudes toward participation in research, new treatments, and medication side effects among multiple myeloma and myelodysplastie syndrome patients - The patient registries at slone: Myeloma & MDS SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Van Bennekom, Carla M.; Kaufman, David W.] Boston Univ, Sloan Epidemiol Ctr, Boston, MA 02215 USA. [Abel, Gregory A.; Stone, Richard M.; Anderson, Kenneth C.] Dana Farber Canc Inst, Boston, MA USA. [Raje, Noopur] 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 2007 VL 110 IS 11 MA 3325 BP 976A EP 976A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100804362 ER PT J AU Shankaran, V Mckoy, J Djulbegovic, B Lyons, A Carson, K Tigue, C Dandade, N Tallman, M Sartor, O Bennet, C AF Shankaran, Veena Mckoy, June Djulbegovic, Ben Lyons, Allison Carson, Ken Tigue, Cara Dandade, Neal Tallman, Martin Sartor, Oliver Bennet, Charles TI Waiting for godot: Thirty-six month follow-up on accelerated FDA approval of drugs to treat hematologic malignancies SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Shankaran, Veena; Mckoy, June; Lyons, Allison; Carson, Ken; Tigue, Cara; Dandade, Neal; Tallman, Martin; Bennet, Charles] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Djulbegovic, Ben] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Sartor, Oliver] Dana Farber Canc Inst, Boston, MA 02115 USA. RI Djulbegovic, Benjamin/I-3661-2012 OI Djulbegovic, Benjamin/0000-0003-0671-1447 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 2007 VL 110 IS 11 MA 3340 BP 980A EP 981A PN 1 PG 2 WC Hematology SC Hematology GA 233OS UT WOS:000251100804377 ER PT J AU Wang, Y Krivtsov, A Losyev, G Armstrong, SA AF Wang, Yingzi Krivtsov, Andrei Losyev, Grigoriy Armstrong, Scott A. TI Hoxa9+Meis1a efficiently transform hematopoietic stem cells but not committed progenitors SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Wang, Yingzi; Krivtsov, Andrei; Losyev, Grigoriy; Armstrong, Scott A.] Childrens Hosp, Div Hematol Oncol, Boston, MA USA. [Armstrong, Scott A.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA USA. [Armstrong, Scott A.] Harvard Univ, Sch Med, Boston, MA 02115 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 2007 VL 110 IS 11 MA 3375 BP 989A EP 989A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100804412 ER PT J AU Kahl, BS Williams, ME Hong, F Gascoyne, R Horning, SJ AF Kahl, Brad S. Williams, Michael E. Hong, Fangxin Gascoyne, Randy Horning, Sandra J. TI Preliminary pharmacokinetic (PK) analysis of eastern cooperative oncology group protocol E4402: Rituximab extended schedule or re-treatment trial (RESORT) SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Kahl, Brad S.] Univ Wisconsin, Madison, WI USA. [Williams, Michael E.] Univ Virginia, Charlottesville, VA USA. [Hong, Fangxin] Dana Farber Canc Inst, Boston, MA 02115 USA. [Gascoyne, Randy] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. [Horning, Sandra J.] Stanford Univ, Palo Alto, CA 94304 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 2007 VL 110 IS 11 MA 3420 BP 1002A EP 1002A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100804457 ER PT J AU Hoghberg, EP Hammerman, P Takvorian, T Toomey, C Michaelson, J Rahemtullah, A Abramson, JS AF Hoghberg, Ephraim P. Hammerman, Peter Takvorian, Tak Toomey, Christiana Michaelson, James Rahemtullah, Aliyah Abramson, Jeremy S. TI Intermediate dose intravenous methotrexate (MTX) dramatically reduces the risk of secondary central nervous system (CNS) lymphoma SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Hoghberg, Ephraim P.; Takvorian, Tak; Abramson, Jeremy S.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Hammerman, Peter] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Michaelson, James; Rahemtullah, Aliyah] Massachusetts Gen Hosp, Dept Pathol, 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 2007 VL 110 IS 11 MA 3442 BP 1009A EP 1009A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100804479 ER PT J AU Foss, F Sjak-Shie, N Goy, A Jacobsen, E Advani, R Smith, M Komrokji, R Pendergrass, K Bolejack, V Watts, K Acosta, M AF Foss, Francine Sjak-Shie, Nelida Goy, Andre Jacobsen, Eric Advani, Ranjana Smith, Mitchell Komrokji, Rami Pendergrass, Kelly Bolejack, Vanessa Watts, Karen Acosta, Mark TI Denileukin diftitox (ONTAK) plus CHOP chemotherapy in patients with peripheral T-Cell lymphomas (PTCL), the CONCEPT trial SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Foss, Francine] Yale Med Sch, Yale Canc Ctr, New Haven, CT USA. [Sjak-Shie, Nelida] US Oncol, St Louis, MO USA. [Goy, Andre] Hackensack Univ Med Ctr, Hackensack, NJ USA. [Jacobsen, Eric] Dana Farber Canc Inst, Boston, MA USA. [Advani, Ranjana] Stanford Univ, Stanford, CA 94305 USA. [Smith, Mitchell] Fox Chase Canc Ctr, Boston, MA USA. [Komrokji, Rami] Univ Cincinnati, Cincinnati, OH 45221 USA. [Pendergrass, Kelly] Kansas City Canc Ctr, Kansas City, MO USA. [Bolejack, Vanessa] Canc Res & Biostat, Seattle, WA USA. [Watts, Karen; Acosta, Mark] Eisai Inc, San Diego, CA 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 2007 VL 110 IS 11 MA 3449 BP 1011A EP 1011A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100804486 ER PT J AU Advani, R Hymes, K Pohlman, B Jacobsen, E McDonnell, J Belt, R Lerner, A Kim, Y Mundis, R Mansfield, T Buhl-Jensen, P Ooi, CE Duvic, M Foss, F AF Advani, Ranjana Hymes, K. Pohlman, B. Jacobsen, E. McDonnell, J. Belt, R. Lerner, A. Kim, Y. Mundis, R. Mansfield, T. Buhl-Jensen, P. Ooi, C. E. Duvic, M. Foss, F. TI Belinostat (PXD101) in patients with recurrent or refractory peripheral or cutaneous T-Cell lymphoma: Results of a phase II study SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Advani, Ranjana; Kim, Y.] Stanford Univ, Stanford, CA 94305 USA. [Hymes, K.] New York Med Ctr, New York, NY USA. [Pohlman, B.; McDonnell, J.] Cleveland Clin, Cleveland, OH USA. [Jacobsen, E.] Dana Farber Canc Inst, Boston, MA USA. [Belt, R.; Mundis, R.] Kansas City Canc Ctr, Overland Pk, KS USA. [Lerner, A.] Boston Med Ctr, Boston, MA USA. [Mansfield, T.] CuraGen Corp, Branford, CT USA. [Buhl-Jensen, P.] TopoTargets AS, Copenhagen, Denmark. [Duvic, M.] MD Anderson Canc Ctr, Houston, TX USA. [Foss, F.] Yale Univ, New Haven, CT 06520 USA. NR 0 TC 4 Z9 4 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 2007 VL 110 IS 11 MA 3453 BP 1012A EP 1012A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100804490 ER PT J AU Chauhan, D Brahmandam, M Singh, A Bianchi, G Podar, K Carrasco, R Richardson, P Munshi, N Anderson, KC AF Chauhan, Dharminder Brahmandam, Mohan Singh, Ajita Bianchi, Giada Podar, Klaus Carrasco, Ruben Richardson, Paul Munshi, Nikhil Anderson, Kenneth C. TI Plasmacytoid dendritic cells induce growth and survival of multiple myeloma cells: Therapeutic application SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Chauhan, Dharminder; Brahmandam, Mohan; Singh, Ajita; Bianchi, Giada; Podar, Klaus; Carrasco, Ruben; Richardson, Paul; Munshi, Nikhil; Anderson, Kenneth C.] Dana Faber Canc 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 2007 VL 110 IS 11 MA 3507 BP 1027A EP 1027A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100804544 ER PT J AU Driscoll, JJ Lefkimmiatis, K Fulciniti, M Prabhala, R Pelluru, D Greipp, PR Munshi, NC AF Driscoll, James J. Lefkimmiatis, Konstantinos Fulciniti, Mariateresa Prabhala, Rao Pelluru, Dheeraj Greipp, Philip R. Munshi, Nikhil C. TI Induction of UBC9 and the sumoylation pathway in multiple myeloma promotes plasma cell growth and correlates with decreased patient survival SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Driscoll, James J.; Lefkimmiatis, Konstantinos; Prabhala, Rao; Pelluru, Dheeraj; Munshi, Nikhil C.] VA Boston Hlthcare, Dept Res, W Roxbury, MA USA. [Driscoll, James J.; Fulciniti, Mariateresa; Prabhala, Rao; Pelluru, Dheeraj; Munshi, Nikhil C.] Dana Farber Canc Inst, Boston, MA USA. [Driscoll, James J.; Lefkimmiatis, Konstantinos; Fulciniti, Mariateresa; Prabhala, Rao; Pelluru, Dheeraj; Munshi, Nikhil C.] Harvard Med Sch, Boston, MA USA. [Greipp, Philip R.] Mayo Clin, Div Hematol, Rochester, MN 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 2007 VL 110 IS 11 MA 3516 BP 1030A EP 1030A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100804553 ER PT J AU Prabhala, R Pelluru, D Neri, P Fulciniti, M Driscoll, JJ Weihua, S Blotta, S Tai, YT Patel, H Efebera, YA Hideshima, T Chauhan, D Daley, JF Anderson, KC Munshi, NC AF Prabhala, Rao Pelluru, Dheeraj Neri, Paola Fulciniti, Mariateresa Driscoll, James J. Weihua, Song Blotta, Simona Tai, Yu-Tzu Patel, Hiren Efebera, Yvonne A. Hideshima, Teru Chauhan, Dhaminder Daley, John F. Anderson, Kenneth C. Munshi, Nikhil C. TI T(H)17 pathway and associated pro-inflammatory cytokines promote immune dysfunction in myeloma SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Prabhala, Rao; Pelluru, Dheeraj; Driscoll, James J.; Patel, Hiren; Efebera, Yvonne A.; Munshi, Nikhil C.] VA Boston Hlthcare Syst, HMS, W Roxbury, MA USA. [Prabhala, Rao; Pelluru, Dheeraj; Neri, Paola; Fulciniti, Mariateresa; Weihua, Song; Blotta, Simona; Tai, Yu-Tzu; Patel, Hiren; Hideshima, Teru; Chauhan, Dhaminder; Daley, John F.; Anderson, Kenneth C.; Munshi, Nikhil C.] Dana Farber Canc Inst, Boston, MA USA. RI Efebera, Yvonne/E-3012-2011 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 2007 VL 110 IS 11 MA 3517 BP 1030A EP 1030A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100804554 ER PT J AU Pozzi, S Hideshima, T Vallet, S Mukherjee, S Chhetri, S Cirstea, D Vaghela, N Thomas, C Rosa, D Ikeda, H Okawa, Y Kiziltepe, T Schoonmaker, J Schipani, E Bouxsein, M Anderson, KC Raje, N AF Pozzi, Samantha Hideshima, Teru Vallet, Sonia Mukherjee, Siddhartha Chhetri, Shweta Cirstea, Diana Vaghela, Nileshwari Thomas, Clare Rosa, Dilani Ikeda, Hiroshi Okawa, Yutaka Kiziltepe, Tanyel Schoonmaker, Jesse Schipani, Ernestina Bouxsein, Mary Anderson, Kenneth C. Raje, Noopur TI In vivo effects of zoledronic acid on bone remodeling SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Pozzi, Samantha; Hideshima, Teru; Vallet, Sonia; Chhetri, Shweta; Cirstea, Diana; Vaghela, Nileshwari; Ikeda, Hiroshi; Okawa, Yutaka; Kiziltepe, Tanyel; Anderson, Kenneth C.; Raje, Noopur] Harvard Med Sch, Dana Farber Canc Inst, Jerome Lipper Multiple Myeloma Dis Ctr, Boston, MA USA. [Mukherjee, Siddhartha; Thomas, Clare; Rosa, Dilani; Schoonmaker, Jesse; Schipani, Ernestina; Raje, Noopur] Massachusetts Gen Hosp, Harvard Med Sch, Boston, MA USA. [Bouxsein, Mary] Beth Israel Deaconess Med Ctr, Harvard Med Sch, Boston, MA USA. RI Pozzi, Samantha/A-7617-2012 OI Pozzi, Samantha/0000-0001-7917-1774 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 2007 VL 110 IS 11 MA 3520 BP 1031A EP 1031A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100804557 ER PT J AU Leleu, X Xu, L Hunter, ZR Adamia, S Hatjiharissi, E Moreau, AS Roccaro, A Sacco, A Ciccarelli, B Manning, RJ Petterson, CJ Ghobrial, IM Treon, SP AF Leleu, Xavier Xu, Lian Hunter, Zachary R. Adamia, Sophia Hatjiharissi, Evdoxia Moreau, Anne-Sophie Roccaro, Aldo Sacco, Antonio Ciccarelli, Brian Manning, Robert J. Petterson, Christopher J. Ghobrial, Irene M. Treon, Steven P. TI Biological sequelae of TRAF2 Downregulation in Waldenstrom macroglobulinemia cells SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Leleu, Xavier; Xu, Lian; Hunter, Zachary R.; Adamia, Sophia; Hatjiharissi, Evdoxia; Moreau, Anne-Sophie; Roccaro, Aldo; Sacco, Antonio; Ciccarelli, Brian; Manning, Robert J.; Petterson, Christopher J.; Ghobrial, Irene M.; Treon, Steven P.] Dana Farber Canc Inst, Bing Ctr Waldenstrom Macroglobulinemia, Boston, MA USA. [Leleu, Xavier; Moreau, Anne-Sophie] CHRU, Serv Malad Sang, Immunol Lab, Lille, France. RI Hunter, Zachary/H-3018-2013 OI Hunter, Zachary/0000-0002-1689-1691 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 2007 VL 110 IS 11 MA 3526 BP 1032A EP 1032A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100804563 ER PT J AU Moreau, AS Leleu, X Jia, X Runnels, J Pitsillides, C Carlson, AL Ngo, HT Roccaro, AM Azab, A Azab, F Lin, CP Ghobrial, IM AF Moreau, Anne-Sophie Leleu, Xavier Jia, Xiaoying Runnels, Judith Pitsillides, Costas Carlson, Alicia L. Ngo, Hai T. Roccaro, Aldo M. Azab, Abdelkareem Azab, Feba Lin, Charles P. Ghobrial, Irene M. TI Regulation of the new CXCR7 receptor in plasma cell dyscrasias SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Moreau, Anne-Sophie; Runnels, Judith; Pitsillides, Costas; Carlson, Alicia L.; Lin, Charles P.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA USA. [Moreau, Anne-Sophie; Leleu, Xavier] CHRU, Serv Malad Sang, Lille, France. [Leleu, Xavier; Jia, Xiaoying; Runnels, Judith; Ngo, Hai T.; Azab, Feba; Ghobrial, Irene M.] Dana Farber Canc Inst, Boston, MA 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 2007 VL 110 IS 11 MA 3527 BP 1032A EP 1033A PN 1 PG 2 WC Hematology SC Hematology GA 233OS UT WOS:000251100804564 ER PT J AU Gotlib, J George, TI Corless, C Linder, A Ruddell, A Akin, C DeAngelo, DJ Kepten, I Lanza, C Heinemann, H Yin, O Gallagher, N Graubert, T AF Gotlib, Jason George, Tracy I. Corless, Chris Linder, Andrea Ruddell, Alisa Akin, Cem DeAngelo, Daniel J. Kepten, Ilana Lanza, Carlo Heinemann, Heidnan Yin, Ophelia Gallagher, Neil Graubert, Tim TI The KIT tyrosine kinase inhibitor midostaurine (PKC412) exhibits a high response rate in aggressive systemic mastocytosis (ASM): Interim results of a phase II trial SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Gotlib, Jason; Linder, Andrea] Stanford Canc Ctr, Stanford, CA USA. [George, Tracy I.] Stanford Univ, Sch Med, Stanford, CA USA. [Corless, Chris; Kepten, Ilana] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Ruddell, Alisa; Graubert, Tim] Washington Univ, Sch Med, St Louis, MO 63130 USA. [Akin, Cem] Univ Michigan, Ann Arbor, MI 48109 USA. [DeAngelo, Daniel J.] Dana Farber Canc Inst, Boston, MA USA. [Lanza, Carlo; Heinemann, Heidnan; Yin, Ophelia; Gallagher, Neil] Novartis Oncol, Basel, Switzerland. NR 0 TC 10 Z9 10 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 2007 VL 110 IS 11 MA 3536 BP 1035A EP 1035A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100804573 ER PT J AU Lasho, TL Finke, C Hood, JD Soll, R Noronha, G Mesa, RA Jamieson, C Verstovsek, S Cortes, J Kantarjian, H Gilliland, DG Tefferi, A Pardanani, A AF Lasho, Terra L. Finke, Christy Hood, John D. Soll, Richard Noronha, Glenn Mesa, Ruben A. Jamieson, Catriona Verstovsek, Srdan Cortes, Jorge Kantarjian, Hagop Gilliland, D. Gary Tefferi, Ayalew Pardanani, Animesh TI Primary cell experiments with TG101348, a JAK2-selective inhibitor, in the presence of myeloproliferative disorder-associated JAK2V617F, MPLW515L/K, and JAK2 exon 12 mutations SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Lasho, Terra L.; Finke, Christy; Mesa, Ruben A.; Tefferi, Ayalew; Pardanani, Animesh] Mayo Clin, Rochester, MN USA. [Hood, John D.; Soll, Richard; Noronha, Glenn] TargeGen Inc, San Diego, CA USA. [Jamieson, Catriona] Univ Calif San Diego, San Diego, CA USA. [Verstovsek, Srdan; Cortes, Jorge; Kantarjian, Hagop] MD Anderson Canc Ctr, Houston, TX USA. [Gilliland, D. Gary] Dana Farber Canc Inst, Boston, MA 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 2007 VL 110 IS 11 MA 3541 BP 1036A EP 1036A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100804578 ER PT J AU Abonour, R Zhang, LA Rajkumar, V Srkalovic, G Greipp, PR Fonseca, R Gertz, M AF Abonour, Rafat Zhang, Lijun A. Rajkumar, Vincent Srkalovic, Gordan Greipp, Philip R. Fonseca, Rafael Gertz, Morie TI Phase II pilot study of rituximab plus CHOP in patients with newly diagnosed Waldenstrom's macroglobulinemia, an eastren cooperative oncology group trial (Study E1A02) SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Abonour, Rafat] Indiana Univ, Sch Med, Indianapolis, IN USA. [Zhang, Lijun A.; Greipp, Philip R.; Gertz, Morie] Dana Farber Canc Inst, Boston, MA 02115 USA. [Rajkumar, Vincent] Mayo Clin, Rochester, MN USA. [Srkalovic, Gordan] Sparrow Reg Canc Ctr, Lansing, MI USA. [Fonseca, Rafael] Mayo Clin, Scottsdale, AZ 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 2007 VL 110 IS 11 MA 3616 BP 1058A EP 1058A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100804653 ER PT J AU Bergmeier, W Crittenden, JR Piffath, CL Cifuni, SM Wagner, DD AF Bergmeier, Wolfgang Crittenden, Jill R. Piffath, Crystal L. Cifuni, Stephen M. Wagner, Denisa D. TI CatDAG-GEFI and protein kinase c (PKC) represent alternative pathways leading to activation of integrin alpha II beta 3 in platelets SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Bergmeier, Wolfgang; Piffath, Crystal L.; Cifuni, Stephen M.; Wagner, Denisa D.] CBR Inst Biomed Res, Boston, MA USA. [Bergmeier, Wolfgang; Wagner, Denisa D.] Harvard Med Sch, Boston, MA USA. [Crittenden, Jill R.] MIT, Ctr Canc Res, McGovern Inst Brain Res, 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 2007 VL 110 IS 11 MA 3646 BP 1066A EP 1066A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100804683 ER PT J AU Jasuja, R Furie, B Furie, BC AF Jasuja, Reerna Furie, Bruce Furie, Barbara C. TI Endothelial cell thiol isomerases: Potential role in thrombus formation. SO BLOOD LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Society-of-Hematology CY DEC 08-11, 2007 CL Atlanta, GA SP Amer Soc Hematol C1 [Jasuja, Reerna; Furie, Bruce; Furie, Barbara C.] Harvard Med Sch, BIDMC, 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 2007 VL 110 IS 11 MA 3709 BP 1083A EP 1083A PN 1 PG 1 WC Hematology SC Hematology GA 233OS UT WOS:000251100804746 ER PT J AU Wood, LD Parsons, DW Jones, S Lin, J Sjoblom, T Leary, RJ Shen, D Boca, SM Barber, T Ptak, J Silliman, N Szabo, S Dezso, Z Ustyanksky, V Nikolskaya, T Nikolsky, Y Karchin, R Wilson, PA Kaminker, JS Zhang, ZM Croshaw, R Willis, J Dawson, D Shipitsin, M Willson, JKV Sukumar, S Polyak, K Park, BH Pethiyagoda, CL Pant, PVK Ballinger, DG Sparks, AB Hartigan, J Smith, DR Suh, E Papadopoulos, N Buckhaults, P Markowitz, SD Parmigiani, G Kinzler, KW Velculescu, VE Vogelstein, B AF Wood, Laura D. Parsons, D. Williams Jones, Sian Lin, Jimmy Sjoblom, Tobias Leary, Rebecca J. Shen, Dong Boca, Simina M. Barber, Thomas Ptak, Janine Silliman, Natalie Szabo, Steve Dezso, Zoltan Ustyanksky, Vadim Nikolskaya, Tatiana Nikolsky, Yuri Karchin, Rachel Wilson, Paul A. Kaminker, Joshua S. Zhang, Zemin Croshaw, Randal Willis, Joseph Dawson, Dawn Shipitsin, Michail Willson, James K. V. Sukumar, Saraswati Polyak, Kornelia Park, Ben Ho Pethiyagoda, Charit L. Pant, P. V. Krishna Ballinger, Dennis G. Sparks, Andrew B. Hartigan, James Smith, Douglas R. Suh, Erick Papadopoulos, Nickolas Buckhaults, Phillip Markowitz, Sanford D. Parmigiani, Giovanni Kinzler, Kenneth W. Velculescu, Victor E. Vogelstein, Bert TI The genomic landscapes of human breast and colorectal cancers SO SCIENCE LA English DT Article ID SINGLE-NUCLEOTIDE POLYMORPHISMS; PIK3CA GENE; MUTATIONAL ANALYSIS; MULTIPLE-MYELOMA; HIGH-FREQUENCY; PATHWAYS; PATTERNS; PROTEIN; SEQUENCES; ONCOGENE AB Human cancer is caused by the accumulation of mutations in oncogenes and tumor suppressor genes. To catalog the genetic changes that occur during tumorigenesis, we isolated DNA from 11 breast and 11 colorectal tumors and determined the sequences of the genes in the Reference Sequence database in these samples. Based on analysis of exons representing 20,857 transcripts from 18,191 genes, we conclude that the genomic landscapes of breast and colorectal cancers are composed of a handful of commonly mutated gene "mountains" and a much larger number of gene "hills" that are mutated at low frequency. We describe statistical and bioinformatic tools that may help identify mutations with a role in tumorigenesis. These results have implications for understanding the nature and heterogeneity of human cancers and for using personal genomics for tumor diagnosis and therapy. C1 Johns Hopkins Kimmel Canc Ctr, Ludwig Ctr Canc Genet & Therapeut, Baltimore, MD 21231 USA. Johns Hopkins Kimmel Canc Ctr, Howard Hughes Med Inst, Baltimore, MD 21231 USA. Johns Hopkins Med Inst, Dept Biostat, Baltimore, MD 21231 USA. GeneGo, St Joseph, MI 49085 USA. Vavilov Inst Gen Genet, Moscow, Russia. Johns Hopkins Univ, Inst Computat Med, Dept Biomed Engn, Baltimore, MD 21218 USA. Genentech Inc, Dept Bioinformat, San Francisco, CA 94080 USA. Univ S Carolina, Sch Med, Dept Pathol & Microbiol, Ctr Colon Canc Res, Columbia, SC 29229 USA. Univ S Carolina, S Carolina Canc Ctr, Div Basic Res, Columbia, SC 29229 USA. Case Western Reserve Univ, Dept Pathol, Cleveland, OH 44106 USA. Case Western Reserve Univ, Ireland Canc Ctr, Cleveland, OH 44106 USA. Univ Hosp Cleveland, Cleveland, OH 44106 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Univ Texas, SW Med Ctr Dallas, Harold C Simmons Comprehens Canc Ctr, Dallas, TX 75390 USA. Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21231 USA. Perlegen Sci, Mountain View, CA 94043 USA. Agencourt Biosci Corp, Beverly, MA 01915 USA. Case Western Reserve Univ, Dept Med, Cleveland, OH 44106 USA. Howard Hughes Med Inst, Cleveland, OH 44106 USA. RP Parmigiani, G (reprint author), Johns Hopkins Kimmel Canc Ctr, Ludwig Ctr Canc Genet & Therapeut, Baltimore, MD 21231 USA. EM gp@jhu.edu; kinzlke@jhmi.edu; velculescu@jhmi.edu; vogelbe@welch.jhu.edu RI Karchin, Rachel/A-3385-2010; Jin, Ning/B-7956-2011; Jones, Sian/A-5050-2012; Papadopoulos, Nickolas/K-7272-2012; Nikolskaya, Tatiana/M-5008-2013 FU NCI NIH HHS [CA 43460, CA 57345, CA109274, CA112828, CA121113, CA62924, P30-CA43703]; NCRR NIH HHS [RR017698]; NIGMS NIH HHS [GM070219, GM07309] NR 32 TC 1775 Z9 1822 U1 19 U2 169 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD NOV 16 PY 2007 VL 318 IS 5853 BP 1108 EP 1113 DI 10.1126/science.1145720 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 231OC UT WOS:000250957900038 PM 17932254 ER PT J AU Gimelbrant, A Hutchinson, JN Thompson, BR Chess, A AF Gimelbrant, Alexander Hutchinson, John N. Thompson, Benjamin R. Chess, Andrew TI Widespread monoallelic expression on human autosomes SO SCIENCE LA English DT Article ID X-LINKED GENE; ASYNCHRONOUS REPLICATION; INACTIVATION; INTERLEUKIN-2; DUPLICATION; CHROMOSOME; LOCUS; MOUSE; CELLS AB Monoallelic expression with random choice between the maternal and paternal alleles defines an unusual class of genes comprising X-inactivated genes and a few autosomal gene families. Using a genome-wide approach, we assessed allele-specific transcription of about 4000 human genes in clonal cell lines and found that more than 300 were subject to random monoallelic expression. For a majority of monoallelic genes, we also observed some clonal lines displaying biallelic expression. Clonal cell lines reflect an independent choice to express the maternal, the paternal, or both alleles for each of these genes. This can lead to differences in expressed protein sequence and to differences in levels of gene expression. Unexpectedly widespread monoallelic expression suggests a mechanism that generates diversity in individual cells and their clonal descendants. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02114 USA. RP Chess, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Simches Res Bldg,185 Cambridge St, Boston, MA 02114 USA. EM chess@chgr.mgh.harvard.edu NR 24 TC 325 Z9 329 U1 4 U2 24 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD NOV 16 PY 2007 VL 318 IS 5853 BP 1136 EP 1140 DI 10.1126/science.1148910 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 231OC UT WOS:000250957900046 PM 18006746 ER PT J AU Blendea, D Mansour, M Shah, RV Chung, J Nandigam, V Heist, EK Mela, T Reddy, VY Manzke, R McPherson, CA Ruskin, JN Singh, JP AF Blendea, Dan Mansour, Moussa Shah, Ravi V. Chung, Jeffrey Nandigam, Veena Heist, E. Kevin Mela, Theofanie Reddy, Vivek Y. Manzke, Robert McPherson, Craig A. Ruskin, Jeremy N. Singh, Jagmeet P. TI Usefulness of high-speed rotational coronary venous angiography during cardiac resynchronization therapy SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CHRONIC HEART-FAILURE; COMPUTED-TOMOGRAPHY; IMPLANTATION; SINUS; EXPERIENCE; ANATOMY; LEAD AB Standard coronary venous angiography (SCVA) provides a static, fixed projection of the coronary venous (CV) tree. High-speed rotational coronary venous angiography (RCVA) is a novel method of mapping CV anatomy using dynamic, multiangle visualization. The purpose of this study was to assess the value of RCVA during cardiac resynchronization therapy. Digitally acquired rotational CV angiograms from 49 patients (mean age 69 +/- 11 years) who underwent left ventricular lead implantation were analyzed. RCVA, which uses rapid isocentric rotation over a 110 degrees arc, acquiring 120 frames/angiogram, was compared with SCVA, defined as 2 static orthogonal views: right anterior oblique 45 degrees and left anterior oblique 45 degrees. RCVA demonstrated that the posterior vein-to-coronary sinus (CS) angle and the left marginal vein-to-CS angle were misclassified in 5 and 11 patients, respectively, using SCVA. RCVA identified a greater number of second-order tributaries with diameters > 1.5 mm than SCVA. The CV branch selected for lead placement was initially identified in 100% of patients using RCVA but in only 74% of patients using SCVA. RCVA showed that the best angiographic view for visualizing the CS and its tributaries differed significantly among different areas of the CV tree and among patients. The area of the CV tree that showed less variability was the CS ostium, which had a fairly constant relation with the spine in shallow right anterior oblique and left anterior oblique projections. In conclusion, RCVA provided a more precise map of CV anatomy and the spatial relation of venous branches. It allowed the identification of fluoroscopic views that could facilitate cannulation of the CS. The final x-ray view displaying the appropriate CV branch for left ventricular lead implantation was often different from the conventional left anterior oblique and right anterior oblique views. RCVA identified the target branch for lead implantation more often than SCVA. (c) 2007 Elsevier Inc. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Cardiac Arrhythmia Serv, Boston, MA 02115 USA. Yale Univ, Sch Med, Bridgeport Hosp, Div Cardiol, Bridgeport, CT USA. Philips Res N Amer, Clin Sites Res Program, Boston, MA USA. RP Singh, JP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Cardiac Arrhythmia Serv, Boston, MA 02115 USA. EM jsingh@partners.org NR 23 TC 16 Z9 17 U1 0 U2 0 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD NOV 15 PY 2007 VL 100 IS 10 BP 1561 EP 1565 DI 10.1016/j.amjcard.2007.06.062 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 236HT UT WOS:000251294500013 PM 17996520 ER PT J AU Auricchio, A Sorgente, A Singh, JP Faletra, F Conca, C Pedrazzini, GB Pasotti, E Siclari, F Moccetti, T AF Auricchio, Angelo Sorgente, Antonio Singh, Jagmeet P. Faletra, Francesco Conca, Cristina Pedrazzini, Giovanni B. Pasotti, Elena Siclari, Francesco Moccetti, Tiziano TI Role of multislice computed tomography for preprocedural evaluation before revision of a chronically implanted transvenous left ventricular lead SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CARDIAC RESYNCHRONIZATION THERAPY; VISUALIZATION; ANGIOGRAPHY; ANATOMY; DELAY AB The purpose of this study was to determine the feasibility of multislice computed tomography (MSCT) to assess the coronary sinus (CS) and its tributaries in patients who are undergoing cardiac resynchronization therapy and need a left ventricular (LV) lead revision. Preprocedural imaging modality, which may enable delineation of the cardiac venous anatomy in patients who need LV lead replacement, has not yet been evaluated. Ten patients with heart failure with previously implanted cardiac resynchronization therapy devices, who presented with worsening heart failure, were studied with MSCT and tissue Doppler imaging echocardiography before LV lead replacement. MSCT was performed to evaluate patency of the CS and coronary veins, and tissue Doppler imaging echocardiography assessed the region and the magnitude of mechanical dyssynchrony. An excellent concordance in the vein diameter, location, and status between MSCT and angiography was found. Apart from the need to perform a venoplasty in 1 patient and an unsuccessful lead explantation in another patient, all other anatomic issues were correctly predicted by MSCT. CS or vein occlusion were present in 4 patients, and in 3 of them surgical LV lead replacement was performed. Identification of a patent venous system enabling successful transvenous lead implantation was possible in 2 patients. Direct visualization of the proximity of the target vein to the phrenic nerve and the diaphragm guided lead selection and position in 4 patients. In conclusion, MSCT may be used to delineate the coronary venous anatomy in patients in whom LV lead replacement is needed to help strategize whether a transvenous or transthoracic approach may be preferred for LV lead revision. (c) 2007 Elsevier Inc. All rights reserved. C1 Fdn Cardioctr Ticino, Div Cardiol, Lugano, Switzerland. Fdn Cardioctr Ticino, Div Cardiac Surg, Lugano, Switzerland. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Heart,Cardiac Resynchronizat Therapy Program, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiac Arrhythmia Serv, Boston, MA USA. RP Auricchio, A (reprint author), Fdn Cardioctr Ticino, Div Cardiol, Lugano, Switzerland. EM angelo.auricchio@cardiocentro.org NR 16 TC 9 Z9 9 U1 0 U2 0 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD NOV 15 PY 2007 VL 100 IS 10 BP 1566 EP 1570 DI 10.1016/j.amjcard.2007.06.065 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 236HT UT WOS:000251294500014 PM 17996521 ER PT J AU Cadle, RM Mansouri, MD Logan, N Kudva, DR Musher, DA AF Cadle, Richard M. Mansouri, Mohammad D. Logan, Nancy Kudva, Denise R. Musher, Daniel A. TI Association of proton-pump inhibitors with outcomes in Clostridium difficile colitis SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Article DE antiinfective agents; clostridium infections; combined therapy; enterocolitis; gastrointestinal drugs; toxicity ID DIARRHEA; DISEASE; RISK; METRONIDAZOLE; NITAZOXANIDE; DIAGNOSIS; THERAPY AB Purpose. The role of concurrent use of proton-pump inhibitors (PPIs) in the outcomes of treatment for Clostridium difficile colitis was studied. Methods. The records of inpatients at a large Veterans Affairs medical center in whom C. difficile colitis was diagnosed between June 2004 and July 2005 were retrospectively reviewed. Data collected included patient characteristics at baseline, antibiotic therapy prescribed before and during therapy for C. difficile colitis, concurrent treatment with a PPI, response to therapy for C. difficile colitis, and recurrence of the disease in the 90 days after symptoms resolved. Outcomes of therapy were classified as cures, treatment failures, or disease recurrences. Results. A total of 140 patients (138 men and 2 women) were included in the study. Ninety-seven (69%) of patients received a PPI and 43 (31%) did not. Of patients receiving a PPI, 37 (38%) were cured of C. difficile colitis, 20 (21%) did not respond to therapy, and 40 (41%) had disease recurrence. Among the non-PPI patients, 27 (63%) were cured, 9 (21%) did not respond, and 7 (16%) had recurrence. Patients receiving PPIs were 4.17 times as likely to have recurrence as their counterparts who did not. Conclusion. PPI therapy was associated with an increased risk of recurrent C. difficile colitis. C1 Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. Baylor Coll Med, Infect Dis Sect, Houston, TX USA. Univ Texas Austin, Austin, TX USA. Univ Houston, Sch Pharm, Houston, TX USA. Baylor Coll Med, Dept Phys Med & Rehabilitat, MEDVAMC, Houston, TX USA. MD Anderson Hosp, Sect Infect Dis, MEDVAMC, Houston, TX USA. MD Anderson Hosp, Serv Pharm, Houston, TX USA. RP Cadle, RM (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Serv Pharm, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM cadle.richardmark@med.va.gov NR 19 TC 59 Z9 63 U1 1 U2 6 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 2007 VL 64 IS 22 BP 2359 EP 2363 DI 10.2146/ajhp060629 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 234XO UT WOS:000251198000013 PM 17989446 ER PT J AU Abo-Dalo, B Kim, HG Roes, M Stefanova, M Higgins, A Shen, Y Mundlos, S Quade, BJ Gusella, JF Kutsche, K AF Abo-Dalo, Benjamin Kim, Hyung-Goo Roes, Melanie Stefanova, Margarita Higgins, Anne Shen, Yiping Mundlos, Stefan Quade, Bradley J. Gusella, James F. Kutsche, Kerstin TI Extensive molecular genetic analysis of the 3p14.3 region in patients with Zimmermann-Laband syndrome SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE zimmermann-Laband syndrome; WNT5A; CACAA2D3; chromosome translocation; gingival hyperplasia ID CIS-ACTING REGULATOR; MENTAL-RETARDATION; SONIC HEDGEHOG; EXPRESSION; RANGE; LIMB; SHH; TRANSLOCATION; DISRUPTION; DISEASE AB Zimmermann-Laband syndrome (ZLS) is a rare autosomal dominant inherited disorder characterized by a coarse facial appearance, gingival fibromatosis, and absence or hypoplasia of the terminal phalanges and nails of hands and feet. Additional, more variable features include hyperextensibility of joints, hepatosplenomegaly, mild hirsutism, and mental retardation. Mapping of the translocation breakpoints of t(3;8) and t(3;17) found in patients with the typical clinical features of ZLS defined a common breakpoint region of similar to 280 kb located in 3p14.3, which includes the genes CACNA2D3 and WNT5A. Breakpoint cloning revealed that both translocations most likely occurred by non-homologous (illegitimate) recombination. Mutation analysis of nine genes located in 3p21.1-p14.3, including CACNA2D3, which is directly disrupted by one breakpoint of the t(3;17), identified no pathogenic mutation in eight sporadic patients with ZLS. Southern hybridization analysis and multiplex ligation-dependent probe amplification (MLPA) did not detect submicroscopic deletion or duplication in either CACNA2D3 or WNT5A in ZLS-affected individuals. Mutation analysis of nine conserved nongenic sequence elements (CNEs) in 3p21.1-p14.3, which were identified by interspecies comparison and may represent putative regulatory elements for spatiotemporally correct expression of nearby genes, did not show any sequence alteration associated with ZLS. Taken together, the lack of a specific coding-sequence lesion in the common region, defined by two translocation breakpoints, in sporadic patients with ZLS and an apparently normal karyotype suggests that either some other type of genetic defect in this vicinity or an alteration elsewhere in the genome could be responsible for ZLS. (C) 2007 Wiley-Liss, Inc. C1 Univ Klinikum Hamburg Eppendorf, Inst Humangenet, D-20246 Hamburg, Germany. Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Genet, Ctr Human Genet Res,Mol Neurogenet Unit, Cambridge, MA 02138 USA. Med Univ, Dept Med Genet, Plovdiv, Bulgaria. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Max Planck Inst Mol Genet, Berlin, Germany. RP Kutsche, K (reprint author), Univ Klinikum Hamburg Eppendorf, Inst Humangenet, Campus Forsch,Gebaude 146,Martinistr 52, D-20246 Hamburg, Germany. EM kkutsche@uke.uni-hamburg.de FU NICHD NIH HHS [HD28138]; NIGMS NIH HHS [GM061354] NR 34 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 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD NOV 15 PY 2007 VL 143A IS 22 BP 2668 EP 2674 DI 10.1002/ajmg.a.32034 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 228EA UT WOS:000250708900006 PM 17937436 ER PT J AU Bao, YW Zhu, LB Newburg, DS AF Bao, Yuanwu Zhu, Libin Newburg, David S. TI Simultaneous quantification of sialyloligosaccharides from human milk by capillary electrophoresis SO ANALYTICAL BIOCHEMISTRY LA English DT Article DE human milk oligosaccharides; sialyloligosaccharides; capillary electrophoresis ID ANION-EXCHANGE CHROMATOGRAPHY; PULSED AMPEROMETRIC DETECTION; PERFORMANCE LIQUID-CHROMATOGRAPHY; SIALYLATED OLIGOSACCHARIDES; SEPARATION; LACTATION; DERIVATIVES; COLOSTRUM; MIXTURES; INFANTS AB The acidic oligosaccharides of human milk are predominantly sialyloligosaccharides. Pathogens that bind sialic acid-containing glycans on their host mucosal surfaces may be inhibited by human milk sialyloligosaccharides, but testing this hypothesis requires their reliable quantification in milk. Sialyloligosaccharides have been quantified by anion exchange high-performance liquid chromatography (HPLC), reverse- or normal-phase HPLC, and capillary clectrophoresis (CE) of fluorescent derivatives; in milk, these oligosaccha rides have been analyzed by high pH anion exchange chromatography with pulsed amperometric detection and, in our laboratory, by CE with detection at 205 nm. The novel method described here uses a running buffer of aqueous 200 mM NaH2PO4 (pH 7.05) containing 100 mM sodium dodecyl sulfate (SDS) mixed with 45% (v/v) methanol to baseline resolve 5 oligosaccharides and separate all 12. This allows automated simultaneous quantification of the 12 major sialyloligosaccharides of human milk in a single 35-min run. This method revealed differences in sialyloligosaccharide concentrations between less and more mature milk from the same donors. Individual donors also varied in expression of sialyl oligo saccha rides in their milk. Thus, the facile quantification of sialyloligosaccharides by this method is suitable for measuring variation in expression of specific sialyloligosaccharides in milk and their relationship to decreased risk of specific diseases in infants. (c) 2007 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Newburg, DS (reprint author), Massachusetts Gen Hosp, Charlestown, MA 02129 USA. EM dnewburg@partners.org FU NICHD NIH HHS [HD13021, HD12437, P01 HD013021, P01 HD013021-260013, P01 HD013021-269007, R37 HD012437, R37 HD012437-27]; NIDDK NIH HHS [DK40561, P30 DK040561, P30 DK040561-129004] NR 30 TC 36 Z9 38 U1 5 U2 17 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD NOV 15 PY 2007 VL 370 IS 2 BP 206 EP 214 DI 10.1016/j.ab.2007.07.004 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 221EN UT WOS:000250210300010 PM 17761135 ER PT J AU Carpenter, LL Carvalho, JP Tyrka, AR Wier, LM Mello, AF Mello, MF Anderson, GM Wilkinson, CW Price, LH AF Carpenter, Linda L. Carvalho, John P. Tyrka, Audrey R. Wier, Lauren M. Mello, Andrea F. Mello, Marcelo F. Anderson, George M. Wilkinson, Charles W. Price, Lawrence H. TI Decreased adrenocorticotropic hormone and cortisol responses to stress in healthy adults reporting significant childhood maltreatment SO BIOLOGICAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 44th Annual Meeting of the American-College-Neuropsychopharmacology CY DEC 11-15, 2005 CL Waikoloa, HI SP Vanderbilt Univ, Sch Med, Dept Psychiat DE abuse; ACTH; childhood; cortisol; enclophenotype; HPA axis; reactivity; trier social stress test ID PITUITARY-ADRENAL AXIS; MAJOR DEPRESSIVE DISORDER; EARLY ADVERSE EXPERIENCE; CHRONIC VARIABLE STRESS; PSYCHOSOCIAL STRESS; SOCIAL STRESS; NEUROENDOCRINE ACTIVITY; PSYCHOLOGICAL STRESS; PERCEIVED STRESS; CHALLENGE TESTS AB Background: Preclinical research findings suggest that exposure to stress and concomitant hypothalamus-pituitary-ad renal (HPA) axis activation during early development can have permanent and potentially deleterious effects. A history of early-life abuse or neglect appears to increase risk for mood and anxiety disorders. Abnormal HPA response to stress challenge has been reported in adult patients with major depressive disorder and posttraumatic stress disorder. Methods: Plasma adrenocorticotropin hormone (ACTH) and cortisol reactivity to the Trier Social Stress Test were examined in healthy adults (n = 50) without current psychopathology. Subjects with a self-reported history of moderate to severe childhood maltreatment (MAL) (n = 23) as measured by the Childhood Trauma Questionnaire were compared with subjects without such a history (CTL) (n = 27). Results: Compared with CTLs, MAL subjects exhibited significantly lower cortisol and ACTH baseline-to-peak deltas. A significant group effect was seen in the (repeated measures) cortisol response to the stress challenge, reflecting lower concentrations among MAL subjects. A significant group X time effect characterized the relatively blunted ACTH response of the MAL group. Emotional neglect (-.34, p = .02) and sexual abuse (.31, p = .03) strongly predicted maximal cortisol release. Conclusions: In adults without diagnosable psychopathology, childhood maltreatment is associated with diminished HPA axis response to a psychosocial stressor. Possible explanations for the finding are discussed. C1 Butler Hosp, Mood Disorders Res Program, Providence, RI 02906 USA. Butler Hosp, Lab Clin Neurosci, Providence, RI 02906 USA. Brown Univ, Sch Med, Dept Psychiat & Human Behav, Providence, RI 02912 USA. Yale Univ, Sch Med, Ctr Child Study, New Haven, CT 06510 USA. Univ Washington, Ctr Geriatr Res Educ & Clin, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. RP Carpenter, LL (reprint author), Butler Hosp, Mood Disorders Res Program, 345 Blackstone Blvd, Providence, RI 02906 USA. RI Tyrka, Audrey/L-2504-2014; Mello, Andrea/Q-1795-2015; Mello, Marcelo/D-9565-2011 OI Mello, Marcelo/0000-0002-0475-4729 FU NIMH NIH HHS [R01 MH068767, R01 MH068767-01, R01 MH068767-01A1, R01 MH068767-02] NR 79 TC 206 Z9 209 U1 6 U2 33 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 2007 VL 62 IS 10 BP 1080 EP 1087 DI 10.1016/j.biopsych.2007.05.002 PG 8 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 230WB UT WOS:000250905800003 PM 17662255 ER PT J AU Fu, Q Koenen, KC Miller, MW Heath, AC Bucholz, KK Lyons, MJ Eisen, SA True, WR Goldberg, J Tsuang, MT AF Fu, Qiang Koenen, Karestan C. Miller, Mark W. Heath, Andrew C. Bucholz, Kathleen K. Lyons, Michael J. Eisen, Seth A. True, William R. Goldberg, Jack Tsuang, Ming T. TI Differential etiology of posttraumatic stress disorder with conduct disorder and major depression in male veterans SO BIOLOGICAL PSYCHIATRY LA English DT Article DE conduct disorder; major depression; posttraumatic stress disorder ID ERA TWIN REGISTRY; PSYCHIATRIC-DISORDERS; TRAUMA EXPOSURE; RISK-FACTORS; ENVIRONMENTAL-INFLUENCES; INTERNALIZING SUBTYPES; SOCIOECONOMIC-STATUS; ANTISOCIAL-BEHAVIOR; ALCOHOL DEPENDENCE; VET REGISTRY AB Background: Epidemiologic studies reveal that posttraumatic stress disorder (PTSD) is highly comorbid with both conduct disorder and major depression in men. The genetic and environmental etiology of this comorbidity has not been examined. Methods: Data were analyzed from 6744 middle-aged male-male monozygotic and dizygotic twins from the Vietnam Era Twin Registry. Conduct disorder, major depression, and PTSD were assessed via telephone interview using the Diagnostic Interview Schedule for the DSM-III-R in 1992. Structural equation modeling was used to estimate additive genetic, shared environmental, and individual-specific environmental effects common and specific to conduct disorder, major depression, and PTSD. Results: The association between conduct disorder and PTSD was explained primarily by common shared environmental influences; these explained 10% (95% confidence interval: 6%-17%) of the variance in PTSD. The association between major depression and PTSD was largely explained by common genetic influences; these explained 19% (95% confidence interval: 11%-26%) of the variance in PTSD. Conclusions: Our findings suggest that different etiologic mechanisms explain the association of conduct disorder and major depression with PTSD in male veterans. If replicated in other populations, results suggest research aimed at identifying specific genetic and environmental factors that influence PTSD may benefit from starting with those that have been more consistently and strongly associated with major depression and conduct disorder. C1 St Louis Univ, Sch Publ Hlth, Dept Community Hlth, St Louis, MO 63104 USA. Harvard Univ, Sch Publ Hlth, Dept Soc, Cambridge, MA 02138 USA. Harvard Univ, Sch Publ Hlth, Dept Human Dev, Cambridge, MA 02138 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth, Cambridge, MA 02138 USA. Boston Univ, Sch Med, Dept Psychiat, Boston, MA 02215 USA. VA Boston Healthcare Syst, Natl Ctr PTSD, Behav Sci Div, Boston, MA USA. Washington Univ, Midwest Alcoholism Res Ctr, St Louis, MO USA. Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. Boston Univ, Dept Psychol, Boston, MA 02215 USA. Harvard Univ, Inst Psychiat Epidemiol & Genet, Cambridge, MA 02138 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Mental Hlth Ctr, Dept Psychiat, Boston, MA USA. Univ Washington, Sch Med, Dept Internal Med, Seattle, WA 98195 USA. St Louis VA Med Ctr, Res & Med Serv, St Louis, MO USA. Vietnam Era Twin Registry, Seattle VA Epidemiol Res & Informat Ctr, Seattle, WA USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Univ Calif San Diego, Sch Med, San Diego, CA 92103 USA. RP Fu, Q (reprint author), St Louis Univ, Sch Publ Hlth, Dept Community Hlth, 3545 Lafayette Ave,Suite 300, St Louis, MO 63104 USA. EM qjfu@slu.edu RI Lyons, Michael/B-6119-2011; Miller, Mark/G-7322-2011; OI Miller, Mark/0000-0001-6393-8563; Lyons, Michael/0000-0001-6516-9219 FU NCI NIH HHS [K07 CA104119-02, K07 CA104119, K07CA104119]; NIMH NIH HHS [K08 MH070627, K08MH070627] NR 56 TC 27 Z9 27 U1 5 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD NOV 15 PY 2007 VL 62 IS 10 BP 1088 EP 1094 DI 10.1016/j.biopsych.2007.04.036 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 230WB UT WOS:000250905800004 PM 17617384 ER PT J AU Golier, JA Schmeidler, J Legge, J Yehuda, R AF Golier, Julia A. Schmeidler, James Legge, Juliana Yehuda, Rachel TI Twenty-four hour plasma cortisol and adrenocorticotropic hormone in Gulf War Veterans: Relationships to posttraumatic stress disorder and health symptoms SO BIOLOGICAL PSYCHIATRY LA English DT Article DE ACTH; Gulf War illness; medically unexplained illnesses; PTSD; stress ID CORTICOTROPIN-RELEASING HORMONE; OPERATION DESERT-STORM; MULTISYMPTOM ILLNESS; URINARY CORTISOL; DEXAMETHASONE; EXPOSURES; EXCRETION AB Background: We aim to characterize the baseline functioning of the hypothalamic-pituitary-adrenal (HPA) axis in Gulf War veterans (GWV) and examine the extent to which posttraumatic stress disorder (PTSD) and unexplained health symptoms-which commonly co-occur-have similar or different biological correlates. Methods: Thirty-one GWV, 20 with current PTSD and 11 without current or lifetime PTSD, and 16 healthy nondeployed subjects not exposed to the Gulf War theater underwent medical and psychiatric examination followed by blood sampling every half-hour over 24 hours for the measurement of cortisol and adrenocorticotropic hormone (ACTH). Results: Gulf War veterans without PTSD or another psychiatric disorder had significantly lower 24-hour plasma ACTH levels, a significantly higher cortisol:ACTH ratio, and no difference in cortisol levels compared to nondeployed subjects and to GWV with PTSD, controlling for body mass index (BMI). Among GWV, health symptoms (mood and cognitive symptoms) were positively associated with, and hyperarousal symptoms were negatively associated with, the cortisol:ACTH ratio. Additionally, the self-reported acute effects of pesticides and of pyridostigmine bromide during deployment were associated with lower ACTH levels, controlling for BMI and PTSD. Conclusions: The data provide evidence of HPA axis dysregulation in Gulf War veterans, which may be related to Gulf War deployment exposures. Despite the overlap of chronic unexplained health symptoms and PTSD in GWV, these symptom constellations appear to be biologically distinct. C1 OOMH, James J Peters VA Med Ctr, Dept Psychiat, Bronx, NY 10468 USA. CUNY Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. RP Golier, JA (reprint author), OOMH, James J Peters VA Med Ctr, Dept Psychiat, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM Julia.golier@va.gov FU NCRR NIH HHS [5 M01 RR00071] NR 30 TC 35 Z9 38 U1 0 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 2007 VL 62 IS 10 BP 1175 EP 1178 DI 10.1016/j.biopsych.2007.04.027 PG 4 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 230WB UT WOS:000250905800016 PM 17612507 ER PT J AU Milad, MR Quirk, GJ Pitman, RK Orr, SP Fischl, B Rauch, SL AF Milad, Mohammed R. Quirk, Gregory J. Pitman, Roger K. Orr, Scott P. Fischl, Bruce Rauch, Scott L. TI A role for the human dorsal anterior Cingulate cortex in fear expression SO BIOLOGICAL PSYCHIATRY LA English DT Article DE classical; conditioning; fear; galvanic skin response; gyrus cinguli; magnetic resonance imaging; memory ID MEDIAL PREFRONTAL CORTEX; FUNCTIONAL MAGNETIC-RESONANCE; SKIN-CONDUCTANCE RESPONSES; HUMAN AMYGDALA ACTIVITY; CONDITIONED FEAR; ELECTRODERMAL ACTIVITY; NEUROCIRCUITRY MODELS; EXTINCTION MEMORY; PROJECTIONS; LESIONS AB Background: Rodent studies implicate the prelimbic (PL) region of the medial prefrontal cortex in the expression of conditioned fear. Human studies suggest that the dorsal anterior cingulate cortex (dACC) plays a role similar to PL in mediating or modulating fear responses. This study examined the role of dACC during fear conditioning in healthy humans with magnetic resonance imaging (MRI). Methods: Novel analyses were conducted on data from two cohorts that had previously undergone scanning to study fear extinction. Structural and functional brain data were acquired with MRI; the functional MRI (fMRI) component employed an event-related design. Skin conductance response (SCR) was the index of conditioned responses. Results: We found that: 1) cortical thickness within dACC is positively correlated with SCR during conditioning; 2) dACC is activated by a conditioned fear stimulus; and 3) this activation is positively correlated with differential SCR. Moreover, the dACC region implicated in this research corresponds to the target of anterior cingulotomy, an ablative surgical treatment for patients with mood and anxiety disorders. Conclusions: Convergent structural, functional, and lesion findings from separate groups of subjects suggest that dACC mediates or modulates fear expression in humans. Collectively, these data implicate this territory as a potential target for future anti-anxiety therapies. C1 Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Nucl Magenet Resonance Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. McLean Hosp, Belmont, MA 02178 USA. Univ Puerto Rico, Sch Med, Dept Psychiat, San Juan, PR 00936 USA. Dept Vet Affairs Med Ctr, Res Serv, Manchester, NH USA. RP Milad, MR (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Bldg 149,13th St,2nd Floor, Charlestown, MA 02129 USA. EM milad@nmr.mgh.harvard.edu FU NIMH NIH HHS [1R21MH072156-1] NR 41 TC 198 Z9 203 U1 1 U2 24 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 2007 VL 62 IS 10 BP 1191 EP 1194 DI 10.1016/j.biopsych.2007.04.032 PG 4 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 230WB UT WOS:000250905800020 PM 17707349 ER PT J AU Richardson, PG Sonneveld, P Schuster, M Irwin, D Stadtmauer, E Facon, T Harousseau, JL Ben-Yehuda, D Lonial, S Goldschmidt, H Reece, D Miguel, JS Blade, J Boccadoro, M Cavenagh, J Alsina, M Rajkumar, SV Lacy, M Jakubowiak, A Dalton, W Boral, A Esseltine, DL Schenkein, D Anderson, KC AF Richardson, Paul G. Sonneveld, Pieter Schuster, Michael Irwin, David Stadtmauer, Edward Facon, Thierry Harousseau, Jean-Luc Ben-Yehuda, Dina Lonial, Sagar Goldschmidt, Hartmut Reece, Donna Miguel, Jesus San Blade, Joan Boccadoro, Mario Cavenagh, Jamie Alsina, Melissa Rajkumar, S. Vincent Lacy, Martha Jakubowiak, Andrzej Dalton, William Boral, Anthony Esseltine, Dixie-Lee Schenkein, David Anderson, Kenneth C. TI Extended follow-up of a phase 3 trial in relapsed multiple myeloma: final time-to-event results of the APEX trial SO BLOOD LA English DT Article ID HIGH-DOSE DEXAMETHASONE; I-II TRIAL; LIPOSOMAL DOXORUBICIN; ORAL CYCLOPHOSPHAMIDE; REFRACTORY MYELOMA; EFFECTIVE REGIMEN; I/II TRIAL; BORTEZOMIB; COMBINATION; THALIDOMIDE AB Initial analysis of the Assessment of Proteasome Inhibition for Extending Remissions (APEX) trial of relapsed multiple myeloma patients showed significantly longer time to progression, higher response rate, and improved survival with single-agent bortezomib versus high-dose dexamethasone. In this updated analysis (median follow-up: 22 months), survival was assessed in both arms, and efficacy updated for the bortezomib arm. Median survival was 29.8 months for bortezomib versus 23.7 months for dexamethasone, a 6-month benefit, despite substantial crossover from dexamethasone to bortezomib. Overall and complete response rates with bortezomib were 43% and 9%, respectively; among responding patients, 56% improved response with longer therapy beyond initial response, leading to continued improvement in overall quality of response. Higher response quality (100% M-protein reduction) was associated with longer response duration; response duration was not associated with time to response. These data confirm the activity of bortezomib and support extended treatment in relapsed multiple myeloma patients tolerating therapy. This study is registered at http://clinicaltrials.gov (Study ID NCT00048230). C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Rotterdam Hosp, Rotterdam, Netherlands. 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. Univ Nantes, Ctr Hosp, Hotel Dieu, Nantes, France. Hadassah Univ Hosp, IL-91120 Jerusalem, Israel. Emory Univ, Atlanta, GA 30322 USA. Univ Heidelberg, Heidelberg, Germany. Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. Univ Hosp, Salamanca, Spain. Univ Barcelona, Barcelona, Spain. Univ Turin, Turin, Italy. St Bartholomews Hosp, London, England. H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. Mayo Clin, Rochester, MN USA. Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI USA. Millenium Pharmacuet, Cambridge, MA USA. Genetech, San Francisco, CA USA. RP Richardson, PG (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. EM paul_richardson@dfci.harvard.edu RI 2007, Secribsal/A-1556-2012; FACON, THIERRY/M-9736-2014; OI FACON, THIERRY/0000-0001-7705-8460; Rajkumar, S. Vincent/0000-0002-5862-1833 NR 24 TC 322 Z9 343 U1 0 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 2007 VL 110 IS 10 BP 3557 EP 3560 DI 10.1182/blood-2006-08-036947 PG 4 WC Hematology SC Hematology GA 231KS UT WOS:000250946300019 PM 17690257 ER PT J AU Ishikawa, F Niiro, H Iino, T Yoshida, S Saito, N Onohara, S Miyamoto, T Minagawa, H Fujii, SI Shultz, LD Harada, M Akashi, K AF Ishikawa, Fumihiko Niiro, Hiroaki Iino, Tadafumi Yoshida, Shuro Saito, Noriyuki Onohara, Shinya Miyamoto, Toshihiro Minagawa, Hiroko Fujii, Shin-Ichiro Shultz, Leonard D. Harada, Mine Akashi, Koichi TI The developmental program of human dendritic cells is operated independently of conventional myeloid and lymphoid pathways SO BLOOD LA English DT Article ID COMMON PRECURSOR POPULATION; INTERFERON-PRODUCING CELLS; BLOOD MONONUCLEAR-CELLS; CORD BLOOD; T-CELLS; HEMATOPOIETIC PRECURSORS; COMMITTED PROGENITORS; MESSENGER-RNA; I INTERFERON; HUMAN THYMUS AB Two distinct dendritic cell (DC) subsets, conventional DCs (cDCs) and plasmacytoid DCs (pDCs), have been shown to develop via either the myeloid or the lymphoid pathway in murine hematopolesis. Lineage-specific phenotypes or functions of "myeloid" and "lymphoid" DCs, however, still remain elusive. Furthermore, such analysis has been particularly difficult in humans, due to lack of an assay system appropriate for the analysis of human stem and progenitor cell differentiation. Here, using a highly efficient xenotransplantation model, we extensively analyze the origin and the molecular signature of human DCs. Purified human common myeloid progenitors (CMPs) and common lymphoid progenitors (CLPs) were intravenously transplanted into nonobese diabetic-severe combined immunodeficiency (NOD-scid)/lL2r gamma(null) newborn mice. CMPs and CLPs displayed significant expansion in the xenogeneic host, and human cDC and pDC progeny were isolatable. Strikingly, each human DC subset possessed indistinguishable expression patterns of surface phenotype and gene transcripts regardless of their CMP or CLP origin, even at the genome-wide level. Thus, cDC and pDC normally develop after cells have committed to the myeloid or the lymphoid lineage in human hematopoiesis, while their transcriptional signatures are well preserved irrespective of their lineage origin. We propose that human DCs use unique and flexible developmental programs that cannot be categorized into the conventional myeloid or lymphoid pathway. C1 Rikagaku Kenkyusho Res Ctr Allergy & Immunol, Res Unit Human Dis, Yokohama, Kanagawa, Japan. Kyushu Univ, Grad Sch Med Sci, Dept Med & Biosyst Sci, Fukuoka 812, Japan. Kyushu Univ Hosp, Ctr Cellular & Mol Med, Fukuoka 812, Japan. Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Aichi Prefectural Inst Publ Hlth, Div Microbiol, Nagoya, Aichi 462, Japan. RIKEN, Res Ctr Allergy & Immunol, Yokohama, Kanagawa, Japan. Jackson Lab, Bar Harbor, ME 04609 USA. RP Akashi, K (reprint author), Rikagaku Kenkyusho Res Ctr Allergy & Immunol, Res Unit Human Dis, Yokohama, Kanagawa, Japan. EM akashi@cancer.med.kyushu-u.ac.jp RI 石川, 文彦/L-4488-2014; Fujii, Shin-ichiro/O-6218-2015 NR 54 TC 54 Z9 56 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 15 PY 2007 VL 110 IS 10 BP 3591 EP 3600 DI 10.1182/blood-2007-02-071613 PG 10 WC Hematology SC Hematology GA 231KS UT WOS:000250946300024 PM 17664352 ER PT J AU Wang, CY Faloon, PW Tan, ZJ Lv, YX Zhang, PB Ge, Y Deng, HK Xiong, JW AF Wang, Chengyan Faloon, Patrick W. Tan, Zhijia Lv, Yaxin Zhang, Pengbo Ge, Yu Deng, Hongkui Xiong, Jing-Wei TI Mouse lysocardiolipin acyltransferase controls the development of hematopoietic and endothelial lineages during in vitro embryonic stem-cell differentiation SO BLOOD LA English DT Article ID TRANSCRIPTION FACTOR; GROWTH-FACTOR; ES CELLS; DEFINITIVE HEMATOPOIESIS; PROTEIN PALMITOYLATION; SIGNAL-TRANSDUCTION; COMMON PRECURSOR; PRIMITIVE STREAK; HEDGEHOG SIGNAL; ZEBRAFISH GENE AB The blast colony-forming cell (BL-CFC) was identified as an equivalent to the hemangioblast during in vitro embryonic stem (ES) cell differentiation. However, the molecular mechanisms underlying the generation of the BL-CFC remain largely unknown. Here we report the isolation of mouse lysocardiolipin acyltransferase (Lycat) based on homology to zebrafish lycat, a candidate gene for the cloche locus. Mouse Lycat is expressed in hematopoietic organs and is enriched in the Lin(-)C-Kit(+)Sca-1(+) hematopoietic stem cells in bone marrow and in the Flk1(+)/hCD4(+)(Scl(+)) hemangioblast population in embryoid bodies. The forced Lycattransgene leads to increased messenger RNA expression of hematopoietic and endothelial genes as well as increased blast colonies and their progenies, endothelial and hematopoietic lineages. The Lycat small interfering RNA transgene leads to a decrease expression of hernatopoietic and endothelial genes. An unbiased genome-wide microarray analysis further substantiates that the forced Lycat transgene specifically up-regulates a set of genes related to hemangioblasts and hematopoietic and endothelial lineages. Therefore, mouse Lycat plays an important role in the early specification of hematopoietic and endothelial cells, probably acting at the level of the hemangioblast. C1 Peking Univ, Coll Life Sci, Key Lab Cell Proliferat & Differentat Minist Educ, Beijing, Peoples R China. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Harvard Med Sch, Div Nephrol, Charlestown, MA USA. RP Xiong, JW (reprint author), Peking Univ, Coll Life Sci, Key Lab Cell Proliferat & Differentat Minist Educ, Beijing, Peoples R China. EM hongkui_deng@pku.edu.cn; xiong@cvrc.mgh RI Xiong, Jing-Wei/A-7113-2011 FU NIA NIH HHS [K01 AG019676, K01 AG19676, K01 AG019676-04] NR 87 TC 18 Z9 22 U1 0 U2 8 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 2007 VL 110 IS 10 BP 3601 EP 3609 DI 10.1182/blood-2007-04-086827 PG 9 WC Hematology SC Hematology GA 231KS UT WOS:000250946300025 PM 17675553 ER PT J AU Wu, L Maillard, I Nakamura, M Pear, WS Griffin, JD AF Wu, Lizi Maillard, Ivan Nakamura, Makoto Pear, Warren S. Griffin, James D. TI The transcriptional coactivator Mam11 is required for Notch2-mediated marginal zone B-cell development SO BLOOD LA English DT Article ID ALPHA-BETA; LYMPHOCYTE DEVELOPMENT; NOTCH RECEPTORS; PRE-TCR; IN-VIVO; MASTERMIND; DIFFERENTIATION; FATE; DELTA; IDENTIFICATION AB Signaling mediated by various Notch receptors and their ligands regulates diverse biological processes, including lymphoid cell fate decisions. Notch1 is required during T-cell development, while Notch2 and the Notch ligand Delta-likel1 control marginal zone B (MZB) cell development. We previously determined that Mastermind-like (MAML) transcriptional coactivators are required for Notch-induced transcription by forming ternary nuclear complexes with Notch and the transcription factor CSL. The 3 MAML family members (MAML1-MAML3) are collectively essential for Notch activity in vivo, but whether individual MAMLs contribute to the specificity of Notch functions is unknown. Here, we addressed this question by studying lymphopoiesis in the absence of the Maml1 gene. Since Maml1(-/-) mice suffered perinatal lethality, hematopoietic chimeras were generated with Maml1(-/-), Maml1(+/-), or wild-type fetal liver progenitors. Maml1 deficiency minimally affected T-cell development, but was required for the development of MZB cells, similar to the phenotype of Notch2 deficiency. Moreover, the number of MZB cells correlated with Maml1 gene dosage. Since all 3 Maml genes were expressed in MZB cells and their precursors, these results suggest that Maml1 is specifically required for Notch2 signaling in MZB cells. C1 Univ Florida, Shands Canc Ctr, Dept Microbiol & Mol Genet, Canc & Genet Res Complex, Gainesville, FL 32610 USA. Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. Univ Penn, Sch Med, Div Hematol Oncol, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Inst Med & Engn, Philadelphia, PA 19104 USA. RP Wu, L (reprint author), Univ Florida, Shands Canc Ctr, Dept Microbiol & Mol Genet, Canc & Genet Res Complex, Rm 362,1376 Mowry Rd, Gainesville, FL 32610 USA. EM lzwu@ufl.edu FU NCI NIH HHS [R01 CA036167, R01 CA097148, R01CA036167, R01CA097148]; NIAID NIH HHS [R01AI047833, R01 AI047833] NR 30 TC 25 Z9 26 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 2007 VL 110 IS 10 BP 3618 EP 3623 DI 10.1182/blood-2007-06-097030 PG 6 WC Hematology SC Hematology GA 231KS UT WOS:000250946300027 PM 17699740 ER PT J AU Bahary, N Goishi, K Stuckenholz, C Weber, G LeBlanc, J Schafer, CA Berman, SS Klagsbrun, M Zon, LI AF Bahary, Nathan Goishi, Katsutoshi Stuckenholz, Carsten Weber, Gerhard LeBlanc, Jocelyn Schafer, Christopher A. Berman, Sarah S. Klagsbrun, Michael Zon, Leonard I. TI Duplicate VegfA genes and orthologues of the KDR receptor tyrosine kinase family mediate vascular development in the zebrafish SO BLOOD LA English DT Article ID ENDOTHELIAL-GROWTH-FACTOR; BLOOD-VESSEL DEVELOPMENT; FOCAL ADHESION KINASE; TARGETED INACTIVATION; MULTIPLE ROLES; ANGIOGENESIS; MICE; VASCULOGENESIS; EXPRESSION; ISOFORMS AB Vascular endothelial growth factor A (VEGFA) and the type III receptor tyrosine kinase receptors (RTKs) are both required for the differentiation of endothelial cells (vasculogenesis) and for the sprouting of new capillaries (anglogenesis). We have isolated a duplicated zebrafish VegfA locus, termed VegfAb, and a duplicate RTK locus with homology to KDR/FLK1 (named Kdrb). Morpholinodisrupted VegfAb embryos develop a normal circulatory system until approximately 2 to 3 days after fertilization (dpf), when defects in angiogenesis permit blood to extravasate into many tissues. Unlike the VegfAa(121) and VegfAa(165) isoforms, the VegfAb isoforms VegfAb(171) and VegfAb(210) are not normally secreted when expressed in mammalian tissue culture cells. The Kdrb locus encodes a 1361-amino acid transmembrane receptor with strong homology to mammalian KDR. Combined knockdown of both RTKs leads to defects in vascular development, suggesting that they cooperate in mediating! the vascular effects of VegfA in zebrafish development. Both VegfAa and VegfAb can individually bind and promote phosphorylation of both Flk1 (Kdra) and Kdrb, proteins in vitro. Taken together, our data support a model in the zebrafish, in which duplicated VegfA and multiple type III RTKs mediate vascular development. C1 Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Sch Med, Dept Mol Genet & Biochem, Pittsburgh, PA 15260 USA. Childrens Hosp, Vasc Biol Program, Boston, MA 02115 USA. Childrens Hosp Boston, Howard Hughes Med Inst, Boston, MA USA. Childrens Hosp Boston, Stem Cell Program, Boston, MA USA. Childrens Hosp Boston, Div Hematol Oncol, Boston, MA USA. Dana Faber Canc Inst, Boston, MA USA. RP Bahary, N (reprint author), Univ Pittsburgh, Sch Med, Dept Med, 3501 5th Ave,5058 BST3, Pittsburgh, PA 15260 USA. EM bahary@pitt.edu FU NHLBI NIH HHS [K08 HL03777]; PHS HHS [NIH/NCI 45548] NR 60 TC 62 Z9 66 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 2007 VL 110 IS 10 BP 3627 EP 3636 DI 10.1182/blood-2006-04-016378 PG 10 WC Hematology SC Hematology GA 231KS UT WOS:000250946300029 PM 17698971 ER PT J AU Vallet, S Raje, N Ishitsuka, K Hideshima, T Podar, K Chhetri, S Pozzi, S Breitkreutz, I Kiziltepe, T Yasui, H Ocio, EM Shiraishi, N Jin, J Okawa, Y Ikeda, H Mukherjee, S Vaghela, N Cirstea, D Ladetto, M Boccadoro, M Anderson, KC AF Vallet, Sonia Raje, Noopur Ishitsuka, Kenji Hideshima, Teru Podar, Klaus Chhetri, Shweta Pozzi, Samantha Breitkreutz, Iris Kiziltepe, Tanyel Yasui, Hiroshi Ocio, Enrique M. Shiraishi, Norihiko Jin, Janice Okawa, Yutaka Ikeda, Hiroshi Mukherjee, Siddhartha Vaghela, Nileshwari Cirstea, Diana Ladetto, Marco Boccadoro, Mario Anderson, Kenneth C. TI MLN3897, a novel CCR1 inhibitor, impairs osteoclastogenesis and inhibits the interaction of multiple myeloma cells and osteoclasts SO BLOOD LA English DT Article ID MACROPHAGE INFLAMMATORY PROTEIN-1-ALPHA; KAPPA-B LIGAND; CHEMOKINE RECEPTORS; BONE-DISEASE; OSTEOLYTIC LESIONS; INTEGRIN AVIDITY; PROTEIN 1-ALPHA; KEY REGULATOR; IN-VITRO; C-FOS AB The interaction between osteoclasts (OCs) and multiple myeloma (MM) cells plays a key role in the pathogenesis of MM-related osteolytic bone disease (01313). MM cells promote OC formation and, in turn, OCs enhance MM cell proliferation. Chemokines are mediators of MM effects on bone and vice versa; in particular, CCL3 enhances OC formation and promotes MM cell migration and survival. Here, we characterize the effects of MLN3897, a novel specific antagonist of the chemokine receptor CCR1, on both OC formation and OC-MM cell interactions. MLN3897 demonstrates significant impairment of OC formation (by 40%) and function (by 70%), associated with decreased precursor cell multinucleation and down-regulation of c-fos signaling. OCs secrete high levels of CCL3, which triggers MM cell migration; conversely, MLN3897 abrogates its effects by inhibiting Akt signaling. Moreover, MM cell-to-OC adhesion was abrogated by MLN3897, thereby inhibiting MM cell survival and proliferation. Our results therefore show novel biologic sequelae of CCL3 and its inhibition in both osteoclastogenesis and MM cell growth, providing the preclinical rationale for clinical trials of MLN3897 to treat OBD in MM. C1 Harvard Univ, Sch Med, Jerome Lipper Multiple Meyloma Dis Ctr, Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Turin, Div Hematol, Turin, Italy. Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA. RP Anderson, KC (reprint author), Harvard Univ, Sch Med, Jerome Lipper Multiple Meyloma Dis Ctr, Dana Farber Canc Inst, Mayer 557,44 Binney St, Boston, MA 02115 USA. EM kenneth_anderson@dfci.harvard.edu RI Pozzi, Samantha/A-7617-2012; OI Pozzi, Samantha/0000-0001-7917-1774; LADETTO, Marco/0000-0002-8283-2681 FU NCI NIH HHS [IP50 CA10070-01, R0-1 CA 50947, R01 CA050947]; PHS HHS [P0-1 78378] NR 39 TC 82 Z9 84 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 2007 VL 110 IS 10 BP 3744 EP 3752 DI 10.1182/blood-2007-05-093294 PG 9 WC Hematology SC Hematology GA 231KS UT WOS:000250946300043 PM 17715391 ER PT J AU Mok, W Boucher, Y Jain, RK AF Mok, Wison Boucher, Yves Jain, Rakesh K. TI Matrix metalloproteinases-1 and -8 improve the distribution and efficacy of an oncolytic virus SO CANCER RESEARCH LA English DT Article ID GENE-EXPRESSION; TUMORS; DIFFUSION; COLLAGEN; MACROMOLECULES; CONVECTION; TRANSPORT; DELIVERY; TISSUES; CANCER AB Oncolytic viral vectors show enormous potential for the treatment of many solid tumors. However, these vectors often suffer from insufficient delivery within tumors, which limits their efficacy in both preclinical and clinical settings. We have previously shown that tumor collagen can significantly hinder diffusion, and that its degradation can enhance the distribution and efficacy of an oncolytic herpes simplex virus (HSV) vector. Here, we identify two members of the matrix metalloproteinase (MMP) family of enzymes, MMP-1 and MMP-8, which can modulate the tumor matrix and enhance HSV delivery and efficacy. We show that overexpression of MMP-1 and MMP-8 in the human soft tissue sarcoma HSTS26T leads to a significant depletion of tumor-sulfated glycosaminoglycans. This increases the hydraulic conductivity of these tumors and enhances the flow of virus during injection. In control tumors, injected virus accumulates primarily in the periphery of the tumor. In contrast, we observed a more widespread distribution of virus around the injection site in MMP-1- and MMP-8-expressing tumors. Due to this enhanced vector delivery, MMP-expressing tumors respond significantly better to oncolytic HSV treatment than control tumors. Thus, these findings introduce a new approach to improve the delivery and efficacy of oncolytic viral vectors: modulation of tumor glycosaminoglycans to enhance convection. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, E L Steele Lab,Dept Radiat Oncol, Boston, MA 02114 USA. MIT, Dept Chem Engn, Cambridge, MA 02139 USA. RP Jain, RK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, E L Steele Lab,Dept Radiat Oncol, 100 Blossom St,Cox 7, Boston, MA 02114 USA. EM jajn@steele.mgh.harvard.edu FU NCI NIH HHS [P01CA80124, R01CA98706, R01CA85140] NR 22 TC 60 Z9 62 U1 1 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 2007 VL 67 IS 22 BP 10664 EP 10668 DI 10.1158/0008-5472.CAN-07-3107 PG 5 WC Oncology SC Oncology GA 232UA UT WOS:000251044000007 PM 18006807 ER PT J AU Martin, ES Tonon, G Sinha, R Xiao, YH Feng, B Kimmelman, AC Protopopov, A Ivanova, E Brennan, C Montgomery, K Kucherlapati, R Bailey, G Redston, M Chin, L DePinho, RA AF Martin, Eric S. Tonon, Giovanni Sinha, Raktim Xiao, Yonghong Feng, Bin Kimmelman, Alec C. Protopopov, Alexei Ivanova, Elena Brennan, Cameron Montgomery, Kate Kucherlapati, Raju Bailey, Gerald Redston, Mark Chin, Lynda DePinho, Ronald A. TI Common and distinct genomic events in sporadic colorectal cancer and diverse cancer types SO CANCER RESEARCH LA English DT Article ID HIGH-RESOLUTION ANALYSIS; CHROMOSOMAL GAINS; MICROSATELLITE INSTABILITY; HYBRIDIZATION ANALYSIS; GENETIC INSTABILITY; COLON-CANCER; TUMORS; MUTATIONS; CELLS; TUMORIGENESIS AB Colorectal cancer (CRC) is a major cause of cancer morbidity and mortality, and elucidation of its underlying genetics has advanced diagnostic screening, early detection, and treatment. Because CRC genomes are characterized by numerous non-random chromosomal structural alterations, we sought to delimit regions of recurrent amplifications and deletions in a collection of 42 primary specimens and 37 tumor cell lines derived from chromosomal instability neoplasia and microsatellite instability neoplasia CRC subtypes and to compare the pattern of genomic aberrations in CRC with those in other cancers. Application of oligomer-based array-comparative genome hybridization and custom analytic tools identified 50 minimal common regions (MCRs) of copy number alterations, 28 amplifications, and 22 deletions. Fifteen were highly recurrent and focal (<12 genes) MCRs, five of them harboring known CRC genes including EGFR and MYC with the remaining 10 containing a total of 65 resident genes with established links to cancer. Furthermore, comparisons of these delimited genomic profiles revealed that 22 of the 50 CRC MCRs are also present in lung cancer, glioblastoma, and/or multiple myeloma. Among 22 shared MCRs, nine do not contain genes previously shown genetically altered in cancer, whereas the remaining 13 harbor 35 known cancer genes, of which only 14 have been linked to CRC pathogenesis. Together, these observations point to the existence of many yet-to-be discovered cancer genes driving CRC development, as well as other human cancers, and show the utility of high-resolution copy number analysis in the identification of genetic events common and specific to the development of various tumor types. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Belfer Inst Innovat Canc Sci,Ctr Appl Canc Sci, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet & Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Harvard Radiat Oncol Program, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Partners Ctr Genet & Genom, Boston, MA USA. Mem Sloan Kettering Canc Ctr, Dept Neurosurg, Neurosurg Serv, Weill Cornell Med Coll, New York, NY 10021 USA. RP DePinho, RA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Belfer Inst Innovat Canc Sci,Ctr Appl Canc Sci, 44 Binney St,M413, Boston, MA 02115 USA. EM lynda_chin@dfci.harvard.edu; ron_depinho@dfci.harvard.edu OI Brennan, Cameron/0000-0003-4064-8891 FU NCI NIH HHS [P50 CA127003-01, R01 CA099041, 5T32CA09361, R01 CA93947, R01CA84628, U01 CA84313] NR 50 TC 48 Z9 48 U1 1 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 2007 VL 67 IS 22 BP 10736 EP 10743 DI 10.1158/0008-5472.CAN-07-2742 PG 8 WC Oncology SC Oncology GA 232UA UT WOS:000251044000016 PM 18006816 ER PT J AU Trent, S Yang, CW Li, CQ Lynch, M Schmidt, EV AF Trent, Sally Yang, Chuanwei Li, Cuiqi Lynch, Mary Schmidt, Emmett V. TI Heat shock protein B8, a cyclin-dependent kinase-independent cyclin d1 target gene, contributes to its effects on radiation sensitivity SO CANCER RESEARCH LA English DT Article ID ESTROGEN-RECEPTOR-ALPHA; INVASIVE BREAST-CANCER; MITOCHONDRIAL-FUNCTION; EXPRESSION PROFILES; INDUCED APOPTOSIS; TOTAL MASTECTOMY; PROGNOSTIC VALUE; POOR-PROGNOSIS; FOLLOW-UP; OVEREXPRESSION AB Overexpression of cyclin D1 is associated with many cancers, and its overexpression is especially associated with a poor prognosis in breast cancer. Paradoxically, cyclin D1 is known to enhance radiation sensitivity, a finding that has not yet been therapeutically exploited. Proposed cyclin DI functions that could be involved in this effect include cyclin-dependent kinase (CDK)-dependent phosphorylation of retinoblastoma. gene product (pRb), titration of p21/p27 complexes, and less well-characterized effects on gene expression. In this report, we sought to clarify the functions of cyclin D1 that might con tribute to enhanced radiation sensitivity. Breast cancer cells stably overexpressing a cyclin D1 mutant (KE) that cannot interact with its CDK partners to phosphorylate pRb were as radiation sensitive as those expressing wild-type D1. Although cyclin D1 has been proposed to affect radiation sensitivity through interactions with p21, a cyclin D1 mutant defective for p21 interactions also increased radiation sensitivity. Cyclin D1 overexpression is generally confined to hormone receptor-positive breast cancers, wherein standard therapies include both radiation and hormonal therapies. Among several proposed CDK-independent cyclin D1 targets, we have identified heat shock protein B8 (HSPB8) as a target particularly associated with cyclin D1 and ER-positive tumors. We therefore evaluated its potential contribution to radiation sensitivity. Overexpression of HSPB8 markedly increased radiation sensitivity, and HSPB8 small interfering RNA blocked cyclin D1's enhancement of radiation sensitivity. Taken together, our results show that some of cyclin D1's effects on radiation sensitivity are CDK and p21 independent and identify HSPB8 as a candidate CDK-independent cyclin D1 target that can mediate its effects. C1 Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Canc Res Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Serv Pediat, Boston, MA 02114 USA. Churchill Hosp, Dept Radiotherapy, Oxford Canc Ctr, Oxford OX3 7LJ, England. RP Schmidt, EV (reprint author), Harvard Univ, Massachusetts Gen Hosp, Ctr Canc, Canc Res Ctr, 55 Fruit St,GRJ 904, Boston, MA 02114 USA. EM schmidt@helix.mgh.harvard.edu FU NCI NIH HHS [P50 CA89393, R01 CA112021, R01 CA69069] NR 57 TC 13 Z9 13 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 2007 VL 67 IS 22 BP 10774 EP 10781 DI 10.1158/0008-5472.CAN-07-1475 PG 8 WC Oncology SC Oncology GA 232UA UT WOS:000251044000021 PM 18006821 ER PT J AU Goulart, BHL Clark, JW Pien, HH Roberts, TG Finkelstein, SN Chabner, BA AF Goulart, Bernardo H. L. Clark, Jeffrey W. Pien, Homer H. Roberts, Thomas G. Finkelstein, Stan N. Chabner, Bruce A. TI Trends in the use and role of biomarkers in phase I oncology trials SO CLINICAL CANCER RESEARCH LA English DT Article ID GASTROINTESTINAL STROMAL TUMOR; SURROGATE END-POINTS; NONCYTOTOXIC AGENTS; CANCER-RESEARCH; DRUG; INHIBITOR; THERAPY; GROWTH AB Purpose: There has been interest in using biomarkers that aid the evaluation of new anticancer agents. We evaluated trends in the use of biomarkers and their contribution to the main goals of phase I trials. Experimental Design: We did a systematic review of abstracts submitted to the American Society of Clinical Oncology annual meeting from 1991 to 2002 and the publications related to these abstracts. We analyzed the use of biomarkers and their contribution to published phase I trials. Results: Twenty percent of American Society of Clinical Oncology phase I abstracts (503 of 2458) from 1991 to 2002 included biomarkers. This proportion increased over time (14% in 1991 compared with 26% in 2002; P < 0.02). Independent predictors of the use of biomarkers included National Cancer Institute sponsorship, submission in the time period of 1999 to 2002, adult population, and drug family (biological agents). Biomarkers supported dose selection for phase II studies in 11 of 87 of the trials (13%) emanating from these abstracts. However, the primary determinants of phase 11 dose and schedule were toxicity and/or efficacy in all but one of these 87 trials (1%). Biomarker studies provided evidence supporting the proposed mechanism of action in 34 of 87 of the published trials (39%). Conclusions: The use of biomarkers in phase I trials has increased over the period from 1991 to 2002. To date, biomarker utilization has made a limited and primarily supportive contribution to dose selection, the primary end point of phase I studies. Additional studies are needed to determine what type of biomarker information is most valuable to evaluate in phase I trials. C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. Harvard Univ, Dana Farber Harvard Canc Ctr, Sch Med, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Ctr Biomarkers Imaging, Dept Radiol, Boston, MA 02114 USA. Noonday Asset Management, Charlotte, NC USA. MIT, Program Pharmaceut Ind, Cambridge, MA 02139 USA. RP Goulart, BHL (reprint author), 4735 Ravenna Ave,NE Apartment 1, Seattle, WA 98105 USA. EM bhgoulart@hotmail.com NR 24 TC 61 Z9 61 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 2007 VL 13 IS 22 BP 6719 EP 6726 DI 10.1158/1078-0432.CCR-06-2860 PN 1 PG 8 WC Oncology SC Oncology GA 235AY UT WOS:000251207100024 PM 18006773 ER PT J AU McGovern, BH Birch, C Zaman, MT Bica, I Stone, D Quirk, JR Davis, B Zachary, K Basgoz, N Graeme-Cook, F Gandhi, RT AF McGovern, Barbara H. Birch, Christopher Zaman, M. Tauheed Bica, Ioana Stone, David Quirk, James R. Davis, Benjamin Zachary, Kimon Basgoz, Nesli Graeme-Cook, Fiona Gandhi, Rajesh T. TI Managing symptomatic drug-induced liver injury in HIV-hepatitis C virus-coinfected patients: A role for interferon SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ALPHA-2A PLUS RIBAVIRIN; NECROSIS-FACTOR-ALPHA; ANTIRETROVIRAL THERAPY; INFECTED PATIENTS; HISTOLOGICAL RESPONSE; GENE-EXPRESSION; B-VIRUS; HEPATOTOXICITY; DISEASE AB Background. Human immunodeficiency virus (HIV)-infected patients with hepatitis C virus (HCV) coinfection are at increased risk for drug-induced liver injury (DILI) compared with patients with HIV infection alone. The mechanism underlying this observation is unknown. We hypothesized that interferon (IFN) would induce biochemical improvement through its anti-inflammatory properties and thereby facilitate the reintroduction of antiretroviral therapy (ART) in patients with DILI. Methods. Patients with symptomatic DILI were referred for evaluation; biopsy of a liver sample was performed for all patients, except 1 with clinical cirrhosis. Results. Twelve patients with acquired immunodeficiency syndrome and symptomatic grade 3/4 hepatotoxicity received treatment with IFN and ribavirin (RBV). Seven of these patients had a history of recurrent DILI. The mean baseline CD4(+) T cell counts and HIV RNA levels were 124 cells/mm(3) and 115,369 copies/mL, respectively. Biopsies of liver samples demonstrated significant necroinflammation (mean grade, 10.3) and fibrosis (mean stage, 2.9). Three patients continued to receive ART when they began treatment with IFN-RBV; 9 reinitiated ART within an average of 12 weeks (range, 4-20 weeks) of HCV treatment initiation. All patients attained marked improvement in aminotransferases and continued to receive ART treatment during a mean follow-up regimen of 26.5 months, with subsequent virologic suppression and immunologic reconstitution (mean CD4(+) cell count increase, 251/mm(3)). However, only 1 patient maintained HCV suppression after completion of treatment with IFN-RBV. Conclusions. In patients with symptomatic DILI, treatment with IFN-ribavirin (RBV) led to decreases in aminotransferase levels, which enabled the reinitiation of ART. The beneficial effects of IFN-based therapy may be modulated through the suppression of proinflammatory cytokines, even in virologic nonresponders. Herein, we propose a novel mechanism for DILI, whereby HCV- and HIV-associated inflammatory mediators induce liver injury synergistically. C1 Tufts Univ, Sch Med, Lemuel Shattuck Hosp, HIV HCV Coinfect Clin, Boston, MA 02130 USA. Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Boston Med Ctr, Boston, MA USA. RP McGovern, BH (reprint author), Tufts Univ, Sch Med, Lemuel Shattuck Hosp, HIV HCV Coinfect Clin, Jamaica Pl, Boston, MA 02130 USA. EM bmcgovern@tufts-nemc.org NR 54 TC 2 Z9 2 U1 0 U2 0 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 2007 VL 45 IS 10 BP 1386 EP 1392 DI 10.1086/522174 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 222RY UT WOS:000250315900023 PM 17968840 ER PT J AU Thompson, GR Lawrence, VA Crawford, GE AF Thompson, George R., III Lawrence, Valerie A. Crawford, George E. TI HIV infection increases the risk of heparin-induced thrombocytopenia SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material ID HUMAN-IMMUNODEFICIENCY-VIRUS; AUTOIMMUNITY; AUTOANTIBODIES; HEPATITIS; AIDS AB The incidence of heparin-induced thrombocytopenia in human immunodeficiency virus (HIV)-infected inpatients was compared with that in a control group that was not known to be infected with HIV in a retrospective cohort study. HIV-infected patients receiving heparin therapy, especially unfractionated heparin therapy, were at increased risk of developing heparin-induced thrombocytopenia, compared with HIV-uninfected patients. C1 Univ Texas, Hlth Sci Ctr, Div Infect Dis, Dept Internal Med, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Div Gen Med, Dept Med, San Antonio, TX 78229 USA. RP Thompson, GR (reprint author), Univ Texas, Hlth Sci Ctr, Div Infect Dis, Dept Internal Med, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM thompsong2@uthscsa.edu NR 22 TC 8 Z9 8 U1 0 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 2007 VL 45 IS 10 BP 1393 EP 1396 DI 10.1086/522761 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 222RY UT WOS:000250315900024 PM 17968841 ER PT J AU Samuelson, AV Carr, CE Ruvkun, G AF Samuelson, Andrew V. Carr, Christopher E. Ruvkun, Gary TI Gene activities that mediate increased life span of C. elegans insulin-like signaling mutants SO GENES & DEVELOPMENT LA English DT Article DE aging; endocytosis; insulin; daf-2; C. elegans; RNAi ID HEAT-SHOCK FACTOR; AGE-RELATED-CHANGES; CAENORHABDITIS-ELEGANS; OXIDATIVE STRESS; PHOSPHOINOSITIDE PHOSPHATASE; CELL-FUNCTION; DAF-16; LONGEVITY; RECEPTOR; PROTEIN AB Genetic and RNA interference (RNAi) screens for life span regulatory genes have revealed that the daf-2 insulin-like signaling pathway plays a major role in Caenorhabditis elegans longevity. This pathway converges on the DAF-16 transcription factor and may regulate life span by controlling the expression of a large number of genes, including free-radical detoxifying genes, stress resistance genes, and pathogen resistance genes. We conducted a genome-wide RNAi screen to identify genes necessary for the extended life span of daf-2 mutants and identified similar to 200 gene inactivations that shorten daf-2 life span. Some of these gene inactivations dramatically shorten daf-2 mutant life span but less dramatically shorten daf-2; daf-16 mutant or wild-type life span. Molecular and behavioral markers for normal aging and for extended life span in low insulin/IGF1 (insulin-like growth factor 1) signaling were assayed to distinguish accelerated aging from general sickness and to examine age-related phenotypes. Detailed demographic analysis, molecular markers of aging, and insulin signaling mutant test strains were used to filter progeric gene inactivations for specific acceleration of aging. Highly represented in the genes that mediate life span extension in the daf-2 mutant are components of endocytotic trafficking of membrane proteins to lysosomes. These gene inactivations disrupt the increased expression of the DAF-16 downstream gene superoxide dismutase sod-3 in a daf-2 mutant, suggesting trafficking between the insulin-like receptor and DAF-16. The activities of these genes may normally decline during aging. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. MIT, Dept Earth Atmospher & Planetary Sci, Cambridge, MA 02139 USA. RP Ruvkun, G (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM ruvkun@molbio.mgh.harvard.edu OI Carr, Christopher/0000-0002-7946-5622 FU NIA NIH HHS [5 R01 AG16636] NR 65 TC 86 Z9 107 U1 1 U2 11 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD NOV 15 PY 2007 VL 21 IS 22 BP 2976 EP 2994 DI 10.1101/gad.1588907 PG 19 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 231RH UT WOS:000250966200013 PM 18006689 ER PT J AU Hamshere, ML Holmans, PA Avramopoulos, D Bassett, SS Blacker, D Bertram, L Wiener, H Rochberg, N Tanzi, RE Myers, A Vrieze, FWD Go, R Fallin, D Lovestone, S Hardy, J Goate, A O'Donovan, M Williams, J Owen, MJ AF Hamshere, Marian L. Holmans, Peter A. Avramopoulos, Dimitrios Bassett, Susan S. Blacker, Deborah Bertram, Lars Wiener, Howard Rochberg, Nan Tanzi, Rudolph E. Myers, Amanda Vrieze, Fabienne Wavrant-De Go, Rodney Fallin, Daniele Lovestone, Simon Hardy, John Goate, Alison O'Donovan, Michael Williams, Julie Owen, Michael J. TI Genome-wide linkage analysis of 723 affected relative pairs with late-onset Alzheimer's disease SO HUMAN MOLECULAR GENETICS LA English DT Article ID PARENT-OF-ORIGIN; APOLIPOPROTEIN-E; COMPLEX TRAITS; LOCUS; GENE; CHROMOSOME-10; ASSOCIATION; COVARIATE; SCREEN; AGE AB Previous attempts to identify genetic loci conferring risk for late-onset Alzheimer's disease (LOAD) through linkage analysis have observed some regions of linkage in common. However, due to the sometimes-considerable overlap between the samples, some of these reports cannot be considered to be independent replications. In order to assess the strength of the evidence for linkage and to obtain the best indication of the location of susceptibility genes, we have amalgamated three large samples to give a total of 723 affected relative pairs (ARPs). Multipoint, model-free ARP linkage analysis was performed. Genome-wide significant evidence for linkage was observed on 10q21.2 (LOD = 3.3) and genome-wide suggestive evidence was observed on 9q22.33 (LOD = 2.5) and 19q13.32 (LOD = 2.0). One further region on 9p21.3 was identified with an LOD score > 1. We observe no evidence to suggest that more than one locus is responsible for the linkage to 10q21.2, although this linked region may harbour more than one susceptibility gene. Evidence of allele-sharing heterogeneity between the original collection sites was observed on chromosome 9 but not on chromosome 10 or 19. Evidence for an interaction was observed between loci on chromosomes 10 and 19. Where samples overlapped, the genotyping consistency was high, estimated to average at 97.3%. Our large-scale linkage analysis consolidates clear evidence for a susceptibility locus for LOAD on 10q21.2. C1 Cardiff Univ, Sch Med, Dept Med Psychol, Cardiff CF14 4XN, S Glam, Wales. Cardiff Univ, Biostat & Bioinformat Unit, Sch Med, Cardiff CF14 4XN, S Glam, Wales. Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat,Gerontol Res Unit, Charlestown, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Genet & Aging Res Unit, Charlestown, MA 02129 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Univ Alabama, Dept Epidemiol, Birmingham, AL USA. Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. Univ Miami, Miller Sch Med, Dept Psychiat & Behav Sci, Coral Gables, FL 33124 USA. NIA, Neurogenet Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. Kings Coll London, Inst Psychiat, MRC, Ctr Neurodegenerat Res, London SE5 8AF, England. UCL, Dept Mol Neurosci, Inst Neurol, London WC1N 3BG, England. UCL, Reta Lila Weston Labs, Inst Neurol, London WC1N 3BG, England. RP Owen, MJ (reprint author), Cardiff Univ, Sch Med, Dept Med Psychol, Heath Pk, Cardiff CF14 4XN, S Glam, Wales. EM owenmj@cardiff.ac.uk RI Lovestone, Simon/E-8725-2010; Myers, Amanda/B-1796-2010; turton, miranda/F-4682-2011; Hardy, John/C-2451-2009; Avramopoulos, Dimitrios/J-4392-2012; Holmans, Peter/F-4518-2015; Bertram, Lars/K-3889-2015; OI Myers, Amanda/0000-0002-3100-9396; Holmans, Peter/0000-0003-0870-9412; Bertram, Lars/0000-0002-0108-124X; O'Donovan, Michael/0000-0001-7073-2379 FU Medical Research Council [G0300429, G0701075, G9810900]; NIA NIH HHS [U24 AG021886]; Parkinson's UK [G-0907] NR 46 TC 32 Z9 32 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD NOV 15 PY 2007 VL 16 IS 22 BP 2703 EP 2712 DI 10.1093/hmg/ddm224 PG 10 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 227SZ UT WOS:000250679400006 PM 17725986 ER PT J AU Hayman, JA Abrahamse, PH Lakhani, I Earle, CC Katz, SJ AF Hayman, James A. Abrahamse, Paul H. Lakhani, Indu Earle, Craig C. Katz, Steven J. TI Use of palliative radiotherapy among patients with metastatic non-small-cell lung cancer SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT 39th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 31-JUN 03, 2003 CL CHICAGO, IL SP Amer Soc Clin Oncol DE non-small-cell lung cancer; palliation; radiotherapy; utilization ID BREAST-CANCER; RADIATION-THERAPY; PROSTATE-CANCER; UNITED-STATES; TREATMENT PATTERNS; COMORBIDITY INDEX; INITIAL TREATMENT; MEDICARE PATIENTS; OLDER WOMEN; POPULATION AB Purpose: Radiotherapy (RT) is known to effectively palliate many symptoms of patients with metastatic non-small-cell lung cancer (NSCLC). Anecdotally, RT is believed to be commonly used in this setting, but limited population-based data are available. The objective of this study was to examine the utilization patterns of palliative RT among elderly patients with Stage IV NSCLC and, in particular, to identify factors associated with its use. Methods and Materials: A retrospective population-based cohort study was performed using linked Surveillance, Epidemiology and End Results (SEER)-Medicare data to identify 11,084 Medicare beneficiaries aged >= 65 years who presented with Stage IV NSCLC in the 11 SEER regions between 1991 and 1996. The primary outcome was receipt of RT. Logistic regression analysis was used to identify factors associated with receipt of RT. Results: A total of 58% of these patients received RT, with its use decreasing over time (p = 0.01). Increasing age was negatively associated with receipt of treatment (p < 0.001), as was increasing comorbidities (p < 0.001). Factors positively associated with the receipt of RT included income (p = 0.001), hospitalization (p < 0.001), and treatment with chemotherapy (p < 0.001). Although the use varied across the SEER regions (p = 0.001), gender, race/ethnicity, and distance to the nearest RT facility were not associated with treatment. Conclusions: Elderly patients with metastatic NSCLC frequently receive palliative RT, but its use varies, especially with age and receipt of chemotherapy. Additional research is needed to determine whether this variability reflects good quality care. (c) 2007 Elsevier Inc. C1 Univ Michigan, Med Ctr, Dept Radiat Oncol, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Internal Med, Div Gen Med, Ann Arbor, MI 48109 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Hayman, JA (reprint author), Univ Michigan, Med Ctr, Dept Radiat Oncol, UH B2C490,1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. EM hayman@urnich.edu FU NCI NIH HHS [R21 CA89490] NR 43 TC 24 Z9 24 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD NOV 15 PY 2007 VL 69 IS 4 BP 1001 EP 1007 DI 10.1016/j.ijrobp.2007.06.059 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 229FQ UT WOS:000250788900005 PM 17689029 ER PT J AU Cormack, RA Holloway, CL O'Farrell, D Devlin, PM AF Cormack, Robert A. Holloway, Caroline L. O'Farrell, Desmond Devlin, Phillip M. TI Permanent planar iodine-125 implants: The dosimetric effect of geometric parameters for idealized source configurations SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE brachytherapy; planar implant; iodine-125; dosimetry ID INTERSTITIAL-BRACHYTHERAPY; RECOMMENDATIONS AB Purpose: To provide dosimetric information about permanent planar 1251 implants in a manner that is useful to the brachytherapist in the operative setting. Methods and Materials: Reference planar permanent implants were simulated for a variety of areas with sources placed uniformly on a 1-cm grid. Implants having variable source spacing and curvature were simulated and compared with the reference implants. Dosimetric measures were calculated at 0.5 and 1.0 cm from the implant plane. Results: A method for calculating dosimetric statistics for permanent implants ranging from 5 x 5 cult to 13 x 13 cm is presented. A formula to predict the reference source strength needed to achieve a desired dosimetric quantity is also presented. The effect of adjusting strand spacing to compensate for source activity is presented and is shown to be an effective means to adjust implants to use source strengths other than the reference strength. The effect of implant curvature compared with flat implants on dosimetric statistics is presented as a function of radius of curvature. Conclusions: The results presented in this work may be used to provide information about dose delivered from planar permanent implants. (c) 2007 Elsevier Inc. C1 Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, Div Brachytherapy, Boston, MA USA. BC Canc Agcy, Dept Radiat Oncol, Ctr So Interior, Kelowna, BC, Canada. RP Cormack, RA (reprint author), Brigham & Womens Hosp, Dept Radiat Oncol L2, 75 Francis St, Boston, MA 02215 USA. EM rcormack@troc.harvard.edu OI Cormack, Robert/0000-0001-5553-9984 NR 9 TC 3 Z9 3 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 2007 VL 69 IS 4 BP 1310 EP 1315 DI 10.1016/j.ijrobp.2007.07.2367 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 229FQ UT WOS:000250788900046 PM 17967321 ER PT J AU Frahm, N Kaufmann, DE Yusim, K Muldoon, M Kesmir, C Linde, CH Fischer, W Allen, TM Li, B McMahon, BH Faircloth, KL Hewitt, HS Mackey, EW Miura, T Khatri, A Wolinsky, S McMichael, A Funkhouser, RK Walker, BD Brander, C Korber, BT AF Frahm, Nicole Kaufmann, Daniel E. Yusim, Karina Muldoon, Mark Kesmir, Can Linde, Caitlyn H. Fischer, Will Allen, Todd M. Li, Bin McMahon, Ben H. Faircloth, Kellie L. Hewitt, Hannah S. Mackey, Elizabeth W. Miura, Toshiyuki Khatri, Ashok Wolinsky, Steven McMichael, Andrew Funkhouser, Robert K. Walker, Bruce D. Brander, Christian Korber, Bette T. TI Increased sequence diversity coverage improves detection of HIV-Specific T cell responses SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; IMMUNODOMINANT REGIONS; ENHANCED DETECTION; LYMPHOCYTE ESCAPE; TYPE-1 INFECTION; VACCINE DESIGN; VIRAL LOAD; SUBTYPE-C; SELECTION; TRANSMISSION AB The accurate identification of HIV-specific T cell responses is important for determining the relationship between immune response, viral control, and disease progression. HIV-specific immune responses are usually measured using peptide sets based on consensus sequences, which frequently miss responses to regions where test set and infecting virus differ. In this study, we report the design of a peptide test set with significantly increased coverage of HIV sequence diversity by including alternative amino acids at variable positions during the peptide synthesis step. In an IFN-gamma ELISpot assay, these "toggled" peptides detected HIV-specific CD4(+) and CD8(+) T cell responses of significantly higher breadth and magnitude than matched consensus peptides. The observed increases were explained by a closer match of the toggled peptides to the autologous viral sequence. Toggled peptides therefore afford a cost-effective and significantly more complete view of the host immune response to HIV and are directly applicable to other variable pathogens. C1 Los Alamos Natl Lab, Los Alamos, NM 87545 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, AIDS Res Ctr, Boston, MA 02129 USA. Univ Manchester, Sch Math, Manchester, Lancs, England. Tech Univ Denmark, Ctr Biol Sequence Anal, DK-2800 Lyngby, Denmark. Univ Utrecht, Utrecht, Netherlands. Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Northwestern Univ, Feinberg Sch Med, Dept Med, Chicago, IL 60611 USA. Northwestern Univ, Inter Inst Nanotechnol, Evanston, IL 60208 USA. Univ Oxford, John Radcliffe Hosp, MRC, Human Immunol Unit,Weatherall Inst Mol Med, Oxford OX3 9DU, England. Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. Santa Fe Inst, Santa Fe, NM 87501 USA. RP Korber, BT (reprint author), Los Alamos Natl Lab, MS K710,T-10, Los Alamos, NM 87545 USA. EM cbrander@partners.org; btk@lanl.gov RI Muldoon, Mark/C-7505-2009; Wolinsky, Steven/B-2893-2012; Fischer, Will/B-1323-2013; Allen, Todd/F-5473-2011; Kesmir, Can/B-9410-2011; OI Fischer, Will/0000-0003-4579-4062; Wolinsky, Steven/0000-0002-9625-6697; Korber, Bette/0000-0002-2026-5757 FU Medical Research Council [MC_U137884177]; NHLBI NIH HHS [R01 HL092565]; NIAID NIH HHS [AI-30024, N01-AI-15442, R01-AI-054178, R01-AI-067077, R21-AI-055421, R56-AI-071726] NR 38 TC 29 Z9 30 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 2007 VL 179 IS 10 BP 6638 EP 6650 PG 13 WC Immunology SC Immunology GA 229HA UT WOS:000250792700032 PM 17982054 ER PT J AU Roman, GC Reis, J Defer, GL Prockop, LD AF Roman, G. C. Reis, J. Defer, G. L. Prockop, L. D. TI Introduction to the special issue on environmental neurology SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Editorial Material C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX 78249 USA. Audie L Murphy Mem Vet Adm Med Ctr, Vet Adm, San Antonio, TX 78284 USA. Univ Strasbourg, Fac Med, Strasbourg, France. Univ Hosp, Neurol Serv, Caen, France. Univ S Florida, Coll Med, Dept Neurol, Tampa, FL USA. RP Roman, GC (reprint author), Univ Texas, Hlth Sci Ctr, 6900 North Loop 1604 W, San Antonio, TX 78249 USA. EM romang@uthscsa.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD NOV 15 PY 2007 VL 262 IS 1-2 BP 1 EP 1 DI 10.1016/j.jns.2007.06.015 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 221RL UT WOS:000250244900001 ER PT J AU Reis, J Roman, GC AF Reis, Jacques Roman, Gustavo C. TI Environmental neurology: A promising new field of practice and research SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Article; Proceedings Paper CT Meeting of the Environmental-Neurology-Club CY FEB 07, 2007 CL Metz, FRANCE SP French Soc Neurol, Univ Metz, Enviornm Neruol Res Grp, WFN, Environm Neurol Club DE environment; hazard; risk; adaptation; vulnerability; gene-environment ID ALZHEIMERS-DISEASE; MEDITERRANEAN DIET; OPTIC NEUROPATHY; HEALTH; RISK; GUAM; SCLEROSIS; EPIDEMIC; CASSAVA; BLOOD AB The environment has profound influences on human health. Environment is the combination of natural (physical, chemical, biological) and cultural (sociological) conditions in which living organisms, man in particular, develop. Adaptation is the human physiological response to external factors including mechanisms such as circadian rhythms (sleep and wakefulness), biorhythms, thermoregulation, and others to adjust to changes in natural conditions (night and day, cosmic rhythms, climatic changes). Man remains vulnerable due to a number of factors: genetic, physiological, age, sex, impaired reparative or protective mechanisms, or acquired factors (risky behaviors and lifestyle, nutritional habits). Hazard is the potential of a particular factor to have a negative impact on health. Risk is the probability of that hazard occurring; it defines and measures the predictability of that hazard. A number of environmental factors have a profound influence on the pathogenesis of neurological disorders. Environmental neurology follows the classical diagnostic precepts: from symptom to syndrome in the search for etiology and individualized treatment of the patient. It also utilizes principles of epidemiology and public health, toxicology and occupational medicine; i.e., an approach by "milieu" and by specific factors or "agents." Environmental neurology offers a promising new field of practice and research. (c) 2007 Elsevier B.V. All rights reserved. C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX 78249 USA. Audie Murphy Hosp, Vet Adm, San Antonio, TX 78284 USA. RP Roman, GC (reprint author), Univ Texas, Hlth Sci Ctr, San Antonio, TX 78249 USA. EM romang@uthscsa.edu NR 27 TC 3 Z9 3 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD NOV 15 PY 2007 VL 262 IS 1-2 BP 3 EP 6 DI 10.1016/j.jns.2007.06.017 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 221RL UT WOS:000250244900003 PM 17651758 ER PT J AU Roman, GC AF Roman, Gustavo C. TI Autism: Transient in utero hypothyroxinemia related to maternal flavonoid ingestion during pregnancy and to other environmental antithyroid agents SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Article; Proceedings Paper CT Meeting of the Environmental-Neurology-Club CY FEB 07, 2007 CL Metz, FRANCE SP French Soc Neurol, Univ Metz, Enviornm Neruol Res Grp, WFN, Environm Neurol Club DE autism; hypothyroxinemia; pregnancy; antithyroid agents; iodine; endemic cretinism; herbicides; neuronal migration; soy; mercury; polyphenols ID FETAL-BRAIN DEVELOPMENT; REELIN GENE ALLELES; THYROID-HORMONE; SPECTRUM DISORDERS; IODINE DEFICIENCY; UNITED-STATES; ORGANOCHLORINE COMPOUNDS; CHLORALKALI WORKERS; MERCURIC-CHLORIDE; ENDEMIC CRETINISM AB The incidence and prevalence of autism have increased during the past two decades. Despite comprehensive genetic studies the cause of autism remains unknown. This review emphasizes the potential importance of environmental factors in its causation. Alterations of cortical neuronal migration and cerebellar Purkinje cells have been observed in autism. Neuronal migration, via reelin regulation, requires triiodothyronine (T3) produced by deiodination of thyroxine (T4) by fetal brain deiodinases. Experimental animal models have shown that transient intrauterine deficits of thyroid hormones (as brief as 3 days) result in permanent alterations of cerebral cortical architecture reminiscent of those observed in brains of patients with autism. 1 postulate that early maternal hypothyroxinetnia resulting in low T3 in the fetal brain during the period of neuronal cell migration (weeks 8-12 of pregnancy) may produce morphological brain changes leading to autism. Insufficient dietary iodine intake and a number of environmental antithyroid and goitrogenic agents can affect maternal thyroid function during pregnancy. The most common causes could include inhibition of deiodinases D2 or D3 from maternal ingestion of dietary flavonoids or from antithyroid environmental contaminants. Some plant isoflavonoids have profound effects on thyroid hormones and on the hypothalamus-pituitary axis. Genistein and daidzein from soy (Glycine max) inhibit thyroperoxidase that catalyzes iodination and thyroid hormone biosynthesis. Other plants with hypothyroid effects include pearl millet (Pennisetum glaucum) and fonio millet (Digitaria exilis); thiocyanate is found in Brassicae plants including cabbage, cauliflower, kale, rutabaga, and kohlrabi, as well as in tropical plants such as cassava, lima beans, linseed, bamboo shoots, and sweet potatoes. Tobacco smoke is also a source of thiocyanate. Environmental contaminants interfere with thyroid function including 60% of all herbicides, in particular 2,4-dichlorophenoxyacetic acid (2,4-D), acetochlor, aminotriazole, atmitrole, bromoxynil, pendamethalin, mancozeb, and thioureas. Other antithyroid agents include polychlorinated biphenyls (PCBs), perchlorates, mercury, and coal derivatives such as resorcinol, phthalates, and anthracenes. A leading ecological study in Texas has correlated higher rates of autism in school districts affected by large environmental releases of mercury from industrial sources. Mercury is a well known antithyroid substance causing inhibition of deiodinases and thyroid peroxidase. The current surge of autism could be related to transient maternal hypothyroxinemia resulting from dietary and/or environmental exposure to antithyroid agents. Additional multidisciplinary epidemiological studies will be required to confirm this environmental hypothesis of autism. (c) 2007 Elsevier B.V All rights reserved. C1 Vet Adm Hosp, San Antonio, TX USA. RP Roman, GC (reprint author), Univ Texas, Hlth Sci Ctr, San Antonio, TX 78249 USA. EM romang@uthscsa.edu NR 143 TC 57 Z9 61 U1 3 U2 25 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD NOV 15 PY 2007 VL 262 IS 1-2 BP 15 EP 26 DI 10.1016/j.jns.2007.06.023 PG 12 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 221RL UT WOS:000250244900005 PM 17651757 ER PT J AU Bernal-Pacheco, O Roman, GC AF Bernal-Pacheco, Oscar Roman, Gustavo C. TI Environmental vascular risk factors: New perspectives for stroke prevention SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Article; Proceedings Paper CT Meeting of the Environmental-Neurology-Club CY FEB 07, 2007 CL Metz, FRANCE SP French Soc Neurol, Univ Metz, Enviornm Neruol Res Grp, WFN, Environm Neurol Club DE stroke; obesity; vascular risk factors; education; socioeconomic factors; sleep apnea; periodontal disease; diet ID OBSTRUCTIVE SLEEP-APNEA; CORONARY-HEART-DISEASE; C-REACTIVE PROTEIN; SYSTOLIC BLOOD-PRESSURE; 1ST ISCHEMIC-STROKE; OF-THE-LITERATURE; CARDIOVASCULAR-DISEASE; PERIODONTAL-DISEASE; METABOLIC SYNDROME; PHYSICAL-ACTIVITY AB Despite intensive evaluation of acute stroke patients, perhaps only half of the attributable stroke risk is usually identified. In addition to traditional and non-traditional vascular risk factors-including most recently homocysteine, inflammation, and alterations of coagulation-a number of environmental risk factors for stroke have been identified in the last decade. In this update we review the following: lower education and poor socioeconomic status (probable surrogates for exposure to traditional high-risk behaviors such as smoking, poor nutrition, lack of prenatal control, absence of preventive medical and dental care, and non-compliance of treatment of conditions such as hypertension); depression, stress and affective disorders; obstructive sleep apnea; passive smoking and environmental pollution; infections, in particular periodontal diseases that increase C-reactive protein (CRP); raised body mass index (obesity); exercise, and diet. The possible role of high-fructose corn syrup in the epidemic of obesity in the USA is reviewed. Protective diets include higher consumption of fish, olive oil, grains, fruits and vegetables (Mediterranean diet), as well as probiotic bacteria in yogurt and dairy products. Careful attention should be given to the patient's environment looking for modifiable factors. The effects of clean environmental air and water, adequate diet and appropriate nutrition, healthy teeth, exercise, and refreshing sleep in the prevention of stroke and cardiovascular disease appear to be quite compelling. Although some of these modifiable risk factors lack evidence-based information, judicious clinical sense should be used to counteract the potentially damaging effects of adverse environmental vascular risk factors. (c) 2007 Elsevier B.V. All rights reserved. C1 Univ Texas, Hlth Sci Ctr, San Antonio, TX 78249 USA. Vet Adm Hosp, San Antonio, TX USA. Cent Mil Hosp, Bogota, Colombia. RP Roman, GC (reprint author), Univ Texas, Hlth Sci Ctr, San Antonio, TX 78249 USA. EM romang@uthscsa.edu NR 161 TC 22 Z9 24 U1 5 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD NOV 15 PY 2007 VL 262 IS 1-2 BP 60 EP 70 DI 10.1016/j.jns.2007.06.026 PG 11 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 221RL UT WOS:000250244900010 PM 17655871 ER PT J AU Badgaiyan, RD Fischman, AJ Alpert, NM AF Badgaiyan, Rajendra D. Fischman, Alan J. Alpert, Nathaniel M. TI Striatal dopamine release in sequential learning SO NEUROIMAGE LA English DT Article ID POSITRON-EMISSION-TOMOGRAPHY; TONICALLY ACTIVE NEURONS; BASAL GANGLIA; MOTOR-SEQUENCE; RECEPTOR OCCUPANCY; PREFRONTAL CORTEX; PRIMATES STRIATUM; PET; ACTIVATION; TASK AB Sequential learning is an important aspect of cognitive processing. Neuropharmacological evidence acquired in laboratory animals suggests that striatal dopaminergic mechanisms may be important for processing of this form of learning. However, because experiments conducted on dopamine deficient patients have reported contradictory evidence, the role of dopamine and the striatum remains unclear in human sequential learning. We used a newly developed dynamic molecular imaging technique to determine whether striatal dopamine is released during performance of a sequential learning task. In this study we localized striatal regions where dopamine receptor ligand (C-11-raclopride) was displaced from receptor sites, during performance of a motor sequence learning (serial reaction time) task. The results suggest that the task induces release of endogenous dopamine in the posterior two-third of dorsomedial aspect of left putamen and the anterior part of the body of caudate bilaterally. The activations of the left putamen and the right caudate coincided with the activations observed earlier during performance of a motor planning task. Since these activations are associated with the selection and execution of a response, the activation in the left caudate, which was not observed in motor planning, is probably associated with the detection of a change in the 'context', and in the formulation of a new 'rule'. Thus, the results suggest that sequential learning involves two striatal dopaminergic mechanisms, one for the detection of a change in context, and the other for selection and execution of the response. (c) 2007 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Div Nucl Med White 427, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Shriners Hosp Children, Boston, MA 02114 USA. RP Badgaiyan, RD (reprint author), Massachusetts Gen Hosp, Div Nucl Med White 427, 55 Fruit St, Boston, MA 02114 USA. EM rajendra@wjh.harvard.edu FU NIMH NIH HHS [R21 MH073624-01, 1R21MH073624, R21 MH073624] NR 54 TC 62 Z9 62 U1 1 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD NOV 15 PY 2007 VL 38 IS 3 BP 549 EP 556 DI 10.1016/j.neuroimage.2007.07.052 PG 8 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 224FF UT WOS:000250432200015 PM 17888684 ER PT J AU Wiviott, SD Braunwald, E McCabe, CH Montalescot, G Ruzyllo, W Gottlieb, S Neumann, F Ardissino, D De Servi, S Murphy, SA Riesmeyer, J Weerakkody, G Gibson, CM Antman, EM AF Wiviott, Stephen D. Braunwald, Eugene McCabe, Carolyn H. Montalescot, Gilles Ruzyllo, Witold Gottlieb, Shmuel Neumann, Franz-Joseph Ardissino, Diego De Servi, Stefano Murphy, Sabina A. Riesmeyer, Jeffrey Weerakkody, Govinda Gibson, C. Michael Antman, Elliott M. CA TRITON TIMI 38 Investigators TI Prasugrel versus clopidogrel in patients with acute coronary syndromes SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ST-SEGMENT ELEVATION; PLATELET GLYCOPROTEIN IIB/IIIA; PLACEBO-CONTROLLED TRIAL; ACUTE MYOCARDIAL-INFARCTION; ORAL ANTIPLATELET THERAPY; HIGH-RISK PATIENTS; UNSTABLE ANGINA; STENT THROMBOSIS; ASPIRIN; INTERVENTION AB Background: Dual-antiplatelet therapy with aspirin and a thienopyridine is a cornerstone of treatment to prevent thrombotic complications of acute coronary syndromes and percutaneous coronary intervention. Methods: To compare prasugrel, a new thienopyridine, with clopidogrel, we randomly assigned 13,608 patients with moderate-to-high-risk acute coronary syndromes with scheduled percutaneous coronary intervention to receive prasugrel (a 60-mg loading dose and a 10-mg daily maintenance dose) or clopidogrel (a 300-mg loading dose and a 75-mg daily maintenance dose), for 6 to 15 months. The primary efficacy end point was death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The key safety end point was major bleeding. Results: The primary efficacy end point occurred in 12.1% of patients receiving clopidogrel and 9.9% of patients receiving prasugrel (hazard ratio for prasugrel vs. clopidogrel, 0.81; 95% confidence interval [CI], 0.73 to 0.90; P<0.001). We also found significant reductions in the prasugrel group in the rates of myocardial infarction (9.7% for clopidogrel vs. 7.4% for prasugrel; P<0.001), urgent target-vessel revascularization (3.7% vs. 2.5%; P<0.001), and stent thrombosis (2.4% vs. 1.1%; P<0.001). Major bleeding was observed in 2.4% of patients receiving prasugrel and in 1.8% of patients receiving clopidogrel (hazard ratio, 1.32; 95% CI, 1.03 to 1.68; P=0.03). Also greater in the prasugrel group was the rate of life-threatening bleeding (1.4% vs. 0.9%; P=0.01), including nonfatal bleeding (1.1% vs. 0.9%; hazard ratio, 1.25; P=0.23) and fatal bleeding (0.4% vs. 0.1%; P=0.002). Conclusions: In patients with acute coronary syndromes with scheduled percutaneous coronary intervention, prasugrel therapy was associated with significantly reduced rates of ischemic events, including stent thrombosis, but with an increased risk of major bleeding, including fatal bleeding. Overall mortality did not differ significantly between treatment groups. (ClinicalTrials.gov number, NCT00097591.). C1 Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Pitie Salpetriere Univ Hosp, Inst Cardiol, Paris, France. Pitie Salpetriere Univ Hosp, INSERM, U856, Paris, France. Inst Kardiol, Warsaw, Poland. Bikur Cholim Hosp, Jerusalem, Israel. Herz Zentrum Bad Krozingen, Bad Krozingen, Germany. Univ Parma, Azienda Osped, I-43100 Parma, Italy. Azienda Osped Civile Legano, Legnano, Italy. Eli Lilly Res Labs, Indianapolis, IN USA. RP Antman, EM (reprint author), Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc, 350 Longwood Ave,1st Fl, Boston, MA 02115 USA. EM eantman@rics.bwh.harvard.edu NR 44 TC 2815 Z9 2941 U1 11 U2 97 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 15 PY 2007 VL 357 IS 20 BP 2001 EP 2015 DI 10.1056/NEJMoa0706482 PG 15 WC Medicine, General & Internal SC General & Internal Medicine GA 230RV UT WOS:000250894500003 PM 17982182 ER PT J AU Babyatsky, MW Keroack, MD Blake, MA Rosenberg, ES Mino-Kenudson, M AF Babyatsky, Mark W. Keroack, Myles D. Blake, Michael A. Rosenberg, Eric S. Mino-Kenudson, Mari TI A 30-year-old man with inflammatory bowel disease and recent onset of fever and bloody diarrhea - Acute CMV infection in a patient with inflammatory bowel disease. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID PORTAL-VEIN THROMBOSIS; ULCERATIVE-COLITIS PATIENTS; CYTOMEGALOVIRUS-INFECTION; RELATIVE BRADYCARDIA; CROHNS-DISEASE; TYPHOID-FEVER; PREVALENCE; SALMONELLA; EXPRESSION; AMEBIASIS C1 Mt Sinai Med Ctr, Dept Med, New York, NY 10029 USA. Mt Sinai Sch Med, New York, NY USA. Massachusetts Gen Hosp, Dept Gastroenterol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Babyatsky, MW (reprint author), Mt Sinai Med Ctr, Dept Med, New York, NY 10029 USA. NR 38 TC 10 Z9 11 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 15 PY 2007 VL 357 IS 20 BP 2068 EP 2076 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 230RV UT WOS:000250894500011 PM 18003964 ER PT J AU Rusch, D Braun, HA Wulf, H Schuster, A Raines, DE AF Ruesch, Dirk Braun, Hans A. Wulf, Hinnerk Schuster, Anika Raines, Douglas E. TI Inhibition of human 5-HT3A and 5-HT3AB receptors by etomidate, propofol and pentobarbital SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE etomidate; propofol; pentobarbital; 5-HT3A receptor; 5-HT3AB receptor ID OUTSIDE-OUT PATCHES; GATED ION CHANNELS; BASIC PROPERTIES; SUBUNIT; CELLS; HIPPOCAMPUS; ACTIVATION; EXPRESSION AB The actions of intravenous anaesthetics on 5-HT3AB receptors have not been studied. Using oocyte electrophysiology, the effects of etomidate, propofol, and pentobarbital on human 5-HT3A and 5-HT3AB receptors were studied and compared. Inhibition of peak currents by all three compounds in both receptor subtypes was anaesthetic concentration-dependant and non-competitive. Because the half-maximal inhibitory concentrations for etomidate, propofol and pentobarbital in 5-HT3A and 5-HT3AB receptors were all above their respective anaesthetic concentrations, the results of our study suggest that neither 5-HT3 receptor subtype contributes to the anaesthetic actions of etomidate, propofol or pentobarbital. (c) 2007 Elsevier B.V. All rights reserved. C1 Univ Hosp Giessen Marburg GmbH, Dept Anaesthesia & Crit Care, D-35033 Marburg, Germany. Univ Marburg, Inst Physiol & Pathophysiol, Div Neuroendocrinol & Neurodynam, Marburg, Germany. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. RP Rusch, D (reprint author), Univ Hosp Giessen Marburg GmbH, Dept Anaesthesia & Crit Care, Marburg Campus,Baldingerstr, D-35033 Marburg, Germany. EM ruesch@staff.uni-marburg.de FU NIGMS NIH HHS [P01 GM058448, P01-GM58448, P01 GM058448-01] NR 18 TC 9 Z9 9 U1 0 U2 0 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 14 PY 2007 VL 573 IS 1-3 BP 60 EP 64 DI 10.1016/j.ejphar.2007.07.009 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 222ID UT WOS:000250288700008 PM 17669396 ER PT J AU Sinha, S Subramanian, S Proctor, TM Kaler, LJ Grafe, M Dahan, R Huan, J Vandenbark, AA Burrows, GG Offner, H AF Sinha, Sushmita Subramanian, Sandhya Proctor, Thomas M. Kaler, Laurie J. Grafe, Marjorie Dahan, Rony Huan, Jianya Vandenbark, Arthur A. Burrows, Gregory G. Offner, Halina TI A promising therapeutic approach for multiple sclerosis: recombinant T-cell receptor ligands modulate experimental autoimmune encephalomyelitis by reducing interleukin-17 production and inhibiting migration of encephalitogenic cells into the CNS SO JOURNAL OF NEUROSCIENCE LA English DT Article DE EAE; RTL; CNS; IL-17; chemokines/receptors; SH ID CENTRAL-NERVOUS-SYSTEM; TUMOR-NECROSIS-FACTOR; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; CXC CHEMOKINE RECEPTORS; MICE LACKING; FACTOR-ALPHA; SPINAL-CORD; EXPRESSION; INFLAMMATION; EAE AB Recombinant T-cell receptor ligands (RTLs) can prevent and reverse clinical and histological signs of experimental autoimmune encephalomyelitis (EAE) in an antigen-specific manner and are currently in clinical trials for treatment of subjects with multiple sclerosis (MS). To evaluate regulatory mechanisms, we designed and tested RTL551, containing the alpha 1 and beta 1 domains of the I-A(b) class II molecule covalently linked to the encephalitogenic MOG-35-55 peptide in C57BL/6 mice. Treatment of active or passive EAE with RTL551 after disease onset significantly reduced clinical signs and spinal cord lesions. Moreover, RTL551 treatment strongly and selectively reduced secretion of interleukin-17 and tumor necrosis factor alpha by transferred green fluorescent protein-positive (GFP+) MOG-35-55-reactive T-cells and almost completely abrogated existent GFP+ cellular infiltrates in affected spinal cord sections. Reduced inflammation in spinal cords of RTL551-treated mice was accompanied by a highly significant downregulation of chemokines and their receptors and inhibition of VCAM-1 (vascular cell adhesion molecule-1) and ICAM-1 (intercellular adhesion molecule-1) expression by endothelial cells. Thus, RTL therapy cannot only inhibit systemic production of encephalitogenic cytokines by the targeted myelin oligodendrocyte glycoprotein-reactive T-cells but also impedes downstream local recruitment and retention of inflammatory cells in the CNS. These findings indicate that targeted immunotherapy of antigen-specific T-cells can result in a reversal of CNS lesion formation and lend strong support to the application of the RTL approach for therapy in MS. C1 Portland VA Med Ctr, Neuroimmunol Res R&D 31, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Dept Pathol, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Dept Anesthesiol & Periopert Med, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Dept Mol Microbiol & Immunol, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Dept Biochem & Mol Biol, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Tykeson MS Res Lab, Portland, OR 97239 USA. RP Offner, H (reprint author), Portland VA Med Ctr, Neuroimmunol Res R&D 31, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM offnerva@ohsu.edu FU NIAID NIH HHS [AI43960]; NINDS NIH HHS [NS41965, NS46877, NS47661] NR 49 TC 33 Z9 34 U1 0 U2 0 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 14 PY 2007 VL 27 IS 46 BP 12531 EP 12539 DI 10.1523/JNEUROSCI.3599-07.2007 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 231NA UT WOS:000250952700012 PM 18003831 ER PT J AU Ikeda, S Kong, SW Lu, J Bisping, E Zhang, H Allen, PD Golub, TR Pieske, B Pu, WT AF Ikeda, Sadakatsu Kong, Sek Won Lu, Jun Bisping, Egbert Zhang, Hao Allen, Paul D. Golub, Todd R. Pieske, Burkert Pu, William T. TI Altered microRNA expression in human heart disease SO PHYSIOLOGICAL GENOMICS LA English DT Article DE heart failure; gene expression; expression profiling ID MUSCLE-SPECIFIC MICRORNA; IDENTIFICATION; CARDIOGENESIS; GENOMICS; FAILURE; GENES AB MicroRNAs are recently discovered regulators of gene expression and are becoming increasingly recognized as important regulators of heart function. Genome-wide profiling of microRNAs in human heart failure has not been reported previously. We measured expression of 428 microRNAs in 67 human left ventricular samples belonging to control (n = 10), ischemic cardiomyopathy (ICM, n = 19), dilated cardiomyopathy (DCM, n = 25), or aortic stenosis (AS, n = 13) diagnostic groups. miRNA expression between disease and control groups was compared by ANOVA with Dunnett's post hoc test. We controlled for multiple testing by estimating the false discovery rate. Out of 428 microRNAs measured, 87 were confidently detected; 43 were differentially expressed in at least one disease group. In supervised clustering, microRNA expression profiles correctly grouped samples by their clinical diagnosis, indicating that microRNA expression profiles are distinct between diagnostic groups. This was further supported by class prediction approaches, in which the class (control, ICM, DCM, AS) predicted by a microRNA-based classifier matched the clinical diagnosis 69% of the time (P < 0.001). These data show that expression of many microRNAs is altered in heart disease and that different types of heart disease are associated with distinct changes in microRNA expression. These data will guide further studies of the contribution of microRNAs to heart disease pathogenesis. C1 [Ikeda, Sadakatsu; Kong, Sek Won; Bisping, Egbert; Pu, William T.] Childrens Hosp, Harvard Med Sch, Dept Cardiol, Dept Genet, Boston, MA 02115 USA. [Lu, Jun; Zhang, Hao; Golub, Todd R.] Dana Farber Canc Inst, Harvard Med Sch, Dept Pediat Oncol, Boston, MA 02115 USA. [Lu, Jun; Zhang, Hao; Golub, Todd R.] MIT, Broad Inst Harvard, Cambridge, MA 02139 USA. [Bisping, Egbert; Pieske, Burkert] Univ Gottingen, Dept Cardiol & Pneumol, D-3400 Gottingen, Germany. [Allen, Paul D.] Brigham & Womens Hosp, Harvard Med Sch, Dept Anesthesia Perioperat & Pain Med, Boston, MA 02115 USA. [Golub, Todd R.] Childrens Hosp, Boston, MA 02115 USA. [Golub, Todd R.] Howard Hughes Med Inst, Chevy Chase, MD USA. RP Pu, WT (reprint author), Childrens Hosp, Harvard Med Sch, Dept Cardiol, Dept Genet, 320 Longwood Ave, Boston, MA 02115 USA. EM wpu@enders.tch.harvard.edu FU NHLBI NIH HHS [P01 HL-074734, HL-66582] NR 24 TC 323 Z9 360 U1 1 U2 29 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1094-8341 J9 PHYSIOL GENOMICS JI Physiol. Genomics PD NOV 14 PY 2007 VL 31 IS 3 BP 367 EP 373 DI 10.1152/physiolgenomics.00144.2007 PG 7 WC Cell Biology; Genetics & Heredity; Physiology SC Cell Biology; Genetics & Heredity; Physiology GA 243FM UT WOS:000251780600002 PM 17712037 ER PT J AU Stevenson, B Choy, HA Pinne, M Rotondi, ML Miller, MC DeMoll, E Kraiczy, P Cooley, AE Creamer, TP Suchard, MA Brissette, CA Verma, A Haake, DA AF Stevenson, Brian Choy, Henry A. Pinne, Marija Rotondi, Matthew L. Miller, M. Clarke DeMoll, Edward Kraiczy, Peter Cooley, Anne E. Creamer, Trevor P. Suchard, Marc A. Brissette, Catherine A. Verma, Ashutosh Haake, David A. TI Leptospira interrogans Endostatin-Like Outer Membrane Proteins Bind Host Fibronectin, Laminin and Regulators of Complement SO PLOS ONE LA English DT Article AB The pathogenic spirochete Leptospira interrogans disseminates throughout its hosts via the bloodstream, then invades and colonizes a variety of host tissues. Infectious leptospires are resistant to killing by their hosts' alternative pathway of complement-mediated killing, and interact with various host extracellular matrix (ECM) components. The LenA outer surface protein (formerly called LfhA and Lsa24) was previously shown to bind the host ECM component laminin and the complement regulators factor H and factor H-related protein-1. We now demonstrate that infectious L. interrogans contain five additional paralogs of lenA, which we designated lenB, lenC, lenD, lenE and lenF. All six genes encode domains predicted to bear structural and functional similarities with mammalian endostatins. Sequence analyses of genes from seven infectious L. interrogans serovars indicated development of sequence diversity through recombination and intragenic duplication. LenB was found to bind human factor H, and all of the newly-described Len proteins bound laminin. In addition, LenB, LenC, LenD, LenE and LenF all exhibited affinities for fibronectin, a distinct host extracellular matrix protein. These characteristics suggest that Len proteins together facilitate invasion and colonization of host tissues, and protect against host immune responses during mammalian infection. C1 [Stevenson, Brian; Cooley, Anne E.; Brissette, Catherine A.; Verma, Ashutosh] Univ Kentucky, Coll Med, Dept Microbiol Mol Genet & Immunol, Lexington, KY 40506 USA. [Choy, Henry A.; Pinne, Marija; Haake, David A.] Vet Affairs Greater Los Angeles Hlth Care Syst, Div Infect Dis, Los Angeles, CA USA. [Choy, Henry A.; Pinne, Marija; Haake, David A.] Univ Calif Los Angeles, Dept Med, Sch Med, Los Angeles, CA 90024 USA. [Rotondi, Matthew L.; Miller, M. Clarke; DeMoll, Edward] Univ Kentucky, Dept Chem, Lexington, KY 40506 USA. [Kraiczy, Peter] Univ Hosp Frankfurt, Inst Med Microbiol & Infect Control, Frankfurt, Germany. [Creamer, Trevor P.] Univ Kentucky, Coll Med, Dept Mol & Cellular Biochem, Lexington, KY USA. [Suchard, Marc A.] Univ Calif Los Angeles, Sch Med, Dept Biomath, Los Angeles, CA 90024 USA. [Verma, Ashutosh] Univ Kentucky, Dept Vet Sci, Lexington, KY 40546 USA. RP Stevenson, B (reprint author), Univ Kentucky, Coll Med, Dept Microbiol Mol Genet & Immunol, Lexington, KY 40506 USA. EM brian.stevenson@uky.edu RI Miller, Clarke/C-9483-2011; OI Miller, Montie/0000-0002-9877-6581 FU VA Medical Research funds; National 10 Institute of Allergy and Infectious Diseases [AI-34431]; Paul Mellon Fellowship FX This work was funded in part by VA Medical Research funds and National 10 Institute of Allergy and Infectious Diseases grant AI-34431 to D. Haake. M. Suchard is an Alfred P. Sloan Research Fellow. A. Verma was supported by a Paul Mellon Fellowship in Equine Studies. NR 71 TC 115 Z9 117 U1 2 U2 11 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD NOV 14 PY 2007 VL 2 IS 11 AR e1188 DI 10.1371/journal.pone.0001188 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V10JA UT WOS:000207459100026 PM 18000555 ER PT J AU Yamamoto-Furusho, JK Podolsky, DK AF Yamamoto-Furusho, Jesus K. Podolsky, Daniel K. TI Innate immunity in inflammatory bowel disease SO WORLD JOURNAL OF GASTROENTEROLOGY LA English DT Article DE innate; immunity; toll-like receptors; inflammatory bowel disease ID INTESTINAL EPITHELIAL-CELLS; COLONY-STIMULATING FACTOR; ACTIVE CROHNS-DISEASE; NOD2; SUSCEPTIBILITY; PEPTIDOGLYCAN; EXPRESSION; DIPEPTIDE; MUTATIONS; GENE AB The human intestinal tract is home to an enormous bacterial flora. The host defense against microorganisms can be divided into innate and adaptive immunity. The former is the most immediate line of response to immunologic challenges presented by bacteria, viruses, and fungi. The mucosal immune system has evolved to balance the need to respond to pathogens while co-existing with commensal bacteria and food antigens. In inflammatory bowel disease (IBD), this hyporesponsiveness or tolerance breaks down and inflammation supervenes driven by the intestinal microbial flora. Bacteria contain compounds and are recognized by a variety of receptors, including Toll-like receptors (TLRs) and NODs (a family of intracellular bacterial sensors) and are potent stimuli of innate immune responses. Several mutations in these receptors have been associated with development of IBD. (c) 2007 WJG. All rights reserved. C1 Massachusetts Gen Hosp, Gastroenterol Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Harvard Med Sch, Gastroenterol Unit, Boston, MA 02114 USA. RP Yamamoto-Furusho, JK (reprint author), Massachusetts Gen Hosp, Gastroenterol Unit, 55 Fruit St, Boston, MA 02114 USA. EM kazuofurusho@hotmail.com NR 37 TC 41 Z9 43 U1 0 U2 4 PU W J G PRESS PI BEIJING PA APT 1066, YISHOU GARDEN, NO 58, NORTH LANGXINZHUANG RD, PO BOX 2345, BEIJING 100023, PEOPLES R CHINA SN 1007-9327 J9 WORLD J GASTROENTERO JI World J. Gastroenterol. PD NOV 14 PY 2007 VL 13 IS 42 BP 5577 EP 5580 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 221MQ UT WOS:000250232400005 PM 17948931 ER PT J AU Kawada, M Arihiro, A Mizoguchi, E AF Kawada, Mayumi Arihiro, Atsuko Mizoguchi, Emiko TI Insights from advances in research of chemically induced experimental models of human inflammatory bowel disease SO WORLD JOURNAL OF GASTROENTEROLOGY LA English DT Review DE inflammatory bowel disease; experimental colitis; dextran sodium sulfate; trinitrobenzene sulfonic acid; oxazolone; pathogenesis ID DEXTRAN SULFATE SODIUM; ACID-INDUCED COLITIS; TNBS-INDUCED COLITIS; NF-KAPPA-B; CHRONIC INTESTINAL INFLAMMATION; EXPERIMENTAL MURINE COLITIS; TUMOR-NECROSIS-FACTOR; HAPTEN-INDUCED COLITIS; DELTA-T-CELLS; ACTIVATED-RECEPTOR-GAMMA AB Inflammatory bowel disease (IBD), the most important being Crohn's disease and ulcerative colitis, results from chronic dysregulation of the mucosal immune system in the gastrointestinal tract. Although the pathogenesis of IBD remains unclear, it is widely accepted that genetic, environmental, and immunological factors are involved. Recent studies suggest that intestinal epithelial defenses are important to prevent inflammation by protecting against microbial pathogens and oxidative stresses. To investigate the etiology of IBD, animal models of experimental colitis have been developed and are frequently used to evaluate new anti-inflammatory treatments for IBD. Several models of experimental colitis that demonstrate various pathophysiological aspects of the human disease have been described. In this manuscript, we review the characteristic features of IBD through a discussion of the various chemically induced experimental models of colitis (e.g. dextran sodium sulfate-, 2,4,6-trinitrobenzene sulfonic acid-, oxazolone-, acetic acid-, and indomethacin-induced models). We also summarize some regulatory and pathogenic factors demonstrated by these models that can, hopefully, be exploited to develop future therapeutic strategies against IBD. (c) 2007 WJG. All rights reserved. C1 Massachusetts Gen Hosp, Harvard Med Sch, Gastrointestinal Unit, GRJ 702, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Study Inflammatory Bowel Dis, Harvard Med Sch, Boston, MA 02114 USA. RP Mizoguchi, E (reprint author), Massachusetts Gen Hosp, Harvard Med Sch, Gastrointestinal Unit, GRJ 702, 55 Fruit St, Boston, MA 02114 USA. EM emizoguchi@partners.org FU NIDDK NIH HHS [DK74454, DK43351, DK64289, K08 DK064289, P30 DK043351, R03 DK074454] NR 186 TC 90 Z9 94 U1 2 U2 14 PU W J G PRESS PI BEIJING PA APT 1066, YISHOU GARDEN, NO 58, NORTH LANGXINZHUANG RD, PO BOX 2345, BEIJING 100023, PEOPLES R CHINA SN 1007-9327 J9 WORLD J GASTROENTERO JI World J. Gastroenterol. PD NOV 14 PY 2007 VL 13 IS 42 BP 5581 EP 5593 PG 13 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 221MQ UT WOS:000250232400006 PM 17948932 ER PT J AU Nallamothu, BK Wang, YF Cram, P Birkmeyer, JD Ross, JS Normand, SLT Krumholz, HM AF Nallamothu, Brahmajee K. Wang, Yongfei Cram, Peter Birkmeyer, John D. Ross, Joseph S. Normand, Sharon-Lise T. Krumholz, Harlan M. TI Acute myocardial infarction and congestive heart failure outcomes at specialty cardiac hospitals SO CIRCULATION LA English DT Article DE cardiac care facilities; myocardial infarction; heart failure, congestive; outcomes research ID REVASCULARIZATION; QUALITY; CARE AB Background-Outcomes of patients with acute myocardial infarction (AMI) and congestive heart failure (CHF) at specialty cardiac hospitals are uncertain. Methods and Results-From 2003 Medicare data, we used hierarchical regression to calculate 30-day standardized mortality ratios and risk-standardized mortality rates for AMI and CHF at 16 cardiac and 121 peer general hospitals in 15 healthcare markets. We then compared cardiac and general hospitals by determining (1) the proportion of facilities with statistically higher, no different, or lower than expected mortality based on 95% interval estimates of standardized mortality ratios and (2) differences in risk-standardized mortality rates between the types of facilities after stratification within healthcare markets. We identified 1912 patients with AMI and 1275 patients with CHF at cardiac hospitals and 13 158 patients with AMI and 18 295 patients with CHF at general hospitals. Patients at cardiac hospitals were younger, were more likely to be male, and had a much lower prevalence of noncardiovascular diseases. After adjustment for patient differences, standardized mortality ratios were significantly better than expected for 4 (25%) and 5 (31%) cardiac hospitals for AMI and CHF, respectively, compared with 5 (4%) and 6 (5%) general hospitals. Risk-standardized mortality rates were modestly lower at cardiac hospitals (15.0% versus 16.2% for AMI, P<0.001, and 10.7% versus 11.3% for CHF, P<0.01). Conclusions-Patients with AMI and CHF at cardiac hospitals differ considerably from those at peer general hospitals. Although outcomes were modestly better at cardiac hospitals, substantial variation was noted across individual facilities. C1 Univ Michigan, Sch Med, Hlth Serv Res & Dev Ctr Excellence, Ann Arbor VA Med Ctr,Dept Internal Med, Ann Arbor, MI 48109 USA. Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, Sect Hlth Policy & Adm, New Haven, CT USA. Univ Iowa, Dept Med, Iowa City, IA USA. Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA. Mt Sinai Sch Med, Dept Geriatr & Adult Dev, New York, NY USA. James J Peters VA Med Ctr, HSR&D Targeted Res Enhancement Program & Geriatr, Bronx, NY USA. Harvard Med Sch, Dept Biostat, Boston, MA USA. Harvard Sch Publ Hlth, Dept Biostat, Boston, MA USA. Yale Univ, Yale New Haven Hosp, Sch Med, Ctr Outcomes Res & Evaluat,Robert Wood Johnson C, New Haven, CT USA. RP Nallamothu, BK (reprint author), 1500 E Med Ctr Dr, Ann Arbor, MI 48109 USA. EM bnallamo@umich.edu RI Cram, Peter/K-4472-2014 OI Cram, Peter/0000-0002-1910-346X FU AHRQ HHS [1R01HS015571-01A1] NR 13 TC 18 Z9 18 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 13 PY 2007 VL 116 IS 20 BP 2280 EP 2287 DI 10.1161/CIRCULATIONAHA.107.709220 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 230IT UT WOS:000250870900008 PM 17967975 ER PT J AU Das, F Mahimainathan, L Ghosh-Choudhury, N Venkatesan, B Kasinath, BS Abboud, HE Choudhury, GG AF Das, Falguni Mahimainathan, Lenin Ghosh-Choudhury, Nandini Venkatesan, Balachandar Kasinath, Balakuntalam S. Abboud, Hanna E. Choudhury, Goutam Ghosh TI TGF beta intercepts nuclear glycogen synthase kinase 3 beta to inhibit PDGF-induced DNA synthesis in mesangial cells SO FEBS LETTERS LA English DT Article DE Akt kinase; GSK3 beta; cyclin D1; CDK2; mitogenesis; glomerulonephritis ID GROWTH-FACTOR; KINASE 3-BETA; CYCLIN D1; AKT; PHOSPHORYLATION; PROLIFERATION; ACTIVATION; MECHANISM; LOCALIZATION; DOWNSTREAM AB Here, we demonstrate a mechanism of TGF beta-mediated inhibition of PDGF-induced DNA synthesis in mesangial cells. TGFb significantly inhibited nuclear Akt phosphorylation without any effect on PDGF-stimulated phosphorylation of PDGFR at PI 3 kinase binding site (Tyr-751). Remarkably, TGFb inhibited cyclin D1 and cyclin E expression with concomitant decrease in CDK2 activity induced by PDGF. More importantly, we demonstrate that TGFb significantly abolished Akt-mediated serine-9 phosphorylation of glycogen synthase kinase 3 beta (GSK3 beta), thus prevented its inactivation. Expression of inactive GSK3 beta K85R mutant increased cyclin D1 expression and DNA synthesis similar to PDGF. These results provide the first evidence that TGFb intercepts Akt kinase activity in the nucleus to block inactivation of GSK3b, leading to attenuation of PDGF-induced CDK2 activity and DNA synthesis. (C) 2007 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved. C1 [Das, Falguni; Mahimainathan, Lenin; Venkatesan, Balachandar; Kasinath, Balakuntalam S.; Abboud, Hanna E.; Choudhury, Goutam Ghosh] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Ghosh-Choudhury, Nandini] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78284 USA. [Ghosh-Choudhury, Nandini; Kasinath, Balakuntalam S.; Abboud, Hanna E.; Choudhury, Goutam Ghosh] S Texas Vet Hlth Care Syst, San Antonio, TX USA. [Choudhury, Goutam Ghosh] Educ & Clin Ctr, San Antonio, TX USA. RP Choudhury, GG (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Med, Mail Code 7882,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM choudhuryg@uthscsa.edu FU NIAMS NIH HHS [R01 AR52425]; NIDDK NIH HHS [R01 DK33665, R01 DK077295, R01 DK50190] NR 34 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD NOV 13 PY 2007 VL 581 IS 27 BP 5259 EP 5267 DI 10.1016/j.febslet.2007.10.014 PG 9 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 267CU UT WOS:000253487700015 PM 17961557 ER PT J AU Williamson, PTF Verhoeven, A Miller, KW Meier, BH Watts, A AF Williamson, P. T. F. Verhoeven, A. Miller, K. W. Meier, B. H. Watts, A. TI The conformation of acetylcholine at its target site in the membrane-embedded nicotinic acetylcholine receptor SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE magic-angle spinning; membrane proteins; receptor pharmacology; solid-state NMR ID SOLID-STATE NMR; LIGAND-BINDING DOMAIN; AGONIST-BINDING; ROTATIONAL-RESONANCE; DRUG DISCOVERY; DISTANCE MEASUREMENTS; AMINO-ACIDS; IDENTIFICATION; SIMULATIONS; PROTEINS AB The conformation of the neurotransmitter acetylcholine bound to the fully functional nicotinic acetylcholine receptor embedded in its native membrane environment has been characterized by using frequency-selective recoupling solid-state NMR. Six dipolar couplings among five resolved C-13-labeled atoms of acetylcholine were measured. Bound acetylcholine adopts a bent conformation characterized with a quaternary ammonium-to-carbonyl distance of 5.1 angstrom. In this conformation, and with its orientation constrained to that previously determined by us, the acetylcholine could be docked satisfactorily in the agonist pocket of the agonist-bound, but not the agonist-free, crystal structure of a soluble acetylcholine-binding protein from Lymnaea stagnali. The quaternary ammonium group of the acetylcholine was determined to be within 3.9 A of five aromatic residues and its acetyl group close to residues C187/188 of the principle and residue L112 of the complementary subunit. The observed >C=O chemical shift is consistent with H bonding to the nicotinic acetylcholine receptor residues gamma Y116 and delta T119 that are homologous to L112 in the soluble acetylcholine-binding protein. C1 ETH, CH-8093 Zurich, Switzerland. Univ Oxford, Dept Biochem, Biomembrane Struct Unit, Oxford 1 3QU, England. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Anaesthesia & Crit Care, Boston, MA 02114 USA. Univ Southampton, Sch Biol Sci, Southampton SO16 7PX, Hants, England. CNRS, F-75700 Paris, France. RP Williamson, PTF (reprint author), ETH, Wolfgang Pauli Str 10, CH-8093 Zurich, Switzerland. EM P.T.Williamson@soton.ac.uk RI Williamson, Philip/A-3362-2008; Meier, Beat/K-4066-2016 OI Williamson, Philip/0000-0002-0231-8640; Meier, Beat/0000-0002-9107-4464 FU NIGMS NIH HHS [GM 58448, P01 GM058448]; Wellcome Trust NR 42 TC 37 Z9 37 U1 1 U2 22 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 13 PY 2007 VL 104 IS 46 BP 18031 EP 18036 DI 10.1073/pnas.0704785104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 233FY UT WOS:000251077000026 PM 17989232 ER PT J AU Feuerer, M Jiang, W Holler, PD Satpathy, A Campbell, C Bogue, M Mathis, D Benoist, C AF Feuerer, Markus Jiang, Wenyu Holler, Phillip D. Satpathy, Ansuman Campbell, Christopher Bogue, Molly Mathis, Diane Benoist, Christophe TI Enhanced thymic selection of FoxP3(+) regulatory T cells in the NOD mouse model of autoimmune diabetes SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE genetic; lineage commitment; thymus ID TRANSCRIPTION FACTOR FOXP3; LINKED LYMPHOPROLIFERATIVE-DISEASE; CLONAL DELETION; CENTRAL TOLERANCE; GENETIC-CONTROL; REG CELLS; MICE; INDUCTION; ANTIGEN; INTERLEUKIN-2 AB FoxP3(+)CD4(+) regulatory T cells (Tregs) play a key role in the maintenance of peripheral self-tolerance, and it has been suggested that diabetes-susceptible nonobese diabetic (NOD) mice are defective in the generation and numbers of Tregs. We found thymic selection of Tregs to be under genetic control. Fetal thymic organ cultures on the NOD background required 3- to 10-fold more antigen than corresponding cultures on the B6 background for optimal induction of Tregs, but once the threshold for induction was reached the NOD background yielded close to 10-fold more Tregs. This increased selection of Tregs was also found in non-transgenic NOD mice in fetal through adult stages. This trait did not map to the MHC, idd3, or the chromosome 3 (Chr3) regions that control clonal deletion, but mainly to two regions on Chr1 and Chr11. Thus, NOD mice do not have a global defect in the generation or maintenance of Tregs; if anything, they show the opposite. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp,Dept Med, Joslin Diabet Ctr,Sect Immunol & Immunogenet, Boston, MA 02215 USA. Jackson Lab, Bar Harbor, ME 04609 USA. RP Mathis, D (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp,Dept Med, Joslin Diabet Ctr,Sect Immunol & Immunogenet, Boston, MA 02215 USA. EM cbdm@joslin.harvard.edu FU NIDDK NIH HHS [1R01DK60027, R01 DK060027] NR 45 TC 51 Z9 51 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 13 PY 2007 VL 104 IS 46 BP 18181 EP 18186 DI 10.1073/pnas.0708899104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 233FY UT WOS:000251077000052 PM 17991775 ER PT J AU Gray, DHD Gavanescu, I Benoist, C Mathis, D AF Gray, Daniel H. D. Gavanescu, Irina Benoist, Christophe Mathis, Diane TI Danger-free autoimmune disease in Aire-deficient mice SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE autoimmunity; environment; immunological tolerance ID HUMORAL IMMUNE-RESPONSE; GERM-FREE; T-CELLS; INFLAMMATORY DISEASE; NEGATIVE SELECTION; TRANSGENIC MICE; RECEPTOR; TOLERANCE; ANTIGEN; PROTEIN AB The danger theory of immune tolerance asserts that environmental factors hold primacy over lymphocyte autoreactivity in initiating autoimmune disease. We sought to test this contention using the Aire-deficient mouse model of the human disease, autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy, a multiorgan autoimmune disorder rooted in a lesion in thymic tolerance. Compound screens stimulating a broad range of innate immune system pathways failed to show any modulation of disease characteristics in Aire(-/-) mice on either the C57BL/6 or NOD genetic backgrounds. Furthermore, deficiency in the Toll-like receptor adaptor Myd88 increased the lifespan of NOD.aire(-/-) mice but did not prevent the initiation of autoimmunity. Finally, germ-free NOD. aire(-/-) mice exhibited autoimmunity in all organs normally targeted in this model, indicating that microbial conditioning is not required for activation of autoreactive T cells relevant to this disease. Together, these data suggest that the stochastic genesis of dangerous T cell clones can initiate autoimmune disease without the need for environmental stimulation, underlining the importance of Aire-dependent thymic deletion. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp,Dept Med, Joslin Diabet Ctr,Sect Immunol & Immunogenet, Boston, MA 02215 USA. RP Benoist, C (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp,Dept Med, Joslin Diabet Ctr,Sect Immunol & Immunogenet, 1 Joslin Pl, Boston, MA 02215 USA. EM cbdm@joslin.harvard.edu; dm@joslin.harvard.edu RI Gray, Daniel/A-3293-2013 OI Gray, Daniel/0000-0002-8457-8242 FU NCI NIH HHS [T32 CA009382, T32 CA09382-22]; NIAID NIH HHS [F32 AI062010, F32 AI62010-01]; NIDDK NIH HHS [P30 DK036836, P30 DK36836, R01 DK060027, R01 DK60027] NR 32 TC 40 Z9 40 U1 0 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 13 PY 2007 VL 104 IS 46 BP 18193 EP 18198 DI 10.1073/pnas.0709160104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 233FY UT WOS:000251077000054 PM 17991771 ER PT J AU Giedraitis, V Sundelof, J Irizarry, MC Garevik, N Hyman, BT Wahlund, LO Ingelsson, M Lannfelt, L AF Giedraitis, Vilmantas Sundelof, Johan Irizarry, Michael C. Garevik, Nina Hyman, Bradley T. Wahlund, Lars-Olof Ingelsson, Martin Lannfelt, Lars TI The normal equilibrium between CSF and plasma amyloid beta levels is disrupted in Alzheimer's disease SO NEUROSCIENCE LETTERS LA English DT Article DE Alzheimer's disease; mild cognitive impairment (MCI); cerebrospinal fluid; case control studies; amyloid beta; APOE ID MILD-COGNITIVE-IMPAIRMENT; GAMMA-SECRETASE INHIBITOR; CEREBROSPINAL-FLUID; MOUSE MODEL; PROTEIN; BRAIN; A-BETA-42; DIAGNOSIS; RATIO; AGE AB Amyloid-beta (A beta) with 40 (A beta 40) and 42 (A beta 42) amino acids, the main components of amyloid plaques in the Alzheimer's disease (AD) brain, can be measured in human cerebrospinal fluid (CSF) and plasma. Whereas CSF A beta 42 is decreased in AD, some studies have reported changed plasma A beta levels in AD and in subjects with mild cognitive impairment (MCI). To this date it is unclear if and how CSF and plasma levels of A beta correlate with each other in healthy individuals, albeit earlier studies on AD patients found no correlation between CSF and plasma A beta. We have measured A beta 40 and A beta 42 in paired CSF and plasma samples from patients with AD (n=39), MCI (n=29) and healthy control subjects (n= 18). We observed a clear correlation between CSF and plasma levels for both A beta 40 and A beta 42 in healthy individuals, whereas no such correlation could be seen for AD or MCI cases. Similarly to other studies we also found low levels of A beta 42 in AD CSF, whereas there were no significant differences in plasma A beta levels between the diagnostic groups. Our findings suggest that the normal equilibrium between CSF and plasma A beta may be disrupted with the initiation of amyloid deposition in the brain. (c) 2007 Elsevier Ireland Ltd. All rights reserved. C1 Uppsala Univ, Dept Publ Hlth Geriatr, Uppsala, Sweden. Massachusetts Gen Hosp, Boston, MA 02114 USA. Karolinska Univ Hosp, Stockholm, Sweden. RP Giedraitis, V (reprint author), Mol Geriatr Rudbeck Lab, SE-75185 Uppsala, Sweden. EM Vilmantas.Giedraitis@pubcare.uu.se OI wahlund, lars-olof/0000-0002-9905-8426 FU NIA NIH HHS [AG05134]; NINDS NIH HHS [1 T32 NS048005-01, T32 NS048005] NR 27 TC 54 Z9 57 U1 1 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD NOV 12 PY 2007 VL 427 IS 3 BP 127 EP 131 DI 10.1016/j.neulet.2007.09.023 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 237ON UT WOS:000251384800002 PM 17936506 ER PT J AU Caetano, SC Fonseca, M Hatch, JP Olvera, RL Nicoletti, M Hunter, K Lafer, B Pliszka, SR Soares, JC AF Caetano, Sheila C. Fonseca, Manoela Hatch, John P. Olvera, Rene L. Nicoletti, Mark Hunter, Kristina Lafer, Beny Pliszka, Steven R. Soares, Jair C. TI Medial temporal lobe abnormalities in pediatric unipolar depression SO NEUROSCIENCE LETTERS LA English DT Article; Proceedings Paper CT 60th Annual Convention of the Society-of-Biological-Psychiatry CY MAY 19-21, 2005 CL Atlanta, GA SP Soc Biol Psychiat DE major depressive disorder; children; adolescents; hippocampus; amygdala; MRI ID RECURRENT MAJOR DEPRESSION; HIPPOCAMPAL VOLUME LOSS; DISORDER; AMYGDALA; ADOLESCENTS; DURATION; REDUCTION; BRAIN; PREDICTORS; SEVERITY AB In vivo anatomical magnetic resonance imaging (MRI) studies in adults with major depressive disorder (MDD) have implicated neurocircuitries involved in mood regulation in the pathophysiology of mood disorders. Specifically, abnormalities in the medial temporal lobe structures have been reported. This study examined a sample of children and adolescents with major depressive disorder to investigate anatomical abnormalities in these key medial temporal brain regions. Nineteen children and adolescents with DSM-IV major depression (mean age +/- S.D. = 13.0 +/- 2.4 years; 10 unmedicated) and 24 healthy comparison subjects (mean age +/- S.D. = 13.9 +/- 2.9 years) were studied using a 1.5 T Philips MRI scanner. We measured hippocampus and amygdala gray matter volumes. MRI structural volumes were compared using analysis of covariance with age and total brain volumes as covariates. Pediatric depressed patients had significantly smaller left hippocampal gray matter volumes compared to healthy controls (1.89 +/- 0.16 cm(3) versus 1.99 +/- 0.18 cm(3), respectively; F= 5.0, d.f. = 1/39, p = 0.03; effect size: eta(2)(p) = 0.11). Unmedicated depressed patients showed a trend towards smaller left hippocampal volumes compared to medicated patients and healthy subjects (F=2.8, d.f. = 2/38, p = 0.07; effect size: eta(2)(p) = 0.13). There were no statistically significant differences in mean volumes for left or right amygdala. Smaller left hippocampal volumes in children and adolescents with MDD are in agreement with findings from adult studies and suggest that such abnormalities are present early in the course of the illness. Amygdala volumes are not abnormal in this age group. Smaller hippocampal volumes may be related to an abnormal developmental process or HPA axis dysfunction. (c) 2007 Published by Elsevier Ireland Ltd. C1 Univ N Carolina, Sch Med, Dept Psychiat, CERT BD, Chapel Hill, NC 27599 USA. Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, Div Mood & Anxiety Disorders, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Psychiat Serv, Audie L Murphy Div, San Antonio, TX USA. Univ Sao Paulo, Sch Med, Dept Psychiat, Sao Paulo, Brazil. Univ Fed Rio Grande do Sul, Sch Med, Psychiat Res Unit, Porto Alegre, RS, Brazil. Univ Texas Hlth Sci Ctr San Antonio, Dept Orthodont, San Antonio, TX 78229 USA. Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, Div Child & Adolescent Psychiat, San Antonio, TX 78229 USA. RP Soares, JC (reprint author), Univ N Carolina, Sch Med, Dept Psychiat, CERT BD, 10616 Neurosci Hosp,CB 7160, Chapel Hill, NC 27599 USA. EM jsoares@med.unc.edu RI Lafer, Beny/C-1055-2012; Caetano, Sheila/H-5010-2012; Lafer, Beny/F-9390-2015 OI Lafer, Beny/0000-0002-6132-9999; Caetano, Sheila/0000-0001-8403-7078; Lafer, Beny/0000-0002-6132-9999 FU NCRR NIH HHS [RR020571, M01 RR01346]; NIMH NIH HHS [MH69774, K23 MH068280, MH068662] NR 42 TC 35 Z9 49 U1 4 U2 13 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD NOV 12 PY 2007 VL 427 IS 3 BP 142 EP 147 DI 10.1016/j.neulet.2007.06.014 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 237ON UT WOS:000251384800005 PM 17949901 ER PT J AU Moinpour, CM Denicoff, AM Bruner, DW Kornblith, AB Land, SR O'Mara, A Trimble, E AF Moinpour, Carol M. Denicoff, Andrea M. Bruner, Deborah Watkins Kornblith, Alice B. Land, Stephanie R. O'Mara, Ann Trimble, Edward TI Funding patient-reported outcomes in cancer clinical trials SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID FUNCTIONAL LIVING INDEX; QUALITY; LIFE AB We surveyed four cooperative groups to identify current funding sources for the collection and analysis effort associated with the inclusion of patient-reported outcome (PRO) data in cancer clinical trials. Survey questions included what proportion of staff effort was funded through the Cancer Therapy Evaluation Program (CTEP) and the Community Clinical Oncology Program (CCOP) grants. In addition, the groups were asked to what extent outside funding was solicited to cover an underfunded PRO effort (eg, the pharmaceutical industry, foundations, or National Institutes of Health grants). All four groups noted the challenge of making limited resources cover a number of trial responsibilities. PRO effort is usually bundled with effort required for all clinical trial data. There is variation in the use of the CTEP and CCOP grants to fund PRO research. The groups differed with respect to both the types and amount of outside funding used. This survey focused on funding sources for the conduct of PRO research in cooperative group trials; it did not assess the specific cost components associated with collecting and analyzing these data. In general, the costs for conducting PRO research have been bundled with other study costs because in most cases, the PRO has been considered an integral component of the trial. However, these data also suggest that PRO research has required the use of outside funding sources in the four surveyed cooperative groups and that PRO economic issues require attention if we are to continue the inclusion of these outcomes in cancer clinical trials. C1 Fred Hutchinson Canc Res Ctr, Ctr Stat, SW Oncol Grp, Seattle, WA 98104 USA. NCI, Clin Invest Branch, Canc Therapy Evaluat Program, NIH, Bethesda, MD 20892 USA. NCI, Community Clin Oncol Program, NIH, Bethesda, MD 20892 USA. Univ Penn, Radiat Therapy Oncol Grp, Philadelphia, PA 19104 USA. Univ Pittsburgh, Natl Surg Adjuvant Breast & Bowel Program, Ctr Biostat, Pittsburgh, PA USA. Univ Pittsburgh, Dept Biostat, Pittsburgh, PA 15261 USA. Dana Farber Canc Ctr, Canc & Leukemia Grp B, Boston, MA USA. RP Moinpour, CM (reprint author), Fred Hutchinson Canc Res Ctr, Ctr Stat, SW Oncol Grp, MS-C102,1100 Fairview Ave N,Box 19024, Seattle, WA 98104 USA. EM cmoinpou@fhcrc.org FU NCI NIH HHS [CA31946, CA38926, CA069974, CA37422, CA37429, CA21661, CA32115] NR 31 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV 10 PY 2007 VL 25 IS 32 BP 5100 EP 5105 DI 10.1200/JCO.2007.11.5329 PG 6 WC Oncology SC Oncology GA 233EW UT WOS:000251074200010 PM 17991928 ER PT J AU Pauli-Magnus, D Hoch, G Strenzke, N Anderson, S Jentsch, TJ Moser, T AF Pauli-Magnus, D. Hoch, G. Strenzke, N. Anderson, S. Jentsch, T. J. Moser, T. TI Detection and differentiation of sensorineural hearing loss in mice using auditory steady-state responses and transient auditory brainstem responses SO NEUROSCIENCE LA English DT Article DE cochlea; hair cell; synapse; amplification; threshold; mouse model ID AMPLITUDE-MODULATED TONES; OUTER HAIR-CELLS; DOMINANT DEAFNESS; CHANNELS; AUDIOMETRY; KCNQ4; POTENTIALS; PARAMETERS; PRESTIN; PATHWAY AB Sensorineural hearing loss (SNHL) comprises hearing disorders with diverse pathologies of the inner ear and the auditory nerve. To date, an unambiguous phenotypical characterization of the specific pathologies in an affected individual remains impossible. Here, we evaluated the use of scalp-recorded auditory steady-state responses (ASSR) and transient auditory brainstem responses (ABR) for differentiating the disease mechanisms underlying sensorineural hearing loss in well-characterized mouse models. We first characterized the ASSR evoked by sinusoidally amplitude-modulated tones in wild-type mice. ASSR were robustly elicited within three ranges of modulation frequencies below 200 Hz, from 200 to 600 Hz and beyond 600 Hz in most recordings. Using phase information we estimated the apparent ASSR latency to be about 3 ms, suggesting generation in the auditory brainstem. Auditory thresholds obtained by automated and visual analysis of ASSR recordings were comparable to those found with tone-burst evoked ABR in the same mice. We then recorded ASSR and ABR from mouse mutants bearing defects of either outer hair cell amplification (KC NQ4- knockout) or inner hair cell synaptic transmission (Bassoon-mutant). Both mutants showed an increase of ASSR and ABR thresholds of approximately 40 dB versus wild-type when investigated at 8 weeks of age. Mice with defective amplification displayed a steep rise of ASSR and ABR amplitudes with increasing sound intensity, presumably reflecting a strong recruitment of synchronously activated neural elements beyond threshold. In contrast, the amplitudes of ASSR and ABR responses of mice with impaired synaptic transmission grew very little with sound intensity. In summary, ASSR allow for a rapid, objective and frequency-specific hearing assessment and together with ABR and otoacoustic emissions can contribute to the differential diagnosis of SNHL. (C) 2007 IBRO. Published by Elsevier Ltd. All rights reserved. C1 Univ Gottingen, Sch Med, Dept Otolaryngol, InnerEarLab, D-37099 Gottingen, Germany. Univ Gottingen, Ctr Mol Physiol Brain, Dept Otolaryngol, InnerEarLab, Gottingen, Germany. Harvard Univ, Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02115 USA. Max Delbruck Centrum Mol Med, Leibniz Inst Mol Pharmakol, Berlin, Germany. Univ Gottingen, Bernstein Ctr Comp Neurosci, D-3400 Gottingen, Germany. RP Moser, T (reprint author), Univ Gottingen, Sch Med, Dept Otolaryngol, InnerEarLab, D-37099 Gottingen, Germany. EM tmoser@gwdg.de RI Horstmann, Britta/C-2154-2008; Moser, Tobias/L-5068-2014; OI Moser, Tobias/0000-0001-7145-0533; Jentsch, Thomas/0000-0002-3509-2553 NR 38 TC 14 Z9 15 U1 0 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD NOV 9 PY 2007 VL 149 IS 3 BP 673 EP 684 DI 10.1016/j.neuroscience.2007.08.010 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 232MD UT WOS:000251022900020 PM 17869440 ER PT J AU Jagsi, R Tarbell, NJ Weinstein, DF AF Jagsi, Reshma Tarbell, Nancy J. Weinstein, Debra F. TI Becoming a doctor, starting a family - Leave of absence from graduate medical education SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 Univ Michigan, Sch Med, Ann Arbor, MI 48109 USA. Harvard Univ, Sch Med, Ctr Fac Dev, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Off Womens Careers, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Partners HealthCare Syst, Boston, MA USA. RP Jagsi, R (reprint author), Univ Michigan, Sch Med, Ann Arbor, MI 48109 USA. OI Jagsi, Reshma/0000-0001-6562-1228 NR 5 TC 13 Z9 13 U1 0 U2 3 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 8 PY 2007 VL 357 IS 19 BP 1889 EP 1891 DI 10.1056/NEJMp078163 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 228LX UT WOS:000250732500003 PM 17989381 ER PT J AU Samuels, MA Gonzalez, RG Kim, AY Stemmer-Rachamimov, A AF Samuels, Martin A. Gonzalez, R. Gilberto Kim, Arthur Y. Stemmer-Rachamimov, Anat TI A 77-year-old man with ear pain, difficulty speaking, and altered mental status SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CEREBROSPINAL-FLUID OTORRHEA; BACTERIAL-MENINGITIS; ARACHNOID GRANULATIONS; CLINICAL-FEATURES; ADULTS; MANAGEMENT; THROMBOSIS; SINUSES C1 Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Infect Dis, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Neurol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Radiol, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Med, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. RP Samuels, MA (reprint author), Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. NR 20 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 8 PY 2007 VL 357 IS 19 BP 1957 EP 1965 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 228LX UT WOS:000250732500013 PM 17989389 ER PT J AU McMurray, JJV Teerlink, JR Cotter, G Bourge, RC Cleland, JGF Jondeau, G Krum, H Metra, M O'Connor, CM Parker, JD Torre-Amione, G van Veldhuisen, DJ Lewsey, J Frey, A Rainisio, M Kobrin, I AF McMurray, John J. V. Teerlink, John R. Cotter, Gadi Bourge, Robert C. Cleland, John G. F. Jondeau, Guillaume Krum, Henry Metra, Marco O'Connor, Christopher M. Parker, John D. Torre-Amione, Guillermo van Veldhuisen, Dirk J. Lewsey, Jim Frey, Aline Rainisio, Maurizio Kobrin, Isaac CA VERITAS Investigators TI Effects of tezosentan on symptoms and clinical outcomes in patients with acute heart failure - The VERITAS Randomized controlled trials SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID ENDOTHELIN RECEPTOR ANTAGONIST; COLLEGE-OF-CARDIOLOGY; DOUBLE-BLIND; INTRAVENOUS TEZOSENTAN; SCIENTIFIC SESSIONS; BIG ENDOTHELIN-1; NESIRITIDE; UPDATE; LEVOSIMENDAN; MULTICENTER AB Context Plasma concentrations of the vasoconstrictor peptide endothelin-1 are increased in patients with heart failure, and higher concentrations are associated with worse outcomes. Tezosentan is an intravenous short-acting endothelin receptor antagonist that has favorable hemodynamic actions in heart failure. Objective To determine if tezosentan improves outcomes in patients with acute heart failure. Design, Setting, and Participants The Value of Endothelin Receptor Inhibition With Tezosentan in Acute Heart Failure Studies, 2 independent, identical, and concurrent randomized, double-blind, placebo-controlled, parallel-group trials conducted from April 2003 through January 2005 at sites in Australia, Europe, Israel, and North America. Patients admitted within the previous 24 hours with persisting dyspnea and a respiratory rate of 24/min or greater were eligible provided they fulfilled 2 of 4 criteria: (1) elevated plasma concentrations of B-type or N-terminal pro-B-type natriuretic peptide, (2) clinical pulmonary edema, (3) radiologic pulmonary congestion or edema, or (4) left ventricular systolic dysfunction. Intervention Infusion of tezosentan (5 mg/h for 30 minutes, followed by 1 mg/h for 24 to 72 hours [n = 730]) or placebo (n = 718). Main Outcome Measures The coprimary end points were change in dyspnea (measured at 3, 6, and 24 hours using a visual analog scale from 0-100) over 24 hours (as area under the curve) in the individual trials and incidence of death or worsening heart failure at 7 days in both trials combined. Results Of the 1435 patients who received treatment as assigned, 855 (60%) were men; mean age was 70 years. Mean left ventricular ejection fraction (measured in 779 patients [54%]) was 29% (SD, 11%). Baseline dyspnea scores were similar in the 2 treatment groups. Tezosentan did not improve dyspnea more than placebo in either trial, with a mean treatment difference of -12 (95% confidence interval [CI], -105 to 81) mm . h (P = .80) in the first trial and -25 (95% CI, -119 to 69) mm . h (P = .60) in the second. The incidence of death or worsening heart failure at 7 days in the combined trials was 26% in each treatment group (odds ratio, 0.99; 95% confidence interval, 0.82-1.21; P = .95). Conclusion The endothelin receptor antagonist tezosentan did not improve symptoms or clinical outcomes in patients with acute heart failure. C1 Univ Glasgow, Western Infirm, Dept Cardiol, Glasgow G12 8QQ, Lanark, Scotland. San Francisco VA Med Ctr, Cardiol Sect, San Francisco, CA USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Duke Univ, Med Ctr, Dept Med, Div Cardiol, Durham, NC 27710 USA. Duke Clin Res Inst, Durham, NC USA. Univ Alabama, Dept Med, Birmingham, AL 35294 USA. Univ Hull, Castlehill Hosp, Dept Cardiol, Kingston Upon Hull HU6 7RX, N Humberside, England. Hop Ambroise Pare, Dept Cardiol, Boulogne, France. Monash Univ, Cent & Eastern Clin Sch, Dept Med, Melbourne, Vic 3004, Australia. Monash Univ, Cent & Eastern Clin Sch, Dept Epidemiol, Melbourne, Vic 3004, Australia. Monash Univ, Cent & Eastern Clin Sch, Dept Cardiol, Melbourne, Vic 3004, Australia. Univ Brescia, Dept Expt & Appl Med, Sect Cardiovasc Dis, Brescia, Italy. Mt Sinai & Univ Hlth Network Hosp, Toronto, ON, Canada. Baylor Coll Med, Winters Ctr Heart Failure Res, Methodist DeBakey Heart Ctr, Houston, TX 77030 USA. Univ Groningen Hosp, Ctr Thorax, Dept Cardiol, Groningen, Netherlands. Univ Glasgow, Dept Publ Hlth & Hlth Policy, Glasgow, Lanark, Scotland. Actelion Pharmaceut Ltd, Allschwil, Switzerland. RP McMurray, JJV (reprint author), Univ Glasgow, Western Infirm, Dept Cardiol, Glasgow G12 8QQ, Lanark, Scotland. EM j.mcmurray@bio.gla.ac.uk RI Lewsey, James/F-7546-2010; Teerlink, John/D-2986-2012; van Veldhuisen, Dirk Jan/E-8967-2014; OI Cleland, John/0000-0002-1471-7016; Parker, John/0000-0003-1949-2669; Metra, Marco/0000-0001-6691-8568; mcmurray, john/0000-0002-6317-3975 NR 33 TC 187 Z9 191 U1 0 U2 11 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 7 PY 2007 VL 298 IS 17 BP 2009 EP 2019 DI 10.1001/jama.298.17.2009 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 228GP UT WOS:000250718200021 PM 17986694 ER PT J AU Alley, DE Chang, VW AF Alley, Dawn E. Chang, Virginia W. TI The changing relationship of obesity and disability, 1988-2004 SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID BODY-MASS-INDEX; OLD-AGE DISABILITY; UNITED-STATES; RISK-FACTORS; US ADULTS; TRENDS; PREVALENCE; OVERWEIGHT; MORTALITY; HEALTH AB Context Recent studies suggest that the obese population may have been growing healthier since the 1960s, as indicated by a decrease in mortality and cardiovascular risk factors. However, whether these improvements have conferred decreased risk for disability is unknown. The obese population may be living longer with better-controlled risk factors but paradoxically experiencing more disability. Objective To determine whether the association between obesity and disability has changed over time. Design, Setting, and Participants Adults aged 60 years and older (N = 9928) with measured body mass index from 2 waves of the nationally representative National Health and Nutrition Examination Surveys (NHANES III [1988-1994] and NHANES 19992004). Main Outcome Measures Reports of much difficulty or inability to perform tasks in 2 disability domains: functional limitations (walking one-fourth mile, walking up 10 steps, stooping, lifting 10 lb, walking between rooms, and standing from an armless chair) and activities of daily living (ADL) limitations (transferring, eating, and dressing). Results Among obese individuals, the prevalence of functional impairment increased 5.4% (from 36.8%-42.2%; P = .03) between the 2 surveys, and ADL impairment did not change. At time 1 (1988-1994), the odds of functional impairment for obese individuals were 1.78 times greater than for normal-weight individuals (95% confidence interval [CI], 1.47-2.16). At time 2 (1999-2004), this odds ratio increased to 2.75 (95% CI, 2.39-3.17), because the odds of functional impairment increased by 43% (OR 1.43; 95% CI, 1.18-1.75) among obese individuals during this period, but did not change among nonobese individuals. With respect to ADL impairment, odds for obese individuals were not significantly greater than for individuals with normal weight (OR, 1.31; 95% CI, 0.92-1.88) at time 1, but increased to 2.05 (95% CI, 1.45-2.88) at time 2. This was because the odds of ADL impairment did not change for obese individuals but decreased by 34% among nonobese individuals (OR, 0.66; 95% CI, 0.50-0.88). Conclusions Recent cardiovascular improvements have not been accompanied by reduced disability within the obese older population. Rather, obese participants surveyed during 1999-2004 were more likely to report functional impairments than obese participants surveyed during 1988-1994, and reductions in ADL impairment observed for nonobese older individuals did not occur in those who were obese. Over time, declines in obesity-related mortality, along with a younger age at onset of obesity, could lead to an increased burden of disability within the obese older population. C1 Univ Penn, Robert Wood Johnson Hlth & Soc Scholars Program, Philadelphia, PA 19104 USA. Univ Penn, Philadelphia Vet Affairs Med Ctr, Dept Med,Sch Med, Dept Sociol, Philadelphia, PA 19104 USA. RP Alley, DE (reprint author), Univ Penn, Robert Wood Johnson Hlth & Soc Scholars Program, 3641 Locust Walk,Ste 302, Philadelphia, PA 19104 USA. EM alley@wharton.upenn.edu FU NICHD NIH HHS [K12-HD043459] NR 32 TC 227 Z9 228 U1 3 U2 8 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 7 PY 2007 VL 298 IS 17 BP 2020 EP 2027 DI 10.1001/jama.298.17.2020 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 228GP UT WOS:000250718200022 PM 17986695 ER PT J AU Azmandian, F Kaeli, D Dy, JG Hutchinson, E Ancukiewicz, M Niemierko, A Jiang, SB AF Azmandian, Fatemeh Kaeli, David Dy, Jennifer G. Hutchinson, Elizabeth Ancukiewicz, Marek Niemierko, Andrzej Jiang, Steve B. TI Towards the development of an error checker for radiotherapy treatment plans: a preliminary study SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID RADIATION TREATMENT; QUALITY-ASSURANCE; INCIDENTS; DELIVERY AB Major accidents can happen during radiotherapy, with an extremely severe consequence to both patients and clinical professionals. We propose to use machine learning and data mining techniques to help detect large human errors in a radiotherapy treatment plan, as a complement to human inspection. One such technique is computer clustering. The basic idea of using clustering algorithms for outlier detection is to first cluster (based on the treatment parameters) a large number of patient treatment plans. Then, when checking a new treatment plan, the parameters of the plan will be tested to see whether or not they belong to the established clusters. If not, they will be considered as 'outliers' and therefore highlighted to catch the attention of the human chart checkers. As a preliminary study, we applied the K-means clustering algorithm to a simple patient model, i.e., 'four-field' box prostate treatment. One thousand plans were used to build the clusters while another 650 plans were used to test the proposed method. It was found that there are eight distinct clusters. At the error levels of +/-100% of the original values of the monitor unit, the detection rate is about 100%. At +/-50% error level, the detection rate is about 80%. The false positive rate is about 10%. When purposely changing the beam energy to a value different from that in the treatment plan, the detection rate is 100% for posterior, right-lateral and left-lateral fields, and about 77% for the anterior field. This preliminary work has shown promise for developing the proposed automatic outlier detection software, although more efforts will still be required. C1 Northeastern Univ, Dept Elect & Comp Engn, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Univ Calif San Diego, Dept Radiat Oncol, La Jolla, CA 92093 USA. RP Azmandian, F (reprint author), Northeastern Univ, Dept Elect & Comp Engn, Boston, MA 02115 USA. EM sbjiang@ucsd.edu NR 26 TC 5 Z9 6 U1 0 U2 3 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 2007 VL 52 IS 21 BP 6511 EP 6524 DI 10.1088/0031-9155/52/21/012 PG 14 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 224JO UT WOS:000250443500012 PM 17951859 ER PT J AU Qaseem, A Snow, V Shekelle, P Sherif, K Wilt, TJ Weinberger, S Owens, DK AF Qaseem, Amir Snow, Vincenza Shekelle, Paul Sherif, Katherine Wilt, Timothy J. Weinberger, Steven Owens, Douglas K. CA C E A S A C P TI Diagnosis and management of stable chronic obstructive pulmonary disease: A clinical practice guideline from the American college of physicians SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; INHALED ANTICHOLINERGIC BRONCHODILATOR; LOW LUNG-FUNCTION; FLUTICASONE PROPIONATE; OXYGEN-THERAPY; MEDICAL HISTORY; HEALTH OUTCOMES; BETA-AGONISTS; AIR-FLOW; COPD AB Recommendation 1: In patients with respiratory symptoms, particularly dyspnea, spirometry should be performed to diagnose airflow obstruction. Spirometry should not be used to screen for airflow obstruction in asymptomatic individuals. (Grade: strong recommendation, moderate-quality evidence.) Recommendation 2: Treatment for stable chronic obstructive pulmonary disease (COPD) should be reserved for patients who have respiratory symptoms and FEV1 less than 60% predicted, as documented by spirometry. (Grade: strong recommendation, moderate-quality evidence.) Recommendation 3: Clinicians should prescribe 1 of the following maintenance monotherapies for symptomatic patients with COPD and FEV1 less than 60% predicted: long-acting inhaled beta-agonists, long-acting inhaled anticholinergics, or inhaled corticosteroids. (Grade: strong recommendation, high-quality evidence.) Recommendation 4: Clinicians may consider combination inhaled therapies for symptomatic patients with COPD and FEV1 less than 60% predicted. (Grade: weak recommendation, moderate-quality evidence.) Recommendation 5: Clinicians should prescribe oxygen therapy in patients with COPD and resting hypoxemia (Pao(2) <= 55 mm Hg). (Grade: strong recommendation, moderate-quality evidence.) Recommendation 6: Clinicians should consider prescribing pulmonary rehabilitation in symptomatic individuals with COPD who have an FEV1 less than 50% predicted. (Grade: weak recommendation, moderate-quality evidence.) C1 Amer Coll Physicians, Philadelphia, PA 19106 USA. Drexel Univ, Coll Med, Philadelphia, PA 19104 USA. Vet Affairs Greater Los Angeles Healthcare Syst, Santa Monica, CA USA. RAND, Santa Monica, CA USA. Vet Affairs Palo Alto Hlth Care Syst, Stanford, CA USA. Stanford Univ, Stanford, CA 94305 USA. Minnesota Vet Affairs Med Ctr, Minneapolis, MN USA. RP Qaseem, A (reprint author), Amer Coll Physicians, 190 N Independence Mall W, Philadelphia, PA 19106 USA. EM aqaseem@acponline.org NR 52 TC 115 Z9 120 U1 1 U2 6 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 6 PY 2007 VL 147 IS 9 BP 633 EP 638 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 227QM UT WOS:000250672900006 PM 17975186 ER PT J AU Smith, WR Betancourt, JR Wynia, MK Bussey-Jones, J Stone, VE Phillips, CO Fernandez, A Jacobs, E Bowles, J AF Smith, Wally R. Betancourt, Joseph R. Wynia, Matthew K. Bussey-Jones, Jada Stone, Valerie E. Phillips, Christopher O. Fernandez, Alicia Jacobs, Elizabeth Bowles, Jacqueline TI Recommendations for teaching about racial and ethnic disparities in health and health care SO ANNALS OF INTERNAL MEDICINE LA English DT Review ID CORONARY HEART-DISEASE; CROSS-CULTURAL CARE; PATIENT PREFERENCES; UNITED-STATES; CARDIAC-CATHETERIZATION; MEDICAL-CARE; RACE; PHYSICIANS; COMPETENCE; EDUCATION AB Racial and ethnic minorities often receive lower-quality health care than white patients, even when socioeconomic status, education, access, and other factors are used as controls. To address these pervasive disparities, health care professionals should learn more about them and the roles they can play in eliminating them, but few curricula are focused on understanding and addressing racial and ethnic health disparities, and well-accepted guidelines on what and how to teach in this complex area are lacking. The Society of General Internal Medicine Health Disparities Task Force used a review and consensus process to develop specific recommendations and guidelines for curricula focusing on health disparities. Learning objectives, content, methods for teaching, and useful resources are provided. Although the guidelines were developed primarily for teaching medical students, residents, and practitioners in primary care, the Task Force's general recommendations can apply to learners in any specialty. The Task Force recommends that a curricula address 3 areas of racial and ethnic health disparities and focus on the following specific learning objectives: 1) examining and understanding attitudes, such as mistrust, subconscious bias, and stereotyping, which practitioners and patients may bring to clinical encounters; 2) gaining knowledge of the existence and magnitude of health disparities, including the multifactorial causes of health disparities and the many solutions required to diminish or eliminate them; and 3) acquiring the skills to effectively communicate and negotiate across cultures, languages, and literacy levels, including the use of key tools to improve communication. The broad goal of a curriculum on disparities should be for learners to develop a commitment to eliminating inequities in health care quality by understanding and assuming their professional role in addressing this pressing health care crisis. C1 Virginia Commonwealth Univ, Ctr Hlth Dispar, Div Qual Hlth Care, Richmond, VA 23298 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Amer Med Assoc, Inst Eth, Chicago, IL 60610 USA. Stronger Hosp Cook County, Chicago, IL USA. Rush Univ, Med Ctr, Chicago, IL 60612 USA. Emory Univ, Sch Med, Atlanta, GA USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. San Francisco Gen Hosp, San Francisco, CA 94110 USA. Sepulveda Ambulatory Care Ctr, North Hills, CA USA. RP Smith, WR (reprint author), Virginia Commonwealth Univ, Ctr Hlth Dispar, Div Qual Hlth Care, Box 980306,1200 E Broad St,Room W10W-402, Richmond, VA 23298 USA. NR 119 TC 81 Z9 82 U1 10 U2 32 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 6 PY 2007 VL 147 IS 9 BP 654 EP 665 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 227QM UT WOS:000250672900008 PM 17975188 ER PT J AU Cannon, CP Husted, S Harrington, RA Scirica, BM Emanuelsson, H Storey, RF AF Cannon, Christopher P. Husted, Steen Harrington, Robert A. Scirica, Benjamin M. Emanuelsson, Hakan Storey, Robert F. CA DISPERSE-2 Invest TI Safety, tolerability, and initial efficacy of AZD6140, the first reversivle oral adenosine diphosphate receptor antagonist, compared with clopidigrel, in patients with non-ST-segment elevation acute coronary syndrome - Primary results of the DISPERSE-2 trial SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; CLOPIDOGREL RESISTANCE; ASPIRIN; INTERVENTION; PHARMACOLOGY; PRETREATMENT; THERAPY; EVENTS; HEART; RISK AB Objectives Our goal was to compare the safety and initial efficacy of AZD6140, the first reversible oral adenosine diphosphate receptor antagonist, with clopidogrel in patients with non-ST-segment elevation acute coronary syndromes, (NSTE-ACS). Background AZD6140 achieves higher mean levels of platelet inhibition than clopidogrel in patients with stable coronary artery disease. Methods A total of 990 patients with NSTE-ACS, treated with aspirin and standard therapy for ACS, were randomized in a 1:1:1 double-blind fashion to receive either twice-daily AZD6140 90 mg, AZD6140 180 mg, or clopidogrel 300-mg loading dose plus 75 mg once daily for up to 12 weeks. Results The primary end point, the Kaplan-Meier rate of major or minor bleeding through 4 weeks, was 8.1% in the clopidogrel group, 9.8% in the AZD6140 90-mg group, and 8.0% in the AZD6140 180-mg group (p = 0.43 and p = 0.96, respectively, vs. clopidogrel); the major bleeding rates were 6.9%, 7.1%, and 5.1%, respectively (p = 0.91 and p = 0.35, respectively, vs. clopidogrel). Although not statistically significant, favorable trends were seen in the Kaplan-Meier rates of myocardial infarction (MI) over the entire study period (MI: 5.6%, 3.8%, and 2.5%, respectively; p = 0.41 and p = 0.06, respectively, vs. clopidogrel). In a post-hoc analysis of continuous electrocardiograms, mostly asymptomatic ventricular pauses > 2.5 s were more common, especially in the AZD6140 180-mg group (4.3%, 5.5%, and 9.9%, respectively; p = 0.58 and p = 0.01, respectively, vs. clopidogrel). Conclusions This initial experience with AZD6140 in patients with ACS showed no difference in major bleeding but an increase in minor bleeding at the higher dose with encouraging results on the secondary end point of MI. This agent is currently being studied in a large outcomes trial in 18,000 patients with ACS. C1 Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Arhus Univ Hosp, Aarhus, Denmark. Duke Clin Res Inst, Durham, NC USA. AstraZeneca, Molndal, Sweden. AstraZeneca, Wilmington, DE USA. Univ Sheffield, Sheffield, S Yorkshire, England. RP Cannon, CP (reprint author), Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. EM cpcannon@partners.org NR 18 TC 301 Z9 320 U1 1 U2 18 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 6 PY 2007 VL 50 IS 19 BP 1844 EP 1851 DI 10.1016/j.jacc.2007.07.053 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 229FK UT WOS:000250788300005 PM 17980250 ER PT J AU Storey, RF Husted, S Harrington, RA Heptinstall, S Wilcox, RG Peters, G Wickens, M Emanuelsson, H Gurbel, P Grande, P Cannon, CP AF Storey, Robert F. Husted, Steen Harrington, Robert A. Heptinstall, Stanley Wilcox, Robert G. Peters, Gary Wickens, Mark Emanuelsson, Hakan Gurbel, Paul Grande, Peer Cannon, Christopher P. TI Inhibition of platelet aggregation by AZD6140, A reversible oral P2Y(12) receptor antagonist, compared with clopidogral in patients with acute coronary syndrome SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID ST-SEGMENT ELEVATION; MYOCARDIAL-INFARCTION; STENT THROMBOSIS; RESISTANCE; REACTIVITY; ASPIRIN; RISK AB Objectives In a substudy of DISPERSE (Dose confirmation Study assessing anti-Platelet Effects of AZD6140 vs. clopidogRel in non-ST-segment Elevation myocardial infarction)-2, we compared the antiplatelet effects of AZD6140 and clopidogrel and assessed the effects of AZD6140 in clopidogrel-pretreated patients. Background Clopidogrel, in combination with aspirin, reduces cardiovascular events in patients with acute coronary syndromes (ACS). However, patients with poor inhibition of platelet aggregation with clopidogrel may be less well protected. AZD6140 is a reversible oral P2Y(12) receptor antagonist that has been studied in ACS patients in comparison with clopidogrel (DISPERSE-2 study). Methods Patients were randomized to receive either AZD6140 90 mg twice a day, AZD6140 180 mg twice a day, or clopidogrel 75 mg once a day for up to 12 weeks in a double-blind, double-dummy design. One-half the patients allocated AZD6140 received a 270-mg loading dose. Patients randomized to receive clopidogrel were given a 300-mg loading dose unless they had already been treated with clopidogrel. Adenosine diphosphate-induced platelet aggregation was assessed by optical aggregometry on day 1 and at 4-week intervals. Results AZD6140 inhibited platelet aggregation in a dose-dependent fashion and both doses achieved greater levels of inhibition than clopidogrel (e.g., 4 weeks, 4-h postdose [mean (+/- SD)]: clopidogrel 64% [+/- 22%], AZD6140 90 mg 79% [+/- 22%], AZD6140 180 mg 95% [+/- 8%]. AZD6140 also produced further suppression of platelet aggregation in patients previously treated with clopidogrel. Conclusions AZD6140 exhibited greater mean inhibition of platelet aggregation than a standard regimen of clopidogrel in ACS patients. In addition, AZD6140 further suppressed platelet aggregation in clopidogrel pretreated patients. C1 Univ Sheffield, Sch Med & Biomed Sci, Cardiovasc Res Unit, Sheffield S10 2RX, S Yorkshire, England. Arhus Univ Hosp, Dept Med & Cardiol, Aarhus, Denmark. Duke Clin Res Inst, Div Cardiovasc Dis, Durham, NC USA. Univ Nottingham, Nottingham NG7 2RD, England. AstraZeneca R&D, Wilmington, DE USA. AstraZeneca R&D, Molndal, Sweden. Sinai Ctr Thrombosis Res, Baltimore, MD USA. Copenhagen Univ Hosp, Rigshosp, Dept Cardiol, Copenhagen, Denmark. Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Storey, RF (reprint author), Univ Sheffield, Sch Med & Biomed Sci, Cardiovasc Res Unit, Beech Hill Rd, Sheffield S10 2RX, S Yorkshire, England. EM r.f.storey@sheffield.ac.uk NR 14 TC 253 Z9 261 U1 0 U2 6 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 6 PY 2007 VL 50 IS 19 BP 1852 EP 1856 DI 10.1016/j.jacc.2007.07.058 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 229FK UT WOS:000250788300006 PM 17980251 ER PT J AU Mielke, MM Rosenberg, PB Tschanz, J Cook, L Corcoran, C Hayden, KM Norton, M Rabins, PV Green, RC Welsh-Bohmer, KA Breitner, JCS Munger, R Lyketsos, CG AF Mielke, M. M. Rosenberg, P. B. Tschanz, J. Cook, L. Corcoran, C. Hayden, K. M. Norton, M. Rabins, P. V. Green, R. C. Welsh-Bohmer, K. A. Breitner, J. C. S. Munger, R. Lyketsos, C. G. TI Vascular factors predict rate of progression in Alzheimer disease SO NEUROLOGY LA English DT Article ID E EPSILON-4 ALLELE; CACHE COUNTY; DIABETES-MELLITUS; TOTAL CHOLESTEROL; APOLIPOPROTEIN-E; BLOOD-PRESSURE; RISK-FACTORS; COGNITIVE DECLINE; DEMENTIA; POPULATION AB Background: While there is considerable epidemiologic evidence that cardiovascular risk factors increase risk of incident Alzheimer disease ( AD), few studies have examined their effect on progression after an established AD diagnosis. Objective: To examine the effect of vascular factors, and potential age modification, on rate of progression in a longitudinal study of incident dementia. Methods: A total of 135 individuals with incident AD, identified in a population-based sample of elderly persons in Cache County, UT, were followed with in-home visits for a mean of 3.0 years ( range: 0.8 to 9.5) and 2.1 follow-up visits ( range: 1 to 5). The Clinical Dementia Rating ( CDR) Scale and Mini-Mental State Examination ( MMSE) were administered at each visit. Baseline vascular factors were determined by interview and physical examination. Generalized least-squares random-effects regression was performed with CDR Sum of Boxes ( CDR-Sum) or MMSE as the outcome, and vascular index or individual vascular factors as independent variables. Results: Atrial fibrillation, systolic hypertension, and angina were associated with more rapid decline on both the CDR-Sum and MMSE, while history of coronary artery bypass graft surgery, diabetes, and antihypertensive medications were associated with a slower rate of decline. There was an age interaction such that systolic hypertension, angina, and myocardial infarction were associated with greater decline with increasing baseline age. Conclusion: Atrial fibrillation, hypertension, and angina were associated with a greater rate of decline and may represent modifiable risk factors for secondary prevention in Alzheimer disease. The attenuated decline for diabetes and coronary artery bypass graft surgery may be due to selective survival. Some of these effects appear to vary with age. C1 Johns Hopkins Univ Sch Med, Dept Psychiat, Div Geriatr Psychiat & Behav Sci, Baltimore, MD 21205 USA. Utah State Univ, Logan, UT 84322 USA. Duke Univ, Med Ctr, Durham, NC USA. Boston Univ, Sch Med, Boston, MA 02215 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Washington, Sch Med, Seattle, WA USA. RP Mielke, MM (reprint author), Johns Hopkins Univ Sch Med, Dept Psychiat, Div Geriatr Psychiat & Behav Sci, 550 N Broadway,Suite 308, Baltimore, MD 21205 USA. EM mmielke1@jhmi.edu RI Corcoran, Chris/F-2155-2010; Tschanz, JoAnn/E-5986-2010; Hayden, Kathleen/B-6442-2012 OI Hayden, Kathleen/0000-0002-7745-3513 FU NCRR NIH HHS [M01 RR000533]; NIA NIH HHS [P01 AG05146, R01 AG011380, R01 AG11380, R01 AG18712, R01 AG21136] NR 41 TC 173 Z9 178 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD NOV 6 PY 2007 VL 69 IS 19 BP 1850 EP 1858 DI 10.1212/01.wnl.0000279520.59792.fe PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 228CH UT WOS:000250704200008 PM 17984453 ER PT J AU Xu, Q Majumder, PK Ross, K Shim, Y Golub, TR Loda, M Sellers, WR AF Xu, Qing Majumder, Pradip K. Ross, Kenneth Shim, Yeonju Golub, Todd R. Loda, Massimo Sellers, William R. TI Identification of prostate cancer modifier pathways using parental strain expression mapping SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE glycolysis; proliferation ID GENE-EXPRESSION; INTRAEPITHELIAL NEOPLASIA; PATTERNS; BEHAVIOR; MODEL AB Inherited genetic risk factors play an important role in cancer. However, other than the Mendelian fashion cancer susceptibility genes found in familial cancer syndromes, little is known about risk modifiers that control individual susceptibility. Here we developed a strategy, parental strain expression mapping, that utilizes the homogeneity of inbred mice and genome-wide mRNA expression analyses to directly identify candidate germ-line modifier genes and pathways underlying phenotypic differences among murine strains exposed to transgenic activation of AKT1. We identified multiple candidate modifier pathways and, specifically, the glycolysis pathway as a candidate negative modulator of AKT1-induced proliferation. in keeping with the findings in the murine models, in multiple human prostate expression data set, we found that enrichment of glycolysis pathways in normal tissues was associated with decreased rates of cancer recurrence after prostatectomy. Together, these data suggest that parental strain expression mapping can directly identify germline modifier pathways of relevance to human disease. C1 Novartis Inst Biomed Res, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Broad Inst, Cambridge, MA 02141 USA. MIT, Cambridge, MA 02141 USA. RP Sellers, WR (reprint author), Novartis Inst Biomed Res, 250 Massachusetts Ave,4A-245, Cambridge, MA 02139 USA. EM william.sellers@novartis.com FU NCI NIH HHS [P01 CA089021] NR 25 TC 9 Z9 9 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD NOV 6 PY 2007 VL 104 IS 45 BP 17771 EP 17776 DI 10.1073/pnas.0708476104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 230TA UT WOS:000250897600042 PM 17978178 ER PT J AU Ganem, NJ Pellman, D AF Ganem, Neil J. Pellman, David TI Limiting the proliferation of polyploid cells SO CELL LA English DT Article ID MAMMALIAN-CELLS; CYCLE PROGRESSION; TETRAPLOIDY; ANEUPLOIDY; CHECKPOINTS; INHIBITION; DIVISION; FAILURE; CANCER; ARREST AB Many errors in cell division lead to failure of cytokinesis and the generation of tetraploid cells. Given that tetraploidy can have deleterious consequences, such as genetic instability, we discuss the mechanisms that may have evolved to directly or indirectly prevent the proliferation of these cells. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Dept Pediat Hematol Oncol, Boston, MA 02115 USA. RP Pellman, D (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. EM david_pellman@dfci.harvard.edu NR 22 TC 83 Z9 84 U1 0 U2 5 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD NOV 2 PY 2007 VL 131 IS 3 BP 437 EP 440 DI 10.1016/j.cell.2007.10.024 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 226WF UT WOS:000250618500008 PM 17981108 ER PT J AU Jain, RK Xu, L AF Jain, Rakesh K. Xu, Lei TI alpha PIGF: A new kid on the antiangiogenesis block SO CELL LA English DT Editorial Material ID VASCULAR-PERMEABILITY FACTOR; ENDOTHELIAL GROWTH-FACTOR; ANGIOGENESIS; CANCER; BEVACIZUMAB; INHIBITION; DISCOVERY; CARCINOMA; RECEPTOR; THERAPY AB An agent that blocks tumor angiogenesis, growth, and metastasis without affecting normal tissues-whether used alone or in combination with currently approved drugs-would change the way we treat cancer. In this issue, Fischer et al. (2007) offer compelling evidence that a monoclonal antibody against placental growth factor (PIGF), a member of the VEGF family, has such potential in mice. C1 Massachusetts Gen Hosp, Dept Radiat Oncol, Steele Lab Turnor Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Jain, RK (reprint author), Massachusetts Gen Hosp, Dept Radiat Oncol, Steele Lab Turnor Biol, Boston, MA 02114 USA. EM jain@steele.mgh.harvard.edu NR 12 TC 19 Z9 20 U1 0 U2 3 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD NOV 2 PY 2007 VL 131 IS 3 BP 443 EP 445 DI 10.1016/j.cell.2007.10.023 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 226WF UT WOS:000250618500010 PM 17981110 ER PT J AU Pospisilik, JA Knauf, C Joza, N Benit, P Orthofer, M Cani, PD Ebersberger, I Nakashima, T Sarao, R Neely, G Esterbauer, H Kozlov, A Kahn, CR Kroemer, G Rustin, P Burcelin, R Penninger, JM AF Pospisilik, J. Andrew Knauf, Claude Joza, Nicholas Benit, Paule Orthofer, Michael Cani, Patrice D. Ebersberger, Ingo Nakashima, Tomoki Sarao, Renu Neely, Gregory Esterbauer, Harald Kozlov, Andrey Kahn, C. Ronald Kroemer, Guido Rustin, Pierre Burcelin, Remy Penninger, Josef M. TI Targeted deletion of AIF decreases mitochondrial oxidative phosphorylation and protects from obesity and diabetes SO CELL LA English DT Article ID APOPTOSIS-INDUCING FACTOR; DNA GENE-EXPRESSION; INSULIN-RESISTANCE; DILATED CARDIOMYOPATHY; GLUCOSE-HOMEOSTASIS; SKELETAL-MUSCLE; DOWN-REGULATION; DUAL ROLES; DYSFUNCTION; PGC-1-ALPHA AB Type-2 diabetes results from the development of insulin resistance and a concomitant impairment of insulin secretion. Recent studies place altered mitochondrial oxidative phosphorylation (OxPhos) as an underlying genetic element of insulin resistance. However, the causative or compensatory nature of these OxPhos changes has yet to be proven. Here, we show that muscle-and liver-specific AIF ablation in mice initiates a pattern of OxPhos deficiency closely mimicking that of human insulin resistance, and contrary to current expectations, results in increased glucose tolerance, reduced fat mass, and increased insulin sensitivity. These results are maintained upon high-fat feeding and in both genetic mosaic and ubiquitous OxPhos-deficient mutants. Importantly, the effects of AIF on glucose metabolism are acutely inducible and reversible. These findings establish that tissue-specific as well as global OxPhos defects in mice can counteract the development of insulin resistance, diabetes, and obesity. C1 Austrian Acad Sci, Inst Mol Biotechnol, A-1030 Vienna, Austria. CHU Rangueil, IFR31, INSERM, U858,Equipe 2,Inst Med Mol Rangueil, F-31432 Toulouse, France. Hop Robert Debre, INSERM, U676, F-75019 Paris, France. Univ Catholique Louvain, Fac Med, Unit PMNT, B-1200 Brussels, Belgium. Max F Perutz Labs, Ctr Integrat Bioinformat Vienna, A-1030 Vienna, Austria. Med Univ Vienna, Clin Inst Med & Chem Lab Diagnost, Vienna, Austria. Lorenz Boehler Hosp, Ludwig Boltzmann Inst Clin & Expt Traumatol, Vienna, Austria. Harvard Univ, Sch Med, Dept Med, Joslin Diabet Ctr, Boston, MA 02215 USA. INSERM, U848, F-94805 Villejuif, France. Inst Gustave Roussy, F-94805 Villejuif, France. Univ Paris 11, F-94805 Villejuif, France. RP Penninger, JM (reprint author), Austrian Acad Sci, Inst Mol Biotechnol, Dr Bohrgasse 3, A-1030 Vienna, Austria. EM josef.penninger@imba.oeaw.ac.at RI neely, graham/A-6511-2011; Kroemer, Guido/B-4263-2013; Penninger, Josef/I-6860-2013; burcelin, remy/M-6013-2014; OI Penninger, Josef/0000-0002-8194-3777; Cani, Patrice D./0000-0003-2040-2448 FU NIDDK NIH HHS [DK31036] NR 40 TC 229 Z9 234 U1 2 U2 16 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD NOV 2 PY 2007 VL 131 IS 3 BP 476 EP 491 DI 10.1016/j.cell.2007.08.047 PG 16 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 226WF UT WOS:000250618500016 PM 17981116 ER PT J AU Wang, Y Rosen, H Madtes, DK Shao, B Martin, TR Heinecke, JW Fu, X AF Wang, Yi Rosen, Henry Madtes, David K. Shao, Baohai Martin, Thomas R. Heinecke, Jay W. Fu, Xiaoyun TI Myeloperoxidase inactivates TIMP-1 by oxidizing its N-terminal cysteine residue - An oxidative mechanism for regulating proteolysis during inflammation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RESPIRATORY-DISTRESS SYNDROME; MATRIX METALLOPROTEINASES; HYPOCHLOROUS ACID; TISSUE INHIBITOR; METHIONINE RESIDUES; HYDROGEN-PEROXIDE; PROTEINS; OXIDANTS; PEPTIDE; SYSTEM AB An imbalance between the proteolytic activity of matrix metalloproteinases (MMPs) and the activity of tissue inhibitors of metalloproteinases (TIMPs) is implicated in tissue injury during inflammation. The N-terminal cysteine of TIMP-1 plays a key role in the inhibitory activity of the protein because it coordinates the essential catalytic Zn2+ of the MMP, preventing the metal ion from functioning. An important mechanism for controlling the interaction of TIMPs with MMPs might involve hypochlorous acid (HOCl), a potent oxidant produced by the myeloperoxidase (MPO) system of phagocytes. Here, we show that HOCl generated by the MPO-H2O2-chloride system inactivates TIMP-1 by oxidizing its N-terminal cysteine. The product is a novel 2-oxo acid. Liquid chromatography-mass spectrometry and tandem mass spectrometry analyses demonstrated that methionine and N-terminal cysteine residues were rapidly oxidized by MPO-derived HOCl but only oxidation of the N-terminal cysteine of TIMP-1 correlated well with loss of inhibitory activity. Importantly, we detected the signature 2-oxo-acid N-terminal peptide in tryptic digests of bronchoalveolar lavage fluid from patients with acute respiratory distress syndrome, demonstrating that TIMP-1 oxidation occurs in vivo. Loss of the N-terminal amino group and disulfide structure are crucial for preventing TIMP-1 from inhibiting MMPs. Our findings suggest that pericellular production of HOCl by phagocytes is a pathogenic mechanism for impairing TIMP-1 activity during inflammation. C1 Univ Washington, Dept Med, Seattle, WA 98195 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. Vet Affairs Puget Sound Hlth Care Syst, Med Res Serv, Seattle, WA 98108 USA. RP Fu, X (reprint author), Univ Washington, Dept Med, Box 356426, Seattle, WA 98195 USA. EM xyfu@u.washington.edu RI Wang, Yi/C-2871-2013; OI Shao, Baohai/0000-0001-8832-2845 FU NHLBI NIH HHS [HL078527, HL063994, HL075381, P01 HL030086, P50 HL073996, P50HL073996, R01 HL063994, R01 HL075381, R01 HL078527]; NIEHS NIH HHS [P30 ES007033, P30ES07033] NR 51 TC 50 Z9 51 U1 2 U2 6 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 2 PY 2007 VL 282 IS 44 BP 31826 EP 31834 DI 10.1074/jbc.M704894200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 224WY UT WOS:000250480300002 PM 17726014 ER PT J AU Beyer, KS Beauchamp, RL Lee, MF Gusella, JF Naar, AM Ramesh, V AF Beyer, Kim S. Beauchamp, Roberta L. Lee, Ming-Fen Gusella, James F. Naar, Anders M. Ramesh, Vijaya TI Mediator subunit MED28 (magicin) is a repressor of smooth muscle cell differentiation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GENE EG-1; COMPLEX; TRANSCRIPTION; PROTEIN; IDENTIFICATION; COACTIVATORS; ACTIVATION; EXPRESSION; FAMILY AB Magicin, a protein that we isolated earlier as an interactor of the neurofibromatosis 2 protein merlin, was independently identified as MED28, a subunit of the mammalian Mediator complex. Mediator complex is an evolutionarily conserved transcriptional cofactor, which plays an essential role in positive and negative gene regulation. Distinct Mediator subunit composition is thought to contribute to gene regulation specificity based on the interaction of specific subunits with subsets of transcription factors. Here we report that down-regulation of Med28 expression in NIH3T3 cells results in a significant induction of several genes associated with smooth muscle cell ( SMC) differentiation. Conversely, overexpression of MED28 represses expression of SMC genes, in concordance with our knockdown data. More importantly, multipotent mesenchymal-derived murine precursors can transdifferentiate into SMCs when Med28 is down-regulated. Our data also show that Med28 functions as a negative regulator of SMC differentiation in concert with other Mediator subunits including Med6, Med8, and Med18 within the Mediator head module. Our results provide strong evidence that MED28 may function as a scaffolding protein by maintaining the stability of a submodule within the head module and that components of this submodule act together in a gene regulatory program to suppress SMC differentiation. The results presented here demonstrate for the first time that the mammalian Mediator subunit MED28 functions as a repressor of SMC differentiation, which could have implications for disorders associated with abnormalities in SMC growth and differentiation, including atherosclerosis, asthma, hypertension, and smooth muscle tumors. C1 Massachusetts Gen Hosp, Ctr Human Genet Res, Mol Neurogenet Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Cell Biol, Massachusetts Gen Hosp,Canc Ctr, Charlestown, MA 02129 USA. RP Ramesh, V (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Mol Neurogenet Unit, Simches Res Bldg,185 Cambridge ST, Boston, MA 02114 USA. EM ramesh@helix.mgh.harvard.edu FU NINDS NIH HHS [NS24279, NS45776] NR 28 TC 16 Z9 17 U1 8 U2 9 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 2 PY 2007 VL 282 IS 44 BP 32152 EP 32157 DI 10.1074/jbc.M706592200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 224WY UT WOS:000250480300037 PM 17848560 ER PT J AU Gibb, SL Boston-Howes, W Lavina, ZS Gustincich, S Brown, RH Pasinelli, P Trotti, D AF Gibb, Stuart L. Boston-Howes, William Lavina, Zeno S. Gustincich, Stefano Brown, Robert H., Jr. Pasinelli, Piera Trotti, Davide TI A caspase-3-cleaved fragment of the glial glutamate transporter EAAT2 is sumoylated and targeted to promyelocytic leukemia nuclear bodies in mutant SOD1-linked amyotrophic lateral sclerosis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MOTOR-NEURON DISEASE; SUMO-1 MODIFICATION; PROTEIN SUMOYLATION; 2-HYBRID SYSTEM; SPINAL-CORD; DNA-DAMAGE; PML BODIES; ALS; MICE; ACTIVATION AB EAAT2 (excitatory amino acid transporter 2) is a high affinity, Na+-dependent glutamate transporter of glial origin that is essential for the clearance of synaptically released glutamate and prevention of excitotoxicity. During the course of human amyotrophic lateral sclerosis (ALS) and in a transgenic mutant SOD1 mouse model of the disease, expression and activity of EAAT2 is remarkably reduced. We previously showed that some of the mutant SOD1 proteins exposed to oxidative stress inhibit EAAT2 by triggering caspase-3 cleavage of EAAT2 at a single defined locus. This gives rise to two fragments that we termed truncated EAAT2 and COOH terminus of EAAT2 (CTE). In this study, we report that analysis of spinal cord homogenates prepared from mutant G93A-SOD1 mice reveals CTE to be of a higher molecular weight than expected because it is conjugated with SUMO-1. The sumoylated CTE fragment (CTE-SUMO-1) accumulates in the spinal cord of these mice as early as presymptomatic stage(70 days of age) andnot in other central nervous system areas unaffected by the disease. The presence and accumulation of CTE-SUMO-1 is specific to ALS mice, since it does not occur in the R6/2 mouse model for Huntington disease. Furthermore, using an astroglial cell line, primary culture of astrocytes, and tissue samples from G93A-SOD1 mice, we show that CTE-SUMO-1 is targeted to promyelocytic leukemia nuclear bodies. Since one of the proposed functions of promyelocytic leukemia nuclear bodies is regulation of gene transcription, we suggest a possible novel mechanism by which the glial glutamate transporter EAAT2 could contribute to the pathology of ALS. C1 Thomas Jefferson Univ, Weinberg Unit ALS Res, Farber Inst Neurosci, Philadelphia, PA 19107 USA. Massachusetts Gen Hosp, Cecil B Day Lab Neuromuscular Res, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Giovanni Armenise Harvard Fdn Lab, Sector Neurobiol, Scuola Int Super Studi Avanzati, I-34012 Basovizza, Italy. RP Trotti, D (reprint author), Thomas Jefferson Univ, Weinberg Unit ALS Res, Farber Inst Neurosci, 900 Walnut St, Philadelphia, PA 19107 USA. EM davide.trotti@jefferson.edu FU NINDS NIH HHS [R01-NS44292]; Telethon [GGP06268] NR 63 TC 43 Z9 44 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 2 PY 2007 VL 282 IS 44 BP 32480 EP 32490 DI 10.1074/jbc.M704314200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 224WY UT WOS:000250480300071 PM 17823119 ER PT J AU Rowe, BH Diner, B Camargo, CA Worster, A Colacone, A Wyer, PC AF Rowe, Brian H. Diner, Barry Camargo, Carlos A., Jr. Worster, Andrew Colacone, Antoinette Wyer, Peter C. CA TCCT Ib Members TI Effective synthesized/preapprais ed evidence formats in emergency medicine and the use of supplemental knowledge translation techniques SO ACADEMIC EMERGENCY MEDICINE LA English DT Article; Proceedings Paper CT Consensus Conference on Knowledge Translation in Emergency Medicine CY MAY 15, 2007 CL Chicago, IL DE evidence-based medicine; preappraised evidence; audit and feedback; opinion leaders; reminders ID RANDOMIZED CONTROLLED-TRIALS; SYSTEMATIC REVIEWS; COCHRANE-LIBRARY; DISSEMINATION; INTERVENTIONS; METAANALYSES; RELEVANT; QUALITY; CARE AB Most clinicians, and especially emergency physicians, are increasingly faced with the need for valid and reliable evidence upon which to base practice decisions in a timely fashion. Despite the accumulation of synthesized evidence in emergency medicine over the past decade, knowledge gaps still exist between what is known and what is practiced. In many cases, this failure in knowledge uptake relates to barriers in uptake as well as the difficulty of translating evidence from research to the bedside. Preappraised evidence syntheses represent a potential partial solution to these problems by providing condensed summaries of the large volume of scientific literature in our field. The participants in this workshop examined the availability, utility, and impact of preappraised evidence and examined innovative ways to translate this knowledge into practice. In addition, the workshop participants also explored more globally all knowledge translation methods that are distinct from clinical pathways (e.g., audit and feedback, academic detailing, reminders, and local opinion leaders). These are initiatives that are instituted at the level of a particular hospital or with respect to a certain condition, and emergency physicians need to understand their definition and application. Overall, the recommendations arising from this workshop have the potential to alter future emergency care in important ways. C1 Univ Alberta, Edmonton, AB, Canada. Emory Univ, Atlanta, GA USA. Massachusetts Gen Hosp, Harvard Med Sch, Boston, MA USA. McMaster Univ, Hamilton, MT USA. Sir Mortimer B Davis Jewish Hosp, Montreal, PQ, Canada. Columbia Univ, New York, NY USA. RP Rowe, BH (reprint author), Univ Alberta, Edmonton, AB, Canada. EM browe@ualberta.ca NR 35 TC 5 Z9 5 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD NOV PY 2007 VL 14 IS 11 BP 1023 EP 1029 DI 10.1197/j.aem.2007.06.026 PG 7 WC Emergency Medicine SC Emergency Medicine GA 232AO UT WOS:000250990700020 PM 17967965 ER PT J AU Eusemann, CD Sammons, BE Holmes, DR Brady, TJ Erenburg, I Toneguzzo, F AF Eusemann, Christian D. Sammons, Barry E. Holmes, David R., III Brady, Thomas J. Erenburg, Irina Toneguzzo, Frances TI Academic technology transfer and radiology: A strong partnership for the future SO ACADEMIC RADIOLOGY LA English DT Article DE technology transfer; industry sponsored research; intellectual property AB To date, technology transfer from academia to industry has been strongest in the biotechnology and pharmaceutical sector. The medical imaging and medical device industries have traditionally been smaller players and, as a result, some, perhaps many, investigators in radiology are unaware of the potential value of technology transfer and the opportunity to receive sponsorship for research from medical imaging companies. Many investigators are also unaware of opportunities to introduce important academic discoveries into clinical practice through licensing and technology transfer. These untapped opportunities are not only valuable, but also are becoming more and more important in light of the ever-increasing difficulties associated with sustaining and receiving new government funding. The goal of this article is to provide academic scientists in the field of radiology with insights about the key aspects of the technology transfer process, including observations about inventions, intellectual property, and industry-sponsored research. C1 Partners Healthcare, Res Ventures & Licensing, Boston, MA 02199 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Mayo Clin, Rochester, MN 55905 USA. RP Toneguzzo, F (reprint author), Partners Healthcare, Res Ventures & Licensing, 101 Huntington Ave,4th Floor, Boston, MA 02199 USA. EM ftoneguzzo@partners.org NR 4 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD NOV PY 2007 VL 14 IS 11 BP 1289 EP 1295 DI 10.1016/j.acra.2007.09.003 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 229PR UT WOS:000250817000001 PM 17964453 ER PT J AU de Paz, LL Moseman, EA Noti, C Polito, L von Andrian, UH Seeberger, PH AF de Paz, Lose L. Moseman, E. Ashley Noti, Christian Polito, Laura von Andrian, Ulrich H. Seeberger, Peter H. TI Profiling heparin-chemokine interactions using synthetic tools SO ACS CHEMICAL BIOLOGY LA English DT Article ID SURFACE-PLASMON RESONANCE; CARBOHYDRATE MICROARRAYS; GLYCOSAMINOGLYCAN BINDING; HEPARIN/HEPARAN SULFATE; OLIGOSACCHARIDE MICROARRAYS; MODULAR SYNTHESIS; ANTITHROMBIN-III; LIGAND-BINDING; GROWTH-FACTORS; CXC CHEMOKINE AB Glycosaminoglycans (GAGs), such as heparin or heparan sulfate, are required for the in vivo function of chemokines. Chemokines play a crucial role in the recruitment of leukocyte subsets to sites of inflammation and lymphocytes trafficking. GAG-chemokine interactions mediate cell migration and determine which leukocyte subsets enter tissues. Identifying the exact GAC sequences that bind to particular chemokines is key to understand chemokine function at the molecular level and develop strategies to interfere with chemokine-mediated processes. Here, we characterize the heparin binding profiles of eight chemokines (CCL21, IL-8, CXCL12, CXCL13, CCL19, CCL25, CCL28, and CXCL16) by employing heparin microarrays containing a small library of synthetic heparin oligosaccharides. The chemokines differ significantly in their interactions with heparin oligosaccharides: While some chemokines, (e.g., CCL21) strongly bind to a hexasaccharide containing the GlcNSO3(6-OSO3)-IdoA(2-OSO3) repeating unit, CCL19 does not bind and CXCL12 binds only weakly. The carbohydrate microarray binding results were validated by surface plasmon resonance experiments. In vitro chemotaxis assays revealed that dendrimers coated with the fully sulfated heparin hexasaccharide inhibit lymphocyte migration toward CCL21. Migration toward CXCL12 or CCL19 was not affected. These in vitro homing assays indicate that multivalent synthetic heparin dendrimers inhibit the migration of lymphocytes toward certain chemokine gradients by blocking the formation of a chemokine concentration gradient on GAG enclothetial chains. These findings are in agreement with preliminary in vivo measurements of circulating lymphocytes. The results presented here contribute to the understanding of GAG-chemokine interactions, a first step toward the design of novel drugs that modulate chemokine activity. C1 Swiss Fed Inst Technol, Organ Chem Lab, CH-8093 Zurich, Switzerland. Harvard Univ, Sch Med, Dept Pathol, Ctr Blood Res, Boston, MA 02115 USA. RP Seeberger, PH (reprint author), Swiss Fed Inst Technol, Organ Chem Lab, Wolfgang Pauli Str 10,HCI F315, CH-8093 Zurich, Switzerland. EM seeberger@org.chem.ethz.ch RI Polito, Laura/C-4054-2009; von Andrian, Ulrich/A-5775-2008; de Paz, Jose L./H-1507-2015 OI Polito, Laura/0000-0002-7756-2365; de Paz, Jose L./0000-0002-8555-2271 FU NCI NIH HHS [P01 CA071932, P01 CA071932-11A2] NR 59 TC 25 Z9 25 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1554-8929 EI 1554-8937 J9 ACS CHEM BIOL JI ACS Chem. Biol. PD NOV PY 2007 VL 2 IS 11 BP 735 EP 744 DI 10.1021/cb700159m PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 233OO UT WOS:000251100400015 PM 18030990 ER PT J AU Ismail, H Wotring, M Kimmie, C Palmer, J Brooks-Worrell, B AF Ismail, H. Wotring, M. Kimmie, C. Palmer, J. Brooks-Worrell, B. TI "T cell-positive antibody-negative" phenotypic type 2 patients, a unique subgroup of autoimmune diabetes SO ACTA DIABETOLOGICA LA English DT Meeting Abstract C1 [Ismail, H.; Wotring, M.; Kimmie, C.; Palmer, J.; Brooks-Worrell, B.] Univ Washington, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0940-5429 J9 ACTA DIABETOL JI Acta Diabetol. PD NOV PY 2007 VL 44 SU 1 BP S24 EP S24 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 240WD UT WOS:000251618000077 ER PT J AU Tian, J Middleton, B Dang, H Von Boehmer, H Jaeckel, E Kaqman, DL AF Tian, J. Middleton, B. Dang, H. Von Boehmer, H. Jaeckel, E. Kaqman, D. L. TI Autoantigen tolerization can enhance autoreactivity to other beta-cell autoantigens SO ACTA DIABETOLOGICA LA English DT Meeting Abstract C1 [Tian, J.; Middleton, B.; Dang, H.; Kaqman, D. L.] Univ Calif Los Angeles, Los Angeles, CA USA. [Jaeckel, E.] Hannover Med Sch, Hannover, Germany. [Von Boehmer, H.] Dana Farber Canc Inst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0940-5429 J9 ACTA DIABETOL JI Acta Diabetol. PD NOV PY 2007 VL 44 SU 1 BP S26 EP S27 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 240WD UT WOS:000251618000085 ER PT J AU Ingelsson, M Ramasamy, K Russ, C Freeman, SH Orne, J Raju, S Matsui, T Growdon, JH Frosch, MP Ghetti, B Brown, RH Irizarry, MC Hyman, BT AF Ingelsson, Martin Ramasamy, Karunya Russ, Carsten Freeman, Stefanie H. Orne, Jennifer Raju, Susan Matsui, Toshifumi Growdon, John H. Frosch, Matthew P. Ghetti, Bernardino Brown, Robert H. Irizarry, Michael C. Hyman, Bradley T. TI Increase in the relative expression of tau with four microtubule binding repeat regions in frontotemporal lobar degeneration and progressive supranuclear palsy brains SO ACTA NEUROPATHOLOGICA LA English DT Article DE tau; alternative splicing; neurodegeneration; neuropathology ID APOLIPOPROTEIN-E EPSILON-4; ALZHEIMERS-DISEASE; CORTICOBASAL DEGENERATION; NEUROPATHOLOGIC CRITERIA; PICKS-DISEASE; PROTEIN-TAU; DEMENTIA; MUTATIONS; HAPLOTYPE; FTDP-17 AB Some cases of familial frontotemporal dementia (FTD) leading to frontotemporal lobar degeneration (FTLD) are caused by mutations in tau on chromosome 17 (FTDP-17). Certain mutations alter the ratio between four (4R tau) and three (3R tau) repeat tau isoforms whereas cases with progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) mainly have 4R tau brain pathology. We assessed tau mRNA and protein levels in frontal cortex from 15 sporadic FTLD, 21 PSP, 5 CBD, 15 Alzheimer's disease (AD) and 16 control brains. Moreover, we investigated the disease association and possible tau splicing effects of the tau H1 haplotype. Cases with FTLD and PSP had lower tau mRNA levels than control brains. When analyzing 4R tau and 3R tau mRNA separately, control subjects displayed a 4R tau/3R tau ratio of 0.48. Surprisingly, FTLD brains displayed a more elevated ratio (1.32) than PSP brains (1.12). Also, several FTLD and PSP cases had higher 4R tau/3R tau mRNA than FTDP-17 cases, included as reference tissues, and the ratio increase was seen regardless of underlying histopathology, i.e. both for tau-positive and tau-negative FTLD cases. Furthermore, total tau protein levels were slightly decreased in both FTLD and AD as compared to control subjects. Finally, we confirmed the association of tau H1 with PSP, but could not find any haplotype-related effect on tau exon 10 splicing. In conclusion, we demonstrated increased but largely variable 4R tau/3R tau mRNA ratios in FTLD and PSP cases, suggesting heterogeneous pathophysiological processes within these disorders. C1 Uppsala Univ, Dept Publ Hlth Mol Geriatr, S-75185 Uppsala, Sweden. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. Indiana Univ, Sch Med, Dept Pathol, Indianapolis, IN 46202 USA. RP Ingelsson, M (reprint author), Uppsala Univ, Dept Publ Hlth Mol Geriatr, Dag Hammarskjolds Vag 20, S-75185 Uppsala, Sweden. EM martin.ingelsson@pubcare.uu.se FU NIA NIH HHS [P30 AG10133, P50 AG05134, AG08487]; NIMH NIH HHS [R24-MH 068855] NR 37 TC 17 Z9 17 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 2007 VL 114 IS 5 BP 471 EP 479 DI 10.1007/s00401-007-0280-z PG 9 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 216YU UT WOS:000249915800003 PM 17721707 ER PT J AU Louis, DN Ohgaki, H Wiestler, OD Cavenee, WK Burger, PC Jouvet, A Scheithauer, BW Kleihues, P AF Louis, David N. Ohgaki, Hiroko Wiestler, Otmar D. Cavenee, Webster K. Burger, Peter C. Jouvet, Anne Scheithauer, Bernd W. Kleihues, Paul TI The 2007 WHO classification of tumours of the central nervous system (vol 114, pg 97, 2007) SO ACTA NEUROPATHOLOGICA LA English DT Correction ID ASTROCYTOMAS C1 Univ Zurich Hosp, Dept Pathol, CH-8091 Zurich, Switzerland. Mayo Clin, Dept Lab Med & Pathol, Rochester, MN 55905 USA. Int Agcy Res Canc, F-69008 Lyon, France. German Canc Res Ctr, D-69120 Heidelberg, Germany. Univ Calif San Diego, Ludwig Inst Canc Res, La Jolla, CA 92093 USA. Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21210 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Neurol & Neurosurg Hosp, E Pathol & Neuropathol Ctr, F-69003 Lyon, France. RP Kleihues, P (reprint author), Univ Zurich Hosp, Dept Pathol, CH-8091 Zurich, Switzerland. EM paul.kleihues@usz.ch NR 4 TC 15 Z9 17 U1 4 U2 49 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 2007 VL 114 IS 5 BP 547 EP 547 DI 10.1007/s00401-007-0278-6 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 216YU UT WOS:000249915800012 ER PT J AU Nicholas, PK Voss, JG Corless, IB Lindgren, TG Wantland, DJ Kemppainen, JK Canaval, GE Sefcik, EF Nokes, KM Bain, CA Kirksey, KM Eller, LS Dole, PJ Hamilton, MJ Coleman, CL Holzemer, WL Reynolds, NR Portillo, CJ Bunch, EH Tsai, YF Mendez, MR Davis, SM Gallagher, DM AF Nicholas, P. K. Voss, J. G. Corless, I. B. Lindgren, T. G. Wantland, D. J. Kemppainen, J. K. Canaval, G. E. Sefcik, E. F. Nokes, K. M. Bain, C. A. Kirksey, K. M. Eller, L. S. Dole, P. J. Hamilton, M. J. Coleman, C. L. Holzemer, W. L. Reynolds, N. R. Portillo, C. J. Bunch, E. H. Tsai, Y-F. Mendez, M. R. Davis, S. M. Gallagher, D. M. TI Unhealthy behaviours for self-management of HIV-related peripheral neuropathy SO AIDS CARE-PSYCHOLOGICAL AND SOCIO-MEDICAL ASPECTS OF AIDS/HIV LA English DT Article ID DISTAL SENSORY POLYNEUROPATHY; ANTIRETROVIRAL THERAPY; RISK-FACTORS; AIDS; INFECTION; PAIN; PATHOPHYSIOLOGY; EPIDEMIOLOGY; HISTORY; DISEASE AB The prevalence of peripheral neuropathy is frequent in HIV disease and is often associated with antiretroviral therapy. Unhealthy behaviours, particularly substance-use behaviours, are utilized by many HIV-positive individuals to manage neuropathic symptoms. As part of a larger study on self-care for symptoms in HIV disease, this study analyzed the prevalence and characteristics of unhealthy behaviours to self-manage peripheral neuropathy in HIV disease. Socio-demographic and disease-related correlates and unhealthy behaviours were examined in a convenience sample of 1,217 respondents who were recruited from data collection sites in several US cities, Puerto Rico, Colombia, and Taiwan. Results of the study indicated that respondents with peripheral neuropathy (n = 450) identified a variety of unhealthy self-care behaviours including injection drug use, oral drug use, smoking cigarettes and alcohol ingestion. Specific unhealthy behaviours that participants reported to alleviate peripheral neuropathy included use of marijuana (n = 67), smoking cigarettes (n = 139), drinking alcohol (n = 8 1) and street drugs (n = 30). A subset of those individuals (n = 160), who identified high levels of neuropathy (greater than five on a scale of 1-10), indicated significantly higher use of amphetamines and injection drug use in addition to alcohol use and cigarette smoking. For participants from Norway, substance use (using alcohol: 56%) was one of the most frequent self-management strategies. Implications for clinical practice include assessment and education of persons with HIV for self-care management of the complex symptom of peripheral neuropathy. C1 [Nicholas, P. K.; Corless, I. B.] MGH Inst Hlth Profess, Grad Program Nursing, Boston, MA 02129 USA. [Nicholas, P. K.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Voss, J. G.] Univ Washington, Seattle, WA 98195 USA. [Lindgren, T. G.; Wantland, D. J.; Holzemer, W. L.; Portillo, C. J.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Kemppainen, J. K.] Univ N Carolina, Wilmington, NC 28401 USA. [Canaval, G. E.; Bain, C. A.] Univ Valle, Cali, Colombia. [Sefcik, E. F.] Texas A&M Univ, Corpus Christi, TX USA. [Nokes, K. M.] CUNY Hunter Coll, New York, NY 10021 USA. [Kirksey, K. M.] Ben Taub Gen Hosp, Houston, TX 77030 USA. [Eller, L. S.] Rutgers State Univ, Newark, NJ 07102 USA. [Dole, P. J.] Greenwich House, New York, NY USA. [Coleman, C. L.] Univ Penn, Philadelphia, PA 19104 USA. [Reynolds, N. R.] Ohio State Univ, Columbus, OH 43210 USA. [Bunch, E. H.] Univ Oslo, Oslo, Norway. [Tsai, Y-F.] Chang Gung Univ, Tao Yuan, Taiwan. [Mendez, M. R.] Univ Puerto Rico, San Juan, PR 00936 USA. [Davis, S. M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Gallagher, D. M.] New England AIDS Educ & Training Ctr, Boston, MA USA. RP Nicholas, PK (reprint author), MGH Inst Hlth Profess, Grad Program Nursing, 36 1st Ave, Boston, MA 02129 USA. EM pnicholas@mghihp.edu RI Canaval, Gladys/F-7284-2015; OI Canaval, Gladys/0000-0001-9841-5084; Corless, Inge/0000-0003-0438-2037 NR 41 TC 18 Z9 18 U1 2 U2 3 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0954-0121 J9 AIDS CARE JI Aids Care-Psychol. Socio-Med. Asp. Aids-Hiv PD NOV PY 2007 VL 19 IS 10 BP 1266 EP 1273 DI 10.1080/09540120701408928 PG 8 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychology, Multidisciplinary; Respiratory System; Social Sciences, Biomedical SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychology; Respiratory System; Biomedical Social Sciences GA 254NS UT WOS:000252593900011 PM 18071970 ER PT J AU Antoni, S Walz, N Landersz, M Humbert, M Seidl, C Dittmar, MT Dietrich, U AF Antoni, Sascha Walz, Nicole Landersz, Margot Humbert, Michael Seidl, Christian Dittmar, Matthias T. Dietrich, Ursula TI Genetic and biological characterization of recombinant HIV type 1 with Env derived from long-term nonprogressor (LTNP) viruses SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article; Proceedings Paper CT 16th International AIDS Conference CY AUG 13-18, 2006 CL Toronto, CANADA ID HUMAN-IMMUNODEFICIENCY-VIRUS; FUSION INHIBITOR T-20; PRIMERS PCR-SSP; DISEASE PROGRESSION; REPLICATION-COMPETENT; ELITE SUPPRESSORS; CELL TROPISM; VIRAL LOAD; IN-VIVO; HLA-B AB Multiple factors are known to contribute to nonprogressive disease in long-term nonprogressors (LTNP). We previously selected LTNPs, in which broadly neutralizing antibodies against HIV-1 very likely contribute to disease prevention. Here, we characterize those LTNPs further. We analyzed sequences of the viral genes env, nef, vpr, tat, and rev as well as the cellular ccr5, HLA-B*5701, and HLA-B*27 genes derived from eight LTNPs, as mutations in these genes have been associated with the LTNP status in some studies. Furthermore, we compared the replication rates of recombinant reporter viruses carrying envelope proteins from LTNPs to control viruses from patients with similar CD4 count and viral load. Concerning the cellular factors, none of the eight LTNPs showed the 32-base pair deletion in the ccr5 gene, and HLA-B*5701 and HLA-B*27 alleles were detected in only one LTNP, respectively. The reading frames for the regulatory genes nef, vpr, tat, and rev were all open. Although Env sequences from LTNPs differed from those of control patients with respect to the length of variable domains and the number of N-glycosylation sites, these differences were not statistically significant and did not lead to differences in infectivity of recombinant reporter viruses. C1 Georg Speyer Haus, Biomed Res Inst, D-60596 Frankfurt, Germany. Dana Farber Canc Inst, Boston, MA 02115 USA. Red Cross Blood Donor Serv, Dept Transplantat Immunol & Immunogenet, Frankfurt, Germany. Barts & London Queen Marys Sch Med & Dent, Inst Cell & Mol Sci Barts & London, Ctr Infect Dis, London, England. RP Dietrich, U (reprint author), Georg Speyer Haus, Biomed Res Inst, Paul Ehrlich Str 42-44, D-60596 Frankfurt, Germany. EM ursula.dietrich@em.uni-frankfurt.de NR 60 TC 3 Z9 4 U1 0 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD NOV PY 2007 VL 23 IS 11 BP 1377 EP 1386 DI 10.1089/aid.2007.0113 PG 10 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 239SU UT WOS:000251538800011 PM 18184081 ER PT J AU Durazzo, TC Rothlind, JC Cardenas, VA Studholme, C Weiner, MW Meyerhoff, DJ AF Durazzo, Timothy C. Rothlind, Johannes C. Cardenas, Valerie A. Studholme, Colin Weiner, Michael W. Meyerhoff, Dieter J. TI Chronic cigarette smoking and heavy drinking in human immunodeficiency virus: consequences for neurocognition and brain morphology SO ALCOHOL LA English DT Review DE HIV; alcohol use disorders; chronic cigarette smoking; neuroimaging; neurocognition ID MAGNETIC-RESONANCE SPECTROSCOPY; HIV-INFECTED PATIENTS; CEREBRAL-BLOOD-FLOW; QUALITY-OF-LIFE; ALCOHOL-USE; COGNITIVE PERFORMANCE; NEUROPSYCHOLOGICAL PERFORMANCE; FEMALE ALCOHOLICS; OXIDATIVE DAMAGE; RISK-FACTORS AB Alcohol use disorders (AUD) and chronic cigarette smoking are common among individuals with human immunodeficiency virus infection (HIV). Concurrent AUD in HIV is related to greater abnormalities in brain morphology and neurocognition than either condition alone. However, the potential influence of chronic smoking on brain morphology and neurocognition in those concurrently afflicted with AUD and HIV has not been examined. The goal of this retrospective analysis was to determine if chronic smoking affected neurocognition and brain morphology in a subsample of HIV-positive non-treatment-seeking heavy drinking participants (HD+) from our earlier work. Regional volumetric and neurocognitive comparisons were made among age-equivalent smoking HD+(n = 17), nonsmoking HD+ (n = 27), and nonsmoking HIV-negative light drinking controls (n = 27) obtained from our original larger sample. Comprehensive neuropsychological assessment evaluated multiple neurocognitive domains of functioning and for potential psychiatric comorbidities. Quantitative volumetric measures of neocortical gray matter (GM), white matter (WM), subcortical structures, and sulcal and ventricular cerebral spinal fluid (CSF) were derived from high-resolution magnetic resonance images. The main findings were (1) smoking HD+ performed significantly worse than nonsmoking HD+ on measures of auditory-verbal (AV) learning, AV memory, and cognitive efficiency; (2) relative to controls, smoking HD+ demonstrated significantly lower neocortical GM volumes in all lobes except the occipital lobe, while nonsmoking HD+ showed only lower frontal GM volume compared with controls; (3) in the HD+ group, regional brain volumes and neurocognition were not influenced by viremia, highly active antiretroviral treatment, or Center for Disease Control symptom status, and no interactions were apparent with these variables or smoking status. Overall, the findings suggested that the direct and/or indirect effects of chronic cigarette smoking created an additional burden on the integrity of brain neurobiology and neurocognition in this cohort of HIV-positive heavy drinkers. (c) 2007 Elsevier Inc. All rights reserved. C1 San Francisco Vet Adm Med Ctr, Ctr Imaging Neurodegenerat Dis, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA USA. Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. RP Durazzo, TC (reprint author), San Francisco Vet Adm Med Ctr, Ctr Imaging Neurodegenerat Dis, 114 M, 4150 Clement St, San Francisco, CA 94121 USA. EM timothy.durazzo@ucsf.edu FU NIA NIH HHS [P01 AG019724, P01 AG019724-050002]; NIAAA NIH HHS [L30 AA017007, L30 AA017007-01, P01 AA011493, P01 AA11493, R01 AA010788, R01 AA10788]; NIMH NIH HHS [R01 MH065392, R01 MH65392] NR 115 TC 28 Z9 28 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-8329 J9 ALCOHOL JI Alcohol PD NOV PY 2007 VL 41 IS 7 BP 489 EP 501 DI 10.1016/j.alcohol.2007.07.007 PG 13 WC Substance Abuse; Pharmacology & Pharmacy; Toxicology SC Substance Abuse; Pharmacology & Pharmacy; Toxicology GA 232VD UT WOS:000251047300003 PM 17923369 ER PT J AU Wilhelm, CJ Reeves, JM Phillips, TJ Mitchell, SH AF Wilhelm, Clare J. Reeves, Jamie M. Phillips, Tamara J. Mitchell, Suzanne H. TI Mouse lines selected for alcohol consumption differ on certain measures of impulsivity SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE impulsivity; inhibition; delay discounting; Go/No-Go task; selected mouse lines ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; BEHAVIORAL DISINHIBITION; FAMILY-HISTORY; MICE; ETHANOL; DRINKING; RECEPTORS; LESIONS; CHOICE; TASK AB Background: Alcoholics and heavy drinkers score higher on measures of impulsivity than nonalcoholics and light drinkers. This may be due to factors that predate drug exposure (e.g. genetics) or to neuroadaptations associated with exposure to alcohol. The aim of this study was to examine the role of genetics by comparing impulsivity in short-term selected lines of mice bred to voluntarily drink either high (STDRHI2) or low (STDRLO2) amounts of 10% ethanol. Methods: Independent sets of mice completed 2 experiments designed to measure impulsivity. Using the adjusting amount procedure, we examined preference for smaller, sooner rewards over larger but delayed rewards (delay discounting). This task determines the amount of immediate sucrose equivalent to the discounted value of a 20 mu l sucrose reward given following a specific delay (0, 2, 4, 8, or 12 seconds). Using a Go/No-go task, we examined the ability of mice to inhibit nose-poking in response to specific cues. These tasks are commonly used to assess different aspects of impulsive behavior, and provide measures that are not highly correlated. Results: No significant differences were found between STDRHI2 and STDRLO2 mice in delay discounting. In the Go/No-go task, STDRHI2 mice made more responses during the pre-cue period without committing more false alarms, compared with STDRLO2 mice. Conclusions: The results suggest that short-term selective breeding for high relative alcohol consumption may also select for animals that have impaired response inhibition. C1 Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. Portland VA Med Ctr, Portland, OR USA. Portland VA Med Ctr, Portland, OR USA. RP Wilhelm, CJ (reprint author), Oregon Hlth & Sci Univ, Dept Behav Neurosci, L470,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM wilhelmc@ohsu.edu OI Mitchell, Suzanne/0000-0002-0225-7200 FU NIAAA NIH HHS [AA10760, P60 AA010760, AA007468, AA013518]; NIDA NIH HHS [DA016727] NR 27 TC 33 Z9 33 U1 1 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD NOV PY 2007 VL 31 IS 11 BP 1839 EP 1845 DI 10.1111/j.1530-0277.2007.00508.x PG 7 WC Substance Abuse SC Substance Abuse GA 221TG UT WOS:000250249600009 PM 17850219 ER PT J AU Price, CJ McBride, B Hyerle, L Kivlahan, DR AF Price, Cynthia J. McBride, Brittney Hyerle, Lynne Kivlahan, Daniel R. TI MINDFUL AWARENESS IN BODY-ORIENTED THERAPY FOR FEMALE VETERANS WITH POST-TRAUMATIC STRESS DISORDER TAKING PRESCRIPTION ANALGESICS FOR CHRONIC PAIN: A FEASIBILITY STUDY SO ALTERNATIVE THERAPIES IN HEALTH AND MEDICINE LA English DT Article AB Context Preliminary studies of body therapy for women in trauma recovery suggest positive results but are not specific to women with post-traumatic stress disorder (PTSD) and chronic pain. Objective and Participants To examine the feasibility and acceptability of body-oriented therapy for female veterans with PTSD and chronic pain taking prescription analgesics. Design and Setting: A 2-group, randomized, repeated-measures design was employed. Female veterans (N=14) were recruited from a Veterans Affairs (VA) healthcare system in the Northwest United States (VA Puget Sound Health Care System, Seattle, Washington). Participants were assigned to either treatment as usual (TAU) or treatment as usual and 8 weekly individual body-oriented therapy sessions (mindful awareness in body-oriented therapy group). Measures Written. questionnaires and interviews were used to assess intervention acceptability; reliable and valid measures were administered at 3 time points to evaluate measurement acceptability and performance; and within-treatment process measures and a participant post-intervention questionnaire assessed treatment fidelity. Intervention A body-oriented therapy protocol, "Mindful Awareness in Body-oriented Therapy" (MABT) was used. This is a mind-body approach that incorporates massage, mindfulness, and the emotional processing of psychotherapy. Results Over 10 weeks of recruitment, 31 women expressed interest in study participation. The primary reason for exclusion was the lack of prescription analgesic use for chronic pain. Study participants adhered to study procedures, and 100% attended at least 7 of 8 sessions; all completed in-person post-treatment assessment. Written questionnaires about intervention experience suggest increased tools for pain relief/relaxation, increased body/mind connection, and increased trust/safety. Ten of 14 responded to mailed 3-month follow-up. The response-to-process measures indicated the feasibility of implementing the manualized protocol and point to the need for longer sessions and a longer intervention period with this population. (Altern Ther Health Med. 2007;13(6):32-40.) C1 [Price, Cynthia J.; Kivlahan, Daniel R.] Univ Washington, Seattle, WA 98195 USA. [McBride, Brittney; Hyerle, Lynne] VA Puget Sound Hlth Care Syst, Seattle, WA USA. RP Price, CJ (reprint author), Univ Washington, Seattle, WA 98195 USA. FU University of Washington School of Nursing [T32-DAO7257-15]; Mental Illness Research, Education, and Clinical Center at the VA FX This study was a part of the training and education for the primary author, who was supported by a postdoctoral fellowship on NIDA training grant (#T32-DAO7257-15) offered through the University of Washington School of Nursing, for which she would like to acknowledge the support and mentorship of Daniel Kivlahan, PhD, and Kathryn Bradley, MD, in relationship to this study The authors would like to acknowledge the study participants for their willingness to engage in this study and for sharing their thoughts and experiences with the research team, as well as the funding for study participation that was provided by the Mental Illness Research, Education, and Clinical Center at the VA. NR 42 TC 19 Z9 20 U1 3 U2 10 PU INNOVISION COMMUNICATIONS PI ALISO VIEJO PA 101 COLUMBIA, ALISO VIEJO, CA 92656 USA SN 1078-6791 J9 ALTERN THER HEALTH M JI Altern. Ther. Health Med. PD NOV-DEC PY 2007 VL 13 IS 6 BP 32 EP 40 PG 9 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA V12YO UT WOS:000207634700004 PM 17985809 ER PT J AU Lampe, F Snyder, S Herbert, M AF Lampe, Frank Snyder, Suzanne Herbert, Martha TI MARTHA HERBERT, MD: TRANSCENDING THE GAPS IN AUTISM RESEARCH SO ALTERNATIVE THERAPIES IN HEALTH AND MEDICINE LA English DT Editorial Material C1 [Herbert, Martha] Harvard Univ, Sch Med, Boston, MA USA. [Herbert, Martha] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Herbert, Martha] Harvard MIT MGH Martinos Ctr Biomed Imaging, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU INNOVISION COMMUNICATIONS PI ALISO VIEJO PA 101 COLUMBIA, ALISO VIEJO, CA 92656 USA SN 1078-6791 J9 ALTERN THER HEALTH M JI Altern. Ther. Health Med. PD NOV-DEC PY 2007 VL 13 IS 6 BP 62 EP 73 PG 12 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA V12YO UT WOS:000207634700008 ER PT J AU Morrow, JP Cannon, CP Reiffel, JA AF Morrow, John P. Cannon, Christopher P. Reiffel, James A. TI New antiarrhythmic drugs for establishing sinus rhythm in atrial fibriallation: What are our therapies likely to be by 2010 and beyond? SO AMERICAN HEART JOURNAL LA English DT Article ID STROKE PREVENTION; ROTIGAPTIDE ZP123; RANDOMIZED-TRIAL; FIBRILLATION; DRONEDARONE; AMIODARONE; EFFICACY; AZD7009; AGENT; MODEL AB The management of atrial fibrillation (AF) is plagued by, among other things, limitations in the efficacy, tolerance, and safety of currently available agents for the conversion of AF to sinus rhythm and for the maintenance of sinus rhythm. This review describes some of the most promising approaches to new therapies that may overcome some of the limitations of our current therapies. The agents we have chosen to review are representative of these new approaches and have completed their phase III trials and have submitted an application for approval for release by regulatory agencies or have almost completed their phase III trials and appear likely to submit for approval in the not to distant future. C1 Columbia Univ, Dept Med, Div Cardiol, New York, NY USA. New York Presbyterian Hosp, New York, NY USA. Harvard Univ, Sch Med, Dept Med, Div Cardiovasc,TIMI Study Grp, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Reiffel, JA (reprint author), 161 Ft Washington Ave, New York, NY 10032 USA. EM jar2@columbia.edu OI Morrow, John/0000-0002-9264-5273 NR 36 TC 10 Z9 11 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD NOV PY 2007 VL 154 IS 5 BP 824 EP 829 DI 10.1016/j.ahj.2007.06.041 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 234FT UT WOS:000251146800005 PM 17967585 ER PT J AU Michael, P Fihn, SD Wang, L Bryson, CL Lowy, E Maynard, C Magid, DJ Peterson, ED Jesse, RL Rumsfeld, JS AF Michael, P. Fihn, Stephan D. Wang, Li Bryson, Chris L. Lowy, Elliott Maynard, Charles Magid, David J. Peterson, Eric D. Jesse, Robert L. Rumsfeld, John S. TI Clopidogrel and long-term outcomes after stent implantation for acute coronary syndrome SO AMERICAN HEART JOURNAL LA English DT Article ID DRUG-ELUTING STENTS; ACUTE MYOCARDIAL-INFARCTION; UNCOATED STENTS; THROMBOSIS; THERAPY; TRIAL; INTERVENTION; MEDICATION; PREVALENCE; MORTALITY AB Background Little is known about the association between clopidogrel use and long-term outcomes after stent implantation for acute coronary syndromes (ACS) in clinical practice. Methods This retrospective cohort study included patients with ACS receiving drug-eluting stent (DES) or bare-metal stent (BMS) and discharged from all Veterans Health Administration hospitals from 2003 to 2004. Clopidogrel use was assessed by pharmacy dispensing data. Multivariable Cox regression assessed the association between clopidogrel discontinuation and outcomes with clopidogrel use as a time-varying covariate and adjusting for demographics, comorbidities, hospital presentation, and treatment variables. Median follow-up was 538 days. Results Of 1455 patients with ACS, 65.8% received BMS and 34.2% received DES. The median number of days of clopidogrel use was 299. In multivariable analysis, clopidogrel discontinuation was associated with higher all-cause mortality (hazard ratio [HR] 2.40, 95% confidence interval [Cl] 1.61-3.58). The findings were consistent for patients receiving BMS (HR 2.65, 95% Cl 1.59-4.42) or DES (HR 2.00, 95% Cl 1.06-3.75) and for the outcomes of acute myocardial infarction (AMI) and AMI or mortality. When follow-up was divided into 6-month intervals, the association between clopidogrel discontinuation and higher mortality remained consistent up to 18 months after hospital discharge. In secondary analysis of patients who were event-free at 6 months, clopidogrel discontinuation was associated with higher risk for AMI among patients receiving DES (HR 3.57, 95% Cl 1. 13-11.3) compared with BMS (HR 1.26, 95% Cl 0.58-2.74). Conclusion Clopidogrel discontinuation after extended use was still associated with increased mortality risk. Clinical trials are urgently needed to define the optimal duration of clopidogrel therapy after stent implantation for ACS. C1 Denver VA Med Ctr, Denver, CO 80220 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. Ischem Heart Dis Qual Enhancement Res Initiat, Seattle, WA USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Washington, Seattle, WA 98195 USA. Kaiser Permanente, Clin Res Unit, Aurora, CO USA. Duke Clin Res Inst, Durham, NC USA. Richmond VA Med Ctr, Richmond, VA USA. RP Michael, P (reprint author), Denver VA Med Ctr, 1055 Clermont St,Cardiol 111B, Denver, CO 80220 USA. EM michael.ho@uchsc.edu RI Maynard, Charles/N-3906-2015 OI Maynard, Charles/0000-0002-1644-7814 NR 34 TC 0 Z9 0 U1 1 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 EI 1097-5330 J9 AM HEART J JI Am. Heart J. PD NOV PY 2007 VL 154 IS 5 BP 846 EP 851 DI 10.1016/j.ahj.2007.08.028 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 234FT UT WOS:000251146800008 ER PT J AU O'Donoghue, M Kenney, P Oestreicher, E Anwaruddin, S Baggish, AL Krauser, DG Chen, A Tung, R Cameron, R Januzzi, JL AF O'Donoghue, Michelle Kenney, Patrick Oestreicher, Eveline Anwaruddin, Saif Baggish, Aaron L. Krauser, Daniel G. Chen, Annabel Tung, Roderick Cameron, Renee Januzzi, James L., Jr. TI Usefulness of aminoterminal pro-brain natriuretic peptide testing for the diagnostic and prognostic evaluation of dyspneic patients with diabetes Mellitus seen in the emergency department (from the PRIDE study) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CONGESTIVE-HEART-FAILURE; NT-PROBNP; CARDIOVASCULAR-DISEASE; FRAMINGHAM; EPIDEMIOLOGY; IMPACT; TRIAL AB Despite widespread testing, the utility of aminoterminal pro-brain natriuretic peptide (NT-pro-BNP) for diagnosis or risk assessment in patients with diabetes mellitus (DM) in the emergency department (ED) remains unclear. NT-pro-BNP was measured in subjects with dyspnea. in the ED. A final diagnosis of acute heart failure (HF) was determined by blinded study physicians using all available hospital records. Vital status was assessed at 1 year; independent predictors of death were identified using Cox analysis. Of 599 subjects, 157 (26.2%) had DM, which was an independent predictor of a final diagnosis of acute HF. In patients diagnosed with acute HF, median concentrations of NT-pro-BNP were similar in patients with and without DM (4,784 vs 3,382 pg/ml, respectively, p = 0.93). In dyspneic subjects without acute HF, median concentrations of NT-pro-BNP were significantly higher in patients with DM (242 vs 115 pg/ml, p = 0.01), but this difference was no longer significant after adjusting for relevant covariates. The area under the curve for NT-pro-BNP to diagnose acute HF in subjects with DM was 0.94 (p <0.001). Using age-adjusted cutpoints, NT-pro-BNP was 92% sensitive and 90% specific for the diagnosis of HF in diabetic subjects. In diabetic patients, a NT-pro-BNP level; >= 986 pg/ml was independently associated with an increased risk of death at 1 year (hazard ratio 3.42, 95% confidence interval 1.09 to 10.7, p <0.001). In conclusion, NT-pro-BNP testing offers valuable diagnostic and prognostic information in the evaluation of dyspneic patients with DM in the ED, using identical cutpoints as the population as whole. (c) 2007 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP O'Donoghue, M (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. EM modonoghue@partners.org NR 25 TC 13 Z9 14 U1 0 U2 0 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD NOV 1 PY 2007 VL 100 IS 9 BP 1336 EP 1340 DI 10.1016/j.amjcard.2007.06.020 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 228EO UT WOS:000250710400002 PM 17950786 ER PT J AU Gao, X Chen, HL Fung, TT Logroscino, G Schwarzschild, MA Hu, FB Ascherio, A AF Gao, Xiang Chen, Honglei Fung, Teresa T. Logroscino, Giancarlo Schwarzschild, Michael A. Hu, Frank B. Ascherio, Alberto TI Prospective study of dietary pattern and risk of Parkinson disease SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE Parkinson disease; dietary pattern; prospective study; dietary index; principal components analysis ID CORONARY-HEART-DISEASE; FOOD-FREQUENCY QUESTIONNAIRE; NUTRITION EXAMINATION SURVEY; HEALTHY LIFE-STYLE; URIC-ACID LEVELS; METHYLENETETRAHYDROFOLATE REDUCTASE; NEURODEGENERATIVE DISEASES; ENDOTHELIAL DYSFUNCTION; PLASMA-CONCENTRATIONS; MEDITERRANEAN DIET AB Background: Several studies have shown associations between Parkinson Disease (PD) risk and individual foods and nutrients with inconsistent results. Objective: We examined associations between dietary patterns and risk of PD in the Health Professionals Follow-Up Study (19862002) and the Nurses' Health Study (1984-2000). Design: We included 49 692 men and 81676 women free of PD at baseline and used principal components analysis to identify major dietary patterns and the Alternate Healthy Eating Index (AHEI) and the alternate Mediterranean Diet Score (aMed) to assess diet quality. Relative risks (RRs) were computed by using Cox proportional hazards models within each cohort and were pooled by using a random-effects model. Results: We documented 508 new PD cases after 16 y of follow-up. The principal components analysis identified 2 dietary patterns: prudent and Western. The prudent dietary pattern, characterized by high intakes of fruit, vegetables, and fish, was inversely associated with PD risk. but the Western pattern was not. The pooled multivariate-adjusted RR for the top compared with the bottom quintiles of the prudent score was 0.78 (95% Cl: 0.56. 1.07; P for trend = 0.04). For the AHEI, the pooled multivariate-adjusted RR for the top compared with the bottom quintile was 0.70 (95% Cl: 0.51. 0.94; P for trend 0.01) and for aMED was 0.75 (95% Cl: 0.57. 1.00; P for trend 0.07). Conclusions: Dietary patterns with a high intake of fruit, vegetables, legumes, whole grains, nuts, fish, and poultry and a low intake of saturated fat and a moderate intake of alcohol may protect against PD. Benefits of a plant-based dietary pattern including fish to PD merit further investigation. C1 Harvard Univ, Sch Publ Hlth, Dept Nutr, Cambridge, MA 02138 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Cambridge, MA 02138 USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. Simmons Coll, Dept Nutr, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Gao, X (reprint author), Harvard Univ, Sch Publ Hlth, Dept Nutr, 655 Huntington Ave, Boston, MA 02115 USA. EM xgao@hsph.harvard.edu RI LOGROSCINO, GIANCARLO/K-5148-2016; OI LOGROSCINO, GIANCARLO/0000-0003-0423-3242; Chen, Honglei/0000-0003-3446-7779 FU Intramural NIH HHS [Z01 ES101986-02]; NINDS NIH HHS [R01 NS048517, R01 NS048517-01A2, R01 NS048517-03] NR 49 TC 95 Z9 96 U1 2 U2 13 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD NOV PY 2007 VL 86 IS 5 BP 1486 EP 1494 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 231HE UT WOS:000250936500032 PM 17991663 ER PT J AU Lees, RS AF Lees, Robert S. TI Prevention of atherosclerosis progression in asymptomatic healthy elderly SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article; Proceedings Paper CT Symposium on Keeping the Young-Elderly Healthy CY JUN 06-09, 2005 CL Harvard Coll, Cambridge, MA HO Harvard Coll DE blood lipids; cholesterol-lowering drugs; HDL-raising drugs; antithrombotic drugs; carotid ultrasound; plaque regression ID CORONARY-ARTERIES; DENSITY; DISEASE; WOMEN; PRAVASTATIN; THERAPY AB This review focuses on the role of lipid-lowering, blood pressure-lowering, antithrombotic drugs and diet and their place in the prevention and treatment of atherosclerosis in middle-aged and elderly men and woman. The major emphasis is on noninvasive assessment of the extent of atherosclerotic plaque and the importance of following plaque progression or regression by use of noninvasive ultrasound. With these data, we can demonstrate to both patients and physicians the value, at any age, of treating hypertension and abnormal blood lipids. C1 MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. Harvard Univ, Div Hlth Sci & Technol, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Div Cardiol, Cambridge, MA USA. RP Lees, RS (reprint author), MIT, Div Hlth Sci & Technol, Room E25-519, Cambridge, MA 02139 USA. EM rsl@mit.edu NR 14 TC 2 Z9 2 U1 0 U2 2 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD NOV PY 2007 VL 86 IS 5 BP 1569S EP 1571S PG 3 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 231HE UT WOS:000250936500049 PM 17991677 ER PT J AU Vinson, DR Magid, DJ Brand, DW Masoudi, FA Ho, PM Lyons, EE Crounse, L van der Vlugt, TM Padgett, TG Tricomi, AJ Go, AS Rumsfeld, JS AF Vinson, David R. Magid, David J. Brand, David W. Masoudi, Frederick A. Ho, P. Michael Lyons, Ella E. Crounse, Laurie van der Vlugt, Theresa M. Padgett, Thomas G. Tricomi, Albert J. Go, Alan S. Rumsfeld, John S. TI Patient sex and quality of ED care for patients with myocardial infarction SO AMERICAN JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID ASSOCIATION TASK-FORCE; GENDER-DIFFERENCES; NATIONAL REGISTRY; AMERICAN-COLLEGE; ELDERLY-PATIENTS; UNSTABLE ANGINA; ST-ELEVATION; OF-CARE; AGE; WOMEN AB Objective: The aim of the study was to assess the quality of care between male and female emergency department (ED) patients with acute myocardial infarction (AMI). Methods: A 2-year retrospective cohort study of 2215 patients with AMI presenting immediately to 5 EDs from July 1, 2000, through June 30, 2002 was conducted. Data on patient characteristics, clinical presentation, and ED processes of care were obtained from chart and electrocardiogram reviews. Multivariable regression models were used to assess the independent association between sex and the ED administration of aspirin, beta-blockers, and reperfusion therapy to eligible patients with AMI. Results: There were 849 women and 1366 men in the study. Female patients were older than male patients (74.3 years for women vs 66.8 years for men, P < .001). Among ideal patients, women were less likely than men to receive aspirin (76.3% of women vs 81.3% of men, P < .01), beta-blockers (51.7% of women vs 61.4% of men, P < .01), and reperfusion therapy (64.0% of women vs 72.8% of men, P < .05). However, after adjustment for age, there was no longer a significant relationship between sex and the use of aspirin (odds ratio [OR], 0.99; 95% confidence interval [CI], 0.95-1.03), beta-blockers (OR, 0.94; 95% CI, 0.82-1.04), or reperfusion therapy (OR, 1.01; 95% CI, 0.89-1.09). In models adjusting for additional demographic, clinical, and hospital characteristics, there remained no association between sex and the processes of care. Conclusion: Women with AMI treated in the ED have a lower likelihood of receiving aspirin, beta-blocker, and reperfusion therapy. However, this association appears to be explained by the age difference between men and women with AMI. Although there are no apparent sex disparities in care, ED AMI management remains suboptimal for both sexes. (C) 2007 Elsevier Inc. All rights reserved. C1 [Vinson, David R.; van der Vlugt, Theresa M.; Padgett, Thomas G.] So Calif Permanente Med Grp, Sacramento, CA USA. [Magid, David J.; Brand, David W.; Lyons, Ella E.; Crounse, Laurie] Kaiser Permanente Clin Res Unit, Denver, CO USA. [Magid, David J.] Univ Colorado, Hlth Sci Ctr, Dept Prevent Med & Biometr, Denver, CO 80262 USA. [Magid, David J.] Univ Colorado, Hlth Sci Ctr, Div Emergency Med, Denver, CO USA. [Masoudi, Frederick A.; Ho, P. Michael; Tricomi, Albert J.; Rumsfeld, John S.] Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80262 USA. [Go, Alan S.] Kaiser Permanente No Calif, Div Res, Oakland, CA USA. [Ho, P. Michael; Rumsfeld, John S.] Denver VA Med Ctr, Denver, CO USA. [Masoudi, Frederick A.] Denver Hlth Med Ctr, Dept Med, Denver, CO USA. RP Vinson, DR (reprint author), Kaiser Permanente Med Ctr, Dept Emergency Med, 1600 Eureka Rd, Roseville, CA 95661 USA. OI Vinson, David/0000-0001-6559-1858 FU NIA NIH HHS [K08-AG01011] NR 27 TC 3 Z9 3 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0735-6757 J9 AM J EMERG MED JI Am. J. Emerg. Med. PD NOV PY 2007 VL 25 IS 9 BP 996 EP 1003 DI 10.1016/j.ajem.2007.02.049 PG 8 WC Emergency Medicine SC Emergency Medicine GA 240DS UT WOS:000251568000002 PM 18022492 ER PT J AU Moody-Ayers, S Lindquist, K Sen, S Covinsky, KE AF Moody-Ayers, Sandra Lindquist, Karla Sen, Saunak Covinsky, Kenneth E. TI Childhood social and economic well-being and health in older age SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE activities of daily living; frail elderly; health status; mobility limitation; social class ID SELF-RATED HEALTH; BLACK-WHITE DIFFERENCES; BRITISH WOMENS HEART; SOCIOECONOMIC-STATUS; UNITED-STATES; LIFE-COURSE; ADULT MORTALITY; MEXICAN-AMERICANS; LIVING-CONDITIONS; MENS MORTALITY AB Childhood socioeconomic status (SES) acts over a lifetime to influence adult health outcomes. Whether the impact of childhood SES differs by age or race/ethnicity is unclear. The authors studied 20,566 community-living US adults aged >= 50 years. Parental education was the main predictor. Outcomes evaluated (1998-2002) included self-reported health and functional limitation. The influence of childhood SES on later-life health was also examined in groups stratified by age and race/ethnicity, with adjustment for demographic factors and current SES. Participants' mean age was 67 years; 57% were women. By race/ethnicity, 76% were White, 14% were Black, and 8% were Latino. The relation between low parental education and fair/poor self-rated health declined with advancing age (age 50-64 years: adjusted odds ratio (AOR) = 1.42, 95% confidence interval (Cl): 1.24, 1.63; age >= 80 years: AOR = 1.14, 95% Cl: 0.96, 1.36). The relation between low parental education and fair/poor self-rated health differed across racial/ethnic groups and was significant in White (AOR = 1.33,95%Cl: 1.21,1.47) and Black (AOR = 1.37, 95% Cl: 1.14, 1.64) participants but not Latinos. These findings suggest that childhood SES affects health status through midlife but the effects may abate in late life; its effects also may be weaker in Latinos than in Whites or Blacks. C1 San Francisco VA Med Ctr, San Francisco, CA 94121 USA. Univ Calif San Francisco, Sch Med, Dept Med, Div Geriatr, San Francisco, CA USA. Univ Calif San Francisco, Sch Med, Dept Epidemiol & Biostat, San Francisco, CA USA. RP Moody-Ayers, S (reprint author), San Francisco VA Med Ctr, 4150 Clement St, San Francisco, CA 94121 USA. EM sandra.moody@va.gov; Ken.Covinsky@ucsf.edu FU NIA NIH HHS [1R01AG019827-01, K24 AG029812] NR 53 TC 20 Z9 20 U1 0 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD NOV 1 PY 2007 VL 166 IS 9 BP 1059 EP 1067 DI 10.1093/aje/kwm185 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 223VN UT WOS:000250400700010 PM 17720682 ER PT J AU Borrell, LN Jacobs, DR Williams, DR Pletcher, MJ Houston, TK Kiefe, CI AF Borrell, Luisa N. Jacobs, David R., Jr. Williams, David R. Pletcher, Mark J. Houston, Thomas K. Kiefe, Catarina I. TI Self-reported racial discrimination and substance use in the coronary artery risk development in adults study SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE adaptation; psychological; African Americans; alcohol drinking; amphetamines; cannabis; cocaine; prejudice; smoking ID DETROIT METROPOLITAN-AREA; AFRICAN-AMERICAN WOMEN; BLOOD-PRESSURE; SKIN COLOR; PERCEIVED DISCRIMINATION; HEALTH CONSEQUENCES; MENTAL-HEALTH; YOUNG-ADULTS; DRUG-USE; CARDIA AB The authors investigated whether substance use and self-reported racial discrimination were associated in the Coronary Artery Risk Development in Young Adults (CARDIA) Study. Smoking status, alcohol consumption, and lifetime use of marijuana, amphetamines, and opiates were ascertained in 2000-2001, 15 years after baseline (1985-1986). Most of the 1,507 African Americans reported having experienced racial discrimination, 79.5% at year 7 and 74.6% at year 15, compared with 29.7% and 23.7% among the 1,813 Whites. Compared with African Americans experiencing no discrimination, African Americans reporting any discrimination had more education and income, while the opposite was true for Whites (all p < 0.001). African Americans experiencing racial discrimination in at least three of seven domains in both years had 1.87 (95% confidence interval (Cl): 1.18, 2.96) and 2.12 (95% Cl: 1.42, 3.17) higher odds of reporting current tobacco use and having any alcohol in the past year than did their counterparts experiencing no discrimination. With control for income and education, African Americans reporting discrimination in three or more domains in both years had 3.31 (95% Cl: 1.90, 5.74) higher odds of using marijuana 100 or more times in their lifetime, relative to African Americans reporting no discrimination. These associations were similarly positive in Whites but not significant. Substance use may be an unhealthy coping response to perceived unfair treatment for some individuals, regardless of their race/ethnicity. C1 Columbia Univ, Mailman Sch Public Hlth, Dept Epidemiol, New York, NY 10027 USA. Univ Minnesota, Sch Publ Hlth, Div Epidemiol, Minneapolis, MN USA. Univ Oslo, Dept Nutr, Oslo, Norway. Harvard Univ, Sch Publ Hlth, Dept African & American Studies Sociol, Boston, MA USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA USA. Birmingham Vet Affairs Med Ctr, Deep S ctr Effectiveness, Birmingham, AL USA. Univ Alabama, Div Gen Internal Med, Birmingham, AL USA. Univ Alabama, Div Prevent Med, Birmingham, AL USA. RP Borrell, LN (reprint author), Columbia Univ, Mailman Sch Public Hlth, Dept Epidemiol, New York, NY 10027 USA. EM Inb2@columbia.edu RI Houston, Thomas/F-2469-2013 FU NHLBI NIH HHS [N01-HC-48047, N01-HC-48048, N01-HC-48049, N01-HC-48050, N01-HC-95095]; NIDCR NIH HHS [K22-DE-15317] NR 47 TC 123 Z9 123 U1 4 U2 14 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 1 PY 2007 VL 166 IS 9 BP 1068 EP 1079 DI 10.1093/aje/kwm180 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 223VN UT WOS:000250400700011 PM 17698506 ER PT J AU Mintzer, JE Tune, LE Breder, CD Swanink, R Marcus, RN McQuade, RD Forbes, A AF Mintzer, Jacobo E. Tune, Larry E. Breder, Christopher D. Swanink, Rene Marcus, Ronald N. McQuade, Robert D. Forbes, Andy TI Aripiprazole for the treatment of psychoses in institutionalized patients with Alzheimer dementia: A multicenter, randomized, double-blind, placebo-controlled assessment of three fixed doses SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article; Proceedings Paper CT 17th Congress of the European-College-of-Neuropsychopharmacology (ECNP) CY OCT 09-13, 2004 CL Stockholm, SWEDEN SP European Coll Neuropsychopharmacol DE psychosis; Alzheimer dementia; atypical; antipsychotic; aripiprazole ID MANSFIELD AGITATION INVENTORY; CEREBROVASCULAR EVENTS; NEUROPSYCHIATRIC INVENTORY; BEHAVIORAL DISTURBANCES; CONTROLLED TRIALS; PARTIAL AGONIST; NURSING-HOME; DISEASE; RISPERIDONE; RISK AB Objective: To assess the efficacy and safety of aripiprazole for psychosis associated with Alzheimer dementia (AD). Methods: In this double-blind, multicenter study, 487 institutionalized patients with psychosis associated with AD were randomized to placebo or aripiprazole, 2, 5 or 10 mg/day. Primary efficacy assessment was the mean change from baseline to week 10 on the Neuropsychiatric Inventory-Nursing Home ( NPI-NH) version Psychosis Subscale score. Secondary measures included NPI-NH Total, Clinical Global Impression-Severity of Illness ( CGI-S), Brief Psychiatric Rating Scale ( BPRS) Core and Total, and the Cohen-Mansfield Agitation Inventory ( CMAI) scores. Results: Aripiprazole 10 mg/day showed significantly greater improvements ( mean change [2 x SD]) than placebo on the NPI-NH Psychosis Subscale (-6.87 [8.6] versus -5.13 [10.0]; F = 6.29, df = 1, 422, p = 0.013 by analysis of covariance [ANCOVA]); CGI-S (-0.72 [1.8] versus -0.46 [1.6]; F = 4.68, df = 1, 419, p = 0.031 [ANCOVA]); BPRS Total (-7.12 [18.4] versus -4.17 [21.6]; F = 4.72, df = 1, 399, p = 0.030 [ANCOVA]); BPRS Core (-3.07 [6.9] versus -1.74 [7.8]; F = 7.30, df = 1, 407, p = 0.007 [ANCOVA]); CMAI (-10.96 [22.6] versus -6.64 [28.6]; F = 5.23, df = 1, 410, p = 0.023 [ANCOVA]), and NPI-NH Psychosis response rate ( 65 versus 50%; chi(2) = 5.52, df = 1, p = 0.019 [CMH]). Aripiprazole 5 mg/day showed significant improvements versus placebo on BPRS and CMAI scores. Aripiprazole 2 mg/day was not efficacious. Cerebrovascular adverse events were reported: aripiprazole 2 mg/day, N = 1; 5 mg/day, N = 2; 10 mg/day, N = 4; placebo, N = 0. No deaths in any group ( aripiprazole 2 mg/day, 3%; 5 mg/day, 2%; 10 mg/day, 7%; placebo, 3%) were considered to be treatment-related. Conclusion: Aripiprazole 10 mg/day was efficacious and safe for psychosis associated with AD, significantly improving psychotic symptoms, agitation, and clinical global impression. However, clinicians should be aware of the safety considerations of atypical antipsychotic uses in this population. C1 Med Univ S Carolina, Alzheimers Res & Clin Programs, N Charleston, SC 29406 USA. Ralph H Johnson VA Med Ctr, Charleston, SC USA. Emory Univ, Dept Psychiat, Atlanta, GA 30322 USA. Bristol Myers Squibb Co, Wallingford, CT 06492 USA. Bristol Myers Squibb Co, Braine Lalleud, Belgium. Otsuka Pharmaceut Dev & Commercializat, Princeton, NJ USA. Bristol Myers Squibb Co, Princeton, NJ USA. RP Mintzer, JE (reprint author), Med Univ S Carolina, Alzheimers Res & Clin Programs, 5900 Core Rd,Suite 203, N Charleston, SC 29406 USA. EM mintzerj@musc.edu NR 39 TC 52 Z9 52 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1064-7481 J9 AM J GERIAT PSYCHIAT JI Am. J. Geriatr. Psychiatr. PD NOV PY 2007 VL 15 IS 11 BP 918 EP 931 DI 10.1097/JGP.0b013e3181557b47 PG 14 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 226VY UT WOS:000250617800002 PM 17974864 ER PT J AU Venugopal, B Browning, MF Curcio-Morelli, C Varro, A Michaud, N Nanthakumar, N Walkley, SU Pickel, J Slaugenhaupt, SA AF Venugopal, Bhuvarahamurthy Browning, Marsha F. Curcio-Morelli, Cyntia Varro, Andrea Michaud, Norman Nanthakumar, Nanda Walkley, Steven U. Pickel, James Slaugenhaupt, Susan A. TI Neurologic, gastric, and opthalmologic Pathologies in a murine model of Mucolipidosis type IV SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID TARGETED DISRUPTION; LYSOSOMAL STORAGE; CATION CHANNEL; CULTURED FIBROBLASTS; ABNORMAL TRANSPORT; MEMBRANE-PROTEIN; ACID-SECRETION; MOUSE MODEL; GENE; DISEASE AB Mucolipidosis type IV (MLIV) is an autosomal recessive lysosomal storage disorder caused by mutations in the MCOLN1 gene, which encodes the 65-kDa protein mucolipin-1. The most common clinical features of patients with MLIV include severe mental retardation, delayed motor milestones, ophthalmologic abnormalities, constitutive achlorhydria, and elevated plasma gastrin levels. Here, we describe the first murine model for MLIV, which accurately replicates the phenotype of patients with MLIV. The Mcoln1(-/-) mice present with numerous dense inclusion bodies in all cell types in brain and particularly in neurons, elevated plasma gastrin, vacuolization in parietal cells, and retinal degeneration. Neurobehavioral assessments, including analysis of gait and clasping, confirm the presence of a neurological defect. Gait deficits progress to complete hind-limb paralysis and death at age similar to 8 mo. The Mcoln1(-/-) mice are born in Mendelian ratios, and both male and female Mcoln1(-/-) mice are fertile and can breed to produce progeny. The creation of the first murine model for human MLIV provides an excellent system for elucidating disease pathogenesis. In addition, this model provides an invaluable resource for testing treatment strategies and potential therapies aimed at preventing or ameliorating the abnormal lysosomal storage in this devastating neurological disorder. C1 Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dev Gastroenterol Lab, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. Univ Liverpool, Sch Biomed Sci, Physiol Labs, Liverpool L69 3BX, Merseyside, England. Albert Einstein Coll Med, Rose F Kennedy Ctr, Dominck P Purpura Dept Neurosci, Bronx, NY 10467 USA. Natl Inst Mental Hlth Transgen Core, NIH, Bethesda, MD USA. RP Slaugenhaupt, SA (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, 185 Cambridge St, Boston, MA 02114 USA. EM susan_slaugenhaupt@chgr.mgh.harvard.edu RI Varro, Andras/M-2647-2016 OI Varro, Andras/0000-0003-0745-3603 FU NICHD NIH HHS [HD045561, R01 HD045561]; NIDDK NIH HHS [DK12437, DK40561, DK43351, DK57521, DK70260, P30 DK040561, P30 DK043351, P30 DK057521, R01 DK070260]; NIGMS NIH HHS [T32-GM077481-25]; NINDS NIH HHS [1F32NS052072-01A1, F32 NS052072, NS39995, R01 NS039995] NR 73 TC 56 Z9 57 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD NOV PY 2007 VL 81 IS 5 BP 1070 EP 1083 DI 10.1086/521954 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA 224XE UT WOS:000250480900017 PM 17924347 ER PT J AU Setty, AR Curhan, G Choi, HK AF Setty, Arathi R. Curhan, Gary Choi, Hyon K. TI Smoking and the risk of psoriasis in women: Nurses' health study II SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE cessation; cigarette; cohort; pack; years; passive; prospective; psoriasis; risk factors; smoking ID QUALITY-OF-LIFE; CIGARETTE SMOKERS; PROSPECTIVE COHORT; TOBACCO-SMOKE; BIRTH-WEIGHT; POPULATION; OBESITY; INFLAMMATION; ASSOCIATION; PREVALENCE AB Psoriasis is a common, chronic, inflammatory skin disorder. Smoking may increase the risk of psoriasis, but no prospective data are available on this relation. METHODS: We prospectively examined over a 14-year time period (1991-2005) the relation between smoking status, duration, intensity, cessation, and exposure to secondhand smoke, and incident psoriasis in 78,532 women from the Nurses Health Study II. The primary outcome was incident, self-reported, physician-diagnosed psoriasis. RESULTS: We documented 887 incident cases of psoriasis. Compared with those who had never smoked, the multivariate relative risk (RR) of psoriasis was 1.78 (95% confidence interval [CI], 1.46 to 2.16) for current smokers and 1.37 (95% CI, 1.17 to 1.59) for past smokers. Compared with nonsmokers, the multivariate RR of psoriasis was 1.60 (95% CI, 1.31 to 1.97) for those who had smoked 11- 20 pack-years and 2.05 (95% CI, 1.66 to 2.53) for those who had smoked >= 21 pack- years. Compared with never smokers, the multivariate RR of psoriasis was 1.61 ( 95% CI, 1.30 to 2.00) for those who quit smoking < 10 years ago, 1.31 ( 95% CI, 1.05 to 1.64) for 10-19 years ago, and 1.15 ( 95% CI, 0.88 to 1.51) for < 20 years ago. Prenatal and childhood exposure to passive smoke was associated with an increased risk of psoriasis. CONCLUSIONS: In this prospective analysis, current and past smoking, and cumulative measures of smoking were associated with the incidence of psoriasis. The risk of incident psoriasis among former smokers decreases nearly to that of never smokers 20 years after cessation. (C) 2007 Elsevier Inc. All rights reserved. C1 Univ British Columbia, Dept Med, Div Rheumatol, Arthritis Res Ctr, Vancouver, BC V5Z 1L7, Canada. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Rheumatol Allergy & Immunol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Renal Div, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Univ British Columbia, Vancouver Gen Hosp, Dept Med, Arthritis Res Ctr,Rheumatol, Vancouver, BC V5Z 1M9, Canada. RP Choi, HK (reprint author), Univ British Columbia, Dept Med, Div Rheumatol, Arthritis Res Ctr, 895 w 10th Ave, Vancouver, BC V5Z 1L7, Canada. EM hchoi@partners.org FU NCI NIH HHS [R01 CA050385-20, CA50385, R01 CA050385]; NIAMS NIH HHS [T32 AR007258, T32 AR007258-29, 5 T32 AR007258-29] NR 40 TC 92 Z9 93 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD NOV PY 2007 VL 120 IS 11 BP 953 EP 959 DI 10.1016/j.amjmed.2007.06.020 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 226GO UT WOS:000250576100011 PM 17976422 ER PT J AU Ruff, CT Wiviott, SD Morrow, DA Mohanavelu, S Murphy, SA Antman, EM Braunwald, E AF Ruff, Christian T. Wiviott, Stephen D. Morrow, David A. Mohanavelu, Satishkumar Murphy, Sabina A. Antman, Elliott M. Braunwald, Eugene CA ExTRACT-TIMI 25 Invest TI TIMI risk index and the benefit of enoxaparin in patients with ST-elevation myocardial infarction SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE Enoxaparin; fibrinolysis; myocardial infarction; prognosis; TIMI risk index ID ACUTE CORONARY SYNDROMES; UNFRACTIONATED HEPARIN; NATIONAL REGISTRY; STRATIFICATION; THROMBOLYSIS; MORTALITY; SCORE; FIBRINOLYSIS; REPERFUSION; TRIAL AB PURPOSE: The purpose of the study was to evaluate the cause of death, risk of nonfatal complications, and relative outcomes with an enoxaparin versus unfractionated heparin strategy in ST-elevation myocardial infarction stratified using the Thrombolysis in Myocardial Infarction (TIMI) Risk Index (TRI). METHODS: We evaluated 30-day outcomes in 19,941 patients with ST-elevation myocardial infarction treated with fibrinolysis and unfractionated heparin or enoxaparin. Patients were categorized on the basis of prespecified ranges of the TRI [heart rate X(age/10)(2)/systolic blood pressure]. RESULT: There was a strongly graded increase in 30-day mortality with increasing TRI (1.2%-20.7%, P <. 0001). The proportion of deaths due to mechanical causes (congestive heart failure, shock, and myocardial rupture) increased progressively with the TRI. There also was a significant positively graded association between the TRI and nonfatal heart failure or shock (0.4%-4.4%, P <. 0001). In contrast, death resulting from recurrent ischemic events predominated in the lowest TRI group. The relative reduction in death/myocardial infarction with the enoxaparin strategy appeared inversely graded with the TRI. There was a 38% reduction in the lowest risk group (relative risk 0.62, 95% confidence interval 0.45-0.86) and a decrease in the relative benefit of enoxaparin with increasing risk index. CONCLUSIONS: The TRI was a strong predictor of all- cause mortality in a broad population, with a positive association with the risk of death due to mechanical complications and an inverse association with deaths due to recurrent ischemia. The enoxaparin strategy was superior to unfractionated heparin in a majority of patients with ST-elevation myocardial infarction, except for the group at the highest risk for severe mechanical complications, in whom the 2 anticoagulant strategies showed similar results. (C) 2007 Elsevier Inc. All rights reserved. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Cardiovasc Div,TIMI Study Grp, Boston, MA 02115 USA. RP Ruff, CT (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Cardiovasc Div,TIMI Study Grp, 75 Francis St, Boston, MA 02115 USA. EM cruff@partners.org NR 16 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 0002-9343 J9 AM J MED JI Am. J. Med. PD NOV PY 2007 VL 120 IS 11 BP 993 EP 998 DI 10.1016/j.amjmed.2007.08.020 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 226GO UT WOS:000250576100017 PM 17976428 ER PT J AU Park, DY Sakamoto, H Kirley, SD Ogino, S Kawasaki, T Kwon, E Mino-Kenudson, M Lauwers, GY Chung, DC Rueda, BR Zukerberg, LR AF Park, Do Youn Sakamoto, Hideo Kirley, Sandra D. Ogino, Shuji Kawasaki, Takako Kwon, Eunjeong Mino-Kenudson, Mari Lauwers, Gregory Y. Chung, Daniel C. Rueda, Bo R. Zukerberg, Lawrence R. TI The cables gene on chromosome 18q is silenced by promoter hype rmethyl ati on and allelic loss in human colorectal cancer SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID TUMOR-SUPPRESSOR GENE; COLON-CANCER; IN-VIVO; SOMATIC ALTERATIONS; DCC GENE; METHYLATION; PROTEIN; HYPERMETHYLATION; PHOSPHORYLATION; TUMORIGENESIS AB Cables is a cyclin-dependent kinase-binding nuclear protein that maps to chromosome 18q11-12. Here, we assessed Cables expression in 160 colorectal cancers (CRCs), its role in colon cancer cell growth, and the potential mechanisms of Cables inactivation. Expression levels, promoter methylation, and mutational status of Cables were investigated in colon cancer cell lines and primary colon tumors. Chromosome 18q loss of heterozygosity (LOH) was evaluated with multiple polymorphic markers. Cables inhibited cellular proliferation and colony formation in colon cancer cell lines. Cables expression was reduced in 65% of primary CRCs. No mutations were detected in 10 exons; of Cables in 20 primary colon tumors. Cables promoter was methylated in cell lines with decreased Cables expression and vice versa. 5-Aza-2'-deoxycytidine resulted in increased Cables expression in methylated cell lines. There was a significant correlation between promoter methylation and Cables gene expression in primary colon tumors. Sixty-five percent of primary colon tumors demonstrated chromosome 18q LOH. LOH involving the Cables region was observed in 35% of cases, including those in which more distal portions of chromosome 18q were retained, and Cables expression was decreased in all such cases. Loss of Cables expression in 65% of CRCs suggests that it is a common event in colonic carcinogenesis, with promoter methylation and LOH appearing to be important mechanisms of Cables gene inactivation. C1 Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Pusan Natl Univ, Pusan Natl Univ Hosp, Pusan, South Korea. Pusan Natl Univ, Med Res Inst, Pusan, South Korea. RP Zukerberg, LR (reprint author), Massachusetts Gen Hosp, Dept Pathol, Warren 2,55 Fruit St, Boston, MA 02114 USA. EM lzukerberg@partners.org FU NCI NIH HHS [R01 CA 98333, R01 CA098333, R01 CA 103883-01, R01 CA103883] NR 37 TC 13 Z9 13 U1 0 U2 2 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD NOV PY 2007 VL 171 IS 5 BP 1509 EP 1519 DI 10.2353/ajpath.2007.070331 PG 11 WC Pathology SC Pathology GA 228NH UT WOS:000250736100010 PM 17982127 ER PT J AU Bowles, AO Kevorkian, CG Rintala, DH AF Bowles, Amy O. Kevorkian, C. George Rintala, Diana H. TI Gender differences regarding career issues and promotion in academic physical medicine and rehabilitation SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Article DE gender; tenure; attitude; rehabilitation ID WOMEN PHYSICIANS; FACULTY; RECOGNITION; SUCCESS; FEMALE AB Objective: To assess gender differences in academic progress and attitudes toward promotion in academic physical medicine and rehabilitation (PM&R). Design: A survey was sent to members of the Association of Academic Physiatrists (AAP). Questions addressed demographics, job description, hours worked, childcare responsibilities, publications, career aspirations, mentoring, and familiarity with promotion and tenure policies. Respondents were also asked about the relative importance of career aspects including the perceived benefits of and obstacles to promotion. Responses were anonymous. Results: Women spent less time on scholarly activities. Women considered the fact that they disliked writing and did not know how to do research to be more important obstacles to promotion than did men. Women were more likely to have part-time appointments and lower academic rank. They had fewer children at home but greater responsibility for child care. Women were less likely to aspire to become full professor, they met less often with their department chair/supervisor, and they published fewer papers. Men and women reported equal career satisfaction. Conclusions: There are several gender differences in the values, attitudes, and priorities in academic PM&R. Women respondents were generally less interested in traditional academic pursuits than were their male counterparts. C1 Univ Texas, Hlth Sci Ctr, Dept Rehabil Med, San Antonio, TX 78229 USA. Baylor Coll Med, Houston, TX 77030 USA. Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. RP Bowles, AO (reprint author), Univ Texas, Hlth Sci Ctr, Dept Rehabil Med, Mail Code 7798,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. NR 20 TC 13 Z9 13 U1 1 U2 6 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 2007 VL 86 IS 11 BP 918 EP 925 DI 10.1097/PHM.0b013e31815205f7 PG 8 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 226UQ UT WOS:000250614400008 PM 18049138 ER PT J AU Hull, RL Zraika, S Udayasankar, J Kisilevsky, R Szarek, WA Wight, TN Kahn, SE AF Hull, Rebecca L. Zraika, Sakeneh Udayasankar, Jayalakshmi Kisilevsky, Robert Szarek, Walter A. Wight, Thomas N. Kahn, Steven E. TI Inhibition of glycosaminoglycan synthesis and protein glycosylation with WAS-406 and azaserine result in reduced islet amyloid formation in vitro SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE islet amyloid polypeptide; heparan sulfate; proteoglycan; beta-cell mass; beta-cell dysfunction ID FIBRIL FORMATION; APOLIPOPROTEIN-E; HEPARAN-SULFATE; TRANSGENIC MICE; HEXOSAMINE PATHWAY; ALZHEIMERS-DISEASE; DIABETES-MELLITUS; POLYPEPTIDE; BETA; CELLS AB Deposition of islet amyloid polypeptide ( IAPP) as amyloid in the pancreatic islet occurs in similar to 90% of individuals with Type 2 diabetes and is associated with decreased islet beta-cell mass and function. Human IAPP (hIAPP), but not rodent IAPP, is amyloidogenic and toxic to islet beta-cells. In addition to IAPP, islet amyloid deposits contain other components, including heparan sulfate proteoglycans (HSPGs). The small molecule 2-acetamido-1,3,6-tri-O-acetyl-2,4-dideoxy-alpha-D-xylo-hexopyranose (WAS-406) inhibits HSPG synthesis in hepatocytes and blocks systemic amyloid A deposition in vivo. To determine whether WAS-406 inhibits localized amyloid formation in the islet, we incubated hIAPP transgenic mouse islets for up to 7 days in 16.7 mM glucose ( conditions that result in amyloid deposition) plus increasing concentrations of the inhibitor. WAS-406 at doses of 0, 10, 100, and 1,000 mu M resulted in a dose-dependent decrease in amyloid deposition (% islet area occupied by amyloid: 0.66 +/- 0.14%, 0.10 +/- 0.06%, 0.09 +/- 0.07%, and 0.004 +/- 0.003%, P < 0.001) and an increase in beta-cell area in hIAPP transgenic islets (55.0 +/- 2.6 vs. 60.6 +/- 2.2% islet area for 0 vs. 100 mu M inhibitor, P = 0.05). Glycosaminoglycan, including heparan sulfate, synthesis was inhibited in both hIAPP transgenic and nontransgenic islets ( the latter is a control that does not develop amyloid), while O-linked protein glycosylation was also decreased, and WAS-406 treatment tended to decrease islet viability in nontransgenic islets. Azaserine, an inhibitor of the rate-limiting step of the hexosamine biosynthesis pathway, replicated the effects of WAS-406, resulting in reduction of O-linked protein glycosylation and glycosaminoglycan synthesis and inhibition of islet amyloid formation. In summary, interventions that decrease both glycosaminoglycan synthesis and O-linked protein glycosylation are effective in reducing islet amyloid formation, but their utility as pharmacological agents may be limited due to adverse effects on the islet. C1 Vet Affairs Puget Sound Hlth Care Syst, Div Metab Endocrinol & Nutr, Seattle, WA USA. Univ Washington, Dept Pathol, Seattle, WA 98195 USA. Queens Univ, Dept Pathol & Mol Med, Kingston, ON, Canada. Queens Univ, Dept Biochem, Kingston, ON K7L 3N6, Canada. Queens Univ, Dept Chem, Kingston, ON K7L 3N6, Canada. Univ Washington, Benaroya Res Inst Virginia Mason, Hope Heart Program, Seattle, WA 98195 USA. RP Hull, RL (reprint author), VA Puget Sound Hlth Care Syst 151, 1660 S Columbian Way, Seattle, WA 98108 USA. EM rhull@u.washington.edu OI Kahn, Steven/0000-0001-7307-9002 FU NCRR NIH HHS [K23 RR016066, RR-16066]; NIDDK NIH HHS [K01 DK074404-02, DK-74404, K01 DK074404, P30 DK017047] NR 38 TC 29 Z9 31 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD NOV PY 2007 VL 293 IS 5 BP C1586 EP C1593 DI 10.1152/ajpcell.00208.2007 PG 8 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 228EF UT WOS:000250709500018 PM 17804609 ER PT J AU Burns, AR Zheng, Z Soubra, SH Chen, J Rumbaut, RE AF Burns, Alan R. Zheng, Zhilan Soubra, Said H. Chen, Jie Rumbaut, Rolando E. TI Transendothelial flow inhibits neutrophil transmigration through a nitric oxide-dependent mechanism: potential role for cleft shear stress SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE endothelium; neutrophils; hydraulic conductivity; diapedesis; permeability ID SYNTHASE-DEFICIENT MICE; NECROSIS-FACTOR-ALPHA; HYDRAULIC CONDUCTIVITY; ENDOTHELIAL-CELLS; TIGHT JUNCTIONS; INDUCED INCREASE; L-NAME; MIGRATION; MONOLAYERS; ADHESION AB Transendothelial flow inhibits neutrophil transmigration through a nitric oxide-dependent mechanism: potential role for cleft shear stress. Am J Physiol Heart Circ Physiol 293: H2904-H2910, 2007. First published August 24, 2007; doi:10.1152/ajpheart.00871.2007. - Endothelial cells in vivo are well known to respond to parallel shear stress induced by luminal blood flow. In addition, fluid filtration across endothelium (transendothelial flow) may trigger nitric oxide ( NO) production, presumably via shear stress within intercellular clefts. Since NO regulates neutrophil-endothelial interactions, we determined whether transendothelial flow regulates neutrophil transmigration. Interleukin1 beta-treated human umbilical vein endothelial cell ( HUVEC) monolayers cultured on a polycarbonate filter were placed in a custom chamber with or without a modest hydrostatic pressure gradient (Delta P, 10 cmH(2)O) to induce transendothelial flow. In other experiments, cells were studied in a parallel plate flow chamber at various transendothelial flows (Delta P = 0, 5, and 10 cmH(2)O) and luminal flows ( shear stress of 0, 1, and 2 dyn/cm(2)). In the absence of luminal flow, transendothelial flow reduced transmigration of freshly isolated human neutrophils from 57% to 14% ( P < 0.05) and induced an increase in NO detected with a fluorescent assay (DAF-2DA). The NO synthase inhibitor L-NAME prevented the effects of transendothelial flow on neutrophil transmigration, while a NO donor (DETA/NO, 1 mM) inhibited neutrophil transmigration. Finally, in the presence of luminal flow ( 1 and 2 dyn/cm(2)), transendothelial flow also inhibited transmigration. On the basis of HUVEC morphometry and measured transendothelial volume flow, we estimated cleft shear stress to range from 49 to 198 dyn/cm(2). These shear stress estimates, while substantial, are of similar magnitude to those reported by others with similar analyses. These data are consistent with the hypothesis that endothelial cleft shear stress inhibits neutrophil transmigration via a NO-dependent mechanism. C1 Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. Baylor Coll Med, Dept Anesthesiol, Houston, TX 77030 USA. Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. RP Rumbaut, RE (reprint author), Baylor Coll Med, Dept Med, CNRC Bldg,Rm 6014,1100 Bates St, Houston, TX 77030 USA. EM rrumbaut@bcm.tmc.edu FU NHLBI NIH HHS [HL-079368, R01 HL079368, R01 HL079368-01A1, HL-070537, HL-42550]; NIAID NIH HHS [AI-46773] NR 31 TC 9 Z9 9 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD NOV PY 2007 VL 293 IS 5 BP H2904 EP H2910 DI 10.1152/ajpheart.00871.2007 PG 7 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 237TU UT WOS:000251400100034 PM 17720767 ER PT J AU Liu, R Hotta, Y Graveline, AR Evgenov, OV Buys, ES Bloch, KD Ichinose, F Zapol, WM AF Liu, Rong Hotta, Yukako Graveline, Amanda R. Evgenov, Oleg V. Buys, Emmanuel S. Bloch, Kenneth D. Ichinose, Fumito Zapol, Warren M. TI Congenital NOS2 deficiency prevents impairment of hypoxic pulmonary vasoconstriction in murine ventilator-induced lung injury SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE mechanical ventilation; nitric oxide synthase; hypoxia ID RESPIRATORY-DISTRESS-SYNDROME; TIDAL VOLUME VENTILATION; NITRIC-OXIDE SYNTHASE; MECHANICAL VENTILATION; PHOSPHOLIPASE A(2); STRESS FAILURE; IN-VIVO; MICE; CELLS; OXYGENATION AB Hypoxic pulmonary vasoconstriction (HPV) preserves systemic arterial oxygenation during lung injury by diverting blood flow away from poorly ventilated lung regions. Ventilator-induced lung injury (VILI) is characterized by pulmonary inflammation, lung edema, and impaired HPV leading to systemic hypoxemia. Studying mice congenitally deficient in inducible nitric oxide synthase (NOS2) and wild-type mice treated with a selective NOS2 inhibitor, L-N-6-(1-iminoethyl) lysine (L-NIL), we investigated the contribution of NOS2 to the impairment of HPV in anesthetized mice subjected to 6 h of either high tidal volume (HVT) or low tidal volume (LVT) ventilation. HPV was estimated by measuring the changes of left lung pulmonary vascular resistance (LPVR) in response to left mainstem bronchus occlusion (LMBO). LMBO increased the LPVR similarly in wild-type, NOS2(-/-), and wild-type mice treated with L-NIL 30 min before commencing 6 h of LVT ventilation ( 96% +/- 30%, 103% +/- 33%, and 80% +/- 16%, respectively, means +/- SD). HPV was impaired in wild-type mice subjected to 6 h of HVT ventilation (23% +/- 16%). In contrast, HPV was preserved after 6 h of HVT ventilation in NOS2(-/-) and wild-type mice treated with L-NIL either 30 min before or 6 h after commencing HVT ventilation (66% +/- 22%, 82% +/- 29%, and 85% +/- 16%, respectively). After 6 h of HVT ventilation and LMBO, systemic arterial oxygen tension was higher in NOS2(-/-) than in wild-type mice ( 192 +/- 11 vs. 171 +/- 17 mmHg; P < 0.05). We conclude that either congenital NOS2 deficiency or selective inhibition of NOS2 protects mice from the impairment of HPV occurring after 6 h of HVT ventilation. C1 Harvard Univ, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Cardiovasc Res Ctr, Dept Med, Boston, MA 02114 USA. RP Zapol, WM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Fruit St,Clin 309, Boston, MA 02114 USA. EM wzapol@partners.org FU NHLBI NIH HHS [HL-74352, HL-42397, HL-71987] NR 38 TC 6 Z9 7 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD NOV PY 2007 VL 293 IS 5 BP L1300 EP L1305 DI 10.1152/ajplung.00396.2006 PG 6 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 230IR UT WOS:000250870700023 PM 17720871 ER PT J AU Fink, BD Herlein, JA Almind, K Cinti, S Kahn, CR Sivitz, WI AF Fink, Brian D. Herlein, Judy A. Almind, Katrine Cinti, Saverio Kahn, C. Ronald Sivitz, William I. TI Mitochondrial proton leak in obesity-resistant and obesity-prone mice SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE uncoupling protein; mitochondria; obesity ID DIET-INDUCED OBESITY; BROWN ADIPOSE-TISSUE; RAT SKELETAL-MUSCLE; UNCOUPLING PROTEINS; MESSENGER-RNA; INSULIN-RESISTANCE; YEAST MITOCHONDRIA; C57BL/6J MICE; EXPRESSION; LEPTIN AB We quantified uncoupling proteins (UCPs) in molar amounts and assessed proton conductance in mitochondria isolated from interscapular brown adipose tissue ( IBAT) and hindlimb muscle [ known from prior work to contain ectopic brown adipose tissue ( BAT) interspersed between muscle fibers] of obesity-resistant 129S6/SvEvTac ( 129) and obesity-prone C57BL/6 (B6) mice under conditions of low (LF) and high-fat (HF) feeding. With usual feeding, IBAT mitochondrial UCP1 content and proton conductance were greater in 129 mice than B6. However, with HF feeding, UCP1 and proton conductance increased more in B6 mice. Moreover, with HF feeding GDP-inhibitable proton conductance, specific for UCP1, equaled that seen in the 129 strain. UCP1 expression was substantial in mitochondria from hindlimb muscle tissue ( ectopic BAT) of 129 mice as opposed to B6 but did not increase with HF feeding in either strain. As expected, muscle UCP3 expression increased with HF feeding in both strains but did not differ by strain. Moreover, the proton conductance of mitochondria isolated from hindlimb muscle tissue did not differ by strain or diet. Our data uncover a response to weight gain in obesity-prone ( compared to resistant) mice unrecognized in prior studies that examined only UCP1 mRNA. Obesity-prone mice have the capacity to increase both IBAT UCP1 protein and mitochondrial proton conductance as much or more than obesity-resistant mice. But, this is only achieved only at a higher body mass and, therefore, may be adaptive rather than preventative. Neither obesity-prone nor resistant mice respond to HF feeding by expressing more UCP1 in ectopic BAT within muscle tissue. C1 Univ Iowa, Iowa City, IA USA. Iowa City Vet Affairs Med Ctr, Iowa City, IA USA. Novo Nordisk AS, Malov, Denmark. Univ Ancona, Inst Normal Human Morphol Anat, Ancona, Italy. Harvard Univ, Sch Med, Joslin Diabet Ctr, Div Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Sivitz, WI (reprint author), Univ Iowa Hosp & Clin, Dept Internal Med, Div Endocrinol & Metab, 422GH,200 Hawkins Dr, Iowa City, IA 52242 USA. EM william-sivitz@uiowa.edu FU PHS HHS [D25295] NR 41 TC 24 Z9 25 U1 0 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD NOV PY 2007 VL 293 IS 5 BP R1773 EP R1780 DI 10.1152/ajpregu.00478.2007 PG 8 WC Physiology SC Physiology GA 227OU UT WOS:000250668300001 PM 17761507 ER PT J AU Smoller, JW AF Smoller, Jordan W. TI Genetic boundary violations: Phobic disorders and personality SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Editorial Material ID ANXIETY; RISK C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Smoller, JW (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 185 Campbridge St, Boston, MA 02114 USA. EM jsmoller@hms.harvard.edu NR 8 TC 1 Z9 1 U1 1 U2 1 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 2007 VL 164 IS 11 BP 1631 EP 1633 DI 10.1176/appi.ajp.2007.07081368 PG 3 WC Psychiatry SC Psychiatry GA 229NP UT WOS:000250811200003 PM 17974923 ER PT J AU Bratti, IM Kane, JM Marder, SR AF Bratti, Irene M. Kane, John M. Marder, Stephen R. TI Chronic restlessness with antipsychotics SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID NEUROLEPTIC-INDUCED AKATHISIA; DRUG-INDUCED AKATHISIA; TARDIVE-DYSKINESIA; CONTROLLED-TRIAL; CONVENTIONAL ANTIPSYCHOTICS; SCHIZOPHRENIC-PATIENTS; LEGS SYNDROME; RATING-SCALE; HALOPERIDOL; CLOZAPINE AB Mr. B is a 34-year-old man with a 13-year history of schizophrenia. His early treatment consisted of brief trials of first-generation antipsychotics, which he refused to take for any significant period of time. He was then started on rispericlone at an average of 5 mg/day. Within a few months, he and his mother noticed that he had upper and lower extremity tremor and profound motor restlessness, especially of the legs. These symptoms worsened until Mr. B was taken off rispericlone and started on olanzapine, after which the tremor resolved, but the restlessness persisted. Mr. B's discomfort was so severe that he was unable to sit through a 15-minute medication management appointment without getting up and pacing the room. His mother noted that the restlessness lasted throughout the day, relenting only when he slept. Mr. B stated that he could not stay still for more than a few minutes at a time and that he had an irresistible urge to move, which led him to pace the house and neighborhood until the soles of his feet were bleeding. Mr. B's mother also reported that when the restlessness was at its worst, he was extremely irritable, easily agitated, and sometimes violent. C1 W Los Angels VA, VAHCS, Los Angeles, CA 90073 USA. San Diego Va Ment Illness Res Educ & Clin Ctr, San Diego, CA USA. Zucker Hillside Hosp, Glen Oaks, NY USA. RP Bratti, IM (reprint author), W Los Angels VA, VAHCS, 11301 Wilshire Blvd, B151-H, Los Angeles, CA 90073 USA. EM ibratti@med-net.ucla.edu NR 58 TC 19 Z9 20 U1 2 U2 2 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 2007 VL 164 IS 11 BP 1648 EP 1654 DI 10.1176/appi.ajp.2007.07071150 PG 7 WC Psychiatry SC Psychiatry GA 229NP UT WOS:000250811200008 PM 17974927 ER PT J AU Yehuda, R Friedman, M Rosenbaum, TY Labinsky, E Schmeidler, J AF Yehuda, Rachel Friedman, Michelle Rosenbaum, Talli Y. Labinsky, Ellen Schmeidler, James TI History of past sexual abuse in married observant Jewish women SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID MENTAL-HEALTH; PREVALENCE; ASSAULT; PSYCHOPATHOLOGY; VETERANS; RELIGION AB Objective: The authors examined instances of past sexual abuse and related demographic characteristics in the self-reports of a select group of married observant Jewish women. Methods: Orthodox Jewish married women (N = 380) ages 19 to 58 responded to advertisements asking them to complete an anonymous questionnaire about sexual experiences, including sexual abuse. Results: Sexual abuse was reported by 26% of the respondents surveyed, with 16% reporting abuse occurring by the age of 13. More ultra-Orthodox Jews reported abuse than modern-Orthodox Jews. Women who were raised observant reported significantly less childhood sexual abuse than those who became observant later in life. Sexual abuse was associated with increased treatment-seeking for depression, marital counseling, or other emotional or psychological problems. Conclusion: While observant Jewish women live in a culture defined by a high degree of adherence to specific laws of conduct, including rules designed to regulate sexual contact, sexual abuse of various types still exists among them. C1 James J Peters VA Med Ctr, Psychait OOMH, Bronx, NY 10468 USA. Mt Sinai Sch Med, Dept Psychiat, Div Traumat Stress Studies, New York, NY USA. RP Yehuda, R (reprint author), James J Peters VA Med Ctr, Psychait OOMH, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM rachel.yehuda@.va.gov NR 19 TC 5 Z9 5 U1 0 U2 2 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 2007 VL 164 IS 11 BP 1700 EP 1706 DI 10.1176/appi.ajp.2007.06122030 PG 7 WC Psychiatry SC Psychiatry GA 229NP UT WOS:000250811200016 PM 17974935 ER PT J AU Liu, M Yang, SC Sharma, S Luo, J Cui, XY Peebles, KA Huang, M Sato, M Ramirez, RD Shay, JW Minna, JD Dubinett, SM AF Liu, Ming Yang, Seok-Chul Sharma, Sherven Luo, Jie Cui, Xiaoyan Peebles, Katherine A. Huang, Min Sato, Mitsuo Ramirez, Ruben D. Shay, Jerry W. Minna, John D. Dubinett, Steven M. TI EGFR signaling is required for TGF-beta 1-Mediated COX-2 induction in human bronchial epithelial cells SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article DE cyclooxygenase-2; transforming growth factor-beta 1; epidermal growth factor receptor; lung cancer; Smad3 ID GROWTH-FACTOR RECEPTOR; LUNG-CANCER CELLS; OBSTRUCTIVE PULMONARY-DISEASE; TGF-BETA; CYCLOOXYGENASE-2 EXPRESSION; TRANSFORMING GROWTH-FACTOR-BETA-1; MAP KINASE; INTERFERON-GAMMA; CARCINOMA-CELLS; FACTOR-ALPHA AB Cyclooxygenase-2 (COX-2) is a key enzyme in the production of Prostaglandins and thromboxanes from free arachidonic acid. Increasing evidence suggests that COX-2 plays a role in tumorigenesis. A variety of stimuli induce COX-2 and it is overexpressed in many tumors, including non-small cell lung cancer (NSCLC). We studied the regulation of COX-2 expression in immortalized human bronchial epithelial cells (HBECs) by transforming growth factor-beta 1 (TGF-beta 1) and epidermal growth factor (EGF) because these two growth factors are present in both the pulmonary milieu of those at risk for lung cancer as well as in the tumor microenvironment. EGF significantly enhanced TGF-beta 1-mediated induction of COX-2 and corresponding prostaglandin E2 (PGE2) production. TGF-beta 1 and EGF induced COX-2 at the transcriptional and post-transcriptional levels. EGF receptor (EGFR) inhibition, neutralizing antibody against amphiregulin, or mitogen-activated protein kinase kinase (MEK) inhibition blocked TGF-beta 1-mediated COX-2 induction. COX-2 induction by TGF-beta 1 depended upon Smad3 signaling and required the activity of EGFR or its downstream mediators. Autocrine amphiregulin signaling maintains EGFR in a constitutively active state in HBECs, allowing for COX-2 induction by TGF-beta 1. Thus, EGFR ligands, which are abundant in the pulmonary microenvironment of those at risk for lung cancer, potentiate and are required for COX-2 induction by TGF-beta 1 in HBEC. These findings emphasize the central role of EGFR signaling in COX-2 induction by TGF-PI and suggest that inhibition of EGFR signaling should be investigated further for lung cancer prevention. C1 Univ Calif Los Angeles, Lung Canc Res Program, David Geffen Sch Med, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA. Vet Affairs Greater Los Angeles Healthcare Ctr, Los Angeles, CA USA. Univ Texas, SW Med Ctr, Hamon Ctr Therapeut Oncol Res, Dallas, TX USA. Dallas Vet Affairs Med Ctr, Dallas, TX USA. Univ Texas, SW Med Ctr, Dept Cell Biol, Dallas, TX USA. Univ Calif Los Angeles, Dept Pathol & Lab Med, David Geffen Sch Med, Los Angeles, CA USA. RP Dubinett, SM (reprint author), Univ Calif Los Angeles, Lung Canc Res Program, David Geffen Sch Med, Jonsson Comprehens Canc Ctr, 37-131 CHS,10833 Conte Ave,Room 37-131 CHS, Los Angeles, CA 90095 USA. EM sdubinett@mednet.ucla.edu RI Shay, Jerry/F-7878-2011; Sato, MITSUO/I-7280-2014 FU NCI NIH HHS [P50 CA070907, P50 CA70907, P50 CA90388] NR 67 TC 24 Z9 25 U1 0 U2 1 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD NOV PY 2007 VL 37 IS 5 BP 578 EP 588 DI 10.1165/rcmb.2007-0100OC PG 11 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 228OC UT WOS:000250738200010 PM 17600311 ER PT J AU Goldsztein, H Pletcher, SD Reh, DD Metson, R AF Goldsztein, Hernan Pletcher, Steven D. Reh, Douglas D. Metson, Ralph TI The frontal wishbone: Anatomic and clinical implications SO AMERICAN JOURNAL OF RHINOLOGY LA English DT Article; Proceedings Paper CT Meeting of the Eastern Section of the Triological-Society CY JAN 20-22, 2006 CL Toronto, CANADA SP Triol Soc, Eastern Sect DE frontal recess; frontal recess obstruction; frontal sinus; frontal sinus surgery; frontal sinusitis; intersinus septal cell; wishbone ID INTERSINUS SEPTAL CELL AB Background: The interfrontal septal cell, which often takes the shape of a wishbone on axial CT scan, was first described by Van Alyea more than 50 years ago; however, its potential role in disease of the frontal sinus was only recently recognized. The purpose of this study was to correlate the incidence and dimensions of this "frontal wishbone" (FWB) with the presence of frontal sinus disease. Methods: The dimensions, drainage pathways, and disease state of the FWB were measured in 150 consecutive sinus CT scans performed at a tertiary care referral center. Statistical analysis was performed to correlate the FWB configuration to the presence of frontal sinus disease. Results: A FWB was present in 77.3% of patients. The wishbone drained through a discrete ostium into either the left (54.8%), the right (45.2%), or the bilateral (0.8%)frontal sinuses. In those scans with mucosal thickening or opacification of the frontal sinus (36%), concurrent FWB disease was found in 82%. Patients with a large (>1 cm) FWB in the anterior-posterior dimension were more likely to have a diseased frontal sinus (p = 0.02). Conclusion: The term FWB is used to describe an air cell within the interfrontal septum, which may play a role in the pathogenesis of frontal sinus disease. C1 [Goldsztein, Hernan; Pletcher, Steven D.; Reh, Douglas D.; Metson, Ralph] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Metson, Ralph] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Metson, R (reprint author), Zero Emerson Pl, Boston, MA 02114 USA. EM ralph_metson@meei.harvard.edu NR 6 TC 5 Z9 5 U1 0 U2 1 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 USA SN 1050-6586 J9 AM J RHINOL JI Am. J. Rhinol. PD NOV-DEC PY 2007 VL 21 IS 6 BP 725 EP 728 DI 10.2500/ajr.2007.21.3099 PG 4 WC Otorhinolaryngology SC Otorhinolaryngology GA 244YI UT WOS:000251901000015 PM 18201455 ER PT J AU Georgian-Smith, D Moore, RH Halpern, E Yeh, ED Rafferty, EA D'Alessandro, HA Staffa, M Hall, DA McCarthy, KA Kopans, DB AF Georgian-Smith, Dianne Moore, Richard H. Halpern, Elkan Yeh, Eren D. Rafferty, Elizabeth A. D'Alessandro, Helen Anne Staffa, Mary Hall, Deborah A. McCarthy, Kathleen A. Kopans, Daniel B. TI Blinded comparison of computer-aided detection with human second reading in screening mammography SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE breast cancer; computer-aided detection; mammography; mammography recall rates; screening mammography ID BREAST-CANCER; DETECTION CAD; PROGRAM AB OBJECTIVE. The purpose of this study was to compare a human second reader with computer-aided detection (CAD) for the reduction of false-negative cases by a primary radiologist. We retrospectively reviewed our clinical practice. MATERIALS AND METHODS. We found that 6,381 consecutive screening mammo-grams were interpreted by a primary reader. This radiologist then reinterpreted the studies using CAD ("CAD reader"). A second human reader who was blinded to the CAD results but knowledgeable of the primary reader's findings reviewed the studies, looking for abnormalities not seen by the first reader. RESULTS. Two cancers were called back by the second human reader that were not called back by the CAD reader; however, the CAD system had marked the findings, but they were dismissed by the primary reader. Because of the small numbers, the difference between the CAD and second human reader was not statistically significant. The CAD and human second readers increased the recall rates 6.4% and 7.2% (p = 0.70), respectively, and the biopsy rates 10% and 14.7%. The positive predictive value was 0% (0/3) for the CAD reader and was 40% (2/5) for the human second reader. The relative increases in the cancer detection rate compared with the primary reader's detection rate were 0% for the CAD reader and 15.4% (2/13) for the human second reader (p = 0.50). CONCLUSION. A human second reader or the use of a CAD system can increase the cancer detection rate, but we found no statistical difference between the two because of the small sample size. A possible benefit from a human second reader is that CAD systems can only point to possible abnormalities, whereas a human must determine the significance of the finding. Having two humans review a study may increase detection rates due to interpreter-hence, perceptual-variability and not just increased detection. C1 Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. AVON Breast Ctr, Boston, MA USA. Massachusetts Gen Hosp, Inst Technol Assessment, Dept Radiol, Boston, MA 02114 USA. RP Georgian-Smith, D (reprint author), Brigham & Womens Hosp, Dept Radiol, 75 Francis St, Boston, MA 02115 USA. EM dgeorgiansmith@partners.org NR 20 TC 28 Z9 28 U1 1 U2 3 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 2007 VL 189 IS 5 BP 1135 EP 1141 DI 10.2214/AJR.07.2393 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 225LD UT WOS:000250518500020 PM 17954651 ER PT J AU Bilimoria, KY Bentrem, DJ Tomlinson, JS Merkow, RP Stewart, AK Ko, CY Prystowsky, JB Talamonti, MS AF Bilimoria, Karl Y. Bentrem, David J. Tomlinson, James S. Merkow, Ryan P. Stewart, Andrew K. Ko, Clifford Y. Prystowsky, Jay B. Talamonti, Mark S. TI Quality of pancreatic cancer care at Veterans Administration compared with non-Veterans Administration hospitals SO AMERICAN JOURNAL OF SURGERY LA English DT Article; Proceedings Paper CT 31st Annual Surgical Symposium of the Association-of-VA-Surgeons CY MAY 10-12, 2007 CL Little Rock, AR SP Assoc VA Surg DE national cancer data base; pancreatectomy; pancreatic neoplasms; surgery; veterans administration; medical center ID LONG-TERM SURVIVAL; SURGICAL QUALITY; OPERATIVE MORTALITY; CONSECUTIVE PANCREATICODUODENECTOMIES; DUCTAL ADENOCARCINOMA; IMPROVEMENT PROGRAM; GENERAL-POPULATION; UNITED-STATES; LAST DECADE; RESECTION AB Background: National efforts are underway to monitor the quality of patient care at Veterans Administration (VA) hospitals. The objective of this study was to examine treatment utilization and outcomes for localized pancreatic cancer at VA compared with non-VA hospitals. Methods: Using the National Cancer Data Base, patients with pretreatment clinical stage I/II pancreatic adenocarcinorna were identified. Treatment utilization and outcomes were assessed at VA compared with academic and community hospitals. Results: Of 35,009 patients, 2% were seen at VA, 38% at academic, and 54% at community hospitals. VA hospitals were more likely to use surgery (odds ratio 2.20, 95% confidence interval 1.73-2.79) and to administer adjuvant chemotherapy (odds ratio 1.77, confidence interval 1.28-2.46) compared with community hospitals. Adjusted perioperative mortality and 3-year survival rates after surgery were similar at VA and academic hospitals. Conclusions: For localized pancreatic cancer, patients treated at VA hospitals receive stage-specific treatments and have risk-adjusted perioperative and long-term survival rates that are comparable with those for patients treated at academic centers. (C) 2007 Excerpta Medica Inc. All rights reserved. C1 Northwestern Univ, Feinberg Sch Med, Dept Surg, Chicago, IL 60611 USA. Amer Coll Surg, Dept Surg, Chicago, IL 60611 USA. Univ Calif Los Angeles, Dept Surg, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90095 USA. RP Talamonti, MS (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Surg, 675 N St Clair St,Galter 10-105, Chicago, IL 60611 USA. EM mtalamonti@nmff.org NR 49 TC 14 Z9 14 U1 0 U2 2 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD NOV PY 2007 VL 194 IS 5 BP 588 EP 593 DI 10.1016/j.amjsurg.2007.07.012 PG 6 WC Surgery SC Surgery GA 223GW UT WOS:000250358900003 PM 17936418 ER PT J AU Matthews, RD Anthony, T Kim, LT Wang, J Fitzgibbons, RJ Giobbie-Hurder, A Reda, DJ Itani, KMF Neumayer, LA AF Matthews, Richard D. Anthony, Thomas Kim, Lawrence T. Wang, Jia Fitzgibbons, Robert J., Jr. Giobbie-Hurder, Anita Reda, Domenic J. Itani, Kamal M. F. Neumayer, Leigh A. CA VAC 456 SPI TI Factors associated with postoperative complications and hernia recurrence for patients undergoing inguinal hernia repair: a report from the VA Cooperative Hernia Study Group SO AMERICAN JOURNAL OF SURGERY LA English DT Article; Proceedings Paper CT 31st Annual Surgical Symposium of the Association-of-VA-Surgeons CY MAY 10-12, 2007 CL Little Rock, AR SP Assoc VA Surg DE complications; recurrence; inguinal; herniorrhaphy; lichtenstein; laparoscopic ID RANDOMIZED CONTROLLED-TRIALS; MESH REPAIR; GROIN HERNIA; METAANALYSIS; CONVALESCENCE; HERNIORRHAPHY; SMOKING; PAIN AB Background: We sought to determine perioperative variables predictive of complications or recurrence for patients undergoing surgical repair of inguinal hernias. Patients and Methods: Using data from the Veterans Affairs trial, regression analyses were utilized to identify perioperative factors significantly associated with complications (overall, short-term and longterm), long-term pain, and to develop a risk model for recurrence. Results: Recurrent and scrotal hernias were predictors for short term and overall complications, regardless of technique. Older age and higher Mental Component Score of the SF-36 were associated with higher risk of long term complications in the open group while prostatism and increased body mass index were the significant predictors in the laparoscopic group. Long-term pain complaints decreased as patient.age increased in both groups. Patient and surgeon factors were predictive of recurrence but varied greatly depending on surgical technique. Conclusions: Regardless of technique, scrotal and recurrent hernias were associated with a greater risk of complications and younger patients had more long-term pain. Predictors of recurrence vary based on surgical technique. (C) 2007 Excerpta Medica Inc. All rights reserved. C1 George E Wahlen Salt Lake City VA Hlth Care Syst, Salt Lake City, UT 84148 USA. Univ Utah, Dept Surg, VAMC 112, Salt Lake City, UT 84148 USA. Univ Texas, SW Med Ctr, Dallas, TX 75216 USA. VA N Texas Hlth Care Syst, Dallas, TX 75216 USA. Univ Arkansas Med Sci, Little Rock, AR 72205 USA. Cent Arkansas VA Hlthcare Syst, Little Rock, AR 72205 USA. VA Cooperat Studies Program Coordinating Ctr, Hines, IL 60141 USA. VA Nebraska Western Iowa Hlth Care Syst, Omaha, NE 68105 USA. Creighton Univ, Omaha, NE 68105 USA. Boston Univ, Boston, MA 02130 USA. VA Boston Hlth Care Syst, Boston, MA 02130 USA. RP Neumayer, LA (reprint author), George E Wahlen Salt Lake City VA Hlth Care Syst, 500 Foothill Dr, Salt Lake City, UT 84148 USA. EM leigh.nemayer@hse.utah.edu NR 28 TC 23 Z9 28 U1 1 U2 1 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD NOV PY 2007 VL 194 IS 5 BP 611 EP 617 DI 10.1016/j.amjsurg.2007.08.018 PG 7 WC Surgery SC Surgery GA 223GW UT WOS:000250358900007 PM 17936422 ER PT J AU Chu, D Bakaeen, FG Shenaq, SA Ribati, M Atluri, PV Holmes, SA Berger, DH Huh, J AF Chu, Danny Bakaeen, Faisal G. Shenaq, Salwa A. Ribati, Miran Atluri, Prasad V. Holmes, Sally A. Berger, David H. Huh, Joseph TI Open-heart operations in patients with a spinal cord injury SO AMERICAN JOURNAL OF SURGERY LA English DT Article; Proceedings Paper CT 31st Annual Surgical Symposium of the Association-of-VA-Surgeons CY MAY 10-12, 2007 CL Little Rock, AR SP Assoc VA Surg DE cardiac; surgery; spinal cord injury; outcomes ID CORONARY-ARTERY-DISEASE; CARDIAC ISCHEMIA; RISK-FACTORS; PARAPLEGIA AB Background: The objective of our study was to evaluate the outcomes of open-heart surgery in patients with a spinal cord injury. Methods: A retrospective analysis of all patients (n = 8) with a spinal cord injury who underwent open-heart operations in a single institution from April 1994 to November 2006 was conducted. Results: All patients had a permanent spinal cord injury with levels ranging from T3 to L2 with a mean age of 62 years (range, 47-72). Seven coronary artery bypass operations and 2 aortic valve replacements were performed. The mean cardiac ejection fraction was 44% (range, 20-60). Seventy-five percent of the patients were extubated within 24 hours of the operation. A decubitus ulcer occurred in only I patient. The acute hospital stay averaged 14 days (range, 6-36). One patient died from multiorgan failure on postoperative day 13 giving an in-hospital 30-day mortality of 12.5%. The 5-year survival was 75% with a mean follow-up of 67 months (range,.5-129). Conclusions: Open-heart operations in patients with a spinal cord injury can be performed safely with acceptable early and late outcomes. (C) 2007 Excerpta Medica Inc. All rights reserved. C1 Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Div Cardiothorac Surg, Houston, TX 77030 USA. Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Dept Surg, Houston, TX 77030 USA. Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Dept Anesthesiol, Houston, TX 77030 USA. RP Bakaeen, FG (reprint author), Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Div Cardiothorac Surg, 2002 Holcombe Blvd,OCL 112, Houston, TX 77030 USA. EM dchumd@gmail.com NR 17 TC 3 Z9 4 U1 0 U2 0 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD NOV PY 2007 VL 194 IS 5 BP 663 EP 667 DI 10.1016/j.amjsurg.2007.07.015 PG 5 WC Surgery SC Surgery GA 223GW UT WOS:000250358900016 PM 17936431 ER PT J AU Srivastava, A Odze, RD Lauwers, GY Redston, M Antonioli, DA Glickman, JN AF Srivastava, Amitabh Odze, Robert D. Lauwers, Gregory Y. Redston, Mark Antonioli, Donald A. Glickman, Jonathan N. TI Morphologic features are useful in distinguishing Barrett esophagus from carditis with intestinal metaplasia SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article; Proceedings Paper CT Digestive Disease Week Meeting/107th Annual Meeting of the American-Gastroenterological-Association CY MAY 19-24, 2006 CL Los Angeles, CA SP Amer Gastroenterol Assoc DE Barrett esophagus; intestinal metaplasia; interobserver variability ID HELICOBACTER-PYLORI INFECTION; COLUMNAR-LINED ESOPHAGUS; GASTRIC CARDIA; GASTROESOPHAGEAL JUNCTION; ESOPHAGOGASTRIC JUNCTION; DISTAL ESOPHAGUS; MULTILAYERED EPITHELIUM; CYTOKERATIN SUBSETS; EXPRESSION; REFLUX AB Barrett esophagus (BE) and carditis with intestinal metaplasia (CIM) differ in their risk of malignancy and implications for patient management, but are difficult to distinguish in mucosal biopsies from the gastroesophageal junction region. The present study was performed to evaluate the role of routine morphology in distinguishing BE from CIM in mucosal biopsies and to assess the degree of interobserver variability in recognizing morphologic parameters that are of significance in making this distinction. Several morphologic features, including presence of crypt disarray and atrophy, incomplete and diffuse intestinal metaplasia, multilayered epithelium, squamous epithelium overlying columnar crypts with intestinal metaplasia, hybrid glands, and esophageal glands/ducts, were significantly associated with a diagnosis of BE. The latter 3 features were observed exclusively in BE biopsies. Furthermore, multiple BE-associated morphologic features were often present together in BE but not CIM biopsies. There was substantial agreement (kappa = 0.6) among expert gastrointestinal pathologists for distinguishing BE from CIM even in the absence of clinical/endoscopic information. The interobserver agreement in recognition of BE-associated morphologic features ranged from almost perfect for some features like esophageal glands/ducts (kappa = 0.83) to slight for multilayered epithelium (kappa = 0.17). In conclusion, our findings indicate that several morphologic features are helpful in distinguishing BE from CIM. The combined presence of multiple BE-associated morphologic features can be used in making this distinction with a high degree of accuracy. Larger prospective studies need to be performed to validate these findings and evaluate the reproducibility of this approach in routine clinical practice. C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Glickman, JN (reprint author), Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02114 USA. EM jglickman@partners.org RI Srivastava, Amitabh/A-9386-2009 NR 54 TC 48 Z9 51 U1 0 U2 0 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 2007 VL 31 IS 11 BP 1733 EP 1741 PG 9 WC Pathology; Surgery SC Pathology; Surgery GA 225OL UT WOS:000250527100014 PM 18059231 ER PT J AU Yantiss, RK Panczykowski, A Misdraji, J Odze, RD Rennert, H Chen, YT AF Yantiss, Rhonda K. Panczykowski, Andrea Misdraji, Joseph Odze, Robert D. Rennert, Hanna Chen, Yao-Tseng TI A comprehensive study of nondysplastic and dysplastic serrated polyps of the vermiform appendix SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE BRAF; KRAS; DNA hypermethylation; microsatellite instability; adenoma; hyperplastic polyp; serrated polyp; sessile serrated adenoma ID CPG ISLAND METHYLATION; HYPERPLASTIC POLYPS; COLORECTAL POLYPS; KRAS MUTATIONS; ADENOMAS; BRAF; PATHWAY; COLON; CLASSIFICATION; PHENOTYPE AB Serrated colorectal polyps often show DNA hypermethylation and/or BRAF mutations and have been implicated in the "serrated neoplastic pathway." Although similar lesions occur in the appendix, they have never been systematically investigated. We evaluated a study group of 56 serrated polyps, a control group of 17 mucinous cystadenomas, and 4 adenocarcinomas with adjacent serrated polyps of the appendix to better understand their pathogenesis. The study cases were classified as nondysplastic or dysplastic serrated polyps and evaluated for MLH-1, MSH-2, MGMT, P-catenin, p53, and Ki-67 expression, BRAF and KRAS mutations, and microsatellite instability. Serrated polyps usually occurred in older adults with no sex predilection. Most (59%) lacked dysplasia, but all showed similar molecular features, regardless of the degree of dysplasia present. Decreased MLH-1 (50%, P < 0.001) and/or MGMT (59%, P < 0.001) expression and BRAF (29%, P = 0.007) mutations were significantly more common in serrated polyps, but BRAF mutations were detected in a minority of the extracted DNA in 15/16 cases. Of the 28 cases with decreased MLH-1 expression, none showed high-frequency microsatellite instability. Loss of MLH-1 (25 %) or MGMT (50%) expression and BRAF or KRAS mutations (50%) were inconsistently present in adenocarcinomas and were not identified in combination in any cases. We conclude that molecular features of the "serrated neoplastic pathway" are present with similar frequencies among dysplastic and nondysplastic serrated appendiceal polyps and are not highly prevalent in adjacent carcinomas. These features, including BRAF mutations, may be more closely related to a serrated morphology in appendiceal polyps rather than biologically important changes. C1 Cornell Univ, Weill Med Coll, Dept Pathol & Lab Med, New York, NY 10021 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Yantiss, RK (reprint author), Cornell Univ, Weill Med Coll, Dept Pathol & Lab Med, 525 E 68th St, New York, NY 10021 USA. EM rhy2001@med.cornell.edu NR 26 TC 22 Z9 22 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD NOV PY 2007 VL 31 IS 11 BP 1742 EP 1753 PG 12 WC Pathology; Surgery SC Pathology; Surgery GA 225OL UT WOS:000250527100015 PM 18059232 ER PT J AU Zembowicz, A Knoepp, SM Bei, T Stergiopoulos, S Eng, C Mihm, MC Stratakis, CA AF Zembowicz, Artur Knoepp, Stewart M. Bei, Thalia Stergiopoulos, Sotirios Eng, Charis Mihm, Martin C. Stratakis, Constantine A. TI Loss of expression of protein kinase A regulatory subunit 1 alpha in pigmented epithelioid melanocytoma but not in melanoma or other melanocytic lesions SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE pigmented epithelioid melanocytoma; nevus; melanoma; equine melanotic disease; epithelioid blue nevus; Carney complex; protein kinase A regulatory subunit 1 alpha ID ANIMAL-TYPE MELANOMA; CARNEY COMPLEX; BLUE NEVUS; REGULATORY SUBUNIT; MALIGNANT-MELANOMA; PRKAR1A GENE; MOUSE MODEL; I-ALPHA; TUMORS; MUTATIONS AB Pigmented epithelioid melanocytoma (PEM) is a recently described entity comprising most cases previously described as "animal-type melanoma" and epithelioid blue nevus (EBN) occurring in patients with the multiple neoplasia syndrome Carney complex (CNC). Mutations of the protein kinase A regulatory subunit type 1 alpha (R1 alpha) (coded by the PRKAR1A gene) are found in more than half of CNC patients. In this study, we investigated whether PEM and EBN are related at the molecular level, and whether changes in the PRKAR1A gene status and the expression of the R1 alpha protein may be involved in the pathogenesis of PEM and other melanocytic lesions. Histologic analysis of hematoxylin and eosin-stained sections and immunohistochemistry (IHC) with R1 alpha antibody were performed on 34 sporadic PEMs, 8 CNC-associated PEMs from patients with known PRKAR1A mutations, 297 benign and malignant melanocytic tumors (127 conventional sections of 10 compound nevi, 10 Spitz nevi, 5 deep-penetrating nevi, 5 blue nevi, 6 cellular blue nevi, 2 malignant blue nevi, 3 lentigo maligna, and 86 melanomas of various types); in addition, 170 tissue microarray sections consisting of 35 benign nevi, 60 primary melanomas, and 75 metastatic melanomas, and 5 equine dermal melanomas, were examined. Histologic diagnoses were based on preexisting pathologic reports and were confirmed for this study. DNA studies [loss of heterozygosity (LOH) for the 17q22-24 locus and the PRKAR1A gene sequencing] were performed on 60 melanomas and 7 PEMs. IHC showed that R I a was expressed in all but one core from tissue microarrays (169/170), and in all 127 melanocytic lesions evaluated in conventional sections. By contrast, R1 alpha was not expressed in the 8 EBN from patients with CNC and PRKAR1A mutations. Expression of R1 alpha was lost in 28 of 34 PEMs (82%). R1 alpha was expressed in the 5 equine melanomas studied. DNA studies correlated with IHC findings: there were no PRKAR1A mutations in any of the melanomas studied and the rate of LOH for 17q22-24 was less than 7%; 5 of the 7 PEMs showed extensive 17q22-24 LOH but no PRKAR1A mutations. The results support the concept that PEM is a distinct melanocytic tumor occurring in a sporadic setting and in the context of CNC. They also suggest that PEM differs from melanomas in equine melanotic disease, further arguing that the term animal-type melanoma may be a misnomer for this group of lesions. Loss of expression of R1 alpha offers a useful diagnostic test that helps to distinguish PEM from lesions that mimic it histologically. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA USA. NICHHD, NIH, Sect Endocrinol & Genet, Bethesda, MD 20892 USA. Taussig Canc Ctr, Cleveland, OH USA. Cleveland Clin Fdn, Lerner Res Inst, Genome Med Inst, Cleveland, OH 44195 USA. RP Zembowicz, A (reprint author), Lahey Clin Fdn, Dept Pathol, 41 Mall Rd, Burlington, MA 01805 USA. EM dr.zembowicz@DermatopathologyConsultations.com FU Intramural NIH HHS NR 30 TC 50 Z9 51 U1 1 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 2007 VL 31 IS 11 BP 1764 EP 1775 PG 12 WC Pathology; Surgery SC Pathology; Surgery GA 225OL UT WOS:000250527100018 PM 18059235 ER PT J AU Murata, K Fox-Talbot, K Qian, Z Takahashi, K Stahl, GL Baldwin, WM Wasowska, BA AF Murata, K. Fox-Talbot, K. Qian, Z. Takahashi, K. Stahl, G. L. Baldwin, W. M., III Wasowska, B. A. TI Synergistic deposition of c4d by complement-activating and non-activating antibodies in cardiac transplants SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE alloantibodies; allograft; antibody-mediated rejection; C4d; MBL ID MANNOSE-BINDING LECTIN; KIDNEY-TRANSPLANTATION; MEDIATED REJECTION; ENDOTHELIAL-CELLS; HUMORAL REJECTION; HLA ALLOANTIBODIES; FC-RECEPTORS; ALLOGRAFTS; DIAGNOSIS; ISCHEMIA AB The role of non-complement-activating alloantibodies in humoral graft rejection is unclear. We hypothesized that the non-complement-activating alloantibodies synergistically activate complement in combination with complement-activating antibodies. B10.A hearts were transplanted into immunoglobulin knock out (Ig-KO) mice reconstituted with monoclonal antibodies to MHC class I antigens. In allografts of unreconstituted Ig-KO recipients, no C4d was detected. Similarly, reconstitution with IgG1 or low dose IgG2b alloantibodies did not induce C4d deposition. However, mice administered with a low dose of IgG2b combined with IgG1 had heavy linear deposits of C4d on vascular endothelium. C4d deposits correlated with decreased graft survival. To replicate this synergy in vitro, mononuclear cells from B10.A mice were incubated with antibodies to MHC class I antigens followed by incubation in normal mouse serum. Flow cytometry revealed that both IgG2a and IgG2b synergized with IgG1 to deposit C4d. This synergy was significantly decreased in mouse serum deficient in mannose binding lectin (MBL) and in serum deficient in C1q. Reconstitution of MBL-A/C knock out (MBL-KO) serum with C1q-knock out (C1q-KO) serum reestablished the synergistic activity. This suggests a novel role for non-complement-activating alloantibodies and MBL in humoral rejection. C1 Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Anesthesiol Perioperat & Pain Med, Ctr Expt Therapeut & Reperfus Injury, Boston, MA 02115 USA. RP Baldwin, WM (reprint author), Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA. EM wbaldwin@jhmi.edu; bwasowsk@jhmi.edu FU NHLBI NIH HHS [R01-HL56068, P01-HL56091, R01-HL52886, R01-HL63948]; NIAID NIH HHS [R01-AI42387]; NIDCR NIH HHS [P50-DE016191, R01-DE017821] NR 49 TC 45 Z9 46 U1 0 U2 1 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 2007 VL 7 IS 11 BP 2605 EP 2614 DI 10.1111/j.1600-6143.2007.01971.x PG 10 WC Surgery; Transplantation SC Surgery; Transplantation GA 219IH UT WOS:000250077600023 PM 17868071 ER PT J AU Harris, JB LaRocque, R Chowdhurry, F Kahn, A Logvinenko, T Faruque, AS Ryan, ET Qadri, F Calderwood, S AF Harris, Jason B. LaRocque, Regina Chowdhurry, Fahima Kahn, Ashraful Logvinenko, Tanya Faruque, Abu S. Ryan, Edward T. Qadri, Firdausi Calderwood, Stephen TI Susceptibility to Vibrio cholerae infection in a cohort of household contacts of patients with cholera in Bangladesh SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 04-08, 2007 CL Philadelphia, PA SP Amer Soc Trop Med & Hyg C1 [Harris, Jason B.; LaRocque, Regina; Logvinenko, Tanya; Ryan, Edward T.; Calderwood, Stephen] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Chowdhurry, Fahima; Kahn, Ashraful; Faruque, Abu S.; Qadri, Firdausi] Int Ctr Diarrhoel 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 2007 VL 77 IS 5 SU S MA 18 BP 5 EP 6 PG 2 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 228UN UT WOS:000250758200019 ER PT J AU Borad, AJ Allison, G Khan, WA Kane, AV Rogers, K Karim, MM Ahmed, S Hibberd, PL Calderwood, SB Ryan, ET Ward, HD AF Borad, Anoli J. Allison, Geneve Khan, Wasif A. Kane, Anne V. Rogers, Kathleen Karim, Mohammad M. Ahmed, Sabeena Hibberd, Patricia L. Calderwood, Stephen B. Ryan, Edward T. Ward, Honorine D. TI Serum antibody responses to CP27, an immunodominant Cryptosporidium spp. antigen in Bangladeshi children with diarrhea and cryptosporidiosis SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 04-08, 2007 CL Philadelphia, PA SP Amer Soc Trop Med & Hyg C1 [Borad, Anoli J.; Allison, Geneve; Kane, Anne V.; Rogers, Kathleen; Hibberd, Patricia L.; Ward, Honorine D.] Tufts Univ New England Med Ctr, Boston, MA USA. [Khan, Wasif A.; Karim, Mohammad M.; Ahmed, Sabeena] Int Ctr Diarrhoeal Dis Res, Dhaka, Bangladesh. [Calderwood, Stephen B.; Ryan, Edward T.] Massachusetts Gen Hosp, Boston, MA 02114 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 2007 VL 77 IS 5 SU S MA 609 BP 174 EP 174 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 228UN UT WOS:000250758201071 ER PT J AU Anstead, GM Zhang, Q Melby, PC AF Anstead, Gregory M. Zhang, Qiong Melby, Peter C. TI Adiponectin and leptin - Yin and Yang mediators of the macrophage inflammatory response, dependent on host nutritional status SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 04-08, 2007 CL Philadelphia, PA SP Amer Soc Trop Med & Hyg C1 S Texas Vet Healthcare Syst, San Antonio, TX 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 2007 VL 77 IS 5 SU S MA 739 BP 212 EP 212 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 228UN UT WOS:000250758201200 ER PT J AU Kelly, JX Smilkstein, M Winter, R Doclean, R Ager, A Hinrichs, D Riscoe, M AF Kelly, Jane X. Smilkstein, Martin Winter, Rolf Doclean, Rosie Ager, Arba Hinrichs, Dave Riscoe, Mike TI New insight on orally-active acridone antimalarials: Structural and functional diversity SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 56th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY NOV 04-08, 2007 CL Philadelphia, PA SP Amer Soc Trop Med & Hyg C1 [Kelly, Jane X.; Smilkstein, Martin; Winter, Rolf; Doclean, Rosie; Hinrichs, Dave; Riscoe, Mike] Portland VA Med Ctr, Portland, OR USA. [Ager, Arba] Univ Miami, Miami, FL 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 2007 VL 77 IS 5 SU S MA 823 BP 236 EP 236 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 228UN UT WOS:000250758201281 ER PT J AU Kelly, EW Solt, K Raines, DE AF Kelly, Elizabeth W. Solt, Ken Raines, Douglas E. TI Volatile aromatic Anesthetics variably impact human gamma-aminobutyric acid type a receptor function SO ANESTHESIA AND ANALGESIA LA English DT Article ID ALPHA(1)BETA(2)GAMMA(2L) GABA(A) RECEPTORS; NONHALOGENATED ALKANE ANESTHETICS; D-ASPARTATE RECEPTORS; GATED ION CHANNELS; GENERAL-ANESTHETICS; GLYCINE RECEPTORS; DIRECT ACTIVATION; MODULATION; SITES; HEXAFLUOROBENZENE AB The gamma-aminobutyric acid type A (GABA(A)) and N-methyl-D-aspartate (NMDA) receptors are important inhibitory and excitatory neurotransnmitter receptors, respectively, in the central nervous system. At the concentrations required to produce immobility in the face of a noxious stimulus, volatile aromatic anesthetics inhibit NMDA receptors to varying degrees, strongly suggesting that they also act at other targets to produce immobilization. In this study, we sought to assess the potential role that GABAA receptors play in mediating the behavioral actions of volatile aromatic anesthetics. METHODS: Electrophysiological techniques were used to quantify the effects of eight volatile aromatic anesthetics and three clinical anesthetics on currents mediated by alpha(1)beta(2)gamma(2)_GABA(A) receptors expressed in Xenopus oocytes. RESULTS: At equivalent minimal alveolar anesthetic concentration multiples, volatile aromatic anesthetics vary widely in the degrees to which they enhance GABAA receptor-mediated currents elicited by low concentrations of GABA. In general, anesthetics that inhibit NMDA receptors most, enhanced GABA, receptors least. This reciprocal relationship between anesthetic potency on GABA, versus NMDA receptors was also observed for the clinical anesthetics isoflurane, halothane, and cyclopropane. Studies using a range of GABA concentrations indicated that volatile aromatic anesthetics enhance GABAA receptor activity by shifting the open-close (gating) equilibrium towards the open channel state. CONCLUSIONS: These findings suggest that GABAA receptors contribute variably to the behavioral actions of volatile anesthetics and imply that the molecular determinants of anesthetic action on NMDA and GABA, receptors are distinctly different. (Anesth Analg 2007;105:1287-92) C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02114 USA. RP Raines, DE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, 55 Fruit St,Clin Bldg 3, Boston, MA 02114 USA. EM draines@partners.org FU NIGMS NIH HHS [P01-GM58448, T32-GM07592] NR 29 TC 12 Z9 14 U1 0 U2 2 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 2007 VL 105 IS 5 BP 1287 EP 1292 DI 10.1213/01.ane.0000282829.21797.97 PG 6 WC Anesthesiology SC Anesthesiology GA 222SN UT WOS:000250317500020 PM 17959956 ER PT J AU Sullivan, AF Schatz, M Wenzel, SE Vanderweil, SG Camargo, CA AF Sullivan, Ashley F. Schatz, Michael Wenzel, Sally E. Vanderweil, Stefan G. Camargo, Carlos A., Jr. TI A profile of US asthma centers, 2006 SO ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY LA English DT Article ID EMERGENCY-DEPARTMENT; CARE; OUTCOMES; TRIAL; ROOM AB Background: Asthma is a significant public health problem that results in 1.8 million annual emergency department (ED) visits. Many ED visits may be prevented with specialized asthma care. Objective: To describe US asthma centers with a long-term goal of exploring their potential role in improving outcomes for ED patients with acute asthma. Methods: We conducted initial online surveys in 2004. One survey identified asthma centers and their directors through reports by emergency medicine researchers and fellowship directors (allergy/immunology, pulmonary, and critical care) at US hospitals. A second survey asked asthma center directors to describe their asthma center. Follow-up surveys were conducted 2 years later in 2006. Results: Eighty-seven (49%) of the 177 hospitals surveyed have asthma clinics. Although spirometry was available on the day of the visit at all asthma centers surveyed in 2006, only 21% (95 % confidence interval, 11 %-34%) of sites reported that at least 90% of visits per week included a spirometry test. Only one quarter (26%; 95% confidence interval, 15%-40%) of asthma centers reported that at least 90% of patients undergo a skin or blood test for environmental allergens during I of their visits. Half of center directors (53%) were unsure of the approximate number of annual ED visits for acute asthma at their hospital. No significant measured changes were noted in asthma centers between 2004 and 2006. Conclusions: Asthma centers are heterogenous, with different services available. Although challenges remain, collaboration between EDs and asthma centers may contribute to improved asthma outcomes and merits further study. C1 Massachusetts Gen Hosp, Dept Emergency Med, EMNet Coordinating Ctr, Boston, MA 02114 USA. Kaiser Permanente Med Ctr, Dept Allergy, San Diego, CA USA. Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. RP Camargo, CA (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, EMNet Coordinating Ctr, 326 Cambridge St,Suite 410, Boston, MA 02114 USA. EM ccamargo@partners.org NR 20 TC 10 Z9 10 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 2007 VL 99 IS 5 BP 419 EP 423 PG 5 WC Allergy; Immunology SC Allergy; Immunology GA 231IA UT WOS:000250938900007 PM 18051211 ER PT J AU Oren, E Banerji, A Clark, S Camargo, CA AF Oren, Eyal Banerji, Aleena Clark, Sunday Camargo, Carlos A., Jr. TI Food-induced anaphylaxis and repeated epinephrine treatments SO ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY LA English DT Article AB Background: Research on the use of more than 1 dose of epinephrine in the treatment of food-induced anaphylaxis is limited. Objective: To perform a medical record review to examine the frequency of repeated epinephrine treatments in patients presenting with food-induced anaphylaxis to the emergency department (ED). Methods: We reviewed 39 medical records of patients who presented with food-induced allergic reactions to the Massachusetts General Hospital ED during a 1 -year period. The analysis focused on the timing of the onset of symptoms and on the number of epinephrine treatments given before and during the ED visit. Results: Of the 39 patients, 34 had an acute food-induced allergic reaction. Nineteen had anaphylaxis. Twelve patients with anaphylaxis (63%; 95% confidence interval, 38%-84%) received at least 1 dose of epinephrine, and 3 (16%; 95% confidence interval, 3%-40%) were given 2 doses. Although statistical analysis was not possible, repeated epinephrine treatment occurred in patients with anaphylaxis to peanut or tree nut and hypotension. There was no apparent association between time from ingestion of the causative agent to epinephrine treatment(s). Conclusions: Of patients presenting to the ED with food-induced anaphylaxis, approximately 16% were treated with 2 doses of epinephrine. This study supports the recommendation that patients at risk for food-induced anaphylaxis carry 2 doses of epinephrine. Further study is needed to confirm these results and to expand them to patients who do not present to the ED because that group may have a lower frequency of epinephrine use. C1 Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. New York Presbyterian Hosp, New York, NY USA. Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Oren, E (reprint author), Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, 55 Fruit St,Cox 201, Boston, MA 02114 USA. EM eoren1@yahoo.com NR 10 TC 41 Z9 41 U1 0 U2 1 PU AMER COLL ALLERGY ASTHMA IMMUNOLOGY PI ARLINGTON HTS PA 85 WEST ALGONQUIN RD SUITE 550, ARLINGTON HTS, IL 60005 USA SN 1081-1206 J9 ANN ALLERG ASTHMA IM JI Ann. Allergy Asthma Immunol. PD NOV PY 2007 VL 99 IS 5 BP 429 EP 432 PG 4 WC Allergy; Immunology SC Allergy; Immunology GA 231IA UT WOS:000250938900009 PM 18051213 ER PT J AU Pines, JM Locallo, AR Hollander, JE Baxt, WG Lee, H Phillips, C Metlay, JP AF Pines, Jesse M. Locallo, A. Russell Hollander, Judd E. Baxt, William G. Lee, Hol Phillips, Carolyn Metlay, Joshua P. TI The impact of emergency department crowding measures on time to antibiotics for patients with community-acquired pneumonia SO ANNALS OF EMERGENCY MEDICINE LA English DT Article ID LENGTH-OF-STAY; MYOCARDIAL-INFARCTION; AMBULANCE DIVERSION; CARE; QUALITY; ACCESS; PERFORMANCE; CAPACITY; MEDICINE; OUTCOMES AB Study objective: We seek to determine the impact of emergency department (ED) crowding on delays in antibiotic administration for patients with community-acquired pneumonia. Methods: We performed a retrospective cohort study of adult patients admitted with community-acquired pneumonia from January 1, 2003, to April 31, 2005, at a single, urban academic ED. The main outcome was a delay (> 4 hours from arrival) or nonreceipt of antibiotics in the ED. Eight ED crowding measures were assigned at triage. Multivariable regression and bootstrapping were used to test the adjusted impact of ED crowding measures of delayed (or no) antibiotics. Predicted probabilities were then calculated to assess the magnitude of the impact of ED crowding on the probability of delayed (or no) antibiotics. Results: In 694 patients, 44% (95% confidence interval [CI] 40% to 48%) received antibiotics within 4 hours and 92% (95% CI 90% to 94%) received antibiotics in the ED. Increasing levels of ED crowding were associated with delayed (or no) antibiotics, including waiting room number (odds ratio [OR] 1.05 for each additional waiting room patient [95% CI 1.01 to 1.10]) and recent ED length of stay for admitted patients (OR 1.14 for each additional hour [95% CI 1.04 to 1.25]). When the waiting room and recent length of stay were both at the lowest quartiles (ie, not crowded), the predicted probability of delayed (or no) antibiotics within 4 hours was 31% (95% CI 21% to 42%); when both were at the highest quartiles, the predicted probability was 72% (95% CI 61% to 81%). Conclusion: ED crowding is associated with delayed and nonreceipt of antibiotics in the ED for patients admitted with community-acquired pneumonia. C1 Univ Penn, Sch Med, Dept Emergency Med, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Univ Penn, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Leonard Davis Inst Hlth Econ, Philadelphia, PA 19104 USA. Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. RP Pines, JM (reprint author), 3400 Spruce St,Ground Ravdin, Philadelphia, PA 19104 USA. EM pinesjes@uphs.upenn.edu OI Hollander, Judd/0000-0002-1318-2785 NR 34 TC 140 Z9 142 U1 0 U2 7 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD NOV PY 2007 VL 50 IS 5 BP 510 EP 516 DI 10.1016/j.annemergmed.2007.07.021 PG 7 WC Emergency Medicine SC Emergency Medicine GA 227OV UT WOS:000250668400005 PM 17913298 ER PT J AU Calabrese, LH Molloy, ES Singhal, AB AF Calabrese, Leonard H. Molloy, Eamonn S. Singhal, Aneesh B. TI Primary central nervous system vasculitis: Progress and questions SO ANNALS OF NEUROLOGY LA English DT Editorial Material ID PRIMARY ANGIITIS; ANGIOPATHY; SUBSET C1 Cleveland Clin, Dept Rheumat & Immunol Dis, Cleveland, OH 44106 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Stroke Res, Boston, MA USA. RP Calabrese, LH (reprint author), Cleveland Clin, Dept Rheumat & Immunol Dis, Cleveland, OH 44106 USA. FU NINDS NIH HHS [P50NS051343, R01NS051412] NR 11 TC 18 Z9 18 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 2007 VL 62 IS 5 BP 430 EP 432 DI 10.1002/ana.21283 PG 3 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 237NY UT WOS:000251383300002 PM 18041087 ER PT J AU Ro, T Farne, A Johnson, RM Wedeen, V Chu, ZL Wang, ZYJ Hunter, JV Beauchamp, MS AF Ro, Tony Farne, Alessandro Johnson, Ruth M. Wedeen, Van Chu, Zili Wang, Zhiyue J. Hunter, Jill V. Beauchamp, Michael S. TI Feeling sounds after a thalamic lesion SO ANNALS OF NEUROLOGY LA English DT Article ID INTERHEMISPHERIC NEURAL SUMMATION; AUDITORY-VISUAL SYNESTHESIA; ANTI-EXTINCTION; SYNAESTHESIA; BRAIN; COLOR; VISION; HUMANS; CONNECTIONS; BINDING AB Objective: The ventrolateral nucleus of the thalamus (VL), based on its connectivity with the cerebellum and motor cortex, has long been considered to be involved with motor functions. We show that the human VL also plays a prominent role in sensory processing. Methods: Structural magnetic resonance imaging and diffusion tensor imaging were used to localize a small lesion restricted to the right VL in a patient with contralesional sensory processing deficits. Systematic assessments of anatomic brain organization and behavioral measurements of somatosensory and visual processing were conducted at several time points after stroke. Results: Initially, the patient was more likely to detect events on the contralesional side when a simultaneous ipsilesional event was presented within the same, but not different, sensory modality. This perceptual phenomenon, which we refer to as unisensory antiextinction, persisted for several months before transforming into a form of synesthesia in which auditory stimuli produced tactile percepts. Tractography performed on the diffusion tensor imaging data showed altered connections from the lesioned thalamus to the cerebral cortex, suggesting a neural basis for these sensory changes. Interpretation: These results demonstrate a role for the VL in sensory processing and suggest that reorganization of thalamocortical axonal connectivity can lead to major changes in perception. C1 Rice Univ, Dept Psychol, Houston, TX 77005 USA. Baylor Coll Med, Dept Phys Med & Rehabil, Houston, TX 77030 USA. Inst Natl Sante & Rech Med, U864, Bron, France. Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA USA. Baylor Coll Med, Dept Radiol, Houston, TX 77030 USA. Texas Childrens Hosp, Houston, TX 77030 USA. Univ Texas Houston, Hlth Sci Ctr, Dept Neurobiol & Anat, Houston, TX USA. RP Ro, T (reprint author), Rice Univ, Dept Psychol, MS25,6100 Main St, Houston, TX 77005 USA. EM tro@rice.edu RI Wang, Zhiyue/L-3851-2014; Farne', Alessandro/G-1238-2015; OI Wang, Zhiyue/0000-0002-5649-2900; Farne', Alessandro/0000-0001-5769-3491; Beauchamp, Michael/0000-0002-7599-9934 FU NIMH NIH HHS [R03 MH64606] NR 49 TC 45 Z9 45 U1 2 U2 8 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 2007 VL 62 IS 5 BP 433 EP 441 DI 10.1002/ana.21219 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 237NY UT WOS:000251383300003 PM 17893864 ER PT J AU Monje, ML Vogel, H Masek, M Ligon, KL Fisher, PG Palmer, TD AF Monje, Michelle L. Vogel, Hannes Masek, Marilyn Ligon, Keith L. Fisher, Paul G. Palmer, Theo D. TI Impaired human hippocampal neurogenesis after treatment for central nervous system SO ANNALS OF NEUROLOGY LA English DT Article ID THERAPEUTIC IRRADIATION; SYNAPTIC PLASTICITY; DENTATE GYRUS; ADULT BRAIN; RADIATION; TUMORS; INJURY; RAT AB The effects of cancer treatments such as cranial radiation and chemotherapy on human hippocampal neurogenesis remain unknown. In this study, we examine neuropathological markers of neurogenesis and inflammation in the human hippocampus after treatment for acute myelogenous leukemia or medulloblasroma. We demonstrate a persistent radiation-induced microglial inflammation that is accompanied by nearly complete inhibition of neurogenesis after cancer treatment. These findings are consistent with preclinical animal studies and suggest potential therapeutic strategies. C1 Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Stanford Univ Hosp & Clin, Dept Pathol, Stanford, CA USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Childrens Hosp Boston, Dept Pathol, Boston, MA USA. Stanford Univ Hosp & Clin, Dept Neurol, Stanford, CA USA. Stanford Univ Hosp & Clin, Dept Neurosurg, Stanford, CA USA. RP Monje, ML (reprint author), Brigham & Womens Hosp, Dept Neurol, 75 Francis St, Boston, MA 02115 USA. EM mmonje@partners.org FU NIMH NIH HHS [MH071472] NR 22 TC 118 Z9 119 U1 1 U2 5 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 2007 VL 62 IS 5 BP 515 EP 520 DI 10.1002/ana.21214 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 237NY UT WOS:000251383300012 PM 17786983 ER PT J AU Smith, EE Vijyappa, M Wendell, L Rosand, J Greenberg, SM AF Smith, Eric E. Vijyappa, Madhu Wendell, Lauren Rosand, Jon Greenberg, Steven M. TI Abnormal visual evoked flow response suggests decreased vascular reactivity in humans with cerebral amyloid angiopathy SO ANNALS OF NEUROLOGY LA English DT Meeting Abstract CT 132nd Annual Meeting of the American-Neurological-Association CY OCT 07-10, 2007 CL Washington, DC SP Amer Neurol Assoc C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Smith, Eric/C-5443-2012 OI Smith, Eric/0000-0003-3956-1668 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 2007 VL 62 IS 5 BP 538 EP 538 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 237NY UT WOS:000251383300037 ER PT J AU Grimm, SA Pulido, JS Jahnke, K Schiff, D Hall, AJ Shenkier, TN Siegal, T Doolittle, ND Batchelor, T Herrlinger, U Neuwelt, EA Laperriere, N Chamberlain, MC Blay, JY Ferreri, AJM Omuro, AMP Thiel, E Abrey, LE AF Grimm, S. A. Pulido, J. S. Jahnke, K. Schiff, D. Hall, A. J. Shenkier, T. N. Siegal, T. Doolittle, N. D. Batchelor, T. Herrlinger, U. Neuwelt, E. A. Laperriere, N. Chamberlain, M. C. Blay, J. Y. Ferreri, A. J. M. Omuro, A. M. P. Thiel, E. Abrey, L. E. CA Int Extranodal Lymphoma Study Grp TI Primary intraocular lymphoma: an international primary central nervous system lymphoma collaborative group report SO ANNALS OF ONCOLOGY LA English DT Article DE ocular lymphoma; primary CNS lymphoma ID RETICULUM-CELL SARCOMA; CLINICAL-FEATURES; OCULAR LYMPHOMA; MANAGEMENT; DIAGNOSIS; INVOLVEMENT; WORKSHOP; OUTCOMES AB Background: Primary intraocular lymphoma (PIOL) is an uncommon subset of primary central nervous system lymphoma. Because it is rare and difficult to diagnose, the natural history and optimal management are unknown. Patients and methods: A retrospective study of 83 HIV negative, immunocompetent PIOL patients was assembled from 16 centers in seven countries. Results: Median age at diagnosis was 65. Median ECOG performance status was 0. Presenting symptoms included blurred vision, decreased visual acuity, and floaters. Median time to diagnosis was 6 months. Diagnosis was made by vitrectomy (74), choroidal/retinal biopsy (6) and ophthalmic exam (3). Eleven percent had positive CSF cytology. Initial treatment was categorized as focal in 23 (intra-ocular methotrexate, ocular radiotherapy) or extensive in 53 (systemic chemotherapy, whole brain radiotherapy). Six received none; details are unknown in one. Forty-seven relapsed: brain 47%, eyes 30%, brain and eyes 15%, and systemic 8%. Median time to relapse was 19 months. Focal therapy alone did not increase risk of brain relapse. Median progression free (PFS) and overall survival (OS) were 29.6 and 58 months, respectively, and unaffected by treatment type. Conclusion: Treatment type did not affect relapse pattern, median PFS or OS. Focal therapy may minimize treatment toxicity without compromising disease control. C1 [Grimm, S. A.; Abrey, L. E.] Mem Sloan Kettering Canc Ctr, Dept Neurol, New York, NY 10021 USA. [Pulido, J. S.] Mayo Clin, Rochester, MN 55905 USA. [Jahnke, K.] Charite Univ Med Berlin, Berlin, Germany. [Hall, A. J.] Univ Virginia, Charlottesville, VA USA. [Hall, A. J.] Royal Melbourne Hosp, Melbourne, Vic, Australia. [Hall, A. J.] Royal Victorian Eye & Ear Hosp, Melbourne, Vic 3002, Australia. [Shenkier, T. N.] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. [Siegal, T.] Hadassah Hebrew Univ Hosp, Jerusalem, Israel. [Doolittle, N. D.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Batchelor, T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Herrlinger, U.] Univ Tubingen, Tubingen, Germany. [Neuwelt, E. A.] Portland VA Med Ctr, Portland, OR USA. [Laperriere, N.] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. [Chamberlain, M. C.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Omuro, A. M. P.] Hosp Pitie Salpetriere, Paris, France. RP Abrey, LE (reprint author), Mem Sloan Kettering Canc Ctr, Dept Neurol, 1275 York Ave, New York, NY 10021 USA. EM abreyl@mskcc.org RI Ferreri, Andres Jose Maria/A-6662-2013; Blay, Jean-Yves/N-3966-2016 OI Ferreri, Andres Jose Maria/0000-0001-9606-6124; Blay, Jean-Yves/0000-0001-7190-120X NR 17 TC 71 Z9 73 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD NOV PY 2007 VL 18 IS 11 BP 1851 EP 1855 DI 10.1093/annonc/mdm340 PG 5 WC Oncology SC Oncology GA 245UD UT WOS:000251963400013 PM 17804469 ER PT J AU Burns, JA Kobler, JB Heaton, JT Lopez-Guerra, G Anderson, RR Zeitels, SM AF Burns, James A. Kobler, James B. Heaton, James T. Lopez-Guerra, Gerardo Anderson, R. Rox Zeitels, Steven M. TI Thermal damage during thulium laser dissection of laryngeal soft tissue is reduced with air cooling: Ex vivo calf model study SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article; Proceedings Paper CT 87th Annual Meeting of the American-Broncho-Esophagological-Association CY APR 26-27, 2007 CL San Diego, CA SP Amer Broncho Esophagol Assoc DE cooling; dysphonia; hoarseness; laryngoscopy; laser cutting; thulium laser ID CLINICAL EXPERIENCE; SURGERY; CANCER; CO2-LASER; MANAGEMENT; LESIONS; FIBER AB Objectives: The 2-mu m-wavelength thulium laser has recently been shown to be an effective cutting instrument in endolaryngeal surgery, although there is increased thermal trauma as compared with the carbon dioxide laser. This study investigated temperature changes and thermal trauma during thulium laser dissection of laryngeal tissue, with and without air cooling, in an ex vivo model. Methods: A continuous-wave thulium laser (400-mu m fiber, 4-W continuous power, 4-second duration) was used to incise 10 calf vocal folds. Paired cooled and uncooled cuts were made in each fold with a dermatologic cooling device. A thermistor inserted into the glottic subepithelium was used to measure tissue temperatures. Thermal damage was analyzed histologically by measuring the depth of the zone of lactate dehydrogenase inactivation surrounding the mucosal incision. Results: The initial vocal fold temperature averaged 24.3 degrees C without cooling and 4.4 degrees C with cooling. The peak temperature during cutting averaged 59.1 degrees C without cooling and 28.0 degrees C with cooling. The thermal damage zone surrounding the cooled incisions was approximately 27% less than that surrounding the uncooled incisions. Conclusions: Air cooling can reduce the extent of thermal trauma associated with thulium laser surgery of the vocal folds, and the high-temperature plume. generated during laser cutting is effectively cleared. C1 Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Dermatol, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Burns, JA (reprint author), Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, 1 Bowdoin Square, 11th Floor, Boston, MA 02114 USA. NR 22 TC 17 Z9 17 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 2007 VL 116 IS 11 BP 853 EP 857 PG 5 WC Otorhinolaryngology SC Otorhinolaryngology GA 237DN UT WOS:000251353400011 PM 18074672 ER PT J AU Regenbogen, SE Greenberg, CC Studdert, DM Lipsitz, SR Zinner, MJ Gawande, AA AF Regenbogen, Scott E. Greenberg, Caprice C. Studdert, David M. Lipsitz, Stuart R. Zinner, Michael J. Gawande, Atul A. TI Patterns of technical error among surgical malpractice claims - An analysis of strategies to prevent injury to surgical patients SO ANNALS OF SURGERY LA English DT Article ID ADVERSE EVENTS; OPERATING-ROOM; HOSPITAL VOLUME; SURGEON VOLUME; UNITED-STATES; RISK-FACTORS; HEALTH-CARE; MORTALITY; SAFETY; OUTCOMES AB Objective: To identify the most prevalent patterns of technical errors in surgery, and evaluate commonly recommended interventions in light of these patterns. Summary Background Data: The majority of surgical adverse events involve technical errors, but little is known about the nature and causes of these events. We examined characteristics of technical errors and common contributing factors among closed surgical malpractice claims. Methods: Surgeon reviewers analyzed 444 randomly sampled surgical malpractice claims from four liability insurers. Among 258 claims in which injuries due to error were detected, 52% (n = 133) involved technical errors. These technical errors were further analyzed with a structured review instrument designed by qualitative content analysis. Results: Forty-nine percent of the technical errors caused permanent disability; an additional 16% resulted in death. Two-thirds (65%) of the technical errors were linked to manual error, 9% to errors in judgment, and 26% to both manual and judgment error. A minority of technical errors involved advanced procedures requiring special training ("index operations"; 16%), surgeons inexperienced with the task (14%), or poorly supervised residents (9%). The majority involved experienced surgeons (73%), and occurred in routine rather than index, operations (4%). Patient-related complexities-including emergencies, difficult or unexpected anatomy, and previous. surgery-contributed to 61% of technical errors, and technology or systems failures contributed to 21%. Conclusions: Most technical errors occur in routine operations with experienced surgeons, under conditions of increased patient complexity or systems failure. Commonly recommended interventions, including restricting high-complexity operations to experienced surgeons, additional training for inexperienced surgeons, and stricter supervision of trainees, are likely to address only a minority of technical errors. Surgical safety research should instead focus on improving decision-making and performance in routine operations for complex patients and circumstances. C1 Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Brigham & Womens Hosp, Ctr Surg & Publ Hlth, Boston, MA 02115 USA. RP Regenbogen, SE (reprint author), Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, 677 Huntington Ave, Boston, MA 02115 USA. EM sregenbogen@partners.org OI Gawande, Atul/0000-0002-1824-9176 FU AHRQ HHS [HS011886-03, T32-HS000020] NR 60 TC 78 Z9 86 U1 0 U2 5 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 2007 VL 246 IS 5 BP 705 EP 711 DI 10.1097/SLA.0b013e31815865f8 PG 7 WC Surgery SC Surgery GA 229AJ UT WOS:000250773400003 PM 17968158 ER PT J AU Gold, JS Tang, LH Gonen, M Coit, DG Brennan, MF Allen, PJ AF Gold, Jason S. Tang, Laura H. Gonen, Mithat Coit, Daniel G. Brennan, Murray F. Allen, Peter J. TI Utility of a prognostic nomogram designed for gastric cancer in predicting outcome of patients with R0 resected duodenal adenocarcinoma SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article DE duodenal cancer; gastric cancer; nomogram; survival; prognosis; surgery ID DISEASE-SPECIFIC SURVIVAL; VALIDATION; CARCINOMA AB Background: There is little information to determine prognosis or to guide clinical care for patients with duodenal adenocarcinoma. We have hypothesized that survival following resection of duodenal cancer is similar to survival following resection of distal gastric cancer. We tested the utility of a nomogram created for determining disease-specific survival (DSS) after R0 resection of gastric cancer in estimating DSS for patients with resected duodenal cancer. Methods: Review of a prospective database identified 106 patients who underwent R0 resection of duodenal cancer. Comparison was made to 459 patients with distal gastric cancer. The Student t test, Fisher exact test, Pearson chi-square test, and log-rank test were used to assess statistical significance. Concordance probabilities and calibration plots were used for nomogram validation. Results: Duodenal cancers were more deeply invasive than gastric cancer (P < .01). The rate of lymph node positivity was not statistically different between the two tumors; however, there were differences in the rate of nodal positivity for certain depths of penetration. Younger age (P = .002), negative regional lymph nodes (P = .03), and tumors confined to the bowel wall or subserosa (P = .03) were associated with improved DSS for duodenal cancer. When applied to patients with duodenal cancer, the nomogram had a concordance probability of 0.70, and calibration appeared to be accurate. Conclusions: A nomogram created for determining DSS after resection of gastric cancer predicts outcome for duodenal cancer patients and may prove to be useful for research and in guiding clinical care. C1 Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA. Brigham & Womens Hosp, VA Boston Healthcare Syst, Dept Surg, W Roxbury, MA USA. RP Allen, PJ (reprint author), Mem Sloan Kettering Canc Ctr, Dept Surg, 1275 York Ave, New York, NY 10021 USA. EM allenp@mskcc.org RI Gonen, Mithat/E-4826-2012; Gold, Jason/O-5112-2014; OI Gold, Jason/0000-0002-2925-4755; Brennan, Murray/0000-0003-2358-4371 NR 21 TC 9 Z9 9 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD NOV PY 2007 VL 14 IS 11 BP 3159 EP 3167 DI 10.1245/s10434-007-9542-1 PG 9 WC Oncology; Surgery SC Oncology; Surgery GA 221CH UT WOS:000250204500019 PM 17680313 ER PT J AU McInerney, PA Nicholas, PK Wantland, D Corless, IB Ncama, B Bhengu, B McGibbon, CA Davis, SM Gallagher, DM AF McInerney, Patricia A. Nicholas, Patrice K. Wantland, Dean Corless, Inge B. Ncama, Busisiwe Bhengu, Busisiwe McGibbon, Chris A. Davis, Sheila M. Gallagher, Donna M. TI Characteristics of anti-tuberculosis medication adherence in South Africa SO APPLIED NURSING RESEARCH LA English DT Article ID TUBERCULOSIS; THERAPY AB Adherence to anti-tuberculosis (TB) medications is a critical issue in limiting the spread of the disease throughout the world. In South Africa, medications to treat TB are available at no cost. The purpose of this study was to examine the characteristics of medication adherence in a sample of patients diagnosed with TB (N = 159). The relationships among sociodemographic variables, social support, quality of life, and adherence were explored in this cross-sectional and descriptive study. Self-report data were obtained from a community-based sample of TB-infected individuals who received care in outpatient clinics in Durban, South Africa. Data were collected from the 159 Zulu-and/or English-speaking respondents who agreed to participate in the study. Logistic regression analyses indicated that 41% of the variance in adherence was explained by the model, with nonadherent participants more likely to have less frequent symptoms and more available nutrition than their adherent counterparts. The adherent group was more likely to have increased symptoms, more days with nothing to cat, and fewer appointments with their health care provider. Implications for clinical practice and research are discussed. (C) 2007 Elsevier Inc. All rights reserved. C1 Brigham & Womens Hosp, Div Social Med & Hlth Inequal, Boston, MA 02120 USA. Ctr Nursing Excellence, Boston, MA 02120 USA. MGH Inst Hlth Profess, Boston, MA 02129 USA. Univ KwaZulu Natal, ZA-4004 Durban, South Africa. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ New Brunswick, Fredericton, NB E38 5A3, Canada. Massachusetts Gen Hosp, Boston, MA 02114 USA. New England AIDS Educ & Training, Boston, MA USA. RP Nicholas, PK (reprint author), Brigham & Womens Hosp, Div Social Med & Hlth Inequal, Boston, MA 02120 USA. EM pnicholas@mghihp.edu OI Corless, Inge/0000-0003-0438-2037 NR 17 TC 8 Z9 8 U1 2 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 0897-1897 J9 APPL NURS RES JI Appl. Nurs. Res. PD NOV PY 2007 VL 20 IS 4 BP 164 EP 170 DI 10.1016/j.apnr.2006.06.006 PG 7 WC Nursing SC Nursing GA 233OR UT WOS:000251100700002 PM 17996802 ER PT J AU Fukuoka, Y Rankin, SH Carroll, DL AF Fukuoka, Yoshimi Rankin, Sally H. Carroll, Diane L. TI Systematic bias in self-reported annual household incomes among unpartnered elderly cardiac patients SO APPLIED NURSING RESEARCH LA English DT Article ID ITEM NONRESPONSE; SOCIAL-STATUS; ASSOCIATION; EVENTS; WOMEN; LIFE AB The purpose of this exploratory study was to examine whether specific patient characteristics were associated with not reporting individual incomes among elderly unpartnered cardiac patients. Two hundred forty-seven unpartnered patients (age, >= 65 years) who were admitted with coronary artery disease to one of five university medical centers were interviewed during their hospitalization. Their average age was 76 years (SD = 6.3 years, range = 65-101 years). Of the sample, approximately 34% were men, 92% were Caucasian, 19% had less than 12 years of education, and 55% had at least 12 years (but not more than 16 years) of education. Approximately 13% of the patients did not report their annual household income. In a logistic regression analysis, higher education and greater social and economic satisfaction were significantly related to refusal to self-report income after controlling for age and sex (p < .05). The interaction between education and sex was not significant in the model (p > .05). Our findings indicate that there was a potential systematic bias regarding self-reporting of annual household income. Thus, this systematic bias needs to be examined before performing a multivariate analysis that includes income as a covariate. (C) 2007 Elsevier Inc. All rights reserved. C1 Univ Calif San Francisco, Dept Psychol Nursing, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Family Hlth Care Nursing, San Francisco, CA 94143 USA. Massachusetts Gen Hosp, Yvonne L Munn Ctr Nursing Res, Boston, MA 02114 USA. RP Fukuoka, Y (reprint author), Univ Calif San Francisco, Dept Psychol Nursing, San Francisco, CA 94143 USA. EM yoshimi.fukuoka@nursing.ucsf.edu; sally.rankin@nursing.ucsf.edu; dcarroll3@partners.org FU NICHD NIH HHS [9K12 HD052163-06]; NINR NIH HHS [T32 NR07088, R01 NR005205] NR 18 TC 3 Z9 3 U1 0 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 0897-1897 J9 APPL NURS RES JI Appl. Nurs. Res. PD NOV PY 2007 VL 20 IS 4 BP 205 EP 209 DI 10.1016/j.apnr.2007.01.010 PG 5 WC Nursing SC Nursing GA 233OR UT WOS:000251100700008 PM 17996808 ER PT J AU Greenwood, TA Braff, DL Light, GA Cadenhead, KS Calkins, ME Dobie, DJ Freedman, R Green, MF Gur, RE Gur, RC Mintz, J Nuechterlein, KH Olincy, A Radant, AD Seidman, LJ Siever, LJ Silverman, JM Stone, WS Swerdlow, NR Tsuang, DW Tsuang, MT Turetsky, BI Schork, NJ AF Greenwood, Tiffany A. Braff, David L. Light, Gregory A. Cadenhead, Kristin S. Calkins, Monica E. Dobie, Dorcas J. Freedman, Robert Green, Michael F. Gur, Raquel E. Gur, Ruben C. Mintz, Jim Nuechterlein, Keith H. Olincy, Ann Radant, Allen D. Seidman, Larry J. Siever, Larry J. Silverman, Jeremy M. Stone, William S. Swerdlow, Neal R. Tsuang, Debby W. Tsuang, Ming T. Turetsky, Bruce I. Schork, Nicholas J. TI Initial heritability analyses of endophenotypic measures for schizophrenia - The consortium on the genetics of schizophrenia SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID VARIANCE-COMPONENTS MODELS; AUDITORY-EVOKED-RESPONSES; QUANTITATIVE-TRAIT LOCI; WORKING-MEMORY; ANTISACCADE PERFORMANCE; BIOLOGICAL RELATIVES; SUSTAINED ATTENTION; PREPULSE INHIBITION; P50 SUPPRESSION; NEUROCOGNITIVE ENDOPHENOTYPES AB Context: Exploration of the genetic architecture of specific endophenotypes may be a powerful strategy for understanding the genetic basis of schizophrenia. Objective: To characterize the genetic architecture of some key endophenotypic measures selected for their reported heritabilities in schizophrenia. Design: Family-based heritability study. Setting: Seven sites across the United States. Participants: At the time of these initial data analyses, the members of 183 nuclear families ascertained through probands with schizophrenia had been assessed for these endophenotypes. Main Outcome Measures: Variance component models were used to assess the heritability of and the environmental and genetic correlations among the endophenotypes. The Consortium on the Genetics of Schizophrenia assesses the neurophysiologic measures of prepulse inhibition of acoustic startle, P50 event-related potential suppression, and the antisaccade task for eye movements and the neurocognitive measures of the Continuous Performance Test (Degraded Stimulus version), the California Verbal Learning Test, the Letter-Number Sequencing test, and 6 measures from the University of Pennsylvania Computerized Neurocognitive Battery. The heritabilities of these 12 measures are the focus of this article. Results: All of the endophenotypes and the University of Pennsylvania Computerized Neurocognitive Battery measures were found to be significantly heritable (P <=. 005), with heritabilities ranging from 24% to 55%. Significant environmental and genetic correlations were also observed between many of the endophenotypic measures. Conclusion: This is the first large-scale, multisite, family-based heritability study of a collection of endophenotypes for schizophrenia and suggests that endophenotypes are important measures to consider in characterizing the genetic basis of schizophrenia. C1 Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. Univ Calif San Diego, Ctr Human Genet & Genom, La Jolla, CA 92093 USA. Univ Calif San Diego, Dept Biostat, La Jolla, CA 92093 USA. Univ Penn, Dept Psychiat, Philadelphia, PA 19104 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Colorado, Hlth Sci Ctr, Dept Psychiat, Denver, CO 80262 USA. Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, Geffen Sch Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Neuropsychiat Inst Biostat Core, Los Angeles, CA 90024 USA. Beth Israel Deaconess Med Ctr, Publ Psychiat Div, Massachusetts Mental Hlth Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Harvard Inst Psychiat Epidemiol & Genet, Boston, MA USA. CUNY Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. James J Peters VA Med Ctr, New York, NY USA. Educ Clin Ctr, Vet Integrated Serv Network Mental Illness Res 3, New York, NY USA. RP Schork, NJ (reprint author), Scripps Hlth & Scripps Res Inst, 10550 N Torrey Pines Rd, La Jolla, CA 92037 USA. EM nschork@scripps.edu RI Greenwood, Tiffany/F-6356-2012; Tsuang, Debby/L-7234-2016; Mintz, Jim/N-7385-2014 OI Greenwood, Tiffany/0000-0002-6080-6503; Tsuang, Debby/0000-0002-4716-1894; Mintz, Jim/0000-0002-8299-5851 FU NIMH NIH HHS [R01 MH65578, R01 MH42228, R01 MH65554, R01 MH65558, R01 MH65562, R01 MH65571, R01 MH65588, R01 MH65707] NR 83 TC 230 Z9 237 U1 2 U2 12 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD NOV PY 2007 VL 64 IS 11 BP 1242 EP 1250 DI 10.1001/archpsyc.64.11.1242 PG 9 WC Psychiatry SC Psychiatry GA 228BK UT WOS:000250701700003 PM 17984393 ER PT J AU Chao, LL Schuff, N Clevenger, EM Mueller, SG Rosen, HJ Gorno-Tempini, ML Kramer, JH Miller, BL Weiner, MW AF Chao, Linda L. Schuff, Norbert Clevenger, Erin M. Mueller, Susanne G. Rosen, Howard J. Gorno-Tempini, Maria L. Kramer, Joel H. Miller, Bruce L. Weiner, Michael W. TI Patterns of white matter atrophy in frontotemporal lobar degeneration SO ARCHIVES OF NEUROLOGY LA English DT Article ID RHESUS-MONKEY; SEMANTIC DEMENTIA; ALZHEIMERS-DISEASE; BRAIN ATROPHY; MR-IMAGES; CORTICAL AFFERENTS; CORTEX; SEGMENTATION; CONNECTIONS; MORPHOMETRY AB Background: Structural magnetic resonance imaging (MRI) has been used to investigate the in vivo pathology of frontotemporal lobar degeneration. However, few neuroimaging studies have focused on white matter(WM) alterations in this disease. Objectives: To use volumetric MRI techniques to identify the patterns of WM atrophy in vivo in 2 clinical variants of frontotemporal lobar degeneration - frontotemporal dementia (FTD) and semantic dementia - and to compare the patterns of WM atrophy with those of gray matter ( GM) atrophy in these diseases. Design: Structural MRIs were obtained from patients with FTD (n = 12) and semantic dementia (n = 13) and in cognitively healthy age-matched controls (n= 24). Regional GM and WM were classified automatically from high-resolution T1-, T2-, and proton density-weighted MRIs with Expectation-Maximization Segmentation and compared between the groups using a multivariate analysis of covariance model that included age and WM lesion volumes as covariates. Results: Patients with FTD had frontal WM atrophy and frontal, parietal, and temporal GM atrophy compared with controls, who had none. Patients with semantic dementia had temporal WM and GM atrophy and patients with FTD had frontal GM atrophy. Adding temporal WM volume to temporal GM volume significantly improved the discrimination between semantic dementia and FTD. Conclusions: These results show that patients with frontotemporal lobar degeneration who are in relatively early stages of the disease (Clinical Dementia Rating score, 1.0-1.2) have WM atrophy that largely parallels the pattern of GM atrophy typically associated with these disorders. C1 Univ Calif San Francisco, Dept Vet Affairs Med Ctr, Dept Radiol, San Francisco, CA 94121 USA. Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. San Francisco VA Med Ctr, Ctr Imaging Neurodegenerat Dis, San Francisco, CA USA. RP Chao, LL (reprint author), Univ Calif San Francisco, Dept Vet Affairs Med Ctr, Dept Radiol, 4150 Clement St 114M, San Francisco, CA 94121 USA. EM linda.chao@ucsf.edu RI Gorno-Tempini, Maria Luisa/E-7203-2012 FU NIA NIH HHS [P01 AG019724, P01 AG19724, P01 AG019724-050002] NR 39 TC 16 Z9 17 U1 0 U2 3 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 2007 VL 64 IS 11 BP 1619 EP 1624 DI 10.1001/archneur.64.11.1619 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 229YZ UT WOS:000250843800008 PM 17998444 ER PT J AU Olson, JD Brandt, JT Chandler, WL Van Cott, EM Cunningham, MT Hayes, TE Kottke-Marchant, KK Makar, RS Uy, AB Wang, EC AF Olson, John D. Brandt, John T. Chandler, Wayne L. Van Cott, Elizabeth M. Cunningham, Mark T. Hayes, Timothy E. Kottke-Marchant, Kandice K. Makar, Robert S. Uy, Arby B. Wang, Edward C. TI Laboratory reporting of the international normalized ratio - Progress and problems SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article ID PROTHROMBIN TIME; THROMBOPLASTIN; CALIBRATION AB Context. - The international normalized ratio ( INR) is widely used to monitor oral anticoagulation and to evaluate patients with coagulation disorders. Objective. - To examine the variability of the performance and reporting of the INR and to evaluate laboratory calculation of the INR. Design. - Between 1993 and 2003, laboratories participating in proficiency testing were surveyed. Participants provided the international sensitivity index and the mean normal prothrombin time used to calculate the INR. The INR was calculated from the data provided and compared with the INR reported to determine if the calculation was correct. Results. - Survey data regarding the INR collected between 1993 and 2003 demonstrate an improvement in reporting, using appropriate anticoagulant, using lower international sensitivity index reagents, and matching international sensitivity index and prothrombin time method. The all- method coefficient of variation of the INR improved from 18% to 5.8%. Among 3813 laboratories studied in 2002 and 2003, 4.1% miscalculated INR. Of 29 laboratories that reported investigation of the INR miscalculation, 11 ( 38%) reported correcting an INR that was being reported in patient results and that this error was corrected as a result of the study. Since beginning grading of the INR calculation, miscalculation of the INR has fallen to less than 1%. Conclusions. - Recommendations for change in laboratory practice made by consensus conferences are implemented during the course of many years. Difficulty calculating the INR was documented, and both the calculation and the variability in the reporting of the INR showed improvement. Proficiency testing, when closely evaluated and acted on, can have a direct impact on the quality of patient care. C1 Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78229 USA. Eli Lilly & Co, Lilly Corp Ctr, Indianapolis, IN 46285 USA. Univ Washington, Lab Med, Seattle, WA 98195 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Univ Kansas, Med Ctr, Dept Pathol, Kansas City, KS 66045 USA. Maine Med Ctr, Dept Pathol, Portland, ME USA. Cleveland Clin, Dept Clin Pathol, Cleveland, OH 44106 USA. Coll Amer Pathologists, Northfield, IL USA. Univ Illinois, Coll Nursing, Chicago, IL USA. RP Olson, JD (reprint author), Univ Texas, Hlth Sci Ctr, Dept Pathol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM olsonj@uthscsa.edu NR 11 TC 13 Z9 13 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 2007 VL 131 IS 11 BP 1641 EP 1647 PG 7 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 228MS UT WOS:000250734600008 PM 17979481 ER PT J AU Chaudhry, IH Zembowicz, A AF Chaudhry, Iskander H. Zembowicz, Artur TI Adnexal clear cell carcinoma with comedonecrosis - Clinicopathologic analysis of 12 cases SO ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE LA English DT Article; Proceedings Paper CT 95th Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY FEB 11-17, 2006 CL Atlanta, GA SP US & Canadian Acad Pathol ID MALIGNANT ECCRINE POROMA; SQUAMOUS-CELL; BASAL-CELL; TRICHOLEMMAL CARCINOMA; SEBACEOUS DIFFERENTIATION; SKIN; NEOPLASMS; METASTASIS; MELANOMA; VARIANT AB Context. - Cutaneous clear cell tumors can pose a diagnostic challenge even to the experienced dermatopathologist; this is partly because of limitations of existing diagnostic categories. Objective. - To describe a previously unrecognized, distinctive cutaneous adnexal carcinoma capable of an aggressive clinical course. Design. - Clinicopathologic analysis of a series of 12 cases. Results. - The patients were older individuals ( median age, 71 years) with equal gender frequency. The lesions showed wide anatomic distribution with predilection for the head and neck area, especially the scalp. The lesions presented as rapidly growing, erythematous to flesh-colored, solitary papules/nodules that were capable of quickly reaching a size of several centimeters. Histologically, adnexal clear cell carcinoma with comedonecrosis was characterized by dermal proliferation of nests of epithelial cells showing distinctive zonal arrangement. The periphery of the tumor nests was formed by squamoid cells merging with centrally located clear cell areas containing foci of comedonecrosis. The lesions often showed multilobular or trabecular growth pattern and infiltrating border. Nuclear pleomorphism was variable; mitotic count ranged from 2 to 32/mm(2) ( median, 8/mm(2)). No ductal, cuticular, or apocrine differentiation was seen. All cases showed expression of epithelial membrane antigen and cytokeratin 17 in clear cells, with focal carcinoembryonic antigen expression in some cases. Follow-up ( average, 37 months) revealed local recurrence ( 4 cases) and regional and distant metastases ( 2 cases). Conclusions. - Adnexal clear cell carcinoma with comedonecrosis appears to be a distinctive adnexal neoplasm that has to be distinguished from more indolent squamous cell and tricholemmal carcinomas. C1 Massachusetts Gen Hosp, Harvard Univ, Sch Med, Dermatopathol Unit, Boston, MA 02115 USA. Leeds Gen Infirmary, Dept Pathol, Leeds, W Yorkshire, England. RP Zembowicz, A (reprint author), Massachusetts Gen Hosp, Harvard Univ, Sch Med, Dermatopathol Unit, Boston, MA 02115 USA. EM dr.Zembowicz@gmail.com NR 35 TC 5 Z9 5 U1 0 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 2007 VL 131 IS 11 BP 1655 EP 1664 PG 10 WC Medical Laboratory Technology; Medicine, Research & Experimental; Pathology SC Medical Laboratory Technology; Research & Experimental Medicine; Pathology GA 228MS UT WOS:000250734600010 PM 17979483 ER PT J AU Turner, AP Kivlahan, DR Kazis, LE Haselkorn, JK AF Turner, Aaron P. Kivlahan, Daniel R. Kazis, Lewis E. Haselkorn, Jodie K. TI Smoking among veterans with multiple sclerosis: Prevalence correlates, quit attempts, and unmet need for services SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article; Proceedings Paper CT Consortium of Multiple Sclerosis 2006 CY JUN 01-03, 2006 CL Scottsdale, AZ DE mental health; multiple sclerosis; pain; rehabilitation; smoking; smoking cessation ID CIGARETTE-SMOKING; ORAL-CONTRACEPTIVES; BACK-PAIN; CESSATION; DEPRESSION; RISK; ANXIETY; PHYSICIANS; INITIATION; NICOTINE AB Turner AP, Kivlahan DR, Kazis LE, Haselkorn JK. Smoking among veterans with multiple sclerosis: prevalence, correlates, quit attempts, and unmet need for services. Arch Phys Med Rehabil 2007;88:1394-9. Objective: To describe the prevalence and correlates of smoking as well as quit attempts and unmet need for smoking cessation services in a national sample of veterans with multiple sclerosis (MS). Design: Cross-sectional cohort study linking computerized medical record information to mailed survey data from 1999. Setting: Veterans Health Administration (VHA). Participants: Sixty-four percent (2994/4685) of veterans with MS who received services in VHA and also returned survey questionnaires, as well as a 20% random subsample (n=569) who completed a more extensive assessment of smoking. Interventions: Not applicable. Main Outcome Measures: Items assessing smoking, quit attempts, and unmet need for smoking services. Results: Among all survey respondents with MS, 28.5% (95% confidence interval [CI], 26.9-30.2) endorsed current smoking. Of extended survey respondents, 54.5% (95% CI, 46.6 - 62. 1) reported a quit attempt in the past year, and 59.0% (95% CI, 51.1-66.4) reported not getting needed services for smoking in the past year. In fully adjusted logistic regression, smoking was associated with younger age, lower levels of education, being unmarried, higher levels of physical pain, and poorer mental health. A quit attempt was associated with higher levels of education and greater pain intensity. Conclusions: Smoking among veterans with NIS is common, with rates similar to those for other veterans. There is substantial need for cessation services. Cessation interventions should address correlates of smoking including pain, poorer mental health, and social isolation. C1 VA Puget Sound Hlth Care Syst, Rehabil Care Serv, Seattle, WA 98108 USA. VA MS Ctr Excellence W, Seattle, WA USA. VA Ctr Excellence Substance Abuse Treatment & Edu, Seattle, WA USA. Boston Univ, Dept Publ Hlth, Boston, MA 02215 USA. Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. VA ctr Hlth Qual Outcomes & Econ Res, Boston, MA USA. RP Turner, AP (reprint author), VA Puget Sound Hlth Care Syst, Rehabil Care Serv, S-117-RCS,1660 S Columbian Way, Seattle, WA 98108 USA. EM Aaron.Turner@va.gov OI Turner, Aaron/0000-0001-6897-8003 NR 61 TC 11 Z9 11 U1 1 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD NOV PY 2007 VL 88 IS 11 BP 1394 EP 1399 DI 10.1016/j.apinr.2007.08.003 PG 6 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 229AT UT WOS:000250774400004 PM 17964878 ER PT J AU Monga, U Garber, SL Thornby, J Vallbona, C Kerrigan, AJ Monga, TN Zimmermann, KP AF Monga, Uma Garber, Susan L. Thornby, John Vallbona, Carlos Kerrigan, Anthony J. Monga, Trilok N. Zimmermann, Kuno P. TI Exercise prevents fatigue and improves quality of life in prostate cancer patients undergoing radiotherapy SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE exercise; prostate cancer; quality of life; rehabilitation ID BECK DEPRESSION INVENTORY; BREAST-CANCER; FUNCTIONAL ASSESSMENT; THERAPY; SURVIVORS; OUTCOMES; WOMEN; REHABILITATION; VALIDATION; RADIATION AB Monga U, Garber SL, Thornby J, Vallbona C, Kerrigan AJ, Monga TN, Zimmermann KP. Exercise prevents fatigue and improves quality of life in prostate cancer patients undergoing radiotherapy. Arch Phys Med Rehabil 2007;88: 1416-22. Objective: To show fatigue prevention and quality of life (QOL) improvement from cardiovascular exercise during radiotherapy. Design: Prospective enrollment (n=21), randomized to exercise (n =11) and control groups (n =10), with pre- and post-radiotherapy between- and within-group comparisons. Setting: Academic medical center. Participants: Localized prostate cancer patients undergoing radiotherapy. Interventions: The interventional group received radiotherapy plus aerobic exercise 3 times a week for 8 weeks whereas the control group received radiotherapy without exercise. Main Outcome Measures: Pre- and post-radiotherapy differences in cardiac fitness, fatigue, depression, functional status, physical, social, and functional well-being, leg strength, and flexibility were examined within and between 2 groups. Results: No significant differences existed between 2 groups at pre-radiotherapy assessment. At post-radiotherapy assessment, the exercise group showed significant within group improvements in: cardiac fitness (P<001), fatigue (P=.02), Functional Assessment of Cancer Therapy-Prostate (FACT-P) (P=.04), physical well-being (P=.002), social well-being (P=.02), flexibility (P=.006), and lea strength (P=.000). Within the control group, there was a significant increase in fatigue score (P=.004) and a decline in social well-being (P<05) at post-radiotherapy assessment. Between-group differences at post-radiotherapy assessment were significant in cardiac fitness (P=.006), strength (P=.000), flexibility (P<01), fatigue (P<001), FACT-P (P=.006), physical wellbeing (P<001), social well-being (P=.002), and functional well-being (P=.04). Conclusions: An 8-week cardiovascular exercise program in patients with localized prostate cancer undergoing radiotherapy improved cardiovascular fitness, flexibility, muscle strength., and overall QOL and prevented fatigue. C1 Michael E DeBakey Dept Vet Affairs Med Ctr, Rehabil Care Line 117, Houston, TX 77030 USA. Baylor Coll Med, Dept Radiol, Houston, TX 77030 USA. Baylor Coll Med, Dept Phys Med & Rehabil, Houston, TX 77030 USA. Baylor Coll Med, Dept Family & Community Med, Houston, TX 77030 USA. Michael E DeBakey Dept Vet Affairs Med Ctr, Diagnost & Therapeut Care Line, Houston, TX USA. Michael E DeBakey Dept Vet Affairs Med Ctr, Res Care Line, Houston, TX USA. Michael E DeBakey Dept Vet Affairs Med Ctr, Rehabil Care Line, Houston, TX USA. Michael E DeBakey Dept Vet Affairs Med Ctr, Mental Hlth Care Line, Houston, TX USA. RP Zimmermann, KP (reprint author), Michael E DeBakey Dept Vet Affairs Med Ctr, Rehabil Care Line 117, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM zimmermann.kunop@med.va.gov NR 48 TC 71 Z9 72 U1 6 U2 18 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD NOV PY 2007 VL 88 IS 11 BP 1416 EP 1422 DI 10.1016/j.apmr.2007.08.110 PG 7 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 229AT UT WOS:000250774400007 PM 17964881 ER PT J AU Utz, A Biller, BMK AF Utz, Andrea Biller, Beverly M. K. TI The role of bilateral lnferior petrosal sinus sampling in the diagnosis of Cushing's syndrome SO ARQUIVOS BRASILEIROS DE ENDOCRINOLOGIA E METABOLOGIA LA English DT Article DE IPSS; BIPSS; Cushing's; ectopic; pituitary; bilateral inferior petrosal sinus sampling ID CORTICOTROPIN-RELEASING HORMONE; ECTOPIC ADRENOCORTICOTROPIN SYNDROME; INFERIOR PETROSAL; DIFFERENTIAL-DIAGNOSIS; NEUROLOGICAL COMPLICATION; DISEASE; STATES; ACTH; THROMBOEMBOLISM; DESMOPRESSIN AB Adrenocorticotropin hormone (ACTH)-dependent Cushing's syndrome is most often due to a pituitary corticotroph adenoma, with ectopic ACTH-secreting tumors representing approximately 15% of cases. Biochemical and radiological techniques have been established to help distinguish between these two entities, and thus aid in the localization of the neoplastic lesion for surgical resection. The test that offers the highest sensitivity and specificity is bilateral inferior petrosal sinus sampling (BIPSS). BIPSS is an interventional radiology procedure in which ACTH levels obtained from venous drainage very near the pituitary gland are compared to peripheral blood levels before and after corticotropin hormone (CRH) stimulation. A gradient between these two locations indicates pituitary Cushing's, whereas the absence of a gradient suggests ectopic Cushing's. Accurate BIPSS results require hypercortisolemia to suppress normal corticotroph ACTH production and hypercortisolemia at the time of the BIPSS to assure excessive ACTH secretion. In some cases, intrapituitary gradients from side-to-side can be helpful to localize small corticotroph adenomas within the sella. BIPSS has rare complications and is considered safe when performed at centers with experience in this specialized technique. C1 [Utz, Andrea; Biller, Beverly M. K.] Massachusetts Gen Hosp, Neuroendocrine Unit, Boston, MA 02114 USA. RP Biller, BMK (reprint author), Massachusetts Gen Hosp, Neuroendocrine Unit, Bulfinch 457,55 Fruit St, Boston, MA 02114 USA. EM bbiller@partners.org NR 37 TC 12 Z9 20 U1 0 U2 1 PU SBEM-SOC BRASIL ENDOCRINOLOGIA & METABOLOGIA PI RIO DE JANEIRO, RJ PA RUA HUMAITA, 85 CJ 501, RIO DE JANEIRO, RJ, 22261-000, BRAZIL SN 0004-2730 EI 1677-9487 J9 ARQ BRAS ENDOCRINOL JI Arq. Bras. Endocrinol. Metabol. PD NOV PY 2007 VL 51 IS 8 BP 1329 EP 1338 DI 10.1590/S0004-27302007000800019 PG 10 GA 307UP UT WOS:000256344300019 PM 18209871 ER PT J AU Costouros, JG Porramatikul, M Lie, DT Warner, JJP AF Costouros, John G. Porramatikul, Mason Lie, Denny T. Warner, Jon J. P. TI Reversal of suprascapular neuropathy following arthroscopic repair of massive supraspinatus and infraspinatus rotator cuff tears SO ARTHROSCOPY-THE JOURNAL OF ARTHROSCOPIC AND RELATED SURGERY LA English DT Article DE Arthroscopy; neuropathy; rotator cuff; shoulder; suprascapular ID ENTRAPMENT NEUROPATHY; NERVE ENTRAPMENT; NOTCH; INJURY; DEGENERATION; CONVERGENCE; ASSOCIATION; INTEGRITY; DIAGNOSIS; SHOULDER AB Purpose: The purpose of this study was to study the prevalence of suprascapular neuropathy (SSN) in the setting of massive rotator cuff tears and to determine if arthroscopic rotator cuff repair, even if partial, was associated with reversal of SSN and clinical improvement in pain and function. Methods: Over a 13-month period, 26 of 216 patients with rotator cuff tears treated operatively were identified to have massive tears associated with retraction and moderate to severe fatty infiltration of the supraspinatus and infraspinatus muscles. All patients had pain and marked weakness in abduction and external rotation which did not improve with conservative treatment. Electrodiagnostic electromyographic/nerve conduction velocity (EMG/NCV) evaluation, as well as pre- and postoperative questionnaire and physical examination, were performed. An arthroscopic repair, either partial or complete, was performed on patients identified to have a massive rotator cuff tear in association with SSN. Results: Fourteen of 26 patients with massive rotator cuff tears (54%) were identified to have a peripheral nerve injury. Seven of these 26 (38%) had isolated suprascapular nerve injury, 4 had axillary nerve injury, 2 had an associated upper trunk brachial plexus injury, and 1 had a cervical radiculopathy. All 7 patients with isolated suprascapular injury underwent arthroscopic treatment, 1 of which was not technically reparable at the time of surgery. In the 6 patients who underwent either partial or complete arthroscopic repair, follow-up EMG/NCV after 6 months demonstrated partial or full recovery of the suprascapular nerve palsy that correlated with complete pain relief and marked improvement in function. Conclusions: SSN is found in a significant proportion of patients with massive rotator cuff tears, and is associated with pain and dysfunction. Arthroscopic rotator cuff repair can result in reversal of SSN, which may correlate with substantial improvement in pain and function. C1 Massachusetts Gen Hosp, Yawkey Ctr Outpatient Care, Dept Orthopaed Surg, Harvard Shoulder Serv, Boston, MA 02114 USA. RP Warner, JJP (reprint author), Massachusetts Gen Hosp, Yawkey Ctr Outpatient Care, Dept Orthopaed Surg, Harvard Shoulder Serv, 55 Fruit St,Suite 3200, Boston, MA 02114 USA. EM jwarner@partners.org NR 43 TC 73 Z9 74 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 0749-8063 J9 ARTHROSCOPY JI Arthroscopy PD NOV PY 2007 VL 23 IS 11 BP 1152 EP 1161 DI 10.1016/j.arthro.2007.06014 PG 10 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 234FJ UT WOS:000251145800003 PM 17986401 ER PT J AU Neale, BM Daly, MJ Asherson, P McGuffin, P Neale, MC AF Neale, Benjamin M. Daly, Mark J. Asherson, Philip McGuffin, Peter Neale, Michael C. TI Considerations for association analysis of multiple correlated traits and samples SO BEHAVIOR GENETICS LA English DT Meeting Abstract CT 37th Annual Meeting of the Behavior-Genetics-Association CY JUN 03-08, 2007 CL Amsterdam, NETHERLANDS SP Behav Genet Assoc C1 [Neale, Benjamin M.; Asherson, Philip; McGuffin, Peter] Kings Coll London, Inst Psychiat, Social Genet & Dev Psychiat Ctr, London, England. [Neale, Benjamin M.; Daly, Mark J.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Neale, Benjamin M.; Daly, Mark J.] MIT, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02139 USA. [Daly, Mark J.] Harvard Med Sch, Boston, MA USA. [Neale, Michael C.] Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Richmond, VA 23284 USA. [Neale, Michael C.] Virginia Commonwealth Univ, Dept Psychiat, Dept Human Genet, Dept Psychol, Richmond, VA 23284 USA. [Neale, Michael C.] Free Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands. EM b.neale@iop.kcl.ac.uk RI Neale, Michael/B-1418-2008; McGuffin, Peter/A-1565-2012 OI McGuffin, Peter/0000-0002-9888-2907 NR 0 TC 0 Z9 0 U1 0 U2 0 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 2007 VL 37 IS 6 BP 778 EP 779 PG 2 WC Behavioral Sciences; Genetics & Heredity; Psychology, Multidisciplinary SC Behavioral Sciences; Genetics & Heredity; Psychology GA 231VK UT WOS:000250977100111 ER PT J AU Flessner, CA Woods, DW Franklin, ME Keuthen, NJ Piacentini, J Cashin, SE Moore, PS AF Flessner, Christopher A. Woods, Douglas W. Franklin, Martin E. Keuthen, Nancy J. Piacentini, John Cashin, Susan E. Moore, Phoebe S. TI The Milwaukee inventory for styles of trichotillomania-child version (MIST-C) - Initial development and psychometric properties SO BEHAVIOR MODIFICATION LA English DT Article DE focused; automatic; pulling; trichotillomania ID DEPRESSION INVENTORY; CONCURRENT VALIDITY; BEHAVIORAL-THERAPY; ECONOMIC-IMPACT; HABIT-REVERSAL; SKIN-PICKING; HAIR PULLERS; COMORBIDITY; RELIABILITY; DISORDERS AB This article describes the development and initial psychometric properties of the Milwaukee Inventory for Styles of Trichotillomania-Child Version (MIST-Q, a self-report scale designed to assess styles of hair pulling in children and adolescents diagnosed with trichotillomania (TTM). Using Internet sampling procedures, the authors recruited 164 parent-child dyads, the children of whom met modified diagnostic criteria for TTM. The MIST-C was administered in the context of a larger survey examining functional impairment experienced by children with TTM. Results of an exploratory factor analysis on MIST-C items revealed a two-factor solution. Factors 1 ("focused" pulling scale) and 2 ("automatic" pulling scale) consisted of 21 and 4 items, respectively, with both scales demonstrating acceptable internal consistency and good construct and discriminant validity. The development of the MIST-C provides researchers with a reliable and valid assessment of "automatic" and "focused" pulling, and provides a means by which to examine the developmental trajectory and treatment implications of these pulling styles. C1 Univ Wisconsin, Milwaukee, WI 53201 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Univ Calif Los Angeles, Los Angeles, CA USA. Duke Univ, Med Ctr, Durham, NC USA. RP Flessner, CA (reprint author), Univ Wisconsin, Milwaukee, WI 53201 USA. RI Citations, TLC SAB/C-4006-2011; Flessner, Christopher/K-1483-2015; Piacentini, John/C-4645-2011 NR 45 TC 38 Z9 39 U1 1 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0145-4455 J9 BEHAV MODIF JI Behav. Modificat. PD NOV PY 2007 VL 31 IS 6 BP 896 EP 918 DI 10.1177/0145445507302521 PG 23 WC Psychology, Clinical SC Psychology GA 223NZ UT WOS:000250379100012 PM 17932243 ER PT J AU Strehler, EE Filoteo, AG Penniston, JT Caride, AJ AF Strehler, E. E. Filoteo, A. G. Penniston, J. T. Caride, A. J. TI Plasma-membrane Ca2+ pumps: structural diversity as the basis for functional versatility SO BIOCHEMICAL SOCIETY TRANSACTIONS LA English DT Article; Proceedings Paper CT Focus Topic at Life Sciences 2007 Conference CY JUL 09-12, 2007 CL Glasgow, SCOTLAND DE calcium pump; calcium regulation; calcium signalling; calmodulin; plasma-membrane Ca2+-ATPase (PMCA) ID CALCIUM-PUMP; LIPID RAFTS; ISOFORM 4; CA2+-ATPASE; ATPASE; HOMEOSTASIS; ACTIVATION AB Plasma-membrane calcium pumps [PMCAs (plasma-membrane Ca2+-ATPases)] expel Ca2+ from eukaryotic cells to maintain overall Ca2+ homoeostasis and to provide local control of intracellular Ca2+ signalling. Recent work indicates functional versatility among PMCA isoforms, with specific pumps being essential for cochlear hair cell function, sperm motility, feedback signalling in the heart and pre- and post-synaptic Ca2+ regulation in neurons. The functional versatility of PMCAs is due to differences in their regulation by CaM (calmodulin), kinases and other signalling proteins, as well as to their differential targeting and retention in defined plasma membrane domains. The basis for this is the structural diversity of PMCAs. in mammals, four genes encode PMCA isoforms 1-4, and each of these has multiple variants generated by alternative RNA splicing. The alternatively spliced regions are intimately involved in the regulatory interactions and differential membrane localization of the pumps. The alternatively spliced C-terminal tail acts as an autoinhibitory domain by interacting with the catalytic core of the pump. The degree of inhibition and the kinetics of interaction with the major activator CaM differ between PMCA variants. This translates into functional differences in how PMCAs handle Ca2+ signals of different magnitude and frequency. Accumulating evidence thus demonstrates how structural diversity provides functional versatility in the PMCAs. C1 Mayo Clin, Coll Med, Dept Biochem & Mol Biol, Rochester, MN 55905 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Strehler, EE (reprint author), Mayo Clin, Coll Med, Dept Biochem & Mol Biol, 200 1st St SW, Rochester, MN 55905 USA. EM strehler.emanuel@mayo.edu FU NIGMS NIH HHS [GM28835, R01 GM028835, R01 GM028835-25]; NINDS NIH HHS [R01 NS051769-01A1, NS51769, R01 NS051769] NR 28 TC 57 Z9 58 U1 1 U2 14 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 2007 VL 35 BP 919 EP 922 DI 10.1042/BST0350919 PN 5 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 236CE UT WOS:000251279800018 PM 17956246 ER PT J AU Marshansky, V AF Marshansky, V. TI The V-ATPase a2-subunit as a putative endosomal pH-sensor SO BIOCHEMICAL SOCIETY TRANSACTIONS LA English DT Article; Proceedings Paper CT Focus Topic at Life Sciences 2007 Conference CY JUL 09-12, 2007 CL Glasgow, SCOTLAND DE ADP-ribosylation factor (Art); endosome/lysosome; pH-sensor; protein degradative pathway; vesicular H+-ATPase (V-ATPase) ID VACUOLAR H+-ATPASE; RECEPTOR-MEDIATED ENDOCYTOSIS; NUCLEOTIDE EXCHANGE FACTOR; ADP-RIBOSYLATION FACTOR; PROTON-TRANSLOCATING ATPASE; RENAL TUBULAR-ACIDOSIS; BINDING PROTEIN; DENTS-DISEASE; INTRACELLULAR-TRANSPORT; MOLECULAR-CLONING AB V-ATPase (vesicular H+-ATPase)-driven intravesicular acidification is crucial for vesicular trafficking. Defects in vesicular acidification and trafficking have recently been recognized as essential determinants of various human diseases. An important role of endosomal acidification in receptor-ligand dissociation and in activation of lysosomal hydrolytic enzymes is well established. However, the molecular mechanisms by which luminal pH information is transmitted to the cytosolic small GTPases that control trafficking events such as budding, coat formation and fusion are unknown. Here, we discuss our recent discovery that endosomal V-ATPase is a pH-sensor regulating the degradative pathway. According to our model, V-ATPase is responsible for: (i) the generation of a pH gradient between vesicular membranes; (ii) sensing of intravesicular pH; and (iii) transmitting this information to the cytosolic side of the membrane. We also propose the hypothetical molecular mechanism involved in function of the V-ATPase a2-subunit as a putative pH-sensor. Based on extensive experimental evidence on the crucial role of histidine residues in the function of PSPs (pH-sensing proteins) in eukaryotic cells, we hypothesize that pH-sensitive histidine residues within the intra-endosomal loops and/or C-terminal luminal tail of the a2-subunit could also be involved in the pH-sensing function of V-ATPase. However, in order to identify putative pH-sensitive histidine residues and to test this hypothesis, it is absolutely essential that we increase our understanding of the folding and transmembrane topology of the a-subunit isoforms of V-ATPase. Thus the crucial role of intra-endosomal histidine residues in pH-dependent conformational changes of the V-ATPase a2-isoform, its interaction with cytosolic small GTPases and ultimately in its acidification-dependent regulation of the endosomal/lysosomal protein degradative pathway remain to be determined. C1 Massachusetts Gen Hosp, Program Membrane Biol, Ctr Syst Biol, Richard Simches Res Ctr, Boston, MA 02114 USA. RP Marshansky, V (reprint author), Massachusetts Gen Hosp, Program Membrane Biol, Ctr Syst Biol, Richard Simches Res Ctr, CPZN 8212,185 Cambridge St, Boston, MA 02114 USA. EM viadimir_marshansky@hms.harvard.edu FU NIDDK NIH HHS [DK038452, DK057521-08] NR 76 TC 50 Z9 51 U1 1 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 2007 VL 35 BP 1092 EP 1099 PN 5 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 236CE UT WOS:000251279800059 PM 17956287 ER PT J AU Kitagaki, H Cowart, LA Matmati, N de Avalos, SV Novgorodov, SA Zeidan, YH Bielawski, J Obeid, LM Hannun, YA AF Kitagaki, Hiroshi Cowart, L. Ashley Matmati, Nabil de Avalos, Silvia Vaena Novgorodov, Sergei A. Zeidan, Youssef H. Bielawski, Jacek Obeid, Lina M. Hannun, Yusuf A. TI Isc 1 regulates sphingolipid metabolism in yeast mitochondria SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES LA English DT Article DE mitochondria; sphingolipid; sphingomyelinase; lipidomics; ISC1; yeast ID PHOSPHOSPHINGOLIPID PHOSPHOLIPASE-C; RAT-LIVER MITOCHONDRIA; SACCHAROMYCES-CEREVISIAE; ANIONIC PHOSPHOLIPIDS; ENDOPLASMIC-RETICULUM; ALKALINE CERAMIDASE; LIPID-COMPOSITION; OUTER-MEMBRANE; CONTACT SITES; CELL-SURFACE AB The Saccharomyces cerevisiae inositol sphingolipid phospholipase C (Ise 1 p), a homolog of mammalian neutral sphingomyelinases, hydrolyzes complex sphingolipids to produce ceramide in vitro. Epitope-tagged Ise I p associates with the mitochondria, in the post-diauxic phase of, east growth. In this report, the mitochondrial localization of Isclp and its role in regulating sphingolipid metabolism were investigated. First, endogenous Iscip activity was enriched in highly purified mitochondria, and western blots using highly purified mitochondrial membrane fractions demonstrated that epitope-tagged Isc 1p localized to the outer mitochondrial membrane as an integral membrane protein. Next, LC/MS was employed to determine the sphingolipid composition of highly purified mitochondria which were found to be significantly enriched in alpha-hydroxylated phytoceramides (21.7 fold) relative to the whole cell. Mitochondria, on the other hand, were significantly depleted in sphingoid bases. Compared to the parental strain, mitochondria from isc1 Delta in the post-diauxic phase showed drastic reduction in the levels of alpha-hydroxylated phytoceramide (93.1% loss; compared to WT mitochondria with only 2.58 fold enrichment in mitochondria compared to whole cell). Functionally, isc1 Delta showed a higher rate of respiratory-deficient cells after incubation at high temperature and was more sensitive to hydrogen peroxide and ethidium bromide, indicating that isc1 Delta exhibits defects related to mitochondrial function. These results suggest that Isc1p generates ceramide in mitochondria, and the generated ceramide contributes to the normal function of mitochondria. This study provides a first insight into the specific composition of ceramides in mitochondria. (c) 2007 Elsevier B.V. All rights reserved. C1 Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Ralph H Johnson Vet Affairs Med Ctr, Charleston, SC 29401 USA. Minist Educ Culture Sports Sci & Technol, Chiyoda Ku, Tokyo, Japan. Natl Res Inst Brewing, Higashihiroshima, Hiroshima, Japan. RP Hannun, YA (reprint author), Med Univ S Carolina, Dept Biochem & Mol Biol, 173 Ashley Ave, Charleston, SC 29425 USA. EM hannun@musc.edu OI obeid, lina/0000-0002-0734-0847 FU NIA NIH HHS [R01 AG016583]; NIGMS NIH HHS [R37 GM043825-18, R37 GM043825, R01 GM043825, R01 GM43825] NR 62 TC 49 Z9 51 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0005-2736 J9 BBA-BIOMEMBRANES JI Biochim. Biophys. Acta-Biomembr. PD NOV PY 2007 VL 1768 IS 11 BP 2849 EP 2861 DI 10.1016/j.bbamem.2007.07.019 PG 13 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 239BT UT WOS:000251493700020 PM 17880915 ER PT J AU Law, B Weissleder, R Tung, CH AF Law, Benedict Weissleder, Ralph Tung, Ching-Hsuan TI Protease-sensitive fluorescent nanofibers SO BIOCONJUGATE CHEMISTRY LA English DT Article ID UROKINASE; NANOMEDICINES; PEPTIDES; DELIVERY; CANCER; DESIGN AB We report the design and synthesis of enzyme-responsive nanofibers. The fibers are composed of self-assembled hydrophobic beta-sheet peptides incorporating protease-sensitive domains, fluorescent reporters, and hydrophilic poly(ethylene glycol) (PEG) units. Using urokinase plasminogen activator (uPA) as a model system, nanofibers were developed to release fluorescent fragments upon uPA incubation. These protease-sensitive nanofibers may have considerable biomedical applications as diagnostic sensors or for protease-assisted drug deliveries. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. RP Tung, CH (reprint author), Methodist Hosp, Res Inst, Weill Cornell Med Coll, 6565 Fannin St,B5-022, Houston, TX 77030 USA. EM Shek.Law@NDSU.edu; ctung@tmhs.org OI Tung, Ching-Hsuan/0000-0001-6648-6195 FU NCI NIH HHS [P50 CA086355, P50 CA86355, R01 CA099385, R01 CA099385-04, R33 CA114149, R33 CA114149-02, R33 CA114149-03] NR 21 TC 40 Z9 40 U1 1 U2 11 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-DEC PY 2007 VL 18 IS 6 BP 1701 EP 1704 DI 10.1021/bc070054z PG 4 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 234LU UT WOS:000251166400002 PM 17915958 ER PT J AU Kim, GY Josephson, L Langer, R Cima, MJ AF Kim, Grace Y. Josephson, Lee Langer, Robert Cima, Michael J. TI Magnetic relaxation switch detection of human chorionic gonadotrophin SO BIOCONJUGATE CHEMISTRY LA English DT Article ID MRI CONTRAST AGENTS; NANOPARTICLES; IMMUNOASSAY; ASCITES; SERUM AB Functionalized nanoparticle contrast agents, also known as magnetic relaxation switches (MRS), were prepared to detect protein A and the beta subunit of human chorionic gonadotrophin (hCG-beta). Antibodies were attached to cross-linked iron oxide (CLIO) nanoparticles using standard peptide chemistry. Protein A was used as a simple model analyte, as it is naturally multivalent and can bind multiple CLIO-IgG simultaneously. The addition of PA to CLIO-IgG resulted in transverse relaxation time (T-2) shortening compared to a blank control as seen by NMR relaxometry measurements. Analyte-induced aggregation was confirmed by light scattering particle size analysis. A two-particle system was designed to measure hCG-beta, as it is not multivalent and requires conjugation of a matched pair of monoclonal antibodies to CLIO (referred to as C95 and C97). Measurement of hCG-beta is important, as elevated serum levels are associated with malignancies including testicular and ovarian cancers. The addition of hCG-beta to C95 and C97 resulted in T-2 shortening with a linear dynamic concentration range of 0.1 to 1 molecules of analyte per nanoparticle. Similar data were obtained for the hCG dimer. Observations with higher stoichiometric ratios of analyte to nanoparticle and increased nanoparticle valency were also made. This method can potentially be adapted to detect other biomarkers in solution. C1 MIT, Dept Mat Sci & Engn, Cambridge, MA 02139 USA. MIT, Dept Chem Engn, Cambridge, MA 02139 USA. MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Ctr Mol Imaging Res, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Cima, MJ (reprint author), MIT, Dept Mat Sci & Engn, 77 Massachusetts Ave,Room 12-011, Cambridge, MA 02139 USA. EM mjcima@mit.edu FU NCI NIH HHS [5 U54 CA119349-12] NR 20 TC 41 Z9 42 U1 1 U2 11 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-DEC PY 2007 VL 18 IS 6 BP 2024 EP 2028 DI 10.1021/bc070110w PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 234LU UT WOS:000251166400043 PM 17892270 ER PT J AU Biederman, J Boellner, SW Childress, A Lopez, FA Krishnan, S Zhang, YX AF Biederman, Joseph Boellner, Samuel W. Childress, Ann Lopez, Frank A. Krishnan, Suma Zhang, Yuxin TI Lisdexamfetamine dimesylate and mixed amphetamine salts extended-release in children with ADHD: A double-blind, placebo-controlled, crossover analog classroom study SO BIOLOGICAL PSYCHIATRY LA English DT Article DE ADHD; amphetamine; analog classroom; double blind; lisclexamfetamine; mixed amphetamine salts ID ATTENTION-DEFICIT/HYPERACTIVITY-DISORDER AB Background: Lisclexamfetamine dimesylate is a therapeutically inactive prodrug in which d-amphetamine is covalently bound to l-lysine, a naturally occurring amino acid. Pharmacologically active d-amphetamine is released from lisclexamfetarnine following oral ingestion. Methods: This phase 2, randomized, double-blind, placebo- and active-controlled crossover study compared the efficacy and safety of lisclexamfetamine (LDX: 30,50, or 70 mg) with placebo, with mixed amphetamine salts extended-release (MAS XR: 10, 20, or 30 mg) included as a reference arm of the study, in 52 children aged 6 to 12 years with attention-deficit/hyperactivity disorder (ADHD) in an analog classroom setting. The primary efficacy measure was the Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) Rating Scale; secondary efficacy measures included the Permanent Product Measure of Performance (PERMP) Derived Measures, and the Clinical Global Impression (CGI) Scale. Results: LDX treatment significantly improved scores on SKAMP-deportment, SKAMP-attention, PERMP-attempted, PERMP-correct, and CGI-improvement from baseline. Adverse events were similar for both active treatments. Conclusions: In a laboratory classroom environment, LDX significantly improved ADHD symptoms versus placebo in school-age children with ADHD. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Clin & Res Program,Pediat Psychopharmacol Unit A, Boston, MA 02114 USA. Clin Study Ctr, Little Rock, AR USA. Ctr Psychiat & Med Inc, Las Vegas, NV USA. Childrens Dev Ctr, Maitland, FL USA. New River Pharmaceut Inc, Blacksburg, VA USA. Xtiers Consulting, Potomac, MD USA. RP Biederman, J (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Clin & Res Program,Pediat Psychopharmacol Unit A, Boston, MA 02114 USA. EM biederman@helix.mgh.harvard.edu NR 14 TC 116 Z9 118 U1 0 U2 13 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 2007 VL 62 IS 9 BP 970 EP 976 DI 10.1016/j.biopsych.2007.04.015 PG 7 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 225OX UT WOS:000250528300005 PM 17631866 ER PT J AU Spencer, TJ Biederman, J Madras, BK Dougherty, DD Bonab, AA Livni, E Meltzer, PC Martin, J Rauch, S Fischman, AJ AF Spencer, Thomas J. Biederman, Joseph Madras, Bertha K. Dougherty, Darin D. Bonab, Ali A. Livni, Elijahu Meltzer, Peter C. Martin, Jessica Rauch, Scott Fischman, Alan J. TI Further evidence of dopamine transporter dysregulation in ADHD: A controlled PET imaging study using altropane SO BIOLOGICAL PSYCHIATRY LA English DT Article DE ADHD; dopamine; dopamine transporter (DAT); imaging; PET ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; AGE AB Background: The dopamine transporter (DAT) is known to be a key regulator of dopamine, and recent studies of genetics, treatment, and imaging have highlighted the role of DAT in attention-deficit/hyperactivity disorder (ADHD). The findings of in vivo neuroimaging of DAT in ADHD have been somewhat discrepant, however. Method: Dopamine transporter binding was measured using a highly selective ligand (C-11 altropane) and positron emission tomography (PET). The sample consisted of 47 well-characterized, treatment-naive, nonsmoking, non-comorbid adults with and without ADHD. Additionally, control subjects had few symptoms of ADHD. Results: Results showed significantly increased DAT binding in the right caudate in adults with ADHD compared with matched control subjects without this disorder. Conclusions: These results confirm abnormal DAT binding in the striatum of adults with ADHD and provide further support that dysregulation of DAT may be an important component of the pathophysiology of ADHD. C1 Massachusetts Gen Hosp, Pediat Psychopharmacol Unit ACC 725, Psychiat Serv, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Neurochem, New England Primate Res Ctr, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Nucl Med, Boston, MA 02115 USA. RP Spencer, TJ (reprint author), Massachusetts Gen Hosp, Pediat Psychopharmacol Unit ACC 725, Psychiat Serv, Fruit St, Boston, MA 02114 USA. EM tspencer@partners.org FU NIMH NIH HHS [R01 MH064019, R01 MH064019-01A2, R01 MH064019-02, R01 MH064019-03, R01 MH064019-04, R01 MH064019-05, R01MH064019] NR 17 TC 80 Z9 84 U1 2 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD NOV 1 PY 2007 VL 62 IS 9 BP 1059 EP 1061 DI 10.1016/j.biopsych.2006.12.008 PG 3 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 225OX UT WOS:000250528300017 PM 17511972 ER PT J AU Ferrara, JLM Anasetti, C Stadtmauer, E Antin, J Wingard, J Lee, S Levine, J Schultz, K Appelbaum, F Negrin, R Giralt, S Bredeson, C Heslop, H Horowitz, M AF Ferrara, James L. M. Anasetti, Claudio Stadtmauer, Edward Antin, Joseph Wingard, John Lee, Stephanie Levine, John Schultz, Kirk Appelbaum, Frederick Negrin, Robert Giralt, Sergio Bredeson, Christopher Heslop, Helen Horowitz, Mary TI Blood and marrow transplant clinical trials network state of the science symposium 2007 SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Editorial Material DE hematopoietic cell transplantation; clinical trials network; clinical trials; graft versus host disease; acute myeloid leukemia; acute lymphocytic leukemia; chronic lymphocytic leukemia; T cell lymphoma; hemaphogocytic lymphohistiocytosis; Crohn's disease; cell therapy; biomarkers; quality of life ID STEM-CELL TRANSPLANTATION; VERSUS-HOST-DISEASE; ACUTE LYMPHOBLASTIC-LEUKEMIA; ANTIGEN-PRESENTING CELLS; PNEUMOCOCCAL CONJUGATE VACCINE; PROTECTIVE ANTIBODY-RESPONSES; KERATINOCYTE GROWTH-FACTOR; ACUTE MYELOID-LEUKEMIA; PHASE-II TRIALS; TERM-FOLLOW-UP AB Outcomes of henratopoietic cell transplantation are steadily improving. New techniques have reduced transplant toxicities, and there are new sources of hematopoietic stem cells from unrelated donors. Injune 2007 the Blood and Marrow Transplant Clinical Trials Network convened a State of the Science Symposium of more than 200 participants in Ann Arbor to identify the most compelling clinical research opportunities in the field. This report summarizes the symposium's discussions and identifies eleven high priority clinical trials that the network plans to pursue over the course of the next several years. (c) 2007 Anierican Society jor Blood and Mai-row Transplantation C1 Univ Michigan, Ann Arbor, MI 48109 USA. Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. Univ Penn, Philadelphia, PA 19104 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Florida, Shands Canc Ctr, Gainesville, FL USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ British Columbia, BC Childrens Hosp, Vancouver, BC V5Z 1M9, Canada. Stanford Univ, Stanford, CA 94305 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. Baylor Coll Med, Houston, TX 77030 USA. CIBMTR, Milwaukee, WI USA. RP Ferrara, JLM (reprint author), 1500 E Med Ctr Dr,6303 Canc Ctr, Ann Arbor, MI USA. EM ferrara@umich.edu OI Levine, John/0000-0002-9133-0800 FU NCI NIH HHS [U24 CA076518]; NHLBI NIH HHS [U10 HL069254, U10 HL069301, U10 HL069330, U10 HL069294, U10 HL069249, 1 R13 HL88882-01] NR 116 TC 15 Z9 16 U1 6 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 EI 1523-6536 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD NOV PY 2007 VL 13 IS 11 BP 1268 EP 1285 DI 10.1016/j.bbmt.2007.08.005 PG 18 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 229OE UT WOS:000250813000002 PM 17950914 ER PT J AU Scadden, D AF Scadden, David TI Therapeutic manipulation of the stem cell niche SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT 5th Annual International Umbilical Cord Blood Transplantation Symposium CY MAY 11-12, 2007 CL Los Angeles, CA SP Calif Blood Bank Soc, Cord Blood Forum C1 Massachusetts Gen Hosp, Harvard Stem Cell Inst, Boston, MA 02114 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 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD NOV PY 2007 VL 13 IS 11 MA 11 BP 1396 EP 1397 DI 10.1016/j.bbmt.2007.08.019 PG 2 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 229OE UT WOS:000250813000024 ER PT J AU Ballen, K Cutler, C Yeap, BY McAfee, SL Dey, BR Attar, EC Haspel, RL Liney, D Koreth, O Ho, V Alyea, EP Soiffer, RJ Spitzer, TR Antin, AH AF Ballen, Kaven Cutler, Corey Yeap, Beow Y. McAfee, Steven L. Dey, Bimalangshu R. Attar, Eyal C. Haspel, Ricbard L. Liney, Deborab Koreth, Obn Ho, Vincent Alyea, Edwin P. Soiffer, Robert J. Spitzer, Tboinas R. Antin, Andjoseph H. TI Double reduced intensity cord blood transplants in adults SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Meeting Abstract CT 5th Annual International Umbilical Cord Blood Transplantation Symposium CY MAY 11-12, 2007 CL Los Angeles, CA SP Calif Blood Bank Soc, Cord Blood Forum 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 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 2007 VL 13 IS 11 MA 17 BP 1398 EP 1399 DI 10.1016/j.bbmt.2007.08.025 PG 2 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 229OE UT WOS:000250813000030 ER PT J AU Shivdasani, RA AF Shivdasani, Ramesh A. TI My, oh Myh9 ... and platelets, too SO BLOOD LA English DT Editorial Material C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Shivdasani, RA (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 4 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 1 PY 2007 VL 110 IS 9 BP 3093 EP 3093 DI 10.1182/blood-2007-08-105460 PG 1 WC Hematology SC Hematology GA 230UJ UT WOS:000250901200006 ER PT J AU Jiang, Y Borrelli, L Kanaoka, Y Bacskal, BJ Boyce, JA AF Jiang, Yongfeng Borrelli, LauraA. Kanaoka, Yoshihide Bacskal, Brian J. Boyce, Joshua A. TI CysLT(2) receptors interact with CysLT(1) receptors and down-modulate cysteinyl leukotriene-dependent mitogenic responses of mast cells SO BLOOD LA English DT Article ID GENE DISRUPTION REVEALS; VASCULAR-PERMEABILITY; PULMONARY INFLAMMATION; ASTHMATIC SUBJECTS; CUTTING EDGE; EXPRESSION; MICE; BRONCHOCONSTRICTION; PROLIFERATION; ANTAGONISTS AB Cysteinyl leukotrienes (cys-LTs) induce inflammation through 2 G protein-coupled receptors (GPCRs), CysLT(1) and CysLT(2), which are coexpressed by most myeloid cells. Cys-LTs induce proliferation of mast cells (MCs), transactivate c-Kit, and phosphorylate extracellular signal-regulated kinase (ERK). Although MCs express CysLT(2), their responses to cys-LTs are blocked by antagonists of CysLT(1). We demonstrate that CysLT(2) interacts with CysLT(1), and that knockdown of CysLT(2) increases CysLT1 surface expression and CysLT(1)-dependent proliferation of cord blood-derived human MCs (hMCs). Cys-LT-mediated responses were absent in MCs from mice lacking CysLT(1) receptors, but enhanced by the absence of CysLT(2) receptors. CysLT(1) and CysLT(2) receptors colocalized to the plasma membranes and nuclei of a human MC line, LAD2. Antibody-based fluorescent lifetime imaging microscopy confirmed complexes containing both receptors based on fluorescence energy transfer. Negative regulation of CysLT(1)-induced mitogenic signaling responses of MCs by CysLT(2) demonstrates physiologically relevant functions for GPCR heterodimers on primary cells central to inflammation. C1 Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Neurol, MassGen Inst Neurodegenerat Dis, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Jiang, Y (reprint author), 1 Jimmy Fund Way,Smith Bldg Rm 626, Boston, MA 02115 USA. FU NHLBI NIH HHS [HL 36110, P01 HL036110]; NIAID NIH HHS [AI 48802, AI 52353, P01 AI031599, R37 AI052353, U19 AI031599, R56 AI052353, R01 AI052353, R01 AI048802, AI 31599]; NIBIB NIH HHS [EB 00768, R01 EB000768] NR 35 TC 81 Z9 86 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 1 PY 2007 VL 110 IS 9 BP 3263 EP 3270 DI 10.1182/blood-2007-07-100453 PG 8 WC Hematology SC Hematology GA 230UJ UT WOS:000250901200029 PM 17693579 ER PT J AU Kveraga, K Ghuman, AS Bar, M AF Kveraga, Kestutis Ghuman, Avniel S. Bar, Moshe TI Top-down predictions in the cognitive brain SO BRAIN AND COGNITION LA English DT Review DE vision; visual pathways; magnocellular; parvocellular; object recognition; computational methods; priming; synchrony; contextual facilitation; orbitofrontal cortex; neuroimaging; magnetoencephalography ID VISUAL OBJECT RECOGNITION; EVENT-RELATED FMRI; LATERAL GENICULATE-NUCLEUS; HUMAN EXTRASTRIATE CORTEX; MEDIAL PREFRONTAL CORTEX; EMOTIONAL FACIAL EXPRESSIONS; POSTERIOR-PULVINAR COMPLEX; CLASSICAL RECEPTIVE-FIELD; MULTIPLE CORTICAL AREAS; MACAQUE MONKEY AB The human brain is not a passive organ simply waiting to be activated by external stimuli. Instead, we propose that the brain continuously employs memory of past experiences to interpret sensory information and predict the immediately relevant future. The basic elements of this proposal include analogical mapping, associative representations and the generation of predictions. This review concentrates on visual recognition as the model system for developing and testing ideas about the role and mechanisms of top-down predictions in the brain. We cover relevant behavioral, computational and neural aspects, explore links to emotion and action preparation, and consider clinical implications for schizophrenia and dyslexia. We then discuss the extension of the general principles of this proposal to other cognitive domains. (C) 2007 Elsevier Inc. All rights reserved. C1 [Kveraga, Kestutis; Ghuman, Avniel S.; Bar, Moshe] Massachusetts Gen Hosp, Harvard Med Sch, Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Bar, M (reprint author), Massachusetts Gen Hosp, Harvard Med Sch, Martinos Ctr Biomed Imaging, 149 Thirteen St, Charlestown, MA 02129 USA. EM bar@nmr.mgh.harvard.edu OI Ghuman, Avniel/0000-0003-1746-4656 FU NINDS NIH HHS [R01 NS050615-04, NS050615, R01 NS044319, R01 NS044319-03, R01 NS050615, R01-NS044319] NR 258 TC 148 Z9 157 U1 6 U2 33 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0278-2626 J9 BRAIN COGNITION JI Brain Cogn. PD NOV PY 2007 VL 65 IS 2 BP 145 EP 168 DI 10.1016/j.bandc.2007.06.007 PG 24 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 240BN UT WOS:000251562100002 PM 17923222 ER PT J AU Kuter, DJ Bain, B Mufti, G Bagg, A Hasserjian, RP AF Kuter, David J. Bain, Barbara Mufti, Ghulam Bagg, Adam Hasserjian, Robert P. TI Bone marrow fibrosis: pathophysiology and clinical significance of increased bone marrow stromal fibres SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Review DE reticulin; collagen; myelofibrosis; myeloproliferative disease; thrombopoietin ID GROWTH-FACTOR-BETA; CHRONIC MYELOPROLIFERATIVE DISORDERS; CHRONIC IDIOPATHIC MYELOFIBROSIS; COLONY-STIMULATING FACTOR; HEMATOPOIETIC-CELL TRANSPLANTATION; CHRONIC MYELOGENOUS LEUKEMIA; INTERNATIONAL-WORKING-GROUP; PLATELET ALPHA-GRANULES; TREATMENT IWG-MRT; MYELOID METAPLASIA AB In bone marrow biopsies, stromal structural fibres are detected by reticulin and trichrome stains, routine stains performed on bone marrow biopsy specimens in diagnostic laboratories. Increased reticulin staining (reticulin fibrosis) is associated with many benign and malignant conditions while increased trichrome staining (collagen fibrosis) is particularly prominent in late stages of severe myeloproliferative diseases or following tumour metastasis to the bone marrow. Recent evidence has shown that the amount of bone marrow reticulin staining often exhibits no correlation to disease severity, while the presence of type 1 collagen, as detected by trichrome staining, is often associated with more severe disease and a poorer prognosis. It was originally thought that increases in bone marrow stromal fibres themselves contributed to the haematopoietic abnormalities seen in certain diseases, but recent studies suggest that these increases are a result of underlying cellular abnormalities rather than a cause. A growing body of evidence suggests that increased deposition of bone marrow stromal fibres is mediated by transforming growth factor-beta and other factors elaborated by megakaryocytes, but it is likely that other cells, cytokines and growth factors are also involved. This suggests new avenues for investigation into the pathogenesis of various disorders associated with increased bone marrow stromal fibres. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. St Marys Hosp, London, England. Kings Coll Hosp, London, England. Penn State Univ Hosp, Philadelphia, PA USA. RP Kuter, DJ (reprint author), Massachusetts Gen Hosp, Div Hematol, Yawkey 7940, 55 Fruit Str, Boston, MA 02114 USA. EM kuter.david@mgh.harvard.edu FU NHLBI NIH HHS [HL72299, HL82889] NR 98 TC 96 Z9 100 U1 2 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD NOV PY 2007 VL 139 IS 3 BP 351 EP 362 DI 10.1111/j.1365-2141.2007.06807.x PG 12 WC Hematology SC Hematology GA 216LY UT WOS:000249880700001 PM 17910625 ER PT J AU Punglia, RS Cullen, J McLeod, DG Chen, Y D'Amico, AV AF Punglia, Rinaa S. Cullen, Jennifer McLeod, David G. Chen, Yongmei D'Amico, Anthony V. TI Prostate-specific antigen velocity and the detection of Gleason score 7 to 10 prostate cancer SO CANCER LA English DT Article DE cancer detection; Gleason score; prostate cancer; prostate-specific antigen ID RADICAL PROSTATECTOMY; PSA VELOCITY; RISK; DISEASE; DEATH AB BACKGROUND. An increasing prostate-specific antigen (PSA) velocity is associated with a shorter survival after local therapy for prostate cancer. In this study, the authors evaluated whether PSA velocity was associated with prostate cancer detection and grade at diagnosis after adjusting for established predictors. METHODS. Between January 1989 and December 2003, 914 men who had PSA levels >= 4 ng/mL were identified by using the Center for Prostate Disease Research (CPDR) multicenter national database, including 541 men who were diagnosed with prostate cancer. Multivariable logistic regression analyses were performed that included continuous variables (PSA velocity and level, number of prior negative biopsies, and age) along with categorical variables (ethnicity and family history) were used to identify the factors associated with prostate cancer detection and grade. RESULTS. An increasing PSA velocity was associated with Gleason scores from 7 to 10 versus Gleason scores form 2 to 6 or no cancer (adjusted odds ratio [OR], 1.04 ng/mL per year; 95% confidence interval [95% CI], 1.003-1.085 ng/mL per year; P =.035). This finding was not evident in patients who had prostate cancers with Gleason scores between 2 and 6 or for any prostate cancer. PSA level was associated with the detection of any prostate cancer (OR, 1.06 ng/mL; 95% Cl, 1.03-1.10 ng/mL; P =.004) and Gleason score <= 6 prostate cancer (OR, 1.06 ng/ mL; 95% Cl, 1.02-1.10 ng/mL; P =.0027); however, in the presence of PSA velocity, PSA no longer remained independently predictive for high-grade prostate cancer (OR, 1.01 ng/mL; 95% Cl, 0.98-1.04 ng/mL; P =.45) after adjusting for established predictors. CONCLUSIONS. PSA velocity enhanced the detection of high-grade cancer in men who had PSA levels > 4 ng/mL. These findings, in conjunction with life expectancy, may be used when deciding which men should not be recommended for prostate biopsy despite a PSA level > 4 ng/mL. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Uniformed Serv Univ Hlth Sci, Dept Surg, Rockville, MD USA. Ctr Prostate Dis Res, Rockville, MD USA. Walter Reed Army Med Ctr, Dept Urol, Bethesda, MD USA. RP Punglia, RS (reprint author), Dana Farber Canc Inst, Smith 274,44 Binney St, Boston, MA 02115 USA. EM rpunglia@partners.org NR 15 TC 14 Z9 14 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD NOV 1 PY 2007 VL 110 IS 9 BP 1973 EP 1978 DI 10.1002/cncr.23014 PG 6 WC Oncology SC Oncology GA 224CE UT WOS:000250422500012 PM 17886252 ER PT J AU Gutierrez, A Look, T AF Gutierrez, Alejandro Look, Thomas TI NOTCH and PI3K-AKT pathways intertwined SO CANCER CELL LA English DT Editorial Material ID ACUTE LYMPHOBLASTIC-LEUKEMIA; T-CELL LEUKEMIA; C-MYC; RESISTANCE; ACTIVATION; MUTATIONS AB Constitutive signaling by the NOTCH1 receptor contributes to more than half of all cases of T cell acute lymphoblastic leukemia (T-ALL). However, blocking the proteolytic activation of NOTCH1 with gamma-secretase inhibitors (GSIs) fails to alter the growth of some T-ALL cell lines carrying the mutated receptor. A recent report by Palomero et al. in Nature Medicine identifies loss of PTEN as a critical event leading to resistance to NOTCH inhibition, which causes the transfer of "oncogene addiction" from the NOTCH1 to the PI3K/AKT pathway. This novel observation suggests the need to simultaneously inhibit both pathways as a means to improve therapeutic efficacy in human T-ALL. C1 Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. RP Look, T (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. EM thomas_look@dfci.harvard.edu OI Gutierrez, Alejandro/0000-0002-0249-9007 NR 12 TC 63 Z9 71 U1 1 U2 5 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 2007 VL 12 IS 5 BP 411 EP 413 DI 10.1016/j.ccr.2007.10.027 PG 3 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 232GQ UT WOS:000251006900004 PM 17996644 ER PT J AU Emmons, KM White, KB Benz, EJ AF Emmons, Karen M. White, Karen Bums Benz, Edward J. TI Development of an integrated approach to cancer disparities: One cancer center's experience SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Editorial Material ID LUNG-CANCER; AFRICAN-AMERICANS; NICOTINE; RISK C1 Harvard Univ, Sch Publ Hlth, Ctr Community Based Res, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Dana Farber Harvard Canc Ctr, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP Emmons, KM (reprint author), Harvard Univ, Sch Publ Hlth, Ctr Community Based Res, 44 Binney St, Boston, MA 02115 USA. EM Karen_M_Emmons@dfci.harvard.edu FU NCCDPHP CDC HHS [U48 DP000064]; NCI NIH HHS [U01 CA114644, P30 CA06516, P30 CA006516] NR 12 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2007 VL 16 IS 11 BP 2186 EP 2192 DI 10.1158/1055-9965.EFI-07-0211 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 233XL UT WOS:000251123500004 PM 18006905 ER PT J AU McIntyre, MH Kantoff, PW Stampfer, MJ Mucci, LA Parslow, D Li, H Gaziano, JM Abe, M Ma, J AF McIntyre, Matthew H. Kantoff, Philip W. Stampfer, Meir J. Mucci, Lorelei A. Parslow, Diane Li, Haojie Gaziano, J. Michael Abe, Miyako Ma, Jing TI Prostate cancer risk and ESR1 TA, ESR2 CA repeat polymorphisms SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID ESTROGEN-RECEPTOR-ALPHA; BONE-MINERAL DENSITY; CORONARY-ARTERY-DISEASE; GENE POLYMORPHISMS; ENDOMETRIAL CANCER; POSTMENOPAUSAL WOMEN; BETA-GENE; ASSOCIATION; ANDROGEN; HAPLOTYPES AB Background: Experimental evidence has suggested that estrogen receptor alpha (coded by the gene ESR1) might increase prostate cancer risk, whereas estrogen receptor beta (coded by the gene ESR2) might reduce prostate cancer risk. Methods: We investigated the relationship with prostate cancer risk of both a TA repeat polymorphism in the ESR1 5' region, ESR1 (TA)(n), and with a CA repeat polymorphism in intron 5 of ESR2, ESR2 (CA)(n), in a case-control study (545 cases and 674 controls) nested in the Physicians' Health Study. Results: Prostate cancer risk was highest for carriers of ESR1 (TA)(24) and ESR1 (TA)(25). Replacing one modal ESR1 (TA)(14) allele with one ESR1 (TA)(24) allele yielded an odds ratio of 1.42 (95% confidence interval, 1.00-2.00; P = 0.05). Replacing one ESR1 (TA)(14) allele with one ESR1 (TA)(25) allele yielded an odds ratio of 2.10 (95% confidence interval, 1.15-3.84; P = 0.02). ESR2 (CA), showed no effects on prostate cancer risk. Conclusions: The ESR1 (TA)(n) polymorphism might play a role in prostate cancer risk. C1 Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA. Univ Cent Florida, Dept Anthropol, Orlando, FL 32816 USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. RP McIntyre, MH (reprint author), Brigham & Womens Hosp, Dept Med, Channing Lab, 181 Longwood Ave, Boston, MA 02115 USA. EM m.ncintyr@mail.ucf.edu RI McIntyre, Matthew/B-6266-2009 FU NCI NIH HHS [CA009001, R01 CA097193, CA058684] NR 29 TC 14 Z9 16 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2007 VL 16 IS 11 BP 2233 EP 2236 DI 10.1158/1055-9965.EPI-07-0481 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 233XL UT WOS:000251123500012 PM 18006911 ER PT J AU Setiawan, VW Schumacher, FR Haiman, CA Stram, DO Albanes, D Altshuler, D Berglund, G Buring, J Calle, EE Clavel-Chapelon, F Cox, DG Gaziano, JM Hankinson, SE Hayes, RB Henderson, BE Hirschhorn, J Hoover, R Hunter, DJ Kaaks, R Kolonel, LN Kraft, P Ma, J Le Marchand, L Linseisen, J Lund, E Navarro, C Overvad, K Palli, D Peeters, PHM Pike, MC Riboli, E Stampfer, MJ Thun, MJ Travis, R Trichopoulos, D Yeager, M Ziegler, RG Feigelson, HS Chanock, SJ AF Setiawan, Veronica Wendy Schumacher, Fredrick R. Haiman, Christopher A. Stram, Daniel O. Albanes, Demetrius Altshuler, David Berglund, Gran Buring, Julie Calle, Eugenia E. Clavel-Chapelon, Francoise Cox, David G. Gaziano, J. Michael Hankinson, Susan E. Hayes, Richard B. Henderson, Brian E. Hirschhorn, Joel Hoover, Robert Hunter, David J. Kaaks, Rudolf Kolonel, Laurence N. Kraft, Peter Ma, Jing Le Marchand, Loic Linseisen, Jakob Lund, Eiliv Navarro, Carmen Overvad, Kim Palli, Domenico Peeters, Petra H. M. Pike, Malcolm C. Riboli, Elio Stampfer, Meir J. Thun, Michael J. Travis, Ruth Trichopoulos, Dimitrios Yeager, Meredith Ziegler, Regina G. Feigelson, Heather Spencer Chanock, Stephen J. TI CYP17 genetic variation and risk of breast and prostate cancer from the national Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3) SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID ANDROGEN RECEPTOR GENE; POSTMENOPAUSAL WOMEN; HORMONE-LEVELS; MULTIETHNIC COHORT; BRAZILIAN PATIENTS; SERUM ANDROGENS; POLYMORPHISMS; ASSOCIATION; METAANALYSIS; DEFICIENCY AB CYP17 encodes cytochrome p450c17 alpha, which mediates activities essential for the production of sex steroids. Common germ line variation in the CYP17 gene has been related to inconsistent results in breast and prostate cancer, with most studies focusing on the nonsynonymous single nucleotide polymorphism (SNP) T27C (rs743572). We comprehensively characterized variation in CYP17 by direct sequencing of exons followed by dense genotyping across the 58 kb region around CYP17 in five racial/ethnic populations. Two blocks of strong linkage disequilibrium were identified and nine haplotype-tagging SNPs, including T27C, were chosen to predict common haplotypes (R-h(2) >= 0.85). These haplotype-tagging SNPs were genotyped in 8,138 prostate cancer cases and 9,033 controls, and 5,333 breast cancer cases and 7,069 controls from the Breast and Prostate Cancer Cohort Consortium. We observed borderline significant associations with prostate cancer for rs2486758 [TC versus TT, odds ratios (OR), 1.07; 95% confidence intervals (95% Cl), 1.00-1.14; CC versus TT, OR, 1.09; 95% CI, 0.95-1.26; P trend = 0.04] and rs6892 (AG versus AA, OR, 1.08; 95% CI, 1.00-1.15; GG versus AA, OR, 1.11; 95% CI, 0.95-1.30; P trend = 0.03). We also observed marginally significant associations with breast cancer for rs4919687 (GA versus GG, OR, 1.04; 95% CI, 0.97-1.12, AA versus GG, OR, 1.17; 95% CI, 1.03-1.34; P trend = 0.03) and rs4919682 (CT versus CC, OR, 1.04; 95% CI, 0.97-1.12; TT versus CC, OR, 1.16; 95% CI, 1.01-1.33; P trend = 0.04). Common variation at CYP17 was not associated with circulating sex steroid hormones in men or postmenopausal women. Our findings do not support the hypothesis that common germ line variation in CYP17 makes a substantial contribution to postmenopausal breast or prostate cancer susceptibility. C1 Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Dept Prevent Med, Los Angeles, CA 90033 USA. Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. Broad Inst Harvard, Cambridge, MA USA. MIT, Cambridge, MA 02139 USA. Malmo Univ Hosp, Dept Clin Sci, Malmo, Sweden. Brigham & Womens Hosp, Div Prevent Med, Boston, MA USA. Brigham & Womens Hosp, Div Aging, Boston, MA USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. Amer Canc Soc, Atlanta, GA 30329 USA. Inst Gustave Roussy, INSERM, F-94805 Villejuif, France. VA Boston Healthcare Syst, Boston, MA USA. German Canc Res Ctr, Div Canc Epidemiol, D-6900 Heidelberg, Germany. Univ Hawaii, Canc Res Ctr, Program Epidemiol, Honolulu, HI 96822 USA. Univ Tromso, Inst Community Med, Tromso, Norway. Murcia Hlth Council, Dept Epidemiol, Murcia, Spain. Aarhus Univ Hosp, Aalborg Hosp, Aalborg, Denmark. SCPO Sci Inst Tuscany, Mol & Nutr Epidemiol Unit, Florence, Italy. Univ Med Ctr, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands. Univ London Imperial Coll Sci Technol & Med, London, England. Univ Oxford, Canc Epidemiol Unit, Oxford, England. RP Setiawan, VW (reprint author), Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Dept Prevent Med, 1441 Eastlake Ave,Room 4425, Los Angeles, CA 90033 USA. EM vsetiawa@usc.edu RI Cox, David/A-2023-2009; Altshuler, David/A-4476-2009; Linseisen, Jakob/B-5353-2014; Clavel-Chapelon, Francoise/G-6733-2014; Albanes, Demetrius/B-9749-2015; OI Cox, David/0000-0002-2152-9259; Altshuler, David/0000-0002-7250-4107; Linseisen, Jakob/0000-0002-9386-382X; Hayes, Richard/0000-0002-0918-661X; PALLI, Domenico/0000-0002-5558-2437 FU Intramural NIH HHS; NCI NIH HHS [CA116543, R01 CA097193, UO1-CA98216, UO1-CA98233, UO1-CA98710, UO1-CA98758] NR 36 TC 40 Z9 41 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 EI 1538-7755 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2007 VL 16 IS 11 BP 2237 EP 2246 DI 10.1158/1055-9965.EPI-07-0589 PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 233XL UT WOS:000251123500013 PM 18006912 ER PT J AU Miller, YE Blatchford, P Hyun, DS Keith, RL Kennedy, TC Wolf, H Byers, T Bunn, PA Lewis, MT Franklin, WA Hirsch, FR Kittelson, J AF Miller, York E. Blatchford, Patrick Hyun, Dae Sung Keith, Robert L. Kennedy, Timothy C. Wolf, Holly Byers, Tim Bunn, Paul A., Jr. Lewis, Marina T. Franklin, Wilbur A. Hirsch, Fred R. Kittelson, John TI Bronchial epithelial Ki-67 index is related to histology, smoking, and gender, but not lung cancer or chronic obstructive pulmonary disease SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID PRENEOPLASTIC LESIONS; PROMOTER HYPERMETHYLATION; RESPIRATORY EPITHELIUM; SMOKERS; RISK; PROLIFERATION; CHEMOPREVENTION; EXPRESSION; CARCINOMA; COHORT AB Purpose: To determine whether increased bronchial epithelial proliferation is associated with histology, smoking status, gender, age, chronic obstructive pulmonary disease (COPD), or lung cancer. Experimental Design: Cross-sectional study of 113 subjects undergoing white light and autofluorescence bronchoscopy: 27 never smokers; 27 current or ex-smokers with normal spirometry; 31 current or ex-smokers with COPD; and 28 current, ex-, or never smokers with lung cancer. Ki-67 expresssion was determined by immunohistochemistry on all evaluable biopsy sites without carcinoma. Relationships between Ki-67 index (percentage of epithelial cells expressing Ki-67), demographic variables, smoking, histology, and the presence of COPD and/or lung cancer were determined. Results: Results for both maximal and mean Ki-67 index are similar, so only the former are reported. Average maximal Ki-67 index was higher in current smokers than either ex-smokers or never smokers (48.0% versus 30.6% versus 22.6%; P < 0.001). Males had higher Ki-67 index than females (39.9% versus 23.6%; P < 0.001). Compared with subjects without disease (Ki-67 index = 30.0%), maximal Ki-67 index was not significantly elevated (P = 0.44) in subjects with either lung cancer (Ki-67 = 39.1%) or COPD (Ki-67 = 38.9%). Conclusions: Smoking status, bronchial histology, and gender were significantly associated with Ki-67 index. No increase in Ki-67 index was found in the nonmalignant epithelium of patients with lung cancer or COPD. Although Ki-67 index may provide insight into the short-term effects of chemoprevention agents on cell proliferation, its lack of association with lung cancer or COPD raises question regarding its utility as a lung cancer risk biomarker. C1 Univ Colorado, Ctr Comprehens Canc, Univ Colorado Denver & Hlth Sci Ctr, Dept Prevent Med & Biometr, Denver, CO 80202 USA. Univ Colorado, Ctr Comprehens Canc, Univ Colorado Denver & Hlth Sci Ctr, Dept Med, Denver, CO 80202 USA. Univ Colorado, Ctr Comprehens Canc, Univ Colorado Denver & Hlth Sci Ctr, Div Med Oncol,Dept Med, Denver, CO 80202 USA. Univ Colorado, Ctr Comprehens Canc, Univ Colorado Denver & Hlth Sci Ctr, Dept Pathol, Denver, CO 80202 USA. Univ Colorado, Univ Colorado Denver & Hlth Sci Ctr, Dept Med,Div Pulm Sci & Crit, Denver Vet Affairs Med Ctr,Comprehens Canc Ctr, Denver, CO 80220 USA. Catholic Univ Daegu, Taegu, South Korea. RP Miller, YE (reprint author), Univ Colorado, Univ Colorado Denver & Hlth Sci Ctr, Dept Med,Div Pulm Sci & Crit, Denver Vet Affairs Med Ctr,Comprehens Canc Ctr, Pulm 111A,1055 Clermont St, Denver, CO 80220 USA. EM york.miller@uchsc.edu FU NCI NIH HHS [P50CA58187, P30CA46934] NR 29 TC 16 Z9 16 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2007 VL 16 IS 11 BP 2425 EP 2431 DI 10.1158/1055-9965.EPI-07-0220 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 233XL UT WOS:000251123500035 PM 18006932 ER PT J AU Greshock, J Feng, B Nogueira, C Ivanova, E Perna, I Nathanson, K Protopopov, A Weber, BL Chin, L AF Greshock, Joel Feng, Bin Nogueira, Cristina Ivanova, Elena Perna, Ilana Nathanson, Katherine Protopopov, Alexei Weber, Barbara L. Chin, Lynda TI A comparison of DNA copy number profiling platforms SO CANCER RESEARCH LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; HIGH-RESOLUTION ANALYSIS; MICROARRAYS; DIFFERENTIATION; CHILDHOOD; REVEALS; PROGRAM; CANCER AB The accurate mapping of recurring DNA copy number aberrations (CNAs), a hallmark feature of the cancer genome, has facilitated the discovery of tumor suppressor genes and oncogenes. Microarray-based assays designed to detect these chromosomal copy number alterations on a genome-wide and high-resolution scale have emerged as a cornerstone technology in the genomic era. The diversity of commercially available platforms prompted a systematic comparison of five copy number profiling assays for their ability to detect 2-fold copy number gain and loss (4n or 1n, respectively) as well as focal high-amplitude CNAs. Here, using a collection of established human melanoma cell lines, we defined the reproducibility, absolute signals, signal to noise, and false-positive and false-negative rates for each of the five assays against ground truth defined by spectral karyotyping, in addition to comparing the concordance of CNA detection by two high-resolution Agilent and Affymetrix microarray platforms. Our analyses concluded that the Agilent's 60-mer oligonucleotide microarray with probe design optimized for genomic hybridization offers the highest sensitivity and specificity (area under receiver operator characteristic curve >0.99), whereas Affymetrix's single nucleotide polymorphism microarray seems to offer better detection of CNAs in gene-poor regions. Availability of these comparison results should guide study design decisions and facilitate further computational development. C1 Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. GlaxoSmithKline Inc, Translat Med, King Of Prussia, PA USA. Belfer Inst Innovat Canc Sci, Ctr Appl Canc Sci, Boston, MA USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. Univ Penn, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA. RP Chin, L (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM lynda_Chin@dfci.harvard.edu RI Nogueira, Cristina/N-4574-2015; OI Nogueira, Cristina/0000-0002-0853-5304; Nathanson, Katherine/0000-0002-6740-0901 FU NCI NIH HHS [P01 CA095616, P01 CA095616-01A19003, P50 CA93638, R01 CA093947, R01 CA093947-06, R01 CA93947, R01 CA99041, U24 CA126554] NR 19 TC 50 Z9 52 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 1 PY 2007 VL 67 IS 21 BP 10173 EP 10180 DI 10.1158/0008-5472.CAN-07-2102 PG 8 WC Oncology SC Oncology GA 228AV UT WOS:000250700200012 PM 17968032 ER PT J AU Setlur, SR Royce, TE Sboner, A Mosquera, JM Demichelis, F Hofer, MD Mertz, KD Gerstein, M Rubin, MA AF Setlur, Sunita R. Royce, Thomas E. Sboner, Andrea Mosquera, Juan Miguel Demichelis, Francesca Hofer, Matthias D. Mertz, Kirsten D. Gerstein, Mark Rubin, Mark A. TI Integrative Microarray analysis of pathways dysregulated in metastatic prostate cancer SO CANCER RESEARCH LA English DT Article ID NF-KAPPA-B; GENE SET ENRICHMENT; LYMPH-NODE METASTASES; CONSTITUTIVE ACTIVATION; NUCLEAR-LOCALIZATION; TRANSCRIPTION FACTOR; EXPRESSION PROFILES; PROGRESSION; CELLS; ADENOCARCINOMA AB Microarrays have been used to identify genes involved in cancer progression. We have now developed an algorithm that identifies dysregulated pathways from multiple expression array data sets without a priori definition of gene expression thresholds. Integrative microarray analysis of pathways (IMAP) was done using existing expression array data from localized and metastatic prostate cancer. Comparison of metastatic cancer and localized disease in multiple expression array profiling studies using the IMAP approach yielded a list of about 100 pathways that were significantly dysregulated (P < 0.05) in prostate cancer metastasis. The pathway that showed the most significant dysregulation, HIV-1 NEF, was validated at both the transcript level and the protein level by quantitative PCR and immunohistochemical analysis, respectively. Validation by unsupervised analysis on an independent data set using the gene expression signature from the HIV-1 NEF pathway verified the accuracy of our method. Our results indicate that this pathway is especially dysregulated in hormone-refractory prostate cancer. C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT USA. Yale Univ, Program Computat Biol & Bioinformat, New Haven, CT USA. Yale Univ, Dept Comp Sci, New Haven, CT USA. Broad Inst MIT & Harvard, Cambridge, MA USA. RP Rubin, MA (reprint author), Weill Cornell Med Coll, Dept Pathol & Lab Med, 1300 York Ave, New York, NY 10021 USA. EM rubinma@med.cornell.edu RI Sboner, Andrea/C-6487-2008; OI Sboner, Andrea/0000-0001-6915-3070; Rubin, Mark/0000-0002-8321-9950; Demichelis, Francesca/0000-0002-8266-8631 NR 39 TC 51 Z9 52 U1 2 U2 4 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 2007 VL 67 IS 21 BP 10296 EP 10303 DI 10.1158/0008-5472.CAN-07-2173 PG 8 WC Oncology SC Oncology GA 228AV UT WOS:000250700200026 PM 17974971 ER PT J AU Viswanathan, AN Hankinson, SE Schernhammer, ES AF Viswanathan, Akija N. Hankinson, Susan E. Schernhammer, Eva S. TI Night shift work and the risk of endometrial cancer SO CANCER RESEARCH LA English DT Article ID BREAST-CANCER; AROMATASE-ACTIVITY; NURSES HEALTH; MELATONIN; OBESITY; CELLS; WOMEN; POPULATION; HORMONES; GROWTH AB Melatonin has several oncostatic properties, including possible anti-estrogenic and anti-aromatase activity, and seems to be linked with fat metabolism. Night workers have lower levels of melatonin, which may predispose them to develop cancer. Endometrial cancer risk is influenced significantly by hormonal and metabolic factors; therefore, we hypothesize that night workers may have an increased risk of endometrial cancer. Of the 121,701 women enrolled in a prospective cohort study, 53,487 women provided data on rotating night shift work in 1988 and were followed through on June 1, 2004. A total of 515 women developed medical record-confirmed invasive endometrial cancer. We used Cox regression models to calculate multivariate relative risks (MVRRs), controlling for endometrial cancer risk factors. Women who worked 20+ years of rotating night shifts had a significantly increased risk of endometrial cancer [MVRR, 1.47; 95% confidence interval (95% CI), 1.03-1.14]. In stratified analyses, obese women working rotating night shifts doubled their baseline risk of endometrial cancer (MVRR, 2.09; 95% CI, 1.24-3.52) compared with obese women who did no night work, whereas a nonsignificant increase was seen among non-obese women (MVRR, 1.07; 95% CI, 0.60-1.92). Women working rotating night shifts for a long duration have a significantly increased risk of endometrial cancer, particularly if they are obese. We speculate that this increased risk is attributable to the effects of melatonin on hormonal and metabolic factors. Our results add to growing literature that suggests women who work at night may benefit from cancer prevention strategies. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. KFJ Spital, Ludwig Boltzmann Inst Appl Canc, Vienna, Austria. Appl Canc Res Inst Translat Res Vienna, Vienna, Austria. RP Viswanathan, AN (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, 75 Francis St L2, Boston, MA 02115 USA. EM aviswanathan@lroc.harvard.edu FU NCI NIH HHS [1K07 CA117979-01] NR 29 TC 136 Z9 148 U1 4 U2 12 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 2007 VL 67 IS 21 BP 10618 EP 10622 DI 10.1158/0008-5472.CAN-07-2485 PG 5 WC Oncology SC Oncology GA 228AV UT WOS:000250700200062 PM 17975006 ER PT J AU Abrams, AN Hazen, EP Penson, RT AF Abrams, Annah N. Hazen, Eric P. Penson, Richard T. TI Psychosocial issues in adolescents with cancer SO CANCER TREATMENT REVIEWS LA English DT Review DE adotescent; cancer; psychological adjustment; psychosocial issues; development; quality of life ID NEWLY-DIAGNOSED CANCER; CHILDHOOD-CANCER; PEDIATRIC CANCER; LYMPHOBLASTIC-LEUKEMIA; SOCIAL INTERACTIONS; TEACHER RATINGS; ADULT SURVIVORS; CLINICAL-TRIALS; SPERM BANKING; YOUNG-ADULTS AB Cancer in adolescents is uncommon and when it occurs raises a number of unique challenges for both the patient and their families. Adolescence is a period of time of significant physical and emotional changes and a diagnosis of cancer during this time has a major impact on their psychological and physical development. In this review we will took at the psychosocial. issues facing adolescents who have cancer. We will address adolescent development, issues related to informed consent and assent, initial responses to the diagnosis of cancer, quality of life and the experience of the adolescent with cancer, psychological adjustment, support systems, body image issues, sexuality, education, hope, and treatment compliance. (c) 2007 Elsevier Ltd. All rights reserved. C1 Massachusetts Gen Hosp, Dept Child Psychiat & Pediat Hematol Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Child Psychiat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Hematol Oncol, Dept Med, Boston, MA 02114 USA. RP Abrams, AN (reprint author), Child & Adolescent Psychiat Pediat Hematol Oncol, 55 Fruit St,YAWKEY 8B, Boston, MA 02114 USA. EM aabrams@partners.org NR 87 TC 85 Z9 86 U1 4 U2 22 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0305-7372 J9 CANCER TREAT REV JI Cancer Treat. Rev. PD NOV PY 2007 VL 33 IS 7 BP 622 EP 630 DI 10.1016/j.ctrv.2006.12.006 PG 9 WC Oncology SC Oncology GA 234LG UT WOS:000251165000006 PM 17434265 ER PT J AU Cesario, DA Turner, JW William, G AF Cesario, David A. Turner, Jonathan W. William, G. TI Biventricular pacing and defibrillator use in chronic heart failure SO CARDIOLOGY CLINICS LA English DT Article ID CARDIAC-RESYNCHRONIZATION THERAPY; IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR; NONISCHEMIC DILATED CARDIOMYOPATHY; INTRAVENTRICULAR-CONDUCTION DELAY; LEFT-VENTRICULAR DYSFUNCTION; ACUTE MYOCARDIAL-INFARCTION; LONG-TERM SURVIVAL; SUDDEN-DEATH; RANDOMIZED-TRIAL; PROPHYLACTIC USE AB Since the 1970s when the implantable cardioverter defibrillator (ICD) was developed, multiple clinical trials have documented survival benefits in certain high-risk subsets of heart failure patients. Over the past decade, cardiac resynchronization therapy (CRT) emerged as an important therapy in carefully selected patients with ongoing symptoms despite optimized pharmacological therapy. ICDs should be considered first-line therapy for survivors of life-threatening ventricular arrhythmic events. Subsets of patients with both ischemic and nonischemic dilated cardiomyopathy appear to have a survival benefit from primary ICD therapy. CRT has resulted in substantial symptomatic improvement and survival benefits in a subgroup of chronic heart failure patients. CRT should be considered in heart failure patients undergoing ICD implantation who have evidence of ventricular dyssynchrony. C1 [William, G.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Cesario, David A.; Turner, Jonathan W.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. RP William, G (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM gdec@partners.org NR 57 TC 3 Z9 3 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0733-8651 J9 CARDIOL CLIN JI Cardiol. Clin. PD NOV PY 2007 VL 25 IS 4 BP 595 EP + DI 10.1016/j.ccl.2007.09.002 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 247CK UT WOS:000252054500012 PM 18063163 ER PT J AU Cizek, SM Bedri, S Talusan, P Silva, N Lee, H Stone, JR AF Cizek, Stephanie M. Bedri, Shahinaz Talusan, Paul Silva, Nilsa Lee, Hang Stone, James R. TI Risk factors for atherosclerosis and the development of preatherosclerotic intimal hyperplasia SO CARDIOVASCULAR PATHOLOGY LA English DT Article DE intimal hyperplasia; intimal thickening; intima; atherosclerosis; smoking; hypertension; body mass index; age; diabetes ID INTERNAL THORACIC ARTERIES; AMERICAN-HEART-ASSOCIATION; CORONARY-ARTERIES; VASCULAR-LESIONS; MAMMARY ARTERY; BYPASS GRAFTS; ARTERIOSCLEROSIS; DEFINITION; PATHOLOGY; COMMITTEE AB Background: Intimal hyperplasia or thickening is considered to be the precursor lesion for atherosclerosis in humans; however, the factors governing its formation are unclear. To gain insight into the etiology of preatherosclerotic intimal hyperplasia, we correlated traditional risk factors for atherosclerosis with the intimal hyperplasia in an atherosclerosis-resistant vessel, the internal thoracic artery. Methods: Paired internal thoracic arteries were obtained from 89 autopsies. Multivariate logistic regression and multiple regression models were used to examine the association of preatherosclerotic, intimal hyperplasia with traditional risk factors for atherosclerosis: age, gender, hypertension, smoking, body mass index, diabetes, and hypercholesterolemia. Results: Atherosclerotic lesions consisting of fatty streaks and/or type III intermediate lesions were identified in 19 autopsies. Only age > 75 years was found to be significantly correlated with atherosclerotic lesion development (P=.01). Multiple regression model of the intima/media ratio in all 89 cases revealed age > 75 years (P <.0001), age 51-75 years (P=.0012), smoking (P=.008), and hypertension (P=.02) to be significantly correlated with intimal thickness. In the 70 cases without atherosclerosis, only age 51-75 years (P=.006) and smoking (P=.028) were found to be significantly associated with preatherosclerotic intimal thickening. Conclusions: In the atherosclerosis-resistant internal thoracic artery, preatherosclerotic intimal hyperplasia routinely forms during adulthood after the fourth decade and is associated with at least two traditional risk factors for atherosclerosis: age and smoking. These observations indicate that in some settings, intimal hyperplasia may be part of the disease process of atherosclerosis and that its fort-nation may be influenced by traditional risk factors for atherosclerosis. (c) 2007 Elsevier Inc. All rights reserved. C1 Massachusetts Gen Hosp, Harvard Med Sch, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Harvard Med Sch, Ctr Biostat, Boston, MA 02114 USA. RP Stone, JR (reprint author), Massachusetts Gen Hosp, Harvard Med Sch, Dept Pathol, Boston, MA 02114 USA. EM jrstone@partners.org FU NHLBI NIH HHS [R01 HL074324, R01 HL074324-03, R01 HL074324-04] NR 22 TC 24 Z9 25 U1 0 U2 12 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 2007 VL 16 IS 6 BP 344 EP 350 DI 10.1016/j.carpath.2007.05.007 PG 7 WC Cardiac & Cardiovascular Systems; Pathology SC Cardiovascular System & Cardiology; Pathology GA 235BX UT WOS:000251209600004 PM 18005873 ER PT J AU Lee, HJ Sakamoto, H Luo, H Skaznik-Wikiel, ME Friel, AM Niikura, T Tilly, JC Niikura, Y Klein, R Styer, AK Zukerberg, LR Tilly, JL Rueda, BR AF Lee, Ho-Joon Sakamoto, Hideo Luo, Hongwei Skaznik-Wikiel, Malgorzata E. Friel, Anne M. Niikura, Teruko Tilly, Jacqueline C. Niikura, Yuichi Klein, Rachael Styer, Aaron K. Zukerberg, Lawrence R. Tilly, Jonathan L. Rueda, Bo. R. TI Loss of CABLES1, a cyclin-dependent kinase-interacting protein that inhibits cell cycle progression, results in germline expansion at the expense of oocyte quality in adult female mice SO CELL CYCLE LA English DT Article DE cell cycle; INK4a; Cables; germ cell; stem cell; oogenesis; oocyte; ovary ID STEM-CELLS; EGGS FOREVER; BONE-MARROW; MOUSE OVARY; EXPRESSION; OVOGENESIS; FOLLICLES; FAILURE; GROWTH; WEE1 AB Recent studies have shown that cell cycle inhibitors encoded by the Ink4a gene locus constrain the self-renewing activity of adult stem cells of the hematopoietic and nervous systems. Here we report that knockout (KO) of the Cables1 [cyclin-dependent kinase (CDK)-5 and ABL enzyme substrate 1] cell cycle-regulatory gene in mice has minimal to no effect on hematopoietic stem cell (HSC) dynamics. However, female Cables1-null mice exhibit a significant expansion of germ cell (oocyte) numbers throughout adulthood. This is accompanied by a dramatic elevation in the number of atretic immature oocytes within the ovaries and an increase in the incidence of degenerating oocytes retrieved following superovulation of CABLES1-deficient females. These outcomes are not observed in mice lacking p16INK4a alone or both p16INK4a and p19ARF. These data support recent reports that adult female mice can generate new oocytes and follicles but the enhancement of postnatal oogenesis by Cables1 KO appears offset by a reduction in oocyte quality, as reflected by increased elimination of these additional germ cells via apoptosis. This work also reveals cell lineage specificity with respect to the role that specific CDK-interacting proteins play in restraining the activity of adult germline versus somatic stem cells. C1 [Lee, Ho-Joon; Sakamoto, Hideo; Luo, Hongwei; Skaznik-Wikiel, Malgorzata E.; Friel, Anne M.; Niikura, Teruko; Tilly, Jacqueline C.; Niikura, Yuichi; Styer, Aaron K.; Tilly, Jonathan L.; Rueda, Bo. R.] Massachusetts Gen Hosp, Vincent Ctr Reprod Biol, Vincent Obstetr & Gynecol Serv, Boston, MA USA. [Klein, Rachael] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA USA. [Zukerberg, Lawrence R.] Massachusetts Gen Hosp, Harvard Med Sch, Dept Pathol, Boston, MA USA. RP Rueda, BR (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM brueda@partners.org FU NCI NIH HHS [R01-CA098333]; NIA NIH HHS [R01-AG024999] NR 30 TC 16 Z9 18 U1 0 U2 3 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD NOV 1 PY 2007 VL 6 IS 21 BP 2678 EP 2684 PG 7 WC Cell Biology SC Cell Biology GA 240VB UT WOS:000251615200016 PM 17912041 ER PT J AU Veiga, E Guttman, JA Bonazzi, M Boucrot, E Toledo-Arana, A Lin, AE Enninga, J Pizarro-Cerda, J Finlay, BB Kirchhausen, T Cossart, P AF Veiga, Esteban Guttman, Julian A. Bonazzi, Matteo Boucrot, Emmanuel Toledo-Arana, Alejandro Lin, Ann E. Enninga, Jost Pizarro-Cerda, Javier Finlay, B. Brett Kirchhausen, Tomas Cossart, Pascale TI Invasive and adherent bacterial pathogens co-opt host clathrin for infection SO CELL HOST & MICROBE LA English DT Article ID GROWTH-FACTOR RECEPTOR; COATED PITS; MAMMALIAN-CELLS; LISTERIA-MONOCYTOGENES; MEDIATED ENDOCYTOSIS; EGF RECEPTORS; PROTEIN; MEMBRANE; DYNAMIN; ENTRY AB Infection by the bacterium Listeria monocytogenes depends on host cell clathrin. To determine whether this requirement is widespread, we analyzed infection models using diverse bacteria. We demonstrated that bacteria that enter cells following binding to cellular receptors (termed "zippering" bacteria) invade in a clathrin-dependent manner. In contrast, bacteria that inject effector proteins into host cells in order to gain entry (termed "triggering" bacteria) invade in a clathrin-independent manner. Strikingly, enteropathogenic Escherichia coli (EPEC) required clathrin to form actin-rich pedestals in host cells beneath adhering bacteria, even though this pathogen remains extracellular. Furthermore, clathrin accumulation preceded the actin rearrangements necessary for Listeria entry. These data provide evidence for a clathrin-based entry pathway allowing internalization of large objects (bacteria and ligand-coated beads) and used by "zippering" bacteria as part of a general mechanism to invade host mammalian cells. We also revealed a nonendocytic role for clathrin required for extracellular EPEC infections. C1 Inst Pasteur, Unite Interact Bacteries Cellules, F-75015 Paris, France. INSERM, U604, F-75015 Paris, France. INSERM, USC2020, F-75015 Paris, France. Univ British Columbia, Michael Smith Labs, Vancouver, BC V6T 1Z4, Canada. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. Inst Pasteur, Unite Pathogenie Microbienne Mol, F-75015 Paris, France. INSERM, U786, F-75015 Paris, France. RP Veiga, E (reprint author), Inst Pasteur, Unite Interact Bacteries Cellules, F-75015 Paris, France. EM eveiga@pasteur.fr; pcossart@pasteur.fr RI veiga, esteban/C-2129-2011; Toledo-Arana, Alejandro/F-9624-2011; Bonazzi, Matteo/G-1623-2011 OI veiga, esteban/0000-0002-7333-2466; Toledo-Arana, Alejandro/0000-0001-8148-6281; Bonazzi, Matteo/0000-0001-5499-8759 FU NIAID NIH HHS [U54 AI057159, U54 AI057159-010008]; NIGMS NIH HHS [R01 GM075252]; PHS HHS [US4 A1057159-05] NR 55 TC 127 Z9 129 U1 1 U2 6 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1931-3128 J9 CELL HOST MICROBE JI Cell Host Microbe PD NOV PY 2007 VL 2 IS 5 BP 340 EP 351 DI 10.1016/j.chom.2007.10.001 PG 12 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 233XT UT WOS:000251124300011 PM 18005755 ER PT J AU Van Dyck, F Braem, CV Chen, Z Declercq, J Deckers, R Kim, BM Ito, S Wu, MK Cohen, DE Dewerchin, M Derua, R Waelkens, E Fiette, L Roebroek, A Schuit, F Van de Ven, WJM Shivdasani, RA AF Van Dyck, Frederik Braem, Caroline V. Chen, Zhao Declercq, Jeroen Deckers, Rob Kim, Byeong-Moo Ito, Susumu Wu, Michele K. Cohen, David E. Dewerchin, Mieke Derua, Rita Waelkens, Etienne Fiette, Laurence Roebroek, Anton Schuit, Frans Van de Ven, Wim J. M. Shivdasani, Ramesh A. TI Loss of the PlagL2 transcription factor affects lacteal uptake of chylomicrons SO CELL METABOLISM LA English DT Article ID INTRACELLULAR-TRANSPORT; GENE-EXPRESSION; MICE; ACTIVATION; INTESTINE; DISRUPTION; ABSORPTION; FAMILY; MODEL AB Enterocytes assemble dietary lipids into chylomicron particles that are taken up by intestinal lacteal vessels and peripheral tissues. Although chylomicrons are known to assemble in part within membrane secretory pathways, the modifications required for efficient vascular uptake are unknown. Here we report that the transcription factor pleomorphic adenoma gene-like 2 (PlagL2) is essential for this aspect of dietary lipid metabolism. PlagL2(-/-) mice die from postnatal wasting owing to failure of fat absorption. Lipids modified in the absence of PlagL2 exit from enterocytes but fail to enter interstitial lacteal vessels. Dysregulation of enterocyte genes closely linked to intracellular membrane transport identified candidate regulators of critical steps in chylomicron assembly. PlagL2 thus regulates important aspects of dietary lipid absorption, and the PlagL2(-/-) animal model has implications for the amelioration of obesity and the metabolic syndrome. C1 Katholieke Univ Leuven, Oncol Mol Lab, Dept Human Genet, B-3000 Louvain, Belgium. Katholieke Univ Leuven, Ctr Transgene Technol & Gene Therapy, B-3000 Louvain, Belgium. Katholieke Univ Leuven, Lab Expt Mouse Genet, Dept Human Genet, B-3000 Louvain, Belgium. Katholieke Univ Leuven, Gene Express Unit, Div Biochem, B-3000 Louvain, Belgium. Katholieke Univ Leuven, Lab Prot Phosphorylat & Proteom, B-3000 Louvain, Belgium. Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Brigham & Womens Hosp, Boston, MA 02115 USA. CMU, CH-1211 Geneva 4, Switzerland. RP Van de Ven, WJM (reprint author), Katholieke Univ Leuven, Oncol Mol Lab, Dept Human Genet, B-3000 Louvain, Belgium. EM wim.vandeven@med.kuleuven.be FU NIDDK NIH HHS [R01 DK56626, R01 DK61139, R01 DK48873] NR 27 TC 15 Z9 15 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1550-4131 J9 CELL METAB JI Cell Metab. PD NOV PY 2007 VL 6 IS 5 BP 406 EP 413 DI 10.1016/j.cmet.2007.09.010 PG 8 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 229NC UT WOS:000250809700011 PM 17983586 ER PT J AU Chen, BZ Zhou, XF Taghizadeh, K Chen, JY Stubbe, J Dedon, PC AF Chen, Bingzi Zhou, Xinfeng Taghizadeh, Koh Chen, Jingyang Stubbe, JoAnne Dedon, Peter C. TI GC/MS methods to quantify the 2-deoxypentos-4-ulose and 3 '-phosphoglycolate pathways of 4 ' oxidation of 2-deoxyribose in DNA: application to DNA damage produced by gamma radiation and bleomycin SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID CAPTURE MASS-SPECTROMETRY; STRAND BREAKS; GAS-CHROMATOGRAPHY; AQUEOUS-SOLUTION; REACTIVE METABOLITE; SUGAR RELEASE; ABASIC SITES; OXIDIZED DNA; BASE DAMAGE; NEOCARZINOSTATIN AB DNA oxidation plays a substantive role in the pathophysiology of human diseases, such as cancer. While the chemistry of nucleobase lesions has dominated studies of DNA damage, there is growing evidence that the oxidation of 2-deoxyribose in DNA plays a critical role in the genetic toxicology of oxidative stress. As part of an effort to define the spectrum of 2-deoxyribose oxidation products arising in vitro and in vivo, we now describe methods for quantifying products arising from 4' oxidation of 2-deoxyribose in DNA. The chemistry of 4' oxidation partitions between either of two pathways to form either a 2-deoxypentos-4-ulose abasic site (oxAB) or a strand break comprised of a 3'-phosphoglycolate (3PG) residue and a 5'-phosphate, with the release of either malondialdehyde and free base or a base propenal. Highly sensitive gas chromatography/mass spectrometry (GUMS) methods were developed to quantify both lesions. The abasic site was converted to a 3'-phosphoro-3-pyridazinylmethylate derivative by treatment of the damaged DNA with hydrazine, which was released from DNA as 3-hydroxymethylpyridazine (HMP) by enzymatic hydrolysis. Similarly, 3PG was released as 2-phosphoglycolic acid (PG) by enzymatic hydrolysis. Following HPLC prepurification, both PG and HMP were silylated and quantified by GUMS, with limits of detection of 100 and 200 fmol and sensitivities of 2 and 4 lesions per 106 nucleotides (m) in 250 mu g of DNA, respectively. Following validation of the methods with oligodeoxynucleotides containing the two lesions, the methods were applied to DNA damage produced by bleomycin and gamma radiation. As expected for an agent known to produce only 4' oxidation of DNA, the quantities of 3PG and oxAB accounted for all 2-deoxyribose oxidation events, as indicated by slopes of 0.8 and 0.3, respectively, in plots of the lesion frequency against total 2-deoxyribose oxidation events, with the latter determined a plasmid-nicking assay. 3PG residues and oxAB were produced at the rate of 32 and 12 lesions per 10 nt per mu M, respectively. For gamma radiation, on the other hand, 4' oxidation was found to comprise only 13% of 2-deoxyribose oxidation chemistry, with 3% oxAB (4 per 106 nt per Gy) and 10% 3PG (13 per 106 nt per Gy). C1 MIT, Dept Biol Engn, Cambridge, MA 02139 USA. MIT, Ctr Environm Hlth Sci, Cambridge, MA 02139 USA. MIT, Dept Chem, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP Dedon, PC (reprint author), MIT, Dept Biol Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM pcdedon@mit.edu OI Dedon, Peter/0000-0003-0011-3067 FU NCI NIH HHS [CA26735, P01 CA026731, P01 CA026731-26, R01 CA103146, R01 CA103146-04]; NIEHS NIH HHS [ES002109, P30 ES002109] NR 59 TC 16 Z9 17 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD NOV PY 2007 VL 20 IS 11 BP 1701 EP 1708 DI 10.1021/tx700164y PG 8 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 233KP UT WOS:000251090100016 PM 17944541 ER PT J AU Shepherd, J Hilderbrand, SA Waterman, P Heinecke, JW Weissleder, R Libby, P AF Shepherd, Joanna Hilderbrand, Scott A. Waterman, Peter Heinecke, Jay W. Weissleder, Ralph Libby, Peter TI A fluorescent probe for the detection of myeloperoxidase activity in atherosclerosis-associated macrophages SO CHEMISTRY & BIOLOGY LA English DT Article ID LOW-DENSITY-LIPOPROTEIN; APOLIPOPROTEIN-A-I; HYPOCHLORITE-MODIFIED PROTEINS; ACUTE CORONARY SYNDROMES; OXIDATIVE STRESS; SYNOVIAL-FLUID; HUMAN NEUTROPHILS; T-LYMPHOCYTES; OXIDIZED LDL; LUNG INJURY AB The myeloperoxidase (MPO)-derived oxidant hypochlorous acid (HOCI/OCI-) is implicated in the pathogenesis of atherosclerosis and other inflammatory states. We have synthesized an imaging probe, sulfonaphthoamino-phenyl fluorescein (SNAPF), that selectively reacts with HOCI. SNAPF detects HOCI produced by stimulated MPO-expressing cells cultured from human whole blood, as well as HOCI from bone marrow (BM)-derived macrophages isolated from transgenic mice that express human MPO. Two lines of evidence indicate that SNAPF permits the in vivo imaging of HOCI production. First, we used this approach to demonstrate HOCI production by neutrophils in experimental murine peritonitis. Second, we detected HOCI production by MPO expressing cells in human atherosclerotic arteries. Thus, fluorescence reflectance imaging by SNAPF may provide a valuable noninvasive molecular imaging tool for implicating HOCI and MPO in the damage of inflamed tissues. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Cardiovasc,Dept Med, Boston, MA 02215 USA. Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Univ Washington, Dept Med, Seattle, WA 98195 USA. RP Libby, P (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Cardiovasc,Dept Med, Boston, MA 02215 USA. EM plibby@rics.bwh.harvard.edu FU NHLBI NIH HHS [U01 HL080731, U01 HL080731-01, UO1 HL080731] NR 44 TC 129 Z9 131 U1 4 U2 38 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-5521 J9 CHEM BIOL JI Chem. Biol. PD NOV PY 2007 VL 14 IS 11 BP 1221 EP 1231 DI 10.1016/j.chembiol.2007.10.005 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 236JK UT WOS:000251299000006 PM 18022561 ER PT J AU Pomati, F Cotsapas, CJ Castiglioni, S Zuccato, E Calamari, D AF Pomati, Francesco Cotsapas, Chris J. Castiglioni, Sara Zuccato, Ettore Calamari, Davide TI Gene expression profiles in zebrafish (Danio rerio) liver cells exposed to a mixture of pharmaceuticals at environmentally relevant concentrations SO CHEMOSPHERE LA English DT Article DE pharmaceuticals; liver cells; environment; zebrafish; growth; gene expression ID THERAPEUTIC DRUGS; IN-VIVO; TUMORIGENESIS; NORMALIZATION; METABOLISM; APOPTOSIS; PATHWAYS; RESIDUES; REMOVAL; COMPLEX AB The effects of a mixture of pharmaceuticals at environmentally relevant concentrations were studied on growth and transcriptional regulation in zebrafish liver (ZFL) cells. The mixture of 13 ingredients was assembled to mimic the association and low concentration (ng/l) of drugs as detected in the environment, and decidedly inhibited ZFL cells proliferation in vitro over a 72 h exposure time. Using an oligonucleotide DNA-microarray targeting 14000 zebrafish transcripts, we profiled gene expression in ZFL cells treated with ecologically relevant levels of the drug mixture. Compared to unexposed controls, ZFL cells challenged with pharmaceuticals were characterised by transcriptional repression involving primary metabolism and regulation of the cell cycle. On the other hand, we observed upregulation of genes identifying protein kinase signalling pathways and DNA-repair mechanisms. Part of the identified transcripts could be associated with general toxicity, while others were possibly linked to the effects of specific pharmaceuticals. Drugs also caused overexpression of oestrogen receptor beta and the oestrogen responsive protein GREB1 The context drawn by our data highlights a similarity in the response to the drug mixture in fish and previously employed human cells, and further prioritise studies targeting the potential risks associated with the presence of pharmaceuticals in the environment. (C) 2007 Elsevier Ltd. All rights reserved. C1 Univ New S Wales, Sch Biotechnol & Biomol Sci, Sydney, NSW 2052, Australia. Massachusetts Gen Hosp, Ctr Human Genet Res, CPZN 6818, Boston, MA 02114 USA. Mario Negri Inst Pharmacol Res, Dept Environm Hlth Sci, I-20157 Milan, Italy. Univ Insubria, Dept Biotechnol & Mol Sci, I-21100 Varese, Italy. RP Pomati, F (reprint author), Univ New S Wales, Sch Biotechnol & Biomol Sci, Sydney, NSW 2052, Australia. EM f.pomati@unsw.edu.au OI Cotsapas, Chris/0000-0002-7772-5910 NR 35 TC 31 Z9 32 U1 1 U2 21 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0045-6535 J9 CHEMOSPHERE JI Chemosphere PD NOV PY 2007 VL 70 IS 1 BP 65 EP 73 DI 10.1016/j.chemosphere.2007.07.048 PG 9 WC Environmental Sciences SC Environmental Sciences & Ecology GA 237XD UT WOS:000251408800008 PM 17764721 ER PT J AU Shields, AE AF Shields, Alexandra E. TI Trends in private insurance, Medicaid/State Children's Health Insurance Program, and the health-care safety net - Implications for asthma disparities SO CHEST LA English DT Article DE asthma; disparities; health policy; Medicare; private insurance; uninsured ID INFORMATION-TECHNOLOGY; INCENTIVES; MANAGEMENT; COVERAGE; QUALITY; CENTERS; DISEASE AB Disparities in asthma prevalence, severity, quality of care, and outcomes have been widely documented across racial/ethnic communities, among privately insured vs publicly insured patients, and according to patients' socioeconomic status, among other patient characteristics. In order to effectively address asthma disparities, changes will need to be made across all systems of care in which these subpopulations receive health-care services. The majority of current trends in private insurance, Medicaid/State Children's Health Insurance Program, and the safety net are likely to further exacerbate asthma disparities rather than help to reduce these disparities. Asthma cannot be effectively managed unless individuals have affordable access to a full range of services and receive coordinated, quality health care. Multiple policy levers will need to be simultaneously employed to ensure access to the full range of services needed for effective asthma management, especially among low-income and minority persons with asthma in order to reduce the gap in disparities. The needs of these patients must be thoughtfully addressed and strategically advocated for within all systems of care in which these subpopulations receive health services. This overall strategy must necessarily include consideration of the capacity of safety-net providers to meet the needs of uninsured and underinsured persons with asthma. This article reviews trends in health-care financing, in clinical management, and the health-care safety net, and assesses their likely impact on asthma disparities. It concludes with a discussion of key policy arenas that will have significant influence on the eventual success of efforts to reduce asthma disparities. C1 Harvard Univ, Inst Hlth Policy, Harvard Med Sch, Partner Hlthcare, Boston, MA 02114 USA. RP Shields, AE (reprint author), Massachusetts Gen Hosp, Inst Hlth Policy, Partner Hlthcare, 50 Stanford St,9th Flr,Suite 901, Boston, MA 02114 USA. EM ashields@partners.org NR 55 TC 14 Z9 14 U1 2 U2 4 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 2007 VL 132 IS 5 SU S BP 818S EP 830S DI 10.1378/chest.07-1903 PG 13 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 235MV UT WOS:000251239300009 PM 17998346 ER PT J AU Alimenoff, P Sales, A Rounds, S Miller, M Schroeder, K Lentz, K Perlin, J AF Alimenoff, Peter Sales, Anne Rounds, Sharon Miller, Michael Schroeder, Kelly Lentz, Karen Perlin, Jonathan TI Intensive care services in the veterans health administration SO CHEST LA English DT Article DE critical care; hospitals; veterans; organization and administration ID UNITED-STATES 1985-2000; PROFESSIONAL SOCIETIES; DESCRIPTIVE ANALYSIS; CRITICALLY ILL; COMPLICATIONS; MEDICINE; CRISIS; RECOMMENDATIONS; POPULATION; GUIDELINES AB Objective: We describe the national organization and distribution of intensive care services within the Veterans Health Administration (VHA), the largest single integrated health-care system in the United States. Data Sources: Data come primarily from the 2004 Survey of Intensive Care Units in VHA, an electronically distributed survey of all ICUs in the VHA. Medical directors and nurse managers from all 213 ICUs in the VHA responded to the survey. In addition, we extracted data on the number of ICU admissions and unique veterans served from national VHA databases. Results: The VHA has a geographically dispersed, multilevel system of care with variation in geographic access for eligible veterans (varying from 3.1 to 3.5 ICU beds per 1,000 patient discharges) and variation in service provision (from 10 to 19 level 1 ICUs across four regions). Level I ICUs are the highest tertiary-level ICUs, with the full range of subspecialty care. The proportion of beds associated with VHA-developed ICU levels of care ranges from 55% level I beds in the Northeast to 73% in the South, while level 4 beds represent 4% of all ICU beds in the South and 10% in the Midwest. Conclusions: Overall, the VHA system has a fair amount of regional variation, but level 1 ICUs are available in all geographic regions, and there are regional clusters of all levels. Adopting a four-level system for rating ICUs may assist in monitoring and assessing the quality of care provided in the smallest, most rural facilities. C1 Univ Alberta, Edmonton, AB T6G 3G2, Canada. VA Heartland Network, Kansas City, MO USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. Prov VAMC, Providence, RI USA. VISN 1, Boston, MA USA. St Louis VA Med Ctr, St Louis, MO USA. VA Hlthcare Anal & Informat Grp, Milwaukee, WI USA. Dept Vet Affairs, Washington, DC USA. RP Sales, A (reprint author), Univ Alberta, 3-114 Clin Sci Bldg, Edmonton, AB T6G 3G2, Canada. EM anne.sales@ualberta.ca OI Sales, Anne/0000-0001-9360-3334 NR 35 TC 0 Z9 0 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD NOV PY 2007 VL 132 IS 5 BP 1455 EP 1462 DI 10.1378/chest.06-3083 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 231TU UT WOS:000250972700010 ER PT J AU Lee-Lewandrowski, E Januzzi, JL Green, SM Tannous, B Wu, AHB Smith, A Wong, A Murakami, MM Kaczmarek, J Apple, FS Miller, WL Hartman, K Jaffe, AS AF Lee-Lewandrowski, Elizabeth Januzzi, James L. Green, Sandy M. Tannous, Bakhos Wu, Alan H. B. Smith, Andrew Wong, Alicia Murakami, MaryAnn M. Kaczmarek, Jason Apple, Fred S. Miller, Wayne L. Hartman, Karen Jaffe, Allan S. TI Multi-center validation of the response biomedical corporation RAMP (R) NT-proBNP assay with comparison to the Roche diagnostics GmbH Elecsys (R) proBNP assay SO CLINICA CHIMICA ACTA LA English DT Article DE NT-proBNP; point-of-care; RAMP (R); biomedical; heart failure; method validation ID BRAIN NATRIURETIC PEPTIDE; HEART-FAILURE; MORTALITY AB Background: NT-proBNP measurements aid in the evaluation of patients with suspected heart failure (HF) and may facilitate risk stratification inpatients with HF and acute coronary syndrome (ACS). Point-of-care (POC) assays may provide more timely results and potentially improve patient outcomes. Methods: We evaluated the analytical performance of the Response Biomedical Corporation whole blood RAMP amino-terminal pro-B type natriuretic peptide (NT-proBNP) POC assay compared to the Roche Elecsys proBNP (NT-proBNP) assay. Results: Intra-day and total imprecision (% CV) ranged from 5.5% to 10.3% at 140, 449 and 1675 ng/L. The lowest concentration that yields a 20% CV was 57 ng/L. The lower limit of detection was 18 ng/L. The upper limit of linearity was validated to 23,428 ng/L with an average recovery of 95%. Correlation by Passing and Bablok regression yielded RAMP = 1.01 Elecsys + 14.6, r = 0.98 (n = 540; range of Elecsys values < 5 to >35,000). Concordance of RAMP versus Elecsys using cut-offs of 125 ng/L for subjects < 75 years and 450 ng/L for subjects >= 75 was 92% (95% CI 89-94%) for a group consisting of 127 apparently healthy individuals and 208 non-healthy subjects without HE, and 99% (95% CI 97-100%) for patients with HF, using the New York Heart Association (NYHA) functional classification. Overall, 80%, 87%, 97% and 100% of the RAMP results and 77%, 85%, 96% and 100% of the Elecsys results were greater than the age appropriate cut-off for NYHA I, II, III or IV groups. For both the RAMP and Elecsys results, the median NT-proBNP value was statistically correlated (increasing) with NYHA I, II, III or IV groups, respectively (p < 0.0001), with no significant difference between the two methods. Conclusions: The POC Response Biomedical RAMP NT-proBNP assay provides comparable results that measured on the FDA cleared Roche Elecsys central laboratory platform, (C) 2007 Elsevier B.V. All rights reserved. C1 Mayo Clin, Rochester, MN 55905 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. San Francisco Gen Hosp, San Francisco, CA 94110 USA. Hennepin Cty Med Ctr, Minneapolis, MN 55415 USA. RP Jaffe, AS (reprint author), Mayo Clin, Rochester, MN 55905 USA. EM jaffe.allan@mayo.edu NR 4 TC 9 Z9 11 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0009-8981 J9 CLIN CHIM ACTA JI Clin. Chim. Acta PD NOV-DEC PY 2007 VL 386 IS 1-2 BP 20 EP 24 DI 10.1016/j.cca.2007.07.015 PG 5 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 220ZJ UT WOS:000250195700004 PM 17854790 ER PT J AU Letko, E Gurcan, HM Papaliodis, GN Christen, W Foster, CS Ahmed, AR AF Letko, E. Guercan, H. M. Papaliodis, G. N. Christen, W. Foster, C. S. Ahmed, A. R. TI Relative risk for cancer in mucous membrane pemphigoid associated with antibodies to the beta 4 integrin subunit SO CLINICAL AND EXPERIMENTAL DERMATOLOGY LA English DT Article ID TERM-FOLLOW-UP; GASTRIC-CARCINOMA; INTRAVENOUS IMMUNOGLOBULIN; ANTIEPILIGRIN LAMININ-5; LUNG-CARCINOMA; EPILIGRIN; AUTOANTIBODIES; AUTOIMMUNE; INVASION; RECEPTOR AB Background Mucous membrane pemphigoid (MMP) is a mucocutaneous vesiculobullous autoimmune disease characterized by autoantibodies to components of the basement membrane zone (BMZ). Recently, it has been reported that patients with MMP who have autoantibodies to laminin 5, known as anti-epiligrin cicatricial pemphigoid (AECP) have a high incidence of malignancy. Objective The purpose of this study was to determine the association between malignancy and MMP in patients with antibodies to beta 4 integrin. Methods The incidence of cancer was studied in 79 patients with MMP and/or ocular cicatricial pemphigoid (OCP) who had antibodies to human beta 4 integrin subunit. In each patient, the diagnosis was made by histology and confirmed by immunopathology of affected tissues. It was compared to the expected incidence, for age- and gender-matched individuals, in the National Cancer Institute's Surveillance, Epidemiology and End Results (NCISEER) database. Results Of 79 patients, 3 had cancer. The relative risk (RR) for cancer in patients with MMP and/or OCP, with autoantibodies to human beta 4 integrin subunit was 0.29 (95% CI 0.62-8.77). The expected number in the NCISEER database was 10.37. This difference was statistically significant (P < 0.01). Conclusions This incidence of cancer in MMP/OCP patients, with antibodies to human beta 4 integrin subunit is considerably lower than expected. Preliminary observations in this and other studies suggest that serological subsets of MMP, based on antigen reactivity, have a different clinical course, prognosis and associations with cancer. C1 New England Baptist Hosp, Ctr Blistering Dis, Boston, MA 02120 USA. Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Immunol & Uveitis Serv, Boston, MA USA. Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. RP Gurcan, HM (reprint author), New England Baptist Hosp, Ctr Blistering Dis, 70 Parker Hill Ave,Suite 208, Boston, MA 02120 USA. EM arahmedmd@msn.com NR 25 TC 8 Z9 8 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0307-6938 J9 CLIN EXP DERMATOL JI Clin. Exp. Dermatol. PD NOV PY 2007 VL 32 IS 6 BP 637 EP 641 DI 10.1111/j.1365-2230.2007.02463.x PG 5 WC Dermatology SC Dermatology GA 221UI UT WOS:000250252400003 PM 17524068 ER PT J AU Emejuaiwe, N Jones, AC Ibrahim, SA Kwoh, CK AF Emejuaiwe, N. Jones, A. C. Ibrahim, S. A. Kwoh, C. K. TI Disparities in joint replacement utilization: a quality of care issue SO CLINICAL AND EXPERIMENTAL RHEUMATOLOGY LA English DT Article DE quality of care; osteoarthritis; joint replacement; racial disparities ID TOTAL HIP-ARTHROPLASTY; TOTAL KNEE ARTHROPLASTY; SURGEON PROCEDURE VOLUME; UNITED-STATES; ETHNIC-DIFFERENCES; RHEUMATOID-ARTHRITIS; MEDICARE POPULATION; RACIAL DISPARITIES; FUNCTIONAL STATUS; INDICATOR SET AB Although total joint replacement is an effective treatment option for end-stage lower extremity osteoarthritis, racial disparities in joint replacement utilization have been well documented. These disparities may be due in part to patient-level factors such as willingness to consider joint replacement and worse expectations of joint replacement outcomes. In addition, African-Americans may have worse outcomes after total joint replacement and are more likely to have surgery performed by surgeons with lower volumes or in hospitals with lower volumes. All of these issues may be considered concerns with the quality of care delivered to African-Americans with osteoarthritis. C1 Univ Pittsburgh, Sch Med, Pittsburgh, PA 15261 USA. VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. RP Kwoh, CK (reprint author), Univ Pittsburgh, Sch Med, BST S702,3500 Terrace St, Pittsburgh, PA 15261 USA. EM kwoh@pitt.edu NR 71 TC 3 Z9 3 U1 2 U2 2 PU CLINICAL & EXPER RHEUMATOLOGY PI PISA PA VIA SANTA MARIA 31, 56126 PISA, ITALY SN 0392-856X J9 CLIN EXP RHEUMATOL JI Clin. Exp. Rheumatol. PD NOV-DEC PY 2007 VL 25 IS 6 SU 47 BP S44 EP S49 PG 6 WC Rheumatology SC Rheumatology GA 235QA UT WOS:000251248200009 ER PT J AU Wang, Z Dahiya, S Provencher, H Muir, B Carney, E Coser, K Shioda, T Ma, XJ Sgroi, DC AF Wang, Zuncai Dahiya, Sonika Provencher, Heather Muir, Beth Carney, Erin Coser, Kathryn Shioda, Toshi Ma, Xiao-Jun Sgroi, Dennis C. TI The prognostic biomarkers HOXB13, IL17BR, and CHDH are regulated by estrogen in breast cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID GENE-EXPRESSION PATTERNS; CYCLIN D1 EXPRESSION; ENDOCRINE THERAPY; RECEPTOR STATUS; TAMOXIFEN; CELLS; RATIO; ASSAY; CARCINOMAS; RECURRENCE AB Purpose: We previously identified three genes, HOXB13, IL17BR, and CHDH, that strongly predict clinical outcome in estrogen receptor (ER)-positive breast cancer patients receiving tamoxifen monotherapy. The biological mechanisms linking these genes to estrogen signaling and tamoxifen response in breast cancer remain to be determined. Experimental Design: In a consecutive series of 148 ER-positive and ER-negative breast cancers, HOXB13, IL17BR, and CHDH gene expression was measured by quantitative real-time PCR and correlated with ER, PR, and HER2 expression. The role of estrogen and ER in the regulation of these three genes was assessed in several ER-positive and ER-negative breast cancer cell lines. Results: In primary breast tumors, HOXB13 expression correlated negatively, and IL17BR and CHDH expression correlated positively, with ER status, and all three genes exhibited an ER-dependent correlation pattern with HER2 status that differs from PR and PS2, two canonical estrogen-regulated genes. Results using breast cancer cell lines show that these genes are regulated by estradiol in an ER-dependent manner, and that this regulation is abrogated by tamoxifen. Conclusions: HOXB13, IL17BR, and CHDH are estrogen-regulated genes, but their pattern of correlation with known positive (ER, PR) and negative (HER2) predictors of tamoxifen response differs from canonical ER signature genes. These results provide a biological rationale for the prognostic utility of these three genes in early-stage ER-positive breast cancer and for their potential to predict anti-estrogen resistance. C1 Massachusetts Gen Hosp E, Mol Pathol Res Unit, Harvard Univ, Sch Med,Dept Pathol, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Canc Res Ctr, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. AviaraDx, Carlsbad, CA USA. RP Sgroi, DC (reprint author), Massachusetts Gen Hosp E, Mol Pathol Res Unit, Harvard Univ, Sch Med,Dept Pathol, 149 13th St, Charlestown, MA 02129 USA. EM dsgroi@partners.org FU NCI NIH HHS [R01-1CA112021-01] NR 29 TC 42 Z9 45 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 2007 VL 13 IS 21 BP 6327 EP 6334 DI 10.1158/1078-0432.CCR-07-0310 PG 8 WC Oncology SC Oncology GA 229BZ UT WOS:000250777600011 PM 17975144 ER PT J AU Chabner, BA Ratain, MJ AF Chabner, Bruce A. Ratain, Mark J. TI Phase II trials published in 2002: a cross-specialty comparison showing significant design differences between oncology trials and other medical specialties (vol 13, pg 2400, 2007) SO CLINICAL CANCER RESEARCH LA English DT Correction C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Chicago, Dept Med, Chicago, IL 60637 USA. RP Chabner, BA (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 2 TC 2 Z9 2 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV 1 PY 2007 VL 13 IS 21 BP 6540 EP 6540 DI 10.1158/1078-0432.CCR-07-1108 PG 1 WC Oncology SC Oncology GA 229BZ UT WOS:000250777600036 PM 17975169 ER PT J AU Kramer, JR Giordano, TP El-Serag, HB AF Kramer, Jennifer R. Giordano, Thomas P. EL-Serag, Hashem B. TI Effect of human immunodeficiency virus and antiretrovirals on outcomes of hepatitis C: A systematic review from an epidemiologic perspective SO CLINICAL GASTROENTEROLOGY AND HEPATOLOGY LA English DT Article ID LIVER FIBROSIS PROGRESSION; HIV-INFECTED PATIENTS; HIV/HCV-COINFECTED PATIENTS; HEPATOCELLULAR-CARCINOMA; NATURAL-HISTORY; HEMOPHILIC PATIENTS; RISK-FACTORS; DRUG-USERS; DISEASE; IMPACT AB Background & Aims: We systematically reviewed the literature examining the association of human immunodeficiency virus (HIV) and antiretroviral therapy (ART) with liver disease in patients with hepatitis C virus (HCV) infection. Methods: PubMed was searched for studies examining hepatic fibrosis, cirrhosis, decompensated liver disease, hepatocellular carcinoma, and liver-related death. Thirty-nine reports (describing 34 unique studies) met inclusion criteria. Information was abstracted on study design, sampling frame, inclusion/exclusion criteria, sample size, results, and covariates used for adjustment. Because of the heterogeneity among study designs, a meta-analysis was not conducted. Results: Nine of the 12 cross-sectional studies showed a statistically significant association between HIV co-infection and fibrosis or cirrhosis, whereas 7 retrospective cohort studies were inconsistent. Six studies examined decompensated liver disease as the outcome: 5 of these found a significantly increased risk in patients with HIV co-infection. The 7 studies examining liver-related death showed a trend toward an association with HIV co-infection, although only 4 were statistically significant. Four studies examined the effect of HIV on hepatocellular carcinoma, 2 of which found no association. Of 10 studies that investigated the effect of ART on the risk of liver disease, half reported a significant protective association. Conclusions: HIV co-infection is associated with an increased risk of advanced liver disease in hepatitis C virus-infected patients. Data on hepatocellular carcinoma are sparse, but an association is plausible given the increased risk of advanced liver disease. In contrast, data for an effect of ART are plentiful, but findings are inconsistent. More robust studies are needed on this topic. C1 Michael E DeBakey Vet Affairs Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Houston, TX USA. Baylor Coll Med, Dept Med, Gastroenterol Sect, Houston, TX 77030 USA. Baylor Coll Med, Sect Hlth Serv Res, Houston, TX 77030 USA. Baylor Coll Med, Infect Dis Sect, Houston, TX 77030 USA. RP Kramer, JR (reprint author), 2002 Holcombe Blvd 152, Houston, TX 77030 USA. EM jkramer@bcm.tmc.edu FU NIDDK NIH HHS [K24DK078154-01]; NIMH NIH HHS [K23MH67505] NR 54 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1542-3565 J9 CLIN GASTROENTEROL H JI Clin. Gastroenterol. Hepatol. PD NOV PY 2007 VL 5 IS 11 BP 1321 EP 1328 DI 10.1016/j.cgh.2007.08.006 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 231KF UT WOS:000250944900016 PM 17981246 ER PT J AU McFarland, LV Clarridge, JE Beneda, HW Raugi, GJ AF McFarland, Lynne V. Clarridge, Jill E. Beneda, Henry W. Raugi, Gregory J. TI Fluoroquinolone use and risk factors for Clostridium difficile - Associated disease within a veterans administration health care system SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID DIARRHEA; ANTIBIOTICS; COMMUNITY; OUTBREAK AB Background. Prompted by the changing profile of Clostridium difficile infection and the impact of formulary policies in hospitals, we performed this study when an increase in the incidence of C. difficile - associated disease was noted at our health care center (Veterans Administration Puget Sound Health Care System, Seattle, Washington). Methods. A retrospective, matched case- control study of patients presenting to the Veterans Administration Puget Sound Health Care System, Seattle, Washington during 2004 was performed. Conditional logistic analysis determined risk factors for case patients, defined as individuals with diarrhea and test results ( i. e., culture or toxin assay results) positive for C. difficile, and control subjects, defined as individuals with diarrhea and test results negative for C. difficile. Results. C. difficile - associated disease incidence was 29.2 cases per 10,000 inpatient- days. The increase in the incidence of C. difficile - associated diarrhea that paralleled increased gatifloxacin use was not attributable to use of the antimicrobial but was a reflection of seasonal variation in the rate of C. difficile - associated disease. Multivariate analysis controlling for the time at which the assay was performed, the age of the patient, ward, and source of acquisition ( community- acquired vs. nosocomial disease) found 6 significant risk factors for C. difficile - associated diarrhea: receipt of clindamycin ( adjusted odds ratio [ aOR], 29.9; 95% confidence interval [ CI], 3.58 - 249.4), receipt of penicillin ( aOR, 4.1; 95% CI, 1.2 - 13.9), having a lower intestinal condition ( aOR, 2.8; 95% CI, 1.3-6.1), total number of antibiotics received ( aOR, 1.4; 95% CI, 1.1 - 1.7), number of prior hospital admissions ( aOR, 1.3; 95% CI, 1.1 - 1.6), and number of comorbid conditions ( aOR, 1.3; 95% CI, 1.1 - 1.5). Conclusions. The increase in the number of cases of C. difficile - associated disease was not attributable to a formulary change of fluoroquinolones; instead, the incidence was within expected seasonal variations for C. difficile associated disease. Recognition of community- acquired cases and the use of culture may help to identify additional cases of C. difficile - associated disease. Early diagnosis and treatment of C. difficile cases may shorten the duration of hospital stays and reduce the number of outbreaks and readmissions, mortality, and other consequences of C. difficile infection. C1 VA Puget Sound Hlth Care Syst, Dept Hlth Serv Res & Dev, Seattle, WA 98101 USA. VA Puget Sound Hlth Care Syst, Dept Infect Control, Seattle, WA 98101 USA. VA Puget Sound Hlth Care Syst, Lab Serv, Seattle, WA 98101 USA. VA Puget Sound Hlth Care Syst, Dermatol Sect, Primary & Specialty Serv, Seattle, WA 98101 USA. Univ Washington, Sch Pharm, Dept Med Chem, Seattle, WA 98195 USA. Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. Univ Washington, Dept Med, Div Dermatol, Seattle, WA 98195 USA. RP McFarland, LV (reprint author), VA Puget Sound Hlth Care Syst, Dept Hlth Serv Res & Dev, S152,1100 Olive Way 1400, Seattle, WA 98101 USA. EM Lynne.McFarland@va.gov NR 14 TC 69 Z9 73 U1 0 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 1 PY 2007 VL 45 IS 9 BP 1141 EP 1151 DI 10.1086/522187 PG 11 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 217BP UT WOS:000249923700004 PM 17918075 ER PT J AU Johansen, KL AF Johansen, Kirsten L. TI Value of quality improvement reporting SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Editorial Material C1 San Francisco VA Med Ctr, Nephrol Sect, San Francisco, CA 94121 USA. Univ Calif San Francisco, Div Nephrol, San Francisco, CA 94143 USA. RP Johansen, KL (reprint author), San Francisco VA Med Ctr, Nephrol Sect, 111J,4150 Clement St, San Francisco, CA 94121 USA. EM kirsten.johansen@ucsf.edu NR 9 TC 2 Z9 2 U1 1 U2 1 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD NOV PY 2007 VL 2 IS 6 BP 1104 EP 1105 DI 10.2215/CJN.03800907 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 225TC UT WOS:000250539400004 PM 17928462 ER PT J AU Hotchkiss, JR Holley, P Crooke, PS AF Hotchkiss, John R. Holley, Paul Crooke, Philip S. TI Analyzing pathogen transmission in the dialysis unit: Time for a (schedule) change? SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID VANCOMYCIN-RESISTANT ENTEROCOCCI; ACUTE RESPIRATORY SYNDROME; STAPHYLOCOCCUS-AUREUS; METHICILLIN-RESISTANT; PANDEMIC INFLUENZA; INANIMATE SURFACES; PREDICTION RULE; HUMAN HANDS; HEMODIALYSIS; SURVIVAL AB Background and objectives: Infectious diseases and antimicrobial-resistant microorganisms are a growing problem for the dialysis population. The frequency of patient visits and intimate, prolonged physical contact with the inanimate environment during dialysis treatments make these facilities potentially efficient venues for nosocomial pathogen transmission. Isolation measures and infection control practices can be inconvenient and consume limited resources. Quantitative tools for analyzing the effects of different containment strategies can help to identify optimal strategies for further study. However, spatial and temporal considerations germane to the dialysis unit greatly complicate analyses relying on conventional mathematical approaches. Design, setting, participants, & measurements: A stochastic, individual-based, Monte Carlo simulation tool that predicts the effects of various infection control strategies on pathogen dissemination through the dialysis unit in the face of diagnostic uncertainty was developed. The model was configured to emulate a medium-sized dialysis unit. The predicted consequences of various policies for scheduling patients who were suspected of being infectious were then explored, using literature-based estimates of pathogen transmissibility, prevalence, and diagnostic uncertainty. Results: Environmental decontamination was predicted to be of paramount importance in limiting pathogen dissemination. Temporal segregation (scheduling patients who were suspected of being infectious to dialysis shifts that are later in the day) was predicted to have the greatest effectiveness in reducing transmission, given adequate environmental decontamination between successive days. Conclusions: Decontamination of the patient's environment (chair) can markedly attenuate pathogen dissemination. Temporal segregation could be a simple, low-cost, system-level intervention with significant potential to reduce nosocomial transmission in the dialysis unit. C1 Univ Pittsburgh, Dept Crit Care Med, Pittsburgh, PA 15261 USA. Vet Affairs Pittsburgh Healthcare Syst, Renal Sect, Pittsburgh, PA USA. Holley Associates, Ashburn, VA USA. Vanderbilt Univ, Dept Math, Nashville, TN USA. RP Hotchkiss, JR (reprint author), Univ Pittsburgh, Dept Crit Care Med, 646 Scaife Hall,3550 Terrace St, Pittsburgh, PA 15261 USA. EM HotchkissJR@upmc.edu RI Crooke, Philip/B-5406-2008 OI Crooke, Philip/0000-0003-3872-3290 FU NIAID NIH HHS [1R21AI55818] NR 45 TC 4 Z9 4 U1 0 U2 0 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-9041 J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD NOV PY 2007 VL 2 IS 6 BP 1176 EP 1185 DI 10.2215/CJN.00130107 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 225TC UT WOS:000250539400016 PM 17962421 ER PT J AU Felsenfeld, AJ Rodriguez, M Aguilera-Tejero, E AF Felsenfeld, Arnold J. Rodriguez, Mariano Aguilera-Tejero, Escolastico TI Dynamics of parathyroid hormone secretion in health and secondary hyperparathyroidism SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Review ID CALCIUM-SENSING RECEPTOR; VITAMIN-D DEFICIENCY; SERUM IONIZED CALCIUM; ZEALAND WHITE-RABBIT; BASAL PLASMA CALCIUM; SET-POINT; HEMODIALYSIS-PATIENTS; RENAL-FAILURE; PTH SECRETION; IN-VITRO AB This review examines the dynamics of parathyroid hormone secretion in health and in various causes of secondary hyperparathyroidism. Although most studies of parathyroid hormone and calcium have focused on the modification of parathyroid hormone secretion by serum calcium, the relationship between parathyroid hormone and serum calcium is bifunctional because parathyroid hormone also modifies serum calcium. In normal animals and humans, factors such as phosphorus and vitamin D modify the basal parathyroid hormone level and the maximal parathyroid hormone response to hypocalcemia. Certain medications, such as lithium and estrogen, in normal individuals and sustained changes in the serum calcium concentration in hemodialysis patients change the set point of calcium, which reflects the serum calcium concentration at which parathyroid hormone secretion responds. Hypocalcemia increases the basal/maximal parathyroid hormone ratio, a measure of the relative degree of parathyroid hormone stimulation. The phenomenon of hysteresis, defined as a different parathyroid hormone value for the same serum calcium concentration during the induction of and recovery from hypo- and hypercalcemia, is discussed because it provides important insights into factors that affect parathyroid hormone secretion. In three causes of secondary hyperparathyroidism-chronic kidney disease, vitamin D deficiency, and aging-factors that affect the dynamics of parathyroid hormone secretion are evaluated in detail. During recovery from vitamin D deficiency, the maximal parathyroid hormone remains elevated while the basal parathyroid hormone value rapidly becomes normal because of a shift in the set point of calcium. Much remains to be learned about the dynamics of parathyroid hormone secretion in health and secondary hyperparathyroidism. C1 VA Greater Los Angeles Healthcare, Dept Med, Nephrol Sect 111L, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Los Angeles, CA USA. Hosp Univ Reina Sofia, Dept Nefrol, Cordoba, Spain. Hosp Univ Reina Sofia, Unidad Invest, Cordoba, Spain. Univ Cordoba, Dept Med & Cirugia Anim, Cordoba, Spain. RP Felsenfeld, AJ (reprint author), VA Greater Los Angeles Healthcare, Dept Med, Nephrol Sect 111L, 11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM Arnold.Felsenfeld@med.va.gov RI Rodriguez, teresa/H-5452-2011 NR 146 TC 36 Z9 37 U1 0 U2 7 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-905X J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD NOV PY 2007 VL 2 IS 6 BP 1283 EP 1305 DI 10.2215/CJN.01520407 PG 23 WC Urology & Nephrology SC Urology & Nephrology GA 225TC UT WOS:000250539400032 PM 17942777 ER PT J AU Rutkove, SB Zhang, H Schoenfeld, DA Raynor, EM Shefner, JM Cudkowicz, ME Chin, AB Aaron, R Shiffman, CA AF Rutkove, Seward B. Zhang, Hui Schoenfeld, David A. Raynor, Elizabeth M. Shefner, Jeremy M. Cudkowicz, Merit E. Chin, Anne B. Aaron, Ronald Shiffman, Carl A. TI Electrical impedance myography to assess outcome in amyotrophic lateral sclerosis clinical trials SO CLINICAL NEUROPHYSIOLOGY LA English DT Article DE amyotrophic lateral sclerosis; clinical trials methodology; electrical impedance myography; outcome measures ID NEUROMUSCULAR DISEASE; ALS; RESISTIVITY; PLACEBO; MUSCLE AB Objective: Standard outcome measures used for amyotrophic lateral sclerosis (ALS) clinical trials, including the ALS functional rating scale-revised (ALSFRS-R), maximal voluntary isometric contraction testing (MVICT), and manual muscle testing (MMT), are limited in their ability to detect subtle disease progression. Electrical impedance myography (EIM) is a new non-invasive technique that provides quantitative data on muscle health by measuring localized tissue impedance. This study investigates whether EIM could provide a new outcome measure for use in ALS clinical trials work. Methods: Fifteen ALS patients underwent repeated EIM measurements of one or more muscles over a period of up to 18 months and the primary outcome variable, theta(z-max), measured. The theta(z-max) megascore was then calculated using the same approach as has been applied in the past for MVICT. This and the MMT data were then used to assess each measure's statistical power to detect a given effect on disease progression in a hypothetical planned clinical therapeutic trial. Results: theta(z-max) showed a mean decline of about 21% for the test period, averaged across all patients and all tested muscles. The theta(z-max) megascore had a power of 73% to detect a 10% treatment effect in our planned hypothetical trial, as compared to a 28% power for MMT. These results also compared favorably to historical data for ALSFRS-R and MVICT arm megascore from the trial of celecoxib in ALS, where both measures had only a 23% power to detect the same 10% treatment effect. Conclusions: The theta(z-max), megascore may provide a powerful new outcome measure for ALS clinical trials. Significance: The application of EIM to future ALS trials may allow for smaller, faster studies with an improved ability to detect subtle progression of the disease and treatment effects. (c) 2007 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. C1 Harvard Univ, Beth Israel Deaconess Med Ctr, Dept Neurol, Sch Med, Boston, MA 02215 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurol Clin Trials Unit, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA 02114 USA. Northeastern Univ, Dept Phys, Boston, MA 02115 USA. SUNY Upstate Med Univ, Dept Neurol, Syracuse, NY 13210 USA. RP Rutkove, SB (reprint author), 330 Brookline Ave,TCC-810, Boston, MA 02446 USA. EM srutkove@bidmc.harvard.edu FU NCRR NIH HHS [M01 RR001032, RR01032]; NINDS NIH HHS [R01 NS042037-04, R01-NS42037-01A2, R01 NS042037-03, R01 NS042037] NR 19 TC 54 Z9 55 U1 0 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1388-2457 J9 CLIN NEUROPHYSIOL JI Clin. Neurophysiol. PD NOV PY 2007 VL 118 IS 11 BP 2413 EP 2418 DI 10.1016/j.clinph.2007.08.004 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 231KT UT WOS:000250946400011 PM 17897874 ER PT J AU Costello, D Davis, J Venna, N AF Costello, Daniel Davis, John Venna, Nagagopal TI HIV infection with immunodeficiency presenting with subacute cognitive decline: Recent illustrative cases SO CNS SPECTRUMS LA English DT Article ID PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; AIDS DEMENTIA COMPLEX; CEREBROSPINAL-FLUID; IMPAIRMENT; PREVALENCE; THERAPY AB We describe three recent patients in whom evaluation of subacute, progressive encephalopathy led to the initial diagnosis of human immunodeficiency virus infection. The clinical neurological picture of a predominance of abnormalities of mental function with few elementary neurological deficits, in conjunction with a paucity of systemic symptoms and lack of evidence for prior opportunistic infections preceding the encephalopathy are notable. The cognitive, behavioral, and neuropsychiatric disturbances are described in detail to illustrate the range of manifestations of disordered mental states associated with encephalopathy in individuals with HIV infection. The importance of a comprehensive and broad-minded work-up by brain magnetic resonance imaging, cerebrospinal fluid examination, and specific microbiological tests in delineating the potential multifactorial pathogenesis of the cerebral syndromes in relation to the HIV infection is emphasized.The gratifying long-term clinical improvements in parallel with resolution of neuroimaging and other laboratory abnormalities in response to antiretroviral drug treatment are reported. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Neurol, Cambridge, MA 02138 USA. RP Costello, D (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. EM dicostello@partners.org NR 16 TC 1 Z9 1 U1 0 U2 0 PU M B L COMMUNICATIONS, INC PI NEW YORK PA 333 HUDSON ST, 7TH FLOOR, NEW YORK, NY 10013 USA SN 1092-8529 J9 CNS SPECTRUMS JI CNS Spectr. PD NOV PY 2007 VL 12 IS 11 BP 842 EP 850 PG 9 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 232GA UT WOS:000251005200009 PM 17984857 ER PT J AU Wagner, AW Zatzick, DF Ghesquiere, A Jurkovich, GJ AF Wagner, Amy W. Zatzick, Douglas F. Ghesquiere, Angela Jurkovich, Gregory J. TI Behavioral activation as an early intervention for posttraumatic stress disorder and depression among physically injured trauma survivors SO COGNITIVE AND BEHAVIORAL PRACTICE LA English DT Article ID RANDOMIZED EFFECTIVENESS TRIAL; MUTUAL MAINTENANCE; SYMPTOMS; PAIN; PTSD; COMORBIDITY; ACCIDENT; PROGRESS; THERAPY; VICTIMS AB This paper describes an adaptation of behavioral activation (BA)for the early intervention of posttraumatic stress disorder (PTSD) and depression among physically injured survivors of traumatic injury, and presents pilot data on a small randomized effectiveness trial (N = 8). The application of BA to PTSD is based on the theory that increases in guided activity may break patterns of avoidance that can maintain PTSD. Compared to treatment as usual (TA U), those who received BA showed improvement in PTSD symptom severity from. Pre- to posttreatment, and there was a trend for the BA group to score better than the TAU group on physical functioning. Contrary to expectation, this brief adaptation did not have an impact on depression. Implications of these results for the effective early intervention after trauma are discussed. C1 Univ Washington, Seattle, WA 98195 USA. RP Wagner, AW (reprint author), Portland VA Med Ctr, POB 1035,V3-SATP, Portland, OR 97207 USA. EM amy.wagner@va.gov NR 47 TC 51 Z9 52 U1 3 U2 10 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 2007 VL 14 IS 4 BP 341 EP 349 DI 10.1016/j.cbpra.2006.05.002 PG 9 WC Psychology, Clinical SC Psychology GA 322WZ UT WOS:000257407300001 ER PT J AU Estepar, RSJ Stylopoulos, N Ellis, R Samset, E Westin, CF Thompson, C Vosburgh, K AF Estepar, Raul San Jose Stylopoulos, Nicholas Ellis, Randy Samset, Eigil Westin, Carl-Fredrik Thompson, Christopher Vosburgh, Kirby TI Towards scarless surgery: An endoscopic ultrasound navigation system for transgastric access procedures SO COMPUTER AIDED SURGERY LA English DT Article; Proceedings Paper CT 9th International Conference on Medical Image Computing and Computer-Assisted Intervention (MICCAI 2006) CY OCT 01-06, 2006 CL Copenhagen, DENMARK SP AstraZeneca, Ctr Clin & Basic Res, Claron, Elsevier, General Elect, Medtronic, No Digital Inc, Siemens Corp Res, Springer, Visiopharm DE ultrasound; navigation; endoscopy; natural orifice; transgastric approach ID PORCINE MODEL; LAPAROSCOPIC ULTRASOUND; CALIBRATION; SURVIVAL AB Objective: Scarless surgery is an innovative and promising technique that may herald a new era in surgical procedures. We have created a navigation system, named IRGUS, for endoscopic and transgastric access interventions and have validated it in in vivo pilot studies. Our hypothesis is that endoscopic ultrasound procedures will be performed more easily and efficiently if the operator is provided with approximately registered 3D and 2D processed CT images in real time that correspond to the probe position and ultrasound image. Materials and Methods: The system provides augmented visual feedback and additional contextual information to assist the operator. It establishes correspondence between the real-time endoscopic ultrasound image and a preoperative CT volume registered using electromagnetic tracking of the endoscopic ultrasound probe position. Based on this positional information, the CT volume is reformatted in approximately the same coordinate frame as the ultrasound image and displayed to the operator. Results: The system reduces the mental burden of probe navigation and enhances the operator's ability to interpret the ultrasound image. Using an initial rigid body registration, we measured the mis-registration error between the ultrasound image and the reformatted CT plane to be less than 5 mm, which is sufficient to enable the performance of novice users of endoscopic systems to approach that of expert users. Conclusions: Our analysis shows that real-time display of data using rigid registration is sufficiently accurate to assist surgeons in performing endoscopic abdominal procedures. By using preoperative data to provide context and support for image interpretation and real-time imaging for targeting, it appears probable that both preoperative and intraoperative data may be used to improve operator performance. C1 [Estepar, Raul San Jose; Ellis, Randy; Samset, Eigil; Westin, Carl-Fredrik; Thompson, Christopher; Vosburgh, Kirby] Brigham & Womens Hosp, Boston, MA 02115 USA. [Stylopoulos, Nicholas; Vosburgh, Kirby] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Vosburgh, Kirby] CIMIT, Boston, MA 02114 USA. RP Estepar, RSJ (reprint author), 1249 Boylston St, Boston, MA 02215 USA. EM rjosest@bwh.harvard.edu FU NCRR NIH HHS [P41-RR13218] NR 29 TC 18 Z9 19 U1 1 U2 3 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1092-9088 J9 COMPUT AIDED SURG JI Comput. Aided Surg. PD NOV PY 2007 VL 12 IS 6 BP 311 EP 324 DI 10.1080/10929080701746892 PG 14 GA 305GE UT WOS:000256165000002 PM 18066947 ER PT J AU Bajwa, EK Boyce, PD Januzzi, JL Gong, MN Thompson, BT Christiani, DC AF Bajwa, Ednan K. Boyce, Paul D. Januzzi, James L. Gong, Michelle N. Thompson, B. Taylor Christiani, David C. TI Biomarker evidence of myocardial cell injury is associated with mortality in acute respiratory distress syndrome SO CRITICAL CARE MEDICINE LA English DT Article DE acute respiratory distress syndrome; prognosis; biological markers; troponin T; troponin I; creatine phosphokinase isoenzyme; myocardial band enzymes ID ACUTE LUNG INJURY; CRITICALLY-ILL PATIENTS; SEPTIC SHOCK; PULMONARY-ARTERY; RISK-FACTOR; DYSFUNCTION; TROPONIN; INFARCTION; HEART; RATS AB Objective. Although a number of studies have reported elevated levels of markers of myocardial necrosis among critically ill patients, the association between these markers and outcome remains poorly studied in patients with lung injury. We investigated the association of elevated troponin and creatine phosphokinase isoenzyme levels with mortality and organ failure in subjects with acute respiratory distress syndrome. Design: Retrospective study. Setting: Tertiary academic medical center. Patients: A total of 305 subjects with acute respiratory distress syndrome enrolled in a prospective intensive care unit cohort. Intervention: None. Measurements and Main Results. Cardiac biomarker data were available on 248 of 305 patients with acute respiratory distress syndrome (81%), of which 89 patients had at least one elevated cardiac marker level (35%). The presence of an elevated cardiac marker was associated with significantly higher mortality (p =.01) and was an independent predictor of mortality (p =.02) among patients with lower severity of illness (Acute Physiology and Chronic Health Evaluation III, <79). Patients with at least one elevated cardiac marker also had significantly more organ system derangement, including noncardiovascular organ system failures (p =.02). Conclusions. Patients with acute respiratory distress syndrome have a high prevalence of elevated cardiac markers. The presence of elevated cardiac markers is independently associated with increased 60-day mortality and increased organ failure. This association is most pronounced among patients with lower severity of illness. These results indicate that occult myocardial injury may be an important factor in acute respiratory distress syndrome morbidity and mortality. Further study of the relevant causal relationships and mechanisms is warranted. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiol Unit, Boston, MA 02115 USA. Mt Sinai Sch Med, Div Pulm & Crit Care, New York, NY USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. RP Bajwa, EK (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02115 USA. EM dchristi@hsph.harvard.edu FU NHLBI NIH HHS [HL67197, HL60710, HL07874] NR 39 TC 28 Z9 28 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD NOV PY 2007 VL 35 IS 11 BP 2484 EP 2490 DI 10.1097/01.CCM.0000281852.36573.22 PG 7 WC Critical Care Medicine SC General & Internal Medicine GA 224CN UT WOS:000250423500002 PM 18084839 ER PT J AU Bigatello, LM Stelfox, HT Berra, L Schmidt, U Gettings, EM AF Bigatello, Luca M. Stelfox, Henry Thomas Berra, Lorenzo Schmidt, Ulrich Gettings, Elise M. TI Outcome of patients undergoing prolonged mechanical ventilation after critical illness SO CRITICAL CARE MEDICINE LA English DT Article DE prolonged mechanical ventilation; prolonged critical illness; acute respiratory failure; weaning from mechanical ventilation ID RESPIRATORY-DISTRESS-SYNDROME; REGIONAL WEANING CENTER; TERM-CARE HOSPITALS; INTENSIVE-CARE; CATASTROPHIC ILLNESS; CONSENSUS CONFERENCE; DECISION-MAKING; SYNDROME ARDS; SURVIVORS; FACILITIES AB Objective: To examine the longitudinal outcome of a cohort of mechanically ventilated patients admitted to an acute care respiratory unit after critical illness. Design, Setting, and Patients., Prospective, observational study of 210 consecutive patients admitted to a respiratory unit of an acute, tertiary care university hospital, who had an acute critical illness with respiratory failure. The study was powered to develop multivariate regression models to investigate the relationship between patient characteristics and a) liberation from mechanical ventilation and b) survival. Interventions: None. Measurements and Main Results: The median time to liberation from mechanical ventilation after respiratory unit admission was 14 days (interquartile range, 6-51). A total of 146 patients (69%) were off mechanical ventilation at 6 months, and 123 patients (61%) were alive at 1 yr. Patients who did not come off mechanical ventilation in the respiratory unit were seven times more likely to die within a year than those who did (odds ratio, 6.55; 95% confidence intervals, 4.04-10.63; p <.001). At least 75% of deaths occurred by consensual withdrawal of life support. Patient activity of daily living scores (0-100 scale) increased progressively from hospital discharge (24 :L 6) through 3 (54 +/- 21) and 6 months (64 22) (p <.001). The median cost of hospitalization for all study patients was $149,624 (interquartile range, $102,540-225,W). Conclusions. The majority of patients requiring prolonged mechanical ventilation in a respiratory unit after acute critical illness are liberated from mechanical ventilation, survive, and have a steady improvement in the activity of daily living during the first 6 months after discharge. However, a substantial fraction of these patients does not wean from mechanical ventilation and dies from consensual withdrawal of life support after a prolonged and costly hospital stay. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Cambridge, MA 02138 USA. Univ Calgary, Dept Crit Care Med, Calgary, AB, Canada. RP Bigatello, LM (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Cambridge, MA 02138 USA. EM Lbigatello@partners.org NR 25 TC 43 Z9 43 U1 3 U2 4 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 2007 VL 35 IS 11 BP 2491 EP 2497 DI 10.1097/01.CCM.0000287589.16724.B2 PG 7 WC Critical Care Medicine SC General & Internal Medicine GA 224CN UT WOS:000250423500003 PM 17901840 ER PT J AU Wirth, LJ Posner, MR AF Wirth, Lori J. Posner, Marshall R. TI Recent advances in combined modality therapy for locally advanced head and neck cancer SO CURRENT CANCER DRUG TARGETS LA English DT Review DE squamous cell carcinoma of the head and neck; chemoradiotherapy; sequential therapy ID ADVANCED LARYNGEAL-CANCER; SQUAMOUS-CELL CARCINOMA; PROSPECTIVE RANDOMIZED-TRIAL; STAGE OROPHARYNX CARCINOMA; PHASE-III TRIAL; RADIATION-THERAPY; CONCURRENT CHEMOTHERAPY; CONCOMITANT RADIOCHEMOTHERAPY; ACCELERATED RADIOTHERAPY; NEOADJUVANT CHEMOTHERAPY AB Half of all patients with squamous cell carcinoma of the head and neck (SCCHN) present with locally advanced disease. Despite the development of new treatment strategies, mortality rates have only improved over the last decade by 2.6% per year, and prognosis remains poor. Combined modality therapy offers the potential for organ preservation, particularly for tumors arising in the larynx, hypopharynx and oropharynx. Organ preservation with concurrent chemoradiotherapy (CRT) was first established in laryngeal carcinoma. Recent results of the laryngeal study, RTOG 9111, indicate that even though larynx preservation is improved with CRT compared to induction chemotherapy followed by radiotherapy alone, laryngectomy-free survival is the same. Future attentions should be focused not only on improving treatment efficacy, but also on efforts to minimize the long term toxicities of therapy for SCCHN, particularly because long term toxicities not only diminish quality of life, but seem to impact on survival. In the future, targeted therapies may be incorporated into combined modality therapy for SCCHN, offering the chance to enhance the anticancer effects of treatment without increasing toxicity. Improvements in radiotherapy techniques may also move the field forward. Finally, there is renewed interest in the role of induction chemotherapy as part of a sequential treatment approach for advanced SCCHN If the current generation of studies evaluating sequential therapy is favorable, future studies incorporating targeted therapies into this platform will offer further potential for advancing the treatment of SCCHN. C1 [Wirth, Lori J.; Posner, Marshall R.] Harvard Med Sch, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA USA. RP Wirth, LJ (reprint author), Dana Farber Canc Inst, 44 Binny St, Boston, MA 02115 USA. EM Lori_Wirth@dfci.harvard.edu NR 49 TC 9 Z9 9 U1 0 U2 3 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1568-0096 J9 CURR CANCER DRUG TAR JI Curr. Cancer Drug Targets PD NOV PY 2007 VL 7 IS 7 BP 674 EP 680 DI 10.2174/156800907782418329 PG 7 WC Oncology SC Oncology GA 242OK UT WOS:000251734900009 PM 18045072 ER PT J AU Kramer, VG Siddappa, NB Ruprecht, RM AF Kramer, Victor G. Siddappa, Nagadenahalli B. Ruprecht, Ruth M. TI Passive immunization as tool to identify protective HIV-1 Env epitopes SO CURRENT HIV RESEARCH LA English DT Review DE passive immunization; epitopes; neutralizing antibodies; SHIV ID HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN MONOCLONAL-ANTIBODY; T-CELL DEPLETION; PIG-TAILED MACAQUES; HUMAN NEUTRALIZING ANTIBODIES; PROXIMAL EXTERNAL REGION; TYPE-1 SUBTYPE-C; CD4 BINDING-SITE; RHESUS MACAQUES; IN-VIVO AB The HIV-1/AIDS epidemic continues to escalate, and a protective vaccine remains elusive. The first vaccine candidate, gp120, did not induce broadly neutralizing antibodies (nAbs) against primary HIV-1 isolates and was ineffective in phase III clinical trials. Attention then focused on generating cytotoxic lymphocyte (CTL)-based vaccines. Interest in anti-HIV-1 nAbs was renewed when passive immunization with human neutralizing monoclonal antibodies (nmAbs) completely protected macaques after intravenous and mucosal challenges with simian-human immunodeficiency viruses (SHIVs) encoding HIV-1 env. These nmAbs targeted conserved, functionally important epitopes on gp120 and gp41. Protection in primate/SHIV models was observed when nmAbs were used singly (nmAbs 2G 12, b 12) and in various combination regimens (nmAbs b12, F105, 2G12, 2F5, 4E10). Passive immunization. a well-established tool to determine the correlates of protective immunity, thus identified protective epitopes. The three-dimensional structures of some of the latter were recently elucidated, generating important information to design nAb-response-base immunogens. However, several of the protective nmAbs were found to exhibit autoreactivity, raising the possibility that B-cell responses against the cognate epitopes may be difficult to induce by active immunization. It will be important to explore whether broad neutralization can be dissociated from autoreactivity. Future experiments will reveal whether other conserved HIV-1 Env epitopes exist, antibodies against which will be broadly neutralizing in vitro, protective as passive immunization in SHIV-challenged macaques, but lacking autoreactivity. Since all protective epitopes identified to date are located on HIV-1 clade B Env, future studies should include analysis of nmAbs against non-clade B strains. C1 [Siddappa, Nagadenahalli B.; Ruprecht, Ruth M.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Kramer, Victor G.; Siddappa, Nagadenahalli B.; Ruprecht, Ruth M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Ruprecht, RM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. EM rtitil_ruprecht@dfci.harvard.edu OI Byrareddy, Siddappa /0000-0002-7423-1763 FU NIAID NIH HHS [R37 AI43839, P01 AI48240]; NIDCR NIH HHS [R01 DE016013] NR 146 TC 25 Z9 26 U1 1 U2 1 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1570-162X J9 CURR HIV RES JI Curr. HIV Res. PD NOV PY 2007 VL 5 IS 6 BP 642 EP 655 DI 10.2174/157016207782418506 PG 14 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 269EZ UT WOS:000253633600013 PM 18045119 ER PT J AU Reiser, J Mundel, P AF Reiser, Jocben Mundel, Peter TI Dual effects of RAS blockade on blood pressure and podocyte function SO CURRENT HYPERTENSION REPORTS LA English DT Article ID CONVERTING ENZYME-INHIBITION; RENIN-ANGIOTENSIN SYSTEM; PASSIVE HEYMANN NEPHRITIS; TYPE-2 DIABETES-MELLITUS; IN-VITRO; SEGMENTAL GLOMERULOSCLEROSIS; GLOMERULAR PODOCYTES; KIDNEY-DISEASE; SLIT DIAPHRAGM; RATS AB There is no question about the contributory risk of hypertension in morbidity and mortality from cardiovascular (CV) disease and chronic kidney disease (CKD). Another independent risk factor for CV disease and CKD is proteinuria, which is most commonly caused by dysfunction of the kidney glomerular filter, in particular of the podocyte. Podocytes are highly differentiated pericyte-like cells that are essential to normal kidney function. Moreover, loss of podocytes is a hallmark of diabetic and nondiabetic progressive CKD. Recent data point to an important role for the renin-angiotensin system (RAS) and calcium signaling in the structural and functional integrity of podocytes. Given this scenario, it is desirable to treat hypertension with agents targeting the RAS, such as angiotensin-converting enzyme (ACE) inhibitors and angiotensin II (Ang II) type 1-receptor blockers (ARB). These agents have proven effects on lowering blood pressure (BP) and can reduce podocyte injury. Here we review the dual effects of RAS blockade on BP and on podocyte function and emphasize BP-dependent and BP-independent effects of this regimen. C1 [Reiser, Jocben] Massachusetts Gen Hosp, Div Nephrol, Program Glomerular Dis, Boston, MA 02129 USA. RP Reiser, J (reprint author), Massachusetts Gen Hosp, Div Nephrol, Program Glomerular Dis, CNY-149,13th St,Suite 8214, Boston, MA 02129 USA. EM jreiser@partners.org FU NIDA NIH HHS [DA18886]; NIDDK NIH HHS [DK064236, DK073495, DK062472, DK57683] NR 66 TC 21 Z9 25 U1 0 U2 0 PU CURRENT SCIENCE INC PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1522-6417 J9 CURR HYPERTENS REP JI Curr. Hypertens. Rep. PD NOV PY 2007 VL 9 IS 5 BP 403 EP 408 DI 10.1007/s11906-007-0074-7 PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 269VL UT WOS:000253678300013 PM 18177588 ER PT J AU Fischman, AJ Badgaiyan, RD AF Fischman, Alan J. Badgaiyan, Rajendra D. TI Functional imaging of neurotransmission SO CURRENT MEDICAL IMAGING REVIEWS LA English DT Review DE dopamine; raclopride; fallypride; memory; motor planning; molecular imaging ID POSITRON-EMISSION-TOMOGRAPHY; STRIATAL DOPAMINE RELEASE; D2 RECEPTOR DENSITY; AMPHETAMINE-INDUCED DISPLACEMENT; HUMAN-BRAIN; IN-VIVO; NONHUMAN-PRIMATES; F-18 FALLYPRIDE; BASAL GANGLIA; EXTRASTRIATAL REGIONS AB Functional neurotransmitter imaging (fNTI) is an evolving technique that uses molecular imaging to detect neurotransmitters released during a task performance. This technique provides a tool to study neurochemistry of human cognition and involves dynamic measurement of the concentration of a specific radioligand during the task performance. Since ligands are competitively displaced by endogenously released neurotransmitters, a reduction in ligand concentration during task performance indicates task-induced release of endogenous neurotransmitter. Most of the INTI experiments have used a specific dopamine receptor ligand C-11-raclopride, which is suitable only for detection of dopamine released in the striatum. Ligands such as F-18-fallypride and C-11-FLB456 are potential candidates for detection of extrastriatal dopamine release. Using this technique, we have studied striatal and extrastriatal dopamine neurotransmission during performance of a variety of cognitive and behavioral tasks. These tasks include, motor planning, conscious and nonconscious motor memory, cured-recall, response inhibition and emotional memory. Since, fNTI is an emerging technique, it has so far been used to study only dopaminergic neurotransmission. Its utility in the study of human brain and cognition depends critically on the development of appropriate ligands for other neurotransmitters. C1 [Fischman, Alan J.; Badgaiyan, Rajendra D.] Harvard Univ, Massachusetts Gen Hosp, Shriners Hosp Children, Sch Med Div Nucl Med, Boston, MA 02114 USA. RP Fischman, AJ (reprint author), Massachusetts Gen Hosp, Div Nucl Med, 55 Fruit Str, Boston, MA 02114 USA. EM fischman@pet.mgh.harvard.edu NR 58 TC 0 Z9 0 U1 4 U2 8 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1573-4056 J9 CURR MED IMAGING REV JI Curr. Med. Imaging Rev. PD NOV PY 2007 VL 3 IS 4 BP 220 EP 224 DI 10.2174/157340507782446287 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 243JF UT WOS:000251791900002 ER PT J AU Xiang, Z Thomas, S Pasinetti, G AF Xiang, Zhongmin Thomas, Sunil Pasinetti, Giulio TI Increased neuronal injury in transgenic mice with neuronal overexpression of human cyclooxygenase-2 is reversed by hypothermia and rofecoxib treatment SO CURRENT NEUROVASCULAR RESEARCH LA English DT Article DE COX-2; ischemia; hypothermia; rofecoxib; stroke ID FOCAL CEREBRAL-ISCHEMIA; NITRIC-OXIDE SYNTHASE; CELL-CYCLE ACTIVITY; MILD HYPOTHERMIA; MESSENGER-RNA; INHIBITOR ROFECOXIB; GLOBAL-ISCHEMIA; BRAIN-INJURY; INFLAMMATORY RESPONSE; ALZHEIMERS-DISEASE AB Cyclooxygenase-2 (COX-2) is up-regulated during ischemia. However, the role of COX-2 in neuronal injury is still unclear. in this study we tested whether neuronal overexpression of human COX-2 in a transgenic mouse model potentiates neuronal injury after global ischemic insult. Further, we tested whether the neuronal injury could be ameliorated by intra-ischemic mild hypothermia (33-34 degrees C) alone or in combination with diet treatment of rofecoxib, a COX-2 specific inhibitor. Global ischemia with intra-ischemic normothermia (36-37 degrees C) resulted in significantly higher neuronal damage in the CA1 region of hippocampus of transgenic mice than in wild type controls, confirming a deleterious role of COX-2 in ischemic neuronal damage. Hypothermia significantly reduced neuronal damage in both transgenic mice and wild type controls to the same extent, suggesting that the aggravating effect of COX-2 could be largely eliminated by hypothermia. When hypothermia was combined with rofecoxib treatment, neuronal damage was further reduced in response to global ischemia. The results suggest that COX-2 inhibition by prophylactic treatment with rofecoxib coupled with hypothermia at the time of acute stroke insult could be an effective therapeutic approach in early stages of stroke treatment in high risk patients. C1 [Xiang, Zhongmin; Thomas, Sunil; Pasinetti, Giulio] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. [Pasinetti, Giulio] Mt Sinai Sch Med, Dept Neurosci, New York, NY USA. [Thomas, Sunil; Pasinetti, Giulio] James J Peters Vet Aff Med Ctr, Geriat Res & Clin Ctr, Bronx, NY 10468 USA. RP Pasinetti, G (reprint author), Mt Sinai Sch Med, Dept Psychiat, E Bldg Rm 10-70,One Gustav L,Levy Pl, New York, NY 10029 USA. EM giulio.pasinetti@mssm.edu FU NIA NIH HHS [AG13799] NR 46 TC 18 Z9 18 U1 0 U2 1 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1567-2026 J9 CURR NEUROVASC RES JI Curr. Neurovasc. Res. PD NOV PY 2007 VL 4 IS 4 BP 274 EP 279 DI 10.2174/156720207782446342 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 242OB UT WOS:000251733900007 PM 18045153 ER PT J AU Ham, M Kaunitz, JD AF Ham, Maggie Kaunitz, Jonathan D. TI Gastroduodenal defense SO CURRENT OPINION IN GASTROENTEROLOGY LA English DT Article DE cyclooxygenase; defense; duodenum; esophagus; glucocorticoid; injury ID GASTRIC-MUCOSAL INTEGRITY; INDUCED INTESTINAL DAMAGE; GROWTH-FACTOR-ALPHA; HYDROGEN-SULFIDE; GASTROINTESTINAL INFLAMMATION; SIGNALING PATHWAYS; TREFOIL PEPTIDES; EPITHELIAL-CELLS; COX-2 INHIBITOR; TFF2 EXPRESSION AB Purpose of review The gastroduodenum resists mucosal injury despite continuous exposure to concentrated gastric acid. The mucosal barrier consists of a preepithelial mucus HCO3 layer, intercellular tight junctions connecting the epithelial cells, and submucosal acid sensors, prostaglandins, cytokines, enteric nerves and blood flow. In the past year, study of these defensive mechanisms has revealed new insight into the observed sex differences in ulcer prevalence, the protective role of transforming growth factor, the role of serotonin in regulating HCO3- secretion, the role of mechanisms in ulcer healing, the interaction of trefoil factors with the mucus gel, the interaction of glucocorticoids with cyclooxygenase and the characterization of novel, mucosal sparing antiinflammatory agents. Recent findings Transforming growth factor, melatonin, serotonin, trefoil factors and H2S all enhance mucosal barrier function or accelerate ulcer healing. Newer coxibs may have safety and advantages over existing compounds. Existing nonsteroidal antiinflammatory drugs may be safer than originally thought. Summary The continued elucidation of basic defense mechanisms has led to the development of several new compounds designed to enhance barrier function and repair mechanisms. C1 W Los Angeles Vet Affairs Med Ctr, Los Angeles, CA 90073 USA. WLAVA Med Ctr, Greater Los Angeles Vet Affairs Healthcare Syst, Los Angeles, CA USA. Div Digest Dis, Los Angeles, CA USA. Digest Dis Res Ctr, CURE, Los Angeles, CA USA. Dept Med, Los Angeles, CA USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. Brentwood Biomed Res Inst, Los Angeles, CA USA. RP Kaunitz, JD (reprint author), W Los Angeles Vet Affairs Med Ctr, MD Bldg 114,Suite 217, Los Angeles, CA 90073 USA. EM jake@ucla.edu FU PHS HHS [R01 54221] NR 70 TC 29 Z9 29 U1 0 U2 5 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 2007 VL 23 IS 6 BP 607 EP 616 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 223IR UT WOS:000250364000004 PM 17906436 ER PT J AU Hayden, PJ Mitsiades, CS Anderson, KC Richardson, PG AF Hayden, Patrick J. Mitsiades, Constantine S. Anderson, Kenneth C. Richardson, Paul G. TI Novel therapies in myeloma SO CURRENT OPINION IN HEMATOLOGY LA English DT Article DE bortezomib; immunomodulatory; myeloma; targeted therapy ID REFRACTORY MULTIPLE-MYELOMA; PEGYLATED LIPOSOMAL DOXORUBICIN; STEM-CELL TRANSPLANTATION; THALIDOMIDE PLUS DEXAMETHASONE; HIGH-DOSE DEXAMETHASONE; NEWLY-DIAGNOSED MYELOMA; TUMOR-MICROENVIRONMENTAL INTERACTIONS; COMBINATION THERAPY; UNTREATED PATIENTS; ELDERLY-PATIENTS AB Purpose of review Several novel therapies have been licensed for the treatment of myeloma in recent years. We summarize some of the trials leading to their approval and the current evidence for their clinical use. A number of promising agents undergoing phase I/II trial evaluation are also discussed. Recent findings The immunomodulatory drugs, thalidomide and lenalidomide, and the proteasome inhibitor, bortezomib, have been shown to be effective agents, both alone and as part of combination regimens, for the treatment of myeloma. Studies are now focusing on the optimal sequencing of these drugs throughout the disease course, with a view to maximizing antitumor efficacy and minimizing overlapping toxicities. New protocols are increasingly based on preclinical evidence of synergy. The incorporation of these agents into transplant-based treatment protocols has improved outcomes. Other examples of novel agents undergoing assessment at present include arsenic trioxide, hsp90 inhibitors and histone deacetylase inhibitors. Future developments are likely to include individualized treatment plans based on patient-specific parameters including cytogenetic analysis and gene expression profiling. Summary Thalidomide, lenalidomide and bortezomib can now be considered as standard options both as first-line agents and beyond for the treatment of myeloma, with respective combinations also emerging as valid choices for all stages of the disease. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Richardson, PG (reprint author), Dana Farber Canc Inst, 44 Binney St,Dana 1 B02, Boston, MA 02115 USA. EM paul_richardson@dfci.harvard.edu NR 72 TC 15 Z9 17 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1065-6251 J9 CURR OPIN HEMATOL JI Curr. Opin. Hematol. PD NOV PY 2007 VL 14 IS 6 BP 609 EP 615 DI 10.1097/MOH.0b013e3282f0e948 PG 7 WC Hematology SC Hematology GA 220OC UT WOS:000250165000001 PM 17898564 ER PT J AU Boker, A Kimball, AB Rolz-Cruz, G AF Boker, Andreas Kimball, Alexa B. Rolz-Cruz, Gabriela TI Biologicals in the treatment of psoriasis SO CURRENT OPINION IN INVESTIGATIONAL DRUGS LA English DT Article DE biological therapy; IL-12; IL-23; inflammation; mAb; psoriasis; psoriasis area and severity index; TNF ID CHRONIC PLAQUE PSORIASIS; PLACEBO-CONTROLLED TRIAL; RANDOMIZED CONTROLLED-TRIAL; CONTINUOUS EFALIZUMAB THERAPY; DOUBLE-BLIND; PHASE-III; RHEUMATOID-ARTHRITIS; INFLIXIMAB INDUCTION; CLINICAL-EXPERIENCE; ETANERCEPT AB Psoriasis is a chronic inflammatory skin disorder that can cause substantial disability. The recognition of psoriasis as an immunologically mediated disease led to the development of agents that specifically target key steps in the pathological process. This review focuses on these biological agents, and presents results from phase II and III clinical trials together with the safety profile and approved indications for alefacept, efalizumab, etanercept, infliximab and adalimumab. Preliminary safety and efficacy data for the newer therapeutic agents, such as CNTO-1275 and ABT-874, are also described. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Massachusetts Gen Hosp,Dept Dermatol, Boston, MA 02114 USA. RP Kimball, AB (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Massachusetts Gen Hosp,Dept Dermatol, 50 Staniford St 240, Boston, MA 02114 USA. EM harvardskinstudies@partners.org NR 49 TC 10 Z9 10 U1 0 U2 0 PU THOMSON SCIENTIFIC PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND STREET, LONDON, W1T 4JE, ENGLAND SN 1472-4472 J9 CURR OPIN INVEST DR JI Curr. Opin. Investig. Drugs PD NOV PY 2007 VL 8 IS 11 BP 939 EP 946 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 227FU UT WOS:000250643400008 PM 17979028 ER PT J AU Pikman, Y Levine, RL AF Pikman, Yana Levine, Ross L. TI Advances in the molecular characterization of Philadelphia-negative chronic myeloproliferative disorders SO CURRENT OPINION IN ONCOLOGY LA English DT Review DE essential thrombocythemia; JAK2 tyrosine kinase; myelofibrosis; myeloproliferative disorders; polycythemia vera; thrombopoietin receptor ID JAK2 V617F MUTATION; CHRONIC MYELOMONOCYTIC LEUKEMIA; CHRONIC MYELOCYTIC-LEUKEMIA; CHRONIC MYELOID-LEUKEMIA; KINASE INHIBITOR PKC412; ABL TYROSINE KINASE; POLYCYTHEMIA-VERA; ACTIVATING MUTATION; ESSENTIAL THROMBOCYTHEMIA; STEM-CELL AB Purpose of review The identification and characterization of somatic disease alleles have greatly improved our understanding of the molecular pathogenesis of myeloproliferative disorders. This review focuses on recent studies investigating the role of activated tyrosine kinase signaling in the Philadelphia chromosome negative myeloproliferative disorders. Recent findings Previously identified tyrosine kinase mutations in chronic myeloid leukemia and other myeloproliferative disorders suggested the possibility that polycythemia vera, essential thrombocythemia and primary myelofibrosis are also caused by activated tyrosine kinases. Recent studies identified an activating mutation in the JAK2 tyrosine kinase (JAK2V617F) in most patients with polycythemia vera and in approximately half of those with essential thrombocythemia and primary myelofibrosis. More recently, activating mutations in the thrombopoietin receptor and in JAK2 exon 12 have been identified in JAK2 V61 7F negative myeloproliferative disorders. Summary The discovery of activated tyrosine kinases in the majority of patients with polycythemia vera, essential thrombocythemia and primary myelofibrosis has diagnostic and pathogenetic implications. Subsequent studies are needed to elucidate the cause of myeloproliferative disorders without known disease alleles and to determine if inhibition of JAK2 signaling has therapeutic efficacy in the treatment of polycythemia vera, essential thrombocythemia and primary myelofibrosis. C1 Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10021 USA. Brigham & Womens Hosp, Dept Med, Div Hematol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Levine, RL (reprint author), Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, 1275 York Ave,Box 20, New York, NY 10021 USA. EM LevineR@mskcc.org OI Pikman, Yana/0000-0002-5336-0216 FU NHLBI NIH HHS [K08HL082677-01] NR 63 TC 7 Z9 7 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 1040-8746 EI 1531-703X J9 CURR OPIN ONCOL JI Curr. Opin. Oncol. PD NOV PY 2007 VL 19 IS 6 BP 628 EP 634 PG 7 WC Oncology SC Oncology GA 223IJ UT WOS:000250363200015 PM 17906464 ER PT J AU Andreoli, CM Miller, JW AF Andreoli, Christopher M. Miller, Joan W. TI Anti-vascular endothelial growth factor therapy for ocular neovascular disease SO CURRENT OPINION IN OPHTHALMOLOGY LA English DT Article DE age-related macular degeneration; diabetic retinopathy; neovascular glaucoma; neovascularization; retinopathy of prematurity; vascular endothelial growth factor ID PROLIFERATIVE DIABETIC-RETINOPATHY; RANDOMIZED CLINICAL-TRIAL; SUBFOVEAL CHOROIDAL NEOVASCULARIZATION; MACULAR DEGENERATION; BEVACIZUMAB AVASTIN; INTRAVITREAL BEVACIZUMAB; RETINAL NEOVASCULARIZATION; PHOTODYNAMIC THERAPY; VISUAL-LOSS; RUBOXISTAURIN AB Purpose of review Recent research has shown that vascular endothelial growth factor (VEGF) is responsible for many ocular pathologies involving neovascularization. Over the past several years several new agents targeting VEGF have become commercially available for intraocular use. These agents have revolutionized the care of neovascular age related macular degeneration and have great potential for other blinding conditions such as diabetic retinopathy, retinopathy of prematurity, and neovascular glaucoma. Recent findings The VEGF Inhibition Study in Ocular Neovascularization (VISION) trial first showed that an anti-VEGF agent (pegaptanib) was able to prevent vision loss in neovascular age related macular degeneration. The Minimally Classic/ Occult Trial of Anti-VEGF Antibody Ranibizumab in the Treatment of Neovascular AMD (MARINA) and Anti-VEGF Antibody for the Treatment of Predominantly Classic Choroidal Neovascularization in AMD (ANCHOR) trials showed that ranibizumab prevented moderate vision loss in neovascular age related macular degeneration and for the first time that a substantial proportion of patients regained vision. Smaller case series have shown that bevacizumab can regress retinal, iris and disc neovascularization. Ongoing trials are investigating the utility of anti-VEGF therapy in retinopathy of prematurity, diabetic retinopathy, and neovascular glaucoma. Summary Newer anti-VEGF therapies have shown unprecedented efficacy in treating age related macular degeneration with many patients experiencing improvement in vision. Ongoing trials will help guide their use in age related macular degeneration and expand their indications to many other blinding diseases. 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 50 TC 141 Z9 146 U1 1 U2 15 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8738 J9 CURR OPIN OPHTHALMOL JI Curr. Opin. Ophthalmol. PD NOV PY 2007 VL 18 IS 6 BP 502 EP 508 DI 10.1097/ICU.0b013e3282f0ca54 PG 7 WC Ophthalmology SC Ophthalmology GA 228AJ UT WOS:000250698900010 PM 18163003 ER PT J AU Schafer, I Najavits, LM AF Schaefer, Ingo Najavits, Lisa M. TI Clinical challenges in the treatment of patients with posttraumatic stress disorder and substance abuse SO CURRENT OPINION IN PSYCHIATRY LA English DT Article DE comorbidity; posttraumatic stress disorder; substance-use disorder; treatment ID COCAINE-DEPENDENT INDIVIDUALS; TREATMENT-SEEKING ALCOHOLICS; TREATMENT OUTCOMES; PSYCHIATRIC COMORBIDITY; SYMPTOM INTERPLAY; EXPOSURE THERAPY; TRAUMA SURVIVORS; CUE REACTIVITY; PTSD; WOMEN AB Purpose of review The aim of this article is to review the current literature on co-occuring posttraumatic stress disorder and substance-use disorder, with an emphasis on clinical aspects and emerging treatments. Recent findings In clinical populations (focusing on either disorder), about 25-50% have a lifetime dual diagnosis of posttraumatic stress disorder and substance-use disorder. Patients with both disorders have a more severe clinical profile than those with either disorder alone, lower functioning, poorer well being, and worse outcomes across a variety of measures. In recent years, several promising treatment programs have been developed specifically for co-occuring posttraumatic stress disorder and substance-use disorder, with one model having been established as effective thus far. Summary Comorbid posttraumatic stress disorder/substance-use disorder is a frequent diagnosis in clinical populations that severely affects course and outcome. Treatment approaches appropriate for this vulnerable population need to be evaluated further and implemented in routine practice. C1 Univ Med Ctr Hamburg Eppendorf, Dept Psychiat & Psychotherapy, D-20246 Hamburg, Germany. Ctr Interdisciplinary Addict Res, Hamburg, Germany. Harvard Univ, Sch Med, Boston Univ Sch Med, VA Boston,Natl Ctr PTSD, Boston, MA USA. RP Schafer, I (reprint author), Univ Med Ctr Hamburg Eppendorf, Dept Psychiat & Psychotherapy, Martinistr 52, D-20246 Hamburg, Germany. EM i.schaefer@uke.uni-hamburg.de NR 59 TC 48 Z9 49 U1 1 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0951-7367 J9 CURR OPIN PSYCHIATR JI Curr. Opin. Psychiatr. PD NOV PY 2007 VL 20 IS 6 BP 614 EP 618 PG 5 WC Psychiatry SC Psychiatry GA 231JV UT WOS:000250943900016 PM 17921765 ER PT J AU Dorn, M Dzik, W Cserti, C Quagliaroli, R Sullivan, J Xu, S Nayyar, R Sutherland, R Preffer, F AF Dorn, Michelle Dzik, Walter Cserti, Christine Quagliaroli, Robert Sullivan, John Xu, Songyi Nayyar, Rakesh Sutherland, Robert Preffer, Frederic TI Quantitative assessment of CD36 (platelet glycoprotein IV) by flow cytometry: potential role in risk assessment of Plasmodium falciparum malaria SO CYTOMETRY PART B-CLINICAL CYTOMETRY LA English DT Meeting Abstract CT 22nd Annual Meeting of the Clinical-Cytometry-Society CY OCT 07-09, 2007 CL Washington, DC SP Clin Cytometry Soc C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Cambridge, MA 02138 USA. Univ Hlth Network, Toronto, ON, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4949 J9 CYTOM PART B-CLIN CY JI Cytom. Part B-Clin. Cytom. PD NOV PY 2007 VL 72B IS 6 BP 483 EP 484 PG 2 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 227LA UT WOS:000250657000013 ER PT J AU Houghton, L Lindon, CM Freeman, A Morgan, BA AF Houghton, Leslie Lindon, Catherine M. Freeman, Allison Morgan, Bruce A. TI Abortive placode formation in the feather tract of the scaleless chicken embryo SO DEVELOPMENTAL DYNAMICS LA English DT Article DE feather; scaleless; ectodysplasin; pattern formation ID EXPRESSION; MORPHOGENESIS; GROWTH; DIFFERENTIATION; ECTODYSPLASIN; INHIBITION; PRIMORDIA; PATHWAY; CATENIN; PATTERN AB The featherless phenotype of the scaleless mutant provides a model for delineating the process of feather follicle formation. Initial studies established that the mutation affects the epidermis and suggested that epidermis is unable to respond to signals from underlying dermis, or propagate a reciprocal signal. The work presented here demonstrates that scaleless epidermis does indeed respond to the initial inductive signals from dermis, as indicated by the localization of nuclear P-catenin and transient focal expression of genes expressed in the placode of wild-type feather rudiments. In the! sporadic ''escaper'' feathers that form in scaleless, expression of many genes associated with the progression of feather development is comparable to that in wild-type embryos. An exception is the ectodysplasin receptor gene Edar, which is expressed at lower levels in mutant feather buds. These observations suggest that the scaleless mutation impairs the locally augmented expression of Edar required to stabilize the placodal fate and sustain feather development. C1 Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. RP Morgan, BA (reprint author), Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, 149 13th St, Charlestown, MA 02129 USA. EM bruce.morgan@cbrc2.mgh.harvard.edu FU NICHD NIH HHS [R01 HD038465] NR 24 TC 6 Z9 6 U1 0 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD NOV PY 2007 VL 236 IS 11 BP 3020 EP 3030 DI 10.1002/dvdy.21337 PG 11 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 233XK UT WOS:000251123400005 PM 17948257 ER PT J AU Kwan, KM Fujimoto, E Grabher, C Mangum, BD Hardy, ME Campbell, DS Parant, JM Yost, HJ Kanki, JP Chien, CB AF Kwan, Kristen M. Fujimoto, Esther Grabher, Clemens Mangum, Benjamin D. Hardy, Melissa E. Campbell, Douglas S. Parant, John M. Yost, H. Joseph Kanki, John P. Chien, Chi-Bin TI The Tol2kit: A multisite Gateway-based construction kit for Tol2 transposon transgenesis constructs SO DEVELOPMENTAL DYNAMICS LA English DT Article DE transposon; EGFP; mCherry; EMCV IRES; bicistronic; nuclear localization signal ID FISH ORYZIAS-LATIPES; SITE-SPECIFIC RECOMBINATION; GERM-LINE TRANSMISSION; OPEN READING FRAMES; ZEBRAFISH EMBRYOS; GENE-EXPRESSION; FLUORESCENT PROTEIN; XENOPUS-TROPICALIS; MAMMALIAN-CELLS; ORFEOME CLONING AB Transgenesis is an important tool for assessing gene function. In zebrafish, transgenesis has suffered from three problems: the labor of building complex expression constructs using conventional subcloning; low transgenesis efficiency, leading to mosaicism in transient transgenics and infrequent germline incorporation; and difficulty in identifying germline integrations unless using a fluorescent marker transgene. The Tol2kit system uses site-specific recombination-based cloning (multisite Gateway technology) to allow quick, modular assembly of [promoter]-[coding sequence]-[3' tag] constructs in a Tol2 transposon backbone. It includes a destination vector with a cmlc2:EGFP (enhanced green fluorescent protein) transgenesis marker and a variety of widely useful entry clones, including hsp70 and beta-actin promoters; cytoplasmic, nuclear, and membrane-localized fluorescent proteins; and internal ribosome entry sequence-driven EGFP cassettes for bicistronic expression. The Tol2kit greatly facilitates zebrafish transgenesis, simplifies the sharing of clones, and enables large-scale projects testing the functions of libraries of regulatory or coding sequences. C1 Univ Utah, Med Ctr, Dept Neurobiol & Anat, MREB 401, Salt Lake City, UT 84132 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Univ Utah, Dept Oncol Sci, Salt Lake City, UT USA. Univ Utah, Inst Brain, Salt Lake City, UT USA. RP Kwan, KM (reprint author), Univ Utah, Med Ctr, Dept Neurobiol & Anat, MREB 401, 20 North 1900 East, Salt Lake City, UT 84132 USA. EM kristen.kwan@neuro.utah.edu RI Grabher, Clemens/H-2064-2013 FU NCI NIH HHS [2P-01 CA68484-11A1]; NEI NIH HHS [R01 EY12873]; NHLBI NIH HHS [R01 HL66292]; NICHD NIH HHS [5T32 HD07491, T32 HD007491] NR 56 TC 563 Z9 572 U1 6 U2 44 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD NOV PY 2007 VL 236 IS 11 BP 3088 EP 3099 DI 10.1002/dvdy.21343 PG 12 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 233XK UT WOS:000251123400011 PM 17937395 ER PT J AU Medarova, Z Castillo, G Dai, G Bolotin, E Bogdanov, A Moore, A AF Medarova, Zdravka Castillo, Gerardo Dai, Guangping Bolotin, Elijah Bogdanov, Alexei Moore, Anna TI Noninvasive magnetic resonance Imaging of microvascular changes in type 1 diabetes SO DIABETES LA English DT Article ID PANCREATIC-ISLETS; VASCULAR-PERMEABILITY; BLOOD PERFUSION; INFLAMMATION; STREPTOZOTOCIN; VOLUME; MOUSE; INHIBITOR; COPOLYMER; DELIVERY AB OBJECTIVE-The pathogenesis of type 1 diabetes involves autoimmune lymphocytic destruction of insulin-producing beta-cells and metabolic dysregulation. An early biomarker of pancreatic islet damage is islet microvascular dysfunction, and alterations in vascular volume, flow, and permeability have been reported in numerous models of type 1 diabetes. Consequently, the ability to noninvasively monitor the dynamics of the pancreatic microvasculature would aid in early diagnosis and permit the assessment, design, and optimization of individualized therapeutic intervention strategies. RESEARCH DESIGN AND METHODS-Here, we used the long circulating paramagnetic contrast agent, protected graft copolymer (PGC) covalently linked to gadolinium-diethylenetri-aminepentaacetic acid residues (GdDTPAs) labeled with fluorescein isothiocyanate (PGC-GdDTPA-F), for the noninvasive serniquantitative evaluation of vascular changes in a streptozotocin (STZ)-induced mouse model of type 1 diabetes. Diabetic animals and nondiabetic controls were monitored by magnetic resonance imaging (MRI) after injection of PGC-GdDTPA-F. RESULTS-Our findings demonstrated a significantly greater accumulation of PGC-GdDTPA-F in the pancreata of diabetic animals compared with controls. MRI permitted the in vivo serniquantitative assessment and direct visualization of the differential distribution of PGC-GdDTPA-F in diabetic and control pancreata. Ex vivo histology revealed extensive distribution of PGC-GdDTPA-F within the vascular compartment of the pancreas, as well as considerable leakage of the probe into the islet interstitium. By contrast, in nondiabetic controls, PGC-GdDTPA-F was largely restricted to the pancreatic vasculature at the islet periphery. CONCLUSIONS-Based on these observations, we conclude that in the STZ model of type 1 diabetes, changes in vascular volume and permeability associated with early stages of the disease can be monitored noninvasively and semiquantitatively by MRI. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Radiol,Mol Imaging Lab, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Charlestown, MA 02129 USA. PharmaIN Ltd, Seattle, WA USA. Univ Massachusetts, Sch Med, Dept Radiol, Worcester, MA USA. RP Moore, A (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med,Dept Radiol,Mol Imaging Lab, MGH MIT HMS Athinoula A Martinos Ctr Biomed Imagi, Room 2301,Bldg 149 13th St, Charlestown, MA 02129 USA. EM amoore@helix.mgh.harvard.edu FU NIDDK NIH HHS [DK069727] NR 25 TC 24 Z9 26 U1 1 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD NOV PY 2007 VL 56 IS 11 BP 2677 EP 2682 DI 10.2337/db07-0822 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 226VF UT WOS:000250615900005 PM 17682091 ER PT J AU Bentley-Lewis, R Goldfine, AB Green, DE Seely, EW AF Bentley-Lewis, Rhonda Goldfine, Allison B. Green, Dina E. Seely, Ellen W. TI Lactation after normal pregnancy is not associated with blood glucose fluctuations SO DIABETES CARE LA English DT Article ID HUMAN-MILK; WOMEN C1 Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Dept Med, Boston, MA 02115 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. Mt Sinai Med Ctr, Dept Med, Div Endocrinol Diabet & Bone Dis, New York, NY 10029 USA. RP Seely, EW (reprint author), Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Dept Med, 75 Francis St, Boston, MA 02115 USA. EM eseely@partners.org FU NCRR NIH HHS [K23 RR023333, K23 RR023333-01A1]; NIMHD NIH HHS [L32 MD001077-02, L32 MD001077] NR 8 TC 2 Z9 2 U1 1 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD NOV PY 2007 VL 30 IS 11 BP 2792 EP 2793 DI 10.2337/dc07-1243 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 228CI UT WOS:000250704300005 PM 17698611 ER PT J AU Parchman, ML Pugh, JA Wang, CP Romero, RL AF Parchman, Michael L. Pugh, Jacqueline A. Wang, Chen-Pin Romero, Raquel L. TI Glucose control, self-care behaviors, and the presence of the chronic care model in primary care clinics SO DIABETES CARE LA English DT Article; Proceedings Paper CT 33rd Annual Meeting of the North-American-Primary-Care-Research-Group CY OCT 15-18, 2005 CL Quebec City, CANADA SP N Amer Primary Care Res Grp ID IMPROVING PRIMARY-CARE; CHRONIC ILLNESS; DIABETES-MELLITUS; QUALITY IMPROVEMENT; UNITED-STATES; IMPLEMENTATION; COMPLICATIONS; METAANALYSIS; THERAPY; COMPLEX AB OBJECTIVE - The purpose of this study was to examine the relationship between AlC and the extent to which care delivered to patients with type 2 diabetes in primary care clinics is consistent with the chronic care model (CCM), after controlling for self-care behaviors. RESEARCH DESIGN AND METHODS - This was a cross-sectional, observational study of care provided to 618 patients with type 2 diabetes across 20 small, autonomous primary care clinics in South Texas. Subjects completed an exit survey. The medical record was abstracted for AlC values. Clinicians completed the Assessment of Chronic Illness Care (ACIC) survey, a validated measure of the extent to which care delivered is consistent with the CCM. RESULTS - There was a significant relationship between ACIC score and AlC, but this relationship varied according to self-care behavior for exercise and was strongest for those who did not adhere to exercise recommendations: for every 1-point increase in ACIC score, AlC was 0.144% lower (P < 0.001). The relationship between ACIC score and AlC for those who adhered to their diet was similar to that for those who did not, after adjusting for exercise, but the overall level of control was better for those who adhered to their diet. CONCLUSIONS - Characteristics of the primary care clinic where one receives care are an important predictor of glucose control. If resources for implementing the CCM are limited, one might want to focus on clinics with low ACIC scores that serve a population of patients who are sedentary because this population may be likely to realize the most benefit from improved glucose control. C1 S Texas Vet Hlth Care Syst, VERDICT Hlth Serv Res Ctr, San Antonio, TX USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. RP Parchman, ML (reprint author), S Texas Vet Hlth Care Syst 11C6, 7400 Merton Minter Blvd, San Antonio, TX 78229 USA. EM parchman@uthscsa.edu OI Pugh, Jacqueline/0000-0003-4933-141X; Parchman, Michael/0000-0001-7129-2889 FU AHRQ HHS [K08 HS013008-02] NR 39 TC 29 Z9 32 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD NOV PY 2007 VL 30 IS 11 BP 2849 EP 2854 DI 10.2337/dc06-2516 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 228CI UT WOS:000250704300017 PM 17682121 ER PT J AU Hill-Briggs, F Gernmell, L AF Hill-Briggs, Felicia Gernmell, Leigh TI Problem solving in diabetes self-management and control - A systematic review of the literature SO DIABETES EDUCATOR LA English DT Review ID OFFICE-BASED INTERVENTION; DECISION-MAKING; METABOLIC-CONTROL; CONTROLLED-TRIAL; ANCHORED INSTRUCTION; INTENSIVE THERAPY; BEHAVIOR-THERAPY; GLYCEMIC CONTROL; OLDER PATIENTS; ADOLESCENTS AB Purpose The purpose of this systematic review is to assess the published literature on problem solving and its associations with diabetes self-management and control, as the state of evidence exists. Data Sources PubMed, PsychINFO, and ERIC electronic databases were searched for the years 1900 to the present and for English-language articles, and reference lists from included studies were reviewed to capture additional studies. Study Selection Quantitative and qualitative studies that addressed problem solving as a process or strategy for diabetes selfmanagement were included. Fifty-two studies met the criteria for inclusion. Data Extraction Study design, sample characteristics, measures, and results were reviewed. Data Synthesis Thirty-six studies were quantitative; 16 were conceptual or qualitative. Studies were classified as addressing the problem-solving definition/framework, assessment, intervention, or health care professional issues. Conclusions Problem solving is a multidimensional construct encompassing verbal reasoning/rational problem solving, quantitative problem solving, and coping. Aspects of problem solving can be assessed using newly developed diabetesspecific problem-solving measures for children/adolescents and adults. Cross-sectional studies in adults, but not children/adolescents, provide consistent evidence of associations between problem solving and A1C level. Only 25% of problem-solving intervention studies with children/ adolescents and 50% of interventions with adults reported improvement in A1C. Most intervention studies reported an improvement in behaviors, most commonly global adherence in children/adolescents and dietary behavior in adults. Methodological limitations (noninclusion of problem-solving measures, inadequate descriptions of problem-solving interventions, homogenous samples) need to be addressed in future research to clarify the effect of problem solving on diabetes outcomes, identify characteristics of effective interventions, and determine the utility across age and racial/ethnic groups. C1 Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Hlth Behav & Soc, Baltimore, MD USA. VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA. RP Hill-Briggs, F (reprint author), Div Gen Internal Med, 2024 E Monument St,Suite 2-600, Baltimore, MD 21205 USA. EM fbriggs3@jhmi.edu FU NHLBI NIH HHS [1 K01 HL076644] NR 64 TC 59 Z9 61 U1 2 U2 23 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0145-7217 J9 DIABETES EDUCATOR JI Diabetes Educ. PD NOV-DEC PY 2007 VL 33 IS 6 BP 1032 EP 1050 DI 10.1177/0145721707308412 PG 19 WC Endocrinology & Metabolism; Public, Environmental & Occupational Health SC Endocrinology & Metabolism; Public, Environmental & Occupational Health GA 238LL UT WOS:000251449000011 PM 18057272 ER PT J AU Nathan, DM Turgeon, H Regan, S AF Nathan, D. M. Turgeon, H. Regan, S. TI Relationship between glycated haemoglobin levels and mean glucose levels over time SO DIABETOLOGIA LA English DT Article DE diabetes; diabetes management; chronic glycaemia; glycated haemoglobin ID BLOOD-GLUCOSE; GLYCOSYLATED HEMOGLOBIN; NONDIABETIC SUBJECTS; DIABETES-MELLITUS; PLASMA-GLUCOSE; GLYCEMIA; GLYCOHEMOGLOBIN; VARIABILITY; ACCURACY; GHB AB Aims/hypothesis HbA(1c), expressed as the percentage of adult haemoglobin that is glycated, is the most widely used measure of chronic glycaemia. Achieving near-normal HbA(1c) levels has been shown to reduce long-term complications and the HbA(1c) assay is recommended to determine whether treatment is adequate and to guide adjustments. However, daily adjustments of therapy are guided by capillary glucose levels (mmol/l). We determined the relationship between an accurate measure of mean glucose levels over time and the HbA(1c) level, and whether HbA(1c) can be expressed in the same units as self-monitoring results. Methods Twenty-two participants with diabetes and three non-diabetic participants were included in this longitudinal observational study. Mean glucose levels were measured by continuous glucose monitoring (CGM), which measures interstitial glucose levels every 5 min, for 12 weeks. Capillary measurements were obtained four times per day to confirm the accuracy of CGM. HbA1c was measured at baseline and every 4 weeks. Results The HbA1c results at weeks 8 and 12 correlated strongly (r=0.90) with the CGM results during the preceding 8 and 12 weeks. A curvilinear (exponential) relationship and a linear regression captured the relationship with similarly high correlations, which allowed transformation of HbA(1c) values to a calculated mean glucose level. Conclusions and interpretation HbA(1c) correlates closely with a complete measure of average glycaemia over the preceding 8-12 weeks. The translation of HbA(1c) to an average glucose level for reporting and management purposes is feasible. C1 Massachusetts Gen Hosp, Ctr Diabet, Dept Biostat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. RP Nathan, DM (reprint author), Massachusetts Gen Hosp, Ctr Diabet, Dept Biostat, 50 Staniford St,Suite 340, Boston, MA 02114 USA. EM dnathan@Partners.org NR 25 TC 131 Z9 137 U1 2 U2 14 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0012-186X J9 DIABETOLOGIA JI Diabetologia PD NOV PY 2007 VL 50 IS 11 BP 2239 EP 2244 DI 10.1007/s00125-007-0803-0 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 216ZI UT WOS:000249917200003 PM 17851648 ER PT J AU Leung, FW Chan, CC AF Leung, Felix W. Chan, Chi Chung TI Involvement of alpha(2)-adrenoceptors in the gastric protective effect of nitroglycerin against acidified ethanol-induced mucosal injury SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE nitroglycerin; gastric volume; gastric mucosal injury; acidified ethanol; yohimbine ID INTRAGASTRIC NICOTINE PROTECTION; OXIDE-RELEASING ASPIRIN; NITRIC-OXIDE; RELAXING FACTOR; RAT STOMACH; DAMAGE; CYTOPROTECTION; MECHANISM; PROSTAGLANDIN-E2; GASTROPROTECTION AB Clinical observations reveal that alcohol intake is associated with an increase in upper gastrointestinal hemorrhage requiring hospitalization and that nitroglycerin or long-acting nitrates lower this risk. Nitroglycerin, a gastric vasodilator that can increase gastric fluid volume, protects the rodent stomach against damage, including that caused by 70% ethanol. Blockade of alpha(2)-adrenoceoptors attenuates gastric protection by intragastric nicotine against 40% ethanol. We tested the hypothesis that the protective effect of nitroglycerin is mediated by an increase in gastric fluid volume and alpha(2)-adrenoceoptors. Nitroglycerin, 5 mg/kg, vehicle, or acidified ethanol was administered intragastrically. In study 1 acidified ethanol-induced mucosal injury was measured. In study 2 the effect of increasing gastric volume (1 ml/kg) on mucosal injury was assessed. In study 3 the effect of yohimbine (alpha(2)-adrenoceoptor antagonist), 5 mg/kg subcutaneously, on the nitroglycerein-mediated protective effect was determined. Results showed that nitroglycerin significantly attenuated the number and length of mucosal lesions induced by acidified ethanol. Increase in gastric fluid volume by exogenously administered saline did not alter the protective effect. Yohimbine blocked the nitroglycerin-mediated protection. These experimental data are consistent with the observation that nitrates lower the risk of ethanol-induced gastrointestinal complications. alpha(2)-Adrenoceoptors are responsible in part for the protective effect of nitroglycerin. C1 Sepulveda Ambulatory Care Ctr, Div Gastroenterol, Sepulveda, CA 91343 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90024 USA. VA Greater Los Angeles Healthcare Syst, Sepulveda Ambulatory Care Ctr, Res & Med Serv, Los Angeles, CA USA. Merck Frosst Ctr Therapeut Res, Dept Pharmacol, Kirkland, PQ, Canada. RP Leung, FW (reprint author), Sepulveda Ambulatory Care Ctr, Div Gastroenterol, 111G,16111 Plummer St, Sepulveda, CA 91343 USA. EM felix.leung@va.gov NR 33 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD NOV PY 2007 VL 52 IS 11 BP 3070 EP 3074 DI 10.1007/s10620-006-9692-1 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 216ZJ UT WOS:000249917400028 PM 17394070 ER PT J AU Tran, T Hampel, H Qureshi, WA Shaib, Y AF Tran, Thomas Hampel, Howard Qureshi, Waqar A. Shaib, Yasser TI Successful endoscopic management of bronchobiliary fistula due to radiofrequency ablation SO DIGESTIVE DISEASES AND SCIENCES LA English DT Article DE bronchobiliary fistula; radiofrequency ablation; hepatic iminodiacetic acid; endoscopic retrograde cholangiopancreatography; endoscopic sphincterectomy; biliary stent ID THORACOBILIARY FISTULA; CHOLANGIOGRAPHY C1 Michael E DeBakey Vet Affairs Med Ctr, Gastroenterol Sect, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. RP Tran, T (reprint author), Michael E DeBakey Vet Affairs Med Ctr, Gastroenterol Sect, 2002 Holcombe Blvd 152, Houston, TX 77030 USA. EM tungthomastran@yahoo.com NR 15 TC 5 Z9 6 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0163-2116 J9 DIGEST DIS SCI JI Dig. Dis. Sci. PD NOV PY 2007 VL 52 IS 11 BP 3178 EP 3180 DI 10.1007/s10620-006-9331-x PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 216ZJ UT WOS:000249917400050 PM 17638080 ER PT J AU Johnson, B AF Johnson, B. TI Biomarkers of lung cancer response to EGFR-TKI SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT Annual Meeting of the EORTC-NCI-ASCO on Molecular Markers in Cancer CY NOV 15-17, 2007 CL Brussels, BELGIUM SP EORTC, NCI, ASCO C1 [Johnson, B.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 2 Z9 2 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 2007 VL 5 IS 8 BP 14 EP 15 DI 10.1016/S1359-6349(08)70028-4 PG 2 WC Oncology SC Oncology GA 242DX UT WOS:000251705800024 ER PT J AU Gandhi, L Exarhopoulos, A Johnson, BE Moses, MA AF Gandhi, L. Exarhopoulos, A. Johnson, B. E. Moses, M. A. TI Assessing the utility of matrix-degrading enzymes as a biomarker for disease status and therapeutic efficacy in lung cancer SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT Annual Meeting of the EORTC-NCI-ASCO on Molecular Markers in Cancer CY NOV 15-17, 2007 CL Brussels, BELGIUM SP EORTC, NCI, ASCO C1 [Gandhi, L.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Exarhopoulos, A.] Childrens Hosp, Boston, MA USA. Harvard Med Sch, Dana Farber Canc Inst, Boston, MA USA. [Moses, M. A.] Harvard Med Sch, Childrens Hosp, 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 2007 VL 5 IS 8 BP 24 EP 24 DI 10.1016/S1359-6349(08)70055-7 PG 1 WC Oncology SC Oncology GA 242DX UT WOS:000251705800051 ER PT J AU Bonanno, GA Colak, DM Keltner, D Shiota, MN Papa, A Noll, JG Putnam, FW AF Bonanno, George A. Colak, Deniz M. Keltner, Dacher Shiota, Michelle N. Papa, Anthony Noll, Jennie G. Putnam, Frank W. TI Context matters: The benefits and costs of expressing positive emotion among survivors of childhood sexual abuse SO EMOTION LA English DT Review DE laughter; smiling; social adjustment; childhood sexual abuse; positive emotion ID DEVELOPMENTAL PSYCHOPATHOLOGY PERSPECTIVE; FACIAL EXPRESSIONS; EMERGING ADULTHOOD; DISSOCIATIVE EXPERIENCES; SOCIAL MALADJUSTMENT; CONJUGAL BEREAVEMENT; INFANTS RESPONSES; RESILIENCE; LAUGHTER; SMILES AB Positive emotions promote adjustment to aversive life events. However, evolutionary theory and empirical research on trauma disclosure suggest that in the context of stigmatized events, expressing positive emotions might incur social costs. To test this thesis, the authors coded genuine (Duchenne) smiling and laughter and also non-Duchenne smiling from videotapes of late-adolescent and young adult women, approximately half with documented histories of childhood sexual abuse (CSA), as they described the most distressing event of their lives. Consistent with previous studies, genuine positive emotional expression was generally associated with better social adjustment two years later. However, as anticipated, CSA survivors who expressed positive emotion in the context of describing a past CSA experience had poorer long-term social adjustment, whereas CSA survivors who expressed positive emotion while describing a nonabuse experience had improved social adjustment. These findings suggest that the benefits of positive emotional expression may often be context specific. C1 Columbia Univ, Dept Counseling & Clin Psychol, Teachers Coll, New York, NY 10027 USA. Univ Calif Berkeley, Berkeley, CA 94720 USA. VA Boston Healthcare Syst, Boston, MA USA. Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA. Univ So Calif, Los Angeles, CA 90089 USA. RP Bonanno, GA (reprint author), Columbia Univ, Dept Counseling & Clin Psychol, Teachers Coll, 525 W 120th St,Box 218, New York, NY 10027 USA. EM gab38@columbia.edu RI Shiota, Michelle/C-3987-2008 FU NIMH NIH HHS [MH 48330] NR 117 TC 25 Z9 25 U1 0 U2 11 PU AMER PSYCHOLOGICAL ASSOC/EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1528-3542 J9 EMOTION JI Emotion PD NOV PY 2007 VL 7 IS 4 BP 824 EP 837 DI 10.1037/1528-3542.7.4.824 PG 14 WC Psychology, Experimental SC Psychology GA 232WS UT WOS:000251052000015 PM 18039052 ER PT J AU Seminara, SB AF Seminara, Stephanie B. TI Converging at puberty's hub SO ENDOCRINOLOGY LA English DT Editorial Material ID GONADOTROPIN-SECRETION; RHESUS-MONKEY; HORMONE; GPR54; HYPOTHALAMUS; STIMULATION; RECEPTOR; PEPTIDE; ONSET; ACID C1 Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. RP Seminara, SB (reprint author), Massachusetts Gen Hosp, Reprod Endocrine Unit, Bartlett Hall Extens 505,55 Fruit St, Boston, MA 02114 USA. EM seminara.stephanie@mgh.harvard.edu NR 17 TC 5 Z9 5 U1 1 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD NOV PY 2007 VL 148 IS 11 BP 5145 EP 5146 DI 10.1210/en.2007-0953 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 224JT UT WOS:000250444000003 PM 17940187 ER PT J AU Tomson, T Battino, D French, J Harden, C Holmes, L Morrow, J Robert-Gnansia, E Scheuerle, A Vajda, F Wide, K Gordon, J AF Tomson, Torbjorn Battino, Dina French, Jacqueline Harden, Cynthia Holmes, Lewis Morrow, Jim Robert-Gnansia, Elisabeth Scheuerle, Angela Vajda, Frank Wide, Katarina Gordon, Jacki CA ETDP Work Grp TI Antiepileptic drug exposure and major congenital malformations: The role of pregnancy registries SO EPILEPSY & BEHAVIOR LA English DT Article DE epilepsy; pregnancy; antiepileptic drugs; malformations; teratogenicity ID UK-EPILEPSY; EXPERIENCE; INFANTS AB The use of antiepileptic drugs (AEDs) in pregnancy is associated with an increased risk of fetal malformations. Although it is known that AEDs may differ with respect to the type of malformations they can induce, earlier studies have generally lacked the power to demonstrate differences between AEDs in their overall teratogenic potential. Furthermore, there is an urgent need to assess the clinical teratogenic potential of the newer-generation AEDs. Epilepsy and pregnancy registries have been established to provide such information, which is essential for the rational management of women with epilepsy with childbearing potential. The registries also provide opportunities for additional studies of seizures observed during pregnancy and labor and, with the enrolled woman's consent, for separate studies on cognititve outcomes and pharmacogenetics. Although most are prospective, the existing registries vary somewhat in design, which needs to be considered when their results are compared. Some registries are driven by pharmaceutical companies (often compelled by national or international drug licensing agencies) and provide data on pregnancy outcome related to the sponsor's own product. Others are organized by independent research groups and are potentially more useful in that they publish comparative data. This review provides a critical discussion and comparison of important methodological aspects of AED and pregnancy registries along with a summary of results published so far. (C) 2007 Elsevier Inc. All rights reserved. C1 Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden. Neurol Inst Carlo Besta, Milan, Italy. Univ Penn, Philadelphia, PA 19104 USA. Weill Cornell Med Coll, Dept Neurol, New York, NY USA. MassGen Hosp Children, Genet Unit, Boston, MA USA. Royal Grp Hosp, Dept Neurol, Belfast, Antrim, North Ireland. RTH Laennec, Fac Med, REMERA, Lyon, France. Tesserae Genet, Dallas, TX USA. Monash Med Ctr, Melbourne, Vic, Australia. Univ Melbourne, Melbourne, Vic, Australia. Karolinska Inst, Dept Clin Sci, Div Pediat, Stockholm, Sweden. Epilepsy Therapy Dev Project, Reston, VA USA. RP Tomson, T (reprint author), Karolinska Univ Hosp, Dept Neurol, SE-17176 Stockholm, Sweden. EM torbjorn.tomson@karolinska.se RI French, Jacqueline/G-6795-2013; OI French, Jacqueline/0000-0003-2242-8027; Wide, Katarina/0000-0003-3024-0657 NR 15 TC 22 Z9 22 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 1525-5050 J9 EPILEPSY BEHAV JI Epilepsy Behav. PD NOV PY 2007 VL 11 IS 3 BP 277 EP 282 DI 10.1016/j.yebeh.2007.08.015 PG 6 WC Behavioral Sciences; Clinical Neurology; Psychiatry SC Behavioral Sciences; Neurosciences & Neurology; Psychiatry GA 233CK UT WOS:000251067800006 PM 17996635 ER PT J AU Parikh, NI Gona, P Larson, MG Wang, TJ Newton-Cheh, C Levy, D Benjamin, EJ Kannel, WB Vasan, RS AF Parikh, Nisha I. Gona, Philimon Larson, Martin G. Wang, Thomas J. Newton-Cheh, Christopher Levy, Daniel Benjamin, Emelia J. Kannel, William B. Vasan, Ramachandran S. TI Plasma renin and risk of cardiovascular disease and mortality: the Framingham Heart Study SO EUROPEAN HEART JOURNAL LA English DT Article DE renin; cardiovascular disease; hypertension; all-cause mortality; epidemiology ID LEFT-VENTRICULAR DYSFUNCTION; MYOCARDIAL-INFARCTION; RANDOMIZED TRIAL; TISSUE ANGIOTENSIN; BLOOD-PRESSURE; ALDOSTERONE; HYPERTENSION; PATHOGENESIS; EVENTS; ATTACK AB Aims Previous studies relating plasma renin to cardiovascular disease (CVD) and mortality yielded conflicting results. We related plasma renin to incidence of CVD and mortality in 3408 individuals (mean age 59; 53% women) and in a hypertensive subset (n = 1413). Methods and results On follow-up (mean 7.1 years), 176 participants (122 hypertensives) developed CVD and 215 individuals (127 hypertensives) died. Overall, log-renin was associated with mortality [multivariabte-adjusted hazards ratio (HR) per SD increment: in whole sample, 1.14, 95% confidence interval (Cl) 1.00-1.30, P=0.046; hypertensives, 1.16, 95% Cl 1.00-1.35, P=0.046], but relations varied over time (P < 0.02). Log-renin was associated with mortality at 2.5 years of follow-up (HR per SD increment: whole sample at 2.5 years, 1.23, 95% Cl 1.04-1.45; hypertensives at 2 years, 1.28, 95% Cl 1.06-1.54), but not during longer follow-up (HR per SD increment at 5 years: whole sample, 1.02, 95% Cl 0.80-1.29; hypertensives, 0.98, 95% Cl 0.74-1.30). The time-dependent relation of renin and mortality risk was maintained upon excluding participants with prevalent CVD. Renin was not associated with CVD incidence (HR per SD increment log-renin: whole sample, 0.99, 95% Cl 0.85-1.14; hypertensives, 0.96, 95% Cl 0.82-1.12). Conclusion Higher plasma renin was associated with greater short-term mortality but not with CVD incidence in the community. C1 Boston Univ, Sch Med, Framingham Heart Study, Framingham, MA 01702 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. NHLBI, Bethesda, MD 20892 USA. Boston Univ, Sch Med, Sect Prevent Med, Boston, MA 02118 USA. Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02118 USA. RP Vasan, RS (reprint author), Boston Univ, Sch Med, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM vasan@bu.edu OI Larson, Martin/0000-0002-9631-1254; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [2K24HL04334, K23HL074077, N01-HC-25195, R01HL67288] NR 39 TC 40 Z9 40 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 2007 VL 28 IS 21 BP 2644 EP 2652 DI 10.1093/eurheartj/ehm399 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 238ZA UT WOS:000251485900018 PM 17895253 ER PT J AU Alt, FW AF Alt, Frederick W. TI From gene amplification to V(D)J recombination and back: A personal account of my early years in B cell biology SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE allelic exclusion; B cells; DNA repair; Novartis prize; V(D)J recombination ID MURINE LEUKEMIA-VIRUS; LIGHT-CHAIN GENES; MU-HEAVY-CHAINS; DEPENDENT PROTEIN-KINASE; CYTIDINE DEAMINASE AID; STRAND BREAK REPAIR; 2 MESSENGER-RNAS; IMMUNOGLOBULIN-MU; ALLELIC EXCLUSION; DNA-REPAIR AB I have been invited to write a short historical feature in the context of being a co-recipient with Klaus Raiewsky and Fritz Melchers of the 2007 Novartis Prize in Basic Immunology that was given in the general area of the molecular biology of B cells. In this feature, I cover the main points of the short talk that I presented at the Award Ceremony at the International Immunology Congress in Rio de Janeiro, Brazil. This talk focused primarily on the work and people involved early on in generating the models and ideas that have formed the basis for my ongoing efforts in the areas of V(D)J. recombination and B cell development. C1 Childrens Hosp, Howard Hughes Med Inst, Immune Dis Inst, Dept Genet, Boston, MA 02115 USA. RP Alt, FW (reprint author), Childrens Hosp, Howard Hughes Med Inst, 300 Longwood Ave, Boston, MA 02115 USA. EM Alt@enders.tch.harvard.edu FU Howard Hughes Medical Institute NR 79 TC 0 Z9 0 U1 0 U2 2 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD NOV PY 2007 VL 37 SU 1 BP S138 EP S147 DI 10.1002/eji.2007378481 PG 10 WC Immunology SC Immunology GA 235NB UT WOS:000251239900016 PM 17972338 ER PT J AU Rajewsky, K AF Rajewsky, Klaus TI From a dream to reality SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE antigen bridge; conditional gene targeting; Cre zoo; T-B cell collaboration ID TARGETED DISRUPTION; MAMMALIAN-CELLS; MEMBRANE EXON; GENE; IMMUNOGLOBULIN; MOUSE; MICE; RECOMBINATION; MUTAGENESIS; SELECTION C1 Harvard Med Sch, CBR Inst Biomed Res, Boston, MA 02115 USA. RP Rajewsky, K (reprint author), Harvard Med Sch, CBR Inst Biomed Res, Boston, MA 02115 USA. EM rajewsky@cbr.med.harvard.edu NR 24 TC 4 Z9 4 U1 0 U2 1 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD NOV PY 2007 VL 37 SU 1 BP S134 EP S137 DI 10.1002/eji.200737819 PG 4 WC Immunology SC Immunology GA 235NB UT WOS:000251239900015 PM 17972357 ER PT J AU Rouvas, AA Ladas, ID Papakostas, TD Moschos, MM Vergados, I AF Rouvas, A. A. Ladas, I. D. Papakostas, T. D. Moschos, M. M. Vergados, I. TI Intravitreal ranibizumab in a patient with choroidal neovascularization secondary to multiple evanescent white dot syndrome SO EUROPEAN JOURNAL OF OPHTHALMOLOGY LA English DT Article DE choroidal neovascularization; high-speed ICG; multiple evanescent white dot syndrome; white spots; ranibizumab AB PURPOSE. To report the effect of a single intravitreal injection of ranibizumab in a patient with choroidal neovascularization (CNV) secondary to multiple evanescent white dot syndrome (MEWDS). METHODS. A 65-year-old woman with visual acuity (VA) 20/40, mild vitreous inflammation, optic disc edema, and white deep retinal round lesions in the right eye underwent fluorescein angiography, indocyanine green angiography, and optical coherence tomography. The diagnosis of MEWDS with peripapillary CNV was made and a single injection of ranibizumab (0.5 mg) was administered. RESULTS. At the 6-month follow-up visit, the VA in the right eye was 20/20, the CNV completely regressed, and the MEWDS findings disappeared. CONCLUSIONS. Intravitreal ranibizumab appears to be a safe and effective treatment option in cases of CNV secondary to MEWDS, resulting in fast resolution of the macular edema and regression of the CNV. On the other hand, it is unclear whether the administration of ranibizumab contributed to a prompt regression of MEWDS. C1 [Rouvas, A. A.; Vergados, I.] Univ Athens, Sch Med, Dept Ophthalmol 2, Athens, Greece. [Ladas, I. D.; Moschos, M. M.] Univ Athens, Sch Med, Dept Ophthalmol 1, Athens, Greece. [Papakostas, T. D.] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Boston, MA USA. EM t_papakostas@yahoo.com NR 10 TC 9 Z9 10 U1 0 U2 1 PU WICHTIG EDITORE PI MILAN PA 72/74 VIA FRIULI, 20135 MILAN, ITALY SN 1120-6721 J9 EUR J OPHTHALMOL JI Eur. J. Ophthalmol. PD NOV-DEC PY 2007 VL 17 IS 6 BP 996 EP 999 PG 4 WC Ophthalmology SC Ophthalmology GA 265UO UT WOS:000253386800023 PM 18050132 ER PT J AU Yamashita, T Akita, H Astner, S Miyakawa, M Lerner, EA Gonzalez, S AF Yamashita, Toyonobu Akita, Hirotaka Astner, Susanne Miyakawa, Michio Lerner, Ethan Arthur Gonzalez, Salvador TI In vivo assessment of pigmentary and vascular compartments changes in UVA exposed skin by reflectance-mode confocal microscopy SO EXPERIMENTAL DERMATOLOGY LA English DT Article DE erythema; melanin; reflectance-mode confocal microscopy; tanning; UVA ID OPTICAL COHERENCE TOMOGRAPHY; SCANNING LASER MICROSCOPY; ULTRAVIOLET-RADIATION; DISTRIBUTION PATTERN; MALIGNANT-MELANOMA; HUMAN MELANOCYTES; INDUCED ERYTHEMA; MECHANISMS; HISTOLOGY; LIGHT AB Exposure of the skin to ultraviolet A (UVA) results in various biological responses, skin-colour changes being among the major ones. Although intense research has been performed on UVA-induced pigmentation and vascular changes, the process of skin-colour changes after UVA irradiation remains unclear. For a better understanding of the UVA tanning mechanism, we here performed a human study in 27 healthy volunteers with skin phototype (SPT) II to VI. After a single UVA exposure to inner forearm, the skin sites were imaged using reflectance-mode confocal microscopy (RCM), for analysis of melanin and vascular changes. Punch biopsies were also taken from the UVA-exposed or non-exposed sites for histological examination. Skin sections were stained with Fontana-Masson and evaluated by a sensitive tyrosinase assay for comparison with RCM images. Furthermore, the effect of blood flow on skin-colour changes was evaluated visually after administration of an intradermal anesthesia of lidocaine with or without epinephrine. Our RCM analysis showed dendritic melanocytes and a different melanin distribution in the epidermal layer, clearly visible 1 week after the UVA exposure in subjects of SPT V which were supported by histological examination. However, no melanin distribution pattern changes were apparent immediately after the exposure, while RCM images showed accelerated capillary flow patterns. The restriction of this UVA induced-accelerated blood flow by epinephrine inhibited partially or completely the immediate pigment darkening and delayed tanning. These in vivo studies confirmed that vascular change is an important factor for the development of the immediate pigment darkening and delayed tanning. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA USA. Niigata Univ, Ctr Transdisciplinary Res, Niigata, Japan. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr, Boston, MA USA. RP Yamashita, T (reprint author), Shiseido Res Ctr, Tsuzuki Ku, 2-2-1 Hayabuchi, Yokohama, Kanagawa 2248558, Japan. EM toyonobu.yamashita@to.shiseido.co.jp NR 34 TC 16 Z9 18 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0906-6705 J9 EXP DERMATOL JI Exp. Dermatol. PD NOV PY 2007 VL 16 IS 11 BP 905 EP 911 DI 10.1111/j.1600-0625.2007.00604.x PG 7 WC Dermatology SC Dermatology GA 219IU UT WOS:000250078900004 PM 17927573 ER PT J AU Wilson, AC Meethal, SV Bowen, RL Atwood, CS AF Wilson, Andrea C. Meethal, Sivan Vadakkadath Bowen, Richard L. Atwood, Craig S. TI Leuprolide acetate: a drug of diverse clinical applications SO EXPERT OPINION ON INVESTIGATIONAL DRUGS LA English DT Review DE Alzheimer's disease; central precocious puberty; contraception; endometriosis; functional bowel disease; GnRH analog; gonadotropin-releasing hormone; gonadotropin-releasing hormone receptor; in vitro fertilization; leuprolide acetate; polycystic ovary syndrome; premenstrual syndrome; prostate cancer; short stature; uterine leiomyomata ID GONADOTROPIN-RELEASING-HORMONE; CENTRAL PRECOCIOUS PUBERTY; ADVANCED PROSTATE-CANCER; POLYCYSTIC-OVARY-SYNDROME; FUNCTIONAL BOWEL-DISEASE; RAT MAMMARY-TUMORS; IN-VITRO FERTILIZATION; LONG-TERM TREATMENT; LUTEINIZING-HORMONE; DEPOT LEUPROLIDE AB Leuprolide acetate is a synthetic nonapeptide that is a potent gonadotropin-releasing hormone receptor (GnRHR) agonist used for diverse clinical applications, including the treatment of prostate cancer, endometriosis, uterine fibroids, central precocious puberty and in vitro fertilization techniques. As its basic mechanism of action, leuprolide acetate suppresses gonadotrope secretion of luteinizing hormone and follicle-stimulating hormone that subsequently suppresses gonadal sex steroid production. In addition, leuprolide acetate is presently being tested for the treatment of Alzheimer's disease, polycystic ovary syndrome, functional bowel disease, short stature, premenstrual syndrome and even as an alternative for contraception. Mounting evidence suggests that GnRH agonist suppression of serum gonadotropins may also be important in many of the clinical applications described above. Moreover, the presence of GnRHR in a multitude of non-reproductive tissues including the recent discovery of GnRHR expression in the hippocampi and cortex of the human brain indicates that GnRH analogs such as leuprolide acetate may also act directly via tissue GnRHRs to modulate (brain) function. Thus, the molecular mechanisms underlying the therapeutic effect of GnRH analogs in the treatment of these diseases may be more complex than originally thought. These observations also suggest that the potential uses of GnRH analogs in the modulation of GnRH signaling and treatment of disease has yet to be fully realized. C1 Univ Wisconsin, William S Middleton Mem Vet Adm Hosp, Educ Clin Ctr, Dept Med Geriatr Res, Madison, WI 53705 USA. RP Atwood, CS (reprint author), Univ Wisconsin, William S Middleton Mem Vet Adm Hosp, Educ Clin Ctr, Dept Med Geriatr Res, 2500 Overlook Terrace, Madison, WI 53705 USA. EM csa@medicine.wisc.edu NR 127 TC 48 Z9 50 U1 1 U2 5 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1354-3784 EI 1744-7658 J9 EXPERT OPIN INV DRUG JI Expert Opin. Investig. Drugs PD NOV PY 2007 VL 16 IS 11 BP 1851 EP 1863 DI 10.1517/13543784.16.11.1851 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 233UY UT WOS:000251117000009 PM 17970643 ER PT J AU Chi, A Norden, AD Wen, PY AF Chi, Andrew Norden, Andrew D. Wen, Patrick Y. TI Inhibition of angiogenesis and invasion in malignant gliomas SO EXPERT REVIEW OF ANTICANCER THERAPY LA English DT Review DE angiogenesis; glioblastoma; invasion; malignant glioma; targeted molecular therapy ID ENDOTHELIAL-GROWTH-FACTOR; TYROSINE KINASE INHIBITOR; PHASE-II TRIAL; HIGH-GRADE GLIOMAS; PLASMINOGEN-ACTIVATOR RECEPTOR; HUMAN GLIOBLASTOMA CELLS; FOCAL ADHESION KINASE; MATRIX-METALLOPROTEINASE INHIBITORS; METASTATIC COLORECTAL-CANCER; NEWLY-DIAGNOSED GLIOBLASTOMA AB Malignant gliomas confer a dismal prognosis. As the molecular events that underlie tumor angiogenesis are elucidated, angiogenesis inhibition is emerging as a promising therapy for recurrent and newly diagnosed tumors. Data from animal studies suggest that angiogenesis inhibition may promote an invasive phenotype in tumor cells. This may represent an important mechanism of resistance to antiangiogenic therapies. Recent studies have begun to clarify the mechanisms by which glioma cells detach from the tumor mass, remodel the extracellular matrix and infiltrate normal brain. An array of potential therapeutic targets exists. Combination therapy with antiangiogenic and novel anti-invasion agents is a promising approach that may produce a synergistic antitumor effect and a survival benefit for patients with these devastating tumors. C1 Brigham & Womens Hosp, Dept Neurol, Dana Farber Brigham & Womens Canc Ctr, Div Neurooncol,Ctr Neurooncol, Boston, MA 02115 USA. RP Wen, PY (reprint author), Brigham & Womens Hosp, Dept Neurol, Dana Farber Brigham & Womens Canc Ctr, Div Neurooncol,Ctr Neurooncol, SW430D,44 Binney St, Boston, MA 02115 USA. EM achi@partners.org; anorden@partners.org; pwen@partners.org NR 291 TC 46 Z9 47 U1 0 U2 3 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 2007 VL 7 IS 11 BP 1537 EP 1560 DI 10.1586/14737140.7.11.1537 PG 24 WC Oncology SC Oncology GA 238JS UT WOS:000251444300012 PM 18020923 ER PT J AU May, A Wang, TJ AF May, Abigail Wang, Thomas J. TI Evaluating the role of biomarkers for cardiovascular risk prediction: focus on CRP, BNP and urinary microalbumin SO EXPERT REVIEW OF MOLECULAR DIAGNOSTICS LA English DT Review DE biomarker; B-type natriuretic peptide; cardiovascular risk; C-reactive protein; urinary microalbumin ID C-REACTIVE PROTEIN; CORONARY-HEART-DISEASE; BRAIN NATRIURETIC PEPTIDE; EMERGENCY-DEPARTMENT PRIDE; BODY-MASS INDEX; OUTCOMES PREVENTION EVALUATION; ACUTE MYOCARDIAL-INFARCTION; CLINICALLY HEALTHY-SUBJECTS; AORTIC ENDOTHELIAL-CELLS; DIABETES-MELLITUS AB Cardiovascular disease is a significant cause of morbidity and mortality, making cardiovascular prevention an important public health goal. The use of cardiac biomarkers represents a potential, noninvasive method to identify asymptomatic individuals who are most likely to develop cardiovascular disease. Several known biomarkers predict cardiovascular risk above and beyond conventional risk factors. Nonetheless, available evidence suggests that current biomarkers do not have sufficient sensitivity or specificity to justify widespread use for cardiovascular risk prediction. New developments in molecular biology and genetics may allow the identification of additional biomarkers, likely acting via different pathways, to achieve this goal. C1 Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Harvard Med Sch, Dept Internal Med, Boston, MA USA. RP Wang, TJ (reprint author), Massachusetts Gen Hosp, Div Cardiol, GRB-800, 55 Fruit Str, Boston, MA 02114 USA. EM tjwang@partners.org FU NHLBI NIH HHS [K23-HL-074077, R01-HL-083197] NR 127 TC 15 Z9 15 U1 0 U2 2 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7159 J9 EXPERT REV MOL DIAGN JI Expert Rev. Mol. Diagn. PD NOV PY 2007 VL 7 IS 6 BP 793 EP 804 DI 10.1586/14737159.7.6.793 PG 12 WC Pathology SC Pathology GA 239LW UT WOS:000251520800011 PM 18020909 ER PT J AU Harrington, L Srikanth, CV Antony, R Shi, HN Cherayil, BJ AF Harrington, Lynne Srikanth, Chittur V. Antony, Reuben Shi, Hai Ning Cherayil, Bobby J. TI A role for natural killer cells in intestinal inflammation caused by infection with Salmonella enterica serovar Typhimurium SO FEMS IMMUNOLOGY AND MEDICAL MICROBIOLOGY LA English DT Article DE Salmonella; NK cells; intestinal inflammation ID RECEPTOR-GAMMA CHAIN; NON-TYPHOIDAL SALMONELLOSIS; INNATE IMMUNE-RESPONSE; IFN-GAMMA; T-CELLS; LISTERIA-MONOCYTOGENES; NEUTROPHIL INFLUX; INTERFERON-GAMMA; NK-CELLS; MICE AB Acute gastroenteritis caused by Salmonella infection is a significant public health problem. Using a mouse model of this condition, the authors demonstrated previously that the cytokine gamma interferon (IFN-gamma) is required for a normal intestinal inflammatory response to the pathogen. In the present study, these experiments are extended to show that natural killer (NK) cells constitute an early source of intestinal IFN-gamma during Salmonella infection, and that these cells have a significant impact on intestinal inflammation. It was found that infection of mice with Salmonella increased both intestinal IFN-gamma production and the numbers of NK cells in the intestine and mesenteric lymph nodes. NK cells, along with other types of lymphocytes, produced IFN-gamma in response to the bacteria in vitro, while antibody-mediated depletion of NK cells in vivo resulted in a significant reduction in Salmonella-induced intestinal IFN-gamma expression. In a mouse strain lacking NK cells and T and B lymphocytes, intestinal production of IFN-gamma and Salmonella-induced intestinal inflammation were both significantly decreased compared with a strain deficient only in T and B cells. The authors' observations point to an important function for NK cells and NK-derived IFN-gamma in regulating the intestinal inflammatory response to Salmonella. C1 Massachusetts Gen Hosp, Pediat Gastroenterol Unit, Mucosal Immunol Lab, Charlestown, MA 02129 USA. RP Cherayil, BJ (reprint author), Massachusetts Gen Hosp, Pediat Gastroenterol Unit, Mucosal Immunol Lab, Bldg 114,16th St, Charlestown, MA 02129 USA. EM cherayil@helix.mgh.harvard.edu FU NIAID NIH HHS [R21 AI065619, AI-065619, AI-48815, R01 AI048815]; NIDDK NIH HHS [P30 DK040561, P30 DK040561-12] NR 42 TC 29 Z9 31 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0928-8244 J9 FEMS IMMUNOL MED MIC JI FEMS Immunol. Med. Microbiol. PD NOV PY 2007 VL 51 IS 2 BP 372 EP 380 DI 10.1111/j.1574-695X.2007.00313.x PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 218BO UT WOS:000249991200015 PM 17727655 ER PT J AU Lee, JK Edderkaoui, M Truong, P Ohno, I Jang, KT Berti, A Pandol, SJ Gukovskaya, AS AF Lee, Jong Kyun Edderkaoui, Mouad Truong, Patrick Ohno, Izumi Jang, Kee-Taek Berti, Andrea Pandol, Stephen J. Gukovskaya, Anna S. TI NADPH oxidase promotes pancreatic cancer cell survival via inhibiting JAK2 dephosphorylation by tyrosine phosphatases SO GASTROENTEROLOGY LA English DT Article ID EARLY GENE-PRODUCTS; NF-KAPPA-B; REACTIVE OXYGEN; REDOX REGULATION; SIGNAL-TRANSDUCTION; NAD(P)H OXIDASE; P53 STATUS; KINASE; ACTIVATION; APOPTOSIS AB Background & Alms: Growth factors, such as insulin-like growth factor-1 (IGF-I), protect pancreatic cancer (PaCa) cells from death. We recently showed that reactive oxygen species (ROS) produced by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase Nox4 mediate the antiapoptotic effect of growth factors. Here, we examine the mechanisms of the antiapoptotic role of NADPH oxidase. We hypothesized that ROSS produced by NADPH oxidase inhibit key protein tyrosine phosphatases (PTPs) and thus sustain the activation of kinases mediating antiapoptotic pathways in PaCa cells. Methods: Transfections and pharmacologic inhibition were used to assess the effects of NADPH oxidase on Janus kinase 2 (JAK2) kinase, the low molecular weight-protein tyrosine phosphatase (LMW-PTP), and apoptosis. Results: We found that 1 target of ROSS is JAK2, an important antiapoptotic kinase in PaCa cells. Both serum-induced and IGF-I biphasic JAK2 phosphorylation, with a rapid (minutes) and transient first phase, and a slow and sustained (24-72 hours) second phase. Nox4 mediated the sustained phase of JAK2 phosphorylation, which was required for the antiapoptotic effects of IGF-I and serum. Transfection experiments identified the LMW-PTP as a negative regulator of sustained JAK2 phosphorylation. Growth factors inhibited LMW-PTP through its oxidation by NADPH oxidase. LMW-PTP colocalizes with Nox4 both in PaCa cells and in human pancreatic adenocarcinoma. Conclusions: The results suggest a novel signaling pathway, in which NADPH oxidase activation results in inhibition of PTPs, such as LMW-PTP, leading, in turn, to enhanced and sustained phosphorylation of kinases, such as JAK2, and suppression of apoptosis. This pathway mediates the prosurvival effect of ROSs and suggests new targets for pancreatic cancer treatment. C1 Vet Affairs Greater Los Angeles Healthcare Syst, W Los Angeles Healthcare Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Los Angeles, CA USA. Sungkyunkwan Univ, Samsung Med Ctr, Seoul, South Korea. Univ Florence, I-50121 Florence, Italy. RP Gukovskaya, AS (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, W Los Angeles Healthcare Ctr, Bldg 258,Room 340,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM agukovsk@ucla.edu FU NCI NIH HHS [R01-CA119025-01] NR 43 TC 79 Z9 80 U1 0 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD NOV PY 2007 VL 133 IS 5 BP 1637 EP 1648 DI 10.1053/j.gastro.2007.08.022 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 229QV UT WOS:000250820100030 PM 17983808 ER PT J AU Brandt, LJ AF Brandt, Lawrence J. TI Mediastinal cryptococcal abscess diagnosed by EUS-FNA SO GASTROINTESTINAL ENDOSCOPY LA English DT Editorial Material C1 Massachusetts Gen Hosp, Gastroenterol Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Brandt, LJ (reprint author), Massachusetts Gen Hosp, Gastroenterol Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0016-5107 J9 GASTROINTEST ENDOSC JI Gastrointest. Endosc. PD NOV PY 2007 VL 66 IS 5 BP 1023 EP 1024 DI 10.1016/j.gie.2007.06.010 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 231XB UT WOS:000250981400028 ER PT J AU Ponder, CA Kliethermes, CL Drew, MR Muller, J Das, K Risbrough, VB Crabbe, JC Gilliam, TC Palmer, AA AF Ponder, C. A. Kliethermes, C. L. Drew, M. R. Muller, J. Das, K. Risbrough, V. B. Crabbe, J. C. Gilliam, T. Conrad Palmer, A. A. TI Selection for contextual fear conditioning affects anxiety-like behaviors and gene expression SO GENES BRAIN AND BEHAVIOR LA English DT Article DE anxiety; behavioral genetics; contextual fear conditioning; correlated traits; emotionality; gene expression; selective breeding ID OPEN-FIELD ACTIVITY; POTENTIATED STARTLE PARADIGM; TRAIT LOCUS ANALYSIS; MATERNAL-BEHAVIOR; FREEZING BEHAVIOR; LABORATORY MICE; ANIMAL-MODELS; RAT; MOUSE; ETHANOL AB Conditioned fear and anxiety-like behaviors have many similarities at the neuroanatomical and pharmacological levels, but their genetic relationship is less well defined. We used short-term selection for contextual fear conditioning (FC) to produce outbred mouse lines with robust genetic differences in FC. The high and low selected lines showed differences in fear learning that were stable across various training parameters and were not secondary to differences in sensitivity to the unconditioned stimulus (foot shock). They also showed a divergence in fear potentiated startle, indicating that differences induced by selection generalized to another measure of fear learning. However, there were no differences in performance in a Pavlovian approach conditioning task or the Morris water maze, indicating no change in general learning ability. The high fear learning line showed greater anxiety-like behavior in the open field and zero maze, confirming a genetic relationship between FC and anxiety-like behavior. Gene expression analysis of the amygdala and hippocampus identified genes that were differentially expressed between the two lines. Quantitative trait locus (QTL) analysis identified several chromosomal regions that may underlie the behavioral response to selection; cis-acting expression QTL were identified in some of these regions, possibly identifying genes that underlie these behavioral QTL. These studies support the validity of a broad genetic construct that includes both learned fear and anxiety and provides a basis for further studies aimed at gene identification. C1 Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA. Columbia Univ, Dept Genet & Dev, New York, NY USA. Univ Calif San Francisco, Ernest Gallo Clin & Res Ctr, Emeryville, CA USA. Columbia Univ, Ctr Neurobiol & Behav, Dept Psychiat, New York, NY 10032 USA. New York State Psychiat Inst & Hosp, Dept Dev Neurosci, New York, NY USA. Columbia Univ, Gertrude H Sergievsky Ctr, New York, NY USA. Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. Oregon Hlth & Sci Univ, Portland Alcohol Res Ctr, Dept Behav Neurosci, Portland, OR USA. Portland VA Med Ctr, Portland, OR USA. Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA. Univ Chicago, Dept Human Genet & Psychiat, Chicago, IL 60637 USA. RP Ponder, CA (reprint author), Univ Chicago, Dept Human Genet, 920 E 58th St,CLSC 507D, Chicago, IL 60637 USA. EM aap@uchicago.edu RI Palmer, Abraham/L-2158-2014; Drew, Michael/M-4787-2016 OI Palmer, Abraham/0000-0003-3634-0747; Drew, Michael/0000-0002-3883-1542 FU NIAAA NIH HHS [AA10270, AA12714, P60 AA010760]; NIMH NIH HHS [MH70933] NR 61 TC 58 Z9 64 U1 5 U2 12 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1601-1848 J9 GENES BRAIN BEHAV JI Genes Brain Behav. PD NOV PY 2007 VL 6 IS 8 BP 736 EP 749 DI 10.1111/j.1601-183X.2007.00306.x PG 14 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 225XZ UT WOS:000250552900006 PM 17309658 ER PT J AU Furnari, FB Fenton, T Bachoo, RM Mukasa, A Stommel, JM Stegh, A Hahn, WC Ligon, KL Louis, DN Brennan, C Chin, L DePinho, RA Cavenee, WK AF Furnari, Frank B. Fenton, Tim Bachoo, Robert M. Mukasa, Akitake Stommel, Jayne M. Stegh, Alexander Hahn, William C. Ligon, Keith L. Louis, David N. Brennan, Cameron Chin, Lynda DePinho, Ronald A. Cavenee, Webster K. TI Malignant astrocytic glioma: genetics, biology, and paths to treatment SO GENES & DEVELOPMENT LA English DT Review ID EPIDERMAL-GROWTH-FACTOR; COMPARATIVE GENOMIC HYBRIDIZATION; HUMAN-BRAIN-TUMORS; CANCER STEM-CELLS; PHASE-II TRIAL; TYROSINE KINASE INHIBITOR; HUMAN GLIOBLASTOMA CELLS; FOCAL ADHESION KINASE; CONFERS ENHANCED TUMORIGENICITY; FORKHEAD TRANSCRIPTION FACTORS AB Malignant astrocytic gliomas such as glioblastoma are the most common and lethal intracranial tumors. These cancers exhibit a relentless malignant progression characterized by widespread invasion throughout the brain, resistance to traditional and newer targeted therapeutic approaches, destruction of normal brain tissue, and certain death. The recent confluence of advances in stem cell biology, cell signaling, genome and computational science and genetic model systems have revolutionized our understanding of the mechanisms underlying the genetics, biology and clinical behavior of glioblastoma. This progress is fueling new opportunities for understanding the fundamental basis for development of this devastating disease and also novel therapies that, for the first time, portend meaningful clinical responses. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Appl Canc Sci,Belfer Inst Innovat Canc Sci, Boston, MA 02115 USA. Univ Calif San Diego, Ludwig Inst Canc Res, La Jolla, CA 92093 USA. Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. Univ Calif San Diego, Ctr Canc, La Jolla, CA 92093 USA. Univ Texas, SW Med Sch, Dept Neurol, Dallas, TX 75390 USA. Univ Texas, SW Med Sch, Dept Med, Dallas, TX 75390 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, Dept Neurosurg, New York, NY 10065 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Dermatol, Boston, MA 02115 USA. Univ Calif San Diego, Ctr Mol Genet, La Jolla, CA 92093 USA. RP DePinho, RA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Ctr Appl Canc Sci,Belfer Inst Innovat Canc Sci, 44 Binney St, Boston, MA 02115 USA. EM ron_depinho@dfci.harvard.edu; wcavenee@ucsd.edu RI leng, xianwei/F-9073-2011; OI Brennan, Cameron/0000-0003-4064-8891; Fenton, Tim/0000-0002-4737-8233 FU NCI NIH HHS [CA099041, CA95616] NR 306 TC 1039 Z9 1078 U1 30 U2 183 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI COLD SPRING HARBOR PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD NOV 1 PY 2007 VL 21 IS 21 BP 2683 EP 2710 DI 10.1101/gad.1596707 PG 28 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 226WB UT WOS:000250618100003 PM 17974913 ER PT J AU Ogino, S Kawasaki, T Kirkner, GJ Suemoto, Y Meyerhardt, JA Fuchs, CS AF Ogino, Shuji Kawasaki, Takako Kirkner, Gregory J. Suemoto, Yuko Meyerhardt, Jeffrey A. Fuchs, Charles S. TI Molecular correlates with MGMT promoter methylation and silencing support CpG island methylator phenotype-low (CIMP-low) in colorectal cancer SO GUT LA English DT Article ID O-6-METHYLGUANINE DNA METHYLTRANSFERASE; POPULATION-BASED SAMPLE; A-T TRANSITIONS; MICROSATELLITE INSTABILITY; G-C; SERRATED POLYPS; BRAF MUTATION; COLON-CANCER; K-RAS; HYPERMETHYLATION AB Background: The CpG island methylator phenotype (CIMP or CIMP-high) with widespread promoter methylation is a distinct epigenetic phenotype in colorectal cancer. In contrast, a phenotype with less widespread promoter methylation (CIMP-low) has not been well characterised. O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation and silencing have been associated with G. A mutations and microsatellite instability-low (MSI-low). Aim: To examine molecular correlates with MGMT methylation/silencing in colorectal cancer. Methods: Utilising MethyLight technology, we quantified DNA methylation in MGMT and eight other markers (a CIMP-diagnostic panel; CACNA1G, CDKN2A (p16), CRABP1, IGF2, MLH1, NEUROG1, RUNX3 and SOCS1) in 920 population-based colorectal cancers. Results: Tumours with both MGMT methylation and loss were correlated positively with MSI-low (p = 0.02), CIMP-high (>= 6/8 methylated CIMP markers, p = 0.005), CIMP-low (1/8-5/8 methylated CIMP markers, p = 0.002, compared to CIMP-0 with 0/8 methylated markers), KRAS G. A mutation (p = 0.02), and inversely with 18q loss of heterozygosity (p = 0.0002). Tumours were classified into nine MSI/CIMP subtypes. Among the CIMP-low group, tumours with both MGMT methylation and loss were far more frequent in MSI-low tumours (67%, 12/18) than MSI-high tumours (5.6%, 1/18; p = 0.0003) and microsatellite stable (MSS) tumours (33%, 52/160; p = 0.008). However, no such relationship was observed among the CIMP-high or CIMP-0 groups. Conclusion: The relationship between MGMT methylation/silencing and MSI-low is limited to only CIMP-low tumours, supporting the suggestion that CIMP-low in colorectal cancer may be a different molecular phenotype from CIMP-high and CIMP-0. Our data support a molecular difference between MSI-low and MSS in colorectal cancer, and a possible link between CIMP-low, MSI-low, MGMT methylation/loss and KRAS mutation. C1 Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Harvard Univ, Dept Med Oncol, Dana Farber Canc Inst, Sch Med,BWH Pathol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. RP Ogino, S (reprint author), Harvard Univ, Dept Med Oncol, Dana Farber Canc Inst, Sch Med,BWH Pathol, 75 Francis St, Boston, MA 02115 USA. EM shuji_ogino@dfci.harvard.edu FU NCI NIH HHS [P01 CA55075, P01 CA055075, P01 CA087969, P01 CA87969] NR 51 TC 57 Z9 60 U1 1 U2 4 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 J9 GUT JI Gut PD NOV PY 2007 VL 56 IS 11 BP 1564 EP 1571 DI 10.1136/gut.2007.119750 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 220QB UT WOS:000250170500018 PM 17339237 ER PT J AU Nagymanyoki, Z Callahan, MJ Parast, MM Fulop, V Mok, SC Berkowitz, RS AF Nagymanyoki, Zoltan Callahan, Michael J. Parast, Mana M. Fulop, Vilmos Mok, Samuel C. Berkowitz, Ross S. TI Immune cell profiling in normal pregnancy, partial and complete molar pregnancy SO GYNECOLOGIC ONCOLOGY LA English DT Article DE gestational trophoblastic disease; T lymphocytes; natural killer cells; regulatory T lymphocytes ID NATURAL-KILLER-CELLS; REGULATORY T-CELLS; LYMPHOCYTE-PROLIFERATION INVITRO; FETAL-MATERNAL INTERFACE; HYDATIDIFORM MOLE; GRANZYME-B; NK CELLS; ACTIVATION; EFFECTOR; MACROMOLECULES AB Objectives. Cytotoxic T cells (Tc) and natural killer (NK) cells may play a role in controlling trophoblast invasion. This study was undertaken to determine the level of infiltration and antigen profile of immune cells and explore their relationship in normal placenta (NP) and molar tissues to better understand the biology of gestational trophoblastic diseases. Materials and methods. Immunolocalization of CD8, Granzyme B (GrB), and FoxP3 was performed on sections prepared from II gestational age-matched NP, 19 partial moles (PM), and 18 complete moles (CM) to characterize effector (GrB+CD8+) and GrB- (GrB-CD8+) Tc cells, GrB+ NK cells (GrB+CD8-), and Treg (FoxP3+) cells. Results. Immune cells infiltrated into the implantation site of normal placenta, PM, and CM with increasing frequency. Effector and GrBTc, GrB+ NK and Treg infiltration in the CM were significantly stronger than seen in the normal placenta (p=0.002, p=0.007, p=0.002, respectively). Immune cell infiltration was not detected in the villi or trophoblast of gestational tissues. Treg infiltration in the implantation site was only observed in PM and CM. In CM and PM Tc infiltration positively correlated with Treg infiltration (p=0.035), but Treg infiltration did not correlate with the Tc effector ratio (effector Tc cells/all Tc cells). Conclusion. In CM the cellular immune response in the implantation site was significantly more vigorous than seen in normal placenta. These observations demonstrate that in the implantation site of CM, the number of effector Tc and GrB+ NK cells are increased and Treg cells may negatively regulate T lymphocyte activation. (c) 2007 Elsevier Inc. All rights reserved. C1 Harvard Univ, Sch Med,Dept Obstet & Gynecol, Dana Farber Canc Inst,Lab Gynecol Oncol, Brigham & Womens Hosp,New England Trophoblast Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Pathol,Div Womens & Perinatal Pathol, Boston, MA 02115 USA. Natl Hlth Ctr, Dept Obstet & Gynecol, Budapest, Hungary. Semmelweis Univ, H-1085 Budapest, Hungary. RP Berkowitz, RS (reprint author), Harvard Univ, Sch Med,Dept Obstet & Gynecol, Dana Farber Canc Inst,Lab Gynecol Oncol, Brigham & Womens Hosp,New England Trophoblast Dis, 44 Binney St, Boston, MA 02115 USA. EM rberkowitz@partners.org NR 42 TC 9 Z9 9 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD NOV PY 2007 VL 107 IS 2 BP 292 EP 297 DI 10.1016/j.ygyno.2007.06.028 PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 227KF UT WOS:000250654900025 PM 17878059 ER PT J AU Horowitz, NS Hua, J Powell, MA Gibb, RK Mutch, DG Herzog, TJ AF Horowitz, Neil S. Hua, Jun Powell, Matthew A. Gibb, Randall K. Mutch, David G. Herzog, Thomas J. TI Novel cytotoxic agents from an unexpected source: Bile acids and ovarian tumor apoptosis SO GYNECOLOGIC ONCOLOGY LA English DT Article DE bile salts; ovarian cancer; MTT assay ID URSODEOXYCHOLIC ACID; COLON-CANCER; CHENODEOXYCHOLIC ACID; DEOXYCHOLIC-ACID; STAGE-III; CELLS; DERIVATIVES; PROLIFERATION; PACLITAXEL; RESISTANCE AB Objective. Unique biologic activities have been identified for the 4 different bile acids: cholic acid (CA, chenodeoxycholic acid (CDCA), deoxycholic acid (DCA), and ursodeoxycholic acid (UDCA). The aim of this study was to examine and compare the effects of these 4 bile acids on the human ovarian cancer cell lines A2780 and A2780-CP-R(cisplatin-resistant) and to evaluate mechanisms of action. Methods. Antiproliferative effects were determined by the cytotoxic MTT assay. Cells undergoing apoptosis were identified by morphologic analysis of cells stained using Diff-Quick and nuclear staining with DAPI and by quantitative nucleosome ELISA assay. Cells were lysed in buffer after 24 h of exposure to three different concentrations of bile acid (50 mM, 200 mM, and 400 mM) and protein concentrations were determined. Cell extracts containing 25 mg of protein were assayed for protein kinase C (PKC) enzyme activity. Results. None of the bile acids stimulated proliferation of ovarian cancer cells. CA and UDCA had only minimal cytotoxic effect even at maximum concentrations. In contrast, DCA and CDCA administration resulted in statistically significant dose-dependent cytotoxicity in both platinum sensitive and platinum-resistant cell lines (p < 0.05). Cells incubated with DCA and CDCA exhibited morphologic features characteristic of apoptosis. The quantitative nucleosome ELISA assay demonstrated over 10 times increased nucleosome levels after cells were treated for 24 h by DCA and CDCA at 200 mM and 400 mM as compared to CA or UDCA treatment and to untreated controls (p < 0.01). All 4 bile acids reduced PKC activity at concentrations of 200 and 400 mM (p < 0.01). Conclusions. CDCA and DCA have significant cytotoxic activity in ovarian cancer cells via induction of apoptosis. The mechanism of apoptosis appears to be mediated by alternative kinases distinct from PKC. CDCA and DCA may have clinical utility in the treatment of ovarian cancer pending in vivo confirmation of activity especially in cisplatin-resistant disease. (c) 2007 Elsevier Inc. All rights reserved. C1 Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Washington Univ, Sch Med, St Louis, MO USA. RP Herzog, TJ (reprint author), Columbia Univ Coll Phys & Surg, 161 Ft Washington,Ave 8th, New York, NY 10032 USA. EM th2l35@columbia.edu NR 21 TC 11 Z9 12 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD NOV PY 2007 VL 107 IS 2 BP 344 EP 349 DI 10.1016/j.ygyno.2007.07.072 PG 6 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 227KF UT WOS:000250654900033 PM 17720233 ER PT J AU Ng, AK Birdwell, RL Diller, LR Neuberg, D Garber, JE Fisher, DC Stevenson, MA Mauch, PM AF Ng, A. K. Birdwell, R. L. Diller, L. R. Neuberg, D. Garber, J. E. Fisher, D. C. Stevenson, M. A. Mauch, P. M. TI Breast magnetic resonance imaging (MRI) screening in female survivors of hodgkin lymphoma (HL): Preliminary findings SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 7th International Symposium on Hodgkin Lymphoma CY NOV 03-07, 2007 CL Cologne, GERMANY C1 [Ng, A. K.; Birdwell, R. L.; Diller, L. R.; Neuberg, D.; Garber, J. E.; Fisher, D. C.; Stevenson, M. A.; Mauch, P. M.] Brigham & Womens Hosp, Harvard Med Sch, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD NOV PY 2007 VL 92 SU 5 BP 2 EP 2 PG 1 WC Hematology SC Hematology GA 224UA UT WOS:000250470800006 ER PT J AU Rahemtullah, A Reichard, KK Dorn, ME Preffer, FI Harris, NL Hasserjian, RP AF Rahemtullah, A. Reichard, K. K. Dorn, M. E. Preffer, F. I. Harris, N. L. Hasserjian, R. P. TI Double-positive CD4+CD8+ T-cell populations in nodular lymphocyte predominant Hodgkin lymphoma: Further characterization and relationship to other entities SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 7th International Symposium on Hodgkin Lymphoma CY NOV 03-07, 2007 CL Cologne, GERMANY C1 [Rahemtullah, A.; Dorn, M. E.; Preffer, F. I.; Harris, N. L.; Hasserjian, R. P.] Massachusetts Gen Hosp, Harvard Med Sch, Dept Pathol, Boston, MA 02114 USA. Univ New Mexico, Albuquerque, NM 87131 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD NOV PY 2007 VL 92 SU 5 BP 2 EP 3 PG 2 WC Hematology SC Hematology GA 224UA UT WOS:000250470800008 ER PT J AU Juszczynski, P Ouyang, J Monti, S Rodig, S Takeyama, K Abramson, J Chen, W Kutok, JL Rabinovich, GA Shipp, MA AF Juszczynski, P. Ouyang, J. Monti, S. Rodig, S. Takeyama, K. Abramson, J. Chen, W. Kutok, J. L. Rabinovich, G. A. Shipp, M. A. TI Galectin 1 mediates tumor escape in HL SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Meeting Abstract CT 7th International Symposium on Hodgkin Lymphoma CY NOV 03-07, 2007 CL Cologne, GERMANY C1 [Juszczynski, P.; Ouyang, J.; Takeyama, K.; Abramson, J.; Chen, W.; Shipp, M. A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA USA. [Monti, S.] Broad Inst, Cambridge, MA USA. [Rodig, S.; Kutok, J. L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA USA. [Rabinovich, G. A.] Univ Buenos Aires, CONICET, Fac Exact & Nat Sci, IBYME,Inst Biol & Expt Med, Buenos Aires, DF, Argentina. NR 1 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD NOV PY 2007 VL 92 SU 5 BP 10 EP 10 PG 1 WC Hematology SC Hematology GA 224UA UT WOS:000250470800027 ER PT J AU Ring, D AF Ring, David TI Apparent capitellar fractures SO HAND CLINICS LA English DT Article ID TOTAL ELBOW ARTHROPLASTY; DISTAL HUMERAL FRACTURES; INTERNAL-FIXATION; CAPITULUM HUMERI; ELDERLY-PATIENTS; OPEN REDUCTION; ULNAR NERVE; REPLACEMENT; MANAGEMENT; OSTEOTOMY AB Isolated capitellar fractures are rare but are identified as such, even when they are more complex, because the displaced capitellar fracture is usually the most obvious and identifiable radiographic finding and because teaching has traditionally underempha-sized the involvement of the trochlea in such fractures. The author prefers the term,apparent capitellar fractures' and draws on his experience to explain why lie favors three-dimensional CT for depicting fracture detail. This article discusses treatment options, emphasizing open reduction and internal fixation to restore the native elbow. Operative techniques, including extensile lateral exposure and olecranon osteotomy; fixation techniques; and elbow arthroplasty, are described. Complications, such as ulnar neuropathy and infection, are also covered. C1 Massachusetts Gen Hosp, Dept Orthoped Surg, Orthopaed Trauma Serv, Hand & Upper Extrem Serv, Boston, MA 02114 USA. RP Ring, D (reprint author), Massachusetts Gen Hosp, Dept Orthoped Surg, Orthopaed Trauma Serv, Hand & Upper Extrem Serv, Yawkey 2100,55 Fruit St, Boston, MA 02114 USA. EM dring@partners.org NR 32 TC 2 Z9 3 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0749-0712 J9 HAND CLIN JI Hand Clin. PD NOV PY 2007 VL 23 IS 4 BP 471 EP + DI 10.1016/j.hcl.2007.09.004 PG 10 WC Orthopedics SC Orthopedics GA 248QB UT WOS:000252168200009 PM 18054674 ER PT J AU Wittmann, C Moore, C Van Niel, MS Noam, G AF Wittmann, Christine Moore, Cynthia Van Niel, Maureen Sayres Noam, Gil TI Prolonged mourning in a fifteen-year-old girl SO HARVARD REVIEW OF PSYCHIATRY LA English DT Article ID BEREAVED CHILDREN; EXPERIENCE; PARENT; GRIEF; DEATH C1 [Wittmann, Christine; Moore, Cynthia; Noam, Gil] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Wittmann, Christine; Moore, Cynthia] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Noam, Gil] Harvard Univ, Grad Sch Educ, Cambridge, MA 02138 USA. RP Wittmann, C (reprint author), Yawkey 6A,55 Fruit St, Boston, MA 02114 USA. EM cewittmann@partners.org NR 30 TC 0 Z9 0 U1 0 U2 0 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 2007 VL 15 IS 6 BP 301 EP 311 DI 10.1080/10673220701811647 PG 11 WC Psychiatry SC Psychiatry GA 247YI UT WOS:000252118100005 PM 18097840 ER PT J AU Ferris, TG Vogeli, C Marder, J Sennett, CS Campbell, EG AF Ferris, Timothy G. Vogeli, Christine Marder, Jessica Sennett, Cary S. Campbell, Eric G. TI Physician Specialty societies and the development of physician performance measures SO HEALTH AFFAIRS LA English DT Article ID CLINICAL-PERFORMANCE; QUALITY AB Efforts to increase accountability in the delivery of care include attempts to measure performance of individual doctors. Although physician specialty societies may be best positioned to define best practices, they have not yet played a major role in the development of measures. We examined specialty society involvement in measure development through interviews and review of Web sites. We found that a minority (35 percent) of societies were engaged in developing performance measures. Key barriers included member reluctance, lack of resources for development, and problems with data collection; facilitators included strong leadership and the perception of increasing pressure for accountability. C1 Mass Gen Phys Org, Boston, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Amer Board Internal Med, Philadelphia, PA USA. RP Ferris, TG (reprint author), Mass Gen Phys Org, Boston, MA USA. EM tferris@partners.org NR 13 TC 12 Z9 12 U1 1 U2 1 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD NOV-DEC PY 2007 VL 26 IS 6 BP 1712 EP 1719 DI 10.1377/hlthaff.26.6.1712 PG 8 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 234FO UT WOS:000251146300031 PM 17978390 ER PT J AU Richman, LS Bennett, GG Pek, J Siegler, I Williams, RB AF Richman, Laura Smart Bennett, Gary G. Pek, Jolynn Siegler, Ilene Williams, Redford B., Jr. TI Discrimination, dispositions, and cardiovascular responses to stress SO HEALTH PSYCHOLOGY LA English DT Article DE perceived discrimination; hostility; optimism; cardiovascular outcomes ID BLOOD-PRESSURE; CAROTID ATHEROSCLEROSIS; POSITIVE EMOTIONS; UNFAIR TREATMENT; HOSTILITY; HEALTH; REACTIVITY; RECOVERY; WOMEN; MEN AB Objective: Recent research suggests that past exposure to discrimination may influence perceptions of, and physiological responses to, new challenges. The authors examined how race and trait levels of hostility and optimism interact with past exposure to discrimination to predict physiological reactivity and recovery during an anger recall task. Design: A community sample of 165 normotensive Black and White adults participated in an anger recall task while having their cardiovascular function monitored. Main Outcome Measures: Blood pressure and heart rate indicators of physiological reactivity and recovery. Results and Conclusion: Participants had higher reactivity and slower recovery to the anger recall task when they had high past discrimination, low cynicism, or high optimism. The pattern of effects was similar for both racial groups, but Blacks had more acute reactivity and slower recovery than Whites. These results are consistent with the perspective of discrimination as a chronic stressor that is related to acute stress responses, particularly for Blacks. C1 Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. Natl Univ Singapore, Dept Psychol, Singapore 117548, Singapore. Duke Univ, Behav Med Res Ctr, Durham, NC 27706 USA. Duke Univ, Dept Psychol & Neurosci, Durham, NC 27708 USA. RP Richman, LS (reprint author), Duke Univ, Dept Psychol & Neurosci, Box 90085,Flower Dr, Durham, NC 27708 USA. EM lrichman@duke.edu FU NHLBI NIH HHS [P01 HL 36587]; NIMH NIH HHS [1K01 MH 074942-01] NR 46 TC 41 Z9 41 U1 3 U2 10 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0278-6133 J9 HEALTH PSYCHOL JI Health Psychol. PD NOV PY 2007 VL 26 IS 6 BP 675 EP 683 DI 10.1037/0278-6133.26.6.675 PG 9 WC Psychology, Clinical; Psychology SC Psychology GA 230FN UT WOS:000250861700004 PM 18020838 ER PT J AU Seneviratne, SK Bamberg, F Hoffmann, U AF Seneviratne, Sujith K. Bamberg, Fabian Hoffmann, Udo TI CT angiography: front line for acute coronary syndromes now? SO HEART LA English DT Editorial Material ID CHEST-PAIN; COMPUTED-TOMOGRAPHY C1 Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Hoffmann, U (reprint author), Massachusetts Gen Hosp, Cardiac MR PET CT Program, 165 Charles River Plaza Suite 400, Boston, MA 02114 USA. EM uhoffmann@partners.org NR 9 TC 3 Z9 3 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1355-6037 J9 HEART JI Heart PD NOV PY 2007 VL 93 IS 11 BP 1325 EP 1326 DI 10.1136/hrt.2007.122689 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 220HP UT WOS:000250148100003 PM 17933984 ER PT J AU Rahman, S Lundkvist, A Xu, C Sumathipala, R Fujisawa, T Wijelath, E Patel, Y Kanaganayagum, G Sobel, M Gerhardt, H AF Rahman, S. Lundkvist, A. Xu, C. Sumathipala, R. Fujisawa, T. Wijelath, E. Patel, Y. Kanaganayagum, G. Sobel, M. Gerhardt, H. TI ADAM 15 is essential for regulated angiogenesis and VEGF signalling to Akt through proteolytic processing of the urokinase-type plasminogen activator receptor (uPAR) SO HEART LA English DT Meeting Abstract CT Spring Meeting of the British-Society-for-Cardiovascular-Research CY MAR 29-30, 2007 CL Univ Reading, Reading, ENGLAND SP British Soc Cardiovasc Res HO Univ Reading C1 Kings Coll London, Sch Med, Div Cardiovasc Med, Lab Thrombos & Vasc Remodel, London, England. Canc Res UK, Lab Vasc Biol, London, England. Univ Washington, Sch Med, Dept Surg, Vet Affairs Puget Sound Hlth Care Syst,Div Vasc S, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1355-6037 J9 HEART JI Heart PD NOV PY 2007 VL 93 IS 11 MA 003 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 220HP UT WOS:000250148100040 ER PT J AU Li, A Xie, Z Dong, Y Mckay, KM Mckee, ML Tanzi, RE AF Li, Airong Xie, Zhongcong Dong, Yuanlin Mckay, Kenneth M. Mckee, Mary L. Tanzi, Rudolph E. TI Isolation and characterization of the Drosophila ubiquilin ortholog dUbqln: in vivo interaction with early-onset Alzheimer disease genes SO HUMAN MOLECULAR GENETICS LA English DT Article ID AMYLOID PRECURSOR PROTEIN; GROWTH-FACTOR RECEPTOR; EGF RECEPTOR; PARKINSONS-DISEASE; BRAIN DEGENERATION; NOTCH RECEPTOR; CELL-DEATH; NEURODEGENERATION; POLYGLUTAMINE; IDENTIFICATION AB UBQLN1 variants have been associated with increased risk for late-onset Alzheimer's disease (AD). We produced transgenic Drosophila models that either silence (by RNAi) or overexpress the Drosophila ortholog of human UBQLN1, dUbqln. Silencing of dUbqln in the central nervous system led to age-dependent neurodegeneration and shortened lifespan. Silencing of dUbqln in the wing led to wing vein loss that could be partially rescued by mutant rhomboid (rho), a known component of epidermal growth factor receptor signaling pathway. Conversely, overexpression of dUbqln promoted ecotopic wing veins. Overexpression of dUbqln in the eye rescued a small, rough eye phenotype induced by overexpression of Drosophila presenilin (dPsn), and also rescuing dPsn-induced malformations in bristles. In contrast, RNAi silencing of dUbqln enhanced the retinal degenerative defect induced by overexpression of dPsn. Finally, co-overexpression of dUbqln and the human amyloid precursor protein (APP) in the eye significantly reduced the levels of full-length APP and its C-terminal fragment. Collectively, these data support in vivo functional interaction between UBQLN1 and the AD-associated genes, presenilin and APP, and provide further clues regarding the potential role of UBQLN1 in AD pathogenesis. C1 MGH E MIND, Genet & Aging Res Unit, Dept Neurol, Charlestown, MA 02128 USA. Harvard Univ, Sch Med, Charlestown, MA USA. Massachusetts Gen Hosp, Dept Anesthesiol & Crit Care, Charlestown, MA USA. Massachusetts Gen Hosp, Program Membrane Biol, Charlestown, MA USA. RP Tanzi, RE (reprint author), MGH E MIND, Genet & Aging Res Unit, Dept Neurol, 114 16th St, Charlestown, MA 02128 USA. EM tanzi@helix.mgh.harvard.edu FU NIA NIH HHS [P60 AG008812, R01AG014713, K12AG000294]; NIMH NIH HHS [R01MH 60009]; NINDS NIH HHS [K08 NS048140] NR 79 TC 27 Z9 27 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD NOV PY 2007 VL 16 IS 21 BP 2626 EP 2639 DI 10.1093/hmg/ddm219 PG 14 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 227SV UT WOS:000250679000010 PM 17704509 ER PT J AU Lee, DS Massaro, JM Wang, TJ Kannel, WB Benjamin, EJ Kenchaiah, S Levy, D D'Agostino, RB Vasan, RS AF Lee, Douglas S. Massaro, Joseph M. Wang, Thomas J. Kannel, William B. Benjamin, Emelia J. Kenchaiah, Satish Levy, Daniel D'Agostino, Ralph B., Sr. Vasan, Ramachandran S. TI Antecedent blood pressure, body mass index, and the risk of incident heart failure in later life SO HYPERTENSION LA English DT Article DE hypertension; blood pressure; obesity; body mass index; congestive heart failure; cohort studies ID LEFT-VENTRICULAR MASS; PULSE PRESSURE; CARDIOVASCULAR-DISEASE; PRIMARY-CARE; FRAMINGHAM; HYPERTENSION; PREDICTORS; GUIDELINES; OBESITY; STROKE AB Higher blood pressure and body mass index (BMI) are risk factors for heart failure. It is unknown whether the presence of these risk factors in midadulthood affect the future development of heart failure. In the community-based Framingham Heart Study, we examined the associations of antecedent blood pressure and BMI with heart failure incidence in later life. We studied 3362 participants (57% women; mean age: 62 years) who attended routine examinations between 1969 and 1994 and examined their systolic and diastolic blood pressure, pulse pressure, and BMI at current (baseline), recent (average of readings obtained 1 to 10 years before baseline), and remote (average of readings obtained 11 to 20 years before baseline) time periods. During 67 240 person-years of follow-up, 518 participants (280 women) developed heart failure. Current, recent, and remote systolic pressure; pulse pressure; and BMI were individually associated with incident heart failure (all P < 0.001). Recent systolic pressure (hazards ratio [HR] per 1-SD increment: 1.31; 95% CI: 1.11 to 1.55), pulse pressure (HR per 1-SD increment: 1.33; 95% CI: 1.14 to 1.54), and BMI (HR per unit increase: 1.15; 95% CI: 1.08 to 1.23) were associated with heart failure risk even after adjusting for current measures. Similarly, remote systolic pressure (HR per 1 SD: 1.17; 95% CI: 1.04 to 1.31), pulse pressure (HR per 1 SD: 1.17; 95% CI: 1.06 to 1.31), and BMI (HR per unit: 1.09; 95% CI: 1.05 to 1.14) remained associated with incident heart failure after adjusting for current measurements. Higher blood pressure and BMI in midlife are harbingers of increased risk of heart failure in later life. Early risk factor modification may decrease heart failure burden. C1 NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. Univ Toronto, Clin Evaluat Sci & Univ Hlth Network, Toronto, ON, Canada. Boston Univ, Dept Math, Boston, MA 02215 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol, Boston, MA USA. Univ Calif Irvine, Med Ctr, Div Cardiol, Orange, CA USA. NHLBI, Bethesda, MD 20892 USA. Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02215 USA. Boston Univ, Sch Med, Dept Epidemiol & Prevent Med, Boston, MA 02215 USA. Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. RP Vasan, RS (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM vasan@bu.edu RI Lee, Douglas/J-4315-2014; Kenchaiah, Satish/A-1519-2016; OI Benjamin, Emelia/0000-0003-4076-2336; Massaro, Joseph/0000-0002-2682-4812; Ramachandran, Vasan/0000-0001-7357-5970 FU NHLBI NIH HHS [2K24HL04334, K23HL074077]; NIA NIH HHS [AG028321]; PHS HHS [N01-25195] NR 29 TC 44 Z9 48 U1 1 U2 4 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 2007 VL 50 IS 5 BP 869 EP 876 DI 10.1161/HYPERTENSIONAHA.107.095380 PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 225LA UT WOS:000250518200012 PM 17893376 ER PT J AU Ozcan, A Cubukcu, E Bilenca, A Bouma, BE Capasso, F Tearney, GJ AF Ozcan, Aydogan Cubukcu, Ertugrul Bilenca, Alberto Bouma, Brett E. Capasso, Federico Tearney, Guillermo J. TI Differential near-field scanning optical microscopy using sensor arrays SO IEEE JOURNAL OF SELECTED TOPICS IN QUANTUM ELECTRONICS LA English DT Article DE differential NSOM (DNSOM); near-field imaging; near-field scanning optical microscopy (NSOM); SNOM ID COHERENCE TOMOGRAPHY; DIFFRACTION-LIMIT; SINGLE MOLECULES; RESOLUTION; LIGHT; APERTURES; BREAKING; CELLS; PROBE; FILMS AB In this paper, we introduce a new aperture-type near-field scanning optical microscopy (NSOM) imaging concept that relies on specially designed large-area (e.g., >200 nm x 200 nm) aperture geometries having sharp corners. Unlike in conventional NSOM, the spatial resolution of this near-field imaging modality is not determined by the size of the aperture, but rather by the sharpness of the corners of the large aperture. This approach significantly improves the light throughput of the near-field probe and, hence, increases the SNR. Here, we discuss the basic concepts of this near-field microscopy approach and illustrate both theoretically and experimentally how an array of detectors can be utilized to further improve the SNR of the near-field image. The results of this work are particularly relevant for imaging of biological samples at a spatial resolution of <50 nm with significantly improved image quality. C1 [Ozcan, Aydogan] Univ Calif Los Angeles, Dept Elect Engn, Los Angeles, CA 90095 USA. [Ozcan, Aydogan] Univ Calif Los Angeles, Biomed Engn IDP, Los Angeles, CA 90095 USA. [Cubukcu, Ertugrul; Capasso, Federico] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA. [Bilenca, Alberto; Bouma, Brett E.; Tearney, Guillermo J.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Bouma, Brett E.] Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Tearney, Guillermo J.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Ozcan, A (reprint author), Univ Calif Los Angeles, Dept Elect Engn, Los Angeles, CA 90095 USA. EM ozcan@ucla.edu RI Cubukcu, Ertugrul/F-4807-2010; Cubukcu, Ertugrul/D-5007-2012; Ozcan, Aydogan/I-2608-2013 OI Ozcan, Aydogan/0000-0002-0717-683X NR 46 TC 7 Z9 7 U1 2 U2 7 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 1077-260X J9 IEEE J SEL TOP QUANT JI IEEE J. Sel. Top. Quantum Electron. PD NOV-DEC PY 2007 VL 13 IS 6 BP 1721 EP 1729 DI 10.1109/JSTQE.2007.910799 PG 9 WC Engineering, Electrical & Electronic; Optics; Physics, Applied SC Engineering; Optics; Physics GA 249UP UT WOS:000252255800018 ER PT J AU Wuerffe, R Wang, L Grigera, F Manis, J Selsing, E Perlot, T Alt, FW Cogne, M Pinaud, E Kenter, AL AF Wuerffe, Robert Wang, Lili Grigera, Fernando Manis, John Selsing, Erik Perlot, Thomas Alt, Frederick W. Cogne, Michel Pinaud, Eric Kenter, Amy L. TI S-S Synapsis during class switch recombination is promoted by distantly located transcriptional elements and activation-induced deaminase SO IMMUNITY LA English DT Article ID DOUBLE-STRAND BREAKS; IN-VIVO; IGH LOCUS; B-CELLS; SOMATIC HYPERMUTATION; REGION RECOMBINATION; DNA-DAMAGE; AID; SITES; MU AB Molecular mechanisms underlying synapsis of activation-induced deaminase (AID)-targeted S regions during class switch recombination (CSR) are poorly understood. By using chromosome conformation capture techniques, we found that in B cells, the E mu and 3'E alpha enhancers were in close spatial proximity, forming a unique chromosomal loop configuration. B cell activa tion led to recruitment of the germline transcript (GLT) promoters to the E mu:3'E alpha complex in a cytokine-dependent fashion. This structure facilitated S-S synapsis because S mu was proximal to Et and a downstream S region was corecruited with the targeted GLT promoter to E mu:3'E alpha. We propose that GILT promoter association with the E mu:3'E alpha complex creates an architectural scaffolding that promotes S-S synapsis during CSR and that these interactions are stabilized by AID. Thus, the S-S synaptosome is formed as a result of the self-organizing transcription system that regulates GILT expression and may serve to guard against spurious chromosomal translocations. C1 Univ Illinois, Coll Med, Dept Microbiol & Immunol, Chicago, IL 60612 USA. Harvard Med Sch, Childrens Hosp, Dept Pathol, Joint Program Transfusion Med, Boston, MA 02115 USA. Tufts Univ, Sch Med, Dept Pathol, Program Immunol, Boston, MA 02111 USA. Harvard Med Sch, Childrens Hosp, Howard Hughes Med Inst, Immune Dis Inst,Dept Genet, Boston, MA 02115 USA. Univ Vienna, A-1010 Vienna, Austria. Univ Limoges, Immunol Lab, F-87025 Limoges, France. RP Kenter, AL (reprint author), Univ Illinois, Coll Med, Dept Microbiol & Immunol, Chicago, IL 60612 USA. EM star1@uic.edu RI PINAUD, Eric/O-8443-2016; cogne, michel/D-7370-2015 OI PINAUD, Eric/0000-0001-7405-9273; cogne, michel/0000-0002-8519-4427 FU NCI NIH HHS [P01CA092615]; NIAID NIH HHS [R01 AI052400, AI052400, AI24465, R01 AI024465, R01 AI052400-05A2] NR 44 TC 100 Z9 100 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD NOV PY 2007 VL 27 IS 5 BP 711 EP 722 DI 10.1016/j.immuni.2007.09.007 PG 12 WC Immunology SC Immunology GA 235YA UT WOS:000251269000006 PM 17980632 ER PT J AU Naito, T Arco, PGD Williams, CJ Georgopoulos, K AF Naito, Taku Arco, Pablo Gomez-Del Williams, Christine J. Georgopoulos, Katia TI Antagonistic interactions between lkaros and the chromatin remodeler Mi-2 beta determine silencer activity and Cd4 gene expression SO IMMUNITY LA English DT Article ID T-LYMPHOCYTE DEVELOPMENT; DNA-BINDING PROTEINS; HISTONE DEACETYLASE; TRANSCRIPTIONAL REPRESSION; RUNX PROTEINS; CELL DIFFERENTIATION; IKAROS FAMILY; NURD COMPLEX; N-COR; THYMOCYTES AB Lineage commitment is induced by changes in gene expression dictated by the intimate interaction between transcription factors and chromatin regulators. Here, we revealed the antagonistic interplay between Ilkaros and its associate the chromatin remodeler Mi-2 beta during T cell development, as exemplified by the regulation of Cd4 expression. Loss of lkaros or Mi-2 beta led to activation or repression, respectively, of the Cd4 locus at inappropriate stages of development. Their combined mutation reverted to normal CD4 expression. In double-negative thymocytes, lkaros binding to the Cd4 silencer contributed to its repressive activity. In double-positive thymocytes, concomitant binding of Mi-2 beta with lkaros to the Cd4 silencer caused silencer inactivation, thereby allowing for CD4 expression. Mi-2 beta facilitated recruitment of histone acetyl transferases to the silencer. This recruitment possibly antagonized Ikaros and associated repressive activities. Thus, concomitant interactions between functionally opposing chromatin-regulating machineries are an important mode of gene regulation during lineage determination. C1 Univ Autonoma Madrid, Cardiovasc Res Ctr, E-28029 Madrid, Spain. Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. RP Georgopoulos, K (reprint author), Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA. EM katia.georgopoulos@cbrc2.mgh.harvard.edu RI Gomez-del Arco, Pablo/L-2728-2013 OI Gomez-del Arco, Pablo/0000-0001-6748-7157 FU NIAID NIH HHS [AI380342] NR 46 TC 54 Z9 56 U1 1 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD NOV PY 2007 VL 27 IS 5 BP 723 EP 734 DI 10.1016/j.immuni.2007.09.008 PG 12 WC Immunology SC Immunology GA 235YA UT WOS:000251269000007 PM 17980631 ER PT J AU Hill, JA Feuerer, M Tash, K Haxhinasto, S Perez, J Melamed, R Mathis, D Benoist, C AF Hill, Jonathan A. Feuerer, Markus Tash, Kaley Haxhinasto, Sokol Perez, Jasmine Melamed, Rachel Mathis, Diane Benoist, Christophe TI Foxp3 transcription-factor-dependent and -independent regulation of the regulatory T cell transcriptional signature SO IMMUNITY LA English DT Article ID LINEAGE DIVERSIFICATION; POSITIVE SELECTION; IMMUNE-RESPONSES; B-LYMPHOPOIESIS; DOWN-REGULATION; SELF-TOLERANCE; CUTTING EDGE; TARGET GENES; INDUCTION; DIFFERENTIATION AB The CD4(+)CD25(+) lineage of regulatory T (Treg) cells plays a key role in controlling immune and autoimmune responses and is characterized by a unique transcriptional signature. The transcription factor Foxp3 had been thought to determine the Treg cell lineage, a hypothesis challenged by recent observations. We have performed a cross-sectional analysis of the Treg cell signature in Treg-like cells generated under a number of conditions, with or without Foxp3, to delineate the elements that can be ascribed to T cell activation, interleukin-2, transforming growth factor-beta (TGF-beta) signaling, or Foxp3 itself. These influences synergized to determine many of the signature's components. Much of the Treg cell signature was not ascribable to Foxp3 because it contained gene clusters that are coregulated with, but not transactivated by, Foxp3. Thus, a higher level of regulation upstream of Foxp3 determines the lineage, distinct from elements downstream of Foxp3 that are essential for its regulatory properties. C1 Brigham & Womens Hosp, Harvard Med Sch, Joslin Diabet Ctr, Dept Med,Sect Immunol & Immunogenet, Boston, MA 02215 USA. RP Benoist, C (reprint author), Brigham & Womens Hosp, Harvard Med Sch, Joslin Diabet Ctr, Dept Med,Sect Immunol & Immunogenet, Boston, MA 02215 USA. EM cbdm@joslin.harvard.edu OI Melamed, Rachel/0000-0003-3089-9806 FU NIAID NIH HHS [1R01AI51530-5] NR 51 TC 303 Z9 309 U1 3 U2 13 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD NOV PY 2007 VL 27 IS 5 BP 786 EP 800 DI 10.1016/j.immuni.2007.09.010 PG 15 WC Immunology SC Immunology GA 235YA UT WOS:000251269000012 PM 18024188 ER PT J AU Lipsky, BA Weigelt, JA Gupta, V Killian, A Peng, MM AF Lipsky, Benjamin A. Weigelt, John A. Gupta, Vikas Killian, Aaron Peng, Michael M. TI Skin, soft tissue, bone, and joint infections in hospitalized patients: Epidemiology and microbiological, clinical, and economic outcomes SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID RESISTANT STAPHYLOCOCCUS-AUREUS; ANTIMICROBIAL SUSCEPTIBILITY PATTERNS; PROGRAM UNITED-STATES; LARGE US DATABASE; METHICILLIN-RESISTANT; FOOT INFECTIONS; MANAGEMENT; SURVEILLANCE; PNEUMONIA; DIAGNOSIS AB BACKGROUND. Infections involving skin, soft tissue, bone, or joint (SSTBJ) are common and often require hospitalization. There are currently few published studies on the epidemiology and clinical and economic outcomes of these infections, whether acquired in the community or healthcare setting, in a large population. OBJECTIVE. To characterize outcomes of culture-proven SSTBJ infection in hospitalized patients, using information from a large database. DESIGN. We identified patients hospitalized in 134 institutions during 2002-2003 for whom specific International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes and a culture-positive SSTBJ specimen were recorded. Patients were classified into 4 clinical groups based on the type and clinical severity of infection. Patients in each group were further classified on the basis of whether their infection was community acquired or healthcare associated and whether it was complicated or uncomplicated. RESULTS. We identified 12,506 patients with culture-positive infections and categorized them as having cellulitis (37.3%), osteomyelitis or septic arthritis (22.4%), surgical wound infection (26.1%), device-associated or prosthesis infection (7.2%), or other SSTBJ infection (6.9%). Monomicrobial infection was reported for 59% of patients, 54.6% of whom had Staphylococcus aureus as the etiologic agent. Of all S. aureus isolates recovered, 1,121 (28.0%) of 4,007 were resistant to methicillin. Healthcare-associated infections accounted for 27.2% of cases and were associated with a significantly greater mortality rate, a longer length of stay, and greater hospital charges, compared with community-acquired infections. Patients with a complicated infection (78.4%) had a significantly greater mortality rate, a longer length of stay, and greater hospital charges, compared with patients with an uncomplicated infection. CONCLUSIONS. SSTBJ infections are frequent among hospitalized patients. S. aureus caused infection in more than 50% of the patients studied, and 28.0% of the S. aureus isolates recovered were resistant to methicillin. Healthcare-associated and complicated infections are associated with a significantly higher mortality rate and more prolonged and expensive hospitalizations. These findings could assist in projects to revise current management strategies in order to optimize outcomes while restraining costs. C1 Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. Med Coll Wisconsin, Milwaukee, WI USA. Cardinal Hlth Clin Res Grp, Marlborough, MA USA. RP Lipsky, BA (reprint author), Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. EM balipsky@u.washington.edu OI Lipsky, Benjamin A./0000-0001-9886-5114 NR 38 TC 69 Z9 72 U1 1 U2 3 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 2007 VL 28 IS 11 BP 1290 EP 1298 DI 10.1086/520743 PG 9 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 222OO UT WOS:000250307000012 PM 17926281 ER PT J AU Suppes, T Kelly, DI Keck, PE McElroy, SL Altshuler, LL Mintz, J Frye, MA Nolen, WA Luckenbaugh, DA Post, RM Leverich, GS Kupka, RW Grunze, H AF Suppes, Trisha Kelly, Dorothy I. Keck, Paul E., Jr. McElroy, Susan L. Altshuler, Lori L. Mintz, Jim Frye, Mark A. Nolen, Willem A. Luckenbaugh, David A. Post, Robert M. Leverich, Gabriele S. Kupka, Ralph W. Grunze, Heinz TI Quetiapine for the continuation treatment of bipolar depression: naturalistic prospective case series from the Stanley Bipolar Treatment Network SO INTERNATIONAL CLINICAL PSYCHOPHARMACOLOGY LA English DT Article DE bipolar disorder; bipolar depression; cycling; quetiapine ID TREATMENTS CANMAT GUIDELINES; PLACEBO-CONTROLLED TRIAL; I-DISORDER; DOUBLE-BLIND; ADJUNCTIVE QUETIAPINE; CANADIAN NETWORK; MOOD STABILIZER; FOLLOW-UP; OLANZAPINE; MAINTENANCE AB Continuation treatment for bipolar disorder often consists of a mood stabilizer and a second-generation antipsychotic. Quetiapine has been shown to be an effective treatment for acute mania and acute bipolar depression, but there are limited data for its use in continuation treatment. This study examined the effectiveness of open-label adjunctive quetiapine therapy for continuation treatment in patients with bipolar disorder. Prospectively collected life chart data from 63 outpatients with bipolar disorders, most recent episodes depressed, manic, or cycling, who received adjunctive quetiapine therapy as part of standard acute treatment were analyzed. Patients had 4 or more weeks of prequetiapine baseline data and at least 2 weeks of quetiapine treatment with no other medication changes. Patients were grouped by baseline symptoms; depression only, mania only, or both mania and depression (cycling group). Owing to small mania and well groups (n=4), differences between depression and cycling groups were examined and mania and well groups excluded. Fifty-five patients were included in the analyses. The primary outcome measure was change in mood severity from baseline to change in treatment regimen, as measured by the NIMH Life Charting Method. Patients received adjunctive quetiapine for a mean of 122 (SD=149) days. Both groups showed significant improvement in depression ratings and time spent depressed by week 10. Both groups showed significant improvement in overall mood. No between-group differences in improvement were found. Adjunctive quetiapine may be useful as continuation treatment in bipolar populations with both pure depressive and cycling symptoms. Further controlled studies are warranted. C1 Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX 75390 USA. Univ Cincinnati, Coll Med, Cincinnati, OH USA. Cincinnati Vet Affairs Med Ctr, Cincinnati, OH USA. VA Greater Los Angles Healthcare Syst, Los Angeles, CA USA. Univ Calif Los Angeles, Los Angeles, CA USA. Mayo Coll Med, Rochester, MI USA. Univ Groningen, Univ Med Ctr Groningen, Groningen, Netherlands. Penn State Coll Med, Hershey, PA USA. NIMH, NIH, New York, NY USA. Altrecht Inst Mental Hlth Care, Utrecht, Netherlands. Ludwig Maximilians Univ Munchen, Munich, Germany. RP Suppes, T (reprint author), Univ Texas, SW Med Ctr, Dept Psychiat, 5323 Harry Hines Blvd, Dallas, TX 75390 USA. EM Trisha.Suppes@UTSouthwestern.edu RI Nolen, Willem/E-9006-2014; Mintz, Jim/N-7385-2014 OI Mintz, Jim/0000-0002-8299-5851 FU NIMH NIH HHS [R01 MH079261] NR 32 TC 10 Z9 10 U1 2 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0268-1315 J9 INT CLIN PSYCHOPHARM JI Int. Clin. Psychopharmacol. PD NOV PY 2007 VL 22 IS 6 BP 376 EP 381 PG 6 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 222RP UT WOS:000250315000009 PM 17917557 ER PT J AU Hopwood, CJ Clarke, AN Perez, M AF Hopwood, Christopher J. Clarke, Analesa N. Perez, Marisol TI Pathoplasticity of bulimic features and interpersonal problems SO INTERNATIONAL JOURNAL OF EATING DISORDERS LA English DT Article DE interpersonal problems; bulimia; pathoplasticity; assessment; treatment matching ID EATING-DISORDERS; PERSONALITY-DISORDERS; DSM-III; NERVOSA; THERAPY; WOMEN; SELF; PSYCHOTHERAPY; DIAGNOSIS; SYMPTOMS AB Objective: Recent research suggests that interpersonal problems and some forms of psychopathology are pathoplastic, or that they mutually affect one another in nonetiological ways. in the current study, the pathoplasticity of bulimic features and interpersonal problems was tested. Method: Inventory of interpersonal Problems-64 data from 130 women with scores in the top quartile on the Bulimia scale of the Eating Disorder Inventory-2 from a sample of 517 college undergraduates were cluster analyzed. Age, weight, and scores on psychopathology scales were tested for mean differences across the four quadrants of the interpersonal problems circumplex. Results: Consistent with the pathoplasticity hypothesis, cluster means did not differ on external variables. Furthermore, bulimic features and interpersonal problems independently predicted depression in the total sample. Conclusion: The interpersonal problems reported in the current study suggest differential treatment process that could inform the therapeutic relationship and help prevent premature termination. (C) 2007 by Wiley Periodicals, Inc. C1 Texas A&M Univ, Dept Psychol, College Stn, TX 77843 USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Hopwood, CJ (reprint author), Texas A&M Univ, Dept Psychol, 4235 Psychol, College Stn, TX 77843 USA. EM chopwood@tamu.edu FU NIMH NIH HHS [F31 MH 75543-01A2] NR 43 TC 22 Z9 22 U1 4 U2 7 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0276-3478 J9 INT J EAT DISORDER JI Int. J. Eating Disord. PD NOV PY 2007 VL 40 IS 7 BP 652 EP 658 DI 10.1002/eat.20420 PG 7 WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology SC Psychology; Nutrition & Dietetics; Psychiatry GA 219VA UT WOS:000250115100010 PM 17610251 ER PT J AU Becker, AE AF Becker, Anne E. TI Culture and eating disorders classification SO INTERNATIONAL JOURNAL OF EATING DISORDERS LA English DT Article DE culture; ethnicity; diversity; classification; eating disorders ID HONG-KONG; ANOREXIA-NERVOSA; CHINESE PATIENTS; ADOLESCENT GIRLS; WHITE WOMEN; BODY-IMAGE; BLACK; TELEVISION; PREVALENCE; ETHNICITY AB objective: This paper discusses cultural considerations for classification of eating disorders. Method: The literature on epidemiology and phenomenology of eating disorders in culturally diverse populations was selectively reviewed to identify methodo-logic challenges in classification and characterization of prevalence and phenomenology. Results: Prevalence of eating disorders among culturally diverse populations is incompletely characterized. Few studies address the epidemiology of eating disorders or provide qualitative data on variation in presentation in these populations. Unrecognized cultural diversity may result in misclassification of cases. Conclusion: Development of culturally valid assessments, ethnographic data on indigenous nosologic correlates and idioms of distress, and attention to phenomenologic diversity may have critical impact on understanding clinical presentations and risk factors that may be culturally particular. A flexible classificatory system for the eating disorders may help to encompass their culturally based phenomenologic diversity, facilitate culturally sensitive and strategic prevention strategies, and reduce ethnic disparities in access to care for them. (c) 2007 by Wiley Periodicals, Inc. C1 Massachusetts Gen Hosp, Eating Disorders Clin & Res Program, Dept Psychiat, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Social Med, Boston, MA 02115 USA. RP Becker, AE (reprint author), Massachusetts Gen Hosp, Eating Disorders Clin & Res Program, Dept Psychiat, WAC 816C,15 parkman St, Boston, MA 02114 USA. EM abecker@partners.org NR 44 TC 11 Z9 11 U1 3 U2 14 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0276-3478 J9 INT J EAT DISORDER JI Int. J. Eating Disord. PD NOV PY 2007 VL 40 SU S BP S111 EP S116 DI 10.1002/eat.20435 PG 6 WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology SC Psychology; Nutrition & Dietetics; Psychiatry GA 221LS UT WOS:000250229900025 PM 17647276 ER PT J AU Eddy, KT Dorer, DJ Franko, DL Tahilani, K Thompson-Brenner, H Herzog, DB AF Eddy, Kamryn T. Dorer, David J. Franko, Debra L. Tahilani, Kavita Thompson-Brenner, Heather Herzog, David B. TI Should bulimia nervosa be subtyped by history of anorexia nervosa? A longitudinal validation SO INTERNATIONAL JOURNAL OF EATING DISORDERS LA English DT Article DE eating disorders; classification; longitudinal; crossover; recovery ID FOLLOW-UP; PREDICTORS; RECOVERY; RELAPSE; WOMEN AB Objective: To determine whether a past diagnosis of anorexia nervosa (AN) predicts longitudinal course and outcome among women with bulimia nervosa (BN). Method: A subset (n = 176) of participants in the Longitudinal Study of Anorexia and Bulimia Nervosa who met DSM-IV criteria for BN either at study intake (n = 144) or during follow-up (n = 32; 4 had restricting AN at intake, 28 had binge/purge AN at intake) were included in this report. Over a median of 9 years, weekly eating disorder symptom data were collected from participants using the Longitudinal Interview Followup Examination, Eating Disorders Version. Results: While there were no between-group differences in likelihood of partial recovery, women with BN who had a history of AN were more likely to have a protracted illness, relapsing into AN during follow-up, compared to those with no AN history who were more likely to move from partial to full recovery. Conclusion: Lifetime AN is an important prognostic indicator among women with BN and these longitudinal data would support the subtyping of BN on the basis of AN history. (c) 2007 by Wiley Periodicals, Inc. C1 Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Univ Chicago Hosp, Dept Psychiat, Chicago, IL 60637 USA. Boston Univ, Ctr Anxiety & Related Disorders, Boston, MA 02215 USA. Northeastern Univ, Dept Counseling & Appl Educ Psychol, Boston, MA 02115 USA. RP Eddy, KT (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. EM kamryn@bu.edu NR 15 TC 17 Z9 17 U1 3 U2 6 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0276-3478 J9 INT J EAT DISORDER JI Int. J. Eating Disord. PD NOV PY 2007 VL 40 SU S BP S67 EP S71 DI 10.1002/eat.20422 PG 5 WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology SC Psychology; Nutrition & Dietetics; Psychiatry GA 221LS UT WOS:000250229900015 PM 17610249 ER PT J AU Franko, DL AF Franko, Debra L. TI Race, ethnicity, and eating disorders: Considerations for DSM-V SO INTERNATIONAL JOURNAL OF EATING DISORDERS LA English DT Editorial Material ID AMERICAN WOMEN; SYMPTOMS C1 Northeastern Univ, Dept Counseling & Appl Educ Psychol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Harris Ctr Eating Disorders, Boston, MA 02114 USA. RP Franko, DL (reprint author), Northeastern Univ, Dept Counseling & Appl Educ Psychol, 203 Lake Hall, Boston, MA 02115 USA. EM d.franko@neu.edu NR 22 TC 10 Z9 10 U1 2 U2 8 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0276-3478 J9 INT J EAT DISORDER JI Int. J. Eating Disord. PD NOV PY 2007 VL 40 SU S BP S31 EP S34 DI 10.1002/eat.20455 PG 4 WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology SC Psychology; Nutrition & Dietetics; Psychiatry GA 221LS UT WOS:000250229900009 PM 17879288 ER PT J AU Habeenzu, C Mitarai, S Lubasi, D Mudenda, V Kantenga, T Mwansa, J Maslow, JN AF Habeenzu, C. Mitarai, S. Lubasi, D. Mudenda, V. Kantenga, T. Mwansa, J. Maslow, J. N. TI Tuberculosis and multidrug resistance in Zambian prisons, 2000-2001 SO INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE LA English DT Article DE prisons; tuberculosis; surveillance; Zambia ID PULMONARY TUBERCULOSIS; MALAWI; PREVALENCE; HIV; TB AB BACKGROUND: Data on prevalence of tuberculosis (TB) and multidrug-resistant tuberculosis (MDR-TB) in Zambian prisons are lacking. METHODS: Between January 2000 and July 2001, a case-finding study was performed in 13 Zambian prisons for pulmonary TB. Prisoners were administered a questionnaire to obtain demographic information. Information regarding housing density and diet was also collected. Three consecutive first morning sputum specimens were cultured for Mycobacterium tuberculosis. Antimicrobial resistance testing was performed by the resistance ratio method. RESULTS: A total of 10 8 0 prisoners were recruited: 105 5 were males and 25 females. Sputum from 245 (22.7%) prisoners yielded M. tuberculosis, including 168 (15.6%) with smear-positive disease. Based on a total prison population of 6118, the minimal prevalence of TB was 4.0%. There was a linear relationship between the proportion of prisoners evaluated and the prevalence of TB (R-2 = 0.9366) across facilities, suggesting that the true prevalence of TB may approach 15-20%. Resistance to at least one anti-tuberculosis drug was detected for 40 (23.8%) isolates, while MDR-TB was identified for 16 (9.5%) isolates. CONCLUSION: There is a high rate of pulmonary TB in Zambian prisons, with significant rates of drug resistance and MDR-TB, highlighting the need for active surveillance and treatment programs. C1 Univ Teaching Hosp, Dept Pathol & Microbiol, Lusaka, Zambia. Japan Int Cooperat Agcy, Tokyo, Japan. Univ Teaching Hosp, Ctr Infect Dis, TB Lab, Lusaka, Zambia. Univ Penn, Dept Vet Affairs Med Ctr, Div Infect Dis, Infect Dis Sect, Philadelphia, PA 19104 USA. RP Maslow, JN (reprint author), Dept Vet Affairs Med Ctr, Univ & Woodland Aves, Philadelphia, PA 19104 USA. EM joel.maslow@va.gov FU NIAID NIH HHS [5 U01 AI32783, AI450008] NR 16 TC 38 Z9 40 U1 0 U2 1 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 2007 VL 11 IS 11 BP 1216 EP 1220 PG 5 WC Infectious Diseases; Respiratory System SC Infectious Diseases; Respiratory System GA 230UL UT WOS:000250901400011 PM 17958984 ER PT J AU Weiss, JS Kruth, HS Kuivaniemi, H Tromp, G White, PS Winters, RS Lisch, W Henn, W Denninger, E Krause, M Wasson, P Ebenezer, N Mahurkar, S Nickerson, ML AF Weiss, Jayne S. Kruth, Howard S. Kuivaniemi, Helena Tromp, Gerard White, Peter S. Winters, R. Scott Lisch, Walter Henn, Wolfram Denninger, Elke Krause, Matthias Wasson, Paul Ebenezer, Neil Mahurkar, Sunil Nickerson, Michael L. TI Mutations in the UBIAD1 gene on chromosome short arm 1, region 36, cause schnyder crystalline corneal dystrophy SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID MONOCYTE-DERIVED MACROPHAGES; CHOLESTEROL EFFLUX; APOLIPOPROTEIN-E; TERE1; HYPERLIPOPROTEINEMIA; ASSOCIATION; METABOLISM; 1P34.1-P36; CARCINOMA; BLADDER AB PURPOSE. Schnyder crystalline corneal dystrophy ( SCCD; MIM 121800) is a rare autosomal dominant disease characterized by an abnormal increase in cholesterol and phospholipid deposition in the cornea, leading to progressive corneal opacification. Although SCCD has been mapped to a genetic interval between markers D1S1160 and D1S1635, reclassification of a previously unaffected individual expanded the interval to D1S2667 and included nine additional genes. Three candidate genes that may be involved in lipid metabolism and/or are expressed in the cornea were analyzed. METHODS. DNA samples were obtained from six families with clinically confirmed SCCD. Analysis of FRAP1, ANGPTL7, and UBIAD1 was performed by PCR-based DNA sequencing, to examine protein-coding regions, RNA splice junctions, and 5 ' untranslated region ( UTR) exons. RESULTS. No disease-causing mutations were found in the FRAP1 or ANGPTL7 gene. A mutation in UBIAD1 was identified in all six families: Five families had the same N102S mutation, and one family had a G177R mutation. Predictions of the protein structure indicated that a prenyl-transferase domain and several transmembrane helices are affected by these mutations. Each mutation cosegregated with the disease in four families with DNA samples from both affected and unaffected individuals. Mutations were not observed in 100 control DNA samples ( 200 chromosomes). CONCLUSIONS. Nonsynonymous mutations in the UBIAD1 gene were detected in six SCCD families, and a potential mutation hot spot was observed at amino acid N102. The mutations are expected to interfere with the function of the UBIAD1 protein, since they are located in highly conserved and structurally important domains. C1 Wayne State Univ, Sch Med, Kresge Eye Inst, Dept Ophthalmol, Detroit, MI 48201 USA. Wayne State Univ, Sch Med, Dept Surg, Detroit, MI 48201 USA. Wayne State Univ, Sch Med, Ctr Mol Med & Genet, Detroit, MI 48201 USA. NIH, Sect Expt Atherosclerosis, Bethesda, MD 20892 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Klinikum Hanau, Dept Ophthalmol, Hanau, Germany. Univ Saarland, Dept Human Genet, D-6650 Homburg, Germany. Univ Saarland, Dept Ophthalmol, D-6650 Homburg, Germany. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. UCL, Inst Ophthalmol, Dept Mol Genet, London, England. Transgenom, Gaithersburg, MD USA. RP Weiss, JS (reprint author), Wayne State Univ, Sch Med, Kresge Eye Inst, Dept Ophthalmol, 4717 St Antoine, Detroit, MI 48201 USA. EM jweiss@med.wayne.edu RI Tromp, Gerard/B-2677-2017; OI Tromp, Gerard/0000-0002-7761-0806; Kuivaniemi, Helena/0000-0001-5753-8766 FU NEI NIH HHS [EY12972] NR 39 TC 54 Z9 59 U1 0 U2 3 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD NOV PY 2007 VL 48 IS 11 BP 5007 EP 5012 DI 10.1167/iovs.07-0845 PG 6 WC Ophthalmology SC Ophthalmology GA 228MU UT WOS:000250734800022 PM 17962451 ER PT J AU Rohrer, B Guo, Y Kunchithapautham, K Gilkeson, GS AF Rohrer, Baerbel Guo, Yao Kunchithapautham, Kannan Gilkeson, Gary S. TI Eliminating complement factor D reduces photoreceptor susceptibility to light-induced damage SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID INDUCED RETINAL DEGENERATION; FACTOR-H POLYMORPHISM; 2 APOPTOTIC PATHWAYS; MACULAR DEGENERATION; CHOROIDAL NEOVASCULARIZATION; CELL-DEATH; ROD PHOTORECEPTORS; GENE-EXPRESSION; PHOTIC INJURY; RAT RETINAS AB PURPOSE. Genetic risk factors such as variations in complement factors H ( CFH) and B ( CFB) have been implicated in the etiology of age- related macular degeneration. It has been hypothesized that inadequate control of complement- driven inflammation may be a major factor in disease pathogenesis. The authors tested the involvement of the complement system in an experimental model for oxidative stress- mediated photoreceptor degeneration, the light- damage mouse model. METHODS. Changes in gene expression were assessed in BALB/ c retinas in response to constant- light ( CL) exposure using microarrays and real- time PCR. Susceptibility to CL exposure was tested in CFD-/- mice on a BALB/ c background. Eyes were analyzed using electrophysiologic and histologic techniques. RESULTS. Genes encoding for proteins involved in complement activation were significantly upregulated after CL. The altered gene profiles were similar to proteins accumulated in drusen and to genes identified in the retina and RPE/ choroid of patients with age- related macular degeneration. Cyclic- light reared CFD-/- and CFD-/- mice had indistinguishable rod function and number; however, after CL challenge, CFD-/- photoreceptors were significantly protected. CONCLUSIONS. These results suggest that rod degeneration in the CL- damaged retina involves the activity of the alternative complement pathway and that eliminating the alternative pathway is neuroprotective. Thus, the light damage albino mouse model may be a good model to study complement- mediated photoreceptor degeneration. C1 Med Univ S Carolina, Dept Ophthalmol, Charleston, SC 29425 USA. Med Univ S Carolina, Div Res, Dept Neurosci, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Med, Div Rheumatol & Immunol, Charleston, SC 29425 USA. Ralph H Johnson VAMC, Med Res Serv, Charleston, SC USA. RP Rohrer, B (reprint author), Med Univ S Carolina, Dept Ophthalmol, 167 Ashley Ave, Charleston, SC 29425 USA. EM rohrer@musc.edu FU NCI NIH HHS [R24 CA95841]; NCRR NIH HHS [RR16434, C06 RR015455]; NEI NIH HHS [EY13520, EY14793] NR 41 TC 52 Z9 53 U1 0 U2 10 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD NOV PY 2007 VL 48 IS 11 BP 5282 EP 5289 DI 10.1167/iovs.07-0282 PG 8 WC Ophthalmology SC Ophthalmology GA 228MU UT WOS:000250734800055 PM 17962484 ER PT J AU Rychert, D Saindon, S Placek, S Daskalakis, D Rosenberg, ES AF Rychert, Denna Saindon, Suzanne Placek, Sarah Daskalakis, Demetre Rosenberg, Eric S. TI Sequence variation occurs in CD4 Epitopes during early HIV infection SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article; Proceedings Paper CT 14th Conference on Retroviruses and Opportunistic Infections CY FEB 25-28, 2007 CL Los Angeles, CA DE acute HlV infection; CD4(+) T-cell response; viral; evolution ID HEPATITIS-C VIRUS; T-CELL RESPONSES; HYPERVARIABLE REGION; IMMUNE-RESPONSES; VIREMIA; RECOGNITION; PEPTIDES; PROTEIN; VARIANTS; TH1 AB Objective: To determine whether viral sequence variation occurs in HIV-specific CD4 epitopes during early HIV infection. Methods: Gag, Net, and integrase (Int) sequences were obtained from the plasma of 7 subjects identified during acute HIV-1 infection. Changes in the viral sequence were determined based on comparison of sequences obtained at 2 time points during early infection. Peptide-specific CD4(+) T-cell responses were measured at matched time points using interferon-gamma enzyme-linked immunosorbent spot assays to identify CD4 epitopes. Results: An average of 4 mutations were identified per subject. The majority of the mutations were nonsynonymous and resulted in a total of 6 amino acid changes in Gag, 7 changes in Nef, and 6 changes and a deletion in Int. Half of the sequence changes were within recognized CD4 epitopes. Mutations within CD4 epitopes were coincident with changes in the peptide-specific CD4 response. Conclusion: These data indicate that sequence variation occurs within recognized CD4 epitopes during early HIV infection. Furthermore, it suggests that mutations within HIV-specific CD4 epitopes may affect T helper cell function. C1 Massachusetts Gen Hosp, Dept Med, Infect Dis Div & Clin Microbiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. NYU, Sch Med, Div Infect Dis & Immunol, New York, NY USA. RP Rosenberg, ES (reprint author), Massachusetts Gen Hosp, Dept Med, Infect Dis Div & Clin Microbiol, J 504,55 Fruit St, Boston, MA 02114 USA. EM Erosenbergl@partners.org NR 25 TC 3 Z9 3 U1 0 U2 2 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 2007 VL 46 IS 3 BP 261 EP 267 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 226RZ UT WOS:000250607500001 ER PT J AU Hadigan, C Liebau, J Andersen, R Holalkere, NS Sahani, DV AF Hadigan, Colleen Liebau, James Andersen, Rebecca Holalkere, Nagaraj-Setry Sahani, Dushyant V. TI Magnetic resonance Spectroscopy of hepatic lipid content and associated risk factors in HIV infection SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HIV; steatosis; insulin resistance; visceral adiposity; metabolic syndrome ID HUMAN-IMMUNODEFICIENCY-VIRUS; NONALCOHOLIC FATTY LIVER; MULTICENTER AIDS COHORT; TRIGLYCERIDE CONTENT; INSULIN-RESISTANCE; ANTIRETROVIRAL THERAPY; METABOLIC SYNDROME; C VIRUS; ACCUMULATION; LIPODYSTROPHY AB Background: Liver-related illness is increasingly recognized as a source of morbidity in HIV-infiected patients. Fatty infiltration of the liver is potentially an important consequence of HIV and treatment with antiretroviral (ARV) therapy. Objective: The aim of the present study was to evaluate HIV-infected men and women for hepatic steatosis using noninvasive magnetic resonance spectroscopy (MRS) and to assess the relationship between liver fat content, insulin resistance, and other associated risk factors. Methods: We examined 33 consecutively recruited HIV-infected adults without specific referral for liver disease. Subjects with alcohol abuse within 3 years or end-stage liver disease were excluded. The primary clinical measures were hepatic fat content measured by MRS, homeostasis model for assessment of insulin resistance (HOMA-IR), and body fat distribution assessed by cross-sectional computed tomography. Results: We identified hepatic steatosis (liver fat content >= 5%) in 42% of subjects. Hepatic fat content was significantly correlated with HOMA-IR (r = 0.68, P < 0.0001) and increased visceral adiposity (r = 0.60, P < 0.001). Subjects with steatosis had significantly increased body mass index and alanine aminotransferase and triglyceride levels, with lower muscle attenuation (ie, increased intramuscular fat) compared to subjects without steatosis. However, steatosis was not related to duration of HIV, ARV exposure, or HCV coinfection. Conclusions: These data suggest that hepatic steatosis may be very common in HIV, not limited to those with HCV coinfection, and may play an important role in the metabolic profile among HIV-infected men and women. C1 NIAID, NIH, Immunoregulat Lab, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Program Nutr Metab, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Hadigan, C (reprint author), NIAID, NIH, Immunoregulat Lab, 10 Ctr Dr,Bldg 10,Rm 11C103, Bethesda, MD 20892 USA. EM hadiganc@niaid.nih.gov FU NCRR NIH HHS [M01-RR-01066]; NIDDK NIH HHS [P30 DK040561, K23 DK02844, P30 DK040561-11, P30-DK040561] NR 37 TC 32 Z9 33 U1 0 U2 2 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 2007 VL 46 IS 3 BP 312 EP 317 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 226RZ UT WOS:000250607500009 PM 17721396 ER PT J AU Holmes, WC Bilker, WB Wang, H Chapman, J Gross, R AF Holmes, William C. Bilker, Warren B. Wang, Hao Chapman, Jennifer Gross, Robert TI HIV/AIDS-Specific quality of life and adherence to Antiretroviral therapy over time SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE adherence; AIDS; HIV; quality of life ID HUMAN-IMMUNODEFICIENCY-VIRUS; MULTICENTER AIDS COHORT; SELF-REPORTED ADHERENCE; HIV-INFECTED ADULTS; HAT-QOL INSTRUMENT; MEDICATION ADHERENCE; VIRAL LOAD; UNITED-STATES; DRUG-USE; PREDICTORS AB Objective: To determine if HIV/AIDS-specific quality of life (QOL) predicts adherence to antiretroviral therapy (ART). Methods: HIV-infected outpatients on efavirenz plus 2 or 3 nucleoside analogue reverse transcriptase inhibitors and with HIV viral loads <75 copies/mL were followed until the censoring event of detectable viremia or 1 year of follow-up. QOL was assessed at baseline with the HIV/AIDS-Targeted Quality of Life instrument (HAT-QoL), as were depression symptoms, stress levels, social support, and substance use. Follow-up high (>= 95%) versus low (<95%) adherence was measured for 90 days before the censoring event. Results: Fifty-six (48%) of 116 recruited participants had low adherence. Baseline financial worries (from the HAT-QoL) were greater in those with low versus high adherence (P = 0.02). Those with low versus high adherence also were more likely to use alcohol (P = 0.01) and other drugs (P = 0.02) currently at baseline. Regression analysis led to a model that included only current alcohol use (odds ratio [OR] = 2.65, 95% confidence interval [Cl]: 1.20 to 5.87)) and financial worries (OR = 1.16, 95% CI: 1.03 to 1.310, for each 10-unit rise). Conclusions: Baseline financial worries were associated with antiretroviral adherence later in time. Questions about paying bills and financial ability to care for oneself may be clinically useful inidentifyinf patienst who will have suboptimal adherence. C1 Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Philadellphia Vet Affairs Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. Univ Penn, Sch Med, Dept Med, Div Gen Internal Med, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Med, Div Infect Dis, Philadelphia, PA 19104 USA. RP Holmes, WC (reprint author), Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, 733 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM holmeswc@mail.med.upenn.edu FU AHRQ HHS [HS10399]; NIAID NIH HHS [P30-AI45008]; NIMH NIH HHS [K08MH01584] NR 42 TC 28 Z9 29 U1 1 U2 6 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 2007 VL 46 IS 3 BP 323 EP 327 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 226RZ UT WOS:000250607500011 PM 17846560 ER PT J AU Yerevanian, BI Ralph, JK Mintz, J AF Yerevanian, Boghos I. Koek, Ralph J. Mintz, Jim TI Bipolar pharmacotherapy and suicidal behavior. Part I: Lithium, divalproex and carbamazepine SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE suicide; suicide attempt; lithium; divalproex; carbamazepine; bipolar disorder; veterans; longitudinal study; public health ID PRIMARY AFFECTIVE-DISORDERS; MOOD DISORDERS; RISK; MORTALITY; PREVENTION; REGISTER; TRIALS AB Introduction: The anti-suicidal benefit of lithium on suicidal behavior in bipolar disorder is well-established. Data are mixed on the effects of divalproex and carbamazepine. Methods: Retrospective chart review study of 405 veterans with bipolar disorder followed for a mean of 3 years, with month by month review of clinical progress notes, and systematic assessment of current pharmacotherapy and suicide completion, attempt or hospitalization for suicidality. Comparison of suicide event rates (events/100 patient years) between mood stabilizers and during-vs-after discontinuation of mood stabilizers, with linear regression analysis for influence of potential confounding variables, and robust bootstrap confirmation analysis. Results: No completed suicides occut red during or after discontinuation of monotherapy. Rates of non-lethal suicidal behavior were similar during lithium (2.49), divalproex (4.67) and carbamazepine (3.80) monotherapies. There was a sixteen fold greater, highly statistically significant non-lethal suicidal event rate after discontinuation compared with during mood stabilizer monotherapy (55.89 vs. 3.48 events/100 patient years,- Chi(2) = 13.95; df= 1; p < 0.0002). On compared with off treatment differences were similar for the three different agents. Limitations: Treatments were uncontrolled in this naturalistic setting, and data were analyzed retrospectively. Conclusions: Lithium and the anticonvulsants may show similar benefits in protecting bipolar patients from non-lethal suicidal behavior when careful analysis of clinical data is done to confirm medication adherence/non-adherence. Findings in this study were similar to those of a previous study that applied the same methodology in a private practice setting. Published by Elsevier B.V. C1 Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, David Geffen Sch Med, Los Angeles, CA 90024 USA. VA Greater Los Angeles Hlth Care Syst, Sepulveda Ambulatory Care Ctr, Los Angeles, CA 90073 USA. RP Yerevanian, BI (reprint author), 16111 Plummer St 116A-11, North Hills, CA 91343 USA. EM byerevan@ucla.edu NR 23 TC 45 Z9 49 U1 0 U2 2 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 2007 VL 103 IS 1-3 BP 5 EP 11 DI 10.1016/jjad.2007.05.019 PG 7 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 223UC UT WOS:000250396800002 PM 17628692 ER PT J AU Boghos, IY Koek, RJ Mintz, J Akiskal, HS AF Boghos, I. Yerevanian Koek, Ralph J. Mintz, Jim Akiskal, Hagop S. TI Bipolar pharmacotherapy and suicidal behavior - Part 2. The impact of antidepressants SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE suicide; suicide attempt; antidepressants; bipolar disorder; veterans; longitudinal study; public health ID WEEKLY SYMPTOMATIC STATUS; DEPRESSIVE MIXED STATES; STEP-BD; UNIPOLAR DEPRESSION; NATURAL-HISTORY; DISORDER; RISK; TRIALS; IDEATION; PROGRAM AB Antidepressant-induced mania and cycle acceleration is a potential risk in bipolar patients. Another serious risk of antidepressants, that of increasing suicidal behavior, has been identified in some affectively ill populations. However, there is a dearth of knowledge about the effects of antidepressants on suicidal behavior specifically in bipolar patients. Methods: Retrospective chart review of 405 veterans with bipolar disorder followed for a mean of three years, with month by month systematic assessment of current pharmacotherapy and suicide completion, attempt or hospitalization for suicidality. Chi-squared comparison of (log) rates of suicidal events during mood stabilizer monotherapy, antidepressant monotherapy, and combination of mood stabilizer and antidepressant. Results: Suicidal behavior event rates (per 100 patient years) were greatest during treatment with antidepressant monotherapy (25.92), least during mood stabilizer monotherapy (3.48), and intermediate during mood stabilizer + antidepressant combination treatment (9.75). These differences were statistically significant. Limitations: In a clinical setting, antidepressants may have been prescribed because patients were deemed at greater risk of suicidality. Conclusions: During treatment with antidepressants (even when coupled with mood stabilizers), patients with bipolar disorder have significantly higher rates of non-lethal suicidal behavior compared to those on mood stabilizers without antidepressants, and thus require careful monitoring. Published by Elsevier B.V. C1 Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, David Geffen Sch Med, North Hills, CA 91343 USA. VA Greater Los Angeles Hlth Care Syst, Sepulveda Ambulatory Care Ctr, Los Angeles, CA 90073 USA. Univ Calif San Diego, Int Mood Ctr, La Jolla, CA 92093 USA. Ctr Vet Med, La Jolla, CA USA. RP Boghos, IY (reprint author), Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, David Geffen Sch Med, 16111 Plummer St 116A-11, North Hills, CA 91343 USA. EM byerevan@ucla.edu NR 35 TC 0 Z9 0 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0327 EI 1573-2517 J9 J AFFECT DISORDERS JI J. Affect. Disord. PD NOV PY 2007 VL 103 IS 1-3 BP 13 EP 21 DI 10.1016/jjad.2007.05.017 PG 9 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 223UC UT WOS:000250396800003 ER PT J AU Yerevanian, BI Koek, RJ Mintz, J AF Yerevanian, Boghos I. Koek, Ralph J. Mintz, Jim TI Bipolar pharmacotherapy and suicidal behavior - Part 3: Impact of antipsychotics SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE suicide; suicide attempt; bipolar disorder; antipsychotic drugs; longitudinal study; public health ID PLACEBO-CONTROLLED TRIAL; ATYPICAL ANTIPSYCHOTICS; DISORDER; SCHIZOPHRENIA; DEPRESSION; RISK; ARIPIPRAZOLE; CLOZAPINE; IDEATION AB Introduction: Antipsychotics, particularly second generation agents, are widely used in bipolar disorder, but their effect on suicidal behavior in this population has not been systematically studied. Methods: Retrospective chart review of 405 veterans with bipolar disorder followed for a mean of three years, with month-by-month systematic assessment of current pharmacotherapy and suicide completion, attempt or hospitalization for suicidality. Comparison of rates of suicidal events during mood stabilizer monotherapy, antipsychotic monotherapy, and combination of mood stabilizer and antipsychotic. Results: Non-lethal suicide event rates were 9.4 times greater (x(2) =28.29, p<.0001) during antipsychotic monotherapy and 3.5 times greater during mood stabilizer+ antipsychotic (x(2) = 15.13, p=0.0001) than during mood stabilizer monotherapy. Limitations: Antipsychotics may have been prescribed because patients were at greater risk of suicidal behavior. First and second generation antipsychotics were not distinguished. Conclusions: Treatment of bipolar patients with antipsychotics is associated with an increase in non-lethal suicidal behavior. Thus, use of antipsychotics for bipolar patients requires careful monitoring for suicidal behavior. Further studies are urgently needed to better characterize this relationship. Published by Elsevier B.V. C1 Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, David Geffen Sch Med, North Hills, CA 91343 USA. VA Greater Los Angeles Hlth Care Syst, Sepulveda Ambulatory Care Ctr, Los Angeles, CA 90073 USA. RP Yerevanian, BI (reprint author), Univ Calif Los Angeles, Dept Psychiat & Biobehav Sci, David Geffen Sch Med, 16111 Plummer St 116A-11, North Hills, CA 91343 USA. EM byerevan@ucla.edu NR 24 TC 26 Z9 28 U1 0 U2 1 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 2007 VL 103 IS 1-3 BP 23 EP 28 DI 10.1016/jjad.2007.05.018 PG 6 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 223UC UT WOS:000250396800004 PM 17604119 ER PT J AU Morasco, BJ Rifai, MA Jennifer, ML Indest, DW Moles, JK Hauser, P AF Morasco, Benjamin J. Rifai, Muhamad Aly Jennifer, M. Loftis Indest, David W. Moles, James Kelly Hauser, Peter TI A randomized trial of paroxetine to prevent interferon-alpha-induced depression in patients with hepatitis C SO JOURNAL OF AFFECTIVE DISORDERS LA English DT Article DE depression; hepatitis c; prevention; viral response; antiviral therapy; interferon ID INDUCED MOOD DISORDER; PLUS RIBAVIRIN; MAJOR DEPRESSION; THERAPY; RISK; SYMPTOMS; NORTRIPTYLINE; COMORBIDITY; POPULATION; CITALOPRAM AB Background: Interferon-alpha-(IFN-alpha) induced depression presents a challenge when treating patients with the hepatitis C virus (HCV). Depression occurs in approximately one-third of patients during antiviral therapy and can lead to reduction in treatment dosage or discontinuation of treatment, thus reducing the likelihood of clearing HCV infection. This study examined the efficacy of paroxetine in preventing the development of depression during antiviral therapy. Methods: In a double-blind, placebo-controlled study, 33 patients with HCV were randomly assigned to paroxetine or placebo prior to antiviral therapy. Patients were evaluated for psychiatric symptoms prior, during, and six months after antiviral therapy. Results: The rate of IFN-alpha-induced depression for the entire sample was 33.3%. The prophylactic use of paroxetine did not decrease the likelihood of IFN-a-induced depression (35.7% in the paroxetine group vs. 31.6% in the placebo group). However, in 10 of 11 patients who developed IFN-alpha-induced depression and entered the rescue arm of the study, open-label treatment with paroxetine helped reduce symptoms of depression. Group assignment did not appear to impact antiviral therapy completion rates, as a similar proportion of patients from each group completed treatment. Limitations: The antiviral treatment was changed during the trial and aspects of the sample limit the general izabi lity of the results. Conclusion: A prophylactic approach to interferon-alpha-induced depression may not be indicated in patients with HCV infection. (C) 2007 Elsevier B.V. All rights reserved. C1 Portland VA Med Ctr, NW Hepatitis C Resource Ctr, Behav Hlth & Clin Neurosci Div, Portland, OR 97239 USA. Salem VA Med Ctr, Salem, VA 24153 USA. Univ Virginia, Sch Med, Roanoke Salem, VA USA. Oregon Hlth & Sci Univ, Dept Psychiat, Portland, OR 97201 USA. Portland VA Med Ctr, JENS Lab, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Dept Internal Med, Portland, OR 97201 USA. RP Hauser, P (reprint author), Portland VA Med Ctr, NW Hepatitis C Resource Ctr, Behav Hlth & Clin Neurosci Div, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. EM peter.hauser2@med.va.gov NR 49 TC 63 Z9 65 U1 0 U2 1 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 2007 VL 103 IS 1-3 BP 83 EP 90 DI 10.1016/j.jad.2007.01.007 PG 8 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 223UC UT WOS:000250396800010 PM 17292481 ER PT J AU Neimark, MA Konstas, AA Laine, AF Pile-Spellman, J AF Neimark, Matthew A. Konstas, Angelos-Aristeidis Laine, Andrew F. Pile-Spellman, John TI Integration of jugular venous return and circle of Willis in a theoretical human model of selective brain cooling SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE intracarotid saline infusion; intracerebral vascular flow rates; therapeutic hypothermia ID CEREBRAL-BLOOD-FLOW; HOSPITAL CARDIAC-ARREST; MODERATE HYPOTHERMIA; SALINE INFUSION; ACUTE STROKE; HYPERVOLEMIC HEMODILUTION; THERAPEUTIC HYPOTHERMIA; CRYSTALLOID INFUSION; COMATOSE SURVIVORS; MILD HYPOTHERMIA AB A three- dimensional mathematical model was developed to examine the induction of selective brain cooling ( SBC) in the human brain by intracarotid cold (2.8 degrees C) saline infusion ( ICSI) at 30 ml/ min. The Pennes bioheat equation was used to propagate brain temperature. The effect of cooled jugular venous return was investigated, along with the effect of the circle of Willis ( CoW) on the intracerebral temperature distribution. The complete CoW, missing A1 variant ( mA1), and fetal P1 variant ( fP1) were simulated. ICSI induced moderate hypothermia ( defined as 32 - 34 C) in the internal carotid artery ( ICA) territory within 5 min. Incorporation of the complete CoW resulted in a similar level of hypothermia in the ICA territory. In addition, the anterior communicating artery and ipsilateral posterior communicating artery distributed cool blood to the contralateral anterior and ipsilateral posterior territories, respectively, imparting mild hypothermia (35 and 35.5 degrees C respectively). The mA1 and fP1 variants allowed for sufficient cooling of the middle cerebral territory (30 - 32 degrees C). The simulations suggest that ICSI is feasible and may be the fastest method of inducing hypothermia. Moreover, the effect of convective heat transfer via the complete CoW and its variants underlies the important role of CoW anatomy in intracerebral temperature distributions during SBC. C1 Columbia Univ, Dept Biomed Engn, New York, NY 10027 USA. Columbia Univ, Dept Radiol, New York, NY 10027 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Neimark, MA (reprint author), Columbia Univ, Dept Biomed Engn, 1210 Amsterdam Ave, New York, NY 10027 USA. EM man2003@columbia.edu NR 59 TC 9 Z9 11 U1 0 U2 5 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 2007 VL 103 IS 5 BP 1837 EP 1847 DI 10.1152/japplphysiol.00542.2007 PG 11 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 224WZ UT WOS:000250480400046 PM 17761787 ER PT J AU Kuchma, SL Brothers, KM Merritt, JH Liberati, NT Ausubel, FM O'Toole, GA AF Kuchma, Sherry L. Brothers, Kimberly M. Merritt, Judith H. Liberati, Nicole T. Ausubel, Frederick M. O'Toole, George A. TI BifA, a cyclic-di-GMP phosphodiesterase, inversely regulates biofilm formation and swarming motility by Pseudomonas aeruginosa PA14 SO JOURNAL OF BACTERIOLOGY LA English DT Article ID GRAM-NEGATIVE BACTERIA; TWITCHING MOTILITY; FLUORESCENS WCS365; IRREVERSIBLE ATTACHMENT; ACETOBACTER-XYLINUM; SECRETED PROTEIN; DOMAIN PROTEIN; PAO1 BIOFILM; EAL DOMAINS; SYSTEM AB The intracellular signaling molecule, cyclic-di-GMP (c-di-GMP), has been shown to influence bacterial behaviors, including motility and biofilm formation. We report the identification and characterization of PA4367, a gene involved in regulating surface-associated behaviors in Pseudomonas aeruginosa. The PA4367 gene encodes a protein with an EAL domain, associated with c-di-GMP phosphodiesterase activity, as well as a GGDEF domain, which is associated with a c-di-GMP-synthesizing diguanylate cyclase activity. Deletion of the PA4367 gene results in a severe defect in swarming motility and a hyperbiofilm phenotype; thus, we designate this gene bifA, for biofilm formation. We show that BifA localizes to the inner membrane and, in biochemical studies, that purified BifA protein exhibits phosphodiesterase activity in vitro but no detectable diguanylate cyclase activity. Furthermore, mutational analyses of the conserved EAL and GGDEF residues of BifA suggest that both domains are important for the observed phosphodiesterase activity. Consistent with these data, the Delta bifA mutant exhibits increased cellular pools of c-di-GMP relative to the wild type and increased synthesis of a polysaccharide produced by the pel locus. This increased polysaccharide production is required for the enhanced biofilm formed by the Delta bifA mutant but does not contribute to the observed swarming defect. The Delta bifA mutation also results in decreased flagellar reversals. Based on epistasis studies with the previously described sadB gene, we propose that BifA functions upstream of SadB in the control of biofilm formation and swarming. C1 Dartmouth Coll, Sch Med, Dept Microbiol & Immunol, Hanover, NH 03755 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. RP O'Toole, GA (reprint author), Dartmouth Coll, Sch Med, Dept Microbiol & Immunol, Rm 505,Vail Bldg,N Coll St, Hanover, NH 03755 USA. EM georgeo@dartmouth.edu FU NCRR NIH HHS [1-P20-RR01878]; NIAID NIH HHS [AI51360, R01 AI051360, R01 AI083256] NR 56 TC 161 Z9 166 U1 1 U2 18 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD NOV PY 2007 VL 189 IS 22 BP 8165 EP 8178 DI 10.1128/JB.00586-07 PG 14 WC Microbiology SC Microbiology GA 232AU UT WOS:000250991300026 PM 17586641 ER PT J AU Lee, H Alt, C Pitsillides, CM Lin, CP AF Lee, Ho Alt, Clemens Pitsillides, Costas M. Lin, Charles P. TI Optical detection of intracellular cavitation during selective laser targeting of the retinal pigment epithelium: dependence of cell death mechanism on pulse duration SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE laser; cell targeting; intracellular cavitation; retinal pigment epithelium; laser-induced cell death ID HEATED MICROPARTICLES; TIME REGIMEN; PHOTOCOAGULATION; INJURY; BEAM; RPE; MICROCAVITATION; NANOSECOND; ABSORPTION; RADIATION AB Selective laser targeting of the retinal pigment epithelium (RPE) is an attractive method for treating RPE-associated disorders. We are developing a method for optically detecting intracellular micro-cavitation that can potentially serve as an immediate feedback of the treatment outcome. Thermal denaturation or intracellular cavitation can kill RPE cells during selective targeting. We examined the cell damage mechanism for laser pulse durations from 1 to 40 mu s ex vivo. Intracellular cavitation was detected as a transient increase in the backscattered treatment beam. Cavitation and cell death were correlated for individual cells after single-pulse irradiation. The threshold radiant exposures for cell death (ED(50,d)) and cavitation (ED(50,c)) increased with pulse duration and were approximately equal for pulses of up to 10 mu s. For 20 mu s, the ED(50,d) was about 10% lower than the ED(50,c); the difference increased with 40-mu s pulses. Cells were killed predominantly by cavitation (up to 10-mu s pulses); probability of thermally induced cell death without cavitation gradually increases with pulse duration. Threshold measurements are discussed by modeling the temperature distribution around laser-heated melanosomes and the scattering function from the resulting cavitation. Detection of intracellular cavitation is a highly sensitive method that can potentially provide real-time assessment of RPE damage during selective laser targeting. (C) 2007 Society of Photo-Optical Instrumentation Engineers. C1 [Lee, Ho; Alt, Clemens; Pitsillides, Costas M.; Lin, Charles P.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Lee, Ho; Alt, Clemens; Pitsillides, Costas M.; Lin, Charles P.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Lee, Ho] Kyungpook Natl Univ, Sch Mech Engn, Taegu 701702, South Korea. [Alt, Clemens] Tufts Univ, Dept Biomed Engn, Boston, MA 02114 USA. [Pitsillides, Costas M.] Boston Univ, Dept Biomed Engn, Boston, MA 02114 USA. RP Lin, CP (reprint author), CPZN 8238,185 Cambridge St, Boston, MA 02114 USA. EM lin@helix.mgh.harvard.edu FU NEI NIH HHS [EY-12970] NR 45 TC 23 Z9 24 U1 0 U2 3 PU SPIE-SOC PHOTO-OPTICAL 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 2007 VL 12 IS 6 AR 064034 DI 10.1117/1.2804078 PG 14 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 258EL UT WOS:000252851100055 PM 18163850 ER PT J AU Yelin, R Yelin, D Oh, WY Yun, SH Boudoux, C Vakoc, BJ Bouma, BE Tearney, GJ AF Yelin, Ronit Yelin, Dvir Oh, Wang-Yuhl Yun, Seok H. Boudoux, Caroline Vakoc, Benjamin J. Bouma, Brett E. Tearney, Guillermo J. TI Multimodality optical imaging of embryonic heart microstructure SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE optical imaging; four-dimensional imaging; fetal alcohol syndrome; heart imaging; Xenopus laevis ID ENCODED CONFOCAL MICROSCOPY; FETAL ALCOHOL SYNDROME; COHERENCE TOMOGRAPHY; XENOPUS-LAEVIS; HIGH-SPEED; CARDIOVASCULAR-SYSTEM; CARDIAC DEVELOPMENT; MODEL SYSTEMS; SWEPT SOURCE; EXPOSURE AB Study of developmental heart defects requires the visualization of the microstructure and function of the embryonic myocardium, ideally with minimal alterations to the specimen. We demonstrate multiple endogenous contrast optical techniques for imaging the Xenopus laevis tadpole heart. Each technique provides distinct and complementary imaging capabilities, including: 1.3-D coherence microscopy with subcellular (1 to 2 mu m) resolution in fixed embryos, 2. real-time reflectance confocal microscopy with large penetration depth in vivo, and 3. ultra-high speed (up to 900 frames per second) that enables real-time 4-D high resolution imaging in vivo. These imaging modalities can provide a comprehensive picture of the morphologic and dynamic phenotype of the embryonic heart. The potential of endogenous-contrast optical microscopy is demonstrated for investigation of the teratogenic effects of ethanol. Microstructural abnormalities associated with high levels of ethanol exposure are observed, including compromised heart looping and loss of ventricular trabecular mass. (C) 2007 Society of Photo-Optical Instrumentation Engineers. C1 [Yelin, Ronit; Yelin, Dvir; Oh, Wang-Yuhl; Yun, Seok H.; Boudoux, Caroline; Vakoc, Benjamin J.; Bouma, Brett E.; Tearney, Guillermo J.] Harvard Univ, Wellman Ctr Photomed, Sch Med, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Tearney, GJ (reprint author), Harvard Univ, Wellman Ctr Photomed, Sch Med, Massachusetts Gen Hosp, 55 Fruit St,BAR703, Boston, MA 02114 USA. EM gtearney@partners.org RI Oh, Wang-Yuhl/C-2055-2011; Boudoux, Caroline/A-6399-2012 FU NHLBI NIH HHS [R01 HL076398-03, R01 HL076398] NR 58 TC 16 Z9 16 U1 0 U2 5 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 2007 VL 12 IS 6 AR 064021 DI 10.1117/1.2822904 PG 12 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 258EL UT WOS:000252851100042 PM 18163837 ER PT J AU Zhang, Q Brown, EN Strangman, GE AF Zhang, Quan Brown, Emery N. Strangman, Gary E. TI Adaptive filtering to reduce global interference in evoked brain activity detection: a human subject case study SO JOURNAL OF BIOMEDICAL OPTICS LA English DT Article DE near infrared; brain; visual cortex; function; hemodynamics; adaptive filter; interference; cancellation ID NEAR-INFRARED SPECTROSCOPY; CEREBRAL HEMODYNAMICS; CEREBROVASCULAR RESPONSE; OPTICAL SPECTROSCOPY; COGNITIVE TASKS; FOCAL CHANGES; HUMAN ADULTS; OXYGENATION; TOMOGRAPHY; ACTIVATION AB Following previous Monte Carlo simulations, we describe in detail an example of detecting evoked visual hemodynamic responses in a human subject as a preliminary demonstration of the novel global interference cancellation technology. The raw time series of oxyhemoglobin (O(2)Hb) and deoxyhemoglobin (HHb) changes, their block averaged results before and after adaptive filtering, together with the power spectral density analysis are presented. Simultaneous respiration and EKG recordings suggested that spontaneous low-frequency oscillation and cardiac activity were the major sources of global interference in our test. When global interference dominates (e.g., for O(2)Hb in our data, judged by power spectral density analysis), adaptive filtering effectively reduced this interference, doubling the contrast-to-noise ratio (CNR) for evoked visual response detection. When global interference is not obvious (e.g., in our HHb data), adaptive filtering provided no CNR improvement. The results also showed that the hemodynamic changes in the superficial layers and the estimated total global interference in the target measurement were highly correlated (r = 0.96), which explains why this global interference cancellation method should work well when global interference is dominating. In addition, the results suggested that association between the superficial layer hemodynamics and the total global interference is time-varying. (C) 2007 Society of Photo-Optical Instrumentation Engineers. C1 [Zhang, Quan; Strangman, Gary E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neural Syst Grp, Charlestown, MA 02129 USA. [Brown, Emery N.] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Harvard Mit Div Hlth Sci & Technol, MIT, Boston, MA 02114 USA. RP Zhang, Q (reprint author), Neural Syst Grp, MGH Bldg 149,13th St,Rm 2651, Charlestown, MA 02129 USA. EM qzhang@nmr.mgh.harvard.edu FU NIBIB NIH HHS [R01-EB006589, R21-EB02416]; NIDA NIH HHS [R01-DA015644]; NINDS NIH HHS [K25-NS46554] NR 41 TC 60 Z9 60 U1 0 U2 6 PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA SN 1083-3668 EI 1560-2281 J9 J BIOMED OPT JI J. Biomed. Opt. PD NOV-DEC PY 2007 VL 12 IS 6 AR 064009 DI 10.1117/1.2804706 PG 12 WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine & Medical Imaging GA 258EL UT WOS:000252851100030 PM 18163825 ER PT J AU Hariri, S Bozic, KJ Lavernia, C Prestipino, A Rubash, HE AF Hariri, Sanaz Bozic, Kevin J. Lavernia, Carlos Prestipino, Ann Rubash, Harry E. TI Medicare physician reimbursement: Past, present, and future SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Editorial Material ID RESOURCE; ARTHROPLASTY C1 Massachusetts Gen Hosp, Dept Orthopaed Surg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Surg & Clin Business Dev, Boston, MA 02114 USA. Univ Calif San Francisco, Dept Orthopaed Surg, San Francisco, CA 94143 USA. Mercy Hosp, Inst Orthopaed, Coconut Grove, FL 33133 USA. RP Hariri, S (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, 55 Fruit St,YCOC Suite 3700, Boston, MA 02114 USA. EM shariri@partners.org; aprestipino@partners.org; hrubash@partners.org NR 47 TC 25 Z9 25 U1 0 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 2007 VL 89A IS 11 BP 2536 EP 2546 DI 10.2106/JBJS.F.00697 PG 11 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 228KE UT WOS:000250728000031 PM 17974898 ER PT J AU Solomon, DH Katz, JN Finkelstein, JS Polinski, JM Stedman, M Brookhart, MA Arnold, M Gauthier, S Avorn, J AF Solomon, Daniel H. Katz, Jeffrey N. Finkelstein, Joel S. Polinski, Jennifer M. Stedman, Margaret Brookhart, M. Alan Arnold, Marilyn Gauthier, Suzanne Avorn, Jerry TI Osteoporosis improvement: A large-scale randomized controlled trial of patient and primary care physician education SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE osteoporosis; randomized controlled trial; factorial design; quality improvement; patient education ID INTERVENTIONS; FRACTURE; OUTREACH; GUIDELINES; PATTERNS; RATES AB We conducted a randomized controlled trial within the setting of a large drug benefit plan for Medicare beneficiaries. Primary care physicians and their patients were randomized to usual care, patient intervention only, physician intervention only, or both interventions. There was no difference in the probability of the primary composite endpoint (BMD test or osteoporosis medication) or in either of its components comparing the combined intervention group with usual care (risk ratio = 1.04; 95% CI, 0.85-1.26). Introduction: Fractures from osteoporosis are associated with substantial morbidity, mortality, and cost. However, only a minority of at-risk older adults receives screening and/or treatment for this condition. We evaluated the effect of educational interventions for osteoporosis targeting at-risk patients, primary care physicians, or both. Materials and Methods: We conducted a randomized controlled trial within the setting of a large drug benefit plan for Medicare beneficiaries. Primary care physicians and their patients were randomized to usual care, patient intervention only, physician intervention only, or both interventions. The at-risk patients were women >= 65 yr of age, men and women >= 65 yr of age with a prior fracture, and men and women; >= 65 yr of age who used oral glucocorticoids. The primary outcome studied was a composite of either undergoing a BMD test or initiating a medication used for osteoporosis. The secondary outcome was a hip, humerus, spine, or wrist fracture. Results: We randomized 828 primary care physicians and their 13,455 eligible at-risk patients into four study arms. Physician and patient characteristics were very similar across all four groups. Across all four groups, the rate of the composite outcome was 10.3 per 100 person-years and did not differ between the usual care and the combined intervention groups (p = 0.5). In adjusted Cox proportional hazards models, there was no difference in the probability of the primary composite endpoint comparing the combined intervention group with usual care (risk ratio = 1.04; 95% Cl, 0.85-1.26). There was also no difference in either of the components of the composite endpoint. The probability of fracture during follow-up was 4.2 per 100 person-years and did not differ by treatment assignment (P = 0.9). Conclusions: In this trial, a relatively brief program of patient and/or physician education did not work to improve the management of osteoporosis. More intensive efforts should be considered for future quality improvement programs for osteoporosis. C1 Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol, Boston, MA 02120 USA. Brigham & Womens Hosp, Dept Med, Div Rheumatol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Orthoped Surg, Boston, MA 02115 USA. Massachusetts Gen Hosp, Dept Med, Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Social Med, Boston, MA 02115 USA. Arthritis Fdn, Newton, MA USA. RP Solomon, DH (reprint author), Brigham & Womens Hosp, Dept Med, Div Pharmacoepidemiol, 1620 Tremont St,Suite 3030, Boston, MA 02120 USA. EM dhsolomon@partners.org OI Stedman, Margaret/0000-0001-9271-8332 FU NIAMS NIH HHS [AR48616] NR 24 TC 29 Z9 29 U1 1 U2 1 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD NOV PY 2007 VL 22 IS 11 BP 1808 EP 1815 DI 10.1359/JBMR.070717 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 228YJ UT WOS:000250768200021 PM 17645403 ER PT J AU Greenhalgh, DG Saffle, JR Holmes, JH Gamelli, RL Palmieri, TL Horton, JW Tompkins, RG Traber, DL Mozingo, DW Deitch, EA Goodwin, CW Herndon, DN Gallagher, JJ Sanford, AP Jeng, JC Ahrenholz, DH Neely, AN O'Mara, MS Wolf, SE Purdue, GF Garner, WL Yowler, CJ Latenser, BA AF Greenhalgh, David G. Saffle, Jeffrey R. Holmes, James H. Gamelli, Richard L. Palmieri, Tina L. Horton, Jureta W. Tompkins, Ronald G. Traber, Daniel L. Mozingo, David W. Deitch, Edwin A. Goodwin, Cleon W. Herndon, David N. Gallagher, James J. Sanford, Art P. Jeng, James C. Ahrenholz, David H. Neely, Alice N. O'Mara, Michael S. Wolf, Steven E. Purdue, Gary F. Garner, Warren L. Yowler, Charles J. Latenser, Barbara A. CA Amer Burn Ass Consensus Conf Burn TI American burn association consensus conference to define sepsis and infection in burns SO JOURNAL OF BURN CARE & RESEARCH LA English DT Article ID INFLAMMATORY RESPONSE SYNDROME; MULTIPLE ORGAN DYSFUNCTION; INTENSIVE-CARE-UNIT; RESPIRATORY-DISTRESS-SYNDROME; VENOUS CATHETER SEPSIS; BLOOD CULTURES; NOSOCOMIAL INFECTIONS; WOUND INFECTIONS; SOFA SCORE; BRONCHOALVEOLAR LAVAGE AB Because of their extensive wounds, burn patients are chronically exposed to inflammatory mediators. Thus, burn patients, by definition, already have "systemic inflammatory response syndrome." Current definitions for sepsis and infection have many criteria (fever, tachycardia, tachypnea, leukocytosis) that are routinely found in patients with extensive burns, making these current definitions less applicable to the burn population. Experts in burn care and research, all members of the American Burn Association, were asked to review the literature and prepare a potential definition on one topic related to sepsis or infection in burn patients. On January 20, 2007, the participants met in Tucson, Arizona to develop consensus for these definitions. After review of the definitions, a summary of the proceedings was prepared. The goal of the consensus conference was to develop and publish standardized definitions for sepsis and infection-related diagnoses in the burn population. Standardized definitions will improve the capability of performing more meaningful multicenter trials among burn centers. C1 Univ Calif Davis, Dept Surg, Sacramento, CA 95817 USA. Shriners Hosp Children No Calif, Sacramento, CA 95817 USA. Univ Utah, Dept Surg, Salt Lake City, UT USA. Wake Forest Univ, Bowman Gray Sch Med, Dept Surg, Winston Salem, NC 27103 USA. Loyola Univ, Dept Surg, Maywood, IL 60153 USA. Univ Texas, Dept Surg, Dallas, TX 75230 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. Shriners Hosp Children Boston, Boston, MA USA. Univ Texas, Med Branch, Dept Surg, Galveston, TX 77555 USA. Shriners Hosp Children Galveston, Galveston, TX USA. Univ Florida, Dept Surg, Gainesville, FL USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Surg, Newark, NJ 07103 USA. N Colorado Med Ctr, Dept Surg, Greeley, CO USA. Washington Hosp Ctr, Burn Ctr, Dept Surg, Washington, DC 20010 USA. Reg Hosp, Dept Surg, St Paul, MN USA. Shriners Hosp Children Cincinnati, Cincinnati, OH USA. Univ Cincinnati, Dept Surg, Cincinnati, OH 45221 USA. Univ Texas, Hlth Sci Ctr, Dept Surg, San Antonio, TX 78284 USA. Univ So Calif, Med Ctr, Dept Plast Surg, Los Angeles, CA USA. Case Western Reserve Univ, Metro Hlth Med Ctr, Dept Surg, Cleveland, OH 44106 USA. Univ Iowa, Dept Surg, Iowa City, IA 52242 USA. RP Greenhalgh, DG (reprint author), Univ Calif Davis, Dept Surg, 2425 Stockton Blvd, Sacramento, CA 95817 USA. OI O'Mara, Michael/0000-0001-7900-3949; Wolf, Steven/0000-0003-2972-3440 NR 96 TC 182 Z9 195 U1 4 U2 17 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1559-047X J9 J BURN CARE RES JI J. Burn Care Res. PD NOV-DEC PY 2007 VL 28 IS 6 BP 776 EP 790 DI 10.1097/BCR.0b013e3181599bc9 PG 15 WC Emergency Medicine; Dermatology; Surgery SC Emergency Medicine; Dermatology; Surgery GA 230JZ UT WOS:000250874100002 PM 17925660 ER PT J AU Moorman, AJ Mozaffarian, D Wilkinson, CW Lawler, RL Mcdonald, GB Crane, BA Spertus, JA Russo, JE Stempien-Otero, AS Sullivan, MD Levy, WC AF Moorman, Alec J. Mozaffarian, Dariush Wilkinson, Charles W. Lawler, Richard L. Mcdonald, George B. Crane, Barbara A. Spertus, John A. Russo, Joan E. Stempien-Otero, April S. Sullivan, Mark D. Levy, Wayne C. TI In patients with heart failure elevated soluble TNF-receptor 1 is associated with higher risk of depression SO JOURNAL OF CARDIAC FAILURE LA English DT Article DE heart failure; depression; cytokines; inflammation ID HEALTH-STATUS; SYSTEMIC INFLAMMATION; MAJOR DEPRESSION; RATING-SCALE; CYTOKINES; SYMPTOMS; TRANSPLANT; MEDIATORS; DISEASE; DEATH AB Background: Pro-inflammatory cytokines may contribute to the development and progression of heart failure (HF) and are also implicated in depressive disorders. In this cross-sectional study, we investigated whether systemic inflammation, as assessed by circulating levels of inflammatory cytokines, was associated with comorbid depression in patients with heart failure. Methods and Results: Baseline clinical variables, depression status, and inflammatory marker levels were measured in 129 ambulatory HF patients. We hypothesized that pro-inflammatory cytokines, specifically tumor necrosis factor (TNF)-alpha, interleukin (IL)-1, and IL-6, would be elevated in HF patients with comorbid depression. In unadjusted analyses, levels of soluble TNF-alpha receptor1 (sTNFr1) were significantly higher among depressed (1.6 ng/mL), compared with nondepressed (1.1 ng/mL), HF patients (P = .01). After multivariate adjustment, compared with patients in the lowest quartile of sTNFr1 levels, those in the highest quartile had an adjusted near 5-fold higher risk of depression (OR 4.6, 95% CI 1.2-17.3; P for trend .008). The subgroup of patients on antidepressants but not currently depressed had a trend toward higher levels of sTNFr1, suggesting that antidepressants may not lower cytokine levels even when adequately treating depressive symptoms. IL-10 and IL-6 levels were not significantly different among depressed versus nondepressed HF patients. Conclusions: In this cross-sectional analysis, HF patients with comorbid depression, compared with nondepressed HF patients, had higher levels of sTNFr1 and trend toward higher levels of sTNFr1 even when adequately treated for depression. C1 [Moorman, Alec J.; Crane, Barbara A.; Russo, Joan E.; Stempien-Otero, April S.; Sullivan, Mark D.; Levy, Wayne C.] Univ Washington, Dept Internal Med, Dept Psychiat & Behav Sci, Div Cardiol, Seattle, WA USA. [Mozaffarian, Dariush] Brigham & Womens Hosp, Harvard Med Sch, Harvard Sch Publ Hlth, Boston, MA 02115 USA. [Wilkinson, Charles W.] Univ Washington, Educ & Clin Ctr, Vet Affairs Puget Sound Hlth Care Syst, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Lawler, Richard L.; Mcdonald, George B.] Fred Hutchinson Canc Res Ctr, Gastroenterol Hepatol Sect, Seattle, WA 98104 USA. [Spertus, John A.] Univ Missouri, Mid Amer Heart Inst Ctr, Kansas City, KS USA. RP Levy, WC (reprint author), Univ Washington, 1959 NE Pacific St, Seattle, WA 98195 USA. RI Mozaffarian, Dariush/B-2276-2008 FU NCI NIH HHS [CA18029]; NCRR NIH HHS [M01-RR-00037] NR 25 TC 30 Z9 31 U1 1 U2 2 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 1071-9164 J9 J CARD FAIL JI J. Card. Fail. PD NOV PY 2007 VL 13 IS 9 BP 738 EP 743 DI 10.1016/j.cardfail.2007.06.301 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 240NB UT WOS:000251593200008 PM 17996822 ER PT J AU D'Avila, A Neuzil, P Thiagalingam, A Gutierrez, P Aleong, R Ruskin, JN Reddy, VY AF D'Avila, Andre Neuzil, Petr Thiagalingam, Aravinda Gutierrez, Paulo Aleong, Ryan Ruskin, Jeremy N. Reddy, Vivek Y. TI Experimental efficacy of pericardial instillation of anti-inflammatory agents during percutaneous epicardial catheter ablation to prevent postprocedure pericarditis SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Article; Proceedings Paper CT 28th Annual Scientific Session of the Heart-Rhythm-Society CY MAY 10, 2007 CL Denver, CO SP Heart Rhythm Soc DE catheter ablation; epicardium; radiofrequency; pericarditis ID RECURRENT VENTRICULAR-TACHYCARDIA; DILATED CARDIOMYOPATHY; TRIAMCINOLONE; TISSUE AB Introduction: Pericarditis is a potential complication of catheter-based percutaneous epicardial mapping and ablation. This study evaluates the efficacy and safety of intrapericardial instillation of anti-inflammatory agents after pericardial mapping and ablation in a porcine model of postprocedural pericarditis. Methods and Results: Twenty-five healthy swine underwent epicardial mapping and ablation after transthoracic subxyphoid puncture. After 60 minutes of continuous catheter manipulation in the pericardial space, radiofrequency energy was delivered in a linear fashion to the epicardial surfaces of both atria. The animals were randomly divided to receive the anti-inflammatory agents, Hyaluronic Acid and Triamcinolone, or control. Fourteen days after ablation, the hearts were excised and the degree of pericardial reaction/adhesions scored. The severity was uniformly graded 4 (intense) in all control animals and was characterized by intense adhesion between the parietal and the visceral pericardium obscuring tissue planes and epicardial anatomy. Hyaluronic Acid provided a mild benefit (score 3.0 +/- 0.9), but 2 mg/kg of Triamcinolone significantly attenuated the inflammatory effect (all animals uniformly scored 1.0). Conclusion: In a porcine model of ablation-related pericarditis, intrapericardial instillation of 2 mg/kg of intermediate-acting corticosteroids effectively prevents post-procedure inflammatory adhesion formation. C1 Harvard Univ, Sch Med, Boston, MA USA. Na Homolka Hosp, Cardiac Arrhythmia Unit, Prague, Czech Republic. Univ Sao Paulo, Inst Heart, Unit Pathol, Sao Paulo, Brazil. RP D'Avila, A (reprint author), Massachusetts Gen Hosp, Cardiac Arrhtymia Serv, 55 Fruit St GRB 109, Boston, MA 02114 USA. EM adavila@partners.org RI d'Avila, Andre Luiz/F-8009-2010; d'Avila, Andre/A-7693-2009 OI d'Avila, Andre Luiz/0000-0001-8769-1411; FU NHLBI NIH HHS [K23 HL68064] NR 18 TC 35 Z9 35 U1 0 U2 2 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 2007 VL 18 IS 11 BP 1178 EP 1183 DI 10.1111/j.1540-8167.2007.00945.x PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 221YU UT WOS:000250264100010 PM 17887979 ER PT J AU Dougherty, CM Pyper, GP Au, DH Levy, WC Sullivan, MD AF Dougherty, Cynthia M. Pyper, Gail P. Au, David H. Levy, Wayne C. Sullivan, Mark D. TI Drifting in a shrinking future - Living with advanced heart failure SO JOURNAL OF CARDIOVASCULAR NURSING LA English DT Article DE congestive heart failure; palliative care; quality of life; qualitative research; shared decision making ID HEALTH-PROFESSIONALS; PALLIATIVE CARE; LIFE; CANCER; END; PREFERENCES; SKILLS AB Background: Patients with advanced heart failure (HF) have an uncertain prognosis and low rates of advance care planning and hospice use. The purpose of this study was to describe how patients view and plan for their future. Methods: Twenty-four (IN = 24) patients took part in a semistructured interview in which they were asked to describe their experiences in living with heart disease and their understanding and planning for their future. Interviews were transcribed and analyzed using the constant comparative method to generate a grounded theory. Results: The core category, "Living with HF," encompassed the subcategories of "My Experience of HF," "Help with HF," and "My Future with HF." This article reports on "My Future with HF." Patients wanted to discuss how HF affected their future with their providers, but initiation of these discussions was difficult and the absence of discussion led to frustration. Patients did not find specific life expectancy estimates helpful in coping or planning their future care. Conclusions: Patients with advanced HF do not plan well for end-of-life care and tend to drift along while vaguely hoping for the best. End-of-life care in advanced HF should address difficulties in decision making and provider communication. C1 Univ Washington, Sch Nursing, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Seattle, WA USA. Univ Washington, Sch Med, Seattle, WA 98195 USA. RP Dougherty, CM (reprint author), Univ Washington, Sch Nursing, Box 357266,1959 NE Pacific St,Room T608D, Seattle, WA 98195 USA. EM cindyd@u.washington.edu NR 22 TC 13 Z9 13 U1 1 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0889-4655 J9 J CARDIOVASC NURS JI J. Cardiovasc. Nurs. PD NOV-DEC PY 2007 VL 22 IS 6 BP 480 EP 487 PG 8 WC Cardiac & Cardiovascular Systems; Nursing SC Cardiovascular System & Cardiology; Nursing GA 230BK UT WOS:000250850100016 PM 18090189 ER PT J AU Kazanecki, CC Kowalski, AJ Ding, T Rittling, SR Denhardt, DT AF Kazanecki, Christian C. Kowalski, Aaron J. Ding, Tony Rittling, Susan R. Denhardt, David T. TI Characterization of anti-osteopontin monoclonal antibodies: Binding sensitivity to post-translational modifications SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE gene fragment display; phage display; epitope mapping; T7 phage; phosphorylation; cell adhesion; protein G ID O-GLYCOSYLATION SITES; IN-VITRO; OSTEOCLAST ADHESION; PHAGE DISPLAY; CELLS; PHOSPHORYLATION; IDENTIFICATION; PROTEINS; EPITOPES; CHEMOTAXIS AB Osteopontin (OPN) is primarily a secreted phosphoglycoprotein found in a variety of tissues and body fluids. It has a wide range of reported functions, many of which are affected by the degree of post-translational modification (PTM) of the protein. These PTMs include phosphorylation, glycosylation, and cross-linking by transglutaminase. Here we describe the generation of unique monoclonal antibodies raised against recombinant OPN utilizing the OPN knockout mouse. The antibodies exhibit differential binding to OPN produced by different cell lines from the same species, as well to the multiple OPN forms in human urine. Most of the antibodies generated are able to recognize OPN produced by ras-transformed mouse fibroblasts, however only one antibody recognizes the more phosphorylated protein produced by the differentiating pre-osteoblast murine cell line MC3T3E1. Using a novel biopanning procedure combining T7 phage gene fragment display and protein G precipitation, we have epitope-mapped these antibodies. Several of the antibodies bind to regions of the OPN molecule that are phosphorylated, and one binds the region of OPN that is glycosylated. Using phosphorylated and non-phosphorylated peptides, we show that the binding of two antibodies to the C-terminal end of OPN is inhibited by phosphorylation of this region. In addition, these two antibodies are able to inhibit cell adhesion to recombinant and weakly modified OPN. The antibodies described herein may prove useful in determining the presence of modifications at specific sites and for identifying structural forms of OPN. Also, the sensitivity of these antibodies to PTMs suggests that caution must be taken when choosing anti-OPN monoclonal antibodies to detect this highly modified protein. C1 Rutgers State Univ, Dept Cell Biol & Neurosci, Piscataway, NJ USA. Juvenile Diabetes Res Fdn, New York, NY USA. Forsyth Inst, Boston, MA USA. RP Denhardt, DT (reprint author), Nelson Labs, 604 Allison Rd, Piscataway, NJ 08854 USA. EM Denhardt@biology.rutgers.edu FU NIAMS NIH HHS [AR 44434]; NIDDK NIH HHS [DK 067685]; NIEHS NIH HHS [ES 06897] NR 38 TC 27 Z9 27 U1 1 U2 9 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 2007 VL 102 IS 4 BP 925 EP 935 DI 10.1002/jcb.21487 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 227DO UT WOS:000250637600013 PM 17786932 ER PT J AU Bermpohl, D You, Z Lo, EH Kim, HH Whalen, MJ AF Bermpohl, Daniela You, Zerong Lo, Eng H. Kim, Hyung-Hwan Whalen, Michael J. TI TNF alpha and Fas mediate tissue damage and functional outcome after traumatic brain injury in mice SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE brain trauma; genetics; knockout; neuroprotection; Fas; immature ID NECROSIS-FACTOR-ALPHA; SPINAL-CORD-INJURY; NERVOUS-SYSTEM; DEFICIENT MICE; UP-REGULATION; MOUSE-BRAIN; CELL-DEATH; LIGAND; RAT; NEUTRALIZATION AB Tumor necrosis factor-alpha (TNF alpha) and Fas are induced after traumatic brain injury (TBI); however, their functional roles are incompletely understood. Using controlled cortical impact (CCI) and mice deficient in TNF alpha, Fas, or both (TNF alpha/ Fas -/-), we hypothesized that TNF alpha and Fas receptor mediate secondary TBI in a redundant manner. Compared with wild type (WT), TNF alpha/ Fas -/- mice had improved motor performance from 1 to 4 days (P < 0.05), improved spatial memory acquisition at 8 to 14 days (P < 0.05), and decreased brain lesion size at 2 and 6 weeks after CCI (P < 0.05). Protection in TNF alpha/Fas -/- mice from histopathological and motor deficits was reversed by reconstitution with recombinant TNF alpha before CCI, and TNF alpha -/- mice administered anti- Fas ligand antibodies had improved spatial memory acquisition versus similarly treated WT mice ( P < 0.05). Tumor necrosis factor- alpha/Fas -/- mice had decreased the numbers of cortical cells with plasmalemma damage at 6h ( P< 0.05 versus WT), and reduced matrix metalloproteinase- 9 activity in injured brain at 48 and 72 h after CCI. In immature mice subjected to CCI, genetic inhibition of TNF alpha and Fas conferred beneficial effects on histopathology and spatial memory acquisition in adulthood (both P < 0.05 versus WT), suggesting that the beneficial effects of TNF alpha/ Fas inhibition may be permanent. The data suggest that redundant signaling pathways initiated by TNF alpha and Fas play pivotal roles in the pathogenesis of TBI, and that biochemical mechanisms downstream of TNF alpha/ Fas may be novel therapeutic targets to limit neurological sequelae in children and adults with severe TBI. C1 Massachusetts Gen Hosp, Dept Pediat Crit Care Med, Ctr Neurosci, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA USA. Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA USA. Massachusetts Gen Hosp, Dept Pediat, Charlestown, MA USA. Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA. Brigham & Womens Hosp, Vasc Med Res Unit, Cambridge, MA USA. RP Whalen, MJ (reprint author), Massachusetts Gen Hosp, Dept Pediat Crit Care Med, Ctr Neurosci, 149 13th St, Charlestown, MA 02129 USA. EM MWhalen@Partners.org FU NINDS NIH HHS [R01 NS40529, R01 NS47447, R01 NS48422] NR 39 TC 57 Z9 62 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD NOV PY 2007 VL 27 IS 11 BP 1806 EP 1818 DI 10.1038/sj.jcbfm.9600487 PG 13 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 222ZP UT WOS:000250338700004 PM 17406655 ER PT J AU Spencer, TJ Kratochvil, CJ Sangal, RB Saylor, KE Bailey, CE Dunn, DW Geller, DA Casat, CD Lipetz, RS Jain, R Newcorn, JH Ruff, DD Feldman, PD Furr, AJ Allen, AJ AF Spencer, Thomas J. Kratochvil, Christopher J. Sangal, R. Bart Saylor, Keith E. Bailey, Charles E. Dunn, David W. Geller, Daniel A. Casat, Charles D. Lipetz, Robert S. Jain, Rakesh Newcorn, Jeffrey H. Ruff, Dustin D. Feldman, Peter D. Furr, Amanda J. Allen, Albert J. TI Effects of atomoxetine on growth in children with attention-deficit/hyperactivity disorder following up to five years of treatment SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article ID HYPERACTIVE-CHILDREN; ADHD; METHYLPHENIDATE; WEIGHT; HEIGHT; AMPHETAMINE; ADOLESCENTS; PREDICTORS; MEDICATION; OBESITY AB Objective: To examine the effects on growth of long-term pharmacological treatment for attention-deficit/ hyperactivity disorder (ADHD), we present findings from an ongoing 5-year study of the efficacy and safety of treatment with atomoxetine. Methods: North American patients, 6-17 years old at study entry (N = 1,312) and with Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) ADHD, were studied under open-label atomoxetine treatment. Sixty-one were studied up to 5 years. Results: After 1 month's treatment, patients weighed less than expected from their starting percentiles relative to population norms, with a maximum shortfall at 15 months and a return to expected weight by 36 months. Patients were slightly shorter than expected after 12 months, reaching a maximum shortfall at 18 months and returning to expected height by 24 months. Patients in the top quartile for body mass index (BMI) or weight at baseline, and those in the third quartile for height, showed 5-year decreases from expected values. Those below median height at baseline showed increases relative to expected values. Conclusions: These interim results indicate that continuous atomoxetine treatment for up to 5 years has little or no long-term effect on juvenile growth and final stature for most patients, although persistent decreases from expected may occur in some patients who are larger than average before treatment. C1 [Spencer, Thomas J.; Geller, Daniel A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Psychopharmacol Clin, Boston, MA 02114 USA. [Kratochvil, Christopher J.] Univ Nebraska Med Ctr, Omaha, NE USA. [Sangal, R. Bart] Attent Disorders Inst, Troy, MI USA. [Saylor, Keith E.] Neurosci Inc, Herndon, VA USA. [Bailey, Charles E.] Psychiat Inst Florida, Clin Neurosci Solut, Orlando, FL USA. [Dunn, David W.; Furr, Amanda J.] Indiana Univ, Sch Med, Indianapolis, IN 46204 USA. [Bailey, Charles E.] Carolinas HealthCare Syst, Behav Hlth Ctr, Charlotte, NC USA. [Lipetz, Robert S.] Encompass Clin Res, Spring Valley, CA USA. [Jain, Rakesh] RD Clin Res Inc, Lake Jackson, TX USA. [Newcorn, Jeffrey H.] Mt Sinai Med Ctr, New York, NY 10029 USA. [Ruff, Dustin D.; Feldman, Peter D.; Allen, Albert J.] Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA. RP Spencer, TJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Psychopharmacol Clin, 55 Fruit St, Boston, MA 02114 USA. EM spencer@helix.mgh.harvard.edu OI Newcorn, Jeffrey /0000-0001-8993-9337 NR 37 TC 30 Z9 31 U1 2 U2 5 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD NOV PY 2007 VL 17 IS 5 BP 689 EP 699 DI 10.1089/cap.2006.0100 PG 11 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 256QT UT WOS:000252745400013 PM 17979588 ER PT J AU Magnee, MJCM de Gelder, B van Engeland, H Kemner, C AF Magnee, Maurice J. C. M. de Gelder, Beatrice van Engeland, Herman Kemner, Chantal TI Facial electromyographic responses to emotional information from faces and voices in individuals with pervasive developmental disorder SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY LA English DT Article DE autism; emotional processing; facial expressions; voice prosody; electromyography (EMG); multisensory perception ID YOUNG AUTISTIC-CHILDREN; NEURAL MECHANISMS; BRAIN RESPONSES; SOCIAL-BEHAVIOR; EXPRESSIONS; RECOGNITION; AMYGDALA; PEOPLE; PERCEPTION; IMITATION AB Background: Despite extensive research, it is still debated whether impairments in social skills of individuals with pervasive developmental disorder (PDD) are related to specific deficits in the early processing of emotional information. We aimed to test both automatic processing of facial affect as well as the integration of auditory and visual emotion cues in individuals with PDD. Methods: In a group of high-functioning adult individuals with PDD and an age- and IQ-matched control group, we measured facial electromyography (EMG) following presentation of visual emotion stimuli (facial expressions) as well as the presentation of audiovisual emotion pairs (faces plus voices). This emotionally driven EMG activity is considered to be a direct correlate of automatic affect processing that is not under intentional control. Results: Our data clearly indicate that among individuals with PDD facial EMG activity is heightened in response to happy and fearful faces, and intact in response to audiovisual affective information. Conclusions: This study provides evidence for enhanced sensitivity to facial cues at the level of reflex-like emotional responses in individuals with PDD. Furthermore, the findings argue against impairments in crossmodal affect processing at this level of perception. However, given how little comparative work has been done in the area of multisensory perception, there is certainly need for further exploration. C1 Univ Med Ctr Utrecht, Dept Child & Adolescent Psychiat, Rudolf Magnus Inst Neurosci, NL-3584 CX Utrecht, Netherlands. Tilburg Univ, Lab Cognit & Affect Neurosci, Tilburg, Netherlands. Maastricht Univ, Fac Psychol, Sect Biol Dev Psychol, Maastricht, Netherlands. Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Magnee, MJCM (reprint author), Univ Med Ctr Utrecht, Dept Child & Adolescent Psychiat, Rudolf Magnus Inst Neurosci, B01-201,Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands. EM M.J.C.M.Magnee@umcutrecht.nl NR 43 TC 34 Z9 37 U1 2 U2 17 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0021-9630 J9 J CHILD PSYCHOL PSYC JI J. Child Psychol. Psychiatry PD NOV PY 2007 VL 48 IS 11 BP 1122 EP 1130 DI 10.1111/j.1469-7610.2007.01779.x PG 9 WC Psychology, Developmental; Psychiatry; Psychology SC Psychology; Psychiatry GA 233HO UT WOS:000251082200010 PM 17995488 ER PT J AU Brambilla, DJ O'Donnell, AB Matsumoto, AM McKinlay, JB AF Brambilla, Donald J. O'Donnell, Amy B. Matsumoto, Alvin M. McKinlay, John B. TI Lack of seasonal variation in serum sex hormone levels in middle-aged to older men in the Boston area SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID FOLLICLE-STIMULATING-HORMONE; TO-HIP RATIO; LUTEINIZING-HORMONE; TESTOSTERONE LEVELS; PLASMA TESTOSTERONE; CIRCANNUAL RHYTHMS; CIRCADIAN-RHYTHMS; BINDING GLOBULIN; CORTISOL; MALES AB Context: Previous studies of seasonal variation of testosterone and other hormones in men have produced mixed results regarding the number and timing of peaks and nadirs and whether hormones vary seasonally at all. Wide variation in study designs, sample sizes, analytical methods, and characteristics of the study populations may account for the heterogeneity of results. Objective: The objective of the study was to determine whether serum total, free, and bioavailable testosterone, dihydrotestosterone, SHBG, LH, dehydroepiandrosterone, dehydroepiandrosterone sulfate, estrone, estradiol, and cortisol vary seasonally in men. Design: Two blood samples were drawn 1-3 d apart at study entry and again 3 and 6 months later ( maximum six samples per subject). Hormone levels 1-3 d apart were averaged to reduce short-term intrasubject variation. Setting: The study population consisted of a community-dwelling population ( Boston, MA). Study Participants: One hundred thirty-four men 30-79 yr old were randomly selected from the respondents to the Boston Area Community Health Survey. One hundred twenty-one men who completed all six visits were included in the analysis. Main Outcome Measures: In a repeated-measures analysis, 3-month change in hormone levels, measured twice per subject, and in a sinusoidal nonlinear regression with random subject effects, average hormone level in samples 1-3 d apart were measured. Results: Aside from cortisol, no evidence of seasonal variation in hormone levels was found. The amplitude of seasonal variation was much smaller than total intraindividual variation for all hormones considered. Conclusions: Seasonal variation is likely an unimportant source of variation clinically and in epidemiological studies of hormone levels. C1 New England Res Inst, Watertown, MA 02472 USA. Univ Washington, Sch Med, Seattle, WA 98108 USA. Univ Washington, Ctr Clin, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. RP Brambilla, DJ (reprint author), New England Res Inst, 9 Galen St, Watertown, MA 02472 USA. EM dbrambilla@neriscience.com RI Perez , Claudio Alejandro/F-8310-2010 OI Perez , Claudio Alejandro/0000-0001-9688-184X FU NIA NIH HHS [AG23027] NR 35 TC 19 Z9 19 U1 0 U2 2 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 2007 VL 92 IS 11 BP 4224 EP 4229 DI 10.1210/jc.2007-1303 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 228WR UT WOS:000250763800023 PM 17684044 ER PT J AU Yialamas, MA Dwyer, AA Hanley, E Lee, H Pitteloud, N Hayes, FJ AF Yialamas, Maria A. Dwyer, Andrew A. Hanley, Erin Lee, Hang Pitteloud, Nelly Hayes, Frances J. TI Acute sex steroid withdrawal reduces insulin sensitivity in healthy men with idiopathic hypogonadotropic hypogonadism SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID HORMONE-BINDING GLOBULIN; C-REACTIVE PROTEIN; ANDROGEN-DEPRIVATION THERAPY; DEPENDENT DIABETES-MELLITUS; NECROSIS-FACTOR-ALPHA; MIDDLE-AGED MEN; PROSTATE-CANCER; CARDIOVASCULAR-DISEASE; AROMATASE DEFICIENCY; METABOLIC SYNDROME AB Context: Evidence suggests that testosterone ( T) influences insulin sensitivity in men. The mechanism of this effect is unclear but is thought to involve changes in body composition. Objective: The aim of this study was to determine whether acute sex steroid withdrawal decreases insulin sensitivity in young, healthy men with idiopathic hypogonadotropic hypogonadism ( IHH). Design: This was a 2-wk prospective study. Setting: The study was conducted at a General Clinical Research Center. Patients: Twelve men with IHH ( age 40.8 +/- 2.8 yr) were studied: 1) on hormone replacement with normal T levels and 2) 2 wk after discontinuing therapy. Main Outcome Measures: Each evaluation comprised a 75-g oral glucose tolerance test with assessment of insulin sensitivity ( fasting insulin levels, homeostatic model assessment for insulin resistance, and Matsuda insulin sensitivity index) and insulin secretion ( corrected insulin response). Serum cortisol, leptin, adiponectin, free fatty acids, IL-6, C-reactive protein, and TNF-alpha levels were also measured. Results: Body mass index was unchanged ( 27.1 +/- 1.1 to 27.2 +/- 1.1 kg/m(2)). Serum T levels decreased from 529 +/- 65 to 28 +/- 8 ng/dl ( P < 0.00005). Fasting insulin levels increased from 4.9 +/- 0.7 to 6.2 +/- 0.6 mu U/ml ( P = 0.005), homeostatic model assessment of insulin resistance increased from 1.07 +/- 0.2 to 1.4 +/- 1.01 ( P < 0.005), and insulin sensitivity index decreased from 11.0 +/- 2.3 to 7.5 +/- 0.7 ( P < 0.05). There was a trend for fasting glucose levels to increase, 86.7 +/- 1.3 to 90.8 +/- 1.7 mg/dl ( P = 0.09). IL-6 levels increased from 1.2 +/- 0.2 to 2.4 +/- 0.5 pg/ml ( P < 0.01), whereas TNF-alpha levels decreased from 1.0 +/- 0.1 to 0.6 +/- 0.1 pg/ml ( P < 0.05). No other significant changes were observed. Conclusions: 1) Acute sex steroid withdrawal reduces insulin sensitivity in young healthy IHH men. 2) The acuity of the hypogonadism and absence of changes in body mass index or leptin levels suggest that sex steroids modulate insulin sensitivity in the absence of apparent or detectable changes in body composition. C1 Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Biostat, Boston, MA 02114 USA. Massachusetts Gen Hosp, Gen Clin Res Ctr, Boston, MA 02114 USA. RP Hanley, E (reprint author), Massachusetts Gen Hosp, Dept Med, Reprod Endocrine Unit, Bartleet Hall Extens 511, Boston, MA 02114 USA. EM fhayes@partners.org RI Dwyer, Andrew/D-8099-2012; PITTELOUD, Nelly/K-2709-2014 OI Dwyer, Andrew/0000-0002-7023-6794; FU NCRR NIH HHS [M01-RR-01066]; NIDDK NIH HHS [R03 DK064276 A 01] NR 62 TC 113 Z9 122 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 2007 VL 92 IS 11 BP 4254 EP 4259 DI 10.1210/jc.2007-0454 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 228WR UT WOS:000250763800028 PM 17726076 ER PT J AU Brugge, WR AF Brugge, William R. TI Optimizing methods for the diagnosis of pancreatic cancer SO JOURNAL OF CLINICAL GASTROENTEROLOGY LA English DT Editorial Material ID EUS-GUIDED FNA; MASSES C1 Massachusetts Gen Hosp, GI Unit Blake 4, Boston, MA 02114 USA. RP Brugge, WR (reprint author), Massachusetts Gen Hosp, GI Unit Blake 4, Boston, MA 02114 USA. EM wbrugge@partners.org NR 9 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0192-0790 J9 J CLIN GASTROENTEROL JI J. Clin. Gastroenterol. PD NOV-DEC PY 2007 VL 41 IS 10 BP 869 EP 870 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 228XF UT WOS:000250765200001 PM 18090153 ER PT J AU Abreu, MT Plevy, S Sands, BE Weinstein, R AF Abreu, Maria T. Plevy, Scott Sands, Bruce E. Weinstein, Robert TI Selective leukocyte apheresis for the treatment of inflammatory bowel disease SO JOURNAL OF CLINICAL GASTROENTEROLOGY LA English DT Review DE selective leukocyte apheresis; inflammatory bowel disease; ulcerative colitis; Crohn's disease ID ACTIVE ULCERATIVE-COLITIS; RANDOMIZED CONTROLLED TRIAL; MONOCYTE ADSORPTION APHERESIS; REFRACTORY CROHNS-DISEASE; LOW-DENSITY-LIPOPROTEIN; LYMPHOCYTE-T APHERESIS; STEROID-NAIVE PATIENTS; PLASMA-EXCHANGE; LEUKOCYTAPHERESIS THERAPY; DOUBLE-BLIND AB The etiology of inflammatory bowel disease (IBD) is not completely understood, thus current therapies have been empirical and directed at treating symptoms rather than addressing the cause. In IBD, the overexpression of proinflammatory cytokines, such as tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6, leads to a persistent intestinal inflammatory response that damages the intestinal mucosa. Recent advances in pharmacologic therapies that target specific cytokines, chemokines, and adhesion molecules have proved successful in alleviating symptoms for some patients. There are 2 selective adsorption apheresis devices that remove leukocytes from whole blood, which are currently available in Japan and Europe-the Cellsorba leukocytapheresis column and the Adacolumn adsorptive extracorporeal granulocyte/monocyte apheresis device. The purported mechanisms of action of these devices have been extensively reviewed and are believed to exert an immunomodulatory and/or anti-inflammatory effect on patients with systemic inflammatory disease. The clinical trials presented here indicate that selective leukocyte apheresis effectively removes activated granulocytes and monocytes/ macrophages from peripheral blood while maintaining an excellent safety profile. Despite these findings, large controlled trials of selective leukocyte apheresis in the treatment of IBD are needed to determine the true efficacy of this approach. C1 Univ Massachusetts, Sch Med, Massachusetts Gen Hosp, Div Transfus Med, Worcester, MA 01655 USA. Ctr Inflammatory Bowel Dis, New York, NY USA. Mt Sinai Sch Med, New York, NY USA. Univ N Carolina, Sch Med, Div Gastroenterol & Hepatol, Chapel Hill, NC USA. Harvard Univ, Sch Med, Cambridge, MA 02138 USA. Massachusetts Gen Hosp, MGH Crohns & Colitis Ctr, Boston, MA 02114 USA. UMass Mem Med Ctr, Div Transfus Med, Worcester, MA USA. RP Weinstein, R (reprint author), Univ Massachusetts, Sch Med, Massachusetts Gen Hosp, Div Transfus Med, 55 Lake Ave N, Worcester, MA 01655 USA. EM WeinsteR@ummhc.org NR 93 TC 20 Z9 20 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0192-0790 J9 J CLIN GASTROENTEROL JI J. Clin. Gastroenterol. PD NOV-DEC PY 2007 VL 41 IS 10 BP 874 EP 888 PG 15 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 228XF UT WOS:000250765200003 PM 18090155 ER PT J AU Shaib, YH Davila, JA Henderson, L McGlynn, KA El-Serag, HB AF Shaib, Yasser H. Davila, Jessica A. Henderson, Louise McGlynn, Katherine A. El-Serag, Hashem B. TI Endoscopic and surgical therapy for intrahepatic Cholangiocarcinoma in the united states - A population-based study SO JOURNAL OF CLINICAL GASTROENTEROLOGY LA English DT Article DE intrahepatic cholangiocarcinoma; outcomes AB Background: Intrahepatic cholangiocarcinoma (W-C) is a highly fatal disease with limited therapeutic options. The determinants, trends, and outcomes of different therapies for ICC are largely unknown in the United States. Methods: Using data from the Surveillance, Epidemiology, and End-Results-(SEER) Medicare database, we compared ICC patients receiving different therapies between 1992 and 1999. Univariate and multivariate analyses were performed and adjusted odds ratios (AORs) were calculated. Hazard ratios were calculated for the survival analysis. Results: Eight hundred sixty-two cases were included. The mean age at diagnosis was 77.9 years (SD = 7. 1). Only 6.3 % received surgical resection, 65.5% received palliative interventions (16.1 % surgical, 44.0% endoscopic), 24.4% received only chemo or radiation therapy whereas 3.8% did not receive any treatment. The median survival was 708 days [95% confidence interval (CI): 458-945] for surgical resection, 227 days (95% CI: 182-294) for surgical palliation, and 123 days (95% CI: 108-148) for endoscopic palliation. Patients receiving surgical resection were younger (AOR = 5.6, 95% CI: 2.9-11. 1), more likely to be diagnosed later in the study period (AOR 2.2, 95% CI: 1.1-4.2), and had better mortality (hazard ratio 0.3, 95% CI: 0.2-0.4). Patients receiving surgical palliation were younger (AOR = 1.6, 95% CI: 1.1-2.3), more likely to be diagnosed in the early time period (AOR = 1.5, 95% CI: 1.1-2.2), and had similar mortality to those receiving endoscopic palliation. Conclusions: Only a minority of patients with ICC receives potentially curative therapy. Young age is the strongest predictor of receiving potentially curative treatment. Older patients and those diagnosed in recent time periods are more likely to receive endoscopic palliation. Surgical resection was associated with improved survival. There was no difference in survival between surgical and endoscopic palliation. C1 Baylor Coll Med, Sect Hlth Serv Res, Houston Vet Affairs Med Ctr, NIH,DHHS, Bethesda, MD USA. Baylor Coll Med, Gastroenterol Sect, Houston Vet Affairs Med Ctr, Bethesda, MD USA. NCI, NIH, DHHS, Bethesda, MD 20892 USA. RP Shaib, YH (reprint author), Baylor Coll Med, Sect Hlth Serv Res, Houston Vet Affairs Med Ctr, NIH,DHHS, Bethesda, MD USA. EM yshaib@bcm.tmc.edu NR 17 TC 22 Z9 23 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0192-0790 J9 J CLIN GASTROENTEROL JI J. Clin. Gastroenterol. PD NOV-DEC PY 2007 VL 41 IS 10 BP 911 EP 917 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 228XF UT WOS:000250765200008 PM 18090160 ER PT J AU Polyak, K AF Polyak, Kornelia TI Breast cancer: origins and evolution SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Review ID MAMMARY STEM-CELLS; ADULT HUMAN BREAST; TUMOR-ASSOCIATED MACROPHAGES; EPITHELIAL PROGENITOR CELLS; GENOME-WIDE ASSOCIATION; ESTROGEN-RECEPTOR-ALPHA; TEMPLATE DNA STRANDS; CARCINOMA IN-SITU; STEM/PROGENITOR CELLS; MOLECULAR PORTRAITS AB Breast cancer is not a single disease, but rather is composed of distinct subtypes assosiated with different clinical outcomes. understanding this heterogeneity is key for the development of targeted cancer-preventative and -therapeutic interventions. Current models explaining inter- and intr- tumoral diversity are the cancer stem cell and the clonal evolution hypothesis. Although tumor initiation and progression are predominantly driven by acquired genetic alterations, recent data implicate a role for microenvironmental and epigenetic changes as well. Comprehensive unbiased studies of tumors and patient populations have significantly advanced our molecular understanding of breast cancer, but translating these findings into clinical practice remains a challenge. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, 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 FU NCI NIH HHS [CA89393, CA94074, P50 CA089393, R01 CA116235, R01 CA094074, CA116235] NR 115 TC 203 Z9 210 U1 1 U2 24 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD NOV PY 2007 VL 117 IS 11 BP 3155 EP 3163 DI 10.1172/JCI33295 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 227RR UT WOS:000250676000004 PM 17975657 ER PT J AU Li, J Sejas, DP Zhang, XL Qiu, YH Nattamai, KJ Rani, R Rathbun, KR Geiger, H Williams, DA Bagby, GC Pang, QS AF Li, June Sejas, Daniel P. Zhang, Xiaoling Qiu, Yuhui Nattamai, Kalpana J. Rani, Reena Rathbun, Keaney R. Geiger, Hartmut Williams, David A. Bagby, Grover C. Pang, Qishen TI TNF-alpha induces leukemic clonal evolution ex vivo in Fanconi anemia group C murine stem cells SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID NECROSIS-FACTOR-ALPHA; WILD-TYPE CELLS; HEMATOPOIETIC-CELLS; DNA-DAMAGE; IFN-GAMMA; REPOPULATING ABILITY; ENHANCES ENGRAFTMENT; INDUCED APOPTOSIS; NUCLEAR-COMPLEX; DEFICIENT CELLS AB The molecular pathogenesis of the myeloid leukemias that frequently occur in patients with Fanconi anemia (FA) is not well defined. Hematopoietic stem cells bearing inactivating mutations of FA complementation group C (FANCC) are genetically unstable and hypersensitive to apoptotic cytokine cues including IFN-gamma and TNF-alpha, but neoplastic stem cell clones that arise frequently in vivo are resistant to these cytokines. Reasoning that the combination of genetic instability and cytokine hypersensitivity might create an environment supporting the emergence of leukemic stem cells, we tested the leukemia-promoting effects of TNF-alpha in murine stem cells. TNF-alpha exposure initially profoundly inhibited the growth of Fancc(-/-) stem cells. However, longer-term exposure of these cells promoted the outgrowth of cytogenetically abnormal clones that, upon transplantation into congenic V/T mice, led to acute myelogenous leukemia. TNF-alpha. induced ROS-dependent genetic instability in Fancc(-/-) but not in WT cells. The leukemic clones were TNF-alpha resistant but retained their characteristic hypersensitivity to mitomycin C and exhibited high levels of chromosomal instability. Expression of FANCC cDNA in Fancc(-/-) stem cells protected them from TNF-alpha-induced clonal. evolution. We conclude that TNF-alpha exposure creates an environment in which somatically mutated preleukemic stem cell clones are selected and from which unaltered TNF-alpha-hypersensitive Fancc(-/-) stem cells are purged. C1 Childrens Hosp, Med Ctr, Div Expt Hematol, Cincinnati, OH 45229 USA. Oregon Hlth & Sci Univ, Sch Med, OHSU Canc Inst, Portland, OR 97201 USA. Univ Cincinnati, Coll Med, Dept Pediat, Cincinnati, OH USA. Portland VA Med Ctr, Portland, OR USA. RP Bagby, GC (reprint author), Childrens Hosp, Med Ctr, Div Expt Hematol, Cincinnati, OH 45229 USA. EM grover@ohsu.edu; qishen.pang@cchmc.org OI Bagby, Grover/0000-0001-6830-2046 FU NCI NIH HHS [R01 CA109641]; NCRR NIH HHS [M01 RR000334]; NHLBI NIH HHS [P01 HL048546, R01 HL076712] NR 58 TC 74 Z9 76 U1 0 U2 4 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD NOV PY 2007 VL 117 IS 11 BP 3283 EP 3295 DI 10.1172/JCI31772 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 227RR UT WOS:000250676000021 PM 17960249 ER PT J AU Yang, CL Zhu, XM Ellison, DH AF Yang, Chao-Ling Zhu, Xiaoman Ellison, David H. TI The thiazide-sensitive Na-Cl cotransporter is regulated by a WNK kinase signaling complex SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID PSEUDOHYPOALDOSTERONISM TYPE-II; BLOOD-PRESSURE; MOLECULAR PATHOGENESIS; POTASSIUM EXCRETION; SURFACE EXPRESSION; PROTEIN-KINASES; HYPERTENSION; SODIUM; TRANSPORT; TUBULE AB The pathogenesis of essential hypertension remains unknown, but thiazide diuretics are frequently recommended as first-fine treatment. Recently, familial hyperkalemic hypertension (FHHt) was shown to result from activation of the thiazide-sensitive Na-Cl cotransporter (NCC) by mutations in WNK4, although the mechanism for this effect remains unknown. WNK kinases are unique members of the human kinome, intimately involved in maintaining electrolyte balance across cell membranes and epithelia. Previous work showed that WNK1, WNK4, and a kidney-specific isoform of WNK1 interact to regulate NCC activity, suggesting that WNK kinases form a signaling complex. Here, we report that WNK3, another member of the WNK kinase family expressed by distal tubule cells, interacts with WNK4 and WNK1 to regulate NCC in both human kidney cells and Xenopus oocytes, further supporting the WNK signaling complex hypothesis. We demonstrate that physiological regulation of NCC in oocytes results from antagonism between WNK3 and WNK4 and that FHHt-causing WNK4 mutations exert a dominant-negative effect on wild-type (WT) WNK4 to mimic a state of WNK3 excess. The results provide a mechanistic explanation for the divergent effects of WT and FHHt-mutant WNK4 on NCC activity, and for the dominant nature of FHHt in humans and genetically modified mice. C1 Oregon Hlth & Sci Univ, Dept Med, Div Nephrol & Hypertens, Portland, OR 97239 USA. Portland VA Med Ctr, Portland, OR USA. Oregon Hlth & Sci Univ, Dept Physiol & Pharmacol, Portland, OR 97201 USA. Oregon Hlth & Sci Univ, Heart Res Ctr, Portland, OR 97201 USA. RP Yang, CL (reprint author), Oregon Hlth & Sci Univ, Dept Med, Div Nephrol & Hypertens, 3314 SW US Vet Hosp Rd, Portland, OR 97239 USA. OI Ellison, David/0000-0003-2915-265X FU NIDDK NIH HHS [DK51496, R01 DK051496] NR 41 TC 92 Z9 100 U1 0 U2 2 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD NOV PY 2007 VL 117 IS 11 BP 3403 EP 3411 DI 10.1172/JC132033 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 227RR UT WOS:000250676000032 PM 17975670 ER PT J AU Handschin, C Choi, CS Chin, S Kim, S Kawamori, D Kurpad, AJ Neubauer, N Hu, J Mootha, VK Kim, YB Kulkarni, RN Shulman, GI Spiegelman, BM AF Handschin, Christoph Choi, Cheol Soo Chin, Sherry Kim, Sheene Kawamori, Dan Kurpad, Amarnath J. Neubauer, Nicole Hu, Jiang Mootha, Vamsi K. Kim, Young-Bum Kulkarni, Rohit N. Shulman, Gerald I. Spiegelman, Bruce M. TI Abnormal glucose homeostasis in skeletal muscle-specific PGC-1 alpha knockout mice reveals skeletal muscle-pancreatic beta cell crosstalk SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID TRANSCRIPTIONAL COACTIVATOR PGC-1-ALPHA; INSULIN-RESISTANCE; OXIDATIVE-PHOSPHORYLATION; MITOCHONDRIAL DYSFUNCTION; ENERGY-METABOLISM; GENE-EXPRESSION; ERR-ALPHA; IN-VIVO; INTERLEUKIN-6; RECEPTOR AB The transcriptional coactivator PPAR gamma coactivator 1 alpha (PGC-1 alpha) is a strong activator of mitochondrial biogenesis and oxidative metabolism. While expression of PGC-1 alpha and many of its mitochondrial target genes are decreased in the skeletal muscle of patients with type 2 diabetes, no causal relationship between decreased PGC-1a expression and abnormal glucose metabolism has been established. To address this question, we generated skeletal muscle-specific PGC-1 alpha knockout mice (MKOs), which developed significantly impaired glucose tolerance but showed normal peripheral insulin sensitivity. Surprisingly, MKOs had expanded pancreatic beta cell mass, but markedly reduced plasma insulin levels, in both fed and fasted conditions. Muscle tissue from MKOs showed increased expression of several proinflammatory genes, and these mice also had elevated levels of the circulating IL-6. We further demonstrated that IL-6 treatment of isolated mouse islets suppressed glucose-stimulated insulin secretion. These data clearly illustrate a causal role for muscle PGC-1 alpha in maintenance of glucose homeostasis and highlight an unexpected cytokine-mediated crosstalk between skeletal muscle and pancreatic islets. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA. Univ Zurich, Inst Physiol, Zurich, Switzerland. Univ Zurich, Zurich Ctr Integrat Human Physiol, Zurich, Switzerland. Howard Hughes Med Inst, New Haven, CT 06510 USA. Yale Univ, Sch Med, Dept Internal Med, New Haven, CT USA. Yale Univ, Sch Med, Dept Cellular & Mol Physiol, New Haven, CT 06510 USA. Joslin Diabet Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA USA. MIT, Broad Inst, Cambridge, MA 02139 USA. Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA USA. Beth Israel Deaconess Med Ctr, Dept Med, Div Endocrinol Diabet & Metab, Boston, MA 02215 USA. RP Handschin, C (reprint author), Dana Farber Canc Inst, Smith Bldg,1 Jimmy Fund Way, Boston, MA 02115 USA. RI Handschin, Christoph/E-6886-2015 OI Handschin, Christoph/0000-0003-0603-1097 FU NIDDK NIH HHS [DK61562, DK54477, P30 DK040561, P30 DK040561-12, R01 DK-40936, R01 DK-67536, R01 DK040936, R01 DK054477, R01 DK061562, R01 DK067536, R56 DK054477, U24 DK-59635, U24 DK059635] NR 55 TC 186 Z9 196 U1 0 U2 12 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD NOV PY 2007 VL 117 IS 11 BP 3463 EP 3474 DI 10.1172/JC131785 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 227RR UT WOS:000250676000039 PM 17932564 ER PT J AU Le Gall, S Stamegna, P Walker, BD AF Le Gall, Sylvie Stamegna, Pamela Walker, Bruce D. TI Portable flanking sequences modulate CTL epitope processing SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; MHC CLASS-I; T-CELL RESPONSES; VIRAL PROTEIN EXPRESSION; ACUTE HIV-1 INFECTION; HEPATITIS-C VIRUS; TYPE-1 INFECTION; ENDOPLASMIC-RETICULUM; LYMPHOCYTE RESPONSES; ANTIGEN PRESENTATION AB Peptide presentation is critical for immune recognition of pathogen-infected cells by CD8(+) T lymphocytes. Although a limited number of immunodominant peptide epitopes are consistently observed in diseases such as HIV-1 infection, the relationship between inummodominance and antigen processing in humans is largely unknown. Here, we have demonstrated that endogenous processing and presentation of a human immunodominant HIV-1 epitope is more efficient than that of a subdominant epitope. Furthermore, we have shown that the regions flanking the immunodominant epitope constitute a portable motif that increases the production and antigenicity of otherwise subdominant epitopes. We used a novel in vitro degradation assay involving cytosolic extracts as well as endogenous intracellular processing assays to examine 2 well-characterized HIV-1 Gag overlapping epitopes presented by the same HLA class I allele, one of which is consistently immunodominant and the other subdominant in infected persons. The kinetics and products of degradation of HIV-1 Gag favored the production of peptides encompassing the immunodominant epitope and destruction of the subdominant one. Notably, cytosolic digestion experiments revealed flanking residues proximal to the immunodominant epitope that increased the production and antigenicity of otherwise subdominant epitopes. Furthermore, specific point mutations in these portable flanking sequences modulated the production and antigenicity of epitopes. Such portable epitope processing determinants provide what we believe is a novel approach to optimizing CTL responses elicited by vaccine vectors. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02129 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02129 USA. RP Le Gall, S (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr, 149 13th St, Boston, MA 02129 USA. FU NIAID NIH HHS [AI 060354, R01 AI028568, R21 AI060502, R21 AI060502-01A1, AI28568-16, AI060502-01A1, P30 AI060354, R21 AI060502-02, R37 AI028568] NR 82 TC 64 Z9 66 U1 0 U2 4 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD NOV PY 2007 VL 117 IS 11 BP 3563 EP 3575 DI 10.1172/JC132047 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 227RR UT WOS:000250676000048 PM 17975674 ER PT J AU Zeng, JS Sutton, DA Fothergill, AW Rinaldi, MG Harrak, MJ de Hoog, GS AF Zeng, J. S. Sutton, D. A. Fothergill, A. W. Rinaldi, M. G. Harrak, M. J. de Hoog, G. S. TI Spectrum of clinically relevant Exophiala species in the United States SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID WANGIELLA-DERMATITIDIS; CYSTIC-FIBROSIS; CEREBRAL PHEOHYPHOMYCOSIS; NUTRITIONAL PHYSIOLOGY; ANTIFUNGAL AGENTS; SPINIFERA CLADE; JEANSELMEI; FUNGEMIA; CHROMOBLASTOMYCOSIS; SUSCEPTIBILITIES AB Numerous members of the genus Exophiala are potential agents of human and animal mycoses. The majority of these infections are cutaneous and superficial, but also fatal systemic infections are known. We re-identified 188 clinical isolates from the United States, which had a preliminary morphological identification of Exophiala species, by sequencing internal transcribed spacer (ITS) region of the rRNA. Molecular identifications of the strains were as follows, in order of frequency: 55 E. dermatitidis (29.3%), 37 E. xenobiotica (19.7%), 35 E. oligosperma (18.6%), 13 E. lecanii-corni (6.9%), 12 E. phaeomuriformis (6.4%), 7 E. jeanselmei (3.7%), 7 E. bergeri (3.7%), 6 E. mesophila (3.2%), 5 E. spinifera (2.7%), 3 Exophiala sp. 1 (1.6%), 3 E. attenuata (1.6%), 3 Phialophora europaea (1.3%), 1 E. heteromorpha (0.5%), and 1 Exophiala sp. 2 (0.5%) strains. Exophiala strains were repeatedly isolated from deep infections (39.9%) involving lung, pleural fluid, sputum, digestive organs (stomach, intestines, bile), heart, brain, spleen, bone marrow, blood, dialysis fluid, lymph node, joint, breast, middle ear, throat, and intraocular tissues. About 38.3% of the Exophiala spp. strains were agents of cutaneous infections including skin, mucous membranes, nail, and corneal epithelium lesions. The other strains caused superficial infections (0.5%, including hair) or subcutaneous infection (12.0%, including paranasal sinusitis, mycetoma, and subcutaneous cyst). The systemic infections were preponderantly caused by E. dermatitidis, E. oligosperma, E. phaeomuriformis, E. xenobiotica, and E. lecanii-corni. Strains of E. bergeri, E. spinifera, E. jeanselmei, E. mesophila, and E. attenuata mainly induced cutaneous and subcutaneous infections. Since relatively few unknown ITS motifs were encountered, we suppose that the list of opportunistic Exophiala species in temperate climates is nearing completion, but a number of species still have to be described. C1 Cent Bur Schimmelcultures, NL-3508 AD Utrecht, Netherlands. Inst Biodivers & Ecosyst Dynam, Amsterdam, Netherlands. Huazhong Univ Sci & Technol, Tongji Med Coll, Dept Dermatol & Venerol, Union Hosp, Wuhan 430074, Hebei, Peoples R China. Univ Texas, Hlth Sci Ctr, Fungus Testing Lab, San Antonio, TX USA. Audie L Murphy Mem Vet Adm Med Ctr, S Texas Vet Hlth Care Syst, San Antonio, TX 78284 USA. RP de Hoog, GS (reprint author), Cent Bur Schimmelcultures, POB 85167, NL-3508 AD Utrecht, Netherlands. EM de.hoog@cbs.knaw.nl NR 40 TC 101 Z9 103 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD NOV PY 2007 VL 45 IS 11 BP 3713 EP 3720 DI 10.1128/JCM.02012-06 PG 8 WC Microbiology SC Microbiology GA 231FU UT WOS:000250932700035 PM 17596364 ER PT J AU Waber, DP Turek, J Catania, L Stevenson, K Robaey, P Romero, I Adams, H Alyman, C Jandet-Brunet, C Neuberg, DS Sallan, SE Silverman, LB AF Waber, Deborah P. Turek, Jennifer Catania, Lori Stevenson, Kristen Robaey, Philippe Romero, Ivonne Adams, Heather Alyman, Cheryl Jandet-Brunet, Christine Neuberg, Donna S. Sallan, Stephen E. Silverman, Lewis B. TI Neuropsychological outcomes from a Randomized trial of triple intrathecal chemotherapy compared with 18 gy cranial radiation as CNS treatment in acute lymphoblastic leukemia: Findings from dana-farber cancer institute ALL consortium protocol 95-01 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID LONG-TERM SURVIVORS; FOLLOW-UP; INTELLECTUAL FUNCTION; THERAPEUTIC-EFFICACY; CHILDHOOD LEUKEMIA; COGNITIVE SEQUELAE; YOUNG-CHILDREN; METHOTREXATE; IRRADIATION; NEUROTOXICITY AB Purpose We evaluated late neuropsychological toxicity in children treated for standard-risk acute lymphoblastic leukemia (ALL) who were randomly assigned to receive either cranial radiation therapy (CRT) with double intrathecal (IT) chemotherapy or intensive triple IT chemotherapy (no CRT) as CNS-directed therapy. Patients and Methods Between 1996 and 2000, 164 children with standard-risk ALL treated on Dana-Farber Cancer Institute Consortium Protocol 95-01 were randomly assigned to receive either 18 Gy CRT delivered in twice daily fractions (9 Gy) with double IT therapy (methotrexate and cytarabine) or intensive triple IT drug (methotrexate, cytarabine and hydrocortisone) without CRT. Neuropsychological testing was completed at a median 6 years postdiagnosis for 79 children (CRT, n = 39; triple IT, n = 40), all of whom were in continuous complete remission. Results Cognitive function for both groups was solidly in the average range, with no consistent group differences in basic cognitive skills. Children treated on the CRT plus double IT arm did, however, exhibit less fluent output and were less effective at modulating their behavior by parent report. Conclusion This randomized trial revealed only subtle differences 6 years after diagnosis between children who received CNS therapy as CRT plus double IT drug or as intensive triple IT drug. In most situations where comparable therapeutic efficacy can be achieved without CRT, it is preferable to do so. Where therapeutically necessary, however, CRT at lower doses may not add risk for significant neurotoxicity. C1 Childrens Hosp, Dept Psychiat, Div Psychol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Psychiat, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Dept Pediat, Cambridge, MA 02138 USA. Dana Farber Canc Inst, Childrens Hosp, Div Hematol & Oncol, Dept Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Comp Biol, Boston, MA 02115 USA. Univ Rochester, Med Ctr, Golisano Chidrens Hosp Strong, Dept Pediat, Rochester, NY 14642 USA. McMaster Univ, Div Pediat Hematol Oncol, Hamilton, ON, Canada. Hop St Justine, Div Hematol Oncol, Dept Pediat Hematol, Montreal, PQ, Canada. Hop St Justine, Div Hematol Oncol, Dept Oncol, Montreal, PQ, Canada. Ctr Mere Enfant, Dept Pediat Hematol Oncol, Quebec City, PQ, Canada. Interamer Univ, San German, PR USA. RP Waber, DP (reprint author), Childrens Hosp, Dept Psychiat, Div Psychol, 300 Longwood Ave, Boston, MA 02115 USA. EM deborah.waber@childrens.harvard.edu NR 37 TC 56 Z9 60 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV 1 PY 2007 VL 25 IS 31 BP 4914 EP 4921 DI 10.1200/JCO.2007.10.8464 PG 8 WC Oncology SC Oncology GA 233EV UT WOS:000251074100010 PM 17971588 ER PT J AU Goss, P Bondarenko, IN Manikhas, GN Pendergrass, KB Miller, WH Langecker, P Blanchett, D AF Goss, Paul Bondarenko, Igor N. Manikhas, Georgiy N. Pendergrass, Kelly B. Miller, Wilson H., Jr. Langecker, Peter Blanchett, Dennis TI Phase III, double-blind, controlled trial of atamestane plus Toremifene compared with letrozole in postmenopausal women with advanced receptor-positive breast cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID FIRST-LINE THERAPY; AROMATASE INHIBITORS; RANDOMIZED-TRIAL; 1ST-LINE THERAPY; TAMOXIFEN; ANASTROZOLE; SUPERIOR; EFFICACY; ESTROGEN; HYPERSENSITIVITY AB Purpose To compare time to progression (TTP) with a steroidal aromatase inhibitor (AI) atamestane (ATA) combined with toremifene (TOR; complete estrogen blockade) versus letrozole (LET) in receptor-positive advanced breast cancer (ABC). Patients and Methods Eligibility included postmenopausal receptor-positive ABC and adjuvant hormonal therapy completed more than 12 months prior to study entry. Participants received daily ATA 500 mg with TOR 60 mg (ATA + TOR), or letrozole 2.5 mg (LET). The primary end point was TTP, whereas secondary objectives included objective response (OR), overall survival (OS), and time to treatment failure (TTF). The study had 80% power to detect a 25% increase in TTP assuming a TTP of 9.4 months in the LET population. Results A total of 865 patients were randomly assigned (434 to ATA + TOR and 431 to LET) in 60 centers in the United States, Canada, Russia, and Ukraine. Baseline characteristics were balanced. Median TTP was identical in the two arms at 11.2 months (P = .92). Median TTF was similar at 9.24 months (ATA + TOR) versus 10.44 months (LET). The hazard ratios (LET/ATA + TOR) were 1.00 (95% CI, 0.92 to 1.08) for TTP, 0.99 ( 95% CI, 0.92 to 1.06) for TTF, and 0.98 (95% CI, 0.87 to 1.11) for OS. OR occurred in 30% of patients receiving ATA + TOR and in 36% of patients receiving LET (P < .1). Adverse events (AEs) were similar for patients receiving ATA + TOR versus LET, and serious AEs were 10% v 11%, respectively. Conclusion TTP for patients receiving ATA + TOR was identical to that for patients receiving LET, representing the first endocrine therapy comparable to LET in ABC. Unlike in the Anastrozole, Tamoxifen, and Combined trial, addition of an antiestrogen did not decrease efficacy of the AI. Future studies of AIs in combination with more effective selective estrogen receptor modulators or selective receptor downregulators is warranted. C1 Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Dnepropetrovsk State Med Acad, Dnepropetrovsk, Ukraine. Russian Fed, St Petersburg City Oncol Ctr, St Petersburg, Russia. Kansas City Canc Ctr, Kansas City, MO USA. McGill Univ, Montreal, PQ, Canada. Intarcia Pharmaceut Inc, Emeryville, CA USA. RP Goss, P (reprint author), Harvard Univ, Sch Med, 55 Fruit St,Lawrence House,LRH-302, Boston, MA 02114 USA. EM pgoss@partners.org OI Bondarenko, Igor/0000-0002-7071-2471 NR 21 TC 10 Z9 10 U1 3 U2 4 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV 1 PY 2007 VL 25 IS 31 BP 4961 EP 4966 DI 10.1200/JCO.2006.09.5455 PG 6 WC Oncology SC Oncology GA 233EV UT WOS:000251074100017 PM 17971594 ER PT J AU Singh, H Sethi, S Raber, M Petersen, LA AF Singh, Hardeep Sethi, Saurabh Raber, Martin Petersen, Laura A. TI Errors in cancer diagnosis: Current understanding and future directions SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID SCREENING MAMMOGRAPHY INTERPRETATION; POPULATION-BASED ANALYSIS; FALSE-NEGATIVE MAMMOGRAM; BARIUM ENEMA EXAMINATION; COLONOSCOPIC MISS RATES; CHEST X-RAYS; LUNG-CANCER; BREAST-CANCER; COLORECTAL-CANCER; CLINICAL DIAGNOSES AB Purpose Errors in cancer diagnosis are likely the most harmful and expensive types of diagnostic errors. We reviewed the literature to understand the prevalence, origins, and prevention of errors in cancer diagnosis, focusing on common cancers for which early diagnosis offers clear benefit (melanoma and cancers of the breast, colon, and lung). Methods We searched the Cochrane Library and PubMed from 1966 until April 2007 for publications that met our review criteria and manually searched references of key publications. Our search yielded 110 studies, of which nine were prospective studies and the remaining were retrospective studies. Results Errors in cancer diagnosis were not uncommon in autopsy studies and were associated with significant harm and expense in malpractice claims. Literature on prevalence was scant. For each type of cancer, we classified preventable errors according to their origins in patient-physician encounters in the clinic setting, diagnostic test or procedure performance, pathologic confirmation of diagnosis, follow-up of patient or test result, or patient-related delays. Conclusion The literature reflects advanced knowledge of contributory factors and prevention for diagnostic errors related to the performance of procedures and imaging tests and emerging understanding of pathology errors. However, prospective studies are few, as are studies of diagnostic errors arising from the clinical encounter and patient follow-up. Future research should examine further the system and cognitive problems that lead to the many contributory factors we identified, and address interdisciplinary interventions to prevent errors in cancer diagnosis. C1 Baylor Coll Med, Dept Med, Sect Hlth Serv Res, Houston, TX 77030 USA. Univ Texas, Sch Publ Hlth, Houston, TX USA. RP Singh, H (reprint author), VA Med Ctr 152, 2002 Holcombe Blvd, Houston, TX 77030 USA. EM hardeeps@bcm.tmc.edu FU NCI NIH HHS [K23CA125585] NR 164 TC 47 Z9 48 U1 0 U2 4 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD NOV 1 PY 2007 VL 25 IS 31 BP 5009 EP 5018 DI 10.1200/JCO.2007.13.2142 PG 10 WC Oncology SC Oncology GA 233EV UT WOS:000251074100024 PM 17971601 ER PT J AU Tanner, ACR Kent, R Kanasi, E Lu, SC Paster, BJ Sonis, ST Murray, LA Van Dyke, TE AF Tanner, Anne C. R. Kent, Ralph, Jr. Kanasi, Eleni Lu, Shulin C. Paster, Bruce J. Sonis, Steven T. Murray, Lora A. Van Dyke, Thomas E. TI Clinical characteristics and microbiota of progressing slight chronic periodontitis in adults SO JOURNAL OF CLINICAL PERIODONTOLOGY LA English DT Article DE DNA probes; gingivitis; microbiology; P. gingivalis; slight chronic periodontitis; T. forsythia ID DWELLING OLDER-ADULTS; HUMAN SUBGINGIVAL PLAQUE; ATTACHMENT LOSS; ACTINOBACILLUS-ACTINOMYCETEMCOMITANS; PORPHYROMONAS-GINGIVALIS; RISK INDICATORS; BACTEROIDES-FORSYTHUS; BACTERIAL DIVERSITY; TOPOGRAPHIC DISTRIBUTION; MINORITY POPULATIONS AB Aim: This study sought clinical and microbial risk indicators for progressing slight periodontitis. Material and Methods: One hundred and seventeen periodontally healthy or slight periodontitis adults (20-40 years) were monitored clinically at 6-month intervals followed by supragingival cleaning. Inter-proximal sites with > 1.5 mm increase in clinical attachment over 18 months were considered disease active. Subgingival plaque was analysed by 78 16S rDNA and 38 whole-genomic DNA probes and by PCR to Porphyromonas gingivalis and Tannerella forsythia. Characteristics were compared between active and inactive subjects. Results: Twenty-two subjects showed disease activity principally at molars. Mean baseline gingival and plaque indices, bleeding on probing, probing depth and clinical attachment level (CAL) were higher in active subjects. DNA probes detected species and not-yet-cultivated phylotypes from chronic periodontitis, although few species were associated with active subjects. By PCR P. gingivalis (p=0.007) and T. forsythia (p=0.075) were detected more frequently during monitoring in active subjects. Stepwise logistic analysis associated baseline levels of gingival index, clinical attachment and bleeding with subsequent clinical attachment loss. Conclusions: Gingivitis and CAL were significantly associated with progressing slight periodontitis in 20-40-year-old adults. Species associated with moderate and advanced chronic periodontitis were detected in slight periodontitis. C1 Forsyth Inst, Dept Mol Genet, Boston, MA 02115 USA. Forsyth Inst, Clin Res Ctr, Boston, MA 02115 USA. Forsyth Inst, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Oral Med & Oral Pathol, Boston, MA 02115 USA. Boston Univ, Sch Dent Med, Clin Res Ctr, Boston, MA 02215 USA. RP Tanner, ACR (reprint author), Forsyth Inst, Dept Mol Genet, 140 Fenway, Boston, MA 02115 USA. EM annetanner@forsyth.org FU NCRR NIH HHS [RR-00533, RR-01032]; NIDCR NIH HHS [DE-007151, DE-09513, DE-11443] NR 62 TC 24 Z9 27 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0303-6979 J9 J CLIN PERIODONTOL JI J. Clin. Periodontol. PD NOV PY 2007 VL 34 IS 11 BP 917 EP 930 DI 10.1111/j.1600-051X.2007.01126.x PG 14 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 220GM UT WOS:000250145200002 PM 17877747 ER PT J AU Moore, TA Buchanan, RW Buckley, PF Chiles, JA Conley, RR Crismon, ML Essock, SM Finnerty, M Marder, SR Miller, DD McEvoy, JP Robinson, DG Schooler, NR Shon, SP Stroup, IS Miller, AL AF Moore, Troy A. Buchanan, Robert W. Buckley, Peter F. Chiles, John A. Conley, Robert R. Crismon, M. Lynn Essock, Susan M. Finnerty, Molly Marder, Stephen R. Miller, Del D. McEvoy, Joseph P. Robinson, Delbert G. Schooler, Nina R. Shon, Steven P. Stroup, I. Scott Miller, Alexander L. TI The texas medication algorithm project antipsychotic algorithm for schizophrenia: 2006 update SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID ACTING INJECTABLE RISPERIDONE; TREATMENT-RESISTANT SCHIZOPHRENIA; NEW-GENERATION ANTIPSYCHOTICS; RANDOMIZED CONTROLLED-TRIAL; PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND; TARDIVE-DYSKINESIA; SCHIZOAFFECTIVE DISORDER; 2ND-GENERATION ANTIPSYCHOTICS; 1ST-EPISODE SCHIZOPHRENIA AB Background: A panel of academic psychiatrists and pharmacists, clinicians from the Texas public mental health system, advocates, and consumers met in June 2006 in Dallas, Tex., to review recent evidence in the pharmacologic treatment of schizophrenia. The goal of the consensus conference was to update and revise the Texas Medication Algorithm Project (TMAP) algorithm for schizophrenia used in the Texas Implementation of Medication Algorithms, a statewide quality assurance program for treatment of major psychiatric illness. Method: Four questions were identified via premeeting teleconferences. (1) Should antipsychotic treatment of first-episode schizophrenia be different from that of multiepisode schizophrenia? (2) In which algorithm stages should first-generation antipsychotics (FGAs) be an option? (3) How many antipsychotic trials should precede a clozapine trial? (4) What is the status of augmentation strategies for clozapine? Subgroups reviewed the evidence in each area and presented their findings at the conference. Results: The algorithm was updated to incorporate the following recommendations. (1) Persons with first-episode schizophrenia typically require lower antipsychotic doses and are more sensitive to side effects such as weight gain and extrapyramidal symptoms (group consensus). Second-generation antipsychotics (SGAs) are preferred for treatment of first-episode schizophrenia (majority opinion). (2) FGAs should be included in algorithm stages after first episode that include SGAs other than clozapine as options (group consensus). (3) The recommended number of trials of other antipsychotics that should precede a clozapine trial is 2, but earlier use of clozapine should be considered in the presence of persistent problems such as suicidality, comorbid violence, and substance abuse (group consensus). (4) Augmentation is reasonable for persons with inadequate response to clozapine, but published results on augmenting agents have not identified replicable positive results (group consensus). Conclusions: These recommendations are meant to provide a framework for clinical decision making, not to replace clinical judgment. As with any algorithm, treatment practices will evolve beyond the recommendations of this consensus conference as new evidence and additional medications become available. C1 Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. Univ Maryland, Sch Med, Maryland Psychiat Res Ctr, Baltimore, MD 21201 USA. Med Coll Georgia, Dept Psychiat, Augusta, GA 30912 USA. Univ Washington, Dept Psychiat, Sch Med, Seattle, WA 98195 USA. Univ Texas Austin, Coll Pharm, Austin, TX 78712 USA. New York State Psychiat Inst & Hosp, Dept Mental Hlth Serv & Policy Res, New York, NY 10032 USA. New York Off State Mental Hlth, New York, NY USA. W Los Angeles VA Hlth Care Ctr, Los Angeles, CA USA. Univ Iowa, Dept Psychiat, Carver Coll Med, Iowa City, IA 52242 USA. Duke Univ, Dept Psychiat & Behav Sci, Durham, NC USA. Zucker Hillside Hosp N Shore Long Isl Jewish Hlth, Dept Psychiat, Glen Oaks, NY USA. Feinstein Inst Med Res, Manhasset, NY USA. Albert Einstein Coll Med, Dept Psychiat & Behav Sci, Bronx, NY 10467 USA. Georgetown Univ, Sch Med, Dept Psychiat, Washington, DC USA. VISN5 MIRECC, Dept Vet Affairs, Washington, DC USA. Univ N Carolina, Dept Psychiat, Chapel Hill, NC 27515 USA. RP Moore, TA (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. EM mooret3@uthscsa.edu RI Stroup, Thomas/F-9188-2014 OI Stroup, Thomas/0000-0002-3123-0672 NR 78 TC 128 Z9 129 U1 4 U2 10 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD NOV PY 2007 VL 68 IS 11 BP 1751 EP 1762 PG 12 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 234QQ UT WOS:000251179200015 PM 18052569 ER PT J AU Shapiro, MD Neilan, TG Jassal, DS Samy, B Nasir, K Hoffmann, U Sarwar, A Butler, J Brady, TJ Cury, RC AF Shapiro, Michael D. Neilan, Tomas G. Jassal, Davinder S. Samy, Bharat Nasir, Khurram Hoffmann, Udo Sarwar, Ammar Butler, Javed Brady, Thomas J. Cury, Ricardo C. TI Multidetector computed tomography for the detection of left atrial appendage thrombus: A comparative study with transesophageal echocardiography SO JOURNAL OF COMPUTER ASSISTED TOMOGRAPHY LA English DT Article DE left atrial appendage; thrombus; multidetector computed tomography; transesophageal echocardiography ID 2-DIMENSIONAL ECHOCARDIOGRAPHY AB Objective: To determine the diagnostic performance of multidetector computed tomography (MDCT) for the detection of left atrial appendage (LAA) thrombus as compared with transesophageal echocardiography. Methods: Multidetector computed tomography was evaluated in 43 patients qualitatively for the presence or absence of a filling defect in the LAA and compared with transesophageal echocardiography. Additionally, a ratio of the mean computed tomographic attenuation in the LAA apex to the mean computed tomographic attenuation in the aortic root was used for quantitative evaluation. Results: A filling defect visualized in the LAA by MDCT corresponded to a sensitivity of 70% (7/10), a specificity of 82% (27/33), and a negative predictive value of 90% (27/30) for detection of LAA thrombus. When using quantitative parameters, MDCT demonstrated a sensitivity of 80% (8/10), a specificity of 73% (24/33), and a negative predictive value of 92% (24/26). Multidetector computed tomography was not able to differentiate LAA thrombus from spontaneous echo contrast by either visual evaluation or by quantitative parameters. Conclusions: Multidetector computed tomography remains limited for the detection of LAA thrombus. However, a subgroup of patients at very high risk for LAA thrombus may benefit from the high negative predictive value of cardiac MDCT. C1 [Shapiro, Michael D.; Samy, Bharat; Nasir, Khurram; Hoffmann, Udo; Sarwar, Ammar; Butler, Javed; Brady, Thomas J.; Cury, Ricardo C.] Harvard Med Sch, Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA. [Neilan, Tomas G.; Jassal, Davinder S.] Harvard Med Sch, Massachusetts Gen Hosp, Div Cardiol, Boston, MA USA. RP Cury, RC (reprint author), Massachusetts Gen Hosp, Dept Radiol, Suite 400, 165 Cambridge Str, Boston, MA 02114 USA. EM rcury@partners.org FU NHLBI NIH HHS [1T32 HL076136-02] NR 10 TC 32 Z9 34 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0363-8715 J9 J COMPUT ASSIST TOMO JI J. Comput. Assist. Tomogr. PD NOV-DEC PY 2007 VL 31 IS 6 BP 905 EP 909 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 239ZO UT WOS:000251557000013 PM 18043355 ER PT J AU Teughels, W Newman, MG Coucke, W Haffajee, AD Van der Mei, HC Haake, SK Schepers, E Cassiman, JJ Van Eldere, J van Steenberghe, D Quirynen, M AF Teughels, W. Newman, M. G. Coucke, W. Haffajee, A. D. Van Der Mei, H. C. Haake, S. Kinder Schepers, E. Cassiman, J.-J. Van Eldere, J. van Steenberghe, D. Quirynen, M. TI Guiding periodontal pocket recolonization: a proof of concept SO JOURNAL OF DENTAL RESEARCH LA English DT Article DE probiotics; periodontitis; therapy; microbial interference; replacement therapy; treatment ID INTERFERING ALPHA-STREPTOCOCCI; CARIOGENIC BACTERIA; ADULT PERIODONTITIS; CONTROLLED TRIAL; IMMUNE-RESPONSE; THERAPY; DISEASE; PLAQUE; FLORA; ACTINOMYCETEMCOMITANS AB The complexity of the periodontal microbiota resembles that of the gastro-intestinal tract, where infectious diseases are treatable via probiotics. In the oro-pharyngeal region, probiotic or replacement therapies have shown some benefit in the prevention of dental caries, otitis media, and pharyngitis, but their effectiveness in the treatment of periodontitis is unknown. Therefore, this study addressed the hypothesis that the application of selected beneficial bacteria, as an adjunct to scaling and root planing, would inhibit the periodontopathogen recolonization of periodontal pockets. Analysis of the data showed, in a beagle dog model, that when beneficial bacteria were applied in periodontal pockets adjunctively after root planing, subgingival recolonization of periodontopathogens was delayed and reduced, as was the degree of inflammation, at a clinically significant level. The study confirmed the hypothesis and provides a proof of concept for a guided pocket recolonization (GPR) approach in the treatment of periodontitis. C1 Catholic Univ Louvain, Res Grp Microbial Adhes, Dept Periodontol, B-3000 Louvain, Belgium. Univ Calif Los Angeles, Sch Dent, Los Angeles, CA 90024 USA. Forsyth Inst, Dept Periodont, Boston, MA USA. Univ Groningen, Dept Biomed Engn, NL-9713 AV Groningen, Netherlands. Catholic Univ Louvain, Biomat Res Cluster, B-3000 Louvain, Belgium. Catholic Univ Louvain, Dept Human Genet, B-3000 Louvain, Belgium. Catholic Univ Louvain, Ctr Mol Diagnost, B-3000 Louvain, Belgium. RP Teughels, W (reprint author), Catholic Univ Louvain, Res Grp Microbial Adhes, Dept Periodontol, Kapucijnenvoer 7, B-3000 Louvain, Belgium. EM Wim.Teughels@med.kuleuven.be RI Teughels, Wim/F-4337-2014 FU NIDCR NIH HHS [DE015360] NR 32 TC 39 Z9 42 U1 2 U2 10 PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 0022-0345 J9 J DENT RES JI J. Dent. Res. PD NOV PY 2007 VL 86 IS 11 BP 1078 EP 1082 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 223YX UT WOS:000250413200011 PM 17959900 ER PT J AU Ioannou, GN Bryson, CL Boyko, EJ AF Ioannou, George N. Bryson, Chris L. Boyko, Edward J. TI Prevalence and trends of insulin resistance, impaired fasting glucose, and diabetes SO JOURNAL OF DIABETES AND ITS COMPLICATIONS LA English DT Article ID US ADULTS; MELLITUS; RISK; DIAGNOSIS; OBESITY; HEALTH AB Objective: Our aim was to measure the prevalence and time trends of diabetes, impaired fasting glucose, and insulin resistance in the United States during the periods 1988-1994 and 1999-2002. Materials and methods: Data were derived from two nationally representative samples of the adult U.S. population collected as part of the National Health and Nutrition Examination Surveys of 1988-1994 (n=18,800) and 1999-2002 (n=10,283). We compared these two samples with respect to the following outcomes: previously diagnosed diabetes defined by self-report; undiagnosed diabetes defined as fasting plasma glucose >= 126 mg/dl; impaired fasting glucose defined as fasting plasma glucose 100-125 mg/dl; and insulin resistance calculated using the homeostasis model assessment as {[fasting serum insulin (mu U/ml)] X [fasting plasma glucose (mmol/L)]/22.5}. Results: The age- and sex-adjusted prevalence of diagnosed diabetes increased from 5.5% in 1988-1994 to 6.8% in 1999-2002 (change 1.3%, 95% confidence interval 0.5-2.1). Little change occurred in the adjusted prevalence of undiagnosed diabetes (from 3.0 to 3.0%) and impaired fasting glucose (from 26.2 to 26.9%). Mean insulin resistance and the proportion with high insulin resistance increased significantly both among normoglycemic persons (mean: from 2.0 to 2.2; proportion > 2.35: from 26.2 to 32.2%) and among persons with undiagnosed diabetes or impaired fasting glucose (mean: from 4.0 to 4.5; proportion > 4.4: from 24.8 to 31.1%). In 1999 to 2002, diagnosed and undiagnosed diabetes were most common in non-Hispanic blacks, whereas impaired fasting glucose was most common in Mexican Americans. Conclusions: Diabetes, impaired fasting glucose, and insulin resistance are common in the United States and their prevalence continues to increase. (c) 2007 Elsevier Inc. All rights reserved. C1 VA Puget Sound Hlth Care Syst, Dept Med, Res Enhancement Award Program, Seattle, WA 98108 USA. Univ Washington, Seattle, WA 98195 USA. VA Puget Sound Hlth Care Syst, Dept Med, Epidemiol Res & Informat Ctr, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Dept Med, Div Gastroenterol, Seattle, WA 98108 USA. VA Puget Sound Hlth Care Syst, Dept Med, Div Gen Internal Med, Seattle, WA 98108 USA. RP Ioannou, GN (reprint author), VA Puget Sound Hlth Care Syst, Dept Med, Res Enhancement Award Program, S-111-Gastro,1660 S Columbian Way, Seattle, WA 98108 USA. EM georgei@medicine.washington.edu NR 25 TC 26 Z9 28 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1056-8727 J9 J DIABETES COMPLICAT JI J. Diabetes Complications PD NOV-DEC PY 2007 VL 21 IS 6 BP 363 EP 370 DI 10.1016/j.jdiacomp.2006.07.005 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 229NR UT WOS:000250811500005 PM 17967708 ER PT J AU Inan, U Aydin, C Uzun, O Topuz, O Alacam, T AF Inan, Ugur Aydin, Cumhur Uzun, Ozgur Topuz, Ozgur Alacam, Tayfun TI Evaluation of the surface characteristics of used and new ProTaper instruments: An atomic force microscopy study SO JOURNAL OF ENDODONTICS LA English DT Article DE atomic force microscopy; clinical use; NiTi rotary instruments ID TITANIUM ROTARY INSTRUMENTS; CLINICAL-USE; CYCLIC FATIGUE; DEFECTS; FILES; PROFILE; SYSTEMS AB The purpose of this study was to evaluate the topography of new and used ProTaper rotary nickel-titanium (NiTi) instruments by using atomic force microscope. Four new and four used size S1, S2, F1, and F2 instruments were selected for this study. New and used instruments were analyzed on 11 points along a 3-mm section at the tip of the instrument. Quantitative measurements according to the topographic deviations (root mean square) were recorded. Data were analyzed by paired samples t test. Mean root mean square values for used ProTaper instruments were higher than the new ones, and the difference between them was statistically significant. The results of this study showed that used ProTaper instruments demonstrated more surface deformation and wear. C1 Ondokuz Mayis Univ, Dept Endodont & Restorat Dent, Fac Dent, Samsun, Turkey. Gulhane Mil Med Acad, Dept Endodont & Conservat Treatment, Ctr Dent Sci, Ankara, Turkey. Gazi Univ, Fac Dent, Dept Endodont & Conservat Treatment, Ankara, Turkey. RP Aydin, C (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, 50 Blossom St,Thier 10, Boston, MA 02114 USA. EM cumhuraydin@gata.edu.tr NR 22 TC 15 Z9 16 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0099-2399 J9 J ENDODONT JI J. Endod. PD NOV PY 2007 VL 33 IS 11 BP 1334 EP 1337 DI 10.1016/j.joen.2007.07.014 PG 4 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 228WW UT WOS:000250764300016 PM 17963958 ER PT J AU Hull, MJ Juhascik, M Mazur, F Flomenbaum, MA Behonick, GS AF Hull, Mindy J. Juhascik, Matthew Mazur, Frank Flomenbaum, Mark A. Behonick, George S. TI Fatalities associated with fentanyl and co-administered cocaine or opiates SO JOURNAL OF FORENSIC SCIENCES LA English DT Article DE forensic science; forensic toxicology; fentanyl; opiates; cocaine; drug abuse; overdose; fatality; autopsy ID TRANSDERMAL FENTANYL; UNITED-STATES; DEATHS; ABUSE; CIRCUMSTANCES; MISUSE AB Fatalities associated with fentanyl hydrochloride are increasingly seen in Massachusetts. Between September 2005 and November 2006, 5009 medicolegal investigations associated 107 deaths with licit or illicit fentanyl use, along with a co-detection of an opiate/opioid or cocaine/benzoylecognine, or both. Deaths associated with illicit fentanyl use occur in younger people (39.4 vs. 61.5 years) with higher fentanyl (17.1 ng/mL vs. 4.4 ng/mL) and lower morphine (76.9 ng/mL vs. 284.2 ng/mL) postmortem blood concentrations, and more frequent cocaine co-intoxication (65% vs. 3%), than deaths associated with licit fentanyl use. A wide range of postmortem blood concentrations of fentanyl was detected (trace-280 ng/mL), with a minimum concentration of 7 ng/mL of fentanyl strongly associated with illicit use of fentanyl in poly-drug cases. The most commonly detected opiates/opioids in illicit fentanyl users were: morphine (29%), oxycodone (14.5%), and methadone (14.5%). Ethanol, cannabinoids, diazepam, citalopram, and diphenhydramine were each detected in greater than 10% of the illicit fentanyl cases. Most fentanyl abusers died at their own home and their deaths were most often classified as accidental. Mapping of primary residences of decedents revealed conspicuous clustering of the illicit fentanyl use cases, as opposed to the random pattern in licit use cases. Fentanyl misuse is a public health problem in Massachusetts. C1 [Hull, Mindy J.; Flomenbaum, Mark A.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Juhascik, Matthew; Mazur, Frank; Behonick, George S.] UMass Mem Med Ctr, Dept Hosp Labs, Worcester, MA 01605 USA. [Flomenbaum, Mark A.] Off Chief Med Examiner, Boston, MA 02118 USA. RP Behonick, GS (reprint author), DABFT, UMass Forens Toxicol Lab, 1 Innovat Dr,3rd Floor,Suite 360, Worcester, MA 01605 USA. EM behonicg@ummhc.org NR 19 TC 24 Z9 27 U1 3 U2 12 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-1198 J9 J FORENSIC SCI JI J. Forensic Sci. PD NOV PY 2007 VL 52 IS 6 BP 1383 EP 1388 DI 10.1111/j.1556-4029.2007.00564.x PG 6 WC Medicine, Legal SC Legal Medicine GA 239YH UT WOS:000251553700024 PM 17944902 ER PT J AU Tatum, RP Wong, JA Figueredo, EJ Martin, V Oelschlager, BK AF Tatum, Roger P. Wong, Jamie A. Figueredo, Edgar J. Martin, Valeria Oelschlager, Brant K. TI Return of esophageal function after treatment for Achalasia as determined by impedance-manometry SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Article; Proceedings Paper CT 48th Annual Meeting of the Society-for-Surgery-of-the-Alimentary-Tract CY MAY 19-23, 2007 CL Washington, DC SP Soc Surg Alimentary Tract DE Achalasia; Heller myotomy; esophageal motility; multichannel intraluminal impedance ID MULTICHANNEL INTRALUMINAL IMPEDANCE; IDIOPATHIC ACHALASIA; HELLERS MYOTOMY; PNEUMATIC DILATATION; FORCEFUL DILATATION; PERISTALSIS; ESOPHAGOMYOTOMY; ABNORMALITIES; MOTILITY; MODEL AB Background Treatment for Achalasia is aimed at the lower esophageal sphincter (LES), although little is known about the effect, if any, of these treatments on esophageal body function (peristalsis and clearance). We sought to measure the effect of various treatments using combined manometry (peristalsis) with Multichannel Intraluminal Impedance (MII) (esophageal clearance). Methods We enrolled 56 patients with Achalasia referred to the University of Washington Swallowing Center between January 2003 and January 2006. Each was grouped according to prior treatment: 38 were untreated (untreated achalasia), 10 had undergone botox injection or balloon dilation (endoscopic treatment), and 16 a laparoscopic Heller myotomy. The preoperative studies for 8 of the myotomy patients were included in the untreated achalasia group. Each patient completed a dysphagia severity questionnaire (scale 0-10). Peristalsis was analyzed by manometry and esophageal clearance of liquid and viscous material by MII. Results Mean dysphagia severity scores were significantly better in patients after Heller Myotomy than in either of the other groups (2.0 vs. 5.3 in the endoscopic group and 6.5 in untreated achalasia, p < 0.05). Peristaltic contractions were observed in 63% of patients in the Heller myotomy group, compared with 40% in the endoscopic group and 8% in untreated achalasia (p < 0.05 for both treatment groups vs. untreated achalasia). Liquid clearance rates were significantly better in both treatment groups: 28% in Heller myotomy and 16% in endoscopic treatment compared to only 5% in untreated achalasia (p < 0.05). Similarly, viscous clearance rates were 19% in Heller myotomy and 11% in endoscopic treatment, vs. 2% in untreated achalasia (p < 0.05). In the subset of patients who underwent manometry/MII both pre- and postoperatively, peristalsis was observed more frequently postoperatively than in preop studies (63% of patients exhibiting peristalsis vs. 12%), as was complete clearance of liquid (35% of swallows vs. 14%) and viscous boluses (22% of swallows vs. 14%). These differences were not significant, however. In the patients who had a myotomy the return of peristalsis correlates with effective esophageal clearance (liquid bolus: r=0.46, p=0.09 and viscous bolus: r=0.63, < 0.05). There is no correlation between peristalsis and bolus clearance in the endoscopic treatment group. Conclusions With treatment Achalasia patients exhibit some restoration in peristalsis as well as improved bolus clearance. After Heller Myotomy, the return of peristalsis correlates with esophageal clearance, which may partly explain its superior relief of dysphagia. C1 Univ Washington, Dept Surg, VA Puget Sound HCS, Seattle, WA 98108 USA. RP Tatum, RP (reprint author), Univ Washington, Dept Surg, VA Puget Sound HCS, 1660 S Columbian Way,S-112-Gs, Seattle, WA 98108 USA. EM rtatum@u.washington.edu NR 27 TC 13 Z9 14 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1091-255X J9 J GASTROINTEST SURG JI J. Gastrointest. Surg. PD NOV PY 2007 VL 11 IS 11 BP 1403 EP 1409 DI 10.1007/s11605-007-0293-x PG 7 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 217XF UT WOS:000249979900006 PM 17786525 ER PT J AU Bilimoria, KY Tomlinson, JS Merkow, RP Stewart, AK Ko, CY Talamonti, MS Bentrem, DJ AF Bilimoria, Karl Y. Tomlinson, James S. Merkow, Ryan P. Stewart, Andrew K. Ko, Clifford Y. Talamonti, Mark S. Bentrem, David J. TI Clinicopathologic features and treatment trends of pancreatic neuroendocrine tumors: Analysis of 9,821 patients SO JOURNAL OF GASTROINTESTINAL SURGERY LA English DT Article DE pancreatic neuroendocrine tumors; surgery; pancreatectomy; National Cancer Data Base ID ISLET-CELL-CARCINOMA; PROGNOSTIC-FACTORS; CONSECUTIVE PANCREATICODUODENECTOMIES; ENDOCRINE TUMORS; HOSPITAL VOLUME; SURVIVAL; SURGERY; CANCER; EXPERIENCE; ADENOCARCINOMA AB The natural history of pancreatic neuroendocrine tumors ( PNET) remains poorly defined. Our objectives were to examine the clinicopathologic features of PNETs, to assess treatment trends over time, and to identify factors associated with undergoing resection. From the National Cancer Data Base (1985-2004), 9,821 patients were identified with PNETs. Clinicopathologic features and treatment trends were examined. Multivariable logistic regression was used to assess factors associated with undergoing resection. Of 9,821 patients with PNETs, 85% were nonfunctional, 7.1% were functional, and 7.9% were carcinoid tumors. Of the 3,851 (39.0%) patients who underwent pancreatectomy, 449 (11.7%) received adjuvant chemotherapy, and 254 (6.6%) received adjuvant radiation. From 1985 to 2004, utilization of pancreatectomy increased from 39.4 to 44.3% (P < 0.0001). Patients were less likely to undergo resection if they were > 55 years old, had tumors in the head of the pancreas, tumors >= 4 cm, or had distant metastases (P < 0.0001). Patients treated at NCCN/NCI, academic, or high-volume hospitals were more likely to undergo resection. There are disparities in the utilization of pancreatectomy for PNETs. As PNETs have a better prognosis than adenocarcinoma, concerns regarding the morbidity and mortality of pancreatic surgery and neoplasms should not preclude resection. C1 Northwestern Univ, Northwestern Mem Hosp, Feinberg Sch Med, Dept Surg,Div Surg Oncol, Chicago, IL 60611 USA. Amer Coll Surg, Canc Programs, Chicago, IL USA. Univ Calif Los Angeles, Dept Surg, Los Angeles, CA USA. VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Bentrem, DJ (reprint author), Northwestern Univ, Northwestern Mem Hosp, Feinberg Sch Med, Dept Surg,Div Surg Oncol, 675 N St Clair,Galter 10-105, Chicago, IL 60611 USA. EM dbentrem@nmff.org NR 41 TC 61 Z9 71 U1 0 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1091-255X J9 J GASTROINTEST SURG JI J. Gastrointest. Surg. PD NOV PY 2007 VL 11 IS 11 BP 1460 EP 1467 DI 10.1007/s11605-007-0263-3 PG 8 WC Gastroenterology & Hepatology; Surgery SC Gastroenterology & Hepatology; Surgery GA 217XF UT WOS:000249979900019 PM 17846854 ER PT J AU Cheng, EM Chen, A Cunningham, W AF Cheng, Eric M. Chen, Alex Cunningham, William TI Primary language and receipt of recommended health care among Hispanics in the United States SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE disparities; Hispanic health; language barriers ID MEDICARE BENEFICIARIES; PREVENTIVE SERVICES; WOMEN; VACCINATION; DISPARITIES; POPULATION; BARRIERS; ACCESS AB Background: Disparities in health care services between Hispanics and whites in the United States are well documented. Objective: The objective of the study was to determine whether language spoken at home identifies Hispanics at risk for not receiving recommended health care services. Design. The design of the study was cross-sectional, nationally representative survey of households. Patients: The patients were non-Hispanic white and Hispanic adults participating in the 2003 Medical Expenditure Panel Survey. Measurements: We compared receipt of ten recommended health care services by ethnicity and primary language adjusting for demographic and socioeconomic characteristics, health status, and access to care. Results: The sample included 12,706 whites and 5,500 Hispanics. In bivariate comparisons, 57.0% of whites received all eligible health care services compared to 53.6% for Hispanics who spoke English at home, 44.9% for Hispanics who did not speak English at home but who were comfortable speaking English, and 35.0% for Hispanics who did not speak English at home and were uncomfortable speaking English (p <.001). In multivariate logistic models, compared to non-Hispanic whites, Hispanics who did not speak English at home were less likely to receive all eligible health care services, whether they were comfortable speaking English (risk ratio [RR] 0.88, 95% confidence interval [CI] 0.74-0.97) or not (RR 0.84, 95% Cl 0.68-0.95). Conclusions: Speaking a language other than English at home identified Hispanics at risk for not receiving recommended health care services, whether they were comfortable in speaking English or not. Identifying the mechanism for disparities by language usage may lead to interventions to reduce ethnic disparities. C1 VA Greater Los Angeles Healthcare Syst, Los Angeles, CA 90073 USA. VA Greater Los Angeles, Dept Neurol, Los Angeles, CA USA. Univ Calif Los Angeles, Sch Med, Dept Neurol, Los Angeles, CA 90024 USA. Univ So Calif, Dept Pediat, Los Angeles, CA 90089 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA 90024 USA. RP Cheng, EM (reprint author), VA Greater Los Angeles Healthcare Syst, 11301 Wilshire Blvd,B500 ML 127, Los Angeles, CA 90073 USA. EM eric.cheng@va.gov FU NIMHD NIH HHS [P20 MD000148, P20 MD000182, P20MD000148, P20MD000182] NR 24 TC 83 Z9 83 U1 1 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD NOV PY 2007 VL 22 SU 2 BP 283 EP 288 DI 10.1007/s11606-007-0346-6 PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 230HI UT WOS:000250866700004 PM 17957412 ER PT J AU Ngo-Metzger, Q Sorkin, DH Phillips, RS Greenfield, S Massagli, MP Clarridge, B Kaplan, SH AF Ngo-Metzger, Quyen Sorkin, Dara H. Phillips, Russell S. Greenfield, Sheldon Massagli, Michael P. Clarridge, Brian Kaplan, Sherrie H. TI Providing high-quality care for limited English proficient patients: The importance of language concordance and interpreter use SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE quality of care; satisfaction; interpersonal care; interpreters; health education; language barriers; limited English proficiency; Asian American ID MEDICAID MANAGED CARE; SPANISH-SPEAKING PATIENTS; HEALTH-CARE; EMERGENCY-DEPARTMENT; ASIAN-AMERICANS; UNITED-STATES; BARRIERS; ASSESSMENTS; IMPACT; SATISFACTION AB Background: Provider-patient language discordance is related to worse quality care for limited English proficient (LEP) patients who speak Spanish. However, little is known about language barriers among LEP Asian-American patients. Objective: We examined the effects of language discordance on the degree of health education and the quality of interpersonal care that patients received, and examined its effect on patient satisfaction. We also evaluated how the presence/absence of a clinic interpreter affected these outcomes. Design: Cross-sectional survey, response rate 74%. Participants: A total of 2,746 Chinese and Vietnamese patients receiving care at I I health centers in 8 cities. Measurements: Provider-patient language concordance, health education received, quality of interpersonal care, patient ratings of providers, and the presence/absence of a clinic interpreter. Regression analyses were used to adjust for potential confounding. Results: Patients with language-discordant providers reported receiving less health education (beta=0.17, p < 0.05) compared to those with language-concordant providers. This effect was mitigated with the use of a clinic interpreter. Patients with language-discordant providers also reported worse interpersonal care (beta-0.28, p < 0.05), and were more likely to give low ratings to their providers (odds ratio [OR]=1.61; CI=0.97-2.67). Using a clinic interpreter did not mitigate these effects and in fact exacerbated disparities in patients' perceptions of their providers. Conclusion: Language barriers are associated with less health education, worse interpersonal care, and lower patient satisfaction. Having access to a clinic interpreter can facilitate the transmission of health education. However, in terms of patients' ratings of their providers and the quality of interpersonal care, having an interpreter present does not serve as a substitute for language concordance between patient and provider. C1 Univ Calif Irvine, Div Gen Internal Med & Primary Care, Acad 3, Sch Med, Irvine, CA 92697 USA. Univ Calif Irvine, Ctr Hlth Policy Res, Acad 3, Sch Med, Irvine, CA 92697 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Gen Internal Med & Primary Care, Boston, MA USA. Univ Massachusetts, Survey Res Ctr, Boston, MA 02125 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Ngo-Metzger, Q (reprint author), Univ Calif Irvine, Div Gen Internal Med & Primary Care, Acad 3, Sch Med, Suite 220, Irvine, CA 92697 USA. EM Qhngo@uci.edu FU AHRQ HHS [R01-HS10316, R01 HS010316] NR 44 TC 107 Z9 107 U1 5 U2 15 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD NOV PY 2007 VL 22 SU 2 BP 324 EP 330 DI 10.1007/s11606-007-0340-z PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 230HI UT WOS:000250866700011 PM 17957419 ER PT J AU Gregg, J Saha, S AF Gregg, Jessica Saha, Somnath TI Communicative competence: A framework for understanding language barriers in health care SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Editorial Material C1 Oregon Hlth & Sci Univ, Div Gen Internal Med & Geriatr, Portland, OR 97201 USA. Oregon Hlth & Sci Univ, Div Gen Internal Med & Geriatr, Gen Internal Med Sect, Portland VA Med Ctr, Portland, OR USA. RP Gregg, J (reprint author), Oregon Hlth & Sci Univ, Div Gen Internal Med & Geriatr, 3181 SW Sam Jackson Pk Rd L-475, Portland, OR 97201 USA. EM greggj@ohsu.edu NR 30 TC 17 Z9 17 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD NOV PY 2007 VL 22 SU 2 BP 368 EP 370 DI 10.1007/s11606-007-0364-4 PG 3 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 230HI UT WOS:000250866700020 PM 17957428 ER PT J AU Trinacty, CM Adams, AS Soumerai, SB Zhang, F Meigs, JB Piette, JD Ross-Degnan, D AF Trinacty, Connie Mah Adams, Alyce S. Soumerai, Stephen B. Zhang, Fang Meigs, James B. Piette, John D. Ross-Degnan, Dennis TI Racial differences in long-term self-monitoring practice among newly drug-treated diabetes patients in an HMO SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE racial disparities; self-management; diabetes; HMO ID BLOOD-GLUCOSE CONTROL; GLYCEMIC CONTROL; CONTROLLED-TRIAL; METABOLIC CONTROL; AFRICAN-AMERICAN; COMPLICATIONS; MANAGEMENT; MELLITUS; POPULATION; CARE AB BACKGROUND: One approach to improving outcomes for minority diabetics may be through better self-care. However, minority patients may encounter barriers to better self-care even within settings where variations in quality of care and insurance are minimized. OBJECTIVE:The objective of the study was to evaluate racial differences in long-term glucose self-monitoring and adherence rates in an HMO using evidence-based guidelines for self-monitoring. DESIGN: Retrospective cohort study using 10 years (1/1/1993-12/31/2002) of electronic medical record data was used. PATIENTS: Patients were 1,732 insured adult diabetics of black or white race newly initiated on hypoglycemic therapy in a large multi-specialty care group practice. MEASUREMENTS: Outcomes include incidence and prevalence of glucose self-monitoring, intensity of use, and rate of adherence to national recommended standards. RESULTS: We found no evidence of racial differences in adjusted initiation rates of glucose self-monitoring among insulin-treated patients, but found lower rates of initiation among black patients living in low-income areas. Intensity of glucose self-monitoring remained lower among blacks than whites throughout follow-up [IRR for insulin=0.41 (0.27-0.62); IRR for oral hypoglycemic=0.75 (0.63, 0.90)], with both groups monitoring well below recommended standards. Among insulin-treated patients, < 1% of blacks and < 10% of whites were self-monitoring 3 times per day; 36% of whites and 10% of blacks were self-monitoring at least once per day. CONCLUSIONS: Adherence to glucose self-monitoring standards was low, particularly among blacks, and racial differences in self-monitoring persisted within a health system providing equal access to services for diabetes patients. Early and continued emphasis on adherence among black diabetics may be necessary to reduce racial differences in long-term glucose self-monitoring. C1 Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA 02215 USA. Harvard Piligrim Hlth Care, Boston, MA 02215 USA. Massachusetts Gen Hosp, Gen Med Unit, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Michigan Hlth Care Syst, Div Gen Med, Ann Arbor, MI USA. HSR&D VA Ann Arbor Hlth Care Syst, Ctr Practice Management & Outcomes Res, Ann Arbor, MI USA. RP Trinacty, CM (reprint author), Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, 133 Brookline Ave,6th Floor, Boston, MA 02215 USA. EM connie_trinacty@hphc.org NR 37 TC 16 Z9 16 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD NOV PY 2007 VL 22 IS 11 BP 1506 EP 1513 DI 10.1007/s11606-007-0339-5 PG 8 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 220EH UT WOS:000250139200004 PM 17763913 ER PT J AU Lown, BA Chou, CL Clark, WD Haidet, P Kemp, M Krupat, E Pelletier, S Weissmann, P Anderson, MB AF Lown, Beth A. Chou, Calvin L. Clark, William D. Haidet, Paul Kemp, Maysel Krupat, Edward Pelletier, Stephen Weissmann, Peter Anderson, M. Brownell TI Caring attitudes in medical education: Perceptions of deans and curriculum leaders SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 117th Annual Meeting of the Association-of-American-Medical-Colleges CY OCT 30, 2006 CL Seattle, WA SP Assoc Amer Med Coll DE caring attitudes; medical education; hidden curriculum; professionalism ID PHYSICIAN-PATIENT COMMUNICATION; PRIMARY-CARE PHYSICIANS; INFORMAL CURRICULUM; PERSONAL AWARENESS; HIDDEN CURRICULUM; STUDENTS; BEHAVIOR; SCHOOLS; VALUES; EXPERIENCES AB BACKGROUND: Systems of undergraduate medical education and patient care can create barriers to fostering caring attitudes. OBJECTIVE: The aim of this study is to survey associate deans and curriculum leaders about teaching and assessment of caring attitudes in their medical schools. PARTICIPANTS: The participants of this study include 134 leaders of medical education in the USA and Canada. METHODS: We developed a survey with 26 quantitative questions and 1 open-ended question. In September to October 2005, the Association of American Medical Colleges distributed it electronically to curricular leaders. We used descriptive statistics to analyze quantitative data, and the constant comparison technique for qualitative analysis. RESULTS: We received 73 responses from 134 medical schools. Most respondents believed that their schools strongly emphasized caring attitudes. At the same time, 35% thought caring attitudes were emphasized less than scientific knowledge. Frequently used methods to teach caring attitudes included small-group discussion and didactics in the preclinical years, role modeling and mentoring in the clinical years, and skills training with feedback throughout all years. Barriers to fostering caring attitudes included time and productivity pressures and lack of faculty development. Respondents with supportive learning environments were more likely to screen applicants' caring attitudes, encourage collaborative learning, give humanism awards to faculty, and provide faculty development that emphasized teaching of caring attitudes. CONCLUSIONS: The majority of educational leaders value caring attitudes, but overall, educational systems inconsistently foster them. Schools may facilitate caring learning environments by providing faculty development and support, by assessing students and applicants for caring attitudes, and by encouraging collaboration. C1 Mt Auburn Hosp, Dept Med, Cambridge, MA 02238 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Amer Acad Commun Healthcare, Chesterfield, MO USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Vet Adm Med Ctr, San Francisco, CA 94121 USA. Baylor Coll Med, Houston, TX 77030 USA. Michael E DeBakey Vet Affairs Med Ctr, Houston, TX USA. LLC, Healthcare Qual & Commun Improvement, Chester, CT USA. Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA. Hennepin Cty Med Ctr, Minneapolis, MN 55415 USA. Assoc Amer Med Coll, Washington, DC USA. RP Lown, BA (reprint author), Mt Auburn Hosp, Dept Med, Cambridge, MA 02238 USA. EM blown@mah.harvard.edu NR 39 TC 18 Z9 19 U1 3 U2 12 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD NOV PY 2007 VL 22 IS 11 BP 1514 EP 1522 DI 10.1007/s11606-007-0318-x PG 9 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 220EH UT WOS:000250139200005 PM 17786522 ER PT J AU Hu, JC Link, CL McNaughton-Collins, M Barry, MJ McKinlay, JB AF Hu, Jim C. Link, Carol L. McNaughton-Collins, Mary Barry, Michael J. McKinlay, John B. TI The association of abuse and symptoms suggestive of chronic prostatitis/chronic pelvic pain syndrome: Results from the Boston Area Community Health survey SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE chronic prostatitis; abuse; epidemiology ID CHILD SEXUAL ABUSE; NATIONAL COMORBIDITY SURVEY; PHYSICAL ABUSE; GENERAL-POPULATION; ASSAULT HISTORY; BACK-PAIN; GASTROINTESTINAL DISORDERS; CLINICAL CHARACTERISTICS; WOMEN; PREVALENCE AB OBJECTIVE: To determine the effect of reported sexual, physical, or emotional abuse on the symptoms suggestive of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and to determine the effect of race/ethnicity on these patterns. METHODS: The Boston Area Community Health (BACH) survey used a multi-stage stratified cluster sample to randomly sample 5,506 adults aged 30-79 from the city of Boston. BACH recruited 2,301 men (700 Black, 766 Hispanic, and 835 White). Interviewers administered questions approximating the National Institutes of Health chronic prostatitis symptom index (CPSI), and symptoms suggestive of CP/CPPS were measured by the definition of perineal and/or ejaculatory pain and CPSI pain score of 4+. Questions about previous abuse were obtained from a validated self-administered questionnaire during the home visit. Logistic regression was used to determine the effect of abuse on the likelihood of a man having symptoms suggestive of CP/CPPS. RESULTS: The prevalence of symptoms suggestive of CP/CPPS was 6.5%. Men who reported having experienced sexual, physical, or emotional abuse had increased odds (1.7-3.3) for symptoms suggestive of CP/CPPS. Previous abuse increased both the pain and urinary scores from the CPSI. CONCLUSION: Symptoms suggestive of CP/CPPS are not uncommon in a community-based population of men. For men presenting with symptoms suggestive of CP/CPPS, clinicians may wish to consider screening for abuse. C1 Brigham & Womens Hosp, Div Urol Surg, Boston, MA 02115 USA. Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. New England Res Inst, Watertown, MA 02172 USA. RP Hu, JC (reprint author), Brigham & Womens Hosp, Div Urol Surg, 75 Francis St, Boston, MA 02115 USA. EM jhu2@partners.org FU NIDDK NIH HHS [U01 DK056842, U01DK56842] NR 52 TC 27 Z9 29 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD NOV PY 2007 VL 22 IS 11 BP 1532 EP 1537 DI 10.1007/s11606-007-0341-y PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 220EH UT WOS:000250139200008 PM 17763912 ER PT J AU Smith, AK Davis, RB Krakauer, EL AF Smith, Alexander K. Davis, Roger B. Krakauer, Eric L. TI Differences in the quality of the patient-physician relationship among terminally ill African-American and white patients: Impact on advance care planning and treatment preferences SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE end-of-life care; race/ethnicity; trust; patient-physician relationship ID OF-LIFE CARE; NOT-RESUSCITATE ORDERS; BLACK-AND-WHITE; RACIAL-DIFFERENCES; SUSTAINING TREATMENTS; HEALTH-CARE; END; RACE; COMMUNICATION; PERCEPTIONS AB BACKGROUND: Little is known about the quality of the patient-physician relationship for terminally ill African Americans. OBJECTIVE: To compare the quality of the patient-physician relationship between African-American and white patients and examine the extent to which relationship quality contributes to differences in advance care planning (ACP) and preferences for intensive life-sustaining treatment (LST). DESIGN: Cross sectional survey of 803 terminally ill African-American and white patients. MEASUREMENTS: Patient-reported quality of the patient-physician relationship (degree of trust, perceived respect, and joint decision making; skill in breaking bad news and listening; help in navigating the medical system), ACP, preferences for LST (cardiopulmonary resuscitation, major surgery, mechanical ventilation, and dialysis). RESULTS: The quality of the patient-physician relationship was worse for African Americans than for white patients by all measures except trust. African Americans were less likely to have an ACP (adjusted relative risk [aRR]=0.66, 95%CI=0.52-0.84), and were more likely to have a preference for cardiopulmonary resuscitation and dialysis (aRR=1.28, 95%CI=1.03-1.58; aRR=1.25, 95%CI=1.07-1.47, respectively). Additional adjustment for the quality of the patient-physician relationship had no impact on the differences in ACP and treatment preferences. CONCLUSIONS: Lower reported patient-physician relationship quality for African-American patients does not explain the observed differences between African Americans and whites in ACP and preferences for LST. C1 Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Brookline, MA 02446 USA. Dana Farber Canc Inst, Div Psychol Oncol & Palliat Care, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Social Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Palliat Care Serv, Boston, MA 02114 USA. RP Smith, AK (reprint author), Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, 1309 Beacon St, Brookline, MA 02446 USA. EM asmith7@bidmc.harvard.edu FU PHS HHS [5 T32 HP11001-19] NR 29 TC 27 Z9 27 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD NOV PY 2007 VL 22 IS 11 BP 1579 EP 1582 DI 10.1007/s11606-007-0370-6 PG 4 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 220EH UT WOS:000250139200015 PM 17879120 ER PT J AU Berg, KM Gill, TM Brown, AF Zerzan, J Elmore, JG Wilson, IB AF Berg, Karina M. Gill, Thomas M. Brown, Arleen F. Zerzan, Judy Elmore, Joann G. Wilson, Ira B. TI Demystifying the NIH grant application process SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Review DE clinical research; academic medicine; NIH; funding; grants ID CLINICAL-RESEARCH AB The process of applying to the National Institutes of Health (NIH) for grant funding can be daunting. The objective of this article is to help investigators successfully navigate the NIH grant application process. We focus on the practical aspects of this process, which are commonly learned through trial and error. Our target audience is generalist faculty and fellows who are applying for NIH funding to support their career development or a clinical research project. C1 Tufts Univ New England Med Ctr, Dept Med, Boston, MA 02111 USA. Albert Einstein Coll Med, Div Gen Internal Med, Bronx, NY 10467 USA. Montefiore Med Ctr, Bronx, NY 10467 USA. Yale Univ, Sch Med, New Haven, CT USA. Univ Calif Los Angeles, Div Gen Internal Med, Los Angeles, CA USA. Univ Calif Los Angeles, Hlth Serv Res, Los Angeles, CA USA. VA Puget Sound Health Care Syst, Hlth Serv Res & Dev, Seattle, WA USA. Univ Washington, Harborview Med Ctr, Sch Med, Seattle, WA 98104 USA. Tufts Univ New England Med Ctr, Inst Clin Res & Hlth Policy Studies, Boston, MA USA. RP Wilson, IB (reprint author), Tufts Univ New England Med Ctr, Dept Med, 750 Washington St,Box 345, Boston, MA 02111 USA. EM iwilson@tufts-nemc.org RI Wilson, Ira/F-9190-2016 OI Wilson, Ira/0000-0002-0246-738X FU NCI NIH HHS [K05 CA104699, K05 CA104699-07]; NCRR NIH HHS [K24 RR020300]; NIA NIH HHS [K23 AG 026748, K23 AG026748, K24 AG021507, K24AG021507]; NIDA NIH HHS [K23 DA021087, K23 DA 021087] NR 25 TC 5 Z9 5 U1 0 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD NOV PY 2007 VL 22 IS 11 BP 1587 EP 1595 DI 10.1007/s11606-007-0301-6 PG 9 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 220EH UT WOS:000250139200017 PM 17687616 ER PT J AU Benton, N Harvath, TA Flaherty-Robb, M Medcraft, M Mcwhorter, K Mcclelland, F Joseph, C Mambourg, F AF Benton, Nancy Harvath, Theresa A. Flaherty-Robb, Marna Medcraft, Marijo Mcwhorter, Karen Mcclelland, Faith Joseph, Carol Mambourg, Floris TI Managing - Chronic, nonhealing wounds SO JOURNAL OF GERONTOLOGICAL NURSING LA English DT Article ID CHRONIC VENOUS INSUFFICIENCY; LEG ULCERS AB The physical, emotional, and financial costs of caring for patients with chronic, nonhealing leg wounds are substantial. In fiscal year 200, the home care department of a large Veterans Affairs medical center in the Pacific Northwest spent nearly half of its annual budget on veterans needing wound care. In this article, the authors describe a practice improvement project designed to improve the wound care management of homebound veterans with chronic, nonnealing lower extremity wound using a research-based protocol and consultation by a certified wound care specialist. as well as the effect of this program on home care expenditures. C1 Oregon Hlth & Sci Univ, Sch Nursing, Portland, OR 97239 USA. Portland VA Med Ctr, Nursing Skilled Care Unit, Portland, OR 97239 USA. Portland VA Med Ctr, Home & Community Based Serv, Portland, OR 97239 USA. Oregon Hlth & Sci Univ, Hosp & Clin, Portland, OR 97201 USA. RP Harvath, TA (reprint author), Oregon Hlth & Sci Univ, Sch Nursing, 3455 SW US Vet Rd,SN-6S, Portland, OR 97239 USA. EM harvatbt@ohsu.edu NR 19 TC 7 Z9 7 U1 1 U2 3 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0098-9134 J9 J GERONTOL NURS JI J. Gerontol. Nurs. PD NOV PY 2007 VL 33 IS 11 BP 38 EP 45 PG 8 WC Geriatrics & Gerontology; Gerontology; Nursing SC Geriatrics & Gerontology; Nursing GA 230NX UT WOS:000250884300006 PM 18019117 ER PT J AU Crandall, LG White, DL Schuldheis, S Talerico, KA AF Crandall, Lynda G. White, Diana L. Schuldheis, Sherrie Talerico, Karen Amann TI Initiating Person-Centered care practices in long-term care facilities SO JOURNAL OF GERONTOLOGICAL NURSING LA English DT Article ID NURSING-HOME; TRIAL; MODEL AB Person-centered care is a key concept guiding efforts to improve long-term care. Elements of person-centered care include personhood, knowing the person, maximizing choice and autonomy, comfort, nurturing relationships, and a supportive physical and organizational environment. The Oregon Health & Science University Hartford Center of Geriatric Nursing Excellence and the state agency that oversees health care for older adults worked in partnership with 9 long-term care facilities. Each developed and implemented person-centered care practices, including those focused on bathing, dining, or gardening. This article describes the processes used to develop and support these practices. Three exemplary facilities made significant practice changes, 4 made important but more moderate changes, and 2 made minimal progress. These facilities differed in terms of existing culture, management practices, staff involvement, and attention to sustainability. C1 Oregon Hlth & Sci Univ, Portland, OR 97239 USA. Portland VA Med Ctr, Portland, OR USA. Amann Talerico Consulting, Portland, OR USA. RP White, DL (reprint author), Oregon Hlth & Sci Univ, 3455 SW US Vet Rd,SN-6S, Portland, OR 97239 USA. EM whitedi@ohsu.edu NR 29 TC 37 Z9 37 U1 1 U2 14 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0098-9134 J9 J GERONTOL NURS JI J. Gerontol. Nurs. PD NOV PY 2007 VL 33 IS 11 BP 47 EP 56 PG 10 WC Geriatrics & Gerontology; Gerontology; Nursing SC Geriatrics & Gerontology; Nursing GA 230NX UT WOS:000250884300007 PM 18019118 ER PT J AU Taylor-Clark, K Koh, H Viswanath, K AF Taylor-Clark, Kalahn Koh, Howard Viswanath, K. TI Perceptions of environmental health risks and communication barriers among Low-SEP and racial/ethnic minority communities SO JOURNAL OF HEALTH CARE FOR THE POOR AND UNDERSERVED LA English DT Article DE focus groups; health communication; communication barriers; communication inequality; health disparities; environmental health ID RACE; DIFFERENTIALS; DISPARITIES; QUALITY; JUSTICE; IMPACT AB Despite a disproportionate burden of environmental hazards in lower socioeconomic positions (SEP) and racial/ethnic minority communities, research suggests that such communities may have concerns about environmental risks different from those of their higher SEP and White counterparts. These groups also face disproportionate barriers to accessing and utilizing public health information. Little work has focused on the environmental risk communication barriers that low-SEP minorities face. This paper reports on the results of seven focus groups conducted in three low-SEP Massachusetts communities, with an over-sample of racial/ethnic minorities. We explored (1) definitions of the environment, (2) perceptions of environmental health effects, (3) information-seeking behaviors around these issues, and (4) challenges to accessing and utilizing information. The local environment shapes these communities' perceptions of environmental risks; they face considerable barriers to accessing, understanding, and utilizing other sources of information about environmental health risks. We discuss the implications for future targeted campaigns to reduce negative impacts of environmental health risks. C1 Harvard Univ, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Taylor-Clark, K (reprint author), Harvard Univ, Dana Farber Canc Inst, 375 Longwood Ave,Suite 747, Boston, MA 02115 USA. EM ktaylor@hsph.harvard.edu NR 38 TC 12 Z9 12 U1 1 U2 10 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4363 USA SN 1049-2089 J9 J HEALTH CARE POOR U JI J. Health Care Poor Underserved PD NOV PY 2007 VL 18 IS 4 SU S BP 165 EP 183 DI 10.1353/hpu.2007.0113 PG 19 WC Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 239EQ UT WOS:000251502000011 PM 18065858 ER PT J AU Harte, BJ Dhaliwal, G Armstrong, W Pile, JC AF Harte, Brian J. Dhaliwal, Gurpreet Armstrong, Wendy Pile, James C. TI A rash decision SO JOURNAL OF HOSPITAL MEDICINE LA English DT Editorial Material ID HUMAN-IMMUNODEFICIENCY-VIRUS; UNKNOWN ORIGIN; SECONDARY SYPHILIS; FEVER; DIAGNOSIS C1 [Harte, Brian J.] Cleveland Clin, Dept Hosp Med, Cleveland, OH 44195 USA. [Dhaliwal, Gurpreet] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Dhaliwal, Gurpreet] San Francisco VA Med Ctr, Dept Med, San Francisco, CA USA. [Armstrong, Wendy] Emory Univ, Sch Med, Dept Infect Dis, Atlanta, GA USA. [Pile, James C.] Case Western Reserve Univ, Dept Med, Cleveland, OH 44106 USA. RP Harte, BJ (reprint author), Cleveland Clin, Dept Hosp Med, Desk S70,9500 Euclid Ave, Cleveland, OH 44195 USA. EM harteb@ccf.org RI Armstrong, Wendy/N-3623-2013 NR 15 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1553-5592 J9 J HOSP MED JI J. Hosp. Med. PD NOV-DEC PY 2007 VL 2 IS 6 BP 433 EP 438 DI 10.1002/jhm.253 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 292IA UT WOS:000255258500012 PM 18081174 ER PT J AU Venanzi, ES Gray, DHD Benoist, C Mathis, D AF Venanzi, Emily S. Gray, Daniel H. D. Benoist, Christophe Mathis, Diane TI Lymphotoxin pathway and Aire influences on thymic medullary epithelial cells are unconnected SO JOURNAL OF IMMUNOLOGY LA English DT Article ID PROMISCUOUS GENE-EXPRESSION; PROTEIN-KINASE PATHWAY; DEFICIENT MICE; BETA-RECEPTOR; CENTRAL TOLERANCE; T-CELLS; DIFFERENTIATION; ALPHA; ORGANOGENESIS; AUTOIMMUNITY AB The lymphotoxin pathway is critical for the development and maintenance of peripheral lymphoid organs. Mice with deficiencies in members of this pathway lack lymph nodes and Peyer's patches and have abnormal spleen architecture. These animals also develop autoantibodies to and lymphocytic infiltrates of multiple organs, provoking speculation that the lymphotoxin pathway may play a role in central tolerance induction. Indeed, a series of reports has claimed that lymphotoxin signals control the expression of Aire, a transcriptional regulator that is expressed in medullary epithelial cells of the thymus, mediates ectopic transcription of genes encoding a variety of peripheral tissue Ags, and promotes clonal deletion of self-reactive thymocytes. However, one report argued that lymphotoxin signals regulate the composition and organization of the thymus, particularly of the medullary epithelial compartment. Herein, we resolve this controversy in favor of the latter view. The expression and function of Aire were unaffected in medullary epithelial cells of mice lacking either lymphotoxin beta receptor or the lymphotoxin a-chain, and there was minimal overlap between the sets of genes controlled by Aire and lymphotoxin. Instead, both knockout lines showed abnormal medullary epithelial cell organization, and the line lacking the beta receptor had significantly fewer medullary epithelial cells. In short, the lymphotoxin pathway drives the developmental rather than selectional properties of thymic stromal cells. C1 Brigham & Womens Hosp, Joslin Diabet Ctr, Sect Immunol & Immunogenet, Dept Med, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Benoist, C (reprint author), Joslin Diabet Ctr, Sect Immunol & Immunogenet, 1 Joslin Pl, Boston, MA 02215 USA. EM cbdm@joslin.harvard.edu RI Gray, Daniel/A-3293-2013 OI Gray, Daniel/0000-0002-8457-8242 FU NIDDK NIH HHS [R01 DK60027, T32 DK07260] NR 44 TC 60 Z9 62 U1 3 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 2007 VL 179 IS 9 BP 5693 EP 5700 PG 8 WC Immunology SC Immunology GA 223QS UT WOS:000250388000012 PM 17947641 ER PT J AU Kannian, P Drouin, EE Glickstein, L Kwok, WW Nepom, GT Steere, AC AF Kannian, Priya Drouin, Elise E. Glickstein, Lisa Kwok, William W. Nepom, Gerald T. Steere, Allen C. TI Decline in the frequencies of Borrelia burgdorferi OspA(161-175)-Specific T cells after antibiotic therapy inHLA-DRB1*0401-positive patients with antibiotic-responsive or antibiotic-refractory Lyme arthritis SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CLASS-II TETRAMERS; SURFACE PROTEIN-A; HLA-DR MOLECULES; TREATMENT-RESISTANT; EX-VIVO; ASSOCIATION; DISEASE; HLA-DR4; FLUID; OSPA AB Synovitis in patients with antibiotic-refractory Lyme arthritis persists for months to several years after antibiotic therapy. This course, which may result from infection-induced autoimmunity, is associated- with T cell recognition of Borrelia burgdorferi outer surface protein A(OspA(161-175)) and with HLA-DR molecules that bind this epitope, including the DRB1*0401 molecule. In this study, we used tetramer reagents to determine the frequencies of OspA(161-175)-specific T cells in samples of PBMC and synovial fluid mommuclear cells (SFMC) from 13 DRB1*0401-positive patients with antibiotic- responsive or antibiotic-refractory arthritis. Initially, three of the six patients (50%) with antibiotic-responsive arthritis and four of the seven patients (57%) with antibioticrefractory arthritis had frequencies of OspA(161-175)-specific CD4(+) T cells in peripheral blood above the cutoff value of 4 per 105 cells. Among the five patients with concomitant PBMC and SFMC, four (80%) had OspA tetramer-positive cells at both sites, but the mean frequency of such cells was 16 times higher in SFMC, reaching levels as high as 1,177 per 105 cells. In the two patients in each patient group in whom serial samples were available, the frequencies of OspA(161-175)-specific T cells declined to low or undetectable levels during or soon after antibiotic therapy, months before the resolution of synovitis in the two patients with antibiotic-refractory arthritis. Thus, the majority of patients with Lyme arthritis initially have increased frequencies of OspA(161-175)-specific T cells. However, the marked decline in the frequency of such cells with antibiotic therapy suggests that persistent synovitis in the refractory group is not perpetuated by these cells. C1 Massachusetts Gen Hosp, Ctr Immunol & Infammatory Dis, Boston, MA 02114 USA. Univ Washington, Virginia Mason Med Ctr, Benaroya Res Inst, Seattle, WA 98101 USA. RP Steere, AC (reprint author), Massachusetts Gen Hosp, Ctr Immunol & Infammatory Dis, 55 Fruit St,Charlestown Navy Yard 149-8301, Boston, MA 02114 USA. EM asteere@partners.org OI Nepom, Gerald/0000-0002-8063-1464 NR 31 TC 12 Z9 12 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 1 PY 2007 VL 179 IS 9 BP 6336 EP 6342 PG 7 WC Immunology SC Immunology GA 223QS UT WOS:000250388000082 PM 17947711 ER PT J AU Lu, Q Wu, A Tesmer, L Ray, D Yousif, N Richardson, B AF Lu, Qianjin Wu, Ailing Tesmer, Laura Ray, Donna Yousif, Neda Richardson, Bruce TI Demethylation of CD40LG on the inactive X in T cells from women with lupus SO JOURNAL OF IMMUNOLOGY LA English DT Article ID DNA METHYLATION; CUTTING EDGE; ERYTHEMATOSUS; LIGAND; EXPRESSION; DISEASE; OVEREXPRESSION; LYMPHOCYTES; CHROMOSOME; INHIBITORS AB Why systemic lupus erythematosus primarily affects women is unknown. Recent evidence indicates that human lupus is an epigenetic disease characterized by impaired T cell DNA methylation. Women have two X chromosomes; one is inactivated by mechanisms including DNA methylation. We hypothesized that demethylation of sequences on the inactive X may cause gene overexpression uniquely in women, predisposing them to lupus. We therefore compared expression and methylation of CD40LG, a B cell costimulatory molecule encoded on the X chromosome, in experimentally demethylated T cells from men and women and in men and women with lupus. Controls included TNFSF7, a methylation-sensitive autosomal B cell costimulatory molecule known to be demethylated and overexpressed in lupus. Bisulfite sequencing revealed that CD40LG is unmethylated in men, while women have one methylated and one unmethylated gene. 5-Azacytidine, a DNA methyltransferase inhibitor, demethylated CD40LG and doubled its expression on CD4(+) T cells from women but not men, while increasing TNFSF7 expression equally between sexes. Similar studies demonstrated that CD40LG demethylates in CD4(+) T cells from women with lupus, and that women but not men with lupus overexpress CD40LG on CD4(+) T cells, while both overexpress TNFSF7. These studies demonstrate that regulatory sequences on the inactive X chromosome demethylate in T cells from women with lupus, contributing to CD40LG overexpression uniquely in women. Demethylation of CD40LG and perhaps other genes on the inactive X may contribute to the striking female predilection of this disease. C1 Univ Michigan, Dept Med, Ann Arbor, MI 48109 USA. Cent S Univ, Xiangya Hosp 2, Dept Dermatol, Changsha 41011, Hunan, Peoples R China. Massachusetts Gen Hosp, Dept Med Pediat, Boston, MA 02114 USA. Ann Arbor Vet Affairs Med Ctr, Dept Med, Ann Arbor, MI 48109 USA. RP Richardson, B (reprint author), Univ Michigan, Dept Med, 3007 Biomed Sci Res Bldg, Ann Arbor, MI 48109 USA. EM Brichard@umich.edu FU NIA NIH HHS [AG25877]; NIAMS NIH HHS [AR42525, P30AR048310]; NIEHS NIH HHS [ES015214, T32 ES007062] NR 30 TC 181 Z9 193 U1 1 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 1 PY 2007 VL 179 IS 9 BP 6352 EP 6358 PG 7 WC Immunology SC Immunology GA 223QS UT WOS:000250388000084 PM 17947713 ER PT J AU Lenahan, C Cho, D Bissonnette, A Chyu, C Signoretti, S Amato, A Goldberg, N Rosenblatt, J Schor-Bardach, R Vasir, D Wu, ZK Freeman, G Kufe, D Mier, JW Atkins, MB Avigan, D AF Lenahan, Corrine Cho, Daniel Bissonnette, Adam Chyu, Carolyn Signoretti, Sabina Amato, Angela Goldberg, Nahum Rosenblatt, Jacalyn Schor-Bardach, Rachel Vasir, David Wu, Zekui Freeman, Gordon Kufe, Donald Mier, James W. Atkins, Michael B. Avigan, David TI Immunologic effects of sunitinib in renal cell carcinoma SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 22nd Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY NOV 02-04, 2007 CL Boston, MA SP Int Soc Biol Therapy Canc C1 [Lenahan, Corrine; Cho, Daniel; Chyu, Carolyn; Goldberg, Nahum; Rosenblatt, Jacalyn; Schor-Bardach, Rachel; Mier, James W.; Atkins, Michael B.; Avigan, David] Beth Israel Deaconess Med Ctr, Boston, MA USA. [Bissonnette, Adam; Amato, Angela; Vasir, David; Wu, Zekui; Freeman, Gordon; Kufe, Donald] Dana Farber Canc Inst, Boston, MA USA. [Signoretti, Sabina] Brigham & Womens Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2007 VL 30 IS 8 BP 879 EP 879 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 223UB UT WOS:000250396700089 ER PT J AU Avigan, D Rosenblatt, J Vasir, B Atkins, MB McDermott, DF Lenahan, C Wu, Z Bissonnette, A MacNamara, C Levine, JD Uhl, L Fitzgerald, D Lowe, K Dombagoda, D Clancy, M Kufe, D AF Avigan, David Rosenblatt, Jacalyn Vasir, Baldev Atkins, Michael B. McDermott, David F. Lenahan, Corrine Wu, Zekui Bissonnette, Adam MacNamara, Claire Levine, James D. Uhl, Lynne Fitzgerald, Donna Lowe, Karen Dombagoda, Dilani Clancy, Myles Kufe, Donald TI Vaccination of patients with metastatic renal carcinoma with dendritic Cell/Tumor Fusions following debulking nephrectomy SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 22nd Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY NOV 02-04, 2007 CL Boston, MA SP Int Soc Biol Therapy Canc C1 [Avigan, David; Rosenblatt, Jacalyn; Atkins, Michael B.; McDermott, David F.; Lenahan, Corrine; MacNamara, Claire; Levine, James D.; Uhl, Lynne; Fitzgerald, Donna; Lowe, Karen; Dombagoda, Dilani; Clancy, Myles] Dana Farber Canc Inst, Boston, MA 02115 USA. [Vasir, Baldev; Wu, Zekui; Bissonnette, Adam; Kufe, Donald] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2007 VL 30 IS 8 BP 890 EP 891 PG 2 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 223UB UT WOS:000250396700127 ER PT J AU Rosenblatt, J Wu, ZK Lenahan, C Vasir, B Bissonnette, A Ghebremichael, M Kufe, D Avigan, D AF Rosenblatt, Jacalyn Wu, Zekui Lenahan, Corrine Vasir, Baldev Bissonnette, Adam Ghebremichael, Musie Kufe, Donald Avigan, David TI Adoptive immunotherapy using T cells stimulated by dendritic cell/tumor fusions and anti CD3/CD28 SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 22nd Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY NOV 02-04, 2007 CL Boston, MA SP Int Soc Biol Therapy Canc C1 [Rosenblatt, Jacalyn; Lenahan, Corrine; Avigan, David] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Wu, Zekui; Vasir, Baldev; Bissonnette, Adam; Ghebremichael, Musie; Kufe, Donald] Dana Farber Canc Inst, 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 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2007 VL 30 IS 8 BP 901 EP 901 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 223UB UT WOS:000250396700159 ER PT J AU Vasir, B Lenahan, C Bissonnette, A Rosenblatt, J Wu, ZK Kufe, D Avigan, D AF Vasir, Baldev Lenahan, Corrine Bissonnette, Adam Rosenblatt, Jacalyn Wu, Zekui Kufe, Donald Avigan, David TI Induction of anti-tumor immunity ex-vivo using dendritic cells transduced with fowl pox vector expressing MUC-1 and a triad of costimulatory molecules (PANVAC-F) SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 22nd Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY NOV 02-04, 2007 CL Boston, MA SP Int Soc Biol Therapy Canc C1 [Vasir, Baldev; Bissonnette, Adam; Wu, Zekui; Kufe, Donald] Dana Farber Canc Inst, Boston, MA 02115 USA. [Lenahan, Corrine; Rosenblatt, Jacalyn; Avigan, David] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2007 VL 30 IS 8 BP 903 EP 903 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 223UB UT WOS:000250396700166 ER PT J AU Hyle, EP Gasink, LB Linkin, DR Bilker, WB Lautenbach, E AF Hyle, Emily P. Gasink, Leanne B. Linkin, Darren R. Bilker, Warren B. Lautenbach, Ebbing TI Use of different thresholds of prior antimicrobial use in defining exposure: Impact on the association between antimicrobial use and antimicrobial resistance SO JOURNAL OF INFECTION LA English DT Article DE resistance; antimicrobial; FQRPA; fluoroquinolones; methodology ID RISK-FACTORS; KLEBSIELLA-PNEUMONIAE; LIMITATIONS; INFECTION AB Objectives: Although many studies have explored the association between antimicrobial use and antimicrobial resistance, definitions of "exposure" (i.e., prior antimicrobial use) differ across such studies. Specifically, it has been noted that some studies define "exposure" as any antimicrobial use, while others require the administration of at least 24 or 48 h of an antimicrobial to constitute "exposure." The impact of different definitions of exposure on final study results is unknown. We conducted the current study to determine the impact of varying the minimum threshold of prior antimicrobial use to define exposure status in studies of antimicrobial resistance. Methods: We used a dataset from a prior study of risk factors for fluoroquinolone (FQ) resistant Pseudomonas aeruginosa (FQRPA) to address the study aim. Four separate multivariable models of risk factors for FQRPA were built. Each model defined a different threshold for the duration of antimicrobial administration to determine "exposure" to that antimicrobial: (1) no threshold (i.e., a subject is considered exposed if any use of the antimicrobial was documented); (2) > 24 h of use of the antimicrobial is necessary to be considered exposed; (3) > 48 h of use is required; and (4) > 72 h of use is required. Except for these definitions, the four multivariable models were built in exactly the same way, each using prior FQ use as the primary risk factor of interest. Results: Among 872 P. aeruginosa isolates included in the original dataset, 332 (38.2%) were FQ-resistant. Each of the four multivariable models identified prior FQ use as an independent risk factor for FQRPA. However, as increasingly strict thresholds were used, the association between FQ use and FQRPA increased. Furthermore, prior use of an agent with activity against anaerobic bacteria was associated with FQRPA in models 2, 3 and 4, but not in model 1. Conclusions: The use of different thresholds to define prior "exposure" to antimicrobials altered the associations between antimicrobial use and resistance. Stricter thresholds resulted in a higher estimate of the association between antimicrobial use and resistance. Furthermore, different risk factors may be identified depending on how exposure is defined. Greater attention to this issue is necessary to optimize identification of modifiable risk factors for resistance as well as accurately compare results across studies. (c) 2007 Published by Elsevier Ltd on behalf of The British Infection Society. C1 Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Med, Div Infect Dis, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Ctr Educ & Res Therapeut, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Philadelphia, PA USA. RP Lautenbach, E (reprint author), Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, 825 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM ebbing@mail.med.upenn.edu OI Linkin, Darren R./0000-0002-2408-0987 FU NIAID NIH HHS [K23-AI-060887-01, T32 AI055435]; NIDDK NIH HHS [DK-02987-01] NR 16 TC 7 Z9 8 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0163-4453 J9 J INFECTION JI J. Infect. PD NOV PY 2007 VL 55 IS 5 BP 414 EP 418 DI 10.1016/j.jinf.2007.07.005 PG 5 WC Infectious Diseases SC Infectious Diseases GA 234KM UT WOS:000251160300005 PM 17850877 ER PT J AU Rutkute, K Asmis, RH Nikolova-Karakashian, MN AF Rutkute, Kristina Asmis, Reto H. Nikolova-Karakashian, Mariana N. TI Regulation of neutral sphingomyelinase-2 by GSH: a new insight to the role of oxidative stress in aging-associated inflammation SO JOURNAL OF LIPID RESEARCH LA English DT Article DE ceramide; calorie restriction; interleukin-1 receptor-associated kinase-1; c-Jun N-terminal kinase; reduced glutathione ID RECEPTOR-ASSOCIATED KINASE; CYTOCHROME-P450 2C11 CYP2C11; AGE-ASSOCIATED INCREASE; KAPPA-B ACTIVITY; ANTIOXIDANT ENZYMES; LIVER GLUTATHIONE; PLASMA-MEMBRANE; RAT HEPATOCYTES; CELL-DEATH; CERAMIDE AB Oxidative stress and inflammation are fundamental for the onset of aging and appear to be causatively linked. Previously, we reported that hepatocytes from aged rats, compared with young rats, are hyperresponsive to interleukin-1 beta (IL-1 beta) stimulation and exhibit more potent c-Jun N-terminal kinase ( JNK) activation and attenuated interleukin-1 receptor-associated kinase-1 ( IRAK-1) degradation. An age-related increase in the activity of neutral sphingomyelinase-2 ( NSMase-2), a plasma membrane enzyme, was found to be responsible for the IL-1 beta hyperresponsiveness. The results reported here show that increased NSMase activity during aging is caused by a 60-70% decrease in hepatocyte GSH levels. GSH, at concentrations typically found in hepatocytes from young animals, inhibits NSMase activity in a biphasic dose-dependent manner. Inhibition of GSH synthesis in young hepatocytes activates NSMase, causing increased JNK activation and IRAK-1 stabilization in response to IL-1 beta, mimicking the hyperresponsiveness typical for aged hepatocytes. Vice versa, increased GSH content in hepatocytes from aged animals by treatment with N-acetylcysteine inhibits NSMase activity and restores normal IL-1 beta response. Importantly, the GSH decline, NSMase activation, and IL-1 beta hyperresponsiveness are not observed in aged, calorie-restricted rats. In summary, this report demonstrates that depletion of cellular GSH during aging plays an important role in regulating the hepatic response to IL-1 beta by inducing NSMase-2 activity. C1 Univ Kentucky, Albert B Chandler Med Ctr, Dept Physiol, Lexington, KY 40536 USA. Univ Texas, Hlth Sci Ctr, Audie L Murphy Vet Hosp, Div Nephrol, San Antonio, TX 78284 USA. RP Nikolova-Karakashian, MN (reprint author), Univ Kentucky, Albert B Chandler Med Ctr, Dept Physiol, Lexington, KY 40536 USA. EM mnikolo@uky.edu FU NIA NIH HHS [R01 AG019223, R01 AG026711, R01 AG026711-01A2] NR 51 TC 33 Z9 34 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD NOV PY 2007 VL 48 IS 11 BP 2443 EP 2452 DI 10.1194/jlr.M700227-JLR200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 220HT UT WOS:000250148500012 PM 17693623 ER PT J AU Volandes, A AF Volandes, Angelo TI Medical ethics on film: Towards a reconstruction of the teaching of healthcare professionals SO JOURNAL OF MEDICAL ETHICS LA English DT Article AB The clinical vignette remains the standard means by which medical ethics are taught to students in the healthcare professions. Although written or verbal vignettes are useful as a pedagogic tool for teaching ethics and introducing students to real cases, they are limited, since students must imagine the clinical scenario. Medical ethics are almost universally taught during the early years of training, when students are unfamiliar with the clinical reality in which ethics issues arise. Film vignettes fill in that imaginative leap. By providing vivid details with images, film vignettes offer rich and textured details of cases, including the patient's perspective and the clinical reality. Film vignettes provide a detailed ethnography that allows for a more complete discussion of the ethical issues. Film can serve as an additional tool for teaching medical ethics to members of the healthcare professions. C1 Massachusetts Gen Hosp, Green Med Unit, Boston, MA 02114 USA. RP Volandes, A (reprint author), Massachusetts Gen Hosp, Green Med Unit, 50 Staniford St,9th Floor, Boston, MA 02114 USA. EM avolandes@partners.org NR 6 TC 14 Z9 14 U1 1 U2 2 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0306-6800 J9 J MED ETHICS JI J. Med. Ethics PD NOV PY 2007 VL 33 IS 11 BP 678 EP 680 DI 10.1136/jme.2006.017665 PG 3 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 225WF UT WOS:000250548200016 PM 17971475 ER PT J AU Wheeler, VC Persichetti, F McNeil, SM Mysore, JS Mysore, SS MacDonald, ME Myers, RH Gusella, JF Wexler, NS AF Wheeler, V. C. Persichetti, F. McNeil, S. M. Mysore, J. S. Mysore, S. S. MacDonald, M. E. Myers, R. H. Gusella, J. F. Wexler, N. S. CA US Venezuela Collaborat Grp TI Factors associated with HD CAG repeat instability in Huntington disease SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID AGE-OF-ONSET; TRINUCLEOTIDE REPEAT; TRANSGENIC MICE; SOMATIC INSTABILITY; ALLELE LENGTH; GENE; MUTATION; EXPANSION; SPERM; MOSAICISM AB Background: The Huntington disease (HD) CAG repeat exhibits dramatic instability when transmitted to subsequent generations. The instability of the HD disease allele in male intergenerational transmissions is reflected in the variability of the CAG repeat in DNA from the sperm of male carriers of the HD gene. Results: In this study, we used a collection of 112 sperm DNAs from male HD gene-positive members of a large Venezuelan cohort to investigate the factors associated with repeat instability. We confirm previous observations that CAG repeat length is the strongest predictor of repeat-length variability in sperm, but we did not find any correlation between CAG repeat instability and either age at the time of sperm donation or affectedness status. We also investigated transmission instability for 184 father - offspring and 311 mother - offspring pairs in this Venezuelan pedigree. Repeat-length changes were dependent upon the sex of the transmitting parent and parental CAG repeat length but not parental age or birth order. Unexpectedly, in maternal transmissions, repeat-length changes were also dependent upon the sex of the offspring, with a tendency for expansion in male offspring and contraction in female offspring. Conclusion: Significant sibling - sibling correlation for repeat instability suggests that genetic factors play a role in intergenerational CAG repeat instability. C1 Massachusetts Gen Hosp, Mol Neurogenet Unit, Ctr Human Genet Res, Boston, MA 02114 USA. Scuola Int Super Studi Avanzati, Trieste, Italy. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. Columbia Univ, New York, NY USA. RP Wheeler, VC (reprint author), Massachusetts Gen Hosp, Mol Neurogenet Unit, Ctr Human Genet Res, Richard B Simches Res Bldg 5808,185 Cambridge St, Boston, MA 02114 USA. EM wheeler@helix.mgh OI Myers, Richard/0000-0002-8365-2674 FU NINDS NIH HHS [P50 NS016367-28, NS049206, P50 NS016367, R01 NS049206, R01 NS049206-04] NR 33 TC 46 Z9 46 U1 0 U2 7 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD NOV PY 2007 VL 44 IS 11 BP 695 EP 701 DI 10.1136/jmg.2007.050930 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 226VM UT WOS:000250616600003 PM 17660463 ER PT J AU Masciari, S Larsson, N Senz, J Boyd, N Kaurah, P Kandel, MJ Harris, LN Pinheiro, HC Troussard, A Miron, P Tung, N Oliveira, C Collins, L Schnitt, S Garber, JE Huntsman, D AF Masciari, S. Larsson, N. Senz, J. Boyd, N. Kaurah, P. Kandel, M. J. Harris, L. N. Pinheiro, H. C. Troussard, A. Miron, P. Tung, N. Oliveira, C. Collins, L. Schnitt, S. Garber, J. E. Huntsman, D. TI Germline E-cadherin mutations in familial lobular breast cancer SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID DIFFUSE GASTRIC-CANCER; CDH1 MUTATIONS; CELL-ADHESION; GENE; CARCINOMA; PROMOTER; TUMOR; METHYLATION; EXPRESSION; MANAGEMENT AB Background: The cell surface glycoprotein E-cadherin (CDH1) is a key regulator of adhesive properties in epithelial cells. Germline mutations in CDH1 are well established as the defects underlying hereditary diffuse gastric cancer (HDGC) syndrome, and an increased risk of lobular breast cancer (LBC) has been described in HDGC kindreds. However, germline CDH1 mutations have not been described in patients with LBC in non-HDGC families. This study aimed to investigate the frequency of germline CDH1 mutations in patients with LBC with early onset disease or family histories of breast cancer without DGC. Methods: Germline DNA was analysed in 23 women with invasive lobular or mixed ductal and lobular breast cancers who had at least one close relative with breast cancer or had themselves been diagnosed before the age of 45 years, had tested negative for a germline BRCA1 or BRCA2 mutation, and reported no personal or family history of diffuse gastric cancer. The full coding sequence of CDH1 including splice junctions was amplified using PCR and screened for mutations using DHPLC and sequencing. Results: A novel germline CDH1 truncating mutation in the extracellular portion of the protein (517insA) was identified in one woman who had LBC at the age of 42 years and a first degree relative with invasive LBC. Conclusions: Germline CDH1 mutations can be associated with invasive LBC in the absence of diffuse gastric cancer. The finding, if confirmed, may have implications for management of individuals at risk for this breast cancer subtype. Clarification of the cancer risks in the syndrome is essential. C1 British Columbia Canc Agcy, Hereditary Canc Program, Vancouver, BC V5Z 4E6, Canada. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Univ Lund Hosp, Dept Clin Genet, S-22185 Lund, Sweden. Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC V5Z 1M9, Canada. Univ Hosp Schleswig Holstein, Dept Obstet & Gynecol, Campus Kiel, Germany. Yale Canc Ctr, New Haven, CT USA. Univ Porto, IPAIMUP, Inst Mol Pathol & Immunol, P-4100 Oporto, Portugal. Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Dept Med Oncol, Boston, MA 02215 USA. Univ Porto, Fac Med, P-4100 Oporto, Portugal. Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA. RP Huntsman, D (reprint author), British Columbia Canc Agcy, Hereditary Canc Program, 600 West 10th Ave,Room 3427, Vancouver, BC V5Z 4E6, Canada. EM dhuntsma@bccancer.bc.ca RI Oliveira, Carla/F-8188-2011; Pinheiro, Hugo/C-7099-2013 OI Oliveira, Carla/0000-0001-8340-2264; Pinheiro, Hugo/0000-0001-5329-8224 NR 30 TC 81 Z9 83 U1 3 U2 8 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD NOV PY 2007 VL 44 IS 11 BP 726 EP 731 DI 10.1136/jmg.2007.051268 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 226VM UT WOS:000250616600008 PM 17660459 ER PT J AU Ota, H Akishita, M Masato, E Iijima, K Masao, K Ouchi, Y AF Ota, Hidetaka Akishita, Masahiro Eto, Masato Iijima, Katsuya Kaneki, Masao Ouchi, Yasuyoshi TI Sirt1 modulates premature senescence-like phenotype in human endothelial cells SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Article DE sirt1; sirtinol; premature senescence; endothelial dysfunction; oxidative stress ID NORMAL HUMAN FIBROBLASTS; REPLICATIVE SENESCENCE; CELLULAR SENESCENCE; NITRIC-OXIDE; SACCHAROMYCES-CEREVISIAE; DEPENDENT REGULATION; GROWTH ARREST; LIFE-SPAN; P53; APOPTOSIS AB Yeast Sir2 plays critical roles in gene silencing, stress resistance and longevity. Mammalian Sirt1 NAD(+)-dependent protein deacetylase, the closest homolog of Sir2, regulates cell cycle, cellular senescence, apoptosis and metabolism, by functional interactions with a number of biological molecules such as p53. To investigate a role of Sirt1 in endothelial dysfunction and premature senescence, we examined the effects of Sirt1 inhibition in human umbilical vein endothelial cells (HUVEC). Sirt1 inhibition by sirtinol, which is a 2-hydroxy-1-napthaldehyde derivative, or siRNA for Sirt1-induced premature senescence-like phenotype, as judged by increased senescence-associated beta-galactosidase (SA-beta-gal) activity, sustained growth arrest and enlarged and flattened cell morphology at 10 days after the treatment. Sixty-four percent of sirtinol (60 mu mol/L)treated HUVEC was SA-beta-gal-positive, whereas only 17% of vehicle-treated cells were positive. Sirt1 inhibition by sirtinol or Sirt1 siRNA increased PAI-1 expression and decreased both protein expression and activity of eNOS. Treatment with sirtinol or Sirt1 siRNA increased acetylation of p53, while p53 expression was unaltered. Impaired epidermal growth factor-induced activation of mitogen-activated protein kinases was associated with Sirt1 inhibition-induced senescence-like growth arrest. Conversely, overexpression of Sirt1 prevented hydrogen peroxideinduced SA-beta-gal activity, morphological changes and deranged expression of PAI-1 and eNOS. These results showed that Sirt1 inhibition increased p53 acetylation and induced premature senescence-like phenotype in parallel with increased PAI-1 and decreased eNOS expression. Our data suggest that Sirt1 may exert protective effects against endothelial dysfunction by preventing stress-induced premature senescence and deranged expression of PAI-1 and eNOS. (c) 2007 Elsevier Inc. All rights reserved. C1 Univ Tokyo, Grad Sch Med, Dept Geriatr Med, Bunkyo Ku, Tokyo 1138655, Japan. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Anesthesia & Crit Care, Charlestown, MA 02129 USA. RP Akishita, M (reprint author), Univ Tokyo, Grad Sch Med, Dept Geriatr Med, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1138655, Japan. EM akishita-tky@umin.acjp NR 42 TC 209 Z9 217 U1 1 U2 12 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD NOV PY 2007 VL 43 IS 5 BP 571 EP 579 DI 10.1016/j.yjincc.2007.08.008 PG 9 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 234KA UT WOS:000251158900007 PM 17916362 ER PT J AU Wu, D Vu, Q Sholl, LM Lafrate, AJ AF Wu, D. Vu, Q. Sholl, L. M. Lafrate, A. J. TI FISH-based in situ chimerism analysis: A proof-of-principle study utilizing probes from large-scale copy number variant loci SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Meeting Abstract CT 13th Annual Meeting of the Association-for-Molecular-Pathology CY NOV 07-10, 2007 CL Los Angeles, CA SP Assoc Mol Pathol C1 [Wu, D.; Vu, Q.; Sholl, L. M.; Lafrate, A. J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 1525-1578 J9 J MOL DIAGN JI J. Mol. Diagn. PD NOV PY 2007 VL 9 IS 5 BP 650 EP 651 PG 2 WC Pathology SC Pathology GA 230BC UT WOS:000250849300018 ER PT J AU Louissaint, A Batten, JM Kradin, R Iafrate, AJ AF Louissaint, A. Batten, J. M. Kradin, R. Iafrate, A. J. TI Molecular identification and subtyping of mycobacterium from formalin-fixed, paraffin-embedded tissue SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Meeting Abstract CT 13th Annual Meeting of the Association-for-Molecular-Pathology CY NOV 07-10, 2007 CL Los Angeles, CA SP Assoc Mol Pathol C1 [Louissaint, A.; Batten, J. M.; Kradin, R.; Iafrate, A. J.] Massachusetts Gen Hosp, Pathol Serv, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 1525-1578 J9 J MOL DIAGN JI J. Mol. Diagn. PD NOV PY 2007 VL 9 IS 5 BP 683 EP 683 PG 1 WC Pathology SC Pathology GA 230BC UT WOS:000250849300159 ER PT J AU Sholf, LM Janne, PA Jackman, DM Joshi, VA Lindeman, NI AF Sholf, L. M. Janne, P. A. Jackman, D. M. Joshi, V. A. Lindeman, N. I. TI EGFR kinase domain mutations, but not copy number, predict response to erlotinib and gefitinib in patients with advanced lung adenocarcinoma SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Meeting Abstract CT 13th Annual Meeting of the Association-for-Molecular-Pathology CY NOV 07-10, 2007 CL Los Angeles, CA SP Assoc Mol Pathol C1 [Sholf, L. M.; Lindeman, N. I.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Sholf, L. M.; Janne, P. A.; Jackman, D. M.; Joshi, V. A.; Lindeman, N. I.] Harvard Med Sch, Boston, MA USA. [Janne, P. A.; Jackman, D. M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Joshi, V. A.] Harvard Partners Ctr Genet & Genom, Mol Med Lab, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 1525-1578 J9 J MOL DIAGN JI J. Mol. Diagn. PD NOV PY 2007 VL 9 IS 5 BP 692 EP 692 PG 1 WC Pathology SC Pathology GA 230BC UT WOS:000250849300197 ER PT J AU Shahidi, A Montalvan, I Perozo, I Fernandes, H AF Shahidi, A. Montalvan, I. Perozo, I. Fernandes, H. TI Comparison of invader and LIPA in the determination of hepatitis C virus genotype using COBAS TaqMan amplicons SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Meeting Abstract CT 13th Annual Meeting of the Association-for-Molecular-Pathology CY NOV 07-10, 2007 CL Los Angeles, CA SP Assoc Mol Pathol C1 [Shahidi, A.; Perozo, I.] James J Peters Vet Affairs Med Ctr, Bronx, NY USA. [Montalvan, I.] Univ Med & Dent New Jersey, Sch Med, Newark, NJ 07103 USA. [Fernandes, H.] Univ Med & Dent New Jersey, Newark, NJ 07103 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 1525-1578 J9 J MOL DIAGN JI J. Mol. Diagn. PD NOV PY 2007 VL 9 IS 5 BP 697 EP 698 PG 2 WC Pathology SC Pathology GA 230BC UT WOS:000250849300221 ER PT J AU Barnholtz-Sloan, JS Maldonado, JL Williams, VL Curry, WT Rodkey, EA Barker, FG Sloan, AE AF Barnholtz-Sloan, Jill S. Maldonado, John L. Williams, Vonetta L. Curry, William T. Rodkey, Elizabeth A. Barker, Frederick G., II Sloan, Andrew E. TI Racial/ethnic differences in survival among elderly patients with a primary glioblastoma SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE elderly; glioblastoma; race/ethnicity; SEER-medicare; survival ID MALIGNANT BRAIN-TUMORS; NERVOUS-SYSTEM TUMORS; ETHNIC DISTRIBUTION; RACIAL-DIFFERENCES; UNITED-STATES; RECENT TRENDS; GLIOMAS; RADIOTHERAPY; DIAGNOSIS; PATTERNS AB Background Few studies have assessed racial/ethnic differences in survival after primary glioblastoma diagnosis. We investigate these differences, incorporating information on White, Hispanics and Asians, as well as White, non-Hispanics and Blacks, among elderly individuals with a primary glioblastoma utilizing the population-based Surveillance, Epidemiology and End Results (SEER) Program-Medicare linked database. Methods A total of 1,530 individuals diagnosed > = 66 years of age from 6/1/91 to 12/31/99 in the SEER data were linked with Medicare information from 1/1/91 to 12/31/01. All individuals had Medicare Parts A and B and were non-HMO for 6 months before and 12 months after diagnosis to gather pre-diagnosis co-morbidities and post-diagnosis first course of treatment. Survival differences by race/ethnicity and by race/ethnicity stratified by treatment type and/or median household income were examined using Kaplan-Meier and multivariable Cox proportional hazards models. Results Significant racial/ethnic differences existed between White, non-Hispanics and Blacks in marital status, income and SEER registry region for the entire US. In analysis limited to the West region, significant racial/ethnic differences existed for income only. Overall there were no differences in survival between White, non-Hispanics and Blacks, however, in analysis limited to the West region, Asians had a lower risk of death compared to White, non-Hispanics [HR = 0.67, 95% CI (0.43, 1.03)]. Asians who had multiple treatments also had a lower risk of death compared to White, non-Hispanics [HR = 0.65, 95% CI (0.41, 1.01)]. Conclusion Racial/ethnic differences in survival after primary glioblastoma diagnosis exist and may be partially explained by racial/ethnic differences in treatment and income. C1 Case Western Reserve Univ, Case Comprehens Canc Ctr, Sch Med, Cleveland, OH 44106 USA. H Lee Moffitt Canc Ctr & Res Inst, Res Inst, Tampa, FL USA. Univ S Florida, Coll Publ Hlth, Dept Epidemiol & Biostat, Tampa, FL USA. Massachusetts Gen Hosp, Harvard Med Sch, Dept Neurosurg, Boston, MA 02114 USA. RP Barnholtz-Sloan, JS (reprint author), Case Western Reserve Univ, Case Comprehens Canc Ctr, Sch Med, 111000 Euclid Ave, Cleveland, OH 44106 USA. EM jsb42@case.edu; john.maldonado@moffitt.org; vonetta.williams@moffitt.org; wcurry@partners.org; elizabeth.rodkey@moffitt.org; barker@helix.mgh.harvard.edu; Andrew.Sloan@uhhospitals.org RI Barnholtz-Sloan, Jill/A-4817-2011 FU NCI NIH HHS [K07 CA91849]; PHS HHS [K08101954] NR 50 TC 28 Z9 28 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-594X J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD NOV PY 2007 VL 85 IS 2 BP 171 EP 180 DI 10.1007/s11060-007-9405-4 PG 10 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 222NH UT WOS:000250303700006 PM 17530174 ER PT J AU Won, JS Singh, AK Singh, I AF Won, Je-Seong Singh, Avtar K. Singh, Inderjit TI Lactosylceramide: a lipid second messenger in neuroinflammatory disease SO JOURNAL OF NEUROCHEMISTRY LA English DT Article; Proceedings Paper CT 2nd ISN Special Neurochemistry Conference CY DEC 01-05, 2006 CL ANTIGUA & BARBU SP Int Soc Neurochem DE glucosylceramide : UDPgaltransferase (beta 4GalTVI); lactosylceramide; mitogen-activated protein kinases; NF kappa B; PI3Kinase; Ras GTPase; sphingomyelinase ID NITRIC-OXIDE SYNTHASE; TUMOR-NECROSIS-FACTOR; RICH MEMBRANE RAFTS; NEUTRAL SPHINGOMYELINASE ACTIVATION; RAT PRIMARY ASTROCYTES; NIEMANN-PICK DISEASE; NF-KAPPA-B; ACID SPHINGOMYELINASE; NADPH OXIDASE; GLYCOSPHINGOLIPID BIOSYNTHESIS AB Inflammatory disease plays a critical role in the pathogenesis of many neurological disorders. Astrogliosis and induction of pro-inflammatory mediators such as chemokines, cytokines and inducible nitric oxide synthase (iNOS) are the 'hallmarks' of inflammatory disease. Increased activity of lactosylceramide (LacCer) synthase and increased synthesis of LacCer during glial proliferation, and induction of pro-inflammatory cytokines and iNOS suggests a role for LacCer in these cellular signaling pathways. Studies using complementary techniques of inhibitors and antisense reported that inhibition of LacCer synthesis inhibits glial proliferation, as well as the induction of pro-inflammatory mediators (cytokines and iNOS). This inhibition was bypassed by exogenous LacCer, but not by other related lipids (e.g. glucosylceramide, galactocerebroside, GD1, GM1), indicating a role for LacCer in inflammatory signaling pathways. Furthermore, inhibition of glial proliferation and induction of inflammatory mediators by antisense to Ras GTPase, PI3Kinase and inhibitors of mitogen-activated protein kinase indicate the participation of the phosphoinositide 3-kinase (PI3Kinas)/Ras/mitogen-activated protein kinase/nuclear factor-kappa B (NF-kappa B) signaling pathways in LacCer-mediated inflammatory events thus exposing additional targets for therapeutics for inflammatory disease conditions. C1 Med Univ S Carolina, Charles P Darby Childrens Res Inst, Dept Pediat, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Pathol & Lab Med, Charleston, SC 29425 USA. Ralph H Johnson Vet Adm Med Ctr, Lab Med Serv, Charleston, SC USA. RP Singh, I (reprint author), Childrens Res Inst, Dept Pediat, 173 Ashley Ave, Charleston, SC 29425 USA. EM singhi@musc.edu FU NIA NIH HHS [AG25307]; NINDS NIH HHS [NS-34741, NS-22576, NS-37766] NR 124 TC 14 Z9 14 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3042 EI 1471-4159 J9 J NEUROCHEM JI J. Neurochem. PD NOV PY 2007 VL 103 SU 1 BP 180 EP 191 DI 10.1111/j.1471-4159.2007.04822.x PG 12 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 225XU UT WOS:000250552400022 PM 17986153 ER PT J AU Conrad, C Zhu, J Conrad, C Schoenfeld, D Fang, Z Ingelsson, M Stamm, S Church, G Hyman, BT AF Conrad, Chris Zhu, Jun Conrad, Cintia Schoenfeld, David Fang, Zhide Ingelsson, Martin Stamm, Stefan Church, George Hyman, Bradley T. TI Single molecule profiling of tau gene expression in Alzheimer's disease SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE Alzheimer's disease; splicing; tau ID PROGRESSIVE SUPRANUCLEAR PALSY; PRE-MESSENGER-RNA; ARGYROPHILIC GRAIN DISEASE; PROTEIN-TAU; MAPT LOCUS; SPORADIC TAUOPATHIES; HUMAN-BRAIN; EXON 10; HAPLOTYPE; ISOFORMS AB Tau is a microtubule-associated protein that is important for establishing and maintaining neuronal morphology. In addition to its role in normal cells, tau protein is involved in many neurodegenerative diseases, e.g. Alzheimer's disease (AD) and frontotemporal dementia, as the main component of intraneuronal aggregates. Alternative splicing of tau gene in the brain can give rise to at least six protein variants. A causative role of skewed tau exon 10 inclusion has been defined in frontotemporal dementia; however, no link was established between the aberrant splicing of tau and AD. Here, we applied a single-molecule-based technology, polymerase colony or polony, to simultaneously monitor tau splicing variant and haplotype profile in sporadic AD and normal brains. We found that the coordinated expression of tau exons 2 and 10 is altered in AD. Additional investigations of cis and trans mechanisms of this observation revealed a decreased protein expression of a known tau splicing factor, htra2-beta-1 in AD, thereby implicating a trans mechanism. Our results demonstrate that dysregulation of combinatorial splicing might serve as a signature for aging-related diseases, and the polony assay could be widely adapted for the study of other tauopathies. Furthermore, splicing-based therapeutics is an emerging area of drug development, and a well-defined and quantitative assay for monitoring single-gene transcriptome will be relevant for such development. C1 Mass Gen Inst Neurodegenerat Dis, Dept Neurol, Charlestown, MA USA. Duke Univ, Inst Genome Sci & Policy, Med Ctr, Durham, NC USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Univ New Orleans, Dept Math, New Orleans, LA 70148 USA. Univ Erlangen Nurnberg, Inst Biochem, Erlangen, Germany. Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. RP Zhu, J (reprint author), Columbia Univ, Taub Inst Res Alzheimers Dis & Aging Brain, Dept Pathol, 1150 St Nicholas Ave,Rm 527, New York, NY 10032 USA. EM jun.zhu@duke.edu FU NIA NIH HHS [P50AG005134] NR 48 TC 35 Z9 35 U1 1 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD NOV PY 2007 VL 103 IS 3 BP 1228 EP 1236 DI 10.1111/j.1471-4159.2007.04857.x PG 9 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 221ZS UT WOS:000250266500034 PM 17727636 ER PT J AU Ma, QL Harris-White, ME Ubeda, OJ Simmons, M Beech, W Lim, GP Teter, B Frautschy, SA Cole, GM AF Ma, Qiu-Lan Harris-White, Marni E. Ubeda, Oliver J. Simmons, Mychica Beech, Walter Lim, Giselle P. Teter, Bruce Frautschy, Sally A. Cole, Greg M. TI Evidence of A beta- and transgene-dependent defects in ERK-CREB signaling in Alzheimer's models SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE alzheimer disease; cAMP-response element-binding protein; extracellular-signal regulated kinase; immunization; signal transduction; Tg2576 mice ID ACTIVATED PROTEIN-KINASE; LONG-TERM POTENTIATION; GROWTH-FACTOR-I; AMYLOID-BETA; MOUSE MODEL; NMDA RECEPTOR; HIPPOCAMPAL-NEURONS; NEUROTROPHIC FACTOR; CORTICAL-NEURONS; UP-REGULATION AB Extracellular-signal regulated kinase (ERK) signaling is critical for memory and tightly regulated by acute environmental stimuli. In Alzheimer disease transgenic models, active ERK is shown to first be increased, then later reduced, but whether these baseline changes reflect disruptions in ERK signaling is less clear. We investigated the influence of the familial Alzheimer's disease transgene APPsw and beta-amyloid peptide (Ab) immunoneutralization on cannulation injury-associated (i. c. v. infusion) ERK activation. At both 12 and 22 months of age, the trauma-associated activation of ERK observed in Tg(-)) mice was dramatically attenuated in Tg(+). In cortices of 22-month-old non-infused mice, a reduction in ERK activation was observed in Tg+, relative to Tg(-)) mice. Intracerebroventricular (i. c. v.) anti-Ab infusion significantly increased phosphorylated ERK, its substrate cAMP-response element-binding protein (CREB) and a downstream target, the NMDA receptor subunit. We also demonstrated that Ab oligomer decreased active ERK and subsequently active CREB in human neuroblastoma cells, which could be prevented by oligomer immunoneutralization. Ab oligomers also inhibited active ERK and CREB in primary neurons, in addition to reducing the downstream post- synaptic protein NMDA receptor subunit. These effects were reversed by anti- oligomer. Our data strongly support the existence of an APPsw transgene- dependent and Ab oligomer- mediated defect in regulation of ERK activation. C1 Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. Greater Los Angeles Vet Affairs Healthcare Syst, VA Med Ctr, Geriatr Res & Clin Ctr, North Hills, CA 91343 USA. RP Ma, QL (reprint author), Greater Los Angeles Vet Affairs Healthcare Syst, Alzheimers Res, 151,Bldg 7,Room A101,16111 Plummer St, North Hills, CA 91343 USA. FU NIA NIH HHS [AG021975, AG022080, R01 AG010685, R01 AG010685-09, R01 AG010685-10, R01 AG010685-11, R01 AG010685-12, R01 AG010685-13, R01 AG010685-14, R01 AG016793, R01 AG016793-03, R01 AG016793-04, R01 AG016793-05, R01 AG021975, R01 AG021975-01A2, R01 AG021975-02, R01 AG021975-03, R01 AG021975-04, R01 AG022080]; NINDS NIH HHS [NS43946, R01 NS043946, R01 NS043946-01, R01 NS043946-02, R01 NS043946-03, R01 NS043946-04, R01 NS043946-05] NR 64 TC 63 Z9 65 U1 1 U2 7 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD NOV PY 2007 VL 103 IS 4 BP 1594 EP 1607 DI 10.1111/j.1471-4159.2007.04869.x PG 14 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 223WH UT WOS:000250403500030 PM 17760871 ER PT J AU Ingster-Moati, I Quoc, EB Pless, M Djomby, R Orssaud, C Guichard, JP Woimant, F AF Ingster-Moati, I. Quoc, E. Bui Pless, M. Djomby, R. Orssaud, C. Guichard, J. P. Woimant, F. TI Ocular motility and Wilson's disease: a study on 34 patients SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Article ID POSITRON EMISSION TOMOGRAPHY; BRAIN MRI; ABNORMALITIES; ACCOMMODATION; MITOCHONDRIA AB Background: Wilson's disease is an autosomal recessive genetic disorder resulting from an abnormality of copper metabolism. The excessive accumulation of copper in the brain induces an extrapyramidal syndrome. Oculomotor abnormalities occur in most extrapyramidal disorders but have rarely been studied in Wilson's disease. Objective: To evaluate the ocular motility manifestations of Wilson's disease. Methods: A prospective study of 34 patients affected by Wilson's disease who were recruited and their ocular motility recorded by electro-oculography (EOG). Results: Vertical smooth pursuit was abnormal in 29 patients (85%). Vertical optokinetic nystagmus and horizontal smooth pursuit were impaired in 41% and 41% of patients, respectively. No MRI abnormality was found in the lenticular nuclei of seven patients who manifested ocular motility abnormalities. Conclusion: Vertical eye movements, in particular vertical pursuits, are impaired in Wilson's disease, more often than vertical optokinetic nystagmus and vertical saccades. EOG abnormalities can be found in patients who do not yet exhibit anatomical lesions on MRI. C1 Univ Paris 07, Dept Ophthalmol, Hop Necker Enfants Malad, AP HP,INSERM,U669, Paris, France. Hop Lariboisiere, Assistance Publ Hop Paris 2, Serv Neurol, F-75475 Paris, France. Massachusetts Gen Hosp, Boston, MA 02114 USA. Hop Lariboisiere, Serv Neuroradiol, Assistance Publ Hop Paris 2, F-75475 Paris, France. RP Ingster-Moati, I (reprint author), Hop Necker Enfants Malad, Serv Ophthalmol, AP HP, 149 Rue Sevres, F-75015 Paris, France. EM isabelle.ingster-moati@nck.aphp.fr NR 21 TC 9 Z9 9 U1 0 U2 2 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-3050 J9 J NEUROL NEUROSUR PS JI J. Neurol. Neurosurg. Psychiatry PD NOV PY 2007 VL 78 IS 11 BP 1199 EP 1201 DI 10.1136/jnnp.2006.108415 PG 3 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA 225LE UT WOS:000250518600011 PM 17470473 ER PT J AU Hellier, JL Grosshans, DR Coultrap, SJ Jones, JP Dobelis, P Browning, MD Staley, KJ AF Hellier, Jennifer L. Grosshans, David R. Coultrap, Steven J. Jones, Jethro P. Dobelis, Peter Browning, Michael D. Staley, Kevin J. TI NMDA receptor trafficking at recurrent synapses stabilizes the state of the CA3 network SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID LONG-TERM POTENTIATION; D-ASPARTATE RECEPTOR; CULTURED HIPPOCAMPAL-NEURONS; SURFACE EXPRESSION; RAT HIPPOCAMPUS; IN-VITRO; COLLATERAL SYNAPSES; INVITRO MODEL; DEPRESSION; LTD AB Metaplasticity describes the stabilization of synaptic strength such that strong synapses are likely to remain strong while weak synapses are likely to remain weak. A potential mechanism for metaplasticity is a correlated change in both N-methyl-D-aspartate (NMDA) receptor-mediated postsynaptic conductance and synaptic strength. Synchronous activation of CA3-CA3 synapses during spontaneous bursts of population activity caused long-term potentiation (LTP) of recurrent CA3-CA3 glutamatergic synapses under control conditions and depotentiation when NMDA receptors were partially blocked by competitive antagonists. LTP was associated with a significant increase in membrane-bound NMDA receptors, whereas depotentiation was associated with a significant decrease in membrane-bound NMDA receptors. During burst activity, further depotentiation could be induced by sequential reductions in antagonist concentration, consistent with a depotentiation-associated reduction in membrane-bound NMDA receptors. The decrease in number of membrane-bound NMDA receptors associated with depotentiation reduced the probability of subsequent potentiation of weakened synapses in the face of ongoing synchronous network activity. This molecular mechanism stabilizes synaptic strength, which in turn stabilizes the state of the CA3 neuronal network, reflected in the frequency of spontaneous population bursts. C1 Univ Colorado, Hlth Sci Ctr, Dept Pediat & Neurol, Denver, CO 80202 USA. Univ Colorado, Hlth Sci Ctr, Dept Pharmacol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Program Neurosci, Denver, CO 80262 USA. RP Staley, KJ (reprint author), Massachusetts Gen Hosp, Dept Neurol, 114 16th St,B114-2625, Cambridge, MA 02129 USA. EM KStaley@partners.org NR 49 TC 8 Z9 8 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD NOV PY 2007 VL 98 IS 5 BP 2818 EP 2826 DI 10.1152/jn.00346.2007 PG 9 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 230UB UT WOS:000250900300029 PM 17728388 ER PT J AU Jho, HD Jho, DH AF Jho, Hae-Dong Jho, David H. TI Ventral uncoforaminotomy SO JOURNAL OF NEUROSURGERY-SPINE LA English DT Editorial Material ID ANTERIOR CERVICAL FORAMINOTOMY; TECHNICAL NOTE; DECOMPRESSION; MYELOPATHY C1 Drexel Univ, Coll Med, Allegheny Gen Hos,Dept Neuroendoscopy, Jho Inst Minimally Invas Neurosurg, Pittsburgh, PA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA USA. RP Jho, HD (reprint author), Drexel Univ, Coll Med, Allegheny Gen Hos,Dept Neuroendoscopy, Jho Inst Minimally Invas Neurosurg, Pittsburgh, PA USA. NR 15 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 1547-5654 J9 J NEUROSURG-SPINE JI J. Neurosurg.-Spine PD NOV PY 2007 VL 7 IS 5 BP 533 EP 535 PG 3 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 230LQ UT WOS:000250878400012 PM 17977195 ER PT J AU Schroeder, T Melo, MFV Musch, G Harris, RS Venegas, JG Winkler, T AF Schroeder, Tobias Melo, Marcos F. Vidal Musch, Guido Harris, R. Scott Venegas, Jose G. Winkler, Tilo TI Image-derived input function for assessment of F-18-FDG uptake by the inflamed lung SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE PET; Massachusetts General Hospital; F-18-FDG; acute lung injury; inflammation ID POSITRON-EMISSION-TOMOGRAPHY; BRAIN TRANSFER CONSTANTS; TIME UPTAKE DATA; GLUCOSE-UTILIZATION; NONINVASIVE QUANTIFICATION; GRAPHICAL EVALUATION; METABOLIC-ACTIVITY; PET; INJURY; DEOXYGLUCOSE AB Pulmonary uptake of F-18-FDG assessed with PET has been used to quantify the metabolic activity of inflammatory cells in the lung. This assessment involves modeling of tracer kinetics and knowledge of a time-activity curve in pulmonary artery plasma as an input function, usually acquired by manual blood sampling. This paper presents and validates a method to accurately derive an input function from a blood-pool region of interest (ROI) defined in dynamic PET images. Methods: The method is based on a 2-parameter model describing the activity of blood and that from spillover into the time-activity curve for the ROL The model parameters are determined using an iterative algorithm, with 2 blood samples used to calibrate the raw PET-derived activity data. We validated both the 2-parameter model and the method to derive a quantitative input function from ROIs defined for the cavities of the right and left heart and for the descending aorta by comparing them against the time-activity curve obtained by manual blood sampling from the pulmonary artery in lungs with acute inflammation. Results: The model accurately described the time-activity curve from sampled blood. The 2-sample calibration method provided an efficient algorithm to derive input functions that were virtually identical to those sampled manually, including the fast kinetics of the early phase. The F-18-FDG uptake rates in acutely injured lungs obtained using this method correlated well with those obtained exclusively using manual blood sampling (R-2 > 0.993). Within some bounds, the model was found quite insensitive to the timing of calibration blood samples or the exact definition of the blood-pool ROIs. Conclusion: Using 2 mixed venous blood samples, the method accurately assesses the entire time course of the pulmonary F-18-FDG input function and does not require the precise geometry of a specific blood-pool ROI or a population-based input function. This method may substantially facilitate studies involving modeling of pulmonary F-18-FDG in patients with viral or bacterial infections, pulmonary fibrosis, and chronic obstructive pulmonary disease. C1 [Schroeder, Tobias; Melo, Marcos F. Vidal; Musch, Guido; Venegas, Jose G.; Winkler, Tilo] Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. [Schroeder, Tobias; Melo, Marcos F. Vidal; Musch, Guido; Harris, R. Scott; Venegas, Jose G.; Winkler, Tilo] Harvard Univ, Sch Med, Boston, MA USA. [Harris, R. Scott] Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Boston, MA 02114 USA. RP Schroeder, T (reprint author), Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, 55 Fruit St, Boston, MA 02114 USA. EM tschroder@partners.org RI Winkler, Tilo/B-5337-2009; OI Winkler, Tilo/0000-0002-7276-5550; Schroeder, Tobias/0000-0002-4439-8060 FU NHLBI NIH HHS [HL068011, R01 HL068011, R01 HL086827, K08 HL076464, HL076464, R01 HL086827-01, HL056879] NR 25 TC 23 Z9 23 U1 1 U2 2 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD NOV PY 2007 VL 48 IS 11 BP 1889 EP 1896 DI 10.2967/jnumed.107.041079 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 258UL UT WOS:000252894900027 PM 17942803 ER PT J AU Conley, SB Branowicki, P Hanley, D AF Conley, Susanne B. Branowicki, Patricia Hanley, Diane TI Nursing leadership orientation - A competency and preceptor model to facilitate new leader success SO JOURNAL OF NURSING ADMINISTRATION LA English DT Article C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Childrens Hosp Boston, Med Patient Serv, Boston, MA 02115 USA. RP Conley, SB (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM Susanne_Conley@dfci.harvard.edu NR 14 TC 9 Z9 9 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-0443 J9 J NURS ADMIN JI J. Nurs. Adm. PD NOV PY 2007 VL 37 IS 11 BP 491 EP 498 DI 10.1097/01.NNA.0000295612.48065.ff PG 8 WC Nursing SC Nursing GA 232DL UT WOS:000250998300006 PM 17975465 ER PT J AU Larkin, ME Griffith, CA Capasso, VA Cierpial, C Gettings, R Walsh, K O'Malley, C AF Larkin, Mary E. Griffith, Catherine A. Capasso, Virginia A. Cierpial, Chelby Gettings, Rise Walsh, Kathleen O'Malley, Catherine TI Promoting research utilization using a conceptual framework SO JOURNAL OF NURSING ADMINISTRATION LA English DT Article ID IMPLEMENTATION C1 Massachusetts Gen Hosp, Ctr Diabet, Nursing Res Comm, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Heart, Cardiac Surg Div, Nursing Res Comm, Boston, MA 02114 USA. Harvard Univ, Sch Med, Yvonne L Munn Ctr Nursing Res, Nursing Res Comm, Boston, MA USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Boston, MA 02114 USA. Massachusetts Gen Hosp, Emergency Dept, Boston, MA 02114 USA. RP Larkin, ME (reprint author), Massachusetts Gen Hosp, Ctr Diabet, Nursing Res Comm, 50 Staniford St,Ste 340, Boston, MA 02114 USA. EM mlarkin1@partners.org NR 9 TC 7 Z9 9 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0002-0443 J9 J NURS ADMIN JI J. Nurs. Adm. PD NOV PY 2007 VL 37 IS 11 BP 510 EP 516 DI 10.1097/01.NNA.0000295617.26980.d1 PG 7 WC Nursing SC Nursing GA 232DL UT WOS:000250998300009 PM 17975468 ER PT J AU Olsen, J Papadaki, M Troulis, M Kaban, LB O'Neill, MJ Donoff, B AF Olsen, James Papadaki, Maria Troulis, Maria Kaban, Leonard B. O'Neill, Mary J. Donoff, Bruce TI Using ultrasound to visualize the lingual nerve SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID INFERIOR ALVEOLAR; REPAIR; REMOVAL; INJURY; DAMAGE; MANAGEMENT AB Purpose: The purpose of this study was to assess the effectiveness of ultrasonography in visualizing the lingual nerve, calculating its distance from the lingual cortex at the area of the third molar, and in detecting injuries. Materials and Methods: Using a standardized protocol, lingual nerve dissections were performed in Yorkshire pig cadaver heads. After nerve isolation was confirmed, the nerve was left intact, fully transected, or partially transected. The dissection flap was repositioned and the pig heads were given to 3 blinded evaluators. Using a handheld ultrasound device, the evaluators were asked to determine the status of the nerve and categorize their finding as intact, fully transected, or partially transected. The recorded ultrasound images from the 9 study specimens were then analyzed and the distances of the lingual nerves from the alveolus were measured. Results: After becoming familiar with the ultrasonographic appearance of the lingual nerve, all of the evaluators were able to visualize and identify the nerve using the ultrasound machine. Lingual nerve injuries were accurately categorized in 17 out of the 27 total attempts (success rate, 63%). The average distance of the nerve from the alveolar cortex was measured to be an average distance of 1 mm. Conclusion: The results of this study indicate that ultrasonography can be effectively used to visualize the lingual nerve. (C) 2007 American Association of Oral and Maxillofacial Surgeons. C1 Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, Boston, MA 02115 USA. Harvard Univ, Sch Dent Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Donoff, B (reprint author), Harvard Univ, Sch Dent Med, Dept Oral & Maxillofacial Surg, 188 Longwood Ave, Boston, MA 02115 USA. EM bruce_donoff@hsdm.harvard.edu NR 26 TC 9 Z9 9 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 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD NOV PY 2007 VL 65 IS 11 BP 2295 EP 2300 DI 10.1016/j.jams.2007.06.647 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 226XQ UT WOS:000250622200025 PM 17954328 ER PT J AU Goldwaser, BR Cbuang, SK Kaban, LB August, M AF Goldwaser, Batya R. Cbuang, Sung-Kiang Kaban, Leonard B. August, Mereditb TI Risk factor assessment for the development of osteoradionecrosis SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID PATIENTS RECEIVING RADIOTHERAPY; MANDIBULAR BONE COMPLICATIONS; HYPERBARIC-OXYGEN THERAPY; SQUAMOUS-CELL CARCINOMAS; RADIATION-THERAPY; ORAL CAVITY; DENTAL EXTRACTIONS; JAWS; OSTEONECROSIS; HEAD AB Purpose: Osteoradionecrosis (ORN) of the jaws has been extensively studied. However, controversy still exists regarding its etiology, risk factors, and the underlying mechanism of disease. The purpose of this study was to identify and evaluate significant risk factors for the development of ORN. Patients and Methods: This was a retrospective cohort study of 82 Massachusetts General Hospital patients radiated for head and neck cancer between 1984 and 2005. Patient records were reviewed to collect demographic, information, medical and dental history (including dental intervention or trauma), tumor specific data, treatment details, and follow-up. Biologic variables (ie, age and gender) of potential significance were also evaluated. The major outcome variable was the development of ORN or lack of development of ORN. The time from radiation to ORN, or for non-ORN patients, time to last follow-up. visit, was computed. Univariate analyses identified candidate variables associated with ORN (P < .15). Cox proportional hazards regression was used to evaluate these candidate variables as well as biologically relevant variables. Significant prognostic factors for the development of ORN (P < .05) were identified. Results: Multivariate regression identified the following variables as significantly associated with decreased ORN risk: higher body mass index (P = .02) and use of steroids (P = .02). Radiation dose greater than 66 Gray (P = .03) was associated with an increased ORN risk. Conclusions: Optimization of nutritional status, use of steroids, and limitation of total radiation dose may minimize the risk of ORN. (c) 2007 American Association of Oral and Maxillofacial Surgeons. C1 Harvard Univ, Dept Oral & Maxillofacial Surg, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP August, M (reprint author), Harvard Univ, Dept Oral & Maxillofacial Surg, Sch Med, Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02115 USA. EM Maugust@Partners.org NR 41 TC 29 Z9 31 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 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD NOV PY 2007 VL 65 IS 11 BP 2311 EP 2316 DI 10.1016/j.joms.2007.05.021 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 226XQ UT WOS:000250622200027 PM 17954330 ER PT J AU Hanson, GR Suggs, JF Kwon, YM Freiberg, AA Li, G AF Hanson, George R. Suggs, Jeremy F. Kwon, Young-Min Freiberg, Andrew A. Li, Guoan TI In vivo anterior tibial post contact after posterior stabilizing total knee arthroplasty SO JOURNAL OF ORTHOPAEDIC RESEARCH LA English DT Article DE primary posterior stabilizing total knee arthroplasty; tibial polyethylene post impingement; articular contact; in vivo; fluoroscopy ID KINEMATICS; IMPINGEMENT; FRACTURE; PROSTHESIS; SYSTEM; DAMAGE; JOINT AB Anterior polyethylene post failure in posterior stabilizing total knee arthroplasty (TKA) has been reported in recent patient follow-up studies. However, no data have been reported on the biomechanic interaction between the anterior tibial post and femoral component in posterior stabilizing TKA patients under physiological conditions. The objective of this study was to measure the in vivo anterior tibial post contact area at full knee extension using a dual-orthogonal fluoroscopic imaging technique. Eleven osteoarthritic patients were investigated after posterior stabilizing TKA to measure the contact between the femoral component box and anterior aspect of the tibial post. Anterior tibial post contact, ranging between 0.5 and 80.9 mm(2), was detected in 63% of the healthy patients (seven out of the eleven patients) at weight-bearing full extension of the knee. The patients with anterior tibial post contact had significantly higher hyperextension angles (-8.4 +/- 4.3 degrees) than those without contact (1.4 +/- 7.2 degrees). A statistically significant difference was also detected in the femoral component flexion with respect to the femoral shaft between the patients with anterior post contact (2.7 +/- 2.7 degrees) and without anterior post contact (-1.3 +/- 2.2 degrees). These data indicated that anterior post contact did occur in hyperextension within posterior stabilizing TKA patients. While excessive anterior tibial post contact may cause polyethylene wear and potentially lead to post failure, the tibial post may also act as a substitute for the ACL at low flexion, thus providing stability to the joint after posterior stabilizing TKA. (C) 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. C1 Massachusetts Gen Hosp, Harvard Univ, Sch Med, Bioengn Lab,Dept Orthopaed Surg, Boston, MA 02115 USA. RP Li, G (reprint author), Massachusetts Gen Hosp, Harvard Univ, Sch Med, Bioengn Lab,Dept Orthopaed Surg, Boston, MA 02115 USA. EM gli1@partners.org NR 19 TC 14 Z9 15 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0736-0266 J9 J ORTHOP RES JI J. Orthop. Res. PD NOV PY 2007 VL 25 IS 11 BP 1447 EP 1453 DI 10.1002/jor.20417 PG 7 WC Orthopedics SC Orthopedics GA 228NX UT WOS:000250737700006 PM 17557322 ER PT J AU Kudsk, KA Gomez, FE Kang, W Ueno, C AF Kudsk, Kenneth A. Gomez, F. Enrique Kang, Woodae Ueno, Chikara TI Enteral feeding of a chemically defined diet preserves pulmonary immunity but not intestinal immunity: The role of lymphotoxin beta receptor SO JOURNAL OF PARENTERAL AND ENTERAL NUTRITION LA English DT Article ID RESPIRATORY-TRACT IMMUNITY; LYMPHOID-TISSUE; MUCOSAL IMMUNITY; PARENTERAL-NUTRITION; EXPRESSION; BLOCKADE; ROUTE AB Background: Compared with chow or a complex enteral diet (CED), IV administration of a parenteral nutrition solution (IV-PN) impairs intestinal and respiratory mucosal immunity, resulting in cellular and immunoglobulin A (IgA) defects in the intestine and impaired respiratory antiviral and antibacterial defenses. PN given intragastrically (IG-PN) impairs intestinal immunity similar to IV-PN but preserves antiviral defences and partially preserves antibacterial defenses. Lymphotoxin 0 receptor (LT beta R) is a molecule essential for development and organization of lymphoid tissue. It controls many molecules important in mucosal immune integrity. This study examines effects of route (IV or enteral) and type (PN, CED, or chow) on murine intestine and lung LT beta R expression. Methods: Forty-three mice randomly received IV-PN (n = 12), IG-PN (n = 11), IV saline + chow (chow; n = 11), or a CED (n = 9). After 5 days of feeding, intestinal and lung samples were obtained and processed for levels of LT beta R by Western blot. Results: IV-PN significantly reduced intestinal and lung LT beta R compared with CED and chow; IG-PN reduced LT beta R levels only in the intestine but preserved lung levels. Conclusions: Route and type of nutrition differentially influence molecular events in the intestinal and respiratory mucosal immune systems. Enteral feeding with any diet (complex or chemically defined) maintains lung LT beta R expression, whereas intestinal LT beta R levels are maintained only with CEDs (chow and CED). We hypothesize that LT beta R is responsible for the observed preservation of respiratory tract immunity with administration of a noncomplex, chemically defined enteral diet, whereas intestinal immunity is compromised with this diet. C1 William S Middleton Mem Vet Adm Med Ctr, Vet Adm Surg Serv, Madison, WI USA. Univ Wisconsin, Dept Surg, Coll Med & Publ Hlth, Madison, WI USA. RP Kudsk, KA (reprint author), 600 Highland Ave,H4-736 CSC, Madison, WI 53792 USA. EM kudsk@surgery.wisc.edu FU NIGMS NIH HHS [R01 GM53439] NR 18 TC 6 Z9 6 U1 0 U2 1 PU AMER SOC PARENTERAL & ENTERAL NUTRITION PI SILVER SPRING PA 8630 FENTON STREET SUITE 412, SILVER SPRING, MD 20910 USA SN 0148-6071 J9 JPEN-PARENTER ENTER JI J. Parenter. Enter. Nutr. PD NOV-DEC PY 2007 VL 31 IS 6 BP 477 EP 481 DI 10.1177/0148607107031006477 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 227VU UT WOS:000250686700005 PM 17947602 ER PT J AU Bianchi, MT Botzolakis, EJ Haas, KF Fisher, JL Macdonald, RL AF Bianchi, Matt T. Botzolakis, Emmanuel J. Haas, Kevin F. Fisher, Janet L. Macdonald, Robert L. TI Microscopic kinetic determinants of macroscopic currents: insights from coupling and uncoupling of GABA(A) receptor desensitization and deactivation SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID STRUCTURAL DETERMINANTS; ACETYLCHOLINE-RECEPTOR; NICOTINIC RECEPTOR; M2 DOMAIN; CHANNEL; MUTATION; SUBUNIT; BINDING; ALPHA-1-BETA-2-GAMMA-2; MODULATION AB The time course of inhibitory postsynaptic currents (IPSCs) reflects GABA(A) receptor deactivation, the process of current relaxation following transient activation. Fast desensitization has been demonstrated to prolong deactivation, and these processes have been described as being 'coupled'. However, the relationship between desensitization and deactivation remains poorly understood. We investigated the 'uncoupling' of GABAA receptor macroscopic desensitization and deactivation using experimental conditions that affected these two processes differently. Changing agonist affinity preferentially altered deactivation, changing agonist concentration preferentially altered macroscopic desensitization, and a pore domain mutation prolonged deactivation despite blocking fast desensitization. To gain insight into the mechanistic basis for coupling and uncoupling, simulations were used to systematically evaluate the interplay between agonist affinity, gating efficacy, and desensitized state stability in shaping macroscopic desensitization and deactivation. We found that the influence of individual kinetic transitions on macroscopic currents depended not only on model connectivity, but also on the relationship among transitions within a given model. In addition, changing single rate constants differentially affected macroscopic desensitization and deactivation, thus providing parsimonious kinetic explanations for experimentally observed uncoupling. Finally, these findings permitted development of an algorithmic framework for kinetic interpretation of experimental manipulations that alter macroscopic current properties. C1 Massachusetts Gen Hosp, Brigham & Womens Hosp, Boston, MA 02114 USA. Vanderbilt Univ, Program Neurosci, Nashville, TN 37232 USA. Vanderbilt Univ, Dept Neurol, Nashville, TN 37232 USA. Vanderbilt Univ, Dept Physiol & Mol Biophys, Nashville, TN 37232 USA. Vanderbilt Univ, Dept Pharmacol, Nashville, TN 37232 USA. Univ S Carolina, Sch Med, Dept Pharmacol Physiol & Neurosci, Columbia, SC 29208 USA. RP Macdonald, RL (reprint author), Vanderbilt Univ, Med Ctr, Dept Neurol, 6140 Med Res Bldg 111,465 21st Ave, Nashville, TN 37232 USA. EM robert.macdonald@vanderbilt.edu RI Botzolakis, Emmanuel/B-9828-2008 FU NIGMS NIH HHS [T32 GM007347, T32 GM07347]; NINDS NIH HHS [R01 NS33300, R01 NS033300, NS045950, R01 NS045950] NR 46 TC 19 Z9 20 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD NOV 1 PY 2007 VL 584 IS 3 BP 769 EP 787 DI 10.1113/jphysiol.2007.142364 PG 19 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 234AD UT WOS:000251132100008 PM 17884921 ER PT J AU Vanneste, G Dhaese, I Sips, P Buys, E Brouckaert, P Lefebvre, RA AF Vanneste, Gwen Dhaese, Ingeborg Sips, Patrick Buys, Emmanuel Brouckaert, Peter Lefebvre, Romain A. TI Gastric motility in soluble guanylate cyclase alpha(1) knock-out mice SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID NITRIC-OXIDE SYNTHASE; VASOACTIVE INTESTINAL POLYPEPTIDE; SMOOTH-MUSCLE; DEFICIENT MICE; GASTROINTESTINAL-TRACT; BAY 41-2272; KINASE I; FUNDUS; RELAXATION; NO AB The principal target of the relaxant neurotransmitter nitric oxide (NO) is soluble guanylate cyclase (sGC). As the alpha(1)beta(1)-isoform of sGC is the predominant one in the gastrointestinal tract, the aim of this study was to investigate the role of sGC in nitrergic regulation of gastric motility in male and female sGC alpha(1) knock-out (KO) mice. In circular gastric fundus muscle strips, functional responses and cGMP levels were determined in response to nitrergic and non-nitrergic stimuli. sGC subunit mRNA expression in fundus was measured by real-time RT-PCR; in vivo gastric emptying of a phenol red meal was determined. No changes were observed in sGC subunit mRNA levels between wild-type (WT) and KO tissues. Nitrergic relaxations induced by short trains of electrical field stimulation (EFS) were abolished, while those by long trains of EFS were reduced in KO strips; the latter responses were abolished by 1H[1,2,4,] oxadiazolo [4,3-a]quinoxalin-I-one (ODQ). The relaxations evoked by exogenous NO and the NO-independent sGC activator BAY 41-2272 were reduced in KO strips but still sensitive to ODQ. Relaxations induced by vasoactive intestinal peptide (VIP) and 8-bromo-cGMP were not influenced. Basal cGMP levels were decreased in KO strips but NO, long train EFS and BAY 41-2272 still induced a moderate ODQ-sensitive increase in cGMP levels. Gastric emptying, measured at 15 and 60 min, was increased at 15 min in male KO mice. sGC alpha(1)beta(1) plays an important role in gastric nitrergic relaxation in vitro, but some degree of nitrergic relaxation can occur via sGC alpha(2)beta(1) activation in sGC alpha(1) KO mice, which contributes to the moderate in vivo consequence on gastric emptying. C1 Univ Ghent, Heymans Inst Pharmacol, B-9052 Ghent, Belgium. VIB, Dept Mol Biomed Res, Ghent, Belgium. Univ Ghent, Dept Biol Mol, Ghent, Belgium. Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. RP Lefebvre, RA (reprint author), Heymans Inst Pharmacol, De Pintelaan 185, B-9000 Ghent, Belgium. EM romain.lefebvre@ugent.be RI Tavares, Antonio/A-7115-2008; OI Sips, Patrick/0000-0001-9241-5980 NR 55 TC 20 Z9 21 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD NOV 1 PY 2007 VL 584 IS 3 BP 907 EP 920 DI 10.1113/jphysiol.2007.140608 PG 14 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 234AD UT WOS:000251132100017 PM 17717014 ER PT J AU Gordon, PL Sakkas, GK Doyle, JW Shubert, T Johansen, KL AF Gordon, Patricia L. Sakkas, Giorgos K. Doyle, Julie W. Shubert, Tiffany Johansen, Kirsten L. TI Relationship between vitamin D and muscle size and strength in patients on hemodialysis SO JOURNAL OF RENAL NUTRITION LA English DT Article ID CHRONIC-RENAL-FAILURE; SKELETAL-MUSCLE; 1,25-DIHYDROXYVITAMIN-D LEVELS; CARDIOVASCULAR MORTALITY; D METABOLITES; D-DEFICIENT; DISEASE; RATS; PERFORMANCE; 1,25-DIHYDROXYCHOLECALCIFEROL AB Objective: Vitamin D has various actions in skeletal muscle. The purpose of this study was to compare lower-limb muscle size and strength in hemodialysis (HD) patients being treated with 1,25-dihydroxyvitamin D (calcitriol) or a 1,25-dihydroxyvitamin D analogue (paricalcitol) with lower-limb muscle size and strength in HD patients who were receiving none. Design: This was a retrospective, cross-sectional study. Setting: This study was performed in outpatient HD centers. Patients: Hemodialysis patients receiving calcitriol or paricalcitol (active vitamin D) for control of secondary hyperparathyroidism (VitD, n = 49) were compared with HD patients who were not (n = 30). Main Outcome Measures: The main outcome measures included the cross-sectional areas (CSAs) of the thigh and tibialis anterior muscles by magnetic resonance imaging, and three measures of strength: the three-repetition maximum (3RM) for knee extension (isotonic), the peak torque of knee extensors (isokinetic), and maximal voluntary contraction of the ankle dorsiflexor muscles (isometric). Results: There were no differences in age, weight, dialysis vintage, or intact parathyroid hormone levels between groups, although serum albumin was higher in the VitD group (P < .05). Patients in the VitD group had a larger thigh-muscle CSA (P < .05) and were stronger across all strength measures (P < .05) after controlling for age and gender (by analysis of covariance). When all analyses were subsequently adjusted for serum albumin concentration, only the difference in 3RM knee-extension strength lost significance. There were no significant differences in any measurements between patients who received calcitriol or paricalcitol. Conclusion: Treatment with active vitamin D was associated with greater muscle size and strength in this cohort of HD patients. (C) 2007 by the National Kidney Foundation, Inc. C1 Univ Calif San Francisco, Sch Nursing, Dept Physiol Nursing, San Francisco, CA 94143 USA. No California Inst Res & Educ, San Francisco, CA USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Univ Thessaly, Sch Hlth Sci, Larisa, Greece. Univ N Carolina, Sch Med, Chapel Hill, NC USA. San Francisco Vet Adm Med Ctr, Nephrol Sect, San Francisco, CA USA. RP Gordon, PL (reprint author), Univ Calif San Francisco, Sch Nursing, Dept Physiol Nursing, 2 Koret Way, San Francisco, CA 94143 USA. EM patricia.gordon@nursing.ucsf.edu OI Sakkas, Giorgos/0000-0002-2462-995X FU NCRR NIH HHS [M01 RR000083, M01 RR000083-430502]; NIDDK NIH HHS [R01 DK056182, R01 DK056182-01, R01 DK056182-02, R01 DK056182-03, R01 DK056182-04, R01-DK56182] NR 42 TC 18 Z9 19 U1 2 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 1051-2276 J9 J RENAL NUTR JI J. Renal Nutr. PD NOV PY 2007 VL 17 IS 6 BP 397 EP 407 DI 10.1053/j.jrn.2007.06.001 PG 11 WC Nutrition & Dietetics; Urology & Nephrology SC Nutrition & Dietetics; Urology & Nephrology GA 234FQ UT WOS:000251146500005 PM 17971312 ER PT J AU Roberts, WN Liang, MH AF Roberts, W. Neal Liang, Matthew H. TI It takes a village to craft a clinical guideline SO JOURNAL OF RHEUMATOLOGY LA English DT Editorial Material ID ANKYLOSING-SPONDYLITIS; QUALITY C1 Brigham & Womens Hosp, Robert B Brigham Arthritis & Musculoskeletal Dis, Sect Clin Sci, Boston, MA 02115 USA. Virginia Commonwealth Univ, Med Coll Virginia Hosp, Richmond, VA USA. Boston VA Healthcare Syst, Rheumatol Sect, Boston, MA USA. RP Liang, MH (reprint author), Brigham & Womens Hosp, Robert B Brigham Arthritis & Musculoskeletal Dis, Sect Clin Sci, 75 Francis St, Boston, MA 02115 USA. EM mliang@partners.org NR 20 TC 0 Z9 0 U1 0 U2 0 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD NOV PY 2007 VL 34 IS 11 BP 2123 EP 2125 PG 3 WC Rheumatology SC Rheumatology GA 228WT UT WOS:000250764000001 PM 17985410 ER PT J AU Clavert, P Millett, PJ Warner, JJP AF Clavert, Philippe Millett, Peter J. Warner, Jon J. P. TI Glenoid resurfacing: What are the limits to asymmetric reaming for posterior erosion? SO JOURNAL OF SHOULDER AND ELBOW SURGERY LA English DT Article ID TOTAL SHOULDER ARTHROPLASTY; PRIMARY GLENOHUMERAL OSTEOARTHRITIS; BONE; VERSION; HEMIARTHROPLASTY; TOMOGRAPHY; COMPONENTS; JOINT AB Eccentric posterior glenoid erosion is a common condition in osteoarthritis. No limits have ever been placed on the degree of eccentric erosion that can be corrected while still maintaining sufficient bone stock to implant a glenoid securely. Five cadaveric scapulae were dissected. Posterior glenoid erosion was created to simulate retroversion of 15 degrees or more. A computed tomography (CT) scan confirmed the degree of glenoid retroversion. The glenoid was then reshaped to correct the glenoid retroversion to neutral, and a glenoid component with central and peripheral pegs was inserted. A second CT scan confirmed the correction to neutral and also evaluated the fit of the component into the glenoid. In all 5 experimental cases, at least I of the 4 pegs penetrated the glenoid vault. In I case, there was a fracture of the anterior rim. Glenoid retroversion of 15 degrees or more cannot be satisfactorily corrected simply by reaming to lower the anterior edge of the glenoid and restore neutral version when using a glenoid component with peripheral pegs. C1 [Clavert, Philippe; Millett, Peter J.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Harvard Shoulder Serv, Boston, MA 02114 USA. RP Warner, JJP (reprint author), Harvard Shoulder Serv, Yawkey Ambulatory Bldg,Ste 3G,5S Fruit St, Boston, MA 02114 USA. EM jwarner@partners.org NR 29 TC 43 Z9 43 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 1058-2746 J9 J SHOULDER ELB SURG JI J. Shoulder Elbow Surg. PD NOV-DEC PY 2007 VL 16 IS 6 BP 843 EP 848 DI 10.1016/j.jse.2007.03.015 PG 6 WC Orthopedics; Sport Sciences; Surgery SC Orthopedics; Sport Sciences; Surgery GA 243AR UT WOS:000251767800026 PM 18061118 ER PT J AU George, EO Armstrong, D Catalano, PJ Srivastava, DK AF George, E. Olusegun Armstrong, Dale Catalano, Paul J. Srivastava, Deo Kumar TI Regression models for analyzing clustered binary and continuous outcomes under an assumption of exchangeability SO JOURNAL OF STATISTICAL PLANNING AND INFERENCE LA English DT Article DE clustered exchangeable random variables; estimating equations; developmental toxicity studies ID LONGITUDINAL DATA-ANALYSIS; LATENT VARIABLE MODELS; DEVELOPMENTAL TOXICITY; CATEGORICAL-DATA; RISK-ASSESSMENT; DISCRETE AB Scientific experiments commonly result in clustered discrete and continuous data. Existing methods for analyzing such data include the use of quasi-likelihood procedures and generalized estimating equations to estimate marginal mean response parameters. In applications to areas such as developmental toxicity studies, where discrete and continuous measurements are recorded on each fetus, or clinical ophthalmologic trials, where different types of observations are made on each eye, the assumption that data within cluster are exchangeable is often very reasonable. We use this assumption to formulate fully parametric regression models for clusters of bivariate data with binary and continuous components. The regression models proposed have marginal interpretations and reproducible model structures. Tractable expressions for likelihood equations are derived and iterative schemes are given for computing efficient estimates (MLEs) of the marginal mean, correlations, variances and higher moments. We demonstrate the use the 'exchangeable' procedure with an application to a developmental toxicity study involving fetal weight and malformation data. (C) 2007 Elsevier B.V. All rights reserved. C1 Memphis State Univ, Dept Math Sci, Memphis, TN 38152 USA. Univ Mississippi, Dept Math, Oxford, MS 38677 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. St Jude Childrens Res Hosp, Dept Biostat, Memphis, TN 38105 USA. RP George, EO (reprint author), Memphis State Univ, Dept Math Sci, Memphis, TN 38152 USA. EM eogeorge@memphis.edu NR 28 TC 3 Z9 3 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-3758 J9 J STAT PLAN INFER JI J. Stat. Plan. Infer. PD NOV 1 PY 2007 VL 137 IS 11 BP 3462 EP 3474 DI 10.1016/j.jspi.2007.03.024 PG 13 WC Statistics & Probability SC Mathematics GA 205UM UT WOS:000249140100023 ER PT J AU Hornicek, FJ AF Hornicek, Francis J. TI RE: Local control in nonmetastatic pelvic Ewing's sarcoma patients: Outcome and analysis, by Donati, D, et al. SO JOURNAL OF SURGICAL ONCOLOGY LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Sarcoma & Connect Tissue Oncol, Boston, MA USA. RP Hornicek, FJ (reprint author), 55 Fruit Str, GRB 604B, Boston, MA USA. EM fhornicek@partners.org NR 5 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0022-4790 J9 J SURG ONCOL JI J. Surg. Oncol. PD NOV 1 PY 2007 VL 96 IS 6 BP 453 EP 454 DI 10.1002/jso.20753 PG 2 WC Oncology; Surgery SC Oncology; Surgery GA 231ZD UT WOS:000250986800003 PM 17654523 ER PT J AU Segara, D Krop, IE Garber, JE Winer, E Harris, L Bellon, JR Birdwell, R Lester, S Lipsitz, S Iglehart, JD Golshan, M AF Segara, Davendra Krop, Ian E. Garber, Judy E. Winer, Eric Harris, Lyndsay Bellon, Jennifer R. Birdwell, Robyn Lester, Susan Lipsitz, Stuart Iglehart, J. Dirk Golshan, Mehra TI Does MRI predict pathologioc tumor response in women with breast cancer undergoing preoperative chemotherapy? SO JOURNAL OF SURGICAL ONCOLOGY LA English DT Article DE breast MRI; neoadjuvant therapy; breast cancer ID NEOADJUVANT CHEMOTHERAPY; PHYSICAL-EXAMINATION; MAMMOGRAPHY; SIZE; ULTRASOUND; ACCURACY; SONOGRAPHY; EXPERIENCE; ULTRASONOGRAPHY; CONSERVATION AB Background: Neoadjuvant chemotherapy precludes the accurate pre-surgical pathologic measurement of tumor size. The purpose of this study is to review imaging studies performed in patients who received preoperative chemotherapy prior to surgery and determine whether MRI, ultrasound (US) or physical exam best predicted final pathologic tumor size. Methods: Stage I, II, and III breast cancer patients were treated with neoadjuvant therapy on trial. As part of the trials, women underwent MRI, US, and physical exam prior to the start of therapy and 1 week after completion of neoadjuvant chemotherapy. Results: Of the 68 patients with MRI data, the correlation coefficient (r) of MRI to pathologic size of tumor was r=0.749. Among the 52 patients who had an US assessment the correlation of US to pathology was r = 0.612. Sixty-two patients had physical exam data, and the correlation of examination to pathology size was r = 0.439. MRI correctly predicted 8 of 11 complete responders and accurately evaluated the size of non-responders to neoadjuvant therapy (r = 0.869) Conclusions: In a select group of women undergoing neoadjuvant therapy for invasive breast cancer, MRI best predicted pathology response. The use of MRI in neoadjuvant therapy may allow for accurate prediction of patients eligible for breast conservation. C1 Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Golshan, M (reprint author), Brigham & Womens Hosp, Dept Surg, 75 Francis St, Boston, MA 02115 USA. EM mgolshan@partners.org NR 32 TC 59 Z9 63 U1 1 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0022-4790 J9 J SURG ONCOL JI J. Surg. Oncol. PD NOV 1 PY 2007 VL 96 IS 6 BP 474 EP 480 DI 10.1002/jso.20856 PG 7 WC Oncology; Surgery SC Oncology; Surgery GA 231ZD UT WOS:000250986800008 PM 17640031 ER PT J AU Shera, CA AF Shera, Christopher A. TI Laser amplification with a twist: Traveling-wave propagation and gain functions from throughout the cochlea SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID AUDITORY-NERVE FIBERS; GUINEA-PIG COCHLEA; OUTER HAIR-CELLS; BASILAR-MEMBRANE; OTOACOUSTIC EMISSIONS; COHERENT REFLECTION; 3-DIMENSIONAL MODEL; NONLINEAR MECHANICS; MOSSBAUER TECHNIQUE; CHINCHILLA-COCHLEA AB Except at the handful of sites explored by the inverse method, the,characteristics-indeed, the very existence-of traveling-wave amplification in the mammalian cochlea remain largely unknown. Uncertainties are especially pronounced in the apex, where mechanical and electrical measurements lack the independent controls necessary for assessing damage to the preparation. At a functional level, the form and amplification of cochlear traveling waves are described by quantities known as propagation and gain functions. A method for deriving propagation and gain functions from basilar-membrane mechanical transfer functions is presented and validated by response reconstruction. Empirical propagation and gain functions from locations throughout the cochlea are obtained in mechanically undamaged preparations by applying the method to published estimates of near-threshold basilar membrane responses derived from Wiener-kernel (chinchilla) and zwuis analysis (cat) of auditory-nerve responses to broadband stimuli. The properties of these functions, and their variation along the length of the cochlea, are described. In both species, and at all locations examined, the gain functions reveal a region of positive power gain basal to the wave peak. The results establish the-existence of traveling-wave amplification throughout the cochlea, including the apex. The derived propagation and gain functions resemble those characteristic of an active optical medium but rotated by 90 degrees in-the complex plane. Rotation of the propagation and gain functions enables the mammalian cochlea to operate as a wideband, hydromechanical laser analyzer. (c) 2007 Acoustical Society of America. C1 Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. RP Shera, CA (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab Auditory Physiol, 243 Charles St, Boston, MA 02114 USA. FU NIDCD NIH HHS [R01 DC003687, R01 DC03687] NR 88 TC 40 Z9 40 U1 0 U2 3 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD NOV PY 2007 VL 122 IS 5 BP 2738 EP 2758 DI 10.1121/1.2783205 PN 1 PG 21 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 224MT UT WOS:000250451800028 PM 18189566 ER PT J AU Gallun, FJ Mason, CR Kidd, G AF Gallun, Frederick J. Mason, Christine R. Kidd, Gerald, Jr. TI The ability to listen with independent ears SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article; Proceedings Paper CT 29th Midwinter Meeting of the Association-for-Research-in-Otolaryngology CY FEB 05-08, 2006 CL Baltimore, MD SP Assoc Res Otolaryngol ID MASKING-LEVEL DIFFERENCES; INFORMATIONAL MASKING; SPEECH IDENTIFICATION; CANCELLATION THEORY; MONAURAL DETECTION; CONTRALATERAL CUE; WITHIN-EAR; INTERFERENCE; TASK; EQUALIZATION AB In three experiments, listeners identified speech processed into narrow bands and presented to the right ("target") ear. The ability of listeners to ignore (or even use) conflicting contralateral stimulation was examined by presenting various maskers to the target ear ("ipsilateral") and nontarget ear ("contralateral"). Theoretically, an absence of contralateral interference would imply selectively attending to only the target ear; the presence of interference from the contralateral stimulus would imply that listeners were unable to treat the stimuli at the two ears independently; and improved performance in the presence of informative contralateral stimulation would imply that listeners can process the signals at both ears and keep them separate rather than combining them. Experiments showed evidence of the ability to selectively process (or respond to) only the target ear in some, but not all, conditions. No evidence was found for improved performance due to contralateral stimulation. The pattern of interference found across experiments supports an interaction of stimulus-based factors (auditory grouping) and task-based factors (demand for processing resources) and suggests that listeners may not always be able to listen to the "better" ear even when it would be beneficial to do so. (c) 2007 Acoustical Society of America. C1 Boston Univ, Dept Speech Language & Hearing Sci, Boston, MA 02215 USA. Boston Univ, Hearing Res Ctr, Boston, MA 02215 USA. RP Gallun, FJ (reprint author), Natl Ctr Rehabil Auditory Res, Portland VA Med Ctr, 3710 SW US Vet Hosp Rd NCRAR, Portland, OR 97239 USA. EM Frederick.Gallun@va.gov RI Gallun, Frederick/G-3792-2012 OI Gallun, Frederick/0000-0002-4145-2199 FU NIDCD NIH HHS [DC00100, DC04545, DC04663, F32 DC006526, R01 DC004545] NR 39 TC 8 Z9 8 U1 0 U2 2 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD NOV PY 2007 VL 122 IS 5 BP 2814 EP 2825 DI 10.1121/1.2780143 PN 1 PG 12 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 224MT UT WOS:000250451800033 PM 18189571 ER PT J AU Levy, C Palat, SIT Kramer, AM AF Levy, Cari Palat, Sing-I T. Kramer, Andrew M. TI Physician practice patterns in nursing homes SO JOURNAL OF THE AMERICAN MEDICAL DIRECTORS ASSOCIATION LA English DT Review DE physician practices; practice models; nursing home; physician role ID HEALTH-CARE UTILIZATION; FEE-FOR-SERVICE; MANAGED CARE; NATIONAL-SURVEY; UNITED-STATES; RESIDENTS; PRACTITIONERS; HOSPITALIZATION; EDUCATION; EVERCARE AB This review of the literature describes models of physician practice in nursing homes including the barriers to increasing physician workforce in nursing homes and the impact of various physician practice models on quality of care in nursing homes. Traditional nursing home practice is first described followed by a review of the literature pertaining to nurse practitioners and physician assistants in nursing home practices, closed staffing models, managed care, and nursing home specialist models. Literature describing barriers to increasing the physician workforce in nursing homes is then presented including training, reimbursement, and malpractice insurance for physicians who work in nursing homes. Finally, the impact of physician practice models on quality of care is reviewed with a focus on frequency of visits, hospitalizations, cost-effectiveness, communication, and patient satisfaction. C1 Univ Colorado, Hlth Sci Ctr, Aurora, CO 80045 USA. Univ Colorado, Denver VA Med Ctr, Denver, CO 80220 USA. Univ Colorado, Hlth Sci Ctr, Div Hlthcare Policy & Res, Denver, CO USA. Denver Vet Affairs Med Ctr, Aurora, CO USA. Univ Colorado, Denver Hlth Sci Ctr, Div Geriatr Med, Denver, CO USA. RP Levy, C (reprint author), Univ Colorado, Hlth Sci Ctr, 13611 E Colfax Ave, Suite 100, Aurora, CO 80045 USA. EM Cari.Levy@uchsc.edu NR 76 TC 14 Z9 14 U1 1 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1525-8610 J9 J AM MED DIR ASSOC JI J. Am. Med. Dir. Assoc. PD NOV PY 2007 VL 8 IS 9 BP 558 EP 567 DI 10.1016/j.jamda.2007.06.015 PG 10 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 236YC UT WOS:000251338400003 PM 17998111 ER PT J AU Wagner, B Ricono, JM Gorin, Y Block, K Arar, M Riley, D Choudhury, GG Abboud, HE AF Wagner, Brent Ricono, Jill M. Gorin, Yves Block, Karen Arar, Mazen Riley, Dan Choudhury, Goutarn Ghosh Abboud, Hanna E. TI Mitogenic signaling via platelet-derived growth factor beta in metanephric mesenchymal cells SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID SMOOTH-MUSCLE-CELLS; AKT/PROTEIN KINASE-B; MESANGIAL CELLS; NAD(P)H OXIDASE; FACTOR-RECEPTOR; PHOSPHATIDYLINOSITOL 3'-KINASE; PDGF-RECEPTOR; DNA-SYNTHESIS; ACTIVATION; EXPRESSION AB Mice deficient in either platelet-derived growth factor (PDGF) B chain or PDGF receptor (PDGFR) beta lack mesangial cells. PDGF stimulates proliferation and migration of metanephric mesenchymal cells, from which mesangial cells are derived. Binding of PDGF to PDGFR-p induces autophosphorylation at specific tyrosine residues and activates various effector proteins, including phosphatidylinositol-3-kinase (PI3-K). This study explored the role of PI 3-K and reactive oxygen species (ROS) in PDGF-mediated signaling using cells established from wild-type and PDGFR-beta -/- metanephric blastemas at 11.5 days post-conception. PDGF-induced effects that were dependent on PI3-K activation were determined using PDGFR-beta -/- cells made to express "add-back" mutant PDGFR-beta capable of binding PI3-K. We found that PDGF is mitogenic for mesenchymal cells expressing PDGFR-beta, and PI3-K is an important regulator of PDGF-induced DNA synthesis. Activation of ERK1/2 is partially dependent on PI3-K, and both the PI3-K and MEK-ERK1/2 pathways contribute to PI3-K-dependent mitogenesis. In addition, PDGF-induced DNA synthesis in wild-type cells was found to be dependent on ROS that are generated downstream of PI3-K activation. Using antisense oligonucleotides and small interfering RNA, we determined that the NAD(P)H oxidase Nox4 produces these ROS that activate Akt and the MEK-ERK1/2 mitogenic cascade. In conclusion, the present study demonstrates Nox4 involvement in PDGF-induced DNA synthesis in metanephric mesenchymal cells and provides the first evidence that PDGF-induced PI3-K activity enhances production of ROS by Nox4. C1 Univ Texas, Hlth Sci Ctr, Dept Med, Div Nephrol, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Pediat, San Antonio, TX 78229 USA. S Texas Vet Hlth Care Syst, Inst Biotechnol, Dept Mol Med, San Antonio, TX USA. S Texas Vet Hlth Care Syst, Ctr Geriatr Res Educ & Clin, San Antonio, TX USA. RP Wagner, B (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Div Nephrol, 7703 Floyd Curl Dr,MC 7882, San Antonio, TX 78229 USA. EM wagnerb@uthscsa.edu OI Gorin, Yves/0000-0003-4048-6925; Wagner, Brent/0000-0002-7063-0142 FU NIDDK NIH HHS [DK-33665, R01 DK50190] NR 39 TC 18 Z9 19 U1 0 U2 2 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2007 VL 18 IS 11 BP 2903 EP 2911 DI 10.1681/ASN.2006111229 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 228NW UT WOS:000250737600018 PM 17942966 ER PT J AU Izawa, A Ueno, T Jurewicz, M Ito, T Tanaka, K Takahashi, M Ikeda, U Sobolev, O Fiorina, P Smith, RN Hynes, RO Abdi, R AF Izawa, Atsushi Ueno, Takuya Jurewicz, Mollie Ito, Toshiro Tanaka, Katsunori Takahashi, Masafumi Ikeda, Uichi Sobolev, Olga Fiorina, Paolo Smith, Rex Neal Hynes, Richard O. Abdi, Reza TI Importance of donor- and recipient-derived Selectins in cardiac allograft rejection SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID DEFICIENT MICE; P-SELECTIN; LEUKOCYTE RECRUITMENT; ADHESION MOLECULE-1; ENDOTHELIAL-CELLS; T-CELLS; INFLAMMATION; LIGANDS; SITES; LYMPHOCYTES AB The selectins expressed on activated endothelial cells (E- and P-selectin), leukocytes (L-selectin), and platelets (P-selectin) play crucial roles in the rolling and tethering of leukocytes. We explored the importance of donor and recipient selectins in acute and chronic cardiac allograft rejection using mice deficient in all three selectins (ELP-/-). In BALB/c recipients, survival of fully allomismatched hearts from ELP-/- C57BL/6 donors was almost double that of wild-type grafts. In ELP-/- cardiac allografts, mononuclear cell infiltration and vasculitis of intramyocardial coronary arteries were significantly reduced. Interestingly, ELP-/- grafts were rejected similarly in both the presence and the absence of recipient selectins, and both wild-type and ELP-/- recipients promptly rejected wild-type hearts. Alternative adhesive molecules such as alpha 4 beta 7 integrin may compensate for the lack of selectins and may mediate rejection in ELP-/- recipients. Chronic rejection was evaluated in a major histocompatibility complex (MHC) class II mismatch model using C57BL/6.C-H2(bm12) mice. While lack of selectins in recipients did not offer protection against chronic rejection, luminal stenosis of coronary arteries in ELP-/- grafts was markedly diminished. In conclusion, donor-derived selectins contribute to the development of both acute and chronic cardiac allograft rejection, and targeting donor selectins may open novel therapeutic approaches in clinical transplantation. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Transplantat Res Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Childrens Hosp, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg,Transplantat Unit, Boston, MA USA. MIT, Ctr Canc Res, Howard Hughes Med Inst, Cambridge, MA 02139 USA. Shinshu Univ, Grad Sch Med, Dept Organ Regenerat, Div Cardiovasc Sci, Matsumoto, Nagano 390, Japan. RP Abdi, R (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Transplantat Res Ctr, 221 Longwood Ave,3rd Fl, Boston, MA 02115 USA. EM rabdi@rics.bwh.harvard.edu FU NIAID NIH HHS [P01 AI50157] NR 32 TC 7 Z9 7 U1 0 U2 0 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2007 VL 18 IS 11 BP 2929 EP 2936 DI 10.1681/ASN.2006111261 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 228NW UT WOS:000250737600021 PM 17928506 ER PT J AU Johansen, KL Chertow, GM Jin, C Kutner, NG AF Johansen, Kirsten L. Chertow, Glenn M. Jin, Chengshi Kutner, Nancy G. TI Significance of frailty among dialysis patients SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID KIDNEY-DISEASE; WOMENS HEALTH; OLDER; DISABILITY AB The construct of frailty has been associated with adverse outcomes among elderly individuals, but the prevalence and significance of frailty among patients with end-stage renal disease have not been established. The aim of the current study was to determine the prevalence and predictors of frailty among a cohort of incident dialysis patients and to determine the degree to which frailty was associated with death and hospitalization. We studied a cohort of 2275 adults who participated in the Dialysis Morbidity and Mortality Wave 2 study, of whom two-thirds met our definition of frailty: a composite construct that incorporated poor self-reported physical functioning, exhaustion/fatigue, low physical activity, and undernutrition. Multivariable logistic regression analysis suggested that older age, female sex, and hemodialysis (rather than peritoneal dialysis) were independently associated with frailty. Cox proportional hazards modeling indicated that frailty was independently associated with higher risk of death (adjusted hazard ratio [HR] 2.24, 95% confidence interval [CI] 1.60-3.15) and with the combined outcome of death or hospitalization (adjusted HR 1.63, 95% CI 1.41-1.87). Frailty is extremely common and is associated with adverse outcomes among incident dialysis patients. Given its prevalence and consequences, increased research efforts should focus on interventions aimed to prevent or attenuate frailty in the dialysis population. C1 Univ Calif San Francisco, San Francisco VA Med Ctr, Nephrol Sect, San Francisco, CA 94121 USA. Univ Calif San Francisco, Div Nephrol, San Francisco, CA USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Emory Univ, Dept Rehabil Med, Atlanta, GA 30322 USA. RP Johansen, KL (reprint author), Univ Calif San Francisco, San Francisco VA Med Ctr, Nephrol Sect, 111J,4150 Clement St, San Francisco, CA 94121 USA. EM kirsten.johansen@ucsf.edu FU NIDDK NIH HHS [N01-DK-1-2450, N01-DK-1-2471] NR 19 TC 169 Z9 172 U1 0 U2 4 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2007 VL 18 IS 11 BP 2960 EP 2967 DI 10.1681/ASN.2007020221 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 228NW UT WOS:000250737600025 PM 17942958 ER PT J AU Choi, AI Rodriguez, RA Bacchetti, P Bertenthal, D Volberding, PA O'Hare, AM AF Choi, Andy I. Rodriguez, Rudolph A. Bacchetti, Peter Bertenthal, Daniel Volberding, Paul A. O'Hare, Ann M. TI Racial differences in end-stage renal disease rates in HIV infection versus diabetes SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; CHRONIC KIDNEY-DISEASE; SOCIOECONOMIC-STATUS; UNITED-STATES; ADMINISTRATIVE DATA; VETERAN POPULATION; SERUM CREATININE; NEPHROPATHY; DISPARITIES AB Few studies have compared the incidence of end-stage renal disease (ESRD) among individuals with the human immunodeficiency virus (HIV) and diabetes. We followed a national sample of 2,015,891 US veterans over a median peroid of 3.7 years for progression to ESRD. The age- and sex-adjusted incidence of ESRD (per 1000 person-years) among HIV-infected black patients was nearly an order of magnitude higher than among HIV-positive white patients, almost twice that of diabetic whites, and similar to that among diabetic blacks. In multivariate Cox proportional hazards analysis, diabetes was associated with an increased risk of ESRD among white patients, but HIV was not. Among black individuals, however, both HIV and diabetes conferred a similar increase in the risk of ESRD (4- to 5-fold increase compared to white individuals without HIV or diabetes). HIV and diabetes carry a similar risk of ESRD among black patients, highlighting the importance of developing strategies to prevent and treat renal disease among HIV-infected black individuals. C1 Univ Calif San Francisco, Renal Ctr, Dept Med, San Francisco Gen Hosp, San Francisco, CA 94110 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94110 USA. San Francisco VA Med Ctr, VA Res Enhancement Award Program, San Francisco, CA USA. Univ Washington, Seattle, WA 98195 USA. VA Puget Healthcare Syst, Dept Med, Seattle, WA USA. RP Choi, AI (reprint author), Univ Calif San Francisco, Renal Ctr, Dept Med, San Francisco Gen Hosp, Box 1341,Bldg 100,Room 350,1001 Potrero Ave, San Francisco, CA 94110 USA. EM andy.choi@ucsf.edu FU NIA NIH HHS [K23-AG028980-01]; NIAID NIH HHS [P30-AI27763]; NIDDK NIH HHS [T32-DK07219] NR 43 TC 75 Z9 76 U1 2 U2 4 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD NOV PY 2007 VL 18 IS 11 BP 2968 EP 2974 DI 10.1681/ASN.2007040402 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 228NW UT WOS:000250737600026 PM 17942954 ER PT J AU Weisbord, SD Fried, LF Mor, MK Resnick, AL Kimmel, PL Palevsky, PM Fine, MJ AF Weisbord, Steven D. Fried, Linda F. Mor, Maria K. Resnick, Abby L. Kimmel, Paul L. Palevsky, Paul M. Fine, Michael J. TI Associations of race and ethnicity with anemia management among patients initiating renal replacement therapy SO JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION LA English DT Article DE health disparities; end-stage renal disease; kidney; race/ethnicity ID CHRONIC KIDNEY-DISEASE; RECOMBINANT-HUMAN-ERYTHROPOIETIN; RACIAL-DIFFERENCES; UNITED-STATES; HEMODIALYSIS; DIALYSIS; HEMOGLOBIN; TRENDS; CARE; POPULATION AB Background : Many patients initiate renal replacement therapy with suboptimal anemia management. The factors contributing to this remain largely unknown. The aim of this study was to assess the associations of race and ethnicity with anemia care prior to the initiation of renal replacement therapy. Methods: Using data from the medical evidence form filed for patients who initiated renal replacement therapy between 1995-2003, we assessed racial and ethnic differences in pre-end-stage renal disease hematocrit levels, the use of erythropoiesis stimulation agents (ESAs), the proportion of patients with hernatocrit levels >= 33% and the proportion of patients with hernatocrit levels < 33% that did not receive ESA. We also examined secular trends in racial and ethnic differences in these parameters. Results: In multivariable analyses, non-Hispanic blacks had lower hematocrit levels (A hematocrit = -0.97%, 95% Cl: -1.00-0.94%), and were less likely to receive ESA (OR=0.82, 95% Cl: 0.81-0.84), to initiate renal replacement therapy with hematocit >= 33% (OR=0.78, 95% Cl: 0.77-0.79) or to receive ESA if the hematocrit was < 33% (OR=0.79, 95% Cl: 0.77-0.80) than non-Hispanic whites. White Hispanics also had lower hematocrit levels (A hematocrit = -0.42%, 95% Cl:-0.47% to -0.37%), and were less likely to receive ESA (OR=0.86, 95% Cl: 0.85-0.88), to have hematocrit levels >= 33% (OR=0.91, 95% Cl: 0.89-0.93) or to receive ESA if the hematocrit was < 33% (OR=0.85, 95% Cl: 0.83-0.87) than non-Hispanic whites. These disparities persisted over the eight-year study period. Conclusions: African-American race and Hispanic ethnicity are associated with suboptimal pre-end-stage renal disease anemia management. Efforts to improve anemia care should incorporate targeted interventions to decrease these disparities. C1 VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. VA Pittsburgh Healthcare Syst, Med Specialty Serv Line, Renal Sect, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Med, Renal Electrolyte Div, Pittsburgh, PA USA. Univ Pittsburgh, Sch Med, Dept Med, Div Gen Internal Med, Pittsburgh, PA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA. George Washington Univ, Med Ctr, Dept Med, Div Renal Dis & Hypertens, Washington, DC 20037 USA. RP Weisbord, SD (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Mailstop 111F-U,7E Room 120, Pittsburgh, PA USA. EM weisbordsd@upmc.edu FU NIAID NIH HHS [K24 AI001769] NR 29 TC 9 Z9 9 U1 1 U2 1 PU NATL MED ASSOC PI WASHINGON PA 1012 10TH ST, N W, WASHINGON, DC 20001 USA SN 0027-9684 J9 J NATL MED ASSOC JI J. Natl. Med. Assoc. PD NOV PY 2007 VL 99 IS 11 BP 1218 EP 1226 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 231GW UT WOS:000250935600001 PM 18020096 ER PT J AU Oxnard, GR Fidias, P Muzikansky, A Sequist, LV AF Oxnard, Geoffrey R. Fidias, Panos Muzikansky, Alona Sequist, Lecia V. TI Non-small cell lung cancer in octogenarians: Treatment practices and preferences SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE non-small cell lung cancer; octogenarian; elderly; patient preferences ID ELDERLY-PATIENTS; PHASE-II; AGE; RESECTION; SURVIVAL; OLDER; CHEMOTHERAPY; VINORELBINE; POPULATION; CISPLATIN AB Introduction: Among patients with non-small cell lung cancer (NSCLC), patients aged 80 or older have inferior survival. Treatment practices in this patient population are poorly described. In this report, we describe the treatment of a population of very elderly patients with NSCLC at a large teaching hospital. Methods: A retrospective chart review was performed of 111 outpatients with NSCLC aged 80 or older. Patient treatment regimens were evaluated for consistency with contemporaneous stage-specific guideline-recommended therapy (GRT). Attention was paid to how patient characteristics and attitudes influence therapy decisions. Results: Patients characteristics included median age of 82.6 years (range, 80-92), 30% stage I-II, 39% stage IV, 59% performance status 0-1, 25% performance status >= 2 (performance status unavailable for 15%). Eighty-four percent of the patients received some form of antineoplastic therapy, and 11% were treated with best supportive care alone. Of 34 patients with localized disease, 53% underwent tumor resection and 38% received definitive radiation. Of 70 patients with stage III or IV disease, 36% received cytotoxic chemotherapy and 27% received oral targeted therapy alone. Thirty-two percent of patients received the stage-specific GRT. Of the patients who did not receive GRT, 26% electively refused the offered GRT and 74% were not offered GRT. Conclusions: The vast majority of octogenarian patients with NSCLC receive antineoplastic therapy, but only one third of this population receives stage-specific GRT. Although many patients choose aggressive therapies, a small but clinically significant portion chose not to receive the offered GRT. More data are needed on appropriate therapy recommendations for this patient population. C1 Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Hosp Canc Ctr, Ctr Thorac Canc, Boston, MA 02114 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Biostat, Boston, MA USA. RP Sequist, LV (reprint author), Massachusetts Gen Hosp, Ctr Canc, 32 Fruit St,7th Flr, Boston, MA 02114 USA. EM LVSequist@partners.org NR 29 TC 22 Z9 22 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD NOV PY 2007 VL 2 IS 11 BP 1029 EP 1035 DI 10.1097/JTO.0b013e318158d4a2 PG 7 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 231HW UT WOS:000250938500008 PM 17975495 ER PT J AU Pandya, KJ Dahlberg, S Hidalgo, M Cohen, RB Lee, MTW Schiller, JH Johnson, DH AF Pandya, Kishan J. Dahlberg, Suzanne Hidalgo, Manuel Cohen, Roger B. Lee, Martin W. Schiller, Joan H. Johnson, David H. TI A randomized, phase II trial of two dose levels of temsirolimus (CCI-779) in patients with extensive-stage small-cell lung cancer who have responding or stable disease after induction chemotherapy: A trial of the eastern cooperative oncology group (E1500) SO JOURNAL OF THORACIC ONCOLOGY LA English DT Article DE small-cell lung cancer; temsirolimus; CCI-779; phase II study ID RAPAMYCIN; MTOR; INHIBITION AB Hypothesis: To study the progression-free survival (PFS) and toxicity with 25- or 250-mg doses of temsirolimus (CCI-779) after induction chemotherapy in patients with extensive small-cell lung cancer. Methods: Patients with either stable or responding disease to four to six cycles of cisplatin or carboplatin plus etoposide or irinotecan were randomized between 4 and 8 weeks after completion of induction therapy to receive either 25 or 250 mg of temsirolimus intravenously every week until disease progression. Results: Eighty-seven patients entered between January 2002 and December 2003, of whom 85 were eligible: 44 received 25 mg (arm A), and 41 received 250 mg (arm 13). The overall median follow-up time for all eligible patients was 34.6 months. Median age was 59 years (range, 39-80); 42 (49.4%) were male and 43 (50.6%) female; 12.9% had brain metastases. The overall median and 1-year PFS were 2.2 months (95% confidence interval [CI]: 1.8, 2.9) and 4.7% (95% Cl: 0.2%, 9.2%), respectively. The median PFS (95% CI) for ann A was 1.9 months (1.6, 2.3); for arm B, it was 2.5 months (1.9, 3.4; p = 0.24). The median overall survival from randomization was 8 months (95% Cl: 6.5, 9.5). Among the 86 patients with reported toxicities. 36 (42%) had grade 3 toxicities, the most common of which were thrombocytopenia, hypophosphatemia, and fatigue, and an additional 12 (14%) had grade 4 toxicities, the most common of which was neutropenia. No patients experienced lethal toxicities. Conclusion: Temsirolimus (CCI 779), given at 25 or 250 mg weekly, seemed not to increase the PFS in this patient population. C1 Univ Rochester, Rochester, NY USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Johns Hopkins Univ, Baltimore, MD USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Pk Nicollet Hlth Serv, St Louis, MO USA. Univ Texas, Dallas, TX 75230 USA. Vanderbilt Univ, Nashville, TN USA. RP Pandya, KJ (reprint author), Univ Rochester, James P Wilmot Canc Ctr, 601 Elmwood Ave, Rochester, NY 14642 USA. EM kishan_pandya@urmc.rochester.edu RI Johnson, David/A-7437-2009; HIDALGO, MANUEL/I-4995-2015 OI HIDALGO, MANUEL/0000-0002-3765-3318 FU NCI NIH HHS [CA11083, CA16116, CA21076, CA21115, CA23318, CA27525, CA49957, CA66636] NR 13 TC 91 Z9 95 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1556-0864 J9 J THORAC ONCOL JI J. Thorac. Oncol. PD NOV PY 2007 VL 2 IS 11 BP 1036 EP 1041 DI 10.1097/JTO.0b013e318155a439 PG 6 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 231HW UT WOS:000250938500009 PM 17975496 ER PT J AU Bauer, KA AF Bauer, K. A. TI Targeted inhibition of coagulation: oral agents show promise in phase III trials SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Editorial Material ID DIRECT THROMBIN INHIBITOR; NONVALVULAR ATRIAL-FIBRILLATION; MAJOR ORTHOPEDIC-SURGERY; VENOUS THROMBOEMBOLISM; STROKE PREVENTION; RANDOMIZED-TRIAL; KNEE REPLACEMENT; XIMELAGATRAN; WARFARIN; FONDAPARINUX C1 Harvard Univ, Sch Med, VA Boston Healthcare Syst, Boston, MA 02130 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02130 USA. RP Bauer, KA (reprint author), Harvard Univ, Sch Med, VA Boston Healthcare Syst, 150 S Huntington Ave, Boston, MA 02130 USA. EM kbauer@bidmc.harvard.edu NR 13 TC 5 Z9 5 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1538-7933 J9 J THROMB HAEMOST JI J. Thromb. Haemost. PD NOV PY 2007 VL 5 IS 11 BP 2175 EP 2177 DI 10.1111/j.1538-7836.2007.02742.x PG 3 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 228GQ UT WOS:000250718300002 PM 17764539 ER PT J AU Benacerraf, BR Shipp, TD Bromley, B Levine, D AF Benacerraf, Beryl R. Shipp, Thomas D. Bromley, Bryann Levine, Deborah TI What does magnetic resonance Imaging add to the prenatal sonographic diagnosis of ventriculomegaly? SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Article DE comparison; fetal central nervous system; prenatal magnetic resonance imaging; prenatal sonography; ventriculornegaly ID FETAL-BRAIN; DEDICATED NEUROSONOGRAPHY; CORPUS-CALLOSUM; ABNORMALITIES AB Objective. The purpose of this study was to determine the contribution of magnetic resonance imaging (MRI) in evaluating fetuses with the sonographic diagnosis of ventriculomegaly (VM). Methods. Over 4 years, consecutive fetuses with the sonographic diagnosis of VM at 1 facility who underwent prenatal MRI at a second facility were included. The roles of MRI and follow-up sonography were tabulated. The patients were analyzed in 2 groups based on the presence or absence of other central nervous system (CNS) abnormalities. Results. Twenty-six fetuses with a gestational age range of 17 to 37 weeks had sonographically detected VM (atria >= 10-29 mm), including 19 with mild VM (atria 10-12 mm). In group 1, 14 had isolated VM, 6 of which reverted to normal by the third trimester. Magnetic resonance imaging showed cerebellar hypoplasia not shown by sonography in 1 fetus and an additional finding of a mega cisterna magna in a second fetus. In group 2, 12 fetuses had VM and other CNS anomalies on sonography. Additional findings were seen with MRI in 10 of these fetuses, including migrational abnormalities (n = 4), porencephaly (n = 4), and 1 diagnosis each of abnormal myelination, hypoplasia of the corpus callosum, microcephaly, a kinked brain stem, cerebellar hypoplasia, and congenital infarction. There were significantly more fetuses with additional CNS anomalies found by MRI among those in group 2 compared with those in group I (Fisher exact test, P =.001). Conclusions. Although sonography is an accurate diagnostic modality for the evaluation of fetuses with VM, MRI adds important additional information, particularly in fetuses in whom additional findings other than an enlarged ventricle are seen sonographically. C1 Brigham & Womens Hosp, Dept Obstet & Gynecol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. RP Benacerraf, BR (reprint author), Diagnost Ultrasound Associates, 333 Longwood Ave, Boston, MA 02115 USA. FU NINDS NIH HHS [R29 NS037945-05, R29 NS037945-02, R29 NS037945-03, R29 NS037945-04]; PHS HHS [01998] NR 12 TC 46 Z9 56 U1 0 U2 0 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 USA SN 0278-4297 J9 J ULTRAS MED JI J. Ultrasound Med. PD NOV PY 2007 VL 26 IS 11 BP 1513 EP 1522 PG 10 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 227EH UT WOS:000250639500006 PM 17957045 ER PT J AU Huang, X Zhang, XP Farahvash, B Olumi, AF AF Huang, Xu Zhang, Xiaoping Farahvash, Benyamin Olumi, Aria F. TI Novel targeted pro-apoptotic agents for the treatment of prostate cancer SO JOURNAL OF UROLOGY LA English DT Review DE prostate; prostatic neoplasms; apoptosis; drug therapy; apoptosis regulatory proteins ID TRAIL-INDUCED APOPTOSIS; CELL-DEATH; IN-VIVO; ANTISENSE OLIGONUCLEOTIDE; ANTITUMOR-ACTIVITY; ANDROGEN RECEPTOR; INHIBITOR PS-341; INDUCE APOPTOSIS; CARCINOMA-CELLS; LIGAND TRAIL AB Purpose: We reviewed and highlighted novel targeted apoptotic mediated therapies that can be used to treat prostate cancer. Materials and Methods: A comprehensive review of the peer reviewed literature in the area of apoptosis was performed with special emphasis on apoptotic mediated pathways with promising novel targeted therapies that can be used for patients with prostate cancer. Results: The apoptotic pathway can be classified into 2 separate broad categories, including the extrinsic and the intrinsic pathways. Targeting the extrinsic or intrinsic mediated pathway holds promise for developing novel agents for treating prostate cancer. We discuss apoptosis related molecules and therapies, as categorized by 1) targeting apoptosis pathway for antitumor treatment, 2) targeting apoptosis regulators for antitumor treatment and 3) drugs that potentiate pro-apoptotic agents. Conclusions: Defining the molecules responsible for apoptosis and their intricate molecular interactions will help guide us in developing drugs with less toxicity for appropriately selected patients with prostate cancer and other malignancies. Because neoadjuvant and adjuvant clinical trials are under way using novel pro-apoptotic agents for prostate cancer, it is imperative for urologists to be active members of the clinical research team and become familiar with the molecular pathways, and potential benefits and toxicities associated with these novel agents. C1 Beth Israel Deaconess Med Ctr, Dept Urol Surg, Boston, MA 02215 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Urol Surg, Boston, MA 02114 USA. RP Olumi, AF (reprint author), Massachusetts Gen Hosp, Dept Urol, Yawkey Bldg,Suite 7E,55 Fruit St, Boston, MA 02114 USA. EM aolumi@partners.org FU NIDDK NIH HHS [DK64062] NR 50 TC 11 Z9 11 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD NOV PY 2007 VL 178 IS 5 BP 1846 EP 1854 DI 10.1016/j.juro.2007.06.039 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 220WC UT WOS:000250187000005 PM 17868738 ER PT J AU Motzer, RJ Michaelson, MD Rosenberg, J Bukowski, RM Curti, BD George, DJ Hudes, GR Redman, BG Margolin, KA Wilding, G AF Motzer, Robert J. Michaelson, M. Dror Rosenberg, Jonathan Bukowski, Ronald M. Curti, Brendan D. George, Daniel J. Hudes, Gary R. Redman, Bruce G. Margolin, Kim A. Wilding, George TI Sunitinib efficacy against advanced renal cell carcinoma SO JOURNAL OF UROLOGY LA English DT Article DE kidney; carcinoma; renal cell; sunitinib; neoplasm metastasis ID ENDOTHELIAL GROWTH-FACTOR; INTERFERON-ALPHA; RANDOMIZED-TRIAL; SURVIVAL; THERAPY; CANCER; INHIBITOR; SU11248 AB Purpose: We assessed the efficacy of the oral multitargeted tyrosine kinase inhibitor sunitinib in patients with metastatic clear cell renal cell carcinoma. Materials and Methods: Patients with metastatic clear cell renal cell carcinoma were enrolled in this multicenter, phase II clinical trial. Major eligibility requirements were clear cell renal cell carcinoma histology, prior nephrectomy, measurable metastases and failed prior cytokine therapy as a result of disease progression. Sunitinib was given orally as second line therapy in 6-week cycles of 50 mg daily for 4 weeks, followed by 2 weeks off drug per treatment cycle. Response to sunitinib was rigorously assessed by an independent third party core imaging laboratory (central review). Results: Of 106 patients enrolled in the study 105 were evaluated for response. As determined by independent third party assessment, the objective response rate was 33% (95% Cl 24%-43%) with a median response duration of 14.0 months. Median time to progression and median progression-free survival in the 105 evaluable patients was 10.7 and 8.8 months, respectively. Median survival was 23.9 months and 43 patients remained alive at a median followup of 29.7 months. Conclusions: The results of this trial demonstrate the efficacy of sunitinib for metastatic renal cell carcinoma. The optimal integration of surgery and sunitinib treatment requires further prospective investigation. C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. City Hope Natl Med Ctr, Duarte, CA 91010 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Earle A Chiles Res Inst, Portland, OR USA. Duke Univ, Med Ctr, Durham, NC USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Univ Wisconsin, Madison, WI USA. RP Motzer, RJ (reprint author), Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA. OI Michaelson, Dror/0000-0001-9249-6338 NR 18 TC 141 Z9 150 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD NOV PY 2007 VL 178 IS 5 BP 1883 EP 1887 DI 10.1016/j.juro.2007.07.030 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 220WC UT WOS:000250187000011 PM 17868732 ER PT J AU Escudier, B Choueiri, TK Oudard, S Szczylik, C Negrier, S Ravaud, A Chevreau, C Venner, P Champagne, P Croteau, D Dupont, E Hariton, C Bukowski, RM AF Escudier, Bernard Choueiri, Toni K. Oudard, Stephane Szczylik, Cezary Negrier, Sylvie Ravaud, Alain Chevreau, Christine Venner, Peter Champagne, Pierre Croteau, Daniel Dupont, Eric Hariton, Claude Bukowski, Ronald M. TI Prognostic factors of metastatic renal cell carcinoma after failure of immunotherapy: New paradigm from a large phase III trial with shark cartilage extract AE 941 SO JOURNAL OF UROLOGY LA English DT Article DE kidney; neoplasm metastasis; carcinoma; renal cell; prognosis; shark cartilage extract AE 941 ID LONG-TERM SURVIVAL; INTERFERON ALPHA-2A; RANDOMIZED-TRIAL; INTERLEUKIN-2; SUNITINIB; CANCER AB Purpose: We analyzed prognostic factors, described survival and generated a prognostic model in patients with metastatic renal cell carcinoma in whom immunotherapy failed and who were potentially eligible for novel agents. Materials and Methods: An analysis of the relationship between clinical features and survival was performed in 300 patients with advanced renal cell carcinoma in whom immunotherapy had failed and who were subsequently treated as part of a single, phase III clinical trial with the anti-angiogenic agent Neovastat (shark cartilage extract AE 941). Clinical features were first examined univariately and a stepwise modeling approach based on Cox proportional hazard regression was then performed to generate a multivariate model. Results: Median and progression-free survival (prognostic factors) for the whole cohort was 12.6 and 2 months, respectively. Prognostic features associated with shorter survival on multivariate analysis were the number of metastatic sites (greater than 1), time from nephrectomy to metastatic disease (less than 2 years), high alkaline phosphatase, abnormal corrected serum Ca and high lactate dehydrogenase (greater than 1.5 X the upper limit of normal). Four prognostic subgroups were identified by counting the number of adverse prognostic factors. Median survival in patients with zero adverse prognostic factors was 15.6 months compared to 11.7 months in patients with 1,8.5 months in patients with 2 and 3.5 months in patients with 3 or more. Conclusions: We identified 4 risk groups to predict survival in previously treated patients with renal cell carcinoma. This model was based on data from what is to our knowledge the largest experience in this population. It should be used in clinical trial design, risk stratification and patient counseling. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Inst Gustave Roussy, Villejuif, France. Hop Europeen Georges Pompidou, Paris, France. Ctr Leon Berard, F-69373 Lyon, France. Ctr Hosp Univ Bordeaux, Toulouse, France. Ctr Claudius Regaud, Toulouse, France. Cleveland Clin Taussig Canc Ctr, Cleveland, OH USA. Wojskowy Instytut Medyczny, Warsaw, Poland. Cross Canc Inst, Edmonton, AB T6G 1Z2, Canada. Eterna Labs Inc, Quebec City, PQ, Canada. RP Choueiri, TK (reprint author), Dana Farber Canc Inst, 44 Binney St,DANA 1230, Boston, MA 02115 USA. EM Toni_Choueiri@dfci.harvard.edu RI Chevreau, Christine/A-5565-2015 NR 20 TC 40 Z9 40 U1 2 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD NOV PY 2007 VL 178 IS 5 BP 1901 EP 1905 DI 10.1016/j.juro.2007.07.035 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 220WC UT WOS:000250187000017 PM 17868728 ER PT J AU Lin, PH Zhou, W Kougias, P El Sayed, HF Barshes, NR Huynh, TT AF Lin, Peter H. Zhou, Wei Kougias, Panagiotis El Sayed, Hosam F. Barshes, Neal R. Huynh, Tam T. TI Factors associated with hypotension and bradycardia after carotid angioplasty and stenting SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 31st Annual Meeting of the Southern-Association-for-Vascular-Surgery CY JAN 17-20, 2007 CL Rio Grande, PR SP So Assoc Vasc Surg ID HIGH-RISK PATIENTS; HEMODYNAMIC INSTABILITY; CLINICAL-OUTCOMES; CIGARETTE-SMOKING; ARTERY STENOSIS; BLOOD-PRESSURE; ENDARTERECTOMY; PREDICTORS; PREVENTION; PROTECTION AB Background: Acute procedurally induced hemodynamic depression can occur after carotid angioplasty and stenting (CAS). This study was performed to determine the frequency and risk factors for hypotension and bradycardia after the CAS procedure. Methods: The study reviewed clinical variables and angiographic data of all patients undergoing elective CAS with neuroprotection during a recent 5-year period. Intravenous atropine was given selectively in cases of bradycardia (heart rate <60 beats/min or a decrease of >20 beats/min). We further defined hemodynamic depression as bradycardia or severe hypotension (systolic blood pressure fall >30 turn Hg). Frequency and potential risk factors for hemodynamic depression were analyzed by logistic regression. Results: During the study period, 416 patients (99% male; mean age, 74 +/- 11 years) underwent the CAS procedure. The median degree of stenosis was 93% (range, 60% to 99%). The frequencies of post-CAS hemodynamic depression include hypotension in 58 (14%), bradycardia in 112 (27%), or both in 21 (5%). All patients with bradycardia received intraprocedural atropine, and all heart rates returned to the baseline level. Persistent hypotension occurred in 45 patients (11%). Increased age was associated with CAS-induced bradycardia or hypotension. Adjusted risk factors associated with hemodynamic depression include age >78 years (odds ratio [OR], 5.25; 95% confidence interval [CI], 2.32 to 15.25; P = .01) and ejection fraction of <25% (OR, 3.25; 95% CI, 0.58 to 6.58; P = .02). CEA-related restenosis was associated with a reduced risk of hemodynamic depression (OR, 0.21; 95% CI, 0.12 to 0.69, P = .001). Persistent hypotension after CAS was associated with an increased risk of an adverse clinical event (44%, P = .001). Conclusions: Hemodynamic depression, including hypotension and bradycardia, is frequent after CAS. However, CAS-induced hemodynamic depression is rare in patients with postendarterectomy stenosis. Patients with compromised ejection fraction and increased age are at a higher risk of presenting with CAS-induced hemodynamic instability, and persistent hypotension after CAS is associated with an increased postprocedural complication rate. C1 Baylor Coll Med, Dept Surg, Houston, TX 77030 USA. VA Med Ctr, Houston, TX USA. Baylor Coll Med, Div Vasc Surg & Endovasc Therapy, Houston, TX 77030 USA. RP Lin, PH (reprint author), Baylor Coll Med, Dept Surg, VAMC 112,2002 Holcomb Blvd, Houston, TX 77030 USA. EM plin@bcm.edu NR 35 TC 26 Z9 32 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD NOV PY 2007 VL 46 IS 5 BP 846 EP 854 DI 10.1016/j.jvs.2007.07.020 PG 9 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 227RO UT WOS:000250675700003 PM 17980268 ER PT J AU Trimarchi, S Tsai, T Eagle, KA Isselbacher, EM Froehlich, J Cooper, JV Rampoldi, V Upchurch, GR AF Trimarchi, Santi Tsai, Thomas Eagle, Kim A. Isselbacher, Eric M. Froehlich, Jim Cooper, Jeanna V. Rampoldi, Vincenzo Upchurch, Gilbert R., Jr. CA IRAD Investigators TI Acute abdominal aortic dissection: Insight from the international registry of acute aortic dissection (IRAD) SO JOURNAL OF VASCULAR SURGERY LA English DT Article; Proceedings Paper CT 35th Annual Meeting of the Society-for-Clinical-Vascular-Surgery CY MAR 21-24, 2007 CL Orlando, FL SP Soc Clin Vasc Surg ID MANAGEMENT; ANEURYSM AB Background: Isolated acute dissection of the abdominal aorta is an unusual event that may present with several different clinical scenarios. Because its incidence is low, the natural history is unknown. We report data from the International Registry of Acute Aortic Dissection (IRAD), the largest group of patients treated for acute aortic dissections. The aim of this study was to identify clinical characteristics, therapeutic approaches, risk factors for mortality, in-hospital outcome, and long-term results of this cohort, thus clarifying its natural history. Methods: A comprehensive analysis of 290 clinical variables on 18 patients affected by isolated acute abdominal aortic dissection (IAAAD) was performed. Among 1417 patients enrolled in the IRAD from 1996 to 2003, 532 (37.5%) had an acute type B dissection, of which 18 (1.3%) had an IAAAD. Theor mean age was 67.7 +/- 13.3 years, with a male predominance (n = 12, 67%). Aortic aneurysms pre-existed in 5 patients (28%). IAAAD was iatrogenic in 2 cases (11%). Results: Compared with patients with type B aortic dissections, abdominal pain, mesenteric ischemia or infarction, limb ischemia, and hypotension as initial clinical signs were significantly more frequent in patients with IAAAD, whereas chest pain was more typical in patients with type B dissections. No neurologic symptoms, such as ischemic spinal cord damage or ischemic peripheral neuropathy, occurred in the IAAAD cohort. The 18 IAAAD patients were medically, surgically, or percutaneously managed in 12 (66.6%), five (27.8%), and one (5.6%) cases, respectively. The overall in-hospital mortality rate was 5.6% (n = 1). The patient who died was medically managed. No deaths were reported among patients who underwent surgery or had an endovascular procedure, irrespective of their preoperative status. A mean follow-up of 5 years (range, 1 month to 9 years) was completed for 71% (12 of 17) of the patients. Four patients (33.3%) died during the 9-year follow-up period. Overall survival was 93.3% +/- 12.6% at 1 year and 73.3% +/- 27.2% at 5 years. All patients who died during the follow-up period had in-hospital medical management (P = .04). Conclusions: IAAAD is a condition that may present differently compared with classic type B aortic dissections. IAAAD patients treated with surgical or endovascular procedures had a lower unadjusted in-hospital and long-term mortality rate compared with medically managed patients. On the basis of the present natural history report, continued surveillance appears mandatory. To improve the life expectancy of patients with IAAAD, aggressive surgical or endovascular management seems justified. C1 Univ Milan, Cardiovasc Ctr E Malan, Policlin S Donato, IRCCS, I-20097 San Donato Milanese, Italy. Univ Michigan, Ann Arbor, MI 48109 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Trimarchi, S (reprint author), Univ Milan, Cardiovasc Ctr E Malan, Policlin S Donato, IRCCS, Via Morandi 30, I-20097 San Donato Milanese, Italy. EM satrimarchi@yahoo.it RI Trimarchi, Santi/J-7361-2016 OI Trimarchi, Santi/0000-0001-5996-3264 NR 21 TC 29 Z9 35 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD NOV PY 2007 VL 46 IS 5 BP 913 EP 919 DI 10.1016/j.jvs.2007.07.030 PG 7 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 227RO UT WOS:000250675700012 PM 17980278 ER PT J AU Kuntzen, T Timm, J Berical, A Lewis-Ximenez, LL Jones, A Nolan, B Wiesch, JSZ Li, B Schneidewind, A Kim, AY Chung, RT Lauer, GM Allen, TM AF Kuntzen, Thomas Timm, Joerg Berical, Andrew Lewis-Ximenez, Lia L. Jones, Andrea Nolan, Brian Wiesch, Julian Schulze zur Li, Bin Schneidewind, Arne Kim, Arthur Y. Chung, Raymond T. Lauer, Georg M. Allen, Todd M. TI Viral sequence evolution in acute hepatitis C virus infection SO JOURNAL OF VIROLOGY LA English DT Article ID CYTOTOXIC T-LYMPHOCYTES; CELLULAR IMMUNE-RESPONSES; ESCAPE MUTATIONS; FITNESS COST; LONG-TERM; IN-VIVO; TYPE-1; REVERSION; TRANSMISSION; SELECTION AB CD8(+)-T-cell responses play an important role in the containment and clearance of hepatitis C virus (HCV) infection, and an association between viral persistence and development of viral escape mutations has been postulated. While escape from CD8(+)-T-cell responses has been identified as a major driving force for the evolution of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV), a broader characterization of this relationship is needed in HCV infection. To determine the extent, kinetics, and driving forces of HCV sequence evolution, we sequenced the entire HCV genome longitudinally in four subjects monitored for up to 30 months after acute infection. For two subjects the transmission sources were also available. Of 53 total nonenvelope amino acid substitutions detected, a majority represented forward mutations away from the consensus sequence. In contrast to studies in HIV and SIV, however, only 11% of these were associated with detectable CD8(+) T-cell responses. Interestingly, 19% of nonenvelope mutations represented changes toward the consensus sequence, suggesting reversion in the absence of immune pressure upon transmission. Notably, the rate of evolution of forward and reverse mutations correlated with the conservation of each residue, which is indicative of structural constraints influencing the kinetics of viral evolution. Finally, the rate of sequence evolution was observed to decline over the course of infection, possibly reflective of diminishing selection pressure by dysfunctional CD8(+) T cells. Taken together, these data provide insight into the extent to which HCV is capable of evading early CD8(+) T-cell responses and support the hypothesis that dysfunction of CD8(+) T cells may be associated with failure to resolve HCV infections. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Infect Dis Div,Partners AIDS Res Ctr, Boston, MA USA. Univ Hosp Essen, Dept Virol, Essen, Germany. Inst Oswaldo Cruz Fiocruz, Dept Virol, Rio De Janeiro, Brazil. Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. RP Allen, TM (reprint author), Massachusetts Gen Hosp, Boston, MA 02129 USA. EM tallen2@partners.org RI Allen, Todd/F-5473-2011 FU NIAID NIH HHS [R01 AI 067926-01, R01 AI067926, U19 AI 066345-02, U19 AI066345] NR 53 TC 72 Z9 72 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 2007 VL 81 IS 21 BP 11658 EP 11668 DI 10.1128/JVI.00995-07 PG 11 WC Virology SC Virology GA 224AM UT WOS:000250417400013 PM 17699568 ER PT J AU Schneidewind, A Brockman, MA Yang, R Adam, RI Li, B Le Gall, S Rinaldo, CR Craggs, SL Allgaier, RL Power, KA Kuntzen, T Tung, CS LaBute, MX Mueller, SM Harrer, T McMichael, AJ Goulder, PJR Aiken, C Brander, C Kelleher, AD Allen, TM AF Schneidewind, Arne Brockman, Mark A. Yang, Ruifeng Adam, Rahma I. Li, Bin Le Gall, Sylvie Rinaldo, Charles R. Craggs, Sharon L. Allgaier, Rachel L. Power, Karen A. Kuntzen, Thomas Tung, Chang-Shung LaBute, Montiago X. Mueller, Sandra M. Harrer, Thomas McMichael, Andrew J. Goulder, Philip J. R. Aiken, Cbristopher Brander, Christian Kelleher, Anthony D. Allen, Todd M. TI Escape from the dominant HLA-B27-restricted cytotoxic T-lymphocyte response in gag is associated with a dramatic reduction in human immunodeficiency virus type 1 replication SO JOURNAL OF VIROLOGY LA English DT Article ID OWL MONKEY CELLS; CLASS-I ALLELES; CYCLOPHILIN-A; HIV-1 INFECTION; VIRAL LOAD; HOST RESTRICTION; VACCINE DESIGN; CYCLOSPORINE-A; P24 GAG; REVERSION AB Human leukocyte antigen (HLA)-B27-positive subjects are uncommon in their ability to control infection with human immunodeficiency virus type 1 (HIV-1). However, late viral escape from a narrowly directed immunodominant Gag-specific CD8(+) T-lymphocyte (CTL) response has been linked to AIDS progression in these individuals. Identifying the mechanism of the immune-mediated control may provide critical insights into HIV-1 vaccine development. Here, we illustrate that the CTL escape mutation R264K in the HLA-B27-restricted KK10 epitope in the capsid resulted in a significant defect in viral replication in vitro. The R264K variant was impaired in generating late reverse transcription products, indicating that replication was blocked at a postentry step. Notably, the R264K mutation was associated in vivo with the development of a rare secondary mutation, S(173)A, which restored viral replication in vitro. Furthermore, infectivity of the R264K variant was rescued by the addition of cyclosporine A or infection of a cyclophilin A-deficient cell line. These data demonstrate a severe functional defect imposed by the R264K mutation during an early step in viral replication that is likely due to the inability of this variant to replicate efficiently in the presence of normal levels of cyclophilin A. We conclude that the impact of the R264K substitution on capsid structure constrains viral escape and enables long-term maintenance of the dominant CTL response against B27-KK10, providing an explanation for the protective effect of HLA-B27 during HIV infection. C1 [Schneidewind, Arne; Brockman, Mark A.; Adam, Rahma I.; Li, Bin; Le Gall, Sylvie; Allgaier, Rachel L.; Power, Karen A.; Kuntzen, Thomas; Goulder, Philip J. R.; Brander, Christian; Allen, Todd M.] Harvard Univ, Sch Med, Partners AIDS Res Ctr, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Brockman, Mark A.] Harvard Univ, Sch Med, Howard Hughes Med Inst, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Yang, Ruifeng; Aiken, Cbristopher] Vanderbilt Univ, Dept Microbiol & Immunol, Sch Med, Med Ctr N A 5301, Nashville, TN USA. [Rinaldo, Charles R.] Univ Pittsburgh, Dept Pathol, Sch Med, Pittsburgh, PA USA. [Craggs, Sharon L.; McMichael, Andrew J.] John Radcliffe Hosp, Weatherall Inst Mol Med, MRC Human Immunol Unit, Oxford OX3 9DU, England. [Tung, Chang-Shung; LaBute, Montiago X.] Los Alamos Natl Lab, Div Theoret, Los Alamos, NM USA. [Mueller, Sandra M.; Harrer, Thomas] Univ Erlangen Nurnberg, Inst Clin & Mol Virol, Erlangen, Germany. [Goulder, Philip J. R.] Peter Medawar Bldg Pathogen Res, Nuffield Dept Med, Dept Pediat, Oxford, England. [Kelleher, Anthony D.] Univ New S Wales, Natl Ctr HIV Epidemiol & Clin Res, Sydney, NSW, Australia. RP Allen, TM (reprint author), MGH-E,CNY 6625 149 13th St, Hillsborough 02129, North Ireland. EM tallen2@partners.org RI Allen, Todd/F-5473-2011; OI Brander, Christian/0000-0002-0548-5778; Brockman, Mark/0000-0001-6432-1426 FU Medical Research Council [MC_U137884177]; NIAID NIH HHS [R01 AI050423, R01 AI054178, R21 AI067078, U01 AI052403] NR 80 TC 220 Z9 225 U1 1 U2 9 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 2007 VL 81 IS 22 BP 12382 EP 12393 DI 10.1128/JVI.01543-07 PG 12 WC Virology SC Virology GA 275IP UT WOS:000254065400029 PM 17804494 ER PT J AU Brockman, MA Schneidewind, A Lahaie, M Schmidt, A Miura, T DeSouza, I Ryvkin, F Derdeyn, CA Allen, S Hunter, E Mulenga, J Goepfert, PA Walker, BD Allen, TM AF Brockman, Mark A. Schneidewind, Arne Lahaie, Matthew Schmidt, Aaron Miura, Toshiyuki DeSouza, Ivna Ryvkin, Faina Derdeyn, Cynthia A. Allen, Susan Hunter, Eric Mulenga, Joseph Goepfert, Paul A. Walker, Bruce D. Allen, Todd M. TI Escape and compensation from early HLA-B57-Mediated cytotoxic T-lymphocyte pressure on human immunodeficiency virus type 1 Gag alter capsid interactions with cyclophilin A SO JOURNAL OF VIROLOGY LA English DT Article ID STRUCTURALLY CONSTRAINED EPITOPE; LONG-TERM NONPROGRESSORS; REPORTER CELL-LINE; HIV-1 INFECTION; IMMUNE-RESPONSES; VIRAL ESCAPE; SUBTYPE-C; GROUP-O; REPLICATION; HLA AB Certain histocompatibility leukocyte antigen (HLA) alleles are associated with improved clinical outcomes for individuals infected with human immunodeficiency virus type 1 (HIV-1), but the mechanisms for their effects remain undefined. An early CD8(+) T-cell escape mutation in the dominant HLA-B57-restrieted Gag epitope TW10 (TSTLQEQIGW) has been shown to impair HIV-1 replication capacity in vitro. We demonstrate here that this T242N substitution in the capsid protein is associated with upstream mutations at residues H-219, I-223, and M-228 in the cyclophilin A (CypA)-binding loop in B57(+) individuals with progressive disease. In an independent cohort of epidemiologically linked transmission pairs, the presence of these substitutions in viruses encoding T242N was associated with significantly higher plasma viremia in donors, further suggesting that these secondary mutations compensated for the replication defect of T242N. Using NL4-3 constructs, we illustrate the ability of these CypA loop changes to partially restore replication of the T242N variant in vitro. Notably, these mutations also enhanced viral resistance to the drug cyclosporine A, indicating a reduced dependence of the compensated virus on CypA that is normally essential for optimal infectivity. Therefore, mutations in TW10 allow HIV-1 to evade a dominant early CD8(+) T-cell response, but the benefits of escape are offset by a defect in capsid function. These data suggest that TW10 escape variants undergo a postentry block that is partially overcome by changes in the CypA-binding loop and identify a mechanism for an HIV-1 fitness defect that may contribute to the slower disease progression associated with HLA-B57. C1 [Brockman, Mark A.; Schneidewind, Arne; Lahaie, Matthew; Schmidt, Aaron; Miura, Toshiyuki; DeSouza, Ivna; Walker, Bruce D.; Allen, Todd M.] Massachusetts Gen Hosp East, Partners AIDS Res Ctr, Charlestown, MA 02129 USA. [Brockman, Mark A.; Miura, Toshiyuki; Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD USA. [Schmidt, Aaron; Ryvkin, Faina] Univ Cambridge Emmanuel Coll, Dept Biol, Boston, MA USA. [Schmidt, Aaron; Ryvkin, Faina] Univ Cambridge Emmanuel Coll, Dept Chem, Boston, MA USA. [Derdeyn, Cynthia A.; Hunter, Eric] Emory Univ, Emory Vaccine Ctr, Atlanta, GA 30322 USA. [Allen, Susan; Mulenga, Joseph] Zambia Blood Transfus Serv, Zambia Emory HIV Res Grp, Lusaka, Zambia. [Goepfert, Paul A.] Univ Alabama Birmingham, Birmingham, AL USA. RP Allen, TM (reprint author), Massachusetts Gen Hosp East, Partners AIDS Res Ctr, CNY 6625,149 13th St, Charlestown, MA 02129 USA. EM tallen2@partners.org RI Allen, Todd/F-5473-2011; OI Brockman, Mark/0000-0001-6432-1426 FU NIAID NIH HHS [R01 AI054178, R01 AI64030, R21 AI067078, R01 AI028568] NR 68 TC 182 Z9 185 U1 2 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD NOV PY 2007 VL 81 IS 22 BP 12608 EP 12618 DI 10.1128/JVI.01369-07 PG 11 WC Virology SC Virology GA 275IP UT WOS:000254065400051 PM 17728232 ER PT J AU Yu, XG Lichterfeld, M Williams, KL Martinez-Picado, J Walker, BD AF Yu, Xu G. Lichterfeld, Mathias Williams, Katie L. Martinez-Picado, Javier Walker, Bruce D. TI Random T-cell receptor recruitment in human immunodeficiency virus type 1 (HIV-1)-specific CD8(+) T cells from genetically identical twins infected with the same HIV-1 strain SO JOURNAL OF VIROLOGY LA English DT Article ID CLASS-I; ESCAPE; IMMUNODOMINANCE; RESPONSES AB Human immunodeficiency virus type 1 (HIV-1) cytotoxic T-lymphocyte escape mutations represent both a major reason for loss of HIV immune control and a considerable challenge for HIV-1 vaccine design. Previous data suggest that initial HIV-1-specific CD8(+) T-cell responses are determined largely by viral and host genetics, but the mechanisms influencing the subsequent viral evolution are unclear. Here, we show a random recruitment of T-cell receptor (TCR) alpha and beta clonotypes of the initial HIV-1-specific CD8(+) T cells during primary infection in two genetically identical twins infected simultaneously with the same virus, suggesting that stochastic TCR recruitment of HIV-1-specific CD8(+) T cells contributes to the diverse and unpredictable HIV-1 sequence evolution. C1 [Yu, Xu G.; Lichterfeld, Mathias; Williams, Katie L.; Walker, Bruce D.] Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA 02129 USA. [Martinez-Picado, Javier] Hosp Univ Germans Trias & Pujol, Fundacio irsiCaixa, Barcelona, Spain. [Martinez-Picado, Javier] ICREA, Barcelona, Spain. [Walker, Bruce D.] Howard Hughes Med Inst, Chevy Chase, MD USA. RP Walker, BD (reprint author), Massachusetts Gen Hosp, Partners AIDS Res Ctr, 149 13th St,Room 5212, Charlestown, MA 02129 USA. EM bwalker@partners.org RI Martinez-Picado, Javier/G-5507-2012 OI Martinez-Picado, Javier/0000-0002-4916-2129 NR 9 TC 13 Z9 13 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD NOV PY 2007 VL 81 IS 22 BP 12666 EP 12669 DI 10.1128/JVI.01450-07 PG 4 WC Virology SC Virology GA 275IP UT WOS:000254065400056 PM 17804503 ER PT J AU Bean-Mayberry, B Yano, EM Bayliss, N Navratil, J Weisman, CS Scholle, SH AF Bean-Mayberry, Bevanne Yano, Elizabeth M. Bayliss, Nichole Navratil, Judith Weisman, Carol S. Scholle, Sarah Hudson TI Federally funded comprehensive women's health centers: Leading innovation in women's healthcare delivery SO JOURNAL OF WOMENS HEALTH LA English DT Article ID AFFAIRS MEDICAL-CENTER; QUALITY-OF-CARE; NATIONAL CENTERS; EXCELLENCE; SYSTEM AB Aims: Women's healthcare has historically been fragmented, given the artificial separation of reproductive care from general medical care. Aiming to advance new care models for delivery of comprehensive, integrated clinical care for women, two federal agencies-the U. S. Department of Health and Human Services (DHHS) and Department of Veterans Affairs (VA)-launched specialized women's health centers (WHCs). Exemplars of comprehensive service delivery, these originally federally funded centers have served as foundations for innovations in delivering comprehensive care to women in diverse practice settings. Little is known, however, about details of their organization, staffing, practice arrangements, and service availability that might inform adoption of similar models in the community. Methods: Using comparable key informant surveys, we collected organizational data from the DHHS National Centers of Excellence (CoE) (n = 13) and the original VA comprehensive WHC's (n = 8). We abstracted supplemental data (e. g., academic affiliation) from the 2001 American Hospital Association (AHA) survey. Results: All DHHS and VA women's health programs served urban areas, and nearly all had academic partnerships. DHHS centers had three times the average caseload as did VA centers. Preventive cancer screening and general reproductive services were uniformly available at all centers, although DHHS centers offered extensive reproductive services on-site more frequently, and VA centers more often had on-site mental healthcare. Conclusions: The DHHS and VA comprehensive WHCs share similar missions and comparable organization, education, and clinical services, demonstrating their commitment to reducing fragmented service delivery. Their common structural components present opportunities for further advancing women's quality of care across other systems of care. C1 VA Greater Los Angeles Healthcare Syst, VA HSR&D Ctr Excellence Study Healthcare Provider, Sepulveda, CA 91343 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Hlth Serv, Los Angeles, CA 90024 USA. VA Pittsburgh Healthcare Syst, CHERP, Pittsburgh, PA USA. Univ Pittsburgh, Dept Sociol, Pittsburgh, PA USA. Univ Pittsburgh, Western Psychiat Inst & Clin, Dept Psychiat, Pittsburgh, PA 15213 USA. Penn State Univ, Coll Med, Dept Hlth Evaluat Sci, Hershey, PA USA. Penn State Univ, Coll Med, Dept Obstet & Gynaecol, Hershey, PA USA. Natl Comm Qual Assurance Res & Anal, Washington, DC USA. RP Bean-Mayberry, B (reprint author), VA Greater Los Angeles Healthcare Syst, VA HSR&D Ctr Excellence Study Healthcare Provider, 16111 Plummer St,Mailcode 152, Sepulveda, CA 91343 USA. EM Bevanne.bean-mayberry@va.gov NR 26 TC 23 Z9 23 U1 0 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD NOV PY 2007 VL 16 IS 9 BP 1281 EP 1290 DI 10.1089/jwh.2006.0284 PG 10 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 234PB UT WOS:000251174900005 PM 18001184 ER PT J AU Russo, LM Sandoval, RM Brown, D Molitoris, BA Comper, WD AF Russo, L. M. Sandoval, R. M. Brown, D. Molitoris, B. A. Comper, W. D. TI Controversies in nephrology: Response to 'renal albumin handling, facts, and artifacts' SO KIDNEY INTERNATIONAL LA English DT Review DE glomerular charge; albumin transcytosis; albumin retrieval ID GLOMERULAR BARRIER; KIDNEY ULTRAFILTRATION; FRACTIONAL CLEARANCE; CHARGE SELECTIVITY; DEXTRAN SULFATE; FILTRATION-RATE; PROTEINS; INCREASE AB For 40 years indirect measurements of the glomerular sieving coefficient of albumin yielded very low values. The first direct measurement by 2-photon microscopy by Russo et al (Kidney Int (2007) 71, 504-513) gives values 50-times higher. This demonstrated that relatively large quantities of albumin are normally filtered based on size selectivity alone. Most of this albumin is retrieved and returned to the blood supply. These new discoveries represent a paradigm shift in our understanding of albumin processing by the kidney. They also serve to explain several anomalous aspects of previous studies on glomerular filtration and mechanism of albuminuria and support the fact that glomerular charge selectivity is not a major factor controlling glomerular permselectivity. C1 Monash Univ, Dept Biochem & Mol Biol, Clayton, Vic 3800, Australia. Massachusetts Gen Hosp, Renal Unit, Program Membrane Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. Indiana Univ, Sch Med, Indiana Ctr Biol Microscopy, Indianapolis, IN USA. RP Comper, WD (reprint author), Monash Univ, Dept Biochem & Mol Biol, Clayton, Vic 3800, Australia. EM wcomper@hotmail.com NR 21 TC 19 Z9 19 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD NOV PY 2007 VL 72 IS 10 BP 1195 EP 1197 DI 10.1038/sj.ki.5002528 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 229DW UT WOS:000250784200011 PM 17851467 ER PT J AU Faber, J Armstrong, SA AF Faber, J. Armstrong, S. A. TI Defining laukemia stem cells in MLL-translocated laukemias: Implications for novel therapeutic strategies SO KLINISCHE PADIATRIE LA English DT Review DE mixed-lineage leukemia; leukemia stem cells; targeted therapy ID ACUTE LYMPHOBLASTIC-LEUKEMIA; ACUTE MYELOID-LEUKEMIA; GENE-EXPRESSION SIGNATURES; GEMTUZUMAB OZOGAMICIN; INTERFERING RNAS; INITIATING CELLS; BCR-ABL; IN-VIVO; CANCER; IDENTIFICATION AB Hematological malignancies and probably many other tumors are dependent on highly proliferating and self-renewing cancer stem cells. An important question in the development of novel, less toxic antileukemic strategies specifically targeting leukemia stem cells is how closely leukemia stem cells are related to normal hematopoietic stem cells. It has been recently demonstrated that leukemia stem cells can be derived from different stages in normal hematopoiesis and have unique phenotypic and genetic features. Introduction of Mixed-lineage leukemia (MLL)-fusion oncoproteins, frequently found in infant leukemias and therapy-related leukemias, into differentiated hematopoietic progenitor cells results in the generation of leukemias with a high frequency of leukemia stem cells. The progenitor-derived leukemia stem cells ectopically express a limited stem cell program while maintaining the global identity of differentiated myeloid cells. Development of therapeutic strategies that specifically target the leukemia stem cell program while sparing normal hematopoietic stem cells may represent a novel therapeutic approach in human leukemias with high efficacy yet less side effects. C1 Childrens Hosp, Harvard Med Sch, Dana Farber Canc Inst, Div Hematol Oncol,Dept Pediat Oncol, Boston, MA USA. RP Armstrong, SA (reprint author), Childrens Hosp Boston, Karp Family Res Labs, 1 Blackfan Circle Boston, Boston, MA 02115 USA. EM Scott.Armstrong@childrens.harvard.edu RI Faber, Joerg/G-4549-2010 NR 62 TC 6 Z9 6 U1 0 U2 2 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0300-8630 J9 KLIN PADIATR JI Klinische Padiatr. PD NOV-DEC PY 2007 VL 219 IS 6 BP 306 EP 311 DI 10.1055/s-2007-985878 PG 6 WC Pediatrics SC Pediatrics GA 239GM UT WOS:000251506800002 PM 18050039 ER PT J AU Lum, G AF Lum, Gifford TI Lithium self-intoxication treated with Hemodialysis SO LABMEDICINE LA English DT Editorial Material AB Lithium is widely used to treat bipolar affective disorders, but it has a narrow therapeutic window (0.6 to 1.2 mmol/L), and lithium toxicity often accompanies its use. This patient had acute, severe lithium intoxication (4.3 mmol/L) as a result of self-intoxication. He was successfully treated with hemodialysis, which is considered to be the most effective method for eliminating this drug. After 1 cycle of hemodialysis, the lithium levels returned to therapeutic concentrations (<1.0 mmol/L). C1 VA Boston Healthcare Syst, Pathol & Lab Med Serv, Boston, MA USA. RP Lum, G (reprint author), VA Boston Healthcare Syst, Pathol & Lab Med Serv, Boston, MA USA. NR 7 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0007-5027 J9 LABMEDICINE JI Labmedicine PD NOV PY 2007 VL 38 IS 11 BP 667 EP 668 DI 10.1309/CGA4FKTUDK2JWF46 PG 2 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 225UH UT WOS:000250543000007 ER PT J AU Rixe, O Bukowski, RM Michaelson, MD Wilding, G Hudes, GR Bolte, O Motzer, RJ Bycott, P Liou, KF Freddo, J Trask, PC Kim, S Rini, BI AF Rixe, Olivier Bukowski, Ronald M. Michaelson, M. Dror Wilding, George Hudes, Gaty R. Bolte, Oliver Motzer, Robert J. Bycott, Paul Liou, Katherine F. Freddo, James Trask, Peter C. Kim, Sinil Rini, Brian I. TI Axitinib treatment in patients with cytokine-refractory metastatic renal-cell cancer: a phase II study SO LANCET ONCOLOGY LA English DT Article ID SOLID TUMORS; CARCINOMA; SURVIVAL; TRIAL; VEGF; INHIBITOR; THERAPY; AGENT AB Background Axitinib (AG-013736) is an oral, potent, and selective inhibitor of vascular endothelial growth factor receptors 1, 2, and 3. We aimed to assess the activity and safety of axitinib in patients with metastatic renal-cell cancer who had failed on previous cytokine-based treatment. Methods Between Oct 3, 2003, and April 7, 2004, 52 patients were enrolled. All patients who had at least one measurable target lesion received axitinib orally (starting dose 5 mg twice daily). The primary endpoint was objective response (ie, percentage of patients with confirmed complete response or partial response by use of Response Evaluation Criteria In Solid Tumors [RECIST] criteria. Secondary endpoints were duration of response, time to progression, overall survival, safety, pharmacokinetics, and patient-reported health-related quality of life. This trial is registered on the clinical trials site of the US National Cancer Institute website http://www.clinicaltrials.gov/ct/show/ NCT00076011. Findings In an intention-to-treat analysis, two complete and 21 partial responses were noted, for an objective response rate of 44.2% (95% CI 30.5-58.7). Median response duration was 23.0 months (20.9-not estimable; range 4.2-29.8). However, 12 of 23 initial responders progressed with response duration ranging from 4.2 months to 26.5 months. Additionally, 22 patients showed stable disease for longer than 8 weeks, including 13 patients with stable disease for 24 weeks or longer. Four patients had early disease progression. Three patients had missing response data. Median time to progression was 15.7 months (8.4-23.4, range 0.03-31.5) and median overall survival was 29.9 months (20.3-not estimable; range 2.4-35.8). Treatment-related adverse events included diarrhoea, hypertension, fatigue, nausea, and hoarseness. Treatment-related hypertension occurred in 30 patients and resolved with antihypertensive treatment in all but eight patients, of whom seven patients had a history of hypertension at baseline. Interpretation Axitinib shows clinical activity in patients with cytokine-refractory metastatic renal-cell cancer. Although 28 patients had grade 3 or grade 4 treatment-related adverse events, these adverse events were generally manageable and controlled by dose modification or supportive care, or both. Further studies are needed to confirm these findings. C1 Univ Paris, Hop La Pitie Salpetriere, Paris, France. Cleveland Clin, Taussig Canc Ctr, Cleveland, OH USA. Massachusetts Gen Hosp, Boston, MA USA. Univ Wisconsin, Madison, WI 53706 USA. Fox Chase Canc Ctr, Philadelphia, PA USA. Hannover Med Sch, Hannover, Germany. Mem Sloan Kettering Canc Ctr, New York, NY USA. Pfizer Global Res & Dev, La Jolla, CA USA. Pfizer, New London, CT USA. RP Rixe, O (reprint author), Hop La Pitie Salpetriere, Med Canc Serv, 47-83 Blvd Hop, F-75651 Paris, France. EM olivier.rixe@psl.ap-hop-paris.fr NR 18 TC 304 Z9 322 U1 1 U2 16 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1470-2045 J9 LANCET ONCOL JI Lancet Oncol. PD NOV PY 2007 VL 8 IS 11 BP 975 EP 984 DI 10.1016/51470-2045(07)70285-1 PG 10 WC Oncology SC Oncology GA 230WP UT WOS:000250907300017 PM 17959415 ER PT J AU Du, YP Chu, R Hwang, D Brown, MS Kleinschmidt-DeMasters, BK Singel, D Simon, JH AF Du, Yiping P. Chu, Renxin Hwang, Dosik Brown, Mark S. Kleinschmidt-DeMasters, Bette K. Singel, Debra Simon, Jack H. TI Fast multislice mapping of the myelin water fraction using multicompartment analysis of T-2* decay at 3T: A preliminary postmortem study SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE myelin water fraction; multicompartment analysis; demyelination; multiple sclerosis; postmortem ID IN-VIVO MEASUREMENT; MULTIPLE-SCLEROSIS; WHITE-MATTER; MAGNETIC-RESONANCE; BRAIN; T-2; RELAXATION; MODEL; REDUCTION; COMPONENT AB Quantitative mapping of the myelin water content can provide significant insight into the pathophysiology of several white matter diseases, such as multiple sclerosis and leukoencephalopathies, and can potentially become a useful clinical tool for early diagnosis of these diseases. In this study, multicompartment analysis of T-2(*) decay (MCAT2(*)) was used for the quantitative mapping of myelin water fraction (MWF). T-2(*) decay of each voxel at multiple slice locations was acquired in fixed human brains using a multigradient-echo (MGRE) pulse sequence with alternating readout gradient polarities. Compared to prior techniques using Carr-Purcell-Meiboom-Gill (CPMG) acquisition, the MGRE acquisition approach has: 1) a very short first echo time (approximate to 2 ms) and echo-spacing (approximate to 1 ms), which allows for the acquisition of multiple sampling points during the fast decay of the myelin water signal; 2) a low RF duty cycle, which is especially important for achieving acceptable specific absorption rate (SAR) levels at high field strengths. Multicompartment analysis was then applied to the T-2(*) decay in each pixel using a 3-pool model of white matter to detect the signal arising from the myelin water, myelinated axonal water, and mixed water compartments. C1 Univ Colorado, Hlth Sci Ctr, Dept Radiol, Aurora, CO 80010 USA. Univ Colorado, Hlth Sci Ctr, Dept Pathol, Aurora, CO 80010 USA. Univ Colorado, Hlth Sci Ctr, Dept Neurol, Aurora, CO 80010 USA. Univ Colorado, Hlth Sci Ctr, Dept Neurosurg, Aurora, CO 80010 USA. Portland VA Med Ctr, Dept Imaging, Portland, OR USA. RP Du, YP (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Psychiat, Bldg 400,12469 E 17th Pl, Aurora, CO 80010 USA. EM Yiping.Du@UCHSC.edu NR 18 TC 55 Z9 55 U1 0 U2 5 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD NOV PY 2007 VL 58 IS 5 BP 865 EP 870 DI 10.1002/mrm.21409 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 226AQ UT WOS:000250560000002 PM 17969125 ER PT J AU Stanton, VA Hsieh, YH Camargo, CA Edlow, JA Lovett, P Goldstein, JN Abbuhl, S Lin, M Chanmugam, A Rothman, RE Newman-Toker, DE AF Stanton, Victoria A. Hsieh, Yu-Hsiang Camargo, Carlos A., Jr. Edlow, Jonathan A. Lovett, Paris Goldstein, Joshua N. Abbuhl, Stephanie Lin, Michelle Chanmugam, Arjun Rothman, Richard E. Newman-Toker, David E. TI Overreliance on symptom quality in diagnosing dizziness: Results of a Multicenter survey of emergency physicians SO MAYO CLINIC PROCEEDINGS LA English DT Article; Proceedings Paper CT Research Forum of the American-College-of-Emergency-Physicians CY OCT 08-09, 2007 CL Seattle, WA SP Amer Coll Emergency Phys ID PAROXYSMAL POSITIONAL VERTIGO; CEREBELLAR INFARCTION; DIZZY PATIENT; VERTEBRAL ARTERY; CEREBROVASCULAR-DISEASE; VESTIBULAR NEURITIS; MEDICAL PATIENTS; CHARTED RECORDS; COMMON SYMPTOMS; DISSECTION AB OBJECTIVE: To assess emergency physicians' diagnostic approach to the patient with dizziness, using a multicenter quantitative survey. PARTICIPANTS AND METHODS: We anonymously surveyed attending and resident emergency physicians at 17 academic-affiliated emergency departments with an Internet-based survey (September 1, 2006, to November 3, 2006). The survey respondents ranked the relative importance of symptom quality, timing, triggers, and associated symptoms and indicated their agreement with 20 statements about diagnostic assessment of dizziness (Likert scale). We used logistic regression to assess the impact of "symptom quality ranked first" on odds of agreement with diagnostic statements; we then stratified responses by academic rank. RESULTS: Of the 505 individuals surveyed, 415 responded for an overall response rate of 82%. A total of 93% (95% confidence interval [CI], 90%-95%) agreed that determining type of dizziness is very important, and 64% (95% CI, 60 /"-69%) ranked symptom quality as the most important diagnostic feature. In a multivariate model, those ranking quality first (particularly resident physicians) more often reported high-risk reasoning that might predispose patients to misdiagnosis (eg, in a patient with persistent, continuous dizziness, who could have a cerebellar stroke, resident physicians reported feeling reassured that a normal head computed tomogram indicates that the patient can safely go home) (odds ratio, 6.74; 95% CI, 2.05-22.19). CONCLUSION: Physicians report taking a quality-of-symptoms approach to the diagnosis of dizziness in patients in the emergency department. Those relying heavily on this approach may be predisposed to high-risk downstream diagnostic reasoning. Other clinical features (eg, timing, triggers, associated symptoms) appear relatively undervalued. Educational initiatives merit consideration. C1 Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. Univ Calif San Francisco, Sch Med, San Francisco, CA 94143 USA. Johns Hopkins Univ Hosp, Dept Emergency Med, Baltimore, MD 21287 USA. Johns Hopkins Univ Hosp, Dept Neurol, Baltimore, MD 21287 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Emergency Med, Cambridge, MA 02138 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Emergency Med, Cambridge, MA 02138 USA. Columbia Univ, Med Ctr, New York Presbyterian Hosp, Dept Emergency Med, New York, NY USA. Univ Penn, Sch Med, Dept Emergency Med, Philadelphia, PA 19104 USA. Univ Calif San Francisco, San Francisco Gen Hosp, Emergency Serv, San Francisco, CA 94143 USA. RP Newman-Toker, DE (reprint author), Johns Hopkins Univ Hosp, Pathol Bldg 2-210,600 N Wolfe St, Baltimore, MD 21287 USA. EM toker@jhu.edu RI Newman-Toker, David/C-6083-2008; Goldstein, Joshua/H-8953-2016; OI Newman-Toker, David/0000-0003-2789-4115; Rothman, Richard/0000-0002-1017-9505 FU NCRR NIH HHS [K23 RR17324-01] NR 67 TC 53 Z9 55 U1 0 U2 2 PU MAYO CLINIC PROCEEDINGS PI ROCHESTER PA 660 SIEBENS BLDG MAYO CLINIC, ROCHESTER, MN 55905 USA SN 0025-6196 J9 MAYO CLIN PROC JI Mayo Clin. Proc. PD NOV PY 2007 VL 82 IS 11 BP 1319 EP 1328 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 227CC UT WOS:000250633800004 PM 17976351 ER PT J AU Lesser, IM Castro, DB Gaynes, BN Gonzalez, J Rush, AJ Alpert, JE Trivedil, M Luther, JF Wisniewski, SR AF Lesser, Ira M. Castro, Daniel B. Gaynes, Bradley N. Gonzalez, Jodi Rush, A. John Alpert, Jonathan E. Trivedil, Madhukar Luther, James F. Wisniewski, Stephen R. TI Ethnicity/Race and outcome in the treatment of depression - Results from STAR*D SO MEDICAL CARE LA English DT Article DE depression; ethnicity; race; antidepressants; citalopram; treatment outcomes ID PRIMARY-CARE PATIENTS; ILLNESS RATING-SCALE; REPORT QIDS-SR; MINORITY PATIENTS; MAJOR DEPRESSION; PSYCHOMETRIC EVALUATION; PSYCHIATRIC-DISORDERS; ANXIETY DISORDERS; MEXICAN-AMERICANS; AFRICAN-AMERICAN AB Objectives: This secondary analysis of data from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study compared rates of remission and response for blacks (n = 495), whites (n = 1853), and Hispanics (n = 327) with nonpsychotic major depressive disorder who were treated with citalopram. Methods: STAR*D included representative outpatients treated in 23 psychiatric and 18 primary care centers. Participants received flexible doses of citalopram for up to 14 weeks, with dosage adjustments based on routine clinical assessments. Efforts were made to achieve remission, using a measurement-based care approach with adjustments based on symptoms and side effects assessed at each visit. Results: There were significant differences among groups on many baseline demographic, sociocultural, and clinical variables. Blacks and Hispanics were more socially disadvantaged and bad more comorbidity than whites. Before adjusting for differences, blacks had lower remission rates than whites, with Hispanics intermediate between the 2. After adjustments, remission rates for groups were not significantly different on the 17-item Hamilton Rating Scale for Depression (HRSD), but remained lower for blacks compared with whites with the 16-item Quick Inventory of Depressive Symptom-atology-Self Report (QIDS-SR). Blacks took longer to achieve remission or response, though this did not remain after adjusting for baseline differences. Conclusions: Overall, black and to a lesser extent Hispanic participants had a poorer response to citalopram. After adjusting for baseline differences, the remission rates seemed to be more similar on the HRSD, but remained worse for blacks on the QIDS-SR. We discuss the possible biologic and sociocultural factors that may underlie these findings. C1 Univ Calif Los Angeles, Harbor Med Ctr, Dept Psychiat, Los Angeles Biomed Res Inst Harbor, Torrance, CA 90509 USA. Univ Calif Los Angeles, Harbor Med Ctr, Dept Family Med, Los Angeles Biomed Res Inst Harbor, Harbor City, CA USA. Univ N Carolina, Chapel Hill Sch Med, Dept Psychiat, Chapel Hill, NC USA. Univ Texas, Hlth Sci Ctr, Dept Psychiat, San Antonio, TX 78284 USA. Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX USA. Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA. RP Lesser, IM (reprint author), Univ Calif Los Angeles, Harbor Med Ctr, Dept Psychiat, Los Angeles Biomed Res Inst Harbor, 1000 W Carson St,Box 8, Torrance, CA 90509 USA. EM liesser@Iadhs.org OI Wisniewski, Stephen/0000-0002-3877-9860; Alpert, Jonathan/0000-0002-4332-908X; Gaynes, Bradley/0000-0002-8283-5030; Rush, Augustus/0000-0003-2004-2382 FU NIMH NIH HHS [N01 MH 90003] NR 50 TC 37 Z9 37 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD NOV PY 2007 VL 45 IS 11 BP 1043 EP 1051 PG 9 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 227EI UT WOS:000250639600006 PM 18049344 ER PT J AU Polsky, D Lave, J Klusaritz, H Jha, A Pauly, MV Cen, L Xie, H Stone, R Chen, Z Volpp, K AF Polsky, Daniel Lave, Judith Klusaritz, Heather Jha, Ashish Pauly, Mark V. Cen, Liyi Xie, Hu Stone, Roslyn Chen, Zhen Volpp, Kevin TI Is lower 30-day mortality posthospital admission among blacks unique to the veterans affairs health care system? SO MEDICAL CARE LA English DT Article DE hospital mortality; racial disparities; veterans; hospitals ID ACUTE MYOCARDIAL-INFARCTION; ADMINISTRATIVE DATA; RACIAL-DIFFERENCES; COMORBIDITY MEASURES; HEART-FAILURE; UNITED-STATES; OUTCOMES; RACE; DISPARITIES; PERFORMANCE AB Background: Several studies have reported lower risk-adjusted mortality for blacks than whites within the Veterans Affairs (VA) health care system, particularly for those age 65 and older. This finding may be a result of the VA's integrated health care system, which reduces barriers to care through subsidized comprehensive health care services. However, no studies have directly compared racial differences in mortality within 30 days of hospitalization between the VA and non-VA facilities in the US health care system. Objective: To compare risk-adjusted 30-day mortality for black and white males after hospital admission to VA and non-VA hospitals, with separate comparisons for patients younger than age 65 and those age 65 and older. Research Design: Retrospective observational study using hospital claims data from the national VA system and all non-VA hospitals in Pennsylvania and California. Subjects: A total of 569,155 VA and 1,509,891 non-VA hospitalizations for a principal diagnosis of pneumonia, congestive heart failure, gastrointestinal bleeding, hip fracture, stroke, or acute myocardial infarction between 1996 and 2001. Measures: Mortality within 30 days of hospital admission. Results: Among those under age 65, blacks in VA and non-VA hospitals had similar odds ratios of 30-day mortality relative to whites for gastrointestinal bleeding, hip fracture, stroke, and acute myocardial infarction. Among those age 65 and older, blacks in both VA and non-VA hospitals had significantly reduced odds of 30-day mortality compared with whites for all conditions except pneumonia in the VA. The differences in mortality by race are remarkably similar in VA and non-VA settings. Conclusions: These findings suggest that factors associated with better short-term outcomes for blacks are not unique to the VA. C1 Univ Penn, Sch Med, Dept Gen Internal Med, Philadelphia, PA 19104 USA. VA Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. Univ Penn Wharton Sch, Dept Hlth Care Syst, San Francisco, CA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Hlth Policy & Management, Pittsburgh, PA USA. VA Boston Healthcare Syst, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA. RP Polsky, D (reprint author), Univ Penn, Sch Med, Dept Gen Internal Med, 1212 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM polsky@mail.med.upenn.edu NR 39 TC 14 Z9 14 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD NOV PY 2007 VL 45 IS 11 BP 1083 EP 1089 PG 7 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 227EI UT WOS:000250639600011 PM 18049349 ER PT J AU Yu, F Houston, TK Bay, MN Garner, DQ Berner, ES AF Yu, Feliciano Houston, Thomas K. Bay, Midge N. Garner, Duriel Q. Berner, Eta S. TI Patterns of use of handheld clinical decision support tools in the clinical setting SO MEDICAL DECISION MAKING LA English DT Article; Proceedings Paper CT 26th Annual Meeting of the Society-for-Medical-Decision-Making CY OCT 17-20, 2004 CL Atlanta, GA SP Soc Med Decis Making DE decision support systems; clinical; computers; handheld; decision making; computer assisted; internal medicine ID PERSONAL DIGITAL ASSISTANT; COMPUTER USE; RESIDENCY PROGRAMS; HEALTH-CARE; PHYSICIANS; ATTITUDES; EXPERIENCE; KNOWLEDGE; EDUCATION; SYSTEMS AB Objectives. To assess the patterns of use of handheld clinical decision support tools by internal medicine residents in clinical settings. Methods. Eighty-two internal medicine residents were given personal digital assistants (PDAs) containing a suite of clinical decision support (CDS) programs. A tracking program was used to prospectively track program use during the study period, and a follow-up survey regarding self-reported program use was administered after the study period. Patterns of program use from the tracking data were compared to the data from the self-report survey. Results. Sixty-eight residents were followed using the tracking data. Residents used an average of 1.81 CDS programs (SD: 1.57; range, 0-5) per month, Fortynine residents completed the self-report survey. Residents reported using an average of 3.15 (SD: 1.61) and 3.92 (SD: 1.40) CDS programs during a typical clinic session and inpatient day, respectively. In both inpatient and outpatient settings and for both methods of assessing program use, 2 programs (Epocrotes and MedCalc) were used more often than the other programs. No association was observed between age, gender, race, and PGY level with the use of handheld clinical decision support tools for either tracked or self-report data. The self-report data show higher estimates of CDS program use than the tracking data in the clinical setting. Conclusions. The data show that physicians prefer to use certain handheld CDS tools in clinical settings. Drug references and medical calculators have been consistently used more than clinical prediction rules and diagnostic systems. Self-report survey instruments may overestimate recorded use of CDS programs. C1 Univ Alabama, Div Emergency Med, Dept Pediat, Birmingham, AL 35233 USA. Univ Alabama, Ctr Outcomes & Effectiveness Res & Educ, Birmingham, AL USA. Univ Alabama, Dept Med, Birmingham, AL USA. Univ Alabama, Dept Hlth Serv Adm, Birmingham, AL USA. Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. Deep S Ctr Effectiveness Res, Birmingham, AL USA. Univ Alabama, Hlth Serv & Outcomes Res Training Program, Birmingham, AL USA. RP Yu, F (reprint author), Univ Alabama, Div Emergency Med, Dept Pediat, 1600 7th Ave S,Informat Technol,Suite 200-14, Birmingham, AL 35233 USA. EM fyu@peds.uab.edu RI Houston, Thomas/F-2469-2013; OI Berner, Eta/0000-0003-4319-2949 FU AHRQ HHS [R18 HS011820] NR 39 TC 5 Z9 5 U1 1 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0272-989X J9 MED DECIS MAKING JI Med. Decis. Mak. PD NOV-DEC PY 2007 VL 27 IS 6 BP 744 EP 753 DI 10.1177/0272989X07305321 PG 10 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA 236QN UT WOS:000251318600004 PM 17873262 ER PT J AU Razansky, D Ntziachristos, V AF Razansky, Daniel Ntziachristos, Vasilis TI Hybrid photoacoustic fluorescence molecular tomography using finite-element-based inversion SO MEDICAL PHYSICS LA English DT Article DE fluorescence molecular tomography; photoacoustic tomography; small animal imaging ID DIFFUSE OPTICAL TOMOGRAPHY; IN-VIVO; IMAGE-RECONSTRUCTION; APPROXIMATION; OXYGENATION; TISSUE; BRAIN AB Improvements in fluorescence reconstruction when utilizing a hybrid photoacoustic (PAT) fluorescence molecular tomography (FMT) method to image optically heterogeneous media are studied and showcased. Quantitative optical absorption maps are retrieved using a normalized backprojection algorithm for PAT reconstruction. Consecutively, the reconstructed absorption distribution is employed into computing a diffusion-equation-based forward model for FMT using a finite-element solution. The potential promise of the suggested method is experimentally verified on tissue-mimicking fluorescent phantoms, where improvements in the quality of FMT reconstructions are observed when imaging at the presence of a large absorber. (C) 2007 American Association of Physicists in Medicine. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. RP Razansky, D (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Mol Imaging Res, Charlestown, MA 02129 USA. EM daniel.razansky@gmail.com OI Razansky, Daniel/0000-0001-8676-0964 NR 36 TC 63 Z9 63 U1 1 U2 7 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD NOV PY 2007 VL 34 IS 11 BP 4293 EP 4301 DI 10.1118/1.2786866 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 234FK UT WOS:000251145900022 PM 18072494 ER PT J AU Gutchess, AH Kensinger, EA Yoon, C Schacter, DL AF Gutchess, Angela H. Kensinger, Elizabeth A. Yoon, Carolyn Schacter, Daniel L. TI Ageing and the self-reference effect in memory SO MEMORY LA English DT Article ID ADULT AGE-DIFFERENCES; OLDER-ADULTS; PROCESSING-SPEED; LIFE-SPAN; INFORMATION; ORGANIZATION; RECOGNITION; COGNITION; YOUNGER; RATINGS AB The present study investigates potential age differences in the self-reference effect. Young and older adults incidentally encoded adjectives by deciding whether the adjective described them, described another person (Experiments 1 & 2), was a trait they found desirable (Experiment 3), or was presented in upper case. Like young adults, older adults exhibited superior recognition for self-referenced items relative to the items encoded with the alternate orienting tasks, but self-referencing did not restore their memory to the level of young adults. Furthermore, the self-reference effect was more limited for older adults. Amount of cognitive resource influenced how much older adults benefit from self-referencing, and older adults appeared to extend the strategy less flexibly than young adults. Self-referencing improves older adults' memory, but its benefits are circumscribed despite the social and personally relevant nature of the task. C1 [Gutchess, Angela H.; Schacter, Daniel L.] Harvard Univ, Cambridge, MA 02138 USA. [Gutchess, Angela H.; Kensinger, Elizabeth A.; Schacter, Daniel L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kensinger, Elizabeth A.] Boston Coll, Chestnut Hill, MA 02167 USA. [Yoon, Carolyn] Univ Michigan, Ann Arbor, MI 48109 USA. RP Gutchess, AH (reprint author), Brandeis Univ, Dept Psychol, MS 062,POB 549110, Waltham, MA 02454 USA. EM gutchess@brandeis.edu OI Schacter, Daniel/0000-0002-2460-6061 FU NIA NIH HHS [R01 AG008441, F32 AG026920]; NIMH NIH HHS [MH 070199] NR 50 TC 56 Z9 56 U1 0 U2 10 PU PSYCHOLOGY PRESS PI HOVE PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND SN 0965-8211 J9 MEMORY JI Memory PD NOV PY 2007 VL 15 IS 8 BP 822 EP 837 DI 10.1080/09658210701701394 PG 16 WC Psychology, Experimental SC Psychology GA 244RF UT WOS:000251882300003 PM 18033620 ER PT J AU Shifren, JL Desindes, S McIlwain, M Doros, G Mazer, NA AF Shifren, Jan L. Desindes, Sophie McIlwain, Marilyn Doros, Gheorghe Mazer, Norman A. TI A randomized, open-label, crossover study comparing the effects of oral versus transdermal estrogen therapy on serum androgens, thyroid hormones, and adrenal hormones in naturally menopausal women SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Article; Proceedings Paper CT 86th Annual Meeting of the Endocrine-Society CY JUN 12-15, 2004 CL New Orleans, LA SP Endocrine Soc DE androgen; estrogen; menopause; thyroid; adrenal; transdermal ID PLACEBO-CONTROLLED TRIAL; SEXUAL DESIRE DISORDER; POSTMENOPAUSAL WOMEN; REPLACEMENT THERAPY; BINDING GLOBULIN; FREE TESTOSTERONE; AROMATASE INHIBITION; CLINICAL-TRIALS; ESTRADIOL; CORTISOL AB Objective: To compare the changes induced by oral versus transdermal estrogen therapy on the total and free serum concentrations of testosterone (T), thyroxine (T-4), and cortisol (C) and the concentrations of their serum binding globulins sex hormone-binding globulin, thyroxine-binding globulin, and cortisol-binding globulin in naturally menopausal women. Design: Randomized, open-label, crossover. Interventions included a 6-week withdrawal from previous hormone therapy (baseline), followed in randomized order by 12 weeks of oral conjugated equine estrogens (CEE) (0.625 mg/d) and 12 weeks of transdermal estradiol (TD E-2) (0.05 mg/d), with oral micronized progesterone (100 mg/d) given continuously during both transdermal estrogen therapy regimens. Results: Twenty-seven women were enrolled in the study, and 25 completed both treatment periods. The mean (SD) percentage changes from baseline of sex hormone-binding globulin, total T, and free T with oral CEE were +132.1% (74.5%), +16.4% (43.8%), and -32.7% (25.9%), respectively, versus +12.0% (25.1%), +1.2% (43.7%), and +1.0% (45.0%) with TD E-2. The mean (SD) percentage changes of thyroxine-binding globulin, total T-4, and free T4 with oral CEE were +39.9% (20.1%), +28.4% (29.2%), and - 10.4% (22.3%), respectively, versus +0.4% (11.1%), -0.7% (16.5%), and +0.2% (26.6%) with TD E-2. The mean (SD) percentage changes of cortisol-binding globulin, total C, and free C with oral CEE were +18.0% (19.5%), +29.2% (46.3%), and +50.4% (126.5%), respectively, versus -2.2% (11.3%), -6.7% (30.8%), and +1.8% (77.1%) with TD E-2-Concentrations of all hormones and binding globulins were significantly different (P <= 0.003) during administration of oral versus transdermal estrogen therapy, except for free T-4 and free C. Conclusions: Compared with oral CEE, TD E-2 exerts minimal effects on the total and free concentrations of T, T-4, and C and their binding proteins. C1 [Shifren, Jan L.] Massachusetts Gen Hosp, Vincents Obstet & Gynecol Serv, Boston, MA 02114 USA. [Shifren, Jan L.] Harvard Med Sch, Boston, MA USA. [Desindes, Sophie] Univ Sherbrooke, Sherbrooke, PQ J1K 2R1, Canada. [McIlwain, Marilyn] Watson Labs Inc, Morristown, NJ USA. [Doros, Gheorghe] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. [Mazer, Norman A.] Boston Univ, Sch Med, Sect Endocrinol Diabet & Nutr, Boston, MA 02215 USA. RP Shifren, JL (reprint author), Massachusetts Gen Hosp, Vincents Obstet & Gynecol Serv, Boston, MA 02114 USA. NR 52 TC 37 Z9 38 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD NOV-DEC PY 2007 VL 14 IS 6 BP 985 EP 994 DI 10.1097/gme.0b013e31803867a PG 10 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 231KG UT WOS:000250945000008 PM 17507833 ER PT J AU Hall, SA Link, CL Schiff, I McKinlay, JB AF Hall, Susan A. Link, Carol L. Schiff, Isaac McKinlay, John B. TI The relationship between menopausal status and urinary symptoms: Results from the BACH study SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Meeting Abstract CT 18th Annual Meeting of the North-American-Menopause-Society CY OCT 03-06, 2007 CL Dallas, TX SP N Amer Menopause Soc C1 [Hall, Susan A.; Link, Carol L.; McKinlay, John B.] New England Res Inst, Watertown, MA USA. [Schiff, Isaac] Massachusetts Gen Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD NOV-DEC PY 2007 VL 14 IS 6 BP 1082 EP 1082 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 231KG UT WOS:000250945000059 ER PT J AU Avis, NE Legault, C Cocytaux, RR Pian-Smith, M Shiften, JL Valasgatkis, P AF Avis, Nancy E. Legault, Claudine Cocytaux, Remy R. Pian-Smith, May Shiften, Jan L. Valasgatkis, Peter TI Acupuncture treatment for hot flashes SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Meeting Abstract CT 18th Annual Meeting of the North-American-Menopause-Society CY OCT 03-06, 2007 CL Dallas, TX SP N Amer Menopause Soc C1 [Avis, Nancy E.; Legault, Claudine] Wake Forest Univ, Sch Med, Winston Salem, NC USA. [Cocytaux, Remy R.] Univ N Carolina, Chapel Hill, NC USA. [Pian-Smith, May; Shiften, Jan L.] Massachusetts Gen Hosp, Boston, MA USA. [Valasgatkis, Peter] New England Sch Acupunct, Watertown, 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 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD NOV-DEC PY 2007 VL 14 IS 6 BP 1083 EP 1083 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 231KG UT WOS:000250945000063 ER PT J AU Thurston, RC Chang, Y Joffe, H Avis, N Bromberger, J Hess, R Crandall, C Green, R Matthews, K AF Thurston, Rebecca C. Chang, Yuefang Joffe, Hadine Avis, Nancy Bromberger, Joyce Hess, Rachel Crandall, Carolyn Green, Robin Matthews, Karen TI Beyond frequency: Who is most bothered by vasomotor symptoms? SO MENOPAUSE-THE JOURNAL OF THE NORTH AMERICAN MENOPAUSE SOCIETY LA English DT Meeting Abstract CT 18th Annual Meeting of the North-American-Menopause-Society CY OCT 03-06, 2007 CL Dallas, TX SP N Amer Menopause Soc C1 [Thurston, Rebecca C.; Chang, Yuefang; Bromberger, Joyce; Hess, Rachel; Matthews, Karen] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. [Joffe, Hadine] Massachusetts Gen Hosp, Boston, MA USA. [Avis, Nancy] Wake Forest Univ, Winston Salem, NC 27109 USA. [Crandall, Carolyn] Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. [Green, Robin] Albert Einstein Coll Med, New York, NY 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 1072-3714 J9 MENOPAUSE JI Menopause-J. N. Am. Menopause Soc. PD NOV-DEC PY 2007 VL 14 IS 6 BP 1106 EP 1106 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 231KG UT WOS:000250945000153 ER PT J AU Weinrauch, LA Burger, AJ Aepfelbacher, F Lee, AT Gleason, RE D'Elia, JA AF Weinrauch, Larry A. Burger, Andrew J. Aepfelbacher, Franz Lee, Annette T. Gleason, Ray E. D'Elia, John A. TI A pilot study to test the effect of pulsatile insulin infusion on cardiovascular mechanisms that might contribute to attenuation of renal compromise in type 1 diabetes mellitus patients with proteinuria SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article; Proceedings Paper CT 40th Scientific Meeting of the American-Society-of-Nephrology CY NOV, 2007 CL San Diego, CA SP Amer Soc Nephrol ID IMPROVED GLYCEMIC CONTROL; GROWTH-FACTOR; INTERMITTENT; NEPHROPATHY; DYSFUNCTION; METABOLISM; GLYCATION; OXIDATION; THERAPY; GLUCOSE AB We hypothesized that correction of insulin deficiency by pulsatile intravenous insulin infusion in type I diabetes mellims patients with nephropathy preserves renal function by mechanisms involving cardiac autonomic function, cardiac mass, or efficiency, or by hemostatic mechanisms. The control group (8 patients) received subcutaneous insulin (34 injections per day). The intravenous infusion group (10 patients) received three I -hour courses of pulsed intravenous insulin infusion on a single day per week in addition to subcutaneous insulin. Laboratory measurements included 2-dimensional Doppler echocardiography, 24-hour ambulatory monitoring with heart rate variation analysis, platelet aggregation and adhesion, plasma fibrinogen, factor VII, von Willebrand factor, fibrinolytic activity, plasminogen activator inhibitor, and viscosity measured at baseline and 12 months. Blood pressure control was maintained preferentially with angiotensin-converting enzyme inhibitors. Ratio of carbon dioxide production to oxygen utilization was measured with each infusion and showed rapid increase from 0.8 to 0.9 (P =.005) at weekly treatments through 12 months. We observed an annualized decrease in creatinine clearance of 9.6 mL/min for controls vs 3.0 mL/min for infusion patients. Annualized fall in blood hemoglobin was 1.9 vs 0.8 g/dL, respectively (P =.013). There were no differences between the control and infusion group with respect to glycohemoglobin, advanced glycated end products, cholesterol, or triglycerides. No differences between the study groups for hernodynamic or hemostatic factors were evident. Blood pressures were not significantly different at baseline or 12 months. We conclude that although preservation of renal function with attenuation of loss of blood hemoglobin during 12 months of intravenous insulin infusion was associated with improvement in the efficiency of fuel oxidation as measured by respiratory quotient, this occurred without differences in metabolic/hemostatic factors, cardiac autonomic function, cardiac wall, or chamber size. Our hypothesis that preservation of renal function in type I diabetes mellitus patients with proteinuria by weekly pulsed insulin infusion involves mechanisms from the autonomic nervous system, cardiac size, and function, or elements of hernostasis was not confirmed. (C) 2007 Elsevier Inc. All rights reserved. C1 Joslin Diabet Ctr, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Mt Auburn Hosp, Cambridge, MA USA. Harvard Univ, Sch Med, Boston, MA USA. N Shore Univ Hosp, Manhasset, NY USA. RP Weinrauch, LA (reprint author), 521 Mt Auburn St,Suite 204, Watertown, MA 02472 USA. EM lweinrauch@hms.harvard.edu OI D'Elia, John/0000-0001-9482-581X; Weinrauch, Larry/0000-0003-1357-9528 NR 22 TC 5 Z9 5 U1 0 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 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD NOV PY 2007 VL 56 IS 11 BP 1453 EP 1457 DI 10.1016/j.metabol.2007.05.016 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 224ZW UT WOS:000250487900001 PM 17950093 ER PT J AU Djapa, LY Basco, LK Zelikson, R Rosowsky, A Djaman, JA Yonkeu, JN Bolotin-Fukuhara, M Mazabraud, A AF Djapa, Liselotte Yimga Basco, Leonardo K. Zelikson, Ruth Rosowsky, Andre Djaman, Joseph Allico Yonkeu, Jeanne Ngogang Bolotin-Fukuhara, Monique Mazabraud, Andre TI Antifolate screening using yeast expressing Plasmodium vivax dihydrofolate reductase and in vitro drug susceptibility assay for Plasmodium falciparum SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE antifolate drugs; Plasmodium vivax; Plasmodium falciparum in vitro culture; malaria; yeast; drug resistance ID THYMIDYLATE SYNTHASE GENE; RESISTANCE; PYRIMETHAMINE; SEQUENCE; MALARIA AB The presence of homologous point mutations in the dhfr gene in Plasmodium vivax and Plasmodium falciparum is associated with resistance to antifolate drugs. The spread of antifolate resistance encouraged research for novel antifolate drugs active against both wild-type and dhfr-mutant strains of malaria parasites. Because P. vivax cannot be easily maintained in culture, we transformed a Saccharomyces cerevisiae DHFR-deleted mutant to express wild-type P. vivax dhfr gene and its mutant forms. Twenty-five dicyclic and tricyclic 2,4-diaminopyrimidine derivatives were screened. Six quinazoline compounds showed selective inhibition of yeast transformants expressing R vivax dhfr genes. The 50% inhibitory concentration (IC50) of these six compounds was determined against field isolates of P falciparum. Our results suggest that a close relationship between the yeast assay based on expression of R vivax dhfr genes and the in vitro test using P falciparum parasites in culture is a promising initial step for drug screening. (C) 2007 Elsevier B.V. All rights reserved. C1 Univ Paris 11, CNRS, UMR 8080, F-91405 Orsay, France. CNRS, UMR 8621, F-91405 Orsay, France. IRD, OCEAC, Yaounde, Cameroon. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Cocody, Biochim Lab, Inst Pasteur Cote Invoire, Abidjan, Cote Ivoire. Univ Cocody, Lab Pharmacodynamie Biochim, Abidjan, Cote Ivoire. Univ Yaounde, Fac Med & Biomed Sci, Yaounde, Cameroon. RP Mazabraud, A (reprint author), Univ Paris 11, CNRS, UMR 8080, Bat 445, F-91405 Orsay, France. EM andre.mazabraud@u-psud.fr NR 12 TC 8 Z9 8 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-6851 J9 MOL BIOCHEM PARASIT JI Mol. Biochem. Parasitol. PD NOV PY 2007 VL 156 IS 1 BP 89 EP 92 DI 10.1016/j.molbiopara.2007.07.009 PG 4 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA 223UZ UT WOS:000250399200011 PM 17727978 ER PT J AU Stephenson, LM Sammut, B Graham, DB Chan-Wang, J Brim, KL Huett, AS Miletic, AV Kloeppel, T Landry, A Xavier, R Swat, W AF Stephenson, Linda M. Sammut, Benedicte Graham, Daniel B. Chan-Wang, Joaquim Brim, Karry L. Huett, Alan S. Miletic, Ana V. Kloeppel, Tracie Landry, Aimee Xavier, Ramnik Swat, Woiciech TI DLGH1 is a negative regulator of T-lympliocyte proliferation SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID EPITHELIAL-CELL POLARITY; LARGE TUMOR-SUPPRESSOR; LYMPHOCYTE-ACTIVATION; HUMAN HOMOLOG; PDZ DOMAINS; PROTEINS; KINASE; MEMBRANE; RECEPTOR; COMPLEX AB Discs large homolog 1 (DLGH1), a founding member of the membrane-associated guanylate kinase family of proteins containing PostSynaptic Density-95/Discs large/Zona Occludens-1 domains, is an ortholog of the Drosophila tumor suppressor gene Discs large. In the mammalian embryo, DLGH1 is essential for normal urogenital morphogenesis and the development of skeletal and epithelial structures. Recent reports also indicate that DLGH1 may be a critical mediator of signals triggered by the antigen receptor complex in T lymphocytes by functioning as a scaffold coordinating the activities of T-cell receptor (TCR) signaling proteins at the immune synapse. However, it remains unclear if DLGH1 functions to enhance or attenuate signals emanating from the TCR. Here, we used Digh1 gene-targeted mice to determine the requirement for DLGH1 in T-cell development and activation. Strikingly, while all major subsets of T cells appear to undergo normal thymic development in the absence of DLGH1, peripheral lymph node Dlgh1(-/-) T cells show a hyperproliferative response to TCR-induced stimulation. These data indicate that, consistent with the known function of Discs large proteins as tumor suppressors and attenuators of cell division, in T lymphocytes, DLGH1 functions as a negative regulator of TCR-induced proliferative responses. C1 Washington Univ, Dept Pathol & Immunol, Sch Med, St Louis, MO 63110 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Computat & Intergrat Biol, Boston, MA 02115 USA. RP Xavier, R (reprint author), Washington Univ, Dept Pathol & Immunol, Sch Med, 660 S Euclid Ave, St Louis, MO 63110 USA. EM xavier@molbio.mgh.harvard.edu; swat@wustl.edu FU NCI NIH HHS [T32 CA009547]; NIAID NIH HHS [R01-AI061077, 5-T32-AI07163-27, R01 AI061077, T32 AI007163]; NIAMS NIH HHS [P30-AR048335, P30 AR048335]; NIDDK NIH HHS [P30 DK040561-12, P30 DK040561] NR 33 TC 25 Z9 26 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD NOV PY 2007 VL 27 IS 21 BP 7574 EP 7581 DI 10.1128/MCB.00439-07 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 223LK UT WOS:000250371600019 PM 17724087 ER PT J AU Pathak, N Obara, T Mangos, S Liu, Y Drummond, IA AF Pathak, Narendra Obara, Tomoko Mangos, Steve Liu, Yan Drummond, Iain A. TI The zebrafish fleer gene encodes an essential regulator of cilia tubulin polyglutamylation SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID LEFT-RIGHT ASYMMETRY; INTRAFLAGELLAR TRANSPORT; ALPHA-TUBULIN; C-TERMINUS; CAENORHABDITIS-ELEGANS; PROTEOMIC ANALYSIS; KUPFFERS VESICLE; BETA-TUBULIN; FLAGELLAR; KINESIN AB Cilia and basal bodies are essential organelles for a broad spectrum of functions, including the development of left-right asymmetry, kidney function, cerebrospinal fluid transport, generation of photoreceptor outer segments, and hedgehog signaling. Zebrafish fleer (flr) mutants exhibit kidney cysts, randomized left-right asymmetry, hydrocephalus, and rod outer segment defects, suggesting a pleiotropic defect in ciliogenesis. Positional cloning flr identified a tetratricopeptide repeat protein homologous to the Caenorhabditis elegans protein DYF1 that was highly expressed in ciliated cells. flr pronephric cilia were shortened and showed a reduced beat amplitude, and olfactory cilia were absent in mutants. flr cilia exhibited ultrastructural defects in microtubule 13-tubules, similar to axonemes that lack tubulin posttranslational modifications (polyglutamylation or polyglycylation). flr cilia showed a dramatic reduction in cilia polyglutamylated tubulin, indicating that flr encodes a novel modulator of tubulin polyglutamylation. We also found that the C. elegans flr homologue, dyf-1, is also required for tubulin polyglutamylation in sensory neuron cilia. Knockdown of zebrafish Tt116, a tubulin polyglutamylase, specifically eliminated tubulin polyglutamylation and cilia formation in olfactory placodes, similar to flr mutants. These results are the first in vivo evidence that tubulin polyglutamylation is required for vertebrate cilia motility and structure, and, when compromised, results in failed ciliogenesis. C1 Massachusetts Gen Hosp, Div Nephrol, Charlestown, MA 02129 USA. RP Drummond, IA (reprint author), Massachusetts Gen Hosp, Div Nephrol, Charlestown, MA 02129 USA. EM idrununon@receptor.mgh.harvard.edu FU NIDDK NIH HHS [DK-53093, DK-54711, P01 DK054711, R01 DK053093, R01 DK078209, R21 DK069604, T32 DK007540, T32-DK007540-20] NR 47 TC 106 Z9 111 U1 0 U2 12 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD NOV PY 2007 VL 18 IS 11 BP 4353 EP 4364 DI 10.1091/mbc.E07-06-0537 PG 12 WC Cell Biology SC Cell Biology GA 228OT UT WOS:000250740000013 PM 17761526 ER PT J AU Kovalenko, OV Yang, XWH Hemler, ME AF Kovalenko, Oleg V. Yang, Xiuwei H. Hemler, Martin E. TI A novel cysteine cross-linking method reveals a direct association between claudin-1 and tetraspanin CD9 SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Article ID TIGHT JUNCTIONS; GROWTH-FACTOR; TRANSMEMBRANE-4 SUPERFAMILY; ENRICHED MICRODOMAINS; CD9-DEFICIENT MICE; EPITHELIAL-CELLS; PLASMA-MEMBRANE; CD81 FUNCTION; COLON-CANCER; MAJOR CD9 AB Tetraspanins serve as molecular organizers of multiprotein microdomains in cell membranes. Hence to understand functions of tetraspanin proteins, it is critical to identify laterally interacting partner proteins. Here we used a novel technical approach involving exposure and cross-linking of membrane-proximal cysteines coupled with LC-MS/MS protein identification. In this manner we identified nine potential tetraspanin CD9 partners, including claudin-1. Chemical cross-linking yielded a CD9-claudin-1 heterodimer, thus confirming direct association and adding claudin-1 to the short list of proteins that can directly associate with CD9. Interaction of CD9 (and other tetraspanins) with claudin-1 was supported by subcellular colocalization and was confirmed in multiple cell lines, although other claudins (claudin- 2, -3, -4, -5, and -7) associated to a much lesser extent. Moreover claudin- 1 was distributed very similarly to CD9 in sucrose gradients and, like CD9, was released from A431 and A549 cells upon cholesterol depletion. These biochemical features of claudin-1 are characteristic of tetraspanin microdomain proteins. Although claudins are major structural components of intercellular tight junctions, CD9-claudin-1 complexes did not reside in tight junctions, and depletion of key tetraspanins (CD9 and CD151) by small interfering RNA had no effect on paracellular permeability. However, tetraspanin depletion did cause a marked decrease in the stability of newly synthesized claudin-1. In conclusion, these results (a) validate a technical approach that appears to be particularly well suited for identifying protein partners directly associated with tetraspanins or with other proteins that contain membrane-proximal cysteines and (b) provide insight into how non-junctional claudins may be regulated in the context of tetraspanin-enriched microdomains. C1 [Kovalenko, Oleg V.; Yang, Xiuwei H.; Hemler, Martin E.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Kovalenko, Oleg V.; Yang, Xiuwei H.; Hemler, Martin E.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Hemler, ME (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, D 1430,44 Binney St, Boston, MA 02115 USA. FU NIGMS NIH HHS [GM38903] NR 78 TC 59 Z9 60 U1 0 U2 8 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD NOV PY 2007 VL 6 IS 11 BP 1855 EP 1867 DI 10.1074/mcp.M700183-MCP200 PG 13 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 239XZ UT WOS:000251552900003 PM 17644758 ER PT J AU Duan, Z Bradner, J Greenberg, E Mazitschek, R Foster, R Mahoney, J Seiden, MV AF Duan, Zhenfeng Bradner, James Greenberg, Edward Mazitschek, Ralph Foster, Rosemary Mahoney, Jennifer Seiden, Michael V. TI 8-benzyl-4-oxo-8-azabicyclo[3.2.1]oct-2-ene-6,7-dicarboxylic acid (SD-1008), a novel janus kinase 2 inhibitor, increases chemotherapy sensitivity in human ovarian cancer cells SO MOLECULAR PHARMACOLOGY LA English DT Article ID ACTIVATED SIGNAL TRANSDUCER; ACUTE MYELOID-LEUKEMIA; CONSTITUTIVE ACTIVATION; PACLITAXEL RESISTANCE; STAT3 ACTIVATION; TYROSINE KINASE; CONFERS RESISTANCE; MOLECULAR TARGETS; MULTIPLE-MYELOMA; CARCINOMA CELLS AB Interleukin 6 and the signal transducer and activator of transcription (STAT) 3 proteins have important roles in cancer cell survival and proliferation. Recent studies demonstrate that abnormal STAT3 activation promotes tumor growth and supports survival of many human cancers, and thus, this protein or the pathway responsible for its activation is a potential target for the new anticancer therapy. STAT3 is a DNA binding transcription factor, and therefore, its function depends on nuclear translocation. To discover inhibitors of the STAT3 pathway, we designed a cell-based screening assay capable of identifying small molecules that inhibit nuclear translocation. Among the 2000-compound National Cancer Institute Diversity set, we identified 8-benzyl-4-oxo-8-azabicyclo[3.2.1]oct-2-ene-6,7-dicarboxylic acid (SD-1008) as a micromolar inhibitor of interleukin6 or oncostatin-induced STAT3 nuclear translocation. In addition, SD-1008 inhibits tyrosyl phosphorylation of STAT3, Janus kinase 2 (JAK2), and Src. SD-1008 also reduces STAT3-dependent luciferase activity. Biochemical studies with recombinant JAK2 proteins demonstrate that high concentrations of SD-1008 directly inhibit JAK2 kinase autophosphorylation. Exposure of various cell lines to SD-1008 decreases levels of the STAT3-dependent proteins, Bcl-X-L and survivin, inducing apoptosis. SD-1008 also enhances apoptosis induced by paclitaxel in ovarian cancer cells. These results demonstrate that SD-1008 directly blocks the JAK-STAT3 signaling pathway in human cancer cells that express constitutively active Stat and add to the growing literature that identifies this pathway as a viable target for drug development. Finally, SD-1008 may be a suitable prototype for further chemical modification and exploration as a therapeutic agent. C1 [Duan, Zhenfeng; Mahoney, Jennifer; Seiden, Michael V.] Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02114 USA. [Greenberg, Edward; Mazitschek, Ralph] Broad Inst Harvard, Chem Biol Program, Cambridge, MA USA. [Greenberg, Edward; Mazitschek, Ralph] MIT, Cambridge, MA 02139 USA. RP Duan, Z (reprint author), Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02114 USA. RI Mazitschek, Ralph/E-3741-2013 OI Mazitschek, Ralph/0000-0002-1105-689X FU NCI NIH HHS [1K24-CA109416-01A1, 1P50-CA105009] NR 41 TC 29 Z9 30 U1 0 U2 2 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD NOV PY 2007 VL 72 IS 5 BP 1137 EP 1145 DI 10.1124/mol.107.038117 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 223PR UT WOS:000250385300007 PM 17675586 ER PT J AU Junt, T Moseman, EA Iannacone, M Massberg, S Lang, PA Boes, M Fink, K Henrickson, SE Shayakhmetov, DM Di Paolo, NC Van Rooijen, N Mempel, TR Whelan, SP von Andrian, UH AF Junt, Tobias Moseman, E. Ashley Iannacone, Matteo Massberg, Steffen Lang, Philipp A. Boes, Marianne Fink, Katja Henrickson, Sarah E. Shayakhmetov, Dmitry M. Di Paolo, Nelson C. Van Rooijen, Nico Mempel, Thorsten R. Whelan, Sean P. von Andrian, Ulrich H. TI Subcapsular sinus macrophages in lymph nodes clear lymph-borne viruses and present them to antiviral B cells SO NATURE LA English DT Article ID VESICULAR STOMATITIS-VIRUS; DENDRITIC CELLS; IMMUNE-RESPONSES; IN-VIVO; MICE; COMPLEMENT; ORGANS; LYMPHOCYTES; ANTIBODIES; RECEPTORS AB Lymph nodes prevent the systemic dissemination of pathogens such as viruses that infect peripheral tissues after penetrating the body's surface barriers. They are also the staging ground of adaptive immune responses to pathogen-derived antigens(1,2). It is unclear how virus particles are cleared from afferent lymph and presented to cognate B cells to induce antibody responses. Here we identify a population of CD11b(+)CD169(+)MHCII(+) macrophages on the floor of the subcapsular sinus (SCS) and in the medulla of lymph nodes that capture viral particles within minutes after subcutaneous injection. Macrophages in the SCS translocated surface-bound viral particles across the SCS floor and presented them to migrating B cells in the underlying follicles. Selective depletion of these macrophages compromised local viral retention, exacerbated viraemia of the host, and impaired local B-cell activation. These findings indicate that CD169(+) macrophages have a dual physiological function. They act as innate 'flypaper' by preventing the systemic spread of lymph-borne pathogens and as critical gatekeepers at the lymph-tissue interface that facilitate the recognition of particulate antigens by B cells and initiate humoral immune responses. C1 Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Dermatol, Boston, MA 02115 USA. Ist Sci San Raffaele, Immunopathogenesis Liver Infect Unit, I-20132 Milan, Italy. Univ Zurich Hosp, Inst Expt Immunol, CH-8091 Zurich, Switzerland. Novartis Inst Trop Dis, Singapore 138670, Singapore. Univ Washington, Dept Med, Div Med Genet, Seattle, WA 98195 USA. Vrije Univ Amsterdam, VUMC, Fac Med, Dept Mol Cell Biol, NL-1081 BT Amsterdam, Netherlands. Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, Boston, MA 02115 USA. RP von Andrian, UH (reprint author), Harvard Univ, Sch Med, Immune Dis Inst, 77 Ave Louis Pasteur, Boston, MA 02115 USA. EM uva@hms.harvard.edu RI Iannacone, Matteo/B-3342-2008; von Andrian, Ulrich/A-5775-2008; OI Iannacone, Matteo/0000-0002-9370-2671 FU NIAID NIH HHS [R01 AI059371, R01 AI059371-03]; NIGMS NIH HHS [T32 GM007753] NR 29 TC 362 Z9 365 U1 7 U2 27 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 1 PY 2007 VL 450 IS 7166 BP 110 EP + DI 10.1038/nature06287 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 226JR UT WOS:000250585800047 PM 17934446 ER PT J AU Ishikawa, F Yoshida, S Saito, Y Hijikata, A Kitamura, H Tanaka, S Nakamura, R Tanaka, T Tomiyama, H Saito, N Fukata, M Miyamoto, T Lyons, B Ohshima, K Uchida, N Taniguchi, S Ohara, O Akashi, K Harada, M Shultz, LD AF Ishikawa, Fumihiko Yoshida, Shuro Saito, Yoriko Hijikata, Atsushi Kitamura, Hiroshi Tanaka, Satoshi Nakamura, Ryu Tanaka, Toru Tomiyama, Hiroko Saito, Noriyuki Fukata, Mitsuhiro Miyamoto, Toshihiro Lyons, Bonnie Ohshima, Koichi Uchida, Naoyuki Taniguchi, Shuichi Ohara, Osamu Akashi, Koichi Harada, Mine Shultz, Leonard D. TI Chemotherapy-resistant human AML stem cells home to and engraft within the bone-marrow endosteal region SO NATURE BIOTECHNOLOGY LA English DT Article ID ACUTE MYELOID-LEUKEMIA; SCID MICE; PROGENITOR CELLS; GENE-EXPRESSION; NOD/SCID MICE; R-PACKAGE; NICHE; CD44; HEMATOPOIESIS; HIERARCHY AB Acute myelogenous leukemia (AML) is the most common adult leukemia, characterized by the clonal expansion of immature myeloblasts initiating from rare leukemic stem (LS) cells(1-3). To understand the functional properties of human LS cells, we developed a primary human AML xenotransplantation model using newborn nonobese diabetic/severe combined immunodeficient/interleukin (NOD/SCID/IL)2r gamma(null) mice carrying a complete null mutation of the cytokine gamma c upon the SCID background(4). Using this model, we demonstrated that LS cells exclusively recapitulate AML and retain self-renewal capacity in vivo. They home to and engraft within the osteoblast-rich area of the bone marrow, where AML cells are protected from chemotherapy-induced apoptosis. Quiescence of human LS cells may be a mechanism underlying resistance to cell cycle-dependent cytotoxic therapy. Global transcriptional profiling identified LS cell-specific transcripts that are stable through serial transplantation. These results indicate the potential utility of this AML xenograft model in the development of novel therapeutic strategies targeted at LS cells. C1 RIKEN, Res Ctr All & Immunol, Res Unit Human Dis Models, Yokohama, Kanagawa 2300045, Japan. RIKEN, Res Ctr All & Immunol, Lab Immunogennom, Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan. Kyushu Univ, Grad Sch, Dept Med & Biosyst Sci, Fukuoka 8128582, Japan. Kyushu Univ Hosp, Ctr Cellular & Mol, Higashi Ku, Fukuoka 8128582, Japan. Harvard Univ, Massachusetts Gen Hosp, Harvard Med Sch, Dept Pathol, Boston, MA 02114 USA. Nippon Becton Dickinson Co, Minato Ku, Tokyo 1070052, Japan. Carl Zeisss, Shinjuku Ku, Tokyo, Japan. Jackson Lab, Bar Harbor, ME 04609 USA. Kurume Univ, Sch Med, Dept Pathol 1, Kurume, Fukuoka 8300003, Japan. Toranomon Gen Hosp, Dept Hematol, Minato Ku, Tokyo 14058470, Japan. Kazusa DNA Res Inst, Dept Human Genome Technol, Kisarazu 2900818, Japan. Harvard Univ, Harvard Med Sch, Dana Farber Canc Inst, Dept Canc Immunol,AIDS, Boston, MA 02115 USA. RP Ishikawa, F (reprint author), RIKEN, Res Ctr All & Immunol, Res Unit Human Dis Models, Yokohama, Kanagawa 2300045, Japan. EM f_ishika@rcai.riken.jp RI Ohara, Osamu/A-9119-2012; 石川, 文彦/L-4488-2014; Ohara, Osamu/G-5448-2015 OI Ohara, Osamu/0000-0002-3328-9571 NR 30 TC 410 Z9 425 U1 3 U2 32 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD NOV PY 2007 VL 25 IS 11 BP 1315 EP 1321 DI 10.1038/nbt1350 PG 7 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 233JF UT WOS:000251086500033 PM 17952057 ER PT J AU Love, KR Catic, A Schlieker, C Ploegh, HL AF Love, Kerry Routenberg Catic, Andre Schlieker, Christian Ploegh, Hidde L. TI Mechanisms, biology and inhibitors of deubiquitinating enzymes SO NATURE CHEMICAL BIOLOGY LA English DT Article ID NF-KAPPA-B; UBIQUITIN-SPECIFIC PROTEASE; CARBOXYL-TERMINAL HYDROLASE; LARGE TEGUMENT PROTEIN; FUNCTIONAL PROTEOMICS; ISOPEPTIDASE ACTIVITY; PARKINSONS-DISEASE; CYSTEINE PROTEASES; ATAXIA MICE; SUBSTRATE AB The addition of ubiquitin (Ub) and ubiquitin-like (Ubl) modifiers to proteins serves to modulate function and is a key step in protein degradation, epigenetic modification and intracellular localization. Deubiquitinating enzymes and Ubl-specific proteases, the proteins responsible for the removal of Ub and Ubls, act as an additional level of control over the ubiquitin-proteasome system. Their conservation and widespread occurrence in eukaryotes, prokaryotes and viruses shows that these proteases constitute an essential class of enzymes. Here, we discuss how chemical tools, including activity-based probes and suicide inhibitors, have enabled (i) discovery of deubiquitinating enzymes, (ii) their functional profiling, crystallographic characterization and mechanistic classification and (iii) development of molecules for therapeutic purposes. C1 Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. Massachusetts Gen Hosp, Harvard Stem Cell Inst, Boston, MA 02114 USA. RP Love, KR (reprint author), Whitehead Inst Biomed Res, 9 Cambridge Ctr, Cambridge, MA 02142 USA. EM ploegh@wi.mit.edu FU NIAID NIH HHS [F32 AI63854] NR 94 TC 131 Z9 131 U1 5 U2 29 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1552-4450 J9 NAT CHEM BIOL JI Nat. Chem. Biol. PD NOV PY 2007 VL 3 IS 11 BP 697 EP 705 DI 10.1038/nchembio1107-695 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 222QH UT WOS:000250311500009 PM 17948018 ER PT J AU Leder, BZ AF Leder, Benjamin Z. TI Is parathyroid hormone (1-84) a safe and effective treatment for postmenopausal osteoporosis? SO NATURE CLINICAL PRACTICE ENDOCRINOLOGY & METABOLISM LA English DT Editorial Material DE BMD; bone formation; fracture; osteoporosis; parathyroid hormone (1-84) ID BONE-MINERAL DENSITY; WOMEN; RATS C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. RP Leder, BZ (reprint author), Massachusetts Gen Hosp, Endocrine Unit, 50 Blossom St,THR 1015, Boston, MA 02114 USA. EM bzleder@partners.org NR 6 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1745-8366 J9 NAT CLIN PRACT ENDOC JI Nat. Clin. Pract. Endocrinol. Metab. PD NOV PY 2007 VL 3 IS 11 BP 746 EP 747 DI 10.1038/ncpendmet0626 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 221NF UT WOS:000250233900008 PM 17768406 ER PT J AU Henson, JW Avitzur, O AF Henson, John W. Avitzur, Orly TI The online neurologist SO NATURE CLINICAL PRACTICE NEUROLOGY LA English DT Editorial Material C1 Amer Acad Neurol, St Paul, MN 55116 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Yale Univ, Sch Med, Dept Neurol, New Haven, CT USA. RP Henson, JW (reprint author), Amer Acad Neurol, St Paul, MN 55116 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1745-834X J9 NAT CLIN PRACT NEURO JI Nat. Clin. Pract. Neurol. PD NOV PY 2007 VL 3 IS 11 BP 589 EP 589 DI 10.1038/ncpneuro0636 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 225JA UT WOS:000250513000001 PM 17982430 ER PT J AU Hillbertz, NHCS Isaksson, M Karlsson, EK Hellmen, E Pielberg, GR Savolainen, P Wade, CM Von Euler, H Gustafson, U Hedhammar, K Nilsson, M Lindblad-Toh, K Andersson, L Andersson, G AF Hillbertz, Nicolette H. C. Salmon Isaksson, Magnus Karlsson, Elinor K. Hellmen, Eva Pielberg, Gerli Rosengren Savolainen, Peter Wade, Claire M. Von Euler, Henrik Gustafson, Ulla Hedhammar, Ake Nilsson, Mats Lindblad-Toh, Kerstin Andersson, Leif Andersson, Goran TI Duplication of FGF3, FGF4, FGF19 and ORAOV1 causes hair ridge and predisposition to dermoid sinus in Ridgeback dogs SO NATURE GENETICS LA English DT Article ID EXPRESSION; CELLS; GENE AB The dorsal hair ridge in Rhodesian and Thai Ridgeback dogs is caused by a dominant mutation that also predisposes to the congenital developmental disorder dermoid sinus. Here we show that the causative mutation is a 133-kb duplication involving three fibroblast growth factor (FGF) genes. FGFs play a crucial role in development, suggesting that the ridge and dermoid sinus are caused by dysregulation of one or more of the three FGF genes during development. C1 Swedish Univ Agr Sci, Ctr Biomed, Dept Anim Breeding & Genet, SE-75124 Uppsala, Sweden. Uppsala Univ, Rudbeck Lab, Dept Genet & Pathol, SE-75185 Uppsala, Sweden. Broad Inst Harvard, Cambridge, MA 02142 USA. MIT, Cambridge, MA 02142 USA. Boston Univ, Bioinformat Program, Boston, MA 02215 USA. SLU, Dept Physiol Anat & Biochem, SE-75007 Uppsala, Sweden. Uppsala Univ, Dept Med Biochem & Microbiol, SE-75124 Uppsala, Sweden. AlbaNova Univ Ctr, Royal Inst Technol, Sch Biotechnol, SE-10691 Stockholm, Sweden. Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. SLU, Dept Clin Sci, SE-75007 Uppsala, Sweden. RP Andersson, L (reprint author), Swedish Univ Agr Sci, Ctr Biomed, Dept Anim Breeding & Genet, Box 597, SE-75124 Uppsala, Sweden. EM leif.andersson@imbim.uu.se; goran.andersson@hgen.slu.se OI Karlsson, Elinor/0000-0002-4343-3776 NR 15 TC 94 Z9 95 U1 0 U2 31 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD NOV PY 2007 VL 39 IS 11 BP 1318 EP 1320 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 226GM UT WOS:000250575900015 ER PT J AU Karlsson, EK Baranowska, I Wade, CM Salmon Hillbertz, NHC Zody, MC Anderson, N Biagi, TM Patterson, N Pielberg, GR Kulbokas, EJ Comstock, KE Keller, ET Mesirov, JP von Euler, H Kampe, O Hedhammar, A Lander, ES Andersson, R Andersson, L Lindblad-Toh, K AF Karlsson, Elinor K. Baranowska, Izabella Wade, Claire M. Salmon Hillbertz, Nicolette H. C. Zody, Michael C. Anderson, Nathan Biagi, Tara M. Patterson, Nick Pielberg, Gerli Rosengren Kulbokas, Edward J., III Comstock, Kenine E. Keller, Evan T. Mesirov, Jill P. von Euler, Henrik Kampe, Olle Hedhammar, Ake Lander, Eric S. Andersson, Ran Andersson, Leif Lindblad-Toh, Kerstin TI Efficient mapping of mendelian traits in dogs through genome-wide association SO NATURE GENETICS LA English DT Article ID TRANSCRIPTION FACTOR GENE; WAARDENBURG-SYNDROME; DOMESTIC DOG; MITF; DIFFERENTIATION; PIGMENTATION; INHERITANCE; NEURULATION; MELANOCYTES; REGULATOR AB With several hundred genetic diseases and an advantageous genome structure, dogs are ideal for mapping genes that cause disease. Here we report the development of a genotyping array with similar to 27,000 SNPs and show that genome-wide association mapping of mendelian traits in dog breeds can be achieved with only similar to 20 dogs. Specifically, we map two traits with mendelian inheritance: the major white spotting ( S) locus and the hair ridge in Rhodesian ridgebacks. For both traits, we map the loci to discrete regions of <1 Mb. Fine-mapping of the S locus in two breeds refines the localization to a region of similar to 100 kb contained within the pigmentation-related gene MITF. Complete sequencing of the white and solid haplotypes identifies candidate regulatory mutations in the melanocyte-specific promoter of MITF. Our results show that genome-wide association mapping within dog breeds, followed by fine-mapping across multiple breeds, will be highly efficient and generally applicable to trait mapping, providing insights into canine and human health. C1 MIT, Broad Inst Harvard, Cambridge, MA 02142 USA. Boston Univ, Bioinformat Program, Boston, MA 02215 USA. Swedish Univ Agr Sci, Dept Anim Breeding & Genet, Biomed Ctr, SE-75124 Uppsala, Sweden. Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. Uppsala Univ, Dept Med Biochem, SE-75124 Uppsala, Sweden. Univ Michigan, Dept Urol, Ann Arbor, MI 48109 USA. Swedish Univ Agr Sci, Dept Clin Sci, SE-75007 Uppsala, Sweden. Uppsala Univ, Univ Hosp, Dept Med Sci, SE-75185 Uppsala, Sweden. Whitehead Inst Biomed Res, Cambridge, MA 02142 USA. MIT, Dept Biol, Cambridge, MA 02139 USA. Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. RP Karlsson, EK (reprint author), MIT, Broad Inst Harvard, 7 Cambridge Ctr, Cambridge, MA 02142 USA. EM elinor@broad.mit.edu; leif.andersson@imbim.uu.se; kersli@broad.mit.edu RI Keller, Evan/M-1446-2016; OI Keller, Evan/0000-0002-7592-7535; Kampe, Olle/0000-0001-6091-9914; Karlsson, Elinor/0000-0002-4343-3776; Wade, Claire/0000-0003-3413-4771 NR 36 TC 280 Z9 288 U1 11 U2 66 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD NOV PY 2007 VL 39 IS 11 BP 1321 EP 1328 DI 10.1038/ng.2007.10 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 226GM UT WOS:000250575900016 PM 17906626 ER PT J AU Pujana, MA Han, JDJ Starita, LM Stevens, KN Tewari, M Ahn, JS Rennert, G Moreno, V Kirchhoff, T Gold, B Assmann, V ElShamy, WM Rual, JF Levine, D Rozek, LS Gelman, RS Gunsalus, KC Greenberg, RA Sobhian, B Bertin, N Venkatesan, K Ayivi-Guedehoussou, N Sole, X Hernandez, P Lazaro, C Nathanson, KL Weber, BL Cusick, ME Hill, DE Offit, K Livingston, DM Gruber, SB Parvin, JD Vidal, M AF Pujana, Miguel Angel Han, Jing-Dong J. Starita, Lea M. Stevens, Kristen N. Tewari, Muneesh Ahn, Jin Sook Rennert, Gad Moreno, Victor Kirchhoff, Tomas Gold, Bert Assmann, Volker ElShamy, Wael M. Rual, Jean-Francois Levine, Douglas Rozek, Laura S. Gelman, Rebecca S. Gunsalus, Kristin C. Greenberg, Roger A. Sobhian, Bijan Bertin, Nicolas Venkatesan, Kavitha Ayivi-Guedehoussou, Nono Sole, Xavier Hernandez, Pilar Lazaro, Conxi Nathanson, Katherine L. Weber, Barbara L. Cusick, Michael E. Hill, David E. Offit, Kenneth Livingston, David M. Gruber, Stephen B. Parvin, Jeffrey D. Vidal, Marc TI Network modeling links breast cancer susceptibility and centrosome dysfunction SO NATURE GENETICS LA English DT Article ID CAENORHABDITIS-ELEGANS; C-ELEGANS; GENETIC INSTABILITY; ZYG-9 FORM; PROTEIN; BRCA1; AMPLIFICATION; MUTATIONS; COMPLEX; TAC-1 AB Many cancer-associated genes remain to be identified to clarify the underlying molecular mechanisms of cancer susceptibility and progression. Better understanding is also required of how mutations in cancer genes affect their products in the context of complex cellular networks. Here we have used a network modeling strategy to identify genes potentially associated with higher risk of breast cancer. Starting with four known genes encoding tumor suppressors of breast cancer, we combined gene expression profiling with functional genomic and proteomic ( or `omic') data from various species to generate a network containing 118 genes linked by 866 potential functional associations. This network shows higher connectivity than expected by chance, suggesting that its components function in biologically related pathways. One of the components of the network is HMMR, encoding a centrosome subunit, for which we demonstrate previously unknown functional associations with the breast cancer associated gene BRCA1. Two case-control studies of incident breast cancer indicate that the HMMR locus is associated with higher risk of breast cancer in humans. Our network modeling strategy should be useful for the discovery of additional cancer-associated genes. C1 Harvard Univ, Sch Med, CCSB, Dept Genet, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA. Carmel Hosp, Dept Community Med & Epidemiol, CHS Natl Canc Control Ctr, IL-34362 Haifa, Israel. Technion, Bruce Rappaport Fac Med, IL-34362 Haifa, Israel. Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. IDIBELL, Catalan Inst Oncol, Dept Epidemiol, Barcelona 08907, Spain. IDIBELL, Catalan Inst Oncol, Canc Registry, Barcelona 08907, Spain. IDIBELL, Catalan Inst Oncol, Translat Res Lab, Barcelona 08907, Spain. Mem Sloan Kettering Canc Ctr, Dept Med, Clin Genet Serv, New York, NY 10021 USA. Natl Canc Inst, Human Genet Sect, Lab Genome Divers, Frederick, MD 21702 USA. Univ Hamburg, Hosp Eppendorf, Inst Tumor Biol, Ctr Med Expt, D-20246 Hamburg, Germany. Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. NYU, Dept Biol, Ctr Comparat Funct Genom, New York, NY 10003 USA. IDIBELL, Catalan Inst Oncol, Translat Res Lab, Barcelona 08907, Spain. Univ Penn, Sch Med, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA. Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA. RP Pujana, MA (reprint author), Harvard Univ, Sch Med, CCSB, Dept Genet, 44 Binney St, Boston, MA 02115 USA. RI Bertin, Nicolas/C-3025-2008; Moreno, Victor/A-1697-2010; Parvin, Jeffrey/C-8955-2009; Hill, David/B-6617-2011; pujana, Miguel Angel/N-3127-2014; OI Bertin, Nicolas/0000-0002-9835-9606; Kirchhoff, Tomas/0000-0002-9055-2364; Moreno, Victor/0000-0002-2818-5487; pujana, Miguel Angel/0000-0003-3222-4044; Sole, Xavier/0000-0002-2197-3325; Rual, Jean-Francois/0000-0003-4465-8819; Nathanson, Katherine/0000-0002-6740-0901 FU NCI NIH HHS [P30 CA046592, CA90281] NR 50 TC 315 Z9 335 U1 2 U2 24 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD NOV PY 2007 VL 39 IS 11 BP 1338 EP 1349 DI 10.1038/ng.2007.2 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 226GM UT WOS:000250575900018 PM 17922014 ER PT J AU Xu, N Donohoe, ME Silva, SS Lee, JT AF Xu, Na Donohoe, Mary E. Silva, Susana S. Lee, Jeannie T. TI Evidence that homologous X-chromosome pairing requires transcription and Ctcf protein SO NATURE GENETICS LA English DT Article ID XIST GENE; CHROMATIN CONFORMATION; INACTIVATION CHOICE; TSIX TRANSCRIPTION; METHYLATION; RNA; COLOCALIZATION; IDENTIFICATION; NUCLEUS; BINDING AB X-chromosome inactivation (XCI) ensures the equality of X-chromosome dosages in male and female mammals by silencing one X in the female(1). To achieve the mutually exclusive designation of active X (Xa) and inactive X ( Xi), the process necessitates that two Xs communicate in trans through homologous pairing(2,3). Pairing depends on a 15-kb region within the genes Tsix and Xite(2). Here, we dissect molecular requirements and find that pairing can be recapitulated by 1- to 2-kb subfragments of Tsix or Xite with little sequence similarity. However, a common denominator among them is the presence of the protein Ctcf, a chromatin insulator(4-7) that we find to be essential for pairing. By contrast, the Ctcf-interacting partner, Yy1 (ref. 8), is not required. Pairing also depends on transcription. Transcriptional inhibition prevents new pair formation but does not perturb existing pairs. The kinetics suggest a pairing half-life of < 1 h. We propose that pairing requires Ctcf binding and co-transcriptional activity of Tsix and Xite. C1 Harvard Univ, Sch Med,Dept Genet, Massachusetts Gen Hosp, Dept Mol Biol,Howard Hughes Med Inst, Boston, MA 02114 USA. Programme Biomed, P-2780156 Oeiras, Portugal. RP Lee, JT (reprint author), Harvard Univ, Sch Med,Dept Genet, Massachusetts Gen Hosp, Dept Mol Biol,Howard Hughes Med Inst, Boston, MA 02114 USA. EM lee@molbio.mgh.harvard.edu FU NIGMS NIH HHS [R01-GM58839] NR 30 TC 129 Z9 132 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD NOV PY 2007 VL 39 IS 11 BP 1390 EP 1396 DI 10.1038/ng.2007.5 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 226GM UT WOS:000250575900024 PM 17952071 ER PT J AU Kaufmann, DE Kavanagh, DG Pereyra, F Zaunders, JJ Mackey, EW Miura, T Palmer, S Brockman, M Rathod, A Piechocka-Trocha, A Baker, B Zhu, B Le Gall, S Waring, MT Ahern, R Moss, K Kelleher, AD Coffin, JM Freeman, GJ Rosenberg, ES Walker, BD AF Kaufmann, Daniel E. Kavanagh, Daniel G. Pereyra, Florencia Zaunders, John J. Mackey, Elizabeth W. Miura, Toshiyuki Palmer, Sarah Brockman, Mark Rathod, Almas Piechocka-Trocha, Alicja Baker, Brett Zhu, Baogong Le Gall, Sylvie Waring, Michael T. Ahern, Ryan Moss, Kristin Kelleher, Anthony D. Coffin, John M. Freeman, Gordon J. Rosenberg, Eric S. Walker, Bruce D. TI Upregulation of CTLA-4 by HIV-specific CD4(+) T cells correlates with disease progression and defines a reversible immune dysfunction SO NATURE IMMUNOLOGY LA English DT Article ID INFECTED INDIVIDUALS; METASTATIC MELANOMA; ANTIGEN-4 BLOCKADE; TGF-BETA; IN-VITRO; EXPRESSION; RESPONSES; SUPPRESSION; PD-1; ACTIVATION AB In progressive viral infection, antiviral T cell function is impaired by poorly understood mechanisms. Here we report that the inhibitory immunoregulatory receptor CTLA-4 was selectively upregulated in human immunodeficiency virus (HIV)-specific CD4(+) T cells but not CD8(+) T cells in all categories of HIV-infected subjects evaluated, with the exception of rare people able to control viremia in the absence of antiretroviral therapy. CTLA-4 expression correlated positively with disease progression and negatively with the capacity of CD4(+) T cells to produce interleukin 2 in response to viral antigen. Most HIV-specific CD4(+) T cells coexpressed CTLA-4 and another inhibitory immunoregulatory receptor, PD-1. In vitro blockade of CTLA-4 augmented HIV-specific CD4(+) T cell function. These data, indicating a reversible immunoregulatory pathway selectively associated with CD4(+) T cell dysfunction, provide a potential target for immunotherapy in HIV-infected patients. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div AIDS, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. St Vincents Hosp, Ctr Immunol, Darlinghurst, NSW 2010, Australia. Howard Hughes Med Inst, Chevy Chase, MD 20185 USA. NCI, HIV Drug Resistance Program, NIH, Frederick, MD 21702 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol,Dept Med, Boston, MA 02115 USA. RP Kaufmann, DE (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02115 USA. EM dkaufmann@partners.org RI Zaunders, John/J-6553-2012 OI Zaunders, John/0000-0002-5912-5989 FU NHLBI NIH HHS [R01 HL092565]; NIAID NIH HHS [F32 AI058457, P30 AI060354] NR 46 TC 265 Z9 276 U1 1 U2 17 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD NOV PY 2007 VL 8 IS 11 BP 1246 EP 1254 DI 10.1038/ni1515 PG 9 WC Immunology SC Immunology GA 222ZR UT WOS:000250338900017 PM 17906628 ER PT J AU Ceol, CJ Pellman, D Zon, LI AF Ceol, Craig J. Pellman, David Zon, Leonard I. TI APC and colon cancer: two hits for one SO NATURE MEDICINE LA English DT Editorial Material ID COLORECTAL-CANCER; TUMORIGENESIS; POLYPLOIDY; PATHWAY; CELLS C1 Harvard Univ, Childrens Hosp, Sch Med,Dana Farber Canc Inst, Howard Hughes Med Inst,Stem Cell Program, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Sch Med,Dana Farber Canc Inst, Howard Hughes Med Inst,Div Hematol Oncol, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Sch Med,Dana Farber Canc Inst, Dept Pediat, Boston, MA 02115 USA. Harvard Univ, Childrens Hosp, Sch Med, Dept Pediat Hematol Oncol, Boston, MA 02115 USA. RP Ceol, CJ (reprint author), Harvard Univ, Childrens Hosp, Sch Med,Dana Farber Canc Inst, Howard Hughes Med Inst,Stem Cell Program, Boston, MA 02115 USA. EM zon@enders.tch.harvard.edu NR 15 TC 7 Z9 7 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD NOV PY 2007 VL 13 IS 11 BP 1286 EP 1287 DI 10.1038/nm1107-1286 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 228NP UT WOS:000250736900016 PM 17987022 ER PT J AU Scholz, J Woolf, CJ AF Scholz, Joachim Woolf, Clifford J. TI The neuropathic pain triad: Neurons, immune cells and glia SO NATURE NEUROSCIENCE LA English DT Review ID PERIPHERAL-NERVE INJURY; DORSAL-ROOT GANGLION; MONOCYTE CHEMOATTRACTANT PROTEIN-1; NECROSIS-FACTOR-ALPHA; CHRONIC CONSTRICTION INJURY; RAT SCIATIC-NERVE; RANDOMIZED CONTROLLED-TRIAL; PRIMARY SENSORY NEURONS; SPINAL-CORD MICROGLIA; WALLERIAN DEGENERATION AB Nociceptive pain results from the detection of intense or noxious stimuli by specialized high-threshold sensory neurons (nociceptors), a transfer of action potentials to the spinal cord, and onward transmission of the warning signal to the brain. In contrast, clinical pain such as pain after nerve injury (neuropathic pain) is characterized by pain in the absence of a stimulus and reduced nociceptive thresholds so that normally innocuous stimuli produce pain. The development of neuropathic pain involves not only neuronal pathways, but also Schwann cells, satellite cells in the dorsal root ganglia, components of the peripheral immune system, spinal microglia and astrocytes. As we increasingly appreciate that neuropathic pain has many features of a neuroimmune disorder, immunosuppression and blockade of the reciprocal signaling pathways between neuronal and non-neuronal cells offer new opportunities for disease modification and more successful management of pain. C1 Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Dept Anesthesia & Crit Care, Nueral Plast Res Grp, Charlestown, MA 02129 USA. RP Scholz, J (reprint author), Harvard Univ, Sch Med, 149 13th St,Room 4309, Charlestown, MA 02129 USA. EM scholz.joachim@mgh.harvard.edu NR 100 TC 734 Z9 769 U1 20 U2 148 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD NOV PY 2007 VL 10 IS 11 BP 1361 EP 1368 DI 10.1038/nn1992 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 225HT UT WOS:000250508400010 PM 17965656 ER PT J AU Call, ME Wucherpfennig, KW AF Call, Matthew E. Wucherpfennig, Kai W. TI Common themes in the assembly and architecture of activating immune receptors SO NATURE REVIEWS IMMUNOLOGY LA English DT Review ID T-CELL-RECEPTOR; TRANSMEMBRANE HELICAL INTERACTIONS; ZETA-CHAIN DIMERIZATION; NATURAL-KILLER-CELLS; ANTIGEN RECEPTOR; SIGNAL-TRANSDUCTION; SURFACE EXPRESSION; TCR/CD3 COMPLEX; CD3-EPSILON-GAMMA HETERODIMER; ERYTHROPOIETIN RECEPTOR AB Each of the many different cell types of the immune system expresses one or several activating receptors which serve a central role in the cell's surveillance function. Many of these cell-surface receptors share a distinctive modular design that consists of a ligand-binding module with no intrinsic signalling capability that is non-covalently associated with one or more dimeric signalling modules. Receptor assembly is directed by unique polar contacts within the transmembrane domains, whereas extracellular contacts can contribute to stability and specificity. This Review discusses the structural basis of receptor assembly and the implications of these findings for the mechanisms of receptor triggering. C1 Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. Harvard Univ, Sch Med, Program Immunol, Boston, MA USA. Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA USA. RP Wucherpfennig, KW (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. EM kai_wucherpfennig@dfci.harvard.edu OI Call, Matthew/0000-0001-5846-6469 FU NIAID NIH HHS [R01 AI054520] NR 108 TC 59 Z9 61 U1 1 U2 12 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1733 J9 NAT REV IMMUNOL JI Nat. Rev. Immunol. PD NOV PY 2007 VL 7 IS 11 BP 841 EP 850 DI 10.1038/nri2186 PG 10 WC Immunology SC Immunology GA 224KA UT WOS:000250444700011 PM 17960150 ER PT J AU Yuan, PQ Million, M Wu, SV Rivier, J Tache, Y AF Yuan, P. -Q. Million, M. Wu, S. V. Rivier, J. Tache, Y. TI Peripheral corticotropin releasing factor (CRF) and a novel CRF1 receptor agonist, stressin(1)-A activate CRF1 receptor expressing cholinergic and nitrergic myenteric neurons selectively in the colon of conscious rats SO NEUROGASTROENTEROLOGY AND MOTILITY LA English DT Article DE colonic motility; corticotropin releasing factor; CRF1 receptor; enteric nervous system; Fos; peripheral choline acetyltransferase; stressin(1)-A ID ENTERIC NERVOUS-SYSTEM; GIANT MIGRATING CONTRACTIONS; IRRITABLE-BOWEL-SYNDROME; FOS EXPRESSION; GUINEA-PIG; SIGNALING PATHWAYS; TYPE-1 RECEPTOR; MESSENGER-RNA; BRAIN-STEM; C-FOS AB Intraperitoneal (i.p.)corticotropin releasing factor (CRF) induced a CRF1 receptor-dependent stimulation of myenteric neurons and motility in the rat proximal colon. We characterize the colonic enteric nervous system response to CRF in conscious rats. Laser capture microdissection combined with reverse transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry in longitudinal muscle myenteric plexus whole-mount colonic preparations revealed CRF1 receptor expression in myenteric neurons. CRF (i.p., 10 mu g kg(-1)) induced Fos immunoreactivity (IR) (cells per ganglion) selectively in myenteric plexus of proximal (18.3 +/- 2.4 vs vehicle: 0.0 +/- 0.0) and distal colon (16.8 +/- 1.2 vs vehicle: 0.0 +/- 0.0), but not in that of gastric corpus, antrum, duodenum, jejunum and ileum. The selective CRF1 agonist, stressin(1)-A (i.p., 10 mu g kg(-1)) also induced Fos IR in myenteric but not in submucosal plexus of the proximal and distal colon. Fos IR induced by CRF was located in 55 +/- 1.9% and 53 +/- 5.1% of CRF1 receptor-IR myenteric neurons and in 44 +/- 2.8% and 40 +/- 3.9% of cholinergic neurons with Dogiel type I morphology, and in 20 +/- 1.6% and 80 +/- 3.3% of nitrergic neurons in proximal and distal colon respectively. CRF and stressin(1)-A elicit defecation and diarrhoea. These data support that one mechanism through which peripherally injected CRF ligands stimulate colonic function involves a direct action on colonic cholinergic and nitrergic myenteric neurons expressing CRF1 receptor. C1 Univ Calif Los Angeles, CURE Digest Dis Res Ctr, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Ctr Neurovisceral Sci & Womens Hlth, VA Greater Los Angeles Healthcare Syst, Div Digest Dis,Dept Med, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90073 USA. Salk Inst Biol Studies, Clayton Fdn Labs Prot Biol, La Jolla, CA 92037 USA. RP Yuan, PQ (reprint author), Bldg 115,Rm 217,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM pqyuan@mednet.ucla.edu FU NIDDK NIH HHS [R21 DK-068155, P01 DK 026741, DK 41301, R01 DK- 57238] NR 65 TC 44 Z9 45 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1350-1925 J9 NEUROGASTROENT MOTIL JI Neurogastroenterol. Motil. PD NOV PY 2007 VL 19 IS 11 BP 923 EP 936 DI 10.1111/j.1365-2982.2007.00978.x PG 14 WC Gastroenterology & Hepatology; Clinical Neurology; Neurosciences SC Gastroenterology & Hepatology; Neurosciences & Neurology GA 228KU UT WOS:000250729600008 PM 17973638 ER PT J AU Stufflebeam, SM Rosen, BR AF Stufflebeam, Steven M. Rosen, Bruce R. TI Mapping cognitive function SO NEUROIMAGING CLINICS OF NORTH AMERICA LA English DT Review ID AUDITORY SENSORY MEMORY; DORSOLATERAL PREFRONTAL CORTEX; OSCILLATORY GAMMA-ACTIVITY; IMAGE-GUIDED NEUROSURGERY; MAGNETIC BRAIN RESPONSES; SHORT-TERM-MEMORY; MISMATCH NEGATIVITY; ALZHEIMERS-DISEASE; WHITE-MATTER; SELECTIVE-ATTENTION AB Cognitive functions are fundamental to being human. Although tremendous progress has been made in the science of cognition using neuroimaging, the clinical applications of neuroimaging are just beginning to be realized. This article focuses on selected technologies, analysis techniques, and applications that have, or will soon have, direct clinical impact. The authors discuss how cognition can be imaged using MR imaging, functional MR imaging, positron emission tomography, magnetoencephalography and electroencephalography, and MR imaging diffusion tensor imaging. A unifying theme of this article is the concept that a more complete understanding of cognition only comes through integration of multimodal structural and functional imaging technologies. C1 Massachusetts Gen Hosp, Harvard Med Sch, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. RP Stufflebeam, SM (reprint author), Massachusetts Gen Hosp, Harvard Med Sch, Athinoula A Martinos Ctr Biomed Imaging, Bldg 149,13th St, Charlestown, MA 02129 USA. EM sms@nmr.mgh.harvard.edu FU NCRR NIH HHS [P41RR14074]; NIMH NIH HHS [K08 MH067966-05, K08 MH067966-03, K08 MH067966-04, K08 MH067966, K08 MH067966-02, K08 MH067966-01A2]; NINDS NIH HHS [R01 NS037462, NS37462, R56 NS037462, R01 NS044623, NS44623] NR 121 TC 8 Z9 9 U1 1 U2 7 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1052-5149 J9 NEUROIMAG CLIN N AM JI Neuroimaging Clin. N. Am. PD NOV PY 2007 VL 17 IS 4 BP 469 EP + DI 10.1016/j.nic.2007.07.005 PG 18 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 236OT UT WOS:000251313300009 PM 17983964 ER PT J AU Sauvageot, CM Kesari, S Stiles, CD AF Sauvageot, Claire M. Kesari, Santosh Stiles, Charles D. TI Molecular pathogenesis of adult brain tumors and the role of stem cells SO NEUROLOGIC CLINICS LA English DT Review ID EPIDERMAL-GROWTH-FACTOR; PRIMITIVE NEUROECTODERMAL TUMORS; CENTRAL-NERVOUS-SYSTEM; SUPPRESSOR GENE-PRODUCT; HUMAN-MALIGNANT GLIOMAS; COMPARATIVE GENOMIC HYBRIDIZATION; CONFERS ENHANCED TUMORIGENICITY; NEURAL STEM/PROGENITOR CELLS; PEDIATRIC-ONCOLOGY-GROUP; HUMAN GLIOBLASTOMA CELLS AB Primary brain tumors consist of neoplasms with varied molecular defects, morphologic phenotypes, and clinical outcomes. The genetic and signaling abnormalities involved in tumor initiation and progression of the most prevalent adult primary brain tumors, including gliomas, meningiomas, and medulloblastomas, are described in this article. The current understanding of the cell-of-origin of these neoplasms is reviewed, which suggests that the malignant phenotype is propelled by cells with stem-like qualities. A comprehensive understanding of the molecular basis of transformation and the cell-of-origin of these neoplasms will enable the formulation of more targeted treatment alternatives that could improve survival and quality of life. C1 Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. Harvard Med sch, Boston, MA 02115 USA. Brigham & Womens Canc Ctr, Ctr Neuro Oncol, Boston, MA 02115 USA. RP Stiles, CD (reprint author), Dana Farber Canc Inst, Dept Canc Biol, 44 Binney St, Boston, MA 02115 USA. EM charles_stiles@dfci.harvard.edu RI Kesari, Santosh/E-8461-2013 NR 272 TC 27 Z9 27 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 0733-8619 J9 NEUROL CLIN JI Neurol. Clin. PD NOV PY 2007 VL 25 IS 4 BP 891 EP + DI 10.1016/j.ncl.2007.07.014 PG 35 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 236OV UT WOS:000251313500003 PM 17964020 ER PT J AU Farrell, CJ Plotkin, SR AF Farrell, Christopher J. Plotkin, Scott R. TI Genetic causes of brain tumors: Neurofibromatosis, tuberous sclerosis, von Hippel-Lindau, and other syndromes SO NEUROLOGIC CLINICS LA English DT Article ID CELL CARCINOMA SYNDROME; LI-FRAUMENI-SYNDROME; LHERMITTE-DUCLOS-DISEASE; BILATERAL ACOUSTIC NEUROFIBROMATOSIS; GENOTYPE-PHENOTYPE CORRELATIONS; STEREOTACTIC RADIOTHERAPY FSRT; CENTRAL-NERVOUS-SYSTEM; NF1 GENE; VESTIBULAR-SCHWANNOMA; CONSENSUS CONFERENCE AB Several familial syndromes are associated with an increased incidence of nervous system tumors. Recognition of these syndromes is critical to provide optimal clinical care and genetic counseling to affected patients and their families. Identification of the genetic defects responsible for these relatively uncommon disorders has led to the improved understanding of critical molecular pathways involved in tumorigenesis and has contributed to the emergence of molecularly targeted therapeutics against cancer. The hereditary syndromes and diseases included in this review are limited to those associated with brain tumors: neurofibromatosis 1, neurofibromatosis 2, tuberous sclerosis complex, von Hippel-Lindau disease, and the less frequently encountered Cowden disease and Li-Fraumeni, Turcot's, and Gorlin's syndromes. C1 Pappas Ctr Neuro Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Plotkin, SR (reprint author), Pappas Ctr Neuro Oncol, Yawkey 9E,55 Fruit St, Boston, MA 02114 USA. EM splotkin@partners.org NR 85 TC 42 Z9 42 U1 0 U2 7 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0733-8619 EI 1557-9875 J9 NEUROL CLIN JI Neurol. Clin. PD NOV PY 2007 VL 25 IS 4 BP 925 EP + DI 10.1016/j.ncl.2007.07.008 PG 23 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 236OV UT WOS:000251313500004 PM 17964021 ER PT J AU Drappatz, J Schiff, D Kesarl, S Norden, AD Wen, PY AF Drappatz, Jan Schiff, David Kesarl, Santosh Norden, Andrew D. Wen, Patrick Y. TI Medical management of brain tumor patients SO NEUROLOGIC CLINICS LA English DT Review ID MOLECULAR-WEIGHT HEPARIN; DEEP-VEIN THROMBOSIS; QUALITY-OF-LIFE; HIGH-GRADE GLIOMA; ENDOTHELIAL GROWTH-FACTOR; RECURRENT MALIGNANT GLIOMA; RECOMBINANT FACTOR VIIA; POSTOPERATIVE VENOUS THROMBOEMBOLISM; GLUCOCORTICOID-INDUCED OSTEOPOROSIS; INTERMITTENT PNEUMATIC COMPRESSION AB Brain tumors can present challenging medical problems. Seizures, periturnoral edema, venous thromboembolism, fatigue, and cognitive dysfunction can complicate the treatment of patients who have primary or metastatic brain tumors. Effective medical management results in decreased morbidity and mortality and improved quality of life for affected patients. C1 Dana Farber Brigham & Womens Canc Ctr, Ctr Neuro Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Neurol, Div Neuro Oncol, Boston, MA 02115 USA. Univ Virginia, Hlth Sci Ctr, Neuro Oncol Ctr, Charlottesville, VA 22908 USA. RP Drappatz, J (reprint author), Dana Farber Brigham & Womens Canc Ctr, Ctr Neuro Oncol, SW430D,44 Binney St, Boston, MA 02115 USA. EM jdrappatz@partners.org RI Kesari, Santosh/E-8461-2013 NR 240 TC 45 Z9 45 U1 0 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 0733-8619 J9 NEUROL CLIN JI Neurol. Clin. PD NOV PY 2007 VL 25 IS 4 BP 1035 EP + DI 10.1016/j.ncl.2007.07.015 PG 38 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 236OV UT WOS:000251313500008 PM 17964025 ER PT J AU Cavaliere, R Wen, PY Schiff, D AF Cavaliere, Robert Wen, Patrick Y. Schiff, David TI Novel therapies for malignant gliomas SO NEUROLOGIC CLINICS LA English DT Review ID ENDOTHELIAL GROWTH-FACTOR; PHASE-II TRIAL; BRAIN-TUMOR CONSORTIUM; RECURRENT GLIOBLASTOMA-MULTIFORME; HIGH-GRADE GLIOMA; TYROSINE KINASE INHIBITOR; CANCER-TREATMENT GROUP; MIXED ANAPLASTIC OLIGODENDROGLIOMA; CARMUSTINE PLUS O-6-BENZYLGUANINE; FARNESYL TRANSFERASE INHIBITORS AB The impact of cytotoxic therapies on the outcome of glioblastoma has been modest thus far. Yet it is clear that subsets of high-grade gliomas exist that are sensitive to treatment. Patients deemed resistant to the current standard approach may be selected for alternative therapies, thereby avoiding treatment toxicity from an ineffective treatment. The future of novel therapies lies in our understanding of the molecular biology of gliomas and their stem cells. Not only will this drive the development of new agents, it will also lead to tailored therapies for specific tumors. Yet much research is still needed at all levels, from the identification of molecular markers to the development and application of novel therapeutics. C1 Ohio State Univ, Div Neurooncol, Columbus, OH 43210 USA. Dana Farber Brigham & Womens Hosp, Ctr Neurooncol, Boston, MA 02115 USA. Univ Virginia, Hlth Sci Ctr, Neuro Oncol Ctr, Charlottesville, VA 22908 USA. RP Cavaliere, R (reprint author), Ohio State Univ, Div Neurooncol, 463 Means Hall,1654 Upham Dr, Columbus, OH 43210 USA. EM robert.cavaliere@osumc.edu NR 162 TC 8 Z9 18 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 0733-8619 J9 NEUROL CLIN JI Neurol. Clin. PD NOV PY 2007 VL 25 IS 4 BP 1141 EP + DI 10.1016/j.ncl.2007.07.012 PG 32 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 236OV UT WOS:000251313500012 PM 17964029 ER PT J AU Franklin, TR Wang, Z Wang, J Sciortino, N Harper, D Li, Y Ehrman, R Kampman, K O'Brien, CP Detre, JA Childress, AR AF Franklin, Teresa R. wang, Ze Wang, Jiongjiong Sciortino, Nathan Harper, Derek Li, Yin Ehrman, Ron Kampman, Kyle O'Brien, Charles P. Detre, John A. Childress, Anna Rose TI Limbic activation to cigarette smoking cues independent of nicotine withdrawal: A perfusion fMRI study SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE cigarette smoking; craving; neuroimaging; ventral striatum; amygdala; DLPFC ID INTERNATIONAL NEUROPSYCHIATRIC INTERVIEW; SUSTAINED-RELEASE BUPROPION; VENTRAL TEGMENTAL AREA; PREFRONTAL CORTEX; NUCLEUS-ACCUMBENS; DSM-IV; SMOKERS; ADDICTION; CESSATION; AVAILABILITY AB Exposure to cigarette smoking cues can trigger physiological arousal and desire to smoke. The brain substrates of smoking cue-induced craving (CIC) are beginning to be elucidated; however, it has been difficult to study this state independent of the potential contributions of pharmacological withdrawal from nicotine. Pharmacological withdrawal itself may have substantial effects on brain activation to cues, either by obscuring or enhancing it, and as CIC is not reduced by nicotine replacement strategies, its neuro-anatomical substrates may differ. Thus, characterizing CIC is critical for developing effective interventions. This study used arterial spin-labeled (ASL) perfusion fMRI, and newly developed and highly appetitive, explicit smoking stimuli, to examine neural activity to cigarette CIC in an original experimental design that strongly minimizes contributions from pharmacological withdrawal. Twenty-one smokers ( 12 females) completed smoking and nonsmoking cue fMRI sessions. Craving self-reports were collected before and after each session. SPM2 software was employed to analyze data. Blood flow ( perfusion) in a priori-selected regions was greater during exposure to smoking stimuli compared to nonsmoking stimuli (p < 0.01; corrected) in ventral striatum, amygdala, orbitofrontal cortex, hippocampus, medial thalamus, and left insula. Perfusion positively correlated with intensity of cigarette CIC in both the dorsolateral prefrontal cortex (r(2) = 0.54) and posterior cingulate (r(2) = 0.53). This pattern of activation that includes the ventral striatum, a critical reward substrate, and the interconnected amygdala, cingulate and OFC, is consistent with decades of animal research on the neural correlates of conditioned drug reward. C1 Univ Penn, Dept Psychiat, Addict Treatment Res Ctr, Philadelphia, PA 19104 USA. Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA. Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. Univ Penn, Philadelphia VA Med Ctr, Philadelphia, PA 19104 USA. RP Franklin, TR (reprint author), Univ Penn, Dept Psychiat, Addict Treatment Res Ctr, 3900 Chestnut St, Philadelphia, PA 19104 USA. EM franklin_t@mail.trc.upenn.edu RI Wang, Ze/A-1043-2007 FU NCRR NIH HHS [RR02305]; NIDA NIH HHS [R21 DA025882, 5-P60-DA-005186-18, DA015149, K01 DA 015426-011A1, K01 DA015426, P60 DA005186]; NINDS NIH HHS [NS045839]; PHS HHS [BCS-0224007] NR 46 TC 180 Z9 189 U1 1 U2 16 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD NOV PY 2007 VL 32 IS 11 BP 2301 EP 2309 DI 10.1038/sj.npp.1301371 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 221KL UT WOS:000250226000006 PM 17375140 ER PT J AU Campbell, EG AF Campbell, Eric G. TI Doctors and drug companies - Scrutinizing influential relationships SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Campbell, EG (reprint author), Massachusetts Gen Hosp, Inst Hlth Policy, Boston, MA 02114 USA. NR 3 TC 63 Z9 66 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 1 PY 2007 VL 357 IS 18 BP 1796 EP 1797 DI 10.1056/NEJMp078141 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 225OJ UT WOS:000250526900002 PM 17978288 ER PT J AU Fu, SS McFall, M Saxon, AJ Beckham, JC Carmody, TP Baker, DG Joseph, AM AF Fu, Steven S. McFall, Miles Saxon, Andrew J. Beckham, Jean C. Carmody, Timothy P. Baker, Dewleen G. Joseph, Anne M. TI Post-traumatic stress disorder and smoking: A systematic review SO NICOTINE & TOBACCO RESEARCH LA English DT Review ID VIETNAM COMBAT VETERANS; SUBSTANCE USE DISORDERS; CORTICOTROPIN-RELEASING-FACTOR; MENTAL-HEALTH-CARE; NICOTINE DEPENDENCE; CIGARETTE-SMOKING; NEW-YORK; RISK-FACTORS; PSYCHIATRIC-DISORDERS; TERRORIST ATTACKS AB We conducted a systematic review of what is known about the relationship between post-traumatic stress disorder (PTSD) and smoking to guide research on underlying mechanisms and to facilitate the development of evidence-based tobacco treatments for this population of smokers. We searched Medline, PsychINFO, and the Cochrane Central Register of Controlled Trials and identified 45 studies for review that presented primary data on PTSD and smoking. Smoking rates were high among clinical samples with PTSD (40%-86%) as well as nonclinical populations with PTSD (34%-61%). Most studies showed a positive relationship between PTSD and smoking and nicotine dependence, with odds ratios ranging between 2.04 and 4.52. Findings also suggest that PTSD, rather than trauma exposure itself, is more influential for increasing risk of smoking. A small but growing literature has examined psychological factors related to smoking initiation and maintenance and the overlapping neurobiology of PTSD and nicotine dependence. Observational studies indicate that smokers with PTSD have lower quit rates than do smokers without PTSD. Yet a few tobacco cessation treatment trials in smokers with PTSD have achieved quit rates comparable with controlled trials of smokers without mental disorders. In conclusion, the evidence points to a causal relationship between PTSD and smoking that may be bidirectional. Specific PTSD symptoms may contribute to smoking and disrupt cessation attempts. Intervention studies that test behavioral and pharmacological interventions designed specifically for use in patients with PTSD are needed to reduce morbidity and mortality in this population. C1 VA Med Ctr, Ctr Chron Dis Outcomes Res, Minneapolis, MN 55417 USA. Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA. Univ Washington, NW Network Mental Illness Res Educ & Clin Ctr, VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Durham VA Med Ctr, Durham, NC USA. Duke Univ, Med Ctr, Durham, NC USA. VISN 6 Mental Illness Res Educ & Clin Ctr, Durham, NC USA. Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. Vet Affairs Med Ctr, Mental Hlth Serv, San Francisco, CA 94121 USA. Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA. RP Fu, SS (reprint author), VA Med Ctr, Ctr Chron Dis Outcomes Res, 152-2E,1 Vet Dr, Minneapolis, MN 55417 USA. EM steven.fu@va.gov NR 89 TC 113 Z9 114 U1 2 U2 18 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1462-2203 J9 NICOTINE TOB RES JI Nicotine Tob. Res. PD NOV PY 2007 VL 9 IS 11 BP 1071 EP 1084 DI 10.1080/14622200701488418 PG 14 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA 236WS UT WOS:000251334700003 PM 17978982 ER PT J AU Gourcerol, G Coskun, T Craft, LS Mayer, JP Heiman, ML Wang, L Million, M Pierre, DH Tache, Y AF Gourcerol, Guillaume Coskun, Tamer Craft, Libbey S. Mayer, John P. Heiman, Mark L. Wang, Lixin Million, Mulugeta St.-Pierre, David H. Tache, Yvette TI Preproghrelin-derived peptide, obestatin, fails to influence food intake in lean or obese rodents SO OBESITY LA English DT Article DE ghrelin; gastric motility; high-fat diet; glucose; gut-brain axis ID CORTICOTROPIN-RELEASING-FACTOR; GROWTH-HORMONE-SECRETION; NERVOUS-SYSTEM; ENERGY-BALANCE; WEIGHT-GAIN; GHRELIN; RATS; MOTILITY; MICE; SOMATOSTATIN AB Objectives: Obestatin has been initially characterized as a new peptide derived from the ghrelin precursor, which suppresses food intake and inhibits the orexigenic and prokinetic actions of ghrelin when injected peripherally or centrally in lean mice. However, reproducing these data remains controversial. Reasons for the disparity may be the use of different doses, routes, and animal models. We aimed to investigate the effects of peripheral and intracisternal (IQ injection of obestatin on feeding, gastric motility, and blood glucose in rats as well as in diet-induced obese (DIO) mice. Research Methods and Procedures: Food intake and gastric emptying of a semi-liquid caloric meal were measured after intraperitoneal (IP) injection of obestatin in rats and DID mice. Gastric phasic motility and blood glucose were monitored in urethane-anesthetized rats after IC or intravenous (IV) injection of obestatin. Results: Obestatin injected intraperitoneally at doses ranging from 0. 1 to 3 mg/kg influenced neither acute food intake nor gastric emptying in rats. Obestatin injected intravenously at 0.3 or 3 mg/kg and IC at 7.5 or 30 mu g/rat modified neither fasted gastric phasic motility nor blood glucose levels, while ghrelin (30 mu g/kg, IV) increased and vagotomy suppressed gastric motility, and an oligosomatostatin analog (3 mu g/rat, IQ decreased blood glucose. Obestatin, injected intraperitoneally (0.3 mg/kg) in DID mice, did not alter feeding response to a fast, while urocortin 1 (10 mu g/kg, IP) induced a 73.3 % inhibition at 2 hours. Discussion: Our data demonstrate that peripheral administration of obestatin did not modify food intake in rats or obese mice or gastric motor function in rats. C1 [Gourcerol, Guillaume; Wang, Lixin; Million, Mulugeta; Tache, Yvette] Univ Calif Los Angeles, Ctr Ulcer Res & Educ CURE, Digest Dis Res Ctr, Ctr Neurovisceral Sci & Womens Hlth Dept Med, Los Angeles, CA USA. [Tache, Yvette] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Coskun, Tamer; Craft, Libbey S.; Mayer, John P.; Heiman, Mark L.] Lilly Corp Ctr, Lilly Res Labs, Indianapolis, IN 46285 USA. [St.-Pierre, David H.] Univ Montreal, Dept Nutr, Montreal, PQ H3C 3J7, Canada. RP Tache, Y (reprint author), Ctr Neurovisceral Sci & Womens Hlth, VA Greater Los Angeles Healthcare Syst, CURE Bldg 115,Room 117,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM ytache@mednet.ucla.edu FU NIDDK NIH HHS [DK-41,301, R01 DK-33,061] NR 42 TC 53 Z9 55 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1930-7381 J9 OBESITY JI Obesity PD NOV PY 2007 VL 15 IS 11 BP 2643 EP 2652 DI 10.1038/oby.2007.316 PG 10 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 243EX UT WOS:000251779000017 PM 18070755 ER PT J AU Burgio, KL Richter, HE Clements, RH Redden, DT Goode, PS AF Burgio, Kathryn L. Richter, Holly E. Clements, Ronald H. Redden, David T. Goode, Patricia S. TI Changes in urinary and fecal incontinence symptoms with weight loss surgery in morbidity obese women SO OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 33rd Annual Meeting of the Society-of-Gynecological-Surgeons CY APR 13, 2007 CL Orlando, FL SP Soc Gynecol Surg ID Y-GASTRIC-BYPASS; PROLAPSE; QUALITY; COHORT; LIFE AB Objective: To examine changes in the prevalence and severity of urinary incontinence (UI) and fecal incontinence in morbidly obese women undergoing laparoscopic weight loss surgery. Methods: In a prospective cohort study, 101 women (aged 20-55 years) with body mass index (BMI) of 40 or more underwent laparoscopic Roux-en-Y gastric bypass and were followed to 6 and 12 months. Presence, severity, and effect of UI were assessed using the Medical, Epidemiological, and Social Aspects of Aging Questionnaire, Urogenital Distress Inventory, and Incontinence Impact Questionnaire. Fecal incontinence was assessed by self-report of anal leakage. Results: Mean BMI decreased from 48.9 +/- 7.2 presurgery to 35.3 +/- 6.5 at 6 months and 30.2 +/- 5.7 at 12 months postsurgery. Prevalence of Ul decreased from 66.7% presurgery to 41.0% at 6 months and 37.0% at 12 months (P<.001; 95% confidence interval [CI] for change 18.640.0%). Reduction in prevalence of Ul was significantly tinent women who lost 18 or more BMI points, 71% regained urinary continence at 12 months. Medical, Epidemiological, and Social Aspects of Aging Questionnaire urge and stress scores decreased (both P<.001; 95% CI 0.5-1.85 and 2.71-5.34, respectively), as did scores on the Urogenital Distress Inventory (P<.001; 95% CI 8.3116.21) and Incontinence Impact Questionnaire (P<.001; 95% CI 4.71-14.60), indicating reduction in severity. Prevalence of fecal incontinence (solid or liquid stool) decreased from 19.4% to 9.1% at 6 months and 8.6% at 12 months (P=.018; 95% Cl 2.1-19.4%). Conclusion: Prevalence of Ul and fecal incontinence decreased after bariatric surgery. Magnitude of weight loss was associated with reduction in Ul prevalence, strengthening the inference that improvements are attributable to weight loss. C1 Univ Alabama, Birmingham VA Med Ctr, Ctr Geriatr Res Educ & Clin, Birmingham, AL 35294 USA. Univ Alabama, Dept Med, Div Gerontol Geriatr & Palliat Care, Birmingham, AL 35294 USA. Univ Alabama, Dept Obstet & Gynecol, Div Womens Pelv Med & Reconstruct Surg, Birmingham, AL 35294 USA. Univ Alabama, Dept Surg, Birmingham, AL 35294 USA. Univ Alabama, Dept Biostat, Birmingham, AL 35294 USA. RP Burgio, KL (reprint author), Univ Alabama, Birmingham VA Med Ctr, Ctr Geriatr Res Educ & Clin, 11G,700 S 19th St, Birmingham, AL 35294 USA. EM kburgio@aging.uab.edu FU NIDDK NIH HHS [DK068389] NR 26 TC 89 Z9 90 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD NOV PY 2007 VL 110 IS 5 BP 1034 EP 1040 DI 10.1097/01.AOG.0000285483.22898.9c PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 223HM UT WOS:000250360800014 PM 17978117 ER PT J AU Richardson, PG Mitsiades, CS Anderson, KC AF Richardson, Paul G. Mitsiades, Constantine S. Anderson, Kenneth C. TI Continued progress in treatment options for multiple myeloma: From past to present and future - The Ning/He/Dagher et al article reviewed SO ONCOLOGY-NEW YORK LA English DT Editorial Material ID THALIDOMIDE PLUS DEXAMETHASONE; HIGH-DOSE DEXAMETHASONE; PEGYLATED LIPOSOMAL DOXORUBICIN; PHASE-III; CHEMOTHERAPEUTIC-AGENTS; COMBINATION THERAPY; BORTEZOMIB; PATHOGENESIS; SENSITIVITY; APPROVAL C1 [Richardson, Paul G.; Mitsiades, Constantine S.; Anderson, Kenneth C.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Richardson, Paul G.; Mitsiades, Constantine S.; Anderson, Kenneth C.] Dana Faber Canc Inst, Boston, MA USA. NR 24 TC 0 Z9 0 U1 0 U2 0 PU P R R INC PI MELVILLE PA 48 SOUTH SERVICE RD, MELVILLE, NY 11747 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD NOV PY 2007 VL 21 IS 12 BP 1511 EP + PG 3 WC Oncology SC Oncology GA 270RU UT WOS:000253738700011 ER PT J AU Quang, TS Wallner, KE Herstein, PR Palo, BM Walker, JB Sutlief, S AF Quang, Tony S. Wallner, Kent E. Herstein, Paul R. Palo, B. Marie Walker, Joseph B. Sutlief, Steven TI Technologic evolution in the treatment of prostate cancer - Clinical, financial, and legal implications for managed care organizations SO ONCOLOGY-NEW YORK LA English DT Editorial Material ID RADICAL PROSTATECTOMY; RECTAL COMPLICATIONS; BRACHYTHERAPY; I-125; RISK; RADIOTHERAPY; MORBIDITY; PD-103; LIKELIHOOD; CARCINOMA C1 [Quang, Tony S.; Wallner, Kent E.; Herstein, Paul R.; Walker, Joseph B.; Sutlief, Steven] Univ Washington, Med Ctr, Dept Radiat Oncol,Radiat Oncol Serv, Dept Vet Affairs,Radiat Oncol Grp Hlth Cooperat, Seattle, WA 98195 USA. [Palo, B. Marie] Univ Calif Davis, Med Ctr, Dept Radiat Oncol, Sacramento, CA 95817 USA. RP Quang, TS (reprint author), VA Puget Sound Hlth Care Syst, 1660 S Columbian Way, Seattle, WA 98108 USA. NR 35 TC 2 Z9 2 U1 0 U2 0 PU P R R INC PI MELVILLE PA 48 SOUTH SERVICE RD, MELVILLE, NY 11747 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD NOV PY 2007 VL 21 IS 13 BP 1598 EP + PG 6 WC Oncology SC Oncology GA 270RV UT WOS:000253738800008 PM 18179049 ER PT J AU Moore, S Davidson, A Griffis, M Sommers, R Farber, D Viale, PH Smith, L AF Moore, Susan Davidson, Amy Griffis, Martha Sommers, Robin Farber, Dana Viale, Pamela Hallquist Smith, Linda TI Supporting evidence-based practice via an interactive website for nurses caring for patients with colorectal cancer SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 Canc Expertise, Chicago, IL USA. Hope Ctr Canc Care, Youngstown, OH USA. S Georgia Med Ctr, Pearlman Canc Ctr, Valdosta, GA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Meniscus Hlth Care Commun, W Conshohocken, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ONCOLOGY NURSING SOC PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD NOV PY 2007 VL 34 IS 6 MA 2488 BP 1239 EP 1239 PG 1 WC Oncology; Nursing SC Oncology; Nursing GA 230FW UT WOS:000250862600022 ER PT J AU Desjardins, AE Vakoc, BJ Tearney, GJ Bouma, BE AF Desjardins, Adrien E. Vakoc, Benjamin J. Tearney, Guillermo J. Bouma, Brett E. TI Backscattering spectroscopic contrast with angle-resolved optical coherence tomography SO OPTICS LETTERS LA English DT Article ID SCATTERING; ABSORPTION; PROFILES; SPECKLE AB Backscattering spectroscopic contrast using angle-resolved optical coherence tomography is demonstrated as a powerful method for determining scatterer diameter with subwavelength resolution. By applying spectroscopic digital processing algorithms to interferograms acquired in the frequency domain with a wavelength-swept laser centered at 1295 nm, it was shown that differences in wavelength-dependent backscattering from 0.3 and 1 mu m diameter microspheres can be clearly resolved. The observed backscattering spectra were found to be consistent with Mie theory. High levels of speckle noise reduction achieved by angular compounding increased the spatial resolution at which backscattering spectra could be accurately differentiated. (c) 2007 Optical Society of America C1 Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Desjardins, AE (reprint author), Harvard Univ, Sch Med, Boston, MA 02114 USA. EM adesjard@MIT.edu FU NCI NIH HHS [R01 CA103769, R01 CA103769-03]; NHLBI NIH HHS [R01 HL076398, R01 HL076398-05] NR 11 TC 7 Z9 7 U1 1 U2 6 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 0146-9592 J9 OPT LETT JI Opt. Lett. PD NOV 1 PY 2007 VL 32 IS 21 BP 3158 EP 3160 DI 10.1364/OL.32.003158 PG 3 WC Optics SC Optics GA 237CJ UT WOS:000251350100036 PM 17975629 ER PT J AU Wang, DY Gordon, BR Chan, YH Yeoh, KH AF Wang, De Yun Gordon, Bruce R. Chan, Yiong Huak Yeoh, Kian Hian TI Potential non-immunoglobulin E-mediated food allergies: Comparison of open challenge and double-blind placebo-controlled food challenge SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article ID ATOPIC ECZEMA/DERMATITIS SYNDROME; MILK ALLERGY; SKIN-PRICK; PATCH-TEST; DIAGNOSIS; HYPERSENSITIVITY; PROVOCATION; REACTIVITY; SYMPTOMS; CHILDREN AB OBJECTIVE: Comparison of open food challenge (OFC) with double-blind placebo-controlled food challenge (DBPCFC). STUDY DESIGN: Prospective sequential randomized challenges. METHODS: Twenty adults with chronic allergy symptoms and at least I positive intradermal food wheal response recorded symptoms during DBPCFC and OFC provoked using organic foods, normal portions, and normal food preparation. Acoustic Rhinometry and biochemical tests were done during DBPCFC. RESULTS: All patients reacted to at least I food and to all challenges with the same food, with multiorgan symptoms in the nose, nervous system, throat, and lung. There was a correlation in the type and severity of symptoms (P = 0.015) for OFC and DBPCFC, and both were significantly (P < 0.01) more severe than placebo. Compared with DBPCFC, OFC sensitivity was 66%, and positive predictive value was 89%. CONCLUSION: This is the first study showing both concordance of OFC and DBPCFC and also that intradermal tests can identify reactive foods that can be verified by DBPCFC. Because most tests for IgE-mediated food allergy were negative, observed reactions were probably non-IgE mediated. (C) 2007 American Academy of Otolaryngology-Head and Neck Surgery Foundation. All rights reserved. C1 Natl Univ Singapore, Dept Otolaryngol, Singapore, Singapore. Natl Univ Singapore, Dept Biostat, Singapore, Singapore. Harvard Univ, Massachusetts Eye & Ear Infirm, Dept Otol & Laryngol, Cambridge, MA 02138 USA. Cape Cod Hosp, Div Otolaryngol, Hyannis, MA USA. RP Gordon, BR (reprint author), Cape Cod ENT, 65 Cedar St, Hyannis, MA 02601 USA. EM docbruce@comcast.net NR 20 TC 4 Z9 4 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD NOV PY 2007 VL 137 IS 5 BP 803 EP 809 DI 10.1016/j.otohns.2007.06.714 PG 7 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 229RK UT WOS:000250821700021 ER PT J AU Zardkoohi, O Nandigam, V Murray, L Heist, EK Mela, T Orencole, M Ruskin, JN Singh, JP AF Zardkoohi, Omeed Nandigam, Veena Murray, Lorne Heist, E. Kevin Mela, Theofanie Orencole, Mary Ruskin, Jeremy N. Singh, Jagmeet P. TI The impact of age and gender on cardiac resynchronization therapy outcome SO PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY LA English DT Article DE age; gender; resynchronization; etiology; heart failure ID CONGESTIVE-HEART-FAILURE; MORTALITY; ENALAPRIL; MORBIDITY; SURVIVAL; TRIAL AB Background: Cardiac resynchronization therapy (CRT) outcome varies significantly among patients. We aimed to determine the impact of age, gender, and heart failure etiology on the long-term outcome of patients receiving CRT. Methods: A total of 117 patients with drug-refractory heart failure, New York Heart Association (NYHA) Class III or IV, and a wide QRS complex, who received CRT, were followed for one year. Long-term outcome was measured as a combined end point of hospitalization for heart failure and/or all cause mortality. Efficacy of CRT was compared between men and women, between older and younger patients, and between patients with ischemic and nonischemic heart disease. Time to the primary end point was estimated by the Kaplan-Meier method and comparisons were made using the Breslow-Wilcoxon test. Results: Baseline clinical characteristics were comparable between gender, age, and heart failure etiology subgroups. There was no significant difference in the combined end point between older versus younger (age >= 70, (n = 71), versus age < 70, (n = 46), P = 0.52); both genders (men, n = 91 vs women, n = 26, P = 0.46) and etiology of the cardiomyopathy (ischemic (n = 79) vs nonischemic (n = 38), P = 0.12). Substratification of the genders by the etiology of the cardiomyopathy, showed that women with ischemic cardiomyopathy (IW, n = 10) had a trend to a worse outcome compared to the other groups i.e., nonischemic women (NIW, n = 16), ischemic men (IM, n = 69), and nonischemic men (NIM, n = 22), P = 0.04. After adjusting for potential covariates, a Cox regression analysis showed no significant difference between the groups (P = 0.61). Conclusions: CRT outcome appears independent of age, gender, and heart failure etiology in this single institution study. C1 Harvard Univ, Massachusetts Gen Hosp, Dept Med, Cardiac Arrhythmia Serv,GRB 109, Boston, MA 02114 USA. RP Singh, JP (reprint author), Harvard Univ, Massachusetts Gen Hosp, Dept Med, Cardiac Arrhythmia Serv,GRB 109, 55 Fruit St, Boston, MA 02114 USA. EM jsingh@partners.org NR 16 TC 15 Z9 15 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0147-8389 J9 PACE JI PACE-Pacing Clin. Electrophysiol. PD NOV PY 2007 VL 30 IS 11 BP 1344 EP 1348 DI 10.1111/j.1540-8159.2007.00869.x PG 5 WC Cardiac & Cardiovascular Systems; Engineering, Biomedical SC Cardiovascular System & Cardiology; Engineering GA 225YE UT WOS:000250553400009 PM 17976097 ER PT J AU Borsook, D AF Borsook, D. TI Pain and motor system plasticity SO PAIN LA English DT Editorial Material ID TRANSCRANIAL MAGNETIC STIMULATION; SOMATOSENSORY CORTEX; INHIBITION; EXCITABILITY; MODULATION; AMPUTATION; THALAMUS; HUMANS C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat,McLean Hosp,Dept Psychiat & Radiol, Cambridge, MA 02138 USA. RP Borsook, D (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Psychiat,McLean Hosp,Dept Psychiat & Radiol, Cambridge, MA 02138 USA. EM dborsook@mclean.harvard.edu FU NINDS NIH HHS [R01 NS042721-04, R01 NS042721, R01 NS056195, R01 NS056195-03] NR 24 TC 10 Z9 11 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD NOV PY 2007 VL 132 IS 1-2 BP 8 EP 9 DI 10.1016/j.pain.2007.09.006 PG 2 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 232JO UT WOS:000251015400004 PM 17892913 ER PT J AU Fagenholz, PJ Castillo, CFD Harris, NS Pelletier, AJ Camargo, CA AF Fagenholz, Peter J. Castillo, Carlos Fernandez-del Harris, N. Stuart Pelletier, Andrea J. Camargo, Carlos A., Jr. TI Direct medical costs of acute pancreatitis hospitalizations in the United States SO PANCREAS LA English DT Article DE acute pancreatitis; cost; hospitalization ID MORTALITY; CARE AB Objectives: To determine the direct medical costs of hospitalizations for acute pancreatitis in the United States and analyze the demographic characteristics of hospitalized patients. Methods: We searched the 2003 Healthcare Cost and Utilization Project-National Inpatient Sample for hospitalizations with a primary discharge diagnosis of acute pancreatitis. These were analyzed with respect to patient demographics, hospitalization rates, and total hospital charges and costs. Results: The estimated total cost for acute pancreatitis admissions was $2.2 billion (95% confidence interval [CI], 2.0 billion-2.3 billion) at a mean cost per hospitalization of $9870 (95% CI, 9300-10,400), and a mean cost per hospital day of $1670 (95% CI, 1620-1720). Costs per hospitalization were higher in urban hospitals, teaching hospitals, and for patients older than 65 years, based on a longer length of stay (LOS). The hospitalization rate was 0.52 per 1000 US population (95% CI, 0.48-0.56) for whites versus 0.76 per 1000 (95% CI, 0.65-0.87) for blacks. Conclusions: Acute pancreatitis hospitalizations cost more than $2 billion annually, and certain population groups (blacks and older patients) have disproportionately high hospitalization rates. This study highlights the need for prevention efforts, particularly targeting high-risk groups, and for further studies to identify cost effective treatment strategies for acute pancreatitis. C1 [Harris, N. Stuart; Pelletier, Andrea J.; Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Fagenholz, Peter J.; Castillo, Carlos Fernandez-del] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Camargo, CA (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Suite 410,326 Cambridge St, Boston, MA 02114 USA. EM ccamargo@partners.org NR 18 TC 101 Z9 104 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-3177 J9 PANCREAS JI Pancreas PD NOV PY 2007 VL 35 IS 4 BP 302 EP 307 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 248TS UT WOS:000252179100002 PM 18090234 ER PT J AU Alexander, BM Hezel, AF Del-Castillo, CF Kachnic, LA Niemierko, A Kozak, KR Blaszkowsky, LS Warshaw, AL Willett, CG Ryan, DP Clark, JW Hong, TS AF Alexander, B. M. Hezel, A. F. Del-Castillo, C. Fernandez Kachnic, L. A. Niemierko, A. Kozak, K. R. Blaszkowsky, L. S. Warshaw, A. L. Willett, C. G. Ryan, D. P. Clark, J. W. Hong, T. S. TI Improved outcome of pancreatic adenocarcinoma arising in intraductal papillary mucinous tumors is due to earlier stage at presentation SO PANCREAS LA English DT Meeting Abstract C1 [Alexander, B. M.; Hezel, A. F.; Del-Castillo, C. Fernandez; Kachnic, L. A.; Niemierko, A.; Blaszkowsky, L. S.; Warshaw, A. L.; Ryan, D. P.; Clark, J. W.; Hong, T. S.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA USA. [Willett, C. G.] Duke Univ, Med Ctr, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-3177 J9 PANCREAS JI Pancreas PD NOV PY 2007 VL 35 IS 4 BP 392 EP 392 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 248TS UT WOS:000252179100027 ER PT J AU Alexander, BM Del-Castillo, CF Kachnic, LA Niemierko, A Kozak, KR Blaszkowsky, LS Warshaw, AL Willett, CG Ryan, DP Clark, JW Hong, TS AF Alexander, B. M. Del-Castillo, C. Fernandez Kachnic, L. A. Niemierko, A. Kozak, K. R. Blaszkowsky, L. S. Warshaw, A. L. Willett, C. G. Ryan, D. P. Clark, J. W. Hong, T. S. TI Adjuvant chemoradiation provides benefit for patients with advanced invasive intraductal papillary mucinous neoplasm SO PANCREAS LA English DT Meeting Abstract C1 [Alexander, B. M.; Del-Castillo, C. Fernandez; Kachnic, L. A.; Niemierko, A.; Kozak, K. R.; Blaszkowsky, L. S.; Warshaw, A. L.; Ryan, D. P.; Clark, J. W.; Hong, T. S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Willett, C. G.] Duke Univ, Med Ctr, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-3177 J9 PANCREAS JI Pancreas PD NOV PY 2007 VL 35 IS 4 BP 392 EP 392 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 248TS UT WOS:000252179100026 ER PT J AU Kelly, K Bardeesy, N Anbazhagan, R Gurumurthy, S Berger, J Alencar, H Mahmood, U Weissleder, R AF Kelly, K. Bardeesy, N. Anbazhagan, R. Gurumurthy, S. Berger, J. Alencar, H. Mahmood, U. Weissleder, R. TI Targeted nanoparticles for imaging incipient pancreatic ductal adenocarinoma SO PANCREAS LA English DT Meeting Abstract C1 [Kelly, K.; Anbazhagan, R.; Alencar, H.; Mahmood, U.; Weissleder, R.] Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA USA. [Kelly, K.; Anbazhagan, R.; Alencar, H.; Mahmood, U.; Weissleder, R.] Harvard Univ, Sch Med, Charlestown, MA USA. [Bardeesy, N.; Gurumurthy, S.; Berger, J.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Mahmood, U.; Weissleder, R.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-3177 J9 PANCREAS JI Pancreas PD NOV PY 2007 VL 35 IS 4 BP 408 EP 409 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 248TS UT WOS:000252179100084 ER PT J AU LaFemina, J Stirman, A Alsina, J Mino-Kenudson, M del Castillo, CF Warshaw, AL Thayer, SP AF LaFemina, J. Stirman, A. Alsina, J. Mino-Kenudson, M. Fernandez-del Castillo, C. Warshaw, A. L. Thayer, S. P. TI Paradoxical inhibition of ductal proliferation due to shh misexpression with p16(-/-) is accompanied by pluripotential cell expansion SO PANCREAS LA English DT Meeting Abstract C1 [LaFemina, J.; Stirman, A.; Alsina, J.; Mino-Kenudson, M.; Fernandez-del Castillo, C.; Warshaw, A. L.; Thayer, S. P.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-3177 J9 PANCREAS JI Pancreas PD NOV PY 2007 VL 35 IS 4 BP 409 EP 410 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 248TS UT WOS:000252179100087 ER PT J AU Nikfarjam, M Warshaw, A Axelrod, L Deshpande, V Thayer, S Ferrone, C Fernandez-del Castillo, C AF Nikfarjam, M. Warshaw, A. Axelrod, L. Deshpande, V. Thayer, S. Ferrone, C. Fernandez-del Castillo, C. TI Improved contemporary surgical management of insulinoma: A 25-year experience at the Massachusetts General Hospital SO PANCREAS LA English DT Meeting Abstract C1 [Nikfarjam, M.; Warshaw, A.; Thayer, S.; Ferrone, C.; Fernandez-del Castillo, C.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-3177 J9 PANCREAS JI Pancreas PD NOV PY 2007 VL 35 IS 4 BP 419 EP 420 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 248TS UT WOS:000252179100120 ER PT J AU Odinokova, IV Sung, KF Hermann, K Mareninova, OA Gukovsky, I Gukovskaya, AS AF Odinokova, I. V. Sung, K. F. Hermann, K. Mareninova, O. A. Gukovsky, I. Gukovskaya, A. S. TI Bcl-xL and Bcl-2 prosurvival proteins protect against necrosis in pancreatitis SO PANCREAS LA English DT Meeting Abstract C1 [Odinokova, I. V.; Sung, K. F.; Hermann, K.; Mareninova, O. A.; Gukovsky, I.; Gukovskaya, A. S.] Vet Affairs Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Odinokova, I. V.; Sung, K. F.; Hermann, K.; Mareninova, O. A.; Gukovsky, I.; Gukovskaya, A. S.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-3177 J9 PANCREAS JI Pancreas PD NOV PY 2007 VL 35 IS 4 BP 420 EP 420 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 248TS UT WOS:000252179100121 ER PT J AU Osgood, S Kolodecik, TR Reeve, J Pandol, SJ Gorelick, FS Thrower, EC AF Osgood, S. Kolodecik, T. R. Reeve, J. Pandol, S. J. Gorelick, F. S. Thrower, E. C. TI Differential roles of protein kinase C isoforms in acute pancreatitis SO PANCREAS LA English DT Meeting Abstract C1 [Osgood, S.; Kolodecik, T. R.; Gorelick, F. S.; Thrower, E. C.] Vet Adm Connecticut Healthcare, Dept Internal Med, Sect Digest Dis, West Haven, CT USA. [Gorelick, F. S.] Vet Adm Connecticut Healthcare, Dept Cell Biol, West Haven, CT USA. [Gorelick, F. S.] Yale Univ, Sch Med, New Haven, CT USA. [Reeve, J.; Pandol, S. J.] VA Greater Los Angeles Hlth Care Syst, Los Angeles, CA USA. [Reeve, J.; Pandol, S. J.] Univ Calif Los Angeles, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-3177 J9 PANCREAS JI Pancreas PD NOV PY 2007 VL 35 IS 4 BP 420 EP 420 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 248TS UT WOS:000252179100123 ER PT J AU Strobel, O Dor, Y Alsina, J Stirman, A Lauwers, G Trainor, A Fernandez-del Castillo, C Warshaw, A Thayer, S AF Strobel, O. Dor, Y. Alsina, J. Stirman, A. Lauwers, G. Trainor, A. Fernandez-del Castillo, C. Warshaw, A. Thayer, S. TI In vivo lineage tracing defines the role of acinar-to-ductal transdifferentiation in inflammation-mediated ductal metaplasia SO PANCREAS LA English DT Meeting Abstract C1 [Strobel, O.; Alsina, J.; Stirman, A.; Trainor, A.; Fernandez-del Castillo, C.; Warshaw, A.; Thayer, S.] Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Strobel, O.; Alsina, J.; Stirman, A.; Trainor, A.; Fernandez-del Castillo, C.; Warshaw, A.; Thayer, S.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Lauwers, G.] Harvard Univ, Sch Med, Boston, MA USA. [Dor, Y.] Hebrew Univ Jerusalem, Hadassah Med Sch, IL-91010 Jerusalem, Israel. [Strobel, O.] Univ Heidelberg, Dept Gen Surg, Heidelberg, Germany. RI Dor, Yuval/C-2405-2011 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 0885-3177 J9 PANCREAS JI Pancreas PD NOV PY 2007 VL 35 IS 4 BP 429 EP 429 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 248TS UT WOS:000252179100153 ER PT J AU Zhao, G Reyes, CN Hermann, K Sung, KF Gukovskaya, AS Hoffmann, A Pandol, SJ Gukovsky, I AF Zhao, G. Reyes, C. N. Hermann, K. Sung, K. F. Gukovskaya, A. S. Hoffmann, A. Pandol, S. J. Gukovsky, I. TI Genetic deletions of NF-kappa B proteins ameliorate cerulein-induced pancreatitis SO PANCREAS LA English DT Meeting Abstract C1 [Zhao, G.; Reyes, C. N.; Hermann, K.; Sung, K. F.; Gukovskaya, A. S.; Pandol, S. J.; Gukovsky, I.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Zhao, G.; Reyes, C. N.; Hermann, K.; Sung, K. F.; Gukovskaya, A. S.; Pandol, S. J.; Gukovsky, I.] Univ Calif Los Angeles, Los Angeles, CA USA. [Zhao, G.] Beijing Hosp, Beijing, Peoples R China. [Sung, K. F.] Chang Gung Mem Hosp, Taipei 10591, Taiwan. [Hoffmann, A.] Univ Calif San Diego, La Jolla, CA 92093 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-3177 J9 PANCREAS JI Pancreas PD NOV PY 2007 VL 35 IS 4 BP 438 EP 438 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 248TS UT WOS:000252179100184 ER PT J AU Lambert-Messerlian, G Eklund, E Pinar, H Tantravahi, U Schneyer, AL AF Lambert-Messerlian, Geralyn Eklund, Elizabeth Pinar, Halit Tantravahi, Uiviadevi Schneyer, Andalan L. TI Activin subunit and receptor expression in normal and human fetal cleft palate tissues SO PEDIATRIC AND DEVELOPMENTAL PATHOLOGY LA English DT Article DE activin; cleft; palate ID MESSENGER RIBONUCLEIC-ACIDS; LIVING HUMAN FETUSES; BETA-A SUBUNITS; MOLECULAR CHARACTERISTICS; RAT EMBRYOGENESIS; MICE DEFICIENT; FOLLISTATIN; INHIBIN; BONE; LOCALIZATION AB Craniofacial malformations, such as cleft palate, present serious complications in the newborn and are often of unknown etiology. Activin B-A subunit deletion leads to cleft palate in mice, but the expression of this protein in the human palate has not been explored. Our goal was to determine the spatial and temporal expression of inhibin/ activin subunits; the binding protein, follistatin; and activin receptors in the human fetal palate. Residual human fetal palate tissues, with or without cleft, were collected during routine autopsy at Women and Infants Hospital. Inhibin/activin alpha and beta subunits, follistatin, and activin receptor protein and mRNA expression were studied by inu-nunocytochemistry and reverse-transcriptase polymerase chain reaction (RT-PCR) experiments, respectively. Dimeric activin A levels were compared in cleft and normal palate tissue homogenates by immunoassay. Activin BA, follistatin, and activin receptor type IIA proteins were observed in normal and cleft palate tissues throughout pregnancy (gestational weeks 11 to 40). Proteins were predominantly found in developing bone cells, with no significant group differences. Inhibin/activin B-A subunit, follistatin, and activin receptor mRNAs were also detected in normal and cleft fetal palate tissues, but inhibin alpha and B-B subunit were absent. Inhibin/activin B-A subunit expression was consistent with the presence of dimeric activin A, but levels did not differ significantly between cleft and control tissues. Inhibin/activin B-A subunit, follistatin, and activin receptor proteins and mRNAs are present in the human fetal palate. These data suggest that activin signalling has the potential to be associated with human palate development. C1 Brown Univ, Women & Infants Hosp, Dept Pathol & Lab Med, Providence, RI 02912 USA. Brown Univ, Warren Alpert Med Sch, Providence, RI 02912 USA. Brown Univ, Women & Infants Hosp, Dept Pediat, Providence, RI 02908 USA. Massachusetts Gen Hosp, Reprod Endocrine Unit, Boston, MA 02114 USA. RP Lambert-Messerlian, G (reprint author), Brown Univ, Women & Infants Hosp, Dept Pathol & Lab Med, Providence, RI 02912 USA. EM gmesserl@wihri.org NR 37 TC 2 Z9 2 U1 0 U2 0 PU ALLIANCE COMMUNICATIONS GROUP DIVISION ALLEN PRESS PI LAWRENCE PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 USA SN 1093-5266 J9 PEDIATR DEVEL PATHOL JI Pediatr. Dev. Pathol. PD NOV-DEC PY 2007 VL 10 IS 6 BP 436 EP 445 DI 10.2350/06-05-0087.1 PG 10 WC Pathology; Pediatrics SC Pathology; Pediatrics GA 232RB UT WOS:000251035800002 PM 18001154 ER PT J AU Eichler, F Krishnamoorthy, K Grant, PE AF Eichler, Florian Krishnamoorthy, Kalpathy Grant, P. Ellen TI Magnetic resonance Imaging evaluation of possible neonatal sinovenous thrombosis SO PEDIATRIC NEUROLOGY LA English DT Article ID CEREBRAL VENOUS THROMBOSIS; SINUS THROMBOSIS; INTRAVENTRICULAR HEMORRHAGE; MR VENOGRAPHY; CHILDREN; ANATOMY AB There are few data on magnetic resonance imaging findings in newborns for whom there is a concern for cerebral sinovenous thrombosis. The study objective was to document findings on magnetic resonance imaging or magnetic resonance venography in cases of suspected neonatal sinovenous thrombosis. A retrospective search of the institutional database was performed to find neonates whose cranial computed tomography raised the suspicion for thrombus. Documented abnormalities were detected on magnetic resonance venography, diffusion-weighted imaging, and T-2-weigbted imaging. Of 15 neonates with suspicious computed tomography studies, 2 had a definite intraluminal clot in the deep venous system; the remainder showed decreased flow-related enhancement within the dural venous sinuses. In all these cases, the sinus was compressed by adjacent subdural hematoma or sutural diastasis. Of the 15 patients, 5 had parenchymal abnormalities (2 of these had definite intraluminal clot). Parenchymal abnormalities were classified as hemorrhage (3/5), cytotoxic edema (3/5), or vasogenic edema (1/5). Intraluminal clot in the newborn is more often identified in the deep than in the superficial venous system. With evidence of venous injury in the absence of identified thrombus, it is possible that either clots dissolve quickly, escaping detection, or that the superficial venous system is vulnerable to mechanical forces during delivery. (C) 2007 by Elsevier Inc. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Neurol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Martinos Ctr Biomed Imaging, Boston, MA USA. RP Grant, PE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol, 55 Fruit St, Boston, MA 02114 USA. EM pegrant@partners.org FU NINDS NIH HHS [1K08NS52550-01A1] NR 18 TC 20 Z9 20 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0887-8994 J9 PEDIATR NEUROL JI Pediatr. Neurol. PD NOV PY 2007 VL 37 IS 5 BP 317 EP 323 DI 10.1016/j.pediatrneurol.2007.06.018 PG 7 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 226VH UT WOS:000250616100002 PM 17950416 ER PT J AU Weng, M Walker, WA Sanderson, IR AF Weng, Meiqian Walker, W. Allan Sanderson, Ian R. TI Butyrate regulates the expression of pathogen-triggered IL-8 in intestinal epithelia SO PEDIATRIC RESEARCH LA English DT Article ID KAPPA-B; CACO-2 CELLS; SECRETION; NEUTROPHIL; ACTIVATION; INDUCTION; INFECTION; CHEMOKINE; PROTEIN AB Inflammatory bowel disease (IBD) is characterized by an exaggerated immune response that involves pro-inflammatory cytokines including IL-8. Production of these pro-inflammatory cytokines is triggered by pathogen-associated molecular patterns (PAMP). Butyrate, a product of bacterial fermentation of carbohydrates, has been reported to modulate inflammation in IBD, possibly by regulating production of pro-inflammatory cytokines. However, this effect of butyrate is controversial. In this study, we used Pam3CSK4 (Pam3CysSerLys4), the acylated NH2-terminus of the bacterial lipoprotein (a PAMP), to mimic in vivo infection of pathogens. Butyrate transiently down-regulated expression of IL-8 stimulated by Pam3CSK4. Treatment of cells with butyrate before Pam3CSK4, however, enhanced production of IL-8. Furthermore, butyrate induced expression of A20, a negative regulator of the nuclear factor-kappa B pathway. Over-expression of A20 inhibited Pam3CSK4-triggered IL-8 expression. Our data suggest that the inflammatory modulation of butyrate in IBD is mediated by A20 and a short pulse rather than continuous administration of butyrate may provide a protective effect on IBD. C1 Massachusetts Gen Hosp, Dept Pediat, Div Pediat Gastroenterol & Nutr, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Barts & London Queen Marys Sch Med & Dent, Barts & London, Res Ctr Gastroenterol, London E1 2AT, England. RP Walker, WA (reprint author), MA Gen Hosp Children, Div Pediat Gastroenterol & Nutr, Dept Pediat, Dev Gastroenterol Lab, 114 16th St 1143503, Charlestown, MA 02129 USA. EM wwalker@partners.org FU NIDDK NIH HHS [P30 DK040561-12, P01 DK033506, P30 DK040561] NR 21 TC 21 Z9 22 U1 0 U2 6 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 W CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD NOV PY 2007 VL 62 IS 5 BP 542 EP 546 PG 5 WC Pediatrics SC Pediatrics GA 224WD UT WOS:000250477000005 PM 17805211 ER PT J AU Arnold, LE Lindsay, RL Lopez, FA Jacob, SE Biederman, J Findling, RL Ramadan, Y AF Arnold, L. Eugene Lindsay, Ronald L. Lopez, Frank A. Jacob, Sharon E. Biederman, Joseph Findling, Robert L. Ramadan, Yaser TI Treating attention-deficit/hyperactivity disorder with a stimulant Transdermal patch: The clinical art SO PEDIATRICS LA English DT Article DE attention-deficit/hyperactivity disorder; methylphenidate; transdermal system ID CHILDREN; BEHAVIOR AB Stimulant medications ( amphetamine and methylphenidate) are the best-documented treatments for attention-deficit/hyperactivity disorder, but their short pharmacokinetic and behavioral half-lives have historically produced irksome time-course effects. New drug-delivery systems designed to eliminate the need for frequent dosing include the methylphenidate transdermal system, in which the matrix acts as both the drug reservoir and the skin adhesive. The methylphenidate transdermal system patch, in contrast to long-acting oral preparations, requires a paradigmatic shift in clinical thinking, as well as refinement of clinical management skills. For dosing with the methylphenidate transdermal system patch, clinicians must think in terms of a retrievable form of drug delivery ( in milligrams per hour) rather than a fixed nonretrievable dose ( in milligrams per dose or milligrams per day). Clinicians and patients can determine the optimal clinical dose by controlling 2 variables: ( 1) patch size ( controlling milligrams per hour) and ( 2) duration of patch wear. The new paradigm is worth learning, because the patch offers several advantages over oral preparations for some patients, chiefly individualized control over effect duration ( determined by when the patch is applied in the morning and removed in the afternoon/evening). Taking full advantage of this treatment option requires educating the patient and parents regarding practical elements of daily use. These elements include patch-site selection, application techniques, management of wear time to optimize the daily time course of clinical benefits, and skin hygiene. This article summarizes clinical principles that physicians may find useful in managing this new addition to the attention-deficit/hyperactivity disorder treatment armamentarium. C1 Ohio State Univ, Dept Psychiat, Columbus, OH 43210 USA. St Josephs Hosp, Arizona Child Study Ctr, Phoenix, AZ USA. Childrens Dev Ctr, Maitland, FL USA. Univ Miami, Dept Dermatol & Cutaneous Surg, Miami, FL USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Psychopharmacol Dept, Boston, MA USA. Case Western Reserve Univ, Dept Psychiat & Pediat, Cleveland, OH 44106 USA. RP Arnold, LE (reprint author), Ohio State Univ, Dept Psychiat, 479 Galena Rd, Sunbury, OH 43074 USA. EM arnold.6@osu.edu NR 19 TC 14 Z9 14 U1 3 U2 6 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD NOV PY 2007 VL 120 IS 5 BP 1100 EP 1106 DI 10.1542/peds.2007-0542 PG 7 WC Pediatrics SC Pediatrics GA 226WJ UT WOS:000250618900021 PM 17974748 ER PT J AU Major, P Thiele, EA AF Major, Philippe Thiele, Elizabeth A. TI Seizures in children: Laboratory diagnosis and management SO PEDIATRICS IN REVIEW LA English DT Review ID QUALITY STANDARDS SUBCOMMITTEE; PRACTICE PARAMETER; NEUROLOGY SOCIETY; AMERICAN ACADEMY C1 [Major, Philippe; Thiele, Elizabeth A.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Major, P (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. NR 8 TC 4 Z9 4 U1 0 U2 1 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0191-9601 J9 PEDIATR REV JI Pediatr. Rev. PD NOV PY 2007 VL 28 IS 11 BP 405 EP 414 DI 10.1542/pir.28-11-405 PG 10 WC Pediatrics SC Pediatrics GA 239RL UT WOS:000251535300002 PM 17974703 ER PT J AU Xiao, FM He, P Abramovitch, RB Dawson, JE Nicholson, LK Sheen, J Martin, GB AF Xiao, Fangming He, Ping Abramovitch, Robert B. Dawson, Jennifer E. Nicholson, Linda K. Sheen, Jen Martin, Gregory B. TI The N-terminal region of Pseudomonas type III effector AvrPtoB elicits Pto-dependent immunity and has two distinct virulence determinants SO PLANT JOURNAL LA English DT Article DE immunity; Pto kinase; programmed cell death; guard hypothesis; type III effectors; structural biology ID PROGRAMMED CELL-DEATH; SYRINGAE PV. TOMATO; PLANT-DISEASE-RESISTANCE; E3 UBIQUITIN LIGASE; AVIRULENCE PROTEIN AVRPTO; BACTERIAL SPECK DISEASE; SECRETION SYSTEM; HYPERSENSITIVE RESPONSE; INNATE IMMUNITY; RECOGNITION SPECIFICITY AB Resistance to bacterial speck disease in tomato is activated by the physical interaction of the host Pto kinase with either of the sequence-dissimilar type III effector proteins AvrPto or AvrPtoB (HopAB2) from Pseudomonas syringae pv. tomato. Pto-mediated immunity requires Prf, a protein with a nucleotide-binding site and leucine-rich repeats. The N-terminal 307 amino acids of AvrPtoB were previously reported to interact with the Pto kinase, and we show here that this region (AvrPtoB(1-307)) is sufficient for eliciting Pto/Prf-dependent immunity against P. s. pv. tomato. AvrPtoB(1-307) was also found to be sufficient for a virulence activity that enhances ethylene production and increases growth of P. s. pv. tomato and severity of speck disease on susceptible tomato lines lacking either Pto or Prf. Moreover, we found that residues 308-387 of AvrPtoB are required for the previously reported ability of AvrPtoB to suppress pathogen-associated molecular patterns-induced basal defenses in Arabidopsis. Thus, the N-terminal region of AvrPtoB has two structurally distinct domains involved in different virulence-promoting mechanisms. Random and targeted mutagenesis identified five tightly clustered residues in AvrPtoB(1-307) that are required for interaction with Pto and for elicitation of immunity to P. s. pv. tomato. Mutation of one of the five clustered residues abolished the ethylene-associated virulence activity of AvrPtoB(1-307). However, individual mutations of the other four residues, despite abolishing interaction with Pto and avirulence activity, had no effect on AvrPtoB(1-307) virulence activity. None of these mutations affected the basal defense-suppressing activity of AvrPtoB(1-387). Based on sequence alignments, estimates of helical propensity, and the previously reported structure of AvrPto, we hypothesize that the Pto-interacting domains of AvrPto and AvrPtoB(1-307) have structural similarity. Together, these data support a model in which AvrPtoB(1-307) promotes ethylene-associated virulence by interaction not with Pto but with another unknown host protein. C1 Cornell Univ, Boyce Thompson Inst Plant Res, Ithaca, NY 14853 USA. Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. Cornell Univ, Dept Plant Pathol, Ithaca, NY 14853 USA. Cornell Univ, Dept Mol Biol & Genet, Ithaca, NY 14853 USA. RP Martin, GB (reprint author), Cornell Univ, Boyce Thompson Inst Plant Res, Tower Rd, Ithaca, NY 14853 USA. EM gbm7@cornell.edu RI Martin, Gregory/F-6262-2011; Abramovitch, Robert/A-5324-2013; OI Martin, Gregory/0000-0003-0044-6830; Abramovitch, Robert/0000-0002-4119-4169 FU NIGMS NIH HHS [R01 GM078021, R01 GM078021-02, R01-GM078021] NR 69 TC 48 Z9 49 U1 1 U2 8 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0960-7412 J9 PLANT J JI Plant J. PD NOV PY 2007 VL 52 IS 4 BP 595 EP 614 DI 10.1111/j.1365-313X.2007.03259.x PG 20 WC Plant Sciences SC Plant Sciences GA 228LE UT WOS:000250730600001 PM 17764515 ER PT J AU Deo, RC Patterson, N Tandon, A McDonald, GJ Haiman, CA Ardlie, K Henderson, BE Henderson, SO Reich, D AF Deo, Rahul C. Patterson, Nick Tandon, Arti McDonald, Gavin J. Haiman, Christopher A. Ardlie, Kristin Henderson, Brian E. Henderson, Sean O. Reich, David TI A high-density admixture scan in 1,670 African Americans with hypertension SO PLOS GENETICS LA English DT Article ID BLOOD-PRESSURE; GENOME SCANS; DISEASE GENES; METAANALYSIS; ASSOCIATION; SAMPLES; ADULTS; LOCUS AB Hypertension (HTN) is a devastating disease with a higher incidence in African Americans than European Americans, inspiring searches for genetic variants that contribute to this difference. We report the results of a large-scale admixture scan for genes contributing HTN risk, in which we screened 1,670 African Americans with HTN and 387 control individuals for regions of the genome with elevated proportion of African or European ancestry. No loci were identified that were significantly associated with HTN. We also searched for evidence of an admixture signal at 40 candidate genes and eight previously reported linkage peaks, but none appears to contribute substantially to the differential HTN risk between African and European Americans. Finally, we observed nominal association at one of the loci detected in the admixture scan of Zhu et al. 2005 (p = 0.016 at 6q24.3 correcting for four hypotheses tested), although we caution that the significance is marginal and the estimated odds ratio of 1.19 per African allele is less than what would be expected from the original report; thus, further work is needed to follow up this locus. C1 Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Div Cardiol, Boston, MA USA. Harvard & MIT, Program Med & Populat Genet, Boston, MA USA. Univ So Calif, Dept Prevent Med, Keck Sch Med, Los Angeles, CA 90089 USA. Genom Collaborat, Cambridge, MA USA. Univ So Calif, Dept Emergency Med, Keck Sch Med, Los Angeles, CA USA. RP Deo, RC (reprint author), Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. EM rdeo@partners.org; reich@genetics.med.harvard.edu FU NCI NIH HHS [CA63464, R01 CA063464, U01 CA063464]; NHGRI NIH HHS [HG004168, U01 HG004168]; NHLBI NIH HHS [HL084107, R01 HL084107] NR 32 TC 37 Z9 37 U1 0 U2 0 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7390 J9 PLOS GENET JI PLoS Genet. PD NOV PY 2007 VL 3 IS 11 BP 2200 EP 2207 AR e196 DI 10.1371/journal.pgen.0030196 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 236NR UT WOS:000251310200014 PM 18020707 ER PT J AU Szulc, ZM Obeid, LM Hannun, YA Bielawska, A AF Szulc, Z. M. Obeid, L. M. Hannun, Y. A. Bielawska, A. TI Highly efficient and regioselective phosphorylation of sphingolipids by phase-transfer catalysis SO POLISH JOURNAL OF CHEMISTRY LA English DT Article DE phosphorylation; trimethyl phosphite; 1,2-dibromotetrachloroethane; phase-transfer catalysis; sphingosine; ceramide; sphingosine 1-phosphate; ceramide 1-phosphate ID SPHINGOSINE 1-PHOSPHATE; CERAMIDE 1-PHOSPHATE; SPHINGOSINE-1-PHOSPHATE; ANALOGS; TRIPHENYLPHOSPHINE; SPHINGOMYELIN; NUCLEOPHILES; PHOSPHONATE; ACTIVATION; PROTECTION AB Phosphorylation of D-erythro-sphingosine and its N-BOC or N-palmitoyl derivatives with trimethyl phosphite was carried out in 72-92% yield at room temperature for 20 min in a biphasic system comprised of dichloromethane/aqueous solutions of NaOH or K(2)CO(3) using 1,2-dibromotetrachloroethane as a source of halogen and cetyl pyridinium bromide as a phase-transfer catalyst. These are the first reported examples of a highly selective 0- and N-phosphorylation of sphingolipids by the phase-transfer catalysis. Our studies show that the developed phosphorylation protocol works as a modular process, in which the synthetic outcome is controlled by a type of the used base, catalyst and solvent system. C1 [Szulc, Z. M.; Hannun, Y. A.; Bielawska, A.] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. [Obeid, L. M.] Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. [Obeid, L. M.] Med Univ S Carolina, Ralph H Johnson Vet Adm Med Ctr, Charleston, SC 29425 USA. RP Szulc, ZM (reprint author), Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29425 USA. EM szulcz@musc.edu OI obeid, lina/0000-0002-0734-0847 NR 57 TC 2 Z9 2 U1 0 U2 3 PU POLISH CHEMICAL SOC PI WARSAW PA C/O POLISH ACAD SCIENCES, INST PHYSICAL CHEMISTRY, UL KASPRZAKA 44/52, 01-224 WARSAW, POLAND SN 0137-5083 J9 POL J CHEM JI Pol. J. Chem. PD NOV PY 2007 VL 81 IS 11 BP 1899 EP 1909 PG 11 WC Chemistry, Multidisciplinary SC Chemistry GA 243HI UT WOS:000251787000007 ER PT J AU Palmer, RC Emmons, KM Fletcher, RH Lobb, R Miroshnik, I Kemp, JA Bauer, M AF Palmer, Richard C. Emmons, Karen M. Fletcher, Robert H. Lobb, Rebecca Miroshnik, Irina Kemp, James Alan Bauer, Mark TI Familial risk and colorectal cancer screening health beliefs and attitudes in an insured population SO PREVENTIVE MEDICINE LA English DT Article DE colon cancer; cancer screening; health beliefs; family history ID 1ST-DEGREE RELATIVES; INDIVIDUALS; KNOWLEDGE; HISTORY; PARTICIPATION; ADHERENCE; PATTERNS; BEHAVIOR; BARRIERS; ADOPTION AB Objective. To examine the relationship between health beliefs and attitudes toward colorectal cancer screening, strength of family history risk, and being appropriately screened for colorectal cancer. Methods. In February 2004, 7000 randomly selected members of a multi-specialty group practice located in Boston, MA were mailed a brief survey that was used to ascertain colorectal cancer family history. A follow-up survey that contained questions representing selected constructs of the Health Belief Model, Theory of Planned Behavior, and healthcare experiences was then mailed to all 355 individuals who reported a family history in the initial survey and 710 randomly selected participants with no colorectal cancer family history. Results. Participants who were appropriately screened had higher mean scores for perceived cancer risk, subjective norms, and perceived benefits and lower scores for perceived barriers. Multivariate findings indicate that having high perceptions of risk for colorectal cancer was a significant correlate of being screened appropriately among individuals with a strong family history. Conclusions. For those at greatest colorectal cancer risk due to family history, ensuring that these individuals understand their personal risk might lead to increased colorectal cancer screening participation. Future intervention research is warranted to examine if raising perceptions of risk can increase screening behaviors in individuals with colorectal cancer risk due to family history. (c) 2007 Elsevier Inc. All rights reserved. C1 [Palmer, Richard C.; Emmons, Karen M.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Palmer, Richard C.; Emmons, Karen M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Fletcher, Robert H.; Lobb, Rebecca; Miroshnik, Irina] Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA 02115 USA. [Fletcher, Robert H.; Lobb, Rebecca; Miroshnik, Irina] Harvard Pilgrim Hlth Care, Boston, MA 02115 USA. [Kemp, James Alan; Bauer, Mark] Harvard Vanguard Med Associates, Newton, MA 02446 USA. RP Palmer, RC (reprint author), Florida Int Univ, Stempel Sch Publ Hlth, 11200 SW 8th St, Miami, FL 33199 USA. EM richard.palmer@fiu.edu OI Lobb, Rebecca/0000-0003-3503-0675 FU NCI NIH HHS [1 R21 CA102381-01] NR 33 TC 33 Z9 34 U1 2 U2 8 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 J9 PREV MED JI Prev. Med. PD NOV PY 2007 VL 45 IS 5 BP 336 EP 341 DI 10.1016/j.ypmed.2007.07.021 PG 6 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 240BW UT WOS:000251563000006 PM 17804048 ER PT J AU Kazantsev, AG Hersch, SM AF Kazantsev, Aleksey G. Hersch, Steven M. TI Drug targeting of dysregulated transcription in Huntington's disease SO PROGRESS IN NEUROBIOLOGY LA English DT Review DE Huntington's disease; transcriptional dysregulation; mutant huntingtin; transcription factor(s); small molecule; neuroprotection ID NEURONAL INTRANUCLEAR INCLUSIONS; HISTONE DEACETYLASE INHIBITOR; TRANSGENIC MOUSE MODELS; GENE-EXPRESSION CHANGES; KAPPA-B CONTRIBUTES; MUTANT HUNTINGTIN; LIFE-SPAN; SACCHAROMYCES-CEREVISIAE; REPRESSES TRANSCRIPTION; CAENORHABDITIS-ELEGANS AB Transcriptional dysregulation in Huntington's disease (HD) is a well documented and broadly studied phenomenon. Its basis appears to be in huntingtin's aberrant protein-protein interactions with a variety of transcription factors. The development of therapeutics targeting altered transcription, however, faces serious challenges. No single transcriptional regulator has emerged as a primary actor in HD. The levels of literally hundreds of RNA transcripts are altered in affected cells and it is uncertain which are most relevant. The protein-protein interactions of mutant huntingtin with transcriptional factors do not constitute conventional and easy targets for drug molecules. Nevertheless, potential therapeutic advances, targeting transcriptional deregulation in HD, have been made in recent years. In this chapter we review current progress in this area of therapeutic development. We also discuss possible drug discovery strategies targeting altered transcriptional pathways. (C) 2007 Elsevier Ltd. All rights reserved. C1 Harvard Univ, Massachusetts Gen Hosp, Harvard Med Sch, MassGen Inst Neurodegenerat Dis, Charlestown, MA 02129 USA. RP Kazantsev, AG (reprint author), Harvard Univ, Massachusetts Gen Hosp, Harvard Med Sch, MassGen Inst Neurodegenerat Dis, Bldg 114,16th St, Charlestown, MA 02129 USA. EM akazantsev@partners.org FU NCCIH NIH HHS [R01 AT000613, U01 AT000613-06A1, U01 AT000613, AT00613]; NINDS NIH HHS [P01 NS045242, P01 NS045242-05, R01 NS035255-06, NS045242, NS35255] NR 62 TC 18 Z9 18 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0301-0082 J9 PROG NEUROBIOL JI Prog. Neurobiol. PD NOV PY 2007 VL 83 IS 4 BP 249 EP 259 DI 10.1016/j.pneurobio.2007.02.005 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 233PJ UT WOS:000251102500005 PM 17379386 ER PT J AU Kang, JX AF Kang, Jing X. TI Fat-1 transgenic mice: A new model for omega-3 research SO PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS LA English DT Article; Proceedings Paper CT 8th Workshop on Fatty Acids and Cell Signaling CY 2007 CL Quebec City, CANADA ID N-3 FATTY-ACIDS; MAMMARY-GLAND; OMEGA-3-FATTY-ACIDS; DESATURASE; COLITIS; RICH AB An appropriate animal model that can eliminate confounding factors of diet would be very helpful for evaluation of the health effects of nutrients such as n-3 fatty acids. We recently generated a fat-1 transgenic mouse expressing the Caenorhabditis elegans fat-1 gene encoding an n-3 fatty acid desaturase that converts n-6 to n-3 fatty acids (which is absent in mammals). The fat-1 transgenic mice are capable of producing n-3 fatty acids from the n-6 type, leading to abundant n-3 fatty acids with reduced levels of n-6 fatty acids in their organs and tissues, without the need of a dietary n-3 supply. Feeding an identical diet (high in n-6) to the transgenic and wild-type littermates can produce different fatty acid profiles in these animals. Thus, this model allows well-controlled studies to be performed, without the interference of the potential confounding factors of diet. The transgenic mice are now being used widely and are emerging as a new tool for studying the benefits of n-3 fatty acids and the molecular mechanisms of their action. (C) 2007 Elsevier Ltd. All rights reserved. C1 [Kang, Jing X.] Massachusetts Gen Hosp, Dept Med, Charlestown, MA 02129 USA. [Kang, Jing X.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Kang, JX (reprint author), Massachusetts Gen Hosp, Dept Med, 149-13th St,Room 4433, Charlestown, MA 02129 USA. EM kang.jing@mgh.harvard.edu FU NCI NIH HHS [R01 CA113605, R01 CA113605-02, R01CA-11365] NR 13 TC 77 Z9 84 U1 2 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0952-3278 J9 PROSTAG LEUKOTR ESS JI Prostaglandins Leukot. Essent. Fatty Acids PD NOV-DEC PY 2007 VL 77 IS 5-6 BP 263 EP 267 DI 10.1016/j.plefa.2007.10.010 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism GA 257ZT UT WOS:000252838900007 PM 18042365 ER PT J AU Al-Turkmani, MR Freedman, SD Laposata, M AF Al-Turkmani, M. Rabie Freedman, Steven D. Laposata, Michael TI Fatty acid alterations and n-3 fatty acid supplementation in cystic fibrosis SO PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS LA English DT Article; Proceedings Paper CT 8th Workshop on Fatty Acids and Cell Signaling CY 2007 CL Quebec City, CANADA ID TRANSMEMBRANE CONDUCTANCE REGULATOR; DOCOSAHEXAENOIC ACID; ARACHIDONIC-ACID; EPITHELIAL-CELLS; EICOSAPENTAENOIC ACID; PANCREATIC INSUFFICIENCY; PLATELET ACTIVATION; PULMONARY-FUNCTION; LEUKOTRIENE B-4; OMEGA-3-FATTY-ACIDS AB Specific fatty acid alterations have been described in the blood and tissues of cystic fibrosis (CF) patients. The two most consistent alterations include decreased levels of linoleic acid (LA) and decreased levels of docosahexaenoic acid (DHA). Increased arachidonic acid (AA) release from membrane phospholipids, as well as changes in levels of AA and other monounsaturated and polyunsaturated fatty acids (PUFAs) have also been described in CF. Although mechanisms of fatty acid alterations have not yet been determined, these alterations may have an important role in the progression of the CF disease. There have been several clinical trials in which CF patients were supplemented with n-3 fatty acids. Most trials resulted in an increase in the levels of the supplemental fatty acids in the blood of CF patients in the absence of significant clinical improvement. It is recommended that future trials include a larger population of CF patients and measure multiple clinical outcomes. (C) 2007 Elsevier Ltd. All rights reserved. C1 [Al-Turkmani, M. Rabie; Laposata, Michael] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Freedman, Steven D.] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Dept Med, Cambridge, MA 02138 USA. RP Laposata, M (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, GRB 235,55 Fruit St, Boston, MA 02114 USA. EM mlaposata@partners.org NR 71 TC 27 Z9 27 U1 0 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0952-3278 J9 PROSTAG LEUKOTR ESS JI Prostaglandins Leukot. Essent. Fatty Acids PD NOV-DEC PY 2007 VL 77 IS 5-6 BP 309 EP 318 DI 10.1016/j.plefa.2007.10.009 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism GA 257ZT UT WOS:000252838900013 PM 18036797 ER PT J AU Goodfriend, TL Pedersen, TL Grekin, RJ Hammock, BD Ball, DL Vollmer, A AF Goodfriend, T. L. Pedersen, T. L. Grekin, R. J. Hammock, B. D. Ball, D. L. Vollmer, A. TI Heparin, lipoproteins, and oxygenated fatty acids in blood: A cautionary note SO PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS LA English DT Article; Proceedings Paper CT 8th Workshop on Fatty Acids and Cell Signaling CY 2007 CL Quebec City, CANADA ID LOW-DENSITY-LIPOPROTEIN; LINOLEIC-ACID; LIPID-PEROXIDATION; STRONG INCREASE; QUANTIFICATION; LIPOLYSIS; DISEASES; PLASMA AB We measured 16 nonesterified oxygenated fatty acid derivatives (oxylipids) in plasmas from seven human subjects. Two arterial samples from each subject were analyzed, drawn approximately 2 h apart. We observed a marked increase in levels of most oxylipids in the second sample, as high as 470-fold. Between the first and second samples, subjects received approximately 800-1000 IU of heparin to prevent clotting in intravascular catheters. We postulate that heparin activated lipoprotein lipases, which, in turn, released oxylipids from triglycerides and phospholipids in plasma lipoproteins. Some of that lipolysis may have occurred during sample storage. Measurements of nonesterified lipids in human plasma may be distorted if heparin is administered to subjects before blood is drawn and if lipase inhibitors are omitted from stored samples. Published by Elsevier Ltd. C1 [Goodfriend, T. L.; Ball, D. L.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI 53705 USA. [Goodfriend, T. L.; Ball, D. L.] Univ Wisconsin, Madison, WI 53705 USA. [Grekin, R. J.; Vollmer, A.] Univ Michigan, Ann Arbor, MI 48109 USA. [Pedersen, T. L.; Hammock, B. D.] Univ Calif Davis, Dept Entomol, Davis, CA 95616 USA. RP Goodfriend, TL (reprint author), William S Middleton Mem Vet Adm Med Ctr, 2500 Overlook Terrace, Madison, WI 53705 USA. EM theodre.goodfriend@med.va.gov FU NHLBI NIH HHS [R01 HL076238-01A1]; NIEHS NIH HHS [P42 ES004699, R37 ES02710] NR 14 TC 11 Z9 11 U1 0 U2 3 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0952-3278 J9 PROSTAG LEUKOTR ESS JI Prostaglandins Leukot. Essent. Fatty Acids PD NOV-DEC PY 2007 VL 77 IS 5-6 BP 363 EP 366 DI 10.1016/j.plefa.2007.10.012 PG 4 WC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism GA 257ZT UT WOS:000252838900019 PM 18036802 ER PT J AU Chen, LB Hartman, S Zetter, B Zhang, S AF Chen, Lan-Bo Hartman, Stan Zetter, Bruce Zhang, Shuguang TI John M. Buchanan (1917-2007) - In memoriam SO PROTEIN SCIENCE LA English DT Biographical-Item C1 Harvard Univ, Sch Med, Dept Gen Surg, Cambridge, MA 02138 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Boston Univ, Boston, MA 02215 USA. MIT, Ctr Biomed Engn, Cambridge, MA 02139 USA. RP Chen, LB (reprint author), Harvard Univ, Sch Med, Dept Gen Surg, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD NOV PY 2007 VL 16 IS 11 BP 2578 EP 2579 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 224JX UT WOS:000250444400026 ER PT J AU Van Citters, AD Naidoo, U Foti, ME AF Van Citters, Aricca D. Naidoo, Umadevi Foti, Mary Ellen TI Using a hypothetical scenario to inform psychiatric advance directives SO PSYCHIATRIC SERVICES LA English DT Article ID SERIOUS MENTAL-ILLNESS; ELECTROCONVULSIVE-THERAPY; ATTITUDES; HOSPITALIZATION; PROVIDER; USERS AB Objectives: The study addressed whether a hypothetical psychiatric scenario is a feasible approach for eliciting psychiatric treatment preferences and identified consumer preferences regarding involuntary care. Methods: Community-residing adults with serious mental illness (N=150) voluntarily completed the Health Care Preferences Questionnaire to determine treatment preferences in response to the use of psychiatric medications, seclusion and restraint, and electroconvulsive therapy (ECT). A vignette was used to determine preferences first with respect to an imaginary patient and then with respect to the respondent. Results: Few participants were distressed by the psychiatric scenario (7%). In regard to their own care, in an emergency most participants supported the use of involuntary treatments (medications, 70%; medication injection, 76%; and seclusion and restraint, 73%), with the exception of ECT (quick treatment, 32%; if life is in danger, 60%). Participants were less likely to support treatments for themselves than for an imaginary patient. The majority (65%) identified specific medication preferences. Conclusions: Scenarios about the state of medical and psychiatric health are a feasible method of identifying treatment preferences. They are well tolerated and may serve as a model for assisting persons with serious mental illness in considering difficult treatment decisions. C1 [Foti, Mary Ellen] Univ Massachusetts, Sch Med, Dept Psychiat, Worcester, MA 01655 USA. [Van Citters, Aricca D.] Dartmouth Med Sch, Dartmouth Psychiat Res Ctr, Lebanon, NH USA. [Naidoo, Umadevi] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Foti, ME (reprint author), Univ Massachusetts, Sch Med, Dept Psychiat, 55 Lake Ave N, Worcester, MA 01655 USA. EM maryellen.foti@umassmed.edu NR 23 TC 10 Z9 10 U1 0 U2 1 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD NOV PY 2007 VL 58 IS 11 BP 1467 EP 1471 DI 10.1176/appi.ps.58.11.1467 PG 5 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 265LQ UT WOS:000253360800013 PM 17978258 ER PT J AU Guzik, LH Wirshing, DA AF Guzik, Lisa H. Wirshing, Donna A. TI Behavioral weight loss classes for patients with severe mental illness SO PSYCHIATRIC SERVICES LA English DT Editorial Material C1 [Guzik, Lisa H.; Wirshing, Donna A.] VA Greater Los Angeles Healthcare Ctr, Dept Psychiat, Los Angeles, CA 90073 USA. [Wirshing, Donna A.] Univ Calif Los Angeles, Sch Med, Dept Psychiat, Los Angeles, CA 90024 USA. RP Guzik, LH (reprint author), VA Greater Los Angeles Healthcare Ctr, Dept Psychiat, 11301 Wilshire Blvd,Bldg 210, Los Angeles, CA 90073 USA. EM lisa.guzik@gmail.com NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD NOV PY 2007 VL 58 IS 11 BP 1498 EP 1498 DI 10.1176/appi.ps.58.11.1498 PG 1 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 265LQ UT WOS:000253360800021 PM 17978266 ER PT J AU Recklitis, CJ Licht, I Ford, J Oeffinger, K Diller, L AF Recklitis, Christopher J. Licht, Ilana Ford, Jennifer Oeffinger, Kevin Diller, Lisa TI Screening adult survivors of childhood cancer with the distress thermometer: a comparison with the SCL-90-R SO PSYCHO-ONCOLOGY LA English DT Article DE cancer; oncology; pediatric; survivors; screening ID PSYCHOLOGICAL DISTRESS; DEPRESSION AB As the number of cancer survivors continues to grow, identification of brief, valid psychological screening measures will be a critical step in providing them with appropriate psychosocial care. The distress thermometer (DT) is a one-item distress screening that is recommended by the National Comprehensive Cancer Network (NCCN) for screening cancer patients, but has not been evaluated for cancer survivors. This study evaluated the validity of the DT compared to the Symptom Checklist-90-Revised (SCL-90-R) in a sample of 119 adult survivors of childhood cancer aged 18-45 (median=23.5). Results indicated that when using the NCCN suggested cut-off score of 5, the DT only identified 20 of the 36 SCL-90-R-positive cases of psychological distress (sensitivity 55.6%; specificity 80.7%). Using an alternative DT cut-off score of 4 identified 23 of the 36 SCL-90-R-positive cases (sensitivity 63.9%; specificity 65.1%). Receiver operating characteristics analysis indicated that the DT had only fair diagnostic utility relative to the SCL-90-R (AUC=0.72). Results do not support the validity of the DT in adult survivors of childhood cancer. Copyright (C) 2007 John Wiley & Sons, Ltd. C1 Perini Family Survivors Ctr, Dana Farber Canc Inst, Boston, MA 02115 USA. Suffolk Univ, Dept Psychol, Boston, MA 02114 USA. Mem Sloan Kettering Canc Ctr, Dept Psychiat & Behav Sci, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Dept Pediat, New York, NY 10021 USA. Univ Texas, SW Med Ctr, Dept Family Med, Tyler, TX 75708 USA. RP Recklitis, CJ (reprint author), Perini Family Survivors Ctr, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM Christopher_Recklitis@dfci.harvard.edu NR 20 TC 29 Z9 30 U1 1 U2 3 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1057-9249 J9 PSYCHO-ONCOL JI Psycho-Oncol. PD NOV PY 2007 VL 16 IS 11 BP 1046 EP 1049 DI 10.1002/pon.1212 PG 4 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 229QS UT WOS:000250819800010 PM 17506074 ER PT J AU Lombrozo, T Kelemen, D Zaitchik, D AF Lombrozo, Tania Kelemen, Deborah Zaitchik, Deborah TI Inferring design - Evidence of a preference for teleological explanations in patients with Alzheimer's disease SO PSYCHOLOGICAL SCIENCE LA English DT Article; Proceedings Paper CT 28th Annnual Conference of the Cognitive-Science-Society CY JUL, 2006 CL Vancouver, CANADA SP Cognit Sci Soc AB Unlike educated adults, young children demonstrate a "promiscuous" tendency to explain objects and phenomena by reference to functions, endorsing what are called teleological explanations. This tendency becomes more selective as children acquire increasingly coherent beliefs about causal mechanisms, but it is unknown whether a widespread preference for teleology is ever truly outgrown. The study reported here investigated this question by examining explanatory judgments in patients with Alzheimer's disease (AD), whose dementia affects the rich causal beliefs adults typically consult in evaluating explanations. The results indicate that unlike healthy adults, AD patients systematically and promiscuously prefer teleological explanations, suggesting that an underlying tendency to construe the world in terms of functions persists throughout life. This finding has broad relevance not only to understanding conceptual impairments in AD, but also to theories of development, learning, and conceptual change. Moreover, this finding sheds light on the intuitive appeal of creationism. C1 Univ Calif Berkeley, Dept Psychol, Berkeley, CA 94720 USA. Boston Univ, Dept Psychol, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. RP Lombrozo, T (reprint author), Univ Calif Berkeley, Dept Psychol, 3210 Tolman Hall, Berkeley, CA 94720 USA. EM lombrozo@berkeley.edu FU NIA NIH HHS [AG020548] NR 32 TC 68 Z9 68 U1 1 U2 9 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0956-7976 J9 PSYCHOL SCI JI Psychol. Sci. PD NOV PY 2007 VL 18 IS 11 BP 999 EP 1006 DI 10.1111/j.1467-9280.2007.02015.x PG 8 WC Psychology, Multidisciplinary SC Psychology GA 229MA UT WOS:000250806900013 PM 17958715 ER PT J AU Ditman, T Holcomb, PJ Kuperberg, GR AF Ditman, Tali Holcomb, Phillip J. Kuperberg, Gina R. TI An investigation of concurrent ERP and self-paced reading methodologies SO PSYCHOPHYSIOLOGY LA English DT Article DE event-related potentials; self-paced reading; P600; N400; language; sentence; methodology ID BRAIN POTENTIALS; SEMANTIC VIOLATIONS; TIME-COURSE; COMPREHENSION; SENTENCES; INDEPENDENCE; RESOLUTION AB Traditionally, event-related brain potential (ERP) studies of language processing have presented words at a fixed rate using rapid serial visual presentation. Recent studies suggest, however, that the processes engaged during sentence comprehension are contingent on word presentation rate. These findings underscore the importance of allowing participants to read at a natural pace. The present study employed simultaneous self- paced reading and ERP methodologies to examine behavioral and neural responses while participants read sentences containing pragmatic or morphosyntactic violations or no violations. ERP and self-paced reading results replicated previous findings. This novel combination of behavioral and ERP methodologies combines the high temporal resolution and direct neural measures offered by ERPs with the more natural reading environment and information about processing load provided by self- paced reading. C1 Tufts Univ, Dept Psychol, Medford, MA 02155 USA. Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. RP Ditman, T (reprint author), Tufts Univ, Dept Psychol, Psychol Bldg,490 Boston Ave, Medford, MA 02155 USA. EM tali.ditman@tufts.edu FU NICHD NIH HHS [R01 HD025889-17, R01 HD025889-16, R01 HD043251-04, R01 HD025889, R01 HD043251-05, R01 HD025889-18, R01 HD043251, HD043251, HD25889, R01 HD043251-02, R01 HD025889-19, R37 HD025889, R01 HD043251-01A1, R01 HD043251-03]; NIDCD NIH HHS [DC05237, R01 DC005237]; NIMH NIH HHS [R01 MH071635] NR 28 TC 22 Z9 23 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD NOV PY 2007 VL 44 IS 6 BP 927 EP 935 DI 10.1111/j.1469-8986.2007.00593.x PG 9 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 222DS UT WOS:000250276900011 PM 17850242 ER PT J AU Ditman, T Kuperberg, GR AF Ditman, Tali Kuperberg, Gina R. TI The time course of building discourse coherence in schizophrenia: An ERP investigation SO PSYCHOPHYSIOLOGY LA English DT Article DE schizophrenia; discourse; ERPs; language; inferences ID EVENT-RELATED POTENTIALS; LATENT SEMANTIC ANALYSIS; WORKING-MEMORY CAPACITY; LONG-TERM-MEMORY; THOUGHT-DISORDER; LINGUISTIC CONTEXT; BRAIN POTENTIALS; LANGUAGE; SENTENCES; COMPREHENSION AB Impairments in the buildup and use of context may lead to disorders of thought and language in schizophrenia. To test this hypothesis, event-related potentials (ERPs) were measured while patients and healthy controls read sentences that were highly causally related, intermediately related, or unrelated to preceding contexts. Although patients were slower than controls, both groups used the discourse context similarly as evidenced by similar reaction time patterns across conditions. Neurally however, different patterns emerged between patients and controls: within the N400 time window, patients failed to modulate their neural responses across conditions. This failure to differentiate between conditions was specifically correlated with positive thought disorder. Results suggest that schizophrenia patients, particularly those with positive thought disorder, fail to make immediate use of discourse context to build up semantic coherence in the brain. C1 Tufts Univ, Dept Psychol, Medford, MA 02155 USA. Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. RP Ditman, T (reprint author), Tufts Univ, Dept Psychol, Psychol Bldg,490 Boston Ave, Medford, MA 02155 USA. EM tali.ditman@tufts.edu FU NIMH NIH HHS [R01 MH071635] NR 73 TC 39 Z9 39 U1 2 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD NOV PY 2007 VL 44 IS 6 BP 991 EP 1001 DI 10.1111/j.1469-8986.2007.00565.x PG 11 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 222DS UT WOS:000250276900016 PM 17666031 ER PT J AU Dobscha, SK Corson, K Gerrity, MS AF Dobscha, Steven K. Corson, Kathryn Gerrity, Martha S. TI Depression treatment preferences of VA primary care patients SO PSYCHOSOMATICS LA English DT Article ID RANDOMIZED-TRIAL; MONITORING DEPRESSION; PHQ-9; MANAGEMENT; ADHERENCE; SYMPTOMS; OUTCOMES; IMPACT AB The authors identified veterans' depression treatment preferences and explored relationships between preferences, process of care, and clinical outcomes. Patients entering a collaborative depression intervention trial in primary care completed an assessment of treatment preferences. Medical record review was used to identify treatments offered and received over a 12-month period. Of 314 patients, 32% preferred antidepressants; 19%, individual counseling; 18%, antidepressants plus counseling; 7%, group counseling; and 25%, "watchful waiting." Although the treatment that was offered was associated with treatment preferences, being offered preferred treatment was not associated with receiving treatment or with changes in depression severity or satisfaction over time. C1 Portland VA Med Ctr, Ctr Study Chron Comorbid Mental & Phys Disorders, Portland, OR 97207 USA. RP Dobscha, SK (reprint author), Portland VA Med Ctr, Ctr Study Chron Comorbid Mental & Phys Disorders, POB 1034,R&D 66, Portland, OR 97207 USA. EM steven.dobscha@va.gov NR 32 TC 17 Z9 17 U1 4 U2 5 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD NOV-DEC PY 2007 VL 48 IS 6 BP 482 EP 488 DI 10.1176/appi.psy.48.6.482 PG 7 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 228OK UT WOS:000250739100004 PM 18071094 ER PT J AU Parker, LE de Pillis, E Altschuler, A Rubenstein, LV Meredith, LS AF Parker, Louise E. de Pillis, Emmeline Altschuler, Andrea Rubenstein, Lisa V. Meredith, Lisa S. TI Balancing participation and expertise: A comparison of locally and centrally managed health care quality improvement within primary care practices SO QUALITATIVE HEALTH RESEARCH LA English DT Article DE participation; expertise; quality improvement; depression; primary care ID TRANSFORMATION; SATISFACTION; PERFORMANCE; DEPRESSION; PHYSICIANS; DECISIONS; MEDICINE; BEHAVIOR; AUTONOMY; WORK AB In a longitudinal qualitative study, the authors evaluated two health care quality improvement (QI) methods that emphasized either participation (local approach) or expertise (central approach). They followed teams using these approaches to develop depression care QI programs for primary care practices over several years, observing their processes and outcomes and learning about participants' perceptions, beliefs, and experiences. Concordant with the literature, most participants preferred the local approach, but some were willing to relinquish some decision making to experts. Participants identified unique advantages of both the local (e.g., maximizes buy-in and local fit) and central (e.g., maximizes efficiency, reduces burden) approaches. The authors propose a hybrid model in which experts make strategic decisions about what practices to adopt and local site personal make tactical decisions about implementation. They believe that balancing participation and expertise provides the best formula for producing lasting QI for health care organizations across a wide variety of circumstances. C1 Ctr Mental Healthcare & Outcomes Res, Little Rock, AR USA. RAND Corp, Santa Monica, CA USA. Univ Hawaii, Coll Business & Econ, Hilo, HI 96720 USA. Kaiser Permanente, Div Res, Oakland, CA USA. VA Greater Los Angles, Los Angeles, CA USA. Univ Calif Los Angeles, Los Angeles, CA USA. Excellence Study Healthcare Provider Behav, VA Hlth Serv Res & Dev Ctr, Los Angeles, CA USA. RP Parker, LE (reprint author), Ctr Mental Healthcare & Outcomes Res, Little Rock, AR USA. EM parkerlouise@earthlink.net FU NIMH NIH HHS [U01-MH-50732] NR 39 TC 31 Z9 31 U1 0 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1049-7323 J9 QUAL HEALTH RES JI Qual. Health Res. PD NOV PY 2007 VL 17 IS 9 BP 1268 EP 1279 DI 10.1177/1049732307307447 PG 12 WC Information Science & Library Science; Social Sciences, Interdisciplinary; Social Sciences, Biomedical SC Information Science & Library Science; Social Sciences - Other Topics; Biomedical Social Sciences GA 224WN UT WOS:000250479000011 PM 17968043 ER PT J AU Thrall, JH AF Thrall, James H. TI Commentary on "Are We Really Practicing Medicine Today?" SO RADIOLOGY LA English DT Editorial Material ID APPENDICITIS; CT C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Thrall, JH (reprint author), Massachusetts Gen Hosp, Dept Radiol, MZ FND 216,Box 9657,14 Fruit St, Boston, MA 02114 USA. EM thrall.james@mgh.harvard.edu NR 5 TC 0 Z9 0 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD NOV PY 2007 VL 245 IS 2 BP 331 EP 332 DI 10.1148/radiol.2452070202 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 223BE UT WOS:000250343800006 PM 17940296 ER PT J AU Gazelle, GS Halpern, EF Ryan, HS Tramontano, AC AF Gazelle, G. Scott Halpern, Elkan F. Ryan, Heather S. Tramontano, Angela C. TI Utilization of diagnostic medical imaging: Comparison of radiologist referral versus same-specialty referral SO RADIOLOGY LA English DT Article ID POPULATION; PHYSICIANS AB Purpose:To retrospectively compare the frequency with which patients underwent diagnostic medical imaging procedures during episodes of outpatient medical care according to whether their physicians referred patients for imaging to themselves and/ or physicians in their same specialty or to radiologists. Materials and Methods: Institutional review board approval was not necessary for this HIPAA- compliant study. An insurance claims database from a large national employer- based health plan was obtained. Claims data from 1999 - 2003 were grouped into episodes of care for six conditions: cardiopulmonary disease, coronary and/ or cardiac disease, extremity fracture, knee pain, intraabdominal malignancy, and stroke. For each condition, each referring physician's behavior was categorized as either " same- specialty referral" or " radiologist referral" on the basis of that physician's entire history of imaging referrals for the condition. The frequency with which patients underwent diagnostic medical imaging procedures during episodes of care was compared according to whether their physicians referred patients for imaging to themselves and/ or same- specialty physicians or to radiologists. Rates were compared by using x(2) tests, and logistic regression was used to compare utilization rates, with patient age and number of comorbidities as covariates. Results: For the conditions evaluated, physicians who referred patients to themselves or to other same- specialty physicians for diagnostic imaging used imaging between 1.12 and 2.29 times as often, per episode of care, as physicians who referred patients to radiologists ( P <.005 for all comparisons). Adjusting for patient age and comorbidity, the likelihood of imaging was 1.196 - 3.228 times greater for patients cared forby same- specialty - referring physicians. Conclusion: Same- specialty - referring physicians tend to utilize imaging more frequently than do physicians who refer their patients to radiologists. These results cannot be explained by differences in case mix ( because analyses were performed within six specific conditions of interest), patient age, or comorbidity. C1 Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. RP Gazelle, GS (reprint author), Massachusetts Gen Hosp, Inst Technol Assessment, 101 Merrimac St,10th Floor, Boston, MA 02114 USA. NR 8 TC 58 Z9 58 U1 0 U2 2 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD NOV PY 2007 VL 245 IS 2 BP 517 EP 522 DI 10.1148/radiol.2452070193 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 223BE UT WOS:000250343800028 PM 17940306 ER PT J AU Upadhyay, R Sheth, RA Weissleder, R Mahmood, U AF Upadhyay, Rabi Sheth, Rahul A. Weissleder, Ralph Mahmood, Umar TI Quantitative real-time catheter-based fluorescence molecular imaging in mice SO RADIOLOGY LA English DT Article ID PROTEASE ACTIVITY; GENE-EXPRESSION; CANCER; FEASIBILITY; CALIBRATION AB Purpose:To prospectively evaluate an optical imaging system designed to perform quantitative, intravital catheter- based imaging of fluorescent molecular probes. Materials and Methods: This study was performed according to a protocol approved by the institutional animal care committee. A fiberoptic catheter imaging system was developed to implement a normalization algorithm for real- time quantitative nearinfrared ( NIR) imaging. The system was validated with in vitro imaging of fluorochrome phantoms and in vivo fluorescence measurements obtained in tumors implanted in murine abdomens ( n = 7) after administration of an enzyme- activatable NIR probe. Standard analysis of variance tests were used to determine significant dissimilarities in signal from distinct fluorochrome concentrations. The clinical utility of the system was further evaluated by imaging orthotopically implanted murine colonic adenocarcinomas ( n = 4). Results: Raw NIR fluorescence intensities, which were measured with a fiberoptic catheter placed above wells of varying NIR fluorochrome concentration, varied markedly ( > 100%) with catheter position, while the corrected NIR signal was confined to a range of values within 10% of their mean for each individual fluorochrome concentration and were significantly distinct ( P <.001) between relevant concentration ranges. Similar results were observed for the in vivo measurements from the abdominally implanted tumors, with raw NIR signal varying 20% from the mean and corrected NIR signal varying only 1% from the mean. The colonic studies revealed that the correction method was robust enough for use during minimally invasive imaging procedures. Conclusion: The authors have developed and implemented a method for quantitative real- time catheter- based fluorescence imaging that resolves NIR signal dependence on changes in catheter position. C1 Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Boston, MA 02114 USA. RP Mahmood, U (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, 185 Cambridge St, Simches 8226, Boston, MA 02114 USA. EM mahmood@helix.mgh.harvard.edu FU NCI NIH HHS [R24 CA92782]; NIBIB NIH HHS [R01 EB001872] NR 15 TC 35 Z9 36 U1 0 U2 2 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD NOV PY 2007 VL 245 IS 2 BP 523 EP 531 DI 10.1148/radiol.2452061613 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 223BE UT WOS:000250343800029 PM 17940307 ER PT J AU Chapman, VM AF Chapman, Vernon M. TI The anteater nose sign SO RADIOLOGY LA English DT Editorial Material ID EXTENSOR DIGITORUM BREVIS; TARSAL COALITION; CALCANEONAVICULAR COALITION; INTERPOSITION; RESECTION; CT C1 Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Chapman, VM (reprint author), Massachusetts Gen Hosp, Dept Radiol, 55 Fruit St,FND 216,POB 9657, Boston, MA 02114 USA. EM vernon.chapman@riaco.com NR 13 TC 2 Z9 3 U1 0 U2 1 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD NOV PY 2007 VL 245 IS 2 BP 604 EP 605 DI 10.1148/radiol.2452050010 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 223BE UT WOS:000250343800037 PM 17940313 ER PT J AU Thieke, C Kufer, KH Monz, M Scherrer, A Alonso, F Oelfke, U Huber, PE Debus, J Bortfeld, T AF Thieke, Christian Kuefer, Karl-Heinz Monz, Michael Scherrer, Alexander Alonso, Fernando Oelfke, Uwe Huber, Peter E. Debus, Juergen Bortfeld, Thomas TI A new concept for interactive radiotherapy planning with multicriteria optimization: First clinical evaluation SO RADIOTHERAPY AND ONCOLOGY LA English DT Article DE inverse planning system; IMRT; interactive; mutticriteria; multiobjective; clinical evaluation ID DOSE OPTIMIZATION; RADIATION-THERAPY; BEAM; BRACHYTHERAPY; ALGORITHM AB Background and purpose: Currently, inverse planning for intensity-modulated radiotherapy (IMRT) can be a timeconsuming trial and error process. This is because many planning objectives are inherently contradictory and cannot reach their individual optimum all at the same time. Therefore in clinical practice the potential of IMRT cannot be fully exploited for all patients. Multicriteria (multiobjective) optimization combined with interactive plan navigation is a promising approach to overcome these problems. Patients and methods: We developed a new inverse planning system called "Multicriteria Interactive Radiotherapy Assistant (MIRA)". The optimization result is a database of patient specific, Pareto-optimal plan proposals. The database is explored with an intuitive user interface that utilizes both a new interactive element for plan navigation and familiar dose visualizations in form of DVH and isoclose projections. Two clinical test cases, one paraspinal meningioma case and one prostate case, were optimized using MIRA and compared with the clinically approved planning program KonRad. Results: Generating the databases required no user interaction and took approx. 2-3 h per case. The interactive exploration required only a few minutes until the best plan was identified, resulting in a significant reduction of human planning time. The achievable plan quality was comparable to KonRad with the additional benefit of having plan alternatives at hand to perform a sensitivity analysis or to decide for a different clinical compromise. Conclusions: The MIRA system provides a complete database and interactive exploration of the solution space in real time. Hence, it is ideally suited for the inherently multicriterial problem of inverse IMRT treatment planning. (c) 2007 Elsevier Ireland Ltd. All rights reserved. C1 [Thieke, Christian; Huber, Peter E.] Deutsch Krebsforschungszentrum, Dept Radiat Oncol, D-6900 Heidelberg, Germany. [Thieke, Christian; Huber, Peter E.; Debus, Juergen] Univ Clin, Dept Radiooncol & Radiat Therapy, Heidelberg, Germany. [Kuefer, Karl-Heinz; Monz, Michael; Scherrer, Alexander; Alonso, Fernando] Fraunhofer Inst Ind Math, Dept Optimizat, Kaiserslautern, Germany. [Oelfke, Uwe] Deutsch Krebsforschungszentrum, Dept Med Phys Radiat Oncol, Heidelberg, Germany. [Bortfeld, Thomas] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Bortfeld, Thomas] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. RP Thieke, C (reprint author), German Canc Res Ctr, Dept Radiat Oncol, E050, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany. EM c.thieke@dkfz.de FU NCI NIH HHS [R01-CA103904] NR 23 TC 51 Z9 55 U1 0 U2 8 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-8140 J9 RADIOTHER ONCOL JI Radiother. Oncol. PD NOV PY 2007 VL 85 IS 2 BP 292 EP 298 DI 10.1016/j.radonc.2007.06.020 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 249BI UT WOS:000252201400018 PM 17892901 ER PT J AU Ullrich, P Jensen, M Loeser, J Cardenas, D AF Ullrich, Phil Jensen, Mark Loeser, John Cardenas, Diana TI Catastrophizing mediates associations between pain severity, psychological distress, and functional disability among persons with spinal cord injury SO REHABILITATION PSYCHOLOGY LA English DT Article DE pain; spinal cord injury; catastrophizing; distress; functioning ID COPING STRATEGIES; DEPRESSION; VALIDITY; QUESTIONNAIRE; INTERFERENCE; INDIVIDUALS; RELIABILITY; ADJUSTMENT; INTENSITY; IMPACT AB Objective: To examine associations between pain severity, psychological distress, catastrophizing, and indices of functional disability in a sample of persons with spinal cord injury (SCI). Catastrophizing was examined as a potential mediator of associations between pain severity, psychological distress, and functional disability. Design and Participants: Questionnaires assessing pain severity, psychological distress, catastrophizing, pain interference, and community integration were completed by 237 persons with SCI. Results: Psychological distress and pain severity were associated significantly with greater functional disability. Moreover, the association between pain severity and functional disability was strongest among persons with high psychological distress. Catastrophizing appeared to mediate the associations between pain severity, psychological distress, and functional disability. Conclusions: Pain severity and psychological distress have the potential for both direct and interactive effects on functional disability, possibly through the mediating effects of catastrophizing. C1 Vet Affairs Puget Sound Healthcare Syst, Dept Vet Affairs, Spinal Cord Injury Qual Enhancement Res Initiat, Spinal Cord Injury & Disorders Strateg Healthcare, Seattle, WA 98101 USA. Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. Univ Washington, Dept Neurol Surg, Seattle, WA 98195 USA. Univ Miami, Dept Rehabil Med, Coral Gables, FL 33124 USA. RP Ullrich, P (reprint author), Vet Affairs Puget Sound Healthcare Syst, Dept Vet Affairs, Spinal Cord Injury Qual Enhancement Res Initiat, Spinal Cord Injury & Disorders Strateg Healthcare, 1100 Olive Way,Suite 1400, Seattle, WA 98101 USA. EM philip.ullrich@va.gov NR 36 TC 4 Z9 4 U1 2 U2 5 PU EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA SN 0090-5550 J9 REHABIL PSYCHOL JI Rehabil. Psychol. PD NOV PY 2007 VL 52 IS 4 BP 390 EP 398 DI 10.1037/0090-5550.52.4.390 PG 9 WC Psychology, Clinical; Rehabilitation SC Psychology; Rehabilitation GA 233QG UT WOS:000251104800004 ER PT J AU Kacmarek, RM AF Kacmarek, Robert M. TI Noninvasive positive-pressure ventilation in postoperative hypoxemic respiratory failure - With a helmet? SO RESPIRATORY CARE LA English DT Editorial Material ID OBSTRUCTIVE PULMONARY-DISEASE; RANDOMIZED CONTROLLED-TRIAL; ACUTE EXACERBATION; AIRWAY PRESSURE; EXTUBATION; RISK C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Resp Care Serv, Boston, MA 02115 USA. RP Kacmarek, RM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Resp Care Serv, Boston, MA 02115 USA. EM rkacmarek@partners.org NR 16 TC 1 Z9 1 U1 0 U2 0 PU DAEDALUS ENTERPRISES INC PI IRVING PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA SN 0020-1324 J9 RESP CARE JI Respir. Care PD NOV PY 2007 VL 52 IS 11 BP 1451 EP 1453 PG 3 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 229FJ UT WOS:000250788200001 PM 17971245 ER PT J AU Hess, DR AF Hess, Dean R. TI Noninvasive positive-pressure ventilation: A silver bullet for extubation failure? SO RESPIRATORY CARE LA English DT Editorial Material ID OBSTRUCTIVE PULMONARY-DISEASE; RANDOMIZED CONTROLLED-TRIAL; RESPIRATORY-FAILURE; MECHANICAL VENTILATION; INSUFFICIENCY; METAANALYSIS; SUPPORT; RISK C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Resp Care, Boston, MA 02115 USA. Univ Calgary, Dept Crit Care Med, Calgary, AB, Canada. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Resp Acute Care Unit, Boston, MA USA. RP Hess, DR (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Resp Care, Boston, MA 02115 USA. EM dhess@partners.org NR 21 TC 5 Z9 5 U1 0 U2 0 PU DAEDALUS ENTERPRISES INC PI IRVING PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA SN 0020-1324 J9 RESP CARE JI Respir. Care PD NOV PY 2007 VL 52 IS 11 BP 1454 EP 1456 PG 3 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 229FJ UT WOS:000250788200002 PM 17971246 ER PT J AU Kreider, ME Grippi, MA AF Kreider, Mary Elizabeth Grippi, Michael A. TI Impact of the new ATS/ERS pulmonary function test interpretation guidelines SO RESPIRATORY MEDICINE LA English DT Article DE diagnosis; guideline adherence; lung diseases; obstructive; pulmonary function tests ID LUNG-FUNCTION TESTS; STANDARDIZATION; STRATEGIES AB Rationale: In November 2005, the American Thoracic and European Respiratory Societies jointly published a statement proposing a new interpretation scheme for pulmonary function tests. The practical effect of adoption of these new guidelines has not yet been studied. The purpose of the current study was to address the effects of the new interpretation strategy on the relative distribution of obstructive and restrictive diagnoses in patients evaluated at a single academic medical center laboratory. Patients/Methods: Pulmonary functions tests from 319 patients were analyzed according to four different interpretation schemes. The number of patients classified according to each as obstructed, restricted, neither, or both were compared, and factors associated with a change in classification using the different approaches were examined. Results: Although similar proportions of patients were identified as restricted using either the "GOLD" scheme (23%) or new approaches (22%), significantly more (P<0.005) were defined as obstructed using the newly proposed scheme (44% versus 33%). Additionally, 36% of subjects defined as obstructed using either the traditional or new schemes were classified differently (i.e., either "gained" or "lost" the diagnosis of obstruction) using the new approach. Women were significantly more likely than men to have a change in classification. Conclusions: The new interpretation scheme leads to a diagnosis of obstruction in a greater proportion of patients undergoing pulmonary function testing. The clinical significance of this finding has not yet been validated, and its economic impact remains to be assessed. (C) 2007 Elsevier Ltd. All rights reserved. C1 Hosp Univ Penn, Dept Med, Div Pulm Allergy & Crit Care Med, Philadelphia, PA 19104 USA. Philadelphia VA Med Ctr, Philadelphia, PA USA. RP Kreider, ME (reprint author), Univ Penn, Sch Med, Div Pulm Allergy & Crit Care Med, 828 Gates Bldg,3400 Spruce St, Philadelphia, PA 19104 USA. EM kreiderm@mail.med.upenn.edu; grippi@mail.med.upenn.edu NR 13 TC 12 Z9 12 U1 2 U2 3 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0954-6111 J9 RESP MED JI Respir. Med. PD NOV PY 2007 VL 101 IS 11 BP 2336 EP 2342 DI 10.1016/j.rmed.2007.06.019 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System SC Cardiovascular System & Cardiology; Respiratory System GA 223BH UT WOS:000250344100015 PM 17686622 ER PT J AU Kim, JH Bertram, KM Quirk, MT Arroyo, JG AF Kim, Joon-Hyun Bertram, Kurt M. Quirk, Matthew T. Arroyo, Jorge G. TI Modified external needle drainage of subretinal fluid in primary rhegmatogenous retinal detachment SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES LA English DT Article DE needle drainage; retinal detachment; scleral buckle; subretinal fluid drainage ID ARGON-LASER CHOROIDOTOMY; SCLERAL BUCKLING PROCEDURES; INSTRUMENT; TRIAL AB Purpose: We describe surgical outcomes in a single-surgeon, consecutive series of patients who received scleral buckle placement for primary retinal detachment using a modified external needle drainage technique. Methods: Eighty-two eyes of 80 patients with primary retinal detachment underwent scleral buckle placement with modified external needle drainage. Preoperative, postoperative, and surgical data were collected. Regression analysis was used to evaluate the association between preoperative clinical data and number of surgeries. Results: The retinal detachment most commonly involved 41% to 50% of the retina. Seventy-six eyes (92.7%) were repaired after 1 surgical procedure, 98.8%, after 2 procedures, and 100%, after 3 procedures. No preoperative clinical variables were found to be significantly correlated with the number of surgeries performed. Vision improved an average of 0.3 logarithm of the minimal angle of resolution or 3 lines of vision (P < 0.001). One eye (1.2%) developed a localized subretinal hemorrhage at the drainage site that resolved spontaneously. Conclusions: The modified external needle drainage technique used during scleral buckle placement appears to be safe and effective in patients with primary retinal. detachment. C1 Beth Israel Deaconess Med Ctr, Dept Ophthalmol, Boston, MA USA. Massachusetts Eye & Ear Infirm, Harvard Med Sch, Boston, MA 02114 USA. RP Arroyo, JG (reprint author), Beth Israel Deaconess Med Ctr, Div Ophthalmol, Retina Serv, Shapiro 5th Flr,330 Brookline Ave, Boston, MA 02215 USA. EM jarroyo@bidmc.harvard.edu NR 35 TC 6 Z9 6 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0275-004X J9 RETINA-J RET VIT DIS JI Retin.-J. Retin. Vitr. Dis. PD NOV-DEC PY 2007 VL 27 IS 9 BP 1231 EP 1237 PG 7 WC Ophthalmology SC Ophthalmology GA 238NS UT WOS:000251455100013 PM 18046230 ER PT J AU Stone, JH AF Stone, John H. TI Sailing the vasculitis sea SO RHEUMATIC DISEASE CLINICS OF NORTH AMERICA LA English DT Editorial Material C1 Massachusetts Gen Hosp, Rheumat Dis Unit, Boston, MA 02115 USA. RP Stone, JH (reprint author), Massachusetts Gen Hosp, Rheumat Dis Unit, Boston, MA 02115 USA. EM jhstone@partners.org NR 0 TC 0 Z9 0 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 0889-857X J9 RHEUM DIS CLIN N AM JI Rheum. Dis. Clin. North Am. PD NOV PY 2007 VL 33 IS 4 BP XI EP XIII DI 10.1016/j.rdc.2007.09.003 PG 3 WC Rheumatology SC Rheumatology GA 247DF UT WOS:000252056700001 ER PT J AU Stone, JH AF Stone, John H. TI Vasculitis: A collection of pearls and myths SO RHEUMATIC DISEASE CLINICS OF NORTH AMERICA LA English DT Review ID GIANT-CELL ARTERITIS; ANTINEUTROPHIL CYTOPLASMIC ANTIBODIES; CHURG-STRAUSS-SYNDROME; OBLITERANS BUERGERS-DISEASE; SMALL-VESSEL VASCULITIS; OF-THE-LITERATURE; WEGENERS-GRANULOMATOSIS; THROMBOANGIITIS-OBLITERANS; TEMPORAL ARTERITIS; BEHCETS-DISEASE AB Since Kussmaul and Maier described the index case of vasculitis in 1866 the field has seen many changes. What was considered for decades to be only a single disorder is now known to consist of at least 15 to 20 distinct conditions. Important strides have been made in unraveling the pathophysiology of some individual forms of vasculitis, but many mysteries remain. Over time, numerous myths and occasional pearls have arisen from the care of patients with these disorders. This collection of pearls and myths gathers lessons about the status of clinical care of vasculitis patients in the year 2008. C1 Massachusetts Gen Hosp, Rheumatol Unit, Boston, MA 02114 USA. RP Stone, JH (reprint author), Massachusetts Gen Hosp, Rheumatol Unit, 55 Fruit St, Boston, MA 02114 USA. EM jhstone@partners.org NR 118 TC 17 Z9 18 U1 1 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0889-857X J9 RHEUM DIS CLIN N AM JI Rheum. Dis. Clin. North Am. PD NOV PY 2007 VL 33 IS 4 BP 691 EP + DI 10.1016/j.rdc.2007.09.002 PG 50 WC Rheumatology SC Rheumatology GA 247DF UT WOS:000252056700002 PM 18037113 ER PT J AU Schutt, RK Seidman, LJ Caplan, B Martsinkiv, A Goldfinger, SM AF Schutt, Russell K. Seidman, Larry J. Caplan, Brina Martsinkiv, Anna Goldfinger, Stephen M. TI The role of neurocognition and social context in predicting community functioning among formerly homeless seriously mentally ill persons SO SCHIZOPHRENIA BULLETIN LA English DT Article DE neurocognition; executive function; community functioning; homeless; housing; social environment ID CARD SORTING TEST; FOLLOW-UP; SUBSTANCE-ABUSE; SCHIZOPHRENIA; DEFICITS; DYSFUNCTION; COGNITION; SYMPTOMS; ILLNESS; HEALTH AB Objective: To test the influence of neurocognitive functioning on community functioning among formerly homeless persons with serious mental illness and to determine whether that influence varies with social context, independent of individual characteristics. Methods: In metropolitan Boston, 112 persons in Department of Mental Health shelters were administered a neuropsychological test battery and other measures and then randomly assigned to empowerment-oriented group homes or independent apartments, as part of a longitudinal study of the effects of housing on multiple outcomes. Subjects' case managers completed Rosen's 5-dimensional Life Skills Inventory at 3, 6, 12, and 18 months and subjects reported on their social contacts at baseline, 6, 12, and 18 months. Subject characteristics are controlled in the analysis. Results: Three dimensions of neurocognitive functioning-executive function, verbal declarative memory, and vigilance-each predicted community functioning. Better executive function predicted improved self-care and less turbulent behavior among persons living alone, better memory predicted more positive social contacts for those living in a group home, and higher levels of vigilance predicted improved communication in both housing types. Conclusion: Neurocognition predicts community functioning among homeless persons with severe mental illness, but in a way that varies with the social context in which community functioning occurs. C1 Harvard Univ, Beth Israel Deaconess Med Ctr, Massachusetts Mental Hlth Ctr, Dept Psychiat,Publ Psychiat Div, Boston, MA 02215 USA. Univ Massachusetts, Dept Sociol, Boston, MA 02125 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. Univ Massachusetts, Grad Program Appl Sociol, Boston, MA 02125 USA. SUNY Hlth Sci Ctr, Brooklyn, NY 11203 USA. RP Schutt, RK (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Massachusetts Mental Hlth Ctr, Dept Psychiat,Publ Psychiat Div, Landmark Ctr 2E,401 Pk Dr, Boston, MA 02215 USA. EM rschutt@bidmc.harvard.edu FU NIMH NIH HHS [R18MH4808001] NR 52 TC 8 Z9 8 U1 1 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD NOV PY 2007 VL 33 IS 6 BP 1388 EP 1396 DI 10.1093/schbul/sbm037 PG 9 WC Psychiatry SC Psychiatry GA 227VR UT WOS:000250686400019 PM 17483102 ER PT J AU Traum, AZ Schachter, AD AF Traum, Avram Z. Schachter, Asher D. TI Proteomic analysis in pediatric renal disease SO SEMINARS IN NEPHROLOGY LA English DT Review DE pediatrics; urine proteomics; noninvasive; biomarkers ID TANDEM MASS-SPECTROMETRY; AMINO-ACID OXIDATION; URINARY PROTEOME; NEPHROTIC SYNDROME; PRIMARY CULTURES; PROTEINS; AMMONIA; PHOSPHORYLATION; ASTROCYTES; NEURONS AB Children with renal disease have tremendous potential for recovery, particularly when disease processes are detected early in the disease course. However, invasive diagnostic maneuvers can be challenging, especially in younger children who may require general anesthesia. Urine proteomics technologies present an opportunity to discover noninvasive yet informative diagnostic and prognostic markers of renal disease in children. In this article we review current concepts regarding the normal urine protcome, followed by an overview of urine proteomics as applied to nephrotic syndrome, and conclude with a discussion of some of the challenges of performing proteomic profiling on nephrotic urine, with its inherent abundance of proteins. C1 [Traum, Avram Z.] Massachusetts Gen Hosp, Pediat Nephrol Unit, Boston, MA 02114 USA. [Schachter, Asher D.] Childrens Hosp, Harvard MIT Div Hlth Sci Technol, Childrens Hosp Informat Program, Div Nephrol, Boston, MA USA. [Traum, Avram Z.; Schachter, Asher D.] Harvard Med Sch, Boston, MA USA. RP Traum, AZ (reprint author), Massachusetts Gen Hosp, Pediat Nephrol Unit, 55 Fruit St, Boston, MA 02114 USA. EM atraum@partners.org FU NIDDK NIH HHS [T32 DK007726] NR 26 TC 4 Z9 4 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 0270-9295 J9 SEMIN NEPHROL JI Semin. Nephrol. PD NOV PY 2007 VL 27 IS 6 BP 652 EP 657 DI 10.1016/j.seninephrol.2007.09.009 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 242RE UT WOS:000251742400009 PM 18061847 ER PT J AU Brass, SD Copen, WA AF Brass, Steven D. Copen, William A. TI Neurological disorders in pregnancy from a neuroimaging perspective SO SEMINARS IN NEUROLOGY LA English DT Review DE pregnancy; stroke; cortical venous thrombosis; eclampsia; choriocarcinoma; brain tumor ID DIFFUSION-WEIGHTED MR; THROMBOTIC THROMBOCYTOPENIC PURPURA; REVERSIBLE POSTERIOR LEUKOENCEPHALOPATHY; ATTENUATED INVERSION-RECOVERY; PLANAR MAGNETIC-RESONANCE; WERNICKE ENCEPHALOPATHY; CHILDHOOD-CANCER; ACUTE STROKE; LYMPHOCYTIC ADENOHYPOPHYSITIS; CEREBRAL VASOCONSTRICTION AB Pregnancy can precipitate new neurological diseases as a result of the alterations in physiology that accompany the pregnant state. The pregnant patient presenting with neurological problems poses both diagnostic and therapeutic challenges, often forcing the clinician to rely on neuroimaging as part of the workup. This review discusses potential risks to the embryo and fetus posed by computed tomography (CT) and magnetic resonance imaging (MRI), the imaging studies most often used to study the central nervous system. Imaging features of a variety of neurological conditions associated with pregnancy are discussed, including pre-eclampsia and eclampsia, Wernicke's encephalopathy, cerebral venous thrombosis, ischemic stroke, postpartum angiopathy, and lymphocytic hypophysitis. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Neuroradiol, Boston, MA 02114 USA. RP Brass, SD (reprint author), Massachusetts Gen Hosp, Dept Neurol, 55 Fruit St,Wang Bldg,Suite 835, Boston, MA 02114 USA. EM sbrass@partners.org NR 104 TC 9 Z9 10 U1 0 U2 2 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0271-8235 J9 SEMIN NEUROL JI Semin. Neurol. PD NOV PY 2007 VL 27 IS 5 BP 411 EP 424 DI 10.1055/s-2007-991123 PG 14 WC Clinical Neurology SC Neurosciences & Neurology GA 224XU UT WOS:000250482500003 PM 17940920 ER PT J AU Yoon, LS Palmer, WE Kassarjian, A AF Yoon, Luke S. Palmer, William E. Kassarjian, Ara TI Evaluation of radial-sequence imaging in detecting acetabular labral tears at hip MR arthrography SO SKELETAL RADIOLOGY LA English DT Article DE hip; MRI; arthrography ID MAGNETIC-RESONANCE ARTHROGRAPHY; LESIONS; IMPINGEMENT AB Objective In recent years, radial imaging has been advocated for improved visualization of the acetabular labrum in magnetic resonance arthrography of the hip. The purpose of this study was to investigate whether radial imaging demonstrates labral tears not visible on standard imaging planes. Methods Fifty-four consecutive magnetic resonance (MR) arthrograms of the hip that included radial imaging over 2 years were retrospectively analyzed by two radiologists. Standard imaging planes and radial imaging were reviewed for identification of labral tears in four specific areas of the labrum: anterosuperior, posterosuperior, anteroinferior, and posteroinferior. The standard imaging sequences include fat-saturated spin-echo T1-weighted images in the coronal and oblique axial planes, non-fat-saturated T1-weighted images in the coronal and sagittal planes, and T2-weighted sequence in the axial plane. Radial imaging was performed as previously described using fat-saturated T1-weighted sequences. Results Using standard imaging planes, 50 anterosuperior, 31 posterosuperior, 10 anteroinferior, and 9 posteroinferior labral tears were detected in 54 MR arthrograms of the hip. Using radial sequences alone, 44 anterosuperior, 25 posterosuperior, 9 anteroinferior, and 5 posteroinferior labral tears were detected. In all four areas of the labrum, the radial imaging did not show any labral tear not seen on standard imaging planes. Discussion In MR arthrography of the hip, radial imaging did not reveal any additional labral tears. Standard imaging planes sufficiently demonstrate all acetabular labral tears. C1 Massachusetts Gen Hosp, Dept Radiol, Div Musculoskeletal Radiol, Boston, MA 02114 USA. RP Yoon, LS (reprint author), Massachusetts Gen Hosp, Dept Radiol, Div Musculoskeletal Radiol, 55 Fruit St,Founders 216, Boston, MA 02114 USA. EM yoon.luke@mgh.harvard.edu NR 18 TC 25 Z9 30 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0364-2348 J9 SKELETAL RADIOL JI Skeletal Radiol. PD NOV PY 2007 VL 36 IS 11 BP 1029 EP 1033 DI 10.1007/s00256-007-0363-x PG 5 WC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging SC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging GA 215PV UT WOS:000249822400003 PM 17712555 ER PT J AU Morgenthaler, TI Lee-Chiong, T Alessi, C Friedman, L Aurora, RN Boehlecke, B Brown, T Chesson, AL Kapur, V Maganti, R Owens, J Pancer, J Swick, TJ Zak, R AF Morgenthaler, Timothy I. Lee-Chiong, Teofilo Alessi, Cathy Friedman, Leah Aurora, R. Nisha Boehlecke, Brian Brown, Terry Chesson, Andrew L., Jr. Kapur, Vishesh Maganti, Rama Owens, Judith Pancer, Jeffrey Swick, Todd J. Zak, Rochelle CA Stand Practice Comm AASM TI Practice parameters for the clinical evaluation and treatment of circadian rhythm sleep disorders SO SLEEP LA English DT Review DE circadian; light therapy; melatonin; naps; jet lag; shift work ID SIMULATED NIGHT-SHIFT; BRIGHT LIGHT TREATMENT; DOUBLE-BLIND TRIAL; PLACEBO-CONTROLLED TRIAL; 5 TIME ZONES; JET-LAG; PHASE SYNDROME; MELATONIN TREATMENT; WAKE SYNDROME; ALZHEIMERS-DISEASE AB The expanding science of circadian rhythm biology and a growing literature in human clinical research on circadian rhythm sleep disorders (CRSDs) prompted the American Academy of Sleep Medicine (AASM) to convene a task force of experts to write a review of this important topic. Due to the extensive nature of the disorders covered, the review was written in two sections. The first review paper, in addition to providing a general introduction to circadian biology, addresses "exogenous" circadian rhythm sleep disorders, including shift work disorder (SWD) and jet lag disorder (JLD). The second review paper addresses the "endogenous" circadian rhythm sleep disorders, including advanced sleep phase disorder (ASPD), delayed sleep phase disorder (DSPD), irregular sleep-wake rhythm (ISWR), and the non-24-hour sleep-wake syndrome (nonentrained type) or free-running disorder (FRD). These practice parameters were developed by the Standards of Practice Committee and reviewed and approved by the Board of Directors of the AASM to present recommendations for the assessment and treatment of CRSDs based on the two accompanying comprehensive reviews. The main diagnostic tools considered include sleep logs, actigraphy, the Morningness-Eveningness Questionnaire (MEQ), circadian phase markers, and polysomnography. Use of a sleep log or diary is indicated in the assessment of patients with a suspected circadian rhythm sleep disorder (Guideline). Actigraphy is indicated to assist in evaluation of patients suspected of circadian rhythm disorders (strength of recommendation varies from "Option" to "Guideline," depending on the suspected CRSD). Polysomnography is not routinely indicated for the diagnosis of CRSDs, but may be indicated to rule out another primary sleep disorder (Standard). There is insufficient evidence to justify the use of MEQ for the routine clinical evaluation of CRSDs (Option). Circadian phase markers are useful to determine circadian phase and confirm the diagnosis of FRD in sighted and unsighted patients but there is insufficient evidence to recommend their routine use in the diagnosis of SWD, JLD, ASPD, DSPD, or ISWR (Option). Additionally, actigraphy is useful as an outcome measure in evaluating the response to treatment for CRSDs 1 Guideline). A range of therapeutic interventions were considered including planned sleep schedules, timed light exposure, timed melatonin doses, hypnotics, stimulants, and alerting agents. Planned or prescribed sleep schedules are indicated in SWD (Standard) and in JLD, DSPD, ASPD, ISWR (excluding elderly-demented/nursing home residents), and FRD (Option). Specifically dosed and timed light exposure is indicated for each of the circadian disorders with variable success (Option). Timed melatonin administration is indicated for JLD (Standard); SWD, DSPD, and FRD) in unsighted persons (Guideline); and for ASPD, FRD in sighted individuals, and for ISWR in children with moderate to severe psychomotor retardation (Option). Hypnotic medications may be indicated to promote or improve daytime sleep among night shift workers (Guideline) and to treat jet lag-induced insomnia (Option). Stimulants may be indicated to improve alertness in JLD and SWD (Option) but may have risks that must be weighed prior to use. Modafinil may be indicated to improve alertness during the night shift for patients with SWD (Guideline). C1 Mayo Clin, Mayo Sleep Disorders Ctr, Rochester, MN USA. Natl Jewish Med & Res Ctr, Denver, CO USA. Univ Calif Los Angeles, Greater Los Angeles VA Healthcare Syst, Sepulveda, CA USA. Stanford Univ, Sch Med, Dept Psychiat, Stanford, CA 94305 USA. Mt Sinai Med Ctr, Ctr Sleep Med, New York, NY 10029 USA. Louisiana State Univ, Med Ctr, Dept Neurol, Shreveport, LA 71105 USA. Univ Washington, Sleep Disorders Ctr Harborview, Seattle, WA 98195 USA. Barrow Neurol Inst, Dept Neurol, Phoenix, AZ 85013 USA. Rhode Isl Hosp, Dept Ped Ambulatory Pediatr, Providence, RI USA. Methodist Hosp, Methodist Neurol Inst, Houston, TX 77030 USA. RP Morgenthaler, TI (reprint author), Amer Acad Sleep Med, Standards Practice Committee, Westbrook Corp Ctr 1, Suite 920, Westchester, IL 60154 USA. EM aasm@aasmnet.org RI Kapur, Vishesh/K-1054-2014; OI Kapur, Vishesh/0000-0002-5417-1097; Morgenthaler, Timothy/0000-0002-2614-3793 NR 133 TC 193 Z9 197 U1 11 U2 45 PU AMER ACAD SLEEP MEDICINE PI WESTCHESTER PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA SN 0161-8105 J9 SLEEP JI Sleep PD NOV 1 PY 2007 VL 30 IS 11 BP 1445 EP 1459 PG 15 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 228IW UT WOS:000250724600006 PM 18041479 ER PT J AU Ay, H Benner, T Arsava, EM Furie, KL Singhal, AB Jensen, MB Ayata, C Towfighi, A Smith, EE Chong, JY Koroshetz, WJ Sorensen, AG AF Ay, Hakan Benner, Thomas Arsava, E. Murat Furie, Karen L. Singhal, Aneesh B. Jensen, Matt B. Ayata, Cenk Towfighi, Amytis Smith, Eric E. Chong, Ji Y. Koroshetz, Walter J. Sorensen, A. Gregory TI A computerized algorithm for etiologic classification of ischemic stroke - The causative classification of stroke system SO STROKE LA English DT Article DE classification cerebral infarct; etiology ID CAROTID-ARTERY STENOSIS; INTEROBSERVER AGREEMENT; CEREBRAL INFARCTION; RELIABILITY; COAGULATION; DIAGNOSIS; REGISTRY; DISEASE; HEALTH; TRIAL AB Background and Purpose - The SSS-TOAST is an evidence-based classification algorithm for acute ischemic stroke designed to determine the most likely etiology in the presence of multiple competing mechanisms. In this article, we present an automated version of the SSS-TOAST, the Causative Classification System (CCS), to facilitate its utility in multicenter settings. Methods - The CCS is a web-based system that consists of questionnaire-style classification scheme for ischemic stroke (http://ccs.martinos.org). Data entry is provided via checkboxes indicating results of clinical and diagnostic evaluations. The automated algorithm reports the stroke subtype and a description of the classification rationale. We evaluated the reliability of the system via assessment of 50 consecutive patients with ischemic stroke by 5 neurologists from 4 academic stroke centers. Results - The kappa value for inter-examiner agreement was 0.86 (95% CI, 0.81 to 0.91) for the 5-item CCS (large artery atherosclerosis, cardio-aortic embolism, small artery occlusion, other causes, and undetermined causes), 0.85 (95% CI, 0.80 to 0.89) with the undetermined group broken into cryptogenic embolism, other cryptogenic, incomplete evaluation, and unclassified groups (8-item CCS), and 0.80 (95% CI, 0.76 to 0.83) for a 16-item breakdown in which diagnoses were stratified by the level of confidence. The intra-examiner reliability was 0.90 (0.75-1.00) for 5-item, 0.87 (0.73-1.00) for 8-item, and 0.86 (0.75-0.97) for 16-item CCS subtypes. Conclusions - The web-based CCS allows rapid analysis of patient data with excellent intra-and inter-examiner reliability, suggesting a potential utility in improving the fidelity of stroke classification in multicenter trials or research databases in which accurate subtyping is critical. C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Stroke Serv,Dept Neurol, Boston, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,AA Martinos Ctr Biomed Imaging, Boston, MA 02129 USA. Univ Calif San Diego, Stroke Ctr, San Diego, CA 92103 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol & Stroke, Boston, MA 02129 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Neurovasc Regulat Lab,Dept Radiol, Boston, MA 02129 USA. Univ Calif Los Angeles, Med Ctr, Stroke Ctr, Dept Neurol, Los Angeles, CA 90024 USA. Columbia Univ, Dept Neurol, Div Stroke & Crit Care, New York, NY USA. NINCDS, NIH, Bethesda, MD 20892 USA. RP Ay, H (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Radiol,AA Martinos Ctr Biomed Imaging, 149 13th St,Room 2301, Boston, MA 02129 USA. EM hay@partners.org RI Arsava, Ethem Murat/I-9197-2013; Smith, Eric/C-5443-2012 OI Arsava, Ethem Murat/0000-0002-6527-4139; Smith, Eric/0000-0003-3956-1668 FU AHRQ HHS [R01-HS11392-02]; NCRR NIH HHS [P41-RR14075]; NINDS NIH HHS [R01-NS38477-04] NR 23 TC 155 Z9 160 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD NOV PY 2007 VL 38 IS 11 BP 2979 EP 2984 DI 10.1161/STROKEAHA.107.490896 PG 6 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 225LB UT WOS:000250518300019 PM 17901381 ER PT J AU Castillo, CFD AF Castillo, Carlos Fernandez-del TI Consensus defining postpancreatectomy complications: An opportunity we cannot ignore SO SURGERY LA English DT Editorial Material ID INTERNATIONAL STUDY-GROUP; PANCREATECTOMY C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Castillo, CFD (reprint author), Massachusetts Gen Hosp, 15 Parkman St,ACC 460, Boston, MA 02114 USA. EM cfernandez@partners.org NR 6 TC 1 Z9 1 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0039-6060 J9 SURGERY JI Surgery PD NOV PY 2007 VL 142 IS 5 BP 771 EP 772 DI 10.1016/j.surg.2007.08.013 PG 2 WC Surgery SC Surgery GA 232LV UT WOS:000251022100016 ER PT J AU Faris, JE Moore, AF Daniels, GH AF Faris, Jason E. Moore, Allan F. Daniels, Gilbert H. TI Sunitinib (sutent)-induced thyrotoxicosis due to destructive thyroiditis: A case report SO THYROID LA English DT Article ID RENAL-CELL CARCINOMA; HYPOTHYROIDISM; THERAPY AB Numerous drugs have been associated with destructive thyroiditis (subacute thyroiditis). Sunitinib, a tyrosine kinase inhibitor employed in renal cell carcinoma and gastrointestinal stromal tumors, has recently been linked to destructive thyroiditis with resultant hypothyroidism. We report a patient with transient overt thyrotoxicosis followed by hypothyroidism, apparently related to sunitinib therapy. C1 Massachusetts Gen Hosp, Thyroid Unit, Wang Ambulatory Care Ctr 730, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Internal Med, Boston, MA USA. Massachusetts Gen Hosp, Div Endocrinol, Boston, MA USA. RP Daniels, GH (reprint author), Massachusetts Gen Hosp, Thyroid Unit, Wang Ambulatory Care Ctr 730, 15 Parkman St, Boston, MA 02114 USA. EM gdaniels@partners.org NR 14 TC 37 Z9 38 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1050-7256 J9 THYROID JI Thyroid PD NOV PY 2007 VL 17 IS 11 BP 1147 EP 1149 DI 10.1089/thy.2007.0104 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 238KE UT WOS:000251445700019 PM 17714037 ER EF