FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Huh, W Raney, RB Hawkins, D Hayes-Jordan, A Million, L Rodeberg, D Teot, L Anderson, J AF Huh, Winston Raney, R. Beverly Hawkins, Douglas Hayes-Jordan, Andrea Million, Lynn Rodeberg, David Teot, Lisa Anderson, James TI ORBITAL RHABDOMYOSARCOMA (RMS): OUTCOME OF PATIENTS WHO RELAPSED FOLLOWING TREATMENT FOR LOCALIZED TUMORS ON INTERGROUP RHABDOMYOSARCOMA STUDY GROUP (IRSG) PROTOCOLS - III AND -IV, 1984-1997 SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Huh, Winston; Raney, R. Beverly; Hayes-Jordan, Andrea] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Hawkins, Douglas] Seattle Childrens Hosp, Seattle, WA USA. [Million, Lynn] Primary Childrens Med Ctr, Salt Lake City, UT 84103 USA. [Rodeberg, David] Univ Pittsburgh, Pittsburgh, PA USA. [Teot, Lisa] Dana Farber Canc Inst, Boston, MA 02115 USA. [Anderson, James] Univ Nebraska Med Ctr, Omaha, NE USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD NOV PY 2010 VL 55 IS 5 BP 902 EP 902 PG 1 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 663SN UT WOS:000282910200446 ER PT J AU Bauer, DE Schwartz, BE Hofer, M Cameron, MJ Grant, FD Rodriguez-Galindo, C Bradner, JE Sallan, SE French, CA AF Bauer, Daniel E. Schwartz, Brian E. Hofer, Matthias Cameron, Michael J. Grant, Frederick D. Rodriguez-Galindo, Carlos Bradner, James E. Sallan, Stephen E. French, Christopher A. TI RESPONSE OF NUT MIDLINE CARCINOMA TO HISTONE DEACETYLASE INHIBITION AND ESTABLISHMENT OF AN INTERNATIONAL REGISTRY SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Bauer, Daniel E.; Rodriguez-Galindo, Carlos; Bradner, James E.; Sallan, Stephen E.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Bauer, Daniel E.; Grant, Frederick D.] Childrens Hosp, Boston, MA 02115 USA. [Schwartz, Brian E.; Hofer, Matthias; French, Christopher A.] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD NOV PY 2010 VL 55 IS 5 BP 907 EP 907 PG 1 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 663SN UT WOS:000282910200465 ER PT J AU Chi, S Fisher, M Knipstein, J Fangusaro, J Zimmerman, MA Pietrantonio, J Kieran, M AF Chi, Susan Fisher, Michael Knipstein, Jeffrey Fangusaro, Jason Zimmerman, Mary Ann Pietrantonio, Jay Kieran, Mark TI AN INTENSIVE MULTIMODALITY APPROACH FOR PATIENTS WITH EXTRA-RENAL, EXTRACRANIAL MALIGNANT RHABDOID TUMORS SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Chi, Susan; Zimmerman, Mary Ann; Pietrantonio, Jay; Kieran, Mark] Dana Farber Canc Inst, Boston, MA 02115 USA. [Fisher, Michael] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Knipstein, Jeffrey] Childrens Hosp Denver CO, Denver, CO USA. [Fangusaro, Jason] Childrens Mem Hosp, Chicago, IL 60614 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD NOV PY 2010 VL 55 IS 5 BP 913 EP 913 PG 1 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 663SN UT WOS:000282910200487 ER PT J AU Kuhlthau, K MacDonald, S Rivera, D Tarbell, NJ Yock, T AF Kuhlthau, Karen MacDonald, Shannon Rivera, Dianali Tarbell, Nancy J. Yock, Torunn TI HEALTH-RELATED QUALITY OF LIFE OF PEDIATRIC BRAIN TUMOR PATIENTS ON PROTON TREATMENT SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Kuhlthau, Karen; MacDonald, Shannon; Rivera, Dianali; Tarbell, Nancy J.; Yock, Torunn] Massachusetts Gen Hosp, Ctr Child & Adolescent Hlth Policy, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD NOV PY 2010 VL 55 IS 5 BP 921 EP 921 PG 1 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 663SN UT WOS:000282910200516 ER PT J AU Chi, S Rodriguez, D Young-Poussaint, T Zimmerman, MA Marcus, K Goumnerova, L Ullrich, N Manley, P Kieran, M AF Chi, Susan Rodriguez, Diana Young-Poussaint, Tina Zimmerman, Mary Ann Marcus, Karen Goumnerova, Liliana Ullrich, Nicole Manley, Peter Kieran, Mark TI CT AND MRI FINDINGS OF CENTRAL NERVOUS SYSTEM ATYPICAL TERATOID RHABDOID TUMORS IN CHILDREN SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Chi, Susan; Zimmerman, Mary Ann; Manley, Peter; Kieran, Mark] Dana Farber Canc Inst, Boston, MA 02115 USA. [Rodriguez, Diana; Young-Poussaint, Tina; Marcus, Karen; Goumnerova, Liliana; Ullrich, Nicole] Childrens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD NOV PY 2010 VL 55 IS 5 BP 926 EP 927 PG 2 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 663SN UT WOS:000282910200536 ER PT J AU Bechard, L Feldman, H Venick, R Gura, K Guinan, E Duggan, C AF Bechard, Lori Feldman, Henry Venick, Robert Gura, Kathleen Guinan, Eva Duggan, Christopher TI RESTING ENERGY EXPENDITURE DECLINES IN CHILDREN FOLLOWING HEMATOPOIETIC STEM CELL TRANSPLANTATION SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Bechard, Lori] Childrens Hosp, Clin Nutr Serv, Boston, MA 02115 USA. [Feldman, Henry] Childrens Hosp, Clin Res Program, Boston, MA 02115 USA. [Venick, Robert] Univ Calif Los Angeles, Mattel Childrens Hosp, Los Angeles, CA USA. [Guinan, Eva] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD NOV PY 2010 VL 55 IS 5 BP 927 EP 928 PG 2 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 663SN UT WOS:000282910200540 ER PT J AU Daly, K Colan, S Blume, E Margossian, R Gauvreau, K Duncan, C Lehmann, L Chen, MH AF Daly, Kevin Colan, Steven Blume, Elizabeth Margossian, Renee Gauvreau, Kimberlee Duncan, Christine Lehmann, Leslie Chen, Ming Hui TI CHILDREN HAVE WORSENED ECHOCARDIOGRAPHIC MEASURES OF SYSTOLIC AND DIASTOLIC FUNCTION 1 YEAR AFTER HEMATOPOIETIC STEM CELL TRANSPLANTATION SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Daly, Kevin; Colan, Steven; Blume, Elizabeth; Margossian, Renee; Gauvreau, Kimberlee; Duncan, Christine; Lehmann, Leslie; Chen, Ming Hui] Childrens Hosp, Boston, MA 02115 USA. [Duncan, Christine; Lehmann, Leslie] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD NOV PY 2010 VL 55 IS 5 BP 944 EP 944 PG 1 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 663SN UT WOS:000282910200599 ER PT J AU Breyer, J AF Breyer, Joanna TI WHAT PARENTS FACE AS THEIR CHILD IS DYING AND THE ROLE OF CAREGIVERS SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Breyer, Joanna] Dana Farber Canc Inst, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD NOV PY 2010 VL 55 IS 5 BP 946 EP 946 PG 1 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 663SN UT WOS:000282910200607 ER PT J AU Eilegard, A Kreicbergs, U Steineck, G Friedrichdorf, S Osenga, K Nugent, A Dussel, V Wolfe, J AF Eilegard, Alexandra Kreicbergs, Ulrika Steineck, Gunnar Friedrichdorf, Stefan Osenga, Kasi Nugent, Andrea Dussel, Veronica Wolfe, Joanne TI SIBLINGS PERCEPTIONS ABOUT PARTICIPATION IN RESEARCH REGARDING THE LOSS OF A BROTHER OR SISTER TO CANCER SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Eilegard, Alexandra; Kreicbergs, Ulrika; Steineck, Gunnar] Karolinska Inst, Stockholm, Sweden. [Nugent, Andrea; Dussel, Veronica; Wolfe, Joanne] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD NOV PY 2010 VL 55 IS 5 BP 948 EP 948 PG 1 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 663SN UT WOS:000282910200612 ER PT J AU Ullrich, C Dussel, V Hilden, J Sheaffer, J Lehmann, L Wolfe, J AF Ullrich, Christina Dussel, Veronica Hilden, Joanne Sheaffer, Jan Lehmann, Leslie Wolfe, Joanne TI END-OF-LIFE EXPERIENCE OF CHILDREN UNDERGOING HEMATOPOIETIC STEM CELL TRANSPLANT FOR CANCER: PARENT AND PROVIDER PERSPECTIVES AND PATTERNS OF CARE SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Ullrich, Christina; Dussel, Veronica; Lehmann, Leslie; Wolfe, Joanne] Childrens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Hilden, Joanne] Peyton Manning Childrens Hosp St Vincent, Dept Pediat, Indianapolis, IN USA. [Sheaffer, Jan] Childrens Hosp & Clin Minnesota, Dept Pediat Hematol Oncol, Minneapolis, MN USA. NR 0 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 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD NOV PY 2010 VL 55 IS 5 BP 950 EP 950 PG 1 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 663SN UT WOS:000282910200622 ER PT J AU Sulis, ML Foca, M Silverman, L Kelly, K AF Sulis, Maria Luisa Foca, Marc Silverman, Lewis Kelly, Kara TI INFECTION CONTROL PRACTICES DURING INDUCTION CHEMOTHERAPY FOR ACUTE LYMPHOBLASTIC LEUKEMIA: RESULTS OF A SURVEY FROM THE DANA-FARBER CANCER INSTITUTE ALL CONSORTIUM SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Sulis, Maria Luisa; Foca, Marc; Kelly, Kara] Columbia Univ, New York, NY USA. [Silverman, Lewis] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD NOV PY 2010 VL 55 IS 5 BP 956 EP 956 PG 1 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 663SN UT WOS:000282910200644 ER PT J AU Brinkman, T Delaney, B Manley, P Muriel, A Chordas, C Liptak, C AF Brinkman, Tara Delaney, Brian Manley, Peter Muriel, Anna Chordas, Christine Liptak, Cori TI SUICIDAL IDEATION IN SURVIVORS OF PEDIATRIC BRAIN TUMORS SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Brinkman, Tara; Delaney, Brian; Manley, Peter; Muriel, Anna; Chordas, Christine; Liptak, Cori] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 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 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD NOV PY 2010 VL 55 IS 5 BP 957 EP 958 PG 2 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 663SN UT WOS:000282910200648 ER PT J AU Liptak, C Zwemer, E Merport, A Manley, P Recklitis, C AF Liptak, Cori Zwemer, Eric Merport, Anna Manley, Peter Recklitis, Christopher TI COMPARING PARENT AND SURVIVOR SELF-REPORT OF PSYCHOLOGICAL DISTRESS IN ADOLESCENT AND YOUNG ADULT BRAIN TUMOR SURVIVORS: RESULTS FROM PROJECT REACH SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Liptak, Cori; Manley, Peter] Harvard Univ, Sch Med, Dana Farber Canc Inst, Neurooncol Outcomes Clin, Boston, MA 02115 USA. [Zwemer, Eric; Recklitis, Christopher] Harvard Univ, Sch Med, Dana Farber Canc Inst, Perini Family Survivors Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD NOV PY 2010 VL 55 IS 5 BP 962 EP 963 PG 2 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 663SN UT WOS:000282910200666 ER PT J AU Zwemer, E Mahler, H Werchniak, A Recklitis, C AF Zwemer, Eric Mahler, Heike Werchniak, Andrew Recklitis, Christopher TI SUN EXPOSURE IN CANCER SURVIVORS ON AND OFF THE BEACH: RESULTS FROM PROJECT REACH SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Mahler, Heike] Univ Calif San Diego, La Jolla, CA 92093 USA. [Werchniak, Andrew] Harvard Univ, Brigham & Womens Hosp, Dana Farber Canc Inst, Sch Med, Boston, MA 02115 USA. [Recklitis, Christopher] Harvard Univ, Sch Med, Dana Farber Canc Inst, Perini Family Survivors Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD NOV PY 2010 VL 55 IS 5 BP 962 EP 962 PG 1 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 663SN UT WOS:000282910200663 ER PT J AU Bober, S Merport, A Nancarrow, CM Diller, L Recklitis, C AF Bober, Sharon Merport, Anna Nancarrow, Cheryl Medeiros Diller, Lisa Recklitis, Christopher TI SEXUAL FUNCTION IN CHILDHOOD CANCER SURVIVORS: RESULTS FROM PROJECT REACH SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Diller, Lisa; Recklitis, Christopher] Harvard Univ, Sch Med, Dana Farber Canc Inst, Perini Family Survivors Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD NOV PY 2010 VL 55 IS 5 BP 963 EP 963 PG 1 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 663SN UT WOS:000282910200668 ER PT J AU Casey, R Zwemer, E Recklitis, C AF Casey, Robert Zwemer, Eric Recklitis, Christopher TI IS SURVIVOR IDENTITY ASSOCIATED WITH PHYSICAL AND BEHAVIORAL HEALTH?: RESULTS FROM PROJECT REACH SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Zwemer, Eric; Recklitis, Christopher] Harvard Univ, Sch Med, Dana Farber Canc Inst, Perini Family Survivors Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD NOV PY 2010 VL 55 IS 5 BP 963 EP 963 PG 1 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 663SN UT WOS:000282910200667 ER PT J AU Chordas, C Manley, P Nancarrow, CM Merport, A Zwemer, E Liptak, C Recklitis, C AF Chordas, Christine Manley, Peter Nancarrow, Cheryl Medeiros Merport, Anna Zwemer, Eric Liptak, Cori Recklitis, Christopher TI PREVALENCE OF AND FACTORS ASSOCIATED WITH POST-CANCER PAIN IN CHILDHOOD BRAIN TUMOR SURVIVORS: RESULTS FROM PROJECT REACH SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Manley, Peter; Liptak, Cori] Harvard Univ, Sch Med, Dana Farber Canc Inst, Neurooncol Outcomes Clin, Boston, MA 02115 USA. [Zwemer, Eric; Recklitis, Christopher] Harvard Univ, Sch Med, Dana Farber Canc Inst, Perini Family Survivors Ctr, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD NOV PY 2010 VL 55 IS 5 BP 963 EP 963 PG 1 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 663SN UT WOS:000282910200669 ER PT J AU Lind, ED Kenney, L Vrooman, L Recklitis, C Diller, L AF Lind, Eileen Duffey Kenney, Lisa Vrooman, Linda Recklitis, Christopher Diller, Lisa TI ASSESSING THE UTILITY OF A TRANSITION PROGRAM: A SURVEY OF PARENT PARTICIPANTS SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Kenney, Lisa; Vrooman, Linda; Recklitis, Christopher; Diller, Lisa] DFCI, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD NOV PY 2010 VL 55 IS 5 BP 974 EP 974 PG 1 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 663SN UT WOS:000282910200708 ER PT J AU Aristizabal, P Day, S Velez, G Rivera, G Rodriguez-Galindo, C Ribeiro, R Roberts, W AF Aristizabal, Paula Day, Sara Velez, George Rivera, Gaston Rodriguez-Galindo, Carlos Ribeiro, Raul Roberts, William TI A NOVEL MODEL OF TWINNING: OUTREACH PROGRAMS IN THE BORDER REGION SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Aristizabal, Paula] Rady Childrens Hosp San Diego, San Diego, CA USA. [Day, Sara; Velez, George; Rivera, Gaston; Ribeiro, Raul] St Jude Childrens Hosp, Int Outreach Program, Memphis, TN 38105 USA. [Rodriguez-Galindo, Carlos] Dana Farber Canc Inst, Boston, MA 02115 USA. [Roberts, William] Univ Calif San Diego, Rady Childrens Hosp San Diego, San Diego, CA 92103 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD NOV PY 2010 VL 55 IS 5 BP 976 EP 977 PG 2 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 663SN UT WOS:000282910200717 ER PT J AU Deady, A Androkites, A Frederick, E AF Deady, Ann Androkites, Arlene Frederick, Elisa TI IDENTIFICATION AND MANAGEMENT OF THROMBOSIS IN PEDIATRIC PATIENTS WITH ACUTE LYMPHOBLASTIC LEUKEMIA RECEIVING ASPARAGINASE THERAPY AT DANA-FARBER CANCER INSTITUTE SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Deady, Ann; Androkites, Arlene; Frederick, Elisa] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD NOV PY 2010 VL 55 IS 5 BP 984 EP 984 PG 1 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 663SN UT WOS:000282910200748 ER PT J AU OBrien-Shea, J Bennett, J Byrne, K Federico, A Dinning, C Hussey, N Ronan, J Spidle, J Strykowski, J Shusterman, S AF OBrien-Shea, Joan Bennett, James Byrne, Kathleen Federico, Amy Dinning, Connie Hussey, Nora Ronan, Joan Spidle, Jennifer Strykowski, Jennifer Shusterman, Suzanne TI A MULTIDISCIPLINARY APPROACH TO IMPLEMENTING PEDIATRIC ONCOLOGY CLINICAL TRIALS SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [OBrien-Shea, Joan; Byrne, Kathleen] Childrens Hosp, Boston, MA 02115 USA. [Bennett, James; Federico, Amy; Dinning, Connie] Dana Faber Childrens Hosp Canc Care, Boston, MA USA. [Hussey, Nora] Dana Farber Canc Inst, Boston, MA 02115 USA. [Ronan, Joan; Spidle, Jennifer; Strykowski, Jennifer; Shusterman, Suzanne] Dana Farber Childrens Hosp Canc Care, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD NOV PY 2010 VL 55 IS 5 BP 986 EP 987 PG 2 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 663SN UT WOS:000282910200756 ER PT J AU Comeau, M Temple, K Costello, C AF Comeau, Michael Temple, Kendal Costello, Caroline TI HEMATOPOIETIC STEM CELL TRANSPLANT DISCHARGE: WHAT IS THE BEST PRACTICE FOR TRANSITIONING TO THE OUTPATIENT SETTING? SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Comeau, Michael] Dana Farber Canc Inst, Boston, MA 02115 USA. [Costello, Caroline] Childrens Hosp, HSCT, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD NOV PY 2010 VL 55 IS 5 BP 988 EP 989 PG 2 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 663SN UT WOS:000282910200764 ER PT J AU Federico, A Spidle, J Ronan, J Byrne, K Hussey, N Shusterman, S AF Federico, Amy Spidle, Jennifer Ronan, Joan Byrne, Kathleen Hussey, Nora Shusterman, Suzanne TI DEVELOPMENT OF PROVIDER TOOLS TO IMPROVE THE PROCESS OF RESEARCH IMPLEMENTATION: HIGH RISK NEUROBLASTOMA PROTOCOL ANBL0032 SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 [Federico, Amy; Spidle, Jennifer; Ronan, Joan; Hussey, Nora; Shusterman, Suzanne] Childrens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD NOV PY 2010 VL 55 IS 5 BP 988 EP 988 PG 1 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 663SN UT WOS:000282910200763 ER PT J AU Mukherjee, R McQuinn, TC Dugan, MA Saul, JP Spinale, FG AF Mukherjee, Rupak McQuinn, Tim C. Dugan, Melissa A. Saul, J. Philip Spinale, Francis G. TI Cardiac Function and Circulating Cytokines After Endotoxin Exposure in Neonatal Mice SO PEDIATRIC RESEARCH LA English DT Article ID FLOW CARDIOPULMONARY BYPASS; ARTERIAL SWITCH OPERATION; INDUCED ORGAN DAMAGE; N-ACETYLCYSTEINE; OXIDATIVE STRESS; INFLAMMATORY RESPONSE; CARDIOPLEGIC ARREST; INNATE IMMUNITY; CONSCIOUS RATS; SHOCK AB Complications after cardiac surgery in neonates can occur because of activation of the inflammatory system. This study used lipopolysaccharide (LPS) endotoxin exposure to cause cytokine activation in neonatal mice and examine left ventricular (LV) function and the effects of antioxidant treatment on cytokine levels. Neonatal mice (6 d old) were injected with either 25 mg/kg LPS (n = 13) or PBS (n = 14), and LV function (echocardiography) was measured at 4 h. Plasma levels of TNF-alpha, IL-4, IL-6, and IL-10 were measured at 30 min, I, 2, and 4 h after injection (a = 5 mice per group). Effects of pretreatment with N-acetylcysteine (NAC, 50 mg/kg) on cytokine levels were examined at 2 and 4 h after PBS or LPS (n = 5 mice per group). Four hours after LPS, heart rate was increased (434 +/- 14 versus 405 +/- 14 bpm, p < 0.05). LV end-diastolic dimension and ejection time were reduced with LPS (both p < 0.05). LPS exposure increased plasma TNF-alpha IL-6, and IL-10 levels. NAC pretreatment attenuated the increases in TNF-alpha and IL-6 levels, but augmented IL-10 levels at 2 h post-LPS. LPS exposure altered cardiac performance and activated cytokines in neonatal mice, which may be ameliorated using antioxidants. (Pediatr Res 68: 381-386, 2010) C1 [Mukherjee, Rupak; Spinale, Francis G.] Med Univ S Carolina, Div Cardiothorac Surg, Charleston, SC 29425 USA. [Mukherjee, Rupak; McQuinn, Tim C.; Dugan, Melissa A.; Saul, J. Philip] Med Univ S Carolina, Div Pediat Cardiol, Charleston, SC 29425 USA. [Spinale, Francis G.] Ralph H Johnson VA Med Ctr, Charleston, SC 29401 USA. RP Mukherjee, R (reprint author), Med Univ S Carolina, Div Cardiothorac Surg, Strom Thurmond Res Bldg,770 MUSC Complex,Suite 62, Charleston, SC 29425 USA. EM mukherr@musc.edu FU National Heart, Lung, and Blood Institute [HL-45024, HL-97012, PO1-48788]; VA; Division of Pediatric Cardiology FX Supported, in part, by Grants HL-45024, HL-97012, and PO1-48788 from National Heart, Lung, and Blood Institute, a VA Merit Award [to F.G.S.], and departmental funds from the Division of Pediatric Cardiology. NR 40 TC 9 Z9 10 U1 0 U2 1 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 2010 VL 68 IS 5 BP 381 EP 386 PG 6 WC Pediatrics SC Pediatrics GA 670GR UT WOS:000283409700003 PM 20613681 ER PT J AU Atochin, DN Huang, PL AF Atochin, Dmitriy N. Huang, Paul L. TI Endothelial nitric oxide synthase transgenic models of endothelial dysfunction SO PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY LA English DT Review DE Nitric oxide; Endothelium; Vascular dysfunction; Transgenic mouse; Cerebral circulation ID ISCHEMIC-HEART-DISEASE; BROWN ADIPOSE-TISSUE; E-DEFICIENT MICE; INSULIN-RESISTANCE; METABOLIC SYNDROME; L-ARGININE; KNOCKOUT MICE; MICROVASCULAR DYSFUNCTION; MYOCARDIAL-INFARCTION; CARDIOVASCULAR RISK AB Endothelial production of nitric oxide is critical to the regulation of vascular responses, including vascular tone and regional blood flow, leukocyte-endothelial interactions, platelet adhesion and aggregation, and vascular smooth muscle cell proliferation. A relative deficiency in the amount of bioavailable vascular NO results in endothelial dysfunction, with conditions that are conducive to the development of atherosclerosis: thrombosis, inflammation, neointimal proliferation, and vasoconstriction. This review focuses on mouse models of endothelial dysfunction caused by direct genetic modification of the endothelial nitric oxide synthase (eNOS) gene. We first describe the cardiovascular phenotypes of eNOS knockout mice, which are a model of total eNOS gene deficiency and thus the ultimate model of endothelial dysfunction. We then describe S1177A and S1177D eNOS mutant mice as mouse models with altered eNOS phosphorylation and therefore varying degrees of endothelial dysfunction. These include transgenic mice that carry the eNOS S1177A and S1177D transgenes, as well as knockin mice in which the endogenous eNOS gene has been mutated to carry the S1177A and S1177D mutations. Together, eNOS knockout mice and eNOS S1177 mutant mice are useful tools to study the effects of total genetic deficiency of eNOS as well as varying degrees of endothelial dysfunction caused by eNOS S1177 phosphorylation. C1 [Huang, Paul L.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Charlestown, MA 02129 USA. [Atochin, Dmitriy N.; Huang, Paul L.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Atochin, Dmitriy N.; Huang, Paul L.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. [Atochin, Dmitriy N.; Huang, Paul L.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Huang, PL (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, 149 13th St, Charlestown, MA 02129 USA. EM phuang1@partners.org RI Atochin, Dmitriy/Q-3150-2016 FU NINDS NIH HHS [R01 NS033335] NR 88 TC 54 Z9 59 U1 1 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0031-6768 J9 PFLUG ARCH EUR J PHY JI Pflugers Arch. PD NOV PY 2010 VL 460 IS 6 BP 965 EP 974 DI 10.1007/s00424-010-0867-4 PG 10 WC Physiology SC Physiology GA 666NS UT WOS:000283122700003 PM 20697735 ER PT J AU Figlewicz, DP Sipols, AJ AF Figlewicz, Dianne P. Sipols, Alfred J. TI Energy regulatory signals and food reward SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Review DE Insulin; Leptin; Ghrelin; Motivation; Food intake; Reward; Dopamine ID VENTRAL TEGMENTAL AREA; BLOOD-BRAIN-BARRIER; MELANIN-CONCENTRATING HORMONE; HYPOTHALAMIC NEUROPEPTIDE-Y; CENTRAL-NERVOUS-SYSTEM; HIGH-FAT DIET; LEPTIN-RESPONSIVE NEURONS; OPIOID RECEPTOR-BINDING; NUCLEUS-ACCUMBENS SHELL; AGOUTI-RELATED PEPTIDE AB The hormones insulin leptin and ghrelin have been demonstrated to act in the central nervous system (CNS) as regulators of energy homeostasis acting at medial hypothalamic sites Here we summarize research demonstrating that in addition to direct homeostatic actions at the hypothalamus CNS circuitry that subserves reward and is also a direct and indirect target for the action of these endocrine regulator, of energy homeostasis Specifically insulin and leptin can decrease food reward behaviors and modulate the function of neurotransmitter systems and neural circuitry that mediate food reward the midbrain dopamine (DA) and opioidergic pathways Ghrelin can increase food reward behaviors and support midbrain DA neuronal function We summarize discussion of behavioral systems and cellular evidence in support of the contributions of reward circuitry to the homeostatic roles of these hormones in the CNS The understanding of neuroendocrine modulation of food reward as well as food reward modulation by diet and obesity may point to new directions for therapeutic approaches to overeating or eating disorders Published by Elsevier Inc C1 [Figlewicz, Dianne P.] VA Puget Sound Hlth Care Syst, Seattle Div, Seattle, WA 98108 USA. [Figlewicz, Dianne P.] Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. [Sipols, Alfred J.] Univ Latvia, Fac Med, LV-1586 Riga, Latvia. [Sipols, Alfred J.] Univ Latvia, Inst Expt & Clin Med, LV-1586 Riga, Latvia. RP Figlewicz, DP (reprint author), VA Puget Sound Hlth Care Syst, Seattle Div, 1660 S Columbian Way, Seattle, WA 98108 USA. FU Dept of Veterans Affairs; NIH [DK40963]; University of Latvia [Y2-ZP84-003] FX This work is supported by a Career Scientist Award from the Dept of Veterans Affairs and NIH Grant DK40963 (DPF) and a University of Latvia Grant Y2-ZP84-003 (AJS) NR 249 TC 63 Z9 64 U1 3 U2 16 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD NOV PY 2010 VL 97 IS 1 SI SI BP 15 EP 24 DI 10.1016/j.pbb.2010.03.002 PG 10 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 689YA UT WOS:000284965800003 PM 20230849 ER PT J AU Geisler, T Gawaz, M Steinhubl, SR Bhatt, DL Storey, RF Flather, M AF Geisler, Tobias Gawaz, Meinrad Steinhubl, Steven R. Bhatt, Deepak L. Storey, Robert F. Flather, Marcus TI Current strategies in antiplatelet therapy - Does identification of risk and adjustment of therapy contribute to more effective, personalized medicine in cardiovascular disease? (vol 127, pg 95, 2010) SO PHARMACOLOGY & THERAPEUTICS LA English DT Correction C1 [Geisler, Tobias; Flather, Marcus] Royal Brompton & Harefield NHS Fdn Trust, Clin Trials & Evaluat Unit, London SW3 6NP, England. [Geisler, Tobias; Gawaz, Meinrad] Univ Tubingen, Med Klin 3, Univ Klinikum, Tubingen, Germany. [Steinhubl, Steven R.] Switzerland & Ceisinger Clin, Danville, PA USA. [Steinhubl, Steven R.] Med Co, CH-8058 Zurich, Switzerland. [Bhatt, Deepak L.] Brigham & Womens Hosp, VA Boston Healthcare Syst, Boston, MA 02115 USA. [Bhatt, Deepak L.] Harvard Univ, Sch Med, Boston, MA USA. [Storey, Robert F.] Univ Sheffield, Dept Cardiovasc Sci, Sheffield, S Yorkshire, England. RP Geisler, T (reprint author), Royal Brompton & Harefield NHS Fdn Trust, Clin Trials & Evaluat Unit, Sydney St, London SW3 6NP, England. NR 1 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 0163-7258 J9 PHARMACOL THERAPEUT JI Pharmacol. Ther. PD NOV PY 2010 VL 128 IS 2 BP 385 EP 385 DI 10.1016/j.pharmthera.2010.07.002 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 670FP UT WOS:000283406900008 ER PT J AU Sallum, UW Zheng, X Verma, S Hasan, T AF Sallum, Ulysses W. Zheng, Xiang Verma, Sarika Hasan, Tayyaba TI Rapid Functional Definition of Extended Spectrum beta-Lactamase Activity in Bacterial Cultures via Competitive Inhibition of Fluorescent Substrate Cleavage SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID KLEBSIELLA-PNEUMONIAE; RESISTANCE; CEFTAZIDIME; GENES; SEQUENCES AB The functional definition of extended-spectrum beta-lactamase (ESBL) activity is a clinical challenge. Here we report a rapid and convenient assay of beta-lactamase activity through the competitive inhibition of fluorescent substrate hydrolysis that provides a read-out nearly 40x more rapidly than conventional techniques for functional definition. A panel of beta-lactam antibiotics was used for competition against beta-lactamase enzyme-activated photosensitizer (beta-LEAP) yielding a competitive index (C(i)) in 30 min. Significant differences in the relative C(i) values of the panel of beta-lactams were determined in vitro for Bacillus cereus penicillinase. Additionally, the relative C(i) values for whole bacterial cell suspensions of B. cereus 5/beta were compared with the relative minimal inhibitory concentration (MIC) values and a correlation coefficient of 0.899 was determined. We further demonstrated the ability of beta-LEAP to probe the capacity of ceftazidime to inhibit the enzyme activity of a panel of ESBL-producing Escherichia coli. The bacteria were assayed for susceptibility to ceftazidime and the relative MIC values were compared with the relative C(i) values for ceftazidime yielding a correlation coefficient of 0.984. This work demonstrates for the first time the whole cell assay of the competitive inhibition of beta-lactamase enzyme activity and derivation of associated constants. C1 [Sallum, Ulysses W.; Zheng, Xiang; Verma, Sarika; Hasan, Tayyaba] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02163 USA. RP Hasan, T (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wellman Ctr Photomed, Boston, MA 02163 USA. EM thasan@partners.org FU U.S. Department of Defense [FA955-04-1-0079]; Bill and Melinda Gates Foundation [51813]; National Institutes of Health [AR007098-35] FX Supported by funding from the U.S. Department of Defense (FA955-04-1-0079); the Bill and Melinda Gates Foundation (51813) and the National Institutes of Health (AR007098-35). NR 17 TC 3 Z9 3 U1 0 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD NOV-DEC PY 2010 VL 86 IS 6 BP 1267 EP 1271 DI 10.1111/j.1751-1097.2010.00801.x PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 682UW UT WOS:000284429500015 PM 20854415 ER PT J AU Kishen, A Upadya, M Tegos, GP Hamblin, MR AF Kishen, Anil Upadya, Megha Tegos, George P. Hamblin, Michael R. TI Efflux Pump Inhibitor Potentiates Antimicrobial Photodynamic Inactivation of Enterococcus faecalis Biofilm SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID MULTIDRUG-RESISTANCE; SURFACE PROTEIN; IN-VITRO; THERAPY; INFECTION; ESP; SUSCEPTIBILITY; CIPROFLOXACIN; DISINFECTION; ENDOCARDITIS AB Microbial biofilm architecture contains numerous protective features, including extracellular polymeric material that render biofilms impermeable to conventional antimicrobial agents. This study evaluated the efficacy of antimicrobial photodynamic inactivation (aPDI) of Enterococcus faecalis biofilms. The ability of a cationic, phenothiazinium photosensitizer, methylene blue (MB) and an anionic, xanthene photosensitizer, rose bengal (RB) to inactivate biofilms of E. faecalis (OG1RF and FA 2-2) and disrupt the biofilm structure was evaluated. Bacterial cells were tested as planktonic suspensions, intact biofilms and biofilm-derived suspensions obtained by the mechanical disruption of biofilms. The role of a specific microbial efflux pump inhibitor (EPI), verapamil hydrochloride in the MB-mediated aPDI of E. faecalis biofilms was also investigated. The results showed that E. faecalis biofilms exhibited significantly higher resistance to aPDI when compared with E. faecalis in suspension (P < 0.001). aPDI with cationic MB produced superior inactivation of E. faecalis strains in a biofilm along with significant destruction of biofilm structure when compared with anionic RB (P < 0.05). The ability to inactivate biofilm bacteria was further enhanced when the EPI was used with MB (P < 0.001). These experiments demonstrated the advantage of a cationic phenothiazinium photosensitizer combined with an EPI to inactivate biofilm bacteria and disrupt biofilm structure. C1 [Kishen, Anil; Tegos, George P.; Hamblin, Michael R.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. [Kishen, Anil] Univ Toronto, Fac Dent, Toronto, ON, Canada. [Upadya, Megha] Natl Univ Singapore, Fac Dent, Singapore 117548, Singapore. [Tegos, George P.; Hamblin, Michael R.] Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. [Hamblin, Michael R.] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Hamblin, MR (reprint author), Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. EM hamblin@helix.mgh.harvard.edu RI Tegos, George/C-8830-2011; Upadya, Megha/N-2235-2016; OI Hamblin, Michael/0000-0001-6431-4605 FU National Institute of Allergy and Infectious Disease [AI050875]; Department of Restorative Dentistry, National University of Singapore; National University of Singapore [R-224-000-024-112] FX This work was supported by the National Institute of Allergy and Infectious Disease (grant AI050875 to MRH). The authors are grateful to Eleutherios Mylonakis (Massachusetts General Hospital, Boston, MA), Frank Stermitz (Colorado State University, Fort Collins, CO) and Fred Ausebel (Massachusetts General Hospital, Boston, MA). The support from the Department of Restorative Dentistry, National University of Singapore and the funding from the National University of Singapore ARF Grant R-224-000-024-112 are gratefully acknowledged. NR 52 TC 37 Z9 38 U1 0 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD NOV-DEC PY 2010 VL 86 IS 6 BP 1343 EP 1349 DI 10.1111/j.1751-1097.2010.00792.x PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 682UW UT WOS:000284429500024 PM 20860692 ER PT J AU Vora, AJ Doerr, KD Wolfer, LR AF Vora, Ariana J. Doerr, Katherine D. Wolfer, Lee R. TI Functional Anatomy and Pathophysiology of Axial Low Back Pain: Disc, Posterior Elements, Sacroiliac Joint, and Associated Pain Generators SO PHYSICAL MEDICINE AND REHABILITATION CLINICS OF NORTH AMERICA LA English DT Article DE Low back pain; Tensegrity; Ligament; Fascia; Anatomy; Disc; Zygapophysial joint ID MYOFASCIAL FORCE TRANSMISSION; LUMBAR INTERVERTEBRAL DISC; TUMOR-NECROSIS-FACTOR; ILIOLUMBAR LIGAMENT; FACET JOINT; MAGNETIC-RESONANCE; THORACOLUMBAR FASCIA; ZYGAPOPHYSIAL JOINT; SACROTUBEROUS LIGAMENT; INTERSPINOUS LIGAMENT AB Careful consideration of functional lumbosacral anatomy reveals the capacity for pain generation in the disc zygapophysial joint sacroiliac joint and surrounding ligaments However the methods used to definitively implicate a particular anatomic structure in axial low back pain have limitations Anatomically and biomechanically the discs and poste nor elements are inextricably connected to a dynamic biotensegrity net work of ligaments muscles and fascia This article examines key lumbosacral anatomic structures and their functional interdependence at the macroscopic microscopic and biomechanical level Particular attention is given to the capacity of each structure to generate low back pain C1 [Vora, Ariana J.; Doerr, Katherine D.] Harvard Univ, Dept Phys Med & Rehabil, Sch Med, Boston, MA 02144 USA. [Vora, Ariana J.] Massachusetts Gen Hosp Phys Med & Rehabil, Boston, MA 02144 USA. [Vora, Ariana J.; Doerr, Katherine D.] Spaulding Rehabil Hosp, Boston, MA 02144 USA. [Wolfer, Lee R.] Spinal Diagnost & Treatment Ctr, Daly City, CA 94015 USA. RP Vora, AJ (reprint author), Harvard Univ, Dept Phys Med & Rehabil, Massachusetts Gen Hosp, Sch Med, 5 Longfellow Pl,Suite 201, Boston, MA 02144 USA. NR 170 TC 8 Z9 11 U1 1 U2 8 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1047-9651 J9 PHYS MED REH CLIN N JI Phys. Med. Rehabil. Clin. N. Am. PD NOV PY 2010 VL 21 IS 4 BP 679 EP + DI 10.1016/j.pmr.2010.07.005 PG 32 WC Rehabilitation SC Rehabilitation GA 687PJ UT WOS:000284790100004 PM 20977956 ER PT J AU Lee, TJ AF Lee, Timothy J. TI Pharmacologic Treatment for Low Back Pain: One Component of Pain Care SO PHYSICAL MEDICINE AND REHABILITATION CLINICS OF NORTH AMERICA LA English DT Article DE Low back pain; Acetaminophen; Nonsteroidal anti-inflammatory drugs; Muscle relaxants; Antidepressants; Antiepileptics; Opioids ID OPIOID PRESCRIPTIONS; PROGNOSIS; THERAPY; TRIAL; COST AB Analgesic medications are commonly used for low back pain (LBP) Evidence on the efficacy of pharmacologic therapy for LBP comes from clinical trials that have many limitations including short-term studies and selective trial populations Evidence currently supports the use of short-term pharmacologic treatment for LBP However the safety and efficacy of long-term pharmacologic therapy for LBP is uncertain and therefore best used with caution monitoring and as one component of a comprehensive paincare approach emphasizing rehabilitation C1 VA Puget Sound, Seattle, WA 98108 USA. RP Lee, TJ (reprint author), VA Puget Sound, 1660 S Columbian Way, Seattle, WA 98108 USA. NR 20 TC 5 Z9 5 U1 1 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 1047-9651 J9 PHYS MED REH CLIN N JI Phys. Med. Rehabil. Clin. N. Am. PD NOV PY 2010 VL 21 IS 4 BP 793 EP + DI 10.1016/j.pmr.2010.06.013 PG 9 WC Rehabilitation SC Rehabilitation GA 687PJ UT WOS:000284790100009 PM 20977961 ER PT J AU Stout, A AF Stout, Alison TI Interventions for Low Back Pain Conclusions SO PHYSICAL MEDICINE AND REHABILITATION CLINICS OF NORTH AMERICA LA English DT Editorial Material C1 [Stout, Alison] Univ Washington, Dept Rehabil, Spine & Musculoskeletal Med Rehabil Care Serv, Vet Adm Puget Sound, Seattle, WA 98195 USA. [Stout, Alison] VA Puget Sound HCS, Dept Rehabil, Seattle, WA 98108 USA. RP Stout, A (reprint author), Univ Washington, Dept Rehabil, Spine & Musculoskeletal Med Rehabil Care Serv, Vet Adm Puget Sound, Seattle, WA 98195 USA. NR 1 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 1047-9651 J9 PHYS MED REH CLIN N JI Phys. Med. Rehabil. Clin. N. Am. PD NOV PY 2010 VL 21 IS 4 BP 817 EP 817 DI 10.1016/j.pmr.2010.08.003 PG 1 WC Rehabilitation SC Rehabilitation GA 687PJ UT WOS:000284790100011 PM 20977963 ER PT J AU Stout, A AF Stout, Alison TI Epidural Steroid Injections for Low Back Pain SO PHYSICAL MEDICINE AND REHABILITATION CLINICS OF NORTH AMERICA LA English DT Article DE Epidural steroid; Spine intervention; Lumbar; Transforaminal; Interlaminar; Caudal; Low back pain; Low back pain treatment ID SPINAL STENOSIS; RADICULAR PAIN; LUMBOSACRAL RADICULOPATHY; NITRIC-OXIDE; DOUBLE-BLIND; SCIATICA; INTERLAMINAR; EFFICACY; DISC; HERNIATIONS AB Epidural steroid injection (ESI) has been used as a treatment for low back pain for over 50 years In the last 10 to 15 years, there has been a significant increase in the use of ESIs for the treatment of low back pain and radicular pain without clear improvements in outcomes Recent literature has focused on the use of ESIs as treatment for radicular pain associated with low back pain with some studies showing benefit over control groups for limb symptoms There is a lack of literature, however, to support the use of ESIs for the treatment of axial low back pain The theoretical basis for their use technical considerations and the literature available for different approaches of access to the epidural space as pertaining to the treatment for low back pain without radiculopathy are reviewed C1 [Stout, Alison] Univ Washington, Dept Rehabil, Seattle, WA 98195 USA. RP Stout, A (reprint author), VA Puget Sound HCS, Rehabil Care Serv, 117 RCS,1660 S Columbian Way, Seattle, WA 98108 USA. NR 51 TC 10 Z9 12 U1 0 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 1047-9651 J9 PHYS MED REH CLIN N JI Phys. Med. Rehabil. Clin. N. Am. PD NOV PY 2010 VL 21 IS 4 BP 825 EP + DI 10.1016/j.pmr.2010.08.001 PG 11 WC Rehabilitation SC Rehabilitation GA 687PJ UT WOS:000284790100013 PM 20977965 ER PT J AU Stout, A AF Stout, Alison TI Discography SO PHYSICAL MEDICINE AND REHABILITATION CLINICS OF NORTH AMERICA LA English DT Article DE Discography; Spine intervention; Lumbar disc; Low back pain; Low back pain treatment ID LOW-BACK-PAIN; LUMBAR DISCOGRAPHY; ASYMPTOMATIC SUBJECTS; PROVOCATIVE DISCOGRAPHY; INTERVERTEBRAL DISC; SYMPTOMS; SPINE; DEGENERATION; FUSION; RATES AB Discography is a purely diagnostic interventional procedure performed to confirm or refute the hypothesis that a specific lumbar disc is the predominant source of a patient's low back pain In patients with severe low back pain, unresponsive to conservative care discography is used when clinical evaluation suggests that the pain is emanating from the intervertebral disc and other sources of pain have been ruled out The evidence for its use remains controversial There is variability and subjectivity in discography techniques and diagnostic criteria making some investigators question its validity When standardized diagnostic criteria are used, however, the specificity of discography improves dramatically Recently long-term side effects have been studied and lumbar discography seems to increase disc degeneration and herniation as detected on magnetic resonance imaging Although the clinical significance is unclear it is an important risk to consider prior to performing discography and changes in discography techniques may be indicated Discography remains the only technique, however that can be used to determine whether a patient's low back pain is emanating from the intervertebral disc and is a valid test when coupled with careful patient selection strict adherence to standardized technique and diagnostic criteria and consideration of possible long-term sequelae C1 [Stout, Alison] Vet Affairs Puget Sound Hlth Care Syst, Dept Rehabil, Rehabil Care Serv, Seattle, WA 98108 USA. [Stout, Alison] Univ Washington, Dept Rehabil, Seattle, WA 98195 USA. [Stout, Alison] Univ Washington, Spine & Musculoskeletal Med Rehabil Care Serv, Vet Adm Puget Sound, Dept Rehabil, Seattle, WA 98195 USA. RP Stout, A (reprint author), Vet Affairs Puget Sound Hlth Care Syst, Dept Rehabil, Rehabil Care Serv, 117 RCS,1660 S Columbian Way, Seattle, WA 98108 USA. NR 29 TC 7 Z9 8 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 1047-9651 J9 PHYS MED REH CLIN N JI Phys. Med. Rehabil. Clin. N. Am. PD NOV PY 2010 VL 21 IS 4 BP 859 EP + DI 10.1016/j.pmr.2010.07.002 PG 10 WC Rehabilitation SC Rehabilitation GA 687PJ UT WOS:000284790100017 PM 20977969 ER PT J AU Pomerantz, MM Shrestha, Y Flavin, RJ Regan, MM Penney, KL Mucci, LA Stampfer, MJ Hunter, DJ Chanock, SJ Schafer, EJ Chan, JA Tabernero, J Baselga, J Richardson, AL Loda, M Oh, WK Kantoff, PW Hahn, WC Freedman, ML AF Pomerantz, Mark M. Shrestha, Yashaswi Flavin, Richard J. Regan, Meredith M. Penney, Kathryn L. Mucci, Lorelei A. Stampfer, Meir J. Hunter, David J. Chanock, Stephen J. Schafer, Eric J. Chan, Jennifer A. Tabernero, Josep Baselga, Jose Richardson, Andrea L. Loda, Massimo Oh, William K. Kantoff, Philip W. Hahn, William C. Freedman, Matthew L. TI Analysis of the 10q11 Cancer Risk Locus Implicates MSMB and NCOA4 in Human Prostate Tumorigenesis SO PLOS GENETICS LA English DT Article ID GENOME-WIDE ASSOCIATION; HUMAN GENE-EXPRESSION; FUNCTIONAL-ANALYSIS; COLORECTAL-CANCER; SECRETORY PROTEIN; EPITHELIAL-CELLS; FAMILY-HISTORY; NUDE MICE; MULTIPLE; SUSCEPTIBILITY AB Genome-wide association studies (GWAS) have established a variant, rs10993994, on chromosome 10q11 as being associated with prostate cancer risk. Since the variant is located outside of a protein-coding region, the target genes driving tumorigenesis are not readily apparent. Two genes nearest to this variant, MSMB and NCOA4, are strong candidates for mediating the effects of rs109939934. In a cohort of 180 individuals, we demonstrate that the rs10993994 risk allele is associated with decreased expression of two MSMB isoforms in histologically normal and malignant prostate tissue. In addition, the risk allele is associated with increased expression of five NCOA4 isoforms in histologically normal prostate tissue only. No consistent association with either gene is observed in breast or colon tissue. In conjunction with these findings, suppression of MSMB expression or NCOA4 overexpression promotes anchorage-independent growth of prostate epithelial cells, but not growth of breast epithelial cells. These data suggest that germline variation at chromosome 10q11 contributes to prostate cancer risk by influencing expression of at least two genes. More broadly, the findings demonstrate that disease risk alleles may influence multiple genes, and associations between genotype and expression may only be observed in the context of specific tissue and disease states. C1 [Pomerantz, Mark M.; Shrestha, Yashaswi; Schafer, Eric J.; Loda, Massimo; Kantoff, Philip W.; Hahn, William C.; Freedman, Matthew L.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Pomerantz, Mark M.; Regan, Meredith M.; Mucci, Lorelei A.; Stampfer, Meir J.; Hunter, David J.; Richardson, Andrea L.; Loda, Massimo; Kantoff, Philip W.; Hahn, William C.] Harvard Univ, Sch Med, Boston, MA USA. [Shrestha, Yashaswi; Schafer, Eric J.; Loda, Massimo; Hahn, William C.; Freedman, Matthew L.] Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. [Shrestha, Yashaswi; Schafer, Eric J.; Loda, Massimo; Hahn, William C.; Freedman, Matthew L.] Harvard & Massachusetts Inst Technol, Broad Inst, Cambridge, MA USA. [Flavin, Richard J.; Loda, Massimo] Brigham & Womens Hosp, Dana Farber Canc Inst, Ctr Mol Oncol Pathol, Boston, MA 02115 USA. [Regan, Meredith M.] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Penney, Kathryn L.; Mucci, Lorelei A.; Stampfer, Meir J.; Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Mucci, Lorelei A.; Stampfer, Meir J.; Hunter, David J.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Stampfer, Meir J.; Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Chan, Jennifer A.] Univ Calgary, Dept Pathol & Lab Med, Calgary, AB, Canada. [Tabernero, Josep; Baselga, Jose] Vall dHebron Univ Hosp, Vall dHebron Inst Oncol, Barcelona, Spain. [Richardson, Andrea L.; Loda, Massimo] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Oh, William K.] Mt Sinai Sch Med, Tisch Canc Inst, New York, NY USA. RP Pomerantz, MM (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM freedman@broadinstitute.org RI Oh, William/B-9163-2012 OI Oh, William/0000-0001-5113-8147 FU Howard Hughes Medical Institute; Doris Duke Clinical Scientist Development Award; Claudia Adams Barr award; US National Institutes of Health [R01 CA129435]; Mayer Foundation; H.L. Snyder Medical Foundation; Dana-Farber/Harvard Cancer Center Prostate Cancer SPORE (National Cancer Institute) [5P50CA90381]; Emerald Foundation, Inc.; William L. Edwards-Prostate Cancer Foundation; Prostate Cancer Foundation; John Snyder Medical Foundation FX MLF is a Howard Hughes Medical Institute Physician-Scientist Early Career Awardee (www.hhmi.org), a recipient of a 2006 Doris Duke Clinical Scientist Development Award (www.ddcf.org), and a recipient of a 2009 Claudia Adams Barr award (www.dana-farber.org). This work was supported by grants from the US National Institutes of Health (R01 CA129435 to MLF), the Mayer Foundation (to MLF), the H.L. Snyder Medical Foundation (to MLF), the Dana-Farber/Harvard Cancer Center Prostate Cancer SPORE (National Cancer Institute Grant No. 5P50CA90381), and the Emerald Foundation, Inc. (to MLF). MMP is supported by the William L. Edwards-Prostate Cancer Foundation Young Investigator Award (www.prostatecancerfoundation.org). WCH receives support from the Prostate Cancer Foundation and the John Snyder Medical Foundation (snydermf.org). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 42 TC 39 Z9 40 U1 1 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7404 J9 PLOS GENET JI PLoS Genet. PD NOV PY 2010 VL 6 IS 11 AR e1001204 DI 10.1371/journal.pgen.1001204 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 684WX UT WOS:000284587100018 PM 21085629 ER PT J AU Chowdhury, F Khan, AI Faruque, ASG Ryan, ET AF Chowdhury, Fahima Khan, Ashraful Islam Faruque, Abu Syed Golam Ryan, Edward T. TI Severe, Acute Watery Diarrhea in an Adult SO PLOS NEGLECTED TROPICAL DISEASES LA English DT Editorial Material ID CHOLERA C1 [Chowdhury, Fahima; Khan, Ashraful Islam; Faruque, Abu Syed Golam] ICDDR B, Clinial Sci Div, Dhaka, Bangladesh. [Ryan, Edward T.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Ryan, Edward T.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Ryan, Edward T.] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Chowdhury, F (reprint author), ICDDR B, Clinial Sci Div, Dhaka, Bangladesh. EM etryan@partners.org FU FIC NIH HHS [R24 TW007988]; NIAID NIH HHS [U01 AI058935, U01 AI077883] NR 8 TC 4 Z9 4 U1 0 U2 0 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1935-2727 J9 PLOS NEGLECT TROP D JI Plos Neglect. Trop. Dis. PD NOV PY 2010 VL 4 IS 11 AR e898 DI 10.1371/journal.pntd.0000898 PG 4 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA 687GB UT WOS:000284765900039 PM 21152053 ER PT J AU Stineman, MG Streim, JE AF Stineman, Margaret Grace Streim, Joel E. TI The Biopsycho-ecological Paradigm: A Foundational Theory for Medicine SO PM&R LA English DT Review AB The current biomedical and psychosocial frameworks that form the conceptual basis of medicine today are insufficient to address the needs of the medically complex and environmentally challenged populations of patients often cared for by physical medicine and rehabilitation specialists. The expanded biopsycho-ecological model of health, illness, injury, and disability operating through mechanisms of Health Environmental Integration (HEI) encourages a more complete understanding of illness, injury, activity limitation, and participation restriction as arising at the interface between the person and the environment. HEI recognizes complex interacting multilevel functional hierarchies beginning at the cellular level and ending at the individual's experience of the environment. Although the foci of illness and injury are within the body and mind, the physical and social environments contain elements that can cause or exacerbate disease and barriers that interact in ways that lead to injuries and disabilities. Furthermore, these environments hold the elements from which treating agents, facilitators, and social supports must be fashioned. The highly integrative biopsycho-ecological framework provides an expanded basis for understanding the objective causes and subjective meanings of disabilities. Disabilities are reduced through HEI by seeking to maximally integrate the body and mind (the self) with both the surrounding physical environment and other people in society. HEI offers mechanisms for interdisciplinary research, an expanded framework for education and empowerment, and a blueprint for optimizing day-to-day clinical care at both the individual patient and treatment population levels in the ever-changing scientific, political, and policy environments. PM R 2010;2:1035-1045 C1 [Stineman, Margaret Grace] Ctr Clin Epidemiol & Biostat, Dept Phys Med & Rehabil, Philadelphia, PA 19104 USA. [Streim, Joel E.] Univ Penn, Geriatr Psychiat Sect, Philadelphia, PA 19104 USA. [Streim, Joel E.] Philadelphia Vet Affairs Med Ctr, VISN Mental Illness Res Clin & Educ Ctr 4, Philadelphia, PA USA. RP Stineman, MG (reprint author), Ctr Clin Epidemiol & Biostat, Dept Phys Med & Rehabil, 904 Blockley Hall,423 Guardian Dr, Philadelphia, PA 19104 USA. EM mstinema@mail.med.upenn.edu FU NIH [R01-AG032420] FX This work was supported in part by grant R01-AG032420 from the NIH. NR 93 TC 19 Z9 20 U1 2 U2 15 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1934-1482 J9 PM&R JI PM&R PD NOV PY 2010 VL 2 IS 11 BP 1035 EP 1045 DI 10.1016/j.pmrj.2010.06.013 PG 11 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA V24LS UT WOS:000208412500008 PM 21093839 ER PT J AU Pitman, RK Kaelin, D Zafonte, R Pitman, RK Kaelin, D Zafonte, R AF Pitman, Roger K. Kaelin, Darryl Zafonte, Ross Pitman, Roger K. Kaelin, Darryl Zafonte, Ross TI Posttraumatic Stress Disorder Versus Traumatic Brain Injury SO PM&R LA English DT Editorial Material C1 [Zafonte, Ross] Spaulding Rehab Hosp, Boston, MA 02114 USA. [Pitman, Roger K.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Kaelin, Darryl] Shepherd Ctr, Acquired Brain Injury Program, Atlanta, GA USA. RP Zafonte, R (reprint author), Spaulding Rehab Hosp, 125 Nashua St, Boston, MA 02114 USA. EM rzafonte@partners.org; rzafonte@partners.org NR 27 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1934-1482 J9 PM&R JI PM&R PD NOV PY 2010 VL 2 IS 11 BP 1051 EP 1054 DI 10.1016/j.pmrj.2010.10.008 PG 4 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA V24LS UT WOS:000208412500010 PM 21093841 ER PT J AU Forman, DE Myers, J Lavie, CJ Guazzi, M Celli, B Arena, R AF Forman, Daniel E. Myers, Jonathan Lavie, Carl J. Guazzi, Marco Celli, Bartolome Arena, Ross TI Cardiopulmonary Exercise Testing: Relevant But Underused SO POSTGRADUATE MEDICINE LA English DT Article DE cardiopulmonary exercise testing; functional capacity; diagnosis; prognosis ID CHRONIC HEART-FAILURE; PRIMARY PULMONARY-HYPERTENSION; TIDAL CARBON-DIOXIDE; CORONARY-ARTERY-DISEASE; PEAK OXYGEN-CONSUMPTION; CARDIAC-OUTPUT; RATE RECOVERY; CHRONOTROPIC INCOMPETENCE; SCIENTIFIC STATEMENT; PROGNOSTIC VALUE AB Cardiopulmonary exercise testing (CPX) is a relatively old technology, but has sustained relevance for many primary care clinical scenarios in which it is, ironically, rarely considered. Advancing computer technology has made CPX easier to administer and interpret at a time when our aging population is more prone to comorbidities and higher prevalence of nonspecific symptoms of exercise intolerance and dyspnea, for which CPX is particularly useful diagnostically and prognostically. These discrepancies in application are compounded by patterns in which CPX is often administered and interpreted by cardiology, pulmonary, or exercise specialists who limit their assessments to the priorities of their own discipline, thereby missing opportunities to distinguish symptom origins. When used properly, CPX enables the physician to assess fitness and uncover cardiopulmonary issues at earlier phases of work-up, which would therefore be especially useful for primary care physicians. In this article, we provide an overview of CPX principles and testing logistics, as well as some of the clinical contexts in which it can enhance patient care. C1 [Forman, Daniel E.] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA. [Forman, Daniel E.] VA Boston Healthcare Syst, Div Cardiol, Boston, MA USA. [Myers, Jonathan] VA Palo Alto Hlth Care Syst, Div Cardiol, Palo Alto, CA USA. [Lavie, Carl J.] Univ Queensland, Sch Med, John Ochsner Heart & Vasc Inst, Ochsner Clin Sch, New Orleans, LA USA. [Guazzi, Marco] Univ Milan, San Paolo Hosp, Div Cardiol, Cardiopulm Lab, Milan, Italy. [Celli, Bartolome] Brigham & Womens Hosp, Div Pulm Med, Boston, MA 02115 USA. [Arena, Ross] Virginia Commonwealth Univ, Dept Internal Med, Richmond, VA USA. [Arena, Ross] Virginia Commonwealth Univ, Dept Physiol, Richmond, VA USA. [Arena, Ross] Virginia Commonwealth Univ, Dept Phys Therapy, Richmond, VA USA. RP Forman, DE (reprint author), Brigham & Womens Hosp, Div Cardiovasc Med, 75 Francis St, Boston, MA 02115 USA. EM deforman@partners.org RI Lavie, Carl/A-6014-2011; Arena, Ross/A-3141-2008; Guazzi, Marco/J-3165-2016 OI Arena, Ross/0000-0002-6675-1996; Guazzi, Marco/0000-0002-8456-609X NR 97 TC 22 Z9 25 U1 0 U2 10 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0032-5481 EI 1941-9260 J9 POSTGRAD MED JI Postgrad. Med. PD NOV PY 2010 VL 122 IS 6 BP 68 EP 86 DI 10.3810/pgm.2010.11.2225 PG 19 WC Medicine, General & Internal SC General & Internal Medicine GA 711VB UT WOS:000286618400009 PM 21084784 ER PT J AU Rotondi, AJ Anderson, CM Haas, GL Eack, SM Spring, MB Ganguli, R Newhill, C Rosenstock, J AF Rotondi, Armando J. Anderson, Carol M. Haas, Gretchen L. Eack, Shaun M. Spring, Michael B. Ganguli, Rohan Newhill, Christina Rosenstock, Jason TI Web-Based Psychoeducational Intervention for Persons With Schizophrenia and Their Supporters: One-Year Outcomes SO PSYCHIATRIC SERVICES LA English DT Article ID PSYCHIATRIC-INPATIENTS; FAMILY MANAGEMENT; FEASIBILITY; RELAPSE; METAANALYSIS; PREVENTION; ILLNESS; CARE AB Objective: This study examined the use of a uniquely designed Web site and home computers to deliver online multifamily psychoeducational therapy to persons with schizophrenia and their informal supports (family and friends). Web site usage and outcome benefits are reported. Methods: Thirty-one persons with schizophrenia or schizoaffective disorder and 24 support persons were randomly assigned to the online intervention (telehealth) or treatment as usual (usual care) condition. At three, six, and 12 months, interviewer-administered assessments were conducted with participants. Intention-to-treat analyses compared persons with schizophrenia in the two study conditions on severity of positive symptoms and knowledge of schizophrenia. Support persons in the two study conditions were compared on knowledge of schizophrenia. Each participant's usage of the Web site was logged. Results: Persons with schizophrenia in the telehealth condition had a large and significant reduction in positive symptoms (p=.042, d=-.88) and a large and significant increase in knowledge of schizophrenia compared with their counterparts in the usual care condition. Support persons in the telehealth condition showed a large and significant increase in knowledge about prognosis compared with those in the usual care condition (p=.036, d=1.94). Persons with schizophrenia used the Web site to a much greater extent (pages viewed and time spent) than support persons. Conclusions: These findings suggest that online delivery of psychotherapeutic treatment and educational resources to consumers' homes has considerable potential to improve consumer well-being and offers several advantages over standard clinic-based delivery models. (Psychiatric Services 61: 1099-1105, 2010) C1 [Rotondi, Armando J.] Univ Pittsburgh, Dept Crit Care Med, Pittsburgh, PA 15260 USA. [Eack, Shaun M.; Newhill, Christina] Univ Pittsburgh, Dept Social Work, Pittsburgh, PA 15260 USA. [Spring, Michael B.] Univ Pittsburgh, Dept Informat Sci, Pittsburgh, PA 15260 USA. [Anderson, Carol M.; Haas, Gretchen L.; Ganguli, Rohan; Rosenstock, Jason] Univ Pittsburgh, Med Ctr, Dept Psychiat, Pittsburgh, PA 15260 USA. [Rotondi, Armando J.; Haas, Gretchen L.] Vet Affairs Pittsburgh Healthcare Syst, Vet Integrated Serv Network 4, Mental Illness Res Educ & Clin Ctr, Pittsburgh, PA USA. RP Rotondi, AJ (reprint author), Univ Pittsburgh, Dept Crit Care Med, 644 Scaife Hall,3550 Terrace St, Pittsburgh, PA 15260 USA. EM rotondi@pitt.edu RI lyp, maggie/G-1471-2011 FU National Institute of Mental Health [R01 MH63484]; Abbott Laboratories; Bristol Myers-Squibb FX This project was supported by grant R01 MH63484 from the National Institute of Mental Health.; Dr. Eack receives consulting fees from Abbott Laboratories. Dr. Ganguli is a consultant for Janssen Pharmaceuticals, Johnson & Johnson, and Eli Lilly and Company, and he works under a research grant funded by Bristol MyersSquibb. The other authors report no competing interests. NR 38 TC 55 Z9 55 U1 6 U2 25 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 2010 VL 61 IS 11 BP 1099 EP 1105 PG 7 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 673IA UT WOS:000283651500010 PM 21041348 ER PT J AU Recklitis, CJ Varela, VS Ng, A Mauch, P Bober, S AF Recklitis, Christopher J. Varela, Veronica Sanchez Ng, Andrea Mauch, Peter Bober, Sharon TI Sexual functioning in long-term survivors of Hodgkin's lymphoma SO PSYCHO-ONCOLOGY LA English DT Article DE Hodgkin's lymphoma; long-term survivors; sexual dysfunctions; survey; cancer; oncology ID QUALITY-OF-LIFE; PSYCHOSOCIAL ADAPTATION; UNITED-STATES; DISEASE; PREVALENCE; OUTCOMES; CANCER AB Objective: Studies of Hodgkin's lymphoma (HL) survivors have reported long-term adjustment problems including sexual dysfunction, but the prevalence and persistence of sexual problems in HL survivors have not been well characterized. This study aimed to address these questions by comparing sexual health in a large cohort of long-term HL survivors with a noncancer control group. Methods: A mailed survey including questions about current sexual problems and sexual satisfaction was completed by 465 HL survivors and 205 sibling controls. Survivors ranged from 20 to 82 years (median = 44) and were treated >= 7 years prior (median = 18). Results: Sexual problems were commonly reported by HL survivors, with 54.2% reporting decreased sexual activity and 41.4% reporting decreased interest. When survivors' current sexual functioning was compared with the control group, however, no differences were found, and overall sexual satisfaction was positive in both groups. Among survivors, age was not associated with sexual problems but had a small significant negative association with satisfaction (rho = -0.12; p<0.05). No associations between time since diagnosis, disease stage, and chemotherapy treatment and sexual functioning were found. Conclusions: Consistent with previous studies, HL survivors reported high rates of current sexual problems. However, no differences in sexual problems or sexual satisfaction were found between survivors and controls. Results indicate that over the long term, survivors' sexual functioning does not differ from noncancer controls. Findings underscore the importance of including healthy control groups to determine whether difficulties reported by cancer survivors can be attributed to cancer treatment. Copyright (C) 2009 John Wiley & Sons, Ltd. C1 [Recklitis, Christopher J.; Varela, Veronica Sanchez; Bober, Sharon] Dana Farber Canc Inst, Perini Family Survivors Ctr, Boston, MA 02115 USA. [Recklitis, Christopher J.; Varela, Veronica Sanchez; Ng, Andrea; Mauch, Peter; Bober, Sharon] Harvard Univ, Sch Med, Boston, MA USA. [Ng, Andrea; Mauch, Peter] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Recklitis, CJ (reprint author), Dana Farber Canc Inst, Perini Family Survivors Ctr, 44 Binney St, Boston, MA 02115 USA. EM Christopher_Recklitis@dfci.harvard.edu NR 19 TC 12 Z9 12 U1 1 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1057-9249 J9 PSYCHO-ONCOLOGY JI Psycho-Oncol. PD NOV PY 2010 VL 19 IS 11 BP 1229 EP 1233 DI 10.1002/pon.1679 PG 5 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 678AY UT WOS:000284041000013 PM 20035526 ER PT J AU Antshel, KM Faraone, SV Maglione, K Doyle, AE Fried, R Seidman, LJ Biederman, J AF Antshel, K. M. Faraone, S. V. Maglione, K. Doyle, A. E. Fried, R. Seidman, L. J. Biederman, J. TI Executive functioning in high-IQ adults with ADHD SO PSYCHOLOGICAL MEDICINE LA English DT Article DE Adult ADHD; executive functioning; IQ ID DEFICIT-HYPERACTIVITY DISORDER; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; MGH LONGITUDINAL FAMILY; SUBTHRESHOLD DIAGNOSES; LATE-ONSET; VALID DIAGNOSIS; CHILDREN; STABILITY; NEUROPSYCHOLOGY; INTELLIGENCE AB Background. To examine the association between psychological tests of executive functioning and functional outcomes among high-IQ adults with attention deficit hyperactivity disorder (ADHD). Method. Subjects were high-IQ adults with (n=64) and without ADHD (n=53). Subjects were administered a battery of neuropsychological tests assessing executive functioning. Results. High-IQ adults with ADHD performed less well than those without ADHD on several psychological tests of executive functioning, including the Wisconsin Card Sorting Test (WCST), Stroop Color and Word Test, Rey-Osterrieth Complex Figure Test (ROCF), California Verbal Learning Test (CVLT) and an auditory continuous performance test (CPT). Test performance in the high-IQ adult ADHD group, however, was average. In the entire sample, performance on several tests of executive functioning including the ROCF and the CVLT were significant predictors of real-world functioning. Conclusions. High-IQ adults with ADHD perform less well on tests of executive functioning relative to high-IQ control participants. Performance on several tests of executive functioning was a significant predictor of functioning. C1 [Antshel, K. M.; Faraone, S. V.; Maglione, K.] SUNY Upstate Med Univ, Dept Psychiat & Behav Sci, Syracuse, NY USA. [Doyle, A. E.; Fried, R.; Seidman, L. J.; Biederman, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Doyle, A. E.; Fried, R.; Seidman, L. J.; Biederman, J.] Harvard Univ, Sch Med, Boston, MA USA. RP Faraone, SV (reprint author), SUNY Upstate Med Univ, Dept Psychiat & Behav Sci, Syracuse, NY USA. EM faraones@upstate.edu OI Faraone, Stephen/0000-0002-9217-3982 NR 50 TC 26 Z9 29 U1 3 U2 27 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0033-2917 J9 PSYCHOL MED JI Psychol. Med. PD NOV PY 2010 VL 40 IS 11 BP 1909 EP 1918 DI 10.1017/S0033291709992273 PG 10 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 675BR UT WOS:000283799300019 PM 20085666 ER PT J AU Herbst, E Metzler, TJ Lenoci, M McCaslin, SE Inslicht, S Marmar, CR Neylan, TC AF Herbst, Ellen Metzler, Thomas J. Lenoci, Maryann McCaslin, Shannon E. Inslicht, Sabra Marmar, Charles R. Neylan, Thomas C. TI Adaptation effects to sleep studies in participants with and without chronic posttraumatic stress disorder SO PSYCHOPHYSIOLOGY LA English DT Article DE Posttraumatic stress disorder; Adaptation effects; First night effect; Ambulatory polysomnography ID ADMINISTERED PTSD SCALE; PITUITARY-ADRENAL AXIS; LABORATORY ADAPTATION; VIETNAM VETERANS; NIGHT; HOME; DISTURBANCES; VARIABILITY; PARAMETERS; INSOMNIACS AB The "first night effect" (FNE) is the alteration of sleep architecture observed on the first night of polysomnographic (PSG) studies. It is unclear whether the FNE reflects adaptation to the equipment, sleeping environment, or both. Moreover, it is possible that certain patient populations, such as those with posttraumatic stress disorder (PTSD), demonstrate greater adaptation effects that are highly context dependent. We assessed FNE in participants with PTSD and healthy controls in a cross-sectional study consisting of PSG testing at home and in the hospital. Contrary to our expectations, the PTSD group showed no adaptation effects in either setting. Only the control group assigned to the "hospital first" condition showed significant decreases in total sleep time on night 1 versus night 2 of the study. The results suggest that the FNE is related to adaptation to the combination of the hospital environment and the recording equipment. C1 [Herbst, Ellen; Metzler, Thomas J.; McCaslin, Shannon E.; Inslicht, Sabra; Marmar, Charles R.; Neylan, Thomas C.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Herbst, Ellen; Metzler, Thomas J.; Lenoci, Maryann; McCaslin, Shannon E.; Inslicht, Sabra; Marmar, Charles R.; Neylan, Thomas C.] San Francisco VA Med Ctr, Psychiat Serv, San Francisco, CA USA. RP Neylan, TC (reprint author), VA Med Ctr, Psychiat Serv 116P, PTSD Program, 4150 Clement St, San Francisco, CA 94121 USA. EM Thomas.Neylan@ucsf.edu FU National Institutes of Health [MH057157, MH73978]; Sierra Pacific Mental Illness and Education Clinical Center (MIRECC); NIH/NCRRUCSF-CTSI [UL1 RR024131] FX This work was supported by the National Institutes of Health (TCN: MH057157 & MH73978), the Sierra Pacific Mental Illness and Education Clinical Center (MIRECC), and from the NIH/NCRRUCSF-CTSI Grant Number UL1 RR024131. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. NR 36 TC 11 Z9 12 U1 1 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0048-5772 J9 PSYCHOPHYSIOLOGY JI Psychophysiology PD NOV PY 2010 VL 47 IS 6 BP 1127 EP 1133 DI 10.1111/j.1469-8986.2010.01030.x PG 7 WC Psychology, Biological; Neurosciences; Physiology; Psychology; Psychology, Experimental SC Psychology; Neurosciences & Neurology; Physiology GA 663HU UT WOS:000282874800016 PM 20456661 ER PT J AU Freudenreich, O Kontos, N Tranulis, C Cather, C AF Freudenreich, Oliver Kontos, Nicholas Tranulis, Constantin Cather, Corinne TI Morgellons Disease, or Antipsychotic-Responsive Delusional Parasitosis, in an HIV Patient: Beliefs in The Age of the Internet SO PSYCHOSOMATICS LA English DT Article ID SOMATIC SYNDROMES; THERAPY; MODEL C1 [Freudenreich, Oliver; Cather, Corinne] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kontos, Nicholas] Cambridge Hlth Alliance, Cambridge, MA USA. [Tranulis, Constantin] Louis H Lafontaine Hosp, Montreal, PQ, Canada. [Freudenreich, Oliver; Kontos, Nicholas; Cather, Corinne] Harvard Univ, Sch Med, Boston, MA USA. [Tranulis, Constantin] Univ Montreal, Montreal, PQ, Canada. RP Freudenreich, O (reprint author), Freedom Trail Clin, MGH Schizophrenia Program, 25 Staniford St,2nd Floor, Boston, MA 02114 USA. EM ofreudenreich@partners.org NR 21 TC 7 Z9 8 U1 0 U2 1 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 2010 VL 51 IS 6 BP 453 EP 457 PG 5 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 675SG UT WOS:000283851800001 PM 21051675 ER PT J AU Viron, MJ Stern, TA AF Viron, Mark J. Stern, Theodore A. TI The Impact of Serious Mental Illness on Health and Healthcare SO PSYCHOSOMATICS LA English DT Review ID CHRONIC MEDICAL ILLNESSES; ANTIPSYCHOTIC-DRUGS; CARDIOVASCULAR PROCEDURES; MYOCARDIAL-INFARCTION; PSYCHIATRIC-DISORDERS; BIPOLAR DISORDER; EXCESS MORTALITY; VA PATIENTS; BASE-LINE; SCHIZOPHRENIA AB Background: Patients with serious mental illness (SMI; e.g., psychotic disorders and major mood disorders) die earlier, have more medical illnesses, and receive worse medical care than those in the general population. Objective: The aims of this article are to review the data on medical morbidity and mortality in those with SMI, to highlight the factors that lead to such disparities, and to discuss potential solutions to the problem. Method: The authors reviewed the literature on medical morbidity and mortality in those with SMI. Results: Adults with SMI in the United States die 25 years earlier than those in the general population; cardiovascular disease is responsible for the majority of this excess mortality, accounting for roughly 50%-60% of the deaths due to medical illness. Patient, provider, and system-level factors interact to contribute to poor health outcomes in people with SMI. Conclusion: Patients with SMI are losing many years of life to preventable and treatable medical illnesses. Solutions to the problem will require attention to patient, provider, and system-level factors. (Psychosomatics 2010; 51: 458-465) C1 [Viron, Mark J.; Stern, Theodore A.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Viron, MJ (reprint author), Massachusetts Gen Hosp, Dept Psychiat, 15 Parkman St,WACC 812, Boston, MA 02114 USA. EM mviron@partners.org NR 75 TC 49 Z9 49 U1 4 U2 16 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD NOV-DEC PY 2010 VL 51 IS 6 BP 458 EP 465 PG 8 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 675SG UT WOS:000283851800002 PM 21051676 ER PT J AU Freudenreich, O Goforth, HW Cozza, KL Mimiaga, MJ Safren, SA Bachmann, G Cohen, MA AF Freudenreich, Oliver Goforth, Harold W. Cozza, Kelly L. Mimiaga, Matthew J. Safren, Steven A. Bachmann, Grace Cohen, Mary Ann TI Psychiatric Treatment of Persons With HIV/AIDS: An HIV-Psychiatry Consensus Survey of Current Practices SO PSYCHOSOMATICS LA English DT Article ID PLACEBO-CONTROLLED TRIAL; DOUBLE-BLIND; PART 1; DEPRESSION; DISEASE; DISORDERS; FATIGUE; AIDS; ANTIRETROVIRALS; INDIVIDUALS AB Background: Only sparse evidence from controlled clinical trials is available to guide the psychiatric treatment of persons with HIV/AIDS. Objective: The authors assessed and determined current treatment trends in AIDS psychiatry. Method: Members of the Organization of AIDS Psychiatry (OAP) participated in a web-based survey. Results: Of 159 members, 62 (39%) responded to the survey. Consensus emerged regarding first-line treatment for depression (escitalopram/citalopram), for psychosis and secondary mania (quetiapine), and for anxiety (clonazepam). Conclusion: Consensus statements can serve as a preliminary step toward providing some standardization of care for persons with HIV/AIDS. (Psychosomatics 2010; 51:480-488) C1 [Freudenreich, Oliver; Mimiaga, Matthew J.; Safren, Steven A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat, Boston, MA USA. [Goforth, Harold W.] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC USA. [Cozza, Kelly L.] Durham Vet Affairs Med Ctr, Dept Psychiat, Durham, NC USA. [Cozza, Kelly L.] GRECC, Div Palliat Med, Dept Psychiat, Durham, NC USA. [Cozza, Kelly L.] Uniformed Serv Univ Hlth Sci, Dept Psychiat, Bethesda, MD 20814 USA. [Cohen, Mary Ann] Mt Sinai Sch Med, New York, NY USA. RP Freudenreich, O (reprint author), Freedom Trail Clin, 25 Staniford St, Boston, MA 02114 USA. EM ofreudenreich@partners.org FU AstraZeneca; BMS; Janssen Pharmaceutica; Eli Lilly and Company; Pfizer Inc.; U.S. Pharmaceuticals Group FX Dr. Freudenreich has received support from AstraZeneca, BMS, Janssen Pharmaceutica, Eli Lilly and Company, Pfizer Inc., U.S. Pharmaceuticals Group, and Reed Medical Education (all for CME activities); and Beacon Health Strategies (as a consultant). Dr. Goforth has received support from BMS (consultant and speaker). Drs. Cozza, Mimiaga, Safren, and Cohen, as well as Mrs. Bachman report no conflict of interest related to this study. NR 39 TC 9 Z9 9 U1 2 U2 5 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0033-3182 J9 PSYCHOSOMATICS JI Psychosomatics PD NOV-DEC PY 2010 VL 51 IS 6 BP 480 EP 488 PG 9 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 675SG UT WOS:000283851800005 PM 21051679 ER PT J AU Kunkel, EJS del Busto, E Kathol, R Stern, TA Wise, TN Stoddard, FR Straus, J Saravay, SM Muskin, PR Dresner, N Harrington, CJ Weiner, J Barnhill, J Becker, M Joseph, RC Oyesanmi, O Fann, JR Colon, E Epstein, S Weinrieb, R AF Kunkel, Elisabeth J. S. del Busto, Elena Kathol, Roger Stern, Theodore A. Wise, Thomas N. Stoddard, Frederick R., II Straus, Joshua Saravay, Stephen M. Muskin, Philip R. Dresner, Nehama Harrington, Colin J. Weiner, Joseph Barnhill, John Becker, Madeleine Joseph, Robert C. Oyesanmi, Olugbenga Fann, Jesse R. Colon, Eduardo Epstein, Steven Weinrieb, Robert TI Physician Staffing for the Practice of Psychosomatic Medicine in General Hospitals: A Pilot Study SO PSYCHOSOMATICS LA English DT Article ID CONSULTATION-LIAISON; PSYCHIATRIC-CONSULTATION; CONSTANT OBSERVATION; HEALTH-SERVICES; INPATIENTS; LENGTH; STAY; CHALLENGES; DISORDERS; IMPACT AB Background: The treatment of psychiatric illnesses, prevalent in the general hospital, requires broadly trained providers with expertise at the interface of psychiatry and medicine. Since each hospital operates under different economic constraints, it is difficult to establish an appropriate ratio of such providers to patients. Objective: The authors sought to determine the current staffing patterns and ratios of Psychosomatic Medicine practitioners in general hospitals, to better align manpower with clinical service and educational requirements on consultation-liaison psychiatry services. Method: Program directors of seven academic Psychosomatic Medicine ( PM) programs in the Northeast were surveyed to establish current staffing patterns and patient volumes. Survey data were reviewed and analyzed along with data from the literature and The Academy of Psychosomatic Medicine (APM) fellowship directory. Results: Staffing patterns varied widely, both in terms of the number and disciplines of staff providing care for medical and surgical inpatients. The ratio of initial consultations performed per hospital bed varied from 1.6 to 4.6. Conclusion: Although staffing patterns vary, below a minimum staffing level, there is likely to be significant human and financial cost. Efficient sizing of a PM staff must be accomplished in the context of a given institution's patient population, the experience of providers, the presence/absence and needs of trainees, and the financial constraints of the department and institution. National survey data are needed to provide benchmarks for both academic and non-academic PM services. (Psychosomatics 2010; 51:520-527) C1 [Kunkel, Elisabeth J. S.] Thomas Jefferson Univ, Dept Psychiat & Human Behav, Philadelphia, PA 19107 USA. Univ Minnesota, Dept Internal Med & Psychiat, Minneapolis, MN 55455 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cambridge, MA 02138 USA. Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21205 USA. Drexel Univ, Coll Med, Dept Pathol, Philadelphia, PA 19104 USA. Drexel Univ, Coll Med, Dept Surg, Philadelphia, PA 19104 USA. Northwestern Univ, Evanston Hosp, Dept Outpatient Psychosomat Med, Evanston, IL 60201 USA. Albert Einstein Coll Med, Dept Psychiat, Bronx, NY 10467 USA. Long Isl Jewish Med Ctr, Psychiat Consultation Liaison Serv, Long Isl City, NY USA. Columbia Univ, Coll Phys & Surg, New York, NY USA. Northwestern Univ, Wellsprings Hlth Associates, Chicago, IL 60611 USA. Northwestern Univ, Dept Psychiat & Behav Sci, Chicago, IL 60611 USA. Northwestern Univ, Dept Obstet & Gynecol, Feinberg Sch Med, Chicago, IL 60611 USA. Brown Med Sch, Dept Psychiat & Med, Providence, RI USA. New York Presbyterian Hosp, Weill Cornell Med Ctr, Dept Clin Psychiat, New York, NY USA. Cambridge Hlth Alliance, Cambridge, MA USA. ECRI Inst, Plymouth Meeting, PA USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98195 USA. Univ Minnesota, Hennepin Cty Med Ctr, Dept Psychiat, Minneapolis, MN 55415 USA. Georgetown Univ Hosp, Dept Psychiat, Washington, DC 20007 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Sch Med, Washington, DC USA. RP Kunkel, EJS (reprint author), Thomas Jefferson Univ, Dept Psychiat & Human Behav, 1020 Sansom St,Suite 1652, Philadelphia, PA 19107 USA. EM elisabeth.kunkel@jefferson.edu NR 30 TC 2 Z9 2 U1 0 U2 4 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 2010 VL 51 IS 6 BP 520 EP 527 PG 8 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 675SG UT WOS:000283851800011 PM 21051685 ER PT J AU Soskin, DP Kane, AJ Stern, TA AF Soskin, David P. Kane, Ari J. Stern, Theodore A. TI Phenytoin Toxicity Secondary to an Oxcarbazepine-Phenytoin 2C19 Interaction SO PSYCHOSOMATICS LA English DT Article ID BIPOLAR DISORDER; EPILEPTIC PATIENTS; PHARMACOKINETICS; CARBAMAZEPINE; SOFTWARE AB Background: Polytherapy is common in the management of bipolar disorder, as are the side effects associated with this treatment strategy. Objective: The authors review the literature on drug-drug interactions involving oxcarbazepine and identify specific mechanisms that may have clinical importance. Method: The authors provide a case report of a patient who developed phenytoin toxicity associated with an oxcarbazepine-phenytoin interaction. Results: Co-administration of phenytoin and oxcarbazepine resulted in toxic levels of phenytoin. Therefore, the patient's daily dosage of oxcarbazepine and phenytoin were reduced. Discussion: Although oxcarbazepine is an inducer of the 3A4 isoenzyme, it acts as an inhibitor of the 2C19 isoenzyme, and it can raise levels of other agents, for example, phenytoin, that are also metabolized by this isoenzyme. (Psychosomatics 2010; 51:532-535) C1 [Soskin, David P.] Massachusetts Gen Hosp, McLean Dept Psychiat, Boston, MA 02114 USA. Univ Calif San Francisco, Sch Med, San Francisco, CA USA. RP Soskin, DP (reprint author), Massachusetts Gen Hosp, McLean Dept Psychiat, Boston, MA 02114 USA. EM dsoskin@partners.org NR 17 TC 5 Z9 5 U1 0 U2 0 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 2010 VL 51 IS 6 BP 532 EP 535 PG 4 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 675SG UT WOS:000283851800014 PM 21051688 ER PT J AU Querques, J AF Querques, John TI Handbook of AIDS Psychiatry SO PSYCHOSOMATICS LA English DT Book Review C1 [Querques, John] Massachusetts Gen Hosp, Psychosomat Med Consultat Psychiat Fellowship Pro, Boston, MA 02114 USA. RP Querques, J (reprint author), Massachusetts Gen Hosp, Psychosomat Med Consultat Psychiat Fellowship Pro, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 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 2010 VL 51 IS 6 BP 540 EP 540 PG 1 WC Psychiatry; Psychology SC Psychiatry; Psychology GA 675SG UT WOS:000283851800018 ER PT J AU Biddinger, PD Savoia, E Massin-Short, SB Preston, J Stoto, MA AF Biddinger, Paul D. Savoia, Elena Massin-Short, Sarah B. Preston, Jessica Stoto, Michael A. TI Public Health Emergency Preparedness Exercises: Lessons Learned SO PUBLIC HEALTH REPORTS LA English DT Article ID TABLETOP EXERCISES AB The Harvard School of Public Health Center for Public Health Preparedness exercise program has two aims: (1) educating the public health workforce on key public health system emergency preparedness issues, and (2) identifying specific systems-level challenges in the public health response to large-scale events. Rigorous evaluation of 38 public health emergency preparedness (PHEP) exercises employing realistic scenarios and reliable and accurate outcome measures has demonstrated the usefulness of PHEP exercises in clarifying public health workers' roles and responsibilities, facilitating knowledge transfer among these individuals and organizations, and identifying specific public health systems-level challenges. C1 [Savoia, Elena] Harvard Univ, Sch Publ Hlth, Ctr Publ Hlth Preparedness, Landmark Ctr, Boston, MA 02115 USA. [Biddinger, Paul D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Savoia, Elena; Massin-Short, Sarah B.] Harvard Univ, Sch Publ Hlth, Div Publ Hlth Practice, Boston, MA 02115 USA. [Stoto, Michael A.] Georgetown Univ, Sch Nursing & Hlth Studies, Washington, DC USA. RP Savoia, E (reprint author), Harvard Univ, Sch Publ Hlth, Ctr Publ Hlth Preparedness, Landmark Ctr, 677 Huntington Ave,3rd Floor E, Boston, MA 02115 USA. EM esavoia@hsph.harvard.edu FU Centers for Disease Control and Prevention (CDC) [3U90TP124242-05SI, 5P0ITP000307-01] FX This article was developed in collaboration with a number of partnering organizations, and with funding support awarded to the HSPH-CPHP under Centers for Disease Control and Prevention (CDC) Grant/Cooperative Agreement #3U90TP124242-05SI and #5P0ITP000307-01 (Preparedness and Emergency Response Research Center). The content of this article and the views and discussions expressed in this article are solely those of the authors and do not necessarily represent the views of any partner organizations, CDC, or HHS, nor does the mention of trade names, commercial practices, or organizations imply endorsement by the U.S. government. NR 20 TC 17 Z9 17 U1 0 U2 4 PU ASSOC SCHOOLS PUBLIC HEALTH PI WASHINGTON PA 1101 15TH ST NW, STE 910, WASHINGTON, DC 20005 USA SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PD NOV-DEC PY 2010 VL 125 SU 5 BP 100 EP 106 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 667RK UT WOS:000283211200014 PM 21133066 ER PT J AU Kalli, S Freer, PE Rafferty, EA AF Kalli, Sirishma Freer, Phoebe E. Rafferty, Elizabeth A. TI Lesions of the Skin and Superficial Tissue at Breast MR Imaging SO RADIOGRAPHICS LA English DT Article ID RADIOLOGIC-PATHOLOGICAL CORRELATION; NIPPLE-AREOLAR COMPLEX; OF-THE-LITERATURE; VASCULAR TUMORS; DERMATOFIBROSARCOMA PROTUBERANS; CONSERVING SURGERY; RADIATION-THERAPY; CANCER; CARCINOMA; FEATURES AB Although numerous studies have outlined the benefits of contrast material-enhanced magnetic resonance (MR) imaging for the detection of breast parenchymal findings, the assessment of lesions of the skin and superficial tissue at breast MR imaging has largely been overlooked. Such lesions, both benign and malignant, are commonly encountered at breast MR imaging, and their detection and diagnosis are often imperative. These lesions include superficial, locally extensive, inflammatory, and recurrent breast cancers; iatrogenic changes; sebaceous cysts; and less prevalent diseases such as granulomatous mastitis and angiosarcomas, among others. As MR imaging continues to be used with increasing frequency in both the screening and diagnostic settings, these lesions will be encountered more often; consequently, a better understanding of which lesions may be ignored and which require further evaluation will become increasingly important. Frequently, MR imaging alone may not clearly indicate the cause of lesions of the breast skin and superficial tissue. However, radiologists should thoroughly assess such lesions, taking into consideration the spectrum of possible causes. Mammography, ultrasonography, consultation with clinicians or dermatologists regarding physical examination findings, and, when necessary, correlation with pathologic findings in biopsy specimens may be used in conjunction with MR imaging to establish both the importance of these lesions and their definitive diagnoses. (C) RSNA, 2010. radiographics.rsna.org C1 [Kalli, Sirishma; Freer, Phoebe E.; Rafferty, Elizabeth A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Freer, PE (reprint author), Massachusetts Gen Hosp, Dept Radiol, 15 Parkman St,Wang ACC 240, Boston, MA 02114 USA. EM pfreer@partners.org OI Freer, Phoebe/0000-0001-6886-7100 NR 64 TC 11 Z9 12 U1 0 U2 4 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0271-5333 J9 RADIOGRAPHICS JI Radiographics PD NOV PY 2010 VL 30 IS 7 BP 1891 EP 1913 DI 10.1148/rg.307105064 PG 23 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 678QF UT WOS:000284094200010 PM 21057126 ER PT J AU Sorensen, AG AF Sorensen, A. Gregory TI Science to Practice: Blood-Brain Barrier Leakage-One Size Does Not Fit All SO RADIOLOGY LA English DT Editorial Material AB While radiologists often think of brain lesions as either enhancing or nonenhancing, the permeability of the blood-brain barrier in fact depends on the size, charge, and composition of whatever is used to measure permeability, and disease can alter this permeability in a variety of ways. Lemasson et al (1) use gadolinium chelates of two different sizes in a rat model of glioma and show that lesions can show differential enhancement after radiation therapy and antiangiogenic therapies. This is presumably because of different sized microfenestrations. We as radiologists need to increase the sophistication of our thinking about how we assess abnormalities of the blood-brain barrier. C1 Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Boston, MA 02129 USA. RP Sorensen, AG (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, 13th St,Bldg 149 MC 2301, Boston, MA 02129 USA. EM sorensen@nmr.mgh.harvard.edu NR 6 TC 3 Z9 3 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 2010 VL 257 IS 2 BP 303 EP 304 DI 10.1148/radiol.101691 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 667IZ UT WOS:000283187800001 PM 20959541 ER PT J AU Choy, G Pomerantz, SR AF Choy, Garry Pomerantz, Stuart R. TI Net Assets: Online Services for Transmitting Files Too Large to E-mail SO RADIOLOGY LA English DT Editorial Material C1 [Pomerantz, Stuart R.] Massachusetts Gen Hosp, Dept Neuroradiol, Boston, MA 02114 USA. [Choy, Garry] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Pomerantz, SR (reprint author), Massachusetts Gen Hosp, Dept Neuroradiol, 55 Fruit St, Boston, MA 02114 USA. EM netassets@rsna.org NR 0 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 2010 VL 257 IS 2 BP 315 EP 317 DI 10.1148/radiol.10101196 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 667IZ UT WOS:000283187800006 ER PT J AU Singh, S Kalra, MK Hsieh, JA Licato, PE Do, S Pien, HH Blake, MA AF Singh, Sarabjeet Kalra, Mannudeep K. Hsieh, Jiang Licato, Paul E. Do, Synho Pien, Homer H. Blake, Michael A. TI Abdominal CT: Comparison of Adaptive Statistical Iterative and Filtered Back Projection Reconstruction Techniques SO RADIOLOGY LA English DT Article ID RAY COMPUTED-TOMOGRAPHY; DOSE REDUCTION; IMAGE QUALITY; NOISE; ALGORITHMS; ARTIFACTS; EMISSION; PATIENT; NUMBER; HEAD AB Purpose: To compare image quality and lesion conspicuity on abdominal computed tomographic (CT) images acquired with different x-ray tube current-time products (50-200 mAs) and reconstructed with adaptive statistical iterative reconstruction (ASIR) and filtered back projection (FBP) techniques. Materials and Methods: Twenty-two patients (mean age, 60.1 years +/- 7.3 [standard deviation]; age range, 52.8-67.4 years; mean weight, 78.9 kg +/- 18.3; 12 men, 10 women) gave informed consent for this prospective institutional review board-approved and HIPAA-compliant study, which involved the acquisition of four additional image series at multidetector CT. Images were acquired at different tube current-time products (200, 150, 100, and 50 mAs) and encompassed an abdominal lesion over a 10-cm scan length. Images were reconstructed separately with FBP and with three levels of ASIR-FBP blending. Two radiologists reviewed FBP and ASIR images for image quality in a blinded and randomized manner. Volume CT dose index (CTDI(vol)), dose-length product, patient weight, objective noise, and CT numbers were recorded. Data were analyzed by using analysis of variance and the Wilcoxon signed rank test. Results: CTDI vol values were 16.8, 12.6, 8.4, and 4.2 mGy for 200, 150, 100, and 50 mAs, respectively (P < .001). Subjective noise was graded as below average at 150 mAs and average at 100 and 50 mAs for ASIR images, as compared with FBP images, on which noise was graded as average at 150 mAs, above average at 100 mAs, and unacceptable at 50 mAs. A substantial blotchy image appearance was noted in four of 22 image series acquired at 4.2 mGy with 70% ASIR. Lesion conspicuity was significantly better at 4.2 mGy on ASIR than on FBP images (observed P < .044), and overall diagnostic confidence changed from unacceptable on FBP to acceptable on ASIR images. Conclusion: ASIR lowers noise and improves diagnostic confidence in and conspicuity of subtle abdominal lesions at 8.4 mGy when images are reconstructed with 30% ASIR blending and at 4.2 mGy in patients weighing 90 kg or less when images are reconstructed with 50% or 70% ASIR blending. (C) RSNA, 2010 C1 [Singh, Sarabjeet; Kalra, Mannudeep K.; Do, Synho; Pien, Homer H.; Blake, Michael A.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Hsieh, Jiang; Licato, Paul E.] GE Healthcare, Waukesha, WI USA. RP Singh, S (reprint author), Massachusetts Gen Hosp, Dept Radiol, 25 New Chardon St,Suite 400B, Boston, MA 02114 USA. EM ssingh6@partners.org NR 25 TC 209 Z9 233 U1 5 U2 21 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 2010 VL 257 IS 2 BP 373 EP 383 DI 10.1148/radiol.10092212 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 667IZ UT WOS:000283187800013 PM 20829535 ER PT J AU Liu, SS Togioka, BM Hurley, RW Vu, CM Hanna, MN Murphy, JD Wu, CL AF Liu, Spencer S. Togioka, Brandon M. Hurley, Robert W. Vu, Cuong M. Hanna, Marie N. Murphy, Jamie D. Wu, Christopher L. TI Methodological Quality of Randomized Controlled Trials of Postoperative Epidural Analgesia Validation of the Epidural Analgesia Trial Checklist as a Specific Instrument to Evaluate Methodology SO REGIONAL ANESTHESIA AND PAIN MEDICINE LA English DT Review ID REGIONAL-ANESTHESIA; CLINICAL-TRIALS; PATIENT; METAANALYSES; SURGERY; EFFICACY AB Background: The overall benefits of epidural analgesia are controversial, in part because of the varying quality of methodology in published randomized controlled trials (RCTs). We performed a systematic review of available RCTs to examine the methodological quality of epidural analgesia trials. Current instruments for evaluating the quality of methodology are generic; thus, we also developed a specific assessment tool named Epidural Analgesia Trial Checklist (EATC). Methods: The National Library of Medicine's PubMed database was searched (1966 to January 2006) for RCTs of epidural analgesia. All RCTs that had epidural infusion analgesia in at least 1 study arm and as primary intervention for randomization were included. Two independent reviewers were given blinded full-text paper versions of each article and reviewed all articles for inclusion in this study. Study characteristics were extracted from accepted RCTs, and reviewers completed the standardized 7-item Jadad score, 22-item Consolidated Standards of Reporting Trials (CONSORT) checklist, and 8-item EATC for evaluation of methodological quality. Results: A total of 321 articles met all inclusion criteria. The overall median (first, third quartiles) Jadad, CONSORT, and EATC scores were 2 (1, 3), 10(8, 11), and 4 (3, 6) (of maximum scores of 5, 22, and 8), respectively. For all assessments, we found significantly higher methodological study quality for articles with a larger study population size, those written by a first author affiliated with an anesthesiology department, and studies published after release of the CONSORT statement with a significant overall increase in methodological quality over time. There was no effect on methodological quality with regard to region of publication or number of centers. There was relatively high interrater agreement when using the EATC (kappa = 0.92). The items most frequently lacking from the studies captured using the EATC were appropriate description/definition of adverse effects (11.8% of all studies properly reported this), proper presentation of visual analog scale (VAS) pain scores (31.2%), and assessment of VAS pain both at rest and with activity (39.9%). Conclusions: Methodology scores for epidural analgesia RCTs have improved over time. The EATC seems to correlate well with other commonly used generic assessments for methodological RCT quality and be useful for assessing methodological quality of epidural RCTs. Future epidural analgesia RCTs should focus on improving appropriate description/definition of adverse effects, proper presentation of VAS pain scores, and assessment of VAS pain both at rest and with activity. C1 [Liu, Spencer S.] Hosp Special Surg, Dept Anesthesiol, New York, NY 10021 USA. [Liu, Spencer S.] Cornell Weill Med Ctr, New York, NY USA. [Togioka, Brandon M.; Hanna, Marie N.; Murphy, Jamie D.; Wu, Christopher L.] Johns Hopkins Univ, Dept Anesthesiol & Crit Care Med, Baltimore, MD USA. [Hurley, Robert W.] Univ Florida, Sch Med, Dept Anesthesiol, Gainesville, FL USA. [Vu, Cuong M.] Massachusetts Gen Hosp, Dept Anesthesia, Boston, MA 02114 USA. RP Wu, CL (reprint author), Johns Hopkins Univ Hosp, Carnegie 280,600 N Wolfe St, Baltimore, MD 21287 USA. EM chwu@jhmi.edu FU Department of Anesthesiology and Critical Care Medicine, The Johns Hopkins University, Baltimore, MD FX This work was supported by and should be attributed to the Department of Anesthesiology and Critical Care Medicine, The Johns Hopkins University, Baltimore, MD. NR 25 TC 7 Z9 7 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1098-7339 J9 REGION ANESTH PAIN M JI Region. Anesth. Pain Med. PD NOV-DEC PY 2010 VL 35 IS 6 BP 549 EP 555 DI 10.1097/AAP.0b013e3181fa114e PG 7 WC Anesthesiology SC Anesthesiology GA 681HF UT WOS:000284301300015 PM 20975473 ER PT J AU Gu, AH Ji, GX Zhou, Y Long, Y Shi, XG Fu, GB Wang, SL Song, L Wang, XR AF Gu, Aihua Ji, Guixiang Zhou, Yong Long, Yan Shi, Xiangguo Fu, Guangbo Wang, Shoulin Song, Ling Wang, Xinru TI Polymorphisms of nucleotide-excision repair genes may contribute to sperm DNA fragmentation and male infertility SO REPRODUCTIVE BIOMEDICINE ONLINE LA English DT Article DE male infertility; nucleotide-excision repair (NER); polymorphisms; sperm DNA damage; xeroderma pigmentosum group A gene (XPA) ID PIGMENTOSUM GROUP-A; LUNG-CANCER RISK; BREAST-CANCER; CAPACITY; SMOKING; XPA; ASSOCIATION; SPERMATOZOA; FERTILITY; QUALITY AB The nucleotide-excision repair (NER) system is crucial for the removal of bulky DNA adducts during spermatogenesis. Dysfunction of its repair capacity is likely related to the increased susceptibility to DNA damage. In this study, four polymorphisms in NER pathway (XPA(-4) G/A, ERCC1 C8092A, XPD Lys751Gln and XPF Ser835Ser) were selected to evaluate their potential impact on sperm DNA damage and male infertility. Genotypes were determined by PCR-restriction fragment length polymorphism. Sperm DNA damage was evaluated by TdT-mediated dUDP nick-end labelling assay. A case-only study of 620 infertile men found a significant association between XPA(-4) G/A polymorphism and sperm DNA damage. Individuals with the XPA(-4) A allele showed more sperm DNA damage and lower sperm concentration than G allele carriers. Further analysis, including 620 patients and 385 controls, revealed a 1.52-fold risk (95% CI 1.08-2.02) of developing male infertility in the XPA(-4) AA carriers compared with noncarriers. Luciferase assay verified that the promoter with the XPA(-4) A allele had a lower transcriptional activity than that with the G allele. These data provide the first evidence that 4 G/A polymorphism in XPA promoter alters its transcriptional activity and, thus, might contribute to sperm DNA damage and male infertility. Online (C) 2010, Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved. C1 [Gu, Aihua; Ji, Guixiang; Long, Yan; Shi, Xiangguo; Wang, Shoulin; Song, Ling; Wang, Xinru] Nanjing Med Univ, Key Lab Reprod Med, Inst Toxicol, Nanjing 210029, Peoples R China. [Zhou, Yong] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. [Fu, Guangbo] Nanjing Med Univ, Huai An Affiliated Hosp 1, Dept Urol, Huaian, Peoples R China. RP Wang, XR (reprint author), Nanjing Med Univ, Key Lab Reprod Med, Inst Toxicol, Nanjing 210029, Peoples R China. EM xrwang@njmu.edu.cn FU National Basic Research Program of China (973 Program) [2009CB941703]; National Science Foundation of China [30901210]; Natural Science Foundation of Jiangsu Province [BK2009422]; PCSIRT [IRT0631]; Natural Science Foundation of the Jiangsu Higher Education Institutions of China [09KJB330002] FX The authors thank YY Wei for the statistical analysis. This work was supported by the National Basic Research Program of China (973 Program, grant no. 2009CB941703), the National Science Foundation of China (grant no. 30901210), the Natural Science Foundation of Jiangsu Province (grant no. BK2009422), PCSIRT, IRT0631 and the Natural Science Foundation of the Jiangsu Higher Education Institutions of China (grant no. 09KJB330002). NR 45 TC 6 Z9 7 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1472-6483 EI 1472-6491 J9 REPROD BIOMED ONLINE JI Reprod. Biomed. Online PD NOV PY 2010 VL 21 IS 5 BP 602 EP 609 DI 10.1016/j.rbmo.2010.06.025 PG 8 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 687SA UT WOS:000284797000005 PM 20864414 ER PT J AU Li, HK Florez-Arango, JF Hubbard, LD Esquivel, A Danis, RP Krupinski, EA AF Li, Helen K. Florez-Arango, Jose F. Hubbard, Larry D. Esquivel, Adol Danis, Ronald P. Krupinski, Elizabeth A. TI GRADING DIABETIC RETINOPATHY SEVERITY FROM COMPRESSED DIGITAL RETINAL IMAGES COMPARED WITH UNCOMPRESSED IMAGES AND FILM SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES LA English DT Article DE classification; diabetic retinopathy; digital; film; fundus photography; image compression; JND; JPEG2000; just-noticeable difference; reproducibility; telemedicine ID VISUAL-SYSTEM MODEL; COPY MAMMOGRAPHY DISPLAY; OBSERVER PERFORMANCE; PHOTOGRAPHY; DIAGNOSIS; JPEG; TELEOPHTHALMOLOGY; TELEMEDICINE; CRT AB Purpose: To compare research grading of diabetic retinopathy (DR) severity level from compressed digital images versus uncompressed images and film. Methods: Compressed (JPEG2000, 37:1) digital images (C) were compared with uncompressed digital (U) and film (F) stereoscopic photographs from a 152-eye cohort with full-spectrum Early Treatment Diabetic Retinopathy Study severity levels for agreement on severity level, DR presence with ascending severity threshold, presence of DR index lesions, and repeatability of grading. Results: Classification of Early Treatment Diabetic Retinopathy Study severity levels from C images agreed substantially with results from F images (kappa = 0.60, kappa(w) [linear weighted] = 0.86) and uncompressed digital images (kappa = 0.76, kappa(w) = 0.92). For agreement of uncompressed digital versus F images, kappa = 0.62 and kappa(w) = 0.86. Distribution of Early Treatment Diabetic Retinopathy Study levels was not significantly different between C and F images (P = 0.09, Bhapkar's test for marginal homogeneity). For presence/absence of DR at 8 ascending severity thresholds, agreement between C and F was "almost perfect'' (kappa >= 0.8). Agreement on severity level between readers with C images was at least as good as that with uncompressed digital image or F. Repeatability of severity threshold grading between readers was similar using C or F images. For identifying individual DR lesions, agreement between C and F ranged from "moderate'' to "perfect.'' Agreement of grading venous beading from C was slightly lower than from F. Conclusion: Full Early Treatment Diabetic Retinopathy Study scale DR severity level grading using C images is comparable to that using U images or film. RETINA 30:1651-1661, 2010 C1 [Li, Helen K.] Thomas Jefferson Univ, Dept Ophthalmol, Philadelphia, PA 19107 USA. [Li, Helen K.; Florez-Arango, Jose F.] Univ Texas Hlth Sci Ctr, Sch Biomed Informat, Houston, TX USA. [Florez-Arango, Jose F.] Univ Antioquia, Sch Med, Medellin, Colombia. [Hubbard, Larry D.; Danis, Ronald P.] Univ Wisconsin, Dept Ophthalmol & Visual Sci, Madison, WI USA. [Esquivel, Adol] Baylor Coll Med, Houston Vet Affairs Med Ctr, Houston, TX 77030 USA. [Krupinski, Elizabeth A.] Univ Arizona, Dept Radiol, Tucson, AZ 85724 USA. RP Li, HK (reprint author), Univ Texas Med Branch, Dept Ophthalmol & Visual Sci, 301 Univ Blvd, Galveston, TX 77555 USA. EM hlimed@mac.com OI Florez-Arango, Jose F/0000-0001-9083-0195 FU Juvenile Diabetes Foundation Research International, New York, NY; Research to Prevent Blindness FX Supported by a grant from Juvenile Diabetes Foundation Research International, New York, NY (H.K.L.) and by unrestricted grants from the Research to Prevent Blindness (Department of Ophthalmology and Visual Sciences, The University of Texas Medical Branch and the Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health). NR 42 TC 5 Z9 5 U1 0 U2 1 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 2010 VL 30 IS 10 BP 1651 EP 1661 DI 10.1097/IAE.0b013e3181e3790b PG 11 WC Ophthalmology SC Ophthalmology GA 678HL UT WOS:000284064600014 PM 20921928 ER PT J AU Cruz-Gonzalez, I Diaz, TA Inglessis-Azuaje, I Palacios, IF AF Cruz-Gonzalez, Ignacio Diaz, Tulio A. Inglessis-Azuaje, Ignacio Palacios, Igor F. TI Use of a Second Device for the Closure of Patent Foramen Ovale SO REVISTA ESPANOLA DE CARDIOLOGIA LA Spanish DT Letter ID PERCUTANEOUS CLOSURE; PARADOXICAL EMBOLISM C1 [Cruz-Gonzalez, Ignacio] Hosp Univ Salamanca, Serv Cardiol, Salamanca, Spain. [Cruz-Gonzalez, Ignacio; Diaz, Tulio A.; Inglessis-Azuaje, Ignacio; Palacios, Igor F.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Serv Cardiol, Boston, MA USA. RP Cruz-Gonzalez, I (reprint author), Hosp Univ Salamanca, Serv Cardiol, Salamanca, Spain. RI IBSAL, Secretaria/H-3719-2011 NR 5 TC 0 Z9 0 U1 0 U2 0 PU EDICIONES DOYMA S A PI BARCELONA PA TRAV DE GRACIA 17-21, 08021 BARCELONA, SPAIN SN 0300-8932 J9 REV ESP CARDIOL JI Rev. Esp. Cardiol. PD NOV PY 2010 VL 63 IS 11 BP 1384 EP 1386 DI 10.1016/S0300-8932(10)70311-0 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 672DI UT WOS:000283562800021 PM 21070737 ER PT J AU Andreassen, M Frystyk, J Miller, KK Kristensen, LO AF Andreassen, Mikkel Frystyk, Jan Miller, Karen K. Kristensen, Lars O. TI Interferon-beta treatment associated with a biochemical profile suggestive of acromegaly. A case report of a patient treated for multiple sclerosis SO SCANDINAVIAN JOURNAL OF CLINICAL & LABORATORY INVESTIGATION LA English DT Article DE Multiple sclerosis; interferon-beta treatment; growth hormone; insulin-like growth factor-I; insulin-like growth factor I receptor ID GROWTH-FACTOR-I; DISEASE; SERUM AB We describe a 34-year-old female treated with IFN-beta for 8 years with a biochemical profile suggestive of acromegaly. The patient presented with elevated serum insulin-like growth factor-I (IGF-I) and insufficient suppression of growth hormone (GH) during oral glucose tolerance test (OGTT). There were no clinical features of acromegaly. A 5-day profile showed higher GH levels on the 3 days following IFN-beta injections. Total and bioactive IGF-I were also elevated but did not fluctuate. Four weeks off IFN-beta normalized suppression of GH during OGTT but did not reduce serum IGF-I or bioactive IGF-I. In conclusion, IFN-beta treatment mimicked acromegaly biochemically. The changes were partially reversible. C1 [Andreassen, Mikkel; Kristensen, Lars O.] Univ Copenhagen, Herlev Hosp, Endocrine Unit, Dept Internal Med O,Lab Endocrinol, DK-2730 Herlev, Denmark. [Frystyk, Jan] Aarhus Univ Hosp, Med Res Labs, Inst Clin, DK-8000 Aarhus C, Denmark. [Frystyk, Jan] Aarhus Univ Hosp, Med Dept M, DK-8000 Aarhus C, Denmark. [Miller, Karen K.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Neuroendocrine Unit,Dept Med, Boston, MA 02115 USA. RP Andreassen, M (reprint author), Univ Copenhagen, Herlev Hosp, Endocrine Unit, Dept Internal Med O,Lab Endocrinol, Herlev Ringvej 75, DK-2730 Herlev, Denmark. EM andreassenmikkel@hotmail.com FU NHLBI NIH HHS [K24 HL092902] NR 15 TC 3 Z9 3 U1 0 U2 0 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0036-5513 EI 1502-7686 J9 SCAND J CLIN LAB INV JI Scand. J. Clin. Lab. Invest. PD NOV PY 2010 VL 70 IS 7 BP 519 EP 522 DI 10.3109/00365513.2010.521256 PG 4 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 666PB UT WOS:000283127000009 PM 20873969 ER PT J AU Wylie, KP Tregellas, JR AF Wylie, Korey P. Tregellas, Jason R. TI The role of the insula in schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Review DE Insula; Schizophrenia; Neuroimaging; Faces; Prosody; Acetylcholine ID AUDITORY-VERBAL HALLUCINATIONS; FUNCTIONAL MAGNETIC-RESONANCE; MATTER VOLUME ABNORMALITIES; FACIAL AFFECT RECOGNITION; VOXEL-BASED MORPHOMETRY; SELF-FACE RECOGNITION; COMMON NEURAL BASIS; OLD-WORLD MONKEY; HUMAN BRAIN; EMOTIONAL PROSODY AB Involvement of the insular cortex is a common finding in neuroanatomical studies of schizophrenia, yet its contribution to disease pathology remains unknown. This review describes the normal function of the insula and examines pathology of this region in schizophrenia. The insula is a cortical structure with extensive connections to many areas of the cortex and limbic system. It integrates external sensory input with the limbic system and is integral to the awareness of the body's state (interoception). Many deficits observed in schizophrenia involve these functions and may relate to insula pathology. Furthermore, reports describing deficits caused by lesions of the insula parallel deficits observed in schizophrenia. Examples of insula-related functions that are altered in schizophrenia include the processing of both visual and auditory emotional information, pain, and neuronal representations of the self. The last of these functions, processing representations of the self, plays a key role in discriminating between self-generated and external information, suggesting that insula dysfunction may contribute to hallucinations, a cardinal feature of schizophrenia. Published by Elsevier B.V. C1 [Wylie, Korey P.; Tregellas, Jason R.] Univ Colorado, Dept Psychiat, Aurora, CO 80045 USA. [Tregellas, Jason R.] Denver VA Med Ctr, Res Serv, Denver, CO 80220 USA. RP Tregellas, JR (reprint author), Univ Colorado Denver, Dept Psychiat, Mail Stop F546,13001 E 17th Pl, Aurora, CO 80045 USA. EM Jason.Tregellas@ucdenver.edu RI Tregellas, Jason/J-3637-2015 FU NIMH NIH HHS [P50 MH086383] NR 166 TC 93 Z9 94 U1 7 U2 25 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD NOV PY 2010 VL 123 IS 2-3 BP 93 EP 104 DI 10.1016/j.schres.2010.08.027 PG 12 WC Psychiatry SC Psychiatry GA 687RN UT WOS:000284795700001 PM 20832997 ER PT J AU Kikinis, Z Fallon, JH Niznikiewicz, M Nestor, P Davidson, C Bobrow, L Pelavin, PE Fischl, B Yendiki, A McCarley, RW Kikinis, R Kubicki, M Shenton, ME AF Kikinis, Z. Fallon, J. H. Niznikiewicz, M. Nestor, P. Davidson, C. Bobrow, L. Pelavin, P. E. Fischl, B. Yendiki, A. McCarley, R. W. Kikinis, R. Kubicki, M. Shenton, M. E. TI Gray matter volume reduction in rostral middle frontal gyrus in patients with chronic schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE Schizophrenia; Magnetic resonance imaging; Middle frontal gyrus; Dorsal lateral prefrontal cortex; Working memory ID HUMAN CEREBRAL-CORTEX; DORSOLATERAL PREFRONTAL CORTEX; SURFACE-BASED ANALYSIS; WORKING-MEMORY; COORDINATE SYSTEM; CORTICAL SURFACE; MRI; PARCELLATION; METAANALYSIS; VARIABILITY AB The dorsolateral prefrontal cortex (DLPFC) is a brain region that has figured prominently in studies of schizophrenia and working memory, yet the exact neuroanatomical localization of this brain region remains to be defined. DLPFC primarily involves the superior frontal gyrus and middle frontal gyrus (MFG). The latter, however is not a single neuroanatomical entity but instead is comprised of rostral (anterior, middle, and posterior) and caudal regions. In this study we used structural MRI to develop a method for parcellating MFG into its component parts. We focused on this region of DLPFC because it includes BA46, a region involved in working memory. We evaluated volume differences in MFG in 20 patients with chronic schizophrenia and 20 healthy controls. Mid-rostral MFG (MR-MFG) was delineated within the rostra! MFG using anterior and posterior neuroanatomical landmarks derived from cytoarchitectonic definitions of BA46. Gray matter volumes of MR-MFG were then compared between groups, and a significant reduction in gray matter volume was observed (p < 0.008), but not in other areas of MFG (i.e., anterior or posterior rostra! MFG, or caudal regions of MFG). Our results demonstrate that volumetric alterations in MFG gray matter are localized exclusively to MR-MFG. 3D reconstructions of the cortical surface made it possible to follow MFG into its anterior part, where other approaches have failed. This method of parcellation offers a more precise way of measuring MR-MFG that will likely be important in further documentation of DLPFC anomalies in schizophrenia. (C) 2010 Elsevier B.V. All rights reserved. C1 [Kikinis, Z.; Davidson, C.; Bobrow, L.; Pelavin, P. E.; Kubicki, M.; Shenton, M. E.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Psychiat Neuroimaging Lab,Dept Psychiat, Boston, MA 02215 USA. [Fallon, J. H.] Univ Calif Irvine, Dept Psychiat & Human Behav, Irvine, CA 92717 USA. [Niznikiewicz, M.; Nestor, P.; McCarley, R. W.; Kubicki, M.; Shenton, M. E.] Harvard Univ, Med Sch Brockton, Clin Neurosci Div, Neurosci Lab,Dept Psychiat,VA Boston Healthcare S, Boston, MA USA. [Nestor, P.] Univ Massachusetts, Dept Psychol, Boston, MA 02125 USA. [Fischl, B.; Yendiki, A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Kikinis, R.; Shenton, M. E.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Surg Planning Lab,Dept Radiol, Boston, MA 02215 USA. [Fischl, B.] MIT, CSAIL HST, Cambridge, MA 02139 USA. RP Kikinis, Z (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Psychiat Neuroimaging Lab,Dept Psychiat, 1249 Boylston St,3rd Floor, Boston, MA 02215 USA. EM zora@bwh.harvard.edu RI McCarley, Robert/N-5562-2014 OI McCarley, Robert/0000-0001-5705-7495 FU NARSAD; Department of Veterans Affairs; VA Schizophrenia Center; National Institute of Mental Health [R01 MH 50747, K05 MR 070047, R01 MH 40799, R01 MH 052807]; NIH Mental Health Centers for Interventional Development and Applied Research-CIDAR [P50 MH 080272]; National Alliance for Medical Image Computing (NAMIC) [U54 EB005149]; NCIGT [P41 RR 019703]; Neuroimage Analysis Center (NAC) [P41 RR 13218] FX This work was supported, in part, by a NARSAD Young Investigator Award (ZK), by the Department of Veterans Affairs Merit Awards (MES, RWM), by a VA Schizophrenia Center (RWM, MES), by grants from the National Institute of Mental Health including a Career Reentry Supplement (ZK) on R01 MH 50747 (MES), a K05 MR 070047 (MES), an R01 MH 40799 and R01 MH 052807 (RWM), and a NIH Mental Health Centers for Interventional Development and Applied Research-CIDAR - P50 MH 080272 (RWM, also MES, MK), and, finally, by grants from the National Alliance for Medical Image Computing (NAMIC - U54 EB005149 (RK, also MK, MES), NCIGT P41 RR 019703 (RK) and a Neuroimage Analysis Center (NAC) P41 RR 13218 (RK). The authors gratefully acknowledge the support of Francisco Romo, M.D. and Brain Healy, PhD, for his assistance on the statistical analyses. NR 40 TC 24 Z9 24 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD NOV PY 2010 VL 123 IS 2-3 BP 153 EP 159 DI 10.1016/j.schres.2010.07.027 PG 7 WC Psychiatry SC Psychiatry GA 687RN UT WOS:000284795700007 PM 20822884 ER PT J AU Lim, D Oliva, E AF Lim, Diana Oliva, Esther TI Nonendometrioid endometrial carcinomas SO SEMINARS IN DIAGNOSTIC PATHOLOGY LA English DT Article DE Carcinoma; Serous; Clear cell; Squamous cell; Transitional cell; Neuroendocrine; Undifferentiated; Endometrium ID PAPILLARY SEROUS CARCINOMA; CLEAR-CELL-CARCINOMA; OF-THE-LITERATURE; SMOOTH-MUSCLE TUMORS; FEMALE GENITAL-TRACT; GENE-EXPRESSION PROFILES; SOFT-PART SARCOMA; INVASIVE MICROPAPILLARY CARCINOMA; DIFFERENT HISTOLOGIC TYPES; E-CADHERIN EXPRESSION AB Clinicopathologic studies support a classification of endometrial carcinoma into two main categories (type I and type II). Type I cancers consist of endometrioid and mucinous carcinomas, with the former being the most common, whereas serous and clear cell carcinomas are the so-called "prototype" of type II cancers. Nonendometrioid carcinomas account for approximately 10% of endometrial carcinomas and differ from endometrioid carcinomas in terms of patient demographics, morphologic features, and biological behavior. Molecular studies have provided further insights into the differing alterations involved in the development and progression of these tumors. This review summarizes the characteristic clinical, morphologic, immunophenotypic, and molecular features of the various subtypes of nonendometrioid carcinomas and also highlights relevant conditions (both nonneoplastic and neoplastic) that should be considered in the differential diagnosis of these tumors. (C) 2010 Elsevier Inc. All rights reserved. C1 [Lim, Diana; Oliva, Esther] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Oliva, E (reprint author), Massachusetts Gen Hosp, Dept Pathol Warren 2, 55 Fruit St, Boston, MA 02114 USA. EM eoliva@partners.org NR 230 TC 10 Z9 10 U1 2 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 0740-2570 EI 1930-1111 J9 SEMIN DIAGN PATHOL JI Semin. Diagn. Pathol. PD NOV PY 2010 VL 27 IS 4 BP 241 EP 260 DI 10.1053/j.semdp.2010.09.004 PG 20 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 701EV UT WOS:000285798000005 PM 21309259 ER PT J AU Humphreys, BD AF Humphreys, Benjamin D. TI Onco-Nephrology: Kidney Disease in the Cancer Patient: Introduction SO SEMINARS IN NEPHROLOGY LA English DT Editorial Material ID CELL TRANSPLANTATION; PREECLAMPSIA; HYPERTENSION; PROTEINURIA; ASSOCIATION; RISK C1 Brigham & Womens Hosp, Div Renal, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Humphreys, BD (reprint author), Brigham & Womens Hosp, Div Renal, Dana Farber Canc Inst, Boston, MA 02115 USA. FU NIDDK NIH HHS [K08 DK073628, K08 DK073628-04, K08 DK073628-04S1, R01 DK088923, R01 DK088923-01] NR 13 TC 4 Z9 6 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 2010 VL 30 IS 6 BP 531 EP 533 DI 10.1016/j.semnephrol.2010.09.001 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 702NH UT WOS:000285900900001 PM 21146118 ER PT J AU Robinson, ES Khankin, EV Karumanchi, SA Humphreys, BD AF Robinson, Emily S. Khankin, Eliyahu V. Karumanchi, S. Ananth Humphreys, Benjamin D. TI Hypertension Induced by Vascular Endothelial Growth Factor Signaling Pathway Inhibition: Mechanisms and Potential Use as a Biomarker SO SEMINARS IN NEPHROLOGY LA English DT Review DE VEGF; targeted therapy; hypertension; nitric oxide; thrombotic microangiopathy ID BLOOD-PRESSURE; ANGIOGENESIS INHIBITOR; ARTERIAL-HYPERTENSION; PERMEABILITY FACTOR; TYROSINE KINASE-1; CLINICAL BENEFIT; PROTEIN-KINASE; CELLS SECRETE; VEGF; PREECLAMPSIA C1 [Robinson, Emily S.; Humphreys, Benjamin D.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Khankin, Eliyahu V.; Karumanchi, S. Ananth] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Karumanchi, S. Ananth] Howard Hughes Med Inst, Chevy Chase, MD USA. [Humphreys, Benjamin D.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Humphreys, BD (reprint author), Harvard Univ, Inst Med, Room 550,4 Blackfan Circle, Boston, MA 02115 USA. EM bhumphreys@partners.org RI Khankin, Eli/M-7648-2013 FU National Institutes of Health [DK073628, DK084316, UL1 RR 025758-02]; Harvard Catalyst; National Kidney Foundation FX This work was supported by National Institutes of Health grants DK073628 and DK084316, and a pilot grant from Harvard Catalyst: National Institutes of Health grant UL1 RR 025758-02, with financial contributions from participating institutions (all to B.D.H.), and a grant from the National Kidney Foundation (E.S.R.). S.A.K. is listed as a co-inventor on multiple patents held by the Beth Israel Deaconess Medical Center for the diagnosis Id therapy of preeclampsia. These patents have been nonexclusively licensed to multiple companies. S.A.K. is a consultant to Beckman Coulter, Johnson & Johnson, Roche, and Abbott Diagnostics, which are developing biomarkers for preeclampsia diagnosis/prediction. NR 55 TC 46 Z9 46 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 0270-9295 J9 SEMIN NEPHROL JI Semin. Nephrol. PD NOV PY 2010 VL 30 IS 6 BP 591 EP 601 DI 10.1016/j.semnephrol.2010.09.007 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA 702NH UT WOS:000285900900007 PM 21146124 ER PT J AU Heher, EC Spitzer, TR AF Heher, Eliot C. Spitzer, Thomas R. TI Hematopoietic Stem Cell Transplantation in Patients With Chronic Kidney Disease SO SEMINARS IN NEPHROLOGY LA English DT Review DE Hematopoietic stem cell transplantation; chronic kidney disease; conditioning myeloma ID BONE-MARROW-TRANSPLANTATION; TOTAL-BODY IRRADIATION; STAGE RENAL-DISEASE; MIXED LYMPHOHEMATOPOIETIC CHIMERISM; DOSE INTRAVENOUS MELPHALAN; GLOMERULAR-FILTRATION-RATE; TERM-FOLLOW-UP; MULTIPLE-MYELOMA; MYCOPHENOLATE-MOFETIL; APLASTIC-ANEMIA C1 [Heher, Eliot C.] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA. [Heher, Eliot C.; Spitzer, Thomas R.] Massachusetts Gen Hosp, Transplantat Ctr, Boston, MA 02114 USA. [Spitzer, Thomas R.] Massachusetts Gen Hosp, Div Hematol & Oncol, Boston, MA 02114 USA. RP Heher, EC (reprint author), Massachusetts Gen Hosp, Div Nephrol, 165 Cambridge St, Boston, MA 02114 USA. EM eheher@partners.org NR 60 TC 8 Z9 8 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 0270-9295 J9 SEMIN NEPHROL JI Semin. Nephrol. PD NOV PY 2010 VL 30 IS 6 BP 602 EP 614 DI 10.1016/j.semnephrol.2010.09.008 PG 13 WC Urology & Nephrology SC Urology & Nephrology GA 702NH UT WOS:000285900900008 PM 21146125 ER PT J AU Chen, LY Reisner, AT Gribok, A Reifman, J AF Chen, Liangyou Reisner, Andrew T. Gribok, Andrei Reifman, Jaques TI IS RESPIRATION-INDUCED VARIATION IN THE PHOTOPLETHYSMOGRAM ASSOCIATED WITH MAJOR HYPOVOLEMIA IN PATIENTS WITH ACUTE TRAUMATIC INJURIES? SO SHOCK LA English DT Article DE PPG waveform variation; hemorrhage; trauma; prehospital care ID PLETHYSMOGRAPHIC WAVE-FORM; PLETH VARIABILITY INDEX; ARTERIAL PULSE PRESSURE; FLUID RESPONSIVENESS; VENTILATED PATIENTS; VITAL SIGN; AMPLITUDE; EPIDEMIOLOGY; ALGORITHMS; SEVERITY AB It has been widely accepted that metrics related to respiration-induced waveform variation (RIWV) of the photoplethysmogram (PPG) have been associated with hypovolemia in mechanically ventilated patients and in controlled laboratory environments. In this retrospective study, we investigated if PPG RIWV metrics have diagnostic value for patients with acute hemorrhagic hypovolemia in the prehospital environment. Photoplethysmogram waveforms and basic vital signs were recorded in trauma patients during prehospital transport. Retrospectively, we used automated algorithms to select patient records with all five basic vital signs and 45 s or longer continuous, clean PPG segments. From these segments, we identified the onset and peak of individual heartbeats and computed waveform variations in the beats' peaks and amplitudes: (1) as the range between the maximum and the minimum (max-min) values and (2) as their interquartile range (IQR). We evaluated their receiver operating characteristic (ROC) curves for major hemorrhage. Separately, we tested whether RIWV metrics have potential independent information beyond basic vital signs by applying multivariate regression. In 344 patients, RIWV max-min yielded areas under the ROC curves (AUCs) not significantly better than a random AUC of 0.50. Respiration-induced waveform variation computed as IQR yielded ROC AUCs of 0.65 (95% confidence interval, 0.54-0.76) and of 0.64 (0.51-0.75), for peak and amplitude measures, respectively. The IQR metrics added independent information to basic vital signs (P < 0.05), but only moderately improved the overall AUC. Photoplethysmogram RIWV measured as IQR is preferable over max-min, and using PPG RIWV may enhance physiologic monitoring of spontaneously breathing patients outside strictly controlled laboratory environments. C1 [Chen, Liangyou; Reisner, Andrew T.; Gribok, Andrei; Reifman, Jaques] USAMRMC, TATRC, ATTN, MCMR TT, Frederick, MD 21702 USA. [Reisner, Andrew T.] Massachusetts Gen Hosp Boston, Dept Emergency Med, Boston, MA USA. RP Reifman, J (reprint author), USAMRMC, TATRC, ATTN, MCMR TT, 2405 Whittier Dr,Suite 200, Frederick, MD 21702 USA. EM jaques.reifman@us.army.mil FU Combat Casualty Care Research Area Directorate of the US Army Medical Research and Materiel Command, Fort Detrick, MD FX This work was partially supported by the Combat Casualty Care Research Area Directorate of the US Army Medical Research and Materiel Command, Fort Detrick, MD. NR 33 TC 9 Z9 9 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1073-2322 J9 SHOCK JI Shock PD NOV PY 2010 VL 34 IS 5 BP 455 EP 460 DI 10.1097/SHK.0b013e3181dc07da PG 6 WC Critical Care Medicine; Hematology; Surgery; Peripheral Vascular Disease SC General & Internal Medicine; Hematology; Surgery; Cardiovascular System & Cardiology GA 667ZU UT WOS:000283238700004 PM 20220568 ER PT J AU Iyer, RS Bhargava, P Medverd, JR AF Iyer, Ramesh S. Bhargava, Puneet Medverd, Jonathan R. TI A 65-year-old man presents with pelvic pain SO SKELETAL RADIOLOGY LA English DT Editorial Material C1 [Bhargava, Puneet; Medverd, Jonathan R.] Univ Washington, Dept Radiol, Body Imaging Sect, Seattle, WA 98108 USA. [Bhargava, Puneet; Medverd, Jonathan R.] VA Puget Sound Hlth Care Syst, Seattle, WA 98108 USA. [Iyer, Ramesh S.] Univ Washington, Med Ctr, Dept Radiol, Seattle, WA 98195 USA. RP Bhargava, P (reprint author), Univ Washington, Dept Radiol, Body Imaging Sect, 1660 S Columbian Way, Seattle, WA 98108 USA. EM bhargp@uw.edu RI Bhargava, Puneet /F-1330-2011; OI Bhargava, Puneet/0000-0002-3849-9666 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-2348 J9 SKELETAL RADIOL JI Skeletal Radiol. PD NOV PY 2010 VL 39 IS 11 BP 1129 EP 1129 DI 10.1007/s00256-010-0898-0 PG 1 WC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging SC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging GA 650PF UT WOS:000281861100011 ER PT J AU Iyer, R Bhargava, P Medverd, J AF Iyer, Ramesh S. Bhargava, Puneet Medverd, Jonathan R. TI A 65-year-old man presents with pelvic pain SO SKELETAL RADIOLOGY LA English DT Editorial Material DE Tophaceous gout; Symphysis pubis ID TOPHACEOUS GOUT; SYMPHYSIS C1 [Bhargava, Puneet; Medverd, Jonathan R.] Univ Washington, Dept Radiol, Seattle, WA 98195 USA. [Bhargava, Puneet; Medverd, Jonathan R.] VA Puget Sound Hlth Care Syst, Seattle, WA 98195 USA. [Iyer, Ramesh S.] Univ Washington, Med Ctr, Dept Radiol, Seattle, WA 98195 USA. RP Bhargava, P (reprint author), Univ Washington, Dept Radiol, 1660 S Columbian Way, Seattle, WA 98195 USA. EM bhargp@uw.edu RI Bhargava, Puneet /F-1330-2011 NR 9 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-2348 J9 SKELETAL RADIOL JI Skeletal Radiol. PD NOV PY 2010 VL 39 IS 11 BP 1151 EP 1152 DI 10.1007/s00256-010-0899-z PG 2 WC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging SC Orthopedics; Radiology, Nuclear Medicine & Medical Imaging GA 650PF UT WOS:000281861100015 PM 20405125 ER PT J AU Wieland, AM Curry, WT Durand, ML Holbrook, EH AF Wieland, Aaron M. Curry, William T. Durand, Marlene L. Holbrook, Eric H. TI Management of a Long-Standing Organic Intracranial Foreign Body SO SKULL BASE-AN INTERDISCIPLINARY APPROACH LA English DT Article DE Skull base; foreign body; cerebrospinal fluid rhinorrhea; endoscopic; meningitis ID CEREBROSPINAL-FLUID LEAKS; BACTERIAL-MENINGITIS; TRANSNASAL; WOOD; AIR; BODIES AB Organic foreign bodies of the skull base are an uncommon problem with the potential for serious morbidity that present complicated treatment dilemmas best managed by a multidisciplinary approach. A 58-year-old male presented to the emergency department with fevers and mental status changes and was found to have bacterial meningitis. Computed tomography of the sinuses revealed two adjacent defects of the ethmoid roof with associated soft tissue density concerning for an encephalocele. He had a remote history of a penetrating left maxilla injury with a stick 13 years earlier. An attempted endoscopic repair of the defects revealed a pulsating splinter of wood emanating from the ethmoid roof defect. Neurosurgery and infectious disease were consulted and several wood fragments were removed endoscopically from the intracranial space. The skull base defects were closed using a septal cartilage underlay and free mucosal overlay graft. The patient has done well in follow-up with no evidence of cerebrospinal fluid leak. Organic foreign bodies from skull base trauma can have a delayed presentation and require a multidisciplinary team approach. In the appropriate setting endoscopic removal is a minimally morbid option. C1 [Wieland, Aaron M.; Holbrook, Eric H.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, Boston, MA 02114 USA. [Wieland, Aaron M.; Holbrook, Eric H.] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02114 USA. [Curry, William T.] Harvard Univ, Sch Med, Dept Neurosurg, Boston, MA 02114 USA. [Durand, Marlene L.] Harvard Univ, Sch Med, Div Infect Dis, Boston, MA 02114 USA. [Curry, William T.; Durand, Marlene L.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Wieland, AM (reprint author), Massachusetts Eye & Ear Infirm, Dept Otolaryngol Head & Neck Surg, 243 Charles St, Boston, MA 02114 USA. EM aaron_wieland@meei.harvard.edu NR 16 TC 0 Z9 2 U1 0 U2 0 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 1531-5010 J9 SKULL BASE-INTERD AP JI Skull Base-Interdiscip. Appr. PD NOV PY 2010 VL 20 IS 6 BP 487 EP 490 DI 10.1055/s-0030-1261264 PG 4 WC Clinical Neurology; Otorhinolaryngology; Surgery SC Neurosciences & Neurology; Otorhinolaryngology; Surgery GA 665UM UT WOS:000283061000016 PM 21772810 ER PT J AU Boyd, JE Katz, EP Link, BG Phelan, JC AF Boyd, Jennifer E. Katz, Emerald P. Link, Bruce G. Phelan, Jo C. TI The relationship of multiple aspects of stigma and personal contact with someone hospitalized for mental illness, in a nationally representative sample SO SOCIAL PSYCHIATRY AND PSYCHIATRIC EPIDEMIOLOGY LA English DT Article DE Stigma; Mental illness; Survey; Personal experience; Contact ID SOCIAL DISTANCE; PERCEIVED STIGMA; PEOPLE; ILL; DISCRIMINATION; CONSEQUENCES; SEVERITY AB The stigma of mental illness has been shown to be affected by personal contact with mental illness and by a belief in the genetic heritability of mental illness. We use data from a nationally representative survey to test whether the relationship of stigma with contact remains after taking into account the effects of genetic beliefs and other background characteristics. Contact was defined as a history of psychiatric hospitalization among respondents themselves, their family members, or their friends. Respondents answered questions about a vignette character with a mental illness. We found that respondents with contact felt less anger and blame toward the character, thought that the character had a more serious problem, and would want less social distance from the character, including both casual and intimate aspects of social distance. Respondents with contact were not significantly different from the general population in the degree to which they expressed sympathy, thought the problem would last a lifetime, or wanted to restrict reproduction. Thus, contact is associated with having a less ostracizing, critical attitude toward a stranger with mental illness. The results underscore the importance of this experienced group as a resource in fighting stigma in society. Since many people who have had a psychiatric hospitalization have not told their friends or family members about it, this lower-stigma group could be enlarged. C1 [Boyd, Jennifer E.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94121 USA. [Katz, Emerald P.] San Francisco VA Med Ctr, Psychosocial Rehabil & Recovery Ctr, San Francisco, CA 94121 USA. [Link, Bruce G.] Columbia Univ, Dept Epidemiol, Mailman Sch Publ Hlth, New York, NY USA. [Link, Bruce G.; Phelan, Jo C.] Columbia Univ, Dept Sociomed Sci, Mailman Sch Publ Hlth, New York, NY USA. [Link, Bruce G.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA. RP Boyd, JE (reprint author), Univ Calif San Francisco, Dept Psychiat, 4150 Clement St 116A, San Francisco, CA 94121 USA. EM jennifer.boyd@ucsf.edu RI Link, Bruce/N-9087-2013; OI Link, Bruce/0000-0001-9980-7450 NR 29 TC 28 Z9 29 U1 3 U2 12 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 0933-7954 J9 SOC PSYCH PSYCH EPID JI Soc. Psychiatry Psychiatr. Epidemiol. PD NOV PY 2010 VL 45 IS 11 BP 1063 EP 1070 DI 10.1007/s00127-009-0147-9 PG 8 WC Psychiatry SC Psychiatry GA 666LY UT WOS:000283117900005 PM 19823756 ER PT J AU Grottkau, BE Rebello, G Merlin, G Winograd, JM AF Grottkau, Brian E. Rebello, Gleeson Merlin, Gabriel Winograd, Jonathan M. TI Coaptive Film Versus Subcuticular Suture Comparing Skin Closure Time After Posterior Spinal Instrumented Fusion in Pediatric Patients With Spinal Deformity SO SPINE LA English DT Article DE scoliosis; kyphosis; spinal deformity; skin closure; time for closure ID WOUND CLOSURE; RANDOMIZED-TRIAL; TISSUE ADHESIVE; SURGERY AB Study Design. A prospective, randomized trial comparing skin closure time between coaptive film and subcuticular Monocryl sutures in children undergoing posterior instrumented spinal fusion. Objective. To prospectively compare skin closure time, complication rate and cosmetic result between coaptive film and subcuticular Monocryl wound closures in pediatric spine surgery. Summary of Background Data. Posterior instrumented spinal fusions for spinal deformity in children are time-consuming ventures that are demanding on both the patient and physician. Minimizing the time for skin closure at the end of prolonged surgery diminishes the physical burden on the surgeon, the operating room personnel, and reduces operating room costs. Methods. Twenty-five children (mean age, 14.1 year) underwent posterior instrumented spinal fusion. Twenty-five incisions in 25 patients (12 closed with 3-0 subcuticular Monocryl sutures, 13 closed with coaptive film [Steri Strip S; 3 M company]) were evaluated. The method of skin closure was randomized before beginning the procedure and the surgeon informed just before skin closure. Closure time was recorded. A blinded plastic surgeon using a visual analogue scale assessed the cosmetic results at a minimum 3-month follow-up. Results. Incisions closed with coaptive film required less time to complete than incisions closed with subcuticular suture. The mean time for skin closure using coaptive film was 290.62 seconds compared to the mean time of 674.75 seconds using Monocryl sutures (P < 0.000001). The average length of incisions closed with coaptive film was similar to the corresponding incisions that were closed with subcuticular Monocryl sutures (30.8 and 34.0 cm, respectively, P = 0.22). There was no significant difference in the cosmetic results or the number of wound complications using either technique. Conclusion. Coaptive film is a time-saving option for skin closure following pediatric spine surgery with comparable cosmetic results and no difference in complication rates. C1 [Grottkau, Brian E.; Rebello, Gleeson; Merlin, Gabriel; Winograd, Jonathan M.] MassGen Hosp Children, Dept Pediat Orthoped, Boston, MA 02114 USA. RP Grottkau, BE (reprint author), MassGen Hosp Children, Dept Pediat Orthoped, 55 Fruit St,YAW 3400, Boston, MA 02114 USA. EM bgrottkau@partners.org FU 3M Corporation FX Supported by 3M Corporation. NR 7 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0362-2436 J9 SPINE JI SPINE PD NOV 1 PY 2010 VL 35 IS 23 BP 2027 EP 2029 DI 10.1097/BRS.0b013e3181c8ad82 PG 3 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 671GX UT WOS:000283490100019 PM 20531072 ER PT J AU Taghavi, CE Lee, KB He, WB Keorochana, G Murray, SS Brochmann, EJ Uludag, H Behnam, K Wang, JC AF Taghavi, Cyrus E. Lee, Kwang-Bok He, Wubing Keorochana, Gun Murray, Samuel S. Brochmann, Elsa J. Uludag, Hasan Behnam, Keyvan Wang, Jeffrey C. TI Bone Morphogenetic Protein Binding Peptide Mechanism and Enhancement of Osteogenic Protein-1 Induced Bone Healing SO SPINE LA English DT Article DE bone morphogenetic protein; bone morphogenetic protein binding peptide; osteogenic protein; bone graft alternative ID ANTERIOR CERVICAL DISKECTOMY; LUMBAR SPINE FUSION; ILIAC-CREST AUTOGRAFT; POLYETHERETHERKETONE SPACER; LIGAMENTUM-FLAVUM; SAFETY PROFILE; MARROW-CELLS; GRAFT; RHBMP-2; MODEL AB Study Design. In vitro and in vivo evaluation of BBP interactions with BMP. Objective. To explore bone morphogenetic protein-binding peptide (BBP)'s mechanism of action, investigate an extended repertoire for BBP applications, and evaluate the usefulness of BBP as a surgical adjuvant when used with recombinant human osteogenic protein-1 (rhOP-1). Summary of Background Data. Bone morphogenetic proteins (BMPs) are osteoinductive proteins that provide a potential alternative to autograft. Their utility is limited by cost, and potential dose-dependent risks, such as local inflammatory reactions and ectopic bone formation. BBP, a cyclized synthetic peptide, avidly binds recombinant human BMP-2 (rhBMP-2) and has been shown to accelerate and enhance its osteogenic qualities. Methods. BBP binding with 4 growth factors from the transforming growth factor -beta family were assessed using surface plasmon resonance. The in vivo retention of rhBMP-2 was quantified by comparing the percentage of retained [(125)I]-labeled rhBMP-2 in absorbable collagen sponge implants with or without BBP at 1, 3, and 7 days postimplantation. The adjunctive effect of BBP with rhOP-1-induced bone growth was evaluated by comparing time to fusion and fusion rates in a rodent posterolateral fusion model with 2 different doses of rhOP-1 with or without BBP. Results. BBP bound all 4 growth factors with an intermediate affinity. The in vivo retention of rhBMP-2 alone ranged from about 40% on day 1 to about 30% on day 7, whereas, the retention of rhBMP-2 in the presence of BBP was about 85% on day 1 and about 55% on day 7. The addition of BBP to rhOP-1 resulted in significantly earlier and greater fusion rates than achieved with rhOP-1 alone. Conclusion. The mechanism of the BBP enhanced osteoinductive properties of BMPs involves the binding and retention of the growth factor, resulting in a prolonged exposure of BMP to the desired fusion site. The use of BBP in conjunction with BMPs may prove to provide satisfactory fusion outcomes, while reducing the costs and side effects associated with BMP use. C1 [Taghavi, Cyrus E.; Lee, Kwang-Bok; He, Wubing; Keorochana, Gun; Wang, Jeffrey C.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Orthopaed Surg, Los Angeles, CA 90095 USA. [Murray, Samuel S.; Brochmann, Elsa J.] VA Greater Los Angeles Hlth Care Syst, Ctr Geriatr Res Educ & Clin, Sepulveda, CA USA. [Murray, Samuel S.; Brochmann, Elsa J.] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. [Murray, Samuel S.] Univ Calif Los Angeles, Interdept Program Biomed Engn, Los Angeles, CA 90024 USA. [Uludag, Hasan] Univ Alberta, Edmonton, AB, Canada. [Behnam, Keyvan] VA Greater Los Angeles Hlth Care Syst, Res Serv, Sepulveda, CA USA. [Behnam, Keyvan] Lanx Inc, Broomfield, CO USA. RP Wang, JC (reprint author), UCLA Comprehens Spine Ctr, Orthopaed Spine Serv, 1250 16th St,Suite 745, Santa Monica, CA 90404 USA. EM jwang@mednet.ucla.edu FU Department of Veterans Affairs, Lanx Inc.; Canadian Institutes of Health Research FX Department of Veterans Affairs, Lanx Inc., and Canadian Institutes of Health Research funds were received in support of this work. Although one or more of the author(s) has/have received or will receive benefits for personal or professional use from a commercial party related directly or indirectly to the subject of this manuscript, benefits will be directed solely to a research fund, foundation, educational institution, or other nonprofit organization which the author(s) has/have been associated. NR 51 TC 17 Z9 18 U1 2 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0362-2436 J9 SPINE JI SPINE PD NOV 1 PY 2010 VL 35 IS 23 BP 2049 EP 2056 DI 10.1097/BRS.0b013e3181cc0220 PG 8 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 671GX UT WOS:000283490100023 PM 20581758 ER PT J AU Stetler, RA Chen, J Cao, GD AF Stetler, R. Anne Chen, Jun Cao, Guodong TI White Matter Protection by Erythropoietin: An Emerging Matter in the Treatment of Neonatal Hypoxic-Ischemic Brain Injury Response SO STROKE LA English DT Letter ID STROKE C1 [Stetler, R. Anne; Chen, Jun; Cao, Guodong] Vet Affairs Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. [Stetler, R. Anne; Chen, Jun; Cao, Guodong] Univ Pittsburgh, Sch Med, Dept Neurol, Pittsburgh, PA 15261 USA. RP Stetler, RA (reprint author), Vet Affairs Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. NR 9 TC 0 Z9 0 U1 1 U2 1 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 2010 VL 41 IS 11 BP E596 EP E596 DI 10.1161/STROKEAHA.110.593574 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 670QX UT WOS:000283443500014 ER PT J AU Pollak, KI Arnold, R Alexander, SC Jeffreys, AS Olsen, MK Abernethy, AP Rodriguez, KL Tulsky, JA AF Pollak, Kathryn I. Arnold, Robert Alexander, Stewart C. Jeffreys, Amy S. Olsen, Maren K. Abernethy, Amy P. Rodriguez, Kari L. Tulsky, James A. TI Do patient attributes predict oncologist empathic responses and patient perceptions of empathy? SO SUPPORTIVE CARE IN CANCER LA English DT Article DE Empathy; Oncologist; Advanced cancer; Socioeconomic status; Negative emotion ID QUALITY-OF-LIFE; PSYCHOLOGICAL ADJUSTMENT; PHYSICIAN COMMUNICATION; CANCER COMMUNICATION; RACIAL-DIFFERENCES; SCOPE TRIAL; INTERVENTION; DISTRUST; PATTERNS; ANXIETY AB Purpose Most patients with advanced cancer experience negative emotion. When patients express emotions, oncologists rarely respond empathically. Oncologists may respond more empathically to some patients, and patients may perceive different levels of empathy and trust given past documentation of disparities in cancer care. Methods We audio-recorded 264 outpatient encounters between oncologists and patients with advanced cancer at three sites. We examined whether patient gender, age, race, marital status, education, economic security, and length of relationship with oncologist were related to oncologist empathic responses to patient's negative emotion and patient's perceptions of oncologist empathy and trust. Results Half (51%) of the patients expressed a negative emotion. Oncologists sometimes responded with empathy (29%). Oncologists were equally empathic with all patients, except they were more empathic with patients with low economic security compared with those reporting high economic security (p=.002). Patients with low economic security viewed oncologists as more empathic (p=.06) compared with those with moderate security. Married patients also viewed oncologists as more empathic (p=.04). Patients who knew their oncologist for more than a year had more trust than patients who knew their oncologists for less time (p=.02). Conclusions Oncologists, in general, did not respond empathically to patient's negative emotion, and did this equally for most patients. Oncologists responded more empathically to patients who were less economically advantaged. In turn, patients with lower economic security perceived more empathy. Although oncologists need more education in responding empathically, they may not need to correct many biases in care. C1 [Pollak, Kathryn I.] Duke Univ, Med Ctr, Dept Community & Family Med, Durham, NC 27710 USA. [Pollak, Kathryn I.; Abernethy, Amy P.; Tulsky, James A.] Duke Univ, Med Ctr, Duke Comprehens Canc Ctr, Canc Prevent Detect & Control Res Program, Durham, NC 27710 USA. [Arnold, Robert; Rodriguez, Kari L.] Univ Pittsburgh, Sch Med, Dept Med, Div Gen Internal Med, Pittsburgh, PA USA. [Arnold, Robert; Rodriguez, Kari L.] Univ Pittsburgh, Sch Med, Inst Doctor Patient Commun, Pittsburgh, PA USA. [Arnold, Robert] Univ Pittsburgh, Sch Med, Inst Enhance Palliat Care, Pittsburgh, PA USA. [Alexander, Stewart C.; Abernethy, Amy P.; Tulsky, James A.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. [Alexander, Stewart C.; Abernethy, Amy P.; Tulsky, James A.] Duke Univ, Med Ctr, Ctr Palliat Care, Durham, NC 27710 USA. [Alexander, Stewart C.; Jeffreys, Amy S.; Olsen, Maren K.; Tulsky, James A.] Durham VA Med Ctr, Ctr Hlth Serv Res, Durham, NC USA. [Olsen, Maren K.] Duke Univ, Med Ctr, Dept Biostat & Bioinformat, Durham, NC 27710 USA. [Rodriguez, Kari L.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Pittsburgh, PA USA. [Rodriguez, Kari L.] VA Pittsburgh Healthcare Syst, Ctr Geriatr Res Educ & Clin, Pittsburgh, PA USA. RP Pollak, KI (reprint author), Duke Univ, Med Ctr, Dept Community & Family Med, Durham, NC 27710 USA. EM kathryn.pollak@duke.edu OI Abernethy, Amy/0000-0001-6930-8722 FU [R01CA100387] FX This work was supported by R01CA100387. The authors have no financial disclosures. NR 29 TC 7 Z9 7 U1 3 U2 13 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0941-4355 J9 SUPPORT CARE CANCER JI Support. Care Cancer PD NOV PY 2010 VL 18 IS 11 BP 1405 EP 1411 DI 10.1007/s00520-009-0762-8 PG 7 WC Oncology; Health Care Sciences & Services; Rehabilitation SC Oncology; Health Care Sciences & Services; Rehabilitation GA 654QG UT WOS:000282182500006 PM 19838742 ER PT J AU Tabbara, M Velmahos, GC Butt, MU Chang, YC Spaniolas, K Demoya, M King, DR Alam, HB AF Tabbara, Malek Velmahos, George C. Butt, Muhammad U. Chang, Yuchiao Spaniolas, Konstantinos deMoya, Marc King, David R. Alam, Hasan B. TI Missed opportunities for primary repair in complicated acute diverticulitis SO SURGERY LA English DT Article ID SIGMOID COLON RESECTION; HINCHEY STAGE-III; PRIMARY ANASTOMOSIS; HARTMANNS PROCEDURE; MANAGEMENT; PERITONITIS; MORBIDITY; INJURIES; SURGERY; DISEASE AB Background. Complicated acute diverticulitis (CAD) requiring an urgent operation is usually managed by fecal diversion (ID) despite reports suggesting that primary repair (PR) is safe. We aim to identify patient characteristics predicting successful PR and explore if patients are managed by ID despite the presence of such characteristics. Methods. We reviewed the medical records of 194 patients with CAD, requiring colectomy within 48 hr of admission from January 1996 to January 2006. Exclusion criteria included: admission for elective repair, treatment with antibiotics and/or per-cutaneous abscess drainage prior to operation (semi-elective), concurrent inflammatory disease, cancer, and inadequate documentation. Univariate and multivariate analysis identified independent predictors of PR. Patients who despite having these independent predictors underwent FD, were compared with the PR group. Results. Eighteen patients (9%) received PR. They were younger than M patients, had a lower incidence of left-sided disease, were less frequently operated on within 4 hr of hospital arrival, and had less severe disease (Hinchey I or II). They also had shorter postoperative hospital stays (6.2 +/- 2.3 vs 14.6 +/- 16.1; P = .002) and a trend towards a lower mortality (0% vs 6.8%; P = .38). The independent predictors of performing PR included: age less than 55 years, interval between admission and operation longer than 4 hr, and a Hinchey score I or II. There were 71 patients who had 2 (64) or all 3 (7) independent predictors of PR but still received FD. These patients were not different in any characteristic from the PR patients but had worse' outcomes. Conclusion. FD remains the prevailing operative method of choice of CAD. Despite the presence of factors favoring PR, many patients still receive FD and have worse outcomes. PR can be used more liberally in CAD. (Surgery 2010; 148 : 919-24.) C1 [Tabbara, Malek; Velmahos, George C.; Butt, Muhammad U.; Chang, Yuchiao; Spaniolas, Konstantinos; deMoya, Marc; King, David R.; Alam, Hasan B.] Harvard Univ, Sch Med, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA USA. [Chang, Yuchiao] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Clin Epidemiol, Boston, MA USA. RP Velmahos, GC (reprint author), 165 Cambridge St,Suite 810, Boston, MA 02114 USA. EM gvelmahos@partners.org OI King, David/0000-0003-1028-1478; Tabbara, Malek/0000-0003-1046-7803 NR 16 TC 10 Z9 10 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 2010 VL 148 IS 5 BP 919 EP 924 DI 10.1016/j.surg.2010.02.015 PG 6 WC Surgery SC Surgery GA 676CP UT WOS:000283888000003 PM 20378139 ER PT J AU Velmahos, GC AF Velmahos, George C. TI Commentary on "Vacuum-assisted closure in severe abdominal sepsis with or without retention sutured sequential fascial closure: A clinical trial" SO SURGERY LA English DT Editorial Material C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, Boston, MA 02114 USA. RP Velmahos, GC (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Surg, 165 Cambridge St,Suite 810, Boston, MA 02114 USA. EM gvelmahos@partners.org NR 2 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 2010 VL 148 IS 5 BP 954 EP 954 DI 10.1016/j.surg.2010.03.027 PG 1 WC Surgery SC Surgery GA 676CP UT WOS:000283888000007 PM 20951863 ER PT J AU Maciejewski, ML Livingston, EH Kahwati, LC Henderson, WG Kavee, AL Arterburn, DE AF Maciejewski, Matthew L. Livingston, Edward H. Kahwati, Leila C. Henderson, William G. Kavee, Andrew L. Arterburn, David E. TI Discontinuation of diabetes and lipid-lowering medications after bariatric surgery at Veterans Affairs medical centers SO SURGERY FOR OBESITY AND RELATED DISEASES LA English DT Article DE Bariatric; Medication; Discontinuation; Diabetes; Dyslipidemia; Veterans ID LAPAROSCOPIC GASTRIC BYPASS; RISK ADJUSTMENT; SURGICAL CARE; OBESITY; COSTS; IMPROVEMENT; QUALITY; EXPENDITURES; METAANALYSIS; PERFORMANCE AB Background: Bariatric surgery has largely been performed on middle-age female populations and been associated with significant medication discontinuation; however, it is unknown whether similar medication discontinuation rates could be achieved in men. The purpose of the present analysis was to examine the discontinuation rate of diabetes or lipid-lowering medications and the patient factors associated with medication discontinuation among veterans undergoing bariatric surgery. Methods: We identified the demographic and health status information for 284 veterans with diabetes and 298 veterans with hyperlipidemia who had undergone bariatric surgery at 1 of 12 Veterans Affairs bariatric centers in 2000 to 2006 from the Veterans Affairs National Surgical Quality Improvement Program data. We also identified the medications that had been prescribed and discontinued using the Veterans Affairs administrative data. Medication discontinuation was estimated using a logistic regression model. Results: Of the 284 veterans with diabetes and 298 with hyperlipidemia, 52% and 40% had discontinued their medications at 1 year, respectively. The veterans with diabetes were more likely to discontinue medication if they had been taking oral hypoglycemic agents alone (odds ratio 2.77, P < .001) than were those taking insulin or oral hypoglycemic agents and insulin. The veterans with hyperlipidemia were more likely to discontinue medication if they had only been taking fibrates (odds ratio 6.15, P < .01) than were those veterans taking statins and fibrates. Conclusion: Bariatric surgery led to significant medication discontinuation within 1 year for high-risk veterans with diabetes or hyperlipidemia. (Surg Obes Relat Dis 2010;6:601-607.) Published by Elsevier Inc. C1 [Maciejewski, Matthew L.; Kavee, Andrew L.] Durham Vet Affairs Med Ctr, Ctr Hlth Serv Res Primary Care, Durham, NC 27705 USA. [Maciejewski, Matthew L.] Duke Univ, Dept Med, Div Gen Internal Med, Durham, NC USA. [Livingston, Edward H.] Univ Texas SW Med Ctr Dallas, Div Gastrointestinal & Endocrine Surg, Dallas, TX 75390 USA. [Livingston, Edward H.] Vet Affairs N Texas Hlth Care Syst, Dallas, TX USA. [Livingston, Edward H.] Univ Texas Arlington, Arlington, TX 76019 USA. [Kahwati, Leila C.] Natl Ctr Hlth Promot & Dis Prevent, Off Patient Care Serv, Vet Hlth Adm, Dept Vet Affairs, Durham, NC USA. [Henderson, William G.] Denver Vet Affairs Med Ctr, Denver, CO USA. [Henderson, William G.] Univ Colorado, Dept Biostat, Sch Publ Hlth, Aurora, CO USA. [Henderson, William G.] Univ Colorado, Colorado Hlth Outcomes Program, Aurora, CO USA. [Arterburn, David E.] Grp Hlth Res Inst, Seattle, WA USA. [Arterburn, David E.] Univ Washington, Dept Med, Div Gen Internal Med, Seattle, WA USA. RP Maciejewski, ML (reprint author), Durham Vet Affairs Med Ctr, Ctr Hlth Serv Res Primary Care, 508 Fulton St,Mail Stop 152, Durham, NC 27705 USA. EM matthew.maciejewski@va.gov FU Office of Research and Development, Health Services Research and Development Service, Department of Veterans Affairs [IIR 05-201]; Takeda Pharmaceuticals; Surgical Review Corporation FX Supported by the Office of Research and Development, Health Services Research and Development Service, Department of Veterans Affairs (IIR 05-201) and has been reviewed and approved by the Surgical Quality Data Use Group (SQDUG), Office of Patient Care Services.; Dr. Maciejewski has received consultation funds from Takeda Pharmaceuticals and the Surgical Review Corporation, and owns stock in Amgen. NR 25 TC 12 Z9 12 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1550-7289 J9 SURG OBES RELAT DIS JI Surg. Obes. Relat. Dis. PD NOV-DEC PY 2010 VL 6 IS 6 BP 601 EP 607 DI 10.1016/j.soard.2010.07.005 PG 7 WC Surgery SC Surgery GA 694UG UT WOS:000285323900003 PM 20965791 ER PT J AU West-Smith, L Sogg, S AF West-Smith, Lisa Sogg, Stephanie TI Creating a credential for bariatric behavioral health professionals: potential benefits, pitfalls, and provider opinion SO SURGERY FOR OBESITY AND RELATED DISEASES LA English DT Article DE Adult; Mental health services; Patient selection; Bariatric Surgery; Methods; Psychology; Standards; Obesity; Morbid obesity; Diagnosis; Surgery; Practice guidelines; Preoperative care/methods; Treatment outcome ID WEIGHT-LOSS SURGERY; BOSTON INTERVIEW; PSYCHOSOCIAL EVALUATION; OBESITY SURGERY; GASTRIC BYPASS; MENTAL-HEALTH; CANDIDATES; PATIENT; GUIDELINES; PREDICTORS AB Background: Since the 1991 recommendation by the National Institutes of Health-sponsored consensus development conference, preoperative psychosocial evaluation of weight loss surgery patients has been adopted by >80% of weight loss surgery programs. Although some published suggestions for conducting evaluations exist, no formal guidelines have been published specifying the qualifications, content knowledge, or clinical experience for the behavioral health professionals who conduct them. As a result, the backgrounds of behavioral health professionals working with bariatric surgery patients are varied, and no mechanism exists to ensure consistent quality of care. To obtain expert opinion on this issue, a survey of the American Society for Metabolic and Bariatric Surgery membership was conducted using an Internet-based survey. Methods: American Society for Metabolic and Bariatric Surgery members of all disciplines were invited by electronic mail to complete an Internet-based survey. Separate forms were created for behavioral health providers and for members of other disciplines. Results: A total of 409 American Society for Metabolic and Bariatric Surgery members responded (60 behavioral health and 349 nonbehavioral health). Of the 409 respondents, 95% indicated a belief that it is important for behavioral health providers to have specialty knowledge; 87% indicated a belief that specialty experience is important; and 70.6% favored the development of a specialty credential for bariatric behavioral health providers to regulate the quality of patient care. However, the respondents also reported concerns about creating such a credential. Conclusion: Our results reflect widespread opinion that the provision of bariatric behavioral health services requires specialty knowledge and experience and that a credentialing system would help regulate the standard of care in the field. However, some concerns about credential development remain. (Surg Obes Relat Dis 2010;6:695-701.) (C) 2010 American Society for Metabolic and Bariatric Surgery. All rights reserved. C1 [West-Smith, Lisa] Georgetown Community Hosp, Bariatr Ctr, Georgetown, KY 40324 USA. [Sogg, Stephanie] Massachusetts Gen Hosp, Weight Ctr, Boston, MA 02114 USA. [Sogg, Stephanie] Harvard Univ, Sch Med, Boston, MA USA. RP West-Smith, L (reprint author), Georgetown Community Hosp, Bariatr Ctr, 1140 Lexington Rd, Georgetown, KY 40324 USA. EM Lisa.West-Smith@lpnt.net RI lyp, maggie/G-1471-2011 NR 25 TC 4 Z9 4 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1550-7289 J9 SURG OBES RELAT DIS JI Surg. Obes. Relat. Dis. PD NOV-DEC PY 2010 VL 6 IS 6 BP 695 EP 701 DI 10.1016/j.soard.2010.03.289 PG 7 WC Surgery SC Surgery GA 694UG UT WOS:000285323900019 PM 20688579 ER PT J AU Eisner, BH Zargooshi, J Berger, AD Cooperberg, MR Doyle, SM Sheth, S Stoller, ML AF Eisner, Brian H. Zargooshi, Javaad Berger, Aaron D. Cooperberg, Matthew R. Doyle, Sean M. Sheth, Sonali Stoller, Marshall L. TI Gender differences in subcutaneous and perirenal fat distribution SO SURGICAL AND RADIOLOGIC ANATOMY LA English DT Article DE Fat; Distribution; Nephrectomy; Perirenal; Subcutaneous ID BODY-MASS INDEX; SEX-DIFFERENCES AB Purpose Body mass index (BMI) has been shown to influence the outcome of various surgical procedures. The purpose of this study is to assess the relationship between BMI, gender, and the distribution of subcutaneous and perirenal fat. Methods A retrospective review was performed for 123 patients who underwent radical or partial nephrectomy. Preoperative CT scans were reviewed by two independent observers. Subcutaneous fat was measured at three locations and perirenal fat was measured at six locations. Statistical analysis was performed using the Student's t test and the Pearson's correlation coefficient. Results Mean anterior subcutaneous fat was significantly greater in females than in males (2.54 vs. 1.78 cm, p < 0.001) as was mean right posterolateral subcutaneous fat (2.78 vs. 2.21 cm, p = 0.03). With regard to perirenal fat, men were greater than women for all perirenal locations around the left kidney. For the right kidney, men were greater than women for four out of six perirenal positions. In both men and women, BMI was strongly correlated with subcutaneous fat. However, BMI was weakly correlated with perirenal fat. Conclusions Women exceed men in subcutaneous fat, while men exceed women in perirenal fat. Obese patients are very likely to have large amounts of subcutaneous fat, but will not necessarily have proportionally increased fat around their kidneys when compared to the patients with lower BMI. These differences may have important implications for surgical approaches to the kidney. C1 [Eisner, Brian H.] Massachusetts Gen Hosp, Dept Urol, Boston, MA 02114 USA. [Zargooshi, Javaad; Berger, Aaron D.; Cooperberg, Matthew R.; Doyle, Sean M.; Sheth, Sonali; Stoller, Marshall L.] Univ Calif San Francisco, Dept Urol, San Francisco, CA 94143 USA. RP Eisner, BH (reprint author), Massachusetts Gen Hosp, Dept Urol, GRB 1102,55 Fruit St, Boston, MA 02114 USA. EM beisner@partners.org NR 9 TC 10 Z9 10 U1 1 U2 4 PU SPRINGER FRANCE PI PARIS PA 22 RUE DE PALESTRO, PARIS, 75002, FRANCE SN 1279-8517 J9 SURG RADIOL ANAT JI Surg. Radiol. Anat. PD NOV PY 2010 VL 32 IS 9 BP 879 EP 882 DI 10.1007/s00276-010-0692-7 PG 4 WC Anatomy & Morphology; Radiology, Nuclear Medicine & Medical Imaging; Surgery SC Anatomy & Morphology; Radiology, Nuclear Medicine & Medical Imaging; Surgery GA 688NK UT WOS:000284856500010 PM 20607260 ER PT J AU Davis, AE Lu, FX Mejia, P AF Davis, Alvin E., III Lu, Fengxin Mejia, Pedro TI C1 inhibitor, a multi-functional serine protease inhibitor SO THROMBOSIS AND HAEMOSTASIS LA English DT Article DE C1 inhibitor; complement; kallikrein kinin system; sepsis; ischaemia reperfusion injury ID HEREDITARY ANGIONEUROTIC-EDEMA; MOLECULAR-WEIGHT KININOGEN; ISCHEMIA-REPERFUSION INJURY; ESCHERICHIA-COLI O157-H7; N-LINKED GLYCOSYLATION; PURIFIED 1ST COMPONENT; C1-ESTERASE INHIBITOR; VASCULAR-PERMEABILITY; ESTERASE INHIBITOR; HUMAN COMPLEMENT AB C1 inhibitor (C1INH) is a serpin that regulates both complement and contact (kallikrein kinin) system activation It consists of a serpin do main that is highly homologous to other serpins and an amino terminal non serpin mum like domain Deficiency of C1INH results in hereditary angioedema a disease characterised by episodes of angioedema of the skin or the mucosa of the gastrointestinal tract or the oropharynx AI though early data suggested that angioedema was mediated via corn plement system activation the preponderance of the data indicate that bradykinin is the mediator In the past few years, it has become apparent that C1INH has additional anti inflammatory functions independent of protease inhibition These include interactions with leukocytes that may result in enhanced phagocytosis with endothelial cells via E and P selectins that interfere with leukocyte rolling and in turn results in suppression of transmigration of leukocytes across the endothelium and interactions with extracellular matrix components that may serve to concentrate C1INH at sites of inflammation In addition C1INH sup presses gram negative sepsis and endotoxin shock, partly via direct interaction with endotoxin that interferes with its interaction with macro phages thereby suppressing tumour necrosis factor a and other in flammatory mediators C1INH treatment improves outcome in a number of disease models including sepsis and other bacterial infections possibly malaria, ischaemia reperfusion injury (intestinal, he patic muscle cardiac, brain), hyper acute transplant rejection and other inflammatory disease models Recent data suggest that this effectiveness is the result of mechanisms that do not require protease inhibition in addition to both complement and contact system activation C1 [Davis, Alvin E., III; Lu, Fengxin; Mejia, Pedro] Harvard Univ, Sch Med, Immune Dis Inst, Childrens Hosp Boston,Program Cellular & Mol Med, Boston, MA 02115 USA. RP Davis, AE (reprint author), Harvard Univ, Sch Med, Immune Dis Inst, Childrens Hosp Boston,Program Cellular & Mol Med, 3 Blackfan Circle,3rd Floor, Boston, MA 02115 USA. FU National Institutes of Health [RO1-AI057366, R37-HD22082] FX The studies described from the author's laboratory were supported by National Institutes of Health Grants RO1-AI057366 and R37-HD22082 NR 87 TC 78 Z9 81 U1 0 U2 16 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD NOV PY 2010 VL 104 IS 5 SI SI BP 886 EP 893 DI 10.1160/TH10.01.0073 PG 8 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 684BS UT WOS:000284522600004 PM 20806108 ER PT J AU Wolpin, BM Kabrhel, C Varraso, R Kraft, P Rimm, EB Goldhaber, SZ Camargo, CA Fuchs, CS AF Wolpin, Brian M. Kabrhel, Christopher Varraso, Raphaelle Kraft, Peter Rimm, Eric B. Goldhaber, Samuel Z. Camargo, Carlos A., Jr. Fuchs, Charles S. TI Prospective study of ABO blood type and the risk of pulmonary embolism in two large cohort studies SO THROMBOSIS AND HAEMOSTASIS LA English DT Article DE Pulmonary embolism; inherited coagulation disorders; epidemiological studies ID VON-WILLEBRAND-FACTOR; INTERCELLULAR-ADHESION MOLECULE-1; VENOUS THROMBOEMBOLIC DISEASE; DEEP-VEIN THROMBOSIS; FACTOR-V-LEIDEN; PANCREATIC-CANCER; GENETIC-VARIATION; ETIOLOGY LITE; INFLAMMATION; VARIANTS AB Prior studies have suggested an association of ABO blood type and the risk of venous thromboembolism however, most studies were retrospective and lacked important covariates or validated endpoints More over risk estimates varied widely across studies Therefore we prospectively examined the association of blood type and the risk of incident pulmonary embolism (PE) in two large cohort studies, the Nurses' Health Study and Health Professionals Follow up Study During 1,010 378 person years of follow up among 77,025 women and 30 105 men 499 participants developed PE Compared to those with 0 blood type participants with non 0 blood type had multivariable adjusted hazard ratios (HR) of 1 86 (95% CI, 1 35-2 57) for idiopathic PE, 1129 (95% CI, 1 03-1 62) for non idiopathic PE and 1 46 (95% CI 1 22-1 76) for any PE Hazard ratios were similar for participants with blood types A, B, and AB Age adjusted absolute rates of idiopathic PE over 10 years of follow up differed by blood type 0 11% for 0, 0 20 701 for A 0 19% for AB, and 0 21% for B For idiopathic PE, the population attributable fraction was 33% for inheritance of non 0 blood type Among past and current smokers, participants with non 0 vs 0 blood type had a HR for idiopathic PE of 256 (95% CI, 1 61-4 08) Among never smokers the HR for idiopathic PE was 1 30 (95% CI 0 82-2 05 P(interaction)=0 04) In two large, prospective cohorts ABO blood type was significantly associated with the risk of idiopathic and non idiopathic PE, with even greater risk for idiopathic PE among current and past smokers with non O blood type C1 [Wolpin, Brian M.; Fuchs, Charles S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Goldhaber, Samuel Z.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Cardiovasc Div, Boston, MA 02115 USA. [Kabrhel, Christopher; Camargo, Carlos A., Jr.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. [Varraso, Raphaelle] INSERM, Epidemiol & Biostat U780, Villejuif, France. [Varraso, Raphaelle] Univ Paris Sud, Villejuif, France. [Kraft, Peter; Rimm, Eric B.; Camargo, Carlos A., Jr.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Rimm, Eric B.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. [Rimm, Eric B.; Camargo, Carlos A., Jr.; Fuchs, Charles S.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. [Rimm, Eric B.; Camargo, Carlos A., Jr.; Fuchs, Charles S.] Harvard Univ, Sch Med, Boston, MA USA. RP Wolpin, BM (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. RI Varraso, Raphaelle/R-8740-2016 OI Varraso, Raphaelle/0000-0002-3338-7825 FU National Cancer Institute; National Institutes of Health [P01 CA87969, P01 CA55075, P50 CA127003, R01 CA124908, K07 CA140790, R21 AG31079]; American Society FX This work was supported by the National Cancer Institute National Institutes of Health [Grants No P01 CA87969 P01 CA55075 P50 CA127003 R01 CA124908 K07 CA140790 R21 AG31079] and support from an American Society of Clinical Oncology Career Development Award (BMW) NR 47 TC 15 Z9 15 U1 0 U2 1 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD NOV PY 2010 VL 104 IS 5 SI SI BP 962 EP 971 DI 10.1160/TH10.05.0312 PG 10 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 684BS UT WOS:000284522600014 PM 20886188 ER PT J AU Becker, AE Fay, K Agnew-Blais, J Guarnaccia, PM Striegel-Moore, RH Gilman, SE AF Becker, Anne E. Fay, Kristen Agnew-Blais, Jessica Guarnaccia, Peter M. Striegel-Moore, Ruth H. Gilman, Stephen E. TI Development of a Measure of "Acculturation" for Ethnic Fijians: Methodologic and Conceptual Considerations for Application to Eating Disorders Research SO TRANSCULTURAL PSYCHIATRY LA English DT Article DE acculturation; assessment; eating disorders; Fiji; global; western ID FEMALE COLLEGE-STUDENTS; CULTURE-BOUND SYNDROMES; BODY-IMAGE; ANOREXIA-NERVOSA; MENTAL-HEALTH; ADOLESCENT GIRLS; COMMUNITY SAMPLE; AMERICAN WOMEN; SELF-IDENTITY; SCALE AB Acculturation has been examined as a risk factor for eating disorders, but interpretation of findings has been limited by inconsistent operationalization of this construct across studies. The study aim was to develop and evaluate a population-specific measure of acculturation for ethnic Fijian adolescent schoolgirls, to use in future analyses related to eating disorders. Our findings suggest that acculturation is a multidimensional construct characterized by distinct, though related, dimensions of orientation to ethnic Fijian and/or western/global culture with respect to a range of behaviors and attitudes. In contrast to theoretical models positing uni-dimensional, orthogonal, or oblique relations between cultural identities in individuals undergoing acculturation, our study findings support a heterogeneous pattern among correlations of dimensions across contrasting cultural identities. We suggest multidimensional measures of acculturation are optimal - and socio-demographic proxies inadequate - for characterization of this complex process for health research. C1 [Becker, Anne E.] Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA 02115 USA. [Becker, Anne E.] Massachusetts Gen Hosp, Eating Disorders Clin & Res Program, Boston, MA 02114 USA. [Fay, Kristen] Tufts Univ, Inst Appl Res Youth Dev, Medford, MA 02155 USA. [Agnew-Blais, Jessica; Gilman, Stephen E.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Guarnaccia, Peter M.] Rutgers State Univ, Dept Human Ecol, New Brunswick, NJ 08901 USA. [Striegel-Moore, Ruth H.] Wesleyan Univ, Dept Psychol, Middletown, CT 06459 USA. [Gilman, Stephen E.] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. RP Becker, AE (reprint author), Harvard Univ, Sch Med, Dept Global Hlth & Social Med, Boston, MA 02115 USA. EM anne_becker@hms.harvard.edu RI Agnew-Blais, Jessica/L-9236-2015; Gilman, Stephen/E-7632-2010 OI Agnew-Blais, Jessica/0000-0002-0755-6867; Gilman, Stephen/0000-0002-8331-6419 FU NIMH NIH HHS [K23 MH068575] NR 108 TC 1 Z9 1 U1 3 U2 11 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1363-4615 J9 TRANSCULT PSYCHIATRY JI Transcult. Psychiatry PD NOV PY 2010 VL 47 IS 5 BP 754 EP 788 DI 10.1177/1363461510382153 PG 35 WC Anthropology; Psychiatry SC Anthropology; Psychiatry GA 681ZC UT WOS:000284362300005 PM 21088103 ER PT J AU Ellis, BH Lincoln, AK Charney, ME Ford-Paz, R Benson, M Strunin, L AF Ellis, B. Heidi Lincoln, Alisa K. Charney, Meredith E. Ford-Paz, Rebecca Benson, Molly Strunin, Lee TI Mental Health Service Utilization of Somali Adolescents: Religion, Community, and School as Gateways to Healing SO TRANSCULTURAL PSYCHIATRY LA English DT Article DE Gateway Provider Model; mental health; refugee; service utilization; Somali ID IMMIGRANT CHILDREN; REFUGEE CHILDREN; TRAUMA; DISORDER; STRESS; ACCESS; CARE; PSYCHOPATHOLOGY; RESPONSES; WAR AB This mixed-method study examines the utility of the Gateway Provider Model (GPM) in understanding service utilization and pathways to help for Somali refugee adolescents. Somali adolescents living in the Northeastern United States, and their caregivers, were interviewed. Results revealed low rates of use of mental health services. However other sources of help, such as religious and school personnel, were accessed more frequently. The GPM provides a helpful model for understanding refugee youth access to services, and an elaborated model is presented showing how existing pathways to help could be built upon to improve refugee youth access to services. C1 [Ellis, B. Heidi; Benson, Molly] Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Psychiat, Boston, MA 02115 USA. [Lincoln, Alisa K.] Northeastern Univ, Boston, MA USA. [Charney, Meredith E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Ford-Paz, Rebecca] Childrens Mem Hosp, Mood & Anxiety Program, Outpatient Psychiat Serv, Chicago, IL 60614 USA. [Strunin, Lee] Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. RP Ellis, BH (reprint author), Harvard Univ, Sch Med, Childrens Hosp Boston, Dept Psychiat, 21 Autumn St, Boston, MA 02115 USA. EM heidi.ellis@childrens.harvard.edu FU NIMH NIH HHS [R21 MH070261, R21 MH70261] NR 41 TC 23 Z9 23 U1 7 U2 21 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1363-4615 J9 TRANSCULT PSYCHIATRY JI Transcult. Psychiatry PD NOV PY 2010 VL 47 IS 5 BP 789 EP 811 DI 10.1177/1363461510379933 PG 23 WC Anthropology; Psychiatry SC Anthropology; Psychiatry GA 681ZC UT WOS:000284362300006 PM 21088104 ER PT J AU Casas-Aparicio, G Castillo-Martinez, L Orea-Tejeda, A Abasta-Jimenez, M Keirns-Davies, C Rebollar-Gonzalez, V AF Casas-Aparicio, G. Castillo-Martinez, L. Orea-Tejeda, A. Abasta-Jimenez, M. Keirns-Davies, C. Rebollar-Gonzalez, V. TI The Effect of Successful Kidney Transplantation on Ventricular Dysfunction and Pulmonary Hypertension SO TRANSPLANTATION PROCEEDINGS LA English DT Article ID CONGESTIVE-HEART-FAILURE; STAGE RENAL-DISEASE; UREMIC CARDIOMYOPATHY; SYSTOLIC DYSFUNCTION; DIALYSIS PATIENTS; RISK-FACTORS; HEMODIALYSIS; IMPROVEMENT; PREVALENCE AB Background. Heart disease is a frequent complication of chronic kidney disease and the major cause of death in patients on renal replacement therapy. The purpose of this study was to evaluate the impact of successful kidney transplantation on systolic and diastolic ventricular dysfunction and pulmonary arterial hypertension in patients with chronic kidney disease (CKD). Methods. The study included 35 patients >18 years of age with CKD who had successful kidney transplantations. Ventricular function and pulmonary arterial pressure were evaluated by echocardiography before and 1 year after transplant. Results. The mean age of subjects was 40 +/- 14 years, and 63% were men. Mean left ventricular ejection fraction (LVEF) was 52 +/- 16%. Before transplant, 28 (80%) of the patients had ventricular dysfunction (34.3% diastolic and 45.7% systolic). Pulmonary arterial hypertension was found in 48.6%. Ventricular dysfunction was associated with dialysis of >2 years duration before transplant. The LVEF of the entire group increased from 52% to 64% (P < .001) by 12 months after kidney transplant. Left ventricular diameters, wall thickness, and pulmonary arterial systolic pressure decreased significantly after transplantation Echocardiograms became normal 1 year after transplant in 8 (66.7%) of the patients with diastolic dysfunction and 9 (56.2%) with systolic dysfunction, and diastolic dysfunction persisted in 5 (31.2%). Conclusions. Because kidney transplantation led to considerable improvement in left ventricular systolic and diastolic function as well as pulmonary arterial pressure of patients with CKD, optimal treatment for dysfunction and transplant as soon as possible is recommended. C1 [Castillo-Martinez, L.; Orea-Tejeda, A.] Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Heart Failure Clin, Mexico City 03100, DF, Mexico. [Castillo-Martinez, L.; Orea-Tejeda, A.; Rebollar-Gonzalez, V.] Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Cardiol, Mexico City 03100, DF, Mexico. [Casas-Aparicio, G.; Abasta-Jimenez, M.] Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Dept Nephrol, Mexico City 03100, DF, Mexico. [Keirns-Davies, C.] Massachusets Gen Hosp, Boston, MA USA. RP Orea-Tejeda, A (reprint author), Inst Nacl Ciencias Med & Nutr Salvador Zubiran, Heart Failure Clin, Providencia 1218-A 402 Col Valle, Mexico City 03100, DF, Mexico. EM artorea@yahoo.com.mx RI Castillo-Martinez, Lilia/H-3750-2013 NR 20 TC 15 Z9 17 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0041-1345 J9 TRANSPL P JI Transplant. Proc. PD NOV PY 2010 VL 42 IS 9 BP 3524 EP 3528 DI 10.1016/j.transproceed.2010.06.026 PG 5 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 689ZO UT WOS:000284969800032 PM 21094809 ER PT J AU Jeon, CY Harries, AD Baker, MA Hart, JE Kapur, A Lonnroth, K Ottmani, SE Goonesekera, S Murray, MB AF Jeon, Christie Y. Harries, Anthony D. Baker, Meghan A. Hart, Jessica E. Kapur, Anil Loennroth, Knut Ottmani, Salah-Eddine Goonesekera, Sunali Murray, Megan B. TI Bi-directional screening for tuberculosis and diabetes: a systematic review SO TROPICAL MEDICINE & INTERNATIONAL HEALTH LA English DT Review DE tuberculosis; diabetes; screening ID PULMONARY TUBERCULOSIS; RISK-FACTORS; ACTIVE TUBERCULOSIS; GLUCOSE-INTOLERANCE; NATIONAL-SURVEY; MELLITUS; PREVALENCE; EPIDEMICS; CONVERGENCE; INFECTION AB OBJECTIVE To assess the yield of finding additional TB or diabetes mellitus (DM) cases through systematic screening and to determine the effectiveness of preventive TB therapy in people with DM. METHODS We systematically reviewed studies that had screened for active TB or implemented preventive therapy for TB among people with DM, and those that screened for DM among patients with TB. We searched published literature through PubMed and EMBASE and included studies that reported the number of TB cases identified among people with DM; the number of DM cases identified among patients with TB, or the relative incidence of TB between people with DM who received a TB prophylaxis and those who did not. We assessed the yield of screening by estimating the prevalence of TB or DM in each study, the prevalence ratio and difference where comparison populations were available, and the number of persons to screen to detect an additional case of TB or DM. RESULTS Twelve studies on screening for TB in people with DM and 18 studies on screening for DM in patients with TB met our inclusion criteria. Screening for TB in persons with DM demonstrated that TB prevalence in this population is high, ranging from 1.7% to 36%, and increasing with rising TB prevalence in the underlying population as well as with DM severity. Screening patients with TB for DM also yielded high prevalences of DM ranging from 1.9% to 35%. Two studies examining the role of TB preventive therapy in people with DM did not provide sufficient details for clear evidence of the effectiveness. CONCLUSION Active screening leads to the detection of more TB and DM with varying yield. This review highlights the need for further research in screening and preventive therapy. C1 [Jeon, Christie Y.; Baker, Meghan A.; Goonesekera, Sunali; Murray, Megan B.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Harries, Anthony D.] Int Union TB & Lung Dis, Paris, France. [Harries, Anthony D.] London Sch Hyg & Trop Med, London WC1, England. [Baker, Meghan A.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Hart, Jessica E.] Brown Univ, Warren Alpert Med Sch, Providence, RI 02912 USA. [Kapur, Anil] World Diabet Fdn, Lyngby, Denmark. [Loennroth, Knut; Ottmani, Salah-Eddine] WHO, Stop TB Dept, CH-1211 Geneva, Switzerland. [Murray, Megan B.] Brigham & Womens Hosp, Div Global Hlth Equ, Boston, MA 02115 USA. RP Murray, MB (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, 641 Huntington Ave, Boston, MA 02115 USA. EM megan.murray.epi@gmail.com RI Lonnroth, Knut/L-2339-2014 OI Lonnroth, Knut/0000-0001-5054-8240 FU World Diabetes Foundation FX This review was commissioned by the International Union Against Tuberculosis and Lung Disease, the World Health Organization and the World Diabetes Foundation, and funded by the World Diabetes Foundation. NR 52 TC 66 Z9 67 U1 0 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1360-2276 J9 TROP MED INT HEALTH JI Trop. Med. Int. Health PD NOV PY 2010 VL 15 IS 11 BP 1300 EP 1314 DI 10.1111/j.1365-3156.2010.02632.x PG 15 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 667CA UT WOS:000283169000006 PM 20958887 ER PT J AU Martins, FC Botelho, MF Cabrita, AM de Oliveira, CF AF Martins, Filipe Correia Botelho, Maria Filomena Cabrita, Antonio Manuel de Oliveira, Carlos Freire TI Influence of normal mammary epithelium on breast cancer progression: the protective role of early pregnancy SO TUMORI LA English DT Article DE breast cancer; pregnancy; mammary epithelium ID HORMONE-INDUCED PROTECTION; STEM-CELLS; CARCINOGENESIS; CHEMOPREVENTION; ENVIRONMENT; EXPRESSION AB Aims and background. The microenvironment has a well recognized role in breast cancer progression. Despite different theories, the mechanism of early pregnancy protection in mammary carcinogenesis is unknown. Since pregnancy is responsible for mammary gland differentiation, we tested the hypothesis that differentiated mammary epithelial cells may inhibit breast cancer progression. In other words, the protective role of early pregnancy could be due to the inhibitory influences of the more differentiated mammary tissue. Methods. In order to test our hypothesis, we used 30 female Balb/c nude mice and MCF-7 cells of breast adenocarcinoma. The female mice were divided into two test groups, group I (GI) and group II (GII), and a control group. In GII, the animals were submitted to epithelial removal in the left fourth inguinal mammary gland at 3 weeks of age. Both groups were given continuous hormonal treatment to simulate the pregnancy development of the mammary gland. Two million MCF-7 cells were then injected into the fourth inguinal mammary gland (GI) or in the respective cleared mammary fat pad (GII). Five weeks later the mice were sacrificed and their tumors removed. Tumor development rates and tumor volumes were determined and proliferation and apoptosis were evaluated by immunohistochemistry. Results. Tumors of GII mice had a larger mean volume than those of GI mice (P = 0.001, Mann-Whitney U-test) and an apparent increase in proliferation, demonstrated by a higher staining intensity for proliferating cell nuclear antigen (PCNA). As tumors presented caspase 8 staining, there may be apoptotic activation involved in cell death, mainly through an extrinsic pathway. Conclusions. These results suggest that a differentiated intact mammary gland may have an inhibitory influence on mammary tumor growth in mice. Free full text available at www.tumorionline.it C1 [Martins, Filipe Correia; de Oliveira, Carlos Freire] Univ Hosp Coimbra, Dept Gynecol, Coimbra, Portugal. [Martins, Filipe Correia; Botelho, Maria Filomena; Cabrita, Antonio Manuel; de Oliveira, Carlos Freire] Coimbra Med Sch, CIMAGO Oncobiol Genet & Environm Res Ctr, Coimbra, Portugal. [Martins, Filipe Correia; Botelho, Maria Filomena] Coimbra Med Sch, IBILI, Biophys & Biomath Inst, Coimbra, Portugal. [Martins, Filipe Correia; Cabrita, Antonio Manuel] Coimbra Med Sch, Inst Expt Pathol, Coimbra, Portugal. RP Martins, FC (reprint author), Dana Farber Canc Inst, D740,44 Binney St, Boston, MA 02115 USA. EM filipe_martins@dfci.harvard.edu RI Botelho, Maria Filomena/G-1860-2011; OI Botelho, Maria Filomena/0000-0001-7202-1650; Cabrita, Antonio/0000-0001-5165-5849 NR 24 TC 2 Z9 2 U1 0 U2 4 PU PENSIERO SCIENTIFICO EDITOR PI ROME PA VIA BRADANO 3/C, 00199 ROME, ITALY SN 0300-8916 J9 TUMORI JI Tumori PD NOV-DEC PY 2010 VL 96 IS 6 BP 999 EP 1003 PG 5 WC Oncology SC Oncology GA 737OR UT WOS:000288578600018 PM 21388065 ER PT J AU Gethin-Jones, TL Noble, VE Morse, CR AF Gethin-Jones, Thomas L. Noble, Vicki E. Morse, Christopher R. TI QUANTIFICATION OF DIAPHRAGM FUNCTION USING ULTRASOUND: EVALUATION OF A NOVEL TECHNIQUE SO ULTRASOUND IN MEDICINE AND BIOLOGY LA English DT Article DE Ultrasound; Diaphragm function; Thoracic surgery ID DYSFUNCTION; MOTION AB A novel method of image analysis for quantifying diaphragmatic motion is described using ultrasound. Nineteen patients scheduled for thoracic surgery were evaluated with ultrasound preoperatively and through their postoperative hospital stay. Diaphragmatic motion was measured using a horizontal on-screen ruler, allowing for quantification and tracking of dynamic diaphragm function. A percentage (73.5%) of all attempted measurements was quantifiable. Preoperative measurements of left and right diaphragm movement were correlated and there was no significant difference between the two. Postoperative diaphragm movement ipsilateral to the incision was statistically significantly less when compared to the contralateral side (p = 0.02 vs. p = 0.19). While not universally feasible in all patients, this method for quantifying diaphragmatic function is the only known imaging technique that can be performed at the bedside. Further evaluation of the impact of diaphragmatic dysfunction on patients undergoing thoracic surgery and its correlation with dyspnea is planned. (E-mail: tgethin-jones@partners.org) (C) 2010 World Federation for Ultrasound in Medicine & Biology. C1 [Gethin-Jones, Thomas L.; Morse, Christopher R.] Massachusetts Gen Hosp, Div Thorac Surg, Boston, MA 02114 USA. [Noble, Vicki E.] Dept Emergency Med, Boston, MA USA. RP Gethin-Jones, TL (reprint author), Massachusetts Gen Hosp, Div Thorac Surg, Blake 1570,55 Fruit St, Boston, MA 02114 USA. EM tgethin-jones@partners.org NR 8 TC 6 Z9 6 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-5629 J9 ULTRASOUND MED BIOL JI Ultrasound Med. Biol. PD NOV PY 2010 VL 36 IS 11 BP 1965 EP 1969 DI 10.1016/j.ultrasmedbio.2010.08.003 PG 5 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 668KJ UT WOS:000283267200021 PM 20870347 ER PT J AU Williams, SB Chen, MH D'Amico, AV Weinberg, AC Kacker, R Hirsch, MS Richie, JP Hu, JC AF Williams, Stephen B. Chen, Ming-Hui D'Amico, Anthony V. Weinberg, Aaron C. Kacker, Ravi Hirsch, Michelle S. Richie, Jerome P. Hu, Jim C. TI Radical Retropubic Prostatectomy and Robotic-assisted Laparoscopic Prostatectomy: Likelihood of Positive Surgical Margin(s) SO UROLOGY LA English DT Article ID CANCER; EXPERIENCE; OUTCOMES; SPECIMENS; LOCATION; SURGEONS; VOLUME AB OBJECTIVES To evaluate whether the surgical approach influenced the likelihood of a positive surgical margin (PSM) adjusting for known preoperative predictors of PSM, year of radical prostatectomy, body mass index, use of nerve sparing, and patient age at radical prostatectomy. METHODS The study cohort comprised 950 consecutively treated men with clinically localized prostate cancer who underwent open radical retropubic (RRP, n = 346) or robotic-assisted (RALP, N = 604) prostatectomy by a single surgeon (J.P.R., J.C.H.) at the Brigham and Women's Hospital from 2005 to 2008 and had complete information on baseline patient and tumor characteristics. Univariate and multivariate logistic regression analyses were performed to identify clinical factors significantly associated with the likelihood of a PSM. RESULTS Men undergoing RALP compared with RRP were more likely to have a PSM (adjusted odds ratio 1.9; 95% confidence interval: 1.2-3.1, P = .0095). Significant interaction (P = .0085) was noted between the type of surgical approach and whether nerve sparing was performed on the likelihood of a PSM. Specifically, a significantly lower PSM rate was observed for men undergoing nerve sparing and RRP compared with nerve sparing and RALP (7.6% vs 13.5%, P = .007), whereas opposite trend was noted (P = .09) for men undergoing a non-nerve-sparing approach. CONCLUSIONS Men undergoing RALP compared with RRP seem to have a greater likelihood of a PSM. Further study is needed to delineate whether this increase is due to an intrinsic limitation of RALP or unknown confounders. UROLOGY 76: 1097-1101, 2010. (C) 2010 Elsevier Inc. C1 [Williams, Stephen B.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Urol,ASBII, Boston, MA 02115 USA. Univ Connecticut, Dept Stat, Storrs, CT 06269 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiat Oncol, Boston, MA 02115 USA. Harvard Univ, Dana Farber Canc Inst, Sch Med, Boston, MA 02115 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Williams, SB (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Urol,ASBII, 75 Francis St, Boston, MA 02115 USA. EM swilliams22@partners.org OI weinberg, aaron/0000-0002-0957-5703 NR 31 TC 43 Z9 44 U1 2 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI Urology PD NOV PY 2010 VL 76 IS 5 BP 1097 EP 1101 DI 10.1016/j.urology.2009.11.079 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 675QD UT WOS:000283844600019 PM 20303147 ER PT J AU Beer, TM Benavides, M Emmons, SL Hayes, M Liu, GH Garzotto, M Donovan, D Katovic, N Reeder, C Eilers, K AF Beer, Tomasz M. Benavides, Maria Emmons, Sandra L. Hayes, Margaret Liu, Guohui Garzotto, Mark Donovan, Deirdre Katovic, Nina Reeder, Caron Eilers, Kristine TI Acupuncture for Hot Flashes in Patients With Prostate Cancer SO UROLOGY LA English DT Article ID GENE-RELATED PEPTIDE; RANDOMIZED CONTROLLED-TRIAL; QUALITY-OF-LIFE; BREAST-CANCER; VASOMOTOR SYMPTOMS; POSTMENOPAUSAL WOMEN; LUTEINIZING-HORMONE; MEGESTROL-ACETATE; PILOT EVALUATION; BLOOD-FLOW AB OBJECTIVES To determine the effect of acupuncture on hot flash frequency and intensity, quality of life, and sleep quality in patients undergoing hormonal therapy for prostate cancer. Hot flashes are a common adverse effect of hormonal therapy for prostate cancer. METHODS Men who had a hot flash score > 4 who were receiving androgen deprivation therapy for prostate cancer underwent acupuncture with electrostimulation biweekly for 4 weeks, then weekly for 6 weeks, using a predefined treatment plan. The primary endpoint was a 50% reduction in the hot flash score after 4 weeks of therapy, calculated from the patients' daily hot flash diaries. The hot flash-related quality of life and sleep quality and biomarkers potentially related to hot flashes, including serotonin, calcitonin gene-related peptide, and urinary 5-hydroxyindoleacetic acid, were examined. RESULTS A total of 25 men were enrolled from September 2003 to April 2007. Of these, 22 were eligible and evaluable. After 4 weeks, 9 (41%, 95% confidence interval 21%-64%) of 22 patients had had a > 50% reduction in the hot flash score. Of the 22 patients, 12 (55%, 95% confidence interval 32%-76%) met this response definition at any point during the therapy course. No patient had a significant increase in hot flash score during therapy. A reduced hot flash score was associated with improvement in the hot flash-related quality of life and sleep quality. CONCLUSIONS Multiple placebo-controlled trials have demonstrated a 25% response rate to placebo treatment for hot flashes. Of the 22 patients, 41% had responded by week 4 and 55% overall in the present pilot study, providing evidence of a potentially meaningful benefit. Additional studies of acupuncture for hot flashes in this population are warranted. UROLOGY 76: 1182-1188, 2010. (C) 2010 Elsevier Inc. C1 [Beer, Tomasz M.] Oregon Hlth & Sci Univ, Div Hematol & Med Oncol, Portland, OR 97201 USA. Oregon Hlth & Sci Univ, Div Urol, Portland, OR 97201 USA. Oregon Hlth & Sci Univ, Dept Obstet & Gynecol, Portland, OR 97201 USA. Oregon Hlth & Sci Univ, Dept Family Med, Portland, OR 97201 USA. Goodlife Acupuncture, Bend, OR USA. Oregon Coll Oriental Med, Portland, OR USA. Portland VA Med Ctr, Portland, OR USA. RP Beer, TM (reprint author), Oregon Hlth & Sci Univ, Div Hematol & Med Oncol, 3303 SW Bond Ave,CII14R, Portland, OR 97201 USA. EM beert@ohsu.edu FU Oregon Health and Science University General Clinical Research Center [M01 RR000334]; Oregon Clinical and Translational Research Institute [UL1RR024140]; National Institutes of Health, Bethesda, Maryland [R21 CA098406] FX This study was supported in part by grant M01 RR000334 from the Oregon Health and Science University General Clinical Research Center, grant UL1RR024140 from the Oregon Clinical and Translational Research Institute, and grant R21 CA098406 from the National Institutes of Health, Bethesda, Maryland. NR 41 TC 14 Z9 15 U1 0 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 EI 1527-9995 J9 UROLOGY JI Urology PD NOV PY 2010 VL 76 IS 5 BP 1182 EP 1188 DI 10.1016/j.urology.2010.03.033 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 675QD UT WOS:000283844600043 PM 20494414 ER PT J AU Ahove, DA Hoffman, KE Hu, JC Choueiri, TK D'Amico, AV Nguyen, PL AF Ahove, Deborah A. Hoffman, Karen E. Hu, Jim C. Choueiri, Toni K. D'Amico, Anthony V. Nguyen, Paul L. TI Which Patients With Undetectable PSA Levels 5 Years After Radical Prostatectomy Are Still at Risk of Recurrence?-Implications for a Risk-adapted Follow-up Strategy SO UROLOGY LA English DT Article ID RANDOMIZED CLINICAL-TRIAL; DISEASE RECURRENCE; POSTOPERATIVE NOMOGRAM; BIOCHEMICAL RECURRENCE; ADJUVANT RADIOTHERAPY; SALVAGE RADIOTHERAPY; CANCER; UPDATE AB OBJECTIVES To determine the predictors of late prostate-specific antigen (PSA) failure among men with an undetectable PSA level 5 years after radical prostatectomy (RP). METHODS A total of 505 men who had undergone RP for prostate cancer from 1985 to 2000 at Brigham and Women's Hospital and who had >= 5 years of recurrence-free survival (ie, all PSA levels < 0.2 ng/mL) constituted the study cohort. Cox multivariate regression analysis was used to determine the factors associated with PSA failure after 5 years. Kaplan-Meier analysis was used to estimate the PSA failure-free survival rate. RESULTS The median follow-up was 10.7 years after RP (interquartile range 7.8-13.3). No patient had PSA failure at year 5, but the PSA failure-free survival rate for this cohort at year 10 was 88% (95% confidence interval 84.4%-91.0%) and, at year 13, was 82% (95% confidence interval 77.0%-86.0%). On multivariable regression analysis, the factors associated with failure after year 5 were Gleason score 7 (adjusted hazard ratio [AHR] 1.88, P = .036), Gleason score 8-10 (AHR 4.81, P = .002), extracapsular extension (AHR 2.37, P = .003), and seminal vesicle invasion (AHR 1.52, P = .062). CONCLUSIONS Among men with an undetectable PSA level 5 years after RP, Gleason score 7, Gleason score 8-10, extracapsular extension, and seminal vesicle invasion were significant predictors of subsequent late PSA failure. Patients with these factors (particularly Gleason score 8-10 or seminal vesicle invasion) should have continued close monitoring of their PSA level and consideration of early salvage, as appropriate. However, patients with Gleason score 6 disease were very unlikely to develop late recurrence and might be candidates for less-intense follow-up once they have passed the 5-year mark. UROLOGY 76: 1201-1205, 2010. (C) 2010 Elsevier Inc. C1 [Nguyen, Paul L.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Urol, Boston, MA 02115 USA. Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Smith Coll, Northampton, MA 01063 USA. Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Nguyen, PL (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Francis St, Boston, MA 02115 USA. EM pnguyen@LROC.harvard.edu NR 16 TC 11 Z9 11 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0090-4295 J9 UROLOGY JI Urology PD NOV PY 2010 VL 76 IS 5 BP 1201 EP 1205 DI 10.1016/j.urology.2010.03.092 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 675QD UT WOS:000283844600050 PM 20709376 ER PT J AU Basch, E Reeve, B Cleeland, C Sloan, J Schrag, D Atkinson, TM Mendoza, T Hay, J Abernethy, A Minasian, L Kwitkowski, V Trentacosti, AM Burke, L Sit, L Bruner, D AF Basch, E. Reeve, B. Cleeland, C. Sloan, J. Schrag, D. Atkinson, T. M. Mendoza, T. Hay, J. Abernethy, A. Minasian, L. Kwitkowski, V Trentacosti, A. M. Burke, L. Sit, L. Bruner, D. TI DEVELOPMENT OF THE PATIENT-REPORTED VERSION OF THE COMMON TERMINOLOGY CRITERIA FOR ADVERSE EVENTS (PRO-CTCAE) SO VALUE IN HEALTH LA English DT Meeting Abstract C1 [Basch, E.; Atkinson, T. M.; Hay, J.; Sit, L.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Reeve, B.] NCI, Bethesda, MD 20892 USA. [Cleeland, C.; Mendoza, T.] UTMD Anderson Canc Ctr, Houston, TX USA. [Sloan, J.] Mayo Clin, Rochester, MN USA. [Schrag, D.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Abernethy, A.] Duke Univ, Durham, NC USA. [Minasian, L.] NCI, Rockville, MD USA. [Burke, L.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Bruner, D.] Univ Penn, Philadelphia, PA 19104 USA. NR 0 TC 1 Z9 1 U1 0 U2 3 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1098-3015 J9 VALUE HEALTH JI Value Health PD NOV PY 2010 VL 13 IS 7 BP A274 EP A275 PG 2 WC Economics; Health Care Sciences & Services; Health Policy & Services SC Business & Economics; Health Care Sciences & Services GA 662ON UT WOS:000282818001176 ER PT J AU Fuchs, BB O'Brien, E El Khoury, JB Mylonakis, E AF Fuchs, Beth Burgwyn O'Brien, Elizabeth El Khoury, Joseph B. Mylonakis, Eleftherios TI Methods for using Galleria mellonella as a model host to study fungal pathogenesis SO VIRULENCE LA English DT Article DE filamentation; fungal pathogenesis; infection model; Galleria mellonella; model host; virulence ID CANDIDA-ALBICANS; PATHOGENICITY; VIRULENCE; LARVAE AB The facile inoculum delivery and handling of the insect Galleria mellonella make it a desirable model for the study of fungal pathogenesis. Here we present methods to study fungal virulence, filamentation and fungal cell associates with insect hemocytes using Candida albicans and Cryptococcus neoformans to illustrate the use of this model. The two types of fungi cause distinct infections; thus, we compare and contrast the infection characteristics observed in G. mellonella. The protocols presented herein can be adapted to the study of other fungal pathogens using G. mellonella as an infection model. C1 [Fuchs, Beth Burgwyn; O'Brien, Elizabeth; El Khoury, Joseph B.; Mylonakis, Eleftherios] Massachusetts Gen Hosp, Div Infect, Boston, MA 02114 USA. [El Khoury, Joseph B.] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. [El Khoury, Joseph B.] Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. RP Fuchs, BB (reprint author), Massachusetts Gen Hosp, Div Infect, Boston, MA 02114 USA. EM hfuchs@partners.org; emylonakis@partners.org NR 10 TC 93 Z9 95 U1 0 U2 14 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 2150-5594 J9 VIRULENCE JI Virulence PD NOV-DEC PY 2010 VL 1 IS 6 BP 475 EP 482 DI 10.4161/viru.1.6.12985 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 789NI UT WOS:000292521800002 PM 21178491 ER PT J AU Takeuchi, Y Fishman, J AF Takeuchi, Yasuhiro Fishman, Jay TI Long life with or without PERV SO XENOTRANSPLANTATION LA English DT Article ID PORCINE ENDOGENOUS RETROVIRUS; ISLET XENOTRANSPLANTATION; TYPE-1; TRANSMISSION C1 [Takeuchi, Yasuhiro] UCL, Div Infect & Immun, London, England. [Fishman, Jay] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. RP Takeuchi, Y (reprint author), UCL, Div Infect & Immun, London, England. EM y.takeuchi@ucl.ac.uk FU European Sixth Framework Programme [LSHB-CT-2006-037377] FX YT's xenotransplantation research has been supported by the European Sixth Framework Programme (Life Science, Genomics and Biotechnology for Health) funded project LSHB-CT-2006-037377. NR 12 TC 5 Z9 6 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD NOV-DEC PY 2010 VL 17 IS 6 BP 429 EP 430 DI 10.1111/j.1399-3089.2010.00614.x PG 2 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 695RL UT WOS:000285390200006 PM 21158943 ER PT J AU Lee, J Ryu, H AF Lee, Junghee Ryu, Hoon TI Epigenetic modification is linked to Alzheimer's disease: is it a maker or a marker? SO BMB REPORTS LA English DT Review DE Alzheimer's disease; Chromatin remodeling; DNA methylation; Epigenetic modification ID AMYLOID PRECURSOR PROTEIN; HISTONE DEACETYLASE INHIBITORS; HUNTINGTONS-DISEASE; NEURODEGENERATIVE DISORDERS; TRANSGENIC MICE; MOUSE MODEL; DNA METHYLATION; MEMORY DEFICITS; GENE-EXPRESSION; REDUCTION AB Alzheimer's disease (AD) is the most common age-dependent neurodegenerative disorder and shows progressive memory loss and cognitive decline. Intraneuronal filaments composed of aggregated hyperphosphorylated tau protein, called neurofibrillary tangles, along with extracellular accumulations of amyloid beta protein (A beta), called senile plaques, are known to be the neuropathological hallmarks of AD. In light of recent studies, epigenetic modification has emerged as one of the pathogenic mechanisms of AD. Epigenetic changes encompass an array of molecular modifications to both DNA and chromatin, including transcription factors and cofactors. In this review, we summarize how DNA methylation and changes to DNA chromatin packaging by post-translational histone modification are involved in AD. In addition, we describe the role of SIRTs, histone deacetylases, and the effect of SIRT-modulating drugs on AD. Lastly, we discuss how amyloid precursor protein (APP) intracellular domain (AICD) regulates neuronal transcription. Our understanding of the epigenomes and transcriptomes of AD may warrant future identification of novel biological markers and beneficial therapeutic targets for AD. [BMB reports 2010; 43(10): 649-655] C1 [Lee, Junghee; Ryu, Hoon] Boston Univ Sch Med, Dept Neurol, Boston, MA 02130 USA. [Lee, Junghee; Ryu, Hoon] VA Boston Healthcare Syst, Boston, MA 02130 USA. [Ryu, Hoon] Seoul Natl Univ Coll Med, Dept Biomed Sci, WCU Neurocyt Grp, Seoul 110799, South Korea. RP Ryu, H (reprint author), Boston Univ Sch Med, Dept Neurol, Boston, MA 02130 USA. EM hoonryu@bu.edu FU Korea Science & Engineering Foundation (KOSEF) [800-20080848] FX We thank KH Seong and YJ Hwang for their assistance in the preparation of the manuscript. This work was supported by a WCU Neurocytomics Program Grant (800-20080848) (H.R.) from the Korea Science & Engineering Foundation (KOSEF). NR 51 TC 22 Z9 22 U1 3 U2 11 PU KOREAN SOCIETY BIOCHEMISTRY & MOLECULAR BIOLOGY PI SEOUL PA KOREA SCIENCE & TECHNOLOGY CENTER, # 801, 635-4 , YEOKSAM-DONG, KANGNAM-KU, SEOUL, 135-703, SOUTH KOREA SN 1976-6696 J9 BMB REP JI BMB Rep. PD OCT 31 PY 2010 VL 43 IS 10 BP 649 EP 655 DI 10.3858/BMBRep.2010.43.10.649 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 675GE UT WOS:000283814000002 PM 21034526 ER PT J AU Tian, D Sun, S Lee, JT AF Tian, Di Sun, Sha Lee, Jeannie T. TI The Long Noncoding RNA, Jpx, Is a Molecular Switch for X Chromosome Inactivation SO CELL LA English DT Article ID IMPRINTED XIST EXPRESSION; EMBRYONIC STEM-CELLS; EARLY MOUSE EMBRYOS; DOSAGE COMPENSATION; TSIX TRANSCRIPTION; ANTISENSE TRANSCRIPTION; CHROMATIN-STRUCTURE; GENE; METHYLATION; REPEAT AB Once protein-coding, the X-inactivation center (Xic) is now dominated by large noncoding RNAs (ncRNA). X chromosome inactivation (XCI) equalizes gene expression between mammalian males and females by inactivating one X in female cells. XCI requires Xist, an ncRNA that coats the X and recruits Polycomb proteins. How Xist is controlled remains unclear but likely involves negative and positive regulators. For the active X, the antisense Tsix RNA is an established Xist repressor. For the inactive X, here, we identify Xic-encoded Jpx as an Xist activator. Jpx is developmentally regulated and accumulates during XCI. Deleting Jpx blocks XCI and is female lethal. Posttranscriptional Jpx knockdown recapitulates the knockout, and supplying Jpx in trans rescues lethality. Thus, Jpx is trans-acting and functions as ncRNA. Furthermore, Delta Jpx is rescued by truncating Tsix, indicating an antagonistic relationship between the ncRNAs. We conclude that Xist is controlled by two RNA-based switches: Tsix for Xa and Jpx for Xi. C1 [Tian, Di; Sun, Sha; Lee, Jeannie T.] Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. [Tian, Di; Sun, Sha; Lee, Jeannie T.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02115 USA. [Tian, Di; Sun, Sha; Lee, Jeannie T.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Tian, Di; Lee, Jeannie T.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. RP Lee, JT (reprint author), Massachusetts Gen Hosp, Howard Hughes Med Inst, Boston, MA 02115 USA. EM lee@molbio.mgh.harvard.edu FU NIH [K08-HD053824, RO1-GM58839]; [T32-CA009216] FX We thank Y. Jeon for providing Xist riboprobes, and A. Chess, D. Lessing, B. Payer, and S. Pinter for critical reading of the manuscript and all members of the laboratory for their helpful input throughout this project. This work was funded by NIH grants K08-HD053824 to D.T., RO1-GM58839 to J.T.L., and a Pathology training grant T32-CA009216. J.T.L. is also an Investigator of the Howard Hughes Medical Institute. NR 63 TC 204 Z9 224 U1 3 U2 36 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD OCT 29 PY 2010 VL 143 IS 3 BP 390 EP 403 DI 10.1016/j.cell.2010.09.049 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 672RF UT WOS:000283603900013 PM 21029862 ER PT J AU Bai, JH Hu, ZT Dittman, JS Pym, ECG Kaplan, JM AF Bai, Jihong Hu, Zhitao Dittman, Jeremy S. Pym, Edward C. G. Kaplan, Joshua M. TI Endophilin Functions as a Membrane-Bending Molecule and Is Delivered to Endocytic Zones by Exocytosis SO CELL LA English DT Article ID SYNAPTIC VESICLE ENDOCYTOSIS; NEUROTRANSMITTER RELEASE; CAENORHABDITIS-ELEGANS; NERVE-TERMINALS; PLASMA-MEMBRANE; BAR PROTEINS; C-ELEGANS; CURVATURE; TRANSMISSION; SYNAPTOJANIN AB Two models have been proposed for endophilin function in synaptic vesicle (SV) endocytosis. The scaffolding model proposes that endophilin's SH3 domain recruits essential endocytic proteins, whereas the membrane-bending model proposes that the BAR domain induces positively curved membranes. We show that mutations disrupting the scaffolding function do not impair endocytosis, whereas those disrupting membrane bending cause significant defects. By anchoring endophilin to the plasma membrane, we show that endophilin acts prior to scission to promote endocytosis. Despite acting at the plasma membrane, the majority of endophilin is targeted to the SV pool. Photoactivation studies suggest that the soluble pool of endophilin at synapses is provided by unbinding from the adjacent SV pool and that the unbinding rate is regulated by exocytosis. Thus, endophilin participates in an association-dissociation cycle with SVs that parallels the cycle of exo- and endocytosis. This endophilin cycle may provide a mechanism for functionally coupling endocytosis and exocytosis. C1 [Bai, Jihong; Hu, Zhitao; Pym, Edward C. G.; Kaplan, Joshua M.] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. [Bai, Jihong; Hu, Zhitao; Pym, Edward C. G.; Kaplan, Joshua M.] Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA. [Dittman, Jeremy S.] Weill Cornell Med Coll, Dept Biochem, New York, NY 10065 USA. RP Kaplan, JM (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM kaplan@molbio.mgh.harvard.edu RI hu, zhitao/H-5626-2011; OI Dittman, Jeremy S./0000-0002-3850-9078 FU Jane Coffin Childs postdoctoral fellowship; NIH [GM54728, K99MH085039] FX We thank the following for strains and reagents: Roger Tsien, Jennifer Lippincott-Schwartz, and the C. elegans Genetics Stock Center. We thank members of the Kaplan lab and Susana Garcia for critical comments. This work was supported by a Jane Coffin Childs postdoctoral fellowship (J.B.) and by NIH grants GM54728 (J.M.K.) and K99MH085039 (J.B.). NR 33 TC 53 Z9 53 U1 2 U2 18 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD OCT 29 PY 2010 VL 143 IS 3 BP 430 EP 441 DI 10.1016/j.cell.2010.09.024 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 672RF UT WOS:000283603900016 PM 21029864 ER PT J AU Desronvil, T Logan-Wyatt, D Abdrabou, W Triana, M Jones, R Taheri, S Del Bono, E Pasquale, LR Olivier, M Haines, JL Fan, BJ Wiggs, JL AF Desronvil, T. Logan-Wyatt, D. Abdrabou, W. Triana, M. Jones, R. Taheri, S. Del Bono, E. Pasquale, L. R. Olivier, M. Haines, J. L. Fan, B. J. Wiggs, J. L. TI Distribution of COL8A2 and COL8A1 gene variants in Caucasian primary open angle glaucoma patients with thin central corneal thickness SO MOLECULAR VISION LA English DT Article ID TO-DISC RATIO; INTRAOCULAR-PRESSURE; ENDOTHELIAL DYSTROPHY; MISSENSE MUTATIONS; RISK-FACTOR; TWIN EYE; HERITABILITY; CUP; ASSOCIATION; PROGRESSION AB Purpose: One approach to identify genes that contribute to common complex ocular disorders such as primary open angle glaucoma (POAG) is to study the genetic determinates of endophenotypes that are defined by underlying pre-disposing heritable quantitative traits such as central corneal thickness (CCT). Collagen VIII is a major component of Descemet's membrane and studies in mice have indicated that targeted inactivation of the genes encoding the collagen type 8 alpha1 (Col8a1) and collagen type 8 alpha2 (Col8a2) subunits (COL8A1 and COL8A2) results in thinning of the corneal stroma and of Descemet's membrane. The purpose of this study is to evaluate COL8A1 and COL8A2 as candidate genes for thin CCT in human POAG patients. Methods: 100 Caucasian POAG patients were enrolled in this study. The entire COL8A1 and COL8A2 coding sequence was determined in 8 patients with CCT<513 mu m (one standard deviation (36 microns) below the mean (550 microns) and 8 patients with CCT>586 mu m (one standard deviation above the mean). Selected COL8A2 exons containing variants of interest were sequenced in the full POAG cohort. Association and quantitative trait analyses were performed. Results: Three patients with CCT less than 513 mu m and advanced POAG were found to have missense changes in COL8A2; two patients had a previously identified mutation, R155Q and one had a novel change, P678L (p=0.0035, Fisher's exact test). Missense changes were not found in any of the patients with CCT>513 mu m and missense changes in the COL8A1 gene were not found in any patient. One common COL8A2 SNP, rs274754 was also statistically associated with CCT (p=0.018). Conclusions: In this study we have identified COL8A2 missense changes in a group of Caucasian patients with very thin CCT and advanced POAG. These results suggest that DNA sequence variants in the COL8A2 gene may be associated with thin corneas in some glaucoma patients. Further study of COL8A2 variants in other patient populations, especially those with thinner CCT such as African-Americans would provide further support for a role of COL8A2 in corneal thickness and in glaucoma. C1 [Desronvil, T.; Logan-Wyatt, D.; Abdrabou, W.; Triana, M.; Jones, R.; Taheri, S.; Del Bono, E.; Pasquale, L. R.; Fan, B. J.; Wiggs, J. L.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, Boston, MA 02114 USA. [Olivier, M.] Rosalind Franklin Univ Med & Sci, Chicago, IL USA. [Haines, J. L.] Vanderbilt Univ Sch Med, Ctr Human Genet Res, Nashville, TN USA. RP Wiggs, JL (reprint author), Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM janey_wiggs@meei.harvard.edu RI Haines, Jonathan/C-3374-2012; OI Fan, Baojian/0000-0002-6851-2737 FU NIH/NEI [EY015872, P30 EY014104]; Massachusetts Lions Eye Research Fund; Research to Prevent Blindness FX Supported in part by NIH/NEI grants EY015872 and P30 EY014104, the Massachusetts Lions Eye Research Fund and Research to Prevent Blindness. NR 40 TC 21 Z9 21 U1 1 U2 2 PU MOLECULAR VISION PI ATLANTA PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E, ATLANTA, GA 30322 USA SN 1090-0535 J9 MOL VIS JI Mol. Vis. PD OCT 29 PY 2010 VL 16 IS 234-36 BP 2185 EP 2191 PG 7 WC Biochemistry & Molecular Biology; Ophthalmology SC Biochemistry & Molecular Biology; Ophthalmology GA 674FD UT WOS:000283718900001 PM 21139683 ER PT J AU Chen, XY Kim, P Farinelli, B Doukas, A Yun, SH Gelfand, JA Anderson, RR Wu, MX AF Chen, Xinyuan Kim, Pilhan Farinelli, Bill Doukas, Apostolos Yun, Seok-Hyun Gelfand, Jeffrey A. Anderson, Richard R. Wu, Mei X. TI A Novel Laser Vaccine Adjuvant Increases the Motility of Antigen Presenting Cells SO PLOS ONE LA English DT Article ID ANTHRAX VACCINE; IMMUNIZATION; ANTIBODIES; RESPONSES; DELIVERY; SQUALENE; THERAPY AB Background: Development of a potent vaccine adjuvant without introduction of any side effects remains an unmet challenge in the field of the vaccine research. Methodology/Principal Findings: We found that laser at a specific setting increased the motility of antigen presenting cells (APCs) and immune responses, with few local or systemic side effects. This laser vaccine adjuvant (LVA) effect was induced by brief illumination of a small area of the skin or muscle with a nondestructive, 532 nm green laser prior to intradermal (i.d.) or intramuscular (i.m.) administration of vaccines at the site of laser illumination. The pre-illumination accelerated the motility of APCs as shown by intravital confocal microscopy, leading to sufficient antigen (Ag)-uptake at the site of vaccine injection and transportation of the Ag-captured APCs to the draining lymph nodes. As a result, the number of Ag+ dendritic cells (DCs) in draining lymph nodes was significantly higher in both the 1 degrees and 2 degrees draining lymph nodes in the presence than in the absence of LVA. Laser-mediated increases in the motility and lymphatic transportation of APCs augmented significantly humoral immune responses directed against a model vaccine ovalbumin (OVA) or influenza vaccine i.d. injected in both primary and booster vaccinations as compared to the vaccine itself. Strikingly, when the laser was delivered by a hair-like diffusing optical fiber into muscle, laser illumination greatly boosted not only humoral but also cell-mediated immune responses provoked by i.m. immunization with OVA relative to OVA alone. Conclusion/Significance: The results demonstrate the ability of this safe LVA to augment both humoral and cell-mediated immune responses. In comparison with all current vaccine adjuvants that are either chemical compounds or biological agents, LVA is novel in both its form and mechanism; it is risk-free and has distinct advantages over traditional vaccine adjuvants. C1 [Chen, Xinyuan; Kim, Pilhan; Farinelli, Bill; Doukas, Apostolos; Yun, Seok-Hyun; Anderson, Richard R.; Wu, Mei X.] Harvard Univ, Sch Med, Dept Dermatol, Wellman Ctr Photomed,Massachusetts Gen Hosp, Boston, MA 02115 USA. [Gelfand, Jeffrey A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. [Anderson, Richard R.; Wu, Mei X.] Harvard MIT Div Hlth Sci & Technol, Boston, MA USA. RP Chen, XY (reprint author), Harvard Univ, Sch Med, Dept Dermatol, Wellman Ctr Photomed,Massachusetts Gen Hosp, Boston, MA 02115 USA. EM mwu2@partners.org RI Kim, Pilhan/C-1836-2011 OI Kim, Pilhan/0000-0001-8388-1840 FU National Institutes of Health [AI070785, RC1 DA028378]; Boston Biocom LLC. [2008A2565]; Bill and Melinda Gates Foundation [53273] FX This work is supported in part by the National Institutes of Health grants AI070785 and RC1 DA028378, Sponsored Research agreement grant #2008A25652 from Boston Biocom LLC., and Grand Challenges Explorations grant #53273 from the Bill and Melinda Gates Foundation (to M.X.W.). As Boston Biocom partially employed J.G., Boston Biocom did play a role in data analysis and preparation of the manuscript. Other funders had no role in the study design, data analysis, preparation of the manuscript and the decision to publish or preparation of the manuscript. NR 28 TC 27 Z9 27 U1 2 U2 16 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 OCT 29 PY 2010 VL 5 IS 10 AR e13776 DI 10.1371/journal.pone.0013776 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 673FU UT WOS:000283645300050 PM 21048884 ER PT J AU Hui, KKS Marina, O Liu, J Rosen, BR Kwong, KK AF Hui, Kathleen K. S. Marina, Ovidiu Liu, Jing Rosen, Bruce R. Kwong, Kenneth K. TI Acupuncture, the limbic system, and the anticorrelated networks of the brain SO AUTONOMIC NEUROSCIENCE-BASIC & CLINICAL LA English DT Article DE Acupuncture; fMRI; Limbic-paralimbic-neocortical network; Default mode network; Deqi; Amygdala ID TREATMENT-RESISTANT DEPRESSION; STATE FUNCTIONAL CONNECTIVITY; RESTING-STATE; DEFAULT-MODE; ALZHEIMERS-DISEASE; DOPAMINE RELEASE; MAJOR DEPRESSION; CINGULATE CORTEX; HEALTHY-SUBJECTS; NOXIOUS HEAT AB The study of the mechanism of acupuncture action was revolutionized by the use of functional magnetic resonance imaging (fMRI). Over the past decade, our fMRI studies of healthy subjects have contributed substantially to elucidating the central effect of acupuncture on the human brain. These studies have shown that acupuncture stimulation, when associated with sensations comprising deqi, evokes deactivation of a limbic-paralimbic-neocortical network, which encompasses the limbic system, as well as activation of somatosensory brain regions. These networks closely match the default mode network and the anti-correlated task-positive network described in the literature. We have also shown that the effect of acupuncture on the brain is integrated at multiple levels, down to the brainstem and cerebellum. Our studies support the hypothesis that the effect of acupuncture on the brain goes beyond the effect of attention on the default mode network or the somatosensory stimulation of acupuncture needling. The amygdala and hypothalamus, in particular, show decreased activation during acupuncture stimulation that is not commonly associated with default mode network activity. At the same time, our research shows that acupuncture stimulation needs to be done carefully, limiting stimulation when the resulting sensations are very strong or when sharp pain is elicited. When acupuncture induced sharp pain, our studies show that the deactivation was attenuated or reversed in direction. Our results suggest that acupuncture mobilizes the functionally anti-correlated networks of the brain to mediate its actions, and that the effect is dependent on the psychophysical response. In this work we also discuss multiple avenues of future research, including the role of neurotransmitters, the effect of different acupuncture techniques, and the potential clinical application of our research findings to disease states including chronic pain, major depression, schizophrenia, autism, and Alzheimer's disease. Published by Elsevier B.V. C1 [Hui, Kathleen K. S.; Liu, Jing; Rosen, Bruce R.; Kwong, Kenneth K.] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, Charlestown, MA 02129 USA. [Hui, Kathleen K. S.; Liu, Jing; Rosen, Bruce R.; Kwong, Kenneth K.] Harvard Univ, Charlestown, MA USA. [Marina, Ovidiu] William Beaumont Hosp, Transit Year Program, Royal Oak, MI 48072 USA. RP Hui, KKS (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Dept Radiol, 149 13th St, Charlestown, MA 02129 USA. EM hui@nmr.mgh.harvard.edu FU NIH/National Center for Complementary and Alternative Medicine [R21-AT00978, 1-P01-AT002048-01, 2-P01-AT002048-06, K01-AT-002166-01, F05-AT003770]; National Center for Research Resources [P41RR14075]; Mental Illness and Neuroscience Discovery Institute; Brain Project [NS 34189] FX The work was supported in part by the NIH/National Center for Complementary and Alternative Medicine (R21-AT00978) (1-P01-AT002048-01) (2-P01-AT002048-06) (K01-AT-002166-01), (F05-AT003770), the National Center for Research Resources (P41RR14075), the Mental Illness and Neuroscience Discovery Institute and the Brain Project Grant NS 34189. We wish to thank Nikos Makris for consultations on neuroanatomy, and Randy Buckner for useful discussions on the default mode system. There are no conflicts of interest for any author. NR 94 TC 57 Z9 67 U1 3 U2 42 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1566-0702 J9 AUTON NEUROSCI-BASIC JI Auton. Neurosci-Basic Clin. PD OCT 28 PY 2010 VL 157 IS 1-2 SI SI BP 81 EP 90 DI 10.1016/j.autneu.2010.03.022 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 679SX UT WOS:000284182200015 PM 20494627 ER PT J AU Cutler, C AF Cutler, Corey TI Transplant survivorship: a call to arms SO BLOOD LA English DT Editorial Material ID LONG-TERM SURVIVORS; HEMATOPOIETIC-CELL TRANSPLANTATION C1 Dana Farber Canc Inst, Boston, MA 02115 USA. RP Cutler, C (reprint author), Dana Farber Canc Inst, Boston, MA 02115 USA. NR 9 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 OCT 28 PY 2010 VL 116 IS 17 BP 3126 EP 3127 DI 10.1182/blood-2010-08-299420 PG 4 WC Hematology SC Hematology GA 672LE UT WOS:000283583700006 PM 21030570 ER PT J AU Gorgun, G Calabrese, E Soydan, E Hideshima, T Perrone, G Bandi, M Cirstea, D Santo, L Hu, YG Tai, YT Nahar, S Mimura, N Fabre, C Raje, N Munshi, N Richardson, P Anderson, KC AF Goerguen, Guellue Calabrese, Elisabetta Soydan, Ender Hideshima, Teru Perrone, Giulia Bandi, Madhavi Cirstea, Diana Santo, Loredana Hu, Yiguo Tai, Yu-Tzu Nahar, Sabikun Mimura, Naoya Fabre, Claire Raje, Noopur Munshi, Nikhil Richardson, Paul Anderson, Kenneth C. TI Immunomodulatory effects of lenalidomide and pomalidomide on interaction of tumor and bone marrow accessory cells in multiple myeloma SO BLOOD LA English DT Article ID CYTOKINE SIGNAL-TRANSDUCTION; JAK-STAT; IN-VIVO; POTENT INHIBITORS; TNF-ALPHA; T-CELLS; B-CELLS; SUPPRESSOR; PATHWAY; IMMUNITY AB The bone marrow (BM) microenvironment consists of extracellular-matrix and the cellular compartment including immune cells. Multiple myeloma (MM) cell and BM accessory cell interaction promotes MM survival via both cell-cell contact and cytokines. Immunomodulatory agents (IMiDs) target not only MM cells, but also MM cell-immune cell interactions and cytokine signaling. Here we examined the in vitro effects of IMiDs on cytokine signaling triggered by interaction of effector cells with MM cells and BM stroma cells. IMiDs diminished interleukin-2, interferon gamma, and IL-6 regulator suppressor of cytokine signaling (SOCS) 1 expression in immune (CD4T, CD8T, natural-killer T, natural-killer) cells from both BM and PB of MM patients. In addition, coculture of MM cells with healthy PBMCs induced SOCS1 expression in effector cells; conversely, treatment with IMiDs down-regulated the SOCS1 expression. SOCS1 negatively regulates IL-6 signaling and is silenced by hypermethylation in MM cells. To define the mechanism of inhibitory-cytokine signaling in effector cells and MM cells, we next analyzed the interaction of immune cells with MM cells that were epigenetically modified to re-express SOCS1; IMiDs induced more potent CTL responses against SOCS1 re-expressing-MM cells than unmodified MM cells. These data therefore demonstrate that modulation of SOCS1 may enhance immune response and efficacy of IMiDs in MM. (Blood. 2010;116(17):3227-3237) C1 [Goerguen, Guellue; Calabrese, Elisabetta; Soydan, Ender; Hideshima, Teru; Perrone, Giulia; Bandi, Madhavi; Cirstea, Diana; Santo, Loredana; Hu, Yiguo; Tai, Yu-Tzu; Nahar, Sabikun; Mimura, Naoya; Fabre, Claire; Munshi, Nikhil; Richardson, Paul; Anderson, Kenneth C.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Raje, Noopur] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Munshi, Nikhil] Boston Vet Adm VA Hlth Care Syst, Boston, MA USA. RP Gorgun, G (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St,Rm M557, Boston, MA 02115 USA. EM gullu_gorgun@dfci.harvard.edu FU National Institutes of Health/National Cancer Institute (NIH/NCI) [P50 CA100707, P01 CA78378, R01 CA50947] FX This study was supported by National Institutes of Health/National Cancer Institute (NIH/NCI) Specialized Program of Research Excellence in Myeloma P50 CA100707 (K. C. A.); NIH/NCI Host-Tumor Cell Interactions in Myeloma: Therapeutic Applications P01 CA78378 (K. C. A.), and NIH/NCI Molecular Sequelae of Myeloma-Bone Marrow Interactions: Therapeutic Applications R01 CA50947 (K. C. A.) grants. Lenalidomide and pomalidomide were provided by Celgene. NR 50 TC 88 Z9 91 U1 0 U2 7 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD OCT 28 PY 2010 VL 116 IS 17 BP 3227 EP 3237 DI 10.1182/blood-2010-04-279893 PG 11 WC Hematology SC Hematology GA 672LE UT WOS:000283583700018 PM 20651070 ER PT J AU Green, MR Monti, S Rodig, SJ Juszczynski, P Currie, T O'Donnell, E Chapuy, B Takeyama, K Neuberg, D Golub, TR Kutok, JL Shipp, MA AF Green, Michael R. Monti, Stefano Rodig, Scott J. Juszczynski, Przemyslaw Currie, Treeve O'Donnell, Evan Chapuy, Bjoern Takeyama, Kunihiko Neuberg, Donna Golub, Todd R. Kutok, Jeffery L. Shipp, Margaret A. TI Integrative analysis reveals selective 9p24.1 amplification, increased PD-1 ligand expression, and further induction via JAK2 in nodular sclerosing Hodgkin lymphoma and primary mediastinal large B-cell lymphoma SO BLOOD LA English DT Article ID CIRCULAR BINARY SEGMENTATION; COSTIMULATORY MOLECULE; CLINICAL-SIGNIFICANCE; PANCREATIC-CANCER; IFN-GAMMA; B7-H1; IMBALANCES; GALECTIN-1; CARCINOMA; RESPONSES AB Classical Hodgkin lymphoma (cHL) and mediastinal large B-cell lymphoma (MLBCL) are lymphoid malignancies with certain shared clinical, histologic, and molecular features. Primary cHLs and MLBCLs include variable numbers of malignant cells within an inflammatory infiltrate, suggesting that these tumors escape immune surveillance. Herein, we integrate high-resolution copy number data with transcriptional profiles and identify the immunoregulatory genes, PD-L1 and PD-L2, as key targets at the 9p24.1 amplification peak in HL and MLBCL cell lines. We extend these findings to laser-capture microdissected primary Hodgkin Reed-Sternberg cells and primary MLB-CLs and find that programmed cell death-1 (PD-1) ligand/9p24.1 amplification is restricted to nodular sclerosing HL, the cHL subtype most closely related to MLBCL. Using quantitative immunohistochemical methods, we document the association between 9p24.1 copy number and PD-1 ligand expression in primary tumors. In cHL and MLBCL, the extended 9p24.1 amplification region also included the Janus kinase 2 (JAK2) locus. Of note, JAK2 amplification increased protein expression and activity, specifically induced PD-1 ligand transcription and enhanced sensitivity to JAK2 inhibition. Therefore, 9p24.1 amplification is a disease-specific structural alteration that increases both the gene dosage of PD-1 ligands and their induction by JAK2, defining the PD-1 pathway and JAK2 as complementary rational therapeutic targets. (Blood. 2010;116(17):3268-3277) C1 [Green, Michael R.; Juszczynski, Przemyslaw; O'Donnell, Evan; Chapuy, Bjoern; Takeyama, Kunihiko; Shipp, Margaret A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Monti, Stefano; Golub, Todd R.] Broad Inst, Cambridge, MA USA. [Rodig, Scott J.; Currie, Treeve; Kutok, Jeffery L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Neuberg, Donna] Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. RP Shipp, MA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM margaret_shipp@dfci.harvard.edu RI Green, Michael/F-3482-2013; OI Green, Michael/0000-0001-6309-9472; Monti, Stefano/0000-0002-9376-0660 FU National Institutes of Health [PO1 CA092625]; Miller Family Research Fund FX This work was supported by funding from the National Institutes of Health (PO1 CA092625) and the Miller Family Research Fund. NR 50 TC 287 Z9 294 U1 5 U2 17 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD OCT 28 PY 2010 VL 116 IS 17 BP 3268 EP 3277 DI 10.1182/blood-2010-05-282780 PG 10 WC Hematology SC Hematology GA 672LE UT WOS:000283583700022 PM 20628145 ER PT J AU Verzi, MP Shivdasani, RA AF Verzi, Michael P. Shivdasani, Ramesh A. TI STEM CELLS The intestinal-crypt casino SO NATURE LA English DT Editorial Material ID LGR5 C1 [Verzi, Michael P.; Shivdasani, Ramesh A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Verzi, Michael P.; Shivdasani, Ramesh A.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Verzi, Michael P.; Shivdasani, Ramesh A.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Verzi, MP (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. EM ramesh_shivdasani@dfci.harvard.edu FU NIDDK NIH HHS [K01 DK088868] NR 10 TC 4 Z9 4 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD OCT 28 PY 2010 VL 467 IS 7319 BP 1055 EP 1056 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 671XW UT WOS:000283548600036 PM 20981089 ER PT J AU Altshuler, D Durbin, RM Abecasis, GR Bentley, DR Chakravarti, A Clark, AG Collins, FS De la Vega, FM Donnelly, P Egholm, M Flicek, P Gabriel, SB Gibbs, RA Knoppers, BM Lander, ES Lehrach, H Mardis, ER McVean, GA Nickerson, D Peltonen, L Schafer, AJ Sherry, ST Wang, J Wilson, RK Gibbs, RA Deiros, D Metzker, M Muzny, D Reid, J Wheeler, D Wang, J Li, JX Jian, M Li, G Li, RQ Liang, HQ Tian, G Wang, B Wang, J Wang, W Yang, HM Zhang, XQ Zheng, HS Lander, ES Altshuler, DL Ambrogio, L Bloom, T Cibulskis, K Fennell, TJ Gabriel, SB Jaffe, DB Shefler, E Sougnez, CL Bentley, DR Gormley, N Humphray, S Kingsbury, Z Koko-Gonzales, P Stone, J McKernan, KJ Costa, GL Ichikawa, JK Lee, CC Sudbrak, R Lehrach, H Borodina, TA Dahl, A Davydov, AN Marquardt, P Mertes, F Nietfeld, W Rosenstiel, P Schreiber, S Soldatov, AV Timmermann, B Tolzmann, M Egholm, M Affourtit, J Ashworth, D Attiya, S Bachorski, M Buglione, E Burke, A Caprio, A Celone, C Clark, S Conners, D Desany, B Gu, L Guccione, L Kao, K Kebbel, A Knowlton, J Labrecque, M McDade, L Mealmaker, C Minderman, M Nawrocki, A Niazi, F Pareja, K Ramenani, R Riches, D Song, W Turcotte, C Wang, S Mardis, ER Dooling, D Fulton, L Fulton, R Weinstock, G Durbin, RM Burton, J Carter, DM Churcher, C Coffey, A Cox, A Palotie, A Quail, M Skelly, T Stalker, J Swerdlow, HP Turner, D De Witte, A Giles, S Gibbs, RA Wheeler, D Bainbridge, M Challis, D Sabo, A Yu, F Yu, J Wang, J Fang, XD Guo, XS Li, RQ Li, YR Luo, RB Tai, S Wu, HL Zheng, HC Zheng, XL Zhou, Y Yang, HM Marth, GT Garrison, EP Huang, W Indap, A Kural, D Lee, WP Leong, WF Huang, WC Indap, A Kural, D Lee, WP Leong, WF Quinlan, AR Stewart, C Stromberg, MP Ward, AN Wu, JT Lee, C Mills, RE Shi, XH Daly, MJ DePristo, MA Altshuler, DL Ball, AD Banks, E Bloom, T Browning, BL Cibulskis, K Fennell, TJ Garimella, KV Grossman, SR Handsaker, RE Hanna, M Hartl, C Jaffe, DB Kernytsky, AM Korn, JM Li, H Maguire, JR McCarroll, SA McKenna, A Nemesh, JC Philippakis, AA Poplin, RE Price, A Rivas, MA Sabeti, PC Schaffner, SF Shefler, E Shlyakhter, IA Cooper, DN Ball, EV Mort, M Phillips, AD Stenson, PD Sebat, J Makarov, V Ye, K Yoon, SC Bustamante, CD Clark, AG Boyko, A Degenhardt, J Gravel, S Gutenkunst, RN Kaganovich, M Keinan, A Lacroute, P Ma, X Reynolds, A Clarke, L Flicek, P Cunningham, F Herrero, J Keenen, S Kulesha, E Leinonen, R McLaren, W Radhakrishnan, R Smith, RE Zalunin, V Zheng-Bradley, XQ Korbel, JO Stutz, AM Humphray, S Bauer, M Cheetham, RK Cox, T Eberle, M James, T Kahn, S Murray, L Ye, K De La Vega, FM Fu, YT Hyland, FCL Manning, JM McLaughlin, SF Peckham, HE Sakarya, O Sun, YA Tsung, EF Batzer, MA Konkel, MK Walker, JA Sudbrak, R Albrecht, MW Amstislavskiy, VS Herwig, R Parkhomchuk, DV Sherry, ST Agarwala, R Khouri, H Morgulis, AO Paschall, JE Phan, LD Rotmistrovsky, KE Sanders, RD Shumway, MF Xiao, CL McVean, GA Auton, A Iqbal, Z Lunter, G Marchini, JL Moutsianas, L Myers, S Tumian, A Desany, B Knight, J Winer, R Craig, DW Beckstrom-Sternberg, SM Christoforides, A Kurdoglu, AA Pearson, J Sinari, SA Tembe, WD Haussler, D Hinrichs, AS Katzman, SJ Kern, A Kuhn, RM Przeworski, M Hernandez, RD Howie, B Kelley, JL Melton, SC Abecasis, GR Li, Y Anderson, P Blackwell, T Chen, W Cookson, WO Ding, J Kang, HM Lathrop, M Liang, LM Moffatt, MF Scheet, P Sidore, C Snyder, M Zhan, XW Zollner, S Awadalla, P Casals, F Idaghdour, Y Keebler, J Stone, EA Zilversmit, M Jorde, L Xing, JC Eichler, EE Aksay, G Alkan, C Hajirasouliha, I Hormozdiari, F Kidd, JM Sahinalp, SC Sudmant, PH Mardis, ER Chen, K Chinwalla, A Ding, L Koboldt, DC McLellan, MD Dooling, D Weinstock, G Wallis, JW Wendl, MC Zhang, QY Durbin, RM Albers, CA Ayub, Q Balasubramaniam, S Barrett, JC Carter, DM Chen, YA Conrad, DF Danecek, P Dermitzakis, ET Hu, M Huang, N Hurles, ME Jin, HJ Jostins, L Keane, TM Keane, TM Le, SQ Lindsay, S Long, QA MacArthur, DG Montgomery, SB Parts, L Stalker, J Tyler-Smith, C Walter, K Zhang, YJ Gerstein, MB Snyder, M Abyzov, A Abyzov, A Balasubramanian, S Bjornson, R Du, JA Grubert, F Habegger, L Haraksingh, R Jee, J Khurana, E Lam, HYK Leng, J Mu, XJ Urban, AE Zhang, ZD Li, YR Luo, RB Marth, GT Garrison, EP Kural, D Quinlan, AR Stewart, C Stromberg, MP Ward, AN Wu, JT Lee, C Mills, RE Shi, XH McCarroll, SA Banks, E DePristo, MA Handsaker, RE Hartl, C Korn, JM Li, H Nemesh, JC Sebat, J Makarov, V Ye, K Yoon, SC Degenhardt, J Kaganovich, M Clarke, L Smith, RE Zheng-Bradley, XQ Korbel, JO Humphray, S Cheetham, RK Eberle, M Kahn, S Murray, L Ye, K De la Vega, FM Fu, YT Peckham, HE Sun, YA Batzer, MA Konkel, MK Xiao, CL Iqbal, Z Desany, B Blackwell, T Snyder, M Xing, JC Eichler, EE Aksay, G Alkan, C Hajirasouliha, I Hormozdiari, F Kidd, JM Chen, K Chinwalla, A Ding, L McLellan, MD Wallis, JW Hurles, ME Conrad, DF Walter, K Zhang, YJ Gerstein, MB Snyder, M Abyzov, A Du, JA Grubert, F Haraksingh, R Jee, J Khurana, E Lam, HYK Leng, J Mu, XJ Urban, AE Zhang, ZD Gibbs, RA Bainbridge, M Challis, D Coafra, C Dinh, H Kovar, C Lee, S Muzny, D Nazareth, L Reid, J Sabo, A Yu, FL Yu, J Marth, GT Garrison, EP Indap, A Leong, WF Quinlan, AR Stewart, C Ward, AN Wu, JT Cibulskis, K Fennell, TJ Gabriel, SB Garimella, KV Hartl, C Shefler, E Sougnez, CL Wilkinson, J Clark, AG Gravel, S Grubert, F Clarke, L Flicek, P Smith, RE Zheng-Bradley, XQ Sherry, ST Khouri, HM Paschall, JE Shumway, MF Xiao, CL McVean, GA Katzman, SJ Abecasis, GR Blackwell, T Mardis, ER Dooling, D Fulton, L Fulton, R Koboldt, DC Durbin, RM Balasubramaniam, S Coffey, A Keane, TM MacArthur, DG Palotie, A Scott, C Stalker, J Tyler-Smith, C Gerstein, MB Balasubramanian, S Chakravarti, A Knoppers, BM Peltonen, L Abecasis, GR Bustamante, CD Gharani, N Gibbs, RA Jorde, L Kaye, JS Kent, A Li, T McGuire, AL McVean, GA Ossorio, PN Rotimi, CN Su, YY Toji, LH Tyler-Smith, C Brooks, LD Felsenfeld, AL McEwen, JE Abdallah, A Christopher, R Clemm, NC Collins, FS Duncanson, A Green, ED Guyer, MS Peterson, JL Schafer, AJ Abecasis, GR Altshuler, DL Auton, A Brooks, LD Durbin, RM Gibbs, RA Hurles, ME McVean, GA AF Altshuler, David Durbin, Richard M. Abecasis, Goncalo R. Bentley, David R. Chakravarti, Aravinda Clark, Andrew G. Collins, Francis S. De la Vega, Francisco M. Donnelly, Peter Egholm, Michael Flicek, Paul Gabriel, Stacey B. Gibbs, Richard A. Knoppers, Bartha M. Lander, Eric S. Lehrach, Hans Mardis, Elaine R. McVean, Gil A. Nickerson, DebbieA. Peltonen, Leena Schafer, Alan J. Sherry, Stephen T. Wang, Jun Wilson, Richard K. Gibbs, Richard A. Deiros, David Metzker, Mike Muzny, Donna Reid, Jeff Wheeler, David Wang, Jun Li, Jingxiang Jian, Min Li, Guoqing Li, Ruiqiang Liang, Huiqing Tian, Geng Wang, Bo Wang, Jian Wang, Wei Yang, Huanming Zhang, Xiuqing Zheng, Huisong Lander, Eric S. Altshuler, David L. Ambrogio, Lauren Bloom, Toby Cibulskis, Kristian Fennell, Tim J. Gabriel, Stacey B. Jaffe, David B. Shefler, Erica Sougnez, Carrie L. Bentley, David R. Gormley, Niall Humphray, Sean Kingsbury, Zoya Koko-Gonzales, Paula Stone, Jennifer McKernan, Kevin J. Costa, Gina L. Ichikawa, Jeffry K. Lee, Clarence C. Sudbrak, Ralf Lehrach, Hans Borodina, Tatiana A. Dahl, Andreas Davydov, Alexey N. Marquardt, Peter Mertes, Florian Nietfeld, Wilfiried Rosenstiel, Philip Schreiber, Stefan Soldatov, Aleksey V. Timmermann, Bernd Tolzmann, Marius Egholm, Michael Affourtit, Jason Ashworth, Dana Attiya, Said Bachorski, Melissa Buglione, Eli Burke, Adam Caprio, Amanda Celone, Christopher Clark, Shauna Conners, David Desany, Brian Gu, Lisa Guccione, Lorri Kao, Kalvin Kebbel, Andrew Knowlton, Jennifer Labrecque, Matthew McDade, Louise Mealmaker, Craig Minderman, Melissa Nawrocki, Anne Niazi, Faheem Pareja, Kristen Ramenani, Ravi Riches, David Song, Wanmin Turcotte, Cynthia Wang, Shally Mardis, Elaine R. Dooling, David Fulton, Lucinda Fulton, Robert Weinstock, George Durbin, Richard M. Burton, John Carter, David M. Churcher, Carol Coffey, Alison Cox, Anthony Palotie, Aarno Quail, Michael Skelly, Tom Stalker, James Swerdlow, Harold P. Turner, Daniel De Witte, Anniek Giles, Shane Gibbs, Richard A. Wheeler, David Bainbridge, Matthew Challis, Danny Sabo, Aniko Yu, Fuli Yu, Jin Wang, Jun Fang, Xiaodong Guo, Xiaosen Li, Ruiqiang Li, Yingrui Luo, Ruibang Tai, Shuaishuai Wu, Honglong Zheng, Hancheng Zheng, Xiaole Zhou, Yan Yang, Huanming Marth, Gabor T. Garrison, Erik P. Huang, Weichun Indap, Amit Kural, Deniz Lee, Wan-Ping Leong, Wen Fung Huang, Weichun Indap, Amit Kural, Deniz Lee, Wan-Ping Leong, Wen Fung Quinlan, Aaron R. Stewart, Chip Stromberg, Michael P. Ward, Alistair N. Wu, Jiantao Lee, Charles Mills, Ryan E. Shi, Xinghua Daly, Mark J. DePristo, Mark A. Altshuler, David L. Ball, Aaron D. Banks, Eric Bloom, Toby Browning, Brian L. Cibulskis, Kristian Fennell, Tim J. Garimella, Kiran V. Grossman, Sharon R. Handsaker, Robert E. Hanna, Matt Hartl, Chris Jaffe, David B. Kernytsky, Andrew M. Korn, Joshua M. Li, Heng Maguire, Jared R. McCarroll, Steven A. McKenna, Aaron Nemesh, James C. Philippakis, Anthony A. Poplin, Ryan E. Price, Alkes Rivas, Manuel A. Sabeti, Pardis C. Schaffner, Stephen F. Shefler, Erica Shlyakhter, Ilya A. Cooper, David N. Ball, Edward V. Mort, Matthew Phillips, Andrew D. Stenson, Peter D. Sebat, Jonathan Makarov, Vladimir Ye, Kenny Yoon, Seungtai C. Bustamante, Carlos D. Clark, Andrew G. Boyko, Adam Degenhardt, Jeremiah Gravel, Simon Gutenkunst, Ryan N. Kaganovich, Mark Keinan, Alon Lacroute, Phil Ma, Xia Reynolds, Andy Clarke, Laura Flicek, Paul Cunningham, Fiona Herrero, Javier Keenen, Stephen Kulesha, Eugene Leinonen, Rasko McLaren, WilliamM. Radhakrishnan, Rajesh Smith, Richard E. Zalunin, Vadim Zheng-Bradley, Xiangqun Korbel, Jan O. Stuetz, Adrian M. Humphray, Sean Bauer, Markus Cheetham, R. Keira Cox, Tony Eberle, Michael James, Terena Kahn, Scott Murray, Lisa Ye, Kai De La Vega, Francisco M. Fu, Yutao Hyland, Fiona C. L. Manning, Jonathan M. McLaughlin, Stephen F. Peckham, Heather E. Sakarya, Onur Sun, Yongming A. Tsung, Eric F. Batzer, Mark A. Konkel, Miriam K. Walker, Jerilyn A. Sudbrak, Ralf Albrecht, Marcus W. Amstislavskiy, Vyacheslav S. Herwig, Ralf Parkhomchuk, Dimitri V. Sherry, Stephen T. Agarwala, Richa Khouri, Hodam. Morgulis, Aleksandr O. Paschall, Justin E. Phan, Lon D. Rotmistrovsky, Kirill E. Sanders, Robert D. Shumway, Martin F. Xiao, Chunlin McVean, Gil A. Auton, Adam Iqbal, Zamin Lunter, Gerton Marchini, Jonathan L. Moutsianas, Loukas Myers, Simon Tumian, Afidalina Desany, Brian Knight, James Winer, Roger Craig, David W. Beckstrom-Sternberg, Steve M. Christoforides, Alexis Kurdoglu, Ahmet A. Pearson, Johnv. Sinari, Shripad A. Tembe, Waibhav D. Haussler, David Hinrichs, Angie S. Katzman, Sol J. Kern, Andrew Kuhn, Robert M. Przeworski, Molly Hernandez, Ryan D. Howie, Bryan Kelley, Joanna L. Melton, S. Cord Abecasis, Goncalo R. Li, Yun Anderson, Paul Blackwell, Tom Chen, Wei Cookson, William O. Ding, Jun Kang, Hyun Min Lathrop, Mark Liang, Liming Moffatt, Miriam F. Scheet, Paul Sidore, Carlo Snyder, Matthew Zhan, Xiaowei Zoellner, Sebastian Awadalla, Philip Casals, Ferran Idaghdour, Youssef Keebler, John Stone, Eric A. Zilversmit, Martine Jorde, Lynn Xing, Jinchuan Eichler, Evan E. Aksay, Gozde Alkan, Can Hajirasouliha, Iman Hormozdiari, Fereydoun Kidd, Jeffrey M. Sahinalp, S. Cenk Sudmant, Peter H. Mardis, Elaine R. Chen, Ken Chinwalla, Asif Ding, Li Koboldt, Daniel C. McLellan, Mike D. Dooling, David Weinstock, George Wallis, John W. Wendl, Michael C. Zhang, Qunyuan Durbin, Richard M. Albers, Cornelis A. Ayub, Qasim Balasubramaniam, Senduran Barrett, Jeffrey C. Carter, David M. Chen, Yuan Conrad, Donald F. Danecek, Petr Dermitzakis, Emmanouil T. Hu, Min Huang, Ni Hurles, Matt E. Jin, Hanjun Jostins, Luke Keane, Thomas M. Keane, Thomas M. Le, Si Quang Lindsay, Sarah Long, Quan MacArthur, Daniel G. Montgomery, Stephen B. Parts, Leopold Stalker, James Tyler-Smith, Chris Walter, Klaudia Zhang, Yujun Gerstein, Mark B. Snyder, Michael Abyzov, Alexej Abyzov, Alexej Balasubramanian, Suganthi Bjornson, Robert Du, Jiang Grubert, Fabian Habegger, Lukas Haraksingh, Rajini Jee, Justin Khurana, Ekta Lam, Hugo Y. K. Leng, Jing Mu, Xinmeng Jasmine Urban, Alexander E. Zhang, Zhengdong Li, Yingrui Luo, Ruibang Marth, Gabor T. Garrison, Erik P. Kural, Deniz Quinlan, Aaron R. Stewart, Chip Stromberg, Michael P. Ward, Alistair N. Wu, Jiantao Lee, Charles Mills, Ryan E. Shi, Xinghua McCarroll, Steven A. Banks, Eric DePristo, Mark A. Handsaker, Robert E. Hartl, Chris Korn, Joshua M. Li, Heng Nemesh, James C. Sebat, Jonathan Makarov, Vladimir Ye, Kenny Yoon, Seungtai C. Degenhardt, Jeremiah Kaganovich, Mark Clarke, Laura Smith, Richard E. Zheng-Bradley, Xiangqun Korbel, Jan O. Humphray, Sean Cheetham, R. Keira Eberle, Michael Kahn, Scott Murray, Lisa Ye, Kai De la Vega, Francisco M. Fu, Yutao Peckham, Heather E. Sun, Yongming A. Batzer, Mark A. Konkel, Miriam K. Xiao, Chunlin Iqbal, Zamin Desany, Brian Blackwell, Tom Snyder, Matthew Xing, Jinchuan Eichler, Evan E. Aksay, Gozde Alkan, Can Hajirasouliha, Iman Hormozdiari, Fereydoun Kidd, Jeffrey M. Chen, Ken Chinwalla, Asif Ding, Li McLellan, Mike D. Wallis, John W. Hurles, Matt E. Conrad, Donald F. Walter, Klaudia Zhang, Yujun Gerstein, Mark B. Snyder, Michael Abyzov, Alexej Du, Jiang Grubert, Fabian Haraksingh, Rajini Jee, Justin Khurana, Ekta Lam, Hugo Y. K. Leng, Jing Mu, Xinmeng Jasmine Urban, Alexander E. Zhang, Zhengdong Gibbs, Richard A. Bainbridge, Matthew Challis, Danny Coafra, Cristian Dinh, Huyen Kovar, Christie Lee, Sandy Muzny, Donna Nazareth, Lynne Reid, Jeff Sabo, Aniko Yu, Fuli Yu, Jin Marth, Gabor T. Garrison, Erik P. Indap, Amit Leong, Wen Fung Quinlan, Aaron R. Stewart, Chip Ward, Alistair N. Wu, Jiantao Cibulskis, Kristian Fennell, Tim J. Gabriel, Stacey B. Garimella, Kiran V. Hartl, Chris Shefler, Erica Sougnez, Carrie L. Wilkinson, Jane Clark, Andrew G. Gravel, Simon Grubert, Fabian Clarke, Laura Flicek, Paul Smith, Richard E. Zheng-Bradley, Xiangqun Sherry, Stephen T. Khouri, Hoda M. Paschall, Justin E. Shumway, Martin F. Xiao, Chunlin McVean, Gil A. Katzman, Sol J. Abecasis, Goncalo R. Blackwell, Tom Mardis, Elaine R. Dooling, David Fulton, Lucinda Fulton, Robert Koboldt, Daniel C. Durbin, Richard M. Balasubramaniam, Senduran Coffey, Allison Keane, Thomas M. MacArthur, Daniel G. Palotie, Aarno Scott, Carol Stalker, James Tyler-Smith, Chris Gerstein, Mark B. Balasubramanian, Suganthi Chakravarti, Aravinda Knoppers, Bartha M. Peltonen, Leena Abecasis, Goncalo R. Bustamante, Carlos D. Gharani, Neda Gibbs, Richard A. Jorde, Lynn Kaye, Jane S. Kent, Alastair Li, Taosha McGuire, Amy L. McVean, Gil A. Ossorio, Pilar N. Rotimi, Charles N. Su, Yeyang Toji, Lorraine H. Tyler-Smith, Chris Brooks, Lisa D. Felsenfeld, Adam L. McEwen, Jean E. Abdallah, Assya Juenger, Christopher R. Clemm, Nicholas C. Collins, Francis S. Duncanson, Audrey Green, Eric D. Guyer, Mark S. Peterson, Jane L. Schafer, Alan J. Abecasis, Goncalo R. Altshuler, David L. Auton, Adam Brooks, Lisa D. Durbin, Richard M. Gibbs, Richard A. Hurles, Matt E. McVean, Gil A. CA 1000 Genomes Project Consortium TI A map of human genome variation from population-scale sequencing SO NATURE LA English DT Article ID WIDE ASSOCIATION; GENE-EXPRESSION; RECOMBINATION HOTSPOTS; MEIOTIC RECOMBINATION; GENOTYPE IMPUTATION; RARE VARIANTS; HAPLOTYPE MAP; NUCLEOTIDE; DISEASES; COMMON AB The 1000 Genomes Project aims to provide a deep characterization of human genome sequence variation as a foundation for investigating the relationship between genotype and phenotype. Here we present results of the pilot phase of the project, designed to develop and compare different strategies for genome-wide sequencing with high-throughput platforms. We undertook three projects: low-coverage whole-genome sequencing of 179 individuals from four populations; high-coverage sequencing of two mother-father-child trios; and exon-targeted sequencing of 697 individuals from seven populations. We describe the location, allele frequency and local haplotype structure of approximately 15 million single nucleotide polymorphisms, 1 million short insertions and deletions, and 20,000 structural variants, most of which were previously undescribed. We show that, because we have catalogued the vast majority of common variation, over 95% of the currently accessible variants found in any individual are present in this data set. On average, each person is found to carry approximately 250 to 300 loss-of-function variants in annotated genes and 50 to 100 variants previously implicated in inherited disorders. We demonstrate how these results can be used to inform association and functional studies. From the two trios, we directly estimate the rate of de novo germline base substitution mutations to be approximately 10(-8) per base pair per generation. We explore the data with regard to signatures of natural selection, and identify a marked reduction of genetic variation in the neighbourhood of genes, due to selection at linked sites. These methods and public data will support the next phase of human genetic research. C1 [Gabriel, Stacey B.; Lander, Eric S.; Lander, Eric S.; Ambrogio, Lauren; Cibulskis, Kristian; Fennell, Tim J.; Jaffe, David B.; Shefler, Erica; Sougnez, Carrie L.; Daly, Mark J.; DePristo, Mark A.; Ball, Aaron D.; Banks, Eric; Bloom, Toby; Cibulskis, Kristian; Fennell, Tim J.; Garimella, Kiran V.; Handsaker, Robert E.; Hanna, Matt; Hartl, Chris; Jaffe, David B.; Kernytsky, Andrew M.; Korn, Joshua M.; Li, Heng; Maguire, Jared R.; McCarroll, Steven A.; McKenna, Aaron; Nemesh, James C.; Philippakis, Anthony A.; Poplin, Ryan E.; Rivas, Manuel A.; Sabeti, Pardis C.; Schaffner, Stephen F.; Fu, Yutao; Banks, Eric; DePristo, Mark A.; Hartl, Chris; Korn, Joshua M.; Nemesh, James C.; Garimella, Kiran V.; Sougnez, Carrie L.; Wilkinson, Jane; Altshuler, David L.] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA. 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[Marth, Gabor T.; Garrison, Erik P.; Indap, Amit; Kural, Deniz; Lee, Wan-Ping; Leong, Wen Fung; Stewart, Chip; Ward, Alistair N.; Wu, Jiantao] Boston Coll, Dept Biol, Chestnut Hill, MA 02467 USA. [Huang, Weichun] US Natl Inst Hlth, Natl Inst Environm Hlth Sci, Res Triangle Pk, NC 27709 USA. [Quinlan, Aaron R.] Univ Virginia, Sch Med, Dept Biochem & Mol Genet, Charlottesville, VA 22908 USA. [Stromberg, Michael P.] Illumina, San Diego, CA 92121 USA. [Lee, Charles; Mills, Ryan E.; Shi, Xinghua; Altshuler, David L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Shi, Xinghua; Altshuler, David L.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Browning, Brian L.] Univ Washington, Dept Med, Div Gen Med, Seattle, WA 98195 USA. [Grossman, Sharon R.; Sabeti, Pardis C.; Shlyakhter, Ilya A.] Harvard Univ, Ctr Syst Biol, Dept Organism & Evolut Biol, Cambridge, MA 02138 USA. [Price, Alkes] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Cooper, David N.; Ball, Edward V.; Mort, Matthew; Phillips, Andrew D.; Stenson, Peter D.] Cardiff Univ, Inst Med Genet, Cardiff CF14 4XN, Wales. [Sebat, Jonathan] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA. Univ Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USA. [Makarov, Vladimir] Mt Sinai Sch Med, Seaver Autism Ctr, New York, NY 10029 USA. [Makarov, Vladimir] Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. [Ye, Kenny] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10461 USA. [Yoon, Seungtai C.] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY 10029 USA. [Bustamante, Carlos D.; Boyko, Adam; Gravel, Simon; Kaganovich, Mark; Lacroute, Phil; Du, Jiang; Lam, Hugo Y. K.; Urban, Alexander E.; Kidd, Jeffrey M.; Snyder, Michael; Grubert, Fabian; Lam, Hugo Y. K.; Urban, Alexander E.] Stanford Univ, Dept Genet, Stanford, CA 94305 USA. [Gutenkunst, Ryan N.] Univ Arizona, Dept Mol & Cellular Biol, Tucson, AZ 85721 USA. [Korbel, Jan O.; Stuetz, Adrian M.] Genome Biol Res Unit, European Mol Biol Lab, D-69117 Heidelberg, Germany. [Ye, Kai] Leiden Univ Med Ctr, Mol Epidemiol Sect, NL-2333 ZA Leiden, Netherlands. [Batzer, Mark A.; Konkel, Miriam K.; Walker, Jerilyn A.] Louisiana State Univ, Dept Biol Sci, Baton Rouge, LA 70803 USA. [Craig, David W.; Beckstrom-Sternberg, Steve M.; Christoforides, Alexis; Kurdoglu, Ahmet A.; Pearson, Johnv.; Sinari, Shripad A.; Tembe, Waibhav D.] Translat Genom Res Inst, Phoenix, AZ 85004 USA. [Haussler, David; Hinrichs, Angie S.; Katzman, Sol J.; Kern, Andrew; Kuhn, Robert M.] Univ Calif Santa Cruz, Ctr Biomol Sci & Engn, Santa Cruz, CA 95064 USA. [Przeworski, Molly] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA. [Przeworski, Molly] Univ Chicago, Howard Hughes Med Inst, Chicago, IL 60637 USA. [Hernandez, Ryan D.; Howie, Bryan; Kelley, Joanna L.; Melton, S. Cord] Univ Calif San Francisco, Dept Bioengn & Therapeut Sci, San Francisco, CA 94158 USA. Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA. [Cookson, William O.; Moffatt, Miriam F.] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London SW7 2, England. [Lathrop, Mark] Ctr Natl Genotypage, F-91000 Evry, France. [Liang, Liming] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. [Liang, Liming] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Scheet, Paul] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. [Awadalla, Philip] Univ Montreal, Fac Med, Dept Pediat, Ste Justine Hosp Res Ctr, Montreal, PQ H3T IC5, Canada. [Casals, Ferran; Idaghdour, Youssef; Keebler, John; Stone, Eric A.; Zilversmit, Martine] Univ Montreal, Dept Med, Ctr Hosp, Univ Montreal Res Ctr, Montreal, PQ H2L 2W5, Canada. [Jorde, Lynn; Xing, Jinchuan; Xing, Jinchuan; Jorde, Lynn] Univ Utah, Sch Med, Eccles Inst Human Genet, Salt Lake City, UT 84112 USA. [Eichler, Evan E.; Alkan, Can; Alkan, Can] Univ Washington, Sch Med, Depat Genome Sci, Seattle, WA 98195 USA. [Eichler, Evan E.; Alkan, Can; Alkan, Can] Howard Hughes Med Inst, Seattle, WA 98195 USA. [Hajirasouliha, Iman; Hormozdiari, Fereydoun; Sahinalp, S. Cenk; Hajirasouliha, Iman; Hormozdiari, Fereydoun] Simon Fraser Univ, Dept Comp Sci, Burnaby, BC V5A 1S6, Canada. [Albers, Cornelis A.] Univ Cambridge, Dept Haematol, Cambridge CB2 1TN, England. [Albers, Cornelis A.] Natl Hlth Serv Blood & Transplant, Cambridge CB2 1TN, England. [Dermitzakis, Emmanouil T.; Montgomery, Stephen B.] Univ Geneva, Sch Med, Dept Genet Med & Dev, CH-1211 Geneva, Switzerland. [Jin, Hanjun] Korea Natl Inst Hlth, Ctr Genome Sci, Seoul 122701, South Korea. [Abyzov, Alexej; Habegger, Lukas; Haraksingh, Rajini; Gerstein, Mark B.; Abyzov, Alexej; Haraksingh, Rajini; Jee, Justin; Leng, Jing; Mu, Xinmeng Jasmine] Yale Univ, Program Computat Biol & Bioinformat, New Haven, CT 06520 USA. [Balasubramanian, Suganthi; Bjornson, Robert; Gerstein, Mark B.; Du, Jiang] Yale Univ, Dept Comp Sci, New Haven, CT 06520 USA. [Abyzov, Alexej; Khurana, Ekta; Urban, Alexander E.; Zhang, Zhengdong; Balasubramanian, Suganthi] Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT 06520 USA. [Urban, Alexander E.; Urban, Alexander E.] Stanford Univ, Dept Psychiat & Behav Studies, Stanford, CA 94305 USA. [Gharani, Neda; Toji, Lorraine H.] Corell Inst, Camden, NJ 08103 USA. [Kaye, Jane S.] Univ Oxford, Ctr Hlth Law & Emerging Technol, Oxford OX3 7LF, England. [Kent, Alastair] Genet Alliance, London N1 3QP, England. [McGuire, Amy L.] Baylor Coll Med, Ctr Med Eth & Hlth Policy, Houston, TX 77030 USA. [Ossorio, Pilar N.] Univ Wisconsin Madison, Dept Med Hist & Bioeth, Madison, WI 53706 USA. [Rotimi, Charles N.] US Natl Inst Hlth, Ctr Res Genom & Global Hlth, Bethesda, MD 20892 USA. [Brooks, Lisa D.; Felsenfeld, Adam L.; McEwen, Jean E.; Clemm, Nicholas C.; Green, Eric D.; Guyer, Mark S.; Peterson, Jane L.; Brooks, Lisa D.] US Natl Inst Hlth, NHGRI, Bethesda, MD 20892 USA. [Abdallah, Assya] George Washington Univ, Sch Med & Hlth Sci, Washington, DC 20037 USA. [Juenger, Christopher R.] US FDA, Rockville, MD 20857 USA. RP Durbin, RM (reprint author), Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Cambridge CB10 1SA, England. RI Cooper, David/H-4384-2011; Xing, Jinchuan/A-2489-2012; Sincan, Murat /A-3794-2010; Alkan, Can/D-2982-2009; Abecasis, Goncalo/B-7840-2010; Chen, Ken/A-1074-2009; Altshuler, David/A-4476-2009; MacArthur, Daniel/E-3275-2010; Browning, Brian/A-1178-2010; Schreiber, Stefan/B-6748-2008; Schaffner, Stephen/D-1189-2011; Ding, Jun/G-3918-2011; Li, Heng/D-9344-2011; De La Vega, Francisco/H-3832-2011; Wang, Jun/B-9503-2016; Casals, Ferran/H-4347-2015; Wang, Jun/C-8434-2016; Lunter, Gerton/H-4939-2016; Pearson, John/F-2249-2011; Mu, Xinmeng/P-2562-2016; Stone, Eric/Q-7840-2016; Mills, Ryan/A-1979-2011; Dahl, Andreas/E-3783-2017; Ye, Kai/B-3640-2012; Cartwright, Reed/A-9707-2009; Wendl, Michael/A-2741-2008; Rosenstiel, Philip/A-5137-2009; Korbel, Jan/G-6470-2012; Kelley, Joanna/H-1693-2012; Dermitzakis, Emmanouil/B-7687-2013; Khurana, Ekta/C-4933-2013; Abyzov, Alexej/M-4284-2013; Le, Quang/A-4861-2012; Myers, Simon/A-6792-2015; Tumian, Afidalina/J-4404-2014; Li, Yingrui/K-1064-2015; Albers, Kees/A-4170-2015 OI Cooper, David/0000-0002-8943-8484; Alkan, Can/0000-0002-5443-0706; Altshuler, David/0000-0002-7250-4107; Browning, Brian/0000-0001-6454-6633; Schreiber, Stefan/0000-0003-2254-7771; Li, Heng/0000-0003-4874-2874; Hinrichs, Angie/0000-0002-1697-1130; Lunter, Gerton/0000-0002-3798-2058; Iqbal, Zamin/0000-0001-8466-7547; Keane, Thomas/0000-0001-7532-6898; Zheng Bradley, Xiangqun/0000-0002-9324-2708; Abyzov, Alexej/0000-0001-5405-6729; Ayub, Qasim/0000-0003-3291-0917; Keenan, Stephen/0000-0002-9141-7690; Sebat, Jonathan/0000-0002-9087-526X; Sudmant, Peter/0000-0002-9573-8248; Kidd, Jeffrey/0000-0002-9631-1465; Radhakrishnan, Rajesh/0000-0001-7170-699X; Sidore, Carlo/0000-0001-7504-7477; Lindsay, Sarah/0000-0002-0965-3070; Abecasis, Goncalo/0000-0003-1509-1825; Herrero, Javier/0000-0001-7313-717X; Clarke, Laura/0000-0002-5989-6898; Yu, Jin/0000-0002-2990-6602; Flicek, Paul/0000-0002-3897-7955; McLaren, William/0000-0001-6218-1116; Walter, Klaudia/0000-0003-4448-0301; Wang, Jun/0000-0002-2113-5874; Leinonen, Rasko/0000-0002-2639-7187; Kulesha, Eugene/0000-0002-4285-6232; Haraksingh, Rajini/0000-0002-6644-8874; Zalunin, Vadim/0000-0002-7722-1958; Kelley, Joanna/0000-0002-7731-605X; Casals, Ferran/0000-0002-8941-0369; Wang, Jun/0000-0002-8540-8931; Pearson, John/0000-0003-0904-4598; Mu, Xinmeng/0000-0002-8079-0828; Mills, Ryan/0000-0003-3425-6998; Dahl, Andreas/0000-0002-2668-8371; Stuetz, Adrian/0000-0001-7650-3470; Cunningham, Fiona/0000-0002-7445-2419; Quinlan, Aaron/0000-0003-1756-0859; Durbin, Richard/0000-0002-9130-1006; Rosenstiel, Philip/0000-0002-9692-8828; Korbel, Jan/0000-0002-2798-3794; Le, Quang/0000-0002-3715-210X; Myers, Simon/0000-0002-2585-9626; Tumian, Afidalina/0000-0003-2763-6677; Albers, Kees/0000-0003-4115-3727 FU Wellcome Trust [WT089088/Z/09/Z, WT085532AIA, WT086084/Z/08/Z, WT081407/Z/06/Z, WT075491/Z/04, WT077009]; Medical Research Council [G0801823]; British Heart Foundation [RG/09/012/28096]; The Leverhulme Trust; EPSRC; Louis-Jeantet Foundation; Swiss National Science Foundation; NGI/EBI [050-72-436]; National Basic Research Program of China (973 program) [2011CB809200]; National Natural Science Foundation of China [30725008, 30890032, 30811130531, 30221004]; Chinese 863 program [2006AA02Z177, 2006AA02Z334, 2006AA02A302, 2009AA022707]; Shenzhen Municipal Government of China [JC200903190767A, JC200903190772A, CXB200903110066A, ZYC200903240077A, ZYC200903240076A, ZYC200903240080A]; Danish Natural Science Research Council; German Research Foundation (Deutsche Forschungsgemeinschaft); BMBF [01GS08201, PREDICT 0315428A]; BMBF NGFN PLUS; EU [242257]; Max Planck Society; Genome Quebec; Ministry of Economic Development, Innovation and Trade [PSR-SIIRI-195]; National Library of Medicine; National Institute of Environmental Health Sciences; NIH [P41HG4221, U01HG5209, P41HG4222, R01GM59290, R01GM72861, R01HG2651, R01MH84698, U01HG5214, P01HG4120, U54HG2750, U54HG2757, U01HG5210, U01HG5208, U01HG5211, R01HG3698, R01HG4719, RC2HG5552, R01HG3229, P50HG2357, R01HG4960, P41HG2371, U41HG4568, R01HG4333]; BWF and Packard Foundation; Pew Charitable Trust; NSF; [S10RR025056] FX We thank many people who contributed to this project: K. Beal, S. Fitzgerald, G. Cochrane, V. Silventoinen, P. Jokinen, E. Birney and J. Ahringer for comments on the manuscript; T. Hunkapiller and Q. Doan for their advice and coordination; N. Kalin, F. Laplace, J. Wilde, S. Paturej, I. Kuhndahl, J. Knight, C. Kodira and M. Boehnke for valuable discussions; Z. Cheng, S. Sajjadian and F. Hormozdiari for assistance in managing data sets; and D. Leja for help with the figures. We thank the Yoruba in Ibadan, Nigeria, the Han Chinese in Beijing, China, the Japanese in Tokyo, Japan, the Utah CEPH community, the Luhya in Webuye, Kenya, the Toscani in Italia, and the Chinese in Denver, Colorado, for contributing samples for research. This research was supported in part by Wellcome Trust grants WT089088/Z/09/Z to R. M. D.; WT085532AIA to P. F.; WT086084/Z/08/Z to G. A. M.; WT081407/Z/06/Z to J. S. K.; WT075491/Z/04 to G. L.; WT077009 to C.T.-S.; Medical Research Council grant G0801823 to J. L. M.; British Heart Foundation grant RG/09/012/28096 to C. A.; The Leverhulme Trust and EPSRC studentships to L. M. and A. T.; the Louis-Jeantet Foundation and Swiss National Science Foundation in support of E. T. D. and S. B. M.; NGI/EBI fellowship 050-72-436 to K.Y.; a National Basic Research Program of China (973 program no. 2011CB809200); the National Natural Science Foundation of China (30725008, 30890032, 30811130531, 30221004); the Chinese 863 program (2006AA02Z177, 2006AA02Z334, 2006AA02A302, 2009AA022707); the Shenzhen Municipal Government of China (grants JC200903190767A, JC200903190772A, ZYC200903240076A, CXB200903110066A, ZYC200903240077A, ZYC200903240076A and ZYC200903240080A); the Ole Romer grant from the Danish Natural Science Research Council; an Emmy Noether Fellowship of the German Research Foundation (Deutsche Forschungsgemeinschaft) to J.O.K.; BMBF grant 01GS08201; BMBF grant PREDICT 0315428A to R. H.; BMBF NGFN PLUS and EU 6th framework READNA to S. S.; EU 7th framework 242257 to A. V. S.; the Max Planck Society; a grant from Genome Quebec and the Ministry of Economic Development, Innovation and Trade, PSR-SIIRI-195 to P. A.; the Intramural Research Program of the NIH; the National Library of Medicine; the National Institute of Environmental Health Sciences; and NIH grants P41HG4221 and U01HG5209 to C. L.; P41HG4222 to J. S.; R01GM59290 to L. B. J. and M. A. B.; R01GM72861 to M. P.; R01HG2651 and R01MH84698 to G. R. A.; U01HG5214 to G. R. A. and A. C.; P01HG4120 to E. E. E.; U54HG2750 to D. L. A.; U54HG2757 to A. C.; U01HG5210 to D. C.; U01HG5208 to M. J. D.; U01HG5211 to R. A. G.; R01HG3698, R01HG4719 and RC2HG5552 to G. T. M.; R01HG3229 to C. D. B. and A. G. C.; P50HG2357 to M. S.; R01HG4960 to B. L. B; P41HG2371 and U41HG4568 to D. H.; R01HG4333 to A. M. L.; U54HG3273 to R. A. G.; U54HG3067 to E. S. L.; U54HG3079 to R. K. W.; N01HG62088 to the Coriell Institute; S10RR025056 to the Translational Genomics Research Institute; Al Williams Professorship funds for M. B. G.; the BWF and Packard Foundation support for P. C. S.; the Pew Charitable Trusts support for G. R. A.; and an NSF Minority Postdoctoral Fellowship in support of R. D. H. E. E. E. is an HHMI investigator, M. P. is an HHMI Early Career Scientist, and D. M. A. is Distinguished Clinical Scholar of the Doris Duke Charitable Foundation. NR 50 TC 3000 Z9 3055 U1 68 U2 580 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD OCT 28 PY 2010 VL 467 IS 7319 BP 1061 EP 1073 DI 10.1038/nature09534 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 671XW UT WOS:000283548600039 ER PT J AU Kwak, EL Bang, YJ Camidge, DR Shaw, AT Solomon, B Maki, RG Ou, SHI Dezube, BJ Janne, PA Costa, DB Varella-Garcia, M Kim, WH Lynch, TJ Fidias, P Stubbs, H Engelman, JA Sequist, LV Tan, WW Gandhi, L Mino-Kenudson, M Wei, GC Shreeve, SM Ratain, MJ Settleman, J Christensen, JG Haber, DA Wilner, K Salgia, R Shapiro, GI Clark, JW Iafrate, AJ AF Kwak, Eunice L. Bang, Yung-Jue Camidge, D. Ross Shaw, Alice T. Solomon, Benjamin Maki, Robert G. Ou, Sai-Hong I. Dezube, Bruce J. Jaenne, Pasi A. Costa, Daniel B. Varella-Garcia, Marileila Kim, Woo-Ho Lynch, Thomas J. Fidias, Panos Stubbs, Hannah Engelman, Jeffrey A. Sequist, Lecia V. Tan, WeiWei Gandhi, Leena Mino-Kenudson, Mari Wei, Greg C. Shreeve, S. Martin Ratain, Mark J. Settleman, Jeffrey Christensen, James G. Haber, Daniel A. Wilner, Keith Salgia, Ravi Shapiro, Geoffrey I. Clark, Jeffrey W. Iafrate, A. John TI Anaplastic Lymphoma Kinase Inhibition in Non-Small-Cell Lung Cancer SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID EML4-ALK FUSION GENE; ACTIVATING MUTATIONS; 2ND-LINE TREATMENT; EGFR MUTATIONS; PHASE-II; GEFITINIB; ALK; IDENTIFICATION; TUMORS; IMMUNOHISTOCHEMISTRY AB BACKGROUND Oncogenic fusion genes consisting of EML4 and anaplastic lymphoma kinase (ALK) are present in a subgroup of non-small-cell lung cancers, representing 2 to 7% of such tumors. We explored the therapeutic efficacy of inhibiting ALK in such tumors in an early-phase clinical trial of crizotinib (PF-02341066), an orally available small-molecule inhibitor of the ALK tyrosine kinase. METHODS After screening tumor samples from approximately 1500 patients with non-small-cell lung cancer for the presence of ALK rearrangements, we identified 82 patients with advanced ALK-positive disease who were eligible for the clinical trial. Most of the patients had received previous treatment. These patients were enrolled in an expanded cohort study instituted after phase 1 dose escalation had established a recommended crizotinib dose of 250 mg twice daily in 28-day cycles. Patients were assessed for adverse events and response to therapy. RESULTS Patients with ALK rearrangements tended to be younger than those without the rearrangements, and most of the patients had little or no exposure to tobacco and had adenocarcinomas. At a mean treatment duration of 6.4 months, the overall response rate was 57% (47 of 82 patients, with 46 confirmed partial responses and 1 confirmed complete response); 27 patients (33%) had stable disease. A total of 63 of 82 patients (77%) were continuing to receive crizotinib at the time of data cutoff, and the estimated probability of 6-month progression-free survival was 72%, with no median for the study reached. The drug resulted in grade 1 or 2 (mild) gastrointestinal side effects. CONCLUSIONS The inhibition of ALK in lung tumors with the ALK rearrangement resulted in tumor shrinkage or stable disease in most patients. C1 [Kwak, Eunice L.; Shaw, Alice T.; Lynch, Thomas J.; Fidias, Panos; Stubbs, Hannah; Engelman, Jeffrey A.; Sequist, Lecia V.; Mino-Kenudson, Mari; Settleman, Jeffrey; Haber, Daniel A.; Clark, Jeffrey W.; Iafrate, A. John] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Dezube, Bruce J.; Costa, Daniel B.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Jaenne, Pasi A.; Gandhi, Leena; Shapiro, Geoffrey I.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Bang, Yung-Jue; Kim, Woo-Ho] Seoul Natl Univ, Coll Med, Seoul, South Korea. [Camidge, D. Ross; Varella-Garcia, Marileila] Univ Colorado, Ctr Canc, Aurora, CO USA. [Solomon, Benjamin] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. [Maki, Robert G.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Ou, Sai-Hong I.] Univ Calif Irvine, Irvine, CA USA. [Tan, WeiWei; Wei, Greg C.; Shreeve, S. Martin; Christensen, James G.; Wilner, Keith] Pfizer Pharmaceut Inc, La Jolla, CA USA. [Ratain, Mark J.; Salgia, Ravi] Univ Chicago, Chicago, IL 60637 USA. RP Kwak, EL (reprint author), Massachusetts Gen Hosp, Ctr Canc, 55 Fruit St,Profess Off Bldg,Rm 238, Boston, MA 02114 USA. EM ekwak@partners.org RI Bang, Yung Jue/J-2759-2012 FU Pfizer; Massachusetts General Hospital (MGH) Cancer Center; Aid for Cancer Research Foundation; National Cancer Institute [CA090578, CA58187, CA46934]; National Institutes of Health [R01CA136851]; American Society of Clinical Oncology (ASCO) Cancer Foundation; NCI-ASCO Cancer Foundation [CA47179, CA06516]; John and Carol Barry Award FX Supported by Pfizer; by grants from the Massachusetts General Hospital (MGH) Cancer Center, the Aid for Cancer Research Foundation, and from an anonymous donor (to MGH); grants from the National Cancer Institute (CA090578, to MGH, Dana-Farber Cancer Institute [DFCI], and Beth Israel Deaconess Medical Center [BIDMC]) and the National Institutes of Health (R01CA136851, to DFCI); a Career Development Award from the American Society of Clinical Oncology (ASCO) Cancer Foundation (to BIDMC); Clinical Investigator Team Leadership Awards from the NCI-ASCO Cancer Foundation (CA47179, to Memorial Sloan-Kettering Cancer Center; and CA06516, to DFCI); a John and Carol Barry Award (to Dr. Kwak); and grants from the National Cancer Institute (CA58187 and CA46934, to the University of Colorado Cancer Center). NR 28 TC 2140 Z9 2237 U1 27 U2 204 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 28 PY 2010 VL 363 IS 18 BP 1693 EP 1703 DI 10.1056/NEJMoa1006448 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 671XF UT WOS:000283546400004 PM 20979469 ER PT J AU Butrynski, JE D'Adamo, DR Hornick, JL Dal Cin, P Antonescu, CR Jhanwar, SC Ladanyi, M Capelletti, M Rodig, SJ Ramaiya, N Kwak, EL Clark, JW Wilner, KD Christensen, JG Janne, PA Maki, RG Demetri, GD Shapiro, GI AF Butrynski, James E. D'Adamo, David R. Hornick, Jason L. Dal Cin, Paola Antonescu, Cristina R. Jhanwar, Suresh C. Ladanyi, Marc Capelletti, Marzia Rodig, Scott J. Ramaiya, Nikhil Kwak, Eunice L. Clark, Jeffrey W. Wilner, Keith D. Christensen, James G. Jaenne, Pasi A. Maki, Robert G. Demetri, George D. Shapiro, Geoffrey I. TI Crizotinib in ALK-Rearranged Inflammatory Myofibroblastic Tumor SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID CELL LUNG-CANCER; ANAPLASTIC LYMPHOMA; KINASE; EXPRESSION; PSEUDOTUMOR; MECHANISMS; INHIBITOR; IMATINIB; THERAPY; FUSION AB Inflammatory myofibroblastic tumor (IMT) is a distinctive mesenchymal neoplasm characterized by a spindle-cell proliferation with an inflammatory infiltrate. Approximately half of IMTs carry rearrangements of the anaplastic lymphoma kinase (ALK) locus on chromosome 2p23, causing aberrant ALK expression. We report a sustained partial response to the ALK inhibitor crizotinib (PF-02341066, Pfizer) in a patient with ALK-translocated IMT, as compared with no observed activity in another patient without the ALK translocation. These results support the dependence of ALK-rearranged tumors on ALK-mediated signaling and suggest a therapeutic strategy for genomically identified patients with the aggressive form of this soft-tissue tumor. C1 [Butrynski, James E.; Demetri, George D.] Dana Farber Harvard Canc Ctr, Ludwig Ctr, Boston, MA 02115 USA. [Butrynski, James E.; Hornick, Jason L.; Capelletti, Marzia; Rodig, Scott J.; Kwak, Eunice L.; Clark, Jeffrey W.; Jaenne, Pasi A.; Demetri, George D.; Shapiro, Geoffrey I.] Harvard Univ, Sch Med, Boston, MA USA. [Hornick, Jason L.; Dal Cin, Paola; Rodig, Scott J.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Kwak, Eunice L.; Clark, Jeffrey W.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [D'Adamo, David R.; Antonescu, Cristina R.; Jhanwar, Suresh C.; Ladanyi, Marc; Maki, Robert G.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Wilner, Keith D.; Christensen, James G.] Pfizer Global Res & Dev, La Jolla, CA USA. [Shapiro, Geoffrey I.] Dana Farber Canc Inst, Early Drug Dev Ctr, Boston, MA 02115 USA. RP Demetri, GD (reprint author), Dana Farber Harvard Canc Ctr, Ludwig Ctr, Dana 1212,44 Binney St, Boston, MA 02115 USA. EM gdemetri@partners.org; geoffrey_shapiro@dfci.harvard.edu FU National Institutes of Health [R01-CA136851, P01-CA47179, RC2-CA148260]; National Cancer Institute-American Society of Clinical Oncology Cancer Foundation; Cycle for Survival FX Supported by Pfizer and by grants from the National Institutes of Health (R01-CA136851, to Dr. Janne; and P01-CA47179 and RC2-CA148260, to Dr. Maki), a Clinical Investigator Team Leadership Supplemental Award from the National Cancer Institute-American Society of Clinical Oncology Cancer Foundation (to Dr. Maki), and a grant from Cycle for Survival (to Dr. Maki). NR 25 TC 281 Z9 300 U1 4 U2 25 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 28 PY 2010 VL 363 IS 18 BP 1727 EP 1733 DI 10.1056/NEJMoa1007056 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 671XF UT WOS:000283546400007 PM 20979472 ER PT J AU Young, LH Bazari, H Durand, ML Branda, JA AF Young, Lucy H. Bazari, Hasan Durand, Marlene L. Branda, John A. TI Case 33-2010: A 22-Year-Old Woman with Blurred Vision and Renal Failure PATHOLOGICAL DIAGNOSES SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID SULFADIAZINE-INDUCED CRYSTALLURIA; TUBULOINTERSTITIAL NEPHRITIS; WEGENERS GRANULOMATOSIS; ENDOPHTHALMITIS; UVEITIS; GLOMERULONEPHRITIS; SARCOIDOSIS C1 [Young, Lucy H.] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. [Bazari, Hasan; Durand, Marlene L.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Branda, John A.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Young, Lucy H.] Harvard Univ, Sch Med, Dept Ophthalmol, Boston, MA USA. [Bazari, Hasan; Durand, Marlene L.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Branda, John A.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Young, LH (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. FU TBS Technologies; DiaSorin FX Dr. Durand reports owning stock in Amgen, Roche, Pfizer, and Novartis; and Dr. Branda reports receiving grant support from TBS Technologies and DiaSorin. No other potential conflict of interest relevant to this article was reported. NR 26 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 OCT 28 PY 2010 VL 363 IS 18 BP 1749 EP 1758 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 671XF UT WOS:000283546400012 PM 20979476 ER PT J AU Mega, JL Simon, T Collet, JP Anderson, JL Antman, EM Bliden, K Cannon, CP Danchin, N Giusti, B Gurbel, P Horne, BD Hulot, JS Kastrati, A Montalescot, G Neumann, FJ Shen, L Sibbing, D Steg, PG Trenk, D Wiviott, SD Sabatine, MS AF Mega, Jessica L. Simon, Tabassome Collet, Jean-Philippe Anderson, Jeffrey L. Antman, Elliott M. Bliden, Kevin Cannon, Christopher P. Danchin, Nicolas Giusti, Betti Gurbel, Paul Horne, Benjamin D. Hulot, Jean-Sebastian Kastrati, Adnan Montalescot, Gilles Neumann, Franz-Josef Shen, Lei Sibbing, Dirk Steg, P. Gabriel Trenk, Dietmar Wiviott, Stephen D. Sabatine, Marc S. TI Reduced-Function CYP2C19 Genotype and Risk of Adverse Clinical Outcomes Among Patients Treated With Clopidogrel Predominantly for PCI A Meta-analysis SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Review ID OF-FUNCTION POLYMORPHISM; PERCUTANEOUS CORONARY INTERVENTION; HEALTHY-SUBJECTS; PLATELET REACTIVITY; STENT THROMBOSIS; CARDIOVASCULAR EVENTS; ANTIPLATELET THERAPY; HEART-ASSOCIATION; ARTERY-DISEASE; TASK-FORCE AB Content Clopidogrel, one of the most commonly prescribed medications, is a prodrug requiring CYP450 biotransformation. Data suggest its pharmacologic effect varies based on CYP2C19 genotype, but there is uncertainty regarding the clinical risk imparted by specific genotypes. Objective To define the risk of major adverse cardiovascular outcomes among carriers of 1 (approximate to 26% prevalence in whites) and carriers of 2 (approximate to 2% prevalence in whites) reduced-function CYP2C19 genetic variants in patients treated with clopidogrel. Data Sources and Study Selection A literature search was conducted (January 2000-August 2010) in MEDLINE, Cochrane Database of Systematic Reviews, and EMBASE. Genetic studies were included in which clopidogrel was initiated in predominantly invasively managed patients in a manner consistent with the current guideline recommendations and in which clinical outcomes were ascertained. Data Extraction Investigators from 9 studies evaluating CYP2C19 genotype and clinical outcomes in patients treated with clopidogrel contributed the relevant hazard ratios (HRs) and 95% confidence intervals (CIs) for specific cardiovascular outcomes by genotype. Results Among 9685 patients (91.3% who underwent percutaneous coronary intervention and 54.5% who had an acute coronary syndrome), 863 experienced the composite end point of cardiovascular death, myocardial infarction, or stroke; and 84 patients had stent thrombosis among the 5894 evaluated for such. Overall, 71.5% were noncarriers, 26.3% had 1 reduced-function CYP2C19 allele, and 2.2% had 2 reduced-function CYP2C19 alleles. A significantly increased risk of the composite end point was evident in both carriers of 1 (HR, 1.55; 95% CI, 1.11-2.17; P=.01) and 2 (HR, 1.76; 95% CI, 1.24-2.50; P=.002) reduced-function CYP2C19 alleles, as compared with noncarriers. Similarly, there was a significantly increased risk of stent thrombosis in both carriers of 1 (HR, 2.67; 95% CI, 1.69-4.22; P<.0001) and 2 (HR, 3.97; 95% CI, 1.75-9.02; P=.001) CYP2C19 reduced-function alleles, as compared with noncarriers. Conclusion Among patients treated with clopidogrel for percutaneous coronary intervention, carriage of even 1 reduced-function CYP2C19 allele appears to be associated with a significantly increased risk of major adverse cardiovascular events, particularly stent thrombosis. JAMA. 2010; 304(16): 1821-1830 C1 [Mega, Jessica L.; Antman, Elliott M.; Cannon, Christopher P.; Wiviott, Stephen D.; Sabatine, Marc S.] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. [Mega, Jessica L.; Antman, Elliott M.; Cannon, Christopher P.; Wiviott, Stephen D.; Sabatine, Marc S.] Harvard Univ, Sch Med, Boston, MA USA. [Simon, Tabassome] AP HP, Dept Pharmacol, Paris, France. [Simon, Tabassome; Collet, Jean-Philippe] Univ Paris 06, Paris, France. [Collet, Jean-Philippe] Grp Hosp Pitie Salpetriere, Inst Cardiol, INSERM, U937, F-75634 Paris, France. [Anderson, Jeffrey L.; Horne, Benjamin D.] Intermt Med Ctr, Cardiovasc Dept, Murray, UT USA. [Bliden, Kevin; Gurbel, Paul] Sinai Hosp, Sinai Ctr Thrombosis Res, Baltimore, MD 21215 USA. [Danchin, Nicolas] Hop Europeen Georges Pompidou, Div Coronary Artery Dis, Paris, France. [Danchin, Nicolas] Univ Paris 05, Paris, France. [Giusti, Betti] Univ Florence, Dept Med & Surg Crit Care, Florence, Italy. [Hulot, Jean-Sebastian] Pitie Salpetriere Univ Hosp, Inst Cardiol, Paris, France. [Hulot, Jean-Sebastian] Pitie Salpetriere Univ Hosp, Dept Pharmacol, Paris, France. [Kastrati, Adnan; Sibbing, Dirk] Deutsch Herzzentrum Munich, Dept Cardiol, Munich, Germany. [Montalescot, Gilles] CHU Pitie Salpetriere, Inst Cardiol, Paris, France. [Shen, Lei] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Steg, P. Gabriel] Univ Paris 07, INSERM, U698, Paris, France. [Steg, P. Gabriel] Hop Bichat Assistance Publ, Paris, France. [Trenk, Dietmar] Herz Zentrum Bad Krozingen, Dept Clin Pharmacol, Bad Krozingen, Germany. RP Mega, JL (reprint author), Brigham & Womens Hosp, Dept Med, Div Cardiovasc, TIMI Study Grp, 350 Longwood Ave,1st Floor, Boston, MA 02115 USA. EM jmega@partners.org; msabatine@partners.org RI Hulot, Jean-Sebastien/A-2278-2016; Giusti, Betti/K-6978-2016 OI Hulot, Jean-Sebastien/0000-0001-5463-6117; Giusti, Betti/0000-0002-8708-9444 FU Bayer Healthcare; Bristol-Myers Squibb; Daiichi Sankyo; Eli Lilly; Johnson Johnson; Sanofi-Aventis; AstraZeneca; Novartis; Servier; Pfizer; Caisse d'Assurance Maladie; Guerbet Medical; Medtronic; Boston Scientific; Cordis; Stago; Centocor; Fondation de France; INSERM; Federation Francaise de Cardiologie; Societe Francaise de Cardiologie; Accumetrics; GlaxoSmithKline; Intekrin Therapeutics; Merck; Takeda; Medicines Company; Schering Plough; Millennium; Bayer; Haemonetics; Biotronik; Medco Research Institute; Medco Health Solutions; Abbott Vascular; ITC Edison; Eisai; Menarini; Portola; Sharpe Dohme; Dynabyte; Astellas; Daiichi Sankyo/Lilly; Otsuka; Roche; Merck-Schering Plough; Arena; National Institutes of Health [K99/R00HL098461-01] FX Dr Mega reports receiving research grant funding from Bayer Healthcare, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly, Johnson & Johnson, and Sanofi-Aventis; research supplies from Accumetrics and Nanosphere; consulting fees from AstraZeneca, Bristol-Myers Squibb, and Sanofi-Aventis; and lecture fees from Novartis. Dr Simon reports receiving research grant funding from Servier, Pfizer, Daiichi Sankyo, Eli Lilly, Sanofi-Aventis, AstraZeneca, and Caisse d'Assurance Maladie; and consulting fees from Eli Lilly, Daiichi Sankyo, Sanofi-Aventis, Bristol-Myers Squibb, and AstraZeneca. Dr Collet reports receiving research grant funding from Bristol-Myers Squibb, Sanofi-Aventis, Eli Lilly, Guerbet Medical, Medtronic, Boston Scientific, Cordis, Stago, Centocor, Fondation de France, INSERM, Federation Francaise de Cardiologie, and Societe Francaise de Cardiologie; lecture fees from Bristol-Myers Squibb, Sanofi-Aventis, and Eli Lilly; and consulting fees from Sanofi-Aventis, Eli Lilly, and Bristol-Myers Squibb. Dr Anderson reports receiving consulting fees from Bristol-Myers Squibb and Sanofi-Aventis. Dr Antman reports receiving research grant funding from Daiichi Sankyo and Eli Lilly; consulting fees from Sanofi-Aventis; and lecture fees from Eli Lilly and Sanofi-Aventis. Dr Cannon reports receiving research grant funding from Accumetrics, AstraZeneca, GlaxoSmithKline, Intekrin Therapeutics, Merck, and Takeda; serving on the advisory board for Bristol-Myers Squibb/Sanofi, Novartis, and Alnylam and donating the funds to charity; and serving as a clinical advisor with equity in Automedics Medical Systems. Dr Danchin reports receiving research grant funding from AstraZeneca, Eli Lilly, Merck, Novartis, Pfizer, Sanofi-Aventis, Servier, and The Medicines Company; lecture fees from AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, GlaxoSmithKline, Menarini, Merck-Serono, MSD-Schering Plough, Servier, and Sanofi-Aventis; and consulting fees from AstraZeneca, Eli Lilly, Novo, Sanofi-Aventis, and Servier. Dr Gurbel reports receiving research grant funding from Schering Plough, Millennium, AstraZeneca, Bayer, Haemonetics, Medtronic, and Boston Scientific; and honoraria from Schering Plough, AstraZeneca, Bayer, Portola, and Medtronic. Dr Hulot reports receiving research grant support from Fondation de France, INSERM, Federation Francaise de Cardiologie, Biotronik, and Medco Research Institute; consulting fees from Biotronik and Medco Health Solutions; and lecture fees from Sanofi-Aventis, Daiichi Sankyo, Eli Lilly, and Bristol-Myers Squibb. Dr Montalescot reports receiving research grant funding from Abbott Vascular, Bristol-Myers Squibb, Boston Scientific, Centocor, Cordis, Eli Lilly, Federation Francaise de Cardiologie, Fondation de France, Guerbet Medical, INSERM, ITC Edison, Medtronic, Pfizer, Sanofi-Aventis, Societe Francaise de Cardiologie, and Stago; consulting fees from AstraZeneca, Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, Daiichi-Sankyo, Eisai, Eli Lilly, Menarini, Novartis, Pfizer, Portola, Sanofi-Aventis Group, Schering-Plough, and The Medicines Company; and lecture fees from Abbott Vascular, Accumetrics, AstraZeneca, Bristol-Myers Squibb, Cordis, Daiichi-Sankyo, Eli Lilly, GlaxoSmithKline, Menarini, Merck Sharpe & Dohme, Pfizer, Sanofi-Aventis, and Schering-Plough. Dr Shen reports being employed and having ownership interest in Eli Lilly. Dr Sibbing reports receiving consulting fees from Eli Lilly and lecture fees from Dynabyte and The Medicines Company.; Dr Steg reports receiving research grant funding from Servier; consultingfees from Astellas, AstraZeneca, Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo/Lilly, GlaxoSmithKline, Medtronic, Merck, Otsuka, Pfizer, Roche, Sanofi-Aventis, Servier, and The Medicines Company; and is a stockholder in Aterovax. Dr Trenk reports receiving research grant support from Eli Lilly; consulting fees from Eli Lilly, Daiichi Sankyo, and AstraZeneca; and lecture fees from Eli Lilly and Daiichi Sankyo. Dr Wiviott reports receiving research grant funding from Eli Lilly, Daiichi Sankyo, and Merck-Schering Plough; honoraria from AstraZeneca, Novartis; Eli Lilly, and Daiichi Sankyo; and consulting fees from AstraZeneca, Sanofi-Aventis, Portola, and Arena. Dr Sabatine reports receiving research grant funding from AstraZeneca, Bristol-Myers Squibb, Daiichi Sankyo, Schering Plough (now Merck), and Sanofi-Aventis; honoraria from Bristol-Myers Squibb, Sanofi-Aventis, and Eli Lilly; and consulting fees from AstraZeneca, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly, and Sanofi-Aventis. The other authors reported no disclosures.; Dr Mega is supported in part by grant K99/R00HL098461-01 from the National Institutes of Health. NR 53 TC 463 Z9 496 U1 10 U2 47 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD OCT 27 PY 2010 VL 304 IS 16 BP 1821 EP 1830 DI 10.1001/jama.2010.1543 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 671JZ UT WOS:000283501300023 PM 20978260 ER PT J AU Fujimoto, K Araki, K McCarthy, DM Sims, JR Ren, JQ Zhang, X Bhide, PG AF Fujimoto, K. Araki, K. McCarthy, D. M. Sims, J. R. Ren, J. Q. Zhang, X. Bhide, P. G. TI A TRANSGENIC MOUSE MODEL OF NEUROEPITHELIAL CELL SPECIFIC INDUCIBLE OVEREXPRESSION OF DOPAMINE D1-RECEPTOR SO NEUROSCIENCE LA English DT Article DE ganglionic eminence; striatum; cerebral cortex; D1-receptor; neurogenesis; nestin ID PRENATAL COCAINE EXPOSURE; D-3 RECEPTOR STIMULATION; CORTICAL PRECURSOR CELLS; GABA NEURON MIGRATION; CEREBRAL-CORTEX; POSTNATAL-DEVELOPMENT; GENE-EXPRESSION; CORPUS STRIATUM; GANGLIONIC EMINENCE; MESSENGER-RNAS AB Dopamine and its receptors appear in the brain during early embryonic period suggesting a role for dopamine in brain development. In fact, dopamine receptor imbalance resulting from impaired physiological balance between D1- and D2-receptor activities can perturb brain development and lead to persisting changes in brain structure and function. Dopamine receptor imbalance can be produced experimentally using pharmacological or genetic methods. Pharmacological methods tend to activate or antagonize the receptors in all cell types. In the traditional gene knockout models the receptor imbalance occurs during development and also at maturity. Therefore, assaying the effects of dopamine imbalance on specific cell types (e.g. precursor versus postmitotic cells) or at specific periods of brain development (e.g. pre- or postnatal periods) is not feasible in these models. We describe a novel transgenic mouse model based on the tetracycline dependent inducible gene expression system in which dopamine D1-receptor transgene expression is induced selectively in neuroepithelial cells of the embryonic brain at experimenter-chosen intervals of brain development. In this model, doxycycline-induced expression of the transgene causes significant overexpression of the D1-receptor and significant reductions in the incorporation of the S-phase marker bromodeoxyuridine into neuroepithelial cells of the basal and dorsal telencephalon indicating marked effects on telencephalic neurogenesis. The D1-receptor overexpression occurs at higher levels in the medial ganglionic eminence (MGE) than the lateral ganglionic eminence (LGE) or cerebral wall (CW). Moreover, although the transgene is induced selectively in the neuroepithelium, D1-receptor protein overexpression appears to persist in postmitotic cells. The mouse model can be modified for neuroepithelial cell-specific inducible expression of other transgenes or induction of the D1-receptor transgene in other cells in specific brain regions by crossbreeding the mice with transgenic mouse lines available already. (C) 2010 IBRO. Published by Elsevier Ltd. All rights reserved. C1 [Fujimoto, K.; Araki, K.; McCarthy, D. M.; Sims, J. R.; Zhang, X.; Bhide, P. G.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02129 USA. [Sims, J. R.; Ren, J. Q.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02129 USA. RP Bhide, PG (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02129 USA. EM Bhide@helix.mgh.harvard.edu OI Bhide, Pradeep/0000-0003-4236-9415 FU USPHS [RO1DA020796, P30NS045776, K08NS049241] FX Acknowledgments Supported by USPHS grants RO1DA020796 and P30NS045776 (PGB) and K08NS049241 (JRS). We are grateful to Drs. Steven A. Reeves, Ph.D. (Massachusetts General Hospital, Boston) and Yoko Aoki, Ph.D. (Tohoku University, Sendai, Japan) for reagents and advice. We gratefully acknowledge technical assistance by Igor Bagayev and Enric Navas Peres. NR 58 TC 0 Z9 0 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PD OCT 27 PY 2010 VL 170 IS 3 BP 961 EP 970 DI 10.1016/j.neuroscience.2010.07.036 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 675KZ UT WOS:000283830900029 PM 20674683 ER PT J AU Dey, BR Chung, SS Spitzer, TR Zheng, H MacGillivray, TE Seldin, DC McAfee, S Ballen, K Attar, E Wang, T Shin, J Newton-Cheh, C Moore, S Sanchorawala, V Skinner, M Madsen, JC Semigran, MJ AF Dey, Bimalangshu R. Chung, Stephen S. Spitzer, Thomas R. Zheng, Hui MacGillivray, Thomas E. Seldin, David C. McAfee, Steven Ballen, Karen Attar, Eyal Wang, Thomas Shin, Jordan Newton-Cheh, Christopher Moore, Stephanie Sanchorawala, Vaishali Skinner, Martha Madsen, Joren C. Semigran, Marc J. TI Cardiac Transplantation Followed by Dose-Intensive Melphalan and Autologous Stem-Cell Transplantation for Light Chain Amyloidosis and Heart Failure SO TRANSPLANTATION LA English DT Article DE Amyloid; Cardiac amyloidosis; Stem-cell transplantation ID PRIMARY SYSTEMIC AMYLOIDOSIS; AL AMYLOIDOSIS; RANDOMIZED-TRIAL; PREDNISONE; SURVIVAL; DISEASE; CARDIOMYOPATHY; COLCHICINE; FEATURES AB Background. Patients with light chain (AL) amyloidosis who present with severe heart failure due to cardiac involvement rarely survive more than 6 months. Survival after cardiac transplantation is markedly reduced due to the progression of amyloidosis. Autologous stem-cell transplantation (ASCT) has become a common therapy for AL amyloidosis, but there is an exceedingly high treatment-related mortality in patients with heart failure. Methods. We developed a treatment strategy of cardiac transplant followed by ASCT. Twenty-six patients were evaluated, and of 18 eligible patients, nine patients underwent cardiac transplantation. Eight of these patients subsequently received an ASCT. Results. Six of seven evaluable patients achieved a complete hematologic remission, and one achieved a partial remission. At a median follow-up of 56 months from cardiac transplant, five of seven patients are alive without recurrent amyloidosis. Their survival is comparable with 17,389 patients who received heart transplants for nonamyloid heart disease: 64% in nonamyloid vs. 60% in amyloid patients at 7 years (P=0.83). Seven of eight transplanted patients have had no evidence of amyloid in their cardiac allograft. Conclusions. This demonstrates that cardiac transplantation followed by ASCT is feasible in selected patients with AL amyloidosis and heart failure, and that such a strategy may lead to improved overall survival. C1 [Zheng, Hui; Semigran, Marc J.] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Seldin, David C.; Sanchorawala, Vaishali; Skinner, Martha] Boston Univ, Sch Med, Dept Med, Stem Cell Transplantat Program, Boston, MA 02118 USA. [Seldin, David C.; Sanchorawala, Vaishali; Skinner, Martha] Boston Univ, Sch Med, Dept Med, Amyloid Treatment & Res Program, Boston, MA 02118 USA. [Seldin, David C.; Sanchorawala, Vaishali; Skinner, Martha] Boston Med Ctr, Boston, MA USA. RP Semigran, MJ (reprint author), Massachusetts Gen Hosp, Ctr Biostat, Bigelow 800, Boston, MA 02114 USA. EM msemigran@partners.org RI Max, Mad/E-5238-2010; OI Max, Mad/0000-0001-6966-6829; Sanchorawala, Vaishali/0000-0002-6307-2445 FU National Institutes of Health [P01 HL68705]; Gerry Foundation; Boston University FX Amyloid research at Boston University School of Medicine/Boston Medical Center was supported by grants from the National Institutes of Health (P01 HL68705), the Gerry Foundation, and the Amyloid Research Fund at Boston University. NR 20 TC 49 Z9 52 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD OCT 27 PY 2010 VL 90 IS 8 BP 905 EP 911 DI 10.1097/TP.0b013e3181f10edb PG 7 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 668JD UT WOS:000283263700016 PM 20733534 ER PT J AU Velagaleti, RS Gona, P Larson, MG Wang, TJ Levy, D Benjamin, EJ Selhub, J Jacques, PF Meigs, JB Tofler, GH Vasan, RS AF Velagaleti, Raghava S. Gona, Philimon Larson, Martin G. Wang, Thomas J. Levy, Daniel Benjamin, Emelia J. Selhub, Jacob Jacques, Paul F. Meigs, James B. Tofler, Geoffrey H. Vasan, Ramachandran S. TI Multimarker Approach for the Prediction of Heart Failure Incidence in the Community SO CIRCULATION LA English DT Article DE biomarkers; epidemiology; heart failure; natriuretic peptides; risk; prediction ID C-REACTIVE PROTEIN; PLASMA NATRIURETIC PEPTIDE; PLASMINOGEN-ACTIVATOR INHIBITOR-1; PRIOR MYOCARDIAL-INFARCTION; METABOLIC RISK-FACTORS; CARDIOVASCULAR EVENTS; DIABETES-MELLITUS; BLOOD-PRESSURE; DIASTOLIC DYSFUNCTION; HOMOCYSTEINE LEVELS AB Background-Several biological pathways are activated in ventricular remodeling and in overt heart failure (HF). There are no data, however, on the incremental utility of a parsimonious set of biomarkers (reflecting pathways implicated in HF) for predicting HF risk in the community. Methods and Results-We related a multibiomarker panel to the incidence of a first HF event in 2754 Framingham Heart Study participants (mean age, 58 years; 54% women) who were free of HF and underwent routine assays for 6 biomarkers (C-reactive protein, plasminogen activator inhibitor-1, homocysteine, aldosterone-to-renin ratio, B-type natriuretic peptide, and urinary albumin-to-creatinine ratio). We estimated model c statistic, calibration, and net reclassification improvement to assess the incremental predictive usefulness of biomarkers. We also related biomarkers to the incidence of nonischemic HF in participants without prevalent coronary heart disease. On follow-up (mean, 9.4 years), 95 first HF events occurred (54 in men). In multivariable-adjusted models, the biomarker panel was significantly related to HF risk (P=0.00005). On backward elimination, B-type natriuretic peptide and urinary albumin-to-creatinine ratio emerged as key biomarkers predicting HF risk; hazards ratios per 1-SD increment in log marker were 1.52 (95% confidence interval, 1.24 to 1.87) and 1.35 (95% confidence interval, 1.11 to 1.66), respectively. B-type natriuretic peptide and urinary albumin-to-creatinine ratio significantly improved the model c statistic from 0.84 (95% confidence interval, 0.80 to 0.88) in standard models to 0.86 (95% confidence interval, 0.83 to 0.90), enhanced risk reclassification (net reclassification improvement=0.13; P=0.002), and were independently associated with nonischemic HF risk. Conclusion-Using a multimarker strategy, we identified B-type natriuretic peptide and urinary albumin-to-creatinine ratio as key risk factors for new-onset HF with incremental predictive utility over standard risk factors. (Circulation. 2010;122:1700-1706.) C1 [Velagaleti, Raghava S.; Gona, Philimon; Larson, Martin G.; Wang, Thomas J.; Levy, Daniel; Benjamin, Emelia J.; Meigs, James B.; Vasan, Ramachandran S.] Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA. [Gona, Philimon; Larson, Martin G.] Boston Univ, Sch Med, Dept Math & Stat, Boston, MA 02118 USA. [Gona, Philimon; Larson, Martin G.] Boston Univ, Sch Med, Prevent Med & Cardiol Sect, Boston, MA 02118 USA. [Benjamin, Emelia J.; Vasan, Ramachandran S.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. [Wang, Thomas J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Levy, Daniel] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA. [Selhub, Jacob; Jacques, Paul F.] Tufts Univ, Jean Mayer US Dept Agr, Human Nutr Res Ctr Aging, Boston, MA 02111 USA. [Meigs, James B.] Massachusetts Gen Hosp, Dept Med, Div Gen Med, Boston, MA 02114 USA. [Meigs, James B.] Harvard Univ, Sch Med, Boston, MA USA. [Tofler, Geoffrey H.] Royal N Shore Hosp, Dept Cardiol, Sydney, NSW, Australia. RP Vasan, RS (reprint author), Framingham Heart Dis Epidemiol Study, 73 Mt Wayte Ave, Framingham, MA 01702 USA. EM vasan@bu.edu RI Max, Mad/E-5238-2010; OI Max, Mad/0000-0001-6966-6829; Larson, Martin/0000-0002-9631-1254; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU National Heart, Lung and Blood Institute [N01-HC-25195]; National Institutes of Health [RO1HL67288, HL080124, K24-HL04334]; American Diabetes Association; National Institute of Diabetes and Digestive and Kidney Diseases [K24DK080140] FX This work was supported by the National Heart, Lung and Blood Institute (contract N01-HC-25195); National Institutes of Health grants RO1HL67288, HL080124, and K24-HL04334 (Dr Vasan); and an American Diabetes Association clinical research grant. Dr Meigs is supported by National Institute of Diabetes and Digestive and Kidney Diseases K24DK080140. NR 55 TC 56 Z9 57 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2010 VL 122 IS 17 BP 1700 EP + DI 10.1161/CIRCULATIONAHA.109.929661 PG 19 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 670PU UT WOS:000283440600014 PM 20937976 ER PT J AU Morishige, K Kacher, DF Libby, P Josephson, L Ganz, P Weissleder, R Aikawa, M AF Morishige, Kunio Kacher, Daniel F. Libby, Peter Josephson, Lee Ganz, Peter Weissleder, Ralph Aikawa, Masanori TI High-Resolution Magnetic Resonance Imaging Enhanced With Superparamagnetic Nanoparticles Measures Macrophage Burden in Atherosclerosis SO CIRCULATION LA English DT Article DE atherosclerosis; inflammation; macrophages; magnetic resonance imaging; nanoparticles ID IRON-OXIDE NANOPARTICLES; IN-VIVO; HYPERLIPIDEMIC RABBITS; OXIDATIVE STRESS; STATIN THERAPY; PLAQUE; MRI; INFLAMMATION; MECHANISMS; CONTRAST AB Background-Macrophages contribute to the progression and acute complications of atherosclerosis. Macrophage imaging may serve as a biomarker to identify subclinical inflamed lesions, to predict future risk, and to aid in the assessment of novel therapies. Methods and Results-To test the hypothesis that nanoparticle-enhanced, high-resolution magnetic resonance imaging (MRI) can measure plaque macrophage accumulation, we used 3-T MRI with a macrophage-targeted superparamagnetic nanoparticle preparation (monocrystalline iron oxide nanoparticles-47 [MION-47]) in cholesterol-fed New Zealand White rabbits 6 months after balloon injury. In vivo MRI visualized thickened abdominal aortas on both T1- and T2-weighted spin-echo images (T1 spin echo, 20 axial slices per animal; T2 spin echo, 28 slices per animal). Seventy-two hours after MION-47 injection, aortas exhibited lower T2 signal intensity compared with before contrast imaging (signal intensity ratio, aortic wall/muscle: before, 1.44 +/- 0.26 versus after, 0.95 +/- 0.22; 164 slices; P<0.01), whereas T1 spin echo images showed no significant change. MRI on ex vivo specimens provided similar results. Histological studies colocalized iron accumulation with immunoreactive macrophages in atheromata. The magnitude of signal intensity reduction on T2 spin echo in vivo images further correlated with macrophage areas in situ (150 slices; r=0.73). Treatment with rosuvastatin for 3 months yielded diminished macrophage content (P<0.05) and reversed T2 signal intensity changes (P<0.005). Signal changes in rosuvastatin-treated rabbits correlated with reduced macrophage burden (r=0.73). In vitro validation studies showed concentration-dependent MION-47 uptake by human primary macrophages. Conclusion-The magnitude of T2 signal intensity reduction in high-resolution MRI after administration of superparamagnetic phagocytosable nanoparticles can assess macrophage burden in atheromata, providing a clinically translatable tool to identify inflamed plaques and to monitor therapy-mediated changes in plaque inflammation. (Circulation. 2010;122:1707-1715.) C1 [Aikawa, Masanori] Harvard Univ, Brigham & Womens Hosp, Sch Med,Dept Med, Ctr Excellence Vasc Biol,Cardiovasc Div, Boston, MA 02115 USA. [Kacher, Daniel F.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Morishige, Kunio; Kacher, Daniel F.; Libby, Peter; Weissleder, Ralph; Aikawa, Masanori] Harvard Univ, Sch Med, Donald W Reynolds Cardiovasc Clin Res Ctr, Boston, MA 02115 USA. [Josephson, Lee; Weissleder, Ralph] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA USA. RP Aikawa, M (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med,Dept Med, Ctr Excellence Vasc Biol,Cardiovasc Div, 77 Ave Louis Pasteur, Boston, MA 02115 USA. EM maikawa@rics.bwh.harvard.edu FU Reynolds Foundation; National Institutes of Health [HL56895, HL66086, HL80472, HL078641, U01-HL080731, U41RR19703]; AstraZeneca; Japan Heart Foundation/Bayer; Uehara Memorial Foundation FX This work was supported in part by grants from the Reynolds Foundation (Drs Libby and Weissleder), the National Institutes of Health (HL56895 to Drs Libby, Aikawa, and Ganz; HL66086 to Dr Aikawa; HL80472 to Dr Libby; HL078641 to Dr Weissleder; TPEN grant U01-HL080731 to Drs Weissleder and Libby; U41RR19703 to D. F. Kacher), the AstraZeneca Investigator-Sponsored Study Program (Dr Aikawa), the Japan Heart Foundation/Bayer (Dr Morishige), and the Uehara Memorial Foundation (Dr Morishige). NR 51 TC 82 Z9 86 U1 2 U2 21 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2010 VL 122 IS 17 BP 1707 EP 1715 DI 10.1161/CIRCULATIONAHA.109.891804 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 670PU UT WOS:000283440600015 PM 20937980 ER PT J AU Shah, RV Desai, NR O'Gara, PT AF Shah, Ravi V. Desai, Nihar R. O'Gara, Patrick T. TI Asymptomatic Severe Aortic Stenosis Silence of the Lambs? SO CIRCULATION LA English DT Article ID VALVULAR HEART-DISEASE; PREDICTORS AB A 62-year-old man with a past medical history presents to the cardiology clinic for evaluation after a routine echocardiogram obtained for evaluation of palpitations. His clinical history is remarkable for infrequent self-terminating episodes of regular rapid heartbeat over the last 2 months. The events are not associated with chest discomfort, dyspnea, lightheadedness, dizziness, or flushing. He denies any symptoms of rest or exertional chest discomfort or dyspnea, recent syncope or presyncopal sensations, or paroxysmal nocturnal dyspnea. He states that he has been reducing his physical activity over the last several years because of fatigue. His past medical history is remarkable for hyperlipidemia and erectile dysfunction. He has no drug allergies. His medications include a multivitamin, simvastatin, and tadalafil. He smokes 1 pack of cigarettes per day and has a >30 pack-year smoking history. He neither drinks alcohol nor uses illicit drugs. He is a retired store clerk. C1 [Desai, Nihar R.; O'Gara, Patrick T.] Harvard Univ, Div Cardiovasc Med, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. [Shah, Ravi V.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiol,Dept Med, Boston, MA 02115 USA. RP O'Gara, PT (reprint author), Harvard Univ, Div Cardiovasc Med, Sch Med, Brigham & Womens Hosp, 75 Francis St, Boston, MA 02115 USA. EM rvshah@partners.org; pogara@partners.org NR 10 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 26 PY 2010 VL 122 IS 17 BP 1734 EP 1739 DI 10.1161/CIRCULATIONAHA.110.989152 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 670PU UT WOS:000283440600018 PM 20975009 ER PT J AU Storey, RF Angiolillo, DJ Patil, SB Desai, B Ecob, R Husted, S Emanuelsson, H Cannon, CP Becker, RC Wallentin, L AF Storey, Robert F. Angiolillo, Dominick J. Patil, Shankar B. Desai, Bhaloo Ecob, Rosemary Husted, Steen Emanuelsson, Hakan Cannon, Christopher P. Becker, Richard C. Wallentin, Lars TI Inhibitory Effects of Ticagrelor Compared With Clopidogrel on Platelet Function in Patients With Acute Coronary Syndromes The PLATO (PLATelet inhibition and patient Outcomes) PLATELET Substudy SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE clopidogrel; coronary artery disease; P2Y(12) receptor; platelet; platelet inhibitor ID EVENTS AB Objectives The PLATO (PLATelet inhibition and patient Outcomes) PLATELET substudy aimed to compare the antiplatelet effects of clopidogrel and ticagrelor in patients with acute coronary syndromes. Background The PLATO study demonstrated superiority of ticagrelor over clopidogrel in the prevention of ischemic events in patients with acute coronary syndromes. Methods Patients were randomized to receive either clopidogrel (300- to 600-mg loading dose [LD], 75 mg/day) or ticagrelor (180-mg LD, 90 mg twice daily). The effects of maintenance therapy were studied in 69 patients pre- and 2 to 4 h post-dose after at least 28 days. The LD effect was studied in 24 clopidogrel-naive patients. Light transmittance aggregometry (adenosine diphosphate 5 to 20 mu M), VerifyNow P2Y12, and VASP phosphorylation assays were performed. Results During maintenance therapy, ticagrelor achieved greater suppression of platelet reactivity compared with clopidogrel. The mean maximum light transmittance aggregometry responses (adenosine diphosphate 20 mu M) post-maintenance dose were 44 +/- 15% for clopidogrel and 28 +/- 10% for ticagrelor (p < 0.001). High platelet reactivity was seen more frequently in the clopidogrel group. Proton pump inhibitor use was associated with higher platelet reactivity with clopidogrel but not ticagrelor. The ticagrelor LD also achieved greater inhibition of platelet aggregation compared with the clopidogrel LD. Conclusions Ticagrelor achieves greater antiplatelet effect than clopidogrel in patients with acute coronary syndromes, both in the first hours of treatment and during maintenance therapy. (J Am Coll Cardiol 2010;56:1456-62) (C) 2010 by the American College of Cardiology Foundation C1 [Storey, Robert F.; Patil, Shankar B.; Ecob, Rosemary] Univ Sheffield, Dept Cardiovasc Sci, Sheffield S10 2RX, S Yorkshire, England. [Storey, Robert F.; Patil, Shankar B.; Ecob, Rosemary] NIHR Cardiovasc Biomed Res Unit, Sheffield, S Yorkshire, England. [Angiolillo, Dominick J.; Desai, Bhaloo] Univ Florida, Coll Med Jacksonville, Jacksonville, FL USA. [Husted, Steen] Arhus Univ Hosp, Aarhus, Denmark. [Emanuelsson, Hakan] AstraZeneca, Molndal, Sweden. [Cannon, Christopher P.] Brigham & Womens Hosp, TIMI Study Grp, Boston, MA 02115 USA. [Becker, Richard C.] Duke Clin Res Inst, Durham, NC USA. [Wallentin, Lars] Uppsala Univ, Uppsala Clin Res Ctr, Uppsala, Sweden. [Wallentin, Lars] Uppsala Univ, Dept Med Sci Cardiol, Uppsala, Sweden. RP Storey, RF (reprint author), Univ Sheffield, Dept Cardiovasc Sci, Beech Hill Rd, Sheffield S10 2RX, S Yorkshire, England. EM r.f.storey@sheffield.ac.uk FU AstraZeneca; Daiichi-Sankyo/Eli Lilly; Schering-Plough; Novartis; Teva; Brisol-Myers Squibb/Sanofi; Medicines Co.; Dynabyte; Bristol-Myers Squibb; Sanofi-Aventis; Eli Lilly Co.; Daiichi Sankyo Inc.; GlaxoSmithKline; Otsuka; Portola; Accumetrics; Eisai; Johnson Johnson; Bristol-Myers Squibb/Sanofi; Intekrin Therapeutics; Merck; Takeda; Scientific advisory board of AstraZeneca; Boehringer-Ingelheim; Lilly FX This work was supported by grants to the University of Sheffield and University of Florida from AstraZeneca. Dr. Storey has received consultancy, honoraria, and/or institutional research grants from AstraZeneca, Daiichi-Sankyo/Eli Lilly, Schering-Plough, Novartis, Teva, Brisol-Myers Squibb/Sanofi, The Medicines Co., and Dynabyte. Dr. Angiolillo has received honoraria/lecture fees from Bristol-Myers Squibb, Sanofi-Aventis, Eli Lilly Co., and Daiichi Sankyo Inc.; received honoraria/served on the advisory board for Bristol-Myers Squibb, Sanofi-Aventis, Eli Lilly Co., Daiichi Sankyo Inc., The Medicines Co., Portola, Novartis, Medicure, Accumetrics, Arena Pharmaceuticals, AstraZeneca, and Evolva; and received research grants from GlaxoSmithKline, Otsuka, Eli Lilly Co., Daiichi-Sankyo Inc., The Medicines Co., Portola, Accumetrics, Schering-Plough, AstraZeneca, Eisai, and Johnson & Johnson. Dr. Emanuelsson is an AstraZeneca employee. Dr. Cannon has received research grant/support from Accumetrics, AstraZeneca, Bristol-Myers Squibb/Sanofi Partnership, GlaxoSmithKline, Intekrin Therapeutics, Merck, Novartis, and Takeda; is on the advisory board of Bristol-Myers Squibb/Sanofi Partnership; and is a clinical advisor with equity in Automedics Medical Systems. Dr. Becker has received research support from and is on the scientific advisory board of AstraZeneca. Dr. Wallentin has received institutional grants from AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Schering-Plough, Lilly, and GlaxoSmithKline. All other authors have reported that they have no relationships to disclose. NR 8 TC 158 Z9 170 U1 1 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD OCT 26 PY 2010 VL 56 IS 18 BP 1456 EP 1462 DI 10.1016/j.jacc.2010.03.100 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 665VZ UT WOS:000283065300004 PM 20832963 ER PT J AU Samara, C Rohde, CB Gilleland, CL Norton, S Haggarty, SJ Yanik, MF AF Samara, Chrysanthi Rohde, Christopher B. Gilleland, Cody L. Norton, Stephanie Haggarty, Stephen J. Yanik, Mehmet Fatih TI Large-scale in vivo femtosecond laser neurosurgery screen reveals small-molecule enhancer of regeneration SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE C. elegans; chemical screen; microfluidics ID PROTEIN-KINASE-C; PROGRAMMED CELL-DEATH; NERVE GROWTH-FACTOR; CAENORHABDITIS-ELEGANS; AXON REGENERATION; ON-CHIP; NEURITE OUTGROWTH; SENSORY NEURONS; CYCLIC-AMP; STAUROSPORINE AB Discovery of molecular mechanisms and chemical compounds that enhance neuronal regeneration can lead to development of therapeutics to combat nervous system injuries and neurodegenerative diseases. By combining high-throughput microfluidics and femtosecond laser microsurgery, we demonstrate for the first time large-scale in vivo screens for identification of compounds that affect neurite regeneration. We performed thousands of microsurgeries at single-axon precision in the nematode Caenorhabditis elegans at a rate of 20 seconds per animal. Following surgeries, we exposed the animals to a hand-curated library of approximately one hundred small molecules and identified chemicals that significantly alter neurite regeneration. In particular, we found that the PKC kinase inhibitor staurosporine strongly modulates regeneration in a concentration- and neuronal type-specific manner. Two structurally unrelated PKC inhibitors produce similar effects. We further show that regeneration is significantly enhanced by the PKC activator prostratin. C1 [Samara, Chrysanthi; Rohde, Christopher B.; Gilleland, Cody L.; Yanik, Mehmet Fatih] MIT, Dept Elect Engn & Comp Sci, Cambridge, MA 02139 USA. [Norton, Stephanie; Haggarty, Stephen J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA 02142 USA. RP Yanik, MF (reprint author), MIT, Dept Elect Engn & Comp Sci, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM yanik@mit.edu OI Haggarty, Stephen J./0000-0002-7872-168X FU National Institutes of Health [1-DP2-OD002989]; Packard Fellowship in Science and Engineering; Alfred Sloan Award in Neuroscience; National Science Foundation; Merck FX We thank Robert Horvitz's laboratory for discussions and technical support, Charles Jennings and Matthew Angel for valuable comments, and the C. elegans Genetics Center for the strains. This work was supported by the National Institutes of Health Director's New Innovator Award Program (1-DP2-OD002989), Packard Fellowship in Science and Engineering, Alfred Sloan Award in Neuroscience, National Science Foundation Graduate Fellowship, and Merck Graduate Fellowship. NR 50 TC 65 Z9 68 U1 0 U2 18 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 26 PY 2010 VL 107 IS 43 BP 18342 EP 18347 DI 10.1073/pnas.1005372107 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 673QG UT WOS:000283677400024 PM 20937901 ER PT J AU Stott, SL Hsu, CH Tsukrov, DI Yu, M Miyamoto, DT Waltman, BA Rothenberg, SM Shah, AM Smas, ME Korir, GK Floyd, FP Gilman, AJ Lord, JB Winokur, D Springer, S Irimia, D Nagrath, S Sequist, LV Lee, RJ Isselbacher, KJ Maheswaran, S Haber, DA Toner, M AF Stott, Shannon L. Hsu, Chia-Hsien Tsukrov, Dina I. Yu, Min Miyamoto, David T. Waltman, Belinda A. Rothenberg, S. Michael Shah, Ajay M. Smas, Malgorzata E. Korir, George K. Floyd, Frederick P., Jr. Gilman, Anna J. Lord, Jenna B. Winokur, Daniel Springer, Simeon Irimia, Daniel Nagrath, Sunitha Sequist, Lecia V. Lee, Richard J. Isselbacher, Kurt J. Maheswaran, Shyamala Haber, Daniel A. Toner, Mehmet TI Isolation of circulating tumor cells using a microvortex-generating herringbone-chip SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE microfluidics; ctcs; prostate cancer; clusters; point-of-care ID RESISTANT PROSTATE-CANCER; CARCINOMA-CELLS; PREDICT SURVIVAL; EPITHELIAL-CELLS; BLOOD; ENUMERATION; METASTASIS; DEVICE; SIZE AB Rare circulating tumor cells (CTCs) present in the bloodstream of patients with cancer provide a potentially accessible source for detection, characterization, and monitoring of nonhematological cancers. We previously demonstrated the effectiveness of a microfluidic device, the CTC-Chip, in capturing these epithelial cell adhesion molecule (EpCAM)-expressing cells using antibody-coated microposts. Here, we describe a high-throughput microfluidic mixing device, the herringbone-chip, or "HB-Chip," which provides an enhanced platform for CTC isolation. The HB-Chip design applies passive mixing of blood cells through the generation of microvortices to significantly increase the number of interactions between target CTCs and the antibody-coated chip surface. Efficient cell capture was validated using defined numbers of cancer cells spiked into control blood, and clinical utility was demonstrated in specimens from patients with prostate cancer. CTCs were detected in 14 of 15 (93%) patients with metastatic disease (median 63 CTCs/mL, mean = 386 +/- 238 CTCs/mL), and the tumor-specific TMPRSS2-ERG translocation was readily identified following RNA isolation and RT-PCR analysis. The use of transparent materials allowed for imaging of the captured CTCs using standard clinical histopathological stains, in addition to immunofluorescence-conjugated antibodies. In a subset of patient samples, the low shear design of the HB-Chip revealed microclusters of CTCs, previously unappreciated tumor cell aggregates that may contribute to the hematogenous dissemination of cancer. C1 [Yu, Min; Miyamoto, David T.; Waltman, Belinda A.; Rothenberg, S. Michael; Smas, Malgorzata E.; Gilman, Anna J.; Lord, Jenna B.; Winokur, Daniel; Springer, Simeon; Sequist, Lecia V.; Lee, Richard J.; Isselbacher, Kurt J.; Maheswaran, Shyamala; Haber, Daniel A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Stott, Shannon L.; Hsu, Chia-Hsien; Tsukrov, Dina I.; Shah, Ajay M.; Korir, George K.; Floyd, Frederick P., Jr.; Irimia, Daniel; Nagrath, Sunitha; Toner, Mehmet] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Engn Med, Boston, MA 02114 USA. [Stott, Shannon L.; Hsu, Chia-Hsien; Irimia, Daniel; Nagrath, Sunitha; Toner, Mehmet] Harvard Univ, Sch Med, Shriners Hosp Children, Boston, MA 02114 USA. [Stott, Shannon L.; Hsu, Chia-Hsien; Irimia, Daniel; Nagrath, Sunitha; Maheswaran, Shyamala; Toner, Mehmet] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. [Miyamoto, David T.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. [Sequist, Lecia V.; Lee, Richard J.; Haber, Daniel A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Rothenberg, S. Michael; Haber, Daniel A.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. RP Isselbacher, KJ (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. EM kisselbacher@partners.org RI Hsu, Chia-Hsien/E-4957-2010; Hsu, Chia-Hsien /E-3946-2010; OI Irimia, Daniel/0000-0001-7347-2082 FU Prostate Cancer Foundation; National Institute for Biomedical Imaging and Bioengineering; National Institutes of Health/National Cancer Institute (NIH)/(NCI) [CA89138]; Ellison Foundation; AstraZeneca; Martell Foundation; Alex and Sonja Spier; Monell Foundation; American Cancer Society New England Division; NIH; Department of Defense; American Society of Clinical Oncology (ASCO) Cancer Foundation; Howard Hughes Medical Institute FX We express our gratitude to the all patients who participated in this study and the healthy volunteers who contributed blood samples. We are also grateful to Octavio Hurtado, Jochen Lennerz, Douglas Rubinson, Vijay Ambravaneswaran, Salil Desai, Ravi Kapur, John Walsh, Tom Barber, Justin Wong, Zev Nakamura, Matthew Ulman, Suchismita Paul, Brian Brannigan, Alessandra Moore, Maria Kempner, Brooke Nentwig, and Laura Libby for expert technical support. This work was supported by Dream Team Awards from the Prostate Cancer Foundation and Stand Up To Cancer (to D. A. H. and M. T.), a Quantum Grant from the National Institute for Biomedical Imaging and Bioengineering (to M. T.), National Institutes of Health/National Cancer Institute (NIH)/(NCI) Grant CA89138 (to S. M.), and generous donations from the Ellison Foundation, AstraZeneca, the Martell Foundation, Alex and Sonja Spier, the Monell Foundation, and institutional support from Massachusetts General Hospital. S. L. S. is supported through an American Cancer Society New England Division Research Grant, S.N. is supported through an NIH Director's New Innovator Award, R.J.L. is supported by a Physician Research Training Award (Department of Defense, Prostate Cancer Research Program) and a Career Development Award (The American Society of Clinical Oncology (ASCO) Cancer Foundation), and D.A.H. is supported by the Howard Hughes Medical Institute. NR 30 TC 591 Z9 624 U1 67 U2 434 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 26 PY 2010 VL 107 IS 43 BP 18392 EP 18397 DI 10.1073/pnas.1012539107 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 673QG UT WOS:000283677400033 PM 20930119 ER PT J AU Hellman, NE Liu, Y Merkel, E Austin, C Le Corre, S Beier, DR Sun, ZX Sharma, N Yoder, BK Drummond, IA AF Hellman, Nathan E. Liu, Yan Merkel, Erin Austin, Christina Le Corre, Stephanie Beier, David R. Sun, Zhaoxia Sharma, Neeraj Yoder, Bradley K. Drummond, Iain A. TI The zebrafish foxj1a transcription factor regulates cilia function in response to injury and epithelial stretch SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE pronephros; cystic kidney disease; neural injury; beat rate; ciliogenesis ID POLYCYSTIC KIDNEY-DISEASE; URINARY-TRACT OBSTRUCTION; RENAL CILIA; MORPHOLOGICAL-CHANGES; URETERAL OBSTRUCTION; PROTEOMIC ANALYSIS; EXOCRINE PANCREAS; TUBULAR CELLS; MOTILE CILIA; MOUSE MODEL AB Cilia are essential for normal organ function and developmental patterning, but their role in injury and regeneration responses is unknown. To probe therole of cilia in injury, we analyzed the function of foxj1, a transcriptional regulator of cilia genes, in response to tissue damage and renal cyst formation. Zebrafish foxj1a, but not foxj1b, was rapidly induced in response to epithelial distension and stretch, kidney cyst formation, acute kidney injury by gentamicin, and crush injury in spinal cord cells. Obstruction-inducedup-regulation of foxj1a was not inhibited by cycloheximide, identifying foxj1a as a primary response gene to epithelial injury. Foxj1 was also dramatically up-regulated in murine cystic kidney disease epithelia [jck/jck ( nek8) and Ift88Tg737Rpw(-/-)] as well as in response to kidney ischemia-reperfusion injury. Obstruction of the zebrafish pronephric tubule caused a rapid increase in cilia beat rate that correlated tightly with expanded tubule diameter and epithelial stretch. Zebrafish foxj1a was specifically required for cilia motility. Enhanced foxj1a expression in obstructed tubules induced ciliamotility target genes efhc1, tektin1, and dnahc9. foxj1a-deficient embryos failed to up-regulate efhc1, tektin-1, and dnahc9 and could not maintain enhanced cilia beat rates after obstruction, identifying an essential role for foxj1 in modulating cilia function after injury. These studies reveal that activation of a Foxj1 transcriptional network of ciliogenic genes is an evolutionarily conserved response to multiple forms of tissue damage and highlight enhanced cilia function as a previously uncharacterized component of organ homeostasis. C1 [Hellman, Nathan E.; Liu, Yan; Le Corre, Stephanie; Drummond, Iain A.] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02129 USA. [Merkel, Erin; Austin, Christina; Drummond, Iain A.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. [Beier, David R.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA. [Sun, Zhaoxia] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06515 USA. [Sharma, Neeraj; Yoder, Bradley K.] Univ Alabama, Sch Med, Dept Cell Biol, Birmingham, AL 35294 USA. RP Drummond, IA (reprint author), Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02129 USA. EM idrummon@receptor.mgh.harvard.edu FU National Institutes of Health [DK053093, DK065655, DK069528, DK066370, T32DK007540]; UAB Hepato/Renal Fibrocystic Diseases Core Center [P30 DK074038]; UAB O'Brien Core Center for Acute Kidney Injury Research [P30 DK079337] FX We thank personnel in the zebrafish facility at Massachusetts General Hospital, Randy Peterson for advice on quantitative PCR, Mingyue Lun for harvesting jck/jck mouse tissue, Christopher Ward (Mayo Clinic, Rochester, MN) for sharing Pkhd1-/- rat kidney tissue, and members of the I.A.D. laboratory for critical review and helpful discussions. This work was supported by National Institutes of Health Grants DK053093 (to I.A.D.), DK065655 (to B.K.Y.), DK069528 (to Z.S.), and DK066370 (to D.R. B.), National Institutes of Health Training Grant T32DK007540 (to N.E.H.), and by the UAB Hepato/Renal Fibrocystic Diseases Core Center (P30 DK074038) and the UAB O'Brien Core Center for Acute Kidney Injury Research (P30 DK079337). NR 59 TC 28 Z9 29 U1 0 U2 9 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 26 PY 2010 VL 107 IS 43 BP 18499 EP 18504 DI 10.1073/pnas.1005998107 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 673QG UT WOS:000283677400051 PM 20937855 ER PT J AU Tian, DQ Jacobo, SMP Billing, D Rozkalne, A Gage, SD Anagnostou, T Pavenstaedt, H Hsu, HH Schlondorff, J Ramos, A Greka, A AF Tian, Dequan Jacobo, Sarah M. P. Billing, David Rozkalne, Anete Gage, Steven D. Anagnostou, Theodora Pavenstaedt, Hermann Hsu, Hsiang-Hao Schlondorff, Johannes Ramos, Arnolt Greka, Anna TI Antagonistic Regulation of Actin Dynamics and Cell Motility by TRPC5 and TRPC6 Channels SO SCIENCE SIGNALING LA English DT Article ID FOCAL SEGMENTAL GLOMERULOSCLEROSIS; RECEPTOR POTENTIAL CHANNELS; KIDNEY PODOCYTES; CARDIAC-HYPERTROPHY; MAMMALIAN BRAIN; CATION CHANNEL; RHO-GTPASES; CYTOSKELETON; ACTIVATION; SYNAPTOPODIN AB The Rho family of small guanosine triphosphatases (Rho GTPases: RhoA, Cdc42, and Rac1) regulates many aspects of cell behavior, including actin dynamics and cell migration. The generation of calcium ion (Ca(2+)) microdomains is critical in promoting cell migration because they control the localized activity of Rho GTPases. We identified receptor-activated TRPC5 and TRPC6 (transient receptor potential canonical type 5 and 6) channels as antagonistic regulators of actin remodeling and cell motility in fibroblasts and kidney podocytes. We show that TRPC5 is in a molecular complex with Rac1, whereas TRPC6 is in a molecular complex with RhoA. TRPC5-mediated Ca(2+) influx induces Rac1 activation, thereby promoting cell migration, whereas TRPC6-mediated Ca(2+) influx increases RhoA activity, thereby inhibiting cell migration. Our data unveil antagonistic Ca(2+) influx pathways as a conserved signaling mechanism for the integrated regulation of cell migration. C1 [Tian, Dequan; Jacobo, Sarah M. P.; Billing, David; Rozkalne, Anete; Gage, Steven D.; Anagnostou, Theodora; Ramos, Arnolt; Greka, Anna] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Tian, Dequan; Jacobo, Sarah M. P.; Billing, David; Rozkalne, Anete; Gage, Steven D.; Anagnostou, Theodora; Ramos, Arnolt; Greka, Anna] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Pavenstaedt, Hermann] Med Klin & Poliklin D, D-48149 Munster, Germany. [Hsu, Hsiang-Hao] Chang Gung Mem Hosp & Univ, Tao Yuan 333, Taiwan. [Schlondorff, Johannes] Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. RP Greka, A (reprint author), Harvard Univ, Sch Med, Boston, MA 02114 USA. EM greka.anna@mgh.harvard.edu FU NephCure Foundation; NIH [DK083511] FX This work was supported by a Young Investigator Grant from the NephCure Foundation and NIH grant DK083511 (both to A.G.). NR 53 TC 108 Z9 109 U1 0 U2 4 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1937-9145 J9 SCI SIGNAL JI Sci. Signal. PD OCT 26 PY 2010 VL 3 IS 145 AR ra77 DI 10.1126/scisignal.2001200 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 674IP UT WOS:000283733600004 PM 20978238 ER PT J AU Federman, AD Woodward, M Keyhani, S AF Federman, Alex D. Woodward, Mark Keyhani, Salomeh TI Physicians' Opinions About Reforming Reimbursement Results of a National Survey SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID PAY-FOR-PERFORMANCE; CARE-SPECIALTY INCOME; HEALTH-CARE; PAYMENT POLICY; US PHYSICIANS; INSURANCE; VIEWS; PERSPECTIVE; QUALITY; OPTIONS AB Background: Several strategies have been proposed to reform physician reimbursement while improving quality of care. Despite much debate, physicians' opinions regarding reimbursement reform proposals have not been objectively assessed. Methods: We conducted a national survey of randomly selected physicians between June 25 and October 31, 2009. Physicians rated their support for several reimbursement reform proposals: rewarding quality with financial incentives, bundling payments for episodes of care, shifting payments from procedures to management and counseling services, increasing pay to generalists, and offsetting increased pay to generalists with a reduction in pay for other specialties. Support for the different reform options was compared with physician practice characteristics. Results: The response rate was 48.5% (n = 1222). Four of 5 physicians (78.4%) indicated that under Medicare, some procedures are compensated too highly and others are compensated at rates insufficient to cover costs. Incentives were the most frequently supported reform option (49.1%), followed by shifting payments (41.6%) and bundling (17.2%). Shifting payments and bundling were more commonly supported by generalists than by other specialists. There was broad support for increasing pay for generalists (79.8%), but a proposal to offset the increase with a 3% reduction in specialist reimbursement was supported by only 39.1% of physicians. Conclusions: Physicians are dissatisfied with Medicare reimbursement and show little consensus for major proposals to reform reimbursement. The successful adoption of payment reform proposals may require a better understanding of physicians' concerns and their willingness to make tradeoffs. Arch Intern Med. 2010;170(19):1735-1742 C1 [Federman, Alex D.; Woodward, Mark; Keyhani, Salomeh] Mt Sinai Sch Med, Div Gen Internal Med, New York, NY 10029 USA. [Keyhani, Salomeh] Mt Sinai Sch Med, Dept Hlth Policy, New York, NY 10029 USA. [Keyhani, Salomeh] James J Peters Vet Adm Med Ctr, Bronx, NY USA. RP Federman, AD (reprint author), Mt Sinai Sch Med, Div Gen Internal Med, POB 1087,1 Gustave L Levy Pl, New York, NY 10029 USA. EM alex.federman@mssm.edu FU Robert Wood Johnson Foundation; National Institute on Aging; National Heart, Lung, and Blood Institute; Veterans Administration Health Services Research and Development Service FX This project was supported by a grant from the Robert Wood Johnson Foundation and also by grants from the National Institute on Aging; the National Heart, Lung, and Blood Institute; and the Veterans Administration Health Services Research and Development Service (Drs Federman and Keyhani). NR 33 TC 4 Z9 4 U1 1 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD OCT 25 PY 2010 VL 170 IS 19 BP 1735 EP 1742 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 670PT UT WOS:000283440500009 PM 20975020 ER PT J AU Sweeney, B Wang, J Tambouret, R Wilbur, D AF Sweeney, Brenda Wang, Jessica Tambouret, Rosemary Wilbur, David TI The Use of P16/Ki67 Dual Immunostaining as an Adjunct to Routine Anal Cytology in Screening for Anal Squamous Intraepithelial Lesions SO CANCER CYTOPATHOLOGY LA English DT Meeting Abstract C1 [Sweeney, Brenda; Wang, Jessica; Tambouret, Rosemary; Wilbur, David] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1934-662X J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD OCT 25 PY 2010 VL 118 IS 5 SU S BP 324 EP 325 PG 2 WC Oncology; Pathology SC Oncology; Pathology GA 671DO UT WOS:000283480700029 ER PT J AU Ono, J Kindelberger, D Deshpande, V AF Ono, Jill Kindelberger, David Deshpande, Vikram TI Atypical Squamous Cells in the Urine: A Cause of False Positive Urine Cytology SO CANCER CYTOPATHOLOGY LA English DT Meeting Abstract C1 [Ono, Jill; Deshpande, Vikram] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kindelberger, David] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1934-662X J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD OCT 25 PY 2010 VL 118 IS 5 SU S BP 328 EP 329 PG 2 WC Oncology; Pathology SC Oncology; Pathology GA 671DO UT WOS:000283480700034 ER PT J AU Ono, J Knoepp, S Balassanian, R AF Ono, Jill Knoepp, Stewart Balassanian, Ronald TI Cyto-Immunostaining of Aspirate Smears Can Aid in the Diagnosis of Hodgkin Lymphoma by FNA Biopsy SO CANCER CYTOPATHOLOGY LA English DT Meeting Abstract C1 [Ono, Jill; Balassanian, Ronald] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Knoepp, Stewart] Univ Michigan, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1934-662X J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD OCT 25 PY 2010 VL 118 IS 5 SU S BP 375 EP 375 PG 1 WC Oncology; Pathology SC Oncology; Pathology GA 671DO UT WOS:000283480700100 ER PT J AU Chebib, I Turner, B Brugge, W Pitman, M AF Chebib, Ivan Turner, Brian Brugge, William Pitman, Martha TI Performance of PathfinderTG (R) CEA and Amylase Pancreatic Cyst Fluid Analysis SO CANCER CYTOPATHOLOGY LA English DT Meeting Abstract C1 [Chebib, Ivan; Pitman, Martha] Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Cytopathol Unit, Boston, MA 02114 USA. [Chebib, Ivan; Turner, Brian; Brugge, William; Pitman, Martha] Harvard Univ, Sch Med, Boston, MA USA. [Turner, Brian; Brugge, William] Massachusetts Gen Hosp, Dept Med, Div Gastroenterol, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1934-662X J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD OCT 25 PY 2010 VL 118 IS 5 SU S BP 376 EP 377 PG 2 WC Oncology; Pathology SC Oncology; Pathology GA 671DO UT WOS:000283480700103 ER PT J AU Chebib, I Pitman, M AF Chebib, Ivan Pitman, Martha TI Inspissated Mucin in EUS-FNA Aspirates from Pancreatic Cysts: A Potential Diagnostic Pitfall SO CANCER CYTOPATHOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Cytopathol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1934-662X J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD OCT 25 PY 2010 VL 118 IS 5 SU S BP 377 EP 377 PG 1 WC Oncology; Pathology SC Oncology; Pathology GA 671DO UT WOS:000283480700104 ER PT J AU Pitman, M Genevay, M Yaeger, K Chebib, I Turner, B Mino-Kenudson, M Brugge, W AF Pitman, Martha Genevay, Muriel Yaeger, Kurt Chebib, Ivan Turner, Brian Mino-Kenudson, Mari Brugge, William TI Atypical Epithelial Cells in EUS-FNAB Samples of Pancreatic Mucinous Cysts Correlates with a High Risk of Malignancy SO CANCER CYTOPATHOLOGY LA English DT Meeting Abstract C1 [Pitman, Martha; Genevay, Muriel; Yaeger, Kurt; Chebib, Ivan; Turner, Brian; Mino-Kenudson, Mari; Brugge, William] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1934-662X J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD OCT 25 PY 2010 VL 118 IS 5 SU S BP 381 EP 382 PG 2 WC Oncology; Pathology SC Oncology; Pathology GA 671DO UT WOS:000283480700109 ER PT J AU Chebib, I Wilbur, D AF Chebib, Ivan Wilbur, David TI Whole Slide Imaging in Gynecologic Cytology: A Feasibility Study Showing Potential for Use in Telecytology and Proficiency Testing SO CANCER CYTOPATHOLOGY LA English DT Meeting Abstract C1 Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Cytopathol Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1934-662X J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD OCT 25 PY 2010 VL 118 IS 5 SU S BP 385 EP 386 PG 2 WC Oncology; Pathology SC Oncology; Pathology GA 671DO UT WOS:000283480700115 ER PT J AU Evans, K Wolfe, J Tambouret, R Wilbur, D AF Evans, Karla Wolfe, Jeremy Tambouret, Rosemary Wilbur, David TI In the Blink of an Eye: Discrimination and Localization of Abnormalities in Cervical Cytology Screening from a Global Signal SO CANCER CYTOPATHOLOGY LA English DT Meeting Abstract C1 [Evans, Karla; Wolfe, Jeremy] Brigham & Womens Hosp, Boston, MA 02115 USA. [Tambouret, Rosemary; Wilbur, David] Massachusetts Gen Hosp, Boston, MA 02114 USA. RI Wolfe, Jeremy/C-1621-2012 OI Wolfe, Jeremy/0000-0002-6475-1984 NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1934-662X J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD OCT 25 PY 2010 VL 118 IS 5 SU S BP 389 EP 389 PG 1 WC Oncology; Pathology SC Oncology; Pathology GA 671DO UT WOS:000283480700119 ER PT J AU Tambouret, R Evans, K Wolfe, J Wilbur, D AF Tambouret, Rosemary Evans, Karla Wolfe, Jeremy Wilbur, David TI Have We Met Before? How Good Is Cytologists' Recognition Memory For Microscopic Images? SO CANCER CYTOPATHOLOGY LA English DT Meeting Abstract C1 [Tambouret, Rosemary; Wilbur, David] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Evans, Karla; Wolfe, Jeremy] Brigham & Womens Hosp, Boston, MA 02115 USA. RI Wolfe, Jeremy/C-1621-2012 OI Wolfe, Jeremy/0000-0002-6475-1984 NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1934-662X J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD OCT 25 PY 2010 VL 118 IS 5 SU S BP 389 EP 390 PG 2 WC Oncology; Pathology SC Oncology; Pathology GA 671DO UT WOS:000283480700121 ER PT J AU Wolfe, J Evans, K Evered, A Tambouret, R Wilbur, D AF Wolfe, Jeremy Evans, Karla Evered, Andrew Tambouret, Rosemary Wilbur, David TI Target Prevalence Influences Cytologists' Error Rates SO CANCER CYTOPATHOLOGY LA English DT Meeting Abstract C1 [Wolfe, Jeremy; Evans, Karla] Brigham & Womens Hosp, Boston, MA 02115 USA. [Tambouret, Rosemary; Wilbur, David] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Evered, Andrew] Cerv Screening Wales, Cardiff, S Glam, Wales. RI Wolfe, Jeremy/C-1621-2012 OI Wolfe, Jeremy/0000-0002-6475-1984 NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1934-662X J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD OCT 25 PY 2010 VL 118 IS 5 SU S BP 389 EP 389 PG 1 WC Oncology; Pathology SC Oncology; Pathology GA 671DO UT WOS:000283480700120 ER PT J AU Fischer, A Schwartz, M Schinstine, M Moriarty, A Clayton, A Wilbur, D Souers, R Fatheree, L AF Fischer, Andrew Schwartz, Mary Schinstine, Malcolm Moriarty, Ann Clayton, Amy Wilbur, David Souers, Rhona Fatheree, Lisa TI Immunohistochemistry Practices of Cytopathology Laboratories SO CANCER CYTOPATHOLOGY LA English DT Meeting Abstract C1 [Fischer, Andrew] Univ Massachusetts, Worcester, MA 01605 USA. [Schwartz, Mary] Methodist Hosp, Houston, TX 77030 USA. [Schinstine, Malcolm] Hilo Med Ctr, Hilo, HI USA. [Moriarty, Ann] AmeriPath Indiana, Indianapolis, IN USA. [Clayton, Amy] Mayo Clin, Div Anat Pathol, Rochester, MN USA. [Wilbur, David] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Souers, Rhona; Fatheree, Lisa] Coll Amer Pathologists, Northfield, IL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1934-662X J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD OCT 25 PY 2010 VL 118 IS 5 SU S BP 390 EP 391 PG 2 WC Oncology; Pathology SC Oncology; Pathology GA 671DO UT WOS:000283480700122 ER PT J AU Saban, KL Bryant, FB Reda, DJ Stroupe, KT Hynes, DM AF Saban, Karen L. Bryant, Fred B. Reda, Domenic J. Stroupe, Kevin T. Hynes, Denise M. TI Measurement invariance of the kidney disease and quality of life instrument (KDQOL-SF) across Veterans and non-Veterans SO HEALTH AND QUALITY OF LIFE OUTCOMES LA English DT Article ID STAGE RENAL-DISEASE; HEMODIALYSIS-PATIENTS; DIALYSIS OUTCOMES; PRACTICE PATTERNS; FIT INDEXES; FACTORIAL INVARIANCE; PSYCHOMETRIC PROPERTIES; COVARIANCE-STRUCTURES; PERITONEAL-DIALYSIS; HEALTH AB Background: Studies have demonstrated that perceived health-related quality of life (HRQOL) of patients receiving hemodialysis is significantly impaired. Since HRQOL outcome data are often used to compare groups to determine health care effectiveness it is imperative that measures of HRQOL are valid. However, valid HRQOL comparisons between groups can only be made if instrument invariance is demonstrated. The Kidney Disease Quality of Life Short Form (KDQOL-SF) is a widely used HRQOL measure for patients with chronic kidney disease (CKD) however, it has not been validated in the Veteran population. Therefore, the purpose of this study was to examine the measurement invariance of the KDQOL-SF across Veterans and non-Veterans with CKD. Methods: Data for this study were from two large prospective observational studies of patients receiving hemodialysis: 1) Veteran End-Stage Renal Disease Study (VETERAN) (N = 314) and 2) Dialysis Outcomes and Practice Patterns Study (DOPPS) (N = 3,300). Health-related quality of life was measured with the KDQOL-SF, which consists of the SF-36 and the Kidney Disease Component Summary (KDCS). Single-group confirmatory factor analysis was used to evaluate the goodness-of-fit of the hypothesized measurement model for responses to the subscales of the KDCS and SF-36 instruments when analyzed together; and given acceptable goodness-of-fit in each group, multigroup CFA was used to compare the structure of this factor model in the two samples. Pattern of factor loadings (configural invariance), the magnitude of factor loadings (metric invariance), and the magnitude of item intercepts (scalar invariance) were assessed as well as the degree to which factors have the same variances, covariances, and means across groups (structural invariance). Results: CFA demonstrated that the hypothesized two-factor model (KDCS and SF-36) fit the data of both the Veteran and DOPPS samples well, supporting configural invariance. Multigroup CFA results concerning metric and scalar invariance suggested partial strict invariance for the SF-36, but only weak invariance for the KDCS. Structural invariance was not supported. Conclusions: Results suggest that Veterans may interpret the KDQOL-SF differently than non-Veterans. Further evaluation of measurement invariance of the KDQOL-SF between Veterans and non-Veterans is needed using large, randomly selected samples before comparisons between these two groups using the KDQOL-SF can be done reliably. C1 [Saban, Karen L.; Stroupe, Kevin T.; Hynes, Denise M.] US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Ctr Management Chron Complex Care, Hines, IL 60141 USA. [Saban, Karen L.] Loyola Univ Chicago, Marcella Niehoff Sch Nursing, Maywood, IL USA. [Bryant, Fred B.] Loyola Univ Chicago, Dept Psychol, Chicago, IL USA. [Reda, Domenic J.] Vet Affairs Cooperat Studies Program Coordinating, Hines, IL USA. [Stroupe, Kevin T.; Hynes, Denise M.] Vet Affairs Informat Resource Ctr, Hines, IL USA. [Stroupe, Kevin T.] Loyola Univ, Stritch Sch Med, Maywood, IL 60153 USA. [Hynes, Denise M.] Univ Illinois, Coll Med, Chicago, IL USA. RP Saban, KL (reprint author), US Dept Vet Affairs, Vet Affairs Edward Hines Jr Hosp, Ctr Management Chron Complex Care, Roosevelt Rd & 5th Ave, Hines, IL 60141 USA. EM Ksaban@luc.edu OI Saban, Karen/0000-0001-5767-5453 FU U.S. Department of Veterans Affairs; Veterans Health Administration; Health Services Research and Development Service - "Cost and Effectiveness of End-Stage Renal Disease Care" [ECI 20 016]; Veterans Affairs Health Services Research and Development Service [TPN 42-001]; Amgen; Kyowa Hakko Kirin, Japan; Genzyme; Abbott FX This research was supported by the U.S. Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service - "Cost and Effectiveness of End-Stage Renal Disease Care" (D. Hynes, Principal Investigator) (ECI 20 016). Dr. Hynes is supported by a five-year Veterans Affairs Health Services Research and Development Service Research Career Scientist Award. Dr. Saban is supported by a three-year Veterans Affairs Health Services Research and Development Service Postdoctoral Fellowship (TPN 42-001). DOPPS data were provided by Arbor Research Collaborative for Health which administers and coordinates the Dialysis Outcomes and Practice Study. DOPPS is supported by scientific research from Amgen (since 1996), Kyowa Hakko Kirin (since 1999, in Japan), Genzyme (since 2009), and Abbott (since 2009), without restrictions on publications. We would like to thank Jenny Huo for her statistical assistance in performing multiple imputations. In addition, we would like to express our sincere gratitude to Dr. Albert Satorra (Departament d'Economia i Empresa, Universitat Pompeu Fabra) for his expert statistical guidance. Finally, we would like to acknowledge the anonymous reviewers for their insightful comments and suggestions concerning an earlier draft of this manuscript. NR 89 TC 8 Z9 9 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1477-7525 J9 HEALTH QUAL LIFE OUT JI Health Qual. Life Outcomes PD OCT 25 PY 2010 VL 8 AR 120 DI 10.1186/1477-7525-8-120 PG 16 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 724QC UT WOS:000287590300001 PM 20973987 ER PT J AU Helfrich, CD Damschroder, LJ Hagedorn, HJ Daggett, GS Sahay, A Ritchie, M Damush, T Guihan, M Ullrich, PM Stetler, CB AF Helfrich, Christian D. Damschroder, Laura J. Hagedorn, Hildi J. Daggett, Ginger S. Sahay, Anju Ritchie, Mona Damush, Teresa Guihan, Marylou Ullrich, Philip M. Stetler, Cheryl B. TI A critical synthesis of literature on the promoting action on research implementation in health services (PARIHS) framework SO IMPLEMENTATION SCIENCE LA English DT Review ID CONCEPTUAL-FRAMEWORK; PRACTICE GUIDELINES; CARE; CONTEXT; BEHAVIOR; FACILITATION; EXPLORATION; IMPROVEMENT; MANAGEMENT; OUTCOMES AB Background: The Promoting Action on Research Implementation in Health Services framework, or PARIHS, is a conceptual framework that posits key, interacting elements that influence successful implementation of evidence-based practices. It has been widely cited and used as the basis for empirical work; however, there has not yet been a literature review to examine how the framework has been used in implementation projects and research. The purpose of the present article was to critically review and synthesize the literature on PARIHS to understand how it has been used and operationalized, and to highlight its strengths and limitations. Methods: We conducted a qualitative, critical synthesis of peer-reviewed PARIHS literature published through March 2009. We synthesized findings through a three-step process using semi-structured data abstraction tools and group consensus. Results: Twenty-four articles met our inclusion criteria: six core concept articles from original PARIHS authors, and eighteen empirical articles ranging from case reports to quantitative studies. Empirical articles generally used PARIHS as an organizing framework for analyses. No studies used PARIHS prospectively to design implementation strategies, and there was generally a lack of detail about how variables were measured or mapped, or how conclusions were derived. Several studies used findings to comment on the framework in ways that could help refine or validate it. The primary issue identified with the framework was a need for greater conceptual clarity regarding the definition of sub-elements and the nature of dynamic relationships. Strengths identified included its flexibility, intuitive appeal, explicit acknowledgement of the outcome of 'successful implementation,' and a more expansive view of what can and should constitute 'evidence.' Conclusions: While we found studies reporting empirical support for PARIHS, the single greatest need for this and other implementation models is rigorous, prospective use of the framework to guide implementation projects. There is also need to better explain derived findings and how interventions or measures are mapped to specific PARIHS elements; greater conceptual discrimination among sub-elements may be necessary first. In general, it may be time for the implementation science community to develop consensus guidelines for reporting the use and usefulness of theoretical frameworks within implementation studies. C1 [Helfrich, Christian D.] VA Puget Sound Healthcare Syst, NW HSR&D Ctr Excellence, Seattle, WA USA. [Helfrich, Christian D.] Univ Washington, Sch Publ Hlth, Dept Hlth Serv, Seattle, WA 98195 USA. [Damschroder, Laura J.] VA Ann Arbor Healthcare Syst, HSR&D Ctr Clin Management Res & Diabet QUERI, Ann Arbor, MI USA. [Hagedorn, Hildi J.] Minneapolis VA Med Ctr, VA Substance Use Disorders Qual Enhancement Res I, Minneapolis, MN USA. [Hagedorn, Hildi J.] Univ Minnesota, Sch Med, Dept Psychiat, Minneapolis, MN 55455 USA. [Daggett, Ginger S.; Damush, Teresa] Richard L Roudebush VA Med Ctr, VA Stroke QUERI, HSR&D Ctr Excellence, Indianapolis, IN USA. [Sahay, Anju] VA Palo Alto Hlth Care Syst, Chron Heart Failure QUERI Ctr, Palo Alto, CA USA. [Ritchie, Mona] Cent Arkansas Vet Healthcare Syst, Mental Hlth Qual Enhancement Res Initiat, N Little Rock, AR USA. [Damush, Teresa] Indiana Univ, Ctr Aging Res, Regenstrief Inc, Indianapolis, IN 46204 USA. [Guihan, Marylou] Jr VA Hosp, Spinal Cord Injury QUERI Res Coordinating Ctr, Ctr Management Complex Chron Care CMC3, Hines, IL USA. [Ullrich, Philip M.] VA Puget Sound Hlth Care Syst, Spinal Cord Injury QUERI, Seattle, WA USA. [Stetler, Cheryl B.] Boston Univ, Sch Publ Hlth, Dept Hlth Serv, Boston, MA USA. RP Helfrich, CD (reprint author), VA Puget Sound Healthcare Syst, NW HSR&D Ctr Excellence, Seattle, WA USA. EM christian.helfrich@va.gov RI Helfrich, Christian/D-2382-2016; OI Helfrich, Christian/0000-0002-9827-4768; Damschroder, Laura/0000-0002-3657-8459 FU U.S. Department of Veterans Affairs, Office of Research and Development Health Services FX This material is based upon work supported by the U.S. Department of Veterans Affairs, Office of Research and Development Health Services R&D Program. We wish to acknowledge the important contributions of Jeffrey Smith to the paper, and the important administrative assistance of Jared LeClerc and Rachel Smith. Also, our thanks to Corrine Voils for providing invaluable feedback on a draft of the paper, and to Lars Wallin and Jacqueline Tetroe for their excellent reviews and suggestions. The views expressed in this article are the authors' and do not necessarily reflect the position or policy of the Department of Veterans Affairs. NR 61 TC 87 Z9 89 U1 3 U2 42 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1748-5908 J9 IMPLEMENT SCI JI Implement. Sci. PD OCT 25 PY 2010 VL 5 AR 82 DI 10.1186/1748-5908-5-82 PG 20 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 680KT UT WOS:000284231500001 PM 20973988 ER PT J AU Asikainen, S Dogan, B Turgut, Z Paster, BJ Bodur, A Oscarsson, J AF Asikainen, Sirkka Dogan, Basak Turgut, Zeynep Paster, Bruce J. Bodur, Aysen Oscarsson, Jan TI Specified Species in Gingival Crevicular Fluid Predict Bacterial Diversity SO PLOS ONE LA English DT Article ID PERSISTENT INFECTIONS; PERIODONTAL-DISEASE; CLONAL ANALYSIS; ORAL-CAVITY; MICROFLORA; IDENTIFICATION; INFLAMMATION; BIOFILMS; PLAQUE; MICROARRAY AB Background: Analysis of gingival crevicular fluid (GCF) samples may give information of unattached (planktonic) subgingival bacteria. Our study represents the first one targeting the identity of bacteria in GCF. Methodology/Principal Findings: We determined bacterial species diversity in GCF samples of a group of periodontitis patients and delineated contributing bacterial and host-associated factors. Subgingival paper point (PP) samples from the same sites were taken for comparison. After DNA extraction, 16S rRNA genes were PCR amplified and DNA-DNA hybridization was performed using a microarray for over 300 bacterial species or groups. Altogether 133 species from 41 genera and 8 phyla were detected with 9 to 62 and 18 to 64 species in GCF and PP samples, respectively, per patient. Projection to latent structures by means of partial least squares (PLS) was applied to the multivariate data analysis. PLS regression analysis showed that species of genera including Campylobacter, Selenomonas, Porphyromonas, Catonella, Tannerella, Dialister, Peptostreptococcus, Streptococcus and Eubacterium had significant positive correlations and the number of teeth with low-grade attachment loss a significant negative correlation to species diversity in GCF samples. OPLS/O2PLS discriminant analysis revealed significant positive correlations to GCF sample group membership for species of genera Campylobacter, Leptotrichia, Prevotella, Dialister, Tannerella, Haemophilus, Fusobacterium, Eubacterium, and Actinomyces. Conclusions/Significance: Among a variety of detected species those traditionally classified as Gram-negative anaerobes growing in mature subgingival biofilms were the main predictors for species diversity in GCF samples as well as responsible for distinguishing GCF samples from PP samples. GCF bacteria may provide new prospects for studying dynamic properties of subgingival biofilms. C1 [Asikainen, Sirkka; Oscarsson, Jan] Umea Univ, Inst Odontol, Sect Oral Microbiol, Umea, Sweden. [Dogan, Basak] Marmara Univ, Fac Dent, Dept Periodontol, Istanbul, Turkey. [Turgut, Zeynep; Bodur, Aysen] Gazi Univ, Dept Periodontol, Ankara, Turkey. [Paster, Bruce J.] Forsyth Inst, Dept Mol Genet, Boston, MA USA. [Paster, Bruce J.] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. RP Asikainen, S (reprint author), Kuwait Univ, Fac Dent, Safat, Kuwait. EM sirkka.asikainen@odont.umu.se FU Swedish Medical Research Council [2006-06X-14747-04-3/SA]; County Council of Vasterbotten, Sweden [VLL 1165-2005/SA] FX This work was funded by grants from the Swedish Medical Research Council 2006-06X-14747-04-3/SA, County Council of Vasterbotten, Sweden VLL 1165-2005/SA. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 35 TC 6 Z9 6 U1 0 U2 12 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD OCT 25 PY 2010 VL 5 IS 10 AR e13589 DI 10.1371/journal.pone.0013589 PG 12 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 670LB UT WOS:000283422100009 PM 21049043 ER PT J AU Caglayan, E Romeo, GR Kappert, K Odenthal, M Sudkamp, M Body, SC Shernan, SK Hackbusch, D Vantler, M Kazlauskas, A Rosenkranz, S AF Caglayan, Evren Romeo, Giulio R. Kappert, Kai Odenthal, Margarete Suedkamp, Michael Body, Simon C. Shernan, Stanton K. Hackbusch, Daniel Vantler, Marius Kazlauskas, Andrius Rosenkranz, Stephan TI Profilin-1 Is Expressed in Human Atherosclerotic Plaques and Induces Atherogenic Effects on Vascular Smooth Muscle Cells SO PLOS ONE LA English DT Article ID ACTIVATED RECEPTOR-GAMMA; ACTIN-BINDING PROTEIN; RAT MESANGIAL CELLS; GROWTH-FACTOR; INSULIN-RESISTANCE; DNA-SYNTHESIS; CHEMOTAXIS; INFLAMMATION; DYSFUNCTION; DISEASE AB Background: Profilin-1 is an ubiquitous actin binding protein. Under pathological conditions such as diabetes, profilin-1 levels are increased in the vascular endothelium. We recently demonstrated that profilin-1 overexpression triggers indicators of endothelial dysfunction downstream of LDL signaling, and that attenuated expression of profilin-1 confers protection from atherosclerosis in vivo. Methodology: Here we monitored profilin-1 expression in human atherosclerotic plaques by immunofluorescent staining. The effects of recombinant profilin-1 on atherogenic signaling pathways and cellular responses such as DNA synthesis (BrdU-incorporation) and chemotaxis (modified Boyden-chamber) were evaluated in cultured rat aortic and human coronary vascular smooth muscle cells (VSMCs). Furthermore, the correlation between profilin-1 serum levels and the degree of atherosclerosis was assessed in humans. Principal Findings: In coronary arteries from patients with coronary heart disease, we found markedly enhanced profilin expression in atherosclerotic plaques compared to the normal vessel wall. Stimulation of rat aortic and human coronary VSMCs with recombinant profilin-1 (10(-6) M) in vitro led to activation of intracellular signaling cascades such as phosphorylation of Erk1/2, p70(S6) kinase and PI3K/Akt within 10 minutes. Furthermore, profilin-1 concentration-dependently induced DNA-synthesis and migration of both rat and human VSMCs, respectively. Inhibition of PI3K (Wortmannin, LY294002) or Src-family kinases (SU6656, PP2), but not PLC gamma (U73122), completely abolished profilin-induced cell cycle progression, whereas PI3K inhibition partially reduced the chemotactic response. Finally, we found that profilin-1 serum levels were significantly elevated in patients with severe atherosclerosis in humans (p<0.001 vs. no atherosclerosis or control group). Conclusions: Profilin-1 expression is significantly enhanced in human atherosclerotic plaques compared to the normal vessel wall, and the serum levels of profilin-1 correlate with the degree of atherosclerosis in humans. The atherogenic effects exerted by profilin-1 on VSMCs suggest an auto-/paracrine role within the plaque. These data indicate that profilin-1 might critically contribute to atherogenesis and may represent a novel therapeutic target. C1 [Caglayan, Evren; Vantler, Marius; Rosenkranz, Stephan] Univ Cologne, Innere Med Klin 3, Cologne, Germany. [Caglayan, Evren; Vantler, Marius; Rosenkranz, Stephan] Univ Cologne, CMMC, Cologne, Germany. [Romeo, Giulio R.] Joslin Diabet Ctr, Dept Cellular & Mol Physiol, Boston, MA 02215 USA. [Kappert, Kai; Hackbusch, Daniel] Charite, CCR, Inst Pharmakol, D-13353 Berlin, Germany. [Odenthal, Margarete] Univ Cologne, Inst Pathol, D-5000 Cologne, Germany. [Suedkamp, Michael] Univ Freiburg Klinikum, Freiburg, Germany. [Body, Simon C.; Shernan, Stanton K.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Boston, MA 02115 USA. [Kazlauskas, Andrius] Harvard Univ, Schepens Eye Res Inst, Sch Med, Boston, MA USA. RP Caglayan, E (reprint author), Univ Cologne, Innere Med Klin 3, Cologne, Germany. EM stephan.rosenkranz@uk-koeln.de FU Deutsche Forschungsgemeinschaft [Ro 1306/2-1, Ro 1306/2-2]; Center for Molecular Medicine (CMMC) of the University of Cologne [A6]; Maria-Pesch-Stiftung; Medical Faculty; University of Cologne FX This work was supported in part by the Deutsche Forschungsgemeinschaft (to SR; Ro 1306/2-1 and 2-2), the Center for Molecular Medicine (CMMC) of the University of Cologne (to SR; A6), the Maria-Pesch-Stiftung (to EC), and by the Koeln Fortune Program (Medical Faculty; University of Cologne, to KK). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 28 TC 18 Z9 20 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD OCT 25 PY 2010 VL 5 IS 10 AR e13608 DI 10.1371/journal.pone.0013608 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 670LB UT WOS:000283422100015 PM 21049052 ER PT J AU Ripatti, S Tikkanen, E Orho-Melander, M Havulinna, AS Silander, K Sharma, A Guiducci, C Perola, M Jula, A Sinisalo, J Lokki, ML Nieminen, MS Melander, O Salomaa, V Peltonen, L Kathiresan, S AF Ripatti, Samuli Tikkanen, Emmi Orho-Melander, Marju Havulinna, Aki S. Silander, Kaisa Sharma, Amitabh Guiducci, Candace Perola, Markus Jula, Antti Sinisalo, Juha Lokki, Marja-Liisa Nieminen, Markku S. Melander, Olle Salomaa, Veikko Peltonen, Leena Kathiresan, Sekar TI A multilocus genetic risk score for coronary heart disease: case-control and prospective cohort analyses SO LANCET LA English DT Article ID HOSPITAL DISCHARGE REGISTER; CARDIOVASCULAR EVENTS; PREDICTIVE ABILITY; ARTERY-DISEASE; ROC CURVE; FOLLOW-UP; RECLASSIFICATION; MARKER; STATISTICS; MEDICINE AB Background Comparison of patients with coronary heart disease and controls in genome-wide association studies has revealed several single nucleotide polymorphisms (SNPs) associated with coronary heart disease. We aimed to establish the external validity of these findings and to obtain more precise risk estimates using a prospective cohort design. Methods We tested 13 recently discovered SNPs for association with coronary heart disease in a case-control design including participants differing from those in the discovery samples (3829 participants with prevalent coronary heart disease and 48 897 controls free of the disease) and a prospective cohort design including 30 725 participants free of cardiovascular disease from Finland and Sweden. We modelled the 13 SNPs as a multilocus genetic risk score and used Cox proportional hazards models to estimate the association of genetic risk score with incident coronary heart disease. For case-control analyses we analysed associations between individual SNPs and quintiles of genetic risk score using logistic regression. Findings In prospective cohort analyses, 1264 participants had a first coronary heart disease event during a median 10.7 years' follow-up (IQR 6.7-13.6). Genetic risk score was associated with a first coronary heart disease event. When compared with the bottom quintile of genetic risk score, participants in the top quintile were at 1.66-times increased risk of coronary heart disease in a model adjusting for traditional risk factors (95% CI 1.35-2.04, p value for linear trend=7.3x10(-10)). Adjustment for family history did not change these estimates. Genetic risk score did not improve C index over traditional risk factors and family history (p=0.19), nor did it have a significant effect on net reclassification improvement (2.2%, p=0.18); however, it did have a small effect on integrated discrimination index (0.004, p=0.0006). Results of the case-control analyses were similar to those of the prospective cohort analyses. Interpretation Using a genetic risk score based on 13 SNPs associated with coronary heart disease, we can identify the 20% of individuals of European ancestry who are at roughly 70% increased risk of a first coronary heart disease event. The potential clinical use of this panel of SNPs remains to be defined. C1 [Ripatti, Samuli; Tikkanen, Emmi; Silander, Kaisa; Peltonen, Leena] Univ Helsinki, FIMM, FIM-00014 Helsinki, Finland. [Ripatti, Samuli; Tikkanen, Emmi; Havulinna, Aki S.; Silander, Kaisa; Perola, Markus; Jula, Antti; Salomaa, Veikko; Peltonen, Leena] Natl Inst Hlth & Welf, Helsinki, Finland. [Orho-Melander, Marju; Sharma, Amitabh; Melander, Olle] Lund Univ, Dept Clin Sci Malmo, Malmo, Sweden. [Guiducci, Candace; Peltonen, Leena; Kathiresan, Sekar] Broad Inst, Cambridge, MA USA. [Sinisalo, Juha; Nieminen, Markku S.] Helsinki Univ Cent Hosp, Dept Med, Div Cardiol, Helsinki, Finland. [Lokki, Marja-Liisa] Univ Helsinki, Haartman Inst, Transplantat Lab, FIM-00014 Helsinki, Finland. [Peltonen, Leena] Wellcome Trust Sanger Inst, Hinxton, England. [Kathiresan, Sekar] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Kathiresan, Sekar] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. RP Ripatti, S (reprint author), Univ Helsinki, FIMM, POB 20, FIM-00014 Helsinki, Finland. EM samuli.ripatti@fimm.fi RI Max, Mad/E-5238-2010; Ripatti, Samuli/H-9446-2014; OI Max, Mad/0000-0001-6966-6829; Ripatti, Samuli/0000-0002-0504-1202; Perola, Markus/0000-0003-4842-1667; Sinisalo, Juha/0000-0002-0169-5137 FU Merck; Daiichi Sankyo; Alnylam; Pfizer; Wellcome Trust [WT089062/Z/097Z, WT089061/Z/09/Z]; US National Institutes of Health [R01 HL087676]; Donovan Family Foundation; Center of Excellence for Complex Disease Genetics of the Academy of Finland [213506, 129680]; Biocentrum Helsinki Foundation; Nordic Center of Excellence in Disease Genetics; Academy of Finland [129494]; Finnish Foundation for Cardiovascular Research; Sigrid Juselius Foundation; Finnish Academy [129322] FX SK has received consultancy fees from Merck and Daiichi Sankyo and grants from Alnylam and Pfizer. All other authors declare that they have no conflicts of interest.; We wish to dedicate this paper to the memory of Leena Peltonen, who passed away on March 11, 2010. This work was supported by the Wellcome Trust (WT089062/Z/097Z, WT089061/Z/09/Z), US National Institutes of Health (R01 HL087676), and the Donovan Family Foundation. We thank David Altshuler for guidance and helpful suggestions regarding study design and analyses. LP was supported by the Center of Excellence for Complex Disease Genetics of the Academy of Finland (grants 213506, 129680), the Biocentrum Helsinki Foundation, and The Nordic Center of Excellence in Disease Genetics. VS is supported by the Academy of Finland (grant number 129494), the Finnish Foundation for Cardiovascular Research, and the Sigrid Juselius Foundation. JS was funded by Finnish Foundation for Cardiovascular Research, Special governmental subsidy for health sciences research (EVO). MP was supported by Finnish Foundation for Cardiovascular Research and Finnish Academy Salve Program, grant number 129322 NR 29 TC 215 Z9 223 U1 1 U2 21 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD OCT 23 PY 2010 VL 376 IS 9750 BP 1393 EP 1400 DI 10.1016/S0140-6736(10)61267-6 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 672ZO UT WOS:000283627500034 PM 20971364 ER PT J AU Simarro, M Gimenez-Cassina, A Kedersha, N Lazaro, JB Adelmant, GO Marto, JA Rhee, K Tisdale, S Danial, N Benarafa, C Orduna, A Anderson, P AF Simarro, Maria Gimenez-Cassina, Alfredo Kedersha, Nancy Lazaro, Jean-Bernard Adelmant, Guillaume O. Marto, Jarrod A. Rhee, Kirsten Tisdale, Sarah Danial, Nika Benarafa, Charaf Orduna, Anonio Anderson, Paul TI Fast kinase domain-containing protein 3 is a mitochondrial protein essential for cellular respiration SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE FASTKD2; FASTKD3; Mitochondria; Respiration; Interactome; Mitochondrial respiratory chain complexes ID MAMMALIAN STRESS GRANULES; TIA-1; RNA; EXPRESSION; LOCALIZATION; PROMOTES; SEQUENCE; ALPHA AB Fas-activated serine/threonine phosphoprotein (FAST) is the founding member of the FAST kinase domain-containing protein (FASTKD) family that includes FASTKD1-5. FAST is a sensor of mitochondrial stress that modulates protein translation to promote the survival of cells exposed to adverse conditions. Mutations in FASTKD2 have been linked to a mitochondrial encephalomyopathy that is associated with reduced cytochrome c oxidase activity, an essential component of the mitochondrial electron transport chain. We have confirmed the mitochondrial localization of FASTKD2 and shown that all FASTKD family members are found in mitochondria. Although human and mouse FASTKD1-5 genes are expressed ubiquitously, some of them are most abundantly expressed in mitochondria-enriched tissues. We have found that RNA interference-mediated knockdown of FASTKD3 severely blunts basal and stress-induced mitochondrial oxygen consumption without disrupting the assembly of respiratory chain complexes. Tandem affinity purification reveals that FASTKD3 interacts with components of mitochondrial respiratory and translation machineries. Our results introduce FASTKD3 as an essential component of mitochondrial respiration that may modulate energy balance in cells exposed to adverse conditions by functionally coupling mitochondrial protein synthesis to respiration. (C) 2010 Elsevier Inc. All rights reserved. C1 [Simarro, Maria; Kedersha, Nancy; Rhee, Kirsten; Anderson, Paul] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. [Simarro, Maria; Kedersha, Nancy; Rhee, Kirsten; Anderson, Paul] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Gimenez-Cassina, Alfredo; Lazaro, Jean-Bernard; Adelmant, Guillaume O.; Marto, Jarrod A.; Tisdale, Sarah; Danial, Nika] Dana Farber Inst, Dept Canc Biol, Boston, MA 02115 USA. [Benarafa, Charaf] Univ Bern, Theodor Kocher Inst, CH-3012 Bern, Switzerland. [Orduna, Anonio] Univ Valladolid, Unidad Invest, Hosp Clin, E-47005 Valladolid, Spain. RP Anderson, P (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. EM panderson@rics.bwh.harvard.edu RI Simarro, Maria/M-3947-2015; OI Simarro, Maria/0000-0001-8917-7328; Gimenez-Cassina, Alfredo/0000-0002-2768-2350; Benarafa, Charaf/0000-0002-2049-7769 FU NIH [RO1 AR051472] FX The work was supported by RO1 AR051472 from the NIH (PA). NR 25 TC 17 Z9 25 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD OCT 22 PY 2010 VL 401 IS 3 BP 440 EP 446 DI 10.1016/j.bbrc.2010.09.075 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 676CR UT WOS:000283888200022 PM 20869947 ER PT J AU Qin, WP Pan, JP Bauman, WA Cardozo, CP AF Qin, Weiping Pan, Jiangping Bauman, William A. Cardozo, Christopher P. TI Differential alterations in gene expression profiles contribute to time-dependent effects of nandrolone to prevent denervation atrophy SO BMC GENOMICS LA English DT Article ID SKELETAL-MUSCLE ATROPHY; FOXO TRANSCRIPTION FACTORS; ANDROGEN RECEPTOR; MAMMALIAN TARGET; CARDIAC-HYPERTROPHY; RAPAMYCIN PATHWAY; UBIQUITIN LIGASES; KNOCKOUT MICE; FIBER-TYPE; F-BOX AB Background: Anabolic steroids, such as nandrolone, slow muscle atrophy, but the mechanisms responsible for this effect are largely unknown. Their effects on muscle size and gene expression depend upon time, and the cause of muscle atrophy. Administration of nandrolone for 7 days beginning either concomitantly with sciatic nerve transection (7 days) or 29 days later (35 days) attenuated denervation atrophy at 35 but not 7 days. We reasoned that this model could be used to identify genes that are regulated by nandrolone and slow denervation atrophy, as well as genes that might explain the time-dependence of nandrolone effects on such atrophy. Affymetrix microarrays were used to profile gene expression changes due to nandrolone at 7 and 35 days and to identify major gene expression changes in denervated muscle between 7 and 35 days. Results: Nandrolone selectively altered expression of 124 genes at 7 days and 122 genes at 35 days, with only 20 genes being regulated at both time points. Marked differences in biological function of genes regulated by nandrolone at 7 and 35 days were observed. At 35, but not 7 days, nandrolone reduced mRNA and protein levels for FOXO1, the mTOR inhibitor REDD2, and the calcineurin inhibitor RCAN2 and increased those for ApoD. At 35 days, correlations between mRNA levels and the size of denervated muscle were negative for RCAN2, and positive for ApoD. Nandrolone also regulated genes for Wnt signaling molecules. Comparison of gene expression at 7 and 35 days after denervation revealed marked alterations in the expression of 9 transcriptional coregulators, including Ankrd1 and 2, and many transcription factors and kinases. Conclusions: Genes regulated in denervated muscle after 7 days administration of nandrolone are almost entirely different at 7 versus 35 days. Alterations in levels of FOXO1, and of genes involved in signaling through calcineurin, mTOR and Wnt may be linked to the favorable action of nandrolone on denervated muscle. Marked changes in the expression of genes regulating transcription and intracellular signaling may contribute to the time-dependent effects of nandrolone on gene expression. C1 [Qin, Weiping; Pan, Jiangping; Bauman, William A.; Cardozo, Christopher P.] James J Peters VA Med Ctr, Ctr Excellence Med Consequences Spinal Cord Injur, Bronx, NY 10468 USA. [Qin, Weiping; Bauman, William A.; Cardozo, Christopher P.] Mt Sinai Sch Med, Dept Med, New York, NY 10029 USA. [Bauman, William A.; Cardozo, Christopher P.] Mt Sinai Sch Med, Dept Rehabil Med, New York, NY 10029 USA. RP Cardozo, CP (reprint author), James J Peters VA Med Ctr, Ctr Excellence Med Consequences Spinal Cord Injur, Room 1E-02,130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM chris.cardozo@mssm.edu FU Veterans Health Administration, Rehabilitation Research and Development Service [B4162C, B3347K, B3522R] FX The research reported here was supported by the Veterans Health Administration, Rehabilitation Research and Development Service (B4162C, B3347K, B3522R), which had no role in study design, data collection and interpretation, manuscript preparation or decisions to submit the manuscript. Microarray analysis was performed by the Microarray Core at the Mount Sinai School of Medicine. NR 78 TC 13 Z9 13 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PD OCT 22 PY 2010 VL 11 AR 596 DI 10.1186/1471-2164-11-596 PG 17 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 679PG UT WOS:000284172700001 PM 20969782 ER PT J AU Graham, JA Fray, M de Haseth, S Lee, KM Lian, MM Chase, CM Madsen, JC Markmann, J Benichou, G Colvin, RB Cosimi, AB Deng, SP Kim, J Alessandrini, A AF Graham, Jay A. Fray, Michael de Haseth, Stephanie Lee, Kang Mi Lian, Moh-Moh Chase, Catharine M. Madsen, Joren C. Markmann, James Benichou, Gilles Colvin, Robert B. Cosimi, A. Benedict Deng, Shaoping Kim, James Alessandrini, Alessandro TI Suppressive Regulatory T Cell Activity Is Potentiated by Glycogen Synthase Kinase 3 beta Inhibition SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANSCRIPTION FACTOR FOXP3; BETA-CATENIN; TGF-BETA; IN-VIVO; GSK3-BETA; STABILIZATION; PROLIFERATION; EXPRESSION; GSK-3-BETA; INDUCTION AB The mechanism by which regulatory T (Treg) cells suppress the immune response is not well defined. A recent study has shown that beta-catenin prolongs Treg cell survival. Because beta-catenin is regulated by glycogen synthase kinase 3 beta(GSK-3 beta)-directed phosphorylation, we focused on GSK-3 beta and the role it plays in Treg cell function. Inhibition of GSK-3 beta led to increased suppression activity by Treg cells. Inhibitor-treated Treg cells exhibited prolonged FoxP3 expression and increased levels of beta-catenin and of the antiapoptotic protein Bcl-xL. Systemic administration of GSK-3 beta inhibitor resulted in prolonged islet survival in an allotransplant mouse model. Our data suggest that GSK-3 beta could be a useful target in developing strategies designed to increase the stability and function of Treg cells for inducing allotransplant tolerance or treating autoimmune conditions. C1 [Madsen, Joren C.; Markmann, James; Benichou, Gilles; Cosimi, A. Benedict; Deng, Shaoping; Alessandrini, Alessandro] Harvard Univ, Sch Med, Transplantat Unit, Massachusetts Gen Hosp,Dept Surg, Boston, MA 02114 USA. [Colvin, Robert B.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Madsen, Joren C.] Massachusetts Gen Hosp, Div Cardiac Surg, Boston, MA 02114 USA. RP Alessandrini, A (reprint author), Harvard Univ, Sch Med, Transplantat Unit, Massachusetts Gen Hosp,Dept Surg, 55 Fruit St,Thier 807, Boston, MA 02114 USA. EM aalessandrini@partners.org RI Graham, Jay/A-4896-2014 OI Graham, Jay/0000-0003-2054-1253 FU National Institutes of Health [K01 DK079207-02, K02 AI53103, R01 HD050484, R01 HL071932, R01 AI048820-09, 5P01 HL18646, U19 DK080652, R01 AI081734-01]; Surgical Research Council FX This work was supported, in whole or in part, by National Institutes of Health Grants K01 DK079207-02 (to J.K.), K02 AI53103 and R01 HD050484 (to G. B.), R01 HL071932 (to J.C.M.), R01 AI048820-09 (to J.M.), 5P01 HL18646 and U19 DK080652 (to A. B. C.), and R01 AI081734-01 (to R. B. C.). This work was also supported by a Surgical Research Council junior faculty award (to A. A.). NR 39 TC 24 Z9 24 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 22 PY 2010 VL 285 IS 43 BP 32852 EP 32859 DI 10.1074/jbc.M110.150904 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 665PP UT WOS:000283048200022 PM 20729209 ER PT J AU Smagghe, BJ Huang, PS Ban, YEA Baker, D Springer, TA AF Smagghe, Benoit J. Huang, Po-Ssu Ban, Yih-En Andrew Baker, David Springer, Timothy A. TI Modulation of Integrin Activation by an Entropic Spring in the beta-Knee SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MONOCLONAL-ANTIBODY; STRUCTURAL BASIS; HYBRID DOMAIN; IN-VIVO; AFFINITY; RECEPTOR; BINDING; PROTEIN; CONFORMATION; SUBUNIT AB We show that the length of a loop in the beta-knee, between the first and second cysteines (C1-C2) in integrin EGF-like (I-EGF) domain 2, modulates integrin activation. Three independent sets of mutants, including swaps among different integrin beta-subunits, show that C1-C2 loop lengths of 12 and longer favor the low affinity state and masking of ligand-induced binding site (LIBS) epitopes. Shortening length from 12 to 4 residues progressively increases ligand binding and LIBS epitope exposure. Compared with length, the loop sequence had a smaller effect, which was ascribable to stabilizing loop conformation, and not interactions with the alpha-subunit. The data together with structural calculations support the concept that the C1-C2 loop is an entropic spring and an emerging theme that disordered regions can regulate allostery. Diversity in the length of this loop may have evolved among integrin beta-subunits to adjust the equilibrium between the bent and extended conformations at different set points. C1 [Smagghe, Benoit J.; Springer, Timothy A.] Childrens Hosp Boston, Immune Dis Inst, Boston, MA 02115 USA. [Smagghe, Benoit J.; Springer, Timothy A.] Harvard Univ, Dept Pathol, Sch Med, Boston, MA 02115 USA. [Huang, Po-Ssu; Ban, Yih-En Andrew; Baker, David] Univ Washington, Dept Biochem, Seattle, WA 98195 USA. [Huang, Po-Ssu; Ban, Yih-En Andrew; Baker, David] Univ Washington, Howard Hughes Med Inst, Seattle, WA 98195 USA. RP Springer, TA (reprint author), Childrens Hosp Boston, Immune Dis Inst, Boston, MA 02115 USA. EM springer@idi.harvard.edu RI Baker, David/K-8941-2012 OI Baker, David/0000-0001-7896-6217 FU National Institutes of Health [HL-48675] FX This work was supported, in whole or in part, by National Institutes of Health Grant HL-48675. NR 49 TC 21 Z9 22 U1 1 U2 7 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 22 PY 2010 VL 285 IS 43 BP 32954 EP 32966 DI 10.1074/jbc.M110.145177 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 665PP UT WOS:000283048200033 PM 20670939 ER PT J AU Gandhi, G Londono, D Whetstine, CR Sethi, N Kim, KS Zuckert, WR Cadavid, D AF Gandhi, Gaurav Londono, Diana Whetstine, Christine R. Sethi, Nilay Kim, Kwang S. Zueckert, Wolfram R. Cadavid, Diego TI Interaction of Variable Bacterial Outer Membrane Lipoproteins with Brain Endothelium SO PLOS ONE LA English DT Article ID RELAPSING FEVER SPIROCHETE; ESCHERICHIA-COLI INVASION; NECROSIS-FACTOR-ALPHA; BORRELIA-BURGDORFERI; TRANSENDOTHELIAL MIGRATION; IN-VITRO; PERSISTENT INFECTION; NEUROTROPIC STRAIN; CRYSTAL-STRUCTURE; SURFACE PROTEIN AB Background: Previously we reported that the variable outer membrane lipoprotein Vsp1 from the relapsing fever spirochete Borrelia turicatae disseminates from blood to brain better than the closely related Vsp2 [1]. Here we studied the interaction between Vsp1 and Vsp2 with brain endothelium in more detail. Methodology/Principal Findings: We compared Vsp1 to Vsp2 using human brain microvascular endothelial cell (HBMEC) association assays with aminoacid radiolabeled Vsp-expressing clones of recombinant Borrelia burgdorferi and lanthanide-labeled purified lipidated Vsp1 (LVsp1) and Vsp2 (LVsp2) and inoculations of the lanthanide-labeled proteins into mice. The results showed that heterologous expression of LVsp1 or LVsp2 in B. burgdorferi increased its association with HBMEC to a similar degree. Purified lanthanide- labeled lipidated Vsp1 (LVsp1) and LVsp2 by themselves were capable of associating with HBMEC. The association of LVsp1 with brain endothelium was time-dependent, saturable, and required the lipidation. The association of Vsp1 with HBMEC was inhibited by incubation at lower temperature or with excess unlabeled LVsp1 or LVsp2 but not with excess rVsp1 or mouse albumin or an anti Vsp1 monoclonal antibody. The association of LVsp2 with HBMEC and its movement from blood to brain parenchyma significantly increased in the presence of LVsp1. Conclusions/Significance: Variable bacterial outer membrane lipoproteins interact with brain endothelium differently; the lipidation and variable features at the protein dome region are key modulators of this interaction. C1 [Gandhi, Gaurav; Londono, Diana; Sethi, Nilay; Cadavid, Diego] UMDNJ New Jersey Med Sch, Dept Neurol & Neurosci, Newark, NJ USA. [Gandhi, Gaurav; Londono, Diana; Sethi, Nilay; Cadavid, Diego] UMDNJ New Jersey Med Sch, Ctr Study Emerging Pathogens, Newark, NJ USA. [Londono, Diana; Cadavid, Diego] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA. [Whetstine, Christine R.; Zueckert, Wolfram R.] Univ Kansas, Med Ctr, Dept Microbiol Mol Genet & Immunol, Kansas City, KS 66103 USA. [Kim, Kwang S.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. RP Gandhi, G (reprint author), UMDNJ New Jersey Med Sch, Dept Neurol & Neurosci, Newark, NJ USA. EM dcadavid@partners.org FU National Institutes of Health [NS053997, 7R21NS057545-02, AI059468, AI063261]; Foundation of UMDNJ FX These studies were supported by National Institutes of Health grants NS053997 and 7R21NS057545-02 to D. C. and AI059468 and AI063261 to W. R. Z. The support of the Foundation of UMDNJ to D. C. is also greatly appreciated. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 67 TC 4 Z9 4 U1 0 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD OCT 22 PY 2010 VL 5 IS 10 AR e13257 DI 10.1371/journal.pone.0013257 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 670KA UT WOS:000283419100002 PM 21063459 ER PT J AU Breakefield, XO Sena-Esteves, M AF Breakefield, Xandra O. Sena-Esteves, Miguel TI Healing Genes in the Nervous System SO NEURON LA English DT Editorial Material ID DISEASE; THERAPY; DELIVERY; BRAIN; CELLS; MICE AB The evolution of gene therapy has led to the development of promising new therapeutic approaches. This NeuroView will introduce the variety of delivery vehicles currently available for gene therapy, a range of preclinical strategies for tackling major diseases of the nervous system, the clinical limitations, and ethical considerations. C1 [Breakefield, Xandra O.] Harvard Univ, Sch Med, Ctr Neurosci, Boston, MA 02114 USA. [Breakefield, Xandra O.] Harvard Univ, Sch Med, Dept Neurol, Mol Neurogenet Unit, Boston, MA 02115 USA. [Breakefield, Xandra O.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp,Ctr Mol Imaging Res, Boston, MA 02115 USA. [Breakefield, Xandra O.] Harvard Univ, Sch Med, Program Neurosci, Boston, MA 02115 USA. [Sena-Esteves, Miguel] Univ Massachusetts, Sch Med, Interdisciplinary Grad Program, Gene Therapy Ctr,Dept Neurol, Worcester, MA 01605 USA. RP Breakefield, XO (reprint author), Harvard Univ, Sch Med, Ctr Neurosci, Boston, MA 02114 USA. EM breakefield@hms.harvard.edu FU NCI NIH HHS [P01 CA069246, CA069246]; NICHD NIH HHS [R01 HD060576, R01HD060576]; NINDS NIH HHS [NS24279, P01 NS037409, R01NS066310, U01NS064096, R01 NS066310, NS037409, P01 NS024279, P01 NS024279-23, U01 NS064096] NR 13 TC 2 Z9 2 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 J9 NEURON JI Neuron PD OCT 21 PY 2010 VL 68 IS 2 BP 178 EP 181 DI 10.1016/j.neuron.2010.10.005 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 681IJ UT WOS:000284304300004 PM 20955923 ER PT J AU Bertram, L Lill, CM Tanzi, RE AF Bertram, Lars Lill, Christina M. Tanzi, Rudolph E. TI The Genetics of Alzheimer Disease: Back to the Future SO NEURON LA English DT Review ID GENOME-WIDE ASSOCIATION; AMYLOID PRECURSOR PROTEIN; APOLIPOPROTEIN-E GENOTYPE; A-BETA; SYSTEMATIC METAANALYSES; MACULAR DEGENERATION; SUSCEPTIBILITY GENES; IDENTIFIES VARIANTS; INCREASED FREQUENCY; PARKINSONS-DISEASE AB Three decades of genetic research in Alzheimer disease (AD) have substantially broadened our understanding of the pathogenetic mechanisms leading to neurodegeneration and dementia. Positional cloning led to the identification of rare, disease-causing mutations in APP, PSEN1, and PSEN2 causing early-onset familial AD, followed by the discovery of APOE as the single most important risk factor for late-onset AD. Recent genome-wide association approaches have delivered several additional AD susceptibility loci that are common in the general population, but exert only very small risk effects. As a result, a large proportion of the heritability of AD continues to remain unexplained by the currently known disease genes. It seems likely that much of this "missing heritability" may be accounted for by rare sequence variants, which, owing to recent advances in high-throughput sequencing technologies, can now be assessed in unprecedented detail. C1 [Bertram, Lars; Lill, Christina M.] Max Planck Inst Mol Genet, Dept Vertebrate Genom, Berlin, Germany. [Lill, Christina M.] Johannes Gutenberg Univ Mainz, Dept Neurol, Mainz, Germany. [Tanzi, Rudolph E.] Harvard Univ, Sch Med, Massachusetts Gen Hosp,Genet & Aging Res Unit, MassGen Inst Neurodegenerat Dis,Dept Neurol, Charlestown, MA 02129 USA. RP Bertram, L (reprint author), Max Planck Inst Mol Genet, Dept Vertebrate Genom, Berlin, Germany. EM bertram@molgen.mpg.de RI Lill, Christina/J-9449-2015; Bertram, Lars/K-3889-2015 OI Lill, Christina/0000-0002-2805-1307; Bertram, Lars/0000-0002-0108-124X FU NIMH, NIA; German Federal Ministry of Education and Research (BMBF); Cure Alzheimer's Fund FX This work was made possible by support from the Cure Alzheimer's Fund, NIMH, NIA, and the German Federal Ministry of Education and Research (BMBF). The AlzGene database is funded by the Cure Alzheimer's Fund. We thank Dr. U.F. for his continuing inspiration and helpful comments on the manuscript. R.E.T. serves as consultant to Pathway Genomics. NR 114 TC 357 Z9 367 U1 13 U2 105 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0896-6273 J9 NEURON JI Neuron PD OCT 21 PY 2010 VL 68 IS 2 BP 270 EP 281 DI 10.1016/j.neuron.2010.10.013 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 681IJ UT WOS:000284304300015 PM 20955934 ER PT J AU Ferris, TG Torchiana, DF AF Ferris, Timothy G. Torchiana, David F. TI Public Release of Clinical Outcomes Data -- Online CABG Report Cards. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID QUALITY MEASUREMENT; SURGERY C1 [Ferris, Timothy G.; Torchiana, David F.] Massachusetts Gen Hosp, Massachusetts Gen Phys Org, Boston, MA 02114 USA. RP Ferris, TG (reprint author), Massachusetts Gen Hosp, Massachusetts Gen Phys Org, Boston, MA 02114 USA. NR 4 TC 44 Z9 45 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 OCT 21 PY 2010 VL 363 IS 17 BP 1593 EP 1595 DI 10.1056/NEJMp1009423 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 668BD UT WOS:000283242700003 PM 20961241 ER PT J AU Bloom, SL Uppot, R Roberts, DJ AF Bloom, Steven L. Uppot, Raul Roberts, Drucilla J. TI Case 32-2010: A Pregnant Woman with Abdominal Pain and Fluid in the Peritoneal Cavity. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID SEGMENTAL MEDIOLYTIC ARTERIOPATHY; SPLENIC ARTERY ANEURYSM; ECTOPIC DECIDUA; UTERINE ARTERY; SPONTANEOUS RUPTURE; HEMORRHAGE; VASCULITIS; DISEASE C1 [Bloom, Steven L.] Univ Texas SW Med Ctr Dallas, Dept Obstet & Gynecol, Dallas, TX 75390 USA. [Uppot, Raul] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Roberts, Drucilla J.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Uppot, Raul] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02115 USA. [Roberts, Drucilla J.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Bloom, SL (reprint author), Univ Texas SW Med Ctr Dallas, Dept Obstet & Gynecol, Dallas, TX 75390 USA. NR 24 TC 1 Z9 1 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 OCT 21 PY 2010 VL 363 IS 17 BP 1657 EP 1665 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 668BD UT WOS:000283242700012 PM 20961250 ER PT J AU Nagesha, DK Tada, DB Stambaugh, CKK Gultepe, E Jost, E Levy, CO Cormack, R Makrigiorgos, GM Sridhar, S AF Nagesha, D. K. Tada, D. B. Stambaugh, C. K. K. Gultepe, E. Jost, E. Levy, C. O. Cormack, R. Makrigiorgos, G. M. Sridhar, S. TI Radiosensitizer-eluting nanocoatings on gold fiducials for biological in-situ image-guided radio therapy (BIS-IGRT) SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID DELIVERY-SYSTEMS; CANCER-THERAPY; DRUG; RELEASE; CHITOSAN; RADIOTHERAPY; PROSTATE; BEADS AB Image-guided radiation treatments (IGRT) routinely utilize radio-opaque implantable devices, such as fiducials or brachytherapy spacers, for improved spatial accuracy. The therapeutic efficiency of IGRT can be further enhanced by biological in situ dose painting (BIS-IGRT) of radiosensitizers through localized delivery within the tumor using gold fiducial markers that have been coated with nanoporous polymer matrices loaded with nanoparticles (NPs). In this work, two approaches were studied: (i) a free drug release system consisting of Doxorubicin (Dox), a hydrophilic drug, loaded into a non-degradable polymer poly(methyl methacrylate) (PMMA) coating and (ii) poly(D,L-lactic-co-glycolic acid) (PLGA) NPs loaded with fluorescent Coumarin-6, serving as a model for a hydrophobic drug, in a biodegradable chitosan matrix. Temporal release kinetics measurements in buffer were carried out using fluorescence spectroscopy. In the first case of free Dox release, an initial release within the first few hours was followed by a sustained release over the course of the next 3 months. In the second platform, release of NPs and the free drug was controlled by the degradation rate of the chitosan matrix and PLGA. The results show that dosage and rate of release of these radiosensitizers coated on gold fiducials for IGRT can be precisely tailored to achieve the desired release profile for radiation therapy of cancer. C1 [Nagesha, D. K.; Tada, D. B.; Stambaugh, C. K. K.; Gultepe, E.; Jost, E.; Levy, C. O.; Sridhar, S.] Northeastern Univ, Elect Mat Res Inst, Boston, MA 02115 USA. [Nagesha, D. K.; Tada, D. B.; Stambaugh, C. K. K.; Gultepe, E.; Jost, E.; Levy, C. O.; Sridhar, S.] Northeastern Univ, Dept Phys, Boston, MA 02115 USA. [Cormack, R.; Makrigiorgos, G. M.; Sridhar, S.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dana Farber Canc Inst,Dept Radiat Oncol, Boston, MA 02115 USA. RP Sridhar, S (reprint author), Northeastern Univ, Elect Mat Res Inst, Boston, MA 02115 USA. EM s.sridhar@neu.edu RI Sridhar, Srinivas/A-3688-2012; Tada, Dayane/E-9032-2012; OI Cormack, Robert/0000-0001-5553-9984 FU Kayes Scholars Award; Dana Farber-Brigham and Women's Cancer Center; Electronics Materials Research Institute at Northeastern University; [NSF-DGE-0504331] FX We thank the anonymous referees for numerous suggestions regarding the paper. This work was supported by the Nanomedicine Science and Technology Program (NSF-DGE-0504331), by a Kayes Scholars Award, by Dana Farber-Brigham and Women's Cancer Center and Electronics Materials Research Institute at Northeastern University. NR 24 TC 8 Z9 9 U1 1 U2 8 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD OCT 21 PY 2010 VL 55 IS 20 BP 6039 EP 6052 DI 10.1088/0031-9155/55/20/001 PG 14 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 659WW UT WOS:000282599000001 PM 20858923 ER PT J AU Bao, XR Fraser, IDC Wall, EA Quake, SR Simon, MI AF Bao, Xiaoyan Robert Fraser, Iain D. C. Wall, Estelle A. Quake, Stephen R. Simon, Melvin I. TI Variability in G-Protein-Coupled Signaling Studied with Microfluidic Devices SO BIOPHYSICAL JOURNAL LA English DT Article ID TO-CELL VARIABILITY; GENE-EXPRESSION; SINGLE-CELL; P2Y(6) RECEPTOR; DYNAMICS; MACROPHAGES; PLATFORM; CALCIUM; C5A; UDP AB Different cells, even those that are genetically identical, can respond differently to identical stimuli, but the precise source of this variability remains obscure. To study this problem, we built a microfluidic experimental system which can track responses of individual cells across multiple stimulations. We used this system to determine that amplitude variation in G-protein-activated calcium release in RAW264.7 macrophages is generally extrinsic, i.e., they arise from long-lived variations between cells and not from stochastic activation of signaling components. In the case of responses linked to P2Y family purine receptors, we estimate that approximately one-third of the observed variability in calcium release is receptor-specific. We further demonstrate that the signaling apparatus downstream of P2Y6 receptor activation is moderately saturable. These observations will be useful in constructing and constraining single-cell models of G protein-coupled calcium dynamics. C1 [Bao, Xiaoyan Robert] CALTECH, Dept Appl Phys, Pasadena, CA 91125 USA. [Fraser, Iain D. C.; Wall, Estelle A.; Simon, Melvin I.] CALTECH, Div Biol, Pasadena, CA 91125 USA. [Bao, Xiaoyan Robert] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Wall, Estelle A.; Simon, Melvin I.] Univ Calif San Diego, Dept Pharmacol, La Jolla, CA 92093 USA. [Quake, Stephen R.] Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA. RP Bao, XR (reprint author), CALTECH, Dept Appl Phys, Pasadena, CA 91125 USA. EM bao@chgr.mgh.harvard.edu OI Bao, Xiaoyan/0000-0001-7931-2944 FU National Institute of General Medical Sciences Glue Grant Initiative [U54 GM062114]; Ellison Medical Foundation; Fannie and John Hertz Foundation FX This work was funded in part by the National Institute of General Medical Sciences Glue Grant Initiative (No. U54 GM062114), and by a Senior Scholar award in Aging from the Ellison Medical Foundation to M.I.S. X.R.B. acknowledges support from the Fannie and John Hertz Foundation. NR 34 TC 16 Z9 16 U1 0 U2 7 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD OCT 20 PY 2010 VL 99 IS 8 BP 2414 EP 2422 DI 10.1016/j.bpj.2010.08.043 PG 9 WC Biophysics SC Biophysics GA 670HT UT WOS:000283412500007 PM 20959081 ER PT J AU Neily, J Mills, PD Young-Xu, YN Carney, BT West, P Berger, DH Mazzia, LM Paull, DE Bagian, JP AF Neily, Julia Mills, Peter D. Young-Xu, Yinong Carney, Brian T. West, Priscilla Berger, David H. Mazzia, Lisa M. Paull, Douglas E. Bagian, James P. TI Association Between Implementation of a Medical Team Training Program and Surgical Mortality SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID PROPENSITY SCORE; OPERATING-ROOM; RISK ADJUSTMENT; CARE; COMMUNICATION; MORBIDITY; SURGERY; QUALITY; SAFETY; BRIEFINGS AB Context There is insufficient information about the effectiveness of medical team training on surgical outcomes. The Veterans Health Administration (VHA) implemented a formalized medical team training program for operating room personnel on a national level. Objective To determine whether an association existed between the VHA Medical Team Training program and surgical outcomes. Design, Setting, and Participants A retrospective health services study with a contemporaneous control group was conducted. Outcome data were obtained from the VHA Surgical Quality Improvement Program (VASQIP) and from structured interviews in fiscal years 2006 to 2008. The analysis included 182 409 sampled procedures from 108 VHA facilities that provided care to veterans. The VHA's nationwide training program required briefings and debriefings in the operating room and included checklists as an integral part of this process. The training included 2 months of preparation, a 1-day conference, and 1 year of quarterly coaching interviews Main Outcome Measure The rate of change in the mortality rate 1 year after facilities enrolled in the training program compared with the year before and with non-training sites. Results The 74 facilities in the training program experienced an 18% reduction in annual mortality (rate ratio [RR], 0.82; 95% confidence interval [CI], 0.76-0.91; P=.01) compared with a 7% decrease among the 34 facilities that had not yet undergone training (RR, 0.93; 95% CI, 0.80-1.06; P=.59). The risk-adjusted mortality rates at baseline were 17 per 1000 procedures per year for the trained facilities and 15 per 1000 procedures per year for the nontrained facilities. At the end of the study, the rates were 14 per 1000 procedures per year for both groups. Propensity matching of the trained and nontrained groups demonstrated that the decline in the risk-adjusted surgical mortality rate was about 50% greater in the training group (RR, 1.49; 95% CI, 1.10-2.07; P=.01) than in the nontraining group. A dose-response relationship for additional quarters of the training program was also demonstrated: for every quarter of the training program, a reduction of 0.5 deaths per 1000 procedures occurred (95% CI, 0.2-1.0; P=.001). Conclusion Participation in the VHA Medical Team Training program was associated with lower surgical mortality. JAMA. 2010; 304(15): 1693-1700 C1 [Neily, Julia; Mills, Peter D.; Young-Xu, Yinong; Carney, Brian T.; West, Priscilla; Mazzia, Lisa M.; Paull, Douglas E.; Bagian, James P.] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Vet Affairs,Natl Ctr Patient Safety, Hanover, NH 03756 USA. [Mills, Peter D.; Young-Xu, Yinong] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Dept Psychiat, Hanover, NH 03756 USA. [Berger, David H.] Baylor Coll Med, Dept Surg, Houston, TX 77030 USA. [Berger, David H.] Baylor Coll Med, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. [Bagian, James P.] Univ Texas Med Branch, Galveston, TX USA. [Bagian, James P.] Uniformed Serv Univ Hlth Sci, F Edward Hebert Sch Med, Bethesda, MD 20814 USA. RP Neily, J (reprint author), 215 N Main St, White River Jct, VT 05009 USA. EM Julia.Neily@va.gov NR 32 TC 325 Z9 331 U1 4 U2 19 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD OCT 20 PY 2010 VL 304 IS 15 BP 1693 EP 1700 DI 10.1001/jama.2010.1506 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 666PZ UT WOS:000283129700023 PM 20959579 ER PT J AU Jha, AK AF Jha, Ashish K. TI Meaningful Use of Electronic Health Records The Road Ahead SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID CARE C1 [Jha, Ashish K.] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Jha, Ashish K.] Brigham & Womens Hosp, Div Gen Med, Boston, MA 02115 USA. [Jha, Ashish K.] VA Boston Healthcare Syst, Boston, MA USA. RP Jha, AK (reprint author), Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, 677 Huntington Ave, Boston, MA 02115 USA. EM ajha@hsph.harvard.edu NR 10 TC 64 Z9 64 U1 0 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD OCT 20 PY 2010 VL 304 IS 15 BP 1709 EP 1710 DI 10.1001/jama.2010.1497 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 666PZ UT WOS:000283129700025 PM 20959581 ER PT J AU Sun, D Lye-Barthel, M Masland, RH Jakobs, TC AF Sun, Daniel Lye-Barthel, Ming Masland, Richard H. Jakobs, Tatjana C. TI Structural Remodeling of Fibrous Astrocytes after Axonal Injury SO JOURNAL OF NEUROSCIENCE LA English DT Article ID SPINAL-CORD-INJURY; RAT OPTIC-NERVE; GANGLION-CELL DEGENERATION; REACTIVE ASTROCYTES; CRUSH INJURY; DBA/2J MICE; TRANSGENIC MICE; NEURONAL DEATH; SCAR FORMATION; GLIAL-CELLS AB Reactive astrocytes are a pathological hallmark of many CNS injuries and neurodegenerations. They are characterized by hypertrophy of the soma and processes and an increase in the expression of glial fibrillary acidic protein. Because the cells obscure each other in immunostaining, little is known about the behavior of a single reactive astrocyte, nor how single astrocytes combine to form the glial scar. We have investigated the reaction of fibrous astrocytes to axonal degeneration using a transgenic mouse strain expressing enhanced green fluorescent protein in small subsets of astrocytes. Fibrous astrocytes in the optic nerve and corpus callosum initially react to injury by hypertrophy of the soma and processes. They retract their primary processes, simplifying their shape and dramatically reducing their spatial coverage. At 3 d after crush, quantitative analysis revealed nearly a twofold increase in the thickness of the primary processes, a halving of the number of primary processes leaving the soma and an eightfold reduction in the spatial coverage. In the subsequent week, they partially reextend long processes, returning to a near-normal morphology and an extensive spatial overlap. The resulting glial scar consists of an irregular array of astrocyte processes, contrasting with their original orderly arrangement. These changes are in distinct contrast to those reported for reactive protoplasmic astrocytes of the gray matter, in which the number of processes and branchings increase, but the cells continue to maintain nonoverlapping individual territories throughout their response to injury. C1 [Sun, Daniel] Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. RP Sun, D (reprint author), Harvard Univ, Sch Med, Massachusetts Eye & Ear Infirm, Dept Ophthalmol, 243 Charles St, Boston, MA 02114 USA. EM daniel_sun@meei.harvard.edu OI Jakobs, Tatjana/0000-0002-8104-9206 FU National Institutes of Health [RO1 017169, RO1 EY019703]; Glaucoma Foundation; American Health Assistance Foundation FX This work was supported by National Institutes of Health Grants RO1 017169 (R. H. M.) and RO1 EY019703 (T.C.J.) and by grants from The Glaucoma Foundation and the American Health Assistance Foundation (T.C.J.). NR 65 TC 39 Z9 40 U1 0 U2 5 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD OCT 20 PY 2010 VL 30 IS 42 BP 14008 EP 14019 DI 10.1523/JNEUROSCI.3605-10.2010 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 674YM UT WOS:000283788000011 PM 20962222 ER PT J AU Hancock, KE Noel, V Ryugo, DK Delgutte, B AF Hancock, Kenneth E. Noel, Victor Ryugo, David K. Delgutte, Bertrand TI Neural Coding of Interaural Time Differences with Bilateral Cochlear Implants: Effects of Congenital Deafness SO JOURNAL OF NEUROSCIENCE LA English DT Article ID AUDITORY BRAIN-STEM; ELECTRICAL-STIMULATION; INFERIOR COLLICULUS; SOUND LOCALIZATION; WHITE CATS; ULTRASTRUCTURAL ANALYSIS; BINAURAL INTERACTION; EVOKED-POTENTIALS; NERVE; SENSITIVITY AB Human bilateral cochlear implant users do poorly on tasks involving interaural time differences (ITD), a cue that provides important benefits to the normal hearing, especially in challenging acoustic environments, yet the precision of neural ITD coding in acutely deafened, bilaterally implanted cats is essentially normal (Smith and Delgutte, 2007a). One explanation for this discrepancy is that the extended periods of binaural deprivation typically experienced by cochlear implant users degrades neural ITD sensitivity, by either impeding normal maturation of the neural circuitry or altering it later in life. To test this hypothesis, we recorded from single units in inferior colliculus of two groups of bilaterally implanted, anesthetized cats that contrast maximally in binaural experience: acutely deafened cats, which had normal binaural hearing until experimentation, and congenitally deaf white cats, which received no auditory inputs until the experiment. Rate responses of only half as many neurons showed significant ITD sensitivity to low-rate pulse trains in congenitally deaf cats compared with acutely deafened cats. For neurons that were ITD sensitive, ITD tuning was broader and best ITDs were more variable in congenitally deaf cats, leading to poorer ITD coding within the naturally occurring range. A signal detection model constrained by the observed physiology supports the idea that the degraded neural ITD coding resulting from deprivation of binaural experience contributes to poor ITD discrimination by human implantees. C1 [Hancock, Kenneth E.; Delgutte, Bertrand] Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. [Noel, Victor] Massachusetts Eye & Ear Infirm, Cochlear Implant Res Lab, Boston, MA 02114 USA. [Hancock, Kenneth E.; Delgutte, Bertrand] Harvard Univ, Sch Med, Dept Otol & Laryngol, Boston, MA 02115 USA. [Ryugo, David K.] Johns Hopkins Univ, Dept Otolaryngol Head & Neck Surg, Sch Med, Baltimore, MD 21205 USA. [Delgutte, Bertrand] MIT, Elect Res Lab, Cambridge, MA 02139 USA. [Ryugo, David K.] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. RP Hancock, KE (reprint author), Massachusetts Eye & Ear Infirm, Eaton Peabody Lab, Boston, MA 02114 USA. EM Ken_Hancock@meei.harvard.edu RI Ryugo, David/G-1940-2012; OI Ryugo, David/0000-0002-5250-7503; , /0000-0003-1349-9608 FU National Institutes of Health [RO1 DC00575, RO1 DC00232, P30 DC005209]; Advanced Bionics Corporation FX This work was supported by National Institutes of Health Grants RO1 DC00575, RO1 DC00232, and P30 DC005209, and a grant from the Advanced Bionics Corporation. We are grateful to Connie Miller for surgical support and Melissa Wood for histological processing. NR 57 TC 31 Z9 31 U1 0 U2 6 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD OCT 20 PY 2010 VL 30 IS 42 BP 14068 EP 14079 DI 10.1523/JNEUROSCI.3213-10.2010 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 674YM UT WOS:000283788000017 PM 20962228 ER PT J AU Jena, AB AF Jena, Anupam B. TI Sexually Transmitted Diseases Among Users of Erectile Dysfunction Drugs RESPONSE SO ANNALS OF INTERNAL MEDICINE LA English DT Letter C1 Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Jena, AB (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD OCT 19 PY 2010 VL 153 IS 8 BP 550 EP 550 DI 10.7326/0003-4819-153-8-201010190-00021 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 665SA UT WOS:000283054600014 ER PT J AU Keyhani, S Woodward, M Federman, AD AF Keyhani, Salomeh Woodward, Mark Federman, Alex D. TI Physician Views on the Use of Comparative Effectiveness Research: A National Survey SO ANNALS OF INTERNAL MEDICINE LA English DT Letter C1 [Keyhani, Salomeh] James J Peters Vet Affairs Med Ctr, Bronx, NY 10468 USA. [Woodward, Mark] George Inst, Camperdown, NSW 2050, Australia. [Federman, Alex D.] Mt Sinai Sch Med, New York, NY 10029 USA. RP Keyhani, S (reprint author), James J Peters Vet Affairs Med Ctr, Bronx, NY 10468 USA. RI Woodward, Mark/D-8492-2015 NR 4 TC 6 Z9 7 U1 0 U2 1 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD OCT 19 PY 2010 VL 153 IS 8 BP 551 EP 552 DI 10.7326/0003-4819-153-8-201010190-00023 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 665SA UT WOS:000283054600016 PM 20956718 ER PT J AU Wilson, BG Wang, X Shen, XH McKenna, ES Lemieux, ME Cho, YJ Koellhoffer, EC Pomeroy, SL Orkin, SH Roberts, CWM AF Wilson, Boris G. Wang, Xi Shen, Xiaohua McKenna, Elizabeth S. Lemieux, Madeleine E. Cho, Yoon-Jae Koellhoffer, Edward C. Pomeroy, Scott L. Orkin, Stuart H. Roberts, Charles W. M. TI Epigenetic Antagonism between Polycomb and SWI/SNF Complexes during Oncogenic Transformation SO CANCER CELL LA English DT Article ID EMBRYONIC STEM-CELLS; TUMOR-SUPPRESSOR GENE; GROUP PROTEIN EZH2; RHABDOID TUMOR; DEVELOPMENTAL REGULATORS; GENOMIC INSTABILITY; SELF-RENEWAL; CANCER; CHROMATIN; DROSOPHILA AB Epigenetic alterations have been increasingly implicated in oncogenesis. Analysis of Drosophila mutants suggests that Polycomb and SWI/SNF complexes can serve antagonistic developmental roles. However, the relevance of this relationship to human disease is unclear. Here, we have investigated functional relationships between these epigenetic regulators in oncogenic transformation. Mechanistically, we show that loss of the SNF5 tumor suppressor leads to elevated expression of the Polycomb gene EZH2 and that Polycomb targets are broadly H3K27-trimethylated and repressed in SNF5-deficient fibroblasts and cancers. Further, we show antagonism between SNF5 and EZH2 in the regulation of stem cell-associated programs and that Snf5 loss activates those programs. Finally, using conditional mouse models, we show that inactivation of Ezh2 blocks tumor formation driven by Snf5 loss. C1 [Wilson, Boris G.; Wang, Xi; Shen, Xiaohua; McKenna, Elizabeth S.; Lemieux, Madeleine E.; Koellhoffer, Edward C.; Orkin, Stuart H.; Roberts, Charles W. M.] Harvard Univ, Div Hematol Oncol, Childrens Hosp Boston,Dept Pediat, Dept Pediat Oncol,Dana Farber Canc Inst,Sch Med, Boston, MA 02115 USA. [Cho, Yoon-Jae; Pomeroy, Scott L.] Childrens Hosp Boston, Dept Neurol, Boston, MA 02115 USA. [Orkin, Stuart H.] Howard Hughes Med Inst, Boston, MA 02115 USA. [Orkin, Stuart H.] Harvard Stem Cell Inst, Boston, MA 02115 USA. RP Roberts, CWM (reprint author), Harvard Univ, Div Hematol Oncol, Childrens Hosp Boston,Dept Pediat, Dept Pediat Oncol,Dana Farber Canc Inst,Sch Med, Boston, MA 02115 USA. EM charles_roberts@dfci.harvard.edu OI Koellhoffer, Edward/0000-0002-7260-9507; Lemieux, Madeleine/0000-0001-6355-8691 FU American Cancer Society [PF-07-261-01-DDC]; National Cancer Institute [1 F32 CA130312-01A1]; NCI Mouse Models of Cancer Consortium; PHS [R01CA113794]; Stand Up 2 Cancer; [R01 CA109467] FX Grant support was from the American Cancer Society New England Division-SpinOdyssey Postdoctoral Fellowship #PF-07-261-01-DDC from the American Cancer Society and the Ruth L. Kirschstein National Research Service Award Fellowship 1 F32 CA130312-01A1 from the National Cancer Institute (B.G.W.). This work was supported in part by a U01 NCI Mouse Models of Cancer Consortium Award (S.H.O. and C.W.M.R.) and a PHS award R01CA113794 (C.W.M.R.). C.W.M.R. is a recipient of an Innovative Research Grant from Stand Up 2 Cancer. The Garrett B. Smith Foundation, the Claudia Adams Barr Foundation, the Sarcoma Foundation of America (C.W.M.R.), and a R01 CA109467 research project grant (S.L.P.) provided additional support. S.H.O. is an Investigator of the HHMI. We thank Jen Perry for helpful discussions and permission to cite unpublished data. We also thank Pablo Tamayo for help with cross-platform analysis of microarray data, Pengcheng Zhou for isolation of murine cerebellum cells, and David James for the BT16 cell line. NR 50 TC 166 Z9 174 U1 1 U2 18 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 OCT 19 PY 2010 VL 18 IS 4 BP 316 EP 328 DI 10.1016/j.ccr.2010.09.006 PG 13 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 673XJ UT WOS:000283697200006 PM 20951942 ER PT J AU Feng, H Stachura, DL White, RM Gutierrez, A Zhang, L Sanda, T Jette, CA Testa, JR Neuberg, DS Langenau, DM Kutok, JL Zon, LI Traver, D Fleming, MD Kanki, JP Look, AT AF Feng, Hui Stachura, David L. White, Richard M. Gutierrez, Alejandro Zhang, Lu Sanda, Takaomi Jette, Cicely A. Testa, Joseph R. Neuberg, Donna S. Langenau, David M. Kutok, Jeffery L. Zon, Leonard I. Traver, David Fleming, Mark D. Kanki, John P. Look, A. Thomas TI T-Lymphoblastic Lymphoma Cells Express High Levels of BCL2, S1P1, and ICAM1, Leading to a Blockade of Tumor Cell Intravasation SO CANCER CELL LA English DT Article ID NON-HODGKIN-LYMPHOMA; C-MYC; SPHINGOSINE 1-PHOSPHATE; GENE-EXPRESSION; TRANSGENIC ZEBRAFISH; NOTCH1 MUTATIONS; LEUKEMIA; CHILDHOOD; CANCER; AUTOPHAGY AB The molecular events underlying the progression of T-lymphoblastic lymphoma (T-LBL) to acute T-lymphoblastic leukemia (T-ALL) remain elusive. In our zebrafish model, concomitant overexpression of bcl-2 with Myc accelerated T-LBL onset while inhibiting progression to T-ALL. The T-LBL cells failed to invade the vasculature and showed evidence of increased homotypic cell-cell adhesion and autophagy. Further analysis using clinical biopsy specimens revealed autophagy and increased levels of BCL2, S1P1, and ICAM1 in human T-LBL compared with T-ALL. Inhibition of S1P1 signaling in T-LBL cells led to decreased homotypic adhesion in vitro and increased tumor cell intravasation in vivo. Thus, blockade of intravasation and hematologic dissemination in T-LBL is due to elevated S1P1 signaling, increased expression of ICAM1, and augmented homotypic cell-cell adhesion. C1 [Feng, Hui; Gutierrez, Alejandro; Zhang, Lu; Sanda, Takaomi; Jette, Cicely A.; Kanki, John P.; Look, A. Thomas] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Stachura, David L.; Traver, David] Univ Calif San Diego, Cell & Dev Biol Sect, Dept Biol Sci, La Jolla, CA 92093 USA. [White, Richard M.; Gutierrez, Alejandro; Zon, Leonard I.; Look, A. Thomas] Childrens Hosp, Div Hematol Oncol, Boston, MA 02115 USA. [Testa, Joseph R.] Fox Chase Canc Ctr, Canc Biol Program, Philadelphia, PA 19111 USA. [Langenau, David M.] Massachusetts Gen Hosp, Dept Mol Pathol, Ctr Canc, Charlestown, MA 02129 USA. [Kutok, Jeffery L.] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. [Traver, David] Univ Calif Dan Diego Med Sch, Dept Cellular & Mol Med, La Jolla, CA 92093 USA. [Fleming, Mark D.] Childrens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Look, AT (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. EM thomas_look@dfci.harvard.edu OI Feng, Hui/0000-0003-1318-821X; Gutierrez, Alejandro/0000-0002-0249-9007 FU National Institutes of Health [CA068484, K99CA134743, NRSA T32-HL086344, 1K08CA133103, 1K01DK074555, CA077429, K01AR05562190-01A1, 3K01AR055619-03S1]; Leukemia & Lymphoma Society; Prevent Cancer Foundation; William Lawrence Foundation; Harvard Stem Cell Institute FX We thank M. Calicchio, Drs. L. Cameron, E. Payne, E. Breen, J. Struthers, G. Wei for technical help, advice, and reagents, J. Gilbert for editorial advice, and B. Baker and R. Gilbert and K.P. Kotredes for fish care and husbandry. This work was supported by grants from the National Institutes of Health (CA068484, A.T.L; K99CA134743, H.F.; NRSA T32-HL086344, D.L.S.; 1K08CA133103, A.G.; 1K01DK074555, C.A.J.; CA077429, J.R.T.; K01AR05562190-01A1 and 3K01AR055619-03S1, D.M.L.), the Leukemia & Lymphoma Society (H.F.), Prevent Cancer Foundation Postdoctoral Fellowship (D.L.S.), the William Lawrence Foundation (A.G.), and a Seed Grant from the Harvard Stem Cell Institute (D.M.L). L.I.Z. is a founder and stockholder of Fate, Inc. and a scientific advisor for Stemgent. A.T.L. is on the board of iLAB and a scientific advisor for OncoMed, Inc. The content of this research is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. NR 43 TC 69 Z9 70 U1 1 U2 9 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 OCT 19 PY 2010 VL 18 IS 4 BP 353 EP 366 DI 10.1016/j.ccr.2010.09.009 PG 14 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 673XJ UT WOS:000283697200009 PM 20951945 ER PT J AU Poole, JE Gleva, MJ Mela, T Chung, MK Uslan, DZ Borge, R Gottipaty, V Shinn, T Dan, D Feldman, LA Seide, H Winston, SA Gallagher, JJ Langberg, JJ Mitchell, K Holcomb, R AF Poole, Jeanne E. Gleva, Marye J. Mela, Theofanie Chung, Mina K. Uslan, Daniel Z. Borge, Richard Gottipaty, Venkateshwar Shinn, Timothy Dan, Dan Feldman, Leon A. Seide, Hanscy Winston, Stuart A. Gallagher, John J. Langberg, Jonathan J. Mitchell, Kevin Holcomb, Richard CA REPLACE Registry Investigators TI Complication Rates Associated With Pacemaker or Implantable Cardioverter-Defibrillator Generator Replacements and Upgrade Procedures Results From the REPLACE Registry SO CIRCULATION LA English DT Article DE complications; electrophysiology; implantable cardioverter defibrillators; pacemakers ID CONGESTIVE-HEART-FAILURE; PERMANENT PACEMAKER; SINGLE-CHAMBER; DUAL-CHAMBER; CARDIAC-RESYNCHRONIZATION; DEVICE ADVISORIES; LEAD; RISK; AMIODARONE; MORBIDITY AB Background-Prospective studies defining the risk associated with pacemaker or implantable cardioverter-defibrillator replacement surgeries do not exist. These procedures are generally considered low risk despite results from recent retrospective series reporting higher rates. Methods and Results-We prospectively assessed predefined procedure-related complication rates associated with elective pacemaker or implantable cardioverter-defibrillator generator replacements over 6 months of follow-up. Two groups were studied: those without (cohort 1) and those with (cohort 2) a planned transvenous lead addition for replacement or upgrade to a device capable of additional therapies. Complications were adjudicated by an independent events committee. Seventy-two US academic and private practice centers participated. Major complications occurred in 4.0% (95% confidence interval, 2.9 to 5.4) of 1031 cohort 1 patients and 15.3% (95% confidence interval, 12.7 to 18.1) of 713 cohort 2 patients. In both cohorts, major complications were higher with implantable cardioverter-defibrillator compared with pacemaker generator replacements. Complications were highest in patients who had an upgrade to or a revised cardiac resynchronization therapy device (18.7%; 95% confidence interval, 15.1 to 22.6). No periprocedural deaths occurred in either cohort, although 8 later procedure-related deaths occurred in cohort 2. The 6-month infection rates were 1.4% (95% confidence interval, 0.7 to 2.3) and 1.1% (95% confidence interval, 0.5 to 2.2) for cohorts 1 and 2, respectively. Conclusions-Pacemaker and implantable cardioverter-defibrillator generator replacements are associated with a notable complication risk, particularly those with lead additions. These data support careful decision making before device replacement, when managing device advisories, and when considering upgrades to more complex systems. C1 [Poole, Jeanne E.] Univ Washington, Div Cardiol, Seattle, WA 98198 USA. [Gleva, Marye J.] Washington Univ, Sch Med, St Louis, MO USA. [Mela, Theofanie] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Chung, Mina K.] Cleveland Clin, Cleveland, OH 44106 USA. [Uslan, Daniel Z.] Univ Calif Los Angeles, Los Angeles, CA 90024 USA. [Borge, Richard] Abington Med Specialists, Abington, PA USA. [Gottipaty, Venkateshwar] S Carolina Heart Ctr, Columbia, SC USA. [Shinn, Timothy; Winston, Stuart A.] Michigan Heart, Ypsilanti, MI USA. [Dan, Dan] Piedmont Heart Inst, Atlanta, GA USA. [Feldman, Leon A.] Desert Cardiol, Rancho Mirage, CA USA. [Seide, Hanscy] Halifax Med Ctr, Daytona Beach, FL USA. [Gallagher, John J.] Spartanburg Reg, Spartanburg, SC USA. [Langberg, Jonathan J.] Emory Univ, Atlanta, GA 30322 USA. [Mitchell, Kevin] BIOTRONIK Inc, Lake Oswego, OR USA. RP Poole, JE (reprint author), Univ Washington, Div Cardiol, 1959 NE Pacific St,Box 356422, Seattle, WA 98198 USA. EM jpoole@u.washington.edu RI Library, Woodruff Health/A-6096-2012 FU BIOTRONIK, Inc.; National Heart, Lung, and Blood Institute; Medtronic; Boston Scientific; St. Jude Medical; American Heart Association; Tyrx; Sonofi-Aventis; BIOTRONIK FX The REPLACE Registry was sponsored and funded by BIOTRONIK, Inc. Study participants from the sponsor contributed to the trial design and study process but were blinded to the clinical data and complication end points until after final data analysis of each cohort.; Dr Poole reports receiving research grant support from BIOTRONIK and the National Heart, Lung, and Blood Institute; speaking honoraria from Medtronic and Boston Scientific; travel reimbursement from BIOTRONIK, Medtronic, and Boston Scientific; and honoraria from Cardiac Science. Dr Poole has been an expert witness. Dr Poole also reports fellowship training grants to her institution from Medtronic, Boston Scientific, and St. Jude Medical. Dr Gleva has received research support from BIOTRONIK, honoraria from Medtronic and BIOTRONIK, and travel reimbursement from BIOTRONIK; Dr Gleva's spouse has ownership stock in Medtronic. Dr Mela reports speaking honoraria, advisory board, and travel reimbursement from BIOTRONIK. Dr Chung reports research grants from Medtronic, Boston Scientific, St. Jude Medical, and BIOTRONIK, as well as travel reimbursement from BIOTRONIK, St. Jude Medical, Medtronic, and Boston Scientific. Dr Uslan has received research grants from the American Heart Association, honoraria from BIOTRONIK, consulting fees from Tyrx, travel reimbursement from BIOTRONIK, and fees for participation in study review activities from BIOTRONIK. Dr Borge reports speakers' bureau honoraria from BIOTRONIK, Boston Scientific, St. Jude Medical, and Sanofi-Aventis, as well as a consultancy with Medtronic and travel reimbursement from BIOTRONIK. Dr Gottipaty has received honoraria from BIOTRONIK, St. Jude Medical, Boston Scientific, Medtronic, and Sanofi-Aventis and travel reimbursement from BIOTRONIK. Dr Shinn has received research grants from Boston Scientific, Medtonic, Sonofi-Aventis, and BIOTRONIK; travel reimbursement from BIOTRONIK; speaker's fees from BIOTRONIK; and honoraria from Medtronic. Dr Shinn has a consultancy with Medtronic and BIOTRONIK and has been an expert witness; his brother-in-law is a Medtronic employee. Dr Dan has received speaker fees from Boston Scientific, Medtronic, and Sorin; honoraria from Boston Scientific, Medtronic, St. Jude Medical, Sorin, and Sanofi-Aventis; and travel reimbursement from BIOTRONIK. Dr Dan also has a consultancy with BIOTRONIK, Boston Scientific, and Sorin. Dr Feldman reports that his institution has received research support from Medtronic, Boston Scientific, St. Jude Medical, and BIOTRONIK. Dr Feldman receives speakers' bureau fees from Medtronic and Boston Scientific and receives travel reimbursement from and has a consultancy with Boston Scientific and BIOTRONIK. Dr Winston reports research grants from Medtronic, Boston Scientific, St. Jude Medical, and BIOTRONIK to his institution and receives honoraria from St. Jude Medical, Boston Scientific, and BIOTRONIK. Dr Langberg reports that his institution receives research support from BIOTRONIK. K. Mitchell is a paid employee of BIOTRONIK and receives a fixed salary with no bonus payments tied to research results. Dr Holcomb has received consulting fees from BIOTRONIK to perform the statistical analysis for the study. In addition to the individual disclosures noted above, the institutions of several authors (Drs Poole, Gleva, Mela, Chung, Borge, Gottipaty, Shinn, Winston, Dan, Feldman, Seide, Gallagher, and Langberg) participated as an enrolling site in REPLACE and received research support from BIOTRONIK for the conduct of the trial. Drs Seide and Gallagher report no conflicts. NR 31 TC 205 Z9 207 U1 4 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 19 PY 2010 VL 122 IS 16 BP 1553 EP U43 DI 10.1161/CIRCULATIONAHA.110.976076 PG 11 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 667LY UT WOS:000283196000008 PM 20921437 ER PT J AU Correa, D Hesse, E Seriwatanachai, D Kiviranta, R Saito, H Yamana, K Neff, L Atfi, A Coillard, L Sitara, D Maeda, Y Warming, S Jenkins, NA Copeland, NG Horne, WC Lanske, B Baron, R AF Correa, Diego Hesse, Eric Seriwatanachai, Dutmanee Kiviranta, Riku Saito, Hiroaki Yamana, Kei Neff, Lynn Atfi, Azeddine Coillard, Lucie Sitara, Despina Maeda, Yukiko Warming, Soren Jenkins, Nancy A. Copeland, Neal G. Horne, William C. Lanske, Beate Baron, Roland TI Zfp521 Is a Target Gene and Key Effector of Parathyroid Hormone-Related Peptide Signaling in Growth Plate Chondrocytes SO DEVELOPMENTAL CELL LA English DT Article ID ZINC-FINGER PROTEIN; ENDOCHONDRAL BONE-FORMATION; INDIAN HEDGEHOG; OSTEOBLAST DIFFERENTIATION; RETROVIRAL INTEGRATION; CBFA1-DEFICIENT MICE; HISTONE DEACETYLASES; SKELETAL DEVELOPMENT; RUNX2 EXPRESSION; TGF-BETA AB In the growth plate, the interplay between parathyroid hormone-related peptide (PTHrP) and Indian hedgehog (Ihh) signaling tightly regulates chondrocyte proliferation and differentiation during longitudinal bone growth. We found that PTHrP increases the expression of Zfp521, a zinc finger transcriptional coregulator, in prehypertrophic chondrocytes. Mice with chondrocyte-targeted deletion of Zfp521 resembled PTHrP(-/-) and chondrocyte-specific PTHR1(-/-) mice, with decreased chondrocyte proliferation, early hypertrophic transition, and reduced growth plate thickness. Deleting Zfp521 increased expression of Runx2 and Runx2 target genes, and decreased Cyclin D1 and BcI-2 expression while increasing Caspase-3 activation and apoptosis. Zfp521 associated with Runx2 in chondrocytes, antagonizing its activity via an HDAC4-dependent mechanism. PTHrP failed to upregulate Cyclin D1 and to antagonize Runx2, Ihh, and collagen X expression when Zfp521 was absent. Thus, Zfp521 is an important PTHrP target gene that regulates growth plate chondrocyte proliferation and differentiation. C1 [Correa, Diego; Hesse, Eric; Kiviranta, Riku; Saito, Hiroaki; Yamana, Kei; Neff, Lynn; Atfi, Azeddine; Coillard, Lucie; Horne, William C.; Baron, Roland] Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, Boston, MA 02115 USA. [Seriwatanachai, Dutmanee; Sitara, Despina; Maeda, Yukiko; Lanske, Beate] Harvard Univ, Sch Dent Med, Dept Dev Biol, Boston, MA 02115 USA. [Yamana, Kei] Teijin Pharma Ltd, Teijin Inst Biomed Res, Tokyo 1918512, Japan. [Warming, Soren] Genentech Inc, Mol Biol, San Francisco, CA 94080 USA. [Jenkins, Nancy A.; Copeland, Neal G.] Inst Mol & Cell Biol, Canc Genet Lab, Singapore 138673, Singapore. [Baron, Roland] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Endocrine Unit, Boston, MA 02114 USA. RP Baron, R (reprint author), Harvard Univ, Sch Dent Med, Dept Oral Med Infect & Immun, 188 Longwood Ave, Boston, MA 02115 USA. EM roland_baron@hsdm.harvard.edu RI ASTAR, IMCB/E-2320-2012; OI SITARA, DESPINA/0000-0002-4836-5039 FU National Institutes of Health-NIAMS [AR048218, AR050560]; NIH [GM07527]; Gustavus and Louise Pfeiffer Research Foundation; Deutsche Forschungsgemeinschaft [HE 5208/1-1]; International Bone and Mineral Society; Academy of Finland FX We thank Dr. B. Lee for MCT cells, Dr. E. Schipani for the PTHR1 - HKrk-H223R transgenic mice, Dr. A. Broadus for the PTHrP-/- mice, Dr. A. Lassar for HDAC4 and GAPDH siRNA plasmids, Dr. F. Long for the Col II-Cre mice, and Dr. H. Kronenberg for helpful discussion. Support was provided in part by National Institutes of Health-NIAMS grants AR048218 (R.B.) and AR050560 (B.L.). Additional support was provided by NIH training grant GM07527 (D.C.), the George Robert Pfeiffer Fellowship from the Gustavus and Louise Pfeiffer Research Foundation (D.C.), the Deutsche Forschungsgemeinschaft (E.H., HE 5208/1-1), the Gideon & Sevgi Rodan Fellowship from the International Bone and Mineral Society (E.H. and R.K.), the Academy of Finland (R.K.), and the Harvard School of Dental Medicine Dean's Scholars Award (E.H.). NR 48 TC 41 Z9 41 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD OCT 19 PY 2010 VL 19 IS 4 BP 533 EP 546 DI 10.1016/j.devcel.2010.09.008 PG 14 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 671QM UT WOS:000283522700007 PM 20951345 ER PT J AU Rich, JD Cannon, CP Murphy, SA Qin, J Giugliano, RP Braunwald, E AF Rich, Jonathan D. Cannon, Christopher P. Murphy, Sabina A. Qin, Jie Giugliano, Robert P. Braunwald, Eugene TI Prior Aspirin Use and Outcomes in Acute Coronary Syndromes SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article DE acute coronary syndromes; aspirin; myocardial infarction; prognosis; risk factors ID ACUTE MYOCARDIAL-INFARCTION; TISSUE-PLASMINOGEN-ACTIVATOR; ST-SEGMENT ELEVATION; TIMI RISK SCORE; UNSTABLE ANGINA; CONSERVATIVE STRATEGIES; UNFRACTIONATED HEPARIN; ANTIPLATELET THERAPY; RANDOMIZED TRIALS; INTRAVENOUS NPA AB Objectives The purpose of this study was to determine whether patients taking aspirin before an acute coronary syndrome (ACS) are at higher risk of recurrent events or mortality. Background Controversy exists whether prior aspirin use is an independent predictor of worse outcomes in patients who experience an ACS. Methods We evaluated 66,443 ACS patients from a merged database of previous Thrombolysis in Myocardial Infarction trials. We evaluated the differences in ACS type, total mortality, and the composite end point of death, myocardial infarction (MI), recurrent ischemia, or stroke between prior aspirin and nonprior aspirin users. We used multivariate analysis to control for differences in baseline characteristics. Results Prior aspirin users (n = 17,839) were older (63 years vs. 59 years) and had more coronary risk factors and evidence of coronary artery disease (MI, angina, prior intervention) than nonprior aspirin users (n = 48,604) (all p < 0.0001). Prior aspirin use was associated with less severe types of ACS at presentation (e.g., unstable angina > non-ST-segment elevation MI > ST-segment elevation MI) than their nonaspirin user counterparts (p < 0.0001). After multivariate analysis, there was no difference in total mortality between prior aspirin users and nonaspirin users at day 30 (odds ratio [OR]: 1.01; 95% confidence interval [CI]: 0.90 to 1.13) or by the last follow-up visit (mean 328 days) (hazard ratio: 1.03; 95% CI: 0.95 to 1.11). Prior aspirin use was modestly associated with recurrent MI (OR: 1.26; 95% CI: 1.12 to 1.43) and the composite end point (OR: 1.16; 95% CI: 1.08 to 1.24). Conclusions Prior aspirin use was associated with more comorbidities and coronary disease and a higher risk of recurrent MI, but not mortality. As such, it should best be considered a marker of a patient population at high risk for recurrent adverse events after ACS. (J Am Coll Cardiol 2010;56:1376-85) (C) 2010 by the American College of Cardiology Foundation C1 [Cannon, Christopher P.; Murphy, Sabina A.; Qin, Jie; Giugliano, Robert P.; Braunwald, Eugene] Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc, Boston, MA 02115 USA. [Cannon, Christopher P.; Murphy, Sabina A.; Qin, Jie; Giugliano, Robert P.; Braunwald, Eugene] Harvard Univ, Sch Med, Boston, MA USA. [Rich, Jonathan D.] Univ Chicago, Dept Med, Cardiol Sect, Chicago, IL 60637 USA. RP Cannon, CP (reprint author), Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA. EM cpcannon@partners.org RI bashzar, salman/R-5748-2016 FU Accumetrics; AstraZeneca; GlaxoSmithKline; Intekrin Therapeutics; Merck; Takeda; Johnson Johnson; Beckman Coulter Inc.; Eli Lilly; Genentech; Integrated Therapeutics Group; Merck Co. Inc.; Novartis; Roche Diagnostics Corp.; Sanofi Aventis; Daiichi Sankyo FX the TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. Dr. Cannon has received research grants/support from Accumetrics, AstraZeneca, GlaxoSmithKline, Intekrin Therapeutics, Merck, and Takeda; is on the advisory board for Bristol-Myers Squibb/Sanofi, Novartis, and Alnylam; and is a clinical advisor with equity Automedics Medical Systems. Jie Qin is an employee of Biostatistics China, Sanofi Pasteur. Dr. Braunwald is Chairman of the TIMI Study Group who has received grant support from AstraZeneca, Johnson & Johnson, Beckman Coulter Inc., Eli Lilly, Genentech, Integrated Therapeutics Group, Merck & Co. Inc., Novartis, Roche Diagnostics Corp., Sanofi Aventis, Daiichi Sankyo, and GlaxoSmithKline; and has received honorarium from Daiichi Sankyo, Eli Lilly, Merck & Co., and Genzyme. All other authors have reported that they have no relationships to disclose. NR 42 TC 22 Z9 22 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD OCT 19 PY 2010 VL 56 IS 17 BP 1376 EP 1385 DI 10.1016/j.jacc.2010.06.028 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 662QV UT WOS:000282827300004 PM 20946994 ER PT J AU Burton, DR AF Burton, Dennis R. TI Scaffolding to build a rational vaccine design strategy SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Editorial Material ID IMMUNODEFICIENCY-VIRUS TYPE-1; COMPLEMENTARITY-DETERMINING REGION; PROXIMAL EXTERNAL REGION; ANTIBODY 2F5; MONOCLONAL-ANTIBODY; HEAVY-CHAIN; GP41; EPITOPE; HIV-1; AUTOREACTIVITY C1 [Burton, Dennis R.] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA. [Burton, Dennis R.] Scripps Res Inst, Int AIDS Vaccine Initiat Neutralizing Antibody Ct, La Jolla, CA 92037 USA. [Burton, Dennis R.] Massachusetts Gen Hosp, Ragon Inst, MIT, Boston, MA 02114 USA. [Burton, Dennis R.] Harvard Univ, Boston, MA 02114 USA. RP Burton, DR (reprint author), Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA. EM burton@scripps.edu NR 21 TC 29 Z9 29 U1 0 U2 7 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 19 PY 2010 VL 107 IS 42 BP 17859 EP 17860 DI 10.1073/pnas.1012923107 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 667HV UT WOS:000283184800005 PM 20937874 ER PT J AU Fan, XC Moqtaderi, Z Jin, Y Zhang, Y Liu, XS Struhl, K AF Fan, Xiaochun Moqtaderi, Zarmik Jin, Yi Zhang, Yong Liu, X. Shirley Struhl, Kevin TI Nucleosome depletion at yeast terminators is not intrinsic and can occur by a transcriptional mechanism linked to 3 '-end formation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE nucleosome positioning; chromatin structure; genome organization ID HISTONE-DNA INTERACTIONS; RNA-POLYMERASE-II; IN-VIVO; PREFERENTIAL ACCESSIBILITY; SACCHAROMYCES-CEREVISIAE; EUKARYOTIC GENOME; HIGH-RESOLUTION; PROMOTER; SEQUENCE; ELONGATION AB Genome-wide mapping of nucleosomes generated by micrococcal nuclease (MNase) suggests that yeast promoter and terminator regions are very depleted of nucleosomes, predominantly because their DNA sequences intrinsically disfavor nucleosome formation. However, MNase has strong DNA sequence specificity that favors cleavage at promoters and terminators and accounts for some of the correlation between occupancy patterns of nucleosomes assembled in vivo and in vitro. Using an improved method for measuring nucleosome occupancy in vivo that does not involve MNase, we confirm that promoter regions are strongly depleted of nucleosomes, but find that terminator regions are much less depleted than expected. Unlike at promoter regions, nucleosome occupancy at terminators is strongly correlated with the orientation of and distance to adjacent genes. In addition, nucleosome occupancy at terminators is strongly affected by growth conditions, indicating that it is not primarily determined by intrinsic histone-DNA interactions. Rapid removal of RNA polymerase II (pol II) causes increased nucleosome occupancy at terminators, strongly suggesting a transcription-based mechanism of nucleosome depletion. However, the distinct behavior of terminator regions and their corresponding coding regions suggests that nucleosome depletion at terminators is not simply associated with passage of pol II, but rather involves a distinct mechanism linked to 3'-end formation. C1 [Fan, Xiaochun; Moqtaderi, Zarmik; Jin, Yi; Struhl, Kevin] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Zhang, Yong; Liu, X. Shirley] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA. [Zhang, Yong] Tongji Univ, Sch Life Sci & Technol, Shanghai 200092, Peoples R China. RP Struhl, K (reprint author), Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. EM kevin@hms.harvard.edu RI Zhang, Yong/B-4838-2011; Jin, Yi/I-7234-2012 OI Zhang, Yong/0000-0001-6316-2734; FU National Basic Research Program of China (973 Program) [2010CB944904]; National Institutes of Health [HG4069, GM30186] FX We thank Y. Chen and T. Liu for help with the MAT analysis. This work was supported by grants from the National Basic Research Program of China (973 Program) 2010CB944904 (to Y.Z.) and from the National Institutes of Health, HG4069 (to X.S.L.) and GM30186 (to K.S.). NR 35 TC 42 Z9 42 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 19 PY 2010 VL 107 IS 42 BP 17945 EP 17950 DI 10.1073/pnas.1012674107 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 667HV UT WOS:000283184800021 PM 20921369 ER PT J AU Veiga, P Gallini, CA Beal, C Michaud, M Delaney, ML DuBois, A Khlebnikov, A Vlieg, JETV Punit, S Glickman, JN Onderdonk, A Glimcher, LH Garrett, WS AF Veiga, Patrick Gallini, Carey Ann Beal, Chloe Michaud, Monia Delaney, Mary L. DuBois, Andrea Khlebnikov, Artem Vlieg, Johan E. T. van Hylckama Punit, Shivesh Glickman, Jonathan N. Onderdonk, Andrew Glimcher, Laurie H. Garrett, Wendy S. TI Bifidobacterium animalis subsp lactis fermented milk product reduces inflammation by altering a niche for colitogenic microbes SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE Enterobacteriaceae; intestinal inflammation; microbiota; probiotics; colitis ID GUT MICROBIOTA; ESCHERICHIA-COLI; BOWEL-DISEASE; FECAL MICROBIOTA; COLONIC-MUCOSA; ORGANIC-ACIDS; PROBIOTICS; SALMONELLA; BACTERIA; SYSTEM AB Intestinal health requires the coexistence of eukaryotic self with the gut microbiota and dysregulated host-microbial interactions can result in intestinal inflammation. Here, we show that colitis improved in T-bet(-/-)Rag2(-/-) mice that consumed a fermented milk product containing Bifidobacterium animalis subsp. lactis DN-173 010 strain. A decrease in cecal pH and alterations in short chain fatty acid profiles occurred with consumption, and there were concomitant increases in the abundance of select lactate-consuming and butyrate-producing bacteria. These metabolic shifts created a nonpermissive environment for the Enterobacteriaceae recently identified as colitogenic in a T-bet(-/-)Rag2(-/-) ulcerative colitis mouse model. In addition, 16S rRNA-based analysis of the T-bet(-/-)Rag2(-/-) fecal microbiota suggest that the structure of the endogenous gut microbiota played a key role in shaping the host response to the bacterial strains studied herein. We have identified features of the gut microbiota, at the membership and functional level, associated with response to this B. lactis-containing fermented milk product, and therefore this model provides a framework for evaluating and optimizing probiotic-based functional foods. C1 [Veiga, Patrick; Gallini, Carey Ann; Michaud, Monia; Punit, Shivesh; Glimcher, Laurie H.; Garrett, Wendy S.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Veiga, Patrick; Beal, Chloe; Khlebnikov, Artem; Vlieg, Johan E. T. van Hylckama] Danone Res, F-91767 Palaiseau, France. [Delaney, Mary L.; DuBois, Andrea; Glickman, Jonathan N.; Onderdonk, Andrew] Brigham & Womens Hosp, Boston, MA 02115 USA. [Khlebnikov, Artem; Glimcher, Laurie H.] Dannon Co Inc, White Plains, NY 10603 USA. [Glickman, Jonathan N.; Onderdonk, Andrew; Glimcher, Laurie H.; Garrett, Wendy S.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Glimcher, Laurie H.] MIT, Ragon Inst MGH, Charlestown, MA 02129 USA. Harvard Univ, Charlestown, MA 02129 USA. [Garrett, Wendy S.] Dana Farber Canc Inst, Boston, MA 02115 USA. RP Garrett, WS (reprint author), Harvard Univ, Sch Publ Hlth, 665 Huntington Ave, Boston, MA 02115 USA. EM wgarrett@hsph.harvard.edu RI Veiga, Patrick/A-9862-2011; Khlebnikov, Artem/K-4780-2012; van Hylckama Vlieg, Johan/F-7887-2014; Beal, Chloe/N-1992-2014 OI Veiga, Patrick/0000-0001-6318-8547; Khlebnikov, Artem/0000-0002-1866-234X; van Hylckama Vlieg, Johan/0000-0001-6656-8668; Beal, Chloe/0000-0002-4154-4720 FU National Institutes of Health [CA112663, K08AIO78942]; Danone Research FX We thank D. Zhang for histology expertise and M. Montesalvo and staff of the University of Massachusetts Lowell Radiation Laboratory for use of their Gamma Cave Irradiator Facility. This work was supported by National Institutes of Health Grants CA112663 (to L.H.G.) and K08AIO78942 (to W.S.G.) and by a grant from Danone Research. NR 46 TC 91 Z9 94 U1 1 U2 31 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 19 PY 2010 VL 107 IS 42 BP 18132 EP 18137 DI 10.1073/pnas.1011737107 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 667HV UT WOS:000283184800053 PM 20921388 ER PT J AU Srikanth, CV Wall, DM Maldonado-Contreras, A Shi, HN Zhou, DG Demma, Z Mumy, KL McCormick, BA AF Srikanth, C. V. Wall, Daniel M. Maldonado-Contreras, Ana Shi, Hai Ning Zhou, Daoguo Demma, Zachary Mumy, Karen L. McCormick, Beth A. TI Salmonella Pathogenesis and Processing of Secreted Effectors by Caspase-3 SO SCIENCE SIGNALING LA English DT Editorial Material ID EPITHELIAL-CELLS; TYPHIMURIUM; PROTEIN; ACTIN; INVASION; IDENTIFICATION; FILAMENTS; ABILITY; GROWTH; DOMAIN AB The enteric pathogen Salmonella enterica serovar Typhimurium causes food poisoning resulting in gastroenteritis. The S. Typhimurium effector Salmonella invasion protein A (SipA) promotes gastroenteritis by functional motifs that trigger either mechanisms of inflammation or bacterial entry. During infection of intestinal epithelial cells, SipA was found to be responsible for the early activation of caspase-3, an enzyme that is required for SipA cleavage at a specific recognition motif that divided the protein into its two functional domains and activated SipA in a manner necessary for pathogenicity. Other caspase-3 cleavage sites identified in S. Typhimurium appeared to be restricted to secreted effector proteins, which indicates that this may be a general strategy used by this pathogen for processing of its secreted effectors. C1 [Srikanth, C. V.; Wall, Daniel M.; Shi, Hai Ning; Mumy, Karen L.; McCormick, Beth A.] Harvard Univ, Sch Med, Dept Pediat Gastroenterol & Nutr, Boston, MA 02129 USA. [Srikanth, C. V.; Wall, Daniel M.; Shi, Hai Ning; Mumy, Karen L.; McCormick, Beth A.] Massachusetts Gen Hosp, Boston, MA 02129 USA. [Srikanth, C. V.; Maldonado-Contreras, Ana; Demma, Zachary; Mumy, Karen L.; McCormick, Beth A.] Univ Massachusetts, Sch Med, Dept Mol Genet & Microbiol, Worcester, MA 01655 USA. [Wall, Daniel M.] Univ Glasgow, Inst Infect Immun & Inflammat, Coll Med Vet & Life Sci, Glasgow G12 8QQ, Lanark, Scotland. [Zhou, Daoguo] Purdue Univ, Dept Biol Sci, W Lafayette, IN 47907 USA. RP McCormick, BA (reprint author), Harvard Univ, Sch Med, Dept Pediat Gastroenterol & Nutr, Boston, MA 02129 USA. EM Beth.McCormick@umassmed.edu FU NIH [DK56754, DK33506]; Crohn's and Colitis Foundation of America; Tenovus Scotland; Society for General Microbiology FX The research was supported by grants from the NIH (DK56754 and DK33506) and the Crohn's and Colitis Foundation of America to B. A. M. Additional grant support was provided by Tenovus Scotland and a Society for General Microbiology travel award to D. M. W. The use of human volunteers in this study was in accordance with appropriate guidelines and was approved by the University of Massachusetts Medical School Review Board for the Protection of Human Subjects (approval no. 13006). NR 22 TC 0 Z9 0 U1 1 U2 8 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1937-9145 J9 SCI SIGNAL JI Sci. Signal. PD OCT 19 PY 2010 VL 3 IS 144 PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 667EJ UT WOS:000283175200007 ER PT J AU Jelluma, N Dansen, TB Sliedrecht, T Kwiatkowski, NP Kops, GJPL AF Jelluma, Nannette Dansen, Tobias B. Sliedrecht, Tale Kwiatkowski, Nicholas P. Kops, Geert J. P. L. TI Release of Mps1 from kinetochores is crucial for timely anaphase onset SO JOURNAL OF CELL BIOLOGY LA English DT Article ID SPINDLE-ASSEMBLY CHECKPOINT; MITOTIC CHECKPOINT; AURORA-B; CENP-E; MICROTUBULE ATTACHMENT; CENTROSOME DUPLICATION; CHROMOSOME ALIGNMENT; OUTER KINETOCHORE; KINASE-ACTIVITY; CANCER-CELLS AB Mps1 kinase activity is required for proper chromosome segregation during mitosis through its involvements in microtubule-chromosome attachment error correction and the mitotic checkpoint. Mps1 dynamically exchanges on unattached kinetochores but is largely removed from kinetochores in metaphase. Here we show that Mps1 promotes its own turnover at kinetochores and that removal of Mps1 upon chromosome biorientation is a prerequisite for mitotic checkpoint silencing. Inhibition of Mps1 activity increases its half-time of recovery at unattached kinetochores and causes accumulation of Mps1 protein at these sites Strikingly, preventing dissociation of active Mps1 from kinetochores delays anaphase onset despite normal chromosome attachment and alignment, and high interkinetochore tension. This delay is marked by continued recruitment of Mad1 and Mad2 to bioriented chromosomes and is attenuated by Mad2 depletion, indicating chronic engagement of the mitotic checkpoint in metaphase. We propose that release of Mps1 from kinetochores is essential for mitotic checkpoint silencing and a fast metaphase-to-anaphase transition C1 [Jelluma, Nannette; Dansen, Tobias B.; Sliedrecht, Tale; Kops, Geert J. P. L.] UMC Utrecht, Dept Physiol Chem, NL-3584 CG Utrecht, Netherlands. [Jelluma, Nannette; Dansen, Tobias B.; Sliedrecht, Tale; Kops, Geert J. P. L.] UMC Utrecht, Canc Genom Ctr, NL-3584 CG Utrecht, Netherlands. [Sliedrecht, Tale; Kops, Geert J. P. L.] Netherlands Prote Ctr, Utrecht, Netherlands. [Kwiatkowski, Nicholas P.] Harvard Univ, Dept Biol Chem & Mol Pharmacol, Dept Canc Biol, Dana Farber Canc Inst,Sch Med, Boston, MA 02115 USA. RP Kops, GJPL (reprint author), UMC Utrecht, Dept Physiol Chem, NL-3584 CG Utrecht, Netherlands. OI Kops, Geert/0000-0003-3555-5295 FU Netherlands Organization for Scientific Research [NWO-91776336]; ERC; Netherlands Genomics Initiative FX This work was supported by a VIDI grant of the Netherlands Organization for Scientific Research (NWO-91776336), an ERC Starting Independent Researcher Grant (KINSIGN) to G.J.P.L. Kops, and by the Netherlands Genomics Initiative. NR 46 TC 55 Z9 56 U1 0 U2 5 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD OCT 18 PY 2010 VL 191 IS 2 BP 281 EP 290 DI 10.1083/jcb.201003038 PG 10 WC Cell Biology SC Cell Biology GA 670AH UT WOS:000283391500009 PM 20937696 ER PT J AU Baek, RC Broekman, MLD Leroy, SG Tierney, LA Sandberg, MA d'Azzo, A Seyfried, TN Sena-Esteves, M AF Baek, Rena C. Broekman, Marike L. D. Leroy, Stanley G. Tierney, Laryssa A. Sandberg, Michael A. d'Azzo, Alessandra Seyfried, Thomas N. Sena-Esteves, Miguel TI AAV-Mediated Gene Delivery in Adult GM1-Gangliosidosis Mice Corrects Lysosomal Storage in CNS and Improves Survival SO PLOS ONE LA English DT Article ID ACID BETA-GALACTOSIDASE; SANDHOFF-DISEASE MICE; GM1 GANGLIOSIDOSIS; MOUSE MODEL; ANIMAL-MODEL; NIEMANN-PICK; GENERALIZED GANGLIOSIDOSIS; BRAIN GANGLIOSIDE; RAT-BRAIN; THERAPY AB Background: GM1-gangliosidosis is a glycosphingolipid (GSL) lysosomal storage disease caused by a genetic deficiency of acid beta-galactosidase (beta gal), which results in the accumulation of GM1-ganglioside and its asialo-form (GA1) primarily in the CNS. Age of onset ranges from infancy to adulthood, and excessive ganglioside accumulation produces progressive neurodegeneration and psychomotor retardation in humans. Currently, there are no effective therapies for the treatment of GM1-gangliosidosis. Methodology/Principal Findings: In this study we examined the effect of thalamic infusion of AAV2/1-beta gal vector in adult GM1 mice on enzyme distribution, activity, and GSL content in the CNS, motor behavior, and survival. Six to eight week-old GM1 mice received bilateral injections of AAV vector in the thalamus, or thalamus and deep cerebellar nuclei (DCN) with pre-determined endpoints at 1 and 4 months post-injection, and the humane endpoint, or 52 weeks of age. Enzyme activity was elevated throughout the CNS of AAV-treated GM1 mice and GSL storage nearly normalized in most structures analyzed, except in the spinal cord which showed similar to 50% reduction compared to age-matched untreated GM1 mice spinal cord. Survival was significantly longer in AAV-treated GM1 mice (52 wks) than in untreated mice. However the motor performance of AAV-treated GM1 mice declined over time at a rate similar to that observed in untreated GM1 mice. Conclusions/Significance: Our studies show that the AAV-modified thalamus can be used as a 'built-in' central node network for widespread distribution of lysosomal enzymes in the mouse cerebrum. In addition, this study indicates that thalamic delivery of AAV vectors should be combined with additional targets to supply the cerebellum and spinal cord with therapeutic levels of enzyme necessary to achieve complete correction of the neurological phenotype in GM1 mice. C1 [Baek, Rena C.; Seyfried, Thomas N.] Boston Coll, Dept Biol, Chestnut Hill, MA 02167 USA. [Broekman, Marike L. D.; Leroy, Stanley G.; Tierney, Laryssa A.; Sena-Esteves, Miguel] Massachusetts Gen Hosp, Dept Neurol, Program Neurosci, Charlestown, MA USA. [Broekman, Marike L. D.; Leroy, Stanley G.; Tierney, Laryssa A.; Sena-Esteves, Miguel] Harvard Univ, Sch Med, Charlestown, MA USA. [Broekman, Marike L. D.] Univ Med Ctr Utrecht, Rudolf Magnus Inst Neurosci, Dept Pharmacol & Anat, Utrecht, Netherlands. [Sandberg, Michael A.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Berman Gund Lab Study Retinal Degenerat, Boston, MA USA. [d'Azzo, Alessandra] St Jude Childrens Hosp, Dept Genet, Memphis, TN 38105 USA. RP Baek, RC (reprint author), Boston Coll, Dept Biol, Chestnut Hill, MA 02167 USA. EM Miguel.Esteves@umassmed.edu OI Seyfried, Thomas/0000-0003-1491-3989 FU National Institutes of Health/National Institute of Neurological Disorders and Stroke [R21NS053993] FX National Institutes of Health/National Institute of Neurological Disorders and Stroke grant R21NS053993 (MSE). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 57 TC 24 Z9 24 U1 0 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD OCT 18 PY 2010 VL 5 IS 10 AR e13468 DI 10.1371/journal.pone.0013468 PG 16 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 665ON UT WOS:000283045300036 PM 20976108 ER PT J AU Mega, JL Close, SL Wiviott, SD Shen, L Walker, JR Simon, T Antman, EM Braunwald, E Sabatine, MS AF Mega, Jessica L. Close, Sandra L. Wiviott, Stephen D. Shen, Lei Walker, Joseph R. Simon, Tabassome Antman, Elliott M. Braunwald, Eugene Sabatine, Marc S. TI Genetic variants in ABCB1 and CYP2C19 and cardiovascular outcomes after treatment with clopidogrel and prasugrel in the TRITON-TIMI 38 trial: a pharmacogenetic analysis SO LANCET LA English DT Article ID PERCUTANEOUS CORONARY INTERVENTION; OF-FUNCTION POLYMORPHISM; HEALTHY JAPANESE SUBJECTS; STENT THROMBOSIS; DUODENAL ENTEROCYTES; PLATELET INHIBITION; P-GLYCOPROTEIN; MDR1 GENE; EXPRESSION; RESPONSIVENESS AB Background Clopidogrel and prasugrel are subject to efflux via P-glycoprotein (encoded by ABCB1, also known as MDR1). ABCB1 polymorphisms, particularly 3435C -> T, may affect drug transport and efficacy. We aimed to assess the effect of this polymorphism by itself and alongside variants in CYP2C/9 on cardiovascular outcomes in patients treated with clopidogrel or prasugrel in TRITON-TIMI 38. We also assessed the effect of genotype on the pharmacodynamic and pharmacoldnetic properties of these drugs in healthy individuals. Methods We genotyped ABCB1 in 2932 patients with acute coronary syndromes undergoing percutaneous intervention who were treated with clopidogrel (n=1471) or prasugrel (n=1461) in the TRITON -> TIMI 38 trial. We evaluated the association between ABCB1 3435C -> T and rates of the primary efficacy endpoint (cardiovascular death, myocardial infarction, or stroke) until 15 months. We then assessed the combined effect of ABCB13435C -> T genotype and reduced-function alleles of CYP2C19. 321 healthy individuals were also genotyped, and we tested the association of genetic variants with reduction in maximum platelet aggregation and plasma concentrations of active drug metabolites. Findings In patients treated with clopidogrel, ABCB1 3435C -> T genotype was significantly associated with the risk of cardiovascular death, myocardial infarction, or stroke (p=0.0064). TT homozygotes had a 72% increased risk of the primary endpoint compared with CT/CC individuals (Kaplan-Meier event rates 12.9% [52 of 414] vs 7.8% [80 of 1057 participants]; HR 1.72, 95% CI 1.22-2.44, p=0.002). ABCB1 3435C -> T and CYP2C19 genotypes were significant, independent predictors of the primary endpoint, and 681 (47%) of the 1454 genotyped patients taking clopidogrel who were either CYP2C19 reduced-function allele carriers, ABCB1 3435 TT homozygotes, or both were at increased risk of the primary endpoint (HR 1.97, 95% CI 1.38-2.82, p=0.0002). In healthy participants, 3435 TT homozygotes had an absolute reduction in maximum platelet aggregation with clopidogrel that was 7.3 percentage points less than for CT/CC individuals (p=0.0127). ABCB1 genotypes were not significantly associated with clinical or pharmacological outcomes in patients with an acute coronary syndrome or healthy individuals treated with prasugrel, respectively. Interpretation Individuals with the ABCB1 3435 TT genotype have reduced platelet inhibition and are at increased risk of recurrent ischaemic events during clopidogrel treatment. In patients with acute coronary syndromes who have undergone percutaneous intervention, when both ABCB1 and CYP2C19 are taken into account, nearly half of the population carries a genotype associated with increased risk of major adverse cardiovascular events while on standard doses of clopidogrel. C1 [Mega, Jessica L.; Wiviott, Stephen D.; Antman, Elliott M.; Braunwald, Eugene] Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc, Boston, MA 02115 USA. [Mega, Jessica L.; Wiviott, Stephen D.; Antman, Elliott M.; Braunwald, Eugene; Sabatine, Marc S.] Harvard Univ, Sch Med, Boston, MA USA. [Close, Sandra L.] Indiana Univ, Indianapolis, IN 46204 USA. [Close, Sandra L.; Shen, Lei] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Walker, Joseph R.] Daiichi Sankyo Inc, Edison, NJ USA. [Simon, Tabassome] Univ Paris 06, AP HP, F-75252 Paris 05, France. RP Mega, JL (reprint author), Brigham & Womens Hosp, TIMI Study Grp, Div Cardiovasc, 350 Longwood Ave, Boston, MA 02115 USA. EM jmega@partners.org; msabatine@partners.org FU Daiichi Sankyo; Eli Lilly; Sanofi-Aventis; Bristol-Myers Squibb; AstraZeneca; Schering-Plough/Merck; Johnson Johnson; Bayer Healthcare; National Institutes of Health [K99/R00 HL098461-01]; ARENA; Medco; Portola; Schering-Plough; Servier; Pfizer; Caisse d'Assurance Maladie; Merck FX The TIMI Study Group receives research grant support from Daiichi Sankyo, Eli Lilly, Sanofi-Aventis, Bristol-Myers Squibb, AstraZeneca, Schering-Plough/Merck, Johnson & Johnson, and Bayer Healthcare. Additionally, JLM is supported in part by grant K99/R00 HL098461-01 from the National Institutes of Health and reports consulting fees from Sanofi-Aventis, Bristol-Myers Squibb, and AstraZeneca. SDW reports consulting fees from Sanofi-Aventis, Bristol-Myers Squibb, AstraZeneca, ARENA, Medco, and Portola, and lecture fees for CME from Schering-Plough, Daiichi Sanity, Eli Lilly, Novartis, and AstraZeneca. TS reports research grant support from Servier, Pfizer, Daiichi Sankyo, Eli Lilly, Sanofi-Aventis, AstraZeneca, and Caisse d'Assurance Maladie and consulting fees from Eli Lilly, Daiichi Sankyo, Sanofi-Aventis, Bristol-Myers Squibb, and AstraZeneca. EMA has no additional relationships to disclose. EB reports consulting fees from Daiichi Sankyo and lecture fees from Schering-Plough and Merck. MSS reports consulting fees from AstraZeneca, Bristol-Myers Squibb, Sanofi-Aventis, Daiichi Sanity, and Eli Lilly and lecture fees from Bristol-Myers Squibb, Sanofi-Aventis, and Eli Lilly. JRW is an employee of Daiichi Sanity and holds equity ownership or stock options therein. SLC is a former employee of Eli Lilly and holds equity ownership or stock options therein. LS is an employee of Eli Lilly and holds equity ownership or stock options therein. NR 29 TC 309 Z9 334 U1 3 U2 30 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD OCT 16 PY 2010 VL 376 IS 9749 BP 1312 EP 1319 DI 10.1016/S0140-6736(10)61273-1 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 671RX UT WOS:000283528600033 PM 20801494 ER PT J AU Chan, ED Keane, J Iseman, MD AF Chan, Edward D. Keane, Joseph Iseman, Michael D. TI Should Cigarette Smoke Exposure Be a Criterion to Treat Latent Tuberculous Infection? SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Editorial Material ID TOBACCO SMOKING; PULMONARY TUBERCULOSIS; COLLIDING EPIDEMICS; PASSIVE SMOKING; RISK-FACTOR; ASSOCIATION; METAANALYSIS; MORTALITY; COPD C1 [Chan, Edward D.] Univ Colorado, Denver Vet Affairs Med Ctr, Natl Jewish Hlth, Denver, CO 80202 USA. [Keane, Joseph] Trinity Coll Dublin, Dublin, Ireland. [Keane, Joseph] St James Hosp, Dublin 8, Ireland. RP Chan, ED (reprint author), Univ Colorado, Denver Vet Affairs Med Ctr, Natl Jewish Hlth, Anschutz Med Campus, Denver, CO 80202 USA. OI Keane, Joseph/0000-0001-5313-385X NR 23 TC 5 Z9 5 U1 0 U2 6 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD OCT 15 PY 2010 VL 182 IS 8 BP 990 EP 992 DI 10.1164/rccm.201006-0861ED PG 3 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 669XR UT WOS:000283384000002 PM 20947905 ER PT J AU Vichaiwong, K Purohit, S An, D Toyoda, T Jessen, N Hirshman, MF Goodyear, LJ AF Vichaiwong, Kanokwan Purohit, Suneet An, Ding Toyoda, Taro Jessen, Niels Hirshman, Michael F. Goodyear, Laurie J. TI Contraction regulates site-specific phosphorylation of TBC1D1 in skeletal muscle SO BIOCHEMICAL JOURNAL LA English DT Article DE Akt; AMP-activated protein kinase (AMPK); contraction; glucose transport; skeletal muscle; TEC1D1 ID ACTIVATED PROTEIN-KINASE; STIMULATED GLUCOSE-TRANSPORT; GLUT4 TRANSLOCATION; INSULIN STIMULATION; DIABETES-MELLITUS; AKT SUBSTRATE; LIVING MICE; IN-VIVO; 160 KDA; EXERCISE AB TBC1D1 (tre-2/USP6, BUB2, cdc16 domain family member 1) is a Rab-GAP (GTPase-actvating protein) that is highly expressed in skeletal muscle, but little is known about TBC1D1 regulation and function. We studied TBC1D1 phosphorylation on three predicted AMPK (AMP-activated protein kinase) phosphorylation sites Ser(231), Ser(660) and Ser(700)) and one predicted Akt phosphorylation site (Thr(590)) in control mice, AMPK alpha 2 inactive transgenic mice (AMPK alpha 2i TG) and Akt2-knockout mice (Akt2 KO) Muscle contraction significantly increased TBC1D1 phosphorylation on Ser(231) and Ser(660). tended to increase Ser(700) phosphorylation. but had no effect on Thr(590) AICAR (5-ammoimidazole-4-carboxyamide ribonucleoside) also increased phosphorylation on Ser231. Ser(660) and Ser(700) but not Thr(590). whereas insulin only increased Thr(590) phosphorylation. Basal and contraction-stimulated TBC1D1 Ser(231), Ser(660) and Ser(700) phosphorylation were greatly reduced in AMPK alpha 2i TG mice. although contraction still elicited a small increase in phosphorylation Akt2 KO mice had blunted insulin-stimulated TBC1D1 Thr(590) phosphorylation Contraction-stimulated TBC1D1 Ser(231) and Ser(660) phosphorylation were normal in high-fat-fed mice. Glucose uptake in vivo was significantly decreased in tibialis anterior muscles overexpressing TBC1D1 mutated on four predicted AMPK phosphorylation sites In conclusion, contraction causes site-specific phosphorylation of TBC1D1 in skeletal muscle, and TBC1D1 phosphorylation on AMPK sites regulates contraction-stimulated glucose uptake. AMPK and Akt regulate TBC1D1 phosphorylation, but there must be additional upstream kinases that mediate TBC1D1 phosphorylation in skeletal muscle C1 [Vichaiwong, Kanokwan; Purohit, Suneet; An, Ding; Toyoda, Taro; Jessen, Niels; Hirshman, Michael F.; Goodyear, Laurie J.] Joslin Diabet Ctr, Div Res, Boston, MA 02215 USA. [Goodyear, Laurie J.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Goodyear, Laurie J.] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Goodyear, LJ (reprint author), Joslin Diabet Ctr, Div Res, 1 Joslin Pl, Boston, MA 02215 USA. RI Jessen, Niels/E-1731-2011; OI Jessen, Niels/0000-0001-5613-7274 FU National Institutes of Health [R01 AR42238, R01 AR45670, T32DK007260]; Joslin Diabetes Center; American Diabetes Association; Diabetes Education and Research Center (DERC) [P30 DK36836]; Thailand Research Fund [PHD/0242/2548]; Canadian Institute for Health Research [MFE-83802]; Canadian Diabetes Association [PF-3-07-2255-DA]; Uehara Memorial Foundation; Japan Society for the Promotion of Science; Danish Agency for Science Technology and Innovation [271-07-0719] FX This work was supported by funding from the National Institutes of Health [grant numbers R01 AR42238, R01 AR45670 (to L J G)], a Graetz Challenge Grant from the Joslin Diabetes Center (to L J G), an American Diabetes Association Mentor-based Award (to L J G.), and the Diabetes Education and Research Center (DERC) [grant number P30 DK36836 (Joslin Diabetes Center)] K V was support by the Thailand Research Fund through the Royal Golden Jubilee Ph D Program [grant number PHD/0242/2548] S P was supported by the National Institutes of Health [Training Grant number T32DK007260] D A was supported by fellowships from the Canadian Institute for Health Research [grant number MFE-83802): and a Canadian Diabetes Association Incentive Award [grant number PF-3-07-2255-DA] T T was supported by the Uehara Memorial Foundation, Japan Society for the Promotion of Science and an American Diabetes Association Mentor-based Award (to L J G) N J was supported by the Danish Agency for Science Technology and Innovation [grant number 271-07-0719] NR 45 TC 35 Z9 35 U1 0 U2 4 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD OCT 15 PY 2010 VL 431 BP 311 EP 320 DI 10.1042/BJ20101100 PN 2 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 669VQ UT WOS:000283378700015 PM 20701589 ER PT J AU Camarata, T Snyder, D Schwend, T Klosowiak, J Holtrup, B Simon, HG AF Camarata, Troy Snyder, Diana Schwend, Tyler Klosowiak, Julian Holtrup, Brandon Simon, Hans-Georg TI Pdlim7 is required for maintenance of the mesenchymal/epidermal Fgf signaling feedback loop during zebrafish pectoral fin development SO BMC DEVELOPMENTAL BIOLOGY LA English DT Article ID PDZ-LIM PROTEIN; TRANSCRIPTION FACTOR; T-BOX; SUBCELLULAR-LOCALIZATION; DIFFERENTIAL REGULATION; NUCLEAR-LOCALIZATION; POLARIZING ACTIVITY; HEART DEVELOPMENT; MULTIPLE ROLES; FACTORS ERM AB Background: Vertebrate limb development involves a reciprocal feedback loop between limb mesenchyme and the overlying apical ectodermal ridge (AER). Several gene pathways participate in this feedback loop, including Fgf signaling. In the forelimb lateral plate mesenchyme, Tbx5 activates Fgf10 expression, which in turn initiates and maintains the mesenchyme/AER Fgf signaling loop. Recent findings have revealed that Tbx5 transcriptional activity is regulated by dynamic nucleocytoplasmic shuttling and interaction with Pdlim7, a PDZ-LIM protein family member, along actin filaments. This Tbx5 regulation is critical in heart formation, but the coexpression of both proteins in other developing tissues suggests a broader functional role. Results: Knock-down of Pdlim7 function leads to decreased pectoral fin cell proliferation resulting in a severely stunted fin phenotype. While early gene induction and patterning in the presumptive fin field appear normal, the pectoral fin precursor cells display compaction and migration defects between 18 and 24 hours post-fertilization (hpf). During fin growth fgf24 is sequentially expressed in the mesenchyme and then in the apical ectodermal ridge (AER). However, in pdlim7 antisense morpholino-treated embryos this switch of expression is prevented and fgf24 remains ectopically active in the mesenchymal cells. Along with the lack of fgf24 in the AER, other critical factors including fgf8 are reduced, suggesting signaling problems to the underlying mesenchyme. As a consequence of perturbed AER function in the absence of Pdlim7, pathway components in the fin mesenchyme are misregulated or absent, indicating a breakdown of the Fgf signaling feedback loop, which is ultimately responsible for the loss of fin outgrowth. Conclusion: This work provides the first evidence for the involvement of Pdlim7 in pectoral fin development. Proper fin outgrowth requires fgf24 downregulation in the fin mesenchyme with subsequent activation in the AER, and Pdlim7 appears to regulate this transition, potentially through Tbx5 regulation. By controlling Tbx5 subcellular localization and transcriptional activity and possibly additional yet unknown means, Pdlim7 is required for proper development of the heart and the fins. These new regulatory mechanisms may have important implications how we interpret Tbx5 function in congenital hand/heart syndromes in humans. C1 [Camarata, Troy; Snyder, Diana; Schwend, Tyler; Klosowiak, Julian; Holtrup, Brandon; Simon, Hans-Georg] Northwestern Univ, Feinberg Sch Med, Childrens Mem Res Ctr, Dept Pediat, Chicago, IL 60614 USA. [Camarata, Troy] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Nephrol, Charlestown, MA 02129 USA. [Schwend, Tyler] Kansas State Univ, Div Biol, Manhattan, KS 66502 USA. RP Simon, HG (reprint author), Northwestern Univ, Feinberg Sch Med, Childrens Mem Res Ctr, Dept Pediat, Chicago, IL 60614 USA. EM hgsimon@northwestern.edu FU NIH [R01HL085834] FX We are grateful to Drs. D. Yelon, C. Neumann, and K. Poss for sharing in situ hybridization probes. We would like to thank J. Krcmery for expert technical advice and critical reading of the manuscript. This work is supported by NIH grant R01HL085834 (to H.-G. Simon). NR 70 TC 6 Z9 6 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-213X J9 BMC DEV BIOL JI BMC Dev. Biol. PD OCT 15 PY 2010 VL 10 AR 104 DI 10.1186/1471-213X-10-104 PG 17 WC Developmental Biology SC Developmental Biology GA 673KD UT WOS:000283657400001 PM 20950450 ER PT J AU Sher, DJ Haddad, RI Norris, CM Posner, MR Wirth, LJ Goguen, LA Annino, D Balboni, T Allen, A Tishler, RB AF Sher, David J. Haddad, Robert I. Norris, Charles M., Jr. Posner, Marshall R. Wirth, Lori J. Goguen, Laura A. Annino, Donald Balboni, Tracy Allen, Aaron Tishler, Roy B. TI Efficacy and Toxicity of Reirradiation Using Intensity-Modulated Radiotherapy for Recurrent or Second Primary Head and Neck Cancer SO CANCER LA English DT Article DE head and neck cancer; intensity-modulated radiotherapy; reirradiation; combined modality therapy ID SQUAMOUS-CELL CARCINOMA; LOCALLY ADVANCED HEAD; CONCURRENT CHEMOTHERAPY; INTERGROUP; CHEMORADIOTHERAPY; IRRADIATION; TRIAL AB BACKGROUND: Patients with locally recurrent squamous cell cancer of the head and neck (SCCHN) are reported to have a poor prognosis and limited therapeutic options. Optimal management is selectively applied and morbid. Both surgical resection and chemoradiotherapy are reported to result in median survivals of approximately 12 months. Intensity-modulated radiotherapy (IMRT) is a highly conformal approach for delivering RT. This study reported the experience of the Dana-Farber Cancer Institute (DFCI) with IMRT-based chemoradiotherapy with or without surgery for locally recurrent SCCHN. METHODS: The current study was a retrospective study of all patients treated at DFCI who were diagnosed with nonmetastatic second primary or recurrent SCCHN and who received reirradiation based on IMRT. The primary endpoint was overall survival (OS), and secondary endpoints were locoregional (LRC) and distant control and acute and chronic toxicity. RESULTS: Thirty-five patients were treated from August 2004 until December 2008. Recurrent disease was treated in the oral cavity (4 patients), larynx/hypopharynx (13 patients), oropharynx (7 patients), nasopharynx (2 patients), and neck (9 patients). The median radiation dose was 60 Gray (Gy), and all patients received concurrent chemotherapy. The median follow-up was 2.3 years. The 2-year actuarial OS and LRC rates were 48% and 67%, respectively. Approximately 91% and 46%, respectively, of all patients developed at least 1 acute and late grade 3 toxicity. Four (11%) late deaths occurred in patients with no evidence of disease (2 aspiration events, 1 oropharyngeal hemorrhage, and 1 infectious death). CONCLUSIONS: Aggressive chemoradiotherapy with IMRT was found to be feasible and resulted in favorable survival outcomes in comparison with published reports. Acute and late toxicities were substantial. The apparently improved LRC appears to carry a significant risk of developing late complications. Cancer 2010; 116: 4761-8. (C) 2010 American Cancer Society. C1 [Sher, David J.; Balboni, Tracy; Tishler, Roy B.] Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Haddad, Robert I.; Posner, Marshall R.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Haddad, Robert I.; Posner, Marshall R.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Norris, Charles M., Jr.; Goguen, Laura A.; Annino, Donald] Brigham & Womens Hosp, Dept Surg, Div Otolaryngol, Boston, MA 02115 USA. [Wirth, Lori J.] Massachusetts Gen Hosp, Dept Med Oncol, Boston, MA 02114 USA. [Allen, Aaron] Rabin Med Ctr, Dept Radiat Oncol, Tel Aviv, Israel. RP Sher, DJ (reprint author), Brigham & Womens Hosp, Dana Farber Canc Inst, Dept Radiat Oncol, 44 Binney St, Boston, MA 02115 USA. EM dsher@lroc.harvard.edu NR 18 TC 36 Z9 36 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD OCT 15 PY 2010 VL 116 IS 20 BP 4761 EP 4768 DI 10.1002/cncr.25305 PG 8 WC Oncology SC Oncology GA 663SS UT WOS:000282910800017 PM 20572036 ER PT J AU McCullough, L Ng, A Najita, J Janov, A Henderson, T Mauch, P Diller, L AF McCullough, Laura Ng, Andrea Najita, Julie Janov, Abbe Henderson, Tara Mauch, Peter Diller, Lisa TI Breastfeeding in Survivors of Hodgkin Lymphoma Treated With Chest Radiotherapy SO CANCER LA English DT Article DE Hodgkin lymphoma; chest radiation; radiotherapy; breastfeeding; late effects; survivors ID LONG-TERM SURVIVORS; FOLLOW-UP TIME; RADIATION-THERAPY; CANCER-RISK; CONSERVING THERAPY; 2ND MALIGNANCIES; DISEASE; LACTATION; PREGNANCY; CHILDHOOD AB BACKGROUND: Female survivors of therapeutic chest radiation often question whether they will have difficulty with breast feeding, given their prior exposure to breast radiation. In the current study, the rates of successful breastfeeding in long-term survivors who received chest radiotherapy (CXRT) as a treatment for Hodgkin lymphoma (HL) were examined. METHODS: A survey study of survivors of HL who were treated at the Joint Center for Radiation Therapy in Boston from 1969 through 1996 was performed. Patients were queried about childbearing and breastfeeding. The authors analyzed self-reported breastfeeding success in women who reported live births after CXRT and compared them with a sibling control group. RESULTS: Overall, 83 female survivors of HL who were treated with CXRT reported at least 1 birth after treatment. There were a total of 141 post-HL pregnancies resulting in births. In these women, the median age at the time of the HL diagnosis was 23 years (range, 14-40 years) and the median radiation dose was 41 grays (Gy) (range, 27-46 Gy). For survivors, 57 of the 94 (61%) breastfeeding attempts were successful, whereas within the control group, 74 of the 94 (79%) attempts were successful (P = .044). Accounting for maternal age at first birth and birth era, multivariable analysis suggested that HL survivors treated with CXRT may be less likely to breastfeed successfully than their siblings (odds ratio, 0.42; 95% confidence interval, 0.2-1.0 [P = .06]). CONCLUSIONS: The majority of female HL survivors who were treated with CXRT report being able to breastfeed successfully. However, the results of the current study indicate a trend toward less successful breastfeeding in survivors as a previously unreported late effect of radiation. Cancer 2010; 116: 4866-71. (C) 2010 American Cancer Society. C1 [McCullough, Laura; Diller, Lisa] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [McCullough, Laura; Diller, Lisa] Childrens Hosp Boston, Dept Med, Boston, MA USA. [McCullough, Laura; Ng, Andrea; Mauch, Peter; Diller, Lisa] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Ng, Andrea; Mauch, Peter] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Najita, Julie; Janov, Abbe] Dana Farber Canc Inst, Dept Biostat, Boston, MA USA. [Najita, Julie; Janov, Abbe] Dana Farber Canc Inst, Dept Computat Biol, Boston, MA 02115 USA. [Henderson, Tara] Univ Chicago, Dept Pediat Oncol, Chicago, IL 60637 USA. RP McCullough, L (reprint author), Dana Farber Canc Inst, Dept Pediat Oncol, 44 Binney St, Boston, MA 02115 USA. EM laura.mccullough@childrens.harvard.edu NR 38 TC 5 Z9 5 U1 0 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD OCT 15 PY 2010 VL 116 IS 20 BP 4866 EP 4871 DI 10.1002/cncr.25442 PG 6 WC Oncology SC Oncology GA 663SS UT WOS:000282910800029 PM 20629028 ER PT J AU Lee, KK Todorova, K Mandinova, A AF Lee, Kevin K. Todorova, Kristina Mandinova, Anna TI Maximizing early detection of esophageal squamous cell carcinoma via SILAC-proteomics SO CANCER BIOLOGY & THERAPY LA English DT Editorial Material DE esophageal squamous cell carcinoma; tumor secretome; SILAC; biomarker; cancer detection; LC-MS/MS; MALDI-TOF ID QUANTITATIVE PROTEOMICS; CANCER; PROTEIN; IDENTIFICATION; MARKER; CARCINOGENESIS; AUTOANTIBODY; EXPRESSION; BLOOD C1 [Lee, Kevin K.; Todorova, Kristina; Mandinova, Anna] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA. [Lee, Kevin K.; Todorova, Kristina; Mandinova, Anna] Harvard Univ, Sch Med, Charlestown, MA USA. [Lee, Kevin K.; Mandinova, Anna] MIT, Cambridge Ctr, Cambridge, MA 02139 USA. RP Mandinova, A (reprint author), Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA USA. EM amandinova@partners.org FU NCI NIH HHS [CA140615, R01 CA140615] NR 22 TC 1 Z9 2 U1 0 U2 2 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD OCT 15 PY 2010 VL 10 IS 8 BP 811 EP 813 DI 10.4161/cbt.10.8.13754 PG 3 WC Oncology SC Oncology GA 665PB UT WOS:000283046800010 PM 20953140 ER PT J AU Cole, AM Myant, K Reed, KR Ridgway, RA Athineos, D Van den Brink, GR Muncan, V Clevers, H Clarke, AR Sicinski, P Sansom, OJ AF Cole, Alicia M. Myant, Kevin Reed, Karen R. Ridgway, Rachel A. Athineos, Dimitris Van den Brink, Gijs R. Muncan, Vanesa Clevers, Hans Clarke, Alan R. Sicinski, Peter Sansom, Owen J. TI Cyclin D2-Cyclin-Dependent Kinase 4/6 Is Required for Efficient Proliferation and Tumorigenesis following Apc Loss SO CANCER RESEARCH LA English DT Article ID BETA-CATENIN; MOUSE INTESTINE; CELL-PROLIFERATION; COLORECTAL-CANCER; IN-VIVO; MYC; D1; EXPRESSION; INHIBITION; TARGET AB Inactivation of the Apc gene is recognized as the key early event in the development of sporadic colorectal cancer (CRC), where its loss leads to constitutive activation of beta-catenin/T-cell factor 4 signaling and hence transcription of Wnt target genes such as c-Myc. Our and other previous studies have shown that although cyclin D1 is required for adenoma formation, it is not immediately upregulated following Apc loss within the intestine, suggesting that proliferation following acute Apc loss may be dependent on another D-type cyclin. In this study, we investigated the expression and functional relevance of cyclin D2 following Apc loss in the intestinal epithelium. Cyclin D2 is upregulated immediately following Apc loss, which corresponded with a significant increase in cyclin-dependent kinase 4 (CDK4) and hyperphosphorylated Rb levels. Deficiency of cyclin D2 resulted in a reduction in enterocyte proliferation and crypt size within Apc-deficient intestinal epithelium. Moreover, cyclin D2 dramatically reduced tumor growth and development in Apc(Min/+) mice. Importantly, cyclin D2 knockout did not affect proliferation of normal enterocytes, and furthermore, CDK4/6 inhibition also suppressed the proliferation of adenomatous cells and not normal cells from Apc(Min/+) mice. Taken together, these results indicate that cyclin D-CDK4/6 complexes are required for the efficient proliferation of cells with deregulated Wnt signaling, and inhibiting this complex may be an effective chemopreventative strategy in CRC. Cancer Res; 70(20); 8149-58. (C) 2010 AACR. C1 [Cole, Alicia M.; Myant, Kevin; Ridgway, Rachel A.; Athineos, Dimitris; Sansom, Owen J.] Beatson Inst Canc Res, Glasgow G61 1BD, Lanark, Scotland. [Reed, Karen R.] Sch Biosci, Cardiff, S Glam, Wales. [Van den Brink, Gijs R.; Muncan, Vanesa] Leiden Univ, Med Ctr, Leiden, Netherlands. [Muncan, Vanesa; Clevers, Hans] Netherlands Inst Dev Biol, Hubrecht Lab, NL-3584 CT Utrecht, Netherlands. [Clarke, Alan R.; Sicinski, Peter] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Clarke, Alan R.; Sicinski, Peter] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Sansom, OJ (reprint author), Beatson Inst Canc Res, Switchback Rd,Garscube Estate, Glasgow G61 1BD, Lanark, Scotland. EM o.sansom@beatson.gla.ac.uk RI Clarke, Alan/A-6256-2008; Reed, Karen/B-8813-2011; clarke, alan/P-2820-2014; OI Reed, Karen/0000-0002-7467-1718; Clarke, Alan/0000-0002-4281-426X; Athineos, Dimitris/0000-0001-5298-7941; Sansom, Owen J./0000-0001-9540-3010 FU Cancer Research UK [R01 CA083688, CA108420] FX Cancer Research UK and R01 CA083688 and CA108420 (P. Sicinski). P. Sicinski is a Scholar of the Leukemia and Lymphoma Society. NR 30 TC 32 Z9 33 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 15 PY 2010 VL 70 IS 20 BP 8149 EP 8158 DI 10.1158/0008-5472.CAN-10-0315 PG 10 WC Oncology SC Oncology GA 663JG UT WOS:000282879900041 PM 20736363 ER PT J AU Kim, J Woo, AJ Chu, JL Snow, JW Fujiwara, Y Kim, CG Cantor, AB Orkin, SH AF Kim, Jonghwan Woo, Andrew J. Chu, Jianlin Snow, Jonathan W. Fujiwara, Yuko Kim, Chul Geun Cantor, Alan B. Orkin, Stuart H. TI A Myc Network Accounts for Similarities between Embryonic Stem and Cancer Cell Transcription Programs SO CELL LA English DT Article ID HISTONE ACETYLTRANSFERASE COMPLEX; HUMAN SOMATIC-CELLS; C-MYC; SELF-RENEWAL; RNAI SCREEN; DEVELOPMENTAL REGULATORS; ESSENTIAL COFACTOR; DEFINED FACTORS; PLURIPOTENCY; CHROMATIN AB c-Myc (Myc) is an important transcriptional regulator in embryonic stem (ES) cells, somatic cell reprogramming, and cancer. Here, we identify a Myc-centered regulatory network in ES cells by combining protein-protein and protein-DNA interaction studies and show that Myc interacts with the NuA4 complex, a regulator of ES cell identity. In combination with regulatory network information, we define three ES cell modules (Core, Polycomb, and Myc) and show that the modules are functionally separable, illustrating that the overall ES cell transcription program is composed of distinct units. With these modules as an analytical tool, we have reassessed the hypothesis linking an ES cell signature with cancer or cancer stem cells. We find that the Myc module, independent of the Core module, is active in various cancers and predicts cancer outcome. The apparent similarity of cancer and ES cell signatures reflects, in large part, the pervasive nature of Myc regulatory networks. C1 [Kim, Jonghwan; Woo, Andrew J.; Chu, Jianlin; Snow, Jonathan W.; Fujiwara, Yuko; Cantor, Alan B.; Orkin, Stuart H.] Childrens Hosp, Dept Pediat Oncol, Boston, MA 02115 USA. [Kim, Jonghwan; Woo, Andrew J.; Chu, Jianlin; Snow, Jonathan W.; Fujiwara, Yuko; Cantor, Alan B.; Orkin, Stuart H.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Kim, Jonghwan; Chu, Jianlin; Snow, Jonathan W.; Fujiwara, Yuko; Orkin, Stuart H.] Harvard Stem Cell Inst, Boston, MA 02115 USA. [Kim, Jonghwan; Woo, Andrew J.; Chu, Jianlin; Snow, Jonathan W.; Fujiwara, Yuko; Cantor, Alan B.; Orkin, Stuart H.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Fujiwara, Yuko; Orkin, Stuart H.] Howard Hughes Med Inst, Boston, MA 02115 USA. [Kim, Chul Geun] Hanyang Univ, Dept Life Sci, Seoul 133791, South Korea. RP Orkin, SH (reprint author), Childrens Hosp, Dept Pediat Oncol, 300 Longwood Ave, Boston, MA 02115 USA. EM stuart_orkin@dfci.harvard.edu FU NIH/NIGMS [K99GM088384] FX We thank Jennifer Trowbridge for critical reading of the manuscript, the Taplin Biological Mass Spectrometry Facility at Harvard Medical School for mass-spectrometry and peptide identification, and the Microarray Core Facility at the Dana Farber Cancer Institute for ChIP sample processing. The project described is partially supported by Award Number K99GM088384 to J.K. from the NIH/NIGMS. S.H.O. is an investigator of the Howard Hughes Medical Institute. NR 52 TC 320 Z9 323 U1 0 U2 19 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD OCT 15 PY 2010 VL 143 IS 2 BP 313 EP 324 DI 10.1016/j.cell.2010.09.010 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 665RC UT WOS:000283052200019 PM 20946988 ER PT J AU Jones, MD Liu, JC Barthel, TK Hussain, S Lovria, E Cheng, DF Schoonmaker, JA Mulay, S Ayers, DC Bouxsein, ML Stein, GS Mukherjee, S Lian, JB AF Jones, Marci D. Liu, Julie C. Barthel, Thomas K. Hussain, Sadiq Lovria, Erik Cheng, Dengfeng Schoonmaker, Jesse A. Mulay, Sudhanshu Ayers, David C. Bouxsein, Mary L. Stein, Gary S. Mukherjee, Siddhartha Lian, Jane B. TI A Proteasome Inhibitor, Bortezomib, Inhibits Breast Cancer Growth and Reduces Osteolysis by Downregulating Metastatic Genes SO CLINICAL CANCER RESEARCH LA English DT Article ID MYELOMA BONE-DISEASE; MULTIPLE-MYELOMA; IN-VIVO; OSTEOBLAST DIFFERENTIATION; OSTEOCLAST FUNCTION; CELLS; ACTIVATION; THERAPY; PATHWAY; MICE AB Purpose: The incidence of bone metastasis in advanced breast cancer (BrCa) exceeds 70%. Bortezomib, a proteasome inhibitor used for the treatment of multiple myeloma, also promotes bone formation. We tested the hypothesis that proteasome inhibitors can ameliorate BrCa osteolytic disease. Experimental Design: To address the potentially beneficial effect of bortezomib in reducing tumor growth in the skeleton and counteracting bone osteolysis, human MDA-MB-231 BrCa cells were injected into the tibia of mice to model bone tumor growth for in vivo assessment of treatment regimens before and after tumor growth. Results: Controls exhibited tumor growth, destroying trabecular and cortical bone and invading muscle. Bortezomib treatment initiated following inoculation of tumor cells strikingly reduced tumor growth, restricted tumor cells mainly to the marrow cavity, and almost completely inhibited osteolysis in the bone micro-environment over a 3-to 4-week period as shown by [(18)F] fluorodeoxyglucose positron emission tomography, micro-computed tomography scanning, radiography, and histology. Thus, proteasome inhibition is effective in killing tumor cells within the bone. Pretreatment with bortezomib for 3 weeks before inoculation of tumor cells was also effective in reducing osteolysis. Our in vitro and in vivo studies indicate that mechanisms by which bortezomib inhibits tumor growth and reduces osteolysis result from inhibited cell proliferation, necrosis, and decreased expression of factors that promote BrCa tumor progression in bone. Conclusion: These findings provide a basis for a novel strategy to treat patients with BrCa osteolytic lesions, and represent an approach for protecting the entire skeleton from metastatic bone disease. Clin Cancer Res; 16(20); 4978-89. (C) 2010 AACR. C1 [Jones, Marci D.; Liu, Julie C.; Hussain, Sadiq; Stein, Gary S.; Lian, Jane B.] Univ Massachusetts, Dept Cell Biol, Sch Med, Worcester, MA 01655 USA. [Jones, Marci D.; Liu, Julie C.; Hussain, Sadiq; Stein, Gary S.; Lian, Jane B.] Univ Massachusetts, Ctr Canc, Sch Med, Worcester, MA 01655 USA. [Jones, Marci D.; Barthel, Thomas K.; Lovria, Erik; Ayers, David C.] Univ Massachusetts, Dept Orthoped & Phys Rehabil, Sch Med, Worcester, MA 01655 USA. [Cheng, Dengfeng] Univ Massachusetts, Div Nucl Med, Sch Med, Dept Radiol, Worcester, MA 01655 USA. [Bouxsein, Mary L.] Beth Israel Deaconess Med Ctr, Ctr Adv Orthoped Studies, Boston, MA 02215 USA. [Schoonmaker, Jesse A.; Mulay, Sudhanshu; Mukherjee, Siddhartha] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Mukherjee, Siddhartha] Columbia Univ, Herbert Irving Comprehens Canc Ctr, New York, NY USA. RP Lian, JB (reprint author), Univ Massachusetts, Dept Cell Biol, Sch Med, 55 Lake Ave N, Worcester, MA 01655 USA. EM jane.lian@umassmed.edu RI Liu, Julie/H-7496-2013 OI Liu, Julie/0000-0003-0784-2529 FU Zimmer, Inc.; Musculoskeletal Transplant Foundation (MTF); NIH [P01CA082834, S10RR023540, F32AR055030]; Diabetes Endocrinology Research Center [DK32520] FX D.C. Ayers: commercial research grant, Zimmer, Inc.; other commercial research support, Musculoskeletal Transplant Foundation (MTF).; Studies reported were in part supported by NIH grants P01CA082834, S10RR023540, and F32AR055030. Core resources supported by the Diabetes Endocrinology Research Center grant DK32520 were also used. J.B. Lian is a member of the University of Massachusetts Diabetes and Endocrinology Resource Center (DK32520). The contents of this manuscript are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. NR 47 TC 27 Z9 31 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD OCT 15 PY 2010 VL 16 IS 20 BP 4978 EP 4989 DI 10.1158/1078-0432.CCR-09-3293 PG 12 WC Oncology SC Oncology GA 663IT UT WOS:000282877700010 PM 20843837 ER PT J AU Chakkalakal, JV Nishimune, H Ruas, JL Spiegelman, BM Sanes, JR AF Chakkalakal, Joe V. Nishimune, Hiroshi Ruas, Jorge L. Spiegelman, Bruce M. Sanes, Joshua R. TI Retrograde influence of muscle fibers on their innervation revealed by a novel marker for slow motoneurons SO DEVELOPMENT LA English DT Article DE Fast muscle fiber; Motoneuron; Neuromuscular junction; SV2A; Slow muscle fiber; PGC1 alpha (PPARGC1 alpha); Mouse ID SYNAPTIC VESICLE PROTEIN; PRENATAL RAT HINDLIMB; HEAVY-CHAIN ISOFORMS; MOTOR UNITS; ADHESION MOLECULES; SKELETAL-MUSCLE; GENE-REGULATION; FAST-TWITCH; GASTROCNEMIUS; CAT AB Mammalian limb and trunk skeletal muscles are composed of muscle fibers that differ in contractile and molecular properties. They are commonly divided into four categories according to the myosin heavy chain that they express: I, IIA, IIX and IIB, ranging from slowest to fastest. Individual motor axons innervate tens of muscle fibers, nearly all of which are of the same type. The mechanisms accounting for this striking specificity, termed motor unit homogeneity, remain incompletely understood, in part because there have been no markers for motoneuron types. Here we show in mice that the synaptic vesicle protein SV2A is selectively localized in motor nerve terminals on slow ( type I and small type IIA) muscle fibers; its close relatives, SV2B and SV2C, are present in all motor nerve terminals. SV2A is broadly expressed at birth; fast motoneurons downregulate its expression during the first postnatal week. An inducible transgene incorporating regulatory elements from the Sv2a gene permits selective labeling of slow motor units and reveals their composition. Overexpression of the transcriptional co-regulator PGC1 alpha in muscle fibers, which converts them to a slow phenotype, leads to an increased frequency of SV2A-positive motor nerve terminals, indicating a fiber type-specific retrograde influence of muscle fibers on their innervation. This retrograde influence must be integrated with known anterograde influences in order to understand how motor units become homogeneous. C1 [Chakkalakal, Joe V.; Nishimune, Hiroshi; Sanes, Joshua R.] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. [Chakkalakal, Joe V.; Nishimune, Hiroshi; Sanes, Joshua R.] Harvard Univ, Ctr Brain Sci, Cambridge, MA 02138 USA. [Nishimune, Hiroshi] Univ Kansas Med Sch, Dept Anat & Cell Biol, Kansas City, KS 66160 USA. [Ruas, Jorge L.; Spiegelman, Bruce M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Sanes, JR (reprint author), Harvard Univ, Dept Mol & Cellular Biol, 52 Oxford St, Cambridge, MA 02138 USA. EM sanesj@mcb.harvard.edu RI Nishimune, Hiroshi/B-7226-2013; OI Chakkalakal, Joe/0000-0002-8440-7312; Ruas, Jorge/0000-0002-1110-2606 FU NIH [NS19195, NS59853, DK54477]; CIHR FX We thank K. T. Brannan, Renate Lewis, Debbie Pelusi and Monica Chu for assistance, Jean Livet and Ryan Draft for advice, T. C. Sudhof for antibodies, and N. A. Jenkins and N. G. Copeland for recombineering vectors. This work was supported by grants from the NIH to J.R.S. (NS19195 and NS59853) and B. M. S. (DK54477). J.V.C. was supported by a Tim E. Noel Fellowship in ALS from the CIHR. Deposited in PMC for release after 12 months. NR 53 TC 28 Z9 28 U1 0 U2 7 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD OCT 15 PY 2010 VL 137 IS 20 BP 3489 EP 3499 DI 10.1242/dev.053348 PG 11 WC Developmental Biology SC Developmental Biology GA 655AN UT WOS:000282213100016 PM 20843861 ER PT J AU Stadtfeld, M Hochedlinger, K AF Stadtfeld, Matthias Hochedlinger, Konrad TI Induced pluripotency: history, mechanisms, and applications SO GENES & DEVELOPMENT LA English DT Review DE ES cells; iPS cells; pluripotency; reprogramming ID EMBRYONIC STEM-CELLS; HUMAN SOMATIC-CELLS; PRIMORDIAL GERM-CELLS; HUMAN IPS CELLS; GENE-EXPRESSION SIGNATURES; OLFACTORY SENSORY NEURONS; HUMAN CORD BLOOD; NUCLEAR TRANSFER; DEFINED FACTORS; SELF-RENEWAL AB The generation of induced pluripotent stem cells (iPSCs) from somatic cells demonstrated that adult mammalian cells can be reprogrammed to a pluripotent state by the enforced expression of a few embryonic transcription factors. This discovery has raised fundamental questions about the mechanisms by which transcription factors influence the epigenetic conformation and differentiation potential of cells during reprogramming and normal development. In addition, iPSC technology has provided researchers with a unique tool to derive disease-specific stem cells for the study and possible treatment of degenerative disorders with autologous cells. In this review, we summarize the progress that has been made in the iPSC field over the last 4 years, with an emphasis on understanding the mechanisms of cellular reprogramming and its potential applications in cell therapy. C1 [Stadtfeld, Matthias; Hochedlinger, Konrad] Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA. [Stadtfeld, Matthias; Hochedlinger, Konrad] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Stadtfeld, Matthias; Hochedlinger, Konrad] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA. [Stadtfeld, Matthias; Hochedlinger, Konrad] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Stadtfeld, Matthias; Hochedlinger, Konrad] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. [Stadtfeld, Matthias; Hochedlinger, Konrad] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. RP Hochedlinger, K (reprint author), Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA. EM khochedlinger@helix.mgh.harvard.edu RI liang, yan/H-3894-2011; OI Stadtfeld, Matthias/0000-0002-5852-9906 FU Howard Hughes Medical Institute; NICHD NIH HHS [R01 HD058013] NR 255 TC 386 Z9 402 U1 29 U2 245 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 OCT 15 PY 2010 VL 24 IS 20 BP 2239 EP 2263 DI 10.1101/gad.1963910 PG 25 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 665QJ UT WOS:000283050200003 PM 20952534 ER PT J AU Khaled, M Levy, C Fisher, DE AF Khaled, Mehdi Levy, Carmit Fisher, David E. TI Control of melanocyte differentiation by a MITF-PDE4D3 homeostatic circuit SO GENES & DEVELOPMENT LA English DT Article DE cAMP; MITF; PDE4D; skin; pigmentation ID CAMP-SPECIFIC PHOSPHODIESTERASES; MICROPHTHALMIA GENE-PRODUCT; PROTEIN-KINASE; SPLICE VARIANTS; SKIN-CANCER; ACTIVATION; EXPRESSION; MITF; PHOSPHORYLATION; PIGMENTATION AB Cyclic AMP (cAMP) is a ubiquitous second messenger that regulates a variety of biological processes. The magnitude and duration of cAMP expression are regulated by both production and hydrolysis. Melanocyte-stimulating hormone (MSH) plays a crucial role in pigment cell differentiation via cAMP-regulated expression of the master transcription factor MITF. We report the identification of phosphodiesterase 4D3 as a direct target of the MSH/cAMP/MITF pathway. This creates a negative feedback loop that induces refractoriness to chronic stimulation of the cAMP pathway in melanocytes. This homeostatic pathway highlights a potent mechanism controlling melanocyte differentiation that may be amenable to pharmacologic manipulation for skin cancer prevention. C1 [Khaled, Mehdi; Levy, Carmit; Fisher, David E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr,Dept Dermatol, Boston, MA 02114 USA. RP Fisher, DE (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cutaneous Biol Res Ctr,Dept Dermatol, Boston, MA 02114 USA. EM dfisher3@partners.org RI khaled, mehdi/C-4854-2012 FU Philippe Foundation; National Institutes of Health (NIAMS) [AR043369-15, 1AR058469]; Melanoma Research Alliance; US/Israel Binational Science Foundation; Adelson Medical Research Foundation; Doris Duke Charitable Foundation FX We thank Andre Rosowsky, Kathleen C. Robinson, and Su-Jean Seo for critical comments on the manuscript, and Scott Granter, Hans Widlund, Akinori Kawakami, Rosa Veguilla, and Satoru Yokoyama for discussions and help with technical aspects of the study. We also thank Riham Carden and Abraham Cooper, who participated in early portions of the project. We thank Takahiro Kunisada for providing the C57BL6 K14SCF mouse. M.K. acknowledges the Philippe Foundation for their support. D.E.F. gratefully acknowledges support for this research from the National Institutes of Health (NIAMS AR043369-15 and 1AR058469), the Melanoma Research Alliance, the US/Israel Binational Science Foundation, The Adelson Medical Research Foundation, and the Doris Duke Charitable Foundation. NR 31 TC 22 Z9 25 U1 0 U2 2 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 OCT 15 PY 2010 VL 24 IS 20 BP 2276 EP 2281 DI 10.1101/gad.1937710 PG 6 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 665QJ UT WOS:000283050200006 PM 20952536 ER PT J AU Blauw, HM Al-Chalabi, A Andersen, PM van Vught, PWJ Diekstra, FP van Es, MA Saris, CGJ Groen, EJN van Rheenen, W Koppers, M van't Slot, R Strengman, E Estrada, K Rivadeneira, F Hofman, A Uitterlinden, AG Kiemeney, LA Vermeulen, SHM Birve, A Waibel, S Meyer, T Cronin, S McLaughlin, RL Hardiman, O Sapp, PC Tobin, MD Wain, LV Tomik, B Slowik, A Lemmens, R Rujescu, D Schulte, C Gasser, T Brown, RH Landers, JE Robberecht, W Ludolph, AC Ophoff, RA Veldink, JH van den Berg, LH AF Blauw, Hylke M. Al-Chalabi, Ammar Andersen, Peter M. van Vught, Paul W. J. Diekstra, Frank P. van Es, Michael A. Saris, Christiaan G. J. Groen, Ewout J. N. van Rheenen, Wouter Koppers, Max van't Slot, Ruben Strengman, Eric Estrada, Karol Rivadeneira, Fernando Hofman, Albert Uitterlinden, Andre G. Kiemeney, Lambertus A. Vermeulen, Sita H. M. Birve, Anna Waibel, Stefan Meyer, Thomas Cronin, Simon McLaughlin, Russell L. Hardiman, Orla Sapp, Peter C. Tobin, Martin D. Wain, Louise V. Tomik, Barbara Slowik, Agnieszka Lemmens, Robin Rujescu, Dan Schulte, Claudia Gasser, Thomas Brown, Robert H., Jr. Landers, John E. Robberecht, Wim Ludolph, Albert C. Ophoff, Roel A. Veldink, Jan H. van den Berg, Leonard H. TI A large genome scan for rare CNVs in amyotrophic lateral sclerosis SO HUMAN MOLECULAR GENETICS LA English DT Article ID COPY-NUMBER VARIATION; WIDE ASSOCIATION; RECURRENT MICRODELETIONS; STRUCTURAL VARIATION; SPORADIC ALS; NIPA1 GENE; SUSCEPTIBILITY; MUTATIONS; DPP6; POPULATION AB Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease selectively affecting motor neurons in the brain and spinal cord. Recent genome-wide association studies (GWASs) have identified several common variants which increase disease susceptibility. In contrast, rare copy-number variants (CNVs), which have been associated with several neuropsychiatric traits, have not been studied for ALS in well-powered study populations. To examine the role of rare CNVs in ALS susceptibility, we conducted a CNV association study including over 19 000 individuals. In a genome-wide screen of 1875 cases and 8731 controls, we did not find evidence for a difference in global CNV burden between cases and controls. In our association analyses, we identified two loci that met our criteria for follow-up: the DPP6 locus (OR = 3.59, P = 6.6 x 10(-3)), which has already been implicated in ALS pathogenesis, and the 15q11.2 locus, containing NIPA1 (OR = 12.46, P = 9.3 x 10(-5)), the gene causing hereditary spastic paraparesis type 6 (HSP 6). We tested these loci in a replication cohort of 2559 cases and 5887 controls. Again, results were suggestive of association, but did not meet our criteria for independent replication: DPP6 locus: OR = 1.92, P = 0.097, pooled results: OR = 2.64, P = 1.4 x 10(-3); NIPA1: OR = 3.23, P = 0.041, pooled results: OR = 6.20, P = 2.2 x 10(-5)). Our results highlight DPP6 and NIPA1 as candidates for more in-depth studies. Unlike other complex neurological and psychiatric traits, rare CNVs with high effect size do not play a major role in ALS pathogenesis. C1 [Blauw, Hylke M.; van Vught, Paul W. J.; Diekstra, Frank P.; van Es, Michael A.; Saris, Christiaan G. J.; Groen, Ewout J. N.; van Rheenen, Wouter; Koppers, Max; Veldink, Jan H.; van den Berg, Leonard H.] Univ Med Ctr Utrecht, Dept Neurol, Rudolf Magnus Inst Neurosci, NL-3584 CX Utrecht, Netherlands. [van't Slot, Ruben; Strengman, Eric] Univ Med Ctr Utrecht, Complex Genet Sect, Div Biomed Genet, Dept Med Genet, NL-3584 CX Utrecht, Netherlands. [Ophoff, Roel A.] Rudolf Magnus Inst Pharmacol, NL-3584 CX Utrecht, Netherlands. [Al-Chalabi, Ammar] Kings Coll London, Inst Psychiat, Dept Clin Neurosci, MRC,Ctr Neurodegenerat Res, London SE5 8AF, England. [Andersen, Peter M.; Birve, Anna] Umea Univ, Inst Pharmacol & Clin Neurosci, SE-90185 Umea, Sweden. [Andersen, Peter M.; Waibel, Stefan; Ludolph, Albert C.] Univ Ulm, Dept Neurol, D-89081 Ulm, Germany. [Estrada, Karol; Rivadeneira, Fernando; Uitterlinden, Andre G.] Erasmus Univ, Med Ctr Rotterdam, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands. [Rivadeneira, Fernando; Hofman, Albert; Uitterlinden, Andre G.] Erasmus Univ, Med Ctr Rotterdam, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands. [Kiemeney, Lambertus A.; Vermeulen, Sita H. M.] Radboud Univ Nijmegen, Med Ctr, Dept Epidemiol Biostat & HTA, NL-6500 HB Nijmegen, Netherlands. [Meyer, Thomas] Humboldt Univ, Charite Univ Hosp, Dept Neurol, D-13353 Berlin, Germany. [Cronin, Simon; McLaughlin, Russell L.; Hardiman, Orla] Beaumont Hosp, Dept Neurol, Dublin 9, Ireland. [Hardiman, Orla] Univ Dublin Trinity Coll, Trinity Coll Inst Neurosci, Dublin 2, Ireland. [Sapp, Peter C.; Brown, Robert H., Jr.; Landers, John E.] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA 02129 USA. [Sapp, Peter C.; Brown, Robert H., Jr.; Landers, John E.] Univ Massachusetts, Sch Med, Dept Neurol, Worcester, MA 01655 USA. [Sapp, Peter C.] Howard Hughes Med Inst, Cambridge, MA 01605 USA. [Sapp, Peter C.] MIT, Dept Biol, Cambridge, MA 01605 USA. [Tobin, Martin D.; Wain, Louise V.] Univ Leicester, Dept Hlth Sci, Leicester LE1 7RH, Leics, England. [Tobin, Martin D.; Wain, Louise V.] Univ Leicester, Dept Genet, Leicester LE1 7RH, Leics, England. [Tomik, Barbara; Slowik, Agnieszka] Jagiellonian Univ, Dept Neurol, PL-31007 Krakow, Poland. [Lemmens, Robin; Robberecht, Wim] Katholieke Univ Leuven, Univ Hosp Leuven, Dept Neurol, B-3000 Leuven, Belgium. [Lemmens, Robin; Robberecht, Wim] Katholieke Univ Leuven VIB, Vesalius Res Ctr, B-3000 Leuven, Belgium. [Rujescu, Dan] Univ Munich, Dept Psychiat, Div Mol & Clin Neurobiol, D-80336 Munich, Germany. [Schulte, Claudia; Gasser, Thomas] Univ Tubingen, Hertie Inst Clin Brain Res, Dept Neurodegenerat Dis, D-72074 Tubingen, Germany. [Schulte, Claudia; Gasser, Thomas] German Ctr Neurodegenerat Dis, D-72074 Tubingen, Germany. [Ophoff, Roel A.] Univ Calif Los Angeles, Ctr Neurobehav Genet, Los Angeles, CA USA. RP van den Berg, LH (reprint author), Univ Med Ctr Utrecht, Dept Neurol, Rudolf Magnus Inst Neurosci, Heidelberglaan 100, NL-3584 CX Utrecht, Netherlands. EM l.h.vandenberg@umcutrecht.nl RI Al-Chalabi, Ammar/E-5361-2010; Kiemeney, Lambertus/D-3357-2009; Saris, C.G.J./L-4623-2015; Rivadeneira, Fernando/O-5385-2015; Vermeulen, H.H.M./L-4716-2015; Groen, Ewout/L-5081-2016; OI Al-Chalabi, Ammar/0000-0002-4924-7712; Kiemeney, Lambertus/0000-0002-2368-1326; Rivadeneira, Fernando/0000-0001-9435-9441; Hardiman, Orla/0000-0003-2610-1291; McLaughlin, Russell/0000-0003-3915-2135; Groen, Ewout/0000-0002-2330-9444; Koppers, Max/0000-0002-7751-1082; Schulte, Claudia/0000-0003-4006-1265; Wain, Louise/0000-0003-4951-1867 FU Prinses Beatrix Fonds; VSB fonds; H. Kersten and M. Kersten (Kersten Foundation); Netherlands ALS Foundation; J.R. van Dijk and the Adessium Foundation; Brain Foundation of The Netherlands; Netherlands Organization of Scientific Research NWO Investments [175.010.2005.011, 911-03-012]; Research Institute for Diseases in the Elderly (RIDE2) [014-93-015]; Netherlands Genomics Initiative (NGI)/Netherlands Organisation for Scientific Research (NWO) [050-060-810]; Erasmus Medical Center; Erasmus University, Rotterdam; Netherlands Organization for the Health Research and Development (ZonMw); Research Institute for Diseases in the Elderly (RIDE); Ministry of Education, Culture and Science; Ministry for Health, Welfare and Sports; European Commission (DG XII); Municipality of Rotterdam; RUNMC; Muscular Dystrophy Association (USA); Health Research Board of Ireland; Irish Neurological Association; Irish Motor Neuron Disease Research Foundation FX This project was supported by the Prinses Beatrix Fonds, VSB fonds, H. Kersten and M. Kersten (Kersten Foundation), The Netherlands ALS Foundation and J.R. van Dijk and the Adessium Foundation (L.H.v.d.B.). J.H.V. is supported by the Brain Foundation of The Netherlands. The GWA study was funded by the Netherlands Organization of Scientific Research NWO Investments (nr. 175.010.2005.011, 911-03-012), the Research Institute for Diseases in the Elderly (014-93-015; RIDE2), the Netherlands Genomics Initiative (NGI)/Netherlands Organisation for Scientific Research (NWO) project nr. 050-060-810. The Rotterdam Study is funded by Erasmus Medical Center and Erasmus University, Rotterdam, Netherlands Organization for the Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (DG XII) and the Municipality of Rotterdam. The Dutch controls from the Radboud University Nijmegen Medical Center (RUNMC) are part of the Nijmegen Biomedical Study, a survey from the general population of the municipality of Nijmegen which was conducted with an investment grant of the RUNMC. The Irish studies were funded by The Muscular Dystrophy Association (USA), The Health Research Board of Ireland, The Irish Neurological Association Travel Award and The Irish Motor Neuron Disease Research Foundation. NR 50 TC 24 Z9 24 U1 1 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 EI 1460-2083 J9 HUM MOL GENET JI Hum. Mol. Genet. PD OCT 15 PY 2010 VL 19 IS 20 BP 4091 EP 4099 DI 10.1093/hmg/ddq323 PG 9 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 657UF UT WOS:000282439700017 PM 20685689 ER PT J AU Fernandes, MS Reddy, MM Croteau, NJ Walz, C Weisbach, H Podar, K Band, H Carroll, M Reiter, A Larson, RA Salgia, R Griffin, JD Sattler, M AF Fernandes, Margret S. Reddy, Mamatha M. Croteau, Nicole J. Walz, Christoph Weisbach, Henry Podar, Klaus Band, Hamid Carroll, Martin Reiter, Andreas Larson, Richard A. Salgia, Ravi Griffin, James D. Sattler, Martin TI Novel Oncogenic Mutations of CBL in Human Acute Myeloid Leukemia That Activate Growth and Survival Pathways Depend on Increased Metabolism SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACQUIRED UNIPARENTAL DISOMY; BCR/ABL-TRANSFORMED-CELLS; C-CBL; TYROSINE KINASES; DOWN-REGULATION; NEGATIVE REGULATION; V-CBL; FLT3; EXPRESSION; ABL AB Acute myeloid leukemia (AML) is characterized by multiple mutagenic events that affect proliferation, survival, as well as differentiation. Recently, gain-of-function mutations in the alpha helical structure within the linker sequence of the E3 ubiquitin ligase CBL have been associated with AML. We identified four novel CBL mutations, including a point mutation (Y371H) and a putative splice site mutation in AML specimens. Characterization of these two CBL mutants revealed that coexpression with the receptor tyrosine kinases FLT3 (Fms-like tyrosine kinase 3) or KIT-induced ligand independent growth or ligand hyperresponsiveness, respectively. Growth of cells expressing mutant CBL required expression and kinase activity of FLT3. In addition to the CBL-dependent phosphorylation of FLT3 and CBL itself, transformation was associated with activation of Akt and STAT5 and required functional expression of the small GTPases Rho, Rac, and Cdc42. Furthermore, the mutations led to constitutively elevated intracellular reactive oxygen species levels, which is commonly linked to increased glucose metabolism in cancer cells. Inhibition of hexokinase with 2-deoxyglucose blocked the transforming activity of CBL mutants and reduced activation of signaling mechanisms. Overall, our data demonstrate that mutations of CBL alter cellular biology at multiple levels and require not only the activation of receptor proximal signaling events but also an increase in cellular glucose metabolism. Pathways that are activated by CBL gain-of-function mutations can be efficiently targeted by small molecule drugs. C1 [Fernandes, Margret S.; Reddy, Mamatha M.; Croteau, Nicole J.; Weisbach, Henry; Podar, Klaus; Griffin, James D.; Sattler, Martin] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Fernandes, Margret S.; Reddy, Mamatha M.; Podar, Klaus; Griffin, James D.; Sattler, Martin] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. [Walz, Christoph] Univ Heidelberg, Univ Med Mannheim, Inst Pathol, D-69120 Heidelberg, Germany. [Walz, Christoph; Reiter, Andreas] Univ Heidelberg, Univ Med Mannheim, Med Klin 3, D-69120 Heidelberg, Germany. [Podar, Klaus] Univ Heidelberg, Natl Ctr Tumor Dis NCT, D-69120 Heidelberg, Germany. [Band, Hamid] Univ Nebraska Med Ctr, Eppley Inst, Omaha, NE 68198 USA. [Band, Hamid] Univ Nebraska Med Ctr, Dept Genet, Coll Med, Omaha, NE 68198 USA. [Band, Hamid] Univ Nebraska Med Ctr, Dept Cell Biol & Anat, Coll Med, Omaha, NE 68198 USA. [Band, Hamid] Univ Nebraska Med Ctr, Dept Biochem & Mol Biol, Coll Med, Omaha, NE 68198 USA. [Carroll, Martin] Univ Penn, Div Hematol & Oncol, Philadelphia, PA 19104 USA. [Larson, Richard A.; Salgia, Ravi] Univ Chicago, Dept Med, Chicago, IL 60637 USA. RP Sattler, M (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St, Boston, MA 02115 USA. EM martin_sattler@dfci.harvard.edu OI Larson, Richard/0000-0001-9168-3203 FU National Institutes of Health [5R01CA134660-02, 5R01CA116552-04, 5R01CA99163-09, 5R01CA87986-12, 5R01CA105489-06, 5R01CA10075006, 5R01CA125541-04, 5R01CA129501]; Leukemia and Lymphoma Society SCOR; German Jose Carreras Leukemia Foundation [DJCLS R06/02]; United States Department of Defense; Adams Barr Program in Innovative Cancer Research FX This work was supported, in whole or in part, by National Institutes of Health Grants 5R01CA134660-02 (to M.S.), 5R01CA116552-04, 5R01CA99163-09, 5R01CA87986-12, and 5R01CA105489-06 (to H.B.), and 5R01CA10075006, 5R01CA125541-04, and 5R01CA129501-02 (to R.S.), a Leukemia and Lymphoma Society SCOR grant (to J.D.G.), German Jose Carreras Leukemia Foundation Grant DJCLS R06/02 (to C.W.), the United States Department of Defense, and the Adams Barr Program in Innovative Cancer Research (to M.S.). NR 42 TC 22 Z9 23 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 15 PY 2010 VL 285 IS 42 BP 32596 EP 32605 DI 10.1074/jbc.M110.106161 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 660XZ UT WOS:000282683000074 PM 20622007 ER PT J AU Huang, JM Levitsky, LL Rhoads, DB AF Huang, Jianmin Levitsky, Lynne L. Rhoads, David B. TI Boosting native promoter activities with non-adjacent response-element multimers SO JOURNAL OF BIOTECHNOLOGY LA English DT Article DE Promoter; Gene expression; Multiple response elements; Augmentation strategy; Gene therapy ID LOCUS-CONTROL REGIONS; I ALPHA-GENE; TRANSCRIPTION FACTOR; BETA-CELLS; EXPRESSION; YOUNG; INSULIN; LIVER; ACTIVATION; MUTATIONS AB Effective gene therapy requites regulated gene expression and vector safety We developed a strategy to exponentially increase native promoter activity while retaining inherent regulation by inserting multi-copy response elements (REs) into non-adjacent locations For the hepatocyte nuclear factor (HNF) 4 alpha-dependent Hnf1a (MODY3) gene HNF4 alpha stimulation increased from 5- to 90-fold by inserting 3 additional HNF4 alpha REs (H4REs) Constructing a promoter with two 4xH4REs 0 25 kb apart by duplicating the 4xH4RE fragment increased stimulation to >1000-fold HNF4 alpha-induced protein expression by the duplicate 4xH4RE Hnf1a promoter was comparable to a viral promoter Converting the two Apolipoprotein C3 (ApoC3) H4REs spaced 061 kb apart to 4xH4REs achieved a similar result Increasing spacing to 2 1 kb with non promoter DNA abolished the augmentation Finally converting the HNF1 alpha RE of the HNF4A (MODY1) P2 promoter to 4xH1RE and adding a second 4xH1RE0 84 kb upstream increased HNF1 alpha stimulation from 26- to >200-fold Deleting intervening DNA to produce 023-kb spacing increased stimulation to >500-fold Spaced multi-copy RE motifs is a novel strategy for engineering promoters that boosts activity far beyond other techniques Augmentation of three promoters suggests that this approach is potentially applicable to other promoters for gene therapy and might obviate the need for viral promoters (C) 2010 Elsevier B V All rights reserved C1 [Rhoads, David B.] MassGen Hosp Children, Pediat Endocrine Unit, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Rhoads, DB (reprint author), MassGen Hosp Children, Pediat Endocrine Unit, 55 Fruit St BHX410, Boston, MA 02114 USA. FU American Diabetes Association [7-05-RA-121]; Diabetes Action Research & Education Foundation [204]; Harvard University; Nicholas Dulong Diabetes Research Fund FX This work was supported by American Diabetes Association Research Grant 7-05-RA-121 (DBR) Diabetes Action Research & Education Foundation Grant #204 (DBR) Harvard University Milton Fund (DBR) and the Nicholas Dulong Diabetes Research Fund (LLL) NR 45 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1656 J9 J BIOTECHNOL JI J. Biotechnol. PD OCT 15 PY 2010 VL 150 IS 2 BP 259 EP 267 DI 10.1016/j.jbiotec.2010.09.929 PG 9 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 682GB UT WOS:000284388300008 PM 20850486 ER PT J AU Alter, G Moody, MA AF Alter, Galit Moody, M. Anthony TI The Humoral Response to HIV-1: New Insights, Renewed Focus SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; T-CELL DEPLETION; NEUTRALIZING ANTIBODY-RESPONSES; ACTIVE ANTIRETROVIRAL THERAPY; HUMAN MONOCLONAL-ANTIBODIES; PROXIMAL EXTERNAL REGION; GASTROINTESTINAL-TRACT; LYMPH-NODES; FC-RECEPTOR; INFECTION AB During the past 2 decades, significant advances in our understanding of the humoral immune response to human immunodeficiency virus type 1 (HIV-1) infection have been made, yet a tremendous amount of work lies ahead. Despite these advances, strategies to reliably induce antibodies that can control HIV-1 infection are still critically needed. However, recent advances in our understanding of the kinetics, specificity, and function of early humoral responses offer alternative new approaches to attain this goal. These results, along with the new broadly neutralizing antibody specificities, the role for other antibody functions, the increased understanding of HIV-1-induced changes to B cell biology, and results from the RV144 "Thai" trial showing potential modest sterilizing protection by nonneutralizing antibody responses, have renewed focus on the humoral system. In this review, recent advances in our understanding of the earliest humoral responses are discussed, highlighting presentations from the meeting on the Biology of Acute HIV Infection. C1 [Alter, Galit; Moody, M. Anthony] Duke Univ, Med Ctr, Duke Human Vaccine Inst, Dept Pediat, Durham, NC 27710 USA. [Alter, Galit] Massachusetts Gen Hosp, Infect Dis Unit, Ragon Inst MGH Massachusetts Inst Technol & Harva, Boston, MA 02114 USA. [Alter, Galit] Harvard Univ, Sch Med, Div Aids, Boston, MA USA. RP Moody, MA (reprint author), Duke Univ, Med Ctr, Duke Human Vaccine Inst, Dept Pediat, Box 103020 DUMC, Durham, NC 27710 USA. EM moody007@mc.duke.edu OI Moody, Tony/0000-0002-3890-5855 FU Bill and Melinda Gates Foundation; Center For HIV/AIDS Vaccine Immunology [U19 AI067854]; National Institutes of Health [R01 AI080289]; Office of AIDS Research, National Institutes of Health FX Bill and Melinda Gates Foundation (Collaboration for AIDS Vaccine Discovery grant), Center For HIV/AIDS Vaccine Immunology (grant U19 AI067854), and National Institutes of Health (grant R01 AI080289).; This article is part of a supplement entitled "Primary HIV-1 Infection," sponsored by the Office of AIDS Research, National Institutes of Health. NR 57 TC 26 Z9 27 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD OCT 15 PY 2010 VL 202 SU 2 BP S315 EP S322 DI 10.1086/655654 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 651FJ UT WOS:000281911000008 PM 20846039 ER PT J AU Bell, SK Little, SJ Rosenberg, ES AF Bell, Sigall K. Little, Susan J. Rosenberg, Eric S. TI Clinical Management of Acute HIV Infection: Best Practice Remains Unknown SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; COMBINATION ANTIRETROVIRAL THERAPY; TRANSMITTED DRUG-RESISTANCE; T-CELL RESPONSES; TYPE-1 INFECTION; VIRAL LOAD; IMMUNE-RESPONSES; CONTROLLED TRIAL; NATURAL-HISTORY; SET-POINT AB Best practice for the clinical management of acute human immunodeficiency virus (HIV) infection remains unknown. Although some data suggest possible immunologic, virologic, or clinical benefit of early treatment, other studies show no difference in these outcomes over time, after early treatment is discontinued. The literature on acute HIV infection is predominantly small nonrandomized studies, which further limits interpretation. As a result, the physician is left to grapple with these uncertainties while making clinical decisions for patients with acute HIV infection. Here we review the literature, focusing on the potential advantages and disadvantages of treating acute HIV infection outlined in treatment guidelines, and summarize the presentations on clinical management of acute HIV infection from the 2009 Acute HIV Infection Meeting in Boston, Massachusetts. C1 [Rosenberg, Eric S.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Boston, MA 02114 USA. [Bell, Sigall K.] Beth Israel Deaconess Med Ctr, Div Infect Dis, Boston, MA 02215 USA. [Little, Susan J.] Univ Calif San Diego, Div Infect Dis, San Diego, CA 92103 USA. RP Rosenberg, ES (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Infect Dis, Gray J-504,55 Fruit St, Boston, MA 02114 USA. EM erosenberg1@partners.org RI Hartman, Megan/G-4054-2012 FU Merck Laboratories; National Institutes of Health [AI074621, R01 AI071915]; Office of AIDS Research, National Institutes of Health FX S.J.L. has received research support from Merck Laboratories, and S.J.L. and E.S.R. have received research support from the National Institutes of Health. S.K.B. reports no conflict.; National Institutes of Health (grants AI074621 to S.J.L. and R01 AI071915 to E.S.R.).; This article is part of a supplement entitled "Primary HIV-1 Infection," sponsored by the Office of AIDS Research, National Institutes of Health. NR 73 TC 33 Z9 33 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD OCT 15 PY 2010 VL 202 SU 2 BP S278 EP S288 DI 10.1086/655655 PG 11 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 651FJ UT WOS:000281911000003 PM 20846034 ER PT J AU Boutwell, CL Rolland, MM Herbeck, JT Mullins, JI Allen, TM AF Boutwell, Christian L. Rolland, Morgane M. Herbeck, Joshua T. Mullins, James I. Allen, Todd M. TI Viral Evolution and Escape during Acute HIV-1 Infection SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; T-LYMPHOCYTE ESCAPE; REPLICATION CAPACITY; ELITE CONTROLLERS; VACCINE DESIGN; CTL ESCAPE; TRANSMISSION; MUTATIONS; VARIANTS; EPITOPES AB The extensive genetic diversity of human immunodeficiency virus type 1 (HIV-1) presents a significant barrier to the development of an effective and durable HIV vaccine. This variability not only makes it difficult to identify the targets against which immune responses should be directed, but it also confers on the virus the capacity for rapid escape from effective immune responses. Here, we describe recent investigations of the genetic diversity of HIV-1 at transmission and of the evolution of the virus as it adapts to the host immune environment during the acute phase of HIV-1 infection. These studies increase our understanding of the virology of the earliest stages of HIV-1 infection and provide critical insights into the mechanisms underlying viral replication and immune control of diverse HIV-1 strains. Such knowledge will inform the design of smarter, more effective vaccines capable of inducing immune control of HIV-1. C1 [Boutwell, Christian L.; Allen, Todd M.] Ragon Inst MGH MIT & Harvard, Boston, MA USA. [Rolland, Morgane M.; Herbeck, Joshua T.; Mullins, James I.] Univ Washington, Sch Med, Dept Microbiol, Seattle, WA 98195 USA. [Rolland, Morgane M.; Herbeck, Joshua T.; Mullins, James I.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA. RP Allen, TM (reprint author), Massachusetts Gen Hosp, 149 13th St, Charlestown, MA 02129 USA. EM tallen2@partners.org RI Allen, Todd/F-5473-2011 FU Bill and Melinda Gates Foundation; National Institute of Allergy and Infectious Diseases [P01-AI074415, P01-AI57005, T32-AI07245, T32-AI0714]; Computation Biology Core of the University of Washington Center for AIDS Research [P30-AI27757]; amfAR Mathilde Krim Fellowship [107005-43-RNT]; Office of AIDS Research, National Institutes of Health FX This project was funded in part by the Bill and Melinda Gates Foundation (to C.L.B., J.I.M., and T.M.A.); the National Institute of Allergy and Infectious Diseases, under grant P01-AI074415 (to C.L.B. and T.M.A.), grant P01-AI57005 (to J.I.M), grant T32-AI07245 (to C.L.B.), and grant T32-AI0714 (to J.T.H.); the Computation Biology Core of the University of Washington Center for AIDS Research (P30-AI27757; to M.M.R., J.T.H., and J.I.M.); and the amfAR Mathilde Krim Fellowship (107005-43-RNT; to M.M.R.).; This article is part of a supplement entitled "Primary HIV-1 Infection," sponsored by the Office of AIDS Research, National Institutes of Health. NR 43 TC 41 Z9 42 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD OCT 15 PY 2010 VL 202 SU 2 BP S309 EP S314 DI 10.1086/655653 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 651FJ UT WOS:000281911000007 PM 20846038 ER PT J AU Chang, JJ Altfeld, M AF Chang, J. Judy Altfeld, Marcus TI Innate Immune Activation in Primary HIV-1 Infection SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID PLASMACYTOID DENDRITIC CELLS; NATURAL-KILLER-CELLS; CD4(+) T-CELLS; INTERFERON-ALPHA; I INTERFERON; TYPE-1 INFECTION; HLA-B; EXPRESSION; AIDS; REPLICATION AB There is growing evidence that highlights the role of the immune response during acute human immunodeficiency virus type 1 (HIV-1) infection in the control or development of disease. The adaptive immune responses do not appear until after HIV-1 infection is already well established, so the role of earlier and faster-responding innate immunity needs to be more closely scrutinized. In particular, 2 aspects of innate immunity for which there are growing research developments will be examined in this review: the actions of type I interferons and natural killer cells. These two components of the innate immune response contribute to viral control both by killing infected cells and by modulating other immune cells that develop. However, the role of interferon a in immune activation is a double-edged sword, causing recruitment of adaptive immune cells that can assist in viral control but concurrently contributing to immune activation-dependent disease progression. Understanding the complexity of how innate responses affect the outcome of HIV-1 infection will help in the development of vaccines that can use innate immunity to enhance viral control with minimal pathogenesis. C1 Harvard Univ, Sch Med, Boston, MA USA. Massachusetts Gen Hosp, Ragon Inst MGH MIT & Harvard, Boston, MA 02114 USA. RP Altfeld, M (reprint author), Massachusetts Gen Hosp, Ragon Inst MGH MIT & Harvard, Bldg 149,13th St,6th Floor, Navy Yard, MA 02129 USA. EM maltfeld@partners.org FU National Institute of Allergy and Infectious Diseases, National Institutes of Health; Office of AIDS Research, National Institutes of Health FX Financial support: National Institute of Allergy and Infectious Diseases, National Institutes of Health.; This article is part of a supplement entitled "Primary HIV-1 Infection," sponsored by the Office of AIDS Research, National Institutes of Health. NR 40 TC 47 Z9 48 U1 0 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD OCT 15 PY 2010 VL 202 SU 2 BP S297 EP S301 DI 10.1086/655657 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 651FJ UT WOS:000281911000005 PM 20846036 ER PT J AU D'Souza, MP Axten, KL Hecht, FM Altfeld, M AF D'Souza, M. Patricia Axten, Karen L. Hecht, Frederick M. Altfeld, Marcus TI Acute HIV-1 Infection: What's New? Where Are We Going? INTRODUCTION SO JOURNAL OF INFECTIOUS DISEASES LA English DT Editorial Material ID IMMUNITY; VACCINE; STEP AB This supplemental issue of the Journal of Infectious Diseases is devoted to the important topic of primary human immunodeficiency virus type 1 (HIV-1) infection. It was prompted by the planning of the Acute HIV-1 Infection Meeting in Boston in September 2009, at which leading scientists and practitioners gathered to discuss new insights into the early, critical events of HIV-1 infection. The reviews that follow underline the current state of the field with regard to transmission biology of HIV-1; the clinical presentation, diagnosis, and management of primary HIV-1 infection; the pathogenesis of primary HIV-1 infection; and innate and adaptive immune responses to the virus. We trust that these findings have the potential to influence the development of effective vaccine strategies. C1 [D'Souza, M. Patricia] NIAID, Vaccine Clin Res Branch, Div Aids, NIH, Bethesda, MD 20892 USA. [Hecht, Frederick M.] Univ Calif San Francisco, San Francisco Gen Hosp, Dept Med, San Francisco, CA 94143 USA. [Axten, Karen L.; Altfeld, Marcus] Ragon Inst MGH MIT & Harvard, Boston, MA USA. RP Altfeld, M (reprint author), Massachusetts Gen Hosp, Ragon Inst MGH MIT & Harvard, Bldg 149,13th St,6th Floor, Charlestown Navy Yard, MA 02129 USA. EM maltfeld@partners.org NR 13 TC 4 Z9 4 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD OCT 15 PY 2010 VL 202 SU 2 BP S267 EP S269 DI 10.1086/655650 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 651FJ UT WOS:000281911000001 PM 20846032 ER PT J AU Streeck, H Nixon, DF AF Streeck, Hendrik Nixon, Douglas F. TI T Cell Immunity in Acute HIV-1 Infection SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID CHRONIC VIRAL-INFECTION; VIRUS TYPE-1 INFECTION; HEPATITIS-C; IN-VITRO; MEMORY; HELP; VIREMIA; MAINTENANCE; LYMPHOCYTES; RESPONSES AB Exceedingly high viral loads and rapid loss of CD4(+) T cells in all tissue compartments are a hallmark of acute human immunodeficiency virus type 1 (HIV-1) infection, which is often accompanied by clinical symptoms such as fever, maculopapular rash, and/or lymphadenopathy. The resolution of the clinical symptoms and the subsequent decrease in plasma viremia are associated with the emergence of HIV-1-specific CD4(+) and CD8(+) T cell responses. The remarkable early inhibition of viremia by CD8(+) T cells appears to be precipitated by only a limited number of specific CD8(+) T cell responses, and the plasma viremia is reduced to a "set point" level. Over time, the breadth and magnitude of CD8(+) T cell responses increase, but without a change in the control of viral replication or further reduction in the viral set point. Moreover, the early viral set point, consequent on the first CD8(+) T cell responses, is highly predictive of the later course of disease progression. Thus, HIV-1-specific CD8(+) T cell responses in acute HIV-1 infection appear uniquely able to efficiently suppress viral replication, whereas CD8(+) T cell responses generated in the chronic phase of infection appear often impaired. C1 [Streeck, Hendrik] Massachusetts Gen Hosp, Ragon Inst MGH MIT & Harvard, Boston, MA 02114 USA. [Streeck, Hendrik] Harvard Univ, Sch Med, Boston, MA USA. [Nixon, Douglas F.] Univ San Francisco, Div Expt Med, San Francisco, CA 94117 USA. RP Streeck, H (reprint author), Massachusetts Gen Hosp, Ragon Inst MGH MIT & Harvard, Boston, MA 02114 USA. OI Nixon, Douglas/0000-0002-2801-1786 FU Bill and Melinda Gates Foundation; National Institutes of Health [P01 AI074415, AI68498]; Office of AIDS Research, National Institutes of Health FX Bill and Melinda Gates Foundation (H.S.); National Institutes of Health (grants P01 AI074415 to H.S. and AI68498 to D.F.N.).; This article is part of a supplement entitled "Primary HIV-1 Infection," sponsored by the Office of AIDS Research, National Institutes of Health. NR 44 TC 38 Z9 39 U1 0 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD OCT 15 PY 2010 VL 202 SU 2 BP S302 EP S308 DI 10.1086/655652 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 651FJ UT WOS:000281911000006 PM 20846037 ER PT J AU Wu, X Chen, KW Yao, L Ayutyanont, N Langbaum, JBS Fleisher, A Reschke, C Lee, W Liu, XF Alexander, GE Bandy, D Foster, NL Thompson, PM Harvey, DJ Weiner, MW Koeppe, RA Jagust, WJ Reiman, EM AF Wu, Xia Chen, Kewei Yao, Li Ayutyanont, Napatkamon Langbaum, Jessica B. S. Fleisher, Adam Reschke, Cole Lee, Wendy Liu, Xiaofen Alexander, Gene E. Bandy, Dan Foster, Norman L. Thompson, Paul M. Harvey, Danielle J. Weiner, Michael W. Koeppe, Robert A. Jagust, William J. Reiman, Eric M. CA Alzheimer's Dis Neuroimaging Initi TI Assessing the reliability to detect cerebral hypometabolism in probable Alzheimer's disease and amnestic mild cognitive impairment SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE Alzheimer's disease; MCI; FDG-PET; Reproducibility of results; Reliability; Bootstrap resampling; Family-wise error; SPM ID POSITRON-EMISSION-TOMOGRAPHY; APOLIPOPROTEIN-E; DEMENTIA; ABNORMALITIES AB Fluorodeoxyglucose positron emission tomography (FDG-PET) studies report characteristic patterns of cerebral hypometabolism in probable Alzheimer's disease (pAD) and amnestic mild cognitive impairment (aMCI). This study aims to characterize the consistency of regional hypometabolism in pAD and aMCI patients enrolled in the AD neuroimaging initiative (ADNI) using statistical parametric mapping (SPM) and bootstrap resampling, and to compare bootstrap-based reliability index to the commonly used type-I error approach with or without correction for multiple comparisons. Batched SPM5 was run for each of 1000 bootstrap iterations to compare FDG-PET images from 74 pAD and 142 aMCI patients, respectively, to 82 normal controls. Maps of the hypometabolic voxels detected for at least a specific percentage of times over the 1000 runs were examined and compared to an overlap of the hypometabolic maps obtained from 3 randomly partitioned independent sub-datasets. The results from the bootstrap derived reliability of regional hypometabolism in the overall data set were similar to that observed in each of the three non-overlapping sub-sets using family-wise error. Strong but non-linear association was found between the bootstrap-based reliability index and the type-I error. For threshold p = 0.0005, pAD was associated with extensive hypometabolic voxels in the posterior cingulate/precuneus and parietotemporal regions with reliability between 90% and 100%. Bootstrap analysis provides an alternative to the parametric family-wise error approach used to examine consistency of hypometabolic brain voxels in pAD and aMCI patients. These results provide a foundation for the use of bootstrap analysis characterize statistical ROIs or search regions in both cross-sectional and longitudinal FDG-PET studies. This approach offers promise in the early detection and tracking of AD, the evaluation of AD-modifying treatments, and other biologically or clinical important measurements using brain images and voxel-based data analysis techniques. (C) 2010 Elsevier B.V. All rights reserved. C1 [Chen, Kewei; Ayutyanont, Napatkamon; Langbaum, Jessica B. S.; Fleisher, Adam; Reschke, Cole; Lee, Wendy; Liu, Xiaofen; Bandy, Dan; Reiman, Eric M.] Banner Alzheimers Inst, Phoenix, AZ USA. [Wu, Xia; Yao, Li] Beijing Normal Univ, Sch Informat Sci & Technol, Beijing 100875, Peoples R China. [Chen, Kewei] Univ Arizona, Dept Radiol, Tucson, AZ 85724 USA. [Chen, Kewei] Arizona State Univ, Sch Math & Stat, Tempe, AZ USA. [Fleisher, Adam] Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA. [Thompson, Paul M.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. [Alexander, Gene E.] Univ Arizona, Dept Psychol, Phoenix, AZ USA. [Alexander, Gene E.] Univ Arizona, Evelyn F McKnight Brain Inst, Phoenix, AZ USA. [Foster, Norman L.] Univ Utah, Ctr Alzheimers Care Imaging & Res, Salt Lake City, UT 84112 USA. [Foster, Norman L.] Univ Utah, Dept Neurol, Salt Lake City, UT 84112 USA. [Weiner, Michael W.] Univ Calif San Francisco, Dept Med Radiol Psychiat & Neurol, San Francisco, CA 94143 USA. [Weiner, Michael W.] San Francisco VA Med Ctr, Ctr Imaging & Neurodegenerat Dis, San Francisco, CA USA. [Koeppe, Robert A.] Univ Michigan, Dept Radiol, Div Nucl Med, Ann Arbor, MI 48109 USA. [Jagust, William J.] Univ Calif Berkeley, Sch Publ Hlth, Helen Wills Neurosci Inst, Berkeley, CA 94720 USA. [Chen, Kewei; Yao, Li] Beijing Normal Univ, State Key Lab Cognit Neurosci & Learning, Beijing 100875, Peoples R China. [Harvey, Danielle J.] Univ Calif Davis, Davis, CA 95616 USA. [Chen, Kewei; Ayutyanont, Napatkamon; Langbaum, Jessica B. S.; Fleisher, Adam; Reschke, Cole; Lee, Wendy; Liu, Xiaofen; Alexander, Gene E.; Bandy, Dan; Reiman, Eric M.] Arizona Alzheimers Consortium, Phoenix, AZ USA. RP Chen, KW (reprint author), Banner Alzheimers Inst, Phoenix, AZ USA. EM kewei.chen@bannerhealth.com RI Scharre, Douglas/E-4030-2011; Chen, kewei/P-6304-2015 OI Chen, kewei/0000-0001-8497-3069 FU National Natural Science Foundation of China [60931003, 60905063, 60805040, 90820019]; National Institute of Mental Health, US [R01 MH57899]; National Institute on Aging, US [9R01AG031581-10, P30 AG19610, k23 AG24062]; State of Arizona; Alzheimer's Disease Neuroimaging Initiative (ADNI; National Institutes of Health) [U01 AG024904]; National Institute on Aging; National Institute of Biomedical Imaging and Bioengineering; NIH [P30 AG010129, K01 AG030514]; Dana Foundation FX This work was supported by the Key Program of National Natural Science Foundation of China (60931003) and National Natural Science Foundation of China (60905063, 60805040, and 90820019). It is also supported by the National Institute of Mental Health, US (R01 MH57899), the National Institute on Aging, US (9R01AG031581-10 and P30 AG19610, k23 AG24062) and the state of Arizona.; Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI; National Institutes of Health Grant U01 AG024904). ADNI is funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Abbott, AstraZeneca AB, Bayer Schering Pharma AG, Bristol-Myers Squibb, Eisai Global Clinical Development, Elan Corporation, Genentech, GE Healthcare, GlaxoSmithKline, Innogenetics, Johnson and Johnson, Eli Lilly and Co., Medpace, Inc., Merck and Co., Inc., Novartis AG, Pfizer Inc, F. Hoffman-La Roche, Schering-Plough, Synarc, Inc., and Wyeth, as well as non-profit partners the Alzheimer's Association and Alzheimer's Drug Discovery Foundation, with participation from the U.S. Food and Drug Administration. Private sector contributions to ADNI are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for NeuroImaging at the University of California, Los Angeles. This research was also supported by NIH grants P30 AG010129, K01 AG030514, and the Dana Foundation. NR 14 TC 8 Z9 8 U1 2 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 J9 J NEUROSCI METH JI J. Neurosci. Methods PD OCT 15 PY 2010 VL 192 IS 2 BP 277 EP 285 DI 10.1016/j.jneumeth.2010.07.030 PG 9 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 663YK UT WOS:000282925900014 PM 20678521 ER PT J AU Garcia, I Mayol, G Rodriguez, E Sunol, M Gershon, TR Rios, J Cheung, NKV Kieran, MW George, RE Perez-Atayde, AR Casala, C Galvan, P de Torres, C Mora, J Lavarino, C AF Garcia, Idoia Mayol, Gemma Rodriguez, Eva Sunol, Mariona Gershon, Timothy R. Rios, Jose Cheung, Nai-Kong V. Kieran, Mark W. George, Rani E. Perez-Atayde, Antonio R. Casala, Carla Galvan, Patricia de Torres, Carmen Mora, Jaume Lavarino, Cinzia TI Expression of the neuron-specific protein CHD5 is an independent marker of outcome in neuroblastoma SO MOLECULAR CANCER LA English DT Article ID TUMOR-SUPPRESSOR GENE; N-MYC AMPLIFICATION; STAGE NEUROBLASTOMA; RISK STRATIFICATION; CLASSIFICATION; DIFFERENTIATION; SIGNATURE; ORIGINS; 1P36.31; SYSTEM AB Background: The chromodomain, helicase DNA-binding protein 5 (CHD5) is a potential tumor suppressor gene located on chromosome 1p36, a region recurrently deleted in high risk neuroblastoma (NB). Previous data have shown that CHD5 mRNA is present in normal neural tissues and in low risk NB, nevertheless, the distribution of CHD5 protein has not been explored. The aim of this study was to investigate CHD5 protein expression as an immunohistochemical marker of outcome in NB. With this purpose, CHD5 protein expression was analyzed in normal neural tissues and neuroblastic tumors (NTs). CHD5 gene and protein expression was reexamined after induction chemotherapy in a subset of high risk tumors to identify potential changes reflecting tumor response. Results: We provide evidence that CHD5 is a neuron-specific protein, absent in glial cells, with diverse expression amongst neuron types. Within NTs, CHD5 immunoreactivity was found restricted to differentiating neuroblasts and ganglion-like cells, and absent in undifferentiated neuroblasts and stromal Schwann cells. Correlation between protein and mRNA levels was found, suggesting transcriptional regulation of CHD5. An immunohistochemical analysis of 90 primary NTs highlighted a strong association of CHD5 expression with favorable prognostic variables (age at diagnosis <12 months, low clinical stage, and favorable histology; P < 0.001 for all), overall survival (OS) (P < 0.001) and event-free survival (EFS) (P < 0.001). Multivariate analysis showed that CHD5 prognostic value is independent of other clinical and biologically relevant parameters, and could therefore represent a marker of outcome in NB that can be tested by conventional immunohistochemistry. The prognostic value of CHD5 was confirmed in an independent, blinded set of 32 NB tumors (P < 0.001). Reactivation of CHD5 expression after induction chemotherapy was observed mainly in those high risk tumors with induced tumor cell differentiation features. Remarkably, these NB tumors showed good clinical response and prolonged patient survival. Conclusions: The neuron-specific protein CHD5 may represent a marker of outcome in NB that can be tested by conventional immunohistochemistry. Re-establishment of CHD5 expression induced by chemotherapy could be a surrogate marker of treatment response. C1 [Garcia, Idoia; Mayol, Gemma; Rodriguez, Eva; Casala, Carla; Galvan, Patricia; de Torres, Carmen; Mora, Jaume; Lavarino, Cinzia] Hosp St Joan de Deu, Fdn St Joan de Deu, Dev Tumor Biol Lab, Barcelona, Spain. [Sunol, Mariona] Hosp St Joan de Deu, Dept Pathol, Barcelona, Spain. [Gershon, Timothy R.] Univ N Carolina, Dept Neurol, Chapel Hill, NC USA. [Rios, Jose] Univ Autonoma Barcelona, Lab Biostat & Epidemiol, Clin Pharmacol Serv, IDIBAPS,Hosp Clin, E-08193 Barcelona, Spain. [Cheung, Nai-Kong V.] Mem Sloan Kettering Canc Ctr, Dept Pediat, New York, NY 10021 USA. [Kieran, Mark W.; George, Rani E.] Dana Farber Canc Inst, Div Pediat Hematol Oncol, Boston, MA USA. [Perez-Atayde, Antonio R.] Childrens Hosp Boston, Dept Pathol, Boston, MA USA. RP Mora, J (reprint author), Hosp St Joan de Deu, Fdn St Joan de Deu, Dev Tumor Biol Lab, Barcelona, Spain. EM jmora@hsjdbcn.org; clavarino@fsjd.org OI Kieran, Mark/0000-0003-2184-7692; Rios, Jose/0000-0002-0716-8784; Gershon, Timothy/0000-0001-7034-6400 FU Spanish Ministry of Health [PI070286]; Spanish Society against Cancer (Asociacion Espanola Contra el Cancer); Catalan government [2005SGR00605, 2006FI00404] FX Authors thank Dr. B. Spengler (Fordham University, New York) and Dr. N.K.V. Cheung (MSKCC, New York) for annotated NB cell lines; the Neural Tissue Bank (Hospital Clinic, Barcelona) for normal brain samples and the Department of Audiovisual Systems (HSJD, Barcelona) for technical assistance. This study was supported by grants from the Spanish Ministry of Health (PI070286), Spanish Society against Cancer (Asociacion Espanola Contra el Cancer, 2007), the Catalan government (2005SGR00605; 2006FI00404), and the generous donations from Margarita del Pozo and Alicia Pueyo Foundations. NR 34 TC 31 Z9 32 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1476-4598 J9 MOL CANCER JI Mol. Cancer PD OCT 15 PY 2010 VL 9 AR 277 DI 10.1186/1476-4598-9-277 PG 14 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 677RH UT WOS:000284009000001 PM 20950435 ER PT J AU Sharma, N Franco, RA Kuster, JK Mitchell, AA Fuchs, T Saunders-Pullman, R Raymond, D Brin, MF Blitzer, A Bressman, SB Ozelius, LJ AF Sharma, Nutan Franco, Ramon A., Jr. Kuster, John K. Mitchell, Adele A. Fuchs, Tania Saunders-Pullman, Rachel Raymond, Deborah Brin, Mitchell F. Blitzer, Andrew Bressman, Susan B. Ozelius, Laurie J. TI Genetic Evidence for an Association of the TOR1A Locus with Segmental/Focal Dystonia SO MOVEMENT DISORDERS LA English DT Article DE focal dystonia; segmental dystonia; torsinA; single nucleotide polymorphisms ID CERVICAL DYSTONIA; TORSION DYSTONIA; FOCAL DYSTONIA; ADULT-ONSET; IDIOPATHIC DYSTONIA; DYT1; BLEPHAROSPASM; SUSCEPTIBILITY; DISEASE; PROTEIN AB Polymorphisms in the TOR1A/TOR1B region have been implicated as being associated with primary focal and segmental dystonia. In a cohort of subjects with either focal or segmental dystonia affecting the face, larynx, neck, or arm, we report a strong association of a single nucleotide polymorphism (SNP), the deletion allele at the Mtdel SNP (rs3842225), and protection from focal dystonia. In contrast, we did not find an association of either allele at the D216H SNP (rs1801968) with focal or segmental dystonia in the same cohort. (C) 2010 Movement Disorder Society C1 [Sharma, Nutan; Kuster, John K.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Franco, Ramon A., Jr.] Massachusetts Eye & Ear Infirm, Dept Otolaryngol, Boston, MA 02114 USA. [Mitchell, Adele A.; Fuchs, Tania; Ozelius, Laurie J.] Beth Israel Deaconess Med Ctr, Dept Genet & Genom Sci, New York, NY 10003 USA. [Saunders-Pullman, Rachel; Raymond, Deborah; Bressman, Susan B.] Beth Israel Deaconess Med Ctr, Dept Neurol, New York, NY 10003 USA. [Brin, Mitchell F.] Univ Calif Irvine, Dept Neurol, Irvine, CA 92717 USA. [Brin, Mitchell F.] Allergan LLC, Irvine, CA USA. [Blitzer, Andrew] New York Ctr Voice & Swallowing Disorders, New York, NY USA. [Ozelius, Laurie J.] Mt Sinai Sch Med, Dept Neurol, New York, NY USA. RP Sharma, N (reprint author), 149 13th St,Room 6407, Charlestown, MA 02129 USA. EM nsharma@partners.org FU National Institute of Neurological Disorders and Stroke [P01NS037409]; Allergan, Inc.; Bachman Strauss Dystonia and Parkinson Foundation FX This work was supported by the National Institute of Neurological Disorders and Stroke research grant P01NS037409 (N.S. and L.J.O.), an unrestricted research grant from Allergan, Inc. (N.S.) and the Bachman Strauss Dystonia and Parkinson Foundation (L.O. and S.B.B.). NR 31 TC 19 Z9 20 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD OCT 15 PY 2010 VL 25 IS 13 BP 2183 EP 2187 DI 10.1002/mds.23225 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 665HV UT WOS:000283026900025 PM 20669276 ER PT J AU Naumann, M Carruthers, A Carruthers, J Aurora, SK Zafonte, R Abu-Shakra, S Boodhoo, T Miller-Messana, MA Demos, G James, L Beddingfield, F VanDenburgh, A Chapman, MA Brin, MF AF Naumann, Markus Carruthers, Alastair Carruthers, Jean Aurora, Sheena K. Zafonte, Ross Abu-Shakra, Susan Boodhoo, Terry Miller-Messana, Mary Ann Demos, George James, Lynn Beddingfield, Frederick VanDenburgh, Amanda Chapman, Mary Ann Brin, Mitchell F. TI Meta-Analysis of Neutralizing Antibody Conversion with OnabotulinumtoxinA (BOTOX (R)) Across Multiple Indications SO MOVEMENT DISORDERS LA English DT Article DE botulinum toxin; cervical dystonia; hyperhidrosis; facial aesthetics; spasticity; overactive bladder; immunogenicity; antigenicity; neutralizing antibodies ID TOXIN TYPE-A; PRIMARY AXILLARY HYPERHIDROSIS; PLACEBO-CONTROLLED TRIAL; CHRONIC DAILY HEADACHE; BOTULINUM TOXIN; DOUBLE-BLIND; PROPHYLACTIC TREATMENT; GLABELLAR LINES; CERVICAL DYSTONIA; MOUSE BIOASSAY AB This meta-analysis evaluated the frequency of neutralizing antibody (nAb) conversion with onabotulinumtoxinA (BOTOX (R); Allergan) across five studied indications. The analysis was based on large, controlled or prospective, open-label trials (durations 4 months to >= 2 years). Serum samples were analyzed for nAbs using the Mouse Protection Assay. Subjects who were antibody negative at baseline and had at least one analyzable postbaseline antibody assay result were included. The 16 clinical studies included 3,006 subjects; of these, 2,240 met the inclusion criteria for this analysis. Subjects received 1-15 treatments (mean 3.8 treatments) with onabotulinumtoxinA. Total doses per treatment cycle ranged from 10 or 20 units in glabellar lines to 20-500 units in cervical dystonia. The numbers of subjects who converted from an antibody-negative status at baseline to anti-body-positive status at any post-treatment time point were: cervical dystonia 4/312 (1.28%), glabellar lines 2/718 (0.28%), over-active bladder 0/22 (0%), post-stroke spasticity 1/317 (0.32%), and primary axillary hyperhidrosis 4/871 (0.46%). Across all indications, 11/2,240 subjects (0.49%) converted from antibody negative at baseline to positive at one or more post-treatment time points, but only three subjects became clinically unresponsive to onabotulinumtoxinA at some point following a positive assay. Based on these large trials, the frequency of antibody conversion after onabotulinumtoxinA treatment is very low, and infrequently leads to loss of efficacy. (C) 2010 Movement Disorder Society C1 [Naumann, Markus] Klinikum Augsburg Neurol Klin, Dept Neurol, D-86156 Augsburg, Bayern, Germany. [Carruthers, Alastair] Univ British Columbia, Dept Dermatol & Skin Sci, Vancouver, BC V5Z 1M9, Canada. [Carruthers, Jean] Univ British Columbia, Dept Ophthalmol & Visual Sci, Vancouver, BC V5Z 1M9, Canada. [Aurora, Sheena K.] Swedish Pain & Headache Ctr, Seattle, WA USA. [Zafonte, Ross] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Spaulding Rehabil Hosp, Boston, MA USA. [Abu-Shakra, Susan; Boodhoo, Terry; Miller-Messana, Mary Ann; Demos, George; James, Lynn; Beddingfield, Frederick; VanDenburgh, Amanda; Brin, Mitchell F.] Allergan Pharmaceut Inc, Irvine, CA USA. [Beddingfield, Frederick] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA. [Chapman, Mary Ann] Visage Commun, Mead, WA USA. [Brin, Mitchell F.] Univ Calif Irvine, Dept Neurol, Irvine, CA 92717 USA. RP Naumann, M (reprint author), Klinikum Augsburg Neurol Klin, Dept Neurol, Stenglinstr 2, D-86156 Augsburg, Bayern, Germany. EM markus.naumann@klinikum-augsburg.de FU Allergan, Inc., Irvine, CA, USA; Allergan; National Institutes of Health, National Institute on Disability and Rehabilitation Research, Department of Defense, and Food and Drug Administration; Advanced Bionics; Alexza; Capnia; GlaxoSmithKline; MAP Pharmaceuticals; Merck and Co; OrthoMcNeil; Neuraleve; Nupathe; Takeda FX This study was sponsored by Allergan, Inc., Irvine, CA, USA. The authors acknowledge the contribution of the individual study investigators and Allergan employees to the study designs and data analyses.; S. Abu-Shakra, T. Boodhoo, M. Miller-Messana, G. Demos, L. James, F. Beddingfield, A. VanDenburgh, and M. F. Brin are employed by Allergan and receive stock in the company as part of their compensation package. M. A. Chapman has received compensation from and owns stock in Allergan, and in the past 12 months has received compensation from Research Advocacy Network, TTC Group, and Global Marketing Perspectives. In the past 12 months, Alastair and Jean Carruthers have acted as consultants to Allergan, have received unrestricted educational grants from Allergan, have been consultants to and investigators for Merz GmbH and consultants to Bioform, Inc. They have also served as investigators on an Allergan-sponsored clinical trial, are shareholders in Allergan, are members of the Allergan Global Executive Council, and are Consultants to Allergan on Neurotoxins and Fillers. In the past year, Ross Zafonte has received funding from the National Institutes of Health, National Institute on Disability and Rehabilitation Research, Department of Defense, and Food and Drug Administration (orphan drug). In the past 2 years, Sheena Aurora has received grants and research support from Advanced Bionics, Alexza, Allergan, Capnia, GlaxoSmithKline, MAP Pharmaceuticals, Merck and Co, OrthoMcNeil, Neuraleve, Nupathe, and Takeda; has served as a consultant for Ortho-McNeil Pharmaceutical, Inc., Merck and Co., GlaxoSmithKline, Allergan, Neuraleve, Nupathe, MA; and has received honoraria from Merck and Co., GlaxoSmithKline, Kowa, NuPathe, and Ortho-McNeil Pharmaceutical, Inc. In the past year, Markus Naumann has been a speaker for Allergan, Ipsen, Orion Pharma, and Cephalon. NR 34 TC 55 Z9 58 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD OCT 15 PY 2010 VL 25 IS 13 BP 2211 EP 2218 DI 10.1002/mds.23254 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 665HV UT WOS:000283026900029 PM 20737546 ER PT J AU Ghosh, SS Kakunoori, S Augustinack, J Nieto-Castanon, A Kovelman, I Gaab, N Christodoulou, JA Triantafyllou, C Gabrieli, JDE Fischl, B AF Ghosh, Satrajit S. Kakunoori, Sita Augustinack, Jean Nieto-Castanon, Alfonso Kovelman, Ioulia Gaab, Nadine Christodoulou, Joanna A. Triantafyllou, Christina Gabrieli, John D. E. Fischl, Bruce TI Evaluating the validity of volume-based and surface-based brain image registration for developmental cognitive neuroscience studies in children 4 to 11 years of age SO NEUROIMAGE LA English DT Article ID HUMAN CEREBRAL-CORTEX; MAGNETIC-RESONANCE IMAGES; COORDINATE SYSTEM; CORTICAL SURFACE; GEOMETRICALLY ACCURATE; VISUAL-CORTEX; MRI DATA; SEGMENTATION; CYTOARCHITECTURE; RECONSTRUCTION AB Understanding the neurophysiology of human cognitive development relies on methods that enable accurate comparison of structural and functional neuroimaging data across brains from people of different ages. A fundamental question is whether the substantial brain growth and related changes in brain morphology that occur in early childhood permit valid comparisons of brain structure and function across ages. Here we investigated whether valid comparisons can be made in children from ages 4 to 11, and whether there are differences in the use of volume-based versus surface-based registration approaches for aligning structural landmarks across these ages. Regions corresponding to the calcarine sulcus, central sulcus, and Sylvian fissure in both the hemispheres were manually labeled on T1-weighted structural magnetic resonance images from 31 children ranging in age from 4.2 to 11.2 years old. Quantitative measures of shape similarity and volumetric-overlap of these manually labeled regions were calculated when brains were aligned using a 12-parameter affine transform, SPM's nonlinear normalization, a diffeomorphic registration (ANTS), and FreeSurfer's surface-based registration. Registration error for normalization into a common reference framework across participants in this age range was lower than commonly used functional imaging resolutions. Surface-based registration provided significantly better alignment of cortical landmarks than volume-based registration. In addition, registering children's brains to a common space does not result in an age-associated bias between older and younger children, making it feasible to accurately compare structural properties and patterns of brain activation in children from ages 4 to 11. (C) 2010 Elsevier Inc. All rights reserved. C1 [Ghosh, Satrajit S.] MIT, Elect Res Lab, Cambridge, MA 02139 USA. [Triantafyllou, Christina] MIT, McGovern Inst Brain Res, Athinoula A Martinos Brain Imaging Ctr, Cambridge, MA 02139 USA. [Kakunoori, Sita; Augustinack, Jean; Fischl, Bruce] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Kovelman, Ioulia] Univ Michigan, Ann Arbor, MI 48109 USA. [Gaab, Nadine] Childrens Hosp, Boston, MA 02115 USA. [Fischl, Bruce] MIT, Comp Sci & AI Lab, Cambridge, MA 02139 USA. [Gabrieli, John D. E.; Fischl, Bruce] MIT, Div Hlth Sci & Technol, Cambridge, MA 02139 USA. RP Ghosh, SS (reprint author), MIT, Elect Res Lab, Cambridge, MA 02139 USA. EM satra@mit.edu RI Triantafyllou, Christina/E-7724-2011; OI Ghosh, Satrajit/0000-0002-5312-6729; Kovelman, Ioulia/0000-0003-4287-6986 FU National Center for Research Resources [P41-RR14075, BIRN002, U24 RR021382]; National Institute for Biomedical Imaging and Bioengineering [R01EB006758, R03EB008673]; National Institute on Aging [AG02238]; National Institute for Neurological Disorders and Stroke [R01 NS052585-01]; National Institutes of Health through the NIH Roadmap for Medical Research [U54 EB005149]; Ellison Medical Foundation FX Support for this research was provided in part by the National Center for Research Resources (P41-RR14075, and the NCRR BIRN Morphometric Project BIRN002, U24 RR021382), the National Institute for Biomedical Imaging and Bioengineering (R01EB006758, R03EB008673), the National Institute on Aging (AG02238), the National Institute for Neurological Disorders and Stroke (R01 NS052585-01) as well as the Mental Illness and Neuroscience Discovery (MIND) Institute, and is part of the National Alliance for Medical Image Computing (NAMIC), funded by the National Institutes of Health through the NIH Roadmap for Medical Research, Grant U54 EB005149. Additional support was provided by The Autism & Dyslexia Project funded by the Ellison Medical Foundation. We would like to thank Dr. Arno Klein for discussions and suggestions. NR 50 TC 70 Z9 70 U1 5 U2 16 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD OCT 15 PY 2010 VL 53 IS 1 BP 85 EP 93 DI 10.1016/j.neuroimage.2010.05.075 PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 637LJ UT WOS:000280818900010 PM 20621657 ER PT J AU Yendiki, A Greve, DN Wallace, S Vangel, M Bockholt, J Mueller, BA Magnotta, V Andreasen, N Manoach, DS Gollub, RL AF Yendiki, Anastasia Greve, Douglas N. Wallace, Stuart Vangel, Mark Bockholt, Jeremy Mueller, Bryon A. Magnotta, Vince Andreasen, Nancy Manoach, Dara S. Gollub, Randy L. TI Multi-site characterization of an fMRI working memory paradigm: Reliability of activation indices SO NEUROIMAGE LA English DT Article DE fMRI; Multi-center studies; Reliability; SIRP ID DORSOLATERAL PREFRONTAL CORTEX; SCHIZOPHRENIC SUBJECTS; MULTICENTER FMRI; FUNCTIONAL MRI; BRAIN IMAGES; TEST-RETEST; ROBUST; REGISTRATION; REPRODUCIBILITY; OPTIMIZATION AB Neuroimaging studies are facilitated significantly when it is possible to recruit subjects and acquire data at multiple sites. However, the use of different scanners and acquisition protocols is a potential source of variability in multi-site data. In this work we present a multi-site study of the reliability of fMRI activation indices, where 10 healthy volunteers were scanned at 4 different sites while performing a working memory paradigm. Our results indicate that, even with different scanner manufacturers and field strengths, activation variability due to site differences is small compared to variability due to subject differences in this cognitive task, provided we choose an appropriate activation measure. (C) 2010 Elsevier Inc. All rights reserved. C1 [Yendiki, Anastasia; Greve, Douglas N.; Wallace, Stuart; Vangel, Mark; Manoach, Dara S.; Gollub, Randy L.] Harvard Univ, Sch Med, MGH,Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Wallace, Stuart; Manoach, Dara S.; Gollub, Randy L.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Vangel, Mark] Massachusetts Gen Hosp, Mallinkcrodt GCRC Biomed Imaging Core, Charlestown, MA USA. [Bockholt, Jeremy] Univ New Mexico, Albuquerque, NM 87131 USA. [Bockholt, Jeremy] Mind Res Network, Albuquerque, NM USA. [Mueller, Bryon A.] Univ Minnesota, Dept Psychiat, Minneapolis, MN 55455 USA. [Magnotta, Vince; Andreasen, Nancy] Univ Iowa, Iowa City, IA USA. RP Yendiki, A (reprint author), Harvard Univ, Sch Med, MGH,Dept Radiol, Athinoula A Martinos Ctr Biomed Imaging, 149 13th St, Charlestown, MA 02129 USA. EM ayendiki@nmr.mgh.harvard.edu OI Gollub, Randy L./0000-0002-9434-4044 FU NCRR NIH HHS [U24 RR021382] NR 29 TC 27 Z9 27 U1 1 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD OCT 15 PY 2010 VL 53 IS 1 BP 119 EP 131 DI 10.1016/j.neuroimage.2010.02.084 PG 13 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 637LJ UT WOS:000280818900013 PM 20451631 ER PT J AU Canault, M Certel, K Schatzberg, D Wagner, DD Hynes, RO AF Canault, Matthias Certel, Kaan Schatzberg, Daphne Wagner, Denisa D. Hynes, Richard O. TI The Lack of ADAM17 Activity during Embryonic Development Causes Hemorrhage and Impairs Vessel Formation SO PLOS ONE LA English DT Article ID NECROSIS-FACTOR-ALPHA; JUNCTIONAL ADHESION MOLECULE; CONVERTING-ENZYME; IN-VITRO; INFLAMMATORY RESPONSES; TUMOR ANGIOGENESIS; ENDOTHELIAL-CELLS; DEFICIENT MICE; GROWTH-FACTOR; NOTCH AB Background: ADAM17/TACE activity is important during embryonic development. We wished to investigate possible roles of this metalloprotease, focusing on vascular development. Methodology/Principal Findings: Mice mutant in the enzymatic activity of ADAM17 were examined at various stages of embryonic development for vascular pattern and integrity using markers for vessel wall cells. We observed hemorrhage and edema starting at embryonic day E14.5 and becoming more severe as development proceeded; prior to embryonic day E14.5, embryos appeared normal. Staining for PECAM-1/CD31 revealed abnormalities in the patterns of branching of the embryonic vasculature at E14.5. Conclusions/Significance: These abnormalities preceded association of pericytes or monocyte/macrophage cells with the affected vessels and, therefore, presumably arise from defects in endothelial function consequent upon failure of ADAM17 to cleave one or more substrates involved in vascular development, such as Notch, Delta, VEGFR2 or JAM-A. Our study demonstrates a role for ADAM17 in modulating embryonic vessel development and function. C1 [Canault, Matthias; Schatzberg, Daphne; Wagner, Denisa D.] Immune Dis Inst, Boston, MA USA. [Canault, Matthias; Schatzberg, Daphne; Wagner, Denisa D.] Childrens Hosp, Program Cellular & Mol Med, Boston, MA 02115 USA. [Canault, Matthias; Wagner, Denisa D.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Certel, Kaan; Hynes, Richard O.] Howard Hughes Med Inst, Chevy Chase, MA USA. [Certel, Kaan; Hynes, Richard O.] MIT, David H Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. RP Canault, M (reprint author), Immune Dis Inst, Boston, MA USA. EM wagner@idi.harvard.edu; rohynes@mit.edu RI Canault, Matthias/H-5128-2013 OI Canault, Matthias/0000-0002-7880-5250 FU National Heart, Lung, and Blood Institute of the National Institutes of Health [P01 HL066105, P01 HL056949]; Howard Hughes Medical Institute FX This work was supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health grants P01 HL066105 (D. D. W. and R.O.H.) and P01 HL056949 (D. D. W.) and support from the Howard Hughes Medical Institute, of which R.O.H. is an investigator. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 31 TC 15 Z9 16 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD OCT 15 PY 2010 VL 5 IS 10 AR e13433 DI 10.1371/journal.pone.0013433 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 665NX UT WOS:000283043700022 PM 20976179 ER PT J AU Pasquet, A Messou, E Gabillard, D Minga, A Depoulosky, A Deuffic-Burban, S Losina, E Freedberg, KA Danel, C Anglaret, X Yazdanpanah, Y AF Pasquet, Armelle Messou, Eugene Gabillard, Delphine Minga, Albert Depoulosky, Ayeby Deuffic-Burban, Sylvie Losina, Elena Freedberg, Kenneth A. Danel, Christine Anglaret, Xavier Yazdanpanah, Yazdan TI Impact of Drug Stock-Outs on Death and Retention to Care among HIV-Infected Patients on Combination Antiretroviral Therapy in Abidjan, Cote d'Ivoire SO PLOS ONE LA English DT Article ID RESOURCE-POOR SETTINGS; SUB-SAHARAN AFRICA; HIV-1-INFECTED PATIENTS; INCOME COUNTRIES; SOUTH-AFRICA; SCALING-UP; COHORT; ADHERENCE; DETERMINANTS; MORTALITY AB Background: To evaluate the type and frequency of antiretroviral drug stock-outs, and their impact on death and interruption in care among HIV-infected patients in Abidjan, Cote d'Ivoire. Methods and Findings: We conducted a cohort study of patients who initiated combination antiretroviral therapy (cART) in three adult HIV clinics between February 1, 2006 and June 1, 2007. Follow-up ended on February 1, 2008. The primary outcome was cART regimen modification, defined as at least one drug substitution, or discontinuation for at least one month due to drug stock-outs at the clinic pharmacy. The secondary outcome for patients who were on cART for at least six months was interruption in care, or death. A Cox regression model with time-dependent variables was used to assess the impact of antiretroviral drug stock-outs on interruption in care or death. Overall, 1,554 adults initiated cART and were followed for a mean of 13.2 months. During this time, 72 patients discontinued treatment and 98 modified their regimen because of drug stock-outs. Stock-outs involved nevirapine and fixed-dose combination zidovudine/lamivudine in 27% and 51% of cases. Of 1,554 patients, 839 (54%) initiated cART with fixed-dose stavudine/lamivudine/nevirapine and did not face stock-outs during the study period. Among the 975 patients who were on cART for at least six months, stock-out-related cART discontinuations increased the risk of interruption in care or death (adjusted hazard ratio [HR], 2.83; 95%CI, 1.25-6.44) but cART modifications did not (adjusted HR, 1.21; 95%CI, 0.46-3.16). Conclusions: cART stock-outs affected at least 11% of population on treatment. Treatment discontinuations due to stock-outs were frequent and doubled the risk of interruption in care or death. These stock-outs did not involve the most common first-line regimen. As access to cART continues to increase in sub-Saharan Africa, first-line regimens should be standardized to decrease the probability of drug stock-outs. C1 [Pasquet, Armelle; Yazdanpanah, Yazdan] Ctr Hosp Tourcoing, Serv Univ Malad Infect & Voyageur, Tourcoing, France. [Messou, Eugene; Depoulosky, Ayeby] Programme Aconda, Abidjan, Cote Ivoire. [Gabillard, Delphine; Minga, Albert; Danel, Christine; Anglaret, Xavier] INSERM, U897, Bordeaux, France. [Minga, Albert; Danel, Christine; Anglaret, Xavier] Programme PACCI, Abidjan, Cote Ivoire. [Deuffic-Burban, Sylvie] INSERM, U995, Lille, France. [Deuffic-Burban, Sylvie; Yazdanpanah, Yazdan] Fac Med Lille, EA 2694, Lille, France. [Losina, Elena; Freedberg, Kenneth A.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Pasquet, A (reprint author), Ctr Hosp Tourcoing, Serv Univ Malad Infect & Voyageur, Tourcoing, France. EM armellepasquet@hotmail.com RI Anglaret, Xavier/F-7333-2013 FU Agence Nationale de Recherches sur le SIDA et les patites virales; National Institute of Allergy and Infectious Diseases [K24 AI062476, R01 AI058736]; Boehringer-Ingelheim; Bristol-Myers Squibb; Gilead Sciences; Glaxo-SmithKline; Merck-Sharp and Dohme-Chibret; Pfizer; Roche; Schering Plough; Tibotec; Janssen-Cilag FX This work was supported in part by the Agence Nationale de Recherches sur le SIDA et les patites virales; and the National Institute of Allergy and Infectious Diseases K24 AI062476 and R01 AI058736. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.; With the exception of Yazdan Yazdanpanah and Sylvie Deuffic-Burban none of the authors report any association that might pose a conflict of interest. Dr. Yazdanpanah has received travel grants, consultancy fees and honoraria for presentation at workshops from Boehringer-Ingelheim, Bristol-Myers Squibb, Gilead Sciences, Glaxo-SmithKline, Merck-Sharp and Dohme-Chibret, Pfizer, Roche, Schering Plough and Tibotec. Mrs. Deuffic-Burban has received grants from Roche and Janssen-Cilag. This does not alter the authors' adherence to all the PLoS ONE policies on sharing data and materials. NR 38 TC 45 Z9 45 U1 1 U2 6 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD OCT 15 PY 2010 VL 5 IS 10 AR e13414 DI 10.1371/journal.pone.0013414 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 665NX UT WOS:000283043700014 PM 20976211 ER PT J AU Srikanth, CV Wall, DM Maldonado-Contreras, A Shi, HN Zhou, DG Demma, Z Mumy, KL McCormick, BA AF Srikanth, C. V. Wall, Daniel M. Maldonado-Contreras, Ana Shi, Hai Ning Zhou, Daoguo Demma, Zachary Mumy, Karen L. McCormick, Beth A. TI Salmonella Pathogenesis and Processing of Secreted Effectors by Caspase-3 SO SCIENCE LA English DT Article ID EPITHELIAL-CELLS; TYPHIMURIUM; PROTEIN; INVASION; ACTIN; IDENTIFICATION; FILAMENTS; ABILITY; GROWTH; DOMAIN AB The enteric pathogen Salmonella enterica serovar Typhimurium causes food poisoning resulting in gastroenteritis. The S. Typhimurium effector Salmonella invasion protein A (SipA) promotes gastroenteritis by functional motifs that trigger either mechanisms of inflammation or bacterial entry. During infection of intestinal epithelial cells, SipA was found to be responsible for the early activation of caspase-3, an enzyme that is required for SipA cleavage at a specific recognition motif that divided the protein into its two functional domains and activated SipA in a manner necessary for pathogenicity. Other caspase-3 cleavage sites identified in S. Typhimurium appeared to be restricted to secreted effector proteins, which indicates that this may be a general strategy used by this pathogen for processing of its secreted effectors. C1 [Srikanth, C. V.; Wall, Daniel M.; Shi, Hai Ning; Mumy, Karen L.; McCormick, Beth A.] Harvard Univ, Sch Med, Dept Pediat Gastroenterol & Nutr, Boston, MA 02129 USA. [Srikanth, C. V.; Wall, Daniel M.; Shi, Hai Ning; Mumy, Karen L.; McCormick, Beth A.] Massachusetts Gen Hosp, Boston, MA 02129 USA. [Srikanth, C. V.; Maldonado-Contreras, Ana; Demma, Zachary; Mumy, Karen L.; McCormick, Beth A.] Univ Massachusetts, Sch Med, Dept Mol Genet & Microbiol, Worcester, MA 01655 USA. [Wall, Daniel M.] Univ Glasgow, Coll Med Vet & Life Sci, Inst Infect Immun & Inflammat, Glasgow G12 8QQ, Lanark, Scotland. [Zhou, Daoguo] Purdue Univ, Dept Biol Sci, W Lafayette, IN 47907 USA. RP McCormick, BA (reprint author), Harvard Univ, Sch Med, Dept Pediat Gastroenterol & Nutr, Boston, MA 02129 USA. EM Beth.McCormick@umassmed.edu FU NIH [DK56754, DK33506]; Crohn's and Colitis Foundation of America; Tenovus Scotland; Society for General Microbiology FX The research was supported by grants from the NIH (DK56754 and DK33506) and the Crohn's and Colitis Foundation of America to B. A. M. Additional grant support was provided by Tenovus Scotland and a Society for General Microbiology travel award to D. M. W. The use of human volunteers in this study was in accordance with appropriate guidelines and was approved by the University of Massachusetts Medical School Review Board for the Protection of Human Subjects (approval no. 13006). NR 22 TC 51 Z9 53 U1 4 U2 23 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD OCT 15 PY 2010 VL 330 IS 6002 BP 390 EP 393 DI 10.1126/science.1194598 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 664TY UT WOS:000282986700046 PM 20947770 ER PT J AU Mann, G Attarbaschi, A Schrappe, M De Lorenzo, P Peters, C Hann, I De Rossi, G Felice, M Lausen, B LeBlanc, T Szczepanski, T Ferster, A Janka-Schaub, G Rubnitz, J Silverman, LB Stary, J Campbell, M Li, CK Suppiah, R Biondi, A Vora, A Valsecchi, MG Pieters, R AF Mann, Georg Attarbaschi, Andishe Schrappe, Martin De Lorenzo, Paola Peters, Christina Hann, Ian De Rossi, Giulio Felice, Maria Lausen, Birgitte LeBlanc, Thierry Szczepanski, Tomasz Ferster, Alina Janka-Schaub, Gritta Rubnitz, Jeffrey Silverman, Lewis B. Stary, Jan Campbell, Myriam Li, Chi Kong Suppiah, Ram Biondi, Andrea Vora, Ajay Valsecchi, Maria Grazia Pieters, Rob CA Interfant-99 Study Grp TI Improved outcome with hematopoietic stem cell transplantation in a poor prognostic subgroup of infants with mixed-lineage-leukemia (MLL)-rearranged acute lymphoblastic leukemia: results from the Interfant-99 Study SO BLOOD LA English DT Article ID MINIMAL RESIDUAL DISEASE; GENE REARRANGEMENTS; CHEMOTHERAPY; CHILDREN; SURVIVAL; PROTOCOL; YOUNGER AB To define a role for hematopoietic stem cell transplantation (HSCT) in infants with acute lymphoblastic leukemia and rearrangements of the mixed-lineage-leukemia gene (MLL+), we compared the outcome of MLL+ patients from trial Interfant-99 who either received chemotherapy only or HSCT. Of 376 patients with a known MLL status in the trial, 297 (79%) were MLL+. Among the 277 of 297 MLL+ patients (93%) in first remission (CR), there appeared to be a significant difference in disease-free survival (adjusted by waiting time to HSCT) between the 37 (13%) who received HSCT and the 240 (87%) who received chemotherapy only (P = .03). However, the advantage was restricted to a subgroup with 2 additional unfavorable prognostic features: age less than 6 months and either poor response to steroids at day 8 or leukocytes more than or equal to 300 g/L. Ninety-seven of 297 MLL+ patients (33%) had such high-risk criteria, with 87 achieving CR. In this group, HSCT was associated with a 64% reduction in the risk of failure resulting from relapse or death in CR (hazard ratio = 0.36, 95% confidence interval, 0.15-0.86). In the remaining patients, there was no advantage for HSCT over chemotherapy only. In summary, HSCT seems to be a valuable option for a subgroup of infant MLL+ acute lymphoblastic leukemia carrying further poor prognostic factors. The trial was registered at www.clinicaltrials.gov as #NCT00015873 and at www.controlled-trials.com as #ISRCTN24251487. (Blood. 2010;116(15):2644-2650) C1 [Schrappe, Martin] Berlin Frankfurt Munster Study Grp, Berlin, Germany. [De Lorenzo, Paola; Valsecchi, Maria Grazia] Univ Milano Bicocca, Dept Clin Med & Prevent, Interfant Trial Data Ctr, Milan, Italy. [Felice, Maria] Argentinean Grp Pediat Hematol & Oncol, Buenos Aires, DF, Argentina. [Rubnitz, Jeffrey] St Jude Childrens Hosp, Memphis, TN 38105 USA. [Silverman, Lewis B.] Dana Farber Canc Inst ALL Consortium, Boston, MA USA. [Campbell, Myriam] Programa Infantil Nacl Drogas Antineoplas, Santiago, Chile. [Li, Chi Kong] Hong Kong Pediat Hematol & Oncol Study Grp, Hong Kong, Hong Kong, Peoples R China. [Pieters, Rob] Erasmus MC Sophia Childrens Hosp, Dutch Childhood Oncol Study Grp, NL-3015GJ Rotterdam, Netherlands. RP Mann, G (reprint author), St Anna Childrens Hosp, Dept Pediat Oncol & Hematol, Kinderspitalgasse 6, A-1090 Vienna, Austria. EM georg.mann@stanna.at; rob.pieters@erasmusmc.nl RI Li, Chi Kong/J-8456-2013 FU Associazione Italiana Ricerca sul Cancro [1105]; Fondazione Tettamanti and Comitato ML Verga; St Anna Kinderkrebsforschung; Deutsche Krebshilfe; Czech Ministry of Education [MSM0021620813]; Polish Ministry of Science and Higher Education [2 P054 095 30] FX The Associazione Italiana Ematologia Oncologia Pediatrica was supported by the Associazione Italiana Ricerca sul Cancro (Regional Grant Code 1105; A.B., M.G.V.) and the international trial center by the Fondazione Tettamanti and Comitato ML Verga (M.G.V., P.D.L.). The Berlin-Frankfurt-Munster Study Group-Austria was supported by the St Anna Kinderkrebsforschung, Berlin-Frankfurt-Munster Study Group-Germany by the Deutsche Krebshilfe, the Czech Pediatric Haematology by the Czech Ministry of Education (grant MSM0021620813), and the Polish Pediatric Leukemia and Lymphoma Study Group (grant 2 P054 095 30) by the Polish Ministry of Science and Higher Education (T.S.). NR 31 TC 46 Z9 50 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD OCT 14 PY 2010 VL 116 IS 15 BP 2644 EP 2650 DI 10.1182/blood-2010-03-273532 PG 7 WC Hematology SC Hematology GA 664JR UT WOS:000282956700010 PM 20592248 ER PT J AU Deng, XM Okram, B Ding, QA Zhang, JM Choi, YM Adrian, FJ Wojciechowski, A Zhang, GB Che, JW Bursulaya, B Cowan-Jacob, SW Rummel, G Sim, T Gray, NS AF Deng, Xianming Okram, Barun Ding, Qiang Zhang, Jianming Choi, Yongmun Adrian, Francisco J. Wojciechowski, Amy Zhang, Guobao Che, Jianwei Bursulaya, Badry Cowan-Jacob, Sandra W. Rummel, Gabriele Sim, Taebo Gray, Nathanael S. TI Expanding the Diversity of Allosteric Ber-Abl Inhibitors SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID CHRONIC MYELOGENOUS LEUKEMIA; KINASE DOMAIN MUTANTS; BCR-ABL; QUANTITATIVE-ANALYSIS; PHOSPHATIDIC-ACID; RESISTANCE; IMATINIB; PYRIMIDINES; IDENTIFICATION; MECHANISMS AB Inhibition of Bcr-Abl kinase activity by imatinib for the treatment of chronic myeloid leukemia (CM I.) currently serves as the paradigm or targeting dominant oncogenes with small molecules. We recently reported the discovery of GNF (1) and GNF (2) as selective non-ATP competitive inhibitors of cellular Bcr-Abl kinase activity that target the myristate binding site. Here, we used cell-based structure-activity relationships to guide the optimization and diversification of ligands that are capable of binding to the myristate binding site and rationalize the findings based upon an Abl-compound 1 cocrystal. We elucidate the structure-activity relationships required to obtain potent antiproliferative activity against Bcr-Abl transformed cells and report the discovery of new compounds (544, 5h, 6a, 14d, and 21j-1) that display improved potency or pharmacological properties. This work demonstrates that a variety of structures can effectively target the myristate binding site and provides new leads for developing drugs that can target this binding site. C1 [Sim, Taebo] Korea Inst Sci & Technol, Life Hlth Div, Seoul 136791, South Korea. [Deng, Xianming; Zhang, Jianming; Choi, Yongmun; Wojciechowski, Amy; Gray, Nathanael S.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Deng, Xianming; Zhang, Jianming; Choi, Yongmun; Wojciechowski, Amy; Gray, Nathanael S.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Okram, Barun] Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA. [Ding, Qiang; Adrian, Francisco J.; Zhang, Guobao; Che, Jianwei; Bursulaya, Badry] Novartis Res Fdn, Genom Inst, Dept Biol Chem, San Diego, CA 92121 USA. [Rummel, Gabriele] Novartis Inst Biomed Res, CH-4002 Basel, Switzerland. RP Sim, T (reprint author), Korea Inst Sci & Technol, Life Hlth Div, 39-1 Hawolgok Dong,Wolsong Gil5, Seoul 136791, South Korea. EM tbsim@kist.re.kr; nathanael_gray@dfci.harvard.edu FU Novartis; NIH [R01 CA 130876-02] FX We thank the members from Nathanael S. Gray laboratory for experimental assistance and insightful comments throughout this study. Some of the cellular and biochemical assays were performed at the ICCB at Harvard Medical School with help from Andrew Daab. Sean M.Johnson, and Stewart Rudnicki. The Gray laboratory acknowledges the generous financial support from Novartis and NIH Grant R01 CA 130876-02 and useful discussions with Michael lick. Markus Warmuth, Paul Manley. Doriano Fabbro and John Engen. NR 33 TC 32 Z9 32 U1 1 U2 13 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD OCT 14 PY 2010 VL 53 IS 19 BP 6934 EP 6946 DI 10.1021/jm100555f PG 13 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 659CO UT WOS:000282544800011 PM 20828158 ER PT J AU Liu, QS Chang, JW Wang, JH Kang, SA Thoreen, CC Markhard, A Hur, W Zhang, JM Sim, T Sabatini, DM Gray, NS AF Liu, Qingsong Chang, Jae Won Wang, Jinhua Kang, Seong A. Thoreen, Carson C. Markhard, Andrew Hur, Wooyoung Zhang, Jianming Sim, Taebo Sabatini, David M. Gray, Nathanael S. TI Discovery of 1-(4-(4-Propionylpiperazin-1-yl)-3-(trifluoromethyl)phenyl)-9-(quinolin- 3-yl)benzo[h][1,6]naphthyridin-2(1H)-one as a Highly Potent, Selective Mammalian Target of Rapamycin (mTOR) Inhibitor for the Treatment of Cancer SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID VIVO ANTITUMOR-ACTIVITY; TYROSINE KINASE; SITE INHIBITORS; SCAFFOLD; IDENTIFICATION; NVP-BEZ235; PATHWAYS; GROWTH; PI3K AB The mTOR It protein is a master regulator of cell growth and proliferation, and inhibitors of its kinase activity have the potential to become new class of anticancer drugs. Starting from quinoline I, which was identified in a biochemical mTOR assay, we developed a tricyclic benzonaphthyridinone inhibitor 37 (Torin 1), which inhibited phosphorylation of mTORC1 and mTORC2 substrates in cells at concentrations of 2 and 10 nM, respectively. Moreover, Torin I exhibits 1000-fold selectivity for mTOR over P13K (EC(50) = 1800 nM) and exhibits 100-fold binding selectivity relative to 450 other protein kinases. Torin was efficacious at a dose of 20 mg/kg in a U87MG xenograft model and demonstrated good pharmacodynamic inhibition of downstream effectors of mTOR in tumor and per tissues. These results demonstrate that Torin I is a useful probe of mTOR-dependent phenomena and that benzo-naphthridinones represent a promising scaffold for the further development of mTOR-specific inhibitors with the potential for clinical utility. C1 [Liu, Qingsong; Chang, Jae Won; Wang, Jinhua; Thoreen, Carson C.; Hur, Wooyoung; Zhang, Jianming; Sim, Taebo; Gray, Nathanael S.] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Liu, Qingsong; Chang, Jae Won; Wang, Jinhua; Thoreen, Carson C.; Hur, Wooyoung; Zhang, Jianming; Sim, Taebo; Gray, Nathanael S.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Kang, Seong A.; Markhard, Andrew; Sabatini, David M.] Whitehead Inst Biomed Res, Cambridge Ctr 9, Cambridge, MA 02142 USA. [Sabatini, David M.] MIT, Dept Biol, Howard Hughes Med Inst, Cambridge, MA 02139 USA. [Sabatini, David M.] MIT, Coch Ctr Integrat Res, Cambridge, MA 02139 USA. RP Gray, NS (reprint author), Dana Farber Canc Inst, Dept Canc Biol, 44 Binney St, Boston, MA 02115 USA. EM Nathanael_gray@dcfi.harvard.edu OI liu, qing song/0000-0002-7829-2547 FU NCI NIH HHS [R01 CA103866, R01 CA129105, R01 CA129105-04]; NIA NIH HHS [R21 AG042876]; NIAID NIH HHS [R37 AI047389] NR 35 TC 91 Z9 92 U1 2 U2 21 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD OCT 14 PY 2010 VL 53 IS 19 BP 7146 EP 7155 DI 10.1021/jm101144f PG 10 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 659CO UT WOS:000282544800030 PM 20860370 ER PT J AU Heinrich, MC Corless, CL AF Heinrich, Michael C. Corless, Christopher L. TI CANCER Oncogenes in context SO NATURE LA English DT Editorial Material ID GASTROINTESTINAL STROMAL TUMORS C1 [Heinrich, Michael C.] Portland VA Med Ctr, Dept Med, Portland, OR 97239 USA. [Corless, Christopher L.] Portland VA Med Ctr, Dept Pathol, Portland, OR 97239 USA. OHSU Knight Canc Inst, Portland, OR 97239 USA. RP Heinrich, MC (reprint author), Portland VA Med Ctr, Dept Med, Portland, OR 97239 USA. EM heinrich@ohsu.edu NR 11 TC 5 Z9 5 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD OCT 14 PY 2010 VL 467 IS 7317 BP 796 EP 797 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 663PB UT WOS:000282898700053 PM 20944735 ER PT J AU Allen, HL Estrada, K Lettre, G Berndt, SI Weedon, MN Rivadeneira, F Willer, CJ Jackson, AU Vedantam, S Raychaudhuri, S Ferreira, T Wood, AR Weyant, RJ Segre, AV Speliotes, EK Wheeler, E Soranzo, N Park, JH Yang, J Gudbjartsson, D Heard-Costa, NL Randall, JC Qi, L Smith, AV Magi, R Pastinen, T Liang, L Heid, IM Luan, J Thorleifsson, G Winkler, TW Goddard, ME Lo, KS Palmer, C Workalemahu, T Aulchenko, YS Johansson, A Zillikens, MC Feitosa, MF Esko, T Johnson, T Ketkar, S Kraft, P Mangino, M Prokopenko, I Absher, D Albrecht, E Ernst, F Glazer, NL Hayward, C Hottenga, JJ Jacobs, KB Knowles, JW Kutalik, Z Monda, KL Polasek, O Preuss, M Rayner, NW Robertson, NR Steinthorsdottir, V Tyrer, JP Voight, BF Wiklund, F Xu, JF Zhao, JH Nyholt, DR Pellikka, N Perola, M Perry, JRB Surakka, I Tammesoo, ML Altmaier, EL Amin, N Aspelund, T Bhangale, T Boucher, G Chasman, DI Chen, C Coin, L Cooper, MN Dixon, AL Gibson, Q Grundberg, E Hao, K Junttila, MJ Kaplan, LM Kettunen, J Konig, IR Kwan, T Lawrence, RW Levinson, DF Lorentzon, M McKnight, B Morris, AP Muller, M Ngwa, JS Purcell, S Rafelt, S Salem, RM Salvi, E Sanna, S Shi, JX Sovio, U Thompson, JR Turchin, MC Vandenput, L Verlaan, DJ Vitart, V White, CC Ziegler, A Almgren, P Balmforth, AJ Campbell, H Citterio, L De Grandi, A Dominiczak, A Duan, J Elliott, P Elosua, R Eriksson, JG Freimer, NB Geus, EJC Glorioso, N Haiqing, S Hartikainen, AL Havulinna, AS Hicks, AA Hui, JN Igl, W Illig, T Jula, A Kajantie, E Kilpelaeinen, TO Koiranen, M Kolcic, I Koskinen, S Kovacs, P Laitinen, J Liu, JJ Lokki, ML Marusic, A Maschio, A Meitinger, T Mulas, A Pare, G Parker, AN Peden, JF Petersmann, A Pichler, I Pietilainen, KH Pouta, A Riddertrale, M Rotter, JI Sambrook, JG Sanders, AR Schmidt, CO Sinisalo, J Smit, JH Stringham, HM Walters, GB Widen, E Wild, SH Willemsen, G Zagato, L Zgaga, L Zitting, P Alavere, H Farrall, M McArdle, WL Nelis, M Peters, MJ Ripatti, S Meurs, JBJ Aben, KK Ardlie, KG Beckmann, JS Beilby, JP Bergman, RN Bergmann, S Collins, FS Cusi, D den Heijer, M Eiriksdottir, G Gejman, PV Hall, AS Hamsten, A Huikuri, HV Iribarren, C Kahonen, M Kaprio, J Kathiresan, S Kiemeney, L Kocher, T Launer, LJ Lehtimaki, T Melander, O Mosley, TH Musk, AW Nieminen, MS O'Donnell, CJ Ohlsson, C Oostra, B Palmer, LJ Raitakari, O Ridker, PM Rioux, JD Rissanen, A Rivolta, C Schunkert, H Shuldiner, AR Siscovick, DS Stumvoll, M Tonjes, A Tuomilehto, J van Ommen, GJ Viikari, J Heath, AC Martin, NG Montgomery, GW Province, MA Kayser, M Arnold, AM Atwood, LD Boerwinkle, E Chanock, SJ Deloukas, P Gieger, C Gronberg, H Hall, P Hattersley, AT Hengstenberg, C Hoffman, W Lathrop, GM Salomaa, V Schreiber, S Uda, M Waterworth, D Wright, AF Assimes, TL Barroso, I Hofman, A Mohlke, KL Boomsma, DI Caulfield, MJ Cupples, LA Erdmann, J Fox, CS Gudnason, V Gyllensten, U Harris, TB Hayes, RB Jarvelin, MR Mooser, V Munroe, PB Ouwehand, WH Penninx, BW Pramstaller, PP Quertermous, T Rudan, I Samani, NJ Spector, TD Volzke, H Watkins, H Wilson, JF Groop, LC Haritunians, T Hu, FB Kaplan, RC Metspalu, A North, KE Schlessinger, D Wareham, NJ Hunter, DJ O'Connell, JR Strachan, DP Schadt, HE Thorsteinsdottir, U Peltonen, L Uitterlinden, AG Visscher, PM Chatterjee, N Loos, RJF Boehnke, M McCarthy, MI Ingelsson, E Lindgren, CM Abecasis, GR Stefansson, K Frayling, TM Hirschhorn, JN AF Allen, Hana Lango Estrada, Karol Lettre, Guillaume Berndt, Sonja I. Weedon, Michael N. Rivadeneira, Fernando Willer, Cristen J. Jackson, Anne U. Vedantam, Sailaja Raychaudhuri, Soumya Ferreira, Teresa Wood, Andrew R. Weyant, Robert J. Segre, Ayellet V. Speliotes, Elizabeth K. Wheeler, Eleanor Soranzo, Nicole Park, Ju-Hyun Yang, Jian Gudbjartsson, Daniel Heard-Costa, Nancy L. Randall, Joshua C. Qi, Lu Smith, Albert Vernon Maegi, Reedik Pastinen, Tomi Liang, Liming Heid, Iris M. Luan, Jian'an Thorleifsson, Gudmar Winkler, Thomas W. Goddard, Michael E. Lo, Ken Sin Palmer, Cameron Workalemahu, Tsegaselassie Aulchenko, Yurii S. Johansson, Asa Zillikens, M. Carola Feitosa, Mary F. Esko, Tonu Johnson, Toby Ketkar, Shamika Kraft, Peter Mangino, Massimo Prokopenko, Inga Absher, Devin Albrecht, Eva Ernst, Florian Glazer, Nicole L. Hayward, Caroline Hottenga, Jouke-Jan Jacobs, Kevin B. Knowles, Joshua W. Kutalik, Zoltan Monda, Keri L. Polasek, Ozren Preuss, Michael Rayner, Nigel W. Robertson, Neil R. Steinthorsdottir, Valgerdur Tyrer, Jonathan P. Voight, Benjamin F. Wiklund, Fredrik Xu, Jianfeng Zhao, Jing Hua Nyholt, Dale R. Pellikka, Niina Perola, Markus Perry, John R. B. Surakka, Ida Tammesoo, Mari-Liis Altmaier, Elizabeth L. Amin, Najaf Aspelund, Thor Bhangale, Tushar Boucher, Gabrielle Chasman, Daniel I. Chen, Constance Coin, Lachlan Cooper, Matthew N. Dixon, Anna L. Gibson, Quince Grundberg, Elin Hao, Ke Junttila, M. Juhani Kaplan, Lee M. Kettunen, Johannes Koenig, Inke R. Kwan, Tony Lawrence, Robert W. Levinson, Douglas F. Lorentzon, Mattias McKnight, Barbara Morris, Andrew P. Mueller, Martina Ngwa, Julius Suh Purcell, Shaun Rafelt, Suzanne Salem, Rany M. Salvi, Erika Sanna, Serena Shi, Jianxin Sovio, Ulla Thompson, John R. Turchin, Michael C. Vandenput, Liesbeth Verlaan, Dominique J. Vitart, Veronique White, Charles C. Ziegler, Andreas Almgren, Peter Balmforth, Anthony J. Campbell, Harry Citterio, Lorena De Grandi, Alessandro Dominiczak, Anna Duan, Jubao Elliott, Paul Elosua, Roberto Eriksson, Johan G. Freimer, Nelson B. Geus, Eco J. C. Glorioso, Nicola Haiqing, Shen Hartikainen, Anna-Liisa Havulinna, Aki S. Hicks, Andrew A. Hui, Jennie Igl, Wilmar Illig, Thomas Jula, Antti Kajantie, Eero Kilpelaeinen, Tuomas O. Koiranen, Markku Kolcic, Ivana Koskinen, Seppo Kovacs, Peter Laitinen, Jaana Liu, Jianjun Lokki, Marja-Liisa Marusic, Ana Maschio, Andrea Meitinger, Thomas Mulas, Antonella Pare, Guillaume Parker, Alex N. Peden, John F. Petersmann, Astrid Pichler, Irene Pietilainen, Kirsi H. Pouta, Anneli Riddertrale, Martin Rotter, Jerome I. Sambrook, Jennifer G. Sanders, Alan R. Schmidt, Carsten Oliver Sinisalo, Juha Smit, Jan H. Stringham, Heather M. Walters, G. Bragi Widen, Elisabeth Wild, Sarah H. Willemsen, Gonneke Zagato, Laura Zgaga, Lina Zitting, Paavo Alavere, Helene Farrall, Martin McArdle, Wendy L. Nelis, Mari Peters, Marjolein J. Ripatti, Samuli vVan Meurs, Joyce B. J. Aben, Katja K. Ardlie, Kristin G. Beckmann, Jacques S. Beilby, John P. Bergman, Richard N. Bergmann, Sven Collins, Francis S. Cusi, Daniele den Heijer, Martin Eiriksdottir, Gudny Gejman, Pablo V. Hall, Alistair S. Hamsten, Anders Huikuri, Heikki V. Iribarren, Carlos Kahonen, Mika Kaprio, Jaakko Kathiresan, Sekar Kiemeney, Lambertus Kocher, Thomas Launer, Lenore J. Lehtimaki, Terho Melander, Olle Mosley, Tom H., Jr. Musk, Arthur W. Nieminen, Markku S. O'Donnell, Christopher J. Ohlsson, Claes Oostra, Ben Palmer, Lyle J. Raitakari, Olli Ridker, Paul M. Rioux, John D. Rissanen, Aila Rivolta, Carlo Schunkert, Heribert Shuldiner, Alan R. Siscovick, David S. Stumvoll, Michael Toenjes, Anke Tuomilehto, Jaakko van Ommen, Gert-Jan Viikari, Jorma Heath, Andrew C. Martin, Nicholas G. Montgomery, Grant W. Province, Michael A. Kayser, Manfred Arnold, Alice M. Atwood, Larry D. Boerwinkle, Eric Chanock, Stephen J. Deloukas, Panos Gieger, Christian Gronberg, Henrik Hall, Per Hattersley, Andrew T. Hengstenberg, Christian Hoffman, Wolfgang Lathrop, G. Mark Salomaa, Veikko Schreiber, Stefan Uda, Manuela Waterworth, Dawn Wright, Alan F. Assimes, Themistocles L. Barroso, Ines Hofman, Albert Mohlke, Karen L. Boomsma, Dorret I. Caulfield, Mark J. Cupples, L. Adrienne Erdmann, Jeanette Fox, Caroline S. Gudnason, Vilmundur Gyllensten, Ulf Harris, Tamara B. Hayes, Richard B. Jarvelin, Marjo-Ritta Mooser, Vincent Munroe, Patricia B. Ouwehand, Willem H. Penninx, Brenda W. Pramstaller, Peter P. Quertermous, Thomas Rudan, Igor Samani, Nilesh J. Spector, Timothy D. Voelzke, Henry Watkins, Hugh Wilson, James F. Groop, Leif C. Haritunians, Talin Hu, Frank B. Kaplan, Robert C. Metspalu, Andres North, Kari E. Schlessinger, David Wareham, Nicholas J. Hunter, David J. O'Connell, Jeffrey R. Strachan, David P. Schadt, H. -Erich Thorsteinsdottir, Unnur Peltonen, Leena Uitterlinden, Andre G. Visscher, Peter M. Chatterjee, Nilanjan Loos, Ruth J. F. Boehnke, Michael McCarthy, Mark I. Ingelsson, Erik Lindgren, Cecilia M. Abecasis, Goncalo R. Stefansson, Kari Frayling, Timothy M. Hirschhorn, Joel N. CA Procardis Consortium TI Hundreds of variants clustered in genomic loci and biological pathways affect human height SO NATURE LA English DT Article ID WIDE ASSOCIATION ANALYSIS; COMMON VARIANTS; HERITABILITY; POPULATION; ADULT; STRATIFICATION; DISEASES; TRAITS; GROWTH; SNPS AB Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits(1), but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait(2,3). The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P<0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways. C1 [Allen, Hana Lango; Weedon, Michael N.; Wood, Andrew R.; Perry, John R. B.; Hattersley, Andrew T.; Frayling, Timothy M.] Univ Exeter, Peninsula Coll Med & Dent, Exeter EX1 2LU, Devon, England. [Estrada, Karol; Rivadeneira, Fernando; Aulchenko, Yurii S.; Amin, Najaf; vVan Meurs, Joyce B. 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[Petersmann, Astrid] Ernst Moritz Arndt Univ Greifswald, Inst Klin Chem, D-17475 Greifswald, Germany. [Petersmann, Astrid] Ernst Moritz Arndt Univ Greifswald, Lab Med, D-17475 Greifswald, Germany. [Pietilainen, Kirsi H.; Kaprio, Jaakko] Univ Helsinki, Dept Publ Hlth, Helsinki 00014, Finland. [Pietilainen, Kirsi H.; Rissanen, Aila] Univ Helsinki, Cent Hosp, Dept Psychiat, Obes Res unit, Helsinki, Finland. [Pouta, Anneli; Jarvelin, Marjo-Ritta] Natl Inst Hlth & Welf, Oulu 90101, Finland. [Riddertrale, Martin; Melander, Olle] Lund Univ, Dept Clin Sci, S-20502 Maimo, Sweden. [Sambrook, Jennifer G.; Ouwehand, Willem H.] Univ Cambridge, Dept Haematol, Cambridge CB2 OPT, England. [Sambrook, Jennifer G.; Ouwehand, Willem H.] Cambridge Ctr, Cambridge CB2 0PT, England. [Schmidt, Carsten Oliver; Hoffman, Wolfgang; Voelzke, Henry] Inst Community Med, D-17489 Greifswald, Germany. [Sinisalo, Juha; Nieminen, Markku S.] Univ Helsinki, Cent Hosp, Cardiovasc Lab, Div Cardiol, Helsinki 00029, Finland. [Smit, Jan H.; Penninx, Brenda W.] Vrije Univ Amsterdam, Med Ctr, Dept Psychiatry EMGO Inst, NL-1081 BT Amsterdam, Netherlands. [Zitting, Paavo] Lapland Cent Hosp, Dept Physiat, Rovaniemi 96101, Finland. [Farrall, Martin] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England. [McArdle, Wendy L.] Univ Bristol, Dept Social Med, ALSPAC, Bristol BS8 2BN, Avon, England. [Aben, Katja K.; Kiemeney, Lambertus] Comprehens Canc Ctr E, NL-6501 BG Nijmegen, Netherlands. [Beckmann, Jacques S.] CHU Vaudois, Univ Hosp, Serv Med Genet, CH-1011 Lausanne, Switzerland. [Beilby, John P.] Univ Western Australia, Sch Pathol & Lab Med, Nedlands, WA 6009, Australia. [Bergman, Richard N.] Univ So Calif, Keck Sch Med, Dept Phys & Biophys, Los Angeles, CA 90033 USA. [Collins, Francis S.] Natl Human Genome Res Inst, Natl Inst Hlth, Bethesda, MD 20892 USA. [den Heijer, Martin] Radboud Univ Nijmegen, Med Ctr, Dept Endocrinol, NL-6500 HB Nijmegen, Netherlands. [Hamsten, Anders] Karolinska Univ Hosp, Karolinska Inst, Dept Med, Atherosclerosis Res Unit, S-17176 Solna, Sweden. [Iribarren, Carlos] Kaiser Permanente No Calif, Div Res, Oakland, CA 94612 USA. [Iribarren, Carlos] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94107 USA. [Kahonen, Mika] Univ Tampere, Dept Clin Physiol, Tampere 33520, Finland. [Kahonen, Mika] Tampere Univ Hosp, Tampere 33520, Finland. [Kaprio, Jaakko] Natl Inst Hlth & Welf, Dept Mental Hlth & Substance Abuse Serv, Unit Child & Adolescent Mental Hlth, Helsinki 00271, Finland. [Kathiresan, Sekar; McCarthy, Mark I.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Kathiresan, Sekar; McCarthy, Mark I.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Kathiresan, Sekar; O'Donnell, Christopher J.] Boston Univ, Framingham, MA 01702 USA. [Kathiresan, Sekar; O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. [Kathiresan, Sekar] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Kiemeney, Lambertus] Radboud Univ Nijmegen, Med Ctr, Dept Epidemiol Biostatist & HTA, NL-6500 HB Nijmegen, Netherlands. [Kiemeney, Lambertus] Radboud Univ Nijmegen, Med Ctr, Dept Urol, NL-6500 HB Nijmegen, Netherlands. [Kocher, Thomas] Zentrum Zahn Mund & Kieferheilkunde, D-17489 Greifswald, Germany. [Launer, Lenore J.; Harris, Tamara B.] Natl Inst Hlth, NIA, Lab Epidemiol Demog, Bethesda, MD 20892 USA. [Lehtimaki, Terho] Univ Tampere, Dept Clin Chem, Tampere 33520, Finland. [Lehtimaki, Terho] Tampere Univ Hosp, Dept Clin Chem, Tampere 33520, Finland. [Mosley, Tom H., Jr.] Univ Mississippi, Div Geriatr, Med Ctr, Dept Med, Jackson, MS 39216 USA. [Musk, Arthur W.] Univ Western Australia, Sch Med & Pharmacol, Perth, WA 6009, Australia. [O'Donnell, Christopher J.] Natl Inst Hlth, Nat Lung & Blood Inst, Framingham, MA 01702 USA. [Oostra, Ben] Erasmus MC, Dept Clin Genet, NL-3015 GE Rotterdam, Netherlands. [Raitakari, Olli] Turku Univ, Res Ctr Appl & Prevent Cardiovasc Med, Turku 20520, Finland. [Raitakari, Olli] Turku Univ Hosp, Dept Clin Physiol, Turku 20520, Finland. [Schunkert, Heribert; Erdmann, Jeanette] Univ Lubeck, Med Klin 2, D-23562 Lubeck, Germany. [Shuldiner, Alan R.] Baltimore Vet Adm Med Ctr, Geriatr Res & Educ Clin Ctr, Baltimore, MD 21201 USA. [Siscovick, David S.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98101 USA. [Siscovick, David S.] Univ Washington, Dept Med, Seattle, WA 98195 USA. [Siscovick, David S.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. [Stumvoll, Michael; Toenjes, Anke] Univ Leipzig, Dept Med, D-04103 Leipzig, Germany. [Stumvoll, Michael] Univ Leipzig, LIFE Study Ctr, Leipzig, Germany. [Toenjes, Anke] Univ Leipzig, Coordinat Ctr Clin Trials, D-04103 Leipzig, Germany. [Tuomilehto, Jaakko] Natl Inst Hlth & Welf, Diabet Prevent Unit, Helsinki 00271, Finland. [Tuomilehto, Jaakko] Univ Helsinki, Dept Publ Hlth, Hjelt Inst, Helsinki 00014, Finland. [Tuomilehto, Jaakko] S Ostrobothnia Cent Hosp, Seinajoki 60220, Finland. [van Ommen, Gert-Jan] Leiden Univ, Med Ctr, Dept Human Genet, NL-2333 ZC Leiden, Netherlands. [van Ommen, Gert-Jan] Leiden Univ, Med Ctr, Ctr Med Syst Biol, NL-2333 ZC Leiden, Netherlands. [Viikari, Jorma] Univ Turku, Dept Med, Turku 20520, Finland. [Viikari, Jorma] Turku Univ Hosp, Turku 20520, Finland. [Heath, Andrew C.] Washington Univ, Sch Med, Dept Psychiat & Midwest, Res Inst Alcoholism, St Louis, MO 63108 USA. [Martin, Nicholas G.] Queensland Inst Med Res, Brisbane, Qld 4006, Australia. [Montgomery, Grant W.] Queensland Inst Med Res, Brisbane, Qld 4006, Australia. [Province, Michael A.] Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA. [Kayser, Manfred] Erasmus MC, Dept Forens Mol Biol, NL-3015 GE Rotterdam, Netherlands. [Arnold, Alice M.] Collaborat Hlth Studies Coordinating Ctr, Seattle, WA 98115 USA. [Boerwinkle, Eric] Univ Texas Houston, Hlth Sci Ctr, Ctr Human Genet, Houston, TX 77030 USA. [Boerwinkle, Eric] Univ Texas Houston, Hlth Sci Ctr, Inst Mol Med, Houston, TX 77030 USA. [Boerwinkle, Eric] Univ Texas Houston, Hlth Sci Ctr, Div Epidemiol, Houston, TX 77030 USA. [Hengstenberg, Christian] Univ Regensburg, Klin & Poliklin Innere Med 2, D-93053 Regensburg, Germany. [Hengstenberg, Christian] Univ Regensburg, Med Ctr, Innere Med 2, D-93053 Regensburg, Germany. [Lathrop, G. Mark] Ctr Natl Genotypage, F-91057 Paris, France. [Schreiber, Stefan] Univ Kiel, Univ Hosp Schleswig Holstein, Clin Mol Biol, D-24105 Kiel, Germany. [Schreiber, Stefan] Dept Internal Med 1, D-24105 Kiel, Germany. [Waterworth, Dawn; Mooser, Vincent] GlaxoSmithKline, Div Genet, King Of Prussia, PA 19406 USA. [Barroso, Ines] Addenbrookes Hosp, Metab Res Labs, Inst Metab Sci, Cambridge CB2 OQQ, England. [Fox, Caroline S.] NHLBI, Div Intramural Res, Framingham, MA 01702 USA. [Hayes, Richard B.] NYU, Med Ctr, New York, NY 10016 USA. [Jarvelin, Marjo-Ritta] Univ Oulu, Bioctr Oulu, Oulu 90014, Finland. [Penninx, Brenda W.] Leiden Univ, Med Ctr, Dept Psychiat, NL-2300 RC Leiden, Netherlands. [Penninx, Brenda W.] Univ Groningen, Univ Med Ctr Groningen, Dept Psychiat, NL-9713 GZ Groningen, Netherlands. [Pramstaller, Peter P.] Gen Cent Hosp, Dept Neurol, Bolzano, Italy. [Kaplan, Robert C.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10461 USA. [North, Kari E.] Univ N Carolina, Sch Publ Hlth, Carolina Ctr Genome Sci, Chapel Hill, NC 27514 USA. [Schlessinger, David] NIA, Genet Lab, Baltimore, MD 21224 USA. [Strachan, David P.] St Georges Univ London, Div Community Hlth Sci, London SW17 0RE, England. [Schadt, H. -Erich] Klinikum Grosshadern, D-81377 Munich, Germany. [Eriksson, Johan G.] Pacific Biosci, Menlo Pk, CA 94025 USA. Sage Bionetworks, Seattle, WA 98109 USA. [Thorsteinsdottir, Unnur] Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland. [Peltonen, Leena] Univ Helsinki, Dept Med Genet, Helsinki 00014, Finland. [McCarthy, Mark I.] Churchill Hosp, NIHR Oxford Biomed Res Ctr, Oxford OX3 7LJ, England. [Hirschhorn, Joel N.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. RP Allen, HL (reprint author), Univ Exeter, Peninsula Coll Med & Dent, Exeter EX1 2LU, Devon, England. RI Abecasis, Goncalo/B-7840-2010; Polasek, Ozren/B-6002-2011; Schreiber, Stefan/B-6748-2008; Beckmann, Jacques S /A-9772-2008; Voight, Benjamin/F-1775-2011; Aspelund, Thor/F-4826-2011; Segre, Ayellet/E-9800-2010; Aspelund, Thor/C-5983-2008; Kaplan, Robert/A-2526-2011; Spector, Tim/F-6533-2012; Ridderstrale, Martin/F-7678-2012; Kilpelainen, Tuomas/F-8569-2012; Rudan, Igor/I-1467-2012; Erdmann, Jeanette/P-7513-2014; Coin, Lachlan/A-9001-2014; Konig, Inke/A-4544-2009; Erdmann, Jeanette/A-4417-2009; Kolcic, Ivana/E-2713-2017; Feitosa, Mary/K-8044-2012; Hicks, Andrew/E-9518-2017; Gudnason, Vilmundur/K-6885-2015; Ripatti, Samuli/H-9446-2014; Wilson, James F/A-5704-2009; Montgomery, Grant/B-7148-2008; Meitinger, Thomas/O-1318-2015; Rivadeneira, Fernando/O-5385-2015; Prokopenko, Inga/H-3241-2014; Ziegler, Andreas/G-4246-2012; Aben, Katja/G-9686-2016; Yang, Jian/A-5852-2010; Smith, Albert/K-5150-2015; mangino, massimo/F-5134-2011; Hayward, Caroline/M-8818-2016; Deloukas, Panos/B-2922-2013; Nyholt, Dale/C-8384-2013; Marusic, Ana/E-7683-2013; Colaus, PsyColaus/K-6607-2013; Aulchenko, Yurii/M-8270-2013; Kiemeney, Lambertus/D-3357-2009; Pramstaller, Peter/C-2357-2008; Cooper, Matthew/J-4420-2014; Johansson, Asa/G-5270-2011; Palmer, Lyle/K-3196-2014; Salvi, Erika/C-1033-2015; Rioux, John/A-9599-2015 OI Polasek, Ozren/0000-0002-5765-1862; Schreiber, Stefan/0000-0003-2254-7771; Beckmann, Jacques S /0000-0002-9741-1900; Aspelund, Thor/0000-0002-7998-5433; Rudan, Igor/0000-0001-6993-6884; Visscher, Peter/0000-0002-2143-8760; Eriksson, Johan/0000-0002-2516-2060; Ouwehand, Willem/0000-0002-7744-1790; Kaprio, Jaakko/0000-0002-3716-2455; Rivolta, Carlo/0000-0002-0733-9950; Bergmann, Sven/0000-0002-6785-9034; Sinisalo, Juha/0000-0002-0169-5137; de Geus, Eco/0000-0001-6022-2666; Martin, Nicholas/0000-0003-4069-8020; Hayes, Richard/0000-0002-0918-661X; Jarvelin, Marjo-Riitta/0000-0002-2149-0630; Vandenput, Liesbeth/0000-0002-1712-6131; Watkins, Hugh/0000-0002-5287-9016; Abecasis, Goncalo/0000-0003-1509-1825; Peters, Marjolein/0000-0003-3167-9063; Erdmann, Jeanette/0000-0002-4486-6231; Gieger, Christian/0000-0001-6986-9554; Soranzo, Nicole/0000-0003-1095-3852; Zgaga, Lina/0000-0003-4089-9703; Esko, Tonu/0000-0003-1982-6569; Willer, Cristen/0000-0001-5645-4966; ELOSUA, ROBERTO/0000-0001-8235-0095; Goddard, Michael/0000-0001-9917-7946; sanna, serena/0000-0002-3768-1749; Gudbjartsson, Daniel/0000-0002-5222-9857; Johnson, Toby/0000-0002-5998-3270; Coin, Lachlan/0000-0002-4300-455X; Kolcic, Ivana/0000-0001-7918-6052; Feitosa, Mary/0000-0002-0933-2410; Hicks, Andrew/0000-0001-6320-0411; Pichler, Irene/0000-0001-8251-0757; Heard-Costa, Nancy/0000-0001-9730-0306; Cupples, L. Adrienne/0000-0003-0273-7965; Mulas, Antonella/0000-0002-6856-1483; Lango Allen, Hana/0000-0002-7803-8688; Magi, Reedik/0000-0002-2964-6011; Gudnason, Vilmundur/0000-0001-5696-0084; Ripatti, Samuli/0000-0002-0504-1202; Wilson, James F/0000-0001-5751-9178; Montgomery, Grant/0000-0002-4140-8139; Rivadeneira, Fernando/0000-0001-9435-9441; Prokopenko, Inga/0000-0003-1624-7457; Ziegler, Andreas/0000-0002-8386-5397; Aben, Katja/0000-0002-0214-2147; Yang, Jian/0000-0003-2001-2474; Smith, Albert/0000-0003-1942-5845; mangino, massimo/0000-0002-2167-7470; Hayward, Caroline/0000-0002-9405-9550; Deloukas, Panos/0000-0001-9251-070X; Marusic, Ana/0000-0001-6272-0917; Aulchenko, Yurii/0000-0002-7899-1575; Kiemeney, Lambertus/0000-0002-2368-1326; Cooper, Matthew/0000-0003-1139-3682; Johansson, Asa/0000-0002-2915-4498; Palmer, Lyle/0000-0002-1628-3055; Salvi, Erika/0000-0002-2724-2291; Rioux, John/0000-0001-7560-8326 FU Academy of Finland [104781, 117797, 120315, 121584, 126925, 129269, 129494, 129680, 213506]; Affymetrix for genotyping services [N02-HL-6-4278]; Agency for Science, Technology and Research of Singapore; ALF/LUA Gothenburg; Althingi (the Icelandic Parliament); Amgen; AstraZeneca AB; Australian National Health and Medical Research Council [241944, 389875, 389891, 389892, 389938, 442915, 442981, 496739, 496688, 552485, 613672]; Australian Research Council [DP0770096]; Biocentrum Helsinki; Boston Obesity Nutrition Research Center [DK46200]; British Diabetes Association; British Heart Foundation [PG/02/128]; British Heart Foundation Centre for Research Excellence, Oxford; CamStrad; Cancer Research UK; Centre for Neurogenomics and Cognitive Research; Chief Scientist Office of the Scottish Government [CZB/4/279]; Council of Health of the Academy of Finland; German Network of Diabetes; Diabetes UK; Donald W. Reynolds Foundation; Emil and Vera Cornell Foundation; Erasmus MC; Estonian Government [SF0180142s08]; European Commission [201413, ECOGENE:205419, BBMRI:212111, OPENGENE:245536, ENGAGE:HEALTH-F4-2007-201413, EURODIA:LSHG-CT-2004-518153, EU/WLRT-2001-01254, HEALTH-F2-2008-ENGAGE, HEALTH-F4-2007-201550, LSH-2006-037593, LSHG-CT-2006-018947, LSHG-CT-2006-01947, Procardis:LSHM-CT-2007-037273, POLYGENE:LSHC-CT-2005, QLG1-CT-2000-01643, QLG2-CT-2002-01254]; Eve Appeal; Finnish Ministry of Education; Finnish Diabetes Research Foundation; Finnish Diabetes Research Society; Finnish Foundation for Cardiovascular Research; Finnish Medical Society; Finska Lakaresallskapet; Folkhalsan Research Foundation; Fondation LeDucq; Foundation for Life and Health in Finland; Foundation for Strategic Research; GEN-AU; Genetic Association Information Network; German Bundesministerium fuer Forschung und Technology [01 AK 803 A-H, 01 IG 07015 G]; German Federal Ministry of Education and Research [01GS0831]; German Ministry for Health, Welfare and Sports; German Ministry of Cultural Affairs; German Ministry of Education, Culture and Science; German National Genome Research Net [01GS0823, 01ZZ0103, 01ZZ0403, 01ZZ9603, 03ZIK012]; German Research Council [KFO-152]; GlaxoSmithKline; Goteborg Medical Society; Gyllenberg Foundation; Helmholtz Center Munich; Juvenile Diabetes Research Foundation International [U01 DK062418]; Karolinska Institute; Knut and Alice Wallenberg Foundation; Lundberg Foundation; March of Dimes [6-FY-09-507]; MC Health; Medical Research Council UK [G0000649, G0000934, G0500539, G0600331, G0601261, G9521010D]; Microarray Core Facility of the Interdisciplinary Centre for Clinical Research [B27]; Mid-Atlantic Nutrition and Obesity Research Center of Maryland [P30 DK072488]; Ministry of Health and Department of Educational Assistance (South Tyrol, Italy); Ministry of Science, Education and Sport of the Republic of Croatia [216-1080315-0302]; Montreal Heart Institute Foundation; Narpes Health Care Foundation; National Cancer Institute; National Institute for Health Research Cambridge Biomedical Research Centre; National Institute for Health Research Oxford Biomedical Research Centre; National Institute for Health Research Comprehensive Biomedical Research Centre; National Institutes of Health [263-MA-410953, AA014041, AA07535, AA10248, AA13320, AA13321, AA13326, CA047988, CA49449, CA50385, CA65725, CA67262, CA87969, DA12854, DK062370, DK063491, DK072193, DK079466, DK080145, DK58845, HG002651, HG005214, HG005581, HL043851, HL084729, HL69757, HL71981, K08-AR055688]; ADA; Netherlands Genomics Initiative/Netherlands Consortium for Healthy Aging [050-060-810]; Netherlands Organisation for Scientific Research [175.010.2005.011, 911-03-012]; Netherlands Organization for the Health Research and Development [10-000-1002]; Netherlands Scientific Organization [904-61-090, 904-61-193, 480-04-004, 400-05-717, SPI 56-464-1419]; NIA; Nordic Center of Excellence in Disease Genetics; Novo Nordisk Foundation; Ollqvist Foundation; Paavo Nurmi Foundation; Perklen Foundation; Petrus and Augusta Hedlunds Foundation; Queensland Institute of Medical Research; Radboud University Nijmegen Medical Centre; Research Institute for Diseases in the Elderly [014-93-015]; Royal Swedish Academy of Science; Sahlgrenska Center for Cardiovascular and Metabolic Research [A305:188]; Siemens Healthcare, Erlangen, Germany; Signe and Ane Gyllenberg Foundation; Sigrid Juselius Foundation; Social Insurance Institution of Finland; Social Ministry of the Federal State of Mecklenburg-West Pomerania; South Tyrolean Sparkasse Foundation; Stockholm County Council; Support for Science Funding programme; Susan G. Komen Breast Cancer Foundation; Swedish Cancer Society; Swedish Cultural Foundation in Finland; Swedish Foundation for Strategic Research; Swedish Heart-Lung Foundation; Swedish Medical Research Council; Swedish National Cancer Institute; Swedish Research Council; Swedish Society of Medicine; Swiss National Science Foundation; Torsten and Ragnar Soderberg's Foundation; Vandervell Foundation; Vastra Gotaland Foundation; Wellcome Trust [072960, 075491, 079557, 079895, 083270, 068545/Z/02, 076113/B/04/Z, 076113/C/04/Z, 077016/Z/05/Z, 081682/Z/06/Z, 084183/Z/07/Z, 085301/Z/08/Z, 086596/Z/08/Z, 091746/Z/10/Z]; Wellcome Trust; Western Australian Genetic Epidemiology Resource; Western Australian DNA Bank; [560183]; [K2007-66X-20270-01-3]; [8691]; [33CSCO-122661] FX Several participating studies are members of the CHARGE and ENGAGE consortia. We acknowledge funding from the following organizations: the Academy of Finland (104781, 117797, 120315, 121584, 126925, 129269, 129494, 129680, 213506); Affymetrix for genotyping services (N02-HL-6-4278); Agency for Science, Technology and Research of Singapore; ALF/LUA Gothenburg; Althingi (the Icelandic Parliament); Amgen; AstraZeneca AB; Australian National Health and Medical Research Council (241944, 389875, 389891, 389892, 389938, 442915, 442981, 496739, 496688, 552485, 613672); Australian Research Council (DP0770096); Biocentrum Helsinki; Boston Obesity Nutrition Research Center (DK46200); British Diabetes Association; British Heart Foundation (PG/02/128); British Heart Foundation Centre for Research Excellence, Oxford; CamStrad; Cancer Research UK; Centre for Neurogenomics and Cognitive Research; Chief Scientist Office of the Scottish Government (CZB/4/279); Council of Health of the Academy of Finland; DIAB Core project of the German Network of Diabetes; Diabetes UK; Donald W.; Reynolds Foundation; Emil and Vera Cornell Foundation; Erasmus MC; Estonian Government (SF0180142s08); European Commission (201413, ECOGENE:205419, BBMRI:212111, OPENGENE:245536, ENGAGE:HEALTH-F4-2007-201413, EURODIA:LSHG-CT-2004-518153, EU/WLRT-2001-01254, HEALTH-F2-2008-ENGAGE, HEALTH-F4-2007-201550, LSH-2006-037593, LSHG-CT-2006-018947, LSHG-CT-2006-01947, Procardis:LSHM-CT-2007-037273, POLYGENE:LSHC-CT-2005, QLG1-CT-2000-01643, QLG2-CT-2002-01254, DG XII, Marie Curie Intra-European Fellowship); Eve Appeal; Finnish Ministry of Education; Finnish Diabetes Research Foundation; Finnish Diabetes Research Society; Finnish Foundation for Cardiovascular Research; Finnish Medical Society; Finska Lakaresallskapet; Folkhalsan Research Foundation; Fondation LeDucq; Foundation for Life and Health in Finland; Foundation for Strategic Research; GEN-AU-Programme 'GOLD'; Genetic Association Information Network; German Bundesministerium fuer Forschung und Technology (01 AK 803 A-H, 01 IG 07015 G); German Federal Ministry of Education and Research (01GS0831); German Ministry for Health, Welfare and Sports; German Ministry of Cultural Affairs; German Ministry of Education, Culture and Science; German National Genome Research Net (01GS0823, 01ZZ0103, 01ZZ0403, 01ZZ9603, 03ZIK012); German Research Council (KFO-152); GlaxoSmithKline; Goteborg Medical Society; Gyllenberg Foundation; Helmholtz Center Munich; Juvenile Diabetes Research Foundation International (U01 DK062418); Karolinska Institute; Knut and Alice Wallenberg Foundation; Lundberg Foundation; March of Dimes (6-FY-09-507); MC Health; Medical Research Council UK (G0000649, G0000934, G0500539, G0600331, G0601261, G9521010D, PrevMetSyn); Microarray Core Facility of the Interdisciplinary Centre for Clinical Research (B27); Mid-Atlantic Nutrition and Obesity Research Center of Maryland (P30 DK072488); Ministry of Health and Department of Educational Assistance (South Tyrol, Italy); Ministry of Science, Education and Sport of the Republic of Croatia (216-1080315-0302); Montreal Heart Institute Foundation; Narpes Health Care Foundation; National Cancer Institute; National Institute for Health Research Cambridge Biomedical Research Centre; National Institute for Health Research Oxford Biomedical Research Centre; National Institute for Health Research Comprehensive Biomedical Research Centre; National Institutes of Health (263-MA-410953, AA014041, AA07535, AA10248, AA13320, AA13321, AA13326, CA047988, CA49449, CA50385, CA65725, CA67262, CA87969, A12854, DK062370, DK063491, DK072193, DK079466, DK080145, DK58845, HG002651, HG005214, HG005581, HL043851, HL084729, HL69757, HL71981, K08-AR055688, K23-DK080145, K99-HL094535, M01-RR00425, MH084698, N01-AG12100, N01-AG12109, N01-HC15103, N01-HC25195, N01-HC35129, N01-HC45133, N01-HC55015, N01-HC55016, N01-HC55018N01-HC55022, N01-HC55222, N01-HC75150, N01-HC85079-N01-HC85086, N01-HG65403, R01-AG031890, R01 CA104021, R01-DK068336, R01-DK073490, R01-DK075681, R01-DK075787, R01-HL086694, R01-HL087641, R01-HL087647, R01-HL087652, R01-HL087676, R01-HL087679, R01-HL087700, R01-HL088119, R01-HL59367, R01-MH059160, R01-MH59565, R01-MH59566, R01-MH59571, R01-MH59586, R01-MH59587, R01-MH59588, R01-MH60870, R01-MH60879, R01-MH61675, R01-MH63706, R01-MH67257, R01-MH79469, R01-MH81800, RL1-MH083268, T32-HG00040, U01-CA098233, U01-GM074518, U01-HG004399, U01-HG004402, U01-HL080295, U01-HL084756, U01-HL72515, U01-MH79469, U01-MH79470, U54-RR020278, UL1-RR025005, Z01-AG00675, Z01-AG007380, Z01-HG000024; contract HHSN268200625226C; ADA Mentor-Based Postdoctoral Fellowship; Pew S; holarship for the Biomedical Sciences); Netherlands Genomics Initiative/Netherlands Consortium for Healthy Aging (050-060-810); Netherlands Organisation for Scientific Research (investment number 175.010.2005.011, 911-03-012); Netherlands Organization for the Health Research and Development (10-000-1002); Netherlands Scientific Organization (904-61-090, 904-61-193, 480-04-004, 400-05-717, Center for Medical Systems Biology (NOW Genomics), SPI 56-464-1419); NIA Intramural Research Program; Nordic Center of Excellence in Disease Genetics; Novo Nordisk Foundation; Ollqvist Foundation; Paavo Nurmi Foundation; Perklen Foundation; Petrus and Augusta Hedlunds Foundation; Queensland Institute of Medical Research; Radboud University Nijmegen Medical Centre; Research Institute for Diseases in the Elderly (014-93-015); Royal Swedish Academy of Science; Sahlgrenska Center for Cardiovascular and Metabolic Research (A305:188); Siemens Healthcare, Erlangen, Germany; Signe and Ane Gyllenberg Foundation; Sigrid Juselius Foundation; Social Insurance Institution of Finland; Social Ministry of the Federal State of Mecklenburg-West Pomerania; South Tyrolean Sparkasse Foundation; Stockholm County Council (560183); Support for Science Funding programme; Susan G. Komen Breast Cancer Foundation; Swedish Cancer Society; Swedish Cultural Foundation in Finland; Swedish Foundation for Strategic Research; Swedish Heart-Lung Foundation; Swedish Medical Research Council (K2007-66X-20270-01-3, 8691); Swedish National Cancer Institute; Swedish Research Council; Swedish Society of Medicine; Swiss National Science Foundation (33CSCO-122661); Torsten and Ragnar Soderberg's Foundation; Vandervell Foundation; Vastra Gotaland Foundation; Wellcome Trust (072960, 075491, 079557, 079895, 083270, 068545/Z/02, 076113/B/04/Z, 076113/C/04/Z, 076113/C/04/Z, 077016/Z/05/Z, 081682/Z/06/Z, 084183/Z/07/Z, 085301/Z/08/Z, 086596/Z/ 08/Z, 091746/Z/10/Z; Wellcome Trust Research Career Development Fellowship); Western Australian Genetic Epidemiology Resource and the Western Australian DNA Bank (both National Health and Medical Research Council of Australia Enabling Facilities). A detailed list of acknowledgements by study is given in the Supplementary Information. NR 28 TC 530 Z9 539 U1 12 U2 149 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD OCT 14 PY 2010 VL 467 IS 7317 BP 832 EP 838 DI 10.1038/nature09410 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 663PB UT WOS:000282898700065 ER PT J AU Weinberg, AN Branda, JA AF Weinberg, Arnold N. Branda, John A. TI A Woman with Fever after a Cat Bite Infection with Francisella tularensis (tularemia) SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article; Proceedings Paper CT Conference on Medical Case CY MAY 01, 2009 CL MA ID DIAGNOSIS; THERAPY C1 [Weinberg, Arnold N.] Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA. [Branda, John A.] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. [Weinberg, Arnold N.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. [Branda, John A.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Weinberg, AN (reprint author), Massachusetts Gen Hosp, Dept Med, Div Infect Dis, Boston, MA 02114 USA. NR 17 TC 6 Z9 6 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 OCT 14 PY 2010 VL 363 IS 16 BP 1560 EP 1568 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 663KP UT WOS:000282887100012 PM 20942673 ER PT J AU Birrer, MJ AF Birrer, Michael J. TI The Origin of Ovarian Cancer - Is It Getting Clearer? SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID ENDOMETRIOSIS; TRANSFORMATION; TUMORS C1 Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Birrer, MJ (reprint author), Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. NR 12 TC 16 Z9 16 U1 0 U2 4 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 14 PY 2010 VL 363 IS 16 BP 1574 EP 1575 DI 10.1056/NEJMe1009527 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 663KP UT WOS:000282887100015 PM 20942676 ER PT J AU Nakou, M Bertsias, G Stagakis, I Centola, M Tassiulas, I Hatziapostolou, M Kritikos, I Goulielmos, G Boumpas, DT Iliopoulos, D AF Nakou, Magdalene Bertsias, George Stagakis, Ilias Centola, Michael Tassiulas, Ioannis Hatziapostolou, Maria Kritikos, Iraklis Goulielmos, George Boumpas, Dimitrios T. Iliopoulos, Dimitrios TI Gene Network Analysis of Bone Marrow Mononuclear Cells Reveals Activation of Multiple Kinase Pathways in Human Systemic Lupus Erythematosus SO PLOS ONE LA English DT Article ID NF-KAPPA-B; GRANULOPOIESIS SIGNATURES; T-CELLS; EXPRESSION; INTERFERON; DISEASE; CANCER; BLOOD; ADENOCARCINOMA; INFLAMMATION AB Background: Gene profiling studies provide important information for key molecules relevant to a disease but are less informative of protein-protein interactions, post-translational modifications and regulation by targeted subcellular localization. Integration of genomic data and construction of functional gene networks may provide additional insights into complex diseases such as systemic lupus erythematosus (SLE). Methodology/Principal Findings: We analyzed gene expression microarray data of bone marrow mononuclear cells (BMMCs) from 20 SLE patients (11 with active disease) and 10 controls. Gene networks were constructed using the bioinformatic tool Ingenuity Gene Network Analysis. In SLE patients, comparative analysis of BMMCs genes revealed a network with 19 central nodes as major gene regulators including ERK, JNK, and p38 MAP kinases, insulin, Ca(2+) and STAT3. Comparison between active versus inactive SLE identified 30 central nodes associated with immune response, protein synthesis, and post-transcriptional modification. A high degree of identity between networks in active SLE and non-Hodgkin's lymphoma (NHL) patients was found, with overlapping central nodes including kinases (MAPK, ERK, JNK, PKC), transcription factors (NF-kappaB, STAT3), and insulin. In validation studies, western blot analysis in splenic B cells from 5-month-old NZB/NZW F1 lupus mice showed activation of STAT3, ITGB2, HSPB1, ERK, JNK, p38, and p32 kinases, and downregulation of FOXO3 and VDR compared to normal C57Bl/6 mice. Conclusions/Significance: Gene network analysis of lupus BMMCs identified central gene regulators implicated in disease pathogenesis which could represent targets of novel therapies in human SLE. The high similarity between active SLE and NHL networks provides a molecular basis for the reported association of the former with lymphoid malignancies. C1 [Nakou, Magdalene; Bertsias, George; Stagakis, Ilias; Tassiulas, Ioannis; Kritikos, Iraklis; Goulielmos, George; Boumpas, Dimitrios T.] Univ Crete, Div Rheumatol Clin Immunol & Allergy, Sch Med, Iraklion, Greece. [Bertsias, George; Stagakis, Ilias; Tassiulas, Ioannis; Boumpas, Dimitrios T.] Fdn Res & Technol, Inst Mol Biol & Biotechnol, Iraklion, Greece. [Centola, Michael] Oklahoma Med Res Fdn, Microarray Res Facil, Oklahoma City, OK 73104 USA. [Hatziapostolou, Maria; Iliopoulos, Dimitrios] Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [Hatziapostolou, Maria; Iliopoulos, Dimitrios] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Nakou, M (reprint author), Univ Crete, Div Rheumatol Clin Immunol & Allergy, Sch Med, Iraklion, Greece. EM dimitrios_iliopoulos@dfci.harvard.edu RI Hatziapostolou, Maria/N-1820-2015 OI Hatziapostolou, Maria/0000-0003-2493-7028 FU Hellenic Rheumatology Society FX This work has been supported by Hellenic Rheumatology Society grants. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 37 TC 10 Z9 11 U1 0 U2 0 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD OCT 14 PY 2010 VL 5 IS 10 AR e13351 DI 10.1371/journal.pone.0013351 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 664DX UT WOS:000282941000006 PM 20976278 ER PT J AU Sima, CS Panageas, KS Schrag, D AF Sima, Camelia S. Panageas, Katherine S. Schrag, Deborah TI Cancer Screening Among Patients With Advanced Cancer SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID UNITED-STATES; BREAST-CANCER; INCIDENCE TRENDS; PROSTATE-CANCER; MAMMOGRAPHY; OVERDIAGNOSIS; CARE; PHYSICIANS; WOMEN AB Context Cancer screening has been integrated into routine primary care but does not benefit patients with limited life expectancy. Objective To evaluate the extent to which patients with advanced cancer continue to be screened for new cancers. Design, Setting, and Participants Utilization of cancer screening procedures (mammography, Papanicolaou test, prostate-specific antigen [PSA], and lower gastrointestinal [GI] endoscopy) was assessed in 87 736 fee-for-service Medicare enrollees aged 65 years or older diagnosed with advanced lung, colorectal, pancreatic, gastroesophageal, or breast cancer between 1998 and 2005, and reported to one of the Surveillance, Epidemiology, and End Results (SEER) tumor registries. Participants were followed up until death or December 31, 2007, whichever came first. A group of 87 307 Medicare enrollees without cancer were individually matched by age, sex, race, and SEER registry to patients with cancer and observed over the same period to evaluate screening rates in context. Demographic and clinical characteristics associated with screening were also investigated. Main Outcome Measure For each cancer screening test, utilization rates were defined as the percentage of patients who were screened following the diagnosis of an incurable cancer. Results Among women following advanced cancer diagnosis compared with controls, at least 1 screening mammogram was received by 8.9% (95% confidence interval [CI], 8.6%-9.1%) vs 22.0% (95% CI, 21.7%-22.5%); Papanicolaou test screening was received by 5.8% (95% CI, 5.6%-6.1%) vs 12.5% (95% CI, 12.2%-12.8%). Among men following advanced cancer diagnosis compared with controls, PSA test was received by 15.0% (95% CI, 14.7%-15.3%) vs 27.2% (95% CI, 26.8%-27.6%). For all patients following advanced diagnosis compared with controls, lower GI endoscopy was received by 1.7% (95% CI, 1.6%-1.8%) vs 4.7% (95% CI, 4.6%-4.9%). Screening was more frequent among patients with a recent history of screening (16.2% [95% CI, 15.4%-16.9%] of these patients had mammography, 14.7% [95% CI, 13.7%-15.6%] had a Papanicolaou test, 23.3% [95% CI, 22.6%-24.0%] had a PSA test, and 6.1% [95% CI, 5.2%-7.0%] had lower GI endoscopy). Conclusion A sizeable proportion of patients with advanced cancer continue to undergo cancer screening tests that do not have a meaningful likelihood of providing benefit. JAMA. 2010;304(14):1584-1591 www.jama.com C1 [Sima, Camelia S.; Panageas, Katherine S.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10065 USA. [Schrag, Deborah] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Sima, CS (reprint author), Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, 307 E 63rd St,2nd Floor, New York, NY 10065 USA. EM simac@mskcc.org FU National Cancer Institute [R01 1147503]; Schrag FX Obtained funding: Schrag.; This research was supported by grant R01 1147503 from the National Cancer Institute (Dr Schrag). NR 35 TC 38 Z9 39 U1 0 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD OCT 13 PY 2010 VL 304 IS 14 BP 1584 EP 1591 DI 10.1001/jama.2010.1449 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 662OE UT WOS:000282816500023 PM 20940384 ER PT J AU Steinman, MA Hanlon, JT AF Steinman, Michael A. Hanlon, Joseph T. TI Managing Medications in Clinically Complex Elders "There's Got to Be a Happy Medium" SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID ADVERSE DRUG EVENTS; RANDOMIZED-CONTROLLED-TRIALS; EMERGENCY-DEPARTMENT VISITS; OLDER-ADULTS; PRIMARY-CARE; AMBULATORY-CARE; RISK-FACTORS; DISCONTINUING MEDICATIONS; PHARMACIST INTERVENTION; GENERAL-PRACTITIONERS AB Multiple medication use is common in older adults and may ameliorate symptoms, improve and extend quality of life, and occasionally cure disease. Unfortunately, multiple medication use is also a major risk factor for prescribing and adherence problems, adverse drug events, and other adverse health outcomes. Using the case of an older patient taking multiple medications, this article summarizes the evidence-based literature about improving medication use and withdrawing specific drugs and drug classes. It also describes a systematic approach for how health professionals can assess and improve medication regimens to benefit patients and their caregivers and families. JAMA. 2010;304(14):1592-1601 www.jama.com C1 [Steinman, Michael A.] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Steinman, Michael A.] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. [Hanlon, Joseph T.] Univ Pittsburgh, Dept Epidemiol, Dept Med, Div Geriatr Med, Pittsburgh, PA 15261 USA. [Hanlon, Joseph T.] Univ Pittsburgh, Dept Pharm & Therapeut, Pittsburgh, PA USA. [Hanlon, Joseph T.] Vet Affairs Pittsburgh Healthcare Syst, Geriatr Res Educ & Clin Ctr, Pittsburgh, PA USA. [Hanlon, Joseph T.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equity Res & Promot, Pittsburgh, PA USA. RP Steinman, MA (reprint author), San Francisco VA Med Ctr, 4150 Clement St,Box 181G, San Francisco, CA 94121 USA. EM mike.steinman@ucsf.edu FU National Institute on Aging and the American Federation for Aging Research [K23 AG030999]; Department of Veterans Affairs [IIR 06-080]; National Institute of Aging [R01AG027017, P30AG024827, T32 AG021885, K07AG033174, R01AG034056]; National Institute of Mental Health [R34 MH082682]; National Institute of Nursing Research [R01 NR010135]; Agency for Healthcare Research and Quality [HS017695, HS018721]; Veterans Administration Health Services [IIR06-062]; SCAN Foundation FX Dr Steinman was supported by the National Institute on Aging and the American Federation for Aging Research (K23 AG030999) and by the Department of Veterans Affairs (IIR 06-080). Dr Hanlon was supported by grants from the National Institute of Aging (R01AG027017, P30AG024827, T32 AG021885, K07AG033174, and R01AG034056), the National Institute of Mental Health (R34 MH082682), the National Institute of Nursing Research (R01 NR010135), the Agency for Healthcare Research and Quality (HS017695 and HS018721), and a Veterans Administration Health Services research grant (IIR06-062). The Care of the Aging Patient series is made possible by funding from The SCAN Foundation. NR 97 TC 133 Z9 136 U1 3 U2 10 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD OCT 13 PY 2010 VL 304 IS 14 BP 1592 EP 1601 DI 10.1001/jama.2010.1482 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 662OE UT WOS:000282816500024 PM 20940385 ER PT J AU Riess, H AF Riess, Helen TI Empathy in Medicine-A Neurobiological Perspective SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID PSYCHOTHERAPY C1 Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wang Ambulatory Care Ctr,Dept Psychiat, Boston, MA 02114 USA. RP Riess, H (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Wang Ambulatory Care Ctr,Dept Psychiat, 15 Parkman St,Ste 812, Boston, MA 02114 USA. EM hriess@partners.org NR 10 TC 29 Z9 29 U1 0 U2 8 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD OCT 13 PY 2010 VL 304 IS 14 BP 1604 EP 1605 DI 10.1001/jama.2010.1455 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 662OE UT WOS:000282816500026 PM 20940387 ER PT J AU Jones, SR Kerr, CE Wan, QA Pritchett, DL Hamalainen, M Moore, CI AF Jones, Stephanie R. Kerr, Catherine E. Wan, Qian Pritchett, Dominique L. Haemaelaeinen, Matti Moore, Christopher I. TI Cued Spatial Attention Drives Functionally Relevant Modulation of the Mu Rhythm in Primary Somatosensory Cortex SO JOURNAL OF NEUROSCIENCE LA English DT Article ID VISUOSPATIAL ATTENTION; ALPHA-RHYTHMS; OCCIPITAL CORTEX; EVOKED-RESPONSES; FOCAL ATTENTION; OSCILLATIONS; EEG; SUPPRESSION; PERFORMANCE; ACTIVATION AB Cued spatial attention modulates functionally relevant alpha rhythms in visual cortices in humans. Here, we present evidence for analogous phenomena in primary somatosensory neocortex (SI). Using magnetoencephalography, we measured changes in the SI mu rhythm containing mu-alpha (7-14 Hz) and mu-beta (15-29 Hz) components. We found that cued attention impacted mu-alpha in the somatopically localized hand representation in SI, showing decreased power after attention was cued to the hand and increased power after attention was cued to the foot, with significant differences observed 500 -1100 ms after cue. Mu-beta showed differences in a time window 800-850 ms after cue. The visual cue also drove an early evoked response beginning similar to 70 ms after cue with distinct peaks modulated with cued attention. Distinct components of the tactile stimulus-evoked response were also modulated with cued attention. Analysis of a second dataset showed that, on a trial-by-trial basis, tactile detection probabilities decreased linearly with prestimulus mu-alpha and mu-beta power. These results support the growing consensus that cue-induced alpha modulation is a functionally relevant sensory gating mechanism deployed by attention. Further, while cued attention had a weaker effect on the allocation of mu-beta, oscillations in this band also predicted tactile detection. C1 [Jones, Stephanie R.; Haemaelaeinen, Matti] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Kerr, Catherine E.; Wan, Qian] Harvard Univ, Sch Med, Harvard Osher Res Ctr, Boston, MA 02215 USA. [Wan, Qian; Pritchett, Dominique L.; Moore, Christopher I.] MIT, McGovern Inst Brain Res, Cambridge, MA 02139 USA. RP Jones, SR (reprint author), Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, 149 13th St,Suite 2301, Charlestown, MA 02129 USA. EM srjones@nmr.mgh.harvard.edu RI Hamalainen, Matti/C-8507-2013; OI Pritchett, Dominique/0000-0003-1187-1162 FU National Institutes of Health [P41RR14075, K25MH072941, K01AT003459, 1R01-NS045130-01, T32 GM007484]; National Science Foundation [0316933]; Osher Institute; Athinoula A. Martinos Center for Biomedical Imaging; McGovern Institute for Brain Research FX This work was supported by the National Institutes of Health (P41RR14075, K25MH072941, K01AT003459, 1R01-NS045130-01, and T32 GM007484), the National Science Foundation (0316933), and the Osher Institute. We thank the anonymous reviewers for particularly thoughtful comments on earlier drafts of this manuscript and the Athinoula A. Martinos Center for Biomedical Imaging and the McGovern Institute for Brain Research for their support of this research. NR 38 TC 108 Z9 108 U1 0 U2 19 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD OCT 13 PY 2010 VL 30 IS 41 BP 13760 EP 13765 DI 10.1523/JNEUROSCI.2969-10.2010 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 663HS UT WOS:000282874600022 PM 20943916 ER PT J AU Krienen, FM Tu, PC Buckner, RL AF Krienen, Fenna M. Tu, Pei-Chi Buckner, Randy L. TI Clan Mentality: Evidence That the Medial Prefrontal Cortex Responds to Close Others SO JOURNAL OF NEUROSCIENCE LA English DT Article ID EVENT-RELATED FMRI; ANTERIOR CINGULATE CORTEX; SOCIAL COGNITION; DECISION-MAKING; MACAQUE MONKEY; FRONTAL-CORTEX; NEURAL BASIS; SELF; EMOTION; KNOWLEDGE AB Kinship, friendship alliances, and perceptions of others' beliefs guide social interactions and are central to cohesive group behavior. Under certain conditions, brain systems that involve regions along the frontal midline increase activity when inferences are drawn about others who share a similar view to one's own (similarity). A prominent hypothesis is that these regions contribute to social cognition by simulating the other person's perspective based on one's own experience. An alternative is that certain regions process the social relevance of the person (closeness) to oneself and contribute to the assessment akin to signals that govern behavioral approach responses. These alternatives were explored across four functional magnetic resonance imaging experiments (n = 98). Experiment 1 localized the target midline regions in the rostral anterior cingulate cortex and anterior medial prefrontal cortex by having participants make personal judgments. The two dimensions (similarity, closeness) were crossed in experiment 2 using actual friends of the participant and unknown others. Making judgments about oneself and friends resulted in increased midline response relative to unknown others regardless of whether the friends shared similar views as the participant. Experiment 3 revealed that similarity was not a factor even when close others were not included. Experiment 4 directly contrasted two extremes: participants made inferences about similar, unknown others and dissimilar friends. Judgments about the close others again increased blood oxygenation level-dependent response along the frontal midline. These results encourage further exploration of the idea that frontal systems linked with limbic circuits facilitate assessment of the relevance or personal significance in social contexts. C1 [Krienen, Fenna M.; Buckner, Randy L.] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. [Krienen, Fenna M.; Buckner, Randy L.] Harvard Univ, Ctr Brain Sci, Cambridge, MA 02138 USA. [Krienen, Fenna M.; Buckner, Randy L.] Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA. [Krienen, Fenna M.; Buckner, Randy L.] Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Tu, Pei-Chi; Buckner, Randy L.] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA 02129 USA. [Tu, Pei-Chi; Buckner, Randy L.] Massachusetts Gen Hosp, Dept Radiol, Charlestown, MA 02129 USA. [Tu, Pei-Chi] Natl Yang Ming Univ, Sch Life Sci, Inst Neurosci, Taipei 112, Taiwan. RP Krienen, FM (reprint author), Harvard Univ, Ctr Brain Sci 280 04, 52 Oxford St, Cambridge, MA 02138 USA. EM krienen@wjh.harvard.edu FU National Institute on Aging [AG-021910, AG-034556]; Howard Hughes Medical Institute; Simons Foundation; Department of Defense; Ashford Graduate Fellowship; Harvard Center for Brain Science Neuro-imaging Core; Athinoula A. Martinos Center for Biomedical Imaging FX This work was supported by the National Institute on Aging (Grants AG-021910 and AG-034556), the Howard Hughes Medical Institute, the Simons Foundation, fellowships from the Department of Defense, and an Ashford Graduate Fellowship in the Sciences (F. M. K.). We thank Jason Mitchell, Jessica Andrews-Hanna, Amitai Shenhav, and Aaron Bornstein for insightful comments and discussion; Dost Ongur and Joel Price for discussion of anatomy; Rebecca Saxe for pointers to relevant literature; and Angela Castellanos, Katherine Powers, and Tammy Moran for assistance with data collection. MRI imaging support was provided by the Harvard Center for Brain Science Neuro-imaging Core and the Athinoula A. Martinos Center for Biomedical Imaging. NR 75 TC 82 Z9 85 U1 1 U2 14 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD OCT 13 PY 2010 VL 30 IS 41 BP 13906 EP 13915 DI 10.1523/JNEUROSCI.2180-10.2010 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 663HS UT WOS:000282874600037 PM 20943931 ER PT J AU Shabani, S Foster, R Gubner, N Phillips, TJ Mark, GP AF Shabani, S. Foster, R. Gubner, N. Phillips, T. J. Mark, G. P. TI MUSCARINIC TYPE 2 RECEPTORS IN THE LATERAL DORSAL TEGMENTAL AREA MODULATE COCAINE AND FOOD SEEKING BEHAVIOR IN RATS SO NEUROSCIENCE LA English DT Article DE cocaine; addiction; acetylcholine; muscarinic; self-administration; motivation ID ACCUMBAL DOPAMINE RELEASE; NUCLEUS-ACCUMBENS; CHOLINERGIC NEURONS; ACETYLCHOLINE-RECEPTORS; GLUTAMATE RECEPTORS; RETICULAR-FORMATION; GABAERGIC NEURONS; IN-VITRO; STIMULATION; LATERODORSAL AB The cholinergic input from the lateral dorsal tegmental area (LDTg) modulates the dopamine cells of the ventral tegmental area (VTA) and plays an important role in cocaine taking. Specific pharmacological agents that block or stimulate muscarinic receptors in the LDTg change acetylcholine (ACh) levels in the VTA. Furthermore, manipulations of cholinergic input in the VTA can change cocaine taking. In the current study, the ACh output from the LDTg was attenuated by treatment with the selective muscarinic type 2 (M2) autoreceptor agonist oxotremorine . sesquifumarate (OxoSQ). We hypothesized that OxoSQ would reduce the motivation of rats to self-administer both natural and drug rewards. Animals were tested on progressive ratio (PR) schedules of reinforcement for food pellets and cocaine. On test days, animals on food and on cocaine schedules were bilaterally microinjected prior to the test. Rats received either LDTg OxoSQ infusions or LDTg artificial cerebrospinal fluid (aCSF) infusions in a within-subjects design. In addition, infusions were delivered into a dorsal brain area above the LDTg as an anatomical control region. OxoSQ microinjection in the LDTg, compared to aCSF, significantly reduced both the number of self-administered pellets and cocaine infusions during the initial half of the session; this reduction was dose-dependent. OxoSQ microinjections into the area just dorsal to the LDTg had no significant effect on self-administration of food pellets or cocaine. Animals were also tested in locomotor activity chambers for motor effects following the above microinjections. Locomotor activity was mildly increased by OxoSQ microinjection into the LDTg during the initial half of the session. Overall, these data suggest that LDTg cholinergic neurons play an important role in modifying the reinforcing value of natural and drug rewards. These effects cannot be attributed to significant alterations of locomotor behavior and are likely accomplished through LDTg muscarinic autoreceptors. Published by Elsevier Ltd on behalf of IBRO. C1 [Shabani, S.; Foster, R.; Gubner, N.; Phillips, T. J.; Mark, G. P.] Oregon Hlth & Sci Univ, Portland, OR 97239 USA. [Phillips, T. J.] Portland VA Med Ctr, Portland, OR 97239 USA. RP Shabani, S (reprint author), Oregon Hlth & Sci Univ, 3181 SW Sam Jackson Pk,Rd L470, Portland, OR 97239 USA. EM shabanis@ohsu.edu FU NIH [RO1 DA14639, T32 DA07262, P50 DA018165]; Department of Veterans Affairs FX We would like to thank Dr. Stephen T. Hansen for providing training on all the surgical procedures mentioned in this study, Dr. Ted Benice for his help with Med Associates software, and Tamie Painter for her technical support. We would also like to thank Dr. Suzanne Mitchell for her advice and generous support with lab space and equipment during the locomotor activity experiment. This work was supported by NIH grants RO1 DA14639 and T32 DA07262, and P50 DA018165, and by the Department of Veterans Affairs. NR 59 TC 8 Z9 10 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 EI 1873-7544 J9 NEUROSCIENCE JI Neuroscience PD OCT 13 PY 2010 VL 170 IS 2 BP 559 EP 569 DI 10.1016/j.neuroscience.2010.07.028 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 651PH UT WOS:000281939100018 PM 20667466 ER PT J AU Kao, PF Davis, DA Banigan, MG Vanderburg, CR Seshadri, S Delalle, I AF Kao, Patricia F. Davis, David A. Banigan, Meredith G. Vanderburg, Charles R. Seshadri, Sudha Delalle, Ivana TI Modulators of Cytoskeletal Reorganization in CA1 Hippocampal Neurons Show Increased Expression in Patients at Mid-Stage Alzheimer's Disease SO PLOS ONE LA English DT Article ID BDNF MESSENGER-RNA; LONG-TERM-MEMORY; NEUROTROPHIC FACTOR; GROWTH CONES; HUMAN BRAIN; IN-VITRO; F-ACTIN; PROTEIN; TRKB; RAT AB During the progression of Alzheimer's disease (AD), hippocampal neurons undergo cytoskeletal reorganization, resulting in degenerative as well as regenerative changes. As neurofibrillary tangles form and dystrophic neurites appear, sprouting neuronal processes with growth cones emerge. Actin and tubulin are indispensable for normal neurite development and regenerative responses to injury and neurodegenerative stimuli. We have previously shown that actin capping protein beta2 subunit, Capzb2, binds tubulin and, in the presence of tau, affects microtubule polymerization necessary for neurite outgrowth and normal growth cone morphology. Accordingly, Capzb2 silencing in hippocampal neurons resulted in short, dystrophic neurites, seen in neurodegenerative diseases including AD. Here we demonstrate the statistically significant increase in the Capzb2 expression in the postmortem hippocampi in persons at mid-stage, Braak and Braak stage (BB) III-IV, non-familial AD in comparison to controls. The dynamics of Capzb2 expression in progressive AD stages cannot be attributed to reactive astrocytosis. Moreover, the increased expression of Capzb2 mRNA in CA1 pyramidal neurons in AD BB III-IV is accompanied by an increased mRNA expression of brain derived neurotrophic factor (BDNF) receptor tyrosine kinase B (TrkB), mediator of synaptic plasticity in hippocampal neurons. Thus, the up-regulation of Capzb2 and TrkB may reflect cytoskeletal reorganization and/or regenerative response occurring in hippocampal CA1 neurons at a specific stage of AD progression. C1 [Kao, Patricia F.; Davis, David A.; Delalle, Ivana] Boston Univ, Sch Med, Dept Pathol & Lab Med, Boston, MA 02118 USA. [Banigan, Meredith G.; Vanderburg, Charles R.] Massachusetts Gen Hosp, Harvard NeuroDiscovery Ctr, Adv Tissue Res Ctr, Charlestown, MA USA. [Seshadri, Sudha] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. RP Kao, PF (reprint author), Boston Univ, Sch Med, Dept Pathol & Lab Med, Boston, MA 02118 USA. EM idelalle@bu.edu OI Seshadri, Sudha/0000-0001-6135-2622 FU National Institutes of Health [T32 AG00015-21] FX Patricia Kao and David Davis were supported by the National Institutes of Health grant T32 AG00015-21. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 48 TC 14 Z9 14 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD OCT 13 PY 2010 VL 5 IS 10 AR e13337 DI 10.1371/journal.pone.0013337 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 663FZ UT WOS:000282869800032 PM 20967212 ER PT J AU Zhukovsky, MA Basmaciogullari, S Pacheco, B Wang, LP Madani, N Haim, H Sodroski, J AF Zhukovsky, Mikhail A. Basmaciogullari, Stephane Pacheco, Beatriz Wang, Liping Madani, Navid Haim, Hillel Sodroski, Joseph TI Thermal Stability of the Human Immunodeficiency Virus Type 1 (HIV-1) Receptors, CD4 and CXCR4, Reconstituted in Proteoliposomes SO PLOS ONE LA English DT Article ID GLYCOPROTEIN-MEDIATED FUSION; CELL-DERIVED FACTOR-1-ALPHA; PROTEIN-COUPLED RECEPTORS; CHEMOKINE RECEPTOR; MEMBRANE-VESICLES; CRYSTAL-STRUCTURE; SMALL-MOLECULE; PARAMAGNETIC PROTEOLIPOSOMES; FUNCTIONAL-ANALYSIS; IMMUNOGLOBULIN-G AB Background: The entry of human immunodeficiency virus (HIV-1) into host cells involves the interaction of the viral exterior envelope glycoprotein, gp120, and receptors on the target cell. The HIV-1 receptors are CD4 and one of two chemokine receptors, CCR5 or CXCR4. Methodology/Principal Findings: We created proteoliposomes that contain CD4, the primary HIV-1 receptor, and one of the coreceptors, CXCR4. Antibodies against CD4 and CXCR4 specifically bound the proteoliposomes. CXCL12, the natural ligand for CXCR4, and the small-molecule CXCR4 antagonist, AMD3100, bound the proteoliposomes with affinities close to those associated with the binding of these molecules to cells expressing CXCR4 and CD4. The HIV-1 gp120 exterior envelope glycoprotein bound tightly to proteoliposomes expressing only CD4 and, in the presence of soluble CD4, bound weakly to proteoliposomes expressing only CXCR4. The thermal stability of CD4 and CXCR4 inserted into liposomes was examined. Thermal denaturation of CXCR4 followed second-order kinetics, with an activation energy (E-a) of 269 kJ/mol (64.3 kcal/mol) and an inactivation temperature (T-i) of 56 degrees C. Thermal inactivation of CD4 exhibited a reaction order of 1.3, an E-a of 278 kJ/mol (66.5 kcal/mol), and a T-i of 52.2 degrees C. The second-order denaturation kinetics of CXCR4 is unusual among G protein-coupled receptors, and may result from dimeric interactions between CXCR4 molecules. Conclusions/Significance: Our studies with proteoliposomes containing the native HIV-1 receptors allowed an examination of the binding of biologically important ligands and revealed the higher-order denaturation kinetics of these receptors. CD4/CXCR4-proteoliposomes may be useful for the study of virus-target cell interactions and for the identification of inhibitors. C1 [Zhukovsky, Mikhail A.; Basmaciogullari, Stephane; Pacheco, Beatriz; Wang, Liping; Madani, Navid; Haim, Hillel; Sodroski, Joseph] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS,Dept Pathol,Div AIDS, Boston, MA 02115 USA. [Zhukovsky, Mikhail A.] Max Planck Inst Biophys Chem, Dept Struct Dynam Biochem Syst, D-37077 Gottingen, Germany. [Sodroski, Joseph] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA. RP Zhukovsky, MA (reprint author), Univ Saarland, Chair Biol Expt Phys, D-6600 Saarbrucken, Germany. EM joseph_sodroski@dfci.harvard.edu FU National Institutes of Health [AI24755, AI42848]; International AIDS Vaccine Initiative FX This work was supported by two grants (AI24755 and AI42848) from the National Institutes of Health (http://www.nih.gov), by a gift from the late William F. McCarty-Cooper, and by funds from the International AIDS Vaccine Initiative (http://www.iavi.org). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 126 TC 4 Z9 4 U1 0 U2 1 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 OCT 13 PY 2010 VL 5 IS 10 AR e13249 DI 10.1371/journal.pone.0013249 PG 17 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 663FZ UT WOS:000282869800008 PM 20967243 ER PT J AU Yu, AA Xing, Y Harrison, SC Kirchhausen, T AF Yu, Anan Xing, Yi Harrison, Stephen C. Kirchhausen, Tomas TI Structural Analysis of the Interaction between Dishevelled2 and Clathrin AP-2 Adaptor, A Critical Step in Noncanonical Wnt Signaling SO STRUCTURE LA English DT Article ID PLANAR CELL POLARITY; EPITHELIAL POLARIZATION; ENDOCYTIC TRAFFICKING; SORTING SIGNALS; DROSOPHILA EYE; DEP-DOMAIN; WINGLESS; PROTEINS; RECOGNITION; SPECIFICITY AB Wnt association with its receptor, Frizzled (Fz), and recruitment by the latter of an adaptor, Dishevelled (Dvl), initiates signaling through at least two distinct pathways ("canonical" and "noncanonical"). Endocytosis and compartmentalization help determine the signaling outcome. Our previous work has shown that Dvl2 links at least one Frizzled family member (Fz4) to clathrin-mediated endocytosis by interacting with the mu 2 subunit of the AP-2 clathrin adaptor, through both a classical endocytic tyrosine motif and a so-called "DEP domain." We report here the crystal structure of a chimeric protein that mimics the Dvl2-mu 2 complex. The DEP domain binds at one end of the elongated, C-terminal domain of mu 2. This domain:domain interface shows that parts of the mu 2 surface distinct from the tyrosine-motif site can help recruit specific receptors or adaptors into a clathrin coated pit. Mutation of residues at the DEP-mu 2 contact or in the tyrosine motif reduce affinity of Dvl2 for mu 2 and block efficient internalization of Fz4 in response to ligation by Wnt5a. The crystal structure has thus allowed us to identify the specific interaction that leads to Frizzled uptake and to downstream, noncanonical signaling events. C1 [Yu, Anan; Kirchhausen, Tomas] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. [Yu, Anan; Kirchhausen, Tomas] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA 02115 USA. [Xing, Yi; Harrison, Stephen C.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Jack & Eileen Connors Struct Biol Lab, Boston, MA 02115 USA. [Harrison, Stephen C.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA. RP Kirchhausen, T (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA 02115 USA. EM kirchhausen@crystal.harvard.edu FU NIH [GM36548, 075252, U54 AI057159]; Ruth Kirschstein National Research Service FX We thank the staff of the Northeast Collaborative Access Team at the Advanced Photon Source for assistance with X-ray diffraction data collection, Kevin Corbett for collecting diffraction data, Iris Rapoport, Werner Boll, and Till Backing for AP-2 preparations and Eric Marino for maintaining the fluorescence microscopy resource. The research was supported by NIH grant GM36548, 075252, and U54 AI057159 (NERCE Imaging Resource) (to T.K.). Y.X. acknowledges a Ruth Kirschstein National Research Service Award. S.C.H. is an Investigator in the Howard Hughes Medical Institute. NR 38 TC 27 Z9 30 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0969-2126 J9 STRUCTURE JI Structure PD OCT 13 PY 2010 VL 18 IS 10 BP 1311 EP 1320 DI 10.1016/j.str.2010.07.010 PG 10 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 668KS UT WOS:000283268500015 PM 20947020 ER PT J AU Smith, EE Shobha, N Dai, D Olson, DM Reeves, MJ Saver, JL Hernandez, AF Peterson, ED Fonarow, GC Schwamm, LH AF Smith, Eric E. Shobha, Nandavar Dai, David Olson, DaiWai M. Reeves, Mathew J. Saver, Jeffrey L. Hernandez, Adrian F. Peterson, Eric D. Fonarow, Gregg C. Schwamm, Lee H. TI Risk Score for In-Hospital Ischemic Stroke Mortality Derived and Validated Within the Get With The Guidelines-Stroke Program SO CIRCULATION LA English DT Article DE stroke; cerebral stroke; mortality; prognosis ID QUALITY-OF-CARE; SEX-DIFFERENCES; COMORBIDITY ADJUSTMENT; PROGNOSTIC MODELS; CASE-FATALITY; SCALE SCORE; PREDICTION; SURVIVAL; OUTCOMES; REGISTRY AB Background-There are few validated models for prediction of in-hospital mortality after ischemic stroke. We used Get With the Guidelines-Stroke Program data to derive and validate prediction models for a patient's risk of in-hospital ischemic stroke mortality. Methods and Results-Between October 2001 and December 2007, there were 1036 hospitals that contributed 274 988 ischemic stroke patients to this study. The sample was randomly divided into a derivation (60%) and validation (40%) sample. Logistic regression was used to determine the independent predictors of mortality and to assign point scores for a prediction model. We also separately derived and validated a model in the 109 187 patients (39.7%) with a National Institutes of Health Stroke Scale (NIHSS) score recorded. Model discrimination was quantified by calculating the C statistic from the validation sample. In-hospital mortality was 5.5% overall and 5.2% in the subset in which NIHSS score was recorded. Characteristics associated with in-hospital mortality were age, arrival mode (eg, via ambulance versus other mode), history of atrial fibrillation, previous stroke, previous myocardial infarction, carotid stenosis, diabetes mellitus, peripheral vascular disease, hypertension, history of dyslipidemia, current smoking, and weekend or night admission. The C statistic was 0.72 in the overall validation sample and 0.85 in the model that included NIHSS score. A model with NIHSS score alone provided nearly as good discrimination (C statistic 0.83). Plots of observed versus predicted mortality showed excellent model calibration in the validation sample. Conclusions-The Get With the Guidelines-Stroke risk model provides clinicians with a well-validated, practical bedside tool for mortality risk stratification. The NIHSS score provides substantial incremental information on a patient's short-term mortality risk and is the strongest predictor of mortality. (Circulation. 2010;122:1496-1504.) C1 [Smith, Eric E.] Univ Calgary, Dept Clin Neurosci, Calgary Stroke Program, Foothills Med Ctr,Hotchkiss Brain Inst, Calgary, AB T2N 2T9, Canada. [Dai, David; Olson, DaiWai M.; Hernandez, Adrian F.; Peterson, Eric D.] Duke Clin Res Inst, Durham, NC USA. [Reeves, Mathew J.] Michigan State Univ, Dept Epidemiol, E Lansing, MI 48824 USA. [Saver, Jeffrey L.] Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90024 USA. [Fonarow, Gregg C.] Univ Calif Los Angeles, Div Cardiol, Los Angeles, CA USA. [Schwamm, Lee H.] Massachusetts Gen Hosp, Stroke Serv, Boston, MA 02114 USA. RP Smith, EE (reprint author), Univ Calgary, Dept Clin Neurosci, Calgary Stroke Program, Foothills Med Ctr,Hotchkiss Brain Inst, 1403 29th St NW, Calgary, AB T2N 2T9, Canada. EM eesmith@ucalgary.ca RI Hernandez, Adrian F./A-7818-2016; OI Schwamm, Lee/0000-0003-0592-9145; Hernandez, Adrian F./0000-0003-3387-9616; Smith, Eric/0000-0003-3956-1668; Saver, Jeffrey/0000-0001-9141-2251 FU Boehringer-Ingelheim; Merck FX The GWTG-Stroke program is provided by the American Heart Association/ American Stroke Association. The GWTG-Stroke program is currently supported in part by a charitable contribution from Bristol-Myers Squibb/Sanofi Pharmaceutical Partnership and the American Heart Association Pharmaceutical Roundtable. GWTG-Stroke has been funded in the past through support from Boehringer-Ingelheim and Merck. These funding agencies did not participate in design or analysis, manuscript preparation, or approval of this study. NR 41 TC 101 Z9 106 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 12 PY 2010 VL 122 IS 15 BP 1496 EP 1504 DI 10.1161/CIRCULATIONAHA.109.932822 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 661SS UT WOS:000282749000013 PM 20876438 ER PT J AU Thompson, BB Bejot, Y Caso, V Castillo, J Christensen, H Flaherty, ML Foerch, C Ghandehari, K Giroud, M Greenberg, SM Hallevi, H Hemphill, JC Heuschmann, P Juvela, S Kimura, K Myint, PK Nagakane, Y Naritomi, H Passero, S Rodriguez-Yanez, MR Roquer, J Rosand, J Rost, NS Saloheimo, P Salomaa, V Sivenius, J Sorimachi, T Togha, M Toyoda, K Turaj, W Vemmos, KN Wolfe, CDA Woo, D Smith, EE AF Thompson, B. B. Bejot, Y. Caso, V. Castillo, J. Christensen, H. Flaherty, M. L. Foerch, C. Ghandehari, K. Giroud, M. Greenberg, S. M. Hallevi, H. Hemphill, J. C., III Heuschmann, P. Juvela, S. Kimura, K. Myint, P. K. Nagakane, Y. Naritomi, H. Passero, S. Rodriguez-Yanez, M. R. Roquer, J. Rosand, J. Rost, N. S. Saloheimo, P. Salomaa, V. Sivenius, J. Sorimachi, T. Togha, M. Toyoda, K. Turaj, W. Vemmos, K. N. Wolfe, C. D. A. Woo, D. Smith, E. E. TI Prior antiplatelet therapy and outcome following intracerebral hemorrhage A systematic review SO NEUROLOGY LA English DT Review ID CASE-FATALITY RATES; INDEPENDENT PREDICTOR; CONTROLLED-TRIAL; STROKE REGISTRY; ISCHEMIC-STROKE; EARLY DEATH; MORTALITY; POPULATION; ASPIRIN; RISK AB Objectives: Antiplatelet therapy (APT) promotes bleeding; therefore, APT might worsen outcome in patients with intracerebral hemorrhage (ICH). We performed a systematic review and meta-analysis to address the hypothesis that pre-ICH APT use is associated with mortality and poor functional outcome following ICH. Methods: The Medline and Embase databases were searched in February 2008 using relevant key words, limited to human studies in the English language. Cohort studies of consecutive patients with ICH reporting mortality or functional outcome according to pre-ICH APT use were identified. Of 2,873 studies screened, 10 were judged to meet inclusion criteria by consensus of 2 authors. Additionally, we solicited unpublished data from all authors of cohort studies with >100 patients published within the last 10 years, and received data from 15 more studies. Univariate and multivariable-adjusted odds ratios (ORs) for mortality and poor functional outcome were abstracted as available and pooled using a random effects model. Results: We obtained mortality data from 25 cohorts (15 unpublished) and functional outcome data from 21 cohorts (14 unpublished). Pre-ICH APT users had increased mortality in both univariate (OR 1.41, 95% confidence interval [CI] 1.21 to 1.64) and multivariable-adjusted (OR 1.27, 95% CI 1.10 to 1.47) pooled analyses. By contrast, the pooled OR for poor functional outcome was no longer significant when using multivariable-adjusted estimates (univariate OR 1.29, 95% CI 1.09 to 1.53; multivariable-adjusted OR 1.10, 95% CI 0.93 to 1.29). Conclusions: In cohort studies, APT use at the time of ICH compared to no APT use was independently associated with increased mortality but not with poor functional outcome. Neurology (R) 2010;75:1333-1342 C1 [Smith, E. E.] Univ Calgary, Foothills Med Ctr, Dept Clin Neurosci, Calgary, AB T2N 2T9, Canada. [Thompson, B. B.] Brown Univ, Dept Neurol, Providence, RI 02912 USA. [Thompson, B. B.] Brown Univ, Dept Neurosurg, Providence, RI 02912 USA. [Caso, V.] Osped Santa Maria Misericordia, Stroke Unit, Perugia, Italy. [Castillo, J.; Rodriguez-Yanez, M. R.] Univ Santiago, Hosp Clin, Dept Neurol, Santiago De Compostela, Spain. [Christensen, H.] Univ Copenhagen, Dept Neurol, Bispebjerg Hosp, DK-1168 Copenhagen, Denmark. [Flaherty, M. L.; Woo, D.] Univ Cincinnati, Acad Hlth Ctr, Dept Neurol, Cincinnati, OH 45221 USA. [Foerch, C.] Goethe Univ Frankfurt, Dept Neurol, Frankfurt, Germany. [Ghandehari, K.] Mashhad Univ Med Sci, Ghaem Hosp, Dept Neurol, Mashhad, Iran. [Giroud, M.] INSERM, Stroke Registry Dijon, F-75654 Paris 13, France. [Greenberg, S. M.; Rosand, J.; Rost, N. S.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Hallevi, H.] Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, Dept Neurol, IL-69978 Tel Aviv, Israel. [Hemphill, J. C., III] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Wolfe, C. D. A.] Kings Coll London, Div Hlth & Social Care Res, R&D Guys & St Thomas Fdn Trust, London, England. [Heuschmann, P.] Charite Univ Med Berlin, Ctr Stroke Res Berlin, Berlin, Germany. [Juvela, S.] Turku Univ, Cent Hosp, Dept Neurosurg, Turku, Finland. [Kimura, K.] Kawasaki Med Univ, Dept Stroke Med, Kurashiki, Okayama, Japan. [Myint, P. K.] Univ E Anglia, Sch Med Hlth Policy & Practice, Norwich NR4 7TJ, Norfolk, England. [Myint, P. K.] Norfolk & Norwich Univ Hosp, Dept Med Elderly, Norwich NR4 7TJ, Norfolk, England. [Nagakane, Y.; Naritomi, H.; Toyoda, K.] Natl Cerebral & Cardiovasc Ctr, Dept Cerebrovasc Med, Osaka, Japan. [Passero, S.] Univ Siena, Neurol Unit, Dept Neurosci, I-53100 Siena, Italy. [Roquer, J.] Hosp del Mar, Unitat Ietus, Barcelona, Spain. [Saloheimo, P.] Univ Oulu, Dept Neurol, Oulu, Finland. [Saloheimo, P.] Kellokoski Hosp, Dept Neuropsychiat & Psychogeriatr, Tuusula, Finland. [Salomaa, V.] KTL Natl Publ Hlth Inst, Dept Epidemiol & Hlth Promot, Helsinki, Finland. [Sivenius, J.] Kuopio Univ Hosp, Brain Res & Rehabil Ctr Neuron, SF-70210 Kuopio, Finland. [Sorimachi, T.] Niigata Univ, Brain Res Inst, Dept Neurosurg, Niigata 95021, Japan. [Togha, M.] Univ Tehran Med Sci, Sina Hosp, Dept Neurol, Tehran, Iran. [Turaj, W.] Jagiellonian Univ, Coll Med, Dept Neurol, Krakow, Poland. [Vemmos, K. N.] Univ Athens, Sch Med, Alexandra Hosp, Dept Clin Therapeut,Acute Stroke Unit, GR-11527 Athens, Greece. RP Smith, EE (reprint author), Univ Calgary, Foothills Med Ctr, Dept Clin Neurosci, Rm C1212,1403 29 St NW, Calgary, AB T2N 2T9, Canada. EM eesmith@ucalgary.ca RI Roquer, Jaume/D-9483-2011; Toyoda, Kazunori/J-3828-2015; OI Toyoda, Kazunori/0000-0002-8346-9845; Castillo, Jose/0000-0002-6685-3001; Smith, Eric/0000-0003-3956-1668 FU Boehringer Ingelheim; Augustinusfonden; NIH [NINDS 2P50NS044283, NINDS R01 NS030678, NINDS R01 NS036695, NINDS R01 NS42167, NINDS R01 NS044876, NINDS R01 NS052220, R01AG026484, K24NS056207, R01AG021084, R01NS042147, U54NS057405, R01-NS059727, NINDS 1K23NS064052-01A1, NS36695, NS30678, 5R01NS062028, K23NS046327]; Alzheimer's Association; NIH/NINDS [U10 NS058931]; Novo Nordisk; University of California; European Union; German Stroke Foundation; Stanley Thomas Johnson Foundation; American Heart Association; National Stroke Association; American Stroke Association-Bugher Foundation; Jassen; Oulu University Hospital; Academy of Finland; Finnish Foundation for Cardiovascular Research; Sigrid Juselius Foundation; Ministry of Health, Labour and Welfare; CIHR; Alberta Heritage Fund for Medical Research FX Dr. Thompson, Dr. Be ' jot, Dr. Caso, and Dr. Castillo report no disclosures. Dr. Christensen has received funding for travel from Boehringer Ingelheim and receives research support from Augustinusfonden. Dr. Flaherty receives research support from the NIH (NINDS 2P50NS044283 [PI Project 2]: study drug supplied by Novo Nordisk, NINDS R01 NS030678 [coinvestigator], NINDS R01 NS036695 [coinvestigator], NINDS R01 NS42167 [coinvestigator], NINDS R01 NS044876 [coinvestigator], and NINDS R01 NS052220 [coinvestigator]. Dr. Foerch is designated as an inventor of a patent re: Use of GFAP for identification of intracerebral haemorrhage, for which he has received royalty payments from Roche. Dr. Ghandehari and Dr. Giroud report no disclosures. Dr. Greenberg serves on scientific advisory boards for Roche and Alzheimer's Immunotherapy; serves on the editorial boards of Neurology, Stroke, Cerebrovascular Disease, and the Journal of Alzheimer's Disease and Other Dementias; has received speaker honoraria from Merck Serono, Esteve, Medtronics, Inc., and Pfizer Inc.; and has received/receives research support from the NIH (R01AG026484 [PI], K24NS056207 [PI], R01AG021084 [coinvestigator], R01NS042147 [PI], and U54NS057405, 2007-2012 [coinvestigator]), and from the Alzheimer's Association. Dr. Hallevi reports no disclosures. Dr. Hemphill serves on the scientific advisory board for Ornim Inc.; serves on the speakers' bureau of the Network for Continuing Medical Education; receives research support from the NIH/NINDS (U10 NS058931 [PI for hub site for Neurological Emergencies Treatment Trials Network]); holds stock in Ornim Inc.; and has provided multiple case reviews and testimony regarding stroke or neurocritical care. During the prior 2 years he previously served on the scientific advisory board of InnerCool Therapies and held stock and stock options in the previous parent company of InnerCool Therapies (Cardium Therapeutics). He also previously received research support from Novo Nordisk and the University of California. Dr. Heuschmann receives/has received research support from the European Union FP7, the German Stroke Foundation, and the Stanley Thomas Johnson Foundation. Dr. Juvela serves as an Associate Editor for the European Journal of Neurology and on the editorial board of Stroke. Dr. Kimura, Dr. Myint, Dr. Nagakane, Dr. Naritomi, Dr. Passero, Dr. Rodriguez-Yanez, and Dr. Roquer report no disclosures. Dr. Rosand has received research support from the NIH [R01-NS059727 (PI)] and from the American Heart Association. Dr. Rost serves as an Associate Editor for Frontiers in Hospitalist Neurology and as an Assistant Editor for Stroke and receives/has received research support from the NIH (NINDS 1K23NS064052-01A1 [PI]), the National Stroke Association, and the American Stroke Association-Bugher Foundation. Dr. Saloheimo has received funding for travel from Jassen; served as an Associate Editor for Duodecim Medical Journal and serves as Associate/Managing Editor for the European Journal of Neurology; received a speaker honorarium from Verve; and has received research support from Oulu University Hospital. Dr. Salomaa serves as an Associate Editor for the European Journal of Cardiovascular Prevention and Rehabilitation and receives research support from the Academy of Finland, the Finnish Foundation for Cardiovascular Research, and the Sigrid Juselius Foundation. Dr. Sivenius, Dr. Sorimachi, and Dr. Togha report no disclosures. Dr. Toyoda receives research support from Grants-in-Aid from the Ministry of Health, Labour and Welfare. Dr.; Turaj serves as a Associate Editor for Neurologia i Neurochirurgia Polska. Dr. Vemmos and Dr. Wolfe report no disclosures. Dr. Woo receives research support from the NIH (NS36695 [coinvestigator] and NS30678 [coinvestigator]). Dr. Smith serves as an Assistant Editor for Stroke; has received speaker honoraria from the Canadian Consortium on Dementia; serves on speakers' bureaus for QuantiaMD and BMJ Best Practice; and has received/receives research support from the NIH (5R01NS062028 [PI] and K23NS046327 [PI]), the CIHR, the Canadian Stroke Network, and Alberta Innovates-Health Solutions (funded by the Alberta Heritage Fund for Medical Research). NR 35 TC 70 Z9 71 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD OCT 12 PY 2010 VL 75 IS 15 BP 1333 EP 1342 PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 663JY UT WOS:000282884500008 PM 20826714 ER PT J AU Attolini, CSO Cheng, YK Beroukhim, R Getz, G Abdel-Wahab, O Levine, RL Mellinghoff, IK Michor, F AF Attolini, Camille Stephan-Otto Cheng, Yu-Kang Beroukhim, Rameen Getz, Gad Abdel-Wahab, Omar Levine, Ross L. Mellinghoff, Ingo K. Michor, Franziska TI A mathematical framework to determine the temporal sequence of somatic genetic events in cancer SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE mathematical modeling; stochastic framework; optimization algorithm ID GROWTH-FACTOR RECEPTOR; MYELOPROLIFERATIVE DISORDERS; TUMOR-SUPPRESSOR; MYELOID MALIGNANCIES; MUTATIONS; TET2; INACTIVATION; PATHWAYS; TRANSFORMATION; GLIOMAGENESIS AB Human cancer is caused by the accumulation of genetic alterations in cells. Of special importance are changes that occur early during malignant transformation because they may result in oncogene addiction and represent promising targets for therapeutic intervention. Here we describe a computational approach, called Retracing the Evolutionary Steps in Cancer (RESIC), to deduce the temporal sequence of genetic events during tumorigenesis from cross-sectional genomic data of tumors at their fully transformed stage. When applied to a dataset of 70 advanced colorectal cancers, our algorithm accurately predicts the sequence of APC, KRAS, and TP53 mutations previously defined by analyzing tumors at different stages of colon cancer formation. We further validate the method with glioblastoma and leukemia sample data and then apply it to complex integrated genomics databases, finding that high-level EGFR amplification appears to be a late event in primary glioblastomas. RESIC represents the first evolutionary mathematical approach to identify the temporal sequence of mutations driving tumorigenesis and may be useful to guide the validation of candidate genes emerging from cancer genome surveys. C1 [Attolini, Camille Stephan-Otto; Cheng, Yu-Kang; Michor, Franziska] Mem Sloan Kettering Canc Ctr, Computat Biol Ctr, New York, NY 10065 USA. [Cheng, Yu-Kang] Weill Cornell Med Coll, Tri Inst Training Program Computat Biol & Med, New York, NY 10065 USA. [Beroukhim, Rameen; Getz, Gad] Broad Inst, Canc Program, Cambridge, MA 02142 USA. [Beroukhim, Rameen] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA. [Beroukhim, Rameen] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Beroukhim, Rameen] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA. [Beroukhim, Rameen] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. [Abdel-Wahab, Omar; Levine, Ross L.; Mellinghoff, Ingo K.] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10065 USA. [Abdel-Wahab, Omar; Levine, Ross L.] Mem Sloan Kettering Canc Ctr, Dept Hematol, New York, NY 10065 USA. [Mellinghoff, Ingo K.] Mem Sloan Kettering Canc Ctr, Dept Neurol, New York, NY 10065 USA. RP Michor, F (reprint author), Mem Sloan Kettering Canc Ctr, Computat Biol Ctr, New York, NY 10065 USA. EM michor@jimmy.harvard.edu OI Stephan-Otto Attolini, Camille/0000-0001-8045-320X; Abdel-Wahab, Omar/0000-0002-3907-6171 FU National Institutes of Health (NIH) [K08CA122833]; Doris Duke Charitable Foundation; V Foundation Scholarship; American Society of Hematology; Memorial Sloan-Kettering Cancer Center (MSKCC); Department of Defense; Sontag Foundation; Sidney Kimmel Foundation; Golfers Against Cancer; Brain Tumors Funders' Collaborative; NIH/National Cancer Institute (NCI); NCI initiative for Physical Sciences in Oncology [U54CA143798] FX The authors thank Timothy Chan, Eric Holland, Marc Ladanyi, Thomas Pfeiffer, David Solit, Barry Taylor, and the Michor lab for critical reading and comments. R. B. was supported by grants from the National Institutes of Health (NIH) (K08CA122833), the Doris Duke Charitable Foundation, and a V Foundation Scholarship. O.A.W. was supported by the American Society of Hematology Research Training Award for Fellows and by the Clinical Scholars Program at Memorial Sloan-Kettering Cancer Center (MSKCC). R. L. L. is an Early Career Award Recipient and is the Geoffrey Beene Junior Chair at Memorial Sloan-Kettering Cancer Center. I. K. M. was supported by the Department of Defense, Sontag Foundation, Doris Duke Charitable Foundation, Sidney Kimmel Foundation, Golfers Against Cancer, and Brain Tumors Funders' Collaborative, and is a Leon Levy Foundation Young Investigator. F. M. was supported by the NIH/National Cancer Institute (NCI) and the MSKCC Society and is a Leon Levy Foundation Young Investigator. This work is supported by the NCI initiative for Physical Sciences in Oncology (physics.cancer.gov) through Award U54CA143798. NR 30 TC 58 Z9 58 U1 0 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 12 PY 2010 VL 107 IS 41 BP 17604 EP 17609 DI 10.1073/pnas.1009117107 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 662LV UT WOS:000282809700031 PM 20864632 ER PT J AU Reite, M Reite, E Collins, D Teale, P Rojas, DC Sandberg, E AF Reite, Martin Reite, Erik Collins, Dan Teale, Peter Rojas, Donald C. Sandberg, Elliot TI Brain size and brain/intracranial volume ratio in major mental illness SO BMC PSYCHIATRY LA English DT Article ID SCHIZOAFFECTIVE DISORDER; BIPOLAR DISORDER; SCHIZOPHRENIA; METAANALYSIS; ENDOPHENOTYPES; MRI; CSF; AGE AB Background: This paper summarizes the findings of a long term study addressing the question of how several brain volume measure are related to three major mental illnesses in a Colorado subject group. It reports results obtained from a large N, collected and analyzed by the same laboratory over a multiyear period, with visually guided MRI segmentation being the primary initial analytic tool. Methods: Intracerebral volume (ICV), total brain volume (TBV), ventricular volume (W), ventricular/brain ratio (VBR), and TBV/ICV ratios were calculated from a total of 224 subject MRIs collected over a period of 13 years. Subject groups included controls (C, N = 89), and patients with schizophrenia (SZ, N = 58), bipolar disorder (BD, N = 51), and schizoaffective disorder (SAD, N = 26). Results: ICV, TBV, and W measures compared favorably with values obtained by other research groups, but in this study did not differ significantly between groups. TBV/ICV ratios were significantly decreased, and VBR increased, in the SZ and BD groups compared to the C group. The SAD group did not differ from C on any measure. Conclusions: In this study TBV/ICV and VBR ratios separated SZ and BD patients from controls. Of interest however, SAD patients did not differ from controls on these measures. The findings suggest that the gross measure of TBV may not reliably differ in the major mental illnesses to a degree useful in diagnosis, likely due to the intrinsic variability of the measures in question; the differences in VBR appear more robust across studies. Differences in some of these findings compared to earlier reports from several laboratories finding significant differences between groups in W and TBV may relate to phenomenological drift, differences in analytic techniques, and possibly the "file drawer problem". C1 [Reite, Martin; Collins, Dan; Teale, Peter; Rojas, Donald C.] Univ Colorado Denver, Dept Psychiat, Aurora, CO USA. [Reite, Erik] Eglin AFB Hosp, Ft Walton Beach, FL USA. [Sandberg, Elliot] Denver VAMC, Dept Radiol, Denver, CO USA. RP Reite, M (reprint author), Univ Colorado Denver, Dept Psychiat, Aurora, CO USA. EM martin.reite@ucdenver.edu RI Rojas, Don/F-4296-2012; OI Rojas, Don/0000-0001-6560-9616 FU USPHS [MH47476, MH64502, MH 088623]; NIH FX This research was supported by USPHS grants No. MH47476, MH64502, and 088623; MR was Principal Investigator on the NIH grants that funded this research, and was responsible for the overall design and interpretation of the findings. ER personally segmented all MRI structures over the course of the study, and contributed to the literature review and discussion of how these findings relate to previously published findings by other laboratories. DC initiated and performed those computer analytic techniques used to clarify and improve resolution of several of the brain volume variable, and maintained the final data base contributing to the manuscript. PT supervised overall accuracy and comparability of imaging across the several MRI laboratories, and contributed to the final data analysis and manuscript preparation. DR was responsible for supervision of experimental design and final data analysis. ES was responsible for training in neuroanatomy and monitoring accuracy of image outlines. All authors have read and approved the final manuscript.. NR 36 TC 6 Z9 6 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-244X J9 BMC PSYCHIATRY JI BMC Psychiatry PD OCT 11 PY 2010 VL 10 AR 79 DI 10.1186/1471-244X-10-79 PG 9 WC Psychiatry SC Psychiatry GA 668ZJ UT WOS:000283315400001 PM 20937136 ER PT J AU Zhu, CQ Ding, KY Strumpf, D Weir, BA Meyerson, M Pennell, N Thomas, RK Naoki, K Ladd-Acosta, C Liu, N Pintilie, M Der, S Seymour, L Jurisica, I Shepherd, FA Tsao, MS AF Zhu, Chang-Qi Ding, Keyue Strumpf, Dan Weir, Barbara A. Meyerson, Matthew Pennell, Nathan Thomas, Roman K. Naoki, Katsuhiko Ladd-Acosta, Christine Liu, Ni Pintilie, Melania Der, Sandy Seymour, Lesley Jurisica, Igor Shepherd, Frances A. Tsao, Ming-Sound TI Prognostic and Predictive Gene Signature for Adjuvant Chemotherapy in Resected Non-Small-Cell Lung Cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID EXPRESSION SIGNATURES; SQUAMOUS-CELL; P53 PROTEIN; SURVIVAL; ADENOCARCINOMA; MDM2; DEPENDENCE AB Purpose The JBR. 10 trial demonstrated benefit from adjuvant cisplatin/vinorelbine (ACT) in early-stage non-small-cell lung cancer (NSCLC). We hypothesized that expression profiling may identify stage-independent subgroups who might benefit from ACT. Patients and Methods Gene expression profiling was conducted on mRNA from 133 frozen JBR. 10 tumor samples (62 observation [OBS], 71 ACT). The minimum gene set that was selected for the greatest separation of good and poor prognosis patient subgroups in OBS patients was identified. The prognostic value of this gene signature was tested in four independent published microarray data sets and by quantitative reverse-transcriptase polymerase chain reaction (RT-qPCR). Results A 15-gene signature separated OBS patients into high-risk and low-risk subgroups with significantly different survival (hazard ratio [HR], 15.02; 95% CI, 5.12 to 44.04; P <.001; stage I HR, 13.31; P <.001; stage II HR, 13.47; P <.001). The prognostic effect was verified in the same 62 OBS patients where gene expression was assessed by qPCR. Furthermore, it was validated consistently in four separate microarray data sets (total 356 stage IB to II patients without adjuvant treatment) and additional JBR. 10 OBS patients by qPCR (n = 19). The signature was also predictive of improved survival after ACT in JBR. 10 high-risk patients (HR, 0.33; 95% CI, 0.17 to 0.63; P = .0005), but not in low-risk patients (HR, 3.67; 95% CI, 1.22 to 11.06; P =.0133; interaction P <.001). Significant interaction between risk groups and ACT was verified by qPCR. Conclusion This 15-gene expression signature is an independent prognostic marker in early-stage, completely resected NSCLC, and to our knowledge, is the first signature that has demonstrated the potential to select patients with stage IB to II NSCLC most likely to benefit from adjuvant chemotherapy with cisplatin/vinorelbine. J Clin Oncol 28:4417-4424. (C) 2010 by American Society of Clinical Oncology C1 [Tsao, Ming-Sound] Princess Margaret Hosp, Toronto, ON M5G 2M9, Canada. Ontario Canc Inst, Univ Hlth Network, Toronto, ON M4X 1K9, Canada. Univ Toronto, Toronto, ON, Canada. Canada Clin Trials Grp, Natl Canc Inst, Kingston, ON, Canada. Queens Univ, Kingston, ON, Canada. Dana Farber Canc Inst, Ctr Canc Genome Discovery, Boston, MA 02115 USA. MIT, Broad Inst, Cambridge, MA 02139 USA. Max Planck Soc, Klaus Joachim Zuich Lab, Max Planck Inst Neurol Res, Cologne, Germany. Univ Cologne, Fac Med, Cologne, Germany. RP Tsao, MS (reprint author), Princess Margaret Hosp, Rm 7-613,610 Univ Ave, Toronto, ON M5G 2M9, Canada. EM Ming.Tsao@uhn.on.ca RI Meyerson, Matthew/E-7123-2012; Mendez, Pedro /J-8955-2016 OI Mendez, Pedro /0000-0001-6713-7907 FU Canadian Cancer Society; US National Cancer Institute; Canada Foundation for Innovation [12301, 203383]; Canada Research Chair; Ontario Ministry of Health and Long Term Care FX Supported by grants from the Canadian Cancer Society (clinical trial, microarray data and correlative analysis), the US National Cancer Institute (microarray studies), Grants No. 12301 and 203383 from the Canada Foundation for Innovation (lab infrastructure), and the Canada Research Chair Program (I. J.). This research was funded in part by the Ontario Ministry of Health and Long Term Care. We thank GlaxoSmithKline for supporting the establishment of the JBR. 10 frozen tumor bank. NR 36 TC 183 Z9 185 U1 2 U2 13 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 OCT 10 PY 2010 VL 28 IS 29 BP 4417 EP 4424 DI 10.1200/JCO.2009.26.4325 PG 8 WC Oncology SC Oncology GA 660LG UT WOS:000282643600029 PM 20823422 ER PT J AU Wright, AA Keating, NL Balboni, TA Matulonis, UA Block, SD Prigerson, HG AF Wright, Alexi A. Keating, Nancy L. Balboni, Tracy A. Matulonis, Ursula A. Block, Susan D. Prigerson, Holly G. TI Place of Death: Correlations With Quality of Life of Patients With Cancer and Predictors of Bereaved Caregivers' Mental Health SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID INTENSIVE-CARE-UNIT; FAMILY-MEMBERS; MEDICARE BENEFICIARIES; POSTTRAUMATIC STRESS; COMPLICATED GRIEF; ILL PATIENTS; NEAR-DEATH; PEOPLE DIE; END; AGGRESSIVENESS AB Purpose To determine whether the place of death for patients with cancer is associated with patients' quality of life (QoL) at the end of life (EOL) and psychiatric disorders in bereaved caregivers. Patients and Methods Prospective, longitudinal, multisite study of patients with advanced cancer and their caregivers (n = 342 dyads). Patients were followed from enrollment to death, a median of 4.5 months later. Patients' QoL at the EOL was assessed by caregiver report within 2 weeks of death. Bereaved caregivers' mental health was assessed at baseline and 6 months after loss with the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, and the Prolonged Grief Disorder interview. Results In adjusted analyses, patients with cancer who died in an intensive care unit (ICU) or hospital experienced more physical and emotional distress and worse QoL at the EOL (all P <=.03), compared with patients who died at home with hospice. ICU deaths were associated with a heightened risk for posttraumatic stress disorder, compared with home hospice deaths (21.1% [four of 19] v 4.4% [six of 137]; adjusted odds ratio [AOR], 5.00; 95% CI, 1.26 to 19.91; P=.02), after adjustment for caregivers' preexisting psychiatric illnesses. Similarly, hospital deaths were associated with a heightened risk for prolonged grief disorder (21.6% [eight of 37] v 5.2% [four of 77], AOR, 8.83; 95% CI, 1.51 to 51.77; P=.02), compared with home hospice deaths. Conclusion Patients with cancer who die in a hospital or ICU have worse QoL compared with those who die at home, and their bereaved caregivers are at increased risk for developing psychiatric illness. Interventions aimed at decreasing terminal hospitalizations or increasing hospice utilization may enhance patients' QoL at the EOL and minimize bereavement-related distress. J Clin Oncol 28:4457-4464. (C) 2010 by American Society of Clinical Oncology C1 [Wright, Alexi A.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Wright, AA (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St,Smith 333, Boston, MA 02115 USA. EM alexi_wright@dfci.harvard.org FU National Institute of Mental Health [MH63892]; National Cancer Institute [CA 106370, 5R25CA092203]; National Palliative Care Research Center; Dana-Farber Cancer Institute Center for Psycho-Oncology and Palliative Care Research; Susan G. Komen for the Cure FX Supported in part by the following grants to H.G.P.: Grant No. MH63892 from the National Institute of Mental Health and Grant No. CA 106370 from the National Cancer Institute. Support for A. A. W. was also provided by 5R25CA092203 from the National Cancer Institute, the ASCO Cancer Foundation Young Investigator Award, funded by Susan G. Komen for the Cure, the National Palliative Care Research Center, and the Dana-Farber Cancer Institute Center for Psycho-Oncology and Palliative Care Research. NR 51 TC 201 Z9 202 U1 7 U2 41 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 OCT 10 PY 2010 VL 28 IS 29 BP 4457 EP 4464 DI 10.1200/JCO.2009.26.3863 PG 8 WC Oncology SC Oncology GA 660LG UT WOS:000282643600034 PM 20837950 ER PT J AU Sweeney, CJ Chiorean, EG Verschraegen, CF Lee, FC Jones, S Royce, M Tye, L Liau, KF Bello, A Chao, R Burris, HA AF Sweeney, Christopher J. Chiorean, E. Gabriela Verschraegen, Claire F. Lee, Fa Chyi Jones, Suzanne Royce, Melanie Tye, Lesley Liau, Katherine F. Bello, Akintunde Chao, Richard Burris, Howard A. TI A Phase I Study of Sunitinib Plus Capecitabine in Patients With Advanced Solid Tumors SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID METASTATIC BREAST-CANCER; TYROSINE KINASE INHIBITOR; RENAL-CELL CARCINOMA; ANTITUMOR-ACTIVITY; COLORECTAL-CANCER; GROWTH-FACTOR; LUNG-CANCER; SU11248; THERAPY; MULTICENTER AB Purpose This open-label, phase I, dose-escalation study assessed the maximum-tolerated dose (MTD), safety, pharmacokinetics, and antitumor activity of sunitinib in combination with capecitabine in patients with advanced solid tumors. Patients and Methods Sunitinib (25, 37.5, or 50 mg) was administered orally once daily on three dosing schedules: 4 weeks on treatment, 2 weeks off treatment (Schedule 4/2); 2 weeks on treatment, 1 week off treatment (Schedule 2/1); and continuous daily dosing (CDD schedule). Capecitabine (825, 1,000, or 1,250 mg/m(2)) was administered orally twice daily on days 1 to 14 every 3 weeks for all patients. Sunitinib and capecitabine doses were escalated in serial patient cohorts. Results Seventy-three patients were treated. Grade 3 adverse events included abdominal pain, mucosal inflammation, fatigue, neutropenia, and hand-foot syndrome. The MTD for Schedule 4/2 and the CDD schedule was sunitinib 37.5 mg/d plus capecitabine 1,000 mg/m2 twice per day; the MTD for Schedule 2/1 was sunitinib 50 mg/d plus capecitabine 1,000 mg/m2 twice per day. There were no clinically significant pharmacokinetic drug-drug interactions. Nine partial responses were confirmed in patients with pancreatic cancer (n = 3) and breast, thyroid, neuroendocrine, bladder, and colorectal cancer, and cholangiocarcinoma (each n = 1). Conclusion The combination of sunitinib and capecitabine resulted in an acceptable safety profile in patients with advanced solid tumors. Further evaluation of sunitinib in combination with capecitabine may be undertaken using the MTD for any of the three treatment schedules. J Clin Oncol 28:4513-4520. (C) 2010 by American Society of Clinical Oncology C1 Indiana Univ, Melvin & Bren Simon Canc Ctr, Indianapolis, IN 46204 USA. Sarah Cannon Res Inst, Nashville, TN USA. Univ New Mexico, Albuquerque, NM 87131 USA. Pfizer, La Jolla, CA USA. Pfizer, New York, NY USA. RP Sweeney, CJ (reprint author), Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM Christopher_Sweeney@dfci.harvard.edu FU Pfizer, La Jolla, CA FX Supported by Pfizer, La Jolla, CA.; Suzanne Jones, Pfizer; Melanie Royce, Pfizer Expert NR 33 TC 30 Z9 30 U1 0 U2 1 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 OCT 10 PY 2010 VL 28 IS 29 BP 4513 EP 4520 DI 10.1200/JCO.2009.26.9696 PG 8 WC Oncology SC Oncology GA 660LG UT WOS:000282643600042 PM 20837944 ER PT J AU Lazar, AA Cole, BF Bonetti, M Gelber, RD AF Lazar, Ann A. Cole, Bernard F. Bonetti, Marco Gelber, Richard D. TI Evaluation of Treatment-Effect Heterogeneity Using Biomarkers Measured on a Continuous Scale: Subpopulation Treatment Effect Pattern Plot SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID NEGATIVE BREAST-CANCER; TREATMENT-COVARIATE INTERACTIONS; CLINICAL-TRIALS; POSTMENOPAUSAL WOMEN; SUBGROUP ANALYSES; RANDOMIZED-TRIAL; ESTROGEN-RECEPTOR; PREDICTIVE-VALUE; COMPETING RISK; LETROZOLE AB The discovery of biomarkers that predict treatment effectiveness has great potential for improving medical care, particularly in oncology. These biomarkers are increasingly reported on a continuous scale, allowing investigators to explore how treatment efficacy varies as the biomarker values continuously increase, as opposed to using arbitrary categories of expression levels resulting in a loss of information. In the age of biomarkers as continuous predictors (eg, expression level percentage rather than positive v negative), alternatives to such dichotomized analyses are needed. The purpose of this article is to provide an overview of an intuitive statistical approach-the subpopulation treatment effect pattern plot (STEPP)-for evaluating treatment-effect heterogeneity when a biomarker is measured on a continuous scale. STEPP graphically explores the patterns of treatment effect across overlapping intervals of the biomarker values. As an example, STEPP methodology is used to explore patterns of treatment effect for varying levels of the biomarker Ki-67 in the BIG (Breast International Group) 1-98 randomized clinical trial comparing letrozole with tamoxifen as adjuvant therapy for postmenopausal women with hormone receptor-positive breast cancer. STEPP analyses showed patients with higher Ki-67 values who were assigned to receive tamoxifen had the poorest prognosis and may benefit most from letrozole. J Clin Oncol 28:4539-4544. (C) 2010 by American Society of Clinical Oncology C1 [Gelber, Richard D.] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Univ Vermont, Burlington, VT USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Bocconi Univ, Milan, Italy. RP Gelber, RD (reprint author), Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. EM gelber@jimmy.harvard.edu OI Bonetti, Marco/0000-0003-2304-4180 FU National Institutes of Health [T32 CA-09337, CA-23318, P30-DE-020752, CA-75362]; National Cancer Institute, Bethesda, MD; Italian Ministry of Education, University FX Supported in part by Grants No. T32 CA-09337, CA-23318, P30-DE-020752, and CA-75362 from the National Institutes of Health, National Cancer Institute, Bethesda, MD, and by the Italian Ministry of Education, University, and Research protocol 2007AYHZWC (M. B.). NR 41 TC 44 Z9 45 U1 0 U2 10 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 OCT 10 PY 2010 VL 28 IS 29 BP 4539 EP 4544 DI 10.1200/JCO.2009.27.9182 PG 6 WC Oncology SC Oncology GA 660LG UT WOS:000282643600045 PM 20837942 ER PT J AU Nolting, A Dugast, AS Rihn, S Luteijn, R Carrington, MF Kane, K Jost, S Toth, I Nagami, E Faetkenheuer, G Hartmann, P Altfeld, M Alter, G AF Nolting, Anne Dugast, Anne-Sophie Rihn, Suzannah Luteijn, Rutger Carrington, Mary F. Kane, Katherine Jost, Stephanie Toth, Ildiko Nagami, Ellen Faetkenheuer, Gerd Hartmann, Pia Altfeld, Marcus Alter, Galit TI MHC class I chain-related protein A shedding in chronic HIV-1 infection is associated with profound NK cell dysfunction SO VIROLOGY LA English DT Article DE NK cells; Innate immunity; HIV; Escape ID NATURAL-KILLER-CELLS; T-CELLS; DOWN-REGULATION; NKG2D LIGANDS; EXPRESSION; RECEPTOR; MICA; RECOGNITION; ENGAGEMENT; IMMUNORECEPTOR AB Natural killer (NK) cells play a critical role in host defense against viral infections. However chronic HIV-1 infection is associated with an accumulation of dysfunctional NK cells, that poorly control viral replication. The underlying mechanisms for this NK cell mediated dysfunction are not understood. Certain tumors evade NK cell mediated detection by dampening NK cell activity through the downregulation of NKG2D, via the release of soluble NKG2D-ligands, resulting in a potent suppression of NK cell function. Here we show that chronic HIV-1 infection is associated with a specific defect in NKG2D-mediated NK cell activation, due to reduced expression and transcription of NKG2D. Reduced NKG2D expression was associated with elevated levels of the soluble form of the NKG2D-ligand, MICA, in patient sera, likely released by HIV+CD4+ T cells. Thus, like tumors, HIV-1 may indirectly suppress NK cell recognition of HIV-1-infected CD4+ T cells by enhancing NKG2D-ligand secretion into the serum resulting in a profound impairment of NK cell function. (C) 2010 Elsevier Inc. All rights reserved. C1 [Alter, Galit] MGH MIT & Harvard, Ragon Inst, Massachusetts Gen Hosp, Boston, MA 02129 USA. [Nolting, Anne; Dugast, Anne-Sophie; Rihn, Suzannah; Luteijn, Rutger; Carrington, Mary F.; Kane, Katherine; Jost, Stephanie; Toth, Ildiko; Nagami, Ellen; Altfeld, Marcus; Alter, Galit] Harvard Univ, Ragon Inst, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Nolting, Anne; Faetkenheuer, Gerd; Hartmann, Pia] Univ Hosp Cologne, Dept Infect Dis, Cologne, Germany. RP Alter, G (reprint author), MGH MIT & Harvard, Ragon Inst, Massachusetts Gen Hosp, 149 13th St, Boston, MA 02129 USA. EM galter@partners.org RI Dugast, AnneSophie/L-9541-2015 FU Faculty of Medicine, University of Cologne, Germany; Bill & Melinda Gates Foundation FX This work was supported by the Koeln Fortune Program of the Faculty of Medicine, University of Cologne, Germany (AN), and the Bill & Melinda Gates Foundation (MA). NR 46 TC 26 Z9 29 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 0042-6822 J9 VIROLOGY JI Virology PD OCT 10 PY 2010 VL 406 IS 1 BP 12 EP 20 DI 10.1016/j.virol.2010.05.014 PG 9 WC Virology SC Virology GA 647BA UT WOS:000281589400002 PM 20667578 ER PT J AU Szostak, J Wilson, DS Hobson, A Behrens, T Vidal, M Brasier, M Rayner, S Lewis, N May, R AF Szostak, Jack Wilson, David Sloan Hobson, Allan Behrens, Tim Vidal, Marc Brasier, Martin Rayner, Steve Lewis, Nate May, Robert TI 50 ideas to change science Part one Life and Earth SO NEW SCIENTIST LA English DT Article C1 [Szostak, Jack; Hobson, Allan; Vidal, Marc] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. [Wilson, David Sloan] SUNY Binghamton, Binghamton, NY USA. [Rayner, Steve] Univ Oxford, Inst Sci Innovat & Soc, Said Business Sch, Oxford OX1 2JD, England. [Vidal, Marc] Dana Farber Canc Inst, Ctr Canc Syst Biol, Boston, MA 02115 USA. [Lewis, Nate] CALTECH, Pasadena, CA 91125 USA. RP Szostak, J (reprint author), Harvard Univ, Sch Med, Cambridge, MA 02138 USA. NR 0 TC 0 Z9 0 U1 1 U2 8 PU REED BUSINESS INFORMATION LTD PI SUTTON PA QUADRANT HOUSE THE QUADRANT, SUTTON SM2 5AS, SURREY, ENGLAND SN 0262-4079 J9 NEW SCI JI New Sci. PD OCT 9 PY 2010 VL 208 IS 2781 BP 32 EP 41 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 681TO UT WOS:000284342600029 ER PT J AU Kim, HG Ahn, JW Kurth, I Ullmann, R Kim, HT Kulharya, A Ha, KS Itokawa, Y Meliciani, I Wenzel, W Lee, D Rosenberger, G Ozata, M Bick, DP Sherins, RJ Nagase, T Tekin, M Kim, SH Kim, CH Ropers, HH Gusella, JF Kalscheuer, V Choi, CY Layman, LC AF Kim, Hyung-Goo Ahn, Jang-Won Kurth, Ingo Ullmann, Reinhard Kim, Hyun-Taek Kulharya, Anita Ha, Kyung-Soo Itokawa, Yasuhide Meliciani, Irene Wenzel, Wolfgang Lee, Deresa Rosenberger, Georg Ozata, Metin Bick, David P. Sherins, Richard J. Nagase, Takahiro Tekin, Mustafa Kim, Soo-Hyun Kim, Cheol-Hee Ropers, Hans-Hilger Gusella, James F. Kalscheuer, Vera Choi, Cheol Yong Layman, Lawrence C. TI WDR11, a WD Protein that Interacts with Transcription Factor EMX1, Is Mutated in Idiopathic Hypogonadotropic Hypogonadism and Kallmann Syndrome SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID GONADOTROPIN-RELEASING-HORMONE; METASTASIS-SUPPRESSOR GENE; MENTAL-RETARDATION; TERMINAL DELETION; EMPTY-SPIRACLES; CEREBRAL-CORTEX; MUTATIONS; TRANSLOCATION; RECEPTOR; EXPRESSION AB By defining the chromosomal breakpoint of a balanced 1(10,12) translocation from a subject with Kallmann syndrome and scanning genes in its vicinity in unrelated hypogonadal subjects, we have identified WDR11 as a gene involved in human puberty We found six patients with a total of five different heterozygous WDR11 missense mutations, including three alterations (A435T, R448Q and H690Q) in WD domains important for beta propeller formation and protein-protein interaction In addition, we discovered that WDR11 interacts with EMX1, a homeodomain transcription factor involved in the development of olfactory neurons, and that missense alterations reduce or abolish this interaction. Our findings suggest that impaired pubertal development in these patients results from a deficiency of productive WDR11 protein interaction C1 [Kim, Hyung-Goo; Layman, Lawrence C.] Med Coll Georgia, Sect Reprod Endocrinol Infertil & Genet, Reprod Med & Dev Neurobiol Programs, Dept Obstet & Gynecol,Inst Mol Med & Genet, Augusta, GA 30912 USA. [Kim, Hyung-Goo; Layman, Lawrence C.] Med Coll Georgia, Neurosci Program, Augusta, GA 30912 USA. [Ahn, Jang-Won; Lee, Deresa; Choi, Cheol Yong] Sungkyunkwan Univ, Dept Biol Sci, Suwon 440746, South Korea. [Kurth, Ingo; Rosenberger, Georg] Univ Klinikum Hamburg Eppendorf, Inst Humangenet, D-20246 Hamburg, Germany. [Kim, Hyung-Goo; Ullmann, Reinhard; Ropers, Hans-Hilger; Kalscheuer, Vera] Max Planck Inst Mol Genet, Dept Human Mol Genet, D-14195 Berlin, Germany. [Kim, Hyun-Taek; Kim, Cheol-Hee] Chungnam Natl Univ, Dept Biol, Taejon 305764, South Korea. [Kim, Hyun-Taek; Kim, Cheol-Hee] Chungnam Natl Univ, Grad Sch Analyt Sci & Technolgy, Taejon 305764, South Korea. [Kulharya, Anita] Med Coll Georgia, Dept Pediat, Augusta, GA 30912 USA. [Kulharya, Anita] Med Coll Georgia, Dept Pathol, Augusta, GA 30912 USA. [Ha, Kyung-Soo] Med Coll Georgia, Ctr Canc, Augusta, GA 30912 USA. [Itokawa, Yasuhide; Nagase, Takahiro] Kazusa DNA Res Inst, Dept Human Genome Res, Chiba 2920818, Japan. [Meliciani, Irene; Wenzel, Wolfgang] Forschungszentrum Karlsruhe, Inst Nanotechnol, D-76021 Karlsruhe, Germany. [Ozata, Metin] Gulhane Mil Med Acad, Haydarpasa Training Hosp, Dept Endocrinol, TR-34660 Istanbul, Turkey. [Bick, David P.] Med Coll Wisconsin, Div Med Genet, Dept Pediat, Milwaukee, WI 53226 USA. [Bick, David P.] Med Coll Wisconsin, Dept Obstet & Gynecol, Milwaukee, WI 53226 USA. [Sherins, Richard J.] Columbia Fertil Associates, Washington, DC 20037 USA. [Tekin, Mustafa] Univ Miami, Dr John T Macdonald Fdn, Dept Human Genet, Miller Sch Med, Miami, FL 33156 USA. [Kim, Soo-Hyun] Univ London, Div Basic Med Sci, St Georges Med Sch, London SW17 0RE, England. [Kim, Hyung-Goo; Gusella, James F.] Harvard Univ, Sch Med, Ctr Human Genet Res, Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kim, Hyung-Goo; Gusella, James F.] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02114 USA. [Kurth, Ingo] Jena Univ Hosp, Inst Human Genet, D-07743 Jena, Germany. [Tekin, Mustafa] Ankara Univ, Sch Med, Div Pediat Genet, TR-06610 Ankara, Turkey. RP Kim, HG (reprint author), Med Coll Georgia, Sect Reprod Endocrinol Infertil & Genet, Reprod Med & Dev Neurobiol Programs, Dept Obstet & Gynecol,Inst Mol Med & Genet, 1120 15th St, Augusta, GA 30912 USA. RI Kim, Cheol-Hee/F-6278-2013; Wenzel, Wolfgang/B-3207-2009; OI Wenzel, Wolfgang/0000-0001-9487-4689; Kurth, Ingo/0000-0002-5642-8378; Kalscheuer, Vera/0000-0001-6898-3259 FU Landesstiftung Baden-Wurtemberg; Deutsche Akademische Austauschdienst (German Academic Exchange Service; government of the Republic of Korea [2009-00983]; National Institutes of Health [GM061354, HD33004, HD040287] FX This paper is dedicated to the 80th birthday of Paul G. McDonough We thank all families for their kind participation in this study. We are indebted to the following colleagues for this study. Stefanie Meien, Milton David Stuart, Karen Norris, Ihn-Sik Seong, Jae Ho Lee, Gabriela Alexandru, Wei Chen, Ines Muller, Fer Lan, Hans-Jurgen Kreienkamp, Enno Gossling, Duygu Duman, Lynn Chorich, Sandra Tho, Jill Mokry, Lisa Halvorson, and Temple Smith. We acknowledge support by the Landesstiftung Baden-Wurtemberg, the Deutsche Akademische Austauschdienst (German Academic Exchange Service) and the volunteers of POEM@HOME. This study was supported in part by a Korea Science and Engineering Foundation (KOSEF) grant funded by the government of the Republic of Korea (The Ubiquitome Research Program, 2009-00983 to C Y.C) J.F.G was supported by National Institutes of Health grant GM061354 for the Developmental Genome Anatomy Protect We also acknowledge support to L CL from National Institutes of Health grants HD33004 and HD040287. NR 57 TC 54 Z9 60 U1 0 U2 7 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD OCT 8 PY 2010 VL 87 IS 4 BP 465 EP 479 DI 10.1016/j.ajhg.2010.08.018 PG 15 WC Genetics & Heredity SC Genetics & Heredity GA 665LU UT WOS:000283037600003 PM 20887964 ER PT J AU Goldberg, SI Niemierko, A Shubina, M Turchin, A AF Goldberg, Saveli I. Niemierko, Andrzej Shubina, Maria Turchin, Alexander TI "Summary Page": a novel tool that reduces omitted data in research databases SO BMC MEDICAL RESEARCH METHODOLOGY LA English DT Article ID MISSING DATA; DATA-ENTRY; BONFERRONI PROCEDURE; MULTIPLE TESTS; DATA QUALITY AB Background: Data entry errors are common in clinical research databases. Omitted data are of particular concern because they are more common than erroneously inserted data and therefore could potentially affect research findings. However, few affordable strategies for their prevention are available. Methods: We have conducted a prospective observational study of the effect of a novel tool called "Summary Page" on the frequency of correction of omitted data errors in a radiation oncology research database between July 2008 and March 2009. "Summary Page" was implemented as an optionally accessed screen in the database that visually integrates key fields in the record. We assessed the frequency of omitted data on the example of the Date of Relapse field. We considered the data in this field to be omitted for all records that had empty Date of Relapse field and evidence of relapse elsewhere in the record. Results: A total of 1,156 records were updated and 200 new records were entered in the database over the study period. "Summary Page" was accessed for 44% of all updated records and for 69% of newly entered records. Frequency of correction of the omitted date of cancer relapse was six-fold higher in records for which "Summary Page" was accessed (p = 0.0003). Conclusions: "Summary Page" was strongly associated with an increased frequency of correction of omitted data errors. Further, controlled, studies are needed to confirm this finding and elucidate its mechanism of action. C1 [Goldberg, Saveli I.; Niemierko, Andrzej] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Shubina, Maria; Turchin, Alexander] Brigham & Womens Hosp, Boston, MA 02115 USA. [Turchin, Alexander] Partners HealthCare, Clin Informat Res & Dev, Boston, MA USA. [Niemierko, Andrzej; Turchin, Alexander] Harvard Univ, Sch Med, Boston, MA USA. RP Goldberg, SI (reprint author), Massachusetts Gen Hosp, Boston, MA 02114 USA. EM sigoldberg@partners.org FU Partners IS Research Council FX This study was supported in part by Partners IS Research Council. NR 15 TC 2 Z9 2 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2288 J9 BMC MED RES METHODOL JI BMC Med. Res. Methodol. PD OCT 8 PY 2010 VL 10 AR 91 DI 10.1186/1471-2288-10-91 PG 7 WC Health Care Sciences & Services SC Health Care Sciences & Services GA 669OW UT WOS:000283361100001 PM 20932323 ER PT J AU Das, F Ghosh-Choudhury, N Kasinath, BS Choudhury, GG AF Das, Falguni Ghosh-Choudhury, Nandini Kasinath, Balakuntalam S. Choudhury, Goutam Ghosh TI TGF beta enforces activation of eukaryotic elongation factor-2 (eEF2) via inactivation of eEF2 kinase by p90 ribosomal S6 kinase (p90Rsk) to induce mesangial cell hypertrophy SO FEBS LETTERS LA English DT Article DE Diabetic nephropathy; Receptor serine/threonine kinase; mRNA translation ID MESSENGER-RNA TRANSLATION; DIABETIC-NEPHROPATHY; HIGH GLUCOSE; FIBRONECTIN EXPRESSION; PROTEIN-SYNTHESIS; PROGRESSION; MECHANISMS; SIGNAL; ROLES; MAPK AB eEF2 phosphorylation is under tight control to maintain mRNA translation elongation. We report that TGF beta activates eEF2 by decreasing eEF2 phosphorylation and simultaneously increasing eEF2 kinase phosphorylation. Remarkably, inhibition of Erk1/2 blocked the TGF beta-induced dephosphorylation and phosphorylation of eEF2 and eEF2 kinase. TGF beta increased phosphorylation of p90Rsk in an Erk1/2-dependent manner. Inactive p90Rsk reversed TGF beta-inhibited phosphorylation of eEF2 and suppressed eEF2 kinase activity. Finally, inactive p90Rsk significantly attenuated TGF beta-induced protein synthesis and hypertrophy of mesangial cells. These results present the first evidence that TGF beta utilizes the two layered kinase module Erk/p90Rsk to activate eEF2 for increased protein synthesis during cellular hypertrophy. Published by Elsevier B. V. on behalf of the Federation of European Biochemical Societies. C1 [Das, Falguni; Kasinath, Balakuntalam S.; Choudhury, Goutam Ghosh] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. [Ghosh-Choudhury, Nandini; Kasinath, Balakuntalam S.; Choudhury, Goutam Ghosh] S Texas Vet Hlth Care Syst, VA Res, San Antonio, TX USA. [Choudhury, Goutam Ghosh] S Texas Vet Hlth Care Syst, Geriatr Res Educ & Clin Res, San Antonio, TX USA. [Ghosh-Choudhury, Nandini] Univ Texas Hlth Sci Ctr San Antonio, Dept Pathol, San Antonio, TX 78229 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 NIH [RO1 DK50190, RO1 AR52425, DK 077295, RC2A 036613]; Juvenile Diabetes Research Foundation [1-2008-185]; VA; VA Research Service FX NIH RO1 DK50190 and The Juvenile Diabetes Research Foundation 1-2008-185 Grants to GGC supported this work. GGC is a recipient of VA Senior Research Career Scientist Award and is supported by VA Research Service Merit Review grant. NGC is supported by VA Merit Review and NIH RO1 AR52425 Grants. BSK is supported by Grants from NIH (DK 077295 and RC2A 036613) and VA Research Service. NR 27 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD OCT 8 PY 2010 VL 584 IS 19 BP 4268 EP 4272 DI 10.1016/j.febslet.2010.09.010 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 656TU UT WOS:000282360800025 PM 20837011 ER PT J AU Cho, HH Cahill, CM Vanderburg, CR Scherzer, CR Wang, B Huang, XD Rogers, JT AF Cho, Hyun-Hee Cahill, Catherine M. Vanderburg, Charles R. Scherzer, Clemens R. Wang, Bin Huang, Xudong Rogers, Jack T. TI Selective Translational Control of the Alzheimer Amyloid Precursor Protein Transcript by Iron Regulatory Protein-1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ELEMENT-BINDING PROTEIN; RESPONSIVE-ELEMENT; MESSENGER-RNA; A-BETA; NEURODEGENERATIVE DISEASES; PHOSPHOMIMETIC MUTATION; 5'-UNTRANSLATED REGION; CYTOSOLIC ACONITASE; TARGETED DELETION; ALPHA-SYNUCLEIN AB Iron influx increases the translation of the Alzheimer amyloid precursor protein (APP) via an iron-responsive element (IRE) RNA stem loop in its 5'-untranslated region. Equal modulated interaction of the iron regulatory proteins (IRP1 and IRP2) with canonical IREs controls iron-dependent translation of the ferritin subunits. However, our immunoprecipitation RT-PCR and RNA binding experiments demonstrated that IRP1, but not IRP2, selectively bound the APP IRE in human neural cells. This selective IRP1 interaction pattern was evident in human brain and blood tissue from normal and Alzheimer disease patients. We computer-predicted an optimal novel RNA stem loop structure for the human, rhesus monkey, and mouse APP IREs with reference to the canonical ferritin IREs but also the IREs encoded by erythroid heme biosynthetic aminolevulinate synthase and Hif-2 alpha mRNAs, which preferentially bind IRP1. Selective 2'-hydroxyl acylation analyzed by primer extension analysis was consistent with a 13-base single-stranded terminal loop and a conserved GC-rich stem. Biotinylated RNA probes deleted of the conserved CAGA motif in the terminal loop did not bind to IRP1 relative to wild type probes and could no longer base pair to form a predicted AGA triloop. An AGU pseudo-triloop is key for IRP1 binding to the canonical ferritin IREs. RNA probes encoding the APP IRE stem loop exhibited the same high affinity binding to rhIRP1 as occurs for the H-ferritin IRE (35pM). Intracellular iron chelation increased binding of IRP1 to the APP IRE, decreasing intracellular APP expression in SH-SY5Y cells. Functionally, shRNA knockdown of IRP1 caused increased expression of neural APP consistent with IRP1-APP IRE-driven translation. C1 [Cahill, Catherine M.; Rogers, Jack T.] Harvard Univ, Massachusetts Gen Hosp, Neurochem Lab, Dept Psychiat Neurosci,Sch Med, Charlestown, MA 02129 USA. [Vanderburg, Charles R.] Massachusetts Gen Hosp, Harvard NeuroDiscovery Ctr, Boston, MA 02129 USA. [Wang, Bin] Marshall Univ, Dept Chem, Huntington, WV 25755 USA. [Scherzer, Clemens R.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. [Huang, Xudong] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. RP Cahill, CM (reprint author), Harvard Univ, Massachusetts Gen Hosp, Neurochem Lab, Dept Psychiat Neurosci,Sch Med, Bldg 149,Rm 2510,13th St, Charlestown, MA 02129 USA. EM ccahill@helix.mgh.harvard.edu; jrogers@partners.org FU National Institutes of Health [AG20181]; Alzheimer's Association FX This work was supported, in whole or in part, by National Institutes of Health Grant AG20181 (to J. T. R.). This work was also supported by a Zenith award from the Alzheimer's Association (to J. T. R.). NR 91 TC 50 Z9 52 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD OCT 8 PY 2010 VL 285 IS 41 BP 31217 EP 31232 DI 10.1074/jbc.M110.149161 PG 16 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 661WX UT WOS:000282764600016 PM 20558735 ER PT J AU Centore, RC Havens, CG Manning, AL Li, JM Flynn, RL Tse, A Jin, JP Dyson, NJ Walter, JC Zou, L AF Centore, Richard C. Havens, Courtney G. Manning, Amity L. Li, Ju-Mei Flynn, Rachel Litman Tse, Alice Jin, Jianping Dyson, Nicholas J. Walter, Johannes C. Zou, Lee TI CRL4(Cdt2)-Mediated Destruction of the Histone Methyltransferase Set8 Prevents Premature Chromatin Compaction in S Phase SO MOLECULAR CELL LA English DT Article ID CELL NUCLEAR ANTIGEN; UBIQUITIN LIGASE COMPLEX; H4 LYSINE 20; DNA-DAMAGE; CDT1 DEGRADATION; GENOME INTEGRITY; REPLICATION; METHYLATION; STABILITY; PCNA AB The proper coordination between DNA replication and mitosis during cell-cycle progression is crucial for genomic stability. During G2 and mitosis, Set8 catalyzes monomethylation of histone H4 on lysine 20 (H4K20me1), which promotes chromatin compaction. Set8 levels decline in S phase, but why and how this occurs is unclear. Here, we show that Set8 is targeted for proteolysis in S phase and in response to DNA damage by the E3 ubiquitin ligase, CRL4(Cdt2). Set8 ubiquitylation occurs on chromatin and is coupled to DNA replication via a specific degron in Set8 that binds PCNA. Inactivation of CRL4(Cdt2) leads to Set8 stabilization and aberrant H4K20mel accumulation in replicating cells. Transient S phase expression of a Set8 mutant lacking the degron promotes premature H4K20me1 accumulation and chromatin compaction, and triggers a checkpoint-mediated G2 arrest. Thus, CRL4(Cdt2)-dependent destruction of Set8 in S phase preserves genome stability by preventing aberrant chromatin compaction during DNA synthesis. C1 [Centore, Richard C.; Manning, Amity L.; Flynn, Rachel Litman; Tse, Alice; Dyson, Nicholas J.; Zou, Lee] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. [Zou, Lee] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Havens, Courtney G.; Walter, Johannes C.] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. [Li, Ju-Mei; Jin, Jianping] Univ Texas Hlth Sci Ctr Houston, Dept Biochem & Mol Biol, Houston, TX 77030 USA. RP Zou, L (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA 02129 USA. EM zou.lee@mgh.harvard.edu FU National Institutes of Health (NIH) [GM076388, GM080676, GM081607, F32-GM089150, F32-GM082014]; Welch Foundation [AU-1711]; American Cancer Society FX We thank Drs. Michelle Longworth, James Rocco, William Michaud, Ronald Lebofsky, and Puck Knipscheer for reagents; Dr. Marie Classon and members of the Zou lab for helpful discussions; and Dr. Anindya Dutta for communicating unpublished results. This work is supported by National Institutes of Health (NIH) grants GM076388 (to L.Z.), GM080676 (to J.C.W.), and GM081607 (to N.J.D.). J.J. is a Pew Scholar and supported by a grant (AU-1711) from the Welch Foundation. R.C.C. and C.G.H. are supported by the NIH fellowships F32-GM089150 and F32-GM082014, respectively. A.L.M. and R.L.F. are supported by postdoctoral fellowships from the American Cancer Society. NR 44 TC 109 Z9 110 U1 1 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD OCT 8 PY 2010 VL 40 IS 1 BP 22 EP 33 DI 10.1016/j.molcel.2010.09.015 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 673XP UT WOS:000283697800005 PM 20932472 ER PT J AU Chen, LJ Tam, POS Tham, CCY Liang, XY Chiang, SWY Canlas, O Ritch, R Rhee, DJ Pang, CP AF Chen, Li Jia Tam, Pancy O. S. Tham, Clement C. Y. Liang, Xiao Ying Chiang, Sylvia W. Y. Canlas, Oscar Ritch, Robert Rhee, Douglas J. Pang, Chi Pui TI Evaluation of SPARC as a candidate gene of juvenile-onset primary open-angle glaucoma by mutation and copy number analyses SO MOLECULAR VISION LA English DT Article ID GENOME-WIDE SCAN; CELL-MATRIX INTERACTIONS; TRABECULAR MESHWORK; MATRICELLULAR PROTEIN; HUMAN LENS; LOCUS; MAPS; EXPRESSION; OPTINEURIN; REGION AB Purpose: To investigate the involvement of SPARC (secreted protein acidic and rich in cysteine) mutations and copy number variation in juvenile-onset primary open-angle glaucoma (JPOAG). Methods: This study involved the 27 family members from the GLC1M (glaucoma 1, open angle, M)-linked Philippine pedigree with JPOAG, 46 unrelated Chinese patients with JPOAG and 95 controls. Mutation screening of the SPARC sequence, covering the promoter, 5'-untranslated region (UTR), entire coding regions, exon-intron boundaries, and part of the 3'-UTR, was performed using polymerase chain reaction and direct DNA sequencing. Copy number of the gene was analyzed by three TaqMan copy number assays. Results: No putative SPARC mutation was detected in the Philippine family. In the Chinese participants, 11 sequence variants were detected. Two were novel: IVS2+8G>T and IVS2+32C>T. For the 9 known SNPs, one was synonymous (rs2304052, p. Glu22Glu) and the others were located in noncoding regions. No individual SNP was associated with JPOAG. Five of the most common SNPs, i.e., rs2116780, rs1978707, rs7719521, rs729853, and rs1053411, were contained in a LD (linkage disequilibrium) block. Haplotype-based analysis showed that no haplotype was associated with the disorder. Copy number analysis revealed that all study subjects had two copies of the gene, suggesting no correlation between the copy number of SPARC and JPOAG. Conclusions: We have excluded SPARC as the causal gene at the GLC1M locus in the Philippine pedigree and, for the first time, revealed that the coding sequences, splice sites and copy number of SPARC do not contribute to JPOAG. Further investigations are warranted to unravel the involvement of SPARC in the pathogenesis of other forms of glaucoma. C1 [Chen, Li Jia; Tam, Pancy O. S.; Tham, Clement C. Y.; Liang, Xiao Ying; Chiang, Sylvia W. Y.; Pang, Chi Pui] Chinese Univ Hong Kong, Dept Ophthalmol & Visual Sci, Hong Kong, Hong Kong, Peoples R China. [Canlas, Oscar] Jose B Lingad Mem Reg Hosp, San Fernando, Philippines. [Ritch, Robert] New York Eye & Ear Infirm, Dept Ophthalmol, New York, NY 10003 USA. [Rhee, Douglas J.] Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA USA. RP Pang, CP (reprint author), Chinese Univ Hong Kong, Dept Ophthalmol & Visual Sci, Hong Kong Eye Hosp, 147K Argyle St, Kowloon, Hong Kong, Peoples R China. EM cppang@cuhk.edu.hk RI Chen, Li Jia/I-5078-2014; Pang, Chi/I-5388-2014 OI Chen, Li Jia/0000-0003-3500-5840; FU Endowment Fund for Lim Por-Yen Eye Genetics Research Centre, Hong Kong; General Research Fund, Hong Kong [2140597] FX We express our greatest gratitude to all the participants in this study. The work in this paper was supported in part by the Endowment Fund for Lim Por-Yen Eye Genetics Research Centre, Hong Kong, and research grant 2140597 from the General Research Fund, Hong Kong. NR 66 TC 5 Z9 5 U1 0 U2 4 PU MOLECULAR VISION PI ATLANTA PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E, ATLANTA, GA 30322 USA SN 1090-0535 J9 MOL VIS JI Mol. Vis. PD OCT 8 PY 2010 VL 16 IS 215-19 BP 2016 EP 2025 PG 10 WC Biochemistry & Molecular Biology; Ophthalmology SC Biochemistry & Molecular Biology; Ophthalmology GA 674ED UT WOS:000283716000003 PM 21042566 ER PT J AU Leroux-Roels, I Koutsoukos, M Clement, F Steyaert, S Janssens, M Bourguignon, P Cohen, K Altfeld, M Vandepapeliere, P Pedneault, L McNally, L Leroux-Roels, G Voss, G AF Leroux-Roels, Isabel Koutsoukos, Marguerite Clement, Frederic Steyaert, Sophia Janssens, Michel Bourguignon, Patricia Cohen, Kristen Altfeld, Marcus Vandepapeliere, Pierre Pedneault, Louise McNally, Lisa Leroux-Roels, Geert Voss, Gerald TI Strong and persistent CD4(+) T-cell response in healthy adults immunized with a candidate HIV-1 vaccine containing gp120, Nef and Tat antigens formulated in three Adjuvant Systems SO VACCINE LA English DT Article DE Human immunodeficiency virus; HIV-1 vaccine; Adjuvant; CD4(+) T-cell response ID ACUTE INFECTION; FALCIPARUM-MALARIA; CD8-T-CELL MEMORY; TYPE-1 INFECTION; CD4-T-CELL HELP; PROTEIN VACCINE; VIRAL BURDEN; DOUBLE-BLIND; VIRUS; VIREMIA AB This randomized double-blind study aimed to determine the safety and immunogenicity of a gp120/NefTat candidate human immunodeficiency virus type 1 (HIV-1) vaccine formulated with one of three different Adjuvant Systems (ASO2(A), ASO2(V) and ASO1(B)) in healthy HIV-seronegative adults. All vaccine formulations induced strong HIV-specific CD4(+) T-cell responses characterized by high lympho-proliferative capacity and IL-2 production that were still detectable 18 months after last immunization, with strongest responses seen in the AS01(B) group. Broad coverage was demonstrated against gp120, and to a lesser extent Nef, derived from the most common circulating clades (B, C and circulating recombinant form [CRF]-01). All vaccine formulations exhibited acceptable safety and reactogenicity profiles. The demonstration of superior CIA T-cell induction by AS01(B) provides important guidance for future HIV vaccine development. (C) 2010 Published by Elsevier Ltd. C1 [Koutsoukos, Marguerite; Janssens, Michel; Bourguignon, Patricia; Vandepapeliere, Pierre; Pedneault, Louise; McNally, Lisa; Voss, Gerald] GlaxoSmithKline Biol, Rixensart, Belgium. [Cohen, Kristen; Altfeld, Marcus] Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. [Cohen, Kristen; Altfeld, Marcus] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Cohen, Kristen; Altfeld, Marcus] Harvard Univ, Sch Med, Div Aids, Boston, MA USA. [Leroux-Roels, Isabel; Clement, Frederic; Steyaert, Sophia; Leroux-Roels, Geert] Ghent Univ & Hosp, Ctr Vaccinol, Ghent, Belgium. RP Leroux-Roels, I (reprint author), Ghent Univ Hosp, Ctr Vaccinol, BC001,Pintelaan 185, B-9000 Ghent, Belgium. EM Isabel.LerouxRoels@UGent.be RI Clement, Frederic/B-2204-2009 OI Clement, Frederic/0000-0002-2720-3655 FU GSK Biologicals, Rixensart, Belgium [732461/002/NCT00434512] FX Contributors: All authors contributed towards acquisition of data and/or interpretation of data, writing the manuscript and final decision to submit for publication. GlaxoSmithKline (GSK) Biologicals, Rixensart, Belgium was the study sponsor and was responsible for administration of the study including clinical trial supply management, laboratory assays, study coordination and statistical analyses: Pascale Van Belle, Isabelle Carletti and Alix Collard performed statistical analyses and contributed to critical interpretation of data, Karen Van Uffel was the study monitor, Els de Kock and Evi Ruymaeker were responsible for study management and Fabienne Douad led study data management and cleaning. Emmanuel Hanon (GSK Biologicals) was head of the Human Cellular Immunology group at the time ICS was developed and performed in this trial. Marcelle van Mechelen was head of the group performing CMI analyses (GSK Biologicals). Jennifer Coward provided medical writing assistance. Veronique Delpire and Ulrike Krause provided editorial assistance and publication coordination on behalf of GSK Biologicals. Conflict of interest statement: Marguerite Koutsoukos, Michel Janssens, Patricia Bourguignon, Gerald Voss and Lisa McNally are employees of GSK Biologicals. Pierre Vandepapeliere and Louise Pedneault were GSK employees at the time of study conduct. Funding statement: This study (732461/002/NCT00434512) was coordinated and funded by GSK Biologicals, Rixensart, Belgium. NR 60 TC 43 Z9 43 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD OCT 8 PY 2010 VL 28 IS 43 BP 7016 EP 7024 DI 10.1016/j.vaccine.2010.08.035 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 677DW UT WOS:000283970300010 PM 20728522 ER PT J AU Korsgren, C Lux, SE AF Korsgren, Catherine Lux, Samuel E. TI The carboxyterminal EF domain of erythroid alpha-spectrin is necessary for optimal spectrin-actin binding SO BLOOD LA English DT Article ID BLOOD-CELL MEMBRANE; F-ACTIN; FUNCTIONAL-CHARACTERIZATION; HEREDITARY SPHEROCYTOSIS; GENETIC-DEFECT; PROTEIN 4.1; MECHANISM; COMPLEX; IDENTIFICATION; ORGANIZATION AB Spectrin and protein 4.1R crosslink F-actin, forming the membrane skeleton. Actin and 4.1R bind to one end of beta-spectrin. The adjacent end of alpha-spectrin, called the EF domain, is calmodulin-like, with calcium-dependent and calcium-independent EF hands. The severely anemic sph(1J)/sph(1J) mouse has very fragile red cells and lacks the last 13 amino acids in the EF domain, implying that the domain is critical for skeletal integrity. To test this, we constructed a minispectrin heterodimer from the actin-binding domain, the EF domain, and 4 adjacent spectrin repeats in each chain. The minispectrin bound to F-actin in the presence of native human protein 4.1R. Formation of the spectrin-actin-4.1R complex was markedly attenuated when the minispectrin contained the shortened sph(1J) alpha-spectrin. The alpha-spectrin deletion did not interfere with spectrin heterodimer assembly or 4.1R binding but abolished the binary interaction between spectrin and F-actin. The data show that the alpha-spectrin EF domain greatly amplifies the function of the beta-spectrin actin-binding domain (ABD) in forming the spectrin-actin-4.1R complex. A model, based on the structure of alpha-actinin, suggests that the EF domain modulates the function of the ABD and that the C-terminal EF hands (EF(34)) may bind to the linker that connects the ABD to the first spectrin repeat. (Blood. 2010;116(14):2600-2607) C1 [Korsgren, Catherine; Lux, Samuel E.] Childrens Hosp, Dept Med, Div Hematol Oncol, Boston, MA 02115 USA. [Lux, Samuel E.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. RP Lux, SE (reprint author), Childrens Hosp, Dept Med, Div Hematol Oncol, HU260-1,300 Longwood Ave, Boston, MA 02115 USA. EM lux@enders.tch.harvard.edu FU National Institutes of Health [RO1 HL081608] FX This work was supported by the National Institutes of Health (grant RO1 HL081608). NR 37 TC 10 Z9 10 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD OCT 7 PY 2010 VL 116 IS 14 BP 2600 EP 2607 DI 10.1182/blood-2009-12-260612 PG 8 WC Hematology SC Hematology GA 660MA UT WOS:000282645900029 PM 20585040 ER PT J AU Sacco, A Issa, GC Zhang, Y Liu, Y Maiso, P Ghobrial, IM Roccaro, AM AF Sacco, Antonio Issa, Ghayas C. Zhang, Yong Liu, Yang Maiso, Patricia Ghobrial, Irene M. Roccaro, Aldo M. TI Epigenetic modifications as key regulators of Waldenstrom's Macroglobulinemia biology SO JOURNAL OF HEMATOLOGY & ONCOLOGY LA English DT Review ID MICRORNA EXPRESSION; MULTIPLE-MYELOMA; HUMAN CANCERS; GENE; MODULATION; EPIGENOME; LEUKEMIA; THERAPY; REVEALS; EZH2 AB Waldenstrom's Macroglobulinemia is a low-grade B-cell lymphoma characterized by the presence of lymphoplasmacytic cells in the bone marrow and a monoclonal immunoglobulin M in the circulation. Recent evidences support the hypothesis that epigenetic modifications lead to Waldesntrom cell proliferation and therefore play a crucial role in the pathogenesis of this disease. Indeed, while cytogenetic and gene expression analysis have demonstrated minimal changes; microRNA aberrations and modification in the histone acetylation status of primary Waldenstrom Macroglobulinemia tumor cells have been described. These findings provide a better understanding of the underlying molecular changes that lead to the initiation and progression of this disease. C1 [Sacco, Antonio; Issa, Ghayas C.; Zhang, Yong; Liu, Yang; Maiso, Patricia; Ghobrial, Irene M.; Roccaro, Aldo M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Roccaro, AM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 44 Binney St, Boston, MA 02115 USA. EM aldo_roccaro@dfci.harvard.edu RI Sacco, Antonio/K-4681-2016; OI Sacco, Antonio/0000-0003-2945-9416; Maiso, Patricia/0000-0003-3745-1924; Roccaro, Aldo/0000-0002-1872-5128 NR 31 TC 10 Z9 12 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1756-8722 J9 J HEMATOL ONCOL JI J. Hematol. Oncol. PD OCT 7 PY 2010 VL 3 AR 38 DI 10.1186/1756-8722-3-38 PG 5 WC Oncology; Hematology SC Oncology; Hematology GA 670TG UT WOS:000283449600001 PM 20929526 ER PT J AU Zou, L AF Zou, Lee TI DNA REPAIR A protein giant in its entirety SO NATURE LA English DT Editorial Material ID BRCA2; RECOMBINATION C1 [Zou, Lee] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02129 USA. [Zou, Lee] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02129 USA. RP Zou, L (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Canc, Boston, MA 02129 USA. EM zou.lee@mgh.harvard.edu NR 9 TC 3 Z9 3 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD OCT 7 PY 2010 VL 467 IS 7316 BP 667 EP 668 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 659NE UT WOS:000282572500026 PM 20930833 ER PT J AU Massie, BM O'Connor, CM Metra, M Ponikowski, P Teerlink, JR Cotter, G Weatherley, BD Cleland, JGF Givertz, MM Voors, AA DeLucca, P Mansoor, GA Salerno, CM Bloomfield, DM Dittrich, HC AF Massie, Barry M. O'Connor, Christopher M. Metra, Marco Ponikowski, Piotr Teerlink, John R. Cotter, Gad Weatherley, Beth Davison Cleland, John G. F. Givertz, Michael M. Voors, Adriaan A. DeLucca, Paul Mansoor, George A. Salerno, Christina M. Bloomfield, Daniel M. Dittrich, Howard C. CA PROTECT Investigators Comm TI Rolofylline, an Adenosine A(sub 1)-Receptor Antagonist, in Acute Heart Failure. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID WORSENING RENAL-FUNCTION; A(1) RECEPTOR ANTAGONIST; RISK STRATIFICATION; CLINICAL-TRIALS; KIDNEY-FUNCTION; IMPAIRMENT; OUTCOMES; DIAGNOSIS; KW-3902; IMPACT AB Background: Worsening renal function, which is associated with adverse outcomes, often develops in patients with acute heart failure. Experimental and clinical studies suggest that counterregulatory responses mediated by adenosine may be involved. We tested the hypothesis that the use of rolofylline, an adenosine A(sub 1)-receptor antagonist, would improve dyspnea, reduce the risk of worsening renal function, and lead to a more favorable clinical course in patients with acute heart failure. Methods: We conducted a multicenter, double-blind, placebo-controlled trial involving patients hospitalized for acute heart failure with impaired renal function. Within 24 hours after presentation, 2033 patients were randomly assigned, in a 2:1 ratio, to receive daily intravenous rolofylline (30 mg) or placebo for up to 3 days. The primary end point was treatment success, treatment failure, or no change in the patient's clinical condition; this end point was defined according to survival, heart-failure status, and changes in renal function. Secondary end points were the post-treatment development of persistent renal impairment and the 60-day rate of death or readmission for cardiovascular or renal causes. Results: Rolofylline, as compared with placebo, did not provide a benefit with respect to the primary end point (odds ratio, 0.92; 95% confidence interval, 0.78 to 1.09; P=0.35). Persistent renal impairment developed in 15.0% of patients in the rolofylline group and in 13.7% of patients in the placebo group (P=0.44). By 60 days, death or readmission for cardiovascular or renal causes had occurred in similar proportions of patients assigned to rolofylline and placebo (30.7% and 31.9%, respectively; P=0.86). Adverse-event rates were similar overall; however, only patients in the rolofylline group had seizures, a known potential adverse effect of A(sub 1)-receptor antagonists. Conclusions: Rolofylline did not have a favorable effect with respect to the primary clinical composite end point, nor did it improve renal function or 60-day outcomes. It does not show promise in the treatment of acute heart failure with renal dysfunction. (Funded by NovaCardia, a subsidiary of Merck; ClinicalTrials.gov numbers, NCT00328692 and NCT00354458.) N Engl J Med 2010;363:1419-28. C1 [Massie, Barry M.; Teerlink, John R.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Massie, Barry M.; Teerlink, John R.] San Francisco VA Med Ctr, San Francisco, CA USA. [O'Connor, Christopher M.] Duke Univ, Med Ctr, Durham, NC USA. [Cotter, Gad; Weatherley, Beth Davison] Momentum Res, Durham, NC USA. [Metra, Marco] Univ Brescia, Brescia, Italy. [Ponikowski, Piotr] Med Univ, Clin Mil Hosp, Wroclaw, Poland. [Cleland, John G. F.] Univ Hull, Kingston Upon Hull, Yorks, England. [Givertz, Michael M.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Voors, Adriaan A.] Univ Groningen, Groningen, Netherlands. [DeLucca, Paul; Salerno, Christina M.] Merck Res Labs, N Wales, PA USA. [Mansoor, George A.; Bloomfield, Daniel M.] Merck Res Labs, Rahway, NJ USA. [Dittrich, Howard C.] NovaCardia, San Diego, CA USA. RP Massie, BM (reprint author), San Francisco VA Med Ctr 111C, Div Cardiol, 4150 Clement St, San Francisco, CA 94121 USA. EM barry.massie@va.gov RI Teerlink, John/D-2986-2012; Zateyshchikov, Dmitry/D-6575-2012; Vasilieva, Elena/B-2137-2016; Zadionchenko, Vladimir/A-7445-2016; Ponikowski, Piotr/O-6454-2015; OI Zateyshchikov, Dmitry/0000-0001-7065-2045; Zadionchenko, Vladimir/0000-0003-2377-5266; Ponikowski, Piotr/0000-0002-3391-7064; Cleland, John/0000-0002-1471-7016; Metra, Marco/0000-0001-6691-8568 FU NovaCardia, a subsidiary of Merck FX Supported by NovaCardia, a subsidiary of Merck. NR 28 TC 237 Z9 243 U1 1 U2 16 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 7 PY 2010 VL 363 IS 15 BP 1419 EP 1428 DI 10.1056/NEJMoa0912613 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 659NV UT WOS:000282575100007 PM 20925544 ER PT J AU Peleg, AY Hooper, DC AF Peleg, Anton Y. Hooper, David C. TI Hospital-Acquired Infections Due to Gram-Negative Bacteria REPLY SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 [Peleg, Anton Y.] Monash Univ, Melbourne, Vic 3004, Australia. [Hooper, David C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Peleg, AY (reprint author), Monash Univ, Melbourne, Vic 3004, Australia. EM apeleg@bidmc.harvard.edu OI Peleg, Anton/0000-0002-2296-2126 NR 6 TC 3 Z9 3 U1 1 U2 9 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD OCT 7 PY 2010 VL 363 IS 15 BP 1483 EP 1484 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 659NV UT WOS:000282575100024 ER PT J AU Makino, CL Riley, CK Looney, J Crouch, RK Okada, T AF Makino, Clint L. Riley, Charles K. Looney, James Crouch, Rosalie K. Okada, Tetsuji TI Binding of More Than One Retinoid to Visual Opsins SO BIOPHYSICAL JOURNAL LA English DT Article ID PROTEIN-COUPLED RECEPTOR; CRYSTAL-STRUCTURE; SALAMANDER RETINA; CONE OPSINS; RHODOPSIN; PIGMENT; PHOTORECEPTORS; RODS; CHROMOPHORE; REGENERATION AB Visual opsins bind 11-cis retinal at an orthosteric site to form rhodopsins but increasing evidence suggests that at least some are capable of binding an additional retinoid(s) at a separate, allosteric site(s). Microspectrophotometric measurements on isolated, dark-adapted, salamander photoreceptors indicated that the truncated retinal analog, beta-ionone, partitioned into the membranes of green-sensitive rods; however, in blue-sensitive rod outer segments, there was an enhanced uptake of four or more beta-ionones per rhodopsin. X-ray crystallography revealed binding of one beta-ionone to bovine green-sensitive rod rhodopsin. Cocrystallization only succeeded with extremely high concentrations of beta-ionone and binding did not alter the structure of rhodopsin from the inactive state. Salamander green-sensitive rod rhodopsin is also expected to bind beta-ionone at sufficiently high concentrations because the binding site is present on its surface. Therefore, both blue- and green-sensitive rod rhodopsins have at least one allosteric binding site for retinoid, but beta-ionone binds to the latter type of rhodopsin with low affinity and low efficacy. C1 [Makino, Clint L.; Looney, James] Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. [Makino, Clint L.; Looney, James] Harvard Univ, Sch Med, Boston, MA USA. [Riley, Charles K.; Okada, Tetsuji] Gakushuin Univ, Dept Life Sci, Tokyo 171, Japan. [Crouch, Rosalie K.] Med Univ S Carolina, Dept Ophthalmol, Charleston, SC 29425 USA. RP Makino, CL (reprint author), Massachusetts Eye & Ear Infirm, Dept Ophthalmol, Boston, MA 02114 USA. EM cmakino@meei.harvard.edu OI Makino, Clint/0000-0002-6005-9069 FU Lions of Massachusetts [NEI EY011358, EY014104, EY019515, EY04939]; Research to Prevent Blindness; Ministry of Education, Culture, Sports, Science and Technology of Japan [19370071] FX Supported by grant Nos. NEI EY011358, EY014104, EY019515, and EY04939 from the Lions of Massachusetts, an unrestricted grant to the Department of Ophthalmology at the Medical University of South Carolina from Research to Prevent Blindness (RPB, New York), and Grant-in-Aid for Scientific Research (KAKENHI) grant No. 19370071 from the Ministry of Education, Culture, Sports, Science and Technology of Japan. R.K.C. is an RPB senior scientific investigator. NR 55 TC 17 Z9 17 U1 0 U2 8 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD OCT 6 PY 2010 VL 99 IS 7 BP 2366 EP 2373 DI 10.1016/j.bpj.2010.08.003 PG 8 WC Biophysics SC Biophysics GA 662YQ UT WOS:000282850600043 PM 20923672 ER PT J AU Welsh, GI Hale, LJ Eremina, V Jeansson, M Maezawa, Y Lennon, R Pons, DA Owen, RJ Satchell, SC Miles, MJ Caunt, CJ McArdle, CA Pavenstadt, H Tavare, JM Herzenberg, AM Kahn, CR Mathieson, PW Quaggin, SE Saleem, MA Coward, RJM AF Welsh, Gavin I. Hale, Lorna J. Eremina, Vera Jeansson, Marie Maezawa, Yoshiro Lennon, Rachel Pons, Deborah A. Owen, Rachel J. Satchell, Simon C. Miles, Mervyn J. Caunt, Christopher J. McArdle, Craig A. Pavenstaedt, Hermann Tavare, Jeremy M. Herzenberg, Andrew M. Kahn, C. Ronald Mathieson, Peter W. Quaggin, Susan E. Saleem, Moin A. Coward, Richard J. M. TI Insulin Signaling to the Glomerular Podocyte Is Critical for Normal Kidney Function SO CELL METABOLISM LA English DT Article ID DIABETIC-NEPHROPATHY; RECEPTOR; MICE; RESISTANCE; EXPRESSION; INJURY; RHO; NEPHRIN; GTPASES; CELLS AB Diabetic nephropathy (DN) is the leading cause of renal failure in the world. It is characterized by albuminuria and abnormal glomerular function and is considered a hyperglycemic "microvascular" complication of diabetes, implying a primary defect in the endothelium. However, we have previously shown that human podocytes have robust responses to insulin. To determine whether insulin signaling in podocytes affects glomerular function in vivo, we generated mice with specific deletion of the insulin receptor from their podocytes. These animals develop significant albuminuria together with histological features that recapitulate DN, but in a normoglycemic environment. Examination of "normal" insulin-responsive podocytes in vivo and in vitro demonstrates that insulin signals through the MAPK and PI3K pathways via the insulin receptor and directly remodels the actin cytoskeleton of this cell. Collectively, this work reveals the critical importance of podocyte insulin sensitivity for kidney function. C1 [Welsh, Gavin I.; Hale, Lorna J.; Lennon, Rachel; Pons, Deborah A.; Satchell, Simon C.; Mathieson, Peter W.; Saleem, Moin A.; Coward, Richard J. M.] Univ Bristol, Acad Renal Unit, Bristol BS8 1TH, Avon, England. [Tavare, Jeremy M.] Univ Bristol, Sch Biochem, Bristol BS8 1TH, Avon, England. [Owen, Rachel J.; Miles, Mervyn J.] Univ Bristol, Sch Phys, Bristol BS8 1TH, Avon, England. [Caunt, Christopher J.; McArdle, Craig A.] Univ Bristol, Sch Clin Sci, Dept Mol Pharmacol, Bristol BS8 1TH, Avon, England. [Eremina, Vera; Jeansson, Marie; Maezawa, Yoshiro; Quaggin, Susan E.; Coward, Richard J. M.] Univ Toronto, Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. [Pavenstaedt, Hermann] Univ Clin Muenster, Dept Internal Med Nephrol & Hypertens D, D-48149 Munster, Germany. [Herzenberg, Andrew M.] Univ Hlth Network, Dept Pathol, Toronto, ON M5G 2C4, Canada. [Herzenberg, Andrew M.] Univ Toronto, Toronto, ON M5G 2C4, Canada. [Kahn, C. Ronald] Joslin Diabet Ctr, Boston, MA 02215 USA. [Kahn, C. Ronald] Harvard Univ, Sch Med, Boston, MA 02215 USA. RP Coward, RJM (reprint author), Univ Bristol, Acad Renal Unit, Bristol BS8 1TH, Avon, England. EM richard.coward@bristol.ac.uk OI Lennon, Rachel/0000-0001-6400-0227; Miles, Mervyn/0000-0001-7762-6827; Jeansson, Marie/0000-0003-1075-8563; McArdle, Craig/0000-0003-4836-5351 FU Medical Research Council [G0501901]; Wellcome trust; Canadian Diabetes Association [300349]; North Bristol NHS Trust FX R.J.M.C. and L.J.H. are supported by the Medical Research Council (grant number G0501901). The majority of the work presented here was funded by this grant. R.L. and S.C.S. are supported by the Wellcome trust. A.M.H. was supported by Canadian Diabetes Association Operating Grant #300349. Some of this work was supported by a grant awarded by North Bristol NHS Trust. We would like to thank Doug Holmyard, who processed the electron microscopic pictures; Ken Harpal, who prepared the renal histology; and Dionne White, who FAGS sorted the glomerular cells. This work is dedicated to the brilliant Andrew Herzenberg (1971-2010), who was a major driving force within this project. NR 51 TC 163 Z9 166 U1 0 U2 18 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 OCT 6 PY 2010 VL 12 IS 4 BP 329 EP 340 DI 10.1016/j.cmet.2010.08.015 PG 12 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 662TW UT WOS:000282836800009 PM 20889126 ER PT J AU Fehm, MN Huddleston, JI Burke, DW Geller, JA Malchau, H AF Fehm, Michael N. Huddleston, James I. Burke, Dennis W. Geller, Jeffrey A. Malchau, Henrik TI Repair of a Deficient Abductor Mechanism with Achilles Tendon Allograft After Total Hip Replacement SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID ROTATOR-CUFF TEAR; PATELLAR TENDON; ARTHROPLASTY; RECONSTRUCTION; DISLOCATION; ARTHRITIS; AVULSION; RUPTURES; 2-YEAR AB Background: Abductor mechanism insufficiency after total hip arthroplasty is a rare but debilitating problem. The diagnosis is difficult, and when the condition is recognized there are few successful treatment options. The purpose of this study was to review our experience with a surgical technique involving use of a fresh-frozen Achilles tendon allograft with an attached calcaneal bone graft to reconstruct a deficient abductor mechanism after total hip arthroplasty. Methods: From 2003 to 2006, we performed seven abductor reconstructions with an Achilles tendon allograft in patients with abductor deficiency after total hip arthroplasty. At a mean of twenty-nine months after the total hip arthroplasty, all seven patients had symptoms of lateral hip pain and abductor muscle weakness as demonstrated by a Trendelenburg test. The abductor tendon rupture was diagnosed on the basis of an arthrogram and was confirmed at surgery. Results: Before the reconstruction, the average Harris hip score was 34.7 points and the average pain score was 11.4 points. After a minimum duration of follow-up of twenty-four months, the average Harris hip score was 85.9 points and the average pain score was 38.9 points. Conclusions: Abductor reconstruction with an Achilles tendon allograft with a calcaneal bone block attached to the greater trochanter can produce substantial relief of pain, increased abductor muscle strength, decreased limp, and improvements in the Trendelenburg sign and in function at the time of early follow-up. Level of Evidence: Therapeutic Level IV. See Instructions to Authors for a complete description of levels of evidence. C1 [Fehm, Michael N.] Massachusetts Gen Hosp, Dept Orthopaed Surg, Harris Orthopaed Lab, Boston, MA 02114 USA. RP Fehm, MN (reprint author), Massachusetts Gen Hosp, Dept Orthopaed Surg, Harris Orthopaed Lab, Jackson Bldg 1126,55 Fruit St, Boston, MA 02114 USA. EM hmalchau@partners.org NR 23 TC 16 Z9 17 U1 1 U2 5 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 OCT 6 PY 2010 VL 92A IS 13 BP 2305 EP 2311 DI 10.2106/JBJS.I.01011 PG 7 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 675LN UT WOS:000283832300007 PM 20926725 ER PT J AU Boykin, RE Friedman, DJ Higgins, LD Warner, JJP AF Boykin, Robert E. Friedman, Darren J. Higgins, Laurence D. Warner, Jon J. P. TI Suprascapular Neuropathy SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Review ID ROTATOR-CUFF TEARS; TRANSVERSE SCAPULAR LIGAMENT; NERVE ENTRAPMENT SYNDROME; SHOULDER GANGLION CYST; CARPAL-TUNNEL-SYNDROME; SPINOGLENOID NOTCH; VOLLEYBALL PLAYERS; ARTHROSCOPIC DECOMPRESSION; LABRAL TEARS; SUPRASPINATUS MUSCLE C1 [Boykin, Robert E.] Massachusetts Gen Hosp, Yawkey Ctr Outpatient Care, Harvard Shoulder Serv, Boston, MA 02114 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP Boykin, RE (reprint author), Massachusetts Gen Hosp, Yawkey Ctr Outpatient Care, Harvard Shoulder Serv, 55 Fruit St,Suite 3200,3G,Room 3-046, Boston, MA 02114 USA. EM jwarner@partners.org NR 121 TC 46 Z9 47 U1 0 U2 5 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 OCT 6 PY 2010 VL 92A IS 13 BP 2348 EP 2364 DI 10.2106/JBJS.I.01743 PG 17 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 675LN UT WOS:000283832300013 PM 20926731 ER PT J AU Zheng, B Liao, ZX Locascio, JJ Lesniak, KA Roderick, SS Watt, ML Eklund, AC Zhang-James, Y Kim, PD Hauser, MA Grunblatt, E Moran, LB Mandel, SA Riederer, P Miller, RM Federoff, HJ Wullner, U Papapetropoulos, S Youdim, MB Cantuti-Castelvetri, I Young, AB Vance, JM Davis, RL Hedreen, JC Adler, CH Beach, TG Graeber, MB Middleton, FA Rochet, JC Scherzer, CR AF Zheng, Bin Liao, Zhixiang Locascio, Joseph J. Lesniak, Kristen A. Roderick, Sarah S. Watt, Marla L. Eklund, Aron C. Zhang-James, Yanli Kim, Peter D. Hauser, Michael A. Gruenblatt, Edna Moran, Linda B. Mandel, Silvia A. Riederer, Peter Miller, Renee M. Federoff, Howard J. Wuellner, Ullrich Papapetropoulos, Spyridon Youdim, Moussa B. Cantuti-Castelvetri, Ippolita Young, Anne B. Vance, Jeffery M. Davis, Richard L. Hedreen, John C. Adler, Charles H. Beach, Thomas G. Graeber, Manuel B. Middleton, Frank A. Rochet, Jean-Christophe Scherzer, Clemens R. CA Global PD Gene Expression GPEX TI PGC-1 alpha, A Potential Therapeutic Target for Early Intervention in Parkinson's Disease SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article ID LEWY BODY DISEASE; MITOCHONDRIAL COMPLEX-I; SET ENRICHMENT ANALYSIS; NIGRA DOPAMINE NEURONS; BRAAK STAGING SCHEME; SUBSTANTIA-NIGRA; GENE-EXPRESSION; OXIDATIVE STRESS; ALPHA-SYNUCLEIN; BRAIN AB Parkinson's disease affects 5 million people worldwide, but the molecular mechanisms underlying its pathogenesis are still unclear. Here, we report a genome-wide meta-analysis of gene sets (groups of genes that encode the same biological pathway or process) in 410 samples from patients with symptomatic Parkinson's and subclinical disease and healthy controls. We analyzed 6.8 million raw data points from nine genome-wide expression studies, and 185 laser-captured human dopaminergic neuron and substantia nigra transcriptomes, followed by two-stage replication on three platforms. We found 10 gene sets with previously unknown associations with Parkinson's disease. These gene sets pinpoint defects in mitochondrial electron transport, glucose utilization, and glucose sensing and reveal that they occur early in disease pathogenesis. Genes controlling cellular bioenergetics that are expressed in response to peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1 alpha) are underexpressed in Parkinson's disease patients. Activation of PGC-1 alpha results in increased expression of nuclear-encoded subunits of the mitochondrial respiratory chain and blocks the dopaminergic neuron loss induced by mutant alpha-synuclein or the pesticide rotenone in cellular disease models. Our systems biology analysis of Parkinson's disease identifies PGC-1 alpha as a potential therapeutic target for early intervention. C1 [Zheng, Bin; Liao, Zhixiang; Roderick, Sarah S.; Eklund, Aron C.; Scherzer, Clemens R.] Harvard Univ, Sch Med, Ctr Neurol Dis, Lab Neurogen, Cambridge, MA 02139 USA. [Zheng, Bin; Liao, Zhixiang; Roderick, Sarah S.; Eklund, Aron C.; Scherzer, Clemens R.] Brigham & Womens Hosp, Cambridge, MA 02139 USA. [Locascio, Joseph J.; Cantuti-Castelvetri, Ippolita; Young, Anne B.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Lesniak, Kristen A.; Watt, Marla L.; Rochet, Jean-Christophe] Purdue Univ, Dept Med Chem & Mol Pharmacol, W Lafayette, IN 47907 USA. [Eklund, Aron C.] Tech Univ Denmark, Dept Syst Biol, Ctr Biol Sequence Anal, DK-2800 Lyngby, Denmark. [Zhang-James, Yanli] SUNY Upstate Med Univ, Dept Psychiat, Syracuse, NY 13210 USA. [Kim, Peter D.] SUNY Upstate Med Univ, Dept Neurosurg, Syracuse, NY 13210 USA. [Hauser, Michael A.] Duke Univ, Dept Med, Durham, NC 27708 USA. [Gruenblatt, Edna; Riederer, Peter] Univ Wurzburg, Natl Parkinson Fdn, Ctr Excellence Res Lab, D-97070 Wurzburg, Germany. [Mandel, Silvia A.; Youdim, Moussa B.] Technion Israel Inst Technol, Fac Med, Ctr Excellence Neurodegenerat Dis, Eve Topf & Natl Parkinson Fdn, IL-31096 Haifa, Israel. [Miller, Renee M.] Univ Rochester, Ctr Neural Dev & Dis, Rochester, NY 14620 USA. [Federoff, Howard J.] Georgetown Univ, Med Ctr, Dept Neurol, Washington, DC 20007 USA. [Wuellner, Ullrich] Univ Bonn, Dept Neurol, UKB, D-53105 Bonn, Germany. [Papapetropoulos, Spyridon] Univ Miami, Miller Sch Med, Dept Neurol, Miami, FL 33136 USA. [Papapetropoulos, Spyridon] Allergan, Irvine, CA 92623 USA. [Youdim, Moussa B.] Yonsei World Cent Univ, Dept Biol, Seoul 120749, South Korea. [Vance, Jeffery M.] Univ Miami, Miller Sch Med, Hussman Inst Human Genom, Miami, FL 33136 USA. [Davis, Richard L.; Middleton, Frank A.] SUNY Upstate Med Univ, Dept Pathol, Syracuse, NY 13210 USA. [Hedreen, John C.] McLean Hosp, Dept Psychiat, Harvard Brain Tissue Resource Ctr, Belmont, MA 02478 USA. [Adler, Charles H.] Mayo Clin Arizona, Mayo Div Movement Disorders, Scottsdale, AZ 85259 USA. [Beach, Thomas G.] Sun Hlth Res Inst, WH Civin Lab Neuropathol, Sun City, AZ 85259 USA. [Graeber, Manuel B.] Univ Sydney, Brain & Mind Res Inst, Sydney, NSW 2050, Australia. [Scherzer, Clemens R.] Harvard NeuroDiscovery Ctr, Biomarker Program, Cambridge, MA 02139 USA. RP Scherzer, CR (reprint author), Harvard Univ, Sch Med, Ctr Neurol Dis, Lab Neurogen, 65 Landsdowne St,Suite 307A, Cambridge, MA 02139 USA. EM cscherzer@rics.bwh.harvard.edu RI Zheng, Bin/A-6832-2011; Graeber, Manuel/H-3224-2011; Grunblatt, Edna/A-6762-2016 OI Grunblatt, Edna/0000-0001-8505-7265 FU Michael J. Fox Foundation; National Institute on Aging [K08AG024816]; American Federation for Aging Research; NIH [R01NS064155, R21NS060227, P01NS058793, R01NS049221, R24MH068855]; M.E.M.O. Hoffman Foundation; RJG Foundation; Parkinson's Disease Foundation; Parkinson's Disease Society of the UK; Nationales Genomeforschungsnetz (Bundesministerium fur Bildung und Forschung) [01GS0115, TP9]; Brain Net Europe II; Arizona Alzheimer's Disease Core Center, Arizona Biomedical Research Commission, Prescott Family Initiative of the Michael J. Fox Foundation [P30AG19610] FX This work was seeded by an Edmond J. Safra Global Genetics Consortium Award from the Michael J. Fox Foundation (C.R.S.) and supported by a Paul B. Beeson K08AG024816 from the National Institute on Aging and the American Federation for Aging Research (C.R.S.), NIH grants R01NS064155, R21NS060227, and P01NS058793 (all to C.R.S.), NIH grant R01NS049221 (J.-C.R.), the M.E.M.O. Hoffman Foundation (C. R. S.), the RJG Foundation (C.R.S.), the Parkinson's Disease Foundation (J.-C.R.), the Parkinson's Disease Society of the UK (M.B.G.), Nationales Genomeforschungsnetz (Bundesministerium fur Bildung und Forschung 01GS0115; TP9) (U.W.), and Brain Net Europe II (P. R.).; We thank A. J. Ivinson and C. R. Vanderburg (Harvard NeuroDiscovery Center) and B. M. Spiegelman (Dana-Farber Cancer Institute) for insightful comments. We thank the Harvard Brain Tissue Resource Center at McLean Hospital (supported by NIH grant R24MH068855), the Massachusetts Alzheimer Disease Research Center Tissue Resource Center at Massachusetts General Hospital, and the Sun Health Research Institute Brain and Body Donation Program of Sun City, Arizona (supported by P30AG19610 Arizona Alzheimer's Disease Core Center, Arizona Biomedical Research Commission, Prescott Family Initiative of the Michael J. Fox Foundation) for brain samples from subjects with incidental Lewy body disease, PD, and controls. See Supplement for further acknowledgments. NR 66 TC 207 Z9 211 U1 4 U2 31 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 J9 SCI TRANSL MED JI Sci. Transl. Med. PD OCT 6 PY 2010 VL 2 IS 52 AR 52ra73 DI 10.1126/scitranslmed.3001059 PG 14 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 735SV UT WOS:000288438800004 PM 20926834 ER PT J AU Meyer, GS AF Meyer, Gregg S. TI The Social Mission of Medical Education SO ANNALS OF INTERNAL MEDICINE LA English DT Letter C1 [Meyer, Gregg S.] Massachusetts Gen Hosp, Ctr Qual & Safety, Boston, MA 02114 USA. [Meyer, Gregg S.] Massachusetts Gen Phys Org, Boston, MA 02114 USA. RP Meyer, GS (reprint author), Massachusetts Gen Hosp, Ctr Qual & Safety, Boston, MA 02114 USA. NR 1 TC 0 Z9 0 U1 1 U2 1 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 EI 1539-3704 J9 ANN INTERN MED JI Ann. Intern. Med. PD OCT 5 PY 2010 VL 153 IS 7 BP 485 EP 486 DI 10.7326/0003-4819-153-7-201010050-00023 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 658VG UT WOS:000282517000016 PM 20921555 ER PT J AU Moulton, EA Schmahmann, JD Becerra, L Borsook, D AF Moulton, Eric A. Schmahmann, Jeremy D. Becerra, Lino Borsook, David TI The cerebellum and pain: Passive integrator or active participator? SO BRAIN RESEARCH REVIEWS LA English DT Review DE Cerebellum; Pain; Nociception; Nociceptive; Nocifensive; Noxious ID POSITRON-EMISSION-TOMOGRAPHY; NOXIOUS THERMAL-STIMULATION; BRUSH-EVOKED ALLODYNIA; SPINOCEREBELLAR TRACT NEURONS; CHRONIC LOW-BACK; HUMAN BRAIN; PREFRONTAL CORTEX; NEUROPATHIC PAIN; CEREBRAL ACTIVATION; C-FIBER AB The cerebellum is classically considered to be a brain region involved in motor processing, but it has also been implicated in non-motor, and even cognitive, functions. Though previous research suggests that the cerebellum responds to noxious stimuli, its specific role during pain is unclear. Pain is a multidimensional experience that encompasses sensory discriminative, affective motivational, and cognitive evaluative components. Cerebellar involvement during the processing of pain could thus potentially reflect a number of different functional processes. This review will summarize the animal and human research to date that indicates that (1) primary afferents conduct nociceptive (noxious) input to the cerebellum, (2) electrical and pharmacological stimulation of the cerebellum can modulate nociceptive processing, and (3) cerebellar activity occurs during the presence of acute and chronic pain. Possible functional roles for the cerebellum relating to pain will be considered, including perspectives relating to emotion, cognition, and motor control in response to pain. (C) 2010 Elsevier B.V. All rights reserved. C1 [Moulton, Eric A.; Becerra, Lino; Borsook, David] McLean Hosp, Dept Psychiat, Brain Imaging Ctr, PAIN Grp, Belmont, MA 02478 USA. [Moulton, Eric A.; Becerra, Lino; Borsook, David] Harvard Univ, Sch Med, Belmont, MA 02478 USA. [Schmahmann, Jeremy D.] Massachusetts Gen Hosp, Dept Neurol, Ataxia Unit, Boston, MA 02114 USA. [Schmahmann, Jeremy D.] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Moulton, EA (reprint author), McLean Hosp, Dept Psychiat, Brain Imaging Ctr, PAIN Grp, Belmont, MA 02478 USA. EM emoulton@mclean.harvard.edu FU NIDA [DA25289]; NINDS [NS064050]; Birmingham foundation; MINDLink foundation FX This work has been supported by a K01 grant from NIDA to EA (DA25289), a K24 grant from NINDS to DB (NS064050), and the Birmingham foundation and the MINDLink foundation (JDS). The authors declare no conflicts of interest regarding the contents of this manuscript. NR 159 TC 78 Z9 82 U1 0 U2 16 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0173 EI 1872-6321 J9 BRAIN RES REV JI Brain Res. Rev. PD OCT 5 PY 2010 VL 65 IS 1 BP 14 EP 27 DI 10.1016/j.brainresrev.2010.05.005 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 663ZZ UT WOS:000282930000002 PM 20553761 ER PT J AU Lee, JY Park, C Cho, YP Lee, E Kim, H Kim, P Yun, SH Yoon, YS AF Lee, Ji Yoon Park, Changwon Cho, Yong Pil Lee, Eugine Kim, Hyongbum Kim, Pilhan Yun, Seok H. Yoon, Young-sup TI Podoplanin-Expressing Cells Derived From Bone Marrow Play a Crucial Role in Postnatal Lymphatic Neovascularization SO CIRCULATION LA English DT Article DE bone marrow; lymphangiogenesis; lymphatic vessels; Gp38 protein, mouse; podoplanin protein, mouse ID ENDOTHELIAL PROGENITOR CELLS; HEMATOPOIETIC STEM-CELLS; GROWTH-FACTOR-C; TUMOR LYMPHANGIOGENESIS; CD11B(+) MACROPHAGES; IN-VIVO; VESSEL FORMATION; METASTASIS; VEGF; PROMOTES AB Background-Emerging evidence has suggested a contribution of bone marrow (BM) cells to lymphatic vessel formation; however, the exact phenotype of the cells with lymphatic endothelial progenitor cell function has yet to be identified. Here, we investigate the identity of BM-derived lymphatic endothelial progenitor cells and their role in lymphatic neovascularization. Methods and Results-Culture of BM-mononuclear cells in the presence of vascular endothelial growth factors A and C and endothelial growth factor resulted in expression of lymphatic endothelial cell markers. Among these cells, podoplanin(+) cells were isolated by magnetic-activated cell sorting and characterized by fluorescence-activated cell sorter analysis and immunocytochemistry. These podoplanin(+) cells highly express markers for lymphatic endothelial cells, hematopoietic lineages, and stem/progenitor cells; on further cultivation, they generate lymphatic endothelial cells. We further confirmed that podoplanin(+) cells exist in small numbers in BM and peripheral blood of normal mice but are significantly (15-fold) augmented on lymphangiogenic stimuli such as tumor implantation. Next, to evaluate the potential of podoplanin(+) cells for the formation of new lymphatic vessels in vivo, we injected culture-isolated or freshly isolated BM-derived podoplanin(+) cells into wound and tumor models. Immunohistochemistry demonstrated that the injected cells were incorporated into the lymphatic vasculature, displayed lymphatic endothelial cell phenotypes, and increased lymphatic vascular density in tissues, suggesting lymphvasculogenesis. Podoplanin(+) cells also expressed high levels of lymphangiogenic cytokines and increased proliferation of lymphatic endothelial cells during coculture, suggesting a lymphangiogenic or paracrine role. Conclusions-Our results provide compelling evidence that BM-derived podoplanin(+) cells, a previously unrecognized cell type, function as lymphatic endothelial progenitor cells and participate in postnatal lymphatic neovascularization through both lymphvasculogenesis and lymphangiogenesis. (Circulation. 2010;122:1413-1425.) C1 [Lee, Ji Yoon; Park, Changwon; Lee, Eugine; Kim, Hyongbum; Yoon, Young-sup] Emory Univ, Sch Med, Dept Med, Div Cardiol, Atlanta, GA 30332 USA. [Cho, Yong Pil] Univ Ulsan, Coll Med, Dept Vasc Surg, Asan Med Ctr, Seoul, South Korea. [Kim, Pilhan; Yun, Seok H.] Harvard Univ, Sch Med, Boston, MA USA. [Kim, Pilhan; Yun, Seok H.] Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. RP Yoon, YS (reprint author), Emory Univ, Sch Med, Dept Med, Div Cardiol, 1639 Pierce Dr,WMB 3009, Atlanta, GA 30332 USA. EM yyoon5@emory.edu RI Kim, Pilhan/C-1836-2011; Library, Woodruff Health/A-6096-2012; OI Kim, Pilhan/0000-0001-8388-1840; Kim, Hyongbum/0000-0002-4693-738X FU Department of Defense [W81XWH-09-1-0278]; National Institutes of Health [RO1HL084471, R21HL097353]; National Institutes of Health, National Center for Research Resources [UL1 RR025008]; Ministry of Science and Technology, Republic of Korea [SC4300] FX This work was supported in part by an Idea Grant Award from the Department of Defense (W81XWH-09-1-0278); National Institutes of Health grants (RO1HL084471, R21HL097353); a Public Health Services grant (UL1 RR025008) from the Clinical and Translational Science Award Program, National Institutes of Health, National Center for Research Resources; and a grant (SC4300) from the Stem Cell Research Center of the 21st Century Frontier Research Program funded by the Ministry of Science and Technology, Republic of Korea. NR 45 TC 32 Z9 32 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 5 PY 2010 VL 122 IS 14 BP 1413 EP + DI 10.1161/CIRCULATIONAHA.110.941468 PG 37 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 658RM UT WOS:000282507100015 PM 20855662 ER PT J AU Heist, EK Ruskin, JN AF Heist, E. Kevin Ruskin, Jeremy N. TI Drug-Induced Arrhythmia SO CIRCULATION LA English DT Review DE long QT syndrome; cardiac arrhythmias; drug therapy ID LONG-QT SYNDROME; TORSADE-DE-POINTES; SUDDEN CARDIAC DEATH; BRUGADA-SYNDROME; K+ CHANNEL; VENTRICULAR-FIBRILLATION; MACROLIDE ANTIBIOTICS; INTERVAL PROLONGATION; CLINICAL-FEATURES; SUPPRESSION TRIAL C1 [Ruskin, Jeremy N.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Heart, Boston, MA 02114 USA. RP Ruskin, JN (reprint author), Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, 55 Fruit St,GRB 109, Boston, MA 02114 USA. EM jruskin@partners.org FU Sanofi-Aventis; Astellas; AstraZeneca; Bristol Myers Squibb; Cardiome; Epix; Forest Labs; Genzyme; Javelin; Lundbeck; Millennium; Myriad; Novartis; NovoNordisk; Pfizer; Portola; Purdue; Sequel; Sunesis; Theravance FX Dr Heist reports receiving consulting fees from Sanofi-Aventis (consulting). Dr Ruskin reports receiving fees for advisory committees or consulting from Astellas, AstraZeneca, Bristol Myers Squibb, Cardiome, Epix, Forest Labs, Genzyme, Javelin, Lundbeck, Millennium, Myriad, Novartis, NovoNordisk, Pfizer, Portola, Purdue, Sanofi-Aventis, Sequel, Sunesis, and Theravance. NR 87 TC 35 Z9 40 U1 0 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 5 PY 2010 VL 122 IS 14 BP 1426 EP 1435 DI 10.1161/CIRCULATIONAHA.109.894725 PG 10 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 658RM UT WOS:000282507100016 PM 20921449 ER PT J AU Chung, KA Lobb, BM Nutt, JG Horak, FB AF Chung, Kathryn A. Lobb, Brenna M. Nutt, John G. Horak, Fay B. TI Effects of a central cholinesterase inhibitor on reducing falls in Parkinson disease SO NEUROLOGY LA English DT Article ID PEDUNCULOPONTINE TEGMENTAL NUCLEUS; NURSING-HOME RESIDENTS; BASALIS MAGNOCELLULARIS; POSTURAL CONTROL; DEMENTIA; RISK; ATTENTION; BALANCE; ANTIDEPRESSANTS; NEURONS AB Objective: To investigate if a central cholinesterase inhibitor will reduce falling frequency in subjects with Parkinson disease (PD) with advanced postural instability. Background: Falling due to postural instability is a significant problem in advancing PD, and is minimally impacted by dopaminergic therapy. Anticholinergic medications increase falling in the elderly. Further, CNS cholinergic neuron loss occurs in PD. We hypothesized that acetylcholine augmentation may reduce frequent falling in subjects with PD. Methods: We enrolled 23 subjects with PD who reported falling or nearly falling more than 2 times per week. In a randomized, placebo-controlled, crossover design, subjects were given 6 weeks of donepezil or placebo with a 3-week washout between phases. The primary outcomes were daily falls and near falls reported on postcards. Secondary outcomes included scores on the Activities of Balance Confidence Scale, Berg Balance Scale, Clinical Global Impression of Change, Folstein Mini-Mental State Examination, and the motor section of the Unified Parkinson's Disease Rating Scale. Results: Fall frequency per day on placebo was 0.25 +/- 0.08 (SEM) compared with 0.13 +/- 0.03 on donepezil (p < 0.05). The frequency of near falls was not significantly different between phases. The secondary outcomes did not differ; however, there was a trend to improvement on the subject-completed Global Impression of Change scale. Conclusions: Subjects with PD fell approximately half as often during the 6 weeks on donepezil than on placebo. Larger trials of cholinergic augmentation are warranted in subjects with PD with frequent falls. Classification of evidence: This study provides Class II evidence that donepezil (maximum 10 mg per day) significantly reduced the number of falls in patients with PD (0.13 falls/day, SEM = 0.03) than when taking placebo (0.25 falls/day, SEM = 0.08, p = 0.049). Neurology (R) 2010;75:1263-1269 C1 [Chung, Kathryn A.; Nutt, John G.; Horak, Fay B.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA. [Lobb, Brenna M.] Portland VA Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, Portland, OR USA. RP Chung, KA (reprint author), OP 32,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM chungka@ohsu.edu FU Veterans Administration; US Public Health Service [ULIRR024140-02]; NIH [R01-NS21062, NIA AG006457, NINDS R01 NS 21062, UL1-RR024140, NIDCD R01 DC004082-07, NIA R37 AG006457, RC1 NS068678]; Pfizer Inc.; Department of Veterans Affairs; Novartis; Teva Pharmaceutical Industries Ltd.; Schering-Plough Corp; National Parkinson Foundation; National MS Society; Parkinson's Alliance; Kinetics Foundation FX This was an investigator-initiated project funded with an unrestricted grant from Pfizer Inc., who did not design or monitor the study or receive the data or influence the writing of the manuscript. Supported by a Veterans Administration Career Development Award, US Public Health Service Grant (ULIRR024140-02), and the NIH (R01-NS21062 and NIA AG006457). Pfizer Inc. provided drug and matched placebo.; Dr. Chung has received research support from a VA Career Development Award. B. M. Lobb receives support from the Department of Veterans Affairs. Dr. Nutt has received funding for travel from Novartis and Teva Pharmaceutical Industries Ltd.; has received speaker honoraria from Novartis; has served as a consultant for XenoPort Inc., IMPAX Laboratories, Inc., Neurogen Inc., Synosia Therapeutics, and NeuroDerm, Ltd.; and has received research support from Schering-Plough Corp, the NIH (NINDS R01 NS 21062 [PI] and UL1-RR024140 [PI]), the Veterans Administration (PADRECC [Co-PI]), and the National Parkinson Foundation. Dr. Horak serves on scientific advisory boards for the Movement Disorders Society, Novartis, and the MS Society; serves as an Associate Editor for Cerebellum and on the editorial boards of Gait and Posture and the Journal of Biomechanics; holds/has filed patents re: Device for conditioning balance and motor coordination and instrumented mobility system to objectively measure balance and gait; serves as Chief Scientific Officer and member of the board of APDM, Inc.; and receives research support from the NIH (NIDCD R01 DC004082-07 [PI], NIA R37 AG006457 [PI], and RC1 NS068678 [PI]), the National MS Society, Parkinson's Alliance, and the Kinetics Foundation. NR 39 TC 89 Z9 92 U1 2 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD OCT 5 PY 2010 VL 75 IS 14 BP 1263 EP 1269 DI 10.1212/WNL.0b013e3181f6128c PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 663JW UT WOS:000282883900011 PM 20810998 ER PT J AU Arsava, EM Ballabio, E Benner, T Cole, JW Delgado-Martinez, MP Dichgans, M Fazekas, F Furie, KL Illoh, K Jood, K Kittner, S Lindgren, AG Majersik, JJ Macleod, MJ Meurer, WJ Montaner, J Olugbodi, AA Pasdar, A Redfors, P Schmidt, R Sharma, P Singhal, AB Sorensen, AG Sudlow, C Thijs, V Worrall, BB Rosand, J Ay, H AF Arsava, E. M. Ballabio, E. Benner, T. Cole, J. W. Delgado-Martinez, M. P. Dichgans, M. Fazekas, F. Furie, K. L. Illoh, K. Jood, K. Kittner, S. Lindgren, A. G. Majersik, J. J. Macleod, M. J. Meurer, W. J. Montaner, J. Olugbodi, A. A. Pasdar, A. Redfors, P. Schmidt, R. Sharma, P. Singhal, A. B. Sorensen, A. G. Sudlow, C. Thijs, V. Worrall, B. B. Rosand, J. Ay, H. CA Int Stroke Genetics Consortium TI The Causative Classification of Stroke system An international reliability and optimization study SO NEUROLOGY LA English DT Article ID MODIFIED RANKIN SCALE; ACUTE ISCHEMIC-STROKE; CLINICAL-TRIALS AB Background: Valid and reliable ischemic stroke subtype determination is crucial for well-powered multicenter studies. The Causative Classification of Stroke System (CCS, available at http://ccs.mgh.harvard.edu) is a computerized, evidence-based algorithm that provides both causative and phenotypic stroke subtypes in a rule-based manner. We determined whether CCS demonstrates high interrater reliability in order to be useful for international multicenter studies. Methods: Twenty members of the International Stroke Genetics Consortium from 13 centers in 8 countries, who were not involved in the design and development of the CCS, independently assessed the same 50 consecutive patients with acute ischemic stroke through reviews of abstracted case summaries. Agreement among ratings was measured by kappa statistic. Results: The kappa value for causative classification was 0.80 (95% confidence interval [ CI] 0.78-0.81) for the 5-subtype, 0.79 (95% CI 0.77-0.80) for the 8-subtype, and 0.70 (95% CI 0.69-0.71) for the 16-subtype CCS. Correction of a software-related factor that generated ambiguity improved agreement: kappa = 0.81 (95% CI 0.79-0.82) for the 5-subtype, 0.79 (95% CI 0.77-0.80) for the 8-subtype, and 0.79 (95% CI 0.78-0.80) for the 16-subtype CCS. The kappa value for phenotypic classification was 0.79 (95% CI 0.77-0.82) for supra-aortic large artery atherosclerosis, 0.95 (95% CI 0.93-0.98) for cardioembolism, 0.88 (95% CI 0.85-0.91) for small artery occlusion, and 0.79 (0.76-0.82) for other uncommon causes. Conclusions: CCS allows classification of stroke subtypes by multiple investigators with high reliability, supporting its potential for improving stroke classification in multicenter studies and ensuring accurate means of communication among different researchers, institutions, and eras. Neurology (R) 2010;75:1277-1284 C1 [Arsava, E. M.; Benner, T.; Sorensen, A. G.; Ay, H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, AA Martinos Ctr Biomed Imaging,Dept Radiol, Charlestown, MA 02129 USA. [Furie, K. L.; Singhal, A. B.; Rosand, J.; Ay, H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol,Stroke Serv, Charlestown, MA 02129 USA. [Rosand, J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Charlestown, MA 02129 USA. [Ballabio, E.] Natl Neurol Inst, Milan, Italy. [Cole, J. W.; Kittner, S.] Univ Maryland, Baltimore, MD 21201 USA. [Cole, J. W.; Kittner, S.] Dept Vet Affairs Med Ctr, Baltimore, MD USA. [Delgado-Martinez, M. P.; Montaner, J.] Vall dHebron Hosp, Neurovasc Res Lab, Dept Neurol, Barcelona, Spain. [Dichgans, M.] Univ Munich, Inst Stroke & Dementia Res, Munich, Germany. [Dichgans, M.] Univ Munich, Neurol Klin, Munich, Germany. [Fazekas, F.; Schmidt, R.] Med Univ Graz, Dept Neurol, Graz, Austria. [Illoh, K.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Gothenburg, Sweden. [Jood, K.; Redfors, P.] Sahlgrens Univ Hosp, Dept Neurol, Gothenburg, Sweden. [Lindgren, A. G.] Univ Lund Hosp, Dept Neurol, S-22185 Lund, Sweden. [Majersik, J. J.] Univ Utah, Stroke Ctr, Salt Lake City, UT USA. [Pasdar, A.] Univ Aberdeen, Dept Mental Hlth, Aberdeen, Scotland. [Macleod, M. J.] Univ Aberdeen, Div Appl Med, Aberdeen, Scotland. [Meurer, W. J.] Univ Michigan, Dept Emergency Med, Ann Arbor, MI USA. [Meurer, W. J.] Univ Michigan, Dept Neurol, Ann Arbor, MI USA. [Olugbodi, A. A.] Obafemi Awolowo Univ, Coll Hlth Sci, Dept Med, Ife, Osun State, Nigeria. [Sharma, P.] Hammersmith Hosp, Dept Clin Neurosci, London, England. [Sharma, P.] Univ London Imperial Coll Sci Technol & Med, London, England. [Sudlow, C.] Univ Edinburgh, Div Clin Neurosci, Edinburgh, Midlothian, Scotland. [Sudlow, C.] Univ Edinburgh, Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland. [Thijs, V.] Katholieke Univ Leuven Hosp, Dept Neurol, Louvain, Belgium. [Worrall, B. B.] Univ Virginia, Ctr Publ Hlth Genom, Dept Publ Hlth Sci, Charlottesville, VA USA. Univ Virginia, Dept Neurol, Charlottesville, VA USA. [Rosand, J.] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA. RP Ay, H (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, AA Martinos Ctr Biomed Imaging,Dept Radiol, 13th St,Bldg 149,Room 2301, Charlestown, MA 02129 USA. EM hay@partners.org RI Thijs, Vincent/C-3647-2009; Arsava, Ethem Murat/I-9197-2013; OI Thijs, Vincent/0000-0002-6614-8417; Arsava, Ethem Murat/0000-0002-6527-4139; Macleod, Mary Joan/0000-0003-2115-8184 FU US Department of Veterans Affairs; NIH [NINDS R01 NS045012-05, NINDS 1RO1NS045012-01A1, 1U01NS069208, NHGI 1U01HG004436-01A1, NINDS P50NS044283, NINDS NS38477, NCI CA137254, NINDS NS063925, NINDS NS061119, NHGRI/NIH U-01 HG005160, U01 NS069208-01, NINDS R25 NS065733, NINDS R01 NS42147]; BMB; NGFN-Plus; Wellcome Trust; Foundation for Vascular Dementia Research; Bayer Schering Pharma; Bayer Vital GmbH; Baxter International Inc.; Biogen Idec; Merck Serono; Teva Pharmaceutical Industries Ltd./Sanofi-Aventis; NIH/NINDS [R01-HS011392, P50-NS051343, P50 NS051343, R01NS051412, P01 NS035611, R01NS059775-01, R01NS38477]; American Heart Association; Deane Institute; Yngve Land foundation for neurological research; Swedish Research Council; Lund University; Region Skane; Strokeriksforbundet; Emergency Medicine Foundation; Pfizer Inc.; Novartis; Merz Pharmaceuticals; LLC; Lundbeck Inc.; Takeda Pharmaceutical Company Limited; UK Department of Health; Genentech, Inc.; Siemens Medical Solutions; Millennium Pharmaceuticals, Inc.; AstraZeneca; Genentech Inc.; Schering Plough Corp; Scottish Executive Health Department; UK Binks Trust; Boehringer Ingelheim; Shire plc; SERVIER; Schering-Plough Corp; SYGNIS AG; CoAxia, Inc.; Medtronic, Inc.; Novo Nordisk; Bristol-Myers Squibb; ThromboGenics NV; Eli Lilly and Company; Sanofi- Aventis; Daiichi Sankyo; Asubio Pharmaceuticals, Inc.; FWO Flanders; Vlaams Instituut voor Biotechnologie; University of Virginia-CTSA; Deane Institute for Integrative Research in Atrial Fibrillation and Stroke FX Dr. Arsava and Dr. Ballabio report no disclosures. Dr. Benner serves/has served as a consultant for Siemens Medical Solutions, Bayer Schering Pharma, and Perceptive Informatics. Dr. Cole receives royalties from the publication of Stroke Essentials for Primary Care (Springer, 2009); received a speaker honorarium from Concentric Medical Inc.; serves as a consultant for Wyeth; and receives research support from the US Department of Veterans Affairs and the NIH (NINDS R01 NS045012-05 [Co-I]). Dr. Delgado-Martinez reports no disclosures. Dr. Dichgans served as Genetics Section Editor for Stroke and receives research support from BMB, NGFN-Plus, Wellcome Trust, and the Foundation for Vascular Dementia Research. Dr. Fazekas serves on scientific advisory boards for Biogen Idec and Teva Pharmaceutical Industries Ltd./Sanofi-Aventis; serves on the editorial advisory boards of Cerebrovascular Diseases, the Polish Journal of Neurology and Neurosurgery, the Journal of Neurology, Stroke, and the Swiss Archives of Neurology and Psychiatry; and has received consulting fees, speaker honoraria, and grant support from Bayer Schering Pharma, Bayer Vital GmbH, Baxter International Inc., Biogen Idec, Merck Serono, and Teva Pharmaceutical Industries Ltd./Sanofi-Aventis. Dr. Furie has served on scientific advisory boards for Novartis and GE Healthcare and receives research support from the NIH/NINDS [R01-HS011392 (PI) and P50-NS051343 (PI)], the American Heart Association, and the Deane Institute. Dr. Illoh reports no disclosures. Dr. Jood has received research support from the Yngve Land foundation for neurological research. Dr. Kittner receives research support from the NIH (NINDS 1RO1NS045012-01A1 [PI], NINDS 1U01NS069208 [Co-PI], and NHGI 1U01HG004436-01A1 [Co-I]) and the US Department of Veterans Affairs; and has provided expert witness testimony in medico-legal cases. Dr. Lindgren serves on scientific advisory boards for Boehringer Ingelheim and Sanofi-Aventis/Bristol-Myers Squibb; has received speaker honoraria from AstraZeneca; and receives research support from the Swedish Research Council, Lund University, Region Skane, and Strokeriksforbundet. Dr. Majersik and Dr. Macleod report no disclosures. Dr. Meurer receives research support from the NIH (NINDS P50NS044283 [Site PI]) and the Emergency Medicine Foundation. Dr. Montaner, Dr. Olugbodi, Dr. Pasdar, and Dr. Redfors report no disclosures. Dr. Schmidt serves on a scientific advisory board for Novartis; has received funding for travel and speaker honoraria from Pfizer Inc., Novartis, Merz Pharmaceuticals, LLC, Lundbeck Inc., and Takeda Pharmaceutical Company Limited; and serves on the editorial boards of Clinical Neurology and Neurosurgery and Neuropsychiatrie. Dr. Sharma has served on a scientific advisory board for Boehringer Ingelheim; has received speaker honoraria from Sanofi-Aventis and Bristol-Myers Squibb; and receives fellowship support from the UK Department of Health. Dr. Singhal has received research support from the NIH/NINDS (P50 NS051343 [Project PI], R01NS051412 [PI], P01 NS035611 [Co-I], R01NS059775-01 [Co-I], and R01NS38477 [Co-I]); his wife is an employee of and holds stock options in Vertex Pharmaceuticals; and has served as a medical expert witness in medicolegal cases concerning stroke. Dr. Sorensen has served on scientific advisory boards for Olea Medical and Breakaway Imaging; has received funding for travel from Genentech, Inc., Siemens Medical Solutions, Millennium Pharmaceuticals, Inc.; , and AstraZeneca; serves as a Section Editor of Stroke and on the editorial boards of Th Oncologist and the Journal of Clinical Oncology; holds patents re: Method for evaluating novel, stroke treatments using a tissue risk map, Imaging system for obtaining quantitative perfusion indices, Delay-compensated calculation of tissue blood flow, High-flow oxygen delivery system and methods of use thereof, and Magnetic resonance spatial risk map for tissue outcome prediction; receives royalties from the publication of Cerebral MR Perfusion Imaging (Thieme, 2000); has received speaker honoraria from Siemens Medical Solutions, Novartis, and GE Healthcare; has served as a consultant to Mitsubishi Tanabe Pharma Corporation, AstraZeneca, and Genentech, Inc.; receives research support from Millennium Pharmaceuticals, Inc., Siemens Medical Solutions, AstraZeneca, Genentech Inc., Novartis, Merck Serono, Schering Plough Corp, and the NIH [NINDS NS38477 (PI), NCI CA137254 (PI), NINDS NS063925 (PI), and NINDS NS061119 (PI)]; and holds stock and stock options in Epix Pharmaceuticals. Dr. Sudlow serves/has served on the editorial boards of Stroke, BioMed Central Cardiovascular Disorders, the British Medical Journal, and the Cochrane Stroke Group; receives royalties from the publication of Stroke: A Practical Guide to Management, 3rd ed. (Blackwell, 2008); and receives research support from the Scottish Executive Health Department, the Wellcome Trust, and the UK Binks Trust Research Fellowship. Dr. Thijs serves/has served on scientific advisory boards for Shire plc, Merck Serono, and SYGNIS AG; had received funding for travel from Boehringer Ingelheim and Shire plc; served as an Associate Editor for Acta Neurologica Belgica; has received speaker honoraria from Shire plc, Abbott, Pfizer Inc., Boehringer Ingelheim, and Medtronic, Inc.; receives research support from SERVIER, Schering-Plough Corp., SYGNIS AG, CoAxia, Inc., Medtronic, Inc., Novo Nordisk, Bristol-Myers Squibb, Pfizer Inc., Shire plc, AstraZeneca, ThromboGenics NV, Eli Lilly and Company, Sanofi- Aventis, Boehringer Ingelheim, Daiichi Sankyo, Asubio Pharmaceuticals, Inc., FWO Flanders, and Vlaams Instituut voor Biotechnologie; and holds stock in Novo Nordisk. Dr. Worrall serves as an Associate Editor of Neurology (R) and on the editorial board of Seminars in Neurology; receives royalties from the publication of Merritt's Neurology, 10th, 11th, and 12th ed. (chapter author); receives/has received research support from the NIH (NHGRI/NIH U-01 HG005160 [Co-PI], U01 NS069208-01[Co-PI], NHLBI contract [PI], NINDS R25 NS065733 [Mentor], NINDS R01 NS42147 [Site PI], NINDS R01 NS 39987 [Executive committee, Site PI], NINDS R01 NS039512 [Executive committee, Co-I], NHLBI contract [Physician investigator], K08-NS45802 [PI], and R01-NS42733 [Site PI]), and the University of Virginia-CTSA Pilot Project. Dr. Rosand serves on the editorial board of Stroke and receives research support from the NIH (5R01NS059727-02 [PI], 3RO1NS059727-01A1S1 [PI], and U01 NS069208-01 [Site PI]), the American Heart Association, and the Deane Institute for Integrative Research in Atrial Fibrillation and Stroke. Dr. Ay receives research support from the NIH (R01-NS059710 [PI] and U01 NS069208-01. NR 20 TC 28 Z9 28 U1 2 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 OCT 5 PY 2010 VL 75 IS 14 BP 1277 EP 1284 DI 10.1212/WNL.0b013e3181f612ce PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 663JW UT WOS:000282883900013 PM 20921513 ER PT J AU Ji, GX Gu, AH Zhou, Y Shi, XG Xia, YK Long, Y Song, L Wang, SL Wang, XR AF Ji, Guixiang Gu, Aihua Zhou, Yong Shi, Xiangguo Xia, Yankai Long, Yan Song, Ling Wang, Shoulin Wang, Xinru TI Interactions between Exposure to Environmental Polycyclic Aromatic Hydrocarbons and DNA Repair Gene Polymorphisms on Bulky DNA Adducts in Human Sperm SO PLOS ONE LA English DT Article ID URINARY METABOLITES; MALE-INFERTILITY; EXCISION-REPAIR; BREAST-CANCER; SEMEN QUALITY; LUNG-CANCER; DAMAGE; SMOKING; XRCC1; RISK AB Background: Nucleotide excision repair (NER) and base excision repair (BER) are the primary mechanisms for repair of bulky adducts caused by chemical agents, such as PAHs. It is expected that polymorphisms in NER or BER genes may modulate individual susceptibility to PAHs exposure. Here, we evaluate the effects of PAHs exposure and polymorphisms in NER and BER pathway, alone or combined, on polycyclic aromatic hydrocarbon-DNA (PAH-DNA) adducts in human sperm. Methodology/Principal Findings: Sperm PAH-DNA adducts were measured by immunofluorescent assay using flow cytometry in a sample of 465 infertile adults. Polymorphisms of XPA, XPD, ERCC1, XPF, and XRCC1 were determined by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) techniques. The PAHs exposure was detected as urinary 1-hydroxypyrene (1-OHP) levels. In multivariate models adjusted for potential confounders, we observed that XRCC1 5'pUTR -T/C, Arg194Trp, Arg399Gln polymorphisms were associated with increased sperm adduct levels. Furthermore, the stratified analysis indicated that adverse effects of XRCC1 Arg194Trp, Arg399Gln polymorphisms on PAH-DNA adducts were detected only in the high PAHs exposure group. Conclusions/Significance: These findings provided the first evidence that polymorphisms of XRCC1 may modify sperm PAH-DNA adduct levels and may be useful biomarkers to identify individuals susceptible to DNA damage resulting from PAHs exposure. C1 [Ji, Guixiang; Gu, Aihua; Shi, Xiangguo; Xia, Yankai; Long, Yan; Song, Ling; Wang, Shoulin; Wang, Xinru] Nanjing Med Univ, Inst Toxicol, Sch Publ Hlth, Key Lab Reprod Med, Nanjing, Peoples R China. [Zhou, Yong] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Ji, GX (reprint author), Nanjing Med Univ, Inst Toxicol, Sch Publ Hlth, Key Lab Reprod Med, Nanjing, Peoples R China. EM xrwang@njmu.edu.cn FU National Basic Research Program of China [2009CB941703]; Key Project of National Natural Science Foundation of China [30930079]; National Science Foundation of China [30901210, 30800927] FX This study was supported in part by National Basic Research Program of China (973 Program, 2009CB941703); The Key Project of National Natural Science Foundation of China (30930079); The National Science Foundation of China (No. 30901210; No. 30800927). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 38 TC 7 Z9 10 U1 2 U2 15 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD OCT 5 PY 2010 VL 5 IS 10 AR e13145 DI 10.1371/journal.pone.0013145 PG 8 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 658RC UT WOS:000282506100003 ER PT J AU Doores, KJ Fulton, Z Hong, V Patel, MK Scanlan, CN Wormald, MR Finn, MG Burton, DR Wilson, IA Davis, BG AF Doores, Katie J. Fulton, Zara Hong, Vu Patel, Mitul K. Scanlan, Christopher N. Wormald, Mark R. Finn, M. G. Burton, Dennis R. Wilson, Ian A. Davis, Benjamin G. TI A nonself sugar mimic of the HIV glycan shield shows enhanced antigenicity SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE 2G12; gp120; oligosaccharide; glycoconjugate; glycomimetic ID IMMUNODEFICIENCY-VIRUS TYPE-1; NEUTRALIZING ANTIBODY 2G12; VACCINE DESIGN; CRYSTAL-STRUCTURE; HUMAN-IGG; EPITOPE; GP120; GLYCOPROTEIN; RECOGNITION; TEMPLATE AB Antibody 2G12 uniquely neutralizes a broad range of HIV-1 isolates by binding the high-mannose glycans on the HIV-1 surface glycoprotein, gp120. Antigens that resemble these natural epitopes of 2G12 would be highly desirable components for an HIV-1 vaccine. However, host-produced (self)-carbohydrate motifs have been unsuccessful so far at eliciting 2G12-like antibodies that cross-react with gp120. Based on the surprising observation that 2G12 binds nonproteinaceous monosaccharide D-fructose with higher affinity than D-mannose, we show here that a designed set of nonself, synthetic monosaccharides are potent antigens. When introduced to the terminus of the D1 arm of protein glycans recognized by 2G12, their antigenicity is significantly enhanced. Logical variation of these unnatural sugars pinpointed key modifications, and the molecular basis of this increased antigenicity was elucidated using high-resolution crystallographic analyses. Virus-like particle protein conjugates containing such nonself glycans are bound more tightly by 2G12. As immunogens they elicit higher titers of antibodies than those immunogenic conjugates containing the self D1 glycan motif. These antibodies generated from nonself immunogens also cross-react with this self motif, which is found in the glycan shield, when it is presented in a range of different conjugates and glycans. However, these antibodies did not bind this glycan motif when present on gp120. C1 [Fulton, Zara; Wilson, Ian A.] Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA. [Doores, Katie J.; Patel, Mitul K.; Davis, Benjamin G.] Univ Oxford, Chem Res Lab, Dept Chem, Oxford OX1 3TA, England. [Doores, Katie J.; Burton, Dennis R.] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA. [Hong, Vu; Finn, M. G.] Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA. [Hong, Vu; Finn, M. G.; Wilson, Ian A.] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA. [Doores, Katie J.; Burton, Dennis R.] Scripps Res Inst, Int AIDS Vaccine Initiat Neutralising Antibody Ct, La Jolla, CA 92037 USA. [Scanlan, Christopher N.; Wormald, Mark R.] Univ Oxford, Dept Biochem, Glycobiol Inst, Oxford OX1 3QU, England. [Doores, Katie J.; Burton, Dennis R.] MIT, Ragon Inst, Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Wilson, IA (reprint author), Scripps Res Inst, Dept Mol Biol, 10550 N Torrey Pines Rd, La Jolla, CA 92037 USA. EM wilson@scripps.edu; ben.davis@chem.ox.ac.uk RI Wormald, Mark/G-2785-2011; Davis, Benjamin/C-5281-2011; OI Wormald, Mark/0000-0002-4853-2773; Davis, Benjamin/0000-0002-5056-407X; Doores, Katie/0000-0002-5507-1725 FU National Institutes of Health [GM46192, AI84817]; Phillip Leverhulme Prize in Molecular Biology; Neutralizing Antibody Consortium of the International AIDS Vaccine Initiative; Skaggs Institute for Chemical Biology; Royal Society; Engineering and Physical Sciences Research Council FX We thank the staffs of the Advanced Light Source and Advanced Photon Source, and Sander van Kasteren for technical assistance. This work was supported by National Institutes of Health Grants GM46192 and AI84817 (to I. A. W.) and funds from the Phillip Leverhulme Prize in Molecular Biology (B. G. D.), the Neutralizing Antibody Consortium of the International AIDS Vaccine Initiative, and the Skaggs Institute for Chemical Biology. B. G. D. is a Royal Society-Wolfson Research Merit Award recipient and supported by an Engineering and Physical Sciences Research Council Life Sciences Interface Platform Grant. NR 39 TC 54 Z9 54 U1 1 U2 28 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 5 PY 2010 VL 107 IS 40 BP 17107 EP 17112 DI 10.1073/pnas.1002717107 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 658TJ UT WOS:000282512000013 PM 20852065 ER PT J AU Stern, JNH Keskin, DB Kato, Z Waldner, H Schallenberg, S Anderson, A von Boehmerd, H Kretschmer, K Strominger, JL AF Stern, Joel N. H. Keskin, Derin B. Kato, Zenichiro Waldner, Hanspeter Schallenberg, Sonja Anderson, Ana von Boehmerd, Harald Kretschmer, Karsten Strominger, Jack L. TI Promoting tolerance to proteolipid protein-induced experimental autoimmune encephalomyelitis through targeting dendritic cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE DEC205; multiple sclerosis; anergy; monophosphoryl lipid A; T cells ID REGULATORY T-CELLS; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; ANTIGEN-PRESENTING CELLS; IN-VIVO; SJL MICE; DISEASE; SELF; UNRESPONSIVENESS; INDUCTION; RECEPTOR AB In T cell-mediated autoimmune diseases, self-reactive T cells with known antigen specificity appear to be particularly promising targets for antigen-specific induction of tolerance without compromising desired protective host immune responses. Several lines of evidence suggest that delivery of antigens to antigen-presenting dendritic cells (DCs) in the steady state (i.e., to immature DCs) may represent a suitable approach to induce antigen-specific T-cell tolerance peripherally. Here, we report that anti-DEC205-mediated delivery of the self-peptide proteolipid protein (PLP) 139-151 to DCs ameliorated clinical symptoms in the PLP-induced SJL model of experimental autoimmune encephalomyelitis. Splenocytes from treated mice were anergized to PLP139-151, and IL-17 secretion was markedly reduced. Moreover, we show directly, using transgenic CD4(+) V beta 6(+) TCR T cells specific for PLP139-151, that, under the conditions of the present experiments, these cells also became anergic. In addition, evidence for a CD4(+) T cell-mediated suppressor mechanism was obtained. C1 [Stern, Joel N. H.; Keskin, Derin B.; Kato, Zenichiro; Strominger, Jack L.] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. [Waldner, Hanspeter; Anderson, Ana] Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA. [Schallenberg, Sonja; Kretschmer, Karsten] Tech Univ Dresden, Ctr Regenerat Therapies Dresden, D-01307 Dresden, Germany. [von Boehmerd, Harald; Kretschmer, Karsten] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. [von Boehmerd, Harald] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. RP Stern, JNH (reprint author), Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. EM jstern@fas.harvard.edu; karsten.krestschmer@crt-dresden.de; jlstrom@fas.harvard.edu RI Kretschmer, Karsten/E-8174-2010; Schallenberg, Sonja/F-6220-2012; OI Stern, Joel N.H./0000-0002-1259-2256 FU National Institute of Allergy and Infectious Diseases [AI049524]; National Multiple Sclerosis Society [RG 3796A3/1] FX We thank M. Nussenzweig (The Rockefeller University, New York) for providing the plasmid vectors of the IgH and respective Ig kappa light chain cDNA of cloned anti-DEC205 NLDC-145 and III/10 isotype control recombinant antibodies and T. Koenig (Kretschmer Laboratory) for excellent technical assistance in recombinant antibody production. This work was supported by grants from the National Institute of Allergy and Infectious Diseases (AI049524) and from the National Multiple Sclerosis Society (RG 3796A3/1). NR 35 TC 34 Z9 35 U1 0 U2 5 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 5 PY 2010 VL 107 IS 40 BP 17280 EP 17285 DI 10.1073/pnas.1010263107 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 658TJ UT WOS:000282512000043 PM 20855626 ER PT J AU North, TE Babu, IR Vedder, LM Lord, AM Wishnok, JS Tannenbaum, SR Zon, LI Goessling, W AF North, Trista E. Babu, I. Ramesh Vedder, Lea M. Lord, Allegra M. Wishnok, John S. Tannenbaum, Steven R. Zon, Leonard I. Goessling, Wolfram TI PGE2-regulated wnt signaling and N-acetylcysteine are synergistically hepatoprotective in zebrafish acetaminophen injury SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE acetaminophen liver toxicity; chemical screen ID INDUCED HEPATIC NECROSIS; LIVER-REGENERATION; DANIO-RERIO; HEPATOTOXICITY; PROTEOME; MICE; PARACETAMOL; GLUTATHIONE; BIOMARKERS; INHIBITOR AB Acetaminophen (APAP) toxicity is the most common drug-induced cause of acute liver failure in the United States. The only available treatment, N-acetylcysteine (NAC), has a limited time window of efficacy, indicating a need for additional therapeutic options. Zebrafish have emerged as a powerful tool for drug discovery. Here, we developed a clinically relevant zebrafish model of APAP toxicity. APAP depleted glutathione stores, elevated aminotransferase levels, increased apoptosis, and caused dose-dependent hepatocyte necrosis. These outcomes were limited by NAC and conserved in zebrafish embryos. In a targeted embryonic chemical screen, prostaglandin E2 (PGE2) was identified as a potential therapeutic agent; in the adult, PGE2 similarly decreased APAP-associated toxicity. Significantly, when combined with NAC, PGE2 extended the time window for a successful intervention, synergistically reducing apoptosis, improving liver enzymes, and preventing death. Use of a wnt reporter zebrafish line and chemical genetic epistasis showed that the effects of PGE2 are mediated through the wnt signaling pathway. Zebrafish can be used as a clinically relevant toxicological model amenable to the identification of additional therapeutics and biomarkers of APAP injury; our data suggest combinatorial PGE2 and NAC treatment would be beneficial for patients with APAP-induced liver damage. C1 [North, Trista E.; Lord, Allegra M.; Zon, Leonard I.; Goessling, Wolfram] MIT, Dept Biol Engn, Cambridge, MA 02139 USA. [North, Trista E.; Vedder, Lea M.] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02115 USA. [Babu, I. Ramesh; Wishnok, John S.; Tannenbaum, Steven R.] MIT, Dept Biol Engn, Cambridge, MA 02139 USA. [North, Trista E.; Zon, Leonard I.; Goessling, Wolfram] Harvard Stem Cell Inst, Cambridge, MA 02138 USA. [Lord, Allegra M.; Zon, Leonard I.] Childrens Hosp, Stem Cell Program, Boston, MA 02115 USA. [Tannenbaum, Steven R.] MIT, Dept Chem, Cambridge, MA 02139 USA. [Zon, Leonard I.] Howard Hughes Med Inst, Boston, MA 02115 USA. [Goessling, Wolfram] Brigham & Womens Hosp, Div Genet, Gastrointestinal Canc Ctr, Dana Farber Canc Inst, Boston, MA 02115 USA. [Goessling, Wolfram] Brigham & Womens Hosp, Div Gastroenterol, Gastrointestinal Canc Ctr, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Goessling, W (reprint author), MIT, Dept Biol Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA. EM wgoessling@partners.org OI Goessling, Wolfram/0000-0001-9972-1569 FU Dana-Farber fellowship; Harvard Digestive Diseases Center; Mount Desert Island Biological Laboratory; American Cancer Society; Harvard Stem Cell Institute; National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases; National Cancer Institute [CA26731]; Massachusetts Institute of Technology Center for Environmental Health Sciences; Howard Hughes Medical Institute FX This research was supported by a Friends of Dana-Farber fellowship (to W.G.), Harvard Digestive Diseases Center (W.G.), a Mount Desert Island Biological Laboratory Junior Investigator Award (to W.G.), American Cancer Society (T.E.N.), Harvard Stem Cell Institute (T.E.N. and W.G.), National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases (T.E.N., L.I.Z., and W.G), National Cancer Institute (I.R.B. and S.R.T., CA26731), Massachusetts Institute of Technology Center for Environmental Health Sciences (J.S.W.), and Howard Hughes Medical Institute (L.I.Z.). NR 36 TC 50 Z9 52 U1 1 U2 18 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 5 PY 2010 VL 107 IS 40 BP 17315 EP 17320 DI 10.1073/pnas.1008209107 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 658TJ UT WOS:000282512000049 PM 20855591 ER PT J AU Canolty, RT Ganguly, K Kennerley, SW Cadieu, CF Koepsell, K Wallis, JD Carmena, JM AF Canolty, Ryan T. Ganguly, Karunesh Kennerley, Steven W. Cadieu, Charles F. Koepsell, Kilian Wallis, Jonathan D. Carmena, Jose M. TI Oscillatory phase coupling coordinates anatomically dispersed functional cell assemblies SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE neuronal oscillations; neuronal ensembles; spike timing; local field potentials; brain rhythms ID NEURONAL OSCILLATIONS; NEOCORTICAL NEURONS; THETA-OSCILLATIONS; AUDITORY-CORTEX; MOTOR CORTEX; BEHAVING RAT; IN-VITRO; GAMMA; NETWORK; SYNCHRONIZATION AB Hebb proposed that neuronal cell assemblies are critical for effective perception, cognition, and action. However, evidence for brain mechanisms that coordinate multiple coactive assemblies remains lacking. Neuronal oscillations have been suggested as one possible mechanism for cell assembly coordination. Prior studies have shown that spike timing depends upon local field potential (LFP) phase proximal to the cell body, but few studies have examined the dependence of spiking on distal LFP phases in other brain areas far from the neuron or the influence of LFP-LFP phase coupling between distal areas on spiking. We investigated these interactions by recording LFPs and single-unit activity using multiple microelectrode arrays in several brain areas and then used a unique probabilistic multivariate phase distribution to model the dependence of spike timing on the full pattern of proximal LFP phases, distal LFP phases, and LFP-LFP phase coupling between electrodes. Here we show that spiking activity in single neurons and neuronal ensembles depends on dynamic patterns of oscillatory phase coupling between multiple brain areas, in addition to the effects of proximal LFP phase. Neurons that prefer similar patterns of phase coupling exhibit similar changes in spike rates, whereas neurons with different preferences show divergent responses, providing a basic mechanism to bind different neurons together into coordinated cell assemblies. Surprisingly, phase-coupling-based rate correlations are independent of interneuron distance. Phase-coupling preferences correlate with behavior and neural function and remain stable over multiple days. These findings suggest that neuronal oscillations enable selective and dynamic control of distributed functional cell assemblies. C1 [Canolty, Ryan T.; Ganguly, Karunesh; Kennerley, Steven W.; Cadieu, Charles F.; Koepsell, Kilian; Wallis, Jonathan D.; Carmena, Jose M.] Univ Calif Berkeley, Helen Wills Neurosci Inst, Berkeley, CA 94720 USA. [Ganguly, Karunesh] San Francisco VA Med Ctr, San Francisco, CA 94121 USA. [Ganguly, Karunesh] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Cadieu, Charles F.; Koepsell, Kilian] Univ Calif Berkeley, Redwood Ctr Theoret Neurosci, Berkeley, CA 94720 USA. [Wallis, Jonathan D.] Univ Calif Berkeley, Dept Psychol, Berkeley, CA 94720 USA. [Carmena, Jose M.] Univ Calif Berkeley, Program Cognit Sci, Berkeley, CA 94720 USA. RP Carmena, JM (reprint author), Univ Calif Berkeley, Helen Wills Neurosci Inst, Berkeley, CA 94720 USA. EM carmena@eecs.berkeley.edu OI Wallis, Joni/0000-0001-7262-7417 FU National Institutes of Health [R01DA-19028, P01NS-040813, F32MH-081521]; National Science Foundation [IIS-0941343, IIS-0917342, IIS-1010239]; US Department of Veterans Affairs and American Heart Association; Defense Advanced Research Projects Agency [N66001-10-C-2008]; Multiscale Systems Center FX This work was funded by National Institutes of Health Grants R01DA-19028 and P01NS-040813 (to J.D.W.), National Institutes of Health Grant F32MH-081521 (to S.W.K.), National Science Foundation Grants IIS-0941343 (to J.M.C.), IIS-0917342 (to K.K.) and IIS-1010239 (to C.F.C. and K.K.), the US Department of Veterans Affairs and American Heart Association (to K.G.), the Defense Advanced Research Projects Agency Contract N66001-10-C-2008, and the Multiscale Systems Center (to J.M.C.). NR 48 TC 114 Z9 115 U1 0 U2 17 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD OCT 5 PY 2010 VL 107 IS 40 BP 17356 EP 17361 DI 10.1073/pnas.1008306107 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 658TJ UT WOS:000282512000056 PM 20855620 ER PT J AU Xu, Y Sun, YL Jiang, XF Ayrapetov, MK Moskwa, P Yang, SH Weinstock, DM Price, BD AF Xu, Ye Sun, Yingli Jiang, Xiaofeng Ayrapetov, Marina K. Moskwa, Patryk Yang, Shenghong Weinstock, David M. Price, Brendan D. TI The p400 ATPase regulates nucleosome stability and chromatin ubiquitination during DNA repair SO JOURNAL OF CELL BIOLOGY LA English DT Article ID DOUBLE-STRAND BREAKS; ZINC-FINGER NUCLEASES; HISTONE ACETYLTRANSFERASE; DAMAGE RESPONSE; MRE11-RAD50-NBS1 COMPLEX; ACETYLATION; ATM; PROTEIN; TIP60; SITES AB T he complexity of chromatin architecture presents a significant barrier to the ability of the DNA repair machinery to access and repair DNA double-strand breaks (DSBs). Consequently, remodeling of the chromatin landscape adjacent to DSBs is vital for efficient DNA repair. Here, we demonstrate that DNA damage destabilizes nucleosomes within chromatin regions that correspond to the gamma-H2AX domains surrounding DSBs. This nucleosome destabilization is an active process requiring the ATPase activity of the p400 SWI/SNF ATPase and histone acetylation by the Tip60 acetyltransferase. p400 is recruited to DSBs by a mechanism that is independent of ATM but requires mdc1. Further, the destabilization of nucleosomes by p400 is required for the RNF8-dependent ubiquitination of chromatin, and for the subsequent recruitment of brca1 and 53BP1 to DSBs. These results identify p400 as a novel DNA damage response protein and demonstrate that p400-mediated alterations in nucleosome and chromatin structure promote both chromatin ubiquitination and the accumulation of brca1 and 53BP1 at sites of DNA damage. C1 [Xu, Ye; Sun, Yingli; Jiang, Xiaofeng; Ayrapetov, Marina K.; Moskwa, Patryk; Yang, Shenghong; Price, Brendan D.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol,Div Genom Stabil & DNA Repair, Boston, MA 02115 USA. [Weinstock, David M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Price, BD (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Radiat Oncol,Div Genom Stabil & DNA Repair, 44 Binney St, Boston, MA 02115 USA. EM brendan_price@dfci.harvard.edu FU National Cancer Institute [CA64585, CA93602, T32 CA09078]; DOD FX This work was supported by grants from the National Cancer Institute (CA64585 and CA93602), the DOD Breast Cancer Program, and by a National Cancer Institute training grant to Y. Sun (T32 CA09078). NR 60 TC 91 Z9 98 U1 0 U2 17 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9525 J9 J CELL BIOL JI J. Cell Biol. PD OCT 4 PY 2010 VL 191 IS 1 BP 31 EP 43 DI 10.1083/jcb.201001160 PG 13 WC Cell Biology SC Cell Biology GA 660MU UT WOS:000282648500006 PM 20876283 ER PT J AU Farmer, P Frenk, J Knaul, FM Shulman, LN Alleyne, G Armstrong, L Atun, R Blayney, D Chen, L Feachem, R Gospodarowicz, M Gralow, J Gupta, S Langer, A Lob-Levyt, J Neal, C Mbewu, A Mired, D Piot, P Reddy, KS Sachs, JD Sarhan, M Seffrin, JR AF Farmer, Paul Frenk, Julio Knaul, Felicia M. Shulman, Lawrence N. Alleyne, George Armstrong, Lance Atun, Rifat Blayney, Douglas Chen, Lincoln Feachem, Richard Gospodarowicz, Mary Gralow, Julie Gupta, Sanjay Langer, Ana Lob-Levyt, Julian Neal, Claire Mbewu, Anthony Mired, Dina Piot, Peter Reddy, K. Srinath Sachs, Jeffrey D. Sarhan, Mahmoud Seffrin, John R. TI Expansion of cancer care and control in countries of low and middle income: a call to action SO LANCET LA English DT Article ID HEALTH SYSTEM REFORM; HIV PREVENTION; BREAST-CANCER; MEXICO; SETTINGS; LESSONS; TRENDS; WORLD AB Substantial inequalities exist in cancer survival rates across countries. In addition to prevention of new cancers by reduction of risk factors, strategies are needed to close the gap between developed and developing countries in cancer survival and the effects of the disease on human suffering. We challenge the public health community's assumption that cancers will remain untreated in poor countries, and note the analogy to similarly unfounded arguments from more than a decade ago against provision of HIV treatment. In resource-constrained countries without specialised services, experience has shown that much can be done to prevent and treat cancer by deployment of primary and secondary caregivers, use of off-patent drugs, and application of regional and global mechanisms for financing and procurement. Furthermore, several middle-income countries have included cancer treatment in national health insurance coverage with a focus on people living in poverty. These strategies can reduce costs, increase access to health services, and strengthen health systems to meet the challenge of cancer and other diseases. In 2009, we formed the Global Task Force on Expanded Access to Cancer Care and Control in Developing Countries, which is composed of leaders from the global health and cancer care communities, and is dedicated to proposal, implementation, and evaluation of strategies to advance this agenda. C1 [Farmer, Paul] Harvard Univ, Sch Med, Boston, MA USA. [Frenk, Julio; Langer, Ana] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Knaul, Felicia M.] Harvard Global Equ Initiat, Boston, MA 02115 USA. [Shulman, Lawrence N.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Alleyne, George] Pan Amer Hlth Org, Washington, DC USA. [Armstrong, Lance; Neal, Claire] Lance Armstrong Fdn, Austin, TX USA. [Atun, Rifat] Global Fund Fight AIDS TB & Malaria, Geneva, Switzerland. [Blayney, Douglas] Amer Soc Clin Oncol, Alexandria, VA USA. [Chen, Lincoln] China Med Board, Cambridge, MA USA. [Feachem, Richard] Univ Calif Berkeley, Global Hlth Grp, Berkeley, CA 94720 USA. [Feachem, Richard] Univ Calif San Francisco, Global Hlth Grp, San Francisco, CA 94143 USA. [Gospodarowicz, Mary] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. [Gralow, Julie] Seattle Canc Care Alliance, Seattle, WA USA. [Gupta, Sanjay] CNN, Atlanta, GA USA. [Lob-Levyt, Julian] Global Alliance Vaccine & Immunizat, Geneva, Switzerland. [Mbewu, Anthony] Global Forum Hlth Res, Geneva, Switzerland. [Mired, Dina] King Hussein Canc Fdn, Amman, Jordan. [Piot, Peter] Univ London Imperial Coll Sci Technol & Med, Inst Global Hlth, London, England. [Reddy, K. Srinath] Publ Hlth Fdn India, New Delhi, India. [Sachs, Jeffrey D.] Columbia Univ, Earth Inst, New York, NY USA. [Sarhan, Mahmoud] King Hussein Canc Ctr, Amman, Jordan. [Seffrin, John R.] Amer Canc Soc, Atlanta, GA 30329 USA. RP Knaul, FM (reprint author), Harvard Global Equ Initiat, 651 Huntington Ave,FXB Bldg 632, Boston, MA 02115 USA. EM felicia_knaul@harvard.edu FU Genentech; Sanofi-Aventis; Roche; Amgen; Novartis FX PF, JF, LNS, GA, LA, DW, LC, RF, AL, CN, AM, DM, PP, KSR, JDS, MS, and JRS declare that they have no conflicts of interest. FMK is associated with a non-profit programme in Mexico (Tomatelo a Pecho) to promote early detection of breast cancer; receives honoraria from the Mexican Health Foundation, which has submitted research grant applications to GlaxoSmithKline and Roche; and has been nominated to become a board member (unpaid) for the International Union Against Cancer. MG serves as a board member (unpaid) for the International Union Against Cancer. JG's institution has received grants from Genentech, Sanofi-Aventis, Roche, Amgen, and Novartis. SG is a board member of non-profit organisation LIVESTRONG, a staff member of Emory Clinic Department of Neurosurgery, chief medical correspondent for CNN, and a medical contributor to CBS and Time Magazine. NR 54 TC 205 Z9 208 U1 1 U2 28 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 J9 LANCET JI Lancet PD OCT 2 PY 2010 VL 376 IS 9747 BP 1186 EP 1193 DI 10.1016/S0140-6736(10)61152-X PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 663UN UT WOS:000282915700035 PM 20709386 ER PT J AU Grass, S Preuss, KD Wikowicz, A Terpos, E Ziepert, M Ahlgrimm, M Fadle, N Regitz, E Murawski, N Dimopoulos, MA Treon, SP Hunter, ZR Pfreundschuh, M AF Grass, S. Preuss, K-D Wikowicz, A. Terpos, E. Ziepert, M. Ahlgrimm, M. Fadle, N. Regitz, E. Murawski, N. Dimopoulos, M. A. Treon, S. P. Hunter, Z. R. Pfreundschuh, M. TI Association of hyperphosphorylated paratarg-7, the first dominantly inherited risk factor in hematological neoplasia with IgM-MGUS and Waldenstrom's macroglobulinemia (WM) SO ONKOLOGIE LA English DT Meeting Abstract C1 [Grass, S.; Preuss, K-D; Wikowicz, A.; Ahlgrimm, M.; Fadle, N.; Regitz, E.; Murawski, N.; Pfreundschuh, M.] Univ Saarland, Sch Med, Dep Internal Med 1, Jose Carreras Ctr Immuno & Gene Therapy, D-6650 Homburg, Germany. [Terpos, E.; Dimopoulos, M. A.] Univ Athens, Sch Med, Dept Clin Therapeut, GR-11527 Athens, Greece. [Ziepert, M.] IMISE, Leipzig, Germany. [Treon, S. P.; Hunter, Z. R.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Bing Ctr Waldenstroms Macroglobulinemia, Boston, MA 02115 USA. RI Hunter, Zachary/H-3018-2013 OI Hunter, Zachary/0000-0002-1689-1691 NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0378-584X J9 ONKOLOGIE JI Onkologie PD OCT PY 2010 VL 33 SU 6 BP 281 EP 281 PG 1 GA 664UN UT WOS:000282988401351 ER PT J AU Cucchiarini, M Menger, MD Kohn, D Trippel, SB Terwilliger, EF Madry, H AF Cucchiarini, M. Menger, M. D. Kohn, D. Trippel, S. B. Terwilliger, E. F. Madry, H. TI DIRECT RAAV-MEDIATED IGF-I OVEREXPRESSION ENHANCES ARTICULAR CARTILAGE REPAIR IN VIVO SO OSTEOARTHRITIS AND CARTILAGE LA English DT Meeting Abstract CT World Congress of the OsteoArthritis-Research-Society-International CY SEP 23-26, 2010 CL Brussels, BELGIUM SP OsteoArthritis Res Soc Int C1 [Cucchiarini, M.; Kohn, D.; Madry, H.] Inst Expt Orthopaed, Homburg, Germany. [Menger, M. D.] Dept Clin & Expt Surgery, Homburg, Germany. [Trippel, S. B.] Indiana Univ, Dept Orthopaed Surg, Indianapolis, IN 46204 USA. [Terwilliger, E. F.] BIDMC, Harvard Inst Med, Div Expt Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 1063-4584 J9 OSTEOARTHR CARTILAGE JI Osteoarthritis Cartilage PD OCT PY 2010 VL 18 SU 2 BP S81 EP S81 PG 1 WC Orthopedics; Rheumatology SC Orthopedics; Rheumatology GA 670UN UT WOS:000283452900188 ER PT J AU Hoofs, JC Shiffman, ML Goodman, Z Kleiner, DE Stoddard, AM Dienstag, JL AF Hoofs, John C. Shiffman, Mitchell L. Goodman, Zachary Kleiner, David E. Stoddard, Anne M. Dienstag, Jules L. TI RATE OF PROGRESSION OF HEPATIC FIBROSIS IN PATIENT WITH CHRONIC HEPATITIS C (CHC) PREDICTS NON-HCC AND HCC OUTCOMES: RESULTS FROM THE HALT-C TRIAL SO HEPATOLOGY LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 29-NOV 02, 2010 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Hoofs, John C.] Univ Calif Irvine, Orange, CA 92668 USA. [Shiffman, Mitchell L.] Bon Secours Hlth Syst, Liver Inst Virginia, Newport News, VA USA. [Goodman, Zachary] Inova Fairfax Hosp, Ctr Liver Dis, Falls Church, VA USA. [Kleiner, David E.] NCI, Pathol Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. [Stoddard, Anne M.] New England Res Inst Inc, Watertown, MA USA. [Dienstag, Jules L.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2010 VL 52 IS 4 SU S MA 178 BP 412A EP 412A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 740EY UT WOS:000288775600184 ER PT J AU Speliotes, EK Yerges-Armstrong, LM Wu, J Hernaez, R Kim, LJ Palmer, C Harris, TB Eiriksdottir, G Garcia, ME Launer, LJ Nalls, MA Clark, JM Mitchell, BD Shuldiner, AR Butler, JL Hoffmann, U Massaro, JM O'Donnell, CJ Sahani, DV Carri, J Feitosa, MF Gudnason, V Fox, CS Smith, AV Kao, WHL Hirschhorn, JN Borecki, IB AF Speliotes, Elizabeth K. Yerges-Armstrong, Laura M. Wu, Jun Hernaez, Ruben Kim, Lauren J. Palmer, Cameron Harris, Tamara B. Eiriksdottir, Gudny Garcia, Melissa E. Launer, Lenore J. Nalls, Michael A. Clark, Jeanne M. Mitchell, Braxton D. Shuldiner, Alan R. Butler, Johannah L. Hoffmann, Udo Massaro, Joseph M. O'Donnell, Christopher J. Sahani, Dushyant V. Carri, Jeffrey Feitosa, Mary F. Gudnason, Vilmundur Fox, Caroline S. Smith, Albert V. Kao, Wen Hong L. Hirschhorn, Joel N. Borecki, Ingrid B. TI GENOME-WIDE ASSOCIATION ANALYSIS IDENTIFIES VARIANTS ASSOCIATED WITH NONALCOHOLIC FATTY LIVER DISEASE THAT HAVE DISTINCT EFFECTS ON SERUM LIPIDS SO HEPATOLOGY LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 29-NOV 02, 2010 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Speliotes, Elizabeth K.; Butler, Johannah L.] Broad Inst, Cambridge, MA USA. [Yerges-Armstrong, Laura M.; Mitchell, Braxton D.; Shuldiner, Alan R.] Univ Maryland, Sch Med, Dept Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA. [Wu, Jun; Feitosa, Mary F.; Borecki, Ingrid B.] Washington Univ, Div Stat Genom, St Louis, MO USA. [Hernaez, Ruben; Kao, Wen Hong L.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. [Hernaez, Ruben; Clark, Jeanne M.] Johns Hopkins Univ Hosp, Div Gen Internal Med, Baltimore, MD 21287 USA. [Kim, Lauren J.; Harris, Tamara B.; Garcia, Melissa E.; Launer, Lenore J.] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, NIH, Bethesda, MD 20892 USA. [Palmer, Cameron; Butler, Johannah L.; Hirschhorn, Joel N.] Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA. [Palmer, Cameron; Butler, Johannah L.; Hirschhorn, Joel N.] Childrens Hosp, Div Genet, Boston, MA 02115 USA. [Palmer, Cameron; Butler, Johannah L.; Hirschhorn, Joel N.] Childrens Hosp, Program Genom, Boston, MA 02115 USA. [Eiriksdottir, Gudny; Gudnason, Vilmundur; Smith, Albert V.] Iceland Heart Assoc, IS-201 Kopavogur, Iceland. [Nalls, Michael A.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. [Clark, Jeanne M.; Kao, Wen Hong L.] Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA. [Shuldiner, Alan R.] Vet Adm Med Ctr, GRECC, Baltimore, MD 21218 USA. [Hoffmann, Udo; Sahani, Dushyant V.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Massaro, Joseph M.; O'Donnell, Christopher J.; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Massaro, Joseph M.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [O'Donnell, Christopher J.; Fox, Caroline S.] NHLBI, Div Intramural Res, Bethesda, MD 20892 USA. [Carri, Jeffrey] Wake Forest Univ, Sch Med, Dept Radiol Sci, Winston Salem, NC 27109 USA. [Carri, Jeffrey] Wake Forest Univ, Sch Med, Dept Internal Med Cardiol, Winston Salem, NC 27109 USA. [Carri, Jeffrey] Wake Forest Univ, Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27109 USA. [Gudnason, Vilmundur] Univ Iceland, IS-101 Reykjavik, Iceland. [Hirschhorn, Joel N.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA. RI Hernaez, Ruben/C-4039-2014; Gudnason, Vilmundur/K-6885-2015; Feitosa, Mary/K-8044-2012 OI Hernaez, Ruben/0000-0002-1518-4020; Gudnason, Vilmundur/0000-0001-5696-0084; Feitosa, Mary/0000-0002-0933-2410 NR 0 TC 1 Z9 1 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2010 VL 52 IS 4 SU S MA 254 BP 450A EP 450A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 740EY UT WOS:000288775600260 ER PT J AU Uygun, BE Price, G Guzzardi, MA Izamis, ML Soto-Gutierrez, A Yagi, H Yarmush, ML Uygun, K AF Uygun, Basak E. Price, Gavrielle Guzzardi, Maria Angela Izamis, Maria-Louisa Soto-Gutierrez, Alejandro Yagi, Hiroshi Yarmush, Martin L. Uygun, Korkut TI ENGINEERING OF A TRANSPLANTABLE LIVER GRAFT SO HEPATOLOGY LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 29-NOV 02, 2010 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Uygun, Basak E.; Price, Gavrielle; Guzzardi, Maria Angela; Izamis, Maria-Louisa; Soto-Gutierrez, Alejandro; Yagi, Hiroshi; Yarmush, Martin L.; Uygun, Korkut] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Shriners Hosp Children, Boston, MA USA. RI Guzzardi, Maria-Angela/K-1389-2016 OI Guzzardi, Maria-Angela/0000-0001-9574-5088 NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2010 VL 52 IS 4 SU S MA 293 BP 468A EP 468A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 740EY UT WOS:000288775600299 ER PT J AU Lomonaco, R Ortiz-Lopez, C Orsak, B Finch, J King, J Cusi, K AF Lomonaco, Romina Ortiz-Lopez, Carolina Orsak, Beverly Finch, Joan King, James Cusi, Kenneth TI PREVALENCE OF NAFLD BY MRS AND ROLE OF INSULIN RESISTANCE AND T2DM IN THE DEVELOPMENT OF NASH IN A PREDOMINANTLY HISPANIC POPULATION SO HEPATOLOGY LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 29-NOV 02, 2010 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Lomonaco, Romina; Ortiz-Lopez, Carolina; Orsak, Beverly; King, James; Cusi, Kenneth] Univ Texas Hlth Sci Ctr San Antonio, Diabet Div, San Antonio, TX 78229 USA. [Finch, Joan; Cusi, Kenneth] Vet Adm Med Ctr, Diabet Div, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2010 VL 52 IS 4 SU S MA 624 BP 619A EP 620A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 740EY UT WOS:000288775600623 ER PT J AU Ortiz-Lopez, C Webb, A Lomonaco, R Orsak, B Darland, CM Finch, J Diaz, N Cusi, K AF Ortiz-Lopez, Carolina Webb, Amy Lomonaco, Romina Orsak, Beverly Darland, Celia M. Finch, Joan Diaz, Norma Cusi, Kenneth TI ABNORMAL GLUCOSE METABOLISM IS FREQUENTLY OVERLOOKED IN PATIENTS WITH NASH AND ASSOCIATED WITH SEVERE HEPATIC AND ADIPOSE TISSUE INSULIN RESISTANCE SO HEPATOLOGY LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 29-NOV 02, 2010 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Ortiz-Lopez, Carolina; Webb, Amy; Lomonaco, Romina; Orsak, Beverly; Finch, Joan; Cusi, Kenneth] Univ Texas Hlth Sci Ctr San Antonio, Diabet Div, San Antonio, TX 78229 USA. [Webb, Amy; Darland, Celia M.; Finch, Joan; Diaz, Norma; Cusi, Kenneth] Audie L Murphy Vet Affairs Hosp, Diabet Div, San Antonio, TX USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2010 VL 52 IS 4 SU S MA 628 BP 621A EP 622A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 740EY UT WOS:000288775600627 ER PT J AU Long, M Rutherford, AE Chung, RI Corey, KE AF Long, Michelle Rutherford, Anna E. Chung, Raymond I. Corey, Kathleen E. TI THE PREVALENCE AND ASSOCIATION OF HYPOTHYROIDISM IN PATIENTS WITH BIOPSY-PROVEN NONALCOHOLIC FATTY LIVER DISEASE OR NONALCOHOLIC STEATOHEPATITIS SO HEPATOLOGY LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 29-NOV 02, 2010 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Long, Michelle; Chung, Raymond I.; Corey, Kathleen E.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rutherford, Anna E.] Brigham Women Hosp, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2010 VL 52 IS 4 SU S MA 705 BP 657A EP 657A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 740EY UT WOS:000288775601024 ER PT J AU Deuffic-Burban, S Deltenre, P Buti, M Stroffolini, T Parkes, J Muhlberger, N Siebert, U Moreno, C Hatzakis, A Rosenberg, WM Zeuzem, S Mathurin, P AF Deuffic-Burban, Sylvie Deltenre, Pierre Buti, Maria Stroffolini, Tommaso Parkes, Julie Muehlberger, Nikolai Siebert, Uwe Moreno, Christophe Hatzakis, Angelos Rosenberg, William M. Zeuzem, Stefan Mathurin, Philippe TI HCV BURDEN IN EUROPE: IMPACT OF NATIONAL TREATMENT PRACTICES ON FUTURE HCV-RELATED MORBIDITY AND MORTALITY THROUGH A MODELING APPROACH SO HEPATOLOGY LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 29-NOV 02, 2010 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Deuffic-Burban, Sylvie; Mathurin, Philippe] INSERM, U995, F-59045 Lille, France. [Deuffic-Burban, Sylvie] Univ Lille Nord France, Lille, France. [Deltenre, Pierre; Mathurin, Philippe] CHRU Lille, Hop Huriez, Lille, France. [Deltenre, Pierre] Hop Jolimont, Haine St Paul, Belgium. [Buti, Maria] Hosp Gen Univ Valle Hebron, Barcelona, Spain. [Buti, Maria] Ciberehd Inst Carlos III, Barcelona, Spain. [Stroffolini, Tommaso] Policlin Umberto 1, Rome, Italy. [Parkes, Julie] Univ Southampton, Sch Med, Southampton, Hants, England. [Muehlberger, Nikolai; Siebert, Uwe] Univ Hlth Sci Med Informat & Technol, Innsbruck, Austria. [Siebert, Uwe] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Moreno, Christophe] ULB, Hop Erasme, Brussels, Belgium. [Hatzakis, Angelos] Univ Athens, Sch Med, GR-11527 Athens, Greece. [Rosenberg, William M.] UCL, London, England. [Zeuzem, Stefan] Goethe Univ Hosp, Frankfurt, Germany. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2010 VL 52 IS 4 SU S MA 750 BP 678A EP 679A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 740EY UT WOS:000288775601069 ER PT J AU Kim, AY Hills-Evans, K Nagami, EH Reyor, LL Wurcel, A McGovern, BH AF Kim, Arthur Y. Hills-Evans, Kelsey Nagami, Ellen H. Reyor, Laura L. Wurcel, Alysse McGovern, Barbara H. TI RACIAL DIFFERENCES IN DRUG USE BEHAVIORS AND RISK FOR HCV INFECTION AMONG MASSACHUSETTS INMATES SO HEPATOLOGY LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 29-NOV 02, 2010 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Kim, Arthur Y.; Hills-Evans, Kelsey; Reyor, Laura L.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. [Nagami, Ellen H.; McGovern, Barbara H.] Lemuel Shattuck Hosp, Div Infect Dis, Jamaica Plain, MA USA. [Kim, Arthur Y.; Nagami, Ellen H.] Harvard Univ, Ctr AIDS Res, Boston, MA 02115 USA. [Wurcel, Alysse] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2010 VL 52 IS 4 SU S MA 752 BP 679A EP 680A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 740EY UT WOS:000288775601071 ER PT J AU Zhao, H Tai, AW Lin, WY Peng, LF Zhang, LL Goto, K Shao, RX Jilg, N Chung, RT AF Zhao, Hong Tai, Andrew W. Lin, Wenyu Peng, Lee F. Zhang, Leiliang Goto, Kaku Shao, Run-Xuan Jilg, Nikolaus Chung, Raymond T. TI A FUNCTIONAL GENOMIC SCREEN REVEALS NOVEL HOST GENES THAT MEDIATE INTERFERON-alpha ' S ANTIVIRAL EFFECTS AGAINST HEPATITIS C VIRUS SO HEPATOLOGY LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 29-NOV 02, 2010 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Zhao, Hong; Tai, Andrew W.; Lin, Wenyu; Peng, Lee F.; Zhang, Leiliang; Goto, Kaku; Shao, Run-Xuan; Jilg, Nikolaus; Chung, Raymond T.] Mass Gen Hosp, Dept Med, Boston, MA USA. [Zhao, Hong] Peking Univ First Hosp, Dept Infect Dis, Beijing, Peoples R China. [Tai, Andrew W.] Univ Michigan, Div Gastroenterol, Ann Arbor, MI 48109 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2010 VL 52 IS 4 SU S MA 838 BP 724A EP 724A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 740EY UT WOS:000288775601158 ER PT J AU Ciuffreda, DB zur Wiesch, JS Qin, LZ Kroy, DC Ingber, S Foote, P Kwok, WW Reyor, LL Hills-Evans, K Chung, R Kim, AY Lauer, GM AF Ciuffreda, Donatella B. zur Wiesch, Julian Schulze Qin, Lizeng Kroy, Daniela C. Ingber, Susan Foote, Peter Kwok, William W. Reyor, Laura L. Hills-Evans, Kelsey Chung, Ray Kim, Arthur Y. Lauer, Georg M. TI LOSS OF HCV-SPECIFIC CD4+T CELLS IN ACUTE CHRONICALLY EVOLVING INFECTION IS NOT ATTRIBUTABLE TO HIGH EXPRESSION OF INHIBITORY MOLECULES SO HEPATOLOGY LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 29-NOV 02, 2010 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Ciuffreda, Donatella B.; Qin, Lizeng; Kroy, Daniela C.; Ingber, Susan; Foote, Peter; Reyor, Laura L.; Hills-Evans, Kelsey; Chung, Ray; Lauer, Georg M.] Massachusetts Gen Hosp, Gastrointestinal Div, Boston, MA 02114 USA. [zur Wiesch, Julian Schulze] Univ Hosp, Med Dept 1, Hamburg Eppendorf, Germany. [Kwok, William W.] Benaroya Inst, Seattle, WA USA. [Kim, Arthur Y.] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2010 VL 52 IS 4 SU S MA 858 BP 733A EP 734A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 740EY UT WOS:000288775601177 ER PT J AU Shao, RX Zhang, LL Goto, K Chen, WC Jilg, N Zhao, H Mendez-Navarro, J Kumthip, K Peng, LF Chung, RT AF Shao, Run-Xuan Zhang, Leiliang Goto, Kaku Chen, Wen-Chi Jilg, Nikolaus Zhao, Hong Mendez-Navarro, Jorge Kumthip, Kattareeya Peng, Lee F. Chung, Raymond T. TI SOCS1 ABROGATES IFN'S ANTIVIRAL EFFECT ON HEPATITIS C VIRUS REPLICATION SO HEPATOLOGY LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 29-NOV 02, 2010 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Shao, Run-Xuan; Zhang, Leiliang; Goto, Kaku; Chen, Wen-Chi; Jilg, Nikolaus; Zhao, Hong; Mendez-Navarro, Jorge; Kumthip, Kattareeya; Peng, Lee F.; Chung, Raymond T.] Massachusetts Gen Hosp, Gastrointestinal Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2010 VL 52 IS 4 SU S MA 866 BP 737A EP 737A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 740EY UT WOS:000288775601185 ER PT J AU Zhang, LL Jilg, N Shao, RX Lin, WY Zhao, H Goto, K Chen, WC Chung, RT AF Zhang, Leiliang Jilg, Nikolaus Shao, Run-Xuan Lin, Wenyu Zhao, Hong Goto, Kaku Chen, Wen-Chi Chung, Raymond T. TI IL28B INHIBITS HEPATITIS C VIRUS REPLICATION THROUGH JAK-STAT PATHWAY SO HEPATOLOGY LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 29-NOV 02, 2010 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Zhang, Leiliang; Jilg, Nikolaus; Shao, Run-Xuan; Lin, Wenyu; Zhao, Hong; Goto, Kaku; Chen, Wen-Chi; Chung, Raymond T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med,Gastrointestinal Unit, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2010 VL 52 IS 4 SU S MA 902 BP 753A EP 753A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 740EY UT WOS:000288775601221 ER PT J AU Vermehren, J Yu, ML Monto, A Yao, JD Anderson, C Bertuzis, R Schneider, G Sarrazin, C AF Vermehren, Johannes Yu, Ming-Lung Monto, Alexander Yao, Joseph D. Anderson, Christopher Bertuzis, Rasa Schneider, George Sarrazin, Christoph TI CLINICAL UTILITY OF THE REALTIME HCV ASSAY (ABBOTT MOLECULAR) FOR RESPONSE-GUIDED THERAPY IN PATIENTS INFECTED WITH HCV GENOTYPES 1, 2, OR 3 AND TREATED WITH PEGINTERFERON-ALFA PLUS RIBAVIRIN (PEGIFN/RBV) SO HEPATOLOGY LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 29-NOV 02, 2010 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Vermehren, Johannes; Sarrazin, Christoph] Klinikum JW Goethe Univ, Med Klin 1, Frankfurt, Germany. [Yu, Ming-Lung] Kaohsiung Med Univ Hosp, Kaohsiung, Taiwan. [Monto, Alexander] San Francisco VA Med Ctr, San Francisco, CA USA. [Yao, Joseph D.] Mayo Med Labs, Rochester, MN USA. [Anderson, Christopher; Bertuzis, Rasa; Schneider, George] Abbott Mol, Des Plaines, IL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2010 VL 52 IS 4 SU S MA 972 BP 789A EP 790A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 740EY UT WOS:000288775601290 ER PT J AU Goto, K Zhang, LL Shao, RX Lin, WY Jilg, N Zhao, H Chen, WC Peng, LF Chung, RT AF Goto, Kaku Zhang, Leiliang Shao, Run Xuan Lin, Wenyu Jilg, Nikolaus Zhao, Hong Chen, Wen-Chi Peng, Lee F. Chung, Raymond T. TI THE STRESS-ACTIVATED KINASE SNARK RECIPROCALLY REGULATES HCV REPLICATION SO HEPATOLOGY LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 29-NOV 02, 2010 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Goto, Kaku; Zhang, Leiliang; Shao, Run Xuan; Lin, Wenyu; Jilg, Nikolaus; Zhao, Hong; Chen, Wen-Chi; Peng, Lee F.; Chung, Raymond T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2010 VL 52 IS 4 SU S MA 1032 BP 819A EP 819A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 740EY UT WOS:000288775601350 ER PT J AU Chung, WJ Jang, BK Hwang, J Tai, AW Lin, W Shao, RX Chung, RT AF Chung, Woo Jin Jang, Byoung Kuk Hwang, Jaeseok Tai, Andrew W. Lin, Wenyu Shao, Run Xuan Chung, Raymond T. TI PI3-KINASE INHIBITION BLOCKS INTERFERON SIGNALING IN HCV INFECTED HEPATOCYTES SO HEPATOLOGY LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 29-NOV 02, 2010 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Chung, Woo Jin; Jang, Byoung Kuk; Hwang, Jaeseok] Keimyung Univ, Dongsan Med Ctr, Taegu, South Korea. [Tai, Andrew W.] Univ Michigan, Dept Internal Med, Div Gastroenterol, Ann Arbor, MI 48109 USA. [Lin, Wenyu; Shao, Run Xuan; Chung, Raymond T.] Harvard Univ, Sch Med, Dept Med, Massachusetts Gen Hosp,GI Unit, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2010 VL 52 IS 4 SU S MA 1050 BP 827A EP 827A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 740EY UT WOS:000288775601368 ER PT J AU Enestvedt, B Enestvedt, CK Faigel, DO Orloff, SL AF Enestvedt, Brintha Enestvedt, C. Kristian Faigel, Douglas O. Orloff, Susan L. TI RISK FACTORS FOR BILIARY STRICTURE POST ORTHOTOPIC LIVER TRANSPLANTATION: A SINGLE CENTER EXPERIENCE SO HEPATOLOGY LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 29-NOV 02, 2010 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Enestvedt, Brintha; Enestvedt, C. Kristian; Faigel, Douglas O.; Orloff, Susan L.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Orloff, Susan L.] Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2010 VL 52 IS 4 SU S MA 1073 BP 838A EP 838A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 740EY UT WOS:000288775601391 ER PT J AU Kim, CW Torrey, K Valiga, ME Cho, H Lee, CD Chang, KM AF Kim, Chang Wook Torrey, Keith Valiga, Mary E. Cho, Hyosun Lee, Chang Don Chang, Kyong-Mi TI HBV-SPECIFIC T CELL RESPONSE OF HCV-INFECTED PATIENTS WITH ISOLATED ANTI-HBC AND COMBINED ANTI-HBC/ANTI-HBS ANTIBODY RESPONSE SO HEPATOLOGY LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 29-NOV 02, 2010 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Torrey, Keith; Valiga, Mary E.; Cho, Hyosun; Chang, Kyong-Mi] Philadelphia VA Med Ctr, GI Hepatol Res Ctr, Philadelphia, PA USA. [Kim, Chang Wook; Torrey, Keith; Valiga, Mary E.; Cho, Hyosun; Chang, Kyong-Mi] Univ Penn, Philadelphia, PA 19104 USA. [Kim, Chang Wook; Lee, Chang Don] Catholic Univ Korea, Seoul, South Korea. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2010 VL 52 IS 4 SU S MA 1372 BP 980A EP 981A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 740EY UT WOS:000288775601702 ER PT J AU King, LY Hynan, LS Vedvyas, C Lin, WY Lee, WM Rutherford, AE Chung, RT AF King, Lindsay Y. Hynan, Linda S. Vedvyas, Chetan Lin, Wenyu Lee, William M. Rutherford, Anna E. Chung, Raymond T. TI A CLINICAL PREDICTION RULE FOR OUTCOME IN ACUTE LIVER FAILURE SO HEPATOLOGY LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 29-NOV 02, 2010 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [King, Lindsay Y.; Lin, Wenyu; Chung, Raymond T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Rutherford, Anna E.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Hynan, Linda S.; Lee, William M.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [King, Lindsay Y.; Vedvyas, Chetan; Rutherford, Anna E.; Chung, Raymond T.] Harvard Univ, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2010 VL 52 IS 4 SU S MA 1606 BP 1087A EP 1087A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 740EY UT WOS:000288775602226 ER PT J AU Lennerz, JK Chapman, WC Brunt, EM AF Lennerz, Jochen K. Chapman, William C. Brunt, Elizabeth M. TI PERINODULAR K19 PATTERN AND EPITHELIAL-MESENCHYMAL TRANSITION (EMT) IN CIRRHOTIC STROMA PARALLELS HEPATOCARCINOGENESIS IN NODULES SO HEPATOLOGY LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 29-NOV 02, 2010 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Lennerz, Jochen K.] Harvard Univ, Sch Med, Dept Pathol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Lennerz, Jochen K.; Brunt, Elizabeth M.] Washington Univ, Dept Pathol, St Louis, MO USA. [Chapman, William C.] Washington Univ, Dept Surg, St Louis, MO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2010 VL 52 IS 4 SU S MA 1716 BP 1138A EP 1138A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 740EY UT WOS:000288775602336 ER PT J AU Kaplan, DE Daruich, J Jalali, Z Rafiullah Nunez, M Vogel, M Vispo, E Barreiro, P Rockstroh, JK Mauss, S Brau, N AF Kaplan, David E. Daruich, Jorge Jalali, Ziba Rafiullah Nunez, Marina Vogel, Martin Vispo, Eugenia Barreiro, Pablo Rockstroh, Juergen K. Mauss, Stefan Braeu, Norbert TI AGE AND HEPATOCELLULAR CARCINOMA IN HIV-INFECTED PATIENTS SO HEPATOLOGY LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 29-NOV 02, 2010 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Kaplan, David E.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Kaplan, David E.] Univ Penn, Sch Med, Div Gastroenterol, Philadelphia, PA 19104 USA. [Daruich, Jorge] Univ Buenos Aires, Secc Hepatol, Buenos Aires, DF, Argentina. [Jalali, Ziba] Univ Nebraska Med Ctr, Div Infect Dis, Omaha, NE USA. [Rafiullah; Braeu, Norbert] Bronx VA Med Ctr, Bronx, NY USA. [Nunez, Marina] Wake Forest Univ, Div Infect Dis, Winston Salem, NC 27109 USA. [Vogel, Martin; Rockstroh, Juergen K.] Univ Klinikum Bonn, Bonn, Germany. [Vispo, Eugenia; Barreiro, Pablo] Hosp Carlos III, Madrid, Spain. [Mauss, Stefan] Dusseldorf Ctr HIV & HepatoGastroenterol, Dusseldorf, Germany. [Braeu, Norbert] Mt Sinai Sch Med, Div Infect Dis, New York, NY USA. [Braeu, Norbert] Mt Sinai Sch Med, Div Liver Dis, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2010 VL 52 IS 4 SU S MA 1795 BP 1174A EP 1175A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 740EY UT WOS:000288775602413 ER PT J AU Patwardhan, V Paul, S Corey, KE Mazhar, SM Thiim, M Richter, JM Chung, RT AF Patwardhan, Vilas Paul, Sonali Corey, Kathleen E. Mazhar, Sameer M. Thiim, Michael Richter, James M. Chung, Raymond T. TI HEPATOCELLULAR CARCINOMA SCREENING RATES IN CIRRHOTIC PATIENTS DIFFER BY SPECIALTY PRACTICE SO HEPATOLOGY LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 29-NOV 02, 2010 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Patwardhan, Vilas; Paul, Sonali; Corey, Kathleen E.; Mazhar, Sameer M.; Thiim, Michael; Richter, James M.; Chung, Raymond T.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2010 VL 52 IS 4 SU S MA 1952 BP 1249A EP 1249A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 740EY UT WOS:000288775602570 ER PT J AU Lin, WY Wu, GY Weinberg, EM Li, SY Peng, LF Mendez-Navarro, J Chen, WC Jilg, N Zhao, H Goto, K Zhang, LL Kumthip, K Schuppan, D Chung, RT AF Lin, Wenyu Wu, Guoyang Weinberg, Ethan M. Li, Shaoyong Peng, Lee F. Mendez-Navarro, Jorge Chen, Wen-Chi Jilg, Nikolaus Zhao, Hong Goto, Kaku Zhang, Leiliang Kumthip, Kattareeya Schuppan, Detlef Chung, Raymond T. TI HIV AND HCV INCREASE HEPATIC FIBROSIS PROGRESSION IN HEPATIC STELLATE CELLS AND HEPATOMA CELLS VIA ROS AND NF kappa B INDUCTION SO HEPATOLOGY LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 29-NOV 02, 2010 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Lin, Wenyu; Wu, Guoyang; Weinberg, Ethan M.; Peng, Lee F.; Mendez-Navarro, Jorge; Chen, Wen-Chi; Jilg, Nikolaus; Zhao, Hong; Goto, Kaku; Zhang, Leiliang; Kumthip, Kattareeya; Chung, Raymond T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. [Wu, Guoyang] Xiamen Univ, Zhongshan Hosp, Xiamen, Fujian, Peoples R China. [Li, Shaoyong; Schuppan, Detlef] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2010 VL 52 IS 4 SU S MA 1982 BP 1263A EP 1263A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 740EY UT WOS:000288775602600 ER PT J AU Nevzorova, Y Bangen, JM Gassler, N Haas, U Hu, W Weiskirchen, R Tacke, F Sicinski, P Trautwein, C Liedtke, C AF Nevzorova, Yulia Bangen, Joerg-Martin Gassler, Nikolaus Haas, Ute Hu, Wei Weiskirchen, Ralf Tacke, Frank Sicinski, Peter Trautwein, Christian Liedtke, Christian TI CONTRIBUTION OF E-TYPE CYCLINS IN HEPATIC FIBROSIS IN HUMAN AND MICE SO HEPATOLOGY LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 29-NOV 02, 2010 CL Boston, MA SP Amer Assoc Study Liver Dis C1 [Nevzorova, Yulia; Bangen, Joerg-Martin; Haas, Ute; Hu, Wei; Tacke, Frank; Trautwein, Christian; Liedtke, Christian] Univ Hosp Aachen, Dept Med 3, Aachen, Germany. [Gassler, Nikolaus] Univ Hosp Aachen, Inst Pathol, Aachen, Germany. [Weiskirchen, Ralf] Univ Hosp Aachen, Inst Clin Chem & Pathobiochem, Aachen, Germany. [Sicinski, Peter] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2010 VL 52 IS 4 SU S MA 2003 BP 1272A EP 1272A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 740EY UT WOS:000288775602621 ER PT J AU Dougherty, DD AF Dougherty, Darin D. TI THIS ISSUE: Deep Brain Stimulation SO PSYCHIATRIC ANNALS LA English DT Editorial Material C1 [Dougherty, Darin D.] Massachusetts Gen Hosp, Neurotherapeut Div, Dept Psychiat, Boston, MA 02114 USA. [Dougherty, Darin D.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA. RP Dougherty, DD (reprint author), MIT, Cambridge, MA 02139 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0048-5713 J9 PSYCHIAT ANN JI Psychiatr. Ann. PD OCT PY 2010 VL 40 IS 10 BP 458 EP 467 DI 10.3928/00485713-20100924-03 PG 3 WC Psychiatry SC Psychiatry GA 736IQ UT WOS:000288487300002 ER PT J AU Cusin, C Evans, KC Carpenter, LL Greenberg, BD Malone, DA Eskandar, E Dougherty, DD AF Cusin, Cristina Evans, Karleyton C. Carpenter, Linda L. Greenberg, Benjamin D. Malone, Donald A., Jr. Eskandar, Emad Dougherty, Darin D. TI Deep Brain Stimulation for Treatment Resistant Depression: The Role of the Ventral Capsule/Ventral Striatum SO PSYCHIATRIC ANNALS LA English DT Article ID OBSESSIVE-COMPULSIVE DISORDER; SUBGENUAL ANTERIOR CINGULATE; TERM-FOLLOW-UP; POTENTIAL PREDICTORS; MAJOR DEPRESSION; CINGULOTOMY; CAPSULOTOMY; TRIAL C1 [Cusin, Cristina; Evans, Karleyton C.; Greenberg, Benjamin D.] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Malone, Donald A., Jr.; Eskandar, Emad] Brown Univ, Dept Psychiat, Butler Hosp, Providence, RI 02912 USA. [Dougherty, Darin D.] Cleveland Clin Fdn, Dept Psychiat, Cleveland, OH 44195 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Neurosurg, Cambridge, MA 02138 USA. RP Dougherty, DD (reprint author), Massachusetts Gen Hosp, Dept Psychiat, CNY2612,149 13th St, Charlestown, MA 02129 USA. EM ddougherty@partners.org; ddougherty@partners.org NR 23 TC 1 Z9 1 U1 3 U2 6 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0048-5713 J9 PSYCHIAT ANN JI Psychiatr. Ann. PD OCT PY 2010 VL 40 IS 10 BP 477 EP 484 DI 10.3928/00485713-20100924-04 PG 8 WC Psychiatry SC Psychiatry GA 736IQ UT WOS:000288487300003 ER PT J AU Kramer, B Jouldjian, S Wang, M Mitchell, M Finke, B AF Kramer, B. Jouldjian, S. Wang, M. Mitchell, M. Finke, B. TI A MODEL FOR THE USE OF VETERANS HEALTH AFFAIRS AND/OR INDIAN HEALTH SERVICE BY OLDER AMERICAN INDIAN AND ALASKA NATIVE VETERANS SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Kramer, B.; Jouldjian, S.; Wang, M.; Mitchell, M.] VA Greater Angeles Healthcare Syst, Los Angeles, CA USA. [Kramer, B.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [Finke, B.] Indian Hlth Serv, Nashville, TN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 16 EP 16 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006701076 ER PT J AU Spira, AP Stone, KL Redline, S Ensrud, K Yaffe, K AF Spira, A. P. Stone, K. L. Redline, S. Ensrud, K. Yaffe, K. TI ACTIGRAPHIC SLEEP AND NEUROPSYCHOLOGICAL TEST PERFORMANCE IN VERY OLD WOMEN SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Spira, A. P.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD USA. [Stone, K. L.] Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA. [Redline, S.] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Ensrud, K.] Univ Minnesota, Minneapolis, MN USA. [Ensrud, K.] Minnepolis VA Med Ctr, Minneapolis, MN USA. [Yaffe, K.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Yaffe, K.] San Francisco VA Med Ctr, San Francisco, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 37 EP 37 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006701178 ER PT J AU Yaffe, K Laffan, A Harrison, SL Spira, AP Ensrud, K Ancoli-Israel, S Redline, S Stone, KL AF Yaffe, K. Laffan, A. Harrison, S. Litwack Spira, A. P. Ensrud, K. Ancoli-Israel, S. Redline, S. Stone, K. L. TI SLEEP DISORDERED BREATHING, HYPOXIA, AND RISK OF MILD COGNITIVE IMPAIRMENT & DEMENTIA IN OLDER WOMEN SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Yaffe, K.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Yaffe, K.] San Francisco VA Med Ctr, San Francisco, CA USA. [Laffan, A.; Harrison, S. Litwack; Stone, K. L.] Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA. [Spira, A. P.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Ensrud, K.] Univ Minnesota, Minneapolis, MN USA. [Ensrud, K.] Minneapolis VA Med Ctr, Minneapolis, MN USA. [Ancoli-Israel, S.] Univ Calif San Diego, San Diego, CA 92103 USA. [Redline, S.] Case Western Reserve Univ, Cleveland, OH 44106 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 37 EP 37 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006701179 ER PT J AU Laffan, A Stone, KL Blackwell, T Ancoli-Israel, S Ensrud, K Redline, S Slinin, Y Yaffe, K AF Laffan, A. Stone, K. L. Blackwell, T. Ancoli-Israel, S. Ensrud, K. Redline, S. Slinin, Y. Yaffe, K. TI SLEEP DURATION AND DISRUPTION: ASSOCIATIONS WITH COGNITIVE DECLINE IN OLDER MEN SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Laffan, A.; Stone, K. L.; Blackwell, T.] Calif Pacific Med Ctr, San Francisco, CA USA. [Yaffe, K.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Ancoli-Israel, S.] Univ Calif San Diego, San Diego, CA 92103 USA. [Yaffe, K.] San Francisco VA Med Ctr, San Francisco, CA USA. [Ensrud, K.; Slinin, Y.] Vet Affairs Med Ctr, Minneapolis, MN USA. [Redline, S.] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Ensrud, K.; Slinin, Y.] Univ Minnesota, Minneapolis, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 38 EP 38 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006701181 ER PT J AU Lee, CG Boyko, EJ Strotmeyer, ES Cawthon, PM Hoffman, AR Everson-Rose, S Barrett-Connor, E Orwoll, E AF Lee, C. G. Boyko, E. J. Strotmeyer, E. S. Cawthon, P. M. Hoffman, A. R. Everson-Rose, S. Barrett-Connor, E. Orwoll, E. TI INCREASED RISK OF LEAN MASS LOSS ASSOCIATED WITH INSULIN RESISTANCE IN OLDER MEN SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Lee, C. G.; Orwoll, E.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Boyko, E. J.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. [Strotmeyer, E. S.] Univ Pittsburgh, Pittsburgh, PA USA. [Cawthon, P. M.] Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA. [Hoffman, A. R.] Stanford Sch Med, Palo Alto, CA USA. [Everson-Rose, S.] Univ Minnesota, Minneapolis, MN USA. [Barrett-Connor, E.] Univ Calif San Diego, San Diego, CA 92103 USA. RI Strotmeyer, Elsa/F-3015-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 41 EP 41 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006701195 ER PT J AU Shrestha, S Bradford, A Snow, A Wilson, N Stanley, M Kunik, ME AF Shrestha, S. Bradford, A. Snow, A. Wilson, N. Stanley, M. Kunik, M. E. TI PREVENTING AGGRESSION IN VETERANS WITH DEMENTIA SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Shrestha, S.; Bradford, A.; Wilson, N.; Stanley, M.; Kunik, M. E.] Baylor Coll Med, Houston Ctr Qual Care & Utilizat Studies, Houston, TX 77030 USA. [Stanley, M.; Kunik, M. E.] Michael E Debakey Vet Affair Med Ctr, Houston, TX USA. [Snow, A.] Univ Alabama, Tuscaloosa, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 66 EP 66 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006701315 ER PT J AU Azar, AR Chopra, MP Rudolph, J AF Azar, A. R. Chopra, M. P. Rudolph, J. TI COMORBID ANXIETY IN OLDER PRIMARY CARE PATIENTS WITH MAJOR DEPRESSION: EFFECTS OF VASCULAR RISK SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Azar, A. R.; Chopra, M. P.; Rudolph, J.] VA Boston Healthcare Syst, Brockton, MA USA. [Chopra, M. P.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Chopra, M. P.; Rudolph, J.] Harvard Univ, Sch Med, Boston, MA USA. [Rudolph, J.] Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 104 EP 105 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006701499 ER PT J AU Jones, C Spiro, A Aldwin, CM AF Jones, C. Spiro, A. Aldwin, C. M. TI PATHWAYS OF PHYSICAL AND MENTAL HEALTH IN OLD AGE: LONGITUDINAL FINDINGS FROM THE IGS AND THE NAS SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Jones, C.] Calif State Univ Fresno, Fresno, CA 93740 USA. [Spiro, A.] VA Boston Healthcare Syst, Boston, MA USA. [Aldwin, C. M.] Oregon State Univ, Corvallis, OR 97331 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 113 EP 113 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006701540 ER PT J AU Karel, M Holley, C Whitbourne, SK Segal, DL AF Karel, M. Holley, C. Whitbourne, S. K. Segal, D. L. TI PRELIMINARY VALIDATION OF A PROFESSIONAL GEROPSYCHOLOGY COMPETENCIES ASSESSMENT TOOL SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Segal, D. L.] Univ Colorado, Colorado Springs, CO 80907 USA. [Karel, M.] VA Boston Healthcare Syst, Psychol Serv, Brockton, MA USA. [Holley, C.] Stratton VA Med Ctr, Albany, NY USA. [Whitbourne, S. K.] Univ Massachusetts, Amherst, MA 01003 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 113 EP 113 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006701538 ER PT J AU Ahluwalia, S Leos, R Goebel, JR Lorenz, K AF Ahluwalia, S. Leos, R. Goebel, J. R. Lorenz, K. TI A USER-CENTERED DESIGN APPROACH TO THE DEVELOPMENT OF A CLINICAL INFORMATICS SYMPTOM ASSESSMENT TOOL SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Ahluwalia, S.; Leos, R.; Goebel, J. R.; Lorenz, K.] Vet Adm Greater Los Angeles, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 132 EP 132 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006701630 ER PT J AU Tsukuda, R AF Tsukuda, R. TI INTERDISCIPLINARY TEAMWORK: LESSONS HISTORY CAN TEACH US FOR THE FUTURE SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Tsukuda, R.] Portland VA Med Ctr, Portland, OR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 141 EP 141 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006701674 ER PT J AU Menon, S McCullough, LB Espadas, D Braun, U AF Menon, S. McCullough, L. B. Espadas, D. Braun, U. TI FEASIBILITY OF USING A VALUES INVENTORY AS A DISCUSSION AID ABOUT END-OF-LIFE CARE SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Menon, S.; McCullough, L. B.; Espadas, D.; Braun, U.] VA Med Ctr, Houston Ctr Qual Care & Utilizat Studies, Houston, TX USA. [Braun, U.] Baylor Coll Med, Dept Med, Sect Geriatr, Houston, TX 77030 USA. [McCullough, L. B.; Braun, U.] Baylor Coll Med, Ctr Eth & Hlth Policy, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 211 EP 211 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006702131 ER PT J AU Espinoza, SE Hazuda, HP AF Espinoza, S. E. Hazuda, H. P. TI FRAILTY IN MEXICAN AMERICANS: WHERE THEY LIVE MAKES A DIFFERENCE SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Espinoza, S. E.] Univ Texas Hlth Sci Ctr San Antonio, Div Geriatr & Gerontol, San Antonio, TX 78229 USA. [Hazuda, H. P.] Univ Texas Hlth Sci Ctr San Antonio Med, Div Clin Epidemiol, San Antonio, TX USA. [Espinoza, S. E.; Hazuda, H. P.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 212 EP 213 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006702137 ER PT J AU Espinoza, SE Pierce, A Halade, D Richardson, A AF Espinoza, S. E. Pierce, A. Halade, D. Richardson, A. TI PLASMA HAPTOGLOBIN IN PRE-FRAIL OLDER ADULTS: A PILOT STUDY SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Espinoza, S. E.; Pierce, A.; Halade, D.; Richardson, A.] Univ Texas Hlth Sci Ctr San Antonio, Barshop Inst Longev & Aging Studies, San Antonio, TX 78229 USA. [Espinoza, S. E.; Pierce, A.; Halade, D.; Richardson, A.] S Texas Vet Hlth Care Syst, San Antonio, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 213 EP 213 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006702138 ER PT J AU Ahluwalia, S Gross, CP Chaudhry, S Fried, TR AF Ahluwalia, S. Gross, C. P. Chaudhry, S. Fried, T. R. TI THE IMPACT OF COMORBIDITY ON MORTALITY AMONG OLDER PERSONS WITH ADVANCED HEART FAILURE SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Ahluwalia, S.] Vet Adm Greater Los Angeles, Los Angeles, CA USA. [Gross, C. P.; Chaudhry, S.; Fried, T. R.] Yale Univ, New Haven, CT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 215 EP 215 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006702147 ER PT J AU Hutt, E Ho, M Pointer, L Shahan, E AF Hutt, E. Ho, M. Pointer, L. Shahan, E. TI EFFECTIVENESS OF ACEI/ARBS IN VA NURSING HOME RESIDENTS WITH HEART FAILURE SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Hutt, E.; Ho, M.; Pointer, L.; Shahan, E.] Univ Colorado, Denver VAMC, Denver, CO 80202 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 215 EP 215 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006702148 ER PT J AU Ahluwalia, S Gross, CP Chaudhry, S Fried, TR AF Ahluwalia, S. Gross, C. P. Chaudhry, S. Fried, T. R. TI A LONGITUDINAL ANALYSIS OF COMORBIDITY BURDEN AMONG OLDER ADULTS WITH HEART FAILURE SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Ahluwalia, S.] Vet Adm Greater Los Angeles, Los Angeles, CA USA. [Gross, C. P.; Chaudhry, S.; Fried, T. R.] Yale Univ, New Haven, CT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 216 EP 216 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006702150 ER PT J AU Griffith, JL AF Griffith, J. L. TI SOCIAL SUPPORT AND SEXUAL INTEREST IN OLDER ADULTHOOD: A PROFILE FROM THE NATIONAL SOCIAL LIFE, HEALTH AND AGING PROJECT (NSHAP) SO GERONTOLOGIST LA English DT Meeting Abstract C1 Mt Sinai Sch Med, Dept Geriatr & Palliat Med, New York, NY USA. Ctr Geriatr Res Educ & Clin, James J Peters VA Med Ctr, Bronx, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 240 EP 241 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006702273 ER PT J AU Lane, D AF Lane, D. TI "POINTS TO CONSIDER IN PLANNING FOR A SUCCESSFUL CAREER PROVIDING PSYCHOLOGICAL CARE TO OLDER ADULTS" SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Lane, D.] VA Puget Sound Healthcare Syst, Geriatr & Extended Care Serv, Tacoma, WA USA. [Lane, D.] Univ Washington, Sch Med, Dept Psychiat, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 243 EP 243 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006702285 ER PT J AU Ayotte, BJ Patrick, JH Goedereis, E Stahl, S AF Ayotte, B. J. Patrick, J. H. Goedereis, E. Stahl, S. TI FUTURE TIME PERSPECTIVE, HEALTH LOCUS OF CONTROL, AND HEALTH BEHAVIORS: THE MEDIATING ROLE OF AFFECT SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Ayotte, B. J.] VA Boston Healthcare Syst, Boston, MA USA. [Patrick, J. H.; Stahl, S.] W Virginia Univ, Morgantown, WV 26506 USA. [Goedereis, E.] Webster Univ, St Louis, MO USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 281 EP 281 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006702467 ER PT J AU Hilgeman, MM Durkin, DW Harris, G Haley, PP Allen, RS AF Hilgeman, M. M. Durkin, D. W. Harris, G. Haley, P. P. Allen, R. S. TI PRESERVING IDENTITY IN THE EARLY STAGES OF DEMENTIA: FEASIBILITY OF A BRIEF REMINISCENCE-BASED INTERVENTION SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Hilgeman, M. M.; Durkin, D. W.; Harris, G.; Haley, P. P.; Allen, R. S.] Univ Alabama, Tuscaloosa, AL USA. [Hilgeman, M. M.] VA Boston Healthcare Syst, Boston, MA USA. [Hilgeman, M. M.; Durkin, D. W.; Harris, G.; Haley, P. P.; Allen, R. S.] Ctr Mental Hlth & Aging, Tuscaloosa, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 309 EP 309 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006702602 ER PT J AU Bass, DM Looman, WJ McCarthy, C Walder, A Morgan, RO AF Bass, D. M. Looman, W. J. McCarthy, C. Walder, A. Morgan, R. O. TI OUTCOMES FOR CAREGIVERS AFTER SIX-MONTHS IN PARTNERS IN DEMENTIA CARE SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Bass, D. M.; Looman, W. J.; McCarthy, C.] Benjamin Rose Inst, Margaret Blenkner Res Inst, Cleveland, OH USA. [Walder, A.] Michael E DeBakey Vet Med Ctr, Houston, TX USA. [Morgan, R. O.] Univ Texas Houston, Sch Publ Hlth, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 322 EP 323 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006702661 ER PT J AU Turiano, NA Spiro, A Mroczek, D AF Turiano, N. A. Spiro, A. Mroczek, D. TI FACETS OF CONSCIENTIOUSNESS AS PREDICTORS OF MORTALITY SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Turiano, N. A.; Mroczek, D.] Purdue Univ, W Lafayette, IN 47907 USA. [Turiano, N. A.; Mroczek, D.] Ctr Aging, W Lafayette, IN USA. [Turiano, N. A.; Mroczek, D.] Life Course, W Lafayette, IN USA. [Spiro, A.] VA Boston Healthcare Syst, Normat Aging Study, Boston, MA USA. [Spiro, A.] Boston Univ, Sch Publ Hlth, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 323 EP 323 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006702665 ER PT J AU Kramer, B AF Kramer, B. TI THE GERIATRIC SCHOLARS PROGRAM: AN OVERVIEW SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Kramer, B.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Kramer, B.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 341 EP 341 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006702747 ER PT J AU Adamson, MM Weinstein, H Cherrier, M Diep, H Taylor, J AF Adamson, M. M. Weinstein, H. Cherrier, M. Diep, H. Taylor, J. TI SPATIAL NAVIGATION ABILITIES IN OLDER PILOTS AND NON-PILOTS SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Adamson, M. M.; Weinstein, H.; Diep, H.; Taylor, J.] VA Palo Alto Hlth Care Syst, Palo Alto, CA USA. [Cherrier, M.] VA Puget Sound Hlth Care Syst, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 355 EP 355 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006702813 ER PT J AU Goedereis, E Patrick, JH Ayotte, B AF Goedereis, E. Patrick, J. H. Ayotte, B. TI DAILY CHANGES AMONG PHYSICAL ACTIVITY GOAL PROCESSES AND SUBJECTIVE WELL-BEING DURING MIDLIFE SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Goedereis, E.] Webster Univ, St Louis, MO USA. [Patrick, J. H.] W Virginia Univ, Morgantown, WV 26506 USA. [Ayotte, B.] VA Boston Healthcare Syst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 362 EP 362 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006702851 ER PT J AU Hilgeman, MM Allen, RS Miller, L Rhodes, J Magnuson, R Turgeon, C AF Hilgeman, M. M. Allen, R. S. Miller, L. Rhodes, J. Magnuson, R. Turgeon, C. TI COPING AND VALUES IN MILD DEMENTIA: PILOT DATA FROM A NEW PATIENT-CENTERED INTERVENTION SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Hilgeman, M. M.; Allen, R. S.; Miller, L.; Rhodes, J.; Magnuson, R.; Turgeon, C.] Univ Alabama, Tuscaloosa, AL USA. [Hilgeman, M. M.; Allen, R. S.; Miller, L.] Ctr Mental Hlth & Aging, Tuscaloosa, AL USA. [Hilgeman, M. M.] VA Boston Healthcare Syst, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 367 EP 367 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006702877 ER PT J AU Alessi, C AF Alessi, C. TI HS PRESIDENTIAL SYMPOSIUM: CHANGES IN LATITUDES, CHANGES IN ATTITUDES: TRANSITIONS OF CARE IN TIMES OF DISASTER AND POVERTY SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Alessi, C.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Alessi, C.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 368 EP 368 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006703003 ER PT J AU Bates-Jensen, B AF Bates-Jensen, B. TI WOUND CARE IN HAITI 1 MONTH POST EARTHQUAKE: INFECTION, REPAIR, AND REHABILITATION SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Bates-Jensen, B.] Univ Calif Los Angeles, Sch Nursing, Los Angeles, CA 90024 USA. [Bates-Jensen, B.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 368 EP 368 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006703005 ER PT J AU Kramer, B AF Kramer, B. TI INSTEP (INCREASING STABILITY THROUGH EVALUATION AND PRACTICE): PROCESS EVALUATION SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Kramer, B.] VA Greater Los Angeles Healthcare Syst, GRECC, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 385 EP 385 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006703083 ER PT J AU Rubenstein, L Kramer, B Vivrette, R AF Rubenstein, L. Kramer, B. Vivrette, R. TI STAYING INDEPENDENT: VALIDATING A FALL RISK SCREENER SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Rubenstein, L.; Kramer, B.; Vivrette, R.] VA Greater Los Angeles Healthcare Syst, GRECC, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 385 EP 385 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006703085 ER PT J AU Rubenstein, L AF Rubenstein, L. TI INSTEP (INCREASING STABILITY THROUGH EVALUATION AND PRACTICE): OUTCOME ANALYSIS SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Rubenstein, L.] VA Greater Los Angeles Healthcare Syst, GRECC, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 385 EP 385 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006703084 ER PT J AU Payne, KL AF Payne, K. L. TI TIPS, TRICKS, AND ADVICE FOR LANDING A POSTDOCTORAL FELLOWSHIP IN GEROPSYCHOLOGY SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Payne, K. L.] Milwaukee VA, Milwaukee, WI USA. [Payne, K. L.] Portland VA Med Ctr, Portland, OR USA. [Payne, K. L.] Univ Alabama, Tuscaloosa, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 394 EP 394 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006703129 ER PT J AU Gray, DA Henderson, DC Harris, BL Boxill, R Carney, JR Borba, C AF Gray, D. A. Henderson, D. C. Harris, B. L. Boxill, R. Carney, J. R. Borba, C. TI UNDERSTANDING COHORT DIFFERENCES IN APPRAISALS OF RECONSTRUCTION PRIORITIES OF MENTAL HEALTH SYSTEMS IN POST-CONFLICT LIBERIA SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Gray, D. A.] Univ Massachusetts, Boston, MA 02125 USA. [Gray, D. A.; Henderson, D. C.; Boxill, R.; Carney, J. R.; Borba, C.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Harris, B. L.] Univ Liberia, Monrovia, LA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 409 EP 409 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006703201 ER PT J AU Brady, CB Spiro, A AF Brady, C. B. Spiro, A. TI DEMENTIA AND POSTTRAUMATIC STRESS DISORDER IN OLDER ADULTS: NEUROPSYCHOLOGICAL PERSPECTIVES SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Brady, C. B.; Spiro, A.] VA Boston Healthcare Syst, Boston, MA USA. [Brady, C. B.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Spiro, A.] Boston Univ, Sch Publ Hlth, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 434 EP 435 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006703325 ER PT J AU Alessi, C Martin, J Fiorentino, L Chung, C Josephson, K Jouldjian, S AF Alessi, C. Martin, J. Fiorentino, L. Chung, C. Josephson, K. Jouldjian, S. TI DEVELOPMENT OF A NONPHARMACOLOGICAL INTERVENTION TO IMPROVE SLEEP PATTERNS AMONG OLDER ADULTS UNDERGOING INPATIENT POST-ACUTE REHABILITATION SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Alessi, C.; Martin, J.; Josephson, K.; Jouldjian, S.] VA Greater Angeles Healthcare Syst, Los Angeles, CA USA. [Alessi, C.; Martin, J.; Fiorentino, L.; Chung, C.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 482 EP 482 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006703551 ER PT J AU Byers, AL Arean, PA Yaffe, K AF Byers, A. L. Arean, P. A. Yaffe, K. TI PREVALENCE AND CHARACTERISTICS OF MENTAL HEALTH SERVICES USE IN OLDER AMERICANS WITH AND WITHOUT MOOD AND ANXIETY DISORDERS SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Byers, A. L.; Arean, P. A.; Yaffe, K.] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. [Byers, A. L.; Yaffe, K.] San Francisco VA Med Ctr, San Francisco, CA USA. [Yaffe, K.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. [Yaffe, K.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 496 EP 496 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006703619 ER PT J AU Moreno, G Mangione, CM Wang, P Trejo, L Butch, A Sarkisian, C AF Moreno, G. Mangione, C. M. Wang, P. Trejo, L. Butch, A. Sarkisian, C. TI ARE PHYSICAL ACTIVITY AND PHYSICAL PERFORMANCE ASSOCIATED WITH BIO-MARKERS AMONG ELDERLY LATINOS? SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Moreno, G.] UCLA Dept Family Med, Los Angeles, CA USA. [Mangione, C. M.] UCLA Dept Med, Div Gen Internal Med & Hlth Serv, Los Angeles, CA USA. [Mangione, C. M.; Wang, P.; Sarkisian, C.] UCLA Dept Med, Div Geriatr, Los Angeles, CA USA. [Trejo, L.] Dept Aging, Los Angeles, CA USA. [Butch, A.] UCLA Pathol Lab Med, Los Angeles, CA USA. [Sarkisian, C.] VA Greater Healthcare Syst, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 517 EP 517 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006703711 ER PT J AU Chodosh, J Miller-Martinez, D Aneshensel, C Wight, RG Karlamangla, AS AF Chodosh, J. Miller-Martinez, D. Aneshensel, C. Wight, R. G. Karlamangla, A. S. TI DEPRESSIVE SYMPTOMS, CHRONIC DISEASE, AND PHYSICAL DISABILITY AS PREDICTORS OF COGNITIVE FUNCTIONING SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Chodosh, J.; Miller-Martinez, D.; Karlamangla, A. S.] UCLA Div Geriatr, Los Angeles, CA USA. [Chodosh, J.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Aneshensel, C.; Wight, R. G.] Community Hlth Sci UCLA, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 525 EP 526 PG 2 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006703747 ER PT J AU Trevino, K Archambault, E Hilgeman, MM Billings, RL Gosian, J Schuster, J Moye, J AF Trevino, K. Archambault, E. Hilgeman, M. M. Billings, R. L. Gosian, J. Schuster, J. Moye, J. TI RELIGION AND SPIRITUALITY IN VETERAN CANCER SURVIVORS: A QUALITATIVE PERSPECTIVE SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Trevino, K.; Archambault, E.; Hilgeman, M. M.; Billings, R. L.; Gosian, J.; Schuster, J.; Moye, J.] VA Boston Healthcare Syst, Brockton, MA USA. [Trevino, K.; Hilgeman, M. M.; Billings, R. L.; Moye, J.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2010 VL 50 SU 1 BP 539 EP 539 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 703UL UT WOS:000286006703809 ER PT J AU Gallun, FJ Saunders, GH AF Gallun, Frederick J. Saunders, Gabrielle H. TI The Ear-Brain System: Approaches to the Study and Treatment of Hearing Loss SO JOURNAL OF THE AMERICAN ACADEMY OF AUDIOLOGY LA English DT Editorial Material ID SPECTRAL SHAPE-DISCRIMINATION; LISTENERS; ADULTS; SPEECH; NOISE C1 [Gallun, Frederick J.; Saunders, Gabrielle H.] Rehabil Res & Dev Serv RR&D, US Dept Vet Affairs, Natl Ctr Rehabil Auditory Res, Portland, OR 97239 USA. RP Gallun, FJ (reprint author), Rehabil Res & Dev Serv RR&D, US Dept Vet Affairs, Natl Ctr Rehabil Auditory Res, 3710 SW US Vet Hosp Rd, Portland, OR 97239 USA. RI Gallun, Frederick/G-3792-2012 OI Gallun, Frederick/0000-0002-4145-2199 NR 12 TC 0 Z9 0 U1 1 U2 2 PU AMER ACAD AUDIOLOGY PI RESTON PA 11730 PLAZA DR, STE 300, RESTON, VA 20190 USA SN 1050-0545 J9 J AM ACAD AUDIOL JI J. Am. Acad. Audiol. PD OCT PY 2010 VL 21 IS 9 SI SI DI 10.3766/jaaa.21.9.1 PG 3 WC Audiology & Speech-Language Pathology; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Otorhinolaryngology GA 704YF UT WOS:000286090900001 ER PT J AU Barisoni, L Jennette, CJ Colvin, RB Boudes, P Sitaraman, S Castelli, J Bragat, A AF Barisoni, L. Jennette, C. J. Colvin, R. B. Boudes, P. Sitaraman, S. Castelli, J. Bragat, A. TI Novel quantitative virtual microscopy-based method to evaluate GL-3 inclusions in renal peritubular capillaries in patients with fabry disease SO HISTOPATHOLOGY LA English DT Meeting Abstract CT 28th International Congress of the International-Academy-of-Pathology CY OCT 10-15, 2010 CL Sao Paulo, BRAZIL SP Int Acad Pathol C1 [Barisoni, L.] NYU, Sch Med, Dept Pathol, New York, NY USA. [Jennette, C. J.] Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC USA. [Colvin, R. B.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Boudes, P.; Sitaraman, S.; Castelli, J.; Bragat, A.] Amicus Therapeut, Cranbury, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0309-0167 J9 HISTOPATHOLOGY JI Histopathology PD OCT PY 2010 VL 57 SU 1 MA 665 BP 239 EP 239 PG 1 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 656GW UT WOS:000282317400663 ER PT J AU Smolderen, KG Bell, A Lei, Y Cohen, EA Steg, PG Bhatt, DL Mahoney, EM AF Smolderen, Kim G. Bell, Alan Lei, Yang Cohen, Eric A. Steg, P. Gabriel Bhatt, Deepak L. Mahoney, Elizabeth M. CA REACH Registry Investigators TI One-year costs associated with cardiovascular disease in Canada: Insights from the REduction of Atherothrombosis for Continued Health (REACH) registry SO CANADIAN JOURNAL OF CARDIOLOGY LA English DT Article DE Cerebrovascular disease; Coronary disease; Costs; Hospitalization; Peripheral vascular disease ID PERIPHERAL ARTERIAL-DISEASE; HEART-FAILURE; RISK-FACTORS; OUTPATIENTS; TRENDS; AWARENESS; BURDEN; STROKE; IMPACT; RATES AB BACKGROUND And OBJECTIVES: To provide a contemporary estimate of the economic burden of atherothrombosis in Canada, annual cardiovascular-related hospitalizations, medication use and associated costs across the entire spectrum of atherothrombotic disease were examined. METHODS: The REduction of Atherothrombosis for Continued Health (REACH) registry enrolled 1964 Canadian outpatients with coronary artery disease, cerebrovascular disease or peripheral arterial disease (PAD), or three or more cardiovascular risk factors. Baseline data on cardiovascular risk factors and associated medication use, and one-year follow-up data on cardiovascular events, hospitalizations, procedures and medication use were collected. Annual hospitalization and medication costs (Canadian dollars) were derived and compared among patients according to the presence of established atherothrombotic disease at baseline, specific arterial beds affected and the number of affected arterial beds. RESULTS: Average annualized medication costs were $ 1,683, $ 1,523 and $ 1,776 for patients with zero, one, and two or three symptomatic arterial beds, respectively. Average annual hospitalization costs increased significantly with the number of beds affected ($ 380, $ 1,403 and $ 3,465, respectively; P<0.0001 for overall linear trend). Mean hospitalization costs for patients with any coronary artery disease, any cerebrovascular disease and any PAD were $ 1,743, $ 1,823 and $ 4,677, respectively. After adjusting for other clinical factors, PAD at baseline was independently associated with a significant increase in hospitalization costs. CONCLUSION: Costs associated with vascular-related hospitalizations and interventions for Canadian patients increased with the number of affected arterial beds, and were particularly high for patients with PAD and/or polyvascular disease. These contemporary data provide insight into the economic burden associated with atherothrombotic disease in Canada, and highlight the need for increased preventive strategies to lessen the burden for patients and society. C1 [Smolderen, Kim G.; Lei, Yang; Mahoney, Elizabeth M.] St Lukes Hosp, Mid Amer Heart Inst, Kansas City, MO 64111 USA. [Smolderen, Kim G.] Tilburg Univ, Dept Med Psychol, Ctr Res Psychol Somat Dis, NL-5000 LE Tilburg, Netherlands. [Bell, Alan] Univ Toronto, Toronto, ON M5S 1A1, Canada. [Cohen, Eric A.] Sunnybrook Hlth Sci Ctr, Schulich Heart Ctr, Toronto, ON M4N 3M5, Canada. [Steg, P. Gabriel] Hop Bichat Claude Bernard, F-75877 Paris 18, France. [Bhatt, Deepak L.] VA Boston Healthcare Syst, Boston, MA USA. [Bhatt, Deepak L.] Brigham & Womens Hosp, Boston, MA 02115 USA. RP Mahoney, EM (reprint author), St Lukes Hosp, Mid Amer Heart Inst, 4401 Wornall Rd, Kansas City, MO 64111 USA. EM emahoney1@saint-lukes.org RI Smolderen, Kim/B-8078-2015 FU Bristol-Myers Squibb (USA); Sanofi-aventis (France); Waksman Foundation (Japan); American Heart Association Pharmaceutical Roundtable; Pfizer (Canada); Sanofi-aventis (Canada); AstraZeneca (Canada); Bristol-Myers Squibb (Canada); Novartis (Canada); Bayer (Canada); Boehringer Ingelheim (Canada); Servier (France); AstraZeneca (Sweden); Eisai (Japan); Medicines Company (USA); Daiichi-Sankyo (USA); Eli Lilly (USA) FX The REACH registry was sponsored by a grant from Bristol-Myers Squibb (USA), sanofi-aventis (France) and the Waksman Foundation (Japan). The REACH registry is endorsed by the World Heart Federation. A complete list of REACH investigators is accessible online at www.reachregistry.org. The REACH registry enforces a no ghost-writing policy. This manuscript was written and edited by the authors, who take full responsibility for its content. The first draft was written by Dr Smolderen. Dr Smolderen was supported by an award from the American Heart Association Pharmaceutical Roundtable, and David and Stevie Spina.; Dr Smolderen has no disclosures. Dr Bell has received research grants and/or speakers honoraria from the following organizations: Pfizer (Canada), sanofi-aventis (Canada), AstraZeneca (Canada), Bristol-Myers Squibb (Canada), Novartis (Canada), Bayer (Canada) and Boehringer Ingelheim (Canada). Ms Lei has no disclosures. Dr Cohen has received research grants from sanofi-aventis (Canada), Novartis (Canada) and AstraZeneca (Canada); speaker's honoraria from sanofi-aventis (Canada), Bristol-Myers Squibb (Canada) and AstraZeneca (Canada); and consulting fees from sanofi-aventis (Canada) and AstraZeneca (Canada). Dr Steg has received research grant support from Servier (France; 2009 to 2014); is a consultant or advisory board member for Astellas (Netherlands), AstraZeneca (Sweden), Bayer (France), Boehringer Ingelheim (France), BMS (France), Daiichi-Sankyo-Lilly (France), GlaxoSmithKline (France), Medtronic (Netherlands), Otsuka (USA), Roche (Switzerland), sanofi-aventis (France), Servier (France) and The Medicines Company (France); and is a stockholder for Aterovax (France). Dr Bhatt has received institutional research funding from AstraZeneca (Sweden), Bristol-Myers Squibb (USA), Eisai (Japan), sanofi-aventis (France) and The Medicines Company (USA). Dr Mahoney has received grant support from sanofi-aventis (France), sanofi-aventis (Canada), Bristol-Myers Squibb (USA), Daiichi-Sankyo (USA) and Eli Lilly (USA), and has received honoraria from sanofi-aventis (France), Bristol-Myers Squibb (USA) and Bristol-Myers Squibb (Canada). NR 35 TC 3 Z9 3 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0828-282X J9 CAN J CARDIOL JI Can. J. Cardiol. PD OCT PY 2010 VL 26 IS 8 BP E297 EP E305 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 676PE UT WOS:000283923700002 ER PT J AU Zuleger, CL Macklin, MD Newton, MA Albertini, MR AF Zuleger, Cindy L. Macklin, Michael D. Newton, Michael A. Albertini, Mark R. TI In Vivo 6-thioguanine-resistant T Cells from Melanoma Patients Contain T Cells with Melanoma Specificity as well as T Cells with Suppressive Function SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract C1 [Zuleger, Cindy L.; Macklin, Michael D.; Newton, Michael A.; Albertini, Mark R.] Univ Wisconsin, Sch Med & Publ Hlth, Carbone Comprehens Canc Ctr, Madison, WI 53706 USA. [Albertini, Mark R.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD OCT PY 2010 VL 33 IS 8 BP 889 EP 889 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 653XQ UT WOS:000282131800107 ER PT J AU Margolin, K Hamid, O McDermott, D Puzanov, I Sznol, M Clark, JI Wolchok, J Hodi, FS Heller, K Lawrence, D AF Margolin, K. Hamid, O. McDermott, D. Puzanov, I. Sznol, M. Clark, J. I. Wolchok, J. Hodi, F. S. Heller, K. Lawrence, D. TI Ipilimumab Monotherapy in Melanoma Patients with Brain Metastases-Update of a Phase II Study SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract C1 [Margolin, K.] Univ Washington, Seattle, WA 98195 USA. [Hamid, O.] Angeles Clin & Res Inst, Santa Monica, CA USA. [McDermott, D.] Beth Israel Deaconess Med Ctr, Boston, MA USA. [Hodi, F. S.] Dana Farber Canc Inst, Boston, MA USA. [Lawrence, D.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Puzanov, I.] Vanderbilt Ingram Canc Ctr, Nashville, TN USA. [Sznol, M.] Yale Canc Ctr, New Haven, CT USA. [Clark, J. I.] Loyola Univ, Med Ctr, Maywood, IL 60153 USA. [Wolchok, J.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Heller, K.] Bristol Myers Squibb Co, Plainsboro, NJ USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD OCT PY 2010 VL 33 IS 8 BP 903 EP 903 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 653XQ UT WOS:000282131800149 ER PT J AU McDermott, D Ghebremichael, M Signoretti, S Margolin, K Clark, J Sosman, J Dutcher, J Logan, T Appleman, L Atkins, M AF McDermott, D. Ghebremichael, M. Signoretti, S. Margolin, K. Clark, J. Sosman, J. Dutcher, J. Logan, T. Appleman, L. Atkins, M. TI The High-Dose Aldesleukin (HD IL-2) "Select'' Trial in Patients with Metastatic Renal Cell Carcinoma (mRCC) SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract C1 [McDermott, D.; Atkins, M.] Beth Israel Deaconess Med Ctr, Boston, MA USA. [Ghebremichael, M.; Signoretti, S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Margolin, K.] Univ Washington, Seattle, WA 98195 USA. [Clark, J.] Loyola Univ, Med Ctr, Chicago, IL 60611 USA. [Sosman, J.] Vanderbilt Univ, Med Ctr, Nashville, TN USA. [Dutcher, J.] Montefiore Med Ctr, New York, NY USA. [Logan, T.] Indiana Univ, Indianapolis, IN 46204 USA. [Appleman, L.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD OCT PY 2010 VL 33 IS 8 BP 903 EP 904 PG 2 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 653XQ UT WOS:000282131800151 ER PT J AU O'Day, SJ McDermott, DF Urba, WJ Wolchok, JD Robert, C Haanen, JB Dummer, R Messina, M Hoos, A Hodi, FS AF O'Day, Steven J. McDermott, David F. Urba, Walter J. Wolchok, Jedd D. Robert, Caroline Haanen, John B. Dummer, Reinhard Messina, Marianne Hoos, Axel Hodi, F. Stephen TI Ipilimumab Improves Overall Survival in Previously Treated, Advanced Melanoma Patients with Good and Poor Prognostic Factors SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract C1 [O'Day, Steven J.] Angeles Clin, Los Angeles, CA USA. [O'Day, Steven J.] Res Inst, Los Angeles, CA USA. [Hodi, F. Stephen] Dana Farber Canc Inst, Boston, MA 02115 USA. [Urba, Walter J.] Earle A Chiles Res Inst, Portland, OR USA. [Wolchok, Jedd D.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Robert, Caroline] Inst Gustave Roussy, Villejuif, France. [Haanen, John B.] Netherlands Canc Inst, Amsterdam, Netherlands. [Dummer, Reinhard] Univ Hosp, Zurich, Switzerland. [Messina, Marianne; Hoos, Axel] Bristol Myers Squibb Co, Wallingford, CT 06492 USA. [McDermott, David F.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD OCT PY 2010 VL 33 IS 8 BP 905 EP 906 PG 2 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 653XQ UT WOS:000282131800158 ER PT J AU Han, S James, M Ramesh, V AF Han, S. James, M. Ramesh, V TI COMMON PATHWAY IN UNCOMMON DISEASES; THE TSC/mTOR SIGNALING PATHWAY IN NEUROCUTANEOUS DISEASES SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 [Han, S.; James, M.; Ramesh, V] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD OCT PY 2010 VL 115 SU 1 BP 10 EP 11 PG 2 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 649YS UT WOS:000281812600022 ER PT J AU Miller, MW AF Miller, Mark W. TI On Comparing Competing Models of PTSD: Response to Simms SO JOURNAL OF TRAUMATIC STRESS LA English DT Editorial Material ID POSTTRAUMATIC-STRESS-DISORDER; CONFIRMATORY FACTOR-ANALYSIS; SYMPTOMS; VETERANS; EXPOSURE; STIMULI; STARTLE; SCALE; WOMEN; WAR AB This is a response to Simms' commentary on Miller, Wolf Harrington, Brown, Kaloupek, and Keane (2010) comparing the convergent and discriminant validity of two 4-factor models of posttraumatic stress disorder (PTSD) using external measures of comorbidity. The author reviews the importance of the distinction between numbing and hyperarousal, clarifies the logic and rationale for the study's aims and hypotheses, and responds to specific concerns about the conclusions. He addresses the relationship between hyperarousal symptoms and internalizing comorbidity and notes the limitations of representing the latter construct using only two symptoms. The author concludes by underscoring the need for future research to place greater emphasis on examining the external correlates of alternative models of the factor structure of PTSD. C1 [Miller, Mark W.] VA Boston Healthcare Syst, VA Natl Ctr PTSD, Boston, MA 02130 USA. [Miller, Mark W.] Boston Univ, Sch Med, Div Psychiat, Boston, MA 02215 USA. RP Miller, MW (reprint author), VA Boston Healthcare Syst, VA Natl Ctr PTSD, 150 S Huntington Ave 116B-2, Boston, MA 02130 USA. EM mark.miller5@va.gov RI Miller, Mark/G-7322-2011 OI Miller, Mark/0000-0001-6393-8563 NR 27 TC 3 Z9 3 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0894-9867 J9 J TRAUMA STRESS JI J. Trauma Stress PD OCT PY 2010 VL 23 IS 5 BP 642 EP 644 DI 10.1002/jts.20561 PG 3 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 674PF UT WOS:000283758900013 ER PT J AU Aggarwal, S Zinman, L Schoenfeld, D Shefner, J Cudkowicz, M AF Aggarwal, Swati Zinman, Lorne Schoenfeld, David Shefner, Jeremy Cudkowicz, Merit TI Would riluzole be efficacious in the new ALS trial design? reply SO LANCET NEUROLOGY LA English DT Letter ID AMYOTROPHIC-LATERAL-SCLEROSIS; LITHIUM; PROGRESSION C1 [Zinman, Lorne] Sunnybrook Hlth Sci Ctr, Toronto, ON M4N 3M5, Canada. [Schoenfeld, David] Massachusetts Gen Hosp, Dept Biostat, Charlestown, MA USA. [Shefner, Jeremy] SUNY Upstate Med Univ, Syracuse, NY USA. [Cudkowicz, Merit] Massachusetts Gen Hosp, Neurol Clin Trials Unit, Charlestown, MA USA. RP Aggarwal, S (reprint author), B-2 Adishwar Apartments, Ahmadabad 380063, Gujarat, India. EM swatihshah@gmail.com NR 9 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 1474-4422 J9 LANCET NEUROL JI Lancet Neurol. PD OCT PY 2010 VL 9 IS 10 BP 950 EP 951 DI 10.1016/S1474-4422(10)70231-3 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 672WC UT WOS:000283616700009 ER PT J AU Levine, AC Shah, SP Umulisa, I Munyaneza, RBM Dushimiyimana, JM Stegmann, K Musavuli, J Ngabitsinze, P Stulac, S Epino, HM Noble, VE AF Levine, Adam C. Shah, Sachita P. Umulisa, Irenee Munyaneza, Richard B. Mark Dushimiyimana, Jean Marie Stegmann, Katrina Musavuli, Juvenal Ngabitsinze, Protogene Stulac, Sara Epino, Henry M. Noble, Vicki E. TI Ultrasound Assessment of Severe Dehydration in Children With Diarrhea and Vomiting SO ACADEMIC EMERGENCY MEDICINE LA English DT Article; Proceedings Paper CT American-College-of-Emergency-Physicians Scientific Assembly CY JAN 29, 2010 CL Boston, MA SP Amer Coll Emergency Phys DE gastroenteritis; diarrhea; pediatrics; dehydration; ultrasonography ID VENA-CAVA DIAMETER AB Objectives: The objective of this study was to determine the test characteristics for two different ultrasound (US) measures of severe dehydration in children (aorta to inferior vena cava [IVC] ratio and IVC inspiratory collapse) and one clinical measure of severe dehydration (the World Health Organization [WHO] dehydration scale). Methods: The authors enrolled a prospective cohort of children presenting with diarrhea and/or vomiting to three rural Rwandan hospitals. Children were assessed clinically using the WHO scale and then underwent US of the IVC by a second clinician. All children were weighed on admission and then fluid-resuscitated according to standard hospital protocols. A percent weight change between admission and discharge of greater than 10% was considered the criterion standard for severe dehydration. Receiver operating characteristic (ROC) curves were created for each of the three tests of severe dehydration compared to the criterion standard. Results: Children ranged in age from 1 month to 10 years; 29% of the children had severe dehydration according to the criterion standard. Of the three different measures of dehydration tested, only US assessment of the aorta/IVC ratio had an area under the ROC curve statistically different from the reference line. At its best cut-point, the aorta/IVC ratio had a sensitivity of 93% and specificity of 59%, compared with 93% and 35% for IVC inspiratory collapse and 73% and 43% for the WHO scale. Conclusions: Ultrasound of the aorta/IVC ratio can be used to identify severe dehydration in children presenting with acute diarrhea and may be helpful in guiding clinical management. ACADEMIC EMERGENCY MEDICINE 2010; 17:1035-1041 (C) 2010 by the Society for Academic Emergency Medicine. C1 [Levine, Adam C.; Shah, Sachita P.] Brown Univ, Alpert Med Sch, Dept Emergency Med, Providence, RI 02912 USA. [Noble, Vicki E.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Levine, AC (reprint author), Brown Univ, Alpert Med Sch, Dept Emergency Med, Providence, RI 02912 USA. EM adam_levine@brown.edu OI Levine, Adam/0000-0003-3982-3824 NR 16 TC 24 Z9 24 U1 2 U2 9 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD OCT PY 2010 VL 17 IS 10 BP 1035 EP 1041 DI 10.1111/j.1553-2712.2010.00830.x PG 7 WC Emergency Medicine SC Emergency Medicine GA 663IR UT WOS:000282877400002 PM 21040103 ER PT J AU Fernandez, R Wang, E Vozenilek, JA Hayden, E McLaughlin, S Godwin, SA Griswold-Theodorson, S Davenport, M Gordon, JA AF Fernandez, Rosemarie Wang, Ernest Vozenilek, John A. Hayden, Emily McLaughlin, Steve Godwin, Steven A. Griswold-Theodorson, Sharon Davenport, Moira Gordon, James A. CA SAEM Technology Med Educ Comm TI Simulation Center Accreditation and Programmatic Benchmarks: A Review for Emergency Medicine SO ACADEMIC EMERGENCY MEDICINE LA English DT Review DE simulation; accreditation; standards; medical education ID EDUCATION AB Simulation-based education has grown significantly over the past 10 years. As a result, more professional organizations are developing or implementing accreditation processes to help define minimum standards and best practices in simulation-based training. However, the benefits and potential pitfalls of sponsoring and implementing such programs have yet to be fully evaluated across specialties. The board of directors of the Society for Academic Emergency Medicine (SAEM) requested an evaluation of the potential to create an emergency medicine (EM)-based Simulation Consultation and Accreditation Service. In response to this request, the Simulation Accreditation and Consultation Work Group, a subgroup of the Committee on Technology in Medical Education (now Simulation Academy), was created. The work group was charged with: 1) reviewing current benchmarks and standards set by existing simulation accreditation programs; 2) analyzing current EM simulation program structures, including leadership, administrative, and financial components; and 3) proposing a potential model for EM-based simulation accreditation. This article outlines currently existing and proposed accreditation models and identifies components that support best practices. It then goes on to describe three general programmatic models to better understand how simulation training can be operationalized in EM. Finally, the work group uses this collective information to propose how an accreditation process, in concert with the SAEM Simulation Consultation Service, can enhance and advance EM simulation training. ACADEMIC EMERGENCY MEDICINE 2010; 17:1093-1103 (C) 2010 by the Society for Academic Emergency Medicine. C1 [Fernandez, Rosemarie] Wayne State Univ, Sch Med, Dept Emergency Med, Off Student Programs, Detroit, MI 48202 USA. [Wang, Ernest] N Shore Univ Hlth Syst, Div Emergency Med, Ctr Simulat Technol & Acad Res, Evanston, IL USA. [Vozenilek, John A.] Northwestern Univ, Feinberg Sch Med, Dept Emergency Med, Chicago, IL 60611 USA. [Vozenilek, John A.] Northwestern Univ, Feinberg Sch Med, Off Med Educ, Chicago, IL 60611 USA. [Hayden, Emily; Gordon, James A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. [Hayden, Emily; Gordon, James A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gilbert Program Med Simulat, Boston, MA USA. [McLaughlin, Steve] Univ New Mexico, Dept Emergency Med, Albuquerque, NM 87131 USA. [Godwin, Steven A.] Univ Florida, Coll Med Jacksonville, Dept Emergency Med, Jacksonville, FL USA. [Griswold-Theodorson, Sharon; Davenport, Moira] Drexel Univ, Coll Med, Dept Emergency Med, Allegheny Gen Hosp, Philadelphia, PA 19104 USA. RP Fernandez, R (reprint author), Wayne State Univ, Sch Med, Dept Emergency Med, Off Student Programs, Detroit, MI 48202 USA. EM fernanre@comcast.net OI Vozenilek, John/0000-0001-7955-4089 NR 17 TC 12 Z9 12 U1 1 U2 8 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD OCT PY 2010 VL 17 IS 10 BP 1093 EP 1103 DI 10.1111/j.1553-2712.2010.00815.x PG 11 WC Emergency Medicine SC Emergency Medicine GA 663IR UT WOS:000282877400010 PM 21040111 ER PT J AU Senecal, EL Askew, K Gorney, B Beeson, MS Manthey, DE AF Senecal, Emily L. Askew, Kim Gorney, Barbara Beeson, Michael S. Manthey, David E. TI Anatomy of a Clerkship Test SO ACADEMIC EMERGENCY MEDICINE LA English DT Article DE emergency medicine; student; examination; test; evaluation; clerkship ID MULTIPLE-CHOICE QUESTIONS; NATIONAL-BOARD; MEDICAL-EDUCATION; SUBJECT EXAM; STUDENTS; PERFORMANCE; DIRECTORS; CURRICULUM; STEP AB Written examinations are frequently used to assess medical student performance. Within emergency medicine (EM), a National Board of Medical Examiners (NBME) subject examination for EM clerkships does not exist. As a result, clerkship directors frequently generate examinations within their institution. This article reviews the literature behind the use of standardized examinations in evaluating medical student performance, describes methods for generating well-written test questions, reviews the statistical concepts of reliability and validity that are necessary to evaluate an examination, and proposes future directions for testing EM students. ACADEMIC EMERGENCY MEDICINE 2010; 17:S31-S37 (C) 2010 by the Society for Academic Emergency Medicine. C1 [Askew, Kim; Manthey, David E.] Wake Forest Univ, Bowman Gray Sch Med, Dept Emergency Med, Winston Salem, NC USA. [Gorney, Barbara] Wake Forest Univ, Bowman Gray Sch Med, Off Med Educ, Winston Salem, NC USA. [Beeson, Michael S.] Akron Gen Med Ctr, Dept Emergency Med, Akron, OH USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. EM ESenecal@Partners.org RI Manthey, David/C-9936-2013 NR 29 TC 5 Z9 5 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1069-6563 J9 ACAD EMERG MED JI Acad. Emerg. Med. PD OCT PY 2010 VL 17 IS 10 SU 2 BP S31 EP S37 DI 10.1111/j.1553-2712.2010.00880.x PG 7 WC Emergency Medicine SC Emergency Medicine GA 663IU UT WOS:000282877900007 PM 21199081 ER PT J AU Gordon, JA Alexander, EK Lockley, SW Flynn-Evans, E Venkatan, SK Landrigan, CP Czeisler, CA AF Gordon, James A. Alexander, Erik K. Lockley, Steven W. Flynn-Evans, Erin Venkatan, Suresh K. Landrigan, Christopher P. Czeisler, Charles A. CA Harvard Work Hours Hlth Safety Grp TI Does Simulator-Based Clinical Performance Correlate With Actual Hospital Behavior? The Effect of Extended Work Hours on Patient Care Provided by Medical Interns SO ACADEMIC MEDICINE LA English DT Article ID CERTIFICATION EXAMINATION; EMERGENCY MEDICINE; SLEEP; EDUCATION; BOARD AB Purpose The correlation between simulator-based medical performance and real-world behavior remains unclear. This study explored whether the effects of extended work hours on clinical performance, as reported in prior hospital-based studies, could be observed in a simulator-based testing environment. Method Intern volunteers reported to the simulator laboratory in a rested state and again in a sleep-deprived state (after a traditional 24- to 30-hour overnight shift [n = 17]). A subset also presented after a shortened overnight shift (16 scheduled hours [n = 8]). During each laboratory visit, participants managed two critically ill patients. An on-site physician scored each case, as did a blinded rater later watching videotapes of the performances (score = 1 [worst] to 8 [best]; average of both cases = session score). Results Among all participants, the average simulator session score was 6.0 (95% CI: 5.6-6.4) in the rested state and declined to 5.0 (95% CI: 4.6-5.4) after the traditional overnight shift (P <.001). Among those who completed the shortened overnight shift, the average postshift simulator session score was 5.8 (95% CI: 5.0-6.6) compared with 4.3 (95% CI: 3.8-4.9) after a traditional extended shift (P <.001). Conclusions In a clinical simulation test, medical interns performed significantly better after working a shortened overnight shift compared with a traditional extended shift. These findings are consistent with real-time hospital studies using the same shift schedule. Such an independent correlation not only confirms the detrimental impact of extended work hours on medical performance but also supports the validity of simulation as a clinical performance assessment tool. C1 [Gordon, James A.] Massachusetts Gen Hosp, Dept Emergency Med, Div Med Simulat, Gilbert Program Med Simulat, Boston, MA 02114 USA. [Lockley, Steven W.] Harvard Univ, Sch Med, Dept Med, Div Sleep Med, Boston, MA USA. [Landrigan, Christopher P.] Brigham & Womens Hosp, Dept Med, Div Sleep Med, Sleep & Patient Safety Program, Boston, MA 02115 USA. [Landrigan, Christopher P.] Childrens Hosp, Dept Med, Div Gen Pediat, Inpatient Serv, Boston, MA 02115 USA. RP Gordon, JA (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, Div Med Simulat, Gilbert Program Med Simulat, 0 Emerson Pl,Suite 3B, Boston, MA 02114 USA. EM jgordon3@partners.org FU Agency for Healthcare Research and Quality [RO1 HS12032]; National Institute of Occupational Safety and Health within the U.S. Centers for Disease Control [RO1 OH07567]; Department of Medicine, Brigham and Women's Hospital; Division of Sleep Medicine, Harvard Medical School; Brigham and Women's Hospital; National Center for Research Resources; Women's Hospital General Clinical Research Center [M01 RR02635]; Harvard Clinical and Translational Science Center [1 UL1 RR025758]; Brigham and Women's Hospital [NHLBI; T32 HL079010]; National Space Biomedical Research Institute through the National Aeronautics and Space Administration [NCC 9-58] FX This study was supported by grants from both the Agency for Healthcare Research and Quality (RO1 HS12032), which afforded data confidentiality protection by federal statute (Public Health Service Act; 42 U. S. C.), and the National Institute of Occupational Safety and Health within the U.S. Centers for Disease Control (RO1 OH07567), which provided a Certificate of Confidentiality for data protection. Grants from the Department of Medicine, Brigham and Women's Hospital, the Division of Sleep Medicine, Harvard Medical School, and the Brigham and Women's Hospital supported this study as well. Grants from the National Center for Research Resources awarded to the Brigham and Women's Hospital General Clinical Research Center (M01 RR02635) and the Harvard Clinical and Translational Science Center (1 UL1 RR025758) also supported this study.; Ms. Flynn-Evans is the recipient of a predoctoral fellowship in the program of training in Sleep, Circadian and Respiratory Neurobiology at Brigham and Women's Hospital (NHLBI; T32 HL079010). Dr. Lockley and Dr. Czeisler are supported in part by the National Space Biomedical Research Institute through the National Aeronautics and Space Administration (NCC 9-58). NR 14 TC 17 Z9 17 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD OCT PY 2010 VL 85 IS 10 BP 1583 EP 1588 DI 10.1097/ACM.0b013e3181f073f0 PG 6 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 656UN UT WOS:000282365000015 PM 20881679 ER PT J AU Campbell, J Prochazka, AV Yamashita, T Gopal, R AF Campbell, Jessica Prochazka, Allan V. Yamashita, Traci Gopal, Ravi TI Predictors of Persistent Burnout in Internal Medicine Residents: A Prospective Cohort Study SO ACADEMIC MEDICINE LA English DT Article ID PATIENT-CARE; PROGRAM AB Purpose Resident burnout continues to be a major problem despite work hours restrictions. The authors conducted a longitudinal study to determine whether burnout in internal medicine residents is persistent and what factors predispose residents to persistent burnout. Method The authors mailed a survey to internal medicine residents at the University of Colorado Denver Health Science Center each May, from 2003 through 2008. The survey measures included the Maslach Burnout Inventory organized into three subscales: emotional exhaustion (EE), depersonalization (DP), and personal accomplishment. The authors defined burned-out residents as having a high EE or DP score and persistent burnout as being burned out during all three years of residency. Results Of the 179 eligible residents, 86 (48%) responded to the survey during all three years of their residency. Sixty-seven residents (78%) were burned out at least once: 58 residents (67%) were burned out during their internship, 58 (67%) during their second year, and 50 (58%) during their third year (P <.08). Of the 58 burned-out interns, 42 (72%) continued to be burned out through their three years of training. Persistent burnout was more likely to occur in men (OR = 3.31, P <.01) and was associated with screening positive for depression as an intern (OR = 4.4, P <.002). Conclusions Once present, burnout tends to persist through residency. Men and residents who screened positive for depression as interns are at the highest risk for persistent burnout. Interventions to prevent burnout during internship may significantly decrease burnout throughout residency. C1 [Campbell, Jessica; Prochazka, Allan V.; Gopal, Ravi] Univ Colorado Denver, Sch Med, Dept Med, Aurora, CO USA. [Campbell, Jessica] Denver Hlth Med Ctr, Div Hosp Med, Denver, CO USA. [Prochazka, Allan V.; Gopal, Ravi] Denver VA Med Ctr, Denver, CO USA. [Yamashita, Traci] Univ Colorado Denver, Sch Med, Div Gen Internal Med, Aurora, CO USA. RP Campbell, J (reprint author), 660 Bannock St,MC 4000, Denver, CO 80204 USA. EM jessica.campbell@dhha.org FU University of Colorado FX This study was funded in part by the University of Colorado Denver Division of General Internal Medicine Small Grant Program. NR 15 TC 32 Z9 35 U1 0 U2 15 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD OCT PY 2010 VL 85 IS 10 BP 1630 EP 1634 DI 10.1097/ACM.0b013e3181f0c4e7 PG 5 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 656UN UT WOS:000282365000021 PM 20881685 ER PT J AU Fourches, D Pu, DQY Tassa, C Weissleder, R Shaw, SY Mumper, RJ Tropsha, A AF Fourches, Denis Pu, Dongqiuye Tassa, Carlos Weissleder, Ralph Shaw, Stanley Y. Mumper, Russell J. Tropsha, Alexander TI Quantitative Nanostructure-Activity Relationship Modeling SO ACS NANO LA English DT Article DE nanoparticles; QSAR; cheminformatics; nanotoxicity; modeling ID CARBON NANOTUBES; TETRAHYMENA-PYRIFORMIS; VARIABLE SELECTION; NANOTOXICOLOGY; NANOTECHNOLOGY; NANOPARTICLES; TOXICITY; CHEMINFORMATICS; NANOMATERIALS; MOLECULES AB Evaluation of biological effects, both desired and undesired, caused by manufactured nanoparticles (MNPs) is of critical importance for nanotechnology. Experimental studies, especially toxicological, are time-consuming, costly, and often impractical, calling for the development of efficient computational approaches capable of predicting biological effects of MNPs. To this end, we have investigated the potential of cheminformatics methods such as quantitative structure activity relationship (QSAR) modeling to establish statistically significant relationships between measured biological activity profiles of MNPs and their physical, chemical, and geometrical properties, either measured experimentally or computed from the structure of MNPs. To reflect the context of the study, we termed our approach quantitative nanostructure activity relationship (QNAR) modeling. We have employed two representative sets of MNPs studied recently using in vitro cell-based assays: (i) 51 various MNPs with diverse metal cores (Proc. Natl. Acad. Sci. 2008, 105,7387-7392) and (ii) 109 MNPs with similar core but diverse surface modifiers (Nat. Biotechnol. 2005, 23, 1418-1423). We have generated QNAR models using machine learning approaches such as support vector machine (SVM)-based classification and k nearest neighbors (kNN)-based regression; their external prediction power was shown to be as high as 73% for classification modeling and having an R-2 of 0.72 for regression modeling. Our results suggest that ONAR models can be employed for: (i) predicting biological activity profiles of novel nanomaterials, and (ii) prioritizing the design and manufacturing of nanomaterials toward better and safer products. C1 [Fourches, Denis; Pu, Dongqiuye; Tropsha, Alexander] Univ N Carolina, Lab Mol Modeling, UNC Eshelman Sch Pharm, Chapel Hill, NC 27599 USA. [Tassa, Carlos; Weissleder, Ralph; Shaw, Stanley Y.] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Mumper, Russell J.] Univ N Carolina, Ctr Nanotechnol Drug Delivery, UNC Eshelman Sch Pharm, Chapel Hill, NC 27599 USA. RP Tropsha, A (reprint author), Univ N Carolina, Lab Mol Modeling, UNC Eshelman Sch Pharm, Chapel Hill, NC 27599 USA. EM alex_tropsha@unc.edu RI Tropsha, Alexander/G-6245-2014; Mahapatra, Indrani/D-7506-2011 FU Semiconductor Research Corporation (SRC); NIH [R01-GM66940, U01-HL80731]; EPA [RD832720] FX We gratefully acknowledge the support from the Semiconductor Research Corporation (SRC) to A.T. and R.J.M., NIH Grant R01-GM66940 and EPA (Grant RD832720) to AT., and NIH Grant U01-HL80731 to R.W. and S.Y.S. NR 44 TC 126 Z9 129 U1 8 U2 95 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1936-0851 J9 ACS NANO JI ACS Nano PD OCT PY 2010 VL 4 IS 10 BP 5703 EP 5712 DI 10.1021/nn1013484 PG 10 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary SC Chemistry; Science & Technology - Other Topics; Materials Science GA 670UV UT WOS:000283453700031 PM 20857979 ER PT J AU Jupiter, JB Wyss, H AF Jupiter, J. B. Wyss, H. TI Stable Fixation of Osteoporotic Fractures and Nonunions in the Upper Limb - Life Before the "Locking Plate" SO ACTA CHIRURGIAE ORTHOPAEDICAE ET TRAUMATOLOGIAE CECHOSLOVACA LA English DT Review ID UNUNITED FRACTURES; HUMERAL DIAPHYSIS; BLADE PLATE; OSTEOSYNTHESIS; GRAFT AB I have had a wonderful opportunity over the past 30 years to surgically reconstruct many complex fractures and non-unions in the upper limb in the elderly patient with underlying osteoporosis and prior to the development of the "locked plate". This article will present a number of specific techniques using standard LC-DCP and screw in a variety of applications to provide stable internal fixation. These include the use of long plates; creating a "waved plate" initially described by Blatter and Weber; double plating; 3.5 mm intramedullary plate combined with a larger plate on the cortex; custom and machined blade plates as well as enhancement of screw fixation with bone cement and/ or Norian SRS cement. C1 [Jupiter, J. B.; Wyss, H.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02114 USA. RP Jupiter, JB (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Yawkey 2100, Boston, MA 02114 USA. NR 23 TC 9 Z9 9 U1 0 U2 0 PU GALEN SRO PI PRAGUE 5 PA NA BELIDLE 34, PRAGUE 5, 150 00, CZECH REPUBLIC SN 0001-5415 J9 ACTA CHIR ORTHOP TR JI Acta Chir. Orthop. Traumatol. Cechoslov. PD OCT PY 2010 VL 77 IS 5 BP 361 EP 364 PG 4 WC Orthopedics SC Orthopedics GA 673PT UT WOS:000283676100001 PM 21040646 ER PT J AU Brunye, TT Ditman, T Mahoney, CR Walters, EK Taylor, HA AF Brunye, Tad T. Ditman, Tali Mahoney, Caroline R. Walters, Eliza K. Taylor, Holly A. TI You heard it here first: Readers mentally simulate described sounds SO ACTA PSYCHOLOGICA LA English DT Article DE Embodied cognition; Auditory imagery; Language ID LANGUAGE COMPREHENSION; SITUATION MODELS; NARRATIVE COMPREHENSION; SENTENCE COMPREHENSION; PICTURE-RECOGNITION; PERSPECTIVE-TAKING; SEMANTIC MEMORY; MOTOR SYSTEM; INFORMATION; IMAGERY AB The present experiments examined whether readers spontaneously simulate implied auditory elements of sentences. Participants read sentences that implicitly conveyed details that could provoke auditory imagery (e.g., The engine clattered as the truck driver warmed up his rig.), and then performed an unrelated sound categorization task during which they classified sounds as real (occurring in the world) or fake (computer generated). In Experiment 1 these two tasks were performed in sequence; in Experiment 2 they were separated into three experimental blocks to rule out the possibility that readers strategically formed auditory imagery as a result of task demands. In both studies, readers were faster to correctly categorize sounds as 'real' when the sounds had been implied by a preceding sentence. These results suggest that readers mentally simulate the implied auditory characteristics of sentences, even in the absence of tasks that promote mental simulation. Mentally simulating described events is not limited to visual and action-based modalities, further demonstrating the multimodal nature of the perceptual symbols spontaneously activated during reading. Published by Elsevier B.V. C1 [Brunye, Tad T.; Ditman, Tali; Mahoney, Caroline R.; Walters, Eliza K.; Taylor, Holly A.] Tufts Univ, Dept Psychol, Medford, MA 02155 USA. [Brunye, Tad T.; Mahoney, Caroline R.] USA, NSRDEC, Natick, MA 01760 USA. [Ditman, Tali] Harvard Univ, Sch Med, Charlestown, MA USA. [Ditman, Tali] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA. RP Brunye, TT (reprint author), Tufts Univ, Dept Psychol, 490 Boston Ave, Medford, MA 02155 USA. EM tbrunye@alumni.tufts.edu NR 66 TC 10 Z9 12 U1 3 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0001-6918 J9 ACTA PSYCHOL JI Acta Psychol. PD OCT PY 2010 VL 135 IS 2 BP 209 EP 215 DI 10.1016/j.actpsy.2010.06.008 PG 7 WC Psychology, Experimental SC Psychology GA 676CD UT WOS:000283886800020 PM 20621285 ER PT J AU Sharabi, SE Hatef, DA Koshy, JC Hollier, LH Yaremchuk, MJ AF Sharabi, Safa E. Hatef, Daniel A. Koshy, John C. Hollier, Larry H., Jr. Yaremchuk, Michael J. TI Mechanotransduction: The Missing Link in the Facial Aging Puzzle? SO AESTHETIC PLASTIC SURGERY LA English DT Article DE Craniofacial bony remodeling; Craniofacial skeleton; Facial aging; Facial rejuvenation; Mechanotransduction ID SUBORBITAL TROUGH DEFORMITY; AGE-RELATED-CHANGES; 3-DIMENSIONAL STEREOLITHOGRAPHY; LAMBROSS THEORY; SCLERAL SHOW; GROWTH; VERIFICATION; PATHOGENESIS; PARALYSIS; ALGORITHM AB Craniofacial bony remodeling has been recognized as an important contributor to the facial aging process. Multiple studies have demonstrated significant craniofacial skeletal changes with age. However, no review has assembled this information in a concise, cogent fashion. Furthermore, the etiology of these skeletal changes has not been elucidated. This information is important for understanding the mechanisms of facial aging and for further development of facial rejuvenation. A literature review of all articles discussing remodeling of the craniofacial skeleton with age was performed. Studies that used objective measurements of craniofacial skeletal parameters for different age groups were collected and analyzed. The studies demonstrated consistent morphologic changes in the craniofacial skeleton with age. These changes included trends toward increased facial bony width in women; contour changes of the orbit, anterior maxilla, and mandibular body; and decreased dimensions of the glabellar, pyriform, and maxillary angles. The craniofacial skeleton remodels with aging. Many of the observed changes in soft tissue contour and position reflect these skeletal changes. Changes in facial muscle function through the process of mechanotransduction may be responsible for these skeletal changes. C1 [Sharabi, Safa E.; Hatef, Daniel A.; Koshy, John C.; Hollier, Larry H., Jr.] Baylor Coll Med, Div Plast Surg, Houston, TX 77030 USA. [Yaremchuk, Michael J.] Massachusetts Gen Hosp, Div Plast Surg, Boston, MA 02114 USA. RP Hollier, LH (reprint author), Baylor Coll Med, Div Plast Surg, 6701 Fannin St,CC 610 00, Houston, TX 77030 USA. EM larryh@bcm.edu NR 32 TC 9 Z9 11 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-216X J9 AESTHET PLAST SURG JI Aesthet. Plast. Surg. PD OCT PY 2010 VL 34 IS 5 BP 603 EP 611 DI 10.1007/s00266-010-9519-5 PG 9 WC Surgery SC Surgery GA 657PW UT WOS:000282425800010 PM 20440493 ER PT J AU Donnell, D Mimiaga, MJ Mayer, K Chesney, M Koblin, B Coates, T AF Donnell, Deborah Mimiaga, Matthew J. Mayer, Kenneth Chesney, Margaret Koblin, Beryl Coates, Thomas TI Use of Non-Occupational Post-Exposure Prophylaxis does not Lead to an Increase in High Risk Sex Behaviors in Men Who have Sex with Men Participating in the EXPLORE Trial SO AIDS AND BEHAVIOR LA English DT Article DE MSM; HIV; PEP; Behavioral disinhibition ID SIMIAN IMMUNODEFICIENCY VIRUS; BASE-LINE DATA; HIV POSTEXPOSURE; NEWBORN MACAQUES; INFECTION; PREVENTION; EXPOSURE; INTERVENTION; DETERMINANTS; EFFICACY AB Non-occupational post-exposure prophylaxis (nPEP) use is an HIV prevention strategy that has been recommended by the CDC to prevent HIV infection after a high risk sexual exposure since 1997. In a behavioral intervention trial of 4,295 MSM we assessed perceptions and use of nPEP over 4 years in six cities across the United States. Overall, 1.9% of MSM reported use of nPEP prior to enrollment, and 6.3% at least once during the trial. Awareness of nPEP was reported by 47.5%, with higher awareness in two sites with funded nPEP programs. Three seroconversions occurred in the 384 visits where nPEP courses were reported, with no effect of nPEP on risk of HIV acquisition in this cohort (hazard ratio = 0.91, 95% confidence interval [0.29, 2.86]). NPEP users were a riskier group: increased odds of nPEP use were observed in association with multiple partners and unprotected receptive and insertive anal sex with HIV infected partners and partners with unknown HIV status. NPEP use was also associated with use of illicit drugs (injection drugs, crack cocaine, hallucinogens, and amphetamines). Importantly, willingness to use nPEP after high risk sex was associated with lower odds of high risk sex. After an episode of nPEP use, nPEP users remained more likely to report high risk sex than those in this cohort who had not previously used nPEP. However, within the subset of people who had previously reported high risk sex, previous nPEP use was not associated with higher odds of high risk sex, thus allaying fears that availability of nPEP would lead to an increase in high risk sex. C1 [Donnell, Deborah] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Inst, Seattle, WA 98109 USA. [Mimiaga, Matthew J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Mimiaga, Matthew J.; Mayer, Kenneth] Fenway Community Hlth, Fenway Inst, Boston, MA USA. [Chesney, Margaret] Univ Calif San Francisco, Osher Ctr Integrat Med, San Francisco, CA 94143 USA. [Koblin, Beryl] New York Blood Ctr, New York, NY 10021 USA. [Coates, Thomas] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Infect Dis, Los Angeles, CA 90095 USA. RP Donnell, D (reprint author), Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Inst, 1100 Fairview Ave N,POB 10924, Seattle, WA 98109 USA. EM deborah@scharp.org OI Donnell, Deborah/0000-0002-0587-7480 FU NCI NIH HHS [N01 CA035176]; NIAID NIH HHS [U01 AI047995, N01 AI035173, N01 AI045200, N01 AI35173, N01 AI35176, N01 AI45200, U01 AI046749, U01 AI047981, U01 AI048016, U01 AI048040, U01 AI068617, U01 AI46749, U01 AI47981, U01 AI47995, U01 AI48016, U01 AI48040] NR 27 TC 22 Z9 22 U1 3 U2 5 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1090-7165 J9 AIDS BEHAV JI AIDS behav. PD OCT PY 2010 VL 14 IS 5 BP 1182 EP 1189 DI 10.1007/s10461-010-9712-1 PG 8 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 654KU UT WOS:000282168000021 PM 20490908 ER PT J AU Mimiaga, MJ Reisner, SL Bland, S Cranston, K Isenberg, D Driscoll, MA VanDerwarker, R Mayer, KH AF Mimiaga, Matthew J. Reisner, Sari L. Bland, Sean Cranston, Kevin Isenberg, Deborah Driscoll, Maura A. VanDerwarker, Rodney Mayer, Kenneth H. TI "It's a Quick Way to Get What You Want": A Formative Exploration of HIV Risk Among Urban Massachusetts Men Who Have Sex with Men Who Attend Sex Parties SO AIDS PATIENT CARE AND STDS LA English DT Article ID MOBILE VAN SERVICES; BISEXUAL MEN; CAGE QUESTIONNAIRE; UNITED-STATES; SUBSTANCE USE; DRUG-USE; BEHAVIOR; GAY; HEALTH; METHAMPHETAMINE AB Community-based studies with men who have sex with men (MSM) suggest that between 8% and 25% of MSM have met recent male sexual partners at private sex parties. Little is known about HIV sexual risk behaviors of MSM who attend sex parties and whether risk reduction interventions can be delivered in this setting. In 2008, 40 MSM who reported attending and/or hosting sex parties in Massachusetts in the past 12 months completed a qualitative interview and quantitative assessment. Participants reported attending a mean number of 10 sex parties in Massachusetts in the past 12 months. A significant percentage (43%) reported also hosting sex parties. Participants had made sexual partner connections across multiple venues, including public cruising areas, bars/clubs, and the Internet. At the most recent sex party attended, the majority had used alcohol (58%) and/or drugs (50%), and one quarter (25%) put themselves at risk of acquiring or transmitting HIV or other sexually transmitted infections (STIs) by having unprotected anal sex with a mean number of three serodiscordant male sex partners. Although many participants perceived that communicating about sexual health in the sex party context would "ruin the mood,'' the majority (80%) considered some form of HIV prevention at sex parties to be appropriate and necessary, as well as acceptable. Nonintrusive prevention and education activities were especially endorsed (i.e., condoms, lubricants, and coupons for free HIV/STI testing). The majority of participants (75%) expressed some interest in "safer sex'' parties. MSM attending sex parties appear to be a subpopulation at high risk for HIV and STI acquisition and transmission. Risk reduction interventions responsive to the needs of MSM who attend sex parties are warranted. C1 [Mimiaga, Matthew J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat,Behav Med Serv, Boston, MA 02114 USA. [Mimiaga, Matthew J.; Reisner, Sari L.; Bland, Sean; VanDerwarker, Rodney; Mayer, Kenneth H.] Fenway Hlth, Fenway Inst, Boston, MA USA. [Mimiaga, Matthew J.; Reisner, Sari L.] Harvard Univ, Sch Publ Hlth, Boston, MA 02114 USA. [Cranston, Kevin; Isenberg, Deborah; Driscoll, Maura A.] Massachusetts Dept Publ Hlth, Boston, MA USA. [Mayer, Kenneth H.] Brown Univ, Miriam Hosp, Warren Alpert Sch Med, Providence, RI USA. RP Mimiaga, MJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Psychiat,Behav Med Serv, 1 Bowdoin Sq,7th Floor, Boston, MA 02114 USA. EM mmimiaga@partners.org FU Massachusetts Department of Public Health, Office of HIV/AIDS FX This work was supported by the Massachusetts Department of Public Health, Office of HIV/AIDS. NR 55 TC 19 Z9 19 U1 1 U2 5 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1087-2914 J9 AIDS PATIENT CARE ST JI Aids Patient Care STDS PD OCT PY 2010 VL 24 IS 10 BP 659 EP 674 DI 10.1089/apc.2010.0071 PG 16 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 660XW UT WOS:000282682300007 PM 20846008 ER PT J AU Rychert, J Strick, D Bazner, S Robinson, J Rosenberg, E AF Rychert, Jenna Strick, Daryld Bazner, Sue Robinson, James Rosenberg, Eric TI Detection of HIV gp120 in Plasma During Early HIV Infection Is Associated with Increased Proinflammatory and Immunoregulatory Cytokines SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE-ANTIRETROVIRAL-THERAPY; T-CELL; ENVELOPE GLYCOPROTEINS; STRUCTURAL PROTEINS; TYPE-1 INFECTION; LYMPHOID-TISSUE; RESPONSES; P24; NEUTRALIZATION AB Events that occur during acute HIV infection likely contribute to the immune dysfunction common in HIV-infected individuals. During this early stage, there is high-level viral replication, loss in CD4(+) T cell number and function, and an up-regulation of proinflammatory and immunoregulatory cytokines. The mechanisms responsible for this are not completely understood. We hypothesize that the HIV envelope glycoprotein, gp120, contributes to immune dysfunction during early HIV infection. Using a cohort of subjects enrolled during acute and early HIV infection, we determined the amount of gp120, TNF-alpha, IL-6, IL-10, IFN-alpha, and IFN-gamma in plasma at baseline and 6 months. At matched time points, we also measured CD4(+) T cell proliferation, T cell activation, and apoptosis. Plasma from 109 subjects was screened for gp120. Thirty-six subjects (33%) had detectable gp120 (0.5-15.6 ng/ml). Subjects with greater than 1 ng/ml of gp120 at baseline had similar levels at all time points tested, even when viral replication was undetectable due to therapy. Subjects with detectable gp120 had higher levels of plasma IL-6, IL-10, and TNF-alpha. There was no difference in the level of T cell activation, proliferation, or apoptosis in subjects with gp120 compared to those without. We conclude that persistent expression of gp120 occurs in a subset of individuals. Furthermore, the presence of gp120 is associated with higher levels of plasma IL-6, IL-10, and TNF-alpha, which may contribute to immune dysfunction during early HIV infection. C1 [Rosenberg, Eric] Massachusetts Gen Hosp, Div Infect Dis, Dept Med, Boston, MA 02114 USA. [Robinson, James] Tulane Univ, Sch Med, Div Infect Dis, New Orleans, LA 70112 USA. RP Rosenberg, E (reprint author), Massachusetts Gen Hosp, Div Infect Dis, Dept Med, 55 Fruit St, Boston, MA 02114 USA. EM erosenberg1@partners.org FU NIH [R01 AI071915] FX This study was funded by NIH R01 AI071915. NR 30 TC 28 Z9 28 U1 0 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2010 VL 26 IS 10 BP 1139 EP 1145 DI 10.1089/aid.2009.0290 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 665OC UT WOS:000283044200445 PM 20722464 ER PT J AU Bogers, WM Davis, D Mooij, P Koopman, G Verschoor, E Martin, G Martin, L Lai, RPJ Dey, A Sun, Y Siddappa, N Ruprecht, R Montefiori, D Burke, B Srivastava, I Heeney, JL Barnett, S AF Bogers, W. M. Davis, D. Mooij, P. Koopman, G. Verschoor, E. Martin, G. Martin, L. Lai, R. Pei-Jen Dey, A. Sun, Y. Siddappa, N. Ruprecht, R. Montefiori, D. Burke, B. Srivastava, I. Heeney, J. L. Barnett, S. TI HIV-1 envelope-CD4 receptor complexes elicit broad T- and B-cell immune responses as well as cross-reactive neutralizing antibodies in rhesus macaques SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT AIDS Vaccine 2010 CY SEP 28-OCT 01, 2010 CL Atlanta, GA C1 [Bogers, W. M.; Davis, D.; Mooij, P.; Koopman, G.; Verschoor, E.] Biomed Primate Res Ctr, Rijswijk, Netherlands. [Martin, G.; Martin, L.] CEA, Gif Sur Yvette, France. [Lai, R. Pei-Jen; Heeney, J. L.] Univ Cambridge, Cambridge, England. [Dey, A.; Sun, Y.; Burke, B.; Srivastava, I.; Barnett, S.] Novartis, Cambridge, MA USA. [Siddappa, N.; Ruprecht, R.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Montefiori, D.] Duke Univ, Durham, NC USA. RI Dey, Antu/A-1305-2013; MARTIN, loic/E-1627-2011 OI MARTIN, loic/0000-0002-7940-2955 NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2010 VL 26 IS 10 BP A15 EP A16 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 665OC UT WOS:000283044200036 ER PT J AU Bonsignori, M Hwang, K Chen, X Tsao, C Bilska, M Fang, W Marshall, D Whitesides, JF Crump, JA Sam, N Saidi, K Kepler, TB Wu, X Mascola, JR Nabel, GJ Pancera, M Zhu, J Kwong, PD Sodroski, J Lavine, C Yang, X Feng, G Montefiori, DC Liao, H Haynes, BF AF Bonsignori, M. Hwang, K. Chen, X. Tsao, C. Bilska, M. Fang, W. Marshall, D. Whitesides, J. F. Crump, J. A. Sam, N. Saidi, K. Kepler, T. B. Wu, X. Mascola, J. R. Nabel, G. J. Pancera, M. Zhu, J. Kwong, P. D. Sodroski, J. Lavine, C. Yang, X. Feng, G. Montefiori, D. C. Liao, H. Haynes, B. F. TI Immunoregulation of HIV-1 broadly neutralizing antibody responses: deciphering maturation paths for antibody induction SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT AIDS Vaccine 2010 CY SEP 28-OCT 01, 2010 CL Atlanta, GA C1 [Bonsignori, M.; Hwang, K.; Chen, X.; Tsao, C.; Marshall, D.; Whitesides, J. F.; Feng, G.; Liao, H.; Haynes, B. F.] Duke Univ, Med Ctr, Duke Human Vaccine Inst, Durham, NC USA. [Bilska, M.; Fang, W.; Montefiori, D. C.] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. [Crump, J. A.; Sam, N.] Kilimanjaro Christian Med Ctr, Moshi, Tanzania. [Saidi, K.] Harvard Univ, Sch Publ Hlth, Dept Populat & Int Hlth, Boston, MA 02115 USA. [Kepler, T. B.] Duke Univ, Med Ctr, Ctr Computat Immunol, Durham, NC USA. [Wu, X.; Mascola, J. R.; Nabel, G. J.; Pancera, M.; Zhu, J.; Kwong, P. D.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. [Sodroski, J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Lavine, C.; Yang, X.] Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. RI Bonsignori, Mattia/C-6745-2008 NR 0 TC 1 Z9 1 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2010 VL 26 IS 10 BP A153 EP A153 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 665OC UT WOS:000283044200391 ER PT J AU Chen, H Cung, T Beamon, J Seiss, K Huang, J Burke, P Porter, LC Ryan, BJ Weiss, R Brass, AL Rosenberg, ES Walker, BD Yu, XG Lichterfeld, M AF Chen, H. Cung, T. Beamon, J. Seiss, K. Huang, J. Burke, P. Porter, L. C. Ryan, B. J. Weiss, R. Brass, A. L. Rosenberg, E. S. Walker, B. D. Yu, X. G. Lichterfeld, M. TI HIV-1 elite controllers resist HIV-1 infection via p21 (cip-1/waf-1) SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT AIDS Vaccine 2010 CY SEP 28-OCT 01, 2010 CL Atlanta, GA C1 [Chen, H.; Cung, T.; Beamon, J.; Seiss, K.; Huang, J.; Burke, P.; Porter, L. C.; Ryan, B. J.; Brass, A. L.; Walker, B. D.; Yu, X. G.] MIT, Ragon Inst MGH, Charlestown, MA USA. [Chen, H.; Cung, T.; Beamon, J.; Seiss, K.; Huang, J.; Burke, P.; Porter, L. C.; Ryan, B. J.; Brass, A. L.; Walker, B. D.; Yu, X. G.] Harvard, Charlestown, MA USA. [Weiss, R.] Univ Calif Davis, Davis, CA 95616 USA. [Rosenberg, E. S.; Lichterfeld, M.] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2010 VL 26 IS 10 BP A22 EP A23 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 665OC UT WOS:000283044200054 ER PT J AU Finstad, S Zhang, G Jin, C Linde, C Hagan, E de la Rosa, M Zahn, R Wang, X Reimann, K Gaufin, T Apetrei, C Pandrea, I Miller, C McCune, J Picker, L Lifson, J Piatak, M Alter, G Veazey, R Barouch, D Hessell, A Burton, D Nimmerjahn, F Alam, M Haynes, B Gelman, R Brusic, V Letvin, N Schmitz, J AF Finstad, S. Zhang, G. Jin, C. Linde, C. Hagan, E. de la Rosa, M. Zahn, R. Wang, X. Reimann, K. Gaufin, T. Apetrei, C. Pandrea, I. Miller, C. McCune, J. Picker, L. Lifson, J. Piatak, M. Alter, G. Veazey, R. Barouch, D. Hessell, A. Burton, D. Nimmerjahn, F. Alam, M. Haynes, B. Gelman, R. Brusic, V. Letvin, N. Schmitz, J. TI Effect of Fc gamma-receptor polymorphisms in rhesus macaques on SIVmac251 setpoint viremia SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT AIDS Vaccine 2010 CY SEP 28-OCT 01, 2010 CL Atlanta, GA C1 [Zhang, G.; Brusic, V.] Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA. [Gaufin, T.; Veazey, R.] Tulane Univ, Tulane Natl Primate Res Ctr, Covington, LA USA. [Apetrei, C.; Pandrea, I.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. [Miller, C.] Calif Natl Primate Res Ctr, Davis, CA USA. [McCune, J.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Picker, L.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Lifson, J.; Piatak, M.] SAIC Frederick Inc, Natl Canc Inst Frederick, Frederick, MD USA. [Alter, G.] Massachusetts Gen Hosp, Ragon Inst, Charlestown, MA USA. [Barouch, D.] Beth Israel Deaconess Med Ctr, Div Vaccine Res, Boston, MD USA. [Hessell, A.; Burton, D.] Scripps Res Inst, La Jolla, CA 92037 USA. [Nimmerjahn, F.] Univ Erlangen Nurnberg, Erlangen, Germany. [Alam, M.; Haynes, B.] Duke Univ, Med Ctr, Durham, NC USA. [Finstad, S.; Jin, C.; Linde, C.; Hagan, E.; de la Rosa, M.; Zahn, R.; Wang, X.; Reimann, K.; Letvin, N.; Schmitz, J.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RI Nimmerjahn, Falk/J-4986-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2010 VL 26 IS 10 BP A20 EP A20 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 665OC UT WOS:000283044200048 ER PT J AU Henn, M Lennon, N Boutwell, C Malboeuf, C Power, K Casali, M Charlebois, P Berlin, A Macalalad, A Gladden, A Levin, J Ryan, E Erlich, R Young, S Kemper, M Axten, K Streeck, H Zody, M Zedlack, C Brumme, Z Brumme, C Bazner, S Rychert, J Russ, C Rosenberg, E Jessen, H Altfeld, M Birren, B Walker, B Allen, TM AF Henn, M. Lennon, N. Boutwell, C. Malboeuf, C. Power, K. Casali, M. Charlebois, P. Berlin, A. Macalalad, A. Gladden, A. Levin, J. Ryan, E. Erlich, R. Young, S. Kemper, M. Axten, K. Streeck, H. Zody, M. Zedlack, C. Brumme, Z. Brumme, C. Bazner, S. Rychert, J. Russ, C. Rosenberg, E. Jessen, H. Altfeld, M. Birren, B. Walker, B. Allen, T. M. TI Ultra-Deep Sequencing During Acute HIV Infection Reveals Complex Adaptive Changes to Host Selection Pressures SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT AIDS Vaccine 2010 CY SEP 28-OCT 01, 2010 CL Atlanta, GA C1 [Henn, M.; Lennon, N.; Malboeuf, C.; Casali, M.; Charlebois, P.; Berlin, A.; Macalalad, A.; Levin, J.; Ryan, E.; Erlich, R.; Young, S.; Zody, M.; Russ, C.; Birren, B.] Broad Inst, Cambridge, MA USA. [Zedlack, C.; Jessen, H.] HIV Clin Praxis, Berlin, Germany. [Boutwell, C.; Power, K.; Gladden, A.; Kemper, M.; Axten, K.; Streeck, H.; Brumme, Z.; Brumme, C.; Bazner, S.; Rychert, J.; Rosenberg, E.; Altfeld, M.; Walker, B.; Allen, T. M.] Massachusetts Gen Hosp, Charlestown, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2010 VL 26 IS 10 BP A72 EP A72 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 665OC UT WOS:000283044200177 ER PT J AU Lakashe, S Wang, W Siddappa, NB Hu, S Villinger, F Else, JG Ruprecht, RM Rasmussen, R AF Lakashe, S. Wang, W. Siddappa, N. B. Hu, S. Villinger, F. Else, J. G. Ruprecht, R. M. Rasmussen, R. TI Prevention of Systemic Infection by a Multigenic Recombinant Protein Vaccine after Heterologous R5 Clade C SHIV Challenge: Correlates of Protection SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT AIDS Vaccine 2010 CY SEP 28-OCT 01, 2010 CL Atlanta, GA C1 [Hu, S.] Univ Washington, Seattle, WA 98195 USA. [Villinger, F.; Else, J. G.] Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30322 USA. [Lakashe, S.; Wang, W.; Siddappa, N. B.; Ruprecht, R. M.; Rasmussen, R.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2010 VL 26 IS 10 BP A3 EP A4 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 665OC UT WOS:000283044200006 ER PT J AU Liu, J Keele, BF Liu, H Keating, S Norris, PJ Carville, A Mansfield, KG Tomaras, GD Haynes, BF Letvin, NL Hahn, BH Shaw, GM Barouch, DH AF Liu, J. Keele, B. F. Liu, H. Keating, S. Norris, P. J. Carville, A. Mansfield, K. G. Tomaras, G. D. Haynes, B. F. Letvin, N. L. Hahn, B. H. Shaw, G. M. Barouch, D. H. TI Low Dose Mucosal SIV Infection Restricts Early Replication Kinetics and Transmitted Virus Variants in Rhesus Monkeys SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT AIDS Vaccine 2010 CY SEP 28-OCT 01, 2010 CL Atlanta, GA C1 [Liu, J.] Harvard Univ, Sch Med, Boston, MA USA. [Keele, B. F.] NCI, SAIC Frederick, Frederick, MD 21701 USA. [Liu, H.; Hahn, B. H.; Shaw, G. M.] Univ Alabama, Birmingham, AL USA. [Keating, S.; Norris, P. J.] Blood Syst Res Inst, San Francisco, CA USA. [Keating, S.; Norris, P. J.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Carville, A.; Mansfield, K. G.] Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Southborough, MA 01772 USA. [Tomaras, G. D.; Haynes, B. F.] Duke Univ, Med Ctr, Duke Human Vaccine Inst, Durham, NC USA. [Letvin, N. L.] Beth Israel Deaconess Med Ctr, Div Viral Pathogenesis, Boston, MA 02215 USA. [Barouch, D. H.] MGH MIT & Harvard, Ragon Inst, BIDMC, Div Vaccine Res, Boston, MA USA. RI Tomaras, Georgia/J-5041-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2010 VL 26 IS 10 BP A29 EP A29 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 665OC UT WOS:000283044200070 ER PT J AU Titanji, K Velu, V Chennareddi, L Vijay-Kumar, M Gewirtz, AT Freeman, GJ Amara, RR AF Titanji, K. Velu, V. Chennareddi, L. Vijay-Kumar, M. Gewirtz, A. T. Freeman, G. J. Amara, R. R. TI Rapid depletion of Activated memory B cells and Involvement of the PD-1 pathway in Rapidly Progressing SIV infection SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT AIDS Vaccine 2010 CY SEP 28-OCT 01, 2010 CL Atlanta, GA C1 [Vijay-Kumar, M.; Gewirtz, A. T.] Emory Univ, Dept Pathol, Atlanta, GA 30322 USA. [Freeman, G. J.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2010 VL 26 IS 10 BP A47 EP A47 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 665OC UT WOS:000283044200110 ER PT J AU Lugea, A Gong, J Nguyen, J Nieto, J French, SW Pandol, SJ AF Lugea, Aurelia Gong, Jun Nguyen, Janie Nieto, Jose French, Samuel W. Pandol, Stephen J. TI Cholinergic Mediation of Alcohol-Induced Experimental Pancreatitis SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Pancreas; Alcohol Feeding; Cerulein; Cholinergic Pathways; Acetylcholinesterase ID CERULEIN-INDUCED PANCREATITIS; KAPPA-B ACTIVATION; ACINAR-CELLS; ACETYLCHOLINESTERASE ACTIVITY; EXOCRINE SECRETION; ETHANOL; RATS; CHOLECYSTOKININ; KINASE; INJURY AB Objectives: The mechanisms initiating pancreatitis in patients with chronic alcohol abuse are poorly understood. Although alcohol feeding has been previously suggested to alter cholinergic pathways, the effects of these cholinergic alterations in promoting pancreatitis have not been characterized. For this study, we determined the role of the cholinergic system in ethanol-induced sensitizing effects on cerulein pancreatitis. Methods: Rats were pair-fed control and ethanol-containing Lieber-DeCarli diets for 6 weeks followed by parenteral administration of 4 hourly intraperitoneal injections of the cholecystokinin analog, cerulein at 0.5 mu g/kg. This dose of cerulein was selected because it caused pancreatic injury in ethanol-fed but not in control-fed rats. Pancreatitis was preceded by treatment with the muscarinic receptor antagonist atropine or by bilateral subdiaphragmatic vagotomy. Measurement of pancreatic pathology included serum lipase activity, pancreatic trypsin, and caspase-3 activities, and markers of pancreatic necrosis, apoptosis, and autophagy. In addition, we measured the effects of ethanol feeding on pancreatic acetylcholinesterase activity and pancreatic levels of the muscarinic acetylcholine receptors m1 and m3. Finally, we examined the synergistic effects of ethanol and carbachol on inducing acinar cell damage. Results: We found that atropine blocked almost completely pancreatic pathology caused by cerulein administration in ethanol-fed rats, while vagotomy was less effective. Ethanol feeding did not alter expression levels of cholinergic muscarinic receptors in the pancreas but significantly decreased pancreatic acetylcholinesterase activity, suggesting that acetylcholine levels and cholinergic input within the pancreas can be higher in ethanol-fed rats. We further found that ethanol treatment of pancreatic acinar cells augmented pancreatic injury responses caused by the cholinergic agonist, carbachol. Conclusion: These results demonstrate key roles for the cholinergic system in the mechanisms of alcoholic pancreatitis. C1 [Lugea, Aurelia; Gong, Jun; Nguyen, Janie; Nieto, Jose; Pandol, Stephen J.] Vet Affairs Greater Los Angeles Healthcare Syst, USC UCLA Res Ctr Alcohol Liver & Pancreat Dis, Los Angeles, CA 90073 USA. Univ Calif Los Angeles, Los Angeles, CA USA. [French, Samuel W.] Harbor UCLA Med Ctr, Dept Pathol, Torrance, CA 90509 USA. RP Lugea, A (reprint author), Vet Affairs Greater Los Angeles Healthcare Syst, USC UCLA Res Ctr Alcohol Liver & Pancreat Dis, Bldg 258,Room 339,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM alugea@ucla.edu FU National Institute on Alcohol Abuse and Alcoholism (NIAAA) [P50-A11999, 08,116] FX This work was supported by the Department of Veterans Affairs and Research Center for Alcoholic Liver and Pancreatic Diseases (NIAAA P50-A11999) funded by the National Institute on Alcohol Abuse and Alcoholism. We also acknowledge the Animal Core and Morphology Core facilities of the NIAAA-supported Research Center for Alcoholic Liver and Pancreatic Diseases (NIAAA P50-A11999 and NIAAA 08,116 to SW French) for providing assistance with animal alcohol feeding and morphological analyses of pancreatic tissues. NR 66 TC 8 Z9 8 U1 1 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0145-6008 J9 ALCOHOL CLIN EXP RES JI Alcoholism (NY) PD OCT PY 2010 VL 34 IS 10 BP 1768 EP 1781 DI 10.1111/j.1530-0277.2010.01264.x PG 14 WC Substance Abuse SC Substance Abuse GA 656FW UT WOS:000282313600014 PM 20626730 ER PT J AU Teng, E Becker, BW Woo, E Knopman, DS Cummings, JL Lu, PH AF Teng, Edmond Becker, Brian W. Woo, Ellen Knopman, David S. Cummings, Jeffrey L. Lu, Po H. TI Utility of the Functional Activities Questionnaire for Distinguishing Mild Cognitive Impairment From Very Mild Alzheimer Disease SO ALZHEIMER DISEASE & ASSOCIATED DISORDERS LA English DT Article DE mild cognitive impairment; dementia; Alzheimer disease; activities of daily living; standardized assessment ID UNIFORM DATA SET; INSTRUMENTAL ACTIVITIES; OLDER-ADULTS; DEMENTIA; DIAGNOSIS; MCI; INDIVIDUALS; COMMUNITY; DEFICITS; SUBTYPES AB Current criteria for mild cognitive impairment (MCI) require "essentially intact" performance of activities of daily living (ADLs), which has proven difficult to operationalize. We sought to determine how well the Functional Activities Questionnaire (FAQ), a standardized assessment of instrumental ADLs, delineates the clinical distinction between MCI and very mild Alzheimer disease (AD). We identified 1801 individuals in the National Alzheimer's Coordinating Center Uniform Data Set with MCI (n = 1108) or very mild AD (n = 693) assessed with the FAQ and randomized them to the development or test sets. Receiver-operator curve (ROC) analysis of the development set identified optimal cut-points that maximized the sensitivity and specificity of FAQ measures for differentiating AD from MCI and were validated with the test set. ROC analysis of total FAQ scores in the development set produced an area under the curve of 0.903 and an optimal cut-point of 5/6, which yielded 80.3% sensitivity, 87.0% specificity, and 84.7% classification accuracy in the test set. Bill paying, tracking current events, and transportation (P's < 0.005) were the FAQ items of greatest diagnostic utility. These data suggest that the FAQ exhibits adequate sensitivity and specificity when used as a standardized assessment of instrumental ADLs in the diagnosis of AD versus MCI. C1 [Teng, Edmond] Vet Affairs Greater Los Angeles Healthcare Syst, Neurobehav Unit, Los Angeles, CA USA. [Teng, Edmond; Becker, Brian W.] Vet Affairs Greater Los Angeles Healthcare Syst, Geriatr Res Educ & Clin Ctr, Los Angeles, CA USA. [Teng, Edmond; Woo, Ellen; Cummings, Jeffrey L.; Lu, Po H.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. [Cummings, Jeffrey L.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Biobehav Sci, Los Angeles, CA 90095 USA. [Knopman, David S.] Mayo Clin, Dept Neurol, Rochester, MN 55905 USA. RP Teng, E (reprint author), W Los Angeles VA Healthcare Ctr, Neurobehav Unit, Bldg 500 116AF,11301 Wilshire Blvd, Los Angeles, CA 90073 USA. EM eteng@ucla.edu FU National Institute on Aging [P50 AG16570, U01 AG016976]; National Alzheimer's Coordinating Center; Alzheimer's Disease Research Centers of California; Sidell-Kagan Foundation FX This research was supported by the National Institute on Aging (P50 AG16570 U01 AG016976), the National Alzheimer's Coordinating Center, the Alzheimer's Disease Research Centers of California, and the Sidell-Kagan Foundation. NR 33 TC 26 Z9 27 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-0341 J9 ALZ DIS ASSOC DIS JI Alzheimer Dis. Assoc. Dis. PD OCT-DEC PY 2010 VL 24 IS 4 BP 348 EP 353 DI 10.1097/WAD.0b013e3181e2fc84 PG 6 WC Clinical Neurology; Pathology SC Neurosciences & Neurology; Pathology GA 681JN UT WOS:000284308100007 PM 20592580 ER PT J AU Zhu, CW Livote, EE Kahle-Wrobleski, K Scarmeas, N Albert, M Brandt, J Blacker, D Sano, M Stern, Y AF Zhu, Carolyn W. Livote, Elayne E. Kahle-Wrobleski, Kristin Scarmeas, Nikolaos Albert, Marilyn Brandt, Jason Blacker, Deborah Sano, Mary Stern, Yaakov TI Longitudinal Medication Usage in Alzheimer Disease Patients SO ALZHEIMER DISEASE & ASSOCIATED DISORDERS LA English DT Article DE Alzheimer disease; cholinesterase inhibitors; memantine; longitudinal studies ID HEALTH-CARE COSTS; OLDER-ADULTS; DEMENTIA; MULTICENTER; ASSOCIATION; PREDICTORS; DONEPEZIL; TRIALS; PERIOD; SIGNS AB This study examined in detail patterns of cholinesterase inhibitors (ChEIs) and memantine use and explored the relationship between patient characteristics and such use. Patients with probable Alzheimer disease AD (n=201) were recruited from the Predictors Study in 3 academic AD centers and followed from early disease stages for up to 6 years. Random effects logistic regressions were used to examine effects of patient characteristics on ChEIs/memantine use over time. Independent variables included measures of function, cognition, comorbidities, the presence of extrapyramidal signs, psychotic symptoms, age, sex, and patient's living situation at each interval. Control variables included assessment interval, year of study entry, and site. During a 6-year study period, rate of ChEIs use decreased (80.6% to 73.0%) whereas memantine use increased (2.0% to 45.9%). Random effects logistic regression analyses showed that ChEI use was associated with better function, no psychotic symptoms, and younger age. Memantine use was associated with better function, poorer cognition, living at home, later assessment interval, and later year of study entry. Results suggest that high rate of ChEI use and increasing memantine use over time are consistent with current practice guidelines of initiation of ChEIs in mild-to-moderate AD patients and initiation of memantine in moderate-to-severe patients. C1 [Zhu, Carolyn W.; Livote, Elayne E.] James J Peters VA Med Ctr, GRECC, Bronx, NY 10468 USA. [Zhu, Carolyn W.; Livote, Elayne E.] James J Peters VA Med Ctr, HSR&D Ctr Study Hlth Care Syst & Sites Care, Bronx, NY 10468 USA. [Zhu, Carolyn W.; Livote, Elayne E.] Mt Sinai Sch Med, Brookdale Dept Geriatr, New York, NY USA. [Scarmeas, Nikolaos; Stern, Yaakov] Columbia Univ, Med Ctr, Gertrude H Sergievsky Ctr, New York, NY 10027 USA. [Scarmeas, Nikolaos; Stern, Yaakov] Columbia Univ, Med Ctr, Dept Neurol, New York, NY 10027 USA. [Sano, Mary] Mt Sinai Sch Med, Dept Psychol, New York, NY USA. [Kahle-Wrobleski, Kristin] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Scarmeas, Nikolaos; Stern, Yaakov] Taub Inst Res Alzheimers Dis & Aging Brain, Cognit Neurosci Div, New York, NY USA. [Albert, Marilyn; Brandt, Jason] Johns Hopkins Univ, Dept Psychiat & Behav Sci, Baltimore, MD USA. [Blacker, Deborah] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Zhu, CW (reprint author), James J Peters VA Med Ctr, GRECC, 130 W Kingsbridge Rd, Bronx, NY 10468 USA. EM carolyn.zhu@mssm.edu OI Brandt, Jason/0000-0001-7381-6244 FU Federal grants [AG07370, RR00645, U01AG010483]; Eli Lily Company; Department of Veterans Affairs, Veterans Health Administration FX The Predictors Study is supported by Federal grants AG07370, RR00645, and U01AG010483. Funding for this analysis also was partially provided by Eli Lily & Company. Drs Zhu and Sano and Ms Livote also are supported by the Department of Veterans Affairs, Veterans Health Administration. The views expressed in this article are those of the investigators and do not necessarily represent the views of the Department of Veterans Affairs. The investigators all certify that they have no conflict of interest to report in this manuscript. NR 30 TC 4 Z9 4 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0893-0341 J9 ALZ DIS ASSOC DIS JI Alzheimer Dis. Assoc. Dis. PD OCT-DEC PY 2010 VL 24 IS 4 BP 354 EP 359 DI 10.1097/WAD.0b013e3181e6a17a PG 6 WC Clinical Neurology; Pathology SC Neurosciences & Neurology; Pathology GA 681JN UT WOS:000284308100008 PM 20625271 ER PT J AU Ibrahimi, OA Sakamoto, GK Lee, JJ AF Ibrahimi, Omar A. Sakamoto, Greg K. Lee, Jennifer J. TI Acute Onset Vesicular Rash SO AMERICAN FAMILY PHYSICIAN LA English DT Editorial Material C1 [Ibrahimi, Omar A.; Sakamoto, Greg K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. [Lee, Jennifer J.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP Ibrahimi, OA (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA 02115 USA. EM oibrahimi@partners.org NR 1 TC 1 Z9 1 U1 0 U2 0 PU AMER ACAD FAMILY PHYSICIANS PI KANSAS CITY PA 8880 WARD PARKWAY, KANSAS CITY, MO 64114-2797 USA SN 0002-838X J9 AM FAM PHYSICIAN JI Am. Fam. Physician PD OCT 1 PY 2010 VL 82 IS 7 BP 815 EP 816 PG 2 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 663FB UT WOS:000282867300009 PM 20879705 ER PT J AU Hochholzer, W Morrow, DA Giugliano, RP AF Hochholzer, Willibald Morrow, David A. Giugliano, Robert P. TI Novel biomarkers in cardiovascular disease: Update 2010 SO AMERICAN HEART JOURNAL LA English DT Article ID ACUTE CORONARY SYNDROMES; ACUTE MYOCARDIAL-INFARCTION; GROWTH-DIFFERENTIATION FACTOR-15; CARDIAC TROPONIN-I; C-REACTIVE PROTEIN; MEDICINE PRACTICE GUIDELINES; ACUTE CHEST-PAIN; TERMINAL PROVASOPRESSIN COPEPTIN; CHRONIC HEART-FAILURE; RISK STRATIFICATION AB The rapid evaluation of patients presenting with symptoms suggestive of an acute coronary syndrome is of great clinical relevance. Biomarkers have become increasingly important in this setting to supplement electrocardiographic findings and patient history because one or both can be misleading. Today, cardiac troponin is still the only marker used routinely in this setting due to its myocardial tissue specificity and sensitivity, as well as its established usefulness for therapeutic decision making. However, even current generation troponin assays have certain limitations such as insufficient sensitivity for diagnosing unstable angina. Novel high-sensitivity assays for cardiac troponin have the potential to overcome these limitations. Further studies are needed to answer some critical questions regarding the best cutoffs for diagnosis and risk assessment and the optimal work-up for rule-out of acute myocardial infarction. Other nonmyocardial tissue-specific markers might help in this setting. Myeloperoxidase, copeptin, and growth differentiation factor 15 reflect different aspects of the development of atherosclerosis or acute ischemia. Each has demonstrated impact in risk stratification of acute coronary syndromes. Limited data also show that copeptin may, when used together with cardiac troponin, improve the sensitivity for diagnosing acute myocardial infarction, and growth differentiation factor 15 may help in selection of patients that benefit from invasive therapy. Further evaluation is needed before these markers can be adopted routinely in clinical practice. (Am Heart J 2010; 160: 583-94.) C1 [Hochholzer, Willibald; Morrow, David A.; Giugliano, Robert P.] Harvard Univ, Brigham & Womens Hosp, TIMI Study Grp, Cardiovasc Div,Dept Med,Med Sch, Boston, MA 02115 USA. [Hochholzer, Willibald] Herz Zentrum Bad Krozingen, Bad Krozingen, Germany. RP Giugliano, RP (reprint author), Harvard Univ, Brigham & Womens Hosp, TIMI Study Grp, Cardiovasc Div,Dept Med,Med Sch, 350 Longwood Ave,1st Floor, Boston, MA 02115 USA. EM rgiugliano@partners.org FU German Heart Foundation; Accumetrics; Astra-Zeneca; Bayer Healthcare; Beckman Coulter; Biosite; BRAHMS; Bristol-Myers Squibb; CV Therapeutics; Daichii Sankyo Ltd; Eli Lilly and Co; GlaxoSmithKline; Merck and Company; Nanosphere; Novartis Pharmaceuticals; OrthoClinical Diagnostics; Pfizer; Roche Diagnostics; Sanofi-Aventis; Sanofi-Synthelabo; Schering-Plough; Siemens; Singulex FX Dr. Hochholzer was supported by the German Heart Foundation.; Conflict of interest: The TIMI Study Group has received significant research grant support from Accumetrics, Astra-Zeneca, Bayer Healthcare, Beckman Coulter, Biosite, BRAHMS, Bristol-Myers Squibb, CV Therapeutics, Daichii Sankyo Ltd, Eli Lilly and Co, GlaxoSmithKline, Merck and Company, Nanosphere, Novartis Pharmaceuticals, OrthoClinical Diagnostics, Pfizer, Roche Diagnostics, Sanofi-Aventis, Sanofi-Synthelabo, Schering-Plough, Siemens, and Singulex. Dr Hochholzer reports research grant support from Roche Diagnostics. Dr Morrow has received honoraria for educational presentations from CV Therapeutics, and Sanofi-Aventis. He has served as a consultant for Beckman Coulter, Critical Diagnostics, CV Therapeutics, Genentech, Menarini, OrthoClinical Diagnostics, Sanofi-Aventis, Schering Plough, and Siemens. Dr Giugliano reports research grant support from Daiichi-Sankyo, Merck, Schering Plough, and honoraria from consulting and/or CME lectures from Bristol-Myers Squibb, Daiichi-Sankyo, Merck, Pfizer, and Schering Plough. NR 97 TC 88 Z9 92 U1 1 U2 16 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD OCT PY 2010 VL 160 IS 4 BP 583 EP 594 DI 10.1016/j.ahj.2010.06.010 PG 12 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 660WN UT WOS:000282677300007 PM 20934551 ER PT J AU Al-Khatib, SM Calkins, H Eloff, BC Kowey, P Hammill, SC Ellenbogen, KA Marinac-Dabic, D Waldo, AL Brindis, RG Wilbur, DJ Jackman, WM Yaross, MS Russo, AM Prystowsky, E Varosy, PD Gross, T Pinnow, E Turakhia, MP Krucoff, MW AF Al-Khatib, Sana M. Calkins, Hugh Eloff, Benjamin C. Kowey, Peter Hammill, Stephen C. Ellenbogen, Kenneth A. Marinac-Dabic, Danica Waldo, Albert L. Brindis, Ralph G. Wilbur, David J. Jackman, Warren M. Yaross, Marcia S. Russo, Andrea M. Prystowsky, Eric Varosy, Paul D. Gross, Thomas Pinnow, Ellen Turakhia, Mintu P. Krucoff, Mitchell W. TI Developing the Safety of Atrial Fibrillation Ablation Registry Initiative (SAFARI) as a collaborative pan-stakeholder critical path registry model: A Cardiac Safety Research Consortium "Incubator" Think Tank SO AMERICAN HEART JOURNAL LA English DT Article ID ANTIARRHYTHMIC-DRUG THERAPY; PULMONARY-VEIN ABLATION; RADIOFREQUENCY ABLATION; CATHETER ABLATION; RANDOMIZED-TRIAL AB Although several randomized clinical trials have demonstrated the safety and efficacy of catheter ablation of atrial fibrillation (AF) in experienced centers, the outcomes of this procedure in routine clinical practice and in patients with persistent and long-standing persistent AF remain uncertain. Brisk adoption of this therapy by physicians with diverse training and experience highlights potential concerns regarding the safety and effectiveness of this procedure. Some of these concerns could be addressed by a national registry of AF ablation procedures such as the Safety of Atrial Fibrillation Ablation Registry Initiative that was initially proposed at a Cardiac Safety Research Consortium Think Tank meeting in April 2009. In January 2010, the Cardiac Safety Research Consortium, in collaboration with the Duke Clinical Research Institute, the US Food and Drug Administration, the American College of Cardiology, and the Heart Rhythm Society, held a follow-up meeting of experts in the field to review the construct and progress to date. Other participants included the National Heart, Lung, and Blood Institute; the Centers for Medicare and Medicaid Services; the Agency for Healthcare Research and Quality; the AdvaMed AF working group; and additional industry representatives. This article summarizes the discussions that occurred at the meeting of the state of the Safety of Atrial Fibrillation Ablation Registry Initiative, the identification of a clear pathway for its implementation, and the exploration of solutions to potential issues in the execution of this registry. (Am Heart J 2010; 160: 619-626.e1.) C1 [Al-Khatib, Sana M.; Krucoff, Mitchell W.] Duke Univ, Duke Clin Res Inst, Med Ctr, Durham, NC 27715 USA. [Calkins, Hugh] Johns Hopkins Univ, Baltimore, MD USA. [Eloff, Benjamin C.; Marinac-Dabic, Danica; Gross, Thomas; Pinnow, Ellen] US FDA, Silver Spring, MD USA. [Kowey, Peter] Main Line Hlth Heart Ctr, Philadelphia, PA USA. [Hammill, Stephen C.] Mayo Clin, Rochester, MN USA. [Ellenbogen, Kenneth A.] Virginia Commonwealth Univ, Sch Med, Richmond, VA USA. [Waldo, Albert L.] Case Western Reserve Univ, Cleveland, OH 44106 USA. [Brindis, Ralph G.] Amer Coll Cardiol, Washington, DC USA. [Brindis, Ralph G.] Oakland Kaiser Permanente, Oakland, CA USA. [Wilbur, David J.] Loyola Univ, Med Ctr, Chicago, IL 60611 USA. [Jackman, Warren M.] Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. [Yaross, Marcia S.] Biosense Webster, Diamond Bar, CA USA. [Russo, Andrea M.] Cooper Univ Hosp, Robert Wood Johnson Med Sch, Camden, NJ USA. [Prystowsky, Eric] Care Grp, Indianapolis, IN USA. [Varosy, Paul D.] Denver Vet Affairs Med Ctr, Denver, CO USA. [Varosy, Paul D.] Univ Colorado, Denver, CO 80202 USA. [Turakhia, Mintu P.] Palo Alto VA Hlth Care Syst, Palo Alto, CA USA. [Turakhia, Mintu P.] Stanford Univ, Stanford, CA 94305 USA. RP Al-Khatib, SM (reprint author), Duke Univ, Duke Clin Res Inst, Med Ctr, POB 17969, Durham, NC 27715 USA. EM alkha001@mc.duke.edu FU CSRC, DCRI, ACC, HRS; FDA; AdvaMed FX This conference was funded by the CSRC, DCRI, ACC, HRS; registration fees and in-kind support from the FDA and AdvaMed. NR 16 TC 10 Z9 10 U1 1 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD OCT PY 2010 VL 160 IS 4 BP 619 EP U249 DI 10.1016/j.ahj.2010.06.044 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 660WN UT WOS:000282677300010 PM 20934554 ER PT J AU Rodriguez, I Erdman, A Padhi, D Garnett, CE Zhao, H Targum, SL Balakrishnan, S Strnadova, C Viner, N Geiger, MJ Newton-Cheh, C Litwin, J Pugsley, MK Sager, PT Krucoff, MW Finkle, JK AF Rodriguez, Ignacio Erdman, Andrew Padhi, Desmond Garnett, Christine E. Zhao, Hong Targum, Shari L. Balakrishnan, Suchitra Strnadova, Colette Viner, Norman Geiger, Mary Jane Newton-Cheh, Christopher Litwin, Jeffrey Pugsley, Michael K. Sager, Philip T. Krucoff, Mitchell W. Finkle, John K. TI Electrocardiographic assessment for therapeutic proteins-scientific discussion SO AMERICAN HEART JOURNAL LA English DT Article ID HERG POTASSIUM CHANNELS; LONG QT SYNDROME; MONOCLONAL-ANTIBODIES; INTERVAL PROLONGATION; PROARRHYTHMIC RISK; K+ CHANNEL; CARDIOTOXICITY; REPOLARIZATION; TRASTUZUMAB; VASOPRESSIN AB Electrocardiographic monitoring is an integral component of the clinical assessment of cardiac safety of all compounds in development. The International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use E14 guideline recommends a dedicated study to evaluate drug-induced effects on cardiac repolarization ("thorough QT/QTc study"). There has been limited published information on QT interval changes secondary to therapeutic proteins; however, in theory, biologic therapies may affect cardiac electrical activity either directly or indirectly. This article summarizes scientific discussions of members of the Cardiac Safety Research Consortium and includes possible approaches to consider for the clinical evaluation of drug-induced QT prolongation in development programs of therapeutic proteins. (Am Heart J 2010; 160: 627-34.) C1 [Rodriguez, Ignacio] Roche, Nutley, NJ USA. [Erdman, Andrew] Amgen Inc, San Francisco, CA USA. [Padhi, Desmond] Amgen Inc, Thousand Oaks, CA USA. [Garnett, Christine E.; Zhao, Hong; Targum, Shari L.; Balakrishnan, Suchitra] US FDA, Silver Spring, MD USA. [Strnadova, Colette; Viner, Norman] Hlth Canada, Ottawa, ON K1A 0L2, Canada. [Geiger, Mary Jane] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Newton-Cheh, Christopher] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Newton-Cheh, Christopher] Broad Inst Harvard, Cambridge, MA USA. [Newton-Cheh, Christopher] MIT, Cambridge, MA 02139 USA. [Litwin, Jeffrey] ERT, Philadelphia, PA USA. [Pugsley, Michael K.] Johnson & Johnson, Raritan, NJ USA. [Sager, Philip T.] Sager Consulting Partners, San Francisco, CA USA. [Krucoff, Mitchell W.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. [Finkle, John K.] GlaxoSmithKline Inc, Upper Providence, PA USA. RP Rodriguez, I (reprint author), 340 Kingsland St, Nutley, NJ 07110 USA. EM ignacio.rodriguez.ir1@roche.com NR 36 TC 19 Z9 19 U1 0 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD OCT PY 2010 VL 160 IS 4 BP 627 EP 634 DI 10.1016/j.ahj.2010.07.001 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 660WN UT WOS:000282677300011 PM 20934555 ER PT J AU Ruff, CT Giugliano, RP Antman, EM Crugnale, SE Bocanegra, T Mercuri, M Hanyok, J Patel, I Shi, M Salazar, D McCabe, CH Braunwald, E AF Ruff, Christian T. Giugliano, Robert P. Antman, Elliott M. Crugnale, Sharon E. Bocanegra, Tomas Mercuri, Michele Hanyok, James Patel, Indravadan Shi, Minggao Salazar, Dan McCabe, Carolyn H. Braunwald, Eugene TI Evaluation of the novel factor Xa inhibitor edoxaban compared with warfarin in patients with atrial fibrillation: Design and rationale for the Effective aNticoaGulation with factor xA next GEneration in Atrial Fibrillation-Thrombolysis In Myocardial Infarction study 48 (ENGAGE AF-TIMI 48) SO AMERICAN HEART JOURNAL LA English DT Article ID VITAMIN-K ANTAGONISTS; ANTITHROMBOTIC THERAPY; STROKE PREVENTION; THROMBIN; PHARMACOKINETICS; METAANALYSIS; POPULATION; PREVALENCE; MANAGEMENT; REGISTRY AB Background Vitamin K antagonists have been the standard oral antithrombotic used for more than a half century for prevention and treatment of thromboembolism. Their limitations include multiple food and drug interactions and need for frequent monitoring and dose adjustments. Edoxaban is a selective and direct factor Xa inhibitor that may provide effective, safe, and more convenient anticoagulation. Study Design ENGAGE AF-TIMI 48 is a phase 3, randomized, double-blind, double-dummy, multinational, noninferiority design megatrial comparing 2 exposure strategies of edoxaban to warfarin. Approximately 20,500 subjects will be randomized to edoxaban high exposure (60 mg daily, adjusted for drug clearance), edoxaban low exposure (30 mg daily, adjusted for drug clearance), or warfarin titrated to an international normalized ratio of 2.0 to 3.0. The edoxaban strategies provide for dynamic dose reductions in subjects with anticipated increased drug exposure. Blinded treatment is maintained through the use of sham international normalized ratios in patients receiving edoxaban. Eligibility criteria include electrical documentation of atrial fibrillation <= 12 months and a CHADS(2) score >= 2. Randomization is stratified by CHADS(2) score and anticipated drug exposure. The primary objective is to determine whether edoxaban is noninferior to warfarin for the prevention of stroke and systemic embolism. The primary safety end point is modified International Society on Thrombosis and Haemostasis major bleeding. Recruitment began in November 2008. The expected median follow-up is 24 months. Conclusions ENGAGE AF-TIMI 48 is a phase 3 comparison of the novel oral factor Xa inhibitor edoxaban to warfarin for the prevention of thromboembolism in patients with atrial fibrillation. (Am Heart J 2010; 160: 635-641.e2.) C1 [Ruff, Christian T.; Giugliano, Robert P.; Antman, Elliott M.; Crugnale, Sharon E.; McCabe, Carolyn H.; Braunwald, Eugene] Harvard Univ, Brigham & Womens Hosp, TIMI Study Grp, Cardiovasc Div,Dept Med,Med Sch, Boston, MA 02115 USA. [Bocanegra, Tomas; Mercuri, Michele; Hanyok, James; Patel, Indravadan; Shi, Minggao; Salazar, Dan] Daiichi Sankyo Inc, Parsippany, NJ USA. RP Ruff, CT (reprint author), Harvard Univ, Brigham & Womens Hosp, TIMI Study Grp, Cardiovasc Div,Dept Med,Med Sch, 350 Longwood Ave,1st Floor Off, Boston, MA 02115 USA. EM cruff@partners.org NR 30 TC 232 Z9 248 U1 1 U2 15 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD OCT PY 2010 VL 160 IS 4 BP 635 EP U266 DI 10.1016/j.ahj.2010.06.042 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 660WN UT WOS:000282677300012 PM 20934556 ER PT J AU White, H Held, C Stewart, R Watson, D Harrington, R Budaj, A Steg, PG Cannon, CP Krug-Gourley, S Wittes, J Trivedi, T Tarka, E Wallentin, L AF White, Harvey Held, Claes Stewart, Ralph Watson, David Harrington, Robert Budaj, Andrzej Steg, Ph. Gabriel Cannon, Christopher P. Krug-Gourley, Susan Wittes, Janet Trivedi, Trupti Tarka, Elizabeth Wallentin, Lars TI Study design and rationale for the clinical outcomes of the STABILITY Trial (STabilization of Atherosclerotic plaque By Initiation of darapLadIb TherapY) comparing darapladib versus placebo in patients with coronary heart disease SO AMERICAN HEART JOURNAL LA English DT Article ID ACTIVATING-FACTOR ACETYLHYDROLASE; PHOSPHOLIPASE A(2); MYOCARDIAL-INFARCTION; COGNITIVE IMPAIRMENT; OXIDIZED LDL; LIPOPROTEIN; LYSOPHOSPHATIDYLCHOLINE; INHIBITOR; RISK; FAILURE AB Background Elevated plasma levels of lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) are associated with increased risk of cardiovascular (CV) events. Direct inhibition of this proinflammatory enzyme with darapladib may benefit CV patients when given as an adjunct to standard of care, including lipid-lowering and antiplatelet therapies. Methods STABILITY is a randomized, placebo-controlled, double-blind, international, multicenter, event-driven trial. The study has randomized 15,828 patients with chronic coronary heart disease (CHD) receiving standard of care to darapladib enteric-coated (EC) tablets, 160 mg or placebo. Results The primary end point is the composite of major adverse cardiovascular events (MACE): CV death, nonfatal myocardial infarction, and nonfatal stroke. The key secondary end points will include major coronary events, total coronary events, individual components of MACE, and all-cause mortality. Prespecified substudies include 24-hour ambulatory blood pressure monitoring, albuminuria progression, changes in cognitive function, and pharmacokinetic and biomarker analyses. Health economic outcomes and characterization of baseline lifestyle risk factors also will be assessed. The study will continue until 1,500 primary end points have occurred to achieve 90% power to detect a 15.5% reduction in the primary end point. The median treatment duration is anticipated to be 2.75 years. Conclusions STABILITY will assess whether direct inhibition of Lp-PLA(2) with darapladib added to the standard of care confers clinical benefit to patients with CHD. (Am Heart J 2010; 160: 655-661.e2.) C1 [White, Harvey; Stewart, Ralph] Auckland City Hosp, Green Lane Cardiovasc Serv, Auckland 1142, New Zealand. [Held, Claes; Wallentin, Lars] Univ Uppsala Hosp, Uppsala Clin Res Ctr, Uppsala, Sweden. [Watson, David; Krug-Gourley, Susan; Trivedi, Trupti; Tarka, Elizabeth] GlaxoSmithKline Inc, Cardiovasc & Metab MDC, King Of Prussia, PA USA. [Harrington, Robert] Duke Clin Res Inst, Durham, NC USA. [Budaj, Andrzej] Grochowski Hosp, Dept Cardiol, Postgrad Med Sch, Warsaw, Poland. [Steg, Ph. Gabriel] INSERM, U698, Paris, France. [Steg, Ph. Gabriel] Hop Bichat Claude Bernard, Serv Cardiol, F-75877 Paris 18, France. [Steg, Ph. Gabriel] Univ Paris 07, Paris, France. [Cannon, Christopher P.] Brigham & Womens Hosp, Div Cardiovasc, TIMI Study Grp, Boston, MA 02115 USA. [Wittes, Janet] Stat Collaborat Inc NW, Washington, DC USA. RP White, H (reprint author), Auckland City Hosp, Green Lane Cardiovasc Serv, Private Bag 92024,Victoria St W, Auckland 1142, New Zealand. EM harveyw@adhb.govt.nz OI Held, Claes/0000-0001-9402-7404 FU GlaxoSmithKline Pharmaceuticals, King of Prussia, PA, USA; Sanofi-Aventis; Eli Lilly; Medicines Company; National Institutes of Health; Pfizer; Roche; Johnson Johnson; Schering Plough; Merck Sharpe Dohme; AstraZeneca; GlaxoSmithKline; Daiichi-Sankyo Pharma Development; Bristol-Myers Squibb; Regado Biosciences; Portola Pharmaceuticals; Millennium Pharmaceuticals; Boehringer Ingelheim; Novartis; Servier; BMS; Daiichi-Sankyo Lilly; Pierre Fabre; Astellas; Bayer; Daiichi-Sankyo; Medtronic; Otsuka; Accumetrics; Bristol-Myers Squibb/Sanofi; Intekrin Therapeutics; Takeda; Athera; Abbott; Merck FX Sponsored by GlaxoSmithKline Pharmaceuticals, King of Prussia, PA, USA.; H. W. has received research grants from Sanofi-Aventis, Eli Lilly, Medicines Company, National Institutes of Health, Pfizer, Roche, Johnson & Johnson, Schering Plough, Merck Sharpe & Dohme, AstraZeneca, GlaxoSmithKline, Daiichi-Sankyo Pharma Development, and Bristol-Myers Squibb, and he has received a consultancy fee from Regado Biosciences.; C.H. has received institutional research grants from AstraZeneca, Schering Plough, GlaxoSmithKline, and Bristol-Myers Squibb, and he has received a scholarship from Pfizer.; R.S. has no disclosures to declare.; D.W. is an employee of GlaxoSmithKline.; R.H. has received consulting fees from Bristol-Myers Squibb, Sanofi-Aventis, Portola Pharmaceuticals, Schering-Plough, and AstraZeneca; lecture fees from Schering-Plough, Bristol-Myers Squibb, Sanofi-Aventis, and Eli Lilly; and grant support from Millennium Pharmaceuticals, Schering-Plough, The Medicines Company, Portola Pharmaceuticals, AstraZeneca, and Bristol-Myers Squibb.; A.B. has received research grants from Sanofi-Aventis, Boehringer Ingelheim, AstraZeneca, GlaxoSmithKline, and Bristol Meyers Squibb. He has also received consulting fees from Sanofi-Aventis, Eli Lilly, AstraZeneca, Novartis, and lecture fees from Sanofi-Aventis, Boehringer-Ingelheim, AstraZeneca, and GlaxoSmithKline.; G.S. has received a research grant from Servier, speaking grant from AstraZeneca; Boehringer-Ingelheim; BMS; Daiichi-Sankyo Lilly; GlaxoSmithKline; Pierre Fabre; Sanofi-Aventis; Servier; The Medicines Company. He has received a consultancy fee from Astellas, AstraZeneca, Bayer, Boehringer-Ingelheim, BMS, Daiichi-Sankyo, GlaxoSmithKline, Medtronic, Otsuka, Roche, Sanofi-Aventis, Servier, and the Medicines Company. He also has a stockholding with Aterovax.; C.C. has received research grants from Accumetrics, AstraZeneca, Bristol-Myers Squibb/Sanofi Partnership, GlaxoSmithKline, Intekrin Therapeutics, Merck, Novartis, and Takeda. He is also an advisory board member for Bristol-Myers Squibb/Sanofi Partnership (but funds donated to charity) and a clinical Advisor equity in Automedics Medical Systems.; S. K. G. is an employee of GlaxoSmithKline.; J.W. is a consultant for GlaxoSmithKline.; T. T. is an employee of GlaxoSmithKline.; E. T. is an employee of GlaxoSmithKline.; L. W. has received institutional research grants from Eli Lilly, Pfizer, Roche, Schering Plough, Merck Sharpe & Dohme, AstraZeneca, GlaxoSmithKline, Bristol-Myers Squibb, and Boehringer-Ingelheim, and he has received a consultancy fees from Regado Biosciences, Athera, Abbott, Bayer, and Sanofi-Aventis. NR 23 TC 73 Z9 79 U1 0 U2 9 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD OCT PY 2010 VL 160 IS 4 BP 655 EP U289 DI 10.1016/j.ahj.2010.07.006 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 660WN UT WOS:000282677300015 PM 20934559 ER PT J AU Khan, AM Sullivan, L McCabe, E Levy, D Vasan, RS Wang, TJ AF Khan, Abigail May Sullivan, Lisa McCabe, Elizabeth Levy, Daniel Vasan, Ramachandran S. Wang, Thomas J. TI Lack of association between serum magnesium and the risks of hypertension and cardiovascular disease SO AMERICAN HEART JOURNAL LA English DT Article ID CORONARY-HEART-DISEASE; BLOOD-PRESSURE; DIETARY MAGNESIUM; ATHEROSCLEROSIS-RISK; NUTRITIONAL FACTORS; INCIDENT HYPERTENSION; INSULIN-RESISTANCE; NATIONAL SAMPLE; ARTERY-DISEASE; DOUBLE-BLIND AB Background Experimental studies have linked hypomagnesemia with the development of vascular dysfunction, hypertension, and atherosclerosis. Prior clinical studies have yielded conflicting results but were limited by the use of self-reported magnesium intake or short follow-up periods. Methods We examined the relationship between serum magnesium concentration and incident hypertension, cardiovascular disease (CVD), and mortality in 3,531 middle-aged adult participants in the Framingham Heart Study offspring cohort. Analyses were performed using Cox proportional hazards regressions, adjusted for traditional CVD risk factors. Results Follow-up was 8 years for new-onset hypertension (551 events) and 20 years for CVD (554 events). There was no association between baseline serum magnesium and the development of hypertension (multivariable-adjusted hazards ratio per 0.15 mg/dL 1.03, 95% CI 0.92-1.15, P = .61), CVD (0.83, 95% CI 0.49-1.40, P = .49), or all-cause mortality (0.77, 95% CI 0.41-1.45, P = .42). Similar findings were observed in categorical analyses, in which serum magnesium was modeled in categories (<1.5, 1.5-2.2, >2.2 mg/dL) or in quartiles. Conclusions In conclusion, data from this large, community-based cohort do not support the hypothesis that low serum magnesium is a risk factor for developing hypertension or CVD. (Am Heart J 2010; 160: 715-20.) C1 [Khan, Abigail May; McCabe, Elizabeth; Wang, Thomas J.] Harvard Univ, Massachusetts Gen Hosp, Div Cardiol, Dept Med,Med Sch, Boston, MA 02114 USA. [Sullivan, Lisa; Levy, Daniel; Vasan, Ramachandran S.; Wang, Thomas J.] Framingham Heart Dis Epidemiol Study, Framingham, MA USA. [Sullivan, Lisa] Boston Univ, Sch Publ Hlth, Boston, MA USA. [Levy, Daniel; Vasan, Ramachandran S.] Boston Med Ctr, Epidemiol Sect, Boston, MA USA. [Levy, Daniel; Vasan, Ramachandran S.] Boston Med Ctr, Sect Prevent Med, Boston, MA USA. [Levy, Daniel] NHLBI, Ctr Populat Studies, Bethesda, MD 20892 USA. [Vasan, Ramachandran S.] Boston Med Ctr, Cardiol Sect, Boston, MA USA. RP Wang, TJ (reprint author), Harvard Univ, Massachusetts Gen Hosp, Div Cardiol, Dept Med,Med Sch, GRB 800,55 Fruit St, Boston, MA 02114 USA. EM tjwang@partners.org OI Ramachandran, Vasan/0000-0001-7357-5970; Sullivan, Lisa/0000-0003-0726-7149 FU NHLBI NIH HHS [K24 HL004334, N01 HC025195, N01HC25195, R01 HL086875] NR 50 TC 29 Z9 30 U1 0 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD OCT PY 2010 VL 160 IS 4 BP 715 EP 720 DI 10.1016/j.ahj.2010.06.036 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 660WN UT WOS:000282677300022 PM 20934566 ER PT J AU Sowden, G Huffman, JC AF Sowden, Gillian Huffman, Jeff C. TI Is screening cardiac inpatients for depression really feasible? SO AMERICAN HEART JOURNAL LA English DT Letter ID CARE C1 [Sowden, Gillian; Huffman, Jeff C.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. RP Sowden, G (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. EM jhuffman@partners.org NR 2 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 0002-8703 J9 AM HEART J JI Am. Heart J. PD OCT PY 2010 VL 160 IS 4 BP E31 EP E31 DI 10.1016/j.ahj.2010.07.031 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 660WN UT WOS:000282677300002 ER PT J AU Samlowski, WE Moon, J Tuthill, RJ Heinrich, MC Balzer-Haas, NS Merl, SA DeConti, RC Thompson, JA Witter, MT Flaherty, LE Sondak, VK AF Samlowski, Wolfram E. Moon, James Tuthill, Ralph J. Heinrich, Michael C. Balzer-Haas, Naomi S. Merl, Stuart A. DeConti, Ronald C. Thompson, John A. Witter, Merle T. Flaherty, Lawrence E. Sondak, Vernon K. TI A Phase II Trial of Imatinib Mesylate in Merkel Cell Carcinoma (Neuroendocrine Carcinoma of the Skin) A Southwest Oncology Group Study (S0331) SO AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS LA English DT Article DE Merkel cell carcinoma; neuroendocrine carcinoma of the skin; imatinib mesylate; c-KIT ID CHRONIC MYELOID-LEUKEMIA; ABL TYROSINE KINASE; CLINICAL BEHAVIOR; CD117 EXPRESSION; KIT; CHEMOTHERAPY; TUMORS; 5-FLUOROURACIL; POLYOMAVIRUS; INHIBITOR AB Background: Imatinib mesylate (Gleevec) was evaluated as a treatment for Merkel cell carcinoma (MCC, neuroendocrine carcinoma of the skin) based on the identification of strong c-KIT staining of these neoplasms. Methods: Eligibility included patients with measurable metastatic or unresectable MCC, c-KIT (CD117) expression and a Zubrod performance status of 0 to 2. Imatinib 400 mg daily was administered orally in 28-day cycles to 23 patients. Results: Overall, imatinib was well tolerated with grade 1 or 2 nausea, diarrhea, and hematologic toxicity as the most frequent side effects. A partial response was seen in 1 patient (4%; 95% CI: 0%-22%). Median progression-free survival was 1 month (95% CI: 1-2 months). Median overall survival was 5 months (95% CI: 2-8 months). One patient achieved a partial response and another had prolonged disease stabilization while receiving treatment. Conclusions: The majority of patients progressed rapidly within 1 to 2 cycles of treatment. The observed progression-free survival and overall survival were not adequate to conclude that this agent was active in advanced MCC, and thus the planned second stage of patient accrual was not opened. C1 [Samlowski, Wolfram E.; Witter, Merle T.; Sondak, Vernon K.] Nevada Canc Inst, Las Vegas, NV USA. [Moon, James] SW Oncol Grp, Ctr Stat, Seattle, WA USA. [Tuthill, Ralph J.] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Heinrich, Michael C.] Portland VA Med Ctr, Portland, OR USA. [Heinrich, Michael C.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Balzer-Haas, Naomi S.] Univ Penn ECOG, Abramson Canc Ctr, Philadelphia, PA USA. [Merl, Stuart A.] Dayton Clin Oncol Program, Dayton, OH USA. [DeConti, Ronald C.] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. [Thompson, John A.] Puget Sound Oncol Consortium, Seattle, WA USA. [Flaherty, Lawrence E.] Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. RP Samlowski, WE (reprint author), SW Oncol Grp, Chairs Off S0331, 24 Frank Lloyd Wright Dr,POB 483, Ann Arbor, MI 48106 USA. EM arlauska@med.umich.edu OI Samlowski, Wolfram/0000-0002-0713-914X FU National Cancer Institute, DHHS [CA32102, CA38926, CA35090, CA073590, CA20319), CA45377, A35178, CA35176, CA46113, CA46441, CA42777, CA86780, CA58861, CA46282, CA35119, CA15488, CA21115] FX Supported, in part, by the following PHS Cooperative Agreement grant numbers awarded by the National Cancer Institute, DHHS: CA32102, CA38926, CA35090, CA073590, CA20319), CA45377, CA35178, CA35176, CA46113, CA46441, CA42777, CA86780, CA58861, CA46282, CA35119, CA15488, CA21115. NR 35 TC 30 Z9 30 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3732 J9 AM J CLIN ONCOL-CANC JI Am. J. Clin. Oncol.-Cancer Clin. Trials PD OCT PY 2010 VL 33 IS 5 BP 495 EP 499 DI 10.1097/COC.0b013e3181b9cf04 PG 5 WC Oncology SC Oncology GA 659WT UT WOS:000282598700013 PM 20019577 ER PT J AU Shear, ML Adler, JN Shewakramani, S Ilgen, J Soremekun, OA Nelson, S Thomas, SH AF Shear, Melissa L. Adler, Jonathan N. Shewakramani, Sanjay Ilgen, Jon Soremekun, Olanrewaju A. Nelson, Sara Thomas, Stephen H. TI Transbuccal fentanyl for rapid relief of orthopedic pain in the ED SO AMERICAN JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID DOSE PROPORTIONALITY; HEALTHY-VOLUNTEERS; LACERATION REPAIR; BUCCAL TABLETS; DOUBLE-BLIND; ANALGESIA; EMERGENCY; TRAUMA; FRACTURES; CHILDREN AB Objectives: This study's objectives were to assess administration of a rapidly dissolving transbuccal fentanyl tablet to patients in emergency department (ED) with orthopedic extremity pain. The main end point was time required to achieve a 2-point drop on a 0 to 10 pain scale. Methods: In this double-blind trial, subjects received either transbuccal fentanyl, 100 mu g, and a swallowed placebo, or a swallowed oxycodone/acetaminophen, 5/325-mg pill, and a nonanalgesic transbuccal comparator. Pain assessment occurred every 5 minutes for an hour, and vital signs were monitored for 2 hours. Results: Transbuccal fentanyl was associated with faster pain relief onset (median, 10 vs 35 minutes; P < .0001). Secondary end points (pain relief magnitude, rescue medication rate, subject preference for medication on future visit) favored transbuccal fentanyl. No vital sign abnormalities or significant side effects occurred in the ED or on 100% next-day follow-up. Conclusions: Transbuccal fentanyl shows promise for continued investigation as a means to safely provide rapid and effective pain relief for ED patients. (C) 2010 Elsevier Inc. All rights reserved. C1 [Thomas, Stephen H.] Univ Oklahoma, Sch Community Med, OU Schusterman Ctr, Dept Emergency Med, Tulsa, OK 74135 USA. [Shear, Melissa L.; Adler, Jonathan N.; Shewakramani, Sanjay; Ilgen, Jon; Soremekun, Olanrewaju A.; Nelson, Sara] Massachusetts Gen Hosp, Emergency Serv, Boston, MA 02114 USA. [Shear, Melissa L.; Adler, Jonathan N.; Shewakramani, Sanjay; Ilgen, Jon; Soremekun, Olanrewaju A.; Nelson, Sara] Harvard Univ, Sch Med, Boston, MA 02114 USA. RP Thomas, SH (reprint author), Univ Oklahoma, Sch Community Med, OU Schusterman Ctr, Dept Emergency Med, Tulsa, OK 74135 USA. EM stephen-thomas@ouhsc.edu FU Harvard Medical School Division of Emergency Medicine FX Unrestricted grant from the Harvard Medical School Division of Emergency Medicine. NR 43 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 EI 1532-8171 J9 AM J EMERG MED JI Am. J. Emerg. Med. PD OCT PY 2010 VL 28 IS 8 BP 847 EP 852 DI 10.1016/j.ajem.2009.04.011 PG 6 WC Emergency Medicine SC Emergency Medicine GA 660TV UT WOS:000282669300001 PM 20887903 ER PT J AU Kessler, C Chen, J Dill, C Tyndall, G Olszyk, MD AF Kessler, Chad Chen, Jennifer Dill, Curt Tyndall, Gary Olszyk, Mark D. TI State of affairs of emergency medicine in the Veterans Health Administration SO AMERICAN JOURNAL OF EMERGENCY MEDICINE LA English DT Article ID QUALITY-OF-CARE; CENTERS; SYSTEM AB Background: The Veterans Health Administration (VHA) has reformed its emergency medical services. Objectives: This study updates an overview of emergency medicine within VHA. Methods: This is a cross-sectional survey of VHA medical facilities offering emergency medical care. Results: Sixty-eight percent (95/140) of facilities had emergency departments (EDs) only, 12% (16/140) had both ED and urgent care centers (UCCs), and 16% (23/140) had only UCCs. The mean (SD) ED/UCC census was 13 371 (7664). A mean (SD) of 53% (27%) of facility admissions were admitted through ED/UCCs. The median of all ED/UCC admissions admitted to intensive care unit level care was 11% (interquartile range, 7-16). Of physicians with any board certification, 16% (209/1331) of physicians had emergency medicine board certification. Conclusions: Emergency medical care is now available at most VHA facilities. The specialty of emergency medicine has an important but minority presence within clinical emergency medical care at VHA. Published by Elsevier Inc. C1 [Chen, Jennifer] W Los Angeles VA Med Ctr, David Geffen UCLA Sch Med, Dept Med, Los Angeles, CA 90073 USA. [Kessler, Chad] Univ Illinois, Jesse Brown VA Hosp, Dept Internal Med, Chicago, IL 60612 USA. [Kessler, Chad] Univ Illinois, Jesse Brown VA Hosp, Dept Emergency Med, Chicago, IL 60612 USA. [Dill, Curt] NYU, Sch Med, VA New York Harbor Healthcare Ctr, Dept Emergency Serv, Brooklyn, NY 11209 USA. [Tyndall, Gary] Syracuse VAMC, Emergency Serv, Syracuse, NY 13210 USA. [Olszyk, Mark D.] VA Maryland Healthcare Syst, Emergency Serv, Baltimore, MD 21201 USA. RP Chen, J (reprint author), W Los Angeles VA Med Ctr, David Geffen UCLA Sch Med, Dept Med, Los Angeles, CA 90073 USA. EM jen.chencn@gmail.com OI Chen, Jennifer/0000-0002-4801-5397; Tyndall, Gary/0000-0001-9984-4809 NR 10 TC 8 Z9 8 U1 1 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 0735-6757 J9 AM J EMERG MED JI Am. J. Emerg. Med. PD OCT PY 2010 VL 28 IS 8 BP 947 EP 951 DI 10.1016/j.ajem.2009.08.008 PG 5 WC Emergency Medicine SC Emergency Medicine GA 660TV UT WOS:000282669300019 PM 20887913 ER PT J AU Shah, S Dalal, A Smith, RM Joseph, G Rogers, S Dyer, GSM AF Shah, Sachita Dalal, Akshay Smith, R. Malcolm Joseph, Giliane Rogers, Selwyn Dyer, George S. M. TI Impact of portable ultrasound in trauma care after the Haitian earthquake of 2010 SO AMERICAN JOURNAL OF EMERGENCY MEDICINE LA English DT Letter ID MASS CASUALTIES C1 [Shah, Sachita] Rhode Isl Hosp, Dept Emergency Med, Providence, RI 02903 USA. [Dalal, Akshay] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Management, Boston, MA 02114 USA. [Smith, R. Malcolm] Massachusetts Gen Hosp, Dept Orthoped, Boston, MA 02114 USA. [Joseph, Giliane] Montefiore Med Ctr, Albert Einstein Coll Med, Dept Med, Div Infect Dis, Bronx, NY 10467 USA. [Rogers, Selwyn] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Dyer, George S. M.] Brigham & Womens Hosp, Dept Orthoped, Boston, MA 02115 USA. RP Shah, S (reprint author), Rhode Isl Hosp, Dept Emergency Med, Providence, RI 02903 USA. EM sachita.shah@gmail.com NR 6 TC 6 Z9 6 U1 0 U2 4 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0735-6757 J9 AM J EMERG MED JI Am. J. Emerg. Med. PD OCT PY 2010 VL 28 IS 8 BP 970 EP 971 DI 10.1016/j.ajem.2010.06.017 PG 2 WC Emergency Medicine SC Emergency Medicine GA 660TV UT WOS:000282669300024 PM 20708876 ER PT J AU Whitcomb, DC Muddana, V Langmead, CJ Houghton, FD Guenther, A Eagon, PK Mayerle, J Aghdassi, AA Weiss, FU Evans, A Lamb, J Clermont, G Lerch, MM Papachristou, GI AF Whitcomb, David C. Muddana, Venkata Langmead, Christopher J. Houghton, Frank D., Jr. Guenther, Annett Eagon, Patricia K. Mayerle, Julia Aghdassi, Ali A. Weiss, F. Ulrich Evans, Anna Lamb, Janette Clermont, Gilles Lerch, Markus M. Papachristou, Georgios I. TI Angiopoietin-2, a Regulator of Vascular Permeability in Inflammation, Is Associated With Persistent Organ Failure in Patients With Acute Pancreatitis From the United States and Germany SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID CIRCULATING ANGIOPOIETIN-2; SEPSIS; MULTICENTER; POPULATION; MORTALITY; SEVERITY; MEDIATOR; INJURY; SCORE; LEAK AB OBJECTIVES: Patients with severe acute pancreatitis (AP) typically develop vascular leak syndrome, resulting in hemoconcentration, hypotension, pulmonary edema, and renal insufficiency. Angiopoietin-1 (Ang-1) and 2 (Ang-2) are autocrine peptides that reduce or increase endothelial permeability, respectively. The aim of this study was to determine whether Ang-1 and/or Ang-2 levels are predictive biomarkers of persistent organ failure (>48h) and prolonged hospital course. METHODS: Banked serum from 28 patients enrolled in the Severity of Acute Pancreatitis Study at the University of Pittsburgh Medical Center (UPMC) and 58 controls was analyzed for Ang-1 and Ang-2 levels. Separately, serum from 123 patients and 103 controls at Greifswald University (GU), Germany was analyzed for Ang-2 levels. Angiopoietin levels were measured by enzyme-linked immunosorbent assay. RESULTS: In all, 6 out of 28 UPMC patients (21%) and 14 out of 123 GU patients (13%) developed persistent organ failure and were classified as severe AP. Ang-2 was significantly higher on admission in patients who developed persistent organ failure compared with those who did not in UPMC (3,698 pg/ml vs. 1,001 pg/ml; P=0.001) and GU (4,945 pg/ml vs. 2,631 pg/ml; P=0.0004) cohorts. After data scaling, admission Ang-2 levels showed a receiver-operator curve of 0.81, sensitivity 90%, and specificity 67% in predicting persistent organ failure. In addition, Ang-2 levels remained significantly higher in severe AP compared with mild AP patients until day 7 (days 2-4: P<0.005; day 7: P<0.02). Ang-1 levels were not significantly different between mild and severe AP patients on admission. CONCLUSIONS: Elevated serum Ang-2 levels on admission are associated with and may be a useful biomarker of predicting persistent organ failure and ongoing endothelial cell activation in AP. C1 [Whitcomb, David C.; Muddana, Venkata; Houghton, Frank D., Jr.; Eagon, Patricia K.; Evans, Anna; Lamb, Janette; Papachristou, Georgios I.] Univ Pittsburgh, Dept Med, Div Gastroenterol Hepatol & Nutr, Med Ctr, Pittsburgh, PA 15213 USA. [Whitcomb, David C.] Univ Pittsburgh, Sch Med, Dept Cell Biol, Pittsburgh, PA 15213 USA. [Whitcomb, David C.] Univ Pittsburgh, Sch Med, Dept Physiol, Pittsburgh, PA 15213 USA. [Whitcomb, David C.] Univ Pittsburgh, Sch Med, Dept Human Genet, Pittsburgh, PA 15213 USA. [Langmead, Christopher J.] Carnegie Mellon Univ, Dept Comp Sci, Pittsburgh, PA 15213 USA. [Guenther, Annett; Mayerle, Julia; Aghdassi, Ali A.; Weiss, F. Ulrich; Lerch, Markus M.] Ernst Moritz Arndt Univ Greifswald, Dept Med A, Greifswald, Germany. [Clermont, Gilles] Univ Pittsburgh, Dept Crit Care Med, Pittsburgh, PA 15213 USA. [Clermont, Gilles; Papachristou, Georgios I.] Vet Affairs Pittsburgh Hlth Syst, Pittsburgh, PA USA. RP Whitcomb, DC (reprint author), Univ Pittsburgh, Dept Med, Div Gastroenterol Hepatol & Nutr, Med Ctr, Room 401-4,3708 5th Ave, Pittsburgh, PA 15213 USA. EM whitcomb@pitt.edu RI Lerch, Markus M./E-2206-2016; Weiss, Frank/A-6386-2009; OI Lerch, Markus M./0000-0002-9643-8263; Weiss, Frank Ulrich/0000-0003-3369-6369 FU National Pancreas Foundation; VA Stars Competitive Pilot Project Fund (CPPF); DFG [LE 625/8-1, 9-1, GRK 840 E3, E4]; Alfried-Krupp Foundation; [BMBF-NBL3 01 ZZ 0403] FX This study was funded by the National Pancreas Foundation (D. C. W.), the VA Stars Competitive Pilot Project Fund (CPPF), DFG LE 625/8-1 and 9-1, the Alfried-Krupp Foundation, DFG GRK 840 E3 and E4, and BMBF-NBL3 01 ZZ 0403. NR 20 TC 28 Z9 29 U1 2 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2010 VL 105 IS 10 BP 2287 EP 2292 DI 10.1038/ajg.2010.183 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 659US UT WOS:000282593000023 PM 20461065 ER PT J AU Ben, M Rotkowitz, L Gornstein, B Ratner, L Martin, H AF Ben, Matthew Rotkowitz, Louis Gornstein, Bradley Ratner, Lee Martin, Hertl TI A 27-Year-Old Woman with Right Upper Quadrant Pain and Elevated Liver Enzymes SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 75th Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 15-20, 2010 CL San Antonio, TX SP Amer Coll Gastroenterol C1 [Rotkowitz, Louis] Albany Med Ctr, Albany, NY USA. [Ben, Matthew; Gornstein, Bradley; Ratner, Lee] St Peters Hosp, Albany, NY USA. [Martin, Hertl] Massachusetts Gen Hosp, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2010 VL 105 SU 1 MA 735 BP S265 EP S266 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 663VG UT WOS:000282917700729 ER PT J AU Chavalitdhamrong, D Giri, B Luthra, M AF Chavalitdhamrong, Disaya Giri, Badri Luthra, Munish TI Acute Autoimmune Hepatitis Mimicking an Acute Abdomen SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 75th Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 15-20, 2010 CL San Antonio, TX SP Amer Coll Gastroenterol C1 [Chavalitdhamrong, Disaya; Giri, Badri; Luthra, Munish] Mt Sinai Sch Med Bronx Program, James J Peters Vet Affairs Med Ctr, Bronx, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2010 VL 105 SU 1 MA 731 BP S264 EP S264 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 663VG UT WOS:000282917700725 ER PT J AU Cheifetz, A Melmed, G Spiegel, B Talley, J Devlin, S Harrell, L Irving, P Jones, J Kaplan, G Kozuch, P Sparrow, M Velayos, F Baidoo, L Bressler, B Siegel, C AF Cheifetz, Adam Melmed, Gil Spiegel, Brennan Talley, Jennifer Devlin, Shane Harrell, Laura Irving, Peter Jones, Jennifer Kaplan, Gil Kozuch, Patricia Sparrow, Miles Velayos, Fernando Baidoo, Leonard Bressler, Brian Siegel, Corey TI Setting Priorities for Comparative Effectiveness Research in Inflammatory Bowel Disease: Results of an International Provider Survey, Expert RAND Panel, and Patient Focus Groups SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 75th Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 15-20, 2010 CL San Antonio, TX SP Amer Coll Gastroenterol C1 [Cheifetz, Adam] Beth Israel Deaconess Med Ctr, Med GI, Boston, MA 02215 USA. [Melmed, Gil] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Spiegel, Brennan] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Talley, Jennifer] CURE Digest Dis Res Ctr, Los Angeles, CA USA. [Devlin, Shane; Kaplan, Gil] Univ Calgary, Calgary, AB, Canada. [Harrell, Laura] Univ Chicago, Chicago, IL 60637 USA. [Irving, Peter] Guys & St Thomas Hosp, London SE1 9RT, England. [Jones, Jennifer] Univ Saskatchewan, Saskatoon, SK, Canada. [Kozuch, Patricia] Thomas Jefferson Univ, Philadelphia, PA 19107 USA. [Sparrow, Miles] Alfred Hosp, Melbourne, Vic, Australia. [Velayos, Fernando] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Baidoo, Leonard] Univ Pittsburgh, Pittsburgh, PA USA. [Bressler, Brian] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Siegel, Corey] Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2010 VL 105 SU 1 MA 1147 BP S415 EP S416 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 663VG UT WOS:000282917701337 ER PT J AU Goede, L Knudsen, A van Ballegooijen, M Kuntz, K Lansdorp-Vogelaar, I Tangka, F Howard, D Zauber, A Seeff, L AF Goede, Luuk Knudsen, Amy van Ballegooijen, Marjolein Kuntz, Karen Lansdorp-Vogelaar, Iris Tangka, Florence Howard, David Zauber, Ann Seeff, Laura TI Cost-Savings to Medicare from Increased Colorectal Cancer Screening in the Pre-Medicare Population SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 75th Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 15-20, 2010 CL San Antonio, TX SP Amer Coll Gastroenterol C1 [Goede, Luuk; van Ballegooijen, Marjolein; Lansdorp-Vogelaar, Iris] Erasmus MC, Rotterdam, Netherlands. [Knudsen, Amy] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Kuntz, Karen] Univ Minnesota, Minneapolis, MN USA. [Tangka, Florence; Seeff, Laura] Ctr Dis Control & Prevent, Atlanta, GA USA. [Howard, David] Emory Univ, Atlanta, GA 30322 USA. [Zauber, Ann] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2010 VL 105 SU 1 MA 1095 BP S397 EP S397 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 663VG UT WOS:000282917701285 ER PT J AU Harris, A Shah, S Leleiko, N Lidofsky, S Bright, R Grabert, S Law, M Moniz, H Bancroft, B Suorsa, K Patel, M Vancura, J Kalasapudi, B Cole, E Sands, B AF Harris, Adam Shah, Samir Leleiko, Neal Lidofsky, Sheldon Bright, Renee Grabert, Stacey Law, Meaghan Moniz, Heather Bancroft, Barbara Suorsa, Kristina Patel, Mitul Vancura, Jennifer Kalasapudi, Bharati Cole, Elisabeth Sands, Bruce TI Medical Therapy of IBD in the First Year After Diagnosis: Preliminary Results from the Ocean State Crohn's and Colitis Area Registry (OSCCAR) SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 75th Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 15-20, 2010 CL San Antonio, TX SP Amer Coll Gastroenterol C1 [Harris, Adam; Shah, Samir; Leleiko, Neal; Lidofsky, Sheldon; Bright, Renee; Law, Meaghan; Moniz, Heather; Bancroft, Barbara; Suorsa, Kristina; Patel, Mitul; Vancura, Jennifer; Kalasapudi, Bharati] Lifespan, Providence, RI USA. [Harris, Adam; Shah, Samir; Leleiko, Neal; Lidofsky, Sheldon; Bright, Renee; Law, Meaghan; Moniz, Heather; Bancroft, Barbara; Suorsa, Kristina; Patel, Mitul; Vancura, Jennifer; Kalasapudi, Bharati] Brown Univ, Providence, RI 02912 USA. [Grabert, Stacey; Cole, Elisabeth] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sands, Bruce] Mt Sinai Sch Med, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2010 VL 105 SU 1 MA 1175 BP S427 EP S427 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 663VG UT WOS:000282917701365 ER PT J AU Kuo, B Maneerattanaporn, M Lee, A Baker, J Wiener, S Chey, W Wilding, G Hasler, W AF Kuo, Braden Maneerattanaporn, Monthira Lee, Allen Baker, Jason Wiener, Stephen Chey, William Wilding, Gregory Hasler, William TI Generalized Transit Delay on Wireless Motility Capsule in Patients with Clinical Suspicion of Gastroparesis, Intestinal Dysmotility, or Slow Transit Constipation SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 75th Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 15-20, 2010 CL San Antonio, TX SP Amer Coll Gastroenterol C1 [Kuo, Braden; Lee, Allen; Wiener, Stephen] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Maneerattanaporn, Monthira; Baker, Jason; Chey, William; Hasler, William] Univ Michigan Hlth Syst, Ann Arbor, MI USA. [Wilding, Gregory] SUNY Buffalo, Buffalo, NY 14260 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2010 VL 105 SU 1 MA 1356 BP S501 EP S502 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 663VG UT WOS:000282917701545 ER PT J AU Long, M Crandall, W Leibowitz, I Duffy, L del Rosario, F Kim, S Integlia, M Berman, J Grunow, J Colletti, R Schoen, B Patel, A Baron, H Israel, E Russell, G Ali, S Herfarth, H Martin, C Kappelman, M AF Long, Millie Crandall, Wallace Leibowitz, Ian Duffy, Lynn del Rosario, Fernando Kim, Sandra Integlia, Mark Berman, James Grunow, John Colletti, Richard Schoen, Bess Patel, Ashish Baron, Howard Israel, Esther Russell, George Ali, Sabina Herfarth, Hans Martin, Christopher Kappelman, Michael TI The Prevalence and Epidemiology of Overweight and Obesity in Children with Inflammatory Bowel Disease SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 75th Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 15-20, 2010 CL San Antonio, TX SP Amer Coll Gastroenterol C1 [Long, Millie; Herfarth, Hans] Univ N Carolina, Dept Med, Div Gastroenterol & Hepatol, Chapel Hill, NC USA. [Martin, Christopher] Ctr Gastrointestinal Biol & Dis, Chapel Hill, NC USA. [Crandall, Wallace] Nationwide Childrens Hosp, Div Gastroenterol, Columbus, OH USA. [Leibowitz, Ian; Duffy, Lynn] Inova Pediat Digest Dis Ctr, Fairfax, VA USA. [del Rosario, Fernando] Nemours Childrens Clin, Orlando, FL USA. [Kim, Sandra; Kappelman, Michael] Univ N Carolina, Dept Pediat, Div Gastroenterol & Hepatol, Chapel Hill, NC USA. [Integlia, Mark] Maine Med Ctr, Dept Pediat, Portland, ME 04102 USA. [Berman, James] Loyola Univ, Dept Pediat, Chicago, IL 60611 USA. [Grunow, John] Univ Oklahoma, Dept Pediat, Oklahoma City, OK USA. [Colletti, Richard] Univ Vermont, Dept Pediat, Burlington, VT USA. [Schoen, Bess] Emory Univ, Dept Pediat, Atlanta, GA 30322 USA. [Patel, Ashish] UT SW Med Ctr, Div Pediat Gastroenterol, Dallas, TX USA. [Patel, Ashish] Childrens Med Ctr, Dallas, TX 75235 USA. [Baron, Howard] Pediat Gastroenterol & Nutr Associates, Las Vegas, NV USA. [Israel, Esther; Russell, George] Massachusetts Gen Hosp, Dept Pediat, Boston, MA 02114 USA. [Ali, Sabina] Childrens Hosp & Res Ctr, Div Gastroenterol, Oakland, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2010 VL 105 SU 1 MA 1464 BP S544 EP S544 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 663VG UT WOS:000282917701651 ER PT J AU Patel, M Shah, S Leleiko, N Lidofsky, S Bright, R Grabert, S Law, M Moniz, H Bancroft, B Suorsa, K Harris, A Vancura, J Kalasapudi, B Cole, E Sands, B AF Patel, Mitul Shah, Samir Leleiko, Neal Lidofsky, Sheldon Bright, Renee Grabert, Stacey Law, Meaghan Moniz, Heather Bancroft, Barbara Suorsa, Kristina Harris, Adam Vancura, Jennifer Kalasapudi, Bharati Cole, Elisabeth Sands, Bruce TI Presenting Symptoms at Diagnosis of Crohn's Disease and Ulcerative Colitis: Results from the Ocean State Crohn's and Colitis Area Registry (OSCCAR) SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 75th Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 15-20, 2010 CL San Antonio, TX SP Amer Coll Gastroenterol C1 [Patel, Mitul; Shah, Samir; Leleiko, Neal; Lidofsky, Sheldon; Bright, Renee; Law, Meaghan; Moniz, Heather; Bancroft, Barbara; Suorsa, Kristina; Harris, Adam; Vancura, Jennifer; Kalasapudi, Bharati] Lifespan, Providence, RI USA. [Patel, Mitul; Shah, Samir; Leleiko, Neal; Lidofsky, Sheldon; Bright, Renee; Law, Meaghan; Moniz, Heather; Bancroft, Barbara; Suorsa, Kristina; Harris, Adam; Vancura, Jennifer; Kalasapudi, Bharati] Brown Univ, Providence, RI 02912 USA. [Grabert, Stacey; Cole, Elisabeth] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sands, Bruce] Mt Sinai Sch Med, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2010 VL 105 SU 1 MA 1174 BP S426 EP S427 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 663VG UT WOS:000282917701364 ER PT J AU Raizner, A Gromski, M Goodman, A Matthes, K Ho, S Robbins, D Chuttani, R Brugge, W Sawhney, M Lee, Y Stavropoulos, S Maydeo, A Guthrie, W Gress, F AF Raizner, Aileen Gromski, Mark Goodman, Adam Matthes, Kai Ho, Sammy Robbins, David Chuttani, Ram Brugge, William Sawhney, Mandeep Lee, Young Stavropoulos, Stavros Maydeo, Amit Guthrie, Walter Gress, Frank TI Evaluation of a New Endoscopic Ultrasound (EUS) Simulator (EASIE-RT (TM)) for Teaching Basic and Advanced Skills of EUS SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 75th Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 15-20, 2010 CL San Antonio, TX SP Amer Coll Gastroenterol C1 [Raizner, Aileen; Goodman, Adam; Lee, Young; Guthrie, Walter; Gress, Frank] Suny Downstate Med Ctr, Brooklyn, NY 11203 USA. [Gromski, Mark; Matthes, Kai; Chuttani, Ram; Sawhney, Mandeep] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Ho, Sammy] Montefiore Med Ctr, Bronx, NY 10467 USA. [Robbins, David] Lenox Hill Hosp, New York, NY 10021 USA. [Brugge, William] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Stavropoulos, Stavros] Winthrop Univ Hosp, Mineola, NY 11501 USA. [Maydeo, Amit] Inst Adv Endoscopy, Bombay, Maharashtra, India. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2010 VL 105 SU 1 MA 1360 BP S503 EP S504 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 663VG UT WOS:000282917701549 ER PT J AU Richter, J Kushkuley, S Oster, G AF Richter, James Kushkuley, Sophie Oster, Gerry TI Treatment of Newly Diagnosed Ulcerative Proctitis in Community-Based Practice SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 75th Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 15-20, 2010 CL San Antonio, TX SP Amer Coll Gastroenterol C1 [Richter, James] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. [Kushkuley, Sophie; Oster, Gerry] Policy Anal Inc, Brookline, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2010 VL 105 SU 1 MA 1242 BP S456 EP S456 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 663VG UT WOS:000282917701433 ER PT J AU Sandborn, W Rutgeerts, P Reinisch, W Esser, D Wang, Y Lang, YH Marano, C Strauss, R Oddens, B Feagan, B Hanauer, S Lichtenstein, G Present, D Sands, B Colombel, JF AF Sandborn, William Rutgeerts, Paul Reinisch, Walter Esser, Dirk Wang, Y. Lang, Yinghua Marano, Colleen Strauss, Richard Oddens, Bjorn Feagan, Brian Hanauer, Stephen Lichtenstein, Gary Present, Daniel Sands, Bruce Colombel, Jean-Frederic TI Mucosal Healing in Patients with Ulcerative Colitis Associates with a Reduced Colectomy Risk, High Incidence of Symptomatic Remission, and Corticosteroid-Free State SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 75th Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 15-20, 2010 CL San Antonio, TX SP Amer Coll Gastroenterol C1 [Sandborn, William] Mayo Clin, Rochester, MN USA. [Rutgeerts, Paul] U Hosp Gasthuisberg, Louvain, Belgium. [Reinisch, Walter] U Hosp Vienna, Vienna, Austria. [Esser, Dirk] Centocor BV, Leiden, Netherlands. [Wang, Y.; Oddens, Bjorn] Schering Plough Corp, Kenilworth, NJ 07033 USA. [Lang, Yinghua; Marano, Colleen; Strauss, Richard] Centocor R&D, Malvern, PA USA. [Feagan, Brian] Robarts Res Inst, London, ON N6A 5C1, Canada. [Hanauer, Stephen] U Chicago, Chicago, IL USA. [Lichtenstein, Gary] U Penn, Philadelphia, PA USA. [Present, Daniel] Mt Sinai Med Ctr, New York, NY 10029 USA. [Sands, Bruce] Harvard Univ, Sch Med, Mass Gen Hosp, Boston, MA USA. [Colombel, Jean-Frederic] CHRU, Lille, France. RI Feagan, Brian/M-4283-2015 NR 0 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2010 VL 105 SU 1 MA 1200 BP S438 EP S439 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 663VG UT WOS:000282917701391 ER PT J AU Shah, S Leleiko, N Lidofsky, S Bright, R Grabert, S Law, M Moniz, H Bancroft, B Suorsa, K Patel, M Vancura, J Harris, A Kalasapudi, B Cole, E Sands, B AF Shah, Samir Leleiko, Neal Lidofsky, Sheldon Bright, Renee Grabert, Stacey Law, Meaghan Moniz, Heather Bancroft, Barbara Suorsa, Kristina Patel, Mitul Vancura, Jennifer Harris, Adam Kalasapudi, Bharati Cole, Elisabeth Sands, Bruce TI Ocean State Crohn's and Colitis Area Registry (OSCCAR): Incidence of Crohn's Disease and Ulcerative Colitis in a Prospective, Population-Based Inception Cohort in Rhode Island SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 75th Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 15-20, 2010 CL San Antonio, TX SP Amer Coll Gastroenterol C1 [Shah, Samir; Leleiko, Neal; Lidofsky, Sheldon; Bright, Renee; Law, Meaghan; Moniz, Heather; Bancroft, Barbara; Suorsa, Kristina; Patel, Mitul; Vancura, Jennifer; Harris, Adam; Kalasapudi, Bharati] Lifespan, Providence, RI USA. [Shah, Samir; Leleiko, Neal; Lidofsky, Sheldon; Bright, Renee; Law, Meaghan; Moniz, Heather; Bancroft, Barbara; Suorsa, Kristina; Patel, Mitul; Vancura, Jennifer; Harris, Adam; Kalasapudi, Bharati] Brown Univ, Providence, RI 02912 USA. [Grabert, Stacey; Cole, Elisabeth] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Sands, Bruce] Mt Sinai Sch Med, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2010 VL 105 SU 1 MA 1172 BP S425 EP S426 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 663VG UT WOS:000282917701362 ER PT J AU Sun, S Spiegel, B Mody, R Dabbous, F Dabbous, O Chey, W AF Sun, Shawn Spiegel, Brennan Mody, Reema Dabbous, Firas Dabbous, Omar Chey, William TI Economic and Humanistic Burden of Chronic Constipation SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Meeting Abstract CT 75th Annual Scientific Meeting of the American-College-of-Gastroenterology CY OCT 15-20, 2010 CL San Antonio, TX SP Amer Coll Gastroenterol C1 [Sun, Shawn; Mody, Reema; Dabbous, Firas; Dabbous, Omar] Takeda Pharmaceut N Amer, Deerfield, IL USA. [Spiegel, Brennan] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. [Chey, William] Univ Michigan Hlth Syst, Ann Arbor, MI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD OCT PY 2010 VL 105 SU 1 MA 1081 BP S391 EP S391 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 663VG UT WOS:000282917701271 ER PT J AU Copeland, LA Parchman, ML Zeber, JE Lawrence, VA Downs, JR Miller, AL AF Copeland, Laurel A. Parchman, Michael L. Zeber, John E. Lawrence, Valerie A. Downs, John R. Miller, Alexander L. TI Prediabetes Assessment and Follow-up in Older Veterans With Schizophrenia SO AMERICAN JOURNAL OF GERIATRIC PSYCHIATRY LA English DT Article DE Mortality; prediabetes; schizophrenia; veterans ID ANTIPSYCHOTIC-DRUGS; DIABETES-MELLITUS; CARDIOVASCULAR-DISEASE; METABOLIC SYNDROME; GLUCOSE-TOLERANCE; EXCESS MORTALITY; HEALTH-SERVICES; PRIMARY-CARE; RISK; WEIGHT AB Objectives: Assess glycemic monitoring and follow-up. Design: Retrospective study using administrative data (October 2001-September 2005). Setting: Veterans Health Administration. Participants: A nationwide sample of 39,226 outpatients aged 50 years or older with schizophrenia. Patients had no diagnosis or medications for diabetes at baseline. Measurements: Hemoglobin A1c tests; blood glucose tests with same-day low-density lipoprotein to approximate fasting glucose. Glycemic tests were combined to indicate a) prediabetic dysglycemia (100-125 mg/dL proxy fasting glucose or 5.8%-6.4% hemoglobin A1c) and b) diabetic dysglycemia (>= 126 proxy fasting glucose or >= 6.5% A1c). Results: Approximately one-third of patients (32%; 12,587) had proxy fasting blood glucose or A1c tests in 2002; multiple tests were rare. The proportion tested increased to 40% by 2005. Test results suggested prediabetic dysglycemia for 5,345 tested patients (42% of those tested) and diabetic dysglycemia for 1,287 tested patients (10%) at baseline. In multivariate regression models, glycemic testing was associated with dyslipidemia, hypertension, and younger age. Dysglycemia was associated with hypertension, dyslipidemia, and older age. Follow-up treatment/diagnosis of diabetes occurred for 8% of patients (11% of those tested) and was associated with baseline dysglycemia, hypertension, and younger age. Mortality (15% during the 4-year study) was higher among untested and untreated patients. Conclusions: Dysglycemia was prevalent among older patients with schizophrenia, although monitoring and follow-up were uncommon. Follow-up treatment correlated with survival. Despite evident utility of testing, few at-risk patients with schizophrenia were adequately monitored, diagnosed, or treated for dysglycemia. (Am J Geriatr Psychiatry 2010; 18:887-896) C1 [Copeland, Laurel A.; Zeber, John E.; Miller, Alexander L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX 78229 USA. [Parchman, Michael L.] Univ Texas Hlth Sci Ctr San Antonio, Dept Family & Community Med, San Antonio, TX 78229 USA. [Lawrence, Valerie A.; Downs, John R.] Univ Texas Hlth Sci Ctr San Antonio, Dept Med, San Antonio, TX 78229 USA. RP Copeland, LA (reprint author), VERDICT Res, S Texas Vet HCS, 7400 Merton Minter 11C6, San Antonio, TX 78229 USA. EM LaurelACopeland@gmail.com OI Parchman, Michael/0000-0001-7129-2889; Copeland, Laurel/0000-0002-9478-0209 FU Department of Veterans Affairs [IIR-05-326]; VERDICT Research Center; University of Texas Health Science Center at San Antonio; Copeland as PI: VA HSRD; Hogg Fndn/UT-Austin; Copeland as co-I: VA HSRD; VA VISN 17; NIH; Dept of Defense; Parchman as PI: VA/HSRD; NIDDK; Parchman as co-I: VA HSRD; Lawrence as PI: VA/HSRD; Lawrence as co-I: VHA; Zeber as PI: VA HSRD; PhRMA Fndn; UTHSCSA Training Pgm; Zeber as co-I: VA HSRD; Downs as PI: none Downs as co-I: VA/HSRD; NINR; Miller as PI: AstraZeneca; Pfizer Organon; UNC/NIMH; Glaxo Smith Kline; Pfizer; Sanofi Aventis; Janssen; Miller as co-I: VA HSRD; Research Foundation for Mental Hygiene New York; CME, Inc. Orlando, FL; France Foundation Atlanta, GA; Organon (Advisory Board) Parsippany, NJ; Dainippon Sumitomo (Advisory Board) Chicago; Eli Lilly (Advisory Board) Scottsdale, AZ; AstraZeneca (Advisory Board) Baltimore; CME Outfitters Washington, DC; Research Foundation for Mental Hygiene; VA San Antonio, TX; Comprehensive Neuroscience online survey; NCME, Inc. French Camp, CA; State of Maryland Baltimore; NCME, Inc. Smithville, TX; NCME, Inc. Reno, NV; International Congress on Schizophrenia Research San Diego, CA; VA HSRD FX This work was supported by the Department of Veterans Affairs (Grant # IIR-05-326; PI: Copeland) with additional support from VERDICT Research Center and the University of Texas Health Science Center at San Antonio.; Funding Details: Copeland as PI: VA HSR&D 2009-2010 $50,300; VA HSR&D 2006-2008 $300,000; VA HSR&D 2006-2009 $273,200; VA HSR&D 2008 $35,600; Hogg Fndn/UT-Austin 2009-2010 $14,995; Copeland as co-I: VA HSR&D 2009-2010 $223,600; VA HSR&D 2006-2010 $725,500; VA HSR&D 2003-2008 $735,400; VA VISN 17 2005-2008 $586,422; VA VISN 17 20052008 $736,990; VA HSR&D 2006-2009 $518,100; NIH 2007-2010 $323,538; Dept of Defense 2008-2013 $25,000,000.; Parchman as PI: VA/HSR&D 2009-2012 $834,600; NIH 2007-2012 $2,050,750; NIDDK 2004-2007 $301,500; Parchman as co-I: VA HSR&D 2008 to 2009 $146,500; VA/HSR&D 2006-2009 $271,300; VA/HSR&D 2003-2008 $735,400; NIH 2008-2013 $1,500,000; VA/HSR&D 2007-2008 $74,500; NIH 2006-2011 400,000; Lawrence as PI: VA/HSR&D 2007-2012 $734,050; VA/HSR&D 2003-2008 $735,400; Lawrence as co-I: VHA 2007-2009 $90,000; VA/HSR&D 2006-2009 $273,200; VA/HSR&D 2008-2008 $84,800; VA/HSR&D 2008-2008 $35,600; Zeber as PI: VA HSR&D 2009 $50,000; VA VISN 17 2008-2009 $100,000; PhRMA Fndn 2007-2008 $60,000; UTHSCSA Training Pgm 50% salary support 2006-2008; Zeber as co-I: VA HSR&D 2008 $35,600; VA HSR&D 2009-2010 $141,000; VA HSR&D 2009-2010 $50,300; VA HSR&D 2009-2010 $223,600; VA HSR&D 2006-2010 $725,500; VA HSR&D 2003-2008 $735,400; VA HSR&D 2006-2009 $273,200.; Downs as PI: none Downs as co-I: VA/HSR&D 2007-2010 $468,300; VA/HSR&D 2008-2008 $84,800; NINR 2007-2010 $788,497; Miller as PI: AstraZeneca 2007-2009 $35,256; Pfizer Organon 2007-2009 $36,988; UNC/NIMH 2007-2009 $150,030; UNC/NIMH 2007-2009 $33,750; UNC/NIMH 2007-2009 $80,360; UNC/NIMH 2009 $20,090; Glaxo Smith Kline 2007 $9,582; Pfizer 2007-2009 $160,000; Sanofi Aventis 2009 $89,916; Janssen 2008 $9,036; NIMH 2006-2011 $2,297,435; Miller as co-I: VA HSR&D 20062009 $273,200; Janssen 2008 $35,000; NIMH 2006-2011 $2,251,596; NIMH 2008-2013 $2,523,247; Miller Honoraria: Research Foundation for Mental Hygiene New York 08-30-07 $1,000; CME, Inc. Orlando, FL 10-12-07 $2,500; France Foundation Atlanta, GA 10-09-07 $1,500; Organon (Advisory Board) Parsippany, NJ 10-25-07 $3,000; Dainippon Sumitomo (Advisory Board) Chicago 10-26-07 $3,000; Eli Lilly (Advisory Board) Scottsdale, AZ 11-01-07$1,500; AstraZeneca (Advisory Board) Baltimore 11-02-07 $2,750 CME Outfitters Washington, DC 11-07-07 $5,000; Research Foundation for Mental Hygiene 09-07-08 to 10-21-08 $2,500; VA San Antonio, TX 03-18-08 $300; Comprehensive Neuroscience online survey 05-30-08 $250; NCME, Inc. French Camp, CA 10-22-08 $2,000; State of Maryland Baltimore 11-12-08 $200; NCME, Inc. Smithville, TX 11-18-08 $2,000; NCME, Inc. Reno, NV 12-17-08 $2,000; International Congress on Schizophrenia Research San Diego, CA 03-31-09 $1,000. NR 36 TC 14 Z9 14 U1 2 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 OCT PY 2010 VL 18 IS 10 BP 887 EP 896 DI 10.1097/JGP.0b013e3181e56cdc PG 10 WC Geriatrics & Gerontology; Gerontology; Psychiatry SC Geriatrics & Gerontology; Psychiatry GA 653WP UT WOS:000282128900004 PM 20808110 ER PT J AU Davids, MS Murali, MR Kuter, DJ AF Davids, Matthew S. Murali, Mandakolathur R. Kuter, David J. TI Serum free light chain analysis SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; STEM-CELL TRANSPLANTATION; INDEPENDENT RISK-FACTOR; MULTIPLE-MYELOMA; UNDETERMINED SIGNIFICANCE; MONOCLONAL GAMMOPATHY; IMMUNOGLOBULIN; AMYLOIDOSIS; URINE; PROGRESSION AB In a variety of hematologic malignancies, immunoglobulin light chains (LC) are overproduced clonally and circulate without being linked by disulphide bonds to the immunoglobulin heavy chain. The recent development of a robust assay known as kappa and gamma "free'' LC (FLC) to quantify the levels of these unbound LC in the serum, and thereby determine their ratio, has led to an explosion of studies that demonstrate its utility in a wide range of hematologic disorders. This article summarizes laboratory testing for serum FLC, with a particular focus on clinical applications for the test. Am. J. Hematol. 85:787-790, 2010. (C) 2010 Wiley-Liss, Inc. C1 [Davids, Matthew S.; Kuter, David J.] Massachusetts Gen Hosp, Ctr Hematol, Boston, MA 02114 USA. [Davids, Matthew S.; Murali, Mandakolathur R.; Kuter, David J.] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. [Murali, Mandakolathur R.] Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA. RP Kuter, DJ (reprint author), Massachusetts Gen Hosp, Ctr Hematol, 55 Fruit St, Boston, MA 02114 USA. EM dkuter@partners.org NR 33 TC 18 Z9 18 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD OCT PY 2010 VL 85 IS 10 BP 787 EP 790 DI 10.1002/ajh.21815 PG 4 WC Hematology SC Hematology GA 661RD UT WOS:000282744500010 PM 20721885 ER PT J AU Williams, DA Porter, ES Lux, SE Grier, HE Mack, JW Orkin, SH AF Williams, David A. Porter, Elise S. Lux, Samuel E. Grier, Holcombe E. Mack, Jennifer W. Orkin, Stuart H. TI Training program in cancer and blood diseases: Pediatric Hematology/Oncology Fellowship Program, Children's Hospital Boston/Dana-Farber Cancer Institute SO AMERICAN JOURNAL OF HEMATOLOGY LA English DT Article C1 [Williams, David A.; Porter, Elise S.; Lux, Samuel E.] Harvard Univ, Sch Med, Childrens Hosp Boston, Div Hematol Oncol, Boston, MA 02115 USA. [Grier, Holcombe E.; Mack, Jennifer W.; Orkin, Stuart H.] Harvard Univ, Sch Med, Dept Pediat Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Williams, DA (reprint author), Harvard Univ, Sch Med, Childrens Hosp Boston, Div Hematol Oncol, 300 Longwood Ave,Karp 08125-3, Boston, MA 02115 USA. EM dawilliams@childrens.harvard.edu NR 0 TC 1 Z9 1 U1 1 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0361-8609 J9 AM J HEMATOL JI Am. J. Hematol. PD OCT PY 2010 VL 85 IS 10 BP 793 EP 794 DI 10.1002/ajh.21816 PG 2 WC Hematology SC Hematology GA 661RD UT WOS:000282744500013 PM 20730793 ER PT J AU Sembajwe, G Quinn, M Kriebel, D Stoddard, A Krieger, N Barbeau, E AF Sembajwe, Grace Quinn, Margaret Kriebel, David Stoddard, Anne Krieger, Nancy Barbeau, Elizabeth TI The Influence of Sociodemographic Characteristics on Agreement Between Self-Reports and Expert Exposure Assessments SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE exposure assessment; occupational epidemiology; job exposure matrix; agreement; discord; higher estimation; lower estimation ID OCCUPATIONAL CASE-CONTROL; INDUSTRIAL-HYGIENE; RETROSPECTIVE ASSESSMENT; INTERRATER AGREEMENT; PESTICIDE EXPOSURE; MULTIPLE RATERS; SOCIAL HAZARDS; RATINGS; HEALTH; EPIDEMIOLOGY AB Background Often in exposure assessment for epidemiology, there are no highly accurate exposure data and different measurement methods are considered. The objective of this study was to use various statistical techniques to explore agreement between individual reports and expert ratings of workplace exposures in several industries and investigate the sociodemographic influences on this agreement. Methods A cohort of 1,282 employees at 4 industries/14 worksites answered questions on workplace physical, chemical, and psychosocial exposures over the past 12 months. Occupational hygienists constructed job exposure matrices (JEMs) based on worksite walkthrough exposure evaluations. Worker self-reports were compared with the JEMs using multivariable analyses to explore discord. Results There was poor agreement between the self-reported and expert exposure assessments, but there was evidence that agreement was modified by sociodemographic characteristics. Several characteristics including gender, age, race/ethnicity, hourly wage and nativity strongly affected the degree of discord between self-reports and expert raters across a wide array of different exposures. Conclusions Agreement between exposure assessment tools may be affected by sociodemographic characteristics. This study is cross-sectional and therefore, a snapshot of potential exposures in the workplace. Nevertheless, future studies should take into account the social contexts within which workplace exposures occur. Am. J. Ind. Med. 53: 1019-1031, 2010. (C) 2010 Wiley-Liss, Inc. C1 [Sembajwe, Grace; Krieger, Nancy; Barbeau, Elizabeth] Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Sembajwe, Grace; Quinn, Margaret; Kriebel, David] Univ Massachusetts Lowell, Dept Work Environm, Lowell, MA USA. [Sembajwe, Grace; Barbeau, Elizabeth] Dana Farber Canc Inst, Ctr Community Based Res, Boston, MA 02115 USA. [Stoddard, Anne] New England Res Inst, Dept Stat Anal & Res, Watertown, MA 02172 USA. RP Sembajwe, G (reprint author), Harvard Univ, Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. EM grace_sembajwe@dfci.harvard.edu FU NIOSH [R01 OH07366-01, R01 OH07366-01S] FX Contract grant sponsor: NIOSH; Contract grant numbers: R01 OH07366-01, R01 OH07366-01S. NR 57 TC 5 Z9 5 U1 0 U2 7 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD OCT PY 2010 VL 53 IS 10 BP 1019 EP 1031 DI 10.1002/ajim.20821 PG 13 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 657MR UT WOS:000282417300008 PM 20306494 ER PT J AU Gellad, WF Good, CB Lowe, JC Donohue, JM AF Gellad, Walid F. Good, Chester B. Lowe, John C. Donohue, Julie M. TI Variation in Prescription Use and Spending for Lipid-Lowering and Diabetes Medications in the Veterans Affairs Healthcare System SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID GEOGRAPHIC-VARIATION; UNITED-STATES; DRUG PRICES; QUALITY; PREVALENCE; HOSPITALS; DECISION; TRIALS; SAFETY; SAMPLE AB Objectives: To examine variation in outpatient prescription use and spending for hyperlipidemia and diabetes mellitus in the Veterans Affairs Healthcare System (VA) and its association with quality measures for these conditions. Study Design: Cross-sectional. Methods: We compared outpatient prescription use, spending, and quality of care across 135 VA medical centers (VAMCs) in fiscal year 2008, including 2.3 million patients dispensed lipid-lowering medications and 981,031 patients dispensed diabetes medications. At each facility, we calculated VAMC-level cost per patient for these medications, the proportion of patients taking brand-name drugs, and Healthcare Effectiveness Data and Information Set (HEDIS) scores for hyperlipidemia (low-density lipoprotein cholesterol level <100 mg/dL) and for diabetes (glycosylated hemoglobin level >9% or not measured). Results: The median cost per patient for lipid-lowering agents in fiscal year 2008 was $49.60 and varied from $39.68 in the least expensive quartile of VAMCs to $69.57 in the most expensive quartile (P < .001). For diabetes agents, the median cost per patient was $158.34 and varied from $123.34 in the least expensive quartile to $198.31 in the most expensive quartile (P < .001). The proportion of patients dispensed brand-name oral drugs among these classes in the most expensive quartile of VAMCs was twice that in the least expensive quartile (P < .001). There was no correlation between VAMC-level prescription spending and performance on HEDIS measures for lipid-lowering drugs (r = 0.12 and r = 0.07) or for diabetes agents (r = -0.10). Conclusions: Despite the existence of a closely managed formulary, significant variation in prescription spending and use of brand-name drugs exists in the VA. Although we could not explicitly risk-adjust, there appears to be no relationship between prescription spending and quality of care. (Am J Manag Care. 2010;16(10):741-750) C1 [Gellad, Walid F.] VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Dept Vet Affairs Med Ctr, Pittsburgh, PA 15206 USA. [Good, Chester B.] VA Pittsburgh Healthcare Syst, Ctr Medicat Safety, Pittsburgh, PA 15206 USA. [Gellad, Walid F.; Good, Chester B.] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. [Lowe, John C.] Univ Pittsburgh, Dept Pharm, Pittsburgh, PA USA. [Donohue, Julie M.] Univ Pittsburgh, Dept Hlth Policy & Management, Pittsburgh, PA USA. [Gellad, Walid F.] RAND Corp, Pittsburgh, PA USA. [Lowe, John C.] Vet Hlth Adm, Pharm Benefits Mangement Serv, Washington, DC USA. RP Gellad, WF (reprint author), VA Pittsburgh Healthcare Syst, Ctr Hlth Equ Res & Promot, Dept Vet Affairs Med Ctr, 7180 Highland Dr, Pittsburgh, PA 15206 USA. EM walid.gellad@va.gov OI Donohue, Julie/0000-0003-2418-6017 FU VA Pittsburgh Healthcare System; National Center for Research Resources, National Institutes of Health Roadmap for Medical Research [KL2 RR024154] FX This study is the result of work supported by resources from the VA Pittsburgh Healthcare System. Dr Donohue was supported by grant KL2 RR024154 from the National Center for Research Resources, a component of the National Institutes of Health Roadmap for Medical Research. NR 38 TC 7 Z9 7 U1 0 U2 5 PU MANAGED CARE & HEALTHCARE COMMUNICATIONS LLC PI PLAINSBORO PA 666 PLAINSBORO RD, STE 300, PLAINSBORO, NJ 08536 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD OCT PY 2010 VL 16 IS 10 BP 741 EP 750 PG 10 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 678SO UT WOS:000284100900006 PM 20964470 ER PT J AU Kim, H Ross, JS Melkus, GD Zhao, ZL Boockvar, K AF Kim, Hongsoo Ross, Joseph S. Melkus, Gail D. Zhao, Zhonglin Boockvar, Kenneth TI Scheduled and Unscheduled Hospital Readmissions Among Patients With Diabetes SO AMERICAN JOURNAL OF MANAGED CARE LA English DT Article ID REHOSPITALIZATIONS; MEDICINE; QUALITY; RATES; CARE AB Objectives: To describe rates of scheduled and unscheduled readmissions among midlife and older patients with diabetes and to examine associated socioeconomic and clinical factors. Study Design: Population-based data set study. Methods: Using the 2006 California State Inpatient Dataset, we identified 124,967 patients 50 years or older with diabetes who were discharged from acute care hospitals between April and September 2006 and examined readmissions in the 3 months following their index hospitalizations. Results: About 26.3% of patients were readmitted within the 3-month period following their index hospitalizations, 87.2% of which were unscheduled readmissions. Patients with unscheduled readmissions were more likely to have a higher comorbidity burden, be members of racial/ethnic minority groups with public insurance, and live in lower-income neighborhoods. Having a history of hospitalization in the 3 months preceding the index hospitalization was also a strong predictor of unscheduled readmissions. Almost one-fifth of unscheduled readmissions (constituting approximately 27,500 inpatient days and costing almost $72.7 million) were potentially preventable based on definitions of Prevention Quality Indicators by the Agency for Healthcare Research and Quality. Scheduled readmissions were less likely to occur among patients 80 years or older, the uninsured, and those with an unscheduled index hospitalization. Conclusions: The predictors of scheduled and unscheduled readmissions are different. Transition care to prevent unscheduled readmissions in acutely ill patients with diabetes may help reduce rates, improving care. Further studies are needed on potential disparities in scheduled readmissions. (Am J Manag Care. 2010;16(10):760-767) C1 [Kim, Hongsoo] Seoul Natl Univ, Grad Sch Publ Hlth, Seoul 151742, South Korea. [Kim, Hongsoo] Seoul Natl Univ, Inst Hlth & Environm, Seoul 151742, South Korea. [Ross, Joseph S.; Boockvar, Kenneth] James J Peters VA Med Ctr, Bronx, NY USA. [Ross, Joseph S.; Boockvar, Kenneth] Mt Sinai Sch Med, New York, NY USA. [Melkus, Gail D.] NYU, Coll Nursing, New York, NY USA. [Zhao, Zhonglin] NYU, Coll Dent, New York, NY USA. RP Kim, H (reprint author), Seoul Natl Univ, Grad Sch Publ Hlth, 599 Kwanak Ro, Seoul 151742, South Korea. EM hk65.snu@gmail.com OI Boockvar, Kenneth/0000-0003-1165-5558 FU NIA NIH HHS [K08 AG032886] NR 24 TC 23 Z9 23 U1 1 U2 4 PU MANAGED CARE & HEALTHCARE COMMUNICATIONS LLC PI PLAINSBORO PA 666 PLAINSBORO RD, STE 300, PLAINSBORO, NJ 08536 USA SN 1088-0224 J9 AM J MANAG CARE JI Am. J. Manag. Care PD OCT PY 2010 VL 16 IS 10 BP 760 EP 767 PG 8 WC Health Care Sciences & Services; Health Policy & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 678SO UT WOS:000284100900008 PM 20964472 ER PT J AU Kantarci, S Ackerman, KG Russell, MK Longoni, M Sougnez, C Noonan, KM Hatchwell, E Zhang, XY Pieretti-Vanmarcke, R Anyane-Yeboa, K Dickman, P Wilson, J Donahoe, PK Pober, BR AF Kantarci, Sibel Ackerman, Kate G. Russell, Meaghan K. Longoni, Mauro Sougnez, Carrie Noonan, Kristin M. Hatchwell, Eli Zhang, Xiaoyun Pieretti-Vanmarcke, Rafael Anyane-Yeboa, Kwame Dickman, Paul Wilson, Jay Donahoe, Patricia K. Pober, Barbara R. TI Characterization of the Chromosome 1q41q42.12 region, and the Candidate Gene DISP1, in Patients With CDH SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE congenital diaphragmatic hernia (CDH); chromosome 1q41q42 deletion; microdeletion; MLPA; pyrosequencing; Sonic Hedgehog (SHH) pathway; pleuroperitoneal fold (PPF) ID CONGENITAL DIAPHRAGMATIC-HERNIA; COMPARATIVE GENOMIC HYBRIDIZATION; HLX HOMEOBOX GENE; SONIC HEDGEHOG; MOUSE; EXPRESSION; LUNG; IDENTIFICATION; MORPHOGENESIS; PATHOGENESIS AB Cytogenetic and molecular cytogenetic studies demonstrate association between congenital diaphragmatic hernia (CDH) and chromosome 1q41q42 deletions. In this study, we screened a large CDH cohort (N = 179) for microdeletions in this interval by the multiplex ligation-dependent probe amplification (MLPA) technique, and also sequenced two candidate genes located therein, dispatched 1 (DISP1) and homo sapiens H2.0-like homeobox (HLX). MLPA analysis verified deletions of this region in two cases, an unreported patient with a 46,XY,del(1)-(q41q42.13) karyotype and a previously reported patient with a Fryns syndrome phenotype [Kantarci et al., 2006]. HLXsequencing showed a novel but maternally inherited single nucleotide variant (c.27C>G) in a patient with isolated CDH, while DISP1 sequencing revealed a mosaic de novo heterozygous substitution (c.4412C>G; p.Ala1471Gly) in a male with a left-sided Bochdalek hernia plus multiple other anomalies. Pyrosequencing demonstrated the mutant allele was present in 43%, 12%, and 4.5% of the patient's lymphoblastoid, peripheral blood lymphocytes, and saliva cells, respectively. We examined Disp1 expression at day E11.5 of mouse diaphragm formation and confirmed its presence in the pleuroperitoneal fold, as well as the nearby lung which also expresses Sonic hedgehog (Shh). Our report describes the first de novo DISP1 point mutation in a patient with complex CDH. Combining this finding with Disp1 embryonic mouse diaphragm and lung tissue expression, as well as previously reported human chromosome 1q41q42 aberrations in patients with CDH, suggests that DISP1 may warrant further consideration as a CDH candidate gene. (C) 2010 Wiley-Liss, Inc. C1 [Kantarci, Sibel; Russell, Meaghan K.; Longoni, Mauro; Noonan, Kristin M.; Pieretti-Vanmarcke, Rafael; Donahoe, Patricia K.; Pober, Barbara R.] Massachusetts Gen Hosp, Pediat Surg Res Lab, Boston, MA 02114 USA. [Kantarci, Sibel; Longoni, Mauro; Pieretti-Vanmarcke, Rafael; Wilson, Jay; Donahoe, Patricia K.; Pober, Barbara R.] Harvard Univ, Sch Med, Boston, MA USA. [Ackerman, Kate G.; Zhang, Xiaoyun] Univ Rochester, Dept Pediat, Rochester, NY USA. [Ackerman, Kate G.; Zhang, Xiaoyun] Univ Rochester, Dept Biomed Genet, Rochester, NY USA. [Sougnez, Carrie] Broad Inst, Cambridge, MA USA. [Hatchwell, Eli] SUNY Stony Brook, Dept Pathol, Stony Brook, NY 11794 USA. [Anyane-Yeboa, Kwame] Columbia Univ, Med Ctr, Dept Genet, New York, NY USA. [Dickman, Paul] Phoenix Childrens Hosp, Dept Pathol, Phoenix, AZ USA. [Wilson, Jay; Pober, Barbara R.] Childrens Hosp, Dept Surg, Boston, MA 02115 USA. RP Pober, BR (reprint author), Ctr Human Genet, Simches Res Bldg,185 Cambridge St,Rm 222, Boston, MA 02115 USA. EM barbara.pober@childrens.harvard.edu RI Longoni, Mauro/I-2526-2013 FU National Institutes of Health [R01 HD55150-01]; Broad Institute SPARC; MGH Austen and McBride Funds FX Grant sponsor: National Institutes of Health; Grant number: R01 HD55150-01; Grant sponsor: Broad Institute SPARC Grant; Grant sponsor: MGH Austen and McBride Funds. NR 43 TC 20 Z9 21 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD OCT PY 2010 VL 152A IS 10 BP 2493 EP 2504 DI 10.1002/ajmg.a.33618 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 666GX UT WOS:000283103700009 PM 20799323 ER PT J AU Singh, H Petersen, LA Thomas, EJ Wilson, L Sittig, DF AF Singh, Hardeep Petersen, Laura A. Thomas, Eric J. Wilson, Lindsey Sittig, Dean F. TI Notification of Abnormal and Critical Values: The Road Ahead Reply SO AMERICAN JOURNAL OF MEDICINE LA English DT Letter C1 [Singh, Hardeep; Petersen, Laura A.; Wilson, Lindsey] Baylor Coll Med, Houston VA Hlth Serv Res & Dev Ctr Excellence, Houston, TX 77030 USA. [Singh, Hardeep; Petersen, Laura A.; Wilson, Lindsey] Baylor Coll Med, Ctr Inquiry Improve Outpatient Safety Effect Elec, Michael E DeBakey Vet Affairs Med Ctr, Houston, TX 77030 USA. [Singh, Hardeep; Petersen, Laura A.; Wilson, Lindsey] Baylor Coll Med, Sect Hlth Serv Res, Dept Med, Houston, TX 77030 USA. [Thomas, Eric J.] Univ Texas Houston, Mem Hermann Ctr Healthcare Qual & Safety, Div Gen Med, Univ Texas Med Sch Houston,Dept Med, Houston, TX USA. [Sittig, Dean F.] Univ Texas Sch Biomed Informat, Houston, TX USA. [Sittig, Dean F.] UT Mem Hermann Ctr Healthcare Qual & Safety, Houston, TX USA. RP Singh, H (reprint author), Baylor Coll Med, Houston VA Hlth Serv Res & Dev Ctr Excellence, Houston, TX 77030 USA. NR 2 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 0002-9343 J9 AM J MED JI Am. J. Med. PD OCT PY 2010 VL 123 IS 10 BP E21 EP E21 DI 10.1016/j.amjmed.2010.06.008 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 656WR UT WOS:000282372300014 ER PT J AU Almandoz, JED Schaefer, PW Goldstein, JN Rosand, J Lev, MH Gonzalez, RG Romero, JM AF Almandoz, J. E. Delgado Schaefer, P. W. Goldstein, J. N. Rosand, J. Lev, M. H. Gonzalez, R. G. Romero, J. M. TI Practical Scoring System for the Identification of Patients with Intracerebral Hemorrhage at Highest Risk of Harboring an Underlying Vascular Etiology: The Secondary Intracerebral Hemorrhage Score SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID ANGIOGRAPHY SPOT SIGN; PREDICTS HEMATOMA EXPANSION; CT ANGIOGRAPHY; ARTERIOVENOUS-MALFORMATIONS; CONTRAST EXTRAVASATION; INTRACRANIAL HEMORRHAGE; CEREBRAL-ANGIOGRAPHY; COMPUTED-TOMOGRAPHY; NATURAL-HISTORY; BRAIN AB BACKGROUND AND PURPOSE: An ICH patient's risk of harboring an underlying vascular etiology varies according to baseline clinical and NCCT characteristics. Our aim was to develop a practical scoring system to stratify patients with ICH according to their risk of harboring a vascular etiology. MATERIALS AND METHODS: Using a data base of 623 patients with ICH evaluated with MDCTA during a 9-year period, we developed a scoring system based on baseline clinical characteristics (age group [0-2 points], sex [0-1 point], neither known HTN nor impaired coagulation [0-1 point)), and NCCT categorization (0-2 points) to predict the risk of harboring a vascular lesion as the ICH etiology (SICH score). We subsequently applied the SICH score to a prospective cohort of 222 patients with ICH who presented to our emergency department during a 13-month period. Using ROC analysis, we calculated the AUC and MOP for the SICH score in both the retrospective and prospective patient cohorts separately and the entire patient population. Patients with SAH in the basal cisterns were excluded. RESULTS: A vascular etiology was found in 120 of 845 patients with ICH evaluated with MDCTA (14.2%), most commonly AVMs (45.8%), aneurysms with purely intraparenchymal rupture (21.7%), and DVSTs (16.7%). The MOP was reached at a SICH score of >2, with the highest incidence of vascular ICH etiologies in patients with SICH scores of 3(18.5%), 4(39%), 5 (84.2%), and 6(100%). There was no significant difference in the AUC between both patient cohorts (0.86-0.87). CONCLUSIONS: The SICH score successfully predicts a given ICH patient's risk of harboring an underlying vascular etiology and could be used as a guide to select patients with ICH for neurovascular evaluation to exclude the presence of a vascular abnormality. C1 [Almandoz, J. E. Delgado; Schaefer, P. W.; Lev, M. H.; Gonzalez, R. G.; Romero, J. M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Neuroradiol,Dept Radiol, Boston, MA USA. [Goldstein, J. N.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. [Rosand, J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Neurol, Boston, MA USA. [Rosand, J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA USA. [Almandoz, J. E. Delgado] Washington Univ, Mallinckrodt Inst Radiol, Div Neuroradiol, St Louis, MO 63110 USA. RP Almandoz, JED (reprint author), Washington Univ, Mallinckrodt Inst Radiol, Div Neuroradiol, Campus Box 8131,510 S Kingshighway Blvd, St Louis, MO 63110 USA. EM delgadoj@mir.wustl.edu RI Goldstein, Joshua/H-8953-2016 FU American Heart Association [0755984T]; National Institutes of Health/National Institute of Neurological Disorders and Stroke [K23NS059774] FX The following sources of funding were used, in part, for the preparation of this manuscript: American Heart Association Grant-in-Aid 0755984T and the National Institutes of Health/National Institute of Neurological Disorders and Stroke grant K23NS059774. NR 32 TC 16 Z9 16 U1 0 U2 1 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD OCT PY 2010 VL 31 IS 9 BP 1653 EP 1660 DI 10.3174/ajnr.A2156 PG 8 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 665BY UT WOS:000283011300021 ER PT J AU Payabvash, S Kamalian, S Fung, S Wang, Y Passanese, J Kamalian, S Souza, LCS Kemmling, A Harris, GJ Halpern, EF Gonzalez, RG Furie, KL Lev, MH AF Payabvash, S. Kamalian, S. Fung, S. Wang, Y. Passanese, J. Kamalian, S. Souza, L. C. S. Kemmling, A. Harris, G. J. Halpern, E. F. Gonzalez, R. G. Furie, K. L. Lev, M. H. TI Predicting Language Improvement in Acute Stroke Patients Presenting with Aphasia: A Multivariate Logistic Model Using Location-Weighted Atlas-Based Analysis of Admission CT Perfusion Scans SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID RECOVERY; PENUMBRA AB BACKGROUND AND PURPOSE: Prediction of functional outcome immediately after stroke onset can guide optimal management. Most prognostic grading scales to date, however, have been based on established global metrics such as total NIHSS score, admission infarct volume, or intracranial occlusion on CTA. Our purpose was to construct a more focused, location-weighted multivariate model for the prediction of early aphasia improvement, based not only on traditional clinical and imaging parameters, but also on atlas-based structure/function correlation specific to the clinical deficit, using CT perfusion imaging. MATERIALS AND METHODS: Fifty-eight consecutive patients with aphasia due to first-time ischemic stroke of the left hemisphere were included. Language function was assessed on the basis of the patients admission and discharge NIHSS scores and clinical records. All patients had brain CTP and CIA within 9 hours of symptom onset. For image analysis, all CTPs were automatically coregistered to MNI-152 brain space and parcellated into mirrored cortical and subcortical regions. Multiple logistic regression analysis was used to find independent imaging and clinical predictors of language recovery. RESULTS: By the time of discharge, 21 (36%) patients demonstrated improvement of language. Independent factors predicting improvement in language included rCBF of the angular gyrus GM (BA 3 9) and the lower third of the insular ribbon, proximal cerebral artery occlusion on admission CTA, and aphasia score on the admission NIHSS examination. Using these 4 variables, we developed a multivariate logistic regression model that could estimate the probability of early improvement in aphasia and predict functional outcome with 91% accuracy. CONCLUSIONS: An imaging-based location-weighted multivariate model was developed to predict early language improvement of patients with aphasia by using admission data collected within 9 hours of stroke onset. This pilot model should be validated in a larger, prospective study; however, the semiautomated atlas-based analysis of brain CTP, along with the statistical approach, could be generalized for prediction of other outcome measures in patients with stroke. C1 [Payabvash, S.; Kamalian, S.; Fung, S.; Passanese, J.; Kamalian, S.; Souza, L. C. S.; Harris, G. J.; Halpern, E. F.; Gonzalez, R. G.; Lev, M. H.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. [Halpern, E. F.] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [Furie, K. L.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Wang, Y.] Univ Western Ontario, Schulich Sch Med & Dent, London, ON, Canada. [Kemmling, A.] Univ Munster, Dept Radiol, Med Ctr, Munster, Germany. Harvard Univ, Sch Med, Boston, MA USA. RP Lev, MH (reprint author), Massachusetts Gen Hosp, Dept Radiol GRB285, POB 9657, Boston, MA 02114 USA. EM mlev@partners.org RI Kamalian, Shervin/D-7667-2013; OI Kamalian, Shervin/0000-0001-8962-4773; Kamalian, Shahmir/0000-0002-9640-8144; Fung, Steve/0000-0002-1177-682X FU National Institutes of Health [P50 NS051343]; Agency for Healthcare Research and Quality [AHRQ R01 HS11392]; Massachusetts General Hospital Clinical Research Center, Harvard Clinical and Translational Science Center, National Center for Research Resources [1 UL1 RR025758-01] FX This work was supported by the Specialized Programs of Translational Research in Acute Stroke Network grant funded by the National Institutes of Health (P50 NS051343), the Agency for Healthcare Research and Quality grant AHRQ R01 HS11392, and the Massachusetts General Hospital Clinical Research Center (1 UL1 RR025758-01) Harvard Clinical and Translational Science Center, from the National Center for Research Resources. NR 22 TC 19 Z9 20 U1 0 U2 5 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD OCT PY 2010 VL 31 IS 9 BP 1661 EP 1668 DI 10.3174/ajnr.A2125 PG 8 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 665BY UT WOS:000283011300022 PM 20488905 ER PT J AU Jackson, D Earnshaw, SR Farkouh, R Schwamm, L AF Jackson, D. Earnshaw, S. R. Farkouh, R. Schwamm, L. TI Cost-Effectiveness of CT Perfusion for Selecting Patients for Intravenous Thrombolysis: A US Hospital Perspective SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID ACUTE ISCHEMIC-STROKE; TISSUE-PLASMINOGEN ACTIVATOR; MRI; ASSOCIATION; EMERGENCY; ATLANTIS; THERAPY; TRIALS; ECASS; MODEL AB BACKGROUND AND PURPOSE: Improved selection of patients with stroke for IV tPA treatment may enhance clinical outcomes. Given the limited availability of MR imaging in hospitals, we examined the cost-effectiveness of adding CTP to the usual CT-based methods for selecting patients on the basis of the presence and extent of penumbra. MATERIALS AND METHODS: A decision-analytic model estimated the costs and outcomes associated with penumbra-based CTP selection in a patient population similar to that enrolled in the IV tPA clinical trials. Model inputs were obtained from published literature, clinical trial data, standard US costing sources, and expert opinion. Cost per life-year saved and cost per QALY gained were estimated from a hospital perspective. RESULTS: Addition of penumbra-based CTP to standard unenhanced CT improved favorable outcome (mRS, <= 1) by 0.59% and reduced cost by $42 compared with selection based on unenhanced CT alone. Life-years and QALYs improved. Multivariate sensitivity analysis predicted cost-effectiveness (<=$50,000 per QALY) in 89.2% of simulation runs. CONCLUSIONS: Using penumbra-based CTP after routine CT to select patients with ischemic stroke for IV tPA is cost-effective compared with the usual CT-based methods for hospitals. With the ease of access of CTP, penumbra-based selection methods may be readily available to hospitals. Thus, this economic analysis may lend further support to the consideration of a paradigm shift in acute stroke evaluation. C1 [Jackson, D.] GE Healthcare, Chalfont St Giles HP8 4SP, Bucks, England. [Earnshaw, S. R.; Farkouh, R.] Hlth Solut, Res Triangle Pk, NC USA. [Schwamm, L.] Harvard Univ, Sch Med, Dept Neurol, Massachusetts Gen Hosp, Boston, MA 02115 USA. RP Jackson, D (reprint author), GE Healthcare, Chalfont St Giles HP8 4SP, Bucks, England. EM daniel.jackson@ge.com OI Schwamm, Lee/0000-0003-0592-9145 FU GE Healthcare; GE Healthcare and pharmaceutical companies FX This work was funded by GE Healthcare.; Drs. Earnshaw and Farkouh are employees of RTI Health Solutions, an independent contract research organization that has received research funding for this and other studies from GE Healthcare and pharmaceutical companies that market medical devices, diagnostics, and drugs for use in the treatment of patients with stroke and other medical conditions. Mr. Jackson is an employee of GE Healthcare, a medical device and diagnostics manufacturer. Dr. Schwamm is Vice Chairman of the Department of Neurology at Massachusetts General Hospital and Associate Professor of Neurology at the Harvard Medical School. He is a paid consultant for RTI Health Solutions. He serves on the advisory board of Coaxia, a maker of medical devices for acute stroke treatment, and serves on the international steering committee for the DIAS3/4 trial, a trial of extended window thrombolysis using desmoteplase; he occasionally provides expert legal testimony in court cases involving acute stroke management. NR 29 TC 18 Z9 19 U1 0 U2 3 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD OCT PY 2010 VL 31 IS 9 BP 1669 EP 1674 DI 10.3174/ajnr.A2138 PG 6 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 665BY UT WOS:000283011300023 PM 20538823 ER PT J AU Witter, FR Zimmerman, AW Connors, SL AF Witter, Frank R. Zimmerman, Andrew W. Connors, Susan L. TI In utero beta 2 adrenergic agonist exposure and adverse neurophysiologic and behavioral outcomes REPLY SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Letter ID AUTISM C1 [Witter, Frank R.] Johns Hopkins Univ, Sch Med, Dept Gynecol & Obstet, Div Maternal Fetal Med, Baltimore, MD 21205 USA. [Zimmerman, Andrew W.] Johns Hopkins Univ, Dept Neurol & Dev Med,Sch Med, Dept Neurol,Dept Psychiat & Pediat, Kennedy Krieger Inst, Baltimore, MD 21205 USA. [Zimmerman, Andrew W.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Div Maternal Fetal Med, Baltimore, MD 21205 USA. [Connors, Susan L.] Harvard Univ, Sch Med, LADDERS Clin, Mass Gen Hosp, Boston, MA USA. RP Witter, FR (reprint author), Johns Hopkins Univ, Sch Med, Dept Gynecol & Obstet, Div Maternal Fetal Med, Baltimore, MD 21205 USA. EM fwitter@jhmi.edu NR 6 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD OCT PY 2010 VL 203 IS 4 BP E14 EP E15 DI 10.1016/j.ajog.2010.04.024 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 655WT UT WOS:000282287000008 ER PT J AU Kang, NL Yaqoob, U Geng, ZM Bloch, K Liu, CS Gomez, T Billadeau, D Shah, V AF Kang, Ningling Yaqoob, Usman Geng, Zhimin Bloch, Kenneth Liu, Chunsheng Gomez, Timothy Billadeau, Daniel Shah, Vijay TI Focal Adhesion Assembly in Myofibroblasts Fosters a Microenvironment that Promotes Tumor Growth SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID VASODILATOR-STIMULATED PHOSPHOPROTEIN; HEPATIC STELLATE CELLS; HUMAN BREAST-CANCER; ENA/VASP PROTEINS; ACTIN CYTOSKELETON; VASP; EXPRESSION; MOTILITY; MATRIX; METASTASIS AB Cells within the tumor microenvironment influence tumor growth through multiple mechanisms. Pericytes such as hepatic stellate cells are an important cell within the tumor microenvironment; their transformation into highly motile myofibroblasts leads to angiogenesis, stromal cell recruitment, matrix deposition, and ensuing tumor growth. Thus, a better understanding of mechanisms that regulate motility of pericytes is required. Focal adhesions (FM) form a physical link between the extracellular environment and the actin cytoskeleton, a requisite step for cell motility. FM contain a collection of proteins including the Ena/VASP family member, vasodilator-stimulated phosphoprotein (VASP); however, a role for VASP in FA development has been elusive. Using a comprehensive siRNA knockdown approach and a variety of VASP mutants coupled with complementary cell imaging methodologies, we demonstrate a requirement of VASP for optimal development of FM and cell spreading in LX2 liver myofibroblasts, which express high levels of endogenous VASP. Rac1, a binding partner of VASP, acts in tandem with VASP to regulate FM. In vivo, perturbation of Ena/VASP function in tumor myofibroblast precursor cells significantly reduces pericyte recruitment to tumor vasculature, myofibroblastic transformation, tumor angiogenesis, and tumor growth, providing in vivo pathobiologic relevance to these findings. Taken together, our results identify Ena/VASP as a significant modifier of tumor growth through regulation of FA dynamics and ensuing pericyte/myofibroblast function within the tumor microenvironment. (Am J Pathol 2010, 177:1888-1900; DOI: 10.2353/ajpath.2010.100187) C1 [Kang, Ningling; Yaqoob, Usman; Geng, Zhimin; Liu, Chunsheng; Shah, Vijay] Mayo Clin, GI Res Unit, Rochester, MN 55905 USA. [Kang, Ningling; Yaqoob, Usman; Geng, Zhimin; Liu, Chunsheng; Shah, Vijay] Mayo Clin, Canc Cell Biol Program, Rochester, MN 55905 USA. [Gomez, Timothy; Billadeau, Daniel] Mayo Clin, Dept Immunol, Rochester, MN 55905 USA. [Bloch, Kenneth] Massachusetts Gen Hosp, Anesthesia Ctr Crit Care Res, Boston, MA 02114 USA. RP Kang, NL (reprint author), Mayo Clin, GI Res Unit, 200 1st St SW, Rochester, MN 55905 USA. EM kang.ningling@mayo.edu; shah.vijay@mayo.edu FU NIDDK Center [K01 CA]; ALF/AASLD; [R01 DK] FX Supported through R01 DK (VS.), P30 NIDDK Center grant, K01 CA, and an ALF/AASLD 2006 Sheila Sherlock grant (N.K.). NR 55 TC 12 Z9 12 U1 0 U2 3 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD OCT PY 2010 VL 177 IS 4 BP 1888 EP 1900 DI 10.2353/ajpath.2010.100187 PG 13 WC Pathology SC Pathology GA 658NG UT WOS:000282496100032 PM 20802179 ER PT J AU Cowerd, RB Asmar, MM Alderman, JM Alderman, EA Garland, AL Busby, WH Bodnar, WM Rusyn, I Medoff, BD Tisch, R Mayer-Davis, E Swenbere, JA Zeisel, SH Combs, TP AF Cowerd, Rachael B. Asmar, Melissa M. Alderman, J. McKee Alderman, Elizabeth A. Garland, Alaina L. Busby, Walker H. Bodnar, Wanda M. Rusyn, Ivan Medoff, Benjamin D. Tisch, Roland Mayer-Davis, Elizabeth Swenbere, James A. Zeisel, Steven H. Combs, Terry P. TI Adiponectin Lowers Glucose Production by Increasing SOGA SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID ACTIVATED PROTEIN-KINASE; ADIPOSE-SPECIFIC PROTEIN; TYPE-2 DIABETIC-PATIENTS; ISOLATED RAT HEPATOCYTES; INSULIN SENSITIVITY; AUTOPHAGIC PROTEOLYSIS; PLASMA-CONCENTRATIONS; PHOSPHORYLATION; RECEPTOR; OBESITY AB Adiponectin is a hormone that lowers glucose production by increasing liver insulin sensitivity. Insulin blocks the generation of biochemical intermediates for glucose production by inhibiting autophagy. However, autophagy is stimulated by an essential mediator of adiponectin action, AMPK. This deadlock led to our hypothesis that adiponectin inhibits autophagy through a novel mediator. Mass spectrometry revealed a novel protein that we call suppressor of glucose by autophagy (SOGA) in adiponectin-treated hepatoma cells. Adiponectin increased SOGA in hepatocytes, and siRNA knockdown of SOGA blocked adiponectin inhibition of glucose production. Furthermore, knockdown of SOGA increased late autophagosome and lysosome staining and the secretion of valine, an amino acid that cannot be synthesized or metabolized by liver cells, suggesting that SOGA inhibits autophagy. SOGA decreased in response to AICAR, an activator of AMPK, and LY294002, an inhibitor of the insulin signaling intermediate, PI3K. AICAR reduction of SOGA was blocked by adiponectin; however, adiponectin did not increase SOGA during PI3K inhibition, suggesting that adiponectin increases SOGA through the insulin signaling pathway. SOGA contains an internal signal peptide that enables the secretion of a circulating fragment of SOGA, providing a surrogate marker for intracellular SOGA levels. Circulating SOGA increased in parallel with adiponectin and insulin activity in both humans and mice. These results suggest that adiponectin-mediated increases in SOGA contribute to the inhibition of glucose production. (Am J Pathol 2010, 177:1936-1945; DOI: 10.2353/ajpath.2010.100363) C1 [Cowerd, Rachael B.; Asmar, Melissa M.; Alderman, J. McKee; Alderman, Elizabeth A.; Mayer-Davis, Elizabeth; Zeisel, Steven H.; Combs, Terry P.] Univ N Carolina, Sch Med, Dept Nutr, Chapel Hill, NC 27599 USA. [Garland, Alaina L.; Tisch, Roland] Univ N Carolina, Sch Med, Dept Microbiol & Immunol, Chapel Hill, NC 27599 USA. [Busby, Walker H.] Univ N Carolina, Sch Med, Dept Med, Chapel Hill, NC 27599 USA. [Bodnar, Wanda M.; Rusyn, Ivan; Swenbere, James A.] Univ N Carolina, Sch Med, Dept Environm Sci & Engn, Chapel Hill, NC 27599 USA. Univ N Carolina, Gillings Sch Global Publ Hlth, Chapel Hill, NC 27599 USA. [Medoff, Benjamin D.] Massachusetts Gen Hosp, Pulm & Crit Care Unit, Boston, MA 02114 USA. RP Combs, TP (reprint author), Univ N Carolina, Sch Med, Dept Nutr, 135 Dauer Dr,Michael Hooker Res Bldg,Room 2002, Chapel Hill, NC 27599 USA. EM terrycombs@unc.edu RI Rusyn, Ivan/S-2426-2016 FU National Institutes of Diabetes and Digestive and Kidney Diseases [DK075573, DK056350]; Allergy and Infectious Diseases [AI066075]; Environmental Health Sciences [ES010126]; Graduate Women in Science Fellowship FX Supported by grants from the National Institutes of Diabetes and Digestive and Kidney Diseases (DK075573 and DK056350), Allergy and Infectious Diseases (AI066075), Environmental Health Sciences (ES010126) and a Graduate Women in Science Fellowship. The mRNA and predicted amino acid sequences for murine SOGA were submitted to GENBANK (FJ977045). NR 51 TC 6 Z9 8 U1 0 U2 4 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD OCT PY 2010 VL 177 IS 4 BP 1936 EP 1945 DI 10.2353/ajpath.2010.100363 PG 10 WC Pathology SC Pathology GA 658NG UT WOS:000282496100036 ER PT J AU Stuebe, A Ecker, J Bates, DW Zera, C Bentley-Lewis, R Seely, E AF Stuebe, Alison Ecker, Jeffrey Bates, David W. Zera, Chloe Bentley-Lewis, Rhonda Seely, Ellen TI Barriers to Follow-up for Women with a History of Gestational Diabetes SO AMERICAN JOURNAL OF PERINATOLOGY LA English DT Article DE Gestational diabetes; evidence-based practice; electronic medical record; type 2 diabetes ID IMPAIRED GLUCOSE-TOLERANCE; OBSTETRICIAN-GYNECOLOGISTS; RANDOMIZED-TRIAL; LIFE-STYLE; MELLITUS; PREVENTION; MANAGEMENT; OPPORTUNITIES; POPULATION; PHYSICIANS AB Women with gestational diabetes (GDM) are at increased risk for type 2 diabetes (T2DM), but many do not receive recommended follow-up. We sought to identify barriers to follow-up screening. We surveyed primary care providers (PCPs) and obstetric and gynecology care providers (OBCPs) in a large health system. We also assessed documentation of GDM history in the health care system's electronic medical record. Four hundred seventy-eight clinicians were surveyed, among whom 207 responded. Most participants (81.1%) gave an accurate estimate of risk of progression to T2DM. PCPs were less likely than OBCPs to ask patients about history of GDM (odds ratio [OR] 0.43, 95% confidence interval [CI] 0.20 to 0.90), but they were far more likely to indicate that they order glucose screening for women with a known history (OR 4.31, 95% CI 2.01 to 9.26). Providers identified poor communication between OBCPs and PCPs as a major barrier to screening. Fewer than half (45.8%) of 450 women with GDM by glucose tolerance test criteria had that history documented on their electronic problem list. Clinicians are aware that women with GDM are at high risk of developing type 2 diabetes, but they do not routinely assess and screen patients, and communication between OBCPs and PCPs can be improved. C1 [Stuebe, Alison] Univ N Carolina, Dept Obstet & Gynecol, Div Maternal Fetal Med, Chapel Hill, NC 27599 USA. [Ecker, Jeffrey] Massachusetts Gen Hosp, Div Maternal Fetal Med, Dept Obstet & Gynaecol, Boston, MA 02114 USA. [Bates, David W.] Harvard Univ, Sch Med, Div Gen Internal Med, Brigham & Womens Hosp, Cambridge, MA 02138 USA. [Bates, David W.] Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. [Zera, Chloe] Brigham & Womens Hosp, Div Maternal Fetal Med, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA. [Bentley-Lewis, Rhonda; Seely, Ellen] Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. RP Stuebe, A (reprint author), Univ N Carolina, Dept Obstet & Gynecol, Div Maternal Fetal Med, 3010 Old Clin Bldg,CB 7516, Chapel Hill, NC 27599 USA. EM astuebe@med.unc.edu FU Partners IS Research Council FX This study was supported by the Partners IS Research Council. NR 25 TC 19 Z9 19 U1 1 U2 2 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0735-1631 J9 AM J PERINAT JI Am. J. Perinatol. PD OCT PY 2010 VL 27 IS 9 BP 705 EP 710 DI 10.1055/s-0030-1253102 PG 6 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 658XR UT WOS:000282528500005 PM 20387186 ER PT J AU Feng, Y Zou, L Si, R Nagasaka, Y Chao, W AF Feng, Yan Zou, Lin Si, Rui Nagasaka, Yasuko Chao, Wei TI Bone marrow MyD88 signaling modulates neutrophil function and ischemic myocardial injury SO AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY LA English DT Article DE ischemia; reperfusion; MyD88; Toll-like receptor; inflammation ID TOLL-LIKE RECEPTOR-4; REPERFUSION INJURY; SERUM DEPRIVATION; INFARCT SIZE; TNF-ALPHA; CELLS; EXPRESSION; MICE; ACTIVATION; HEART AB Feng Y, Zou L, Si R, Nagasaka Y, Chao W. Bone marrow MyD88 signaling modulates neutrophil function and ischemic myocardial injury. Am J Physiol Cell Physiol 299: C760-C769, 2010. First published July 14, 2010; doi:10.1152/ajpcell.00155.2010.-Myeloid differentiation factor 88 (MyD88), an adaptor critical for innate immune function, plays a role in neutrophil recruitment and myocardial injury after transient ischemia. However, how MyD88 signaling modulates neutrophil function and myocardial injury remains unclear. In an in vivo model of neutrophil migration and a chimeric model of MyD88 deletion, we demonstrated that Gr-1-positive (Gr-1(+)) neutrophil migration was significantly decreased by 68% in MyD88-deficient (Myd88(-/-)) mice and by 33% in knockout -> wild-type (KO -> WT; donor -> recipient) chimeric mice, which lacked MyD88 in bone marrow cells but maintained normal MyD88 expression in the heart. This marked attenuation in neutrophil migration was associated with decreased peritoneal neutrophil CXCR2 expression and lower peritoneal KC, a neutrophil chemoattractant, in MyD88(-/-) mice. Moreover, in vitro, KC induces significantly more downregulation of CXCR2 expression in MyD88(-/-) than WT neutrophils. In an in vivo model of myocardial ischemia-reperfusion (I/R) injury, KO -> WT chimeric mice had significantly smaller infarct sizes compared with the WT -> WT mice. While there was a marked increase in proinflammatory cytokine/chemokine expression in the myocardium following I/R, there was no significant difference between WT -> WT and KO -> WT mice. In contrast, Gr-1(+) neutrophil recruitment in the myocardium was markedly attenuated in MyD88(-/-) mice. Deletion of Toll-interleukin-1 receptor (TIR)-domain-containing adaptor protein-inducing interferon-beta-mediated transcription factor (Trif), another innate immune adaptor, had no effect on the KC-mediated CXCR2 downregulation or on myocardial neutrophil recruitment after I/R. Taken together, these findings suggest that MyD88 signaling is essential for maintaining neutrophil migratory function and chemokine receptor expression. MyD88 signaling in bone marrow-derived circulating cells may play a specific and critical role in the development of myocardial I/R-induced injury. C1 [Feng, Yan; Zou, Lin; Si, Rui; Nagasaka, Yasuko; Chao, Wei] Harvard Univ, Dept Anesthesia & Crit Care, Anesthesia Ctr Crit Care Res, Sch Med,Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Chao, W (reprint author), Harvard Univ, Dept Anesthesia & Crit Care, Anesthesia Ctr Crit Care Res, Sch Med,Massachusetts Gen Hosp, GRJ 4-444,55 Fruit St, Boston, MA 02114 USA. EM wchao@partners.org RI Feng, Yan/H-5808-2012 FU National Institutes of Health [GM-080906]; American Heart Association [0755890T] FX This work was supported by National Institutes of Health Grant GM-080906 and American Heart Association Grant 0755890T. NR 40 TC 21 Z9 21 U1 0 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6143 J9 AM J PHYSIOL-CELL PH JI Am. J. Physiol.-Cell Physiol. PD OCT PY 2010 VL 299 IS 4 BP C760 EP C769 DI 10.1152/ajpcell.00155.2010 PG 10 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 653YE UT WOS:000282133500007 PM 20631245 ER PT J AU Sheth, RA Mahmood, U AF Sheth, Rahul A. Mahmood, Umar TI Optical molecular imaging and its emerging role in colorectal cancer SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Review DE cancer genetics; animal studies; endoscopy; fluorescence ID GROWTH-FACTOR RECEPTOR; IN-VIVO DIAGNOSIS; CONTRAST AGENTS; COLON-CANCER; TUMOR ANGIOGENESIS; INTEGRIN ALPHA(V)BETA(3); CONFOCAL ENDOMICROSCOPY; MONOCLONAL-ANTIBODY; TARGETED THERAPY; BLOOD CLEARANCE AB Colorectal cancer remains a major cause of morbidity and mortality in the United States. The advent of molecular therapies targeted against specific, stereotyped cellular mutations that occur in this disease has ushered in new hope for treatment options. However, key questions regarding optimal dosing schedules, dosing duration, and patient selection remain unanswered. In this review, we describe how recent advances in molecular imaging, specifically optical molecular imaging with fluorescent probes, offer potential solutions to these questions. We begin with an overview of optical molecular imaging, including discussions on the various methods of design for fluorescent probes and the clinically relevant imaging systems that have been built to image them. We then focus on the relevance of optical molecular imaging to colorectal cancer. We review the most recent data on how this imaging modality has been applied to the measurement of treatment efficacy for currently available as well as developmental molecularly targeted therapies. We then conclude with a discussion on how this imaging approach has already begun to be translated clinically for human use. C1 [Mahmood, Umar] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Nucl Med & Mol Imaging,Dept Radiol, Boston, MA 02114 USA. RP Mahmood, U (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Nucl Med & Mol Imaging,Dept Radiol, 55 Fruit St,White 427, Boston, MA 02114 USA. EM umahmood@mgh.harvard.edu FU NIBIB NIH HHS [R01 EB001872, R01 EB001872-05] NR 134 TC 11 Z9 11 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD OCT PY 2010 VL 299 IS 4 BP G807 EP G820 DI 10.1152/ajpgi.00195.2010 PG 14 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 655EF UT WOS:000282226200002 PM 20595618 ER PT J AU Deo, M Boyle, PM Kim, AM Vigmond, EJ AF Deo, Makarand Boyle, Patrick M. Kim, Albert M. Vigmond, Edward J. TI Arrhythmogenesis by single ectopic beats originating in the Purkinje system SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE computer modeling; bundle branch reentry; afterdepolarizations ID BUNDLE-BRANCH REENTRY; VENTRICULAR CONDUCTION SYSTEM; EARLY AFTERDEPOLARIZATIONS; TRIGGERED ACTIVITY; DISCONTINUOUS CONDUCTION; CARDIAC-ARRHYTHMIAS; ELECTRICAL-ACTIVITY; BIDOMAIN EQUATIONS; COMPUTER-MODEL; TACHYCARDIA AB Deo M, Boyle PM, Kim AM, Vigmond EJ. Arrhythmogenesis by single ectopic beats originating in the Purkinje system. Am J Physiol Heart Circ Physiol 299: H1002-H1011, 2010. First published July 9, 2010; doi:10.1152/ajpheart.01237.2009.-Cells in the Purkinje system (PS) are known to be more vulnerable than ventricular myocytes to secondary excitations during the action potential (AP) plateau or repolarization phases, known as early afterdepolarizations (EADs). Since myocytes have a lower intrinsic AP duration than the PS cells to which they are coupled, EADs occurring in distal branches of the PS are more likely to result in propagating ectopic beats. In this study, we use a computer model of the rabbit ventricles and PS to investigate the consequences of EADs occurring at different times and places in the cardiac conduction system. We quantify the role of tissue conductivity and excitability, as well as interaction with sinus excitation, in determining whether an EAD-induced ectopic beat will establish reentrant activity. We demonstrate how a single ectopic beat arising from an EAD in the distal PS can give rise to reentrant arrhythmia; in contrast, EADs in the proximal PS were unable to initiate reentry. Clinical studies have established the PS as a potential substrate for reentry, but the underlying mechanisms of these types of disorder are not well understood, nor are conditions leading to their development clearly defined; this work provides new insights into the role of the PS in such circumstances. Our findings indicate that simulated EADs in the distal PS can induce premature beats, which can lead to the tachycardias involving the conduction system due to interactions with sinus activity or impaired myocardial conduction velocity. C1 [Boyle, Patrick M.; Vigmond, Edward J.] Univ Calgary, Ctr BioEngn Res & Educ, Dept Elect & Comp Engn, Calgary, AB TZN 1N4, Canada. [Deo, Makarand] Univ Michigan, Ctr Arrhythmia Res, Ann Arbor, MI 48109 USA. [Kim, Albert M.] VA Boston Healthcare Syst, Cardiac Electrophysiol Sect, W Roxbury, MA USA. RP Vigmond, EJ (reprint author), Univ Calgary, Ctr BioEngn Res & Educ, Dept Elect & Comp Engn, 2500 Univ Dr NW, Calgary, AB TZN 1N4, Canada. EM vigmond@ucalgary.ca RI Vigmond, Edward/E-8988-2012 FU Natural Sciences and Engineering Research Council of Canada; Alberta Ingenuity Fund; Mathematics of Information Technology and Complex Systems NCE FX This research was supported by the Natural Sciences and Engineering Research Council of Canada, the Alberta Ingenuity Fund, and the Mathematics of Information Technology and Complex Systems NCE. NR 53 TC 20 Z9 21 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD OCT PY 2010 VL 299 IS 4 BP H1002 EP H1011 DI 10.1152/ajpheart.01237.2009 PG 10 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 675TF UT WOS:000283857300005 PM 20622103 ER PT J AU Hua, P Feng, WG Ji, SN Raij, L Jaimes, EA AF Hua, Ping Feng, Wenguang Ji, Shaonin Raij, Leopoldo Jaimes, Edgar A. TI Nicotine worsens the severity of nephropathy in diabetic mice: implications for the progression of kidney disease in smokers SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE reactive oxygen species; tobacco ID SMOOTH-MUSCLE-CELLS; STAGE RENAL-FAILURE; NADPH OXIDASE; NAD(P)H OXIDASE; ACETYLCHOLINE-RECEPTORS; ENDOTHELIAL-CELLS; CIGARETTE-SMOKING; ANGIOTENSIN-II; FIBRONECTIN EXPRESSION; ESSENTIAL-HYPERTENSION AB Hua P, Feng W, Ji S, Raij L, Jaimes EA. Nicotine worsens the severity of nephropathy in diabetic mice: implications for the progression of kidney disease in smokers. Am J Physiol Renal Physiol 299: F732-F739, 2010. First published August 4, 2010; doi:10.1152/ajprenal.00293.2010.-Epidemiological studies have established the role of cigarette smoking as a risk factor in the progression of chronic kidney disease, including diabetic nephropathy. We have previously reported that nicotine promotes mesangial cell proliferation and hypertrophy via activation of non-neuronal nicotinic acetylcholine receptors and that nicotine worsens renal injury in a model of acute glomerulonephritis (Jaimes E, Tian RX, Raij L. Am J Physiol Heart Circ Physiol 292: H76-H82, 2007; Jaimes EA, Tian RX, Joshi M, Raij L. Am J Nephrol 29: 319-326, 2009). These studies were designed to test the hypothesis that nicotine worsens renal injury in db/db mice, a well-established model of diabetic nephropathy, and that reactive oxygen species play an important as mediators of these effects. For these studies, nicotine (100 mu g/ml) was administered in the drinking water to control and db/db mice for 10 wk. Blood pressure was measured by the tail-cuff method, and urine was collected for proteinuria. At death, kidneys were collected for histology and molecular biology. The administration of nicotine did not result in significant changes in blood pressure or blood glucose and resulted in cotinine levels similar to those found in the plasma of smokers. In diabetic mice, the administration of nicotine significantly increased urinary protein excretion (1-fold), glomerular hypertrophy, and mesangial area (similar to 20%). These changes were accompanied by significant increases in NADPH oxidase 4 (similar to 30%) and increased nitrotyrosine and Akt expression. In vitro, we determined that nicotine has additive effects to high glucose on reactive oxygen species generation and Akt phosphorylation in human mesangial cells. These findings unveil novel mechanisms that may result in the development of novel strategies in the treatment and prevention of diabetic nephropathy in smokers. C1 [Hua, Ping; Feng, Wenguang; Ji, Shaonin; Jaimes, Edgar A.] Univ Alabama, Div Nephrol, Birmingham, AL USA. [Jaimes, Edgar A.] Birmingham Vet Affairs Med Ctr, Birmingham, AL USA. [Raij, Leopoldo] Univ Miami, Div Renal, Miami, FL USA. [Raij, Leopoldo] Miami Vet Affairs Med Ctr, Miami, FL USA. RP Jaimes, EA (reprint author), ZRB 637,1530 3rd Ave S, Birmingham, AL 35294 USA. EM ejaimes@uab.edu FU National Institutes of Health [ES014948]; Flight Attendants Research Institute; Florida Department of Health FX These studies were funded by National Institutes of Health Grant ES014948 (to E. A. Jaimes), a Clinical Investigator Award from the Flight Attendants Research Institute (to E. A. Jaimes), and a Team Science Project of the Florida Department of Health (to E. A. Jaimes and L. Raij.) NR 48 TC 29 Z9 29 U1 0 U2 7 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD OCT PY 2010 VL 299 IS 4 BP F732 EP F739 DI 10.1152/ajprenal.00293.2010 PG 8 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 658IP UT WOS:000282484000006 PM 20685820 ER PT J AU Huang, J Perlis, RH Lee, PH Rush, AJ Fava, M Sachs, GS Lieberman, J Hamilton, SP Sullivan, P Sklar, P Purcell, S Smoller, JW AF Huang, Jie Perlis, Roy H. Lee, Phil H. Rush, A. John Fava, Maurizio Sachs, Gary S. Lieberman, Jeffrey Hamilton, Steven P. Sullivan, Patrick Sklar, Pamela Purcell, Shaun Smoller, Jordan W. TI Cross-Disorder Genomewide Analysis of Schizophrenia, Bipolar Disorder, and Depression SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID 22Q11 DELETION SYNDROME; WIDE ASSOCIATION; II DISORDER; TRANSCRIPTION FACTOR; UNIPOLAR DEPRESSION; DAOA/G30 LOCUS; CELIAC-DISEASE; FAMILY; ADRENOMEDULLIN; METAANALYSIS AB Objective: Family and twin studies indicate substantial overlap of genetic influences on psychotic and mood disorders. Linkage and candidate gene studies have also suggested overlap across schizophrenia, bipolar disorder, and major depressive disorder. The purpose of this study was to apply genomewide association study (GWAS) analysis to address the specificity of genetic effects on these disorders. Method: The authors combined GWAS data from three large effectiveness studies of schizophrenia (CATIE, genotyped: N = 741), bipolar disorder (STEP-BD, genotyped: N = 1,575), and major depressive disorder (STAR*D, genotyped: N = 1,938) as well as from psychiatrically screened control subjects (NIMH-Genetics Repository: N = 1,204). A two-stage analytic procedure involving an omnibus test of allele frequency differences among case and control groups was applied, followed by a model selection step to identify the best-fitting model of allelic effects across disorders. Results: The strongest result was seen for a single nucleotide polymorphism near the adrenomedullin (ADM) gene (rs6484218), with the best-fitting model indicating that the effect was specific to bipolar II disorder. Findings also revealed evidence suggesting that several genes may have effects that transcend clinical diagnostic boundaries, including variants in NPAS3 that showed pleiotropic effects across schizophrenia, bipolar disorder, and major depressive disorder. Conclusions: This study provides the first genomewide significant evidence implicating variants near the ADM gene on chromosome 11p15 in psychopathology, with effects that appear to be specific to bipolar II disorder. Although genomewide significant evidence of cross-disorder effects was not detected, the results provide evidence that there are both pleiotropic and disorder-specific effects on major mental illness and illustrate an approach to dissecting the genetic basis of mood and psychotic disorders that can inform future largescale cross-disorder GWAS analyses. C1 [Smoller, Jordan W.] Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA. Massachusetts Gen Hosp, Psychiat Genet Program Mood & Anxiety Disorders, Dept Psychiat, Boston, MA 02114 USA. Broad Inst, Stanley Ctr Psychiat Res, Cambridge, MA USA. Duke Natl Univ Singapore, Grad Sch Med, Singapore, Singapore. Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY USA. New York State Psychiat Inst & Hosp, New York, NY 10032 USA. Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA. Univ N Carolina, Dept Genet, Chapel Hill, NC USA. Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA. Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. RP Smoller, JW (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Psychiat & Neurodev Genet Unit, Simches Res Bldg,185 Cambridge St, Boston, MA 02114 USA. EM jsmoller@hms.harvard.edu OI Hamilton, Steven/0000-0001-8106-6260; Rush, Augustus/0000-0003-2004-2382 FU AstraZeneca; Eli Lilly; Proteus Biomedical; Concordant Rater Systems; Brain Resource; University of Michigan; National Institute of Mental Health [N01MH-80001]; University of Texas Southwestern Medical Center; Abbott Laboratories; Alkermes; Aspect Medical Systems; BioResearch; BrainCells; Bristol-Myers Squibb; Cephalon; Clinical Trial Solutions; EnVivo Pharmaceuticals; Forest Pharmaceuticals; Ganeden; GlaxoSmithKline; J and J Pharmaceuticals; Lichtwer Pharma GmbH; Lorex Phramaceuticals; National Institute on Drug and Alcohol Abuse; Novartis; Organon; PamLab; Pfizer; Pharmavite; Roche; Sanofi-Aventis; Shire; Solvay Pharmaceuticals; Synthelabo; Wyeth-Ayerst; National Institutes of Health [MH-079799]; NIMH [N01 MH-90003, N01 MH-90001]; [N01-MH-80001] FX Dr. Perlis has received consulting fees from AstraZeneca, Eli Lilly, and Proteus Biomedical; and he has received royalties/patents from Concordant Rater Systems. Dr. Rush has received speaker's fees from Otsuka Pharmaceuticals; he has received consulting fees from Brain Resource and the University of Michigan; he has received research support from the National Institute of Mental Health; and he has received royalties from the University of Texas Southwestern Medical Center. Dr. Fava has received research support from Abbott Laboratories, Alkermes, Aspect Medical Systems, AstraZeneca, BioResearch, BrainCells, Bristol-Myers Squibb, Cephalon, Clinical Trial Solutions, Eli Lilly, EnVivo Pharmaceuticals, Forest Pharmaceuticals, Ganeden, GlaxoSmithKline, J and J Pharmaceuticals, Lichtwer Pharma GmbH, Lorex Phramaceuticals, NARSAD, National Center for Complementary and Alternative Medicine, National Institute on Drug and Alcohol Abuse, National Institute of Mental Health, Novartis, Organon, PamLab, Pfizer, Pharmavite, Roche, Sanofi-Aventis, Shire, Solvay Pharmaceuticals, Synthelabo, and Wyeth-Ayerst; he has served as an advisor and/or consultant to Abbott Laboratories, Affectis Pharmaceuticals AG, Amarin, Aspect Medical Systems, AstraZeneca, Auspex Pharmaceuticals, Bayer AG, Best Practice Project Management, BioMarin Pharmaceuticals, Biovail Pharmaceuticals, BrainCells, Bristol-Myers Squibb, Cephalon, Clinical Trials Solutions, CNS Response, Compellis, Cypress Pharmaceuticals, Dov Pharmaceuticals, Eisai, Eli Lilly, EPIX Pharmaceuticals, Euthymics Bioscience, Fabre-Kramer Pharmaceuticals, Forest Pharmaceuticals, GlaxoSmithKline, Grunenthal GmbH, Janssen Pharmaceutica, Jazz Pharmaceuticals, J and J Pharmaceuticals, Knoll Pharmaceuticals, Labopharm, Lorex Pharmaceuticals, Lundbeck, MedAvante, Merck, Methylation Sciences, Neuronetics, Novartis, Nutrition 21, Organon, PamLab, Pfizer, PharmaStar, Pharmavite, Precision Human Biolaboratory, Prexa Pharmaceuticals, PsychoGenics, Psylin Neurosciences, Ridge Diagnostics, Roche, Sanofi-Aventis, Sepracor, Schering-Plough, Solvay Pharmaceuticals, Somaxon, Somerset Pharmaceuticals, Synthelabo, Takeda, Tetragenex, TransForm Pharmaceuticals, Transcept Pharmaceuticals, Vanda Pharmaceuticals, and Wyeth-Ayerst Laboratories; he has received speaking and publishing fees from Adamed, Advanced Meeting Partners, American Psychiatric Association, American Society of Clinical Psychopharmacology, AstraZeneca, Belvoir, Boehringer-Ingelheim, Bristol-Myers Squibb, Cephalon, Eli Lilly, Forest Pharmaceuticals, GlaxoSmithKline, Imedex, Novartis, Organon, Pfizer, PharmaStar, Massachusetts General Hospital Psychiatry Academy/Primedia, Massachusetts General Hospital Psychiatry Academy/Reed-Elsevier, UBC, and Wyeth-Ayerst Laboratories; he is a shareholder with Compellis; he has received a patent for sequential parallel comparison of design (SPCD) and a patent application for a combination of azapirones and bupropion in the treatment of major depressive disorder; and he has received royalties for the Massachusetts General Hospital Cognitive and Physical Functioning Questionnaire, Massachusetts General Hospital SFI, Massachusetts General Hospital Antidepressant Treatment Response Questionnaire, Massachusetts General Hospital Discontinuation-Emergent Signs and Symptoms scale, and Massachusetts General Hospital SAFER. Dr.; Sachs has received research support from, served in a consulting or advisory capacity to, or participated in CME activities with Abbott Laboratories, AstraZeneca, Bristol-Myers Squibb, Cephalon, Concordant Rater Sysems, Eli Lilly, GlaxoSmithKline, Janssen, Memory Pharmaceuticals, Merck, the National Institute of Mental Health, Novartis, Schering-Plough, Otsuka, Pfizer, Repligen, Sanofi-Aventis, Sepacor, Shire, Solvay, and Wyeth; and he is a shareholder with Concordant Rater Systems. Dr. Lieberman has received grant/research support from Allon, AstraZeneca, BristolMyers Squibb, Forest Laboratories, GlaxoSmithKline, Janssen, Merck, and Pfizer; he has served as a consultant to Cephalon, Eli Lilly, and Pfizer; he has served on the advisory boards of AstraZeneca, Bioline, Eli Lilly, Forest Laboratories, GlaxoSmithKline, Janssen, Intracellular Therapies, Otsuka, Pfizer, Psychogenics, and Wyeth; he has a patent with Repligen; and he has participated in Data and Safety Monitoring Board activities with Solvay. Dr. Sullivan has received unrestricted research support from Eli Lilly and Expression Analysis (SAB). Dr. Smoller has served as a consultant to Herman Dana Trust and RTI International. Drs. Huang, Lee, Hamilton, Sklar, and Purcell report no financial relationships with commercial interests.; Supported by the National Institutes of Health grant MH-079799 (Dr. Smoller).; The authors thank Rutgers Cell and DNA Repository for extracting DNA and providing samples. The STEP-BD project was funded in whole or in part with Federal funds from the National Institute of Mental Health (NIMH), National Institutes of Health, under contract N01MH-80001 to Gary S. Sachs, M.D. (principal investigator), Michael E. Thase, M.D. (co-principal investigator), and Mark S. Bauer, M.D. (co-principal investigator). Active STEP-BD sites and principal investigators included: Baylor College of Medicine (Lauren B. Marangell, M.D.); Case University (Joseph R. Calabrese, M.D.); Massachusetts General Hospital and Harvard Medical School (Andrew A. Nierenberg, M.D.); Portland VA Medical Center (Peter Hauser, M.D.); Stanford University School of Medicine (Terence A. Ketter, M.D.); University of Colorado Health Sciences Center (Marshall Thomas, M.D.); University of Massachusetts Medical Center (Jayendra Patel, M.D.); University of Oklahoma College of Medicine (Mark D. Fossey, M.D.); University of Pennsylvania Medical Center (Laszlo Gyulai, M.D.); University of Pittsburgh Western Psychiatric Institute and Clinic (Michael E. Thase, M.D.); and University of Texas Health Science Center at San Antonio (Charles L. Bowden, M. D.). Collection of DNA from consenting participants in STEP-BD was supported by N01-MH-80001 (Gary S. Sachs, M. D., principal investigator). The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study was supported by federal funds from NIMH under contract N01 MH-90003 to the University of Texas Southwestern Medical Center at Dallas (A. John Rush, M. D., principal investigator). Genotyping of STAR*D samples was funded by NIMH (R01 MH-072802; Steven P. Hamilton, M. D., Ph.D., principal investigator). The CATIE project was funded by NIMH contract N01 MH-90001. Control subjects from the NIMH Schizophrenia Genetics Initiative (NIMH-GI) data and biomaterials were gathered by the Molecular Genetics of Schizophrenia II (MGS-2) collaboration. The investigators and co-investigators are: Evanston Northwestern Healthcare/Northwestern University, Evanston, Ill., MH-059571, Pablo V. Gejman, M. D. (collaboration coordinator; principal investigator), Alan R. Sanders, M.D.; Emory University School of Medicine, Atlanta, MH-59587, Farooq Amin, M.D. (principal investigator); Louisiana State University Health Sciences Center, New Orleans, MH-067257, Nancy Buccola A.P.R.N., B.C., M.S.N. (principal investigator); University of California-Irvine, Irvine, Calif., MH-60870, William Byerley, M. D. (principal investigator); Washington University, St. Louis, Mo., U01 MH-060879, C. Robert Cloninger, M. D. (principal investigator); University of Iowa, Iowa City, IA, MH-59566, Raymond Crowe, M.D. (principal investigator), Donald Black, M.D.; University of Colorado, Denver, Colo., MH-059565, Robert Freedman, M. D. (principal investigator); University of Pennsylvania, Philadelphia, MH-061675, Douglas Levinson, M.D. (principal investigator); University of Queensland, Queensland, Australia, MH-059588, Bryan Mowry, M.D. (principal investigator); Mt. Sinai School of Medicine, New York, MH-59586, Jeremy Silverman, Ph.D. (principal investigator). NR 57 TC 109 Z9 111 U1 2 U2 16 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD OCT PY 2010 VL 167 IS 10 BP 1254 EP 1263 DI 10.1176/appi.ajp.2010.09091335 PG 10 WC Psychiatry SC Psychiatry GA 656XP UT WOS:000282374700019 PM 20713499 ER PT J AU Soneji, S Lyer, SS Armstrong, K Asch, DA AF Soneji, Samir Lyer, Shally Shalini Armstrong, Katrina Asch, David A. TI Racial Disparities in Stage-Specific Colorectal Cancer Mortality: 1960-2005 SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID UNITED-STATES; COLON-CANCER; WHITES; SURVIVAL; BLACKS; HEALTH; CARE; RACE; CONSEQUENCES; CARCINOMA AB Objectives. We examined whether racial disparities in stage-specific colorectal cancer survival changed between 1960 and 2005. Methods. We used US Mortality Multiple-Cause-of-Death Data Files and intercensal estimates to calculate standardized mortality rates by gender and race from 1960 to 2005. We used Surveillance, Epidemiology, and End Results (SEER) data to estimate stage-specific colorectal cancer survival. To account for SEER sampling uncertainty, we used a bootstrap resampling procedure and fit a Cox proportional hazards model. Results. Between 1960-2005, patterns of decline in mortality rate as a result of colorectal cancer differed greatly by gender and race: 54% reduction for White women, 14% reduction for Black women, 39% reduction for White men, and 28% increase for Black men. Blacks consistently experienced worse rates of stage-specific survival and life expectancy than did Whites for both genders, across all age groups, and for localized, regional, and distant stages of the disease. Conclusions. The rates of stage-specific colorectal cancer survival differed among Blacks when compared with Whites during the 4-decade study period. Differences in stage-specific life expectancy were the result of differences in access to care or quality of care. More attention should be given to racial disparities in colorectal cancer management. (Am J Public Health. 2010;100: 1912-1916. doi:10.2105/AJPH.2009.184192) C1 [Soneji, Samir; Asch, David A.] Univ Penn, Robert Wood Johnson Hlth & Soc Scholars Program, Philadelphia, PA 19104 USA. [Lyer, Shally Shalini] Univ Penn, Grad Program Publ Hlth Studies, Div Gen Internal Med, Philadelphia, PA 19104 USA. [Armstrong, Katrina; Asch, David A.] Univ Penn, Leonard Davis Inst Hlth Econ, Div Gen Internal Med, Philadelphia, PA 19104 USA. [Asch, David A.] Philadelphia VA Med Ctr, Ctr Hlth Equ Res & Promot, Philadelphia, PA USA. RP Soneji, S (reprint author), Univ Penn, Robert Wood Johnson Hlth & Soc Scholars Program, 3641 Locust Walk, Philadelphia, PA 19104 USA. EM soneji@wharton.upenn.edu OI Asch, David/0000-0002-7970-286X FU Robert Wood Johnson Foundation FX We thank the Robert Wood Johnson Foundation Health & Society Scholars and Robert Wood Johnson Clinical Scholars programs for their financial support. NR 34 TC 47 Z9 47 U1 1 U2 2 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD OCT PY 2010 VL 100 IS 10 BP 1912 EP 1916 DI 10.2105/AJPH.2009.184192 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 656SC UT WOS:000282355900022 PM 20724684 ER PT J AU Mehta, KM Fung, KZ Kistler, CE Chang, A Walter, LC AF Mehta, Kala M. Fung, Kathy Z. Kistler, Christine E. Chang, Anna Walter, Louise C. TI Impact of Cognitive Impairment on Screening Mammography Use in Older US Women SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID ALZHEIMERS-DISEASE; HEALTH-STATUS; SURVIVAL; DEMENTIA; PREVALENCE; PREDICTORS; DIAGNOSIS; MORTALITY; PEOPLE AB Objectives. We evaluated mammography rates for cognitively impaired women in the context of their life expectancies, given that guidelines do not recommend screening mammography in women with limited life expectancies because harms outweigh benefits. Methods. We evaluated Medicare claims for women aged 70 years or older from the 2002 wave of the Health and Retirement Study to determine which women had screening mammography. We calculated population-based estimates of 2-year screening mammography prevalence and 4-year survival by cognitive status and age. Results. Women with severe cognitive impairment had lower rates of mammography (18%) compared with women with normal cognition (45%). Nationally, an estimated 120000 screening mammograms were performed among women with severe cognitive impairment despite this group's median survival of 3.3 years (95% confidence interval=2.8, 3.7). Cognitively impaired women who had high net worth and were married had screening rates approaching 50%. Conclusions. Although severe cognitive impairment is associated with lower screening mammography rates, certain subgroups with cognitive impairment are often screened despite lack of probable benefit. Given the limited life expectancy of women with severe cognitive impairment, guidelines should explicitly recommend against screening these women. (Am J Public Health. 2010;100:1917-1923. doi:10.2105/AJPH.2008.158485) C1 [Mehta, Kala M.; Kistler, Christine E.; Chang, Anna; Walter, Louise C.] Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94121 USA. [Fung, Kathy Z.] San Francisco VA Med Ctr, San Francisco, CA USA. RP Mehta, KM (reprint author), Univ Calif San Francisco, Div Geriatr, 4150 Clement St,Box 181G, San Francisco, CA 94121 USA. EM kala.mehta@ucsf.edu FU National Institute on Aging [NIA-K-01AG025444-01A1, NIA U01AG009740]; Department of Veterans Affairs Merit Review grant [IIR 04-427]; Robert Wood Johnson Physician Faculty Scholar; University of Michigan FX K M. Mehta is currently supported by a Research Career Scientist Award from the National Institute on Aging (NIA-K-01AG025444-01A1). She is currently an affiliate of the Center for Aging in Diverse Communities at University of California, San Francisco, a part of the P30 AG 15272 350 Resource Centers for Minority Aging Research Program (NIA, National Institute of Nursing Research, and the National Center for Minority Health and Health Disparities). L.C. Walter was supported by a Department of Veterans Affairs Merit Review grant (IIR 04-427) and is a Robert Wood Johnson Physician Faculty Scholar. The Health and Retirement Study is sponsored by the MA (grant NIA U01AG009740) and is conducted by the University of Michigan. NR 37 TC 20 Z9 21 U1 1 U2 3 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD OCT PY 2010 VL 100 IS 10 BP 1917 EP 1923 DI 10.2105/AJPH.2008.158485 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 656SC UT WOS:000282355900023 PM 20075325 ER PT J AU Conron, KJ Mimiaga, MJ Landers, SJ AF Conron, Kerith J. Mimiaga, Matthew J. Landers, Stewart J. TI A Population-Based Study of Sexual Orientation Identity and Gender Differences in Adult Health SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID BISEXUAL ADULTS; MENTAL-HEALTH; UNITED-STATES; GAY; DISORDERS; ACCESS; CARE; INDIVIDUALS; DISPARITIES; PREVALENCE AB Objectives. We provide estimates of several leading US adult health indicators by sexual orientation identity and gender to fill gaps in the current literature. Methods. We aggregated data from the 2001-2008 Massachusetts Behavioral Risk Factor Surveillance surveys (N=67359) to examine patterns in self-reported health by sexual orientation identity and gender, using multivariable logistic regression. Results. Compared with heterosexuals, sexual minorities (i.e., gays/lesbians, 2% of sample; bisexuals, 1%) were more likely to report activity limitation, tension or worry, smoking, drug use, asthma, lifetime sexual victimization, and HIV testing, but did not differ on 3-year Papanicolaou tests, lifetime mammography, diabetes, or heart disease. Compared with heterosexuals, bisexuals reported more barriers to health care, current sadness, past-year suicidal ideation, and cardiovascular disease risk. Gay men were less likely to be overweight or obese and to obtain prostate-specific antigen tests, and lesbians were more likely to be obese and to report multiple risks for cardiovascular disease. Binge drinking and lifetime physical intimate partner victimization were more common among bisexual women. Conclusions. Sexual orientation disparities in chronic disease risk, victimization, health care access, mental health, and smoking merit increased attention. More research on heterogeneity in health and health determinants among sexual minorities is needed. (Am J Public Health. 2010;100:1953-1960. doi:10.2105/AJPH.2009.174169) C1 [Conron, Kerith J.] Northeastern Univ, Inst Urban Hlth Res, Boston, MA 02115 USA. [Conron, Kerith J.] Harvard Univ, Harvard Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA 02115 USA. [Mimiaga, Matthew J.] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. [Mimiaga, Matthew J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Mimiaga, Matthew J.] Fenway Community Hlth Ctr, Ctr Populat Res LGRT Hlth, Fenway Inst, Boston, MA USA. [Landers, Stewart J.] John Snow Inc, Boston, MA USA. RP Conron, KJ (reprint author), Northeastern Univ, Inst Urban Hlth Res, 336 Int Village, Boston, MA 02115 USA. EM kconron@post.harvard.edu FU Massachusetts Department of Public Health HIV/AIDS Bureau; University of California at Los Angeles, through the Ford Foundation FX Funding for data analysis and article development was provided by the Massachusetts Department of Public Health HIV/AIDS Bureau and the Williams Project at the University of California at Los Angeles, through a grant from the Ford Foundation. NR 35 TC 208 Z9 211 U1 6 U2 37 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD OCT PY 2010 VL 100 IS 10 BP 1953 EP 1960 DI 10.2105/AJPH.2009.174169 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 656SC UT WOS:000282355900028 PM 20516373 ER PT J AU Chan, ED Bai, XY Kartalija, M Ormes, IM Ordways, DJ AF Chan, Edward D. Bai, Xiyuan Kartalija, Marinka Ormes, Ian M. Ordways, Diane J. TI Host Immune Response to Rapidly Growing Mycobacteria, an Emerging Cause of Chronic Lung Disease SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Review DE Mycobacterium abscessus; immune responses; rapidly growing mycobacteria; host defense ID TUMOR-NECROSIS-FACTOR; MACROPHAGE TNF-ALPHA; GROWTH-FACTOR-BETA; NONTUBERCULOUS MYCOBACTERIA; PULMONARY-DISEASE; AVIUM COMPLEX; INTERFERON-GAMMA; TGF-BETA; TUBERCULOSIS INFECTION; ABSCESSUS INFECTION AB Rapidly growing mycobacteria (RGM) are environmental organisms classified under the broader category of nontuberculous mycobacteria. The most common RGM to cause human diseases are Mycobacterium abscessus, Mycobacterium chelonae, Mycobacterium fortuitum, and Mycobacterium massiliense. Infections due to the RGM are an emerging health problem in the United States. Chronic pulmonary disease and skin/soft-tissue infections are the two most common disorders due to these organisms. Clinical outcomes in the treatment of M. abscessus infections are generally disappointing. Because less is known about the nature of the immune response to M. abscessus than for tuberculosis, we herein highlight the major clinical features associated with infections due to M. abscessus and other RGM, and review the known host immune response to RGM, drawing from experimental animal and clinical studies. Based on in vitro and in vivo murine models, Toll-like receptor 2, dectin-1, tumor necrosis factor (TNF)-alpha, IFN-gamma, leptin, T cells, and possibly neutrophils are important components in the host defense against RGM infections. However, excessive induction of TNF-alpha by the R morphotype of M. abscessus may allow it to be more pathogenic than the S morphotype. Clinical observations and/or genetic studies in humans corroborate many of the findings in animals in that those with cell-mediated immunodeficiency, genetic defects in IFN-gamma-IL-12 axis, and those individuals on TNF-alpha blockers are at increased risk for nontuberculous mycobacteria infections, including the RGM. However, much remains to be discovered on why seemingly healthy individuals, particularly slender postmenopausal women with thoracic cage anomalies, appear to be at increased risk. C1 [Chan, Edward D.; Bai, Xiyuan] Natl Jewish Hlth, Div Mycobacterial & Resp Infect, Denver, CO 80206 USA. [Chan, Edward D.] Denver Vet Affairs Med Ctr, Denver, CO USA. [Chan, Edward D.; Bai, Xiyuan] Univ Colorado Denver, Div Pulm Sci & Crit Care Med, Denver, CO USA. [Kartalija, Marinka] Univ Colorado Denver, Div Infect Dis, Denver, CO USA. [Ormes, Ian M.; Ordways, Diane J.] Colorado State Univ, Dept Microbiol Immunol & Pathol, Ft Collins, CO 80523 USA. RP Chan, ED (reprint author), Natl Jewish Hlth, Div Mycobacterial & Resp Infect, D509,Neustadt Bldg,1400 Jackson St, Denver, CO 80206 USA. EM chane@njhealth.org FU Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development FX This work was supported by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development (E.D.C.). NR 73 TC 33 Z9 33 U1 0 U2 2 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD OCT PY 2010 VL 43 IS 4 BP 387 EP 393 DI 10.1165/rcmb.2009-0276TR PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 660UY UT WOS:000282673100001 PM 20081053 ER PT J AU Alkadhi, H Leschka, S Trindade, PT Feuchtner, G Stolzmann, P Plass, A Baumueller, S AF Alkadhi, Hatem Leschka, Sebastian Trindade, Pedro T. Feuchtner, Gudrun Stolzmann, Paul Plass, Andre Baumueller, Stephan TI Cardiac CT for the Differentiation of Bicuspid and Tricuspid Aortic Valves: Comparison With Echocardiography and Surgery SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE bicuspid aortic valve; CT; echocardiography ID TOMOGRAPHY CORONARY-ANGIOGRAPHY; SPIRAL COMPUTED-TOMOGRAPHY; INFECTIVE ENDOCARDITIS; VENTRICULAR FUNCTION; HEART-DISEASE; REGURGITATION; PLANIMETRY; STENOSIS; RECOMMENDATIONS; FEASIBILITY AB OBJECTIVE. The purpose of this study is to evaluate the diagnostic performance of CT, compared with that of echocardiography and surgery, for differentiating between bicuspid and tricuspid aortic valves. MATERIALS AND Met hods. Forty-seven patients with bicuspid valve and 47 patients with tricuspid aortic valve underwent retrospectively ECG-gated dual-source CT and echocardiography. Thirty-four (72%) of the 47 patients with bicuspid aortic valve underwent valve surgery. Two independent blinded observers assessed the CT image quality of the aortic valve during diastole and systole on a 4-point scale, determined which phase allowed the differentiation of valve type, distinguished between tricuspid and bicuspid aortic valves, and assessed for the presence of a raphe. Diagnostic performance of CT was determined using echocardiography and surgery as the reference standard. RESULTS. According to echocardiography and surgery, seven (15%) of the 47 bicuspid aortic valves had no raphe, and 40 (85%) had a raphe. CT image quality was diagnostic (i.e., scores of 1-3) in all 94 patients in both diastole and systole. Among patients with bicuspid aortic valve and no raphe, differentiation between tricuspid and bicuspid aortic valves could be performed in diastole in 100% (7/7) of cases. Among patients with bicuspid aortic valve and raphe, differentiation was possible only in systole in 5% (2/40) of cases and when combining diastole and systole in 95% (38/40) of cases. In three bicuspid aortic valves with raphe, the valve was misclassified by CT as tricuspid aortic valve. Overall sensitivity and specificity of CT for the diagnosis of bicuspid aortic valve were 94% and 100%. CONCLUSION. CT is highly accurate for differentiation between bicuspid and tricuspid aortic valves. For bicuspid aortic valves without raphe, diastolic reconstructions are sufficient, whereas in those with a raphe, additional reconstructions in systole are required. C1 [Alkadhi, Hatem; Leschka, Sebastian; Feuchtner, Gudrun; Stolzmann, Paul; Baumueller, Stephan] Univ Zurich Hosp, Inst Diagnost Radiol, CH-8091 Zurich, Switzerland. [Alkadhi, Hatem] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA. [Trindade, Pedro T.] Univ Zurich Hosp, Ctr Cardiovasc, CH-8091 Zurich, Switzerland. [Plass, Andre] Univ Zurich Hosp, Cardiovasc Surg Clin, CH-8091 Zurich, Switzerland. RP Alkadhi, H (reprint author), Univ Zurich Hosp, Inst Diagnost Radiol, CH-8091 Zurich, Switzerland. EM halkadhi@partners.org NR 34 TC 21 Z9 21 U1 0 U2 0 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD OCT PY 2010 VL 195 IS 4 BP 900 EP 908 DI 10.2214/AJR.09.3813 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 652TU UT WOS:000282033600016 PM 20858816 ER PT J AU Shinagare, AB Jagannathan, JP Ramaiya, NH Hall, MN Van den Abbeele, AD AF Shinagare, Atul B. Jagannathan, Jyothi P. Ramaiya, Nikhil H. Hall, Matthew N. Van den Abbeele, Annick D. TI Adult Extragonadal Germ Cell Tumors SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE adult; extragonadal germ cell tumor; primary; metastases ID POSITRON-EMISSION-TOMOGRAPHY; MEDIASTINUM; RETROPERITONEUM; CHORIOCARCINOMA; CHEMOTHERAPY; CANCER; CT AB OBJECTIVE. The purpose of this article is to describe the key imaging features of primary and metastatic extragonadal germ cell tumors in adults. CONCLUSION. Extragonadal germ cell tumors primarily affect men during the third and fourth decades of life. Their imaging characteristics are nonspecific, and extragonadal germ cell tumors should always be included in the differential diagnosis of a midline anterior mediastinal or retroperitoneal mass. Levels of human chorionic gonadotropin or alpha-fetoprotein or both may be elevated, depending on the histologic subtype. C1 [Shinagare, Atul B.; Jagannathan, Jyothi P.; Ramaiya, Nikhil H.; Hall, Matthew N.; Van den Abbeele, Annick D.] Dana Farber Canc Inst, Dept Imaging, Boston, MA 02115 USA. [Shinagare, Atul B.; Jagannathan, Jyothi P.; Ramaiya, Nikhil H.; Hall, Matthew N.; Van den Abbeele, Annick D.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA. RP Shinagare, AB (reprint author), Dana Farber Canc Inst, Dept Imaging, 44 Binney St, Boston, MA 02115 USA. EM ashinagare@partners.org NR 21 TC 8 Z9 9 U1 0 U2 2 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD OCT PY 2010 VL 195 IS 4 BP W274 EP W280 DI 10.2214/AJR.09.4103 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 652TU UT WOS:000282033600042 PM 20858789 ER PT J AU Klos, CL Shellito, PC Rattner, DW Hodin, RA Cusack, JC Bordeianou, L Sylla, P Hong, TS Blaszkowsky, L Ryan, DP Lauwers, GY Chang, YC Berger, DL AF Klos, Coen L. Shellito, Paul C. Rattner, David W. Hodin, Richard A. Cusack, James C. Bordeianou, Liliana Sylla, Patricia Hong, Theodore S. Blaszkowsky, Lawrence Ryan, Davis P. Lauwers, Gregory Y. Chang, Yuchiao Berger, David L. TI The effect of neoadjuvant chemoradiation therapy on the prognostic value of lymph nodes after rectal cancer surgery SO AMERICAN JOURNAL OF SURGERY LA English DT Article DE Lymph nodes; Neoadjuvant therapy; Total mesorectal excision; Rectal cancer ID MESORECTAL EXCISION; COLORECTAL-CANCER; PREOPERATIVE RADIOTHERAPY; NUMBER; CHEMORADIOTHERAPY; IMPACT; SURVIVAL AB BACKGROUND: Neoadjuvant therapy may affect the prognostic impact of total lymph node harvests and lymph node positivity after surgery for rectal cancer. METHODS: We performed a retrospective review of 390 consecutive patients with histologically confirmed rectal cancer. Postoperative follow-up evaluation and survival were confirmed via medical record review. The impacts of lymph node positivity and total lymph node harvest on survival and recurrence are reflected as proportional hazard ratios (HRs). RESULTS: A total of 221 patients underwent neoadjuvant therapy, of whom 75 had positive nodes. Node-positive patients showed a significantly shorter survival time (HR, 2.89; P = .002) and time to local recurrence (HR, 6.36; P = .031) compared with patients without positive nodes. Survival and recurrence were not significantly different between patients with a total harvest of fewer than 12 nodes and patients with a higher lymph node harvest. CONCLUSIONS: After neoadjuvant treatment and total mesorectal excision, lymph node positivity is associated with significantly shorter survival and time to local recurrence in rectal cancer patients, whereas absolute total lymph node harvests likely have little impact on prognosis. (C) 2010 Elsevier Inc. All rights reserved. C1 [Klos, Coen L.; Shellito, Paul C.; Rattner, David W.; Hodin, Richard A.; Cusack, James C.; Bordeianou, Liliana; Sylla, Patricia; Hong, Theodore S.; Blaszkowsky, Lawrence; Ryan, Davis P.; Lauwers, Gregory Y.; Chang, Yuchiao; Berger, David L.] Massachusetts Gen Hosp, Div Gen & Gastrointestinal Surg, Boston, MA 02114 USA. [Klos, Coen L.] Univ Amsterdam, Dept Gastrointestinal Surg, Amsterdam, Netherlands. RP Berger, DL (reprint author), Massachusetts Gen Hosp, Div Gen & Gastrointestinal Surg, 15 Parkman St,WAC 460, Boston, MA 02114 USA. EM dberger@partners.org NR 18 TC 13 Z9 14 U1 0 U2 2 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD OCT PY 2010 VL 200 IS 4 BP 440 EP 445 DI 10.1016/j.amjsurg.2010.03.013 PG 6 WC Surgery SC Surgery GA 666JB UT WOS:000283109800002 PM 20887837 ER PT J AU Deshpande, V Oliva, E Young, RH AF Deshpande, Vikram Oliva, Esther Young, Robert H. TI Solid Pseudopapillary Neoplasm of the Ovary: A Report of 3 Primary Ovarian Tumors Resembling Those of the Pancreas SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE ovarian tumor; solid pseudopapillary neoplasm; pancreatic tumor ID BETA-CATENIN MUTATIONS; CELL TUMORS; CARCINOMA; VARIANT AB We report 3 cases of a hitherto undescribed ovarian tumor histologically and immunohistochemically identical to pancreatic solid pseudopapillary neoplasms. The patients were aged 17, 21, and 57 years of age. Two tumors involved the left ovary and 1 the right ovary. They ranged from 3 to 25.5 cm and were confined to the ovary. Radiologic investigations did not show an alternative primary site. Grossly the neoplasms were solid and cystic. On microscopic examination they had mostly diffuse and pseudopapillary growth patterns. Other patterns included nested and microcystic, including cysts filled with colloid-like material. The tumor cells were monotonous and the nuclei were round to oval with pale chromatin and occasional longitudinal nuclear grooves. Clear intracytoplasmic vacuoles were noted in 2 cases, and all 3 cases showed eosinophilic globules. Mitoses and atypia were virtually absent. Immunohistochemically, all 3 neoplasms showed intranuclear positivity for beta-catenin and loss of E-cadherin reactivity. All 3 tumors were negative for chromogranin, inhibin, and calretinin, although both cases evaluated for thyroglobulin were found negative. One patient has been followed for 6 years and is free of disease. The other 2 cases are recent. The tumors likely to enter into the differential diagnosis include sex-cord stromal tumors, steroid cell tumors, and struma ovarii. The morphologic and immunohistochemical similarity to pancreatic solid pseudopapillary neoplasm facilitates the accurate diagnosis of this rare ovarian neoplasm. C1 [Deshpande, Vikram] Harvard Univ, Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Dept Pathol,Med Sch, Boston, MA 02114 USA. RP Deshpande, V (reprint author), Harvard Univ, Massachusetts Gen Hosp, James Homer Wright Pathol Labs, Dept Pathol,Med Sch, 55 Fruit St, Boston, MA 02114 USA. EM vdeshpande@partners.org NR 22 TC 28 Z9 30 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD OCT PY 2010 VL 34 IS 10 BP 1514 EP 1520 DI 10.1097/PAS.0b013e3181f133e9 PG 7 WC Pathology; Surgery SC Pathology; Surgery GA 653WL UT WOS:000282128500015 PM 20871224 ER PT J AU Fusco, DN Downs, JA Satlin, MJ Pahuja, M Ramos, L Barie, PS Fleckenstein, L Murray, HW AF Fusco, Dahlene N. Downs, Jennifer A. Satlin, Michael J. Pahuja, Meera Ramos, Liz Barie, Philip S. Fleckenstein, Lawrence Murray, Henry W. TI Case Report: Non-Oral Treatment with Ivermectin for Disseminated Strongyloidiasis SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID HYPERINFECTION SYNDROME; SUBCUTANEOUS IVERMECTIN; PARENTERAL IVERMECTIN; STERCORALIS; SAFETY; THIABENDAZOLE; ALBENDAZOLE; INFECTIONS; EFFICACY; PATIENT AB Critically ill patients with disseminated strongyloidiasis may not be candidates for oral treatment. We report four patients with disseminated strongyloidiasis, believed to be unable to absorb oral therapy, who were treated with ivermectin by rectal and/or subcutaneous administration. Obtaining subcutaneous ivermectin and dosing it appropriately is a challenge. These cases underscore the need for improved access to subcutaneous ivermectin and more pharmacological data to guide use of this treatment approach. C1 [Downs, Jennifer A.; Satlin, Michael J.; Pahuja, Meera; Murray, Henry W.] New York Presbyterian Hosp, Weill Cornell Med Coll, Div Infect Dis, New York, NY USA. New York Presbyterian Hosp, Weill Cornell Med Coll, Dept Surg, New York, NY USA. [Barie, Philip S.] New York Presbyterian Hosp, Weill Cornell Med Coll, Dept Publ Hlth, New York, NY USA. [Ramos, Liz] New York Presbyterian Hosp, Dept Pharm, New York, NY USA. [Fleckenstein, Lawrence] Univ Iowa, Coll Pharm, Div Pharmacol & Expt Therapeut, Iowa City, IA 52242 USA. RP Fusco, DN (reprint author), Massachusetts Gen Hosp, 55 Fruit St, Boston, MA 02114 USA. EM dnfusco@partners.org; jna2002@med.cornell.edu; mjs9012@med.cornell.edu; mep2002@med.cornell.edu; lir9012@nyp.org; pbarie@med.cornell.edu; l-fleckenstein@uiowa.edu; hwmurray@med.cornell.edu OI Fleckenstein, Lawrence/0000-0001-5320-4531; Downs, Jennifer/0000-0001-9537-204X FU [T32 AI 007613]; [T32 HS000066] FX This study was supported by grants T32 AI 007613 (Dahlene N. Fusco, Michael J. Satlin, and Meera Pahuja) and T32 HS000066 (Jennifer A. Downs). NR 28 TC 8 Z9 8 U1 1 U2 2 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD OCT PY 2010 VL 83 IS 4 BP 879 EP 883 DI 10.4269/ajtmh.2010.10-0258 PG 5 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 663DF UT WOS:000282862500030 PM 20889884 ER PT J AU Livhits, M Mercado, C Yermilov, I Parikh, JA Dutson, E Mehran, A Ko, CY Gibbons, MM AF Livhits, Masha Mercado, Cheryl Yermilov, Irina Parikh, Janak A. Dutson, Erik Mehran, Amir Ko, Clifford Y. Gibbons, Melinda Maggard TI Behavioral Factors Associated with Successful Weight Loss after Gastric Bypass SO AMERICAN SURGEON LA English DT Article ID BARIATRIC SURGERY; FOLLOW-UP; QUESTIONNAIRE; ATTENDANCE; OBESITY AB Patients undergoing bariatric surgery lose substantial weight (>= 50% excess weight loss [EWL]), but an estimated 20 per cent fail to achieve this goal. Our objective was to identify behavioral predictors of weight loss after laparoscopic Roux-en-Y gastric bypass. We retrospectively surveyed 148 patients using validated instruments for factors predictive of weight loss. Success was defined as >= 50 per cent EWL and failure as <50 per cent EWL. Mean follow-up after laparoscopic Roux-en-Y gastric bypass was 40.1 +/- 15.3 months, with 52.7 per cent of patients achieving successful weight loss. After controlling for age, gender, and preoperative body mass index, predictors of successful weight loss included surgeon follow-up (odds ratio [OR] 8.2, P < 0.01), attendance of postoperative support groups (OR 3.7, P = 0.02), physical activity (OR 3.5, P < 0.01), single or divorced marital status (OR 3.2, P = 0.03), self-esteem (OR 0.3, P = 0.02), and binge eating (OR 0.9, P < 0.01). These factors should be addressed in prospective studies of weight loss after bariatric surgery, as they may identify patients at risk for weight loss failure who may benefit from early tailored interventions. C1 [Livhits, Masha; Mercado, Cheryl; Yermilov, Irina; Parikh, Janak A.; Dutson, Erik; Mehran, Amir; Ko, Clifford Y.; Gibbons, Melinda Maggard] Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, Los Angeles, CA 90095 USA. [Livhits, Masha; Yermilov, Irina; Parikh, Janak A.; Ko, Clifford Y.; Gibbons, Melinda Maggard] VA Greater Los Angeles Healthcare Syst, Dept Surg, Los Angeles, CA USA. [Gibbons, Melinda Maggard] Olive View Univ Calif, Dept Surg, Sylmar, CA USA. RP Livhits, M (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Surg, 10833 LeConte Ave,72 215 CHS, Los Angeles, CA 90095 USA. EM mlivhits@mednet.ucla.edu FU VA Department of Surgery; Robert Wood Johnson Physician Faculty FX We would like to acknowledge the generous contribution of Paul G. Shekelle to the design of our project and critical review of the analysis. The VA Department of Surgery provided support for Dr. Livhits and Dr. Maggard Gibbons. Dr. Maggard Gibbons's time was supported in part by a grant from the Robert Wood Johnson Physician Faculty Scholars program. NR 15 TC 43 Z9 44 U1 0 U2 7 PU SOUTHEASTERN SURGICAL CONGRESS PI ATLANTA PA 141 WEST WIEUCA RD, STE B100, ATLANTA, GA 30342 USA SN 0003-1348 J9 AM SURGEON JI Am. Surg. PD OCT PY 2010 VL 76 IS 10 BP 1139 EP 1142 PG 4 WC Surgery SC Surgery GA 663AO UT WOS:000282855600027 PM 21105629 ER PT J AU Royce-Nagel, G Cudkowicz, M Myers, D Nicholson, K Shui, A Schoenfeld, D Huang, XD Brown, RH AF Royce-Nagel, Galen Cudkowicz, Merit Myers, Daniela Nicholson, Katherine Shui, Amy Schoenfeld, David Huang, Xudong Brown, Robert H., Jr. TI Vanadium, aluminum, magnesium and manganese are not elevated in hair samples in amyotrophic lateral sclerosis SO AMYOTROPHIC LATERAL SCLEROSIS LA English DT Letter ID AXONAL-TRANSPORT; LATHYRISM C1 [Brown, Robert H., Jr.] Univ Massachusetts, Sch Med, Dept Neurol, Worcester, MA 01655 USA. [Royce-Nagel, Galen; Cudkowicz, Merit; Myers, Daniela; Nicholson, Katherine] Massachusetts Gen Hosp, Neurol Clin Trials Unit, Charlestown, MA USA. [Huang, Xudong] Massachusetts Gen Hosp, Dept Psychiat, Charlestown, MA USA. [Brown, Robert H., Jr.] Massachusetts Gen Hosp, Day Lab, Charlestown, MA USA. RP Brown, RH (reprint author), Univ Massachusetts, Sch Med, Dept Neurol, 55 Lake Ave N, Worcester, MA 01655 USA. EM brownrhjr@aol.com NR 14 TC 2 Z9 2 U1 0 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1748-2968 EI 1471-180X J9 AMYOTROPH LATERAL SC JI Amyotroph. Lateral. Scler. PD OCT PY 2010 VL 11 IS 5 BP 492 EP 493 DI 10.3109/17482960903513167 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 665XC UT WOS:000283069200016 PM 20438306 ER PT J AU Fidkowski, CW Zheng, H Firth, PG AF Fidkowski, Christina W. Zheng, Hui Firth, Paul G. TI The Anesthetic Considerations of Tracheobronchial Foreign Bodies in Children: A Literature Review of 12,979 Cases SO ANESTHESIA AND ANALGESIA LA English DT Review ID PLAIN CHEST RADIOGRAPHY; CT VIRTUAL BRONCHOSCOPY; BODY ASPIRATION; RIGID BRONCHOSCOPY; FLEXIBLE BRONCHOSCOPY; PEDIATRIC-PATIENTS; FIBEROPTIC BRONCHOSCOPY; INTRAVENOUS ANESTHESIA; RADIOLOGICAL FINDINGS; DELAYED PRESENTATION AB Asphyxiation by an inhaled foreign body is a leading cause of accidental death among children younger than 4 years. We analyzed the recent epidemiology of foreign body aspiration and reviewed the current trends in diagnosis and management. In this article, we discuss anesthetic management of bronchoscopy to remove objects. The reviewed articles total 12,979 pediatric bronchoscopies. Most aspirated foreign bodies are organic materials (81%, confidence interval [CI] = 77%-86%), nuts and seeds being the most common. The majority of foreign bodies (88%, CI = 85%-91%) lodge in the bronchial tree, with the remainder catching in the larynx or trachea. The incidence of right-sided foreign bodies (52%, CI = 48%-55%) is higher than that of left-sided foreign bodies (33%, CI = 30%-37%). A small number of objects fragment and lodge in different parts of the airways. Only 11% (CI = 8%-16%) of the foreign bodies were radio-opaque on radiograph, with chest radiographs being normal in 17% of children (CI = 13%-22%). Although rigid bronchoscopy is the traditional diagnostic "gold standard," the use of computerized tomography, virtual bronchoscopy, and flexible bronchoscopy is increasing. Reported mortality during bronchoscopy is 0.42%. Although asphyxia at presentation or initial emergency bronchoscopy causes some deaths, hypoxic cardiac arrest during retrieval of the object, bronchial rupture, and unspecified intraoperative complications in previously stable patients constitute the majority of in-hospital fatalities. Major complications include severe laryngeal edema or bronchospasm requiring tracheotomy or reintubation, pneumothorax, pneumomediastinum, cardiac arrest, tracheal or bronchial laceration, and hypoxic brain damage (0.96%). Aspiration of gastric contents is not reported. Preoperative assessment should determine where the aspirated foreign body has lodged, what was aspirated, and when the aspiration occurred ("what, where, when"). The choices of inhaled or IV induction, spontaneous or controlled ventilation, and inhaled or IV maintenance may be individualized to the circumstances. Although several anesthetic techniques are effective for managing children with foreign body aspiration, there is no consensus from the literature as to which technique is optimal. An induction that maintains spontaneous ventilation is commonly practiced to minimize the risk of converting a partial proximal obstruction to a complete obstruction. Controlled ventilation combined with IV drugs and paralysis allows for suitable rigid bronchoscopy conditions and a consistent level of anesthesia. Close communication between the anesthesiologist, bronchoscopist, and assistants is essential. (Anesth Analg 2010;111:1016-25) C1 [Fidkowski, Christina W.; Firth, Paul G.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Zheng, Hui] Massachusetts Gen Hosp, Ctr Biostat, Boston, MA 02114 USA. [Firth, Paul G.] Massachusetts Eye & Ear Infirm, Dept Anesthesia, Boston, MA 02114 USA. RP Firth, PG (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. EM pfirth@partners.org FU Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston; Department of Anesthesia, Massachusetts Eye and Ear Infirmary, Boston FX Statistical and administrative support funded by the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, and the Department of Anesthesia, Massachusetts Eye and Ear Infirmary, Boston. NR 79 TC 59 Z9 67 U1 2 U2 13 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 OCT PY 2010 VL 111 IS 4 BP 1016 EP 1025 DI 10.1213/ANE.0b013e3181ef3e9c PG 10 WC Anesthesiology SC Anesthesiology GA 656EY UT WOS:000282310200032 PM 20802055 ER PT J AU Wang, TT Kwon, HS Dai, GP Wang, RP Mijailovich, SM Moss, RL So, PTC Wedeen, VJ Gilbert, RJ AF Wang, Teresa T. Kwon, Hyuk Sang Dai, Guangping Wang, Ruopeng Mijailovich, Srboljub M. Moss, Richard L. So, Peter T. C. Wedeen, Van J. Gilbert, Richard J. TI Resolving Myoarchitectural Disarray in the Mouse Ventricular Wall with Diffusion Spectrum Magnetic Resonance Imaging (vol 38, pg 2841, 2010) SO ANNALS OF BIOMEDICAL ENGINEERING LA English DT Correction C1 [Gilbert, Richard J.] Caritas St Elizabeths Med Ctr, Dept Med, Brighton, MA 02135 USA. [Wang, Teresa T.; Kwon, Hyuk Sang; So, Peter T. C.] MIT, Dept Biol Engn, Cambridge, MA 02139 USA. [Dai, Guangping; Wang, Ruopeng; Wedeen, Van J.] Massachusetts Gen Hosp, Martinos Ctr Biomed Imaging, Charlestown, MA USA. [Mijailovich, Srboljub M.] Harvard Univ, Sch Publ Hlth, Physiol Program, Boston, MA 02115 USA. [Moss, Richard L.] Univ Wisconsin, Dept Physiol, Madison, WI 53706 USA. RP Gilbert, RJ (reprint author), Caritas St Elizabeths Med Ctr, Dept Med, 736 Cambridge St, Brighton, MA 02135 USA. EM richard.gilbert@caritaschristi.org NR 1 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0090-6964 J9 ANN BIOMED ENG JI Ann. Biomed. Eng. PD OCT PY 2010 VL 38 IS 10 BP 3269 EP 3269 DI 10.1007/s10439-010-0136-x PG 1 WC Engineering, Biomedical SC Engineering GA 650ZX UT WOS:000281895500022 ER PT J AU Monas, J Peak, DA AF Monas, Jessica Peak, David A. TI Spontaneous Tension Pneumocephalus Resulting From a Scalp Fistula in a Patient With a Remotely Placed Ventriculoperitoneal Shunt SO ANNALS OF EMERGENCY MEDICINE LA English DT Article ID NORMAL-PRESSURE HYDROCEPHALUS; PERITONEAL SHUNT; MANEUVER; SURGERY AB Tension pneumocephalus is a life-threatening condition that requires rapid recognition and intervention. It usually occurs as an early postoperative complication after neurosurgery or after trauma. Delayed tension pneumocephalus after ventriculoperitoneal shunt placement is unusual, with fewer than 50 published case reports, and is rarely caused by a scalp defect. We present a patient with nontraumatic tension pneumocephalus caused by a scalp fistula from a remote ventriculoperitoneal shunt placed 5 years earlier. This case is unique in that the patient underwent percutaneous aspiration of the tension pneumocephalus as a lifesaving procedure in the emergency department, with complete resolution of her symptoms at 30-day follow-up. [Ann Emerg Med. 2010;56:378-381.] C1 [Monas, Jessica; Peak, David A.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. RP Monas, J (reprint author), Massachusetts Gen Hosp, Dept Emergency Med, 5 Emerson Pl,Suite 100, Boston, MA 02114 USA. EM jmonas@partners.org FU Annals policy FX Funding and support: By Annals policy, all authors are required to disclose any and all commercial, financial, and other relationships in any way related to the subject of this article that might create any potential conflict of interest. The authors have stated that no such relationships exist. See the Manuscript Submission Agreement in this issue for examples of specific conflicts covered by this statement. NR 18 TC 4 Z9 4 U1 0 U2 0 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 OCT PY 2010 VL 56 IS 4 BP 378 EP 381 DI 10.1016/j.annemergmed.2010.05.030 PG 4 WC Emergency Medicine SC Emergency Medicine GA 663AD UT WOS:000282854500013 PM 20619934 ER PT J AU Smith, HP Hutson, R Alpert, GP Strote, J AF Smith, Hayden P. Hutson, Range Alpert, Geoffrey P. Strote, Jared TI Reporting Use of Force Injuries by Law Enforcement Officers in the Emergency Department SO ANNALS OF EMERGENCY MEDICINE LA English DT Editorial Material ID PHYSICIANS C1 [Smith, Hayden P.] Univ S Carolina, Dept Criminol & Criminal Justice, Currell Coll, Columbia, SC 29208 USA. [Hutson, Range] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Emergency Med, Boston, MA USA. [Strote, Jared] Univ Washington, Div Emergency Med, Seattle, WA 98195 USA. RP Smith, HP (reprint author), Univ S Carolina, Dept Criminol & Criminal Justice, Currell Coll, Room 207,1305 Greene St, Columbia, SC 29208 USA. EM smithhp@mailbox.sc.edu NR 10 TC 7 Z9 7 U1 0 U2 2 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 OCT PY 2010 VL 56 IS 4 BP 424 EP 425 DI 10.1016/j.annemergmed.2010.06.009 PG 2 WC Emergency Medicine SC Emergency Medicine GA 663AD UT WOS:000282854500020 PM 20868909 ER PT J AU Dierksen, GA Skehan, ME Khan, MA Jeng, J Nandigam, RNK Becker, JA Kumar, A Neal, KL Betensky, RA Frosch, MP Rosand, J Johnson, KA Viswanathan, A Salat, DH Greenberg, SM AF Dierksen, Gregory A. Skehan, Maureen E. Khan, Muhammad A. Jeng, Jed Nandigam, R. N. Kaveer Becker, John A. Kumar, Ashok Neal, Krista L. Betensky, Rebecca A. Frosch, Matthew P. Rosand, Jonathan Johnson, Keith A. Viswanathan, Anand Salat, David H. Greenberg, Steven M. TI Spatial Relation Between Microbleeds and Amyloid Deposits in Amyloid Angiopathy SO ANNALS OF NEUROLOGY LA English DT Article ID PITTSBURGH COMPOUND-B; CEREBRAL MICROBLEEDS; ALZHEIMERS-DISEASE; BRAIN; BETA; IMMUNOTHERAPY; DEMENTIA AB Advanced cerebrovascular beta-amyloid deposition (cerebral amyloid angiopathy, CAA) is associated with cerebral microbleeds, but the precise relationship between CAA burden and microbleeds is undefined. We used T2(star)-weighted magnetic resonance imaging (MRI) and noninvasive amyloid imaging with Pittsburgh Compound B (PiB) to analyze the spatial relationship between CAA and microbleeds. On coregistered positron emission tomography (PET) and MRI images, PiB retention was increased at microbleed sites compared to simulated control lesions (p = 0.002) and declined with increasing distance from the microbleed (p < 0.0001). These findings indicate that microbleeds occur preferentially in local regions of concentrated amyloid and support therapeutic strategies aimed at reducing vascular amyloid deposition. ANN NEUROL 2010;68:545-548 C1 [Dierksen, Gregory A.; Skehan, Maureen E.; Khan, Muhammad A.; Jeng, Jed; Nandigam, R. N. Kaveer; Kumar, Ashok; Rosand, Jonathan; Viswanathan, Anand; Greenberg, Steven M.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Hemorrhag Stroke Res Program,Dept Neurol, Boston, MA 02115 USA. [Becker, John A.; Johnson, Keith A.; Salat, David H.] Harvard Univ, Sch Med, Dept Radiol, Massachusetts Gen Hosp, Boston, MA 02115 USA. [Betensky, Rebecca A.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. [Frosch, Matthew P.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, CS Kubik Lab Neuropathol, Boston, MA USA. RP Greenberg, SM (reprint author), MGH Stroke Res Program, 55 Fruit St,CPZ 175,Suite 300, Boston, MA 02114 USA. EM sgreenberg@partners.org FU National Institutes of Health [R01 AG026484]; Alzheimer's Association [IIRG-06-26331]; Harvard NeuroDiscovery Center (HNDC) FX This work was supported by grants from the National Institutes of Health (R01 AG026484) and the Alzheimer's Association (IIRG-06-26331) and by the Harvard NeuroDiscovery Center (HNDC). NR 21 TC 98 Z9 104 U1 1 U2 2 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 OCT PY 2010 VL 68 IS 4 BP 545 EP 548 DI 10.1002/ana.22099 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 670CN UT WOS:000283398600016 PM 20865701 ER PT J AU Gardner, RC Schmahmann, JD AF Gardner, Raquel C. Schmahmann, Jeremy D. TI Is Arginine Test a Reliable Tool for Differential Diagnosis of Multiple System Atrophy? Reply SO ANNALS OF NEUROLOGY LA English DT Letter ID PARKINSONS-DISEASE C1 [Gardner, Raquel C.; Schmahmann, Jeremy D.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. RP Gardner, RC (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. NR 4 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 OCT PY 2010 VL 68 IS 4 BP 565 EP 566 DI 10.1002/ana.22147 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 670CN UT WOS:000283398600024 ER PT J AU Magnani, JW Johnson, VM Sullivan, LM Lubitz, SA Schnabel, RB Ellinor, PT Benjamin, EJ AF Magnani, Jared W. Johnson, Victor M. Sullivan, Lisa M. Lubitz, Steven A. Schnabel, Renate B. Ellinor, Patrick T. Benjamin, Emelia J. TI P-Wave Indices: Derivation of Reference Values from the Framingham Heart Study SO ANNALS OF NONINVASIVE ELECTROCARDIOLOGY LA English DT Article DE electrocardiogram; P waves; epidemiology; reference values ID GENERAL-HOSPITAL POPULATION; ATRIAL-FIBRILLATION; INTERATRIAL BLOCK; RISK PROFILE; DISPERSION; INTERVAL; ELECTROCARDIOGRAM; HYPERTENSION; PREVALENCE; FAILURE AB Methods: We randomly selected 20 men and 20 women from 10-year age intervals between < 25 years to 76-85 years from the Framingham Heart Study Original and Offspring Cohorts, excluding subjects with prevalent cardiovascular disease, hypertension, diabetes or obesity. The total included 295 subjects; eligibility in women > 75 years was limited by exclusion criteria. We used a digital measurement technique with demonstrated intrarater reproducibility to determine P-wave indices. P-wave indices examined included the maximum, mean, lead II and PR durations, dispersion, and the standard deviation of duration. Results: All P-wave indices were significantly (P < 0.0001) correlated with advancing age. Means of all P-wave indices were lower in women as compared to men. PR-interval duration was strongly correlated with maximum, mean, and lead II mean P-wave durations. In multivariable models adjusting for significant anthropometric and clinical associations risk factors, significant differences persisted by age and sex in P-wave indices. Conclusions. In our healthy sample without cardiovascular disease, hypertension, diabetes, or obesity, men and older subjects had longer mean P-wave indices. Our description of P-wave indices establishes reference values for future comparative studies and facilitates the classification of P-wave indices. Ann Noninvasive Electrocardiol 2010;15(4):344-352. C1 [Magnani, Jared W.; Benjamin, Emelia J.] Boston Univ, Sch Med, Sect Cardiovasc Med, Boston, MA 02118 USA. [Magnani, Jared W.; Benjamin, Emelia J.] NHLBI, Framingham Heart Study, Framingham, MA USA. [Johnson, Victor M.; Sullivan, Lisa M.] Boston Univ, Sch Publ Hlth, Dept Stat, Boston, MA USA. [Lubitz, Steven A.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiac Arrhythmia Serv, Boston, MA 02114 USA. [Lubitz, Steven A.; Ellinor, Patrick T.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Schnabel, Renate B.] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Mainz, Germany. [Benjamin, Emelia J.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA. [Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. RP Benjamin, EJ (reprint author), Boston Univ, Sch Med & Publ Hlth, Framingham Heart Study, 73 Mt Wayte Ave, Framingham, MA 01702 USA. EM emelia@bu.edu RI Schnabel, Renate/F-6527-2014; OI Sullivan, Lisa/0000-0003-0726-7149; Benjamin, Emelia/0000-0003-4076-2336 FU American Heart Association [09FTF2190028, RC1 HL101056, HL092577] FX Funding: This research was funded by American Heart Association Award 09FTF2190028; RC1 HL101056; HL092577. NR 29 TC 15 Z9 15 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1082-720X J9 ANN NONINVAS ELECTRO JI Ann. Noninvasive Electrocardiol. PD OCT PY 2010 VL 15 IS 4 BP 344 EP 352 DI 10.1111/j.1542-474X.2010.00390.x PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 666BG UT WOS:000283082200008 PM 20946557 ER PT J AU Batchelor, T Mulholland, P Neyns, B Nabors, LB Campone, M Wick, A Mason, W Xu, J Liu, Q van den Bent, M AF Batchelor, T. Mulholland, P. Neyns, B. Nabors, L. B. Campone, M. Wick, A. Mason, W. Xu, J. Liu, Q. van den Bent, M. TI A PHASE III RANDOMIZED STUDY COMPARING THE EFFICACY OF CEDIRANIB AS MONOTHERAPY, AND IN COMBINATION WITH LOMUSTINE, WITH LOMUSTINE ALONE IN RECURRENT GLIOBLASTOMA PATIENTS SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 35th European-Society-for-Medical-Oncology (ESMO) Congress CY OCT 08-12, 2010 CL Milan, ITALY SP European Soc Med Oncol C1 [Batchelor, T.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Mulholland, P.] UCL, London, England. [Neyns, B.] Univ Ziekenhuis Brussel, Brussels, Belgium. [Nabors, L. B.] Univ Alabama, Neurooncol Program, Birmingham, AL USA. [Campone, M.] Ctr Rene Gauducheau, St Herblain, France. [Wick, A.] Univ Heidelberg, Heidelberg, Germany. [Mason, W.] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. [Mason, W.] Univ Toronto, Toronto, ON, Canada. [Xu, J.; Liu, Q.] AstraZeneca, Wilmington, DE USA. [van den Bent, M.] Erasme Univ Hosp, Daniel den Hoed Canc Ctr, Rotterdam, Netherlands. NR 0 TC 9 Z9 9 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD OCT PY 2010 VL 21 SU 8 BP 4 EP 4 PG 1 WC Oncology SC Oncology GA 666LE UT WOS:000283115900008 ER PT J AU Mok, T Spigel, DR Park, K Socinski, MA Tung, SY Kim, DW Ou, SHI Zhang, H O'Connell, JP Janne, P AF Mok, T. Spigel, D. R. Park, K. Socinski, M. A. Tung, S. Y. Kim, D-W Ou, S-H. I. Zhang, H. O'Connell, J. P. Jaenne, P. TI EFFICACY AND SAFETY OF PF299804 AS FIRST-LINE TREATMENT (TX) OF PATIENTS (PTS) WITH ADVANCED (ADV) NSCLC SELECTED FOR ACTIVATING MUTATION (MU) OF EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 35th European-Society-for-Medical-Oncology (ESMO) Congress CY OCT 08-12, 2010 CL Milan, ITALY SP European Soc Med Oncol C1 [Mok, T.] Chinese Univ Hong Kong, Shatin, Hong Kong, Peoples R China. [Spigel, D. R.] SCRI, Nashville, TN USA. [Park, K.] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Seoul, South Korea. [Socinski, M. A.] Univ N Carolina, Chapel Hill, NC USA. [Tung, S. Y.] Tuen Mun Hosp, Tuen Mun, Hong Kong, Peoples R China. [Kim, D-W] Seoul Natl Univ, Seoul, South Korea. [Ou, S-H. I.] Univ Calif Irvine, Sch Med, Irvine, CA 92717 USA. [Zhang, H.] Pfizer China Res & Dev Co Ltd, Shanghai, Peoples R China. [O'Connell, J. P.] Pfizer Oncol, New London, CT USA. [Jaenne, P.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 13 Z9 13 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD OCT PY 2010 VL 21 SU 8 BP 8 EP 8 PG 1 WC Oncology SC Oncology GA 666LE UT WOS:000283115900019 ER PT J AU Kaye, SB Fehrenbacher, L Holloway, R Horowitz, N Karlan, B Amit, A Slomovitz, B Chang, I Yauch, RL Reddy, JC AF Kaye, S. B. Fehrenbacher, L. Holloway, R. Horowitz, N. Karlan, B. Amit, A. Slomovitz, B. Chang, I. Yauch, R. L. Reddy, J. C. TI A PHASE 2, RANDOMIZED, PLACEBO-CONTROLLED STUDY OF HEDGEHOG (HH) PATHWAY INHIBITOR GDC-0449 AS MAINTENANCE THERAPY IN PATIENTS WITH OVARIAN CANCER IN 2(ND) OR 3(RD) COMPLETE REMISSION (CR) SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 35th Annual Meeting of the European-Society-for-Medical-Oncology (ESMO) CY OCT 08-12, 2010 CL Milan, ITALY SP European Soc Med Oncol (ESMO) C1 [Kaye, S. B.] Royal Marsden Hosp, Sutton, Surrey, England. [Fehrenbacher, L.] Kaiser Permanente Med Ctr, Vallejo, CA USA. [Holloway, R.] Florida Hosp, Inst Canc, Orlando, FL USA. [Horowitz, N.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Karlan, B.] Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. [Amit, A.] Rambam Med Ctr, Haifa, Israel. [Slomovitz, B.] Morristown Mem Hosp, Morristown, NJ USA. [Chang, I.; Yauch, R. L.; Reddy, J. C.] Genentech Inc, San Francisco, CA USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD OCT PY 2010 VL 21 SU 8 BP 11 EP 11 PG 1 WC Oncology SC Oncology GA 666LE UT WOS:000283115900026 ER PT J AU Baselga, J AF Baselga, J. TI Treatment of HER2-overexpressing breast cancer SO ANNALS OF ONCOLOGY LA English DT Article DE Breast cancer; HER2; monoclonal antibodies; tyrosine kinase inhibitors; resistance ID GROWTH-FACTOR RECEPTOR; PHASE-II TRIAL; METASTATIC BREAST; MONOCLONAL-ANTIBODY; ADJUVANT CHEMOTHERAPY; TUMOR-GROWTH; TRASTUZUMAB; LAPATINIB; INHIBITOR; HER2 AB The HER family of receptors consists of four closely related type 1 transmembrane TK receptors: HER1 (EGFR), HER2, HER3 and HER4. Signalling via the HER family of receptors underpins the majority of the intricate array of cellular activities on which cell survival and functionality depend. Aberrant HER2 expression and/or functionality have been implicated in the evolution of breast cancer and this receptor has proved to be a potent target for anticancer therapies, including antibody-based therapies to prevent ligand binding, dimer formation or the recruitment of antibody-dependent cell-mediated cytotoxicity, and direct kinase inhibition to prevent molecular activation and recruitment of downstream signalling partners. Novel strategies against HER2 include HER tyrosine kinase inhibitors, HSP90 inhibitors and antibody-chemotherapy conjugates. This latter approach is exemplified by T-DM1, a potent antibody that has a good safety profile and that has shown remarkable activity in patients with advanced disease. In addition, pertuzumab, an mAb that directly inhibits the formation of HER2 dimers including the HER2:HER3 dimer, offers a unique mechanism of HER3 inhibition. All these approaches have shown substantial clinical activity in patients refractory to trastuzumab. It is anticipated that with the increased availability of novel anti-HER2 agents together with a better understanding of the mechanisms of resistance to anti-HER2 agents we should be able to further improve the outcome of patients with HER2 breast cancer. There will also be an increasing tendency towards moving the study of these agents to earlier stages of the disease, namely in the adjuvant and neoadjuvant setting. C1 Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. RP Baselga, J (reprint author), Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. EM jbaselga@partners.org NR 35 TC 54 Z9 55 U1 3 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD OCT PY 2010 VL 21 SU 7 BP 36 EP 40 DI 10.1093/annonc/mdq421 PG 5 WC Oncology SC Oncology GA 666FK UT WOS:000283099200004 ER PT J AU Tsao, M Hainaut, P Bourredjem, A Janne, PA Pignon, J Douillard, J Soria, J Seymour, L Shepherd, FA AF Tsao, M. Hainaut, P. Bourredjem, A. Janne, P. A. Pignon, J. Douillard, J. Soria, J. Seymour, L. Shepherd, F. A. TI LACE-BIO POOLED ANALYSIS OF THE PROGNOSTIC AND PREDICTIVE VALUE OF KRAS MUTATION IN COMPLETELY RESECTED NON-SMALL CELL LUNG CANCER (NSCLC) SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 35th European-Society-for-Medical-Oncology (ESMO) Congress CY OCT 08-12, 2010 CL Milan, ITALY SP European Soc Med Oncol C1 [Tsao, M.] Princess Margaret Hosp, Dept Pathol, Toronto, ON M4X 1K9, Canada. [Hainaut, P.] Int Agcy Res Canc, Mol Carcinogenesis & Biomarkers Grp, F-69372 Lyon, France. [Soria, J.] Inst Cancerol Gustave Roussy, Dept Med, Villejuif, France. [Janne, P. A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Pignon, J.] Inst Gustave Roussy, Villejuif, France. [Douillard, J.] Ctr Rene Gauducheau, F-44035 Nantes, France. [Seymour, L.] NCIC Clin Trials Grp, Kingston, ON, Canada. NR 0 TC 8 Z9 8 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD OCT PY 2010 VL 21 SU 8 BP 63 EP 63 PG 1 WC Oncology SC Oncology GA 666LE UT WOS:000283115900174 ER PT J AU Krop, I LoRusso, P Miller, KD Modi, S Yardley, D Rodriguez, G Lu, M Burington, B Agresta, S Rugo, H AF Krop, I. LoRusso, P. Miller, K. D. Modi, S. Yardley, D. Rodriguez, G. Lu, M. Burington, B. Agresta, S. Rugo, H. TI A PHASE 2 STUDY OF THE HER2 ANTIBODY-DRUG CONJUGATE TRASTUZUMAB-DM1 (T-DM1) IN PATIENTS (PTS) WITH HER2-POSITIVE METASTATIC BREAST CANCER (MBC) PREVIOUSLY TREATED WITH TRASTUZUMAB, LAPATINIB, AND CHEMOTHERAPY SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 35th European-Society-for-Medical-Oncology (ESMO) Congress CY OCT 08-12, 2010 CL Milan, ITALY SP European Soc Med Oncol C1 [Krop, I.] Dana Farber Canc Inst, Boston, MA 02115 USA. [LoRusso, P.] Karmanos Canc Inst, Detroit, MI USA. [Miller, K. D.] Indiana Univ, Melvin & Bren Simon Canc Ctr, Indianapolis, IN 46204 USA. [Modi, S.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Yardley, D.] Sarah Cannon Res Inst, Nashville, TN USA. [Rodriguez, G.] S Texas Oncol Hematol, San Antonio, TX USA. [Lu, M.; Burington, B.; Agresta, S.] Genentech Inc, San Francisco, CA USA. [Rugo, H.] UCSF, Ctr Comprehens Canc, San Francisco, CA USA. NR 0 TC 6 Z9 7 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD OCT PY 2010 VL 21 SU 8 BP 97 EP 97 PG 1 WC Oncology SC Oncology GA 666LE UT WOS:000283115900294 ER PT J AU Phan, S Duenne, A Gray, R Miller, K AF Phan, S. Duenne, A. Gray, R. Miller, K. TI OUTCOMES FOR METASTATIC BREAST CANCER PATIENTS CONTINUING ON BEVACIZUMAB ALONE IN STUDY E2100 SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 35th European-Society-for-Medical-Oncology (ESMO) Congress CY OCT 08-12, 2010 CL Milan, ITALY SP European Soc Med Oncol C1 [Phan, S.] Genentech Inc, Biooncol, San Francisco, CA USA. [Duenne, A.] F Hoffmann La Roche Ltd, Basel, Switzerland. [Gray, R.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Miller, K.] Indiana Univ, Melvin & Bren Simon Canc Ctr, Indianapolis, IN 46204 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD OCT PY 2010 VL 21 SU 8 BP 98 EP 98 PG 1 WC Oncology SC Oncology GA 666LE UT WOS:000283115900297 ER PT J AU Colleoni, M Giobbie-Hurder, A AF Colleoni, M. Giobbie-Hurder, A. TI Benefits and adverse effects of endocrine therapy SO ANNALS OF ONCOLOGY LA English DT Article DE adjuvant treatment; early breast cancer; endocrine therapy; side effects ID EARLY-BREAST-CANCER; INTERNATIONAL EXPERT CONSENSUS; POSTMENOPAUSAL WOMEN; ADJUVANT TAMOXIFEN; RANDOMIZED-TRIALS; PREMENOPAUSAL PATIENTS; AROMATASE INHIBITORS; CLINICAL-TRIAL; YOUNG-WOMEN; CHEMOTHERAPY AB Endocrine-responsive tumors that are small and without nodal involvement (i.e. tumors classified as pT1 pN0) are a heterogeneous group of tumors that are associated with a low risk of relapse in the majority of the cases. Therefore, the costs and benefits of adjuvant endocrine therapy should be carefully considered within this subgroup of patients. Treatment decisions should take into consideration co-morbidities as well as the presence of other classical risk factors such as HER2 overexpression or extensive peritumoral vascular invasion. Tamoxifen or tamoxifen plus ovarian function suppression should be considered as proper endocrine therapies in premenopausal patients. Ovarian function suppression alone or ovarian ablation might also be considered adequate in selected patients (e.g. very low-risk patients, in the presence of co-morbidities or patient preference). An aromatase inhibitor should form part of standard endocrine therapy for most postmenopausal women with receptor-positive breast cancer, although patients at low risk or with co-morbid musculoskeletal or cardiovascular risk factors may be considered suitable for tamoxifen alone. Tailored endocrine treatments should be considered in patients with endocrine-responsive tumors classified as pT1 pN0. Issues focusing on safety, quality of life and subjective side effects should be routinely discussed. C1 [Colleoni, M.] European Inst Oncol, Res Unit Med Senol, I-20141 Milan, Italy. [Colleoni, M.] European Inst Oncol, IBCSG, I-20141 Milan, Italy. [Giobbie-Hurder, A.] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat & Computat Biol,IBCSG,Stat Ctr, Boston, MA 02115 USA. RP Colleoni, M (reprint author), European Inst Oncol, Res Unit Med Senol, Via Ripamonti 435, I-20141 Milan, Italy. EM marco.colleoni@ieo.it FU Novartis; Pfizer; US National Cancer Institute [CA-75362] FX The IBCSG receives research funding from Novartis and Pfizer.; The IBCSG Statistical Center is partially supported by US National Cancer Institute grant CA-75362. NR 41 TC 14 Z9 15 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD OCT PY 2010 VL 21 SU 7 BP 107 EP 111 DI 10.1093/annonc/mdq281 PG 5 WC Oncology SC Oncology GA 666FK UT WOS:000283099200015 ER PT J AU Vahdat, LT Thomas, E Roche, H Hortobagyi, GN Sparano, J Yelle, L Fornier, MN Martin, M Bunnell, C Perez, E AF Vahdat, L. T. Thomas, E. Roche, H. Hortobagyi, G. N. Sparano, J. Yelle, L. Fornier, M. N. Martin, M. Bunnell, C. Perez, E. TI IXABEPILONE ( IXA)-ASSOCIATED PERIPHERAL NEUROPATHY (PN): RETROSPECTIVE REVIEW OF DATA FROM PHASE II AND III CLINICAL TRIALS SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 35th European-Society-for-Medical-Oncology (ESMO) Congress CY OCT 08-12, 2010 CL Milan, ITALY SP European Soc Med Oncol C1 [Vahdat, L. T.] Weill Cornell Breast Ctr, Dept Med Oncol, New York, NY USA. [Thomas, E.] Kaiser Permanente, Oakland, CA USA. [Roche, H.] Inst Claudius Regaud, Toulouse, France. [Hortobagyi, G. N.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Sparano, J.] Albert Einstein Comprehens Canc Ctr, Bronx, NY USA. [Yelle, L.] Ctr Hosp Univ Montreal, Hop Notre Dame, Montreal, PQ, Canada. [Fornier, M. N.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Martin, M.] Hosp Gen Gregorio Maranon, Med Oncol Serv, Madrid, Spain. [Bunnell, C.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Perez, E.] Mayo Clin, Breast Ctr, Jacksonville, FL USA. RI Roche, Henri/O-9211-2014 OI Roche, Henri/0000-0001-7463-205X NR 0 TC 1 Z9 1 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD OCT PY 2010 VL 21 SU 8 BP 109 EP 110 PG 2 WC Oncology SC Oncology GA 666LE UT WOS:000283115900336 ER PT J AU Sequist, LV Akerley, WL Brugger, W Ferrari, D Garmey, E Gerber, DE Orlov, S Ramlau, R von Pawel, J Schiller, JH AF Sequist, L. V. Akerley, W. L. Brugger, W. Ferrari, D. Garmey, E. Gerber, D. E. Orlov, S. Ramlau, R. von Pawel, J. Schiller, J. H. TI FINAL RESULTS FROM ARQ 197-209: A GLOBAL RANDOMIZED PLACEBO-CONTROLLED PHASE 2 CLINICAL TRIAL OF ERLOTINIB PLUS ARQ 197 VERSUS ERLOTINIB PLUS PLACEBO IN PREVIOUSLY TREATED EGFR-INHIBITOR NAiVE PATIENTS WITH ADVANCED NON-SMALL CELL LUNG CANCER (NSCLC) SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 35th European-Society-for-Medical-Oncology (ESMO) Congress CY OCT 08-12, 2010 CL Milan, ITALY SP European Soc Med Oncol C1 [Sequist, L. V.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Akerley, W. L.] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT USA. [Brugger, W.] Schwarzwald Baar Klin, Villingen Schwenningen, Germany. [Ferrari, D.; Garmey, E.] ArQule Inc, Woburn, MA USA. [Gerber, D. E.; Schiller, J. H.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Orlov, S.] St Petersburg Pavlov State Med Univ, St Petersburg, Russia. [Ramlau, R.] Reg Ctr Lung Dis, Dept Oncol, Poznan, Poland. [von Pawel, J.] Asklepios Fachkliniken Muenchen Gauting, Gauting, Germany. NR 0 TC 8 Z9 8 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD OCT PY 2010 VL 21 SU 8 BP 122 EP 122 PG 1 WC Oncology SC Oncology GA 666LE UT WOS:000283115900378 ER PT J AU Camidge, DR Bang, Y Iafrate, AJ Kwak, EL Maki, RG Solomon, B Ou, SI Salgia, R Shaw, A Clark, J AF Camidge, D. R. Bang, Y. Iafrate, A. J. Kwak, E. L. Maki, R. G. Solomon, B. Ou, S. I. Salgia, R. Shaw, A. Clark, J. TI CLINICAL ACTIVITY OF CRIZOTINIB (PF-02341066), IN ALK-POSITIVE PATIENTS WITH NON-SMALL CELL LUNG CANCER (NSCLC) SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 35th European-Society-for-Medical-Oncology (ESMO) Congress CY OCT 08-12, 2010 CL Milan, ITALY SP European Soc Med Oncol C1 [Camidge, D. R.] Univ Colorado, Div Med Oncol, Aurora, CO USA. [Bang, Y.] Seoul Natl Univ Hosp, Seoul 110744, South Korea. [Iafrate, A. J.; Kwak, E. L.; Shaw, A.; Clark, J.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Maki, R. G.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. [Solomon, B.] Peter MacCallum Canc Ctr, Melbourne, Australia. [Ou, S. I.] Univ Calif Irvine, Irvine, CA USA. [Salgia, R.] Univ Chicago, Ctr Canc, Chicago, IL 60637 USA. NR 0 TC 0 Z9 0 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 OCT PY 2010 VL 21 SU 8 BP 123 EP 123 PG 1 WC Oncology SC Oncology GA 666LE UT WOS:000283115900381 ER PT J AU Yang, C Shih, J Su, W Hsia, T Sequist, LV Chang, G Calvo, R Cong, XJ Shahidi, M Miller, V AF Yang, C. Shih, J. Su, W. Hsia, T. Sequist, L. V. Chang, G. Calvo, R. Cong, X. J. Shahidi, M. Miller, V. TI A PHASE II STUDY OF BIBW 2992 IN PATIENTS WITH ADENOCARCINOMA OF THE LUNG AND ACTIVATING EGFR/HER1 MUTATIONS (LUX-LUNG 2) SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 35th European-Society-for-Medical-Oncology (ESMO) Congress CY OCT 08-12, 2010 CL Milan, ITALY SP European Soc Med Oncol C1 [Yang, C.] Natl Taiwan Univ Hosp, Dept Oncol, Taipei, Taiwan. [Su, W.] Natl Cheng Kung Univ Hosp, Tainan 70428, Taiwan. [Hsia, T.] China Med Univ Hosp, Taichung, Taiwan. [Sequist, L. V.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Chang, G.] Taichung Vet Gen Hosp, Dept Internal Med, Taichung, Taiwan. [Calvo, R.; Cong, X. J.] Boehringer Ingelheim Pharmaceut Inc, Ridgefield, CT 06877 USA. [Shahidi, M.] Boehringer Ingelheim Uk, Bracknell, Berks, England. [Miller, V.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NR 0 TC 12 Z9 12 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD OCT PY 2010 VL 21 SU 8 BP 123 EP 123 PG 1 WC Oncology SC Oncology GA 666LE UT WOS:000283115900382 ER PT J AU Lynch, TJ Neal, J Bondarenko, I Luft, A Serwatowski, P Barlesi, F Chacko, R Sebastian, M Cuillerot, J Reck, M AF Lynch, T. J., Jr. Neal, J. Bondarenko, I. Luft, A. Serwatowski, P. Barlesi, F. Chacko, R. Sebastian, M. Cuillerot, J. Reck, M. TI OVERALL SURVIVAL (OS) AND PROGRESSION FREE SURVIVAL (PFS) RESULTS FOR A RANDOMIZED PHASE 2 TRIAL OF IPILIMUMAB (IPI) AND PACLITAXEL/CARBOPLATIN (P/C) IN FIRST-LINE STAGE IIIB/IV NON-SMALL CELL LUNG CANCER (NSCLC) SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 35th European-Society-for-Medical-Oncology (ESMO) Congress CY OCT 08-12, 2010 CL Milan, ITALY SP European Soc Med Oncol C1 [Lynch, T. J., Jr.] Yale Univ, Ctr Canc, New Haven, CT USA. [Neal, J.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA 02114 USA. [Bondarenko, I.] Dnipropetrovsk Municipal Clin Hosp 4, Dept Oncol Radiodiagnosis & Radioth, Dnepropetrovsk, Ukraine. [Luft, A.] Leningrad Reg Clin Hosp, State Inst, St Petersburg, Russia. [Serwatowski, P.] Oddzial Chemioterapii, Szczecin, Poland. [Sebastian, M.] Johannes Gutenberg Univ Mainz, Mainz, Germany. [Cuillerot, J.] Bristol Myers Squibb Co, Global Clin Res, Wallingford, CT 06492 USA. [Reck, M.] Hosp Grosshansdorf, Grosshansdorf, Germany. [Barlesi, F.] Univ Mediterranee Assistance Publ Hapitaux Marsei, Marseille, France. [Chacko, R.] Christian Med Coll & Hosp, Vellore, Tamil Nadu, India. NR 0 TC 2 Z9 2 U1 1 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD OCT PY 2010 VL 21 SU 8 BP 126 EP 126 PG 1 WC Oncology SC Oncology GA 666LE UT WOS:000283115900390 ER PT J AU Bennouna, J Besse, B Leighl, NB Blais, N Traynor, AM Papadimitrakopoulou, V Klimovsky, J Jappe, A Jehl, V Johnson, BE AF Bennouna, J. Besse, B. Leighl, N. B. Blais, N. Traynor, A. M. Papadimitrakopoulou, V. Klimovsky, J. Jappe, A. Jehl, V. Johnson, B. E. TI EVEROLIMUS PLUS ERLOTINIB VERSUS ERLOTINIB ALONE IN PREVIOUSLY TREATED PATIENTS WITH ADVANCED NON-SMALL-CELL LUNG CANCER (NSCLC) SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 35th European-Society-for-Medical-Oncology (ESMO) Congress CY OCT 08-12, 2010 CL Milan, ITALY SP European Soc Med Oncol C1 [Bennouna, J.] Ctr Rene Gauducheau, St Herblain, France. [Besse, B.] Inst Gustave Roussy, Dept Med, Villejuif, France. [Leighl, N. B.] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. [Blais, N.] Hop Notre Dame De Bon Secours, CHUM, Montreal, PQ, Canada. [Traynor, A. M.] Univ Wisconsin, Carbone Canc Ctr, Madison, WI 53706 USA. [Papadimitrakopoulou, V.] Univ Texas Houston, Houston, TX USA. [Klimovsky, J.] Novartis Pharmaceut, Oncol, Florham Pk, NJ USA. [Jappe, A.; Jehl, V.] Novartis Pharma AG, Oncol, Basel, Switzerland. [Johnson, B. E.] Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA. RI bennouna, jaafar/K-9350-2015 NR 0 TC 2 Z9 2 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD OCT PY 2010 VL 21 SU 8 BP 140 EP 140 PG 1 WC Oncology SC Oncology GA 666LE UT WOS:000283115900434 ER PT J AU Bendell, JC Wagner, AJ Dolly, S Morgan, JA Papadatos-Pastos, D Ware, J Mazina, KE Lauchle, J Burris, H De Bono, J AF Bendell, J. C. Wagner, A. J. Dolly, S. Morgan, J. A. Papadatos-Pastos, D. Ware, J. Mazina, K. E. Lauchle, J. Burris, H. De Bono, J. TI A FIRST-IN-HUMAN PHASE I STUDY TO EVALUATE THE DUAL PI3K/MTOR INHIBITOR GDC-0980 ADMINISTERED QD IN PATIENTS WITH ADVANCED SOLID TUMORS OR NON-HODGKIN S LYMPHOMA (NHL) SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 35th European-Society-for-Medical-Oncology (ESMO) Congress CY OCT 08-12, 2010 CL Milan, ITALY SP European Soc Med Oncol C1 [Bendell, J. C.; Burris, H.] Sarah Cannon Res Inst, Nashville, TN USA. [Wagner, A. J.; Morgan, J. A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Papadatos-Pastos, D.; De Bono, J.] Royal Marsden Hosp, Inst Canc Res, Drug Dev Unit, Sutton, Surrey, England. [Mazina, K. E.] Genentech Inc, Res & Early Dev, San Francisco, CA 94080 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD OCT PY 2010 VL 21 SU 8 BP 162 EP 163 PG 2 WC Oncology SC Oncology GA 666LE UT WOS:000283115900509 ER PT J AU Wagner, AJ Tibes, R Shapiro, GI Iyengar, T Demetri, GD Weiss, GJ Fridlyand, J Mazina, KE Levy, GG Lorusso, PM AF Wagner, A. J. Tibes, R. Shapiro, G. I. Iyengar, T. Demetri, G. D. Weiss, G. J. Fridlyand, J. Mazina, K. E. Levy, G. G. Lorusso, P. M. TI A FIRST-IN-HUMAN PHASE I STUDY TO EVALUATE THE PAN-PI3K INHIBITOR GDC-0941 ADMINISTERED QD OR BID IN PATIENTS WITH ADVANCED SOLID TUMORS SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 35th European-Society-for-Medical-Oncology (ESMO) Congress CY OCT 08-12, 2010 CL Milan, ITALY SP European Soc Med Oncol C1 [Wagner, A. J.; Shapiro, G. I.; Demetri, G. D.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Tibes, R.; Iyengar, T.; Weiss, G. J.] Scottsdale Healthcare & TGen, Virginia G Piper Canc Ctr, Scottsdale, AZ USA. [Fridlyand, J.; Mazina, K. E.; Levy, G. G.] Genentech Inc, San Francisco, CA 94080 USA. [Lorusso, P. M.] Karmanos Canc Inst, Detroit, MI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD OCT PY 2010 VL 21 SU 8 BP 163 EP 163 PG 1 WC Oncology SC Oncology GA 666LE UT WOS:000283115900510 ER PT J AU Ewer, MS Suter, TM Lenihan, DJ Niculescu, L Breazna, A Demetri, GD Motzer, RJ AF Ewer, M. S. Suter, T. M. Lenihan, D. J. Niculescu, L. Breazna, A. Demetri, G. D. Motzer, R. J. TI CARDIOVASCULAR ADVERSE EVENTS (CV-AES) IN A POOLED ANALYSIS OF 1090 PATIENTS (PT) FROM PHASE 3 SUNITINIB (SU) TRIALS SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 35th European-Society-for-Medical-Oncology (ESMO) Congress CY OCT 08-12, 2010 CL Milan, ITALY SP European Soc Med Oncol C1 [Ewer, M. S.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA. [Suter, T. M.] Univ Hosp Bern, CH-3010 Bern, Switzerland. [Lenihan, D. J.] Vanderbilt Univ, Nashville, TN USA. [Niculescu, L.; Breazna, A.] Pfizer Oncol, New York, NY USA. [Demetri, G. D.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Motzer, R. J.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD OCT PY 2010 VL 21 SU 8 BP 166 EP 166 PG 1 WC Oncology SC Oncology GA 666LE UT WOS:000283115900519 ER PT J AU Blay, J Le Cesne, A Judson, I Schoffski, P Sessa, C Paz-Ares, L Hogberg, T Zintl, P Parekh, TV Demetri, GD AF Blay, J. Le Cesne, A. Judson, I. Schoffski, P. Sessa, C. Paz-Ares, L. Hogberg, T. Zintl, P. Parekh, T. V. Demetri, G. D. TI CHARACTERISATION OF THE HEPATIC SAFETY PROFILE OF TRABECTEDIN: POOLED ANALYSIS OF 19 PHASE II CLINICAL TRIALS (CTS) IN 1132 PATIENTS WITH SOLID TUMOURS SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 35th European-Society-for-Medical-Oncology (ESMO) Congress CY OCT 08-12, 2010 CL Milan, ITALY SP European Soc Med Oncol C1 [Blay, J.] Ctr Leon Berard, F-69373 Lyon, France. [Le Cesne, A.] Inst Gustave Roussy, Villejuif, France. [Judson, I.] Royal Marsden Hosp, CR UK Ctr Canc Therapeut, Sarcoma Unit, Sutton, Surrey, England. [Schoffski, P.] Catholic Univ Louvain, Leuven Canc Inst, Univ Hosp Leuven, Dept Gen Med Oncol, B-3000 Louvain, Belgium. [Sessa, C.] IOSI Oncol Inst So Switzerland, Div Oncol, Osped San Giovanni, Bellinzona, Switzerland. [Paz-Ares, L.] Virgen del Rocio Univ Hosp, Med Oncol Serv, Seville, Spain. [Hogberg, T.] Univ Lund Hosp, Dept Canc Epidemiol, Tumor Registry, S-22185 Lund, Sweden. [Zintl, P.] Colmenar Viejo, PharmaMar, Med Affairs, Madrid, Spain. [Parekh, T. V.] Centocor Ortho Biotech Prod LP, Raritan, NJ USA. [Demetri, G. D.] Dana Farber Harvard Canc Ctr, Ludwig Ctr, Ctr Sarcoma & Bone Oncol, Boston, MA USA. RI IBIS, NUEVAS TERAPIA/P-3415-2015; Blay, Jean-Yves/N-3966-2016 OI Blay, Jean-Yves/0000-0001-7190-120X NR 0 TC 1 Z9 1 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD OCT PY 2010 VL 21 SU 8 BP 177 EP 178 PG 2 WC Oncology SC Oncology GA 666LE UT WOS:000283115900555 ER PT J AU Rocha-Lima, C Shapiro, GI Hurwitz, H Montero, A Franklin, C Xiong, H Chiu, Y Krivoshik, AP Uronis, H AF Rocha-Lima, C. Shapiro, G. I. Hurwitz, H. Montero, A. Franklin, C. Xiong, H. Chiu, Y. Krivoshik, A. P. Uronis, H. TI COMBINATION STUDY OF NAVITOCLAX (ABT-263) WITH GEMCITABINE (G) IN PATIENTS (PTS) WITH SOLID TUMORS SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 35th European-Society-for-Medical-Oncology (ESMO) Congress CY OCT 08-12, 2010 CL Milan, ITALY SP European Soc Med Oncol C1 [Rocha-Lima, C.] Sylvester Comprehens Canc Ctr, Colorectal Pancreatohepatobiliary Programs, Miami, FL USA. [Rocha-Lima, C.; Montero, A.] Univ Miami, Miami, FL USA. [Shapiro, G. I.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Hurwitz, H.; Uronis, H.] Duke Univ, Med Ctr, Durham, NC USA. [Franklin, C.; Krivoshik, A. P.] Abbott, Abbott Pk, IL USA. [Xiong, H.] Abbott Labs, Clin Pharmacokinet & Pharmacodynam, Abbott Pk, IL 60064 USA. [Chiu, Y.] Abbott Labs, Clin Pharmacol & Pharmacometr, Abbott Pk, IL 60064 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD OCT PY 2010 VL 21 SU 8 BP 181 EP 181 PG 1 WC Oncology SC Oncology GA 666LE UT WOS:000283115900568 ER PT J AU Kindler, H Richards, D Stephenson, J Garbo, L Garon, E Lima, CR Safran, H Feigal, E Bray, S Fuchs, C AF Kindler, H. Richards, D. Stephenson, J. Garbo, L. Garon, E. Lima, C. Rocha Safran, H. Feigal, E. Bray, S. Fuchs, C. TI CONATUMUMAB (CON) OR AMG 479 OR PLACEBO (PBO) plus GEMCITABINE (GEM) IN PATIENTS (PTS) WITH METASTATIC PANCREATIC CANCER (MPC): A PLACEBO-CONTROLLED, RANDOMIZED, PHASE 2 STUDY SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 35th European-Society-for-Medical-Oncology (ESMO) Congress CY OCT 08-12, 2010 CL Milan, ITALY SP European Soc Med Oncol C1 [Kindler, H.] Univ Chicago, Med Ctr, Chicago, IL 60637 USA. [Richards, D.] US Oncol Res, Tyler, TX USA. [Garbo, L.] New York Oncol Hematol, Albany, NY USA. [Garon, E.] Univ Calif Los Angeles, Santa Monica, CA USA. [Lima, C. Rocha] Univ Miami, Sylvester Comprehens Canc Ctr, Miami, FL USA. [Safran, H.] Rhode Isl Hosp, Providence, RI USA. [Feigal, E.] Amgen Inc, Thousand Oaks, CA 91320 USA. [Bray, S.] Amgen Ltd, Cambridge, England. [Fuchs, C.] Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD OCT PY 2010 VL 21 SU 8 BP 233 EP 234 PG 2 WC Oncology SC Oncology GA 666LE UT WOS:000283115900754 ER PT J AU Oberg, K Kulke, M Pavel, M Phan, A Hoosen, S St Peter, J Cherfi, A Yao, JC AF Oberg, K. Kulke, M. Pavel, M. Phan, A. Hoosen, S. St Peter, J. Cherfi, A. Yao, J. C. TI PROGNOSTIC AND PREDICTIVE VALUE OF CHROMOGRANIN A AND NEURON-SPECIFIC ENOLASE IN PATIENTS (PTS) WITH ADVANCED PANCREATIC NEUROENDOCRINE TUMORS (PNET) TREATED WITH EVEROLIMUS SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 35th European-Society-for-Medical-Oncology (ESMO) Congress CY OCT 08-12, 2010 CL Milan, ITALY SP European Soc Med Oncol C1 [Oberg, K.] Univ Hosp, Uppsala, Sweden. [Kulke, M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Pavel, M.] Univ Berlin, Campus Virchow Klinikum, Charite, Berlin, Germany. [Phan, A.; Yao, J. C.] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA. [Hoosen, S.; St Peter, J.] Novartis Oncol, Florham Pk, NJ USA. [Cherfi, A.] Novartis Pharma AG, Basel, Switzerland. NR 0 TC 1 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD OCT PY 2010 VL 21 SU 8 BP 266 EP 266 PG 1 WC Oncology SC Oncology GA 684YX UT WOS:000284592300056 ER PT J AU George, DJ Vogelzang, N Schellhammer, PF Higano, CS Frohlich, MW Kantoff, PW AF George, D. J. Vogelzang, N. Schellhammer, P. F. Higano, C. S. Frohlich, M. W. Kantoff, P. W. TI SURVIVAL RESULTS OF THE IMPACT TRIAL OF SIPULEUCEL-T FOR ADVANCED PROSTATE CANCER SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 35th European-Society-for-Medical-Oncology (ESMO) Congress CY OCT 08-12, 2010 CL Milan, ITALY SP European Soc Med Oncol C1 [George, D. J.] Duke Univ, Med Ctr, Dept Med & Surg, Durham, NC USA. [Vogelzang, N.] Comprehens Canc Ctr NV, Las Vegas, NV USA. [Schellhammer, P. F.] Eastern Virginia Med Sch, Norfolk, VA 23501 USA. [Higano, C. S.] Univ Washington, Sch Med, Seattle, WA USA. [Frohlich, M. W.] Dendreon Corp, Clin Affairs, Seattle, WA USA. [Kantoff, P. W.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD OCT PY 2010 VL 21 SU 8 BP 272 EP 272 PG 1 WC Oncology SC Oncology GA 684YX UT WOS:000284592300073 ER PT J AU Klotz, L Smith, MR van der Meulen, EA Tanko, LB AF Klotz, L. Smith, M. R. van der Meulen, E. A. Tanko, L. B. TI BASELINE CARDIOVASCULAR RISK FACTORS PREDICT CARDIOVASCULAR (CV) EVENTS DURING ANDROGEN DEPRIVATION THERAPY (ADT) WITH DEGARELIX SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 35th European-Society-for-Medical-Oncology (ESMO) Congress CY OCT 08-12, 2010 CL Milan, ITALY SP European Soc Med Oncol C1 [Klotz, L.] Univ Toronto, Div Urol, Toronto, ON, Canada. [Smith, M. R.] Massachusetts Gen Hosp, Boston, MA 02114 USA. [van der Meulen, E. A.] Ferring Pharmeceut AS, Clin Randd, Copenhagen S, Denmark. [Tanko, L. B.] Ferring Pharmeceut AS, Global Clin Randd, Urol, Copenhagen S, Denmark. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD OCT PY 2010 VL 21 SU 8 BP 276 EP 277 PG 2 WC Oncology SC Oncology GA 684YX UT WOS:000284592300086 ER PT J AU Hirmand, M Scher, HI Beer, T Higano, CS Taplin, M Efstathiou, E AF Hirmand, M. Scher, H. I. Beer, T. Higano, C. S. Taplin, M. Efstathiou, E. TI CIRCULATING TUMOR CELLS (CTC) AND PROSTATE-SPECIFIC ANTIGEN (PSA) AS RESPONSE INDICATOR BIOMARKERS IN CHEMOTHERAPY-NAIVE PATIENTS WITH PROGRESSIVE CASTRATION-RESISTANT PROSTATE CANCER (CRPC) TREATED WITH MDV3100 SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 35th European-Society-for-Medical-Oncology (ESMO) Congress CY OCT 08-12, 2010 CL Milan, ITALY SP European Soc Med Oncol C1 [Hirmand, M.] Medivation, Clin Dev, San Francisco, CA USA. [Scher, H. I.] Mem Sloan Kettering Canc Ctr, Genitourinary Oncol Serv, New York, NY 10021 USA. [Beer, T.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Higano, C. S.] Univ Washington, Sch Med, Seattle, WA USA. [Taplin, M.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Efstathiou, E.] Univ Texas Houston, MD Anderson Canc Ctr, Houston, TX 77030 USA. NR 0 TC 1 Z9 1 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD OCT PY 2010 VL 21 SU 8 BP 277 EP 277 PG 1 WC Oncology SC Oncology GA 684YX UT WOS:000284592300087 ER PT J AU Michaelson, D Kpamegan, EE Perez, JR Brown, J AF Michaelson, D. Kpamegan, E. E. Perez, J. Ricardo Brown, J. TI ZOLEDRONIC ACID (ZOL) REDUCES THE INCIDENCE OF SKELETAL-RELATED EVENT (SRES) AND MAY IMPROVE SURVIVAL IN PATIENTS WITH BONE METASTASES (METS) FROM RENAL CELL CARCINOMA (RCC): A RETROSPECTIVE INTEGRATED ANALYSIS SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 35th European-Society-for-Medical-Oncology (ESMO) Congress CY OCT 08-12, 2010 CL Milan, ITALY SP European Soc Med Oncol C1 [Michaelson, D.] Massachusetts Gen Hosp, Dept Hematol Oncol, Boston, MA 02114 USA. [Kpamegan, E. E.; Perez, J. Ricardo] Novartis Pharmaceut Inc, E Hanover, NJ USA. [Brown, J.] Univ Leeds, Leeds, W Yorkshire, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD OCT PY 2010 VL 21 SU 8 BP 287 EP 287 PG 1 WC Oncology SC Oncology GA 684YX UT WOS:000284592300120 ER PT J AU Cella, D Bushmakin, AG Cappelleri, JC Charbonneau, C Michaelson, MD Motzer, RJ AF Cella, D. Bushmakin, A. G. Cappelleri, J. C. Charbonneau, C. Michaelson, M. D. Motzer, R. J. TI BASELINE QUALITY OF LIFE AS A PROGNOSTIC TOOL OF MEDIAN SURVIVAL IN PATIENTS RECEIVING SUNITINIB FOR METASTATIC RENAL CELL CARCINOMA SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 35th European-Society-for-Medical-Oncology (ESMO) Congress CY OCT 08-12, 2010 CL Milan, ITALY SP European Soc Med Oncol C1 [Cella, D.] Northwestern Univ, Feinberg Sch Med, Dept Med Social Sci, Chicago, IL 60611 USA. [Bushmakin, A. G.; Cappelleri, J. C.] Pfizer Oncol, New London, CT USA. [Charbonneau, C.] Pfizer Oncol, New York, NY USA. [Michaelson, M. D.] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA. [Motzer, R. J.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD OCT PY 2010 VL 21 SU 8 BP 289 EP 290 PG 2 WC Oncology SC Oncology GA 684YX UT WOS:000284592300127 ER PT J AU Kaye, S Kaufman, B Lubinski, J Matulonis, U Gourley, C Karlan, B Taylor, D Wickens, M Carmichael, J AF Kaye, S. Kaufman, B. Lubinski, J. Matulonis, U. Gourley, C. Karlan, B. Taylor, D. Wickens, M. Carmichael, J. TI PHASE II STUDY OF THE ORAL PARP INHIBITOR OLAPARIB (AZD2281) VERSUS LIPOSOMAL DOXORUBICIN IN OVARIAN CANCER PATIENTS WITH BRCA1 AND/OR BRCA2 MUTATIONS SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 35th European-Society-for-Medical-Oncology (ESMO) Congress CY OCT 08-12, 2010 CL Milan, ITALY SP European Soc Med Oncol C1 [Kaye, S.] Royal Marsden Hosp, Dept Med Oncol, Sutton, Surrey, England. [Kaufman, B.] Chaim Sheba Med Ctr, Div Oncol, IL-52621 Tel Hashomer, Israel. [Lubinski, J.] Pomeranian Med Univ, Szczecin, Poland. [Matulonis, U.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Gourley, C.] Univ Edinburgh, Canc Res Ctr, Western Gen Hosp, Edinburgh, Midlothian, Scotland. [Karlan, B.] Cedars Sinai Med Ctr, Div Gynecol Oncol, Los Angeles, CA 90048 USA. [Taylor, D.; Wickens, M.; Carmichael, J.] AstraZeneca, Macclesfield, Cheshire, England. NR 0 TC 9 Z9 9 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD OCT PY 2010 VL 21 SU 8 BP 304 EP 304 PG 1 WC Oncology SC Oncology GA 684YX UT WOS:000284592300173 ER PT J AU Matulonis, U Sharma, SK Ghamande, S Gordon, MS Del Prete, S Ray-Coquard, I Kutarska, E Liu, H Fingert, H Schilder, RJ AF Matulonis, U. Sharma, S. K. Ghamande, S. Gordon, M. S. Del Prete, S. Ray-Coquard, I. Kutarska, E. Liu, H. Fingert, H. Schilder, R. J. TI SINGLE-AGENT ACTIVITY AND SAFETY OF THE INVESTIGATIONAL AURORA A KINASE INHIBITOR MLN8237 IN PATIENTS WITH PLATINUM-TREATED EPITHELIAL OVARIAN, FALLOPIAN TUBE, OR PRIMARY PERITONEAL CARCINOMA SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 35th European-Society-for-Medical-Oncology (ESMO) Congress CY OCT 08-12, 2010 CL Milan, ITALY SP European Soc Med Oncol C1 [Matulonis, U.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Sharma, S. K.] Hinsdale Hosp, Hinsdale, IL USA. [Ghamande, S.] Med Coll Georgia, Augusta, GA 30912 USA. [Gordon, M. S.] Pinnacle Oncol Hematol, Scottsdale, AZ USA. [Del Prete, S.] Bennett Canc Ctr, Stamford, CT USA. [Ray-Coquard, I.] Ctr Leon Berard, F-69373 Lyon, France. [Kutarska, E.] Ctr Onkol Ziemi Lubelskiej, Sect Gynecol Oncol Radiotherapy & Chemotherapy 3, Lublin, Poland. [Liu, H.] Millennium Pharmaceut Inc, Biostat, Cambridge, MA USA. [Fingert, H.] Millennium Pharmaceut Inc, Clin Dev, Cambridge, England. [Schilder, R. J.] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD OCT PY 2010 VL 21 SU 8 BP 305 EP 305 PG 1 WC Oncology SC Oncology GA 684YX UT WOS:000284592300176 ER PT J AU Posner, M Lorch, J Goloubeva, O Tan, M Schumaker, L Sarlis, N Haddad, R Cullen, KJ AF Posner, M. Lorch, J. Goloubeva, O. Tan, M. Schumaker, L. Sarlis, N. Haddad, R. Cullen, K. J. TI FIVE-YEAR SURVIVAL (OS) AND PATTERNS OF FAILURE FOR HUMAN PAPILLOMAVIRUS (HPV) POSITIVE AND NEGATIVE OROPHARYNX CANCER (OPC) IN THE TAX 324 CLINICAL TRIAL: RESULTS OF SEQUENTIAL THERAPY SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 35th European-Society-for-Medical-Oncology (ESMO) Congress CY OCT 08-12, 2010 CL Milan, ITALY SP European Soc Med Oncol C1 [Posner, M.; Lorch, J.] Dana Farber Canc Inst, HNOP, Boston, MA 02115 USA. [Goloubeva, O.; Tan, M.] Marlene & Stewart Greenebaum Canc Ctr, Baltimore, MD USA. [Schumaker, L.; Cullen, K. J.] Univ Maryland, Greenebaum Canc Ctr, Baltimore, MD 21201 USA. [Sarlis, N.] Sanofi Aventis, Oncol, Bridgewater, MA USA. [Haddad, R.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD OCT PY 2010 VL 21 SU 8 BP 314 EP 314 PG 1 WC Oncology SC Oncology GA 684YX UT WOS:000284592300206 ER PT J AU Haanen, JB Hodi, FS O'Day, SJ McDermott, DF Robert, C Schadendorf, D van den Eertwegh, AJ Chen, T Hoos, A Urba, WJ AF Haanen, J. B. Hodi, F. S. O'Day, S. J. McDermott, D. F. Robert, C. Schadendorf, D. van den Eertwegh, A. J. Chen, T. Hoos, A. Urba, W. J. TI IPILIMUMAB IMPROVES OVERALL SURVIVAL IN PATIENTS WITH PREVIOUSLY TREATED, ADVANCED MELANOMA: LONG-TERM SURVIVAL RESULTS FROM A PHASE III TRIAL SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 35th European-Society-for-Medical-Oncology (ESMO) Congress CY OCT 08-12, 2010 CL Milan, ITALY SP European Soc Med Oncol C1 [Haanen, J. B.] Antoni Van Leeuwenhoek Ziekenhuis, Nederlands Kankerinst, Amsterdam, Netherlands. [Hodi, F. S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [O'Day, S. J.] Angeles Clin & Res Inst, Santa Monica, CA USA. [McDermott, D. F.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Robert, C.] Inst Gustave Roussy, Serv Dermatol, F-94805 Villejuif, France. [Schadendorf, D.] Univ Hosp Essen, Dept Dermatol, Essen, Germany. [van den Eertwegh, A. J.] VU Univ, Med Ctr, Amsterdam, Netherlands. [Chen, T.] Columbia Univ, New York, NY USA. [Hoos, A.] Bristol Myers Squibb Co, Gcr Oncol, Wallingford, Oxon, England. [Urba, W. J.] Earle A Chiles Res Inst, Portland, OR USA. NR 0 TC 2 Z9 2 U1 2 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD OCT PY 2010 VL 21 SU 8 BP 402 EP 402 PG 1 WC Oncology SC Oncology GA 684YX UT WOS:000284592300528 ER PT J AU Robert, C Hodi, FS O'Day, SJ Peschel, C Ottensmeier, CH Trefzer, U Lorigan, P Messina, M Ibrahim, R Schadendorf, D AF Robert, C. Hodi, F. S. O'Day, S. J. Peschel, C. Ottensmeier, C. H. Trefzer, U. Lorigan, P. Messina, M. Ibrahim, R. Schadendorf, D. TI RE-INDUCTION WITH IPILIMUMAB, GP100 PEPTIDE VACCINE, OR A COMBINATION OF BOTH IN A PHASE III STUDY OF PREVIOUSLY-TREATED PATIENTS WITH ADVANCED MELANOMA: UPDATE OF CLINICAL CHARACTERISTICS OF PATIENTS SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 35th European-Society-for-Medical-Oncology (ESMO) Congress CY OCT 08-12, 2010 CL Milan, ITALY SP European Soc Med Oncol C1 [Robert, C.] Inst Gustave Roussy, Serv Dermatol, F-94805 Villejuif, France. [Hodi, F. S.] Dana Farber Canc Inst, Boston, MA 02115 USA. [O'Day, S. J.] Angeles Clin & Res Inst, Santa Monica, CA USA. [Peschel, C.] Tech Univ Munich, Klinikum Rechts Isar, Dept Med 3, D-8000 Munich, Germany. [Ottensmeier, C. H.] Southampton Gen Hosp, Southampton SO9 4XY, Hants, England. [Trefzer, U.] Charite Univ Med Berlin, Klin Fue Dermatol Venerol & Allergol, Berlin, Germany. [Lorigan, P.] Christie Hosp NHS Trust, Dept Med Oncol, Manchester M20 4BX, Lancs, England. [Messina, M.] Bristol Myers Squibb Co, Princeton, NJ USA. [Ibrahim, R.] Bristol Myers Squibb Co, Wallingford, CT 06492 USA. [Schadendorf, D.] Univ Klinikum Essen, Essen, Germany. RI Ottensmeier, Christian/E-8131-2012; Lorigan, Paul/J-6898-2015 OI Ottensmeier, Christian/0000-0003-3619-1657; Lorigan, Paul/0000-0002-8875-2164 NR 0 TC 3 Z9 3 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 OCT PY 2010 VL 21 SU 8 BP 403 EP 404 PG 2 WC Oncology SC Oncology GA 684YX UT WOS:000284592300531 ER PT J AU Schoffski, P Reichardt, P Blay, JY Dumez, H Morgan, JA Ray-Coquard, I Hollaender, N Jappe, A Demetri, GD AF Schoffski, P. Reichardt, P. Blay, J-Y Dumez, H. Morgan, J. A. Ray-Coquard, I. Hollaender, N. Jappe, A. Demetri, G. D. TI A phase I-II study of everolimus (RAD001) in combination with imatinib in patients with imatinib-resistant gastrointestinal stromal tumors SO ANNALS OF ONCOLOGY LA English DT Article DE everolimus (RAD001); gastrointestinal stromal tumors; GIST; imatinib ID ADVANCED SOLID TUMORS; MAMMALIAN TARGET; PROGNOSTIC-FACTORS; INHIBITION; RAPAMYCIN; MESYLATE; SURVIVAL; MECHANISMS; MUTATIONS; SUNITINIB AB Patients and methods: In phase I, patients received imatinib (600/800 mg/day) combined with weekly (20 mg) or daily (2.5/5.0 mg) everolimus to determine the optimal dose. In phase II, patients were divided into two strata (progression on imatinib only; progression after imatinib and sunitinib/other tyrosine kinase inhibitor) and received everolimus 2.5 mg plus imatinib 600 mg/day. Primary end point was 4-month progression-free survival (PFS). Results: Combination treatment was well tolerated. Common adverse events were diarrhea, nausea, fatigue, and anemia. In phase II strata 1 and 2, 4 of 23 (17%) and 13 of 35 (37%) assessable patients, respectively, were progression free at 4 months; median PFS was 1.9 and 3.5 months, and median overall survival was 14.9 and 10.7 months, respectively. In stratum 1, 36% had stable disease (SD) and 54% progressive disease (PD), while in stratum 2, 2% had partial response, 43% SD, and 32% PD. Conclusion: Predetermined efficacy criteria were met in both strata. The combination of everolimus and imatinib after failure on imatinib and sunitinib merits further investigation in GIST. C1 [Schoffski, P.] Catholic Univ Louvain, Expt Oncol Lab, Dept Gen Med Oncol, Univ Hosp Leuven,Leuven Canc Inst, B-3000 Louvain, Belgium. [Reichardt, P.] HELIOS Klinikum Berlin Buch, Dept Hematol & Oncol, Berlin, Germany. [Blay, J-Y; Ray-Coquard, I.] Ctr Leon Berard, Dept Oncol, F-69373 Lyon, France. [Morgan, J. A.; Demetri, G. D.] Dana Farber Canc Inst, Dept Gen Med Oncol, Boston, MA 02115 USA. [Hollaender, N.; Jappe, A.] Novartis Pharma AG, Dept Oncol, Basel, Switzerland. RP Schoffski, P (reprint author), Catholic Univ Louvain, Expt Oncol Lab, Dept Gen Med Oncol, Univ Hosp Leuven,Leuven Canc Inst, Herestr 49, B-3000 Louvain, Belgium. EM patrick.schoffski@uzleuven.be RI Blay, Jean-Yves/N-3966-2016 OI Blay, Jean-Yves/0000-0001-7190-120X FU Novartis Pharmaceuticals, Basel, Switzerland; Novartis; Daiichi-Sankyo; Infinity Pharmaceuticals; Bristol-Myers Squibb; Johnson Johnson; Ariad; Pfizer FX Novartis Pharmaceuticals, Basel, Switzerland.; Dr Schofski is a member of the speakers' bureau of Novartis and has received research funding from them. Dr Demetri has reported consultancy work and/or honoraria for Novartis, Pfizer, Ariad, Johnson and Johnson, Genentech, Infinity Pharmaceuticals, ZioPharm, Alnylam, Idera, Bayer, EMD-Serono, Amgen, Millenium/Takeda, PamGene, Plexxikon, N-of-One, and Kolltan Pharmaceuticals; his institute has received research support from Daiichi-Sankyo, Infinity Pharmaceuticals, Bristol-Myers Squibb, Johnson & Johnson, Ariad, Pfizer, and Novartis; he reports equity in Plexxikon, N-of-One, and Kolltan Pharmaceuticals. Drs Hollaender and Jappe are employees of Novartis. The other authors have not reported any conflicts of interest. NR 35 TC 50 Z9 52 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD OCT PY 2010 VL 21 IS 10 BP 1990 EP 1998 DI 10.1093/annonc/mdq076 PG 9 WC Oncology SC Oncology GA 654LA UT WOS:000282168600009 PM 20507881 ER PT J AU Pandurengan, RK Dumont, AG Araujo, DM Ludwig, JA Ravi, V Patel, S Garber, J Benjamin, RS Strom, SS Trent, JC AF Pandurengan, R. K. Dumont, A. G. Araujo, D. M. Ludwig, J. A. Ravi, V. Patel, S. Garber, J. Benjamin, R. S. Strom, S. S. Trent, J. C. TI Survival of patients with multiple primary malignancies: a study of 783 patients with gastrointestinal stromal tumor SO ANNALS OF ONCOLOGY LA English DT Article DE GIST; imatinib; predisposition; risk; synchronous ID EXTRA-ADRENAL PARAGANGLIOMA; PULMONARY CHONDROMA; DOSE IMATINIB; LEIOMYOSARCOMA; PREVALENCE; MESYLATE; TRIAL AB Background: We sought to investigate the characteristics and survival rate of patients with gastrointestinal stromal tumor (GIST) associated with other primary malignancies. Patients and methods: A total of 783 patients with GIST were identified from 1995 to 2007. Additional primaries included tumors not considered metastasis, invasion, or recurrence of GIST, nor non-melanoma skin cancer. Data on gender, age at diagnosis, follow-up time after diagnosis, and death were collected. Results: Of the 783 patients with GIST, 153(20%) were identified with at least one additional primary. Patients with additional primaries were more often men (M : F 1.5 versus 1.3) and older (66 versus 53 years). More patients had another cancer diagnosed before (134) than after (52) GIST. Primaries observed before GIST were cancers of the prostate (25), breast (12), esophagus (9), and kidney (7) and melanoma (6). Lung (5) and kidney (5) primaries were the most frequent after GIST. The 5-year survival was 68% for patients with primaries before GIST, 61% for patients with primaries after GIST, 58% for patients with GIST only, and 49% for patients with two or more primaries in addition to GIST (P = 0.002). Conclusions: Approximately 20% of patients with GIST develop other cancers. Inferior median 5-year survival was observed in patients with GIST with two or more other cancers. The etiology and clinical implications of other malignancies in patients with GIST should be investigated. C1 [Dumont, A. G.; Araujo, D. M.; Ludwig, J. A.; Ravi, V.; Patel, S.; Benjamin, R. S.; Trent, J. C.] Univ Texas MD Anderson Canc Ctr, Dept Sarcoma Med Oncol, Houston, TX 77030 USA. [Pandurengan, R. K.; Strom, S. S.] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. [Dumont, A. G.; Ludwig, J. A.; Trent, J. C.] Univ Texas MD Anderson Canc Ctr, Adult Sarcoma Res Ctr, Houston, TX 77030 USA. [Garber, J.] Dana Farber Canc Inst, Canc Risk & Prevent Program, Boston, MA 02115 USA. RP Trent, JC (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Sarcoma Med Oncol, 8515 Fannin St,Suite NAO1-041A, Houston, TX 77030 USA. EM jtrent@mdanderson.org FU Institutional Physician-Scientist award; National Institutes of Health/National Caner Institute [1K23CA109060-05]; Amschwand Sarcoma Cancer Foundation FX Institutional Physician-Scientist award to JCT; National Institutes of Health/National Caner Institute grant (1K23CA109060-05) to JCT; Amschwand Sarcoma Cancer Foundation to JCT. NR 18 TC 36 Z9 38 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD OCT PY 2010 VL 21 IS 10 BP 2107 EP 2111 DI 10.1093/annonc/mdq078 PG 5 WC Oncology SC Oncology GA 654LA UT WOS:000282168600026 PM 20348145 ER PT J AU Burns, JA Lopez-Guerra, G Heaton, JT Kobler, JB Kraas, J Zeitels, SM AF Burns, James A. Lopez-Guerra, Gerardo Heaton, James T. Kobler, James B. Kraas, Julie Zeitels, Steven M. TI Cooling the "Oven": A Temperature Study of Air and Glottal Tissue During Laser Surgery in an Ex Vivo Calf Larynx Model SO ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY LA English DT Article DE cooling; laser; microlaryngoscopy; thermal damage; vocal cord; vocal fold ID CARBON-DIOXIDE LASER; CHORIOALLANTOIC MEMBRANE; CLINICAL EXPERIENCE; THULIUM LASER; SOFT-TISSUE; YAG LASER; CO2-LASER; PAPILLOMATOSIS; TRACHEA; LESIONS AB Objectives: Endoscopic microlaryngeal laser surgery performed with general anesthesia through a laryngoscope speculum generates heat that accumulates at the distal lumen, creating an "oven" effect and potentially causing bystander thermal damage to nontarget tissue such as the contralateral vocal fold. We report the effects of cooling on air and tissue temperatures that occurred during simulated laryngeal laser surgery with KTP and thulium lasers in an ex vivo calf model. Methods: Ten fresh excised calf larynges were studied at room temperature. Laser energy was applied to one vocal fold for 2 minutes, with or without cooling, while temperatures were monitored with sensors placed within the glottal lumen or inserted superficially into the contralateral vocal fold. A pulsed KTP laser (525 mJ) was used for 5 larynges, and a thulium laser (7 W, continuous) was used for the other 5 larynges. Results: Heating was slightly greater for the KTP laser than for the thulium laser with use of these parameters. The lumen temperatures for both lasers increased an average of 13.2 degrees C without cooling, but only 6.7 degrees C with cooling (p < 0.05). The contralateral vocal fold (subepithelial space) temperature increased an average of 6.8 degrees C without cooling, but only 4.2 degrees C with cooling (p > 0.05). Conclusions: Cooling with room-temperature air during laryngeal laser surgery reduces luminal air and contralateral vocal fold temperatures. This effect is believed to be due to elimination of the plume of steam and smoke that significantly heats surrounding structures. C1 [Burns, James A.] Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Surg, Boston, MA 02115 USA. RP Burns, JA (reprint author), Massachusetts Gen Hosp, Ctr Laryngeal Surg & Voice Rehabil, 1 Bowdoin Sq,11th Floor, Boston, MA 02114 USA. FU Institute of Laryngology and Voice Restoration; Eugene B. Casey Foundation FX From the Department of Surgery, Harvard Medical School, and the Center for Laryngeal Surgery and Voice Rehabilitation, Massachusetts General Hospital, Boston, Massachusetts. This work was supported in part by the Institute of Laryngology and Voice Restoration and the Eugene B. Casey Foundation. Dr Zeitels has an equity interest in Endocraft LLC, which makes the glottiscope that was used in the study. NR 21 TC 2 Z9 2 U1 0 U2 0 PU ANNALS PUBL CO PI ST LOUIS PA 4507 LACLEDE AVE, ST LOUIS, MO 63108 USA SN 0003-4894 J9 ANN OTO RHINOL LARYN JI Ann. Otol. Rhinol. Laryngol. PD OCT PY 2010 VL 119 IS 10 BP 684 EP 689 PG 6 WC Otorhinolaryngology SC Otorhinolaryngology GA 662YI UT WOS:000282849800007 PM 21049854 ER PT J AU Conrad, MF Ergul, EA Patel, VI Paruchuri, V Kwolek, CJ Cambria, RP AF Conrad, Mark F. Ergul, Emel A. Patel, Virendra I. Paruchuri, Vikram Kwolek, Christopher J. Cambria, Richard P. TI Management of Diseases of the Descending Thoracic Aorta in the Endovascular Era A Medicare Population Study SO ANNALS OF SURGERY LA English DT Article; Proceedings Paper CT 130th Annual Meeting of the American-Surgical-Association CY APR 08-10, 2010 CL Chicago, IL SP Amer Surg Assoc ID CONTROLLED CLINICAL-TRIAL; OPEN SURGICAL REPAIR; STENT GRAFT REPAIR; ANEURYSM REPAIR; COST-EFFECTIVENESS; DISSECTION; EXPERIENCE; MORTALITY; PARAPLEGIA; METAANALYSIS AB Objective: Prospective trials have shown improved perioperative outcomes with endovascular repair of thoracic aortic (TEVAR) pathologies compared with conventional surgery (OPEN). There are no long-term population data detailing the impact of TEVAR on practice patterns and results of treatment of descending thoracic aortic pathology (DTA), which are the goal of this study. Methods: All procedures performed on the DTA captured in the Medicare database from 2004 to 2007 were identified by ICD-9 codes and stratified into OPEN and TEVAR cohorts. Outcomes included perioperative mortality (chi(2)) and 5-year actuarial survival. Results: There were 11,166 patients identified (4838 [43%] TEVAR vs. 6328 [57%] OPEN) with 7247 (65%) nonruptured, degenerative thoracic aortic aneurysms (TAA), 2701 (24%) descending aortic dissections, 1033 (9%) thoracic aortic ruptures, and 185 (2%) traumatic aortic tears. The distribution of cases changed significantly during the study period (P < 0.0001) with an increase in TEVAR, decrease in OPEN, and increase in total cases over time (Table 1). The perioperative mortality was lower in the TEVAR group for the entire population (360 [7.4%] TEVAR vs. 1175 [18.5%] OPEN, P < 0.0001), and for the individual pathologies: TAA (182/3529 [5%] TEVAR vs. 451/3718 [12%] OPEN, P < 0.001), dissections (76/833 [9%] TEVAR vs. 399/1868 [21%] OPEN, P < 0.001) and ruptures (87/368 [24%] TEVAR vs. 298/665 [45%] OPEN, P < 0.0001). The Kaplan-Meier curve significantly favored TEVAR for the entire cohort because of the early mortality of the OPEN cohort but the curves converged by 5 years. The 5-year survival by indication was: entire population (53.4% TEVAR vs. 53.3% OPEN, P < 0.0001), TAA (55.8% TEVAR vs. 59.7% OPEN, P = 0.84), dissection (58.2% TEVAR vs. 50.6% OPEN, P < 0.0001), ruptures (23.3% TEVAR vs. 25.3% OPEN, P < 0.001), and trauma (62.9% TEVAR vs. 50.9% OPEN, P = 0.12). Conclusion: There has been a significant increase in the use of TEVAR for management of diseases of the DTA. TEVAR offers a significant perioperative survival advantage when compared with OPEN regardless of the indication for repair. However, in the Medicare population, the 5-year survival is similar between the 2 cohorts. C1 Massachusetts Gen Hosp, Gen Surg Serv, Div Vasc & Endovasc Surg, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA USA. RP Conrad, MF (reprint author), 15 Parkman St,WAC 440, Boston, MA 02114 USA. EM mconrad@partners.org NR 43 TC 47 Z9 49 U1 0 U2 1 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 OCT PY 2010 VL 252 IS 4 BP 603 EP 609 DI 10.1097/SLA.0b013e3181f4eaef PG 7 WC Surgery SC Surgery GA 656VO UT WOS:000282369400005 PM 20881766 ER PT J AU Raval, MV Bentrem, DJ Stewart, AK Ko, CY Reynolds, M AF Raval, Mehul V. Bentrem, David J. Stewart, Andrew K. Ko, Clifford Y. Reynolds, Marleta TI Utilization of Total Thyroidectomy for Differentiated Thyroid Cancer in Children SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article ID TERM-FOLLOW-UP; DATA-BASE; UNITED-STATES; YOUNG-ADULTS; CARCINOMA; DISEASE; ADOLESCENTS; RECURRENCE; MANAGEMENT; CHILDHOOD AB Purpose. Recent recommendations suggest that total thyroidectomy (TT) is the surgical management of choice for differentiated thyroid cancer in children. The objective of this study is to assess trends in extent of surgical resection for differentiated thyroid cancer in children over the past two decades and to identify patient, tumor or hospital factors associated with use of TT. Patients and Methods. Of 8,013 patients (aged 0-21 years) with differentiated thyroid cancer from the National Cancer Data Base (1985-2007), 5,933(74%) underwent TT. Trends in extent of surgery were examined. Logistic regression was used to identify factors that predict use of TT. Results. Use of TT increased from 50.6% in 1985 to 84% in 2007 (P < 0.001). Patients were more likely to undergo TT if they had higher household income or had private insurance (P = 0.002 and P = 0.037). Patients were more likely to undergo TT if they had larger tumors or if there were nodal metastases present at time of resection (both P < 0.001). After adjusting for patient and tumor factors, patients treated at high-volume or Children's Oncology Group hospitals were more likely to undergo TT than patients treated at low-volume or non-Children's Oncology Group hospitals (P < 0.001). Conclusions. Overall utilization of TT in children with differentiated thyroid cancer has steadily increased over the past 23 years in the USA. Variations in use of TT are not only related to tumor factors including size and nodal involvement, but also are also related to socioeconomic and hospital factors, demonstrating disparities in care. C1 [Raval, Mehul V.; Stewart, Andrew K.; Ko, Clifford Y.] Amer Coll Surg, Div Res & Optimal Patient Care, Canc Programs, Chicago, IL USA. [Raval, Mehul V.; Reynolds, Marleta] Childrens Mem Hosp, Div Pediat Surg, Chicago, IL 60614 USA. [Raval, Mehul V.; Bentrem, David J.] Northwestern Univ, Div Gastrointestinal & Oncol Surg, Dept Surg, Feinberg Sch Med, Chicago, IL 60611 USA. [Bentrem, David J.] Jesse Brown VA Med Ctr, Chicago, IL USA. [Ko, Clifford Y.] Univ Calif Los Angeles, Dept Surg, Los Angeles, CA 90024 USA. [Ko, Clifford Y.] VA Greater Los Angeles Healthcare Syst, Los Angeles, CA USA. RP Raval, MV (reprint author), Amer Coll Surg, Div Res & Optimal Patient Care, Canc Programs, Chicago, IL USA. EM mehulvraval@gmail.com OI Raval, Mehul/0000-0002-1527-2661 FU John Gray Research Fellowship; Daniel F. and Ada L. Rice Foundation; Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service; American College of Surgeons Commission on Cancer; American Cancer Society FX M.V.R. participates in the American College of Surgeons Clinical Scholars in Residence Program. M.V.R. is supported by the John Gray Research Fellowship and the Daniel F. and Ada L. Rice Foundation. D.J.B. is supported by a career development award from the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development Service. The National Cancer Data Base is supported by the American College of Surgeons, Commission on Cancer, and the American Cancer Society. NR 53 TC 10 Z9 11 U1 0 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD OCT PY 2010 VL 17 IS 10 BP 2545 EP 2553 DI 10.1245/s10434-010-1083-3 PG 9 WC Oncology; Surgery SC Oncology; Surgery GA 669ZP UT WOS:000283389200003 PM 20429037 ER PT J AU Jacobs, JP Edwards, FH Shahian, DM Haan, CK Puskas, JD Morales, DLS Gammie, JS Sanchez, JA Brennan, M O'Brien, SM Dokholyan, RS Hammill, BG Curtis, LH Peterson, ED Badhwar, V George, KM Mayer, JE Chitwood, R Murray, GF Grover, FL AF Jacobs, Jeffrey Phillip Edwards, Fred H. Shahian, David M. Haan, Constance K. Puskas, John D. Morales, David L. S. Gammie, James S. Sanchez, Juan A. Brennan, Matthew O'Brien, Sean M. Dokholyan, Rachel S. Hammill, Bradley G. Curtis, Lesley H. Peterson, Eric D. Badhwar, Vinay George, Kristopher M. Mayer, John E., Jr. Chitwood, Randolph, Jr. Murray, Gordon F. Grover, Frederick L. TI Successful Linking of The Society of Thoracic Surgeons Adult Cardiac Surgery Database to Centers for Medicare and Medicaid Services Medicare Data SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT 46th Annual Meeting of the Society-of-Thoracic-Surgeons CY JAN 25-27, 2010 CL Ft Lauderdale, FL SP Soc Thorac Surg AB Background. The Centers for Medicare and Medicaid Services (CMS) Medicare database complements The Society of Thoracic Surgeons (STS) database by providing information about long-term outcomes and cost. This study demonstrates the feasibility of linking STS data to CMS data and examines the penetration, completeness, and representativeness of the STS database. Methods. Using variables common to both STS and CMS databases, STS operations were linked to CMS data for all CMS coronary artery bypass graft surgery (CABG) hospitalizations discharged between 2000 and 2007, inclusive. For each CMS CABG hospitalization, it was determined whether a matching STS record existed. Results. Center-level penetration (number of CMS sites with at least one matched STS participant divided by the total number of CMS CABG sites) increased from 45% to 78%. In 2007, 854 of 1,101 CMS CABG sites (78%) were linked to an STS site. Patient-level penetration number of CMS CABG hospitalizations done at STS sites divided by the total number of CMS CABG hospitalizations) increased from 51% to 84%. In 2007, 94,409 of 111,967 CMS CABG hospitalizations (84%) were at an STS site. Completeness of case inclusion at STS sites (number of CMS CABG cases at STS sites linked to STS records divided by the total number of CMS CABG cases at STS sites) increased from 88% to 97%. In 2007, 88,857 of 91,363 CMS CABG hospitalizations at STS sites (97%) were linked to an STS record. Conclusions. The successful linking of STS and CMS databases demonstrates high and increasing penetration and completeness of the STS database. Linking STS and CMS data will facilitate studying long-term outcomes of cardiothoracic surgery. (Ann Thorac Surg 2010;90:1150- 7) (c) 2010 by The Society of Thoracic Surgeons C1 [Jacobs, Jeffrey Phillip] Univ S Florida, Coll Med, Cardiac Surg Associates Florida, CHIF,All Childrens Hosp, St Petersburg, FL 33701 USA. Univ S Florida, Coll Med, Cardiac Surg Associates Florida, Childrens Hosp Tampa, St Petersburg, FL 33701 USA. Univ S Florida, Coll Med, Cardiac Surg Associates Florida, CHIF,All Childrens Hosp, Tampa, FL USA. Univ S Florida, Coll Med, Cardiac Surg Associates Florida, Childrens Hosp Tampa, Tampa, FL USA. Univ Florida, Coll Med Jacksonville, Shands Jacksonville, Jacksonville, FL USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. Emory Univ, Hosp Midtown, Atlanta, GA 30322 USA. Texas Childrens Hosp, Baylor Coll Med, Houston, TX 77030 USA. Univ Maryland, Med Ctr, Baltimore, MD 21201 USA. St Marys Hosp, Waterbury, CT USA. Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA. Cardiac Surg Associates Florida, Orlando, FL USA. Harvard Univ, Sch Med, Childrens Hosp Boston, Boston, MA USA. E Carolina Univ, Brody Sch Med, Greenville, NC USA. W Virginia Univ, Morgantown, WV 26506 USA. Univ Colorado Denver, Sch Med, Aurora, CO USA. RP Jacobs, JP (reprint author), Univ S Florida, Coll Med, Cardiac Surg Associates Florida, CHIF,All Childrens Hosp, 625 6th Ave S,Ste 475, St Petersburg, FL 33701 USA. EM jeffjacobs@msn.com RI O'Brien, Sean/H-6268-2013; Sanchez, Juan/I-1936-2016 OI Sanchez, Juan/0000-0002-6789-3208 NR 8 TC 65 Z9 65 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD OCT PY 2010 VL 90 IS 4 BP 1150 EP 1156 DI 10.1016/j.athoracsur.2010.05.042 PG 7 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 654CE UT WOS:000282145000016 PM 20868806 ER PT J AU Ge, PS Ishaque, BM Bonilla, J de Virgilio, C AF Ge, Phillip S. Ishaque, Brandon M. Bonilla, Janet de Virgilio, Christian TI Popliteal Artery Pseudoaneurysm After Isolated Hyperextension of the Knee SO ANNALS OF VASCULAR SURGERY LA English DT Article ID VASCULAR INJURIES; ARTERIOGRAPHY ALWAYS; DISLOCATIONS; REPAIR AB We report an unusual case of a traumatic pseudoaneurysm of the popliteal artery after an isolated blunt hyperextension injury to the knee. A 56-year-old man presented with a 1-month history of left knee pain that occurred after a fall onto his buttocks with hyperextension of the knee while transferring a relative out of a wheelchair. A large pulsatile mass in the posterior aspect of the left knee was palpated on physical examination, although he had warm distal extremities and 2+ distal pulses bilaterally. Magnetic resonance angiography revealed a 7.6 x 6.2 x 4.9 cm left popliteral artery pseudoaneurysm, which was subsequently treated with aneurysm exclusion with end to end reverse saphenous vein graft bypass. The development of a popliteal artery pseudoaneurysm after blunt knee injury without dislocation, fracture, or ligament injury is extremely unusual, but requires prompt treatment to avoid the potential complications of permanent functional impairment and limb loss. C1 [Ge, Phillip S.; Ishaque, Brandon M.; Bonilla, Janet] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA. [de Virgilio, Christian] W Los Angeles VA Med Ctr, Dept Surg, Los Angeles, CA USA. RP de Virgilio, C (reprint author), Harbor UCLA Med Ctr, Dept Surg, 1000 W Carson St, Torrance, CA 90309 USA. EM cdevirgilio@labiomed.org NR 22 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 0890-5096 J9 ANN VASC SURG JI Ann. Vasc. Surg. PD OCT PY 2010 VL 24 IS 7 AR 950.e7 DI 10.1016/j.avsg.2010.01.014 PG 5 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 647YC UT WOS:000281655700018 PM 20471789 ER PT J AU Weiner, M Peloquin, C Burman, W Luo, CC Engle, M Prihoda, TJ Mac Kenzie, WR Bliven-Sizemore, E Johnson, JL Vernon, A AF Weiner, Marc Peloquin, Charles Burman, William Luo, Chi-Cheng Engle, Melissa Prihoda, Thomas J. Mac Kenzie, William R. Bliven-Sizemore, Erin Johnson, John L. Vernon, Andrew TI Effects of Tuberculosis, Race, and Human Gene SLCO1B1 Polymorphisms on Rifampin Concentrations SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID PULMONARY TUBERCULOSIS; ANTIMYCOBACTERIAL DRUGS; PHARMACOKINETICS; RIFABUTIN; BIOAVAILABILITY; MOXIFLOXACIN; RESISTANCE; REGIMENS; ATORVASTATIN; RIFAPENTINE AB Rifampin has concentration-dependent activity against Mycobacterium tuberculosis. However, marked intersubject variation of rifampin concentrations occurs. In this study, we evaluated rifampin pharmacokinetics in relation to tuberculosis, geographic region, race, and single nucleotide polymorphisms of the human transporter genes SLCO1B1, SLCO1B3, and MDR1. Seventy-two adults with pulmonary tuberculosis from Africa, North America, and Spain were evaluated during multidrug intensive-phase therapy, and their results were compared to those from 16 healthy controls from North America. Rifampin pharmacokinetic values were similar between tuberculosis patients and controls (geometric mean [GM] area under the concentration-time curve from 0 to 24 h [AUC(0-24)] of 40.2 versus 40.9 mu g . h/ml; P = 0.9). However, in multivariable analyses, the rifampin AUC(0-24) was significantly affected by rifampin dosage (in mg/kg of body weight), polymorphisms in the SLCO1B1 gene, and the presence of tuberculosis by geographic region. The adjusted rifampin AUC(0-24) was lowest in patients with tuberculosis from Africa compared to that in non-African patients or control subjects. The adjusted rifampin AUC(0-24) was also 36% lower among participants with SLCO1B1 genotype c.463CA than that among participants with SLCO1B1 genotype c.463CC (adjusted GM, 29.8 versus 46.7 mu g . h/ml; P = 0.001). Polymorphisms in the SLCO1B1 gene associated with lower rifampin exposure were more frequent among black subjects. In conclusion, marked intersubject variation of the rifampin AUC(0-24) values was observed, but the mean values of the AUC(0-24) did not significantly vary between patients with tuberculosis and healthy controls. Lower rifampin exposure was associated with the polymorphism of the SLCO1B1 c. 463C>A gene. When adjusted for the patient mg/kg dosage and transporter gene polymorphisms, rifampin exposure was lower in patients with tuberculosis, which suggests that additional absorption or metabolic processes affect rifampin exposure with tuberculosis disease. C1 [Weiner, Marc] S Texas Vet Hlth Care Syst, Div Infect Dis 111, San Antonio, TX 78229 USA. [Weiner, Marc; Engle, Melissa; Prihoda, Thomas J.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA. [Peloquin, Charles] Univ Florida, Coll Pharm, Gainesville, FL 32610 USA. [Burman, William] Denver Publ Hlth, Denver, CO 80204 USA. [Luo, Chi-Cheng; Mac Kenzie, William R.; Bliven-Sizemore, Erin; Vernon, Andrew] Ctr Dis Control & Prevent, Div TB Eliminat, Atlanta, GA 30333 USA. [Johnson, John L.] Uganda Case Western Reserve Univ Res Collaborat, Case Western Reserve Univ, Dept Med, Cleveland, OH 44106 USA. RP Weiner, M (reprint author), S Texas Vet Hlth Care Syst, Div Infect Dis 111, 7400 Merton Minter Blvd, San Antonio, TX 78229 USA. EM weiner@uthscsa.edu RI Mac Kenzie, William /F-1528-2013 OI Mac Kenzie, William /0000-0001-7723-0339 FU Centers for Disease Control and Prevention; Global Alliance for TB Drug Development; Veterans Administration; NIH [MO1-RR-01346]; Tuberculosis Trials Consortium FX This work was supported by the Centers for Disease Control and Prevention, the Global Alliance for TB Drug Development, and the Veterans Administration. Assistance in evaluation of patients was provided by the Frederic C. Bartter General Clinical Research Center at the VAMC San Antonio (supported by NIH grant MO1-RR-01346). This study was sponsored by the Tuberculosis Trials Consortium. NR 33 TC 51 Z9 54 U1 2 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD OCT PY 2010 VL 54 IS 10 BP 4192 EP 4200 DI 10.1128/AAC.00353-10 PG 9 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 651EI UT WOS:000281907200021 PM 20660695 ER PT J AU Yavagal, DR Geng, DQ Akar, S Buonanno, F Kesari, S AF Yavagal, Dileep R. Geng, Deqing Akar, Serra Buonanno, Ferdinando Kesari, Santosh TI Superficial Siderosis of the Central Nervous System Due to Bilateral Jugular Vein Thrombosis SO ARCHIVES OF NEUROLOGY LA English DT Article ID OF-THE-LITERATURE; PSEUDOTUMOR CEREBRI; SURGERY AB Objective: To describe a novel cause of meningeal siderosis due to intermittent subarachnoid bleeding caused by chronic bilateral jugular vein thrombosis. Design: Case report and review of literature. Patient: A 51-year-old man with a distant history of cervical injury who presented with transient aphasia in the setting of progressive cognitive decline. Intervention: Neurological examination, magnetic resonance imaging, lumbar puncture, and angiogram. Results: The patient had intermittent subarachnoid bleeding resulting from extensive venous collaterals in the neck and cervical spine due to chronic bilateral jugular vein thrombosis. Conclusion: Unexplained neurological deterioration and history of cervical trauma warrants diagnostic consideration of superficial siderosis and jugular vein thrombosis. C1 [Kesari, Santosh] Univ Calif San Diego, Dept Neurosci, Rebecca & John Moores UCSD Canc Ctr, La Jolla, CA 92093 USA. [Buonanno, Ferdinando] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. [Akar, Serra] Hacettepe Univ, Sch Med, Ankara, Turkey. [Yavagal, Dileep R.] Univ Miami, Miller Sch Med, Dept Neurol, Miami, FL 33136 USA. [Geng, Deqing] Xuzhou Med Univ, Affiliated Hosp, Xuzhou, Jiangsu, Peoples R China. RP Kesari, S (reprint author), Moores UCSD Canc Ctr, 3855 Hlth Sci Dr, La Jolla, CA 92093 USA. EM skesari@ucsd.edu RI Kesari, Santosh/E-8461-2013 NR 14 TC 2 Z9 2 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0003-9942 EI 1538-3687 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD OCT PY 2010 VL 67 IS 10 BP 1269 EP 1271 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 661XJ UT WOS:000282766300016 PM 20937957 ER PT J AU Morse, AR Massof, RW Cole, RG Mogk, LG O'Hearn, AM Hsu, YP Faye, EE Wainapel, SF Jackson, ML AF Morse, Alan R. Massof, Robert W. Cole, Roy G. Mogk, Lylas G. O'Hearn, Annemarie M. Hsu, Yu-Pin Faye, Eleanor E. Wainapel, Stanley F. Jackson, Mary Lou TI Medicare Coverage for Vision Assistive Equipment SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; VISUAL IMPAIRMENT; UNITED-STATES; OCCUPATIONAL-THERAPY; SELF-MANAGEMENT; VETERANS-AFFAIRS; BRAIN-INJURY; OLDER-ADULTS; REHABILITATION; PREVALENCE C1 [Morse, Alan R.; Cole, Roy G.] Jewish Guild Blind, New York, NY 10023 USA. [Hsu, Yu-Pin] New York Presbyterian Hosp, Dept Rehabil Med, New York, NY USA. [Morse, Alan R.; Cole, Roy G.] Columbia Univ Coll Phys & Surg, Dept Ophthalmol, New York, NY 10032 USA. [Faye, Eleanor E.] Lighthouse Int, New York, NY USA. [Wainapel, Stanley F.] Montefiore Med Ctr, Dept Phys Med, Bronx, NY 10467 USA. [Wainapel, Stanley F.] Montefiore Med Ctr, Dept Rehabil, Bronx, NY 10467 USA. [Wainapel, Stanley F.] Albert Einstein Coll Med, Bronx, NY 10467 USA. [Massof, Robert W.] Johns Hopkins Univ, Sch Med, Wilmer Ophthalmol Inst, Lions Vis Res & Rehabil Ctr, Baltimore, MD 21205 USA. [Mogk, Lylas G.] Henry Ford Hlth Syst, Ctr Vis Rehabil & Res, Dept Ophthalmol, Detroit, MI USA. [Jackson, Mary Lou] Massachusetts Eye & Ear Infirm, Vis Rehabil Serv, Boston, MA 02114 USA. RP Morse, AR (reprint author), Jewish Guild Blind, 15 W 65th St, New York, NY 10023 USA. EM armorse@jgb.org NR 62 TC 5 Z9 5 U1 2 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD OCT PY 2010 VL 128 IS 10 BP 1350 EP 1357 PG 8 WC Ophthalmology SC Ophthalmology GA 662WC UT WOS:000282844000015 PM 20938006 ER PT J AU Batista, LM Prevedello, DM Gardner, P Carrau, RL Snyderman, CH Kassam, AB AF Batista, Leonardo M. Prevedello, Daniel M. Gardner, Paul Carrau, Ricardo L. Snyderman, Carl H. Kassam, Amin B. TI Midbrain hemorrhage mimicking pituitary apoplexy in patient using anticoagulation therapy SO ARQUIVOS DE NEURO-PSIQUIATRIA LA English DT Letter ID ATRIAL-FIBRILLATION; INTRACEREBRAL HEMORRHAGE; TUMOR C1 [Prevedello, Daniel M.; Gardner, Paul; Carrau, Ricardo L.; Snyderman, Carl H.] Univ Pittsburgh, Dept Neurol Surg, Sch Med, Pittsburgh, PA 15206 USA. [Batista, Leonardo M.] Massachusetts Gen Hosp, Dept Neurol, J Philip Kistler Stroke Res Ctr, Boston, MA 02114 USA. [Carrau, Ricardo L.; Snyderman, Carl H.] Univ Pittsburgh, Dept Otolaryngol, Sch Med, Pittsburgh, PA 15206 USA. [Kassam, Amin B.] St Johns Hlth Ctr, John Wayne Canc Inst, Chan Soon Shiong Neurosci Inst, Santa Monica, CA USA. RP Prevedello, DM (reprint author), Univ Pittsburgh, Dept Neurol Surg, Sch Med, 200 Lothrop St,Suite B400, Pittsburgh, PA 15206 USA. EM dprevedello@gmail.com NR 10 TC 0 Z9 0 U1 0 U2 1 PU ASSOC ARQUIVOS NEURO- PSIQUIATRIA PI SAO PAULO SP PA PR AMADEU AMARAL 47/33, 01327-010 SAO PAULO SP, BRAZIL SN 0004-282X J9 ARQ NEURO-PSIQUIAT JI Arq. Neuro-Psiquiatr. PD OCT PY 2010 VL 68 IS 5 BP 813 EP 815 DI 10.1590/S0004-282X2010000500028 PG 3 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 668MP UT WOS:000283274400028 PM 21049201 ER PT J AU Chang, K Francis, SA Aikawa, E Figueiredo, JL Kohler, RH McCarthy, JR Weissleder, R Plutzky, J Jaffer, FA AF Chang, Kiyuk Francis, Sanjeev A. Aikawa, Elena Figueiredo, Jose-Luiz Kohler, Rainer H. McCarthy, Jason R. Weissleder, Ralph Plutzky, Jorge Jaffer, Farouc A. TI Pioglitazone Suppresses Inflammation In Vivo in Murine Carotid Atherosclerosis Novel Detection by Dual-Target Fluorescence Molecular Imaging SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE atherosclerosis; pioglitazone; inflammation; molecular imaging; fluorescence ID ACTIVATED RECEPTOR-GAMMA; MATRIX-METALLOPROTEINASE ACTIVITY; C-REACTIVE PROTEIN; VASCULAR INFLAMMATION; ENDOTHELIAL-CELLS; DEFICIENT MICE; PPAR-GAMMA; MACROPHAGE; EXPRESSION; APOPTOSIS AB Objective-To investigate the effects of pioglitazone (PIO), a peroxisome proliferator-activated receptor gamma agonist, on plaque matrix metalloproteinase (MMP) and macrophage (Mac) responses in vivo in a molecular imaging study. Methods and Results-In vitro, PIO suppressed MMP-9 protein expression in murine peritoneal Macs (P < 0.05). To assess PIO's effects on plaque inflammation, nondiabetic apolipoprotein E(-/-) mice receiving a high-cholesterol diet (HCD) were administered an MMP-activatable fluorescence imaging agent and a spectrally distinct Mac-avid fluorescent nanoparticle. After 24 hours, mice underwent survival dual-target intravital fluorescence microscopy of carotid arterial plaques. These mice were then randomized to HCD or HCD plus 0.012% PIO for 8 weeks, followed by a second intravital fluorescence microscopy study of the same carotid plaque. In the HCD group, in vivo MMP and Mac target-to-background ratios increased similarly (P < 0.01 versus baseline). In contrast, PIO reduced MMP and Mac target-to-background ratios (P < 0.01) versus HCD. Changes in MMP and Mac signals correlated strongly (r >= 0.75). Microscopy demonstrated MMP and Mac reductions in PIO-treated mice and a PIO-modulated increase in plaque collagen. Conclusion-Serial optical molecular imaging demonstrates that plaque MMP and Mac activity in vivo intensify with hypercholesterolemia and are reduced by PIO therapy. (Arterioscler Thromb Vasc Biol. 2010;30:1933-1939.) C1 [Chang, Kiyuk; Jaffer, Farouc A.] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Chang, Kiyuk; Jaffer, Farouc A.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Aikawa, Elena; Figueiredo, Jose-Luiz; Kohler, Rainer H.; McCarthy, Jason R.; Weissleder, Ralph; Jaffer, Farouc A.] Massachusetts Gen Hosp, Ctr Mol Imaging Res, Boston, MA 02114 USA. [Figueiredo, Jose-Luiz; Kohler, Rainer H.; McCarthy, Jason R.; Weissleder, Ralph] Massachusetts Gen Hosp, Ctr Syst Biol, Boston, MA 02114 USA. [Aikawa, Elena; Weissleder, Ralph; Plutzky, Jorge; Jaffer, Farouc A.] Harvard Univ, Sch Med, Donald W Reynolds Cardiovasc Clin Res Ctr, Boston, MA USA. RP Jaffer, FA (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Simches Res Bldg,185 Cambridge St,Room 3206, Boston, MA 02114 USA. EM fjaffer@mgh.harvard.edu OI Jaffer, Farouc/0000-0001-7980-384X FU Howard Hughes Medical Institute; American Heart Association [0830352N]; Donald W. Reynolds Foundation; National Institutes of Health (NIH) [UO1 HL080731, PO1 HL 048743, T32 HL007604] FX This study was supported by a Howard Hughes Medical Institute Career Development Award (Dr Jaffer); Scientist Development Grant 0830352N from the American Heart Association (Dr Jaffer); the Donald W. Reynolds Foundation (Drs Aikawa, Weissleder, Plutzky, and Jaffer); grants UO1 HL080731 (Drs McCarthy, Weissleder, and Jaffer), PO1 HL 048743 (Dr. Plutzky) from the National Institutes of Health (NIH). Dr Francis acknowledges support from NIH T32 HL007604. NR 38 TC 33 Z9 38 U1 1 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD OCT PY 2010 VL 30 IS 10 BP 1933 EP U150 DI 10.1161/ATVBAHA.110.206342 PG 18 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 650VV UT WOS:000281882800011 PM 20689078 ER PT J AU De Meyer, SF Schwarz, T Deckmyn, H Denis, CV Nieswandt, B Stoll, G Vanhoorelbeke, K Kleinschnitz, C AF De Meyer, Simon F. Schwarz, Tobias Deckmyn, Hans Denis, Cecile V. Nieswandt, Bernhard Stoll, Guido Vanhoorelbeke, Karen Kleinschnitz, Christoph TI Binding of von Willebrand Factor to Collagen and Glycoprotein Ib alpha, But Not to Glycoprotein IIb/IIIa, Contributes to Ischemic Stroke in Mice-Brief Report SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE ischemic stroke; von Willebrand factor; gene transfer ID FACTOR-DEFICIENT MICE; THROMBUS FORMATION; TARGET; GENE; BLOCKADE AB Objective-To unravel crucial von Willebrand factor (VWF) interactions that are detrimental in stroke development. Methods and Results-VWF(-/-) mice received gene transfer to express mutants of VWF defective either in binding to fibrillar collagen, glycoprotein (GP) Ib alpha or GPIIb/IIIa, and underwent 60 minutes of transient middle cerebral artery occlusion. In VWF(-/-) mice reconstituted with VWF mutants defective in binding to collagen or GPIb alpha, protection against stroke was sustained, whereas VWF lacking the GPIIb/IIIa binding site restored full susceptibility similar to normal VWF. Conclusion-VWF-collagen and VWF-GPIb alpha (but not VWF-GPIIb/IIIa) interactions are instrumental in thrombus formation after transient middle cerebral artery occlusion, and their inhibition could be a promising target for stroke treatment. (Arterioscler Thromb Vasc Biol. 2010;30:1949-1951.) C1 [De Meyer, Simon F.; Deckmyn, Hans; Vanhoorelbeke, Karen] KULeuven, Lab Thrombosis Res, B-8500 Kortrijk, Belgium. [De Meyer, Simon F.] Harvard Univ, Sch Med, Immune Dis Inst, Boston, MA USA. [De Meyer, Simon F.] Harvard Univ, Sch Med, Program Cellular & Mol Med, Childrens Hosp Boston, Boston, MA USA. [De Meyer, Simon F.] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. [Schwarz, Tobias; Stoll, Guido; Kleinschnitz, Christoph] Univ Wurzburg, Dept Neurol, Wurzburg, Germany. [Denis, Cecile V.] Univ Paris Sud, Inst Natl Sante & Rech Med, Unite 770, F-94275 Le Kremlin Bicetre, France. [Nieswandt, Bernhard] Univ Wurzburg, Rudolf Virchow Ctr, Deutsch Forsch Gemeinschaft Res Ctr Expt Biomed, Chair Expt Biomed, Wurzburg, Germany. RP De Meyer, SF (reprint author), KULeuven, Lab Thrombosis Res, Campus Kortrijk,E Sabbelaan 53, B-8500 Kortrijk, Belgium. EM simon.demeyer@kuleuven-kortrijk.be; christoph.kleinschnitz@mail.uni-wuerzburg.de RI Denis , Cecile/A-7649-2011; Deckmyn, Hans/L-9434-2015; OI Denis , Cecile/0000-0001-5152-9156; Deckmyn, Hans/0000-0003-3952-5501; Vanhoorelbeke, Karen/0000-0003-2288-8277 FU Deutsche Forschungsgemeinschaft Bonn [SFB688 A1/B1, A13]; Flemish Fonds voor Wetenschappelijk Onderzoek (FWO), Belgium [G.0299.06] FX This work was supported by Deutsche Forschungsgemeinschaft Bonn Grants SFB688 A1/B1 (to B.N. and G. S.) and A13 (to C. K.) and by the Flemish Fonds voor Wetenschappelijk Onderzoek (FWO), Belgium, Grant G.0299.06 (to H. D.). S. F. D. M. is a postdoctoral fellow of the FWO. NR 17 TC 31 Z9 31 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD OCT PY 2010 VL 30 IS 10 BP 1949 EP 1951 DI 10.1161/ATVBAHA.110.208918 PG 3 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 650VV UT WOS:000281882800013 PM 20616311 ER PT J AU Morganroth, PA Kreider, ME Werth, VP AF Morganroth, Pamela A. Kreider, Mary Elizabeth Werth, Victoria P. TI Mycophenolate Mofetil for Interstitial Lung Disease in Dermatomyositis SO ARTHRITIS CARE & RESEARCH LA English DT Article ID RHEUMATOID-ARTHRITIS; PULMONARY-FUNCTION; METHOTREXATE AB Objective. To report our experience using mycophenolate mofetil as first-line treatment for dermatomyositis-associated interstitial lung disease. Methods. We examined the medical records of all 16 dermatomyositis patients with interstitial lung disease seen in our outpatient university hospital dermatology clinic between May 26, 2006, and May 25, 2009. In this retrospective case series, we describe the clinical course of the 4 patients with definitive evidence of interstitial lung disease on radiologic imaging who were treated with mycophenolate mofetil and had pulmonary data available to document their outcome. All of the patients also received prednisone. Results. All 3 patients with at least 1 year of followup receiving mycophenolate mofetil experienced complete normalization of pulmonary function tests (including diffusing capacity for carbon monoxide) and resolution of dyspnea. They were also able to reduce their prednisone doses. The only patient with pre- and posttreatment chest computed tomography imaging had total resolution of her interstitial opacities. The patient with only 5 months of posttreatment followup experienced an improvement in diffusing capacity for carbon monoxide from 44% to 77% predicted, but no change in dyspnea. Conclusion. These promising data indicate that mycophenolate mofetil may be a useful therapy for interstitial lung disease in patients with dermatomyositis, but larger studies are needed to more definitively evaluate the role of this medication in therapy. C1 [Morganroth, Pamela A.; Werth, Victoria P.] Philadelphia VA Med Ctr, Philadelphia, PA USA. [Morganroth, Pamela A.; Kreider, Mary Elizabeth; Werth, Victoria P.] Univ Penn, Philadelphia, PA 19104 USA. RP Werth, VP (reprint author), Hosp Univ Penn, Dept Dermatol, PCAM Suite 1-330S,3400 Civ Ctr Blvd, Philadelphia, PA 19104 USA. EM werth@mail.med.upenn.edu FU NIH [K24-AR-02207]; Department of the VA, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development FX Based on work supported by the NIH and by a Merit Review Grant from the Department of the VA, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development. Dr. Werth's work was supported by grants from the NIH (K24-AR-02207). NR 15 TC 35 Z9 37 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 2151-464X J9 ARTHRIT CARE RES JI Arthritis Care Res. PD OCT PY 2010 VL 62 IS 10 BP 1496 EP 1501 DI 10.1002/acr.20212 PG 6 WC Rheumatology SC Rheumatology GA 667IA UT WOS:000283185300019 PM 20506189 ER PT J AU Wu, Y Bauman, WA Blitzer, RD Cardozo, C AF Wu, Yong Bauman, William A. Blitzer, Robert D. Cardozo, Christopher TI Testosterone-induced hypertrophy of L6 myoblasts is dependent upon Erk and mTOR SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Muscle; Hypertrophy; Testosterone; mTOR; Erk ID ACTIVATED PROTEIN-KINASE; SKELETAL-MUSCLE; YOUNG MEN; MAMMALIAN TARGET; PATHWAY; STRENGTH; RECEPTOR; CELLS; TRANSLATION; MACHINERY AB Testosterone increases the size and strength of skeletal muscle. This study further characterized the molecular mechanisms of the anabolic actions of testosterone on a rat myoblast cell line (L6 cells). Testosterone did not induce hypertrophy in L6 cells lacking the androgen receptor (AR). Hypertrophy was prevented by the AR antagonist bicalutamide and the mTOR inhibitor rapamycin. Testosterone induced Erk phosphorylation by 2 h, and mTOR autophosphorylation was elevated within 20 min; phosphorylation of p70S6 kinase was increased by 2 h. Inhibitors of Erk or PI3K blocked tesotosterone-induced hypertrophy. Erk phosphorylation returned to baseline when media containing testosterone was replaced at 16 h with fresh media lacking testosterone; when bicalutamide was added to testosterone-enriched media at 16 h, Erk phosphorylation remained elevated. Autophosphorylation of the IGF-1 receptor was minimally altered by testosterone at 20 min and unaffected at later time points; PI3K/PDK1-dependent phosphorylation of Akt was not altered by testosterone. These findings indicate that testosterone stimulates hypertrophy of L6 myoblasts through a mechanism that requires its binding to the AR and involves a signaling cascade dependent upon Erk and mTOR which is likely activated by substances released into the extracellular space which are not IGF-1 or other ligands for receptor tyrosine kinases. Published by Elsevier Inc. C1 [Wu, Yong; Bauman, William A.; Cardozo, Christopher] James J Peters VA Med Ctr, Ctr Excellence Med Consequences Spinal Cord Injur, Dept Vet Affairs, Bronx, NY 10468 USA. [Bauman, William A.; Cardozo, Christopher] Mt Sinai Sch Med, Dept Med, New York, NY 10029 USA. [Bauman, William A.; Cardozo, Christopher] Mt Sinai Sch Med, Dept Rehabil Med, New York, NY 10029 USA. [Blitzer, Robert D.] Mt Sinai Sch Med, Dept Pharmacol & Syst Therapeut, New York, NY 10029 USA. RP Cardozo, C (reprint author), James J Peters VA Med Ctr, Ctr Excellence Med Consequences Spinal Cord Injur, Dept Vet Affairs, Room 1E-02,W Kingsbridge Rd, Bronx, NY 10468 USA. EM Chris.Cardozo@mssm.edu FU VA RRD [B4162C, B3347K, B4616R]; NIH [R01-GM054508, R21-DA029298] FX Supported by VA RR&D Grants B4162C to W.A.B. and B3347K and B4616R to C.C., respectively. R.D.B. is supported by NIH Grants R01-GM054508 and R21-DA029298. The study sponsors had no role in the design of the studies, collection, analysis or interpretation of the data, writing the manuscript or the decision to submit the manuscript for publication. NR 21 TC 23 Z9 24 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD OCT 1 PY 2010 VL 400 IS 4 BP 679 EP 683 DI 10.1016/j.bbrc.2010.08.127 PG 5 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 662YP UT WOS:000282850500039 PM 20816664 ER PT J AU Cowart, LA Gandy, JL Tholanikunnel, B Hannun, YA AF Cowart, L. Ashley Gandy, Jason L. Tholanikunnel, Baby Hannun, Yusuf A. TI Sphingolipids mediate formation of mRNA processing bodies during the heat-stress response of Saccharomyces cerevisiae SO BIOCHEMICAL JOURNAL LA English DT Article DE heat-stress response; phytosphingosine; processing body; Saccharomyces cerevisiae; sphingolipid; translation ID BUDDING YEAST; DE-NOVO; SPHINGOID BASE; P-BODIES; CERAMIDE; GRANULES; BIOSYNTHESIS; TRANSLATION; METABOLISM; PROGRAMS AB Recent work, especially in the yeast Saccharomyces cerevisiae, has demonstrated that mRNA movement from active translation to cytoplasmic granules, termed mRNA'p-bodies' (processing bodies), occurs in concert with the regulation of translation during cell stress. However, the signals regulating p-body formation are poorly defined. Recent results have demonstrated a function for sphingolipids in regulating translation during heat stress, which led to the current hypothesis that p-bodies may form during heat stress in a sphingolipid-dependent manner. In the present study, we demonstrate that mild-heat-stress-induced formation of p-bodies, as determined by localization of a GFP (green fluorescent protein)-tagged Dcp2p and RFP (red fluorescent protein)-tagged Edc3p to discrete cytoplasmic foci. Sphingoid base synthesis was required for this effect, as inhibition of sphingoid base synthesis attenuated formation of these foci during heat stress. Moreover, treatment of yeast with the exogenous sphingoid bases phyto- and dihydro-sphingosine promoted formation of p-bodies in the absence of heat stress, and the lcb4/lcb5 double-deletion yeast, which accumulates high intracellular levels of sphingoid bases, had large clearly defined p-bodies under non-stress conditions. Functionally, inhibition of sphingolipid synthesis during heat stress did not prevent translation stalling, but extended translation arrest, indicating that sphingolipids mediate translation initiation. These results are consistent with the notion that p-bodies serve not only in mRNA degradation, but also for re-routing transcripts back to active translation, and that sphingolipids play a role in this facet of the heat-stress response. Together, these results demonstrate a critical and novel role for sphingolipids in mediating p-body formation during heat stress. C1 [Cowart, L. Ashley; Gandy, Jason L.; Tholanikunnel, Baby; Hannun, Yusuf A.] Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29423 USA. [Cowart, L. Ashley] Ralph H Johnson Vet Adm Med Ctr, Charleston, SC 29401 USA. RP Hannun, YA (reprint author), Med Univ S Carolina, Dept Biochem & Mol Biol, Charleston, SC 29423 USA. EM hannun@musc.edu FU National Institutes of Health [GM63625]; American Heart Association [0555470U]; Center of Biomedical Research Excellence in Lipidomics and Pathobiology; VA Merit Award FX This work was supported by the National Institutes of Health [grant number GM63625 (to Y.A.H.)]; the American Heart Association [grant number 0555470U (to B.G.T.)]; the Center of Biomedical Research Excellence in Lipidomics and Pathobiology (to L.A.C.); and by a VA Merit Award (to L.A.C). NR 35 TC 18 Z9 18 U1 0 U2 4 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD OCT 1 PY 2010 VL 431 BP 31 EP 38 DI 10.1042/BJ20100307 PN 1 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 662ZM UT WOS:000282852800004 PM 20629639 ER PT J AU Griffitts, J Saunders, D Tesiram, YA Reid, GE Salih, A Liu, S Lydic, TA Busik, JV Kang, JX Towner, RA AF Griffitts, J. Saunders, D. Tesiram, Y. A. Reid, G. E. Salih, A. Liu, S. Lydic, T. A. Busik, J. V. Kang, J. X. Towner, R. A. TI Non-mammalian fat-1 gene prevents neoplasia when introduced to a mouse hepatocarcinogenesis model Omega-3 fatty acids prevent liver neoplasia SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS LA English DT Article DE Omega-3 fatty acids; Liver cancer; HCC, Fat-1; TGF-alpha/c-myc; Transgenic mouse model ID MAGNETIC-RESONANCE-SPECTROSCOPY; TRANSGENIC MICE RICH; GROWTH-FACTOR-ALPHA; FATTY-ACIDS; HEPATOCELLULAR CARCINOMAS; RAT HEPATOCARCINOGENESIS; PHOSPHOLIPID-METABOLISM; PROSTATE-CANCER; IN-VIVO; KAPPA-B AB We investigated the effect of a non-mammalian omega-3 desaturase in a mouse hepatocarcinogenesis model. Mice containing double mutations (DM) in c-myc and TGF-alpha (transforming growth factor-a), leading to liver neoplasia, were crossed with mice containing omega-3 desaturase. MRI analysis of triple mutant (TM) mice showed the absence of neoplasia at all time points for 92% of mice in the study. Pathological changes of TM (TGF alpha/c-myc/fat-1) mouse liver tissue was similar to control mouse liver tissue. Magnetic resonance spectroscopy (MRS) measurements of unsaturated fatty acids found a significant difference (p<0.005) between DM and TM transgenic (Tg) mice at 34 and 40 weeks of age. HPLC analysis of mouse liver tissue revealed markedly decreased levels of omega-6 fatty acids in TM mice when compared to DM (TGF alpha/c-myc) and control (CD1) mice. Mass spectrometry (MS) analysis indicated significantly decreased 16:0/20:4 and 18:1/20:4 and elevated 16:0/22:6 fatty acyl groups in both GPCho and GPEtn, and elevated 16:0/20:5, 18:0/18:2, 18:0/18:1 and 18:0/22:6 in GPCho, within TM mice compared to DM mice. Total fatty acid analysis indicated a significant decrease in 18:1n9 in TM mice compared to DM mice. Western blot analysis of liver tissue showed a significant (p<0.05) decrease in NF-kappa B (nuclear factor-kappa B) levels at 40 weeks of age in TM mice compared to DM mice. Microarray analysis of TM versus DM mice livers at 40 weeks revealed alterations in genes involved in cell cycle regulation, cell-to-cell signaling, p53 signaling, and arachidonic acid (20:4) metabolism. Endogenous omega-3 fatty acids were found to prevent HCC development in mice. (C) 2010 Elsevier B.V. All rights reserved. C1 [Griffitts, J.; Saunders, D.; Tesiram, Y. A.; Towner, R. A.] OMRF, Adv Magnet Resonance Ctr, Oklahoma City, OK 73104 USA. [Griffitts, J.; Towner, R. A.] Univ Oklahoma, Hlth Sci Ctr, Dept Pathol, Oklahoma City, OK 73104 USA. [Reid, G. E.; Salih, A.; Liu, S.] Michigan State Univ, Dept Chem, E Lansing, MI 48824 USA. [Reid, G. E.] Michigan State Univ, Dept Biochem & Mol Biol, E Lansing, MI 48824 USA. [Lydic, T. A.; Busik, J. V.] Michigan State Univ, Dept Physiol, E Lansing, MI 48824 USA. [Kang, J. X.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Lab Lipid Med & Technol, Charlestown, MA 02129 USA. RP Towner, RA (reprint author), OMRF, Adv Magnet Resonance Ctr, 825 NE 13th St, Oklahoma City, OK 73104 USA. EM Jeff-Griffitts@omrf.org; Yasvir-Tesiram@omrf.org; reid@chemistry.msu.edu; busik@msu.edu; jxkang@partners.org; Rheal-Towner@omrf.org RI Tesiram, Yasvir/B-7332-2016; OI Tesiram, Yasvir/0000-0003-3008-2927; Busik, Julia/0000-0003-3453-7124; Reid, Gavin/0000-0002-9675-1444 FU OMRF; Oklahoma Center for the Advancement of Sciences and Technology (OCAST); National Institutes of Health [RR-025386, CA113605] FX TGF alpha/c-myc mice were kindly obtained from Dr. S.S. Thorgeirsson at the National Cancer Center (NCI), Bethesda, Maryland. The authors would like to thank the OMRF microarray core-facility, directed by Dr. Bart Frank, for their invaluable assistance. We would also like to thank Dr. Charles Stewart for his help in preparing liver tissue for microarray analysis, and Ms. Jenny Oblander for her assistance in preparing and staining tissue for histologic analysis. We would also like to thank Dr. Robert E. Anderson at the Dean McGee Eye Institute at the University of Oklahoma Health Sciences Center for his input on the use of the Fat-1 transgenic mouse model. Support for the studies was provided by funding from OMRF, the Oklahoma Center for the Advancement of Sciences and Technology (OCAST), grant of fMRI-2, and the National Institutes of Health (RR-025386 to GER, JVB and RAT; CA113605 to JXK). NR 44 TC 16 Z9 19 U1 2 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1388-1981 J9 BBA-MOL CELL BIOL L JI Biochim. Biophys. Acta Mol. Cell Biol. Lipids PD OCT PY 2010 VL 1801 IS 10 BP 1133 EP 1144 DI 10.1016/j.bbalip.2010.06.008 PG 12 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 643AW UT WOS:000281265600004 PM 20620224 ER PT J AU Gotz, J Gladbach, A Pennanen, L van Eersel, J Schild, A David, D Ittner, LM AF Goetz, Juergen Gladbach, Amadeus Pennanen, Luis van Eersel, Janet Schild, Andreas David, Della Ittner, Lars M. TI Animal models reveal role for tau phosphorylation in human disease SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE LA English DT Article DE Alzheimer's disease; Amyloid; Drosophila; Frontotemporal dementia; Kinase; Mice; Nematode; Phosphatase; Phosphorylation; Tau; Transgenic ID PROTEIN PHOSPHATASE 2A; PAIRED-HELICAL-FILAMENT; GLYCOGEN-SYNTHASE KINASE-3-BETA; CYCLIN-DEPENDENT KINASE-5; SUBUNIT C-ALPHA; NEUROFIBRILLARY TANGLE FORMATION; CAENORHABDITIS-ELEGANS MODEL; TERMINAL LEUCINE RESIDUE; TRIPLE-TRANSGENIC MODEL; ALZHEIMERS-DISEASE AB Many proteins that are implicated in human disease are posttranslationally modified. This includes the microtubule-associated protein tau that is deposited in a hyperphosphorylated form in brains of Alzheimer's disease patients. The focus of this review article is on the physiological and pathological phosphorylation of tau; the relevance of aberrant phosphorylation for disease; the role of kinases and phosphatases in this process; its modeling in transgenic mice, flies, and worms; and implications of phosphorylation for therapeutic intervention. (C) 2009 Elsevier B.V. All rights reserved. C1 [Goetz, Juergen; Gladbach, Amadeus; van Eersel, Janet; Ittner, Lars M.] Univ Sydney, Brain & Mind Res Inst, Alzheimers & Parkinsons Dis Lab, Camperdown, NSW 2050, Australia. [Pennanen, Luis] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94158 USA. [Schild, Andreas] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA USA. RP Gotz, J (reprint author), Univ Sydney, Brain & Mind Res Inst, Alzheimers & Parkinsons Dis Lab, 100 Mallett St, Camperdown, NSW 2050, Australia. EM jgoetz@med.usyd.edu.au RI Gotz, Jurgen/C-2448-2014; OI Gotz, Jurgen/0000-0001-8501-7896; Ittner, Lars/0000-0001-6738-3825 FU University of Sydney; National Health & Medical Research Council (NHMRC); Australian Research Council (ARC); New South Wales Government through the Ministry for Science and Medical Research; Nerve Research Foundation; Medical Foundation (University of Sydney); Judith Jane Mason & Harold Stannett Williams Memorial Foundation FX J.G. is a Medical Foundation Fellow. This work has been supported by the University of Sydney, the National Health & Medical Research Council (NHMRC), the Australian Research Council (ARC), the New South Wales Government through the Ministry for Science and Medical Research (BioFirst Program), the Nerve Research Foundation, the Medical Foundation (University of Sydney), and the Judith Jane Mason & Harold Stannett Williams Memorial Foundation. L.M.I. has been supported by the NHMRC and ARC. NR 187 TC 39 Z9 39 U1 1 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4439 J9 BBA-MOL BASIS DIS JI Biochim. Biophys. Acta-Mol. Basis Dis. PD OCT PY 2010 VL 1802 IS 10 SI SI BP 860 EP 871 DI 10.1016/j.bbadis.2009.09.008 PG 12 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 650DC UT WOS:000281827600008 PM 19751831 ER PT J AU Shankar, R Parkinson, H Burdett, T Hastings, E Liu, JM Miller, M Srinivasa, R White, J Brazma, A Sherlock, G Stoeckert, CJ Ball, CA AF Shankar, Ravi Parkinson, Helen Burdett, Tony Hastings, Emma Liu, Junmin Miller, Michael Srinivasa, Rashmi White, Joseph Brazma, Alvis Sherlock, Gavin Stoeckert, Christian J., Jr. Ball, Catherine A. TI Annotare-a tool for annotating high-throughput biomedical investigations and resulting data SO BIOINFORMATICS LA English DT Article ID MICROARRAY DATA; MAGE-TAB; ONTOLOGY; FORMAT; SUITE AB Computational methods in molecular biology will increasingly depend on standards-based annotations that describe biological experiments in an unambiguous manner. Annotare is a software tool that enables biologists to easily annotate their high-throughput experiments, biomaterials and data in a standards-compliant way that facilitates meaningful search and analysis. C1 [Shankar, Ravi; Ball, Catherine A.] Stanford Univ, Dept Biochem, Sch Med, Stanford, CA 94305 USA. [Parkinson, Helen; Burdett, Tony; Hastings, Emma; Brazma, Alvis] European Bioinformat Inst, Cambridge, England. [Liu, Junmin; Stoeckert, Christian J., Jr.] Univ Penn, Sch Med, Dept Genet, Penn Ctr Bioinformat, Philadelphia, PA 19104 USA. [Miller, Michael] Teranode Inc, Seattle, WA USA. [Srinivasa, Rashmi] 5AM Solut Inc, Reston, VA USA. [White, Joseph] Dana Farber Canc Inst, Boston, MA 02115 USA. [Sherlock, Gavin] Stanford Univ, Dept Genet, Sch Med, Stanford, CA 94305 USA. RP Shankar, R (reprint author), Stanford Univ, Dept Biochem, Sch Med, Stanford, CA 94305 USA. EM rshankar@stanford.edu RI Sherlock, Gavin/E-9110-2012; OI Hastings, Emma/0000-0001-9927-8560; Burdett, Anthony/0000-0002-2513-5396; Parkinson, Helen/0000-0003-3035-4195; Sherlock, Gavin/0000-0002-1692-4983; Brazma, Alvis/0000-0001-5988-7409 FU US National Institutes of Health (the National Human Genome Research Institute, the National Institute of Biomedical Imaging and Bioengineering and the National Cancer Institute) [P41 HG003619]; EC [226073]; EMBL FX US National Institutes of Health (the National Human Genome Research Institute, the National Institute of Biomedical Imaging and Bioengineering and the National Cancer Institute) [grant number P41 HG003619]. EC Funding SLING contract number (to E.H. 226073), and EMBL funding (to T.B. and H.P.). NR 9 TC 7 Z9 7 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD OCT PY 2010 VL 26 IS 19 BP 2470 EP 2471 DI 10.1093/bioinformatics/btq462 PG 2 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 654LO UT WOS:000282170000021 PM 20733062 ER PT J AU Reid, MA Stoeckel, LE White, DM Avsar, KB Bolding, MS Akella, NS Knowlton, RC den Hollander, JA Lahti, AC AF Reid, Meredith A. Stoeckel, Luke E. White, David M. Avsar, Kathy B. Bolding, Mark S. Akella, N. Shastry Knowlton, Robert C. den Hollander, Jan A. Lahti, Adrienne C. TI Assessments of Function and Biochemistry of the Anterior Cingulate Cortex in Schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Article DE Anterior cingulate cortex; functional magnetic resonance imaging; magnetic resonance spectroscopy; adults; N-acetylaspartate; glutamate; schizophrenia ID MAGNETIC-RESONANCE-SPECTROSCOPY; N-ACETYLASPARTATE MEASURES; AXONAL METABOLIC RECOVERY; MEDIAL FRONTAL-CORTEX; PREFRONTAL CORTEX; MULTIPLE-SCLEROSIS; PROTON MRS; H-1 MRS; 1ST-EPISODE SCHIZOPHRENIA; RESPONSE CONFLICT AB Background: Neuroimaging and electrophysiologic studies have consistently provided evidence of impairment in anterior cingulate cortex/medial frontal cortex function in people with schizophrenia. In this study, we sought to clarify the nature of this abnormality by combining proton magnetic resonance spectroscopy (1H-MRS) with functional magnetic resonance imaging (fMRI) at 3T. Methods: We used single-voxel MRS acquired in the dorsal anterior cingulate cortex and fMRI during performance of a Stroop color-naming task to investigate the neurochemistry and functional response of the anterior cingulate cortex/medial frontal cortex in 26 stable, medicated subjects with schizophrenia and 23 matched healthy control subjects. Results: In schizophrenia subjects, we found decreased blood oxygen level dependent signal in the medial frontal wall, with significant clusters restricted to more dorsal regions compared with healthy subjects. In addition, we observed a trend-level decrease in N-acetylaspartate/creatine (NAA/Cr) levels and a significant positive correlation between NAA/Cr level and the blood oxygen level-dependent signal in schizophrenia subjects that did not exist in healthy subjects. Furthermore, in this group of medicated subjects, we did not find evidence of decreased glutamate + glutamine(Glx)/Cr levels, but there was a significant negative correlation between Glx/Cr levels and negative symptoms. Conclusions: Our results suggest that abnormal NAA levels, which may reflect a neuronal dysfunction related to schizophrenia, affect neuronal physiology, as evidenced by reduced blood oxygen level dependent response. C1 [Reid, Meredith A.; White, David M.; Avsar, Kathy B.; Bolding, Mark S.; Lahti, Adrienne C.] Univ Alabama, Dept Psychiat & Behav Neurobiol, Birmingham, AL 35294 USA. [Reid, Meredith A.] Univ Alabama, Dept Biomed Engn, Birmingham, AL 35294 USA. [Stoeckel, Luke E.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA. [Avsar, Kathy B.] Univ Alabama, Dept Psychol, Birmingham, AL 35294 USA. [Bolding, Mark S.] Univ Alabama, Dept Vis Sci, Birmingham, AL 35294 USA. [Akella, N. Shastry] Med Metr Inc, Houston, TX USA. [Knowlton, Robert C.] Univ Alabama, Dept Neurol, Birmingham, AL 35294 USA. [den Hollander, Jan A.] Univ Alabama, Dept Med, Birmingham, AL 35294 USA. RP Lahti, AC (reprint author), Univ Alabama, Dept Psychiat & Behav Neurobiol, 501 1530 3rd Ave S, Birmingham, AL 35294 USA. EM alahti@uab.edu OI White, David/0000-0002-6372-5311 FU University of Alabama Health Services Foundation; Institute of Mental Health [R01 MH081014]; National Institute of Health (NIH) [R01 NCI141663, R01 NS053998, U01 NS058634]; Pfizer FX This work was supported by a University of Alabama Health Services Foundation General Endowment Fund Scholar Award and the National Institute of Mental Health (Grant No. R01 MH081014 to ACT). We thank all the volunteers with schizophrenia who so gracefully took part in this project and the staff of the Community Psychiatry Program at the University of Alabama at Birmingham. We also thank Dr. Rosalyn Weller for editorial help and Dr. Richard Kennedy for statistical assistance.; Over the past 2 years, ACL has received research funds from a University of Alabama Health Services Foundation General Endowment Fund Scholar Award, the National Institute of Mental Health Grant No. R01 MH081014, the National Institute of Health (NIH) Grant No. R01 NCI141663, and an investigator-initiated grant from Pfizer. RCK works as a neurology subspecialist in epilepsy (35% effort), performs neuroimaging in his clinical practice (10% effort), has received honoraria from UCB Pharma, is funded by NIH Grant Nos. R01 NS053998 and U01 NS058634, and is conducting clinical trial research for EISAI Pharmaceuticals, Protocols E2007-G000-304 and 307. All other authors reported no biomedical financial interests or potential conflicts of interest. NR 105 TC 51 Z9 53 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD OCT 1 PY 2010 VL 68 IS 7 BP 625 EP 633 DI 10.1016/j.biopsych.2010.04.013 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 656SM UT WOS:000282356900007 PM 20570244 ER PT J AU Davids, MS Case, C Hornung, R Chao, NJ Chute, JP Coleman, CN Weisdorf, D Confer, DL Weinstock, DM AF Davids, Matthew S. Case, Cullen, Jr. Hornung, Raymond, III Chao, Nelson J. Chute, John P. Coleman, C. Norman Weisdorf, Daniel Confer, Dennis L. Weinstock, David M. TI Assessing Surge Capacity for Radiation Victims with Marrow Toxicity SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Nuclear; Response; Transplantation; Neutropenia; Tabletop ID MEDICAL-MANAGEMENT; COMBINED-INJURY; CARE; BIODOSIMETRY; PREPAREDNESS; CONTINGENCY; TERRORISM; STANDARDS; DISASTERS; LESSONS AB Hematologists/oncologists would provide essential care for victims of a catastrophic radiation incident, such as the detonation of an improvised nuclear device (IND). The US Radiation Injury Treatment Network (RITN) is a voluntary consortium of 37 academic medical centers, 8 blood donor centers, and 7 umbilical cord banks focused on preparedness for radiation incidents. The RITN conducted 2 tabletop exercises to evaluate response capability after a hypothetical IND detonation in a U.S. city. In the 2008 exercise, medical centers voluntarily accepted 1757 victims at their institutions, a small fraction of the number in need. In the 2009 exercise, each center was required to accept 300 victims. In response, the centers outlined multiple strategies to increase bed availability, extend staff and resources, and support family and friends accompanying transferred victims. The exercises highlighted shortcomings in current planning and future steps for improving surge capacity that are applicable to various mass casualty scenarios. Biol Blood Marrow Transplant 16: 1436-1441 (2010) (c) 2010 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved. C1 [Davids, Matthew S.; Weinstock, David M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Case, Cullen, Jr.; Hornung, Raymond, III; Confer, Dennis L.] Natl Marrow Donor Program, Minneapolis, MN USA. [Chao, Nelson J.; Chute, John P.] Duke Univ Med Ctr, Adult Bone Marrow & Stem Cell Transplantat Progra, Durham, NC USA. [Coleman, C. Norman] Dept Hlth & Human Serv, Off Assistant Secretary Preparedness & Response, Washington, DC USA. [Weisdorf, Daniel] Univ Minnesota Blood & Marrow Transplant Program, Dept Med, Radiat Injury Treatment Network, Minneapolis, MN USA. RP Weinstock, DM (reprint author), Dana Farber Canc Inst, Dept Med Oncol, 44 Binney St,Dana 510B, Boston, MA 02115 USA. EM DavidM_Weinstock@dfci.harvard.edu FU Office of Naval Research FX This research was supported in part by a grant from the Office of Naval Research. NR 24 TC 4 Z9 4 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD OCT PY 2010 VL 16 IS 10 BP 1436 EP 1441 DI 10.1016/j.bbmt.2010.04.007 PG 6 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 653EQ UT WOS:000282071500012 PM 20399880 ER PT J AU Navarro, WH Agovi, MA Logan, BR Ballen, K Bolwel, BJ Frangoul, H Gupta, V Hahn, T Ho, VT Juckett, M Lazarus, HM Litzow, MR Liesveld, JL Moreb, JS Marks, DI McCarthy, PL Pasquini, MC Rizzo, JD AF Navarro, Willis H. Agovi, Manza-A Logan, Brent R. Ballen, Karen Bolwel, Brian J. Frangoul, Haydar Gupta, Vikas Hahn, Theresa Ho, Vincent T. Juckett, Mark Lazarus, Hillard M. Litzow, Mark R. Liesveld, Jane L. Moreb, Jan S. Marks, David I. McCarthy, Philip L. Pasquini, Marcelo C. Rizzo, J. Douglas TI Obesity Does Not Preclude Safe and Effective Myeloablative Hematopoietic Cell Transplantation (HCT) for Acute Myelogenous Leukemia (AML) in Adults SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE Hematopoietic cell transplantation; Obesity; Outcomes; Acute myelogenous leukemia ID METABOLIC SYNDROME; OVERWEIGHT; METAANALYSIS; PREVALENCE; EPIDEMIC; INDEX; GRAFT; RISK AB The incidence of excessive adiposity is increasing worldwide, and is associated with numerous adverse health outcomes. We compared outcomes by body mass index (BMI) for adult patients with acute myelogenous leukemia (AML) who underwent autologous (auto, n = 373), related donor (RD, n = 2041), or unrelated donor (URD, n = 1801) allogeneic myeloablative hematopoietic cell transplantation (HCT) using bone marrow or peripheral blood stem cells reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) from 1995 to 2004. Four weight groups by BMI (kg/m(2)) were defined: underweight <18 kg/m(2); normal 18-25 kg/m(2); overweight >25-30 kg/m(2); and obese >30 kg/m(2). Multivariable analysis referenced to the normal weight group showed an increased risk of death for underweight patients in the RD group (relative risk [RR], 1.92; 95% confidence interval [CI], 1.28-2.89; P = .002), but not in the URD group. There were no other differences in outcomes among the other weight groups within the other HCT groups. Overweight and obese patients enjoyed a modest decrease in relapse incidence, although this did not translate into a survival benefit. Small numbers of patients limit the ability to better characterize the adverse outcomes seen in the underweight RD but not the underweight URD allogeneic HCT patients. Obesity alone should not be considered a barrier to HCT. Biol Blood Marrow Transplant 16: 1442-1450 (2010) (c) 2010 American Society for Blood and Marrow Transplantation C1 [Navarro, Willis H.] Natl Marrow Donor Program, Minneapolis, MN 55413 USA. [Agovi, Manza-A; Logan, Brent R.; Pasquini, Marcelo C.; Rizzo, J. Douglas] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant Res, Milwaukee, WI 53226 USA. [Ballen, Karen] Massachusetts Gen Hosp, Boston, MA 02114 USA. [Bolwel, Brian J.] Cleveland Clin Fdn, Cleveland, OH 44195 USA. [Frangoul, Haydar] Vanderbilt Univ Sch Med, Nashville, TN USA. [Gupta, Vikas] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. [Hahn, Theresa; McCarthy, Philip L.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA. [Ho, Vincent T.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Juckett, Mark] Univ Wisconsin Hosp & Clin, Madison, WI 53792 USA. [Lazarus, Hillard M.] Univ Hosp Case Med Ctr, Cleveland, OH USA. [Litzow, Mark R.] Mayo Clin, Rochester, MN USA. [Liesveld, Jane L.] Univ Rochester Med Ctr, Strong Mem Hosp, Rochester, NY USA. [Moreb, Jan S.] Univ Florida, Shands Hosp, Gainesville, FL USA. [Marks, David I.] Bristol Childrens Hosp, Bristol, Avon, England. RP Navarro, WH (reprint author), Natl Marrow Donor Program, 3001 Broadway St NE,Suite 100, Minneapolis, MN 55413 USA. EM wnavarro@nmdp.org FU National Cancer Institute (NCI) [U24-CA76518]; National Heart, Lung and Blood Institute (NHLBI); National Institute of Allergy and Infectious Diseases (NIAID); NHLBI [5U01HL069294]; NCI; Health Resources and Services Administration (HRSA/DHHS) [HHSH234200637015C]; Office of Naval Research [N00014-06-1-0704, N00014-08-1-0058]; AABB; Aetna; American Society for Blood and Marrow Transplantation; Amgen, Inc.; Anonymous donation to the Medical College of Wisconsin; Astellas Pharma US, Inc.; Baxter International, Inc.; Bayer HealthCare Pharmaceuticals; Be the Match Foundation; Biogen IDEC; BioMarin Pharmaceutical, Inc.; Biovitrum AB; BloodCenter of Wisconsin; Blue Cross and Blue Shield Association; Bone Marrow Foundation; Canadian Blood and Marrow Transplant Group; CaridianBCT; Celgene Corporation; CellGenix, GmbH; Centers for Disease Control and Prevention; Children's Leukemia Research Association; ClinImmune Labs; CTI Clinical Trial and Consulting Services; Cubist Pharmaceuticals; Cylex Inc.; CytoTherm; DOR BioPharma, Inc.; Dynal Biotech, an Invitrogen Company; Eisai, Inc.; Enzon Pharmaceuticals, Inc.; European Group for Blood and Marrow Transplantation; Gamida Cell, Ltd.; GE Healthcare; Genentech, Inc.; Genzyme Corporation; Histogenetics, Inc.; HKS Medical Information Systems; Hospira, Inc.; Infectious Diseases Society of America; Kiadis Pharma; Kirin Brewery Co., Ltd.; The Leukemia & Lymphoma Society; Merck Company; The Medical College of Wisconsin; MGI Pharma, Inc.; Michigan Community Blood Centers; Millennium Pharmaceuticals, Inc.; Miller Pharmacal Group; Milliman USA, Inc.; Miltenyi Biotec, Inc.; National Marrow Donor Program; Nature Publishing Group; New York Blood Center; Novartis Oncology; Oncology Nursing Society; Osiris Therapeutics, Inc.; Otsuka America Pharmaceutical, Inc.; Pall Life Sciences; Pfizer Inc; Saladax Biomedical, Inc.; Schering Corporation; Society for Healthcare Epidemiology of America; Soligenix, Inc.; StemCyte, Inc.; StemSoft Software, Inc.; Sysmex America, Inc.; THERAKOS, Inc.; Thermogenesis Corporation; Vidacare Corporation; Vion Pharmaceuticals, Inc.; ViraCor Laboratories; ViroPharma, Inc.; Wellpoint, Inc. FX The CIBMTR is supported by Public Health Service Grant/Cooperative Agreement U24-CA76518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI), and the National Institute of Allergy and Infectious Diseases (NIAID); a Grant/Cooperative Agreement 5U01HL069294 from NHLBI and NCI; a contract HHSH234200637015C with Health Resources and Services Administration (HRSA/DHHS); 2 grants N00014-06-1-0704 and N00014-08-1-0058 from the Office of Naval Research; and grants from AABB; Aetna; American Society for Blood and Marrow Transplantation; Amgen, Inc.; Anonymous donation to the Medical College of Wisconsin; Astellas Pharma US, Inc.; Baxter International, Inc.; Bayer HealthCare Pharmaceuticals; Be the Match Foundation; Biogen IDEC; BioMarin Pharmaceutical, Inc.; Biovitrum AB; BloodCenter of Wisconsin; Blue Cross and Blue Shield Association; Bone Marrow Foundation; Canadian Blood and Marrow Transplant Group; CaridianBCT; Celgene Corporation; CellGenix, GmbH; Centers for Disease Control and Prevention; Children's Leukemia Research Association; ClinImmune Labs; CTI Clinical Trial and Consulting Services; Cubist Pharmaceuticals; Cylex Inc.; CytoTherm; DOR BioPharma, Inc.; Dynal Biotech, an Invitrogen Company; Eisai, Inc.; Enzon Pharmaceuticals, Inc.; European Group for Blood and Marrow Transplantation; Gamida Cell, Ltd.; GE Healthcare; Genentech, Inc.; Genzyme Corporation; Histogenetics, Inc.; HKS Medical Information Systems; Hospira, Inc.; Infectious Diseases Society of America; Kiadis Pharma; Kirin Brewery Co., Ltd.; The Leukemia & Lymphoma Society; Merck & Company; The Medical College of Wisconsin; MGI Pharma, Inc.; Michigan Community Blood Centers; Millennium Pharmaceuticals, Inc.; Miller Pharmacal Group; Milliman USA, Inc.; Miltenyi Biotec, Inc.; National Marrow Donor Program; Nature Publishing Group; New York Blood Center; Novartis Oncology; Oncology Nursing Society; Osiris Therapeutics, Inc.; Otsuka America Pharmaceutical, Inc.; Pall Life Sciences; Pfizer Inc; Saladax Biomedical, Inc.; Schering Corporation; Society for Healthcare Epidemiology of America; Soligenix, Inc.; StemCyte, Inc.; StemSoft Software, Inc.; Sysmex America, Inc.; THERAKOS, Inc.; Thermogenesis Corporation; Vidacare Corporation; Vion Pharmaceuticals, Inc.; ViraCor Laboratories; ViroPharma, Inc.; and Wellpoint, Inc. NR 21 TC 30 Z9 31 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 OCT PY 2010 VL 16 IS 10 BP 1442 EP 1450 DI 10.1016/j.bbmt.2010.04.009 PG 9 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 653EQ UT WOS:000282071500013 PM 20412867 ER PT J AU Morley, JF Duda, JE AF Morley, James F. Duda, John E. TI Olfaction as a biomarker in Parkinson's disease SO BIOMARKERS IN MEDICINE LA English DT Review DE diagnosis; dopaminergic functional imaging; neuropathology; olfaction; olfactory bulb; Parkinson's disease; parkinsonian disorders; pathophysiology; smell ID SLEEP BEHAVIOR DISORDER; PROGRESSIVE SUPRANUCLEAR PALSY; SMELL IDENTIFICATION TEST; LEWY BODY DISORDERS; ODOR IDENTIFICATION; TRANSCRANIAL SONOGRAPHY; ALPHA-SYNUCLEINOPATHY; COGNITIVE IMPAIRMENT; CLINICAL-DIAGNOSIS; AUTONOMIC FAILURE AB Olfactory dysfunction in Parkinson's disease is common and of interest, both as a clinical finding and potential biomarker. In this article, we discuss studies characterizing the olfactory deficit in Parkinson's disease and pathological analysis that suggests the olfactory system is a likely induction site of the neurodegenerative process. These studies have enabled research to explore the potential of olfactory dysfunction as a key component in early diagnostic strategies, as a biomarker for diagnostic purposes, a predictor of clinical outcomes and a potential therapy-independent marker of disease progression. C1 [Morley, James F.; Duda, John E.] Univ Penn, Sch Med, Philadelphia VA Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, Philadelphia, PA 19104 USA. [Morley, James F.; Duda, John E.] Univ Penn, Sch Med, Dept Neurol, Philadelphia, PA 19104 USA. RP Duda, JE (reprint author), Univ Penn, Sch Med, Philadelphia VA Med Ctr, Parkinsons Dis Res Educ & Clin Ctr, Philadelphia, PA 19104 USA. EM john.duda@va.gov NR 95 TC 19 Z9 19 U1 1 U2 8 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1752-0363 J9 BIOMARK MED JI Biomark. Med. PD OCT PY 2010 VL 4 IS 5 BP 661 EP 670 DI 10.2217/BMM.10.95 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 673DD UT WOS:000283638000003 PM 20945979 ER PT J AU Cipriani, S Chen, XQ Schwarzschild, MA AF Cipriani, S. Chen, Xiqun Schwarzschild, Michael A. TI Urate: a novel biomarker of Parkinson's disease risk, diagnosis and prognosis SO BIOMARKERS IN MEDICINE LA English DT Review DE blood; cerebrospinal fluid; oxidative stress; Parkinson's disease; prognosis; substantia nigra; urate ID SERUM URIC-ACID; BLOOD-BRAIN-BARRIER; PLASMA URATE; CEREBROSPINAL-FLUID; HOMINOID EVOLUTION; HYDROXYL RADICALS; OXIDANT STRESS; IN-VIVO; ANTIOXIDANT; PROGRESSION AB A growing number of studies have correlated higher urate levels with a lower risk of developing Parkinson's disease (PD) and with a favorable rate of disease progression, indicating that urate could be an important biomarker of the pathophysiology underlying PD. Dietary and genetic determinants of urate have also been linked to a reduced risk or delayed onset of PD. Based on the known antioxidant and metal complexing properties of urate, together with evidence for oxidative stress as a contributor to neurodegeneration in PD, urate may serve as an endogenous neuroprotectant that helps reduce the risk and rate of the disease. In this article we review the convergent biological, epidemiological and clinical data that identify urate as a promising biomarker of the risk, diagnosis and prognosis of PD. C1 [Cipriani, S.; Chen, Xiqun; Schwarzschild, Michael A.] Massachusetts Gen Hosp, Boston, MA 02129 USA. RP Cipriani, S (reprint author), Massachusetts Gen Hosp, 114 16th St, Boston, MA 02129 USA. EM scipriani@partners.org FU NIH [R01NS054978, K24NS60991, R21NS058324]; Michael J Fox Foundation; American Parkinson's Disease Association; RJG Foundation FX This work was supported by grants from the NIH (R01NS054978, K24NS60991 and R21NS058324), Michael J Fox Foundation, American Parkinson's Disease Association and RJG Foundation. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 81 TC 43 Z9 47 U1 2 U2 11 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1752-0363 J9 BIOMARK MED JI Biomark. Med. PD OCT PY 2010 VL 4 IS 5 BP 701 EP 712 DI 10.2217/BMM.10.94 PG 12 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 673DD UT WOS:000283638000006 PM 20945982 ER PT J AU Zabihi, S Loeken, MR AF Zabihi, Sheller Loeken, Mary R. TI Understanding Diabetic Teratogenesis: Where Are We Now and Where Are We Going? SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Review DE diabetic pregnancy; diabetic embryopathy; neural tube defect; cardiac outflow tract defect; hyperglycemia; oxidative stress; Pax3; p53 ID NEURAL-TUBE DEFECTS; RAT EMBRYO CULTURE; DEPENDENT ANTIOXIDANT SYSTEM; TRANSPORTER GENE-EXPRESSION; FUEL-MEDIATED TERATOGENESIS; RADICAL SCAVENGING ENZYMES; MESSENGER-RNA LEVELS; IN-VITRO; MOUSE EMBRYOS; VITAMIN-E AB Maternal pregestational diabetes (type 1 or type 2) poses an increased risk for a broad spectrum of birth defects. To our knowledge, this problem first came to the attention of the Teratology Society at the 14th Annual Meeting in Vancouver, B.C. in 1974, with a presentation by Lewis Holmes, "Etiologic heterogeneity of neural tube defects". Although advances in the control of diabetes in the decades since the discovery of insulin in the 1920's have reduced the risk for birth defects during diabetic pregnancy, the increasing incidence of diabetes among women of childbearing years indicates that this cause of birth defects is a growing public health concern. Major advances in understanding how a disease of maternal fuel metabolism can interfere with embryogenesis of multiple organ systems have been made in recent years. In this review, we trace the history of the study of diabetic teratogenesis and discuss a model in which tissue-specific developmental control genes are regulated at specific times in embryonic development by glucose metabolism. The major function of such genes is to suppress apoptosis, perhaps to preserve proliferative capability, and inhibit premature senescence. Birth Defects Research (Part A) 88:779-790, 2010. (C) 2010 Wiley-Liss, Inc. C1 [Zabihi, Sheller; Loeken, Mary R.] Joslin Diabet Ctr, Sect Dev & Stem Cell Biol, Boston, MA 02215 USA. RP Loeken, MR (reprint author), Joslin Diabet Ctr, Sect Dev & Stem Cell Biol, 1 Joslin Pl, Boston, MA 02215 USA. EM mary.loeken@joslin.harvard.edu OI Loeken, Mary/0000-0002-8056-9816 FU [RO1 DK52865]; [RO1 DK58300] FX Grant support for this paper was RO1 DK52865, RO1 DK58300 (to M.R.L.). NR 146 TC 42 Z9 44 U1 0 U2 11 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD OCT PY 2010 VL 88 IS 10 SI SI BP 779 EP 790 DI 10.1002/bdra.20704 PG 12 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 673DH UT WOS:000283638500004 PM 20706996 ER PT J AU Hayes, JH Chen, MH Moran, BJ Braccioforte, MH Dosoretz, DE Salenius, S Katin, MJ Ross, R Choueiri, TK D'Amico, AV AF Hayes, Julia H. Chen, Ming-Hui Moran, Brian J. Braccioforte, Michelle H. Dosoretz, Daniel E. Salenius, Sharon Katin, Michael J. Ross, Rudi Choueiri, Toni K. D'Amico, Anthony V. TI Androgen-suppression therapy for prostate cancer and the risk of death in men with a history of myocardial infarction or stroke SO BJU INTERNATIONAL LA English DT Article DE prostate cancer; multimodal therapy; neoadjuvant treatment; side-effects; hormone antagonists ID RANDOMIZED CONTROLLED-TRIAL; DEPRIVATION THERAPY; CARDIOVASCULAR MORTALITY; HORMONAL-THERAPY; BRACHYTHERAPY; RADIATION; RADIOTHERAPY; DISEASE AB OBJECTIVE To examine the effect of short-course androgen-suppression therapy (AST) before brachytherapy on all-cause mortality (ACM) rates, stratified by the presence or absence of a history of myocardial infarction (MI) or stroke. AST is used to reduce prostate size to enable men with favourable-risk prostate cancer to undergo brachytherapy, but no disease-specific benefit has been reported for this practice, and AST use has been associated with an increased risk of ACM in some men with pre-existing cardiovascular disease. PATIENTS AND METHODS The study comprised 12 792 men with favourable-risk disease, i.e. a prostate-specific antigen (PSA) level of < 20 ng/mL, Gleason score < 7 and clinical category < T2c, treated between 1991 and 2007 at community-based medical centres with brachytherapy +/- neoadjuvant AST. Multivariable Cox regression analysis was used to assess whether there were significant associations between AST use in men with a history of MI or stroke and the risk of ACM, adjusting for age, treatment year, and known prognostic factors of prostate cancer. RESULTS After a median (interquartile range) follow-up of 3.8 (2.0-5.9) years there were 1557 deaths. The risk of ACM was lower in men with no history of MI or stroke than in those with this history, whether AST was used (adjusted hazard ratio 0.79, 95% confidence interval 0.67-0.92; P = 0.003) or not (0.74, 0.65-0.85; P < 0.001). However, men with a history of MI or stroke treated with AST had a greater risk of ACM than those not treated with AST (1.2, 1.05-1.38; P = 0.008). CONCLUSION The use of short-course AST in men with a history of MI or stroke is associated with a greater risk of ACM in men with favourable-risk prostate cancer. C1 [Hayes, Julia H.; Choueiri, Toni K.; D'Amico, Anthony V.] Dana Farber Canc Inst, Boston, MA 02115 USA. [D'Amico, Anthony V.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Chen, Ming-Hui] Univ Connecticut, Storrs, CT USA. [Moran, Brian J.; Braccioforte, Michelle H.] Prostate Canc Fdn Chicago, Westmont, IL USA. [Dosoretz, Daniel E.; Salenius, Sharon; Katin, Michael J.; Ross, Rudi] 21st Century Oncol, Ft Myers, FL USA. RP Hayes, JH (reprint author), Dana Farber Canc Inst, Dana 1230,44 Binney St, Boston, MA 02115 USA. EM Julia_Hayes@dfci.harvard.edu NR 25 TC 13 Z9 14 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1464-4096 J9 BJU INT JI BJU Int. PD OCT PY 2010 VL 106 IS 7 BP 979 EP 985 DI 10.1111/j.1464-410X.2010.09273.x PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 650LO UT WOS:000281851200007 PM 20230380 ER PT J AU King, DR Namias, N Andrews, DM AF King, David R. Namias, Nicholas Andrews, David M. TI Coagulation abnormalities following thermal injury SO BLOOD COAGULATION & FIBRINOLYSIS LA English DT Article DE burns; fibrinolysis; hypercoagulable state; prothrombin; trauma ID SMOKE-INHALATION; BURN INJURY; ARTERIAL; COMPLICATIONS; PARAMETERS; MORTALITY; TRAUMA; IMPACT; SHEEP AB Changes in coagulation may have a profound impact on outcomes following severe burns and the coagulation abnormalities after thermal injury are incompletely described. We postulated that thermal injury induces a systemic hypercoagulable state. With Institutional Review Board approval, five patients were consented for enrollment in this case series. After obtaining informed consent, blood was drawn on hospital days 1, 2, 3, 5, and 7 or until discharge if discharge was in less than 7 days. Standard coagulation testing was performed, as well as a battery of sophisticated specialized coagulation assays. Other data collected includes fluid resuscitation volumes, pharmacologic interventions, and general physiologic information. Results (n=5) demonstrate that burns less than 6% total body surface area appear to have little effect on coagulation. Burns greater than 6% appear to induce a systemic hypercoagulable state with a phase and magnitude relationship proportional to total body surface area burned. Severe burns greater than 40% appear to induce a consumptive coagulopathy. Prothrombin fragment 1.2 may represent a useful screening test for a burn-induced hypercoagulable state. Blood Coagul Fibrinolysis 21: 666669 (c) 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins. C1 [King, David R.] Massachusetts Gen Hosp, Dept Surg, Div Trauma Emergency Surg & Surg Crit Care, Boston, MA 02114 USA. [King, David R.] Harvard Univ, Sch Med, Boston, MA 02114 USA. [Namias, Nicholas] Univ Miami, Div Burns, Jackson Mem Burn Ctr, Miami, FL USA. [Andrews, David M.] Univ Miami, Dept Pathol, Jackson Mem Burn Ctr, Miami, FL USA. RP King, DR (reprint author), Massachusetts Gen Hosp, Div Trauma, 165 Cambridge St,Suite 810, Boston, MA 02114 USA. EM dking3@partners.org OI King, David/0000-0003-1028-1478 NR 15 TC 12 Z9 13 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0957-5235 J9 BLOOD COAGUL FIBRIN JI Blood Coagul. Fibrinolysis PD OCT PY 2010 VL 21 IS 7 BP 666 EP 669 DI 10.1097/MBC.0b013e32833ceb08 PG 4 WC Hematology SC Hematology GA 658IK UT WOS:000282483500008 PM 20689402 ER PT J AU Fasler-Kan, E Suenderhauf, C Barteneva, N Poller, B Gygax, D Huwyler, J AF Fasler-Kan, Elizaveta Suenderhauf, Claudia Barteneva, Natasha Poller, Birk Gygax, Daniel Huwyler, Joerg TI Cytokine signaling in the human brain capillary endothelial cell line hCMEC/D3 SO BRAIN RESEARCH LA English DT Article DE Blood-brain barrier; Neurovascular disease; JAK/STAT; Interferon; Cytokine; Signaling; hCMEC/D3 ID CENTRAL-NERVOUS-SYSTEM; INTERFERON-GAMMA; IN-VITRO; PARKINSONS-DISEASE; BARRIER; EXPRESSION; ALPHA; MIGRATION; PATHWAY; MODEL AB Brain microvascular endothelial cells are part of the blood-brain barrier and participate actively in immunological processes including cytokine-mediated inflammatory reactions. Using the human brain capillary endothelial cell line hCMEC/D3, activation of JAK/STAT signaling pathways were studied in response to stimulation by cytokines. The phenotype of hCMEC/D3 cells was confirmed by flow cytometry analysis of cell adhesion factors (cluster of differentiation molecules CD31 and CD34) and the von Willebrand factor endothelial marker was detected by immunofluorescence. Strong STAT1, STAT6 and STAT3 activation was observed in response to interferon-gamma (IFN-gamma), interleukin 4 (IL-4) and interleukin 6 (IL-6), respectively. Nuclear translocation of phosphorylated STAT proteins was visualized by confocal microscopy. Treatment of hCMEC/D3 cells with IFN-gamma resulted in interferon-induced upregulation of major histocompatibility complex (MHC) class I within 48 h. Interferon-alpha (IFN-alpha) did not activate STAT1 or STAT3 nor did it induce MHC class I upregulation. Therefore, hCMEC/D3 cells were judged to be non-responsive to IFN-alpha. We also observed that hCMEC/D3 cells exhibit functional expression of alternative cytokine signal transduction pathways (i.e. TNE-alpha mediated activation of NF-kappa B). Together these results indicate that human blood-brain barrier hCMEC/D3 cells are responsive towards stimulation with various cytokines. We conclude that this unique cell line can be used to explore in vitro human blood-brain barrier functionality under proinflammatory conditions. (C) 2010 Elsevier B.V. All rights reserved. C1 [Poller, Birk; Huwyler, Joerg] Univ Basel, Dept Pharmaceut Sci, CH-4056 Basel, Switzerland. [Suenderhauf, Claudia; Huwyler, Joerg] Univ Appl Sci NW Switzerland FHNW, Inst Pharmaceut Technol, CH-4123 Muttenz, Switzerland. [Fasler-Kan, Elizaveta; Gygax, Daniel] Univ Appl Sci NW Switzerland FHNW, Inst Chem & Bioanalyt, CH-4123 Muttenz, Switzerland. [Barteneva, Natasha] Harvard Univ, Sch Med, Children Hosp Boston, Dept Pathol,Immune Dis Inst, Boston, MA 02115 USA. [Barteneva, Natasha] Harvard Univ, Sch Med, Children Hosp Boston, Dept Pathol,Program Cellular & Mol Biol, Boston, MA 02115 USA. RP Huwyler, J (reprint author), Univ Basel, Dept Pharmaceut Sci, Klingelbergstr 50, CH-4056 Basel, Switzerland. EM joerg.huwyler@unibas.ch RI Huwyler, Joerg/C-6573-2013; Suenderhauf, Claudia/K-1990-2016 FU F. Hoffmann-La Roche Ltd. FX Financial support of F. Hoffmann-La Roche Ltd. is acknowledged. We would like to thank Dr. Philippe Coassolo (Roche Ltd.), Dr. Christoph Funk (Roche Ltd.) and Beat Erne (confocal microscopy core unit at the University Hospital Basel). Ronald Tynes (University of Applied Sciences) assisted with proof-reading of the manuscript. E. Fasler-Kan, C. Suenderhauf and J. Huwyler contributed equally to the present work. NR 45 TC 14 Z9 14 U1 1 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD OCT 1 PY 2010 VL 1354 BP 15 EP 22 DI 10.1016/j.brainres.2010.07.077 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 654IT UT WOS:000282162400002 PM 20692239 ER PT J AU Vedeniapin, A Cheng, L George, MS AF Vedeniapin, Andrei Cheng, Laura George, Mark S. TI Feasibility of simultaneous cognitive behavioral therapy and left prefrontal rTMS for treatment resistant depression SO BRAIN STIMULATION LA English DT Article ID TRANSCRANIAL MAGNETIC STIMULATION; CORTEX C1 [Vedeniapin, Andrei] Med Univ S Carolina, IOP, Dept Psychiat & Behav Sci, Charleston, SC 29425 USA. [Cheng, Laura] Med Univ S Carolina, Coll Med, Charleston, SC 29425 USA. [George, Mark S.] Ralph H Johnson VA Med Ctr, Charleston, SC USA. RP Vedeniapin, A (reprint author), Med Univ S Carolina, IOP, Dept Psychiat & Behav Sci, 519 N,67 President St, Charleston, SC 29425 USA. EM vedeniap@musc.edu FU National Institute on Drug Abuse [R25 DA020537]; Neuronetics; Brainsway; Principal Investigator for a Veterans Affairs [VA CSP 556] FX Partial funding to Dr. Vedeniapin was provided by National Institute on Drug Abuse grant R25 DA020537.; Mark George is an unpaid consultant to several TMS manufacturers (Neuronetics. Brainsway, Neostim, Neosync). Neuronetics loaned the TMS equipment for a recent National Institutes of Health-sponsored TMS trial in depression that Dr. George chaired. The brain stimulation laboratory is conducting a depression clinical trial funded by Brainsway. Dr. George is on the executive committee and is a site Principal Investigator for a Veterans Affairs funded multisite cooperative studies trial of TMS to treat depressed veterans (VA CSP 556). NR 14 TC 11 Z9 12 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1935-861X J9 BRAIN STIMUL JI Brain Stimul. PD OCT PY 2010 VL 3 IS 4 BP 207 EP 210 DI 10.1016/j.brs.2010.03.005 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 675GG UT WOS:000283814200004 PM 20965449 ER PT J AU Phillips, KA Ribi, K Sun, ZX Stephens, A Thompson, A Harvey, V Thurlimann, B Cardoso, F Pagani, O Coates, AS Goldhirsch, A Price, KN Gelber, RD Bernhard, J AF Phillips, Kelly-Anne Ribi, Karin Sun, Zhuoxin Stephens, Alisa Thompson, Alastair Harvey, Vernon Thuerlimann, Beat Cardoso, Fatima Pagani, Olivia Coates, Alan S. Goldhirsch, Aron Price, Karen N. Gelber, Richard D. Bernhard, Juerg TI Cognitive function in postmenopausal women receiving adjuvant letrozole or tamoxifen for breast cancer in the BIG 1-98 randomized trial SO BREAST LA English DT Article DE Cognitive function; Breast cancer; Aromatase inhibitor; Tamoxifen; Letrozole; Quality of life ID THERAPY; MEMORY; ESTROGEN; ANASTROZOLE; IMPAIRMENT; ESTRADIOL; DEMENTIA; BRAIN; RATS AB Cognitive function in postmenopausal women receiving letrozole or tamoxifen as adjuvant endocrine treatment was compared during the fifth year of treatment in a substudy of the BIG 1-98 trial. In BIG 1-98 patients were randomized to receive adjuvant (A) 5-years tamoxifen, (B) 5-years letrozole, (C) 2-years tamoxifen followed by 3-years letrozole, or (D) 2-years letrozole followed by 3-years tamoxifen. The primary comparison was the difference in composite score for patients taking letrozole (B + C: N = 65) vs. tamoxifen (A + D; N = 55). The patients taking letrozole had better overall cognitive function than those taking tamoxifen (difference in mean composite z-scores = 0.28, P = 0.04, 95% Cl: 0.02, 0.54, Cohen's D = 0.40 indicating small to moderate effect). In this substudy, breast cancer patients taking adjuvant letrozole during the fifth year of treatment had better cognitive function than those taking tamoxifen, suggesting aromatase inhibitors do not adversely impact cognition compared with tamoxifen. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Ribi, Karin; Bernhard, Juerg] IBCSG Coordinating Ctr, CH-3008 Bern, Switzerland. [Bernhard, Juerg] Univ Hosp Bern, Inselspital, Dept Med Oncol, CH-3010 Bern, Switzerland. [Phillips, Kelly-Anne] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. [Phillips, Kelly-Anne] Univ Melbourne, Melbourne, Vic, Australia. [Sun, Zhuoxin; Gelber, Richard D.] Dana Farber Canc Inst, IBCSG Stat Ctr, Boston, MA 02115 USA. [Stephens, Alisa] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. [Thompson, Alastair] Univ Dundee, Ninewells Hosp, Dundee, Scotland. [Harvey, Vernon] Auckland City Hosp, Auckland, New Zealand. [Thuerlimann, Beat] Kantonsspital, Breast Ctr, St Gallen, Switzerland. [Thuerlimann, Beat; Pagani, Olivia] Swiss Grp Clin Canc Res SAKK, Bern, Switzerland. [Cardoso, Fatima] Inst Jules Bordet, Dept Med Oncol, B-1000 Brussels, Belgium. [Pagani, Olivia] Osped Italian, Oncol Inst So Switzerland, Lugano, Switzerland. [Coates, Alan S.] IBCSG, Bern, Switzerland. [Coates, Alan S.] Univ Sydney, Sydney, NSW 2006, Australia. [Goldhirsch, Aron] European Inst Oncol, Dept Med, Milan, Italy. [Goldhirsch, Aron] Oncol Inst So Switzerland, Bellinzona, Switzerland. [Price, Karen N.; Gelber, Richard D.] Frontier Sci & Technol Res Fdn Inc, Boston, MA USA. RP Bernhard, J (reprint author), IBCSG Coordinating Ctr, Effingerstr 40, CH-3008 Bern, Switzerland. EM Kelly.Phillips@petermac.org; karin.ribi@ibcsg.org; zhuoxin@jimmy.harvard.edu; astephen@hsph.harvard.edu; a.m.thompson@dundee.ac.uk; VernonH@adhb.govt.nz; beat.thuerlimann@kssg.ch; fatima.cardoso@bordet.be; olivia.pagani@ibcsg.org; alan.coates@ibcsg.org; aron.goldhirsch@ibcsg.org; price@jimmy.harvard.edu; gelber@jimmy.harvard.edu; juerg.bernhard@ibcsg.org OI Phillips, Kelly-Anne/0000-0002-0475-1771; Cardoso, Fatima/0000-0002-6692-2249 FU Novartis; Swedish Cancer Society; Cancer Council Australia; Australian New Zealand Breast Cancer Trials Group; Frontier Science and Technology Research Foundation; Swiss Group for Clinical Cancer Research (SAKK); National Cancer Institute at the National Institutes of Health [CA-75362]; Cancer Research Switzerland/Oncosuisse; Foundation for Clinical Cancer Research of Eastern Switzerland (OSKK); Cancer Council Victoria FX Sources of support that require acknowledgment including grant numbers: The BIG 1-98 trial and the Cognitive Function Substudy are financed by Novartis and coordinated by IBCSG. Support for the IBCSG: Swedish Cancer Society; The Cancer Council Australia; Australian New Zealand Breast Cancer Trials Group; Frontier Science and Technology Research Foundation; Swiss Group for Clinical Cancer Research (SAKK); National Cancer Institute at the National Institutes of Health [Grant CA-75362]; Cancer Research Switzerland/Oncosuisse; and the Foundation for Clinical Cancer Research of Eastern Switzerland (OSKK); The Cancer Council Victoria, Dr John Colebatch Clinical Research Fellowship [to MAP]. NR 31 TC 34 Z9 36 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 0960-9776 J9 BREAST JI Breast PD OCT PY 2010 VL 19 IS 5 BP 388 EP 395 DI 10.1016/j.breast.2010.03.025 PG 8 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 673XF UT WOS:000283696800015 PM 20385495 ER PT J AU Morrow, PK Divers, S Provencher, L Luoh, SW Petrella, TM Giurescu, M Schmelter, T Wang, Y Hortobagyi, GN Vahdat, LT AF Morrow, Phuong K. Divers, Stephen Provencher, Louise Luoh, Shiuh-Wen Petrella, Teresa M. Giurescu, Marius Schmelter, Thomas Wang, Yao Hortobagyi, Gabriel N. Vahdat, Linda T. TI Phase II study evaluating the efficacy and safety of sagopilone (ZK-EPO) in patients with metastatic breast cancer that has progressed following chemotherapy SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE Phase II; Sagopilone; Epothilones; Breast cancer; Metastatic ID IXABEPILONE BMS-247550; OVARIAN-CANCER; SOLID TUMORS; NEUROPATHY; TAXANE; ANTHRACYCLINE; CAPECITABINE; CISPLATIN; RESISTANT; AGENT AB Sagopilone is a novel, fully synthetic epothilone that has shown promising preclinical activity in a range of tumor models, including platinum-resistant ovarian cancer and metastatic breast cancer (MBC). This open-label, multicenter, Phase II study investigated the efficacy, safety, and tolerability of sagopilone administered to patients with MBC. Women with MBC whose previous chemotherapy regimen included a taxane and an anthracycline received sagopilone 16 or 22 mg/m(2) as a 3-h intravenous infusion every 21 days. Efficacy (using modified Response Evaluation Criteria in Solid Tumors), safety, and tolerability were assessed in this population. A total of 65 patients received sagopilone at either 16 mg/m(2) (N = 39) or 22 mg/m(2) (N = 26). Patients received a median of two cycles of sagopilone. Among the 65 patients who were evaluable for efficacy, there were three confirmed tumor responses over both treatment arms; however, the primary target of the study was not reached. The main treatment-related adverse events were sensory neuropathy (81.5%) and fatigue (44.6%). There were no deaths related to the study drug. Sagopilone was moderately tolerated in both treatment arms and showed limited activity in heavily pre-treated patients with MBC. C1 [Morrow, Phuong K.; Hortobagyi, Gabriel N.] Univ Texas MD Anderson Canc Ctr, Dept Breast Med Oncol, Houston, TX 77030 USA. [Divers, Stephen] Genesis Canc Ctr, Hot Springs, AR USA. [Provencher, Louise] CHA Laval Univ, Ctr Malad Sein Deschenes Fabia, Quebec City, PQ, Canada. [Luoh, Shiuh-Wen] Oregon Hlth & Sci Univ, Portland, OR 97201 USA. [Luoh, Shiuh-Wen] Portland VA Med Ctr, Portland, OR USA. [Petrella, Teresa M.] Sunnybrook Hlth Sci Ctr, Toronto, ON M4N 3M5, Canada. [Giurescu, Marius; Schmelter, Thomas] Bayer Schering Pharma AG, Berlin, Germany. [Wang, Yao] Bayer HealthCare Pharmaceut, Wayne, NJ USA. [Vahdat, Linda T.] Weill Cornell Med Coll, New York, NY USA. RP Morrow, PK (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Breast Med Oncol, 1515 Holcombe,Box 1354, Houston, TX 77030 USA. EM pmorrow@mdanderson.org OI Vahdat, Linda/0000-0002-3522-7382 FU Bayer HealthCare Pharmaceuticals; Glaxo Smith Kline; Pfizer; Novartis FX The authors would like to thank Tanya Chaudry, Ph.D., at Complete HealthVizion for assistance in the preparation and revision of the draft manuscript, based on detailed discussion and feedback from the authors. Editorial assistance was supported by a grant from Bayer HealthCare Pharmaceuticals. We would also like to thank all investigators who participated in this study.; Dr. Shiuh-Wen Luoh receives research support from Glaxo Smith Kline and serves as an Institute PA for clinical trials sponsored by Glaxo Smith Kline. Dr. Teresa M. Petrella is a consultant for Glaxo Smith Kline, Merck, and Pfizer. She has received research funds from Pfizer. Dr. Marius Giurescu is an employee of Bayer Schering Pharma. Dr. Thomas Schmelter is an employee of Bayer Schering Pharma. Dr. Yao Wang is an employee of Bayer HealthCare Pharmaceuticals and owns company stocks in Bayer HealthCare Pharmaceuticals Dr. Gabriel N. Hortobagyi is a consultant for Novartis, Merck and Sanofi Aventis; he has received research support from Novartis. Dr. Linda T. Vahdat is a consultant for Bayer. NR 22 TC 10 Z9 10 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD OCT PY 2010 VL 123 IS 3 BP 837 EP 842 DI 10.1007/s10549-010-1102-x PG 6 WC Oncology SC Oncology GA 651BQ UT WOS:000281900000023 PM 20697802 ER PT J AU Lehmann, N Joshi, GP Dirkmann, D Weiss, M Gulur, P Peters, J Eikermann, M AF Lehmann, N. Joshi, G. P. Dirkmann, D. Weiss, M. Gulur, P. Peters, J. Eikermann, M. TI Development and longitudinal validation of the overall benefit of analgesia score: a simple multi-dimensional quality assessment instrument SO BRITISH JOURNAL OF ANAESTHESIA LA English DT Article DE adverse effects; analgesics; opioids; clinical trials; pain measurement; pain; postoperative; patient satisfaction ID POSTOPERATIVE PAIN MANAGEMENT; INVENTORY; VALIDITY; SURGERY AB The goal of this study was to develop and validate the overall benefit of analgesic score (OBAS), which assesses pain intensity and the opioid-related adverse effects. The score was developed and validated in four trials (n=1470 patients). Data from randomized trial I were used to develop the OBAS (factor analysis). Data from randomized trial II were used to compare the resolution of rofecoxib's analgesic effects between OBAS and pain scores. Randomized trial III (spine surgery) was conducted to evaluate prospectively the reliability of the OBAS and to compare its resolution of analgesic treatment with the opioid-related symptom distress scale (OR-SDS) and the modified brief pain inventory short form (m-BPI-sf). Trial IV was conducted to evaluate in patients with a moderate-to-high level of postoperative pain (after major abdominal surgery) the relation of OBAS and pain scores for patients' satisfaction with analgesic therapy. The seven-item OBAS yielded a higher resolution of analgesic treatment effects than pain scores, the OR-SDS and m-BPI-sf. The OBAS has a fair inter-rater reliability (concordance correlation of 0.71 c) and is more sensitive (P=0.03) in indicating the delivery of opioid boluses than the dedicated OR-SDS. The OBAS, but not pain scores at rest or pain scores during movement, explained significant variance in patients' satisfaction with postoperative pain therapy. The OBAS is a simple, multi-dimensional quality assessment instrument to measure patients' benefit from postoperative pain therapy. Opioid symptom distress, pain relief, and patients' satisfaction are combined in a reliable and valid tool. C1 [Dirkmann, D.; Weiss, M.; Peters, J.; Eikermann, M.] Univ Klinikum Essen, Univ Duisburg Essen, Klin Anasthesiol & Intensivmed, Essen, Germany. [Lehmann, N.] Univ Klinikum Essen, Univ Duisburg Essen, Inst Med Informat Biometrie & Epidemiol, Essen, Germany. [Joshi, G. P.] Univ Texas Dallas, SW Med Ctr, Dallas, TX USA. [Gulur, P.; Eikermann, M.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Gulur, P.; Eikermann, M.] Harvard Univ, Sch Med, Boston, MA USA. RP Eikermann, M (reprint author), Univ Klinikum Essen, Univ Duisburg Essen, Klin Anasthesiol & Intensivmed, Essen, Germany. EM meikermann@rics.bwh.harvard.edu FU Klinik fur Anasthesiologie und Intensivmedizin, Universitatsklinikum Essen, Essen, Germany; Massachusetts General Hospital in Boston, MA, USA FX This work was supported financially by the Klinik fur Anasthesiologie und Intensivmedizin, Universitatsklinikum Essen, Essen, Germany, and the Massachusetts General Hospital in Boston, MA, USA. The OBAS was not designed to make fortunes from inventions of measurement tools. Accordingly, we decided not to have patents or copyrights involved. NR 25 TC 10 Z9 10 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0007-0912 J9 BRIT J ANAESTH JI Br. J. Anaesth. PD OCT PY 2010 VL 105 IS 4 BP 511 EP 518 DI 10.1093/bja/aeq186 PG 8 WC Anesthesiology SC Anesthesiology GA 651TR UT WOS:000281950500018 PM 20693179 ER PT J AU Advani, RH Chen, HY Habermann, TM Morrison, VA Weller, EA Fisher, RI Peterson, BA Gascoyne, RD Horning, SJ AF Advani, Ranjana H. Chen, Haiyan Habermann, Thomas M. Morrison, Vicki A. Weller, Edie A. Fisher, Richard I. Peterson, Bruce A. Gascoyne, Randy D. Horning, Sandra J. CA Eastern Cooperative Oncology Grp Canc Leukemia Grp B SW Oncology Grp TI Comparison of conventional prognostic indices in patients older than 60 years with diffuse large B-cell lymphoma treated with R-CHOP in the US Intergroup Study (ECOG 4494, CALGB 9793): consideration of age greater than 70 years in an elderly prognostic index (E-IPI) SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article; Proceedings Paper CT 48th Annual Meeting of the American-Society-of-Hematology CY DEC, 2006 CL Atlanta, GA SP Amer Soc Hematol DE immunochemotherapy; prognostic; elderly; non-Hodgkin lymphoma; CHOP ID NON-HODGKINS-LYMPHOMA; CHEMOTHERAPY PLUS RITUXIMAB; RANDOMIZED CONTROLLED-TRIAL; MODEL; COMORBIDITY; EXPRESSION; SURVIVAL; IMPACT; CANCER AB To assess if immunochemotherapy influenced the prognostic value of IPI in elderly diffuse large B-cell lymphoma (DLBCL) patients, we evaluated the performance of the standard International Prognostic Index (IPI) and following modifications: age adjusted (AA)-IPI, revised (R)-IPI, and an elderly IPI with age cut-off 70 years (E-IPI) in patients > 60 years treated with RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone). In 267 patients, by IPI/AA-IPI 60% were high-intermediate, 53% high and 12% low risk. With R-IPI, 60% were poor risk and none very good risk. Using E-IPI, 45% were high-intermediate/high risk and 27% low risk. No differences in outcome were seen in the low/low-intermediate groups with IPI/AA-IPI. For E-IPI, failure-free survival (FFS) and overall survival (OS) were significantly different for low/low-intermediate groups. No differences were detected in the four indices with model fit/discrimination measures; however, E-IPI ranked highest. For elderly R-CHOP treated patients, distribution of IPI/AA-IPI skewed toward high/high-intermediate risk with no differences in FFS/OS between low/low-intermediate risk. In contrast, with E-IPI, more are classified as low risk with significant differences in FFS/OS for low-intermediate compared to low risk. The R-IPI does not identify a very good risk group, thus minimizing its utility in this population. The prognostic discrimination provided by the E-IPI for low and low-intermediate elderly DLBCL patients needs validation by other datasets. C1 [Advani, Ranjana H.] Stanford Univ, Med Ctr, Stanford, CA 94305 USA. [Chen, Haiyan] Univ Maryland, Sch Med, Baltimore, MD 21201 USA. [Habermann, Thomas M.] Mayo Clin, Rochester, MN USA. [Morrison, Vicki A.; Peterson, Bruce A.; Canc Leukemia Grp B] Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA. [Weller, Edie A.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Fisher, Richard I.; SW Oncology Grp] Univ Rochester, Rochester, NY USA. [Gascoyne, Randy D.; Eastern Cooperative Oncology Grp] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. RP Advani, RH (reprint author), Stanford Univ, Med Ctr, 875 Blake Wilbur Dr,Suite CC 2338, Stanford, CA 94305 USA. EM radvani@stanford.edu FU NCI NIH HHS [CA66636, CA11083, CA13650, CA16450, CA21115, CA23318, CA32291, N01 CA035431, U10 CA011083, U10 CA013650, U10 CA021115, U10 CA023318, U10 CA032291, U10 CA035431, U10 CA066636, U24 CA114737, UG1 CA189808] NR 31 TC 41 Z9 43 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD OCT PY 2010 VL 151 IS 2 BP 143 EP 151 DI 10.1111/j.1365-2141.2010.08331.x PG 9 WC Hematology SC Hematology GA 656XN UT WOS:000282374500003 PM 20735398 ER PT J AU Camargo, CA Ingham, T Wickens, K Thadhani, RI Silvers, KM Epton, MJ Town, GI Espinola, JA Crane, J AF Camargo, Carlos A., Jr. Ingham, Tristram Wickens, Kristin Thadhani, Ravi I. Silvers, Karen M. Epton, Michael J. Town, G. Ian Espinola, Janice A. Crane, Julian CA New Zealand Asthma Allergy Cohort TI Vitamin D status of newborns in New Zealand SO BRITISH JOURNAL OF NUTRITION LA English DT Article DE Vitamin D; 25-Hydroxyvitamin D; Newborns; Pregnancy; New Zealand ID D DEFICIENCY; PREGNANT-WOMEN; HIGH PREVALENCE; D INSUFFICIENCY; DIETARY-INTAKE; CHILDREN; 25-HYDROXYVITAMIN-D; RISK AB Recognition of the important non-skeletal health effects of vitamin D has focused attention on the vitamin D status of individuals across the lifespan. To examine the vitamin D status of newborns, we measured serum levels of 25-hydroxyvitamin D (25(OH) D) in the cord blood of 929 apparently healthy newborns in a population-based study in New Zealand, a country at 41 degrees S latitude, with strong anti-skin cancer (sun avoidance) campaigns and without vitamin D food fortification. Randomly selected midwives in two regions recruited children. The median cord blood level of 25(OH) D was 44 nmol/l (interquartile range, 29-78 nmol/l). Overall, 19% of newborns had 25(OH) D levels <25 nmol/l and 57% had levels <50 nmol/l; only 27% had levels of 75 nmol/l or higher, which are levels associated with optimal health in older children and adults. A multivariable ordinal logistic regression model showed that the strongest determinants of low vitamin D status were winter month of birth and non-European ethnicity. Other determinants of low cord blood 25(OH) D included longer gestational age, younger maternal age and a parental history of asthma. In summary, low levels of vitamin D are common among apparently healthy New Zealand newborns, and are independently associated with several easily identified factors. Although the optimal timing and dosage of vitamin D supplementation require further study, our findings may assist future efforts to correct low levels of 25(OH) D among New Zealand mothers and their newborn children. C1 [Camargo, Carlos A., Jr.; Espinola, Janice A.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA. [Camargo, Carlos A., Jr.; Thadhani, Ravi I.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr D Receptor Activat Res, Boston, MA 02114 USA. [Ingham, Tristram; Wickens, Kristin; Crane, Julian] Univ Otago, Wellington Asthma Res Grp, Dept Med, Wellington Sch Med & Hlth Sci, Wellington, New Zealand. [Silvers, Karen M.; Epton, Michael J.] Univ Otago, Canterbury Resp Res Grp, Dept Med, Christchurch Sch Med, Christchurch, New Zealand. [Town, G. Ian] Univ Canterbury, Christchurch 1, New Zealand. RP Camargo, CA (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Emergency Med, 326 Cambridge St,Suite 410, Boston, MA 02114 USA. EM ccamargo@partners.org RI Osborne, Nicholas/N-4915-2015 OI Osborne, Nicholas/0000-0002-6700-2284 FU Health Research Council of New Zealand; David and Cassie Anderson Bequest (Wellington, New Zealand); Massachusetts General Hospital Center for D-receptor Activation Research (Boston, MA, USA) FX We thank the midwives in Wellington, Porirua and Canterbury for their assistance with recruitment, and all the families and children for their participation. The New Zealand Asthma and Allergy Cohort Study Group consisted of J. C., M. Duignan, M. J. E., D. Fishwick, P. Fitzharris, T. I., V. Irvine, R. Kelly, P. Lampshire, J. Lane, P. Leadbitter, C. MacDonald, F. McCartin, S. McLeod, A. Nicholson, P. Pattemore, K. Roff, G. Sawyer, R. Siebers, G. I. T., K. W., H. Wilson and K. Withell. This work was supported by grants from the Health Research Council of New Zealand, the David and Cassie Anderson Bequest (Wellington, New Zealand), and the Massachusetts General Hospital Center for D-receptor Activation Research (Boston, MA, USA). None of the authors has any potential conflicts of interest. The authors' contributions are as follows: C. A. C. had full access to all the data in the study, and takes responsibility for the integrity of the data and the accuracy of the data analysis. C. A. C., G. I. T. and J. C. were involved in the study concept and design. C. A. C., T. I., K. W., R. I. T., M. J. E., G. I. T. and J. C. were involved in the acquisition of data. C. A. C., T. I., K. W., K. M. S., J. A. E. and J. C. were involved in the analysis and interpretation of data. C. A. C. was involved in the preparation of the manuscript. The critical revision of the manuscript for important intellectual content was done by C. A. C., T. I., K. W., R. I. T., K. M. S., M. J. E., G. I. T., J. A. E. and J. C. C.; A. C. and J. A. E. performed the statistical analysis. C. A. C., M. J. E. and J. C. were involved in the study supervision. NR 32 TC 27 Z9 28 U1 0 U2 6 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND SN 0007-1145 J9 BRIT J NUTR JI Br. J. Nutr. PD OCT PY 2010 VL 104 IS 7 BP 1051 EP 1057 DI 10.1017/S0007114510001674 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 677SR UT WOS:000284012600016 PM 20426893 ER PT J AU Ehrenfeld, JM Funk, LM Van Schalkwyk, J Merry, AF Sandberg, WS Gawande, A AF Ehrenfeld, Jesse M. Funk, Luke M. Van Schalkwyk, Johan Merry, Alan F. Sandberg, Warren S. Gawande, Atul TI The incidence of hypoxemia during surgery: evidence from two institutions SO CANADIAN JOURNAL OF ANESTHESIA-JOURNAL CANADIEN D ANESTHESIE LA English DT Article ID SUPPLEMENTAL PERIOPERATIVE OXYGEN; INFORMATION-MANAGEMENT SYSTEMS; EARLY POSTOPERATIVE HYPOXEMIA; SURGICAL-WOUND INFECTION; PULSE OXIMETRY FAILURE; CLOSED CLAIMS ANALYSIS; ANESTHETIC MANAGEMENT; RANDOMIZED EVALUATION; INTERMITTENT HYPOXIA; SINGLE-BLIND AB Purpose The incidence of hypoxemia in patients undergoing surgery, is largely unknown and may have a clinical impact. The objective of this study was to determine the incidence of intraoperative hypoxemia in a large surgical population. Methods We performed a retrospective study of electronically recorded pulse oximetry data obtained from two large academic medical centres. All adults (age >= 16 yr) undergoing non-cardiac surgery during a three-year period at the two hospitals were included in the analysis. Our main outcome measure was the percentage of patients with episodes of hypoxemia (SpO(2) < 90) or severe hypoxemia (SpO(2) <= 85) for two minutes or longer during the intraoperative period (induction of anesthesia, surgery, and emergence). Results We evaluated 95,407 electronic anesthesia records at the two hospitals. During the intraoperative period, 6.8% of patients had a hypoxemic event, and 3.5% of patients had a severely hypoxemic event of two consecutive minutes or longer. Seventy percent of the hypoxemic episodes occurred during either induction or emergence time periods that represent 21% of the total intraoperative time. From induction to emergence, one episode of hypoxemia occurred every 28.9 hr, and one episode of severe hypoxemia occurred every 55.7 hr of intraoperative time. Conclusion Despite advances in monitoring technology, hypoxemia continues to occur commonly in the operating room and may be a serious safety concern because of its potential impact on end organ function and long-term outcomes. Further studies are needed to improve our understanding of the clinical impact of intraoperative hypoxemia and the strategies that will be most useful in minimizing its occurrence. C1 [Ehrenfeld, Jesse M.; Sandberg, Warren S.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Boston, MA 02114 USA. [Funk, Luke M.; Gawande, Atul] Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. [Funk, Luke M.; Gawande, Atul] Harvard Univ, Sch Publ Hlth, Dept Hlth Policy & Management, Boston, MA 02115 USA. [Van Schalkwyk, Johan; Merry, Alan F.] Auckland City Hosp, Dept Anaesthesia, Auckland, New Zealand. [Merry, Alan F.] Univ Auckland, Dept Anaesthesiol, Auckland 1, New Zealand. RP Ehrenfeld, JM (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, 55 Fruit St,Jackson 458, Boston, MA 02114 USA. EM jehrenfe@post.harvard.edu OI Ehrenfeld, Jesse/0000-0003-3427-0140; Sandberg, Warren/0000-0002-9246-777X; Gawande, Atul/0000-0002-1824-9176; Merry, Alan/0000-0001-7100-009X FU Department of Anesthesia, Critical Care & Pain Medicine, Massachusetts General Hospital; National Institute of Health [5T32GM007592] FX Financial support for the preparation of this manuscript was provided from department funds of the Department of Anesthesia, Critical Care & Pain Medicine, Massachusetts General Hospital and from 5T32GM007592 from the National Institute of Health. NR 59 TC 23 Z9 26 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0832-610X EI 1496-8975 J9 CAN J ANESTH JI Can. J. Anesth. PD OCT PY 2010 VL 57 IS 10 BP 888 EP 897 DI 10.1007/s12630-010-9366-5 PG 10 WC Anesthesiology SC Anesthesiology GA 654RF UT WOS:000282185000003 PM 20680710 ER PT J AU Kraybill, WG Harris, J Spiro, IJ Ettinger, DS DeLaney, TF Blum, RH Lucas, DR Harmon, DC Letson, GD Eisenberg, B AF Kraybill, William G. Harris, Jonathan Spiro, Ira J. Ettinger, David S. DeLaney, Thomas F. Blum, Ronald H. Lucas, David R. Harmon, David C. Letson, G. Douglas Eisenberg, Burton TI Long-Term Results of a Phase 2 Study of Neoadjuvant Chemotherapy and Radiotherapy in the Management of High-Risk, High-Grade, Soft Tissue Sarcomas of the Extremities and Body Wall Radiation Therapy Oncology Group Trial 9514 SO CANCER LA English DT Article DE sarcoma; neoadjuvant chemotherapy; radiation ID LIMB-SPARING SURGERY; ADJUVANT CHEMOTHERAPY; RANDOMIZED-TRIAL; POSTOPERATIVE RADIOTHERAPY; SYNOVIAL SARCOMA; ADULT PATIENTS; METAANALYSIS; SURVIVAL AB BACKGROUND: The use of neoadjuvant and adjuvant chemotherapy in soft tissue sarcomas is controversial. This is a report of long-term (>= 5 years) follow-up in patients with high-grade, high-risk soft tissue sarcomas treated with neoadjuvant chemotherapy, preoperative radiotherapy (RT), and adjuvant chemotherapy. METHODS: Patients with high-grade soft tissue sarcoma >= 8 cm in diameter of the extremities and body wall received 3 cycles of neoadjuvant chemotherapy (mesna, doxorubicin, ifosfamide, and dacarbazine) and preoperative RT (44 grays administered in split courses), and 3 cycles of postoperative chemotherapy (mesna, doxorubicin, ifosfamide, and dacarbazine). RESULTS: Sixty-four of 66 patients were analyzed. After chemotherapy and RT, 61 patients had surgery; 58 had R0 resections (5 amputations), and 3 had R1 resections. Ninety-seven percent experienced grade 3 or higher toxicity, including 3 deaths. These toxicities were short term. With a median follow-up of 7.7 years in surviving patients, the 5-year rates of locoregional failure (including amputation), and distant metastasis were 22.2% (95% confidence interval [CI], 11.8-32.6) and 28.1% (95% CI, 17.0-39.2). The most common site of metastasis was lung. Estimated 5-year rates of disease-free survival, distant disease-free survival, and overall survival were 56.1% (95% CI, 43.9-68.3), 64.1% (95% CI, 52.3-75.8), and 71.2% (95% CI, 60.0-82.5), respectively. CONCLUSIONS: Although the toxicity was significant, it was limited in its course and for the most part resolved by 1 year. The long-term outcome was better than might be expected in such high-risk tumors. Cancer 2010;116:4613-21. (C) 2010 American Cancer Society. C1 [Kraybill, William G.] Arthur G James Canc Hosp, Dept Surg, Columbus, OH USA. [Kraybill, William G.] Ohio State Univ, Richard J Solove Res Inst, Columbus, OH 43210 USA. [Kraybill, William G.] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Harris, Jonathan] Radiat Therapy Oncol Grp Stat Ctr, Dept Stat, Philadelphia, PA USA. [Spiro, Ira J.; DeLaney, Thomas F.] Massachusetts Gen Hosp, Dept Radiat Oncol, Francis H Burr Proton Therapy Ctr, Boston, MA 02114 USA. [Ettinger, David S.] Johns Hopkins Med Ctr, Dept Med Oncol, Baltimore, MD USA. [Blum, Ronald H.] Beth Israel Canc Ctr, Dept Med Oncol, New York, NY USA. [Lucas, David R.] Univ Michigan, Med Ctr, Dept Pathol, Ann Arbor, MI 48109 USA. [Letson, G. Douglas] Univ S Florida, H Lee Moffitt Canc Ctr, Dept Orthoped, Tampa, FL 33682 USA. [Eisenberg, Burton] Dartmouth Hitchcock Med Ctr, Dept Surg, Lebanon, NH 03766 USA. RP Kraybill, WG (reprint author), Ohio State Univ, Div Surg Oncol, Med Ctr, N904,Doan Hall,410 W 10th Ave, Columbus, OH 43210 USA. EM william.kraybill@osumc.edu FU NCI [RTOG U10 CA21661, CCOP U10 CA37422, Stat U10 CA32115] FX Supported by RTOG U10 CA21661, CCOP U10 CA37422, and Stat U10 CA32115 grants from the NCI. The contents are the sole responsibility of the authors and do not necessarily represent the official views of the NCI. Dr. Ettinger has acted as a consultant for AstraZeneca, Bristol-Myers Squibb, Celgene, Eli Lilly & Co., Eisai, Genentech, GlaxoSmithKline, Imclone, Merck, Novartis, Pfizer, and Sanofi-Aventis. Dr. Letson has acted as a consultant for Stryker. Dr. Eisenberg has served on the Novartis advisory board. NR 37 TC 32 Z9 35 U1 2 U2 4 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0008-543X EI 1097-0142 J9 CANCER-AM CANCER SOC JI Cancer PD OCT 1 PY 2010 VL 116 IS 19 BP 4613 EP 4621 DI 10.1002/cncr.25350 PG 9 WC Oncology SC Oncology GA 655QA UT WOS:000282263300022 PM 20572040 ER PT J AU Broniscer, A Baker, JN Baker, SJ Chi, SN Geyer, JR Morris, EB Gajjar, A AF Broniscer, Alberto Baker, Justin N. Baker, Suzanne J. Chi, Susan N. Geyer, J. Russell Morris, E. Brannon Gajjar, Amar TI Prospective Collection of Tissue Samples at Autopsy in Children With Diffuse Intrinsic Pontine Glioma SO CANCER LA English DT Article DE autopsy; brain; children; diffuse intrinsic pontine glioma; molecular studies ID PEDIATRIC BRAIN-STEM; CANCER; MUTATIONS; SUBTYPES; THERAPY; DEATH; EGFR AB BACKGROUND: Brain tissue obtained at autopsy has been used in research for non-oncologic disorders. However, to the best of the authors' knowledge, this tool has never been systematically used in large investigational studies for cancer. A prospective, multicenter study was conducted to assess the feasibility of tissue collection at autopsy and its suitability for molecular analyses in children with diffuse intrinsic pontine glioma. METHODS: Tumor tissue was collected at the time of diagnosis, if clinically indicated, or at autopsy. Normal brain tissue was also collected at autopsy. The integrity of DNA and RNA was evaluated in all samples. Logistic data regarding autopsies were recorded. The feasibility of tissue collection at autopsy was assessed for patients treated at a single institution over a 43-month period. RESULTS: Tumor samples were collected at the time of diagnosis (n = 3) or at autopsy (n = 38) at 29 centers across the United States; samples were obtained at diagnosis and autopsy in 2 cases. The median interval from death to autopsy was 7.7 hours. DNA and RNA with minimal or partial degradation, which were suitable for genome-wide analysis, were obtained from 100% and 63% of tumor samples, respectively. At the coordinating institution, approximately 40% of parents consented to autopsy and 40% declined. During the study period, 12 autopsies were performed on patients who did not receive therapy at the coordinating center. CONCLUSIONS: Multicenter, biological studies based on tissue obtained at autopsy appear to be feasible in children with brain cancer. The current experience established a new paradigm for brain tissue collection, which may increase the potential for research studies in patients with cancer. Cancer 2010;116:4632-7. (C) 2010 American Cancer Society. C1 [Broniscer, Alberto; Morris, E. Brannon; Gajjar, Amar] St Jude Childrens Hosp, Dept Oncol, Memphis, TN 38105 USA. [Broniscer, Alberto; Gajjar, Amar] Univ Tennessee, Ctr Hlth Sci, Dept Pediat, Memphis, TN 38163 USA. [Baker, Justin N.] St Jude Childrens Hosp, Dept Pediat Med, Memphis, TN 38105 USA. [Baker, Suzanne J.] St Jude Childrens Hosp, Dept Dev Neurobiol, Memphis, TN 38105 USA. [Chi, Susan N.] Childrens Hosp, Dana Farber Canc Inst, Dept Pediat, Boston, MA 02115 USA. [Geyer, J. Russell] Seattle Childrens Hosp, Dept Pediat Hematol Oncol, Seattle, WA USA. RP Broniscer, A (reprint author), St Jude Childrens Hosp, Dept Oncol, 262 Danny Thomas Pl,Mail Stop 260, Memphis, TN 38105 USA. EM alberto.broniscer@stjude.org OI Broniscer, Alberto/0000-0001-9646-0463 FU US National Institutes of Health [P30 CA21765, P01 CA096832]; Tyler's Treehouse Foundation; Cure Starts Now Foundation; Smiles for Sophie Forever Foundation; National Brain Tumor Society's Sydney Schlobohm Chair of Research; Noyes Brain Tumor Foundation, Musicians Against Childhood Cancer (MACC); American Lebanese Syrian Associated Charities (ALSAC) FX Supported by the Cancer Center Support [CORE] Grant P30 CA21765 and Grant P01 CA096832 from the US National Institutes of Health, the Tyler's Treehouse Foundation, The Cure Starts Now Foundation, the Smiles for Sophie Forever Foundation, the National Brain Tumor Society's Sydney Schlobohm Chair of Research, the Noyes Brain Tumor Foundation, Musicians Against Childhood Cancer (MACC), and the American Lebanese Syrian Associated Charities (ALSAC). NR 28 TC 34 Z9 34 U1 0 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD OCT 1 PY 2010 VL 116 IS 19 BP 4632 EP 4637 DI 10.1002/cncr.25405 PG 6 WC Oncology SC Oncology GA 655QA UT WOS:000282263300024 PM 20589749 ER PT J AU Wright, AA Mack, JW Kritek, PA Balboni, TA Massaro, AF Matulonis, UA Block, SD Prigerson, HG AF Wright, Alexi A. Mack, Jennifer W. Kritek, Patricia A. Balboni, Tracy A. Massaro, Anthony F. Matulonis, Ursula A. Block, Susan D. Prigerson, Holly G. TI Influence of Patients' Preferences and Treatment Site on Cancer Patients' End-of-Life Care SO CANCER LA English DT Article DE treatment preferences; cancer; terminal illness; end-of-life care; communication; prognosis; intensive care; treatment site; hospice ID SERIOUSLY ILL PATIENTS; MEDICARE BENEFICIARIES; ASSOCIATIONS; INTENSITY; MORTALITY; OUTCOMES; DEATH AB BACKGROUND: Research suggests that patients' end-of-life (EOL) care is determined primarily by the medical resources available, and not by patient preferences. The authors examined whether patients' desire for life-extending therapy was associated with their EOL care. METHODS: Coping with Cancer is a multisite, prospective, longitudinal study of patients with advanced cancer. Three hundred one patients were interviewed at baseline and followed until death, a median of 4.5 months later. Multivariate analyses examined the influence of patients' preferences and treatment site on whether patients received intensive care or hospice services in the final week of life. RESULTS: Eighty-three of 301 patients (27.6%) with advanced cancer wanted life-extending therapy at baseline. Patients who understood that their disease was terminal or who reported having EOL discussions with their physicians were less likely to want life-extending care compared with others (23.4% vs 42.6% and 20.7% vs 44.4%, respectively; P <= .003). Patients who were treated at Yale Cancer Center received more intensive care (odds ratio [OR], 3.14; 95% confidence interval [CI], 1.16-8.47) and less hospice services (OR, 0.52; 95% CI, 0.29-0.92) compared with patients who were treated at Parkland Hospital. However, in multivariate analyses that controlled for confounding influences, patients who preferred life-extending care were more likely to receive intensive care (adjusted OR [AOR], 2.91; 95% CI, 1.09-7.72) and were less likely to receive hospice services (AOR, 0.45; 95% CI, 0.26-0.78). Treatment site was not identified as a significant predictor of EOL care. CONCLUSIONS: The treatment preferences of patients with advanced cancer may play a more important role in determining the intensity of medical care received at the EOL than previously recognized. Future research is needed to determine the mechanisms by which patients' preferences for care and treatment site interact to influence EOL care. Cancer 2010; 116: 4656-63. (C) 2010 American Cancer Society. C1 [Wright, Alexi A.; Matulonis, Ursula A.; Prigerson, Holly G.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Wright, Alexi A.; Balboni, Tracy A.; Block, Susan D.; Prigerson, Holly G.] Dana Farber Canc Inst, Ctr Psychooncol & Palliat Care Res, Boston, MA 02115 USA. [Wright, Alexi A.; Mack, Jennifer W.; Kritek, Patricia A.; Balboni, Tracy A.; Massaro, Anthony F.; Matulonis, Ursula A.; Block, Susan D.; Prigerson, Holly G.] Harvard Univ, Sch Med, Boston, MA USA. [Wright, Alexi A.; Mack, Jennifer W.; Balboni, Tracy A.; Prigerson, Holly G.] Dana Farber Canc Inst, Ctr Outcomes & Policy Res, Boston, MA 02115 USA. [Mack, Jennifer W.] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA. [Kritek, Patricia A.; Massaro, Anthony F.] Brigham & Womens Hosp, Combined Program Pulm & Crit Care, Boston, MA 02115 USA. [Balboni, Tracy A.] Dana Farber Canc Inst, Dept Radiat Oncol, Boston, MA 02115 USA. [Block, Susan D.; Prigerson, Holly G.] Harvard Univ, Sch Med, Ctr Palliat Care, Boston, MA USA. [Block, Susan D.; Prigerson, Holly G.] Brigham & Womens Hosp, Dept Psychiat, Boston, MA 02115 USA. RP Wright, AA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Smith 333,44 Binney St, Boston, MA 02115 USA. EM alexi_wright@dfci.harvard.edu FU National Institute of Mental Health [MH63892]; National Cancer Institute [CA106370, CA092203]; American Society of Clinical Oncology/Susan G. Komen; Center for Psycho-Oncology and Palliative Care Research; Dana-Farber Cancer Institute FX This research was supported in part by grant MH63892 from the National Institute of Mental Health, grant CA106370 from the National Cancer Institute to Dr. Prigerson, grant CA092203 from the National Cancer Institutes' Program in Cancer Outcomes Research Training to Dr. Wright, an American Society of Clinical Oncology/Susan G. Komen for the Cure Young Investigator Award to Dr. Wright, and the Center for Psycho-Oncology and Palliative Care Research, Dana-Farber Cancer Institute. None of the authors have a relationship with any entities that have a financial interest in this topic. NR 21 TC 34 Z9 35 U1 0 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD OCT 1 PY 2010 VL 116 IS 19 BP 4656 EP 4663 DI 10.1002/cncr.25217 PG 8 WC Oncology SC Oncology GA 655QA UT WOS:000282263300027 PM 20572030 ER PT J AU Smith, SM Ford, JS Rakowski, W Moskowitz, CS Diller, L Hudson, MM Mertens, AC Stanton, AL Henderson, TO Leisenring, WM Robison, LL Oeffinger, KC AF Smith, Stephanie M. Ford, Jennifer S. Rakowski, William Moskowitz, Chaya S. Diller, Lisa Hudson, Melissa M. Mertens, Ann C. Stanton, Annette L. Henderson, Tara O. Leisenring, Wendy M. Robison, Leslie L. Oeffinger, Kevin C. TI Inconsistent mammography perceptions and practices among women at risk of breast cancer following a pediatric malignancy: a report from the Childhood Cancer Survivor Study SO CANCER CAUSES & CONTROL LA English DT Article DE Cancer survivorship; Late effects; Screening; Transtheoretical model; Stages of adoption ID ACUTE LYMPHOBLASTIC-LEUKEMIA; HEALTH LOCUS; HODGKINS-DISEASE; DECISIONAL BALANCE; SCREENING BEHAVIOR; CONTROL BELIEFS; FAMILY-HISTORY; 2ND CANCERS; RADIATION; INTERVENTIONS AB Women treated with chest radiation for a pediatric cancer have low mammography screening rates despite their high risk for breast cancer. This study characterized the relationship between perceptions of mammography and screening practices. A cross-sectional survey was administered to 523 women in North America who were treated with chest radiation before 21 years of age. Women with inconsistent mammography perceptions and practices were identified using the Pros and Cons of Mammography for perceptions and Transtheoretical Model stages of adoption for prior and intended screening practices. Classification and regression tree (CART) analysis was used to identify barriers to and facilitators of screening among women with positive and negative perceptions. Nearly one-third of the cohort had inconsistent perceptions and practices: 37.4% had positive perceptions and were not having mammograms; 27.6% had negative/neutral perceptions and were having mammograms. Regardless of perceptions, a recent physician's recommendation for mammography, age a parts per thousand yen 40, and interest in routine health care were universally associated with mammography practices. For women with positive perceptions and a physician's recommendation, barriers to screening included high acceptance coping, low active-planning coping, and high internal health locus of control. For women with negative perceptions, acknowledging the importance of asymptomatic screening was associated with mammography. C1 [Oeffinger, Kevin C.] Mem Sloan Kettering Canc Ctr, Dept Pediat, New York, NY 10021 USA. [Oeffinger, Kevin C.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA. [Smith, Stephanie M.; Ford, Jennifer S.] Mem Sloan Kettering Canc Ctr, Dept Pediat, New York, NY 10065 USA. [Ford, Jennifer S.] Mem Sloan Kettering Canc Ctr, Dept Psychiat & Behav Sci, New York, NY 10065 USA. [Rakowski, William] Brown Univ, Dept Community Hlth, Providence, RI 02912 USA. [Moskowitz, Chaya S.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10065 USA. [Diller, Lisa] Childrens Hosp, Dana Farber Canc Inst, Boston, MA 02115 USA. [Hudson, Melissa M.; Robison, Leslie L.] St Jude Childrens Res Hosp, Memphis, TN 38105 USA. [Mertens, Ann C.] Emory Univ, Atlanta, GA 30322 USA. [Stanton, Annette L.] Univ Calif Los Angeles, Los Angeles, CA 90095 USA. [Henderson, Tara O.] Univ Chicago, Chicago, IL 60637 USA. [Leisenring, Wendy M.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. [Smith, Stephanie M.] Stanford Univ, Sch Med, Stanford, CA 94305 USA. RP Oeffinger, KC (reprint author), Mem Sloan Kettering Canc Ctr, Dept Pediat, 1275 York Ave, New York, NY 10021 USA. EM oeffingk@mskcc.org FU National Cancer Institute/Department of Health and Human Services [R21-CA-106972]; Department of Health and Human Services [U24-CA-55727]; Children's Cancer Research Fund; American Lebanese Syrian Associated Charities (ALSAC) FX This work was supported by Grant R21-CA-106972 (K. C. Oeffinger, Principal Investigator) from the National Cancer Institute/Department of Health and Human Services and the Centers for Disease Control and Prevention, Grant U24-CA-55727 (L. L. Robison, Principal Investigator) from the Department of Health and Human Services, funding to the University of Minnesota from the Children's Cancer Research Fund and funding to St. Jude Children's Research Hospital from the American Lebanese Syrian Associated Charities (ALSAC). NR 52 TC 5 Z9 5 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 EI 1573-7225 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD OCT PY 2010 VL 21 IS 10 BP 1585 EP 1595 DI 10.1007/s10552-010-9587-5 PG 11 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 651NQ UT WOS:000281934800006 PM 20506037 ER PT J AU Chan, JA Zhu, AX Stuart, K Bhargava, P Earle, CC Clark, JW Casey, C Regan, E Kulke, MH AF Chan, Jennifer A. Zhu, Andrew X. Stuart, Keith Bhargava, Pankaj Earle, Craig C. Clark, Jeffrey W. Casey, Carolyn Regan, Eileen Kulke, Matthew H. TI Phase II study of pemetrexed in patients with advanced neuroendocrine tumors SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE Pemetrexed; Neuroendocrine tumor; Carcinoid tumor; Pancreatic neuroendocrine tumor ID MALIGNANT PLEURAL MESOTHELIOMA; ENDOTHELIAL GROWTH-FACTOR; CARCINOID-TUMOR; THYMIDYLATE SYNTHASE; FLUOROURACIL; STREPTOZOCIN; DOXORUBICIN; ANTIFOLATE; LY231514; CHEMOTHERAPY AB Purpose In some reports, 5-fluorouracil has been associated with modest activity in patients with neuroendocrine tumors. Pemetrexed is a multitargeted antifolate with activity in tumor types not significantly responsive to other antifolates. We evaluated the efficacy of pemetrexed in a phase II study of patients with advanced neuroendocrine tumors. Methods Patients with metastatic neuroendocrine tumors (excluding small-cell carcinoma) were treated with pemetrexed administered intravenously at a dose of 500 mg/m(2) every 21 days. To reduce potential toxicity, patients also received folic acid, vitamin B12 supplementation, and peri-infusional treatment with dexamethasone. Patients were followed for response, toxicity, and survival. Results The study was designed with a total accrual goal of 32 patients. Due to lack of radiographic responses in patients during the study period, accrual was terminated at 17. However, one patient achieved a delayed partial response following discontinuation of pemetrexed. Ten patients were evaluable for biochemical response; five (50%) experienced > 50% decrease in plasma chromogranin A. Among the 17 patients, 5 (29%) discontinued therapy due to treatment-related toxicity. The median overall survival was 12.1 months. Conclusion Pemetrexed does not appear to have significant antitumor activity in patients with advanced neuroendocrine tumors. The limited antitumor activity and potential toxicity associated with pemetrexed mirrors experience with the majority of other cytotoxic agents in patients with neuroendocrine tumors. Investigation of novel, molecularly targeted agents may offer more promise in this disease. C1 [Chan, Jennifer A.; Bhargava, Pankaj; Earle, Craig C.; Casey, Carolyn; Regan, Eileen; Kulke, Matthew H.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. [Zhu, Andrew X.; Clark, Jeffrey W.] Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. [Stuart, Keith] Beth Israel Deaconess Med Ctr, Div Hematol Oncol, Boston, MA 02215 USA. RP Chan, JA (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Dana 1220,44 Binney St, Boston, MA 02115 USA. EM jang@partners.org FU Saul and Gitta Kurlat Fund for Neuroendocrine Tumor Research; NCI [CA093401, P50 CA127003] FX Support for this study was provided by the Stephen and Caroline Kaufer Fund for Neuroendocrine Tumor Research. Pemetrexed was supplied by Lilly, Inc. The authors acknowledge additional support from the Saul and Gitta Kurlat Fund for Neuroendocrine Tumor Research, and NCI grants CA093401 (MHK) and P50 CA127003 (DF/HCC SPORE in Gastrointestinal Cancer). NR 27 TC 3 Z9 3 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0344-5704 EI 1432-0843 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD OCT PY 2010 VL 66 IS 5 BP 961 EP 968 DI 10.1007/s00280-010-1248-6 PG 8 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 638VH UT WOS:000280924900017 PM 20130879 ER PT J AU Kumar, M Yigit, M Dai, GP Moore, A Medarova, Z AF Kumar, Mohanraja Yigit, Mehmet Dai, Guangping Moore, Anna Medarova, Zdravka TI Image-Guided Breast Tumor Therapy Using a Small Interfering RNA Nanodrug SO CANCER RESEARCH LA English DT Article ID IN-VIVO; SIRNA DELIVERY; NONINVASIVE DETECTION; CANCER; NANOPARTICLES; THERAPEUTICS; ANTIGEN; SYSTEM; TARGET; CELLS AB Iron oxide nanoparticles offer a feasible tool for combined imaging and delivery of small interfering RNA (siRNA) to tumors, stimulating active interest in exploring different imaging and delivery platforms suitable for detection by a variety of modalities. In this study, we describe the synthesis and testing of a tumor-targeted nanodrug (MN-EPPT-siBIRC5) that is designed to specifically shuttle siRNA to human breast tumors. The nanodrug binds the tumor-specific antigen uMUC-1, which is found in >90% of human breast adenocarcinomas. MN-EPPT-siBIRC5 consists of superparamagnetic iron oxide nanoparticles [for magnetic resonance imaging (MRI)], the dye Cy5.5 (for near-IR optical imaging), peptides (EPPT) that specifically target uMUC-1, and a synthetic siRNA that targets the tumor-specific antiapoptotic gene BIRC5. Nanodrug uptake by human breast adenocarcinoma cells resulted in a significant downregulation of BIRC5. Following i.v. delivery into subcutaneous mouse models of breast cancer, the nanodrug showed a preferential tumor uptake, which could be visualized by MRI and near-IR optical imaging. Furthermore, MRI could be used to quantitatively monitor nanodrug bioavailability in the tumor tissue throughout the course of treatment. Intravenous injection of the agent once a week over 2 weeks resulted in the induction of considerable levels of necrosis and apoptosis in the tumors, translating into a significant decrease in tumor growth rate. Our strategy permits the simultaneous tumor-specific delivery of siRNA to tumors and the imaging of the delivery process. More generally, it illustrates the potential to apply this approach to many human cancer studies, including for basic tumor biology and therapy. Cancer Res; 70(19); 7553-61. (C) 2010 AACR. C1 [Kumar, Mohanraja; Yigit, Mehmet; Dai, Guangping; Moore, Anna; Medarova, Zdravka] Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Radiol, Mol Imaging Lab,MGH HST Athinoula A Martinos Ctr, Boston, MA USA. RP Medarova, Z (reprint author), Harvard Univ, Sch Med, Massachusetts Gen Hosp,Dept Radiol, Mol Imaging Lab,MGH MIT HMS Athinoula A Martinos, Bldg 75,13th St, Charlestown, MA 02129 USA. EM zmedarova@partners.org FU NIH [R00CA129070] FX NIH grant R00CA129070 (Z. Medarova). NR 34 TC 92 Z9 96 U1 2 U2 23 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 1 PY 2010 VL 70 IS 19 BP 7553 EP 7561 DI 10.1158/0008-5472.CAN-10-2070 PG 9 WC Oncology SC Oncology GA 660MM UT WOS:000282647700019 PM 20702603 ER PT J AU Whitehurst, AW Xie, Y Purinton, SC Cappell, KM Swanik, JT Larson, B Girard, L Schorge, JO White, MA AF Whitehurst, Angelique W. Xie, Yang Purinton, Scott C. Cappell, Kathryn M. Swanik, Jackie T. Larson, Brittany Girard, Luc Schorge, John O. White, Michael A. TI Tumor Antigen Acrosin Binding Protein Normalizes Mitotic Spindle Function to Promote Cancer Cell Proliferation SO CANCER RESEARCH LA English DT Article ID PROBE LEVEL DATA; LUNG-CANCER; EXTRA CENTROSOMES; OVARIAN-CANCER; PHASE-II; NUMA; ANEUPLOIDY; IDENTIFICATION; CARBOPLATIN; INSTABILITY AB Cancer cells manage to divide in the context of gross chromosomal abnormalities. These abnormalities can promote bypass of normal restraints on cell proliferation but at a cost of mitotic vulnerabilities that can be attacked by chemotherapy. Determining how cancer cells balance these issues may permit chemotherapeutic sensitivity to be leveraged more efficiently. From a pan-genomic small interfering RNA screen for modifiers of chemoresponsiveness, we identified the tumor antigen acrosin binding protein (ACRBP)/OY-TES-1 as a specifier of paclitaxel resistance. ACRBP expression is normally restricted to the testes but is detected in a wide variety of cancers, including most ovarian cancers. We found that ACRBP is both necessary and sufficient for paclitaxel resistance in ovarian cancer cell lines and ovarian tumor explants. Moreover, high ACRBP expression correlated with reduced survival time and faster relapse among ovarian cancer patients. We identified the mitotic spindle protein NuMA as an ACRBP-interacting protein that could account for the effects of ACRBP on paclitaxel sensitivity. In cancer cells, ACRBP restricted a NuMA-dependent abrogation of a mitotic spindle assembly that is otherwise pathologic. As a consequence, ACRBP depletion resulted in mitotic errors and reduced proliferative fitness that could be rescued by NuMA codepletion. We propose that the codependent relationship of ACRBP and NuMA in cancer cells reflects their passage through a selection bottleneck during tumor evolution, one which requires the acquisition of traits that normalize mitotic perturbations that originally drove the plasticity of a preneoplastic genome. The molecular definition of such traits as defined by the ACRBP-NuMA complex may represent conceptually ideal intervention targets based on the wide therapeutic windows they may offer. Cancer Res; 70(19); 7652-61. (C) 2010 AACR. C1 [Whitehurst, Angelique W.; Cappell, Kathryn M.; Swanik, Jackie T.; Larson, Brittany] Univ N Carolina, Dept Pharmacol, Chapel Hill, NC 27599 USA. [Schorge, John O.] Massachusetts Gen Hosp, Div Gynecol Oncol, Boston, MA 02114 USA. [White, Michael A.] Univ Texas SW Med Ctr Dallas, Dept Cell Biol, Dallas, TX 75390 USA. [Purinton, Scott C.] Univ Texas SW Med Ctr Dallas, Dept Obstet & Gynecol, Dallas, TX 75390 USA. [Xie, Yang] Univ Texas SW Med Ctr Dallas, Div Biostat, Dept & Clin Sci, Dallas, TX 75390 USA. [Girard, Luc] Univ Texas SW Med Ctr Dallas, Hamon Ctr Therapeut Oncol Res, Dallas, TX 75390 USA. RP Whitehurst, AW (reprint author), Univ N Carolina, Dept Pharmacol, 4093 Genet Med, Chapel Hill, NC 27599 USA. EM awhit1@med.unc.edu; Michael.white@UTSouthwestern.edu FU Robert Welch Foundation [I-1414]; National Cancer Institute [CA71443, CA128926, CA071341-14]; American Cancer Society [PF-07-120-01-GMC]; [UL1 RR024982] FX Robert Welch Foundation grant I-1414 and National Cancer Institute grants CA71443 (M. A. White) and CA128926 (A.W. Whitehurst). Y. Xie was supported by UL1 RR024982, K.M. Cappell was supported by National Cancer Institute training grant CA071341-14, and A. W. Whitehurst was supported in part by the American Cancer Society grant PF-07-120-01-GMC. NR 36 TC 21 Z9 23 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD OCT 1 PY 2010 VL 70 IS 19 BP 7652 EP 7661 DI 10.1158/0008-5472.CAN-10-0840 PG 10 WC Oncology SC Oncology GA 660MM UT WOS:000282647700029 PM 20876808 ER PT J AU Tsai, TT AF Tsai, Thomas T. TI No Free Lunch: Transradial Access in Patients on Coumadin SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Editorial Material ID PERCUTANEOUS CORONARY INTERVENTION C1 [Tsai, Thomas T.] Univ Colorado, Denver VA Med Ctr, Denver, CO 80202 USA. RP Tsai, TT (reprint author), 1055 Clermont St, Denver, CO 80220 USA. EM thomas.tsai@ucdenver.edu NR 7 TC 0 Z9 0 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD OCT 1 PY 2010 VL 76 IS 4 BP 500 EP 501 DI 10.1002/ccd.22785 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 658FN UT WOS:000282476000008 PM 20882652 ER PT J AU Suh, WM Witzke, CF Palacios, IF AF Suh, William M. Witzke, Christian F. Palacios, Igor F. TI Suicide Left Ventricle Following Transcatheter Aortic Valve Implantation SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Article DE aortic stenosis; transcatheter aortic valve implantation; left ventricular outflow obstruction; suicide left ventricle ID SEPTAL HYPERTROPHY; STENOSIS; REPLACEMENT AB In some patients with aortic stenosis, dynamic intraventricular gradients like those seen in hypertrophic obstructive cardiomyopathy may develop secondary to left ventricular hypertrophy from chronic pressure overload. With the advent of transcatheter aortic valve implantation, many patients with aortic stenosis and advanced age who formerly would be considered "too high risk" for aortic valve replacement are getting treatment for their aortic stenosis. This case highlights the hemodynamic aberrations that can occur with TAVI leading to a cautionary note regarding implementation of this rapidly emerging technique in patients with left ventricles that may be at risk for suicide left ventricle. (C) 2010 Wiley-Liss, Inc. C1 [Palacios, Igor F.] Harvard Univ, Massachusetts Gen Hosp, Div Cardiol, Sch Med, Boston, MA 02114 USA. RP Palacios, IF (reprint author), Harvard Univ, Massachusetts Gen Hosp, Div Cardiol, Sch Med, 55 Fruit St,GRB800, Boston, MA 02114 USA. EM ipalacios@partners.org NR 12 TC 17 Z9 17 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD OCT 1 PY 2010 VL 76 IS 4 BP 616 EP 620 DI 10.1002/ccd.22609 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 658FN UT WOS:000282476000030 PM 20506145 ER PT J AU Nathan, DG AF Nathan, David G. TI A Life-Long Quest to Understand and Treat Genetic Blood Disorders SO CELL LA English DT Editorial Material ID ALPHA THALASSEMIA; DELETION; DIAGNOSIS; MALARIA; ANEMIA; FORM C1 [Nathan, David G.] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Nathan, David G.] Dana Farber Canc Inst, Boston, MA 02115 USA. [Nathan, David G.] Childrens Hosp, Boston, MA 02115 USA. RP Nathan, DG (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. EM david_nathan@dfci.harvard.edu NR 15 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0092-8674 J9 CELL JI Cell PD OCT 1 PY 2010 VL 143 IS 1 BP 17 EP 20 DI 10.1016/j.cell.2010.09.015 PG 4 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 656UC UT WOS:000282362000007 PM 20887886 ER PT J AU Kutuk, O Letai, A AF Kutuk, O. Letai, A. TI Displacement of Bim by Bmf and Puma rather than increase in Bim level mediates paclitaxel-induced apoptosis in breast cancer cells SO CELL DEATH AND DIFFERENTIATION LA English DT Article DE apoptosis; Bim; Bmf; Puma; BH3; paclitaxel ID BCL-2 FAMILY-MEMBERS; MITOCHONDRIAL APOPTOSIS; CYTOCHROME-C; PROAPOPTOTIC ACTIVITY; MOTOR COMPLEX; BAX; DEATH; ACTIVATION; PROTEIN; P53 AB Taxanes exert their antitumor effect through stabilizing microtubule dynamics and initiating G2/M arrest in cancer cells followed by apoptotic cell death. However, the signaling pathways that connect paclitaxel-induced microtubule perturbation to mitochondrial outer membrane permeabilization and cytochrome c release are not well characterized. Here, we show that in breast cancer cells, paclitaxel induces a novel displacement mechanism: prodeath BH3-only proteins Bmf and Puma competitively displace prodeath BH3-only protein Bim from antiapoptotic proteins to activate Bax and Bak and commit the cell to apoptotic death. Bim and either Puma or Bmf are required for paclitaxel toxicity. Although prior mechanisms of apoptosis induced by taxol have focused on changes in Bim levels, we find that an increase is not required for paclitaxel killing of breast cancer cells. Rather, competitive displacement of Bim from antiapoptotic proteins is the important step committing the cell to death. This novel mechanism suggests the potential usage of novel therapies targeted at altering BH3-only protein heterodimerization. Cell Death and Differentiation (2010) 17, 1624-1635; doi:10.1038/cdd.2010.41; published online 30 April 2010 C1 [Kutuk, O.; Letai, A.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. RP Letai, A (reprint author), Dana Farber Canc Inst, Dept Med Oncol, Dana 530B,44 Binney St, Boston, MA 02115 USA. EM anthony_letai@dfci.harvard.edu FU NIH [R01 CA129974]; Terri Brodeur Breast Cancer Foundation FX This work was supported by NIH grant R01 CA129974. OK gratefully acknowledges support from the Terri Brodeur Breast Cancer Foundation. AL is a Leukemia and Lymphoma Society Scholar. NR 33 TC 39 Z9 41 U1 0 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1350-9047 EI 1476-5403 J9 CELL DEATH DIFFER JI Cell Death Differ. PD OCT PY 2010 VL 17 IS 10 BP 1624 EP 1635 DI 10.1038/cdd.2010.41 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 649CQ UT WOS:000281745200010 PM 20431602 ER PT J AU Wardak, C Vanduffel, W Orban, GA AF Wardak, Claire Vanduffel, Wim Orban, Guy A. TI Searching for a Salient Target Involves Frontal Regions SO CEREBRAL CORTEX LA English DT Article DE bottom-up; fMRI; monkey; top-down; visual search ID LATERAL INTRAPARIETAL AREA; MONKEY PREFRONTAL CORTEX; SELECTIVE VISUAL-ATTENTION; POSTERIOR PARIETAL CORTEX; EYE FIELD; SPATIAL ATTENTION; TOP-DOWN; NEURONAL-ACTIVITY; NEURAL MECHANISMS; CEREBRAL-CORTEX AB Searching for an object in a complex visual scene involves selection mechanisms. Generally, it is assumed that efficient "pop-out" search involves mainly bottom-up processing, whereas inefficient search requires pronounced top-down control over visual processing. We used functional magnetic resonance imaging in behaving monkeys to explore the functional network involved in efficient visual search. As a pop-out target automatically attracts spatial attention, we attempted to determine the regions involved in feature selection independently of the spatial allocation of attention. Therefore, monkeys were trained to perform a search task in which they had to covertly detect the presence of a salient target among distractor objects. Three tasks were used to control, as much as possible, for the spatial allocation of attention. These control tasks were matched with the search task for visual input and manual responses. Pop-out search, when compared with the control tasks, activated 3 frontal regions: frontal eye field, area 45, and a posterior portion of area 46, in addition to small activation sites in lateral intraparietal area and inferotemporal area TE. Our results show that efficient search involves frontal regions as much as visual regions and in particular that ventral prefrontal area 45 is involved in top-down control during efficient search. C1 [Wardak, Claire; Vanduffel, Wim; Orban, Guy A.] Katholieke Univ Leuven, Sch Med, Lab Neuro Psychofysiol, B-3000 Louvain, Belgium. [Vanduffel, Wim] Massachusetts Gen Hosp, Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA 02129 USA. [Vanduffel, Wim] Harvard Univ, Dept Radiol, Sch Med, Charlestown, MA 02129 USA. RP Vanduffel, W (reprint author), Katholieke Univ Leuven, Sch Med, Lab Neuro Psychofysiol, Campus Gasthuisberg, B-3000 Louvain, Belgium. EM wim@nmr.mgh.harvard.edu RI Wardak, Claire/P-6222-2016 FU Human Frontiers Science Program (HFSPO); GSKE; IUAP [6/29, EF/05/014]; FWO [G151.04, G.0.622.08]; NSF [BCS-0745436]; Fyssen Foundation FX Human Frontiers Science Program (HFSPO), GSKE, IUAP 6/29, EF/05/014, FWO G151.04, and G.0.622.08, NSF grant BCS-0745436, and Fyssen Foundation (C.W.). NR 80 TC 26 Z9 26 U1 1 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD OCT PY 2010 VL 20 IS 10 BP 2464 EP 2477 DI 10.1093/cercor/bhp315 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 648SX UT WOS:000281715500018 PM 20100901 ER PT J AU Grander, W Dunser, M Stollentwerk, B Siebert, U Dengg, C Koller, B Eller, P Tilg, H AF Grander, Wilhelm Duenser, Martin Stollentwerk, Bjoern Siebert, Uwe Dengg, Clemens Koller, Bernhard Eller, Patricia Tilg, Herbert TI C-Reactive Protein Levels and Post-ICU Mortality in Nonsurgical Intensive Care Patients SO CHEST LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; CRITICALLY-ILL PATIENTS; LONG-TERM SURVIVAL; ORGAN FAILURE; ISCHEMIC-STROKE; INFLAMMATION; SEPSIS; DISEASE; ATHEROSCLEROSIS; DETERMINANTS AB Background: There are no data on the association between acute inflammation during critical illness and long-term mortality in ICU patients. Methods: Nonsurgical patients with an ICU length of stay >24 h surviving until ICU discharge were included into this prospective, observational, follow-up study. Demographics, chronic diseases, admission diagnosis, the Simplified Acute Physiology Score (SAPS) II, length of ICU stay, maximum C-reactive protein (CRP) levels during the ICU stay (CRPmax), and CRP levels at ICU discharge (CRPdis) were documented. After a follow-up time of 1.88 +/- 1.16 years (range, 0.5-4 years), the survival status was determined. Results: Seven hundred sixty-five patients were enrolled into the study protocol. One hundred fifty-eight patients (20.7%) died within 0.62 +/- 0.88 years after ICU discharge. Cumulative survival rates differed between patients grouped into the CRPmax and CRPdis quartiles. Patients in the first and second CRPmax quartiles had better cumulative survival rates than those in higher CRPmax quartiles (all P < .001). Patients in the first CRPdis quartile had better cumulative survival rates than those in higher CRPdis quartiles (all P < .001). Using adjusted Cox proportional hazards models, both CRPmax and CRPdis were independently associated with post-ICU mortality (both P < .001). Furthermore, the number of chronic diseases (P < .001), age (P < .001), and the SAPS II (P = .03) were associated with post-ICU mortality in both Cox models. Conclusions: CRP levels during critical illness seem independently associated with post-ICU survival in nonsurgical ICU patients. Future research focusing on the association between acute systemic inflammation and post-ICU outcome is warranted in order to improve long-term survival of critically ill patients. CHEST 2010; 138(4):856-862 C1 [Grander, Wilhelm; Dengg, Clemens; Koller, Bernhard; Eller, Patricia; Tilg, Herbert] Acad Teaching Hosp Hall In Tirol, Dept Intens Care Med, Hall In Tirol, Austria. [Duenser, Martin] Univ Bern, Inselspital, Dept Intens Care Med, CH-3010 Bern, Switzerland. [Stollentwerk, Bjoern; Siebert, Uwe] Univ Hlth Sci Med Informat & Technol, Dept Publ Hlth Med Decis Making & Hlth Technol As, Hall In Tirol, Austria. [Siebert, Uwe] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA. [Siebert, Uwe] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. RP Grander, W (reprint author), Acad Teaching Hosp Hall In Tirol, Dept Intens Care Med, Hall In Tirol, Austria. EM Wilhelm.Grander@bkh-hall.or.at RI Stollenwerk, Bjorn/G-5408-2013 NR 31 TC 18 Z9 18 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD OCT PY 2010 VL 138 IS 4 BP 856 EP 862 DI 10.1378/chest.09-1677 PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 664YQ UT WOS:000283000500019 PM 20173056 ER PT J AU Matthay, MA Thompson, BT Read, EJ McKenna, DH Liu, KD Calfee, CS Lee, JW AF Matthay, Michael A. Thompson, B. Taylor Read, Elizabeth J. McKenna, David H., Jr. Liu, Kathleen D. Calfee, Carolyn S. Lee, Jae Woo TI Therapeutic Potential of Mesenchymal Stem Cells for Severe Acute Lung Injury SO CHEST LA English DT Article ID DEAD-SPACE FRACTION; BONE-MARROW; MYOCARDIAL-INFARCTION; PULMONARY-ARTERY; CLINICAL-TRIAL; STROMAL CELLS; MICE; PREDICTORS; MORTALITY; PREVENTION AB Preclinical studies indicate that allogeneic human mesenchymal stein cells (MSC) may be useful for the treatment of several clinical disorders, including sepsis, acute renal failure, acute myocardial infarction, and more recently, acute lung injury (ALI). This article provides a brief review of the biologic qualities of MSC that make them suitable for the treatment of human diseases, as well as the experimental data that provide support for their potential efficacy for critically ill patients with acute respiratory failure from ALI. The article then discusses which patients with ALI might be the best candidates for cell-based therapy and provides a template for the regulatory and practical steps that will be required to test allogeneic human MSC in patients with severe ALI. There is a dual focus on how to design trials for testing both safety and efficacy. CHEST 2010;138(4):965-972 C1 [Matthay, Michael A.; Liu, Kathleen D.; Calfee, Carolyn S.; Lee, Jae Woo] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. [Matthay, Michael A.; Liu, Kathleen D.; Calfee, Carolyn S.; Lee, Jae Woo] Univ Calif San Francisco, Dept Anesthesiol, San Francisco, CA 94143 USA. [Matthay, Michael A.; Liu, Kathleen D.; Calfee, Carolyn S.; Lee, Jae Woo] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA 94143 USA. [Read, Elizabeth J.] Blood Syst Res Inst, San Francisco, CA USA. [McKenna, David H., Jr.] Univ Minnesota, Dept Mol & Cellular Therapeut, St Paul, MN 55108 USA. [Thompson, B. Taylor] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA. RP Matthay, MA (reprint author), Univ Calif San Francisco, Dept Med, 505 Parnassus Ave,M-917, San Francisco, CA 94143 USA. EM michael.matthay@ucsf.edu FU National Heart, Blood, and Lung Institute (NHBLI) [R37 HL51856, R01 HL51854, HL093026, HL090833, FAMRI, R37HL51856, N01HB37164]; Eli Lilly; National Institutes for Health and BioE, Saint Paul, MN FX This study was supported by the National Heart, Blood, and Lung Institute (NHBLI) [NHBLI Grants R37 HL51856 and R01 HL51854] (Dr Matthay); [NHBLI Grant HL093026] (Dr Lee); [NHBLI Grants HL090833 and FAMRI] (Dr Calfee); [NHBLI Grant R37HL51856] (Dr Thompson); and [NHBLI Grant N01HB37164] (Dr McKenna).; The authors have reported to CHEST the following conflicts of interest: Dr Thompson receives NHLBI funding to serve as the Medical Director of the Clinical Coordinating Center for the ARDS Clinical Trials Network. Dr Thompson is also a paid consultant to Eli Lilly, where he serves as the co-principal investigator for the PROWESS-SHOCK trial of rh-A PC for severe sepsis. Dr McKenna has received research funding through National Institutes for Health and BioE, Saint Paul, MN. Dos Matthay, Read, Liu, Calfee, and Lee have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article. NR 44 TC 77 Z9 86 U1 1 U2 9 PU AMER COLL CHEST PHYSICIANS PI GLENVIEW PA 2595 PATRIOT BLVD, GLENVIEW, IL 60026 USA SN 0012-3692 J9 CHEST JI Chest PD OCT PY 2010 VL 138 IS 4 BP 965 EP 972 DI 10.1378/chest.10-0518 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 664YQ UT WOS:000283000500034 PM 20923800 ER PT J AU Singer, DE Fang, MC Go, AS AF Singer, Daniel E. Fang, Margaret C. Go, Alan S. TI CHA(2)DS(2)-VASc Risk Scheme Not Ready for Clinical Use SO CHEST LA English DT Letter ID EURO HEART SURVEY; ATRIAL-FIBRILLATION C1 [Singer, Daniel E.] Massachusetts Gen Hosp, Clin Epidemiol Unit, Div Gen Med, Boston, MA 02114 USA. [Fang, Margaret C.; Go, Alan S.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Go, Alan S.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Go, Alan S.] Kaiser Permanente No Calif, Div Res, Oakland, CA USA. RP Singer, DE (reprint author), Massachusetts Gen Hosp, Clin Epidemiol Unit, Div Gen Med, S50-9, Boston, MA 02114 USA. EM dsinger@partners.org NR 3 TC 4 Z9 4 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD OCT PY 2010 VL 138 IS 4 BP 1020 EP 1020 DI 10.1378/chest.10-0875 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 664YQ UT WOS:000283000500043 PM 20923808 ER PT J AU Macdonald, A Danielson, CK Resnick, HS Saunders, BE Kilpatrick, DG AF Macdonald, Alexandra Danielson, Carla Kmett Resnick, Heidi S. Saunders, Benjamin E. Kilpatrick, Dean G. TI PTSD and comorbid disorders in a representative sample of adolescents: The risk associated with multiple exposures to potentially traumatic events SO CHILD ABUSE & NEGLECT LA English DT Article DE Multiple trauma; Adolescent; PTSD; Substance use; Depression ID POSTTRAUMATIC-STRESS-DISORDER; ADULT RETROSPECTIVE REPORTS; NATIONAL-SURVEY; SUBSTANCE-ABUSE; CHILDHOOD VICTIMIZATION; VIOLENCE EXPOSURE; DEPRESSION; YOUTH; RECOLLECTIONS; EXPERIENCES C1 [Macdonald, Alexandra; Danielson, Carla Kmett; Resnick, Heidi S.; Saunders, Benjamin E.; Kilpatrick, Dean G.] Med Univ S Carolina, Dept Psychiat & Behav Sci, Natl Crime Victims Res & Treatment Ctr, Charleston, SC 29425 USA. RP Macdonald, A (reprint author), VA Boston Healthcare Syst, Natl Ctr PTSD, 150 S Huntington Ave, Jamaica Plain, MA 02130 USA. NR 35 TC 20 Z9 20 U1 3 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2134 J9 CHILD ABUSE NEGLECT JI Child Abuse Negl. PD OCT PY 2010 VL 34 IS 10 BP 773 EP 783 DI 10.1016/j.chiabu.2010.03.006 PG 11 WC Family Studies; Psychology, Social; Social Work SC Family Studies; Psychology; Social Work GA 673YF UT WOS:000283699400007 PM 20869115 ER PT J AU Preuss, M Konig, IR Thompson, JR Erdmann, J Absher, D Assimes, TL Blankenberg, S Boerwinkle, E Chen, L Cupples, LA Hall, AS Halperin, E Hengstenberg, C Holm, H Laaksonen, R Li, MY Marz, W McPherson, R Musunuru, K Nelson, CP Burnett, MS Epstein, SE O'Donnell, CJ Quertermous, T Rader, DJ Roberts, R Schillert, A Stefansson, K Stewart, AFR Thorleifsson, G Voight, BF Wells, GA Ziegler, A Kathiresan, S Reilly, MP Samani, NJ Schunkert, H AF Preuss, Michael Koenig, Inke R. Thompson, John R. Erdmann, Jeanette Absher, Devin Assimes, Themistocles L. Blankenberg, Stefan Boerwinkle, Eric Chen, Li Cupples, L. Adrienne Hall, Alistair S. Halperin, Eran Hengstenberg, Christian Holm, Hilma Laaksonen, Reijo Li, Mingyao Maerz, Winfried McPherson, Ruth Musunuru, Kiran Nelson, Christopher P. Burnett, Mary Susan Epstein, Stephen E. O'Donnell, Christopher J. Quertermous, Thomas Rader, Daniel J. Roberts, Robert Schillert, Arne Stefansson, Kari Stewart, Alexandre F. R. Thorleifsson, Gudmar Voight, Benjamin F. Wells, George A. Ziegler, Andreas Kathiresan, Sekar Reilly, Muredach P. Samani, Nilesh J. Schunkert, Heribert CA CARDIoGRAM Consortium TI Design of the Coronary ARtery DIsease Genome-Wide Replication And Meta-Analysis (CARDIoGRAM) Study A Genome-Wide Association Meta-analysis Involving More Than 22 000 Cases and 60 000 Controls SO CIRCULATION-CARDIOVASCULAR GENETICS LA English DT Article DE coronary artery disease; myocardial infarction; meta-analysis; genetics ID MYOCARDIAL-INFARCTION; SUSCEPTIBILITY LOCUS; VARIANT; ATHEROSCLEROSIS; HEART; 9P21; RISK AB Background-Recent genome-wide association studies (GWAS) of myocardial infarction (MI) and other forms of coronary artery disease (CAD) have led to the discovery of at least 13 genetic loci. In addition to the effect size, power to detect associations is largely driven by sample size. Therefore, to maximize the chance of finding novel susceptibility loci for CAD and MI, the Coronary ARtery DIsease Genome-wide Replication And Meta-analysis (CARDIoGRAM) consortium was formed. Methods and Results-CARDIoGRAM combines data from all published and several unpublished GWAS in individuals with European ancestry; includes >22 000 cases with CAD, MI, or both and >60 000 controls; and unifies samples from the Atherosclerotic Disease VAscular functioN and genetiC Epidemiology study, CADomics, Cohorts for Heart and Aging Research in Genomic Epidemiology, deCODE, the German Myocardial Infarction Family Studies I, II, and III, Ludwigshafen Risk and Cardiovascular Heath Study/AtheroRemo, MedStar, Myocardial Infarction Genetics Consortium, Ottawa Heart Genomics Study, PennCath, and the Wellcome Trust Case Control Consortium. Genotyping was carried out on Affymetrix or Illumina platforms followed by imputation of genotypes in most studies. On average, 2.2 million single nucleotide polymorphisms were generated per study. The results from each study are combined using meta-analysis. As proof of principle, we meta-analyzed risk variants at 9p21 and found that rs1333049 confers a 29% increase in risk for MI per copy (P=2x10(-20)). Conclusion-CARDIoGRAM is poised to contribute to our understanding of the role of common genetic variation on risk for CAD and MI. (Circ Cardiovasc Genet. 2010;3:475-483.) C1 [Assimes, Themistocles L.; Quertermous, Thomas] Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA. [Blankenberg, Stefan] Johannes Gutenberg Univ Mainz, Med Klin & Poliklin, Mainz, Germany. [Boerwinkle, Eric] Univ Texas Houston, Hlth Sci Ctr, Ctr Human Genet, Houston, TX USA. [Boerwinkle, Eric] Inst Mol Med, Houston, TX USA. [Chen, Li; McPherson, Ruth; Roberts, Robert; Stewart, Alexandre F. R.] Univ Ottawa, John & Jennifer Ruddy Canadian Cardiovasc Gen Ctr, Ottawa, ON, Canada. Boston Univ, Dept Biostat & Epidemiol, Boston, MA 02215 USA. [O'Donnell, Christopher J.] NHLBI, Framingham, MA USA. [Hall, Alistair S.] Univ Leeds, LIGHT Res Inst, Fac Med & Hlth, Leeds, W Yorkshire, England. [Halperin, Eran] Tel Aviv Univ, Blavatnik Sch Comp Sci, IL-69978 Tel Aviv, Israel. [Halperin, Eran] Tel Aviv Univ, Dept Mol Microbiol & Biotechnol, IL-69978 Tel Aviv, Israel. [Halperin, Eran] Int Comp Sci Inst, Berkeley, CA 94704 USA. [Hengstenberg, Christian] Univ Regensburg, Klin & Poliklin Innere Med 2, Regensburg, Germany. [Laaksonen, Reijo] Tampere Univ Hosp, Ctr Sci, Tampere, Finland. [Li, Mingyao] Univ Penn, Philadelphia, PA 19104 USA. [Maerz, Winfried] Synlab Ctr, Lab Diagnost Heidelberg, Heidelberg, Germany. [Maerz, Winfried] Med Univ Graz, Inst Clin Med, Graz, Austria. [Maerz, Winfried] Med Univ Graz, Chem Lab Diagnost, Graz, Austria. [Maerz, Winfried] Univ Heidelberg, Inst Publ Hlth Social & Prevent Med, Fac Med Mannheim, Heidelberg, Germany. [Musunuru, Kiran; Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiac Unit, Boston, MA 02114 USA. [Musunuru, Kiran; Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA. [Musunuru, Kiran; Voight, Benjamin F.; Kathiresan, Sekar] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA. [Voight, Benjamin F.; Kathiresan, Sekar] MIT, Program Med & Populat Genet, Cambridge, MA 02139 USA. [Musunuru, Kiran; Voight, Benjamin F.; Kathiresan, Sekar] MIT, Broad Inst Harvard, Cambridge, MA 02139 USA. [Burnett, Mary Susan; Epstein, Stephen E.] Washington Hosp Ctr, Cardiovasc Res Inst, MedStar Res Inst, Washington, DC 20010 USA. [O'Donnell, Christopher J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. [Rader, Daniel J.; Reilly, Muredach P.] Univ Penn, Sch Med, Inst Translat Med & Therapeut, Philadelphia, PA 19104 USA. [Rader, Daniel J.; Reilly, Muredach P.] Univ Penn, Cardiovasc Inst, Philadelphia, PA 19104 USA. [Voight, Benjamin F.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA. Univ Leicester, Dept Cardiovasc Sci, Glenfield Hosp, Leicester, Leics, England. RP Schunkert, H (reprint author), Univ Lubeck, Med Klin 2, Ratzeburger Allee 160, D-23538 Lubeck, Germany. EM njs@le.ac.uk; heribert.schunkert@uk-sh.de RI Voight, Benjamin/F-1775-2011; Stewart, Alexandre/A-5677-2011; Laaksonen, Reijo/D-6323-2014; Konig, Inke/A-4544-2009; Erdmann, Jeanette/A-4417-2009; Erdmann, Jeanette/P-7513-2014; OI Cupples, L. Adrienne/0000-0003-0273-7965; Stewart, Alexandre/0000-0003-2673-9164; Erdmann, Jeanette/0000-0002-4486-6231; Ziegler, Andreas/0000-0002-8386-5397 FU Reynold's Foundation; National Heart, Lung, and Blood Institute (NHLBI) [HL087647]; Boehringer Ingelheim; PHILIPS Medical Systems; Government of Rheinland-Pfalz; Johannes-Gutenberg University of Mainz; Fondation de France, the French Ministry of Research; Institut National de la Sante et de la Recherche Medicale; National Institutes of Health (NIH) NHLBI [R01HL089650-02]; Deutsche Forschungsgemeinschaft; German Federal Ministry of Education and Research (BMBF); German National Genome Research Network; European Union (EU) [LSHM-CT-2006-037593, LSHM-CT-2004-503485, HEALTH-F2-2008-201668]; German Federal Ministry of Education and Research; Sanofi/Aventis; Roche; Dade Behring/Siemens; AstraZeneca; US NIH; NHLBI; Broad Institute Center for Genotyping and Analysis; National Center for Research Resources [U54 RR020278]; Cardiovascular Institute of the University of Pennsylvania; MedStar Research Institute; Washington Hospital Center; GlaxoSmithKline; University of Pennsylvania School of Medicine; Canadian Institutes of Health Research (CIHR) [MOP82810, MOP172605, MOP77682]; Canadian Funds for Innovation (CFI) [11966]; Heart and Stroke Foundation of Ontario [NA6001]; Wellcome Trust; BHF; UK Medical Research Council; Leicester National Institute of Health Research Biomedical Research Unit in Cardiovascular Disease; NGFNplus; BMBF; NIH/National Human Genome Research Institute (NHGRI); NIH/NHLBI; National Cancer Institute Division of Cancer Epidemiology and Genetics; Heart & Stroke Funds Ontario; CFI; Cystic Fibrosis Foundation; Cancer Immunology and Hematology Branch; Institute for Biomedical Sciences, Academia Sinica, Taipei, Taiwan; Academia Sinica; Pfizer; CIHR; [R01HG004517] FX The ADVANCE study was supported by a grant from the Reynold's Foundation and National Heart, Lung, and Blood Institute (NHLBI) grant HL087647. Genetic analyses of CADomics were supported by a research grant from Boehringer Ingelheim. Recruitment and analysis of the CADomics cohort was supported by grants from Boehringer Ingelheim and PHILIPS Medical Systems; by the Government of Rheinland-Pfalz in the context of the "Stiftung Rheinland-Pfalz fur Innovation"; by the research program "Wissen schafft Zukunft"; by the Johannes-Gutenberg University of Mainz in the context of the "Schwerpunkt Vaskulare Pravention" and the "MAIFOR grant 2001"; and by grants from the Fondation de France, the French Ministry of Research, and the Institut National de la Sante et de la Recherche Medicale.; The deCODE CAD/MI Study was sponsored by National Institutes of Health (NIH) NHLBI grant R01HL089650-02. The GerMIFS I-III (KORA) were supported by the Deutsche Forschungsgemeinschaft and the German Federal Ministry of Education and Research (BMBF) in the context of the German National Genome Research Network (NGFN-2 and NGFN-plus) and the European Union (EU)-funded integrated project Cardiogenics (LSHM-CT-2006-037593). The KORA research platform was initiated and financed by the GSF-National Research Centre for Environment and Health, which is funded by the German Federal Ministry of Education and Research and of the State of Bavaria. LURIC has received funding from the EU framework 6-funded Integrated Project "Bloodomics" (LSHM-CT-2004-503485); from the EU framework 7-funded Integrated Project AtheroRemo (HEALTH-F2-2008-201668); and from Sanofi/Aventis, Roche, Dade Behring/Siemens, and AstraZeneca. The MIGen study was funded by the US NIH and NHLBI's STAMPEED genomics research program, and genotyping was partially funded by The Broad Institute Center for Genotyping and Analysis, which is supported by grant U54 RR020278 from the National Center for Research Resources. Recruitment of PennCATH was supported by the Cardiovascular Institute of the University of Pennsylvania. Recruitment of the MedStar sample was supported in part by the MedStar Research Institute and the Washington Hospital Center and a research grant from GlaxoSmithKline. Genotyping of PennCATH and MedStar was performed at the Center for Applied Genomics at the Children's Hospital of Philadelphia and supported by GlaxoSmithKline through an Alternate Drug Discovery Initiative research alliance award (to Drs Reilly and Rader) with the University of Pennsylvania School of Medicine. The OHGS was supported by Canadian Institutes of Health Research (CIHR) #MOP82810 (to Dr Roberts), Canadian Funds for Innovation (CFI) #11966 (to Dr Roberts), Heart and Stroke Foundation of Ontario #NA6001 (to Dr McPherson), CIHR #MOP172605 (to Dr McPherson), and CIHR #MOP77682 (to Dr Stewart). The WTCCC study was funded by the Wellcome Trust. Recruitment of cases for the WTCCC study was carried out by the British Heart Foundation (BHF) Family Heart Study Research Group and supported by the BHF and the UK Medical Research Council. Dr Samani holds a chair funded by the BHF. Dr Samani also is supported by the Leicester National Institute of Health Research Biomedical Research Unit in Cardiovascular Disease.; Dr Absher reports receiving an NIH research grant for the ADVANCE study. Dr Assimes reports receiving an NIH research grant for the ADVANCE study. Dr Blankenberg reports receiving research grants from NGFNplus for Atherogenomics and from BMBF for CADomics. Dr Boerwinkle received research support from NIH/National Human Genome Research Institute (NHGRI), GWA for gene-environment interaction effects influencing CGD; NIH/NHLBI, Molecular epidemiology of essential hypertension; NIH/NHLBI, Genome-wide association for loci influencing coronary heart disease; NIH/NHLBI, Genetics of hypertension-associated treatment; NIH/NHLBI, Modeling DNA diversity in reverse cholesterol transport; NIH/NHLBI, 20-year changes in fitness and cardiovascular disease risk; NIH/NHLBI, Genetic epidemiology of sodium-lithium countertransport; NIH/National Institute of General Medical Sciences (NIGMS), Pharmacogenomic evaluation of antihypertensive responses; NIH/NIGMS, Genomic approaches to common chronic disease; NIH/NHLBI, Genes of the CYP450-derived eicosanoids in subclinical atherosclerosis; NIH/NHGRI-University of North Carolina, Chapel Hill, Genetic epidemiology of causal variants across the life course; and NIH/NHLBI, Building on GWAS for NHLBI-diseases: the CHARGE consortium. Dr Cupples reports receiving research grants from NIH/NHLBI, The Framingham Heart Study; NIH/NHLBI, Genome-wide association study of cardiac structure and function; NIH/NHLBI, Functional evaluation of GWAS loci for cardiovascular intermediate phenotypes; and NIH/NHLBI, Building on GWAS for NHLBI-diseases: the CHARGE consortium. Dr Halperin reports receiving research grants from NIH, subcontract Genome-wide association study of Non Hodgkin's lymphoma; ISF, Efficient design and analysis of disease association studies; EU, consultant AtheroRemo; NSF, Methods for sequencing based associations; BSF, Searching for causal genetic variants in breast cancer and honoraria from Scripps Institute, UCLA. Dr Halperin also reports ownership interest in Navigenics. Dr Hengstenberg reports receiving research grants for EU Cardiogenics. Dr Holm reports receiving a research grant from NIH; providing expert witness consultation for the district court of Reykjavik; serving as member of the editorial board for decodeme, a service provided by deCODE Genetics; and employment with deCODE Genetics. Dr Li reports receiving research grant R01HG004517 and other research support in the form of coinvestigator on several NIH-funded grants and receiving honoraria from National Cancer Institute Division of Cancer Epidemiology and Genetics. Dr McPherson reports receiving research grants from Heart & Stroke Funds Ontario, CIHR, and CFI. Dr Rader reports receiving research grant support from GlaxoSmithKline. Dr Roberts reports receiving research grants from the Cystic Fibrosis Foundation, NIH, and Cancer Immunology and Hematology Branch; membership on the speakers bureau for AstraZeneca; receiving honoraria from Several; and serving as consultant/advisory board member for Celera. Dr Stewart reports receiving research grant support from CIHR, Genome-wide scan to identify coronary artery disease genes, and CIHR, Genetic basis of salt-sensitive hypertension in humans; other research support from CFI: Infrastructure support; and honoraria from the Institute for Biomedical Sciences, Academia Sinica, Taipei, Taiwan. Dr Thorleifsson is an employee of deCODE Genetics.; Dr Thorsteinsdottir reports receiving research grants from NIH and EU; serving as an expert witness for a US trial; having stock options at deCODE Genetics; and havng employment with deCODE Genetics. Dr Kathiresan reports receiving research grants from Pfizer, Discovery of type 2 diabetes genes, and Alnylam, Function of new lipid genes, and serving as consultant/advisory board member for DAIICHI SANKYO Merck. Dr Reilly reports receiving research grant support from GlaxoSmithKline. Dr Schunkert reports receiving research grants from the EU, project Cardiogenics; NGFN, project Atherogenomics; and CADnet BMBF. M. Preuss, L. Chen, and Drs Knig, Thompson, Erdmann, Hall, Laaksonen, Murz, Musunuru, Nelson, Burnett, Epstein, O'Donnell, Quertermous, Schillert, Stefansson, Voight, Wells, Ziegler, and Samani have no conflicts to disclose.; Genotyping of PennCATH and MedStar was supported by GlaxoSmithKline. Dawn M. Waterworth, Max C. Walker, and Vincent Mooser are employees of GlaxoSmithKline. PennCath/MedStar investigators acknowledge the support of Eliot Ohlstein, Dan Burns and Allen Roses at GlaxoSmithKline. NR 20 TC 89 Z9 92 U1 1 U2 11 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1942-325X J9 CIRC-CARDIOVASC GENE JI Circ.-Cardiovasc. Genet. PD OCT PY 2010 VL 3 IS 5 BP 475 EP U186 DI 10.1161/CIRCGENETICS.109.899443 PG 31 WC Cardiac & Cardiovascular Systems; Genetics & Heredity SC Cardiovascular System & Cardiology; Genetics & Heredity GA 666ZX UT WOS:000283163100012 PM 20923989 ER PT J AU Stevens, LM Khairy, P Agnihotri, AK AF Stevens, Louis-Mathieu Khairy, Paul Agnihotri, Arvind K. TI Coronary Artery Bypass Grafting After Recent or Remote Percutaneous Coronary Intervention in the Commonwealth of Massachusetts SO CIRCULATION-CARDIOVASCULAR INTERVENTIONS LA English DT Article; Proceedings Paper CT 80th Annual Scientific Session of the American-Heart-Association CY NOV 04-07, 2007 CL Orlando, FL SP Amer Heart Assoc DE angioplasty; bypass; revascularization; epidemiological methods; follow-up studies ID ELUTING STENT IMPLANTATION; DIABETES-MELLITUS; ANGIOPLASTY PTCA; FOLLOW-UP; DISEASE; REVASCULARIZATION; OUTCOMES; SURGERY; ANGINA; IMPACT AB Background-In this study, we sought to characterize the outcomes after isolated coronary artery bypass grafting (CABG) in patients with a history of remote (>= 14 days), and recent (< 14 days), percutaneous coronary intervention (PCI). Methods and Results-Patients with PCI within 5 years of CABG were identified among 12 591 primary isolated CABG reported in the mandatory Massachusetts Adult Cardiac Surgery Database. Patients were excluded if they were out-of-state (n=1043, 8%), had undergone primary PCI for acute myocardial infarction (n=401, 3%), had a PCI-CABG interval > 5 years or unknown (n=136 and n=673, 1% and 5%). Patients with a history of remote and recent PCI were analyzed separately. Each CABG patient with PCI was matched to 3 patients without PCI using a propensity score. Outcomes were analyzed using generalized estimating equations and stratified proportional hazards models, with a mean follow-up of 4.1 +/- 1.2 years. There were 1117 CABG patients (9%) with prior PCI (n(remote) =823; n(recent) =294). In matched CABG patients with remote prior PCI, no differences were found in 30-day mortality (1.1% versus 1.5%; P=0.432), hospital morbidity (41% versus 40%; P=0.385) and overall survival (hazard ratio, [95% confidence interval] for death for prior PCI, 0.93 [0.74 to 1.18]; P=0.555). In matched CABG patients with recent prior PCI, hospital morbidity was higher (59% versus 45%; P < 0.001), but no differences were found in 30-day mortality (3.5% versus 3.1%; P=0.754) and overall survival (HR, 1.18 [0.83 to 1.69]; P=0.353). Conclusions-In patients undergoing CABG, remote prior PCI (>= 14 days) was not associated with adverse outcomes at 30 days or during long-term follow-up. (Circ Cardiovasc Interv. 2010;3:460-467.) C1 [Agnihotri, Arvind K.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiac Surg,Dept Cardiothorac Surg, Boston, MA 02114 USA. [Stevens, Louis-Mathieu] Ctr Hosp Univ Montreal, Div Cardiac Surg, Montreal, PQ, Canada. [Khairy, Paul] Montreal Heart Inst, Div Cardiol, Montreal, PQ H1T 1C8, Canada. RP Agnihotri, AK (reprint author), Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Cardiac Surg,Dept Cardiothorac Surg, 55 Fruit St,COX 630, Boston, MA 02114 USA. EM aagnihotri@partners.org RI Stevens, Louis-Mathieu/E-6453-2016 OI Stevens, Louis-Mathieu/0000-0003-3372-3419 FU Canadian Institutes of Health Research NR 25 TC 4 Z9 4 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7640 J9 CIRC-CARDIOVASC INTE JI Circ.-Cardiovasc. Interv. PD OCT PY 2010 VL 3 IS 5 BP 460 EP U112 DI 10.1161/CIRCINTERVENTIONS.109.901637 PG 15 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 666ZA UT WOS:000283160500015 PM 20736447 ER PT J AU Solis, J Levine, RA Johnson, B Guerrero, JL Handschumacher, MD Sullivan, S Lam, K Berlin, J Braithwaite, GJC Muratoglu, OK Vlahakes, GJ Hung, J AF Solis, Jorge Levine, Robert A. Johnson, Benjamin Guerrero, J. Luis Handschumacher, Mark D. Sullivan, Suzanne Lam, Kaitlyn Berlin, Jason Braithwaite, Gavin J. C. Muratoglu, Orhun K. Vlahakes, Gus J. Hung, Judy TI Polymer Injection Therapy to Reverse Remodel the Papillary Muscles Efficacy in Reducing Mitral Regurgitation in a Chronic Ischemic Model SO CIRCULATION-CARDIOVASCULAR INTERVENTIONS LA English DT Article DE mitral regurgitation; left ventricular remodeling; coronary artery disease ID POLY(VINYL ALCOHOL) HYDROGELS; 3-DIMENSIONAL ECHOCARDIOGRAPHY; MYOCARDIAL-INFARCTION; VALVE REPAIR; ANNULOPLASTY; RECONSTRUCTION; MECHANISM; SEVERITY; INSIGHTS; SYSTEM AB Background-Ischemic mitral regurgitation (MR) results from displacement of the papillary muscles caused by ischemic ventricular distortion. Progressive left ventricular (LV) remodeling has challenged therapy. Our hypothesis is that repositioning of the papillary muscles can be achieved by injection of polyvinyl-alcohol (PVA) hydrogel polymer into the myocardium in chronic MR despite advanced LV remodeling. Methods and Results-Ten sheep underwent ligation of the circumflex branches to produce chronic ischemic MR over 8 weeks. PVA was injected into the myocardium underlying the infarcted papillary muscle. Two-dimensional and 3D echocardiograms and hemodynamic data were obtained before infarct (baseline), before PVA (chronic MR), and after PVA. PVA injection significantly decreased MR from moderate to severe to trace (MR vena contracta, 5.8 +/- 1.2 to 1.8 +/- 1.3 mm; chronic MR to post-PVA stage; P=0.0003). This was associated with a decrease in infarcted papillary muscle-to-mitral annulus tethering distance (30.3 +/- 5.7 to 25.9 +/- 4.6 mm, P=0.02), tenting volume (1.8 +/- 0.7 to 1.4 +/- 0.5 mL, P=0.01), and leaflet closure area (8.8 +/- 1.3 cm(2) to 7.6 +/- 1.3 cm(2), P=0.004) from chronic MR to post-PVA stages. PVA was not associated with significant decreases in LV ejection fraction (41 +/- 3% versus 40 +/- 3%, P=NS), end-systolic elastance, tau(82 +/- 36 ms to 72 +/- 26, P=NS), or LV stiffness coefficient (0.05 +/- 0.04 to 0.03 +/- 0.01). Conclusions-PVA hydrogel injections improve coaptation and reduce remodeling in chronic MR without impairing LV systolic and diastolic function. This new approach offers a potential alternative for relieving tethering and ischemic MR by correcting papillary muscle position. (Circ Cardiovasc Interv. 2010;3:499-505.) C1 [Solis, Jorge; Levine, Robert A.; Johnson, Benjamin; Guerrero, J. Luis; Handschumacher, Mark D.; Sullivan, Suzanne; Lam, Kaitlyn; Hung, Judy] Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Boston, MA 02114 USA. [Berlin, Jason; Braithwaite, Gavin J. C.] Cambridge Polymer Inc, Boston, MA USA. [Muratoglu, Orhun K.] Massachusetts Gen Hosp, Biomat Lab, Dept Orthoped Surg, Boston, MA 02114 USA. [Vlahakes, Gus J.] Massachusetts Gen Hosp, Cardiac Surg Div, Boston, MA 02114 USA. RP Hung, J (reprint author), Massachusetts Gen Hosp, Cardiac Ultrasound Lab, Blake 256,55 Fruit St, Boston, MA 02114 USA. EM jhung@partners.org OI Braithwaite, Gavin/0000-0002-6239-0046 FU NIH/National Institute for Biomedical Imaging and Bioengineering (NIBIB) [R21 EB005294]; NIH/(National Heart Lung Blood Institute) [R01 HL092101, NHLBI R01 038176]; CIMIT [K24 HL67434, 07CVD04]; Fondation Leducq, Paris, France [07CVD04]; American Society of echocardiography; Spanish Society of Cardiology FX This work was supported in part by NIH/National Institute for Biomedical Imaging and Bioengineering (NIBIB) R21 EB005294, NIH/(National Heart Lung Blood Institute R01 HL092101 (Dr Hung), NIH/ (National Heart Lung Blood Institute) NHLBI R01 038176, CIMIT (Dr Hung) and K24 HL67434, grant 07CVD04 of Fondation Leducq, Paris, France (Dr Levine), and Echo-Investigator Award from the American Society of echocardiography (Dr Hung), and an American Society of Echocardiography Career Development Award and Spanish Society of Cardiology (postresidency grant) (Dr Solis). NR 38 TC 12 Z9 12 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7640 J9 CIRC-CARDIOVASC INTE JI Circ.-Cardiovasc. Interv. PD OCT PY 2010 VL 3 IS 5 BP 499 EP 505 DI 10.1161/CIRCINTERVENTIONS.109.850255 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 666ZA UT WOS:000283160500020 PM 20736444 ER EF